Miracle-dz/UniFAR-FTUs huggingface dataset:
Alterations of the brain proteome and gut microbiota in D-galactose-induced brain aging mice with krill oil supplementation.

Brain aging is commonly associated with neurodegenerative disorders, but the ameliorative effect of krill oil and the underlying mechanism remain unclear. In this study, the components of krill oil were measured, and the antiaging effects of krill oil were investigated in mice with D-galactose (D-gal)-induced brain aging via proteomics and gut microbiota analysis. Krill oil treatment decreased the expression of truncated dopamine- and cAMP-regulated phosphoproteins and proteins involved in the calcium signaling pathway. In addition, the concentrations of dopamine were increased in the serum (p<0.05) and brain (p>0.05) due to the enhanced expression of tyrosine-3-monooxygenase and aromatic L-amino acid decarboxylase. Moreover, krill oil alleviated gut microbiota dysbiosis, decreased the abundance of bacteria that consume the precursor tyrosine and increased the abundance of Lactobacillus spp. and short-chain fatty acid producers. This study revealed the beneficial effect of krill oil against D-gal-induced brain aging and clarified the underlying mechanism through proteomics and gut microbiota analysis.
Pulmonary Aptamer Signatures in Children's Interstitial and Diffuse Lung Diseases.

RATIONALE Biomarker signatures are needed in children with interstitial and diffuse lung disease (chILD) to improve diagnostic approaches, increase our understanding of disease pathogenesis, monitor disease progression, and develop new treatment strategies. Proteomic technology using SOMAmer® (Slow Off-rate Modified Aptamer) nucleic acid-based protein binding reagents allow for biomarker discovery. OBJECTIVES We hypothesized that proteins and protein pathways in bronchoalveolar lavage fluid (BALF) would distinguish children with neuroendocrine cell hyperplasia of infancy (NEHI), surfactant dysfunction mutations, other chILD diagnoses, and controls. METHODS BALF was collected for clinical indications and banked in patients with chILD and disease controls using standardized protocols over 10 years. BALF supernatant was analyzed using an aptamer assay to measure 1129 protein levels. Protein levels were compared between groups using an analysis of variance and adjusted for multiple comparisons using false discovery rate. Proteins were classified into pathways. Hierarchical clustering was used to define endotypes in the group of children with NEHI. RESULTS After correcting for multiple testing, children with NEHI (n=22) had 202 aptamers that were significantly different (p<0.05) in BALF compared to controls (n=9). Children with surfactant mutation (n=8) had 51 aptamers significantly different (p<0.05) in BALF compared to controls (n=9). Proteins associated with pulmonary fibrosis and inflammation were associated with the surfactant dysfunction group, but not in the NEHI group. Using hierarchical clustering analysis, two distinct NEHI endotypes were identified. CONCLUSIONS Distinct proteins and protein pathways can be determined from BALF of children with chILD, and these hold promise to further our understanding of chILD.
Meckel syndrome: Clinical and mutation profile in six fetuses

Meckel syndrome (MKS) is a perinatally lethal, genetically heterogeneous, autosomal recessive condition caused by defective primary cilium formation leading to polydactyly, multiple cysts in kidneys and malformations of nervous system. We performed exome sequencing in six fetuses from six unrelated families with MKS. We identified seven novel variants in B9D2, TNXDC15, CC2D2A, CEP290 and TMEM67. We describe the second family with MKS due to a homozygous variant in B9D2 and fifth family with bi‐allelic variant in TXNDC15. Our data validates the causation of MKS by pathogenic variation in B9D2 and TXNDC15 and also adds novel variants in CC2D2A, CEP290 and TMEM67 to the literature.
Development of a contrast‐enhanced micro computed tomography protocol for the oval squid (Sepioteuthis lessoniana) brain

Coleoid cephalopods (squid, cuttlefish, and octopus) have a well‐developed and complex central nervous system. Its absolute size is the largest among invertebrates, and the brain‐to‐body mass ratio is larger than that of fish and reptiles and equivalent to that of birds and mammals. Although a number of histological studies have been conducted on the brains of cephalopods, most of them used a light microscope or an electron microscope, which show the microstructure of the brain, but often cannot image the whole brain instantaneously. Of late, micro computed tomography (CT) has gained popularity for imaging animal brains because it allows for noninvasive three‐dimensional (3D) reconstruction and preprocessing that are not cumbersome. To perform micro‐CT on cephalopod brains, we first tested conditions suitable for preprocessing, paying special attention to staining conditions that would provide high contrast images. Four agents, iodine in 99.5% ethanol, iodine potassium iodide in water (IKI), phosphotungstic acid in 70% ethanol, and nonionic iodinated contrast agent in water, were tested at various concentrations and durations on brain of juvenile oval squid. To evaluate the quality of staining, we calculated the contrast ratio of the two‐dimensional (2D) images and compared 3D segmentation of the best and worst 2D images. We concluded that 3% IKI staining for 7 days was the best combination to enhance the images contrast of the oval squid brain, in which each brain lobe was clearly detected and 3D segmentation of the whole brain was possible. The wider applicability of this preprocessing method for micro‐CT of the brains of other cephalopods is discussed.
Assessment of the effect of continuous theta burst stimulation of the motor cortex on manual dexterity in non‐human primates in a direct comparison with invasive intracortical pharmacological inactivation

Non‐invasive reversible perturbation techniques of brain output such as continuous theta burst stimulation (cTBS), commonly used to modulate cortical excitability in humans, allow investigation of possible roles in functional recovery played by distinct intact cortical areas following stroke. To evaluate the potential of cTBS, the behavioural effects of this non‐invasive transient perturbation of the hand representation of the primary motor cortex (M1) in non‐human primates (two adult macaques) were compared with an invasive focal transient inactivation based on intracortical microinfusion of GABA‐A agonist muscimol. The effects on the contralateral arm produced by cTBS or muscimol were directly compared based on a manual dexterity task performed by the monkeys, the “reach and grasp” drawer task, allowing quantitative assessment of the grip force produced between the thumb and index finger and exerted on the drawer's knob. cTBS only induced modest to moderate behavioural effects, with substantial variability on manual dexterity whereas the intracortical muscimol microinfusion completely impaired manual dexterity, producing a strong and clear cortical inhibition of the M1 hand area. In contrast, cTBS induced mixed inhibitory and facilitatory/excitatory perturbations of M1, though with predominant inhibition. Although cTBS impacted on manual dexterity, its effects appear too limited and variable in order to use it as a reliable proof of cortical vicariation mechanism (cortical area replacing another one) underlying functional recovery following a cortical lesion in the motor control domain, in contrast to potent pharmacological block generated by muscimol infusion, whose application is though limited to an animal model such as non‐human primate.
Differentiation of ADHD and Depression Based on Cognitive Performance

Objective: The aim of this study was to assess whether self-report scales and neuropsychological tests used for adult patients with ADHD can help to distinguish between ADHD-specific and depressive symptoms. Method: In a cross-sectional design, differences in self-report questionnaires and neuropsychological tests among clinical subgroups and healthy controls (HC) were evaluated. Patients in clinical groups were diagnosed with major depressive disorder (MDD) or ADHD with or without depressive symptoms according to Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) guidelines. Results: The Hyperactivity subscales of the Conners’ Adult ADHD Rating Scale (CAARS) differed between MDD and ADHD, whereas self-concept and inattention scales even distinguished comorbidity subgroups within the ADHD population. A reduced alertness and higher variations in reaction times measured by performance tests indicated problems in sustained attention in ADHD patients compared with HC. Conclusion: The diagnostic process of ADHD, and thereby the distinction from other symptom-overlapping, comorbid mental disorders, might be improved by utilizing ADHD-specific self-report questionnaires and neuropsychological tests, which are short, cost-effective, and standardized screening methods.
Capacity utilization and the effects of energy price increases in Japan

It is well known that the standard real business cycle (RBC) model with energy cannot generate the large drops in value added following the energy price increases in the 1970s, although previous empirical studies have confirmed the important role of energy prices. In this paper, endogenous capacity utilization is incorporated into an otherwise standard RBC model as an amplification mechanism. The simulated results show that the endogenous capacity utilization successfully generates the large contraction in value added observed in the Japanese data. It is also shown that the introduction of capacity utilization produces more realistic dynamics of total factor productivity.
A 3D columnar phase of stacked short DNA organized by coherent membrane undulations.

We report on the discovery of a new organized lipid-nucleic acid phase upon intercalation of blunt duplexes of short DNA (sDNA) within cationic multilayer fluid membranes. End-to-end interactions between sDNA leads to columnar stacks. At high membrane charge density, with the inter-sDNA column spacing (dsDNA) comparable but larger than the diameter of sDNA, a 2D columnar phase (i.e. a 2D smectic) is found similar to the phase in cationic liposome-DNA complexes with long lambda-phage DNA. Remarkably, with increasing dsDNA as the membrane charge density is lowered, a transition is observed to a 3D columnar phase of stacked sDNA. This occurs even though direct DNA-DNA electrostatic interactions across layers are screened by diffusing cationic lipids near the phosphate groups of sDNA. Softening of the membrane bending rigidity (κ), which further promotes membrane undulations, significantly enhances the 3D columnar phase. These observations are consistent with a model by Schiessel and Aranda-Espinoza where local membrane undulations, due to electrostatically-induced membrane wrapping around sDNA columns, phase lock from layer-to-layer, thereby precipitating coherent "crystal-like" undulations coupled to sDNA columns with long-range position and orientation order. The finding that this new phase is stable at large dsDNA and enhanced with decreasing κ is further supportive of the model where the elastic cost of membrane deformation per unit area around sDNA columns (∝ κh2/dsDNA4, h2 = sum of square of amplitudes of the inner and outer monolayer undulations) is strongly reduced relative to the favorable electrostatic attractions of partially wrapped membrane around sDNA columns. The findings have broad implications in the design of membrane-mediated assembly of functional nanoparticles in 3D.
Decision Tree Methods for Predicting Surface Roughness in Fused Deposition Modeling Parts

3D printing using fused deposition modeling (FDM) includes a multitude of control parameters. It is difficult to predict a priori what surface finish will be achieved when certain values are set for these parameters. The objective of this work is to compare the models generated by decision tree algorithms (C4.5, random forest, and random tree) and to analyze which makes the best prediction of the surface roughness in polyethylene terephthalate glycol (PETG) parts printed in 3D using the FDM technique. The models have been created using a dataset of 27 instances with the following attributes: layer height, extrusion temperature, print speed, print acceleration, and flow rate. In addition, a dataset has been created to evaluate the models, consisting of 15 additional instances. The models generated by the random tree algorithm achieve the best results for predicting the surface roughness in FDM parts.
Dynamic chromatin targeting of BRD4 stimulates cardiac fibroblast activation

Small molecule inhibitors of the acetyl-histone binding protein BRD4 have been shown to block cardiac fibrosis in pre-clinical models of heart failure (HF). However, the mechanisms by which BRD4 promotes pathological myocardial fibrosis remain unclear. Here, we demonstrate that BRD4 functions as an effector of TGF-β signaling to stimulate conversion of quiescent cardiac fibroblasts into Periostin (Postn)-positive cells that express high levels of extracellular matrix. BRD4 undergoes stimulus-dependent, genome-wide redistribution in cardiac fibroblasts, becoming enriched on a subset of enhancers and super-enhancers, and leading to RNA polymerase II activation and expression of downstream target genes. Employing the SERTA domain-containing protein 4 (Sertad4) locus as a prototype, we demonstrate that dynamic chromatin targeting of BRD4 is controlled, in part, by p38 mitogen-activated protein kinase, and provide evidence of a novel function for Sertad4 in TGF-β-mediated cardiac fibroblast activation. These findings define BRD4 as a central regulator of the pro-fibrotic cell state of cardiac fibroblasts, and establish a signaling circuit for epigenetic reprogramming in HF.
Melatonin Improves the Fertilization Capacity of Sex-Sorted Bull Sperm by Inhibiting Apoptosis and Increasing Fertilization Capacitation via MT1

Little information is available regarding the effect of melatonin on the quality and fertilization capability of sex-sorted bull sperm, and even less about the associated mechanism. Sex-sorted sperm from three individual bulls were washed twice in wash medium and incubated in a fertilization medium for 1.5 h, and each was supplemented with melatonin (0, 10−3 M, 10−5 M, 10−7 M, and 10−9 M). The reactive oxygen species (ROS) and endogenous antioxidant activity (glutathione peroxidase (GPx); superoxide dismutase (SOD); catalase (CAT)), apoptosis (phosphatidylserine [PS] externalization; mitochondrial membrane potential (Δψm)), acrosomal integrity events (malondialdehyde (MDA) level; acrosomal integrity), capacitation (calcium ion [Ca2+]i level; cyclic adenosine monophosphate (cAMP); capacitation level), and fertilization ability of the sperm were assessed. Melatonin receptor 1 (MT1) and 2 (MT2) expression were examined to investigate the involvement of melatonin receptors on sex-sorted bull sperm capacitation. Our results show that treatment with 10−5 M melatonin significantly decreased the ROS level and increased the GPx, SOD, and CAT activities of sex-sorted bull sperm, which inhibited PS externalization and MDA levels, and improved Δψm, acrosomal integrity, and fertilization ability. Further experiments showed that melatonin regulates sperm capacitation via MT1. These findings contribute to improving the fertilization capacity of sex-sorted bull sperm and exploring the associated mechanism.
Distinct roles of ezrin, radixin and moesin in maintaining the plasma membrane localizations and functions of human blood–brain barrier transporters

The purpose of this study was to clarify the roles of ERM proteins (ezrin/radixin/moesin) in the regulation of membrane localization and transport activity of transporters at the human blood–brain barrier (BBB). Ezrin or moesin knockdown in a human in vitro BBB model cell line (hCMEC/D3) reduced both BCRP and GLUT1 protein expression levels on the plasma membrane. Radixin knockdown reduced not only BCRP and GLUT1, but also P-gp membrane expression. These results indicate that P-gp, BCRP and GLUT1 proteins are maintained on the plasma membrane via different ERM proteins. Furthermore, moesin knockdown caused the largest decrease of P-gp and BCRP efflux activity among the ERM proteins, whereas GLUT1 influx activity was similarly reduced by knockdown of each ERM protein. To investigate how moesin knockdown reduced P-gp efflux activity without loss of P-gp from the plasma membrane, we examined the role of PKCβI. PKCβI increased P-gp phosphorylation and reduced P-gp efflux activity. Radixin and moesin proteins were detected in isolated human brain capillaries, and their protein abundances were within a 3-fold range, compared with those in hCMEC/D3 cell line. These findings may mean that ezrin, radixin and moesin maintain the functions of different transporters in different ways at the human BBB.
A specific class of infectious agents isolated from bovine serum and dairy products and peritumoral colon cancer tissue

ABSTRACT The in silico analyses of 109 replication-competent genomic DNA sequences isolated from cow milk and its products (97 in the bovine meat and milk factors 2 group – BMMF2, and additional 4 in BMMF1) seems to place these in a specific class of infectious agents spanning between bacterial plasmid and circular ssDNA viruses. Satellite-type small plasmids with partial homology to larger genomes, were also isolated in both groups. A member of the BMMF1 group H1MBS.1 was recovered in a distinctly modified form from colon tissue by laser microdissection. Although the evolutionary origin is unknown, it draws the attention to the existence of a hitherto unrecognized, broad spectrum of potential pathogens. Indirect hints to the origin and structure of our isolates, as well as to their replicative behaviour, result from parallels drawn to the Hepatitis deltavirus genome structure and replication.
Ex situ Perfusion of Pancreas for Whole-Organ Transplantation: Is it Safe and Feasible? A Systematic Review

Introduction: Pancreas transplantation is currently one of the best treatments proposed in highly selected patients with unstable and brittle type 1 diabetes. The objective of pancreas transplantation is to restore normoglycemia and avoid the occurrence of complications associated with diabetes. Graft pancreatitis and thrombosis, arising from ischemia reperfusion injuries, are major causes of graft loss in the postoperative period. Ex situ perfusion, in hypothermic or normothermic settings, allowed to improve ischemic reperfusion injury in other organ transplantations (kidney, liver, or lung). The development of pancreatic graft perfusion techniques would limit these ischemic reperfusion injuries. Objective: Evaluation of the safety and feasibility of ex situ perfusion of pancreas for whole-organ transplantation. Methods: English literature about pancreas perfusion was analyzed using electronic database Medline via PubMed (1950-2018). Exclusion criteria were studies that did not specify the technical aspects of machine perfusion and studies focused only on pancreas perfusion for islet isolation. Results: Hypothermic machine perfusion for pancreas preservation has been evaluated in nine studies and normothermic machine perfusion in ten studies. We evaluated machine perfusion model, types of experimental model, anatomy, perfusion parameters, flushing and perfusion solution, length of perfusion, and comparison between static cold storage and perfusion. Conclusions: This review compared ex vivo machine perfusion of experimental pancreas for whole-organ transplantation. Pancreas perfusion is feasible and could be a helpful tool to evaluate pancreas prior to transplantation. Pancreas perfusion (in hypothermic or normothermic settings) could reduce ischemic reperfusion injuries, and maybe could avoid pancreas thrombosis and reduce morbidity of pancreas transplantation.
Effect of the Large and Small T-Antigens of Human Polyomaviruses on Signaling Pathways

Viruses are intracellular parasites that require a permissive host cell to express the viral genome and to produce new progeny virus particles. However, not all viral infections are productive and some viruses can induce carcinogenesis. Irrespective of the type of infection (productive or neoplastic), viruses hijack the host cell machinery to permit optimal viral replication or to transform the infected cell into a tumor cell. One mechanism viruses employ to reprogram the host cell is through interference with signaling pathways. Polyomaviruses are naked, double-stranded DNA viruses whose genome encodes the regulatory proteins large T-antigen and small t-antigen, and structural proteins that form the capsid. The large T-antigens and small t-antigens can interfere with several host signaling pathways. In this case, we review the interplay between the large T-antigens and small t-antigens with host signaling pathways and the biological consequences of these interactions.
Health-Risk Behaviors and Protective Factors Among Adolescents in Rural British Columbia.

PURPOSE This study explores the relationship between rural residency, selected protective factors (family and school connectedness along with prosocial peer attitudes), and health-compromising behaviors (alcohol and tobacco use and nonuse of seatbelt) among adolescents. METHODS A subsample of adolescents residing in remote areas was extracted from a province-wide, school-based survey in British Columbia (BC), Canada (weighted N = 2,999). We employed χ2 statistic to test rural-urban differences separately by gender. Logistic regression analysis was used to examine the relationship between protective factors and behaviors compromising health. FINDINGS In boys, rural residency was associated with multiple problem behaviors (binge drinking, smokeless tobacco use, and nonuse of seatbelt), whereas for girls it was linked to riding without a seatbelt. The final logistic regression models confirmed that rural environment was a significant risk factor for not wearing a seatbelt among both boys and girls, and smokeless tobacco among boys (adjusted odds ratio between 1.44 and 3.05). Rurality, on the other hand, did not predict binge drinking. Logistic regression analyses also revealed that both school connectedness and prosocial peer attitude protected boys against binge drinking and smokeless tobacco, but the results were not as robust for girls. CONCLUSIONS These findings could provide information for location-based intervention efforts promoting adolescent health, highlighting the protective role of the school atmosphere and prosocial peer relationships, especially among boys.