Mutations of the mitochondrial-tRNA modifier MTO1 cause hypertrophic cardiomyopathy and lactic acidosis

Dysfunction of mitochondrial respiration is an increasingly recognized cause of isolated hypertrophic cardiomyopathy. To gain insight into the genetic origin of this condition, we used next-generation exome sequencing to identify mutations in MTO1, which encodes mitochondrial translation optimization 1. Two affected siblings carried a maternal c.1858dup (p.Arg620Lysfs^∗8) frameshift and a paternal c.1282G>A (p.Ala428Thr) missense mutation. A third unrelated individual was homozygous for the latter change. In both humans and yeast, MTO1 increases the accuracy and efficiency of mtDNA translation by catalyzing the 5-carboxymethylaminomethylation of the wobble uridine base in three mitochondrial tRNAs (mt-tRNAs). Accordingly, mutant muscle and fibroblasts showed variably combined reduction in mtDNA-dependent respiratory chain activities. Reduced respiration in mutant cells was corrected by expressing a wild-type MTO1 cDNA. Conversely, defective respiration of a yeast mto1Δ strain failed to be corrected by an Mto1^Pro622∗ variant, equivalent to human MTO1^{Arg620Lysfs∗8}, whereas incomplete correction was achieved by an Mto1^Ala431Thr variant, corresponding to human MTO1^Ala428Thr. The respiratory yeast phenotype was dramatically worsened in stress conditions and in the presence of a paromomycin-resistant (P^R) mitochondrial rRNA mutation. Lastly, in vivo mtDNA translation was impaired in the mutant yeast strains.     

Isoform identification, recombinant production and characterization of the allergen lipid transfer protein 1 from pear (Pyr c 3)

Non-specific lipid transfer proteins belonging to LTP1 family represent the most important allergens for non pollen-related allergies to Rosaceae fruits in the Mediterranean area. Peach LTP1 (Pru p 3) is a major allergen and is considered the prototypic allergenic LTP. On the contrary, pear allergy without pollinosis seems to be under-reported when compared to other Rosaceae fruits suggesting that the as-yet-uncharacterized pear LTP1 (Pyr c 3) has in vivo a low allergenicity. We report here on the identification of four cDNAs encoding for LTP1 in pear fruits. The two isoforms exhibiting amino acid sequences most similar to those of peach and apple homologues were obtained as recombinant proteins. Such isoforms exhibited CD spectra and lipid binding ability typical of LTP1 family. Moreover, pear LTP1 mRNA was mainly found in the peel, as previously shown for other Rosaceae fruits. By means of IgE ELISA assays a considerable immunoreactivity of these proteins to LTP-sensitive patient sera was detected, even though allergic reactions after ingestion of pear were not reported in the clinical history of the patients. Finally, the abundance of LTP1 in protein extracts from pear peel, in which LTP1 from Rosaceae fruits is mainly confined, was estimated to be much lower as compared to peach peel. Our data suggest that the two isoforms of pear LTP1 characterized in this study possess biochemical features and IgE-binding ability similar to allergenic LTPs. Their low concentrations in pear might be the cause of the low frequency of LTP-mediated pear allergy.     

What model suits ecosystem-based fisheries management? A plea for a structured modeling process

As tools within ecosystem-based fisheries management (EBFM), a wide range of Ecosystem Models (EMs) have been designed to represent ecosystem complexity, but it is not always clear how the outputs of these models can be applied. We address this debate in a literature review to illustrate how a better understanding of ecosystem modeling within the EBFM framework could facilitate the use of EMs in the decision-making process. We classify EMs according to their complexity, and qualitatively evaluate their level of success with regard to five general goals of EBFM. In principle, no single EM is found to successfully accomplish all the EBFM goals. Therefore, we suggest that the way in which ecosystem modeling can effectively contribute to EBFM is through a structured modeling process, which should be pursued according to the context of each specific area. Within this planning strategy a range of Ems should be considered, from rather simple ones with few parameters, whose outputs are scientifically robust but possibly of limited use within the EBFM, to those which include a large number of ecosystem elements yet at the expense of increased uncertainty. If multiple EMs, despite their different assumptions, leads to consistent and converging results then robust management decisions will be supported. The present paper appears particularly useful to anyone confronted with the selection of modeling tools for the implementation of fisheries management strategies considering the particular situation of the fishery.     

Plantlet recruitment is the key demographic transition in invasion by Kalanchoe daigremontiana

Biological invasions have a great impact on biodiversity and ecosystem functioning worldwide. Kalanchoe daigremontiana is a noxious invasive plant in arid zones. Besides being toxic for domestic animals and wildlife, this species inhibits the growth of native plants. Its rapid proliferation in Cerro Saroche National Park (Venezuela) is of great concern because this area hosts several species endemic to the scarce arid zones in the Caribbean. The traits of K. daigremontiana that contribute to its invasive success are unknown. Based on empirical data, we derived a stage structured, stochastic and density-dependent model, to identify characteristics relevant for its establishment. Sensitivity analyses revealed that the establishment of K. daigremontiana depends exclusively on plantlet recruitment. Because asexual plantlets reproduce in less than 1 year populations are able to increase rapidly during the initial phases of invasion, when extinction risks are higher. Sexual seedlings, on the contrary, require a minimum of 3 years to reproduce. As a result, seedling recruitment contributes little to the transient dynamics of the population and therefore cannot warrant the successful establishment of the species. Simulations of various management strategies show that eradication through plant removal may only be achieved if harvest begins shortly after introduction. If a rapid response is not possible, reducing the survival and growth rates of plantlets through biological control is an alternative option. Thus, a strict control of dispersal of plantlets by humans and a continuous monitoring of new invasions should be the first priority for reducing further impact on native species.     

Brain delivery of AAV9 expressing an anti-PrP monovalent antibody delays prion disease in mice

Prion diseases are caused by a conformational modification of the cellular prion protein (PrP^C) into disease-specific forms, termed PrP^Sc, that have the ability to interact with PrP^C promoting its conversion to PrP^Sc. In vitro studies demonstrated that anti-PrP antibodies inhibit this process. In particular, the single chain variable fragment D18 antibody (scFvD18) showed high efficiency in curing chronically prion-infected cells. This molecule binds the PrP^C region involved in the interaction with PrP^Sc thus halting further prion formation. These findings prompted us to test the efficiency of scFvD18 in vivo. A recombinant Adeno-Associated Viral vector serotype 9 was used to deliver scFvD18 to the brain of mice that were subsequently infected by intraperitoneal route with the mouse-adapted scrapie strain RML. We found that the treatment was safe, prolonged the incubation time of scrapie-infected animals and decreased the burden of total proteinase-resistant PrP^Sc in the brain, suggesting that scFvD18 interferes with prion replication in vivo. This approach is relevant for designing new therapeutic strategies for prion diseases and other disorders characterized by protein misfolding.     

NMR study of the selective inhibition of water permeability of rat erythrocyte membrane

The inhibition of water diffusion across the rat erythrocyte membrane was studied by NMR using two basically different types of inhibitory agents: PCMB andin vivo irradiation. The contribution of lipid and protein to water permeability revealed the inhibitory effect of each pathway. Internal contamination with tritium (25–115 mGy) reduces water permeability due to protein modifications; for doses higher than 100 mGy the lipid mediated mechanism seems also to be impaired. The same procedure enables one to assess the extent to which the higher water permeability of rat, compared to human, erythrocyte is due to one of the two pathways.     

Selective enzymatic hydrolysis of aromatic diesters using esterase from Brevibacterium imperiale B222

Summary A practical procedure has been developed for the chemoselective microbial hydrolysis of aromatic dicarboxylic esters to give the corresponding monoesters, using cellular lysate and whole cell of Brevibacterium imperiale B222. The produced monoesters can be transformed into hydroxyacids, useful intermediates in the synthesis of polyesters.     

Bioavailability and dosing strategies of mineral in anaerobic mono‐digestion of maize straw

The influence of the bonding form distribution of Fe, Ni, Co and Mn and their potential bioavailability during the anaerobic degradation of maize straw was investigated. Two reactors were operated over 117 days at 37°C and different dosage strategies of mineral were studied in reactor (R2). Control reactor (R1) was metal‐limited over time. mineral supplementation (1 g L^?1) once a week reported the highest methane yield (257 mL g^?1 VS) with 30% of increment. Ni and Co predominated in their oxidizable bonding forms and Fe mainly existed as residual and oxidizable fractions. The potential bioavailability (Mn ?? Co ≈ Ni ? Fe) of R2 was higher comparing to R1. Metal deprivation in R1 led to depletion of both sequential extraction fractions and total metal concentrations until the end of the process. This study confirmed that the dosage strategy of mineral has a stimulatory effect on methane production from crop maize waste.     

Initiating Events in Direct Cardiomyocyte Reprogramming

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