Miracle-dz/UniFAR-FTUs huggingface dataset:
Rv1717 Is a Cell Wall - Associated β-Galactosidase of Mycobacterium tuberculosis That Is Involved in Biofilm Dispersion

Understanding the function of conserved hypothetical protein (CHP)s expressed by a pathogen in the infected host can lead to better understanding of its pathogenesis. The present work describes the functional characterization of a CHP, Rv1717 of Mycobacterium tuberculosis (Mtb). Rv1717 has been previously reported to be upregulated in TB patient lungs. Rv1717 belongs to the cupin superfamily of functionally diverse proteins, several of them being carbohydrate handling proteins. Bioinformatic analysis of the amino acid sequence revealed similarity to glycosyl hydrolases. Enzymatic studies with recombinant Rv1717 purified from Escherichia coli showed that the protein is a β-D-galactosidase specific for pyranose form rather than the furanose form. We expressed the protein in Mycobacterium smegmatis (Msm), which lacks its ortholog. In MsmRv1717, the protein was found to localize to the cell wall (CW) with a preference to the poles. MsmRv1717 showed significant changes in colony morphology and cell surface properties. Most striking observation was its unusual Congo red colony morphotype, reduced ability to form biofilms, pellicles and autoagglutinate. Exogenous Rv1717 not only prevented biofilm formation in Msm, but also degraded preformed biofilms, suggesting that its substrate likely exists in the exopolysaccharides of the biofilm matrix. Presence of galactose in the extracellular polymeric substance (EPS) has not been reported before and hence we used the galactose-specific Wisteria floribunda lectin (WFL) to test the same. The lectin extensively bound to Msm and Mtb EPS, but not the bacterium per se. Purified Rv1717 also hydrolyzed exopolysaccharides extracted from Msm biofilm. Eventually, to decipher its role in Mtb, we downregulated its expression and demonstrate that the strain is unable to disperse from in vitro biofilms, unlike the wild type. Biofilms exposed to carbon starvation showed a sudden upregulation of Rv1717 transcripts supporting the potential role of Rv1717 in Mtb dispersing from a deteriorating biofilm.
Lessons From Deep Neural Networks for Studying the Coding Principles of Biological Neural Networks

One of the central goals in systems neuroscience is to understand how information is encoded in the brain, and the standard approach is to identify the relation between a stimulus and a neural response. However, the feature of a stimulus is typically defined by the researcher's hypothesis, which may cause biases in the research conclusion. To demonstrate potential biases, we simulate four likely scenarios using deep neural networks trained on the image classification dataset CIFAR-10 and demonstrate the possibility of selecting suboptimal/irrelevant features or overestimating the network feature representation/noise correlation. Additionally, we present studies investigating neural coding principles in biological neural networks to which our points can be applied. This study aims to not only highlight the importance of careful assumptions and interpretations regarding the neural response to stimulus features but also suggest that the comparative study between deep and biological neural networks from the perspective of machine learning can be an effective strategy for understanding the coding principles of the brain.
Asian Admixture in European Echinococcus multilocularis Populations: New Data From Poland Comparing EmsB Microsatellite Analyses and Mitochondrial Sequencing

The cestode Echinococcus multilocularis is the causative agent of a severe zoonotic disease: alveolar echinococcosis (AE). The parasite is distributed over a vast area in northern Eurasia and North America, but the impact of AE on human health is highly uneven between different regions. One hypothetical reason for this difference in virulence may be the genetic structure of E. multilocularis which—based on mitochondrial sequences and EmsB microsatellite profiles—forms four distinct clades. These clades correspond approximately to their continents of origin: Asia, Europe, and North America, with a fourth clade apparently restricted to Mongolia and neighboring regions, even though this clade has not yet been described by EmsB genotyping. However, there are various records of genetic variants from the “wrong” region, e.g., “European” haplotypes in Western Canada, which may be the result of introduction or natural migration of host animals. One such example, prompting this study, is the recent record of an “Asian” mitochondrial haplotype in worms from foxes in Poland. At the time, this could not be confirmed by EmsB microsatellite analysis, a method that has proven to possess greater discriminatory power with the E. multilocularis nuclear genome than sequencing of mitochondrial markers. Therefore, worms collected from foxes in Poland were examined both by EmsB analysis and sequencing of the full mitochondrial cox1 gene in order to allocate the samples to the European or Asian cluster. Based on EmsB analyses of 349 worms from 97 Polish red foxes, 92% of the worms clearly showed “European-type” EmsB profiles, but 27 worms (8%) from seven foxes showed profiles that clustered with samples of Asian origin. According to cox1 sequences, a total of 18 worms from 8 foxes belonged to the Asian cluster of haplotypes. The two methods did not fully agree: only 13 worms from three foxes belonged to Asian clusters by both EmsB and cox1, whereas 18 worms from nine foxes belonged to different clusters, according to each marker. Cross-fertilization between worms of Asian origin and those from the European Polish population may explain these conflicting results. The presence of clearly Asian elements in the Polish E. multilocularis population could be the result of introduction of E. multilocularis with host animals (e.g., domestic dogs), or the migration of foxes. In the absence of genetic data from eastern European countries, especially those bordering Poland, it cannot be concluded whether this Asian admixture is typical for a larger area toward central/eastern Europe, or the Polish parasite population is the western extreme of a gradient where both European and Asian elements mingle. Further studies are needed on this subject, preferably using both mitochondrial sequencing and EmsB microsatellite analysis.
Deletion of LRP1 From Astrocytes Modifies Neuronal Network Activity in an in vitro Model of the Tripartite Synapse

The low-density lipoprotein receptor-related protein 1 (LRP1) is a transmembrane receptor that binds over 40 potential ligands and is involved in processes such as cell differentiation, proliferation, and survival. LRP1 is ubiquitously expressed in the organism and enriched among others in blood vessels, liver, and the central nervous system (CNS). There, it is strongly expressed by neurons, microglia, immature oligodendrocytes, and astrocytes. The constitutive LRP1 knockout leads to embryonic lethality. Therefore, previous studies focused on conditional LRP1-knockout strategies and revealed that the deletion of LRP1 causes an increased differentiation of neural stem and precursor cells into astrocytes. Furthermore, astrocytic LRP1 is necessary for the degradation of Aβ and the reduced accumulation of amyloid plaques in Alzheimer’s disease. Although the role of LRP1 in neurons has intensely been investigated, the function of LRP1 with regard to the differentiation and maturation of astrocytes and their functionality is still unknown. To address this question, we generated an inducible conditional transgenic mouse model, where LRP1 is specifically deleted from GLAST-positive astrocyte precursor cells. The recombination with resulting knockout events was visualized by the simultaneous expression of the fluorescent reporter tdTomato. We observed a significantly increased number of GLT-1 expressing astrocytes in LRP1-depleted astrocytic cultures in comparison to control astrocytes. Furthermore, we investigated the influence of astrocytic LRP1 on neuronal activity and synaptogenesis using the co-culture of hippocampal neurons with control or LRP1-depleted astrocytes. These analyses revealed that the LRP1-deficient astrocytes caused a decreased number of single action potentials as well as a negatively influenced neuronal network activity. Moreover, the proportion of pre- and postsynaptic structures was significantly altered in neurons co-cultured with LPR1-depleted astrocytes. However, the number of structural synapses was not affected. Additionally, the supernatant of hippocampal neurons co-cultured with LRP1-deficient astrocytes showed an altered set of cytokines in comparison to the control condition, which potentially contributed to the altered neuronal transmission and synaptogenesis. Our results suggest astrocytic LRP1 as a modulator of synaptic transmission and synaptogenesis by altering the expression of the glutamate transporter on the cell surface on astrocytes and the release of cytokines in vitro.
Novel Diagnostic Tools for Identifying Cognitive Impairment in Dogs: Behavior, Biomarkers, and Pathology

Canine cognitive dysfunction syndrome (CCDS) is a progressive neurodegenerative disorder in senior dogs that is mainly associated with decreased ability to learn and respond to stimuli. It is commonly under-diagnosed because behavioral changes are often attributed to the natural process of aging. In the present study, we used for the first time a comprehensive approach enabling early diagnosis of canine patients with mild cognitive disorders (MiCI). We included CAnine DEmentia Scale (CADES) questionnaires, biochemical parameters, and biomarkers in blood serum, and correlated them with post-mortem histopathological changes. The CADES questionnaires enabled us to identify MiCI dogs developing changes mainly in domains corresponding to social interaction and spatial orientation, which seems to be crucial for delineating early cognitive disorders. Biochemical analyses in these dogs showed slightly elevated liver enzyme parameters (AST and ALT) and significantly decreased sodium and chloride levels in blood serum. Furthermore, we describe for the first time a significant increase of neurofilament light chain (NFL) in blood serum of MiCI dogs, compared to normal aging seniors and young controls, but no changes in TAU protein and amyloid-β (Aβ42) peptide levels. In canine brains with cognitive impairment, amyloid plaques of mainly diffuse and dense types were detected. Furthermore, activated microglia with amoeboid body and dystrophic processes occurred, in some cases with spheroidal and bulbous swellings. On the other hand, no TAU pathology or neurofibrillary tangles were detected. These results suggest that a combination of CADES questionnaire mainly with CNS injury biomarker (NFL) and with biochemical parameters (ALT, AST, Na, and Cl) in blood serum may predict CCDS in senior dogs.
How Stress Facilitates Phenotypic Innovation Through Epigenetic Diversity

Climate adaptation through phenotypic innovation will become the main challenge for plants during global warming. Plants exhibit a plethora of mechanisms to achieve environmental and developmental plasticity by inducing dynamic alterations of gene regulation and by maximizing natural variation through large population sizes. While successful over long evolutionary time scales, most of these mechanisms lack the short-term adaptive responsiveness that global warming will require. Here, we review our current understanding of the epigenetic regulation of plant genomes, with a focus on stress-response mechanisms and transgenerational inheritance. Field and laboratory-scale experiments on plants exposed to stress have revealed a multitude of temporally controlled, mechanistic strategies integrating both genetic and epigenetic changes on the genome level. We analyze inter- and intra-species population diversity to discuss how methylome differences and transposon activation can be harnessed for short-term adaptive efforts to shape co-evolving traits in response to qualitatively new climate conditions and environmental stress.
Exploring Brand Hate and the Association Between Similar Competitor Offer and Brand Equity: A Moderated-Mediation Model

Using the assumptions of Sternberg (2003) Duplex Theory of Hate, the present study reveals the combined effects of similar competitor offer and narcissistic personality on brand equity through the underlying mechanism of brand hate. Specifically, we hypothesize that brand hate mediates the relationship between similar competitor offer and brand equity. Moreover, we propose that similar competitor offer and brand hate relationship are stronger for narcissistic individuals. By employing a multi-wave time-lagged research design, we collected data from a sample of (N = 338) dairy product consumers in Pakistan. The findings of moderated-mediation regression analyses indicate that (a) Brand hate mediates the relationship between similar competitor offer and brand equity; and (b) Narcissistic personality moderates a similar competitor offer and brand hate relationship such that a high similar competitor offer led to greater brand hate when narcissism was high. Furthermore, conditional indirect effects reveal that brand hate mediates the relationship between similar competitor offer and brand equity only with individuals exhibiting narcissistic personality traits. The current study offers great insights to managers that by managing similar competitor offer, they can manage the development of brand hate, which can subsequently effect brand equity. Moreover, by profiling customers on the basis of their personalities, marketing managers can effectively invest only in customers with positive tendencies. The current study is unique in that it highlights new avenues in existing research by extending the nascent domain of brand hate in consumer–brand relationships.
Cell Type-Specific Predictive Models Perform Prioritization of Genes and Gene Sets Associated With Autism

Bulk transcriptomic analyses of autism spectrum disorder (ASD) have revealed dysregulated pathways, while the brain cell type-specific molecular pathology of ASD still needs to be studied. Machine learning-based studies can be conducted for ASD, prioritizing high-confidence gene candidates and promoting the design of effective interventions. Using human brain nucleus gene expression of ASD and controls, we construct cell type-specific predictive models for ASD based on individual genes and gene sets, respectively, to screen cell type-specific ASD-associated genes and gene sets. These two kinds of predictive models can predict the diagnosis of a nucleus with known cell type. Then, we construct a multi-label predictive model for predicting the cell type and diagnosis of a nucleus at the same time. Our findings suggest that layer 2/3 and layer 4 excitatory neurons, layer 5/6 cortico-cortical projection neurons, parvalbumin interneurons, and protoplasmic astrocytes are preferentially affected in ASD. The functions of genes with predictive power for ASD are different and the top important genes are distinct across different cells, highlighting the cell-type heterogeneity of ASD. The constructed predictive models can promote the diagnosis of ASD, and the prioritized cell type-specific ASD-associated genes and gene sets may be used as potential biomarkers of ASD.
Specular Highlight Detection Based on Color Distribution for Endoscopic Images

Endoscopic imaging systems have been widely used in disease diagnosis and minimally invasive surgery. Practically, specular reflection (a.k.a. highlight) always exists in endoscopic images and significantly affects surgeons’ observation and judgment. Motivated by the fact that the values of the red channel in nonhighlight area of endoscopic images are higher than those of the green and blue ones, this paper proposes an adaptive specular highlight detection method for endoscopic images. Specifically, for each pixel, we design a criterion for specular highlight detection based on the ratio of the red channel to both the green and blue channels. With the designed criteria, we take advantage of image segmentation and then develop an adaptive threshold with respect to the differences between the red channel and the other ones of neighboring pixels. To validate the proposed method, we conduct experiments on clinical data and CVC-ClinicSpec open database. The experimental results demonstrate that the proposed method yields an averaged Precision, Accuracy, and F1-score rate of 88.76%, 99.60% and 72.56%, respectively, and outperforms the state-of-the-art approaches based on color distribution reported for endoscopic highlight detection.
A Novel INCNS Score for Prediction of Mortality and Functional Outcome of Comatose Patients

Objectives: The purpose of this study was to verify the veracity and reliability of the INCNS score for prediction of neurological ICU (NICU) mortality and 3-month functional outcome and mortality in comatose patients. Methods: In this prospective study, data of the patients admitted to NICU from January 2013 to January 2019 were collected for validation. The 3-month functional outcomes were evaluated using modified Rankin Scale (mRS). By using the receiver operating characteristics curve (ROC) analysis, we compared the INCNS score with Glasgow Coma Scale (GCS), Full Outline of Un-Responsiveness Score (FOUR) and Acute Physiology and Chronic Health Evaluation II (APACHE II) for assessment of the predictive performance of these scales for 3-month functional outcome and mortality and NICU mortality performed at 24- and 72-h after admission to the NICU. Results: Totally 271 patients were used for evaluation; the INCNS score achieved an AUC (area under the receiver operating characteristic curve) of 0.766 (95% CI: 0.711–0.815) and 0.824 (95% CI: 0.774–0.868) for unfavorable functional outcomes, an AUC of 0.848 (95% CI: 0.800–0.889) and 0.892 (95% CI: 0.848–0.926) for NICU mortality, and an AUC of 0.811 (95% CI: 0.760–0.856) and 0.832 (95% CI: 0.782–0.874) for the 3-month mortality after discharge from the NICU at 24- and 72-h. The INCNS score exhibited a significantly better predictive performance of mortality and 3-month functional outcomes than FOUR and GCS. There was no significant difference in predicting NICU mortality and 3-month functional outcomes between INCNS and APACHE II, but INCNS had better predictive performance of 3-month mortality than APACHE II. Conclusions: The INCNS score could be used for predicting the functional outcomes and mortality rate of comatose patients.
Developing an Instrument for Assessing Self-Efficacy in Data Mining and Analysis

With the continuous progress and penetration of automated data collection technology, enterprises and organizations are facing the problem of information overload. The demand for expertise in data mining and analysis is increasing. Self-efficacy is a pivotal construct that is significantly related to willingness and ability to perform a particular task. Thus, the objective of this study is to develop an instrument for assessing self-efficacy in data mining and analysis. An initial measurement list was developed based on the skills and abilities about executing data mining and analysis, and expert recommendations. A useful sample of 103 university students completed the online survey questionnaire. A 19-item four-factor model was extracted by exploratory factor analysis. Using the partial least squares-structural equation modeling technique (PLS-SEM), the model was cross-examined. The instrument showed satisfactory reliability and validity. The proposed instrument will be of value to researchers and practitioners in evaluating an individual’s abilities and readiness in executing data mining and analysis.
Impulsivity and Response Inhibition Related Brain Networks in Adolescents With Internet Gaming Disorder: A Preliminary Study Utilizing Resting-State fMRI

Background and Aims: Internet gaming disorder (IGD), as a relapse disease, has become a common mental health problem among Asian teenagers. Functional connections in the prefrontal lobo-striatum affect changes in impulsivity and inhibition. Therefore, exploration of the directional connections of the relevant brain regions in the prefrontal-striatal circuit and the synchronization level of the two hemispheres will help us to further understand the neural mechanism of IGD, which can provide guidance for the development of prevention and intervention strategies. Methods: Twenty-two adolescents with IGD, recruited through various channels, composed the IGD group. Twenty-six subjects, matching age, gender, and education level, were included in a recreational internet game users (RGUs) control group. Impulsivity and response inhibition were tested via general questionnaire, the Internet Addiction Test (IAT), the Barratt impulsivity scale-11 (BIS-11), and a Stroop color-word task. A Granger causality analysis (GCA) was used to calculate the directional connection between the prefrontal and striatum with the dorsolateral prefrontal cortex (DLPFC) as a region of interest (ROI). We chose voxel-mirrored homotopic connectivity (VMHC) to determine brain hemisphere functional connectivity in the prefrontal-striatal circuits. Results: We found significant differences in impulsivity between the IGD group and RGU group, with members of the IGD group exhibiting higher impulsivity. Additionally, the response inhibition of adolescents with IGD in the Stroop color-word task was impaired. There was a significant difference in the directed connection of the left DLPFC and dorsal striatum between the IGD group and the RGU group. Conclusions: This study confirmed the role of prefrontal-striatal circuits in the neural mechanism of IGD in adolescents. In the IGD group, bilateral cerebral medial orbitofrontal cortex (mOFC) synchronization was significantly reduced, which indicated that mOFC signal transmission in both hemispheres of the brain might be affected by impulse behavior and impaired response inhibition.