bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders
Authors: Yamasaki Nobuyuki , Maekawa Motoko , Kobayashi Katsunori , Kajii Yasushi , Maeda Jun , Soma Miho , Takao Keizo , Tanda Koichi , Ohira Koji , Toyama Keiko , Kanzaki Kouji , Fukunaga Kohji , Sudo Yusuke , Ichinose Hiroshi , Ikeda Masashi , Iwata Nakao , Ozaki Norio , Suzuki Hidenori , Higuchi Makoto , Suhara Tetsuya , Yuasa Shigeki , Miyakawa Tsuyoshi 
Published: September 2008

AbstractElucidating the neural and genetic factors underlying psychiatric illness is hampered by current methods of clinical diagnosis. The identification and investigation of clinical endophenotypes may be one solution, but represents a considerable challenge in human subjects. Here we report that mice heterozygous for a null mutation of the alpha-isoform of calcium/calmodulin-dependent protein kinase II (alpha-CaMKII+/-) have profoundly dysregulated behaviours and impaired neuronal development in the dentate gyrus (DG). The behavioral abnormalities include a severe working memory deficit and an exaggerated infradian rhythm, which are similar to symptoms seen in schizophrenia, bipolar mood disorder and other psychiatric disorders. Transcriptome analysis of the hippocampus of these mutants revealed that the expression levels of more than 2000 genes were significantly changed. Strikingly, among the 20 most downregulated genes, 5 had highly selective expression in the DG. Whereas BrdU incorporated cells in the mutant mouse DG was increased by more than 50 percent, the number of mature neurons in the DG was dramatically decreased. Morphological and physiological features of the DG neurons in the mutants were strikingly similar to those of immature DG neurons in normal rodents. Moreover, c-Fos expression in the DG after electric footshock was almost completely and selectively abolished in the mutants. Statistical clustering of human post-mortem brains using 10 genes differentially-expressed in the mutant mice were used to classify individuals into two clusters, one of which contained 16 of 18 schizophrenic patients. Nearly half of the differentially-expressed probes in the schizophrenia-enriched cluster encoded genes that are involved in neurogenesis or in neuronal migration/maturation, including calbindin, a marker for mature DG neurons. Based on these results, we propose that an "immature DG" in adulthood might induce alterations in behavior and serve as a promising candidate endophenotype of schizophrenia and other human psychiatric disorders.
Characterization, Expression, and Functional Activity of Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors in Human Granulosa-Luteal Cells
Authors: Morelli Maria Beatrice , Barberi Marzia , Gambardella Alessia , Borini Andrea , Cecconi Sandra , Coticchio Giovanni , Canipari Rita 
Published: September 2008

Context: Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are found in the ovary of mammalian species, although nothing is known about the possible role of PACAP and VIP in the human ovary.
Objective: We investigated the expression of PACAP and PACAP/VIP receptors in human granulosa-luteal (GL) cells obtained from consenting in vitro fertilization patients attending a private fertility clinic and assessed a possible antiapoptotic effect of these molecules.
Main Outcome Measures: We measured the expression of PACAP and PACAP/VIP receptor mRNAs in GL cells in response to FSH or LH, as well as the effects of PACAP and VIP on apoptosis. We also evaluated the levels of procaspase-3 in GL cells cultured in the absence of serum.
Results: After 7 d in culture, GL cells displayed increased responsiveness to FSH and LH (100 ng/ml). FSH and LH promoted PACAP expression, LH doing so in a time-dependent fashion. VIP receptor (VPAC1-R and VPAC2-R) mRNAs were also induced by gonadotropin stimulation. Although PACAP receptor (PAC1-R) mRNA was barely detectable, Western blot analysis revealed its presence. The apoptotic effect of serum withdrawal from the culture environment was reverted by both PACAP and VIP. Both peptides showed the ability to reverse a decrease in procaspase-3 levels induced by culture in the absence of serum.
Conclusions: PACAP and VIP appear to play a role in maintenance of follicle viability as a consequence of the antiapoptotic effect. Further studies are warranted to evaluate the respective roles of PACAP and VIP in ovarian physiology and to identify their mechanism of action.
Effects of Continuous Versus Intermittent Exercise, Obesity, and Gender on Growth Hormone Secretion
Authors: Weltman Arthur , Weltman Judy Y. , Watson Winfield Dee Dee , Frick Kirsten , Patrie James , Kok Petra , Keenan Daniel M. , Gaesser Glenn A. , Veldhuis Johannes D. 
Published: September 2008

Context: Obesity attenuates spontaneous GH secretion and the GH response to exercise. Obese individuals often have low fitness levels, limiting their ability to complete a typical 30-min bout of continuous exercise. An alternative regimen in obese subjects may be shorter bouts of exercise interspersed throughout the day.
Objective: The objective of the study was to examine whether intermittent and continuous exercise interventions evoke similar patterns of 24-h GH secretion and whether responses are attenuated in obese subjects or affected by gender.
Design: This was a repeated-measures design in which each subject served as their own control.
Setting: This study was conducted at the University of Virginia General Clinical Research Center.
Subjects: Subjects were healthy nonobese (n = 15) and obese (n = 14) young adults.
Interventions: Subjects were studied over 24 h at the General Clinical Research Center on three occasions: control, one 30-min bout of exercise, and three 10-min bouts of exercise.
Main Outcome Measures: Twenty-four hour GH secretion was measured.
Results: Compared with unstimulated 24-h GH secretion, both intermittent and continuous exercise, at constant exercise intensity, resulted in severalfold elevation of 24-h integrated serum GH concentrations in young adults. Basal and pulsatile modes of GH secretion were attenuated both at rest and during exercise in obese subjects.
Conclusions: The present data suggest that continuous and intermittent exercise training should be comparably effective in increasing 24-h GH secretion.
Longitudinal Analysis of the Insulin-Like Growth Factor System in African-American and European American Children and Adolescents
Authors: Casazza Krista , Higgins Paul B. , Fernández José R. , Goran Michael I. , Gower Barbara A. 
Published: September 2008

Context: IGF-I and its binding proteins influence growth, development, and disease risk. Studies have revealed ethnic variations in the IGF system.Objective: This longitudinal study was undertaken to test the hypothesis that the ethnic differences in the IGF system exist throughout the pubertal transition, and these differences are mediated at least in part by inherent differences in insulin dynamics.Design: This was a longitudinal study. Annual evaluations were conducted for pubertal maturation, body composition, acute insulin response to glucose (AIRg), and reproductive-endocrine profile. Hormones and binding proteins were determined using standard assays, the AIRg during a frequently sampled iv glucose tolerance test, and body composition by dual-energy x-ray absorptiometry. Mixed model analyses were used to identify and characterize ethnic differences in the IGF system across the pubertal transition after adjusting for ethnicity, sex, age, maturation status, body composition, and reproductive hormones, and to identify the contribution of insulin to IGF binding protein (IGFBP)-1.Participants: Subjects included African-American (AA) and European American children (n = 162 at baseline) aged 7–16 yr, evaluated across the pubertal transition.Main Outcome Measures: Annual data on IGF-I, IGFBP-1, and IGFBP-3 were examined.Results: IGF-I was higher in AA children at pubertal stage 1 only (P &lt; 0.001). However, IGFBP-3 and IGFBP-1 concentrations were lower in AAs through much of puberty (P &lt; 0.05). The lower IGFBP-1 of AAs was in part explained by greater AIRg.Conclusions: Our data suggest that the higher IGF-I and lower IGFBP-1 and IGFBP-3 levels in AAs as compared with European Americans during puberty suggest potential ethnic differences in circulating bioavailable IGF-I. In addition, higher AIRg in AAs may lead to greater bioavailable IGF-I. Whether these differences in the IGF system account for disparities in disease risk warrants further investigation.
Plasma Lecithin: Cholesterol Acyltransferase Activity Is Elevated in Metabolic Syndrome and Is an Independent Marker of Increased Carotid Artery Intima Media Thickness
Authors: Dullaart Robin P. F. , Perton Frank , Sluiter Wim J. , de Vries Rindert , van Tol Arie 
Published: September 2008

Context: Lecithin:cholesterol acyltransferase (LCAT), which esterifies free cholesterol to cholesteryl esters, is required for normal plasma lipoprotein structure and is instrumental in high density lipoprotein (HDL) remodeling, but the relationship of variation in plasma LCAT activity with subclinical atherosclerosis is unclear.Objectives: The aim of the study was to determine the effect of the metabolic syndrome (MetS) on plasma LCAT activity and its relationship with carotid artery intima media thickness (IMT).Setting: The study was conducted at the vascular laboratory of a university medical center.Methods: In 74 subjects with MetS and 90 subjects without MetS (National Cholesterol Education Program Adult Treatment Panel III criteria), mean carotid artery IMT, plasma lipids, LCAT activity (exogenous substrate method), high-sensitive C-reactive protein, and homeostasis model assessment insulin resistance (HOMAir) were documented.Results: IMT was greater (P = 0.01) and plasma LCAT activity was higher (P &lt; 0.001) in subjects with MetS compared to subjects without MetS. Similar increases in IMT and LCAT were found in MetS subjects without type 2 diabetes mellitus. Multiple linear regression analysis demonstrated that plasma LCAT activity was independently and positively related to HOMAir, plasma triglycerides, non-HDL cholesterol, and HDL cholesterol (all P &lt; 0.001). After adjustment for age and sex, IMT was positively associated with LCAT activity (P &lt; 0.01), independently of the presence of MetS (or alternatively of plasma lipids), HOMAir, and high-sensitive C-reactive protein.Conclusions: Plasma LCAT activity is elevated in MetS and may be a marker of subclinical atherosclerosis. Our findings do not support the contention that strategies to elevate LCAT are necessarily beneficial for cardioprotection.
The Genetics of Type 2 Diabetes: A Realistic Appraisal in 2008
Authors: Florez Jose C. 
Published: September 2008

Context: Over the last few months, genome-wide association studies have contributed significantly to our understanding of the genetic architecture of type 2 diabetes. If and how this information will impact clinical practice is not yet clear.
Evidence Acquisition: Primary papers reporting genome-wide association studies in type 2 diabetes or establishing a reproducible association for specific candidate genes were compiled. Further information was obtained from background articles, authoritative reviews, and relevant meeting conferences and abstracts.
Evidence Synthesis: As many as 17 genetic loci have been convincingly associated with type 2 diabetes; 14 of these were not previously known, and most of them were unsuspected. The associated polymorphisms are common in populations of European descent but have modest effects on risk. These loci highlight new areas for biological exploration and allow the initiation of experiments designed to develop prediction models and test possible pharmacogenetic and other applications.
Conclusions: Although substantial progress in our knowledge of the genetic basis of type 2 diabetes is taking place, these new discoveries represent but a small proportion of the genetic variation underlying the susceptibility to this disorder. Major work is still required to identify the causal variants, test their role in disease prediction and ascertain their therapeutic implications.
Medication Reconciliation at Hospital Discharge: Evaluating Discrepancies
Authors: Wong Jacqueline D , Bajcar Jana M , Wong Gary G , Alibhai Shabbir MH , Huh Jin-Hyeun , Cesta Annemarie , Pond Gregory R , Fernandes Olavo A 
Published: September 2008

Background: Hospital discharge is an interlace of care when patients are at a high risk of medication discrepancies as they transition from hospital to home. These discrepancies are important, as they may contribute to drug-related problems, medication errors, and adverse drug events. Objective: To Identify, characterize, and assess the clinical impact of unintentional medication discrepancies at hospital discharge. Methods: All consecutive general internal medicine patients admitted for at least 72 hours to a tertiary care teaching hospital were prospectively assessed. Patients were excluded if they were discharged with verbal prescriptions; died during hospitalization; or transferred from or to a nursing home, another institution, or another unit within the same hospital. The primary endpoint was to determine the number of patients with at least one unintended medication discrepancy on hospital discharge. Medication discrepancies were assessed through comparison of a best possible medication discharge list with the actual discharge prescriptions. Secondary objectives were to characterize and assess the potential clinical impact of the unintentional discrepancies. Results: From March 14,2006, to June 2,2006,430 patients were screened for eligibility; 150 patients were included in the study. Overall, 106 (70.7%) patients had at least one actual or potential unintentional discrepancy. Sixty-two patients (41.3%) had at least one actual unintentional medication discrepancy al hospital discharge and 83 patients (55.3%) had at least one potential unintentional discrepancy. The most common unintentional discrepancies were an incomplete prescription requiring clarification, which could result in a patient delay in obtaining medications (49.5%), and the omission of medications (22.9%). Of the 105 unintentional discrepancies, 31 (29.5%) had the potential to cause possible or probable patient discomfort and/or clinical deterioration. Conclusions: Medication discrepancies occur commonly on hospital discharge. Understanding the type and frequency of discrepancies can help clinicians better understand ways to prevent them. Structured medication reconciliation may help to prevent discharge medication discrepancies.
Communication prompts donation: Exploring the beliefs underlying registration and discussion of the organ donation decision
Authors: Hyde Melissa K. , White Katherine M. 
Published: September 2008

Objectives. To use a theory of planned behaviour (TPB) framework to explore the beliefs underlying communication of the donation decision for people who had not previously registered their consent on a donor register or discussed their decision with significant others.Design. Initially, a focus group study elicited the common TPB (behavioural, normative, and control) beliefs about registering and discussing the organ donation decision. The main study assessed the important TPB belief predictors of intentions to register and discuss the donation decision.Method. University students and community members from Queensland, Australia (N = 123) completed items assessing their intentions and the TPB behavioural, normative, and control beliefs for registering and discussing their donation decision.Results. Structural equation modelling (SEM) analyses revealed significant paths between people's intentions to register their donation decisions and underlying behavioural (e.g. enabling efficient donation procedures), normative (e.g. friends, doctors/medical professionals), and control (e.g. lack of motivation, knowing details about transplant recipients) beliefs (R2=.30). There were also significant paths between people's intentions to discuss their donation decision and underlying behavioural (e.g. feeling uncomfortable talking about death related topics) and normative (e.g. partner/spouse, family members) beliefs, but not control beliefs (R2=.33). There was a significant path between intentions to register and intentions to discuss one's donation decision.Conclusions. Results highlight the importance of focusing on behavioural and normative beliefs about communicating the donation decision, specifically for people who have not previously communicated their decision, and suggest potential targets for interventions designed to promote decision communication.
Positive Selection at the Binding Sites of the Male-Specific Lethal Complex Involved in Dosage Compensation in Drosophila
Authors: Bachtrog Doris 
Published: September 2008

AbstractIn many taxa, males and females differ with respect to their sex chromosomes, and dosage compensation mechanisms have evolved to equalize X-linked gene transcription. In Drosophila, the male-specific lethal (MSL) complex binds to hundreds of sites along the male X chromosome and mediates twofold hypertranscription of the single male X. Two recent studies found evidence for lineage-specific adaptive evolution in all five core protein-coding genes of the MSL complex in Drosophila melanogaster. In particular, dramatic positive selection was detected in domains shown to be responsible for their specific targeting to the X chromosome. Here I use population genetics to show that three previously characterized MSL-binding DNA segments on the X themselves underwent adaptive evolution in D. melanogaster, but not in its close relatives D. simulans and D. yakuba. MSL components have been shown to not correctly target the D. melanogaster X chromosome in hybrids between D. melanogaster and D. simulans. My finding supports the idea of selection-driven coevolution among DNA-protein interactions of the dosage compensation machinery and suggests that misregulated dosage compensation could contribute to male hybrid inviability in Drosophila.
A Two-Stage Pruning Algorithm for Likelihood Computation for a Population Tree
Authors: RoyChoudhury Arindam , Felsenstein Joseph , Thompson Elizabeth A 
Published: September 2008

AbstractWe have developed a pruning algorithm for likelihood estimation of a tree of populations. This algorithm enables us to compute the likelihood for large trees. Thus, it gives an efficient way of obtaining the maximum-likelihood estimate (MLE) for a given tree topology. Our method utilizes the differences accumulated by random genetic drift in allele count data from single-nucleotide polymorphisms (SNPs), ignoring the effect of mutation after divergence from the common ancestral population. The computation of the maximum-likelihood tree involves both maximizing likelihood over branch lengths of a given topology and comparing the maximum-likelihood across topologies. Here our focus is the maximization of likelihood over branch lengths of a given topology. The pruning algorithm computes arrays of probabilities at the root of the tree from the data at the tips of the tree; at the root, the arrays determine the likelihood. The arrays consist of probabilities related to the number of coalescences and allele counts for the partially coalesced lineages. Computing these probabilities requires an unusual two-stage algorithm. Our computation is exact and avoids time-consuming Monte Carlo methods. We can also correct for ascertainment bias.
AMBIENCE: A Novel Approach and Efficient Algorithm for Identifying Informative Genetic and Environmental Associations With Complex Phenotypes
Authors: Chanda Pritam , Sucheston Lara , Zhang Aidong , Brazeau Daniel , Freudenheim Jo L , Ambrosone Christine , Ramanathan Murali 
Published: September 2008

AbstractWe developed a computationally efficient algorithm AMBIENCE, for identifying the informative variables involved in gene–gene (GGI) and gene–environment interactions (GEI) that are associated with disease phenotypes. The AMBIENCE algorithm uses a novel information theoretic metric called phenotype-associated information (PAI) to search for combinations of genetic variants and environmental variables associated with the disease phenotype. The PAI-based AMBIENCE algorithm effectively and efficiently detected GEI in simulated data sets of varying size and complexity, including the 10K simulated rheumatoid arthritis data set from Genetic Analysis Workshop 15. The method was also successfully used to detect GGI in a Crohn's disease data set. The performance of the AMBIENCE algorithm was compared to the multifactor dimensionality reduction (MDR), generalized MDR (GMDR), and pedigree disequilibrium test (PDT) methods. Furthermore, we assessed the computational speed of AMBIENCE for detecting GGI and GEI for data sets varying in size from 100 to 105 variables. Our results demonstrate that the AMBIENCE information theoretic algorithm is useful for analyzing a diverse range of epidemiologic data sets containing evidence for GGI and GEI.
Selection at Work in Self-Incompatible Arabidopsis lyrata. II. Spatial Distribution of S Haplotypes in Iceland
Authors: Schierup Mikkel H , Bechsgaard Jesper S , Christiansen Freddy B 
Published: September 2008

Abstract
We survey the distribution of haplotypes at the self-incompatibility (SI) locus of Arabidopsis lyrata (Brassicaceae) at 12 locations spread over the species' natural distribution in Iceland. Previous investigations of the system have identified 34 functionally different S haplotypes maintained by frequency-dependent selection and arranged them into four classes of dominance in their phenotypic expression. On the basis of this model of dominance and the island model of population subdivision, we compare the distribution of S haplotypes with that expected from population genetic theory. We observe 18 different S haplotypes, recessive haplotypes being more common than dominant ones, and dominant ones being shared by fewer populations. As expected, differentiation, although significant, is very low at the S locus even over distances of up to 300 km. The frequency of the most recessive haplotype is slightly larger than expected for a panmictic population, but consistent with a subdivided population with the observed differentiation. Frequencies in nature reflect effects of segregation distortion previously observed in controlled crosses. The dynamics of the S-locus variation are, however, well represented by a 12-island model and our simplified model of dominance interactions.
Patterns of Molecular Evolution Associated With Two Selective Sweeps in the Tb1–Dwarf8 Region in Maize
Authors: Camus-Kulandaivelu Letizia , Chevin Luis-Miguel , Tollon-Cordet Christine , Charcosset Alain , Manicacci Domenica , Tenaillon Maud I 
Published: September 2008

Abstract
We focused on a region encompassing a major maize domestication locus, Tb1, and a locus involved in the flowering time variation, Dwarf8 (D8), to investigate the consequences of two closely linked selective sweeps on nucleotide variation and gain some insights into maize geographical diffusion, through climate adaptation. First, we physically mapped D8 at ∼300 kb 3′ of Tb1. Second, we analyzed patterns of nucleotide variation at Tb1, D8, and seven short regions (400–700 bp) located in the Tb1–D8 region sequenced on a 40 maize inbred lines panel encompassing early-flowering temperate and late-flowering tropical lines. The pattern of polymorphism along the region is characterized by two valleys of depleted polymorphism while the region in between exhibits an appreciable amount of diversity. Our results reveal that a region ∼100 kb upstream of the D8 gene exhibits hallmarks of divergent selection between temperate and tropical lines and is likely closer than the D8 gene to the target of selection for climate adaptation. Selection in the tropical lines appears more recent than in the temperate lines, suggesting an initial domestication of early-flowering maize. Simulation results indicate that the polymorphism pattern is consistent with two interfering selective sweeps at Tb1 and D8.