bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fast rewarming after deep hypothermic circulatory arrest in rats impairs histologic outcome and increases NFκB expression in the brain
Authors: Gordan M Lucia , Kellermann Kristine , Blobner Manfred , Nollert Georg , Kochs Eberhard F , Jungwirth Bettina 
Published: July 2010

Objective: Deep hypothermia is used as a neuroprotectant during cardiac surgery utilizing deep hypothermic circulatory arrest (DHCA), although the ideal rewarming strategy is not known yet. Some of the neuroprotective properties of hypothermia seem to be mediated by Nuclear Factor Kappa B (NFκB) as an important transcription factor. The current study was designed to investigate the effect of the rewarming rate on histologic outcome and cerebral NFκB expression one day following DHCA in rats. Methods: With IRB approval, 20 rats were cannulated for cardiopulmonary bypass (CPB), cooled to a rectal temperature of 15-18°C, subjected to 45min of DHCA and randomly assigned to either a slow (40 min) or a fast (20 min) rewarming protocol. At 24 hours post DHCA, the number of eosinophilic neurons was analyzed with hematoxylin and eosin (HE) staining, and NFκB expression immunohistochemically. The two experimental groups were compared with untreated control rats. Results: HE staining showed more eosinophilic neurons in the motor cortex following fast rewarming (60 [15-388]) compared to slow rewarming (15 [10—21]) (p<0.05). Neuronal expression of NFκB was increased in the fast rewarming group in both brain areas, the motor cortex (fast: 258 [135-393]; slow: 165 [80—212]; control: 73 [44-111]) as well as the hippocampus (fast: 243 [209-314]; slow: 202 [187-239]; control: 86 [68-108]) (p<0.05). Hyperthermic episodes were strictly avoided. Conclusions: Fast rewarming with strict avoidance of hyperthermia after DHCA in rats was accompanied by pronounced histologic damage and accentuated cerebral NFκB expression.
Persistent microalbuminuria after treatment with renin-angiotensin axis blockers: causes and results of treatment intensification
Authors: Robles NR , Velasco J. , Espinosa J. , Mena C. , Angulo E. , MICREX Group Investigators  
Published: July 2010

Aims: The first phase of this study aimed to determine the causes of persistent microalbuminuria after treatment with renin—angiotensin axis (RAA) blocking drugs. In a second phase we tried to determine if strict control of blood pressure and intensive RAA blockade could induce remission or reduction of microalbuminuria in clinical (primary care) practice. Patients and methods: The study included both diabetic patients and non-diabetic hypertensive patients treated with RAA drugs in the presence of microalbuminuria. 211 patients were recruited (mean age 66.6±11.3 years, 111 men, 117 were diabetic). In the first phase treatment was optimized at standard doses. In the second phase treatment was increased during a three months period to reach a blood pressure (BP) < 130/80 mmHg by adding other antihypertensive treatment and to obtain maximal RAA blockade using long-acting drugs, increased dosage, or adding further medication at night. Results: Initial mean BP was 141±16/81±11 mmHg. BP control was unsatisfactory (control of systolic blood pressure [SBP] 19.3%; diastolic blood pressure [DBP] 37.6%). Dosage of RAA blocking drugs was inadequate in 21% of patients. Only 27.4% of patients were taking antihypertensive drugs at night. 30.1% of patients took once daily short acting drugs. During the studymean SBP was reduced to 137±13 mmHg (p < .001) and DBP decreased to 79±10 mmHg (p < .001). Control of SBP improved to 24.5% and DBP control went to 44.4%. Mean microalbuminuria decreased from 64.4±47.0 mg/day to 50.1±53.0 mg/day (p < .001) and the prevalence of microalbuminuria was reduced to 59.1%. Conclusions: Persistent microalbuminuria was associated with poor blood pressure control and inadequate drug dosage. Low frequency of administration of drugs at night and inappropriate once-daily pills intake were frequent. Strict control of blood pressure and intensive RAA blockade significantly reduced the prevalence of microalbuminuria.
Analysis of concrete internal deterioration due to frost action
Authors: Wardeh George , Mohamed Mohamed AS , Ghorbel Elhem 
Published: July 2010

This study concerns the frost durability of an ordinary concrete without air-entraining agents. The water—cement ratio and the quantity of cement were chosen within the limitations imposed by the French standard. Physical and mechanical characteristics evolutions during freezing—thawing cycles have been followed. The obtained results show that the reduction in the mechanical resistance and the elastic modulus is accompanied by an increase in the intrinsic permeability. The damage is characterized by a scalar parameter, Df, due to frost action with which the resistance reduction as well as the permeability evolution may be described as a function of crack development. The pore liquid phase pressure, generated during ice formation, was also calculated by an inverse poroelastic analysis based on strains recorded during freezing—thawing cycles. A negative pore pressure of 25 MPa at a temperature of -15° C resulting in an effective stress representing 25% of the compressive strength was found.
The ADAMTS13 metalloprotease domain: roles of subsites in enzyme activity and specificity
Authors: de Groot Rens , Lane David A. , Crawley James T. B. 
Published: July 2010

AbstractADAMTS13 modulates von Willebrand factor (VWF) platelet-tethering function by proteolysis of the Tyr1605-Met1606 bond in the VWF A2 domain. To examine the role of the metalloprotease domain of ADAMTS13 in scissile bond specificity, we identified 3 variable regions (VR1, -2, and -3) in the ADAMTS family metalloprotease domain that flank the active site, which might be important for specificity. Eight composite sequence swaps (to residues in ADAMTS1 or ADAMTS2) and 18 single-point mutants were generated in these VRs and expressed. Swapping VR1 (E184-R193) of ADAMTS13 with that of ADAMTS1 or ADAMTS2 abolished/severely impaired ADAMTS13 function. Kinetic analysis of VR1 point mutants using VWF115 as a short substrate revealed reduced proteolytic function (kcat/Km reduced by 2- to 10-fold) as a result of D187A, R190A, and R193A substitutions. Analysis of VR2 (F216-V220) revealed a minor importance of this region. Mutants of VR3 (G236-A261) proteolysed wild-type VWF115 normally. However, using either short or full-length VWF substrates containing the P1′ M1606A mutation, we identified residues within VR3 (D252-P256) that influence P1′ amino acid specificity, we hypothesize, by shaping the S1′ pocket. It is concluded that 2 subsites, D187-R193 and D252-P256, in the metalloprotease domain play an important role in cleavage efficiency and site specificity.
A prospective study of Epstein-Barr virus antibodies and risk of non-Hodgkin lymphoma
Authors: Bertrand Kimberly A. , Birmann Brenda M. , Chang Ellen T. , Spiegelman Donna , Aster Jon C. , Zhang Shumin M. , Laden Francine 
Published: July 2010

AbstractSevere immunosuppression is an established risk factor for non-Hodgkin lymphoma (NHL), but an association with subclinical immune dysfunction is unclear. We conducted a case-control study nested in the Physicians' Health Study and the Nurses' Health Study cohorts to determine whether patterns of antibody response to Epstein-Barr virus (EBV) were associated with NHL risk. We measured antibody titers against viral capsid antigen, early antigen, and Epstein-Barr nuclear antigen (EBNA-1 and EBNA-2) in blood samples collected before diagnosis from 340 cases and 662 matched controls. Using conditional logistic regression, we estimated rate ratios (RRs) and 95% confidence intervals (CIs) for elevated versus normal titers and the ratio of anti–EBNA-1 to anti–EBNA-2 titers (≤ 1.0 vs > 1.0). We found no association between EBV serostatus, elevated titers, or an EBNA-1/EBNA-2 ratio ≤ 1.0 and NHL risk overall. For chronic lymphocytic leukemia/small lymphocytic lymphoma, suggestive associations were noted for elevated anti–EBNA-2 (RR, 1.74; 95% CI, 0.99-3.05), anti–viral capsid antigen (RR, 1.58; 95% CI, 0.79-3.14), and EBNA-1/EBNA-2 ratio ≤ 1.0 (RR, 1.52; 95% CI, 0.91-2.55). There was no evidence of heterogeneity by subtype. Overall, we found no evidence that EBV antibody profile predicts NHL risk in immunocompetent persons, with the possible exception of chronic lymphocytic leukemia/small lymphocytic lymphoma.
Animal model of fetal and neonatal immune thrombocytopenia: role of neonatal Fc receptor in the pathogenesis and therapy
Authors: Chen Pingguo , Li Conglei , Lang Sean , Zhu Guangheng , Reheman Adili , Spring Christopher M. , Freedman John , Ni Heyu 
Published: July 2010

AbstractFetal and neonatal immune thrombocytopenia (FNIT) is a severe bleeding disorder in which maternal antibodies cross the placenta and destroy fetal/neonatal platelets. It has been demonstrated that the neonatal Fc receptor (FcRn) regulates immunoglobulin G (IgG) homeostasis and plays an important role in transplacental IgG transport. However, the role of FcRn in the pathogenesis and therapy of FNIT has not been studied. Here, we developed an animal model of FNIT using combined β3 integrin–deficient and FcRn-deficient (β3−/−FcRn−/−) mice. We found that β3−/−FcRn−/− mice are immunoresponsive to β3+/+FcRn−/− platelets. The generated antibodies were β3 integrin specific and were maintained at levels that efficiently induced thrombocytopenia in adult β3+/+FcRn−/− mice. FNIT was observed when immunized β3−/−FcRn+/+ females were bred with β3+/+FcRn+/+ males, while no FNIT occurred in β3−/−FcRn−/− females bred with β3+/+FcRn−/− males, suggesting that FcRn is indispensable for the induction of FNIT. We further demonstrated that fetal FcRn was responsible for the transplacental transport of various IgG isotypes. We found that anti-FcRn antibody and intravenous IgG prevented FNIT, and that intravenous IgG ameliorated FNIT through both FcRn-dependent and -independent pathways. Our data suggest that targeting FcRn may be a potential therapy for human FNIT as well as other maternal pathogenic antibody-mediated diseases.
Epigenetic silencing of BIM in glucocorticoid poor-responsive pediatric acute lymphoblastic leukemia, and its reversal by histone deacetylase inhibition
Authors: Bachmann Petra S. , Piazza Rocco G. , Janes Mary E. , Wong Nicholas C. , Davies Carwyn , Mogavero Angela , Bhadri Vivek A. , Szymanska Barbara , Geninson Greta , Magistroni Vera , Cazzaniga Giovanni , Biondi Andrea , Miranda-Saavedra Diego , Göttgens Berthold , Saffery Richard , Craig Jeffrey M. , Marshall Glenn M. , Gambacorti-Passerini Carlo , Pimanda John E. , Lock Richard B. 
Published: July 2010

Abstract
Glucocorticoids play a critical role in the therapy of lymphoid malignancies, including pediatric acute lymphoblastic leukemia (ALL), although the mechanisms underlying cellular resistance remain unclear. We report glucocorticoid resistance attributable to epigenetic silencing of the BIM gene in pediatric ALL biopsies and xenografts established in immune-deficient mice from direct patient explants as well as a therapeutic approach to reverse resistance in vivo. Glucocorticoid resistance in ALL xenografts was consistently associated with failure to up-regulate BIM expression after dexamethasone exposure despite confirmation of a functional glucocorticoid receptor. Although a comprehensive assessment of BIM CpG island methylation revealed no consistent changes, glucocorticoid resistance in xenografts and patient biopsies significantly correlated with decreased histone H3 acetylation. Moreover, the histone deacetylase inhibitor vorinostat relieved BIM repression and exerted synergistic antileukemic efficacy with dexamethasone in vitro and in vivo. These findings provide a novel therapeutic strategy to reverse glucocorticoid resistance and improve outcome for high-risk pediatric ALL.
Mechanisms of haplotype divergence at the RGA08 nucleotide-binding leucine-rich repeat gene locus in wild banana (Musa balbisiana)
Authors: Baurens Franc-Christophe , Bocs Stéphanie , Rouard Mathieu , Matsumoto Takashi , Miller Robert NG , Rodier-Goud Marguerite , MBéguié-A-MBéguié Didier , Yahiaoui Nabila 
Published: July 2010

Abstract

Background
Comparative sequence analysis of complex loci such as resistance gene analog clusters allows estimating the degree of sequence conservation and mechanisms of divergence at the intraspecies level. In banana (Musa sp.), two diploid wild species Musa acuminata (A genome) and Musa balbisiana (B genome) contribute to the polyploid genome of many cultivars. The M. balbisiana species is associated with vigour and tolerance to pests and disease and little is known on the genome structure and haplotype diversity within this species. Here, we compare two genomic sequences of 253 and 223 kb corresponding to two haplotypes of the RGA08 resistance gene analog locus in M. balbisiana "Pisang Klutuk Wulung" (PKW).

Results
Sequence comparison revealed two regions of contrasting features. The first is a highly colinear gene-rich region where the two haplotypes diverge only by single nucleotide polymorphisms and two repetitive element insertions. The second corresponds to a large cluster of RGA08 genes, with 13 and 18 predicted RGA genes and pseudogenes spread over 131 and 152 kb respectively on each haplotype. The RGA08 cluster is enriched in repetitive element insertions, in duplicated non-coding intergenic sequences including low complexity regions and shows structural variations between haplotypes. Although some allelic relationships are retained, a large diversity of RGA08 genes occurs in this single M. balbisiana genotype, with several RGA08 paralogs specific to each haplotype. The RGA08 gene family has evolved by mechanisms of unequal recombination, intragenic sequence exchange and diversifying selection. An unequal recombination event taking place between duplicated non-coding intergenic sequences resulted in a different RGA08 gene content between haplotypes pointing out the role of such duplicated regions in the evolution of RGA clusters. Based on the synonymous substitution rate in coding sequences, we estimated a 1 million year divergence time for these M. balbisiana haplotypes.

Conclusions
A large RGA08 gene cluster identified in wild banana corresponds to a highly variable genomic region between haplotypes surrounded by conserved flanking regions. High level of sequence identity (70 to 99%) of the genic and intergenic regions suggests a recent and rapid evolution of this cluster in M. balbisiana.
Toll-Like Receptor (TLR) and Nucleosome-binding Oligomerization Domain (NOD) gene polymorphisms and endometrial cancer risk
Authors: Ashton Katie A , Proietto Anthony , Otton Geoffrey , Symonds Ian , McEvoy Mark , Attia John , Scott Rodney J 
Published: July 2010

Abstract

Background
Endometrial cancer is the most common gynaecological malignancy in women of developed countries. Many risk factors implicated in endometrial cancer trigger inflammatory events; therefore, alterations in immune response may predispose an individual to disease. Toll-like receptors (TLRs) and nucleosome-binding oligomerization domain (NOD) genes are integral to the recognition of pathogens and are highly polymorphic. For these reasons, the aim of the study was to assess the frequency of polymorphic variants in TLR and NOD genes in an Australian endometrial cancer population.

Methods
Ten polymorphisms were genotyped in 191 endometrial cancer cases and 291 controls using real-time PCR: NOD1 (rs2075822, rs2907749, rs2907748), NOD2 (rs5743260, rs2066844, rs2066845), TLR2 (rs5743708), TLR4 (rs4986790) and TLR9 (rs5743836, rs187084).

Results
Haplotype analysis revealed that the combination of the variant alleles of the two TLR9 polymorphisms, rs5743836 and rs187084, were protective for endometrial cancer risk: OR 0.11, 95% CI (0.03-0.44), p = 0.002. This result remained highly significant after adjustment for endometrial cancer risk factors and Bonferroni correction for multiple testing. There were no other associations observed for the other polymorphisms in TLR2, TLR4, NOD1 and NOD2.

Conclusions
The variant 'C' allele of rs5743836 causes greater TLR9 transcriptional activity compared to the 'T' allele, therefore, higher TLR9 activity may be related to efficient removal of microbial pathogens within the endometrium. Clearly, the association of these TLR9 polymorphisms and endometrial cancer risk must be further examined in an independent population. The results point towards the importance of examining immune response in endometrial tumourigenesis to understand new pathways that may be implicated in disease.
Gamma knife radiosurgery for movement disorders: a concise review of the literature
Authors: Elaimy Ameer L , Arthurs Benjamin J , Lamoreaux Wayne T , Demakas John J , Mackay Alexander R , Fairbanks Robert K , Greeley David R , Cooke Barton S , Lee Christopher M 
Published: July 2010

Abstract
Medication is the predominant method for the management of patients with movement disorders. However, there is a fraction of patients who experience limited relief from pharmaceuticals or experience bothersome side-effects of the drugs. Deep brain stimulation (DBS) and surgical lesioning of the thalamus and basal ganglia are respected neurosurgical procedures, with valued success rates and a very low incidence of complications. Despite these positive outcomes, DBS and surgical lesioning procedures are contraindicated for some patients. Stereotactic radiosurgery with the Gamma Knife (GK) has been used as a lesioning technique for patients seeking a non-invasive treatment alternative and for medication-intolerable patients, who are unable to undergo DBS or lesioning due to comorbid medical conditions. Tremors of various etiologies are treated using GK thalamotomy, which targets the ventralis intermedius nucleus. GK thalamotomy produces favorable outcomes when treating tremors, with success rates ranging from 80-100%. In contrast, GK pallidotomy targets the internal globus pallidus, and is used in treating bradykinesia, rigidity, and dyskinesia. Although radiosurgery has proven beneficial for tremors, radiosurgical pallidotomy for bradykinesia, rigidity, and dyskinesia remains questionable, with mixed success rates in the literature that ranges from 0-87%. We suggest that GK thalamotomy be offered along with other neurosurgical approaches as a feasible treatment option to patients who prefer the non-invasive nature of radiosurgery and to those who are unqualified candidates for the neurosurgical alternatives. Also, we advise that patients with bradykinesia, rigidity, and dyskinesia be educated about the variability in the literature pertaining to GK pallidotomy before proceeding with treatment.
Co-receptor tropism prediction among 1045 Indian HIV-1 subtype C sequences: Therapeutic implications for India
Authors: Neogi Ujjwal , Prarthana Sreenivasa B , D'Souza George , DeCosta Ayesha , Kuttiatt Vijesh S , Ranga Udaykumar , Shet Anita 
Published: July 2010

AbstractBackgroundUnderstanding co-receptor tropism of HIV-1 strains circulating in India will provide key analytical leverage for assessing the potential usefulness of newer antiretroviral drugs such as chemokine co-receptor antagonists among Indian HIV-infected populations. The objective of this study was to determine usingin silicomethods, HIV-1 tropism among a large number of Indian isolates both from primary clinical isolates as well as from database-derived sequences.ResultsR5-tropism was seen in 96.8% of a total of 1045 HIV-1 subtype C Indian sequences. Co-receptor prediction of 15 primary clinical isolates detected two X4-tropic strains using the C-PSSM matrix. R5-tropic HIV-1 subtype C V3 sequences were conserved to a greater extent than X4-tropic strains. X4-tropic strains were obtained from subjects who had a significantly longer time since HIV diagnosis (96.5 months) compared to R5-tropic strains (20.5 months).ConclusionsHigh prevalence of R5 tropism and greater homogeneity of the V3 sequence among HIV-1 subtype C strains in India suggests the potential benefit of CCR5 antagonists as a therapeutic option in India.
Expressing gK gene of duck enteritis virus guided by bioinformatics and its applied prospect in diagnosis
Authors: Zhang Shunchuan , Ma Guangpeng , Xiang Jun , Cheng Anchun , Wang Mingshu , Zhu Dekang , Jia Renyong , Luo Qihui , Chen Zhengli , Chen Xiaoyue 
Published: July 2010

Abstract

Background
Duck viral enteritis, which is caused by duck enteritis virus (DEV), causes significant economic losses in domestic and wild waterfowls because of the high mortality and low egg production rates. With the purpose of eliminating this disease and decreasing economic loss in the commercial duck industry, researching on glycoprotein K (gK) of DEV may be a new kind of method for preventing and curing this disease. Because glycoproteins project from the virus envelope as spikes and are directly involved in the host immune system and elicitation of the host immune responses, and also play an important role in mediating infection of target cells, the entry into cell for free virus and the maturation or egress of virus. The gK is one of the major envelope glycoproteins of DEV. However, little information correlated with gK is known, such as antigenic and functional characterization.

Results
Bioinformatic predictions revealed that the expression of the full-length gK gene (fgK) in a prokaryotic system is difficult because of the presence of suboptimal exon and transmembrane domains at the C-terminal. In this study, we found that the fgK gene might not be expressed in a prokaryotic system in accordance with the bioinformatic predictions. Further, we successfully used bioinformatics tools to guide the prokaryotic expression of the gK gene by designing a novel truncated gK gene (tgK). These findings indicated that bioinformatics provides theoretical data for target gene expression and saves time for our research. The recombinant tgK protein (tgK) was expressed and purified by immobilized metal affinity chromatography (IMAC). Western blotting and indirect enzyme-linked immunosorbent assay (ELISA) showed that the tgK possessed antigenic characteristics similar to native DEV-gK.

Conclusions
In this work, the DEV-tgK was expressed successfully in prokaryotic system for the first time, which will provide usefull information for prokaryotic expression of alphaherpesvirus gK homologs, and the recombinant truncated gK possessed antigenic characteristics similar to native DEV gK. Because of the good reactionogenicity, specificity and sensitivity, the purified tgK could be useful for developing a sensitive serum diagnostic kit to monitor DEV outbreaks.