bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomics of glycopeptidolipid biosynthesis in Mycobacterium abscessus and M. chelonae
Authors: Ripoll Fabienne , Deshayes Caroline , Pasek Sophie , Laval Françoise , Beretti Jean-Luc , Biet Franck , Risler Jean-Loup , Daffé Mamadou , Etienne Gilles , Gaillard Jean-Louis , Reyrat Jean-Marc 
Published: May 2007

Abstract

Background
The outermost layer of the bacterial surface is of crucial importance because it is in constant interaction with the host. Glycopeptidolipids (GPLs) are major surface glycolipids present on various mycobacterial species. In the fast-grower model organism Mycobacterium smegmatis, GPL biosynthesis involves approximately 30 genes all mapping to a single region of 65 kb.

Results
We have recently sequenced the complete genomes of two fast-growers causing human infections, Mycobacterium abscessus (CIP 104536T) and M. chelonae (CIP 104535T). We show here that these two species contain genes corresponding to all those of the M. smegmatis "GPL locus", with extensive conservation of the predicted protein sequences consistent with the production of GPL molecules indistinguishable by biochemical analysis. However, the GPL locus appears to be split into several parts in M. chelonae and M. abscessus. One large cluster (19 genes) comprises all genes involved in the synthesis of the tripeptide-aminoalcohol moiety, the glycosylation of the lipopeptide and methylation/acetylation modifications. We provide evidence that a duplicated acetyltransferase (atf1 and atf2) in M. abscessus and M. chelonae has evolved through specialization, being able to transfer one acetyl at once in a sequential manner. There is a second smaller and distant (M. chelonae, 900 kb; M. abscessus, 3 Mb) cluster of six genes involved in the synthesis of the fatty acyl moiety and its attachment to the tripeptide-aminoalcohol moiety. The other genes are scattered throughout the genome, including two genes encoding putative regulatory proteins.

Conclusion
Although these three species produce identical GPL molecules, the organization of GPL genes differ between them, thus constituting species-specific signatures. An hypothesis is that the compact organization of the GPL locus in M. smegmatis represents the ancestral form and that evolution has scattered various pieces throughout the genome in M. abscessus and M. chelonae.
N-glycan alterations are associated with drug resistance in human hepatocellular carcinoma
Authors: Kudo Takeaki , Nakagawa Hiroaki , Takahashi Masato , Hamaguchi Jun , Kamiyama Naoya , Yokoo Hideki , Nakanishi Kazuaki , Nakagawa Takahito , Kamiyama Toshiya , Deguchi Kisaburo , Nishimura Shin-Ichiro , Todo Satoru 
Published: May 2007

Abstract

Background
Correlations of disease phenotypes with glycosylation changes have been analysed intensively in the tumor biology field. Glycoforms potentially associated with carcinogenesis, tumor progression and cancer metastasis have been identified. In cancer therapy, drug resistance is a severe problem, reducing therapeutic effect of drugs and adding to patient suffering. Although multiple mechanisms likely underlie resistance of cancer cells to anticancer drugs, including overexpression of transporters, the relationship of glycans to drug resistance is not well understood.

Results
We established epirubicin (EPI) – and mitoxantrone (MIT) – resistant cell lines (HLE-EPI and HLE-MIT) from the human hepatocellular carcinoma cell line (HLE). HLE-EPI and HLE-MIT overexpressed transporters MDR1/ABCB1 and BCRP/ABCG2, respectively. Here we compared the glycomics of HLE-EPI and HLE-MIT cells with the parental HLE line. Core fucosylated triantennary oligosaccharides were increased in the two resistant lines. We investigated mRNA levels of glycosyltransferases synthesizing this oligosaccharide, namely, N-acetylglucosaminyltransferase (GnT)-IVa, GnT-IVb and α1,6-fucosyltransferase (α1,6-FucT), and found that α1,6-FucT was particularly overexpressed in HLE-MIT cells. In HLE-EPI cells, GnT-IVa expression was decreased, while GnT-IVb was increased. Both GnT-IVs were downregulated in HLE-MIT cells. HLE-MIT cells also showed decreases in fucosylated tetraantennary oligosaccharide, the product of GnT-V. GnT-V expression was decreased in both lines, but particularly so in HLE-MIT cells. Thus both N-glycan and glycosyltransferase expression was altered as cells acquired tolerance, suggesting novel mechanisms of drug resistance.

Conclusion
N-glycan and glycosyltransferase expression in HLE-EPI and HLE-MIT were analysed and presented that glycans altered according with acquired tolerance. These results suggested novel mechanisms of drug resistance.
p27kip1: a target for tumor therapies?
Authors: Nickeleit Irina , Zender Steffen , Kossatz Uta , Malek Nisar P 
Published: May 2007

Abstract
The cyclin kinase inhibitor p27kip1 acts as a potent tumor supressor protein in a variety of human cancers. Its expression levels correlate closely with the overall prognosis of the affected patient and often predict the outcome to different treatment modalities. In contrast to other tumor suppressor proteins p27 expression levels in tumor cells are frequently regulated by ubiquitin dependent proteolysis. Re-expression of p27 in cancer cells therefore does not require gene therapy but can be achieved by interfering with the protein turnover machinery. In this review we will summarize experimental results which highlight the potential use of p27 as a target for oncological therapies.
cis-Decoder discovers constellations of conserved DNA sequences shared among tissue-specific enhancers
Authors: Brody Thomas , Rasband Wayne , Baler Kevin , Kuzin Alexander , Kundu Mukta , Odenwald Ward F 
Published: May 2007

AbstractA systematic approach is described for analysis of evolutionarily conserved cis-regulatory DNA using cis-Decoder, a tool for discovery of conserved sequence elements that are shared between similarly regulated enhancers. Analysis of 2,086 conserved sequence blocks (CSBs), identified from 135 characterized enhancers, reveals most CSBs consist of shorter overlapping/adjacent elements that are either enhancer type-specific or common to enhancers with divergent regulatory behaviors. Our findings suggest that enhancers employ overlapping repertoires of highly conserved core elements.
Study of Association between Common Variation in the Insulin-Like Growth Factor 2 Gene and Indices of Obesity and Body Size in Middle-Aged Men and Women
Authors: Heude Barbara , Ong Ken K. , Luben Robert , Wareham Nicholas J. , Sandhu Manjinder S. 
Published: May 2007

Abstract
Context: The IGF2 gene (IGF2) plays a key role in growth and is a candidate for association with obesity. Previous studies have reported that polymorphisms in IGF2 are associated with body weight and body mass index (BMI), but the results have been inconsistent.
Objectives: The aim of this study was primarily to confirm the association with BMI and, secondarily, to study the associations with other indices of body size.
Methods: In a sample of 2797 women and 2203 men aged 39–79 participating in the Norfolk arm of the European Prospective Investigation of Cancer, we genotyped three single nucleotide polymorphisms (SNPs) in the IGF2 gene that were previously associated with BMI [6815 A/T, 1156 T/C (G/A), and 820 G/A (ApaI)].
Results: No significant associations were observed between these SNPs and BMI. However, all three SNPs were significantly associated with height (P = 0.03 to 0.001). In a backward elimination regression analysis, two SNPs, 1156 T/C (G/A) and 820 G/A, remained independently associated with height (P = 0.003 and P = 0.038, respectively). Haplotype analysis of these two SNPs showed that carriers of the GA haplotype were shorter than carriers of each of the other three haplotypes (P &lt; 0.001 for all comparisons).
Conclusions: We did not confirm the previously reported associations between IGF2 polymorphisms and BMI. However, our results suggest that common variation in the IGF2 gene may be associated with adult height. IGF2 could be considered as a candidate gene for future research on mechanisms for the association between height and chronic diseases, such as cancer, diabetes, and coronary heart disease.
Evidence for Allograft Rejection in an Islet Transplant Recipient and Effect on β-Cell Secretory Capacity
Authors: Rickels Michael R. , Kamoun Malek , Kearns Jane , Markmann James F. , Naji Ali 
Published: May 2007

AbstractContext: The majority of islet transplant recipients experience a gradual decline in islet graft function, but the identification of islet-specific immune responses remains uncommon.Objectives: The aim was to present a case in which decline in islet graft function was accompanied by the appearance of islet donor-specific alloantibodies and demonstrate the effect on β-cell secretory capacity, an estimate of functional β-cell mass.Setting: The study was conducted at the Transplant Center and General Clinical Research Center of the University of Pennsylvania.Results: A 42-yr-old woman with type 1 diabetes who had a living-related kidney transplant received two intraportal islet infusions of a total 17,525 islet equivalents per kg body weight under daclizumab, prednisone, tacrolimus, and rapamycin immunosuppression. She became insulin independent, but 4 months later, the rapamycin was discontinued for associated colitis. She remained normoglycemic for another 6 months before manifesting impaired fasting glucose and requiring 5–10 U insulin daily. The decline in clinical islet graft function coincided with the detection of islet donor-specific human leukocyte antigen class I antibodies. β-Cell function and secretory capacity were assessed by the insulin secretory responses to iv glucose, arginine (AIRarg), and glucose-potentiated arginine (AIRpot) before and at alloantibody detection. The acute insulin response to glucose was almost entirely lost, whereas the AIRarg and AIRpot both decreased by approximately 50%.Conclusions: Because the AIRpot, a measure of β-cell secretory capacity, provides an estimate of functional β-cell mass, this case documents that islet graft loss can coincide with donor human leukocyte antigen sensitization and that the effect on β-cell mass may be best estimated from the AIRarg or AIRpot.
Postprandial Lipemia Associates with Liver Fat Content
Authors: Matikainen Niina , Mänttäri Sakari , Westerbacka Jukka , Vehkavaara Satu , Lundbom Nina , Yki-Järvinen Hannele , Taskinen Marja-Riitta 
Published: May 2007

AbstractContext/Objective: Postprandial lipemia and low adiponectin represent novel risk factors for vascular disease. This study aimed to determine whether liver fat content and adiponectin are predictors of postprandial triglyceride (TG)-rich lipoproteins (TRL).Patients/Interventions: Twenty-nine men were allocated into subgroups with either low (≤5%) or high (&gt;5%) liver fat measured with magnetic resonance proton spectroscopy. Subjects underwent an oral fat tolerance test with measurements of postprandial TG, cholesterol, apolipoprotein B-48 (apoB-48), and apoB-100 in TRL fractions, a euglycemic hyperinsulinemic clamp, and determination of abdominal fat volumes by magnetic resonance imaging.Results: Subjects with high liver fat displayed increased response of postprandial lipids in plasma, chylomicron, and very-low-density lipoprotein 1 (VLDL1) (Svedberg flotation rate 60–400) fractions. Liver fat correlated positively with postprandial responses (area under the curve) of TG (r = 0.597; P = 0.001), cholesterol (r = 0.546; P = 0.002), apoB-48 (r = 0.556; P = 0.002), and apoB-100 (r = 0.42; P = 0.023) in the VLDL1 fraction. Respective incremental areas under the curve correlated significantly with liver fat. Fasting adiponectin levels were inversely correlated with both postprandial lipids and liver fat content. Liver fat remained the only independent correlate in a multiple linear regression analysis for chylomicron and VLDL1 responses.Conclusions: Liver fat content is a close correlate of postprandial lipids predicting the responses of TRL in chylomicrons and VLDL1 better than measures of glucose metabolism or body adiposity. Low adiponectin concentration is closely linked to high liver fat content and impaired TRL metabolism. High liver fat content associated with postprandial lipemia represents potential risk factors for cardiovascular disease.
High coverage with HAART is required to substantially reduce the number of deaths from tuberculosis: system dynamics simulation
Authors: Atun Rifat A , Lebcir Reda M , Drobniewski Francis , McKee Martin , Coker Richard J 
Published: May 2007

We used a system dynamics simulation model of the transmission dynamics of drug-sensitive tuberculosis (DSTB), multidrug-resistant tuberculosis (MDRTB) and HIV to estimate the impact of coverage with highly active antiretroviral therapy (HAART) and different cure rates for MDRTB in settings of explosive HIV epidemics and high MDRTB levels. Population coverage levels at 0%, 25%, 50%, 75% and 100% for HAART, and 5% and 80% of MDRTB treatment cure rates were simulated over a 10-year period and cumulative deaths from tuberculosis and HIV-associated tuberculosis were estimated for populations with latent tuberculosis, DSTB, MDRTB, HIV and HIV-associated tuberculosis. Depending on levels of HAART population coverage, increasing MDRTB cure rates from 5% to 80% reduces cumulative tuberculosis deaths by 1% and 13%. High population coverage with HAART (75% or higher), allied with high MDRTB cure rates, reduces cumulative deaths by 60%, with limited impact below this level. High coverage with HAART is required to substantially reduce the number of deaths from tuberculosis.
Anaphylactic Shock Associated with Cefuroxime Axetil: Structure—Activity Relationships
Authors: Hasdenteufel Frédéric , Luyasu Samuel , Renaudin Jean-Marie , Trechot Philippe , Kanny Gisèle 
Published: May 2007

OBJECTIVE: To present a predictive model of allergenicity based on a structure– activity relationship analysis of β-lactam antibiotics using appropriate skin testing procedures. CASE SUMMARY: A 39-year-old woman was diagnosed with anaphylactic shock a few minutes after taking a 500 mg tablet cefuroxime of axetil and was admitted to the emergency department with dizziness, facial angioedema, generalized skin rash, and inferior cardiac ischemia. Skin testing confirmed the involvement of cefuroxime as the cause of the anaphylactic reaction, and the reaction was defined as probable according to the Naranjo probability scale. We then performed skin testing to study cross-reactivity between different β-lactam antibiotics. In addition to this initial assessment, a structure—activity relationship (SAR) analysis was done. It showed that the patient was sensitized to β-lactam antibiotics presenting a methoxyimino group, but not to similar compounds lacking this chemical group (eg, amoxicillin or penicillin G or V). Challenge with amoxicillin under intensive medical monitoring was tolerated up to a cumulated dose of 1 g, administered intravenously over 2 hours. DISCUSSION: This study demonstrates that SAR analysis could be useful to predict potential adverse reactions to related antibiotics and to select alternative strategies when antibiotic administration is essential. CONCLUSIONS: An SAR-based approach could help physicians and pharmacists provide allergic patients with relevant advice and propose viable alternatives regarding drug therapy.
Statistical analysis of the seasonal variation in the twinning rate
Authors: Fellman Johan , Eriksson Aldur W 
Published: May 2007

AbstractThere have been few secular analyses of the seasonal variation in human twinning and the results are conflicting. One reason for this is that the seasonal pattern of twinning varies in different populations and at different periods. Another reason is that the statistical methods used are different. The changing pattern of seasonal variation in twinning rates and total maternities in Denmark was traced for three periods (1855–69, 1870–94, and 1937–84). Two alternative methods of analysis are considered. The method of Walter and Elwood and a trigonometric regression model give closely similar results. The seasonal distribution of twin maternities for the periods in the 19th century showed highly significant departures. For both twin and general maternities, the main peaks can be seen from March to June and a local peak in September. During the spring– summer season the twinning rates were higher than the total birth rates, indicating a stronger seasonal variation for the twin maternities than for the general maternities. For 1937–84, there was a similar, but less accentuated, pattern. Studies of other populations are compared with the Danish results. The more accentuated seasonal variation of twinning in the past indicate that some factors in the past affected women during summer–autumn and around Christmas time, making them more fecund and particularly to be more prone to polyovulation and/or more able to complete a gestation with multiple embryos.
Genetics of early cancer detection behaviours in Australian female twins
Authors: Treloar Susan A , McDonald Christine A , Martin Nicholas G 
Published: May 2007

AbstractEarly detection of cervical and breast cancers is an important component of women's health strategy. Screening programmes, health professional interventions and preventive behaviours such as breast self-examination provide the means to this end. Our twin study sought to identify the relative influence of environmental and genetic factors on liability to early cancer detection behaviours, including use of cervical smear tests, mammograms, and breast examination. Additive genetic and random environmental effects models gave the best, most parsimonious fit to the data for each early cancer detection behaviour. The heritability of liability to Pap smear use was 66%, mammogram use 50%, breast examination by a doctor or nurse 38% and breast self-examination 37%. Genetic influences were behaviour-specific; there was no evidence for a common genetic influence on the four behaviours. Potential covariates investigated included age, amount of contact between co-twins, educational level and personality traits such as harm avoidance, novelty seeking, reward dependence, neuroticism, anxiety, depression, self-esteem, perceived control, interpersonal dependency and ways of coping. None were significant. The study was carried out before the implementation of national screening programmes with media campaigns to increase participation rates. Hence follow-up investigation, including data on regularity of behaviours, would be informative
A religious upbringing reduces the influence of genetic factors on disinhibition: Evidence for interaction between genotype and environment on personality
Authors: Boomsma DI , de Geus EJC , van Baal GCM , Koopmans JR 
Published: May 2007

AbstractInformation on personality, on anxiety and depression and on several aspects of religion was collected in 1974 Dutch families consisting of adolescent and young adult twins and their parents. Analyses of these data showed that differences between individuals in religious upbringing, in religious affiliation and in participation in church activities are not influenced by genetic factors. The familial resemblance for different aspects of religion is high, but can be explained entirely by environmental influences common to family members. Shared genes do not contribute to familial resemblances in religion. The absence of genetic influences on variation in several dimensions of religion is in contrast to findings of genetic influences on a large number of other traits that were studied in these twin families. Differences in religious background are associated with differences in personality, especially in Sensation Seeking. Subjects with a religious upbringing, who are currently religious and who engage in church activities score lower on the scales of the Sensation Seeking Questionnaire. The most pronounced effect is on the Disinhibition scale. The resemblances between twins for the Disinhibition scale differ according to their religious upbringing. Receiving a religious upbringing seems to reduce the influence of genetic factors on Disinhibition, especially in males.
Religion and depression: a review of the literature
Authors: McCullough Michael E , Larson David B 
Published: May 2007

AbstractWe reviewed data from approximately 80 published and unpublished studies that examined the association of religious affiliation or involvement with depressive symptoms or depressive disorder. In these studies, religion was measured as religious affiliation; general religious involvement; organizational religious involvement; prayer or private religious involvement; religious salience and motivation; or religious beliefs. People from some religious affiliations appear to have an elevated risk for depressive symptoms and depressive disorder, and people with no religious affiliation are at an elevated risk in comparison with people who are religiously affiliated. People with high levels of general religious involvement, organizational religious involvement, religious salience, and intrinsic religious motivation are at reduced risk for depressive symptoms and depressive disorders. Private religious activity and particular religious beliefs appear to bear no reliable relationship with depression. People with high levels of extrinsic religious motivation are at increased risk for depressive symptoms. Although these associations tend to be consistent, they are modest and are substantially reduced in multivariate research. Longitudinal research is sparse, but suggests that some forms of religious involvement might exert a protective effect against the incidence and persistence of depressive symptoms or disorders. The existing research is sufficient to encourage further investigation of the associations of religion with depressive symptoms and disorder. Religion should be measured with higher methodological standards than those that have been accepted in survey research to date.
Resiliency factors protecting against teenage alcohol use and smoking: influences of religion, religious involvement and values, and ethnicity in the Missouri Adolescent Female Twin Study
Authors: Heath AC , Madden PAF , Grant JD , McLaughlin TL , Todorov AA , Bucholz KK 
Published: May 2007

AbstractThe objective of this study was to investigate the contribution of ethnicity (African American vs European/other ancestry), family religious affiliation, religious involvement, and religious values, to risk of alcohol and cigarette use in adolescent girls; and to estimate genetic and shared environmental effects on religious involvement and values. Telephone interviews were conducted with a sample of female like-sex twin pairs, aged 13–20 (n = 1687 pairs, including 220 minority pairs), as well as with one or both parents of twins aged 11–20 (n = 2111 families). These data, together with one-year follow-up twin questionnaire data, and two-year follow-up parent interview data, were used to compare ethnic differences. Proportional hazards regression models and genetic variance component models were fitted to the data. Despite higher levels of exposure to family, school and neighborhood environmental adversities, African American adolescents were less likely to become teenage drinkers or smokers. They showed greater religious involvement (frequency of attendance at religious services) and stronger religious values (eg belief in relying upon their religious beliefs to guide day-to-day living). Controlling for religious affiliation, involvement and values removed the ethnic difference in alcohol use, but had no effect on the difference in rates of smoking. Religious involvement and values exhibited high heritability in African Americans, but only modest heritability in EOAs. The strong protective effect of adolescent religious involvement and values, and its contribution to lower rates of African American alcohol use, was confirmed. We speculate about the possible association between high heritability of African American religious behavior and an accelerated maturation of religious values during adolescence.