Miracle-dz/UniFAR-FTUs huggingface dataset:
Reactive Astrogliosis in an Experimental Model of Fibromyalgia: Effect of Dexmedetomidine

To our knowledge, this is the first study which investigates the induction of neuroinflammation in rats using an acidic-saline model of fibromyalgia. It is well known that the hippocampus has a fundamental role in pain perception, and astrocytes play a crucial role in pain signaling. Our aim is to evaluate the ability of dexmedetomidine to attenuate the inflammatory responses induced in astrocytes. In a group of healthy rats, induction of chronic muscle pain by intramuscular injection of 100 µL of acidic saline on days 0 and 5 resulted in peripheral sensitization (measured using the von Frey test) and significant (p < 0.05) increases in IL-1β (160.2 ± 1.1 to 335.2 ± 1.8), IL-6 (100.1 ± 1.4 to 202.4 ± 1.1), and TNF-α (60.0 ± 0.7 to 115.5 ± 1). Light and electron microscopy revealed degenerative changes in the hippocampus and reactive astrogliosis. Immunohistochemistry showed increased expression of glial fibrillary acid protein and inducible nitric oxide synthase. Surprisingly, treatment with a single dose of an α2-adrenergic agonist, dexmedetomidine (5 µg/kg i.p.), attenuated these changes. This trial suggests that dexmedetomidine possibly directly acts on astrocytes, and a peripheral action is also suggested.
The Effect of Glyphosate on Human Sperm Motility and Sperm DNA Fragmentation

Glyphosate is the active ingredient of Roundup®, which is one of the most popular herbicides worldwide. Although many studies have focused on the reproductive toxicity of glyphosate or glyphosate-based herbicides, the majority of them have concluded that the effect of the specific herbicide is negligible, while only a few studies indicate the male reproductive toxicity of glyphosate alone. The aim of the present study was to investigate the effect of 0.36 mg/L glyphosate on sperm motility and sperm DNA fragmentation (SDF). Thirty healthy men volunteered to undergo semen analysis for the purpose of the study. Sperm motility was calculated according to WHO 2010 guidelines at collection time (zero time) and 1 h post-treatment with glyphosate. Sperm DNA fragmentation was evaluated with Halosperm® G2 kit for both the control and glyphosate-treated sperm samples. Sperm progressive motility of glyphosate-treated samples was significantly reduced after 1 h post-treatment in comparison to the respective controls, in contrast to the SDF of glyphosate-treated samples, which was comparable to the respective controls. Conclusively, under these in vitro conditions, at high concentrations that greatly exceed environmental exposures, glyphosate exerts toxic effects on sperm progressive motility but not on sperm DNA integrity, meaning that the toxic effect is limited only to motility, at least in the first hour.
Advance Publication Experimental Animals

30 Mammalian postnatal growth is regulated primarily by the growth hormone (GH)/insulin-like growth 31 factor I (IGF-I) axis. MafB is a basic leucine zipper (bZip) transcription factor that has pleiotropic 32 functions. Although MafB plays a critical role in fetal brain development, such as in guidance for 33 hindbrain segmentation, its postnatal role in neurons remains to be elucidated. To investigate this, we 34 used neuron-specific Mafb conditional knockout (cKO) mice. In addition to an approximately 50% 35 neonatal viability, the Mafb cKO mice exhibited growth retardation without apparent signs of low 36 energy intake. Notably, serum IGF-I levels of these mice in the postnatal stage were lower than those 37 of control mice. They seemed to have a neuroendocrine dysregulation, as shown by the upregulation 38 of serum GH levels in the resting state and an inconsistent secretory response of GH upon 39 administration of growth hormone-releasing hormone. These findings reveal that neuronal MafB 40 plays an important role in postnatal development regulated by the GH/IGF-I axis. (157 words) 41 Nes-Cre;R26GRR deletion of
High-performance reoxygenation from PLGA-PEG/PFOB emulsions: a feedback relationship between ROS and HIF-1α

Background Hypoxemia is one of the most common pathological processes in various clinical diseases. Methods A novel emulsion of poly(lactide-co-glycolide)-poly(ethylene glycol)/perfluorooctyl bromide has been developed to improve arterial hypoxemia through pulmonary drug delivery. Hypoxia-reoxygenation experiment was used to investigate the ability of the emulsion to supply oxygen and the saline lavage acute lung injury model was established to evaluate oxygen supply of the emulsion. Results It has been demonstrated that an apparent increase has been detected in the cytotoxicity test of the emulsion, indicating its lower cell toxicity. A hypoxia-reoxygenation experiment uncovered the fact that notable cell growth was observed after reoxygenation with poly(lactide-co-glycolide)-poly(ethylene glycol)/perfluorooctyl bromide emulsion because of the ability of the emulsion to supply oxygen adequately and reasonably. Moreover, the level of intracellular reactive oxygen species was significantly enhanced during hypoxia, which further influenced the concentration and activity of hypoxia-inducible factor-1α (HIF-1α). Furthermore, the upregulated expression of HIF-1α during hypoxia has verified that certain emulsions can increase HIF-1α content and relieve hypoxia, which further indicates HIF-1α plays an essential role in improving cell viability. Afterwards, the saline lavage acute lung injury model was established to evaluate oxygen supply of the emulsion and the result shows considerable improvement of lung ventilation of rabbits. Conclusion We recommend that the feedback relationship between reactive oxygen species and HIF-1 plays an essential role in improving cell viability. It is anticipated that the emulsion will be applied in the field of alleviating hypoxemia.
Improving Nursing Students' Learning Outcomes in Fundamentals of Nursing Course through Combination of Traditional and e-Learning Methods

Background: Fundamentals of nursing course are prerequisite to providing comprehensive nursing care. Despite development of technology on nursing education, effectiveness of using e-learning methods in fundamentals of nursing course is unclear in clinical skills laboratory for nursing students. The aim of this study was to compare the effect of blended learning (combining e-learning with traditional learning methods) with traditional learning alone on nursing students' scores. Materials and Methods: A two-group post-test experimental study was administered from February 2014 to February 2015. Two groups of nursing students who were taking the fundamentals of nursing course in Iran were compared. Sixty nursing students were selected as control group (just traditional learning methods) and experimental group (combining e-learning with traditional learning methods) for two consecutive semesters. Both groups participated in Objective Structured Clinical Examination (OSCE) and were evaluated in the same way using a prepared checklist and questionnaire of satisfaction. Statistical analysis was conducted through SPSS software version 16. Results: Findings of this study reflected that mean of midterm (t = 2.00, p = 0.04) and final score (t = 2.50, p = 0.01) of the intervention group (combining e-learning with traditional learning methods) were significantly higher than the control group (traditional learning methods). The satisfaction of male students in intervention group was higher than in females (t = 2.60, p = 0.01). Conclusions: Based on the findings, this study suggests that the use of combining traditional learning methods with e-learning methods such as applying educational website and interactive online resources for fundamentals of nursing course instruction can be an effective supplement for improving nursing students' clinical skills.
Associations of Body Mass Index, Motor Performance, and Perceived Athletic Competence with Physical Activity in Normal Weight and Overweight Children

Children who are overweight and obese display lower physical activity levels than normal weight peers. Measures of weight status, perceived motor competence, and motor skill performance have been identified as potential correlates explaining this discrepancy. 1881 children (955 males; 926 females; 9.9 years) were assessed as part of the Physical Health Activity Study Team project. The age, habitual physical activity participation (PAP), body mass index (BMI), socioeconomic status (SES), motor performance (MP), and perceived athletic competence (PAC) of each child included were assessed. Gender-specific linear regression analyses (main effects model) were conducted to identify the percent variance in PAP explained by the following variables: BMI, MP, and PAC. For males, 18.3% of the variance in PAP was explained by BMI, MP, and PAC. PAC explained 17% of the variance, while MP, BMI, and SES only accounted for 0.6%, 0.7%, and 0.5%, respectively. PAC explained 17.5% of PAP variance in females; MP explained 0.8%. BMI, SES, and chronological age were not significant correlates of PAP in girls. An established repertoire of motor skill performance has been seen as a vehicle to PAP in children; however, this study indicates that PAC should not be overlooked in intervention strategies to promote increased PAP.
Genome‐Wide Genetic Dissection of Supernumerary Spikelet and Related Traits in Common Wheat

Branched spike or supernumerary spikelet (SS) is a naturally occurring variant in wheat and holds great potential for increasing the number of grains per spike, and ultimately, increasing wheat yield. However, detailed knowledge of the molecular basis of spike branching in common wheat is lacking. In the present study, a recombinant inbred line (RIL) population derived from the cross of an SS accession and an elite non‐SS line was developed and evaluated over four to six environments for seven SS‐related traits to identify the genetic basis of SS in wheat. A framework linkage map was generated using 939 diversity arrays technology (DArT) markers. Composite interval mapping (CIM) identified a total of seven consistent quantitative trait loci (QTL) located on five chromosomes (2D, 5B, 6A, 6B, and 7B), suggesting a polygenic inheritance of SS. The phenotypic variation explained (PVE) by individual QTL ranged from 3.3 to 37.3%. The QTL located on 2D (QSS.ndsu‐2D) and 7B (QSS.ndsu‐7B.2) have major effects (PVE > 15%), while the remaining five QTL (QSS.ndsu‐5B, QSS.ndsu‐6A, QSS.ndsu‐6B.1, QSS.ndsu‐6B.2, QSS.ndsu‐7B.1) have minor effects (PVE < 15%). Comparison of the genomic locations of the QTL suggested that QSS.ndsu‐2D was located in the same regions on 2DS, where QTL for several traits have been reported. However, the remaining six QTL for SS are reported for the first time. Multiple interval mapping (MIM) showed that all seven QTL are involved in epistatic interaction. The major genomic regions controlling these SS‐related traits may prove invaluable for wheat improvement and could also be the target for future studies aimed at cloning these genes.
An Automated Sample Preparation Instrument to Accelerate Positive Blood Cultures Microbial Identification by MALDI-TOF Mass Spectrometry (Vitek®MS)

Sepsis is the leading cause of death among patients in intensive care units (ICUs) requiring an early diagnosis to introduce efficient therapeutic intervention. Rapid identification (ID) of a causative pathogen is key to guide directed antimicrobial selection and was recently shown to reduce hospitalization length in ICUs. Direct processing of positive blood cultures by MALDI-TOF MS technology is one of the several currently available tools used to generate rapid microbial ID. However, all recently published protocols are still manual and time consuming, requiring dedicated technician availability and specific strategies for batch processing. We present here a new prototype instrument for automated preparation of Vitek®MS slides directly from positive blood culture broth based on an “all-in-one” extraction strip. This bench top instrument was evaluated on 111 and 22 organisms processed using artificially inoculated blood culture bottles in the BacT/ALERT® 3D (SA/SN blood culture bottles) or the BacT/ALERT VirtuoTM system (FA/FN Plus bottles), respectively. Overall, this new preparation station provided reliable and accurate Vitek MS species-level identification of 87% (Gram-negative bacteria = 85%, Gram-positive bacteria = 88%, and yeast = 100%) when used with BacT/ALERT® 3D and of 84% (Gram-negative bacteria = 86%, Gram-positive bacteria = 86%, and yeast = 75%) with Virtuo® instruments, respectively. The prototype was then evaluated in a clinical microbiology laboratory on 102 clinical blood culture bottles and compared to routine laboratory ID procedures. Overall, the correlation of ID on monomicrobial bottles was 83% (Gram-negative bacteria = 89%, Gram-positive bacteria = 79%, and yeast = 78%), demonstrating roughly equivalent performance between manual and automatized extraction methods. This prototype instrument exhibited a high level of performance regardless of bottle type or BacT/ALERT system. Furthermore, blood culture workflow could potentially be improved by converting direct ID of positive blood cultures from a batch-based to real-time and “on-demand” process.
Speech Rate Entrainment in Children and Adults With and Without Autism Spectrum Disorder.

Purpose Conversational entrainment, a phenomenon whereby people modify their behaviors to match their communication partner, has been evidenced as critical to successful conversation. It is plausible that deficits in entrainment contribute to the conversational breakdowns and social difficulties exhibited by people with autism spectrum disorder (ASD). This study examined speech rate entrainment in children and adult populations with and without ASD. Method Sixty participants including typically developing children, children with ASD, typically developed adults, and adults with ASD participated in a quasi-conversational paradigm with a pseudoconfederate. The confederate's speech rate was digitally manipulated to create slow and fast speech rate conditions. Results Typically developed adults entrained their speech rate in the quasi-conversational paradigm, using a faster rate during the fast speech rate conditions and a slower rate during the slow speech rate conditions. This entrainment pattern was not evident in adults with ASD or in children populations. Conclusion Findings suggest that speech rate entrainment is a developmentally acquired skill and offers preliminary evidence of speech rate entrainment deficits in adults with ASD. Impairments in this area may contribute to the conversational breakdowns and social difficulties experienced by this population. Future work is needed to advance this area of inquiry.
Decision-making processes underlying pedestrian behaviours at signalised crossings: Part 2. Do pedestrians show cultural herding behaviour ?.

Followership is generally defined as a strategy that evolved to solve social coordination problems, and particularly those involved in group movement. Followership behaviour is particularly interesting in the context of road-crossing behaviour because it involves other principles such as risk-taking and evaluating the value of social information. This study sought to identify the cognitive mechanisms underlying decision-making by pedestrians who follow another person across the road at the green or at the red light in two different countries (France and Japan). We used agent-based modelling to simulate the road-crossing behaviours of pedestrians. This study showed that modelling is a reliable means to test different hypotheses and find the exact processes underlying decision-making when crossing the road. We found that two processes suffice to simulate pedestrian behaviours. Importantly, the study revealed differences between the two nationalities and between sexes in the decision to follow and cross at the green and at the red light. Japanese pedestrians are particularly attentive to the number of already departed pedestrians and the number of waiting pedestrians at the red light, whilst their French counterparts only consider the number of pedestrians that have already stepped off the kerb, thus showing the strong conformism of Japanese people. Finally, the simulations are revealed to be similar to observations, not only for the departure latencies but also for the number of crossing pedestrians and the rates of illegal crossings. The conclusion suggests new solutions for safety in transportation research.
Temperature-dependent toxicities of chlorothalonil and copper pyrithione to the marine copepod Tigriopus japonicus and dinoflagellate Pyrocystis lunula

The anticipated anthropogenically-driven climate change may ultimately result in increased incidents of temperature extremes that will have profound implications on the toxicity of chemical contaminants and hence their ecological risks to marine organisms in the tropics and subtropics. We hypothesised that chemical toxicity generally increases with increasing temperature over the thermal tolerance range (TTR) of a species, and is further exacerbated at extreme temperatures (i.e. lower or higher than the TTR). To test this hypothesis, we investigated the acute toxicity of two commonly used antifouling biocides, chlorothalonil and copper pyrithione (CuPT), to the marine copepod Tigriopus japonicus and dinoflagellate Pyrocystis lunula over a wide range of water temperatures. Our results verified that toxicities of the two biocides, in terms of 96-h LC50 (for T. japonicus) and 24-h EC50 (for P. lunula), were highly temperature-dependent, although the profile of temperature-dependency varied between the two chemicals. The LC50 values of T. japonicus exposed to CuPT decreased with increasing temperature between 15–31°C (i.e. assumed TTR), whereas the LC50 values at 4 and 35°C were significantly lower than those at 10 and 25°C, respectively. The toxicity of chlorothalonil to the copepod followed the same pattern of CuPT between 25 and 35°C but the LC50 values between 4 and 25°C were somehow indifferent. In P. lunula, a similar temperature-dependent toxicity was also observed for CuPT but not for chlorothalonil. Such dissimilar temperature-dependent toxicity profiles between the two biocides may be partially attributable to the differences in temperature-mediated modifications of their physicochemical properties, bioavailability, toxicokinetics, and thus resultant toxicity to the test organism.
Androgen receptor polyglutamine expansion drives age-dependent quality control defects and muscle dysfunction

Skeletal muscle has emerged as a critical, disease-relevant target tissue in spinal and bulbar muscular atrophy, a degenerative disorder of the neuromuscular system caused by a CAG/polyglutamine (polyQ) expansion in the androgen receptor (AR) gene. Here, we used RNA-sequencing (RNA-Seq) to identify pathways that are disrupted in diseased muscle using AR113Q knockin mice. This analysis unexpectedly identified substantially diminished expression of numerous ubiquitin/proteasome pathway genes in AR113Q muscle, encoding approximately 30% of proteasome subunits and 20% of E2 ubiquitin conjugases. These changes were age, hormone, and glutamine length dependent and arose due to a toxic gain of function conferred by the mutation. Moreover, altered gene expression was associated with decreased levels of the proteasome transcription factor NRF1 and its activator DDI2 and resulted in diminished proteasome activity. Ubiquitinated ADRM1 was detected in AR113Q muscle, indicating the occurrence of stalled proteasomes in mutant mice. Finally, diminished expression of Drosophila orthologues of NRF1 or ADRM1 promoted the accumulation of polyQ AR protein and increased toxicity. Collectively, these data indicate that AR113Q muscle develops progressive proteasome dysfunction that leads to the impairment of quality control and the accumulation of polyQ AR protein, key features that contribute to the age-dependent onset and progression of this disorder.
The Importance of Tyrosine Phosphorylation Control of Cellular Signaling Pathways in Respiratory Disease: pY and pY Not

&NA; Reversible phosphorylation of proteins on tyrosine residues is an essential signaling mechanism by which diverse cellular processes are closely regulated. The tight temporal and spatial control of the tyrosine phosphorylation status of proteins by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) is critical to cellular homeostasis as well as to adaptations to the external environment. Via regulation of cellular signaling cascades involving other protein kinases and phosphatases, receptors, adaptor proteins, and transcription factors, PTKs and PTPs closely control diverse cellular processes such as proliferation, differentiation, migration, inflammation, and maintenance of cellular barrier function. Given these key regulatory roles, it is not surprising that dysfunction of PTKs and PTPs is important in the pathogenesis of human disease, including many pulmonary diseases. The roles of various PTKs and PTPs in acute lung injury and repair, pulmonary fibrosis, pulmonary vascular disease, and inflammatory airway disease are discussed in this review. It is important to note that although there is overlap among many of these proteins in various disease states, the mechanisms by which they influence the pathogenesis of these conditions differ, suggesting wide‐ranging roles for these enzymes and their potential as therapeutic targets.
Nucleolar Localization of HIV-1 Rev Is Required, Yet Insufficient for Production of Infectious Viral Particles

Abstract Combination antiretroviral therapy fails in complete suppression of HIV-1 due to drug resistance and persistent latency. Novel therapeutic intervention requires knowledge of intracellular pathways responsible for viral replication, specifically those untargeted by antiretroviral drugs. An understudied phenomenon is the nucleolar localization of Rev phosphoprotein, which completes nucleocytoplasmic transport of unspliced/partially spliced HIV mRNA through multimerization with intronic cis-acting targets—the Rev-response element (RRE). Rev contains a nucleolar localization signal (NoLS) comprising the COOH terminus of the arginine-rich motif for accumulation within nucleoli—speculated as the interaction ground for Rev with cellular proteins mediating mRNA-independent nuclear export and splicing. Functionality of Rev nucleolar access during HIV-1 production and infection was investigated in the context of deletion and single-point mutations within Rev-NoLS. Mutations induced upon Rev-NoLS are hypothesized to inactivate the HIV-1 infectious cycle. HIV-1HXB2 replication ceased with Rev mutations lacking nucleolar access due to loss or replacement of multiple arginine residues. Rev mutations missing single arginine residues remained strictly nucleolar in pattern and participated in proviral production, however, with reduced efficiency. Viral RNA packaging also decreased in efficiency after expression of nucleolar-localizing mutations. These results were observed during propagation of variant HIV-1NL4-3 containing nucleolar-localizing mutations within the viral backbone (M4, M5, and M6). Lentiviral particles produced with Rev single-point mutations were transducible at extremely low frequency. Similarly, HIV-1NL4-3 Rev-NoLS variants lost infectivity, unlike virulent WT (wild type) HIV-1NL4-3. HIV-1NL4-3 variants were capable of CD4+ host entry and reverse transcription as WT HIV-1NL4-3, but lacked ability to complete a full infectious cycle. We currently reveal that viral integration is deregulated in the presence of Rev-NoLS mutations.