bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydroxychloroquine drastically reduces immune activation in HIV-infected, antiretroviral therapy–treated immunologic nonresponders
Authors: Piconi Stefania , Parisotto Serena , Rizzardini Giuliano , Passerini Simone , Terzi Roberta , Argenteri Barbara , Meraviglia Paola , Capetti Amedeo , Biasin Mara , Trabattoni Daria , Clerici Mario 
Published: May 2011

Abstract
Despite optimal suppression of HIV replication, restoration of CD4+ T cells is not always achieved in antiretroviral therapy–treated individuals. Defective CD4 recovery in immunologic nonresponders is possibly associated with TLR-mediated immune activation driven by alterations of gut permeability. Hydroxychloroquine (HCQ) reduces endosomal TLR signaling; thus, we verified whether HCQ could dampen immune activation and be associated with an increase in CD4+ T cells. To this end, we enrolled in a prospective study 20 HIV-infected immunologic nonresponders (CD4 count < 200 cells/mL or CD4 increase < 5% in the last 12 months) who received 400 mg/day HCQ for 6 months. HCQ had a notable impact on immune activation as shown by significant modifications of the following parameters: (1) reduced plasma lipopolysaccharide; (2) decreased TLR4-expressing CD14+ cells, TLR4-mediated signal transduction, and mRNA synthesis; (3) reduced percentages of activated CD4+ (CD4+/Ki67+) and CD14+ (CD14+/CD69+) cells; (4) increased T-regulatory cells (Tregs), naive Tregs, and TLR4-expressing Tregs; (5) augmented plasmacytoid dendritic cells and reduced IFNα-secreting plasmacytoid dendritic cells; and (6) reduced IL-6 and TNFα production. HCQ-induced immune modulation was associated with increased percentages of circulating CD4+ T cells and was mostly retained 2 months after therapy interruption. HCQ reduces lipopolysaccharide/TLR-mediated immune activation; this compound could be a useful immunomodulant in HIV-infected patients. This study is registered at EutraCT as 2009-012499-28 with study number HLS01/2009-1-16-03-2009.
Genetic effects of polymorphisms in candidate genes and the QTL region on chicken age at first egg
Authors: Xu Haiping , Zeng Hua , Luo Chenglong , Zhang Dexiang , Wang Qian , Sun Liang , Yang Lishan , Zhou Min , Nie Qinghua , Zhang Xiquan 
Published: May 2011

Abstract

Background
The age at first egg (AFE), an important indicator for sexual maturation in female chickens, is controlled by polygenes. Based on our knowledge of reproductive physiology, 6 genes including gonadotrophin releasing hormone-I (GnRH-I), neuropeptide Y (NPY), dopamine D2 receptor (DRD2), vasoactive intestinal polypeptide (VIP), VIP receptor-1 (VIPR-1), and prolactin (PRL), were selected as candidates for influencing AFE. Additionally, the region between ADL0201 and MCW0241 of chromosome Z was chosen as the candidate QTL region according to some QTL databases. The objective of the present study was to investigate the effects of mutations in candidate genes and the QTL region on chicken AFE.

Results
Marker-trait association analysis of 8 mutations in those 6 genes in a Chinese native population found a highly significant association (P < 0.01) between G840327C of the GnRH-I gene with AFE, and it remained significant even with Bonferroni correction. Based on the results of the 2-tailed χ2 test, mutations T32742394C, T32742468C, G32742603A, and C33379782T in the candidate QTL region of chromosome Z were selected for marker-trait association analysis. The haplotypes of T32742394C and T32742468C were significantly associated (P < 0.05) with AFE. Bioinformatics analysis indicated that T32742394C and T32742468C were located in the intron region of the SH3-domain GRB2-like 2 (SH3GL2) gene, which appeared to be associated in the endocytosis and development of the oocyte.

Conclusion
This study found that G840327C of the GnRH-I gene and the haplotypes of T32742394C-T32742468C of the SH3GL2 gene were associated with the chicken AFE.
Comparative fecal metagenomics unveils unique functional capacity of the swine gut
Authors: Lamendella Regina , Santo Domingo Jorge W , Ghosh Shreya , Martinson John , Oerther Daniel B 
Published: May 2011

Abstract

Background
Uncovering the taxonomic composition and functional capacity within the swine gut microbial consortia is of great importance to animal physiology and health as well as to food and water safety due to the presence of human pathogens in pig feces. Nonetheless, limited information on the functional diversity of the swine gut microbiome is available.

Results
Analysis of 637, 722 pyrosequencing reads (130 megabases) generated from Yorkshire pig fecal DNA extracts was performed to help better understand the microbial diversity and largely unknown functional capacity of the swine gut microbiome. Swine fecal metagenomic sequences were annotated using both MG-RAST and JGI IMG/M-ER pipelines. Taxonomic analysis of metagenomic reads indicated that swine fecal microbiomes were dominated by Firmicutes and Bacteroidetes phyla. At a finer phylogenetic resolution, Prevotella spp. dominated the swine fecal metagenome, while some genes associated with Treponema and Anareovibrio species were found to be exclusively within the pig fecal metagenomic sequences analyzed. Functional analysis revealed that carbohydrate metabolism was the most abundant SEED subsystem, representing 13% of the swine metagenome. Genes associated with stress, virulence, cell wall and cell capsule were also abundant. Virulence factors associated with antibiotic resistance genes with highest sequence homology to genes in Bacteroidetes, Clostridia, and Methanosarcina were numerous within the gene families unique to the swine fecal metagenomes. Other abundant proteins unique to the distal swine gut shared high sequence homology to putative carbohydrate membrane transporters.

Conclusions
The results from this metagenomic survey demonstrated the presence of genes associated with resistance to antibiotics and carbohydrate metabolism suggesting that the swine gut microbiome may be shaped by husbandry practices.
Evolution in an oncogenic bacterial species with extreme genome plasticity: Helicobacter pyloriEast Asian genomes
Authors: Kawai Mikihiko , Furuta Yoshikazu , Yahara Koji , Tsuru Takeshi , Oshima Kenshiro , Handa Naofumi , Takahashi Noriko , Yoshida Masaru , Azuma Takeshi , Hattori Masahira , Uchiyama Ikuo , Kobayashi Ichizo 
Published: May 2011

Abstract

Background
The genome of Helicobacter pylori, an oncogenic bacterium in the human stomach, rapidly evolves and shows wide geographical divergence. The high incidence of stomach cancer in East Asia might be related to bacterial genotype. We used newly developed comparative methods to follow the evolution of East Asian H. pylori genomes using 20 complete genome sequences from Japanese, Korean, Amerind, European, and West African strains.

Results
A phylogenetic tree of concatenated well-defined core genes supported divergence of the East Asian lineage (hspEAsia; Japanese and Korean) from the European lineage ancestor, and then from the Amerind lineage ancestor. Phylogenetic profiling revealed a large difference in the repertoire of outer membrane proteins (including oipA, hopMN, babABC, sabAB and vacA-2) through gene loss, gain, and mutation. All known functions associated with molybdenum, a rare element essential to nearly all organisms that catalyzes two-electron-transfer oxidation-reduction reactions, appeared to be inactivated. Two pathways linking acetyl~CoA and acetate appeared intact in some Japanese strains. Phylogenetic analysis revealed greater divergence between the East Asian (hspEAsia) and the European (hpEurope) genomes in proteins in host interaction, specifically virulence factors (tipα), outer membrane proteins, and lipopolysaccharide synthesis (human Lewis antigen mimicry) enzymes. Divergence was also seen in proteins in electron transfer and translation fidelity (miaA, tilS), a DNA recombinase/exonuclease that recognizes genome identity (addA), and DNA/RNA hybrid nucleases (rnhAB). Positively selected amino acid changes between hspEAsia and hpEurope were mapped to products of cagA, vacA, homC (outer membrane protein), sotB (sugar transport), and a translation fidelity factor (miaA). Large divergence was seen in genes related to antibiotics: frxA (metronidazole resistance), def (peptide deformylase, drug target), and ftsA (actin-like, drug target).

Conclusions
These results demonstrate dramatic genome evolution within a species, especially in likely host interaction genes. The East Asian strains appear to differ greatly from the European strains in electron transfer and redox reactions. These findings also suggest a model of adaptive evolution through proteome diversification and selection through modulation of translational fidelity. The results define H. pylori East Asian lineages and provide essential information for understanding their pathogenesis and designing drugs and therapies that target them.
The impact of direct provision accommodation for asylum seekers on organisation and delivery of local primary care and social care services: A case study
Authors: Pieper Hans-Olaf , Clerkin Pauline , MacFarlane Anne 
Published: May 2011

Abstract

Background
Many western countries have policies of dispersal and direct provision accommodation (state-funded accommodation in an institutional centre) for asylum seekers. Most research focuses on its effect on the asylum seeking population. Little is known about the impact of direct provision accommodation on organisation and delivery of local primary care and social care services in the community. The aim of this research is to explore this issue.

Methods
In 2005 a direct provision accommodation centre was opened in a rural area in Ireland. A retrospective qualitative case study was designed comprising in-depth interviews with 37 relevant stakeholders. Thematic analysis following the principles of framework analysis was applied.

Results
There was lack of advance notification to primary care and social care professionals and the community about the new accommodation centre. This caused anxiety and stress among relevant stakeholders. There was insufficient time to plan and prepare appropriate primary care and social care for the residents, causing a significant strain on service delivery. There was lack of clarity about how primary care and social care needs of the incoming residents were to be addressed. Interdisciplinary support systems developed informally between healthcare professionals. This ensured that residents of the accommodation centre were appropriately cared for.

Conclusions
Direct provision accommodation impacts on the organisation and delivery of local primary care and social care services. There needs to be sufficient advance notification and inter-agency, inter-professional dialogue to manage this. Primary care and social care professionals working with asylum seekers should have access to training to enhance their skills for working in cross-cultural consultations.
Hypokalemic paralysis associated with cystic disease of the kidney: case report
Authors: Gamakaranage Champika SSSK , Rodrigo Chaturaka , Jayasinghe Saroj , Rajapakse Senaka 
Published: May 2011

Abstract

Background
Severe hypokalemia is known to cause muscle paralysis, and renal tubular acidosis is a recognized cause. Cystic disease of the kidney is associated with severe hypokalemia.

Case presentation
We report a 33-year-old male patient who presented with generalized limb weakness caused by severe hypokalemia due to renal tubular acidosis, who was found to have renal medullary cysts.

Conclusion
The association of cystic renal disease with hypokalemia, and the possible pathophysiological basis of the development of renal cysts in patients with severe hypokalemia, are discussed.
Keratin 23, a novel DPC4/Smad4 target gene which binds 14-3-3ε
Authors: Liffers Sven-T , Maghnouj Abdelouahid , Munding Johanna B , Jackstadt René , Herbrand Ulrike , Schulenborg Thomas , Marcus Katrin , Klein-Scory Susanne , Schmiegel Wolff , Schwarte-Waldhoff Irmgard , Meyer Helmut E , Stühler Kai , Hahn Stephan A 
Published: May 2011

Abstract

Background
Inactivating mutations of SMAD4 are frequent in metastatic colorectal carcinomas. In previous analyses, we were able to show that restoration of Smad4 expression in Smad4-deficient SW480 human colon carcinoma cells was adequate to suppress tumorigenicity and invasive potential, whereas in vitro cell growth was not affected. Using this cellular model system, we searched for new Smad4 targets comparing nuclear subproteomes derived from Smad4 re-expressing and Smad4 negative SW480 cells.

Methods
High resolution two-dimensional (2D) gel electrophoresis was applied to identify novel Smad4 targets in the nuclear subproteome of Smad4 re-expressing SW480 cells. The identified candidate protein Keratin 23 was further characterized by tandem affinity purification. Immunoprecipitation, subfractionation and immunolocalization studies in combination with RNAi were used to validate the Keratin 23-14-3-3ε interaction.

Results
We identified keratins 8 and 18, heat shock proteins 60 and 70, plectin 1, as well as 14-3-3ε and γ as novel proteins present in the KRT23-interacting complex. Co-immunoprecipitation and subfractionation analyses as well as immunolocalization studies in our Smad4-SW480 model cells provided further evidence that KRT23 associates with 14-3-3ε and that Smad4 dependent KRT23 up-regulation induces a shift of the 14-3-3ε protein from a nuclear to a cytoplasmic localization.

Conclusion
Based on our findings we propose a new regulatory circuitry involving Smad4 dependent up-regulation of KRT23 (directly or indirectly) which in turn modulates the interaction between KRT23 and 14-3-3ε leading to a cytoplasmic sequestration of 14-3-3ε. This cytoplasmic KRT23-14-3-3 interaction may alter the functional status of the well described 14-3-3 scaffold protein, known to regulate key cellular processes, such as signal transduction, cell cycle control, and apoptosis and may thus be a previously unappreciated facet of the Smad4 tumor suppressive circuitry.
Validity of the 32-item Hypomania Checklist (HCL-32) in a clinical sample with mood disorders in China
Authors: Yang Hai-chen , Yuan Cheng-mei , Liu Tie-bang , Li Ling-jiang , Peng Hong-jun , Liao Chun-ping , Rong Han , Fang Yi-ru , Angst Jules 
Published: May 2011

Abstract

Background
The 32-item Hypomania Checklist (HCL-32), a questionnaire for screening bipolar disorders, has been utilised in several countries, but it unclear if the Chinese version of the HCL-32 is valid.

Methods
Consecutive patients with bipolar disorders (BP, N = 300) and unipolar major depression (UP, N = 156) completed the Chinese version of the HCL-32. The subjects underwent a structured clinical interview for DSM-IV Axis-I disorders (SCID).

Results
The eigenvalues for the first three factors in the HCL-32 were calculated as 5.16 (active/elated), 2.72 (risk-taking) and 2.48 (irritable) using factor analysis. Cronbach's alpha for the HCL-32 was calculated to be 0.88. Positive responses to twenty-eight items were significantly more frequent by patients with BP than those with UP, and the other four items (7th, 21st, 25th and 32nd) showed no such trend. Fourteen was the optimal cut-off for discriminating between BP and UP. The HCL-32 distinguished between BP-II and UP, with 13 being the optimal cut-off. A cut-off of 13 yielded a sensitivity of 0.77 and a specificity of 0.62 between BP and UP.

Conclusions
This study demonstrated that the simplified Chinese version of HCL-32 was valid for patients with mood disorders. The optimal cut-off of 13 for distinguishing between BP-II and UP was valid and could be used to improve the sensitivity of screening BP-II patients when the HCL-32 is used in psychiatric settings in China.
Deficiency of mast cells in coronary artery endarterectomy of male patients with type 2 diabetes
Authors: Pleskovič Aleš , Vraspir-Porenta Olga , Zorc-Pleskovič Ruda , Petrovič Danijel , Zorc Metka , Milutinović Aleksandra 
Published: May 2011

Abstract

Background
Type 2 diabetes is an important risk factor for the development of coronary artery disease (CAD). Focal or diffuse inflammation is often present in the vessels of patients with CAD. Mast cells are frequently present in the plaques as well as in the inflammatory infiltrates in the atherosclerotic vessel wall. In the study we wanted to examine whether there are differences in the morphology, number and distribution of mast cells and in their ability to modify the atherosclerotic process in coronary arteries (CA) in the diabetic vs. the hypertensive population of patients with CAD.

Methods
Coronary artery endarterectomy specimens were obtained from patients with diabetes or hypertension as the only risk factor for CAD. The specimens were stained with haematoxylin-eosin and Sulphated Alcian Blue for mast cells and with immunofluorescent methods for fibrinogen-fibrin and IgG deposits in the vessel wall. Both morphological and stereological assessments were conducted for mast cells and mononuclear cell infiltrates.

Results
The histological analysis of the vessel wall of diabetic patients in comparison with hypertensive patients showed a damaged endothelial cells layer and deposits of fibrin-fibrinogen and IgG in the tunica intima and media. The stereological count revealed a diminished numerical density of mast cells and a significantly higher volume density of the mononuclear cells. Mast cells displayed cytoplasmic vacuolization, extracellular extrusion of granule and pyknotic nuclei.

Conclusion
This preliminary study suggests that the impaired mast cells might be the reason for more extensive inflammatory and immunologic atherosclerotic changes in the CA vessel wall of CAD patients with type 2 diabetes.

Trial registration
134/88;C3-0564-381-92
Inverse baseline expression pattern of the NEP/neuropeptides and NFκB/proteasome pathways in androgen-dependent and androgen-independent prostate cancer cells
Authors: Patrikidou Anna , Vlachostergios Panagiotis J , Voutsadakis Ioannis A , Hatzidaki Eleana , Valeri Rosalia-Maria , Destouni Chariklia , Apostolou Effie , Daliani Danai , Papandreou Christos N 
Published: May 2011

Abstract

Background
Castration-resistance in prostate cancer (PC) is a critical event hallmarking a switch to a more aggressive phenotype. Neuroendocrine differentiation and upregulation of NFκB transcriptional activity are two mechanisms that have been independently linked to this process.

Methods
We investigated these two pathways together using in vitro models of androgen-dependent (AD) and androgen-independent (AI) PC. We measured cellular levels, activity and surface expression of Neutral Endopeptidase (NEP), levels of secreted Endothelin-1 (ET-1), levels, sub-cellular localisation and DNA binding ability of NFκB, and proteasomal activity in human native PC cell lines (LnCaP and PC-3) modelling AD and AI states.

Results
At baseline, AD cells were found to have high NEP expression and activity and low secreted ET-1. In contrast, they exhibited a low-level activation of the NFκB pathway associated with comparatively low 20S proteasome activity. The AI cells showed the exact mirror image, namely increased proteasomal activity resulting in a canonical pathway-mediated NFκB activation, and minimal NEP activity with increased levels of secreted ET-1.

Conclusions
Our results seem to support evidence for divergent patterns of expression of the NFκB/proteasome pathway with relation to components of the NEP/neuropeptide axis in PC cells of different level of androgen dependence. NEP and ET-1 are inversely and directly related to an activated state of the NFκB/proteasome pathway, respectively. A combination therapy targeting both pathways may ultimately prove to be of benefit in clinical practice.
High prevalence of dhfr triple mutant and correlation with high rates of sulphadoxine-pyrimethamine treatment failures in vivo in Gabonese children
Authors: Mombo-Ngoma Ghyslain , Oyakhirome Sunny , Ord Rosalynn , Gabor Julian J , Greutélaers Katja C , Profanter Katharina , Greutélaers Benedikt , Kurth Florian , Lell Bertrand , Kun Jürgen FJ , Issifou Saadou , Roper Cally , Kremsner Peter G , Grobusch Martin P 
Published: May 2011

Abstract

Background
Drug resistance contributes to the global malaria burden. Plasmodium
falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) polymorphisms confer resistance to sulphadoxine-pyrimethamine (SP).

Methods
The study assessed the frequency of SP resistance-conferring polymorphisms in Plasmodium
falciparum-positive samples from two clinical studies in Lambaréné. Their role on treatment responses and transmission potential was studied in an efficacy open-label clinical trial with a 28-day follow-up in 29 children under five with uncomplicated malaria.

Results
SP was well tolerated by all subjects in vivo. Three subjects were excluded from per-protocol analysis. PCR-corrected, 12/26 (46%) achieved an adequate clinical and parasitological response, 13/26 (50%) were late parasitological failures, while 1/26 (4%) had an early treatment failure, resulting in early trial discontinuation. Of 106 isolates, 98 (92%) carried the triple mutant dhfr haplotype. Three point mutations were found in dhps in a variety of haplotypic configurations. The 437G + 540E double mutant allele was found for the first time in Gabon.

Conclusions
There is a high prevalence of dhfr triple mutant with some dhps point mutations in Gabon, in line with treatment failures observed, and molecular markers of SP resistance should be closely monitored.

Trial Registration
ClinicalTrials.gov: NCT00453856
Status of pesticide management in the practice of vector control: a global survey in countries at risk of malaria or other major vector-borne diseases
Authors: van den Berg Henk , Hii Jeffrey , Soares Agnes , Mnzava Abraham , Ameneshewa Birkinesh , Dash Aditya P , Ejov Mikhail , Tan Soo Hian , Matthews Graham , Yadav Rajpal S , Zaim Morteza 
Published: May 2011

Abstract

Background
It is critical that vector control pesticides are used for their acceptable purpose without causing adverse effects on health and the environment. This paper provides a global overview of the current status of pesticides management in the practice of vector control.

Methods
A questionnaire was distributed to WHO member states and completed either by the director of the vector-borne disease control programme or by the national manager for vector control. In all, 113 countries responded to the questionnaire (80% response rate), representing 94% of the total population of the countries targeted.

Results
Major gaps were evident in countries in pesticide procurement practices, training on vector control decision making, certification and quality control of pesticide application, monitoring of worker safety, public awareness programmes, and safe disposal of pesticide-related waste. Nevertheless, basic conditions of policy and coordination have been established in many countries through which the management of vector control pesticides could potentially be improved. Most countries responded that they have adopted relevant recommendations by the WHO.

Conclusions
Given the deficiencies identified in this first global survey on public health pesticide management and the recent rise in pesticide use for malaria control, the effectiveness and safety of pesticide use are being compromised. This highlights the urgent need for countries to strengthen their capacity on pesticide management and evidence-based decision making within the context of an integrated vector management approach.