AlignNemo: A Local Network Alignment Method to Integrate Homology and Topology

Local network alignment is an important component of the analysis of protein-protein interaction networks that may lead to the identification of evolutionary related complexes. We present AlignNemo, a new algorithm that, given the networks of two organisms, uncovers subnetworks of proteins that relate in biological function and topology of interactions. The discovered conserved subnetworks have a general topology and need not to correspond to specific interaction patterns, so that they more closely fit the models of functional complexes proposed in the literature. The algorithm is able to handle sparse interaction data with an expansion process that at each step explores the local topology of the networks beyond the proteins directly interacting with the current solution. To assess the performance of AlignNemo, we ran a series of benchmarks using statistical measures as well as biological knowledge. Based on reference datasets of protein complexes, AlignNemo shows better performance than other methods in terms of both precision and recall. We show our solutions to be biologically sound using the concept of semantic similarity applied to Gene Ontology vocabularies. The binaries of AlignNemo and supplementary details about the algorithms and the experiments are available at: sourceforge.net/p/alignnemo

GABA Receptors and the Pharmacology of Sleep

Current GABAergic sleep-promoting medications were developed pragmatically, without making use of the immense diversity of GABAA receptors. Pharmacogenetic experiments are leading to an understanding of the circuit mechanisms in the hypothalamus by which zolpidem and similar compounds induce sleep at α2βγ2-type GABAA receptors. Drugs acting at more selective receptor types, for example, at receptors containing the α2 and/or α3 subunits expressed in hypothalamic and brain stem areas, could in principle be useful as hypnotics/anxiolytics. A highly promising sleep-promoting drug, gaboxadol, which activates αβδ-type receptors failed in clinical trials. Thus, for the time being, drugs such as zolpidem, which work as positive allosteric modulators at GABAA receptors, continue to be some of the most effective compounds to treat primary insomnia

Pathogenesis of adolescent idiopathic scoliosis in girls - a double neuro-osseous theory involving disharmony between two nervous systems, somatic and autonomic expressed in the spine and trunk: possible dependency on sympathetic nervous system and hormones with implications for medical therapy

Anthropometric data from three groups of adolescent girls - preoperative adolescent idiopathic scoliosis (AIS), screened for scoliosis and normals were analysed by comparing skeletal data between higher and lower body mass index subsets. Unexpected findings for each of skeletal maturation, asymmetries and overgrowth are not explained by prevailing theories of AIS pathogenesis. A speculative pathogenetic theory for girls is formulated after surveying evidence including: (1) the thoracospinal concept for right thoracic AIS in girls; (2) the new neuroskeletal biology relating the sympathetic nervous system to bone formation/resorption and bone growth; (3) white adipose tissue storing triglycerides and the adiposity hormone leptin which functions as satiety hormone and sentinel of energy balance to the hypothalamus for long-term adiposity; and (4) central leptin resistance in obesity and possibly in healthy females. The new theory states that AIS in girls results from developmental disharmony expressed in spine and trunk between autonomic and somatic nervous systems. The autonomic component of this double neuro-osseous theory for AIS pathogenesis in girls involves selectively increased sensitivity of the hypothalamus to circulating leptin (genetically-determined up-regulation possibly involving inhibitory or sensitizing intracellular molecules, such as SOC3, PTP-1B and SH2B1 respectively), with asymmetry as an adverse response (hormesis); this asymmetry is routed bilaterally via the sympathetic nervous system to the growing axial skeleton where it may initiate the scoliosis deformity (leptin-hypothalamic-sympathetic nervous system concept = LHS concept). In some younger preoperative AIS girls, the hypothalamic up-regulation to circulating leptin also involves the somatotropic (growth hormone/IGF) axis which exaggerates the sympathetically-induced asymmetric skeletal effects and contributes to curve progression, a concept with therapeutic implications. In the somatic nervous system, dysfunction of a postural mechanism involving the CNS body schema fails to control, or may induce, the spinal deformity of AIS in girls (escalator concept). Biomechanical factors affecting ribs and/or vertebrae and spinal cord during growth may localize AIS to the thoracic spine and contribute to sagittal spinal shape alterations. The developmental disharmony in spine and trunk is compounded by any osteopenia, biomechanical spinal growth modulation, disc degeneration and platelet calmodulin dysfunction. Methods for testing the theory are outlined. Implications are discussed for neuroendocrine dysfunctions, osteopontin, sympathoactivation, medical therapy, Rett and Prader-Willi syndromes, infantile idiopathic scoliosis, and human evolution. AIS pathogenesis in girls is predicated on two putative normal mechanisms involved in trunk growth, each acquired in evolution and unique to humans

Exploring the factors involved in the absence of parasitism of Chaetosiphon fragaefolii by generalist parasitoids in strawberry

Chaetosiphon fragaefolii Cockerell (Hemiptera: Aphididae) is a worldwide strawberry pest with scarce records of parasitoids for its control. The parasitization rate of two generalist parasitoids, Aphidius colemani Viereck and Aphidius matricariae Haliday, their behavior and aphid defensive behaviors were evaluated with Aphis gossypii Glover (Hemiptera: Aphididae) as a comparative host. Defensive endosymbionts were also surveyed. C. fragaefolii was never parasitized in simple-choice tests, whereas in preference tests both parasitoids chose A. gossypii over C. fragaefolii. No contacts of A. matricariae with C. fragaefolii were observed while A. colemani made more antennal contacts and “stings” on A. gossypii than on C. fragaefolii with the latter exhibiting less defensive behaviors against the parasitoid. The bacterium Acinetobacter sp. was detected in all samples of C. fragaefolii, but with an unknown function. Further research on the possible defensive role of the glandular hairs covering the body of this aphid, the role of chemical signals and the existence of defensive internal mechanisms against parasitoids could provide plausible explanations for the absence of parasitism found.Instituto de Microbiología y Zoología AgrícolaFil: Francesena, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Estudios Parasitologicos y de Vectores. Universidad Nacional de la Plata. Facultad de Ciencias Naturales y Museo. Centro de Estudios Parasitologicos y de Vectores; Argentina.Fil: Arneodo Larochette, Joel Demian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Microbiología y Zoología Agrícola e Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rocca, Margarita. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Estudios Parasitologicos y de Vectores. Universidad Nacional de la Plata. Facultad de Ciencias Naturales y Museo. Centro de Estudios Parasitologicos y de Vectores; Argentina.Fil: Greco, Nancy Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Estudios Parasitologicos y de Vectores. Universidad Nacional de la Plata. Facultad de Ciencias Naturales y Museo. Centro de Estudios Parasitologicos y de Vectores; Argentina. Provincia de Buenos Aires. Comisión de Investigaciones Científicas; Argentin

Common players in mitochondria biogenesis and neuronal protection against stress-induced apoptosis

Mitochondria biogenesis is a fundamental process for the organization and normal function of all cells. Since the majority of mitochondrial proteins are synthesized in the cytosol, protein import is the major mechanism for mitochondria biogenesis. We describe the different pathways that ensure correct targeting and intra mitochondrial sorting of mitochondrial proteins. The import process of several proteins of the mitochondrial intermembrane space relies on the Mitochondrial Import and Assembly 40 and Essential for respiration and vegetative growth 1 (Erv1) proteins that together constitute the oxidative folding machinery of the mitochondrial intermembrane space. Recent work has implicated the FAD-oxidase protein Erv1 (ad its human homolog Augmenter of Liver Regeneration) as an anti-apoptotic factor in mammalian cells (including neuronal cells) that undergo Reactive Oxygen Species-triggered apoptosis. The different roles of this protein as a key factor in mitochondria biogenesis, iron-sulfur cluster biogenesis and in neuronal protection against apoptosis are discussed