Fractional differentiability for solutions of nonlinear elliptic equations

We study nonlinear elliptic equations in divergence form $${\operatorname{div}}{\mathcal A}(x,Du)={\operatorname{div}}G.$$ When ${\mathcal A}$ has linear growth in $Du$, and assuming that $x\mapsto{\mathcal A}(x,\xi)$ enjoys $B^\alpha_{\frac{n}\alpha, q}$ smoothness, local well-posedness is found in $B^\alpha_{p,q}$ for certain values of $p\in[2,\frac{n}{\alpha})$ and $q\in[1,\infty]$. In the particular case ${\mathcal A}(x,\xi)=A(x)\xi$, $G=0$ and $A\in B^\alpha_{\frac{n}\alpha,q}$, $1\leq q\leq\infty$, we obtain $Du\in B^\alpha_{p,q}$ for each $p<\frac{n}\alpha$. Our main tool in the proof is a more general result, that holds also if ${\mathcal A}$ has growth $s-1$ in $Du$, $2\leq s\leq n$, and asserts local well-posedness in $L^q$ for each $q>s$, provided that $x\mapsto{\mathcal A}(x,\xi)$ satisfies a locally uniform $VMO$ condition

A RNA-Seq Analysis to Describe the Boar Sperm Transcriptome and Its Seasonal Changes

Understanding the molecular basis of cell function and ultimate phenotypes is crucial for the development of biological markers. With this aim, several RNA-seq studies have been devoted to the characterization of the transcriptome of ejaculated spermatozoa in relation to sperm quality and fertility. Semen quality follows a seasonal pattern and decays in the summer months in several animal species. The aim of this study was to deeply profile the transcriptome of the boar sperm and to evaluate its seasonal changes. We sequenced the total and the short fractions of the sperm RNA from 10 Pietrain boars, 5 collected in summer and 5 five sampled in winter, and identified a complex and rich transcriptome with 4,436 coding genes of moderate to high abundance. Transcript fragmentation was high but less obvious in genes related to spermatogenesis, chromatin compaction and fertility. Short non-coding RNAs mostly included piwi-interacting RNAs, transfer RNAs and microRNAs. We also compared the transcriptome of the summer and the winter ejaculates and identified 34 coding genes and 7 microRNAs with a significantly distinct distribution. These genes were mostly related to oxidative stress, DNA damage and autophagy. This is the deepest characterization of the boar sperm transcriptome and the first study linking the transcriptome and the seasonal variability of semen quality in animals. The annotation described here can be used as a reference for the identification of markers of sperm quality in pigs

Impact of two myostatin (MSTN) mutations on weight gain and lamb carcass classification in Norwegian White Sheep (Ovis aries)

<p>Abstract</p> <p>Background</p> <p>Our aim was to estimate the effect of two <it>myostatin </it>(<it>MSTN</it>) mutations in Norwegian White Sheep, one of which is close to fixation in the Texel breed.</p> <p>Methods</p> <p>The impact of two known <it>MSTN </it>mutations was examined in a field experiment with Norwegian White Sheep. The joint effect of the two <it>MSTN </it>mutations on live weight gain and weaning weight was studied on 644 lambs. Carcass weight gain from birth to slaughter, carcass weight, carcass conformation and carcass fat classes were calculated in a subset of 508 lambs. All analyses were carried out with a univariate linear animal model.</p> <p>Results</p> <p>The most significant impact of both mutations was on conformation and fat classes. The largest difference between the genotype groups was between the wild type for both mutations and the homozygotes for the c.960delG mutation. Compared to the wild types, these mutants obtained a conformation score 5.1 classes higher and a fat score 3.0 classes lower, both on a 15-point scale.</p> <p>Conclusions</p> <p>Both mutations reduced fatness and increased muscle mass, although the effect of the frameshift mutation (c.960delG) was more important as compared to the 3'-UTR mutation (c.2360G>A). Lambs homozygous for the c.960delG mutation grew more slowly than those with other <it>MSTN </it>genotypes, but had the least fat and the largest muscle mass. Only c.960delG showed dominance effects.</p

A systems model for immune cell interactions unravels the mechanism of inflammation in human skin

Inflammation is characterized by altered cytokine levels produced by cell populations in a highly interdependent manner. To elucidate the mechanism of an inflammatory reaction, we have developed a mathematical model for immune cell interactions via the specific, dose-dependent cytokine production rates of cell populations. The model describes the criteria required for normal and pathological immune system responses and suggests that alterations in the cytokine production rates can lead to various stable levels which manifest themselves in different disease phenotypes. The model predicts that pairs of interacting immune cell populations can maintain homeostatic and elevated extracellular cytokine concentration levels, enabling them to operate as an immune system switch. The concept described here is developed in the context of psoriasis, an immune-mediated disease, but it can also offer mechanistic insights into other inflammatory pathologies as it explains how interactions between immune cell populations can lead to disease phenotypes. © 2010 Valeyev et al

Two novel missense mutations in the myostatin gene identified in Japanese patients with Duchenne muscular dystrophy

BACKGROUND: Myostatin is a negative regulator of skeletal muscle growth. Truncating mutations in the myostatin gene have been reported to result in gross muscle hypertrophy. Duchenne muscular dystrophy (DMD), the most common lethal muscle wasting disease, is a result of an absence of muscle dystrophin. Although this disorder causes a rather uniform pattern of muscle wasting, afflicted patients display phenotypic variability. We hypothesized that genetic variation in myostatin is a modifier of the DMD phenotype. METHODS: We analyzed 102 Japanese DMD patients for mutations in the myostatin gene. RESULTS: Two polymorphisms that are commonly observed in Western countries, p.55A>T and p.153K>R, were not observed in these Japanese patients. An uncommon polymorphism of p.164E>K was uncovered in four cases; each patient was found to be heterozygous for this polymorphism, which had the highest frequency of the polymorphism observed in the Japanese patients. Remarkably, two patients were found to be heterozygous for one of two novel missense mutations (p.95D>H and p.156L>I). One DMD patient carrying a novel missense mutation of p.95D>H was not phenotypically different from the non-carriers. The other DMD patient was found to carry both a novel mutation (p.156L>I) and a known polymorphism (p.164E>K) in one allele, although his phenotype was not significantly modified. Any nucleotide change creating a target site for micro RNAs was not disclosed in the 3' untranslated region. CONCLUSION: Our results indicate that heterozygous missense mutations including two novel mutations did not produce an apparent increase in muscle strength in Japanese DMD cases, even in a patient carrying two missense mutations

Quadrupling Muscle Mass in Mice by Targeting TGF-ß Signaling Pathways

Myostatin is a transforming growth factor-ß family member that normally acts to limit skeletal muscle growth. Mice genetically engineered to lack myostatin activity have about twice the amount of muscle mass throughout the body, and similar effects are seen in cattle, sheep, dogs, and a human with naturally occurring loss-of-function mutations in the myostatin gene. Hence, there is considerable interest in developing agents capable of inhibiting myostatin activity for both agricultural and human therapeutic applications. We previously showed that the myostatin binding protein, follistatin, can induce dramatic increases in muscle mass when overexpressed as a transgene in mice. In order to determine whether this effect of follistatin results solely from inhibition of myostatin activity, I analyzed the effect of this transgene in myostatin-null mice. Mstn−/− mice carrying a follistatin transgene had about four times the muscle mass of wild type mice, demonstrating the existence of other regulators of muscle mass with similar activity to myostatin. The greatest effect on muscle mass was observed in offspring of mothers homozygous for the Mstn mutation, raising the possibility that either myostatin itself or a downstream regulator may normally be transferred from the maternal to fetal circulations. These findings demonstrate that the capacity for increasing muscle growth by manipulating TGF-ß signaling pathways is much more extensive than previously appreciated and suggest that muscle mass may be controlled at least in part by a systemic mode of action of myostatin

A possible role for miRNA silencing in disease phenotype variation in Swedish transthyretin V30M carriers

Our results are the first to show the presence of a 3'UTR polymorphism on the V30M haplotype in Swedish carriers, which can serve as a miRNA binding site potentially leading to down-regulated expression from the mutated TTR allele. This finding may be related to the low penetrance and high age at onset of the disease observed in the Swedish patient population