Miracle-dz/UniFAR-FTUs huggingface dataset:
Computational prediction and experimental validation of Salmonella Typhimurium SopE-mediated fine-tuning of autophagy in intestinal epithelial cells

Macroautophagy is a ubiquitous homeostasis and health-promoting recycling process of eukaryotic cells, targeting misfolded proteins, damaged organelles and intracellular infectious agents. Some intracellular pathogens such as Salmonella enterica serovar Typhimurium hijack this process during pathogenesis. Here we investigate potential protein-protein interactions between host transcription factors and secreted effector proteins of Salmonella and their effect on host gene transcription. A systems-level analysis identified Salmonella effector proteins that had the potential to affect core autophagy gene regulation. The effect of a SPI-1 effector protein, SopE, that was predicted to interact with regulatory proteins of the autophagy process, was investigated to validate our approach. We then confirmed experimentally that SopE can directly bind to SP1, a host transcription factor, which modulates the expression of the autophagy gene MAP1LC3B. We also revealed that SopE might have a double role in the modulation of autophagy: Following initial increase of MAP1LC3B transcription triggered by Salmonella infection, subsequent decrease in MAP1LC3B transcription at 6h post-infection was SopE-dependent. SopE also played a role in modulation of the autophagy flux machinery, in particular MAP1LC3B and p62 autophagy proteins, depending on the level of autophagy already taking place. Upon typical infection of epithelial cells, the autophagic flux is increased. However, when autophagy was chemically induced prior to infection, SopE dampened the autophagic flux. The same was also observed when most of the intracellular Salmonella cells were not associated with the SCV (strain lacking sifA) regardless of the autophagy induction status before infection. We demonstrated how regulatory network analysis can be used to better characterise the impact of pathogenic effector proteins, in this case, Salmonella. This study complements previous work in which we had demonstrated that specific pathogen effectors can affect the autophagy process through direct interaction with autophagy proteins. Here we show that effector proteins can also influence the upstream regulation of the process. Such interdisciplinary studies can increase our understanding of the infection process and point out targets important in intestinal epithelial cell defense.
The effects of genetic distance, nutrient conditions, and recognition ways on outcomes of kin recognition in Glechoma longituba

Kin recognition might help plants decrease competitive cost and improve inclusive fitness with close genes; thus it might interact with environmental factors to affect communities. Whether and how various factors, such as the genetic distance of neighbors, environmental stressors, or the way a plant recognizes its neighbors, might modify plant growth strategies remains unclear. To answer these questions, we conducted experiments in which ramets of a clonal plant, Glechoma longituba, were grown adjacent to different genetically related neighbors (clone kin / close kin / distant kin) in different nutrient conditions (high / medium / low), or with only root exudates from pre-treatment in culture solution. By comparing competitive traits, we found that: (1) kin recognition in G. longituba was enhanced with closer genetic distance; (2) the outcomes of kin recognition were influenced by the extent of nutrient shortage; (3) kin recognition helped to alleviate the nutrient shortage effect; (4) kin recognition via root exudates affected only below-ground growth. Our results provide new insights on the potential for manipulating the outcome of kin recognition by altering neighbor genetic distance, nutrient conditions and recognition ways. Moreover, kin recognition can help plants mitigate the effects of nutrient shortage, with potential implications in agricultural research.
Highly sensitive refractive index sensor based on hybrid plasmonic waveguide microring resonator

A refractive index (RI) sensor based on straight silicon strip waveguide and a hybrid plasmonic microring resonator is presented. The hybrid waveguide is made up of a Metal-Air-Silicon structure, where the electric field is significantly enhanced in the narrow air gap. The transmission spectrum and electric field distribution of this sensor structure are simulated using Finite Element Method (FEM). Due to a large overlap of the optical field in the hybrid microring resonator and the sensing medium, this sensor can be used for both gas and bio sensing applications. The best sensitivity of 690 nm/RIU and 401 nm/RIU is obtained for gas and bio sensing, respectively. The obtained values are relatively high as compared to conventional dielectric microring resonator sensors. Our proposed sensor design has a potential to find further applications in biomedical science and nanophotonic circuits.
Forced changes in El Niño–Southern Oscillation due to global warming and the associated uncertainties in ACCESS-ESM1.5 large ensembles

Understanding the forced response of El Niño–Southern Oscillation (ENSO) to future global warming (GW) is important for reliable climate projections; however, many important aspects of this response are yet to be fully understood. Here, we use two large ensembles of CMIP6 historical and SSP3-7.0 experiments (each with 40 ensemble members), performed with ACCESS-ESM1.5, to investigate the combined greenhouse gas (GHG) and aerosol forced changes in selected ENSO properties. We document the forced changes in ENSO's amplitude, power spectrum, skewness, and feedbacks and quantify the internal variability associated with these forced changes. There is a modest but statistically significant GW-induced increase in the ensemble-mean ENSO amplitude and a sizable ensemble variation (due to internal variability) with both increases (in 80% of the members) and decreases. To understand the mechanism of this variation, we examine the role of changes in the mean state and atmosphere-ocean coupling processes in the Pacific. We find that the ensemble variation of GW-induced ENSO amplitude change is most sensitive to the zonal wind forcing change. A change in the zonal gradient of mean sea surface temperatures (SSTs) also plays an important role in the ENSO amplitude change, with the changes in the atmospheric Bjerknes feedback and thermocline feedback playing a minor role. The implications and some caveats of these findings are discussed.
Evaluation of commonly used cardiovascular drugs in inhibiting vonoprazan metabolism in vitro and in vivo

As a novel acid-suppressing drug, vonoprazan shows the potential to replace traditional proton-pump inhibitors. With its widespread use, some adverse effects that require further study have emerged due to drug–drug interactions. Our study is the first experiment that evaluated the drug–drug interactions of eleven common cardiovascular drugs that inhibit vonoprazan metabolism in vitro and in vivo. Rat liver microsome incubation and molecular simulation docking were applied to explore the inhibition mechanism. Amlodipine and nifedipine showed inhibitory effects on vonoprazan metabolism in both rat and human liver microsomes in the first evaluation part in vitro. The inhibition mechanism analysis results demonstrated that amlodipine and nifedipine might inhibit the metabolism of vonoprazan by a mixed type of competitive and non-competitive inhibition. However, the pharmacokinetic data of the vonoprazan prototype revealed that amlodipine affected vonoprazan in vivo while nifedipine did not. Thus, more attention should be paid when amlodipine is prescribed with vonoprazan. Furthermore, the changes in its carboxylic acid metabolites MI hinted at a complex situation. Molecular simulation suggested the CYP2B6 enzyme may contribute more to this than CYP3A4, and further inhibitory experiments preliminarily verified this speculation. In conclusion, the use of vonoprazan with cardiovascular drugs, especially amlodipine, should receive particular attention in clinical prescriptions.
The antitumor effect induced by an IL-2 ‘no-alpha’ mutein depends on changes in the CD8+ T lymphocyte/Treg cell balance

High doses of interleukin-2 (IL-2) have been used for the treatment of melanoma and renal cell carcinoma, but this therapy has limited efficacy, with a ~15% response rate. Remarkably, 7%–9% of patients achieve complete or long-lasting responses. Many patients treated with IL-2 experienced an expansion of regulatory T cells (Tregs), specifically the expansion of ICOS+ highly suppressive Tregs, which correlate with worse clinical outcomes. This partial efficacy together with the high toxicity associated with the therapy has limited the use of IL-2-based therapy. Taking into account the understanding of IL-2 structure, signaling, and in vivo functions, some efforts to improve the cytokine properties are currently under study. In previous work, we described an IL-2 mutein with higher antitumor activity and less toxicity than wtIL-2. Mutein was in silico designed for losing the binding capacity to CD25 and for preferential stimulation of effector cells CD8+ and NK cells but not Tregs. Mutein induces a higher anti-metastatic effect than wtIL-2, but the extent of the in vivo antitumor activity was still unexplored. In this work, it is shown that mutein induces a strong antitumor effect on four primary tumor models, being effective even in those models where wtIL-2 does not work. Furthermore, mutein can change the in vivo balance between Tregs and T CD8+ memory/activated cells toward immune activation, in both healthy and tumor-bearing mice. This change reaches the tumor microenvironment and seems to be the major explanation for mutein efficacy in vivo.
Monoamine oxidase inhibition in cigarette smokers: From preclinical studies to tobacco product regulation

Monoamine oxidase (MAO) activity is reduced in cigarette smokers and this may promote the reinforcing actions of nicotine, thereby enhancing the addictive properties of cigarettes. At present, it is unclear how cigarette smoking leads to MAO inhibition, but preclinical studies in rodents show that MAO inhibition increases nicotine self-administration, especially at low doses of nicotine. This effect of MAO inhibition develops slowly, likely due to plasticity of brain monoamine systems; studies relying on acute MAO inhibition are unlikely to replicate what happens with smoking. Given that MAO inhibition may reduce the threshold level at which nicotine becomes reinforcing, it is important to consider this in the context of very low nicotine content (VLNC) cigarettes and potential tobacco product regulation. It is also important to consider how this interaction between MAO inhibition and the reinforcing actions of nicotine may be modified in populations that are particularly vulnerable to nicotine dependence. In the context of these issues, we show that the MAO-inhibiting action of cigarette smoke extract (CSE) is similar in VLNC cigarettes and cigarettes with a standard nicotine content. In addition, we present evidence that in a rodent model of schizophrenia the effect of MAO inhibition to enhance nicotine self-administration is absent, and speculate how this may relate to brain serotonin systems. These issues are relevant to the MAO-inhibiting effect of cigarette smoking and its implications to tobacco product regulation.
Editorial: Training and testing in climbing

COPYRIGHT © 2022 Andersen, Baláš, Michailov and Saeterbakken. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Training and testing in climbing
Identifying the natural reserve area of Cistanche salsa under the effects of multiple host plants and climate change conditions using a maximum entropy model in Xinjiang, China

Cistanche salsa (C. A. Mey.) G. Beck, a holoparasitic desert medicine plant with multiple hosts, is regarded as a potential future desert economic plant. However, as a result of excessive exploitation and poaching, its wild resources have become scarce. Thus, before developing its desert economic value, this plant has to be protected, and the identification of its natural reserve is currently the top priority. However, in previous nature reserve prediction studies, the influence of host plants has been overlooked, particularly in holoparasitic plants with multiple hosts. In this study, we sought to identify the conservation areas of wild C. salsa by considering multiple host–plant interactions and climate change conditions using the MaxEnt model. Additionally, a Principal Component Analysis (PCA) was used to reduce the autocorrelation between environmental variables. The effects of the natural distribution of the host plants in terms of natural distribution from the perspective of niche similarities and extrapolation detection were considered by filtering the most influential hosts: Krascheninnikovia ceratoides (Linnaeus), Gueldenstaedt, and Nitraria sibirica Pall. Additionally, the change trends in these hosts based on climate change conditions combined with the change trends in C. salsa were used to identify a core protection area of 126483.5 km2. In this article, we corrected and tried to avoid some of the common mistakes found in species distribution models based on the findings of previous research and fully considered the effects of host plants for multiple-host holoparasitic plants to provide a new perspective on the prediction of holoparasitic plants and to provide scientific zoning for biodiversity conservation in desert ecosystems. This research will hopefully serve as a significant reference for decision-makers.
Inside the lungs of COVID-19 disease CURRENT STATUS: POSTED

In the setting of COVID-19 pandemic, only few data regarding lung pathology induced by SARS-CoV-2 is available, especially without medical intervention interacting with the natural evolution of the disease. We present here the first case of forensic autopsy of a COVID-19 fatality occurring in confinement and in a young female. Diagnosis was made at necropsy and lung histology revealed diffuse alveolar damage, edema and interstitial pneumonia with a geographically heterogeneous pattern, affecting mostly central part of the lungs. This death related to COVID-19 pathology highlights the heterogeneity and severity of central lung lesions when the disease naturally evolves.
An Experimental Study and a Numerical Simulation of the Turbulent Flow under the Vortex Finder of a Cyclone Separator

An experimental study and a numerical simulation are presented concerning the three dimensional turbulent flow of air in a cyclone separator in the region underneath the vortex finder. The computations are carried out using the Fluent CFD code. The turbulence effects on the mean flow are taken into account using the standard k- (cid:304) model and the standard Reynolds stress Model (RSM). The axial and tangential mean velocity components and the turbulence intensities are measured using Laser Doppler Anemometry. The LDA system is mounted in such a way that radial traverses at different angles of the cyclone cylindrical geometry and at different axial positions could be possible. The obtained results show interesting phenomena such as the three dimensional nature of the flow behaviour, the turbulence decay and its evolution towards an isotropic state in the quasi-free vortex region as the flow proceeds downstream in the cyclone. In the region underneath the vortex finder, the surface separating the descending and the ascending streams (set of points where the axial velocity component is nil) is located approximately in the fictitious prolongation of the vortex finder cylindrical wall. The existence of a quasi-forced vortex in the central region of the cyclone surrounded by a coaxial quasi-free vortex is confirmed. The radial distance separating the central vortex and the surrounding annular vortex, at a given angle and axial position, can be clearly defined as the distance from the axis to the point of intersection between two characteristic straight lines: the first line representing, ln Ut vs ln r, of slope +1, in the quasi-forced vortex and the second line, ln Ut vs ln r, of slope -1, in the quasi-free vortex, where Ut is the tangential component of the mean velocity. diffusion rate of j turbulent kinetic energy x i component of the unit vector normal to the wall production rate of j i u u x i component of the mean velocity tangential component of the mean velocity Reynolds stress component the distance normal to the wall dissipation rate of k dissipation rate of j i u u tangential coordinate laminar and turbulent kinematic viscosities laminar and turbulent Prandtl numbers associated with k laminar and turbulent Prandtl numbers associated with (cid:72) pressure-strain correlation terms
for Tackling Global Inequality in Labor Migration: Diaspora Mechanism and Migration Development

eScholarship provides open access, scholarly publishing services to the University of California and delivers a dynamic research platform to scholars worldwide. Abstract Globalization is a multifaceted phenomenon, of which temporary labor migration is the most socially profound and economically evident aspect. One of the immediate concerns related to increasing numbers of labor migrants is a correspondingly increasing inequality in their labor efforts vis-à-vis domestic workers; migrants’ social and legal status. Derived from such premise, this paper offers practical solutions tackling inequality, achieving social balance and migrants’ welfare. Our original propositions include Diaspora-led temporary labor migration mechanism and Migration Development Bank . Both policy instruments are prompted by analysis of modern labor markets and labor migration patterns. A state-managed temporary labor migration regime is recommended at the initial stages. Multilateral governmental agreements are prerequisite for legitimacy of the mechanism and formal protection of migrants’ and domestic workers’ rights. Fiscal policy is crucial in the final implementation of the proposed Diaspora mechanism. Collective welfare of the army of migrants is at stake with strong spillover effects in infrastructure, human capital and entrepreneurial projects in the home and host economies. Timely resolution of inequality issues shapes nation’s development path. This paper adds to the emerging research literature on the Diaspora studies. In the modern interlinked world Diasporas become real dominant actors in country development. Critical research within this theme must be encouraged and welcomed.
Automatic quality assessment and optimisation of quadratic time–frequency representations

A fully automatic method for optimising the smoothed-pseudo Wigner-Ville distribution is presented. An alternative view on time–frequency representations (TFRs) through correlation intensity landscapes is offered, and the notion of wanted and unwanted correlations and their balance is introduced which is introduced as the measure of quality. The problem of optimising TFRs is then formulated as the cost function based on this measure. With the differential evolution algorithm as the solver, the method's performance is tested on synthetic and real-life signals.
NORMOBARIC HYPEROXIA ON LOCAL MUSCLE FATIGUE

Yokoi, Y, Yanagihashi, R, Morishita, K, Goto, N, Fujiwara, T, and Abe, K. Recovery effects of repeated exposures to normobaric hyperoxia on local muscle fatigue. J Strength Cond Res 28(8): 2173–2179, 2014—Reported recovery effects of hyeroxia are conflicted. This study aimed to identify the effects and the mechanisms of normobaric hyperoxia on the recovery of local muscle fatigue, which is the most commonly encountered form of fatigue both daily and in training and competitions. Twelve male subjects performed 3 3 3 3 no less than 30 seconds of isometric quadriceps exercise at 70% of maximum voluntary isometric contraction (MVIC) separated by two 15-minute recovery sessions under 1 of 2 different atmospheric oxygen concentrations, one in normoxia (NOX; 20.9% O2) and another in hyperoxia (HOX; 30.0% O2). To assess the degree of fatigue and recovery, 4 parameters were used; MVIC, endurance time to exhaustion, blood lactate, and perceived exertion measured by a visual analog scale (VAS). Maximum voluntary isometric contraction improved an average by approximately 14% in HOX compared with NOX at the conclusion of the second recovery session. However, this was not associated with changes in other parameters because changes in endurance time, blood lactate, and VAS during the trials were similar. Based on our findings, we conclude that 2 sets of 15-minute recovery session in normobaric hyperoxia are effective for restoring MVIC from local muscle fatigue induced by intermittent intense exercises. For quicker recovery, athletes are recommended to repeat 15-minute recovery process under
REVIEW Fifteen Years after ‘‘Wingspread’’—Environmental Endocrine Disrupters and Human and Wildlife Health: Where We are Today and Where We Need to Go

systems. For example, scientists have expressed concern about the potential role of EDCs in increasing trends in early puberty in girls, obesity and type II diabetes in the United States and other populations. New concerns include complex endocrine alterations induced by mixtures of chemicals, an issue broadened due to the growing awareness that EDCs present in the environment include a variety of potent human and veterinary pharmaceutical products, personal care products, nutraceuticals and phytosterols. In this review we (1) address what have we learned about the effects of EDCs on ﬁsh, wildlife, and human health, (2) discuss representative animal studies on (anti)andro-gens, estrogens and 2,3,7,8-tetrachlorodibenzo- p -dioxin–like chemicals, and (3) evaluate regulatory proposals being considered for screening and testing these chemicals.