A comprehensive functional analysis of tissue specificity of human gene expression

<p>Abstract</p> <p>Background</p> <p>In recent years, the maturation of microarray technology has allowed the genome-wide analysis of gene expression patterns to identify tissue-specific and ubiquitously expressed ('housekeeping') genes. We have performed a functional and topological analysis of housekeeping and tissue-specific networks to identify universally necessary biological processes, and those unique to or characteristic of particular tissues.</p> <p>Results</p> <p>We measured whole genome expression in 31 human tissues, identifying 2374 housekeeping genes expressed in all tissues, and genes uniquely expressed in each tissue. Comprehensive functional analysis showed that the housekeeping set is substantially larger than previously thought, and is enriched with vital processes such as oxidative phosphorylation, ubiquitin-dependent proteolysis, translation and energy metabolism. Network topology of the housekeeping network was characterized by higher connectivity and shorter paths between the proteins than the global network. Ontology enrichment scoring and network topology of tissue-specific genes were consistent with each tissue's function and expression patterns clustered together in accordance with tissue origin. Tissue-specific genes were twice as likely as housekeeping genes to be drug targets, allowing the identification of tissue 'signature networks' that will facilitate the discovery of new therapeutic targets and biomarkers of tissue-targeted diseases.</p> <p>Conclusion</p> <p>A comprehensive functional analysis of housekeeping and tissue-specific genes showed that the biological function of housekeeping and tissue-specific genes was consistent with tissue origin. Network analysis revealed that tissue-specific networks have distinct network properties related to each tissue's function. Tissue 'signature networks' promise to be a rich source of targets and biomarkers for disease treatment and diagnosis.</p

Formation of Amyloid-Like Fibrils by Y-Box Binding Protein 1 (YB-1) Is Mediated by Its Cold Shock Domain and Modulated by Disordered Terminal Domains

YB-1, a multifunctional DNA- and RNA-binding nucleocytoplasmic protein, is involved in the majority of DNA- and mRNA-dependent events in the cell. It consists of three structurally different domains: its central cold shock domain has the structure of a β-barrel, while the flanking domains are predicted to be intrinsically disordered. Recently, we showed that YB-1 is capable of forming elongated fibrils under high ionic strength conditions. Here we report that it is the cold shock domain that is responsible for formation of YB-1 fibrils, while the terminal domains differentially modulate this process depending on salt conditions. We demonstrate that YB-1 fibrils have amyloid-like features, including affinity for specific dyes and a typical X-ray diffraction pattern, and that in contrast to most of amyloids, they disassemble under nearly physiological conditions

All-fiber mode-locked laser at 977 nm

In this paper, we have developed Yb-doped fiber suitable for creation of all-fiber seed laser schemes operating near 977 nm. The fiber was based on a ring-doping design (cladding was partially doped with Yb-ions), which allowed us to fabricate a relatively small core and provide mode field diameter (MFD) of the active fiber comparable with standard fibers (to achieve small splicing losses with commercially available optical fibers) and, simultaneously, increase absorption from the cladding to keep a reasonably high lasing efficiency. So MFDx of the fiber was 12 μm, MFDy was 14 μm. Outer silica cladding of the active fiber was decreased to diameter of 80 μm and a special pump and signal combiner was used to inject pump and signal into the active fiber. Based on the developed Yb-doped fiber an all-fiber polarization maintaining mode-locked laser with central wavelength around 977 nm was demonstrated for the first time. SESAM was used as a saturable absorber. The laser was self-starting for pump powers above 4.6 W, with the output power of 3 mW. The autocorrelation was the best fitted with sech2 profile and pulse duration was estimated to be as long as 9.5 ps. The fundamental cavity frequency corresponded to the pulse repetition rate of 33.532 MHz. Signal-to-noise ratio measured in the radio frequency range was more than 50 dB, the line width was below 1 kHz, which indicate ultimate stability of the fabricated mode-lock laser.acceptedVersionPeer reviewe

The domain organization of YB-1.

<p>(A), Prediction of structured and intrinsically disordered regions of YB-1 by IsUnstruct algorithm. Disorder is assigned to score values greater than or equal to 0.5. CSD is highlighted by gray shading. (B), The tertiary structure of CSD and sketched terminal domains. (C), YB-1 and its fragments used in the study. The indicated regions belong to different YB-1 domains.</p

Fibril formation by YB-1 and its fragments.

<p>Protein samples (10 µM) were incubated in the presence of 2 M LiCl for 24 h. Supramolecular complex formation was visualized by EM (left) and AFM (right) imaging. (A), YB-1; (B), YB-1_1–219; (C), YB-1_1–129; (D), YB-1_52–129. Scale bars are 0.4 µm where not indicated.</p