Multi-level evidence of an allelic hierarchy of USH2A variants in hearing, auditory processing and speech/language outcomes.

Language development builds upon a complex network of interacting subservient systems. It therefore follows that variations in, and subclinical disruptions of, these systems may have secondary effects on emergent language. In this paper, we consider the relationship between genetic variants, hearing, auditory processing and language development. We employ whole genome sequencing in a discovery family to target association and gene x environment interaction analyses in two large population cohorts; the Avon Longitudinal Study of Parents and Children (ALSPAC) and UK10K. These investigations indicate that USH2A variants are associated with altered low-frequency sound perception which, in turn, increases the risk of developmental language disorder. We further show that Ush2a heterozygote mice have low-level hearing impairments, persistent higher-order acoustic processing deficits and altered vocalizations. These findings provide new insights into the complexity of genetic mechanisms serving language development and disorders and the relationships between developmental auditory and neural systems

Comparative radiological features of disseminated disease due to Mycobacterium tuberculosis vs non-tuberculosis mycobacteria among AIDS patients in Brazil

Background: Disseminated mycobacterial disease is an important cause of morbidity and mortality in patients with HIV-infection. Nonspecific clinical presentation makes the diagnosis difficult and sometimes neglected. Methods: We conducted a retrospective cohort study to compare the presentation of disseminated Mycobacterial tuberculosis (MTB) and non-tuberculous Mycobacterial (NTM) disease in HIV-positive patients from 1996 to 2006 in Brazil. Results: Tuberculosis (TB) was diagnosed in 65 patients (67.7%) and NTM in 31 (32.3%) patients. Patients with NTM had lower CD4 T cells counts (median 13.0 cells/mm3 versus 42.0 cells/mm3, P = 0.002). Patients with tuberculosis had significantly more positive acid-fast smears (48.0% vs 13.6%, P = 0.01). On chest X-ray, miliary infiltrate was only seen in patients with MTB (28.1% vs. 0.0%, P = 0.01). Pleural effusion was more common in patients with MTB (45.6% vs. 13.0%, P = 0.01). Abdominal adenopathy (73.1% vs. 33.3%, P = 0.003) and splenic hypoechoic nodules (38.5% vs. 0.0%, P = 0.002) were more common in patients with TB. Conclusion: Miliary pulmonary pattern on X-ray, pleural effusion, abdominal adenopathy, and splenic hypoechoic nodules were imaging findings associated with the diagnosis of tuberculosis in HIV-infected patients. Recognition of these imaging features will help to distinguish TB from NTM in AIDS patients with fever of unknown origin due to disseminated mycobacterial disease

An OLG model of growth with longevity : when grandparents take care of grandchildren

By assuming that grandparents take care of grandchildren, this paper aims at studying the effects of longevity on long-term economic growth in a model with overlapping generations and endogenous fertility. We show that an increase in longevity may: (i) reduce the long-term economic growth; (ii) increase the supply of labour, and (iii) cause fertility either to increase of decrease depending on the size of time spent by grandparents to rise grandchildren. These findings also hold in an endogenous growth setting a` la Romer (J Polit Econ 94:1002–1037, 1986).info:eu-repo/semantics/publishedVersio

Novel Exon of Mammalian ADAR2 Extends Open Reading Frame

Background: The post-transcriptional processing of pre-mRNAs by RNA editing contributes significantly to the complexity of the mammalian transcriptome. RNA editing by site-selective A-to-I modification also regulates protein function through recoding of genomically specified sequences. The adenosine deaminase ADAR2 is the main enzyme responsible for recoding editing and loss of ADAR2 function in mice leads to a phenotype of epilepsy and premature death. Although A-to-I RNA editing is known to be subject to developmental and cell-type specific regulation, there is little knowledge regarding the mechanisms that regulate RNA editing in vivo. Therefore, the characterization of ADAR expression and identification of alternative ADAR variants is an important prerequisite for understanding the mechanisms for regulation of RNA editing and the causes for deregulation in disease. Methodology/Principal Findings: Here we present evidence for a new ADAR2 splice variant that extends the open reading frame of ADAR2 by 49 amino acids through the utilization of an exon located 18 kilobases upstream of the previously annotated first coding exon and driven by a candidate alternative promoter. Interestingly, the 49 amino acid extension harbors a sequence motif that is closely related to the R-domain of ADAR3 where it has been shown to function as a basic, single-stranded RNA binding domain. Quantitative expression analysis shows that expression of the novel ADAR2 splice variant is tissue specific being highest in the cerebellum

Incomplete gastric metaplasia in children with insulin-dependent diabetes mellitus and celiac disease. An ultrastructural study

BACKGROUND: The association of insulin-dependent diabetes mellitus (IDDM) and celiac disease (CD) has been widely reported in children but the relationship between the two conditions is incompletely understood. Moreover, specific studies on intestinal biopsies of patients with the association of the two diseases are still lacking. METHODS: We studied the ultrastructure of the duodenal mucosa in 12 patients with both IDDM and CD. RESULTS: All patients had either total or partial atrophy of duodenal mucosa. In seven subjects, an accumulation of electrondense granules in the apical cytoplasm of groups of enterocytes was found. In four of them, a double population of granules existed (mean diameter: 400-800 nm and 100-200 nm respectively) showing a biphasic pattern. In the other three patients, only smaller granules (100- 200 nm) were found in the enterocytes. CONCLUSIONS: The present work suggests that patients with IDDM/CD may represent a subgroup in the context of the CD population. Intestinal biopsies of such individuals often show accumulation of electrondense granules in the apical cytoplasm of enterocytes that can be interpreted as incomplete gastric metaplasia

Muscle protein metabolism in neonatal alloxan-administered rats: effects of continuous and intermittent swimming training

<p>Abstract</p> <p>Background</p> <p>This study aimed to examine the effects of intermittent and continuous swimming training on muscle protein metabolism in neonatal alloxan-administered rats.</p> <p>Methods</p> <p>Wistar rats were used and divided into six groups: sedentary alloxan (SA), sedentary control (SC), continuous trained alloxan (CA), intermittent trained alloxan (IA), continuous trained control (CC) and intermittent trained control (IC). Alloxan (250 mg/kg body weight) was injected into newborn rats at 6 days of age. The continuous training protocol consisted of 12 weeks of swimming training in individual cylinder tanks while supporting a load that was 5% of body weight; uninterrupted swimming for 1 h/day, five days a week. The intermittent training protocol consisted of 12 weeks of swimming training in individual cylinder tanks while supporting a load that was 15% of body weight; 30 s of activity interrupted by 30 s of rest for a total of 20 min/day, five days a week.</p> <p>Results</p> <p>At 28 days, the alloxan animals displayed higher glycemia after glucose overload than the control animals. No differences in insulinemia among the groups were detected. At 120 days, no differences in serum albumin and total protein among the groups were observed. Compared to the other groups, DNA concentrations were higher in the alloxan animals that were subjected to continuous training, whereas the DNA/protein ratio was higher in the alloxan animals that were subjected to intermittent training.</p> <p>Conclusion</p> <p>It was concluded that continuous and intermittent training sessions were effective in altering muscle growth by hyperplasia and hypertrophy, respectively, in alloxan-administered animals.</p

Comparison of Epithelial Differentiation and Immune Regulatory Properties of Mesenchymal Stromal Cells Derived from Human Lung and Bone Marrow

Mesenchymal stromal cells (MSCs) reside in many organs including lung, as shown by their isolation from fetal lung tissues, bronchial stromal compartment, bronchial-alveolar lavage and transplanted lung tissues. It is still controversial whether lung MSCs can undergo mesenchymal-to-epithelial-transition (MET) and possess immune regulatory properties. To this aim, we isolated, expanded and characterized MSCs from normal adult human lung (lung-hMSCs) and compared with human bone marrow-derived MSCs (BM-hMSCs). Our results show that lung-MSCs reside at the perivascular level and do not significantly differ from BM-hMSCs in terms of immunophenotype, stemness gene profile, mesodermal differentiation potential and modulation of T, B and NK cells. However, lung-hMSCs express higher basal level of the stemness-related marker nestin and show, following in vitro treatment with retinoic acid, higher epithelial cell polarization, which is anyway partial when compared to a control epithelial bronchial cell line. Although these results question the real capability of acquiring epithelial functions by MSCs and the feasibility of MSC-based therapeutic approaches to regenerate damaged lung tissues, the characterization of this lung-hMSC population may be useful to study the involvement of stromal cell compartment in lung diseases in which MET plays a role, such as in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis

Factors influencing gastrointestinal tract and microbiota immune interaction in preterm infants

The role of microbial colonization is indispensable for keeping a balanced immune response in life. However, the events that regulate the establishment of the microbiota, their timing, and the way in which they interact with the host are not yet fully understood. Factors such as gestational age, mode of delivery, environment, hygienic measures, and diet influence the establishment of microbiota in the perinatal period. Environmental microbes constitute the most important group of exogenous stimuli in this critical time frame. However, the settlement of a stable gut microbiota in preterm infants is delayed compared to term infants. Preterm infants have an immature gastrointestinal tract and immune system which predisposes to infectious morbidity. Neonatal microbial dynamics and alterations in early gut microbiota may precede and/or predispose to diseases such as necrotizing enterocolitis (NEC), late-onset sepsis or others. During this critical period, nutrition is the principal contributor for immunological and metabolic development, and microbiological programming. Breast milk is a known source of molecules that act synergistically to protect the gut barrier and enhance the maturation of the gut-related immune response. Host-microbe interactions in preterm infants and the protective role of diet focused on breast milk impact are beginning to be unveiled.M.C. acknowledges a “Rio Hortega” Research Fellowship Grant (CM13/0017) and M.V. acknowledges grants PI11/0313 and RD12/0026/0012 (Red SAMID) from the Instituto Carlos III (Spanish Ministry of Economy and Competitivity). M.C.C. and G.P-M. were supported by the grant AGL2013-47420-R from the Spanish Ministry of Science and Innovation.Peer reviewe

Genomic analysis of family data reveals additional genetic effects on intelligence and personality

BioRXiv version. Please see https://rubenarslan.github.io/generation_scotland_pedigree_gcta/ to access this website in a browsable form