Functional Phenotypic Rescue of Caenorhabditis elegans Neuroligin-Deficient Mutants by the Human and Rat NLGN1 Genes

Neuroligins are cell adhesion proteins that interact with neurexins at the synapse. This interaction may contribute to differentiation, plasticity and specificity of synapses. In humans, single mutations in neuroligin encoding genes lead to autism spectrum disorder and/or mental retardation. Caenorhabditis elegans mutants deficient in nlg-1, an orthologue of human neuroligin genes, have defects in different behaviors. Here we show that the expression of human NLGN1 or rat Nlgn1 cDNAs in C. elegans nlg-1 mutants rescues the fructose osmotic strength avoidance and gentle touch response phenotypes. Two specific point mutations in NLGN3 and NLGN4 genes, involved in autistic spectrum disorder, were further characterized in this experimental system. The R451C allele described in NLGN3, was analyzed with both human NLGN1 (R453C) and worm NLG-1 (R437C) proteins, and both were not functional in rescuing the osmotic avoidance behavior and the gentle touch response phenotype. The D396X allele described in NLGN4, which produces a truncated protein, was studied with human NLGN1 (D432X) and they did not rescue any of the behavioral phenotypes analyzed. In addition, RNAi feeding experiments measuring gentle touch response in wild type strain and worms expressing SID-1 in neurons (which increases the response to dsRNA), both fed with bacteria expressing dsRNA for nlg-1, provided evidence for a postsynaptic in vivo function of neuroligins both in muscle cells and neurons, equivalent to that proposed in mammals. This finding was further confirmed generating transgenic nlg-1 deficient mutants expressing NLG-1 under pan-neuronal (nrx-1) or pan-muscular (myo-3) specific promoters. All these results suggest that the nematode could be used as an in vivo model for studying particular synaptic mechanisms with proteins orthologues of humans involved in pervasive developmental disorders

Common Variants of TLR1 Associate with Organ Dysfunction and Sustained Pro-Inflammatory Responses during Sepsis

Background: Toll-like receptors (TLRs) are critical components for host pathogen recognition and variants in genes participating in this response influence susceptibility to infections. Recently, TLR1 gene polymorphisms have been found correlated with whole blood hyper-inflammatory responses to pathogen-associated molecules and associated with sepsis-associated multiorgan dysfunction and acute lung injury (ALI). We examined the association of common variants of TLR1 gene with sepsis-derived complications in an independent study and with serum levels for four inflammatory biomarker among septic patients. Methodology/Principal Findings: Seven tagging single nucleotide polymorphisms of the TLR1 gene were genotyped in samples from a prospective multicenter case-only study of patients with severe sepsis admitted into a network of intensive care units followed for disease severity. Interleukin (IL)-1 b, IL-6, IL-10, and C-reactive protein (CRP) serum levels were measured at study entry, at 48 h and at 7th day. Alleles -7202G and 248Ser, and the 248Ser-602Ile haplotype were associated with circulatory dysfunction among severe septic patients (0.001<=p <= 0.022), and with reduced IL-10 (0.012<= p <=0.047) and elevated CRP (0.011<= p <=0.036) serum levels during the first week of sepsis development. Additionally, the -7202GG genotype was found to be associated with hospital mortality (p =0.017) and ALI (p =0.050) in a combined analysis with European Americans, suggesting common risk effects among studies Conclusions/Significance: These results partially replicate and extend previous findings, supporting that variants of TLR1 gene are determinants of severe complications during sepsis

Destination memory and familiarity: better memory for conversations with Elvis Presley than with unknown people

Background and aims Familiarity is assumed to exert a beneficial effect on memory in older adults. Our paper investigated this issue specifically for destination memory, that is, memory of the destination of previously relayed information. Methods Young and older adults were told familiar (Experiment 1) and unfamiliar (Experiment 2) proverbs associated with pictures depicting faces of celebrities (e.g., Elvis Presley) or unknown people, with a specific proverb assigned to each face. In a later recognition task, participants were presented with the previously exposed proverb–face pairs and for each pair had to decide whether they had previously relayed the given proverb to the given face. Results In general, destination performance was found to be higher for familiar than for unfamiliar faces. However while there was no difference between the two groups when the proverbs being relayed were unfamiliar, the advantage of face familiarity on destination memory was present only for older adults when the proverbs being relayed were familiar. Discussion and conclusions Our results show that destination memory in older adults is sensitive to familiarity of both destination and output information

Evaluation of filtering blebs using the ‘Wuerzburg bleb classification score’ compared to clinical findings

Background To determine the agreement between intraocular pressure and the ‘Wuerzburg bleb classification score’, as well as between single items of the score and intraocular pressure. Interobserver variability was analyzed. Methods 57 post-trabeculectomy eyes were included. Colour photographs were used to score the filtering bleb in accordance to the Wuerzburg bleb classification score by two different examiners. At the same visit, clinical data such as intraocular pressure, best corrected visual acuity, slit lamp biomicroscopy and medical history were obtained by another examiner. Results After trabeculectomy, 42 out of 57 eyes (73.7%) reached the target pressure (≤21mmHg, and intraocular pressure reduction of at least 20%, without antiglaucoma medication, and without any additional intervention). Fair agreement was found between intraocular pressure and Wuerzburg bleb classification score ≥8 points and ≥7 points (kappa 0.24 and 0.27, respectively). Analyzing the subgroups of the morphological criteria, best agreement was found between occurrence of microcysts and target intraocular pressure (к 0.22 – 0.34). Conclusions Evaluating filtering blebs after trabeculectomy by using the Wuerzburg bleb classification score is a good technique for predicting intraocular pressure control in eyes attaining a minimum score of seven points. The presence of microcysts on the filtering bleb predicts that the eye is likely to attain target pressure