The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism

Although multiple reports show that defective genetic networks underlie the aetiology of autism, few have translated into pharmacotherapeutic opportunities. Since drugs compete with endogenous small molecules for protein binding, many successful drugs target large gene families with multiple drug binding sites. Here we search for defective gene family interaction networks (GFINs) in 6,742 patients with the ASDs relative to 12,544 neurologically normal controls, to find potentially druggable genetic targets. We find significant enrichment of structural defects (P≤2.40E-09, 1.8-fold enrichment) in the metabotropic glutamate receptor (GRM) GFIN, previously observed to impact attention deficit hyperactivity disorder (ADHD) and schizophrenia. Also, the MXD-MYC-MAX network of genes, previously implicated in cancer, is significantly enriched (P≤3.83E-23, 2.5-fold enrichment), as is the calmodulin 1 (CALM1) gene interaction network (P≤4.16E-04, 14.4-fold enrichment), which regulates voltage-independent calcium-activated action potentials at the neuronal synapse. We find that multiple defective gene family interactions underlie autism, presenting new translational opportunities to explore for therapeutic interventions

Genome of Herbaspirillum seropedicae Strain SmR1, a Specialized Diazotrophic Endophyte of Tropical Grasses

The molecular mechanisms of plant recognition, colonization, and nutrient exchange between diazotrophic endophytes and plants are scarcely known. Herbaspirillum seropedicae is an endophytic bacterium capable of colonizing intercellular spaces of grasses such as rice and sugar cane. The genome of H. seropedicae strain SmR1 was sequenced and annotated by The Paraná State Genome Programme—GENOPAR. The genome is composed of a circular chromosome of 5,513,887 bp and contains a total of 4,804 genes. The genome sequence revealed that H. seropedicae is a highly versatile microorganism with capacity to metabolize a wide range of carbon and nitrogen sources and with possession of four distinct terminal oxidases. The genome contains a multitude of protein secretion systems, including type I, type II, type III, type V, and type VI secretion systems, and type IV pili, suggesting a high potential to interact with host plants. H. seropedicae is able to synthesize indole acetic acid as reflected by the four IAA biosynthetic pathways present. A gene coding for ACC deaminase, which may be involved in modulating the associated plant ethylene-signaling pathway, is also present. Genes for hemagglutinins/hemolysins/adhesins were found and may play a role in plant cell surface adhesion. These features may endow H. seropedicae with the ability to establish an endophytic life-style in a large number of plant species

Four-and-a-half LIM domains protein 2 (FHL2) is associated with the development of craniofacial musculature in the teleost fish Sparus aurata

Four-and-a-half LIM domains protein 2 (FHL2) is involved in major cellular mechanisms such as regulation of gene transcription and cytoskeleton modulation, participating in physiological control of cardiogenesis and osteogenesis. Knowledge on underlying mechanisms is, however, limited. We present here new data on FHL2 protein and its role during vertebrate development using a marine teleost fish, the gilthead seabream (Sparus aurata L.). In silico comparison of vertebrate protein sequences and prediction of LIM domain three-dimensional structure revealed a high degree of conservation, suggesting a conserved function throughout evolution. Determination of sites and levels of FHL2 gene expression in seabream indicated a central role for FHL2 in the development of heart and craniofacial musculature, and a potential role in tissue calcification. Our data confirmed the key role of FHL2 protein during vertebrate development and gave new insights into its particular involvement in craniofacial muscle development and specificity for slow fibers

Tetraselmis suecica and Tisochrysis lutea meal as dietary ingredients for gilthead sea bream (Sparus aurata L.) fry.

In the present study, the nutritional value of Tetraselmis suecica and Tisochrysis lutea (previously known as Isochrysis aff galbana T-ISO strain) freeze-dried biomass for feeding Sparus aurata fry was evaluated. A total of 25,500 fry (3.7 mg body weight) were fed for 55 days on diets containing 5 and 10%(w/w) Tetraselmis or Tisochrysis, as well as on a microalgae-free diet. Fish fed 5 % Tetraselmis showed higher growth performance, nutrient utilization, and survival values than fish fed Tisochrysis. The use of microalgae significantly decreased the body lipid content in fry fed the highest microalgae level. Fry fed Tisochrysis-supplemented diets increased the DHA content in muscle, and consequently the EPA/DHA ratio decreased significantly, whatever dietary level considered. In general, digestive protease activities were not adversely affected by dietary microalgae inclusion, although slight variations were observed during fish development. Microalgae utilization causes a positive effect on intestinal mucosa ultrastructure owing to an increase of total enterocyte absorption surface that was observed in fish fed microalgae-supplemented diets. Cluster analysis of data separated clearly fish fed Tisochrysis-supplemented diets from the rest of experimental groups. This study confirms that Tetraselmis freeze-dried biomass can be used as dietary ingredient in started feeds for S. aurata fry, although an inclusion level of 5 % is recommended.Versión del editor2,326