bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tc52 Amino-Terminal-Domain DNA Carried by Attenuated Salmonella enterica Serovar Typhimurium Induces Protection against a Trypanosoma cruzi Lethal Challenge
Authors: Matos Marina N. , Cazorla Silvia I. , Bivona Augusto E. , Morales Celina , Guzmán Carlos A. , Malchiodi Emilio L. 
Published: July 2014

ABSTRACT

In this work we immunized mice with DNA encoding full-length Tc52 or its amino- or carboxy-terminal (N- and C-term, respectively) domain carried by attenuated
Salmonella
as a DNA delivery system. As expected,
Salmonella
-mediated DNA delivery resulted in low antibody titers and a predominantly Th1 response, as shown by the ratio of IgG2a/IgG1-specific antibodies. Despite modest expression of Tc52 in trypomastigotes, the antibodies elicited by vaccination were able to mediate lysis of the trypomastigotes in the presence of complement and inhibit their invasion of mammal cells
in vitro
. The strongest functional activity was observed with sera from mice immunized with
Salmonella
carrying the N-term domain (SN-term), followed by Tc52 (STc52), and the C-term domain (SC-term). All immunized groups developed strong cellular responses, with predominant activation of Th1 cells. However, mice immunized with SN-term showed higher levels of interleukin-10 (IL-10), counterbalancing the inflammatory reaction, and also strong activation of Tc52-specific gamma interferon-positive (IFN-γ
+
) CD8
+
T cells. In agreement with this, although all prototypes conferred protection against infection, immunization with SN-term promoted greater protection than that with SC-term for all parameters tested and slightly better protection than that with STc52, especially in the acute stage of infection. We conclude that the N-terminal domain of Tc52 is the section of the protein that confers maximal protection against infection and propose it as a promising candidate for vaccine development.
NifA- and CooA-Coordinated
cowN
Expression Sustains Nitrogen Fixation by Rhodobacter capsulatus in the Presence of Carbon Monoxide
Authors: Hoffmann Marie-Christine , Pfänder Yvonne , Fehringer Maria , Narberhaus Franz , Masepohl Bernd 
Published: July 2014

ABSTRACT

Rhodobacter capsulatus
fixes atmospheric dinitrogen via two nitrogenases, Mo- and Fe-nitrogenase, which operate under different conditions. Here, we describe the functions in nitrogen fixation and regulation of the
rcc00574
(
cooA
) and
rcc00575
(
cowN
) genes, which are located upstream of the structural genes of Mo-nitrogenase,
nifHDK
. Disruption of
cooA
or
cowN
specifically impaired Mo-nitrogenase-dependent growth at carbon monoxide (CO) concentrations still tolerated by the wild type. The
cooA
gene was shown to belong to the Mo-nitrogenase regulon, which is exclusively expressed when ammonium is limiting. Its expression was activated by NifA1 and NifA2, the transcriptional activators of
nifHDK
. AnfA, the transcriptional activator of Fe-nitrogenase genes, repressed
cooA
, thereby counteracting NifA activation. CooA activated
cowN
expression in response to increasing CO concentrations. Base substitutions in the presumed CooA binding site located upstream of the
cowN
transcription start site abolished
cowN
expression, indicating that
cowN
regulation by CooA is direct. In conclusion, a transcription factor-based network controls
cowN
expression to protect Mo-nitrogenase (but not Fe-nitrogenase) under appropriate conditions.
RPA Inhibition Increases Replication Stress and Suppresses Tumor Growth
Authors: Glanzer Jason G. , Liu Shengqin , Wang Ling , Mosel Adam , Peng Aimin , Oakley Greg G. 
Published: July 2014

Abstract
The ATR/Chk1 pathway is a critical surveillance network that maintains genomic integrity during DNA replication by stabilizing the replication forks during normal replication to avoid replication stress. One of the many differences between normal cells and cancer cells is the amount of replication stress that occurs during replication. Cancer cells with activated oncogenes generate increased levels of replication stress. This creates an increased dependency on the ATR/Chk1 pathway in cancer cells and opens up an opportunity to preferentially kill cancer cells by inhibiting this pathway. In support of this idea, we have identified a small molecule termed HAMNO ((1Z)-1-[(2-hydroxyanilino)methylidene]naphthalen-2-one), a novel protein interaction inhibitor of replication protein A (RPA), a protein involved in the ATR/Chk1 pathway. HAMNO selectively binds the N-terminal domain of RPA70, effectively inhibiting critical RPA protein interactions that rely on this domain. HAMNO inhibits both ATR autophosphorylation and phosphorylation of RPA32 Ser33 by ATR. By itself, HAMNO treatment creates DNA replication stress in cancer cells that are already experiencing replication stress, but not in normal cells, and it acts synergistically with etoposide to kill cancer cells in vitro and slow tumor growth in vivo. Thus, HAMNO illustrates how RPA inhibitors represent candidate therapeutics for cancer treatment, providing disease selectivity in cancer cells by targeting their differential response to replication stress. Cancer Res; 74(18); 5165–72. ©2014 AACR.
TALEN-Mediated Somatic Mutagenesis in Murine Models of Cancer
Authors: Zhang Shuyuan , Li Lin , Kendrick Sara L. , Gerard Robert D. , Zhu Hao 
Published: July 2014

Abstract
Cancer genome sequencing has identified numerous somatic mutations whose biologic relevance is uncertain. In this study, we used genome-editing tools to create and analyze targeted somatic mutations in murine models of liver cancer. Transcription activator-like effector nucleases (TALEN) were designed against β-catenin (Ctnnb1) and adenomatous polyposis coli (Apc), two commonly mutated genes in hepatocellular carcinoma (HCC), to generate isogenic HCC cell lines. Both mutant cell lines exhibited evidence of Wnt pathway dysregulation. We asked whether these TALENs could create targeted somatic mutations after hydrodynamic transfection into mouse liver. TALENs targeting β-catenin promoted endogenous HCC carrying the intended gain-of-function mutations. However, TALENs targeting Apc were not as efficient in inducing in vivo homozygous loss-of-function mutations. We hypothesized that hepatocyte polyploidy might be protective against TALEN-induced loss of heterozygosity, and indeed Apc gene editing was less efficient in tetraploid than in diploid hepatocytes. To increase efficiency, we administered adenoviral Apc TALENs and found that we could achieve a higher mutagenesis rate in vivo. Our results demonstrate that genome-editing tools can enable the in vivo study of cancer genes and faithfully recapitulate the mosaic nature of mutagenesis in mouse cancer models. Cancer Res; 74(18); 5311–21. ©2014 AACR.
Non‐ST‐Elevation Myocardial Infarction in the United States: Contemporary Trends in Incidence, Utilization of the Early Invasive Strategy, and In‐Hospital Outcomes
Authors: Khera Sahil , Kolte Dhaval , Aronow Wilbert S. , Palaniswamy Chandrasekar , Subramanian Kathir Selvan , Hashim Taimoor , Mujib Marjan , Jain Diwakar , Paudel Rajiv , Ahmed Ali , Frishman William H. , Bhatt Deepak L. , Panza Julio A. , Fonarow Gregg C. 
Published: July 2014

Background

There has been a paradigm shift in the definition of timing of early invasive strategy (
EIS
) for patients admitted with non‐
ST
‐elevation myocardial infarction (
NSTEMI)
in the last decade. Data on trends of
EIS
for
NSTEMI
and associated in‐hospital outcomes are limited. Our aim is to analyze temporal trends in the incidence, utilization of early invasive strategy, and in‐hospital outcomes of
NSTEMI
in the United States.

Methods and Results

We analyzed the 2002–2011 Nationwide Inpatient Sample databases to identify all patients ≥40 years of age with the principal diagnosis of acute myocardial infarction (
AMI
) and
NSTEMI
. Logistic regression was used for overall, age‐, sex‐, and race/ethnicity‐stratified trend analysis. From 2002 to 2011, we identified 6 512 372 patients with
AMI
. Of these, 3 981 119 (61.1%) had
NSTEMI
. The proportion of patients with
NSTEMI
increased from 52.8% in 2002 to 68.6% in 2011 (adjusted odds ratio [
OR;
per year], 1.055; 95% confidence interval [
CI],
1.054 to 1.056) in the overall cohort. Similar trends were observed in age‐, sex‐, and race/ethnicity‐stratified groups. From 2002 to 2011, utilization of
EIS
at day 0 increased from 14.9% to 21.8% (
P
trend
<0.001) and utilization of
EIS
at day 0 or 1 increased from 27.8% to 41.4% (
P
trend
<0.001). Risk‐adjusted in‐hospital mortality in the overall cohort decreased during the study period (adjusted
OR
[per year], 0.976; 95%
CI,
0.974 to 0.978).

Conclusions

There have been temporal increases in the proportion of
NSTEMI
and, consistent with guidelines, greater utilization of
EIS
. This has been accompanied by temporal decreases in in‐hospital mortality and length of stay.
Ensemble Transform with 3D Rescaling Initialization Method
Authors: Ma Juhui , Zhu Yuejian , Hou Dingchen , Zhou Xiaqiong , Peña Malaquias 
Published: July 2014

Abstract
The ensemble transform with rescaling (ETR) method has been used to produce fast-growing components of analysis error in the NCEP Global Ensemble Forecast System (GEFS). The rescaling mask contained in the ETR method constrains the amplitude of perturbations to reflect regional variations of analysis error. However, because of a lack of suitable three-dimensional (3D) analysis error estimation, in the operational GEFS the mask is based on the estimated analysis error at 500 hPa and is not flow dependent but changes monthly. With the availability of an ensemble-based data assimilation system at NCEP, a 3D mask can be computed. This study generates initial perturbations by the ensemble transform with 3D rescaling (ET_3DR) and compares the performance with the ETR. Meanwhile, the ET_3DR is also applied within the ensemble Kalman filter (EnKF) method (hereafter EnKF_3DR).
Results from a set of experiments indicate that the 3D mask suppresses perturbations less in unstable regions. Relative to the ETR, the large amplitudes of the ET_3DR initial perturbations at 500 hPa better reflect areas of baroclinic instability over the extratropics and deep convection over the tropics. Furthermore, the maxima of the vertical distribution for the ET_3DR initial perturbations correspond to the heights of the subtropical westerly and tropical easterly jet regions. Such perturbations produce faster spread growths. Results with EnKF_3DR also show benefits from an orthonormalization by the ensemble transform algorithm and amplitude constraint by the 3D mask rescaling. Thus, the EnKF_3DR forecasts outperform the EnKF.
‘Ego-dystonicity’ in homosexuality: An Indian perspective
Authors: Sebastian Maroky Ami , Ratheesh Aswin , Viswanath Biju , Math Suresh Bada , Chandrashekar Channapatna R , Seshadri Shekhar P 
Published: July 2014

Background: Homosexual persons are targets of verbal and physical abuse, discrimination and face legal disadvantages in many countries, including India. These external factors could play a role in determining discomfort with their sexuality. Aims: We ascertained the association between ego-dystonicity of sexual orientation and indices of perceived acceptance, stigma and awareness of possible normative lifestyles. Methods: Fifty-one self-identified adult homosexual men were assessed using online questionnaires that covered information including their socio-demographic details; a Visual Analog Scale (VAS) that measured their degree of discomfort with their sexuality; Reactions to Homosexuality Scale, Perceived Acceptance Scale, Modified China Men Who Have Sex with Men (MSM) Stigma scale; and trait version of the Positive and Negative Affect Scale. The participants were also asked to provide a written narrative of their experiences which influenced their comfort with their sexuality. Results: Discomfort with sexuality significantly correlated with education, acceptance by friends and family, legal disadvantages, awareness and accessibility to non-heteronormative lifestyles and support systems and trait affect. Only acceptance by friends and awareness showed significance on linear regression. Qualitative analyses revealed external attributions for discomfort. Conclusions: Modifying external factors, reducing legal restrictions and improving societal acceptance and support systems could reduce ‘ego-dystonicity’. ‘Ego-dystonicity’ as a determinant for psychiatric classification and intervention needs to be reexamined.
Astragalin inhibits airway eotaxin-1 induction and epithelial apoptosis through modulating oxidative stress-responsive MAPK signaling
Authors: Cho In-Hee , Gong Ju-Hyun , Kang Min-Kyung , Lee Eun-Jung , Park Jung Han Yoon , Park Sang-Jae , Kang Young-Hee 
Published: July 2014

Abstract

Background
Eotaxin proteins are a potential therapeutic target in treating the peribronchial eosinophilia associated with allergic airway diseases. Since inflammation is often associated with an increased generation of reactive oxygen species (ROS), oxidative stress is a mechanistically imperative factor in asthma. Astragalin (kaempferol-3-O-glucoside) is a flavonoid with anti-inflammatory activity and newly found in persimmon leaves and green tea seeds. This study elucidated that astragalin inhibited endotoxin-induced oxidative stress leading to eosinophilia and epithelial apoptosis in airways.

Methods
Airway epithelial BEAS-2B cells were exposed to lipopolysaccharide (LPS) in the absence and presence of 1–20 μM astragalin. Western blot and immunocytochemical analyses were conducted to determine induction of target proteins. Cell and nuclear staining was also performed for ROS production and epithelial apoptosis.

Results
When airway epithelial cells were exposed to 2 μg/ml LPS, astragalin nontoxic at ≤20 μM suppressed cellular induction of Toll-like receptor 4 (TLR4) and ROS production enhanced by LPS. Both LPS and H2O2 induced epithelial eotaxin-1 expression, which was blocked by astragalin. LPS activated and induced PLCγ1, PKCβ2, and NADPH oxidase subunits of p22phox and p47phox in epithelial cells and such activation and induction were demoted by astragalin or TLR4 inhibition antagonizing eotaxin-1 induction. H2O2-upregulated phosphorylation of JNK and p38 MAPK was dampened by adding astragalin to epithelial cells, while this compound enhanced epithelial activation of Akt and ERK. H2O2 and LPS promoted epithelial apoptosis concomitant with nuclear condensation or caspase-3 activation, which was blunted by astragalin.

Conclusions
Astragalin ameliorated oxidative stress-associated epithelial eosinophilia and apoptosis through disturbing TLR4-PKCβ2-NADPH oxidase-responsive signaling. Therefore, astragalin may be a potent agent antagonizing endotoxin-induced oxidative stress leading to airway dysfunction and inflammation.
Assessment of the effect of Schistosoma haematobium co infection on malaria parasites and immune responses in rural populations in Gabon: study protocol
Authors: Ateba Ngoa Ulysse , Zinsou Jeannot Fréjus , Kassa Roland Fabrice Kassa , Ngoune Feugap Eliane , Honkpehedji Yabo Josiane , Massinga-Loembe Marguerite , Kenguele Moundounga Hilaire , Nkoma Mouima Anne Marie , Mbenkep Lima Honorine , Wammes Linda Judith , Mbow Moustapha , Kruize Yvonne , Mombo-Ngoma Ghyslain , Bouyoukou Hounkpatin Aurore Larissa , Dejon Agobe Jean Claude , Saadou Issifou , Lell Bertrand , Smits Hermelijn , Kremsner Peter Gottfried , Yazdanbakhsh Maria , Adegnika Ayola Akim 
Published: July 2014

Abstract

Background
Malaria and helminth co infection are common in tropical and subtropical areas where they affect the life of millions of people. While both helminth and malaria parasites have immunomodulatory activities, little is known about the consequence of co-infections on malaria antigen specific immune responses.

Method/Design
This study will be conducted in two rural areas of the Moyen Ogooué province in Gabon, endemic for both Plasmodium falciparum and Schistosoma haematobium infections. Participants, 5 to 50 years old, will be enrolled and grouped according to their infection status. S. haematobium and malaria parasites will be detected, demographic and clinical data will be recorded and blood will be collected for hematological as well as for immunological assays. The level of antibody specific to Plasmodium falciparum blood stage and gametocyte antigens will be measured using ELISA. PBMC will be isolated for phenotyping of different T cell subsets ex vivo by flow cytometry and for culture and cytokine response assessment.

Discussion
We will provide a comprehensive picture of the interaction between schistosomes and malaria parasites which co-localize in peripheral blood. We will test the hypothesis that schistosome infection has an impact on specific humoral as well as on cellular immune responses to malaria antigens.
Lipid rafts couple class A scavenger receptors to phospholipase A2 activation during macrophage adhesion
Authors: Vadali Shanthi , Post Steven R 
Published: July 2014

ABSTRACTSR-A mediated macrophage adhesion to modified ECM proteins in a process that involves physical attachment of SR-A to modified ECM and activation of Lyn-PI3K and PLA2-12/15-lipoxygenase signaling pathways. Structurally, SR-A-mediated cell adhesion requires a 6-aa membrane-proximal cytoplasmic motif. However, the mechanism that couples SR-A-mediated adhesion to activation of these distinct signaling pathways is not known. For other adhesion receptors, including integrins, localization in cholesterol-rich LRs is an important mechanism for coupling the receptor with the activation of specific signaling pathways. We hypothesized that SR-A-mediated macrophage adhesion might also involve LRs. Our results demonstrate that SR-A is enriched in LRs in HEK cells that heterologously express SR-A and in macrophages that endogenously expressed the receptor. We further show that a truncated SR-A construct (SR-AΔ1–49), which mediates cell adhesion but not ligand internalization, is also enriched in LRs, suggesting an association between LRs and SR-A-dependent cell adhesion. To examine this association more directly, we used the cholesterol chelator MβCD to deplete cholesterol and disrupt LR function. We found that cholesterol depletion significantly decreased SR-A-mediated macrophage adhesion. We further show that decreased SR-A-dependent macrophage adhesion following cholesterol depletion results from the inhibition of PLA2 but not PI3K activation. Overall, our results demonstrate an important role for LRs in selectively coupling SR-A with PLA2 activation during macrophage adhesion.
Microresistivity borehole image inpainting
Authors: Assous Said , Elkington Peter , Whetton James 
Published: July 2014

Images rendered from measurements made by wireline microresistivity imaging tools include longitudinal gaps whenever the well circumference exceeds the total width of the pad-mounted electrode arrays. The fraction of an image containing null data depends on tool design, and it is commonly approximately 30% for 261 mm (8.5 in.)-bit size wells increasing to approximately 50% in 311 mm (12.25 in.) wells. We use cues from the measured parts to infer information missing from the gaps; a method has been developed that simulates the process by decomposing the measured parts into their morphological components using sparse representations of multiscale multiorientation transforms, then recomposing the full-bore image assuming it to be efficiently represented by the transform’s elemental bases. The approach was evaluated using real data sets with a variety of geologic features, including full-coverage images from small diameter wells artificially obscured to simulate images from larger diameter wells. For borehole images dominated by curvilinear features, reconstructions from artificially obscured images were visually indistinguishable from the original unobscured images for a broad range of coverage loss and for all apparent dip angles below near-vertical, regardless of degree of parallelism (or lack thereof). Successful reconstruction of near-vertical features (including those with complex boundaries such as breakouts) was more dependent on coverage loss, but in these cases, the results were consistent with judgments made by interpreters. Therefore, we found that inpainting provides a consistent starting point for reproducible quantitative geologic analysis, and it is an enabler for automated feature recognition.
Pemetrexed and Cisplatin for the Treatment of Advanced, Persistent, or Recurrent Carcinoma of the Cervix: A Limited Access Phase II Trial of the Gynecologic Oncology Group
Authors: Miller David Scott , Blessing John A. , Ramondetta Lois M. , Pham Huyen Q. , Tewari Krishnansu S. , Landrum Lisa M. , Brown Jubilee , Mannel Robert S. 
Published: July 2014

Purpose To estimate the antitumor activity of pemetrexed and cisplatin with objective tumor response (partial and complete) in patients with advanced, persistent, or recurrent carcinoma of the cervix and to determine the nature and degree of toxicity of this regimen. Secondarily, this study will determine the effects of this regimen on progression-free survival and overall survival. Patients and Methods Eligible, consenting patients received pemetrexed 500 mg/m2 and cisplatin 50 mg/m2 intravenously repeated every 21 days until disease progression or adverse events prohibited further therapy. Patients received no prior therapeutic chemotherapy, except when administered concurrently with primary radiation therapy. Subsequent doses were adjusted according to observed toxicity and protocol guidelines. Adverse events were assessed with Common Terminology Criteria for Adverse Events v 3.0. The primary measure of efficacy was tumor response according to Response Evaluation Criteria in Solid Tumors. The study was stratified by prior radiation therapy. Results From September 2008 to November 2011, 55 patients were enrolled by five Gynecologic Oncology Group member institutions; of those, 54 patients were eligible and assessable. The regimen was well tolerated with 26% receiving more than nine cycles. The most common greater than grade 2 toxicities were neutropenia 35%, leukopenia 28%, and metabolic 28%. The overall response rate was 31% (one complete and 16 partial). The median progression-free survival was 5.7 months, and overall survival was 12.3 months. Conclusion Pemetrexed in combination with cisplatin demonstrates activity in the treatment of advanced, persistent, or recurrent carcinoma of the cervix.