The occipital lateral plate mesoderm is a novel source for vertebrate neck musculature

In vertebrates, body musculature originates from somites, whereas head muscles originate from the cranial mesoderm. Neck muscles are located in the transition between these regions. We show that the chick occipital lateral plate mesoderm has myogenic capacity and gives rise to large muscles located in the neck and thorax. We present molecular and genetic evidence to show that these muscles not only have a unique origin, but additionally display a distinct temporal development, forming later than any other muscle group described to date. We further report that these muscles, found in the body of the animal, develop like head musculature rather than deploying the programme used by the trunk muscles. Using mouse genetics we reveal that these muscles are formed in trunk muscle mutants but are absent in head muscle mutants. In concordance with this conclusion, their connective tissue is neural crest in origin. Finally, we provide evidence that the mechanism by which these neck muscles develop is conserved in vertebrates

On the evolution of centrifugal instabilities within curved incompressible mixing layers

It is known that certain configurations which possess curvature are prone to a class of instabilities which their 'flat' counterparts will not support. The main thrust of the study of these centrifugal instabilities has concentrated on curved solid boundaries and their effect on the fluid motion. In this article attention is shifted towards a fluid-fluid interface observed within a curved incompressible mixing layer. Experimental evidence is available to support the conjecture that this situation may be subjected to centrifugal instabilities. The evolution of modes with wavelengths comparable with the layer's thickness is considered and the high Taylor/Gortler number regime is also discussed which characterizes the ultimate fate of the modes

On the force field optimisation of β -lactam cores using the force field Toolkit

When employing molecular dynamics (MD) simulations for computer-aided drug design, the quality of the used force fields is highly important. Here we present reparametrisations of the force fields for the core molecules from 9 different β-lactam classes, for which we utilized the force field Toolkit and Gaussian calculations. We focus on the parametrisation of the dihedral angles, with the goal of reproducing the optimised quantum geometry in MD simulations. Parameters taken from CGenFF turn out to be a good initial guess for the multiplicity of each dihedral angle, but the key to a successful parametrisation is found to lie in the phase shifts. Based on the optimised quantum geometry, we come up with a strategy for predicting the phase shifts prior to the dihedral potential fitting. This allows us to successfully parameterise 8 out of the 11 molecules studied here, while the remaining 3 molecules can also be parameterised with small adjustments. Our work highlights the importance of predicting the dihedral phase shifts in the ligand parametrisation protocol, and provides a simple yet valuable strategy for improving the process of parameterising force fields of drug-like molecules

A clustering property of highly-degenerate transcription factor binding sites in the mammalian genome

Transcription factor binding sites (TFBSs) are short DNA sequences interacting with transcription factors (TFs), which regulate gene expression. Due to the relatively short length of such binding sites, it is largely unclear how the specificity of protein–DNA interaction is achieved. Here, we have performed a genome-wide analysis of TFBS-like sequences for the transcriptional repressor, RE1 Silencing Transcription Factor (REST), as well as for several other representative mammalian TFs (c-myc, p53, HNF-1 and CREB). We find a nonrandom distribution of inexact sites for these TFs, referred to as highly-degenerate TFBSs, that are enriched around the cognate binding sites. Comparisons among human, mouse and rat orthologous promoters reveal that these highly-degenerate sites are conserved significantly more than expected by random chance, suggesting their positive selection during evolution. We propose that this arrangement provides a favorable genomic landscape for functional target site selection

Patella dislocation with vertical axis rotation: the "dorsal fin" patella.

A 44-year-old woman presented following minor trauma to her right knee. While dancing she externally rotated around a planted foot and felt sudden pain in her right knee. She presented with her knee locked in extension with a "dorsal fin" appearance of the soft tissues tented over the patella. This was diagnosed as a rare case of an intraarticular patella dislocation, which was rotated 90 degrees about the vertical axis. Closed reduction in the emergency room was unsuccessful but was achieved in theatre under general anaesthetic with muscle relaxation. Postreduction arthroscopy demonstrated that no osteochondral or soft tissue damage to the knee had been sustained. In patients presenting with a knee locked in extension with tenting of skin over the patella (the "dorsal fin" appearance), intra-articular patella dislocation should be suspected. Attempts to reduce vertical patella dislocations under sedation with excessive force or repeatedly without success should be avoided to prevent unnecessary damage to the patellofemoral joint. In this clinical situation we recommend closed reduction under general anaesthetic followed by immediate knee arthroscopy under the same anaesthetic to ensure that there is no chondral damage to the patella or femoral trochlea and to rule out an osteochondral fracture

Topological Analysis of Metabolic Networks Integrating Co-Segregating Transcriptomes and Metabolomes in Type 2 Diabetic Rat Congenic Series

Background: The genetic regulation of metabolic phenotypes (i.e., metabotypes) in type 2 diabetes mellitus is caused by complex organ-specific cellular mechanisms contributing to impaired insulin secretion and insulin resistance. Methods: We used systematic metabotyping by 1H NMR spectroscopy and genome-wide gene expression in white adipose tissue to map molecular phenotypes to genomic blocks associated with obesity and insulin secretion in a series of rat congenic strains derived from spontaneously diabetic Goto-Kakizaki (GK) and normoglycemic Brown-Norway (BN) rats. We implemented a network biology strategy approach to visualise shortest paths between metabolites and genes significantly associated with each genomic block. Results: Despite strong genomic similarities (95-99%) among congenics, each strain exhibited specific patterns of gene expression and metabotypes, reflecting metabolic consequences of series of linked genetic polymorphisms in the congenic intervals. We subsequently used the congenic panel to map quantitative trait loci underlying specific metabotypes (mQTL) and genome-wide expression traits (eQTL). Variation in key metabolites like glucose, succinate, lactate or 3-hydroxybutyrate, and second messenger precursors like inositol was associated with several independent genomic intervals, indicating functional redundancy in these regions. To navigate through the complexity of these association networks we mapped candidate genes and metabolites onto metabolic pathways and implemented a shortest path strategy to highlight potential mechanistic links between metabolites and transcripts at colocalized mQTLs and eQTLs. Minimizing shortest path length drove prioritization of biological validations by gene silencing. Conclusions: These results underline the importance of network-based integration of multilevel systems genetics datasets to improve understanding of the genetic architecture of metabotype and transcriptomic regulations and to characterize novel functional roles for genes determining tissue-specific metabolism

Plasma and Energetic Particle Behaviors During Asymmetric Magnetic Reconnection at the Magnetopause

The factors controlling asymmetric reconnection and the role of the cold plasma population in the reconnection process are two outstanding questions. We present a case study of multipoint Cluster observations demonstrating that the separatrix and flow boundary angles are greater on the magnetosheath than on the magnetospheric side of the magnetopause, probably due to the stronger density than magnetic field asymmetry at this boundary. The motion of cold plasmaspheric ions entering the reconnection region differs from that of warmer magnetosheath and magnetospheric ions. In contrast to the warmer ions, which are probably accelerated by reconnection in the diffusion region near the subsolar magnetopause, the colder ions are simply entrained by drifts at high latitudes on the recently reconnected magnetic field lines. This indicates that plasmaspheric ions can sometimes play only a very limited role in asymmetric reconnection, in contrast to previous simulation studies. Three cold ion populations (probably H+, He+, and O+) appear in the energy spectrum, consistent with ion acceleration to a common velocity

A theory of L1L^1-dissipative solvers for scalar conservation laws with discontinuous flux

We propose a general framework for the study of $L^1$ contractive semigroups of solutions to conservation laws with discontinuous flux. Developing the ideas of a number of preceding works we claim that the whole admissibility issue is reduced to the selection of a family of "elementary solutions", which are certain piecewise constant stationary weak solutions. We refer to such a family as a "germ". It is well known that (CL) admits many different $L^1$ contractive semigroups, some of which reflects different physical applications. We revisit a number of the existing admissibility (or entropy) conditions and identify the germs that underly these conditions. We devote specific attention to the anishing viscosity" germ, which is a way to express the "$\Gamma$-condition" of Diehl. For any given germ, we formulate "germ-based" admissibility conditions in the form of a trace condition on the flux discontinuity line $x=0$ (in the spirit of Vol'pert) and in the form of a family of global entropy inequalities (following Kruzhkov and Carrillo). We characterize those germs that lead to the $L^1$-contraction property for the associated admissible solutions. Our approach offers a streamlined and unifying perspective on many of the known entropy conditions, making it possible to recover earlier uniqueness results under weaker conditions than before, and to provide new results for other less studied problems. Several strategies for proving the existence of admissible solutions are discussed, and existence results are given for fluxes satisfying some additional conditions. These are based on convergence results either for the vanishing viscosity method (with standard viscosity or with specific viscosities "adapted" to the choice of a germ), or for specific germ-adapted finite volume schemes

WDR19 : An ancient, retrograde, intraflagellar ciliary protein is mutated in autosomal recessive retinitis pigmentosa and in Senior‐Loken syndrome

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99013/1/cge12196.pd