•Fe rich pyrochlores of the type Bi2−xFe1+xSbO7 were prepared by solid state methods.•Structures determined using a combination of neutron and synchrotron X-ray diffraction.•Fe partially occupies the ...8-coordinate site.•Dispacive disorder of the Bi cations observed as a consequence of the 6s2 electrons.•Non-Vegard behaviour seen at low Fe contents due to disorder.
The structural and electronic properties of the series Bi2−xFe1+xSbO7 (0⩽x⩽0.6) were investigated using a combination of diffraction and spectroscopy. Synchrotron and neutron diffraction analysis show that Fe3+ cations substitute for Bi3+ onto the A site with increasing x, which was further confirmed by analysis of the Fe K/L-edge X-ray absorption near-edge spectra. The diffraction analysis indicated the presence of displacive disorder along the A2O chains, likely the result of the Bi3+ 6s2 lone pair, as well as non-Vegard-like behaviour of the lattice parameters in the Fe-poor region. Fe K-edge extended X-ray absorption fine-structure analysis of Bi2FeSbO7 confirmed the displacive disorder of the Bi3+ cations as well as Sb5+ and Fe3+ disorder on the B site.
The spike proteins that crown SARS‐CoV‐2, the novel coronavirus behind the nearly 2 million COVID‐19 deaths this year, may be the key to stopping the infectious disease firmly in its tracks. By ...recognizing and attaching to human cells, these spike proteins spearhead the process of SARS‐CoV‐2 infection in the body. Thus, understanding their architecture and mechanics is critical to pinpointing the vulnerabilities of this coronavirus and guiding therapeutic development. To that end, here we present a review of the latest discoveries in the spike proteins’ structure and function alongside a physical model of the spike protein, highlighting features of clinical interest in antibody, small‐molecule drug, and vaccine development.
The spike protein is comprised of two functional domains. The outer S1 domain includes the receptor binding domain, which recognizes and binds to an angiotensin‐converting enzyme 2 (ACE2) receptor on the surface of a lung, heart, kidney, or intestinal cell. Then, facilitated by the highly flexible inner S2 domain, the spike protein folds in on itself and fuses the viral envelope with the plasma membrane of the human cell. In doing so, the spike protein opens the doors for SARS‐CoV‐2 to release its viral genome inside the cell. Because spike proteins are glycoproteins, meaning their ectodomain is covered with sugar chains, the virus can evade the detection of the immune system and spread quickly throughout vital organs
The spike protein's position on the outer surface of SARS‐CoV‐2 and its critical role in the virus's function makes it one of the most promising targets for a coronavirus therapeutic. One novel approach to targeting spike proteins is the design of Anti‐S1 antibodies, which disarm the virus's ability to bind to the cell by attaching to the S1 subunit. The current challenge to antibody development is the flexibility of the S1 domain, which makes fusion highly effective. Further research is needed to stabilize the spike protein and maximize the efficacy of antibodies in inhibiting the virus's function. Another intriguing approach to coronavirus therapeutics is small‐molecule drug development. When linoleic acid (LA), an essential fatty acid molecule that maintains lung cell membranes, nestles into a newly discovered druggable pocket of the spike protein, the spike protein is locked into a less flexible, less infectious form. This new pocket is a putative binding site for even more potent small‐molecule inhibitors, which may be able to trap the spike protein in a completely non‐infectious form. With each new discovery surrounding the structure of the spike proteins at the heart of the COVID‐19 pandemic, we advance one step closer to developing novel therapeutics that trap SARS‐CoV‐2 in a virtually non‐infectious state.
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► Sperms in testes and spermathecae of the male and female stable flies were visualized using two fluorescent dyes. ► Adult stable flies were fed with reserpine-treated cattle blood ...to deplete biogenic amines. ► Reserpine treatment significantly reduced the rate of successful mating by males and oviposition by females. ► The amine-depleting effect of reserpine was confirmed by immunohistology of serotoninergic neurons innervating male testes.
Biogenic amines are known to play critical roles in key insect behaviors such as feeding and reproduction. This study documents the effects of reserpine on mating and egg-laying behaviors of the stable fly, Stomoxys calcitrans (L.) (Diptera: Muscidae), which is one of the most significant biting fly pests affecting cattle. Two sperm staining techniques were adapted successfully to reveal the morphology of stable fly sperm, for the first time, and determine successful mating in females through the assessment of sperm transfer. This approach was also applied to assess sperm transfer by males treated with different doses of reserpine. Mating or sperm transfer did not occur in flies during the first 3days after emergence. Thereafter, the percentage of females that mated increased with age. Reserpine treatment of males reduced sperm transfer in a dose-dependent manner. Older males were more sensitive to reserpine treatment than younger flies. Reserpine treatment of 5days old females reduced the number of eggs laid, but had no effect on egg-hatching rates. Results of immunoreactivity (IR) experiments indicated that serotonin in the neuronal processes innervating male testes was completely depleted by reserpine within 5h after treatment. This effect was transient as the serotonin immunoreactive signal was recovered in 33.3% of the males at 1day post-treatment and in 94.4% of the flies at 3days post-treatment. The results of this study concur with previous findings in other insect species and extend our knowledge of the critical roles biogenic amines play in mating and oviposition behaviors of the stable fly. The work could provide a foundation to further characterize the specific roles of individual biogenic amines and their receptors in stable fly reproduction.
Abstract
What public pressures do leaders face in international disputes? Leaders often denounce foreign actions as provocations, triggering public anger and demands for restitution. Rather than ...generating a reflexive rally around the flag, we argue that leaders who invoke foreign provocations—whether hypothetical, remembered, exaggerated, or real—face heightened public disapproval if they fail to take tough action in the present. Across two survey experiments and a quasi-experiment involving US naval patrols in the South China Sea, we find that incidents construed as provocative increase public pressure on the Chinese government to respond or incur public disapproval. We discuss possible explanations, how government elites seek to mitigate public disapproval, and how such events can change the logic of coercion and deterrence.
Long-term fumigation with pure phosphine at low-temperature injures lettuce and the injury is likely caused by a potential accumulation of CO2. In this study, iceberg and romaine lettuce were stored ...hermetically in fumigation chambers with and without absorbents for CO2 and ethylene for 3days at 2ºC as a simulation of long-term fumigation to determine the effects of the absorbents on accumulations of CO2 and ethylene and postharvest quality of lettuce. In the absence of absorbents, CO2 level increased from 0.08% at the start to 3.36% at the end of the 3-day hermetic storage. No accumulation of ethylene was detected. Hermetic storage resulted in significant CO2 injuries to both iceberg and romaine lettuce and quality degradation as compared with the controls at 14days after treatment. In the storage with absorbents, the CO2 level remained low throughout the storage and ethylene was undetectable, and the CO2 injury level was the same or lower than the control. Lettuce quality scores were either the same or better than lettuce in the control. Our findings suggest that the accumulation of CO2 alone caused injuries associated with long-term phosphine fumigation and CO2 absorbent has the potential to prevent such injuries.
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•Lettuce was subjected a 3-day hermetic storage at 2ºC as a simulation of low-temperature fumigation.•Hermetic storage resulted in a steady increase of CO2 level and injuries to lettuce.•The use of CO2 absorbent in hermetic storages effectively prevented injuries to lettuce.
The Olathe North MSOE Center for BioMolecular Modeling SMART Team used 3‐D modeling and printing technology to examine the structure‐function relationships and regulatory roles of ERβ. Estrogens are ...steroid hormones synthesized from cholesterol in cells of the ovary and other tissues expressing the enzyme aromatase. These hormones are secreted into the bloodstream and modulate numerous physiological functions through gene regulation. To achieve this, estrogens pass through cell and nuclear membranes, facilitated by their lipophilic and miniscule nature. In target cells, estrogens bind to nuclear transcription factors called estrogen receptors (ERs), the two primary types being estrogen receptor alpha (ERα) and beta (ERβ). ERs typically form either homodimers with an identical molecule or heterodimers of ERα with ERβ. Estrogen binding occurs at ER's ligand binding domain (LBD), activating the ER's DNA binding domain (DBD). The ER dimer then binds to DNA at estrogen response elements (EREs) located in the promoter regions of estrogen‐responsive genes, allowing the ER to regulate the transcription of target genes. However, this process is only one of four mechanisms by which ERs function. In addition to this genomic mechanism, ERs can also function through tethered, nongenomic, and ligand‐independent mechanisms. In all these processes, ERs' role as a gene regulator is determined by the physical change in the structure of various ER domains, making it essential to analyze the ERs' protein structure. In this review, we focus on the structure and function of ERβ because of its largely unexplored physiological significance and clinical potential. ERβ is most highly expressed in the ovaries, mammary glands, prostate, testes, gastrointestinal tract, and immune system. Transcriptional regulation by ERβ is essential for ovarian follicle maturation and ovulation. Additionally, ERβ is involved in neurogenesis, vascular function modulation, cardiac myocyte maintenance, and metabolism regulation, among other physiological functions. In a pathological context, recent studies suggest ERβ is tumor suppressing while ERα increases tumor growth. Specifically, ERβ can inhibit proliferation while inducing differentiation and apoptosis in tumor cells. Thus, activation of ERβ by synthetic agonists, known as selective estrogen receptor modulators (SERM), has clinical significance concerning the treatment of breast, prostate, colon, and ovarian cancers. Here, we present a review of the latest research on ERβ in conjunction with its physical model, emphasizing ERβ's regulatory roles in human health.
Support or Funding Information
This is a SMART Team project supported through the contributions of Dr. M.A. Karim Rumi of the University of Kansas Medical Center, the Milwaukee School of Engineering, and the Olathe Medical Professions 21st Century Academy.
This is from the Experimental Biology 2019 Meeting. There is no full text article associated with this published in The FASEB Journal.
Analog neuromorphic computing systems emulate the parallelism and connectivity of the human brain, promising greater expressivity and energy efficiency compared to those of digital systems. Though ...many devices have emerged as candidates for artificial neurons and artificial synapses, there have been few device candidates for artificial dendrites. In this work, we report on biocompatible graphene-based artificial dendrites (GrADs) that can implement dendritic processing. By using a dual side-gate configuration, current applied through a Nafion membrane can be used to control device conductance across a trilayer graphene channel, showing spatiotemporal responses of leaky recurrent, alpha, and Gaussian dendritic potentials. The devices can be variably connected to enable higher-order neuronal responses, and we show through data-driven spiking neural network simulations that spiking activity is reduced by ≤15% without accuracy loss while low-frequency operation is stabilized. This positions the GrADs as strong candidates for energy efficient bio-interfaced spiking neural networks.
Abstract only
Natural evolution and protein redesign have only explored a tiny fraction of theoretically possible protein structures. However,
de novo
protein design will prove powerful in ...engineering novel proteins with specific functions by comprehensively sampling the protein space using computational methods guided by protein folding principles.
De novo
protein design involves working backwards from a desired protein with special structure and function to derive an amino acid sequence capable of folding into such a conformation—a challenging approach due to the vast number of protein conformations to evaluate. Here, we present a review of the latest advancements in
de novo
protein design methods and applications in conjunction with a physical model of a
de novo
fluorescence‐activating β‐barrel protein. Approaches to
de novo
protein design include: (1) simulating the folding of a fixed amino acid sequence to determine each residue’s most stable conformation, (2) determining the amino acid sequence that folds into a desired protein conformation, and (3) performing comprehensive rapid evaluations of each possible conformation. This novel protein is then synthesized and validated through
in vitro
or
in vivo
assays. In one recent breakthrough by Baker et. al., a
de novo
approach was used to design a β‐barrel protein comprised of a cylindrical pleated β‐sheet which binds the fluorogenic compound DFHBI. This study is the first instance of a
de novo
protein designed to bind to a small molecule of interest, with applications in visualizing cell movement, gene expression, DNA replication, protein translation, and tumor progression. In designing this fluorescence activating β‐barrel protein, structural irregularities were introduced to stabilize the structure and enlarge the β‐barrel cavity. Subsequently, the optimal sequences for β‐barrels with reasonable binding site and affinity for DFHBI were designed by computationally adjusting individual residue conformations. Finally, this optimized protein was synthesized, which had greater affinity with DFHBI and increased fluorescence in
in vitro
and
in vivo
experiments.
Support or Funding Information
This is a SMART Team project supported through the contributions of Dr. Jinan Wang of the University of Kansas Center for Computational Biology, the Milwaukee School of Engineering, and the Olathe Medical Professions 21st Century Academy.
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