BISC: Binary SubComplexes in proteins database

Binary subcomplexes in proteins database (BISC) is a new protein–protein interaction (PPI) database linking up the two communities most active in their characterization: structural biology and functional genomics researchers. The BISC resource offers users (i) a structural perspective and related information about binary subcomplexes (i.e. physical direct interactions between proteins) that are either structurally characterized or modellable entries in the main functional genomics PPI databases BioGRID, IntAct and HPRD; (ii) selected web services to further investigate the validity of postulated PPI by inspection of their hypothetical modelled interfaces. Among other uses we envision that this resource can help identify possible false positive PPI in current database records. BISC is freely available at http://bisc.cse.ucsc.edu

SP701-A-Growing and Harvesting Switchgrass for Ethanol Production in Tennessee

Switchgrass is a warm-season perennial grass native to North America. The plant can reach heights up to 10 feet with an extensive root system. Once established, switchgrass well-managed for biomass should have a productive life of 10-20 years. Within the stand, switchgrass is an extremely strong competitor. However, it is not considered an invasive plant. Switchgrass adapts well to a variety of soil and climatic conditions. It is most productive on moderately well to well-drained soils of medium fertility and a soil pH at 5.0 or above. The high cellulosic content of switchgrass makes it a favorable feedstock for ethanol production. It is anticipated that switchgrass can yield sufficient biomass to produce approximately 500 gallons of ethanol per acre. While the Tennessee Biofuels Initiative includes a demonstration plant to make ethanol from switchgrass, the market for switchgrass as an energy crop remains limited. Producers will likely need to be located within 30 to 50 miles of a cellulosic ethanol plant. Producing switchgrass for energy generally occurs under some form of contractual arrangement with the end-user. To reap potential benefits from using switchgrass for cellulosic ethanol production, the system of production must be profitable for farmers and energy producers, as well as cost effective for consumers

LKB1/AMPK and PKA Control ABCB11 Trafficking and Polarization in Hepatocytes.

Polarization of hepatocytes is manifested by bile canalicular network formation and activation of LKB1 and AMPK, which control cellular energy metabolism. The bile acid, taurocholate, also regulates development of the canalicular network through activation of AMPK. In the present study, we used collagen sandwich hepatocyte cultures from control and liver-specific LKB1 knockout mice to examine the role of LKB1 in trafficking of ABCB11, the canalicular bile acid transporter. In polarized hepatocytes, ABCB11 traffics from Golgi to the apical plasma membrane and endogenously cycles through the rab 11a-myosin Vb recycling endosomal system. LKB1 knockout mice were jaundiced, lost weight and manifested impaired bile canalicular formation and intracellular trafficking of ABCB11, and died within three weeks. Using live cell imaging, fluorescence recovery after photobleaching (FRAP), particle tracking, and biochemistry, we found that LKB1 activity is required for microtubule-dependent trafficking of ABCB11 to the canalicular membrane. In control hepatocytes, ABCB11 trafficking was accelerated by taurocholate and cAMP; however, in LKB1 knockout hepatocytes, ABCB11 trafficking to the apical membrane was greatly reduced and restored only by cAMP, but not taurocholate. cAMP acted through a PKA-mediated pathway which did not activate AMPK. Our studies establish a regulatory role for LKB1 in ABCB11 trafficking to the canalicular membrane, hepatocyte polarization, and canalicular network formation

A qualitative stakeholder analysis of avian influenza policy in Bangladesh

Avian influenza is a major animal and public health concern in Bangladesh. A decade after development and implementation of the first national avian influenza and human pandemic influenza preparedness and response plan in Bangladesh, a two-stage qualitative stakeholder analysis was performed in relation to the policy development process and the actual policy. This study specifically aimed to identify the future policy options to prevent and control avian influenza and other poultry-related zoonotic diseases in Bangladesh. It was recommended that the policy should be based on the One Health concept, be evidence-based, sustainable, reviewed and updated as necessary. The future policy environment that is suitable for developing and implementing these policies should take into account the following points: the need to formally engage multiple sectors, the need for clear and acceptable leadership, roles and responsibilities, and the need for a common pool of resources and provision for transferring resources. Most of these recommendations are directed towards the Government of Bangladesh. However, other sectors, including research and poultry production stakeholders, also have a major role to play to inform policy-making and actively participate in the multi-sectoral approach

Antioxidant and Antitumor Activity of a Bioactive Polyphenolic Fraction Isolated from the Brewing Process

There is increasing interest in identifying natural bioactive compounds that can improve mitochondrial functionality and regulate apoptosis. The brewery industry generates wastewater that could yield a natural extract containing bioactive phenolic compounds. Polyphenols act as antioxidants and have been documented to protect the human body from degenerative diseases such as cardiovascular diseases or cancer. The main aims of our research were to determine the phenolic profile of a crude extract obtained (at pilot scale) from a brewery waste stream and to evaluate the biochemical activity of this extract on the mitochondrial function of a cancer cell line (SH-SY5Y). This work is a basic translational pilot study. The total phenolic content was determined by the Folin-Ciocalteu assay, which revealed that 2.30% of the extract consisted of phenolic compounds. The polyphenols, identified and quantified by reverse-phase-high-performance liquid chromatography and mass spectrometry (RP-HPLC/MS), were mainly flavonoids. After cell culture, the tumoral cells treated with the polyphenolic extract showed enhanced mitochondrial oxidative function, which is likely related to a decrease in oxidative stress and an increase in mitochondrial biogenesis. This type of brewery waste stream, properly treated, may be a promising source of natural antioxidants to replace the synthetic antioxidants currently used in the food industry

Long-latency modulation of motor cortex excitability by ipsilateral posterior inferior frontal gyrus and pre-supplementary motor area

The primary motor cortex (M1) is strongly influenced by several frontal regions. Dual-site transcranial magnetic stimulation (dsTMS) has highlighted the timing of early (<40 ms) prefrontal/premotor influences over M1. Here we used dsTMS to investigate, for the first time, longer-latency causal interactions of the posterior inferior frontal gyrus (pIFG) and pre-supplementary motor area (pre-SMA) with M1 at rest. A suprathreshold test stimulus (TS) was applied over M1 producing a motor-evoked potential (MEP) in the relaxed hand. Either a subthreshold or a suprathreshold conditioning stimulus (CS) was administered over ipsilateral pIFG/pre-SMA sites before the TS at different CS-TS inter-stimulus intervals (ISIs: 40-150 ms). Independently of intensity, CS over pIFG and pre-SMA (but not over a control site) inhibited MEPs at an ISI of 40 ms. The CS over pIFG produced a second peak of inhibition at an ISI of 150 ms. Additionally, facilitatory modulations were found at an ISI of 60 ms, with supra-but not subthreshold CS intensities. These findings suggest differential modulatory roles of pIFG and pre-SMA in M1 excitability. In particular, the pIFG-but not the pre-SMA-exerts intensity-dependent modulatory influences over M1 within the explored time window of 40-150 ms, evidencing fine-tuned control of M1 output

LKB1 is required for hepatic bile acid transport and canalicular membrane integrity in mice

LKB1 is a ‘master’ protein kinase implicated in the regulation of metabolism, cell proliferation, cell polarity and tumorigenesis. However, the long-term role of LKB1 in hepatic function is unknown. In the present study, it is shown that hepatic LKB1 plays a key role in liver cellular architecture and metabolism. We report that liver-specific deletion of LKB1 in mice leads to defective canaliculi and bile duct formation, causing impaired bile acid clearance and subsequent accumulation of bile acids in serum and liver. Concomitant with this, it was found that the majority of BSEP (bile salt export pump) was retained in intracellular pools rather than localized to the canalicular membrane in hepatocytes from LLKB1KO (liver-specific Lkb1-knockout) mice. Together, these changes resulted in toxic accumulation of bile salts, reduced liver function and failure to thrive. Additionally, circulating LDL (low-density lipoprotein)-cholesterol and non-esterified cholesterol levels were increased in LLKB1KO mice with an associated alteration in red blood cell morphology and development of hyperbilirubinaemia. These results indicate that LKB1 plays a critical role in bile acid homoeostasis and that lack of LKB1 in the liver results in cholestasis. These findings indicate a novel key role for LKB1 in the development of hepatic morphology and membrane targeting of canalicular proteins

Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A>G Variant Is Determinant of Increased Atorvastatin Response

Aims: The relationship between variants in SLCO1B1 and SLCO2B1 genes and lipid-lowering response to atorvastatin was investigated. Material and Methods: One-hundred-thirty-six unrelated individuals with hypercholesterolemia were selected and treated with atorvastatin (10 mg/day/4 weeks). They were genotyped with a panel of ancestry informative markers for individual African component of ancestry (ACA) estimation by SNaPshot® and SLCO1B1 (c.388A&gt;G, c.463C&gt;A and c.521T&gt;C) and SLCO2B1 (−71T&gt;C) gene polymorphisms were identified by TaqMan® Real-time PCR. Results: Subjects carrying SLCO1B1 c.388GG genotype exhibited significantly high low-density lipoprotein (LDL) cholesterol reduction relative to c.388AA+c.388AG carriers (41 vs. 37%, p = 0.034). Haplotype analysis revealed that homozygous of SLCO1B1*15 (c.521C and c.388G) variant had similar response to statin relative to heterozygous and non-carriers. A multivariate logistic regression analysis confirmed that c.388GG genotype was associated with higher LDL cholesterol reduction in the study population (OR: 3.2, CI95%:1.3–8.0, p &lt; 0.05). Conclusion: SLCO1B1 c.388A&gt;G polymorphism causes significant increase in atorvastatin response and may be an important marker for predicting efficacy of lipid-lowering therapy

Inter- versus intramodal integration in sensorimotor synchronization: a combined behavioral and magnetoencephalographic study

Although the temporal occurrence of the pacing signal is predictable in sensorimotor synchronization tasks, normal subjects perform on-the-beat-tapping to an isochronous auditory metronome with an anticipatory error. This error originates from an intermodal task, that is, subjects have to bring information from the auditory and tactile modality to coincide. The aim of the present study was to illuminate whether the synchronization error is a finding specific to an intermodal timing task and whether the underlying cortical mechanisms are modality-specific or supramodal. We collected behavioral data and cortical evoked responses by magneto-encephalography (MEG) during performance of cross- and unimodal tapping-tasks. As expected, subjects showed negative asynchrony in performing an auditorily paced tapping task. However, no asynchrony emerged during tactile pacing, neither during pacing at the opposite finger nor at the toe. Analysis of cortical signals resulted in a three dipole model best explaining tap-contingent activity in all three conditions. The temporal behavior of the sources was similar between the conditions and, thus, modality independent. The localization of the two earlier activated sources was modality-independent as well whereas location of the third source varied with modality. In the auditory pacing condition it was localized in contralateral primary somatosensory cortex, during tactile pacing it was localized in contralateral posterior parietal cortex. In previous studies with auditory pacing the functional role of this third source was contradictory: A special temporal coupling pattern argued for involvement of the source in evaluating the temporal distance between tap and click whereas subsequent data gave no evidence for such an interpretation. Present data shed new light on this question by demonstrating differences between modalities in the localization of the third source with similar temporal behavior