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The article focuses on the growing concerns about the integrity of scientific research worldwide, particularly regarding the handling of errors and retractions in published papers. Retraction Watch provides a valuable service by promptly highlighting challenges to recent publications, covering topics such as self-plagiarism, data manipulation, and mismanaged research studies.

This review identifies some key concepts of muscle regeneration, viewed from perspectives of classical and modern research. Early insights noted the pattern and sequence of regeneration across species was similar, regardless of the type of injury, and differed from epimorphic limb regeneration. While potential benefits of exercise for tissue repair was debated, regeneration was not presumed to deliver functional restoration, especially after ischemia–reperfusion injury; muscle could develop fibrosis and ectopic bone and fat. Standard protocols and tools were identified as necessary for tracking injury and outcomes. Current concepts vastly extend early insights. Myogenic regeneration occurs within the environment of muscle tissue. Intercellular cross-talk generates an interactive system of cellular networks that with the extracellular matrix and local, regional, and systemic influences, forms the larger gestalt of the satellite cell niche. Regenerative potential and adaptive plasticity are overlain by epigenetically regionalized responsiveness and contributions by myogenic, endothelial, and fibroadipogenic progenitors and inflammatory and metabolic processes. Muscle architecture is a living portrait of functional regulatory hierarchies, while cellular dynamics, physical activity, and muscle–tendon–bone biomechanics arbitrate regeneration. The scope of ongoing research—from molecules and exosomes to morphology and physiology—reveals compelling new concepts in muscle regeneration that will guide future discoveries for use in application to fitness, rehabilitation, and disease prevention and treatment. [ABSTRACT FROM AUTHOR]

A fortuitous auroral storm and a clear dark sky in a rural prairie setting allowed the authors to observe a Strong Thermal Emission Velocity Enhancement (aka STEVE) on a warm March night. It was a night of marvelous sights and new discovery. [ABSTRACT FROM AUTHOR]

The article focuses on the EngageAI Institute, originally the National Science Foundation AI Institute for Engaged Learning, designed for educators interested in using AI to enhance teaching skills. Topics include ethical considerations in artificial intelligence (AI)-augmented learning, a focus on STEM education for grades K–12, and efforts to increase participation among under-represented groups, such as women, people of color, and persons with disabilities.

The article focuses on the practical implementation of ethics in web design, providing a structured framework that moves beyond theoretical considerations. Topics include the need for ethical considerations in today's web design environment, an organized approach based on ethical theories, and a checklist of questions for designers to evaluate the impact of their decisions on both the designer and the end user.

The article focuses on artists suing artificial intelligence (AI) companies Midjourney and Stable Diffusion, alleging "industrial-level identity theft" for using their creative works without credit or compensation to train image-generating AI. It explores the ethical challenges posed by AI in creative fields, raising questions about derivative works, identity theft, and the management of recognition for original artists, cautioning readers about the broader implications of AI in culture.

The article focuses on importance of intellectual freedom to unleash creativity and discovery. Topics discussed include knowledge gained and the ideas of others to create even greater possibilities of insight and invention; financial supporters expect integrity in the process and unbiased results; and creativity and freedom to pursue even unpopular subjects are hampered.

The author comments on critical librarianship and how it interplays with intellectual freedom. Topics covered include impact of activism on the goal of the library to promote social consciousness, how the social activism of librarians affect their responsibility toward intellectual freedom, possible alienation of community members and library users due to social activism of librarians and the importance for librarians to respect the choices and ideology of individuals.

ABSTRACT Current research on skeletal muscle injury and regeneration highlights the crucial role of nerve-muscle interaction in the restoration of innervation during that process. Activities of muscle satellite or stem cells, recognized as the 'currency' of myogenic repair, have a pivotal role in these events, as shown by ongoing research. More recent investigation of myogenic signalling events reveals intriguing roles for semaphorin3A (Sema3A), secreted by activated satellite cells, in the muscle environment during development and regeneration. For example, Sema3A makes important contributions to regulating the formation of blood vessels, balancing bone formation and bone remodelling, and inflammation, and was recently implicated in the establishment of fibre-type distribution through effects on myosin heavy chain gene expression. This review highlights the active or potential contributions of satellite-cell-derived Sema3A to regulation of the processes of motor neurite ingrowth into a regenerating muscle bed. Successful restoration of functional innervation during muscle repair is essential; this review emphasizes the integrative role of satellite-cell biology in the progressive coordination of adaptive cellular and tissue responses during the injury-repair process in voluntary muscle. [ABSTRACT FROM AUTHOR]

The author argues that searching for information or products on the Internet has a censoring impact. Google, Bing, and Yahoo are cited as examples of major search engines. According to the author, private information are used by search engines to help screen or filter information. Also mentioned are the possibility of bias, use of recommendation technologies with the discovery software, and the information professional's responsibility in minimizing the censoring impact.

There is an acknowledged gap between the theory presented in university preparation programmes and the reality of classroom practice that has resulted in many secondary mathematics pre-service teachers failing to implement university-endorsed teaching strategies. Using responses to a questionnaire and interviews, this qualitative study examined the factors that support or inhibit secondary mathematics pre-service teachers’ implementation of problem-solving tasks during professional experience. The results showed that even though the majority of pre-service teachers reported having beliefs compatible with using problem-solving tasks, the secondary students’ ability, preparation time, and the cooperating teacher were key factors that inhibited pre-service teachers’ implementation of problem-solving tasks. It is recommended that pre-service teachers regularly visit classrooms to observe the evolving implementation of problem-solving approaches. Furthermore, cooperating teachers should be required to attend professional development before the professional experience so they understand the goals of the university preparation programme and have the requisite skills and knowledge to support the implementation of problem-solving tasks in learning mathematics. [ABSTRACT FROM AUTHOR]

The article offers the author's insights on privacy and the significance of personal data collection. Topics discussed include the use of Internet, confidentiality and control of information, and personal information marketing. She mentions that open network of information has become a product dispersing machine and economic data collection.

To attain a superior in vitro model of mature muscle fibers, we modified the established protocol for isolating single muscle fibers from rat skeletal muscle. Muscle fiber cultures with high viability were obtained using flexor digitorum brevis muscle and lasted for at least 7 days. We compared the expression levels of adult myosin heavy chain (MyHC) isoforms in these single muscle fibers with myotubes formed from myoblasts; isolated fibers contained markedly more abundant adult MyHC isoforms than myotubes. This muscle fiber model, therefore, will be useful for studying the various functions and cellular processes of mature muscles in vitro. [ABSTRACT FROM AUTHOR]

Mechanical perturbation triggers activation of resident myogenic stem cells to enter the cell cycle through a cascade of events including hepatocyte growth factor (HGF) release from its extracellular tethering and the subsequent presentation to signaling‐receptor c‐met. Here, we show that with aging, extracellular HGF undergoes tyrosine‐residue (Y) nitration and loses c‐met binding, thereby disturbing muscle homeostasis. Biochemical studies demonstrated that nitration/dysfunction is specific to HGF among other major growth factors and is characterized by its locations at Y198 and Y250 in c‐met‐binding domains. Direct‐immunofluorescence microscopy of lower hind limb muscles from three age groups of rat, provided direct in vivo evidence for age‐related increases in nitration of ECM‐bound HGF, preferentially stained for anti‐nitrated Y198 and Y250‐HGF mAbs (raised in‐house) in fast IIa and IIx myofibers. Overall, findings highlight inhibitory impacts of HGF nitration on myogenic stem cell dynamics, pioneering a cogent discussion for better understanding age‐related muscle atrophy and impaired regeneration with fibrosis (including sarcopenia and frailty). [ABSTRACT FROM AUTHOR]

Cell migration is central to development, wound healing, tissue regeneration, and immunity. Despite extensive knowledge of muscle regeneration, myoblast migration during regeneration is not well understood. C2C12 mouse myoblast migration and morphology were investigated using a triple-docking polydimethylsiloxane-based microfluidic device in which cells moved under gravity-driven laminar flow on uniform () collagen (CN), fibronectin (FN), or opposing gradients (CN-FN or FN-CN). In haptotaxis experiments, migration was faster on FN than on CN. At 10 h, cells were more elongated on FN-CN and migration was faster than on the CN-FN substrate. Net migration distance on FN-CN at 10 h was greater than on CN-FN, as cells rapidly entered the channel as a larger population (bulk-cell movement, wave 1). Hepatocyte growth factor (HGF) stimulated rapid chemotaxis on FN but not CN, increasing migration speed at 10 h early in the channel at low HGF in a steep HGF gradient. HGF accelerated migration on FN and bulk-cell movement on both uniform substrates. An HGF gradient also slowed cells in wave 2 moving on FN-CN, not CN-FN. Both opposing-gradient substrates affected the shape, speed, and net distance of migrating cells. Gradient and uniform configurations of HGF and substrate differentially influenced migration behavior. Therefore, haptotaxis substrate configuration potently modifies myoblast chemotaxis by HGF. Innovative microfluidic experiments advance our understanding of intricate complexities of myoblast migration. Findings can be leveraged to engineer muscle-tissue volumes for transplantation after serious injury. New analytical approaches may generate broader insights into cell migration.. [ABSTRACT FROM AUTHOR]

This document is the cover legend for an article titled "Age-related nitration/dysfunction of myogenic stem cell activator HGF" published in the journal Aging Cell. The article, authored by Alaa Elgaabari et al., explores the impact of aging on the function of a protein called HGF, which is involved in the activation of stem cells responsible for muscle regeneration. The research suggests that age-related nitration of HGF may contribute to the decline in muscle regeneration observed in older individuals. The article includes a list of all the authors involved in the study. [Extracted from the article]

R3710 --> Natural extracellular matrices made from cultured cells or tissues, are tissue and cell specific, and critical in tissue engineering and cellular applications. This study focused on the effects of a more naturally produced substrate, made by myotubes differentiated within a device channel, on migration and proliferation (haptotaxis) of a second set of cells (set2) loaded into the device. First, four different microfluidic devices were designed with pillars in either an offset pattern or aligned rows along the channel to investigate the myotube formation. C2C12 cells preloaded with Hoechst stain to label DNA (set1 cells), were loaded into device channels in medium with 2% serum to induce differentiation. Results showed that in devices with aligned rows, cells were more concentrated toward pillars, and their distance from a pillar was smaller than for cells in devices with offset rows of pillars. An average of 20‐30 set2 cells was tracked over 10 hours, by image capture every 2 hours in the 3 or 4 channels of each device. Results were compiled in Excel and analyzed by multi‐way ANOVAs using Jamovi software. Minimum distance to a pillar occurred rapidly, at day 0 for all four devices and increased over time. After allowing set1 cells to differentiate for 5 days, prestained set2 cells were loaded. The nucleus position of set2 cells was categorized as located nearest to one of four places in the migration channel: the nucleus of a set1 cell, an extension of a set1 cell, a pillar, or the device‐channel wall. Results showed that a 3‐channel device with offset rows of pillars was best able to lead set1 cells to form and align myotubes in the channel and then attract the most set2 cells to nuclei of those set1 cells. Since cellular proximity is critical to myotube formation and set 2 cells were closer to the set1 nuclei than to device pillars over 10 hours imaging. Differences in flow rate among the four devices suggest that the pillars' orientation, channel dimensions, and initial velocity are factors that influenced behavioural variations among set1 cells from the time of loading to the end of the 5‐day differentiation period. Experiments in devices that were precoated with a fibronectin substrate showed that fibronectin shortened the time to confluency of set1 cells by about 2 days. Perfusion of set1 cells after 5 days of differentiation with an RGD inhibitor ((Arg‐Gly‐Asp) peptide) of fibronectin binding to integrins, induced a significant shift in the behavior of set2 cells toward proximity to set1 nuclei, whereas without RGD, set2 cells moved toward a device pillar. Additional experiments targeting processes during the fibronectin signaling in migration are in progress to further explore mechanism targeted by variations in device design that affect cell behavior or movement. Further study of cellular taxis should provide clues to identifying a device that would best create a muscle by promoting muscle fiber growth (by fusion of set2 to set1 cells) or in the longer term, induce set2 cells to become quiescent satellite (stem) cells. [ABSTRACT FROM AUTHOR]

Purpose: Resistance exercise induces muscle growth and is an important treatment for age-related losses in muscle mass and strength. Myokines are hypothesized as a signal conveying physiological information to skeletal muscle, possibly to "fine-tune" other regulatory pathways. While myokines are released from skeletal muscle following contraction, their role in increasing muscle mass and strength in response to resistance exercise or training is not established. Recent research identified both local and systemic release of myokines after an acute bout of resistance exercise. However, it is not known whether myokines with putative anabolic function are mechanistically involved in producing muscle hypertrophy after resistance exercise. Further, nitric oxide (NO), an important mediator of muscle stem cell activation, upregulates the expression of certain myokine genes in skeletal muscle.Method: In the systemic context of complex hypertrophic signaling, this review: (1) summarizes literature on several well-recognized, representative myokines with anabolic potential; (2) explores the potential mechanistic role of myokines in skeletal muscle hypertrophy; and (3) identifies future research required to advance our understanding of myokine anabolism specifically in skeletal muscle.Result: This review establishes a link between myokines and NO production, and emphasizes the importance of considering systemic release of potential anabolic myokines during resistance exercise as complementary to other signals that promote hypertrophy.Conclusion: Investigating adaptations to resistance exercise in aging opens a novel avenue of interdisciplinary research into myokines and NO metabolites during resistance exercise, with the longer-term goal to improve muscle health in daily living, aging, and rehabilitation. [ABSTRACT FROM AUTHOR]

• The Foundation for the Accreditation of Cellular Therapy (FACT) requires accredited programs to assess patient outcomes, which should meet expected ranges. • Continued 1-year survival that is lower than expected can affect FACT accreditation. • Programs that do not meet expected survival must implement corrective actions. • FACT provides assurance that programs review and improve patient outcomes. The rapid evolution of blood and marrow transplantation (BMT), coupled with diverse outcomes associated with heterogeneous groups of patients, led to the formation of 2 important organizations early in the development of the field: the Center for International Blood and Marrow Transplant Research (CIBMTR) and the Foundation for the Accreditation of Cellular Therapy (FACT). These organizations have addressed 2 of the 9 elements identified by the National Quality Strategy (NQS) for achieving better health care, more affordable care, and healthy people and communities: a registry that promotes improvement of care and accreditation based on quality standards. More recently, a federally mandated database in the United States addresses the third element of the NQS: public reporting of treatment results. Here we describe the current process by which FACT incorporates patient outcomes reported by the CIBMTR into standards for accreditation, the requirements for accredited programs with performance below expected outcomes to maintain accreditation, and preliminary findings of an assessment of corrective action plans intended to improve outcomes. [ABSTRACT FROM AUTHOR]

Using growth modeling, this study examined trajectories of 'switching on' (aspirations) and 'switching off' (disengagement) in mathematics across middle school and high school. In addition, guided by principles under expectancy-value theory, the study sought to determine the extent to which patterns of growth differed by motivation (self-efficacy and valuing) and socio-educational attributes (gender, language background, and achievement). The sample comprised 194 students from four schools who participated in three rounds of data collection across five academic years of their schooling, spanning middle school and high school. In the main, mathematics aspirations declined over time while mathematics disengagement increased. However, initial levels of aspirations and disengagement and their rates of change over time were impacted by motivational and socio-educational factors. Salient findings and their implications for educational assessment and practice are discussed. [ABSTRACT FROM AUTHOR]

Introduction: Rotator-cuff injury (RCI) represents 50% of shoulder injuries, and prevalence increases with age. Even with successful tendon repair, muscle and joint function may not return.Methods: To explore the dysfunction, supraspinatus and ipsilateral deltoid (control) muscles were biopsied during arthroscopic RCI repair for pair-wise histological and protein-expression studies.Results: Supraspinatus showed fiber atrophy (P <  0.0001), fibrosis (by Sirius Red, P = 0.05), reduced vascular density (P <  0.001), and a lower proportion of slow fibers (P <  0.0001) compared with the ipsilateral control muscle. There were also higher levels of atrogin-1 (P = 0.05), vascular endothelial growth factor (VEGF, P <  0.01), and dystrophin (P <  0.008, relative to fiber diameter) versus control.Conclusions: Adaptive changes in vascular endothelial growth factor and dystrophin were likely associated with reduced vascular supply, fatigue resistance, and fibrosis, accompanied by disuse atrophy from mechanical unloading of supraspinatus after tendon tear. Treatment to promote growth and vascularity in atrophic supraspinatus muscle may help improve functional outcome after surgical repair. Muscle Nerve 55: 715-726, 2017. [ABSTRACT FROM AUTHOR]

Background: Rotator-cuff injury (RCI) is common and painful; even after surgery, joint stability and function may not recover. Relative contributions to atrophy from disuse, fibrosis, denervation, and satellite-cell responsiveness to activating stimuli are not known. Methods and Findings: Potential contributions of denervation and disrupted satellite cell responses to growth signals were examined in supraspinatus (SS) and control (ipsilateral deltoid) muscles biopsied from participants with RCI (N = 27). Biopsies were prepared for explant culture (to study satellite cell activity), immunostained to localize Pax7, BrdU, and Semaphorin 3A in satellite cells, sectioning to study blood vessel density, and western blotting to measure the fetal (γ) subunit of acetylcholine receptor (γ-AchR). Principal component analysis (PCA) for 35 parameters extracted components identified variables that contributed most to variability in the dataset. γ-AchR was higher in SS than control, indicating denervation. Satellite cells in SS had a low baseline level of activity (Pax7+ cells labelled in S-phase) versus control; only satellite cells in SS showed increased proliferative activity after nitric oxide-donor treatment. Interestingly, satellite cell localization of Semaphorin 3A, a neuro-chemorepellent, was greater in SS (consistent with fiber denervation) than control muscle at baseline. PCAs extracted components including fiber atrophy, satellite cell activity, fibrosis, atrogin-1, smoking status, vascular density, γAchR, and the time between symptoms and surgery. Use of deltoid as a control for SS was supported by PCA findings since “muscle” was not extracted as a variable in the first two principal components. SS muscle in RCI is therefore atrophic, denervated, and fibrotic, and has satellite cells that respond to activating stimuli. Conclusions: Since SS satellite cells can be activated in culture, a NO-donor drug combined with stretching could promote muscle growth and improve functional outcome after RCI. PCAs suggest indices including satellite cell responsiveness, atrogin-1, atrophy, and innervation may predict surgical outcome. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease with a 5-year survival rate of 4%. A key hallmark of PDAC is extensive stromal involvement, which makes capturing precise tumor-specific molecular information difficult. Here we have overcome this problem by applying blind source separation to a diverse collection of PDAC gene expression microarray data, including data from primary tumor, metastatic and normal samples. By digitally separating tumor, stromal and normal gene expression, we have identified and validated two tumor subtypes, including a 'basal-like' subtype that has worse outcome and is molecularly similar to basal tumors in bladder and breast cancers. Furthermore, we define 'normal' and 'activated' stromal subtypes, which are independently prognostic. Our results provide new insights into the molecular composition of PDAC, which may be used to tailor therapies or provide decision support in a clinical setting where the choice and timing of therapies are critical. [ABSTRACT FROM AUTHOR]

The high frequency of poor outcome and chronic pain after surgical repair of shoulder rotator-cuff injury (RCI) prompted this study to explore the potential to amplify muscle regeneration using nitric oxide (NO)- based treatment. After preoperative magnetic resonance imaging (MRI), biopsies of supraspinatus and ipsilateral deltoid (as a control) were collected during reparative surgery for RCI. Muscle fiber diameter, the pattern of neuromuscular junctions observed with alphabungarotoxin staining, and the γ:ε subunit ratio of acetylcholine receptors in Western blots were examined in tandem with experiments to determine the in vitro responsiveness of muscle satellite cells to activation (indicated by uptake of bromodeoxyuridine, BrdU) by the NO-donor drug, isosorbide dinitrate (ISDN). Consistent with MRI findings of supraspinatus atrophy (reduced occupation ratio and tangent sign), fiber diameter was lower in supraspinatus than in deltoid. ISDN induced a significant increase over baseline (up to 1.8-fold), in the proportion of BrdU+ (activated) Pax7+ satellite cells in supraspinatus, but not in deltoid, after 40 h in culture. The novel application of denervation indices revealed a trend for supraspinatus muscle to have a higher γ:ε subunit ratio than deltoid (P _ 0.13); this ratio inversely with both occupancy ratio (P < 0.05) and the proportion of clusters at neuromuscular junctions (P = 0.05). Results implicate possible supraspinatus denervation in RCI and suggest NO-donor treatment has potential to promote growth in atrophic supraspinatus muscle after RCI and improve functional outcome. [ABSTRACT FROM AUTHOR]

Regenerative mechanisms that regulate intramuscular motor innervation are thought to reside in the spatiotemporal expression of axon-guidance molecules. Our previous studies proposed an unexplored role of resident myogenic stem cell (satellite cell)-derived myoblasts as a key presenter of a secreted neural chemorepellent semaphorin 3A (Sema3A); hepatocyte growth factor ( HGF) and basic fibroblast growth factor ( FGF2) triggered its expression exclusively at the early differentiation phase. In order to advance this concept, the present study described that transmembrane heparan/chondroitin sulfate proteoglycans syndecan-2, 4 may be the plausible receptor candidates for HGF and FGF2 to signal Sema3A expression. Results showed that mRNA expression of syndecan-2, 4 was abundant (two magnitudes higher than syndecan-1, 3) in early-differentiated myoblasts and their in vitro knockdown diminished the HGF/ FGF2-induced expression of Sema3A down to a baseline level. Pretreatment with heparitinase and chondroitinase ABC decreased the HGF and FGF2 responses, respectively, in non-knockdown cultures, supporting a possible model that HGF and FGF2 may bind to heparan and chondroitin sulfate chains of syndecan-2, 4 to signal Sema3A expression. The findings, therefore, extend our understanding that HGF/ FGF2-syndecan-2, 4 association may stimulate a burst of Sema3A secretion by myoblasts recruited to the site of muscle injury; this would ensure a coordinated delay in the attachment of motoneuron terminals onto fibers early in muscle regeneration, and thus synchronize the recovery of muscle fiber integrity and the early resolution of inflammation after injury with reinnervation toward functional recovery. [ABSTRACT FROM AUTHOR]

A healthy skeletal muscle mass is essential in attenuating the complications of obesity. Importantly, healthy muscle function is maintained through adequate repair following overuse and injury. The purpose of this study was to investigate the impact of diet-induced obesity ( DIO) on skeletal muscle repair and the functionality of the muscle satellite cell ( SC) population. Male C57 BL/6J mice were fed a standard chow or high-fat diet (60% kcal fat; DIO) for 8 weeks. Muscles from DIO mice subjected to cardiotoxin injury displayed attenuated muscle regeneration, as indicated by prolonged necrosis, delayed expression of MyoD and Myogenin, elevated collagen content, and persistent embryonic myosin heavy chain expression. While no significant differences in SC content were observed, SCs from DIO muscles did not activate normally nor did they respond to exogenous hepatocyte growth factor ( HGF) despite similar receptor ( cMet) density. Furthermore, HGF release from crushed muscle was significantly less than that from muscles of chow fed mice. This study demonstrates that deficits in muscle repair are present in DIO, and the impairments in the functionality of the muscle SC population as a result of altered HGF/c-met signaling are contributors to the delayed regeneration. [ABSTRACT FROM AUTHOR]

A recent study demonstrated a positive effect of apple polyphenol (APP) intake on muscle endurance of young-adult animals. While an enhancement of lipid metabolism may be responsible, in part, for the improvement, the contributing mechanisms still need clarification. Here we show that an 8-week intake of 5% (w/w) APP in the diet, up-regulates two features related to fiber type: the ratio of myosin heavy chain (MyHC) type IIx/IIb and myoglobin protein expression in plantaris muscle of 9-week-old male Fischer F344 rats compared to pair-fed controls (P < 0.05). Results were demonstrated by our SDS-PAGE system specialized for MyHC isoform separation and western blotting of whole muscles. Animal-growth profiles (food intake, body-weight gain, and internal-organ weights) did not differ between the control and 5% APP-fed animals (n = 9/group). Findings may account for the increase in fatigue resistance of lower hind limb muscles, as evidenced by a slower decline in the maximum isometric planter-flexion torque generated by a 100-s train of electrical stimulation of the tibial nerve. Additionally, the fatigue resistance was lower after 8 weeks of a 0.5% APP diet than after 5% APP, supporting an APP-dose dependency of the shift in fiber-type composition. Therefore, the present study highlights a promising contribution of dietary APP intake to increasing endurance based on fiber-type composition in rat muscle. Results may help in developing a novel strategy for application in animal sciences, and human sports and age-related health sciences. [ABSTRACT FROM AUTHOR]

This study of 1,601 students in the middle years of schooling (Grades 5-8, each student measured twice, 1 year apart) from 200 classrooms in 44 schools sought to identify factors explaining gains and declines in mathematics engagement at key transition points. In multilevel regression modeling, findings showed that compared with Grade 6 students (upper elementary; the reference category), students in Grades 7 (typically the first secondary school year) and 8 have significantly declined in mathematics engagement from their previous year. Notably, in further analyses, these declines were found to be related to student (particularly mathematics self-efficacy and valuing), home (parent valuing of mathematics and availability of a computer for mathematics), classroom (class-average achievement and perceived climate), and school (socio-economic status and ethnic composition) factors. Implications for research and practice are discussed. [ABSTRACT FROM PUBLISHER]

Regenerative mechanisms that regulate intramuscular motor innervation are thought to reside in the spatiotemporal expression of axon-guidance molecules. Our previous studies proposed a heretofore unexplored role of resident myogenic stem cell (satellite cell)-derived myoblasts as a key presenter of a secreted neural chemorepellent semaphorin 3A (Sema3A); hepatocyte growth factor (HGF) triggered its expression exclusively at the early-differentiation phase. In order to verify this concept, the present study was designed to clarify a paracrine source of HGF release. In vitro experiments demonstrated that activated anti-inflammatory macrophages (CD206-positive M2) produce HGF and thereby promote myoblast chemoattraction and Sema3A expression. Media from pro-inflammatory macrophage cultures (M1) did not show any significant effect. M2 also enhanced the expression of myoblast-differentiation markers in culture, and infiltrated predominantly at the early-differentiation phase (3–5 days post-injury); M2 were confirmed to produce HGF as monitored by in vivo/ex vivo immunocytochemistry of CD11b/CD206/HGF-positive cells and by HGF in situ hybridization of cardiotoxin- or crush-injured tibialis anterior muscle, respectively. These studies advance our understanding of the stage-specific activation of Sema3A expression signaling. Findings, therefore, encourage the idea that M2 contribute to spatiotemporal up-regulation of extracellular Sema3A concentrations by producing HGF that, in turn, stimulates a burst of Sema3A secretion by myoblasts that are recruited to site of injury. This model may ensure a coordinated delay in re-attachment of motoneuron terminals onto damaged fibers early in muscle regeneration, and thus synchronize the recovery of muscle-fiber integrity and the early resolution of inflammation after injury. [ABSTRACT FROM AUTHOR]

Dystrophin links the transmembrane dystrophin-glycoprotein complex to the actin cytoskeleton. We have shown that dystrophin-glycoprotein complex subunits are markers for airway smooth muscle phenotype maturation and together with caveolin-1, play an important role in calcium homeostasis. We tested if dystrophin affects phenotype maturation, tracheal contraction and lung physiology. We used dystrophin deficient Golden Retriever dogs (GRMD) and mdx mice vs healthy control animals in our approach. We found significant reduction of contractile protein markers: smooth muscle myosin heavy chain (smMHC) and calponin and reduced Ca2+ response to contractile agonist in dystrophin deficient cells. Immunocytochemistry revealed reduced stress fibers and number of smMHC positive cells in dystrophin-deficient cells, when compared to control. Immunoblot analysis of Akt1, GSK3β and mTOR phosphorylation further revealed that downstream PI3K signaling, which is essential for phenotype maturation, was suppressed in dystrophin deficient cell cultures. Tracheal rings from mdx mice showed significant reduction in the isometric contraction to methacholine (MCh) when compared to genetic control BL10ScSnJ mice (wild-type). In vivo lung function studies using a small animal ventilator revealed a significant reduction in peak airway resistance induced by maximum concentrations of inhaled MCh in mdx mice, while there was no change in other lung function parameters. These data show that the lack of dystrophin is associated with a concomitant suppression of ASM cell phenotype maturation in vitro, ASM contraction ex vivo and lung function in vivo, indicating that a linkage between the DGC and the actin cytoskeleton via dystrophin is a determinant of the phenotype and functional properties of ASM. [ABSTRACT FROM AUTHOR]

Irisin is a myokine primarily recognized for its effect on browning adipose tissue, however emerging evidence suggests irisin also has a role in regulating skeletal muscle hypertrophy. PURPOSE: The purpose of this study was to determine if age or training status results in a differing systemic irisin concentrations following acute blood-flow restricted (BFR) resistanceexercise. METHODS: Fifteen untrained males (Younger: 24.7 ± 3.9 yrs, n=8; Older: 68.3 ± 4.6 yrs, n = 7) performed a bout of full-body BFR resistance-exercise before and after twelve weeks of progressive full-body resistance exercise training. Blood samples were collected via venipuncture before, immediately after, and 3, 6, 24 and 48 hours post-BFR resistance-exercise. Samples were analyzed in duplicate to determine irisin concentration. RESULTS: A main effect for age (younger = 480.23 ± 34.2 pg/mL vs. older = 281.36 ± 36.57 pg/mL; p = 0.001) and interaction effect for training status x time (p = 0.02) were identified. No other main or interaction effects were noted (all p > 0.05). The concentration of irisin did not differ between any time points in the untrained condition, but differences were observed after completing twelve weeks of resistance training. In the trained condition, irisin decreased immediately post-BFR compared to baseline (Baseline = 413.13 ± 44.47 pg/mL vs. Post-BFR = 286.97 ± 47.76; p = 0.004). The concentration of irisin immediately post-BFR was also lower than 6 hours post-BFR (Post-BFR = 286.97 ± 47.76 pg/mL vs. 6-hours = 448.20 ± 47.54; p = 0.002). CONCLUSION: Older adults have a lower concentration of irisin before and after acute BFRE regardless of training status. These results suggest that the myokine irisin could contribute to differences in skeletal muscle hypertrophy response to resistance exercise between younger and older males. In the untrained condition, irisin does not respond to acute BFR, however in the trained condition irisin decreases immediately following BFR and then peaks by 6 hours of recovery. The training status of individuals alters the response of irisin to acute resistance training potentially manipulating the time course of downstream insulin-like growth factor-1 and myostatin which irisin is postulated to upregulate and downregulate, respectively. [ABSTRACT FROM AUTHOR]

R3277 --> To examine the role of Sema3A expression in satellite cells (SCs) and terminal Schwann cells (TSCs) in neuromuscular junction (NMJs) formation, expression was investigated during recovery from muscle‐ or nerve‐crush injuries in muscle from mice with a SC‐specific knockout of Sema3A. We tested the hypothesis that loss of SC‐specific Sema3A expression would disrupt TSC gene and protein expression after both injuries. Gene expression in synaptic areas was studied using RNAscope multiplex fluorescence in situ hybridisation (ISH, Advanced Cell Diagnostics) to examine TSCs (Sema3A, S100B, P75NGFR), Pax7+ SCs, and Westerns to assay proteins (Sema3A and S100B, and γAchR, related to denervation). Muscle from transgenics with tamoxifen‐induced conditional knockout, and two control groups (injured non‐knockouts and no‐surgery SC‐specific knockouts) were examined 14 and 21days after nerve crush and 21 and 35days after muscle crush (ethics approval A30‐142‐0 (Kyushu U) and F14‐15 UManitoba). Expression sites (number, area, and intensity) for Sema3A, S100B, P75NGFR and Pax7 mRNA were imaged, measured (Celleste software) and analyzed (ANOVA, linear regression, and Principal Component Analysis, PCA) as a function of regeneration time. After muscle crush, P75NGFR expression was higher in SC‐specific Sema3A knockout mice (days 21 and 35) than in non‐knockout controls (p<0.001 Tukey's, df=16) suggesting an increased number of TSCs. γAchR protein was highest at day 21 vs. controls (p<0.001 Tukey's df=32) and correlated to Pax7 intensity in SCs. S100B expression correlated with regeneration time (p<0.01, df=34). S100B protein decreased at day 21 (Tukey's, p<0.001), possibly due to loss of TSCs by out‐migration or cell death, or lack of S100B promotor activity. After nerve crush, P75NGFR expression was higher at day 21 in knockouts than in controls and correlated to Sema3A expression intensity. γAchR protein correlated with P75NGFR and Pax7 expression, indicating SCs increase after denervation or that Pax7 expression/SC increases. S100B and Sema3A proteins in non‐knockout controls were lower at day 14 after nerve injury (2‐way Anova, p<0.001) and increased at day 21 (p<0.001), changes not seen in SC‐specific Sema3A knockout mice. Combining all data for both injuries in PCAs, TSC sites (colocalized P75NGFR, Sema3A and S100B expression) increased with increased S100B and Sema3A proteins (Factors 1 and 2 accounted for 51.8% of variance). PCA of SC sites (overlap of Pax7, S100B, and Sema3A expression) showed Sema3A mRNA and protein and S100B accounted for 30.9% of variance in SCs. Loss of SC‐specific Sema3A expression accelerated denervation after muscle injury. PCAs showed TSC function depends on Sema3A and S100B in reinnervation. Results advance our understanding of synaptic interactions of TSCs and SCs in vivo. This complex interaction between TSCs and SCs during reinnervation and regeneration opens an important new aspect of nerve‐muscle interaction at the cellular level, with possible implications for diseases where those interactions decline, such as amyotrophic lateral sclerosis. [ABSTRACT FROM AUTHOR]

Our previous studies demonstrated that an 8-week intake of 5% (w/w) apple polyphenol (APP) in the diet improves muscle endurance of young-adult rats. In order to identify a lower limit of the dietary contribution of APP to the effect, the experiments were designed for lower-dose supplementation (8-week feeding of 0.5% APP in AIN-93G diet) to 12-week-old male Sprague-Dawley rats. Results clearly showed that the 0.5% APP diet significantly up-regulates slower myosin-heavy-chain (MyHC) isoform ratios (IIx and IIa relative to total MyHC) and myoglobin expression in lower hind-limb muscles examined ( P < 0.05). There was a trend to increased fatigue resistance detected from measurements of relative isometric plantar-flexion force torque generated by a stimulus train delivered to the tibial nerve ( F(98, 1372) = 1.246, P = 0.0574). Importantly, there was no significant difference in the animal body-phenotypes or locomotor activity shown as total moving distance in light and dark periods. Therefore, the present study encourages the notion that even low APP-intake may increase the proportions of fatigue-resistant myofibers, and has promise as a strategy for modifying performance in human sports and improving function in age-related muscle atrophy. [ABSTRACT FROM AUTHOR]