bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

AbstractIn 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.
1-Lithio-1,3-dienes: Useful Building Blocks for Cyclic Compounds
Authors: Xi Zhenfeng 
Published: June 2007

Abstract
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

Abstract
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 (&lt; 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

Abstract
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

Abstract
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

Abstract
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.
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.
Incorporating Experimental Design and Error Into Coalescent/Mutation Models of Population History
Authors: Knudsen Bjarne , Miyamoto Michael M 
Published: June 2007

Abstract
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

AbstractP 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

AbstractA 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

AbstractIn 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.