bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fine-Mapping in African Americans of 8 Recently Discovered Genetic Loci for Plasma Lipids
Authors: Keebler Mary E. , Deo Rahul C. , Surti Aarti , Konieczkowski David , Guiducci Candace , Burtt Noel , Buxbaum Sarah G. , Sarpong Daniel F. , Steffes Michael W. , Wilson James G. , Taylor Herman A. , Kathiresan Sekar 
Published: June 2010

Background—
Genome-wide association studies in cohorts of European descent have identified novel genomic regions as associated with lipids, but their relevance in African Americans remains unclear.

Methods and Results—

We genotyped 8 index single nucleotide polymorphisms (SNPs) and 488 tagging SNPs across 8 novel lipid loci in the Jackson Heart Study, a community-based cohort of 4605 African Americans. For each trait, we calculated residuals adjusted for age, sex, and global ancestry and performed multivariable linear regression to detect genotype-phenotype association with adjustment for local ancestry. To explore admixture effects, we conducted stratified analyses in individuals with a high probability of 2 African ancestral alleles or at least 1 European allele at each locus. We confirmed 2 index SNPs as associated with lipid traits in African Americans, with suggestive association for 3 more. However, the effect sizes for 4 of the 5 associated SNPs were larger in the European local ancestry subgroup compared with the African local ancestry subgroup, suggesting that the replication is driven by European ancestry segments. Through fine-mapping, we discovered 3 new SNPs with significant associations, 2 with consistent effect on triglyceride levels across ancestral groups: rs636523 near
DOCK7
/
ANGPTL3
and rs780093 in
GCKR
. African linkage disequilibrium patterns did not assist in narrowing association signals.

Conclusions—
We confirm that 5 genetic regions associated with lipid traits in European-derived populations are relevant in African Americans. To further evaluate these loci, fine-mapping in larger African American cohorts and/or resequencing will be required.
A clinical trial of peer-based culturally responsive person-centered care for psychosis for African Americans and Latinos
Authors: Tondora Janis , O'Connell Maria , Miller Rebecca , Dinzeo Tom , Bellamy Chyrell , Andres-Hyman Raquel , Davidson Larry 
Published: June 2010

Background Providing culturally competent and person-centered care is at the forefront of changing practices in behavioral health. Significant health disparities remain between people of color and whites in terms of care received in the mental health system. Peer services, or support provided by others who have experience in the behavioral health system, is a promising new avenue for helping those with behavioral health concerns move forward in their lives. Purpose We describe a model of peer-based culturally competent person-centered care and treatment planning, informed by longstanding research on recovery from serious mental illness used in a randomized clinical trial conducted at two community mental health centers. Methods Participants all were Latino or African American with a current or past diagnosis within the psychotic disorders spectrum as this population is often underserved with limited access to culturally responsive, person-centered services. Study interventions were carried out in both an English-speaking and a Spanish-speaking outpatient program at each study center. Interventions included connecting individuals to their communities of choice and providing assistance in preparing for treatment planning meetings, all delivered by peer-service providers. Three points of evaluation, at baseline, 6 and 18 months, explored the impact of the interventions on areas such as community engagement, satisfaction with treatment, symptom distress, ethnic identity, personal empowerment, and quality of life. Conclusions Lessons learned from implementation include making cultural modifications, the need for a longer engagement period with participants, and the tension between maintaining strict interventions while addressing the individual needs of participants in line with person-centered principles. The study is one of the first to rigorously test peer-supported interventions in implementing person-centered care within the context of public mental health systems. Clinical Trials 2010; 7: 368—379. http://ctj.sagepub.com
Reversion of epigenetically mediated BIM silencing overcomes chemoresistance in Burkitt lymphoma
Authors: Richter-Larrea Jose A. , Robles Eloy F. , Fresquet Vicente , Beltran Elena , Rullan Antonio J. , Agirre Xabier , Calasanz Maria José , Panizo Carlos , Richter Jose A. , Hernandez Jesus M. , Roman-Gomez Jose , Prosper Felipe , Martinez-Climent Jose A. 
Published: June 2010

AbstractIn Burkitt lymphoma/leukemia (BL), achievement of complete remission with first-line chemotherapy remains a challenging issue, as most patients who respond remain disease-free, whereas those refractory have few options of being rescued with salvage therapies. The mechanisms underlying BL chemoresistance and how it can be circumvented remain undetermined. We previously reported the frequent inactivation of the proapoptotic BIM gene in B-cell lymphomas. Here we show that BIM epigenetic silencing by concurrent promoter hypermethylation and deacetylation occurs frequently in primary BL samples and BL-derived cell lines. Remarkably, patients with BL with hypermethylated BIM presented lower complete remission rate (24% vs 79%; P = .002) and shorter overall survival (P = .007) than those with BIM-expressing lymphomas, indicating that BIM transcriptional repression may mediate tumor chemoresistance. Accordingly, by combining in vitro and in vivo studies of human BL-xenografts grown in immunodeficient RAG2−/−γc−/− mice and of murine B220+IgM+ B-cell lymphomas generated in Eμ-MYC and Eμ-MYC-BIM+/− transgenes, we demonstrate that lymphoma chemoresistance is dictated by BIM gene dosage and is reversible on BIM reactivation by genetic manipulation or after treatment with histone-deacetylase inhibitors. We suggest that the combination of histone-deacetylase inhibitors and high-dose chemotherapy may overcome chemoresistance, achieve durable remission, and improve survival of patients with BL.
Genome size evolution in pufferfish: an insight from BAC clone-based Diodon holocanthus genome sequencing
Authors: Guo Baocheng , Zou Ming , Gan Xiaoni , He Shunping 
Published: June 2010

Abstract

Background
Variations in genome size within and between species have been observed since the 1950 s in diverse taxonomic groups. Serving as model organisms, smooth pufferfish possess the smallest vertebrate genomes. Interestingly, spiny pufferfish from its sister family have genome twice as large as smooth pufferfish. Therefore, comparative genomic analysis between smooth pufferfish and spiny pufferfish is useful for our understanding of genome size evolution in pufferfish.

Results
Ten BAC clones of a spiny pufferfish Diodon holocanthus were randomly selected and shotgun sequenced. In total, 776 kb of non-redundant sequences without gap representing 0.1% of the D. holocanthus genome were identified, and 77 distinct genes were predicted. In the sequenced D. holocanthus genome, 364 kb is homologous with 265 kb of the Takifugu rubripes genome, and 223 kb is homologous with 148 kb of the Tetraodon nigroviridis genome. The repetitive DNA accounts for 8% of the sequenced D. holocanthus genome, which is higher than that in the T. rubripes genome (6.89%) and that in the Te. nigroviridis genome (4.66%). In the repetitive DNA, 76% is retroelements which account for 6% of the sequenced D. holocanthus genome and belong to known families of transposable elements. More than half of retroelements were distributed within genes. In the non-homologous regions, repeat element proportion in D. holocanthus genome increased to 10.6% compared with T. rubripes and increased to 9.19% compared with Te. nigroviridis. A comparison of 10 well-defined orthologous genes showed that the average intron size (566 bp) in D. holocanthus genome is significantly longer than that in the smooth pufferfish genome (435 bp).

Conclusion
Compared with the smooth pufferfish, D. holocanthus has a low gene density and repeat elements rich genome. Genome size variation between D. holocanthus and the smooth pufferfish exhibits as length variation between homologous region and different accumulation of non-homologous sequences. The length difference of intron is consistent with the genome size variation between D. holocanthus and the smooth pufferfish. Different transposable element accumulation is responsible for genome size variation between D. holocanthus and the smooth pufferfish.
Characterization of the equine skeletal muscle transcriptome identifies novel functional responses to exercise training
Authors: McGivney Beatrice A , McGettigan Paul A , Browne John A , Evans Alexander CO , Fonseca Rita G , Loftus Brendan J , Lohan Amanda , MacHugh David E , Murphy Barbara A , Katz Lisa M , Hill Emmeline W 
Published: June 2010

AbstractBackgroundDigital gene expression profiling was used to characterize the assembly of genes expressed in equine skeletal muscle and to identify the subset of genes that were differentially expressed following a ten-month period of exercise training. The study cohort comprised seven Thoroughbred racehorses from a single training yard. Skeletal muscle biopsies were collected at rest from thegluteus mediusat two time points: T1- untrained, (9 ± 0.5 months old) and T2- trained (20 ± 0.7 months old).ResultsThe most abundant mRNA transcripts in the muscle transcriptome were those involved in muscle contraction, aerobic respiration and mitochondrial function. A previously unreported over-representation of genes related to RNA processing, the stress response and proteolysis was observed. Following training 92 tags were differentially expressed of which 74 were annotated. Sixteen genes showed increased expression, including the mitochondrial genesACADVL,MRPS21andSLC25A29encoded by the nuclear genome. Among the 58 genes with decreased expression,MSTN, a negative regulator of muscle growth, had the greatest decrease.Functional analysis of all expressed genes using FatiScan revealed an asymmetric distribution of 482 Gene Ontology (GO) groups and 18 KEGG pathways. Functional groups displaying highly significant (P< 0.0001) increased expression included mitochondrion, oxidative phosphorylation and fatty acid metabolism while functional groups with decreased expression were mainly associated with structural genes and included the sarcoplasm, laminin complex and cytoskeleton.ConclusionExercise training in Thoroughbred racehorses results in coordinate changes in the gene expression of functional groups of genes related to metabolism, oxidative phosphorylation and muscle structure.
The proline-rich peptide Bac7(1-35) reduces mortality from Salmonella typhimurium in a mouse model of infection
Authors: Benincasa Monica , Pelillo Chiara , Zorzet Sonia , Garrovo Chiara , Biffi Stefania , Gennaro Renato , Scocchi Marco 
Published: June 2010

Abstract

Background
Bac7 is a proline-rich peptide with a potent in vitro antimicrobial activity against Gram-negative bacteria. Here we investigated its activity in biological fluids and in vivo using a mouse model of S. typhimurium infection.

Results
The efficacy of the active 1-35 fragment of Bac7 was assayed in serum and plasma, and its stability in biological fluids analyzed by Western blot and mass spectrometry. The ability of the peptide to protect mice against Salmonella was assayed in a typhoid fever model of infection by determination of survival rates and bacterial load in liver and spleen of infected animals. In addition, the peptide's biodistribution was evaluated by using time-domain optical imaging. Bac7(1-35) retained a substantial in vivo activity showing a very low toxicity. The peptide increased significantly the number of survivors and the mean survival times of treated mice reducing the bacterial load in their organs despite its rapid clearance.

Conclusions
Our results provide a first indication for a potential development of Bac7-based drugs in the treatment of salmonellosis and, eventually, other Gram-negative infections. The in vivo activity for this peptide might be substantially enhanced by decreasing its excretion rate or modifying the treatment schedule.
Characterization of a diverse secretome generated by the mouse preimplantation embryo in vitro
Authors: Beardsley Amanda J , Li Yan , O'Neill Chris 
Published: June 2010

Abstract
This study investigates the suitability of surface-enhanced laser desorption and ionization time-of-flight (SELDI-TOF) and electrospray ionization (ESI) mass spectrometry for analysis of the proteins released by the mouse preimplantation embryo in vitro. SELDI-TOF analysis with CM10 or IMAC30 (but not Q10) protein chips detected a protein peak at m/z ~8570 released by both C57BL6 and hybrid embryos. No other peaks unique to the presence of the embryo were identified with this method. ESI mass spectrometry of tryptic digests of embryo-conditioned media identified a total of 20 proteins released during development from the zygote to blastocyst stage. Four proteins were expressed in at least 7 out of 8 cultures tested, one of these (lactate dehydrogenase B) was in all cultures. A further five proteins were in at least half of the cultures and 11 more proteins were in at least one culture. The expression of two of these proteins is essential for preimplantation embryo development (NLR family, pyrin domain containing 5 and peptidyl arginine deiminase, type VI). A further four proteins detected have roles in redox regulation of cells, and three others are capable of inducing post-translational modifications of proteins. This study shows the feasibility of ESI mass spectrometry for identifying the proteins secreted by the preimplantation embryo in vitro. This analysis identifies a range of targets that now require detailed functional analysis to assess whether their release by the embryo is an important property of early embryo development.
Semen-mediated enhancement of HIV infection is donor-dependent and correlates with the levels of SEVI
Authors: Kim Kyeong-Ae , Yolamanova Maral , Zirafi Onofrio , Roan Nadia R , Staendker Ludger , Forssmann Wolf-Georg , Burgener Adam , Dejucq-Rainsford Nathalie , Hahn Beatrice H , Shaw George M , Greene Warner C , Kirchhoff Frank , Münch Jan 
Published: June 2010

AbstractBackgroundHIV-1 is usually transmitted in the presence of semen. We have shown that semen boosts HIV-1 infection and contains fragments of prostatic acid phosphatase (PAP) forming amyloid aggregates termed SEVI (semen-derived enhancer of viral infection) that promote virion attachment to target cells. Despite its importance for the global spread of HIV-1, however, the effect of semen on virus infection is controversial.ResultsHere, we established methods allowing the meaningful analysis of semen by minimizing its cytotoxic effects and partly recapitulating the conditions encountered during sexual HIV-1 transmission. We show that semen rapidly and effectively enhances the infectivity of HIV-1, HIV-2, and SIV. This enhancement occurs independently of the viral genotype and coreceptor tropism as well as the virus producer and target cell type. Semen-mediated enhancement of HIV-1 infection was also observed under acidic pH conditions and in the presence of vaginal fluid. We further show that the potency of semen in boosting HIV-1 infection is donor dependent and correlates with the levels of SEVI.ConclusionsOur results show that semen strongly enhances the infectivity of HIV-1 and other primate lentiviruses and that SEVI contributes to this effect. Thus, SEVI may play an important role in the sexual transmission of HIV-1 and addition of SEVI inhibitors to microbicides may improve their efficacy.
LICAVAL: combination therapy in acute and maintenance treatment of bipolar disorder
Authors: Campos Rodolfo N , Costa Luis F , Bio Danielle S , Soeiro de Souza Márcio G , Garcia Carla RL , Demétrio Frederico N , Moreno Doris H , Moreno Ricardo A 
Published: June 2010

Abstract

Background
The challenge of Bipolar Disorder (BD) treatment is due to the complexity of the disease. Current guidelines represent an effort to help clinicians in their everyday practice but still have limitations, specially concerning to long term treatment. LICAVAL (efficacy and tolerability of the combination of

LI

thium and

CA

rbamazepine compared to lithium and

VAL

proic acid in the treatment of young bipolar patients) study aim to evaluate acute and maintenance phase of BD treatment with two combined drugs.

Methods
LICAVAL is a single site, parallel group, randomized, outcome assessor blinded trial. BD I patients according to the DSM-IV-TR, in depressive, manic,/hypomanic or mixed episode, aged 18 to 35 years are eligible. After the diagnostic assessments, the patients are allocated for one of the groups of treatment (lithium + valproic acid or lithium + carbamazepine). Patients will be followed up for 8 weeks in phase I (acute treatment), 6 months in phase II (continuation treatment) and 12 months in phase III (maintenance treatment). Outcome assessors are blind to the treatment. The main outcome is the evaluation of changes in mean scores on CGI-BP-M between baseline and endpoint at the end of each phase of the study.

Results
LICAVAL is currently in progress, with patients in phase I, II or III. It will extended until august 2012.

Conclusions
Trials comparing specific treatments efficacy in BD (head to head) can show relevant information in clinical practice. Long term treatment is an issue of great important and should be evaluated carefully in more studies as long as BD is a chronic disease.

Trial registration
ClinicalTrials.gov Identifier: NCT00976794
Senescent mouse cells fail to overtly regulate the HIRA histone chaperone and do not form robust Senescence Associated Heterochromatin Foci
Authors: Kennedy Alyssa L , McBryan Tony , Enders Greg H , Johnson F Brad , Zhang Rugang , Adams Peter D 
Published: June 2010

Abstract

Background
Cellular senescence is a permanent growth arrest that occurs in response to cellular stressors, such as telomere shortening or activation of oncogenes. Although the process of senescence growth arrest is somewhat conserved between mouse and human cells, there are some critical differences in the molecular pathways of senescence between these two species. Recent studies in human fibroblasts have defined a cell signaling pathway that is initiated by repression of a specific Wnt ligand, Wnt2. This, in turn, activates a histone chaperone HIRA, and culminates in formation of specialized punctate domains of facultative heterochromatin, called S enescence-A ssociated H eterochromatin F oci (SAHF), that are enriched in the histone variant, macroH2A. SAHF are thought to repress expression of proliferation-promoting genes, thereby contributing to senescence-associated proliferation arrest. We asked whether this Wnt2-HIRA-SAHF pathway is conserved in mouse fibroblasts.

Results
We show that mouse embryo fibroblasts (MEFs) and mouse skin fibroblasts, do not form robust punctate SAHF in response to an activated Ras oncogene or shortened telomeres. However, senescent MEFs do exhibit elevated levels of macroH2A staining throughout the nucleus as a whole. Consistent with their failure to fully activate the SAHF assembly pathway, the Wnt2-HIRA signaling axis is not overtly regulated between proliferating and senescent mouse cells.

Conclusions
In addition to the previously defined differences between mouse and human cells in the mechanisms and phenotypes associated with senescence, we conclude that senescent mouse and human fibroblasts also differ at the level of chromatin and the signaling pathways used to regulate chromatin. These differences between human and mouse senescence may contribute to the increased propensity of mouse fibroblasts (and perhaps other mouse cell types) to become immortalized and transformed, compared to human cells.
Digital gangrene associated with anticentromere antibodies: a case report
Authors: Bolster Lauren , Taylor-Gjevre Regina M , Nair Bindu , Gjevre John A 
Published: June 2010

Abstract

Introduction
Anticentromere antibodies have been associated with peripheral vascular occlusive disease, most frequently accompanied by sclerodactyly in the context of a connective tissue disorder. We report a case of digital gangrene with no other clinical associations except positive anticentromere antibodies.

Case presentation
Our patient, a 53-year-old Caucasian woman, non-smoker, presented with progressive pain and blackening of the distal right third finger over the preceding five weeks. No sclerodactyly was evident. She was anticentromere antibody positive at greater than 100 U/mL. Angiography revealed diffuse distal vasculopathy in both upper extremities. Other investigations were unremarkable.

Conclusions
It is rare for anticentromere antibody-associated digital necrosis to develop without concomitant sclerodactyly. However, this patient's case illustrates the need to consider an autoimmune contribution to the pathogenesis of digital ischemia even in the absence of a recognizable connective tissue disease.
The impact of HIV and high‐risk behaviours on the wives of married men who have sex with men and injection drug users: implications for HIV prevention
Authors: Solomon Sunil S , Mehta Shruti H , Latimore Amanda , Srikrishnan Aylur K , Celentano David D 
Published: June 2010

BackgroundHIV/AIDS in India disproportionately affects women, not by their own risks, but by those of their partners, generally their spouses. We address two marginalized populations at elevated risk of acquiring HIV: women who are married to men who also have sex with men (MSM) and wives of injection drug users (IDUs).MethodsWe used a combination of focus groups (qualitative) and structured surveys (quantitative) to identify the risks that high‐risk men pose to their low‐risk wives and/or sexual partners. Married MSM were identified using respondent‐driven recruitment in Tamil Nadu, India, and were interviewed by trainer assessors. A sample of wives of injection drug users in Chennai were recruited from men enrolled in a cohort study of the epidemiology of drug use among IDUs in Chennai, and completed a face‐to‐face survey. Focus groups were held with all groups of study participants, and the outcomes transcribed and analyzed for major themes on family, HIV and issues related to stigma, discrimination and disclosure.ResultsUsing mixed‐methods research, married MSM are shown to not disclose their sexual practices to their wives, whether due to internalized homophobia, fear of stigma and discrimination, personal embarrassment or changing sexual mores. Married MSM in India largely follow the prevailing norm of marriage to the opposite sex and having a child to satisfy social pressures. Male IDUs cannot hide their drug use as easily as married MSM, but they also avoid disclosure. The majority of their wives learn of their drug‐using behaviour only after they are married, making them generally helpless to protect themselves. Fear of poverty and negative influences on children were the major impacts associated with continuing drug use.ConclusionsWe propose a research and prevention agenda to address the HIV risks encountered by families of high‐risk men in the Indian and other low‐ and middle‐income country contexts.