Single muscle fiber proteomics reveals unexpected mitochondrial specialization

Mammalian skeletal muscles are composed of multinucleated cells termed slow or fast fibers according to their contractile and metabolic properties. Here, we developed a high-sensitivity workflow to characterize the proteome of single fibers. Analysis of segments of the same fiber by traditional and unbiased proteomics methods yielded the same subtype assignment. We discovered novel subtype-specific features, most prominently mitochondrial specialization of fiber types in substrate utilization. The fiber type-resolved proteomes can be applied to a variety of physiological and pathological conditions and illustrate the utility of single cell type analysis for dissecting proteomic heterogeneity

Upper Second Molar Distalization with Clear Aligners: A Finite Element Study

Among orthodontists and scientists, in the last years, upper molar distalization has been a debated topic in the orthodontic aligner field. However, despite that few clinical studies have been published, no insights on aligners' biomechanics regarding this movement are available. The aim of this study was to assess, through finite element analysis, the force system resulting in the upper arch during second maxillary molar distalization with clear aligners and variable attachments settings. The average tooth distalization was found to be 0.029, with buccal flaring of the upper incisors in all attachment configurations. The mesial deformation of the aligner was registered to be 0.2 mm on average. Different pressure areas on the interface between aligners and upper molars were registered, with the mesial attachment surface to be directly involved when present. Periodontal ligament pressure was reported to range between 67 g/cm(2) and 132 g/cm(2). Configurations with rectangular attachments from second molar-to-canine and from first molar-to-canine present, in an in silico environment, almost equal efficiency in distalizing the upper second molar. However, attachments from the second molar to the canine are suggested to be adopted in clinical environments due to greater feasibility in everyday practice

Multi-aspect testing and ranking inference to quantify dimorphism in the cytoarchitecture of cerebellum of male, female and intersex individuals: a model applied to bovine brains.

The dimorphism among male, female and freemartin intersex bovines, focusing on the vermal lobules VIII and IX, was analyzed using a novel data analytics approach to quantify morphometric differences in the cytoarchitecture of digitalized sections of the cerebellum. This methodology consists of multivariate and multi-aspect testing for cytoarchitecture-ranking, based on neuronal cell complexity among populations defined by factors, such as sex, age or pathology. In this context, we computed a set of shape descriptors of the neural cell morphology, categorized them into three domains named size, regularity and density, respectively. The output and results of our methodology are multivariate in nature, allowing an in-depth analysis of the cytoarchitectonic organization and morphology of cells. Interestingly, the Purkinje neurons and the underlying granule cells revealed the same morphological pattern: female possessed larger, denser and more irregular neurons than males. In the Freemartin, Purkinje neurons showed an intermediate setting between males and females, while the granule cells were the largest, most regular and dense. This methodology could be a powerful instrument to carry out morphometric analysis providing robust bases for objective tissue screening, especially in the field of neurodegenerative pathologies

Non-responsive Dihydropteridine Reductase Deficiency

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Northern areas as refugia for temperate species under current climate warming: Atlantic salmon (Salmo salar L.) as a model in Northern Europe

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordIn this work, patterns of geographical genetic diversity in Atlantic salmon Salmo salar were studied across the whole Atlantic arc, as well as whether patterns (and thus genetic population structure) were affected by water temperatures. Salmo salar populations were here characterized using microsatellite loci and then analysed in the light of ocean surface temperature data from across the region. Analysis showed the presence of a latitudinal cline of genetic variability (higher in northern areas) and water temperatures (sea surface temperatures) determining genetic population structure (the latter in combination with genetic drift in southern populations). Under the current global change scenario, northern areas of Europe would constitute refuges for diversity in the future. This is effectively the inverse of what appears to have happened in glacial refugia during the last glacial maximum. From this perspective, the still abundant and large northern populations should be considered as precious as the small almost relict southern ones and perhaps protected. Careful management of the species, coordinated across countries and latitudes, is needed in order to avoid its extinction in Europe.J. L. Horreo was supported by a MINECO Spanish postdoctoral grant (“Juan de la CiervaIncorporación” (ref. IJCI-2015-23618). This work was funded by the European Union INTERREG IIIB programme (Atlantic Salmon Arc Project [ASAP], Project No. 040 and ASAP-2, Project No. 203). This study received additional funding from the Principality of Asturias Grants for Excellent Research (GRUPIN-2014-093) and the Contract CN-14-076

Multi-aspect testing and ranking inference to quantify dimorphism in the cytoarchitecture of cerebellum of male, female and intersex individuals: a model applied to bovine brains

The dimorphism among male, female and freemartin intersex bovines, focusing on the vermal lobules VIII and IX, was analyzed using a novel data analytics approach to quantify morphometric differences in the cytoarchitecture of digitalized sections of the cerebellum. This methodology consists of multivariate and multi-aspect testing for cytoarchitecture-ranking, based on neuronal cell complexity among populations defined by factors, such as sex, age or pathology. In this context, we computed a set of shape descriptors of the neural cell morphology, categorized them into three domains named size, regularity and density, respectively. The output and results of our methodology are multivariate in nature, allowing an in-depth analysis of the cytoarchitectonic organization and morphology of cells. Interestingly, the Purkinje neurons and the underlying granule cells revealed the same morphological pattern: female possessed larger, denser and more irregular neurons than males. In the Freemartin, Purkinje neurons showed an intermediate setting between males and females, while the granule cells were the largest, most regular and dense. This methodology could be a powerful instrument to carry out morphometric analysis providing robust bases for objective tissue screening, especially in the field of neurodegenerative pathologies

MRF4 negatively regulates adult skeletal muscle growth by repressing MEF2 activity

The myogenic regulatory factor MRF4 is highly expressed in adult skeletal muscle but its function is unknown. Here we show that Mrf4 knockdown in adult muscle induces hypertrophy and prevents denervation-induced atrophy. This effect is accompanied by increased protein synthesis and widespread activation of muscle-specific genes, many of which are targets of MEF2 transcription factors. MEF2-dependent genes represent the top-ranking gene set enriched after Mrf4 RNAi and a MEF2 reporter is inhibited by co-transfected MRF4 and activated by Mrf4 RNAi. The Mrf4 RNAi-dependent increase in fibre size is prevented by dominant negative MEF2, while constitutively active MEF2 is able to induce myofibre hypertrophy. The nuclear localization of the MEF2 corepressor HDAC4 is impaired by Mrf4 knockdown, suggesting that MRF4 acts by stabilizing a repressor complex that controls MEF2 activity. These findings open new perspectives in the search for therapeutic targets to prevent muscle wasting, in particular sarcopenia and cachexia

Protein multi-scale organization through graph partitioning and robustness analysis: Application to the myosin-myosin light chain interaction

Despite the recognized importance of the multi-scale spatio-temporal organization of proteins, most computational tools can only access a limited spectrum of time and spatial scales, thereby ignoring the effects on protein behavior of the intricate coupling between the different scales. Starting from a physico-chemical atomistic network of interactions that encodes the structure of the protein, we introduce a methodology based on multi-scale graph partitioning that can uncover partitions and levels of organization of proteins that span the whole range of scales, revealing biological features occurring at different levels of organization and tracking their effect across scales. Additionally, we introduce a measure of robustness to quantify the relevance of the partitions through the generation of biochemically-motivated surrogate random graph models. We apply the method to four distinct conformations of myosin tail interacting protein, a protein from the molecular motor of the malaria parasite, and study properties that have been experimentally addressed such as the closing mechanism, the presence of conserved clusters, and the identification through computational mutational analysis of key residues for binding.Comment: 13 pages, 7 Postscript figure