bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combatting bacterial infections by killing persister cells with mitomycin C
Authors: Kwan Brian W. , Chowdhury Nityananda , Wood Thomas K. 
Published: April 2015

SummaryPersister cells are a multi‐drug tolerant subpopulation of bacteria that contribute to chronic and recalcitrant clinical infections such as cystic fibrosis and tuberculosis. Persisters are metabolically dormant, so they are highly tolerant to all traditional antibiotics which are mainly effective against actively growing cells. Here, we show that the FDA‐approved anti‐cancer drug mitomycin C (MMC) eradicates persister cells through a growth‐independent mechanism. MMC is passively transported and bioreductively activated, leading to spontaneous cross‐linking of DNA, which we verify in both active and dormant cells. We find MMC effectively eradicates cells grown in numerous different growth states (e.g. planktonic cultures and highly robust biofilm cultures) in both rich and minimal media. Additionally, MMC is a potent bactericide for a broad range of bacterial persisters, including commensal Escherichia coli K‐12 as well as pathogenic species of E. coli, Staphylococcus aureus and Pseudomonas aeruginosa. We also demonstrate the efficacy of MMC in an animal model and a wound model, substantiating the clinical applicability of MMC against bacterial infections. Therefore, MMC is the first broad‐spectrum compound capable of eliminating persister cells, meriting investigation as a new approach for the treatment of recalcitrant infections.
Rare taxa have potential to make metabolic contributions in enhanced biological phosphorus removal ecosystems
Authors: Lawson Christopher E. , Strachan Blake J. , Hanson Niels W. , Hahn Aria S. , Hall Eric R. , Rabinowitz Barry , Mavinic Donald S. , Ramey William D. , Hallam Steven J. 
Published: April 2015

SummaryEnhanced biological phosphorus removal (EBPR) relies on diverse but specialized microbial communities to mediate the cycling and ultimate removal of phosphorus from municipal wastewaters. However, little is known about microbial activity and dynamics in relation to process fluctuations in EBPR ecosystems. Here, we monitored temporal changes in microbial community structure and potential activity across each bioreactor zone in a pilot‐scale EBPR treatment plant by examining the ratio of small subunit ribosomal RNA (SSU rRNA) to SSU rRNA gene (rDNA) over a 120 day study period. Although the majority of operational taxonomic units (OTUs) in the EBPR ecosystem were rare, many maintained high potential activities based on SSU rRNA : rDNA ratios, suggesting that rare OTUs contribute substantially to protein synthesis potential in EBPR ecosystems. Few significant differences in OTU abundance and activity were observed between bioreactor redox zones, although differences in temporal activity were observed among phylogenetically cohesive OTUs. Moreover, observed temporal activity patterns could not be explained by measured process parameters, suggesting that other ecological drivers, such as grazing or viral lysis, modulated community interactions. Taken together, these results point towards complex interactions selected for within the EBPR ecosystem and highlight a previously unrecognized functional potential among low abundance microorganisms in engineered ecosystems.
Binge Drinking During Adolescence Disrupts Se Homeostasis and Its Main Hepatic Selenoprotein Expression
Authors: Ojeda María Luisa , Rua Rui Manuel , Murillo María Luisa , Carreras Olimpia , Nogales Fátima 
Published: April 2015

BackgroundBinge drinking (BD) is the most common ethanol (EtOH) intake consumption model among teenagers, but little is known about its effects on the liver. During its hepatic metabolism, acute alcohol exposure produces a great amount of reactive oxygen species which contributes to alcohol‐induced liver injury. Selenium (Se) plays a key role in antioxidant defense as it forms part of selenoproteins, such as the antioxidant glutathione peroxidases (GPxs) or the selenoprotein P (SelP), synthesized mainly in liver. Chronic EtOH consumption decreases both Se deposits and this tissue's antioxidant activity.MethodsTwo BD administration routes (oral and intraperitoneal) were used in adolescent rats to analyze Se homeostasis; the main hepatic selenoproteins’ expression: GPx1, GPx4, and SelP, and their biological roles related to oxidation. Their relationship with inflammatory processes was also determined by analyzing the expression of the transcriptional factor nuclear factor‐kappa beta (NF‐κB).ResultsIt has been demonstrated for the first time that BD in adolescents alters Se homeostasis regardless of the administration route employed, despite the fact that the BD oral group ingested less Se in diet. This decrease of Se in serum and liver is directly related to a decrease in serum GPx3 and hepatic GPx1 activity, contributing to the oxidative imbalance found. The depletion of Se detected in liver affects GPx1 expression and, surprisingly, GPx4 expression. This could be related to the lower expression of the transcriptional factor NF‐κB in the liver, a key player in the regulation of inflammatory processes.ConclusionsDue to the above, and to find whether a Se supplementation therapy improves these situations, it would be interesting to explore in more depth the relationship between Se, the high oxidation found, and the depressed immune response reported in BD adolescents.
Polygenic risk for alcohol dependence associates with alcohol consumption, cognitive function and social deprivation in a population‐based cohort
Authors: Clarke Toni‐Kim , Smith Andrew H. , Gelernter Joel , Kranzler Henry R. , Farrer Lindsay A. , Hall Lynsey S. , Fernandez‐Pujals Ana M. , MacIntyre Donald J. , Smith Blair H. , Hocking Lynne J. , Padmanabhan Sandosh , Hayward Caroline , Thomson Pippa A. , Porteous David J. , Deary Ian J. , McIntosh Andrew M. 
Published: April 2015

AbstractAlcohol dependence is frequently co‐morbid with cognitive impairment. The relationship between these traits is complex as cognitive dysfunction may arise as a consequence of heavy drinking or exist prior to the onset of dependence. In the present study, we tested the genetic overlap between cognitive abilities and alcohol dependence using polygenic risk scores (PGRS). We created two independent PGRS derived from two recent genome‐wide association studies (GWAS) of alcohol dependence (SAGE GWAS: n = 2750; Yale‐Penn GWAS: n = 2377) in a population‐based cohort, Generation Scotland: Scottish Family Health Study (GS:SFHS) (n = 9863). Data on alcohol consumption and four tests of cognitive function [Mill Hill Vocabulary (MHV), digit symbol coding, phonemic verbal fluency (VF) and logical memory] were available. PGRS for alcohol dependence were negatively associated with two measures of cognitive function: MHV (SAGE: P = 0.009, β = −0.027; Yale‐Penn: P = 0.001, β = −0.034) and VF (SAGE: P = 0.0008, β = −0.036; Yale‐Penn: P = 0.00005, β = −0.044). VF remained robustly associated after adjustment for education and social deprivation; however, the association with MHV was substantially attenuated. Shared genetic variants may account for some of the phenotypic association between cognitive ability and alcohol dependence. A significant negative association between PGRS and social deprivation was found (SAGE: P = 5.2 × 10−7, β = −0.054; Yale‐Penn: P = 0.000012, β = −0.047). Individuals living in socially deprived regions were found to carry more alcohol dependence risk alleles which may contribute to the increased prevalence of problem drinking in regions of deprivation. Future work to identify genes which affect both cognitive impairment and alcohol dependence will help elucidate biological processes common to both disorders.
Lack of genetic association of 5‐HTR2A 102 T/C and ‐1438A/G polymorphisms with Tourette syndrome in a family‐based association study in a Chinese Han population
Authors: Xu Longqiang , Zheng Lanlan , Ma Jianhua , Su Nailun , Liu Yujun , Ma Xu , Zhang Xinhua , Liu Shiguo 
Published: April 2015

AbstractIntroductionOur purpose is to investigate whether polymorphisms of 102 T/C and ‐1438A/G in 5HTR2A are associated with Tourette syndrome (TS) in Chinese Han population.MethodsA total of 178 TS trios were recruited in this study. After the allelic and genotypic distributions of two polymorphisms were genotyped using polymerase chain reaction and restriction fragment length polymorphism (PCR‐RFLP), we compared their genetic distributions with what is expected with Hardy–Weinberg to explore whether there might be an association of these polymorphisms with TS by haplotype relative risk (HRR) and transmission disequilibrium test (TDT) statistics.ResultsOur results showed that no significant associations were found between the HTR2A 102 T/C and ‐1438A/G polymorphisms and TS (for HTR2A 102 T/C: TDT = 2.041, df = 1, P = 0.175; HRR = 1.468, χ2 = 1.905, P = 0.168, 95% confidence interval: 0.850–2.535; for HTR2A: ‐1438A/G, TDT = 0.093, df = 1, P = 0.819; HRR = 0.965, χ2 = 0.018, P = 0.894, 95% confidence interval: 0.574–1.624).DiscussionOur study suggested that the HTR2A 102T/C and ‐1438A/G polymorphisms may not be associated with susceptibility to TS, and thus do not play a major role in the development of TS in the Chinese Han population. However, these results need to be confirmed in a larger sample collected from different populations.
Shades of green andREDD: Local and global contestations over the value of forest versus plantation development on the Indonesian forest frontier
Authors: Eilenberg Michael 
Published: April 2015

AbstractIn a time of increasing land enclosures sparked by large‐scale environmental initiatives and agricultural expansion, this paper examines local and global contestations over the value of forest on an Indonesian forest frontier. Engaging with recent debates on carbon forestry, the paper problematises the emerging initiatives of ‘ReducingEmissions fromDeforestation and ForestDegradation’ known asREDD+ in the province ofWestKalimantan,Indonesia. The paper argues that the general rush to implementREDD+ without intimate knowledge of the political landscape of resource struggle is in danger of generating new enclosures of land that may be easily appropriated by local elites, thus excluding less fortunate sections of local society. The paper shows how divergent interpretations ofREDD+ are triggering land disputes, and how powerful actors readily appropriateREDD+ discourses as a tool to support divergent claims of land ownership. Government and villagers, through overlapping and contradictory engagements, negotiateREDD+ initiatives with global environmental actors and private plantation companies. The paper highlights the implications of these local realities for the successes ofREDD+. TheKalimantan case highlights some of the dilemmas of carbon mitigation initiatives experienced in frontier regions throughoutSoutheastAsia, places that have become prime battlefronts of large‐scale climate change initiatives and agrarian expansion.
The portable sawmill and other challenges toREDD+ inPapuaNewGuinea
Authors: Dalsgaard Steffen , Pedersen Marianne 
Published: April 2015

AbstractThe future forReducingEmissions fromDeforestation andForestDegradationPlus (REDD+) inPapuaNewGuinea (PNG) is uncertain. Logging companies have been accessing land via a controversial legal framework calledSpecialAgriculturalBusinessLease, while conservation non‐government organisations are struggling to find schemes to stop the deforestation.REDD+ has been the new favoured approach. However, there are as yet only a few pilot projects, several of which are in areas without large‐scale logging. WhetherREDD+ has a future inPNGis difficult to know. It may come to share the fate of the portable sawmill – a technology previously assumed to promote sustainable community logging, but is now adopted by the commercial logging industry and providing new challenges to conversation efforts. This article argues that to understand the possibility for successfully implementingREDD+, it is necessary to look at the development of the forestry sector in the widest possible terms. This involves analysing the different competing actors, technologies and forms of social organisation that are employed to gain control of species deemed valuable to either conservation or commercial resource exploitation.
l‐Arginine Attenuates Cardiac Dysfunction, But Further Down‐Regulates α‐Myosin Heavy Chain Expression in Isoproterenol‐Induced Cardiomyopathy
Authors: Kralova Eva , Doka Gabriel , Pivackova Lenka , Srankova Jasna , Kuracinova Kristina , Janega Pavol , Babal Pavel , Klimas Jan , Krenek Peter 
Published: April 2015

AbstractIn view of previously reported increased capacity for nitric oxide production, we suggested that l‐arginine (ARG), the nitric oxide synthase (NOS) substrate, supplementation would improve cardiac function in isoproterenol (ISO)‐induced heart failure. Male Wistar rats were treated with ISO for 8 days (5 mg/kg/day, i.p.) or vehicle. ARG was given to control (ARG) and ISO‐treated (ISO+ARG) rats in water (0.4 g/kg/day). ISO administration was associated with 40% mortality, ventricular hypertrophy, decreased heart rate, left ventricular dysfunction, fibrosis and ECG signs of ischaemia. RT‐PCR showed increased mRNA levels of cardiac hypertrophy marker atrial natriuretic peptide, but not BNP, decreased expression of myosin heavy chain isoform MYH6 and unaltered expression of pathological MYH7. ISO increased the protein levels of endothelial nitric oxide synthase, but at the same time it markedly up‐regulated mRNA and protein levels of gp91phox, a catalytical subunit of superoxide‐producing NADPH oxidase. Fibrosis was markedly increased by ISO. ARG treatment moderately ameliorated left ventricular dysfunction, but was without effect on cardiac hypertrophy and fibrosis. Combination of ISO and ARG led to a decrease in cav‐1 expression, a further increase in MYH7 expression and a down‐regulation of MYH6 that inversely correlated with gp91phox mRNA levels. Although ARG, at least partially, improved ISO‐impaired basal left ventricular systolic function, it failed to reduce cardiac hypertrophy, fibrosis, oxidative stress and mortality. The protection of contractile performance might be related to increased capacity for nitric oxide production and the up‐regulation of MYH7 which may compensate for the marked down‐regulation of the major MYH6 isoform.
Doubly‐robust dynamic treatment regimen estimation via weighted least squares
Authors: Wallace Michael P. , Moodie Erica E. M. 
Published: April 2015

SummaryPersonalized medicine is a rapidly expanding area of health research wherein patient level information is used to inform their treatment. Dynamic treatment regimens (DTRs) are a means of formalizing the sequence of treatment decisions that characterize personalized management plans. Identifying the DTR which optimizes expected patient outcome is of obvious interest and numerous methods have been proposed for this purpose. We present a new approach which builds on two established methods: Q‐learning and G‐estimation, offering the doubly robust property of the latter but with ease of implementation much more akin to the former. We outline the underlying theory, provide simulation studies that demonstrate the double‐robustness and efficiency properties of our approach, and illustrate its use on data from the Promotion of Breastfeeding Intervention Trial.
Set‐based tests for genetic association in longitudinal studies
Authors: He Zihuai , Zhang Min , Lee Seunggeun , Smith Jennifer A. , Guo Xiuqing , Palmas Walter , Kardia Sharon L. R. , Roux Ana V. Diez , Mukherjee Bhramar 
Published: April 2015

SummaryGenetic association studies with longitudinal markers of chronic diseases (e.g., blood pressure, body mass index) provide a valuable opportunity to explore how genetic variants affect traits over time by utilizing the full trajectory of longitudinal outcomes. Since these traits are likely influenced by the joint effect of multiple variants in a gene, a joint analysis of these variants considering linkage disequilibrium (LD) may help to explain additional phenotypic variation. In this article, we propose a longitudinal genetic random field model (LGRF), to test the association between a phenotype measured repeatedly during the course of an observational study and a set of genetic variants. Generalized score type tests are developed, which we show are robust to misspecification of within‐subject correlation, a feature that is desirable for longitudinal analysis. In addition, a joint test incorporating gene–time interaction is further proposed. Computational advancement is made for scalable implementation of the proposed methods in large‐scale genome‐wide association studies (GWAS). The proposed methods are evaluated through extensive simulation studies and illustrated using data from the Multi‐Ethnic Study of Atherosclerosis (MESA). Our simulation results indicate substantial gain in power using LGRF when compared with two commonly used existing alternatives: (i) single marker tests using longitudinal outcome and (ii) existing gene‐based tests using the average value of repeated measurements as the outcome.
Acute myeloid leukaemia: challenges and real world data from India
Authors: Philip Chepsy , George Biju , Ganapule Abhijeet , Korula Anu , Jain Punit , Alex Ansu Abu , Lakshmi Kavitha M. , Sitaram Usha , Abubacker Fouzia N. , Abraham Aby , Viswabandya Auro , Srivastava Vivi M. , Srivastava Alok , Balasubramanian Poonkuzhali , Mathews Vikram 
Published: April 2015

SummaryThe management of acute myeloid leukaemia (AML) in India remains a challenge. In a two‐year prospective study at our centre there were 380 newly diagnosed AML (excluding acute promyelocytic leukaemia, AML‐M3) patients. The median age of newly diagnosed patients was 40 years (range: 1–79; 12·3% were ≤ 15 years, 16·3% were ≥ 60 years old) and there were 244 (64·2%) males. The median duration of symptoms prior to first presentation at our hospital was 4 weeks (range: 1–52). The median distance from home to hospital was 580 km (range: 6–3200 km). 109 (29%) opted for standard of care and were admitted for induction chemotherapy. Of the 271 that did not take treatment the major reason was lack of financial resources in 219 (81%). There were 27 (24·7%) inductions deaths and of these, 12 (44·5%) were due to multidrug‐resistant gram‐negative bacilli and 12 (44·5%) showed evidence of a fungal infection. The overall survival at 1 year was 70·4% ± 10·7%, 55·6% ± 6·8% and 42·4% ± 15·6% in patients aged ≤15 years, 15 ‐ 60 years and ≥60 years, respectively. In conclusion, the biggest constraint is the cost of treatment and the absence of a health security net to treat all patients with this diagnosis.
The genes Scgb1a1, Lpo and Gbp2 characteristically expressed in peri‐implant epithelium of rats
Authors: Mori Gentaro , Sasaki Hodaka , Makabe Yasushi , Yoshinari Masao , Yajima Yasutomo 
Published: April 2015

AbstractObjectivesThe peri‐implant epithelium (PIE) plays an important role in the prevention against initial stage of inflammation. To minimize the risk of peri‐implantitis, it is necessary to understand the biological characteristics of the PIE. The aim of this study was to investigate the characteristic gene expression profile of PIE as compared to junctional epithelium (JE) using laser microdissection and microarray analysis.MethodsLeft upper first molars of 4‐week‐old rat were extracted, and titanium alloy implants were placed. Four weeks after surgery, samples were harvested by laser microdissection, and total RNA samples were isolated. Comprehensive analyses of genes expressed in the JE and PIE were performed using microarray analysis. Confirmation of the differential expression of selected genes was performed by quantitative real‐time polymerase chain reaction and immunohistochemistry.ResultsThe microarray analysis showed that 712 genes were more than twofold change upregulated in the PIE compared with the JE. Genes Scgb1a1 were significantly upregulated more than 19.1‐fold, Lpo more than 19.0‐fold, and Gbp2 more than 8.9‐fold, in the PIE (P < 0.01). Immunohistochemical localization of SCGB1A1, LPO, and GBP2 was observed in PIE.ConclusionThe present results suggested that genes Scgb1a1, Lpo, and Gbp2 are characteristically expressed in the PIE.
Tests of Eustachian tube function: a review
Authors: Smith M.E. , Tysome J.R. 
Published: April 2015

BackgroundEustachian tube (ET) dysfunction is a common but poorly understood cause of patient symptoms, and an important aetiological factor in the development of middle ear pathology. Despite this, there are no specific tests of ET function in widespread clinical use and no identified ‘gold standard’ with which to diagnose the disease.ObjectiveThis review aims to review the literature to identify currently available tests of ET function and, where possible, report on their accuracy.Type of reviewNarrative systematic review.Search strategyMEDLINE, EMBASE, Biosis and the Cochrane library were searched and reference lists reviewed for relevant articles.Evaluation methodTests in included studies were required to measure a physiological function of the ET, or play a role in the diagnosis of poor ET function. Significant variation in demographic characteristics, disease presentation and severity, and technological approaches only permitted narrative systematic review.ResultsWhile many tests of ET function have been developed, with some in routine clinical use, all have significant limitations. Published accuracy data are limited and of differing quality due to the variability incomparative tests, and the spectrum of otological disorders associated with ET dysfunction.ConclusionsCurrently, no single test could be considered a ‘gold standard’ for the diagnosis of ET dysfunction, but there is some evidence that diagnostic accuracy can be improved by combining the results of different objective tests and patient‐reported outcome measures. Further development of ET function tests is required to facilitate the accurate diagnosis of patients and allow outcome reporting for new interventions.
Use of HSI to measure oxygen saturation in the lower limb and its correlation with healing of foot ulcers in diabetes
Authors: Jeffcoate W. J. , Clark D. J. , Savic N. , Rodmell P. I. , Hinchliffe R. J. , Musgrove A. , Game F. L. 
Published: April 2015

AbstractAimTo explore the use of hyperspectral imaging (HSI) to predict healing of diabetic foot ulcers in patients with diabetes.MethodsWe used a HSI technique that incorporated novel software to account for tissue scattering of light, and was validated using blood samples of varying oxygen saturation assessed by blood gas analysis. HSI was then performed on a population newly presenting with diabetic foot ulcers to a specialist clinic, and associations were sought with healing at 12 and 24 weeks.ResultsThe correlation between the results of HSI and blood gas analysis was strong (r = 0.994). A total of 43 patients (mean ± sd age 62.7 ± 12.2 years; 31 men, 12 women; 37 with Type 2 diabetes, six with Type 1 diabetes) with foot ulcers were included in the prospective clinical study and underwent HSI within 16 days of presentation. In all, 26 ulcers healed within 12 weeks and 28 within 24 weeks. There was a negative association between tissue oxygenation assessed by HSI at baseline and healing by 12 weeks (P = 0.009), and this was observed in both infected and non‐infected ulcers. There was a significant positive correlation between oxygenation assessed by HSI and time to healing (P = 0.03). No correlations were observed at 24 weeks.ConclusionsThese findings suggest that HSI may predict healing in routine practice. The fact that the correlation between HSI and healing was negative could be explained by HSI being a measure of oxygenation of haemoglobin and there may be an inverse relationship between this and the oxygenation of extravascular tissue in people with neuropathy and/or microvascular disease.