bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin‐10 Gene Promoter and NFKB1 Promoter Insertion/Deletion Polymorphisms in Systemic Sclerosis
Authors: Salim P. H. , Jobim M. , Bredemeier M. , Chies J. A. B. , Brenol J. C. T. , Jobim L. F. , Xavier R. M. 
Published: December 2012

AbstractSystemic sclerosis (SSc) is a connective tissue disease characterized by fibrotic, immunological and vascular abnormalities. Nuclear factor‐kB (NFKB), as a key transcription factor involved in the regulation of immune responses, appears to be a good candidate for studies on the pathogenesis of autoimmune diseases, as well as the interleukin‐10 (IL‐10) polymorphism, which other studies have suggested an association with SSc. Our objective was to study the association of NFKB and IL‐10 gene polymorphisms with SSc. One hundred and fifty‐one SSc patients and 147 healthy bone marrow donors were enrolled in a case–control study. Blood was collected for DNA extraction; typing of IL‐10 genes was made by polymerase chain reaction with sequence‐specific primers (PCR–SSP), and NFKB gene typing was made by restriction fragment length polymorphism (RFLP). Patients underwent clinical evaluation, serology, Doppler echocardiography and chest high‐resolution computed tomography. The frequency of IL‐10 (−1082) GG genotype was found to be significantly higher in SSc patients (36.4%) as compared to healthy controls (22.4%) (P = 0.012). The frequency of heterozygous genotype GA was significantly lower (P = 0.004) in patients (38.4%) in comparison with control subjects (55.8%). A predominance of the high‐producing IL‐10 phenotype (GCC+/GCC+) was observed in SSc patients compared with healthy controls (37.7% versus 24.5%, respectively; OR: 1.87, 95% CI: 1.10–3.19, P = 0.019). No significant difference was found in the allelic and genotype distribution of the NFKB promoter polymorphism between patients and controls. No statistically significant associations were found between IL‐10 or NFKB polymorphisms clinical and laboratory features of SSc. Our results confirmed the association of the high‐producing phenotype (GCC+/GCC+) with increased risk for SSc, but found no correlation with NFKB polymorphisms.
Whither Tobacco Studies?
Authors: Bell Kirsten 
Published: December 2012

AbstractIn recent years, tobacco research has become an increasingly politicized field, with ‘legitimate’ research on this topic expected to further the goals of tobacco control. This paper presents an overview of the state of field of social science studies on tobacco and critiques the growing polarity evident in scholarship on this topic. Moving beyond mainstream public health perspectives, I outline a body of research that challenges dominant understandings of tobacco use and tobacco control. This research can be classified into three main categories: studies that interrogate conceptions of why people smoke, those that examine the impacts of tobacco control policy on smokers, and studies embracing intellectual and philosophical perspectives (especially phenomenology and social constructionism) that place them outside of a public health frame. I end with a broader discussion of the growing instrumentalization of social science research and the need to resist prescriptions that seek to dictate the appropriate form and content of scholarly work.
ScRALF3, a secreted RALF‐like peptide involved in cell–cell communication between the sporophyte and the female gametophyte in a solanaceous species
Authors: Chevalier Eric , Loubert‐Hudon Audrey , Matton Daniel P. 
Published: December 2012

SummarySmall peptides have been shown to regulate numerous aspects of plant development through cell–cell communication. These signaling events are particularly important during reproduction, regulating gamete development and embryogenesis. Rapid alkalinization factor (RALF)‐like genes, a large gene family that encodes secreted peptides, have specific or ubiquitous expression patterns. Previously, five RALF‐like genes with potential involvement during reproduction were isolated from Solanum chacoense. Here, we show that ScRALF3 is an important peptide regulator of female gametophyte development. Its expression, which is auxin‐inducible, is strictly regulated before and after fertilization. Down‐regulation of ScRALF3 expression by RNA interference leads to the production of smaller fruits that produce fewer seeds, due to improper development of the embryo sacs. Defects include loss of embryo sac nuclei polarization, as well as an increase in asynchronous division, accounting for cellular dysfunctions and premature embryo sac development arrest during megagametogenesis. ScRALF3 is expressed in the sporophytic tissue surrounding the embryo sac, the integument and the nucellus, as revealed by in situ hybridization and GUS staining. As expected for a secreted peptide, fluorescence from an ScRALF3–GFP fusion construct is detected throughout the secretory pathway. Therefore, the ScRALF3 secreted peptide may be directly involved in the regulation of multiple aspects of cell–cell communication between the female gametophyte and its surrounding sporophytic tissue during ovule development.
Dihedral Iwasawa theory of nearly ordinary quaternionic automorphic forms
Authors: Fouquet Olivier 
Published: December 2012

AbstractLetπ(f) be a nearly ordinary automorphic representation of the multiplicative group of an indefinite quaternion algebraBover a totally real fieldFwith associated Galois representationρf. LetKbe a totally complex quadratic extension ofFembedding inB. Using families of CM points on towers of Shimura curves attached toBandK, we construct an Euler system forρf. We prove that it extends top-adic families of Galois representations coming from Hida theory and dihedral ℤdp-extensions. When this Euler system is non-trivial, we prove divisibilities of characteristic ideals for the main conjecture in dihedral and modular Iwasawa theory.
Four‐dimensional dose evaluation using deformable image registration in radiotherapy for liver cancer
Authors: Hoon Jung Sang , Min Yoon Sang , Ho Park Sung , Cho Byungchul , Won Park Jae , Jung Jinhong , Park Jin‐hong , Hoon Kim Jong , Do Ahn Seung 
Published: December 2012

Purpose:In order to evaluate the dosimetric impact of respiratory motion on the dose delivered to the target volume and critical organs during free‐breathing radiotherapy, a four‐dimensional dose was evaluated using deformable image registration (DIR).Methods:Four‐dimensional computed tomography (4DCT) images were acquired for 11 patients who were treated for liver cancer. Internal target volume‐based treatment planning and dose calculation (3D dose) were performed using the end‐exhalation phase images. The four‐dimensional dose (4D dose) was calculated based on DIR of all phase images from 4DCT to the planned image. Dosimetric parameters from the 4D dose, were calculated and compared with those from the 3D dose.Results:There was no significant change of the dosimetric parameters for gross tumor volume (p > 0.05). The increase Dmean and generalized equivalent uniform dose (gEUD) for liver were by 3.1% ± 3.3% (p = 0.003) and 2.8% ± 3.3% (p = 0.008), respectively, and for duodenum, they were decreased by 15.7% ± 11.2% (p = 0.003) and 15.1% ± 11.0% (p = 0.003), respectively. The Dmax and gEUD for stomach was decreased by 5.3% ± 5.8% (p = 0.003) and 9.7% ± 8.7% (p = 0.003), respectively. The Dmax and gEUD for right kidney was decreased by 11.2% ± 16.2% (p = 0.003) and 14.9% ± 16.8% (p = 0.005), respectively. For left kidney, Dmax and gEUD were decreased by 11.4% ± 11.0% (p = 0.003) and 12.8% ± 12.1% (p = 0.005), respectively. The NTCP values for duodenum and stomach were decreased by 8.4% ± 5.8% (p = 0.003) and 17.2% ± 13.7% (p = 0.003), respectively.Conclusions:The four‐dimensional dose with a more realistic dose calculation accounting for respiratory motion revealed no significant difference in target coverage and potentially significant change in the physical and biological dosimetric parameters in normal organs during free‐breathing treatment.
Construction and Nonclinical Testing of a Puumala Virus Synthetic M Gene-Based DNA Vaccine
Authors: Brocato R. L. , Josleyn M. J. , Wahl-Jensen V. , Schmaljohn C. S. , Hooper J. W. 
Published: December 2012

ABSTRACTPuumala virus (PUUV) is a causative agent of hemorrhagic fever with renal syndrome (HFRS). Although PUUV-associated HFRS does not result in high case-fatality rates, the social and economic impact is considerable. There is no licensed vaccine or specific therapeutic to prevent or treat HFRS. Here we report the synthesis of a codon-optimized, full-length M segment open reading frame and its cloning into a DNA vaccine vector to produce the plasmid pWRG/PUU-M(s2). pWRG/PUU-M(s2) delivered by gene gun produced high-titer neutralizing antibodies in hamsters and nonhuman primates. Vaccination with pWRG/PUU-M(s2) protected hamsters against infection with PUUV but not against infection by related HFRS-associated hantaviruses. Unexpectedly, vaccination protected hamsters in a lethal disease model of Andes virus (ANDV) in the absence of ANDV cross-neutralizing antibodies. This is the first evidence that an experimental DNA vaccine for HFRS can provide protection in a hantavirus lethal disease model.
Kaposi's Sarcoma-Associated Herpesvirus Oncoprotein K13 Protects against B Cell Receptor-Induced Growth Arrest and Apoptosis through NF-κB Activation
Authors: Graham Ciaren , Matta Hittu , Yang Yanqiang , Yi Han , Suo Yulan , Tolani Bhairavi , Chaudhary Preet M. 
Published: December 2012

ABSTRACTKaposi's sarcoma-associated herpesvirus (KSHV) has been linked to the development of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease (MCD). We have characterized the role of KSHV-encoded viral FLICE inhibitory protein (vFLIP) K13 in the modulation of anti-IgM-induced growth arrest and apoptosis in B cells. We demonstrate that K13 protects WEHI 231, an immature B-cell line, against anti-IgM-induced growth arrest and apoptosis. The protective effect of K13 was associated with the activation of the NF-κB pathway and was deficient in a mutant K13 with three alanine substitutions at positions 58 to 60 (K13-58AAA) and a structural homolog, vFLIP E8, both of which lack NF-κB activity. K13 upregulated the expression of NF-κB subunit RelB and blocked the anti-IgM-induced decline in c-Myc and rise in p27Kip1that have been associated with growth arrest and apoptosis. K13 also upregulated the expression of Mcl-1, an antiapoptotic member of the Bcl2 family. Finally, K13 protected the mature B-cell line Ramos against anti-IgM-induced apoptosis through NF-κB activation. Inhibition of anti-IgM-induced apoptosis by K13 may contribute to the development of KSHV-associated lymphoproliferative disorders.
An AP-1 Binding Site in the Enhancer/Core Element of the HIV-1 Promoter Controls the Ability of HIV-1 To Establish Latent Infection
Authors: Duverger Alexandra , Wolschendorf Frank , Zhang Mingce , Wagner Fredric , Hatcher Brandon , Jones Jennifer , Cron Randall Q. , van der Sluis Renee M. , Jeeninga Rienk E. , Berkhout Ben , Kutsch Olaf 
Published: December 2012

ABSTRACTFollowing integration, HIV-1 in most cases produces active infection events; however, in some rare instances, latent infection events are established. The latter have major clinical implications, as latent infection allows the virus to persist despite antiretroviral therapy. Both the cellular factors and the viral elements that potentially determine whether HIV-1 establishes active or latent infection events remain largely elusive. We detail here the contribution of different long terminal repeat (LTR) sequences for the establishment of latent HIV-1 infection. Using a panel of full-length replication-competent virus constructs that reflect naturally occurring differences of HIV-1 subtype-specific LTRs and targeted LTR mutants, we found the primary ability of HIV-1 to establish latent infection in this system to be controlled by a four-nucleotide (nt) AP-1 element just upstream of the NF-κB element in the viral promoter. Deletion of this AP-1 site mostly deprived HIV-1 of the ability to establish latent HIV-1 infection. Extension of this site to a 7-nt AP-1 sequence massively promoted latency establishment, suggesting that this promoter region represents a latency establishment element (LEE). Given that these minimal changes in a transcription factor binding site affect latency establishment to such large extent, our data support the notion that HIV-1 latency is a transcription factor restriction phenomenon.
No Evidence of Xenotropic Murine Leukemia Virus-Related Virus Transmission by Blood Transfusion from Infected Rhesus Macaques
Authors: Williams Dhanya K. , Galvin Teresa A. , Gao Yamei , O'Neill Christina , Glasner Dustin , Khan Arifa S. 
Published: December 2012

ABSTRACT

The discovery of xenotropic murine leukemia virus-related virus (XMRV) in human tissue samples has been shown to be due to virus contamination with a recombinant murine retrovirus. However, due to the unknown pathogenicity of this novel retrovirus and its broad host range, including human cell lines, it is important to understand the modes of virus transmission and develop mitigation and management strategies to reduce the risk of human exposure and infection. XMRV transmission was evaluated by whole-blood transfusion in rhesus macaques. Monkeys were infected with XMRV to serve as donor monkeys for blood transfers at weeks 1, 2, and 3 into naïve animals. The donor and recipient monkeys were evaluated for XMRV infection by nested PCR assays with nucleotide sequence confirmation, Western blot assays for development of virus-specific antibodies, and coculture of monkey peripheral blood mononuclear cells (PBMCs) with a sensitive target cell line for virus isolation. XMRV infection was demonstrated in the virus-injected donor monkeys, but there was no evidence of virus transmission by whole-blood transfusion to naïve monkeys based upon PCR analysis of PBMCs using XMRV-specific
gag
and
env
primers, Western blot analysis of monkey plasma up to 31 to 32 weeks after transfusion, and coculture studies using monkey PBMCs from various times after transfusion. The study demonstrates the lack of XMRV transmission by whole-blood transfusion during the acute phase of infection. Furthermore, analysis of PBMC viral DNA showed extensive APOBEC-mediated G-to-A hypermutation in a donor animal at week 9, corroborating previous results using macaques and supporting the possible restriction of XMRV replication in humans by a similar mechanism.
Intragenic Complementation of Hepatitis C Virus NS5A RNA Replication-Defective Alleles
Authors: Fridell Robert A. , Valera Lourdes , Qiu Dike , Kirk Melissa J. , Wang Chunfu , Gao Min 
Published: December 2012

ABSTRACT

Hepatitis C virus NS5A has three structural domains, is required for RNA replication and virion assembly, and exists in hypo- and hyperphosphorylated forms. Accumulated data suggest that phosphorylation is involved in modulating NS5A functions. We performed a mutational analysis of highly conserved serine residues in the linker region between domains I and II of genotype 2a JFH1 NS5A. As with genotype 1b Con1 NS5A, we found that specific serine residues were important for efficient hyperphosphorylation of JFH1 NS5A. However, in contrast with Con1 replicons, we observed a positive correlation between hyperphosphorylation and JFH1 replicon replication. We previously demonstrated
trans
-complementation of a hyperphosphorylation-deficient, replication-defective JFH1 replicon. Our results suggested that the defective NS5A encoded by this replicon, while lacking one NS5A function, was capable of performing a separate replication function. In this report, we examined an additional set of replication-defective NS5A mutations in
trans
-complementation assays. While some behaved similarly to the S232I replicon, others displayed a unique
trans
-complementation phenotype, suggesting that NS5A
trans
-complementation can occur by two distinct modes. Moreover, we were able, for the first time, to demonstrate intragenic complementation of replication-defective NS5A alleles. Our results identified three complementation groups: group A, comprising mutations within NS5A domain I; group B, comprising mutations affecting serine residues important for hyperphosphorylation and a subset of the domain I mutations; and group C, comprising a single mutation within the C-terminal region of domain II. We postulate that these complementation groups define three distinct and genetically separable functions of NS5A in RNA replication.
A Novel Bacterium-Free Method for Generation of Flavivirus Infectious DNA by Circular Polymerase Extension Reaction Allows Accurate Recapitulation of Viral Heterogeneity
Authors: Edmonds Judith , van Grinsven Erinke , Prow Natalie , Bosco-Lauth Angela , Brault Aaron C. , Bowen Richard A. , Hall Roy A. , Khromykh Alexander A. 
Published: December 2012

ABSTRACT
A novel bacterium-free approach for rapid assembly of flavivirus infectious cDNAs using circular polymerase extension reaction was applied to generate infectious cDNA for the virulent New South Wales isolate of the Kunjin strain of West Nile virus (KUNV) that recently emerged in Australia. Recovered virus recapitulated the genetic heterogeneity present in the original isolate. The approach was utilized to generate viral mutants with designed phenotypic properties and to identify E protein glycosylation as one of the virulence determinants.
Predictors of repeatChlamydia trachomatisand/orNeisseria gonorrhoeaeinfections among African-American adolescent women
Authors: Swartzendruber Andrea , Sales Jessica M , Brown Jennifer L , Davis Teaniese Latham , DiClemente Ralph J , Rose Eve 
Published: December 2012

BackgroundYoung African-American women have the highest rates ofChlamydia trachomatisandNeisseria gonorrhoeaein the USA. The objective was to identify baseline predictors of repeat chlamydia and/or gonorrhoea infections among African-American adolescent women.MethodsSociodemographic, psychosocial and behavioural data were collected at baseline and every 6 months for 2 years from 701 African-American women (14–20 years) enrolled in an HIV prevention trial. Vaginal swabs were self-collected at each visit and assayed for chlamydia and gonorrhoea using DNA amplification. Among participants testing positive for chlamydia and/or gonorrhoea at baseline, logistic regression analyses assessed baseline predictors of repeat infection.ResultsOf 618 (88%) participants with ≥1 follow-up assessment, 123 (20%) had a positive chlamydia and/or gonorrhoea test result at baseline; 49 (40%) had a repeat infection during the study period. Of those with a repeat infection, 30 (61%) were positive at one follow-up visit, 18 (37%) at two visits and 1 (2%) at three follow-up visits. Controlling for age and intervention condition, impulsivity (AOR: 1.71, p=0.018) was associated with an increased likelihood, and having a boyfriend (AOR: 0.21, p=0.006) was associated with a decreased likelihood of repeat infection.ConclusionsRepeat chlamydia and/or gonorrhoea infections are common among African-American adolescent women. Among young African-American women who test positive for chlamydia and/or gonorrhoea, tailored interventions for more impulsive adolescents and those not in a relationship may reduce risk of repeat infections. Given the high numbers of repeat infections after receipt of an evidence-based intervention, enhanced screening and treatment services for young men may be warranted.Clinical Trials Registrationhttp://www.clinicaltrials.gov(NCT00279799)
Antibacterial, antioxidant and cytotoxic studies of total saponin, alkaloid and sterols contents of decoction of Joshanda
Authors: Khan Haroon , Khan Murad Ali , Abdullah  
Published: December 2012

The current study was aimed to assess antibacterial, antioxidant and cytotoxic activity of total saponin, alkaloid and sterol contents of Joshanda decoction followed by its constituent’s analysis via thin layer chromatography (TLC). Saponins and alkaloids showed prominent antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Bacillus cereus and Klebsiella pneumoniae whereas sterols only against S. aureus. Saponin and alkaloid contents of 97 and 108 µg/ml, respectively, showed prominent free radical scavenging activity against 1,1-diphenyl-2-picrylhidrazyl, with mild cytotoxicity in brine shrimp cytotoxic test. Under ultraviolet light at 254 nm, TLC of total saponins showed eight different compounds, total sterols comprising three while total alkaloids two compounds of various polarities. It is concluded that the various contents of Joshanda decoction possess outstanding susceptibility against bacteria implicating primarily upper respiratory tract infections augmented by strong antioxidant activity.
Functional relevance of dynamic properties of Dimeric NADP-dependent Isocitrate Dehydrogenases
Authors: Vinekar Rithvik , Verma Chandra , Ghosh Indira 
Published: December 2012

Abstract

Background
Isocitrate Dehydrogenases (IDHs) are important enzymes present in all living cells. Three subfamilies of functionally dimeric IDHs (subfamilies I, II, III) are known. Subfamily I are well-studied bacterial IDHs, like that of Escherischia coli. Subfamily II has predominantly eukaryotic members, but it also has several bacterial members, many being pathogens or endosymbionts. subfamily III IDHs are NAD-dependent.
The eukaryotic-like subfamily II IDH from pathogenic bacteria such as Mycobacterium tuberculosis IDH1 are expected to have regulation similar to that of bacteria which use the glyoxylate bypass to survive starvation. Yet they are structurally different from IDHs of subfamily I, such as the E. coli IDH.

Results
We have used phylogeny, structural comparisons and molecular dynamics simulations to highlight the similarity and differences between NADP-dependent dimeric IDHs with an emphasis on regulation. Our phylogenetic study indicates that an additional subfamily (IV) may also be present. Variation in sequence and structure in an aligned region may indicate functional importance concerning regulation in bacterial subfamily I IDHs.
Correlation in movement of prominent loops seen from molecular dynamics may explain the adaptability and diversity of the predominantly eukaryotic subfamily II IDHs.

Conclusion
This study discusses possible regulatory mechanisms operating in various IDHs and implications for regulation of eukaryotic-like bacterial IDHs such as that of M. tuberculosis, which may provide avenues for intervention in disease.