1. Last 7 days
  2. www.sciencedirect.com www.sciencedirect.com
    Virus-induced deconjugation of ISG15 dysregulates innate immunity and cellular metabolism
    20
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    sciencedirect.com/science/article/pii/S1074761326003067
  3. www.sciencedirect.com www.sciencedirect.com
    Stabilized phospholipid-topotecan prodrug particles increase vascular permeability and ultrasound-enhanced neuroblastoma delivery
    3
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    sciencedirect.com/science/article/pii/S0378517326007313
  4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Development of a human iPSC-derived corticospinal tract-on-a-chip
    1
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    pmc.ncbi.nlm.nih.gov/articles/PMC13390070/
  5. www.sciencedirect.com www.sciencedirect.com
    Lactobacillus gasseri postbiotics ameliorate age-related decline in endometrial receptivity
    14
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    sciencedirect.com/science/article/pii/S1931312826002787
  6. www.sciencedirect.com www.sciencedirect.com
    Cholesterol enhances lysosome-autophagosome fusion for better α-synuclein clearance in GBA L444P-mutated Parkinson disease
    33
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    sciencedirect.com/science/article/pii/S2211124726008788
  7. www.sciencedirect.com www.sciencedirect.com
    Neocentromeres fail to maintain DNA methylation boundaries, driving CENP-A drift, instability, and chromosome missegregation
    2
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    sciencedirect.com/science/article/pii/S221112472600848X
  8. www.sciencedirect.com www.sciencedirect.com
    A complete genome for the common marmoset
    2
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    sciencedirect.com/science/article/pii/S0092867426008159
  9. www.sciencedirect.com www.sciencedirect.com
    A complete diploid human genome benchmark for personalized genomics
    2
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    sciencedirect.com/science/article/pii/S0092867426007038
  10. www.sciencedirect.com www.sciencedirect.com
    4,4’-dimethoxychalcone induces thermosensitive impairment of SIRT3-associated mitochondrial signaling and apoptotic cell death with therapeutic potential in cancer
    7
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    sciencedirect.com/science/article/pii/S0009279726004059
  11. www.google.com www.google.com
    when is the moon not visible during the day - Google Search
    4
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    google.com/search
  12. freakonometrics.github.io freakonometrics.github.io
    Chapitre 6 — Mutualiser, segmenter – La société au prix du risque
    1
    1. Monsieur__R 09 Aug 2026
      Le price walking désigne une augmentation progressive par rapport au coût attendu, fondée sur la faible probabilité de départ du client.

      Si j'ai bien suivi, cette pratique est interdite au UK ?

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    freakonometrics.github.io/risk-priced-society/fr/chapters/chapitre-06.html
  13. www.carbonbrief.org www.carbonbrief.org
    Q&A: Does the world need ‘carbon capture and storage’ to reach net-zero? - Carbon Brief
    2
    1. mrchrisadams 09 Aug 2026
      (At the end of 2025, BP withdrew its involvement in one of the blue hydrogen facilities at the Teesside site. A data centre is planned for the site instead.) Net Zero Teesside, a gas-CCS power plant in the East Coast Cluster run by BP and Equinor, has been unsuccessfully challenged in court over its emissions savings. The challenge was based on the idea that potential upstream emissions could significantly exceed any emissions cuts from CCS use.

      Replacing blue hydrogen with a datcentre

    2. mrchrisadams 09 Aug 2026
      Between the CCC’s sixth and seventh carbon budget advice, its recommendations for power and industry CCS capacity dropped from 46MtCO2 to 41MtCO2

      Getting to 40 million tonnes by 2030 when it’s already halfway through 2026 seems implausible. Does that chart show 40million really show 40 million tonnes per year, or is it cumulative?

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    carbonbrief.org/qa-does-the-world-need-carbon-capture-and-storage-to-reach-net-zero
  14. 019f8ff9-72cd-78ff-b5bc-dca023e02b01-8080.eur-1.aiven.app 019f8ff9-72cd-78ff-b5bc-dca023e02b01-8080.eur-1.aiven.app
    Deploy on Amazon EKS
    1
    1. padmashreemp 09 Aug 2026
      If your deployment also requires STS or EKS Authentication endpoints (for example, for IRSA or EKS Pod Identity), create those separately before running the bootstrap script.

      This gives no steps, no AWS CLI command, and no link for how to actually create those endpoints.

      Atleast a reference link could be included if that makes sense from the scope of this guide

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    019f8ff9-72cd-78ff-b5bc-dca023e02b01-8080.eur-1.aiven.app/latest/migration-assistant/migration-phases/deploy/deploying-to-eks/
  15. popcar.bearblog.dev popcar.bearblog.dev
    It's not about physical vs digital games, it's about ownership
    1
    1. nafnlj 09 Aug 2026
      But if you care about these things (you clearly do since you read this far), please support the creators that are fighting against this future. Buy DRM-free stuff. Donate to an organization that preserves games & game-related content. Donate to emulator developers. Support your friendly neighbourhood indie devs. Make some noise online. We don't want physical media, we want digital ownership rights! Don't confuse the argument!

      Arguing that focusing on physical games vs digital games misses the significance of ownership rights, specifically noting that one can fully own a DRM-free digital game.

      DRM Physical Games Digital Games
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    popcar.bearblog.dev/its-about-ownership/
  16. 019f8ff9-72cd-78ff-b5bc-dca023e02b01-8080.eur-1.aiven.app 019f8ff9-72cd-78ff-b5bc-dca023e02b01-8080.eur-1.aiven.app
    Playbook: Elasticsearch 6.8 to OpenSearch 3.5 on EKS (existing VPC)
    1
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    019f8ff9-72cd-78ff-b5bc-dca023e02b01-8080.eur-1.aiven.app/latest/migration-assistant/playbook-elasticsearch-6-8-to-opensearch-3/
  17. www.youtube.com www.youtube.com
    IPIP Communication App Session 01 - 16-07-2026
    1
    1. indyweb 09 Aug 2026

      self

      online@youtube.com

      archived-transcript

      archived-video

      https://bafybeiauoba2v3e2hihuim4bc7jth2aivk53k4atka7mudo26y7oaqqnxe.ipfs.inbrowser.link/%F0%9F%97%AB/IPIP.Communication.App/session/1/@/youtube/ss360.mp4

      archived-video

      [x] (https://bafybeiauoba2v3e2hihuim4bc7jth2aivk53k4atka7mudo26y7oaqqnxe.ipfs.dweb.link/%F0%9F%97%AB/IPIP.Communication.App/session/1/@/youtube/ss360.mp4)

      local.video

      💻/thinkpad/🧊/me/📓/2026/7/1/7

      🗫/IPIP.Communication.App/session/1/@/youtube/

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    youtube.com/watch
  18. 019f8ff9-72cd-78ff-b5bc-dca023e02b01-8080.eur-1.aiven.app 019f8ff9-72cd-78ff-b5bc-dca023e02b01-8080.eur-1.aiven.app
    Migration Assistant troubleshooting
    2
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    019f8ff9-72cd-78ff-b5bc-dca023e02b01-8080.eur-1.aiven.app/latest/migration-assistant/troubleshooting/
  19. www.instagram.com www.instagram.com
    Acme Typewriters on Instagram: "This rare and extraordinary typewriter is one of the most complete surviving factory Fraktur typewriters known. Manufactured in 1985 for the “Bund für deutsche Schrift” (Association for the German Script), it combines the exceptionally rare factory Fraktur typeface with its original documentation recording delivery to the association, factory identification tag, spare Fraktur type slugs, and original carrying case—all preserved in exceptional original condition. Unlike earlier Fraktur typewriters, the Erika 127 was manufactured in 1985 and belongs to the final generation of mechanical writing machines, allowing the distinctive beauty of this historic typeface to be enjoyed with a light, fluid typing action that is both practical for extended writing and remarkably easy to master. Few typefaces are as closely associated with the cultural history of a nation as Fraktur. Developed from late medieval blackletter scripts, it became the principal printed typeface of the German-speaking world for almost four centuries. Although its official use declined during the twentieth century, Fraktur experienced a remarkable revival among typographers, calligraphers, book artists, and collectors who value its extraordinary visual richness and unmistakable historical character. Typed on paper, Fraktur produces a page that recalls fine letterpress printing more readily than conventional typescript, giving even ordinary correspondence a distinctive presence. The *Bund für deutsche Schrift* was founded to preserve and promote the traditional German scripts—Fraktur for printing and Sütterlin or Kurrent for handwriting—at a time when they had largely disappeared from everyday use. During the 1980s the association commissioned a limited number of Fraktur-equipped Erika typewriters from VEB Robotron so that members could continue producing authentic Fraktur documents using modern mechanical equipment. This typewriter is available for purchase now. You can read more about it on our website. See the link in our bio/profile. #typewriter #typewriterrevolution #typewritercollector #frakturtypewriter"
    1
    1. chrisaldrich 09 Aug 2026
      The *Bund für deutsche Schrift* was founded to preserve and promote the traditional German scripts—Fraktur for printing and Sütterlin or Kurrent for handwriting—at a time when they had largely disappeared from everyday use. During the 1980s the association commissioned a limited number of Fraktur-equipped Erika typewriters from VEB Robotron so that members could continue producing authentic Fraktur documents using modern mechanical equipment.

      https://www.instagram.com/p/DbgXamRguND/

      Fraktur typeface Erika typewriters Erika 127 typefaces Erika typefaces
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  20. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Clinical and molecular characteristics of childhood-onset Stargardt disease
    1
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    pubmed.ncbi.nlm.nih.gov/25312043/
  21. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    A Comprehensive Survey of Sequence Variation in the ABCA4 (ABCR) Gene in Stargardt Disease and Age-Related Macular Degeneration
    1
    1. Vibhor 09 Aug 2026
      STGD87 2588G→C Q1750X Yes

      Case#: STGD87, 10-14yo at onset, German

      DiseaseAssertion: STGD

      FamilyInfo: segregation in family

      CasePresentingHPOs:

      CaseHPOFreeText: "The diagnosis of STGD was based on the demonstration of bilateral impairment of central vision and the appearance of perimacular and/or peripheral yellow-white flecks, with or without atrophy of the central retinal-pigment epithelium and a normal or only mildly abnormal flash electroretinogram when recorded in early stages of the disease."

      CaseNotHPOs:

      CaseNotHPOFreeText:

      GenotypingMethod: denaturing gradient gel electrophoresis, dHPLC, and SSCP analysis, PCR amplification of individual coding exons and flanking intron sequences, direct DNA sequencing

      PreviouslyPublished: n/a

      Variant: Q1750X; 2588G→C in trans "Correct segregation of disease alleles was demonstrated in all 39 cases in which family samples were available for study"

      ClinVar: 7879

      CAID: CA119128

      SupplementalData: n/a

      CaseInfo Individual ClinVarID:7879 CAID:CA119128 automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
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    pmc.ncbi.nlm.nih.gov/articles/PMC1287885/
  22. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Bilateral visual loss, behavioral changes, and overlooking in a young child with stargardt disease: Neurodiagnostic considerations
    1
    1. Vibhor 09 Aug 2026

      Case#: Female, 6 years old, presenting with vision loss and behavioral changes.

      Disease Assertion: After testing she was diagnosed with Stargardt disease

      FamilyInfo: No family history of vision loss in childhood

      CasePresentingHPOs: HP:0000572, HP:0000708, HP:0007988, HP:0008001, HP:0030609

      CaseHPOFreeText: Showed changes in behavior through increased reliance on parents, and "Over the past six months, she had become increasingly emotional, anxious, frustrated, with difficulty concentrating on simple tasks". Additionally, beyond just the visual loss, she presented with 20/200 OU on her visual acuity test, as well as 1/14 Ishihara color plates with either eye. She also would overlook the top of objects, showed retinal arteriolar narrowing, had degeneration in the ellipsoid zone, and multiple hyperreflective granular deposits.

      CaseNotHPOs: HP:0000648, HP:0000486, HP:0000639, HP:0000613, HP:0001336, HP:0011145 (just seizures in general, this was the closest I could find)

      CaseNotHPOFreeText: Beyond the HPOs above, she also demonstrated a lack of seizures and had no other neurologic dysfunction. Additionally, she demonstrated brisk pupillary responses without paradoxical pupillary constriction to darkness. She also had normal results for the slip lamp biomicroscopy and tonometry.

      CasePreviousTesting: Previously tested for myoclonus, seizures, and neurologic dysfunction with no history of any (did not describe the testing methods for such).

      Genotyping Method: Although the genetic testing came up negative in relation to neuronal ceroid lipofuscinosis and the mutations associated, Stargardt disease was confirmed through whole genome sequencing. This revealed "compound heterozygosity for 2 pathogenic variants in the ABCA4 gene (c.3007 C > T p.Q1003X and c768 G > T PV256 = )".

      Previously Published: n/a

      Variant: NM_000350.3(ABCA4):c.3007C>T (p.Gln1003Ter) & NM_000350.3(ABCA4):c.768G>T (p.Val256=)

      ClinVarID: 4538557 & 99505

      CAID: n/a

      gnomAD: For the first ID the data for this one was absent from gnomAD (https://www.ncbi.nlm.nih.gov/clinvar/variation/4538557/?term=%22NM_000350.3(ABCA4)%3Ac.3007C%3ET+(p.Gln1003Ter)%22%5BVARNAME%5D). While the other ID had the minor allele frequency of 0.00009 (highest compared to others available) (https://www.ncbi.nlm.nih.gov/clinvar/variation/99505/?term=%22NM_000350.3(ABCA4)%3Ac.768G%3ET%22%5BVARNAME%5D+AND+%22(p.Val256%3D)%22%5BVARNAME%5D)

      Supplemental Data: Introduction was section in this article that discusses symptoms present as well as the re-diagnosis of Stargardt after the initial incorrect diagnosis of Batten disease. Additionally, Fig.1, Fig.2, and Fig.3 showed some of the phenotypes that appeared with this patient's condition.

      Gene:ABCA4 HGNC:34 InheritancePattern: NoInheritanceAssertion DiseaseAssertion:Stargardt Zygosity: NoZygosityAssertion 4) PreviousTesting 7) Bull'sEyeMaculopathy PreviousTesting automated_hgnc:34 automated_hgnc_source:hgnc_tag ClinGen ABCA4 Annotations
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    pmc.ncbi.nlm.nih.gov/articles/PMC8790276/
  23. onlinelibrary.wiley.com onlinelibrary.wiley.com
    Clinical and genetic characteristics of Stargardt disease in a large Western China cohort: Report 1
    1
    1. Vibhor 09 Aug 2026
      A total of 42 unrelated patients (28 men and 14 women) were included in this study. Two patients (A002 and A035) were from consanguineous families (Figure 1). The detailed clinical findings are presented in Data S1.

      Case#: Liu Proband A034, Chinese, female

      DiseaseAssertion: Stargardt

      FamilyInfo: Mother has the Pro68Leu variant, but the father was not genotyped to know the phase of the second variant. Proband's daughter also has the Pro68Leu variant, but is unaffected.

      CasePresentingHPOs:

      CaseHPOFreeText: no individual details provided

      CaseNotHPOs:

      CaseNotHPOFreeText: patients with other ocular diseases, such as choroidal neovascularization, glaucoma, and diabetic retinopathy, or were undergoing treatments/therapeutic trials were excluded.

      GenotypingMethod: Either eye gene-enriched (from 36 to 450 target genes) panel-based next-generation sequencing (NGS). Sanger bi-directional sequencing was conducted to confirm the rare candidate variants (allele frequency: less than 1.0% of the general population) and to perform the co-segregation analysis

      PreviouslyPublished: n/a

      Variant: c.203C>T p.(Pro68Leu); c.3883_3884del p.(Glu1295Lysfs*126)

      ClinVar: 99113

      CAID: CA226972

      SupplementalData: S1 only provides group demographics for the different clinical classifications (fundus grade, FAF type, etc)

      CaseInfo Individual SupplementalTable ClinVarID: 99113 CA226972 automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
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    onlinelibrary.wiley.com/doi/10.1002/ajmg.c.31838
  24. onlinelibrary.wiley.com onlinelibrary.wiley.com
    Inherited retinal disease in Norway – a characterization of current clinical and genetic knowledge
    1
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    onlinelibrary.wiley.com/doi/10.1111/aos.14218
  25. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Correlation of Outer Retinal Degeneration and Choriocapillaris Loss in Stargardt disease using en face OCT and OCT Angiography
    2
    1. Vibhor 09 Aug 2026
      11 M 53 c.5461–10T>C ND

      Case#: Patient 11, male, age 53

      DiseaseAssertion: STGD

      FamilyInfo: diagnosis of autosomal recessive STGD based on the pedigree and clinical phenotype of fleck deposits with or without genetic testing

      CasePresentingHPOs: HP:0000608, HP:0000007, HP:0030610, HP:0030500

      CaseHPOFreeText: Macular degeneration. autosomal recessive, Photoreceptor outer segment loss on macular OCT, Yellow/white lesions of the macula

      CaseNotHPOs: n/a

      CaseNotHPOFreeText: n/a

      Genotyping Method: n/a

      PreviouslyPublished: n/a

      Variant: NM_000350.3:c.5461-10T>C

      ClinVar: NM_000350.3(ABCA4):c.5461-10T>C

      CAID: CA220687

      SupplementalData: composite mask analysis shown in figure 3 for patient 11, show large areas of matched degeneration and isolated IS/OS loss

      CAID:CA220687 (6) DiseaseEntity:STGD1 (1) MacularFlecks InheritancePattern:AutosomalRecessive Gene:ABCA4 automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
    2. Vibhor 09 Aug 2026
      14 F 42 c.4222T >C c.4918C>T

      Case#: Patient 14, female, age 42

      DiseaseAssertion: STGD

      FamilyInfo: diagnosis of autosomal recessive STGD based on the pedigree and clinical phenotype of fleck deposits with or without genetic testing

      CasePresentingHPOs: HP:0000608, HP:0000007, HP:0030610, HP:0030500

      CaseHPOFreeText: Macular degeneration. autosomal recessive, Photoreceptor outer segment loss on macular OCT, Yellow/white lesions of the macula

      CaseNotHPOs: n/a

      CaseNotHPOFreeText: n/a

      Genotyping Method: n/a

      PreviouslyPublished: n/a

      Variant: Allele 1: NM_000350.3:c.4222T>C Allele 2: NM_000350.3:c.4918C>T

      ClinVar:Allele 1: NM_000350.3(ABCA4):c.4222T>C (p.Trp1408Arg) Allele 2: NM_000350.3(ABCA4):c.4918C>T (p.Arg1640Trp)

      CAID:Allele 1: CA227166 Allele 2: CA227253

      SupplementalData: composite mask analysis shown in figure 3 for patient 14, show diffusely intact IS/OS and RPE with central area of mixed types of degeneration. Both patient 2 and 14 show foveal preservation of IS/OS and RPE

      CAID:CA227166 CAID:CA227253 InheritancePattern:AutosomalRecessive (1) MacularFlecks (6) DiseaseEntity:STGD1 Gene:ABCA4 automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
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    pmc.ncbi.nlm.nih.gov/articles/PMC6548611/
  26. academic-oup-com.libproxy.lib.unc.edu academic-oup-com.libproxy.lib.unc.edu
    Mutations in ABCA4 result in accumulation of lipofuscin before slowing of the retinoid cycle: a reappraisal of the human disease sequence
    1
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    academic-oup-com.libproxy.lib.unc.edu/hmg/article-abstract/13/5/525/575460
  27. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Comprehensive analysis of Stargardt macular dystrophy patients reveals new genotype-phenotype correlations and unexpected diagnostic revisions
    1
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    ncbi.nlm.nih.gov/pmc/articles/PMC4385427/
  28. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Targeted sequencing and in vitro splice assays shed light on ABCA4-associated retinopathies missing heritability
    1
    1. Vibhor 09 Aug 2026
      Table S9. List of unique causative variants detected in 858 STGD probands mmc8.xlsx (19.3KB, xlsx) Table S11. STGD1 cases with at least two (likely) causal ABCA4 variants mmc9.xlsx (39.6KB, xlsx)

      Case#: DNAID 072888/Pat258, female

      DiseaseAssertion: STGD1

      FamilyInfo: n/a

      CasePresentingHPOs:

      CaseHPOFreeText: "In classic STGD1, loss of central vision starts around the second decade of life, but both early- and late-onset subtypes have been extensively described." No patient-specific details provided

      CaseNotHPOs:

      CaseNotHPOFreeText:

      GenotypingMethod: smMIPs sequencing of the complete ABCA4 locus

      PreviouslyPublished: n/a

      Variant: c.6416G>C (p.Arg2139Pro); c.3323G>A (p.Arg1108His)

      CAID: CA10611614

      SupplementalData: tables s9 and s11

      CAID:CA10611614 CaseInfo Individual SupplementalTable automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
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    pmc.ncbi.nlm.nih.gov/articles/PMC10534262/
  29. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Functional Analysis and Classification of Homozygous and Hypomorphic ABCA4 Variants Associated with Stargardt Macular Degeneration
    1
    1. Vibhor 09 Aug 2026
      The locations of ABCA4 homozygous and hypomorphic missense mutations characterized in the present study are shown in Fig 1. These mutations are distributed throughout ABCA4 with 4 in ECD1 (p.Asn96Asp, p.Asn96His, p.Arg212Cys, p.Arg602Trp), 4 in ECD2 (p.Leu1430Pro, p.Gly1439Asp, p.Pro1486Leu, p.Ala1598Asp), 6 within or close to NBD1 (p.Gly863Ala, p.Asn965Ser, p.Thr1019Met, p.Glu1087Lys, p.Arg1108Cys, p.Arg1129Leu), and 6 within NBD2 (p.Leu1940Pro, p.Gly1977Ser, p.Leu2027Phe, p.Arg2030Gln, p.Arg2107His, p.Cys2137Tyr). The p.Asn1868Ile mutation is present in a loop connecting the V-shaped α-helical hairpin with membrane spanning segment 12 (TM12). Several mutations occur in well-defined motifs crucial for the binding and hydrolysis of ATP. The p.Asn965Ser and p.Glu1087Lys mutations occur in the Walker A (Gly-His-Asn-Gly-Ala-Gly-Lys-Thr) and Walker B (Val-Ile-Leu-Asp-Glu) motifs of NBD1, respectively, and the p.Gly1977Ser mutation is present in the Walker A (Gly-Val-Asn-Gly-Ala-Gly-Lys-Thr) motif of NBD2. The p.Arg2030Gln variant reported to display a mild disease phenotype in compound heterozygous STGD1 patients has been included in our analysis although this variant has yet to be found in a homozygous state.

      A ClinVar entry claimed this variant showed "impaired substrate binding capacity and limited substrate release after ATP binding," but it is not found in the text or figures and there is no supplementary data.

      ClinVarID: 99135 NoEvidence CA227000 automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
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    ncbi.nlm.nih.gov/pmc/articles/PMC7755071/
  30. oce-ovid-com.libproxy.lib.unc.edu oce-ovid-com.libproxy.lib.unc.edu
    STARGARDT DISEASE: Beyond Flecks and Atrophy
    1
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    oce-ovid-com.libproxy.lib.unc.edu/article/00006982-201712000-00019/HTML
  31. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Phenotype–genotype correlations in a pseudodominant Stargardt disease pedigree due to a novel ABCA4 deletion–insertion variant causing a splicing defect
    1
    1. Vibhor 09 Aug 2026
      The proband

      Case#:case 1 II:4

      DiseaseAssertion: Stargardt disease (STGD1)

      FamilyInfo: mother has identical phenotype as proband, dad and sister asymptomatic, brother was symptomatic at 8 years old, other brother symptomatic at 15 years old.

      CasePresentingHPOs: HP:0000007

      CaseHPOFreeText: at age 50, with central visual imparement in right eye, 20/40 right, 20/20 left, linear and branching hyperautofluorescent subretinal deposits and extrafoveal RPE atrophy in both eyes,

      CaseNotHPOs: n/a

      CaseNotHPOFreeText: n/a

      Genotyping Method:

      PreviouslyPublished: n/a

      Variant: c.6031_6044delins18M/p.(Ile2003LeufsTer41)

      ClinVar: not found

      CAID: not found

      SupplementalData:

      PMID:32627976 HGNC:34 Gene:ABCA4 General Deletion automated_hgnc:34 automated_hgnc_source:hgnc_tag ClinGen ABCA4 Annotations
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    pmc.ncbi.nlm.nih.gov/articles/PMC7336727/
  32. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Correlating the Expression and Functional Activity of ABCA4 Disease Variants With the Phenotype of Patients With Stargardt Disease
    1
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    ncbi.nlm.nih.gov/pmc/articles/PMC5937799/
  33. www-sciencedirect-com.libproxy.lib.unc.edu www-sciencedirect-com.libproxy.lib.unc.edu
    ABCA4 mutational spectrum in Mexican patients with Stargardt disease: Identification of 12 novel mutations and evidence of a founder effect for the common p.A1773V mutation
    1
    1. Vibhor 09 Aug 2026
      616; 41c.2453G>A; c.5824G>Cp. G818E (D); p. E1942Q (B;N)46c.6384A>Gp.H2128R (D)Compound heterozygous

      Case#: Sporadic Case #16, Mexican

      DiseaseAssertion: Stargardt

      FamilyInfo: n/a

      CasePresentingHPOs:

      CaseHPOFreeText: STGD diagnosis based on: "onset of symptoms in childhood or early adulthood (before 20 years of age), bilateral central vision loss (central and peripheral visual field computerized testing), a retinal “beaten-bronze” foveal appearance and/or yellow-whitish flecks from the posterior pole to the mid periphery, normal caliber of the retinal vessels, no pigmented bone spicules in the retinal periphery, a normal to subnormal electroretinogram, and a typical dark choroid in fluorescein angiography."

      CaseNotHPOs:

      CaseNotHPOFreeText:

      PreviouslyPublished: n/a

      Variant: allele 1: c.2453G>A (p. G818E); c.5824G>C (p. E1942Q) allele 2: c.6384A>G (p.H2128R) direct sequencing of exons of ABCA4

      ClinVar: 867010

      CAID: CA957117

      SupplementalData: n/a

      CA957117 ClinVarID: 867010 CaseInfo Individual automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
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    www-sciencedirect-com.libproxy.lib.unc.edu/science/article/pii/S0014483513000420
  34. www.ajo.com www.ajo.com
    mmc1.pdf
    1
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    ajo.com/cms/10.1016/j.ajo.2020.06.027/attachment/2c3c8baa-ae3a-4cb6-a3ad-ae429569a986/mmc1.pdf
  35. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Intersection of Stargardt Dystrophy and AIDS: A Case Report
    1
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    pmc.ncbi.nlm.nih.gov/articles/PMC11844323/
  36. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Detailed genetic characteristics of an international large cohort of patients with Stargardt disease: ProgStar study report 8
    1
    1. Vibhor 09 Aug 2026
      Supplementary data. bjophthalmol-2018-312064supp004.pdf

      This variant is found on pg 16 in proband 14075. Compound heterozygous for c.6817-2A>C. MEH institute (UK). Said to have Stargardt based on the following criteria: "(1) patients (at least 6 years old) with at least two ABCA4 variants or one ABCA4 variant associated with a typical STGD1 phenotype and (2) presence of a well-defined atrophic lesion with/without flecks at the most recent visit of at least 300 µm in diameter (the total area of all lesions <12 mm2)." No additional details provided

      CA227000 ClinVarID: 99135 CaseInfo Individual SupplementalTable automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
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    ncbi.nlm.nih.gov/pmc/articles/PMC6579578/
  37. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Detailed analysis of an enriched deep intronic ABCA4 variant in Irish Stargardt disease patients
    1
    1. Vibhor 09 Aug 2026
      Pt-75Mc.4539 + 2028C > Tp.[= ,Arg1514Leufs*36]c.2453G > Ap.(Gly818Glu)

      Case#: Pt 7, male, 60yo at report, onset between 6-49yo, Irish

      DiseaseAssertion: Stargardt

      FamilyInfo: family 5

      CasePresentingHPOs:

      CaseHPOFreeText: VA: OD=6/36 OS=6/120, FAF and OCT in figure 2, FAF WRT vascular arcades=beyond, beaten bronze appearance, yellow flecks centrally, peripapillary sparing, central retinal thickness: OD=100 microns OS=117 microns, optical coherence tomography (OCT) atrophy horizontal width: OD=6000 microns OS=5446 microns

      CaseNotHPOs:

      CaseNotHPOFreeText: bulls eye pattern, flecks peripherally

      GenotypingMethod: Target capture NGS of the exons and known pathogenic intronic regions of ABCA4, whole-gene single molecule molecular inversion probe (smMIP) based sequencing of ABCA4 as well as 40 kb of flanking sequence, direct Sanger sequencing, or WGS

      PreviouslyPublished: n/a

      Variant: c.4539 + 2028C > T p.[= ,Arg1514Leufs*36]; c.2453G> A p.(Gly818Glu)

      ClinVar: 99135; 236116

      CAID: CA227000; CA10576057

      SupplementalData: n/a

      CA227000 ClinVarID: 99135 ClinVarID: 236116 CA10576057 CaseInfo Individual automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
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    ncbi.nlm.nih.gov/pmc/articles/PMC10256698/
  38. iovs.arvojournals.org iovs.arvojournals.org
    Phenotypic Spectrum of Autosomal Recessive Cone–Rod Dystrophies Caused by Mutations in the ABCA4 (ABCR) Gene
    1
    1. Vibhor 09 Aug 2026
      Patients and Methods The protocol of the study adhered to the provisions of the Declaration of Helsinki. After informed consent was obtained, blood samples were taken and molecular analysis on the ABCA4 gene was performed as described by Maugeri et al. 14 The charts of patients with ABCA4 mutations who originally had received diagnoses of isolated or autosomal recessive CRD were reviewed. All patients originated from the University Medical Centre Nijmegen (Nijmegen, The Netherlands) and the University of Heidelberg (Heidelberg, Germany). In this study the diagnosis of CRD was based on the following criteria: initial symptoms of blurred central vision without a history of night blindness, impairment of color vision, and fundoscopic evidence of maculopathy without or with mild peripheral retinopathy. 3 4 5 7 8 In patients with recordable ERGs a cone–rod pattern of degeneration had to be present (i.e., the photopic b-wave impairment had to be greater than or equal to the scotopic b-wave amplitude impairment). Patients 9250 and 13163, who had nonrecordable ERGs, were included because their histories and clinical features were similar to those of other patients with cone–rod degeneration and they were believed to represent advanced cases of CRD. In addition to an ophthalmic examination, Goldmann kinetic perimetry routinely was performed using III-4-e and I-4-e isopters. Color vision was tested with the Ishihara and Panel D15 tests, except in patients 9369, 9378, and 10125, who were tested under conditions described earlier. 18 Because these patients were examined in two different clinics and ERGs were recorded over a long period, the methods, instrumentation, and analysis techniques of the electroretinography varied. The ERGs in patients 9369, 9378, 10125, and 11872 were performed as described by Thijssen et al. 19 The ERG method used in patients 9370, 9553, 9633, and 13163 was described by Alexandridis and Krastel. 20 The ERGs of the remaining patients (9250, 9371, and 9650) are of a more recent date and were performed according to International Society for Clinical Electrophysiology of Vision (ISCEV) standards. 21 Fundus photographs were taken in most patients and some of the patients (9650, 9369, 9378, and 10125) also underwent fluorescein angiography.  Results The characteristics of 12 patients with ABCA4-associated retinal dystrophy resembling CRD are summarized in Table 1 . Most did not have affected family members, and therefore their retinal dystrophies could not be classified as autosomal dominant, autosomal recessive or X-linked. Four patients reported a brother or sister with subnormal vision. In view of the reputedly normal visual acuity of the parents and the molecular defects, the inheritance pattern of the gene defects in these patients (individuals 9303, 9369, 9553, and 13163) was classified as autosomal recessive.  The visual acuity of the patients did not exceed 20/200 and, on average, was much lower. With the exception of patient 9553, the age of onset was at or before the age of 12, and in each of the patients, blurred vision was the initial symptom. Night blindness did not occur except in patients 9378 and 10125, in the final stages of retinal degeneration. Evidence of maculopathy in the form of bull’s eye maculopathy or pigmentary changes was present in all the patients reported in this study (Fig. 1A) . The functional equivalent of the mainly centrally located retinal disease was a central scotoma, varying from 8° to more than 40°. In all but one patient, the scotoma was absolute. Only in patient 9378 was the central scotoma relative and surrounded by absolute scotomas. Fundoscopic evidence of early peripheral involvement of the retina was mild, and only in the later stages of the disease did peripheral changes characteristic of RP, such as narrowing of retinal vessels and bone spicula, occur in patients 9369 (Fig. 1B) and 10125. Similarly, mild constriction of the visual fields occurred only in two patients (9650 and 10125) and only in the advanced state. Color vision was tested in 10 patients. Six demonstrated a red–green defect, and in two of these (patients 11872 and 10125), it was accompanied by a blue-yellow defect. In the remaining four patients, color vision was so severely disturbed that the exact type of impairment could not be assessed.  The ERG recordings demonstrated degeneration of both rods and cones. When ERG responses could be elicited, the cones appeared to be affected as much as the rod photoreceptors and, in most of the patients, even more severely. The ERG responses in five patients progressively deteriorated until no photopic and scotopic responses could be recorded. In these patients, with exception of patients 9250 and 13163, ERG recordings of an earlier date were used in Table 1 . This applies to patient 9369, in whom an ERG was recorded at age 12 (all ERG responses had been nondetectable since the age of 21), patient 9378 at age 33 (all ERG responses at age 46 were nondetectable), and patient 10125 at age 8 (in 1998, at age 28, the ERG responses were no longer detectable). Recent ERG findings were not available for patients 9650 and 9371. Their ERGs were recorded in 1989 and 1985, respectively. The remaining ERG data were derived from ERG recordings performed in the past 4 years. Of patient 9371 only the ERG data in the left eye were available.  Two patients warrant a more detailed description, due to the unusual course of their retinal dystrophies. Patient 9378, at the age of 12, had blurred vision with fundoscopic evidence of irregular chorioretinal atrophy in the posterior pole. At that time, there were no peripheral abnormalities on ophthalmoscopy, and there was no history of night blindness. The ERG demonstrated an equal reduction of both cone- and rod-mediated responses. Later in life, however, fundoscopic changes developed that were characteristic of RP, and the patient reported a decrease in night vision. With fluorescein angiography partly confluent patches of chorioretinal atrophy were visible (Fig. 1C) .  The clinical picture of patient 10125 differed from that of the other patients, despite the mutation in the ABCA4 gene. Initially, disease in this patient was diagnosed as STGD because of the bull’s eye maculopathy, the granular pigment alterations in the macular area, and the pisciform flecks surrounding the posterior pole. At age 8 his visual acuity had decreased to 20/200 in both eyes. When he was referred to our clinic in 1998 at the age of 28, peripheral degeneration in the form of narrow retinal vessels and deposition of peripheral bone spicula had developed, in addition to the earlier described disease of the central retina. A fluorescein angiogram showed typical findings: a central small hypofluorescent spot enclosed by an ellipsoid—a markedly hyperfluorescent area that in turn was surrounded by hyperfluorescent dots against a dark background, most likely caused by obscuration of choroidal background fluorescence (Fig. 1D) . Early ERG recordings were not available, and the ERG tracings recorded at age 28 represent the final stage of the degenerative process, with absence of both cone and rod responses. This retinal dystrophy seemed to have evolved from STGD into more widespread retinal degeneration, resulting in loss of function of both rods and cones.  Discussion Progressive CRD is a clinically heterogeneous retinal disorder, but typical findings include reduced visual acuity, impairment of the central visual field, color vision deficits, and fundoscopic evidence of maculopathy, with no or few midperipheral retinal pigment deposits. 3 4 7 8 There is some dispute about typical ERG findings in CRD. Some state that the diagnosis of CRD must be based on the reduction or absence of cone responses in the presence of quantitatively less reduction in rod responses, whereas others state that an equal impairment of both photoreceptor systems, if accompanied by the characteristic features, suffices to justify the diagnosis of CRD. 3 7 8 22 Several propositions have been made in the past to classify cone–rod disorders. Some classification systems have focused on individual case reports and were based on nosologic aspects; others have made a distinction according to the various patterns of inheritance. 3 6 23 24 In recent studies, Szlyk et al. 7 and Yagasaki et al. 8 made use of full-field ERGs, dark adaptometry, and modified perimetric techniques to identify functionally distinct subtypes of CRD. Finally, over the past few years, a molecular genetic classification of CRD has emerged.  At the moment, four genes and three loci have been implicated in autosomal dominant CRD, whereas one X-linked locus has been described. 25 26 27 28 29 30 31 32 Thus far, two loci and one gene (ABCA4) have been associated with autosomal recessive CRD. 12 33 34 The genetic heterogeneity seen in CRD is matched by the range of the clinical findings attributed by various investigators to this type of retinal dystrophy.  Whatever the classification system used, some patients display retinal disorders that cannot be classified satisfactorily. Often, these retinal degenerations involve overlapping features. Krill et al. 5 reported that 9 of 45 patients with cone degenerations showed typical features associated with fundus flavimaculatus. Heckenlively 2 described 76 patients with cone–rod patterns on the ERG in whom retinal disease otherwise met the standard definition of RP (progressive peripheral visual field loss with ring scotoma). Alternatively, as seen in patient 10125 in this study, patients with STGD have been described who had progressive peripheral retinal degeneration with severe abnormalities in the ERG and electro-oculogram (EOG) later in life—a condition that has been described by Fishman 4 as secondary progressive cone–rod dysfunction.  The association of CRD and a dark choroid has also been described previously. 35 36 The atypical pattern of retinal degeneration with confluent patches of chorioretinal atrophy in patient 9378 resembles that in another previously described unrelated patient with CRD-like disease caused by mutations in ABCA4. 37 In the molecular genetic study by Maugeri et al., 14 in which 11 of the 12 patients with autosomal recessive CRD described in this study were analyzed, ABCA4 mutations were found in 13 of 20 unrelated patients, strongly suggesting that ABCA4 mutations are the major cause of this disorder. If this is true, the genetic heterogeneity in autosomal recessive CRD, compared with, for example, classic RP, is surprisingly low. Because autosomal recessive inheritance is believed to be the most frequent mode of inheritance of monogenic chorioretinal disorders, it is very possible that a large fraction of the patients with CRD who have been clinically studied previously carry ABCA4 mutations. In that case, the explanation for the high variability of the clinical findings in autosomal recessive CRD would not be genetic heterogeneity but rather the genotype–phenotype model for ABCA4. According to this model, there is an inverse relationship between the presumed residual ABCA4 function as an N-retinylidene-PE flippase and the severity of the disorder. 12 37 38 As a consequence, a continuum of phenotypes is to be expected, ranging from STGD to CRD to RP. Although this is probably a simplified representation of reality and needs corroboration by detailed biochemical studies of individual mutations, as described previously, this model explains why mutations in the ABCA4 gene could give rise to phenotypes that do not satisfy the standard classification of retinal dystrophies. 39   Two patients in this study may reflect borderline CRD phenotypes. Patient 9553 carries a combination of a mild (2588G>C) and severe ABCA4 mutation, which, according to the genotype–phenotype model described earlier, should be associated with STGD. We have previously discussed that most likely, one of the pathologic mutations has not yet been identified in this patient. 14 However, the age of onset in this patient (25 years) is relatively high, and although other features such as visual acuity, perimetry, and ERG findings are typical of CRD, this may indicate a relatively mild subtype. Another more convincing example of blending of ABCA4-associated phenotypes is patient 10125. The molecular findings in this patient have not yet been described elsewhere. He carries a severe splice site mutation (IVS30+1G→T) in combination with a nucleotide change leading to a stop codon at Gln1029. A patient with RP who was homozygous for the IVS30+1G→T mutation has been described, 12 whereas the Q1029X mutation has not been described. Both mutations can be considered to be null alleles. According to the proposed ABCA4 model, the clinical phenotype in patient 10125 should be RP. Instead, this patient exhibits a typical retinal dystrophy, which gradually progresses from STGD to a more widespread degeneration of photoreceptors in a cone–rod pattern later in life. At present, both rod and cone ERG responses are not detectable, indicative of a final stage similar to that in many patients with RP. Functional studies are necessary to clarify whether these specific ABCA4 mutations are responsible for the particular progression of the retinal degeneration in this patient, or whether other as yet unknown modifying factors play a role.  In this study we have described 12 unrelated patients with retinal dystrophy resembling CRD caused by mutations in the ABCA4 gene. In a previous study we described the ophthalmic features in five siblings with CRD-like retinal dystrophy who were carrying ABCA4 mutations. 37 From the clinical data of these patients and previous molecular studies in patients with autosomal recessive CRD, two important conclusions can be drawn. 12 14 First, the genetic basis of autosomal recessive CRD is less heterogeneous than was thought, based on the variability in clinical features, because mutations in the ABCA4 gene seems to be the major pathologic cause. Second, given the wide clinical spectrum of CRD-like phenotypes associated with ABCA4 mutations, detailed clinical subclassifications are difficult and may not be very useful.   Supported by the British Retinitis Pigmentosa Society, the Rotterdamse Vereniging Blindenbelangen, the Algemene Nederlandse Vereniging ter Voorkoming van Blindheid, the Stichting Blindenhulp, the Stichting de Drie Lichten, the Gelderse Blindenvereniging and the Landelijke Stichting voor Blinden en Slechtzienden and the Stichting voor Ooglijders.  Submitted for publication June 15, 2001; revised December 21, 2001; accepted January 2, 2002.  Commercial relationships policy: N.  The publication costs of this article were defrayed in part by page charge payment. This article must therefore be marked “advertisement” in accordance with 18 U.S.C. §1734 solely to indicate this fact.  Corresponding author: B. Jeroen Klevering, Department of Ophthalmology, University Medical Centre Nijmegen, PO Box 9101, 6500 HB, Nijmegen, The Netherlands; b.klevering@ohk.azn.nl. Table 1. View Table Patients with Cone–Rod Degeneration and ABCA4 MutationsTable 1. Patients with Cone–Rod Degeneration and ABCA4 Mutations Patient Sex Current Age (ys) ABCA4 Mutations* Visual Acuity Age of Onset (ys) Fundoscopy Color Vision Perimetry ERG Cone (μV), † ERG Rod (μV), † OD OS OD OS OD OS 9250 M 30 1622T→C; 3113C→T 194G→A CF CF 6 Pigment clumping in the macula NP Large central scotoma over 40° ND, ‡ ND, ‡ 9303 M 21 1622T→C; 3113C→T 20/400 20/400 7 Granular pigmentary changes in the macula Diffusely disturbed Central scotoma of 20° Severely decreased, § Severely decreased, § 9369 F 40 6601-6602deIAG LP LP 8 Irregular hypopigmentation, mainly in the posterior pole. In later stages: attenuated vessels and bone spicula temporal to the macula Red-green defect Central scotoma varying from 10–30° 65 (65%) 80 (80%), ∥ 140 (90%) 160 (nl), ∥ 9370 M 15 1622T→C; 3113C→T 20/200 20/200 7 Granular aspect of the macula NP Concentric central scotoma of 8° 10 (13%) 9 (13%), ¶ 29 (29%) 29 (23%), ¶ 9371 M 38 1622T→C; 3113C→T 1622T→C;3113C→T 20/400 20/400 10 Bull’s eye maculopathy Red-green defect Concentric central scotoma of 20° NP 29 (16%), ‡ NP 54 (30%), ‡ 9378 F 50 768G→T CF CF 12 Bull’s eye maculopathy, narrow vessels in periphery with mild granular changes of the pigment epithelium and confluent patches of chorioretinal atrophy Severely disturbed Large, absolute, paracentral scotomas, relative scotoma centrally 20 (20%) 30 (30%), ∥ 70 (47%) 90 (60%), ∥ 9553 F 45 2588G→C IVS35del-2→+2del4 20/400 20/400 25 Bull’s eye maculopathy. Peripheral diffuse motting of RPE Severely disturbed Large central scotoma over 40° 14 (14%) 19 (19%), ¶ 41 (41%) 24 (24%), ¶ 9633 M 22 1622T→C; 3113C→T 4469G→A 20/400 20/200 12 Atrophy of retinal pigment epithelium in posterior pole. Early stages of bull’s eye maculopathy Red-green defect Central scotoma of 20° 12 (16%) 12 (16%), ¶ 61 (62%) 39 (39%), ¶ 9650 F 20 3364G→A 20/400 20/400 5 Central granular aspect Red-green defect Large central scotoma of 30° and relative constriction of III-4 70 (39%) 106 (59%), ‡ 272 (nl) 115 (76%), ‡ 10125 M 30 IVS30+1G→T 3085C→T 20/200 20/200 8 Central hypopigmentation with dark surrounding, resembling bull’s eye. Later in life: peripheral changes characteristic of RP Severe red-green defect; mild blue-yellow defect Central scotoma of 10–15° with mild peripheral restriction 75 (75%) 80 (80%), ∥ 130 (87%) 140 (93%), ∥ 11872 M 30 634C→T 20/200 20/200 10 Bull’s eye pattern Severely disturbed; blue-yellow more than red-green Central scotoma of 25° 23 (23%) 35 (35%), ∥ 110 (73%) 95 (63%), ∥ 13163 M 15 1622T→C;3113C→T IVS36+1G→A 20/400 20/200 6 Granular aspect of retinal pigment epithelium in macula. Slightly pale optic disc Severely disturbed Central scotoma of 10–15,° no peripheral involvement ND, ¶ ND, ¶  CF, count fingers; LP, light perception; ND, not detectable; NP, not performed. *  Allele 1, first line; allele 2, second line. †  Between parentheses: percentage of the ERG value compared to the lower limit of the normality; normal ERG values are indicated nl. ‡  Minimal values for ERG recordings: 150 μV for the photopic ERG, 180 μV for the scotopic ERG. §  ERG performed with skin electrodes. ∥  Minimal values for ERG recordings: 100 μV for the photopic ERG, 150 μV for the scotopic ERG. ¶  Minimal values for ERG recordings: 99 μV for the photopic ERG, 75 μV for the scotopic ERG. Figure 1. View OriginalDownload Slide (A–D) Fundus photographs and fluorescein angiograms in eyes of patients with (atypical) CRD. (A) Patient 11872 with bull’s eye maculopathy. (B) Patient 9369, demonstrating CRD in the later stages with attenuation of the retinal arterioles and irregular pigmentation temporal to the macula. (C) Fluorescein angiograms in patient 9378 showing confluent patches of chorioretinal atrophy. (D) Patient 10125 with central hypofluorescence enclosed by an ellipsoid hyperfluorescent area. In the surrounding area, hyperfluorescent flecks are visible, and the choroidal background fluorescence seems blocked, as seen in STGD.

      Case#: Klevering Patient 9369, female, Netherlands, 40yo at report, 8yo at onset

      DiseaseAssertion: cone-rod degenerations/ ABCA4-associated retinal dystrophy resembling CRD

      FamilyInfo: "In view of the reputedly normal visual acuity of the parents and the molecular defects, the inheritance pattern of the gene defects in these patients (individuals 9303, 9369, 9553, and 13163) was classified as autosomal recessive."

      CasePresentingHPOs:

      CaseHPOFreeText: Visual acuity: light perception OU. Fundoscopy: Irregular hypopigmentation, mainly in the posterior pole. In later stages: attenuated vessels and bone spicula temporal to the macula. Red-green defect of color vision. Perimetry: Central scotoma varying from 10–30°. ERG Cone (μV): OD-80 (80%), OS-140 (90%) from 12 yo (all ERG responses had been non-detectable since the age of 21). ERG Rod (μV): 160 (nl). Fundus photographs and fluorescein angiograms show CRD in the later stages with attenuation of the retinal arterioles and irregular pigmentation temporal to the macula. Narrowing of retinal vessels and bone spicula (Fig 1B). Fundus description (PMID: 10958761): atrophy of the RPE around the optic disk, bone spicules along arteries and venules in the mid-periphery, and attenuated arterioles (Fig 1D)

      CaseNotHPOs:

      CaseNotHPOFreeText:

      GenotypingMethod: single-strand conformation polymorphism (SSCP) and direct-sequencing techniques to look for mutations in the 50 exons and flanking intron sequences of the ABCA4 gene

      PreviouslyPublished: Maugeri et al (PMID: 10958761)

      Variant: c.6601_6602delAG

      CAID: CA227421

      SupplementalData: n/a

      CaseInfo Individual CAID:CA227421 PreviouslyPublished automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
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  39. www.biorxiv.org www.biorxiv.org
    Negligible participation in the scientific literature of AI unicorn startups
    1
    1. jodischneider 08 Aug 2026

      Wikipedia tells me that "In finance, a unicorn is a privately held startup company with a current valuation of US$1 billion or more." Consider glossing this someplace in the abstract - the meta-science community likely has to search for this kind of info.

      definitions
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    biorxiv.org/content/10.64898/2026.07.15.738744v1
  40. freakonometrics.github.io freakonometrics.github.io
    Chapitre 5 — Faire confiance à celui qui paiera – La société au prix du risque
    4
    1. Monsieur__R 08 Aug 2026
      Une procédure peut enfin réduire l’indemnisation sans produire de refus explicite.

      C'est aussi le cas pour la fausse déclaration non intentionnelle : le règlement du sinistre sera réduit au prorata du rapport entre la prime payée et celle qui aurait dû être payée si le risque avait été correctement déclaré

    2. Monsieur__R 08 Aug 2026
      Les avances et les paiements partiels ont pour fonction de limiter cette asymétrie.

      Une autre configuration, c'est quand tu dois subir l'assurance d'autrui Je ne sais pas si tu abordes ce point, mais en France il existe aussi l'assurance décennale, qui couvre pendant dix ans les travaux réalisés par un artisan ou un constructeur. Elle fonctionne en tandem avec un autre mécanisme, l'assurance dommages-ouvrage (obligatoire sous certains aspects), qui indemnise rapidement le maître d'ouvrage (sans attendre qu'une responsabilité soit établie), puis se retourne ensuite contre l'assureur décennal du professionnel responsable. Si tu n'as pas souscrit de DO, tu es tributaire de la bonne volonté de l'assureur d'un artisan qui a pu cessé d'exister depuis des années !

    3. Monsieur__R 08 Aug 2026
      Pour l’assuré, le même délai peut signifier un logement inhabitable, un véhicule nécessaire au travail, une activité interrompue ou des soins reportés.

      Ca peut être d'autant plus complexe que certaines garanties sont portés par plusieurs assureurs dans un même contrat. Quand ma voiture est accidentée, c'est l'assistance qui va organiser mon remorquage et mon rapatriement, mais c'est l'assureur principal qui va payer pour les travaux du véhicule. Si je suis blessé, la GPC peut être portée par un troisième assureur, et pourra éventuellement être complété par ma GAV et mon quatrième assureur.

    4. Monsieur__R 08 Aug 2026
      L’assuré verse une prime pendant des mois ou des années. Il devient créancier d’une indemnité seulement si un événement prévu par le contrat survient et si sa demande est reconnue.

      J'y pense maintenant, mais il y aussi l'aspect volet responsabilité civile qui est aussi intéressante à envisager dans la réflexion globale. Dans mon interaction avec la société, je profite aussi de cette confiance que, normalement, tout le monde est assuré contre les dommages qu'on pourrait m'occasionner.

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  41. www.biorxiv.org www.biorxiv.org
    Metabolic Rewiring by alpha-Synuclein Enables Mitohormetic Protection
    4
    1. EMBOpress 08 Aug 2026

      Note: This response was posted by the corresponding author to Review Commons. The content has not been altered except for formatting.

      Learn more at Review Commons

      Reply to the reviewers

      We thank you and the reviewers for the thoughtful and constructive evaluation of our manuscript, “Metabolic Rewiring by α-Synuclein Enables Mitohormetic Protection.” We appreciate the reviewers’ recognition that the study addresses an important and relatively underexplored aspect of αSyn biology, namely the physiological contribution of αSyn to cellular metabolism and adaptation to mitochondrial stress.

      In response to the reviewers’ comments, we have substantially revised the manuscript, added new experimental data, and clarified several points of interpretation. Importantly, we now include: (i) comparison of αSyn expression in the HEK293T αSyn-expressing clones with endogenous αSyn levels in mouse brain lysates; (ii) additional analysis of αSyn-immunoreactive high-molecular-weight species following chronic mild-dose rotenone treatment; (iii) a non-crosslinked co-immunoprecipitation control; (iv) PRX6-Flag as a negative control for the LDHA-Flag pull-down; (v) proximity ligation assay data in HEK293T cells; (vi) mitochondrial DNA and mitochondrial membrane potential measurements; (vii) Seahorse analysis of ECAR reserve capacity and OCR following acute and chronic mild-dose rotenone treatment.

      We also revised the wording throughout the manuscript to avoid overinterpretation. In particular, we now refer to LDHA as an αSyn-associated protein and to the PLA data as evidence for close proximity, rather than as definitive proof of direct binding. We also clarify that the growth advantage observed under chronic rotenone represents adaptation to chronic mild mitochondrial stress, not protection from acute severe toxicity.

      In addition, we made a substantial effort to address the relevance of our findings for PD and could successfully demonstrate, using proximity ligation assay, that endogenous αSyn associates with endogenous LDHA in cultured mouse primary hippocampal neurons. The fact that endogenous aSyn and LDHA associate with each other also in neurons argues that this association is likely to be relevant to PD. On the other hand, showing that overexpression of aSyn protects neurons from mitochondrial stress was more challenging, and so far, we could not find an experimental setting to demonstrate this. None-the-less, we laid the foundation for a longer-term approach, and we are in the process of expanding C57BL6 SNCA+/+ and SNCA−/− mouse colonies. These mice, and cultured primary neurons prepared from them, will be the ultimate approach to address the relevance of our findings to PD.

      We were also asked to contextualize our findings against contradictory literature, and thus added the following paragraph to the Discussion: “How do our findings contextualize against contradictory literature? For example, Lee et al reported that αSyn overexpression exacerbates rotenone-induced ATP loss, suggesting that αSyn indirectly sensitizes mitochondria to complex I inhibition by endogenous/exogenous stressors in cells [41]. Our findings challenge this view that αSyn is intrinsically toxic. We demonstrate that αSyn promotes mitohormesis: mild energetic stress induces adaptive bioenergetic remodeling. Based on our findings we propose that αSyn acts as a stress-response protein recruited during increased energetic demand to maintain bioenergetic homeostasis. This response preserves cellular function, whereas repeated demand may exhaust the program, leading to mitochondrial dysfunction, ATP loss, pathological αSyn conversion and cell death.”

      Point-by-point description of the revisions

      Reviewer 1

      Comment 1. Overexpression of α-synuclein does not seem to affect cell growth, but is its level in the range that might occur in living organisms?

      Response: We thank the reviewer for raising this important point. To address it, we added a new Western blot comparison between αSyn expression in HEK293T αSyn-expressing clones and endogenous αSyn levels in mouse brain lysates. This analysis is now shown in Supplementary Fig. 1B. As expected, αSyn expression in the HEK293T stable clones is higher than in the endogenous tissue reference. We now explicitly state this in the Results section and have adjusted the interpretation accordingly. Importantly, despite this elevated expression, αSyn stable overexpression did not affect basal cell growth or transgene stability under standard culture conditions. Thus, while this model is not intended to reproduce endogenous neuronal αSyn levels, it provides a controlled gain-of-function system to uncover αSyn-dependent metabolic effects.

      Changes made:

      We added Supplementary Fig. 1B and revised the Results section to state that αSyn expression in HEK293T clones is higher than in mouse brain lysates. We also added the corresponding Methods section describing preparation of whole-brain lysates.

      Comment 2. Protein-protein interactions of α-synuclein are shown under treatment with supramaximal complex I inhibition. To show relevance of the interaction in resistance to prolonged and mild complex I inhibition, it would be important to show the protein complexes under those conditions.

      Response: We agree with the reviewer that it is important to distinguish between the effects of acute high-dose rotenone and chronic mild-dose rotenone. We therefore analyzed αSyn-immunoreactive high-molecular-weight species after chronic mild-dose (40nM) rotenone treatment. These data are now included in Supplementary Fig. 4. Interestingly, chronic mild-dose rotenone did not increase the intensity of the αSyn-immunoreactive HMW species. This suggests that increased formation of these HMW species is not required for the adaptive growth resilience observed after chronic mild-dose rotenone treatment. We have revised the Results section to discuss this point more explicitly. We also note that chronic treatment may alter the composition, localization, or functional state of αSyn-associated complexes, even if the overall abundance of DSG-captured HMW species is not increased.

      Changes made:

      We added Supplementary Fig. 4 and revised the Results section to clarify that acute and chronic high-/low-dose rotenone has distinct effects on αSyn-immunoreactive HMW species.

      Comment 3. Would it be possible to test the physiological relevance of α-synuclein by silencing/knockout strategy?

      Response: We agree that loss-of-function or endogenous models are important to support physiological relevance. We made a large effort to identify a cell line in which we could detect endogenous aSyn, to knock it out, and were not successful. We could detect endogenous aSyn only in mouse brain lysates (shown in Supplementary Fig. 1B), and therefore we are in the process of expanding C57BL6 SNCA+/+ and SNCA−/− mouse colonies. These mice, and cultured primary neurons prepared from them, will be the ultimate approach to test the physiological relevance of αSyn.

      Comment 4. Table 1 is difficult to understand and is not explained well by the legend.

      Response: We thank the reviewer for pointing this out. We have rewritten the legend to Table 1 to explain the LC-MS/MS analysis, the meaning of the columns, and the interpretation of peptide-spectrum matches, unique peptides, and protein coverage.

      Changes made:

      We revised the Table 1 legend to improve clarity.

      Comment 5. Fig. 2A scale bar 20uM has to be changed to 20µm.

      Response: We thank the reviewer for noting this error. The scale bar label has been corrected to 20 µm.

      Changes made:

      We corrected the scale bar label in Fig. 2A and checked additional figure panels for similar unit-formatting issues.

      Reviewer 2

      Comment 1. For one, the proposed interaction of LDHA and αSyn was only studied by coimmunoprecipitation of tagged and crosslinked proteins after massive transient overexpression in HEK cells. As HEK cells only express very low and negligible amounts of endogenous αSyn this overexpression probably results in vast amounts of mislocalized αSyn. No attempts are described to verify this interaction in a more relevant cellular model with endogenous proteins. I would ask for native co-immunoprecipitation with and without crosslinking and proximity ligation assays from at least something like SH-SY5Y cells which express endogenous αSyn.

      Response: We agree with the reviewer, and below is a description of the new experiments we performed and data added to the revised manuscript:

      • We used PRX6-Flag as a FLAG-tagged negative control protein in the co-immunoprecipitation experiment, and showed that αSyn-HA was detected in the LDHA-Flag pull-down but not in the PRX6-Flag control pull-down, supporting specificity of the LDHA-associated αSyn signal (Fig 1C).
      • we performed co-immunoprecipitation without crosslinkers in HEK293T cells co-expressing LDHA-Flag and αSyn-HA. In the absence of DSG, αSyn was not detected in LDHA-Flag immunoprecipitates )supp Fig. 2B), suggesting that the LDHA-αSyn association is not efficiently preserved under conventional lysis and immunoprecipitation conditions. We envision that the αSyn-LDHA complex requires the intact cellular setting to remain a complex, and DSG preserves this setting.
      • We performed a proximity ligation assay (PLA; [31]) in intact HEK293T cells and in intact mouse primary hippocampal neurons.
      • HEK293T cells: Using antibodies against LDHA and aSyn, we detected a high PLA signal in aSyn-expressing cells, and a very low signal in vector control cells (Supp Fig. 2C).
      • Mouse primary hippocampal neurons: Using antibodies against LDHA and aSyn, we detected endogenous LDHA and endogenous αSyn, without tagged protein overexpression, in neurons prepared from ICR-SNCA+/+ and C57BL6JHUK-SNCA−/− mice. In this experiment we observed a robust PLA signal in ICR-SNCA+/+ neurons and a very low signal in C57BL6JHUK-SNCA−/− neurons (Supp Fig. 3B, C). These new results add important support that aSyn associates with LDHA, but additional data are needed to confirm direct binding, e.g., AlphaFold-based structural predictions to model potential binding interfaces. Therefore, we revised the wording throughout the manuscript, and we now use “associates with”, “αSyn-associated” and “close proximity” where appropriate, and we avoid using “direct interaction”.

      Changes made:

      We added PRX6-Flag control data in Fig. 1C, non-crosslinked co-IP in Supplementary Fig. 2B, PLA in Supplementary Fig. 2C and Supplementary Fig. 3, and revised the wording throughout the manuscript.

      Comment 2. αSyn was expressed with an IRES-GFP but the control contained only GFP which is not ideal. It is unclear why rotenone results in increased levels of αSyn. Less degradation, increased expression? At least a qPCR could help.

      Response: We agree that the vector design should be considered when interpreting the data. The αSyn construct expresses αSyn-IRES-GFP, whereas the control expresses GFP from the corresponding empty IRES-GFP vector. We emphasize that the major metabolic comparisons were performed across multiple independent αSyn-expressing and vector-control clones, reducing the likelihood that the observed effects reflect a single clonal artifact.

      Regarding the 2nd part: “It is unclear why rotenone results in increased…

      Response: We thank the reviewer for this important point. We have revised the text to clarify that we do not interpret the increased αSyn signal after chronic mild-dose rotenone as evidence for transcriptional induction or altered degradation. Because the αSyn construct is linked to IRES-GFP, the shift toward higher GFP intensity after chronic low-dose rotenone strongly suggests enrichment or selective expansion of cells with higher transgene expression, rather than necessarily increased expression within each individual cell. This interpretation is supported by both fluorescence microscopy and flow cytometry showing enrichment of high-GFP cells specifically in the αSyn-expressing population.

      We agree that qPCR could distinguish between transcriptional upregulation and selection of high-expressing cells. However, because the FACS data already show a population shift in GFP intensity, and because the main conclusion is selection or enrichment of high αSyn-expressing cells under chronic mild mitochondrial stress, we have revised the wording to avoid claiming a specific mechanism of increased αSyn expression.

      Changes made:

      We revised the Results and the Fig. 2 legend to describe enrichment of high-GFP and high-αSyn-expressing cells, rather than implying transcriptional induction.

      Comment 3. For the claim that αSyn overexpression shifts metabolism toward increased glycolysis and OXPHOS, important controls are missing. What about cell numbers, mitochondrial mass, mitochondrial membrane potential, etc. Were these experiments done with or without rotenone preconditioning?

      Response: We agree that these controls are essential. ECAR and OCR measurements were normalized to cell number per well, as described in the Methods. In addition, we added new analyses of mitochondrial DNA content and mitochondrial membrane potential. These data are presented in the Supplementary Fig. 5C and 5D and show no differences between vector and αSyn-expressing clones in mitochondrial DNA content or mitochondrial membrane potential, either under basal conditions or after chronic 40nM rotenone treatment. These data support the conclusion that the observed metabolic differences are not simply explained by increased mitochondrial number or altered mitochondrial membrane potential.

      In the revised manuscript, we show that αSyn-expressing clones exhibit higher LDHA activity and increased lactate secretion both under basal conditions and after chronic low/mild-dose (40nM) rotenone treatment. We also added Seahorse analysis under acute and chronic mild-dose rotenone conditions. These data show that chronic mild-dose rotenone treatment abolished mitochondrial respiration in both aSyn- and vector clones (Supp Fig 6). In glycolysis, aSyn clones showed a larger increase in glycolytic capacity as compared to vector clones following chronic mild-dose rotenone treatment (Fig 4A, B).

      Importantly, we also detected differences between the aSyn- and vector clones in glycolytic reserve, which is the value obtained by the subtraction of the glycolysis capacity (max glycolysis) from the basal rate of glycolysis [34]. aSyn–expressing clones preserve high glycolytic reserve following either acute or chronic mild-dose rotenone treatment, whereas similar treatments abolish the glycolytic reserve in vector clones (Fig 4C). These results are consistent with the idea that the presence of aSyn enables cells to continue to proliferate by maintaining the glycolytic energy reserve when mitochondria energy production is abolished.

      Changes made:

      We added Supplementary Fig. 5C, Supplementary Fig. 5D, Fig. 4A and Supplementary Fig. 6, and revised the Seahorse Methods section.

      Comment 4. MitoSOX measures mitochondrial hydrogen peroxide and not mitoROS.

      Response: We agree that the readout should be described with greater precision. According to Thermo Fisher/Invitrogen, MitoSOX-Red is a mitochondrial superoxide indicator. They describe it as a mitochondria-targeted dye whose oxidation is by mitochondrial superoxide, O₂•⁻. MitoSOX-Red fluorescence is commonly used as a mitochondrial superoxide-sensitive signal, but it should not be interpreted as a comprehensive measurement of all mitochondrial reactive oxygen species. To avoid overinterpretation, we revised the relevant text to describe the signal more cautiously as MitoSOX-Red fluorescence or mitochondrial superoxide-sensitive ROS signal, where appropriate, rather than as a broad measure of total mitoROS.

      Changes made:

      We revised the Results, Methods, and figure legend terminology to define the MitoSOX-Red assay more precisely and to avoid overgeneralization.

      Reviewer 3

      Major comment 1. Figure 1C: The co-IP lacks important controls, such as cells expressing an empty vector or a FLAG-tagged non-interacting control protein (e.g., cytosolic GFP-FLAG). Also, IP alone does not sufficiently support a direct interaction between αSyn and LDHA. While co-association in a complex is evident, additional data are needed to confirm direct binding, e.g., AlphaFold-based structural predictions to model potential binding interfaces.

      Response: We agree with the reviewer, and below is a description of the new experiments we performed and data added to the revised manuscript:

      • We used PRX6-Flag as a FLAG-tagged negative control protein in the co-immunoprecipitation experiment, and showed that αSyn-HA was detected in the LDHA-Flag pull-down but not in the PRX6-Flag control pull-down, supporting specificity of the LDHA-associated αSyn signal (Fig 1C).
      • We performed co-immunoprecipitation without crosslinkers in HEK293T cells co-expressing LDHA-Flag and αSyn-HA. In the absence of DSG, αSyn was not detected in LDHA-Flag immunoprecipitates )Supp Fig. 2B), suggesting that the LDHA-αSyn association is not efficiently preserved under conventional lysis and immunoprecipitation conditions. We envision that the αSyn-LDHA complex requires the intact cellular setting to remain a complex, and DSG preserves this setting.
      • We performed a proximity ligation assay (PLA; [31]) in intact HEK293T cells and in intact mouse primary hippocampal neurons.
      • HEK293T cells: Using antibodies against LDHA and aSyn, we detected a high PLA signal in aSyn-expressing cells, and a very low signal in vector control cells (Supp Fig. 2C).
      • Mouse primary hippocampal neurons: Using antibodies against LDHA and aSyn, we detected endogenous LDHA and endogenous αSyn, without tagged protein overexpression, in primary neurons prepared from ICR-SNCA+/+ and C57BL6JHUK-SNCA−/− mice. In this experiment we observed a robust PLA signal in ICR-SNCA+/+ neurons and a very low signal in C57BL6JHUK-SNCA−/− neurons (Supp Fig. 3B, C). Please find below further information about this experiment and our planned future experiments in our reply to Major comment 4.
      • We generated an AlphaFold model of the αSyn-LDHA complex but it did not reach a high enough confidence score, and thus did not include it in the revised manuscript. These new results add important support that aSyn associates with LDHA, but we agree with the reviewer that additional data is needed to confirm direct binding, e.g., AlphaFold-based structural predictions to model potential binding interfaces. Therefore, we revised the wording throughout the manuscript, and we now use “associates with”, “αSyn-associated” and “close proximity” where appropriate, and we avoid using “direct interaction”.

      Changes made:

      We added PRX6-Flag control data in Fig. 1C, non-crosslinked co-IP in Supplementary Fig. 2B, PLA in Supplementary Fig. 2C and Supplementary Fig. 3, and revised the wording throughout the manuscript.

      Major comment 2. Figure 2D shows that preconditioned αSyn-expressing cells exhibit a growth advantage under rotenone treatment, but broader metabolic consequences are absent. How does low-dose rotenone preconditioning impact glycolysis versus OXPHOS? What about lactate secretion or other metabolic readouts? Also, could the authors contextualize these findings against contradictory literature in their Discussion? For example, an old study (doi: 10.1074/jbc.M105326200) reports that both wild-type and mutant αSyn expression exacerbate rotenone-induced mitochondrial membrane potential loss, suggesting αSyn indirectly sensitizes mitochondria to complex I inhibition by endogenous/exogenous stressors in cells.

      Response: We agree with the reviewer that it is important to connect the growth phenotype to metabolic adaptation. In the revised manuscript, we show that αSyn-expressing clones exhibit higher LDHA activity and increased lactate secretion both under basal conditions and after chronic mild-dose (40nM) rotenone treatment. We also added Seahorse analysis under acute and chronic mild-dose rotenone conditions. These data show that chronic mild-dose rotenone treatment abolished mitochondrial respiration in both aSyn- and vector clones (Supp Fig 6). In glycolysis, aSyn clones showed a larger increase in glycolytic capacity as compared to vector clones following chronic mild-dose rotenone treatment (Fig 4A, B).

      Importantly, we also detected differences between the aSyn- and vector clones in glycolytic reserve, which is the value obtained by the subtraction of the glycolysis capacity (max glycolysis) from the basal rate of glycolysis [34]. aSyn–expressing clones preserve high glycolytic reserve following either acute or chronic mild-dose rotenone treatment, whereas similar treatments abolish the glycolytic reserve in vector clones (Fig 4C). These results are consistent with the idea that the presence of aSyn enables cells to continue to proliferate by maintaining the glycolytic energy reserve when mitochondria energy production is abolished.

      Changes made:

      We revised the Results to integrate LDHA activity, lactate secretion, ECAR, glycolytic reserve, and OCR after acute/chronic mild-dose rotenone treatment. Please see the revised Fig. 4 and Supplementary Fig. 6.

      Regarding the reviewer’s request to contextualize our findings against contradictory literature in the Discussion.

      Response: We thank the reviewer for this important suggestion. We have added this reference to the Discussion (Ref 41 in the revised manuscript) and wrote the following paragraph on p. 16: “How do our findings contextualize against contradictory literature? For example, Lee et al reported that aSyn overexpression exacerbates rotenone-induced ATP loss, suggesting that αSyn indirectly sensitizes mitochondria to complex I inhibition by endogenous/exogenous stressors in cells [41]. Our findings challenge this view that αSyn is intrinsically toxic. We demonstrate that aSyn promotes mitohormesis: mild energetic stress induces adaptive bioenergetic remodeling. Based on our findings we propose that αSyn acts as a stress-response protein recruited during increased energetic demand to maintain bioenergetic homeostasis. This response preserves cellular function, whereas repeated demand may exhaust the program, leading to mitochondrial dysfunction, ATP loss, pathological αSyn conversion and cell death.”

      Major comment 3. Figure 4. αSyn clones display elevated basal respiration and maximal respiratory capacity. This phenotype is underexplored and should be integrated earlier rather than sidelined until the Discussion.

      Response: We agree with the reviewer. We revised the Results to more explicitly discuss the observation that αSyn-expressing clones exhibit increased OCR in addition to increased ECAR. We now frame this as evidence that αSyn increases metabolic flexibility and energetic capacity, rather than acting only through a simple shift from OXPHOS to glycolysis. We also added mitochondrial DNA and membrane potential measurements to show that increased respiration is not explained by major changes in mitochondrial DNA content or mitochondria membrane potential. Finally, we added OCR analysis after acute and chronic rotenone exposure, showing that mitochondrial respiration is suppressed by rotenone in both vector and αSyn-expressing clones, supporting the idea that the adaptive advantage under chronic rotenone depends on preserved glycolytic reserve rather than maintained mitochondrial respiration.

      Changes made:

      We revised the Results and Discussion, added Supplementary Fig. 5C, Supplementary Fig. 5D, and Supplementary Fig. 6, and updated the Seahorse Methods section.

      Major comment 4. Considering the relevance of the proposed mechanism for PD, how and would the observed effects hold in neurons? And how certain readouts, e.g. the proliferative advantage observed upon mitohormesis, would apply to post-mitotic neurons? To this end, it would be critical to recapitulate some of the effects in more relevant systems, e.g. patient-derived iPSCs with SNCA multiplications/mutations, αSyn-silenced primary neurons, or through reanalysis of publicly available PD patient datasets.

      Response: We thank the reviewer for raising this important point. In the past six months, we have setup cultures of neurons to begin to address the relevance of our findings for PD.

      As mentioned above, we initially asked whether the association between endogenous LDHA and endogenous aSyn occurs in intact primary neurons. For this purpose, we cultured primary hippocampal neurons derived from ICR )SNCA+/+) mice and from C57BL6JHUK (SNCA−/−) mice (Ref 32 in revised manuscript). We first validated aSyn expression in ICR (SNCA+/+) brain lysates, and its absence from C57BL6JHUK (SNCA−/−) brain lysates, by Western blot analysis using anti-aSyn Abs (Supp Fig 3A). Mouse primary hippocampal neurons prepared from both mouse strains were cultured, and proximity ligation assay (PLA) was performed 12 days-post culture using anti-LDHA and anti-aSyn Abs. This analysis revealed a strong PLA signal in multiple ICR-SNCA+/+ primary neurons, which was largely absent from C57BL6JHUK-SNCA−/− primary neurons (Supp Fig 3B, C). The fact that endogenous aSyn and LDHA associate with each other in neurons argues that this association is likely to be relevant to PD.

      On the other hand, showing that overexpression of aSyn protects neurons from mitochondrial stress was more challenging, and so far, we could not find an experimental setting to demonstrate this. None-the-less, we laid the foundation for a longer-term approach, and we are in the process of expanding C57BL6 SNCA+/+ and SNCA−/− mouse colonies. We envision that these mice, and cultured primary neurons prepared from them, will be the ultimate approach to address the relevance of our findings to PD.

      Minor comment 1. loading control for the Western blot in Figure 1B is missing.

      Response: We thank the reviewer for noting this point. In the revised manuscript, we replaced the original panel with a new subcellular fractionation experiment that more directly addresses the point we intended to make. Specifically, our aim was to determine whether the DSG-cross-linked αSyn-immunoreactive high-molecular-weight (HMW) species are present only in the cytosolic fraction or also in the mitochondria-enriched heavy membrane fraction. To this end, cells from the aSyn-clone #2 were treated with DSG and then subcellularly-fractionated into the cytosolic S100 and the mitochondria-enriched heavy membrane fractions. The results show that both p17-aSyn and the HMW-cross-linked aSyn-immuno-reactive bands/complexes are detected only in the cytosolic S100 fractions (Fig 1B). These results are consistent with the idea that the HMW-cross-linked aSyn-immuno-reactive bands/complexes detected in whole cells are comprised of cytosolic protein(s).

      Changes made:

      We revised Fig. 1B and the corresponding figure legend.

      Minor comment 2. "P17-αSyn" abbreviation (intro, page 6) has never been introduced nor explained.

      Response: We thank the reviewer for pointing this out. We revised the text to introduce this notation clearly as the monomeric approximately 17-kDa αSyn band. Where possible, we also simplified the wording to “monomeric αSyn” to avoid unnecessary confusion.

      Changes made:

      We revised the Results to clarify the meaning of p17-αSyn.

      Minor comment 3. Labels in figures are sometimes not properly explained, e.g., shades of red for aSyn clones in Figures 3 and 4 are not keyed to specific clones.

      Response: We thank the reviewer for this helpful comment. We revised the figures to include a separate legend for each clone, better explain the clone labeling and experimental groups.

      Changes made:

      We revised Figures 3A, 3D, 4A, 5A and 6 to include each clone separately.

      PeerReviewed
    2. EMBOpress 08 Aug 2026

      Note: This preprint has been reviewed by subject experts for Review Commons. Content has not been altered except for formatting.

      Learn more at Review Commons

      Referee #3

      Evidence, reproducibility and clarity

      In this manuscript the authors aim to further elucidate the physiological role of aSyn, a protein highly enriched at synaptic terminals that supports key neuronal functions and contributes prominently to Parkinson's disease (PD) pathology when SNCA gene mutations alter/ increase its expression. Based on previous accounts that a) monomeric aSyn alone is not sufficient to promote PD pathology in vivo and b) α-syn can exert cytoprotective effects during oxidative stress or provide neuroprotection in hypoxia-challenged mice when overexpressed, the authors seek to uncover α-syn's metabolic functions.

      Using HEK293T stable clones expressing aSyn and exposed to the complex I inhibitor rotenone, the authors provide evidence that aSyn expression enhances LDHA activity, boosts mitochondrial respiration, and lowers mitochondrial ROS levels. Interestingly, pre-treatment of HEK293T with rotenone discloses a mito-hormetic effect of aSyn which confers a proliferative advantage over control cells. Based on these data the authors conclude that aSyn functions as a metabolic rheostat enabling cells adaptation during stress. While these findings suggest a novel role for aSyn in metabolism with potential implications for PD pathology, stronger mechanistic evidence is needed. Critically, despite aSyn's central role in PD, the study provides no data demonstrating relevance in neuronal cells.

      Major points:

      • Figure 1C: The co- IP lacks important controls, such as cells expressing an empty vector or a FLAG-tagged non-interacting control protein (e.g., cytosolic GFP-FLAG). Also, IP alone does not sufficiently support a direct interaction between aSyn and LDHA. While co-association in a complex is evident, additional data are needed to confirm direct binding, e.g., AlphaFold-based structural predictions to model potential binding interfaces.

      • Figure 2D shows that pre-conditioned aSyn-expressing cells exhibit a growth advantage under rotenone treatment but broader metabolic consequences are absent. How does low-dose rotenone preconditioning impact glycolysis vs OXPHOS? What about lactate secretion or other metabolic readouts? Also, could the authors contextualize these findings against contradictory literature in their Discussion? For example, an old study (doi: 10.1074/jbc.M105326200) reports that both wild-type and mutant aSyn expression exacerbate rotenone-induced mitochondrial membrane potential loss, suggesting aSyn indirectly sensitizes mitochondria to complex I inhibition by endogenous/exogenous stressors in cells.

      • Figure 4. All aSyn clones display elevated basal respiration and maximal respiratory capacity, adding complexity to the narrative of aSyn as direct interactor of LDHA, and leaving also this phenotype rather underexplored: what does it imply for mitochondrial function or bioenergetics? Along these lines, this aSyn-driven increased mitochondrial respiration is introduced but sidelined until the Discussion section, where it's framed as aSyn boosting "overall energetic capacity." This aligns better with the data than overemphasizing LDHA/glycolysis, and I would suggest the authors to integrate and discuss this earlier in the manuscript.

      • Considering the relevance of the proposed mechanism for PD, how and would the observed effects hold in neurons? And how certain readouts, e.g. the proliferative advantage observed upon mitohormesis, would apply to post-mitotic neurons? To this end, it would be critical to recapitulate some of the effects in more relevant systems, e.g. patient-derived iPSCs with SNCA multiplications/mutations, aSyn-silenced primary neurons, or through reanalysis of publicly available PD patient datasets.

      Minor points:

      • A loading control for the Western blot in Figure 1B is missing.

      • "P17-aSyn" abbreviation (intro, page 6) has never been introduced nor explained.

      • Labels in figures are sometimes not properly explained, e.g., shades of red for aSyn clones in Figures 3 and 4 are not keyed to specific clones.

      Significance

      The study proposes a novel metabolic role for aSyn via LDHA/glycolysis modulation which the authors suggest is relevant for OXPHOS-dependent neurons (as also stated at page 16 in the Discussion), but the study requires additional work to substantiate their proposed model, and the exclusive use of HEK293 cells limits the translational impact of the study.

      Audience: basic research.

      Expertise: mitochondrial metabolism, cellular neuroscience, neurodegeneration

      PeerReviewed
    3. EMBOpress 08 Aug 2026

      Note: This preprint has been reviewed by subject experts for Review Commons. Content has not been altered except for formatting.

      Learn more at Review Commons

      Referee #2

      Evidence, reproducibility and clarity

      In their contribution, Geul et al. found that chronic overexpression of a-synuclein (aSyn) in human embryonic kidney (HEK293) cells shifts cellular metabolism towards increased glycolysis AND simultaneously increased oxidative phosphorylation (OxPhos). These changes correlated with a proposed interaction of aSyn and lactate dehydrogenase A (LDHA). aSyn is the key component of Lewy bodies, the histopathological hallmark of Parkinson's disease (PD) and aSyn mutation and increased gene dosage causes PD which makes the project scientifically interesting. Previous work has apparently found that shifting metabolism of dopaminergic neurons, which degenerate in PD, towards glycolysis has some protective effect. However, the work has several substantial flaws.

      • For one, the proposed interaction of LDHA and aSyn was only studied by coimmunoprecipitation of tagged and crosslinked proteins after massive transient overexpression in HEK cells. As HEK cells only express very low and negligible amounts of endogenous aSyn this overexpression probably results in vast amounts of mislocalized aSyn. No attempts are described to verify this interaction in a more relevant cellular model with endogenous proteins. I would ask for native co-immunoprecipitation with and without crosslinking and proximity ligation assays from at least something like SH-SY5Y cells which express endogenous aSyn.

      • aSyn was expressed with an IRES-GFP but the control contained only GFP which is not ideal It is unclear why rotenone results in increased levels of aSyn. Less degradation, increased expression? At least a qPCR could help.

      • For the claim that aSyn overexpression shifts metabolism towards increased glycolysis and OxPhos important controls are missing. What about cell numbers, mito mass, mitochondrial membrane potential etc. Were these experiments done with or without rotenone preconditioning?

      • MitoSox measures mitochondrial hydrogen peroxide and not mitoROS

      Significance

      I have my doubts whether the reported findings are relevant for the understanding of aSyn physiology and aSyn-caused PD.

      My expertise is in mitochondrial dysfunction and neurodegeneration. I feel well qualified in assessing this work.

      PeerReviewed
    4. EMBOpress 08 Aug 2026

      Note: This preprint has been reviewed by subject experts for Review Commons. Content has not been altered except for formatting.

      Learn more at Review Commons

      Referee #1

      Evidence, reproducibility and clarity

      Geula et al seek insight into the physiological function of a-synuclein in the context of cell metabolism. Misfolded and aggregated form of a-synuclein in neurodegeneration has been a major focus of research but less is known about the function of the physiological monomeric form. The Authors created a stable a-synuclein overexpression in HEK and demonstrated interaction of a-synuclein with LDHA with increased lactate production and decreased ROS production. They also show that a-synuclein overexpressing cells have favorable response to mild and prolonged complex I inhibition in terms of metabolic adaptation and survival. The Authors conclude that a-synuclein has a role in metabolic adaptation during prolonged mitochondrial stress. It is an interesting study and a well written ms.

      The following points need consideration:

      • Overexpression of a-synuclein does not seem to affect cell growth but is its level in the range that might occur in living organisms? Protein protein interactions of a-synuclein are shown under treatment with supramaximal complex I inhibition. To show relevance of the interaction in resistance to prolonged and mild complex I inhibition (40nM rotenone), it would be important to show the protein complexes under those conditions.

      • Would it be possible to test the physiological relevance of a-synuclein by siliencing/knockout strategy?

      • Table 1 is difficult to understand and is not explained well by the legend. Fig2A scale bar 20uM has to be changed to 20um.

      Significance

      I am expert in mitochondrial biology

      PeerReviewed
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    Alfredo Saad-Filho & Jack Taggart | Defense Dividends
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    1. mrchrisadams 08 Aug 2026
      The relationship between finance, technology, and war is of course not new. Bond markets first emerged in Britain in the seventeenth century to finance war with France.

      Wow, I had no idea this was where bonds came from!

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    Quantifying the contribution of genetic variation to healthcare expenditure across diverse healthcare systems
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    1. NBSecon144 08 Aug 2026

      The GWAS association of genotypes with healthcare costs is of great interest. However, it is unclear that “quantifying expenditure associated with pathogenic variants or elevated polygenic risk can inform the cost-effectiveness of screening and other interventions.” Observational cost estimates reported in the paper reflect average healthcare use for individuals with and without clinical diagnoses and with or without the adoption of prevention strategies. The paper states, “we estimate that BRCA2 loss-of-function carriers alone account for an additional €17.4 million (£15.1 million) in annual inpatient costs. Importantly, these estimates capture cumulative healthcare expenditures incurred across conditions and over time, rather than costs attributable to a single cancer diagnosis. As such, they provide empirically grounded inputs for decision-analytic models, including those evaluating screening and preventive interventions, which often rely on simplified assumptions about disease incidence or treatment costs.”

      However, a cost-effectiveness model of screening needs to model expected costs with and without diagnoses established through screening. Average costs for individuals with BRCA1/2 variants relative to individuals with other genotypes does not indicate how costs change with earlier diagnosis and management.

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    medrxiv.org/content/10.64898/2026.07.14.26358031v1
  45. agenda.community agenda.community
    Tags, People, Emoji's, Text Actions and Links - How To - Agenda Community
    1
    1. Fradeet 08 Aug 2026
      Most tags are simple labels, but it is possible to use parameters within tags. For example, you could use the tag importance with different parameters for each level of importance. So one piece of text might contain the tag #importance(low), and another #importance(high).

      Bulid nest-like tags.

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    agenda.community/t/tags-people-emojis-text-actions-and-links/61
  46. www.thenerve.news www.thenerve.news
    Cory Doctorow: The people who tell you ‘AI is changing everything’ are lying
    1
    1. parmoset 08 Aug 2026
      These businesses aren't just wasting billions – they're replacing skilled workers with defective chatbots. As I've written before, AI is the asbestos we're shovelling into the walls of our technological society. Our descendants will spend generations digging it out again, and the longer the bubble goes on without popping, the longer it will take to repair the damage.
      AI hype quotes
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    thenerve.news/p/cory-doctorow-ai-business-incentive-to-lie-useless-chatbots-report-nikhil-suresh
  47. www.biorxiv.org www.biorxiv.org
    HiExM Enables Scalable Mapping of Organelle Morphology and Spatial Heterogeneity
    1
    1. prachee.avasthi 08 Aug 2026

      Curious whether you could try label-free imaging, such as quantitative phase or SRS as an orthogonal assessment of organelle morphology. Maybe a coarse-grained measurement pre-expansion could be compared with the expanded sample to check marker dependence without requiring CLEM. Alternatively, do you have a sense of whether intrinsic contrast with either modality would survive expansion to allow label-free imaging of the expanded sample itself?

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    biorxiv.org/content/10.64898/2026.07.12.738053v1
  48. agentfactory.panaversity.org agentfactory.panaversity.org
    AI Prompting in 2026: A Crash Course | The AI Agent Factory
    5
    2. ali_ahmad 08 Aug 2026
      evers

      A lever is something you can pull to change the result. For example: “A robot in a city.” v/s “A cinematic cyberpunk robot in a neon-lit futuristic city, low-poly, dramatic lighting.”

      You're essentially pulling different visual levers

    5. ali_ahmad 08 Aug 2026
      AI sees images coarsely.

      coarse understanding means big picture understand. AI can understand the the overall scene of picture and is good at this but it is weak at understading the fine(specific/small) details. E.g: Coarse understanding: “I see a car.”

      Fine understanding: “It's a 2024 Toyota Corolla, white, with a specific license plate number.”

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    agentfactory.panaversity.org/docs/ai-prompting-2026
  49. agenda.community agenda.community
    Text Actions Cheat Sheet - How To - Agenda Community
    4
    2. Fradeet 08 Aug 2026
      Actions in Agenda allows you to type short commands that upon completion get dynamically converted and expanded into plain text, or invoke a certain action like marking a note as On the Agenda.

      Do most actions without mouse (cursor).

    3. Fradeet 08 Aug 2026
      Similarly, on some keyboards, like the Chinese or Japanese ones, it’s hard to type a backslash character, therefore wherever a backslash character is shown, you can also use two backticks (``) or two middle-dot characters (··).

      If you use IME, can use this replace \.

    4. Fradeet 08 Aug 2026
      On iPhone and iPad without a hardware keyboard, typing the backslash character can be a bit cumbersome. Instead you can simply tap-and-hold the plus button above the keyboard to trigger the action menu. Handy!

      Hold 'plus' button on iOS to use Text Actions.

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    agenda.community/t/text-actions-cheat-sheet/86794/2
  50. www.axios.com www.axios.com
    AI labs can't keep their stars
    1
    1. parmoset 08 Aug 2026
      A source familiar told Axios that Anthropic CEO Dario Amodei has expressed concern about new talent coming to the firm for the money rather than the mission.

      Oh really??? Poor Dario. Maybe he could give up his salary first to set an example.

      As @nixCraft@mastodon.social said: "So he steals every info out there and now he wants people to come and work free for him?" https://mastodon.social/@nixCraft/117033260617630492

      See also: https://finance.yahoo.com/technology/ai/articles/anthropic-ceo-reportedly-worried-hires-160000647.html

      AI
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  51. pressbooks.online.ucf.edu pressbooks.online.ucf.edu
    Introduction
    1
    1. brueckner 08 Aug 2026
      In Gravitation(opens in new tab), we examined the force of gravity, which acts on all objects with mass. In this chapter, we begin the study of the electric force, which acts on all objects with a property called charge. The electric force is much stronger than gravity (in most systems where both appear), but it can be a force of attraction or a force of repulsion, which leads to very different effects on objects. The electric force helps keep atoms together, so it is of fundamental importance in matter. But it also governs most everyday interactions we deal with, from chemical interactions to biological processes.

      A good intro blurb, comparing the gravitational interaction,

      $$\vec{F}\left(r\right)=-\frac{G m_1 m_2}{r^2}\hat{r}$$

      to the Coulomb interaction,

      $$\vec{F}\left(r\right)=\frac{k q_1 q_2}{r^2}\hat{r}$$

      in which \(\hat{r}\) points from object #1 toward object #2.

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    pressbooks.online.ucf.edu/uphysicstjb/chapter/introduction-5/
  52. tesda-course.pages.dev tesda-course.pages.dev
    Lesson 15 · Prepare a numerical recommendation and explain it — TESDA Foundational Skills
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    tesda-course.pages.dev/build/num-2b-l15
  53. tesda-course.pages.dev tesda-course.pages.dev
    Lesson 14 · Verify accuracy and choose the best option — TESDA Foundational Skills
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    tesda-course.pages.dev/build/num-2b-l14
  54. tesda-course.pages.dev tesda-course.pages.dev
    Lesson 13 · Examine variables to find patterns and summarize — TESDA Foundational Skills
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    tesda-course.pages.dev/build/num-2b-l13
  55. tesda-course.pages.dev tesda-course.pages.dev
    Lesson 12 · Organize and connect data from multiple sources — TESDA Foundational Skills
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    tesda-course.pages.dev/build/num-2b-l12
  56. tesda-course.pages.dev tesda-course.pages.dev
    Lesson 11 · Estimate to check a result before recording it — TESDA Foundational Skills
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    tesda-course.pages.dev/build/num-2b-l11
  57. tesda-course.pages.dev tesda-course.pages.dev
    Lesson 10 · Solve a routine workplace problem end to end — TESDA Foundational Skills
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  58. tesda-course.pages.dev tesda-course.pages.dev
    Lesson 9 · Apply shape properties to a practical problem — TESDA Foundational Skills
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    tesda-course.pages.dev/build/num-2b-l9
  59. tesda-course.pages.dev tesda-course.pages.dev
    Lesson 8 · Convert between common units for a task — TESDA Foundational Skills
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  60. tesda-course.pages.dev tesda-course.pages.dev
    Lesson 7 · Use measuring tools and apply units on the job — TESDA Foundational Skills
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    tesda-course.pages.dev/build/num-2b-l7
  61. tesda-course.pages.dev tesda-course.pages.dev
    Lesson 6 · Build a simple formula, then calculate with it — TESDA Foundational Skills
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    tesda-course.pages.dev/build/num-2b-l6
  62. tesda-course.pages.dev tesda-course.pages.dev
    Lesson 5 · Interpret a simple algebraic expression — TESDA Foundational Skills
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    tesda-course.pages.dev/build/num-2b-l5
  63. tesda-course.pages.dev tesda-course.pages.dev
    Lesson 4 · Describe patterns and trends in workplace data — TESDA Foundational Skills
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    tesda-course.pages.dev/build/num-2b-l4
  64. drive.google.com drive.google.com
    DESENVOLVIMENTO PESSOAL E ORGANIZACIONAL - Google Drive
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    drive.google.com/drive/folders/1eD_S55U8eNAMdN8NxyE_CMlSvJFQb-2E
  65. tesda-course.pages.dev tesda-course.pages.dev
    Lesson 3 · Explain relationships between numerical values — TESDA Foundational Skills
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    tesda-course.pages.dev/build/num-2b-l3
  66. tesda-course.pages.dev tesda-course.pages.dev
    Lesson 2 · Recall measurement units and conversion facts — TESDA Foundational Skills
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    tesda-course.pages.dev/build/num-2b-l2
  67. tesda-course.pages.dev tesda-course.pages.dev
    Lesson 1 · Name the parts of tables, charts, and graphs — TESDA Foundational Skills
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    tesda-course.pages.dev/build/num-2b-l1
  68. simata.sttkd.ac.id simata.sttkd.ac.id
    22021859002.pdf
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    simata.sttkd.ac.id/uploads/logbook/22021859/22021859002.pdf
  69. freakonometrics.github.io freakonometrics.github.io
    Introduction — The Price Assigned to Us – Risk-Priced Society
    1
    1. ChristianOy 08 Aug 2026
      should not

      What is the nature of this obligation? Is it moral, philosophical, political, economic, etc.? Who defines its terms, or who should? What is the position of each stakeholder? Do these questions call for the same answers depending on the nature of the risk?

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    freakonometrics.github.io/risk-priced-society/en/chapters/introduction.html
  70. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    LRRK2 regulates synaptic function through modulation of actin cytoskeletal dynamics
    2
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    pmc.ncbi.nlm.nih.gov/articles/PMC13446905/
  71. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Pink1-mediated mitophagy in the endothelium releases proteins encoded by mitochondrial DNA and activates neutrophil responses during inflammation
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    pmc.ncbi.nlm.nih.gov/articles/PMC13423353/
  72. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    In-cell cryo-electron tomography reveals differential effects of type I and type II kinase inhibitors on LRRK2 filament formation and microtubule association
    1
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    pmc.ncbi.nlm.nih.gov/articles/PMC13405622/
  73. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Excitatory cholecystokinin neurons in the CA3 area regulate the navigation learning and neuroplasticity
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    pmc.ncbi.nlm.nih.gov/articles/PMC13412322/
  74. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    MTUS2-AS1 suppression promotes DDX5 protein degradation to enhance the sensitivity of PARP inhibitors in BRCA-wild triple negative breast cancer
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    pmc.ncbi.nlm.nih.gov/articles/PMC13412408/
  75. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Targeting of ELMO2 by the Shigella E3 Ligase IpaH4.5 Reveals Key Differences Between ELMO Paralogs
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    pmc.ncbi.nlm.nih.gov/articles/PMC13419521/
  76. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Spatial control of mitochondrial retrograde signaling by nuclear pore-associated contact sites
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    pmc.ncbi.nlm.nih.gov/articles/PMC13419819/
  77. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Extended amygdala orchestrates social motivation in socially isolated mice
    7
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    pmc.ncbi.nlm.nih.gov/articles/PMC13419728/
  78. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Metabolic engineering of Escherichia coli to modulate hydrogen sulfide levels in the mammalian gut
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    pmc.ncbi.nlm.nih.gov/articles/PMC13419456/
  79. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Mesohabenular glutamatergic regulation of the consequences of uncontrollable stress
    5
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    pmc.ncbi.nlm.nih.gov/articles/PMC13419501/
  80. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    The HIV-1 restriction factor RPRD2 does not inhibit transcription of HIV-1 or endogenous retroelements
    3
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    pmc.ncbi.nlm.nih.gov/articles/PMC13419777/
  81. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Psi RNA-specific Binding Promotes HIV-1 Gag Conformational Change Critical for Immature Viral Particle Assembly
    1
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    pmc.ncbi.nlm.nih.gov/articles/PMC13420455/
  82. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    SGEF coordinates epithelial morphogenesis by regulating junction stability, collective migration, and extracellular matrix remodeling
    3
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    pmc.ncbi.nlm.nih.gov/articles/PMC13419416/
  83. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    A machine learning model predicts protein stability of annotated and alternate protein isoforms
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    pmc.ncbi.nlm.nih.gov/articles/PMC13404906/
  84. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Psychedelic drug action at dendrites is gated by behavioral state and serotonin receptors
    2
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    pmc.ncbi.nlm.nih.gov/articles/PMC13419809/
  85. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    The Disease Gene THAP12 is a Transcriptional Regulator of Mitochondrial ETC Complex I
    1
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    pmc.ncbi.nlm.nih.gov/articles/PMC13404843/
  86. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Integrated Interactomics Reveals Novel Protein Associations: The FOXA1-PBX1 Complex as a Case Study
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    pmc.ncbi.nlm.nih.gov/articles/PMC13404648/
  87. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Unique mushroom spine morphology signature in cocaine relapse ensembles in rat nucleus accumbens core
    2
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    pmc.ncbi.nlm.nih.gov/articles/PMC13419704/
  88. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Projectomic Organization of the Serotonin System of the Mouse Brain
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    pmc.ncbi.nlm.nih.gov/articles/PMC13404724/