Miracle-dz/UniFAR-FTUs huggingface dataset:
Aβ initiates brain hypometabolism and network dysfunction via NOX2 activation: a potential onset mechanism of Alzheimer’s disease

A predominant trigger and driver of sporadic Alzheimer’s disease (AD) is the synergy of brain oxidative stress and glucose hypometabolism starting at early preclinical stages. Oxidative stress damages macromolecules, while glucose hypometabolism impairs cellular energy supply and antioxidant defense. However, the exact cause of AD-associated glucose hypometabolism and its network consequences has remained unknown. Here we report NADPH oxidase 2 (NOX2) activation as the main initiating mechanism behind Aβ1-42-related glucose hypometabolism and network dysfunction. We utilize a combination of electrophysiology with real-time recordings of metabolic transients both ex- and in-vivo to show that Aβ1-42 induces oxidative stress and acutely reduces cellular glucose consumption followed by long-lasting network hyperactivity and abnormalities in the animal behavioral profile. Critically, all of these pathological changes were prevented by the novel bioavailable NOX2 antagonist GSK2795039. Our data provide the first direct experimental evidence for causes and consequences of AD-related brain glucose hypometabolism, and suggest that targeting NOX2-mediated oxidative stress is a promising approach to both the prevention and treatment of AD.Beta-amyloid induces brain hypometabolism, network hyperactivity, and behavioral changes via NADPH oxidase-mediated oxidative stress, suggesting a novel therapeutic target for Alzheimer’s disease treatment.
Ligilactobacillus salivarius Strains Isolated From the Porcine Gut Modulate Innate Immune Responses in Epithelial Cells and Improve Protection Against Intestinal Viral-Bacterial Superinfection

Previously, we constructed a library of Ligilactobacillus salivarius strains from the intestine of wakame-fed pigs and reported a strain-dependent capacity to modulate IFN-β expression in porcine intestinal epithelial (PIE) cells. In this work, we further characterized the immunomodulatory activities of L. salivarius strains from wakame-fed pigs by evaluating their ability to modulate TLR3- and TLR4-mediated innate immune responses in PIE cells. Two strains with a remarkable immunomodulatory potential were selected: L. salivarius FFIG35 and FFIG58. Both strains improved IFN-β, IFN-λ and antiviral factors expression in PIE cells after TLR3 activation, which correlated with an enhanced resistance to rotavirus infection. Moreover, a model of enterotoxigenic E. coli (ETEC)/rotavirus superinfection in PIE cells was developed. Cells were more susceptible to rotavirus infection when the challenge occurred in conjunction with ETEC compared to the virus alone. However, L. salivarius FFIG35 and FFIG58 maintained their ability to enhance IFN-β, IFN-λ and antiviral factors expression in PIE cells, and to reduce rotavirus replication in the context of superinfection. We also demonstrated that FFIG35 and FFIG58 strains regulated the immune response of PIE cells to rotavirus challenge or ETEC/rotavirus superinfection through the modulation of negative regulators of the TLR signaling pathway. In vivo studies performed in mice models confirmed the ability of L. salivarius FFIG58 to beneficially modulate the innate immune response and protect against ETEC infection. The results of this work contribute to the understanding of beneficial lactobacilli interactions with epithelial cells and allow us to hypothesize that the FFIG35 or FFIG58 strains could be used for the development of highly efficient functional feed to improve immune health status and reduce the severity of intestinal infections and superinfections in weaned piglets.
Report of the Pathogenesis and Pathophysiology of Lyme Disease Subcommittee of the HHS Tick Borne Disease Working Group

An understanding of the pathogenesis and pathophysiology of Lyme disease is key to the ultimate care of patients with Lyme disease. To better understand the various mechanisms underlying the infection caused by Borrelia burgdorferi, the Pathogenesis and Pathophysiology of Lyme Disease Subcommittee was formed to review what is currently known about the pathogenesis and pathophysiology of Lyme disease, from its inception, but also especially about its ability to persist in the host. To that end, the authors of this report were assembled to update our knowledge about the infectious process, identify the gaps that exist in our understanding of the process, and provide recommendations as to how to best approach solutions that could lead to a better means to manage patients with persistent Lyme disease.
Plant Small RNA World Growing Bigger: tRNA-Derived Fragments, Longstanding Players in Regulatory Processes

In the past 2 decades, the discovery of a new class of small RNAs, known as tRNA-derived fragments (tRFs), shed light on a new layer of regulation implicated in many biological processes. tRFs originate from mature tRNAs and are classified according to the tRNA regions that they derive from, namely 3′tRF, 5′tRF, and tRF-halves. Additionally, another tRF subgroup deriving from tRNA precursors has been reported, the 3′U tRFs. tRF length ranges from 17 to 26 nt for the 3′and 5′tRFs, and from 30 to 40 nt for tRF-halves. tRF biogenesis is still not yet elucidated, although there is strong evidence that Dicer (and DICER-LIKE) proteins, as well as other RNases such as Angiogenin in mammal and RNS proteins family in plants, are responsible for processing specific tRFs. In plants, the abundance of those molecules varies among tissues, developmental stages, and environmental conditions. More recently, several studies have contributed to elucidate the role that these intriguing molecules may play in all organisms. Among the recent discoveries, tRFs were found to be involved in distinctive regulatory layers, such as transcription and translation regulation, RNA degradation, ribosome biogenesis, stress response, regulatory signaling in plant nodulation, and genome protection against transposable elements. Although tRF biology is still poorly understood, the field has blossomed in the past few years, and this review summarizes the most recent developments in the tRF field in plants.
The Effect of a Modified GH11 Xylanase on Live Performance, Gut Health, and Clostridium perfringens Excretion of Broilers Fed Corn-Soy Diets

Xylanase enzymes and other feed additives are being used more commonly in poultry feed to reduce feed cost, improve performance, and maintain gut health. Five corn-soy-based dietary treatments were designed to compare the effect of different inclusion levels of high-efficiency GH11 xylanase on live performance, gut lesions, and Clostridium perfringens excretion in littler samples of broiler chickens. Diets were the standard diet (positive control; PC); a diet of reduced energy by 130 kcal/kg diet (negative control; NC); NC with xylanase at 10 XU/g of feed (NC + 10); NC with xylanase at 12.5 XU/g of feed (NC + 12.5); NC with xylanase at 15 XU/g of feed (NC + 15). Data were analyzed with one-way ANOVA. At 42 d, birds fed NC + 12.5 and NC + 15 were heavier (P < 0.05) than NC and comparable improvement to birds fed PC. Significant Improvement in FCR (P = 0.0001) was observed from 1 to 42 d for NC + 12.5 and NC + 15 compared with NC. Supplementation of xylanase reduced (P < 0.005) 21 d intestinal lesion score at 21 d with further improvement (P < 0.0001) at 42 d. NC + 15 reduced lesion scores by 24% compared with NC. Xylanase supplementations reduced litter C. perfringens cell forming unit per gram (CFU/g) compared with NC with the highest reduction of NC + 15 treatment by ~27%. In conclusion, xylanase can be included in reduced-energy diets up to 15 XU/g of feed to improve live performance, energy digestibility, and reduce intestinal lesion scores in broilers.
B Cell Metabolism and Autophagy in Autoimmunity

B cells are central to the pathogenesis of multiple autoimmune diseases, through antigen presentation, cytokine secretion, and the production of autoantibodies. During development and differentiation, B cells undergo drastic changes in their physiology. It is emerging that these are accompanied by equally significant shifts in metabolic phenotype, which may themselves also drive and enforce the functional properties of the cell. The dysfunction of B cells during autoimmunity is characterised by the breaching of tolerogenic checkpoints, and there is developing evidence that the metabolic state of B cells may contribute to this. Determining the metabolic phenotype of B cells in autoimmunity is an area of active study, and is important because intervention by metabolism-altering therapeutic approaches may represent an attractive treatment target.
Perioperative Sleep Disorder: A Review

Patients in the perioperative period usually present with different types and degrees of sleep disorders, which can severely affect their post-operative outcomes. Multiple risk factors may lead to the occurrence of perioperative sleep disorders, including personal factors, psychological factors, surgery factors, and environmental factors. In this review, we summarize the potential risk factors for perioperative sleep disorders during hospitalization. And it also provides an overview of perioperative outcomes and potential therapeutic prevention of perioperative sleep disorders. However, the further search is necessary to investigate the effectiveness and safety of preventions in the clinical practice and push forward the therapies.
Impaired DNA Repair Fidelity in a Breast Cancer Patient With Adverse Reactions to Radiotherapy

We tested the hypothesis that differences in DNA double-strand break (DSB) repair fidelity underlies differences in individual radiosensitivity and, consequently, normal tissue reactions to radiotherapy. Fibroblast cultures derived from a radio-sensitive (RS) breast cancer patient with grade 3 adverse reactions to radiotherapy were compared with normal control (NC) and hyper-radiosensitive ataxia-telangiectasia mutated (ATM) cells. DSB repair and repair fidelity were studied by Southern blotting and hybridization to Alu repetitive sequence and to a specific 3.2-Mbp NotI restriction fragment on chromosome 21, respectively. Results for DNA repair kinetics using the NotI fidelity assay showed significant differences (P < 0.001) with higher levels of misrepaired (misrejoined and unrejoined) DSBs in RS and ATM compared with NC. At 24-h postradiation, the relative fractions of misrepaired DSBs were 10.64, 23.08, and 44.70% for NC, RS, and ATM, respectively. The Alu assay showed significant (P < 0.05) differences in unrepaired DSBs only between the ATM and both NC and RS at the time points of 12 and 24 h. At 24 h, the relative percentages of DSBs unrepaired were 1.33, 3.43, and 12.13% for NC, RS, and ATM, respectively. The comparison between the two assays indicated an average of 5-fold higher fractions of misrepaired (NotI assay) than unrepaired (Alu assay) DSBs. In conclusion, this patient with increased radiotoxicity displayed more prominent misrepaired than unrepaired DSBs, suggesting that DNA repair fidelity is a potential marker for the adverse reactions to radiotherapy. More studies are required to confirm these results and further develop DSB repair fidelity as a hallmark biomarker for interindividual differences in radiosensitivity.
Neddylation Regulates Macrophages and Implications for Cancer Therapy

Tumor-associated macrophages (TAMs) promote cancer progression via stimulating angiogenesis, invasion/metastasis, and suppressing anti-cancer immunity. Targeting TAMs is a potential promising cancer therapeutic strategy. Neddylation adds the ubiquitin-like protein NEDD8 to substrates, and thereby regulates diverse biological processes in multiple cell types, including macrophages. By controlling cellular responses, the neddylation pathway regulates the function, migration, survival, and polarization of macrophages. In the present review we summarized how the neddylation pathway modulates Macrophages and its implications for cancer therapy.
Living up to the Hype of Hyperspectral Aquatic Remote Sensing: Science, Resources and Outlook

Intensifying pressure on global aquatic resources and services due to population growth and climate change is inspiring new surveying technologies to provide science-based information in support of management and policy strategies. One area of rapid development is hyperspectral remote sensing: imaging across the full spectrum of visible and infrared light. Hyperspectral imagery contains more environmentally meaningful information than panchromatic or multispectral imagery and is poised to provide new applications relevant to society, including assessments of aquatic biodiversity, habitats, water quality, and natural and anthropogenic hazards. To aid in these advances, we provide resources relevant to hyperspectral remote sensing in terms of providing the latest reviews, databases, and software available for practitioners in the field. We highlight recent advances in sensor design, modes of deployment, and image analysis techniques that are becoming more widely available to environmental researchers and resource managers alike. Systems recently deployed on space- and airborne platforms are presented, as well as future missions and advances in unoccupied aerial systems (UAS) and autonomous in-water survey methods. These systems will greatly enhance the ability to collect interdisciplinary observations on-demand and in previously inaccessible environments. Looking forward, advances in sensor miniaturization are discussed alongside the incorporation of citizen science, moving toward open and FAIR (findable, accessible, interoperable, and reusable) data. Advances in machine learning and cloud computing allow for exploitation of the full electromagnetic spectrum, and better bridging across the larger scientific community that also includes biogeochemical modelers and climate scientists. These advances will place sophisticated remote sensing capabilities into the hands of individual users and provide on-demand imagery tailored to research and management requirements, as well as provide critical input to marine and climate forecasting systems. The next decade of hyperspectral aquatic remote sensing is on the cusp of revolutionizing the way we assess and monitor aquatic environments and detect changes relevant to global communities.
A Protective Role of FAM13A in Human Airway Epithelial Cells Upon Exposure to Cigarette Smoke Extract

Background Chronic Obstructive Pulmonary Disease (COPD) is a progressive lung disease characterized by chronic inflammation upon inhalation of noxious particles, e.g., cigarette smoke. FAM13A is one of the genes often found to be associated with COPD, however its function in the pathophysiology of COPD is incompletely understood. We studied its role in airway epithelial barrier integrity and cigarette smoke-induced epithelial responses. Materials and Methods Protein level and localization of FAM13A was assessed with immunohistochemistry in lung tissue from COPD patients and non-COPD controls. In vitro, FAM13A expression was determined in the absence or presence of cigarette smoke extract (CSE) in primary airway epithelial cells (AECs) from COPD patients and controls by western blotting. FAM13A was overexpressed in cell line 16HBE14o- and its effect on barrier function was monitored real-time by electrical resistance. Expression of junctional protein E-cadherin and β-catenin was assessed by western blotting. The secretion of neutrophil attractant CXCL8 upon CSE exposure was measured by ELISA. Results FAM13A was strongly expressed in airway epithelium, but significantly weaker in airways of COPD patients compared to non-COPD controls. In COPD-derived AECs, but not those of controls, FAM13A was significantly downregulated by CSE. 16HBE14o- cells overexpressing FAM13A built up epithelial resistance significantly more rapidly, which was accompanied by higher E-cadherin expression and reduced CSE-induced CXCL8 levels. Conclusion Our data indicate that the expression of FAM13A is lower in airway epithelium of COPD patients compared to non-COPD controls. In addition, cigarette smoking selectively downregulates airway epithelial expression of FAM13A in COPD patients. This may have important consequences for the pathophysiology of COPD, as the more rapid build-up of epithelial resistance upon FAM13A overexpression suggests improved (re)constitution of barrier function. The reduced epithelial secretion of CXCL8 upon CSE-induced damage suggests that lower FAM13A expression upon cigarette smoking may facilitate epithelial-driven neutrophilia.
Spiking Neural Network for Fourier Transform and Object Detection for Automotive Radar

The development of advanced autonomous driving applications is hindered by the complex temporal structure of sensory data, as well as by the limited computational and energy resources of their on-board systems. Currently, neuromorphic engineering is a rapidly growing field that aims to design information processing systems similar to the human brain by leveraging novel algorithms based on spiking neural networks (SNNs). These systems are well-suited to recognize temporal patterns in data while maintaining a low energy consumption and offering highly parallel architectures for fast computation. However, the lack of effective algorithms for SNNs impedes their wide usage in mobile robot applications. This paper addresses the problem of radar signal processing by introducing a novel SNN that substitutes the discrete Fourier transform and constant false-alarm rate algorithm for raw radar data, where the weights and architecture of the SNN are derived from the original algorithms. We demonstrate that our proposed SNN can achieve competitive results compared to that of the original algorithms in simulated driving scenarios while retaining its spike-based nature.
Effects of Male Age and Female Presence on Male Associations in a Large, Polygynous Mammal in Southern India: The Asian Elephant

We present a detailed study of male associations in the Asian elephant, using 6 years of data on identified, non-musth males. Adult males spent greater proportions of their time solitarily than in mixed-sex or in all-male groups. Old (over 30 years) males were sighted more frequently with their age-peers and less frequently with young (15–30 years) males than expected at random in all-male groups. Young males were not sighted more frequently with old males than with young males, and did not disproportionately initiate associations with old males. These results suggest that male associations, in the absence of females, may allow for old non-musth males to test strengths against age-peers. Social learning from older individuals did not seem to be important in male associations, unlike that observed in the African savannah elephant. We also found a constraint on the sizes of all-male groups, similar to that seen in female groups in our study population, and all-male groups were rarer and smaller than those in African savannah elephant. Although male associations were weak, most males had a significant top associate, with whom their association was the strongest, in female absence. In mixed-sex groups, male associations occurred at random, suggesting that males were tracking female groups independently. Differences in male social organization from that of the related African savannah elephant that occupies a similar niche possibly arise from differences in ecology.
Presence of Left Atrial Fibrosis May Contribute to Aberrant Hemodynamics and Increased Risk of Stroke in Atrial Fibrillation Patients

Atrial fibrillation (AF) patients are at high risk of stroke, with the left atrial appendage (LAA) found to be the most common site of clot formation. Presence of left atrial (LA) fibrosis has also been associated with higher stroke risk. However, the mechanisms for increased stroke risk in patients with atrial fibrotic remodeling are poorly understood. We sought to explore these mechanisms using fluid dynamic analysis and to test the hypothesis that the presence of LA fibrosis leads to aberrant hemodynamics in the LA, contributing to increased stroke risk in AF patients. We retrospectively collected late-gadolinium-enhanced MRI (LGE-MRI) images of eight AF patients (four persistent and four paroxysmal) and reconstructed their 3D LA surfaces. Personalized computational fluid dynamic simulations were performed, and hemodynamics at the LA wall were quantified by wall shear stress (WSS, friction of blood), oscillatory shear index (OSI, temporal directional change of WSS), endothelial cell activation potential (ECAP, ratio of OSI and WSS), and relative residence time (RRT, residence time of blood near the LA wall). For each case, these hemodynamic metrics were compared between fibrotic and non-fibrotic portions of the wall. Our results showed that WSS was lower, and OSI, ECAP, and RRT was higher in the fibrotic region as compared to the non-fibrotic region, with ECAP (p = 0.001) and RRT (p = 0.002) having significant differences. Case-wise analysis showed that these differences in hemodynamics were statistically significant for seven cases. Furthermore, patients with higher fibrotic burden were exposed to larger regions of high ECAP, which represents regions of low WSS and high OSI. Consistently, high ECAP in the vicinity of the fibrotic wall suggest that local blood flow was slow and oscillating that represents aberrant hemodynamic conditions, thus enabling prothrombotic conditions for circulating blood. AF patients with high LA fibrotic burden had more prothrombotic regions, providing more sites for potential clot formation, thus increasing their risk of stroke.
Methyl-Donor Micronutrient for Gestating Sows: Effects on Gut Microbiota and Metabolome in Offspring Piglets

This study aimed to investigate the effects of maternal methyl-donor micronutrient supplementation during gestation on gut microbiota and the fecal metabolic profile in offspring piglets. Forty-three Duroc × Erhualian gilts were assigned to two dietary groups during gestation: control diet (CON) and CON diet supplemented with MET (folic acid, methionine, choline, vitamin B6, and vitamin B12). The body weights of offspring piglets were recorded at birth and weaning. Besides this, fresh fecal samples of offspring piglets were collected at 7, 14, and 21 days. The gut microbiota composition, metabolic profile, and short-chain fatty acid (SCFA) profiles in the fecal samples were determined using 16S rDNA sequencing, liquid chromatography-mass spectrometry metabolomics, and gas chromatography methods, respectively. The results showed that maternal methyl-donor micronutrient supplementation increased the microbiota diversity and uniformity in feces of offspring piglets as indicated by increased Shannon and Simpson indices at 7 days, and greater Simpson, ACE, Chao1 and observed species indices at 21 days. Specifically, at the phylum level, the relative abundance of Firmicutes and the Firmicutes to Bacteroidetes ratio were elevated by maternal treatment. At the genus level, the relative abundance of SCFA-producing Dialister, Megasphaera, and Turicibacter, and lactate-producing Sharpea as well as Akkermansia, Weissella, and Pediococcus were increased in the MET group. The metabolic analyses show that maternal methyl-donor micronutrient addition increased the concentrations of individual and total SCFAs of 21-day piglets and increased metabolism mainly involving amino acids, pyrimidine, and purine biosynthesis. Collectively, maternal methyl-donor micronutrient addition altered gut microbiota and the fecal metabolic profile, resulting in an improved weaning weight of offspring piglets.