Here are the major points summarizing the text on globin gene clusters and hemoglobin:

Globin Gene Clusters:

• Globin is encoded in two nonallelic gene clusters: β-globin gene cluster on chromosome 11 and α-globin gene cluster on chromosome 16.
• The β-globin gene cluster contains an embryonic ε-globin gene, two fetal γ-globin genes, a major adult β-globin gene, and a minor adult δ-globin gene.
• The α-globin gene cluster contains an embryonic ζ-globin gene and duplicated α-globin genes with identical proteins.
• Hemoglobin production begins with embryonic hemoglobins: Gower I, Gower II, Portland I, and Portland II.
• Fetal hemoglobin (HbF) production starts at 6-8 weeks of gestation, peaks during mid-gestation, and falls to <1% of total hemoglobin during the first 6 months of extrauterine life.
• Adult hemoglobin A (HbA) production follows a pattern reciprocal to that of HbF.
• Hemoglobin composition of normal adults is >95% HbA, ~1% HbF, and 2-3% HbA2.
• Hemoglobin is subject to posttranslational modifications, the most important being the nonenzymatic glycosylation of HbA forming the adduct HbA1c.

Hemoglobin Structure:

• All globin polypeptides have similar but not identical primary structures. α-Globins contain 141 amino acids, and β-like globins have 146 amino acids.
• The primary structure dictates the secondary structure of globin into α-helical sections joined by small nonhelical stretches.
• Each globin chain folds into a tertiary conformation known as the globin fold, where charged amino acid residues face the exterior of the molecules and uncharged residues face the hydrophobic interior.
• The iron-containing tetrapyrrole heme moiety is protected from oxidation and located between two of the helical segments; O2 loading and unloading occur when heme iron is in its reduced ferrous form.
• Globin gene mutations affecting critical heme-binding amino acid residues allow iron to be oxidized, forming methemoglobin, which has high O2 affinity and does not release O2 in tissues.
• Dimers of α- and non-α-globin chains reversibly assemble into tetramers, forming a quaternary structure.

Hemoglobin Function:

• Hemoglobin transports O2 from lungs to tissues and carbon dioxide (CO2) from tissues to lungs.
• Hemoglobin is a nitrate reductase that releases nitric oxide (NO) from nitrite to promote vasodilation.
• Oxygen binding is defined by the sigmoidal shape of the hemoglobin-O2 dissociation curve.
• The P50 is a point on this curve that indicates the partial pressure of O2 where hemoglobin is half saturated.
• The P50 is influenced by the binding of 2,3-bisphosphoglycerate, pH, and temperature.
• The conformation of hemoglobin fully saturated with O2 is known as the R or relaxed state; desaturated hemoglobin is in the T or tense state.
• Hemoglobin variants that decrease P50 are characterized by isolated erythrocytosis as compensation for hypoxia.
• Variants with increased P50 sometimes are accompanied by cyanosis and anemia as hemoglobin becomes unsaturated and O2 delivery is enhanced.
• Mutations of residues critical for heme binding, R-T transitions, or tetramer stability cause hemoglobinopathies characterized by hemolytic anemia

summary Oropharyngeal Dysphagia: - Poor bolus formation and control, drooling, and difficulty initiating swallowing are characteristic signs. - May result in premature spillage of food into the hypopharynx, aspiration into the trachea, or regurgitation into the nasal cavity. - Causes include neurologic, muscular, structural, iatrogenic, infectious, and metabolic factors, with iatrogenic, neurologic, and structural pathologies being the most common. - Iatrogenic causes include head and neck cancer treatments such as surgery and radiation. - Neurogenic dysphagia resulting from cerebrovascular accidents, Parkinson’s disease, and amyotrophic lateral sclerosis is a major cause of morbidity related to aspiration and malnutrition. - Asymmetry in the cortical representation of the pharynx provides an explanation for the dysphagia that occurs as a consequence of unilateral cortical cerebrovascular accidents. - Structural lesions causing dysphagia include Zenker’s diverticulum, cricopharyngeal bar, and neoplasia. - Rapid-sequence fluoroscopy is necessary to evaluate for functional abnormalities. - Adequate fluoroscopic examination requires that the patient be conscious and cooperative. - Timing and integrity of pharyngeal contraction and opening of the UES with a swallow are analyzed to assess both aspiration risk and the potential for swallow therapy. - Structural abnormalities of the oropharynx should be assessed by direct laryngoscopic examination.

Esophageal Dysphagia: - The adult esophagus measures 18-26 cm in length and is anatomically divided into the cervical esophagus and the thoracic esophagus. - Solid food dysphagia becomes common when the lumen is narrowed to <13 mm. - The most common structural causes of dysphagia are Schatzki’s rings, eosinophilic esophagitis, and peptic strictures. - Propulsive disorders leading to esophageal dysphagia result from abnormalities of peristalsis and/or deglutitive inhibition, potentially affecting the cervical or thoracic esophagus. - Rapid-sequence fluoroscopy is necessary to evaluate for functional abnormalities. - Adequate fluoroscopic examination requires that the patient be conscious and cooperative. - High-resolution manometry is used to measure pressure changes along the length of the esophagus during swallowing. - Structural abnormalities of the esophagus should be assessed by endoscopic examination.

Here's a table summarizing the information:

| Category | Oropharyngeal Dysphagia | Esophageal Dysphagia | | --- | --- | --- | | Signs and Symptoms | Poor bolus formation and control, drooling, difficulty initiating swallowing | Solid food dysphagia, potentially accompanied by altered esophageal sensation, reduced distensibility, or motor dysfunction | | Causes | Neurologic, muscular, structural, iatrogenic, infectious, metabolic | Structural causes include Schatzki’s rings, eosinophilic esophagitis, and peptic strictures; propulsive disorders due to abnormalities of peristalsis and/or deglutitive inhibition | | Iatrogenic Causes | Head and neck cancer treatments such as surgery and radiation | N/A | | Diagnosis | Rapid-sequence fluoroscopy, direct laryngoscopic examination | Rapid-sequence fluoroscopy, high-resolution manometry, endoscopic examination |

1. Iron is transported in the blood by the iron-transferrin complex.
2. The complex interacts with specific transferrin receptors on the surface of cells that express transferrin receptors, such as developing erythroblast cells.
3. The iron-bearing transferrin is internalized via clathrin-coated pits and transported to an acidic endosome.
4. Iron is released from the transferrin at the low pH of the endosome.
5. Iron is made available for heme synthesis.
6. The transferrin-receptor complex is recycled to the surface of the cell.
7. The bulk of the transferrin is released back into circulation, and the transferrin receptor re-anchors into the cell membrane.
8. Iron in excess of the amount needed for hemoglobin synthesis binds to a storage protein, apoferritin, forming ferritin.
9. Senescent red cells are recognized by the cells of the reticuloendothelial system and undergo phagocytosis.
10. Hemoglobin is broken down, and the iron is shuttled back to the surface of the RE cell.
11. Iron is presented to circulating transferrin via the iron export channel, ferroportin.
12. Iron is then available for reutilization for hemoglobin synthesis

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This entire comment is gold

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Seelbinder et al. describe a new method for perturbing chromatin in living cells by local heating. Employing this approach, the authors uncover interesting behaviors that underscore the variability in the mechanical response of subnuclear domains and structures. The study is timely, and if some conceptual and technical aspects are improved, it should be of broad interest to both the cell biophysics and cell biology communities, in particular since the method can also be applied to study mechanical relationships of subcellular compartments in other cellular and multicellular systems.

eLife assessment

This study presents a useful inventory of chromatin modifications and genes that are up- and down-regulated during cerebellar development in vivo and in primary culture. The main claims were incomplete and would benefit from further analysis and/or additional experiments. The work will be of interest to biologists working on brain development.

eLife assessment

This study presents important findings regarding the quantification of dynamics in fish communities in changing ecosystems by combining a large-scale environmental DNA metabarcoding time series with novel statistical approaches. The methods are convincing, with controlled experiments, thorough statistical analyses, and a substantial dataset covering two years of detailed observation, which can provide sufficient power to detect fine-scale ecological interactions. This work is relevant for informing future research on assessing community stability under climate change.

eLife assessment

The authors use a combination of structural and MD simulation approaches to characterize phospholipid interactions with the pentameric ligand-gated ion channel, GLIC. The general agreement between structures and simulations increases confidence in the description of the lipid interaction poses, and provides a solid basis for the prediction of a state dependent interaction site where lipids could dynamically modulate channel gating. The results will be very useful to understand the nature of phospholipid interactions with pentameric ligand-gated ion channels, although the functional or structural significance of these lipid interactions remains unclear.

eLife assessment

This interesting study builds on previous work by the PI implicating Greatwall/MASTLKinase in recovery from DNA damage in cultured human cells. This study identifies a ubiquitin ligase that may regulate the stability of Greatwall/MASTL protein stability, and the authors propose that this constitutes a molecular "timer" that controls recovery from DNA damage. Should this be validated it would be an important advance for the field, but the data presented are currently incomplete and do not yet fully support this claim.

eLife assessment

The authors have uncovered a new target that may be exploited to selectively kill BRCA2 mutant cancer cells. Strengths of the study include the novel pathway uncovered (ROCK kinases) and the strong data in support of the findings. Weaknesses include limited detail regarding the mechanism of BRCA2-specific cell death by ROCK kinase inhibitors, limited information on why some ROCK kinase inhibitors are not effective, as well as whether the cell killing in BRCA2 wild-type cells by ROCK kinase inhibitors is the same mechanism but just attenuated. The work will be of interest to cancer biologists and colleagues studying kinases.

eLife assessment

This manuscript is of interest to readers in the field of neural development. The study is important as it examines two mutations within a homeodomain transcription factor called Cone-Rod Homeobox (CRX) that cause retinopathy in humans. The data are solid, and the work contributes to our understanding of the underlying pathogenetic mechanisms.

eLife assessment

This study combines experiments in developing embryos and embryo extracts to investigate a fundamental relationship in biology - how the size of mitotic chromosomes scales with changes in cell size during development. By combining the unique tools available in the Xenopus system with modern genomic approaches, the authors convincingly demonstrate that mitotic chromosome scaling is mediated by differential loading of maternal chromatin remodeling factors during interphase. Although it remains unclear exactly how these factors impact chromosome size, the findings reported here will be of broad interest to the cell biology community and are likely to spawn new avenues of experimental inquiry aimed at understanding intracellular scaling relationships.

eLife assessment

This study provides important estimates from international cancer screening data repository about the impact of the COVID-pandemic related disruptions on cancer screening programs in selected low- and middle-income countries. The evidence supporting the study is solid and relies on national-level screening program attendee volumes and assessments of screen positives during 2019 (pre-pandemic) and 2020 (during the pandemic). The study provides real-world data estimates of proportions/volumes of missed screenings due to pandemic control measures (lockdowns and closures) and may contribute to future modelling efforts for measuring the impact on late/advanced stage detection and excess case burden and mortality.

eLife assessment

This paper addresses an important clinical concern which is how the antidepressant ketamine exerts its effects acts rapidly. The authors suggest the reason is that ketamine increases glutamatergic transmission in the hippocampus. The strengths are the data are mostly very good, and the limitations are a lack of compelling evidence that the hippocampus is the location where effects occur, as well as several other issues.

eLife assessment

This important study will be of interest to those working on mycobacterial signal transduction. A combination of experiments provides convincing evidence to show how universal stress proteins bind to cAMP and function by direct sequestration of the second messenger. Although the methods, data and analyses broadly support the conclusions, the main claims are only partially supported and can be strengthened through further analytic approaches.

eLife assessment

Villalobos-Cantor et. al. describe a new technique for cell-type specific in vivo labeling of nascent peptides, which they call POPPi. POPPi is based on sequence-independent incorporation of the puromycin analog OPP into an elongating peptide, which also simultaneously terminates the growing peptide. To achieve cell-type-specific labeling, the authors used an OPP derivative, PhAc-OPP, as the labeling substrate. The method is potentially interesting but needs further characterization to be able to assess its use.

eLife assessment

This important study combines a screen of known N6-methyladenine (m6A)-dependent RNA modifying factors to identify ALKBH5 as critical in crush injury response. They demonstrate through gain and loss of function an effect on ALKBH5 m6A-dependent Lpin2 mRNA stability during injury-induced axon regeneration in both dorsal root ganglia nerve and optic nerve regeneration. The results provide new insight into the role of RNA modification on neural injury. However, the limitations of the experimental design on the conclusions drawn require additional consideration. With additional control experiments and further consideration of the limitations, the paper will provide a link between N6-methyladenine and neurotrauma.

eLife assessment

This study describes important results and convincing evidence linking myofibroblast senescence in the aged heart with a pro-arrhythmogenic phenotype. This is in turn related to higher mortality after myocardial infarction in the aged rabbit heart. These constitute important empiric as opposed to detailed findings. They nevertheless will be of interest to clinician scientists studying cardiac function and disease.

eLife assessment

Non-communicable diseases (NCDs) are rising rapidly in urbanizing populations in many parts of the developing world, including in sub-Saharan Africa. Temba and colleagues show important evidence that healthy Tanzanians display a pro-inflammatory phenotype with enrichment of specific immune-metabolic pathways. Dood-derived metabolites were identified as an important driver of inflammation-related molecules. These findings provide solid evidence that the dietary transition that occurs in urbanizing areas in sub-Saharan Africa may contribute significantly to the increased incidence of non communicable diseases in this part of the world.

eLife assessment

This important interdisciplinary study substantially advances our understanding of the prolactin receptor interactions with the membrane lipids and the effect of these interactions on cell signaling. The authors use a combination of state-of-the-art NMR structural analysis, simulations, and cellular assays to provide compelling experimental evidence for protein complexes being regulated by IDR-membrane interactions. The work will be of broad interest to structural biologists and biochemists, and the results presented herein are likely relevant for other non-tyrosine kinase receptors.

eLife assessment

This important study demonstrates that the transcription factor Chinmo is a master regulator that maintains larval growth and development as part of the metamorphic gene network in Drosophila. Chinmo does so in part by regulating Broad expression in imaginal tissues (exemplified in the wing disc) and in a Broad-independent manner in other larval tissues such as the salivary gland. Finally, they demonstrate that the role of Chinmo in promoting larval development is conserved between holometabolous insects and hemimetabolous insects, which lack a pupal stage. The data were collected and analyzed using solid and validated methodology and will be of interest to a broad audience including those interested in development and evolution.

eLife assessment

Using surface micropatterning, optical activation, and theoretical analysis, the authors provide compelling evidence that adjacent cells actively propagate mechanical stress in epithelial tissues. The response of the receiver cell is active and enhanced when the principal stress direction is perpendicular to the orientation of actin fibers. This work is important and a must-read for everybody wanting to understand tissue mechanics.

eLife assessment<br /> <br /> This is an important study that uses the song system in a bird model to understand the transcriptional mechanisms underlying neuronal adaptations to sensory deprivation. The manuscript offers compelling data in support of their hypothesis that these transcriptional changes are related to song plasticity. The work will be of interest to biologists who study neuronal plasticity mechanisms.

eLife assessment

Inferior olivary neurons drive complex spiking activity in Purkinje neurons of the cerebellar cortex, ultimately playing critical roles in controlling motor coordination and plasticity. Using transgenic mice or optogenetic techniques to independently control a major excitatory and inhibitory pathway to the inferior olive, the authors show that the probability and phase of olivary neuron output depend critically on the relative timing of excitation and inhibitory inputs. Network models predict that appropriately timed excitatory and inhibitory input patterns efficiently synchronize larger clusters of inferior olivary neurons, raising the possibility that input timing can gate the output of the motor commands. These valuable findings have the potential to impact the field's understanding of sensorimotor processing, but the strength of evidence is currently incomplete.

eLife assessment

The study provides evidence that the hormone PTH increases bone mass by, at least in part, regulating the factor Zfp467. In turn, Zfp67 controls expression of the receptor for PTH, thus creating a feedback loop that overall augments bone mass. The findings are novel and of potential great interest. Overall, the study is of interest to a broad audience and significant as it unveils a novel feedback loop involving PTH, a critical endocrine regulator of calcium, phosphate, and bone mass.

eLife assessment

This paper describes a new method to investigate Staphylococcus aureus intracellular virulence that has produced important insights into the mechanisms of staphylococcal pathogenesis. The results are convincing and the methodology is state-of-the-art. This paper will be of interest to scientists studying microbial intracellular pathogenesis and cell biology.

eLife assessment

This paper demonstrates the genetic architecture of heart mitochondrial proteome that influences cardiac hypertrophy, using a panel of inbred mouse strains called the Hybrid Mouse Diversity Panel (HMDP). The HDM panel is a very powerful tool to study the genetic basis of various physiological and pathological processes in mice. The authors have used this panel extensively before, and in this paper, they extend their proteomic studies to demonstrate the genetic basis of cardiac hypertrophy. The studies will allow us to better understand the genetics of hypertrophic cardiomyopathy.

eLife assessment

This important study greatly expands our knowledge of the fossil record of Mermithid nematodes, modern members of which are ecologically important parasitoids of arthropods, annelids and mollusks today. The most important finding, convincingly presented, is that mermithids parasitized a number of insect clades in the Cretaceous that they are not known to infect today or in Cenozoic amber. The evidence for a shift in exploited hosts from heterometabolous insects in the Cretaceous to holometabolous ones in the Miocene is solid but could be made exceptional by adding a small quantitative analysis with confidence intervals and bar plots from the data already compiled in the supplementary material; potential collection bias should be addressed as well.

eLife assessment

This fundamental work uses deep neural networks to simulate activity evoked by a wide range of stimuli and demonstrates systematic differences in latent population representations between hearing-impaired and normal-hearing animals that are consistent with impaired representations of speech in noise. While the evidence supporting the conclusions is compelling, additional analyses would facilitate the generalizability of the neural-network approach. The research will be of interest to auditory neuroscientists and computational scientists.

eLife assessment

This manuscript provides valuable data gathered using a new video fluoroscopy method by which movements of artificial joints can be visualized in real time. These solid data add to the understanding of the links between symptoms of unstable joints after total knee replacement and actual joint instability. The paper should be of interest to those who study biomechanics after total joint replacement.

eLife assessment

In this study, Li and al describe valuable insights into the mechanisms underlying sex-differences diet-induced obesity in mice, with a role of macrophage-derived RELMa secretion in female-specific protection. They provide solid evidence for the impact of RELMa signaling in eosinophil recruitment for diet-induced obesity protection in female mice. Single-cell RNA-seq analysis of the stromal vascular fraction of control and RELMa deficient animals methods were used to investigate molecular mechanisms underlying the protection as a powerful method, although the analysis of this data is difficult to evaluate with incomplete methodological information.

eLife assessment

In vertebrates, ciliary motility is powered by axonemal dyneins, known as OADs, tethered to doublet microtubules by a pentameric docking complex including the Armc4 and Calaxin subunits. This valuable study combines zebrafish genetics with cryo-electron tomography to convincingly show that Armc4 plays a critical role in the docking of OAD and that Calaxin stabilizes the molecular interaction. The work will be of interest to those studying the structure and function of the axoneme, and motile cilia in general.

eLife assessment

This important study combines behavior, computational modelling and magnetic resonance spectroscopy to address the question whether age-related declines in learning are driven by declines in working memory or deficiencies of the RL system. The general approach is solid, but the presented evidence to support the papers' main claims could be stronger. With additional analyses and adaptation of the main claims, the paper could be of high interest for researchers in the field of cognitive aging and decision making.

eLife assessment

The authors present a manuscript aiming to understand the mechanism(s) underlying myeloid bias in HSCs, specifically focused on the role of Pcgf1, and therefore PRC1.1, in the regulation of hematopoiesis. This important work is of interest to the community of researchers interested in myeloid differentiation, lineage fate decisions in hematopoietic stem cells, and the molecular mechanisms that contribute to the initiation of myeloid malignancies. The methods are rigorous and the results convincingly support the authors' conclusions.

eLife assessment

This is a valuable paper describing an attempt to reconstruct the evolution of Dicer. Using ancestral reconstruction approaches, the authors carefully examine the biochemical characteristics of reconstructed proteins at various junction points in the animal lineage. They provide solid evidence that the deepest ancestrally reconstructed protein has double-stranded RNA stimulated ATPase activity and that this characteristic was lost along the vertebrate lineage. This paper will be of interest to scientists in the RNA-protein interaction and protein evolution fields.

eLife assessment

The authors have established new formulas to predict maximum oxygen uptake for cyclists and runners based on submaximal exercise testing and anthropometric characteristics. This is an important study with a large and comprehensive dataset, which may be helpful for many exercise labs. The work is convincing, using appropriate and validated methodology in line with the current state-of-the-art, as shown by references to common exercise books.

eLife assessment

In the current manuscript, the authors study the effects of hypoxia or genetic and pharmacologic modulation of the hypoxic pathways on T cells. The findings about T cells sense hypoxia and how hypoxia affects T cell (and CAR T cell) differentiation and function are significant and interesting for the field. The data supporting these findings are mostly robust, yet some questions remain open and some statements seem unsupported by evidence.

eLife assessment

This fundamental work substantially advances our understanding of polymer physics underpinnings of genome folding, organization, and regulation. The conclusions are supported by both convincing computer simulations and analytical theory. The work will be of significant interest to the genome folding community.

eLife assessment

This manuscript will be of interest to scientists in the field of tissue injury and repair. It provides novel molecular mechanisms of a transcription factor, Prrx1, in fibroblast activation following lung injury. Overall, the work suggests that PRRX1 plays a functional role downstream of TGFb1 to elicit some aspects of the fibrotic response and that PRRX1 could represent an important therapeutic target to treat fibrosis. The strengths of this work are the multiple approaches applying human and mouse lung tissue used by the authors to test the role of PRRX1 in lung fibrosis, however, in its current form, major limitations need to be addressed.

eLife Assessment

The study has advanced our mechanistic understanding of lung regeneration. While the importance of regeneration of alveolar capillaries for long response to injury has been long recognized, the regulation of this process has not been well understood. Your study provides novel, comprehensive, and compelling evidence that the expression of the transcription factor Atf3 in alveolar capillary endothelial cells plays a critical role in the regeneration of alveolar capillaries following lung injury.

eLife assessment

This study concerns an important area, that of monoallelic expression, but the study does not provide sufficient information about the candidate regulatory RNA to provide a significant advance over previous work, which should also be discussed in more detail.

eLife assessment

This important study provides convincing evidence that locus coeruleus is activated during visuomotor mismatches. Gain of function optogenetic experiments complement this evidence and indicate that locus coeruleus could be involved in the learning process that enables visuomotor predictions. This study, therefore, sets the groundwork for the circuit dissection of predictive signals in the visual cortex. Loss-of-function experiments would strengthen the evidence of the involvement of locus coeruleus in prediction learning. These results will be of interest to systems neuroscientists.

eLife assessment

The study examines the principles according to which neurons connect to each other in the brain. The authors find that data could be best explained by the homophillic wiring principle where neurons preferentially connect to neurons within overlapping groups. The work will provide a valuable resource to the neuroscience community once analyses are standardized across various datasets included.

eLife assessment

This valuable work advances our understanding of the acoustic features driving the attraction of female mice to male vocalizations. The evidence supporting the conclusions is solid, with well-designed place preference assays and manipulations of male song structure. The work will be of broad interest to neurobiologists and ethologists working on mouse social interactions, auditory processing and communication.

eLife assessment

This manuscript combines cryo-EM and a suite of compelling whole cell and proteoliposome transport assays to establish the mechanism and structure of the full-length human SLC26A6 chloride/bicarbonate exchangers, including the first partial view of the previously unresolved IVS region of an SLC26 STAS domain. In combination with prior studies on additional SLC26 paralogs, including the SLC26A9 paralog initially reported by the same group, the current study provides important insight into the mechanistic diversity of the SLC26 transporters. This study is of interest to the biophysics community and the field of membrane transport.

eLife assessment

This study evaluated how naturalistic behaviors are encoded in the striatum by analyzing neural ensembles engaged during grooming behavior. The study shows that neural responses are highly heterogeneous during grooming, but ensembles were detected in which units were more correlated during grooming than during the entire session. This study presents an important contribution to the field by shedding light on how ensembles of neurons encode innate behavior. The results are convincing.

eLife assessment

This important study uses an innovative genome-wide approach and targeted testing to identify S. aureus genes that affect susceptibility to serum, serum-derived antimicrobial products, and commonly used antibiotics. The findings are significant in that they highlight evidence of evolution of virulence determinants in the setting of exposure to host stressors expected to be present during bacteremia and antibiotic therapy. The evidence is solid, but the presentation could be improved by providing details that clarify the methods and highlighting the limited current understanding of the major target, tcaA.

eLife assessment

This contribution provides important insights into the thermodynamic landscape of cation transporters of the Cation Diffusion Facilitator (CDF) superfamily, together with a detailed structural investigation of the role of the three zinc(II) binding sites of YiiP. Despite the relatively low resolution of the cryo-EM structures presented in this work, the combination of structural, functional and modeling techniques yields solid evidence for the proposed model. This work will be of interest to biologists and biophysicists that work with membrane transporters; it is an excellent example of how different techniques can be combined to obtain relevant information on the complex mechanism of action of a transporter.

eLife assessment

This important study combines behavioral and imaging experiments to understand how levels of important brain chemicals shape the processing of information in the brain in children and young adults. The sample size and data quality are outstanding and some of the data are quite convincing. However, the calculation and interpretation of the brain chemical concentration measurements as well as the interpretation of the model-based behavioral parameters are not fully justified and support for the overall conclusions is incomplete. This work will be of interest to neuroscientists, psychologists, and neuroimaging researchers investigating the developing brain in health and disease.

eLife assessment

This is a valuable addition to the literature as it helps us understand the role of tRNA modifying enzymes in Mycobacterium tuberculosis. By knocking out one of the enzymes, the authors convincingly demonstrate the importance of tRNA-modifying enzymes for intra-host growth of tubercle bacteria. Some of the claims regarding modification as well as the role in virulence could be strengthened through further bioinformatics and phylogenetic analyses as well as experimental approaches. The work will be of interest to microbiologists.

eLife assessment

Müller glial cells of the zebrafish retina can differentiate into all neural cell classes following injury, providing full regenerative capabilities of the zebrafish retina. This study presents a valuable description of transcriptional changes of Müller glia cells in the adult and regenerating retina using single-cell RNA sequencing. The overall evidence supporting the main claims of the authors is solid, but some aspects of the analysis are incomplete and would benefit from additional experimental evidence to support the existence of different types of Müller glia and their distribution in the retina.

eLife assessment

This valuable study provides insights into mechanisms of placental aging and its relationship to labor initiation. The authors provide solid evidence and have thoroughly investigated the molecular characteristics of normal placental aging using in vivo and in vitro model systems and human placental tissue analysis to corroborate their findings. This work contributes to existing work in placental aging and preterm birth and will be of interest to reproductive scientists.

eLife assessment:

This valuable study presents convincing evidence that metabolite levels in Escherichia coli bacteria from a long-term evolution experiment have changed in consistent ways, which in turn can be explained by recurrent mutations in regulatory genes that affect enzyme expression levels. The use of high-resolution mass spectrometry measuring bulk metabolite levels, in combination with existing gene expression and DNA sequencing datasets provides valuable information linking changes in an organism's genome, transcriptome, and metabolome. The current version of the paper lacks clarity in parts, most critically in the introduction, and would benefit from some rewriting to improve its structure, precision, and readability.

eLife assessment

This study reports important findings regarding the systemic function of hemocytes controlling whole-body responses to oxidative stress. The evidence in support of the requirement for hemocytes in oxidative stress responses as well as the hemocyte single-nuclei analyses in the presence or absence of oxidative stress are convincing. In contrast, the genetic and physiological analyses that link the non-canonical DDR pathway to upd3/JNK expression and high susceptibility, and the inferences regarding the function of hemocytes in systemic metabolic control are incomplete and would benefit from more rigorous approaches. The work will be of interest to cell and developmental biologists working on animal metabolism, immunity, or stress responses.

eLife assessment

Muroňová et al. provide valuable information about CDCC146 as a centriole and microtubule associated protein essential for sperm flagellar formation and male fertility. Mutations were identified in human patients suffering from MMAF syndrome, but the evidence that these human mutations were causative of the abnormal phenotype is incomplete. To further explore the causality, mouse models are generated and the findings from the mouse study, support that the key roles of CCDC146 for microtubule-based structures throughout sperm development in general but requires statical analysis.