bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjunctive Aripiprazole in Bipolar I Depression
Authors: Sokolski Kenneth N 
Published: December 2006

Background: Aripiprazole has demonstrated efficacy in treatment of bipolar mania, as well as in the maintenance treatment of bipolar disorder. There has been only one report supporting a role for this agent in the depressed phase of the illness. Objective: To evaluate the effectiveness of adjunctive aripiprazole in bipolar I depressed patients who are nonresponders to standard therapy. Methods: Chart records were reviewed for all patients with bipolar I depression, diagnosed by Diagnostic and Statistical Manual of Mental Disorders, 4th revision, criteria between June 2004 and January 2006 from the Long Beach Veterans Affairs Mood Disorders Clinic. Included subjects had experienced moderate to marked depressive symptoms (Clinical Global Impression–Bipolar Depression ≥4) despite at least 2 months of treatment with adequate doses of at least one mood stabilizer. In addition, all subjects had been treated subsequently with aripiprazole 15–30 mg/day added to the existing regimen. Detailed chart notes were used to retrospectively rate symptoms. The presence or absence of each symptom was recorded before and after aripiprazole augmentation. Based on these data, Clinical Global Impression bipolar severity (CGI-BP-S) ratings and CGI-BP improvement scores for bipolar I depression were assigned. Results: Ten subjects met study criteria. Adjunctive aripiprazole given for 21–110 days resulted in significant improvements in CGI-BP-S depression ratings. Seven of 10 patients were assigned CGI-BP improvement ratings of much or very much improved. Adverse events were mild and included akathisia, nausea, and insomnia. Dose adjustments of aripiprazole or the addition of drugs to treat adverse effects excluded subjects from further data collection. No patient stopped aripiprazole due to adverse effects. Conclusions: This study adds to a previous report indicating beneficial effects of adjunctive aripiprazole in treatment of bipolar I depression. Double-blind, placebo-controlled investigations are needed to confirm these findings.
The Role of Olanzapine in the Treatment of Anorexia Nervosa
Authors: Dunican Kaelen C , DelDotto Dana 
Published: December 2006

Objective: To evaluate the role of olanzapine in the treatment of anorexia nervosa. Data Sources: Literature was obtained through searches of MEDLINE (1966–December 2006), EMBASE (1980–4th Quarter 2006), and PsycINFO (1985–December 2006) and a bibliographic review of published articles. Key terms used in the searches included anorexia nervosa, antipsychotics, eating disorders, olanzapine, and Zyprexa. Study Selection And Data Extraction: All English language articles that were identified from the search were evaluated. All primary literature was included in the review. Data Synthesis: In several case reports and most clinical trials, patients with anorexia nervosa successfully gained weight while being treated with olanzapine. Moreover, many patients treated with olanzapine achieved a healthy body weight. Case reports and trials identified additional benefits of olanzapine, including reduction in delusional thinking; improvement in body image, sleep, depressive symptoms, adherence to treatment, and eating-disorder symptoms; and decreased agitation and premeal anxiety. Conclusions: Preliminary evidence supports the use of olanzapine for treatment of anorexia nervosa by demonstrating that olanzapine 2.5–15 mg daily promotes weight gain and has positive effects on associated psychological symptoms. Limitations of the reported data include small sample size, low completion rate in clinical trials, and open-label trial design. Although olanzapine appears to have a potential role in the treatment of anorexia nervosa that has been unresponsive to other therapy, randomized, placebo-controlled studies with larger sample sizes are necessary to establish its role in therapy.
Livedoid Skin Reaction Probably Due to Imatinib Therapy
Authors: Martínez-González M Covadonga , Pozo Jesús del , Yebra-Pimentel María Teresa , Pérez Mónica , Almagro Manuel , Fonseca Eduardo 
Published: December 2006

Objective: To report 3 cases of skin rash with a peculiar livedoid pattern that were probably associated with imatinib therapy. Case Summary: In the first case, a 74-year-old male diagnosed with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML), treated with imatinib 400 mg/day, developed a skin eruption with a livedoid pattern. Systemic corticosteroids were started, and skin lesions improved. The second case involved a 66-year-old male with Ph+ CML who was treated with imatinib 600 mg/day. After initiation of this treatment, he developed a skin rash with a livedoid pattern. The drug treatment was discontinued and then reintroduced. Topical corticosteroid treatment was started, resulting in total remission of the skin lesions. When the imatinib dose was progressively reintroduced, the skin lesions recurred. The patient died as a result of the progression of his disease. In the third case, a 43-year-old male with Ph+ acute lymphoblastic leukemia was treated with imatinib 600 mg/day. After a few days of treatment, the patient developed a skin rash with a livedoid pattern. He died as a result of probable septic shock. Discussion: Imatinib is a tyrosine kinase receptor inhibitor that inhibits BCR/ABL tyrosine kinase. There have been several published articles on cutaneous adverse reactions related to imatinib therapy. The most common cutaneous adverse event of imatinib is a rash with variable clinical presentation. The Naranjo probability scale indicated a probable relationship between imatinib and the rash in all 3 cases reported hero. Conclusions: Adverse reactions to imatinib that affect the skin occur frequently. They are strongly dose dependent, self-limiting, or easily managed by lowering the dose of imatinib and, if necessary, prescribing short-term therapy with a systemic corticosteroid. Clinicians should monitor patients taking imatinib and institute treatment quickly if a rash develops.
N-Acetylcysteine and Sodium Bicarbonate Versus N-Acetylcysteine and Standard Hydration for the Prevention of Radiocontrast-Induced Nephropathy Following Coronary Angiography
Authors: Schmidt Paul , Pang Dorothy , Nykamp Diane , Knowlton Gregory , Jia Haomiao 
Published: December 2006

Background: Radiocontrast-induced nephropathy (RCIN) is thought to be caused by renal ischemia and direct toxic effects on renal tubular cells brought on by contrast media. The combination of N-acetylcysteine (NAC) and hydration fluids (NaCI 0.9% or 0.45%) has been shown to reduce these deleterious effects and is commonly given prior to coronary angiography. The use of bicarbonate as the hydration anion has been shown to confer additional RCIN protection compared with that of saline. However, limited data are available regarding whether sodium bicarbonate hydration, proven to be beneficial alone, can further improve outcomes when given with NAC. Objective: To compare the incidence of RCIN in patients undergoing coronary angiography after pretreatment with NAC plus sodium bicarbonate hydration or NAC plus standard hydration (NaCI 0.9% or 0.45%). Methods: A retrospective, single-center study evaluated 96 patients who underwent coronary angiography from January 2002 to December 2005. Data were collected through electronic chart reviews. Results: Forty-seven patients received NAC and sodium bicarbonate for hydration and 49 received NAC and standard hydration. Baseline characteristics between the 2 groups were similar. All patients received at least one 600 mg oral dose of NAC before angiography was performed. RCIN was defined as impairment of renal function occurring within 72 hours of administering contrast media, indicated by an absolute increase in the serum creatinine level of 0.5 mg/dL or more. A total of 12.2% of the patients receiving NAC and standard hydration developed RCIN, versus 14.9% of the patients in the NAC and sodium bicarbonate group (p = 0.713). Conclusions: The addition of sodium bicarbonate to NAC does not appear to confer additional protection against the development of RCIN. Prospective, randomized, placebo-controlled trials are warranted to definitively determine how this combination compares with NAC and standard hydration in preventing RCIN.
Diabetes: Rationale for Dipeptidyl Peptidase 4 Inhibitors: A New Class of Oral Agents for the Treatment of Type 2 Diabetes Mellitus
Authors: Campbell R Keith 
Published: December 2006

Objective: To review advances in understanding the pathophysiologic basis of type 2 diabetes mellitus and the pharmacology and mechanism of action of dipeptidyl peptidase 4 (DPP-4) inhibition in correcting the underlying defects in glycemic control. Data Sources: Articles were identified through MEDLINE for the period 1966 through November 2006. Abstracts and presentations from the American Diabetes Association Scientific Sessions and the European Association for the Study of Diabetes (2002–2006) were also searched for scientific reports on DPP-4 inhibitors. Study Selection And Data Extraction: Abstracts, original clinical and preclinical research reports, and review articles published in the English language were identified for review. Literature discussing glucose regulation, incretin hormones, type 2 diabetes pathophysiology, and DPP-4 inhibition were evaluated and selected based on consideration of their support for the proof of concept, mechanistic and in vivo findings, and timeliness. Data Synthesis: The search for new and effective therapies for type 2 diabetes has led to the identification of a novel therapeutic target, the incretin hormones, which play a role in mediating glucose homeostasis via effects on glucagon and insulin secretion from pancreatic islet α- and β-cells, respectively. The incretins' glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide are rapidly inactivated by the enzyme DPP-4. DPP-4 inhibitor agents act by blocking the active site of DPP-4, thereby preventing inactivation of and prolonging the duration of action of incretins, which in turn helps to correct the defective insulin and glucagon secretion that marks type 2 diabetes. Clinical studies to date indicate that DPP-4 inhibitors effectively stimulate insulin secretion, suppress glucagon release, and improve glucose control in patients with type 2 diabetes. These agents are well tolerated and have a low incidence of adverse effects. Conclusions: The DPP-4 inhibitors are novel agents for the treatment of type 2 diabetes. Compounds under development in this new class of oral antidiabetic drugs may be free of the limitations of current therapies.
An Extension of the Transmission Disequilibrium Test Incorporating Imprinting
Authors: Hu Yue-Qing , Zhou Ji-Yuan , Fung Wing K 
Published: December 2006

Abstract
The recombination rates in meioses of females and males are often different. Some genes that affect development and behavior in mammals are known to be imprinted, and &gt;1% of all mammalian genes are believed to be imprinted. When the gene is imprinted and the recombination fractions are sex specific, the conventional transmission disequilibrium test (TDT) is shown to be still valid for testing for linkage. The power function of the TDT is derived, and the effect of the degree of imprinting on the power of the TDT is investigated. It is learned that imprinting has little effect on the power when the female and male recombination rates are equal. On the basis of case–parents trios, the transmissions from the heterozygous fathers/mothers to their affected children are separated as paternal and maternal, and two TDT-like statistics, TDTp and TDTm, are consequently constructed. It is found that the TDTp possesses a higher power than the TDT for maternal imprinting genes, and the TDTm is more powerful than the TDT for paternal imprinting genes. On the basis of the parent-of-origin effects test statistic (POET), a novel statistic, TDT incorporating imprinting (TDTI) is proposed to test for linkage in the presence of linkage disequilibrium, which is shown to be more powerful than the TDT when parent-of-origin effects are significant but slightly less powerful than the TDT when parent-of-origin effects are negligible. The validity of the TDT and TDTI is assessed by simulation. The power approximation formulas for the TDT and TDTI are derived and the simulation results show that they are accurate. The simulation study on power comparison shows that the TDTI outperforms the TDT for imprinted genes. The improvement can be substantial in the case of complete paternal/maternal imprinting.
The Structure of Linkage Disequilibrium Around a Selective Sweep
Authors: McVean Gil 
Published: December 2006

Abstract
The fixation of advantageous mutations by natural selection has a profound impact on patterns of linked neutral variation. While it has long been appreciated that such selective sweeps influence the frequency spectrum of nearby polymorphism, it has only recently become clear that they also have dramatic effects on local linkage disequilibrium. By extending previous results on the relationship between genealogical structure and linkage disequilibrium, I obtain simple expressions for the influence of a selective sweep on patterns of allelic association. I show that sweeps can increase, decrease, or even eliminate linkage disequilibrium (LD) entirely depending on the relative position of the selected and neutral loci. I also show the importance of the age of the neutral mutations in predicting their degree of association and describe the consequences of such results for the interpretation of empirical data. In particular, I demonstrate that while selective sweeps can eliminate LD, they generate patterns of genetic variation very different from those expected from recombination hotspots.
Rmd9p Controls the Processing/Stability of Mitochondrial mRNAs and Its Overexpression Compensates for a Partial Deficiency of Oxa1p in Saccharomyces cerevisiae
Authors: Nouet Cécile , Bourens Myriam , Hlavacek Otakar , Marsy Sophie , Lemaire Claire , Dujardin Geneviève 
Published: December 2006

Abstract
Oxa1p is a key component of the general membrane insertion machinery of eukaryotic respiratory complex subunits encoded by the mitochondrial genome. In this study, we have generated a respiratory-deficient mutant, oxa1-E65G-F229S, that contains two substitutions in the predicted intermembrane space domain of Oxa1p. The respiratory deficiency due to this mutation is compensated for by overexpressing RMD9. We show that Rmd9p is an extrinsic membrane protein facing the matrix side of the mitochondrial inner membrane. Its deletion leads to a pleiotropic effect on respiratory complex biogenesis. The steady-state level of all the mitochondrial mRNAs encoding respiratory complex subunits is strongly reduced in the Δrmd9 mutant, and there is a slight decrease in the accumulation of two RNAs encoding components of the small subunit of the mitochondrial ribosome. Overexpressing RMD9 leads to an increase in the steady-state level of mitochondrial RNAs, and we discuss how this increase could suppress the oxa1 mutations and compensate for the membrane insertion defect of the subunits encoded by these mRNAs.
Genetic Dissection of Ethanol Tolerance in the Budding Yeast Saccharomyces cerevisiae
Authors: Hu X H , Wang M H , Tan T , Li J R , Yang H , Leach L , Zhang R M , Luo Z W 
Published: December 2006

Abstract
Uncovering genetic control of variation in ethanol tolerance in natural populations of yeast Saccharomyces cerevisiae is essential for understanding the evolution of fermentation, the dominant lifestyle of the species, and for improving efficiency of selection for strains with high ethanol tolerance, a character of great economic value for the brewing and biofuel industries. To date, as many as 251 genes have been predicted to be involved in influencing this character. Candidacy of these genes was determined from a tested phenotypic effect following gene knockout, from an induced change in gene function under an ethanol stress condition, or by mutagenesis. This article represents the first genomics approach for dissecting genetic variation in ethanol tolerance between two yeast strains with a highly divergent trait phenotype. We developed a simple but reliable experimental protocol for scoring the phenotype and a set of STR/SNP markers evenly covering the whole genome. We created a mapping population comprising 319 segregants from crossing the parental strains. On the basis of the data sets, we find that the tolerance trait has a high heritability and that additive genetic variance dominates genetic variation of the trait. Segregation at five QTL detected has explained ∼50% of phenotypic variation; in particular, the major QTL mapped on yeast chromosome 9 has accounted for a quarter of the phenotypic variation. We integrated the QTL analysis with the predicted candidacy of ethanol resistance genes and found that only a few of these candidates fall in the QTL regions.
Background Selection in Single Genes May Explain Patterns of Codon Bias
Authors: Loewe Laurence , Charlesworth Brian 
Published: December 2006

AbstractBackground selection involves the reduction in effective population size caused by the removal of recurrent deleterious mutations from a population. Previous work has examined this process for large genomic regions. Here we focus on the level of a single gene or small group of genes and investigate how the effects of background selection caused by nonsynonymous mutations are influenced by the lengths of coding sequences, the number and length of introns, intergenic distances, neighboring genes, mutation rate, and recombination rate. We generate our predictions from estimates of the distribution of the fitness effects of nonsynonymous mutations, obtained from DNA sequence diversity data in Drosophila. Results for genes in regions with typical frequencies of crossing over in Drosophila melanogaster suggest that background selection may influence the effective population sizes of different regions of the same gene, consistent with observed differences in codon usage bias along genes. It may also help to cause the observed effects of gene length and introns on codon usage. Gene conversion plays a crucial role in determining the sizes of these effects. The model overpredicts the effects of background selection with large groups of nonrecombining genes, because it ignores Hill–Robertson interference among the mutations involved.
Natural Genetic Variation in Cuticular Hydrocarbon Expression in Male and Female Drosophila melanogaster
Authors: Foley Brad , Chenoweth Stephen F , Nuzhdin Sergey V , Blows Mark W 
Published: December 2006

Abstract
Cuticular hydrocarbons (CHCs) act as contact pheromones in Drosophila melanogaster and are an important component of several ecological traits. Segregating genetic variation in the expression of CHCs at the population level in D. melanogaster is likely to be important for mate choice and climatic adaptation; however, this variation has never been characterized. Using a panel of recombinant inbred lines (RILs) derived from a natural population, we found significant between-line variation for nearly all CHCs in both sexes. We identified 25 QTL in females and 15 QTL in males that pleiotropically influence CHC expression. There was no evidence of colocalization of QTL for homologous traits across the sexes, indicating that sexual dimorphism and low intersex genetic correlations between homologous CHCs are a consequence of largely independent genetic control. This is consistent with a pattern of divergent sexual and natural selection between the sexes.
Phylogenetic Mapping of Recombination Hotspots in Human Immunodeficiency Virus via Spatially Smoothed Change-Point Processes
Authors: Minin Vladimir N , Dorman Karin S , Fang Fang , Suchard Marc A 
Published: December 2006

AbstractWe present a Bayesian framework for inferring spatial preferences of recombination from multiple putative recombinant nucleotide sequences. Phylogenetic recombination detection has been an active area of research for the last 15 years. However, only recently attempts to summarize information from several instances of recombination have been made. We propose a hierarchical model that allows for simultaneous inference of recombination breakpoint locations and spatial variation in recombination frequency. The dual multiple change-point model for phylogenetic recombination detection resides at the lowest level of our hierarchy under the umbrella of a common prior on breakpoint locations. The hierarchical prior allows for information about spatial preferences of recombination to be shared among individual data sets. To overcome the sparseness of breakpoint data, dictated by the modest number of available recombinant sequences, we a priori impose a biologically relevant correlation structure on recombination location log odds via a Gaussian Markov random field hyperprior. To examine the capabilities of our model to recover spatial variation in recombination frequency, we simulate recombination from a predefined distribution of breakpoint locations. We then proceed with the analysis of 42 human immunodeficiency virus (HIV) intersubtype gag recombinants and identify a putative recombination hotspot.
A Distinct Type of Heterochromatin Within Drosophila melanogaster Chromosome 4
Authors: Haynes Karmella A , Gracheva Elena , Elgin Sarah C R 
Published: December 2006

Abstract
Studies of transcriptional gene silencing in Drosophila melanogaster suggest that most of chromosome 4 resembles pericentric heterochromatin. However, some modifiers of position-effect variegation, including chromosome 4 dosage and loss of SU(VAR)3-9, have different effects on silencing in pericentric vs. distal arm chromosome 4 heterochromatin, distinguishing these two heterochromatin types.
Comparative Genomics and Adaptive Selection of the ATP-Binding-Cassette Gene Family in Caenorhabditis Species
Authors: Zhao Zhongying , Thomas James H , Chen Nansheng , Sheps Jonathan A , Baillie David L 
Published: December 2006

Abstract
ABC transporters constitute one of the largest gene families in all species. They are mostly involved in transport of substrates across membranes. We have previously demonstrated that the Caenorhabditis elegans ABC family shows poor one-to-one gene orthology with other distant model organisms. To address the evolution dynamics of this gene family among closely related species, we carried out a comparative analysis of the ABC family among the three nematode species C. elegans, C. briggsae, and C. remanei. In contrast to the previous observations, the majority of ABC genes in the three species were found in orthologous trios, including many tandemly duplicated ABC genes, indicating that the gene duplication took place before speciation. Species-specific expansions of ABC members are rare and mostly observed in subfamilies A and B. C. briggsae and C. remanei orthologous ABC genes tend to cluster on trees, with those of C. elegans as an outgroup, consistent with their proposed species phylogeny. Comparison of intron/exon structures of the highly conserved ABCE subfamily members also indicates a closer relationship between C. briggsae and C. remanei than between either of these species and C. elegans. A comparison between insect and mammalian species indicates lineage-specific duplications or deletions of ABC genes, while the family size remains relatively constant. Sites undergoing positive selection within subfamily D, which are implicated in very-long-chain fatty acid transport, were identified. The evolution of these sites might be driven by the changes in food source with time.