Biallelic P4HTM variants associated with HIDEA syndrome and mitochondrial respiratory chain complex I deficiency

We report a patient with profound congenital hypotonia, central hypoventilation, poor visual behaviour with retinal hypopigmentation, and significantly decreased mitochondrial respiratory chain complex I activity in muscle, who died at 7 months of age having made minimal developmental progress. Biallelic predicted truncating P4HTM variants were identified following trio whole-genome sequencing, consistent with a diagnosis of hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy and eye abnormalities (HIDEA) syndrome. Very few patients with HIDEA syndrome have been reported previously and mitochondrial abnormalities were observed in three of four previous cases who had a muscle biopsy, suggesting the possibility that HIDEA syndrome represents a primary mitochondrial disorder. P4HTM encodes a transmembrane prolyl 4-hydroxylase with putative targets including hypoxia inducible factors, RNA polymerase II and activating transcription factor 4, which has been implicated in the integrated stress response observed in cell and animal models of mitochondrial disease, and may explain the mitochondrial dysfunction observed in HIDEA syndrome

Non-communicable diseases in the Western Area District, Sierra Leone, before and during the Ebola outbreak.

Setting: Twenty-seven peripheral health units, five secondary hospitals and one tertiary hospital, Western Area District, Sierra Leone. Objectives: To describe reporting systems, monthly attendances and facility-based patterns of six non-communicable diseases (NCDs) in the pre-Ebola and Ebola virus disease outbreak periods. Design: A cross-sectional study using programme data. Results: Reporting was 89% complete on the six selected NCDs pre-Ebola and 86% during the Ebola outbreak (P < 0.01). Overall, marked declining trends in NCDs were reported during the Ebola period, with a monthly mean of 342 cases pre-Ebola and 164 during the Ebola outbreak. The monthly mean number of cases per disease in the pre-Ebola and Ebola outbreak periods was respectively 228 vs. 85 for hypertension, 43 vs. 27 for cardiovascular diseases, 36 vs. 18 for diabetes and 25 vs. 29 for peptic ulcer disease; this last condition increased during the outbreak. There were higher proportions of NCDs among females during the Ebola outbreak compared with the pre-Ebola period. Except for peptic ulcer disease, the number of patients with NCDs declined by 25% in peripheral health units, 91% in the secondary hospitals and 70% in the tertiary hospital between the pre-Ebola and the Ebola outbreak periods. Conclusion: Comprehensive reporting of NCDs was suboptimal, and declined during the Ebola epidemic. There were decreases in reported attendances for NCDs between the pre-Ebola and the Ebola outbreak periods, which were even more marked in the hospitals. This study has important policy implications

What Brown saw and you can too

A discussion is given of Robert Brown's original observations of particles ejected by pollen of the plant \textit{Clarkia pulchella} undergoing what is now called Brownian motion. We consider the nature of those particles, and how he misinterpreted the Airy disc of the smallest particles to be universal organic building blocks. Relevant qualitative and quantitative investigations with a modern microscope and with a "homemade" single lens microscope similar to Brown's, are presented.Comment: 14.1 pages, 11 figures, to be published in the American Journal of Physics. This differs from the previous version only in the web site referred to in reference 3. Today, this Brownian motion web site was launched, and http://physerver.hamilton.edu/Research/Brownian/index.html, is now correc

Finite temperature molecular dynamics study of unstable stacking fault free energies in silicon

We calculate the free energies of unstable stacking fault (USF) configurations on the glide and shuffle slip planes in silicon as a function of temperature, using the recently developed Environment Dependent Interatomic Potential (EDIP). We employ the molecular dynamics (MD) adiabatic switching method with appropriate periodic boundary conditions and restrictions to atomic motion that guarantee stability and include volume relaxation of the USF configurations perpendicular to the slip plane. Our MD results using the EDIP model agree fairly well with earlier first-principles estimates for the transition from shuffle to glide plane dominance as a function of temperature. We use these results to make contact to brittle-ductile transition models.Comment: 6 pages revtex, 4 figs, 16 refs, to appear in Phys. Rev.

On waiting for something to happen

This paper seeks to examine two particular and peculiar practices in which the mediation of apparently direct encounters is made explicit and is systematically theorized: that of the psychoanalytic dialogue with its inward focus and private secluded setting, and that of theatre and live performance, with its public focus. Both these practices are concerned with ways in which “live encounters” impact on their participants, and hence with the conditions under which, and the processes whereby, the coming-together of human subjects results in recognizable personal or social change. Through the rudimentary analysis of two anecdotes, we aim to think these encounters together in a way that explores what each borrows from the other, the psychoanalytic in the theatrical, the theatrical in the psychoanalytic, figuring each practice as differently committed to what we call the “publication of liveness”. We argue that these “redundant” forms of human contact continue to provide respite from group acceptance of narcissistic failure in the post-democratic era through their offer of a practice of waiting

Global human frequencies of predicted nuclear pathogenic variants and the role played by protein hydrophobicity in pathogenicity potential

Mitochondrial proteins are coded by nuclear (nDNA) and mitochondrial (mtDNA) genes, implying a complex cross-talk between the two genomes. Here we investigated the diversity displayed in 104 nuclear-coded mitochondrial proteins from 1,092 individuals from the 1000 Genomes dataset, in order to evaluate if these genes are under the effects of purifying selection and how that selection compares with their mitochondrial encoded counterparts. Only the very rare variants (frequency < 0.1%) in these nDNA genes are indistinguishable from a random set from all possible variants in terms of predicted pathogenicity score, but more frequent variants display distinct signs of purifying selection. Comparisons of selection strength indicate stronger selection in the mtDNA genes compared to this set of nDNA genes, accounted for by the high hydrophobicity of the proteins coded by the mtDNA. Most of the predicted pathogenic variants in the nDNA genes were restricted to a single continental population. The proportion of individuals having at least one potential pathogenic mutation in this gene set was significantly lower in Europeans than in Africans and Asians. This difference may reflect demographic asymmetries, since African and Asian populations experienced main expansions in middle Holocene, while in Europeans the main expansions occurred earlier in the post-glacial period

Digestion of Starch Granules from Maize, Potato and Wheat by Larvae of the the Yellow Mealworm, Tenebrio molitor and the Mexican Bean Weevil, Zabrotes subfasciatus

Scanning electron microscopy images were taken of starch granules from different sources following exposure in vivo and in vitro to gut α-amylases isolated from Tenebrio molitor L. (Coleoptera: Tenebrionidae) and Zabrotes subfasciatus Boheman (Coleoptera: Bruchidae). One α-amylase was isolated from whole larval midguts of T. molitor using non-denaturing SDS-PAGE, while two other α-amylase fractions were isolated from whole larval midguts of Z. subfasciatus using hydrophobic interaction chromatography., Digested starch granules from larvae fed on maize, potato or wheat were isolated from midgut contents. Combinations of starch granules with isolated α-amylases from both species showed similar patterns of granule degradation. In vitro enzymatic degradation of maize starch granules by the three different α-amylase fractions began by creating small holes and crater-like areas on the surface of the granules. Over time, these holes increased in number and area resulting in extensive degradation of the granule structure. Granules from potato did not show formation of pits and craters on their surface, but presented extensive erosion in their interior. For all types of starch, as soon as the interior of the starch granule was reached, the inner layers of amylose and amylopectin were differentially hydrolyzed, resulting in a striated pattern. These data support the hypothesis that the pattern of starch degradation depends more on the granule type than on the α-amylase involved

Biological Control Production and Germination of Conidia of Trichoderma stromaticum, a Mycoparasite of Crinipellis perniciosa on Cacao

Growth characteristics of the fungus Trichoderma stromaticum, a mycoparasite on the mycelium and fruiting bodies of Crinipellis perniciosa, the causal agent of witches&apos;-broom disease of cacao, were evaluated under controlled environmental conditions. The ability of T. stromaticum to produce conidia and germinate on dry brooms was evaluated at three constant temperatures (20, 25, and 30°C) and two constant relative humidities (75 and 100%). T. stromaticum produced abundant conidia on brooms at 100% relative humidity and incubation temperatures of 20 and 25°C, but none at 30°C. Sporulation of T. stromaticum was not observed at 75% relative humidity at any temperature. At 100% relative humidity and either at 20 or 25°C, treatment of brooms with T. stromaticum suppressed C. perniciosa within 7 days. In contrast, at 30°C, treatment with T. stromaticum had no effect on the pathogen in brooms maintained at either 75 or 100% relative humidity. Mycelium of C. perniciosa grew from brooms at all temperatures at 100% relative humidity. Conidial germination on broom tissue approximated 80% at temperatures from 20 to 30°C. Results suggest that applying T. stromaticum under high-moisture conditions when the air temperature is below 30°C may enhance the establishment of this mycoparasite in cacao plantations. Additional keyword: Theobroma cacao