bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stress‐dependent hypertension and the role of T lymphocytes
Authors: Marvar Paul J. , Harrison David G. 
Published: September 2012

Hypertension is a significant global health burden that is associated with an increased risk of stroke, atherosclerosis and other cardiovascular diseases. Several risk factors, including high dietary salt, obesity, genetics and race, as well as behavioural and psychological factors, contribute to development of this complex disease. Various hypertensive stimuli enhance sympathetic drive and promote autonomic dysfunction leading to elevated blood pressure. As our understanding of the pathogenesis and end‐organ damage associated with hypertension increases, mounting evidence also highlights the role of inflammation in this process and, in particular, the role of the adaptive immune system and T cells. This review discusses recent findings regarding the role of the central nervous system, T lymphocytes and the impact of cardiovascular risk factors, such as psychological stress, in hypertension.
The regulation of interleukin‐6 implicates skeletal muscle as an integrative stress sensor and endocrine organ
Authors: Welc Steven S. , Clanton Thomas L. 
Published: September 2012

New findings
What is the topic of this review?This review discusses the regulation of the interleukin‐6 (IL‐6) gene and how it is uniquely set up to respond to stress signals in skeletal muscle. We propose that skeletal muscle is a ‘stress sensor’ that responds by releasing highly active endocrine and paracrine proteins, such as IL‐6.
What advances does this highlight?Recent discoveries on the regulation of the IL‐6 gene in various stress exposures have resulted in the emergence of a new potential role for skeletal muscle in life‐threatening stress conditions. Understanding the relationship between IL‐6 secretion and stress may provide new insights into normal adaptive responses to disease, deconditioning, inflammation and ageing.
Skeletal muscle has been identified as an endocrine organ owing to its capacity to produce and secrete a variety of cytokines (myokines) and other proteins. To date, myokines have primarily been studied in response to exercise or metabolic challenges; however, numerous observations suggest that skeletal muscle may also release myokines in response to certain categories of internal or external stress exposure. Internal stress signals include oxidative or nitrosative stress, damaged or unfolded proteins, hyperthermia or energy imbalance. External stress signals, which act as indicators of organismal stress or injury in other cells, employ mediators such as catecholamines, endotoxin, alarmins, ATP and pro‐inflammatory cytokines, such as tumour necrosis factor‐α and interleukin‐1β. External stress signals generally induce cellular responses through membrane receptor systems. In this review, we focus on the regulation of interleukin‐6 (IL‐6) as a prototypical stress response myokine and highlight evidence that IL‐6 gene regulation in muscle is inherently organized to respond to a wide variety of internal and external stressors. Given that IL‐6 can initiate protective, anti‐inflammatory or restorative processes throughout the organism during life‐threatening conditions, we present the argument that skeletal muscle has a physiological function as a sensor and responder to stress. Furthermore, we hypothesize that it may comprise a fundamental component of the organism's acute stress response.
Synthetic Pathway for Production of Five-Carbon Alcohols from Isopentenyl Diphosphate
Authors: Chou Howard H. , Keasling Jay D. 
Published: September 2012

ABSTRACT
Synthetic biological pathways could enhance the development of novel processes to produce chemicals from renewable resources. On the basis of models that describe the evolution of metabolic pathways and enzymes in nature, we developed a framework to rationally identify enzymes able to catalyze reactions on new substrates that overcomes one of the major bottlenecks in the assembly of a synthetic biological pathway. We verified the framework by implementing a pathway with two novel enzymatic reactions to convert isopentenyl diphosphate into 3-methyl-3-butenol, 3-methyl-2-butenol, and 3-methylbutanol. To overcome competition with native pathways that share the same substrate, we engineered two bifunctional enzymes that redirect metabolic flux toward the synthetic pathway. Taken together, our work demonstrates a new approach to the engineering of novel synthetic pathways in the cell.
Enhancement of Ganoderic Acid Accumulation by Overexpression of an N-Terminally Truncated 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Gene in the Basidiomycete Ganoderma lucidum
Authors: Xu Jun-Wei , Xu Yi-Ning , Zhong Jian-Jiang 
Published: September 2012

ABSTRACTGanoderic acids produced byGanoderma lucidum, a well-known traditional Chinese medicinal mushroom, exhibit antitumor and antimetastasis activities. Genetic modification ofG. lucidumis difficult but critical for the enhancement of cellular accumulation of ganoderic acids. In this study, a homologous genetic transformation system forG. lucidumwas developed for the first time using mutatedsdhB, encoding the iron-sulfur protein subunit of succinate dehydrogenase, as a selection marker. The truncatedG. lucidumgene encoding the catalytic domain of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) was overexpressed by using theAgrobacterium tumefaciens-mediated transformation system. The results showed that the mutatedsdhBsuccessfully conferred carboxin resistance upon transformation. Most of the integrated transfer DNA (T-DNA) appeared as a single copy in the genome. Moreover, deregulated constitutive overexpression of the HMGR gene led to a 2-fold increase in ganoderic acid content. It also increased the accumulation of intermediates (squalene and lanosterol) and the upregulation of downstream genes such as those of farnesyl pyrophosphate synthase, squalene synthase, and lanosterol synthase. This study demonstrates that transgenic basidiomyceteG. lucidumis a promising system to achieve metabolic engineering of the ganoderic acid pathway.
Proteorhodopsin-Like Genes Present in Thermoacidophilic High-Mountain Microbial Communities
Authors: Bohorquez Laura C. , Ruiz-Pérez Carlos A. , Zambrano María Mercedes 
Published: September 2012

ABSTRACTProteorhodopsin (PR) sequences were PCR amplified from three Andean acidic hot spring samples. These sequences were similar to freshwater and marine PRs and they contained residues indicative of proton-pumping activity and of proteins that absorb green light; these findings suggest that PRs might contribute to cellular metabolism in these habitats.
AidC, a Novel
N
-Acylhomoserine Lactonase from the Potato Root-Associated Cytophaga-Flavobacteria-Bacteroides (CFB) Group Bacterium Chryseobacterium sp. Strain StRB126
Authors: Wang Wen-Zhao , Morohoshi Tomohiro , Someya Nobutaka , Ikeda Tsukasa 
Published: September 2012

ABSTRACT

N
-Acylhomoserine lactones (AHLs) are used as quorum-sensing (QS) signal molecules by many Gram-negative bacteria. We have reported that
Chryseobacterium
sp. strain StRB126, which was isolated from the root surface of potato, has AHL-degrading activity. In this study, we cloned and characterized the
aidC
gene from the genomic library of StRB126. AidC has AHL-degrading activity and shows homology to several metallo-β-lactamase proteins from
Bacteroidetes
, although not to any known AHL-degrading enzymes. Purified AidC, as a maltose-binding fusion protein, showed high degrading activity against all tested AHLs, whether short- or long-chain forms, with or without substitution at carbon 3. High-performance liquid chromatography (HPLC) analysis revealed that AidC functions as an AHL lactonase catalyzing AHL ring opening by hydrolyzing lactones. An assay to determine the effects of covalent and ionic bonding showed that Zn
2+
is important to AidC activity both
in vitro
and
in viv
o. In addition, the
aidC
gene could also be PCR amplified from several other
Chryseobacterium
strains. In conclusion, this study indicated that the
aidC
gene, encoding a novel AHL lactonase, may be widespread throughout the genus
Chryseobacterium
. Our results extend the diversity and known bacterial hosts of AHL-degrading enzymes.
Abundance and Genetic Diversity of
nifH
Gene Sequences in Anthropogenically Affected Brazilian Mangrove Sediments
Authors: Dias Armando Cavalcante Franco , Pereira e Silva Michele de Cassia , Cotta Simone Raposo , Dini-Andreote Francisco , Soares Fábio Lino , Salles Joana Falcão , Azevedo João Lúcio , van Elsas Jan Dirk , Andreote Fernando Dini 
Published: September 2012

ABSTRACT

Although mangroves represent ecosystems of global importance, the genetic diversity and abundance of functional genes that are key to their functioning scarcely have been explored. Here, we present a survey based on the
nifH
gene across transects of sediments of two mangrove systems located along the coast line of São Paulo state (Brazil) which differed by degree of disturbance, i.e., an oil-spill-affected and an unaffected mangrove. The diazotrophic communities were assessed by denaturing gradient gel electrophoresis (DGGE), quantitative PCR (qPCR), and clone libraries. The
nifH
gene abundance was similar across the two mangrove sediment systems, as evidenced by qPCR. However, the
nifH
-based PCR-DGGE profiles revealed clear differences between the mangroves. Moreover, shifts in the
nifH
gene diversities were noted along the land-sea transect within the previously oiled mangrove. The
nifH
gene diversity depicted the presence of nitrogen-fixing bacteria affiliated with a wide range of taxa, encompassing members of the
Alphaproteobacteria
,
Betaproteobacteria
,
Gammaproteobacteria
,
Firmicutes
, and also a group of anaerobic sulfate-reducing bacteria. We also detected a unique mangrove-specific cluster of sequences denoted Mgv-
nifH
. Our results indicate that nitrogen-fixing bacterial guilds can be partially endemic to mangroves, and these communities are modulated by oil contamination, which has important implications for conservation strategies.
Mechanisms for Photoinactivation of Enterococcus faecalis in Seawater
Authors: Sassoubre Lauren M. , Nelson Kara L. , Boehm Alexandria B. 
Published: September 2012

ABSTRACT

Field studies in fresh and marine waters consistently show diel fluctuations in concentrations of enterococci, indicators of water quality. We investigated sunlight inactivation of
Enterococcus faecalis
to gain insight into photoinactivation mechanisms and cellular responses to photostress.
E. faecalis
bacteria were exposed to natural sunlight in clear, filtered seawater under both oxic and anoxic conditions to test the relative importance of oxygen-mediated and non-oxygen-mediated photoinactivation mechanisms. Multiple methods were used to assess changes in bacterial concentration, including cultivation, quantitative PCR (qPCR), propidium monoazide (PMA)-qPCR, LIVE/DEAD staining using propidium iodide (PI), and cellular activity, including ATP concentrations and expression of the superoxide dismutase-encoding gene,
sodA
. Photoinactivation, based on numbers of cultivable cells, was faster in oxic than in anoxic microcosms exposed to sunlight, suggesting that oxygen-mediated photoinactivation dominated. There was little change in qPCR signal over the course of the experiment, demonstrating that the nucleic acid targets were not damaged to a significant extent. The PMA-qPCR signal was also fairly stable, consistent with the observation that the fraction of PI-permeable cells was constant. Thus, damage to the membrane was minimal. Microbial ATP concentrations decreased in all microcosms, particularly the sunlit oxic microcosms. The increase in relative expression of the
sodA
gene in the sunlit oxic microcosms suggests that cells were actively responding to oxidative stress. Dark repair was not observed. This research furthers our understanding of photoinactivation mechanisms and the conditions under which diel fluctuations in enterococci can be expected in natural and engineered systems.
Small Multidrug Resistance Protein EmrE Reduces Host pH and Osmotic Tolerance to Metabolic Quaternary Cation Osmoprotectants
Authors: Bay Denice C. , Turner Raymond J. 
Published: September 2012

ABSTRACT

The small multidrug resistance (SMR) transporter protein EmrE in
Escherichia coli
is known to confer resistance to toxic antiseptics classified as quaternary cation compounds (QCCs). Naturally derived QCCs synthesized during metabolic activities often act as osmoprotectants, such as betaine and choline, and participate in osmotic homoestasis. The goal of this study was to determine if EmrE proteins transport biological QCC-based osmoprotectants. Plasmid-encoded copies of
E. coli
emrE
and the inactive variant
emrE
-E14C (
emrE
with the E→C change at position 14) were expressed in various
E. coli
strains grown in either rich or minimal media at various pHs (5 to 9) and under hypersaline (0.5 to 1.0 M NaCl and KCl) conditions to identify changes in growth phenotypes induced by osmoprotectant transport. The results demonstrated that
emrE
expression reduced pH tolerance of
E. coli
strains at or above neutral pH and when grown in hypersaline media at or above NaCl or KCl concentrations of 0.75 M. Hypersaline growth conditions were used to screen QCC osmoprotectants betaine, choline,
l
-carnitine,
l
-lysine,
l
-proline, and
l
-arginine. The study identified that betaine and choline are natural QCC substrates of EmrE.
Noncoding RNAs Binding to the Nucleoid Protein HU in Escherichia coli
Authors: Macvanin Mirjana , Edgar Rotem , Cui Feng , Trostel Andrei , Zhurkin Victor , Adhya Sankar 
Published: September 2012

ABSTRACT

Some unidentified RNA molecules, together with the nucleoid protein HU, were suggested to be involved in the nucleoid structure of
Escherichia coli
. HU is a conserved protein known for its role in binding to DNA and maintaining negative supercoils in the latter. HU also binds to a few RNAs, but the full spectrum of its binding targets in the cell is not known. To understand any interaction of HU with RNA in the nucleoid structure, we immunoprecipitated potential HU-RNA complexes from cells and examined bound RNAs by hybridization to whole-genome tiling arrays. We identified associations between HU and 10 new intragenic and intergenic noncoding RNAs (ncRNAs), 2 of which are homologous to the annotated bacterial interspersed mosaic elements (BIMEs) and
boxC
DNA repeat elements. We confirmed direct binding of HU to BIME RNA
in vitro
. We also studied the nucleoid shape of HU and two of the ncRNA mutants (nc1 and nc5) by transmission electron microscopy and showed that both HU and the two ncRNAs play a role in nucleoid morphology. We propose that at least two of the ncRNA species complex with HU and help the formation or maintenance of the architecture of the
E. coli
chromosome. We also observed binding of HU with rRNA and tRNA segments, a few small RNAs, and a distinct small set of mRNAs, although the significance, if any, of these associations is not known.
Injury in elite New Zealand cricketers 2002–2008: descriptive epidemiology
Authors: Frost Warren Leonard , Chalmers David John 
Published: September 2012

ObjectiveTo describe the incidence, prevalence, nature and severity of injury to elite New Zealand cricketers for the 2002/2003 to 2007/2008 seasons.DesignProspective cohort.SettingElite cricket in New Zealand.Participants248 elite male cricketers.Main outcome measuresIncidence and prevalence rates.ResultsThe overall match injury incidence rate for the international competition (51.6 injuries per 10 000 player-hours; 95% CI 40.1 to 65.3) was almost twice that of the domestic competition (27.2; 23.5 to 31.4). The prevalence rate for the international competition (12%; 11.3% to 12.8%) was significantly higher than that for the domestic competition (9.7%; 9.4% to 10.1%). Overall, 79.5% of injuries occurred in matches and 48.7% of all injuries were sustained while bowling. The lower limb was the body region most commonly injured (43.5%), the most common specific diagnosis was hamstring strains/tears (11.1%) and the injuries contributing the highest proportion of match days lost were stress fractures to the low back (22%).ConclusionsThe findings of this study support ongoing injury surveillance in New Zealand and other test cricket playing nations for the purpose of describing injury and monitoring the effect of interventions over time.
What happens to clinical training fellows? A retrospective study of the 20 years outcome of a Medical Research Council UK cohort
Authors: Stewart Paul M , Bryan Simone , Dukes Peter , van Oudheusden Hannah Lesley , Walker Rhoswyn , Maxwell Patrick H 
Published: August 2012

ObjectivesThe Clinical Research Training Fellowship (CRTF) allows up to 3 years support for clinically qualified candidates to undertake specialised or further research training in biomedical sciences. CRTFs are perceived as a crucial step in the career development and progression of Clinical Academics but there are no published data to support this notion. We conducted an electronic survey of a large cohort of Medical Research Council (MRC) CRTFs followed for up to 20 years.DesignRetrospective analysis of CRTF outcome data held with the MRC, UK.ParticipantsTwo cohorts comprising 40 CRFTs awarded by the MRC in the year 1991 and 299 MRC CRTFs who were awarded a fellowship between 1993 and 2003.ResultsThe MRC CRTF scheme built capacity in clinical academia across the UK with 40% of CRTFs progressing to a University professorship. Importantly, the CRTF scheme is also providing NHS consultants who remain research active.ConclusionsThis is the first analysis of outcome of CRTFs in the UK and provides robust evidence of the importance of this capacity building mode of funding to underpin research excellence at the University–NHS interface.
Venous sinus manometry and intervention using the PrimeWire Prestige pressure guidewire: technique and initial experience
Authors: Lopes Demetrius Klee , Johnson Andrew Kelly , Tan Lee A 
Published: September 2012

BackgroundCerebral venography and manometry are used for the diagnosis of hemodynamically significant venous sinus stenosis in patients with the syndrome of idiopathic intracranial hypertension. Intravenous pressure measurements using the traditional microcatheter technique can be cumbersome, time consuming and potentially unreliable. The PrimeWire Prestige pressure guidewire conducts pressure electrically and can be used as a guidewire for intervention. It has been validated in interventional cardiology procedures.ObjectiveWe describe our initial clinical experience with the PrimeWire Prestige pressure guidewire system for cerebral venous manometry and intervention.MethodCerebral venous pressure gradient was directly measured by advancing the pressure wire across a region of stenosis. The pressure wire was also used as a guidewire for intravascular ultrasound, angioplasty and stenting.ResultsThe PrimeWire Prestige pressure guidewire successfully navigated the intracranial venous sinus anatomy. Transfer of devices over the guidewire in a monorail fashion was uncomplicated, and measurement of sinus pressure between the steps of the intervention was efficiently performed.ConclusionThe PrimeWire Prestige pressure guidewire system provided a safe, fast and effective method for intracranial venous sinus manometry and intervention. It has several potential advantages over the traditional microcatheter method, including efficiency, accuracy and cost.
ROCK1 and ROCK2 Are Required for Non-Small Cell Lung Cancer Anchorage-Independent Growth and Invasion
Authors: Vigil Dominico , Kim Tai Young , Plachco Ana , Garton Andrew J. , Castaldo Linda , Pachter Jonathan A. , Dong Hanqing , Chen Xin , Tokar Brianna , Campbell Sharon L. , Der Channing J. 
Published: September 2012

Abstract
Evidence is emerging that the closely related ROCK1 and ROCK2 serine/threonine kinases support the invasive and metastatic growth of a spectrum of human cancer types. Therefore, inhibitors of ROCK are under preclinical development. However, a key step in their development involves the identification of genetic biomarkers that will predict ROCK inhibitor antitumor activity. One identified mechanism for ROCK activation in cancer involves the loss of function of the DLC1 tumor suppressor gene, which encodes a GTPase activating protein (RhoGAP) for the RhoA and RhoC small GTPases. DLC-1 loss may lead to hyperactivation of RhoA/C and its downstream effectors, the ROCK kinases. We therefore determined whether loss of DLC-1 protein expression identifies non-small cell lung carcinoma (NSCLC) cell lines whose growth and invasion phenotypes are sensitive to ROCK inhibition. We identified and characterized a novel small molecule pharmacologic inhibitor of ROCK and additionally applied genetic approaches to impair ROCK1 and/or ROCK2 activity, and we determined that although NSCLC anchorage-dependent growth was ROCK-independent, both anchorage-independent growth and Matrigel invasion were ROCK-dependent. However, loss of DLC-1 expression did not correlate with ROCK activation or with OXA-06 sensitivity. Unexpectedly, suppression of ROCK1 or ROCK2 expression alone was sufficient to impair anchorage-independent growth, supporting their nonoverlapping roles in oncogenesis. Mechanistically, the block in anchorage-independent growth was associated with accumulation of cells in the G0–G1 phase of the cell cycle, but not increased anoikis. We conclude that ROCK may be a useful therapeutic target for NSCLC. Cancer Res; 72(20); 5338–47. ©2012 AACR.
IKK-ϵ Coordinates Invasion and Metastasis of Ovarian Cancer
Authors: Hsu Sarah , Kim Marianne , Hernandez Lidia , Grajales Valentina , Noonan Anne , Anver Miriam , Davidson Ben , Annunziata Christina M. 
Published: September 2012

Abstract
Inhibitor of IκB kinases (IKK) are key regulators of NF-κB signaling. Three IKK isoforms—α, β, and ϵ—have been linked to oncogenesis, yet the precise components of NF-κB signaling in ovarian cancer have not yet been dissected. We surveyed 120 ovarian cancer specimens for IKK-ϵ expression. Notably, cytoplasmic expression was elevated in metastatic lesions relative to primary tumors (P = 0.03). Therefore, we hypothesized that IKK-ϵ drives ovarian cancer metastasis. IKK-ϵ was identified previously as a breast cancer oncogene and was associated with poor clinical outcome in ovarian cancer. We now define an ovarian cancer–specific IKK-ϵ–regulated gene expression signature using stably expressed short hairpin RNA targeting IKK-ϵ. Pathway analysis of the signature indicated that IKK-ϵ regulates expression of genes involved in cell motility and inflammation. We further showed that IKK-ϵ depletion in metastatic ovarian cancer cell lines decreased growth, adhesion, and invasion. Consistently, human xenografts depleted of IKK-ϵ in mice showed decreased aggressiveness, whereas overexpression of IKK-ϵ in a less invasive ovarian cancer cell line increased metastasis in vivo. Taken together, these data provide evidence that IKK-ϵ is a key coordinator of invasion and metastasis programs in ovarian cancer. Inhibition of IKK-ϵ signaling thus emerges as a viable therapeutic strategy in women whose ovarian cancer shows aberrant activation of this pathway. Cancer Res; 72(21); 5494–504. ©2012 AACR.