bluuebunny/crossref_metadata_2025_split huggingface dataset:
Candidate tumour suppressor CCDC19 regulates miR‐184 direct targeting of C‐Myc thereby suppressing cell growth in non‐small cell lung cancers
Authors: Liu Zhen , Mai Chunping , Yang Huiling , Zhen Yan , Yu Xiaoli , Hua Shengni , Wu Qiangyun , Jiang Qinping , Zhang Yajie , Song Xin , Fang Weiyi 
Published: June 2014

AbstractWe previously reported and revised the nasopharyngeal epithelium specific protein CCDC19 and identified it as a potential tumour suppressor in nasopharyngeal carcinoma. The purpose of this study was to investigate the involvement of CCDC19 in the pathogenesis of human non‐small cell lung cancers (NSCLC). Down‐regulated CCDC19 expression was observed in NSCLC tissues and cells compared to normal tissues. However, reduced protein expression did not correlate with the status of NSCLC progression. Instead, we observed that patients with lower CCDC19 expression had a shorter overall survival than did patients with higher CCDC19 expression. Lentiviral‐mediated CCDC19 overexpression significantly suppressed cell proliferation and cell cycle transition from G1 to S and G2 phases in NSCLC cells. Knocking down CCDC19 expression significantly restored the ability of cell growth in CCDC19 overexpressing NSCLC cells. Mechanistically CCDC19 functions as a potential tumour suppressor by stimulating miR‐184 suppression of C‐Myc thus blocking cell growth mediated by the PI3K/AKT/C‐Jun pathway. Our studies are the first to demonstrate that reduced expression of CCDC19 is an unfavourable factor in NSCLC.
ASD, ADHD, mental health conditions and psychopharmacology in neurogenetic syndromes: parent survey
Authors: Reilly C. , Senior J. , Murtagh L. 
Published: June 2014

AbstractBackgroundThere are a number of neurogenetic syndromes with well described behavioural phenotypes including fragile X syndrome, Prader–Willi syndrome, Williams syndrome and velo‐cardio‐facial syndrome (VCFS). Autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and psychiatric conditions are often associated with the syndromes.MethodParents (n = 381) of school‐aged children with one of the four syndromes in the UK and Ireland were asked whether their child had been professionally diagnosed with ASD, ADHD or a mental health condition. Parents were also asked whether their child had been prescribed medication for behavioural or psychiatric reasons.ResultsThe highest level of reported diagnoses of ASD and ADHD was in fragile X syndrome. In all syndrome groups, lower rates of diagnosis were reported in comparison to previously published research. Prescribing of medication for behavioural/psychiatric reasons was highest in fragile X syndrome although the highest usage of melatonin was in Williams syndrome.ConclusionReasons for a lower recognition of ASD, ADHD and mental health conditions in clinical practice compared with research studies may include ‘diagnostic overshadowing’ due to presence of intellectual disability and a genetic syndrome. However, there may also be a lack of belief in the utility of such diagnoses in neurogenetic syndromes among relevant professionals and/or lack of access to professionals with sufficient expertise in the recognition of such diagnoses in those with neurogenetic syndromes. The low rates of prescribing of medication for behavioural/psychiatric reasons may reflect the low level of clinical diagnoses or lack of belief in the utility of psychopharmacology in this population.
Signalling Theory and Equilibrium in Strategic Management Research: An Assessment and a Research Agenda
Authors: Bergh Donald D. , Connelly Brian L. , Ketchen David J. , Shannon Lu M. 
Published: June 2014

AbstractActors within organizations commonly must make choices armed with incomplete and asymmetrically distributed information. Signalling theory seeks to explain how individuals are able to do so. This theory's primary predictive mechanism is ‘separating equilibrium’, which occurs when a signal's expectations are confirmed through experience. A content analysis finds that most strategic management signalling theory studies have not fully leveraged separating equilibrium. This presents two possible paths for future research. First, some researchers may wish to incorporate separating equilibrium. We illustrate how doing so can uncover new relationships, generate novel insights, and fortify the theory's application. Others who want to theorize about signals, but not examine separating equilibrium, could integrate ideas from signalling theory with other information perspectives. Here a signal becomes one stimulus among many that corporate actors interpret and act upon. We provide research agendas so strategy scholars can apply signalling theory most effectively to meet their research objectives.
The chemokine receptors CXCR1 and CXCR2 regulate oral cancer cell behaviour
Authors: Khurram Syed A. , Bingle Lynne , McCabe Brenka M. , Farthing Paula M. , Whawell Simon A. 
Published: June 2014

BackgroundChemokines regulate physiological and pathological leucocyte trafficking, and chemokine receptors play a role in tumorigenesis. Expression of interleukin‐8 (IL‐8) receptors CXCR1 and CXCR2 has been shown in oral squamous cell carcinoma (OSCC) but remains poorly characterised. This aim of this study was to investigate CXCR1 and CXCR2 expression on normal oral keratinocytes (NOKs) and oral cancer cell lines (OCCL) and their relative response when exposed to IL‐8 and growth‐related oncogene‐α (which selectively binds CXCR2).MethodsmRNA and protein expression was studied using RT‐PCR, immunocytochemistry and flow cytometry. ELISAs were used to investigate ERK1/2 phosphorylation and MMP production, whereas a MTS‐based assay was employed to study proliferation. Migration assays were carried out using modified Boyden chambers with a matrigel coating used for invasion assays.ResultsmRNA expression of CXCR1 and CXCR2 was seen in both NOKs and OCCL with significantly higher protein expression in OCCL. Exposure to IL‐8 and GROα increased intracellular ERK phosphorylation, proliferation, migration and invasion with OCCL showing a greater response than NOKs. These effects were mediated through CXCR1 and CXCR2 (for IL‐8) and CXCR2 (for GROα) as receptor‐blocking antibodies significantly inhibited the responses. IL‐8 and GROα also increased MMP‐9 release from NOKs and OCCL with significantly higher amounts released by OCCL. However, an increase in MMP‐7 production was only seen in OCCL.ConclusionsFunctional CXCR1 and CXCR2 exist on normal and cancerous oral epithelial cells, and our data suggests a role for these receptors in oral cancer biology.
Periodontal ligament‐derived cells for periodontal regeneration in animal models: a systematic review
Authors: Bright R. , Hynes K. , Gronthos S. , Bartold P. M. 
Published: June 2014

Background and ObjectiveImplantation of periodontal ligament stem cells is emerging as a potential periodontal regenerative procedure. This systematic review considers the evidence from animal models investigating the use of periodontal ligament stem cells for successful periodontal regeneration.Material and MethodsPubMed, Embase, MEDLINE and Google Scholar were searched to December 2013 for quantitative studies examining the outcome of implanting periodontal ligament stem cells into experimental periodontal defects in animals. Inclusion criteria were: implantation of periodontal ligament stem cells into surgically created periodontal defects for periodontal regeneration; animal models only; source of cells either human or animal; and published in English. We followed the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines.ResultsFrom the literature search, 43 studies met the inclusion criteria. A wide variety of surgical defects were created in four species of animal (dog, rat, pig and sheep). Owing to wide variability in defect type, cell source and cell scaffold, no meta‐analysis was possible. Outcome measures included new bone, new cementum and new connective tissue formation. In 70.5% of the results, statistically significant improvements of these measures was recorded.ConclusionThese results are notable in that they indicate that irrespective of the defect type and animal model used, periodontal ligament stem cell implantation can be expected to result in a beneficial outcome for periodontal regeneration. It is recommended that there is sufficient evidence from preclinical animal studies to warrant moving to human studies to examine the efficacy, safety, feasibility (autologous vs. allogeneic transplantation) and delivery of periodontal ligament stem cells for periodontal regeneration.
Magnesium‐dependent processes are targets of bacterial manganese toxicity
Authors: Hohle Thomas H. , O'Brian Mark R. 
Published: June 2014

SummaryA Bradyrhizobium japonicum mutant defective in the gene encoding the high‐affinity Mn2+ transporter MntH has a severe growth phenotype under manganese limitation. Here, we isolated suppressor mutants of an mntH strain that grew under manganese limitation, and activities of high‐affinity Mn2+ transport and Mn2+‐dependent enzymes were partially rescued. The suppressor strains harbour gain‐of‐function mutations in the gene encoding the Mg2+ channel MgtE. The MgtE variants likely allow Mn2+ entry via loss of a gating mechanism that normally holds the transporter in the closed state when cellular Mg2+ levels are high. Both MgtE‐dependent and MgtE‐independent suppressor phenotypes were recapitulated by magnesium‐limited growth of the mntH strain. Growth studies of wild‐type cells suggest that manganese is toxic to cells when environmental magnesium is low. Moreover, extracellular manganese and magnesium levels were manipulated to inhibit growth without substantially altering the intracellular content of either metal, implying that manganese toxicity depends on its cellular distribution rather than the absolute concentration. Mg2+‐dependent enzyme activities were found to be inhibited or stimulated by Mn2+. We conclude that Mn2+ can occupy Mg2+ binding sites in cells, and suggest that Mg2+‐dependent processes are targets of manganese toxicity.
Slow growth of Mycobacterium tuberculosis at acidic pH is regulated by phoPR and host‐associated carbon sources
Authors: Baker Jacob J. , Johnson Benjamin K. , Abramovitch Robert B. 
Published: June 2014

SummaryDuring pathogenesis, Mycobacterium tuberculosis (Mtb) colonizes environments, such as the macrophage or necrotic granuloma, that are acidic and rich in cholesterol and fatty acids. The goal of this study was to examine how acidic pH and available carbon sources interact to regulate Mtb physiology. Here we report that Mtb growth at acidic pH requires host‐associated carbon sources that function at the intersection of glycolysis and the TCA cycle, such as pyruvate, acetate, oxaloacetate and cholesterol. In contrast, in other tested carbon sources, Mtb fully arrests its growth at acidic pH and establishes a state of non‐replicating persistence. Growth‐arrested Mtb is resuscitated by the addition of pyruvate suggesting that growth arrest is due to a pH‐dependent checkpoint on metabolism. Additionally, we demonstrate that the phoPR two‐component regulatory system is required to slow Mtb growth at acidic pH and functions to maintain redox homeostasis. Transcriptional profiling and functional metabolic studies demonstrate that signals from acidic pH and carbon source are integrated to remodel pathways associated with anaplerotic central metabolism, lipid anabolism and the regeneration of oxidized cofactors. Because phoPR is required for Mtb virulence in animals, we suggest that pH‐driven adaptation may be critical to Mtb pathogenesis.
Antiemesis effect and brain fMRI response of gastric electrical stimulation with different parameters in dogs
Authors: Yu X. , Tu L. , Lei P. , Song J. , Xu H. , Hou X. 
Published: June 2014

AbstractBackgroundThe aims of this study were to investigate the effect of gastric electrical stimulation (GES) with different parameters on emesis induced by apomorphine, and possible center mechanisms by brain functional magnetic resonance imaging (fMRI).MethodsSix dogs implanted with electrodes on gastric serosa were used in this study. Part 1: Apomorphine was injected in the control session and GES sessions. GESs with different parameters were applied in GES session. Gastric slow waves and emesis and behaviors suggestive of nausea were recorded in each session. Part 2: Each dog was anesthetized and given GESs with different parameters or sham stimulation for 15 min after baseline (5 min), respectively. The location of cerebral activation induced by GES was investigated by fMRI.Key ResultsApomorphine induced emesis and behaviors suggestive of nausea, and gastric dysrhythmia. The emesis frequency in control session was 5.5 ± 0.99, and symptoms score was 22.17 ± 1.01. GES with short pulse and long pulse could not improve emesis and symptoms induced by apomorphine. The emesis frequency (4.5 ± 0.76 in short pulse and 6.33 ± 1.05 in long pulse) and symptoms scores had no significant difference compared to control session (each p > 0.05). GES with trains of short pulse reduced emesis time frequency (3.83 ± 0.7, p = 0.042 vs control) and symptoms score (p = 0.037 vs control) obviously. Brain fMRI showed that GES with short pulse and long pulse activated brain stem region, and trains of short pulse made amygdala and occipital lobe activation.Conclusions & InferencesApomorphine induced emesis and gastric dysrhythmia. GES with trains of short pulses relieves emetic responses through activation of amygdala region.
Standardized herbal treatments on functional bowel disorders: moving from putative mechanisms of action to controlled clinical trials
Authors: Cremonini F. 
Published: June 2014

AbstractSymptom relief in functional gastrointestinal disorders (FGID) is frequently sought with complementary and alternative medicine, and various herbal medicine compounds are popular in different parts of the world. Only a few products, however, are standardized and are backed by scientific evidence. This review mainly focuses on mechanistic and clinical data in support of the Japanese traditional compound Rikkunshi‐to (RKT) and of STW‐5. Their effects on gut sensori‐motor function, neurohormonal network, and controlled clinical data in FGID are revised. RKT and STW‐5 appear to possess some degree of gastroprokinetic, visceral analgesic properties, and seem to increase the gastric accommodation response. Controlled trials of RKT and STW‐5 support at least a modest effect on symptoms of functional dyspepsia and irritable bowel syndrome, with low side effects profile. With the widespread use of herbals and the relative paucity of effective pharmacological options for FGID, rigorous studies to further elucidate pharmacological actions and clinical applications of herbal compounds are a priority.
Should the standard dimethyl sulfoxide concentration be reduced? Results of a European Group for Blood and Marrow Transplantation prospective noninterventional study on usage and side effects of dimethyl sulfoxide
Authors: Morris Curly , de Wreede Liesbeth , Scholten Marijke , Brand Ronald , van Biezen Anja , Sureda Anna , Dickmeiss Ebbe , Trneny Marek , Apperley Jane , Chiusolo Patrizia , van Imhoff Gustaaf W. , Lenhoff Stig , Martinelli Giovanni , Hentrich Marcus , Pabst Thomas , Onida Francesco , Quinn Michael , Kroger Nicolaus , de Witte Theo , Ruutu Tapani ,   Chronic Malignancies and Lymphoma Working Parties of the EBMT
Published: June 2014

BackgroundDimethyl sulfoxide (DMSO) is essential for the preservation of liquid nitrogen–frozen stem cells, but is associated with toxicity in the transplant recipient.Study Design and MethodsIn this prospective noninterventional study, we describe the use of DMSO in 64 European Blood and Marrow Transplant Group centers undertaking autologous transplantation on patients with myeloma and lymphoma and analyze side effects after return of DMSO‐preserved stem cells.ResultsWhile the majority of centers continue to use 10% DMSO, a significant proportion either use lower concentrations, mostly 5 or 7.5%, or wash cells before infusion (some for selected patients only). In contrast, the median dose of DMSO given (20 mL) was much less than the upper limit set by the same institutions (70 mL). In an accompanying statistical analysis of side effects noted after return of DMSO‐preserved stem cells, we show that patients in the highest quartile receiving DMSO (mL and mL/kg body weight) had significantly more side effects attributed to DMSO, although this effect was not observed if DMSO was calculated as mL/min. Dividing the myeloma and lymphoma patients each into two equal groups by age we were able to confirm this result in all but young myeloma patients in whom an inversion of the odds ratio was seen, possibly related to the higher dose of melphalan received by young myeloma patients.ConclusionWe suggest better standardization of preservation method with reduced DMSO concentration and attention to the dose of DMSO received by patients could help reduce the toxicity and morbidity of the transplant procedure.
Novel swine model of transfusion‐related acute lung injury
Authors: Okazaki Hitoshi , Ishikawa Osamu , Iijima Takehiko , Kohira Takahiro , Teranishi Mai , Kawasaki Shin , Saito Akira , Mikami Yu , Sugiura Asuka , Hashimoto Shiho , Shimada Eiko , Uchikawa Makoto , Matsuhashi Mika , Tsuno Nelson H. , Tanaka Minoru , Kiyokawa Nobutaka , Fujimoto Junichiro , Nagase Takahide , Tadokoro Kenji , Takahashi Koki 
Published: June 2014

BackgroundTransfusion‐related acute lung injury (TRALI) is a life‐threatening complication of blood transfusion. Antibodies against human leukocyte antigens in donors' plasma are the major causes of TRALI. Several animal models of TRALI have been developed, and the mechanism underlying TRALI development has been extensively investigated using rodent models. Although sheep models of nonimmune TRALI have been developed, large‐animal models of antibody‐mediated TRALI are not yet available.Study Design and MethodsTo develop a swine model of TRALI, male Clawn strain miniature pigs were used. A monoclonal antibody (MoAb) against swine leukocyte antigens (SLAs) Class I (4G8, 0.3 or 1.0 mg/kg body weight [BW]) and a control antibody (1.0 mg/kg BW) were injected into the peripheral vein after priming with or without 1 μg/kg BW lipopolysaccharide (LPS; n = 3 each). Lung injury was assessed using PaO2/FiO2 (P/F) ratio and by chest X‐ray imaging. Histopathologic analysis was also conducted.ResultsLung injury could be induced by injecting 4G8 at an amount of 1.0 mg/kg BW, after LPS. The P/F ratio 90 minutes after the administration of 4G8 significantly decreased (p < 0.05). Bilateral infiltration was shown in chest X‐ray imaging. Lung injury was confirmed by histopathologic analysis.ConclusionLung injury in pigs was successfully induced by anti‐SLA MoAb. Priming with LPS is a prerequisite for inducing lung injury and the amount of the antibody is a critical condition.
Immunogenicity of a Synthetic Vaccine Based on Plasmodium vivax Duffy Binding Protein Region II
Authors: Ntumngia Francis B. , Barnes Samantha J. , McHenry Amy M. , George Miriam T. , Schloegel Jesse , Adams John H. 
Published: June 2014

ABSTRACTMolecules that play a role inPlasmodiummerozoite invasion of host red blood cells represent attractive targets for blood-stage vaccine development against malaria. InPlasmodium vivax, merozoite invasion of reticulocytes is mediated by the Duffy binding protein (DBP), which interacts with its cognate receptor, the Duffy antigen receptor for chemokines, on the surface of reticulocytes. The DBP ligand domain, known as region II (DBPII), contains the critical residues for receptor recognition, making it a prime target for vaccine development against blood-stage vivax malaria. In natural infections, DBP is weakly immunogenic and DBPII allelic variation is associated with strain-specific immunity, which may compromise vaccine efficacy. In a previous study, a synthetic vaccine termed DEKnull that lacked an immunodominant variant epitope in DBPII induced functional antibodies to shared neutralizing epitopes on the native Sal1 allele. Anti-DEKnull antibody titers were lower than anti-Sal1 titers but produced more consistent, strain-transcending anti-DBPII inhibitory responses. In this study, we further characterized the immunogenicity of DEKnull, finding that immunization with recombinant DEKnull produced an immune response comparable to that obtained with native recombinant DBP alleles. Further investigation of DEKnull is necessary to enhance its immunogenicity and broaden its specificity.
Identification of Occult Fusobacterium nucleatum Central Nervous System Infection by Use of PCR-Electrospray Ionization Mass Spectrometry
Authors: Nagalingam Sudha , Lisgaris Michelle , Rodriguez Benigno , Jacobs Michael R. , Lederman Michael , Salata Robert A , Hujer Andrea M. , Muehlenbachs Atis , DeLeon-Carnes Marlene , Farrell John J. , Sampath Rangarajan , Bonomo Robert A. 
Published: June 2014

ABSTRACT

Anaerobic bacteria are often difficult to detect, especially after the initiation of antibiotics. We describe the application of PCR-electrospray ionization mass spectrometry (PCR/ESI-MS) using a sample of cerebrospinal fluid to identify an anaerobic Gram-negative bacillus,
Fusobacterium nucleatum
, in a patient with “culture-negative” meningitis and cerebral abscesses.
Subcutaneous Phaeohyphomycotic Nodule Due to Phialemoniopsis hongkongensis sp. nov
Authors: Tsang Chi-Ching , Chan Jasper F. W. , Ip Philip P. C. , Ngan Antonio H. Y. , Chen Jonathan H. K. , Lau Susanna K. P. , Woo Patrick C. Y. 
Published: June 2014

ABSTRACT

Phialemoniopsis
species are ubiquitous dematiaceous molds associated with a wide variety of superficial and systemic infections in human. In this study, we isolated a mold from the forearm nodule biopsy specimen from a patient with underlying liver cirrhosis, ankylosing spondylosis, and tuberculosis. He was treated with itraconazole, but unfortunately, he succumbed as a result of disseminated tuberculosis with multiorgan failure. The histology results of the skin biopsy showed necrotizing granulomas in which numerous fungal elements were found. On Sabouraud dextrose agar, the fungal isolate grew as white-to-cream and smooth-to-velvety colonies. Microscopically, oval-to-cylindrical conidia were observed from abundant adelophialides, which possessed barely visible parallel collarettes but no basal septa. The azole drugs voriconazole, itraconazole, and posaconazole, as well as amphotericin B, showed high activities against this fungus. Internal transcribed spacer, 28S nuclear ribosomal DNA (nrDNA), and β-actin and β-tubulin gene sequencing showed that this fungus is most closely related to but distinct from
Phialemonium curvata
. Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) and hierarchical cluster analysis showed that the MALDI-TOF MS spectrum of this fungus is most closely related to that of
Phialemonium pluriloculosa
. We propose a new species,
Phialemoniopsis hongkongensis
sp. nov., to describe this fungus.
The Linker Region of NS3 Plays a Critical Role in the Replication and Infectivity of Hepatitis C Virus
Authors: Kohlway Andrew , Pirakitikulr Nathan , Ding Steve C. , Yang Feng , Luo Dahai , Lindenbach Brett D. , Pyle Anna M. 
Published: June 2014

ABSTRACT

Hepatitis C virus (HCV) NS3-4A is required for viral replication and assembly. We establish that virus assembly is sensitive to mutations in the linker region between the helicase and protease domains of NS3-4A. However, we find that the protease cleavage, RNA binding, and unwinding rates of NS3 are minimally affected
in vitro
. Thus, we conclude that the NS3 linker is critical for mediating protein-protein interactions and dynamic control rather than for modulating the enzymatic functions of NS3-4A.