bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ChrSA and HrrSA Two-Component Systems Are Required for Transcriptional Regulation of the
hemA
Promoter in Corynebacterium diphtheriae
Authors: Burgos Jonathan M. , Schmitt Michael P. 
Published: July 2016

ABSTRACT

Corynebacterium diphtheriae
utilizes heme and hemoglobin (Hb) as iron sources for growth in low-iron environments. In
C. diphtheriae
, the two-component signal transduction systems (TCSs) ChrSA and HrrSA are responsive to Hb levels and regulate the transcription of promoters for
hmuO
,
hrtAB
, and
hemA
. ChrSA and HrrSA activate transcription at the
hmuO
promoter and repress transcription at
hemA
in an Hb-dependent manner. In this study, we show that HrrSA is the predominant repressor at
hemA
and that its activity results in transcriptional repression in the presence and absence of Hb, whereas repression of
hemA
by ChrSA is primarily responsive to Hb. DNA binding studies showed that both ChrA and HrrA bind to the
hemA
promoter region at virtually identical sequences. ChrA binding was enhanced by phosphorylation, while binding to DNA by HrrA was independent of its phosphorylation state. ChrA and HrrA are phosphorylated
in vitro
by the sensor kinase ChrS, whereas no kinase activity was observed with HrrS
in vitro
. Phosphorylated ChrA was not observed
in vivo
, even in the presence of Hb, which is likely due to the instability of the phosphate moiety on ChrA. However, phosphorylation of HrrA was observed
in vivo
regardless of the presence of the Hb inducer, and genetic analysis indicates that ChrS is responsible for most of the phosphorylation of HrrA
in vivo
. Phosphorylation studies strongly suggest that HrrS functions primarily as a phosphatase and has only minimal kinase activity. These findings collectively show a complex mechanism of regulation at the
hemA
promoter, where both two-component systems act in concert to optimize expression of heme biosynthetic enzymes.

IMPORTANCE
Understanding the mechanism by which two-component signal transduction systems function to respond to environmental stimuli is critical to the study of bacterial pathogenesis. The current study expands on the previous analyses of the ChrSA and HrrSA TCSs in the human pathogen
C. diphtheriae
. The findings here underscore the complex interactions between the ChrSA and HrrSA systems in the regulation of the
hemA
promoter and demonstrate how the two systems complement one another to refine and control transcription in the presence and absence of Hb.
Mutations in the Plasmodium falciparum Cyclic Amine Resistance Locus (PfCARL) Confer Multidrug Resistance
Authors: LaMonte Gregory , Lim Michelle Yi-Xiu , Wree Melanie , Reimer Christin , Nachon Marie , Corey Victoria , Gedeck Peter , Plouffe David , Du Alan , Figueroa Nelissa , Yeung Bryan , Bifani Pablo , Winzeler Elizabeth A. 
Published: July 2016

ABSTRACT

Mutations in the
Plasmodium falciparum
cyclic amine resistance locus (PfCARL) are associated with parasite resistance to the imidazolopiperazines, a potent class of novel antimalarial compounds that display both prophylactic and transmission-blocking activity, in addition to activity against blood-stage parasites. Here, we show that
pfcarl
encodes a protein, with a predicted molecular weight of 153 kDa, that localizes to the
cis
-Golgi apparatus of the parasite in both asexual and sexual blood stages. Utilizing clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene introduction of 5 variants (L830V, S1076N/I, V1103L, and I1139K), we demonstrate that mutations in
pfcarl
are sufficient to generate resistance against the imidazolopiperazines in both asexual and sexual blood-stage parasites. We further determined that the mutant PfCARL protein confers resistance to several structurally unrelated compounds. These data suggest that PfCARL modulates the levels of small-molecule inhibitors that affect Golgi-related processes, such as protein sorting or membrane trafficking, and is therefore an important mechanism of resistance in malaria parasites.

IMPORTANCE
Several previous
in vitro
evolution studies have implicated the
Plasmodium falciparum
cyclic amine resistance locus (PfCARL) as a potential target of imidazolopiperazines, potent antimalarial compounds with broad activity against different parasite life cycle stages. Given that the imidazolopiperazines are currently being tested in clinical trials, understanding their mechanism of resistance and the cellular processes involved will allow more effective clinical usage.
After All, Only Millions?
Authors: Amann Rudolf , Rosselló-Móra Ramon 
Published: July 2016

ABSTRACT

An update on the census of species of
Archaea
and
Bacteria
published recently in mBio (P. D. Schloss, R. A. Girard, T. Martin, J. Edwards, and J. C. Thrash, mBio 7:e00201-16, 2016,
http://dx.doi.org/10.1128/mBio.00201-16
) showed again that, despite ever-increasing sequencing efforts, the PCR-based retrieval of 16S rRNA genes is approaching saturation. On average, 95% of the genes analyzed today are identical to those present in public databases, with rarefaction analysis indicating that about one-third of the bacterial and archaeal diversity has already been covered. Therefore, despite estimates of up to 10
12
microbial species, the option should be considered that the census of
Archaea
and
Bacteria
on planet Earth might yield only millions of species after all.
Effects of Electroacupuncture in a Mouse Model of Fibromyalgia: Role of N-Methyl-D-Aspartate Receptors and Related Mechanisms
Authors: Lu Kung-Wen , Hsieh Ching-Liang , Yang Jun , Lin Yi-Wen 
Published: July 2016

Objective N-methyl-D-aspartate receptor (NMDAR) activation and downstream transduction pathways are crucial for pain signalling. Fibromyalgia (FM) is a common pain syndrome of unclear aetiology that is often drug-refractory but may benefit from treatment with electroacupuncture (EA). We examined the contributions of NMDAR signalling to FM pain and EA responses in a mouse model. Methods A model of FM was established by acid saline injection in 32 mice and subgroups (n=8 each) were treated with EA (2 Hz, 15 min daily for 4 days) or minimal acupuncture (MA). Expression of NMDAR subunits, calmodulin-dependent protein kinase II (CaMKII), cyclic AMP response element binding protein (pCREB) and their corresponding phospho-activated forms were measured by Western blotting and immunohistochemistry. Results Acid saline injection induced significant mechanical hyperalgesia (paw withdrawal threshold 2.18±0.27 g, p<0.05 vs controls), which was reversed by EA (4.23±0.33 g, p<0.05 vs FM group) but not by MA (2.37±0.14 g, p<0.05 vs EA group). Expression levels of phosphorylated N-methyl-D-aspartate receptor (pNR)1 and pNR2B were significantly increased in the dorsal root ganglion of FM model mice (132.21±14.4% and 116.69±3.22% of control values), whereas NR1 and NR2B levels were unchanged (97.31±3.79% and 97.07%±2.27%, respectively). Expression levels of pCaMKIIα and pCREB were also higher in the FM group, and these changes were reversed by EA but not by MA. Similar changes in expression were observed in spinal cord neurons. Conclusions Reduced NMDAR−CaMKIIα−pCREB signalling is implicated in the positive effects of EA in FM. NMDAR signalling components may represent promising therapeutic targets for FM treatment.
HIV-1 infection and pregnancy in young women in Brazil: socioeconomic and drug resistance profiles in a cross-sectional study
Authors: Lima Yanna Andressa Ramos , Reis Mônica Nogueira Guarda , Cardoso Ludimila Paula Vaz , Stefani Mariane Martins Araújo 
Published: July 2016

ObjectivesTo describe socioeconomic and antiretroviral (ARV) drug resistance profiles among young pregnant women infected with HIV-1.SettingA public health antenatal programme responsible for screening ∼90 000 pregnant women per year for nine different infectious diseases in Central Western Brazil.Participants96 young pregnant women (15–24 years) infected with HIV-1.Primary and secondary outcome measuresStandard interviews and blood samples were taken at the time of recruitment, at the first medical appointment after confirmation of diagnosis of HIV-1 infection, and before ARV prophylaxis initiation. Clinical and laboratory data were retrieved from medical files. HIV-1polgene sequences (entire protease/PR, partial reverse transcriptase/RT) were obtained from plasma RNA. ARV resistance mutations (CPR/Stanford HIV-1; International AIDS Society-USA databases) were identified.ResultsThe median age was 21 years; most reported <8 years education; 73% were recently diagnosed. Approximately 20% (19/96) presented late for antenatal care (after 26 gestational weeks), while 49% reported ≥2 previous pregnancies. Possible heterosexual transmission by an HIV-1 infected partner (17%) and commercial sex work (2%) were reported. The median of CD4 cell count was 526 cells/mm3; the median viral load was: 10 056 copies/mL in ARV-naïve (48/96) patients and 5881 copies/mL in ARV-exposed (48/96) patients. Two probable seroconversion cases during pregnancy were identified in adolescents. One mother-to-child transmission case (1.0%) was observed. Transmitted drug resistance among ARV-naïve patients was 9.3% (CI 95% 3.3% to 19.6%); secondary drug resistance among ARV-exposed patients was 12.5% (CI 95% 4.7% to 25.6%).ConclusionsDespite high access to antenatal care, the low socioeconomic-educational profiles seen in these young HIV-1-infected women highlight the necessity of improved public health educational and preventive strategies regarding HIV infection and early unplanned pregnancy.
Interventions addressing risk factors of ischaemic heart disease in sub-Saharan Africa: a systematic review
Authors: Ebireri Jennifer , Aderemi Adewale V , Omoregbe Nicholas , Adeloye Davies 
Published: July 2016

BackgroundIschaemic heart disease (IHD) is currently ranked eighth among the leading causes of deaths in sub-Saharan Africa (sSA). Yet, effective population-wide preventive measures targeting risks in the region are still largely unavailable. We aimed to review population-wide and individual-level interventions addressing risk factors of IHD among adults in sSA.MethodsA systematic search of MEDLINE, EMBASE, Global Health and AJOL was conducted to identify studies focusing on population-wide and individual-level interventions targeting risks of IHD among adults in sSA. We conducted a detailed synthesis of basic findings of selected studies.ResultsA total of 2311 studies were identified, with only 9 studies meeting our selection criteria. 3 broad interventions were identified: dietary modifications, physical activity and community-based health promotion measures on tobacco and alcohol cessation. 3 studies reported significant reduction in blood pressure (BP), and another study reported statistically significant reduction in mean total cholesterol. Other outcome measures observed ranged from mild to no reduction in BP, blood glucose, body mass index and total cholesterol, respectively.ConclusionsWe cannot specify with all certainty contextually feasible interventions that can be effective in modifying IHD risk factors in population groups across sSA. We recommend more research on IHD, particularly on the understanding of the burden, geared towards developing and/or strengthening preventive and treatment interventions for the disease in sSA.
Endovascular thrombectomy for M2 occlusions: comparison between forced arterial suction thrombectomy and stent retriever thrombectomy
Authors: Kim Yong-Won , Son Seungnam , Kang Dong-Hun , Hwang Yang-Ha , Kim Yong-Sun 
Published: July 2016

BackgroundTo date there has been no direct comparison of two frequently used endovascular thrombectomy (EVT) methods (forced arterial suction thrombectomy (FAST) and stent retriever thrombectomy) in M2 occlusions. We review our experiences with EVT performed using FAST and stent retriever thrombectomy in such cases.MethodsThe subjects comprised 41 patients with an M2 occlusion who underwent EVT (25 with FAST, 16 with stent retriever thrombectomy). The patients' data were retrospectively analyzed to evaluate the technical characteristics and angiographic outcome of the two EVT techniques.ResultsThrombolysis In Cerebral Infarction (TICI) grades 2b–3 using the first chosen technique did not differ significantly between the two techniques (FAST 64.0% vs stent retriever thrombectomy 81.2%, p=0.305). Time from groin puncture to reperfusion was significantly shorter for stent retriever thrombectomy (53.0 vs 38.5 min; p=0.045). Distal embolization occurred in three cases (12.0%) in the FAST group and in four (26.7%) in the stent retriever group (p=0.362). However, the two techniques did not differ significantly in the final TICI 2b–3 rate (72.0% vs 87.5%; p=0.441). A frequent angiographic finding regarding the failure of FAST was that the M2 occlusion was located immediately after severe acute angulation between M1 and M2.ConclusionsStent retriever thrombectomy may provide faster reperfusion than FAST, while the FAST technique might be associated with lower distal embolization and a higher reperfusion rate for the first thrombectomy attempt, but without any significant difference in clinical outcome. When choosing the EVT method for M2 occlusions, consideration of the location of the occlusion and tortuosity between M1 and M2 might be helpful to achieve a better angiographic outcome.
Is intensive care monitoring necessary after coil embolization of unruptured intracranial aneurysms?
Authors: Stetler William R , Griauzde Julius , Saadeh Yamaan , Wilson Thomas J , Al-Holou Wajd N , Chaudhary Neeraj , Thompson B Gregory , Pandey Aditya S , Gemmete Joseph J 
Published: July 2016

IntroductionPatients with an unruptured intracranial aneurysm treated with coil embolization are routinely admitted to the intensive care unit (ICU) after the procedure; however, this practice is questionable. The purpose of this study was to determine if routine admission to the ICU is necessary for patients undergoing coil embolization of an unruptured intracranial aneurysm.MethodsWe conducted a retrospective cohort study of all patients undergoing elective endovascular treatment of an unruptured intracranial aneurysm between 2005 and 2012 at our institution. Multivariate regression analysis was performed to identify predictors of outcome. Cost savings analysis compared ICU admission to step-down or telemetry unit admission.Results311 unruptured intracranial aneurysms were treated by coil embolization (190), balloon remodeling (13), or stent-assisted coiling (108). Eleven (3.5%) neurologic complications were noted; 5 (1.6%) of these were permanent. Multivariate regression analysis identified female sex (p=0.028), hypercoagulability (p=0.021), aneurysm size >2 cm (p=0.003), and intraoperative rupture (p<0.001) as predictors of a post-procedural neurologic complication. Cost savings were 57% for admission to a step-down unit and 32% for admission to a telemetry unit compared with ICU admission.ConclusionsNeurologic complications are rare in the treatment of unruptured intracranial aneurysms, suggesting that routine ICU admission after treatment may not be necessary. Female sex, history of hypercoagulability, aneurysm size >2 cm, and an intraprocedural rupture were predictive of a postoperative complication. ICU monitoring in these subgroups may therefore be warranted.
The inner structure of dark matter haloes in the Hubble sequence
Authors: Del Popolo Antonino , Saburova Anna , Belvedere Gaetano 
Published: July 2016

We study how galaxy morphology changes the relation among the inner slope [Formula: see text] of galactic density profiles and the stellar mass, and rotation velocity. We find that the slope [Formula: see text] flattens monotonically from [Formula: see text] to [Formula: see text] going from giant galaxies (ellipticals, spirals) to dwarf galaxies ([Formula: see text]). At masses smaller than [Formula: see text], in the mass range dominated by nonrotational supported galaxies (e.g. dSphs), the slope steepens due to the offset in angular momentum of rotational dominated, and nonrotational dominated galaxies. A comparison with SPH simulations finds our result in qualitative agreement with them, but the inner slope [Formula: see text] at small stellar masses is flatter than that in their simulations. Density profiles become cuspy for [Formula: see text] in the range [Formula: see text]–[Formula: see text], similarly to Õnorbe.
Long-Term Persistence of Newly Initiated Warfarin Therapy in Chinese Patients With Nonvalvular Atrial Fibrillation
Authors: Wang Zhi-Zun , Du Xin , Wang Wei , Tang Ri-Bo , Luo Jing-Guang , Li Chao , Chang San-Shuai , Liu Xiao-Hui , Sang Cai-Hua , Yu Rong-Hui , Long De-Yong , Wu Jia-Hui , Bai Rong , Liu Nian , Ruan Yan-Fei , Dong Jian-Zeng , Ma Chang-Sheng 
Published: July 2016

Background—
Despite its therapeutic efficacy, warfarin is extremely underused in Chinese patients with nonvalvular atrial fibrillation (AF). Whether the nonpersistence of warfarin treatment contributes to its underuse is not known. The aims of this study were to determine nonpersistence rates of newly started warfarin treatment in Chinese patients with nonvalvular AF and to identify the factors associated with discontinuation of the treatment.

Methods and Results—

We identified 1461 patients with nonvalvular AF enrolled in the Chinese Atrial Fibrillation Registry (CAFR) who newly started on warfarin therapy in the period between August 1, 2011, and June 30, 2014. During a follow-up of 426±232 days, 22.1% of patients discontinued warfarin within 3 months, 44.4% within 1 year, and 57.6% within 2 years of initiation of therapy. Patients with no or partial insurance coverage had a higher likelihood to discontinue warfarin than those with full insurance coverage (adjusted hazard ratio 1.65, 95% confidence interval [1.03–2.64];
P
=0.038 and 1.66 [1.13–2.42];
P
=0.009, respectively). Paroxysmal AF (1.56 [1.28–1.92];
P
<0.0001), no prior stroke/transient ischemic attack/thromboembolism (1.60 [1.24–2.05];
P
=0.0003), and no dyslipidemia (1.34 [1.06–1.70];
P
=0.016) were also found to be independent predictors for nonpersistence of warfarin therapy.

Conclusions—
Nonpersistence of warfarin treatment becomes a serious problem for stroke prevention in Chinese patients with nonvalvular AF. Our findings can be used to identify patients who require closer attention or to develop better management strategy for oral anticoagulation therapy.
Congenital Heart Defects in the United States
Authors: Gilboa Suzanne M. , Devine Owen J. , Kucik James E. , Oster Matthew E. , Riehle-Colarusso Tiffany , Nembhard Wendy N. , Xu Ping , Correa Adolfo , Jenkins Kathy , Marelli Ariane J. 
Published: July 2016

Background:
Because of advancements in care, there has been a decline in mortality from congenital heart defects (CHDs) over the past several decades. However, there are no current empirical data documenting the number of people living with CHDs in the United States. Our aim was to estimate the CHD prevalence across all age groups in the United States in the year 2010.

Methods:
The age-, sex-, and severity-specific observed prevalence of CHDs in Québec, Canada, in the year 2010 was assumed to equal the CHD prevalence in the non-Hispanic white population in the United States in 2010. A race-ethnicity adjustment factor, reflecting differential survival between racial-ethnic groups through 5 years of age for individuals with a CHD and that in the general US population, was applied to the estimated non-Hispanic white rates to derive CHD prevalence estimates among US non-Hispanic blacks and Hispanics. Confidence intervals for the estimated CHD prevalence rates and case counts were derived from a combination of Taylor series approximations and Monte Carlo simulation.

Results:
We estimated that ≈2.4 million people (1.4 million adults, 1 million children) were living with CHDs in the United States in 2010. Nearly 300 000 of these individuals had severe CHDs.

Conclusions:
Our estimates highlight the need for 2 important efforts: planning for health services delivery to meet the needs of the growing population of adults with CHD and the development of surveillance data across the life span to provide empirical estimates of the prevalence of CHD across all age groups in the United States.
Hemoglobin Concentration and Risk of Incident Stroke in Community-Living Adults
Authors: Panwar Bhupesh , Judd Suzanne E. , Warnock David G. , McClellan William M. , Booth John N. , Muntner Paul , Gutiérrez Orlando M. 
Published: July 2016

Background and Purpose—
In previous observational studies, hemoglobin concentrations have been associated with an increased risk of stroke. However, these studies were limited by a relatively low number of stroke events, making it difficult to determine whether the association of hemoglobin and stroke differed by demographic or clinical factors.

Methods—
Using Cox proportional hazards analysis and Kaplan–Meier plots, we examined the association of baseline hemoglobin concentrations with incident stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a cohort of black and white adults aged ≥45 years.

Results—

A total of 518 participants developed stroke over a mean 7±2 years of follow-up. There was a statistically significant interaction between hemoglobin and sex (
P
=0.05) on the risk of incident stroke. In Cox regression models adjusted for demographic and clinical variables, there was no association of baseline hemoglobin concentration with incident stroke in men, whereas in women, the lowest (<12.4 g/dL) and highest (>14.0 g/dL) quartiles of hemoglobin were associated with higher risk of stroke when compared with the second quartile (12.4–13.2 g/dL; quartile 1: hazard ratio, 1.59; 95% confidence interval, 1.09–2.31; quartile 2: referent; quartile 3: hazard ratio, 0.91; 95% confidence interval, 0.59–1.38; quartile 4: hazard ratio, 1.59; 95% confidence interval, 1.08–2.35). Similar results were observed in models stratified by hemoglobin and sex and when hemoglobin was modeled as a continuous variable using restricted quadratic spline regression.

Conclusions—
Lower and higher hemoglobin concentrations were associated with a higher risk of incident stroke in women. No such associations were found in men.
Meteosat-Based Characterization of the Spatiotemporal Evolution of Warm Convective Cloud Fields over Central Europe
Authors: Bley Sebastian , Deneke Hartwig , Senf Fabian 
Published: July 2016

AbstractThe spatiotemporal evolution of warm convective cloud fields over central Europe is investigated on the basis of 30 cases using observations from the Spinning Enhanced Visible and Infrared Imager (SEVIRI) on board the geostationary Meteosat platforms. Cloud fields are tracked in successive satellite images using cloud motion vectors. The time-lagged autocorrelation is calculated for spectral reflectance and cloud property fields using boxes of 16 × 16 pixels and adopting both Lagrangian and Eulerian perspectives. The 0.6-μm reflectance, cloud optical depth, and water path show a similar characteristic Lagrangian decorrelation time of about 30 min. In contrast, significantly lower decorrelation times are observed for the cloud effective radius and droplet density. It is shown that the Eulerian decorrelation time can be decomposed into an advective component and a convective component using the spatial autocorrelation function. In an Eulerian frame cloud fields generally decorrelate faster than in a Lagrangian one. The Eulerian decorrelation time contains contributions from the spatial decorrelation of the cloud field advected by the horizontal wind. A typical spatial decorrelation length of 7 km is observed, which suggests that sampling of SEVIRI observations is better in the temporal domain than in the spatial domain when investigating small-scale convective clouds. An along-track time series of box-averaged cloud liquid water path is derived and compared with the time series that would be measured at a fixed location. Supported by previous results, it is argued that this makes it possible to discriminate between local changes such as condensation and evaporation on the one hand and advective changes on the other hand.