Background:Some oncogenes such as ERBB2 and EGFR are over-expressed in only a subset of patients. Cancer outlier profile analysis is one of computational approaches to identify outliers in gene expression data. A database with a large sample size would be a great advantage when searching for genes over-expressed in only a subset of patients.Description:GENT (Gene Expression database of Normal and Tumor tissues) is a web-accessible database that provides gene expression patterns across diverse human cancer and normal tissues. More than 40000 samples, profiled by Affymetrix U133A or U133plus2 platforms in many different laboratories across the world, were collected from public resources and combined into two large data sets, helping the identification of cancer outliers that are over-expressed in only a subset of patients. Gene expression patterns in nearly 1000 human cancer cell lines are also provided. In each tissue, users can retrieve gene expression patterns classified by more detailed clinical information.Conclusions:The large samples size (>24300 for U133plus2 and >16400 for U133A) of GENT provides an advantage in identifying cancer outliers. A cancer cell line gene expression database is useful for target validation by in vitro experiment. We hope GENT will be a useful resource for cancer researchers in many stages from target discovery to target validation. GENT is available at http://medicalgenome.kribb.re.kr/GENT/ or http://genome.kobic.re.kr/GENT/.

The myogenic capacity of myoblasts decreases in skeletal muscle with age. In addition to environmental factors, intrinsic factors are important for maintaining the regenerative potential of muscle progenitor cells, but their identities are largely unknown. Here, comparative analysis of microRNA (miRNA) expression profiles in young and old myoblasts uncovered miR-431 as a novel miRNA showing markedly reduced abundance in aged myoblasts. Importantly, elevating miR-431 improved the myogenic capacity of old myoblasts, while inhibiting endogenous miR-431 lowered myogenesis. Bioinformatic and biochemical analyses revealed that miR-431 directly interacted with the 3 ′ untranslated region (UTR) of Smad4 mRNA, which encodes one of the downstream effectors of TGF-β signaling. In keeping with the low levels of miR-431 in old myoblasts, SMAD4 levels increased in this myoblast population. Interestingly, in an in vivo model of muscle regeneration following cardiotoxin injury, ectopic miR-431 injection greatly improved muscle regeneration and reduced SMAD4 levels. Consistent with the finding that the mouse miR-431 seed sequence in the Smad4 3 ′ UTR is conserved in the human SMAD4 3 ′ UTR, inhibition of miR-431 also repressed the myogenic capacity of human skeletal myoblasts. Taken together, our results suggest that the age-associated miR-431 plays a key role in maintaining the myogenic ability of skeletal muscle with age.

Extensive research efforts have been devoted to the development of hydrogel microfibers for tissue engineering, because the vascular structure is related to the transport of nutrients and oxygen as well as the control of metabolic and mechanical functions in the human body. Even though stimuli-responsive properties would enhance the potential applicability of hydrogel microfibers for artificial tissue architectures, previous studies of their fabrication have not considered changes in the microfibers in response to external stimuli. In this work, we prepared temperature-responsive poly(N-isopropylacrylamide) (PNIPAm) microfibers with controlled shapes and sizes by the in situ photo-polymerization of aqueous monomers loaded in calcium alginate templates generated from microcapillary devices. We found that the shape and size of the hydrogel microfibers could be controlled by adjusting the injection positions of the solutions and varying the diameters of the inner capillary, respectively. We further fabricated light-responsive materials by incorporating photothermal magnetite nanoparticles (MNPs) within the temperature-responsive PNIPAm hydrogel microfibers. Because the MNPs incorporated into the PNIPAm microfibers generated heat upon the absorption of visible light, we could demonstrate volume changes in the microfibers triggered by both visible light irradiation and temperature.

This paper presents a system for treating of the actual measured data for load histories. The approach consists of two steps: stress analysis and fatigue damage prediction. Finite element analysis is conducted for the component in question to obtain detailed stress-strain responses. A significant number of failures occurred in a brake end beam which led to economic losses and disruption of service. The cracks appeared to be fatigue cracks caused by the dynamic load produced in the loaded bogie frame. Strain gauge data were analyzed, and fatigue cycles were calculated from this data. Rainflow cycle counting was used to estimate cumulative damage of the end beam under in-service loading conditions. The fatigue life calculated with the rainflow cycle counting method, the P-S-N curve, and the modified Miner's rule agreed well with actual fatigue life within an error range of 2.7%~31%.

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DNA double-strand breaks (DSBs) are the most severe type of DNA damage and are primarily repaired by non-homologous end joining (NHEJ) and homologous recombination (HR) in the G1 and S/G2 phase, respectively. Although CtBP-interacting protein (CtIP) is crucial in DNA end resection during HR following DSBs, little is known about how CtIP levels increase in an S phase-specific manner. Here, we show that Serpine mRNA binding protein 1 (SERBP1) regulates CtIP expression at the translational level in S phase. In response to camptothecin-mediated DNA DSBs, CHK1 and RPA2 phosphorylation, which are hallmarks of HR activation, was abrogated in SERBP1-depleted cells. We identified CtIP mRNA as a binding target of SERBP1 using RNA immunoprecipitation-coupled RNA sequencing, and confirmed SERBP1 binding to CtIP mRNA in S phase. SERBP1 depletion resulted in reduction of polysome-associated CtIP mRNA and concomitant loss of CtIP expression in S phase. These effects were reversed by reconstituting cells with wild-type SERBP1, but not by SERBP1 ΔRGG, an RNA binding defective mutant, suggesting regulation of CtIP translation by SERBP1 association with CtIP mRNA. These results indicate that SERBP1 affects HR-mediated DNA repair in response to DNA DSBs by regulation of CtIP translation in S phase.

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