bluuebunny/crossref_metadata_2025_split huggingface dataset:
A quantitative linkage score for an association study following a linkage analysis
Authors: Wang Tao , Elston Robert C 
Published: January 2006

Abstract

Background:
Currently, a commonly used strategy for mapping complex quantitative traits is to use a genome-wide linkage analysis to narrow suspected genes to regions on a scale of centiMorgans (cM), followed by an association analysis to fine map the genetic variation in regions showing linkage. Two important questions arise in the design and the resulting inference at the association stage of this sequential procedure: (1) how should we design an efficient association study given the information provided by the previous linkage study? and (2) can an association in a linkage region explain, in part, the detected linkage signal?

Results:
We derive a quantitative linkage score (QLS) based on Haseman-Elston regression (Haseman and Elston 1972) and make use of this score to address both questions. In designing an association study, the selection of a subsample from the linkage study sample can be guided by the linkage information summarized in the QLS. When heterogeneity exists, we show that selection based on the QLS can increase the proportion of sample individuals from the subpopulation affected by a disease allele and therefore greatly improves the power of the association study. For the resulting inference, we frame as a hypothesis test the question of whether a linkage signal in a region can be in part explained by a marker allele. A simple one sided paired t-statistic is defined by comparing the two sets of QLSs obtained with/without modeling a marker association: a significant difference indicates that the marker can at least partly account for the detected linkage. We also show that this statistic can be used to detect a spurious association.

Conclusion:
All our results suggest that a careful examination of QLSs should be helpful for understanding the results of both association and linkage studies.
The Epc-N domain: a predicted protein-protein interaction domain found in select chromatin associated proteins
Authors: Perry Jason 
Published: January 2006

Abstract

Background
An underlying tenet of the epigenetic code hypothesis is the existence of protein domains that can recognize various chromatin structures. To date, two major candidates have emerged: (i) the bromodomain, which can recognize certain acetylation marks and (ii) the chromodomain, which can recognize certain methylation marks.

Results
The Epc-N (E nhancer of P olyc omb-N-terminus) domain is formally defined herein. This domain is conserved across eukaryotes and is predicted to form a right-handed orthogonal four-helix bundle with extended strands at both termini. The types of amino acid residues that define the Epc-N domain suggest a role in mediating protein-protein interactions, possibly specifically in the context of chromatin binding, and the types of proteins in which it is found (known components of histone acetyltransferase complexes) strongly suggest a role in epigenetic structure formation and/or recognition. There appear to be two major Epc-N protein families that can be divided into four unique protein subfamilies. Two of these subfamilies (I and II) may be related to one another in that subfamily I can be viewed as a plant-specific expansion of subfamily II. The other two subfamilies (III and IV) appear to be related to one another by duplication events in a primordial fungal-metazoan-mycetozoan ancestor. Subfamilies III and IV are further defined by the presence of an evolutionarily conserved five-center-zinc-binding motif in the loop connecting the second and third helices of the four-helix bundle. This m otif appears to consist of a P HD followed by a mononuclear Z n knuckle, followed by a P HD-like derivative, and will thus be referred to as the PZPM. All non-Epc-N proteins studied thus far that contain the PZPM have been implicated in histone methylation and/or gene silencing. In addition, an unusual phyletic distribution of Epc-N-containing proteins is observed.

Conclusion
The data suggest that the Epc-N domain is a protein-protein interaction module found in chromatin associated proteins. It is possible that the Epc-N domain serves as a direct link between histone acetylation and methylation statuses. The unusual phyletic distribution of Epc-N-containing proteins may provide a conduit for future insight into how different organisms form, perceive and respond to epigenetic information.
Evidence of host-virus co-evolution in tetranucleotide usage patterns of bacteriophages and eukaryotic viruses
Authors: Pride David T , Wassenaar Trudy M , Ghose Chandrabali , Blaser Martin J 
Published: January 2006

Abstract

Background
Virus taxonomy is based on morphologic characteristics, as there are no widely used non-phenotypic measures for comparison among virus families. We examined whether there is phylogenetic signal in virus nucleotide usage patterns that can be used to determine ancestral relationships. The well-studied model of tail morphology in bacteriophage classification was used for comparison with nucleotide usage patterns. Tetranucleotide usage deviation (TUD) patterns were chosen since they have previously been shown to contain phylogenetic signal similar to that of 16S rRNA.

Results
We found that bacteriophages have unique TUD patterns, representing genomic signatures that are relatively conserved among those with similar host range. Analysis of TUD-based phylogeny indicates that host influences are important in bacteriophage evolution, and phylogenies containing both phages and their hosts support their co-evolution. TUD-based phylogeny of eukaryotic viruses indicates that they cluster largely based on nucleic acid type and genome size. Similarities between eukaryotic virus phylogenies based on TUD and gene content substantiate the TUD methodology.

Conclusion
Differences between phenotypic and TUD analysis may provide clues to virus ancestry not previously inferred. As such, TUD analysis provides a complementary approach to morphology-based systems in analysis of virus evolution.
Analysis of and function predictions for previously conserved hypothetical or putative proteins in Blochmannia floridanus
Authors: Gaudermann Peter , Vogl Ina , Zientz Evelyn , Silva Francisco J , Moya Andres , Gross Roy , Dandekar Thomas 
Published: January 2006

Abstract

Background
There is an increasing interest to better understand endosymbiont capabilities in insects both from an ecological point of view and for pest control. Blochmannia floridanus provides important nutrients for its host, the ant Camponotus, while the bacterium in return is provided with a niche to proliferate. Blochmannia floridanus proteins and metabolites are difficult to study due to its endosymbiontic life style; however, its complete genome sequence became recently available.

Results
Improved sequence analysis algorithms, databanks and gene and pathway context methods allowed us to reveal new information on various enzyme and pathways from the Blochmannia floridanus genome sequence [EMBL-ID BX248583]. Furthermore, these predictions are supported and linked to experimental data for instance from structural genomics projects (e.g. Bfl341, Bfl 499) or available biochemical data on proteins from other species which we show here to be related. We were able to assign a confirmed or at least a putative molecular function for 21 from 27 previously conserved hypothetical proteins. For 48 proteins of 66 with a previous putative assignment the function was further clarified. Several of these proteins occur in many proteobacteria and are found to be conserved even in the compact genome of this endosymbiont. To extend and re-test predictions and links to experimentally verified protein functions, functional clusters and interactions were assembled. These included septum initiation and cell division (Bfl165, Bfl303, Bfl248 et al.); translation; transport; the ubiquinone (Bfl547 et al.), the inositol and nitrogen pathways.

Conclusion
Taken together, our data allow a better and more complete description of the pathway capabilities and life style of this typical endosymbiont.
Lipid-soluble smoke particles damage endothelial cells and reduce endothelium-dependent dilatation in rat and man
Authors: Zhang Jin-Yan , Cao Yong-Xiao , Xu Cang-Bao , Edvinsson Lars 
Published: January 2006

Abstract

Background
Cigarette smoking is a strong risk factor for vascular disease and known to cause dysfunction of the endothelium. However, the molecular mechanisms involved are still not fully understood.

Methods
In order to reveal the direct effects of lipid-soluble smoke particles on the endothelium, ring segments isolated from rat mesenteric arteries and human middle cerebral arteries (MCA) obtained at autopsy were incubated for 6 to 48 hrs in the presence of dimethylsulphoxide (DMSO)-soluble particles from cigarette smoke (DSP), i.e. lipid-soluble smoke particles. The endothelial microstructure was examined by transmission electron microscopy. The endothelial function was evaluated by acetylcholine (ACh)-induced endothelium-dependent vasodilatation, using a sensitive myograph.

Results
After DSP treatment, the arterial endothelium was swollen and loosing its attachment. In functional tests, the total ACh-induced dilatation, the nitric oxide (NO)-mediated and the endothelium-derived hyperpolarization factor (EDHF)-mediated dilatations were significantly decreased by DSP in a time- and concentration-dependent manner (p < 0.05). Nicotine, an important compound in cigarette smoke had, in an equivalent concentration as in DSP, no such effects (p > 0.05). Similar results were obtained in the human MCA.

Conclusion
Thus, we demonstrate that the lipid-soluble smoke particles, but not nicotine, caused damage to arterial endothelium and reduced the endothelium-dependent dilatation in man and rat.
The use of adherence aids by adults with diabetes: A cross-sectional survey
Authors: Littenberg Benjamin , MacLean Charles D , Hurowitz Laurie 
Published: January 2006

Abstract

Background
Adherence with medication taking is a major barrier to physiologic control in diabetes and many strategies for improving adherence are in use. We sought to describe the use of mnemonic devices and other adherence aids by adults with diabetes and to investigate their association with control of hyperglycemia, hyperlipidemia and hypertension.

Methods
Cross sectional survey of diabetic adults randomly selected from Primary Care practices in the Vermont Diabetes Information System. We used linear regression to examine the associations between the use of various aids and physiologic control among subjects who used oral agents for hyperglycemia, hypercholesterolemia, and hypertension.

Results
289 subjects (mean age 65.4 years; 51% female) used medications for all three conditions. Adherence aids were reported by 80%. The most popular were day-of-the-week pill boxes (50%), putting the pills in a special place (41%), and associating pill taking with a daily event such as a meal, TV show, or bedtime (11%). After adjusting for age, sex, marital status, income, and education, those who used a special place had better glycemic control (A1C -0.36%; P = .04) and systolic blood pressure (-5.9 mm Hg; P = .05) than those who used no aids. Those who used a daily event had better A1C (-0.56%; P = .01) than patients who used no aids.

Conclusion
Although adherence aids are in common use among adults with diabetes, there is little evidence that they are efficacious. In this study, we found a few statistically significant associations with adherence aids and better diabetes control. However, these findings could be attributed to multiple comparisons or unmeasured confounders. Until more rigorous evaluations are available, it seems reasonable to recommend keeping medicines in a special place for diabetic adults prescribed multiple medications.
Humoral immune response to MUC5AC in patients with colorectal polyps and colorectal carcinoma
Authors: Kocer Belma , McKolanis John , Soran Atilla 
Published: January 2006

AbstractBackgroundMUC5AC is a secreted mucin aberrantly expressed by colorectal polyps and carcinoma. It has been hypothesized that aberrant expression of MUC5AC in colorectal carcinoma tissues increased the overall survival of patients with colorectal carcinoma. The present study investigates the incidence of naturally occurring MUC5AC antibodies in the sera of normal individuals, patients with colonic polyps and patients with advanced colorectal carcinoma. A second aim was to determine the relationship of MUC5AC antibody with the prognosis of colorectal carcinoma.MethodsFree circulating MUC5AC antibodies were measured using an enzyme-linked immunosorbent assay with a synthetic peptide corresponding to an 8 aa. segment of MUC5AC tandem repeat region. Immunohistochemical analysis was completed to demonstrate MUC5AC expression in the polyp specimens.ResultsMUC5AC antibodies were detected in 6 of 22 (27.3%) healthy subjects, 9 of 20 (45%) polyp patients, 18 of 30 (60%) patients with colorectal cancer. The presence of circulating free MUC5AC antibody levels was significantly correlated with expression of MUC5AC in polyp sections. Serum MUC5AC antibody positivity was higher in patients with colon located tumors, advanced stage and poorly differentiated tumors were found negatively affecting patient survival in our study. MUC5AC antibody positivity was higher in patients with poor prognostic parameters. Disease free survival and overall survival were shorter in this group of patients. In the multivariate analysis MUC5AC antibody positivity didn't find an independent prognostic factor on prognosis.ConclusionDecreased survival in colorectal carcinoma patients with MUC5AC antibody positivity may be due to a decrease in the MUC5AC expression in tumor tissues of surviving carcinoma patients.
Prevalence of inappropriate medication using Beers criteria in Japanese long-term care facilities
Authors: Niwata Satoko , Yamada Yukari , Ikegami Naoki 
Published: January 2006

Abstract

Background
The prevalence and risk factors of potentially inappropriate medication use among the elderly patients have been studied in various countries, but because of the difficulty of obtaining data on patient characteristics and medications they have not been studied in Japan.

Methods
We conducted a retrospective cross-sectional study in 17 Japanese long-term care (LTC) facilities by collecting data from the comprehensive MDS assessment forms for 1669 patients aged 65 years and over who were assessed between January and July of 2002. Potentially inappropriate medications were identified on the basis of the 2003 Beers criteria.

Results
The patients in the sample were similar in terms of demographic characteristics to those in the national survey. Our study revealed that 356 (21.1%) of the patients were treated with potentially inappropriate medication independent of disease or condition. The most commonly inappropriately prescribed medication was ticlopidine, which had been prescribed for 107 patients (6.3%). There were 300 (18.0%) patients treated with at least 1 inappropriate medication dependent on the disease or condition. The highest prevalence of inappropriate medication use dependent on the disease or condition was found in patients with chronic constipation. Multiple logistic regression analysis revealed psychotropic drug use (OR = 1.511), medication cost of per day (OR = 1.173), number of medications (OR = 1.140), and age (OR = 0.981) as factors related to inappropriate medication use independent of disease or condition. Neither patient characteristics nor facility characteristics emerged as predictors of inappropriate prescription.

Conclusion
The prevalence and predictors of inappropriate medication use in Japanese LTC facilities were similar to those in other countries.
Mutation analysis of SDHB and SDHC: novel germline mutations in sporadic head and neck paraganglioma and familial paraganglioma and/or pheochromocytoma
Authors: Bayley Jean-Pierre , van Minderhout Ivonne , Weiss Marjan M , Jansen Jeroen C , Oomen Peter HN , Menko Fred H , Pasini Barbara , Ferrando Barbara , Wong Nora , Alpert Lesley C , Williams Rosie , Blair Edward , Devilee Peter , Taschner Peter EM 
Published: January 2006

Abstract

Background
Germline mutations of the SDHD, SDHB and SDHC genes, encoding three of the four subunits of succinate dehydrogenase, are a major cause of hereditary paraganglioma and pheochromocytoma, and demonstrate that these genes are classic tumor suppressors. Succinate dehydrogenase is a heterotetrameric protein complex and a component of both the Krebs cycle and the mitochondrial respiratory chain (succinate:ubiquinone oxidoreductase or complex II).

Methods
Using conformation sensitive gel electrophoresis (CSGE) and direct DNA sequencing to analyse genomic DNA from peripheral blood lymphocytes, here we describe the mutation analysis of the SDHB and SDHC genes in 37 patients with sporadic (i.e. no known family history) head and neck paraganglioma and five pheochromocytoma and/or paraganglioma families.

Results
Two sporadic patients were found to have a SDHB splice site mutation in intron 4, c.423+1G>A, which produces a mis-spliced transcript with a 54 nucleotide deletion, resulting in an 18 amino acid in-frame deletion. A third patient was found to carry the c.214C>T (p.Arg72Cys) missense mutation in exon 4 of SDHC, which is situated in a highly conserved protein motif that constitutes the quinone-binding site of the succinate: ubiquinone oxidoreductase (SQR) complex in E. coli. Together with our previous results, we found 27 germline mutations of SDH genes in 95 cases (28%) of sporadic head and neck paraganglioma. In addition all index patients of five families showing hereditary pheochromocytoma-paraganglioma were found to carry germline mutations of SDHB: four of which were novel, c.343C>T (p.Arg115X), c.141G>A (p.Trp47X), c.281G>A (p.Arg94Lys), and c.653G>C (p.Trp218Ser), and one reported previously, c.136C>T, p.Arg46X.

Conclusion
In conclusion, these data indicate that germline mutations of SDHB and SDHC play a minor role in sporadic head and neck paraganglioma and further underline the importance of germline SDHB mutations in cases of familial pheochromocytoma-paraganglioma.
Factor VII deficiency and developmental abnormalities in a patient with partial monosomy of 13q and trisomy of 16p: case report and review of the literature
Authors: Brooks Brian P , Meck Jeanne M , Haddad Bassem R , Bendavid Claude , Blain Delphine , Toretsky Jeffrey A 
Published: January 2006

AbstractBackgroundUnbalanced chromosomal translocations may present with a variety of clinical and laboratory findings and provide insight into the functions of genes on the involved chromosomal segments.Case PresentationA 9 year-old boy presented to our clinic with Factor VII deficiency, microcephaly, a seizure disorder, multiple midline abnormalities (agenesis of the corpus callosum, imperforate anus, bilateral optic nerve hypoplasia), developmental delay, hypopigmented macules, short 5thfingers, and sleep apnea due to enlarged tonsils. Cytogenetic and fluorescencein situhybridization analyses revealed an unbalanced translocation involving the segment distal to 16p13 replacing the segment distal to 13q33 [46, XY, der(13)t(13;16)(q33;p13.3)]. Specific BAC-probes were used to confirm the extent of the 13q deletion.ConclusionThis unique unbalanced chromosomal translocation may provide insights into genes important in midline development and underscores the previously-reported phenotype of Factor VII deficiency in 13q deletions.
Influence of advanced age of maternal grandmothers on Down syndrome
Authors: Malini Suttur S , Ramachandra Nallur B 
Published: January 2006

Abstract

Background
Down syndrome (DS) is the most common chromosomal anomaly associated with mental retardation. This is due to the occurrence of free trisomy 21 (92–95%), mosaic trisomy 21 (2–4%) and translocation (3–4%). Advanced maternal age is a well documented risk factor for maternal meiotic nondisjunction. In India three children with DS are born every hour and more DS children are given birth to by young age mothers than by advanced age mothers. Therefore, detailed analysis of the families with DS is needed to find out other possible causative factors for nondisjunction.

Methods
We investigated 69 families of cytogenetically confirmed DS children and constructed pedigrees of these families. We also studied 200 randomly selected families belonging to different religions as controls. Statistical analysis was carried out using logistic regression.

Results
Out of the 69 DS cases studied, 67 were free trisomy 21, two cases were mosaic trisomy 21 and there were none with translocation. The number of DS births was greater for the young age mothers compared with the advanced age mothers. It has also been recorded that young age mothers (18 to 29 years) born to their mothers at the age 30 years and above produced as high as 91.3% of children with DS. The logistic regression of case- control study of DS children revealed that the odds ratio of age of grandmother was significant when all the four variables were used once at a time. However, the effect of age of mother and father was smaller than the effect of age of maternal grandmother. Therefore, for every year of advancement of age of the maternal grandmother, the risk (odds) of birth of DS baby increases by 30%.

Conclusion
Besides the known risk factors, mother's age, father's age, the age of the maternal grandmother at the time of birth of the mother is a risk factor for the occurrence of Down syndrome.
Population-based neuropathological studies of dementia: design, methods and areas of investigation – a systematic review
Authors: Zaccai Julia , Ince Paul , Brayne Carol 
Published: January 2006

Abstract

Background
Prospective population-based neuropathological studies have a special place in dementia research which is under emphasised.

Methods
A systematic review of the methods of population-based neuropathological studies of dementia was carried out. These studies were assessed in relation to their representativeness of underlying populations and the clinical, neuropsychological and neuropathological approaches adopted.

Results
Six studies were found to be true population-based neuropathological studies of dementia in the older people: the Hisayama study (Japan); Vantaa 85+ study (Finland); CC75C study (Cambridge, UK); CFAS (multicentre, UK); Cache County study (Utah, USA); HAAS (Hawaï, USA). These differ in the core characteristics of their populations. The studies used standardised neuropathological methods which facilitate analyses on: clinicopathological associations and confirmation of diagnosis, assessing the validity of hierarchical models of neuropathological lesion burden; investigating the associations between neuropathological burden and risk factors including genetic factors. Examples of findings are given although there is too little overlap in the areas investigated amongst these studies to form the basis of a systematic review of the results.

Conclusion
Clinicopathological studies based on true population samples can provide unique insights in dementia. Individually they are limited in power and scope; together they represent a powerful source to translate findings from laboratory to populations.