1,057 Matching Annotations
  1. Oct 2021
    1. In many reptiles, including the red-eared slider turtle Trachemys scripta elegans (T. scripta), gonadal sex is determined by the environmental temperature experienced during embryogenesis

      The genome encodes sex in many vertebrates, including humans (e.g. XX chromosomes lead to female development and XY leads male development).

      But for some organisms, the ambient environment determines sex. In most reptiles, as well as some amphibians and fish, the incubation temperature of eggs directly determines whether males or females will hatch.

      Here is a diagram describing the developmental trajectory of temperature-dependent sex determination in T. scripta: https://ars.els-cdn.com/content/image/1-s2.0-S0303720711006083-gr1_lrg.jpg

    2. gonads of the American alligator (Alligator mississippiensis) also identified rapid changes in Kdm6b expression after shifting eggs from female-producing temperature to male-producing temperature

      A previous study identified temperature-specific Kdm6b expression changes in American alligator during gonad development.

      This data supports the role of KDM6B in temperature-dependent sex determination across reptiles.

    3. Of the six earliest male-biased genes previously reported

      The authors previously found six genes that were enriched in T.scripta embryos at MPT compared to FPT.

      Here, authors tested if KDM6B might affect the enrichment of these genes at MPT.

    4. a dominant role for KDM6B in catalyzing demethylation of the repressive mark H3K27me3 and activating target genes

      KDM6B has been shown to initiate demethylation at H3K27 in various models and systems. This demethylation is closely associated with activation of genes located near the sites of demethylation.

    5. We previously established a method of introducing short hairpin RNAs (shRNAs) in ovo during early stages of T. scripta embryonic development that results in 30 to 50% viability

      In 2017, authors in this laboratory optimized a technique to inhibit gene expression in T. scripta (turtle) embryos.

      Short hairpin RNAs (shRNAs) target complementary messenger RNA molecules for degradation, which blocks the target RNA from being able to make protein. The authors use a virus, called lentivirus, to carry and integrate RNA into the cells. This introduces the shRNA into the embryo while it is still in the egg (in ovo).

    6. We previously sequenced the T. scripta gonadal transcriptome during developmental stages 15 to 21 at male-producing (26°C) and female-producing (32°C) temperatures and found that Kdm6b was up-regulated at 26°C

      The authors originally sequenced the total RNA in turtle embryos at male- and female-producing temperatures (MPT and FPT) to identify differences in transcripts that may contribute to sex development.

      Kdm6b was one of six transcripts that was consistently higher at MPT compared to FPT. Therefore, the authors decided to disrupt KDM6B in turtle embryos to test if it plays a role in sex development.

    7. KDM6B (also called JMJD3) is a histone demethylase that specifically demethylates H3K27me3 and is involved in transcriptional activation during normal development

      KDM6B (the protein) activates genes critical for early organism development, such as gonad specification and body patterning.

    8. Trimethylation of H3K27 contributes to transcriptional repression in many organisms

      H3K27me3 is a histone mark that recruits repressive factors to that region of DNA, which leads to lower expression of nearby genes.

    9. Recently, epigenetic marks, such as DNA methylation and histone modifications of known regulators of gonadal differentiation, have been shown to differ between temperatures in species with temperature-dependent sex determination

      Methylation, or the addition of methyl groups to cytosines on DNA often leads to silencing of transcription of nearby genes.

      Female-producing temperatures (FPT) specifically lead to removal of methylation and the addition of transcription-associated histone tail marks at the promoter for a gene that is critical to estrogen production during female sex determination. These marks were shown across reptiles, including turtles, alligators, and sea bass.

    10. Sexually dimorphic intron retention of these two genes also was detected in the embryonic transcriptomes of alligators and turtles with temperature-dependent sex determination

      Similar intron retention was found in turtles and alligators, which again points to a role for KDM6B transcription in temperature-dependent sex determination across reptiles.

    11. two members of the jumonji family, Kdm6b and Jarid2, in adult female dragon lizards that experienced in ovo sex reversal driven by high temperatures

      Another study on the Australian central bearded dragon showed that different introns in Kdm6b transcripts at high temperatures was sufficient to reverse the genetic sex determination.

  2. Sep 2021
    1. Therefore, functional characteristics (e.g., beak, seed, and fruit sizes) and species abundance (39) may be more important in the structure of mutualistic networks than species identity, supporting the role of ecological fitting (40)

      This study found that phenotypical traits such as the size of a bird's beak and the fruit's diameter were strong factors that determined the likelihood of successful interactions, along with species abundance.

    2. Consequently, high connectance and nonmodular structures are expected, because both are linked to low specialization [e.g., (14, 23)]

      Dalsgaard and colleagues found that tropical areas have a lot of bird species that are obligate frugivores, meaning that they only eat fruited plants. Because fruit is their sole diet, these birds interact with a large variety of plants to ensure that they're consuming enough food to live.

      This type of behavior is commonly associated with a low specialized network because the birds are not displaying any preference toward any particular plant(s).

    3. We assessed species interaction patterns via complex network analyses and used four complementary metrics known to vary geographically and reflect community-level responses to major drivers of biodiversity patterns, such as productivity, climatic seasonality, and historical climatic stability [e.g., (14–16)]

      Differences in geography affects the interaction patterns developed between species. Climate change, differences in species richness, and human impact were shown to dictate the types of networks that dominated those areas.

    4. Previous studies have focused on native-dominated communities in which few or no invasive species occur and mutualistic partners have interacted for prolonged periods of time, developing complex and often coevolved interactions (8, 9).

      Bascompte, Jordano, and Olsen investigated coevolutionary interactions across a wide range of locations, measuring the levels of dependence between various species of plants and animals. They showed that most of these interactions are asymmetric, meaning that one species depends more heavily on the relationship than the other. This asymmetry supports high biodiversity and coexistence of multiple species in an ecosystem.

    5. Oʻahu, in particular, is among the areas most affected by extinctions and biological invasions in the world (12)

      In a 2010 Hawaii statewide assessment of forest conditions and trends, a map illustrated that major vegetation types for multiple islands, especially O'ahu, experienced severe changes in comparison to before the arrival of humans.

    6. Most native Hawaiian forest plants are bird-dispersed, yet no native dispersers remain in most ecosystems (10, 11). Thus, seed dispersal is almost entirely dependent on a handful of introduced vertebrate dispersers, nearly all of which are birds (10, 11).

      The introduction of novel seed dispersers (aka birds) is an important factor regarding in the survival of native Hawaiian plant species. One study showed that the distribution of seeds from native plants is becoming increasingly dependent on not native but foreign birds. C. Chimera and D. Drake also found that these introduced birds tended to spread more seeds from non-native plants rather than native plants.

    7. Mutualistic plant-animal networks are particularly susceptible to species loss (5) and invasions (4, 6, 7)

      A mutualistic network is a web of beneficial partnerships between organisms. Disturbances to that relationship, like from one of the organisms becoming extinct, or by the intrusion of another species, can be harmful for the original partners of that relationship.

    8. As a result, “novel communities” have emerged, characterized by a reshuffling of species, changes in species interactions, and, in some cases, alteration or disruption of ecosystem services maintained by these interactions (3, 4)

      Brodie et al. reviews the concept of secondary extinction, the idea that the extinction of a species, caused by human activity, can lead to the loss of additional species.

      Below is a diagram from the review depicting different types of secondary extinctions. Co-extinction is when the direct impact of humans (red arrow) leads to the loss of one species, causing the loss of another species, which can then cascade into a series of extinctions. Human activity (yellow arrows) also affects interactions between species (gray arrows).

    1. are slowly declining (2, 28)

      To understand the impact of human-made substances on the ozone hole, researchers have been tracking the level of ozone depleting substances in the atmosphere.

      Due to the Montreal Protocol, these substances have been declining.

      Thus, researchers are investigating whether the ozone layer has began to heal as a result of this decline.

    2. The model’s ability to accurately represent polar ozone chemistry has recently been documented (23, 24)

      In order to verify the model, Solomon et al. in Reference 24 compared the model's predictions to actual ozone abundance measurements.

      After accounting for temperature variations and the particles released from volcanic eruptions, the model was in good agreement with actual measurements.

    3. Volcanically driven increases in Antarctic ozone depletion were documented in the early 1990s after the 1991 eruption of Mount Pinatubo and are well simulated by models (15, 16)

      Models have demonstrated that aerosol particles released from volcanic eruptions can deplete the ozone layer.

      Specifically, this modeling work demonstrated that the unusually large ozone hole in 1992 was caused by the eruption of Mount Pinatubo in 1991.

    4. nduce variability from one year to another and could influence trends (2, 13, 14)

      Human-made chemicals are primarily responsible for the formation of the hole in the ozone layer. However, other factors such as variations in weather conditions can produce variations in the size of the ozone hole from one year to the next.

      Researchers in the field have worked to separate the human-made variations from those caused by other factors such as weather.

    5. chlorine and bromine chemistry linked to anthropogenic halocarbon emissions (2, 12)

      It has been well established that human-made chemicals are the primary cause of the hole in the ozone layer. These chemicals are called ozone depleting substances.

      In reference 12, Solomon details the chemical process of ozone depletion in the atmosphere.

    6. the Antarctic ozone hole reached a record size

      Ozone depleting substances (ODS) had already been declining for many years prior to 2015. Thus, it is noteworthy that the hole in the Antarctic ozone layer would reach record size in 2015.

      Why such a large hole was observed in 2015 when ODS have been on the decline is one of the key questions investigated in the current paper.

    7. had not been established by previous studies of the polar regions (2)

      The WHO/UNEP scientific assessment reviews ozone hole data from numerous scientific studies.

      While the 2015 assessment did not report healing in the polar regions, it did conclude that ozone levels had increased in other regions of the Earth since the year 2000.

    8. Ozone recovery involves multiple stages, starting with (i) a reduced rate of decline, followed by (ii) a leveling off of the depletion and (iii) an identifiable ozone increase that can be linked to halocarbon reductions (2, 3)

      Hofmann et al. in Reference 3 used 10 years (1986 - 1996) of Antarctic ozone level measurements to show how ozone recovery occurs over time.

      They show that before an increase in ozone levels occurs, the rate of ozone loss slows down over time.

      They predicted that conclusive signs of Antarctic ozone layer healing could be detected as early as 2008.

    9. both hemispheres (2)

      While the current publication focuses on ozone depletion in the Antarctic, WMO/UNEP periodically reports the state of the ozone layers in the Arctic and in the Antarctic. The reports also provide updates on the levels of ozone depleting substances over time.

    10. attention by scientists, policy-makers, and the public for three decades (1)

      Farman et al. were the first to publish the observation that a hole was forming in the Antarctic ozone layer, and they proposed that chemicals played a key role.

  3. Aug 2021
    1. Z. J. Wang, N. E. Peck, H. Renata, F. H. Arnold, Chem. Sci. 5, 598–601 (2014).

      Professor Arnold's team demonstrates the first enzyme catalyzed carbenoid insertion into N-H bonds. The reaction proceeds in water with moderate yield.

    2. P. S. Coelho, E. M. Brustad, A. Kannan, F. H. Arnold, Science

      This paper shows how directed evolution can be used to modify existing enzymes to carry out synthetically useful reactions. P450 BM3 enzymes were engineered to catalyze cyclopropanation of styrenes with very high diastereoselectivity and enantioselectivity.

    1. coronavirus transmission patterns and the impact of interventions are still poorly understood

      By reviewing the most updated understanding of COVID-19 at the time, the authors identified a research gap concerned with the transmission patterns with and without interventions taken.

      A better understanding of this aspect is necessary for evaluating the effectiveness of public health measures.

    2. (10–15)

      Three of these studies investigating the spreading patterns agree that human mobility is a critical factor in determining the spreading pattern of these infectious diseases, e.g., malaria, H5N1 influenza, etc.

    3. (7, 8)

      These two articles summarized the measures introduced in the early stage of the outbreak.

      Kraemer and the team showed that the mass control over transportation effectively restricted the spread of COVID-19.

    4. (3, 4)

      Based on the RNA sequencing results, both works suggested that the novel coronavirus is closely related to a previously identified bat virus.

    5. (1, 2)

      The two studies presented images and genome sequencing results of the novel coronavirus. The results agree on the identification of a new type of human-infecting betacoronavirus.

    1. genetic material of parvovirus B19 was also detected in early Neolithic skeletal remains, despite the relatively unstable nature of its single-stranded DNA genome

      One of the reasons that DNA is typically easier to recover from ancient samples is that it is usually found as 2 strands twisted together making it more stable. Parvovirus B19 (B19V) has a genome that is a single strand instead of a double, meaning it typically would not last as long in remains. These authors recovered B19V DNA from remains that were between 0.5 and 6.9 thousand years old and demonstrated the virus has been associated with humans for thousands of years.

    2. Most studies on ancient viruses have thus far focused on viruses with a double-stranded DNA genome

      DNA from variola virus which causes smallpox has been recovered from a 300 year old Siberian mummy and a Lithuanian mummy from the 1600's.

      DNA from hepatitis B virus has been recovered from skeletons found in Germany, a 16th century child mummy in Italy, and skeletons scanning a period of nearly 4,000 years from a variety of regions.

    3. favorable circumstances, including natural mummification or preservation in cold environments

      Some environments are more likely to preserve genetic material than others. The oldest DNA samples have been recovered from permafrost or regions where the ground remains permanently frozen. Other favorable environments include high salt concentrations, very dry environments like deserts, or environments with very low oxygen like bogs a type of wetland that contains large amounts of dead plant material.

    4. RNA was extracted from the remains of a 14,300-year-old Pleistocene canid preserved in permafrost

      Authors generated RNA data from wolf skins and liver tissue of an ancient wolf relative. This is the oldest RNA ever sequenced and the RNA was also tissue specific. This work demonstrates that RNA could possibly be recovered from tissues preserved over thousands of years.

    5. although the directionality of this cross-species transmission event has never been formally established (supplementary text S1)

      In the supplement, the authors use previous studies to assert that while not formally established, the transmission of RPV spilling over into humans is much more likely than the opposite occurrence. They support this with 4 points.

      1. Cattle and other hoofed animal populations were likely large enough to support RPV before human populations were large enough to support measles.
      2. Older descriptions of RPV seem to exist than descriptions of measles.
      3. Other viruses related to measles infect cattle, so it is more likely that RPV infected humans and became measles once rather than measles becoming a cattle virus several times.
      4. Other Paramyxoviruses originated in domesticated animals and jumped to humans. Even with this evidence it cannot be ruled out that transmission from humans to cattle occurred.
    6. with the most reliable (and oldest) estimate falling at the end of the ninth century CE {mean, 899 CE [95% highest posterior density (HPD) interval, 597 to 1144 CE]}

      Wertheim and Pond demonstrate the purifying selection or the removal of damaging alleles can make pathogens seem younger than they really are. Using models that take this phenomenon into account, they provide evidence that the origin of measles is older than previous estimates showed.

    7. Roman sources from the fifth century BCE on

      This book describes the history of outbreaks of disease from cattle in humans from the Roman empire to the 20th century.

    8. numerous concurrent human-bovine epidemics in the early medieval period (here, 6th to 10th centuries CE) were caused by an immediate ancestor of MeV and RPV that was pathogenic to both cattle and humans

      Measles is only able to infect humans, while rinderpest virus is only able to infect cattle. This article provides evidence that outbreaks that occurred during the medieval period were a separate but related virus that was able to infect both cattle and people.

    9. there is broad agreement that a number of settlements in North Africa, India, China, Europe, and the Near East began to surpass the CCS for MeV by around 300 BCE, presumably for the first time in human history

      This study assessed regions where major settlements increased in size (upswept) or declined significantly and stayed down without rebounding (downswept). They identified 18 total significant upsweeps including those around 300 BCE.

    10. epidemiologists have held that given the speed with which measles epidemics occur and the efficacy of acquired immunity, MeV could not have become endemic in urban populations below the CCS

      This book provides information on measles expansion, consolidation, and retreat pre and post vaccine introduction within different geographical regions. They present mathematical models to describe the spread of measles epidemics and forecast geographical spread in various conditions.

    11. Populations large enough to support continuous MeV transmission—larger than the MeV critical community size (CCS) of 250,000 to 500,000 individuals

      Critical community size (CCS) is the smallest population size that can support the continued persistence of a human-to-human pathogen that is unable to infect animals. Bartlett estimated the critical community size to be around 250,000 using data from Manchester records. Black then used case reports from 19 island communities to establish a CCS of 500,000. Finally, Keeling and Greenfell used prevaccination data from England and Wales and estimated a CCS between 250,000 and 400,000.

    12. The earliest clear clinical description of measles is often attributed to the Persian physician Rhazes, writing in the 10th century CE

      Rhazes was a notable physician who authored more than 200 books and treatises or formal works on subjects like medicine and philosophy. His document "A Treatise on Smallpox and Measles" was the first book to distinguish between the two diseases.

    13. RNA tends to be much less stable in the environment than DNA, making the recovery of MeV genetic material from archaeological remains unlikely

      RNA degrades more rapidly in the environment because it exists as a single strand while DNA is typically found in a double stranded structure. RNA is also made from ribose while DNA is made with deoxyribose which are two different sugars. The difference in the structure of these sugars makes RNA more susceptible to breaking down when it encounters water.

    14. for example, through the use of ancient viral sequences

      Muhlemann and colleges isolated DNA from ancient human parvovirus 19 and hepatitis B viruses to obtain genomes sequences. These sequences were then used to assess the historical relationship between these viruses and the human population and learn more about viral evolution.

    15. which is referred to as the time-dependent rate phenomenon

      These studies look at how evolutionary rates change over time and how these alterations can be accounted for in models. Ho and colleagues assert that rates of evolution change over time as a result of a variety of factors and refute the claims of Emerson and Hickerson. Aiewsakun and Katzourakis demonstrated that the time dependence in rate estimates applies for viruses. Accounting for rate variation in can provide more biologically realistic models.

    16. It is generally accepted that measles emergence resulted from a spillover from cattle to humans

      Wolfe and colleagues assessed the origin of significant human infectious diseases. They found the origins of diseases varied based on climate and identified stages of a disease transitioning from an animal pathogen to a human pathogen. They found that diseases like measles from mild climates frequently originated from domestic animals like cattle.

  4. Jul 2021
    1. B. D. Levin, K. A. Walsh, K. K. Sullivan, K. L. Bren, S. J. Elliott, Inorg. Chem. 54, 38–46

      The study shows the loss of axial methionine from cyt c. The same phenomenon was observed over a range of cyt orthologs. In Professor Arnold's work, the labile nature of methionine in cyt c is believed to be responsible for the improved efficacy of the C-Si bond forming biocatalyst.

    2. 22

      In this study, Professor Arnold's group used protein-engineered variants of cytochrome P450 BM3 to bring about highly diastereoselective and enantioselective cyclopropanation reaction of styrenes from diazoester. Variant BM3-CIS was identified as a competent cyclopropanation catalyst. It exhibits a strong preference for the cis product and forms both diastereomers over 90% ee and is as stable as the wild-type enzyme. P450 BM3 works on a wide range of substrates with both electron-donating and electron-withdrawing substituents in styrene.

    1. Measles differential diagnosis remained a challenge well into more recent times

      Measles is easily confused with smallpox because they both cause rash and fever. Distinguishing smallpox and measles is no longer a problem since smallpox has been eradicated.

    2. we first heat-treated 200 mg of the formalin-fixed lung tissue to reverse macromolecule cross-links induced by formalin and subsequently performed nucleic acid extraction

      While fixing with formalin preserves biological samples, it causes cross-linking or the chemical joining of molecules. These chemical bonds interfere with the sequencing process. Treating the tissue with heat before purifying the genetic material helps to fix this problem.

  5. Jun 2021
    1. Several studies suggest that the phylogenetic relationships of species contribute to structuring mutualistic networks

      Normally depicted as the "tree of life" (shown below), the phylogenetic tree traces the genetic lineage of organisms over time. Two species share a phylogenetic relationship when they share a common ancestor. An example of a phylogenetic tree can be found at https://www.nationalgeographic.org/media/tree-life/

      The authors of the cited paper found that phylogenetic relationships can influence the type of networks species build and explain the type of species involved in these interactions.

  6. Apr 2021
    1. it has been shown that anti-CTLA-4 interferes with signals that normally down-regulate T cell responses

      Administering anti-CTLA-4 treatment in the absence of a tumor causes T cell responses to slow down. At the time this paper was published, it was not clear why this was the case.

    2. mice deficient in CTLA-4 exhibit severe T cell proliferative disorders

      The absence of CTLA-4 results in out-of-control cell division of T cells. Even though CTLA-4 is an inhibitory receptor, it is needed to produce the right balance of T cell activation, and its complete absence can be dangerous to organisms.

    3. antibody cross-linking of CTLA-4 has been shown to inhibit

      Using antibodies, scientists can induce dimerization of the receptor CTLA-4. Dimerization, a process whereby two similar molecules come together to form a single structure, is often the cause of signaling through a receptor. This experiment shows that the effect of CTLA-4 signaling is inhibition of T cell activation and expansion.

    4. additional costimulatory signals are necessary for T cell activation

      Mueller, Jenkins, and Schwartz summarize the models proposed by several scientists to explain why T cells only respond to foreign invaders and not to peptide-MHC on healthy cells. They summarize it as the "two-signal model of T-cell activation," whereby there must be another signal necessary for T cells to be activated.

  7. Mar 2021
    1. The SOMA’s small form factor prevents obstruction in the lower GI tract and allows for easy ingestion. It is smaller in volume than the U.S. Food and Drug Administration (FDA)–approved daily dosed osmotic-controlled release oral delivery system (OROS) (Ø 9 mm × 15 mm), a nondegradable drug delivery capsule with obstruction rates of 1 in 29 million

      This paper discusses that OROS controlled-release devices showed a low occurance of any significant GI events. When used correctly, extended-release products provide substantial therapeutic and convenience benefits without additional risk. Their small size allows for easy ingestion without significant difficulties

    2. We employed geometric models of tortoise shells as initial guesses for the shape

      Specifically, this paper shows that the exact geometry of highly domed terrestrial species is close to optimal for self-righting, and the shell's shape is the predominant factor of their ability to flip back. This study illustrates how evolution solved a far-from-trivial geometrical problem

    3. Preclinical technologies for gastrointestinal (GI)–based biomacromolecule delivery, including permeation enhancers, nanoparticles, and mucus-adhering devices, enhance uptake but can generally only safely achieve bioavailabilities on the order of 1%

      The conclusion from these sources is that most of the technologies in clinical trials are small scale and not groundbreaking. Even the more clinically advanced oral drugs examples of oral bioavailability appear to produce oral bioavailability values of only 1–2% and are, therefore, only currently suitable for a limited range of drugs.

    4. Although the idea of delivering biologic drugs to the GI tract via injection has been previously hypothesized and tested via endoscopic procedures

      demonstrated proof‐of‐concept experiments in swine that microneedle‐based delivery has the capacity for improved bioavailability of a biologically active macromolecule. Moreover, the paper shows that microneedle‐containing devices can be passed and excreted from the GI tract safely. These findings strongly support the success of implementation of microneedle technology for use in the GI tract.

    5. Routine procedures in which gastroenterologists use 5-mm 25-gauge Carr-Locke needles for GI injection provide strong clinical evidence for this action’s safety

      No perforations (injuries) caused by the examination during 1210 upper endoscopies that were performed as part of this trial conducted by gastroenterologists (doctors that study the GI tract) Carr-Locke needle: https://www.steris.com/-/media/us-endoscopy-images/endoscope-devices/carr-locke_injection_needle_300.ashx

    6. Additionally, gastric tissue regenerates quickly, and the fluidity of the mucous barrier seals temporary defects in the lining

      The gastrointestinal lining produces a wide variety of peptides which may contribute to protection from injury as well as repair after injury occurs. Restitution, the initial phase of mucosal repair, is accomplished by rapid moving of the epithelium to reestablish surface epithelial continuity (i.e. seal any injuries)

    7. Orally bioavailable biologic dosage forms may allow health care providers to prescribe these effective medications more quickly, yet the development of such systems poses challenges

      This study shows that orally administered devices could enable the systemic uptake of drugs by engineering around the physiological barriers present in the gastrointestinal (GI) tract. These designs must significantly increase drug bioavailability, deliver a correct dose and remain safe when taken frequently. This paper discusses how these physical methods stand to provide a solid set of alternatives to the classic hypodermic needle administration of drugs.

    8. Motivated by patient and health care professional preference for oral delivery, research on ingestible biomacromolecule formulations began in 1922, the same year as the first insulin injection

      When surveyed, 208 women who were more than 2 years post-breast cancer diagnosis were surveyed about their preferences for daily oral tablets or monthly intramuscular injections. Sixty-three percent of these women preferred oral tablets. This preference has not changed overtime. In 1923, there was an experiment to see if insulin could be delivered orally via an alcoholic solution. It was found that a dose of insulin by mouth required double the dose of insulin administered through injection. That meant it would be much more expensive than the existing method. The oral dose was also much harder to control and unpredictable. Overall, it was determined that alcohol was not a sufficient medium to provide an oral dose of insulin.

    9. The discovery and purification of insulin transformed our capacity to effectively treat diabetes mellitus (3)

      This study showed that purification, or removal of other chemicals in the insulin solution, and treatment of insulin dependent diabetes mellitus (IDDM), or a disease often called sugar diabetes because the condition makes it difficult to convert food to energy. This leads to high sugar levels in the blood with intensive treatment (either multiple insulin injections per day or an external insulin pump) delayed the onset and slowed the progression of diabetic retinopathy (a disease of the eye caused by diabetes) when compared to conventional therapy.

    10. Orally administered therapeutic proteins

      Drugs that are orally administered must have various coatings to avoid being broken down within the gut. Although this does pose challenges, it is still promising to study and eventually utalize orally administered drugs for local GI targets.

  8. Feb 2021
    1. The size and material makeup of the SOMAs are similar to those of FDA-approved ingestible devices such as OROS capsules, ingestible temperature sensors, and capsule endoscopy systems, supporting likely comparable environmental assessments (24, 30, 31).

      The OROS osmotic (OSM) dosage form optimizes extended-release drug administration by controlling the rate of drug release for a predetermined time. OSM products include prescription medications for urology, Central Nervous System, and cardiovascular indications, as well as over-the-counter nasal/sinus congestion medications. This shows that the SOMA device is similar to previous devices, meaning it is a less risky device, because other products have been approved with similar materials.

    2. health care providers delay insulin initiation an average of 7.7 years and instead prescribe less effective oral medications

      This study evaluated the management of people with type 2 diabetes prescribed two or more oral medications, and/or insulin. It was seen that on average, the median time to insulin for patients prescribed multiple oral agents was 7.7 years. This showed that many people with type 2 diabetes received inadequate monitoring and had poor blood sugar control during the beginning of their treatments.

    1. soft robotic quadrupedal “walker”

      A soft robotic quadrupedal is a type of soft robot that has four appendages. These appendages can be contracted using a pneumatic network to allow for maneuverability.

    2. Thermoelectrics can change the IR signature, and electronic displays can change the visible color, but neither technology has control over both IR and visible coloration

      Thermoelectrics convert heat into electrical energy. Electrical energy can be measured. Researchers can then use this information to decided how to change the IR signature. Electronic displays are devices that display images for visualization electronically, like a television. Each of these technologies, thermoelectrics and electronic displays, work independently. Electronic displays have no control over temperature. Meanwhile, thermoelectrics cannot display images.

      Here, the author is demonstrating the novelty of his work. Rather than integrating both thermoelectrics and electronic displays onto the robot, a liquid network can do the work of each technology, greatly simplifying the soft robotic design.

      The liquids used in the microfluidic channels of the device can be colored and heated (or cooled). Therefore, both temperature and color can be controlled simultaneously using one methodology.

    3. mechanical actuation results from pneumatic pressurization and inflation of an independent network of microchannels (pneu-nets) embedded in highly extensible elastomers (6, 7)

      Pneumatic networks, also known as PneuNets, are commonly used in soft robotics to illicit movement. Pneumatic simply means to operate by air or gas under pressure. PneuNets are networks of small channels embedded into soft robots that can be inflated or deflated with pressurized air to allow for maneuverability.

      Here, researchers created two independent sets of microchannels inside of the robot. One set is filled with air and functions as the PneuNet, allowing the robot to move. The other set is filled with liquid and changes the color or temperature of the device; this set does not facilitate movement.

      This link provides videos that demonstrate how a PneuNet functions: https://softroboticstoolkit.com/book/pneunets-bending-actuator

  9. Jul 2020
    1. HMGA2 has been associated with variation in height, craniofacial distances, and primary tooth eruption in humans (18, 19)

      Fatemifar et al. (2013) showed that HMGA2 is associated with craniofacial features, such as the width of the eye region, the width of the lower part of the nose, and the height of the mid-brow prominence.

      Ligon et al. (2005) had previously reported an 8-year-old boy with a shortened HMGA2 gene that exhibited widely-spaced eyes, a large head circumference, and premature dentition.

    2. exhibits severe growth retardation (17)

      Zhou (1995) found that, in mice, mutant alleles sometimes arise from deleted DNA or from chromosomal inversions. When these mutations cause the protein Hmgi-c to inactivate and not be expressed in mice, the result is dwarfism. This protein is associated with the HMGA2 gene.

    3. This tree was almost identical to our previous tree (15).

      The previous tree from Lamichhaney and colleagues in 2015 showed that the initial split between warbler finches and other finches happened 900,000 years ago. Rapid divergence of ground and tree finches occurred 100,000 — 300,000 years ago.

      Hybridization in finches has influenced the evolution of beak shape. Using phylogenetic studies along with genomic data allowed researchers to reveal some of the genetic variation that underlies finch beak diversity.

    4. only one regulatory gene, ALX1, is known and it regulates variation in beak shape (15), which was not associated with survival in 2004–2005.

      Lamichhaney et al. (2015) previously scanned the genomes of finch populations that were related but displayed different beak structures. They found that the ALX1 gene was a strong candidate for regulating the variation in beak morphology. ALX1 encodes a protein that is vital in developing structures from embryonic tissue that will form craniofacial structures.

    5. Thus, body size was possibly subject to selection, but beak size was a more important factor affecting the probability of survival independent of body size (11, 12). However, the genetic basis of the selected traits remains unknown.

      Grant and Grant (1994) explored hybridization among finch species over 17 years. They concluded that hybrid traits were morphologically intermediate, which indicated the parent genes contributed to the offspring phenotype equally. Hybrids also varied more phenotypically.

      Even though both were heritable, beak size seemed to be more important that body size because the beak's relationship to food acquisition.

    6. Beak sizes diverged as a result of a selective disadvantage to medium ground finches with large beaks when food availability declined through competition with large ground finches during a severe drought in 2004–2005 (11).

      Grant and Grant (2006) reported that the finch species Geospiza fortis diverged in beak size from one of its competitors, G. magnirostris. This divergence happened on an isolated Galapagos island 22 years after G. magnirostris arrived to share a habitat with G. fortis.

    7. Furthermore, although some signaling molecules affecting beak dimensions in Darwin’s finches have been identified (14)

      Abzhanov and colleagues (2004) analyzed various growth factors that were known to be expressed during craniofacial development of birds. When looking at Darwin's finch species, some factors showed no correlation whereas other factors showed a correlation with beak size, but not beak shape. However, researchers did find that the expression of the Bmp4 molecule had strong association with both beak size and shape.

    1. With respect to putative downstream effectors, planarians can regenerate double heads after pharmacological gap junction inhibition, and β-catenin is implicated in gap junction formation and function (19–21).

      Nogi and colleagues identified the role of gap junctions, which allow ions or other small molecules to move between cells, at the planarian amputation sites.

      Shaw and colleagues determined the role of microtubules in the formation of gap junctions. The ability of cells to stick together (cell adhesion) is crucial to this formation.

      Guger and colleagues identified that β-catenin may play a role in communication between cells via gap junctions.

    2. More than 100 years ago, T. H. Morgan reported that fragments with closely spaced anterior and posterior amputation planes occasionally regenerate two-headed animals (22, 23)

      This early (1800s) research on planarians provides an essential background for the regenerative capabilities of planaria. The observations from this research is essential for understanding planaria today.

    3. “something in the piece itself determines that a head shall develop at the anterior cut surface and a tail at the posterior cut surface”

      Here, Morgan suggests that regeneration of a head versus a tail is related to the location of the amputation and the cells that reside there.

    4. Indeed, β-catenin regulation can be Wnt-independent in vertebrate cells, and Dishevelled remains the most upstream known β-catenin regulator during early sea urchin development (14, 17, 18)

      This research shows that β-catenin plays a role in all animal species studied including vertebrates and invertebrates, but how it is regulated in vertebrate animals may be different than in invertebrates. This is important to understanding stem cell regulation because it appears to regulated differently in planaria (invertebrate) than in humans (vertebrate).

    1. this would be consistent with recent findings (33) indicating that a glial-derived factor (adenosine) accumulates during DBS and plays a role in DBS-mediated attenuation of thalamic tremor.

      In 2008, Bekar et al. demonstrated that the adenosine triphosphate (ATP) byproduct, adenosine, accumulated following deep brain stimulation. Adenosine would then activate adenosine A1 receptors which in turn depressed excitatory transmission in the thalamus and reduced tremors.

    2. We have developed and employed optogenetics technology

      One of the paper authors, Karl Diesseroth, is attributed with implementing light-sensitive proteins called opsins in neurons to control their activity. He coined the term "optogenetics" to signify that neurons can be selectively targeted using genetics which in turn encodes proteins that are optically controlled.

    3. light-power density sufficient to drive physiologically significant microbial opsin currents

      Adamantidis et al. previously showed that a light power intensity of 1mW/mm2 was necessary to drive the action of microbial opsin currents in hypocretin-producing neurons within the lateral hypothalamus .

    1. [8 ± 1 R/Ra (SD)]

      In this expression, R stands for <sup>3</sup>He/<sup>4</sup>He in an igneous rock sample. Ra symbolizes the same ratio expressed relative to the values obtained in air. Thus, in this case, the value of R/Ra in MORBs is 8, and this value is within 1 standard deviation (SD) of the mean R/Ra.

    1. this benefit persisted in a 2-year follow-up study (31)

      An initial values affirmation intervention can have long-lasting positive effects.

      In one study, a group of students received a values affirmation intervention at the start of 7th grade (initial findings reported in reference 23), and their academic performance was monitored through 7th and 8th grade. African American students that received the intervention had larger and more persistent increases in grade point average than those who did not receive the intervention. This suggests that a single intervention could have long lasting positive effects.

    2. 23

      Cohen and colleagues tested whether a simple intervention could reduce the effects of stereotype threat for African American students.

      They found that having students complete a short writing exercise, in which they wrote about a value they found important (values affirmation), reduced the gap in performance between African American students and other students.

      The full PDF download of this paper is available in the Related content tab.

    3. women’s performance on difficult math and science tests can suffer insofar as they worry that their poor performance could be seen to confirm a negative gender stereotype (18

      Spencer, Steele, and Quinn performed several experiments to determine whether the stereotype that men are better at math than women affected women's performance on math tests.

      They found that when the gender stereotype was reinforced before a hard math test women performed even worse compared to men on the test than usual. However, describing the test as not producing gender differences eliminated the difference in performance between men and women.

  10. Jun 2020
    1. During embryonic development of both vertebrates and invertebrates, β-catenin regulates a variety of cellular processes, including organizer formation, cell fate specification, proliferation, and differentiation (1–9)

      Schneider and colleagues identified that β-catenin regulates dorsal-ventral polarity in vertebrates (animals with backbones).<br> Later research identified that β-catenin is modulated by the Wnt signaling pathway. It plays a role in forming groups of embryonic cells that direct the initial formation of the neural plate (basis for the nervous system) and the complete body axis (head vs feet ends of an organism) of the animal.

    2. In adult animals, the Wnt/β-catenin pathway participates in regeneration and tissue homeostasis; misregulation of this pathway can lead to degenerative diseases and cancer in humans (9–12)

      Several studies identified the role of β-catenin in regeneration of tissues and its potential relationship to degenerative diseases and cancer, which are both related to regulation of cell division. Identification of active β-catenin in adult tissue is important for potential treatment of these disease.

      Watch this video to find out more about the relationship between cell division and cancer: https://www.hhmi.org/biointeractive/eukaryotic-cell-cycle-and-cancer

    3. In response to upstream cues, such as Wnt ligands binding to Frizzled receptors, β-catenin accumulates in nuclei (Fig. 1A) and invokes transcriptional responses that direct the specification and patterning of tissues (13, 14)

      Stadeli and colleagues research indicates that β-catenin plays a major role in regulating the body pattern and head/tail orientation of cells during development.

    4. Hence, loss of APC leads to a rise in β-catenin levels that is sufficient to drive transcriptional responses (15)

      This early research provides evidence for the importance of chemical signaling pathways as the major form of cell-to-cell communication and play a role in the body throughout an animal's lifetime.

    5. Dishevelled has multiple functions but plays an essential role as a positive regulator of β-catenin by inhibiting the destruction complex (16)

      Wallingford and colleagues found evidence for the important role that the protein known as Dishevelled plays in cell fate (how cells know what type of cell to become); how cells know where to go (head or tail), and how cells interact with each other in the animal body. Dishevelled has been found to play this same role across many animal species, which indicates its importance.

    1. Thus far, the most fossiliferous sections from this time interval occur in the Williston, San Juan, Hanna, and Denver basins along the eastern margin of the Rocky Mountains in North America

      Basins located in the eastern Rocky Mountains of the United States were the primary area of interest. Maps showing the location of several of these basins can be seen at the following sites: Map of Williston Basin https://serc..edu/details/images/35362.html

      Map of San Juan Basin https://www.mapsofthepast.com/san-juan-basin-usgs-1959-2941-x-23.html

      Map of Hanna Basin https://www.researchgate.net/figure/Map-showing-the-Hanna-Laramie-and-Shirley-Basins-Wyoming-including-major-structural_fig1_284185996

      Map of the Denver Basin https://www.researchgate.net/figure/Map-of-the-Denver-Basin-within-Colorado-Wyoming-and-Nebraska-with-structure-contours-on_fig1_265508368

    2. Corral Bluffs study area, a single continuous (physically traceable) (~27 km2) outcrop from the Denver Basin that preserves the biotic recovery of a terrestrial ecosystem in the first million years post-KPgE

      Earlier research showed that the Corral Bluffs area has a relatively continuous K–Pg boundary stratigraphic sequence. It is the most extensive surface exposure in the Denver Basin and allows for the opportunity to interpret fossil collections in the context of K–Pg boundary extinction and recovery.

    3. re we observe a 5.1 °C warming event (17.5 ± 3.4 °C 1SE to 22.6 ± 3.5 °C 1SE) occurred from the K–Pg boundary through the first ~60 ka of the Paleocene, similar to the ~5 °C in ~100 ka warming pulse inferred from δ18O of phosphatic fish scales from the El Kef K–Pg section of Tunisia

      In their study, MacLeod et al. reported the values of the oxygen-18 isotope (δ18O) in phosphate compounds isolated from sand-sized (~0.1 to 2 mm) remains of fish teeth, scales, and bone from El Kef, Tunisia, that indicate a warming trend of ~5°C beginning at the K-Pg boundary and lasting for ~100,000 years. This supported similar findings by the author of this research article.

    4. from the Williston Basin,

      Tobin et al. analyzed fossil bivalve shells for carbonate-clumped isotopes. Their findings confirmed a decrease in summer temperatures over the last k.y. of the Cretaceous. This cooling trend accounts for declines in vertebrate and invertebrate biodiversity, making the destabilized ecosystem more susceptible to the asteroid impact.

    5. Following the KPgE, many angiosperm clades diversified (4). The Corral Bluffs section preserves the oldest known occurrence of the Leguminosae, or bean family, as evidenced by fossil seedpods and leaflets dated to 65.35 Ma

      In communities of present-day mammals, ecological richness is primarily driven by vegetation type. The fossil record shows that some plant groups, such as gymnosperms (pines, spruce, and firs), decreased in diversity as a result of the K-Pg extinction. Angiosperms (flowering plants), on the other hand, underwent a rapid increase in diversity. When becoming dominant, angiosperms allowed for the evolution of a diversity of mammals and other animals.

    6. Finally, the Denver Basin has well-documented Cretaceous and Paleocene strata, a precisely dated K–Pg boundary, and abundant, geographically dispersed plant fossils, but, prior to this study, a sparse and fragmentary vertebrate fossil record

      Several different dating techniques have determined that the K–Pg boundary layer in the Denver Basin overlaps with the age of the K–Pg boundary layer in the Hell Creek Formation in Montana. The age of both these areas is the same as that of tektites from Chicxulub where the asteroid impact occurred. This provides strong support for the contemporaneous deposition of ash and debris across western North America directly after the Chicxulub impact.

    7. Fossils of terrestrial and freshwater organisms from the first million years after the KPgE are exceedingly rare worldwide,

      The authors spent many years looking for mammal fossils in different locations in the western U.S.

    8. These concurrent plant and mammal originations and body mass shifts coincide with warming intervals, suggesting climate influenced post-KPgE biotic recovery.

      It has been shown that there is a strong relationship between Earth’s geochemical cycles and the biosphere. An example would be that the many volcanic eruptions occurring in the Deccan Traps likely released greenhouse gases that triggered post-KPgE warming periods. These periods resulted in a greater diversity of plant species, which in turn supported larger bodied mammals.

  11. Apr 2020
    1. HMGA2 and ALX1, two closely linked loci (7 Mb apart) previously shown to be associated with variation in bill morphology in Darwin’s finches (15, 26)

      Lamichhaney and colleagues (2015) searched genomes of closely related species that had different beak sizes and identified ALX1, a homeobox gene that controls development in the face and neck, and correlates well with differences in beak shape.

      Lamichhaney and colleagues (2016) analyzed finches whose beak sizes changed during a drought and identified HMGA2, a nearby gene locus also related to beak size.

    2. surrogate experiment, for example with finch models and/or playback of tape-recorded song (27)

      Grant et al. did the experiment described here with a population of G. difficilis on Isla Genovesa.

      They played tape-recorded songs from several G. difficilis populations (Isla Genovesa, Isla Wolf, and Isla Darwin) and demonstrated that the finches responded strongly to their own population's song, weakly to the Isla Darwin population's song, and not at all to the Isla Wolf population's song.

    3. the chance occurrence of strong selection against large bill size in a competitor species, G. fortis, in 2004-05 (12, 26)

      In 2004-05, a severe drought caused competition between two species of finch on the island of Daphne Major. The medium ground finch (G. fortis) and large ground finch were in competition for decreased food sources. Because medium ground finches with large beaks were at a disadvantage, the size of beaks for these finches decreased as a result of this selection pressure.

      This natural experiment was studied by Lamichhaney and colleagues (2016) and by Grant and colleagues (2014).

    4. in laboratory populations of animals (21)

      Bolsted and colleagues describe how they changed the allometric relationship of wing size to body size in fruit flies, Drosophila melanogaster, through artificial selection.

      This shows that selection can change allometric relationships and supports the authors' suggestion that natural selection is the cause of the changes in allometric relationship between bill size and body size in the Big Bird population.

    5. The ability of finches to efficiently exploit the large woody fruits of Tribulus cistoides in dry seasons, and particularly during droughts and limited food supply, is a function of bill size, especially bill depth (12)

      By measuring bill size and recording bird mortality on Daphne Major during a drought that occurred in 2004-05, scientists were able to establish the characteristics of bills that were adaptive during this period of decreased food supply.

      The plant species mentioned is a food supply for the Big Bird lineage, so this data on bill morphology is relevant to understanding this hybrid population.

    6. due to large bill and body size, and a distinctive song (12)

      In "40 Years of Evolution" (reference 12), Grant and Grant devote an entire chapter to the analysis of this possible new hybrid species that supports these conclusions about bill and body size, as well as song. 

      Their analysis includes extensive pedigrees and data on beak depth and width, heterozygosity, and song analysis.

      The current paper explores the beak morphology and genetic data more closely to contribute to the understanding of the hybrid lineage success and reproductive isolation.

    7. until recently

      In 2010, Grant and Grant analyzed genetic data to search for the effect of breeding with immigrant birds (reference 16). They used genetic studies to quantify the effect of genes from the same species (from populations on other islands) compared to those of different species.

    8. finch species imprint on features of their parents early in life

      Rosemary and Peter Grant developed this idea based on observations of mating pairs, as well as experiments. In some experiments, they played recorded birdsongs from either the same or a different species and recorded the birds' responses. Other experiments involved presenting birds with a stuffed specimen of either the same or a different species and recording their responses.

    9. An immature male finch immigrated to the small Galápagos Island of Daphne Major (0.34 km2) in 1981 (11–13).

      Rosemary and Peter Grant have led the study of the bird species of the Galapagos Islands since the 1970s. Individual birds on the island have been banded and described, so migrants such as the one described can be identified when they arrive.

    10. stringent criteria

      Schumer and colleagues present three criteria: 1) demonstration of a mechanism of reproductive isolation, 2) evidence of hybridization (preferably genetic and based on whole genome evidence), and 3) hybridization-derived isolation (establishing that the hybridization led to the reproductive isolation and not some other factor).

    1. Researchers have used approaches including chemically modifying collagen into an ultraviolet (UV)–cross-linkable form

      Researchers at Rutgers created a scaffold, or 3D pattern of cells, by assembling Type-1 collagen. collagen is the most abundant tissue in the ECM. Type-1 collagen specifically is the most abundant collagen used to strengthen and support tissues in the body. The researchers chemically modified the collagen such that it can assemble into 3D structures in the presence of ulraviolet light (light with a shorter wavelength than visible light but linger than x-rays and gamma rays). This allowed researchers to control 3D assembly of collagen through light. Similarly, collagen structures can be assembled by controlling pH, temperature and collagen concentration using chemically modified collagen.

    2. (23)

      Jordan S. Miller notes that 3D printing facilitated creation of tissue constructs with live cells. However, he argues that in order to engineer functional artificial organs, the construct should contain 1–10 billion functioning cells. Furthermore, these constructs should control the spatial arrangement of cells and contain complex vascular networks and functional nerves.

    1. Linear actuation can be achieved with planar HASEL actuators by implementing a fixed prestretch in one planar direction and applying a load in the perpendicular planar direction (29).

      Previous work done by S. J. A. Koh et al. tested how to achieve linear actuation with planar actuators using this method, allowing these authors to replicate these trials using their single and two-unit actuators.

    2. Dielectric materials made of silicone sponges swollen with silicone oil (18) continued operating after dielectric failure but demonstrated actuation strains only below 5%.

      Experiments have been performed to test the ability of liquid dielectrics versus solid dielectrics. Liquid dielectrics are able to repair themselves after dielectric failure or damage. Using liquid dielectrics allow for longer lasting actuators, resistant to breakdown, puncture and other damage. However, they do not generate too much movement (<5% strain).

    3. Fault-tolerant DE actuators

      Fault tolerant dielectrics are able to recover from breakdown. There are multiple ways to accomplish this recovery. The device in the paper uses a liquid dielectric. When the liquid dielectric breaks down, only a portion of the overall dielectric is effected. Then when the breakdown event stops, the electricity stops, the remaining dielectric liquid fills in the damaged areas, effectively healing the actuator.

    4. However, DE actuators are driven by high electric fields, making them prone to failure from dielectric breakdown and electrical aging (15).

      When voltage is applied across dielectric materials, they do not conduct electricity but rather get polarized, by accumulating positive and negative charges within the material. Dielectric breakdown happens when the voltage is so high that the dielectric begins conducting electricity. A breakdown event briefly makes the dielectric material conductive, allowing for high amounts of current to flow through, typically causing permanent damage to the material

    5. Electrically powered muscle-mimetic actuators, such as dielectric elastomer (DE) actuators, offer high actuation strain (>100%) and potentially high efficiency (80%) and are self-sensing (12–14).

      Experiments have been conducted to optimize the abilities of dielectric elastomers. It has been discovered that pre-straining the elastomers, like stretching a balloon, allows the elastomers to achieve a higher strain at a faster rate. Pre-straining is the process of applying a force to a material before actual use. When you stretch a balloon before blowing air into it, you are "pre-straining" the balloon. This allows the material to "get use to" the forces it will experience. Also, computational models helped determine the best ways to pre-strain elastomers such that a specific 3D shape is achieved.

    6. Currently, soft robots predominantly rely on fluidic actuators (7), which can be designed to suit a variety of applications (8–10). However, fluidic actuators require a supply of pressurized gas or liquid, and fluid transport must occur through systems of channels and tubes, limiting speed and efficiency.

      Fluid actuators, which converts fluid pressure into movement, were previously used in soft robots. This would make actuators bulky, slow and less efficient because of tanks and channel systems needed to generate the pressure.

    7. This discrepancy in mechanics has inspired the field of soft robotics (1–4), which promises to transform the way we interact with machines and to enable new technologies for biomedical devices, industrial automation, and other applications (2, 5, 6).

      Traditional robots require rigid structures. This has caused design considerations to work around the machines rather than the problem being solved. Soft robotics seeks to eliminate the rigid structure problem.

      Most importantly, for biomedical problems, soft robots provide flexibility and adaptability for accomplishing tasks in a way similar to humans. They also provide a platform for safer interaction with humans.

    8. capacitive self-sensing has been used for closed-loop control of DE actuators (31).

      Capacitive self-sensing is an sophisticated approach to drive actuators in closed loop because it does not require any additional or external sensing elements. A simple proportional integral (PI) controller was used in this work to successfully demonstrate the application of capacitive self-sensing for closed-loop operations, and a tunable grating actuator was used to test the actuation scheme.

    9. capacitance can be measured transiently by applying a low-amplitude AC voltage

      Previous work using an electromechanical oscillator consisting of three artificial muscles was used to measure capacitance by applying low-amplitude AC voltage. Dielectric Elastomer Actuators (DEAs) were used as flexible capacitors. The oscillator supported a set of rails on which a ball was placed. Upon actuation, the rails tilted, rolling the ball.

    1. markedly lower than those observed in humans (27)

      Kook and colleagues studied the plasma levonorgestrel concentrations following the oral administration of Levora tablets in females between the ages of 19 and 44. The mean concentration observed was 14.1 +/- 7.9 ng/mL.

      This data serves as a comparison for the serum concentrations that was observed in the pigs.

      While the drug concentration in the serum is in the range of nanograms/ml in humans, it is in the picograms/ml range in pigs.

    2. reported to be ~1.7 to 1.9 cm (26).

      Dr. Salessiotis experimentally measured the diameter of a fully functioning pylorus. It was concluded that a diameter of 1.9 cm was never exceeded.

      When unfolded, the smart pill spans larger than this reported size.

    3. Using this dosage form, we have shown 1- to 2-week-long delivery of anti-infectious disease agents previously (23, 25); however, month-long delivery of contraceptives has yet to be achieved.

      The authors have previously shown that this smart pill can release drug for infectious diseases for a period of 1-2 weeks. Here, the authors extend this time to 4 weeks for the oral contraceptive application.

  12. Mar 2020
    1. The Cretaceous–Paleogene (K–Pg) boundary marks Earth’s most recent mass extinction, when over 75% of species,

      The boundary is a thin band of rock with a high concentration of platinum (heavy) metals. L. Alvarez et al. hypothesized that this layer resulted from an asteroid impact. Evidence is based on the concentration of these metals in Earth’s crust as compared to their cosmic abundance. The asteroid impact resulted in both the asteroid and rock from Earth’s crust being pulverized and sent as dust into the atmosphere. This dust was distributed worldwide. By sampling deep-sea sediments, Alvarez et al. found that the boundary rock contained higher concentrations of platinum metals than the surrounding Cretaceous and Tertiary limestones, supporting the asteroid impact hypothesis.

    1. Passage of the dosage form from the body was not studied here; although pigs are recognized as having gastric anatomy comparable in dimension to humans, transit times are recognized to be slower (25, 30). Intestinal passage time will not be important to serum drug levels if the dosage form has released all of its contents.

      The passage times of ingested food/drugs through the digestive system is slower in pigs compared to humans. Therefore, before applied to humans, the design of the smart pill should be modified. The smart pill's residence time in the stomach should be lengthened and the period of drug release should be shortened. This design change will ensure that the smart pill releases all its drug content while in the digestive system.

    2. previously applied in weekly oral formulation systems (23).

      Kirtane and colleagues developed a once-weekly oral drug delivery system for HIV medication. The smart pill was unique in its drug-polymer matrices, which allowed week-long drug delivery at the desired concentration.

      This matrix-based system was applied to the smart pill developed in this work.

    3. microneedles are also being developed as a pain-free means of administering long-term contraceptives

      The use of microneedles has been proposed as an alternative contraceptive, which works through applying a pain-free patch that administers hormones at regulated times.

    4. In situ–forming drug depots that are made by injecting drug, polymer, and a safe organic solvent have also been described

      Wu and colleagues reviewed past strategies of developing injectable hormonal contraceptives. Their analysis describes the use of injections to form drug deposits as a long-term contraceptive option.

    5. 40 to 50% of women missed at least one dose. A similar percentage of women reported to have taken the medication at the wrong time (19).

      Hooper studied contraceptive pill users by analyzing the results of an online questionnaire. The attitudes, awareness, compliance, and preferences of users were assessed.

      Analysis revealed non-compliance (failing to take a pill altogether or taking a pill at the wrong time) by many users, including missed doses or doses taken at an incorrect time.

    1. To promote vascularization, we incorporated fibronectin and the proangiogenic molecule recombinant vascular endothelial growth factor (VEGF) into our collagen bio-ink (19)

      Researchers at the Department of Genetics and Pathology in Rudbeck Laboratory studied three vascular endothelial growth-factor receptors (VEGF) responsible for regulating the cardiovascular system. They showed the importance of controlling angiogenetic-growth-factors (such as proangiogenic) that are responsible for the formation of blood vessels. Fibronectin is not mentioned by name but other glycoproteins are emphasized for their importance as receptors for VEGF.

    2. Recently, Dvir and colleagues 3D-printed a decellularized ECM hydrogel into a heart-like model

      Dvir and colleagues used stem cells to print patches of heart tissue and showed that they had functioned properly and contained blood vessels (a sign of healthy tissue). Once they had a process to create the tissue they were able to print a full scale, anatomically correct, functioning heart.

    3. (16)

      Thomas Hinton and colleagues at Carnegie Melon University developed a hydrogel bath in which a syringe injects another gel that solidifies with a precision up to 100 micro-meters. The gel bath was then removed by raising the system temperature from 22°C (71.6°F) to 37°C (98.6°F) while the deposited material simultaneously remained solidified.

    1. white-tailed deer (Odocoileus virginianus) have persisted in the absence of predators for more than a century, causing the successive elimination of saplings of less and less palatable trees and shrubs

      In this study, it was discovered that balsam fir, the island's original dominant tree species, was not able to recruit, as it was a favorite food for deer. White spruce, and several companion species, have replaced the fir, as deer do not find them palatable.

    2. Other examples include the spread of the invasive brown tree snake (Boiga irregularis) on the otherwise vertebrate predator–free island of Guam

      A number of different factors led to the success of the brown tree snake in Guam: barrier-free dispersal, few safe areas for avian prey, lifestyle of the predator (nocturnal and arboreal), and the ability of the predator to find prey under varying conditions.

    3. In contrast, introduced rats (46) and arctic foxes (Fig. 4) (47) have reduced soil fertility and plant nutrition on high-latitude islands by disrupting seabirds and their sea-to-land nutrient subsidies, with striking effects on plant community composition.

      A metastudy of 45 replicated and 35 unreplicated field experiments found that introduced predators had double the negative effect than of native predators on their vertebrate prey:

      Read more: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1950296/

    4. From land, the demise of Pleistocene megaherbivores may have contributed to or even largely accounted for the reduced atmospheric methane concentration and the resulting abrupt 9°C temperature decline that defines the Younger-Dryas period

      Herbivores produce large amounts of methane, a potent greenhouse gas, as a byproduct of their diet. By losing so many of these organisms during the Pleistocene and early Holocene, the methane concentration in the atmosphere would have dropped rapidly, helping to cause the global cooling of the Younger-Dryas.

    5. Further examples of the interplay between predation and disease exist for aquatic systems. The establishment of no-take marine reserves in the Channel Islands of southern California led to increases in the size and abundance of spiny lobsters (Panulirus interruptus) and declines in population densities of sea urchins, which are preyed on by the lobsters. The reduced urchin densities thwarted the spread of disease among individual sea urchins, which led to a lowered frequency of epidemics of sea urchin wasting disease within the reserves

      By allowing the expansion of the predator population (spiny lobster), the size of the prey population (sea urchins) was held in check and individual urchins suffered from disease less often.

    6. The sea otter/kelp forest system in the North Pacific Ocean

      The kelp forests of Alaska and the Aleutian Islands were monitored for up to 15 years to evaluate the impacts of top-down controls by sea otters on the community structure of the region.

    7. For example, empirical research in Serengeti, Tanzania, showed that the presence or absence of apex predators had little short-term effect on resident megaherbivores [elephant (Loxodonta africana), hippopotamus (Hippopotamus amphibius), and rhinoceros (Diceros bicornis)] because these herbivores were virtually invulnerable to predation (24). Conversely, predation accounted for nearly all mortality in smaller herbivores [oribi (Ourebia ourebi), Thompson’s gazelle (Eudorcas thomsonii), and impala (Aepyceros melampus)], and these species showed dramatic increases in abundance and distribution after the local extinction of predators.

      In this study, it was noted that ungulates above 150 kg were regularly limited by food availability instead of predation, due to their large body sizes.

      Conversely, small ungulates (<150 kg) were regular prey of the several large carnivores on the Serengeti, and their populations, and the trophic levels below them, were controlled by the apex predators.

      Loss of predators in these systems caused much greater impacts on the smaller herbivores than the larger ones.

    8. Although the extent and quality of evidence differs among species and systems, top-down effects over spatial scales that are amenable to experimentation have proven robust to alternative explanations

      A metastudy of 41 papers and 60 independent tests found that terrestrial trophic cascades occurred more frequently than previously thought across systems and were on par with those in aquatic environments. While the strength of the cascade response varied across systems based on several factors (type of carnivore, plant antiherbivore defenses, type of damage measured, etc.), trophic cascades were common, although not universal.

    9. The omnipresence of top-down control in ecosystems is not widely appreciated because several of its key components are difficult to observe.

      To see the effects of one such natural experiment, read "Ecological meltdown in predator-free forest fragments," from Terborgh et al. in Science.

      Also can be found in the "Related Content" sidebar.

    10. This empirical work supports long-standing theory about the role of top-down forcing in ecosystems but also highlights the unanticipated impacts of trophic cascades on processes as diverse as the dynamics of disease, wildfire, carbon sequestration, invasive species, and biogeochemical cycles.

      To learn more about the interesting work on the complex impacts of trophic cascades, see research in Science (Ngai & Srivastava, 2006; Chapin III et al., 1997; Myers et al., 2007).

      PDF downloads of these papers can be found under "Related Content."

    11. The loss of these animals may be humankind’s most pervasive influence on nature

      Humans have a number of different impacts on the biosphere, but loss of apex predators is thought to be one of the widest ranging issues of the planet.

      An overview of the threats to the planet's largest 31 carnivores and implications can be found here.

      The study (Ripple et al.) can also be found in the "Related Content" sidebar.

    1. which is comparable to linear strain achieved by biological muscle (26)

      J. D. W. Madden et al. previously reported strain percentages of 20%, which is comparable to the experimental strain of 37% achieved in this paper.

    2. Weibull distribution for dielectric breakdown (19).

      A Weibull distribution works similar to a normal distribution or a grading "bell-curve". In previous experiments, it was shown that the likeliness of a dielectric breakdown is based on a specific Weibull distribution.

  13. Feb 2020
    1. Patient adherence to medications can be increased by reducing dosing frequency (21).

      Iglay, Cao, Mavros, Joshi, Yu, and Tunceli reviewed twenty-two observational studies regarding how often chronic disease patients took their medication. Patients prescribed once-weekly and once-daily doses were compared.

      The analysis showed that patients needing to take doses once a week were more likely to take their medication than patients needing to take doses once a day.

    2. Adherence to monthly therapies is greater than adherence to weekly and daily therapies (22).

      Kishimoto and Maehara studied and compared adherence to daily, weekly, and monthly doses of medication for osteoporosis patients.

      The study revealed that monthly medication regimens had better patient adherence than weekly and daily medication regimens.

    1. (2)

      Researchers 3D printed biological material to create different types of cells and repeated the process in a complex way to replicate testable organs such as livers.

    2. (1)

      Researchers from Center for Nano-scale Systems (CNS) developed a method to 3D print a microchip replicating an organ to test experiments without putting anyone at risk.

    1. North American Land Mammal Age (NALMA)

      This system established a geologic time scale for the emergence of North American land animals beginning with the late Cretaceous and continuing to the present. These ages, or stages when referring to the rock strata, were established using geographic place names to identify where the fossils were found.

    2. magnetochron boundaries

      This refers to the analysis of rock strata to determine remanent magnetization. It provides precise information about the polarity of the Earth’s magnetic field at the time of formation of the strata. The time interval between polarity reversals, or chron, is then used to accurately determine when the change occurred and date the strata.

    3. Taeniolabis taoensis

      They are members of the taxon Multituberculates and are not thought to belong to any of the groups of mammals living today. The anatomy of the pelvis suggests that they did not lay eggs but gave birth to very small, immature young. They had specialized teeth ideal for a vegetarian diet.

    4. A comparable study with similar time bins from the Williston Basin estimated 57% extinction in dicot leaf morphospecies at the KPgE

      Note that the authors' work is built upon the findings of earlier research.

    5. carbonate-clumped isotopes

      This is a way to determine the temperature based on the principle that the formation temperature of carbonate minerals is proportional to the relative abundance of 13C18O16O in CO<sub>2</sub>. The clumped isotope thermometer is based on the measurement of the abundance of 13C-18O bonds in the mineral sample.

    1. Diamonds are physically and chemically robust, allowing retention of He isotope signatures that reflect their formation environment (18–20).

      Multiple investigations have been performed to study the distributions and compositions of helium in a group of well-characterized diamonds. Studies during the 1980s made the scientists aware of the unusually <sup>3</sup>He/<sup>4</sup>He ratio within individual diamonds. More recent explorations indicate that these diamonds are sources of radiogenic helium-4 and are generally found underneath the Earth’s mantle.

    2. An upper mantle location for the high-3He/4He reservoir has also been suggested on the basis of seismic anomalies, heterogeneities sampled by small degrees of melt, and modeled low–U-Th/3He domains formed through melt depletion (1, 12–17)

      Conventionally, a high <sup>3</sup>He/<sup>4</sup>He ratio is known to originate from the lower mantle region of the Earth. However, studies show that this is not always true. A new model proposed by scientists analyzed the seemingly inconsistent results and hypothesized that the high <sup>3</sup>He/<sup>4</sup>He content may also arise from the upper mantle region.

  14. Nov 2019
    1. pulsing dendritic cells with antigen

      The final tumor-specific method of generating immunity is to directly produce dendritic cells (the most common type of antigen-presenting cells) which display tumor antigens.

    2. produce granulocyte-macrophage colony-simulating factor

      Another tumor-specific method of generating immunity is to modify tumor cells so that they produce a molecule which encourages the immune system's professional antigen-presenting cells (APCs) to take up molecules from the tumor cells. This means that APCs are better able to "train" T cells to recognize the signatures of the tumor.

    3. engineering tumor cells to express MHC class II molecules

      Another tumor-specific method is modifying tumor cells so they become more similar to antigen-presenting cells. This allows T cells to recognize them more easily.

    4. induction of B7 expression, rely on enhancing the costimulatory activity of the tumor cells themselves

      One such tumor-specific method of generating an immune response is to modify tumor cells so that they produce costimulatory molecules that enhance activation of T cells they come in contact with.

    5. Current methods of enhancing antitumor immunity generally require the engineering of tumor cells

      There are other methods of generating an immune response against cancer. Unlike this one, they are specific to the type of tumor, and require that the tumor cells be obtained and engineered in some way to become more visible to the immune system.

    6. antigens are most likely transferred to and presented by host

      For the immune system to be able to respond to molecules on the surface of cancerous cells, these molecules are first presented on the surface of specialized immune cells. Through this antigen-presentation process, T cells able to respond to these molecules are activated and expanded.

  15. Oct 2019
    1. However, plastic packaging for food, beverage, and tobacco items is often used only once, which has contributed to 61% of global beach litter

      The Institute for European Environmental Policy found that plastics make up 85% of beach litter worldwide, 61% of which are single-use plastics, such as those used in food packaging.

    1. B7-1 expression was partially successful at inducing rejection

      If cancerous cells express B7-1, the immune system is better able to respond to them and clear the tumor.

    2. CTLA-4 engagement can induce apoptosis in activated T cells

      Another effect of CTLA-4 signaling is the programmed cell death of T cells. This is another way for CTLA-4 to dampen T cell responses.

    3. greatly augment T cell responses to nominal peptide antigen or the superantigen Staphylococcus enterotoxin B in vivo

      Blocking CTLA-4 also increases T cell activation that happens as a result of encountering foreign invaders.

    4. enhances proliferative responses

      The inhibitory CTLA-4 receptor can be blocked by using soluble antibody. Blocking the effects of CTLA-4 allows T cells to activate and proliferate normally upon induction by anti-CD3.

    5. induced by antibody to CD3 (anti-CD3)

      CD3 is a co-receptor alongside the T-cell receptor. Together, they provide the primary signal of T cell activation. In this experiment, the scientists tried to add anti-CD3 antibody, which would normally result in T cell activation. However, the inhibitory effect of CTLA-4 wins out over this activation technique.

    6. binds both B7-1 and B7-2 with affinities much greater than does CD28

      CTLA-4 competes with CD28 for binding to the B7 family of molecules.

    7. costimulation is more complex than originally thought and involves competing stimulatory and inhibitory signaling events

      The overall activation of T cells is also influenced by another type of secondary signal. In addition to stimulatory signals discussed above, T cells may also encounter inhibitory signals. The balance of these two signaling events results in the overall level of activation.

    8. tumor cells expressing costimulatory B7 molecules induced potent responses against both modified and unmodified tumor cells

      Introducing the genes for B7 molecules into tumor cells allows them to provide the secondary signal needed to activate T cells. This allows the immune system to respond to those modified tumor cells, as well as any future tumors of the same type that they encounter (even if the latter do not express B7).

    9. appears to be provided by the interaction of CD28 on T cells with its primary ligands B7-1 (CD80) and B7-2 (CD86) on the surface of specialized antigen-presenting cells (APCs)

      The two-signal model of T-cell activation was confirmed when scientists found that specialized immune cells, called antigen-presenting cells, provide a secondary signal to T cells in order to activate them. This secondary signal comes from the interaction of the B7 family of molecules (on the surface of APCs) with the CD28 receptor (on the surface of T cells).

  16. Sep 2019
    1. In recent experiments, Dienwiebel et al. (8) observed friction reduction to vanishingly small values, depending on the degree of commensurability between the graphene flakes and the extended graphite surface

      The mechanism of superlubricity at the sliding interfaces of materials is studied. Dienwiebel and co-researchers have investigated the superlubricity of graphite using a home-built frictional force microscope. They have also investigated the role of incommensurability in the origin of the ultralow friction of graphite.

    2. The contact area, which is proportional to the number of interacting atoms, reduces by 40 to 50% during (26) this period.

      Size plays a major role in superlubricity and many researchers have investigated the dependence of size of materials in friction reduction. Liu and co-workers reported one such size-dependent study of superlubricity on graphite. They have detailed the probability percentages of the superlubric state for different contact areas and also the mechanism of superlubricity (self retraction) of graphite layers.

    3. Even a modest 20% reduction in friction can substantially affect cost economics in terms of energy savings

      The failure of moving mechanical assemblies due to friction and wear is a major concern in today's world. Different types of lubricants are employed to minimize friction. Though this helps to improve the lifetime of mechanical systems, researchers are on a quest to find a perfect lubricant to achieve the lowest friction and wear possible with no harmful additives or chemicals.

    4. To date, superlubricity has been primarily realized in a limited number of experiments involving atomically smooth and perfectly crystalline materials (2–5) and supported by theoretical studies (6, 7).

      Research in superlubricity is gaining interest due to its potential applications in mechanical systems to reduce friction- and wear-related failures. Various researchers proposed different materials to achieve near-zero friction. Even though these materials show some promise, most materials are perfectly crystalline (which is not the case in real life) and the effect occurs mostly at the nanoscale regime.

    5. with the previously observed low-friction performance of DLC against DLC (fig. S14) (12)

      Diamondlike carbon (DLC) film is a widely researched material to combat friction and wear in a number of applications, owing to its impressive tribological properties and low deposition costs. The tribological properties of DLC films sliding against each other are investigated and they are found to display super-low friction under specific conditions.

    6. The π* peak (at ~285 eV) in the carbon K-edge represents a small fraction of sp2 bonded carbon owing to the presence of the few layers of graphene wrapped around the nanodiamond, which is similar to the disordered carbon shell observed previously in detonated nanodiamonds (23)

      The structural analysis of graphene-wrapped nanodiamonds by electron energy-loss spectra (EELS) reported in this study is analogous to the previously reported structure of detonated nanodiamonds by other researchers.

    1. Stimulation of anorexigenic proopiomelanocortin (POMC) cells in the hypothalamic arcuate nucleus leads to a reduction in feeding slowly over the succeeding 24 hours, whereas stimulation of orexigenic hypothalamic neurons expressing agouti-related peptide (AgRP) leads to what has previously been considered to be a rapid increase in feeding with mean latency to eat of 6.1 min (range: 1.9 to 13.8 min) (19).

      The arcuate nucleus, a subregion of the hypothalamus, has been shown to be a very important brain region that controls food intake

      Neurons within this region have been shown to control feeding in a reciprocal manner. POMC-expressing neurons are activated by satiety signals and reduce food intake whereas AgRP-expressing neurons are activated by starvation and increase food intake. These neurons have been proposed to be the neural substrate for satiety and hunger, respectively.

  17. Aug 2019
    1. Despite the relatively well-studied pathway of fructose metabolism in the liver and in the small intestine, the role of fructose metabolism in tumors is mostly unknown.

      This paragraph details the pathway of fructose and glucose metabolism within cells. In normal cells this is how glucose and fructose are broken down and converted into energy. It is unknown how tumors metabolize these molecules and so the scientists move on to explore this in their next series of experiments.

    2. Similar results have been reported for other fructose-metabolizing enzymes, ketohexokinase (KHK) and aldolase B in human colon tumors (22, 23).

      Colorectal tumor fructose metabolism has been looked at in the past. In these studies the enzymes required to break down fructose were studied, rather than looking at fructose transporters as this paper did. The past research found similar results where tumors had higher levels of enzymes that break down fructose than normal human tissues did.

    3. Relatedly, a recent study in mice showed that fructose doses greater than 1 g/kg (~1% of daily calorie intake) overwhelm fructose absorption in the small intestine, resulting in a higher concentration of fructose in the colon (20)

      The same results seen in human studies looking at gastrointestinal discomfort after fructose consumption were recapitulated in mouse studies. In animal models scientists are able to more closely control variables and more inversely monitor outcomes. In this case they were able to directly measure fructose concentrations in the colon rather than relying on gastrointestinal symptoms. They found high concentrations of fructose in the colon after oral delivery, suggesting that the passive transporters in the intestine were unable to uptake fructose at levels higher than 1g per kg of weight.

    4. The consumption of as little as 5 g of fructose can lead to the saturation of GLUT5 in the small intestine (i.e., malabsorption), resulting in an increased concentration of fructose in the lumen of the colon (large intestine) of healthy humans (17–19)

      A past study administered various amounts of fructose to people after fasting. They then assessed gastrointestinal symptoms that stem from fructose passing through into the intestines and colon undigested (malabsorption). They found that even 5g of fructose can lead to the saturation of passive transporters in the intestine. Ingestion of any amount of fructose over 5g will result in high levels of fructose in the colon.

    5. We observed similar results in a study of another mouse model, CDX2P-CreERT2; APCflox/flox (fig. S3, D to H), where intestinal tumors develop mainly in the colon instead of the small intestine (15).

      Previous study of another genetically modified mouse model (where tumors were induced to grow mostly in the colon) demonstrated similar results. This suggests that this mouse model or genetic manipulation (APC deletion) itself is not somehow more sensitive to high fructose corn syrup than other mutations that lead to colorectal cancer. Comparing previous results increases confidence that any colorectal cancer tumors will respond to high fructose corn syrup in a similar fashion.

    6. tumor suppressor that is frequently mutated (75 to 80%) in the early stages of CRC development (13).

      Scientists have found that in a high majority of colorectal cancers the APC gene is defective. This high correlation suggests that the APC gene is a major cause for the development of colorectal cancer and tumors.

    7. Indeed, studies have shown that excessive consumption of SSBs causes obesity and that being obese increases the risk of CRC, especially in men

      Taking big data sets such as questionnaires or patient data, computational biologists can run statistical tests to look at correlations between variables. In this case data has shown that people who drink a lot of sugar-sweetened beverages (such as soda) tend to be more overweight and in men there was a significant correlation to developing colorectal cancer.

    1. sympathetic superior cervical ganglion in adult rats

      Prior to this research, studies primarily focused only on the transmitter expression during development. Is there a similar phenomenon in adult stages? The cervical ganglia are separated by denervation technique. The denervated ganglia were measured for the activity of substance P. Two-fold increase in substance P was observed in the ganglia compared to controls.

    2. Since some trigeminal neurons are derived from the neural crest, whereas nodose neurons are epibranchial placode derivatives, heterogeneous populations, differing embryologically, geographically, and functionally, may exhibit transient catecholaminergic expression during development.

      Two types of neurons—trigeminal neurons and nodose neurons—are discussed here.

      Trigeminal neurons are derived from the neural crest. Epibranchial placodes help in the generation of the neurons found in the back of the brain/cranial nerves (or nodose). Hence, both neurons differ in embryonic origin.

      Trigeminal neurons are derived from one source and hence they are homogenous. However, the epibranchial placode helps in the generation of several cranial nerves, namely hypoglossal and glossopharyngeal. This results in a heterogenous population.

      As both sets of neurons differ in their embryonic origin and location in the brain, it is fair to state that the functions of these neurons to express catecholamines will also be different.

    3. phenotypic alteration may be mediated, at least in part, by specific hormones and alteration in the processing of specific species of mRNA

      The conversion of norepinephrine to epinephrine is dependent on the mRNA synthesis and hormones released by the pituitary-adrenal axis.

    4. Consequently, these neurons may convert from catecholaminergic to cholinergic and peptidergic during development

      Neurons in rat sweat glands can convert from catecholaminergic to cholinergic groups during development. This is evident from the lack of enzymes that are responsible for catecholamine synthesis.

  18. Jul 2019
    1. Although bulk transcriptomic tissue studies revealed convergence of disease pathology on common pathways (1–3)

      These studies performed RNA sequencing to identify differences in RNA and gene expression in the autistic brain. They found that there are similarities in the kinds of genes that are changed in patients with autism.