bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diversity of Benzylsuccinate Synthase-Like (
bssA
) Genes in Hydrocarbon-Polluted Marine Sediments Suggests Substrate-Dependent Clustering
Authors: Acosta-Gonzï¿½lez Alejandro , Rossellï¿½-Mï¿½ra Ramon , Marquï¿½s Silvia 
Published: April 2013

ABSTRACT

The potential of hydrocarbon biodegradation in marine sediments was determined through the detection of a functional biomarker, the
bssA
gene, coding for benzylsuccinate synthase, the key enzyme of anaerobic toluene degradation. Eight
bssA
clone libraries (409 sequences) were constructed from polluted sediments affected by the
Prestige
oil spill in the Atlantic Islands National Park and from hydrocarbon-amended sediment microcosms in Mallorca. The amplified products and database-derived
bssA
-like sequences grouped into four major clusters, as determined by phylogenetic reconstruction, principal coordinate analysis (PCoA), and a subfamily prediction tool. In addition to the classical
bssA
sequences that were targeted, we were able to detect sequences homologous to the naphthylmethylsuccinate synthase gene (
nmsA
) and the alkylsuccinate synthase gene (
assA
), the
bssA
homologues for anaerobic 2-methylnaphthalene and alkane degradation, respectively. The detection of
bssA
-like variants was determined by the persistence and level of pollution in the marine samples. The observed level of gene diversity was lower in the Mallorca sediments, which were dominated by
assA
-like sequences. In contrast, the Atlantic Islands samples, which were highly contaminated with methylnaphthalene-rich crude oil, showed a high proportion of
nmsA
-like sequences. Some of the detected genes were phylogenetically related to
Deltaproteobacteria
communities, previously described as the predominant hydrocarbon degraders at these sites. Differences between all detected
bssA
-like genes described to date indicate separation between marine and terrestrial sequences and further subgrouping according to taxonomic affiliation. Global analysis suggested that
bssA
homologues appeared to cluster according to substrate specificity. We observed undetected divergent gene lineages of
bssA
homologues, which evidence the existence of new degrader groups in these environments.
Hybrid Cluster Proteins and Flavodiiron Proteins Afford Protection to Desulfovibrio vulgaris upon Macrophage Infection
Authors: Figueiredo Mafalda C. O. , Lobo Susana A. L. , Sousa Sara H. , Pereira Fábio P. , Wall Judy D. , Nobre Lígia S. , Saraiva Lígia M. 
Published: April 2013

ABSTRACT

Desulfovibrio
species are Gram-negative anaerobic sulfate-reducing bacteria that colonize the human gut. Recently,
Desulfovibrio
spp. have been implicated in gastrointestinal diseases and shown to stimulate the epithelial immune response, leading to increased production of inflammatory cytokines by macrophages. Activated macrophages are key cells of the immune system that impose nitrosative stress during phagocytosis. Hence, we have analyzed the
in vitro
and
in vivo
responses of
Desulfovibrio vulgaris
Hildenborough to nitric oxide (NO) and the role of the hybrid cluster proteins (HCP1 and HCP2) and rubredoxin oxygen oxidoreductases (ROO1 and ROO2) in NO protection. Among the four genes,
hcp2
was the gene most highly induced by NO, and the
hcp2
transposon mutant exhibited the lowest viability under conditions of NO stress. Studies in murine macrophages revealed that
D. vulgaris
survives incubation with these phagocytes and triggers NO production at levels similar to those stimulated by the cytokine gamma interferon (IFN-γ). Furthermore,
D. vulgaris
hcp
and
roo
mutants exhibited reduced viability when incubated with macrophages, revealing that these gene products contribute to the survival of
D. vulgaris
during macrophage infection.
DNA Substrate-Induced Activation of the Agrobacterium VirB/VirD4 Type IV Secretion System
Authors: Cascales Eric , Atmakuri Krishnamohan , Sarkar Mayukh K. , Christie Peter J. 
Published: April 2013

ABSTRACT

The bitopic membrane protein VirB10 of the
Agrobacterium
VirB/VirD4 type IV secretion system (T4SS) undergoes a structural transition in response to sensing of ATP binding or hydrolysis by the channel ATPases VirD4 and VirB11. This transition, detectable as a change in protease susceptibility, is required for DNA substrate passage through the translocation channel. Here, we present evidence that DNA substrate engagement with VirD4 and VirB11 also is required for activation of VirB10. Several DNA substrates (oncogenic T-DNA and plasmids RSF1010 and pCloDF13) induced the VirB10 conformational change, each by mechanisms requiring relaxase processing at cognate
oriT
sequences. VirD2 relaxase deleted of its translocation signal or any of the characterized relaxases produced in the absence of cognate DNA substrates did not induce the structural transition. Translocated effector proteins, e.g., VirE2, VirE3, and VirF, also did not induce the transition. By mutational analyses, we supplied evidence that the N-terminal periplasmic loop of VirD4, in addition to its catalytic site, is essential for early-stage DNA substrate transfer and the VirB10 conformational change. Further studies of VirB11 mutants established that three T4SS-mediated processes, DNA transfer, protein transfer, and pilus production, can be uncoupled and that the latter two processes proceed independently of the VirB10 conformational change. Our findings support a general model whereby DNA ligand binding with VirD4 and VirB11 stimulates ATP binding/hydrolysis, which in turn activates VirB10 through a structural transition. This transition confers an open-channel configuration enabling passage of the DNA substrate to the cell surface.
Nontypeable Haemophilus influenzae Carbonic Anhydrase Is Important for Environmental and Intracellular Survival
Authors: Langereis Jeroen D. , Zomer Aldert , Stunnenberg Hendrik G. , Burghout Peter , Hermans Peter W. M. 
Published: April 2013

ABSTRACT

Nontypeable
Haemophilus influenzae
(NTHi) is one of the leading causes of noninvasive mucosal infections, such as otitis media, sinusitis, and conjunctivitis. During its life cycle, NTHi is exposed to different CO
2
levels, which vary from ∼0.04% in ambient air during transmission to a new host to over 5% in the respiratory tract and tissues of the human host during colonization and disease. We used the next-generation sequencing Tn-seq technology to identify genes essential for NTHi adaptation to changes in environmental CO
2
levels. It appeared that
H. influenzae
carbonic anhydrase (HICA), which catalyzes the reversible hydration of CO
2
to bicarbonate, is a molecular factor that is conditionally essential for NTHi survival in ambient air. Growth of NTHi Δ
can
strains was restored under 5% CO
2
-enriched conditions, by supplementation of the growth medium with sodium bicarbonate, or by genetic complementation with the
can
gene. Finally, we showed that HICA not only is essential for environmental survival but also appeared to be important for intracellular survival in host cells. Hence, HICA is important for NTHi niche adaptation.
Identification and Assessment of Anderson-Fabry Disease by Cardiovascular Magnetic Resonance Noncontrast Myocardial T1 Mapping
Authors: Sado Daniel M. , White Steven K. , Piechnik Stefan K. , Banypersad Sanjay M. , Treibel Thomas , Captur Gabriella , Fontana Marianna , Maestrini Viviana , Flett Andrew S. , Robson Matthew D. , Lachmann Robin H. , Murphy Elaine , Mehta Atul , Hughes Derralynn , Neubauer Stefan , Elliott Perry M. , Moon James C. 
Published: April 2013

Background—
Anderson-Fabry disease (AFD) is a rare but underdiagnosed intracellular lipid disorder that can cause left ventricular hypertrophy (LVH). Lipid is known to shorten the magnetic resonance imaging parameter T1. We hypothesized that noncontrast T1 mapping by cardiovascular magnetic resonance would provide a novel and useful measure in this disease with potential to detect early cardiac involvement and distinguish AFD LVH from other causes.

Methods and Results—

Two hundred twenty-seven subjects were studied: patients with AFD (n=44; 55% with LVH), healthy volunteers (n=67; 0% with LVH), patients with hypertension (n=41; 24% with LVH), patients with hypertrophic cardiomyopathy (n=34; 100% with LVH), those with severe aortic stenosis (n=21; 81% with LVH), and patients with definite amyloid light-chain (AL) cardiac amyloidosis (n=20; 100% with LVH). T1 mapping was performed using the shortened modified Look-Locker inversion sequence on a 1.5-T magnet before gadolinium administration with primary results derived from the basal and midseptum. Compared with health volunteers, septal T1 was lower in AFD and higher in other diseases (AFD versus healthy volunteers versus other patients, 882±47, 968±32, 1018±74 milliseconds;
P
<0.0001). In patients with LVH (n=105), T1 discriminated completely between AFD and other diseases with no overlap. In AFD, T1 correlated inversely with wall thickness (
r
=−0.51;
P
=0.0004) and was abnormal in 40% of subjects who did not have LVH. Segmentally, AFD showed pseudonormalization or elevation of T1 in the left ventricular inferolateral wall, correlating with the presence or absence of late gadolinium enhancement (1001±82 versus 891±38 milliseconds;
P
<0.0001).

Conclusions—
Noncontrast T1 mapping shows potential as a unique and powerful measurement in the imaging assessment of LVH and AFD.
NADPH Oxidase 1 Plays a Key Role in Diabetes Mellitus–Accelerated Atherosclerosis
Authors: Gray Stephen P. , Di Marco Elyse , Okabe Jun , Szyndralewiez Cedric , Heitz Freddy , Montezano Augusto C. , de Haan Judy B. , Koulis Christine , El-Osta Assam , Andrews Karen L. , Chin-Dusting Jaye P. F. , Touyz Rhian M. , Wingler Kirstin , Cooper Mark E. , Schmidt Harald H. H. W. , Jandeleit-Dahm Karin A 
Published: April 2013

Background—
In diabetes mellitus, vascular complications such as atherosclerosis are a major cause of death. The key underlying pathomechanisms are unclear. However, hyperglycemic oxidative stress derived from NADPH oxidase (Nox), the only known dedicated enzyme to generate reactive oxygen species appears to play a role. Here we identify the Nox1 isoform as playing a key and pharmacologically targetable role in the accelerated development of diabetic atherosclerosis.

Methods and Results—
Human aortic endothelial cells exposed to hyperglycemic conditions showed increased expression of Nox1, oxidative stress, and proinflammatory markers in a Nox1-siRNA reversible manner. Similarly, the specific Nox inhibitor, GKT137831, prevented oxidative stress in response to hyperglycemia in human aortic endothelial cells. To examine these observations in vivo, we investigated the role of Nox1 on plaque development in apolipoprotein E–deficient mice 10 weeks after induction of diabetes mellitus. Deletion of Nox1, but not Nox4, had a profound antiatherosclerotic effect correlating with reduced reactive oxygen species formation, attenuation of chemokine expression, vascular adhesion of leukocytes, macrophage infiltration, and reduced expression of proinflammatory and profibrotic markers. Similarly, treatment of diabetic apolipoprotein E–deficient mice with GKT137831 attenuated atherosclerosis development.

Conclusions—
These studies identify a major pathological role for Nox1 and suggest that Nox1-dependent oxidative stress is a promising target for diabetic vasculopathies, including atherosclerosis.
Thucydides’ Take on the Corinthian Navy. οἵ τε γὰρ Κορίνθιοι ἡγήσαντο κρατεῖν εἰ µὴ καὶ πολὺ ἐκρατοῦντο, ‘The Corinthians believed they were victors if they were only just defeated’
Authors: McKenzie Nicholas J. , Hannah Patricia A. 
Published: April 2013

Abstract
This paper closely examines Thucydides’ presentation of three naval battles fought in the Corinthian Gulf and the battle of Sybota off north-west Greece, in order to show how his version of the action does not just stress the pervasive impression of Athenian dominance and downplay the Peloponnesian performance, but extends to characterising the Corinthian fleet in a surprisingly negative way. In the first battle he claims that they were ignorant of the local weather patterns, in the second of the underwater hazards, and after the third that ‘The Corinthians believed they were victors if they were only just defeated’. His account of the earlier battle off Corcyra is similarly flawed, since by focussing on the participants’ treaty obligations he fails to bring out the significance of the Corinthian naval victory for the history of Greek warfare. The reader of The Peloponnesian War is encouraged not to question Thucydides’ disparaging record of the Corinthian navy, as it reinforces his focus on a bipartite contest between Athens and Sparta. However, a case is made here for a more positive assessment of Corinthian involvement in the modified design of the trireme and the revision of naval tactics in the late fifth century BC.
Triptan nonresponders: Do they exist and who are they?
Authors: Viana Michele , Genazzani Armando A , Terrazzino Salvatore , Nappi Giuseppe , Goadsby Peter J 
Published: April 2013

Background: Triptans represent the best treatment option for most migraine attacks, although this is not as well studied as it might be in controlled trials. Their efficacy and tolerability vary, both between agents, and from patient to patient, with about 30%–40% of patients not responding adequately to therapy. As yet unexplained, the failure of one triptan does not predict failure with another, and therefore triptan nonresponders cannot be defined as individuals who have failed a single triptan. Five clinical studies provide evidence that switching from a triptan that is ineffective to a second one can result in effective treatment in a proportion of patients. Systematic studies investigating whether there are patients who do not respond to all triptans in all formulations are lacking. Methods: Here we discuss the importance of identifying triptan nonresponders, the literature supporting their existence, and the issues to be resolved to design trials to investigate this. Conclusion: So far, no scientific data about the presence of a triptan nonresponder population are available. We propose a pragmatic study design to assess the existence of this subpopulation, recognizing the complexity of the question and the likelihood that more than one issue is at play in nonresponders.
Ability of the new AT1 receptor blocker azilsartan to block angiotensin II-induced AT1 receptor activation after wash-out
Authors: Miura Shin-ichiro , Matsuo Yoshino , Nakayama Asuka , Tomita Sayo , Suematsu Yasunori , Saku Keijiro 
Published: April 2013

Introduction: The recently approved angiotensin II (Ang II) type 1 (AT1) receptor blocker (ARB) azilsartan strongly reduces blood pressure (BP) in patients with hypertension. We previously reported that azilsartan showed unique binding behavior to the AT1 receptor because of its 5-oxo-1,2,4-oxadiazole moiety. However, the ability of azilsartan to block Ang II-dependent AT1 receptor activation is not yet clear. Materials and methods: Azilsartan and a derivative of azilsartan (azilsartan-7H) that lacks a carboxyl group at the benzimidazole ring were used. Ang II-induced inositol phosphate (IP) production and extracellular signal-regulated kinase (ERK) activation were analyzed in a cell-based wash-out assay. Results: Azilsartan, but not azilsartan-7H, completely blocked Ang II-induced IP production and ERK activation. Our previous report demonstrated that azilsartan mainly interacts with Tyr113, Lys199, and Gln257 in the AT1 receptor. The interactions between azilsartan and Tyr113 and Gln257, but not Lys199, were critical for blocking Ang II-induced IP production and ERK activation after wash-out. Conclusions: Although our findings regarding the molecule-specific effects of azilsartan are based on basic research, they may lead to an exciting insight into the mechanism of azilsartan.
Prognostic impact and targeting of CRM1 in acute myeloid leukemia
Authors: Kojima Kensuke , Kornblau Steven M. , Ruvolo Vivian , Dilip Archana , Duvvuri Seshagiri , Davis R. Eric , Zhang Min , Wang Zhiqiang , Coombes Kevin R. , Zhang Nianxiang , Qiu Yi Hua , Burks Jared K. , Kantarjian Hagop , Shacham Sharon , Kauffman Michael , Andreeff Michael 
Published: April 2013

Key Points
High CRM1 expression was associated with short survival of AML patients. CRM1 inhibitor KPT-185 induces apoptosis mainly in a p53-dependent manner, whereas inhibition of proliferation was p53 independent.
CD41 expression marks myeloid-biased adult hematopoietic stem cells and increases with age
Authors: Gekas Christos , Graf Thomas 
Published: April 2013

Key PointsIntegrin CD41, thought to absent on adult HSCs, marks a novel subset of myeloid-biased long-term HSCs that becomes prevalent with age. Loss of CD41 leads to transplantable hematopoietic defects that affect HSC survival and maintenance and are, in part, mediated by platelet loss.
Automated quantification of radiological patterns predicts survival in idiopathic pulmonary fibrosis
Authors: Maldonado Fabien , Moua Teng , Rajagopalan Srinivasan , Karwoski Ronald A. , Raghunath Sushravya , Decker Paul A. , Hartman Thomas E. , Bartholmai Brian J. , Robb Richard A. , Ryu Jay H. 
Published: April 2013

Accurate assessment of prognosis in idiopathic pulmonary fibrosis remains elusive due to significant individual radiological and physiological variability. We hypothesised that short-term radiological changes may be predictive of survival.We explored the use of CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Rating), a novel software tool developed by the Biomedical Imaging Resource Laboratory at the Mayo Clinic Rochester (Rochester, MN, USA) for the analysis and quantification of parenchymal lung abnormalities on high-resolution computed tomography. We assessed baseline and follow-up (time-points 1 and 2, respectively) high-resolution computed tomography scans in 55 selected idiopathic pulmonary fibrosis patients and correlated CALIPER-quantified measurements with expert radiologists’ assessments and clinical outcomes.Findings of interval change (mean 289 days) in volume of reticular densities (hazard ratio 1.91, p=0.006), total volume of interstitial abnormalities (hazard ratio 1.70, p=0.003) and per cent total interstitial abnormalities (hazard ratio 1.52, p=0.017) as quantified by CALIPER were predictive of survival after a median follow-up of 2.4 years. Radiologist interpretation of short-term global interstitial lung disease progression, but not specific radiological features, was also predictive of mortality.These data demonstrate the feasibility of quantifying interval short-term changes on high-resolution computed tomography and their possible use as independent predictors of survival in idiopathic pulmonary fibrosis.
Rhinovirus infection and healthcare utilisation in prematurely born infants
Authors: Drysdale Simon B. , Alcazar-Paris Mireia , Wilson Theresa , Smith Melvyn , Zuckerman Mark , Broughton Simon , Rafferty Gerrard F. , Peacock Janet L. , Johnston Sebastian L. , Greenough Anne 
Published: April 2013

Our aim was to determine whether rhinovirus (RV) lower respiratory tract infections (LRTIs) in prematurely born infants increase health-related cost of care during infancy.153 infants born at <36 weeks of gestation were prospectively followed to 1 year. Cost of care was calculated from the National Health Service reference costing scheme and healthcare utilisation determined by examining hospital/general practitioner records.20 infants developed RV LRTIs (RV group), 17 respiratory syncytial virus (RSV) LRTIs (RSV group), 12 both RV and RSV LRTIs (RV/RSV group) and 74 had no LRTI (no LRTI group). Compared with the no LRTI group, the RV/RSV LRTI group had the greatest increase in adjusted mean cost (difference GBP 5769), followed by the RV LRTI group (difference GBP 278) and, finally, the RSV LRTI group (difference GBP 172) (p=0.045). The RV group had more outpatient (p<0.05) and respiratory-related general practitioner (p<0.05) attendances, more wheezed at follow-up (p<0.001) than the no LRTI group and more had respiratory-related outpatient attendances than the RSV LRTI group (p<0.05).We conclude that RV LRTIs were associated with increased health-related cost of care during infancy; our results suggest that the RV group compared with the RSV group suffered greater chronic respiratory morbidity.
Sex Differences in All-Cause and Cardiovascular Mortality, Hospitalization for Individuals With and Without Diabetes, and Patients With Diabetes Diagnosed Early and Late
Authors: Roche Madonna M. , Wang Peizhong Peter 
Published: April 2013

OBJECTIVE
To compare risk of all-cause mortality, cardiovascular disease (CVD) mortality, acute myocardial infarction (AMI) mortality, stroke mortality, and hospitalizations for males and females with and without diabetes and those with diabetes diagnosed early and late.

RESEARCH DESIGN AND METHODS
We conducted a population-based retrospective cohort study including 73,783 individuals aged 25 years or older in Newfoundland and Labrador, Canada (15,152 with diabetes; 9,517 with late diagnoses).

RESULTS
Males and females with diabetes had an increased risk of all-cause mortality, CVD mortality, AMI mortality, and CVD hospitalizations compared with individuals without diabetes, and the risk was stronger in females than in males. For females, risks of all-cause mortality (hazard ratio [HR] 1.85 [95% CI 1.74–1.96]) and CVD hospitalizations (2.57 [2.24–2.94]) were significantly higher compared with their male counterparts (1.59 [1.51–1.69] and 1.92 [1.72–2.14]). Females with diabetes diagnosed late had an increased risk of CVD mortality (6.54 [4.80–8.91]) and CVD hospitalizations (5.22 [4.31–6.33]) compared with females without diabetes, and both were significantly higher compared with their male counterparts (3.44 [2.47–4.79]) and (3.33 [2.80–3.95]).

CONCLUSIONS
Females with diabetes have a greater risk of mortality than males with diabetes. CVD has a greater impact on females with diabetes than males, especially when diagnosed at a later stage. Different management strategies should be considered for males and females and those with early and late diagnoses of diabetes.