Miracle-dz/UniFAR-FTUs huggingface dataset:
The influence of aspect on the countability of Polish deverbal nominalizations: Evidence from an acceptability rating study

Abstract The paper presents the results of a study investigating a possible influence of the viewpoint (perfective vs. imperfective) and lexical (telic vs. atelic) aspect of Polish verbs on the countability of eventive nominalizations (substantiva verbalia) derived from these verbs. Polish substantiva verbalia preserve many properties of the base verbs, including the eventive meaning and aspectual morphology. Native speakers of Polish rated the acceptability of nominalizations in count and mass contexts. An effect of both viewpoint and lexical aspect was found in mass contexts, where aspectually delimited (perfective, accomplishment) nominalizations were less acceptable than non-delimited (imperfective, state) nominalizations. In count contexts, only an effect of the lexical aspect was clearly present, with accomplishment nominalizations being more acceptable than state nominalizations. The nominalizations were overall rated as more natural in mass than count constructions, regardless of the aspect. The results indicate that aspect plays a role in establishing the countability of a word, but it does not fully determine it.
Exploring zebrafish larvae as a COVID-19 model: probable SARS-COV-2 replication in the swim bladder

Animal models are essential to understand COVID-19 pathophysiology and for pre-clinical assessment of drugs and other therapeutic or prophylactic interventions. We explored the small, cheap and transparent zebrafish larva as a potential host for SARS-CoV-2. Bath exposure, as well as microinjection in the coelom, pericardium, brain ventricle, bloodstream, or yolk, did not result in detectable SARS-CoV-2 replication in wild-type larvae. However, when the virus was inoculated in the swim bladder, a modest increase in viral RNA was observed after 24 hours, suggesting a successful infection in some animals. This was confirmed by immunohistochemistry, with cells positive for SARS-CoV-2 nucleoprotein observed in the swim bladder. Several variants of concern were also tested with no evidence of increased infectivity in our model. Low infectivity of SARS-CoV-2 in zebrafish larvae was not due to the host type I interferon response, as comparable viral loads were detected in type I interferon-deficient animals. Mosaic overexpression of human ACE2 was not sufficient to increase SARS-CoV-2 infectivity in zebrafish embryos or in fish cells in vitro. In conclusion, wild-type zebrafish larvae appear mostly non-permissive to SARS-CoV-2, except in the swim bladder, an aerial organ sharing similarities with the mammalian lung.
Sensory readout accounts for adaptation

Sensory responses and behavior are strongly shaped by stimulus history. For instance, perceptual reports are sometimes biased towards previously viewed stimuli (serial dependence). While behavioral studies have pointed to both perceptual and post-perceptual origins of this phenomenon, neural data that could elucidate where these biases emerge is limited. We recorded fMRI responses while human participants (male and female) performed a delayed orientation discrimination task. While behavioral reports were attracted to the previous stimulus, response patterns in visual cortex were repelled. We reconciled these opposing neural and behavioral biases using a model where both sensory encoding and readout are shaped by stimulus history. First, neural adaptation reduces redundancy at encoding and leads to the repulsive biases that we observed in visual cortex. Second, our modeling work suggest that serial dependence is induced by readout mechanisms that account for adaptation in visual cortex. According to this account, the visual system can simultaneously improve efficiency via adaptation while still optimizing behavior based on the temporal structure of natural stimuli.
The influence of high salt intake on vascular responses of middle cerebral arteries to flow- induced dilation of Sprague-Dawley rats

Objective: Sprague-Dawley (SD) rats on high salt diet (HSD) remain normotensive and exhibit impaired relaxation responses to acetylcholine and hypoxia, as well as normotensive women on HSD, while there are no data of HSD effect on the flow- induced dilation (FID). The aim of the present study was to determine the effect of high salt intake on microvascular responses to flow-induced dilation in SD rats. Design and method: 19 male SD rats were divided in two groups: a) control group (N=10) and b) group of rats on HSD for 7 days (4% NaCl ; N=9). Prior to decapitation, rats were anesthetized with 75 mg/kg ketamine+2.5 mg/kg midazolam. Middle cerebral arteries were isolated and cannulated (DMT pressure myograph) for vascular reactivity measurements in response to stepwise increase in pressure (Δ10-Δ100), in the absence/presence of the NOS inhibitor L-NAME, COX- 1, 2 inhibitor indomethacin (INDO), selective inhibitor of microsomal CYP450 epoxidase activity MS-PPOH, and superoxide dismutase mimetic TEMPOL. To test differences among groups Two-way ANOVA was used, p<0.05 considered significant. Results: FID was reduced in HSD group at each pressure gradient, but significantly at Δ40, Δ60 (P<0.001) and Δ100 (P<0.05). The presence of L- NAME, INDO and MS-PPOH (independantly) significantly reduced FID in the control group at each pressure gradient (P<0.05) except Δ10. L- NAME and INDO reduced FID in HSD group, but L-NAME significantly reduces FID at Δ20 and Δ40 (P<0.05). The presence of TEMPOL restores FID in HSD group to control levels at pressure gradients Δ20-Δ100 (P<0.05), while in control group TEMPOL had no effect. Conclusions: These results demonstrate that: 1) High salt intake impaires vascular responses to FID ; 2) Reactive oxygen species - superoxide anion radical (O2-) may contribute to impaired FID in rats on high salt diet ; 3) Mechanisms of FID are different in control and HSD groups – while NO mediates FID in both groups of rats, metabolites of COX-1, 2, and EETs could also contribute to FID in control group of rats.
Human endogenous oxytocin and its neural correlates show adaptive responses to social touch based on recent social context

Both oxytocin (OT) and touch are key mediators of social attachment. In rodents, tactile stimulation elicits endogenous release of OT, potentially facilitating attachment and other forms of prosocial behavior, yet the relationship between endogenous OT and neural modulation remains unexplored in humans. Using serial sampling of plasma hormone levels during functional neuroimaging across two successive social interactions, we show that contextual circumstances of social touch facilitate or inhibit not only current hormonal and brain responses, but also calibrate later responses. Namely, touch from a male to his female romantic partner enhanced subsequent OT release for touch from an unfamiliar stranger, yet OT responses to partner touch were dampened following stranger touch. Hypothalamus and dorsal raphe activation reflected plasma OT changes during the initial interaction. In the subsequent social interaction, time- and context-dependent OT changes modulated precuneus and parietal-temporal cortex pathways, including a region of medial prefrontal cortex that also covaried with plasma cortisol. These findings demonstrate that hormonal neuromodulation during successive human social interactions is adaptive to social context, and point to mechanisms that flexibly calibrate receptivity in social encounters.
Tracing patterns of evolution and acquisition of drug resistant Aspergillus fumigatus infection from the environment using population genomics

Infections caused by opportunistic fungal pathogens are increasingly resistant to first-line azole antifungal drugs. However, despite its clinical importance, little is known about the extent to which susceptible patients acquire infection from drug resistant genotypes in the environment. Here, we present a population genomic analysis of the mould Aspergillus fumigatus from across the United Kingdom and Republic of Ireland. First, we show occurrences where azole resistant isolates of near identical genotypes were obtained from both environmental and clinical sources, indicating with high confidence the infection of patients with resistant isolates transmitted from the environment. Second, we find that the fungus is structured into two clades (‘A’ and ‘B’) with little interclade recombination and the majority of environmental azole resistance genetically clustered inside Clade A. Genome-scans show the impact of selective sweeps across multiple regions of the genome. These signatures of positive selection are seen in regions containing canonical genes encoding fungicide resistance in the ergosterol biosynthetic pathway, whilst other regions under selection have no defined function. Phenotyping identified genes in these regions that could act as modifiers of resistance showing the utility of reverse genetic approaches to dissect the complex genomic architecture of fungal drug resistance. Understanding the environmental drivers and genetic basis of evolving fungal drug resistance needs urgent attention, especially in light of increasing numbers of patients with severe viral respiratory tract infections who are susceptible to opportunistic fungal superinfections.
Latent functional connectivity underlying multiple brain states

Functional connectivity (FC) studies have predominantly focused on resting state, where ongoing dynamics are thought to reflect the brain’s intrinsic network architecture, which is thought to be broadly relevant because it persists across brain states (i.e., is state-general). However, it is unknown whether resting state is the optimal state for measuring intrinsic FC. We propose that latent FC, reflecting shared connectivity patterns across many brain states, better captures state-general intrinsic FC relative to measures derived from resting state alone. We estimated latent FC independently for each connection using leave-one-task-out factor analysis in 7 highly distinct task states (24 conditions) and resting state using fMRI data from the Human Connectome Project. Compared to resting-state connectivity, latent FC improves generalization to held-out brain states, better explaining patterns of connectivity and task-evoked activation. We also found that latent connectivity improved prediction of behavior outside the scanner, indexed by the general intelligence factor (g). Our results suggest that FC patterns shared across many brain states, rather than just resting state, better reflects state-general connectivity. This affirms the notion of “intrinsic” brain network architecture as a set of connectivity properties persistent across brain states, providing an updated conceptual and mathematical framework of intrinsic connectivity as a latent factor.
Ligand Strain Energy in Large Library Docking

While small molecule internal strain is crucial to molecular docking, using it in evaluating ligand scores has remained elusive. Here, we investigate a technique that calculates strain using relative torsional populations in the Cambridge Structural Database, enabling fast pre-calculation of these energies. In retrospective studies of large docking screens of the dopamine D4 receptor and of AmpC β-lactamase, where close to 600 docking hits were tested experimentally, including such strain energies improved hit rates by preferentially reducing high-scoring decoy molecules that were strained. In a 40 target subset of the DUD-E benchmark, we found two thresholds that usefully distinguished between ligands and decoys: one based on the total strain energy of the small molecules, and one based on the maximum strain allowed for any given torsion within them. Using these criteria, about 75% of the benchmark targets had improved enrichment after strain filtering. Relying on pre-calculated population distributions, this approach is rapid, taking less than 0.04 second to evaluate a conformation on a standard core, making it pragmatic for pre-calculating strain in even ultra-large libraries. Since it is scoring function agnostic, it may be useful to multiple docking approaches; it is openly available at http://tldr.docking. org
Rapid adaptation of a complex trait during experimental evolution of Mycobacterium tuberculosis

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), is a leading cause of death due to infectious disease. TB is not traditionally associated with biofilms, but M. tb biofilms are linked with drug and immune tolerance and there is increasing recognition of their contribution to the recalcitrance of TB infections. Here we used M. tb experimental evolution to investigate this complex phenotype and identify candidate loci controlling biofilm formation. We identified novel candidate loci, adding to our understanding of the genetic architecture underlying M. tb biofilm development. Under selective pressure to grow as a biofilm, regulatory mutations rapidly swept to fixation and were associated with changes in multiple traits including extracellular matrix production, cell size, and growth rate. Genetic and phenotypic paths to enhanced biofilm growth varied according to the genetic background of the parent strain, suggesting that epistatic interactions are important in M. tb adaptation to changing environments.
PKR-mediated stress response enhances dengue and Zika virus replication

ABSTRACT The mechanisms by which flaviviruses use non-canonical translation to support their replication in host cells are largely unknown. Here, we investigated how the integrated stress response (ISR), which promotes translational arrest by eIF2ɑ phosphorylation (p-eIF2ɑ), regulates flavivirus replication. During dengue virus (DENV) and Zika virus (ZIKV) infection, eIF2ɑ phosphorylation peaked at 24 hours post-infection and was dependent on protein kinase RNA-activated (PKR) but not type I interferon. The ISR is activated downstream of p-eIF2α during infection with either virus, but translation arrest only occurred following DENV4 infection. Despite this difference, both DENV4 and ZIKV replications were impaired in cells lacking PKR, independent of type I interferon/NF-kB signaling or cell viability. By using a ZIKV 5′-untranslated region (UTR) reporter system as a model, we found that this region of the genome is sufficient to promote an enhancement of viral mRNA translation in the presence of an active ISR. Together, we provide evidence that flaviviruses escape ISR translational arrest and co-opt this response to increase viral replication. IMPORTANCE One of the fundamental features that make viruses intracellular parasites is the necessity to use cellular translational machinery. Hence, this is a crucial checkpoint for controlling infections. Here, we show that dengue and Zika viruses, responsible for nearly 400 million infections every year worldwide, explore such control for optimal replication. Using immunocompetent cells, we demonstrate that arrest of protein translations happens after sensing of dsRNA and that the information required to avoid this blocking is contained in viral 5′-UTR. Our work, therefore, suggests that the non-canonical translation described for these viruses is engaged when the intracellular stress response is activated. One of the fundamental features that make viruses intracellular parasites is the necessity to use cellular translational machinery. Hence, this is a crucial checkpoint for controlling infections. Here, we show that dengue and Zika viruses, responsible for nearly 400 million infections every year worldwide, explore such control for optimal replication. Using immunocompetent cells, we demonstrate that arrest of protein translations happens after sensing of dsRNA and that the information required to avoid this blocking is contained in viral 5′-UTR. Our work, therefore, suggests that the non-canonical translation described for these viruses is engaged when the intracellular stress response is activated.
Selective remembering: Cue overlap enables pre-retrieval control of recollection

People often want to recall only currently relevant events, but this selective remembering is not always possible. We contrasted two candidate mechanisms: the overlap between retrieval cues and stored memory traces, and the ease of recollection. In two preregistered experiments (Ns = 28) we quantified recollection of targeted over non-targeted information using eventrelated potentials (ERPs). Participants viewed objects or heard object names, and one of these sources was designated as targets in each memory test. We manipulated cue overlap by probing memory with visual names (Experiment 1) or line drawings (Experiment 2). Results revealed that regardless of which source was targeted, the left parietal ERP effect was selective when test cues overlapped more with targeted than non-targeted information, despite consistently better memory for pictures. The data support the view that selection can act prior to recollection if there is sufficient overlap between retrieval cues and targeted versus competing memory traces.
Heritable variation in locomotion, reward sensitivity and impulsive behaviors in a genetically diverse inbred mouse panel

Drugs of abuse, including alcohol and stimulants like cocaine, produce effects that are subject to individual variability, and genetic variation accounts for at least a portion of those differences. Notably, research in both animal models and human subjects point towards reward sensitivity and impulsivity as being trait characteristics that predict relatively greater positive subjective responses to stimulant drugs. Here we describe use of the eight Collaborative Cross (CC) founder strains and multiple CC strains to examine the heritability of reward sensitivity and impulsivity traits, as well as genetic correlations between these measures and existing addiction-related phenotypes. Methods. Strains were all tested for activity in an open field and reward sensitivity (intake of chocolate BOOST®). Mice were then divided into two counterbalanced groups and underwent reversal learning (impulsive action and waiting impulsivity) or delay discounting (impulsive choice). Results. CC and founder mice demonstrate significant heritability for impulsive action, impulsive choice, waiting impulsivity, locomotor activity, and reward sensitivity, with each impulsive phenotype determined to be non-correlating, independent traits. This research was conducted within the broader, inter-laboratory effort of the Center for Systems Neurogenetics of Addiction (CSNA) to characterize CC and DO mice for multiple, cocaine abuse related traits. These data will facilitate the discovery of genetic correlations between predictive traits, which will then guide discovery of genes and genetic variants that contribute to addictive behaviors.
Discovery of target genes and pathways of blood trait loci using pooled CRISPR screens and single cell RNA sequencing

The majority of variants associated with complex traits and common diseases identified by genome-wide association studies (GWAS) map to noncoding regions of the genome with unknown regulatory effects in cis and trans. By leveraging biobank-scale GWAS data, massively parallel CRISPR screens and single cell transcriptome sequencing, we discovered target genes of noncoding variants for blood trait loci. The closest gene was often the target gene, but this was not always the case. We also identified trans-effects networks of noncoding variants when cis target genes encoded transcription factors, such as GFI1B and NFE2. We observed that GFI1B trans-target genes were enriched for GFI1B binding sites and fine-mapped GWAS variants, and expressed in human bone marrow progenitor cells, suggesting that GFI1B acts as a master regulator of blood traits. This platform will enable massively parallel assays to catalog the target genes of human noncoding variants in both cis and trans.
Mining Subsidence-Induced Microtopographic Effects Alter the Interaction of Soil Bacteria in the Sandy Pasture, China

The microtopographic changes induced by coal mining subsidence caused a series of environmental problems such as soil erosion, and vegetation degradation in the mining area. However, the corresponding influence on surface vegetation and soil characteristic in different parts of the slope was completely different. To understand soil and vegetation degradation in coal mines and their future ecological restoration, it was crucial to investigate the origin. The relationship between soil microbial community diversity, structure, and taxa in the slope of subsidence area of different topographic locations in Daliuta coal mine, Shannxi, China, was determined by high throughput sequencing and molecular ecological network analysis. The relationship between the bacterial communities, environmental factors, and soil physicochemical properties was also investigated. We found a new topographic trait formed by surface subsidence to deteriorate the living environment of vegetation and the bacterial community. The vegetation coverage, soil water content, organic matter, and urease and dehydrogenase activities decreased significantly (p < 0.05). Although soil bacterial community diversity in the subsidence area did not differ significantly, the dominant taxa in different topographic locations varied. The molecular ecological networks representing bacterial community structure and function were also totally different. The networks in the middle and the top of the slope tend to be more complicated, and the interaction between species is obviously stronger than that of the bottom. However, the network in the bottom slope approached simplicity, and weak interaction, predominantly cooperative, was observed within and between modules. Meanwhile, the double stress of aridity and the lack of carbon source induced by subsidence also enhanced the capacity of the soil bacterial community to metabolize complex carbon sources at the bottom of the slope.
Pharmacological Activities and Mechanisms of Hirudin and Its Derivatives - A Review

Hirudin, an acidic polypeptide secreted by the salivary glands of Hirudo medicinalis (also known as “Shuizhi” in traditional Chinese medicine), is the strongest natural specific inhibitor of thrombin found so far. Hirudin has been demonstrated to possess potent anti-thrombotic effect in previous studies. Recently, increasing researches have focused on the anti-thrombotic activity of the derivatives of hirudin, mainly because these derivatives have stronger antithrombotic activity and lower bleeding risk. Additionally, various bioactivities of hirudin have been reported as well, including wound repair effect, anti-fibrosis effect, effect on diabetic complications, anti-tumor effect, anti-hyperuricemia effect, effect on cerebral hemorrhage, and others. Therefore, by collecting and summarizing publications from the recent two decades, the pharmacological activities, pharmacokinetics, novel preparations and derivatives, as well as toxicity of hirudin were systematically reviewed in this paper. In addition, the clinical application, the underlying mechanisms of pharmacological effects, the dose-effect relationship, and the development potential in new drug research of hirudin were discussed on the purpose of providing new ideas for application of hirudin in treating related diseases.