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The Transition Online: A Mixed-Methods Study of the Impact of COVID-19 on Students with Disabilities in Higher EducationFollowing the World Health Organization’s announcement of the global pandemic because of the Coronavirus Disease 2019, most Canadian universities transitioned to offering their courses exclusively online. One group affected by this transition was students with disabilities. Previous research has shown that the university experience for students with disabilities differs from those of their non-disabled peers. However, their unique needs are often not taken into consideration. As a result, students can become marginalized and alienated from the online classroom. In partnership with Student Accessibility Services, this research revealed the impact of the transition to online learning because of the pandemic for university students with disabilities. Students registered with Student Accessibility Services completed a survey about the effects of online learning during a pandemic on the students’ lives, education, and instructional and accommodation. It was clear from the results that online education during COVID-19 affected all aspects of the students’ lives, particularly to their mental health. This research provided a much-needed opportunity for students with disabilities to share the factors influencing their educational experience and identified recommendations instructors should consider when developing online courses to increase accessibility and improve engagement.
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The role of the arousal system in age‐related differences in cortical functional network architectureA common finding in the aging literature is that of the brain's decreased within- and increased between-network functional connectivity. However, it remains unclear what is causing this shift in network organization with age. Given the essential role of the ascending arousal system (ARAS) in cortical activation and previous findings of disrupted ARAS functioning with age, it is possible that age differences in ARAS func- tioning contribute to disrupted cortical connectivity. We test this possibility here using resting state fMRI data from over 500 individuals across the lifespan from the Cambridge Center for Aging and Neuroscience (Cam-CAN) population-based cohort. Our results show that ARAS-cortical connectivity declines with age and, consistent with our expectations, significantly mediates some age-related differences in connec- tivity within and between association networks (specifically, within the default mode and between the default mode and salience networks). Additionally, connectivity between the ARAS and association networks predicted cognitive performance across several tasks over and above the effects of age and connectivity within the cortical networks themselves. These findings suggest that age differences in cortical connec- tivity may be driven, at least in part, by altered arousal signals from the brainstem and that ARAS–cortical connectivity relates to cognitive performance with age.
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Current Evidence of the Role of the Myokine Irisin in CancerRegular exercise/physical activity is beneficial for the health of an individual and lowers the risk of getting different diseases, including cancer. How exactly exercise results in these health benefits is not known. Recent studies suggest that the molecule irisin released by muscles into the blood stream after exercise may be responsible for these effects. This review summarizes all the available in vitro/cell culture, animal and human studies that have investigated the relationship between cancer and irisin with the aim to shed light and understand the possible role of irisin in cancer. The majority of the in vitro studies indicate anticancer properties of irisin, but more animal and human studies are required to better understand the exact role of irisin in cancer.
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Domains of spirituality and their importance to the health of 75 533 adolescents in 12 countriesSpirituality is considered by many to be an important domain of health. It is sometimes measured in four domains of connections: to oneself, to others, to nature and to the transcendent. While the importance of such connections is recognized as a fundamental human right for children, few interna- tional studies have studied their impacts on the health and well-being of young people. In this study of young people conducted over 4 years in 12 countries, we examined the perceived importance of each of four spiritual health domains and how they each related to positive mental health status in >75 000 adolescents. ‘Connections to self’ were consistently viewed as most important among boys and girls in all 12 countries. Fostering of strong connections to self, which involves cultivating a sense of meaning, purpose and joy in the lives of adolescents, appears most fundamental to achieving men- tal health and well-being. This may be achieved directly through a focus on connections to self, or in- directly by focusing on the indirect effects of the other three domains on mental health. This opens up many opportunities for health promotion in child populations, internationally.
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Family as a health promotion setting: A scoping review of conceptual models of the health-promoting familyBackground The family is a key setting for health promotion. Contemporary health promoting family models can establish scaffolds for shaping health behaviors and can be useful tools for education and health promotion. Objectives The objective of this scoping review is to provide details as to how conceptual and theoretical models of the health promoting potential of the family are being used in health promotion contexts. Design Guided by PRISMA ScR guidelines, we used a three-step search strategy to find relevant papers. This included key-word searching electronic databases (Medline, PSycINFO, Embase, and CINAHL), searching the reference lists of included studies, and intentionally searching for grey literature (in textbooks, dissertations, thesis manuscripts and reports.) Results After applying inclusion and exclusion criteria, the overall search generated 113 included manuscripts/chapters with 118 unique models. Through our analysis of these models, three main themes were apparent: 1) ecological factors are central components to most models or conceptual frameworks; 2) models were attentive to cultural and other diversities, allowing room for a wide range of differences across family types, and for different and ever-expanding social norms and roles; and 3) the role of the child as a passive recipient of their health journey rather than as an active agent in promoting their own family health was highlighted as an important gap in many of the identified models. Conclusions This review contributes a synthesis of contemporary literature in this area and supports the priority of ecological frameworks and diversity of family contexts. It encourages researchers, practitioners and family stakeholders to recognize the value of the child as an active agent in shaping the health promoting potential of their family context.
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Abscisic acid implicated in differential plant responses of Phaseolus vulgaris during endophytic colonization by Metarhizium and pathogenic colonization by FusariumMetarhizium robertsii is an insect pathogen as well as an endophyte, and can antagonize the phytopathogen, Fusarium solani during bean colonization. However, plant immune responses to endophytic colonization by Metarhizium are largely unknown. We applied comprehensive plant hormone analysis, transcriptional expression and stomatal size analysis in order to examine plant immune responses to colonization by Metarhizium and/or Fusarium. The total amount of abscisic acid (ABA) and ABA metabolites decreased significantly in bean leaves by plant roots colonized by M. robertsii and increased significantly with F. solani compared to the un-inoculated control bean plant. Concomitantly, in comparison to the un-inoculated bean, root colonization by Metarhizium resulted in increased stomatal size in leaves and reduced stomatal size with Fusarium. Meanwhile, expression of plant immunity genes was repressed by Metarhizium and, alternately, triggered by Fusarium compared to the un-inoculated plant. Furthermore, exogenous application of ABA resulted in reduction of bean root colonization by Metarhizium but increased colonization by Fusarium compared to the control without ABA application. Our study suggested that ABA plays a central role in differential responses to endophytic colonization by Metarhizium and pathogenic colonization by Fusarium and, we also observed concomitant differences in stomatal size and expression of plant immunity genes.
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Do weight perception and bullying victimization account for links between weight status and mental health among adolescents?Background: The purpose of this study was to explore whether the way youth perceive their weight and their experiences of bullying victimization account for the increased risk of depression and anxiety symptoms, and poor psychosocial well-being, associated with overweight/obesity in a large sample of Canadian secondary school students. We also explored if associations differed by gender. Methods: We used cross-sectional survey data from year 7 (2018–19) of the COMPASS study. The sample included 57,059 students in grades 9–12 (Secondary III-V in Quebec) at 134 Canadian secondary schools (Alberta, British Columbia, Ontario, Quebec). First, multiple regression models tested associations between body mass index (BMI) classification and mental health outcomes (anxiety [GAD-7] and depression [CESD-10] symptoms, and psychosocial well-being [Diener’s Flourishing Scale]). Second, weight perception and bullying victimization were added to the models. Models were stratified by gender and controlled for sociodemographic covariates and school clustering. Results: When weight perception and bullying victimization were added to the models, obesity BMI status no longer predicted internalizing symptoms and flourishing scores relative to normal-weight BMIs. Students with ‘overweight’ or ‘underweight’ perceptions, and experiences of bullying victimization in the past month, reported higher anxiety and depressive symptomatology, and lower flourishing levels, in comparison to students with ‘about right’ weight perceptions and without experiences of bullying victimization, respectively, controlling for BMI status. Results were largely consistent across boys and girls. Conclusions: Results suggest perceptions of weight and experiences of bullying independently contribute to differences in mental health outcomes by weight status among youth. Continued efforts targeting weight-based bullying and weight bias, and the promotion of body size acceptance and positive body image, may help reduce the risk of mental illness and poor mental health among adolescents.
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Individual Differences in Attentional Breadth Changes Over Time: An Event-Related Potential InvestigationEvent-related potentials (ERPs) to hierarchical stimuli have been compared for global/ local target trials, but the pattern of results across studies is mixed with respect to understanding how ERPs differ with local and global bias. There are reliable interindividual differences in attentional breadth biases. This study addresses two questions. Can these interindividual differences in attentional breadth be predicted by interindividual ERP differences to hierarchical stimuli? Can attentional breadth changes over time within participants (i.e., intraindividual differences) be predicted by ERPs changes over time when viewing hierarchical stimuli? Here, we estimated attentional breadth and isolated ERPs in response to Navon letter stimuli presented at two time points. We found that interindividual differences in ERPs at Time 1 did not predict attentional breadth differences across individuals at Time 1. However, individual differences in changes to P1, N1, and P3 ERPs to hierarchical stimuli from Time 1 to Time 2 were associated with individual differences in changes in attentional breadth from Time 1 to Time 2. These results suggest that attentional breadth changes within individuals over time are reflected in changes in ERP responses to hierarchical stimuli such that smaller N1s and larger P3s accompany a shift to processing the newly prioritized level, suggesting that the preferred level required less perceptual processing and elicited more attention.
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Non-HDL cholesterol level and depression among Canadian elderly—a cross-sectional analysis of the baseline data from the CLSATo explore whether nonhigh-density-lipoprotein cholesterol (non-HDL-c) is associated with depression, a total of 26 819 Canadians aged 45–85 from the Canadian Longitudinal Study on Aging (CLSA) were included in analysis. Non-HDL-c, the difference between total-c and HDL-c, was categorized into five levels, i.e., <2.6, 2.6 to <3.7, 3.7 to <4.8, 4.8 to 5.7, and ≥5.7 mmol/L. History of clinical depression was collected by questionnaire at an in-home interview, and current potential depression status was determined by CES-D10 (Center for Epidemiological Studies Depression Scale 10 questions version) score, i.e., ≥10 vs. <10. Logistic continuation ratio model for ordinal data was used to estimate the odds of being at or above a higher non-HDL-c category for depression status. Compared with those without clinical depression history and currently undepressed, the adjusted odds ratios (95% CI) were 1.09 (1.02, 1.17) for those without clinical depression history but currently depressed, 1.05 (0.98, 1.12) for those had clinical depression history but currently undepressed, and 1.21 (1.10, 1.32) for those had clinical depression history and currently depressed. The average of non-HDL-c for four depression groups were 3.64, 3.71, 3.69, and 3.82 mmol/L, respectively, and group 4 was statistically higher than others (p < 0.001). In conclu- sion, people with both current depression and a history clinical depression are at an increased risk of having high level of non-HDL-c.
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The Endocannabinoid System and Invertebrate Neurodevelopment and RegenerationCannabis has long been used for its medicinal and psychoactive properties. With the rela- tively new adoption of formal medicinal cannabis regulations worldwide, the study of cannabinoids, both endogenous and exogenous, has similarly flourished in more recent decades. In particular, research investigating the role of cannabinoids in regeneration and neurodevelopment has yielded promising results in vertebrate models. However, regeneration-competent vertebrates are few, whereas a myriad of invertebrate species have been established as superb models for regeneration. As such, this review aims to provide a comprehensive summary of the endocannabinoid system, with a focus on current advances in the area of endocannabinoid system contributions to invertebrate neurodevelopment and regeneration.
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Deciphering mollusc shell production: the roles of genetic mechanisms through to ecology, aquaculture and biomimeticsMost molluscs possess shells, constructed from a vast array of microstructures and architectures. The fully formed shell is composed of calcite or aragonite. These CaCO3 crystals form complex biocomposites with proteins, which although typ- ically less than 5% of total shell mass, play significant roles in determining shell microstructure. Despite much research effort, large knowledge gaps remain in how molluscs construct and maintain their shells, and how they produce such a great diversity of forms. Here we synthesize results on how shell shape, microstructure, composition and organic content vary among, and within, species in response to numerous biotic and abiotic factors. At the local level, temperature, food supply and predation cues significantly affect shell morphology, whilst salinity has a much stronger influence across lat- itudes. Moreover, we emphasize how advances in genomic technologies [e.g. restriction site-associated DNA sequencing (RAD-Seq) and epigenetics] allow detailed examinations of whether morphological changes result from phenotypic plas- ticity or genetic adaptation, or a combination of these. RAD-Seq has already identified single nucleotide polymorphisms associated with temperature and aquaculture practices, whilst epigenetic processes have been shown significantly to mod- ify shell construction to local conditions in, for example, Antarctica and New Zealand. We also synthesize results on the costs of shell construction and explore how these affect energetic trade-offs in animal metabolism. The cellular costs are still debated, with CaCO3 precipitation estimates ranging from 1–2 J/mg to 17–55 J/mg depending on experimental and environmental conditions. However, organic components are more expensive ($29 J/mg) and recent data indicate transmembrane calcium ion transporters can involve considerable costs. This review emphasizes the role that molecular analyses have played in demonstrating multiple evolutionary origins of biomineralization genes. Although these are char- acterized by lineage-specific proteins and unique combinations of co-opted genes, a small set of protein domains have been identified as a conserved biomineralization tool box. We further highlight the use of sequence data sets in providing candidate genes for in situ localization and protein function studies. The former has elucidated gene expression modular- ity in mantle tissue, improving understanding of the diversity of shell morphology synthesis. RNA interference (RNAi) and clustered regularly interspersed short palindromic repeats - CRISPR-associated protein 9 (CRISPR-Cas9) experi- ments have provided proof of concept for use in the functional investigation of mollusc gene sequences, showing for example that Pif (aragonite-binding) protein plays a significant role in structured nacre crystal growth and that the Lsdia1 gene sets shell chirality in Lymnaea stagnalis. Much research has focused on the impacts of ocean acidification on molluscs. Initial studies were predominantly pessimistic for future molluscan biodiversity. However, more sophisticated experi- ments incorporating selective breeding and multiple generations are identifying subtle effects and that variability within mollusc genomes has potential for adaption to future conditions. Furthermore, we highlight recent historical studies based on museum collections that demonstrate a greater resilience of molluscs to climate change compared with exper- imental data. The future of mollusc research lies not solely with ecological investigations into biodiversity, and this review synthesizes knowledge across disciplines to understand biomineralization. It spans research ranging from evolution and development, through predictions of biodiversity prospects and future-proofing of aquaculture to identifying new biomi- metic opportunities and societal benefits from recycling shell products.
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Azo synthesis meets molecular iodine catalysisA metal-free synthetic protocol for azo compound formation by the direct oxidation of hydrazine HN–NH bonds to azo group functionality catalyzed by molecular iodine is disclosed. The strengths of this reactivity include rapid reaction times, low catalyst loadings, use of ambient dioxygen as a stoichiometric oxidant, and ease of experimental set-up and azo product isolation. Mechanistic studies and density functional theory computations offering insight into this reactivity, as well as the events leading to azo group formation are presented. Collectively, this study expands the potential of main-group element iodine as an inexpensive catalyst, while delivering a useful transformation for forming azo compounds.
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First evidence of the mutations associated with pyrethroid resistance in head lice (Phthiraptera: Pediculidae) from HondurasThe human head louse, Pediculus humanus capitis, is a cosmopolitan blood-sucking ectoparasite affecting mostly schoolchildren in both developed and developing countries. In Honduras, chemical pediculicides are the first line of treatment, with permethrin as their main active ingredient. Despite the extended use of these products, there is currently no research investigating insecticide resistance in Honduran head lice. In head lice, the most common mechanism is knockdown resistance (kdr), which is the result of two point mutations and the associated amino acid substitutions, T917I and L920F, within the voltage-sensitive sodium channel (VSSC). METHODSGenomic DNA was extracted from 83 head lice collected in the localities of San Buenaventura and La Hicaca, Honduras. Polymerase chain reaction (PCR) was used to amplify a 332-bp fragment of the VSSC gene that contains a site affected by C/T mutation which results in a T917I amino acid substitution on each human head louse genomic DNA fragments. RESULTSThe C/T non-synonymous mutation which results in the T917I kdr amino acid substitution was detected in both head lice populations at frequencies ranging between 0.45-0.5. Globally, the frequency of this substitution was 0.47. Of these, 5 (6.1%) were homozygous susceptible and 78 (93.9%) were heterozygotes. The kdr-resistant homozygote (RR) was not detected in the studied populations. Thus, 93.9% of the head lice collected in Honduras harbored only one T917I allele. Exact test for the Hardy-Weinberg equilibrium for both localities showed that genotype frequencies differed significantly from expectation. In addition, San Buenaventura and La Hicaca populations had an inbreeding coefficient (Fis) < 0, suggesting an excess of heterozygotes. CONCLUSIONSTo our knowledge, this is the first study showing the presence of the C/T mutation responsible of the T917I kdr allele associated with pyrethroid resistance in P. h. capitis from Honduras. The PCR-restriction fragment length polymorphism (RFLP) employed here has demonstrated to be a reliable, economic, and reproducible assay that can be used to accurately genotype individual head lice for the mutation encoding the resistance-conferring T917I amino acid substitution. This highlights the necessity of proactive resistance management programmes designed to detect pyrethroid mutations before they become established within populations of head lice.
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Anticancer Properties of Carnosol: A Summary of In Vitro and In Vivo EvidenceCancer is characterized by unrestricted cell proliferation, inhibition of apoptosis, enhanced invasion and migration, and deregulation of signalling cascades. These properties lead to uncontrolled growth, enhanced survival, and the formation of tumours. Carnosol, a naturally occurring phyto-polyphenol (diterpene) found in rosemary, has been studied for its extensive antioxidant, anti-inflammatory, and anticancer effects. In cancer cells, carnosol has been demonstrated to inhibit cell proliferation and survival, reduce migration and invasion, and significantly enhance apoptosis. These anticancer effects of carnosol are mediated by the inhibition of several signalling molecules including extracellular signal-regulated kinase (ERK), p38, c-Jun N-terminal kinase (JNK), Akt, mechanistic target of rapamycin (mTOR) and cyclooxygenase-2 (COX-2). Additionally, carnosol prevents the nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and promotes apoptosis, as indicated by increased levels of cleaved caspase-3, -8, -9, increased levels of the pro-apoptotic marker Bcl-2-associated X (BAX), and reduced levels of the anti-apoptotic marker B-cell lymphoma 2 (Bcl-2). The current review summarizes the existing in vitro and in vivo evidence examining the anticancer effects of carnosol across various tissues.
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On Whether Task Experience of the Peer Differentially Impacts Feedback Scheduling and Skill Acquisition of a LearnerPrevious research has shown that peers without task experience provided knowledge of results (KR) as effectively as performers who self-controlled their own KR schedule ( McRae et al., 2015 ). In the present experiment, a group of participants first practiced a motor task while self-controlling their KR during a defined acquisition period. Twenty-four hours after their last retention trial, these participants with motor experience then provided KR to a learner during their skill acquisition. Participants were required to learn a serial-timing task with a goal of 2,500 ms. Participants completed a defined acquisition period and then returned 24 h later for a retention test. In retention, learners who received KR from experienced peers were predicted to outperform learners who received KR from inexperienced peers. The results showed that performers learned the task similarly, independent of the peer’s previous task experience. However, the peer groups differed in their frequency of providing KR to the learner and showed a discrepancy between their self-reported KR provision strategy and when they actually provided KR. The results have theoretical implications for understanding the impact of self-control in motor learning contexts.
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Electrophysiological correlates of top-down attentional modulation in olfactionThe capacity to pay attention is important for the cognitive ability, for example, evaluating an object for its qualities. Attention can selectively prioritize the neural processes that are relevant to a given task. Neuroimaging investigations on human attention are primarily focused on vision to the exclusion of other sensory systems, particularly olfaction. Neural underpinnings of human olfactory attention are still not clearly understood. Here, we combined electroencephalographic measurements of olfactory event related potential with electrical neuroimaging to investigate how the neural responses after inhaling the same odor differ between conditions with varying levels of attention, and, in which brain areas. We examined the neural responses when participants attended to a rose-like odor of phenylethyl alcohol for evaluating its pleasantness versus its passive inhalation. Our results gathered significant evidence for attentional modulation of the olfactory neural response. The most prominent effect was found for the late positive component, P3, of olfactory event related potential within a second from the odor onset. The source reconstruction of this data revealed activations in a distributed network of brain regions predominantly in inferior frontal cortex, insula, and inferior temporal gyrus. These results suggest that the neuronal modulations from attention to olfactory pleasantness may be subserved by this network.
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Calmodulin-Binding Proteins in Muscle: A Minireview on Nuclear Receptor Interacting Protein, Neurogranin, and Growth-Associated Protein 43Calmodulin (CaM) is an important Ca2+-sensing protein with numerous downstream targets that are either CaM-dependant or CaM-regulated. In muscle, CaM-dependent proteins, which are critical regulators of dynamic Ca2+ handling and contractility, include calcineurin (CaN), CaM-dependant kinase II (CaMKII), ryanodine receptor (RyR), and dihydropyridine receptor (DHPR).CaM-regulated targets include genes associated with oxidative metabolism, muscle plasticity, and repair. Despite its importance in muscle, the regulation of CaM—particularly its availability to bind to and activate downstream targets—is an emerging area of research. In this minireview, we discuss recent studies revealing the importance of small IQ motif proteins that bind to CaM to either facilitate (nuclear receptor interacting protein; NRIP) its activation of downstream targets, or sequester (neurogranin, Ng; and growth-associated protein 43, GAP43) CaM away from their downstream targets. Specifically, we discuss recent studies that have begun uncovering the physiological roles of NRIP, Ng, and GAP43 in skeletal and cardiac muscle, thereby highlighting the importance of endogenously expressed CaM-binding proteins and their regulation of CaM in muscle.
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High Endemicity of Soil-Transmitted Helminths in a Population Frequently Exposed to Albendazole but No Evidence of Antiparasitic ResistanceSoil-transmitted helminths (STHs) are gastrointestinal parasites widely distributed in tropical and subtropical areas. Mass drug administration (MDA) of benzimidazoles (BZ) is the most recommended for STH control. These drugs have demonstrated limited efficacy against Trichuris trichiura and the long-term use of single-dose BZ has raised concerns of the possible emergence of genetic resistance. The objective of this investigation was to determine whether genetic mutations associated with BZ resistance were present in STH species circulating in an endemic region of Honduras. Methods: A parasitological survey was performed as part of this study, the Kato–Katz technique was used to determine STH prevalence in children of La Hicaca, Honduras. A subgroup of children received anthelminthic treatment in order to recover adult parasite specimens that were analyzed through molecular biology techniques. Genetic regions containing codons 200, 198, and 167 of the β-tubulin gene of Ascaris lumbricoides and Trichuris trichiura were amplified and sequenced. Results: Stool samples were collected from 106 children. The overall STH prevalence was 75.47%, whereby T. trichiura was the most prevalent helminth (56.6%), followed by A. lumbricoides (17%), and hookworms (1.9%). Eighty-five sequences were generated for adjacent regions to codons 167, 198, and 200 of the β-tubulin gene of T. trichiura and A. lumbricoides specimens. The three codons of interest were found to be monomorphic in all the specimens. Conclusion: Although the inability to find single-nucleotide polymorphisms (SNPs) in the small sample analyzed for the present report does not exclude the possibility of their occurrence, these results suggest that, at present, Honduras’s challenges in STH control may not be related to drug resistance but to environmental conditions and/or host factors permitting reinfections.
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Metarhizium robertsii ammonium permeases (MepC and Mep2) contribute to rhizoplane colonization and modulates the transfer of insect derived nitrogen to plantsThe endophytic insect pathogenic fungi (EIPF) Metarhizium promotes plant growth through symbiotic association and the transfer of insect-derived nitrogen. However, little is known about the genes involved in this association and the transfer of nitrogen. In this study, we assessed the involvement of six Metarhizium robertsii genes in endophytic, rhizoplane and rhizospheric colonization with barley roots. Two ammonium permeases (MepC and Mep2) and a urease, were selected since homologous genes in arbuscular mycorrhizal fungi were reported to play a pivotal role in nitrogen mobilization during plant root colonization. Three other genes were selected on the basis on RNA-Seq data that showed high expression levels on bean roots, and these encoded a hydrophobin (Hyd3), a subtilisin-like serine protease (Pr1A) and a hypothetical protein. The root colonization assays revealed that the deletion of urease, hydrophobin, subtilisin-like serine protease and hypothetical protein genes had no impact on endophytic, rhizoplane and rhizospheric colonization at 10 or 20 days. However, the deletion of MepC resulted in significantly increased rhizoplane colonization at 10 days whereas ΔMep2 showed increased rhizoplane colonization at 20 days. In addition, the nitrogen transporter mutants also showed significantly higher 15N incorporation of insect derived nitrogen in barley leaves in the presence of nutrients. Insect pathogenesis assay revealed that disruption of MepC, Mep2, urease did not reduce virulence toward insects. The enhanced rhizoplane colonization of ΔMep2 and ΔMepC and insect derived nitrogen transfer to plant hosts suggests the role of MepC and Mep2 in Metarhizium-plant symbiosis.
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A Low-Therapeutic Dose of Lithium Inhibits GSK3 and Enhances Myoblast Fusion in C2C12 CellsGlycogen synthase kinase 3 (GSK3) slows myogenic differentiation and myoblast fusion partly by inhibiting the Wnt/β-catenin signaling pathway. Lithium, a common medication for bipolar disorder, inhibits GSK3 via Mg+ competition and increased Ser21 (GSK3α) or Ser9 (GSK3β) phosphorylation, leading to enhanced myoblast fusion and myogenic differentiation. However, previous studies demonstrating the effect of lithium on GSK3 have used concentrations up to 10 mM, which greatly exceeds concentrations measured in the serum of patients being treated for bipolar disorder (0.5–1.2 mM). Here, we determined whether a low-therapeutic (0.5 mM) dose of lithium could promote myoblast fusion and myogenic differentiation in C2C12 cells. C2C12 myotubes differentiated for three days in media containing 0.5 mM lithium chloride (LiCl) had significantly higher GSK3β (ser9) and GSK3α (ser21) phosphorylation compared with control myotubes differentiated in the same media without LiCl (+2–2.5 fold, p < 0.05), a result associated with an increase in total β-catenin. To further demonstrate that 0.5 mM LiCl inhibited GSK3 activity, we also developed a novel GSK3-specific activity assay. Using this enzyme-linked spectrophotometric assay, we showed that 0.5 mM LiCl-treated myotubes had significantly reduced GSK3 activity (−86%, p < 0.001). Correspondingly, 0.5 mM LiCl treated myotubes had a higher myoblast fusion index compared with control (p < 0.001) and significantly higher levels of markers of myogenesis (myogenin, +3-fold, p < 0.001) and myogenic differentiation (myosin heavy chain, +10-fold, p < 0.001). These results indicate that a low-therapeutic dose of LiCl is sufficient to promote myoblast fusion and myogenic differentiation in muscle cells, which has implications for the treatment of several myopathic conditions
