bluuebunny/crossref_metadata_2025_split huggingface dataset:
Th-1 polarization is regulated by dendritic-cell comparison of MHC class I and class II antigens
Authors: Decker William K. , Xing Dongxia , Li Sufang , Robinson Simon N. , Yang Hong , Steiner David , Komanduri Krishna V. , Shpall Elizabeth J. 
Published: January 2009

AbstractIn the control of T-helper type I (Th-1) polarization, dendritic cells (DCs) must interpret a complex array of stimuli, many of which are poorly understood. Here we demonstrate that Th-1 polarization is heavily influenced by DC-autonomous phenomena triggered by the loading of DCs with antigenically matched major histocompatibility complex (MHC) class I and class II determinants, that is, class I and II peptide epitopes exhibiting significant amino acid sequence overlap (such as would be physiologically present during infectious processes requiring Th-1 immunity for clearance). Data were derived from 13 independent antigenic models including whole-cell systems, single-protein systems, and 3 different pairs of overlapping class I and II binding epitopes. Once loaded with matched class I and II antigens, these “Th-1 DCs” exhibited differential cytokine secretion and surface marker expression, a distinct transcriptional signature, and acquired the ability to enhance generation of CD8+ T lymphocytes. Mechanistically, tRNA-synthetases were implicated as components of a putative sensor complex involved in the comparison of class I and II epitopes. These data provide rigorous conceptual explanations for the process of Th-1 polarization and the antigenic specificity of cognate T-cell help, enhance the understanding of Th-1 responses, and should contribute to the formulation of more effective vaccination strategies.
Expression of the leukemia oncogene Lmo2 is controlled by an array of tissue-specific elements dispersed over 100 kb and bound by Tal1/Lmo2, Ets, and Gata factors
Authors: Landry Josette-Renée , Bonadies Nicolas , Kinston Sarah , Knezevic Kathy , Wilson Nicola K. , Oram S. Helen , Janes Mary , Piltz Sandie , Hammett Michelle , Carter Jacinta , Hamilton Tina , Donaldson Ian J. , Lacaud Georges , Frampton Jonathan , Follows George , Kouskoff Valerie , Göttgens Berthold 
Published: January 2009

AbstractThe Lmo2 gene encodes a transcriptional cofactor critical for the development of hematopoietic stem cells. Ectopic LMO2 expression causes leukemia in T-cell acute lymphoblastic leukemia (T-ALL) patients and severe combined immunodeficiency patients undergoing retroviral gene therapy. Tightly controlled Lmo2 expression is therefore essential, yet no comprehensive analysis of Lmo2 regulation has been published so far. By comparative genomics, we identified 17 highly conserved noncoding elements, 9 of which revealed specific acetylation marks in chromatin-immunoprecipitation and microarray (ChIP-chip) assays performed across 250 kb of the Lmo2 locus in 11 cell types covering different stages of hematopoietic differentiation. All candidate regulatory regions were tested in transgenic mice. An extended LMO2 proximal promoter fragment displayed strong endothelial activity, while the distal promoter showed weak forebrain activity. Eight of the 15 distal candidate elements functioned as enhancers, which together recapitulated the full expression pattern of Lmo2, directing expression to endothelium, hematopoietic cells, tail, and forebrain. Interestingly, distinct combinations of specific distal regulatory elements were required to extend endothelial activity of the LMO2 promoter to yolk sac or fetal liver hematopoietic cells. Finally, Sfpi1/Pu.1, Fli1, Gata2, Tal1/Scl, and Lmo2 were shown to bind to and transactivate Lmo2 hematopoietic enhancers, thus identifying key upstream regulators and positioning Lmo2 within hematopoietic regulatory networks.
Regulation of macrophage function in tumors: the multifaceted role of NF-κB
Authors: Hagemann Thorsten , Biswas Subhra K. , Lawrence Toby , Sica Antonio , Lewis Claire E. 
Published: January 2009

AbstractThe pivotal role of tumor-associated macrophages (TAMs) in tumor progression is now well established. TAMs have been shown to influence multiple steps in tumor development including the growth, survival, invasion, and metastasis of tumor cells as well as angiogenesis and lymphangiogenesis in tumors. The molecular circuits that polarize TAMs toward such a protumoral phenotype are now the focus of intense investigation. The transcription factor, nuclear factor–κB (NF-κB), is a master regulator of many cellular processes and been shown to regulate various pathways that impact on the function of TAMs. Much evidence for this has come from the use of elegant transgenic murine tumor models in which modification of single components of the NF-κB signaling pathway has been shown to regulate the pro-tumor repertoire of TAMs. Here, we outline this evidence and attempt to reconcile the various views that have emerged recently over the exact role of NF-κB in this phenomenon.
Assessment of codivergence of Mastreviruses with their plant hosts
Authors: Wu Beilei , Melcher Ulrich , Guo Xingyi , Wang Xifeng , Fan Longjiang , Zhou Guanghe 
Published: January 2009

Abstract

Background
Viruses that have spent most of their evolutionary time associated with a single host lineage should have sequences that reflect codivergence of virus and host. Several examples for RNA viruses of host-virus tree congruence are being challenged. DNA viruses, such as mastreviruses, are more likely than RNA viruses to have maintained a record of host lineage association.

Results
The full genomes of 28 isolates of Wheat dwarf virus (WDV), a member of the Mastrevirus genus, from different regions of China were sequenced. The analysis of these 28 entire genomes and 18 entire genome sequences of cereal mastreviruses from other countries support the designation of wheat, barley and oat mastrevirus isolates as separate species. They revealed that relative divergence times for the viruses WDV, Barley dwarf virus (BDV), Oat dwarf virus (ODV) and Maize streak virus (MSV) are proportional to divergence times of their hosts, suggesting codivergence. Considerable diversity among Chinese isolates was found and was concentrated in hot spots in the Rep A, SIR, LIR, and intron regions in WDV genomes. Two probable recombination events were detected in Chinese WDV isolates. Analysis including further Mastrevirus genomes concentrated on coding regions to avoid difficulties due to recombination and hyperdiversity. The analysis demonstrated congruence of trees in two branches of the genus, but not in the third. Assuming codivergence, an evolutionary rate of 10-8 substitutions per site per year was calculated. The low rate implies stronger constraints against change than are obtained by other methods of estimating the rate.

Conclusion
We report tests of the hypothesis that mastreviruses have codiverged with their monocotyledonous hosts over 50 million years of evolution. The tests support the hypothesis for WDV, BDV and ODV, but not for MSV and other African streak viruses.
Genome and gene alterations by insertions and deletions in the evolution of human and chimpanzee chromosome 22
Authors: Volfovsky Natalia , Oleksyk Taras K , Cruz Kristine C , Truelove Ann L , Stephens Robert M , Smith Michael W 
Published: January 2009

Abstract

Background
Understanding structure and function of human genome requires knowledge of genomes of our closest living relatives, the primates. Nucleotide insertions and deletions (indels) play a significant role in differentiation that underlies phenotypic differences between humans and chimpanzees. In this study, we evaluated distribution, evolutionary history, and function of indels found by comparing syntenic regions of the human and chimpanzee genomes.

Results
Specifically, we identified 6,279 indels of 10 bp or greater in a ~33 Mb alignment between human and chimpanzee chromosome 22. After the exclusion of those in repetitive DNA, 1,429 or 23% of indels still remained. This group was characterized according to the local or genome-wide repetitive nature, size, location relative to genes, and other genomic features. We defined three major classes of these indels, using local structure analysis: (i) those indels found uniquely without additional copies of indel sequence in the surrounding (10 Kb) region, (ii) those with at least one exact copy found nearby, and (iii) those with similar but not identical copies found locally. Among these classes, we encountered a high number of exactly repeated indel sequences, most likely due to recent duplications. Many of these indels (683 of 1,429) were in proximity of known human genes. Coding sequences and splice sites contained significantly fewer of these indels than expected from random expectations, suggesting that selection is a factor in limiting their persistence. A subset of indels from coding regions was experimentally validated and their impacts were predicted based on direct sequencing in several human populations as well as chimpanzees, bonobos, gorillas, and two subspecies of orangutans.

Conclusion
Our analysis demonstrates that while indels are distributed essentially randomly in intergenic and intronic genomic regions, they are significantly under-represented in coding sequences. There are substantial differences in representation of indel classes among genomic elements, most likely caused by differences in their evolutionary histories. Using local sequence context, we predicted origins and phylogenetic relationships of gene-impacting indels in primate species. These results suggest that genome plasticity is a major force behind speciation events separating the great ape lineages.
Low frequency of CD4+CD25+ Treg in SLE patients: a heritable trait associated with CTLA4 and TGFβ gene variants
Authors: Barreto Marta , Ferreira Ricardo C , Lourenço Lara , Moraes-Fontes Maria F , Santos Eugénia , Alves Miguel , Carvalho Cláudia , Martins Berta , Andreia Rita , Viana João F , Vasconcelos Carlos , Mota-Vieira Luísa , Ferreira Carlos , Demengeot Jocelyne , Vicente Astrid M 
Published: January 2009

AbstractBackgroundCD4+CD25+regulatory T cells play an essential role in maintaining immune homeostasis and preventing autoimmunity. Therefore, defects in Treg development, maintenance or function have been associated with several human autoimmune diseases including Systemic Lupus Erythematosus (SLE), a systemic autoimmune disease characterized by loss of tolerance to nuclear components and significantly more frequent in females.ResultsTo investigate the involvement of Treg in SLE pathogenesis, we determined the frequency of CD4+CD25+CD45RO+T cells, which encompass the majority of Treg activity, in the PBMC of 148 SLE patients (76 patients were part of 54 families), 166 relatives and 117 controls. SLE patients and their relatives were recruited in several Portuguese hospitals and through the Portuguese Lupus Association. Control individuals were blood donors recruited from several regional blood donor centers. Treg frequency was significantly lower in SLE patients than healthy controls (z = -6.161,P< 0.00001) and intermediate in the relatives' group. Remarkably, this T cell subset was also lower in females, most strikingly in the control population (z = 4.121,P< 0.001). We further ascertained that the decreased frequency of Treg in SLE patients resulted from the specific reduction ofbona fideFOXP3+CD4+CD25+Treg. Treg frequency was negatively correlated with SLE activity index (SLEDAI) and titers of serum anti-dsDNA antibodies. Both Treg frequency and disease activity were modulated by IVIg treatment in a documented SLE case. The segregation of Treg frequency within the SLE families was indicative of a genetic trait. Candidate gene analysis revealed that specific variants ofCTLA4andTGFβwere associated with the decreased frequency of Treg in PBMC, whileFOXP3gene variants were associated with affection status, but not with Treg frequency.ConclusionSLE patients have impaired Treg production or maintenance, a trait strongly associated with SLE disease activity and autoantibody titers, and possibly resulting from the inability to convert FOXP3+CD25-into FOXP3+CD25+T cells. Treg frequency is highly heritable within SLE families, with specific variants of theCTLA4andTGFβgenes contributing to this trait, whileFOXP3contributes to SLE through mechanisms not involving a modulation of Treg frequency. These findings establish that the genetic components in SLE pathogenesis include genes related to Treg generation or maintenance.
Ultrastructure and molecular phylogeny of Calkinsia aureus: cellular identity of a novel clade of deep-sea euglenozoans with epibiotic bacteria
Authors: Yubuki Naoji , Edgcomb Virginia P , Bernhard Joan M , Leander Brian S 
Published: January 2009

AbstractBackgroundThe Euglenozoa is a large group of eukaryotic flagellates with diverse modes of nutrition. The group consists of three main subclades – euglenids, kinetoplastids and diplonemids – that have been confirmed with both molecular phylogenetic analyses and a combination of shared ultrastructural characteristics. Several poorly understood lineages of putative euglenozoans live in anoxic environments, such asCalkinsia aureus, and have yet to be characterized at the molecular and ultrastructural levels. Improved understanding of these lineages is expected to shed considerable light onto the ultrastructure of prokaryote-eukaryote symbioses and the associated cellular innovations found within the Euglenozoa and beyond.ResultsWe collectedCalkinsia aureusfrom core samples taken from the low-oxygen seafloor of the Santa Barbara Basin (580 – 592 m depth), California. These biflagellates were distinctively orange in color and covered with a dense array of elongated epibiotic bacteria. Serial TEM sections through individually prepared cells demonstrated thatC. aureusshares derived ultrastructural features with other members of the Euglenozoa (e.g. the same paraxonemal rods, microtubular root system and extrusomes). However,C. aureusalso possessed several novel ultrastructural systems, such as modified mitochondria (i.e. hydrogenosome-like), an "extrusomal pocket", a highly organized extracellular matrix beneath epibiotic bacteria and a complex flagellar transition zone. Molecular phylogenies inferred from SSU rDNA sequences demonstrated thatC. aureusgrouped strongly within the Euglenozoa and with several environmental sequences taken from low-oxygen sediments in various locations around the world.ConclusionCalkinsia aureuspossesses all of the synapomorphies for the Euglenozoa, but lacks traits that are specific to any of the three previously recognized euglenozoan subgroups. Molecular phylogenetic analyses ofC. aureusdemonstrate that this lineage is a member of a novel euglenozoan subclade consisting of uncharacterized cells living in low-oxygen environments. Our ultrastructural description ofC. aureusestablishes the cellular identity of a fourth group of euglenozoans, referred to as the "Symbiontida".
The tep1 gene of Sinorhizobium meliloti coding for a putative transmembrane efflux protein and N-acetyl glucosamine affect nod gene expression and nodulation of alfalfa plants
Authors: van Dillewijn Pieter , Sanjuán Juan , Olivares José , Soto María José 
Published: January 2009

Abstract

Background
Soil bacteria collectively known as Rhizobium, characterized by their ability to establish beneficial symbiosis with legumes, share several common characteristics with pathogenic bacteria when infecting the host plant. Recently, it was demonstrated that a fadD mutant of Sinorhizobium meliloti is altered in the control of swarming, a type of co-ordinated movement previously associated with pathogenicity, and is also impaired in nodulation efficiency on alfalfa roots. In the phytopathogen Xanthomonas campestris, a fadD homolog (rpfB) forms part of a cluster of genes involved in the r egulation of p athogenicity f actors. In this work, we have investigated the role in swarming and symbiosis of SMc02161, a S. meliloti fadD-linked gene.

Results
The SMc02161 locus in S. meliloti shows similarities with members of the Major Facilitator Superfamily (MFS) of transporters. A S. meliloti null-mutant shows increased sensitivity to chloramphenicol. This indication led us to rename the locus tep1 for t ransmembrane e fflux p rotein. The lack of tep1 does not affect the appearance of swarming motility. Interestingly, nodule formation efficiency on alfalfa plants is improved in the tep1 mutant during the first days of the interaction though nod gene expression is lower than in the wild type strain. Curiously, a nodC mutation or the addition of N-acetyl glucosamine to the wild type strain lead to similar reductions in nod gene expression as in the tep1 mutant. Moreover, aminosugar precursors of Nod factors inhibit nodulation.

Conclusion

tep1 putatively encodes a transmembrane protein which can confer chloramphenicol resistance in S. meliloti by expelling the antibiotic outside the bacteria. The improved nodulation of alfalfa but reduced nod gene expression observed in the tep1 mutant suggests that Tep1 transports compounds which influence nodulation. In contrast to Bradyrhizobium japonicum, we show that in S. meliloti there is no feedback regulation of nodulation genes. Moreover, the Nod factor precursor, N-acetyl glucosamine reduces nod gene expression and nodulation efficiency when present at millimolar concentrations. A role for Tep1 in the efflux of Nod factor precursors could explain the phenotypes associated with tep1 inactivation.
Improper excess light energy dissipation in Arabidopsis results in a metabolic reprogramming
Authors: Frenkel Martin , Külheim Carsten , Jänkänpää Hanna Johansson , Skogström Oskar , Dall'Osto Luca , Ågren Jon , Bassi Roberto , Moritz Thomas , Moen Jon , Jansson Stefan 
Published: January 2009

Abstract

Background
Plant performance is affected by the level of expression of PsbS, a key photoprotective protein involved in the process of feedback de-excitation (FDE), or the qE component of non-photochemical quenching, NPQ.

Results
In studies presented here, under constant laboratory conditions the metabolite profiles of leaves of wild-type Arabidopsis thaliana and plants lacking or overexpressing PsbS were very similar, but under natural conditions their differences in levels of PsbS expression were associated with major changes in metabolite profiles. Some carbohydrates and amino acids differed ten-fold in abundance between PsbS-lacking mutants and over-expressers, with wild-type plants having intermediate amounts, showing that a metabolic shift had occurred. The transcriptomes of the genotypes also varied under field conditions, and the genes induced in plants lacking PsbS were similar to those reportedly induced in plants exposed to ozone stress or treated with methyl jasmonate (MeJA). Genes involved in the biosynthesis of JA were up-regulated, and enzymes involved in this pathway accumulated. JA levels in the undamaged leaves of field-grown plants did not differ between wild-type and PsbS-lacking mutants, but they were higher in the mutants when they were exposed to herbivory.

Conclusion
These findings suggest that lack of FDE results in increased photooxidative stress in the chloroplasts of Arabidopsis plants grown in the field, which elicits a response at the transcriptome level, causing a redirection of metabolism from growth towards defence that resembles a MeJA/JA response.
Prevalence of tuberculosis drug resistance in 10 provinces of China
Authors: He Guang Xue , Zhao Yan Lin , Jiang Guang Lu , Liu Yu Hong , Xia Hui , Wang Sheng Fen , Wang Li Xia , Borgdorff Martien W , van der Werf Marieke J , van den Hof Susan 
Published: January 2009

Abstract

Background
The emergence of drug-resistant tuberculosis (TB) hampers TB control. Ten provinces in China performed drug resistance surveys among tuberculosis (TB) patients in 1996–2004 to assess levels of drug resistance.

Methods
Provincial drug resistance surveys included all isolates from newly diagnosed, smear-positive TB patients. Drug susceptibility testing (DST) against isoniazid, rifampicin, streptomycin and ethambutol was carried out in the provincial laboratories. For purposes of quality assurance, a random sample (11.6%) was re-tested by the national reference laboratory (NRL).

Results
Of 14,059 patients tested 11,052 (79%) were new TB cases. The weighted mean prevalence of multi-drug resistant tuberculosis (MDR-TB) among all cases was 9.3% (range 2.2%–10.4%); 5.4% (range 2.1% – 10.4%) among new cases and 25.6% (range 11.7%–36.9%) among previously treated cases. Adjusting the drug resistance proportions using the re-testing results did not change the estimated national mean prevalence significantly. However, in some individual provinces the estimated resistance proportions were greatly influenced, especially among re-treatment patients.

Conclusion
MDR-TB levels varied greatly between provinces in China, but on average were high compared to the global estimated average of 4.8%. This study shows the importance of quality-assured laboratory performance. Programmatic management of drug-resistant TB, including high quality DST for patients at high risk of resistance and treatment with second-line drugs, should become the standard, especially in high MDR-TB settings.
A randomised controlled trial evaluating the effect of an individual auditory cueing device on freezing and gait speed in people with Parkinson's disease
Authors: Ledger Sean , Galvin Rose , Lynch Deirdre , Stokes Emma K 
Published: January 2009

Abstract

Background
Parkinson's disease is a progressive neurological disorder resulting from a degeneration of dopamine producing cells in the substantia nigra. Clinical symptoms typically affect gait pattern and motor performance. Evidence suggests that the use of individual auditory cueing devices may be used effectively for the management of gait and freezing in people with Parkinson's disease. The primary aim of the randomised controlled trial is to evaluate the effect of an individual auditory cueing device on freezing and gait speed in people with Parkinson's disease.

Methods
A prospective multi-centre randomised cross over design trial will be conducted. Forty-seven subjects will be randomised into either Group A or Group B, each with a control and intervention phase. Baseline measurements will be recorded using the Freezing of Gait Questionnaire as the primary outcome measure and 3 secondary outcome measures, the 10 m Walk Test, Timed "Up & Go" Test and the Modified Falls Efficacy Scale. Assessments are taken 3-times over a 3-week period. A follow-up assessment will be completed after three months. A secondary aim of the study is to evaluate the impact of such a device on the quality of life of people with Parkinson's disease using a qualitative methodology.

Conclusion
The Apple iPod-Shuffle™ and similar devices provide a cost effective and an innovative platform for integration of individual auditory cueing devices into clinical, social and home environments and are shown to have immediate effect on gait, with improvements in walking speed, stride length and freezing. It is evident that individual auditory cueing devices are of benefit to people with Parkinson's disease and the aim of this randomised controlled trial is to maximise the benefits by allowing the individual to use devices in both a clinical and social setting, with minimal disruption to their daily routine.

Trial registration
The protocol for this study is registered with the US NIH Clinical Trials Registry (NCT00727467).