Miracle-dz/UniFAR-FTUs huggingface dataset:
Cardiac myosin binding protein-C phosphorylation regulates the super-relaxed state of myosin

Significance Cardiac myosin binding protein-C (cMyBP-C) is a sarcomeric protein closely linked to cardiac contractility. Importantly, although the phosphorylation status of cMyBP-C regulates the force and rate of cardiac contraction, the exact molecular mechanism(s) remain(s) unclear. Previously, loss of, or mutations in, cMyBP-C resulted in a loss of the inhibited super-relaxed state (SRX) of myosin, which explains the hypercontractile phenotype. Thus, we asked if cMyBP-C phosphorylation would increase contractile function by the release of myosin heads from SRX to a state more conducive to their interaction with actin. We found that a site-specific, phosphorylation-dependent interaction between cMyBP-C and myosin does modulate the fraction of SRX myosin that controls contractility. Phosphorylation of cardiac myosin binding protein-C (cMyBP-C) accelerates cardiac contractility. However, the mechanisms by which cMyBP-C phosphorylation increases contractile kinetics have not been fully elucidated. In this study, we tested the hypothesis that phosphorylation of cMyBP-C releases myosin heads from the inhibited super-relaxed state (SRX), thereby determining the fraction of myosin available for contraction. Mice with various alanine (A) or aspartic acid (D) substitutions of the three main phosphorylatable serines of cMyBP-C (serines 273, 282, and 302) were used to address the association between cMyBP-C phosphorylation and SRX. Single-nucleotide turnover in skinned ventricular preparations demonstrated that phosphomimetic cMyBP-C destabilized SRX, whereas phospho-ablated cMyBP-C had a stabilizing effect on SRX. Strikingly, phosphorylation at serine 282 site was found to play a critical role in regulating the SRX. Treatment of WT preparations with protein kinase A (PKA) reduced the SRX, whereas, in nonphosphorylatable cMyBP-C preparations, PKA had no detectable effect. Mice with stable SRX exhibited reduced force production. Phosphomimetic cMyBP-C with reduced SRX exhibited increased rates of tension redevelopment and reduced binding to myosin. We also used recombinant myosin subfragment-2 to disrupt the endogenous interaction between cMyBP-C and myosin and observed a significant reduction in the population of SRX myosin. This peptide also increased force generation and rate of tension redevelopment in skinned fibers. Taken together, this study demonstrates that the phosphorylation-dependent interaction between cMyBP-C and myosin is a determinant of the fraction of myosin available for contraction. Furthermore, the binding between cMyBP-C and myosin may be targeted to improve contractile function.
Business Model Transformation in Moving to a Cross-Channel Retail Strategy: A Case Study

Although cross-channel retailing has become a game changer for retailers, few previous studies have looked at the problems from the inherently holistic perspective of a business model approach. Using a single case study but multiple data collection methods, including interviews, observations, and document analysis, on the biggest Chinese retailer in consumer electronic appliances, the present study examines how different aspects of the business model changed after the retailer launched its cross-channel strategy. The results identify the major changes on three fronts: redefinition of target clients, a new proposition for shopping value, and redesign of the value chain. Findings suggest that a retailer shifting toward the cross-channel strategy will follow the stage-of-adoption model, which may be in five stages, and that the physical store as a hub linking different channels will become the source of value creation. To facilitate the strategic shift, retailers should optimize rather than merge their activities across channels, reinforce the strengths of the physical store, develop co-creation value with stakeholders, and revamp their organization.
Evaluation of a New Chromogenic Medium (StrepB Select) for Detection of Group B Streptococcus from Vaginal-Rectal Specimens

ABSTRACT We compared StrepB Select medium (Select) after enrichment with conventional culture for the detection of Group B Streptococcus (GBS). Postenrichment sensitivities of Select and conventional culture were 98.8% and 92.2%, respectively (P < 0.05). Select was superior for detection of GBS from vaginal-rectal specimens. Growth of non-GBS colonies required additional work to exclude the presence of GBS, especially after 48 h of incubation. Incubation of Select beyond 24 h did not significantly increase the yield of GBS.
Ssd1 and the cell wall integrity pathway promote entry, maintenance, and recovery from quiescence in budding yeast

Wild Saccharomyces cerevisiae strains are typically diploid. When faced with glucose and nitrogen limitation they can undergo meiosis and sporulate. Diploids can also enter a protective, nondividing cellular state or quiescence. The ability to enter quiescence is highly reproducible but shows broad natural variation. Some wild diploids can only enter cellular quiescence, which indicates that there are conditions in which sporulation is lost or selected against. Others only sporulate, but if sporulation is disabled by heterozygosity at the IME1 locus, those diploids can enter quiescence. W303 haploids can enter quiescence, but their diploid counterparts cannot. This is the result of diploidy, not mating type regulation. Introduction of SSD1 to W303 diploids switches fate, in that it rescues cellular quiescence and disrupts the ability to sporulate. Ssd1 and another RNA-binding protein, Mpt5 (Puf5), have parallel roles in quiescence in haploids. The ability of these mutants to enter quiescence, and their long-term survival in the quiescent state, can be rescued by exogenously added trehalose. The cell wall integrity pathway also promotes entry, maintenance, and recovery from quiescence through the Rlm1 transcription factor.
New findings of Setaria tundra and Setaria cervi in the red deer (Cervus elaphus) in Poland

Abstract Our study aimed at examining the phylogenetic position of the newly-found Setaria nematodes obtained from the red deer (Cervus elaphus) based on sequences of the mitochondrial cytochrome c oxidase subunit 1 (COX-1). Alignment and phylogenetic analyses, as well as SEM microscopic analysis, revealed the presence of two Setaria species: S. cervi and S. tundra. Setaria tundra was noted in only one individual, a calf of the red deer, while S. cervi was observed in three stages, two hinds and one calf of the red deer. According to our knowledge, it is the first case of S. cervi in the red deer in Poland confirmed in molecular studies and also the first case of S. tundra infection in the red deer.
Laser- and cryogenic probe-assisted NMR enables hypersensitive analysis of biomolecules at submicromolar concentration

Significance Despite its prominent role in structural biology, NMR spectroscopy is hampered by extremely poor sensitivity. In this work, we develop a laser-assisted methodology, LC-photo-CIDNP, to enhance NMR sensitivity for the detection of amino acids and proteins in solution down to nanomolar concentration. Our method is significant because it enables detection of nanomolar concentrations of aromatic amino acids (Trp and Tyr), either in their free state or within proteins, in only a few seconds. Hence, the LC-photo-CIDNP approach renders data collection thousands of times faster than laser-free NMR experiments performed on higher-field spectrometers. Further, LC-photo-CIDNP is readily applicable to both 1D and 2D data collection mode. Rapid detection of proteins in solution at nanomolar concentration by NMR spectroscopy is unprecedented. Solution-state NMR typically requires 100 μM to 1 mM samples. This limitation prevents applications to mass-limited and aggregation-prone target molecules. Photochemically induced dynamic nuclear polarization was adapted to data collection on low-concentration samples by radiofrequency gating, enabling rapid 1D NMR spectral acquisition on aromatic amino acids and proteins bearing aromatic residues at nanomolar concentration, i.e., a full order of magnitude below other hyperpolarization techniques in liquids. Both backbone H1-C13 and side-chain resonances were enhanced, enabling secondary and tertiary structure analysis of proteins with remarkable spectral editing, via the 13C PREPRINT pulse sequence. Laser-enhanced 2D NMR spectra of 5 μM proteins at 600 MHz display 30-fold better S/N than conventional 2D data collected at 900 MHz. Sensitivity enhancements achieved with this technology, denoted as low-concentration photo-CIDNP (LC-photo-CIDNP), depend only weakly on laser intensity, highlighting the opportunity of safer and more cost-effective hypersensitive NMR applications employing low-power laser sources.
Fluid Restriction Decreases Solid Food Consumption Post-Exercise

Dehydration in rodents induces anorexia. In humans however, the role of dehydration in energy intake is controversial. This study investigated the effect of extreme fluid restriction on acute energy intake during and after exercise-induced dehydration. Eight physically active participants performed two exercise sessions to induce dehydration. After the exercise, the men were allowed to either rehydrate for 2 h or were maintained in a hypohydrated state, in a randomized manner. After 2 h, they were given cereal bars ad libitum for 1 h. Blood and saliva samples of the participants were collected before the exercise session, after the exercise session, after rehydration, and after the meal. Post-exercise energy intake differed between hypohydrated (1430 ± 210 kcal) and rehydrated (2190 ± 780 kcal) trials (p = 0.01). For the concentrations of ghrelin and leptin, there were no significant effects of time (p = 0.94, p = 0.21), between trials (p = 0.09, p = 0.99), or due to a trial–time interaction (p = 0.64, p = 0.68), respectively. The concentrations of peptide YY (PYY) were not different between trials (p = 0.94) but there was a significant effect of time (p = 0.0001) and a trial–time interaction (p = 0.01), with higher levels in the rehydration trial after eating in response to a higher energy intake. For saliva production, there was a significant effect of time (p = 0.02) and a trial–time interaction (p = 0.04), but no between-trial effect (p = 0.08). In conclusion, extreme fluid restriction decreased acute food intake after exercise, which may be explained by a lower flow of saliva.
Bat flies aggregation on Artibeus planirostris hosts in the Pantanal floodplain and surrounding plateaus

Abstract For parasites in natural systems, the most common pattern of spatial distribution is aggregation among hosts. The main causes of such aggregation are variable exposure of hosts to parasites and heterogeneity in host susceptibility. The objective of this study was to determine if there are differences in the aggregation pattern of two species of ectoparasitic flies between the Pantanal and Cerrado regions of Brazil on the bat Artibeus planirostris. We collected the ectoparasites from bats captured between 2002 and 2017 with mist nets in 21 sites in the Pantanal and 15 sites in the surrounding plateaus. The results showed that the aggregation of ectoparasitic flies in Pantanal was more pronounced than in Cerrado. The discrepancy aggregation index (D) of the bat fly Megistopoda aranea was 0.877 in Pantanal and 0.724 in Cerrado. The D values of Aspidoptera phyllostomatis was even higher, with 0.916 and 0.848 in the Pantanal and Cerrado, respectively. Differences in the shelters used may be the main factor shaping variation in aggregation, since the Pantanal does not have rock formations, with only foliage, crowns and hollow tree trunks. These differences likely affect host exposure to the parasites, leading to an increase in parasite aggregation.
Association of RAGE gene multiple variants with the risk for COPD and asthma in northern Han Chinese

Clinical and experimental data have shown that the receptor for advanced glycation end products (RAGE) is implicated in the pathogenesis of respiratory disorders. In this study, we genotyped five widely-evaluated variants in RAGE gene, aiming to assess their association with the risk for chronic obstructive pulmonary disease (COPD) and asthma in northern Han Chinese. Genotypes were determined in 105 COPD patients, 242 asthma patients and 527 controls. In single-locus analysis, there was significant difference in the genotype distributions of rs1800624 between COPD patients and controls (p=0.022), and the genotype and allele distributions of rs1800625 differed significantly (p=0.040 and 0.016) between asthma patients and controls. Haplotype analysis revealed that haplotype T-A-G-T (allele order: rs1800625, rs1800624, rs2070600, rs184003) was significantly associated with a reduced COPD risk (OR=0.32, 95% CI: 0.06-0.60), and haplotype T-A-A-G was significantly associated with a reduced asthma risk (OR=0.19, 95% CI: 0.04-0.96). Further haplotype-phenotype analysis showed that high- and low-density lipoprotein cholesterol and blood urea nitrogen were significant mediators for COPD (psim=0.041, 0.043 and 0.030, respectively), and total cholesterol was a significant mediator for asthma (psim=0.009). Taken together, our findings indicate that RAGE gene is a promising candidate for COPD and asthma, and importantly both disorders are genetically heterogeneous.
Multiple Antibiotic Resistance (MAR), Plasmid Profiles, and DNA Polymorphisms among Vibrio vulnificus Isolates

Sixty strains (n = 60) of Vibrio vulnificus were examined for their multiple antibiotic resistance (MAR) index, plasmid profiles, and DNA polymorphisms. Thirty-seven strains (n = 37) were isolated from cockles (Anadara granosa) in Malaysia, while 23 (n = 23) isolates were isolated from clams (Mercenaria mercenaria) in Qatar. All isolates were resistant to two or more of the antibiotics tested, with the most common resistances were demonstrated towards penicillin (93%), ampicillin (70%), cephalothin (65%), clindamycin (66%), vancomycin (64%), and erythromycin (51%). The antibiotic that experienced the least resistance was kanamycin (6%), and all isolates were susceptible to cefoperazone, streptomycin, and tetracycline. The MAR index for the V. vulnificus isolated from Malaysia and Qatar, possessed similar values which ranged from 0.2 to 0.7, respectively. Plasmid analysis demonstrated that 65% of V. vulnificus strains harbored plasmids, while 35% were not. Nineteen (P1–P19) plasmids profiles were observed. No specific cluster or group was observed although they were isolated from different sample sources and locations by phylogenetic analysis using GelCompar II software at an 80% similarity level. Results demonstrated the high MAR index and genomic heterogeneity of V. vulnificus, which are of great concern to the human health of those who have consumed cockles and clams from the study area.
Definitions of sex and intimacy among gender and sexual minoritised groups in urban India

Abstract Understandings of sex and intimacy carry important implications for individuals’ behaviours and health. In many research studies, sex is narrowly defined as penile-vaginal intercourse, which may exclude the experiences of sexual and gender minoritised individuals. Likewise, sexual intimacy, or intimacy related to sexual experience between two or more people, is under-researched. Even less is known about how sexual and gender minoritised individuals in countries such as India understand these concepts. This qualitative study included focus group discussions and interviews conducted in three urban areas in India – Chennai, Bangalore and Kolkata. Data were analysed thematically. Participants described sex as a context-dependent experience, acknowledging that their definitions might not capture others’ characterisations. Participants reported numerous barriers to intimacy, especially for transgender and other gender minority individuals. We discuss the implications of simplistic definitions related to gender and sexuality for future sexuality research and public health in settings such as those discussed here.
Role of Vessel Microstructure in the Longevity of End-to-side Grafts.

Compliance mismatch between the graft and the host artery of an end-to-side (ETS) arterial bypass graft increases the intramural stress in the ETS graft-artery junction, and thus may compromise its long-term patency. The present study takes into account the effects of collagen fibers to demonstrate how their orientations alter the stresses. The stresses in a bypass graft, as a man-made bifurcation, are compared to those of its natural counterparts with different fiber orientations. The results indicate that the fiber orientation mismatch between the graft and the host artery may increase the stresses at both the heel and toe regions of the ETS anastomosis (the maximum principal stress at the heel and toe regions increased by 72 and 12%, respectively). Our observations, thus, propose that the mismatch between the collagen fiber orientations of the graft and the host artery, independent of the effect of the suture line, may induce aberrant stresses to the anastomosis of the bypass graft.
Induction of the human protein P56 by interferon, double-stranded RNA, or virus infection.

P56 is the most abundant protein induced by interferon (IFN) treatment of human cells. To facilitate studies on its induction pattern and cellular functions, we expressed recombinant P56 as a hexahistidine-tagged protein in Escherichia coli and purified it to apparent homogeneity using affinity chromatography. A polyclonal antibody raised against this recombinant protein was used to show that P56 is primarily a cytoplasmic protein. Cellular expression of P56 by transfection did not inhibit the replication of vesicular stomatitis virus and encephalomyocarditis virus. P56 synthesis was rapidly induced by IFN-beta, and the protein had a half-life of 6 h. IFN-gamma or poly(A)(+) could not induce the protein, but poly(I)-poly(C) or an 85-bp synthetic double-stranded RNA efficiently induced it. Similarly, infection of GRE cells, which are devoid of type I IFN genes, by vesicular stomatitis virus, encephalomyocarditis virus, or Sendai virus caused P56 induction. Surprisingly, Sendai virus could also induce P56 in the mutant cell line P2.1, which cannot respond to either IFN-alpha/beta or double-stranded RNA. Induction of P56 in the P2.1 cells and the parental U4C cells by virus infection was preceded by activation of IRF-3 as judged by its translocation to the nucleus from the cytoplasm.
Wearable Embedded Intelligence for Detection of Falls Independently of on-Body Location

Falls are one of the most common problems in the elderly population. Therefore, each year more solutions for automatic fall detection are emerging. This paper proposes a single accelerometer algorithm for wearable devices that works for three different body locations: chest, waist and pocket, without a calibration step being required. This algorithm is able to be fully executed on a wearable device and no external devices are necessary for data processing. Additionally, a study of the accelerometer sampling rate, that allows the algorithm to achieve a better performance, was performed. The algorithm was validated with a continuous dataset with daily living activities and 272 simulated falls. Considering the trade-off between sensitivity and the number of false alarms the most suitable sampling rate found was 50 Hz. The proposed algorithm was able to achieve a trade-off of no false alarms and 89.5% of fall detection rate when wearing the sensor on the user’s waist with a medium sensitivity level of the algorithm. In conclusion, this paper presents a reliable solution for automatic fall detection that can be adapted to different usages and conditions, since it can be used in different body locations and its sensitivity can be adapted to different subjects according to their physical activity level.
A critical time window for recovery extends beyond one-year post-stroke

The impact of rehabilitation on post-stroke motor recovery and its dependency on the patient’s chronicity remain unclear. The field has widely accepted the notion of a proportional recovery rule with a “critical window for recovery” within the first 3–6 mo poststroke. This hypothesis justifies the general cessation of physical therapy at chronic stages. However, the limits of this critical window have, so far, been poorly defined. In this analysis, we address this question, and we further explore the temporal structure of motor recovery using individual patient data from a homogeneous sample of 219 individuals with mild to moderate upper-limb hemiparesis. We observed that improvement in body function and structure was possible even at late chronic stages. A bootstrapping analysis revealed a gradient of enhanced sensitivity to treatment that extended beyond 12 mo poststroke. Clinical guidelines for rehabilitation should be revised in the context of this temporal structure. NEW & NOTEWORTHY Previous studies in humans suggest that there is a 3- to 6-mo “critical window” of heightened neuroplasticity poststroke. We analyze the temporal structure of recovery in patients with hemiparesis and uncover a precise gradient of enhanced sensitivity to treatment that expands far beyond the limits of the so-called critical window. These findings highlight the need for providing therapy to patients at the chronic and late chronic stages.
A preliminary test of a brief intervention to lessen young adults' cannabis use: Episode-level smartphone data highlights the role of protective behavioral strategies and exercise.

Brief interventions are increasingly being used to help young adults to moderate their cannabis use. We conducted a randomized clinical trial of a brief (4 weekly sessions), in-person intervention that included a smartphone application that reinforced the use of protective behavioral strategies (PBSs) to lessen cannabis use. Young adults (N = 37; 24 men) who regularly used cannabis were randomized to 2 intervention conditions rooted in cognitive-behavioral therapy (CBT) and motivational enhancement therapy (MET). Along with learning CBT + MET strategies, participants in 1 of the conditions were instructed to engage in exercise. All participants used smartphone-based ecological momentary assessment to provide episode-level reports about use of cannabis and PBSs. Two multilevel structural equation models were run to test the study hypotheses that (a) cannabis use would be reduced over the course of the 6-month study, (b) reductions would be moderated by intervention condition, and (c) episode-level PBS use would predict episode-level cannabis use. Participants reduced their cannabis use by approximately 1 half of a standard joint per time point. The MET + CBT + Exercise condition reduced cannabis use to a greater degree than did the MET + CBT condition. With episode-level PBS use in the model, reductions in cannabis use were independent of intervention condition. Our findings suggest that young adults will engage with a smartphone app that serves as a component of an in-person intervention to moderate their cannabis use. Intervention content that promotes the use of PBSs and exercise facilitates reductions in cannabis use. (PsycINFO Database Record (c) 2019 APA, all rights reserved).