bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between chronic glycosylated haemoglobin (HbA1c) level and macular volume in diabetes patients without macular oedema
Authors: Yeung Ling , Sun Chi‐Chin , Ku Wan‐Chen , Chuang Lan‐Hsin , Chen Chih‐Hung , Huang Bi‐Yu , Ting Ming‐Kuo , Yang Ko‐Jen 
Published: October 2009

Acta Ophthalmol. 2010: 88: 753–758Abstract.Purpose:  This study aimed to examine the correlation between glycosylated haemoglobin (HbA1c) level and macular volume in diabetes patients without diabetic macular oedema (DMO).Methods:  We carried out an observational, cross‐sectional study. Patients who had diabetes mellitus (DM) of ≥ 10 years duration without DMO were included. Only one eye of each patient was selected for analysis. Eyes with proliferative diabetic retinopathy were excluded. Central subfield thickness (CST), central subfield volume (CSV) and total macular volume (TMV) were measured by optical coherence tomography (OCT). Chronic HbA1c level was defined as the mean HbA1c value in the year prior to enrolment.Results:  We included 97 eyes from 97 patients (47 women, 50 men; mean age 62.2 years). They included eight type 1 and 89 type 2 DM patients. The mean duration of DM was 15.5 years. Forty‐two (43%) eyes had no diabetic retinopathy and 55 (57%) eyes had non‐proliferative diabetic retinopathy. In statistical analysis, CST (mean 188.80 ± 27.64 μm; r = 0.220, p = 0.030), CSV (mean 0.149 ± 0.021 mm3; r = 0.213, p = 0.036) and TMV (mean 6.497 ± 0.715 mm3; r = 0.299, p = 0.003) positively correlated with chronic HbA1c level (7.95 ± 1.29%). The linear regression model showed that chronic HbA1c level (standardized coefficient 0.253; p = 0.013) and age (standardized coefficient − 0.206; p = 0.040) were factors significantly related to TMV.Conclusions:  Chronic HbA1c level positively correlates with macular thickness and volume in patients with DM of ≥ 10 years duration without DMO. Our results suggest that subclinical macular volume and thickness changes may occur before DMO becomes clinically evident. Early tight glycaemic control prior to the onset of DMO may play an important role in preventing the deterioration of macular function by altering macular haemodynamics.
Peptide Microarray-Based Identification of
Mycobacterium tuberculosis
Epitope Binding to HLA-DRB1*0101, DRB1*1501, and DRB1*0401
Authors: Gaseitsiwe Simani , Valentini Davide , Mahdavifar Shahnaz , Reilly Marie , Ehrnst Anneka , Maeurer Markus 
Published: October 2009

ABSTRACT

A more effective vaccine against
Mycobacterium tuberculosis
is needed, and a number of
M. tuberculosis
vaccine candidates are currently in preclinical or clinical phase I and II studies. One of the strategies to select
M. tuberculosis
(protein) targets to elicit a CD8
+
or CD4
+
T-cell response is to gauge the binding of candidate peptides to major histocompatibility complex (MHC) class I or class II molecules, a prerequisite for successful peptide presentation and to expand antigen-specific T cells. We scanned 61 proteins from the
M. tuberculosis
proteome for potential MHC class II-presented epitopes that could serve as targets for CD4
+
T-cell responses. We constructed a peptide microarray consisting of 7,466 unique peptides derived from 61
M. tuberculosis
proteins. The peptides were 15-mers overlapping by 12 amino acids. Soluble recombinant DRB1*0101 (DR1), DRB1*1501 (DR2), and DRB1*0401 (DR4) monomers were used to gauge binding to individual peptide species. Out of 7,466 peptides, 1,282, 674, and 1,854 peptides formed stable complexes with HLA-DR1, -DR2, and -DR4, respectively. Five hundred forty-four peptides bound to all three MHC class II molecules, 609 bound to only two, and 756 bound to only a single MHC class II molecule. This allowed us to rank
M. tuberculosis
proteins by epitope density.
M. tuberculosis
proteins contained “hot spots,” i.e., regions with enriched MHC class II binding epitopes. Two hundred twenty-two peptides that formed MHC class II-peptide complexes had previously been described as exclusively recognized by IgG in sera from patients with active pulmonary tuberculosis, but not in sera from healthy individuals, suggesting that these peptides serve as B-cell and CD4
+
T-cell epitopes. This work helps to identify not only
M. tuberculosis
peptides with immunogenic potential, but also the most immunogenic proteins. This information is useful for vaccine design and the development of future tools to explore immune responses to
M. tuberculosis
.
Denmark14-230 Clone as an Increasing Cause of Pneumococcal Infection in Portugal within a Background of Diverse Serotype 19A Lineages
Authors: Aguiar Sandra I. , Pinto Francisco R. , Nunes Sónia , Serrano Isa , Melo-Cristino José , Sá-Leão Raquel , Ramirez Mário , de Lencastre Hermínia 
Published: October 2009

ABSTRACTPneumococci of serotype 19A are increasingly found to be the cause of infection in various geographic regions. We have characterized the serotype 19A isolates (n= 288) found among pneumococci responsible for infections (n= 1,925) and pneumococci recovered from asymptomatic carriers (n= 1,973) in Portugal between 2001 and 2006. We show that despite the existence of serotype 19A clones that have a greater potential to cause invasive disease or an enhanced colonization capacity, the lineage that is increasing as a cause of infection in Portugal is a multiresistant clone that is competent at both. The expanding Denmark14-230 clone found in Portugal is disseminated in other Mediterranean countries, where it is also increasingly responsible for invasive infections in both children and adults. The lineages driving the rise of serotype 19A infections in Asia and the United States (sequence type 320 [ST320] and ST199) are either absent or account for only a small proportion of isolates in Portugal. These data highlight the importance of locally circulating clones with the ability to compete in the nasopharyngeal niche in the emergence of the serotype 19A lineages which are an increasing cause of infection in various geographic regions.
Differential Downregulation of ACE2 by the Spike Proteins of Severe Acute Respiratory Syndrome Coronavirus and Human Coronavirus NL63
Authors: Glowacka Ilona , Bertram Stephanie , Herzog Petra , Pfefferle Susanne , Steffen Imke , Muench Marcus O. , Simmons Graham , Hofmann Heike , Kuri Thomas , Weber Friedemann , Eichler Jutta , Drosten Christian , Pöhlmann Stefan 
Published: October 2009

ABSTRACTThe human coronaviruses (CoVs) severe acute respiratory syndrome (SARS)-CoV and NL63 employ angiotensin-converting enzyme 2 (ACE2) for cell entry. It was shown that recombinant SARS-CoV spike protein (SARS-S) downregulates ACE2 expression and thereby promotes lung injury. Whether NL63-S exerts a similar activity is yet unknown. We found that recombinant SARS-S bound to ACE2 and induced ACE2 shedding with higher efficiency than NL63-S. Shedding most likely accounted for the previously observed ACE2 downregulation but was dispensable for viral replication. Finally, SARS-CoV but not NL63 replicated efficiently in ACE2-positive Vero cells and reduced ACE2 expression, indicating robust receptor interference in the context of SARS-CoV but not NL63 infection.
Some Generalizations of Fixed Point Theorems in Cone Metric Spaces
Authors: Olaleru J. O. 
Published: October 2009

AbstractWe generalize, extend, and improve some recent fixed point results in cone metric spaces including the results of H. Guang and Z. Xian (2007); P. Vetro (2007); M. Abbas and G. Jungck (2008); Sh. Rezapour and R. Hamlbarani (2008). In all our results, the normality assumption, which is a characteristic of most of the previous results, is dispensed. Consequently, the results generalize several fixed results in metric spaces including the results of G. E. Hardy and T. D. Rogers (1973), R. Kannan (1969), G. Jungck, S. Radenovic, S. Radojevic, and V. Rakocevic (2009), and all the references therein.
Experience of Caregiving in Schizophrenia: a Study From India
Authors: Aggarwal Munish , Avasthi Ajit , Kumar Suresh , Grover Sandeep 
Published: October 2009

Background: Many studies from India have evaluated the burden of schizophrenia on caregivers. Experience of caregiving, on the contrary, is a broader concept that takes into consideration both negative and positive consequences of the disorder and is influenced by factors like social support and coping of caregivers. Methodology: Fifty caregivers of patients with diagnosis of schizophrenia were assessed on Experience of Caregiving Inventory (ECI), Coping Checklist (CCL), Social Support Questionnaire (SSQ) and General Health Questionnaire-12 (GHQ-12). Patients were assessed on Positive and Negative Syndrome Scale (PANSS). Results: Maximum ECI score was seen in negative domains of handling the difficult behaviour followed by negative symptoms, loss and dependency. Significant positive correlation was seen between total positive ECI score and the level of education of patients and caregivers. Regression analysis showed that use of problem-focused coping, seeking social support as a coping strategy and education of caregivers explained 30.6% of the variance of ECI positive score. Conclusion: The study showed that education of caregivers, coping strategies used by the caregivers and available social support influence the final appraisal of caregiving.
Progressive Chondrocyte Death After Impact Injury Indicates a Need for Chondroprotective Therapy
Authors: Szczodry Michal , Coyle Christian H. , Kramer Scott J. , Smolinski Patrick , Chu Constance R. 
Published: October 2009

Background Impact injury to articular cartilage can lead to posttraumatic osteoarthritis. Hypotheses This study tests the hypotheses that (1) chondrocyte injury occurs after impact at energies insufficient to fracture the cartilage surface, and that (2) cartilage injury patterns vary with impact energy, time after injury, and cartilage thickness. Study Design Controlled laboratory study. Methods Fresh bovine osteochondral cores were randomly divided into 5 groups: (1) control, (2) 0.35 J, (3) 0.71 J, (4) 1.07 J, and (5) 1.43 J impact energies. Cores were subjected to computer-controlled impact loading and full-thickness sections were then prepared and incubated in Dulbecco’s Modified Eagle’s Medium/F12 at 37°C. Adjacent sections were harvested 1 and 4 days after impact for viability staining and fluorescent imaging. The area of dead and living chondrocytes was quantified using custom image analysis software and reported as a percentage of total cartilage area. Results The highest impact energy fractured the cartilage in all cores (1.43 J, n = 17). Seventy-three percent and 64% of the osteochondral cores remained intact after lower energy impacts of 0.71 J and 1.07 J, respectively. At lower energy levels, fractured cores were thinner ( P <.01) than those remaining intact. In cores remaining intact after impact injury, chondrocyte death increased with increasing impact energy ( P <.05) and with greater time after impact ( P <.05). A progressive increase in dead cells near the bone/cartilage interface and at the articular surface was observed. Conclusion These data showing progressive chondrocyte death after impact injury at energies insufficient to fracture the cartilage surface demonstrate a potential need for early chondroprotective therapy. Clinical Relevance These data show that efforts to reduce chondrocyte morbidity after joint injury may be a useful strategy to delay or prevent the onset of posttraumatic osteoarthritis.
A genome-wide association analysis of serum iron concentrations
Authors: Tanaka Toshiko , Roy Cindy N. , Yao Wenliang , Matteini Amy , Semba Richard D. , Arking Dan , Walston Jeremy D. , Fried Linda P. , Singleton Andrew , Guralnik Jack , Abecasis Gonçalo R. , Bandinelli Stefania , Longo Dan L. , Ferrucci Luigi 
Published: October 2009

Abstract
To investigate genetic variants that affect iron concentrations in persons not affected by overt genetic disorders of iron metabolism, a genome-wide association study was conducted in the InCHIANTI Study (N = 1206) and the Baltimore Longitudinal Study of Aging (N = 713). The top 2 single-nucleotide polymorphisms were examined for replication in the Women's Health and Aging Study (WHAS) I and II (N = 569). The single-nucleotide polymorphism most strongly associated with lower serum iron concentration was rs4820268 (P = 5.12 × 10−9), located in exon 13 of the transmembrane protease serine 6 (TMPRSS6) gene, an enzyme that promotes iron absorption and recycling by inhibiting hepcidin antimicrobial peptide transcription. The allele associated with lower iron concentrations was also associated with lower hemoglobin levels, smaller red cells, and more variability in red cell size (high red blood cell distribution width). Our results confirm the association of TMPRSS6 variants with iron level and provide further evidence of association with other anemia-related phenotypes.
A noncoding antisense RNA in tie-1 locus regulates tie-1 function in vivo
Authors: Li Keguo , Blum Yannick , Verma Anjali , Liu Zhong , Pramanik Kallal , Leigh Noah R. , Chun Chang Z. , Samant Ganesh V. , Zhao Baofeng , Garnaas Maija K. , Horswill Mark A. , Stanhope Stephen A. , North Paula E. , Miao Robert Q. , Wilkinson George A. , Affolter Markus , Ramchandran Ramani 
Published: October 2009

AbstractRecently, messenger RNAs in eukaryotes have shown to associate with antisense (AS) transcript partners that are often referred to as long noncoding RNAs (lncRNAs) whose function is largely unknown. Here, we have identified a natural AS transcript for tyrosine kinase containing immunoglobulin and epidermal growth factor homology domain-1 (tie-1), tie-1AS lncRNA in zebrafish, mouse, and humans. In embryonic zebrafish, tie-1AS lncRNA transcript is expressed temporally and spatially in vivo with its native target, the tie-1 coding transcript and in additional locations (ear and brain). The tie-1AS lncRNA selectively binds tie-1 mRNA in vivo and regulates tie-1 transcript levels, resulting in specific defects in endothelial cell contact junctions in vivo and in vitro. The ratio of tie-1 versus tie-1AS lncRNA is altered in human vascular anomaly samples. These results directly implicate noncoding RNA-mediated transcriptional regulation of gene expression as a fundamental control mechanism for physiologic processes, such as vascular development.
AIR: A batch-oriented web program package for construction of supermatrices ready for phylogenomic analyses
Authors: Kumar Surendra , Skjæveland Åsmund , Orr Russell JS , Enger Pål , Ruden Torgeir , Mevik Bjørn-Helge , Burki Fabien , Botnen Andreas , Shalchian-Tabrizi Kamran 
Published: October 2009

Abstract

Background
Large multigene sequence alignments have over recent years been increasingly employed for phylogenomic reconstruction of the eukaryote tree of life. Such supermatrices of sequence data are preferred over single gene alignments as they contain vastly more information about ancient sequence characteristics, and are thus more suitable for resolving deeply diverging relationships. However, as alignments are expanded, increasingly numbers of sites with misleading phylogenetic information are also added. Therefore, a major goal in phylogenomic analyses is to maximize the ratio of information to noise; this can be achieved by the reduction of fast evolving sites.

Results
Here we present a batch-oriented web-based program package, named AIR that allows 1) transformation of several single genes to one multigene alignment, 2) identification of evolutionary rates in multigene alignments and 3) removal of fast evolving sites. These three processes can be done with the programs AIR-A ppender, AIR-I dentifier, and AIR-R emover (AIR), which can be used independently or in a semi-automated pipeline. AIR produces user-friendly output files with filtered and non-filtered alignments where residues are colored according to their evolutionary rates. Other bioinformatics applications linked to the AIR package are available at the Bioportal http://www.bioportal.uio.no, University of Oslo; together these greatly improve the flexibility, efficiency and quality of phylogenomic analyses.

Conclusion
The AIR program package allows for efficient creation of multigene alignments and better assessment of evolutionary rates in sequence alignments. Removing fast evolving sites with the AIR programs has been employed in several recent phylogenomic analyses resulting in improved phylogenetic resolution and increased statistical support for branching patterns among the early diverging eukaryotes.
Staphylococcus aureus biofilm formation at the physiologic glucose concentration depends on the S. aureus lineage
Authors: Croes Sander , Deurenberg Ruud H , Boumans Marie-Louise L , Beisser Patrick S , Neef Cees , Stobberingh Ellen E 
Published: October 2009

Abstract

Background
Since bacteria embedded in biofilms are far more difficult to eradicate than planktonic infections, it would be useful to know whether certain Staphylococcus aureus lineages are especially involved in strong biofilm formation. For this reason, in vitro biofilm formation of 228 clinical S. aureus isolates of distinct clonal lineages was investigated.

Results
At 0.1% glucose, more than 60% of the S. aureus strains associated with multilocus sequence typing (MLST) clonal complex (CC)8 produced large amounts of biomass, compared to 0-7% for various other clonal lineages. Additionally, S. aureus bloodstream isolates associated with MLST CC8 and CC7 had similar biofilm forming capacities as their commensal counterparts. Furthermore, strong biofilm formation could not be attributed to a specific accessory gene regulator (agr) genotype, as suggested previously. The agr genotypes were strictly associated with the clonal lineages. Moreover, strong biofilm formation was not related to slime formation. Congo red agar (CRA) screening is therefore not useful as a qualitative screening method for biofilm formation.

Conclusion
The adherence to polystyrene surfaces under physiologic glucose concentration (0.1%) was dependent on the clonal lineage. Strains associated with MLST CC8 were markedly more often classified as strong biofilm former at glucose concentrations of 0%, 0.1% and 0.25%.
The present study reveals that the MLST CC8 associated genetic background was a predisposing factor for strong biofilm formation in vitro, under all tested glucose concentrations.
RAD51 paralogs promote homology-directed repair at diversifying immunoglobulin V regions
Authors: Ordinario Ellen C , Yabuki Munehisa , Handa Priya , Cummings W Jason , Maizels Nancy 
Published: October 2009

Abstract

Background
Gene conversion depends upon the same factors that carry out more general process of homologous recombination, including homologous gene targeting and recombinational repair. Among these are the RAD51 paralogs, conserved factors related to the key recombination factor, RAD51. In chicken and other fowl, gene conversion (templated mutation) diversifies immunoglobulin variable region sequences. This allows gene conversion and recombinational repair to be studied using the chicken DT40 B cell line, which carries out constitutive gene conversion and provides a robust and physiological model for homology-directed repair in vertebrate cells.

Results
We show that DT40 contains constitutive nuclear foci of the repair factors RAD51D and XRCC2, consistent with activated homologous recombination. Single-cell imaging of a DT40 derivative in which the rearranged and diversifying immunoglobulin λR light chain gene is tagged with polymerized lactose operator, DT40 PolyLacO-λR, showed that RAD51D and XRCC2 localize to the diversifying λR gene. Colocalizations correlate both functionally and physically with active immunoglobulin gene conversion. Ectopic expression of either RAD51D or XRCC2 accelerated the clonal rate of gene conversion, and conversion tracts were significantly longer in RAD51D than XRCC2 transfectants.

Conclusion
These results demonstrate direct functions of RAD51D and XRCC2 in immunoglobulin gene conversion, and also suggest that modulation of levels of repair factors may be a useful strategy to promote gene correction in other cell types.
Wnt pathway reprogramming during human embryonal carcinoma differentiation and potential for therapeutic targeting
Authors: Snow Grace E , Kasper Allison C , Busch Alexander M , Schwarz Elisabeth , Ewings Katherine E , Bee Thomas , Spinella Michael J , Dmitrovsky Ethan , Freemantle Sarah J 
Published: October 2009

Abstract

Background
Testicular germ cell tumors (TGCTs) are classified as seminonas or non-seminomas of which a major subset is embryonal carcinoma (EC) that can differentiate into diverse tissues. The pluripotent nature of human ECs resembles that of embryonic stem (ES) cells. Many Wnt signalling species are regulated during differentiation of TGCT-derived EC cells. This study comprehensively investigated expression profiles of Wnt signalling components regulated during induced differentiation of EC cells and explored the role of key components in maintaining pluripotency.

Methods
Human embryonal carcinoma cells were stably infected with a lentiviral construct carrying a canonical Wnt responsive reporter to assess Wnt signalling activity following induced differentiation. Cells were differentiated with all-trans retinoic acid (RA) or by targeted repression of pluripotency factor, POU5F1. A Wnt pathway real-time-PCR array was used to evaluate changes in gene expression as cells differentiated. Highlighted Wnt pathway genes were then specifically repressed using siRNA or stable shRNA and transfected EC cells were assessed for proliferation, differentiation status and levels of core pluripotency genes.

Results
Canonical Wnt signalling activity was low basally in undifferentiated EC cells, but substantially increased with induced differentiation. Wnt pathway gene expression levels were compared during induced differentiation and many components were altered including ligands (WNT2B), receptors (FZD5, FZD6, FZD10), secreted inhibitors (SFRP4, SFRP1), and other effectors of Wnt signalling (FRAT2, DAAM1, PITX2, Porcupine). Independent repression of FZD5, FZD7 and WNT5A using transient as well as stable methods of RNA interference (RNAi) inhibited cell growth of pluripotent NT2/D1 human EC cells, but did not appreciably induce differentiation or repress key pluripotency genes. Silencing of FZD7 gave the greatest growth suppression in all human EC cell lines tested including NT2/D1, NT2/D1-R1, Tera-1 and 833K cells.

Conclusion
During induced differentiation of human EC cells, the Wnt signalling pathway is reprogrammed and canonical Wnt signalling induced. Specific species regulating non-canonical Wnt signalling conferred growth inhibition when targeted for repression in these EC cells. Notably, FZD7 repression significantly inhibited growth of human EC cells and is a promising therapeutic target for TGCTs.