Miracle-dz/UniFAR-FTUs huggingface dataset:
Dysbiotic Lesional Microbiome With Filaggrin Missense Variants Associate With Atopic Dermatitis in India

Background: Atopic Dermatitis (AD) has been associated with the loss of function (LoF) mutations in Filaggrin (FLG) gene and increase in relative abundance of specific microbes in the lesional skin, predominantly in Caucasians. Our study aims to determine, in Indian AD patients, (a) the prevalence of FLG LoF and missense mutations, and (b) the nature and extent of dysbiosis and altered microbial pathways with and without mutations in FLG. AD patients (n = 34) and healthy controls (n = 54) were recruited from India in this study and shotgun sequencing was carried out in a subset of samples with adequate microbiome DNA concentration. Host DNA from the same subset of samples was subjected to FLG coding region sequencing and host-microbiome association was estimated. Results: The prevalence of FLG LoFs that are associated with AD globally were significantly lesser in our cases and controls (8.6%, 0%) than those reported in Europeans (27%, 2.6%). Staphylococcus aureus was present only on AD skin [abundance in Pediatric AD: 32.86%; Adult AD: 22.17%], but not on healthy skin on which Staphylococcus hominis (Adult controls: 16.43%, Adult AD: 0.20%; p = 0.002), Cutibacterium acnes (Adult controls:10.84%, Adult AD: 0.90%; p = 0.02), and Malassezia globosa (Adult controls: 8.89%, Adult AD: 0.005%; p = 0.001) were significantly more abundant. Microbial pathways mostly associated with skin barrier permeability, ammonia production and inflammation (Arginine and Proline metabolism, Histidine Metabolism and Staphylococcus aureus infection) were significantly enriched on AD skin metagenome. These pathways are also reported to impair antimicrobial peptide activity. Among AD patients with missense single nucleotide polymorphisms harboring “potentially damaging” alleles in FLG gene, damaging allele dosage was significantly (p < 0.02) positively correlated with relative abundance of phylum_Proteobacteria up to order_Pseudomonadales and negatively correlated with phylum_Firmicutes up to species_Staphylococcus aureus. Conclusion: Our study has provided evidence that host DNA profile is significantly associated with microbiome composition in the development of AD. Species and strain level analysis showed that the microbial pathways enriched in AD cases were mostly found in MRSA strains. These evidences can be harnessed to control AD by modulating the microbiome using a personalized strategy. Our findings on the association of FLG genotypes with the microbiome dysbiosis may pave the way for a personalized strategy to provide a more effective control of AD.
Regulation of the JAK2-STAT5 Pathway by Signaling Molecules in the Mammary Gland

Janus kinase 2 (JAK2) and signal transducers and activators of transcription 5 (STAT5) are involved in the proliferation, differentiation, and survival of mammary gland epithelial cells. Dysregulation of JAK2-STAT5 activity invariably leads to mammary gland developmental defects and/or diseases, including breast cancer. Proper functioning of the JAK2-STAT5 signaling pathway relies on crosstalk with other signaling pathways (synergistically or antagonistically), which leads to normal biological performance. This review highlights recent progress regarding the critical components of the JAK2-STAT5 pathway and its crosstalk with G-protein coupled receptor (GPCR) signaling, PI3K-Akt signaling, growth factors, inflammatory cytokines, hormone receptors, and cell adhesion.
Low Nitric Oxide Bioavailability Increases Renin Production in the Collecting Duct

In the kidney, the stimulation of renin production by the collecting duct (CD-renin) contributes to the development of hypertension. The CD is a major nephron segment for the synthesis of nitric oxide (NO), and low NO bioavailability in the renal medulla is associated with hypertension. However, it is unknown whether NO regulates renin production in the CD. To test the hypothesis that low intrarenal NO levels stimulate the production of CD-renin, we first examined renin expression in the distal nephron segments of CD-eNOS deficient mice. In these mice, specific CD-renin immunoreactivity was increased compared to wild-type littermates; however, juxtaglomerular (JG) renin was not altered. To further assess the intracellular mechanisms involved, we then treated M-1 cells with either 1 mM L-NAME (L-arginine analog), an inhibitor of NO synthase activity, or 1 mM NONOate, a NO donor. Both treatments increased intracellular renin protein levels in M-1 cells. However, only the inhibition of NOS with L-NAME stimulated renin synthesis and secretion as reflected by the increase in Ren1C transcript and renin protein levels in the extracellular media, respectively. In addition, NONOate induced a fast mobilization of cGMP and intracellular renin accumulation. These response was partially prevented by guanylyl cyclase inhibition with ODQ (1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1]. Accumulation of intracellular renin was blocked by protein kinase G (PKG) and protein kinase C (PKC) inhibitors. Our data indicate that low NO bioavailability increases CD-renin synthesis and secretion, which may contribute to the activation of intrarenal renin angiotensin system.
Brain–Behavior Associations for Risk Taking Depend on the Measures Used to Capture Individual Differences

Maladaptive risk taking can have severe individual and societal consequences; thus, individual differences are prominent targets for intervention and prevention. Although brain activation has been shown to be associated with individual differences in risk taking, the directionality of the reported brain–behavior associations is less clear. Here, we argue that one aspect contributing to the mixed results is the low convergence between risk-taking measures, especially between the behavioral tasks used to elicit neural functional markers. To address this question, we analyzed within-participant neuroimaging data for two widely used risk-taking tasks collected from the imaging subsample of the Basel–Berlin Risk Study (N = 116 young human adults). Focusing on core brain regions implicated in risk taking (nucleus accumbens, anterior insula, and anterior cingulate cortex), for the two tasks, we examined group-level activation for risky versus safe choices, as well as associations between local functional markers and various risk-related outcomes, including psychometrically derived risk preference factors. While we observed common group-level activation in the two tasks (notably increased nucleus accumbens activation), individual differences analyses support the idea that the presence and directionality of associations between brain activation and risk taking varies as a function of the risk-taking measures used to capture individual differences. Our results have methodological implications for the use of brain markers for intervention or prevention.
Computational Surveillance of Microbial Water Quality With Online Flow Cytometry

Automated flow cytometry (FCM) adapted to real-time quality surveillance provides high-temporal-resolution data about the microbial communities in a water system. The cell concentration calculated from FCM measurements indicates sudden increases in the number of bacteria, but can fluctuate significantly due to man-made and natural dynamics; it can thus obscure the presence of microbial anomalies. Cytometric fingerprinting tools enable a detailed analysis of the aquatic microbial communities, and could distinguish between normal and abnormal community changes. However, the vast majority of current cytometric fingerprinting tools use offline statistical computations which cannot detect anomalies immediately. Here, we present a computational model, entitled Microbial Community Change Detection (MCCD), which transforms microbial community characteristics into an online process control signal (herein called outlier score) that remains close to zero if the microbial community remains stable and increases with fluctuations in the community. The model is based on fingerprints and distance-based outlier calculations. We tested it in silico and in vitro by simulating acute contaminations to real-world water systems with large inherent microbial fluctuations. We showed that the outlier score was robust against these dynamic variations, while reliably detecting intentional contaminations. This model can be used with automated FCM to quickly detect potential microbiological contamination, and this especially when the time between treatment and distribution is very short.
Healthcare Transformation in Singapore With Artificial Intelligence

National University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, Singapore, 2 Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore, Division of Advanced Internal Medicine, National University Hospital, Singapore, Singapore, Group Chief Technology Office, National University Health System Singapore, Singapore, Singapore
An Empirical History of the US Postal Savings System

Abstract Seeking to reach the unbanked, the US Postal Savings System provided a federally insured savings alternative to traditional banks. Using novel data sets on postal deposits, demographic characteristics, and banks, we study how and by whom the system was used. We find the program was initially used by nonfarming immigrant populations for short-term saving, then as a safe haven during the Great Depression, and finally as long-term investments for the wealthy during the 1940s. Postal Savings was only a partial substitute for traditional banks, as locations with banks often still heavily used Postal Savings.
Regenerative Effect of a ROCK Inhibitor, Y-27632, on Excitotoxic Trauma in an Organotypic Culture of the Cochlea

In the past, most inner ear diseases were thought to start with the impairment of the sensory epithelium of the cochlea before subsequently progressing to secondary neural degeneration. However, recent studies show that loss of primary synapses accompanied by excitotoxic degeneration of peripheral axons is likely to be the underlying pathology in sensorineural hearing loss. Rho-associated coiled-coil containing protein kinase (ROCK) inhibition has been reported to have neuroprotective and regenerative effects on synaptic pathways. Therefore, we analyzed the effect of ROCK inhibition using Y-27632 in a model of peripheral axonal damage in the spiral ganglion neurons created using the glutamate agonists, N-methyl-D-aspartate (NMDA) and kainic acid, to induce excitotoxic trauma in the explanted cochlea. The number of axons projecting to hair cells in the cochlea treated with Y-27632 was significantly greater than those in the cochlea treated only with NMDA + kainic acid. Furthermore, there was a significant increase in synapses between the spiral ganglion and the inner hair cells in the cochlea treated with Y-27632. The findings of this study suggest that ROCK inhibition could be a potential strategy for the regeneration of peripheral axons in the spiral ganglion and synapse formation in the inner hair cells of a cochlea that has sustained excitotoxic injury, which is one of the primary etiologies of inner ear disease.
The Protective Role of the Carbohydrate Response Element Binding Protein in the Liver: The Metabolite Perspective

The Carbohydrate response element binding protein, ChREBP encoded by the MLXIPL gene, is a transcription factor that is expressed at high levels in the liver and has a prominent function during consumption of high-carbohydrate diets. ChREBP is activated by raised cellular levels of phosphate ester intermediates of glycolysis, gluconeogenesis and the pentose phosphate pathway. Its target genes include a wide range of enzymes and regulatory proteins, including G6pc, Gckr, Pklr, Prkaa1,2, and enzymes of lipogenesis. ChREBP activation cumulatively promotes increased disposal of phosphate ester intermediates to glucose, via glucose 6-phosphatase or to pyruvate via glycolysis with further metabolism by lipogenesis. Dietary fructose is metabolized in both the intestine and the liver and is more lipogenic than glucose. It also induces greater elevation in phosphate ester intermediates than glucose, and at high concentrations causes transient depletion of inorganic phosphate, compromised ATP homeostasis and degradation of adenine nucleotides to uric acid. ChREBP deficiency predisposes to fructose intolerance and compromised cellular phosphate ester and ATP homeostasis and thereby markedly aggravates the changes in metabolite levels caused by dietary fructose. The recent evidence that high fructose intake causes more severe hepatocyte damage in ChREBP-deficient models confirms the crucial protective role for ChREBP in maintaining intracellular phosphate homeostasis. The improved ATP homeostasis in hepatocytes isolated from mice after chronic activation of ChREBP with a glucokinase activator supports the role of ChREBP in the control of intracellular homeostasis. It is hypothesized that drugs that activate ChREBP confer a protective role in the liver particularly in compromised metabolic states.
Birds Perceive More Intraspecific Color Variation in Bird-Pollinated Than Bee-Pollinated Flowers

Pollinator-mediated selection is expected to constrain floral color variation within plant populations. Here, we test for patterns of constraint on floral color variation in 38 bee- and/or hummingbird-pollinated plant species from Colorado, United States. We collected reflectance spectra for at least 15 individuals in each of 1–3 populations of each species (total 78 populations) and modeled perceived color variation in both bee and bird visual spaces. We hypothesized that bees would perceive less intraspecific color variation in bee-pollinated species (vs. bird-pollinated species), and reciprocally, birds would perceive less color variation in bird-pollinated species (vs. bee-pollinated species). In keeping with the higher dimensionality of the bird visual system, birds typically perceived much more color variation than bees, regardless of plant pollination system. Contrary to our hypothesis, bees perceived equal color variation within plant species from the two pollination systems, and birds perceived more color variation in species that they pollinate than in bee-pollinated species. We propose hypotheses to account for the results, including reduced long-wavelength sensitivity in bees (vs. birds), and the ideas that potential categorical color vision in birds and larger cognitive capacities of birds (vs. bees) reduces their potential discrimination against floral color variants in species that they pollinate, resulting in less stabilizing selection on color within bird-pollinated vs. bee-pollinated species.
Calcium Oscillations in Pancreatic α-cells Rely on Noise and ATP-Driven Changes in Membrane Electrical Activity

In pancreatic α-cells, intracellular Ca2+ ([Ca2+]i) acts as a trigger for secretion of glucagon, a hormone that plays a key role in blood glucose homeostasis. Intracellular Ca2+ dynamics in these cells are governed by the electrical activity of voltage-gated ion channels, among which ATP-sensitive K+ (KATP) channels play a crucial role. In the majority of α-cells, the global Ca2+ response to lowering external glucose occurs in the form of oscillations that are much slower than electrical activity. These Ca2+ oscillations are highly variable as far as inter-spike intervals, shapes and amplitudes are concerned. Such observations suggest that Ca2+ dynamics in α-cells are much influenced by noise. Actually, each Ca2+ increase corresponds to multiple cycles of opening/closing of voltage gated Ca2+ channels that abruptly become silent, before the occurrence of another burst of activity a few tens of seconds later. The mechanism responsible for this intermittent activity is currently unknown. In this work, we used computational modeling to investigate the mechanism of cytosolic Ca2+ oscillations in α-cells. Given the limited population of KATP channels in this cell type, we hypothesized that the stochastic activity of these channels could play a key role in the sporadic character of the action potentials. To test this assumption, we extended a previously proposed model of the α-cells electrical activity (Diderichsen and Göpel, 2006) to take Ca2+ dynamics into account. Including molecular noise on the basis of a Langevin type description as well as realistic dynamics of opening and closing of KATP channels, we found that stochasticity at the level of the activity of this channel is on its own not able to produce Ca2+ oscillations with a time scale of a few tens of seconds. However, when taking into account the intimate relation between Ca2+ and ATP changes together with the intrinsic noise at the level of the KATP channels, simulations displayed Ca2+ oscillations that are compatible with experimental observations. We analyzed the detailed mechanism and used computational simulations to identify the factors that can affect Ca2+ oscillations in α-cells.
Review of ‘The variability spectrum of ecological communities: How common and rare species shape stability patterns’

One of the main findings is that the variability response to stochastic immigration perturbations is driven by rare species while the common species drive the response to environmental perturbations. While there have been previous suggestions of this differential responses of rare and common species to environmental fluctuations (e.g., using British birds, Saether et al. 2011, or within debates on forest tree communities dynamics, Chisholm et al. 2014), this is to my knowledge one of the first theoretical studies to investigate in great detail the role of species abundances, perturbation types and their interaction in shaping communitylevel variability. This work nicely builds on previous technical work by the authors, relating mathematically well-defined variability measures to more classic resilience measures, all of which are here described in a (relatively) accessible manner.
Local Similarity-Based Fuzzy Multiple Kernel One-Class Support Vector Machine

One-class support vector machine (OCSVM) is one of the most popular algorithms in the one-class classification problem, but it has one obvious disadvantage: it is sensitive to noise. In order to solve this problem, the fuzzy membership degree is introduced into OCSVM, which makes the samples with different importance have different influences on the determination of classification hyperplane and enhances the robustness. In this paper, a new calculation method of membership degree is proposed and introduced into the fuzzy multiple kernel OCSVM (FMKOCSVM). The combined kernel is used to measure the local similarity between samples, and then, the importance of samples is determined based on the local similarity between training samples, so as to determine the membership degree and reduce the impact of noise. The proposed membership requires only positive data in the calculation process, which is consistent with the training set of OCSVM. In this method, the noise has a smaller membership value, which can reduce the negative impact of noise on the classification boundary. Simultaneously, this method of calculating membership has a higher efficiency. The experimental results show that FMKOCSVM based on proposed local similarity membership is efficient and more robust to outliers than the ordinary multiple kernel OCSVMs.
Asynchronous Adaptive Fault-Tolerant Control for Networked Stochastic Unmanned Surface Vehicles with Multiple Types of Actuator Faults

This paper aims to design an asynchronous adaptive fault-tolerant controller for the networked stochastic unmanned surface vehicles (NSUSVs) subject to multiple types of actuator faults and external disturbance. The partial fault and bias fault of the actuator are taken into consideration simultaneously. By estimating online the unknown bias fault of the actuator and the external disturbances, the proposed adaptive fault-tolerant controller can automatically compensate for these impacts produced by actuator faults and external perturbation while preserving the uniformly ultimate boundedness of the solutions. Both the faulty actuator and the designed controller are asynchronous with the NSUSVs. Moreover, a mode-dependent adaptive event-triggered mechanism (AETM) is introduced in order to facilitate network resources utilization. Finally, the effectiveness and correctness of the proposed design scheme are verified by a numerical example.
Conformational behaviour of amphiphilic molecules in aqueous solution and at a water/air interface : computational studies at the molecular level

Previous experimental studies have indicated that the amphiphilic graft co-polymer polynorbornene-g-poly(ethylene oxide) (PNB-g-PEO) undergoes interesting conformational behaviour when placed at a water/air interface. This polymer adopts different conformations depending upon surface concentration, as elucidated through neutron reflectometry measurements. The work in this thesis details the preparation for, and execution of atomistic molecular dynamics simulations of this system at a range of surface concentrations. Three commonly used water models were assessed for computational expense and accuracy in the reproduction of key experimental properties, particularly density. It was found that the TIP4P water model was the most appropriate, and was therefore used to generate a water/vapour interface configuration. The OPLS-AA force field was then examined in detail on the basis of ab initio structural optimisation calculations on 1,2-dimethoxyethane (DME), a model molecule for poly (ethylene oxide) (PEO). Torsion parameters for the 0-C-C-O and C-O-C-C dihedral potentials were fitted to these ab initio data in an attempt to obtain a force field capable of reproducing the conformational behaviour of DME in the bulk liquid as measured previously by experiment. Using this fitted force field, fully atomistic simulations of PNB-g'-PEO at the water/vapour interface were performed at a range of surface concentrations coinciding with the experimental study. Excellent agreement was found between simulated and experimental neutron reflectivity profiles for low surface concentrations. Agreement at higher concentrations was slightly poorer, but still much better than that obtained in a previous simulation study without explicit water. Four force fields were then compared in "simulations of a PEO chain in aqueous solution. Dihedral angle analysis was performed on these PEO chains and compared to the behaviour of the PEO side chains in PNB-g-PEO. Agreement with conformational populations was confirmed between the two studies, however the frequency of conformational transitions was found to differ significantly between the two sets of simulation.