bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired lung compliance andDL,CObut no restrictive ventilatory defect in sarcoidosis
Authors: Boros P.W. , Enright P.L. , Quanjer P.H. , Borsboom G.J.J.M. , Wesolowski S.P. , Hyatt R.E. 
Published: April 2010

Sarcoidosis is a systemic granulomatous disease with predominant manifestation in the lungs, often presenting as interstitial lung disease. Pulmonary function abnormalities in sarcoidosis include restriction of lung volumes, reduction in diffusing capacity of the lung for carbon monoxide (DL,CO), reduced static lung compliance (CL,s) and airway obstruction. The aim of the present study was to assess various lung function indices, includingCL,sandDL,CO, as markers of functional abnormality in sarcoidosis patients.Results from 830 consecutive patients referred for lung function tests with a diagnosis of sarcoidosis (223 in stage I, 486 in stage II and 121 in stage III) were retreospectively analysed. The mean±sdage of the patients was 40±11 yrs; 18% were active smokers and 24% were former smokers.Normal total lung capacity was found in 772 (93%) patients. Of these cases, 24.5% had a lowCL,sand 21.5% had a lowDL,CO. At least one abnormality was observed in 39.3% of these patients, whereas, in restrictive patients, this figure was 88%. Airway obstruction was present in 11.7% of cases.Lung volumes usually remain within the normal range and measurement of eitherCL,sorDL,COoften reveal impaired lung function in sarcoidosis patients, even when their lung volumes are still in the normal range; these two measurements provide complementary information.
Optimization algorithms for functional deimmunization of therapeutic proteins
Authors: Parker Andrew S , Zheng Wei , Griswold Karl E , Bailey-Kellogg Chris 
Published: April 2010

AbstractBackgroundTo develop protein therapeutics from exogenous sources, it is necessary to mitigate the risks of eliciting an anti-biotherapeutic immune response. A key aspect of the response is the recognition and surface display by antigen-presenting cells of epitopes, short peptide fragments derived from the foreign protein. Thus, developing minimal-epitope variants represents a powerful approach to deimmunizing protein therapeutics. Critically, mutations selected to reduce immunogenicity must not interfere with the protein's therapeutic activity.ResultsThis paper develops methods to improve the likelihood of simultaneously reducing the anti-biotherapeutic immune response while maintaining therapeutic activity. A dynamic programming approach identifies optimal and near-optimal sets of conservative point mutations to minimize the occurrence of predicted T-cell epitopes in a target protein. In contrast with existing methods, those described here integrate analysis of immunogenicity and stability/activity, are broadly applicable to any protein class, guarantee global optimality, and provide sufficient flexibility for users to limit the total number of mutations and target MHC alleles of interest. The input is simply the primary amino acid sequence of the therapeutic candidate, although crystal structures and protein family sequence alignments may also be input when available. The output is a scored list of sets of point mutations predicted to reduce the protein's immunogenicity while maintaining structure and function. We demonstrate the effectiveness of our approach in a number of case study applications, showing that, in general, our best variants are predicted to be better than those produced by previous deimmunization efforts in terms of either immunogenicity or stability, or both factors.ConclusionsBy developing global optimization algorithms leveraging well-established immunogenicity and stability prediction techniques, we provide the protein engineer with a mechanism for exploring the favorable sequence space near a targeted protein therapeutic. Our mechanism not only helps identify designs more likely to be effective, but also provides insights into the interrelated implications of design choices.
Relative roles of the different Pax6 domains for pancreatic alpha cell development
Authors: Dames Petra , Puff Ramona , Weise Michaela , Parhofer Klaus G , Göke Burkhard , Götz Magdalena , Graw Jochen , Favor Jack , Lechner Andreas 
Published: April 2010

Abstract

Background
The transcription factor Pax6 functions in the specification and maintenance of the differentiated cell lineages in the endocrine pancreas. It has two DNA binding domains, the paired domain and the homeodomain, in addition to a C-terminal transactivation domain. The phenotype of Pax6-/- knockout mice suggests non-redundant functions of the transcription factor in the development of glucagon-expressing α-cells as this cell type is absent in the mutants. We ask the question of how the differentiation of pancreatic endocrine cells, in particular that of α-cells, is affected by selective inactivation of either one of the three major domains of Pax6.

Results
The Pax6Aey18 mutant mouse line, in which the paired domain is inactivated, showed a phenotype similar to that of Pax6-/- knockout mice with a near complete absence of glucagon-positive α-cells (0-4 cells/section; ≤1% of wt), reduced β-cell area (74% of wt) and disorganized islets. The proportion of ghrelin-positive ε-cells was expanded. In Pax6Sey-Neu mutants, which lack the transactivation domain, α-and β-cells where reduced to 25 and 40% of wt, respectively. We also studied two mouse lines with mutations in the homeodomain, Pax64Neu and Pax6132-14Neu. Neighboring amino acids are affected in the two lines and both point mutations abolish DNA binding of the classical P3 homeodomain target sequence. The pancreatic phenotype of the two mutants however was divergent. While Pax64Neu homozygotes showed a reduction of α- and β-cells to 59 and 61%, respectively, pancreatic endocrine development was unaltered in the Pax6132-14Neu mutant strain.

Conclusions
We show that inactivation of the Pax6 paired domain leads to a more severe phenotype with regards to the differentiation of pancreatic α-cells than the loss of the transactivation domain. The analysis of two different homeodomain mutants suggests that the binding of Pax6 to P3 homeodomain consensus sequences is not required for α-cell development. It rather seems that the homeodomain has a modulating role in Pax6 function, possibly by facilitating a PH0-like binding confirmation on paired domain target genes like proglucagon. This function is differentially affected by the two homeodomain mutations analyzed in this study.
Identification of copy number variations and common deletion polymorphisms in cattle
Authors: Bae Joon Seol , Cheong Hyun Sub , Kim Lyoung Hyo , NamGung Suk , Park Tae Joon , Chun Ji-Yong , Kim Jason Yongha , Pasaje Charisse Flerida A , Lee Jin Sol , Shin Hyoung Doo 
Published: April 2010

Abstract

Background
Recently, the discovery of copy number variation (CNV) led researchers to think that there are more variations of genomic DNA than initially believed. Moreover, a certain CNV region has been found to be associated with the onset of diseases. Therefore, CNV is now known as an important genomic variation in biological mechanisms. However, most CNV studies have only involved the human genome. The study of CNV involving other animals, including cattle, is severely lacking.

Results
In our study of cattle, we used Illumina BovineSNP50 BeadChip (54,001 markers) to obtain each marker's signal intensity (Log R ratio) and allelic intensity (B allele frequency), which led to our discovery of 855 bovine CNVs from 265 cows. For these animals, the average number of CNVs was 3.2, average size was 149.8 kb, and median size was 171.5 kb. Taking into consideration some overlapping regions among the identified bovine CNVs, 368 unique CNV regions were detected. Among them, there were 76 common CNVRs with > 1% CNV frequency. Together, these CNVRs contained 538 genes. Heritability errors of 156 bovine pedigrees and comparative pairwise analyses were analyzed to detect 448 common deletion polymorphisms. Identified variations in this study were successfully validated using visual examination of the genoplot image, Mendelian inconsistency, another CNV identification program, and quantitative PCR.

Conclusions
In this study, we describe a map of bovine CNVs and provide important resources for future bovine genome research. This result will contribute to animal breeding and protection from diseases with the aid of genomic information.
A scenario of mitochondrial genome evolution in maize based on rearrangement events
Authors: Darracq Aude , Varré Jean-Stéphane , Touzet Pascal 
Published: April 2010

Abstract

Background
Despite their monophyletic origin, animal and plant mitochondrial genomes have been described as exhibiting different modes of evolution. Indeed, plant mitochondrial genomes feature a larger size, a lower mutation rate and more rearrangements than their animal counterparts. Gene order variation in animal mitochondrial genomes is often described as being due to translocation and inversion events, but tandem duplication followed by loss has also been proposed as an alternative process. In plant mitochondrial genomes, at the species level, gene shuffling and duplicate occurrence are such that no clear phylogeny has ever been identified, when considering genome structure variation.

Results
In this study we analyzed the whole sequences of eight mitochondrial genomes from maize and teosintes in order to comprehend the events that led to their structural features, i.e. the order of genes, tRNAs, rRNAs, ORFs, pseudogenes and non-coding sequences shared by all mitogenomes and duplicate occurrences. We suggest a tandem duplication model similar to the one described in animals, except that some duplicates can remain. This model enabled us to develop a manual method to deal with duplicates, a recurrent problem in rearrangement analyses. The phylogenetic tree exclusively based on rearrangement and duplication events is congruent with the tree based on sequence polymorphism, validating our evolution model.

Conclusions
This study suggests more similarity than usually reported between plant and animal mitochondrial genomes in their mode of evolution. Further work will consist of developing new tools in order to automatically look for signatures of tandem duplication events in other plant mitogenomes and evaluate the occurrence of this process on a larger scale.
Evolutionary conservation of essential and highly expressed genes in Pseudomonas aeruginosa
Authors: Dötsch Andreas , Klawonn Frank , Jarek Michael , Scharfe Maren , Blöcker Helmut , Häussler Susanne 
Published: April 2010

AbstractBackgroundThe constant increase in development and spread of bacterial resistance to antibiotics poses a serious threat to human health. New sequencing technologies are now on the horizon that will yield massive increases in our capacity for DNA sequencing and will revolutionize the drug discovery process. Since essential genes are promising novel antibiotic targets, the prediction of gene essentiality based on genomic information has become a major focus.ResultsIn this study we demonstrate that pooled sequencing is applicable for the analysis of sequence variations of strain collections with more than 10 individual isolates. Pooled sequencing of 36 clinicalPseudomonas aeruginosaisolates revealed that essential and highly expressed proteins evolve at lower rates, whereas extracellular proteins evolve at higher rates. We furthermore refined the list of experimentally essentialP. aeruginosagenes, and identified 980 genes that show no sequence variation at all. Among the conserved nonessential genes we found several that are involved in regulation, motility and virulence, indicating that they represent factors of evolutionary importance for the lifestyle of a successful environmental bacterium and opportunistic pathogen.ConclusionThe detailed analysis of a comprehensive set ofP. aeruginosagenomes in this study clearly disclosed detailed information of the genomic makeup and revealed a large set of highly conserved genes that play an important role for the lifestyle of this microorganism. Sequencing strain collections enables for a detailed and extensive identification of sequence variations as potential bacterial adaptation processes, e.g., during the development of antibiotic resistance in the clinical setting and thus may be the basis to uncover putative targets for novel treatment strategies.
Gauging knowledge of developmental milestones among Albertan adults: a cross-sectional survey
Authors: Rikhy Shivani , Tough Suzanne , Trute Barry , Benzies Karen , Kehler Heather , Johnston David W 
Published: April 2010

AbstractBackgroundParental knowledge of child development has been associated with more effective parenting strategies and better child outcomes. However, little is known about what adults who interact with children under the age of 14 years know about child development.MethodsBetween September 2007 and March 2008, computer assisted telephone interviews were completed with 1443 randomly selected adults. Adults were eligible if they had interacted with a child less than 14 years of age in the past six months and lived in Alberta, Canada.ResultsSixty three percent of respondents answered two (or more) out of four questions on physical development correctly. Fifteen percent of respondents answered two (or more) out of three questions on cognitive development correctly. Seven percent of respondents answered three (or more) out of five questions on social development correctly. Two percent of respondents answered three (or more) out of five questions on emotional development correctly. Parents and females were better able to identify physical developmental milestones compared to non-parents and males. 81% of adults correctly responded that a child's experience in the first year of life has an important impact on later school performance, 70% correctly responded that a child's ability to learn is not set from birth, 50% of adults correctly responded that children learn more from hearing someone speak than from television, and 45% recognized that parents' emotional closeness with a baby influences later achievement. Parents were most likely to use doctors/paediatricians, books, and nurses as resources. Among parents, there was no relationship between knowledge and parenting morale.ConclusionsThe majority of adults were unable to correctly answer questions related to when children under six years of age typically achieve developmental milestones. Knowledge of physical development exceeded knowledge about cognitive, emotional and social development. Adults were aware of the importance of positive experiences in influencing children's development. Strategies to improve awareness of developmental milestones combined with information on how to support optimal development may improve child development outcomes. Given that parents seek information about child development from health care providers there is an opportunity to ensure that providers are well informed about child development.
Gene expression in nontumoral liver tissue and recurrence-free survival in hepatitis C virus-positive hepatocellular carcinoma
Authors: Tsuchiya Masato , Parker Joel S. , Kono Hiroshi , Matsuda Masanori , Fujii Hideki , Rusyn Ivan 
Published: April 2010

AbstractBackgroundThe goal of this study was to understand gene expression signatures of hepatocellular carcinoma (HCC) recurrence in subjects with hepatitis C virus (HCV) infection. Recurrence-free survival (RFS) following curative resection of HCC in subjects with HCV is highly variable. Traditional clinico-pathological endpoints are recognized as weak predictors of RFS. It has been suggested that gene expression profiling of HCC and nontumoral liver tissue may improve prediction of RFS, aid in understanding of the underlying liver disease, and guide individualized patient management. Frozen samples of the tumors and nontumoral liver were obtained from 47 subjects with HCV-associated HCC. Additional nontumoral liver samples were obtained from HCV-free subjects with metastatic liver tumors. Gene expression profiling data was used to determine the molecular signature of HCV-associated HCC and to develop a predictor of RFS.ResultsThe molecular profile of the HCV-associated HCC confirmed central roles for MYC and TGFβ1 in liver tumor development. Gene expression in tumors was found to have poor predictive power with regards to RFS, but analysis of nontumoral tissues yielded a strong predictor for RFS in late-recurring (>1 year) subjects. Importantly, nontumoral tissue-derived gene expression predictor of RFS was highly significant in both univariable and multivariable Cox proportional hazard model analyses.ConclusionsMicroarray analysis of the nontumoral tissues from subjects with HCV-associated HCC delivers novel molecular signatures of RFS, especially among the late-recurrence subjects. The gene expression predictor may hold important insights into the pathobiology of HCC recurrence andde novotumor formation in cirrhotic patients.
Methodological constraints in interpreting serum paraoxonase-1 activity measurements: an example from a study in HIV-infected patients
Authors: Parra Sandra , Marsillach Judit , Aragonès Gerard , Rull Anna , Beltrán-Debón Raúl , Alonso-Villaverde Carlos , Joven Jorge , Camps Jordi 
Published: April 2010

Abstract

Background
Paraoxonase-1 (PON1) is an antioxidant enzyme that attenuates the production of the monocyte chemoattractant protein-1 (MCP-1) in vitro. Although oxidation and inflammation are closely related processes, the association between PON1 and MCP-1 has not been completely characterised due, probably, to that the current use of synthetic substrates for PON1 measurement limits the interpretation of the data. In the present study, we explored the relationships between the circulating levels of PON1 and MCP-1 in human immunodeficiency virus-infected patients in relation to the multifunctional capabilities of PON1.

Methods
We measured selected variables in 227 patients and in a control group of 409 participants. Serum PON1 esterase and lactonase activities were measured as the rates of hydrolysis of paraoxon and of 5-(thiobutyl)-butyrolactone, respectively. Oxidised LDL and MCP-1 concentrations were determined by enzyme-linked immunosorbent assay. High-density lipoproteins cholesterol, apolipoprotein A-I, and C-reactive protein concentrations were measured by standard automated methods.

Results
There were significant relationships between PON1 activity and several indices of oxidation and inflammation in control subjects and in infected patients. However, these relationships varied not only with disease status but also on the type of substrate used for PON1 measurement.

Conclusion
The present study is a cautionary tale highlighting that results of clinical studies on PON1 may vary depending on the methods used as well as the disease studied. Until more specific methods using physiologically-akin substrates are developed for PON1 measurement, we suggest the simultaneous employment of at least two different substrates in order to improve the reliability of the results obtained.
Quality prevails over identity in the sexually selected vocalisations of an ageing mammal
Authors: Briefer Elodie , Vannoni Elisabetta , McElligott Alan G 
Published: April 2010

Abstract

Background
Male sexually selected vocalisations generally contain both individuality and quality cues that are crucial in intra- as well as inter-sexual communication. As individuality is a fixed feature whereas male phenotypic quality changes with age, individuality and quality cues may be subjected to different selection pressures over time. Individuality (for example, morphology of the vocal apparatus) and quality (for example, body size and dominance status) can both affect the vocal production mechanism, inducing the same components of vocalisations to convey both kinds of information. In this case, do quality-related changes to the acoustic structure of calls induce a modification of vocal cues to identity from year to year? We investigated this question in fallow deer (Dama dama), in which some acoustic parameters of vocalisations (groans) code for both individuality and quality.

Results
We carried out a longitudinal analysis of groan individuality, examining the effects of age and dominance rank on the acoustic structure of groans of the same males recorded during consecutive years. We found both age- and rank-related changes to groans; the minimum values of the highest formant frequencies and the fundamental frequency increased with the age of males and they decreased when males became more dominant. Both age- and rank-related acoustic parameters contributed to individuality. Male quality changed with age, inducing a change in quality-related parameters and thus, a modification of vocal cues to male individuality between years.

Conclusions
The encoding of individuality and quality information in the same components of vocalisations induces a tradeoff between these two kinds of signals over time. Fallow deer vocalisations are honest signals of quality that are not fixed over time but are modified dynamically according to male quality. As they are more reliable cues to quality than to individuality, they may not be used by conspecifics to recognize a given male from one year to another, but potentially used by both sexes to assess male quality during each breeding season.
Limelight on two HIV/SIV accessory proteins in macrophage infection: Is Vpx overshadowing Vpr?
Authors: Ayinde Diana , Maudet Claire , Transy Catherine , Margottin-Goguet Florence 
Published: April 2010

AbstractHIV viruses encode a set of accessory proteins, which are important determinants of virulence due to their ability to manipulate the host cell physiology for the benefit of the virus. Although these viral proteins are dispensable for viral growth in manyin vitrocell culture systems, they influence the efficiency of viral replication in certain cell types. Macrophages are early targets of HIV infection which play a major role in viral dissemination and persistence in the organism. This review focuses on two HIV accessory proteins whose functions might be more specifically related to macrophage infection: Vpr, which is conserved across primate lentiviruses including HIV-1 and HIV-2, and Vpx, a protein genetically related to Vpr, which is unique to HIV-2 and a subset of simian lentiviruses. Recent studies suggest that both Vpr and Vpx exploit the host ubiquitination machinery in order to inactivate specific cellular proteins. We review here why it remains difficult to decipher the role of Vpr in macrophage infection by HIV-1 and how recent data underscore the ability of Vpx to antagonize a restriction factor which counteracts synthesis of viral DNA in monocytic cells.