bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepcidin levels in diabetes mellitus and polycystic ovary syndrome
Authors: Sam A. H. , Busbridge M. , Amin A. , Webber L. , White D. , Franks S. , Martin N. M. , Sleeth M. , Ismail N. A. , Daud N. Mat , Papamargaritis D. , Le Roux C. W. , Chapman R. S. , Frost G. , Bloom S. R. , Murphy K. G. 
Published: June 2013

AbstractAimIncreased body iron is associated with insulin resistance. Hepcidin is the key hormone that negatively regulates iron homeostasis. We hypothesized that individuals with insulin resistance have inadequate hepcidin levels for their iron load.MethodsSerum concentrations of the active form of hepcidin (hepcidin‐25) and hepcidin:ferritin ratio were evaluated in participants with Type 2 diabetes (n = 33, control subjects matched for age, gender and BMI, n = 33) and participants with polycystic ovary syndrome (n = 27, control subjects matched for age and BMI, n = 16). To investigate whether any changes observed were associated with insulin resistance rather than insulin deficiency or hyperglycaemia per se, the same measurements were made in participants with Type 1 diabetes (n = 28, control subjects matched for age, gender and BMI, n = 30). Finally, the relationship between homeostasis model assessment of insulin resistance and serum hepcidin:ferritin ratio was explored in overweight or obese participants without diabetes (n = 16).ResultsParticipants with Type 2 diabetes had significantly lower hepcidin and hepcidin:ferritin ratio than control subjects (P < 0.05 and P < 0.01, respectively). Participants with polycystic ovary syndrome had a significantly lower hepcidin:ferritin ratio than control subjects (P < 0.05). There was no significant difference in hepcidin or hepcidin:ferritin ratio between participants with Type 1 diabetes and control subjects (P = 0.88 and P = 0.94). Serum hepcidin:ferritin ratio inversely correlated with homeostasis model assessment of insulin resistance (r = –0.59, P < 0.05).ConclusionInsulin resistance, but not insulin deficiency or hyperglycaemia per se, is associated with inadequate hepcidin levels. Reduced hepcidin concentrations may cause increased body iron stores in insulin‐resistant states.
Waist circumference is genetically correlated with incident Type 2 diabetes in Mexican‐American families
Authors: Mamtani M. , Kulkarni H. , Dyer T. D. , Almasy L. , Mahaney M. C. , Duggirala R. , Comuzzie A. G. , Blangero J. , Curran J. E. 
Published: June 2013

AbstractAimsWe aimed to determine the genetic and environmental correlation between various anthropometric indexes and incident Type 2 diabetes with a focus on waist circumference.MethodsWe used the data on extended Mexican‐American families (808 subjects, 7617.92 person‐years follow‐up) from the San Antonio Family Heart Study and estimated the genetic and environmental correlations of 16 anthropometric indexes with the genetic liability of incident Type 2 diabetes. We performed bivariate trait analyses using the solar software package.ResultsAll 16 anthropometric indexes were significantly heritable (range of heritabilities 0.24–0.99). Thirteen indexes were found to have significant environmental correlation with the liability of incident Type 2 diabetes. In contrast, only anthropometric indexes consisting of waist circumference (waist circumference, waist–hip ratio and waist–height ratio) were significantly genetically correlated (genetic correlation coefficients: 0.45, 0.55 and 0.44, respectively) with the liability of incident Type 2 diabetes. We did not observe such a correlation for BMI.ConclusionsWaist circumference as a predictor of future Type 2 diabetes is supported by the finding that they share common genetic influences.
Effect of grazing intensity on the interaction between Shijimiaeoides divinus asonis (Matsumura, 1929) and its attendant ants
Authors: Murata Kouhei , Matsuura Asana 
Published: June 2013

AbstractThis study was carried out in the natural herbaceous grassland of Mt. Aso, which had been almost completely grazed, and which is subjected to routine grassland burning every spring (February or March) to conserve Shijimiaeoides divinus asonis (Matsumura, 1929). We clarify that ants protect the larvae of this butterfly and evaluate the effects of grazing intensity on the attendant ant population. The results obtained are summarized as follows: (i) Five species of attendant ant were identified, with the dominant species being Formica japonica (Motschulsky, 1866) and Camponotus japonicus (Mayr, 1866). (ii) The number of attendant ants decreased at night time; however, only one or two ants attended the larva until the following morning. (iii) Ten species of insect excluding ants and three species of spiders that approached the larva were recorded on the larval host‐plant. Formica japonica and C. japonicus fought off most newcomers of other insects including the natural enemies of these butterfly larvae. (iv) The number of ants in this butterfly habitat under regular grazing intensity was significantly higher than during low grazing intensity and non‐grazing periods. (v) A positive correlation was found between the number of attendant ants and the number of butterfly larvae on the host‐plant. We concluded that the interaction between this butterfly and attendant ants is one of facultative mutualism because the attendant ants protect the butterfly larva. Therefore, the numbers of this butterfly species may decrease if the number of attendant ants decreases due to the cessation of pasturage.
Consequences of proline‐to‐alanine substitutions for the stability and refolding of onconase
Authors: Hacke Mandy , Gruber Tobias , Schulenburg Cindy , Balbach Jochen , Arnold Ulrich 
Published: June 2013

Peptidyl‐prolyl isomerization reactions can make for rate‐limiting steps in protein folding due to their high activation energy. Onconase, an unusually stable ribonuclease A homologue from the Northern leopard frog, contains fourtransproline residues in its native state. During the refolding from its guanidine hydrochloride unfolded state, which includes the formation of a folding intermediate, the slowest of the three phases has earlier been attributed to acis‐to‐transpeptidyl‐prolyl isomerization reaction. We thus substituted all four proline residues individually by alanine and investigated the effect of the amino acid substitutions on the folding and stability of the onconase variants. All onconase variants proved to adopt a tertiary structure comparable with that of the wild‐type protein. Although the slow phase was not eliminated for any of the variants, the P43A substitution resulted in an increase in the rate constant of the fast folding phase, i.e. a faster formation of the folding intermediate. This variant also exhibits a significant increase in thermodynamic stability. As residue 43 belongs to those residues that are protected from hydrogen exchange with the solvent in the folding intermediate, the increase in the rate constant and stability of the P43A variant emphasizes the importance of the intermediate for the folding of onconase.EnzymesOnconase (EC 3.1.27.5)
Morphology of biogenic iron oxides records microbial physiology and environmental conditions: toward interpreting iron microfossils
Authors: Krepski S. T. , Emerson D. , Hredzak‐Showalter P. L. , Luther G. W. , Chan C. S. 
Published: June 2013

AbstractDespite the abundance of Fe and its significance in Earth history, there are no established robust biosignatures for Fe(II)‐oxidizing micro‐organisms. This limits our ability to piece together the history of Fe biogeochemical cycling and, in particular, to determine whether Fe(II)‐oxidizers played a role in depositing ancient iron formations. A promising candidate for Fe(II)‐oxidizer biosignatures is the distinctive morphology and texture of extracellular Fe(III)‐oxyhydroxide stalks produced by mat‐forming microaerophilic Fe(II)‐oxidizing micro‐organisms. To establish the stalk morphology as a biosignature, morphologic parameters must be quantified and linked to the microaerophilic Fe(II)‐oxidizing metabolism and environmental conditions. Toward this end, we studied an extant model organism, the marine stalk‐forming Fe(II)‐oxidizing bacterium, Mariprofundus ferrooxydans PV‐1. We grew cultures in flat glass microslide chambers, with FeS substrate, creating opposing oxygen/Fe(II) concentration gradients. We used solid‐state voltammetric microelectrodes to measure chemical gradients in situ while using light microscopy to image microbial growth, motility, and mineral formation. In low‐oxygen (2.7–28 μm) zones of redox gradients, the bacteria converge into a narrow (100 μm–1 mm) growth band. As cells oxidize Fe(II), they deposit Fe(III)‐oxyhydroxide stalks in this band; the stalks orient directionally, elongating toward higher oxygen concentrations. M. ferrooxydans stalks display a narrow range of widths and uniquely biogenic branching patterns, which result from cell division. Together with filament composition, these features (width, branching, and directional orientation) form a physical record unique to microaerophilic Fe(II)‐oxidizer physiology; therefore, stalk morphology is a biosignature, as well as an indicator of local oxygen concentration at the time of formation. Observations of filamentous Fe(III)‐oxyhydroxide microfossils from a ~170 Ma marine Fe‐Si hydrothermal deposit show that these morphological characteristics can be preserved in the microfossil record. This study demonstrates the potential of morphological biosignatures to reveal microbiology and environmental chemistry associated with geologic iron formation depositional processes.
Identification of KIT activating mutations in paediatric solitary mastocytoma
Authors: Ma Deqin , Stence Aaron A , Bossler Aaron B , Hackman Jason R , Bellizzi Andrew M 
Published: June 2013

AimsMastocytosis is an abnormal mast cell proliferation involving one or more organs, in particular the skin and bone marrow. In children, disease is usually limited to the skin, with three distinct clinical presentations: urticaria pigmentosa, diffuse cutaneous mastocytosis and solitary mastocytoma. Although the KIT D816V mutation is typically found in adult‐onset mastocytosis, it is less commonly seen in childhood‐onset mastocytosis, and the frequency of KIT mutations in paediatric solitary mastocytoma is poorly documented.Methods and resultsIn this study we analysed KIT exons 8, 9, 11, 13 and 17 in nine cases of paediatric solitary mastocytoma using a laboratory‐developed Sanger sequencing assay. A KIT mutation was identified in six cases (67%), including three with the D816V mutation typical of adult‐onset disease, and another three with an internal tandem duplication (p.A502_Y503dup) in exon 9, previously described in gastrointestinal stromal tumour.ConclusionsPaediatric solitary mastocytoma is frequently associated with KIT activating mutations, in keeping with a clonal process. KIT mutational status appears insufficient to explain the divergent biology of childhood and adult‐onset disease.
The effect of medicated, sugar‐free chewing gum on plaque and clinical parameters of gingival inflammation: a systematic review
Authors: Keukenmeester RS , Slot DE , Putt MS , Van der Weijden GA 
Published: June 2013

AbstractObjectiveThis study aimed to systematically review the present literature to establish the clinical effect of medicated, sugar‐free chewing gum on plaque indices and parameters of gingival inflammation.Materials and methodsMEDLINE–PubMed, Cochrane CENTRAL and EMBASE databases were searched up to April 2012 to identify appropriate studies. Included studies used an intervention of medicated, sugar‐free chewing gum containing antimicrobial agents or herbal extracts compared with a control gum. Plaque and gingivitis scores were selected as outcome variables.ResultsIndependent screening of 594 unique titles and abstracts identified 10 non‐brushing and four brushing studies that met the eligibility criteria. Means and standard deviations were extracted. A sufficient number of studies evaluated chlorhexidine gum to perform a meta‐analysis. Although this review provides evidence for the comparative effectiveness of chewing gums containing various ingredients, the results must be weighed carefully against the methods that were used to assess their outcomes.ConclusionMost of the chewing gums with antimicrobial agents or herbal extracts were shown to have a positive effect with respect to plaque and gingivitis scores. The most compelling evidence was provided for chewing gum containing chlorhexidine. Meta‐analysis and individual results indicate a beneficial effect of chlorhexidine on plaque inhibition. However, GRADE evidence profile shows that the recommendation to use CHX‐gum to reduce plaque scores in the absence of brushing is considered to be ‘weak’. Other ingredients with positive outcomes on plaque scores are eucalyptus, acacia, funoran, Pycnogenol and mastic. Limited data with respect to gingivitis scores were available, and the following agents showed a positive effect: magnolia, eucalyptus and CHX.
Joint optimization of pricing and planning decisions in divergent supply chain
Authors: Guajardo Mario , Kylinger Martin , Rönnqvist Mikael 
Published: June 2013

AbstractIn divergent supply chains, such as in the oil industry, processing raw materials results in an outflow of multiple products. Final products are stored at international depots, from where they are ready to be shipped to the markets. Even if one company controls the entire chain, when production and sales organizations are decoupled, a relevant problem is to determine the internal prices of products at depots for achieving coordination. We propose an optimization model involving pricing and production decisions, and several constraints commonly used in divergent chains. In our approach, the producer incorporates the sellers’ behavior by expressing demand as a function of the internal price. As a result, our model serves as a coordination mechanism in trying to get an overall coordinated integrated solution in a decoupled reality. Numerical examples in single and multiple periods problems show the advantages of our approach over cost‐based methods.
A heuristic and an exact method for the gate matrix connection cost minimization problem
Authors: De Giovanni L. , Massi G. , Pezzella F. , Pfetsch M.E. , Rinaldi G. , Ventura P. 
Published: June 2013

AbstractIn many applications, a sequencing of patterns (electronic circuit nodes, cutting patterns, product orders, etc.) has to be found in order to optimize some given objective function, giving rise to the so‐called open stack problems. We focus on a problem related to the optimization of gate matrix layouts: electronic circuits are obtained by connecting gates and one seeks a gate layout permutation that minimizes connection costs under restrictions on the circuit area. In the literature, the connection costs and circuit area are also known as time of open stacks and maximum number of open stacks, respectively. We propose a genetic algorithm providing heuristic solutions and a branch‐and‐cut algorithm based on a new linear integer programming formulation that represents, to the best of our knowledge, the first exact method proposed in the literature. The algorithms have been tested on real instances and on data sets from the literature. The computational results give evidence that the proposed methods provide solutions that improve the ones found by the approaches presented in the literature.
Immunogenicity of Injectable Collagen Implants
Authors: SELLEM PHILIPPE H. , CARANZAN FRANCOIS R. , BENE MARIE C. , FAURE GILBERT C. 
Published: June 2013

AbstractThe presence of antibodies to bovine and human collagens used in injectable collagen implants (ICI) was investigated in 103 normal sera. Significant levels of spontaneous nonprecipitin antibodies were observed, suggesting that immunization to ICI compounds may preexist even in the absence of connective tissue disease.
Geriatric Patient Care by U.S. Pharmacists in Healthcare Teams: Systematic Review and Meta‐Analyses
Authors: Lee Jeannie K. , Slack Marion K. , Martin Jennifer , Ehrman Clara , Chisholm‐Burns Marie 
Published: June 2013

ObjectivesTo conduct a systematic review and meta‐analyses to examine the effects of pharmacists' care on geriatric patient‐oriented health outcomes in the United States (U.S.).DesignStudies examining U.S. pharmacists' patient care services from inception of the databases through July 2012 were searched. The databases searched include PubMed/MEDLINE, Ovid/MEDLINE, ABI/INFORM, Health Business Fulltext Elite, Academic Search Complete, International Pharmaceutical Abstracts, PsycINFO, Cochrane Database, and Clinical Trials.gov. Studies reporting pharmacists' intervention for geriatric patients, comparison groups, and patient‐oriented outcomes were assessed. Dual review for inclusion and data extraction were performed.SettingUniversity of Arizona College of Pharmacy.MeasurementsStudy and participant characteristics, pharmacist intervention, and outcomes with data for meta‐analyses were collected. A forest plot was constructed to obtain a pooled standardized mean difference using a random effects model.ResultsOne hundred fifty‐two articles were reviewed, with 20 resulting studies included in the final meta‐analyses. Study sample size ranged from 36 to 4,218, with mean age of subjects being 65 and older. The studies were most frequently conducted in ambulatory care clinics, followed by inpatient settings; the majority focused on multiple diseases and conditions. Pharmacist activities varied widely, with technical interventions used most often. Favorable results were found in all outcome categories, and meta‐analyses conducted for therapeutic, safety, hospitalization, and adherence were significant (P < .001), favoring pharmacist care over comparison. Some identifiable variability existed between included studies.ConclusionPharmacist intervention has favorable effects on therapeutic, safety, hospitalization, and adherence outcomes in older adults. Pharmacists should be involved in team‐based care of older adults.
A novel anticonvulsant modulates voltage‐gated sodium channel inactivation and prevents kindling‐induced seizures
Authors: Ashraf Muhammad N. , Gavrilovici Cezar , Ali Shah Syed U. , Shaheen Farzana , Choudhary Muhammad I. , Rahman Atta‐ur , Fahnestock Margaret , Simjee Shabana U. , Poulter Michael O. 
Published: June 2013

AbstractHere, we explore the mechanism of action of isoxylitone (ISOX), a molecule discovered in the plant Delphinium denudatum, which has been shown to have anticonvulsant properties. Patch‐clamp electrophysiology assayed the activity of ISOX on voltage‐gated sodium channels (VGSCs) in both cultured neurons and brain slices isolated from controls and rats with experimental epilepsy (kindling model). Quantitative transcription polymerase chain reaction (qRT‐PCR) (QPCR) assessed brain‐derived neurotrophic factor (BDNF) mRNA expression in kindled rats, and kindled rats treated with ISOX. ISOX suppressed sodium current (INa) showing an IC50 value of 185 nM in cultured neurons. ISOX significantly slowed the recovery from inactivation (ISOX τ = 18.7 ms; Control τ = 9.4 ms; p < 0.001). ISOX also enhanced the development of inactivation by shifting the Boltzmann curve to more hyperpolarized potentials by −11.2 mV (p < 0.05). In naive and electrically kindled cortical neurons, the IC50 for sodium current block was identical to that found in cultured neurons. ISOX prevented kindled stage 5 seizures and decreased the enhanced BDNF mRNA expression that is normally associated with kindling (p < 0.05). Overall, our data show that ISOX is a potent inhibitor of VGSCs that stabilizes steady‐state inactivation while slowing recovery and enhancing inactivation development. Like many other sodium channel blocker anti‐epileptic drugs, the suppression of BDNF mRNA expression that usually occurs with kindling is likely a secondary outcome that nevertheless would suppress epileptogenesis. These data show a new class of anti‐seizure compound that inhibits sodium channel function and prevents the development of epileptic seizures.
image
Isoxylitones, isolated from Delphinium denudatum root prevent seizure induction. Activity was tested on voltage‐gated sodium channels (VGSCs) in both cultured neurons and brain slices isolated from controls and rats with experimental epilepsy (kindling model). Isoxylitones enhanced sodium channel inactivation with an IC50 of about 200 nM. Our findings suggest isoxylitones as a potential novel anticonvulsant agent.
Radiolabeling and in vitro /in vivo evaluation of N‐(1‐adamantyl)‐8‐methoxy‐4‐oxo‐1‐phenyl‐1,4‐dihydroquinoline‐3‐carboxamide as a PET probe for imaging cannabinoid type 2 receptor
Authors: Mu Linjing , Bieri Daniel , Slavik Roger , Drandarov Konstantin , Müller Adrienne , Čermak Stjepko , Weber Markus , Schibli Roger , Krämer Stefanie D. , Ametamey Simon M. 
Published: June 2013

AbstractThe cannabinoid type 2 (CB2) receptor plays an important role in neuroinflammatory and neurodegenerative diseases such as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease and is therefore a very promising target for therapeutic approaches as well as for imaging. Based on the literature, we identified one 4‐oxoquinoline derivative (designated KD2) as the lead structure. It was synthesized, radiolabeled and evaluated as a potential imaging tracer for CB2. [11C]KD2 was obtained in 99% radiochemical purity. Moderate blood–brain barrier (BBB) passage was predicted for KD2 from an in vitro transport assay with P‐glycoprotein‐transfected Madin Darby canine kidney cells. No efflux of KD2 by P‐glycoprotein was detected. In vitro autoradiography of rat and mouse spleen slices demonstrated that [11C]KD2 exhibits high specific binding towards CB2. High spleen uptake of [11C]KD2 was observed in dynamic positron emission tomography (PET) studies with Wistar rats and its specificity was confirmed by displacement study with a selective CB2 agonist, GW405833. A pilot autoradiography study with post‐mortem spinal cord slices from amyotrophic lateral sclerosis (ALS) patients with [11C]KD2 suggested the presence of CB2 receptors under disease conditions. Specificity of [11C]KD2 binding could also be demonstrated on these human tissues. In conclusion, [11C]KD2 shows good in vitro and in vivo properties as a potential PET tracer for CB2.
image
The cannabinoid type 2 receptor (CB2) plays an important role in neuroinflammatory and neuro–degenerative diseases. [11C]KD2, a new CB2 radioligand, exhibits selectivity towards CB2 receptor in vitro and in vivo in rat. A pilot autoradiography study with spinal cord slices from amyotrophic lateral sclerosis patients with [11C]KD2 suggested the presence of CB2 under disease conditions (Figure). Selective CB2 agonist, GW405833.