bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of exercise and insulin on SREBP-1c expression in human skeletal muscle: potential roles for the ERK1/2 and Akt signalling pathways
Authors: Boonsong T. , Norton L. , Chokkalingam K. , Jewell K. , Macdonald I. , Bennett A. , Tsintzas K. 
Published: November 2007

SREBP-1c (sterol-regulatory-element-binding protein 1c) is a transcription factor that regulates genes associated with glucose and fatty acid metabolism and exhibits responsiveness to insulin and exercise. We have examined the effects of exercise on basal and insulin-mediated changes in the activation (phosphorylation) of the signalling molecules involved in the regulation of SREBP-1c and related them to changes in the expression of SREBP-1c in human skeletal muscle. Eight healthy men performed one-legged cycling for 90 min; 24 h later a hyperinsulinaemic euglycaemic clamp for 4 h was performed. Muscle biopsies were obtained from the rested (control) leg and the exercised leg immediately after exercise and before and after the insulin clamp. Immediately after exercise, phosphorylation of ERK (extracellular-signal-regulated kinase) 1, ERK2 and Akt (protein kinase B) was higher in the exercised than the control leg. SREBP-1c mRNA content was not affected by exercise, whereas its protein level was lower in the exercised than the control leg and returned to pre-exercise levels 24 h later. Similarly, SREBP-1c mRNA content was ∼1.5-fold higher in the exercised than the control leg 24 h after exercise. Insulin infusion up-regulated SREBP-1c mRNA level ∼2-fold, but did not affect its protein level. Phosphorylation of Akt also increased in response to insulin clamp, whereas phospho-ERK1 and -ERK2 levels were unchanged. Neither exercise nor insulin affected STAT3 (signal transducer and activator of transcription 3) or p38 MAPK (mitogen-activated protein kinase) phosphorylation. These findings suggest that exercise-induced changes in muscle SREBP-1c expression might be mediated by the activation of the ERK1/2 pathway, whereas Akt might be a positive regulator of SREBP-1c in human skeletal muscle under insulin-stimulated conditions.
mVps34 is activated by an acute bout of resistance exercise
Authors: MacKenzie M.G. , Hamilton D.L. , Murray J.T. , Baar K. 
Published: November 2007

Resistance-exercise training results in a progressive increase in muscle mass and force production. Following an acute bout of resistance exercise, the rate of protein synthesis increases proportionally with the increase in protein degradation, correlating at 3 h in the starved state. Amino acids taken immediately before or immediately after exercise increase the post-exercise rate of protein synthesis. Therefore a protein that controls protein degradation and amino acid-sensitivity would be a potential candidate for controlling the activation of protein synthesis following resistance exercise. One such candidate is the class III PI3K (phosphoinositide 3-kinase) Vps34 (vacuolar protein sorting mutant 34). Vps34 controls both autophagy and amino acid signalling to mTOR (mammalian target of rapamycin) and its downstream target p70 S6K1 (S6 kinase 1). We have identified a significant increase in mVps34 (mammalian Vps34) activity 3 h after resistance exercise, continuing for at least 6 h, and propose a mechanism whereby mVps34 could act as an internal amino acid sensor to mTOR after resistance exercise.
Towards new tuberculosis drugs
Authors: Cole S.T. , Alzari P.M. 
Published: November 2007

The need for better drugs to treat tuberculosis has never been greater. Despite insufficient funding for discovery research, intensive efforts have been made to find and develop new lead compounds capable of reducing the duration of the present treatment known as DOTS (directly observed therapy short course), from 6 to under 4 months. This minireview describes the progress achieved during the last 5 years and highlights some of the successes without neglecting the problems.
Characterization of cancer stem cells in chronic myeloid leukaemia
Authors: Jørgensen H.G. , Holyoake T.L. 
Published: November 2007

CML (chronic myeloid leukaemia) is a myeloproliferative disease that originates in an HSC (haemopoietic stem cell) as a result of the t(9;22) translocation, giving rise to the Ph (Philadelphia chromosome) and bcr-abl oncoprotein. The disease starts in CP (chronic phase), but as a result of genomic instability, it progresses over time to accelerated phase and then to BC (blast crisis), becoming increasingly resistant to therapy. bcr-abl is a constitutively active tyrosine kinase that has been targeted by TKIs (tyrosine kinase inhibitors), including IM (imatinib mesylate), nilotinib and dasatinib. We have developed various flow cytometry techniques to enable us to isolate candidate CML stem cells from CP patients at diagnosis that efflux Hoechst dye, express CD34, lack CD38 and are cytokine-non-responsive in culture over periods of up to 12 days in growth factors. These stem cells have been shown to regenerate bcr-abl-positive haemopoiesis in immunocompromised mice upon transplantation. We previously demonstrated that IM was antiproliferative for CML stem cells but did not induce apoptosis. Clinical experience now confirms that IM may not target CML stem cells in vivo with few patients achieving complete molecular remission and relapse occurring rapidly upon drug withdrawal. Our recent efforts have focused on understanding why CML stem cells are resistant to IM and on trying to find novel ways to induce apoptosis of this population. We have shown that CML stem cells express very high levels of functional wild-type bcr-abl; no kinase domain mutations have been detected in the stem cell population. Dasatinib, a more potent multitargeted TKI than IM, inhibits bcr-abl activity more efficiently than IM but still does not induce apoptosis of the stem cell population. Most recently, we have tested a number of novel drug combinations and found that FTIs (farnesyl transferase inhibitors) have activity against CML. BMS-214662 is the most effective of these and induces apoptosis of phenotypically and functionally defined CML stem cells in vitro, as a single agent and in combination with IM or dasatinib. The effect against CML stem cells is selective with little effect on normal stem cells. The drug is also effective against BC CML stem cells and equally effective against wild-type and mutant bcr-abl, including the most resistant mutant T315I. In association with apoptosis, there is activation of caspase 8 and caspase 3, inhibition of the MAPK pathway, IAP-1 (inhibitor of apoptosis protein-1), NF-κB (nuclear factor κB) and iNOS (inducible nitric oxide synthase). Furthermore, BMS-214662 synergizes with MEK1/2 [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase 1/2] inhibitors, suggesting a second mechanism other that RAS inhibition for induction of apoptosis. Our intentions are now to explore the activity of BMS-214662 in other cancer stem cell disorders and to move this preclinical work to a clinical trial combining dasatinib with BMS-214662 in CML.
Combination of indomethacin and statin compared with indomethacin and placebo in patients with a first episode of acute pericarditis: preliminary findings
Authors: Di Pasquale Pietro , Cannizzaro Sergio , Fasullo Sergio , Ganci Filippo , Marenghini Giorgio , Scalzo Sebastiano , Giambanco Francesco , Vitale Giuseppe , Polizzi Giovanni , Paterna Salvatore 
Published: November 2007

The aim of the present study was to evaluate the safety and efficacy of the combination of indomethacin and statin compared with indomethacin plus placebo in patients with a first episode of pericarditis. A total of 55 consecutive patients with acute pericarditis were randomized in a double-blind manner into two groups: group 1 (statin group) was treated with 150 mg of indomethacin plus 10 mg of rosuvastatin, and group 2 (placebo group) was treated with 150 mg of indomethacin plus placebo. Both groups received treatment up to the normalization of inflammation markers and for the following week. Clinical and laboratory assessments [white cell count, ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein), troponin I, creatine kinase and brain natriuretic peptide plasma levels], ECG and echocardiogram were performed at baseline and daily up to discharge. All of the patients were followed as outpatients for 3 months to evaluate any recurrence of pericarditis. The two groups were similar in age, sex and laboratory parameters [group 1 (the statin group), n=28 patients; gender, 18 male and ten female; and age, 29.5±5.7 years; group 2 (placebo group), n=27 patients; gender, 16 male/11 female; and age, 29.2±4.8 years]. The statin group, when compared with the placebo group, had a significantly faster reduction in CRP values (5.0±1.0 compared with 6.0±2.0 days respectively; P=0.022), ST segment normalization (3.5±1.0 compared with 4.5±1.0 days respectively; P=0.001), pericardial effusion (4.5±1.0 compared with 5.5±1.0 days respectively; P=0.001) and ESR (5.0±1 compared with 6.0±2 days respectively; P=0.022). Our results show that the combination of statin and indomethacin treatment in patients with acute pericarditis is feasible, with a significant reduction in inflammatory markers and a favourable trend in hospitalization time (5.5±2.0 compared with 6.5±2.0 days respectively; P=0.069). However, these preliminary findings require further studies in a larger sample of patients.
Reduced body mass index is associated with increased angiotensin II in young women with postural tachycardia syndrome
Authors: Stewart Julian M. , Taneja Indu , Medow Marvin S. 
Published: November 2007

Altered peripheral haemodynamics, decreased cardiac output, decreased blood volume and increased AngII (angiotensin II) have been reported in POTS (postural tachycardia syndrome). Recent findings indicate that BMI (body mass index) may be reduced. In the present study, we investigated the hypothesis that reduced BMI is associated with haemodynamic abnormalities in POTS and that this is related to AngII. We studied 52 patients with POTS, aged 14–29 years, compared with 36 control subjects, aged 14–27 years. BMI was not significantly reduced on average in the POTS patients, but was reduced in patients with decreased peripheral blood flow. POTS patients were then subdivided on the basis of BMI, and supine haemodynamics were measured. There was no difference in blood volume or cardiac output once BMI or body mass were accounted for. When POTS patients with BMI &lt;50th percentile were compared with controls, calf blood flow [1.63±0.31 compared with 3.58±0.67 ml−1·min−1·(100 ml of tissue)−1] and maximum venous capacity (3.87±0.32 compared with 4.98±0.36 ml/100 ml of tissue) were decreased, whereas arterial resistance [56±0.5 compared with 30±4 mmHg·ml−1·min−1·(100 ml of tissue)−1] and venous resistance [1.23±0.17 compared with 0.79±0.11 mmHg·ml−1·min−1·(100 ml of tissue)−1] were increased. Similar findings were also observed when POTS patients with BMI &lt;50th percentile were compared with POTS patients with BMI &gt;50th percentile. There was no relationship between blood flow, resistance or maximum venous capacity with BMI in control subjects. BMI was inversely related to plasma AngII concentrations in those POTS patients with decreased peripheral blood flow, consistent with cachectic properties of the octapeptide. Patients with low-flow POTS had decreased body mass, but decreased body mass alone cannot account for findings of peripheral vasoconstriction. In conclusion, the findings suggest that reduced body mass relates to increased plasma AngII.
Moment invariants as shape recognition technique for comparing protein binding sites
Authors: Sommer Ingolf , Müller Oliver , Domingues Francisco S. , Sander Oliver , Weickert Joachim , Lengauer Thomas 
Published: November 2007

AbstractMotivation: An approach for identifying similarities of protein–protein binding sites is presented. The geometric shape of a binding site is described by computing a feature vector based on moment invariants. In order to search for similarities, feature vectors of binding sites are compared. Similar feature vectors indicate binding sites with similar shapes.Results: The approach is validated on a representative set of protein–protein binding sites, extracted from the SCOPPI database. When querying binding sites from a representative set, we search for known similarities among 2819 binding sites. A median area under the ROC curve of 0.98 is observed. For half of the queries, a similar binding site is identified among the first two of 2819 when sorting all binding sites according the proposed similarity measure. Typical examples identified by this method are analyzed and discussed. The nitrogenase iron protein-like SCOP family is clustered hierarchically according to the proposed similarity measure as a case study.Availability: Python code is available on request from the authors.Contact: sommer@mpi-inf.mpg.deSupplementary information: Supplementary data are available at Bioinformatics online.
CONSORF: a consensus prediction system for prokaryotic coding sequences
Authors: Kang Sungsoo , Yang Sung-Jin , Kim Sangsoo , Bhak Jong 
Published: November 2007

AbstractSummary: CONSORF is a fully automatic high-accuracy identification system that provides consensus prokaryotic CDS information. It first predicts the CDSs supported by consensus alignments. The alignments are derived from multiple genome-to-proteome comparisons with other prokaryotes using the FASTX program. Then, it fills the empty genomic regions with the CDSs supported by consensus ab initio predictions. From those consensus results, CONSORF provides prediction reliability scores, predicted frame-shifts, alternative start sites and best pair-wise match information against other prokaryotes. These results are easily accessed from a website.Availability: The regularly updated CDS predictions of prokaryotic genomes as well as the source code are freely accessible through http://consorf.kobic.re.kr and http://orfome.org.Contact: j@bio.cc, jong@kribb.re.kr or sskimb@ssu.ac.krSupplementary information: The detailed methods and evaluation results can be found at http://consorf.kobic.re.kr/supplementary/.
NPIDB: a Database of Nucleic Acids–Protein Interactions
Authors: Spirin Sergei , Titov Mikhail , Karyagina Anna , Alexeevski Andrei 
Published: November 2007

AbstractSummary: The database NPIDB (Nucleic Acids—Protein Interaction DataBase) contains information derived from structures of DNA–protein and RNA–protein complexes extracted from PDB (1834 complexes in July 2007). It is organized as a collection of files in PDB format and is equipped with a web-interface and a set of tools for extracting biologically meaningful characteristics of complexes. The content of the database is weekly updated.Availability: http://monkey.belozersky.msu.ru/NPIDB/Contact: sas@belozersky.msu.ru
PfamAlyzer: domain-centric homology search
Authors: Hollich Volker , Sonnhammer Erik L.L. 
Published: November 2007

AbstractSummary: PfamAlyzer is a Java applet that enables exploration of Pfam domain architectures using a user-friendly graphical interface. It can search the UniProt protein database for a domain pattern. Domain patterns similar to the query are presented graphically by PfamAlyzer either in a ranked list or pinned to the tree of life. Such domain-centric homology search can assist identification of distant homologs with shared domain architecture.Availability: PfamAlyzer has been integrated with the Pfam database and can be accessed at http://pfam.cgb.ki.se/pfamalyzer.Contact: Erik.Sonnhammer@ki.se
Aggregata octopiana (Protista: Apicomplexa): a dangerous pathogen during commercial Octopus vulgaris ongrowing
Authors: Gestal Camino , Guerra Angel , Pascual Santiago 
Published: November 2007

AbstractGestal, C., Guerra, A., and Pascual, S. 2007. Aggregata octopiana (Protista: Apicomplexa): a dangerous pathogen during commercial Octopus vulgaris ongrowing. – ICES Journal of Marine Science, 64. The haemolymph parameters for Octopus vulgaris and the condition index at molecular level were analysed using RNA/DNA and RNA/protein ratios on animals reared in floating cage systems and naturally infected by the coccidian Aggregata octopiana. Statistical analysis showed that as A. octopiana infection increased, there was a decrease in most inorganic elements and/or in haemocyte concentrations in cellular and/or plasma fractions. Also, the protein concentrations in the haemolymph plasma fraction dropped significantly as the coccidian infection increased. Results suggest that the severity of the infection by A. octopiana is a limiting factor during commercial ongrowing of the common octopus, at least in floating cage systems. Control measurements are needed in aquaculture to avoid this environmental stressor.
Preparation and Use of Microcolumns for Sample Desalting or Nanoscale IMAC
Authors: Steen Hanno , Stensballe Allan , Jensen Ole N. 
Published: November 2007

INTRODUCTIONIn this method, microcolumns are prepared using any kind of chromatographic resin. The resin is held in place by making a constriction at the end of a GELoader pipette tip. Sample loading, washing, and elution are performed by loading liquid on top of the resin and applying air pressure to generate a low flow through the column. No frits are necessary.
Preparation of Immobilized Enzyme Microcolumns: Figure 1.
Authors: Larsen Martin R. 
Published: November 2007

INTRODUCTIONPeptide mapping by MALDI-TOF-MS has emerged as a powerful proteomics tool for identifying and characterizing proteins. One of the key steps in this method involves the proteolytic cleavage of proteins, followed by MS analysis of the generated peptides. A limitation of the method, especially for high-throughput proteomics, is the speed and efficiency of proteolytic cleavage. In this protocol, a method for rapid tryptic digestion using immobilized enzyme microcolumns is described.
Analysis of Phosphopeptides by μLC-ESI-MS/MS
Authors: Corthals Garry L. , Wasinger Valerie C. , Goodlett David R. 
Published: November 2007

INTRODUCTIONWhether using a pressure cell or gel-loader tips, IMAC-purified peptides can be injected into a μLC separation system and analyzed by μLC-ESI-MS/MS. Phosphopeptides behave and elute similarly to nonphosphorylated peptides during RP-HPLC, but because of a decrease in hydrophobicity due to the addition of the phosphate moiety, a phosphopeptide will generally elute before the nonphosphopeptide with the identical amino acid sequence. This difference in elution time is most pronounced for short peptides. Thus, when analyzing phosphopeptides from μLC online with ESI-MS/MS, it is prudent to acquire data during the wash step (i.e., prior to gradient elution), as some short phosphopeptides may not even bind to the C18 resin in 100% aqueous solutions. Otherwise, these very hydrophilic peptides will be missed. This protocol provides typical μLC conditions for the separation of IMAC-enriched phosphopeptides when the μLC system is online with the ESI-MS/MS.
Dewaxing and Rehydrating Sections prior to In Situ Hybridization
Authors: Nagy Andras , Gertsenstein Marina , Vintersten Kristina , Behringer Richard 
Published: November 2007

INTRODUCTIONThis protocol describes how to remove wax from embryo or tissue sections that have been affixed to glass slides. Traditionally, xylene has been used for this purpose, but less toxic solutions can also be employed. The embryo or tissue sections are then progressively rehydrated for compatibility with subsequent alcohol stains, aqueous stains, immunohistochemistry, or in situ hybridization.
Imaging Real-Time Gene Expression in Mammalian Cells with Single-Transcript Resolution: Figure 1.
Authors: Wells Amber L. , Condeelis John S. , Singer Robert H. , Zenklusen Daniel 
Published: November 2007

INTRODUCTIONThe MS2 system provides optimal sensitivity for single-molecule detection in cells. It requires two genetically encoded moieties: a reporter mRNA that contains MS2 binding site (MBS) stem loops and a fluorescent MS2 coat protein (MCP-xFP) that binds to the stem loops with high affinity, thus tagging the mRNA within the cell. This protocol describes transfection of COS-7 cells with reporter RNA (e.g., pRSV-Z-24 MBS-β-actin) and MCP-xFP (e.g., pPolII-MCP-GFP-NLS) plasmids using calcium phosphate precipitation. The reporter mRNA plasmid must be co-transfected with the MCP-xFP-NLS plasmid for simultaneous expression in a cell. The unbound MCP-xFP-NLS is sequestered in the nucleus, leaving only the MCP-xFP-NLS that is bound to the reporter mRNA in the cytoplasm. This provides a high signal-to-noise ratio (SNR) that permits detection of single mRNA molecules. The Delta T Imaging System is used for image acquisition of fluorescent particles in the cells.
Imaging Real-Time Gene Expression in Living Systems with Single-Transcript Resolution: Single mRNA Particle Tracking with ImageJ-Based Analysis
Authors: Wells Amber L. , Condeelis John S. , Singer Robert H. , Zenklusen Daniel 
Published: November 2007

INTRODUCTIONThis protocol describes the use of ImageJ software (freely available from NIH) to analyze particle dynamics in a cell using time-lapse movie frames or image stacks of fluorescent mRNA particles. Maximum intensity projections and kymographs are produced.
Fate-Mapping Technique: Grafting Fluorescent Cells into Gastrula-Stage Mouse Embryos at 7-7.5 Days Post-coitum
Authors: Franklin Vanessa J. , Bildsoe Heidi , Tam Patrick P.L. 
Published: November 2007

INTRODUCTIONAnalysis of the developmental fate of cell populations in different parts of the embryo enables the construction of fate maps. These reveal the organization of the body plan and can presage the expression of molecular characteristics of cell lineages and the formation of body parts. The efficacy of fate-mapping techniques is critically dependent on their ability to track the cells and all their descendants without compromising the development of the embryo. Cell grafting involves isolating a population of genetically tagged cells from a transgenic embryo and grafting them to a defined site in a nontransgenic host embryo. Tissue colonization is analyzed using a genetic tag (e.g., a fluorescent protein that can be visualized noninvasively) that allows tracking of the transplanted cells and their descendants in the host embryo throughout development in culture. Alternatively, a lacZ transgene can be used to localize graft-derived cells histologically. Differentiation of the graft-derived cells can be studied by examining the expression of molecular markers by in situ hybridization of gene transcripts or immunohistochemical detection of lineage-specific proteins. This protocol describes how to graft cells isolated from a donor embryo into the germ layer of a wild-type host mouse embryo at 7-7.5 days post-coitum (dpc).