1,152 Matching Annotations
  1. Last 7 days
    1. in a manner conceptually similar to that of other recently reported classes of bioresorbable sensors and therapeutic systems to monitor and accelerate wound healing or recovery processes

      Earlier studies have utilized bioresorbability to address similar problems associated with the removal of implantable sensors. The sensors can be designed to begin dissolving immediately after implantation, but remain functional for some time until the main components disintegrate. The duration of the dissolution process can be controlled by the type and thickness of materials within the device.

    2. Analgesic nerve cooling requires spatiotemporally precise control of temperature to maximize desired outcomes and to minimize the chance of cooling-induced tissue damage

      In a prior investigation, researchers simultaneously cooled two sciatic nerves, which extend from the hip to just below the knee, using different methods: one continuously and the other intermittently, for the same duration. They observed a significant discrepancy in response between the two nerves; specifically that though some tissue damage was caused by both intermittent and continuous cooling, the intermittent cooling caused much more severe tissue damage. This suggests that the response of sensory nerves to cooling is highly dependent on the cooling procedure and duration of exposure.

    3. Local cooling of peripheral nerves decreases conduction velocity and signal amplitude of neural activity

      Peripheral nerves are the nerves outside of the brain and the spinal cord, extending through the rest of the body such as the arms and legs, and are responsible for sending and receiving information to and from the brain.

      Cooling specific areas of the peripheral nervous system can cause a decrease in the speed of electrical impulses through the nerves and the strength of those impulses, making it more difficult for pain signals to reach the brain. Therefore, if the author can achieve contained, consistent cooling of certain nerves, they can prevent/reduce pain in patients.

    4. metabolic, electrogenic, and ionic activity in neural tissue all exhibit a negative temperature dependence

      This paper builds on research indicating that when the nerve environment cools down, the activity generating and transmitting nerve impulses decreases, thereby inhibiting the transmission of pain signals to the brain.

    5. Miniaturized implantable devices that eliminate pain signals locally in peripheral nerves suggest a potential role for engineering-based treatments that avoid side effects associated with opioids

      In past research, scientists have used peripheral nerve stimulation (PNS). This involves applying an electric field to certain areas of the spinal cord that send sensory signals to the brain. The electrical stimulation disrupts the nerves responsible for transmitting pain-related sensory information.

  2. Feb 2024
    1. Blocking of transmission of compound action potentials in mammalian nerves typically occurs below 15°C (12), but this threshold can be temporarily increased to near room temperature by a brief heating period preceding the cooling period

      Previous studies have shown that electrical impulses in the nervous system can be blocked by lowering the temperature to 15°C or less, however, if the area is briefly heated, then this cooling threshold can be increased to around 21°C, or room temperature.

    2. The controlled input of electrical (4), pharmacological (5), optical (6), mechanical (7), or thermal (8, 9) stimuli to neural tissue can lead to local and reversible neural blocking

      Local and reversible neural blocking is simply the idea of stopping nervous system signals in a very small spot and being able to do it such that those nerves can be used again once preventing pain is no longer necessary. Pain plays an important role in indicating to the brain that there is something wrong with the body, so it is crucial that any operation that inhibits pain signals can be undone.

      Various studies have been done showing that different types of therapies can be used for local and reversible neural blocking. For example, infrared light can be used to target a very small area and prevent axons from firing, and once the space is cooled down, it returns to normal. Another example might be using sound to change the signals moving to the brain, as ultrasound technology is able to easily move through the body and interact with the nervous system.

    1. more than 300 times smaller than the smallest previous microfermentor (7)

      Zanzotto et al had developed a microscopic bioreactor for carrying out bacterial fermentation. Their device had sensors measuring 2 mm in diameter and can hold a volume as low as 5 µL, compared to the 500 mL of a typical bioreactor.

      Here, the authors further miniaturized their bioreactor volume down to the nanoliter range/scale. For reference, 1 microliter is one millionth of a liter, while 1 nanoliter is one billionth of a liter.

    2. By continually substituting a fraction of a bacterial culture with sterile nutrients

      Research from as early as the 1950s has found that different properties of bacteria can be studied by creating a stable environment with a constant source of nutrients. This has been backed up with mathematical models and led to the creation of the chemostat.

    3. have pushed the move toward miniaturization and chip-based control (7–10)

      Starting with Kim and Lee, researches are pushing towards smaller, more compact bioreactors for the benefits of miniaturization, which include using less resources, reduced costs, and benefiting from physics at the micro/nano scale.

  3. May 2023
    1. Lnp1 is an ER protein that resides at and stabilizes the three-way junctions that form when two tubules fuse to each other (23). In its absence, ER network rearrangements are disrupted and Atg40 puncta fail to access the autophagy machinery (17). As a consequence, ER is not packaged into autophagosomes in lnp1Δ cells

      Lnp1 is a protein to maintain the structure of ER by stabilizing rearrangements of the ER networks.

      Further reading: https://doi.org/10.1073/pnas.1805032115

    2. ER-phagy receptor Atg40

      Protein recycling and self-eating process that selectively happens in endoplasmic reticulum terms as ER-phagy (phagy means eating). Selective autophagy requires a receptor protein to recognize its degradation targets and directs the targets to be sequestrated by autophagosomes, a double membrane vesicle structure, which to be transported into lysosomes or vacuoles.

      A protein named as Atg40, has been recognized as a ER-phagy receptor protein in yeast. FAM134B is a putative mammals homologue of ATG40.

      Literature first explain the Atg40 ER-phagy receptor https://doi.org/10.1038/nature14506 (ATG40)

      https://doi.org/10.1038/nature14498 (FAM134B)

    3. we found an unexpected role for Lst1-Sec23 in ER-phagy that was independent from its function in secretion.

      Lst1-Sec23 is a coat adaptor protein that carry the cargo molecules form ER to Golgi, which mainly to help the secretory proteins transportation. The author discovered new function of the Lst1/Sec23 in self-eating and protein recycling process (autophagy), in which the Lst1-Sec23 functions together with the autophagy receptor, Atg40, to localize the ER domains for autophagic degradation.

  4. Apr 2023
    1. Improved tissue organization can be promoted by growing cells in three-dimensional

      In this paper, Pampaloni et. al discuss how the standard growth of cells on 2 dimensional surfaces does not accurately model organ-level functions such as nutrient/waste transportation. Contemporary research has worked on making 3D cell cultures made of cells and connective tissue, but no one has integrated multiple cell types with connective tissue in an "organ on a chip." In the end, the authors discuss the potential for microdevice technology to address the need for physiologically-relevant organ models in drug screening experiments.

  5. Mar 2023
    1. involve a highly coordinated multistep cascade, including epithelial production and release of early-response cytokines, activation of vascular endothelium through up-regulation of leukocyte adhesion molecules [e.g., intercellular adhesion molecule–1 (ICAM-1)], and subsequent leukocyte infiltration into the alveolar space from the pulmonary microcirculation (28–30)

      When a human gets a lung infection, neutrophils are quick to respond to the infected site and ICAM-1 is over-expressed. These previous sources all characterize this aspect of the immune response of a lung infection. The migration of neutrophils and the expression of ICAM-1 inspired the authors as they tested the efficacy of the lung-on-a-chip. For example, the authors use TNF-a to trigger an immune response and measure the expression of ICAM-1 and presence of neutrophils at the exposure site

    2. these methods still fail to reconstitute structural and mechanical features of whole living organs that are central to their function.

      Pampaloni et. al. discuss the impact that extracellular matrix (ECM) has on cellular growth and development. The three-dimensional distribution of cells in an organ affects how cells--and even other organs--communicate with each other. In this way, "form fits function:" the physical characteristics of a set of tissues can dictate how nutrients and other biomolecules transport between cells. Drug screening is primarily performed on 2D cell cultures, where the functions of human tissues are not accurately represented. This work aims to directly address this issue

    3. in conjunction with a new method that uses chemical etching of PDMS (22) to form the vacuum chambers.

      Takayama et. al report a new way of manufacturing microchannels out of PDMS that can be smaller than the width of a human hair! The process involves the controlled washing of a PDMS slab with chemicals. The authors have high hopes for their technology: "We believe that these procedures will enable new types of studies in fundamental cell biology, and that they will also be useful in the microfabrication of devices that require a high-level of control over the behavior of cells"

    4. Microscale engineering technologies first developed to create microchips, such as microfabrication and microfluidics, enable unprecedented capabilities to control the cellular microenvironment with high

      The following research papers discuss the potential for microfluidic devices to assess the problems with modern 3D tissue models. For example, Langer et al. discuss how standard cell cultures cannot replicate the repetitive mechanical strain that human organs such as lungs and gut undergo every day. The authors also discuss how oxygen and protein transport through these tissue scaffolds does not accurately mimic human conditions. While attempts have been made to improve cell-cell connectivity and nutrient transport in 3D cultures, microfluidic technology provides a potential pathway to generate accurate and viable organ models.

  6. Feb 2023
    1. perhaps to avoid growth in compacted soils

      Montagu et al. reveal that the position of soil compaction affects root growth. When roots grow through compacted soil into uncompacted soil, total root growth is reduced. However, when roots grow through uncompacted soil into compacted soil, more compensatory root growth happens in the uncompacted soil and total root growth is not changed. This suggests that roots can sense soil compaction and avoid growing in compacted soil.

    2. (9)

      An and colleagues revealed that loss of EIL1 suppresses response to ethylene in Arabidopsis.

    3. (13)

      Alonso and colleagues characterized an ein2 mutant in Arabidopsis and found that ein2 mutant did not respond to ethylene.

    4. (12)

      Ma and colleagues identified a rice mutant that cannot respond to ethylene. They found that the mutation happened in a gene encodes a protein that is homologous to the EIN2 protein in Arabidopsis.

    5. (10)

      This work uses pPCO1:GFP-GUS and pPCO2:GFP-GUS as reporters of hypoxia condition.

    6. Arabidopsis ethylene response reporter

      An and colleagues reveal that the protein levels of EIN3 increase in response to ethylene. This is the fundment of using EIN3-GFP to measure ethylene response in plants.

    7. Ethylene is produced by root tissues, and its level increases when roots are exposed to compacted soil

      Hussain and colleagues find that tomato plants with higher ethylene production have reduced growth in compacted soil when compared to tomato plants with lower ethylene production. This provides a connection between ethylene levels and plant growth in compacted soil.

    8. restricts diffusion of gases between roots

      This work reveals that air-filled porosity, bulk density, soil disturbance, the type of diffusion gases, and soil texture are factors that affects gas diffusion in soil.

    1. This approach has made it possible to microfabricate models of blood vessels (8, 9), muscles (10), bones (11), airways (12), liver (13–16), brain (17, 18), gut (19), and kidney (20, 21). However, it has not yet been possible to engineer integrated microsystems that replicate the complex physiological functionality of living organs by incorporating multiple tissues

      A big goal in biomedical science is to make artificial organs that can be used to save lives. However, generating these new organs as well as integrating them into a human body has remained challenging. The cited articles discuss how hard it is to make organs that accurately mimic their human counterparts. If scientists could fabricate functional tissues and organs with integrated blood vessels to sustain them, artificial organ transplants could become a major therapeutic tool!

    2. Although considerable advances have been made in the development of cell culture models as surrogates of tissues and organs for these types of studies (1), cultured cells commonly fail to maintain differentiation and expression of tissue-specific functions.

      Davilla et. al. discuss the advantages and disadvantages of lab-grown cell cultures that can mimic the function of kidneys and livers. While these cultures are inexpensive and can help measure drug-specific tissue interactions at a cellular/molecular level, the models do not accurately account for molecular transport and toxicity interactions between tissues and organs. This is because the cultures are grown on a flat surface, rather than in a 3D organ-like configuration. The authors conclude that cell culture models are a step towards pharmaceutical testing that does not use animal models, but further development is needed to effectively mimic the human body's reactions to various drugs.

    3. that are critical for the development and function of living organs

      In this review article by famous tissue engineer Donald Ingber, there is great discussion of all the factors that affect cellular growth and development. In particular, the mechanical forces of tension and compression (as we see in the lungs when we inhale and exhale) can play a very important role in how cells divide, grow, and communicate. 3D cell cultures and lung-on-a-chip technology offer the potential to mimic these mechanical forces that we observe in the body. This accounting for human-like biology in drug testing has the potential to make animal studies obsolete!

    1. Lst1-Sec23

      Lst1-Sec23 is a coat adaptor protein that carry the cargo molecules form ER to Golgi, which mainly to help the secretory proteins transportation.

    2. ER-phagy receptor Atg40

      Protein recycling and self-eating process that selectively happens in endoplasmic reticulum terms as ER-phagy (phagy means eating). Selective autophagy requires a receptor protein to recognize its degradation targets and directs the targets to be sequestrated by autophagosomes, a double membrane vesicle structure, which to be transported into lysosomes or vacuoles.

      A protein named as Atg40, has been recognized as a ER-phagy receptor protein in yeast. FAM134B is a putative mammals homologue of ATG40.

      Literature first explain the Atg40 ER-phagy receptor https://doi.org/10.1038/nature14506 (ATG40)

      https://doi.org/10.1038/nature14498 (FAM134B)

    3. we found an unexpected role for Lst1-Sec23 in ER-phagy that was independent from its function in secretion.

      Lst1-Sec23 is a coat adaptor protein that carry the cargo molecules form ER to Golgi, which mainly to help the secretory proteins transportation. The author discovered new function of the Lst1/Sec23 in self-eating and protein recycling process (autophagy), in which the Lst1-Sec23 functions together with the autophagy receptor, Atg40, to localize the ER domains for autophagic degradation.

    4. first ER-phagy receptors were identified

      First ER-phagy receptors that were identified in yeast is ATG40, and FAM134B in mammals.

    5. Lnp1 is an ER protein that resides at and stabilizes the three-way junctions that form when two tubules fuse to each other (23). In its absence, ER network rearrangements are disrupted and Atg40 puncta fail to access the autophagy machinery (17). As a consequence, ER is not packaged into autophagosomes in lnp1Δ cells

      Lnp1 is a protein to maintain the structure of ER by stabilizing rearrangements of the ER networks.

      Further reading: https://doi.org/10.1073/pnas.1805032115

  7. Dec 2022
    1. Imaging studies on mammalian cell lines (18–20), cardiac myotubes (21, 22), and syncytial human trophoblasts (23) have shown that apoptosis typically initiates at a single discrete focus or a small number of discrete foci and then spreads rapidly throughout the cell, and in some of these studies the propagation velocities appeared to be constant over distances of ~100 μm

      Scientists have clearly shown that apoptosis takes place in different cell types and beginning at specific points/positions, it spreads through apoptotic cells at a constant speed.

      This paper was able to demonstrate that the spreading of apoptosis through cells occurs via trigger waves.

    2. The powerful biochemical approaches provided by the Xenopus system have made Xenopus eggs and extracts useful model systems for the study of apoptosis

      Scientists have shown that the Xenopus egg extract is an effective medium for studying the process of apoptosis.

  8. Nov 2022
    1. During LMP, lysosomal intraluminal cathepsins and hydrolases leak into the cytosol, where they act as cell death proteases

      LMP results in the escape of protein-degrading proteins from the lysosomes to the cytoplasm, leading to initiation of cell death

    2. Additional sequence analyses revealed the presence of a conserved di-aspartyl sensor and an arginine latch, shown to be critical for the regulation of the calcium channel function of the bacterial (Bacillus subtilis) homolog BsYetJ and human GAAP (11, 12, 25).

      RECS1 has features (di-aspartyl sensor and an arginine latch) found in related proteins in bacteria and humans, which are well investigated.

    3. RECS1 and LFG are regarded as inhibitors of the extrinsic pathway of apoptosis as they block cell death induced by Fas ligand (18, 19), while BI-1, GRINA, and GAAP repress apoptosis induced by intracellular cytotoxic stimuli (10, 17).

      Here, RECS1 was reported to be an inhibitor (negative regulator) of apoptosis.

    4. In addition to BI-1, the TMBIM superfamily includes the following members: responsive to centrifugal force and shear stress 1 (RECS1/TMBIM1), lifeguard (LFG/TMBIM2), glutamate receptor ionotropic N-methyl-D-aspartate receptor 1 (GRINA/TMBIM3), Golgi anti-apoptotic protein (GAAP/TMBIM4), and growth hormone–inducible protein (GHITM/TMBIM5) (8).

      All these proteins negatively regulate programmed cell death

    5. There is a high degree of functional conservation in the mechanisms regulating cell death between vertebrates, with almost all the members of the BCL-2 and the TMBIM families conserved in zebrafish

      The functions of proteins in BCL-2 and the TMBIM family are similar across multiple organisms.

    6. BsYetJ has 27% identity with GAAP and 36% with RECS1 (fig. S7). In the bacterial BsYetJ, the closed channel conformation is maintained through the interaction of the Arg60 with a conserved di-aspartyl group formed by Asp171-Asp195, which are hydrogen-bonded to one another through their carboxylate groups

      The sequence and structure of the mammalian RECS1 is closely related to the bacteria BsYetJ

  9. May 2022
    1. recent claims that climate models overestimate the impact

      Some authors, like Sherwood Idso, argued that scientists were vastly overestimating global warming. These claims were based on simplified atmospheric models, which neglect important features of Earth's energy balance. In 2016, global warming was measured to be 1.00°C above the 20th century average, consistent with the conventional models.

    1. Several protocols for mixing based on chaotic flows have been proposed and demonstrated in macroscopic systems

      An earlier study presented a unified and systematic account of kinematics for mixing, blending, or stirring fluids. This work suggests that fluid mixing is the methodical stretching and folding of material lines and surfaces.

    2. Mixing of the fluid flowing through microchannels is important in a variety of applications: e.g., in the homogenization of solutions of reagents used in chemical reactions, and in the control of dispersion of material along the direction of

      Jones et al. proposed a method of controlling the spread of materials along the direction of flow as they are transported in a cylindrical pipe (Poiseuille flow).

    1. Osborn et al. (39)

      The authors made a multilayered electric dermis to provide tactile information to an amputee. The prosthesis and amputee demonstrate the ability to differentiate non-painful or painful stimuli using sensory feedback and a pain reflex feedback control system.

    2. Tee et al. (40) reported that the action potential of neurons was closely followed by the frequency of pulses.

      This group of researchers developed a skin-inspired mechanoreceptor, with output frequencies ranging between 0 and 200 hertz, which are pulses that mimic slow-adapting skin mechanoreceptors.

    1. humidity

      Shin et al, Lee et al, and Ma et al. have chosen to harness environmental humidity as the energy source for their robots. However, these robots have a limited speed of 6mm/s.

    2. crawling robots

      Rafsanjani et al. utilized Japanese paper folding techniques to create a soft robot mimicking the crawling motion of a snake. Similarly, Wang et al. employed inchworm movement patterns in their soft robots.

  10. Apr 2022
    1. (of cells)

      Many health and biotechnology research and assays depend on the efficient sorting of cells. Microfluidics allows for efficient and accurate cell sorting due to the ability to interact with cells using physical structures and processes occurring on the same scale. This is useful in drug development, disease detection, and cellular research.

    2. In a steady chaotic flow, the stretching and folding of volumes of the fluid proceed exponentially as a function of the axial distance traveled by the volume: Δr = lexp(−Δy/λ), where the initial transverse distance is taken to be l, and λ is a characteristic length determined by the geometry of trajectories in the chaotic flow

      Chaotic flow allows for faster mixing as it allows for the fluid components to stretch and fold much sooner along the flow direction. This allows to achieve full mixing within a much smaller channel length.

    3. analysis (of DNA and proteins)

      Microfluidics offers the potential for rapid and efficient analysis of DNA and proteins at a lower cost then traditional analysis. This is perhaps one of the most widely used commercial applications of microfluidics and has recently been seen most prominently in SARS-CoV-2 and other immunology testing tasks.

    1. An opposite trend exists for soft robots, as shown in the elliptical and blue color shaded area, which suggests that the relative speed increases as the body mass increases (19) except for recent robots driven by an external magnetic force (26–28).

      In soft robots, speed increases as body mass increases with the exception of robots using magnetic force actuation.

    1. Climatological cloud cover (50 percent) and aerosol properties (17) are used, with appropriate fractions of low (0.3), middle (0.1), and high (0.1) clouds.

      Toon and Pollack designed a model which gave global averages for the size distribution, chemical composition, and optical opaqueness of aerosols in the troposphere and stratosphere.

  11. Mar 2022
    1. magnetic force

      Prior studies conducted by Vogtmann et al, Hu et al, and Pierre et al. have embedded permanent magnets into the soft robot that allow for the generation of a magnetic field.

      This actuation method allows for faster movement, but the robot developed by Hu et al has a top speed (213 mm/s) that is still one-fourth of the robot presented in this work.

    2. relative speed may be more “ecologically relevant” than the absolute speed in various performance characterizations (61, 62)

      In their research, Damme and Van Dooren use computer simulations to investigate a mouse's chance to escape predation by varying speed and body size. The authors conclude that relative speed (body lengths per second) is a more "ecologically relevant trait" because it better predicts the prey's ability to escape predators. This notion opposes previously published research, which considered absolute speed (meters per second) as the main predictor for prey vulnerability.

    3. similar to many running animals (36)

      Dickinson et al found that most organisms (bi-pedal, multi-legged) use similar energy mechanisms for movement. In this article, our authors use piezoelectric material to mimic those movement patterns.

    4. Polyvinylidene difluoride (PVDF) is soft, flexible, and lightweight, making it suitable for potential soft robot applications (32, 33),

      Previous studies have utilized PVDF films for various soft robot applications to lower driving voltage, increase actuation motion and improve moving speed.

    1. To achieve a close-to-natural replacement, it is important to develop a tactile sensory system that perceives stimuli, encodes them into physiological responses, and then delivers them to the nerves or the brain to form sensory feedback (5, 

      Scientists, engineers, and clinicians need to work together to develop brain-computer interfaces (BCI) towards controlling artificial limbs with skill and speed approaching that of an able-bodied person.

    2. Saraf et al. (34) introduced a light-harvesting and self-powered monolith tactile sensor.

      The notable advancement in the article referenced here is the application of perovskite material within a monolithic tactile sensor. This material has properties of being ferroelectric and semiconducting which allows it to be made into a light harvesting, self-powered tactile sensor.

    3. Kim et al. (41) developed neuromorphic technology in neuroprosthetics.

      This paper draws inspiration from sensory (afferent) nerves to make flexible organic electronics. Afferent nerves carry sensations such as touch, pain, and temperature. The authors combined a pressure sensor, ring oscillator, and an ion gel-gated transistor to form an artificial mechanoreceptor. Their afferent nerve can detect movement, simultaneous pressure inputs, and distinguish braille characters.

    4. Miyamoto et al.

      This group fabricated inflammation-free, highly gas-permeable, ultrathin, lightweight and stretchable sensors that can be directly laminated onto human skin for long periods of time. Their unique device implemented nanomeshes, which aided in suppressing skin irritation and inflammation.

    5. Oddo et al. (38) reported an approach of intraneural stimulation that elicited discrimination of textural features by an artificial fingertip in intact and amputee humans.

      This publication describes a device that allows amputees to distinguish different textures using a sensorized artificial finger tip. This finger tip is unique because it includes a neuromorphic real-time mechano-neuro-transduction (MNT), a device that converts touch into nerve firing dynamics. These microsimulations are sent to an electrode, which is then directly attached to a nerve in a human subject. Both subjects with intact limbs and amputee subjects were able to distinguish differences in surface coarseness.

    1. chemical reactions

      Microfluidic chemical reactors offer advantages such as reduced chemical consumption, high surface-area-to-volume ratios, and improved safety that make them superior to macroscopic reaction settings. These have been implemented in fluorination, tumor drug delivery, and various other applications.

    2. The angular displacement, Δφm, is controlled by the geometry of the ridges

      The mixing efficiency (which is a function of angular displacement) can be optimized by changing the shape and the dimensions of the ridges.

    3. Furthermore, the experimentally observed dependence of the average rate of rotation,dΔφ/dy, on geometrical parameters (q, h, w, and θ) can be rationalized with a simple model

      Earlier studies have discovered how these two parameters effect each other. The authors developed a model to predict the effect of each geometrical parameter on the mixing efficiency.

    1. For example, the NASA Solar Maximum Mission is monitoring solar output with a relative accuracy of ~0.01 percent (57).

      Satellite measurements have greatly expanded the availability of precision measurements of solar luminosity and other external factors that determine climatic conditions on Earth.

    2. Preliminary experiments with sea ice models (56) suggest that all the sea ice may melt in summer, but part of it would refreeze in winter.

      A model of melting sea ice was constructed to account for heat flow in and out of ice, seasonal snow variations, and movement of ice packs. This model was used to predict the effects of a warming atmosphere on the Arctic Ocean.

    3. surface warming at high latitudes will be two to five times the global mean warming (52-55).

      Climatic conditions thousands of years ago have been studied extensively by combining geological evidence with computational climate models.

    4. An estimate can be obtained by comparing the predicted warming to the standard deviation, a, of the observed global temperature trend of the past century (50).

      Global temperature trends are affected by a large number of factors on short time scales. This variation from year to year can obscure long-term trends until they grow sufficiently large to rise above the noise. Statistical methods like these can be used to predict such trends and estimate when they will be clearly visible.

    5. Hoyt's rationale is that the penumbra, with a weaker magnetic field than the umbra, is destroyed more readily by an increase of convective flux from below.

      The structure of sunspots was correlated with temperature variations on Earth. This correlation was argued to be due to sunspots reducing the amount of radiation emitted by the Sun.

    6. showed that tropical tropospheric and stratospheric temperature changes computed with a one-dimensional climate model were of the same sign and order of magnitude as observed changes (45).

      The Mount Agung eruption provided an opportunity for researchers to collect data on stratospheric aerosols and compare the resulting climate effects with theoretical models. This work provided evidence for the viability of climate models for predicting atmospheric responses to large perturbations.

    7. Southern latitudes warmed ~0.4°C in the past century; results agree with a prior analysis for the late 1950's to middle 1970's (44).

      Early estimates of global cooling underrepresented climate trends in the Southern Hemisphere. Better data collection and analysis of data from stations south of the equator helped to correct these calculations.

    8. No major trend of O3 abundance has been observed, although it has been argued that continued increase of Freons will reduce O3 amounts (38).

      Chlorofluorocarbons (CFCs), previously used as refrigerants, were predicted to deplete stratospheric ozone by a series of rapid chain reactions. This effect was shown to be the primary cause of widespread ozone depletion, resulting in the adoption of the Montreal Protocol, which banned the use of CFCs globally in 1987.

    9. Trace gases that absorb in the infrared can warm the earth if their abundance increases (5, 34).

      Even chlorofluorocarbons, which are relatively low in abundance, have been estimated to have significant climate forcing effects.

    10. Ground albedo alterations associated with changing patterns of vegetation coverage have been suggested as a cause of global climate variations on time scales of decades to centuries (32).

      Global temperature changes due to human modification of the land were estimated. These modifications include the clearing of forests, construction of settlements, and expansion of deserts.

    11. Temporal variability of stratospheric aerosols due to volcanic eruptions appears to have been responsible for a large part of the observed climate change during the past century (27-30), as shown below.

      Simple models based only on variation of solar radiation and volcanic eruptions agree well with other estimates of preindustrial temperatures, indicating that these factors contribute strongly to overall climate variation in the absence of forcing by greenhouse gases.

    12. The warming calculated with the one-dimensional model for the CO2 increase from 1880 to 1980 (25) is 0.5°C if ocean heat capacity is neglected (Fig. 1).

      Historical global fuel consumption was used to estimate the amount of carbon dioxide in the atmosphere before reliable measurements were taken. This model estimates a concentration of 293 ppm in 1880.

    13. Delay of CO2 warming by the ocean can be illustrated with a "box diffusion" model (24), in which heat is stirred instantly through the mixed layer and diffused into the thermocline with diffusion coefficient k.

      Box diffusion models assume a well-mixed atmosphere and divide the ocean into surface and deep ocean boxes. Diffusion into the shallow ocean occurs much faster than diffusion into the deep ocean. These models outperform box models that only consider the ocean as a single reservoir.

    14. Pressure- and temperature-dependent absorption coefficients are from line-byline calculations for H2O, CO2, 03, N2O, and CH4 (15), including continuum H2O absorption (16).

      Careful measurements of the radiation absorbed by different atmospheric gases have greatly improved the accuracy of climate models.

    15. A one-dimensional radiative-convective (1-D RC) model (5, 13), which computes temperature as a function of altitude, can simulate planetary temperatures more realistically than the zerodimensional model of Eq. 1.

      Radiative-convective models assume that the atmosphere maintains a balance between heating (by the surface and by condensation of water) and cooling (by radiation into space).

  12. Feb 2022
    1. with the flight muscles and thorax of flying insects serving as an example in the higher frequency range (43).

      By studying asynchronous flight systems in flies, Dickinson and Tu concluded that the resonant properties of the thorax (the midsection of an insect) determine the contraction frequency of the muscles.

    2. light

      Light can be easily controlled with high resolution and light-based mechanisms have been used in order to avoid potentially invasive wires or electrodes, Wang et al. chooses to use light-driven hydrogel; Rogóz ̇ et al. utilizes liquid crystalline elastomers that change shape under light; Park et al. uses tissue engineering principles to engineer cells that respond to light cues. Still, these prior publications are unable to achieve speeds greater than 3.2 mm/s.

    3. Improving the mobility, efficiency, and robustness of soft robots made of a deformable body with the capability to carry extra weights to perform various functions has been challenging (1–4)

      Designing soft robots capable of carrying large weights has been challenging so far because of their lack of rigid structures.

    4. hopping robots

      In order to mimic a hop-like pattern, Kagawa et al. have used the movement style and foot path of cockroaches. On a larger scale, researchers like Haldane et al. have chosen a small primate, galagos, as their model animal which is known for having the highest vertical jumping ability.

    5. vertical movement of a cockroach (41)

      In this study, Full and Tu used a miniature force platform to measure the ground reaction forces of the American cockroach, Periplaneta americana. Using this method, the authors observed varying types of cockroach locomotion which they described as a bouncing gait, switching from quadrupedal and bipedal running.

    6. “robophysics”

      Aguilar et. al define "robophysics" as the pursuit of principles of self-generated motion.

    1. Park et al. (31) used a porous PDMS structure and achieved high sensitivity (1.5 kPa−1)

      This paper describes the first stretchable energy-harvesting electronic-skin device that is capable of differentiating and generating energy from pressure, bending, and vibration. The device had a maximum pressure sensitivity of 1.5 kPa-1, which is higher than the previously reported stretchable capacitive pressure sensors.

    2. Wang et al. (32) reported a sensor based on a silk microstructured surface that exhibited superior sensitivity (1.80 kPa−1) and a very low detectable pressure limit (0.6 Pa)

      This paper describes a flexible and transparent e-skin device that was achieved by combining silk-molded micro-patterned PDMS with single walled carbon nanotube ultra-thin films. This device has great pressure sensing performance, but it is a challenge to form large-scale and uniform e-skin with cost effective fabrication methods.

    3. There has been notable advancement in the field of designing prosthetic limbs integrated with rigid and/or flexible tactile sensors that are responsive to variable environments

      The notable advancement in the article referenced here is a stretchable prosthetic skin. The artificial skin made in this reference article had enhanced ability to sense stimuli in highly variable external environments. It also had the ability to sense skin moisture and temperature.

    1. transfers of small volumes (1 to 100 nl) of materials (5).

      A nonmechanical pumping mechanism was developed to move nano-liter and pico-liter sized drops of fluid within microchannels. The described system heats one end of a droplet and creates surface tension that causes a pressure difference in the channel, resulting in droplet motion.

    2. The group of Beebe has demonstrated chaotic stirring in a helical microchannel; in this design, stirring occurs as a result of eddies at the bends in the channel in flows of intermediateRe (i.e., Re > 1)

      A snake-like channel with repeating C-shaped segments was developed to enhance passive fluid mixing. This design achieved significantly more thorough mixing compared to straight channels and square-wave channels.

  13. Dec 2021
    1. are slowly declining (2, 28)

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

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

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

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

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

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

    3. the Antarctic ozone hole reached a record size

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

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

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

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

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

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

    5. both hemispheres (2)

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

    1. The most sophisticated models suggest a mean warming of 2° to 3.5°C for doubling of the CO2 concentration from 300 to 600 ppm (6-8).

      A complex computational model was constructed that considers geography, seasonal variation, and the circulation of heat and water across the entire globe. When the carbon dioxide concentration is increased quickly, the model predicts substantial heating of the Earth's surface.

    2. Increased atmospheric CO2 tends to close this window and cause outgoing radiation to emerge from higher, colder levels, thus warming the surface and lower atmosphere by the so-called greenhouse mechanism (5).

      Modeling of the effect of various manmade gases in the atmosphere showed that many pollutants absorb radiation that would otherwise be emitted to space. This causes energy to build up in the lower atmosphere, causing warming at the surface.

    3. Deforestation and changes in biosphere growth may also have contributed, but their net effect is probably limited in magnitude (2, 3).

      The interactions between the atmosphere, ocean, and land were modeled. These calculations showed that increased fossil fuel consumption was a much larger contributor to carbon dioxide levels than deforestation.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    2. (10–15)

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

    3. (7, 8)

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

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

    4. (3, 4)

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

    5. (1, 2)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    7. Roman sources from the fifth century BCE on

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    2. 22

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    4. additional costimulatory signals are necessary for T cell activation

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

  20. 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.

  21. 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

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

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

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

    2. exhibits severe growth retardation (17)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    2. We have developed and employed optogenetics technology

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

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

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

    1. [8 ± 1 R/Ra (SD)]

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

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

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

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

    2. 23

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

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

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

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

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

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

  23. 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.