bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitamin D Deficiency Promotes Skeletal Muscle Hypersensitivity and Sensory Hyperinnervation
Authors: Tague Sarah E. , Clarke Gwenaëlle L. , Winter Michelle K. , McCarson Kenneth E. , Wright Douglas E. , Smith Peter G.
Published: September 2011

Musculoskeletal pain affects nearly half of all adults, most of whom are vitamin D deficient. Previous findings demonstrated that putative nociceptors (“pain-sensing” nerves) express vitamin D receptors (VDRs), suggesting responsiveness to 1,25-dihydroxyvitamin D. In the present study, rats receiving vitamin D-deficient diets for 2–4 weeks showed mechanical deep muscle hypersensitivity, but not cutaneous hypersensitivity. Muscle hypersensitivity was accompanied by balance deficits and occurred before onset of overt muscle or bone pathology. Hypersensitivity was not due to hypocalcemia and was actually accelerated by increased dietary calcium. Morphometry of skeletal muscle innervation showed increased numbers of presumptive nociceptor axons (peripherin-positive axons containing calcitonin gene-related peptide), without changes in sympathetic or skeletal muscle motor innervation. Similarly, there was no change in epidermal innervation. In culture, sensory neurons displayed enriched VDR expression in growth cones, and sprouting was regulated by VDR-mediated rapid response signaling pathways, while sympathetic outgrowth was not affected by different concentrations of 1,25-dihydroxyvitamin D. These findings indicate that vitamin D deficiency can lead to selective alterations in target innervation, resulting in presumptive nociceptor hyperinnervation of skeletal muscle, which in turn is likely to contribute to muscular hypersensitivity and pain.
Sperm competition differentially affects swimming velocity and size of spermatozoa from closely related muroid rodents: head first
Authors: Gómez Montoto Laura , Varea Sánchez María , Tourmente Maximiliano , Martín-Coello Juan , Luque-Larena Juan José , Gomendio Montserrat , Roldan Eduardo R S
Published: September 2011

Sperm competition favours an increase in sperm swimming velocity that maximises the chances that sperm will reach the ova before rival sperm and fertilise. Comparative studies have shown that the increase in sperm swimming speed is associated with an increase in total sperm size. However, it is not known which are the first evolutionary steps that lead to increases in sperm swimming velocity. Using a group of closely related muroid rodents that differ in levels of sperm competition, we here test the hypothesis that subtle changes in sperm design may represent early evolutionary changes that could make sperm swim faster. Our findings show that as sperm competition increases so does sperm swimming speed. Sperm swimming velocity is associated with the size of all sperm components. However, levels of sperm competition are only related to an increase in sperm head area. Such increase is a consequence of an increase in the length of the sperm head, and also of the presence of an apical hook in some of the species studied. These findings suggest that the presence of a hook may modify the sperm head in such a way that would help sperm swim faster and may also be advantageous if sperm with larger heads are better able to attach to the epithelial cells lining the lower isthmus of the oviduct where sperm remain quiescent before the final race to reach the site of fertilisation.
A Method for Inferring the Rate of Occurrence and Fitness Effects of Advantageous Mutations
Authors: Schneider Adrian , Charlesworth Brian , Eyre-Walker Adam , Keightley Peter D
Published: September 2011

The distribution of fitness effects (DFE) of new mutations is of fundamental importance in evolutionary genetics. Recently, methods have been developed for inferring the DFE that use information from the allele frequency distributions of putatively neutral and selected nucleotide polymorphic variants in a population sample. Here, we extend an existing maximum-likelihood method that estimates the DFE under the assumption that mutational effects are unconditionally deleterious, by including a fraction of positively selected mutations. We allow one or more classes of positive selection coefficients in the model and estimate both the fraction of mutations that are advantageous and the strength of selection acting on them. We show by simulations that the method is capable of recovering the parameters of the DFE under a range of conditions. We apply the method to two data sets on multiple protein-coding genes from African populations of Drosophila melanogaster. We use a probabilistic reconstruction of the ancestral states of the polymorphic sites to distinguish between derived and ancestral states at polymorphic nucleotide sites. In both data sets, we see a significant improvement in the fit when a category of positively selected amino acid mutations is included, but no further improvement if additional categories are added. We estimate that between 1% and 2% of new nonsynonymous mutations in D. melanogaster are positively selected, with a scaled selection coefficient representing the product of the effective population size, Ne, and the strength of selection on heterozygous carriers of ∼2.5.
Quantifying the Variation in the Effective Population Size Within a Genome
Authors: Gossmann Toni I , Woolfit Megan , Eyre-Walker Adam
Published: September 2011

The effective population size (Ne) is one of the most fundamental parameters in population genetics. It is thought to vary across the genome as a consequence of differences in the rate of recombination and the density of selected sites due to the processes of genetic hitchhiking and background selection. Although it is known that there is intragenomic variation in the effective population size in some species, it is not known whether this is widespread or how much variation in the effective population size there is. Here, we test whether the effective population size varies across the genome, between protein-coding genes, in 10 eukaryotic species by considering whether there is significant variation in neutral diversity, taking into account differences in the mutation rate between loci by using the divergence between species. In most species we find significant evidence of variation. We investigate whether the variation in Ne is correlated to recombination rate and the density of selected sites in four species, for which these data are available. We find that Ne is positively correlated to recombination rate in one species, Drosophila melanogaster, and negatively correlated to a measure of the density of selected sites in two others, humans and Arabidopsis thaliana. However, much of the variation remains unexplained. We use a hierarchical Bayesian analysis to quantify the amount of variation in the effective population size and show that it is quite modest in all species—most genes have an Ne that is within a few fold of all other genes. Nonetheless we show that this modest variation in Ne is sufficient to cause significant differences in the efficiency of natural selection across the genome, by demonstrating that the ratio of the number of nonsynonymous to synonymous polymorphisms is significantly correlated to synonymous diversity and estimates of Ne, even taking into account the obvious nonindependence between these measures.
Statistical Korovkin-type theory for matrix-valued functions
Authors: Duman Oktay , Erkuş-Duman Esra
Published: September 2011

In this paper, using the notion ofA-statistical convergence from the summability theory, we obtain a Korovkin-type theorem for the approximation by means of matrixvalued linear positive operators. We show that our theorem is more applicable than the result introduced by S. Serra-Capizzano [A Korovkin based approximation of multilevel Toeplitz matrices (with rectangular unstructured blocks) via multilevel trigonometric matrix spaces,SIAM J. Numer. Anal.,36(1999), 1831–1857]. Furthermore, we compute theA-statistical rates of our approximation.
Successful Treatment of Sulfasalazine‐Induced DRESS Syndrome with Corticosteroids and N‐Acetylcysteine
Authors: Jose Joyce , Klein Robin
Published: September 2011

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, severe drug hypersensitivity syndrome characterized by fever, rash, hematologic abnormalities, and systemic involvement. The pathogenesis of DRESS is unclear, but it is thought that the offending drug induces an immunemediated hypersensitivity reaction through defects in metabolism. Severe cases of DRESS often require aggressive treatment; however, current pharmacologic treatment options are limited. We describe a 66‐year‐old woman who presented with fever and rash 3 weeks after starting sulfasalazine treatment for rheumatoid arthritis. Investigation revealed diffuse lymphadenopathy, leukocytosis, eosinophilia, and hepatitis. She was diagnosed with DRESS syndrome, sulfasalazine was discontinued, and she was treated with methylprednisolone. Her condition deteriorated, and she developed severe acute liver failure prompting evaluation for liver transplantation. Corticosteroid treatment was escalated to high‐dose methylprednisolone, and N‐acetylcysteine was started, which prompted improvement in her symptoms and liver function. To our knowledge, this is the first case report to describe the safe and successful use of corticosteroids and N‐acetylcysteine to treat sulfasalazine‐induced DRESS syndrome. Given the potential morbidity and mortality of DRESS syndrome, effective treatment alternatives for severe cases are needed. N‐Acetylcysteine may be a safe adjunct to corticosteroid therapy for severe cases of sulfasalazine‐induced DRESS syndrome.
New and Emerging Anticoagulant Therapy for Atrial Fibrillation and Acute Coronary Syndrome
Authors: Davis Estella M. , Packard Kathleen A. , Knezevich Jon T. , Campbell Jennifer A.
Published: September 2011

Thrombosis is an underlying cause of many cardiovascular disorders, and generation of thrombi in the arterial circulation can lead to unstable angina, myocardial infarction, or ischemic stroke. Antithrombotic therapy is widely used, with proven benefit to prevent ischemic stroke and thromboembolic events in patients with atrial fibrillation (AF) or to prevent further ischemic complications in patients with acute coronary syndrome (ACS). Traditional anticoagulants (including unfractionated heparin, low‐molecular‐weight heparin, and warfarin) and antiplatelet agents (including aspirin, clopidogrel, and prasugrel) are typically used for these indications. Limitations to their use include variable pharmacokinetic and pharmacodynamic profiles, inability to inhibit fibrin‐bound thrombin, risk of heparin‐induced thrombocytopenia, delayed onset of action, numerous drug interactions, need for substantial laboratory monitoring and dosage titrations, hyporesponsiveness or resistance, hypersensitivity, adverse events, and bleeding. To overcome some of the limitations of traditional agents, new antithrombotic agents under development are highly selective for specific coagulation factors blocking the synthesis of thrombin. Clinicians must have an understanding of the new anticoagulants to aid in the selection of appropriate therapies for patients. We describe the most relevant phases II and III clinical trials that evaluated several recent emerging anticoagulant drugs for use in patients with AF or ACS. The advantages of many new agents include predictable pharmacodynamic response and pharmacokinetic parameters, allowing for fixed oral dosing with no need for laboratory monitoring. For patients with AF, dabigatran is already approved for the prevention of stroke and systemic embolism, rivaroxaban appears to be an effective alternative to warfarin in high‐risk patients, and apixaban may also be an effective alternative to aspirin in patients unable to take warfarin. Otamixaban shows promise as an intravenous alternative for patients with ACS in the acute care setting. Likewise, rivaroxaban, dabigatran, and darexaban with or without dual antiplatelet therapy may be beneficial for secondary prevention of ischemic events in patients with ACS.
New Area Studies and Languages on the Move
Authors: Tsu Jing
Published: September 2011

In 1909 Wu Zhihui, a proponent of esperanto and well-known anarchist of Twentieth-Century China, predicted the future of global languages. Though the nationalization of the Chinese language was still pending, Wu expressed concern not for its imminent standardization but for its eventual global viability. The outlook was not rosy:

Not only is the Chinese language not phoneticized, it is also not easy to typeset or index. This is a tremendous obstacle to the dissemination of civilized modernization and the governance of all things…. Looking up Chinese characters takes great effort indeed. Regardless of the index system and classification scheme, it is very difficult to memorize them. Moreover, there are too many characters…. Western writing has one great advantage, which became clear as the greatest disadvantage of the Chinese language only with the advancement of machine technology. A typewriter can be used with Western scripts but not with the Chinese language…. Sooner or later the Chinese script has to be abolished.

(51, 36, 37, 52; my trans.)
The Right to Imagine: Reading in Community with People and Stories / Gente y Cuentos
Authors: Schwartz Marcy
Published: September 2011

In Córdoba, Argentina, a library of books once banned by the military junta's censors (1976–83) now resides at a center called the Espacio para la Memoria (“Space for Memory”). The site, where prisoners were once held and tortured, houses workshops inviting schoolchildren to think about this terrifying period in their history. Under the junta, even children's books were banned, and after reading a few of these titles with the children who visit the center, the workshop leaders ask them why they think the books were prohibited. One of the reasons the censors gave for prohibition was that these books offered “unlimited fantasy.” To explore this idea, in one workshop the kids sang the song “The Backward Kingdom” (“El reino del revés”), by the well-known Argentine singer María Elena Walsh. After hearing the charming lyrics (birds swim, fish fly, babies have beards, 2 + 2 = 3, etc.), students brainstormed to generate their own inside-out or upside-down examples. One child mentioned raining up, another suggested that big kids nap while little kids play, and a third proposed cars driving on the sidewalk while kids play in the street. Upset by this disorder, one of the children exclaimed, “No, that's impossible!” until the boy who imagined cars on sidewalks explained, “But we're just imagining!” His classmate responded, “Oh, okay, in that case it's possible.”
Three Stories
Authors: Steward Frank R. , Gruesser John , Murphy Gretchen
Published: September 2011

Thwarted romances between Garrisoned American Soldiers and Young Filipinas, problems of translation in a multilingual contact zone, and the precarious masculine authority of the imperial agent irresistibly drawn to the mysterious women who surround him—these are the subjects of Frank R. Steward's short fiction about the American military occupation of the Philippines. But Steward's perspective as an African American military officer complicates efforts to interpret such familiar colonial scenarios. The stories' formal experimentation makes them a significant discovery in the archives of empire.
Choice of Summary Statistic Weights in Approximate Bayesian Computation
Authors: Jung Hsuan , Marjoram Paul
Published: September 2011

In this paper, we develop a Genetic Algorithm that can address the fundamental problem of how one should weight the summary statistics included in an approximate Bayesian computation analysis built around an accept/reject algorithm, and how one might choose the tolerance for that analysis. We then demonstrate that using weighted statistics, and a well-chosen tolerance, in such an approximate Bayesian computation approach can result in improved performance, when compared to unweighted analyses, using one example drawn purely from statistics and two drawn from the estimation of population genetics parameters.
Assessment of Electronic Health Record Usability with Undergraduate Nursing Students
Authors: Jones Stephanie , Donelle Lorie
Published: September 2011

Health information technology (HIT), and specifically electronic health records (EHR), are recognized as fundamental tools for collecting, storing, retrieving, and monitoring patient care and information. However, few schools of nursing have incorporated theoretical or practical aspects of HIT competencies within the educational curriculum. The purpose of this study was to conduct a usability assessment to explore undergraduate nursing student electronic health record documentation knowledge and skill, using a patient case scenario to inform the development of an informatics-based undergraduate nursing curriculum. Three themes were identified: “Being a Novice User/Practitioner,” “Confidentiality and Security,” and “Repetition and Practice.” Integration of the EHR into nursing curriculum will allow students an EHR apprenticeship with the potential to enhance understanding and skill of nursing processes, documentation, and critical thinking. Findings will also guide teaching and learning strategies that will respond to rising expectations for competency with health information technology.
Prospectively Determined Impact of Type 1 Diabetes on Brain Volume During Development
Authors: Perantie Dana C. , Koller Jonathan M. , Weaver Patrick M. , Lugar Heather M. , Black Kevin J. , White Neil H. , Hershey Tamara
Published: September 2011

OBJECTIVE

The impact of type 1 diabetes mellitus (T1DM) on the developing central nervous system is not well understood. Cross-sectional, retrospective studies suggest that exposure to glycemic extremes during development is harmful to brain structure in youth with T1DM. However, these studies cannot identify brain regions that change differentially over time depending on the degree of exposure to glycemic extremes.

RESEARCH DESIGN AND METHODS

We performed a longitudinal, prospective structural neuroimaging study of youth with T1DM (n = 75; mean age = 12.5 years) and their nondiabetic siblings (n = 25; mean age = 12.5 years). Each participant was scanned twice, separated by 2 years. Blood glucose control measurements (HbA1c, glucose meter results, and reports of severe hypoglycemia) were acquired during the 2-year follow-up. Sophisticated image registration algorithms were performed, followed by whole brain and voxel-wise statistical analyses of the change in gray and white matter volume, controlling for age, sex, and age of diabetes onset.

RESULTS

The T1DM and nondiabetic control (NDC) sibling groups did not differ in whole brain or voxel-wise change over the 2-year follow-up. However, within the T1DM group, participants with more hyperglycemia had a greater decrease in whole brain gray matter compared with those with less hyperglycemia (P < 0.05). Participants who experienced severe hypoglycemia had greater decreases in occipital/parietal white matter volume compared with those with no severe hypoglycemia (P < 0.05) and compared with the NDC sibling group (P < 0.05).

CONCLUSIONS

These results demonstrate that within diabetes, exposure to hyperglycemia and severe hypoglycemia may result in subtle deviation from normal developmental trajectories of the brain.
Depressive Symptoms, Antidepressant Medication Use, and Insulin Resistance
Authors: Pyykkönen Antti-Jussi , Räikkönen Katri , Tuomi Tiinamaija , Eriksson Johan G. , Groop Leif , Isomaa Bo
Published: September 2011

OBJECTIVE

Although insulin resistance (IR) may underlie associations between depressive symptoms and diabetes, previous findings have been contradictory. We examined whether depressive symptoms associate with IR and insulin secretion, and, additionally, whether antidepressant medication use may modulate such associations.

RESEARCH DESIGN AND METHODS

A total of 4,419 individuals underwent an oral glucose tolerance test (OGTT). Participants with previously or newly diagnosed diabetes are excluded from this sample. The homeostasis model assessment of IR (HOMA-IR) and corrected insulin response (CIR) were calculated. Depressive symptoms and antidepressant medication use were self-reported.

RESULTS

After controlling for confounding factors, depressive symptoms were associated with higher fasting and 30-min insulin during the OGTT and higher HOMA-IR but not CIR. Antidepressant medication use failed to modify these associations.

CONCLUSIONS

Depressive symptoms are associated with IR but not with changes in insulin response when corrected for IR in individuals without previously or newly diagnosed diabetes.
Baroreflex Sensitivity and Its Response to Deep Breathing Predict Increase in Blood Pressure in Type 1 Diabetes in a 5-Year Follow-Up
Authors: Rosengård-Bärlund Milla , Bernardi Luciano , Sandelin Anna , Forsblom Carol , Groop Per-Henrik ,   on behalf of the FinnDiane Study Group
Published: September 2011

OBJECTIVE

We have recently demonstrated that early autonomic dysfunction, defined as low baroreflex sensitivity (BRS), could be functional and reversible. However, potential temporal changes in BRS have not yet been addressed by longitudinal studies in type 1 diabetes. Moreover, it is not known whether low BRS predisposes to hypertension or other nonfatal diabetes complications.

RESEARCH DESIGN AND METHODS

We conducted a 5-year prospective study including 80 patients with type 1 diabetes. We measured ambulatory blood pressure and autonomic function tests. BRS was assessed by six different methods during spontaneous, controlled, and slow deep breathing at baseline and follow-up.

RESULTS

Spontaneous BRS declined over time (BRSaverage 16.2 ± 0.8 vs. 13.2 ± 0.8 ms/mmHg; P < 0.01), but the change was not significant when adjusted for time of follow-up. Low BRS at baseline did not progress to cardiac autonomic neuropathy but predicted an increase in the nighttime systolic blood pressure (BRSaverage r = −0.37; P < 0.05). Additionally, BRS response to deep breathing at baseline predicted an increase in 24-h ambulatory blood pressure (BRS-αLF r = 0.323–0.346; P < 0.05).

CONCLUSIONS

The decline in spontaneous BRS over time in patients with type 1 diabetes seems to be due to normal aging, which supports a functional etiology behind early autonomic derangements. Decreased resting BRS and the magnitude of improvement by deep breathing may be due to sympathovagal imbalance, a well-known mechanism in the development of hypertension. Early interventions aiming to reduce sympathetic overactivity in patients with low BRS might delay the development of hypertension.
Low Glycated Hemoglobin and Liver Disease in the U.S. Population
Authors: Christman Andrea L. , Lazo Mariana , Clark Jeanne M. , Selvin Elizabeth
Published: September 2011

OBJECTIVE

To characterize the association of low HbA1c values (<4.0%) with liver enzymes and steatosis.

RESEARCH DESIGN AND METHODS

Cross-sectional study of 12,533 participants without diabetes aged <20 years in the Third National Health and Nutrition Examination Survey (1988–1994). Logistic regression models were adjusted for demographic, lifestyle, and health status variables.

RESULTS

HbA1c values ranged from 3.2 to 15.7%, and 84 participants had HbA1c <4.0% in the population (mean age 44, 52% female, 15% black or Hispanic). We observed J-shaped associations between HbA1c and liver enzymes and hepatic steatosis. In adjusted models, HbA1c <4.0% was strongly associated with elevated alanine aminotransferase (OR 3.62 [95% CI 1.09–12.02]) and aspartate aminotransferase (6.80 [2.99–15.43]).

CONCLUSIONS

Low HbA1c values were associated with liver enzymes and steatosis in the U.S. population. Liver disease may partially explain the association of HbA1c with mortality and other long-term outcomes.
Inhibitor-2 induced M-phase arrest in Xenopus cycling egg extracts is dependent on MAPK activation
Authors: Khandani Arian , Mohtashami Mahmood , Camirand Anne
Published: September 2011

The evolutionarily-conserved protein phosphatase 1 (PP1) plays a central role in dephosphorylation of phosphoproteins during the M phase of the cell cycle. We demonstrate here that the PP1 inhibitor inhibitor-2 protein (Inh-2) induces an M-phase arrest in Xenopus cycling egg extracts. Interestingly, the characteristics of this M-phase arrest are similar to those of mitogen-activated protein kinase (p42MAPK)-induced M-phase arrest. This prompted us to investigate whether Inh-2-induced M-phase arrest was dependent on activation of the p42MAPK pathway. We demonstrate here that MAPK activity is required for Inh-2-induced M-phase arrest, as inhibition of MAPK by PD98059 allowed cycling extracts to exit M phase, despite the presence of Inh-2. We next investigated whether Inh-2 phosphorylation by the MAPK pathway was required to induce an M-phase arrest. We discovered that while p90Rsk (a MAPK protein required for M-phase arrest) is able to phosphorylate Inh-2, this phosphorylation is not required for Inh-2 function. Overall, our results suggest a novel mechanism linking p42MAPK and PP1 pathways during M phase of the cell cycle.
Infiltration of M2 Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma Correlates with Tumor Malignancy
Authors: Mori Kazumasa , Hiroi Miki , Shimada Jun , Ohmori Yoshihiro
Published: September 2011

Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment of many solid tumors. The functional competence of TAMs varies depending on the type of tumors and their respective microenvironments. The classically activated M1 macrophages exhibit antitumor functions, whereas the alternatively activated M2 macrophages exhibit protumor functions that contribute to tumor development and progression. Although TAMs have been detected in oral squamous cell carcinoma (OSCC), little is known about their phenotype. In the present study, we performed an immunohistochemical analysis to identify TAMs in surgically resected specimens from 50 patients with OSCC and evaluated the relationship between infiltrated TAMs and the pathological grade of OSCC. Positive staining for CD163, which has been used as a marker for M2 macrophages, was observed in OSCC specimens, and the percentages of CD163+ cells were significantly increased based on the pathological grade. CD163+ cells were detected in the tumor stroma in grade I tumors, whereas an increase in the CD163+ cells in the tumor nest was observed in higher grades of tumors. Although infiltrated CD4+ and CD8+ T cells were detected in all pathological grades of OSCC, no correlation between the infiltrated T cells and the CD163+ TAMs was observed. These results indicate that the infiltrated TAMs in OSCC have an M2 phenotype and that the M2 macrophages may participate in the development of OSCC.
Building Trust—One Gift at a Time
Authors: Servátka Maroš , Tucker Steven , Vadovič Radovan
Published: September 2011

This paper reports an experiment evaluating the effect of gift giving on building trust. We have nested our explorations in the standard version of the investment game. Our gift treatment includes a dictator stage in which the trustee decides whether to give a gift to the trustor before both of them proceed to play the investment game. We observe that in such case the majority of trustees offer their endowment to trustors. Consequently, receiving a gift significantly increases the amounts sent by trustors when controlling for the differences in payoffs created by it. Trustees are, however, not better off by giving a gift as the increase in the amount sent by trustors is not large enough to offset the trustees’ loss associated with the cost of giving a gift.
Overweight and Obesity and Associated Factors among School-Aged Adolescents in Ghana and Uganda
Authors: Peltzer Karl , Pengpid Supa
Published: September 2011

The aim of this study was to assess overweight and obesity and associated factors in school-going adolescents in low income African countries (Ghana, Uganda). The total sample included 5,613 school children aged 13 to 15 years from nationally representative samples from two African countries. Bivariate and multivariable analyses were conducted to assess the relationship between dietary behavior, substance use, physical activity, psychosocial factors and overweight or obesity. The prevalence of overweight and obesity was determined based on self-reported height and weight and the international child body mass index standards. Results indicate a prevalence of overweight or obesity of 10.4% among girls and 3.2% among boys, and 0.9% and 0.5% obesity only among girls and boys, respectively. Among girls smoking cigarettes and loneliness and among boys smoking cigarettes were found to be associated with overweight or obesity in multivariable analysis. Overweight status was not associated with the intake of fruits, vegetables, and sedentary behavior. Low prevalence rates of overweight or obesity were found in Ghana and Uganda. Smoking cessation and social programs could be integrated into strategies to prevent and treat overweight and obesity in youth.
Effect of 2-Hydroxypropyl-β-cyclodextrin on Solubility of Sparingly Soluble Drug Derivatives of Anthranilic Acid
Authors: Domańska Urszula , Pelczarska Aleksandra , Pobudkowska Aneta
Published: September 2011

Guest-host complex formation of three drug derivatives of anthranilic acid, mefenamic acid, niflumic acid, and flufenamic acid with 2-hydroxypropyl-β-cyclodextrin (2HP-β-CD) in aqueous solutions was investigated using “Phase solubility study” with UV-vis spectrophotometry. Solubility of sparingly soluble drugs has been improved by addition of 2HP-β-CD at two temperatures 298.15 K and 310.15 K and two pH values 2 and 7. The influence of different 2HP-β-CD concentration on solubility of drugs at different pH and temperatures has been investigated. The 2HP-β-CD-drug complex stability constants (Ks), and dissociations constants (Kd), as well as the thermodynamic parameters of reaction, i.e., the free energy change (ΔG), the enthalpy change (ΔH) and the entropy change (ΔS), were determined. The experimental data indicated formation of 1:1 inclusion complexes, which were found effective binders increasing the solubility of drugs.
Optimization of Antibacterial Activity of Perilla frutescens var. acuta Leaf against Staphylococcus aureus Using Evolutionary Operation Factorial Design Technique
Authors: Kim Dae-Hyun , Kim Young-Chan , Choi Ung-Kyu
Published: September 2011

This study was undertaken to optimize extraction using evolutionary operation-factorial (EVOP) design technique to elicit the antibacterial activity of Perilla frutescens var. acuta leaf against Staphylococcus aureus ATCC6538. Higher antibacterial activity was achieved at higher extraction temperature and over a longer extraction time. Antibacterial activity was not affected by differentiation of the ethanol concentration in the extraction solvent. The maximum antibacterial activity of ethanolic extract of P. frutescens leaf against S. aureus was obtained at 75 °C (R = −0.7904**) extraction temperature, 24 h (R = −0.7273**) extraction time, and 45% (R = −0.0635) ethanol concentration. The population of S. aureus was decreased from 7.535 log CFU/mL in the initial set to 4.865 log CFU/mL in the third set by EVOP factorial design technique, as well as to 2.600 log CFU/mL by extraction with ethyl acetate. Further, the ethyl acetate extract revealed the highest phenolic contents (111.3 ± 8.6 mg% of dry sample) as compared to the other extracts. Also, the scanning electronic microscopic study of the ethanolic extract of P. frutescens revealed potential detrimental effect on the morphology of S. aureus.
Genetic Variation of the Nile Soft-Shelled Turtle (Trionyx triunguis)
Authors: Güçlü Özgür , Ulger Celal , Türkozan Oğuz
Published: September 2011

We studied the genetic structure of Trionyx triunguis populations from the Mediterranean and African continent based on mtDNA D-loop (776 bp) and nine microsatellite loci. A total of 102 polymorphic sites and 13 mtDNA haplotypes were described. Nucleotide diversity and haplotypes diversity were 0.047 and 0.974 respectively. Both mtDNA and nDNA supported the existence of two main management units as the Mediterranean and Africa. Based on the mtDNA results, the Mediterranean can be divided into two subunits; western Turkey and the eastern Mediterranean.
A Determination of Potential α-Glucosidase Inhibitors from Azuki Beans (Vigna angularis)
Authors: Yao Yang , Cheng Xuzhen , Wang Lixia , Wang Suhua , Ren Guixing
Published: September 2011

A 70% ethanol extract from azuki beans (Vigna angularis) was extracted further with CH2Cl2, EtOAc and n-BuOH to afford four fractions: CH2Cl2-soluble, EtOAc-soluble, n-BuOH-soluble and residual extract fractions. The EtOAc-soluble fractions showed the highest α-glucosidase inhibitory activity. Two pure flavonoid compounds, vitexin and isovitexin, were isolated (using the enzyme assay-guide fractionation method) from the EtOAc-soluble fractions. We further evaluated the interaction between the flavonoid compounds and α-glucosidase by fluorescence spectroscopy. Vitexin and isovitexin showed high inhibitory activities, with IC50 values of 0.4 mg·mL−1 and 4.8 mg·mL−1, respectively. This is the first study of the active compositions of azuki beans against α-glucosidase.
Metabolomics of Oxidative Stress in Recent Studies of Endogenous and Exogenously Administered Intermediate Metabolites
Authors: Liu Jia , Litt Lawrence , Segal Mark R. , Kelly Mark J. S. , Pelton Jeffrey G. , Kim Myungwon
Published: September 2011

Aerobic metabolism occurs in a background of oxygen radicals and reactive oxygen species (ROS) that originate from the incomplete reduction of molecular oxygen in electron transfer reactions. The essential role of aerobic metabolism, the generation and consumption of ATP and other high energy phosphates, sustains a balance of approximately 3000 essential human metabolites that serve not only as nutrients, but also as antioxidants, neurotransmitters, osmolytes, and participants in ligand-based and other cellular signaling. In hypoxia, ischemia, and oxidative stress, where pathological circumstances cause oxygen radicals to form at a rate greater than is possible for their consumption, changes in the composition of metabolite ensembles, or metabolomes, can be associated with physiological changes. Metabolomics and metabonomics are a scientific disciplines that focuse on quantifying dynamic metabolome responses, using multivariate analytical approaches derived from methods within genomics, a discipline that consolidated innovative analysis techniques for situations where the number of biomarkers (metabolites in our case) greatly exceeds the number of subjects. This review focuses on the behavior of cytosolic, mitochondrial, and redox metabolites in ameliorating or exacerbating oxidative stress. After reviewing work regarding a small number of metabolites—pyruvate, ethyl pyruvate, and fructose-1,6-bisphosphate—whose exogenous administration was found to ameliorate oxidative stress, a subsequent section reviews basic multivariate statistical methods common in metabolomics research, and their application in human and preclinical studies emphasizing oxidative stress. Particular attention is paid to new NMR spectroscopy methods in metabolomics and metabonomics. Because complex relationships connect oxidative stress to so many physiological processes, studies from different disciplines were reviewed. All, however, shared the common goal of ultimately developing “omics”-based, diagnostic tests to help influence therapies.
Myosin Assembly, Maintenance and Degradation in Muscle: Role of the Chaperone UNC-45 in Myosin Thick Filament Dynamics
Authors: Kachur Torah  M. , Pilgrim David  B.
Published: September 2011

Myofibrillogenesis in striated muscle cells requires a precise ordered pathway to assemble different proteins into a linear array of sarcomeres. The sarcomere relies on interdigitated thick and thin filaments to ensure muscle contraction, as well as properly folded and catalytically active myosin head. Achieving this organization requires a series of protein folding and assembly steps. The folding of the myosin head domain requires chaperone activity to attain its functional conformation. Folded or unfolded myosin can spontaneously assemble into short myosin filaments, but further assembly requires the short and incomplete myosin filaments to assemble into the developing thick filament. These longer filaments are then incorporated into the developing sarcomere of the muscle. Both myosin folding and assembly require factors to coordinate the formation of the thick filament in the sarcomere and these factors include chaperone molecules. Myosin folding and sarcomeric assembly requires association of classical chaperones as well as folding cofactors such as UNC-45. Recent research has suggested that UNC-45 is required beyond initial myosin head folding and may be directly or indirectly involved in different stages of myosin thick filament assembly, maintenance and degradation.
Design of Energy Aware Adder Circuits Considering Random Intra-Die Process Variations
Authors: Lanuzza Marco , Frustaci Fabio , Perri Stefania , Corsonello Pasquale
Published: September 2011

Energy consumption is one of the main barriers to current high-performance designs. Moreover, the increased variability experienced in advanced process technologies implies further timing yield concerns and therefore intensifies this obstacle. Thus, proper techniques to achieve robust designs are a critical requirement for integrated circuit success. In this paper, the influence of intra-die random process variations is analyzed considering the particular case of the design of energy aware adder circuits. Five well known adder circuits were designed exploiting an industrial 45 nm static complementary metal-oxide semiconductor (CMOS) standard cell library. The designed adders were comparatively evaluated under different energy constraints. As a main result, the performed analysis demonstrates that, for a given energy budget, simpler circuits (which are conventionally identified as low-energy slow architectures) operating at higher power supply voltages can achieve a timing yield significantly better than more complex faster adders when used in low-power design with supply voltages lower than nominal.
Enhancing Crystallinity and Orientation by Hot-Stretching to Improve the Mechanical Properties of Electrospun Partially Aligned Polyacrylonitrile (PAN) Nanocomposites
Authors: Song Zhenyu , Hou Xiaoxiao , Zhang Liqun , Wu Sizhu
Published: September 2011

Partially aligned polyacrylonitrile (PAN)-based nanofibers were electrospun from PAN and PAN/single-walled carbon nanotubes (SWNTs) in a solution of dimethylformamide (DMF) to make the nanofiber composites. The as-spun nanofibers were then hot-stretched in the oven to enhance its orientation and crystallinity. With the introduction of SWNTs and by the hot-stretched process, the mechanical properties will be enhanced correspondingly. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray scattering (XRD), differential scanning calorimetry (DSC), and the tensile test were used to characterize the microstructure and performances of the nanofibers. The orientation and crystallinity of the as-spun and hot-stretched nanofibers confirmed by X-ray have increased. Differential scanning calorimetry showed that the glass transition temperature of PAN increased about 3 °C by an addition of 0.75 wt% SWNTs indicating a strong interfacial interaction between PAN and SWNTs. The tensile strength and the modulus of the nanofibers increased revealing significant load transfer across the nanotube-matrix interface. For PAN nanofibers, the improved fiber alignment, orientation and crystallinity resulted in enhanced mechanical properties, such as the tensile strength and modulus of the nanofibers. It was concluded that the hot-stretched nanofiber and the PAN/SWNTs nanofibers can be used as a potential precursor to produce high-performance nanocomposites.
Magnetoelectric Interactions in Lead-Based and Lead-Free Composites
Authors: Bichurin Mirza , Petrov Vladimir , Zakharov Anatoly , Kovalenko Denis , Yang Su Chul , Maurya Deepam , Bedekar Vishwas , Priya Shashank
Published: September 2011

Magnetoelectric (ME) composites that simultaneously exhibit ferroelectricity and ferromagnetism have recently gained significant attention as evident by the increasing number of publications. These research activities are direct results of the fact that multiferroic magnetoelectrics offer significant technological promise for multiple devices. Appropriate choice of phases with co-firing capability, magnetostriction and piezoelectric coefficient, such as Ni-PZT and NZFO-PZT, has resulted in fabrication of prototype components that promise transition. In this manuscript, we report the properties of Ni-PZT and NZFO-PZT composites in terms of ME voltage coefficients as a function of frequency and magnetic DC bias. In order to overcome the problem of toxicity of lead, we have conducted experiments with Pb-free piezoelectric compositions. Results are presented on the magnetoelectric performance of Ni-NKN, Ni-NBTBT and NZFO-NKN, NZFO-NBTBT systems illustrating their importance as an environmentally friendly alternative.
Phylogenetic Identification of Fungi Isolated from the Marine Sponge Tethya aurantium and Identification of Their Secondary Metabolites
Authors: Wiese Jutta , Ohlendorf Birgit , Blümel Martina , Schmaljohann Rolf , Imhoff Johannes F.
Published: September 2011

Fungi associated with the marine sponge Tethya aurantium were isolated and identified by morphological criteria and phylogenetic analyses based on internal transcribed spacer (ITS) regions. They were evaluated with regard to their secondary metabolite profiles. Among the 81 isolates which were characterized, members of 21 genera were identified. Some genera like Acremonium, Aspergillus, Fusarium, Penicillium, Phoma, and Trichoderma are quite common, but we also isolated strains belonging to genera like Botryosphaeria, Epicoccum, Parasphaeosphaeria, and Tritirachium which have rarely been reported from sponges. Members affiliated to the genera Bartalinia and Volutella as well as to a presumably new Phoma species were first isolated from a sponge in this study. On the basis of their classification, strains were selected for analysis of their ability to produce natural products. In addition to a number of known compounds, several new natural products were identified. The scopularides and sorbifuranones have been described elsewhere. We have isolated four additional substances which have not been described so far. The new metabolite cillifuranone (1) was isolated from Penicillium chrysogenum strain LF066. The structure of cillifuranone (1) was elucidated based on 1D and 2D NMR analysis and turned out to be a previously postulated intermediate in sorbifuranone biosynthesis. Only minor antibiotic bioactivities of this compound were found so far.
Design of New α-Conotoxins: From Computer Modeling to Synthesis of Potent Cholinergic Compounds
Authors: Kasheverov Igor E. , Zhmak Maxim N. , Khruschov Alexey Y. , Tsetlin Victor I.
Published: September 2011

A series of 14 new analogs of α-conotoxin PnIA Conus pennaceus was synthesized and tested for binding to the human α7 nicotinic acetylcholine receptor (nAChR) and acetylcholine-binding proteins (AChBP) Lymnaea stagnalis and Aplysia californica. Based on computer modeling and the X-ray structure of the A. californica AChBP complex with the PnIA[A10L, D14K] analog [1], single and multiple amino acid substitutions were introduced in α-conotoxin PnIA aimed at compounds of higher affinity and selectivity. Three analogs, PnIA[L5H], PnIA[A10L, D14K] and PnIA[L5R, A10L, D14R], have high affinities for AChBPs or α7 nAChR, as found in competition with radioiodinated α-bungarotoxin. That is why we prepared radioiodinated derivatives of these α-conotoxins, demonstrated their specific binding and found that among the tested synthetic analogs, most had almost 10-fold higher affinity in competition with radioactive α-conotoxins as compared to competition with radioactive α-bungarotoxin. Thus, radioiodinated α-conotoxins are a more sensitive tool for checking the activity of novel α-conotoxins and other compounds quickly dissociating from the receptor complexes.
High-Performance Liquid Chromatographic Quantification of Flavonoids in Eriocaulaceae Species and Their Antimicrobial Activity
Authors: Da Silva Marcelo Aparecido , Cardoso Claudia Andréa Lima , Vilegas Wagner , Dos Santos Lourdes Campaner
Published: September 2011

Quantification of prepared samples by analysis using high performance liquid chromatography with DAD detection was developed to analyze rutin, 6-methoxyapigenin, and 6-methoxyapigenin-7-O-β-D-glucopyranoside isolated from methanolic extracts of different genus: Syngonanthus, Leiothix and Eriocaulon (Eriocaulaceae). The linearity, accuracy, and the inter-day precision of the procedure were evaluated. The calibration curves were linear. The recoveries of the flavonoids in the samples analyzed were 96.3% to 98.5%. The percentage coefficient of variation for the quantitative analysis of the flavonoids in the analyses of the samples was under 5%. The antimicrobial activity of the five methanol extracts of these Eriocaulaceae species was assayed against the microorganisms Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Salmonella setubal, Saccharomyces cerevisiae and Candida albicans. Measured MIC values ranged from 1.25 to 10.00 mg/mL. The flavonoid contents suggest that Eriocaulaceae species may be a promising source of compounds to produce natural phytomedicines.
Efficient In Vivo Selection of a Novel Tumor-Associated Peptide from a Phage Display Library
Authors: Veleva Anka N. , Nepal Desh B. , Frederick C. Brandon , Schwab Jacob , Lockyer Pamela , Yuan Hong , Lalush David S. , Patterson Cam
Published: September 2011

We developed a screening procedure to identify ligands from a phage display random peptide library that are selective for circulating bone marrow derived cells homing to angiogenic tumors. Panning the library on blood outgrowth endothelial cell suspension in vitro followed by in vivo selection based on homing of bone marrow-bound phage to angiogenic tumors, yielded the peptide QFPPKLTNNSML. Upon intravenous injection phage displaying this peptide homed to Lewis lung carcinoma (LLC) tumors in vivo whereas control phage did not localize to tumor tissue. Phage carrying the QFPPKLTNNSML peptide labeled with 64Cu radionuclide when administered intravenously into a tumor bearing mouse was detected noninvasively with positron emission tomography (PET) around the tumor. These proof-of-principle experiments demonstrate the ability of the QFPPKLTNNSML peptide to deliver payload (radiolabeled phage conjugates) in vivo to sites of ongoing angiogenesis and point to its potential clinical utility in a variety of physiologic and pathologic processes where neovascular growth is a critical component.
DNA-Templated Preparation of Gold Nanoparticles
Authors: Sohn Jeong Sun , Kwon Young Wan , Jin Jung Il , Jo Byung Wook
Published: September 2011

DNA-mediated gold nanoparticles were prepared by chemical reduction of DNA-Au(III) complex. The DNA-Au(III) was first formed by reacting DNA with HAuCl4 at a pH of 5.6. The complex in solution was reacted with hydrazine reducing Au(III) to Au. The reduced Au formed nanodimensional aggregates. The particle distributions were obtained by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). This method resulted in a rather uniform dispersion of Au nanoparticles of near-spherical shape and 45~80 nm in diameter. Gold nanoparticles were embedded and stabilized by DNA.