bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional genomics of dichloromethane utilization in Methylobacterium extorquens DM4
Authors: Muller Emilie E. L. , Hourcade Edith , Louhichi‐Jelail Yousra , Hammann Philippe , Vuilleumier Stéphane , Bringel Françoise 
Published: August 2011

SummaryDichloromethane (CH2Cl2, DCM) is a chlorinated solvent mainly produced by industry, and a common pollutant. Some aerobic methylotrophic bacteria are able to grow with this chlorinated methane as their sole carbon and energy source, using a DCM dehalogenase/glutathione S‐transferase encoded by dcmA to transform DCM into two molecules of HCl and one molecule of formaldehyde, a toxic intermediate of methylotrophic metabolism. In Methylobacterium extorquens DM4 of known genome sequence, dcmA lies on a 126 kb dcm genomic island not found so far in other DCM‐dechlorinating strains. An experimental search for the molecular determinants involved in specific cellular responses of strain DM4 growing with DCM was performed. Random mutagenesis with a minitransposon containing a promoterless reporter gfp gene yielded 25 dcm mutants with a specific DCM‐associated phenotype. Differential proteomic analysis of cultures grown with DCM and with methanol defined 38 differentially abundant proteins. The 5.5 kb dcm islet directly involved in DCM dehalogenation is the only one of seven gene clusters specific to the DCM response to be localized within the dcm genomic island. The DCM response was shown to involve mainly the core genome of Methylobacterium extorquens, providing new insights on DCM‐dependent adjustments of C1 metabolism and gene regulation, and suggesting a specific stress response of Methylobacterium during growth with DCM. Fatty acid, hopanoid and peptidoglycan metabolisms were affected, hinting at the membrane‐active effects of DCM due to its solvent properties. A chloride‐induced efflux transporter termed CliABC was also newly identified. Thus, DCM dechlorination driven by the dcm islet elicits a complex adaptive response encoded by the core genome common to dechlorinating as well as non‐dechlorinating Methylobacterium strains.
Structural, mass and elemental analyses of storage granules in methanogenic archaeal cells
Authors: Toso Daniel B. , Henstra Anne M. , Gunsalus Robert P. , Zhou Z. Hong 
Published: August 2011

SummaryStorage granules are an important component of metabolism in many organisms spanning the bacterial, eukaryal and archaeal domains, but systematic analysis of their organization inside cells is lacking. In this study, we identify and characterize granule‐like inclusion bodies in a methanogenic archaeon, Methanospirillum hungatei, an anaerobic microorganism that plays an important role in nutrient recycling in the ecosystem. Using cryo electron microscopy, we show that granules in mature M. hungatei are amorphous in structure with a uniform size. Energy dispersive X‐ray spectroscopy analysis establishes that each granule is a polyphosphate body (PPB) that consists of high concentrations of phosphorous and oxygen, and increased levels of iron and magnesium. By scanning transmission electron tomography, we further estimate that the mass density within a PPB is a little less than metal titanium at room temperature and is about four times higher than that of the surrounding cytoplasm. Finally, three‐dimensional cryo electron tomography reveals that PPBs are positioned off‐centre in their radial locations relative to the cylindrical axis of the cell, and almost uniformly placed near cell ends. This positioning ability points to a genetic program that spatially and temporally directs the accumulation of polyphosphate into a storage granule, perhaps for energy‐consuming activities, such as cell maintenance, division or motility.
Rivaroxaban for the prevention and treatment of venous thromboembolism
Authors: Turpie Alexander G.G. 
Published: August 2011

AbstractVenous thromboembolism (VTE) is a common and often life‐threatening cardiovascular disorder. Patients undergoing total hip replacement or total knee replacement surgery are at increased risk of VTE. In this setting, clinical practice guidelines recommend the use of low molecular weight heparins, vitamin K antagonists or fondaparinux for the prevention of VTE. However, the use of these anticoagulants is beset by practical difficulties that reduce compliance to therapy and adherence to recommended guidelines. New oral anticoagulants (OACs) that are administered in fixed doses without the need for monitoring are now being introduced to clinical practice. Rivaroxaban, dabigatran and apixaban are either approved or in advanced stages of clinical development for the prevention and/or treatment of VTE. This article provides an overview of the phase III clinical development programmes for these novel OACs, with special focus on rivaroxaban. With encouraging data already emerging, the promise of a simplified single‐drug approach for VTE treatment is on the horizon.
Response patterns to bronchodilator and quantitative computed tomography in chronic obstructive pulmonary disease
Authors: Lee Jae Seung , Huh Jin Won , Chae Eun Jin , Seo Joon Beom , Ra Seung Won , Lee Ji‐Hyun , Kim Eun‐Kyung , Lee Young Kyung , Kim Tae‐Hyung , Kim Woo Jin , Lee Jin Hwa , Lee Sang‐Min , Lee Sangyeub , Lim Seong Yong , Shin Tae Rim , Yoon Ho Il , Sheen Seung Soo , Oh Yeon‐Mok , Lee Sang‐Do 
Published: August 2011

SummaryBackground:  Patients with chronic obstructive pulmonary disease (COPD) show different spirometric response patterns to bronchodilator, such that some patients show improvement principally in expiratory flow (forced expiratory volume in 1 s; FEV1), whereas others respond by improvement of lung volume (forced vital capacity; FVC). The mechanisms of these different response patterns to bronchodilator remain unclear. We investigated the associations between bronchodilator responsiveness and quantitative computed tomography (CT) indices in patients with COPD.Methods:  Data on a total of 101 patients with stable COPD were retrospectively analysed. Volume and flow responses to bronchodilator were assessed by FVC and FEV1 changes before and after inhalation of salbutamol (400 μg). Volumetric CT was performed to quantify emphysema, air trapping and large airway thickness. Emphysema was assessed by the volume fraction of the lung under −950 Hounsfield units (HU; V950) at full inspiration and air trapping by the ratio of mean lung density (MLD) at full expiration and inspiration. Airway wall thickness and wall area percentage (WA%; defined as wall area/[wall area + lumen area] × 100), were measured near the origin of right apical and left apico‐posterior bronchus.Results:  Among quantitative CT indices, the CT emphysema index (V950 insp) showed a significant negative correlation with postbronchodilator FEV1 change (R = −0·213, P = 0·004), and the CT air‐trapping index correlated positively with postbronchodilator FVC change(R = 0·286, P≤0·001). Multiple linear regression analysis showed that CT emphysema index had independent association with postbronchodilator FEV1 change and CT air‐trapping index with postbronchodilator FVC change.Conclusion:  The degrees of emphysema and air trapping may contribute to the different response patterns to bronchodilator in patients with COPD.
Impact of technical assistants for venepuncture and intravenous cannulation on overall emergency department performance
Authors: Dinh Michael M , Green Timothy C , Newsome David , Bein Kendall J 
Published: August 2011

AbstractObjective: The objective of the article was to determine the effect of a technical assistant for venepuncture and i.v. cannulation on triage performance and patient length of stay in an ED.Methods: An observational study of daily ED performance was conducted at an inner city tertiary referral ED. Over a period of 158 consecutive days, data on triage performance and average length of stay were collected. A technical assistant was employed for 8–10 h per day to perform venepuncture, i.v. cannulation and electronic order entry. Study groups compared were days staffed by a technical assistant and days that were not staffed.Results: Days staffed by a technical assistant were associated with significantly higher triage performance for triage category three (mean 0.66, 95% CI 0.63–0.69 vs 0.58, 95% CI 0.54–0.62; P= 0.003) and lower average length of stay per patient for triage category two patients (mean length of stay 390 min, 95% CI 369–411 vs 425 min, 95% CI 399–451; P= 0.04). Triage performance thresholds for triage category three (75% of patients seen within 30 min) were met over twice as often on staffed days compared with control (39/96 [38%]vs 10/62 [16%], P= 0.004).Conclusion: Staffing the ED with a technical assistant was associated with improved ED performance for triage category three and average length of stay for triage category two patients.
Pain, analgesia and genetics
Authors: Muralidharan Arjun , Smith Maree T 
Published: August 2011

Abstract

Objectives
In the clinical setting, there is marked intersubject variability in the intensity of pain reported by patients with apparently similar pain states, as well as widely differing analgesic dosing requirements between individuals to produce satisfactory pain relief with tolerable side-effects. Genetic and environmental factors as well as their interaction are implicated, and these are discussed in this review.

Key findings
Pioneering work undertaken in mice more than a decade ago, showed a strong genetic contribution to levels of nociception/hypersensitivity as well as levels of antinociception produced by commonly available analgesic agents. To date more than 300 candidate ‘pain’ genes have been identified as potentially contributing to heritable differences in pain sensitivity and analgesic responsiveness in animals and humans, with this information available in a publicly accessible database http://www.jbldesign.com/jmogil/enter.html. Since then, many genetic association studies have been conducted in humans to investigate the possibility that single nucleotide polymorphisms (SNPs) in an individual gene may explain drug inefficacy or excessive toxicity experienced by a small subset of the whole population who have the rare allele for a particular SNP.

Summary
Despite the fact that SNPs in more than 20 genes that affect pain sensitivity or contribute to interindividual variability in responses to analgesic medications have been identified in the human genome, much of the data is conflicting. Apart from deficiencies in the design and conduct of human genetic association studies, recent research from other fields has implicated epigenetic mechanisms that facilitate dynamic gene-environment communication, as a possible explanation.
Azithromycin suppresses proliferation, interleukin production and mitogen-activated protein kinases in human peripheral-blood mononuclear cells stimulated with bacterial superantigen
Authors: Hiwatashi Yoko , Maeda Masaki , Fukushima Hisayo , Onda Kenji , Tanaka Sachiko , Utsumi Hiroya , Hirano Toshihiko 
Published: August 2011

Abstract

Objectives
Macrolide antibiotics are used for the treatment of immunological disorders such as psoriasis. However, few studies have investigated the immunoregulatory efficacy of macrolides in bacterial superantigen-stimulated immune cells.

Methods
The suppressive efficacies of azithromycin, clarithromycin, roxithromycin and prednisolone were evaluated in vitro against the concanavalin A- or toxic shock syndrome toxin 1 (TSST-1)-induced proliferation of peripheral-blood mononuclear cells (PBMCs) obtained from nine healthy subjects. The concentrations of six cytokines in a PBMC-culture medium were measured using bead-array procedures followed by flow cytometry. Cellular c-jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) activity were measured using cell-based ELISA procedures.

Key findings
Azithromycin, clarithromycin and roxithromycin inhibited the proliferation of both the concanavalin A- and superantigen-stimulated PBMCs dose-dependently. The effect of azithromycin was the strongest, with IC50 values of less than 5 µg/ml. Furthermore, the suppressive efficacy of prednisolone against concanavalin A- or TSST-1-stimulated PBMCs was significantly promoted in combination with 5 µg/ml azithromycin (P &lt; 0.002). The concentrations of TNF-α, interleukin (IL)-2, −4, −5 and −10 in the supernatant of concanavalin A- or TSST-1-stimulated PBMCs cultured for 72 h decreased by 65–98% in the presence of 5 µg/ml azithromycin. The stimulation of PBMCs with concanavalin A or TSST-1 increased cellular JNK and ERK activity, and 5 µg/ml azithromycin significantly attenuated the increased activity of JNK in the TSST-1-stimulated cells and ERK in the concanavalin A- and TSST-1-stimulated PBMCs, respectively (P &lt; 0.05).

Conclusions
Azithromycin suppresses mitogen- or superantigen-induced proliferation of PBMCs by possibly inhibiting both cellular JNK and ERK activity.
Myrtenal inhibits acetylcholinesterase, a known Alzheimer target
Authors: Kaufmann Dorothea , Dogra Anudeep Kaur , Wink Michael 
Published: August 2011

Abstract

Objectives
Inhibition of acetylcholinesterase (AChE) is a common treatment for early stages of the most general form of dementia, Alzheimer's disease. In this study selected components of essential oils, which carry a variety of important functional groups, were tested for their in-vitro anti-acetylcholinesterase activity.

Methods
In-vitro anti-acetylcholinesterase activity was measured by an adapted version of Ellman's colorimetric assay.

Key findings
1,8-cineole, carvacrol, myrtenal and verbenone apparently inhibited AChE; the highest inhibitory activity was observed for myrtenal (IC50 = 0.17 mm). This is the first study showing the AChE inhibitory activity of myrtenal.

Conclusions
Our investigations provided evidence for the efficacy of monoterpenes as inhibitors of AChE.
Single and Combination Herpes Simplex Virus Type 2 Glycoprotein Vaccines Adjuvanted with CpG Oligodeoxynucleotides or Monophosphoryl Lipid A Exhibit Differential Immunity That Is Not Correlated to Protection in Animal Models
Authors: Khodai Tansi , Chappell Debbie , Christy Clare , Cockle Paul , Eyles Jim , Hammond Daisy , Gore Katrina , McCluskie Michael J. , Evans Dana M. , Lang Susanne , Loudon Peter T. , Townend Tim , Wright Paul , West Kate , Bright Helen 
Published: August 2011

ABSTRACTDespite several attempts to develop an effective prophylactic vaccine for HSV-2, all have failed to show efficacy in the clinic. The most recent of these failures was the GlaxoSmithKline (GSK) subunit vaccine based on the glycoprotein gD with the adjuvant monophosphoryl lipid A (MPL). In a phase 3 clinical trial, this vaccine failed to protect from HSV-2 disease, even though good neutralizing antibody responses were elicited. We aimed to develop a superior, novel HSV-2 vaccine containing either gD or gB alone or in combination, together with the potent adjuvant CpG oligodeoxynucleotides (CPG). The immunogenic properties of these vaccines were compared in mice. We show that gB/CPG/alum elicited a neutralizing antibody response similar to that elicited by gD/CPG/alum vaccine but a significantly greater gamma interferon (IFN-γ) T cell response. Furthermore, the combined gB-gD/CPG/alum vaccine elicited significantly greater neutralizing antibody and T cell responses than gD/MPL/alum. The efficacies of these candidate vaccines were compared in the mouse and guinea pig disease models, including a novel male guinea pig genital disease model. These studies demonstrated that increased immune response did not correlate to improved protection. First, despite a lower IFN-γ T cell response, the gD/CPG/alum vaccine was more effective than gB/CPG/alum in mice. Furthermore, the gB-gD/CPG/alum vaccine was no more effective than gD/MPL/alum in mice or male guinea pigs. We conclude that difficulties in correlating immune responses to efficacy in animal models will act as a deterrent to researchers attempting to develop effective HSV vaccines.
Evaluation of the Recombinant 10-Kilodalton Immunodominant Region of the BP26 Protein of Brucella abortus for Specific Diagnosis of Bovine Brucellosis
Authors: Tiwari Arvind Kumar , Kumar Subodh , Pal Vijai , Bhardwaj Bhupendra , Rai Ganga Prasad 
Published: August 2011

ABSTRACTBrucellosis is a disease with worldwide distribution affecting animals and human beings.Brucella abortusis the causative agent of bovine brucellosis. The cross-reactions of currently available diagnostic procedures forB. abortusinfection result in false-positive reactions, which make the procedures unreliable. These tests are also unable to differentiateBrucella-infected and -vaccinated animals. The present work is focused on the use of a nonlipopolysaccharide (LPS) diagnostic antigen, a recombinant 10-kDa (r10-kDa) protein ofB. abortus, for specific diagnosis of brucellosis. The purified recombinant protein was used as a diagnostic antigen in plate enzyme-linked immunosorbent assay (p-ELISA) format to screen 408 bovine serum samples (70 presumptively negative, 308 random, and 30 vaccinated), and the results were compared with those of the Rose Bengal plate agglutination test (RBPT) and the standard tube agglutination test (STAT). Statistical analysis in presumptive negative samples revealed 100 and 98.41% specificity of p-ELISA with RBPT and STAT, and an agreement of 91.43% with the tests using Cohen's kappa statistics. In random samples, the agreement of p-ELISA was 77.92% and 80.52% with RBPT and STAT, respectively. p-ELISA investigation of vaccinated samples reported no false-positive results, whereas RBPT and STAT reported 30% and 96.6% false-positive results, respectively. The data suggest that p-ELISA with r10-kDa protein may be a useful method for diagnosis of bovine brucellosis. Furthermore, p-ELISA may also be used as a tool for differentiatingBrucella-vaccinated and naturally infected animals.
Refinement of a Human Challenge Model for Evaluation of Enterotoxigenic Escherichia coli Vaccines
Authors: Harro Clayton , Chakraborty Subhra , Feller Andrea , DeNearing Barbara , Cage Alicia , Ram Malathi , Lundgren Anna , Svennerholm Ann-Mari , Bourgeois August L. , Walker Richard I. , Sack David A. 
Published: August 2011

ABSTRACTEnterotoxigenicEscherichia coli(ETEC) strain H10407 (serotype O78:H11 producing heat-labile toxin [LT], heat-stable toxin [ST], and colonization factor I [CFA/I]) induces reliably high diarrheal attack rates (ARs) in a human challenge model at doses of ≥109CFU. A descending-dose challenge study was conducted with changes to the standard fasting time and buffer formulation, seeking conditions that permit lower inocula while maintaining reproducibly high ARs. In cohort 1, 20 subjects were fasted overnight and randomized 1:1:1:1 to receive H10407 at doses of 108CFU with bicarbonate, 108CFU with CeraVacx, 107CFU with bicarbonate, or 107CFU with CeraVacx. Subsequent cohorts received H10407 (107CFU with bicarbonate) with similar fasting conditions. Cohort 2 included 15 ETEC-naïve volunteers. Cohort 3 included 10 ETEC-naïve volunteers and 10 rechallenged volunteers. In all, 25/35 (71%) ETEC-naïve recipients of 107CFU of H10407 developed moderate or severe diarrhea (average maximum stool output/24 h = 1,042 g), and most (97%) shed H10407 (maximum geometric mean titer = 7.5 × 107CFU/gram of stool). Only one of 10 rechallenged volunteers developed diarrhea. These rechallenged subjects had reduced intestinal colonization, reflected by quantitative microbiology of fecal samples. Among the 35 ETEC-naïve subjects, anti-lipopolysaccharide (LPS) O78 serum antibody responses were striking, with positive IgA and IgG antibody responses in 33/35 (94%) and 25/35 (71%), respectively. Anti-heat-labile enterotoxin (LTB) serum IgA and IgG responses developed in 19/35 (54%) and 14/35 (40%) subjects, respectively. Anti-CFA/I serum IgA and IgG responses were detected in 15/35 (43%) and 8/35 (23%) subjects. After the second challenge, participants exhibited blunted anti-LPS and -LTB responses but a booster response to CFA/I. This ETEC model should prove useful in the future evaluation of ETEC vaccine candidates.
Chronic hepatitis in the English springer spaniel: clinical presentation, histological description and outcome
Authors: Bexfield N. H. , Andres‐Abdo C. , Scase T. J. , Constantino‐Casas F. , Watson P. J. 
Published: August 2011

Medical records and liver histology of 68 English springer spaniels (ESS) with a histological diagnosis of CH were reviewed retrospectively. PCR was performed on liver tissue for canine adenovirus‐1 (CAV‐1), canine parvovirus, canine herpesvirus and pathogenicLeptospiraspecies. Follow‐up information was obtained to calculate survival times. Median age at presentation was three years seven months (range, seven months to eight years five months) and there were 48 female and 20 male dogs. Clinical signs were non‐specific and five dogs were asymptomatic. All dogs had an increase in serum activity of one or more hepatobiliary enzymes. Histopathology demonstrated hepatocyte necrosis and apoptosis with varying amounts of fibrosis. A predominantly lymphoplasmacytic infiltrate throughout the hepatic parenchyma was found in all 68 dogs, but 45 of these dogs also had a neutrophilic component to the inflammatory infiltrate. There was no significant copper accumulation and no aetiological agent was identified by PCR. The median survival time was 189 days (range, 1 to 1211 days), 38 dogs died within three months and 12 dogs survived more than a year following diagnosis.
STABILITY BEHAVIOR AND DESIGN OF NONCONVENTIONAL COLD-FORMED STEEL STRUCTURES — RESEARCH REVIEW
Authors: DUNAI LÁSZLÓ , JAKAB GÁBOR 
Published: August 2011

In the paper, the methodology and main results of two research projects on nonconventional cold-formed thin-walled steel structures are presented. Laboratory tests, standard-based calculations, numerical models, and the connection of these to design method development are summarized. The implementation of the methodology is presented on two areas in detail: CompressionC-section members and a truss made of C-section members. The studied CompressionC-section members are of various cross-sectional arrangement and end- and lateral-supporting conditions. They consist of single or double asymmetric C-section members; in the latter case, either a back-to-back arrangement is applied or two sections are stuck in each other, forming a box-like closed section. The applied load is in each case compression with different eccentricities. Test arrangement, program, and results are presented; measured load-bearing capacities are compared to resistances calculated according to Eurocode 3, Part 1–3 where applicable, design rules for the cases not covered by the code are proposed. Trusses made of C-sections from the same product line are analyzed in the light of full-scale laboratory tests. EC3-based design formulae are derived for the failure modes obtained in the tests either by modifying existing application rules or by deriving new ones from these. Advanced numerical models of both structures are presented with focus on modeling imperfections, bolted connections, and joint rigidities.