Structure of EPCR in a non-canonical conformation

Structural motion and conformational flexibility are often linked to biological functions of proteins. Whether the endothelial protein C receptor (EPCR), like other molecules, is vulnerable to folding transitions or might adopt alternative conformations remains unknown. The current understanding points to a rigid molecular structure suitable for binding of its ligands, like the anticoagulant protein C, or the CIDRα1 domains of Plasmodium falciparum. In this study, we have identified a novel conformation of EPCR, captured by X-ray diffraction analyses, whereby Tyr154 shows a dramatically altered structural arrangement, likely incompatible with protein C binding. Biolayer interferometry analysis confirms previous results supporting a critical role for this position in protein C binding. Importantly, the conformational change has no apparent effect in the bound lipid. We conclude these findings reveal a site of conformational vulnerability in EPCR and inform a highly malleable region that could modulate EPCR functions.

Developments of crystal structures and photoluminescence properties of Sr0.85Eu0.15Al12O19 green phosphors using different synthesis parameters

First, a solid-state reaction method was used to synthesize a [Formula: see text] phosphor at 1250[Formula: see text]C–1400[Formula: see text]C for 1 h, and its crystal structures and photoluminescence properties were investigated as a function of synthesis temperature. When the furnace reached the synthesis temperature, the 5% [Formula: see text] reduction atmosphere was infused and the reduction atmosphere was removed as the temperature was dropped to 800[Formula: see text]C. When 1200[Formula: see text]C was used as the synthesis temperature, the [Formula: see text], [Formula: see text], and [Formula: see text] phases co-existed; only one weak emission peak was observed in the photoluminescence excitation (PLE) spectra, and two weak emission peaks were observed in the photoluminescence emission (PL) spectra. When the [Formula: see text] phosphors were synthesized at a temperature higher than 1200[Formula: see text]C, the diffraction intensities of [Formula: see text], [Formula: see text], and [Formula: see text] phases were almost unchanged, but the crystal sizes of [Formula: see text] powders increased. For [Formula: see text] phosphors, PLE spectra had one broad exciting band with two centered wavelengths of 317 and 365 nm, and PL spectra had one emission band with one centered wavelength of 513 nm. As the synthesis temperature rose, the emission intensities of PLE and PL spectra increased. Second, we show that the removed temperature of reduction atmosphere of [Formula: see text] phosphors had an apparent effect on their emission properties of PLE and PL spectra.

Paracrine FGFs target skeletal muscle to exert potent anti-hyperglycemic effects

Several members of the FGF family have been identified as potential regulators of glucose homeostasis. We previously reported that a low threshold of FGF-induced FGF receptor 1c (FGFR1c) dimerization and activity is sufficient to evoke a glucose lowering activity. We therefore reasoned that ligand identity may not matter, and that besides paracrine FGF1 and endocrine FGF21, other cognate paracrine FGFs of FGFR1c might possess such activity. Indeed, via a side-by-side testing of multiple cognate FGFs of FGFR1c in diabetic mice we identified the paracrine FGF4 as a potent anti-hyperglycemic FGF. Importantly, we found that like FGF1, the paracrine FGF4 is also more efficacious than endocrine FGF21 in lowering blood glucose. We show that paracrine FGF4 and FGF1 exert their superior glycemic control by targeting skeletal muscle, which expresses copious FGFR1c but lacks β-klotho (KLB), an obligatory FGF21 co-receptor. Mechanistically, both FGF4 and FGF1 upregulate GLUT4 cell surface abundance in skeletal muscle in an AMPKα-dependent but insulin-independent manner. Chronic treatment with rFGF4 improves insulin resistance and suppresses adipose macrophage infiltration and inflammation. Notably, unlike FGF1 (a pan-FGFR ligand), FGF4, which has more restricted FGFR1c binding specificity, has no apparent effect on food intake. The potent anti-hyperglycemic and anti-inflammatory properties of FGF4 testify to its promising potential for use in the treatment of T2D and related metabolic disorders.

No Strong Evidence of Stereotype Threat in Females: A Reassessment of the Meta-Analysis

Recently, Picho-Kiroga (2021) published a meta-analysis on the effect of stereotype threat on females. Their conclusion was that the average effect size for stereotype threat studies was d = .28, but that effects are overstated because the majority of studies on stereotype threat in females include methodological characteristics that inflate the apparent effect size. In this response, I show that Picho-Kiroga et al. (2021) committed fundamental errors in their meta-analysis that undermine confidence in the article and warrant major corrections. But even if the data were not flawed, the conclusion that Picho-Kiroga et al. (2021) should have reached is that their results are most consistent with a population effect size of zero. There is no compelling evidence that stereotype threat is a real phenomenon in females.

The Activity of Native Vacuolar Proton-ATPase in an Oscillating Electric Field – Demystifying an Apparent Effect of Music on a Biomolecule

The effect of an oscillating electric field generated from music on yeast vacuolar proton-ATPase (V-ATPase) activity in its native environment is reported. An oscillating electric field is generated by electrodes that are immersed into a dispersion of yeast vacuolar membrane vesicles natively hosting a high concentration of active V-ATPase. The substantial difference in the ATP hydrolysing activity of V-ATPase under the most stimulating and inhibiting music is unprecedented. Since the topic, i.e., an effect of music on biomolecules, is very attractive for non-scientific, esoteric mystification, we provide a rational explanation for the observed new phenomenon. Good correlation is found between changes in the specific activity of the enzyme and the combined intensity of certain frequency bands of the Fourier spectra of the music clips. Most prominent identified frequencies are harmonically related to each other and to the estimated rotation rate of the enzyme. These results lead to the conclusion that the oscillating electric field interferes with periodic trans-membrane charge motions in the working enzyme.

'Bearly' Changing with the Seasons: Bears of Five Species Show Few Behavioral Changes Across Seasons and at Varying Visitor Densities

In natural environments, bear behavior follows seasonal patterns but the zoo environment differs from the natural environment in several ways, including the presence of zoo visitors. Although typically difficult to disentangle, we were able to tease apart the effects of seasonal changes and visitor density on the visibility and behavior of 10 bears representing five species housed at Cleveland Metroparks Zoo due to the disruption caused by COVID-19. We conducted a longitudinal bear behavior monitoring project from June, 2017-November, 2020. Bears were more visible in the spring and in the presence of visitors, locomoted more and were less inactive when large crowds were present, foraged and locomoted more when it was earlier in the day, and locomoted more at higher temperatures. There were limited differences in bear visibility to observers between 2020 (when the zoo was temporarily closed to visitors) and the previous three years. There were no differences in rates of stereotypy or social behavior across seasons, crowds, or daily attendance categories. Based on these limited differences, neither season nor visitor density seemed to have an apparent effect on bear behavior or welfare.

A CENH3 mutation promotes meiotic exit and restores fertility in SMG7-deficient Arabidopsis

Meiosis in angiosperm plants is followed by mitotic divisions to form multicellular haploid gametophytes. Termination of meiosis and transition to gametophytic development is, in Arabidopsis, governed by a dedicated mechanism that involves SMG7 and TDM1 proteins. Mutants carrying the smg7-6 allele are semi-fertile due to reduced pollen production. We found that instead of forming tetrads, smg7-6 pollen mother cells undergo multiple rounds of chromosome condensation and spindle assembly at the end of meiosis, resembling aberrant attempts to undergo additional meiotic divisions. A suppressor screen uncovered a mutation in centromeric histone H3 (CENH3) that increased fertility and promoted meiotic exit in smg7-6 plants. The mutation led to inefficient splicing of the CENH3 mRNA and a substantial decrease of CENH3, resulting in smaller centromeres. The reduced level of CENH3 delayed formation of the mitotic spindle but did not have an apparent effect on plant growth and development. We suggest that impaired spindle re-assembly at the end of meiosis limits aberrant divisions in smg7-6 plants and promotes formation of tetrads and viable pollen. Furthermore, the mutant with reduced level of CENH3 was very inefficient haploid inducer indicating that differences in centromere size is not the key determinant of centromere-mediated genome elimination.

The 3'UTR of the orb2 gene encoding the Drosophila CPEB translation factor plays a critical role in spermatogenesis

CPEB proteins are conserved translation regulators involved in multiple biological processes. One of these proteins in Drosophila, Orb2, is a principal player in spermatogenesis. It is required for meiosis and spermatid differentiation. During the later process orb2 mRNAs and proteins are localized within the developing spermatid. To evaluate the role of orb2 mRNA 3'UTR in spermatogenesis, we used the CRISPR/Cas9 system to generate a deletion of the orb2 3'UTR, orb2R. This deletion disrupts the process of spermatid differentiation but has no apparent effect on meiosis. Differentiation abnormalities include defects in the initial polarization of the 64-cell spermatid cysts, mislocalization of mRNAs and proteins in the elongating spermatid tails, altered morphology of the elongating spermatid tails, and defects in the assembly of the individualization complex. These disruptions in differentiation appear to arise because orb2 mRNAs and proteins are not properly localized within the 64-cell spermatid cyst.

Fallopian tube anatomy predicts pregnancy and pregnancy outcomes after tubal reversal surgery

We conducted this study to determine whether fallopian tube anatomy can predict the likelihood of pregnancy and pregnancy outcomes after tubal sterilization reversal. We built a flexible, non-parametric, multivariate model via generalized additive models to assess the effects of the following tubal parameters observed during tubal reparative surgery: tubal lengths; differences in tubal segment location and diameters at the anastomosis sites; and fibrosis of the tubal muscularis. In this study, population, age, and tubal length—in that order—were the primary factors predicting the likelihood of pregnancy. For pregnancy outcomes, tubal length was the most influential predictor of birth and ectopic pregnancy, while age was the primary predictor of miscarriage. Segment location and diameters contributed slightly to the odds of miscarriage and ectopic pregnancy. Tubal muscularis fibrosis had little apparent effect. This study is the first to show that a statistical learning predictive model based on fallopian tube anatomy can predict pregnancy and pregnancy outcome probabilities after tubal reversal surgery.