1,015 Matching Annotations
  1. 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.

  2. 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

  3. 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. 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 where 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 the CTLA-4 signaling is inhibition of T cell activation and expansion.

    2. 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.

    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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Nov 2019
    1. 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 was shown to dictate the types of networks that dominated those areas

    2. 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'au, experienced severe changes in comparison to before the arrival of humans.

    3. By contrast, the architecture and stability of novel interaction networks across spatial scales and how they compare to native-dominated communities remain virtually unknown. This knowledge gap hampers our ability to forecast and mitigate the impacts of extinctions and invasions on ecosystem functions

      The authors note that research in the field has been limited to interactions between local species, neglecting the networks involving new, introduced species. Understanding the latter point will aid in efforts combating negative effects on ecosystems.

    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, ant 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 the growing diversity and coexistence of multiple species in an ecosystem.

    5. 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 (grey arrows).

    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.

    7. 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 of publishing of this paper, it was not clear why this was the case.

  9. 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. 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. 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.

    4. 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.

    5. 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.

    6. 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.

    7. 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.

    8. 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.

    9. 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).

    10. 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).

  10. 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.

  11. 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.

  12. 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.

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

      KDM6B activation of genes critical for early developmental processes, such as gonad specification and body patterning.

    2. 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 genes.

      Female-producing temperatures specifically lead to de-methylation and addition of activating histone marks to the promoter for the gene encoding the enzyme that produces estrogen in turtles, alligators, and sea bass.

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

      H3K27me3 is a histone mark that recruits repressive factors to that region of DNA, essentially silencing any local gene expression.

    4. 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 turtle embryos at male- and female-producing temperatures to identify differences in gene expression that drive sex development.

      Kdm6b was one of six genes consistently upregulated at male-producing temperatures. KDM6B was likely chosen for a follow-up study due to its potential to regulate the expression of multiple male development genes.

    5. 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

      As opposed to the genome conferring sex as it does in vertebrates (e.g. XX confer female development and XY leads male development in many mammals), the ambient environment determines sex for some organisms.

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

    1. 22

      In this study, Professor Arnold's group used protein engineered variants of cytochrome P450BM3 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 diasteromers 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. 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 different pairwise interactions, along with species abundance.

    2. High interaction dissimilarity has also been reported in specialized, native-dominated pollination networks, even between spatially close networks (33)

      D. Carstensen and others quantified the variability of interactions between plants and pollinators across different spaces. They found that these interactions vary greatly between different locations due to the abundance of species, which determined the likelihood of partners interacting with each other.

  13. Jun 2019
    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.

      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.

    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 there 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 towards any particular plant(s). When the obligate frugivores eat from a wide variety of plants, they are utilizing the majority of interactions available in their ecosystem- demonstrating high connectance. There are also no particular groups of plants that the frugivores specifically associate with, an example of a nonmodular structure.

    3. For example, both fleshy-fruited plants and frugivores on islands tend to have wide niches owing to resource limitation

      Traveset and colleagues observed that bird-plant interactions on the Galápagos islands are highly generalized, meaning the birds developed relationships with a wide variety of plants, and vice versa. These broad interactions offer more opportunities for species to gain food. However, the authors also warn that these additional interactions promote the reproduction and survival of invasive plant species, at the cost of native species.

    4. 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 dispensers (aka birds) is an important factor regarding the survival of native Hawaiian plant species. One study showed that the distribution of seeds from native plants are 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.

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

      A mutualistic network is a beneficial partnership 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.

    1. reduce the gender gap in college physics classrooms (13)

      Lorenzo, Crouch, and Mazur found that using more interactive teaching methods improved conceptual understanding for all students in a college-level physics class and reduced the gap in performance between women and men, compared to classes taught in the traditional lecture-based way. Classes taught with the highest level of interaction eliminated the gender gap.

    2. affect performance in lab experiments and classrooms (20

      Schmader, Johns, and Barquissau found that women who identified more strongly with the stereotype that men are better than women at math were likely to be less confident about their own abilities and less likely to pursue math careers. They also found that women who believed the gender stereotype were more susceptible to its negative effects on math test performance.

    3. improve the performance of stereotype-threatened individuals

      Values affirmation can reduce the effect of stereotype threat for women taking a math test under laboratory conditions.

    4. lab studies show

      It has been shown that values affirmation can significantly reduce a person's physical response to a subsequent stressful situation.

      Specifically, participants that performed a values affirmation task before undergoing a stress test produced less cortisol (a hormone that is released when we are stressed) than participants who did not get the intervention.

    5. can account for as much as 60% of the gender gap in exam performance at our institution, the University of Colorado, but background and preparation do not fully account for the gap (9)

      Previous work has assessed the gender achievement gap in college students taking introductory physics at the University of Colorado at Boulder.

      Despite the use of teaching methods thought to reduce the gender achievement gap, there remained a difference between men's and women's test scores. Most of this gap could be attributed to differences in prior preparation (for example, men were more likely to take high school physics), but not all of the gap could be attributed to these factors.

    1. a ganglionic blocking agent that prevents depolarization by competing with acetylcholine for postsynaptic nicotinic receptors, reproduced the effects of denervation

      Using a blocking agent for nicotinic receptors, the binding of acetylcholine was blocked in the ganglia. This manipulation is similar to denervation technique and hence, the authors observed an increase in the activity of substance P.

    2. the high-affinity uptake system for α-CH3-norepinephrine (5), a characteristic of noradrenergic neurons

      The uptake of norepinephrine in these neurons remain unaffected. The neurons are capable of producing noradrenaline.

    3. Sympathetic neurons innervating rat eccrine sweat glands appear to convert from noradrenergic to cholinergic

      Noradrenergic neurons produce norepinephrine, the neurotransmitter expressed in rat sweat glands during postnatal stages of development. For a short period of time in development, the neurons lose the noradrenergic expression, but pick up the expression of acetylcholine.

    4. Recent work with bullfrog sympathetic ganglia suggests another mechanism for alteration of site of transmitter action.

      Previously, researchers found that neurons in frog sympathetic ganglia are also depolarized by substance P, making them an appropriate model organism to study.

    1. In brain slices taken from the striatum, we measured LTP in the excitatory synapses (in the cortico-accumbens pathway) in the NAc core (Fig. 2A), known to be reduced in response to chronic cocaine administration

      Cocaine is capable of producing LTP in several brain regions.

    2. This result is consistent with our earlier finding that SAHA caused a marked increase in FosB expression when given before an acute cocaine injection compared with the effect of cocaine alone

      Similar to nicotine, SAHA also causes an increase in the expression levels of FosB

    3. SAHA helps restore some of the memory deficits in these mice

      In cocaine-treated animals, LTP is impaired. SAHA helped in rescuing certain aspects of LTP in cocaine-treated animals.

    4. Thus, most cocaine users smoked cigarettes before they started using cocaine, and, in addition, they started using cocaine while they were actively smoking cigarettes

      This study shows that the key determinants for sequential drug use are the onset of age and the frequency of drug usage

    5. Because an important step in the molecular sequence leading to the expression of the addictive phenotype in mice is increased FosB expression in the striatum

      The authors use DNA expression array techniques to identify genes that are modified by drugs of abuse and their mechanism of action.

      FosB is shown to regulate gene expression in cocaine-treated animals.

    6. The addiction process is also mediated through histone acetylation of the promoter of the transcription factor ΔFosB

      CBP is instructed to FosB promoter to acetylate H4 histones, thereby regulating the expression of FosB gene in cocaine-treated animals

    7. An acute cocaine injection increases acetylation of histone H4 but not H3 at the FosB promoter

      This paper shows that chromatin remodeling is a key mechanism that contributes to cocaine-induced synaptic plasticity.

      Here the authors show that the cocaine can cause acetylation of histones via histone acetyl transferase (HAT) at a particular promoter site leading to chromatin acetylation and remodeling.

    8. the consequent activation of a downstream cascade of gene expression initiated by CREB [cyclic adenosine 3′,5′-monophosphate (cAMP) response element–binding protein]. This cascade is dependent upon the acetylation of histone tails by the CREB-binding protein (CBP), a histone acetyl transferase (HAT)

      The authors show that the impairment in LTP and chromatin acetylation was observed in the animals.

      By manipulating the CREB binding protein (CBP), some of these deficits were able to be restored. This suggests that LTP depends on the regulation of CBP.

    9. The molecular pathways involved in addiction share some of the same molecular logic and even some of the same molecular steps encountered in long-term memory storage

      Cocaine induces long term depression (LTD), a form of synaptic plasticity in the nucleus accumbens. This impairment in LTD causes deficits in the memory storage in this brain region.

    10. Reduction of excitatory input to the NAc is thought to decrease inhibitory output from the NAc to the VTA and thereby contribute, through disinhibition, to the increased reward and enhanced locomotion activation observed after cocaine administration

      After administering cocaine to animals, there is a decreased excitatory input from the prefrontal cortex to Nucleus accumbens.

      This change in inputs leads to a lack of restraint on the inhibitory output from the nucleus accumbens to the ventral tegmental area, as the inhibitory output remains the same.

      This leads to increased dopaminergic activity in VTA, leading to an increase in motor activity and in reward pathways.

    11. For example, in 2009 in the United States (4), among adults aged 18 to 34 who had used cocaine at least once, 90.4% had smoked cigarettes before they began to use cocaine, 4.7% began using both drugs at the same age, 2.4% used cocaine first, and 2.5% had never smoked

      This survey was conducted in the US to identify the usage and correlation of drugs of abuse. Questions were provided as a survey to the participating individuals, and the results are summarized in the report.

      Examples of queries are age, drug usage, and frequency, lifestyle, smoking, and drinking frequency.

    1. Tipping points (also known as thresholds or breakpoints), around which abrupt changes in ecosystem structure and function (a.k.a. phase shifts) occur, often characterize transitions between alternative stable states.

      These tipping points are notoriously difficult to predict but can be recognized after the fact. Models are being developed to identify tipping points ahead of time, for example here.

    2. The history of life on Earth is punctuated by several mass extinction events (2), during which global biological diversity was sharply reduced. These events were followed by novel changes in the evolution of surviving species and the structure and function of their ecosystems. Our planet is presently in the early to middle stages of a sixth mass extinction (3), which, like those before it, will separate evolutionary winners from losers.

      There have been five mass extinctions on Earth in the past. These were caused by various natural events, from gamma-ray bursts to megavolcanic eruptions to meteor strikes. During each mass extinction, species diversity diminished significantly in a short period of time. Each mass extinction was followed by the evolution of novel forms of organisms that transformed their habitats in new ways.

      Most scientists agree that we are currently in the 6th mass extinction event, this one largely caused by human activities such as climate change, habitat loss/fragmentation, pollution, invasive species, and human consumption/overexploitation.

    3. Such interdependencies are well illustrated in East Africa, where the introduction of rinderpest in the late 1800s decimated many native ungulate populations, including wildebeest (Connochaetes taurinus) and buffalo (Syncerus caffer). Reductions of these large herbivores caused an increase in plant biomass, which fueled wildfires during the dry season. Rinderpest was eliminated from East Africa in the 1960s through an extensive vaccination and control program. Because of this, wildebeest and buffalo populations had recovered to what was thought to be historically high levels by the early 1980s. The resulting increase in herbivory drove these systems from shrublands to grasslands, thus decreasing the fuel loads and reducing the frequency and intensity of wildfires

      This top-down forcing by disease and loss of herbivores has also been linked to the complex carbon cycle in the region:


    4. For example, the reduction of lions and leopards from parts of sub-Saharan Africa has led to population outbreaks and changes in behavior of olive baboons

      In this case, the apex predators have been overhunted by humans for bushmeat, for trophies, or as pests to their livestock.

    5. A similar result, involving different species and processes, occurred in India, where the decline of vultures also led to increased health risks from rabies and anthrax

      Because of overuse of antibiotics in livestock, the vulture population declined, leading to more scavenging by feral dogs of carcasses throughout the region. As the dog populations grew, and due to their proximity to humans, the risk of transmission of rabies to humans has increased greatly.

    6. In freshwater systems, the localized rise and fall of human malaria is associated with the impacts of predatory fishes on planktivores, which are in turn important consumers of mosquito larvae

      In this case, researchers found that certain types of predatory fish, while consumers of mosquito larvae, also regularly consumed the mosquito's main predators, leading to increased malaria infections.

    7. For example, the reintroduction of wolves to Yellowstone National Park has reduced the positive indirect effects of ungulates on soil nitrogen mineralization and potentially the nitrogen supply for plant growth

      Researchers found that after wolves were reintroduced to Yellowstone, there was a net decline in soil nitrogen, likely due to fewer large herbivores. In addition, the spatial nature of nitrogen renewal changed due to new use patterns by the herbivores.

    8. predatory seastars in the rocky intertidal

      Predatory sea stars regularly graze the rocky intertidal regions and are not prey-specific. Their grazing opens new substrate for multiple species, preventing the dominant species from colonizing all of the rocks.

    9. mesopredator release [coyotes (Canis latrans) maintaining small vertebrate species in chaparral habitats

      It was observed that the loss of coyotes as an apex predator control on smaller vertebrate predators, along with habitat fragmentation, led to trophic cascades in the ecosystem.

  14. May 2019
    1. That the PSTh may be involved in feeding is suggested by increased c-fos expression in the PSTh during anorexia induced by amino acid deficiency

      Anorexia induced by dietary deficiency in a single indispensable amino acid was found to induce expression of c-fos—a protein known to be present in active neurons—in the PSTh.

    2. can exhibit characteristics of binge eating (1–3)

      Zahodne, Amami, and Novakova studied Parkinson's patients and found that many subjects exhibited binge-eating behavior. Those that had received deep-brain stimulation of the subthalamus were more likely to display this behavior.

    3. sheep may release γ-aminobutyric acid (GABA) from the ZI in response to the sight or ingestion of food (6, 7).

      Kendrick and colleagues found that the neurotransmitter GABA was increased in the ZI in sheep when the animals were presented with and ingested food.

    4. These results are consistent with an early report that lesions in the area of the ZI can alter food intake (18).

      The ZI has been shown to be important for food intake that occurs in response to low levels of blood glucose. Rats with ablated ZI eat less food under these conditions.

    5. much-studied lateral hypothalamus

      The lateral hypothalamus is a region neighboring the ZI. Stimulation of this site has been shown to substantially increase food intake and is also hedonic.

    1. Moreover, there is preliminary evidence (9) which suggests that secondary structure within a polynucleotide inhibits the power to stimulate protein synthesis.

      Nirenberg and co-workers saw that poly A was not decoded, specifically at low pH (acidic environments). At low pH, poly A is double stranded. These results suggest that the residues may need to be exposed—that RNA must lack secondary structure—to be decoded.

    2. It is believed, not that DNA itself controls protein synthesis directly in a cell in which DNA is the genetic material, but that the base sequence of the DNA - probably of only one of its chains-is copied onto RNA, and that this special RNA then acts as the genetic messenger and directs the actual process of joining up the amino acids into polypeptide chains. The breakthrough in the coding problem has come from the discovery, made by Nirenberg and Matthaei (6)

      Nirenberg and Matthai discovered that "special RNA"—now called tRNA—was critical to protein synthesis. A protein could only grow with enough tRNA available, demonstrating that tRNA was a critical material to generate proteins.

      To hear a contemporary scientist give an in-depth account of protein synthesis, watch Johns Hopkins University's Rachel Green detail the process on this iBiology video.

    3. For example, something very like rabbit hemoglobin can be synthesized in a cell-free system of which part comes from rabbit reticulocytes and part from Escherichia coli (5). That this would be the case if the code was very different in these two organisms is not very probable.

      Lippman and Von Ehrenstein showed that genetic material (mRNA) from a mammal could be decoded with genetic material (tRNA) from a bacteria to form the protein hemoglobin. Because hemoglobin is not found naturally in bacteria but is found naturally in mammals, this was a remarkable result: The biological material of a bacterium decoded mammalian genetic material!

      The result suggests that vastly different biological species share a genetic language. This is strong evidence that the code is universal.

      See a visualization here.

    4. action of nitrous acid and other chemicals on trick tobacco mosaic virus (2)

      Tsugita used an acid (nitrous acid) to chemically mutate RNA. The acid most often changed cytosine bases into uracil bases. The mutant genetic material encoded a different amino acid sequence than the unmutated, or native, form.

    1. Previous field studies have documented rare but recurring introgressive hybridization on Daphne Major between medium ground finches and small ground finch immigrants (23)

      Introgression, the movement of a gene from one species into the gene pool of another, has been known to speed up a population's response to an evolutionary selective pressure. It does this by increasing genetic diversity.

      Grant and Grant documented recurring introgressive hybridization between medium ground finches and small ground finches.

    1. the REPAIR system directly deaminates target adenosines to inosines and does not rely on endogenous repair pathways to generate desired editing outcomes.

      This is an advantage over the traditional CRISPR/Cas9-mediated genome editing. CRISPR/Cas9 uses the cell's machinery to make changes, so it is efficient only in actively dividing cells.

      Moreover, we can compare the REPAIR system to DNA cytidine base-editors (BE). The BE system has been modified to prevent cellular DNA repair processes that are triggered by Uracil (U) bases in DNA. The BE system, in any form, still relies on DNA repair machinery to propagate the edit. RNA editing does not. 

      Check out the schematic below for more information on the BE editing paths.