Genome-wide analysis of mammalian DNA segment fusion/fission

As a powerful tool for gene function prediction, gene fusion has been widely studied in prokaryotes and certain groups of eukaryotes, but it has been little applied in studies of mammalian genomes. With the first fully sequenced mammalian genomes (human, mouse, rat) now available, we defined and collected a set of fusion/fission event-linked segments (FFLS) based on structured organized genomic alignment. The statistics of the sequence features highlighted the FFLSs against their random context. We found that there are three groups of FFLSs with different component pairs (i.e. gene-gene, gene-noncoding and noncoding-noncoding) in all three mammalian genomes. The proteins encoded by the components of FFLSs in the first group shown a strong tendency to interact with each other. The segmental components in the last two groups which did not contain any protein-coding genes, were found not only to be transcribed to some level, but also more conserved than the random background. Thus, these segments are possibly carrying certain biologically functional elements. We propose that FFLS may be a potential tool for prediction and analysis of function and functional interaction of genetic elements, including both genes and noncoding elements, in mammalian genomes. The full list of the FFLSs in the genomes of the three mammals is available as supporting information at doi:10.1016/j.jtbi.2005.09.016.     

High Performance Flexible Supercapacitor Electrodes Composed of Ultralarge Graphene Sheets and Vanadium Dioxide

Little is known regarding the effect of the graphene lateral size on the electrochemical performance of hybrid graphene electrode. This work examines the electrochemical performance of a flexible hybrid supercapacitor electrode composed of ultralarge graphene oxide (UGO; mean lateral size of 47 ± 22 μm) and vanadium dioxide (VO₂) nanobelts, referring to a reference electrode composed of small scale graphene oxide (SGO; mean lateral size of 0.8 ± 0.5 μm) and VO₂.Thermal treatment converts UGO/VO₂ and SGO/VO₂ to URGO/VO₂ (denoted VURGO) and SRGO/VO₂ (denoted VSRGO) electrodes, respectively. The sheet resistance of the VURGO film (0.57 ± 0.03 kΩ sq.^–1) was two orders of magnitude lower than that of the VSRGO (55.74 ± 9.35 kΩ sq.^–1). The VURGO hybrid electrode showed a specific capacitance of 769 F g^?1, which was significantly better than the corresponding values for the VSRGO electrode (385 F/g). These results support the notion that the use of ultralarge graphene sheets (≈22 500 μm²) lowers the intersheet resistance due to the presence of fewer intersheet tunneling barriers. This article highlights the potential utility of URGO (as a conductive support) in hybrid electrode containing VO₂ nanobelts for high performance flexible hybrid supercapacitor.     

Oxysterol-binding protein (OSBP) enhances replication of intracellular Salmonella and binds the Salmonella SPI-2 effector SseL via its N-terminus

Effectors translocated into the host cell by Salmonella enterica serovar Typhimurium are critical for bacterial virulence. For many effectors, the mechanisms of their interactions with host pathways are not yet understood. We have recently found an interaction between the SPI-2 effector SseL and oxysterol-binding protein (OSBP). We show here that SseL binds the N-terminus of OSBP and that S. Typhimurium infection results in redistribution of OSBP. We furthermore demonstrate that OSBP is required for efficient replication of intracellular S. Typhimurium. This suggests that S. Typhimurium hijacks OSBP-dependent pathways to benefit its intracellular life-style, possibly by SseL- and OSBP-mediated manipulation of host lipid metabolism.     

TIE-2/VEGF-R2 SAR and in vitro activity of C3-acyl dihydroindazolo[5,4-a]pyrrolo[3,4-c]carbazole analogs

Orally bioavailable, dual inhibitors of TIE-2/VEGF-R2 were identified by elaborating the C3/N13 SAR around a fused pyrrolodihydroindazolocarbazole scaffold. Analogs bearing a C3-thiophencarbonyl group were evaluated in enzymatic and cellular biochemical assays; two orally bioavailable analogs were further profiled in functional assays and found to inhibit microvessel growth in rat aortic explant cultures and inhibit Ang-1-stimulated chemotaxis of HUVECs.     

Heptad repeats regulate protein phosphatase 2a recruitment to I-kappaB kinase gamma/NF-kappaB essential modulator and are targeted by human T-lymphotropic virus type 1 tax

The switching on-and-off of I-kappaB kinase (IKK) and NF-kappaB occurs rapidly after signaling. How activated IKK becomes down-regulated is not well understood. Here we show that following tumor necrosis factor-alpha stimulation, protein phosphatase 2A (PP2A) association with IKK is increased. A heptad repeat in IKKgamma, helix 2 (HLX2), mediates PP2A recruitment. Two other heptad repeats downstream of HLX2, termed coiled-coil region 2 (CCR2) and leucine zipper (LZ), bind HLX2 and negatively regulate HLX2 interaction with PP2A. HTLV-1 transactivator Tax also binds HLX2, and this interaction is enhanced by CCR2 but reduced by LZ. In the presence of Tax, PP2A-IKKgamma binding is greatly strengthened. Interestingly, peptides spanning CCR2 and/or LZ disrupt IKKgamma-Tax and IKKgamma-PP2A interactions and potently inhibit NF-kappaB activation by Tax and tumor necrosis factor-alpha. We propose that when IKK is resting, HLX2, CCR2, and LZ form a helical bundle in which HLX2 is sequestered. The HLX2-CCR2-LZ bundle becomes unfolded by signal-induced modifications of IKKgamma or after Tax binding. In this conformation, IKK becomes activated. IKKgamma then recruits PP2A via the exposed HLX2 domain for rapid down-regulation of IKK. Tax-PP2A interaction, however, renders PP2A inactive, thus maintaining Tax-PP2A-IKK in an active state. Finally, CCR2 and LZ possibly inhibit IKK activation by stabilizing the HLX2-CCR2-LZ bundle.     

Peptide microarray analysis of substrate specificity of the transmembrane Ser/Thr kinase KPI-2 reveals reactivity with cystic fibrosis transmembrane conductance regulator and phosphorylase

Human lemur (Lmr) kinases are predicted to be Tyr kinases based on sequences and are related to neurotrophin receptor Trk kinases. This study used homogeneous recombinant KPI-2 (Lmr2, LMTK2, Cprk, brain-enriched protein kinase) kinase domain and a library of 1,154 peptides on a microarray to analyze substrate specificity. We found that KPI-2 is strictly a Ser/Thr kinase that reacts with Ser either preceded by or followed by Pro residues but unlike other Pro-directed kinases does not strictly require an adjacent Pro residue. The most reactive peptide in the library corresponds to Ser-737 of cystic fibrosis transmembrane conductance regulator, and the recombinant R domain of cystic fibrosis transmembrane conductance regulator was a preferred substrate. Furthermore the KPI-2 kinase phosphorylated peptides corresponding to the single site in phosphorylase and purified phosphorylase b, making this only the second known phosphorylase b kinase. Phosphorylase was used as a specific substrate to show that KPI-2 is inhibited in living cells by addition of nerve growth factor or serum. The results demonstrate the utility of the peptide library to probe specificity and discover kinase substrates and offer a specific assay that reveals hormonal regulation of the activity of this unusual transmembrane kinase.     

Extraction and Separation of Sinapine from Rapeseed Cake and the Mode of Action of Melanin Production Inhibition

Molecular Biology - Brassica campestris L. is the important oil-bearing crop in China. Rapeseed cake is the main byproduct of rapeseed oil extraction. As the main active ingredient in rapeseed...     

Differential effects of circadian typology on sleep-related symptoms,physical fatigue and psychological well-being in relation to resilience

Various physiological and psychological functions are influenced by circadian typology (CT), which was reported to be related to resilience. However, few studies have assessed the effects of CT in relation to resilience. The aim of the present study was to assess the influence of CT on sleep-related symptoms, physical fatigue and psychological well-being in relation to resilience. The present study included a total of 1794 healthy hospital employees, and they completed the Morningness–Eveningness Questionnaire, Connor–Davidson Resilience Scale, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Fatigue Severity Scale, Hospital Anxiety and Depression Scale and World Health Organization Quality of Life Scale Abbreviated Version. Subjects with evening type showed lower sleep quality, more daytime sleepiness and physical fatigue than neither types and morning types. Additionally, evening types were more depressed and anxious and reported a poorer quality of life. CT was found to be a significant predictor of sleep quality, but CT was minimally associated with physical fatigue and psychological well-being in the regression analysis. Instead, resilience was substantially related to all of the variables measured. In conclusion, CT independently predicts sleep quality, but the effects of CT on physical fatigue and psychological well-being are negligible compared to those of resilience.