bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased metallothionein gene expression, zinc, and zinc-dependent resistance to apoptosis in circulating monocytes during HIV viremia
Authors: Raymond Andrea D , Gekonge Bethsebah , Giri Malavika S , Hancock Aidan , Papasavvas Emmanouil , Chehimi Jihed , Kossevkov Andrew V , Nicols Calen , Yousef Malik , Mounzer Karam , Shull Jane , Kostman Jay , Showe Louise , Montaner Luis J 
Published: June 2010

Abstract
Differential expression of metallothionein genes and high intracellular zinc promote monocyte survival during HIV infection.
Circulating monocytes exhibit an apoptotic resistance phenotype during HIV viremia in association with increased MT expression. MTs are known to play an important role in zinc metabolism and immune function. We now show, in a cross-sectional study using peripheral monocytes, that expression of MT1 isoforms E, G, H, and X is increased significantly in circulating monocyte cells from HIV+ subjects during chronic viremic episodes as compared with uninfected subjects. This increase in expression is also observed during acute viremia following interruption of suppressive ART. Circulating monocytes from HIV+ donors were also found to have elevated zinc importer gene Zip8 expression in conjunction with elevated intracellular zinc levels in contrast to CD4+T-lymphocytes. In vitro HIV-1 infection studies with elutriated MDM confirm a direct relation between HIV-1 infection and increased MDM MT1 (isoform G) gene expression and increased intracellular zinc levels. A direct link between elevated zinc levels and apoptosis resistance was established using a cell-permeable zinc chelator TPEN, which reversed apoptosis resistance effectively in monocytes from HIV-infected to levels comparable with uninfected controls. Taken together, increases in MT gene expression and intracellular zinc levels may contribute directly to maintenance of an immune-activated monocyte by mediating an increased resistance to apoptosis during active HIV-1 viremia.
Dendritic cells interact with CD4 T cells in intestinal mucosa
Authors: Inman Charlotte F , Singha Sakon , Lewis Marie , Bradley Ben , Stokes Chris , Bailey Mick 
Published: June 2010

Abstract
Dendritic cells interact with T cells in intestinal mucosa in an MHCII-dependent manner, suggesting presentation outside organized lymphoid tissue may be important in determining T cell phenotype.
Absence of lymph nodes in nonmammalian species, expression of MHCII by APCs in the periphery, and the recent findings that T cells can change their polarization status after presentation in the lymph nodes imply a role for MHCII-mediated presentation outside the organized lymphoid tissue. This study shows that MHCII+ ECs and DCs from the intestinal mucosa of the pig can present antigen to T cells in vitro. In vivo, APCs colocalize with T cells in pig and mouse intestinal mucosa. In the pig, endothelium is involved in these interactions in neonates but not in adults, indicating different roles for stromal and professional APCs in the neonate compared with the adult. The ratio of expression of DQ and DR MHCII locus products was lower on ECs than on other mucosal APCs, indicating that the two types of cells present different peptide sets. Adult nonendothelial APCs expressed a higher ratio of DQ/DR than in neonates. These results suggest that mucosal DCs can present antigen locally to primed T cells and that stromal APCs are recruited to these interactions in some cases. This raises the possibility that local presentation may influence T cell responses at the effector stage after initial presentation in the lymph node.
Case Article—Revenue Management at Harrah's Entertainment, Inc.
Authors: Agrawal Narendra , Cohen Morris A. , Gans Noah 
Published: June 2010

Harrah's Entertainment operates a highly diversified network of gambling facilities in the United States and the United Kingdom. This case introduces students to Harrah's use of price controls for hotel revenue management: how it works, how it integrates with Harrah's Total Rewards loyalty card, and how it might be changed. Within the context of a course on revenue management or service operations, the case can be used effectively to discuss principles of revenue management and to demonstrate the use of a number of quantitative analysis techniques to design and optimize revenue management systems. Case Teaching Note: Interested Instructors please see the Instructor Materials page for access to the restricted materials. To maintain the integrity and usefulness of cases published in ITE, unapproved distribution of the case teaching notes and other restricted materials to any other party is prohibited.
The Role of Colesevelam Hydrochloride in Hypercholesterolemia and Type 2 Diabetes Mellitus
Authors: Brunetti Luigi , Hermes-DeSantis Evelyn R 
Published: June 2010

Objective: To evaluate the safety and efficacy of colesevelam hydrochloride for the treatment of hypercholesterolemia and type 2 diabetes mellitus. Data Sources: Literature retrieval was accessed through MEDLINE/PubMed (1950–March 2010), Web of Science (1980–March 2010), and International Pharmaceutical Abstracts (1977–March 2010) using the terms colesevelam, dyslipidemia, hypercholesterolemia, and type 2 diabetes mellitus. References from publications identified were reviewed for additional resources. In addition, abstracts presented at the most recent (2009) American Diabetes Association, American Association of Clinical Endocrinologists, and European Association for the Study of Diabetes annual meetings were searched for relevant original research. Study Selection and Data Extraction: All articles in English identified from the data sources were evaluated. All relevant studies evaluating the safety and efficacy of colesevelam in hypercholesterolemia and/or type 2 diabetes mellitus were included. Priority was placed on data obtained from human randomized controlled trials. Data Synthesis: Seventeen clinical trials were reviewed and evaluated. Of the clinical trials evaluating colesevelam in hypercholesterolemia, 3 evaluated monotherapy, 4 evaluated combination therapy with hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, and 6 evaluated combination therapy with other lipid-lowering therapies. In the type 2 diabetes mellitus trials, colesevelam was evaluated in combination with metformin, sulfonylureas, insulin, and rosiglitazone and sitagliptin. A review of the clinical trials provided evidence that colesevelam monotherapy effectively reduces low-density lipoprotein cholesterol (LDL-C). Additionally, the use of colesevelam in combination with other lipid-lowering therapies further reduces LDL-C. Colesevelam also effectively reduces hemoglobin A1c in patients with type 2 diabetes mellitus. The safety and tolerability of colesevelam appear to be improved from that of older-generation bile acid sequestrants, with adverse effects similar to those with placebo in monotherapy and type 2 diabetes mellitus trials. Conclusions: Colesevelam is a safe and effective option for the treatment of hypercholesterolemia and type 2 diabetes mellitus. It can fulfill a useful role in combination with HMG-CoA reductase inhibitors for hypercholesterolemia and should be considered in patients with type 2 diabetes mellitus with concomitant hypercholesterolemia.
A Population Study of the Frequency of High-Dose Acetaminophen Prescribing and Dispensing
Authors: Albertson Timothy E , Walker Victor M , Stebbins Marilyn R , Ashton Elisa W , Owen Kelly P , Sutter Mark E 
Published: June 2010

Background: Recurrent intake of 4 g/day or more of acetaminophen has been associated with elevation of serum alanine aminotransferase (ALT) levels in 30–40% of the exposed population and may result in hepatotoxicity. Objective: To describe the frequency that patients are prescribed acetaminophen doses that exceed 4 g/day across a large population. Methods: Using California's Medicaid (MediCal) fee-for-service population, pharmacy claims including over-the-counter (OTC) medications were examined for prescriptions that could result in acetaminophen doses of 4 g/day or more. The period studied, October 2004 through September 2005, was before the Part D pharmacy benefit was available to dually eligible Medicare patients when all prescriptions were covered by the MediCal claims process. Results: During the pre-Part D evaluation period, approximately 3.27 million beneficiaries were enrolled in the fee-for-service MediCal program. A total of 192,716 (5.9%) were potentially exposed to at least 1 day of 4 g/day or more of acetaminophen. Of those, 769 patients were potentially exposed to at least 1 day of 16 g/day or more. A total of 2664 beneficiaries were dispensed prescriptions and OTC products that, if taken as directed, would have resulted in more than 100 days of acetaminophen doses of 4 g/day or more during the study year. Conclusions: Despite electronic systems designed to warn dispensing pharmacists of duplications of drug class and cumulative excessive doses, potentially toxic amounts of acetaminophen are commonly prescribed and dispensed to this population. Better systems, increased awareness, and education of patients, prescribers, and pharmacists are needed to reduce this potential toxic exposure.
Pitfalls Associated with the Use of Liquid Chromatography–Tandem Mass Spectrometry in the Clinical Laboratory
Authors: Vogeser Michael , Seger Christoph 
Published: June 2010

BACKGROUND
Novel mass spectrometric techniques such as atmospheric pressure ionization and tandem mass spectrometry have substantially extended the spectrum of clinical chemistry methods during the past decade. In particular, liquid chromatography tandem–mass spectrometry (LC-MS/MS) has become a standard tool in research laboratories as well as in many clinical laboratories. Although LC-MS/MS has features that suggest it has a very high analytical accuracy, potential sources of inaccuracy have recently been identified.

CONTENT
The sources of inaccuracy in LC-MS/MS methods used in the routine quantification of small molecules are described and discussed. Inaccuracy of LC-MS/MS methods can be related to the process of ionization through the insource transformation of conjugate metabolites or target analytes and may also be attributable to ionization matrix effects that have a differential impact on target analytes and internal-standard compounds. Inaccuracy can also be associated with the process of ion selection, which mainly occurs when compounds from the sample matrix share mass transitions with a target analyte. In individual assays, most potential sources of inaccuracy can be controlled by sufficient LC separation–based sample workup before MS analysis.

SUMMARY
LC-MS/MS methods should undergo rigorous and systematic validation before introduction into patient care.
Ten Research Questions for Family Therapy
Authors: Carr Alan 
Published: June 2010

A growing evidence‐base shows that family therapy works, but many gaps in our knowledge remain about the conditions under which family therapy is effective and how it works. In this paper, ten critical research questions about family therapy that need to be addressed are considered. In short these are:Is family therapy as effective in community settings as it is in specialist clinics?For what problems is family therapy cost‐effective?Does family therapy work for under‐researched problems and populations?Do social‐constructionist and narrative approaches to family therapy work?Can family therapy protocols be enhanced for non‐responders?Can family therapy be combined with other psychotherapies to effectively treat specific problems?Can family therapy be combined with pharmacotherapy to effectively treat specific problems?What specific factors contribute to the effectiveness of family therapy with particular problems?What common factors contribute to the effectiveness of family therapy?What therapist and client factors contribute to the effectiveness of family therapy?
Subjective health status in men and women with congenital adrenal hyperplasia: a population-based survey in Norway
Authors: Nermoen Ingrid , Husebye Eystein S , Svartberg Johan , Løvås Kristian 
Published: June 2010

BackgroundPatients with classical congenital adrenal hyperplasia (CAH) require life-long corticosteroid therapy, with uncertain health outcome. Investigations of subjective health status in unselected populations of adult patients are needed.ObjectiveTo identify all adult Norwegian patients with CAH and obtain population-based data on subjective and psychological health status, working ability and fertility.Patients, methods and designClassical CAH patients were identified through search in electronic diagnosis registries at all the university hospitals in Norway. The diagnosis was verified by scrutiny of medical records. The patients were invited to a questionnaire survey including medical history, and the Short Form-36 (SF-36) and Quality of Life Scale questionnaires. The questionnaire responses and fertility data were compared with normative data.ResultsWe identified 104 adult patients (101 alive) with classical CAH (63% female), yielding overall incidence at 1/20 000 live births (1/16 000 in females). Seventy-two (72%) responded; median age 38 years (range 18–72). All the SF-36 scales were significantly impaired, most pronounced for general health and vitality perception. Working disability was reported by 19% of the patients, compared with 10% in the general population. The female patients were often single, and the CAH women had only 21% of the expected number of children compared with the general population.ConclusionIn this population-based survey of patients with classical CAH, we found that subjective health status and working ability were impaired, and that fertility was reduced in females. There is a need for improvement of the medical treatment and the general care of this patient group.
Nested Association Mapping for Identification of Functional Markers
Authors: Guo Baohong , Sleper David A , Beavis William D 
Published: June 2010

Abstract
Identification of functional markers (FMs) provides information about the genetic architecture underlying complex traits. An approach that combines the strengths of linkage and association mapping, referred to as nested association mapping (NAM), has been proposed to identify FMs in many plant species. The ability to identify and resolve FMs for complex traits depends upon a number of factors including frequency of FM alleles, magnitudes of their genetic effects, disequilibrium among functional and nonfunctional markers, statistical analysis methods, and mating design. The statistical characteristics of power, accuracy, and precision to identify FMs with a NAM population were investigated using three simulation studies. The simulated data sets utilized publicly available genetic sequences and simulated FMs were identified using least-squares variable selection methods. Results indicate that FMs with simple additive genetic effects that contribute at least 5% to the phenotypic variability in at least five segregating families of a NAM population consisting of recombinant inbred progeny derived from 28 matings with a single reference inbred will have adequate power to accurately and precisely identify FMs. This resolution and power are possible even for genetic architectures consisting of disequilibrium among multiple functional and nonfunctional markers in the same genomic region, although the resolution of FMs will deteriorate rapidly if more than two FMs are tightly linked within the same amplicon. Finally, nested mating designs involving several reference parents will have a greater likelihood of resolving FMs than single reference designs.
Gene Duplication, Gene Conversion and the Evolution of the Y Chromosome
Authors: Connallon Tim , Clark Andrew G 
Published: June 2010

AbstractNonrecombining chromosomes, such as the Y, are expected to degenerate over time due to reduced efficacy of natural selection compared to chromosomes that recombine. However, gene duplication, coupled with gene conversion between duplicate pairs, can potentially counteract forces of evolutionary decay that accompany asexual reproduction. Using a combination of analytical and computer simulation methods, we explicitly show that, although gene conversion has little impact on the probability that duplicates become fixed within a population, conversion can be effective at maintaining the functionality of Y-linked duplicates that have already become fixed. The coupling of Y-linked gene duplication and gene conversion between paralogs can also prove costly by increasing the rate of nonhomologous crossovers between duplicate pairs. Such crossovers can generate an abnormal Y chromosome, as was recently shown to reduce male fertility in humans. The results represent a step toward explaining some of the more peculiar attributes of the human Y as well as preliminary Y-linked sequence data from other mammals and Drosophila. The results may also be applicable to the recently observed pattern of tetraploidy and gene conversion in asexual, bdelloid rotifers.
Patterns and Processes of Genome-Wide Divergence Between North American and AfricanDrosophila melanogaster
Authors: Yukilevich Roman , Turner Thomas L , Aoki Fumio , Nuzhdin Sergey V , True John R 
Published: June 2010

AbstractGenomic tools and analyses are now being widely used to understand genome-wide patterns and processes associated with speciation and adaptation. In this article, we apply a genomics approach to the model organism Drosophila melanogaster. This species originated in Africa and subsequently spread and adapted to temperate environments of Eurasia and the New World, leading some populations to evolve reproductive isolation, especially between cosmopolitan and Zimbabwean populations. We used tiling arrays to identify highly differentiated regions within and between North America (the United States and Caribbean) and Africa (Cameroon and Zimbabwe) across 63% of the D. melanogaster genome and then sequenced representative fragments to study their genetic divergence. Consistent with previous findings, our results showed that most differentiation was between populations living in Africa vs. outside of Africa (i.e., “out-of-Africa” divergence), with all other geographic differences being less substantial (e.g., between cosmopolitan and Zimbabwean races). The X chromosome was much more strongly differentiated than the autosomes between North American and African populations (i.e., greater X divergence). Overall differentiation was positively associated with recombination rates across chromosomes, with a sharp reduction in regions near centromeres. Fragments surrounding these high FST sites showed reduced haplotype diversity and increased frequency of rare and derived alleles in North American populations compared to African populations. Nevertheless, despite sharp deviation from neutrality in North American strains, a small set of bottleneck/expansion demographic models was consistent with patterns of variation at the majority of our high FST fragments. Although North American populations were more genetically variable compared to Europe, our simulation results were generally consistent with those previously based on European samples. These findings support the hypothesis that most differentiation between North America and Africa was likely driven by the sorting of African standing genetic variation into the New World via Europe. Finally, a few exceptional loci were identified, highlighting the need to use an appropriate demographic null model to identify possible cases of selective sweeps in species with complex demographic histories.
Regulation of Odor Receptor Genes in Trichoid Sensilla of the Drosophila Antenna
Authors: Miller Carson J , Carlson John R 
Published: June 2010

AbstractThis study concerns the problem of odor receptor gene choice in the fruit fly Drosophila melanogaster. From a family of 60 Odor receptor genes, only one or a small number are selected for expression by each olfactory receptor neuron. Little is known about how an olfactory receptor neuron selects a receptor, or how the nucleotide sequences flanking a receptor gene dictate its expression in a particular neuron. Previous investigation has primarily concerned the maxillary palp, the simpler of the fly's two olfactory organs. Here we focus on genes encoding four antennal receptors that respond to fly odors in an in vivo expression system. To investigate the logic of odor receptor expression, we carry out a genetic analysis of their upstream regulatory sequences. Deletion analysis reveals that relatively short regulatory regions are sufficient to confer expression in the appropriate neurons, with limited if any misexpression. We find evidence for both positive and negative regulation. Multiple repressive functions restrict expression to the antenna, to a region of the antenna, and to neurons. Through deletion and base substitution mutagenesis we identify GCAATTA elements and find evidence that they act in both positive and negative regulation.
YNot a Dead End: Epistatic Interactions BetweenY-Linked Regulatory Polymorphisms and Genetic Background Affect Global Gene Expression inDrosophila melanogaster
Authors: Jiang Pan-Pan , Hartl Daniel L , Lemos Bernardo 
Published: June 2010

AbstractThe Y chromosome, inherited without meiotic recombination from father to son, carries relatively few genes in most species. This is consistent with predictions from evolutionary theory that nonrecombining chromosomes lack variation and degenerate rapidly. However, recent work has suggested a dynamic role for the Y chromosome in gene regulation, a finding with important implications for spermatogenesis and male fitness. We studied Y chromosomes from two populations of Drosophila melanogaster that had previously been shown to have major effects on the thermal tolerance of spermatogenesis. We show that these Y chromosomes differentially modify the expression of hundreds of autosomal and X-linked genes. Genes showing Y-linked regulatory variation (YRV) also show an association with immune response and pheromone detection. Indeed, genes located proximal to the euchromatin–heterochromatin boundary of the X chromosome appear particularly responsive to Y-linked variation, including a substantial number of odorant-binding genes. Furthermore, the data show significant regulatory interactions between the Y chromosome and the genetic background of autosomes and X chromosome. Altogether, our findings support the view that interpopulation, Y-linked regulatory polymorphisms can differentially modulate the expression of many genes important to male fitness, and they also point to complex interactions between the Y chromosome and genetic background affecting global gene expression.
QIP, a Protein That Converts Duplex siRNA Into Single Strands, Is Required for Meiotic Silencing by Unpaired DNA
Authors: Xiao Hua , Alexander William G , Hammond Thomas M , Boone Erin C , Perdue Tony D , Pukkila Patricia J , Shiu Patrick K T 
Published: June 2010

AbstractRNA interference (RNAi) depends on the production of small RNA to regulate gene expression in eukaryotes. Two RNAi systems exist to control repetitive selfish elements in Neurospora crassa. Quelling targets transgenes during vegetative growth, whereas meiotic silencing by unpaired DNA (MSUD) silences unpaired genes during meiosis. The two mechanisms require common RNAi proteins, such as RNA-directed RNA polymerases, Dicers, and Argonaute slicers. We have previously demonstrated that, while Quelling depends on the redundant dicer activity of DCL-1 and DCL-2, only DCL-1 is required for MSUD. Here, we show that QDE-2-interacting protein (QIP), an exonuclease that is important for the production of single-stranded siRNA during Quelling, is also required for MSUD. QIP is crucial for sexual development and is shown to colocalize with other MSUD proteins in the perinuclear region.