bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of an innovative inpatient patient navigator program on length of stay and 30‐day readmission
Authors: Kwan Janice L. , Morgan Matthew W. , Stewart Thomas E. , Bell Chaim M. 
Published: August 2015

BACKGROUNDThe current climate of increasing patient complexity coupled with rising costs have prompted the need for adaptive innovation. There are limited data describing inpatient interventions targeting improvements in both communication and transitional care.OBJECTIVEEvaluate the patient navigator (PN) program, an innovative inpatient intervention intended to enhance navigation through the complexity of hospital admissions for patients and providers.INTERVENTIONPNs were dedicated patient‐care facilitators without clinical responsibilities integrated as full members of the inpatient care team responsible for enhancing communication between and among patients and providers.DESIGNObservational retrospective cohort study.PATIENTSAll patients admitted to the general medical service between July 2010 and March 2014.SETTINGAcademic medical center.MEASUREMENTSPrimary outcomes were hospital length of stay (LOS) and 30‐day readmission rate matched by case mix group, age category, and resource intensity weight.RESULTSOur matched cohort included 5628 admissions (4592 patients) exposed and 2213 admissions (1920 patients) not exposed to PNs. Admissions with PNs were 1.3 days (21%) shorter than admission without PNs (6.2 vs 7.5 days, P < 0.001). Thirty‐day readmission rate was not different between the 2 groups (13.1 vs 13.8%, P = 0.48).CONCLUSIONImplementation of this intervention was associated with a reduction in LOS without an increase in 30‐day readmission. Journal of Hospital Medicine 2015;10:799–803. © 2015 Society of Hospital Medicine
Evaluation of genetic association of neurodevelopment and neuroimmunological genes with antipsychotic treatment response in schizophrenia in Indian populations
Authors: Jajodia Ajay , Kaur Harpreet , Kumari Kalpana , Kanojia Neha , Gupta Meenal , Baghel Ruchi , Sood Mamta , Jain Sanjeev , Chadda Rakesh K. , Kukreti Ritushree 
Published: August 2015

AbstractNeurodevelopmental and neuroimmunological genes critically regulate antipsychotic treatment outcome. We report genetic associations of antipsychotic response in 742 schizophrenia patients from Indian populations of Indo‐European and Dravidian ancestry, segregated by disease severity. Meta‐analysis comparing the two populations identified CCL2 [rs4795893: OR (95% CI) = 1.79 (1.27–2.52), P = 7.62 × 10−4; rs4586: OR (95% CI) = 1.74 (1.24–2.43), P = 1.13 × 10−3] and GRIA4 [rs2513265: OR (95% CI) = 0.53 (0.36–0.78), P = 1.44 × 10−3] in low severity group; and, ADCY2 [rs1544938: OR (95% CI) = 0.36 (0.19–0.65), P = 7.68 × 10−4] and NRG1 [rs13250975, OR (95% CI) = 0.42 (0.23–0.79), P = 6.81 × 10−3; rs17716295, OR (95% CI) = 1.78 (1.15–2.75), P = 8.71 × 10−3] in high severity group, with incomplete response toward antipsychotics. To our knowledge, this is the first study to identify genetic polymorphisms associated with the efficacy of antipsychotic treatment of schizophrenia patients from two major India populations.
MicroRNA regulation of viral immunity, latency, and carcinogenesis of selected tumor viruses and HIV
Authors: Wang Ling , Li Guangyu , Yao Zhi Q. , Moorman Jonathan P. , Ning Shunbin 
Published: August 2015

SummaryMicroRNAs (miRNAs) function as key regulators in immune responses and cancer development. In the contexts of infection with oncogenic viruses, miRNAs are engaged in viral persistence, latency establishment and maintenance, and oncogenesis. In this review, we summarize the potential roles and mechanisms of viral and cellular miRNAs in the host–pathogen interactions during infection with selected tumor viruses and HIV, which include (i) repressing viral replication and facilitating latency establishment by targeting viral transcripts, (ii) evading innate and adaptive immune responses via toll‐like receptors, RIG‐I‐like receptors, T‐cell receptor, and B‐cell receptor pathways by targeting signaling molecules such as TRAF6, IRAK1, IKKε, and MyD88, as well as downstream targets including regulatory cytokines such as tumor necrosis factor α, interferon γ, interleukin 10, and transforming growth factor β, (iii) antagonizing intrinsic and extrinsic apoptosis pathways by targeting pro‐apoptotic or anti‐apoptotic gene transcripts such as the Bcl‐2 family and caspase‐3, (iv) modulating cell proliferation and survival through regulation of the Wnt, PI3K/Akt, Erk/MAPK, and Jak/STAT signaling pathways, as well as the signaling pathways triggered by viral oncoproteins such as Epstein–Barr Virus LMP1, by targeting Wnt‐inhibiting factor 1, SHIP, pTEN, and SOCSs, and (v) regulating cell cycle progression by targeting cell cycle inhibitors such as p21/WAF1 and p27/KIP1. Further elucidation of the interaction between miRNAs and these key biological events will facilitate our understanding of the pathogenesis of viral latency and oncogenesis and may lead to the identification of miRNAs as novel targets for developing new therapeutic or preventive interventions. Copyright © 2015 John Wiley & Sons, Ltd.
Short term exendin‐4 treatment reduces markers of metabolic disorders in female offspring of obese rat dams
Authors: Chan Yik Lung , Saad Sonia , Simar David , Oliver Brian , McGrath Kristine , van Reyk David , Bertrand Paul P , Gorrie Cathy , Pollock Carol , Chen Hui 
Published: August 2015

AbstractObjectivesMaternal obesity imposes significant health risks in the offspring including diabetes and dyslipidemia. We previously showed that the hypoglycaemic agent exendin‐4 (Ex‐4) administered from weaning can reverse the maternal impact of ‘transmitted disorders’ in such offspring. However daily injection for six‐weeks was required and the beneficial effect may lapse upon drug withdrawal. This study aimed to investigate whether short term Ex‐4 treatment during suckling period in a rodent model can reverse transmitted metabolic disorders due to maternal obesity.MethodsMaternal obesity was induced in female Sprague Dawley rats by high‐fat diet feeding for 6 weeks, throughout gestation and lactation. Female offspring were treated with Ex‐4 (5 μg/kg/day) between postnatal day (P) 4 and 14. Female offspring were harvested at weaning (P20). Lipid and glucose metabolic markers were measured in the liver and fat. Appetite regulators were measured in the plasma and hypothalamus.ResultsMaternal obesity significantly increased body weight, fat mass, and liver weight in the offspring. There was an associated inhibition of peroxisomal proliferator activated receptor gamma coactivator 1α (PGC1α), increased fatty acid synthase (FASN) expression in the liver, and reduced adipocyte triglyceride lipase (ATGL) expression. It also increased the plasma gut hormone ghrelin and reduced glucagon‐like peptide‐1. Ex‐4 treatment partially reversed the maternal impact on adiposity and impaired lipid metabolism in the offspring, with increased liver PGC1α and inhibition of FASN mRNA expression. Ex‐4 treatment also increased the expression of a novel fat depletion gene a2‐zinc‐glycoprotein 1 in the fat tissue.ConclusionShort term Ex‐4 treatment during the suckling period significantly improved the metabolic profile in the offspring from the obese mothers at weaning. Long‐term studies are needed to follow such offspring to adulthood to examine the sustained effects of Ex‐4 in preventing the development of metabolic disease.
Networks, trust and capital mobilisation: challenges of embedded local entrepreneurial strategies in Ghana's oil and gas industry
Authors: Ablo Austin Dziwornu , Overå Ragnhild 
Published: August 2015

ABSTRACTIn December 2010 Ghana pumped its first oil and a local content law was passed in 2013 to promote local participation in the oil and gas industry. This paper examines Ghanaian entrepreneurial activities and the dynamics of local participation in the emerging oil and gas sector. We explore Ghanaian entrepreneurs' strategies of mobilising networks to acquire information, build trust, raise financial capital and reduce risk with the aim to gain entry, win contracts and participate in the oil and gas industry. We argue that the resources and strategies activated by entrepreneurs embedded in the context of the Ghanaian business environment are inadequate and problematic when deployed in the context of the international oil and gas industry. The international oil companies' cost-intensive standard requirements and state officials' informal interventions further limit local firms' prospects for participation in the oil and gas industry.
PARP14 promotes the Warburg effect in hepatocellular carcinoma by inhibiting JNK1-dependent PKM2 phosphorylation and activation
Authors: Iansante Valeria , Choy Pui Man , Fung Sze Wai , Liu Ying , Chai Jian-Guo , Dyson Julian , Del Rio Alberto , D’Santos Clive , Williams Roger , Chokshi Shilpa , Anders Robert A , Bubici Concetta , Papa Salvatore 
Published: August 2015

AbstractMost tumour cells use aerobic glycolysis (the Warburg effect) to support anabolic growth and evade apoptosis. Intriguingly, the molecular mechanisms that link the Warburg effect with the suppression of apoptosis are not well understood. In this study, using loss-of-function studies in vitro and in vivo, we show that the anti-apoptotic protein poly(ADP-ribose) polymerase (PARP)14 promotes aerobic glycolysis in human hepatocellular carcinoma (HCC) by maintaining low activity of the pyruvate kinase M2 isoform (PKM2), a key regulator of the Warburg effect. Notably, PARP14 is highly expressed in HCC primary tumours and associated with poor patient prognosis. Mechanistically, PARP14 inhibits the pro-apoptotic kinase JNK1, which results in the activation of PKM2 through phosphorylation of Thr365. Moreover, targeting PARP14 enhances the sensitization of HCC cells to anti-HCC agents. Our findings indicate that the PARP14-JNK1-PKM2 regulatory axis is an important determinant for the Warburg effect in tumour cells and provide a mechanistic link between apoptosis and metabolism.
Direct oriented growth of armchair graphene nanoribbons on germanium
Authors: Jacobberger Robert M. , Kiraly Brian , Fortin-Deschenes Matthieu , Levesque Pierre L. , McElhinny Kyle M. , Brady Gerald J. , Rojas Delgado Richard , Singha Roy Susmit , Mannix Andrew , Lagally Max G. , Evans Paul G. , Desjardins Patrick , Martel Richard , Hersam Mark C. , Guisinger Nathan P. , Arnold Michael S. 
Published: August 2015

AbstractGraphene can be transformed from a semimetal into a semiconductor if it is confined into nanoribbons narrower than 10 nm with controlled crystallographic orientation and well-defined armchair edges. However, the scalable synthesis of nanoribbons with this precision directly on insulating or semiconducting substrates has not been possible. Here we demonstrate the synthesis of graphene nanoribbons on Ge(001) via chemical vapour deposition. The nanoribbons are self-aligning 3° from the Ge〈110〉 directions, are self-defining with predominantly smooth armchair edges, and have tunable width to <10 nm and aspect ratio to >70. In order to realize highly anisotropic ribbons, it is critical to operate in a regime in which the growth rate in the width direction is especially slow, <5 nm h−1. This directional and anisotropic growth enables nanoribbon fabrication directly on conventional semiconductor wafer platforms and, therefore, promises to allow the integration of nanoribbons into future hybrid integrated circuits.
Effects of the properties of short peptides conjugated with cell-penetrating peptides on their internalization into cells
Authors: Matsumoto Ryo , Okochi Mina , Shimizu Kazunori , Kanie Kei , Kato Ryuji , Honda Hiroyuki 
Published: August 2015

AbstractPeptides, especially intracellular functional peptides that can play a particular role inside a cell, have attracted attention as promising materials to control cell fate. However, hydrophilic materials like peptides are difficult for cells to internalize. Therefore, the screening and design of intracellular functional peptides are more difficult than that of extracellular ones. An effective high-throughput screening system for intracellular functional peptides has not been reported. Here, we demonstrate a novel peptide array system for screening intracellular functional peptides, in which both cell-penetrating peptide (CPP) domain and photo-cleavable linkers are used. By using this screening system, we determined how the cellular uptake properties of CPP-conjugated peptides varied depending on the properties of the conjugated peptides. We found that the internalization ability of CPP-conjugated peptides varied greatly depending on the property of the conjugated peptides and anionic peptides drastically decreased the uptake ability. We summarized our data in a scatter diagram that plots hydrophobicity versus isoelectric point (pI) of conjugated peptides. These results define a peptide library suitable for screening of intracellular functional peptides. Thus, our system, including the diagram, is a promising tool for searching biological active molecules such as peptide-based drugs.
Unsaturated fatty acids enhance cell yields and perturb the energy metabolism of an antibody-secreting hybridoma
Authors: BUTLER Michael , HUZEL Norman , BARNABÉ Norman 
Published: August 2015

Growth of the murine B-lymphocyte cell line CC9C10 and the myeloma SP2/0 was enhanced significantly by the presence of the unsaturated fatty acids, oleic and linoleic acids in serum-free culture. The cellular content of linoleic and oleic acids gradually increased during continuous culture passage, with no evidence of regulatory control. Over 10 culture passages in the presence of these fatty acids, the unsaturated/saturated fatty acid ratio of all cellular lipid fractions increased substantially. Most of the fatty acid accumulated in the polar lipid fraction (more than 74%) and only a small proportion was oxidized to CO2 (0.5%).
Linoleic acid caused a decrease to one-eighth in the rate of metabolism of glutamine and a 1.4-fold increase in the rate of metabolism of glucose. There was no change in the relative flux of glucose through the pathways of glycolysis, pentose phosphate or the tricarboxylic acid cycle. The changes in energy metabolism were reversed when the cells were removed from fatty acid-supplemented medium. The most plausible explanation for these effects is the observed decrease in the rate of uptake of glutamine into cells loaded with linoleic acid. Growth of the CC9C10 cells in linoleic acid caused the Km of glutamine uptake to increase from 2.7 to 23 mM, whereas glucose uptake was unaffected.
Endogenous basic fibroblast growth factor isoforms involved in different intracellular protein complexes
Authors: PATRY Véronique , BUGLER Béatrix , MARET Arlette , POTIER Michel , PRATS Hervé 
Published: August 2015

Four forms of basic fibroblast growth factor (bFGF or FGF-2) result from an alternative initiation of translation involving one AUG (155-amino acid form) and three CUGs (210-, 201- and 196-amino acid forms). These different forms of bFGF show different intracellular biological activities. To identify their intracellular targets, the 210- and 155-amino acid forms of bFGF were independently transfected into CHO cells and their correct subcellular localizations were verified, the 155-amino acid bFGF form being essentially cytoplasmic whereas the 210-amino acid protein was nuclear. The radiation fragmentation method was used to determine the target size of the different bFGF isoforms in the transfected CHO cells and to show that the 210- and 155-amino acids bFGF isoforms were included in protein complexes of 320 and 130 kDa respectively. Similar results were obtained using the SK-Hep1 cell line, which naturally expressed all forms of bFGF. Co-immunoprecipitation assays using different chimaeric bFGF–chloramphenicol acetyltransferase proteins showed that different cellular proteins are associated with different parts of the bFGF molecule. We conclude that bFGF isoforms are involved in different molecular complexes in the cytosol and nucleus, which would reflect different functions for these proteins.
Mucins secreted by a transformed cell line derived from human tracheal gland cells
Authors: LO-GUIDICE Jean-Marc , MERTEN Marc D. , LAMBLIN Geneviève , PORCHET Nicole , HOUVENAGHEL Marie-Christine , FIGARELLA Catherine , ROUSSEL Philippe , PERINI Jean-Marc 
Published: August 2015

High-molecular-mass glycoconjugates are secreted by the continuous cell line MM-39, which has been obtained from cultured human tracheal gland cells transformed by simian virus 40. They were purified on Sepharose® CL-4B and then by two steps of density-gradient centrifugation. High-molecular-mass glycoproteins resistant to digestion by hyaluronidase, chondroitin ABC lyase and heparitinase were obtained, in addition to hyaluronic acid and proteoglycans. They were susceptible to β-elimination. They contained polylactosaminoglycan chains as well as carbohydrate chains with a terminal sialic acid in the NeuAc α2-3 sequence. Most of them have a buoyant density of 1.45 g/ml in CsCl-density-gradient centrifugation, except for MUC1. The MM-39 cells were also characterized by a high expression of MUC1 and MUC4 genes, but they did not express MUC2, MUC3, MUC5B and MUC5AC. Therefore the MM-39 cells synthesized mucin-like glycoproteins as well as lysozyme and mucous proteinase inhibitor [Merten, Kammouni, Renaud, Birg, Mattéi and Figarella (1996) Am. J. Respir. Cell. Mol. Biol. 15, 520–528]; they should be considered as having a mixed, both serous and mucous, phenotype.
Novel 30 kDa protein possessing ATP-binding and chaperone activities
Authors: ITOH Hideaki , TASHIMA Yohtalou 
Published: August 2015

A 30 kDa protein was purified from pig liver cytosol by using ATP-Sepharose and Green A column chromatography. The partial amino acid sequences of the protein (95 amino acid residues) had no similarity with any proteins recorded in data banks. The protein was able to form a stable complex with unfolded dihydrofolate reductase (DHFR). The spontaneous refolding of chemically denatured DHFR was arrested by the 30 kDa protein. This inhibition presumably results from the formation of a stable complex between the 30 kDa protein and DHFR. Bound DHFR could be released from the protein with ATP. The protein also showed protease resistance in an ATP-dependent manner. Incubation of the 30 kDa protein with 5 mM ATP resulted in its resistance to V8 protease or to trypsin treated with 1-chloro-4-phenyl-3-L-toluene-p-sulphonamidobutan-2-one. Divalent cations enhanced the ATP-protection effect. CD analysis of the 30 kDa protein showed that ATP induced an increase in the β-pleated sheet content and a decrease in the α-helix content of the 30 kDa protein. These results suggest that the 30 kDa protein, a novel cytosolic protein, might have an affinity for ATP, a chaperonin activity, and and an ATP-protection effect against some proteases in vivo.
Removal of hydrogen peroxide by the 29 kDa protein of Entamoeba histolytica
Authors: BRUCHHAUS Iris , RICHTER Symi , TANNICH Egbert 
Published: August 2015

The 29 kDa protein of Entamoeba histolytica (Eh29), as well as a truncated variant of this protein, which lacks a cysteine-rich N-terminal region of 40 amino acid residues (Eh29mut), were recombinantly expressed in Escherichia coli and purified to homogeneity. Both recombinant proteins (recEh29, recEh29mut) were found to have hydrogen peroxide (H2O2)-removing activity, but recEh29 was twice as active as recEh29mut. For the consumption of exogenous H2O2, activity was dependent on the presence of reducing equivalents, such as dithiothreitol (DTT), indicating that Eh29 constitutes a thiol-dependent peroxidase. DTT was not required to remove H2O2 by recEh29 or recEh29mut when H2O2 was generated enzymically by the E. histolytica NADPH:flavin oxidoreductase. This enzyme produces H2O2 under aerobic conditions and simultaneously serves as a hydrogen donor for Eh29. Peroxidase activity of the recombinant proteins was further supported by complementation of an E. coli strain that lacks the entire alkyl hydroperoxide reductase locus. The high sensitivity of these bacteria against cumene hydroperoxide was significantly reduced by the introduction of the genes encoding recEh29 or recEh29mut. Using antisera raised against the recombinant proteins, native Eh29 was localized within the cytoplasm of the amoebae. In addition, the antisera reacted with proteins of E. histolytica lysates with apparent molecular masses of 35 kDa and 160–300 kDa. All of them exhibited thiol-peroxidase activity.
Evidence that human class Theta glutathione S-transferase T1-1 can catalyse the activation of dichloromethane, a liver and lung carcinogen in the mouse: Comparison of the tissue distribution of GST T1-1 with that of classes Alpha, Mu and Pi GST in human
Authors: SHERRATT Philip J. , PULFORD David J. , HARRISON David J. , GREEN Trevor , HAYES John D. 
Published: August 2015

The cDNA encoding human glutathione S-transferase (GST) T1 has been expressed as two recombinant forms in Escherichia coli that could be purified by affinity chromatography on either IgG-Sepharose or nickel-agarose; one form of the transferase was synthesized from the pALP 1 expression vector as a Staphylococcus aureus protein A fusion, whereas the other form was synthesized from the pET-20b expression vector as a C-terminal polyhistidine-tagged recombinant. The yields of the two purified recombinant proteins from E. coli cultures were approx. 15 mg/l for the protein A fusion and 25 mg/l for the C-terminal polyhistidine-tagged GST T1-1. The purified recombinant proteins were catalytically active, although the protein A fusion was typically only 5–30% as active as the histidine-tagged GST. Both recombinant forms could catalyse the conjugation of glutathione with the model substrates 1,2-epoxy-3-(4′-nitrophenoxy)propane, 4-nitrobenzyl chloride and 4-nitrophenethyl bromide but were inactive towards 1-chloro-2,4-dinitrobenzene, ethacrynic acid and 1-menaphthyl sulphate. Recombinant human GST T1-1 was found to exhibit glutathione peroxidase activity and could catalyse the reduction of cumene hydroperoxide. In addition, recombinant human GST T1-1 was found to conjugate glutathione with dichloromethane, a pulmonary and hepatic carcinogen in the mouse. Immunoblotting with antibodies raised against different transferase isoenzymes showed that GST T1-1 is expressed in a large number of human organs in a tissue-specific fashion that differs from the pattern of expression of classes Alpha, Mu and Pi GST. Most significantly, GST T1-1 was found in only low levels in human pulmonary soluble extract of cells, suggesting that in man the lung has little capacity to activate the volatile dichloromethane.