Sweet taste loss in myasthenia gravis: more than a coincidence?

Sweet dysgeusia, a rare taste disorder, may be encountered in severe anti-acetylcholine receptor antibody (AChRAb)-myasthenia gravis (MG). A 42 year-old man reported progressive loss of sweet taste evolving for almost 10 weeks, revealing an AChRAb-positive MG with thymoma. Improvement of sweet perception paralleled reduction of the MG composite score during the 15 months follow up period, with immunosuppressive and surgical treatments. We suggest that sweet dysgeusia is a non-motor manifestation of MG that may result from a thymoma-dependent autoimmune mechanism targeting gustducin-positive G-protein-coupled taste receptor cells, in line with recent data from MRL/MpJ-Fas lpr/ (MRL/lpr) transgenic mice with autoimmune disease.

Loss-of-function mutations of an inhibitory upstream ORF in the human hairless transcript cause Marie Unna hereditary hypotrichosis.

Marie Unna hereditary hypotrichosis (MUHH) is an autosomal dominant form of genetic hair loss. In a large Chinese family carrying MUHH, we identified a pathogenic initiation codon mutation in U2HR, an inhibitory upstream ORF in the 5' UTR of the gene encoding the human hairless homolog (HR). U2HR is predicted to encode a 34-amino acid peptide that is highly conserved among mammals. In 18 more families from different ancestral groups, we identified a range of defects in U2HR, including loss of initiation, delayed termination codon and nonsense and missense mutations. Functional analysis showed that these classes of mutations all resulted in increased translation of the main HR physiological ORF. Our results establish the link between MUHH and U2HR, show that fine-tuning of HR protein levels is important in control of hair growth, and identify a potential mechanism for preventing hair loss or promoting hair removal.

Transformation kernel density estimation of actuarial loss functions

[cat] Es presenta un estimador nucli transformat que és adequat per a distribucions de cua pesada. Utilitzant una transformació basada en la distribució de probabilitat Beta l’elecció del paràmetre de finestra és molt directa. Es presenta una aplicació a dades d’assegurances i es mostra com calcular el Valor en Risc.

Ruin Theory with Excess of Loss Reinsurance and Reinstatements

The present paper studies the probability of ruin of an insurer, if excess of loss reinsurance with reinstatements is applied. In the setting of the classical Cramer-Lundberg risk model, piecewise deterministic Markov processes are used to describe the free surplus process in this more general situation. It is shown that the finite-time ruin probability is both the solution of a partial integro-differential equation and the fixed point of a contractive integral operator. We exploit the latter representation to develop and implement a recursive algorithm for numerical approximation of the ruin probability that involves high-dimensional integration. Furthermore we study the behavior of the finite-time ruin probability under various levels of initial surplus and security loadings and compare the efficiency of the numerical algorithm with the computational alternative of stochastic simulation of the risk process. (C) 2011 Elsevier Inc. All rights reserved.

Loss of the thyroid hormone-binding protein Crym renders striatal neurons more vulnerable to mutant huntingtin in Huntington's disease.

The mechanisms underlying preferential atrophy of the striatum in Huntington's disease (HD) are unknown. One hypothesis is that a set of gene products preferentially expressed in the striatum could determine the particular vulnerability of this brain region to mutant huntingtin (mHtt). Here, we studied the striatal protein µ-crystallin (Crym). Crym is the NADPH-dependent p38 cytosolic T3-binding protein (p38CTBP), a key regulator of thyroid hormone (TH) T3 (3,5,3'-triiodo-l-thyronine) transportation. It has been also recently identified as the enzyme that reduces the sulfur-containing cyclic ketimines, which are potential neurotransmitters. Here, we confirm the preferential expression of the Crym protein in the rodent and macaque striatum. Crym expression was found to be higher in the macaque caudate than in the putamen. Expression of Crym was reduced in the BACHD and Knock-in 140CAG mouse models of HD before onset of striatal atrophy. We show that overexpression of Crym in striatal medium-size spiny neurons using a lentiviral-based strategy in mice is neuroprotective against the neurotoxicity of an N-terminal fragment of mHtt in vivo. Thus, reduction of Crym expression in HD could render striatal neurons more susceptible to mHtt suggesting that Crym may be a key determinant of the vulnerability of the striatum. In addition our work points to Crym as a potential molecular link between striatal degeneration and the THs deregulation reported in HD patients.

Joint evolution of dispersal and inbreeding load.

Inbreeding avoidance is often invoked to explain observed patterns of dispersal, and theoretical models indeed point to a possibly important role. However, while inbreeding load is usually assumed constant in these models, it is actually bound to vary dynamically under the combined influences of mutation, drift, and selection and thus to evolve jointly with dispersal. Here we report the results of individual-based stochastic simulations allowing such a joint evolution. We show that strongly deleterious mutations should play no significant role, owing to the low genomic mutation rate for such mutations. Mildly deleterious mutations, by contrast, may create enough heterosis to affect the evolution of dispersal as an inbreeding-avoidance mechanism, but only provided that they are also strongly recessive. If slightly recessive, they will spread among demes and accumulate at the metapopulation level, thus contributing to mutational load, but not to heterosis. The resulting loss of viability may then combine with demographic stochasticity to promote population fluctuations, which foster indirect incentives for dispersal. Our simulations suggest that, under biologically realistic parameter values, deleterious mutations have a limited impact on the evolution of dispersal, which on average exceeds by only one-third the values expected from kin-competition avoidance.

Behavioral avoidance tests to evaluate effects of cattle slurry and dairy sludge application to soil¹

The application of organic wastes to agricultural soils is not risk-free and can affect soil invertebrates. Ecotoxicological tests based on the behavioral avoidance of earthworms and springtails were performed to evaluate effects of different fertilization strategies on soil quality and habitat function for soil organisms. These tests were performed in soils treated with: i) slurry and chemical fertilizers, according to the conventional fertilization management of the region, ii) conventional fertilization + sludge and iii) unfertilized reference soil. Both fertilization strategies contributed to soil acidity mitigation and caused no increase in soil heavy metal content. Avoidance test results showed no negative effects of these strategies on soil organisms, compared with the reference soil. However, results of the two fertilization managements differed: Springtails did not avoid soils fertilized with dairy sludge in any of the tested combinations. Earthworms avoided soils treated with sludge as of May 2004 (DS1), when compared with conventional fertilization. Possibly, the behavioral avoidance of earthworms is more sensitive to soil properties (other than texture, organic matter and heavy metal content) than springtails

A Heterozygous Deletion Mutation in the Cardiac Sodium Channel Gene SCN5A with Loss- and Gain-of-Function Characteristics Manifests as Isolated Conduction Disease, without Signs of Brugada or Long QT Syndrome.

BACKGROUND: The SCN5A gene encodes for the α-subunit of the cardiac sodium channel NaV1.5, which is responsible for the rapid upstroke of the cardiac action potential. Mutations in this gene may lead to multiple life-threatening disorders of cardiac rhythm or are linked to structural cardiac defects. Here, we characterized a large family with a mutation in SCN5A presenting with an atrioventricular conduction disease and absence of Brugada syndrome. METHOD AND RESULTS: In a large family with a high incidence of sudden cardiac deaths, a heterozygous SCN5A mutation (p.1493delK) with an autosomal dominant inheritance has been identified. Mutation carriers were devoid of any cardiac structural changes. Typical ECG findings were an increased P-wave duration, an AV-block I° and a prolonged QRS duration with an intraventricular conduction delay and no signs for Brugada syndrome. HEK293 cells transfected with 1493delK showed strongly (5-fold) reduced Na(+) currents with altered inactivation kinetics compared to wild-type channels. Immunocytochemical staining demonstrated strongly decreased expression of SCN5A 1493delK in the sarcolemma consistent with an intracellular trafficking defect and thereby a loss-of-function. In addition, SCN5A 1493delK channels that reached cell membrane showed gain-of-function aspects (slowing of the fast inactivation, reduction in the relative fraction of channels that fast inactivate, hastening of the recovery from inactivation). CONCLUSION: In a large family, congregation of a heterozygous SCN5A gene mutation (p.1493delK) predisposes for conduction slowing without evidence for Brugada syndrome due to a predominantly trafficking defect that reduces Na(+) current and depolarization force.

Relationship of breast fillet deboning time to shear force, pH, cooking loss and color in broilers stunned by high electrical current

Selostus: Korkealla virranvoimakkuudella tainnutettujen broilereiden rintafileen irroitushetken vaikutus lihaksen leikkausvoiman vastukseen, pH:hon, keittohävikkiin ja väriin

Intensity correlation functions of dye lasers: Comparison of colored-gain-noise and colored-loss-noise models

The intensity correlation functions C(t) for the colored-gain-noise model of dye lasers are analyzed and compared with those for the loss-noise model. For correlation times ¿ larger than the deterministic relaxation time td, we show with the use of the adiabatic approximation that C(t) values coincide for both models. For small correlation times we use a method that provides explicit expressions of non-Markovian correlation functions, approximating simultaneously short- and long-time behaviors. Comparison with numerical simulations shows excellent results simultaneously for short- and long-time regimes. It is found that, when the correlation time of the noise increases, differences between the gain- and loss-noise models tend to disappear. The decay of C(t) for both models can be described by a time scale that approaches the deterministic relaxation time. However, in contrast with the loss-noise model, a secondary time scale remains for large times for the gain-noise model, which could allow one to distinguish between both models.

Loss of ammonia from nitrogen fertilizers applied to maize and soybean straw

In Brazilian agriculture, urea is the most commonly used nitrogen (N) source, in spite of having the disadvantage of losing considerable amounts of N by ammonia-N volatilization. The objectives of this study were to evaluate: N lossby ammonia volatilization from: [urea coated with copper sulfate and boric acid], [urea coated with zeolite], [urea+ammonium sulfate], [urea coated with copper sulfate and boric acid+ammonium sulfate], [common urea] and [ammonium nitrate]; and the effect of these N source son the maize yield in terms of amount and quality. The treatments were applied to the surface of a soil under no-tillage maize, in two growing seasons. The first season (2009/2010) was after a maize crop (maize straw left on the soil surface) and the second cycle (2012/2011) after a soybean crop. Due to the weather conditions during the experiments, the volatilization of ammonia-N was highest in the first four days after application of the N sources. Of all urea sources, under volatilization-favorable conditions, the loss of ammonia from urea coated with copper sulfate and boric acid was lowest, while under high rainfall, the losses from the different urea sources was similar, i.e., an adequate rainfall was favorablet o reduce volatilization. The ammonia volatilization losses were greatest in the first four days after application. Maize grain yield differed due to N application and in the treatments, but this was only observed with cultivation of maize crop residues in 2009/2010. The combination of ammonium+urea coated with copper sulfate and boric acid optimized grain yield compared to the other urea treatments. The crude protein concentration in maize was not influenced by the technologies of urea coating.

Interventions aiming at balance confidence improvement in older adults: an updated review.

BACKGROUND: Loss of balance confidence is a frequent condition that affects 20-75% of community-dwelling older persons. Although a recent fall is a common trigger, loss of balance confidence also appears independent of previous experience with falls. Maintaining or improving balance confidence is important to avoid unnecessary, self-imposed restrictions of activity and subsequent disability. Holding another person's hand or using an assistive device while walking are simple interventions that are used naturally to address poor balance confidence in daily life. However, more complex interventions have also been developed and tested to achieve more sustained improvement in balance confidence. OBJECTIVES: This review describes interventions that have been tested to improve balance confidence in older community-dwelling persons. METHODS: Based on 2 recent systematic reviews, an additional search for literature was performed to update current information on interventions aiming at balance confidence improvement. Interventions were classified as those directly aimed at increasing balance confidence or not, and further stratified into those using monofactorial or multifactorial approaches. RESULTS: A total of 46 randomized controlled trials were identified. Five of the 8 interventions that directly targeted balance confidence showed benefits. Among those, multicomponent behavioral group interventions provided the most robust evidence of benefits in improving balance confidence and in decreasing activity avoidance. Among interventions not directly aiming at balance confidence improvement (11/21 studies with benefits), exercise (including tai chi) appears as the most promising monofactorial intervention. Nine of the 17 multifactorial fall prevention programs showed an effect on balance confidence, exercise being a main component in 7 of these 9 studies. Interventions that targeted elderly persons reporting poor balance confidence and/or those at risk for falls seemed more likely to be beneficial. CONCLUSIONS: Positive and sometimes sustained improvement in balance confidence can be achieved by various interventions among community-dwelling elderly persons. The effect of these interventions on activity restriction associated with poor balance confidence have been less well studied, but some studies also suggest potential benefits.