Determining factors for compensatory movements of the left arm and shoulder in violin playing

IntroductionDespite a large number of available ergonomic aids and recommendations regarding instrument positioning, violin players at any proficiency level still display a worrying incidence of task-specific complaints of incompletely understood etiology. Compensatory movement patterns of the left upper extremity form an integral part of violin playing. They are highly variable between players but remain understudied despite their relevance for task-specific health problems.MethodsThis study investigated individual position effects of the instrument and pre-existing biomechanical factors likely determining the degree of typical compensatory movements in the left upper extremity: (1) left elbow/upper arm adduction (“Reference Angle α”, deviation from the vertical axis), (2) shoulder elevation (“Coord x”, in mm), and (3) shoulder protraction (“Coord y”, in mm). In a group of healthy music students (N = 30, 15 m, 15 f, mean age = 22.5, SD = 2.6), “Reference Angle α” was measured by 3D motion capture analysis. “Coord x” and “Coord y” were assessed and ranked by a synchronized 2D HD video monitoring while performing a pre-defined 16-s tune under laboratory conditions. These three primary outcome variables were compared between four typical, standardized violin positions varying by their sideward orientation (“LatAx-CSP”) and/or inclination (“LoAx-HP”) by 30°, as well as the players’ usual playing position. Selected biomechanical hand parameter data were analyzed as co-factors according to Wagner’s Biomechanical Hand Measurement (BHM).ResultsMean “Reference Angle α” decreased significantly from 24.84 ± 2.67 to 18.61 ± 3.12° (p < 0.001), “Coord x” from 22.54 ± 7.417 to 4.75 ± 3.488 mm (p < 0.001), and “Coord y” from 5.66 ± 3.287 to 1.94 ± 1.901) mm (p < 0.001) when increasing LatAx-CSP and LoAx-HP by 30°. Concerning the biomechanical co-factors, “Reference Angle α”, “Coord y”, but not “Coord x”, were found to be significantly increased overall, with decreasing passive supination range (r = −0.307, p = <0.001 for “Passive Supination 250 g/16Ncm”, and r = −0.194, p = <0.001 for “Coord y”). Compensatory movements were larger during tune sections requiring high positioning of the left hand and when using the small finger.DiscussionResults may enable to adapt individually suitable instrument positions to minimize strenuous and potentially unhealthy compensation movements of the left upper extremity

Different shades of default mode disturbance in schizophrenia : Subnodal covariance estimation in structure and function

Schizophrenia is a devastating mental disease with an apparent disruption in the highly associative default mode network (DMN). Interplay between this canonical network and others probably contributes to goal-directed behavior so its disturbance is a candidate neural fingerprint underlying schizophrenia psychopathology. Previous research has reported both hyperconnectivity and hypoconnectivity within the DMN, and both increased and decreased DMN coupling with the multimodal saliency network (SN) and dorsal attention network (DAN). This study systematically revisited network disruption in patients with schizophrenia using data-derived network atlases and multivariate pattern-learning algorithms in a multisite dataset (n = 325). Resting-state fluctuations in unconstrained brain states were used to estimate functional connectivity, and local volume differences between individuals were used to estimate structural co-occurrence within and between the DMN, SN, and DAN. In brain structure and function, sparse inverse covariance estimates of network coupling were used to characterize healthy participants and patients with schizophrenia, and to identify statistically significant group differences. Evidence did not confirm that the backbone of the DMN was the primary driver of brain dysfunction in schizophrenia. Instead, functional and structural aberrations were frequently located outside of the DMN core, such as in the anterior temporoparietal junction and precuneus. Additionally, functional covariation analyses highlighted dysfunctional DMN-DAN coupling, while structural covariation results highlighted aberrant DMN-SN coupling. Our findings reframe the role of the DMN core and its relation to canonical networks in schizophrenia. We thus underline the importance of large-scale neural interactions as effective biomarkers and indicators of how to tailor psychiatric care to single patients

Independent evolution of sexual dimorphism and female-limited mimicry in swallowtail butterflies (Papilio dardanus and Papilio phorcas)

Several species of Swallowtail butterflies (genus Papilio) are Batesian mimics that express multiple mimetic female forms, while the males are monomorphic and non-mimetic. The evolution of such sex-limited mimicry may involve sexual dimorphism arising first and mimicry subsequently. Such a stepwise scenario through a non-mimetic, sexually dimorphic stage has been proposed for two closely related sexually dimorphic species; P. phorcas, a non-mimetic species with two female forms, and P. dardanus, a female-limited polymorphic mimetic species. Their close relationship indicates that female-limited polymorphism could be a shared derived character of the two species. Here we present a phylogenomic analysis of the dardanus group using 3964 nuclear loci and whole mitochondrial genomes showing that they are not sister species, and thus that the sexually-dimorphic state has arisen independently in the two species. Non-homology of the female polymorphism in both species is supported by population genetic analysis of engrailed, the presumed mimicry switch locus in P. dardanus. McDonald-Kreitman tests performed on SNPs in engrailed showed the signature of balancing selection in a polymorphic population of P. dardanus, but not in monomorphic populations, nor in the non-mimetic P. phorcas. Hence the wing polymorphism does not balance polymorphisms in engrailed in P. phorcas. Equally, unlike in P. dardanus, none of the SNPs in P. phorcas engrailed were associated with either female morph. We conclude that sexual dimorphism due to female polymorphism evolved independently in both species from monomorphic, non-mimetic states. While sexual selection may drive male-female dimorphism in non-mimetic species, in mimetic Papilios natural selection for protection from predators in females is an alternative route to sexual dimorphism

Massive Genomic Decay in Serratia symbiotica, a Recently Evolved Symbiont of Aphids

All vertically transmitted bacterial symbionts undergo a process of genome reduction over time, resulting in tiny, gene-dense genomes. Comparison of genomes of ancient bacterial symbionts gives only limited information about the early stages in the transition from a free-living to symbiotic lifestyle because many changes become obscured over time. Here, we present the genome sequence for the recently evolved aphid symbiont Serratia symbiotica. The S. symbiotica genome exhibits several of the hallmarks of genome evolution observed in more ancient symbionts, including elevated rates of evolution and reduction in genome size. The genome also shows evidence for massive genomic decay compared with free-living relatives in the same genus of bacteria, including large deletions, many pseudogenes, and a slew of rearrangements, perhaps promoted by mobile DNA. Annotation of pseudogenes allowed examination of the past and current metabolic capabilities of S. symbiotica and revealed a somewhat random process of gene inactivation with respect to function. Analysis of mutational patterns showed that deletions are more common in neutral DNA. The S. symbiotica genome provides a rare opportunity to study genome evolution in a recently derived heritable symbiont

Model SNP development for complex genomes based on hexaploid oat using high-throughput 454 sequencing technology

<p>Abstract</p> <p>Background</p> <p>Genetic markers are pivotal to modern genomics research; however, discovery and genotyping of molecular markers in oat has been hindered by the size and complexity of the genome, and by a scarcity of sequence data. The purpose of this study was to generate oat expressed sequence tag (EST) information, develop a bioinformatics pipeline for SNP discovery, and establish a method for rapid, cost-effective, and straightforward genotyping of SNP markers in complex polyploid genomes such as oat.</p> <p>Results</p> <p>Based on cDNA libraries of four cultivated oat genotypes, approximately 127,000 contigs were assembled from approximately one million Roche 454 sequence reads. Contigs were filtered through a novel bioinformatics pipeline to eliminate ambiguous polymorphism caused by subgenome homology, and 96 <it>in silico </it>SNPs were selected from 9,448 candidate loci for validation using high-resolution melting (HRM) analysis. Of these, 52 (54%) were polymorphic between parents of the Ogle1040 × TAM O-301 (OT) mapping population, with 48 segregating as single Mendelian loci, and 44 being placed on the existing OT linkage map. Ogle and TAM amplicons from 12 primers were sequenced for SNP validation, revealing complex polymorphism in seven amplicons but general sequence conservation within SNP loci. Whole-amplicon interrogation with HRM revealed insertions, deletions, and heterozygotes in secondary oat germplasm pools, generating multiple alleles at some primer targets. To validate marker utility, 36 SNP assays were used to evaluate the genetic diversity of 34 diverse oat genotypes. Dendrogram clusters corresponded generally to known genome composition and genetic ancestry.</p> <p>Conclusions</p> <p>The high-throughput SNP discovery pipeline presented here is a rapid and effective method for identification of polymorphic SNP alleles in the oat genome. The current-generation HRM system is a simple and highly-informative platform for SNP genotyping. These techniques provide a model for SNP discovery and genotyping in other species with complex and poorly-characterized genomes.</p

Pyrosequencing-Based Comparative Genome Analysis of Vibrio vulnificus Environmental Isolates

Between 1996 and 2006, the US Centers for Disease Control reported that the only category of food-borne infections increasing in frequency were those caused by members of the genus Vibrio. The Gram-negative bacterium Vibrio vulnificus is a ubiquitous inhabitant of estuarine waters, and is the number one cause of seafood-related deaths in the US. Many V. vulnificus isolates have been studied, and it has been shown that two genetically distinct subtypes, distinguished by 16S rDNA and other gene polymorphisms, are associated predominantly with either environmental or clinical isolation. While local genetic differences between the subtypes have been probed, only the genomes of clinical isolates have so far been completely sequenced. In order to better understand V. vulnificus as an agent of disease and to identify the molecular components of its virulence mechanisms, we have completed whole genome shotgun sequencing of three diverse environmental genotypes using a pyrosequencing approach. V. vulnificus strain JY1305 was sequenced to a depth of 33×, and strains E64MW and JY1701 were sequenced to lesser depth, covering approximately 99.9% of each genome. We have performed a comparative analysis of these sequences against the previously published sequences of three V. vulnificus clinical isolates. We find that the genome of V. vulnificus is dynamic, with 1.27% of genes in the C-genotype genomes not found in the E- genotype genomes. We identified key genes that differentiate between the genomes of the clinical and environmental genotypes. 167 genes were found to be specifically associated with environmental genotypes and 278 genes with clinical genotypes. Genes specific to the clinical strains include components of sialic acid catabolism, mannitol fermentation, and a component of a Type IV secretory pathway VirB4, as well as several other genes with potential significance for human virulence. Genes specific to environmental strains included several that may have implications for the balance between self-preservation under stress and nutritional competence

First Transcriptome of the Testis-Vas Deferens-Male Accessory Gland and Proteome of the Spermatophore from Dermacentor variabilis (Acari: Ixodidae)

Ticks are important vectors of numerous human diseases and animal diseases. Feeding stimulates spermatogenesis, mating and insemination of male factors that trigger female reproduction. The physiology of male reproduction and its regulation of female development are essentially a black box. Several transcriptomes have catalogued expression of tick genes in the salivary glands, synganglion and midgut but no comprehensive investigation has addressed male reproduction and mating. Consequently, a new global approach using transcriptomics, proteomics, and quantitative gene expression is needed to understand male reproduction and stimulation of female reproduction

A Critical Analysis of Atoh7 (Math5) mRNA Splicing in the Developing Mouse Retina

The Math5 (Atoh7) gene is transiently expressed during retinogenesis by progenitors exiting mitosis, and is essential for ganglion cell (RGC) development. Math5 contains a single exon, and its 1.7 kb mRNA encodes a 149-aa polypeptide. Mouse Math5 mutants have essentially no RGCs or optic nerves. Given the importance of this gene in retinal development, we thoroughly investigated the possibility of Math5 mRNA splicing by Northern blot, 3′RACE, RNase protection assays, and RT-PCR, using RNAs extracted from embryonic eyes and adult cerebellum, or transcribed in vitro from cDNA clones. Because Math5 mRNA contains an elevated G+C content, we used graded concentrations of betaine, an isostabilizing agent that disrupts secondary structure. Although ∼10% of cerebellar Math5 RNAs are spliced, truncating the polypeptide, our results show few, if any, spliced Math5 transcripts exist in the developing retina (<1%). Rare deleted cDNAs do arise via RT-mediated RNA template switching in vitro, and are selectively amplified during PCR. These data differ starkly from a recent study (Kanadia and Cepko 2010), which concluded that the vast majority of Math5 and other bHLH transcripts are spliced to generate noncoding RNAs. Our findings clarify the architecture of the Math5 gene and its mechanism of action. These results have implications for all members of the bHLH gene family, for any gene that is alternatively spliced, and for the interpretation of all RT-PCR experiments

シェリング哲学の研究 (その1) : 自然哲学から同一哲学への展開

textabstractWhile they account for one-fifth of new cancer cases, rare cancers are difficult to study. A higher than average degree of uncertainty should be accommodated for clinical as well as for population-based decision making. Rules of rational decision making in conditions of uncertainty should be rigorously followed and would need widely informative clinical trials. In principle, any piece of new evidence would need to be exploited in rare cancers. Methodologies to explicitly weigh and combine all the available evidence should be refined, and the Bayesian logic can be instrumental to this end. Likewise, Bayesian-design trials may help optimize the low number of patients liable to be enrolled in clinical studies on rare cancers, as well as adaptive trials in general, with their inherent potential of flexibility when properly applied. While clinical studies are the mainstay to test hypotheses, the potential of electronic patient records should be exploited to generate new hypotheses, to create external controls for future studies (when internal controls are unpractical), to study effectiveness of new treatments in real conditions. Framework study protocols in specific rare cancers to stepwisely test sets of new agents, as from the early post-phase I development stage, should be encouraged. Also the compassionate and the off-label settings should be exploited to generate new evidence, and flexible regulatory innovations such as adaptive licensing could convey new agents early to rare cancer patients, while generating evidence. Though validation of surrogate end points is problematic in rare cancers, the use of an updated notion of tumor response may be of great value in the single patient to optimize the use of therapies, all the more the new ones. Disease-based communities, involving clinicians and patients, should be regularly consulted by regulatory bodies when setting their policies on drug approval and reimbursement in specific rare cancers