Computational neuroscience and neuroinformatics: Recent progress and resources

The human brain and its temporal behavior correlated with development, structure, and function is a complex natural system even for its own kind. Coding and automation are necessary for modeling, analyzing and understanding the 86.1 ± 8.1 billion neurons, an almost equal number of non-neuronal glial cells, and the neuronal networks of the human brain comprising about 100 trillion connections. ‘Computational neuroscience’ which is heavily dependent on biology, physics, mathematics and computation addresses such problems while the archival, retrieval and merging of the huge amount of generated data in the form of clinical records, scientific literature, and specialized databases are carried out by ‘neuroinformatics’ approaches. Neuroinformatics is thus an interface between computer science and experimental neuroscience. This article provides an introduction to computational neuroscience and neuroinformatics fields along with their state-of-the-art tools, software, and resources. Furthermore, it describes a few innovative applications of these fields in predicting and detecting brain network organization, complex brain disorder diagnosis, large-scale 3D simulation of the brain, brain–computer, and brain-to-brain interfaces. It provides an integrated overview of the fields in a non-technical way, appropriate for broad general readership. Moreover, the article is an updated unified resource of the existing knowledge and sources for researchers stepping into these fields.     

Towards a comprehensive understanding of the Si(100)-2×1 surface termination through hydrogen passivation using methylamine and methanol: a theoretical approach

Using density functional theory, we explored the termination process of Si (100)-2?×?1 reconstructed surface mechanistically through the dehydrogenation of small molecules, considering methyl amine and methanol as terminating reagents. At first, both the terminating reagents form two types of adduct through adsorption on the Si (100)-2?×?1 surface, one in chemisorption mode and the other via physisorption, from which the dehydrogenation process is initiated. By analyzing the activation barriers, it was observed that termination of the Si-surface through the dehydrogenation is kinetically almost equally feasible using either reagent. We further examined in detail the mechanism for each termination process by analyzing geometrical parameters and natural population analysis charges. From bonding evaluation, it is evident that hydrogen abstraction from adsorbates on the Si-surface is asymmetric in nature, where one hydrogen is abstracted as hydride by the electrophilic surface Si and the other hydrogen is abstracted as proton by the neucleophilic surface Si. Moreover, it was also observed that hydride transfer from adsorbate to the Si-surface occurs first followed by proton transfer. Overall, our theoretical interpretation provides a mechanistic understanding of the Si (100)-2?×?1 reconstructed surface termination by amine and alcohol that will further motivate researchers to design different types of decorated semiconductor devices.

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Graphical Abstract Surface termination process of Si(100)-2×1 through formation of non-polar Si–H bonds via dehydrogenation of methylamine and methanol as terminating reagents

     

An annotated checklist of Culicoides Latreille, 1809 (Insecta: Ceratopogonidae: Diptera) with incorporation of a vector species list from India

Culicoides Latreille, 1809 (Insecta : Diptera : Ceratopogonidae) are small nematocerous biological vectors of a wide range of pathogens of veterinary and medical importance. They are distributed worldwide but prefer warm, damp, and muddy areas. Female midges require blood for egg maturation. Studies on taxonomy, proper identification keys, and distribution patterns of these flies across different geographical regions of India of these flies are limited. This article provides an updated checklist of Culicoides spp. from India collected from various scattered publications, along with their synonyms and details on their subgenera, geographical distribution, and type locality. A compiled list of different Culicoides vectors from India has also been included separately in this article, along with the type of the diseases spread.     

Critical Molecular Determinants of α7 Nicotinic Acetylcholine Receptor Allosteric Activation: SEPARATION OF DIRECT ALLOSTERIC ACTIVATION AND POSITIVE ALLOSTERIC MODULATION*

The α7 nicotinic acetylcholine receptors (nAChRs) are uniquely sensitive to selective positive allosteric modulators (PAMs), which increase the efficiency of channel activation to a level greater than that of other nAChRs. Although PAMs must work in concert with “orthosteric” agonists, compounds such as GAT107 ((3aR,4S,9bS)-4-(4-bromophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-sulfonamide) have the combined properties of agonists and PAMs (ago-PAM) and produce very effective channel activation (direct allosteric activation (DAA)) by operating at two distinct sites in the absence of added agonist. One site is likely to be the same transmembrane site where PAMs like PNU-120596 function. We show that the other site, required for direct activation, is likely to be solvent-accessible at the extracellular domain vestibule. We identify key attributes of molecules in this family that are able to act at the DAA site through variation at the aryl ring substituent of the tetrahydroquinoline ring system and with two different classes of competitive antagonists of DAA. Analyses of molecular features of effective allosteric agonists allow us to propose a binding model for the DAA site, featuring a largely non-polar pocket accessed from the extracellular vestibule with an important role for Asp-101. This hypothesis is supported with data from site-directed mutants. Future refinement of the model and the characterization of specific GAT107 analogs will allow us to define critical structural elements that can be mapped onto the receptor surface for an improved understanding of this novel way to target α7 nAChR therapeutically.     

Comparison among four triazole fungicides on growth and development of sheath blight of rice pathogen Rhizoctonia solani Kühn AG1-1A

The sheath blight of rice pathogen Rhizoctonia solani Kühn AG1-1A has long been known as a major crisis in global rice production. The present study aimed to compare the efficacy of four triazole fungicides at different doses on the growth and development of R. solani Kühn AG1-1A. Obtained results demonstrated inhibitory effects of all four fungicides on mycelial growth, sclerotia formation and biomass production of R. solani Kühn AG1-1A with significant variation among the treatment doses as well as fungicide molecules (p ≤ 0.05). At the respective EC₅₀ doses all four fungicides inhibited cell wall degrading enzymes viz. invertase, cellulase, polygalacturonase and pectin lyase, of the sheath blight pathogen. The extent of inhibition of the enzymes significantly varied among the fungicides. It is important to note that in spite of having common mode of action, all four triazole fungicides demonstrated significant variation in their fungicidal efficacy on R. solani Kühn AG1-1A.     

Goat mammary epithelial cells provide a better expression system for production of recombinant human bone morphogenetic protein 2 compared to Chinese hamster ovarian cells

Bone Morphogenetic Protein 2 (BMP2), a member of the Transforming Growth Factor-β (TGF-β) super family of proteins and is instrumental in the repair of fractures. The synthesis of BMP2 involves extensive post-translational processing and several studies have demonstrated the abysmally low production of rhBMP2 in eukaryotic systems, which may be due to the short half-life of the bioactive protein. Consequently, production costs of rhBMP2 are quite high, limiting its availability to the general populace. Therefore, there is an urgent need to identify better in-vitro systems for large scale production of rhBMP2. In the present study, we have carried out a comparative analysis of rhBMP2 production by the conventionally used Chinese Hamster ovarian cells (CHO) and goat mammary epithelial cells (GMEC), upon transfection with appropriate construct. Udder gland cells are highly secretory, and we reasoned that such cells may serve as a better in-vitro model for large scale production of rhBMP2. Our results indicated that the synthesis and secretion of bioactive rhBMP2 by goat mammary epithelial cells was significantly higher as compared to that by CHO-K1 cells. Our results provide strong evidence that GMECs may serve as a better alternative to other mammalian cells used for therapeutic protein production.