bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vitro Fertilization Improves Childhood Growth and Metabolism
Authors: Miles Harriet L. , Hofman Paul L. , Peek John , Harris Mark , Wilson Dyanne , Robinson Elizabeth M. , Gluckman Peter D. , Cutfield Wayne S.
Published: June 2007

Background: There is limited information regarding the long-term outcome of children born after in vitro fertilization (IVF), although an increase in rare imprinted gene disorders such as Beckwith-Wiedemann syndrome has been reported.

Methods: We recruited healthy, prepubertal children born at term after singleton pregnancy. The children in the study group were conceived using IVF with fresh embryo transfer, whereas controls were naturally conceived. Anthropometric measurements, bone age, dual-energy x-ray absorptiometry, fasting serum glucose, insulin, lipid profile, IGF-I and -II, and IGF-binding proteins 1, 2, and 3 were performed.

Results: There were 69 IVF children aged 5.9 ± 0.2 yr and 71 control children aged 6.9 yr. IVF children were taller than controls when corrected for parents’ heights (height sd score of 1.05 ± 0.1 vs. 0.51 ± 0.11, P = 0.001) with higher levels of serum IGF-II (850 ± 24 vs. 773 ± 24 μg/liter, P = 0.03), higher IGF-I to IGF-binding protein 3 ratio (P = 0.04), and a trend toward higher IGF-I (105 ± 4 vs. 92 ± 4 μg/liter, P = 0.06). IVF children had higher high-density lipoprotein (1.67 ± 0.04 mmol/liter vs. 1.53 ± 0.04 mmol/liter, P = 0.02), lower triglycerides (0.65 ± 0.04 mmol/liter vs. 0.78 ± 0.04 mmol/liter, P = 0.02), and a lower total to high-density lipoprotein cholesterol ratio (2.58 vs. 2.86, P = 0.01). There were no differences in body composition.

Conclusions: IVF children are taller with higher IGF-I and IGF-II levels and have a slightly more favorable lipid profile. We speculate that IVF results in epigenetic change through altered methylation of genes involved in growth and metabolism. IVF programs should consider long-term longitudinal follow-up of IVF offspring.
Association of Prostaglandin E Synthase 2 (PTGES2) Arg298His Polymorphism with Type 2 Diabetes in Two German Study Populations
Authors: Nitz Inke , Fisher Eva , Grallert Harald , Li Yun , Gieger Christian , Rubin Diana , Boeing Heiner , Spranger Joachim , Lindner Inka , Schreiber Stefan , Rathmann Wolfgang , Gohlke Henning , Döring Angela , Wichmann H.-Erich , Schrezenmeir Jürgen , Döring Frank , Illig Thomas
Published: June 2007

Context: On the basis of its chromosomal localization and its role in the synthesis of the antilipolytic compound prostaglandin E2, the prostaglandin E synthase 2 (PTGES2) is a candidate gene for type 2 diabetes.

Objective: The aim of the present study was to investigate whether genetic variants in the PTGES2 gene are associated with type 2 diabetes.

Results: Sequencing of the PTGES2 gene revealed one nonsynonymous coding single-nucleotide polymorphism (SNP) (Arg298His, rs13283456) and a previously unknown promoter SNP g.-417G>T. Both SNPs and additional haplotype tagging SNPs (rs884115, rs10987883, rs4837240) were genotyped in a nested case-control study of 192 incident type 2 diabetes subjects and 384 controls (European Prospective Investigation into Cancer and Nutrition-Potsdam). Carriers of the minor allele of Arg298His had a lower risk to develop the disease [odds ratio (OR) 0.63, 95% confidence interval (CI) 0.41–0.97, P = 0.04], compared with homozygous individuals with the common allele. The PTGES2 Arg298His polymorphism was reinvestigated in a population-based cross-sectional study (Cooperative Health Research in the Augsburg Region) consisting of 239 individuals with impaired glucose tolerance, 226 with type 2 diabetes, and 863 normoglycemic controls. In this study population, the Arg298His polymorphism was significantly associated with impaired glucose tolerance (OR 0.68, 95% CI 0.50–0.93, P = 0.007) and type 2 diabetes (OR 0.61, 95% CI 0.43–0.86, P = 0.004). A pooled analysis of data from both study populations revealed reduced risk of type 2 diabetes (OR 0.62, 95% CI 0.47–0.81, P = 0.0005) in PTGES2 298His allele carriers.

Conclusion: We obtained evidence from two Caucasian study populations that the His298-allele of PTGES2 Arg298His confers to reduced risk of type 2 diabetes.
SH2B1 Enhances Leptin Signaling by Both Janus Kinase 2 Tyr813 Phosphorylation-Dependent and -Independent Mechanisms
Authors: Li Zhiqin , Zhou Yingjiang , Carter-Su Christin , Myers Martin G. , Rui Liangyou
Published: June 2007

Leptin controls body weight by activating its long form receptor (LEPRb). LEPRb binds to Janus kinase 2 (JAK2), a cytoplasmic tyrosine kinase that mediates leptin signaling. We previously reported that genetic deletion of SH2B1 (previously known as SH2-B), a JAK2-binding protein, results in severe leptin-resistant and obese phenotypes, indicating that SH2B1 is a key endogenous positive regulator of leptin sensitivity. Here we show that SH2B1 regulates leptin signaling by multiple mechanisms. In the absence of leptin, SH2B1 constitutively bound, via its non-SH2 domain region(s), to non-tyrosyl-phosphorylated JAK2, and inhibited JAK2. Leptin stimulated JAK2 phosphorylation on Tyr813, which subsequently bound to the SH2 domain of SH2B1. Binding of the SH2 domain of SH2B1 to phospho-Tyr813 in JAK2 enhanced leptin induction of JAK2 activity. JAK2 was required for leptin-stimulated phosphorylation of insulin receptor substrate 1 (IRS1), an upstream activator of the phosphatidylinositol 3-kinase pathway. Overexpression of SH2B1 enhanced both JAK2- and JAK2(Y813F)-mediated tyrosine phosphorylation of IRS1 in response to leptin, even though SH2B1 did not enhance JAK2(Y813F) activation. Leptin promoted the interaction of SH2B1 with IRS1. These data suggest that constitutive SH2B1-JAK2 interaction, mediated by the non-SH2 domain region(s) of SH2B1 and the non-Tyr813 region(s) in JAK2, increases the local concentration of SH2B1 close to JAK2 and inhibits JAK2 activity. Leptin-stimulated SH2B1-JAK2 interaction, mediated by the SH2 domain of SH2B1 and phospho-Tyr813 in JAK2, promotes JAK2 activation, thus globally enhancing leptin signaling. SH2B1-IRS1 interaction facilitates IRS1 phosphorylation by recruiting IRS1 to JAK2 and/or by protecting IRS1 from dephosphorylation, thus specifically enhancing leptin stimulation of the phosphatidylinositol 3-kinase pathway.
p27kip1 (Cyclin-Dependent Kinase Inhibitor 1B) Controls Ovarian Development by Suppressing Follicle Endowment and Activation and Promoting Follicle Atresia in Mice
Authors: Rajareddy Singareddy , Reddy Pradeep , Du Chun , Liu Lian , Jagarlamudi Krishna , Tang Wenli , Shen Yan , Berthet Cyril , Peng Stanford L. , Kaldis Philipp , Liu Kui
Published: June 2007

In humans, the molecular mechanisms underlying ovarian follicle endowment and activation, which are closely related to the control of female reproduction, occurrence of menopause, and related diseases such as premature ovarian failure, are poorly understood. In the current study, we provide several lines of genetic evidence that the cyclin-dependent kinase (Cdk) inhibitor 1B (commonly known as p27kip1 or p27) controls ovarian development in mice by suppressing follicle endowment and activation, and by promoting follicle death. In p27-deficient (p27−/−) mice, postnatal follicle assembly was accelerated, and the number of endowed follicles was doubled as compared with p27+/+ mice. Moreover, in p27−/− ovaries the primordial follicle pool was prematurely activated once it was endowed, and at the same time the massive follicular death that occurs before sexual maturity was rescued by loss of p27. In early adulthood, however, the overactivated follicular pool in p27−/− ovaries was largely depleted, causing premature ovarian failure. Furthermore, we have extensively studied the molecular mechanisms underlying the above-mentioned phenotypes seen in p27−/− ovaries and have found that p27 controls follicular development by several distinct mechanisms at different stages of development of the ovary. For example, p27 controls oocyte growth by suppressing the functions of Cdk2/Cdc2-cyclin A/E1 in oocytes that are arrested at the diplotene stage of meiosis I. This function of p27 is distinct from its well-known role as a suppressor of cell cycle progression. In addition, we have found that p27 activates the caspase-9-caspase-3-caspase-7-poly (ADP-ribose) polymeraseapoptotic cascade by inhibiting Cdk2/Cdc2-cyclin A/B1 kinase activities in follicles, thereby inducing follicle atresia. Our results suggest that the p27 gene is important in determining mammalian ovarian development. This study therefore provides insight into ovary-borne genetic aberrations that cause defects in folliculogenesis and infertility in humans.
Defective osteoblast function in ICAP-1-deficient mice
Authors: Bouvard Daniel , Aszodi Attila , Kostka Günter , Block Marc R. , Albigès-Rizo Corinne , Fässler Reinhard
Published: June 2007

The integrin receptor family plays important roles in cell-to-cell and cell-to-extracellular matrix interactions through the recruitment of accessory molecules. One of them, the integrin cytoplasmic domain-associated protein-1(ICAP-1; also known as ITGB1BP1), specifically interacts with the cytoplasmic domain of the β1 integrin subunit and negatively regulates its function in vitro. To address the role of ICAP-1 in vivo, we ablated the Icap-1 gene in mice. We report an unexpected role of ICAP-1 in osteoblast function during bone development. Icap-1-deficient mice suffer from reduced osteoblast proliferation and delayed bone mineralization,resulting in the retarded formation of bone sutures. In vitro studies reveal that primary and immortalized Icap-1-null osteoblasts display enhanced adhesion and spreading on extracellular matrix substrates, probably owing to an increase in β1 integrin activation. Finally, we provide evidence that ICAP-1 promotes differentiation of osteoprogenitors by supporting their condensation through modulating the integrin high affinity state.
Regulation of tendon differentiation by scleraxis distinguishes force-transmitting tendons from muscle-anchoring tendons
Authors: Murchison Nicholas D. , Price Brian A. , Conner David A. , Keene Douglas R. , Olson Eric N. , Tabin Clifford J. , Schweitzer Ronen
Published: June 2007

The scleraxis (Scx) gene, encoding a bHLH transcription factor, is expressed in the progenitors and cells of all tendon tissues. To determine Scx function, we produced a mutant null allele. Scx-/- mice were viable, but showed severe tendon defects, which manifested in a drastically limited use of all paws and back muscles and a complete inability to move the tail. Interestingly, although the differentiation of all force-transmitting and intermuscular tendons was disrupted, other categories of tendons, the function of which is mainly to anchor muscles to the skeleton,were less affected and remained functional, enabling the viability of Scx-/- mutants. The force-transmitting tendons of the limbs and tail varied in the severity to which they were affected, ranging from dramatic failure of progenitor differentiation resulting in the loss of segments or complete tendons, to the formation of small and poorly organized tendons. Tendon progenitors appeared normal in Scx-/-embryos and a phenotype resulting from a failure in the condensation of tendon progenitors to give rise to distinct tendons was first detected at embryonic day (E)13.5. In the tendons that persisted in Scx-/-mutants, we found a reduced and less organized tendon matrix and disorganization at the cellular level that led to intermixing of tenocytes and endotenon cells. The phenotype of Scx-/- mutants emphasizes the diversity of tendon tissues and represents the first molecular insight into the important process of tendon differentiation.
Cohesin-dependent regulation of Runx genes
Authors: Horsfield Julia A. , Anagnostou Sasha H. , Hu Jimmy Kuang-Hsien , Cho Kitty Hsiao Yu , Geisler Robert , Lieschke Graham , Crosier Kathryn E. , Crosier Philip S.
Published: June 2007

Runx transcription factors determine cell fate in many lineages. Maintaining balanced levels of Runx proteins is crucial, as deregulated expression leads to cancers and developmental disorders. We conducted a forward genetic screen in zebrafish for positive regulators of runx1that yielded the cohesin subunit rad21. Zebrafish embryos lacking Rad21, or cohesin subunit Smc3, fail to express runx3 and lose hematopoietic runx1 expression in early embryonic development. Failure to develop differentiated blood cells in rad21 mutants is partially rescued by microinjection of runx1 mRNA. Significantly,monoallelic loss of rad21 caused a reduction in the transcription of runx1 and of the proneural genes ascl1a and ascl1b,indicating that downstream genes are sensitive to Rad21 dose. Changes in gene expression were observed in a reduced cohesin background in which cell division was able to proceed, indicating that cohesin might have a function in transcription that is separable from its mitotic role. Cohesin is a protein complex essential for sister chromatid cohesion and DNA repair that also appears to be essential for normal development through as yet unknown mechanisms. Our findings provide evidence for a novel role for cohesin in development, and indicate potential for monoallelic loss of cohesin subunits to alter gene expression.
G-protein-coupled signals control cortical actin assembly by controlling cadherin expression in the earlyXenopusembryo
Authors: Tao Qinghua , Nandadasa Sumeda , McCrea Pierre D. , Heasman Janet , Wylie Christopher
Published: June 2007

During embryonic development, each cell of a multicellular organ rudiment polymerizes its cytoskeletal elements in an amount and pattern that gives the whole cellular population its characteristic shape and mechanical properties. How does each cell know how to do this? We have used the Xenopusblastula as a model system to study this problem. Previous work has shown that the cortical actin network is required to maintain shape and rigidity of the whole embryo, and its assembly is coordinated throughout the embryo by signaling through G-protein-coupled receptors. In this paper, we show that the cortical actin network colocalizes with foci of cadherin expressed on the cell surface. We then show that cell-surface cadherin expression is both necessary and sufficient for cortical actin assembly and requires the associated catenin p120 for this function. Finally, we show that the previously identified G-protein-coupled receptors control cortical actin assembly by controlling the amount of cadherin expressed on the cell surface. This identifies a novel mechanism for control of cortical actin assembly during development that might be shared by many multicellular arrays.
Ca2+ signaling through ryanodine receptor 1 enhances maturation and activation of human dendritic cells
Authors: Bracci Laura , Vukcevic Mirko , Spagnoli Giulio , Ducreux Sylvie , Zorzato Francesco , Treves Susan
Published: June 2007

Increases in intracellular Ca2+ concentration accompany many physiological events, including maturation of dendritic cells, professional antigen-presenting cells characterized by their ability to migrate to secondary lymphoid organs where they initiate primary immune responses. The mechanism and molecules involved in the early steps of Ca2+ release in dendritic cells have not yet been defined. Here we show that the concomitant activation of ryanodine receptor-induced Ca2+ release together with the activation of Toll-like receptors by suboptimal concentrations of microbial stimuli provide synergistic signals, resulting in dendritic cell maturation and stimulation of T cell functions. Furthermore, our results show that the initial intracellular signaling cascade activated by ryanodine receptors is different from that induced by activation of Toll-like receptors. We propose that under physiological conditions, especially when low suboptimal amounts of Toll-like receptor ligands are present, ryanodine receptor-mediated events cooperate in bringing about dendritic cell maturation.
1-Lithio-1,3-dienes: Useful Building Blocks for Cyclic Compounds
Authors: Xi Zhenfeng
Published: June 2007

In this account, our recent results on the application of substituted 1-lithio-1,3-dienes as building blocks for the preparation of a wide variety of cyclic compounds and linear compounds are briefly summarized. Results have revealed that the essential factor which makes 1-lithio-1,3-diene derivatives useful and unique as building blocks is the intra-cooperation between the alkenyllithium moiety and the butadienyl skeleton, notwithstanding that the alkenyllithium moiety itself reacts with organic substrates in the usual way. In addition, the substitution patterns and the nature of the substituents on the butadienyl skeleton have been demonstrated to affect remarkably the reaction pathways of 1-lithio-1,3-diene derivatives.
Ultrafast Dynamics in Biological Systems and in Nano-Confined Environments
Authors: Sahu Kalyanasis , Mondal Sudip Kumar , Ghosh Subhadip , Bhattacharyya Kankan
Published: June 2007

Ultrafast chemical dynamics in a nano-confined system is very different from that in a bulk liquid. In this account, we give an overview on recent femtosecond study on dynamics of ultrafast chemical processes in the nanocavity of a biological system. Dynamics in a biological system crucially depends on the location of the fluorescent probe. We show that one can study solvation dynamics in different regions (i.e. spatially resolve) by variation of the excitation wavelength. We discuss two interesting cases of how structure affects dynamics. First, solvation dynamics of two protein folding intermediates of cytochrome c is found to be differ significantly in the ultrafast initial part (< 20 ps). Second, methyl substitution of the OH group in a cyclodextrin is shown to slow down the initial part of solvation dynamics quite dramatically. The most interesting observation is the discovery of the ultraslow component of solvation dynamics which is 100–1000 times slower compared to bulk water. The electron- and proton-transfer processes in a nano-confined system are found to be markedly retarded because of slow solvation and structural constraints. Close proximity of the reactants in a confined system is expected to accelerate dynamics of bi-molecular processes. This is illustrated by ultrafast fluorescence resonance energy transfer (FRET) in ≈1 ps time scale between a donor and an acceptor in a micelle. Finally, it is demonstrated that the decay of fluorescence anisotropy provides structural information (e.g. size of a cyclodextrin inclusion complex) and may be used to detect formation of a nano-aggregate.
Development of 2,2′-Iminodiethanol Selective Production Process Using Shape-Selective Pentasil-Type Zeolite Catalyst
Authors: Tsuneki Hideaki , Kirishiki Masaru , Oku Tomoharu
Published: June 2007

Ethanolamines are produced on an industrial scale exclusively by the reaction of ethylene oxide with an aqueous solution of ammonia. The reaction is a typical consecutive reaction with three steps; therefore, it is difficult to produce 2,2′-iminodiethanol (the second product of the reaction) with high selectivity by conventional means. We developed a catalytic 2,2′-iminodiethanol selective production process using a pentasil-type zeolite catalyst modified with rare earth elements. This highly active catalyst was able to recognize the difference at molecular level between 2,2′-iminodiethanol and 2,2′,2″-nitrilotriethanol; 2,2′,2″-nitrilotriethanol was not formed in its micropore. We also succeeded in producing a binderless molded zeolite catalyst that does not form problematic impurities and that has a shape suitable for a fixed-bed reactor. The problem of activity deterioration was overcome by developing a regeneration process using high-temperature and high-density ammonia gas as a rinse medium.
Thermal Analyses of Phospholipid Mixtures by Differential Scanning Calorimetry and Effect of Doping with a Bolaform Amphiphile
Authors: Sasaki Ryo , Sasaki Hirotaka , Fukuzawa Seketsu , Kikuchi Jun , Hirota Hiroshi , Tachibana Kazuo
Published: June 2007

Morphological phases of DMPC/DHPC mixtures have already been investigated by using SANS, SAXS, NMR, and fluorescence-based techniques, as well as cryo-TEM, in which the manner of temperature is changed stepwise. We continuously monitored temperature-dependent phase transitions of DMPC/DHPC mixtures by DSC. We observed four significant transitions, two of which (transitions 1 and 4) were newly discovered in our current study. It was shown that bicelles have phase transitions similar to vesicles, and we proposed a phase diagram of DMPC/DHPC mixtures based on a continuous temperature change method. Such a phase diagram, in which transition temperatures are shown clearly, has never been reported to our knowledge. Moreover, we studied the doping effect of a synthetic bolaform amphiphile, which is used to construct stable model membranes, and found that the temperature range of the magnetically aligned state shifted to a higher temperature. This result indicates that doping synthetic phospholipids, which is done to create a thermostable membrane, is useful for stabilizing bicelles, worm-like micelles, or perforated lamellae. Such applications might be relevant to a variety of experiments, including those that utilize DMPC/DHPC mixtures as model membranes or alignment media.
Synthesis and Catalysis of Polymer-Protected Pd/Ag/Rh Trimetallic Nanoparticles with a Core–Shell Structure
Authors: Matsushita Toru , Shiraishi Yukihide , Horiuchi Shin , Toshima Naoki
Published: June 2007

Colloidal dispersions of polymer-protected Pd/Ag/Rh trimetallic nanoparticles were synthesized via self-organization by mixing colloidal dispersions of polymer-protected Rh nanoparticles with those of polymer-protected Pd/Ag bimetallic nanoparticles with a core–shell (Pd-core/Ag-shell) structure, which were prepared in advance by a sacrificial hydrogen-reduction method. The Pd/Ag/Rh trimetallic nanoparticles appeared to have a triple core–shell (Pd-core/Ag-interlayer/Rh-shell) structure on the basis of UV–vis absorption spectra, FT-IR spectra of adsorbed CO, TEM, HR-TEM, and EF-TEM observation. The spontaneously formed trimetallic nanoparticles having an atomic composition of Pd/Ag/Rh = 1/2/13.5 and an average diameter of 2.2 nm showed the highest catalytic activity among the metal nanoparticle catalysts tested here for hydrogenation of methyl acrylate at 30 °C under atmosphere of hydrogen.
Self-Medication Practices with Antibiotics and Antimalarials Among Sudanese Undergraduate University Students
Authors: Awad Abdelmoneim I , Eltayeb Idris B
Published: June 2007

Background:

In many developing countries, up to 60–80% of health problems are self-medicated.

Objective:

To estimate the prevalence of self-medication with antibiotics and/or antimalarials and identify factors promoting such use among university students in Sudan.

Methods:

A descriptive cross-sectional study was performed, using a pretested questionnaire on a sample of 1300 students selected from 5 universities in Khartoum State, Sudan.

Results:

Eight hundred ninety-one (79.5%; 95% CI 77.0 to 81.8) students from the study population had used antibiotics or antimalarials without a prescription within 1–2 months prior to the study. Four hundred ninety (55%; 95% CI 51.7 to 58.3) of the respondents stated that they had used antibiotics, 39 (4.4%; 95% CI 3.2 to 6.0) had used antimalarials, and 362 (40.6%; 95% CI 37.4 to 43.9) had used both. Overall, self-medication with antibiotics or antimalarials was significantly more common among students 21 years of age or older compared with those 20 years of age or younger (OR 1.55; 95% CI 1.15 to 2.09; p = 0.004) and among students attending private universities compared with those attending public universities (OR 1.42; 95% CI 1.04 to 1.95; p = 0.028). Self-medication with antibiotics followed a simitar pattern, which was significantly more common among students 21 years of age or older (OR 1.36; 95% CI 1.03 to 1.81; p = 0.03) and private university respondents (OR 1.52; 95% CI 1.15 to 2.02; p = 0.003). Self-medication with antimalarials was found to be significantly less common among females (OR 0.76; 95% CI 0.59 to 0.97; p = 0.028) and higher among the 21 years or older age group (OR 1.84; 95% CI 1.42 to 2.40; p < 0.001), The most common reason indicated for self-medication was the respondents’ previous experiences with similar ailments. The main source of drugs was community pharmacies.

Conclusions:

The prevalence of self-medication with antibiotics/antimalarials among undergraduate university students in Khartoum State is high. Our findings highlight the need for planning interventions to promote the judicious use of antibiotics/antimicrobials.
Gabapentin-Induced Severe Myopathy
Authors: Tuccori Marco , Lombardo Giuseppe , Lapi Francesco , Vannacci Alfredo , Blandizzi Corrado , Tacca Mario Del
Published: June 2007

Objective:

To report and discuss a case of rhabdomyolysis in an elderly patient with neuropathic pain who was treated with gabapentin.

Case Summary:

An 85-year-old diabetic woman was hospitalized for severe pain in her lower limbs and difficulty in walking, compromising her daily activities. On admission, the woman's laboratory parameters, including creatine kinase (CK) and myoglobin, were in the normal range. Neurologic evaluation suggested a diagnosis of diabetic neuropathic pain, and therapy with gabapentin 150 mg 3 times daily was started. On the same day, the patient developed psychomotor agitation and gastric pain, which were treated with haloperidol 10 mg and lansoprazole 30 mg, respectively. In the following hours, the severity of muscular pain increased and the patient developed myopathy with acute renal failure (CK 459 U/L, myoglobin 11 437 ng/mL, creatinine 4.59 mg/dL), which worsened progressively during the next 2 days (CK 3095 U/L, myoglobin 17 000 mg/dL, creatinine 4.77 mg/dL) despite discontinuation of haloperidol and lansoprazole. No signs of trauma or edema, suggesting possible compartmental or crush syndrome, were detected. Gabapentin was then withdrawn and the patient's condition rapidly improved. Complete recovery followed in about 10 days.

Discussion:

Severe myopathy is an unexpected adverse reaction to gabapentin therapy. In this patient, a possible contribution of haloperidol or lansoprazole to the adverse event cannot be excluded. However, worsening of the clinical picture despite discontinuation of these drugs, together with rapid improvement observed after withdrawal of gabapentin, strongly suggest a causative role of gabapentin. According to the Naranjo probability scale, gabapentin was the probable cause of myopathy in this patient. The mechanism by which gabapentin may induce myopathy is unknown. The early onset of the syndrome after initiation of treatment with gabapentin in therapeutic doses is compatible with the picture of an idiosyncratic adverse response.

Conclusions:

Pathogenetic and clinical investigations are required to explore what mechanisms account for gabapentin-related muscular alterations at the time of onset, including electromyographic recordings as well as muscle and nerve histopathologic examinations. Until more information is available, clinicians should consider the possibility of discontinuing gabapentin treatment in patients showing muscular pain and signs of myopathy.
Empirically Assessing Participant Perceptions of the Research Experience in a Randomized Clinical Trial: The Women's Self-Defense Project as a Case Example
Authors: Weitlauf Julie C. , Ruzek Josef I. , Westrup Darrah A. , Lee Tina , Keller Jennifer
Published: June 2007

A growing body of empirical literature has systematically documented the reactions to research participation among participants in trauma-focused research. To date, the available data has generally presented an optimistic picture regarding participants' ability to tolerate and even find benefit from their participation. However, this literature has been largely limited to cross-sectional designs. No extant literature has yet examined the perceptions of participants with psychiatric illness who are participating in randomized clinical trials (RCTs) designed to evaluate the efficacy or effectiveness of novel trauma treatments. The authors posit that negative experiences of, or poor reactions to, the research experience in the context of a trauma-focused RCT may elevate the risk of participation. Indeed, negative reactions may threaten to undermine the potential therapeutic gains of participants and promoting early drop out from the trial. Empirically assessing reactions to research participation at the pilot-study phase of a clinical trial can both provide investigators and IRB members alike with empirical evidence of some likely risks of participation. In turn, this information can be used to help shape the design and recruitment methodology of the full-scale trial. Using data from the pilot study of the Women's Self-Defense Project as a case illustration, we provide readers with concrete suggestions for empirically assessing participants' perceptions of risk involved in their participation in behaviorally oriented clinical trials.
Research Ethics Review and Aboriginal Community Values: Can the Two Be Reconciled?
Authors: Glass Kathleen Cranley , Kaufert Joseph
Published: June 2007

Contemporary research ethics review committees (RECs) are heavily influenced by the established academic or health care institutional frameworks in which they operate, sharing a cultural, methodological and ethical perspective on the conduct of research involving humans. The principle of autonomous choice carries great weight in what is a highly individualistic decision-making process in medical practice and research. This assumes that the best protection lies in the ability of patients or research participants to make competent, voluntary, informed choices, evaluating the risks and benefits from a personal perspective. Over the past two decades, North American and international indigenous researchers, policy makers and communities have identified key issues of relevance to them, but ignored by most institutional or university-based RECs. They critique the current research review structure, and propose changes on a variety of levels in an attempt to develop more community sensitive research ethics review processes. In doing so, they have emphasized recognition of collective rights including community consent. Critics see alternative policy guidelines and community-based review bodies as challenging the current system of ethics review. Some view them as reflecting a fundamental difference in values.

In this paper, we explore these developments in the context of the political, legal and ethical frameworks that have informed REC review. We examine the process and content of these frameworks and ask how this contrasts with emerging Aboriginal proposals for community-based research ethics review. We follow this with recommendations on how current REC review models might accommodate the requirements of both communities and RECs.
Applying Research Ethics Guidelines: The View from a Sub-Saharan Research Ethics Committee
Authors: Henderson Gail E. , Corneli Amy L. , Mahoney David B. , Nelson Daniel K. , Mwansambo Charles
Published: June 2007

Considerable variation has been demonstrated in applying regulations across research ethics committees (RECs) in the U.S., U.K., and European nations. With the rise of international research collaborations, RECs in developing countries apply a variety of international regulations. We conducted a qualitative descriptive pilot study with members of the national REC in Malawi to determine criteria they use to review research, and their views on international collaborations. Qualitative content analysis demonstrated that international guidelines are interpreted in light of local African conditions such that emphasis is placed on examining benefit to the community and ensuring the informed consent process translates concepts in locally-meaningful ways. Members suggest that RECs often must comply with regulations that do not fit local conditions. Recommendations are provided for improving such international collaborations.
Reported Goals for Knowledge to Be Learned in Responsible Conduct of Research Courses
Authors: Plemmons Dena K. , Kalichman Michael W.
Published: June 2007

Education in responsible conduct of research (RCR) has been a required part of training for students on U. S. National Institutes of Health (NIH) training grants for over 15 years. However, there is little evidence of commonly accepted goals for RCR instruction, making it difficult to assess effectiveness. As part of a larger study examining RCR instructors' goals for RCR education, this report focuses on those reported goals categorized as knowledge. To identify RCR instructors, e-mail requests were sent to the 116 recipients of NIH training grants awarded in 2000. Of 67 verified RCR instructors, 50 (75% response rate) from 37 different institutions were successfully interviewed. Despite a shared sense of the basics to be taught in RCR courses, these instructors were diverse in their views and understanding of goals for RCR education. This diversity suggests a challenge to be overcome not only for improving the effectiveness of RCR education, but also for attempts to assess that effectiveness.
An Investigation on the Perception of Musical Style
Authors: Storino Mariateresa , Dalmonte Rossana , Baroni Mario
Published: June 2007

THIS STUDY FOCUSES ON THE PROCESSING of Italian Baroque composer Giovanni Legrenzi's musical style. In a previous work, Baroni, Dalmonte, and Jacoboni (2003) elaborated a generative grammar and implemented it in a computer program called LEGRE that supposedly produces pieces in the style of Legrenzi. The main purpose of the present research is to assess whether a grammar can capture stylistic features that are relevant for stylistic categorization. Four experiments were designed to inquire into the cognitive processes involved in musical style categorization. The overall set of data was then used to evaluate whether a generative grammar could describe all of the features of a style, and to shed new light onto the cognitive processes involved in musical style perception.
Visual Perception of Expressiveness in Musicians' Body Movements
Authors: Dahl Sofia , Friberg Anders
Published: June 2007

MUSICIANS OFTEN MAKE GESTURES and move their bodies expressing a musical intention. In order to explore to what extent emotional intentions can be conveyed through musicians' movements, participants watched and rated silent video clips of musicians performing the emotional intentions Happy, Sad, Angry, and Fearful. In the first experiment participants rated emotional expression and movement character of marimba performances. The results showed that the intentions Happiness, Sadness, and Anger were well communicated, whereas Fear was not. Showing selected parts of the player only slightly influenced the identification of the intended emotion. In the second experiment participants rated the same emotional intentions and movement character for performances on bassoon and soprano saxophone. The ratings from the second experiment confirmed that Fear was not communicated whereas Happiness, Sadness, and Anger were recognized. The rated movement cues were similar in the two experiments and were analogous to their audio counterpart in music performance.
Physiological and Musico-Acoustic Correlates of the Chill Response
Authors: Guhn Martin , Hamm Alfons , Zentner Marcel
Published: June 2007

LISTENING TO MUSIC OFTEN EVOKES affective states that are accompanied by distinctive subjective experiences and specific physiological changes. In this study, we examined the phenomenon of chills and its concomitant physiological reactions. In a preliminary study, experimenter-selected music excerpts were played to 27 participants, and musical passages especially apt toelicit chill experiences were identified on the basis of subjective ratings. In a subsequent study with 27 new participants, subjective chill experiences and physiological responses were recorded in real time. The highest numbers of chills were experienced during musical passages characterized by similar dynamic, harmonic, and structural characteristics, which coincided with distinct patterns of heart rate and skin conductance increases. For participants experiencing a chill during these passages, increases in skin conductance were significantly larger than for participants without chills. The heart rate response did not differ between groups.
Individualism and Collectivism in America: The Case of Gun Ownership and Attitudes toward Gun Control
Authors: Celinska Katarzyna
Published: June 2007

A number of sociologists and cultural psychologists claim that the United States is a predominantly individualistic country. This article uses a unidimensional index of individualism and collectivism to analyze one of the most debated sociopolitical issues in America: gun ownership and gun control. It tests the hypothesis that the widespread gun ownership in the United States and prevailing attitudes toward gun control represent competing individualistic and collectivistic cultural traditions, respectively. The findings indicate that the index is one of the predictors of gun ownership and of attitudes about gun permits.
The Undertheorized Environment: Sociological Theory and the Ontology of Behavioral Genetics
Authors: Perrin Andrew J. , Lee Hedwig
Published: June 2007

Growing interest in the genetic contribution to human behaviors has led to the growth of the field of behavioral genetics. The authors consider the concept of “environment” in behavioral genetics and argue that sociology is in a unique position to evaluate and specify a theoretically robust concept of environment. Building on insights from classical and contemporary social theory, the authors argue that the study of genetic influence on behavior needs to incorporate sociological understandings of contextual effects. The authors propose five points for evaluating behavioral genetic studies' conceptualization of environment and use those points to evaluate three exemplary recent studies.
Incorporating Experimental Design and Error Into Coalescent/Mutation Models of Population History
Authors: Knudsen Bjarne , Miyamoto Michael M
Published: June 2007

Coalescent theory provides a powerful framework for estimating the evolutionary, demographic, and genetic parameters of a population from a small sample of individuals. Current coalescent models have largely focused on population genetic factors (e.g., mutation, population growth, and migration) rather than on the effects of experimental design and error. This study develops a new coalescent/mutation model that accounts for unobserved polymorphisms due to missing data, sequence errors, and multiple reads for diploid individuals. The importance of accommodating these effects of experimental design and error is illustrated with evolutionary simulations and a real data set from a population of the California sea hare. In particular, a failure to account for sequence errors can lead to overestimated mutation rates, inflated coalescent times, and inappropriate conclusions about the population. This current model can now serve as a starting point for the development of newer models with additional experimental and population genetic factors. It is currently implemented as a maximum-likelihood method, but this model may also serve as the basis for the development of Bayesian approaches that incorporate experimental design and error.
Cytotype Regulation by TelomericPElements inDrosophila melanogaster: Interactions WithPElements From M′ Strains
Authors: Simmons Michael J , Niemi Jarad B , Ryzek Don-Felix , Lamour Cecile , Goodman Joseph W , Kraszkiewicz Wojciech , Wolff Ryan
Published: June 2007

P strains of Drosophila are distinguished from M strains by having P elements in their genomes and also by having the P cytotype, a maternally inherited condition that strongly represses P-element-induced hybrid dysgenesis. The P cytotype is associated with P elements inserted near the left telomere of the X chromosome. Repression by the telomeric P elements TP5 and TP6 is significantly enhanced when these elements are crossed into M′ strains, which, like P strains, carry P elements, but have little or no ability to repress dysgenesis. The telomeric and M′ P elements must coexist in females for this enhanced repression ability to develop. However, once established, it is transmitted maternally to the immediate offspring independently of the telomeric P elements themselves. Females that carry a telomeric P element but that do not carry M′ P elements may also transmit an ability to repress dysgenesis to their offspring independently of the telomeric P element. Cytotype regulation therefore involves a maternally transmissible product of telomeric P elements that can interact synergistically with products from paternally inherited M′ P elements. This synergism between TP and M′ P elements also appears to persist for at least one generation after the TP has been removed from the genotype.
New Candidate Genes for Sex-Comb Divergence BetweenDrosophila mauritianaandDrosophila simulans
Authors: Graze Rita M , Barmina Olga , Tufts Daniel , Naderi Elena , Harmon Kristy L , Persianinova Maria , Nuzhdin Sergey V
Published: June 2007

A large-effect QTL for divergence in sex-comb tooth number between Drosophila simulans and D. mauritiana was previously mapped to 73A–84AB. Here we identify genes that are likely contributors to this divergence. We first improved the mapping resolution in the 73A–84AB region using 12 introgression lines and 62 recombinant nearly isogenic lines. To further narrow the list of candidate genes, we assayed leg-specific expression and identified genes with transcript-level evolution consistent with a potential role in sex-comb divergence. Sex combs are formed on the prothoracic (front) legs, but not on the mesothoracic (middle) legs of Drosophila males. We extracted RNA from the prothoracic and mesothoracic pupal legs of two species to determine which of the genes expressed differently between leg types were also divergent for gene expression. Two good functional candidate genes, Scr and dsx, are located in one of our fine-scale QTL regions. In addition, three previously uncharacterized genes (CG15186, CG2016, and CG2791) emerged as new candidates. These genes are located in regions strongly associated with sex-comb tooth number differences and are expressed differently between leg tissues and between species. Further supporting the potential involvement of these genes in sex-comb divergence, we found a significant difference in sex-comb tooth number between co-isogenic D. melanogaster lines with and without P-element insertions at CG2791.
Testing the Extreme Value Domain of Attraction for Distributions of Beneficial Fitness Effects
Authors: Beisel Craig J , Rokyta Darin R , Wichman Holly A , Joyce Paul
Published: June 2007

In modeling evolutionary genetics, it is often assumed that mutational effects are assigned according to a continuous probability distribution, and multiple distributions have been used with varying degrees of justification. For mutations with beneficial effects, the distribution currently favored is the exponential distribution, in part because it can be justified in terms of extreme value theory, since beneficial mutations should have fitnesses in the extreme right tail of the fitness distribution. While the appeal to extreme value theory seems justified, the exponential distribution is but one of three possible limiting forms for tail distributions, with the other two loosely corresponding to distributions with right-truncated tails and those with heavy tails. We describe a likelihood-ratio framework for analyzing the fitness effects of beneficial mutations, focusing on testing the null hypothesis that the distribution is exponential. We also describe how to account for missing the smallest-effect mutations, which are often difficult to identify experimentally. This technique makes it possible to apply the test to gain-of-function mutations, where the ancestral genotype is unable to grow under the selective conditions. We also describe how to pool data across experiments, since we expect few possible beneficial mutations in any particular experiment.
A Fitness Cost Associated With the Antibiotic Resistance Enzyme SME-1 β-Lactamase
Authors: Marciano David C , Karkouti Omid Y , Palzkill Timothy
Published: June 2007

The blaTEM-1 β-lactamase gene has become widespread due to the selective pressure of β-lactam use and its stable maintenance on transferable DNA elements. In contrast, blaSME-1 is rarely isolated and is confined to the chromosome of carbapenem-resistant Serratia marcescens strains. Dissemination of blaSME-1 via transfer to a mobile DNA element could hinder the use of carbapenems. In this study, blaSME-1 was determined to impart a fitness cost upon Escherichia coli in multiple genetic contexts and assays. Genetic screens and designed SME-1 mutants were utilized to identify the source of this fitness cost. These experiments established that the SME-1 protein was required for the fitness cost but also that the enzyme activity of SME-1 was not associated with the fitness cost. The genetic screens suggested that the SME-1 signal sequence was involved in the fitness cost. Consistent with these findings, exchange of the SME-1 signal sequence for the TEM-1 signal sequence alleviated the fitness cost while replacing the TEM-1 signal sequence with the SME-1 signal sequence imparted a fitness cost to TEM-1 β-lactamase. Taken together, these results suggest that fitness costs associated with some β-lactamases may limit their dissemination.
On the Utility of Linkage Disequilibrium as a Statistic for Identifying Targets of Positive Selection in Nonequilibrium Populations
Authors: Jensen Jeffrey D , Thornton Kevin R , Bustamante Carlos D , Aquadro Charles F
Published: June 2007

A critically important challenge in empirical population genetics is distinguishing neutral nonequilibrium processes from selective forces that produce similar patterns of variation. We here examine the extent to which linkage disequilibrium (i.e., nonrandom associations between markers) improves this discrimination. We show that patterns of linkage disequilibrium recently proposed to be unique to hitchhiking models are replicated under nonequilibrium neutral models. We also demonstrate that jointly considering spatial patterns of association among variants alongside the site-frequency spectrum is nonetheless of value. Through a comparison of models of equilibrium neutrality, nonequilibrium neutrality, equilibrium hitchhiking, nonequilibrium hitchhiking, and recurrent hitchhiking, we evaluate a linkage disequilibrium (LD) statistic (ωmax) that appears to have power to identify regions recently shaped by positive selection. Most notably, for demographic parameters relevant to non-African populations of Drosophila melanogaster, we demonstrate that selected loci are distinguishable from neutral loci using this statistic.