Miracle-dz/UniFAR-FTUs huggingface dataset:
Dystrophin-glycoprotein complex is highly enriched in isolated skeletal muscle sarcolemma

mAbs specific for protein components of the surface membrane of rabbit skeletal muscle have been used as markers in the isolation and characterization of skeletal muscle sarcolemma membranes. Highly purified sarcolemma membranes from rabbit skeletal muscle were isolated from a crude surface membrane preparation by wheat germ agglutination. Immunoblot analysis of subcellular fractions from skeletal muscle revealed that dystrophin and its associated glycoproteins of 156 and 50 kD are greatly enriched in purified sarcolemma vesicles. The purified sarcolemma was also enriched in novel sarcolemma markers (SL45, SL/TS230) and Na+/K(+)-ATPase, whereas t-tubule markers (alpha 1 and alpha 2 subunits of dihydropyridine receptor, TS28) and sarcoplasmic reticulum markers (Ca2(+)-ATPase, ryanodine receptor) were greatly diminished in this preparation. Analysis of isolated sarcolemma by SDS- PAGE and densitometric scanning demonstrated that dystrophin made up 2% of the total protein in the rabbit sarcolemma preparation. Therefore, our results demonstrate that although dystrophin is a minor muscle protein it is a major constituent of the sarcolemma membrane in skeletal muscle. Thus the absence of dystrophin in Duchenne muscular dystrophy may result in a major disruption of the cytoskeletal network underlying the sarcolemma in dystrophic muscle.
Frequent Mutations in TP 53 and CDKN 2 A Found by Next-Generation Sequencing of Head and Neck Cancer Cell Lines

Objective: To conduct high-throughput mutational analysis in 6 commonly used head and neck cancer cell lines. Comprehensive mutation analysis of primary head and neck squamous cell carcinoma (HNSCC) tumors has recently been reported, and mutations in the NOTCH receptors, TP53 and CDKN2A, were key findings. Established cell lines are valuable tools to study cancer in vitro. Similar high-throughput mutational analysis of head and neck cancer cell lines is necessary to confirm their mutational profile.
The effects of delayed plumage maturation on aggression and survival in male red-backed fairy-wrens

The occurrence of multiple phenotypes within a sex of a single species has long puzzled behavioral ecologists. Male red-backed fairy-wrens Malurus melanocephalus exhibit 3 behaviorally distinct types in their first breeding season: breed in bright nuptial plumage, breed in dull plumage, or remain as an unpaired auxiliary (helper) with dull plumage. The retention of dull plumage by auxiliaries and dull breeders is an example of delayed plumage maturation (DPM), a widespread phenomenon in birds whose costs and benefits are not well understood. At a mechanistic level, DPM might allow dull males either to deceptively mimic females (female mimicry hypothesis) or to honestly signal their subordinate status (status-signaling hypothesis). DPM might function via either mechanism to provide ultimate benefits relative to developing nuptial plumage by increasing reproductive success, survival, or both. In this study, we tested the hypothesis that DPM is related to increased male survival in the red-backed fairy-wren via either female mimicry or status signaling. Aviary-based experiments revealed that dull males were perceived as male, which is consistent with the status-signaling hypothesis but contradicts the female mimicry hypothesis. Further aviary and field-based experiments also revealed that dull males were socially subordinate to bright males and received less aggression than bright males, further evidence for status signaling. However, male survival was not related to plumage coloration or breeding status. These findings indicate that male plumage coloration signals social status but that dull plumage does not afford a net survival advantage, perhaps because plumage color is a conditional strategy. Copyright 2008, Oxford University Press.
Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α‐glucosidase inhibitor or a Nrf2‐inducer

The National Institute on Aging Interventions Testing Program (ITP) evaluates agents hypothesized to increase healthy lifespan in genetically heterogeneous mice. Each compound is tested in parallel at three sites, and all results are published. We report the effects of lifelong treatment of mice with four agents not previously tested: Protandim, fish oil, ursodeoxycholic acid (UDCA) and metformin – the latter with and without rapamycin, and two drugs previously examined: 17‐α‐estradiol and nordihydroguaiaretic acid (NDGA), at doses greater and less than used previously. 17‐α‐estradiol at a threefold higher dose robustly extended both median and maximal lifespan, but still only in males. The male‐specific extension of median lifespan by NDGA was replicated at the original dose, and using doses threefold lower and higher. The effects of NDGA were dose dependent and male specific but without an effect on maximal lifespan. Protandim, a mixture of botanical extracts that activate Nrf2, extended median lifespan in males only. Metformin alone, at a dose of 0.1% in the diet, did not significantly extend lifespan. Metformin (0.1%) combined with rapamycin (14 ppm) robustly extended lifespan, suggestive of an added benefit, based on historical comparison with earlier studies of rapamycin given alone. The α‐glucosidase inhibitor, acarbose, at a concentration previously tested (1000 ppm), significantly increased median longevity in males and 90th percentile lifespan in both sexes, even when treatment was started at 16 months. Neither fish oil nor UDCA extended lifespan. These results underscore the reproducibility of ITP longevity studies and illustrate the importance of identifying optimal doses in lifespan studies.
3,5-Diiodo-L-Thyronine Affects Structural and Metabolic Features of Skeletal Muscle Mitochondria in High-Fat-Diet Fed Rats Producing a Co-adaptation to the Glycolytic Fiber Phenotype

Hyperlipidemic state-associated perturbations in the network of factors controlling mitochondrial functions, i. e. , morphogenesis machinery and metabolic sensor proteins, produce metabolic inflexibility, insulin resistance and reduced oxidative capacity in skeletal muscle. Moreover, intramyocellular lipid (IMCL) accumulation leads to tissue damage and inflammation. The administration of the naturally occurring metabolite 3,5-diiodo-L-thyronine (T2) with thyromimetic actions to high fat diet (HFD)-fed rats exerts a systemic hypolipidemic effect, which produces a lack of IMCL accumulation, a shift toward glycolytic fibers and amelioration of insulin sensitivity in gastrocnemius muscle. In this study, an integrated approach combining large-scale expression profile and functional analyses was used to characterize the response of skeletal muscle mitochondria to T2 during a HFD regimen. Long-term T2 administration to HDF rats induced a glycolytic phenotype of gastrocnemius muscle as well as an adaptation of mitochondria to the fiber type, with a decreased representation of enzymes involved in mitochondrial oxidative metabolism. At the same time, T2 stimulated the activity of individual respiratory complex I, IV, and V. Moreover, T2 prevented the HFD-associated increase in the expression of peroxisome proliferative activated receptor γ coactivator-1α and dynamin-1-like protein as well as mitochondrial morphological aberrations, favoring the appearance of tubular and tethered organelles in the intermyofibrillar regions. Remarkably, T2 reverted the HDF-associated expression pattern of proinflammatory factors, such as p65 subunit of NF-kB, and increased the fiber-specific immunoreactivity of adipose differentiation–related protein in lipid droplets. All together, these results further support a role of T2 in counteracting in vivo some of the HFD-induced impairment in structural/metabolic features of skeletal muscle by impacting the mitochondrial phenotype.
Potentiation of the anticancer effects of everolimus using a dual mTORC1/2 inhibitor in hepatocellular carcinoma cells

There is lots of evidence to support the critical involvement of mTOR signaling in the carcinogenesis of hepatocellular carcinoma (HCC). However, it has not been determined how the roles of individual mTORC1 and mTORC2 inhibitors played in the HCC therapeutics. We thus compared the effects of everolimus, Ku0063794, and a combination of the two therapies on HCC cells, using various in vitro studies (HepG2, Hep3B, and Huh7 cells), ex vivo culturing of HCC tissues obtained from patients, and the in vivo mouse xenograft model of HCC cells. Our in vitro, ex vivo, and in vivo experiments consistently demonstrated that everolimus and Ku0063794 combination therapy was superior to individual monotherapies, as manifested by higher reduction of proliferation, migration, and invasion of HCC cells, and the higher inhibition of EMT process as well. Although individual monotherapies could not inhibit SIRT1 (positive regulator of EMT) expression, the combination therapy significantly inhibited SIRT1 expression. However, overexpression of SIRT1 mitigated the EMT-inhibiting effect of the combination therapy, suggesting that the combination therapy inhibits the EMT by way of suppressing SIRT1 expression. Therefore, when considering everolimus as an anti-HCC agent, the improved anticancer effects provided by combining it with an inhibitor of both mTORC1 and mTORC2 should be recognized.
Predictors of Intent to Leave the Job Among Home Health Workers: Analysis of the National Home Health Aide Survey

Purpose To identify agency policies and workplace characteristics that are associated with intent to leave the job among home health workers employed by certified agencies. Design and Methods Data are from the 2007 National Home and Hospice Care Survey/National Home Health Aide Survey, a nationally representative, linked data set of home health and hospice agencies and their workers. Logistic regression with survey weights was conducted to identify agency and workplace factors associated with intent to leave the job, controlling for worker, agency, and labor market characteristics. Results Job satisfaction, consistent patient assignment, and provision of health insurance were associated with lower intent to leave the job. By contrast, being assigned insufficient work hours and on-the-job injuries were associated with greater intent to leave the job after controlling for fixed worker, agency, and labor market characteristics. African American workers and workers with a higher household income also expressed greater intent to leave the job. Implications This is the first analysis to use a weighted, nationally representative sample of home health workers linked with agency-level data. The findings suggest that intention to leave the job may be reduced through policies that prevent injuries, improve consistency of client assignment, improve experiences among African American workers, and offer sufficient hours to workers who want them.
Atmospheric Ice‐Nucleating Particles in the Dusty Tropical Atlantic

Desert dust is one of the most important atmospheric ice‐nucleating aerosol species around the globe. However, there have been very few measurements of ice‐nucleating particle (INP) concentrations in dusty air close to desert sources. In this study we report the concentration of INPs in dust laden air over the tropical Atlantic within a few days' transport of one of the world's most important atmospheric sources of desert dust, the Sahara. These measurements were performed as part of the Ice in Clouds Experiment‐Dust campaign based in Cape Verde, during August 2015. INP concentrations active in the immersion mode, determined using a droplet‐on‐filter technique, ranged from around 102 m−3 at −12°C to around 105 m−3 at −23°C. There is about 2 orders of magnitude variability in INP concentration for a particular temperature, which is determined largely by the variability in atmospheric dust loading. These measurements were made at altitudes from 30 to 3,500 m in air containing a range of dust loadings. The ice active site density (ns) for desert dust dominated aerosol derived from our measurements agrees with several laboratory‐based parameterizations for ice nucleation by desert dust within 1 to 2 orders of magnitude. The small variability in ns values determined from our measurements (within about 1 order of magnitude) is striking given that the back trajectory analysis suggests that the sources of dust were geographically diverse. This is consistent with previous work, which indicates that desert dust's ice‐nucleating activity is only weakly dependent on source.
Iterative Design and Evaluation of Regulatory Network Visualisation at Scale

Over the last decade, the development of a range of Next Generation Sequencing (NGS) technologies has led to an enormous increase in the size of the data sets available in molecular biology. The scale of these data presents new challenges for researchers, and visualisation is widely regarded as an essential tool for exploration and detailed analysis of candidate relationships. Inevitably, there are cognitive and technical limits on the information which may usefully be displayed on a particular device, and there may be some tension between the analytical utility of a representation and its coverage of the relationships available within the data. Careful attention must be given to the overall design of the visualisation, and to the channels selected, and these tasks are further complicated if the intent is to support interactive exploration by a number of collocated researchers or inclusion within a collaborative workflow. This paper is concerned with the design of a visualisation for regulatory interactions in bacteria, the complex relationships that exist between a set of proteins and the much larger set of genes whose action they control. Modelling these interactions yields equally complex network diagrams, and even classical hairball representations when visualised. In this work we explore the iterative refinement of an alternative visualisation for data of this kind, moving away from the traditional hairball to a 'field' of smaller structures, the intent being to support effective comparison across many dozens of strains and species rather than the exhaustive documentation of a full set of interactions for the one organism. While the study did not directly compare insights obtained using TRNDiff with those obtained using other tools, formal evaluations have allowed us to settle on an effective set of representations and visual channels, and interactive features to support analysis. Our approach has produced a far more effective visualisation of these important data sets, and offers useful lessons for tool developers and insights into the utility of touch devices and larger displays for visual analytics and generation of insight at scale.
Cloning and expression profiling of odorant‐binding proteins in the tarnished plant bug, Lygus lineolaris

In insects, the perception and discrimination of odorants requires the involvement of odorant‐binding proteins (OBPs). To gain a better molecular understanding of olfaction in the agronomic pest Lygus lineolaris (the tarnished plant bug), we used a transcriptomics‐based approach to identify potential OBPs. In total, 33 putative OBP transcripts, including the previously reported Lygus antennal protein (LAP), were identified based on the characteristic OBP Cys signature and/or sequence similarity with annotated orthologous sequences. The L. lineolaris OBP (LylinOBP) repertoire consists of 20 ‘classic’ OBPs, defined by the spacing of six conserved Cys residues, and 12 ‘Plus‐C’ OBPs, defined by the spacing of eight conserved Cys and one conserved Pro residue. Alternative splicing of OBP genes appears to contribute significantly to the multiplicity of LylinOBP sequences. Microarray‐based analysis of chemosensory tissues (antennae, legs and proboscis) revealed enrichment of 21 LylinOBP transcripts in antennae, 12 in legs, and 15 in proboscis, suggesting potential roles in olfaction and gustation respectively. PCR‐based determination of transcript abundance for a subset of the LylinOBP genes across multiple adult tissues yielded results consistent with the hybridization data.
Use of cerebral oxygen saturation and hemoglobin concentration to predict acute kidney injury after cardiac surgery

Objective Acute kidney injury (AKI) is a common complication after cardiac surgery and is associated with significant morbidity and mortality. Near infrared spectroscopy (NIRS) is a noninvasive technique for real-time measurement of cerebral tissue oxygenation. The purpose of the present study was to evaluate the correlation of AKI with hemoglobin and regional cerebral oxygen saturation (rScO2) measured intraoperatively and postoperatively in patients undergoing cardiac surgery. Methods We retrospectively analyzed the prospectively collected data of 45 adult patients with normal renal function who underwent isolated coronary artery bypass grafting (CABG) from January 2014 to May 2014. Kidney injury was assessed according to the Acute Kidney Injury Network criteria. rScO2 and hemoglobin were measured every hour intraoperatively and for the first 24 hours postoperatively. Results The hemoglobin concentration and rScO2 were significantly lower in patients with than without AKI, and no linear trends were observed. No exact cut-off values were obtained. Conclusion This retrospective study shows that a lower rScO2 and hemoglobin concentration are correlated with AKI after CABG in patients with no peripheral vascular disease or recent myocardial infarction. We suggest that cerebral oximetry alone may predict postoperative AKI well.
PHASE TRANSFORMATIONS IN SILICON UNDER CONTACT LOADING

This review provides an analysis of the state of the art in the emerging research area of high-pressure surface science of silicon. Phase transformations and amorphization that occur in silicon under contact loading, such as indentation with hard indenters, scratching or machining, will be described. Contact loading is one of the most common mechanical impacts that materials can experience during processing or use. Examples are dicing, slicing, grinding, polishing and other machining operations. This kind of loading may be accommodated by such competing processes as dislocation-induced plasticity, microfracture, mechanochemical interactions with the environment and/or counterbody, and changes in the material's structure (phase transformations). The former ones have been studied by mechanical engineers and tribologists, but the processes of phase transformations at the sharp contact have only been investigated for a very few materials (silicon is one of them) and further research is necessary. One of the reasons for the lack of information may be the fact that the problem is at the interface between at least three scientific fields, that is, materials science, mechanics, and solid state physics. Thus, an interdisciplinary approach is required to solve this problem and understand how and why a hydrostatic or shear stress in the two-body contact can drive phase transformations in materials.
Echocardiographic Risk Factors for Stroke and Outcomes in Patients With Atrial Fibrillation Anticoagulated With Apixaban or Warfarin

Background and Purpose— Few data exist on the long-term outcomes of patients with spontaneous echo contrast (SEC), left atrial/left atrial appendage (LA/LAA) thrombus, and complex aortic plaque (CAP), in patients with atrial fibrillation receiving oral anticoagulation. We explored the relationship between these 3 echocardiographic findings and clinical outcomes, and the comparative efficacy and safety of apixaban and warfarin for each finding. Methods— Patients from the ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) with SEC, LA/LAA thrombus, or CAP diagnosed by either transthoracic or transesophageal echocardiography were compared with patients with none of these findings on transesophageal echocardiography. Results— A total of 1251 patients were included: 217 had SEC, 127 had LA/LAA thrombus, 241 had CAP, and 746 had none. The rates of stroke/systemic embolism were not significantly different among patients with and without these echocardiographic findings (hazard ratio, 0.96; 95% confidence interval, 0.25–3.60 for SEC; hazard ratio, 1.27; 95% confidence interval, 0.23–6.86 for LA/LAA thrombus; hazard ratio, 2.21; 95% confidence interval, 0.71–6.85 for CAP). Rates of ischemic stroke, myocardial infarction, cardiovascular death, and all-cause death were also not different between patients with and without these findings. For patients with either SEC or CAP, there was no evidence of a differential effect of apixaban over warfarin. For patients with LA/LAA thrombus, there was also no significant interaction, with the exception of all-cause death and any bleeding where there was a greater benefit of apixaban compared with warfarin among patients with no LA/LAA thrombus. Conclusions— In anticoagulated patients with atrial fibrillation and risk factors for stroke, echocardiographic findings do not seem to add to the risk of thromboembolic events. Clinical Trial Registration— URL: http://www.clinicaltrials. gov. Unique identifier: NCT00412984.
The position of Ghana on the progressive map of positive mental health: A critical perspective

ABSTRACT According to the World Health Organisation (WHO), mental health is a state of well-being and not just the absence of diseases. With this definition, there has been a surge of mental health research, albeit still predominantly in Western countries, which is reflected in contemporary theories on positive mental health that include ‘flourishing mental health’, ‘salutogenesis’, and ‘fortigenesis’. However, in low- and middle-income countries (LMICs), mental health research is slowly receiving scholarly attention. The aim of this paper was twofold: Firstly, to highlight progress that had been made in some LMICs, giving consideration to research across different settings and populations as a basis to argue for more research on positive mental health in the Ghanaian context. Secondly, to present a critical perspective on the current mental health research trends in Ghana, thus discussing important recommendations for future research.
Common germline haplotypes and genotypes identified in BRCA2 exon 11 of dogs with mammary tumours and histopathological analyses

The canine BRCA2 is a tumor supressor gene which encodes the BRCA2 protein, involved in DNA repair through interaction with the RAD51 recombinase. This process is mediated by eigth BRC repeats that are encoded by BRCA2 exon 11. Two variants corresponding to human mutations in human BRC3 repeat have been reported in canine BRC3 repeat. In addition, other variants have also been described in canine BRCA2 exon 11. Considering the importance of polymorphisms in human BRCA2 to breast cancer development, this study aimed to investigate the frequency of variants in BRCA2 exon 11 in 48 blood and tissue DNA samples from bitches with canine mammary tumors (CMT), as well as, to analyze tumor stage and histopathological features. Seven Single Nucleotide Polymorphisms (SNPs) were identified, three of which were evaluated as possibily or probably deleterious variant. Interestingly, almost all the 22 mammary tumors (except one) which presented a clinical staging equal to or greater than III carried at least one mutant allele of these three variants. Besides that, no statistically significant correlation was observed between any of the reported SNPs in heterozygosis or homozygosis and either dogs data (such as breed, age or disease stage) or mammary tumors histopathological characteristics. A total of 97.9% of bitches had one to three polymorphisms of the seven identified in this study, which suggests a possibly correlation between the canine BRCA2 exon 11 polymorphisms and mammary carcinogenesis.