A Structural Understanding of Class B GPCR Selectivity and Activation Revealed

Ma et al. (2020) and Liang et al. (2020) describe the cryo-EM structures of three class B G protein-coupled receptors (GPCRs) in complex with native peptides and Gs. Their work establishes the structural basis of peptide specificity and a conserved mechanism of receptor activation and G protein coupling for class B GPCRs. Ma et al. (2020) and Liang et al. (2020) describe the cryo-EM structures of three class B G protein-coupled receptors (GPCRs) in complex with native peptides and Gs. Their work establishes the structural basis of peptide specificity and a conserved mechanism of receptor activation and G protein coupling for class B GPCRs

Activation mechanisms for a universal signalling protein news-and-views

Computational and biochemical studies have revealed the mechanisms by which arrestin proteins are activated by G-protein-coupled receptors - potentially opening up broad avenues for drug discovery

A self-activating orphan receptor

[No abstract available

The HI content of Early-Type Galaxies from the ALFALFA survey I. Catalogued HI sources in the Virgo cluster

Aims: We are using the Arecibo Legacy Fast ALFA survey (ALFALFA), which is covering 17% of the sky at 21 cm, to study the HI content of Early-Type galaxies (ETG) in an unbiased way. The aim is to get an overall picture of the hot, warm and cold ISM of ETG, as a function of galaxy mass and environment, to understand its origin and fate, and to relate it to the formation and evolution history of these objects. Methods: This paper deals with the first part of our study, which is devoted to the 8-16 deg. declination strip in the Virgo cluster. In this sky region, using the Virgo Cluster Catalogue (VCC), we have defined an optical sample of 939 ETG, 457 of which are brighter than the VCC completeness limit at B_T=18.0. We have correlated this optical sample with the catalogue of detected HI sources from ALFALFA. Results: Out of the 389 ETG from the VCC with B_T<=18.0, outside the 1 deg. region of poor HI detection around M87, and corrected for background contamination of VCC galaxies without a known radial velocity, only 9 galaxies (2.3%) are detected in HI with a completeness limit of 3.5 and 7.6 x 10^7 Mo of HI for dwarf and giant ETG, respectively. In addition 4 VCC ETG with fainter magnitudes are also detected. Our HI detection rate is lower than previously claimed. The majority of the detected ETG appear to have peculiar morphology and to be located near the edges of the Virgo cluster. Conclusions: Our preliminary conclusion is that cluster ETG contain very little neutral gas, with the exceptions of a few peculiar dwarf galaxies at the edge of the ETG classification and of very few larger ETG, where the cold gas could have a recent external origin.Comment: Accepted for publication in Astronomy and Astrophysics; 6 pages, 3 figure

Gambogic Acid, a Natural Product Inhibitor of Hsp90

A high-throughput screening of natural product libraries identified (−)-gambogic acid (1), a component of the exudate of Garcinia harburyi, as a potential Hsp90 inhibitor, in addition to the known Hsp90 inhibitor celastrol (2). Subsequent testing established that 1 inhibited cell proliferation, brought about the degradation of Hsp90 client proteins in cultured cells, and induced the expression of Hsp70 and Hsp90, which are hallmarks of Hsp90 inhibition. Gambogic acid also disrupted the interaction of Hsp90, Hsp70, and Cdc37 with the heme-regulated eIF2α kinase (HRI, an Hsp90-dependent client) and blocked the maturation of HRI in vitro. Surface plasmon resonance spectroscopy indicated that 1 bound to the N-terminal domain of Hsp90 with a low micromolar Kd, in a manner that was not competitive with the Hsp90 inhibitor geldanamycin (3). Molecular docking experiments supported the posit that 1 binds Hsp90 at a site distinct from Hsp90s ATP binding pocket. The data obtained have firmly established 1 as a novel Hsp90 inhibitor and have provided evidence of a new site that can be targeted for the development of improved Hsp90 inhibitors

Characterization of Western Corn Rootworm (Coleoptera: Chrysomelidae) susceptibility to foliar insecticides in northeast Nebraska

Foliar-applied insecticides are commonly used for adult Western Corn Rootworm (WCR), Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), control in Nebraska but little efficacy data is available. Anecdotal reports of reduced efficacy in areas of northeast Nebraska led to the conduct of this study. Objectives were to (i) evaluate the efficacy of commercial applications of commonly used formulated insecticides (bifenthrin, lambda-cyhalothrin, chlorpyrifos, or tank mixes) for WCR control in 7 northeast Nebraska counties during 2019 and 2020 and (ii) conduct adult WCR concentration-response vial bioassays with bifenthrin, chlorpyrifos, and dimethoate active ingredients on a subset of field populations. Whole plant counts (WPC) were used to measure WCR densities in insecticide-treated and untreated maize fields before and after insecticide application. Field control was excellent with organophosphate/pyrethroid tank mixes as proportional change in mean WPC of treated fields was significantly reduced (\u3e0.90) versus untreated fields where little change in WPC occurred. The exception was one treated Boone County field where proportional reduction in WPC was ≤0.78. Bioassays revealed LC50s and resistance ratios of most populations exposed to bifenthrin and dimethoate were not significantly different than the susceptible control. Most populations exhibited a low level of chlorpyrifos resistance when compared to the susceptible control. Field and lab data suggest the local onset of practical WCR field-evolved resistance to bifenthrin in Boone County and chlorpyrifos in Boone and Colfax counties. Results of this study will increase our understanding of WCR resistance evolution, serve as a comprehensive baseline for future research, and inform WCR management programs

Women at Altitude: Sex-Related Physiological Responses to Exercise in Hypoxia.

Sex differences in physiological responses to various stressors, including exercise, have been well documented. However, the specific impact of these differences on exposure to hypoxia, both at rest and during exercise, has remained underexplored. Many studies on the physiological responses to hypoxia have either excluded women or included only a limited number without analyzing sex-related differences. To address this gap, this comprehensive review conducted an extensive literature search to examine changes in physiological functions related to oxygen transport and consumption in hypoxic conditions. The review encompasses various aspects, including ventilatory responses, cardiovascular adjustments, hematological alterations, muscle metabolism shifts, and autonomic function modifications. Furthermore, it delves into the influence of sex hormones, which evolve throughout life, encompassing considerations related to the menstrual cycle and menopause. Among these physiological functions, the ventilatory response to exercise emerges as one of the most sex-sensitive factors that may modify reactions to hypoxia. While no significant sex-based differences were observed in cardiac hemodynamic changes during hypoxia, there is evidence of greater vascular reactivity in women, particularly at rest or when combined with exercise. Consequently, a diffusive mechanism appears to be implicated in sex-related variations in responses to hypoxia. Despite well-established sex disparities in hematological parameters, both acute and chronic hematological responses to hypoxia do not seem to differ significantly between sexes. However, it is important to note that these responses are sensitive to fluctuations in sex hormones, and further investigation is needed to elucidate the impact of the menstrual cycle and menopause on physiological responses to hypoxia

Cross validation of bi-modal health-related stress assessment

This study explores the feasibility of objective and ubiquitous stress assessment. 25 post-traumatic stress disorder patients participated in a controlled storytelling (ST) study and an ecologically valid reliving (RL) study. The two studies were meant to represent an early and a late therapy session, and each consisted of a "happy" and a "stress triggering" part. Two instruments were chosen to assess the stress level of the patients at various point in time during therapy: (i) speech, used as an objective and ubiquitous stress indicator and (ii) the subjective unit of distress (SUD), a clinically validated Likert scale. In total, 13 statistical parameters were derived from each of five speech features: amplitude, zero-crossings, power, high-frequency power, and pitch. To model the emotional state of the patients, 28 parameters were selected from this set by means of a linear regression model and, subsequently, compressed into 11 principal components. The SUD and speech model were cross-validated, using 3 machine learning algorithms. Between 90% (2 SUD levels) and 39% (10 SUD levels) correct classification was achieved. The two sessions could be discriminated in 89% (for ST) and 77% (for RL) of the cases. This report fills a gap between laboratory and clinical studies, and its results emphasize the usefulness of Computer Aided Diagnostics (CAD) for mental health care

Методы измерения фазового сдвига с промежуточным преобразованием напряжение-частота

В статті розглянуті методи вимірювання фазового зсуву з проміжним перетворенням напруга-частота. Проаналізовано переваги й недоліки методів. Проведено оцінку похибки, обумовленої неточністю формування часових інтервалів.In article methods of measurement of phase shift with preliminary transformation a voltage-frequency are considered. Their merits and demerits are analyzed. The estimation of the error caused by discrepancy of formation of time intervals is made