Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic variability of human respiratory syncytial virus group B in Panama reveals a novel genotype BA14

In Panama, human respiratory syncytial virus (HRSV) is responsible of 20‐40% of acute respiratory infections in children under 5 years old. Currently, little is known about the genetic variability of HRSV in Central America and the Caribbean. Recently, we reported the genetic variability of HRSV‐A, however; no studies on HRSV‐B in Panama have been described yet. In this study, 24 sequences of Panamanian HRSV‐B, from children (<5 years) with acute respiratory infections (ARI), collected from July 2008 to November 2012 were analyzed. All sequences share the characteristic 60‐nt duplication of the BA strains. Six Panamanian strains grouped with the BA10 genotype and 12 samples clustered together in a separate monophyletic clade with an aLRT support value of 0.92 and an intra‐group p‐distance less than 0.07. This fulfills the criteria to consider a new genotype in HRSV, which we named BA14 genotype. Another six strains remain unclassified, but closely related to BA9, BA11, or the new BA14 genotypes, according to their genetic p‐distance. Different amino acid substitutions in the Panamanian HRSV‐B strains were observed, some previously described and others found only on Panamanian strains. This study contributes to the knowledge of the genetic variability and evolution of HRSV in Central America.
Inhibition of TLR2 signaling by small molecule inhibitors targeting a pocket within the TLR2 TIR domain

Significance Excess Toll-like receptor 2 (TLR2) signaling has been implicated in numerous inflammatory diseases, yet there is no TLR2 inhibitor licensed for human use. Using computer-aided drug design (CADD), we identified a compound, C16H15NO4 (C29), and a derivative, ortho-vanillin, that inhibit TLR2 signaling in vitro and in vivo. Our findings also revealed unexpected differences between TLR2/1 and TLR2/6 signaling in mice vs. humans. Importantly, our data provide proof of principle that the CADD-targeted BB loop pocket residues are critical for TLR2 signaling and may be targeted therapeutically. Toll-like receptor (TLR) signaling is initiated by dimerization of intracellular Toll/IL-1 receptor resistance (TIR) domains. For all TLRs except TLR3, recruitment of the adapter, myeloid differentiation primary response gene 88 (MyD88), to TLR TIR domains results in downstream signaling culminating in proinflammatory cytokine production. Therefore, blocking TLR TIR dimerization may ameliorate TLR2-mediated hyperinflammatory states. The BB loop within the TLR TIR domain is critical for mediating certain protein–protein interactions. Examination of the human TLR2 TIR domain crystal structure revealed a pocket adjacent to the highly conserved P681 and G682 BB loop residues. Using computer-aided drug design (CADD), we sought to identify a small molecule inhibitor(s) that would fit within this pocket and potentially disrupt TLR2 signaling. In silico screening identified 149 compounds and 20 US Food and Drug Administration-approved drugs based on their predicted ability to bind in the BB loop pocket. These compounds were screened in HEK293T-TLR2 transfectants for the ability to inhibit TLR2-mediated IL-8 mRNA. C16H15NO4 (C29) was identified as a potential TLR2 inhibitor. C29, and its derivative, ortho-vanillin (o-vanillin), inhibited TLR2/1 and TLR2/6 signaling induced by synthetic and bacterial TLR2 agonists in human HEK-TLR2 and THP-1 cells, but only TLR2/1 signaling in murine macrophages. C29 failed to inhibit signaling induced by other TLR agonists and TNF-α. Mutagenesis of BB loop pocket residues revealed an indispensable role for TLR2/1, but not TLR2/6, signaling, suggesting divergent roles. Mice treated with o-vanillin exhibited reduced TLR2-induced inflammation. Our data provide proof of principle that targeting the BB loop pocket is an effective approach for identification of TLR2 signaling inhibitors.
Abundance and Size Distribution of the Sacoglossan Elysia viridis on Co-Occurring Algal Hosts on the Swedish West Coast

Sacoglossans are specialized marine herbivores that tend to have a close evolutionary relationship with their macroalgal hosts, but the widely distributed species Elysia viridis can associate with several algal species. However, most previous investigations on the field abundance and size distribution of E. viridis have focussed on Codium spp. in the British Isles, and algae from this genus are considered superior hosts for E. viridis. In the present study, we investigated the abundance and size distribution of E. viridis on 6 potential host algae with differing morphologies (the septate species Cladophora sericea, Cladophora rupestris, Chaetomorpha melagonium, and Ceramium virgatum, as well as the siphonaceous species Codium fragile and Bryopsis sp.) at 2 sites on the Swedish west coast over the course of a year. In spring, slugs were almost absent from all algal hosts. In summer and autumn, E. viridis consistently occurred on several of the algal species at both sites. The highest number of small E. viridis were found on C. sericea, intermediate numbers of significantly larger E. viridis were found on C. rupestris, while fewer, intermediate sized animals were found on C. fragile. Throughout the study period, only a few E. viridis individuals were found on C. melagonium, Bryopsis sp. , and C. virgatum. Our results indicate that E. viridis is an annual species in Sweden, capable of exploiting co-occurring congeneric and intergeneric algal hosts with differing morphologies. These results corroborate previous findings that E. viridis can exploit several different algal species, but does not indicate that C. fragile is a superior host.
Structural Characterization of the Saccharomyces cerevisiae THO Complex by Small-Angle X-Ray Scattering

The THO complex participates during eukaryotic mRNA biogenesis in coupling transcription to formation and nuclear export of translation-competent messenger ribonucleoprotein particles. In Saccharomyces cerevisiae, THO has been defined as a heteropentamer composed of the Tho2p, Hpr1p, Tex1p, Mft1p, and Thp2p subunits and the overall three-dimensional shape of the complex has been established by negative stain electron microscopy. Here, we use small-angle X-ray scattering measured for isolated THO components (Mft1p and Thp2p) as well as THO subcomplexes (Mft1p-Thp2p and Mft1p-Thp2p-Tho2p) to construct structural building blocks that allow positioning of each subunit within the complex. To accomplish this, the individual envelopes determined for Mft1p and Thp2p are first fitted inside those of the Mft1p-Thp2p and Mft1p-Thp2p-Tho2p complexes. Next, the ternary complex structure is placed in the context of the five-component electron microscopy structure. Our model reveals not only the position of each protein in the THO complex relative to each other, but also shows that the pentamer is likely somewhat larger than what was observed by electron microscopy.
Association Between Mental Health Status and Patient Satisfaction With the Functional Outcomes of Rhinoplasty

Importance Mental health can have an impact on patient satisfaction with rhinoplasty. However, the association between mental health and patient satisfaction with functional outcomes of rhinoplasty is poorly understood. Objective To determine whether preoperative mental health is associated with satisfaction with functional outcomes of rhinoplasty. Design, Setting, and Participants This case-control study assessed baseline nasal function and postsurgical functional outcomes for 88 consecutive patients undergoing rhinoplasty with both cosmetic and functional goals at 2 tertiary rhinologic centers in Sydney, Australia. Exposures Poor mental well-being was defined preoperatively by the Optum SF-36v2 Health Survey mental component summary. Main Outcomes and Measures Nasal function was assessed with patient-reported outcome measures, including visual analog scales, the Nasal Obstruction Symptom Evaluation Scale (NOSE), the 22-item Sinonasal Outcome Test (SNOT-22), and Likert scales. Objective outcomes included nasal peak inspiratory flow, nasal airway resistance, and minimum cross-sectional area. All outcomes were assessed preoperatively and 6 months postoperatively. The 36-item Optum SF-36v2 Health Survey mental component summary was used to assess mental well-being, with a score of less than 40 indicating poor mental well-being and a score 40 or higher indicating normal well-being. Results Mean (SD) patient age was 37.6 (12.9) years and 53 of 88 (60.2%) were women. The mental component summary defined impaired well-being in n = 24 (cases) and normal well-being in n = 64 (controls). There were improvements in the total study population across most nasal function outcomes and in both groups. After rhinoplasty, benefit was seen for both groups in visual analog scale (left side mean [SD] change, 18 [30]; P < .001 and right side mean [SD] change, 24 [30]; P < .001); NOSE (mean [SD] change, 1.35 [1.21]; P < .001); and SNOT-22 (mean [SD] change, 0.81 [0.88]; P < .001) scores. Nasal peak inspiratory flow improved for both groups (mean [SD] change, 32 [45] L/min; P < .001), while nasal airway resistance and minimum cross-sectional area remained similar (change in nasal airway resistance, 0.086 Pa/cm3/s; 95% CI, −0.007 Pa/cm3/s to 0.179 Pa/cm3/s and change in minimum cross-sectional area, −0.04 cm2; 95% CI, −0.21 cm2 to 0.13 cm2). Patients with poor mental health had similar improvements in nasal function compared with controls. Conclusions and Relevance Rhinoplasty imparts similar benefits to nasal function assessed by patient-reported outcome measures and objective airflow measures regardless of preoperative mental health status. Level of Evidence 3.
A mechanism for elbow exoskeleton for customised training

It is well proven that repetitive extensive training consisting of active and passive therapy is effective for patients suffering from neuromuscular deficits. The level of difficulty in rehabilitation should be increased with time to improve the neurological muscle functions. A portable elbow exoskeleton has been designed that will meet these requirements and potentially offers superior outcomes than human-assisted training. The proposed exoskeleton can provide both active and passive rehabilitation in a single structure without changing its configuration. The idea is to offer three levels of rehabilitation; namely active, passive and stiffness control in a single device using a single actuator. The mechanism also provides higher torque to weight ratio making it an energy efficient mechanism.
Impact of Type of Sport, Gender and Age on Red Blood Cell Deformability of Elite Athletes

Abstract Our objective was to detect possible differences in red blood cell (RBC) deformability of elite athletes performing different types of sports and being of different age and gender.182 athletes were included in this cross-sectional study. RBC deformability was measured using the laser-assisted optical rotational cell-analyzer. Maximal elongation index (EI max) and shear stress at half-maximum deformation (SS 1/2) were calculated. The ratio SS 1/2 /EI max (EI Ratio) was calculated with low values representing high RBC deformation. Hematocrit (Hct) and mean cellular volume (MCV) were determined in venous blood. Overall RBC deformability did not differ between male and female athletes but, when separated by age of the subjects, RBC deformability increased with age in male but not in female athletes. RBC deformability was lower in Combat sports compared other sport groups. Hct was higher in male compared to female athletes while no difference was observed for MCV. MCV and Hct increased with increasing age. A negative correlation was found between the EI Ratio and MCV and between EI Ratio and Hct. Conclusion: RBC deformability is influenced by age and endurance rate of the sport which suggests that the RBC system may adapt to changing conditions such as adolescence with the onset effects of sex hormones or physical exercise.
SEVEN Dynamic patterns of adaptive radiation : evolution of mating preferences sergey gavrilets and aaron vose

Introduction Adaptive radiation is defined as the evolution of ecological and phenotypic diversity within a rapidly multiplying lineage (Simpson 1953; Schluter 2000). Examples include the diversification of Darwin’s finches on the Galápagos islands, Anolis lizards on Caribbean islands, Hawaiian silverswords, a mainland radiation of columbines, and cichlids of the East African Great Lakes, among many others (Simpson 1953; Givnish & Sytsma 1997; Losos 1998; Schluter 2000; Gillespie 2004; Salzburger & Meyer 2004; Seehausen 2006). Adaptive radiation typically follows the colonization of a new environment or the establishment of a ‘key innovation’ (e.g. nectar spurs in columbines, Hodges 1997) which opens new ecological niches and/or new paths for evolution. Adaptive radiation is both spectacular and a remarkably complex process, which is affected by many different factors (genetical, ecological, developmental, environmental, etc.) interweaving in non-linear ways. Different, sometimes contradictory scenarios explaining adaptive radiation have been advanced (Simpson 1953; Mayr 1963; Schluter 2000). Some authors emphasize random genetic drift in small founder populations (Mayr 1963), while others focus on strong directional selection in small founder populations (Eldredge 2003; Eldredge et al. 2005), strong diversifying selection (Schluter 2000), or relaxed selection (Mayr 1963). Identifying the more plausible and general scenarios is a highly controversial endeavour. The large timescale involved and the lack of precise data on its initial and intermediate stages evenmake identifying general patterns of adaptive radiation very difficult (Simpson 1953; Losos 1998; Schluter 2000; Gillespie 2004; Salzburger & Meyer 2004; Seehausen 2006). Further, it is generally unknown if the patterns identified in specific case studies apply to other systems. The difficulties in empirical studies of general patterns of adaptive radiation, its timescales, driving forces, and consequences for the formation of biodiversity make theoretical approaches important. Perhaps surprisingly, the phenomenon of adaptive radiation remains largely unexplored from a theoretical modelling perspective. Adaptive radiation can be viewed as an extension of
Optogenetic Demonstration of Functional Innervation of Mouse Colon by Neurons Derived From Transplanted Neural Cells.

BACKGROUND & AIMS Cell therapy offers the potential to treat gastrointestinal motility disorders caused by diseased or absent enteric neurons. We examined whether neurons generated from transplanted enteric neural cells provide a functional innervation of bowel smooth muscle in mice. METHODS Enteric neural cells expressing the light-sensitive ion channel, channelrhodopsin, were isolated from the fetal or postnatal mouse bowel and transplanted into the distal colon of 3- to 4-week-old wild-type recipient mice. Intracellular electrophysiological recordings of responses to light stimulation of the transplanted cells were made from colonic smooth muscle cells in recipient mice. Electrical stimulation of endogenous enteric neurons was used as a control. RESULTS The axons of graft-derived neurons formed a plexus in the circular muscle layer. Selective stimulation of graft-derived cells by light resulted in excitatory and inhibitory junction potentials, the electrical events underlying contraction and relaxation, respectively, in colonic muscle cells. Graft-derived excitatory and inhibitory motor neurons released the same neurotransmitters as endogenous motor neurons-acetylcholine and a combination of adenosine triphosphate and nitric oxide, respectively. Graft-derived neurons also included interneurons that provided synaptic inputs to motor neurons, but the pharmacologic properties of interneurons varied with the age of the donors from which enteric neural cells were obtained. CONCLUSIONS Enteric neural cells transplanted into the bowel give rise to multiple functional types of neurons that integrate and provide a functional innervation of the smooth muscle of the bowel wall. Circuits composed of both motor neurons and interneurons were established, but the age at which cells are isolated influences the neurotransmitter phenotype of interneurons that are generated.
Sensitivity Analyses for Robust Causal Inference from Mendelian Randomization Analyses with Multiple Genetic Variants

Mendelian randomization investigations are becoming more powerful and simpler to perform, due to the increasing size and coverage of genome-wide association studies and the increasing availability of summarized data on genetic associations with risk factors and disease outcomes. However, when using multiple genetic variants from different gene regions in a Mendelian randomization analysis, it is highly implausible that all the genetic variants satisfy the instrumental variable assumptions. This means that a simple instrumental variable analysis alone should not be relied on to give a causal conclusion. In this article, we discuss a range of sensitivity analyses that will either support or question the validity of causal inference from a Mendelian randomization analysis with multiple genetic variants. We focus on sensitivity analyses of greatest practical relevance for ensuring robust causal inferences, and those that can be undertaken using summarized data. Aside from cases in which the justification of the instrumental variable assumptions is supported by strong biological understanding, a Mendelian randomization analysis in which no assessment of the robustness of the findings to violations of the instrumental variable assumptions has been made should be viewed as speculative and incomplete. In particular, Mendelian randomization investigations with large numbers of genetic variants without such sensitivity analyses should be treated with skepticism.
Drought stress differentially regulates the expression of small open reading frames (sORFs) in Arabidopsis roots and shoots

ABSTRACT Characterizing the molecular mechanisms governing the response of plant roots and shoots to drought stress could aid the development of strategies aiming to ameliorate drought stress. Small open reading frames (sORFs), putatively encoding small peptides, may play a significant role in the response to different abiotic stresses. Microarray analyses revealed that after 5, 7 and 9 d of a drought treatment, 2, 77, and 104 sORFs were up-regulated in roots, respectively; while the number of upregulated sORFs in shoots was 12, 45, and 158, respectively. RT-qPCR analysis confirmed the up-regulated expression of ATRIKEN29196 and ATRIKEN32280 specifically in roots. The identified upregulated sORFs, particularly those in roots, may contribute to drought stress tolerance.
The Role of Attention in a Joint-Action Effect

The most common explanation for joint-action effects has been the action co-representation account in which observation of another's action is represented within one's own action system. However, recent evidence has shown that the most prominent of these joint-action effects (i.e., the Social Simon effect), can occur when no co-actor is present. In the current work we examined whether another joint-action phenomenon (a movement congruency effect) can be induced when a participant performs their part of the task with a different effector to that of their co-actor and when a co-actor's action is replaced by an attention-capturing luminance signal. Contrary to what is predicted by the action co-representation account, results show that the basic movement congruency effect occurred in both situations. These findings challenge the action co-representation account of this particular effect and suggest instead that it is driven by bottom-up mechanisms.
The Association Between Depressive Symptoms and Cognitive Functioning in Older Hispanic/Latino Adults Enrolled in an Exercise Intervention: Results From the “¡Caminemos!” Study

Objective: We examined the association between depressive symptoms and cognitive functioning in older Hispanics/Latinos enrolled in an exercise intervention. Method: We analyzed baseline, 1-year, and 2-year in-person interview data collected from Hispanics/Latinos aged ≥60 years participating in an exercise intervention across 27 senior centers (N = 572). Results: Mean age was 73.13 years; 77% female. At baseline, older adults screening positive for depression were 1.58 times more likely to experience cognitive impairment (p = .04); controlling for demographics and comorbid chronic conditions. Compared to peers with little to no depressive symptoms, lower cognitive functioning scores were evident at each follow-up assessment point where elevated depressive symptoms were present, but baseline depression was not associated with cognitive function in longitudinal analyses. Discussion: In older Hispanics/Latinos enrolled in an exercise intervention, though baseline depression did not predict cognitive function over time, elevated symptoms of depression were associated with greater cognitive impairment at every point in this study.
Merkel cell polyomavirus and Merkel cell carcinoma

Merkel cell polyomavirus (MCPyV) causes the highly aggressive and relatively rare skin cancer known as Merkel cell carcinoma (MCC). MCPyV also causes a lifelong yet relatively innocuous infection and is one of 14 distinct human polyomaviruses species. Although polyomaviruses typically do not cause illness in healthy individuals, several can cause catastrophic diseases in immunocompromised hosts. MCPyV is the only polyomavirus clearly associated with human cancer. How MCPyV causes MCC and what oncogenic events must transpire to enable this virus to cause MCC is the focus of this essay. This article is part of the themed issue ‘Human oncogenic viruses’.
Periprocedural myocardial infarction and injury in elective coronary stenting

Aims To assess the incidence, risk factors and prognosis of periprocedural myocardial infarction (MI) and myocardial injury in patients undergoing elective percutaneous coronary intervention (PCI). Methods and results We included all consecutive patients who underwent elective PCI with a negative troponin level at admission from 1 January 2014 to 31 December 2015. The primary endpoint was defined as the composite of periprocedural MI (Type 4a MI), stent thrombosis (Type 4b MI), and myocardial injury according to the Third universal definition of MI. Multivariable analysis was performed to identify independent predictors of periprocedural MI and myocardial injury and its relation to 30-day and 1-year clinical outcome. Of the 1390 elective PCI patients, the primary endpoint occurred in 28.7% of patients, including 7.0% of Type 4a MI, 0.14% of Type 4b MI, and 21.6% of myocardial injury. Independent risk factors for the occurrence of the primary endpoint were left main PCI, total stent length >30 mm, multiple stenting, chronic kidney disease (estimated glomerular filtration rate <60 mL/min) and age >75 years. At 30 days, patients with periprocedural MI and myocardial injury had a higher rate of cardiovascular events [5.5% vs. 1.2%, adjusted hazard ratio (adjHR) = 3.8, 95% confidence interval (CI) 1.9-6.9; P < 0.001] mainly driven by ischaemic events (3.2% vs. 0.6%, HR 5.9, 95% CI 2.9-20; P < 0.0001). At 1-year, the risk of ischemic events remained higher in the periprocedural MI and myocardial injury group (adjHR = 1.7, 95% CI 1.1-2.6; P = 0.004). Conclusions Periprocedural MI and injury are frequent complications of elective PCI associated with an increased rate of cardiovascular events at 30 days and 1 year.