bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterologous Expression of Lysergic Acid and Novel Ergot Alkaloids in Aspergillus fumigatus
Authors: Robinson Sarah L. , Panaccione Daniel G. 
Published: August 2014

ABSTRACT

Different lineages of fungi produce distinct classes of ergot alkaloids. Lysergic acid-derived ergot alkaloids produced by fungi in the Clavicipitaceae are particularly important in agriculture and medicine. The pathway to lysergic acid is partly elucidated, but the gene encoding the enzyme that oxidizes the intermediate agroclavine is unknown. We investigated two candidate agroclavine oxidase genes from the fungus
Epichloë festucae
var.
lolii
×
Epichloë typhina
isolate Lp1 (henceforth referred to as
Epichloë
sp. Lp1), which produces lysergic acid-derived ergot alkaloids. Candidate genes
easH
and
cloA
were expressed in a mutant strain of the mold
Aspergillus fumigatus
, which typically produces a subclass of ergot alkaloids not derived from agroclavine or lysergic acid. Candidate genes were coexpressed with the
Epichloë
sp. Lp1 allele of
easA
, which encodes an enzyme that catalyzed the synthesis of agroclavine from an
A. fumigatus
intermediate; the agroclavine then served as the substrate for the candidate agroclavine oxidases. Strains expressing
easA
and
cloA
from
Epichloë
sp. Lp1 produced lysergic acid from agroclavine, a process requiring a cumulative six-electron oxidation and a double-bond isomerization. Strains that accumulated excess agroclavine (as a result of
Epichloë
sp. Lp1
easA
expression in the absence of
cloA
) metabolized it into two novel ergot alkaloids for which provisional structures were proposed on the basis of mass spectra and precursor feeding studies. Our data indicate that CloA catalyzes multiple reactions to produce lysergic acid from agroclavine and that combining genes from different ergot alkaloid pathways provides an effective strategy to engineer important pathway molecules and novel ergot alkaloids.
Bacteriological Effects of Dentifrices with and without Active Ingredients of Natural Origin
Authors: Ledder Ruth G. , Latimer Joe , Humphreys Gavin J. , Sreenivasan Prem K. , McBain Andrew J. 
Published: August 2014

ABSTRACT
Compounds of natural origin are increasingly used as adjuncts to oral hygiene. We have adopted four distinct approaches to assess the antibacterial activity of dentifrices containing natural active ingredients against oral bacteria in several test systems. Corsodyl Daily (CD), Kingfisher Mint (KM), and Parodontax fluoride (PF) were compared to a dentifrice containing fluoride (Colgate Cavity Protection [CCP]) and one containing triclosan (Colgate Total [CT]). The growth inhibitory and bactericidal potency of the formulations were determined for 10 isolated oral bacteria. Effects of single exposures of simulated supragingival plaques were then determined by epifluorescence and confocal microscopy, while the effects of repeated exposures were quantified by viable counting. Additionally, dense plaques, maintained in continuous culture, were repeatedly dosed, and the outcome was assessed by viable counting and eubacterial DNA profiling. The test dentifrices exhibited variable specificity and potency against oral bacteria in axenic culture. Of the herbal formulations, KM caused the largest viability reductions in simulated supragingival plaques, with CT causing the greatest reductions overall. Following single exposures, CD caused moderate reductions, while PF had no effect. After multiple dosing, all formulations significantly reduced numbers of total, facultative, and Gram-negative anaerobes, but only KM and CT caused greater reductions than the fluoride control. KM also reduced counts of streptococci (rank order of effectiveness: CT > KM > CCP > PF > CD). Marked changes in eubacterial DNA profiles were not detected for any herbal formulation in dense plaques, although KM markedly reduced viable counts of streptococci, in agreement with supragingival data. While both nonherbal comparators displayed antibacterial activity, the triclosan-containing formulation caused greater viability reductions than the herbal and nonherbal formulations.
Membrane Dynamics at the Nuclear Exchange Junction during Early Mating (One to Four Hours) in the Ciliate Tetrahymena thermophila
Authors: Cole Eric S. , Giddings Thomas H. , Ozzello Courtney , Winey Mark , O'Toole Eileen , Orias Judy , Hamilton Eileen , Guerrier Sabrice , Ballard Anna , Aronstein Tyler 
Published: August 2014

ABSTRACT

Using serial-section transmission electron microscopy and three-dimensional (3D) electron tomography, we characterized membrane dynamics that accompany the construction of a nuclear exchange junction between mating cells in the ciliate
Tetrahymena thermophila
. Our methods revealed a number of previously unknown features. (i) Membrane fusion is initiated by the extension of hundreds of 50-nm-diameter protrusions from the plasma membrane. These protrusions extend from both mating cells across the intercellular space to fuse with membrane of the mating partner. (ii) During this process, small membrane-bound vesicles or tubules are shed from the plasma membrane and into the extracellular space within the junction. The resultant vesicle-filled pockets within the extracellular space are referred to as junction lumens. (iii) As junction lumens fill with extracellular microvesicles and swell, the plasma membrane limiting these swellings undergoes another deformation, pinching off vesicle-filled vacuoles into the cytoplasm (reclamation). (iv) These structures (resembling multivesicular bodies) seem to associate with autophagosomes abundant near the exchange junction. We propose a model characterizing the membrane-remodeling events that establish cytoplasmic continuity between mating
Tetrahymena
cells. We also discuss the possible role of nonvesicular lipid transport in conditioning the exchange junction lipid environment. Finally, we raise the possibility of an intercellular signaling mechanism involving microvesicle shedding and uptake.
Renal histological heterogeneity and functional progress in normoalbuminuric and microalbuminuric Japanese patients with type 2 diabetes
Authors: Moriya Tatsumi , Suzuki Yoshiki , Inomata Shigeki , Iwano Masayuki , Kanauchi Masao , Haneda Masakazu 
Published: August 2014

Background and objectivesRenal histological injury patterns in type 2 diabetes are heterogeneous. We compared renal histological injury patterns using renal biopsy findings with renal function and followed up renal functional changes in normoalbuminuric and microalbuminuric patients with type 2 diabetes to determine whether renal function progresses according to injury patterns.Design, setting, participants, and measurementsWe examined 111 patients with type 2 diabetes with percutaneous renal biopsy (78 men, 52±11 years old, 59 normoalbuminuria, 52 microalbuminuria) and followed up 37 cases for 11 years. Light microscopy of tissues revealed renal injury patterns as: category I (CI), normal or near-normal structure; category II (CII), typical diabetic glomerulopathy; category III (CIII), atypical (disproportionately severe tubulointerstitial/vascular damage with no/mild glomerulopathy).ResultsThere were 29 CI, 62 CII, and 20 CIII patients. CII patients had a higher frequency of chronic kidney disease (CKD) G3-4, while the injury pattern distribution was not different among the albuminuria stages. The mean glomerular volume and volume fraction of cortical interstitium were larger than those of controls. The arteriolar hyalinosis index was larger in CII and CIII, while the percent global glomerular sclerosis was larger in CKD G3-4 compared with CKD G1-2. Renal function at follow-up was decreased in CII and CIII compared with the baseline estimated glomerular filtration rate (eGFR), while the GFR decline rate was faster in CII.ConclusionsIn normoalbuminuric and microalbuminuric patients with type 2 diabetes, loss of GFR could indicate typical diabetic glomerulosclerosis and a high frequency of global glomerular sclerosis. Urinary biomarkers identifying histological patterns of renal injury are necessary because GFR decline rates differed according to histological injury patterns.
How do adults with physical disability experience primary care? A nationwide cross-sectional survey of access among patients in England
Authors: Popplewell Nicola T A , Rechel Boika P D , Abel Gary A 
Published: August 2014

ObjectivesAlmost a quarter of adults in England report a longstanding condition limiting physical activities. However, recent overseas evidence suggests poorer access to healthcare for disabled people. This study aimed to compare patient-reported access to English primary care for adults with and without physical disability.DesignSecondary analysis of the 2010/11 General Practice Patient Survey (response rate 35.9%) using logistic regression.Setting and participants1 780 977 patients, from 8384 English general practices, who provided information on longstanding conditions limiting basic physical activity. 41 389 of these patients reported unmet need to see a doctor in the previous 6 months.OutcomesDifficulty getting to the general practitioner (GP) surgery as a reason for unmet need to see a doctor in the preceding 6 months; difficulty getting into the surgery building.ResultsEstimated prevalence of physical disability was 17.2% (95% CI 17.0% to 17.3%). 17.9% (95% CI 17.4% to 18.4%) of patients with an unmet need to see a doctor were estimated to experience this due to difficulty getting to the surgery, and 2.2% (95% CI 2.2% to 2.3%) of all patients registered with a GP were estimated to experience difficulty getting into surgery buildings. Adjusting for gender, age, health status and employment, difficulty getting to the surgery explaining unmet need was more likely for patients with physical disability than for those without. Similarly, difficulty getting into surgery buildings was more likely among physically disabled patients. Both associations were stronger among patients aged 65–84 years.ConclusionsAdults in England with physical disability experience worse physical access into primary care buildings than those without. Physical disability is also associated with increased unmet healthcare need due to difficulty getting to GP premises, compared with the experience of adults without physical disability. Increasing age further exacerbates these problems. Access to primary care in England for patients with physical disability needs improving.
Creating political priority for micronutrient deficiencies: a qualitative case study from Senegal
Authors: Balarajan Yarlini 
Published: August 2014

ObjectivesTo examine what factors influence the agenda-setting process and level of political priority afforded to micronutrient deficiencies (MNDs).DesignQualitative case study employing process tracing, informed by primary data collected from semistructured interviews with policymakers.SettingDakar, Senegal.ResultsSeveral facilitating and impeding factors affecting the level of political prioritisation for MNDs were identified. Facilitating factors included multiple stakeholders using aligned framing to collectively advocate for MNDs; availability of indicators to quantify issue severity and raise awareness; and transnational advocacy activities around micronutrients. Impeding factors included lack of awareness among policymakers and civil society about MNDs; issue complexity, with the need for coordinated multisectoral response to deliver a complex package of solutions; lack of resources trapping the issue in a ‘low-priority’ cycle; lack of a policy champion to advocate for the issue and the challenge of demonstrating the effectiveness of interventions to support advocacy efforts.ConclusionsThis study gives insight into the political prioritisation process for MNDs from the perspective of key stakeholders working at the national level in Senegal. In doing so, the study offers some explanation as to why the issue of MNDs has struggled to gain political attention and make it onto the national policy agenda. Moving forward, greater awareness of the factors affecting agenda setting for MNDs may help to devise political strategies to champion this development issue in countries with high burdens of micronutrient deficiencies.
Pair-wise comparison analysis of differential expression of mRNAs in early and advanced stage primary colorectal adenocarcinomas
Authors: Lau Tze Pheng , Roslani April Camilla , Lian Lay Hoong , Chai Hwa Chia , Lee Ping Chin , Hilmi Ida , Goh Khean Lee , Chua Kek Heng 
Published: August 2014

ObjectivesTo characterise the mRNA expression patterns of early and advanced stage colorectal adenocarcinomas of Malaysian patients.DesignComparative expression analysis.Setting and participantsWe performed a combination of annealing control primer (ACP)-based PCR and reverse transcription-quantitative real-time PCR for the identification of differentially expressed genes (DEGs) associated with early and advanced stage primary colorectal tumours. We recruited four paired samples from patients with colorectal cancer (CRC) of Dukes’ A and B for the preliminary differential expression study, and a total of 27 paired samples, ranging from CRC stages I to IV, for subsequent confirmatory test. The tumouric samples were obtained from the patients with CRC undergoing curative surgical resection without preoperative chemoradiotherapy. The recruited patients with CRC were newly diagnosed with CRC, and were not associated with any hereditary syndromes, previously diagnosed cancer or positive family history of CRC. The paired non-cancerous tissue specimens were excised from macroscopically normal colonic mucosa distally located from the colorectal tumours.Primary and secondary outcome measuresThe differential mRNA expression patterns of early and advanced stage colorectal adenocarcinomas compared with macroscopically normal colonic mucosa were characterised by ACP-based PCR and reverse transcription-quantitative real-time PCR.ResultsTheRPL35,RPS23andTIMP1genes were found to be overexpressed in both early and advanced stage colorectal adenocarcinomas (p<0.05). However, theARPC2gene was significantly underexpressed in early colorectal adenocarcinomas, while the advanced stage primary colorectal tumours exhibited an additional overexpression of theC6orf173gene (p<0.05).ConclusionsWe characterised two distinctive gene expression patterns to aid in the stratification of primary colorectal neoplasms among Malaysian patients with CRC. Further work can be done to assess and compare the mRNA expression levels of these identified DEGs between each CRC stage group, stages I–IV.
Protocol for a prospective, multicentre registry study of stenting for symptomatic intracranial artery stenosis in China
Authors: Wang Yilong , Miao Zhongrong , Wang Yongjun , Zhao Xingquan , Gao Peiyi , Liu Liping , Wang Feng , Liu Yajie , Ma Ning , Xu Ziqi , Mo, Dapeng , Gao Feng ,   China registry study group
Published: August 2014

IntroductionThe SAMMPRIS trial suggested that aggressive treatment was superior to endovascular stenting in patients with severe symptomatic intracranial atherosclerotic stenosis (ICAS) due to high complication rates in patients in the stenting group. Given that 12.2% patients failed aggressive medical therapy in the SAMMPRIS study, it is imperative to perform a multicentre prospective registry study of stenting for patients with ICAS in China. This study aims to evaluate the safety and efficacy of endovascular stenting for patients with symptomatic intracranial artery stenosis and poor collaterals in China and to identify the characteristics of the population that would benefit the most from endovascular stenting in Chinese patients.Methods and analysisThis multicentre prospective registry study will involve 20 stroke centres in China, and plans to recruit 300 patients into the registry. Patients with ≥70% stenosis and symptomatic intracranial atherosclerotic disease caused by hypoperfusion combined with poor collaterals who met the inclusion criteria and exclusion criteria would be enrolled for this study. The primary outcome is the target vessel stroke event (including haemorrhagic or ischaemic stroke) or death within 30 days after stenting. The secondary outcomes include the successful recanalisation rate, the incidence of recurrent ischaemic stroke in the territory of the stented artery between 30 days and 1 year postoperatively, the restenosis rate and health-related quality of life.Ethics and disseminationThe protocol is approved by the ethics committee at the coordinating centre and by the local institutional review board at each participating centre. Findings will be shared with participating hospitals, policymakers and the academic community to promote quality monitoring, quality improvement and the efficient allocation and use of cerebral catheterisation and intracranial artery stenting in China.Trial registration numberhttp://www.clinicaltrials.gov(NCT01968122).
Life course structural equation model of the effects of prenatal and postnatal growth on adult blood pressure
Authors: Kaakinen Marika , Sovio Ulla , Hartikainen Anna-Liisa , Pouta Anneli , Savolainen Markku J , Herzig Karl-Heinz , Elliott Paul , De Stavola Bianca , Läärä Esa , Järvelin Marjo-Riitta 
Published: August 2014

BackgroundFetal and postnatal growth have been associated with adult blood pressure (BP), but findings about the relative importance of growth at different stages of life on BP are inconsistent.MethodsThe study population comprised 5198 participants from the Northern Finland Birth Cohort 1966 with data on birth weight, height and weight measurements until adolescence, systolic and diastolic BP at 31 years and several covariates. Structural equation modelling was used in the analysis.ResultsNegative direct effects of birth weight on adult systolic BP were observed (standardised regression coefficients: −0.08 (−0.14 to −0.03) in males and −0.04 (−0.09 to 0.01) in females, equalling −1.99 (−3.32 to −0.65) and −1.01 (−2.33 to 0.32) mm Hg/kg, respectively). Immediate postnatal growth was associated with adult BP only indirectly via growth later in life. In contrast, growth from adiposity rebound onwards had large direct, indirect and total effects on adult BP. Current body mass index was the strongest growth-related predictor of adult BP (0.36 (0.30 to 0.41) in males and 0.31 (0.24, 0.37) in females, equalling 1.29 (1.09 to 1.48) and 0.81 (0.63 to 0.99) mm Hg/(kg/m2), respectively).ConclusionsOur path analytical approach provides evidence for the importance of both fetal growth and postnatal growth, especially from adiposity rebound onwards, in determining adult BP, together with genetic predisposition and behavioural factors.
Extreme temperatures and out-of-hospital coronary deaths in six large Chinese cities
Authors: Chen Renjie , Li Tiantian , Cai Jing , Yan Meilin , Zhao Zhuohui , Kan Haidong 
Published: August 2014

BackgroundThe seasonal trend of out-of-hospital coronary death (OHCD) and sudden cardiac death has been observed, but whether extreme temperature serves as a risk factor is rarely investigated. We therefore aimed to evaluate the impact of extreme temperatures on OHCDs in China. We obtained death records of 126 925 OHCDs from six large Chinese cities (Harbin, Beijing, Tianjin, Nanjing, Shanghai and Guangzhou) during the period 2009–2011.MethodsThe short-term associations between extreme temperature and OHCDs were analysed with time-series methods in each city, using generalised additive Poisson regression models. We specified distributed lag non-linear models in studying the delayed effects of extreme temperature. We then applied Bayesian hierarchical models to combine the city-specific effect estimates.ResultsThe associations between extreme temperature and OHCDs were almost U-shaped or J-shaped. The pooled relative risks (RRs) of extreme cold temperatures over the lags 0–14 days comparing the 1st and 25th centile temperatures were 1.49 (95% posterior interval (PI) 1.26–1.76); the pooled RRs of extreme hot temperatures comparing the 99th and 75th centile temperatures were 1.53 (95% PI 1.27–1.84) for OHCDs. The RRs of extreme temperature on OHCD were higher if the patients with coronary heart disease were old, male and less educated.ConclusionsThis multicity epidemiological study suggested that both extreme cold and hot temperatures posed significant risks on OHCDs, and might have important public health implications for the prevention of OHCD or sudden cardiac death.
Incidence and morbidity of craniocervical arterial dissections in atraumatic subarachnoid hemorrhage patients who underwent aneurysmal repair
Authors: Carr Kevin , Rincon Fred , Maltenfort Mitchell , Birnbaum Lee , Dengler Bradley , Rodriguez Michelle , Seifi Ali 
Published: August 2014

BackgroundNo studies have assessed the incidence of craniocervical arterial dissections (CCADs) and its association to mortality in hospitalized patients with a primary diagnosis of atraumatic subarachnoid hemorrhage (SAH) requiring aneurysmal repair. We hypothesize that the incidence of CCADs in these patients has increased over time as well as its association to mortality.MethodsWe conducted a 9 year retrospective assessment of the incidence of CCADs in patients hospitalized with a primary diagnosis of an SAH requiring repair and the effect of CCAD on mortality. Using the Nationwide Inpatient Sample (NIS), we queried records from 2003 to 2011 for an ICD-9 (International Classification of Diseases-9) code corresponding to admissions for atraumatic SAH. Demographical data, incidence of CCADs, type of aneurysmal repair, length of hospital stay, and hospital mortality were recorded. Multivariate logistical regression models were fitted to assess for the impact of CCAD on inhospital mortality and morbidity.ResultsDuring the period 2003–2011, of the NIS reported 18 260 patients who required aneurysmal SAH repair, 9737 (53.32%) underwent endovascular coiling and 8523 (46.48%) had surgical clipping. There were 131 patients in the cohort with reported CCADs: 94 (71.75%) of these patients had received endovascular coiling repair and 37 (28.25%) had undergone surgical clipping repair. Patients who underwent endovascular coiling had a higher rate of CCADs in this cohort (OR 2.94; 95% CI 2.00 to 4.31, p<0.0001). The incidence of CCADs in this population increased by an average rate of 9.4% per year (OR 1.14; 95% CI 1.06 to 1.23, p<0.0006), from 0.49% in 2003 to 1.10% in 2011. The diagnosis of CCAD added 3 and 6 more days to median length of hospitalization stay for surgical clipping and endovascular coiling, respectively. The unadjusted rate of mortality was 8.4% in the CCADs subgroup, and the presence of CCAD was not a predictor of mortality in our multivariate regression model (OR 0.68; 95% CI 0.36 to 1.27, p=0.2244).ConclusionsOur study indicates an annual increase in the incidence of CCADs in patients admitted with SAH who require aneurysmal repair. More than two-thirds of these patients that developed CCADs had undergone endovascular coiling repair. A diagnosis of CCAD increased the length of hospital stay but had no statistically significant association with mortality in this patient population.
Management of enterocutaneous fistula associated with an umbilical hernia in a two‐year‐old horse
Authors: Barba Marta , Barrett Elizabeth , Cesar Fernanda , Caldwell Fred , Schumacher John 
Published: August 2014

Enterocutaneous fistula (ECF) occurs when there is open communication between the lumen of intestine and the skin. This report describes a two‐year‐old, American Quarter Horse filly presented with an acute ECF involving the ileum entrapped within an umbilical hernia. After four days of conservative therapy and worsening of hydration status and electrolyte and acid‐base imbalances, surgical correction of the ECF was performed. The filly was stable 24 hours after surgery and eventually made a full recovery.