166 research outputs found
Comparison Between Standard HABIT and HABIT-VR: Hand-Arm Function and Patient Acceptability Differencesâ
https://digitalcommons.unmc.edu/surp2022/1002/thumbnail.jp
Pnictogens Allotropy and Phase Transformation during van der Waals Growth
Pnictogens have multiple allotropic forms resulting from their ns2 np3
valence electronic configuration, making them the only elemental materials to
crystallize in layered van der Waals (vdW) and quasi-vdW structures throughout
the group. Light group VA elements are found in the layered orthorhombic A17
phase such as black phosphorus, and can transition to the layered rhombohedral
A7 phase at high pressure. On the other hand, bulk heavier elements are only
stable in the A7 phase. Herein, we demonstrate that these two phases not only
co-exist during the vdW growth of antimony on weakly interacting surfaces, but
also undertake a spontaneous transformation from the A17 phase to the
thermodynamically stable A7 phase. This metastability of the A17 phase is
revealed by real-time studies unraveling its thickness-driven transition to the
A7 phase and the concomitant evolution of its electronic properties. At a
critical thickness of ~4 nm, A17 antimony undergoes a diffusionless shuffle
transition from AB to AA stacked alpha-antimonene followed by a gradual
relaxation to the A7 bulk-like phase. Furthermore, the electronic structure of
this intermediate phase is found to be determined by surface self-passivation
and the associated competition between A7- and A17-like bonding in the bulk.
These results highlight the critical role of the atomic structure and
interfacial interactions in shaping the stability and electronic
characteristics of vdW layered materials, thus enabling a new degree of freedom
to engineer their properties using scalable processes
On the Importance of Electroweak Corrections for Majorana Dark Matter Indirect Detection
Recent analyses have shown that the inclusion of electroweak corrections can
alter significantly the energy spectra of Standard Model particles originated
from dark matter annihilations. We investigate the important situation where
the radiation of electroweak gauge bosons has a substantial influence: a
Majorana dark matter particle annihilating into two light fermions. This
process is in p-wave and hence suppressed by the small value of the relative
velocity of the annihilating particles. The inclusion of electroweak radiation
eludes this suppression and opens up a potentially sizeable s-wave contribution
to the annihilation cross section. We study this effect in detail and explore
its impact on the fluxes of stable particles resulting from the dark matter
annihilations, which are relevant for dark matter indirect searches. We also
discuss the effective field theory approach, pointing out that the opening of
the s-wave is missed at the level of dimension-six operators and only encoded
by higher orders.Comment: 25 pages, 6 figures. Minor corrections to match version published in
JCA
Roadmap for the use of base editors to decipher drug mechanism of action
CRISPR base editors are powerful tools for large-scale mutagenesis studies. This kind of approach can elucidate the mechanism of action of compounds, a key process in drug discovery. Here, we explore the utility of base editors in an early drug discovery context focusing on G-protein coupled receptors. A pooled mutagenesis screening framework was set up based on a modified version of the CRISPR-X base editor system. We determine optimized experimental conditions for mutagenesis where sgRNAs are delivered by cell transfection or viral infection over extended time periods (>14 days), resulting in high mutagenesis produced in a short region located at -4/+8 nucleotides with respect to the sgRNA match. The ÎČ2 Adrenergic Receptor (B2AR) was targeted in this way employing a 6xCRE-mCherry reporter system to monitor its response to isoproterenol. The results of our screening indicate that residue 184 of B2AR is crucial for its activation. Based on our experience, we outline the crucial points to consider when designing and performing CRISPR-based pooled mutagenesis screening, including the typical technical hurdles encountered when studying compound pharmacolog
Structure and Function of Human Erythrocyte Pyruvate Kinase MOLECULAR BASIS OF NONSPHEROCYTIC HEMOLYTIC ANEMIA
Deficiency of human erythrocyte isozyme (RPK) is, together with glucose-6-phosphate dehydrogenase deficiency, the most common cause of the nonspherocytic hemolytic anemia. To provide a molecular framework to the disease, we have solved the 2.7 A resolution crystal structure of human RPK in complex with fructose 1,6-bisphosphate, the allosteric activator, and phosphoglycolate, a substrate analogue, and we have functionally and structurally characterized eight mutants (G332S, G364D, T384M, D390N, R479H, R486W, R504L, and R532W) found in RPK-deficient patients. The mutations target distinct regions of RPK structure, including domain interfaces and catalytic and allosteric sites. The mutations affect to a different extent thermostability, catalytic efficiency, and regulatory properties. These studies are the first to correlate the clinical symptoms with the molecular properties of the mutant enzymes. Mutations greatly impairing thermostability and/or activity are associated with severe anemia. Some mutant proteins exhibit moderate changes in the kinetic parameters, which are sufficient to cause mild to severe anemia, underlining the crucial role of RPK for erythrocyte metabolism. Prediction of the effects of mutations is difficult because there is no relation between the nature and location of the replaced amino acid and the type of molecular perturbation. Characterization of mutant proteins may serve as a valuable tool to assist with diagnosis and genetic counseling
Effect of a Low-Moderate Exercise Program on Dysmetabolism in Older Adults: Results of a Randomized Controlled Trial
Physical exercise has been shown to improve dysmetabolism in older adults, reducing cardiovascular risk, while its role in preventing dysmetabolism is less known. Moreover, most of the trials use exercise programs that are difficult to put into daily practice. The purpose of this Randomized Controlled Trial (RCT) was to evaluate the effectiveness of a 3-month moderate exercise program in improving or preventing dysmetabolism in 120 older adults, randomly selected for the exercise program (experimental group) or cultural activities (control group). None of the subjects were following a hypocaloric diet, and all of them reported healthy eating habits. Anthropometric (Body Mass Index (BMI) and Waist Circumference (WC)) and metabolic variables (fasting plasma glucose (FPG), High-Density Lipoprotein Cholesterol (HDL-C), and triglycerides (TG)) were assessed at baseline (T0) and at the end of the trial (T1). Dysmetabolism was defined by the presence of an increased WC plus at least two metabolic alterations. At T0, the two groups did not differ by sex, age, education, BMI, WC, FPG, HDL-C levels, and prevalence of dysmetabolism. The mean BMI value indicated overweight, and WC values were higher than the cut-off. At T1, a slight reduction in the number of people with dysmetabolism was found only in the experimental group. However, none of the individuals without dysmetabolism at T0 in the experimental group developed it at T1, while 11.4% developed it in the control group (p = 0.032). This study highlights that a moderate exercise program, accessible in daily practice, can prevent dysmetabolism in older adults, even while being overweight, while if dysmetabolism is already present, more prolonged combined nutritional and exercise interventions will be needed
Heterogeneity of Early Host Response to Infection with Four Low-Pathogenic H7 Viruses with a Different Evolutionary History in the Field
Once low-pathogenic avian influenza viruses (LPAIVs) of the H5 and H7 subtypes from wild birds enter into poultry species, there is the possibility of them mutating into highly pathogenic avian influenza viruses (HPAIVs), resulting in severe epizootics with up to 100% mortality. This mutation from a LPAIV to HPAIV strain is the main cause of an AIV's major economic impact on poultry production. Although AIVs are inextricably linked to their hosts in their evolutionary history, the contribution of host-related factors in the emergence of HPAI viruses has only been marginally explored so far. In this study, transcriptomic sequencing of tracheal tissue from chickens infected with four distinct LP H7 viruses, characterized by a different history of pathogenicity evolution in the field, was implemented. Despite the inoculation of a normalized infectious dose of viruses belonging to the same subtype (H7) and pathotype (LPAI), the use of animals of the same age, sex and species as well as the identification of a comparable viral load in the target samples, the analyses revealed a heterogeneity in the gene expression profile in response to infection with each of the H7 viruses administered
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