Mutations in protein N-arginine methyltransferases are not the cause of FTLD-FUS

The nuclear protein fused in sarcoma (FUS) is found in cytoplasmic inclusions in a subset of patients with the neurodegenerative disorder frontotemporal lobar degeneration (FTLD-FUS). FUS contains a methylated arginine–glycine–glycine domain that is required for transport into the nucleus. Recent findings have shown that this domain is hypomethylated in patients with FTLD-FUS. To determine whether the cause of hypomethylation is the result of mutations in protein N-arginine methyltransferases (PRMTs), we selected 3 candidate genes (PRMT1, PRMT3, and PRMT8) and performed complete sequencing analysis and real-time polymerase chain reaction mRNA expression analysis in 20 FTLD-FUS cases. No mutations or statistically significant changes in expression were observed in our patient samples, suggesting that defects in PRMTs are not the cause of FTLD-FUS.     

Beyond physiotherapy and pharmacological treatment for fibromyalgia syndrome: tailored tACS as a new therapeutic tool

European Archives of Psychiatry and Clinical Neuroscience - Fibromyalgia syndrome (FMS) is a complex pain disorder, characterized by diffuse pain and cognitive disturbances. Abnormal cortical...     

Influence of a metaphylactic treatment with Baycox® Bovis on the reproductive performances of Fresian heifers: a preliminary study

A blind, randomised, controlled, multicentric field trial was conducted to assess the influence of a metaphylactic treatment with an oral solution of toltrazuril on some reproductive parameters of Italian Fresian heifers during the first 18–20 months of life. For this goal 40 calves were selected from two dairy farms and randomly divided into two homogeneous groups: MTol, treated with toltrazuril and NegC, left untreated. The calves were clinically and coprologically examined over the entire study period. The body condition scores, the body weights and the age at the first service were recorded and compared between the two groups, in addition to some other reproductive parameters including number of pregnancies, average service per pregnancy, conception rate, conception rate at first service and post first service conception rate. The analysis of the results showed that the metaphylactic treatment with toltrazuril influenced positively the average age of the first service (MTol 461.4 days versus NegC 485.45 days), the overall conception rate (MTol 95 % versus NegC 85 %), the success at first (MTol 60 % versus NegC 45 %) and second (MTol 75 % versus NegC 45 %) services and, consequently, the mean number of services to be carried out for each animal (MTol 1.4?±?0.6 versus NegC 1.6?±?0.79). Furthermore, the results confirmed that toltrazuril treatment, applied in accordance with the epidemiological aspects of each farm, is highly efficacious in persistent reduction of oocyst excretions with particular reference to Eimeria zuernii, Eimeria bovis, considered to be mainly responsible for clinical coccidiosis.     

Joint action as a practice of memory transmission in a poor urban neighborhood of Santiago,Chile

In Latin America, one of the key tasks of Community and Liberation Psychology has been to recover the memories of marginalized and excluded communities that have experienced multiple pasts marked by political violence. In Chile, researchers have focused on poor urban neighborhoods, where the question of how memories are transmitted in areas where conflicts and violence are still present has been overlooked. In this context, the following article aims to analyze the ways in which memories are transmitted in a neighborhood that has a long organizational history in the struggle against social inequalities; while at the same time being classified as a critical area by the state due to its current levels of violence and social conflict. The researchers led a 3‐year case study from an ethnographic perspective, and applied a collaborative methodology that brought together the research team and the members of a territorial organization. The analysis is based on 72 interviews, 5 conversation groups and ethnographic observation. The data was analyzed using discourse analysis. The results revealed that the main form of memory transmission is not based on intergenerational narratives of the past, but rather on joint action; namely, dialogical practices among neighborhood residents that generate an ethos; a common way of life.     

Evolution and diversity of copy number variation in the great ape lineage

Copy number variation (CNV) contributes to disease and has restructured the genomes of great apes. The diversity and rate of this process, however, have not been extensively explored among great ape lineages. We analyzed 97 deeply sequenced great ape and human genomes and estimate 16% (469 Mb) of the hominid genome has been affected by recent CNV. We identify a comprehensive set of fixed gene deletions (n = 340) and duplications (n = 405) as well as >13.5 Mb of sequence that has been specifically lost on the human lineage. We compared the diversity and rates of copy number and single nucleotide variation across the hominid phylogeny. We find that CNV diversity partially correlates with single nucleotide diversity (r² = 0.5) and recapitulates the phylogeny of apes with few exceptions. Duplications significantly outpace deletions (2.8-fold). The load of segregating duplications remains significantly higher in bonobos, Western chimpanzees, and Sumatran orangutans—populations that have experienced recent genetic bottlenecks (P = 0.0014, 0.02, and 0.0088, respectively). The rate of fixed deletion has been more clocklike with the exception of the chimpanzee lineage, where we observe a twofold increase in the chimpanzee–bonobo ancestor (P = 4.79 × 10⁻⁹) and increased deletion load among Western chimpanzees (P = 0.002). The latter includes the first genomic disorder in a chimpanzee with features resembling Smith-Magenis syndrome mediated by a chimpanzee-specific increase in segmental duplication complexity. We hypothesize that demographic effects, such as bottlenecks, have contributed to larger and more gene-rich segments being deleted in the chimpanzee lineage and that this effect, more generally, may account for episodic bursts in CNV during hominid evolution.Sequence and assembly of great ape reference genomes have consistently revealed that copy number variation (CNV) affects more base pairs than single nucleotide variation (SNV) (Cheng et al. 2005; The Chimpanzee Sequencing and Analysis Consortium 2005; Locke et al. 2011). Segmental duplications, in particular, have disproportionately affected the African great ape (human, chimpanzee, and gorilla) lineages, where they appear to have accumulated at an accelerated rate (Cheng et al. 2005; Marques-Bonet et al. 2009). This has led to speculation that differences in fixation and copy number polymorphism may have contributed to the phenotypic “plasticity” and species-specific differences between humans and great apes (Olson 1999; Varki et al. 2008). While there is some evidence that fixed deletions and duplications contribute to morphological differences between humans and great apes (McLean et al. 2011; Charrier et al. 2012; Dennis et al. 2012), a comprehensive assessment of these differences at the level of the genome has not yet been performed. Previous studies of CNV have been predominated by array comparative genomic hybridization (CGH) experiments (Fortna et al. 2004; Perry et al. 2006; Dumas et al. 2007; Gazave et al. 2011; Locke et al. 2011), which provide limited size resolution, are imprecise in absolute copy number differences, and are biased by probes derived from the human reference genome. Comparisons of reference genomes have been complicated by assessments of a single individual and distinguishing CNVs from assembly errors (The Chimpanzee Sequencing and Analysis Consortium 2005; Locke et al. 2011; Ventura et al. 2011; Prüfer et al. 2012). Here, we compare the evolution and diversity of deletions, duplications, and SNVs in 97 great ape individuals sequenced to high coverage (median ∼25×) (Prado-Martinez et al. 2013). The set includes multiple individuals from the four great ape genera, including Bornean and Sumatran orangutans, each of the four recognized chimpanzee subspecies, bonobos, and both Eastern and Western gorillas, in addition to 10 diverse humans and a high-coverage archaic Denisovan individual. This data set provides unprecedented genome-wide resolution to interrogate multiple forms of genetic variation and a unique opportunity to directly compare mutational processes and patterns of diversity in great apes.     

Pseudoephedrine and circadian rhythm interaction on neuromuscular performance

This study analyzed the effects of pseudoephedrine (PSE) provided at different time of day on neuromuscular performance, side effects, and violation of the current doping cut‐off threshold [World Anti‐Doping Agency (WADA)]. Nine resistance‐trained males carried out bench press and full squat exercises against four incremental loads (25%, 50%, 75%, and 90% one repetition maximum [1RM]), in a randomized, double‐blind, cross‐over design. Participants ingested either 180 mg of PSE (supra‐therapeutic dose) or placebo in the morning (7:00 h; AM_PLAC and AM_PSE) and in the afternoon (17:00 h; PM_PLAC and PM_PSE). PSE enhanced muscle contraction velocity against 25% and 50% 1RM loads, only when it was ingested in the mornings, and only in the full squat exercise (4.4–8.7%; P < 0.05). PSE ingestion raised urine and plasma PSE concentrations (P < 0.05) regardless of time of day; however, cathine only increased in the urine samples. PSE ingestion resulted in positive tests occurring in 11% of samples, and it rose some adverse side effects such us tachycardia and heart palpitations. Ingestion of a single dose of 180 mg of PSE results in enhanced lower body muscle contraction velocity against low and moderate loads only in the mornings. These mild performance improvements are accompanied by undesirable side effects and an 11% risk of surpassing the doping threshold.     

Combination Therapy Reverses Hyperglycemia in NOD Mice With Established Type 1 Diabetes

An increasing number of therapies have proven effective at reversing hyperglycemia in the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D), yet situations of successful translation to human T1D are limited. This may be partly due to evaluating the effect of treating immediately at diagnosis in mice, which may not be reflective of the advanced disease state in humans at disease onset. In this study, we treated NOD mice with new-onset as well as established disease using various combinations of four drugs: antithymocyte globulin (ATG), granulocyte-colony stimulating factor (G-CSF), a dipeptidyl peptidase IV inhibitor (DPP-4i), and a proton pump inhibitor (PPI). Therapy with all four drugs induced remission in 83% of new-onset mice and, remarkably, in 50% of NOD mice with established disease. Also noteworthy, disease remission occurred irrespective of initial blood glucose values and mechanistically was characterized by enhanced immunoregulation involving alterations in CD4⁺ T cells, CD8⁺ T cells, and natural killer cells. This combination therapy also allowed for effective treatment at reduced drug doses (compared with effective monotherapy), thereby minimizing potential adverse effects while retaining efficacy. This combination of approved drugs demonstrates a novel ability to reverse T1D, thereby warranting translational consideration.     

Chromatin organisation and nuclear architecture in growing mouse oocytes

Although the female gamete is blocked at the dictyate stage of the first meiotic prophase during the whole folliculogenesis, many important epigenetic changes occur to organise the genome to attend early embryonic development. In this paper, we will describe the results of a number of studies aimed to improve our understanding of the nuclear organization of the mouse oocyte during folliculogenesis. Using silver methods that stain NOR, centromeres and heterochromatin, as well as, the use of specific antibodies for the demonstration of centromeres, we have described the changes to the chromatin organisation and to the spatial localisation of chromocenters and centromeres during oocyte growth; these changes have been correlated to the developmental competence of the resulting antral and metaphase II (MII) oocyte.