bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual Substrate Specificity of an
N
-Acetylglucosamine Phosphotransferase System in Clostridium beijerinckii
Authors: Al Makishah Naief H. , Mitchell Wilfrid J. 
Published: August 2013

ABSTRACT

The solventogenic clostridia have a considerable capacity to ferment carbohydrate substrates with the production of acetone and butanol, making them attractive organisms for the conversion of waste materials to valuable products. In common with other anaerobes, the clostridia show a marked dependence on the phosphoenolpyruvate (PEP)-dependent phosphotransferase system (PTS) to accumulate sugars and sugar derivatives. In this study, we demonstrate that extracts of
Clostridium beijerinckii
grown on
N
-acetylglucosamine (GlcNAc) exhibit PTS activity for the amino sugar. The PTS encoded by the divergent genes
cbe4532
(encoding the IIC and IIB domains) and
cbe4533
(encoding a IIA domain) was shown to transport and phosphorylate GlcNAc and also glucose. When the genes were recombined in series under the control of the
lac
promoter in pUC18 and transformed into a phosphotransferase mutant (
nagE
) of
Escherichia coli
lacking GlcNAc PTS activity, the ability to take up and ferment GlcNAc was restored, and extracts of the transformant showed PEP-dependent phosphorylation of GlcNAc. The gene products also complemented an
E. coli
mutant lacking glucose PTS activity but were unable to complement the same strain for PTS-dependent mannose utilization. Both GlcNAc and glucose induced the expression of
cbe4532
and
cbe4533
in
C. beijerinckii
, and consistent with this observation, extracts of cells grown on glucose exhibited PTS activity for GlcNAc, and glucose did not strongly repress utilization of GlcNAc by growing cells. On the basis of the phylogeny and function of the encoded PTS, we propose that the genes
cbe4532
and
cbe4533
should be designated
nagE
and
nagF
, respectively.
New Approaches Indicate Constant Viral Diversity despite Shifts in Assemblage Structure in an Australian Hypersaline Lake
Authors: Emerson Joanne B. , Thomas Brian C. , Andrade Karen , Heidelberg Karla B. , Banfield Jillian F. 
Published: August 2013

ABSTRACT
It is widely stated that viruses represent the most significant source of biodiversity on Earth, yet characterizing the diversity of viral assemblages in natural systems remains difficult. Viral diversity studies are challenging because viruses lack universally present, phylogenetically informative genes. Here, we developed an approach to estimate viral diversity using a series of functional and novel conserved genes. This approach provides direct estimates of viral assemblage diversity while retaining resolution at the level of individual viral populations in a natural system. We characterized viral assemblages in eight samples from hypersaline Lake Tyrrell (LT), Victoria, Australia, using 39,636 viral contigs. We defined viral operational taxonomic units (OTUs) in two ways. First, we used genes with three different functional predictions that were abundantly represented in the data set. Second, we clustered proteins of unknown function based on sequence similarity, and we chose genes represented by three clusters with numerous members to define OTUs. In combination, diversity metrics indicated between 412 and 735 sampled populations, and the number of populations remained relatively constant across samples. We determined the relative representation of each viral OTU in each sample and found that viral assemblage structures correlate with salinity and solution chemistry. LT viral assemblages were near-replicates from the same site sampled a few days apart but differed significantly on other spatial and temporal scales. The OTU definition approach proposed here paves the way for metagenomics-based analyses of viral assemblages using ecological models previously applied to bacteria and archaea.
Functional Genotyping of Sulfurospirillum spp. in Mixed Cultures Allowed the Identification of a New Tetrachloroethene Reductive Dehalogenase
Authors: Buttet Géraldine F. , Holliger Christof , Maillard Julien 
Published: August 2013

ABSTRACT

Reductive dehalogenases are the key enzymes involved in the anaerobic respiration of organohalides such as the widespread groundwater pollutant tetrachloroethene. The increasing number of available bacterial genomes and metagenomes gives access to hundreds of new putative reductive dehalogenase genes that display a high level of sequence diversity and for which substrate prediction remains very challenging. In this study, we present the development of a functional genotyping method targeting the diverse reductive dehalogenases present in
Sulfurospirillum
spp., which allowed us to unambiguously identify a new reductive dehalogenase from our tetrachloroethene-dechlorinating SL2 bacterial consortia. The new enzyme, named PceA
TCE
, shows 92% sequence identity with the well-characterized PceA enzyme of
Sulfurospirillum multivorans
, but in contrast to the latter, it is restricted to tetrachloroethene as a substrate. Its apparent higher dechlorinating activity with tetrachloroethene likely allowed its selection and maintenance in the bacterial consortia among other enzymes showing broader substrate ranges. The sequence-substrate relationships within tetrachloroethene reductive dehalogenases are also discussed.
Antimicrobial Tolerance of Pseudomonas aeruginosa Biofilms Is Activated during an Early Developmental Stage and Requires the Two-Component Hybrid SagS
Authors: Gupta Kajal , Marques Cláudia N. H. , Petrova Olga E. , Sauer Karin 
Published: August 2013

ABSTRACT

A hallmark characteristic of biofilms is their extraordinary tolerance to antimicrobial agents. While multiple factors are thought to contribute to the high level of antimicrobial tolerance of biofilms, little is known about the timing of induction of biofilm tolerance. Here, we asked when over the course of their development do biofilms gain their tolerance to antimicrobial agents? We demonstrate that in
Pseudomonas aeruginosa
, biofilm tolerance is linked to biofilm development, with transition to the irreversible attachment stage regulated by the two-component hybrid SagS, marking the timing when biofilms switch to the high-level tolerance phenotype. Inactivation of
sagS
rendered biofilms but not planktonic cells more susceptible to tobramycin, norfloxacin, and hydrogen peroxide. Moreover, inactivation of
sagS
also eliminated the recalcitrance of biofilms to killing by bactericidal antimicrobial agents, a phenotype comparable to that observed upon inactivation of
brlR
, which encodes a MerR-like transcriptional regulator required for biofilm tolerance. Multicopy expression of
brlR
in a Δ
sagS
mutant restored biofilm resistance and recalcitrance to killing by bactericidal antibiotics to wild-type levels. In contrast, expression of
sagS
did not restore the susceptibility phenotype of Δ
brlR
mutant biofilms to wild-type levels, indicating that BrlR functions downstream of SagS. Inactivation of
sagS
correlated with reduced BrlR levels in biofilms, with the produced BrlR being impaired in binding to the previously described BrlR-activated promoters of the two multidrug efflux pump operons
mexAB-oprM
and
mexEF-oprN
. Our findings demonstrate that biofilm tolerance is linked to early biofilm development and SagS, with SagS contributing indirectly to BrlR activation.
miR-200b and miR-200c as Prognostic Factors and Mediators of Gastric Cancer Cell Progression
Authors: Tang Hailin , Deng Min , Tang Yunyun , Xie Xinhua , Guo Jiaoli , Kong Yanan , Ye Feng , Su Qi , Xie Xiaoming 
Published: August 2013

Abstract
Purpose: The purpose of this study was to investigate the clinicopathologic significance and potential role of miR-200b and miR-200c in the development and progression of gastric cancer.
Experimental Design: We examined miR-200b and miR-200c expression in 36 paired normal and stomach tumor specimens, as well as gastric cancer cell lines, by quantitative real-time PCR. In addition, miR-200b and miR-200c were detected by ISH using gastric cancer tissue microarrays, and the association between miR-200b and miR-200c levels and clinicopathologic factors and prognosis were analyzed. A luciferase assay was conducted for target evaluation. The functional effects of miR-200b and miR-200c on gastric cancer cells were validated by a cell proliferation assay and cell invasion and migration assays.
Results: miR-200b and miR-200c were downregulated in the gastric cancer specimens and cell lines tested. miR-200b and miR-200c levels were significantly correlated with the clinical stage, T stage, lymph node metastasis, and survival of patients. Ectopic expression of miR-200b and miR-200c impaired cell growth and invasion. In addition, when overexpressed, miR-200b and miR-200c commonly directly targeted DNMT3A, DNMT3B, and SP1 (a transactivator of the DNMT1 gene), which resulted in marked reduction of the expression of DNA methyltransferases DNMT1, DNMT3A, and DNMT3B at the protein level. This effect, in turn, led to a decrease in global DNA methylation and reexpression of p16, RASS1A1, and E-cadherin via promoter DNA hypomethylation.
Conclusion: Our findings suggest that miR-200b and miR-200c, as valuable markers of gastric cancer prognosis, may be a promising approach to human gastric cancer treatment. Clin Cancer Res; 19(20); 5602–12. ©2013 AACR.
Koch Institute Symposium on Cancer Immunology and Immunotherapy
Authors: Drake Adam , Joshi Nikhil S. , Szeto Gregory L. , Zhu Eric F. , Eisen Herman N. , Irvine Darrell J. 
Published: August 2013

Abstract
The 12th annual summer symposium of The Koch Institute for Integrative Cancer Research at MIT was held in Cambridge, Massachusetts, on June 14, 2013. The symposium, entitled “Cancer Immunology and Immunotherapy,” focused on recent advances in preclinical research in basic immunology and biomedical engineering and their clinical application in cancer therapies. The day-long gathering also provided a forum for discussion and potential collaborations between engineers and clinical investigators. The major topics presented included (i) enhancement of adoptive cell therapy by engineering to improve the ability and functionality of T cells against tumor cells; (ii) current therapies using protein and antibody therapeutics to modulate endogenous antitumor immunity; and (iii) new technologies to identify molecular targets and assess therapeutic efficacy, and devices to control and target drug delivery more effectively and efficiently. Cancer Immunol Res; 1(4); 217–22. ©2013 AACR.
Activity Intensity During Free-Living Activities in Children and Adolescents With Inherited Arrhythmia Syndromes
Authors: Gow Robert M. , Borghese Michael M. , Honeywell Christina R. , Colley Rachel C. 
Published: August 2013

Background—
International guidelines recommend restriction of activities for many children and adolescents with inherited arrhythmia syndromes to moderate activity (<7 metabolic equivalents [METs]). We hypothesized that moderate levels of intensity would be exceeded during free-living daily activity in these individuals when assessed objectively by combined heart rate and accelerometry monitor (Actiheart).

Methods and Results—

Participants wore the Actiheart for ≤7 days on 2 occasions after a maximal exercise test that was used to calibrate the monitor individually against intensity levels. Of 16 participants, 13 (81%) had long QT syndrome, 9 (56%) were female, and median age was 12 years. Monitors were worn for a median (range) of 13 (6–14) days, and a mean (SD) of 11.3 (1.7) hours per day. Vigorous (7 MET) and very vigorous (10 MET) thresholds were exceeded by 15 and 13 participants, respectively. The median (interquartile range), individual, total weekly time spent >7 MET threshold was 113 (65–330) minutes, whereas such time spent >10 MET threshold was 53 (9–115) minutes. Total time >7 MET threshold was 2.3% of monitor wear time. There were no differences in time above threshold between male and female participants (
P
=0.357) or among those with different levels of activity restriction (
P
=0.769).

Conclusions—
Current recommended activity guidelines are frequently exceeded during routine free-living activities in young participants with inherited arrhythmia syndromes. Whether this indicates increased risk for these individuals or excessively restrictive guidelines remains to be determined.
Impact of QRS Morphology and Duration on Outcomes After Cardiac Resynchronization Therapy
Authors: Birnie David H. , Ha Andrew , Higginson Lyall , Sidhu Kiran , Green Martin , Philippon François , Thibault Bernard , Wells George , Tang Anthony 
Published: August 2013

Background—
The impact of QRS morphology and duration on the effectiveness of cardiac resynchronization therapy (CRT) has been usually assessed separately. The interaction between these 2 simple ECG parameters and their effect on CRT has not been systematically assessed in a large-scale clinical trial.

Methods and Results—

The Resynchronization–Defibrillation for Ambulatory Heart Failure Trial showed that implantable cardioverter defibrillator-CRT was associated with a significant reduction in the primary end point of all-cause mortality or heart failure hospitalization. For this substudy, we excluded patients in atrial fibrillation and those with a previous pacemaker. All baseline ECGs were reviewed by a panel of 3 experienced electrocardiographers. A total of 1483 patients were included in this study. Of these, 1175 had left bundle-branch block (LBBB) and 308 had non-LBBB. In patients with LBBB receiving implantable cardioverter defibrillator-CRT, there was a reduction in the primary outcome and in each individual component of the primary outcome. Furthermore, there was continuous relationship between QRS duration and extent of benefit. In patients with non-LBBB and QRS ≥160 ms, the hazard ratio for the primary outcome was 0.52 (0.29–0.96;
P
=0.033); in patients with QRS <160 ms, the hazard ratio was 1.38 (0.88–2.14;
P
=0.155).

Conclusions—
In patients with LBBB, there was a continuous relationship between broader QRS and greater benefit from implantable cardioverter defibrillator-CRT. However, our data do not support the use of implantable cardioverter defibrillator-CRT in patients with non-LBBB, especially when the QRS duration is <160 ms. There may be some delayed benefit when the QRS is ≥160 ms, but this needs further investigation.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00251251.
Complexity or meaning in health professional education and practice?
Authors: Lowe Wendy Anne 
Published: August 2013

Objectives: Discourses of complexity have entered health professional education. This paper explores the meaning of complexity by asking how health professionals are educated and some of the consequences of that education. Design: A qualitative study was carried out drawing on reflexivity, discourse analysis and grounded methodology. Setting: Two rural healthcare settings in Western Australia. Methods: Seventeen health professionals were interviewed using semi-structured open-ended questions based on a theoretical framework developed from the analysis of three case studies of education in healthcare practice. The interview responses were transcribed then analysed. Themes were identified using an iterative process of reflexivity. Narratives of health professional identity were explored within the context of health professional education. Results: The responses from the participants indicated that they managed discourses of autonomy, control and empowerment alongside their own narratives of passivity and powerlessness. Management of different discourses seemed to make other discourses recede. For example, reference to broader issues such as race, gender, ethnicity, socioeconomic determinants of health and age were minimal. Conclusions: Health professional education discourses could be seen as obscuring broader issues that impact on healthcare practice. Health professional curricula occupy a privileged location within society and as such need to provide a socially accountable practice. Ways to develop socially accountable practices are explored within the context of the widening gap between disadvantaged and advantaged people on a global level.
Political Economy of the Telugu Film Industry
Authors: Shaw Padmaja 
Published: September 2013

India has the distinction of being one of the largest producers of films. The Telugu film industry is the second largest in India, sometimes producing more number of films than the Hindi film industry. However, there has been a serious dearth of ‘good cinema’, as evidenced by the absence of National Awards in the Telugu language category over the last several years. The analysis in this article is based on the assumption that alternative perspectives find space even within the capitalist mode of production when contradictory pressures of class interests operate. In the cultural industries, the intellectuals—both bourgeois and progressive—are jostling for space. In this struggle, there are class contradictions within the cultural industries, which enable the progressive intellectual to play a visible role, even though it is not a dominant one. The near complete absence of such spaces and processes is the subject of this analysis. This article examines the practices within the Telugu film industry and attempts to identify the barriers to creativity and new talent using Marxian analysis. The study comes to the broad conclusion that given the social totality of Telugu society, a better regulatory environment could make a difference.
Predictors of the length of stay in a psychiatric emergency care centre
Authors: Brakoulias Vlasios , Seymour Joanne , Lee Jane , Sammut Peter , Starcevic Vladan 
Published: August 2013

Objective: This paper aims to ascertain predictors of the length of stay in a Psychiatric Emergency Care Centre (PECC). Methods: Demographic and clinical characteristics were recorded retrospectively via file audit in 477 patients who were admitted to a PECC within a six-month period. Associations between these variables and length of stay were analysed using logistic regression. Results: Length of stay in the PECC was predicted by medical complications arising in the PECC, absconding behaviour, diagnosis of depression and being brought in by family members. Aggression within the PECC and previous contact with mental health services predicted a shorter stay. Conclusions: Length of stay in the PECC is predicted by a number of variables that are different from those that predict length of stay in an acute psychiatric unit. A comprehensive assessment of these variables prior to admission may decrease the length of stay in the PECC and improve efficiency of acute psychiatric services.
Feline CKD
Authors: Reynolds Brice S , Lefebvre Hervé P 
Published: September 2013

Practical relevance: Chronic kidney disease (CKD) is one of the most frequently encountered disorders in cats, having increased in prevalence in recent decades. Although the underlying cause is rarely identified, the common final outcome of feline CKD is tubulointerstitial fibrosis. Knowledge of CKD pathophysiology is necessary for optimal individualised patient management, especially with regard to diagnosis and treatment of extrarenal complications. Patient group: CKD is most common in senior and geriatric cats, but should be considered in any feline patient with ureterolithiasis, hyperthyroidism, retrovirus infection, systemic hypertension, cardiovascular disease or urinary tract infection. Evidence base: Most of our knowledge of the pathogenesis of CKD is extrapolated from human nephrology and experimental animal studies. There is, therefore, a need for further studies in cats. The prevalence of clinical signs in feline CKD is well documented. Several concurrent diseases associated with CKD have also been reported in cats, especially in the geriatric population, but there is no or only limited published evidence demonstrating a cause-and-effect relationship between most of these conditions and CKD. Studies performed over the past 15 years have nevertheless allowed identification of major risk factors (proteinuria, plasma phosphate and plasma creatinine) influencing the progression of feline CKD. Clinical challenges: Clinical signs occur in the late stages of renal disease, so populations at higher risk of CKD should be screened routinely. CKD-associated complications (systemic hypertension, secondary renal hyperparathyroidism, hypokalaemia, anaemia, metabolic acidosis) must not be overlooked as they may affect the progression of disease. Disease progression is itself unpredictable and renal function may remain stable for extended periods. Most cats with early CKD do not progress to end-stage CKD before they die. Audience: General practitioners play a major role in screening feline patients at risk of development or progression of CKD.
Feline CKD
Authors: Korman Rachel M , White Joanna D 
Published: September 2013

Practical relevance: Treatment of feline chronic kidney disease (CKD) tends to focus on minimising the adverse effects of reduced renal function, rather than addressing an underlying cause. Despite this, and the progressive nature of CKD, treatment can improve quality of life and enable many cats to have long survival times. Evidence base: Strong evidence supports the provision of renal diets, which are protein and phosphorus restricted; compliance is improved by gradual dietary transition. Additional phosphorus restriction is achieved by the use of phosphate binding agents, although it is unknown if these yield similar survival benefits to those provided by renal diets. Interventions to control hypokalaemia and hypertension in affected cats are important to prevent serious complications. Administration of benazepril to cats with proteinuric kidney disease has been shown to significantly improve their appetite but not their survival. As CKD progresses, many cats will benefit from treatment to control clinical signs of uraemic gastroenteritis and anaemia.
Feline CKD
Authors: Taylor Samantha , Sparkes Andrew H 
Published: September 2013

Practical relevance: Chronic kidney disease (CKD) is common in humans as well as in cats, and is a significant human health problem. In feline medicine, despite recent research and improvements in our understanding of the condition, management remains limited by late diagnosis and an inadequate ability to prevent progression of disease. Investigation of future treatments that both delay the progression of CKD and manage clinical signs, and that are also easy and cost effective to administer, is desirable. To this end, we may learn from our colleagues in the medical profession. Audience: CKD is commonly encountered in general practice and so all practitioners dealing with cats will benefit from understanding future treatment possibilities and interventions in the management of CKD. Evidence base: Large-scale medical studies have been performed to provide an evidence base for treatment decisions in human CKD. Several studies in cats have looked at various aspects of treatment and prognosis, but large-scale studies are needed to assess the benefits of treatments such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Clinical challenges: Providing treatment that is effective, easy to administer and not cost-prohibitive is the challenge currently faced by clinicians in the management of feline CKD.