Statin-induced increases in atrophy gene expression occur independently of changes in PGC1α protein and mitochondrial content

One serious side effect of statin drugs is skeletal muscle myopathy. Although the mechanism(s) responsible for statin myopathy remains to be fully determined, an increase in muscle atrophy gene expression and changes in mitochondrial content and/or function have been proposed to play a role. In this study, we examined the relationship between statin-induced expression of muscle atrophy genes, regulators of mitochondrial biogenesis, and markers of mitochondrial content in slow- (ST) and fast-twitch (FT) rat skeletal muscles. Male Sprague Dawley rats were treated with simvastatin (60 or 80 mg·kg(-1)·day(-1)) or vehicle control via oral gavage for 14 days. In the absence of overt muscle damage, simvastatin treatment induced an increase in atrogin-1, MuRF1 and myostatin mRNA expression; however, these were not associated with changes in peroxisome proliferator gamma co-activator 1 alpha (PGC-1α) protein or markers of mitochondrial content. Simvastatin did, however, increase neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS) and AMPK α-subunit protein expression, and tended to increase total NOS activity, in FT but not ST muscles. Furthermore, simvastatin induced a decrease in β-hydroxyacyl CoA dehydrogenase (β-HAD) activity only in FT muscles. These findings suggest that the statin-induced activation of muscle atrophy genes occurs independent of changes in PGC-1α protein and mitochondrial content. Moreover, muscle-specific increases in NOS expression and possibly NO production, and decreases in fatty acid oxidation, could contribute to the previously reported development of overt statin-induced muscle damage in FT muscles

Recovering from failure by asking for help

Robots inevitably fail, often without the ability to recover autonomously. We demonstrate an approach for enabling a robot to recover from failures by communicating its need for specific help to a human partner using natural language. Our approach automatically detects failures, then generates targeted spoken-language requests for help such as “Please give me the white table leg that is on the black table.” Once the human partner has repaired the failure condition, the system resumes full autonomy. We present a novel inverse semantics algorithm for generating effective help requests. In contrast to forward semantic models that interpret natural language in terms of robot actions and perception, our inverse semantics algorithm generates requests by emulating the human’s ability to interpret a request using the Generalized Grounding Graph (G[superscript 3]) framework. To assess the effectiveness of our approach, we present a corpus-based online evaluation, as well as an end-to-end user study, demonstrating that our approach increases the effectiveness of human interventions compared to static requests for help.Boeing CompanyU.S. Army Research Laboratory (Robotics Collaborative Technology Alliance

Diversity, host specialization, and geographic structure of filarial nematodes infecting Malagasy bats

We investigated filarial infection in Malagasy bats to gain insights into the diversity of these parasites and explore the factors shaping their distribution. Samples were obtained from 947 individual bats collected from 52 sites on Madagascar and representing 31 of the 44 species currently recognized on the island. Samples were screened for the presence of micro-and macro-parasites through both molecular and morphological approaches. Phylogenetic analyses showed that filarial diversity in Malagasy bats formed three main groups, the most common represented by Litomosa spp. infecting Miniopterus spp. (Miniopteridae); a second group infecting Pipistrellus cf. hesperidus (Vespertilionidae) embedded within the Litomosoides cluster, which is recognized herein for the first time from Madagascar; and a third group composed of lineages with no clear genetic relationship to both previously described filarial nematodes and found in M. griveaudi, Myotis goudoti, Neoromicia matroka (Vespertilionidae), Otomops madagascariensis (Molossidae), and Paratriaenops furculus (Hipposideridae). We further analyzed the infection rates and distribution pattern of Litomosa spp., which was the most diverse and prevalent filarial taxon in our sample. Filarial infection was disproportionally more common in males than females in Miniopterus spp., which might be explained by some aspect of roosting behavior of these cave-dwelling bats. We also found marked geographic structure in the three Litomosa clades, mainly linked to bioclimatic conditions rather than host-parasite associations. While this study demonstrates distinct patterns of filarial nematode infection in Malagasy bats and highlights potential drivers of associated geographic distributions, future work should focus on their alpha taxonomy and characterize arthropod vectors

Understanding the diagnosis and management of multisystem inflammatory syndrome in adults (MIS-A) in the UK: results of a national Delphi process.

Infection with SARS-CoV-2 may trigger a delayed hyper-inflammatory illness in children called paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS-TS). A similar syndrome is increasingly recognised in adults termed multisystem inflammatory syndrome in adults (MIS-A) and may present acutely to medical or surgical specialties with severe symptoms, such as acute abdominal pain or cardiogenic shock. No national guidelines exist in the UK for the management of MIS-A and there is limited evidence to guide treatment plans. We undertook a national Delphi process to elicit opinions from experts in hyperinflammation about the diagnosis and management of MIS-A with the dual aim of improving recognition and producing a management guideline. Colleagues in paediatrics successfully initiated a national consensus management document that facilitated regional multidisciplinary referral and follow-up pathways for children with PIMS-TS, and we propose a similar system be developed for adult patients across the UK. This would facilitate better recognition and treatment of MIS-A across the multiple specialties to which it may present as well as enable follow-up with specialty services post-discharge

Is relatively young age within a school year a risk factor for mental health problems and poor school performance? A population-based cross-sectional study of adolescents in Oslo, Norway

BACKGROUND: Several studies have shown that children who are relatively young within a school year are at greater risk for poorer school performance compared with their older peers. One study also reported that relative age within a school year is an independent risk factor for emotional and behavioral problems. The objective of this study was to test the hypothesis that relatively younger adolescents in the multiethnic population of Oslo have poorer school performance and more mental health problems than their relatively older classmates within the same school year. METHODS: This population-based cross-sectional study included all 10(th)-grade pupils enrolled in 2000 and 2001 in the city of Oslo. The participation rate was 88%. Of the 6,752 pupils in the study sample, 25% had a non-Norwegian background. Mental health problems were quantified using the abbreviated versions of Symptom Check List-25 (SCL-10) and the Strength and Difficulties Questionnaire (SDQ). Information on school performances and mental health problems were self-reported. We controlled for confounding factors including parental educational level, social support, gender, and ethnicity. RESULTS: The youngest one-third of pupils had significantly lower average school grades than the middle one-third and oldest one-third of their classmates (p < 0.001). Of the mental health problems identified in the questionnaires, the groups differed only on peer problems; the youngest one-third reported significantly more problems than the middle and oldest groups (p < 0.05). Age within a school year and gender showed significant interactions with total SDQ score, SDQ peer problems score, SDQ pro social score, and SCL-10 score. After stratifying for gender, the peer problem scores differed significantly between age groups only among boys. The SCL-10 score was significant, but only in girls and in the opposite direction to that expected, with the oldest pupils having significantly higher scores than the other two groups (p < 0.05). CONCLUSION: In adolescents from a multicultural city in Norway, relative age within a school year significantly influenced academic performance. In contrast to data from Great Britain, relative age within a school year was not an important risk factor for mental health problems in adolescents in Oslo

Muscle Fiber Type-Dependent Differences in the Regulation of Protein Synthesis

This study examined fiber type-dependent differences in the regulation of protein synthesis in individual muscle fibers found within the same whole muscle. Specifically, the in vivo SUrface SEnsing of Translation (SUnSET) methodology was used to measure protein synthesis in type 1, 2A, 2X and 2B fibers of the mouse plantaris muscle, in response to food deprivation (FD), and mechanical overload induced by synergist ablation (SA). The results show that 48 h of FD induced a greater decrease in protein synthesis in type 2X and 2B fibers compared to type 1 and 2A fibers. Type 2X and 2B fibers also had the largest FD-induced decrease in total S6 protein and Ser240/244 S6 phosphorylation, respectively. Moreover, only type 2X and 2B fibers displayed a FD-induced decrease in cross-sectional area (CSA). Ten days of SA also induced fiber type-dependent responses, with type 2B fibers having the smallest SA-induced increases in protein synthesis, CSA and Ser240/244 S6 phosphorylation, but the largest increase in total S6 protein. Embryonic myosin heavy chain (MHCEmb) positive fibers were also found in SA muscles and the protein synthesis rates, levels of S6 Ser240/244 phosphorylation, and total S6 protein content, were 3.6-, 6.1- and 2.9-fold greater than that found in fibers from control muscles, respectively. Overall, these results reveal differential responses in the regulation of protein synthesis and fiber size between fiber types found within the same whole muscle. Moreover, these findings demonstrate that changes found at the whole muscle level do not necessarily reflect changes in individual fiber types

Dark Matter from Minimal Flavor Violation

We consider theories of flavored dark matter, in which the dark matter particle is part of a multiplet transforming nontrivially under the flavor group of the Standard Model in a manner consistent with the principle of Minimal Flavor Violation (MFV). MFV automatically leads to the stability of the lightest state for a large number of flavor multiplets. If neutral, this particle is an excellent dark matter candidate. Furthermore, MFV implies specific patterns of mass splittings among the flavors of dark matter and governs the structure of the couplings between dark matter and ordinary particles, leading to a rich and predictive cosmology and phenomenology. We present an illustrative phenomenological study of an effective theory of a flavor SU(3)_Q triplet, gauge singlet scalar.Comment: 10 pages, 2 figures; v2: references added, minor changes to collider analysis, conclusions unchange

Better mental health in children of Vietnamese refugees compared with their Norwegian peers - a matter of cultural difference?

<p>Abstract</p> <p>Background</p> <p>There are conflicting results on whether immigrant children are at a heightened risk of mental health problems compared with native youth in the resettlement country.</p> <p>The objective of the study</p> <p>To compare the mental health of 94 Norwegian-born children from a community cohort of Vietnamese refugees, aged 4 - 18 years, with that of a Norwegian community sample.</p> <p>Methods</p> <p>The SDQ was completed by two types of informants; the children's self-reports, and the parents' reports, for comparison with Norwegian data from the Health Profiles for Children and Youth in the Akershus study.</p> <p>Results</p> <p>The self-perceived mental health of second-generation Vietnamese in Norway was better than that of their Norwegian compatriots, as assessed by the SDQ. In the Norwegian-Vietnamese group, both children and parents reported a higher level of functioning.</p> <p>Conclusion</p> <p>This surprising finding may result from the lower prevalence of mental distress in Norwegian-Vietnamese children compared with their Norwegian peers, or from biased reports and cultural differences in reporting emotional and behavioural problems. These findings may represent the positive results of the children's bi-cultural competencies.</p

Submillimeter Studies of Prestellar Cores and Protostars: Probing the Initial Conditions for Protostellar Collapse

Improving our understanding of the initial conditions and earliest stages of protostellar collapse is crucial to gain insight into the origin of stellar masses, multiple systems, and protoplanetary disks. Observationally, there are two complementary approaches to this problem: (1) studying the structure and kinematics of prestellar cores observed prior to protostar formation, and (2) studying the structure of young (e.g. Class 0) accreting protostars observed soon after point mass formation. We discuss recent advances made in this area thanks to (sub)millimeter mapping observations with large single-dish telescopes and interferometers. In particular, we argue that the beginning of protostellar collapse is much more violent in cluster-forming clouds than in regions of distributed star formation. Major breakthroughs are expected in this field from future large submillimeter instruments such as Herschel and ALMA.Comment: 12 pages, 9 figures, to appear in the proceedings of the conference "Chemistry as a Diagnostic of Star Formation" (C.L. Curry & M. Fich eds.

Primed T Cell Responses to Chemokines Are Regulated by the Immunoglobulin-Like Molecule CD31

CD31, an immunoglobulin-like molecule expressed by leukocytes and endothelial cells, is thought to contribute to the physiological regulation T cell homeostasis due to the presence of two immunotyrosine-based inhibitory motifs in its cytoplasmic tail. Indeed, loss of CD31 expression leads to uncontrolled T cell-mediated inflammation in a variety of experimental models of disease and certain CD31 polymorphisms correlate with increased disease severity in human graft-versus-host disease and atherosclerosis. The molecular mechanisms underlying CD31-mediated regulation of T cell responses have not yet been clarified. We here show that CD31-mediated signals attenuate T cell chemokinesis both in vitro and in vivo. This effect selectively affects activated/memory T lymphocytes, in which CD31 is clustered on the cell membrane where it segregates to the leading edge. We provide evidence that this molecular segregation, which does not occur in naïve T lymphocytes, might lead to cis-CD31 engagement on the same membrane and subsequent interference with the chemokine-induced PI3K/Akt signalling pathway. We propose that CD31-mediated modulation of memory T cell chemokinesis is a key mechanism by which this molecule contributes to the homeostatic regulation of effector T cell immunity