Miracle-dz/UniFAR-FTUs huggingface dataset:
Isotope-Assisted Metabolite Analysis Sheds Light on Central Carbon Metabolism of a Model Cellulolytic Bacterium Clostridium thermocellum

Cellulolytic bacteria have the potential to perform lignocellulose hydrolysis and fermentation simultaneously. The metabolic pathways of these bacteria, therefore, require more comprehensive and quantitative understanding. Using isotope tracer, gas chromatography-mass spectrometry, and metabolic flux modeling, we decipher the metabolic network of Clostridium thermocellum, a model cellulolytic bacterium which represents as an attractive platform for conversion of lignocellulose to dedicated products. We uncover that the Embden–Meyerhof–Parnas (EMP) pathway is the predominant glycolytic route whereas the Entner–Doudoroff (ED) pathway and oxidative pentose phosphate pathway are inactive. We also observe that C. thermocellum's TCA cycle is initiated by both Si- and Re-citrate synthase, and it is disconnected between 2-oxoglutarate and oxaloacetate in the oxidative direction; C. thermocellum uses a citramalate shunt to synthesize isoleucine; and both the one-carbon pathway and the malate shunt are highly active in this bacterium. To gain a quantitative understanding, we further formulate a fluxome map to quantify the metabolic fluxes through central metabolic pathways. This work represents the first global in vivo investigation of the principal carbon metabolism of C. thermocellum. Our results elucidate the unique structure of metabolic network in this cellulolytic bacterium and demonstrate the capability of isotope-assisted metabolite studies in understanding microbial metabolism of industrial interests.
Deep Adaptive Temporal Pooling for Activity Recognition

Deep neural networks have recently achieved competitive accuracy for human activity recognition. However, there is room for improvement, especially in modeling of long-term temporal importance and determining the activity relevance of different temporal segments in a video. To address this problem, we propose a learnable and differentiable module: Deep Adaptive Temporal Pooling (DATP). DATP applies a self-attention mechanism to adaptively pool the classification scores of different video segments. Specifically, using frame-level features, DATP regresses importance of different temporal segments, and generates weights for them. Remarkably, DATP is trained using only the video-level label. There is no need of additional supervision except video-level activity class label. We conduct extensive experiments to investigate various input features and different weight models. Experimental results show that DATP can learn to assign large weights to key video segments. More importantly, DATP can improve training of frame-level feature extractor. This is because relevant temporal segments are assigned large weights during back-propagation. Overall, we achieve state-of-the-art performance on UCF101, HMDB51 and Kinetics datasets.
Developmental Constraints on Genome Evolution in Four Bilaterian Model Species

Developmental constraints on genome evolution have been suggested to follow either an early conservation model or an “hourglass” model. Both models agree that late development strongly diverges between species, but debate on which developmental period is the most conserved. Here, based on a modified “Transcriptome Age Index” approach, i.e. weighting parameters by expression level, we analyzed the constraints acting on three evolutionary traits of protein coding genes (strength of purifying selection on protein sequences, phyletic age, and duplicability) in four species: nematode worm C. elegans, fly D. melanogaster, zebrafish D. rerio and mouse M. musculus. In general, we found that both models can be supported by different genomic properties. The evolution of phyletic age and of duplicability follow an early conservation model in all species, but sequence evolution follows different models in different species: an early conservation model in fly, and an hourglass model in both zebrafish and mouse. Further analyses indicate that stronger purifying selection on sequences in early development of fly and during the morphological ‘phylotypic’ period of zebrafish and mouse are driven by temporal pleiotropy of these genes. In addition, we report evidence that expression in late development is enriched with retrogenes, which usually lack efficient regulatory elements. This implies that expression in late development could facilitate transcription of new genes, and provide opportunities for acquisition of function. Finally, in nematode, we suggest that dosage imbalance could be one of the main factors that cause depleted expression of high duplicability genes in early development.
How dependent is the alcohol industry on heavy drinking in England?

AIMS To understand the extent of the alcohol industry's financial dependence on drinking above government low-risk guidelines in England. DESIGN Scenario modelling using descriptive analyses of pooled data from the 2013 and 2014 waves of two nationally representative surveys: the Health Survey for England (HSE) and the Living Costs and Food Survey (LCF). We estimated the proportion of alcohol sales revenue accounted for by drinkers above guideline levels, and how this varies between different beverage and retailer types. We then estimated the impact on sales revenue if the entire population reduced their drinking to within guideline levels, as well as the average price increases necessary to compensate for such a loss of revenue. SETTING England. PARTICIPANTS A total of 16 872 individual (HSE) and 9975 household (LCF) survey respondents. MEASUREMENTS Transaction-level estimates of volume of alcohol purchased and price paid by beverage type and trade sector. FINDINGS Those drinking above guideline levels are estimated to account for 68% of total alcohol sales revenue in 2013/14: 81% of off-trade revenue and 60% of on-trade revenue. This represents 77% of beer, 70% of cider, 66% of wine and 50% of spirits sales value. The heaviest drinking 4% of the population account for 30% of all consumption and 23% of all industry revenue. If all consumers reduced their drinking to within guideline levels, alcohol sales revenue could decline by 38% (£13 billion). To mitigate this loss, average prices paid would have to rise substantially-for example, by £2.64 for a pint of on-trade beer or £12.25 for a 70 cl bottle of off-trade spirits. CONCLUSIONS In England, the alcohol industry appears to be highly financially dependent upon heavy drinking, and might face significant financial losses were consumers to drink within guideline levels.
Form Follows Function: An Investigation Into the Categorical Boundary of Surprise

The concept of basic emotions has been widely accepted in explaining human behavior. Yet, there is still no consensus on the distinctiveness of surprise. This study tried to compare the discreteness of surprise with that of other basic emotions in terms of their categorical distinctiveness. For this study, 27 undergraduates were recruited, and a new set of morphing sequences of different emotional expressions from two young Chinese posers was created. The results show that surprise is over-generalized to the perception of fear and that the categorical boundary is less discrete than for other emotional expression pairs. This blending is perhaps due to their confusion on both the perceptual and production levels. Additionally, a choice between external and internal validity when picking emotional expression stimuli is also discussed.
NF-κB-94ins/del ATTG Genotype Contributes to the Susceptibility and Imbalanced Th17 Cells in Patients with Immune Thrombocytopenia

Background The NLRP3 inflammasome plays important roles in the pathogenesis of autoimmune diseases. However, the role of the NLRP3 inflammasome in the pathophysiology of immune thrombocytopenia (ITP) remains unclear. Methods RT-PCR was used to examine the polymorphism and expression of genes involved in the NLRP3 inflammasome in ITP patients. T helper cells and apoptosis of PBMC from ITP patients were analyzed by flow cytometry. The antiplatelet autoantibodies in plasma were determined by modified monoclonal antibody-specific immobilization of platelet antigens (MAIPA). Results We found that the NF-κB-94ins/del ATTG genotype contributed to the susceptibility of ITP. Furthermore, the platelet counts of ITP patients with the WW genotype or WD genotype were lower than those with the DD genotype of NF-κB-94ins/del ATTG. Compared with controls, NF-κB gene expression was significantly decreased and WW or WD genotype ITP patients displayed higher mRNA expression than DD individuals. Similarly, the mRNA expression of NLRP3 was also increased in the WW genotype. There was a significant gene dose effect of the percentage of Th17 cells for the WW, WD, and DD genotypes (WW < WD < DD) in the unstimulated group and no significant difference was found after being stimulated. The activation of the NLRP3 inflammasome could upregulate Th17 in ITP patients. Conclusion The NF-κB-94ins/del ATTG genotype might serve as a novel biomarker and potential target for ITP.
CDKN2A Depletion Causes Aneuploidy and Enhances Cell Proliferation in Non-Immortalized Normal Human Cells

Abstract Aneuploidy is a common feature of cancer cells and may contribute to cellular transformation and cancer development. In this study, we found that significant down-regulation of CDKN2A, CHEK2, CDCA8, TP53BP1, and CCNDBP1 led to chromosome imbalances in two diploid non-immortalized human cell lines; however, only CDKN2A inhibition enhanced cell proliferation and additionally up-regulated three cell cycle control genes: CDCA8, AURKA, and CCND. These results confirm that CDKN2A is a tumor suppressor gene driving human cancer development by inducing cell aneuploidy and cell cycle up-regulation.
Comparative Secretome Analyses of Primary Murine White and Brown Adipocytes Reveal Novel Adipokines*

The secretome of white and brown primary murine adipocytes, with and without stimulation with norepinephrine (NE), has been determined by using mass spectrometry combined with AHA labeling and pulsed SILAC. The results reported reveal a comprehensive catalogue of novel adipokines secreted from white and brown adipocytes and responsive to NE. Given the beneficial effects of brown fat activation on systemic metabolism and its endocrine function, this study provides an archive of potential brown adipokines and biomarkers for activated brown fat. Graphical Abstract Highlights First comparative proteomic analysis of white and brown adipocyte secretomes. 100 novel adipokines differentially secreted from white versus brown adipocytes. Functionally enriched protein class changes in white and brown adipocytes. 200 novel, NE-responsive adipokines from brown adipocytes. The adipose organ, including white and brown adipose tissues, is an important player in systemic energy homeostasis, storing excess energy in form of lipids while releasing energy upon various energy demands. Recent studies have demonstrated that white and brown adipocytes also function as endocrine cells and regulate systemic metabolism by secreting factors that act locally and systemically. However, a comparative proteomic analysis of secreted factors from white and brown adipocytes and their responsiveness to adrenergic stimulation has not been reported yet. Therefore, we studied and compared the secretome of white and brown adipocytes, with and without norepinephrine (NE) stimulation. Our results reveal that carbohydrate-metabolism-regulating proteins are preferably secreted from white adipocytes, while brown adipocytes predominantly secrete a large variety of proteins. Upon NE stimulation, an increased secretion of known adipokines is favored by white adipocytes while brown adipocytes secreted higher amounts of novel adipokines. Furthermore, the secretory response between NE-stimulated and basal state was multifaceted addressing lipid and glucose metabolism, adipogenesis, and antioxidative reactions. Intriguingly, NE stimulation drastically changed the secretome in brown adipocytes. In conclusion, our study provides a comprehensive catalogue of novel adipokine candidates secreted from white and brown adipocytes with many of them responsive to NE. Given the beneficial effects of brown adipose tissue activation on its endocrine function and systemic metabolism, this study provides an archive of novel batokine candidates and biomarkers for activated brown adipose tissue.
Recent Trends in Wasp Nest Removal and Hymenoptera Stings in South Korea

Abstract To better understand the impact of social wasps on the health of people in South Korea, we analyzed requests to emergency services call centers for the removal of social wasp nests and the effect of Hymenoptera stings on human health between 2010 and 2014.There were 483,233 calls requesting removal of wasp nests and Hymenoptera stings caused 78,860 injuries and 49 deaths. The strong relationships between both the number of emergency calls and injuries, and urban density reflect the sensitivity of densely populated areas to potential threats from wasp and the increased awareness of the wasp nest removal service communicated by public education programs. We found that the removed nests belonged to 17 species of social wasp, with Polistes rothneyi koreanus Vecht and Vespa velutina nigrithorax du Buysson being the most prevalent. Problems associated with the invasive V. v. nigrithorax increased as the species became more widely distributed across the country and more abundant in urban areas. Increases in the incidence of sting injuries among males aged 40–69 between July and September were likely due to increased exposure during outdoor activities involving less-fit adults. In total, 1.5% of victims required hospitalization, of which 98.5% were treated as outpatients. Total medical costs associated with wasp stings over the 5-yr period were approximately 3.2 million USD. Although most wasp sting–related injuries were minor, some were serious, including fatalities, and were probably attributable to lack of education on wasp attack behavior.
A Comprehensive Review of Magnetoencephalography (MEG) Studies for Brain Functionality in Healthy Aging and Alzheimer's Disease (AD)

Neural oscillations were established with their association with neurophysiological activities and the altered rhythmic patterns are believed to be linked directly to the progression of cognitive decline. Magnetoencephalography (MEG) is a non-invasive technique to record such neuronal activity due to excellent temporal and fair amount of spatial resolution. Single channel, connectivity as well as brain network analysis using MEG data in resting state and task-based experiments were analyzed from existing literature. Single channel analysis studies reported a less complex, more regular and predictable oscillations in Alzheimer's disease (AD) primarily in the left parietal, temporal and occipital regions. Investigations on both functional connectivity (FC) and effective (EC) connectivity analysis demonstrated a loss of connectivity in AD compared to healthy control (HC) subjects found in higher frequency bands. It has been reported from multiplex network of MEG study in AD in the affected regions of hippocampus, posterior default mode network (DMN) and occipital areas, however, conclusions cannot be drawn due to limited availability of clinical literature. Potential utilization of high spatial resolution in MEG likely to provide information related to in-depth brain functioning and underlying factors responsible for changes in neuronal waves in AD. This review is a comprehensive report to investigate diagnostic biomarkers for AD may be identified by from MEG data. It is also important to note that MEG data can also be utilized for the same pursuit in combination with other imaging modalities.
Methylmercury Exposure and Developmental Outcomes in Tohoku Study of Child Development at 18 Months of Age

Seafood is an important component in a healthy diet and may contain methylmercury or other contaminants. It is important to recognize the risks and benefits of consuming seafood. A longitudinal prospective birth cohort study has been conducted to clarify the effects of neurotoxicants on child development—the Tohoku Study of Child Development (TSCD) in Japan. TSCD comprises two cohorts; a polychlorinated biphenyls (PCB) cohort (urban area) and a methylmercury cohort (coastal area). Our previous results from the coastal area showed prenatal methylmercury exposure affected psychomotor development in 18-month-olds, and boys appear to be more vulnerable to the exposure than girls. In this report, we have added the urban area cohort and we reanalyzed the impact of prenatal exposure to methylmercury, which gave the same results as before. These findings suggest prenatal exposure to low levels methylmercury may have adverse effects on child development, especially in boys.
Impact of similarity metrics on single-cell RNA-seq data clustering

Advances in high-throughput sequencing on single-cell gene expressions [single-cell RNA sequencing (scRNA-seq)] have enabled transcriptome profiling on individual cells from complex samples. A common goal in scRNA-seq data analysis is to discover and characterise cell types, typically through clustering methods. The quality of the clustering therefore plays a critical role in biological discovery. While numerous clustering algorithms have been proposed for scRNA-seq data, fundamentally they all rely on a similarity metric for categorising individual cells. Although several studies have compared the performance of various clustering algorithms for scRNA-seq data, currently there is no benchmark of different similarity metrics and their influence on scRNA-seq data clustering. Here, we compared a panel of similarity metrics on clustering a collection of annotated scRNA-seq datasets. Within each dataset, a stratified subsampling procedure was applied and an array of evaluation measures was employed to assess the similarity metrics. This produced a highly reliable and reproducible consensus on their performance assessment. Overall, we found that correlation-based metrics (e.g. Pearson's correlation) outperformed distance-based metrics (e.g. Euclidean distance). To test if the use of correlation-based metrics can benefit the recently published clustering techniques for scRNA-seq data, we modified a state-of-the-art kernel-based clustering algorithm (SIMLR) using Pearson's correlation as a similarity measure and found significant performance improvement over Euclidean distance on scRNA-seq data clustering. These findings demonstrate the importance of similarity metrics in clustering scRNA-seq data and highlight Pearson's correlation as a favourable choice. Further comparison on different scRNA-seq library preparation protocols suggests that they may also affect clustering performance. Finally, the benchmarking framework is available at http://www.maths. usyd.edu. au/u/SMS/bioinformatics/software.html.
Role of wnt5a in Metabolic Inflammation in Humans.

Context Common nutrition-associated diseases like obesity and type 2 diabetes are linked to chronic low-grade inflammation. The secreted glycopeptide wingless-type mouse mammary tumor virus integration site family member 5a (wnt5a) has been implicated in metabolic inflammation in rodent models, suggesting a potential treatment target. Data on the role of wnt5a in human physiology have yielded conflicting results. Objective Serum concentrations of wnt5a were measured in a cross-sectional cohort of 896 people to gain deeper insights into wnt5a physiology. Design Serum concentrations of wnt5a were measured by ELISA and related to several phenotyping and genotyping data. In vitro experiments were performed in THP-1 macrophages to examine potential molecular mechanisms. Results Wnt5a levels were significantly positively correlated to IL-6 and triglyceride levels. In subjects with diabetes, wnt5a levels were elevated and significantly correlated with fasting plasma glucose concentrations. Although wnt5a levels were not influenced by common single-nucleotide polymorphisms in the human wnt5a gene, environmental factors significantly altered wnt5a concentrations, as follows: (1) wnt5a levels were reduced in subjects with high nutritional load of the long-chain eicosatetraenoic acid independent of the total caloric intake and overall composition of the macronutrients, and (2) wnt5a levels were lower in humans with a high gut microbiome α diversity. In vitro experiments revealed that stimulation of the IL-6 receptor or the long-chain fatty acid receptor GPR40 directly affected wnt5a expression in human macrophages. Conclusion Our data suggest that wnt5a is important in linking inflammation to metabolism. The nutrition and the microbiome might be interesting targets to prevent and/or treat wnt5a-mediated metabolic inflammation.
Lexical learning in a new language leads to neural pattern similarity with word reading in native language

Previous neuroimaging studies have suggested similar neural activations for word reading in native and second languages. However, such similarities were qualitatively determined (i.e., overlapping activation based on traditional univariate activation analysis). In this study, using representational similarity analysis and an artificial language training paradigm, we quantitatively computed cross‐language neural pattern similarity to examine the modulatory effect of proficiency in the new language. Twenty‐four native Chinese speakers were trained to learn 30 words in a logographic artificial language for 12 days and scanned while performing a semantic decision task after 4‐day training and after 12‐day training. Results showed that higher proficiency in the new language was associated with higher cross‐language pattern similarity in select regions of the reading network.
Physician perceptions of recruitment and retention factors in an area with a regional medical campus

Background The factors that influence physicians to establish and maintain their practice in a region are variable. The presence of a regional medical campus (RMC) could influence physicians’ choice. The objective of this study was to explore the factors influencing physician recruitment and retention, and in particular the role of a RMC, in a region of Quebec. Methods A literature review of factors influencing physicians to stay in a rural area was conducted in order to create an interview guide. Questions were divided into sections: general information, family situation, medical training, career choice, current practice, intent to stay in the region, and impact of the RMC. Thirteen semi-structured individual interviews were conducted with practicing physicians. Data were analyzed using QDAMiner. Results Recruitment factors were divided into six major themes: type of practice, spousal interest, opportunity for teaching, training in a region, workforce planning, and quality of life. Participants identified positive and negative factors associated with retention. In both cases, family and quality of work environment were mentioned. The RMC was perceived as having important impacts on the quality of professional life, research, medical practice, and regional development. Conclusion This study highlights the role of RMCs in physician recruitment and retention via multiple impacts on the quality of practice of physicians working in the same area.