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811.
Atle van Beelen Granlund Arnar Flatberg Ann E. ?stvik Ignat Drozdov Bj?rn I. Gustafsson Mark Kidd Vidar Beisvag Sverre H. Torp Helge L. Waldum Tom Christian Martinsen Jan Kristian Dam?s Terje Espevik Arne K. Sandvik 《PloS one》2013,8(2)
Background
In inflammatory bowel disease (IBD), genetic susceptibility together with environmental factors disturbs gut homeostasis producing chronic inflammation. The two main IBD subtypes are Ulcerative colitis (UC) and Crohn’s disease (CD). We present the to-date largest microarray gene expression study on IBD encompassing both inflamed and un-inflamed colonic tissue. A meta-analysis including all available, comparable data was used to explore important aspects of IBD inflammation, thereby validating consistent gene expression patterns.Methods
Colon pinch biopsies from IBD patients were analysed using Illumina whole genome gene expression technology. Differential expression (DE) was identified using LIMMA linear model in the R statistical computing environment. Results were enriched for gene ontology (GO) categories. Sets of genes encoding antimicrobial proteins (AMP) and proteins involved in T helper (Th) cell differentiation were used in the interpretation of the results. All available data sets were analysed using the same methods, and results were compared on a global and focused level as t-scores.Results
Gene expression in inflamed mucosa from UC and CD are remarkably similar. The meta-analysis confirmed this. The patterns of AMP and Th cell-related gene expression were also very similar, except for IL23A which was consistently higher expressed in UC than in CD. Un-inflamed tissue from patients demonstrated minimal differences from healthy controls.Conclusions
There is no difference in the Th subgroup involvement between UC and CD. Th1/Th17 related expression, with little Th2 differentiation, dominated both diseases. The different IL23A expression between UC and CD suggests an IBD subtype specific role. AMPs, previously little studied, are strongly overexpressed in IBD. The presented meta-analysis provides a sound background for further research on IBD pathobiology. 相似文献812.
Junko Shibayama Tyson G. Taylor Paul W. Venable Nathaniel L. Rhodes Ryan B. Gil Mark Warren Adam R. Wende E. Dale Abel James Cox Kenneth W. Spitzer Alexey V. Zaitsev 《PloS one》2013,8(3)
Rationale
Deterioration of ventricular fibrillation (VF) into asystole or severe bradycardia (electrical failure) heralds a fatal outcome of cardiac arrest. The role of metabolism in the timing of electrical failure remains unknown.Objective
To determine metabolic factors of early electrical failure in an Ex-vivo canine model of cardiac arrest (VF+global ischemia).Methods and Results
Metabolomic screening was performed in left ventricular biopsies collected before and after 0.3, 2, 5, 10 and 20 min of VF and global ischemia. Electrical activity was monitored via plunge needle electrodes and pseudo-ECG. Four out of nine hearts exhibited electrical failure at 10.1±0.9 min (early-asys), while 5/9 hearts maintained VF for at least 19.7 min (late-asys). As compared to late-asys, early-asys hearts had more ADP, less phosphocreatine, and higher levels of lactate at some time points during VF/ischemia (all comparisons p<0.05). Pre-ischemic samples from late-asys hearts contained ∼25 times more inorganic pyrophosphate (PPi) than early-asys hearts. A mechanistic role of PPi in cardioprotection was then tested by monitoring mitochondrial membrane potential (ΔΨ) during 20 min of simulated-demand ischemia using potentiometric probe TMRM in rabbit adult ventricular myocytes incubated with PPi versus control group. Untreated myocytes experienced significant loss of ΔΨ while in the PPi-treated myocytes ΔΨ was relatively maintained throughout 20 min of simulated-demand ischemia as compared to control (p<0.05).Conclusions
High tissue level of PPi may prevent ΔΨm loss and electrical failure at the early phase of ischemic stress. The link between the two protective effects may involve decreased rates of mitochondrial ATP hydrolysis and lactate accumulation. 相似文献813.
Hans-Henrik M. Dahl Teresa Y. C. Ching Wendy Hutchison Sanna Hou Mark Seeto Jessica Sjahalam-King 《PloS one》2013,8(3)
Hearing loss is an etiologically heterogeneous trait with differences in the age of onset, severity and site of lesion. It is caused by a combination of genetic and/or environmental factors. A longitudinal study to examine the efficacy of early intervention for improving child outcomes is ongoing in Australia. To determine the cause of hearing loss in these children we undertook molecular testing of perinatal “Guthrie” blood spots of children whose hearing loss was either detected via newborn hearing screening or detected later in infancy. We analyzed the GJB2 and SLC26A4 genes for the presence of mutations, screened for the mitochondrial DNA (mtDNA) A1555G mutation, and screened for congenital CMV infection in DNA isolated from dried newborn blood spots. Results were obtained from 364 children. We established etiology for 60% of children. One or two known GJB2 mutations were present in 82 children. Twenty-four children had one or two known SLC26A4 mutations. GJB2 or SLC26A4 changes with unknown consequences on hearing were found in 32 children. The A1555G mutation was found in one child, and CMV infection was detected in 28 children. Auditory neuropathy spectrum disorder was confirmed in 26 children whose DNA evaluations were negative. A secondary objective was to investigate the relationship between etiology and audiological outcomes over the first 3 years of life. Regression analysis was used to investigate the relationship between hearing levels and etiology. Data analysis does not support the existence of differential effects of etiology on degree of hearing loss or on progressiveness of hearing loss. 相似文献
814.
Richard M. Oxborough Jovin Kitau Johnson Matowo Emmanuel Feston Rajab Mndeme Franklin W. Mosha Mark W. Rowland 《PloS one》2013,8(2)
Pyrethroid resistant Anopheles gambiae malaria vectors are widespread throughout sub-Saharan Africa and continued efficacy of pyrethroid ITNs is under threat. Chlorfenapyr is a promising pyrrole insecticide with a unique mechanism of action conferring no cross-resistance to existing public health insecticides. Mixtures of chlorfenapyr (CFP) and alphacypermethrin (alpha) may provide additional benefits over chlorfenapyr or alphacypermethrin used alone. An ITN mixture of CFP 100 mg/m2+alpha 25 mg/m2 was compared with CFP 100 mg/m2 and alpha 25 mg/m2 in a small-scale experimental hut trial in an area of wild An. arabiensis. The same treatments were evaluated in tunnel tests against insectary-reared pyrethroid susceptible and resistant Culex quinquefasciatus. Performance was measured in terms of insecticide-induced mortality, and blood-feeding inhibition. Tunnel tests showed that mixtures of CFP 100+ alpha 25 were 1.2 and 1.5 times more effective at killing susceptible Cx. quinquefasciatus than either Alpha 25 (P = 0.001) or CFP 100 (P = 0.001) ITNs. Mixtures of CFP100+ alpha 25 were 2.2 and 1.2 times more effective against resistant Cx. quinquefasciatus than either alpha 25 (P = 0.001) or CFP100 (P = 0.003) ITNs. CFP 100+ alpha 25 produced higher levels of blood-feeding inhibition than CFP alone for susceptible (94 vs 46%, P = 0.001) and resistant (84 vs 53%, P = 0.001) strains. In experimental huts the mixture of CFP 100+ Alpha 25 killed 58% of An. arabiensis, compared with 50% for alpha and 49% for CFP, though the differences were not significant. Blood-feeding inhibition was highest in the mixture with a 76% reduction compared to the untreated net (P = 0.001). ITN mixtures of chlorfenapyr and alphacypermethrin should restore effective control of resistant populations of An. gambiae malaria vectors, provide protection from blood-feeding, and may have benefits for resistance management, particularly in areas with low or moderate frequency of pyrethroid resistance. A wash-resistant mixture should be developed urgently. 相似文献
815.
Linda Penn Martin White Jaana Lindstr?m Annemieke Th. den Boer Ellen Blaak Johan G. Eriksson Edith Feskens Pirjo Ilanne-Parikka Sirkka M. Kein?nen-Kiukaanniemi Mark Walker John C. Mathers Matti Uusitupa Jaakko Tuomilehto 《PloS one》2013,8(2)
Background
Prevalence of type 2 diabetes (T2D) is increasing worldwide. T2D prevention by lifestyle intervention is effective. Pragmatic scalable interventions are needed, with evidence to efficiently target and monitor such interventions. We report pooled analyses of data from three European trial cohorts: to analyse T2D incidence, sustained weight loss and utility of risk predictors.Methods
We analysed data on 749 adults with impaired glucose tolerance (278 men and 471 women, mean age 56 years, mean BMI 31 kgm−2) recruited between 1993 and 2003, and randomised to intensive lifestyle intervention (I) or lifestyle advice control (C). The intervention aimed to increase physical activity, modify diet, and promote weight loss≥5%. Using Cox-regression survival analysis, we assessed T2D incidence and the impact on T2D incidence of sustained weight loss, and of baseline cut-point values of FINDRISC score, fasting plasma glucose (FPG), and HbA1c.Results
Mean follow-up duration was 3.1 years. T2D was diagnosed in 139 participants (I = 45/379, C = 94/370). Cumulative T2D incidence was 57% lower in the intervention compared with the control group (HR 0.42 (95% CI 0.29 to 0.60) P<0.001). Participants with ≥5% weight loss at one year had 65% lower T2D incidence (HR 0.35 (95% CI 0.22 to 0.56) P<0.001); maintaining ≥5% weight loss for two and three years further reduced T2D incidence. Recommended cut-points to identify those at high risk for T2D would have identified different proportions of European Diabetes Prevention Study (EDIPS) participants with similar hazard-ratios for intervention effect.Conclusions
Pooled analysis of EDIPS trial data reinforces evidence for T2D prevention by lifestyle intervention. Analysis showed the preventive effect of ≥5% weight loss, especially if maintained long term, which has utility for intervention monitoring. Analysis of proposed cut-points demonstrates difficulties in balancing risk and benefit, to efficiently target interventions and suggests evidence is needed to define clinical policy.Trial registrations
The Finnish Diabetes Prevention study, Helsinki, Finland: ClinicalTrials.gov; The SLIM diabetes prevention study, Maastricht, The Netherlands: Clinical Trials.gov; NCT00518167 The EDIPS-Newcastle diabetes prevention study, Newcastle upon Tyne, UK: International Standard Randomised Controlled Trial Number; NCT00381186ISRCTN15670600. 相似文献816.
817.
Jeffrey W. Turner Rohinee N. Paranjpye Eric D. Landis Stanley V. Biryukov Narjol González-Escalona William B. Nilsson Mark S. Strom 《PloS one》2013,8(2)
Vibrio parahaemolyticus is a common marine bacterium and a leading cause of seafood-borne bacterial gastroenteritis worldwide. Although this bacterium has been the subject of much research, the population structure of cold-water populations remains largely undescribed. We present a broad phylogenetic analysis of clinical and environmental V. parahaemolyticus originating largely from the Pacific Northwest coast of the United States. Repetitive extragenic palindromic PCR (REP-PCR) separated 167 isolates into 39 groups and subsequent multilocus sequence typing (MLST) separated a subset of 77 isolates into 24 sequence types. The Pacific Northwest population exhibited a semi-clonal structure attributed to an environmental clade (ST3, N = 17 isolates) clonally related to the pandemic O3:K6 complex and a clinical clade (ST36, N = 20 isolates) genetically related to a regionally endemic O4:K12 complex. Further, the identification of at least five additional clinical sequence types (i.e., ST43, 50, 65, 135 and 417) demonstrates that V. parahaemolyticus gastroenteritis in the Pacific Northwest is polyphyletic in nature. Recombination was evident as a significant source of genetic diversity and in particular, the recA and dtdS alleles showed strong support for frequent recombination. Although pandemic-related illnesses were not documented during the study, the environmental occurrence of the pandemic clone may present a significant threat to human health and warrants continued monitoring. It is evident that V. parahaemolyticus population structure in the Pacific Northwest is semi-clonal and it would appear that multiple sequence types are contributing to the burden of disease in this region. 相似文献
818.
Halvor Rollag Thor Ueland Anders ?sberg Anders Hartmann Alan G. Jardine Atul Humar Mark D. Pescovitz Angelo A. Bignamini P?l Aukrust 《PloS one》2013,8(4)
Background
While several studies have examined the general inflammatory responses in relation to cytomegalovirus infection, the identification of the various inflammatory mediators as well as their relative importance is far from clear.Patients and Methods
Solid organ recipients enrolled in an international multicenter trial of cytomegalovirus disease treatment (the VICTOR study) were analyzed (n = 289) (ClinicalTrials.gov ). Plasma markers of inflammation and endothelial cell activation were assessed at baseline by enzyme immunoassays. NCT00431353Results
The major findings were: (i) Plasma levels of the CXC-chemokine interferon-inducible protein-10 (P<0.001) and C-reactive protein (P = 0.046) were independently associated with the presence of cytomegalovirus DNAemia above lower level of quantification. (ii) High levels of CC-chemokine ligand 21 (P = 0.027) and pentraxin 3 (P = 0.033) were independently associated with tissue invasive cytomegalovirus disease as opposed to cytomegalovirus syndrome.Conclusion
Our findings illustrate the complex interaction between cytomegalovirus and the immune system, involving a wide range of inflammatory mediators that could be associated to disease manifestations in cytomegalovirus related disease. 相似文献819.
Thomas B. Nicholson Anup K. Singh Hui Su Sarah Hevi Jing Wang Jeff Bajko Mei Li Reginald Valdez Margaret Goetschkes Paola Capodieci Joseph Loureiro Xiaodong Cheng En Li Bernd Kinzel Mark Labow Taiping Chen 《PloS one》2013,8(4)
Lysine-specific demethylase 1 (Lsd1/Aof2/Kdm1a), the first enzyme with specific lysine demethylase activity to be described, demethylates histone and non-histone proteins and is essential for mouse embryogenesis. Lsd1 interacts with numerous proteins through several different domains, most notably the tower domain, an extended helical structure that protrudes from the core of the protein. While there is evidence that Lsd1-interacting proteins regulate the activity and specificity of Lsd1, the significance and roles of such interactions in developmental processes remain largely unknown. Here we describe a hypomorphic Lsd1 allele that contains two point mutations in the tower domain, resulting in a protein with reduced interaction with known binding partners and decreased enzymatic activity. Mice homozygous for this allele die perinatally due to heart defects, with the majority of animals suffering from ventricular septal defects. Molecular analyses revealed hyperphosphorylation of E-cadherin in the hearts of mutant animals. These results identify a previously unknown role for Lsd1 in heart development, perhaps partly through the control of E-cadherin phosphorylation. 相似文献
820.
Judith Brouwers Rintis Noviyanti Rob Fijnheer Philip G. de Groot Leily Trianty Siti Mudaliana Mark Roest Din Syafruddin Andre van der Ven Quirijn de Mast 《PloS one》2013,8(6)