Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanisms for the increased fatigability of the lower limb in people with type 2 diabetes.

Fatiguing exercise is the basis of exercise training and a cornerstone of management of type 2 diabetes mellitus (T2D); however, little is known about the fatigability of limb muscles and the involved mechanisms in people with T2D. The purpose of this study was to compare fatigability of knee extensor muscles between people with T2D and controls without diabetes and determine the neural and muscular mechanisms for a dynamic fatiguing task. Seventeen people with T2D [ten men and seven women: 59.6 (9.0) yr] and twenty-one age-, body mass index-, and physical activity-matched controls [eleven men and ten women: 59.5 (9.6) yr] performed one hundred twenty high-velocity concentric contractions (one contraction/3 s) with a load equivalent to 20% maximal voluntary isometric contraction (MVIC) torque with the knee extensors. Transcranial magnetic stimulation (TMS) and electrical stimulation of the quadriceps were used to assess voluntary activation and contractile properties. People with T2D had larger reductions than controls in power during the fatiguing task [42.8 (24.2) vs. 26.4 (15.0)%; P < 0.001] and MVIC torque after the fatiguing task [37.6 (18.2) vs. 26.4 (12.1)%; P = 0.04]. People with T2D had greater reductions than controls in the electrically evoked twitch amplitude after the fatiguing task [44.0 (20.4) vs. 35.4 (12.1)%, respectively; P = 0.01]. However, the decrease in voluntary activation was similar between groups when assessed with electrical stimulation [12.1 (2.6) vs. 12.4 (4.4)% decrease; P = 0.84] and TMS ( P = 0.995). A greater decline in MVIC torque was associated with larger reductions of twitch amplitude ( r2 = 0.364, P = 0.002). Although neural mechanisms contributed to fatigability, contractile mechanisms were responsible for the greater knee extensor fatigability in men and women with T2D compared with healthy controls. NEW & NOTEWORTHY Transcranial magnetic stimulation and percutaneous muscle stimulation were used to determine the contributions of neural and contractile mechanisms of fatigability of the knee extensor muscles after a dynamic fatiguing task in men and women with type 2 diabetes (T2D) and healthy age-, body mass index-, and physical activity-matched controls. Although neural and contractile mechanisms contributed to greater fatigability of people with T2D, fatigability was primarily associated with impaired contractile mechanisms and glycemic control.
β-Catenin Knockdown Affects Mitochondrial Biogenesis and Lipid Metabolism in Breast Cancer Cells

β-catenin plays an important role as regulatory hub in several cellular processes including cell adhesion, metabolism, and epithelial mesenchymal transition. This is mainly achieved by its dual role as structural component of cadherin-based adherens junctions, and as a key nuclear effector of the Wnt pathway. For this dual role, different classes of proteins are differentially regulated via β-catenin dependent mechanisms. Here, we applied a liquid chromatography-mass spectrometry (LC-MS/MS) approach to identify proteins modulated after β-catenin knockdown in the breast cancer cell line MCF-7. We used a label free analysis to compare trypsin-digested proteins from CTR (shCTR) and β-catenin knockout cells (shβcat). This led to the identification of 98 differentially expressed proteins, 53 of them were up-regulated and 45 down-regulated. Loss of β-catenin induced morphological changes and a significant modulation of the expression levels of proteins associated with primary metabolic processes. In detail, proteins involved in carbohydrate metabolism and tricarboxylic acid cycle were found to be down-regulated, whereas proteins associated to lipid metabolism were found up-regulated in shβcat compared to shCTR. A loss of mitochondrial mass and membrane potential was also assessed by fluorescent probes in shβcat cells with respect to the controls. These data are consistent with the reduced expression of transcriptional factors regulating mitochondrial biogenesis detected in shβcat cells. β-catenin driven metabolic reprogramming resulted also in a significant modulation of lipogenic enzyme expression and activity. Compared to controls, β-catenin knockout cells showed increased incorporation of [1-14C]acetate and decreased utilization of [U-14C]glucose for fatty acid synthesis. Our data highlight a role of β-catenin in the regulation of metabolism and energy homeostasis in breast cancer cells.
AP-SWATH Reveals Direct Involvement of VCP/p97 in Integrated Stress Response Signaling Through Facilitating CReP/PPP1R15B Degradation *

The ubiquitin-directed AAA-ATPase VCP/p97 facilitates degradation of damaged or misfolded proteins in diverse cellular stress response pathways. Resolving the complexity of its interactions with partner and substrate proteins and understanding its links to stress signaling is therefore a major challenge. Here, we used affinity-purification SWATH mass spectrometry (AP-SWATH) to identify proteins that specifically interact with the substrate-trapping mutant, p97-E578Q. AP-SWATH identified differential interactions over a large detection range from abundant p97 cofactors to pathway-specific partners and individual ligases such as RNF185 and MUL1 that were trapped in p97-E578Q complexes. In addition, we identified various substrate proteins and candidates including the PP1 regulator CReP/PPP1R15B that dephosphorylates eIF2α and thus counteracts attenuation of translation by stress-kinases. We provide evidence that p97 with its Ufd1-Npl4 adapter ensures rapid constitutive turnover and balanced levels of CReP in unperturbed cells. Moreover, we show that p97-mediated degradation, together with a reduction in CReP synthesis, is essential for timely stress-induced reduction of CReP levels and, consequently, for robust eIF2α phosphorylation to enforce the stress response. Thus, our results demonstrate that p97 not only facilitates bulk degradation of misfolded proteins upon stress, but also directly modulates the integrated stress response at the level of signaling.
High Efficient Reduction of Graphene Oxide via Nascent Hydrogen at Room Temperature

To develop a green and efficient method to synthesize graphene in relative milder conditions is prerequisite for graphene applications. A chemical reducing method has been developed to high efficiently reduce graphene oxide (GO) using Fe2O3 and NH3BH3 as catalyst and reductants, respectively. During the process, environmental and strong reductive nascent hydrogen were generated surrounding the surface of GO sheets by catalyst hydrolysis reaction of NH3BH3 and were used for reduction of GO. The reduction process was studied by ultraviolet absorption spectroscopy, Raman spectroscopy, and Fourier transform infrared spectrum. The structure and morphology of the reduced GO were characterized with scanning electron microscopy and transmission electron microscopy. Compared to metal (Mg/Fe/Zn/Al) particles and acid system which also use nascent hydrogen to reduce GO, this method exhibited higher reduction efficiency (43.6%). Also the reduction was carried out at room temperature condition, which is environmentally friendly. As a supercapacitor electrode, the reversible capacity of reduced graphene oxide was 113.8 F g−1 at 1 A g−1 and the capacitance retention still remained at 90% after 200 cycles. This approach provides a new method to reduce GO with high reduction efficiency by green reductant.
The Role of Individual Disulfide Bonds of μ-Conotoxin GIIIA in the Inhibition of NaV1.4

μ-Conotoxin GIIIA, a peptide toxin isolated from Conus geographus, preferentially blocks the skeletal muscle sodium channel NaV1.4. GIIIA folds compactly to a pyramidal structure stabilized by three disulfide bonds. To assess the contributions of individual disulfide bonds of GIIIA to the blockade of NaV1.4, seven disulfide-deficient analogues were prepared and characterized, each with one, two, or three pairs of disulfide-bonded Cys residues replaced with Ala. The inhibitory potency of the analogues against NaV1.4 was assayed by whole cell patch-clamp on rNaV1.4, heterologously expressed in HEK293 cells. The corresponding IC50 values were 0.069 ± 0.005 μM for GIIIA, 2.1 ± 0.3 μM for GIIIA-1, 3.3 ± 0.2 μM for GIIIA-2, and 15.8 ± 0.8 μM for GIIIA-3 (-1, -2 and -3 represent the removal of disulfide bridges Cys3–Cys15, Cys4–Cys20 and Cys10–Cys21, respectively). Other analogues were not active enough for IC50 measurement. Our results indicate that all three disulfide bonds of GIIIA are required to produce effective inhibition of NaV1.4, and the removal of any one significantly lowers its sodium channel binding affinity. Cys10–Cys21 is the most important for the NaV1.4 potency.
BitTorrent Content Distribution in Optical Networks

In this paper, we extend our previous study on BitTorrent, the most popular peer-to-peer (P2P) protocol, to investigate different aspects related to its energy efficiency in IP over WDM (IP/WDM) networks, validating the power savings previously obtained by modeling and simulation through experimental results. Our contributions can be summarized as follows: First, we compare the energy consumption of our previously proposed energy efficient BitTorrent protocol to that of the original BitTorrent protocol and the client-server (C-S) schemes over bypass IP/WDM networks considering a range of network topologies with different number of nodes and average hop counts. Our results show that for a certain swarm size, the energy efficient BitTorrent protocol achieves higher power savings in networks with lower number of nodes as the opportunity to localize traffic increases. Second, we extend our previously developed energy efficient BitTorrent heuristic enhancing its performance by allowing peers to progressively traverse more hops in the network if the number of peers in the local node is not sufficient. Third, we extend our previously developed mixed integer linear programming model to optimize the location as well as the upload rates of operator controlled seeders (OCS) to mitigate the performance degradation caused by leechers leaving after finishing the downloading operation. Fourth, we compare the power consumption of video on demand (VoD) services delivered using content distribution networks (CDN), P2P, and a promising hybrid CDN-P2P architecture over bypass IP/WDM core networks. A MILP model is developed to carry out the comparison. We investigate two scenarios for the hybrid CDN-P2P architecture: the H-MinNPC model where the model minimizes the IP/WDM network power consumption and the H-MinTPC model where the model minimizes the total power consumption including the network and the CDN datacenters power consumption. Finally, we carry out an experimental evaluation of the original and energy efficient BitTorrent heuristics.
Improvement of Flux Pinning Properties of YBCO Superconducting Films with BaMeO3 (Me:Zr, Mn, Hf and Ir) Perovskite Nanoparticles by TFA- MOD Technique

Superconducting materials increase performances of machines by intensively using in MRI in medicine, thermal bolometer, energy stroge systems in transformer, magnetic separators, levitation, NMR, generators, engines, cables, superconducting wires and tapes, accelerators, electromagnets, and electronic transistors. In these applications, the high temperature superconductors (HTS) possess very high crtitical current density (J c) values at low temperature even in high magnetic fields. In these kinds of studies, many kinds of crystalline defects, such as fine precipitates of non-superconducting phases, dislocations, vacancies, grain boundaries, twin boundaries and so on, are considered to act as pinning centers. However, the J c values rapidly decrease with increasing temperature in magnetic field. The main reason of the J c depression is the lack of effective pinning in the structure. Depending on these reason, a novel technology has been developed by means of a nanostructure engineering to create artificial pinning centers in HTC materials. With this regard, increasing critical current density and improvement of flux pinning properties of YBa 2Cu 3O 6.57 (YBCO) superconducting films with BaMeO 3 (Me:Zr, Mn, Hf and Ir) perovskite nanodots, nanorods or nanoparticles, as pinning centers, on SrTiO 3 substrate were aimed.
Side Effect Perceptions and Their Impact on Treatment Decisions in Women

Background. Side effects prompt some patients to forego otherwise-beneficial therapies. This study explored which characteristics make side effects particularly aversive. Methods. We used a psychometric approach, originating from research on risk perception, to identify the factors (or components) underlying side effect perceptions. Women (N = 149) aged 40 to 74 years were recruited from a patient registry to complete an online experiment. Participants were presented with hypothetical scenarios in which an effective and necessary medication conferred a small risk of a single side effect (e.g., nausea, dizziness). They rated a broad range of side effects on several characteristics (e.g., embarrassing, treatable). In addition, we collected 4 measures of aversiveness for each side effect: choosing to take the medication, willingness to pay to avoid the side effect (WTP), negative affective attitude associated with the side effect, and how each side effect ranks among others in terms of undesirability. A principal components analysis (PCA) was used to identify the components underlying side effect perceptions. Then, for each aversiveness measure separately, regression analyses were used to determine which components predicted differences in aversiveness among the side effects. Results. The PCA revealed 4 components underlying side effect perceptions: affective challenge (e.g., frightening), social challenge (e.g., disfiguring), physical challenge (e.g., painful), and familiarity (e.g., common). Side effects perceived as affectively and physically challenging elicited the highest levels of aversiveness across all 4 measures. Conclusions. Understanding what side effect characteristics are most aversive may inform interventions to improve medical decisions and facilitate the translation of novel biomedical therapies into clinical practice.
Early PQQ supplementation has persistent long‐term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice

Nonalcoholic fatty liver disease (NAFLD) is widespread in adults and children. Early exposure to maternal obesity or Western‐style diet (WD) increases steatosis and oxidative stress in fetal liver and is associated with lifetime disease risk in the offspring. Pyrroloquinoline quinone (PQQ) is a natural antioxidant found in soil, enriched in human breast milk, and essential for development in mammals. We investigated whether a supplemental dose of PQQ, provided prenatally in a mouse model of diet‐induced obesity during pregnancy, could protect obese offspring from progression of NAFLD. PQQ treatment given pre‐ and postnatally in WD‐fed offspring had no effect on weight gain but increased metabolic flexibility while reducing body fat and liver lipids, compared with untreated obese offspring. Indices of NAFLD, including hepatic ceramide levels, oxidative stress, and expression of proinflammatory genes (Nos2, Nlrp3, Il6, and Ptgs2), were decreased in WD PQQ‐fed mice, concomitant with increased expression of fatty acid oxidation genes and decreased Pparg expression. Notably, these changes persisted even after PQQ withdrawal at weaning. Our results suggest that supplementation with PQQ, particularly during pregnancy and lactation, protects offspring from WD‐induced developmental programming of hepatic lipotoxicity and may help slow the advancing epidemic of NAFLD in the next generation. —Jonscher, K. R. , Stewart, M. S. , Alfonso‐Garcia, A. , DeFelice, B. C. , Wang, X. X. , Luo, Y. , Levi, M. , Heerwagen, M. J. R. , Janssen, R. C. , de la Houssaye, B. A. , Wiitala, E. , Florey, G. , Jonscher, R. L. , Potma, E. O. , Fiehn, O. Friedman, J. E. Early PQQ supplementation has persistent long‐term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice. FASEB J. 31, 1434–1448 (2017) www.fasebj. org
Efficient Content Verification in Named Data Networking

In Named Data Networking, contents are retrieved from network caches as well as the content server by their name. This aspect arises severe security concerns on content integrity. Especially, if poisoned contents lie in the network cache, called content store(CS), interests would be served by the poisoned content rather than they propagate toward the content server. Consequently, users whose interests pass through the contaminated CS cannot access the valid content. In order to resolve the problem, every content is verified before they are inserted into the CS. However, this built-in verification mechanism is not practically feasible due to its huge computational overhead. In this paper, we address problems of content integrity in NDN in details, including how to violate content integrity. We also propose a practical solution that efficiently detects poisoned contents from the CS with minimum overhead. Since the proposed scheme aligns to the basic NDN architecture, it is a practical and effective solution.
Does the Timing of Suicide Risk Assessments Influence Ratings of Risk Severity?

Clinicians are often tasked with identifying and managing patients who are at risk for suicide. Therefore, greater understanding of factors that impact the efficacy of suicide risk assessments (SRAs) are of critical importance. One potential factor that may affect assessments of risk severity is the timing of the evaluation during clinical interview. Given that some patients are reluctant to disclose suicide-related symptoms, it is possible that asking about suicide at the beginning of an interview elicits more false negatives. It is also possible that if risk assessments are conducted in a manner that is encouraging to the patient, timing does not significantly impact patient report. This study examined whether SRA timing within an initial intake interview affects risk severity ratings. Adult psychiatric outpatients (N = 169) were randomly assigned to receive an SRA during the beginning or middle of a 1-hr intake. We failed to find a significant difference in suicide risk ratings between those who were evaluated at the beginning compared to the middle of intake (14% vs. 15% rated at elevated risk). Findings were not moderated by age, gender, or attempt history. Our results provide preliminary evidence that the timing of SRA may not impact risk severity ratings.
A Conformationally Mobile Cysteine Residue (Cys-561) Modulates Na+ and H+ Activation of Human CNT3*

In humans, the SLC28 concentrative nucleoside transporter (CNT) protein family is represented by three Na+-coupled members; human CNT1 (hCNT1) and hCNT2 are pyrimidine and purine nucleoside-selective, respectively, whereas hCNT3 transports both purine and pyrimidine nucleosides and nucleoside drugs. Belonging to a phylogenetic CNT subfamily distinct from hCNT1/2, hCNT3 also mediates H+/nucleoside cotransport. Using heterologous expression in Xenopus oocytes, we have characterized a cysteineless version of hCNT3 (hCNT3C-). Processed normally to the cell surface, hCNT3C-exhibited hCNT3-like transport properties, but displayed a decrease in apparent affinity specific for Na+ and not H+. Site-directed mutagenesis experiments in wild-type and hCNT3C-backgrounds identified intramembranous Cys-561 as the residue responsible for this altered Na+-binding phenotype. Alanine at this position restored Na+ binding affinity, whereas substitution with larger neutral amino acids (threonine, valine, and isoleucine) abolished hCNT3 H+-dependent nucleoside transport activity. Independent of these findings, we have established that Cys-561 is located in a mobile region of the hCNT3 translocation pore adjacent to the nucleoside binding pocket and that access of p-chloromercuribenzene sulfonate to this residue reports a specific H+-induced conformational state of the protein ( Slugoski, M. D., Ng, A. M. L., Yao, S. Y. M., Smith, K. M., Lin, C. C., Zhang, J., Karpinski, E., Cass, C. E., Baldwin, S. A., and Young, J. D. (2008) J. Biol. Chem. 283, 8496-8507 ). The present investigation validates hCNT3C- as a template for substituted cysteine accessibility method studies of CNTs and reveals a pivotal functional role for Cys-561 in Na+- as well as H+-coupled modes of hCNT3 nucleoside transport.
Water vapor sorption and diffusion in wheat straw particles and their impact on the mass transfer properties of biocomposites

This work intends to decipher the role of hydrophilic fillers, wheat straw fibers (WSF), on the water vapor transfer properties (sorption and diffusion) of biocomposites based on poly(3-hydroxybutyrate-co-3-hydroxyvalerate), (PHBV) as matrix. Transfer in biocomposites, measured using dynamical vapor sorption measurement, is correlated to the transfer properties of each individual constituent and to the specific structural arrangements induced by the presence of particles inside the matrix. Increasing amounts of WSF particles in the PHBV matrix lead to an increase of the water vapor sorption (WVS) of the resulting composites. This is attributed to the high sorption of hydrophilic WSF as compared to that of the neat PHBV matrix. Water vapor diffusion in composites (around 0.13 × 10−11 m2 s−1 at 20°C whatever the filler content) is always lower than in the neat matrix (0.26 × 10−11 m2 s−1) although wheat straw displays high diffusivity values (1.84 × 10−11 m2 s−1). Such unexpected behavior is related to (1) changes of structure and properties of the WSF particle once embedded in the PHBV matrix, (2) changes in the polymer matrix structure and properties in contact with fibers, and also (3) to the representativeness of the filler diffusivity, which is difficult to appraise.