Miracle-dz/UniFAR-FTUs huggingface dataset:
Visual modulation of spectrotemporal receptive fields in mouse auditory cortex

Recent studies have established significant anatomical and functional connections between visual areas and primary auditory cortex (A1), which may be important for perceptual processes such as communication and spatial perception. However, much remains unknown about the microcircuit structure of these interactions, including how visual context may affect different cell types across cortical layers, each with diverse responses to sound. The present study examined activity in putative excitatory and inhibitory neurons across cortical layers of A1 in awake male and female mice during auditory, visual, and audiovisual stimulation. We observed a subpopulation of A1 neurons responsive to visual stimuli alone, which were overwhelmingly found in the deep cortical layers and included both excitatory and inhibitory cells. Other neurons for which responses to sound were modulated by visual context were similarly excitatory or inhibitory but were less concentrated within the deepest cortical layers. Important distinctions in visual context sensitivity were observed among different spike rate and timing responses to sound. Spike rate responses were themselves heterogeneous, with stronger responses evoked by sound alone at stimulus onset, but greater sensitivity to visual context by sustained firing activity following transient onset responses. Minimal overlap was observed between units with visual-modulated firing rate responses and spectrotemporal receptive fields (STRFs) which are sensitive to both spike rate and timing changes. Together, our results suggest visual information in A1 is predominantly carried by deep layer inputs and influences sound encoding across cortical layers, and that these influences independently impact qualitatively distinct responses to sound. Significance statement Multisensory integration is ubiquitous throughout the brain, including primary sensory cortices. The present study examined visual responses in primary auditory cortex, which were found in both putative excitatory and inhibitory neurons and concentrated in the deep cortical layers. Visual-modulated responses to sound were similarly observed in excitatory and inhibitory neurons but were more evenly distributed throughout cortical layers. Visual modulation moreover differed substantially across distinct sound response types. Transient stimulus onset spike rate changes were far less sensitive to visual context than sustained spike rate changes during the remainder of the stimulus. Spike timing changes were often modulated independently of spike rate changes. Audiovisual integration in auditory cortex is thus diversely expressed among cell types, cortical layers, and response types.
Expression of soluble methane monooxygenase in Escherichia coli enables methane conversion

Natural gas and biogas provide an opportunity to harness methane as an industrial feedstock. Bioconversion is a promising alternative to chemical catalysis, which requires extreme operating conditions and exhibits poor specificities. Though methanotrophs natively utilize methane, efforts have been focused on engineering platform organisms like Escherichia coli for synthetic methanotrophy. Here, a synthetic E. coli methanotroph was developed by engineering functional expression of the Methylococcus capsulatus soluble methane monooxygenase in vivo via expression of its cognate GroESL chaperone. Additional overexpression of E. coli GroESL further improved activity. Incorporation of an acetone formation pathway then enabled the conversion of methane to acetone in vivo, as validated via 13C tracing. This work provides the first reported demonstration of methane bioconversion to liquid chemicals in a synthetic methanotroph.
iRhom2 regulates ERBB signalling to promote KRAS-driven oncogenesis

Dysregulation of the ERBB/EGFR signalling pathway causes multiple types of cancer (1, 2). Accordingly, ADAM17, the primary shedding enzyme that releases and activates ERBB ligands, is tightly regulated. It has recently become clear that iRhoms, inactive members of the rhomboid-like superfamily, are regulatory cofactors for ADAM17 (3, 4). Here we show that oncogenic KRAS mutants target the cytoplasmic domain of iRhom2 to induce ADAM17-dependent shedding and the release of ERBB ligands. Activation of ERK1/2 by oncogenic KRAS induces the phosphorylation of iRhom2, recruitment of the phospho-binding 14-3-3 proteins, and consequent ADAM17-dependent shedding of ERBB ligands. In addition, cancer-associated mutations in iRhom2 act as sensitisers in this pathway by further increasing KRAS-induced shedding of ERBB ligands. This mechanism is conserved in lung cancer cells, where iRhom activity is required for tumour xenograft growth. In this context, the activity of oncogenic KRAS is modulated by the iRhom2-dependent release of ERBB ligands, thus placing iRhom2 as a central component of a positive feedback loop in lung cancer cells. Overall, the cytoplasmic domain of iRhom2 is a critical component of KRAS-induced oncogenesis of lung cancer cells. Both ADAM17 and iRhom2 have also been implicated in a wide range of other cancers (5–10), so the mechanism we have revealed may also have wider oncogenic significance.
Establishment of Gut Microbiome During Early Life and Its Relationship With Growth in Endangered Crested Ibis (Nipponia nippon)

Gut microbiota during early life could influence host fitness in vertebrates. Studies on how gut microbiota colonize the gut in birds using frequent sampling during early developmental stages and how shifts in microbiota diversity influence host growth are lacking. Here, we examine the microbiome profiles of 151 fecal samples from 14 young crested ibis (Nipponia nippon), an endangered bird species, collected longitudinally across 13 time points during the early stages of development and investigated their correlation with host growth. Gut diversity showed a non-linear change during development, which involved multiple colonization and extinction events, mainly associated with Proteobacteria and Firmicutes. Gut microbiota in young crested ibis became more similar with increasing age. In addition, gut microbiota exhibited a strong temporal structure and two specific developmental stages; the beginning of the latter stage coincided with the introduction of fresh loach, with a considerable increase in the relative abundance of Fusobacteria and several Firmicutes, which may be involved in lipid metabolism. Crested ibis chick growth rate was negatively correlated with gut microbiota diversity and negatively associated with the abundance of Halomonadaceae, Streptococci, Corynebacteriaceae, and Dietziaceae. Our findings highlight the importance of frequent sampling when studying microbiome development during early stages of development of vertebrates. The role of microbial diversity in host growth during the early stages of development of birds warrants further investigations.
Measuring intrusion detection capability: an information-theoretic approach

A fundamental problem in intrusion detection is what metric(s) can be used to objectively evaluate an intrusion detection system (IDS) in terms of its ability to correctly classify events as normal or intrusive. Traditional metrics (e.g., true positive rate and false positive rate) measure different aspects, but no single metric seems sufficient to measure the capability of intrusion detection systems. The lack of a single unified metric makes it difficult to fine-tune and evaluate an IDS. In this paper, we provide an in-depth analysis of existing metrics. Specifically, we analyze a typical cost-based scheme [6], and demonstrate that this approach is very confusing and ineffective when the cost factor is not carefully selected. In addition, we provide a novel information-theoretic analysis of IDS and propose a new metric that highly complements cost-based analysis. When examining the intrusion detection process from an information-theoretic point of view, intuitively, we should have less uncertainty about the input (event data) given the IDS output (alarm data). Thus, our new metric, CI D (Intrusion Detection Capability), is defined as the ratio of the mutual information between the IDS input and output to the entropy of the input. CI D has the desired property that: (1) It takes into account all the important aspects of detection capability naturally, i.e., true positive rate, false positive rate, positive predictive value, negative predictive value, and base rate; (2) it objectively provides an intrinsic measure of intrusion detection capability; and (3) it is sensitive to IDS operation parameters such as true positive rate and false positive rate, which can demonstrate the effect of the subtle changes of intrusion detection systems. We propose CI D as an appropriate performance measure to maximize when fine-tuning an IDS. The obtained operation point is the best that can be achieved by the IDS in terms of its intrinsic ability to classify input data. We use numerical examples as well as experiments of actual IDSs on various data sets to show that by using CI D, we can choose the best (optimal) operating point for an IDS and objectively compare different IDSs.
Développement de méthodes numériques et étude des phénomènes couplés d’écoulement, de rayonnement, et d’ablation dans les problèmes d’entrée atmosphérique

Cette these est centree sur le couplage entre les phenomenes d’ecoulement, d’ablation et de rayonnement au voisinage du point d’arret de vehicules d’entree atmospherique pourvus d’un systeme de protection thermique de type carbonephenolique. La recherche est divisee en trois parties : 1) le developpement de methodes numeriques et d’outils pour la simulation d’ecoulements hypersoniques hors equilibre autour de corps emousses, 2) la mise en oeuvre d’un nouveau modele de transport du rayonnement hors equilibre dans ces ecoulements, y compris dans les couches limites contaminees par les produits d’ablation, et 3) l’application de ces outils a des conditions reelles de vol.Les effets du couplage entre l’ablation et le rayonnement sont etudies pour les rentrees terrestres. Il est demontre que les produits d’ablation dans la couche limite peuvent augmenter le blocage radiatif a la surface du vehicule. Pour les conditions de flux maximum d’Apollo 4, les effets de couplage entre le rayonnement et l’ablation reduisent le flux conductif de 35%. L’accord avec les donnees radiometriques est excellent, ce qui valide partiellement la methode de couplage et la base de donnees radiatives. L’importance d’une modelisation precise du soufflage du carbone dans la couche limite est egalement etablie.
Congenital Anomalies Programmed by Maternal Diabetes and Obesity on Offspring of Rats

Embryo-fetal exposure to maternal disorders during intrauterine life programs long-term consequences for the health and illness of offspring. In this study, we evaluated whether mild diabetic rats that were given high-fat/high-sugar (HF/HS) diet presented maternal and fetal changes at term pregnancy. Female rats received citrate buffer (non-diabetic-ND) or streptozotocin (diabetic-D) after birth. According to the oral glucose tolerance test (OGTT), the experimental groups (n = 11 animals/group) were composed of non-diabetic and diabetic receiving standard diet (S) or HF/HS diet. High-fat/high-sugar diet (30% kcal of lard) in chow and water containing 5% sucrose and given 1 month before mating and during pregnancy. During and at the end of pregnancy, obesity and diabetes features were determined. After laparotomy, blood samples, periovarian fat, and uterine content were collected. The diabetic rats presented a higher glycemia and percentage of embryonic losses when compared with the NDS group. Rats DHF/HS presented increased obesogenic index, caloric intake, and periovarian fat weight and reduced gravid uterus weight in relation to the other groups. Besides, this association might lead to the inflammatory process, confirmed by leukocytosis. Obese rats (NDHF/HS and DHF/HS) showed higher triglyceride levels and their offspring with lower fetal weight and ossification sites, indicating intrauterine growth restriction. This finding may contribute to vascular alterations related to long-term hypertensive disorders in adult offspring. The fetuses from diabetic dams showed higher percentages of skeletal abnormalities, and DHF/HS dams still had a higher rate of anomalous fetuses. Thus, maternal diabetes and/or obesity induces maternal metabolic disorders that contribute to affect fetal development and growth.
Urinary Proteomics Identifying Novel Biomarkers for the Diagnosis and Phenotyping of Carotid Artery Stenosis

Background: Carotid artery stenosis (CAS) is caused by the formation of atherosclerotic plaques inside the arterial wall and accounts for 20–30% of all strokes. The development of an early, noninvasive diagnostic method and the identification of high-risk patients for ischemic stroke is essential to the management of CAS in clinical practice. Methods: We used the data-independent acquisition (DIA) technique to conduct a urinary proteomic study in patients with CAS and healthy controls. We identified the potential diagnosis and risk stratification biomarkers of CAS. And Ingenuity pathway analysis was used for functional annotation of differentially expressed proteins (DEPs). Furthermore, receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic values of DEPs. Results: A total of 194 DEPs were identified between CAS patients and healthy controls by DIA quantification. The bioinformatics analysis showed that these DEPs were correlated with the pathogenesis of CAS. We further identified 32 DEPs in symptomatic CAS compared to asymptomatic CAS, and biological function analysis revealed that these proteins are mainly related to immune/inflammatory pathways. Finally, a biomarker panel of six proteins (ACP2, PLD3, HLA-C, GGH, CALML3, and IL2RB) exhibited potential diagnostic value in CAS and good discriminative power for differentiating symptomatic and asymptomatic CAS with high sensitivity and specificity. Conclusions: Our study identified novel potential urinary biomarkers for noninvasive early screening and risk stratification of CAS.
State of the California Current 2019–2020: Back to the Future With Marine Heatwaves?

The California Current System (CCS) has experienced large fluctuations in environmental conditions in recent years that have dramatically affected the biological community. Here we synthesize remotely sensed, hydrographic, and biological survey data from throughout the CCS in 2019–2020 to evaluate how recent changes in environmental conditions have affected community dynamics at multiple trophic levels. A marine heatwave formed in the north Pacific in 2019 and reached the second greatest area ever recorded by the end of summer 2020. However, high atmospheric pressure in early 2020 drove relatively strong Ekman-driven coastal upwelling in the northern portion of the CCS and warm temperature anomalies remained far offshore. Upwelling and cooler temperatures in the northern CCS created relatively productive conditions in which the biomass of lipid-rich copepod species increased, adult krill size increased, and several seabird species experienced positive reproductive success. Despite these conditions, the composition of the fish community in the northern CCS remained a mixture of both warm- and cool-water-associated species. In the southern CCS, ocean temperatures remained above average for the seventh consecutive year. Abundances of juvenile fish species associated with productive conditions were relatively low, and the ichthyoplankton community was dominated by a mixture of oceanic warm-water and cosmopolitan species. Seabird species associated with warm water also occurred at greater densities than cool-water species in the southern CCS. The population of northern anchovy, which has been resurgent since 2017, continued to provide an important forage base for piscivorous fishes, offshore colonies of seabirds, and marine mammals throughout the CCS. Coastal upwelling in the north, and a longer-term trend in warming in the south, appeared to be controlling the community to a much greater extent than the marine heatwave itself.
Hypoxia Inducible Factors as Central Players in the Pathogenesis and Pathophysiology of Cardiovascular Diseases

Cardiovascular (CV) diseases are the major cause of death in industrialized countries. The main function of the CV system is to deliver nutrients and oxygen to all tissues. During most CV pathologies, oxygen and nutrient delivery is decreased or completely halted. Several mechanisms, including increased oxygen transport and delivery, as well as increased blood flow are triggered to compensate for the hypoxic state. If the compensatory mechanisms fail to sufficiently correct the hypoxia, irreversible damage can occur. Thus, hypoxia plays a central role in the pathogenesis and pathophysiology of CV diseases. Hypoxia inducible factors (HIFs) orchestrate the gene transcription for hundreds of proteins involved in erythropoiesis, glucose transport, angiogenesis, glycolytic metabolism, reactive oxygen species (ROS) handling, cell proliferation and survival, among others. The overall regulation of the expression of HIF-dependent genes depends on the severity, duration, and location of hypoxia. In the present review, common CV diseases were selected to illustrate that HIFs, and proteins derived directly or indirectly from their stabilization and activation, are related to the development and perpetuation of hypoxia in these pathologies. We further classify CV diseases into acute and chronic hypoxic states to better understand the temporal relevance of HIFs in the pathogenesis, disease progression and clinical outcomes of these diseases. We conclude that HIFs and their derived factors are fundamental in the genesis and progression of CV diseases. Understanding these mechanisms will lead to more effective treatment strategies leading to reduced morbidity and mortality.
Does More Sedentary Time Associate With Higher Risks for Sleep Disorder Among Adolescents? A Pooled Analysis

Purpose: To investigate the association between sedentary behavior and anxiety-induced sleep disorder at a global perspective. Methods:A total of 254,924 adolescents (mean age: 14.45 ± 1.42 years; 52.8% girls) who participated in the Global School-Based Student Health Survey were included for analysis. Self-reported questionnaires assessed anxiety-induced sleep disorder and sedentary behavior. Multivariable logistic regression analysis and countrywide meta-analysis were used for investigating the association between sedentary behavior and anxiety-included sleep disorder. Results:The results showed that sedentary time was linearly associated with higher OR of anxiety-related sleep disorder in adolescents across the countries and that 8 h or more per day increased the OR by 2.17 times. Countrywide meta-analysis showed that 8 h or more per day of sedentary behavior yielded an OR = 1.40 (95% CI = 1.34–1.46) of anxiety-induced sleep disorder. Moreover, the association between sedentary behavior and sleep anxiety was significant in adolescents over the age of 11 years regardless of sex. Conclusions:The findings from this study suggest that as sedentary behavior increases, sleep disorders also increase, independently of sex among adolescents. Effective preventive strategies are needed to be taken to decrease sedentary behavior that could be used to improve mental health and sleep quality among adolescents.
An Overview of Cell-Based Assay Platforms for the Solute Carrier Family of Transporters

The solute carrier (SLC) superfamily represents the biggest family of transporters with important roles in health and disease. Despite being attractive and druggable targets, the majority of SLCs remains understudied. One major hurdle in research on SLCs is the lack of tools, such as cell-based assays to investigate their biological role and for drug discovery. Another challenge is the disperse and anecdotal information on assay strategies that are suitable for SLCs. This review provides a comprehensive overview of state-of-the-art cellular assay technologies for SLC research and discusses relevant SLC characteristics enabling the choice of an optimal assay technology. The Innovative Medicines Initiative consortium RESOLUTE intends to accelerate research on SLCs by providing the scientific community with high-quality reagents, assay technologies and data sets, and to ultimately unlock SLCs for drug discovery.
Social Isolation, Loneliness and Well-Being: The Impact of WeChat Use Intensity During the COVID-19 Pandemic in China

This study is aimed to examine the impact of WeChat use intensity on social isolation, loneliness, and well-being during the lockdown period of the COVID-19 pandemic. Drawing on the regulatory loop model of loneliness, the notions of Internet Paradox, the Time Displacement hypothesis and previous literature on WeChat use intensity, we propose that lockdown loneliness (partially) mediates the relationship between lockdown WeChat use intensity and well-being (i.e., lockdown stress and lockdown life satisfaction). Moreover, we assume that lockdown WeChat use intensity moderates the relationship between lockdown social isolation and well-being (i.e., lockdown stress and lockdown life satisfaction) in both a direct and in an indirect way, that is through lockdown loneliness. The results from our Structural Equation Modeling analyses, using a sample of 1,805 Chinese respondents, indicate that all of our research hypotheses are confirmed. From this empirical work, it becomes clear that online social interactions, which are believed by many people to be able to compensate for the lack of offline social interactions during the COVID-19 lockdown period, in fact are endangering their mental health and life satisfaction instead. This article concludes with theoretical and practical implications of our study, followed by its limitations and recommendations for future research.
Non-enzymatic Transformation of Aflatoxin B1 by Pseudomonas geniculata m29

Aflatoxin B1 (AFB1) is the most harmful mycotoxin produced by filamentous fungi and presents a serious threat to human and animal health. Therefore, it is essential to protect humans and animals from AFB1-induced acute and chronic toxicity. In this study, Pseudomonas strain m29 having a high efficiency of AFB1 transformation was isolated from soil. The transformation ratio by m29 was more than 97% within 24 h, and the optimum temperature for transformation was 37°C. Moreover, the AFB1 transforming activity was mainly attributed to the cell-free supernatant of strain m29. The metabolite that plays a crucial role in AFB1 transformation is likely 1,2-dimethylhydrazine or 1,1-dimethylhydrazine, as identified by GC-MS and LC-MS analysis. AFB1 was transformed into a product with molecular formula C17H14O7. To the best of our knowledge, this is the first study of non-enzymatic AFB1 transformation by bacteria. Importantly, this AFB1 transformation mechanism could be universal to various microorganisms.