Miracle-dz/UniFAR-FTUs huggingface dataset:
The Histone Variant MacroH2A1 Regulates Key Genes for Myogenic Cell Fusion in a Splice-Isoform Dependent Manner

MacroH2A histone variants have functions in differentiation, somatic cell reprogramming and cancer. However, at present, it is not clear how macroH2As affect gene regulation to exert these functions. We have parted from the initial observation that loss of total macroH2A1 led to a change in the morphology of murine myotubes differentiated ex vivo. The fusion of myoblasts to myotubes is a key process in embryonic myogenesis and highly relevant for muscle regeneration after acute or chronic injury. We have focused on this physiological process, to investigate the functions of the two splice isoforms of macroH2A1. Individual perturbation of the two isoforms in myotubes forming in vitro from myogenic C2C12 cells showed an opposing phenotype, with macroH2A1.1 enhancing, and macroH2A1.2 reducing, fusion. Differential regulation of a subset of fusion-related genes encoding components of the extracellular matrix and cell surface receptors for adhesion correlated with these phenotypes. We describe, for the first time, splice isoform-specific phenotypes for the histone variant macroH2A1 in a physiologic process and provide evidence for a novel underlying molecular mechanism of gene regulation.
The biosynthesis of exo- and cell wall-polysaccharides is sensitive to brefeldin A in the cyanobacterium Leptolyngbya VRUC 135

Inhibitory effects of brefeldin A (BFA) on the functioning of secretory systems has been extensively investigated in eukaryotic cells. In this study we report, for the first time, the in vivo effect of 50 and 100 μg ml – 1 BFA on the biosynthesis of exo- and cell wall-polysaccharides in the cyanobacterium, Leptolyngbya VRUC 135, isolated from Roman hypogea (archaeological underground chambers). The drug inhibited the synthesis and the translocation of both exo- and cell wall-polysaccharides. This inhibitory effect could be due to direct or indirect alterations in membrane organization and, consequently, membrane function.
Association of Childhood Trauma Exposure with Inflammatory Biomarkers Among Midlife Women.

Background: Childhood abuse has been associated with poor health outcomes in adulthood. However, the physiologic pathways by which abuse is linked to health are not fully elucidated. Inflammation plays a significant role in the pathophysiology of multiple chronic diseases. We tested whether childhood trauma exposure was related to increased systemic inflammation in midlife women. Materials and Methods: Participants were 304 nonsmoking perimenopausal and postmenopausal women aged 40 to 60 years and free of cardiovascular disease. They completed questionnaires assessing psychosocial and behavioral factors, including childhood trauma, anthropometric measures, wrist actigraphy sleep measurements, and a fasting blood draw for inflammatory markers high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). Associations between childhood trauma and inflammatory markers were tested in linear regression models controlling for age, race/ethnicity, education, body mass index, anti-inflammatory medication use, and alcohol consumption. Other covariates considered included sleep continuity and depressive symptoms. Results: A total of 44.8% of the sample experienced at least one type of childhood abuse/neglect. Women with a history of emotional abuse had higher IL-6 levels than women without this history in multivariate models (β = 0.077, standard error = 0.032, p = 0.017). Results were not accounted for by covariates and persisted additionally controlling for depressive symptoms and sleep. Childhood abuse/neglect was not related to hsCRP. Conclusions: Childhood emotional abuse was associated with higher levels of IL-6 in midlife women. Assessing childhood trauma exposure along with inflammatory markers may be important for the development of prevention strategies at midlife to prevent chronic diseases later in life.
Genetic Markers in S. Paratyphi C Reveal Primary Adaptation to Pigs

Salmonella enterica with the identical antigenic formula 6,7:c:1,5 can be differentiated biochemically and by disease syndrome. One grouping, Salmonella Paratyphi C, is currently considered a typhoidal serovar, responsible for enteric fever in humans. The human-restricted typhoidal serovars (S. Typhi and Paratyphi A, B and C) typically display high levels of genome degradation and are cited as an example of convergent evolution for host adaptation in humans. However, S. Paratyphi C presents a different clinical picture to S. Typhi/Paratyphi A, in a patient group with predisposition, raising the possibility that its natural history is different, and that infection is invasive salmonellosis rather than enteric fever. Using whole genome sequencing and metabolic pathway analysis, we compared the genomes of 17 S. Paratyphi C strains to other members of the 6,7:c:1,5 group and to two typhoidal serovars: S. Typhi and Paratyphi A. The genome degradation observed in S. Paratyphi C was much lower than S. Typhi/Paratyphi A, but similar to the other 6,7:c:1,5 strains. Genomic and metabolic comparisons revealed little to no overlap between S. Paratyphi C and the other typhoidal serovars, arguing against convergent evolution and instead providing evidence of a primary adaptation to pigs in accordance with the 6,7:c:1.5 strains.
Potent Inhibitory Effect of BJ-3105, a 6-Alkoxypyridin-3-ol Derivative, on Murine Colitis Is Mediated by Activating AMPK and Inhibiting NOX

Inflammatory bowel disease (IBD) is a chronic relapsing inflammation in the gastrointestinal tract. Biological therapeutics and orally available small molecules like tofacitinib (a JAK inhibitor) have been developed to treat IBD, but half of the patients treated with these drugs fail to achieve sustained remission. In the present study, we compared the therapeutic effects of BJ-3105 (a 6-alkoxypyridin-3-ol derivative) and tofacitinib in IBD. BJ-3105 induced activation of AMP-activated protein kinase (AMPK) in the kinase activity measurement and recovery from cytokine-induced AMPK deactivation in HT-29 human colonic epithelial cells. Similar to tofacitinib and D942 (an AMPK activator), BJ-3105 inhibited IL-6-induced JAK2/STAT3 phosphorylation and TNF-α-stimulated activation of IKK/NF-κB, and consequently, stimulus-induced upregulations of inflammatory cytokines and inflammasome components. In addition, unlike tofacitinib or D942, BJ-3105 inhibited NADPH oxidase (NOX) activation and consequent superoxide production induced by activators (mevalonate and geranylgeranyl pyrophosphate) of the NOX cytosolic component Rac. In mice, oral administration with BJ-3105 ameliorated dextran sulfate sodium (DSS)-induced colitis and azoxymethane/DSS-induced colitis-associated tumor formation (CAT) much more potently than that with tofacitinib. Moreover, BJ-3105 suppressed the more severe form of colitis and CAT formation in mice with AMPK knocked-out in macrophages (AMPKαfl/fl-Lyz2-Cre mice) with much greater efficacy than tofacitinib. Taken together, our findings suggest BJ-3105, which exerted a much better anti-colitis effect than tofacitinib through AMPK activation and NOX inhibition, is a promising candidate for the treatment of IBD.
Limited Proteolysis of Cyclooxygenase-2 Enhances Cell Proliferation

Accumulating evidence suggests that the cyclooxygenase-2 (COX-2) enzyme has additional catalytic-independent functions. Here we show that COX-2 appears to be cleaved in mouse and human tumors, which led us to hypothesize that COX-2 proteolysis may play a role in cell proliferation. The data presented herein show that a K598R point mutation at the carboxyl-terminus of COX-2 causes the appearance of several COX-2 immunoreactive fragments in nuclear compartments, and significantly enhances cell proliferation. In contrast, insertion of additional mutations at the border of the membrane-binding and catalytic domains of K598R COX-2 blocks fragment formation and prevents the increase in proliferation. Transcriptomic analyses show that K598R COX-2 significantly affects the expression of genes involved in RNA metabolism, and subsequent proteomics suggest that it is associated with proteins that regulate mRNA processing. We observe a similar increase in proliferation by expressing just that catalytic domain of COX-2 (ΔNT- COX-2), which is completely devoid of catalytic activity in the absence of its other domains. Moreover, we show that the ΔNT- COX-2 protein also interacts in the nucleus with β-catenin, a central regulator of gene transcription. Together these data suggest that the cleavage products of COX-2 can affect cell proliferation by mechanisms that are independent of prostaglandin synthesis.
Isolation of novel bovine parainfluenza virus type 5 (bPIV5) and its incidence in Korean cattle

Abstract : Four viruses showing cytopathic effects in MDBK cells were isolated from brains of cattle showing downercattle syndrome in 2012. The isolates were confirmed to belong to the genus Rubulavirus of the subfamilyParamyxovirinae. Isolate QIA-B1201 had the ability to hemagglutinate red blood cells from several species of animalsand was capable of adsorbing guinea pig erythrocytes on the surface of infected Vero cells. Nucleotide sequence analysisshowed that two isolates (QIA-B1201 and QIA-B1204) had high similarity with other human and animal PIV5 isolatesranging from 98.1 to 99.8%. The highest sequence similarity of the two isolates corresponded to strain KNU-11 (99.8%at the nucleotide and amino acid level) isolated from suckling piglets in Korea in 2012. To evaluate the virulenceof strain QIA-B1201, we inoculated bPIV5 into 5 week-old mice via both the intraperitoneal and intracranial route.Body weight was not significantly altered in mice inoculated with QIA-B1201. In this study, we isolated andcharacterized novel bPIV5s from brain samples showing downer cattle syndrome, but were not able to elucidate thepathogenicity of the bPIV5s in mice.Keywords : bovine, neurologic disease, parainfluenza virus 5, virus isolation
Variable Thickness in Plates—A Solution for SHM Based on the Topological Derivative

The topological derivative tool is applied here in structural health monitoring (SHM) problems to locate small defects in a material plate with complex geometry that is subject to permanent multifrequency guided waves excitation. Compared to more standard SHM methods, based in measuring the time-lag between emitted and received propagative pulses plus some postprocessing, the topological derivative somehow compares the measured and computed (solving the full elasto-dynamic equations) response of the damaged plate, instead of relying on only the time of flight of the wave. Thus, the method profits the knowledge behind the physics of the problem and can cope with scenarios in which classical methods give poor results. The authors of this paper have already used the topological derivative in rectangular plates with constant thickness, but with defects consisting simply in both through slits and inclusions of a different material, and actuators/sensors located near the boundary, which makes very difficult to use standard SHM methods. This is an extension of the method, also considering the much more difficult to analyze case of plates with variable thickness and complex (non-rectangular) planform.
Pain Diagnosis, Pain Coping, and Function in Individuals with Chronic Musculoskeletal Pain

Purpose Research supports a role for coping responses in adjustment to chronic pain. However, it is likely that some coping responses play a larger role in adjustment to pain for some individuals than others. The identification of the factors that moderate the association between coping responses and pain-related outcomes has important clinical implications. This study sought to determine if musculoskeletal pain diagnosis moderates the associations between eight pain-coping responses and both pain and function. Patients and Methods A non-probabilistic sample of 323 persons with different chronic musculoskeletal pain conditions completed measures of pain intensity, physical function, psychological function, and pain-coping responses. Results With only one exception, the frequency of use of pain-coping responses was not associated with pain diagnosis. Statistically significant moderation effects of pain diagnosis on the association between coping and pain outcomes were found for two coping responses: 1) support seeking when predicting pain intensity, and 2) resting when predicting both physical and psychological function. Conclusion The findings indicate that coping responses tend to play a similar role in patients' pain and function across different musculoskeletal pain conditions, with some important exceptions. If the findings are found to replicate in other samples, they would have important implications for determining when psychosocial pain treatments might (and when they might not) need to be adapted for specific diagnostic groups.
Glaucomatous Progression After Lens Extraction in Primary Angle Closure Disease Spectrum

Precis: Substantial proportion of primary angle closure glaucoma (PACG) eyes showed glaucomatous worsening after successful lens extraction and intraocular pressure (IOP) control, which may suggest that an earlier intervention may be required to prevent PACG. Purpose: The purpose of this study was to investigate the longitudinal clinical course of the primary angle closure (PAC) disease spectrum, including PAC, primary angle closure suspect (PACS), and PACG patients, who underwent lens extraction. Methods: This retrospective observational study included 77 eyes from patients with PACS, PAC, and PACG who underwent lens extraction and were followed up for >2 years after surgery. The mean, peak, and fluctuation of IOP were analyzed before and after lens extraction among groups. Visual field (VF) mean deviation was compared immediately after lens extraction and the final follow-up. Postoperative glaucoma progression determined by 3 criteria (optic disc/retinal nerve fiber layer photographs, optical coherent tomography, and VF) was compared among the 3 groups. Results: Seventeen PACS, 24 PAC, and 36 PACG eyes were included. The mean and peak IOP, and IOP fluctuation IOP were significantly reduced postoperatively in all groups. Postoperative VF mean deviation was significantly aggravated only in the PACG group (from −7.26 to −8.82 dB, P<0.001). The prevalence of postoperative glaucoma progression by at least 1 criterion was significantly higher in PACG, and none of the eyes with PACS and PAC showed VF conversion (PACS, PAC, PACG; 11.8%, 12.5% vs. 61.1% in disc/retinal nerve fiber layer, 11.8%, 8.3% vs. 63.9% in optical coherent tomography, 0%, 0% vs. 33.3% in VF, all P<0.001). Conclusions: In the PAC spectrum, lens extraction achieved significant IOP reduction. However, despite IOP control, a substantial proportion of PACG eyes showed glaucomatous progression. This result may suggest that lens extraction should be performed early to prevent PACG.
Altered tibiofemoral position following ACL reconstruction is associated with cartilage matrix changes: A voxel‐based relaxometry analysis

The purpose of this study was to analyze the relationship between postsurgical tibial translation (TT) and tibial rotation (TR) with cartilage matrix changes using quantitative magnetic resonance imaging, specifically voxel‐based relaxometry with T1ρ and T2 mapping sequences. Knee magnetic resonance imaging's (MRI's) of 51 patients with unilateral anterior cruciate ligament injury, no concomitant ligamentous injury, history of osteoarthritis (OA), and previous knee surgery were scanned prior to surgery. Thirty‐four patients completed follow‐up MRI scans at 6‐month, 1‐ and 2‐year post‐reconstruction and were included in this study. Knee biomechanics, T1ρ, and T2 were calculated using an in‐house Matlab program. Compared to the contralateral knee, the injured knee demonstrated significantly increased anterior TT at baseline (P < .001), 6‐month (P < .001), 1‐ (P = .001), and 2‐year (P < .001). Furthermore, patients were divided into groups based on TT at 6‐month. When compared to patients with normal TT, those with increased anterior TT at 6‐month displayed significantly longer T1ρ and T2 relaxation times in 10.4% and 7.4% of the voxels in the injured medial tibia at 1‐year, respectively, as well as 12.4% and 9.8% of the voxels in the injured medial tibia at 2‐year, respectively. Our results demonstrate an association between abnormal tibiofemoral position and early degradative changes to the articular cartilage matrix of the injured knee. Clinical significance: These findings suggest that altered tibiofemoral position following ACL reconstruction is associated with early degeneration of knee cartilage. Future prospective studies employing longer follow‐up times are warranted to evaluate the relationship between abnormal tibiofemoral position and the early onset of posttraumatic OA.
Crosstalk Analysis of a CMOS Single Membrane Thermopile Detector Array

We present a new experimental technique to characterise the crosstalk of a thermopile-based thermal imager, based on bi-directional electrical heating of thermopile elements. The new technique provides a significantly simpler and more reliable method to determine the crosstalk, compared to a more complex experimental setup with a laser source. The technique is used to characterise a novel single-chip array, fabricated on a single dielectric membrane. We propose a theoretical model to simulate the crosstalk, which shows good agreement with the experimental results. Our results allow a better understanding of the thermal effects in these devices, which are at the center of a rising market of industrial and consumer applications.
Sleep apnoea management in Europe during the COVID-19 pandemic: data from the European Sleep Apnoea Database (ESADA)

Sleep disordered breathing (SDB) is highly prevalent, with a male to female predominance of two to one, and is more common in middle-aged and elderly subjects [1]. Affected patients often present with comorbidities such as obesity, cardiovascular disease (systemic hypertension, heart failure, atrial fibrillation) and diabetes mellitus type II [2]. The strong overlap between the profile for SDB patients and the identified risk factors for adverse outcomes of coronavirus disease 2019 (COVID-19) infection, which include age, male sex and cardiometabolic comorbidity [3], suggest that SDB patients may benefit from effective therapy if confronted with COVID-19 infection [4]. This study identified an 80% shutdown of sleep apnoea management throughout Europe. Most services have been limited to phone-based follow-up and the management of high-priority cases. Mitigation strategies appear to be insufficiently exploited. https://bit.ly/2KWf3IY
Common and Unique Factors and the Bidirectional Relationship Between Chronic Kidney Disease and Nonalcoholic Fatty Liver in Type 2 Diabetes Patients

Purpose This study aimed to investigate the common and unique risk factors and bidirectional relationship between chronic kidney disease (CKD) and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Patients and Methods This was a cross-sectional study of patients with T2DM enrolled in a disease management program at two specialized diabetes outpatient clinics. Common and unique risk factors for CKD and NAFLD were examined using structural equation models (SEMs). SEMs were also used to examine direct and indirect effects of NAFLD on CKD and those of CKD on NAFLD. Results A total of 1992 subjects with T2DM were enrolled in this study. In multivariate analysis, NAFLD was independently associated with the odds of CKD (adjusted odds ratio=1.59, 95% confidence interval=1.12–2.25, P=0.009). SEMs showed that age, triglyceride, uric acid (UA), albumin, and HbA1c levels had statistically significant direct effects on CKD, and the final model could explain 22% of the variability in CKD. Age, triglycerides, body mass index (BMI), UA, white blood cell (WBC) count, serum glutamic pyruvic transaminase (SGPT) level, and smoking status had statistically significant direct effects on NAFLD, and the final model could explain 43% of the variability in NAFLD. The common risk factors contributing to both CKD and NAFLD were age, triglycerides, and UA. The unique risk factors were albumin and HbA1c for CKD, and BMI, WBC, SGPT, and smoking for NAFLD. In addition, SEM analysis also confirmed the bidirectional causal relationship between NAFLD and CKD. Conclusion Common and unique risk factors and a bidirectional relationship existed between CKD and NAFLD in our patients with T2DM.
Logical Characterisation of Hybrid Conformance

Logical characterisation of a behavioural equivalence relation precisely specifies the set of formulae that are preserved and reflected by the relation. Such characterisations have been studied extensively for exact semantics on discrete models such as bisimulations for labelled transition systems and Kripke structures, but to a much lesser extent for approximate relations, in particular in the context of hybrid systems. We present what is to our knowledge the first characterisation result for approximate notions of hybrid refinement and hybrid conformance involving tolerance thresholds in both time and value. Since the notion of conformance in this setting is approximate, any characterisation will unavoidably involve a notion of relaxation, denoting how the specification formulae should be relaxed in order to hold for the implementation. We also show that an existing relaxation scheme on Metric Temporal Logic used for preservation results in this setting is not tight enough for providing a characterisation of neither hybrid conformance nor refinement. The characterisation result, while interesting in its own right, paves the way to more applied research, as our notion of hybrid conformance underlies a formal model-based technique for the verification of cyber-physical systems.
Economic psychology

In early 2020, the novel coronavirus (COVID-19) spread to the United States and upended normal life. Using trip-level data on over 17 million taxi rides taken in Chicago from 2018– 2021, I document how tipping behavior changed during the COVID-19 pandemic. I find that the average non-zero tip as a percent of the taxi fare increased 2 percentage points, or roughly 10%. Meanwhile, the likelihood that a passenger left a tip at all declined by roughly 5 percentage points, down from a pre-pandemic likelihood of 95%. My preferred specification suggests that the effect on the intensive margin dominates that in the extensive margin, leading to an aggregate increase in tipping generosity during the pandemic. I leverage granularity in the data to explore the mechanisms behind these trends and offer two explanations consistent with the data. First, passengers responded to the major economic shocks of the pandemic – unemployment and savings overhangs – by varying their tipping rates accordingly. Second, passengers internalized the increased risk of COVID-19 infection as an additional cost for taxi drivers and increased their tips as compensation. My analysis testifies to the sustainability of tipping in times of crises and offers theoretical insight into what drives tipping behavior.
Effects of Enzymatic Treatment of Corn Gluten Meal on Lutein and Zeaxanthin Extraction

The effects of enzymatic treatment of corn gluten on the extraction of lutein and zeaxanthin (non-provitamin A carotenoids), which have multiple bio-functional properties in human beings, were studied. They were extracted from corn gluten meal (CGM) after pretreatment by protease (neutrase 0.5 L) under the following conditions: enzyme content 214 (U/g protein), solid content 15%, and hydrolysis time of 2 h. The yields of crude lutein, crude zeaxanthin, and total carotenoids were increased from 74.1, 77.1, and 393.6 to 113.5, 140.1, and 599.1 (µg/g, CGM on moisture-free basis), respectively.