Analysis of the human protein interactome and comparison with yeast, worm and fly interaction datasets

We present the first analysis of the human proteome with regard to interactions between proteins. We also compare the human interactome with the available interaction datasets from yeast (Saccharomyces cerevisiae), worm (Caenorhabditis elegans) and fly (Drosophila melanogaster). Of >70,000 binary interactions, only 42 were common to human, worm and fly, and only 16 were common to all four datasets. An additional 36 interactions were common to fly and worm but were not observed in humans, although a coimmunoprecipitation assay showed that 9 of the interactions do occur in humans. A re-examination of the connectivity of essential genes in yeast and humans indicated that the available data do not support the presumption that the number of interaction partners can accurately predict whether a gene is essential. Finally, we found that proteins encoded by genes mutated in inherited genetic disorders are likely to interact with proteins known to cause similar disorders, suggesting the existence of disease subnetworks. The human interaction map constructed from our analysis should facilitate an integrative systems biology approach to elucidating the cellular networks that contribute to health and disease states.     

Atomic model of the type III secretion system needle

Pathogenic bacteria using a type III secretion system (T3SS) to manipulate host cells cause many different infections including Shigella dysentery, typhoid fever, enterohaemorrhagic colitis and bubonic plague. An essential part of the T3SS is a hollow needle-like protein filament through which effector proteins are injected into eukaryotic host cells. Currently, the three-dimensional structure of the needle is unknown because it is not amenable to X-ray crystallography and solution NMR, as a result of its inherent non-crystallinity and insolubility. Cryo-electron microscopy combined with crystal or solution NMR subunit structures has recently provided a powerful hybrid approach for studying supramolecular assemblies, resulting in low-resolution and medium-resolution models. However, such approaches cannot deliver atomic details, especially of the crucial subunit-subunit interfaces, because of the limited cryo-electron microscopic resolution obtained in these studies. Here we report an alternative approach combining recombinant wild-type needle production, solid-state NMR, electron microscopy and Rosetta modelling to reveal the supramolecular interfaces and ultimately the complete atomic structure of the Salmonella typhimurium T3SS needle. We show that the 80-residue subunits form a right-handed helical assembly with roughly 11 subunits per two turns, similar to that of the flagellar filament of S. typhimurium. In contrast to established models of the needle in which the amino terminus of the protein subunit was assumed to be α-helical and positioned inside the needle, our model reveals an extended amino-terminal domain that is positioned on the surface of the needle, while the highly conserved carboxy terminus points towards the lumen.     

High-energy ion treatments of amorphous As40Se60 thin films for optical applic ations

The treatment of 100 MeV Ag swift-heavy ion(SHI) irradiation with five different fluences(3 1010, 1 1011, 3 1011, 1 1012, and3 1012ions/cm2) was used to design optical and structural properties of amorphous(a-) As40Se60 chalcogenide thin films. Swanepoel method was applied on transmission measurements to determine the changes in optical bandgap, Tauc parameter and linear optical parameters, i.e., linear optical absorption, extinction coefficient and linear refractive index. Dispersion of the material was determined by Wemple–DiDomenico relation.Changes in nonlinear optical parameters of third-order optical susceptibility and nonlinear refractive index were determined using semi-empirical relations. Changes in surface morphology of the films were investigated using SEM observation, which indicated that fluence 3 1012ions/cm2was upper threshold limit for these films for ion treatment. It is observed that optical bandgap reduces from 1.76 eV to 1.64 eV, and nonlinear refractive index increases from 1.31 10 10[esu] to 1.74 10 10[esu]. Linear refractive index initially increases from 2.80 to 3.52(for fluence3 1010ions/cm2) and then keeps decreasing. The observed changes in optical properties upon irradiation were explained in terms of structural rearrangements by Raman measurement. The study was compiled with the previous literature to propose SHI as an effective optical engineering technique to achieve desired changes according to the need of optical/photonic applications.     

Multiple apical plasma membrane constituents are associated with susceptibility to meconium ileus in individuals with cystic fibrosis

Variants associated with meconium ileus in cystic fibrosis were identified in 3,763 affected individuals by genome-wide association study (GWAS). Five SNPs at two loci near SLC6A14 at Xq23-24 (minimum P = 1.28 × 10(-12) at rs3788766) and SLC26A9 at 1q32.1 (minimum P = 9.88 × 10(-9) at rs4077468) accounted for ~5% of phenotypic variability and were replicated in an independent sample of affected individuals (n = 2,372; P = 0.001 and 0.0001, respectively). By incorporating the knowledge that disease-causing mutations in CFTR alter electrolyte and fluid flux across surface epithelium into a hypothesis-driven GWAS (GWAS-HD), we identified associations with the same SNPs in SLC6A14 and SLC26A9 and established evidence for the involvement of SNPs in a third solute carrier gene, SLC9A3. In addition, GWAS-HD provided evidence of association between meconium ileus and multiple genes encoding constituents of the apical plasma membrane where CFTR resides (P = 0.0002; testing of 155 apical membrane genes jointly and in replication, P = 0.022). These findings suggest that modulating activities of apical membrane constituents could complement current therapeutic paradigms for cystic fibrosis.     

The Eyes Absent proteins in development and disease

The Eyes Absent (EYA) proteins, first described in the context of fly eye development, are now implicated in processes as disparate as organ development, innate immunity, DNA damage repair, photoperiodism, angiogenesis, and cancer metastasis. These functions are associated with an unusual combination of biochemical activities: tyrosine phosphatase and threonine phosphatase activities in separate domains, and transactivation potential when associated with a DNA-binding partner. EYA mutations are linked to multiorgan developmental disorders, as well as to adult diseases ranging from dilated cardiomyopathy to late-onset sensorineural hearing loss. With the growing understanding of EYA biochemical and cellular activity, biological function, and association with disease, comes the possibility that the EYA proteins are amenable to the design of targeted therapeutics. The availability of structural information, direct links to disease states, available animal models, and the fact that they utilize unconventional reaction mechanisms that could allow specificity, suggest that EYAs are well-positioned for drug discovery efforts. This review provides a summary of EYA structure, activity, and function, as they relate to development and disease, with particular emphasis on recent findings.     

Enzymic activation and transfer of fatty acids as acyl-adenylates in mycobacteria

The metabolic repertoire in nature is augmented by generating hybrid metabolites from a limited set of gene products. In mycobacteria, several unique complex lipids are produced by the combined action of fatty acid synthases and polyketide synthases (PKSs), although it is not clear how the covalently sequestered biosynthetic intermediates are transferred from one enzymatic complex to another. Here we show that some of the 36 annotated fadD genes, located adjacent to the PKS genes in the Mycobacterium tuberculosis genome, constitute a new class of long-chain fatty acyl-AMP ligases (FAALs). These proteins activate long-chain fatty acids as acyl-adenylates, which are then transferred to the multifunctional PKSs for further chain extension. This mode of activation and transfer of fatty acids is contrary to the previously described universal mechanism involving the formation of acyl-coenzyme A thioesters. Similar mechanisms may operate in the biosynthesis of other lipid-containing metabolites and could have implications in engineering novel hybrid products.     

Optical properties of amorphous thin film of Se-Te-Ag system prepared by using thermal evaporation technique

Zn_(0.95)Co_(0.05)O and Zn_(0.91)Co_(0.05)Cu_(0.04)O thin films were fabricated on Si(111) substrate by the reactive magnetron sputtering method at different O-Ar ratios.Detailed characterizations by X-ray diffractometry(XRD),X-ray photo-electronic spectrum(XPS), and electron paramagnetic resonance(EPR) indicate that the doped Cu ions substitute the Zn~(2+) ions in the ZnO lattice.The doped Cu ions are in Cu~+ and Cu~(2+) mixture valence states.The ferromagnetism of the Zn_(0.91)Co_(0.05)Cu_(0.04)O film ...     

Photo-induced optical changes in GexAs40Se60-x thin films

Ge-As-Se chalcogenide thin films show a wide range of photosensitivity, which is utilized for the fabrication of micro-optical elements for integrated optics. The photosensitivity of GexAs40Se60?x(x=0,15) chalcogenide thin films for UV light was presented. For that purpose, the bulk samples of GexAs40Se60?x(x=0,15) chalcogenide glasses were prepared using conventional melt quenching technique, and thin films were prepared using thermal evaporation technique. These thin films were exposed to UV light for two hours. Amorphous natures of bulk samples and thin films were verified by XRD and chemical compositions were verified by EDX measurements. The thicknesses of the thin films were measured using a thickness profilometer. Linear optical analysis of these thin films was done using transmission spectra in wavelength range of 300?900 nm. Optical bandgap was determined by first peak of transmission derivative as well as extrapol ation of Tauc’s plot. R2 analysis was done using R software to ensure that the material is indirect bandgap material. It is observed that two hours UV exposure causes photo-darkening along with photo-expansion in As40Se60 thin films, while photo-bleach ing and photo-densification for Ge15As40Se45 thin films. However, the amounts of photo-induced optical changes for Ge15As40Se45 thin films are smaller than those for As40Se60 thin films. The changes in optical absorption, bandgap and thickness are understood base d on the bonding rearrangement caused by UV exposure.     

Synthesis of Novel Nanocomposites of Silica and Guar Gum:Efficient Zinc Ion Binder

1 Results Adsorption using commercial activated carbon (CAC)[1] can remove heavy metals from wastewater[2-4].However,CAC remains an expensive material for heavy metal removal.Ion exchange techniques are also used but it generates volumetric sludge and increases the cost[5].Using naturally occurring seed polysaccharides can solve these problems but their solubility in water limits its application as an adsorbent.Guar gum is a commercially available,industrially important[6-7] polysaccharide material havi...