Whole-Exome Sequencing and Homozygosity Analysis Implicate Depolarization-Regulated Neuronal Genes in Autism

Although autism has a clear genetic component, the high genetic heterogeneity of the disorder has been a challenge for the identification of causative genes. We used homozygosity analysis to identify probands from nonconsanguineous families that showed evidence of distant shared ancestry, suggesting potentially recessive mutations. Whole-exome sequencing of 16 probands revealed validated homozygous, potentially pathogenic recessive mutations that segregated perfectly with disease in 4/16 families. The candidate genes (UBE3B, CLTCL1, NCKAP5L, ZNF18) encode proteins involved in proteolysis, GTPase-mediated signaling, cytoskeletal organization, and other pathways. Furthermore, neuronal depolarization regulated the transcription of these genes, suggesting potential activity-dependent roles in neurons. We present a multidimensional strategy for filtering whole-exome sequence data to find candidate recessive mutations in autism, which may have broader applicability to other complex, heterogeneous disorders

Analysis of Adhesion Molecules and Basement Membrane Contributions to Synaptic Adhesion at the Drosophila Embryonic NMJ

Synapse formation and maintenance crucially underlie brain function in health and disease. Both processes are believed to depend on cell adhesion molecules (CAMs). Many different classes of CAMs localise to synapses, including cadherins, protocadherins, neuroligins, neurexins, integrins, and immunoglobulin adhesion proteins, and further contributions come from the extracellular matrix and its receptors. Most of these factors have been scrutinised by loss-of-function analyses in animal models. However, which adhesion factors establish the essential physical links across synaptic clefts and allow the assembly of synaptic machineries at the contact site in vivo is still unclear. To investigate these key questions, we have used the neuromuscular junction (NMJ) of Drosophila embryos as a genetically amenable model synapse. Our ultrastructural analyses of NMJs lacking different classes of CAMs revealed that loss of all neurexins, all classical cadherins or all glutamate receptors, as well as combinations between these or with a Laminin deficiency, failed to reveal structural phenotypes. These results are compatible with a view that these CAMs might have no structural role at this model synapse. However, we consider it far more likely that they operate in a redundant or well buffered context. We propose a model based on a multi-adaptor principle to explain this phenomenon. Furthermore, we report a new CAM-independent adhesion mechanism that involves the basement membranes (BM) covering neuromuscular terminals. Thus, motorneuronal terminals show strong partial detachment of the junction when BM-to-cell surface attachment is impaired by removing Laminin A, or when BMs lose their structural integrity upon loss of type IV collagens. We conclude that BMs are essential to tie embryonic motorneuronal terminals to the muscle surface, lending CAM-independent structural support to their adhesion. Therefore, future developmental studies of these synaptic junctions in Drosophila need to consider the important contribution made by BM-dependent mechanisms, in addition to CAM-dependent adhesion

The spatial structure of lithic landscapes : the late holocene record of east-central Argentina as a case study

Fil: Barrientos, Gustavo. División Antropología. Facultad de Ciencias Naturales y Museo. Universidad Nacional de La Plata; ArgentinaFil: Catella, Luciana. División Arqueología. Facultad de Ciencias Naturales y Museo. Universidad Nacional de La Plata; ArgentinaFil: Oliva, Fernando. Centro Estudios Arqueológicos Regionales. Facultad de Humanidades y Artes. Universidad Nacional de Rosario; Argentin

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Effect of parity on oestrus synchronization success in cows

The objective of the present study wits to evaluate the effect of parity on pregnancy rate in lactating Holstein cows Subjected to different synchronization protocols. A total of 96 cows (49 primiparous and 47 multiparous) were allocated randomly into four groups containing primiparous and multiparous COWS. In the PRID group (n=23), progesterone releasing intravaginal device (PRID) was inserted into anterior vagina of the cows. The devices Were removed 12 days later and 500 mu g of cloprostenol was intramuscularly administered the day before PRID withdrawal. In the Implant group (n=25), ear implants releasing norgestomet were Subcutaneously g inserted in the Car of each cow for 9 days and 500 mu g of cloprostenol was intramuscularly administered the day before the implant removal. In the GnRH group (n=24), buserelin, a GnRH analogue 10 mu g was given oil day 0 followed by the administration of 500 mu g of cloprostenol, 7 days later. In the PGF(2 alpha) group (n=24), two intramuscular administrations of 500 mu g of cloprostenol were performed at an 11-day interval. All cows exhibited oestrus signs between 36 and 124 h after the last PGF(2 alpha) administration

Esterified glucomannan improves aflatoxin-induced damage of sperm parameters during liquid storage of ram semen at 5°C.

The aim of the present work was to study the effects of aflatoxin (AF) on sperm parameters in rams, and to determine the protective efficiency of esterified glucomannan (EG) co-administered with AF up to 96 h of the liquid storage of ram semen at 5°C. Thirty-two Merino rams (12-14 months old) were used. The animals were examined for their general health status. To ensure their adaptation to the environment and the new feeding regimen, a 15-day acclimatization programme was applied to the animals, prior to the start of the study. Experimental feeding was continued for ninety-two days. The experimental design consisted of four dietary treatments. The control group (C) was fed with commercial feed. The AF group was fed with commercial feed plus 250 μg/day of total AF. The EG group received commercial feed plus 2g/day of EG. The AF + EG group was given commercial feed plus 250 μg/day of total AF and 2g/day of EG. In the study, ejaculates were obtained from rams twice a week for 12 weeks, using an electro-ejaculator. After collected, the ejaculates were diluted with a skimmed milk extender, and stored at 5°C. Sperm motility and rates of abnormal and nonviable spermatozoa were determined for the different treatment groups at 5°C at 0, 24, 48, 72 and 96 h of liquid storage. During the first two weeks of the trial, the groups did not statistically differ from each other for sperm motility or rates of abnormal and nonviable spermatozoa at 0, 24, 48 and 96 h of storage. As from the third week, the short-term storage of semen produced statistically significant differences between the AF group and the other treatment groups for sperm parameters (p<0.05). The administration of aflatoxin was observed to have reduced sperm motility and to have increased the rates of abnormal and nonviable spermatozoa in comparison to the control group (p<0.05), while EG co-administered with AF was determined to have ameliorated the adverse effects of AF on sperm parameters, and this ameliorative effect continued throughout the short-term storage of semen. On the other hand, aflatoxin administration resulted in the deterioration of the sperm parameters in the following weeks, and the combined administration of EG + AF reversed this adverse effect, thus, bringing the sperm parameters closer to the values of the control group. This study demonstrated that, in rams, AF adversely affected sperm, biochemical and testis parameters, and that the combined administration of EG and AF reversibly improved these adverse effects