Miracle-dz/UniFAR-FTUs huggingface dataset:
Imaging mitochondrial dynamics in Xenopus CNS

Notable for producing ATP via oxidative phosphorylation, mitochondria also control calcium homeostasis, lipogenesis, the regulation of reactive oxygen species, and apoptosis. Even within relatively simple cells, mitochondria are heterogeneous with regard to their shape, abundance, movement and subcellular locations. They exist as interconnected, tubular networks, and as motile organelles that are transported along the cytoskeleton to distribute throughout cells. These spatial and morphological features reflect the variability in the organelle’s capacity to synthesize ATP and support the cells. Changes to mitochondria are believed to support cell function and fate, and mitochondrial dysfunction underlies disease in the nervous system. Here we describe an in vivo timelapse imaging approach to monitor and measure the movement and position of the mitochondria in cells of the developing brain albino Xenopus laevis tadpoles. The unparalleled benefit for using Xenopus for these experiments is that measurements of mitochondrial morphology and distribution in cells can be measured in vivo, where the surrounding neural circuitry and other inputs that influence these critical organelles remain intact. relative positions of the mitochondrial start and endpoints. The intensity (normalized to the maximum value of each timepoint) at the first, mid and last timepoints shows that the majority of the mitochondria along the radial process hold stabile positions over time. With the position of the mitochondria identified from the plot profile data in H, the average normalized intensity for each mitochondrion along the proximal-distal position of the cell can be calculated (I). The cumulative probability plot the position of the mitochondria suggests changes in the distribution along the process over time. With individual mitochondria identified from the Plot Profile results, the average
Randomized Controlled Trial of a National Commercial Health Plan-Level Mood Disorders Collaborative Care Intervention

OBJECTIVE: Mood disorders lead to significant functional impairment and are the costliest conditions for health plans. Few individuals with mood disorders have access to evidence-based Collaborative Chronic Care Models (CCMs) because most are seen in small-group practices (<20 providers) with limited capacity to deliver CCMs. In this single-bling randomized controlled trial, we determined whether a CCM delivered nationally in a U.S. health plan improved 12-month outcomes compared to usual care among enrollees with mood disorders. METHODS: Aetna insurance enrollees (N=238, mean age=41.1 years, 66.1% female) recently hospitalized for unipolar major depression or bipolar disorder provided informed consent, completed baseline assessments, and were randomized to usual care or CCM. The CCM included 10 sessions of the Life Goals self-management program and brief contacts to determine symptom status, delivered by phone by a Care Manager. Primary outcomes were changes in depression symptoms (Patient Health Questionnaire-PHQ-9) and mental health-related quality of life (Short Form-SF-12-item score) in 12 months. RESULTS: Participants receiving CCM had significantly lower adjusted mean PHQ-9 scores by −2.34 (95% CL=−4.18, −0.50, p=0.01) and higher adjusted mean SF-12 mental health scores by 3.21 CONCLUSIONS: Individuals receiving CCM compared to usual care had improved clinical outcomes, although substantial attrition may limit impact of health plan-level delivery of CCMs. Further research on the use of health plan-level interventions such as CCMs as alternatives to practice-based models is warranted.
New and Notable Tuning the Calcium Sensitivity of Cardiac Muscle

It is generally known that muscle contraction is produced by cyclic interaction of myosin heads (crossbridges) of thick filaments with actin thin filaments driven by ATP hydrolysis; a conformational change in an attached crossbridge produces a pulling force on the thin filaments toward the center of a sarcomere (1). The activation of this contractile process in both cardiac and skeletal muscles is regulated by the intracellular calcium ion concentration, [Ca2þ], and it operates via the thin (actin) filament; when [Ca2þ] rises, a muscle contracts, and when [Ca2þ] falls, a muscle relaxes. Troponin (Tn) is a constituent protein of thin filament and the protein to which Ca2þ binds to accomplish this regulation. Troponin has three subunits, TnC, TnI, and TnT. When calcium is bound to specific sites on TnC, tropomyosin (Tm, another protein in the thin filament) moves out of the way of the active actin sites in thin filament, so that crossbridges (molecular motors organized in muscle thick filaments) can attach to the thin filament and generate force and/or movement. In the absence of calcium, tropomyosin prevents this crossbridge operation, and therefore muscles remain relaxed. One of the long running mysteries of the thin filament regulation is why there are so many variants in the N-terminus
[Autofluorescence combined with spectral domain optical coherence tomography for diagnosis and follow-up of acute Vogt-Koyanagi-Harada disease].

OBJECTIVE To evaluate the value of fundus autofluorescence (FAF) imaging combined with spectral domain optical coherence tomography (SD-OCT) in diagnosis, prognostic assessment and follow-up observation of acute Vogt-KoyanagiHarada (VKH) disease. METHODS Clinical data were collected from 12 patients (23 eyes) with acute VKH disease treated in our hospital from May, 2018 to November, 2019, including detailed medical history, best corrected visual acuity (BCVA), and results of slit lamp biomicroscopy, fundus photography, SD-OCT, fundus fluorescein angiography (FFA) and FAF imaging.SDOCT and FAF imaging were repeated after a course of treatment and in follow-up examination, and the results were compared with those at the time of admission. RESULTS VKH disease involved both eyes in 11 patients (91.7%). Fundus photography showed optic disc edema in 16 eyes (69.6%), and multiple retinal neuroepithelial detachment was detected by SD-OCT in all the involved eyes (100%). IN all the eyes, FFA revealed small and dense fluorescein leakage in the early stage and fluorescein accumulation in advanced stages of VHK disease to form multiple dye pooling in the areas of serous detachment.Hyperauto fluorescence was a common finding in FAF imaging (100%), and the area involved was consistent with that of fluorescein accumulation shown by FAF imaging.Ten eyes (43.5%) showed patches of relative hypoautofluorescence in the hyperauto fl uorescence areas, and granular hyperauto fl uorescence was found in the lesions in 4 eyes (17.4%). During the remission period of VKH disease, FAF imaging showed normal finding in 8 eyes (34.8%) and reduced areas (by 55.2%) and intensity (by 46.5%) of hyperautofluorescence in 9 eyes (39.1%). In 6 eyes (26.1%), only a few hyperautofluorescent spots scattered in the macula were observed.SD-OCT demonstrated significantly reduced (by 69.5% on average) or even disappearance of subretinal fluid in the eyes.The fluorescence intensity in FAF imaging showed a significant positive correlation with the volume of subretinal fluid detected by SD-OCT (r=0.626, P < 0.05). CONCLUSIONS The combination of fluorescein angiography, FAF imaging and SD-OCT can significantly improve the diagnostic accuracy of VKH disease.FAF imaging combined with SD-OCT provides an effective and noninvasive modality for evaluation of remission and monitoring the changes in VKH disease.
Lack of Association Between HLA Antigen DR3 and α 1 -Antitrypsin Deficiency in Liver Transplant Recipients

The relationship between α 1 -antitrypsin deficiency ( α 1 -ATD) and the HLA antigen system was studied in 32 liver transplant recipients. Despite previous reports of an association of HLA antigen DR3 with homozygosity for α 1 -AT ZZ, no such association was seen in this population of α 1 ATD homozygous ZZ patients with advanced hepatic disease. Thus, the reported association of HLA class II antigens and homozygosity for the Z allele for α 1 -AT may be an artifact of either a small study population or geographic inbreeding and a coincidental association of certain HLA antigens with the presence of homozygosity for the Z allele of α 1 -AT.
Effects of Mild Hypothermia Treatment on Rat Hippocampal b -Amyloid Expression Following Traumatic Brain Injury

Previous studies have reported that mild induced hypothermia (MIH) treatment has positive effects on traumatic brain injury (TBI) outcomes, which have recently been linked to b -amyloid (A b )-induced secondary brain injury (SBI) extent in hippocampal tissues. We therefore investigate the relationship between MIH treatment and expression of A b and related proteins following TBI. Adult Sprague-Dawley rats were randomly divided into three equal groups (S: sham-operated, N: normothermia, and H: mild hypothermia). After TBI induced by ﬂuid percussion, group N remained at normal temperature, and group H underwent MIH (32 (cid:2) C) for 6 hours. Behavioral scale scores were then assessed. All rats were sacriﬁced 24 hours and hippocampal tissues were harvested, stained with hematoxylin and eosin. mRNA and protein expressions of A b , b -amyloid protein precursor (APP), and b -secretase (BACE) were analyzed. Our results revealed signiﬁcantly improved behavioral scale scores and the surviving neuron numbers were observed in group H compared to group N ( p < 0.05). Additionally, group N increased APP, A b , and BACE levels compared to group S (all p < 0.05). Reduced expression of APP-, A b -, and BACE were apparent in group H compared to group N (all p < 0.05). However, no statistically signiﬁcant difference was observed between groups H and S in behavioral scale scores and the expression of APP-, A b -, and BACE ( p > 0.05). In conclusion, MIH treatment signiﬁcantly improves the survival of neuron and reduced A b , BACE, and APP upregulation after TBI, which may provide a better understanding of the mechanisms by which hypothermia reduces SBI in TBI patients.
AJA150029 14..24

Purpose: This study investigated (a) the effect of amplification on cortical auditory evoked potentials (CAEPs) at different signal levels when signal-to-noise ratios (SNRs) were equated between unaided and aided conditions, and (b) the effect of absolute signal level on aided CAEPs when SNR was held constant. Method: CAEPs were recorded from 13 young adults with normal hearing. A 1000-Hz pure tone was presented in unaided and aided conditions with a linear analog hearing aid. Direct audio input was used, allowing recorded hearing aid noise floor to be added to unaided conditions to equate
Entrainment revisited: a commentary on Meyer, Sun & Martin (2020)

Almost a century ago, Bishop proposed that brain oscillations reflect rhythmic fluctuations of neuronal populations between high and low excitability states (Bishop, 1932). While the implications of this fundamental proposition are still actively debated, a large body of research supports the idea that oscillations are instrumental rather than incidental to brain operations (for review, see, e.g., Buzsáki, 2006; Schroeder and Lakatos, 2009; Wang, 2010).
Feasibility study of Fiber Reinforced Polymer Railway Bridges

The Netherlands has one of the busiest rail network in the Europe (Oliver Wyman, 2016) that is growing rapidly due to the limited rail network and improved inter-connectivity with road and marine transportation mode. Because of intensifying rail traffic and ageing rail bridge infrastructure (Archives: Arcadis), the rail bridge infrastructure comprising of steel bridges is deteriorating. The simple old and small span steel railway bridges have approached their service life and are outdated according to OVS guidelines in terms of safety, repair and inspection. In addition, the issue of structural degradation because of corrosion, noise emission in the neighborhood and fatigue resistance adds to the severity of this scenario.
Serum Levels of Neuron-Specific UCHL1 Predict Brain Injury in a Canine Model of Hypothermic Circulatory Arrest

Background— Ubiquitin carboxyl-terminal esterase-L1 (UCHL1) is a protein highly selectively expressed in neurons and has been linked to neurodegenerative disease in humans. We hypothesize that UCHL1 would be an effective serum biomarker for brain injury as tested in canine models of hypothermic circulatory arrest (HCA) and cardiopulmonary bypass (CPB). Methods— Canines were exposed to CPB (n=14), 1 hour(h) HCA (n=11), or 2h-HCA (n=20). Cerebrospinal fluid (CSF) and serum were collected at baseline, 8h, and 24h post-treatment. UCHL1 levels were measured using a sandwich enzyme-linked immunosorbent assay (ELISA). Neurological function and histopathology were scored at 24h, UCHL1 immunoreactivity protein similar for all UCHL1 levels were elevated at 8h post-treatment for 2h-HCA subjects compared to baseline values (p<0.01), also compared to CPB canines at 8h (p<0.01). A serum UCHL1 3.9ng/(mg total protein) 8h the best discriminatory functional CSF, UCHL1 all 8h post-treatment compared to baseline (p<0.01). UCHL1 levels in CSF remained elevated at 24h only in 2h-HCA subjects (p<0.01). and histopathology were closely correlated coefficient: 0.66; p<0.01), significantly worse in 2h-HCA HCA animals compared with CPB animals. These results support the potential for use in cardiac surgery patients, and form the basis for clinical correlation in humans.
Release from myosin V via regulated recruitment of an E3 Ub ligase controls organelle localization

Summary Molecular motors transport organelles to specific subcellular locations. Upon arrival at their correct locations, motors release organelles via unknown mechanisms. The yeast myosin-V, Myo2, binds the vacuole specific adaptor, Vac17, to transport the vacuole from the mother cell to the bud. Here, we show that vacuole detachment from Myo2 occurs in multiple regulated steps along the entire pathway of vacuole transport. Detachment initiates in the mother cell with the phosphorylation of Vac17 which recruits the E3 ligase, Dma1, to the vacuole. However, Dma1 recruitment also requires the assembly of the vacuole transport complex and is first observed after the vacuole enters the bud. Dma1 remains on the vacuole until the bud and mother vacuoles separate. Subsequently, Dma1 targets Vac17 for proteasomal degradation. Notably, we find that the termination of peroxisome transport also requires Dma1. We predict that this is a general mechanism which detaches myosin-V from select cargoes. results demonstrate that Thr240 phosphorylation creates a binding site on Vac17 critical for the recruitment of Dma1 to the vacuole. Intriguingly, while phosphorylation of Vac17-Thr240 occurs in the mother cell and does not require the attachment of Myo2 to vacuole, Dma1 is first observed on the vacuole in the bud and its recruitment to the vacuole Myo2. This suggests that either Dma1 recognizes the intact Myo2/Vac17/Vac8 vacuole transport or that Dma1 is recruited to the vacuole in the bud. Furthermore, these results suggest that Thr240 phosphorylation is required but not sufficient for Dma1 our results suggest that the regulated Dma1 critical
THE EFFECT OF IMATINIB ON CMV REACTIVATION IN HEMATOPOIETIC CELL TRANSPLANTATION

In-vitro studies have shown possible antiviral effects of tyrosine kinase (TK) inhibitors. In a retrospective study, we show that use of the TK inhibitor Imatinib does not appear to reduce cytomegalovirus reactivation during the first 100 days after transplant in a cohort of hematopoietic cell transplant recipients. in platelet and with mutation in c-kit A recent in-vitro study demonstrated that Imatinib inhibited the TK PDGFR- α , a critical receptor required for CMV infection, suggesting that it could be a novel therapy for either treatment or prevention of primary infection Other studies suggested that Imatinib may have antiviral activities but increased of varicella-zoster virus (VZV) in patients treated with this also Despite these observations, there are no clinical data evaluating the anti-CMV effects of Imatinib. We analyzed CMV outcomes in a cohort of hematopoietic cell transplant (HCT) recipients treated with or without Imatinib to assess the drug’s potential effects on CMV.
Na (cid:49) pump low and high ouabain affinity (cid:97) subunit isoforms are differently distributed in cells

Three isoforms ( (cid:97) 1, (cid:97) 2, and (cid:97) 3) of the catalytic ( (cid:97) ) subunit of the plasma membrane (PM) Na (cid:49) pump have been identified in the tissues of birds and mammals. These isoforms differ in their affinities for ions and for the Na (cid:49) pump inhibitor, ouabain. In the rat, (cid:97) 1 has an unusually low affinity for ouabain. The PM of most rat cells contains both low ( (cid:97) 1) and high ( (cid:97) 2 or (cid:97) 3) ouabain affinity isoforms, but precise localization of specific isoforms, and their functional significance, are unknown. We employed high resolution immunocytochemical techniques to localize (cid:97) subunit isoforms in primary cultured rat astrocytes, neurons, and arterial myocytes. Isoform (cid:97) 1 was ubiquitously distributed over the surfaces of these cells. In contrast, high ouabain affinity isoforms ( (cid:97) 2 in astrocytes, (cid:97) 3 in neurons and myocytes) were confined to a reticular distribution within the PM that paralleled underlying endoplasmic or sarcoplasmic reticulum. This distribution is identical to that of the PM Na (cid:121) Ca exchanger. This raises the possibility that (cid:97) 1 may regulate bulk cytosolic Na (cid:49) , whereas (cid:97) 2 and (cid:97) 3 may
Liver in the analysis of body composition by dual-energy X-ray absorptiometry

Objective: To investigate the predictive value for hepatic steatosis of a new software for the quantifi-cation of visceral fat by dual-energy X-ray absorptiometry (DXA) and to design new regions of interest (ROIs). Methods: Adult volunteers were prospectively screened for hepatic steatosis by ultrasonography to obtain a well-balanced population according to the presence/absence of the disease. 90 adult patients without steatosis and 90 with steatosis (mild, 53.3%; moderate, 37.7%; and severe, 10.0%) were recruited. On the same day, all subjects were submitted to blood testing and
Molecular suction pads: Self-assembled monolayers of subphthalocyaninatoboron complexes [BCl{Subpc’(SR) 6 }] on gold

Subphthalocyaninatoboron complexes with six long-chain alkylthio substituents in their periphery are applicable for the formation of self-assembled monolayers (SAMs) on gold. Such films were prepared from solution with the axially chlorido substituted derivatives and characterised by near-edge X-ray absorption fine structure (NEXAFS) spectroscopy, X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). The results are in accord with the formation of SAMs assembled by the chemisorption of both covalently bound thiolate-type as well as coordinatively bound thioether units. The adsorbate molecules adopt an essentially ‘flat’ adsorption geometry on the substrate, resembling a suction pad on a surface. Graphical Abstract
β -Amyloid Impairs the Regulation of NMDA Receptors by Glycogen Synthase Kinase 3

Accumulating evidence suggests that glycogen synthase kinase 3 (GSK-3) is a multifunctional kinase implicated in Alzheimer’s disease (AD). However, the synaptic actions of GSK-3 in AD conditions are largely unknown. In this study, we examined the impact of GSK-3 on NMDA receptor (NMDAR) channels, the major mediator of synaptic plasticity. Application of GSK-3 inhibitors or knockdown of GSK-3 caused a significant reduction of NMDAR-mediated ionic and synaptic current in cortical neurons, while this effect of GSK-3 was impaired in cortical neurons treated with β -amyloid (A β ) or from transgenic mice over-expressing mutant amyloid precursor protein (APP). GSK-3 activity was elevated by A β , and GSK-3 inhibitors failed to decrease the surface expression of NR1 and NR1/PSD-95 interaction in APP mice, which was associated with the diminished GSK-3 regulation of Rab5 activity that mediates NMDAR internalization. Consequently, GSK-3 inhibitor lost the capability of protecting neurons against NMDA-induced excitotoxicity in A β -treated neurons. These results have provided a novel mechanism underlying the involvement of GSK-3 in AD. was significantly higher in cortical slices from APP mice (166.8 ± 16.3% of WT, n = 3, p < 0.01, t-test). These data suggest that GSK-3 kinase activity is increased in APP mice.
Detection of Pathogenic Bacteria From Septic Patients Using 16S Ribosomal RNA Gene–Targeted Metagenomic Sequencing

gram-positive cocci, and 1 both gram-negative bacilli and gram-positive cocci. 16S rRNA gene NGS findings were concordant in 11. For the remaining 8, 16S rRNA gene NGS results yielded discordant detections (n = 5) or were negative (n = 3). Interestingly, Clostridium species were additionally detected by 16S rRNA gene NGS in 3 of the 6 subjects with gastrointestinal sources of gram-negative bacteremia and none of the 3 subjects with urinary sources of gram-negative bacteremia. In the 41 remaining subjects, 16S rRNA gene NGS detected at least 1 potentially pathogenic organism in 17. In 15, the detected microorganism clinically correlated with the patient’s syndrome. In 17 subjects with a clinically defined infectious syndrome, neither test was positive; in the remaining 7 subjects, a noninfectious cause of clinical presentation was identified. Conclusions. 16S rRNA gene NGS may be useful for detecting bacteria in plasma of septic patients. In some cases of gram-negative sepsis, it may be possible to pinpoint a gastrointestinal or urinary source of sepsis based on the profile of bacteria detected in plasma.
Constitutive activity of the d -opioid receptor expressed in C6 glioma cells: identiﬁcation of non-peptide d -inverse agonists

1 G-protein coupled receptors can exhibit constitutive activity resulting in the formation of active ternary complexes in the absence of an agonist. In this study we have investigated constitutive activity in C6 glioma cells expressing either the cloned d -(OP 1 ) receptor (C6 d ), or the cloned m -(OP 3 ) opioid receptor (C6 m ). 2 Constitutive activity was measured in the absence of Na + ions to provide an increased signal. The degree of constitutive activity was deﬁned as the level of [ 35 S]-GTP g S binding that could be inhibited by pre-treatment with pertussis toxin (PTX). In C6 d cells the level of basal [ 35 S]-GTP g S binding was reduced by 51.9 + 6.1 fmols mg 7 1 protein, whereas in C6 m and C6 wild-type cells treatment with PTX reduced basal [ 35 S]-GTP g S binding by only 10.0 + 3.5 and 8.6 + 3.1 fmols mg 7 1 protein respectively. 3 The d -antagonists N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI 174,864), 7-benzylidenenaltrexone (BNTX) and naltriben (NTB), in addition to clocinnamox (C-CAM), acted as d -opioid receptor inverse agonists. Naloxone, buprenorphine, and naltrindole were neutral antagonists. Furthermore, naltrindole blocked the reduction in [ 35 S]-GTP g S binding caused by the inverse agonists. The inverse agonists did not inhibit basal [ 35 S]-GTP g S binding in C6 m or C6 wild-type cell membranes. 4 Competition binding assays in C6 d cell membranes revealed a leftward shift in the displacement curve of [ 3 H]-naltrindole by ICI 174,864 and C-CAM in the presence of NaCl and the GTP analogue, GppNHp. There was no change in the displacement curve for BNTX or NTB under these conditions. 5 These data conﬁrm the presence of constitutive activity associated with the d -opioid receptor and identify three novel, non-peptide, d -opioid inverse agonists.