bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutrition and oxidative drug metabolism in man: Relative influence of dietary lipids, carbohydrate, and protein
Authors: Anderson Karl E. , Conney Allan H. , Kappas Attallah
Published: January 2016

Effects of an increase in dietary lipid content relative to protein or carbohydrate, and consequences of an alteration in dietary fatty acid composition on oxidative metabolism of drugs in man were examined. Two studies were carried out in healthy subjects fed carefully controlled solid food diets. In the first, the isocaloric substitution of fat for carbohydrate produced little or no statistically significant change in the mean plasma half‐lifes (t½s), apparent volumes of distribution (aVD), or metabolic clearance rates (MCR) of antipyrine (t½, 12.3 ± 0.5 hr and 11.7 ± 0.6 hr on the high carbohydrate and high fat diets, respectively) or theophylline (t½, 7.9 ± 0.4 hr on both diets) after periods of 10 to 14 days on each diet; but when intake was changed to a high protein diet metabolism rates for both drugs were greater than on either the high fat or the high carbohydrate diet in that mean plasma antipyrine t½ decreased to 9.9 ± 0.5 hr and theophylline t½ to 5.8 ± 0.3 hr, with increases in MCR for both drugs. In the second study, which was carried out with 9 subjects on high fat and high carbohydrate diets, the isocaloric substitution of either saturated fat (butter) or polyunsaturated fat (corn oil) for carbohydrate (without changing total protein content) produced no significant changes in rates of metabolism of these drugs, whereas the alterations in dietary fatty acid composition produced expected changes in plasma concentrations of cholesterol and triglycerides. Our observations suggest that protein, when substituted for either dietary carbohydrate or lipid, has a clear inducing influence on oxidative drug metabolism in man, and the degree of fatty acid unsaturation has little or no effect on rates of metabolism of these drugs despite marked changes in plasma lipids.
How much is enough?
Authors: Sicé Jean
Published: January 2016

A distinguished clinician, when recently asked to elaborate on this quotation, offered some provocative comments. First, he said, this statement either has not received the attention that it deserves, or those who recognize its importance do not know what to do about it. Second, he added, improper dosages have probably become a far greater cause of error in therapy than is the prescription of inappropriate drugs. But in all fairness, he concluded, let us not forget that determining the dose required by a particular patient is more difficult than selecting the drug indicated in the treatment of his illness. After all, he remarked, we now have several authoritative compendia that list the drug or drugs known to be the most effective against all types of diseases. But few of these texts go beyond recommending ranges of doses which often are so wide that one does not know where to start and where to stop.
Naphthoxylactic acid after single and long‐term doses of propranolol
Authors: Walle Thomas , Conradi Edward C. , Walle U. Kristina , Fagan Timothy C. , Gaffney Thomas E.
Published: January 2016

The disposition of naphthoxylactic acid (NLA) and propranolol was determined after single intravenous and oral doses of propranolol in 5 subjects and during long‐term therapy in 8 hypertensive patients. The area under the plasma concentration/time curve (AUC) of NLA exceeded that of propranolol twofold after an intravenous 4‐mg dose of propranolol but tenfold after single oral 20‐mg and 80‐mg doses, indicating a high degree of presystemic formation of NLA. The time to peak concentration (1.5 to 2 hr) and the plasma half‐life of NLA (3.1 to 4.2 hr) were in the same range as for propranolol. A two‐ to threefold accumulation of NLA in plasma was indicated after chronic propranolol therapy. Whereas plasma concentrations and urinary excretion of NLA increased linearly with dose on long‐term propranolol dosage, there was a nonlinear relationship between propranolol plasma levels and dose. This resulted in a markedly reduced NLA/propranolol plasma level ratio with increasing doses (from 10 to 28 at a daily 80‐mg propranolol dose to about 3 at a daily 960‐mg dose). The urinary excretion of NLA accounted for about 14% of the propranolol dose over the dose range studied. The finding that the renal clearance of NLA (18 to 54 ml/min) and plasma levels were dependent on glomerular filtration rate (GFR) indicates that renal elimination is the main determinant of total body clearance of NLA and that it may accumulate strikingly in patients with severe renal disease.
Cefamandole kinetics in uremic patients undergoing hemodialysis
Authors: Gambertoglio John G. , Aziz Nik S. , Lin Emil T. , Grausz Henry , Naughton James L. , Benet Leslie Z.
Published: January 2016

A single intravenous 15 mg/kg dose of cefamandole was given to 6 patients in chronic renal failure before hemodialysis, and 3 were examined during an interdialysis period. Mean cefamandole clearance by hemodialysis was 24 ± 12 ml/min; 35 ± 15% of the dose was recovered in the dialysate. The cefamandole half‐life (t½) on dialysis was 4.0 ± 0.29 hr; off dialysis it was 13.9 ±4.2 hr. High urine concentrations of cefamandole in these patients suggests usefulness in urinary tract infections.
Plasma levels of chlorimipramine and its demethyl metabolite during treatment of depression
Authors: Träskman Lil , Åsberg Marie , Bertiisson Leif , Cronholm Börje , Mellström Britt , Neckers Leonard M. , Sjöqvist Folke , Thorén Peter , Tybring Gunnel
Published: January 2016

The biochemical and antidepressant effects of chlorimipramine (Cl) were studied in depressed patients after 3 wk of treatment. In vitro studies performed with rat brain slices incubated in human plasma showed that chlorimipramine and its demethyl metabolite (DMCI) are fairly specific blockers of serotonin and norepinephrine uptake. The uptake inhibition of serotonin and norepinephrine in plasma drawn from patients during treatment correlated with the plasma levels of parent drug and metabolite. Treatment with Cl caused a decrease of the main serotonin (5‐HIAA) and norepinephrine metabolites (HMPG) but had no significant mean effect on the major dopamine metabolite (HVA) or on tryptophan in cerebrospinal fluid (CSF). The 5‐HIAA decrease in CSF correlated with the plasma concentration of Cl within the range 80 to 360 nmole/l. The HMPG decrease in CSF correlated with plasma DMCI concentration. The patients were subdivided into two groups, those with “low” and those with “high” CSF 5‐HIAA. In patients with a “high” pretreatment CSF 5‐HIAA, there was a positive correlation between amelioration of depression and plasma level of DMCI. In this patient group there also was a correlation between HMPG alteration and amelioration of depression. This finding supports the hypothesis that patients with “high” CSF 5‐HIAA levels benefit from treatment with norepinephrine uptake blockers. In the patient group with “low” CSF 5‐HIAA, correlations between plasma levels of Cl and DMCI and amelioration were consistently negative, albeit not significant, supporting the idea that these patients are a biochemical subgroup within the depressive illness with a different reaction to antidepressant drugs than those with “high” CSF 5‐HIAA levels.
Sulfinpyrazone kinetics after intravenous and oral administration
Authors: Lecaillon Jean B. , Souppart Claire , Schoeller Jean-Paul , Humbert Guy , Massias Pierre
Published: January 2016

Sulfinpyrazone kinetics has been investigated after intravenous and oral doses. They may be described by a 3‐compartment open model. In the body about half the drug is in the plasma or in interstitial fluids, which are readily equilibrated with plasma. Most of the rest is in an extravascular compartment, from which it easily diffuses back to the plasma. About 3% of the dose is still in the body after 24 hr and is located mainly in a deep compartment. After oral administration, sulfinpyrazone is quickly absorbed, largely from the stomach.
Effects of allopurinol on theophylline metabolism and clearance
Authors: Grygiel John J. , Wing Lindon M. H. , Farkas Julie , Birkett Donald J.
Published: January 2016

The effects of allopurinol on the plasma clearance and metabolism of theophylline in man were investigated under single‐dose and multiple‐dosing conditions. No change in theophylline clearance was found with the concomitant use of allopurinol but 1‐methylxanthine (1MX), a theophylline metabolite not previously described in man, was detected in urine during control and allopurinol treatment phases under both single‐ and multiple‐dosing conditions. 1MX excretion increased at the expense of 1‐methyluric acid (IMU) during the allopurinol treatment phase. It is proposed that the secondary biotransformation of 1MX to IMU is mediated by xanthine oxidase.
Acyclovir kinetics after intravenous infusion
Authors: de Miranda P. , Whitley R. J. , Blum M. R. , Keeney R. E. , Barton N. , Cocchetto D. M. , Good S. , Hemstreet G. P. , Kirk L. E. , Page D. A. , Elion G. B.
Published: January 2016

The disposition and safety of the antiviral drug acyclovir were studied in 14 subjects with advanced malignancies. Acyclovir was administered by a 1‐hr intravenous infusion at doses of 0.5, 1.0, 2.5, and 5.0 mg/kg. At the end of infusion, mean peak plasma levels (±SEM), determined by radioimmunoassay, were 6.4 ±0.7, 12.1 ±2.3, 14.9 ±2.7, and 33.7 ±7.1 µM. The plasma concentration‐time profiles could be described by a biexponential equation. The half‐life of acyclovir in the slow disposition phase ranged from 2.2 to 5 hr and the drug was detected in the plasma for at least 18 hr after infusion. The total body clearance ranged from 117 to 396 ml/min/1.73 m2. A proportionality between area under the curve and dose suggests that acyclovir exhibits dose‐independent kinetics in the dose range studied. There was wide variation in cumulative urinary excretion of unchanged drug, ranging from 30 to 69% of the dose. From renal clearances of acyclovir, which were higher than creatinine clearances, it appears that both glomerular filtration and tubular secretion contribute to its renal excretion. Analysis of the urine by reverse‐phase high‐performance liquid chromatography revealed the presence of the metabolite 9‐carboxymethoxymethylguanine. There was no indication of toxicity either clinically or from laboratory findings in any of the study subjects. This study demonstrates that in addition to selectivity and low toxicity, the kinetic profile and metabolic disposition of acyclovir make it an attractive candidate for therapy in a variety of herpes infections.
Changes in calcium excretion after prolonged metolazone therapy in recurrent stone formers
Authors: Lespier-Dexter Laura E. , Martinez-Maldonado Manuel
Published: January 2016

The handling of an acute oral calcium load in 22 men with recurrent calcium stone disease was studied before and after diuretic therapy. As a group, the patients had marginal hypercalciuria (150 mg calcium per gram of creatinine in a 24‐hr urine collection). Metolazone, a diuretic with an action in the cortical thick ascending limb of Henle's loop, was given in oral daily doses of 5.0 mg for periods of 9 to 34 mo. An oral calcium load induced a rapid rise in urine calcium excretion, which was blunted markedly by metolazone. Further analysis of the subjects revealed that one group (11 subjects) had higher baseline 24‐hr calcium excretion levels and higher parathyroid hormone (PTH) than the others. The effect of metolazone in reducing the calciuric response was significant only in this group. Thus, while long‐term treatment with metolazone inhibited the rise in urinary calcium excretion elicited by an oral calcium load, the effect was significant only in patients who had high baseline urinary calcium and PTH values. The reduction in calcium excretion in response to an acute calcium challenge may explain in part the beneficial effects of cortical diluting segment diuretics in recurrent stone formers.
Drebrin coordinates the actin and microtubule cytoskeleton during the initiation of axon collateral branches
Authors: Ketschek Andrea , Spillane Mirela , Dun Xin‐Peng , Hardy Holly , Chilton John , Gallo Gianluca
Published: January 2016

Drebrin is a cytoskeleton‐associated protein which can interact with both actin filaments and the tips of microtubules. Its roles have been studied mostly in dendrites, and the functions of drebrin in axons are less well understood. In this study, we analyzed the role of drebrin, through shRNA‐mediated depletion and overexpression, in the collateral branching of chicken embryonic sensory axons. We report that drebrin promotes the formation of axonal filopodia and collateral branches in vivo and in vitro. Live imaging of cytoskeletal dynamics revealed that drebrin promotes the formation of filopodia from precursor structures termed axonal actin patches. Endogenous drebrin localizes to actin patches and depletion studies indicate that drebrin contributes to the development of patches. In filopodia, endogenous drebrin localizes to the proximal portion of the filopodium. Drebrin was found to promote the stability of axonal filopodia and the entry of microtubule plus tips into axonal filopodia. The effects of drebrin on the stabilization of filopodia are independent of its effects on promoting microtubule targeting to filopodia. Inhibition of myosin II induces a redistribution of endogenous drebrin distally into filopodia, and further increases branching in drebrin overexpressing neurons. Finally, a 30 min treatment with the branch‐inducing signal nerve growth factor increases the levels of axonal drebrin. This study determines the specific roles of drebrin in the regulation of the axonal cytoskeleton, and provides evidence that drebrin contributes to the coordination of the actin and microtubule cytoskeleton during the initial stages of axon branching. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1092–1110, 2016
Glacier–groundwater stress gradients control alpine river biodiversity
Authors: Khamis Kieran , Brown Lee E. , Hannah David M. , Milner Alexander M.
Published: January 2016

In alpine river networks, water source (i.e. snow, ice or groundwater) plays a major role in influencing flow regimes, benthic habitat and macro‐invertebrate community structure. Across these systems, a natural stress gradient can be conceptualized, from rivers fed exclusively by meltwater (harsh habitat) to those with no melt input (relatively benign, groundwater fed). However, despite the current context of rapid glacier retreat, our understanding of linkages between meltwater contributions, physico‐chemical habitat and biodiversity remains limited. To address this research gap, habitat characteristics and macro‐invertebrate community structure were studied at 26 sites (five river basins) in the French Pyrénées across a meltwater gradient from 0% to 99%. A combination of generalized regression models and multivariate analyses showed that the stress gradient was associated with the following: (i) linear responses of key physico‐chemical habitat variables, in particular bed stability, (ii) unimodal responses at the community level (e.g. richness and total density peaks at 40–60% meltwater contribution), and (iii) both unimodal and monotonic responses at the level of individual taxa. Sites characterized by high contributions of meltwater, although species poor, were important for beta diversity because of their specialist endemic fauna. Our findings suggest that continued glacier and snowpack retreat due to expected future climate change are likely to lead to more homogeneous alpine river habitats (i.e. reduced meltwater–groundwater stress gradient breadth). As a result, increased alpha diversity is expected as previously harsh habitats become more favourable; however, an associated decrease in beta diversity is likely as glacial stream specialists become replaced by generalists. Copyright © 2016 John Wiley & Sons, Ltd.
Cryogenic Nanothermometer Based on the MIL‐103(Tb,Eu) Metal–Organic Framework
Authors: Ananias Duarte , Brites Carlos D. S. , Carlos Luís D. , Rocha João
Published: January 2016

The microporous metal–organic framework MIL‐103 doped with Tb3+ and Eu3+, formulated as [(Tb0.95Eu0.05)(btb)(H2O)]·(solv)x [H3btb = 1,3,5‐tris(4‐carboxyphenyl)benzene; solv = H2O, CH3OH] has been shown to be a good platform for luminescent ratiometric thermometry. Although operative over a wide range of temperatures (10–320 K), this material exhibits, in the cryogenic range (<100 K), one of the best performances of metal–organic frameworks, with a relative thermal sensitivity of 2.85 % K–1 at 14 K. The material exists in the form of nanoparticles, suitable for nanothermometry applications (e.g., microfluidics). Moreover, as MIL‐103 is nanoporous, its use as a multisensing platform deserves further consideration in the near future.
Hydrophilic Ethylene‐Glycol‐Based Ruthenium Sensitizers for Aqueous Dye‐Sensitized Solar Cells
Authors: Cisneros Robin , Beley Marc , Lapicque François , Gros Philippe C.
Published: January 2016

Invited for the cover of this issue is the group of Philippe C. Gros from Université de Lorraine, Nancy, France. The cover image shows the application of new hydrophilic ruthenium complexes as sensitizers in water‐based dye‐sensitized solar cells (DSSCs).
Handedness Preferences of Heterochiral Helical Peptides Containing Homochiral Peptide Segments
Authors: Demizu Yosuke , Yamashita Hiroko , Misawa Takashi , Doi Mitsunobu , Oba Makoto , Tanaka Masakazu , Kurihara Masaaki
Published: January 2016

A homochiral L‐Leu‐L‐Leu‐Aib segment was incorporated into the N‐ or C‐termini of left‐handed (M) helical peptides (D‐Leu‐L‐Leu‐Aib)n. We then investigated the preferred conformations of two sets of three peptides; i.e., Boc‐L‐Leu‐L‐Leu‐Aib‐(D‐Leu‐L‐Leu‐Aib)n‐OMe (n = 1: 1; 2: 2; 3: 3) and Boc‐(D‐Leu‐L‐Leu‐Aib)n‐L‐Leu‐L‐Leu‐Aib‐OMe (n = 1: 4; 2: 5; 3: 6), in solution and in the crystalline state. Nonapeptide 2 and dodecapeptide 3, each containing an N‐terminal L‐Leu‐L‐Leu‐Aib segment, formed left‐handed (M) helices as the preferred secondary structures in solution. In the crystalline state, nonapeptide 2 folded into an (M) α‐helical structure. Peptides 4–6, each containing a C‐terminal L‐Leu‐L‐Leu‐Aib segment, formed roughly equivalent amounts of right‐handed (P) and (M) helices.
Potentiometric Sensing of Aspirin Metabolite in Human Plasma and Pharmaceutical Preparations Using Co(III)‐complex Based Electrodes: Experimental and Quantum Chemical Calculations
Authors: Shehab Ola R. , Mansour Ahmed M.
Published: January 2016

Three novel poly vinyl chloride (PVC) (A), carbon paste (CP) (B), and coated glassy carbon‐MWCNT (CGC) (C) salicylate (sal−) sensors based on new synthesized [Co(L2Cl)Cl3(H2O)] ⋅ H2O complex (L2Cl=(1H‐benzimidazol‐2‐ylmethyl)‐N‐(2‐chloro‐phenyl)‐ amine)), o‐nitrophenyloctyl ether as a mediator and tridodecylmethylammonium chloride as a cationic additive were successfully used for determination of sal− in human plasma and pharmaceutical formulations. The sal−‐sensors exhibited enhanced sensitivity with slope of −63.5, −60.5 and −58.9 mV/decade and detection limit of 1.0×10−5, 4.0×10−7, and 1.0×10−6 mol L−1 for A–C sensors respectively. Quantum chemical calculations were carried out by HF and DFT/B3LYP methods to explore and investigate the interaction between the receptor and the different anions. The intermolecular H‐bond created between the uncoordinated CO of salicylate group and the secondary amino group in the complex is the key factor of the selectivity of the proposed sensor. A linear relation is established between the natural charge on the Co center and the value of the binding energy, where the decrease in positive charge is associated by an increase in the anion binding energy.
Association between depression and neuropathy in people with type 2 diabetes: a meta‐analysis
Authors: Bartoli Francesco , Carrà Giuseppe , Crocamo Cristina , Carretta Daniele , La Tegola Davide , Tabacchi Tommaso , Gamba Pierluigi , Clerici Massimo
Published: January 2016

Objective

Depression and neuropathy are frequent complications of type 2 diabetes. The current meta‐analysis aimed to estimate the association between depression and neuropathy in subjects with type 2 diabetes.

Methods

We systematically searched electronic databases for articles published up to February 2015, providing data on the association between depression and neuropathy in individuals with type 2 diabetes. No language restrictions were applied. The meta‐analysis generated random‐effect odds ratios with 95% confidence intervals (95% CI). Risk of publication bias and heterogeneity were estimated using the Egger test and I2 index, respectively. Leave‐one‐out analysis was performed. Data were analysed using stata.

Results

Thirteen studies were included in the meta‐analysis. Data on the association between depression and neuropathy were available for 3898 individuals with type 2 diabetes. Pooled analysis showed an association between depression and neuropathy, with an odds ratio of 2.01 (95% CI: 1.60–2.54; p < 0.001). There was no risk of publication bias (p = 0.064), and heterogeneity was moderate (I2 = 44.5%). Leave‐one‐out analysis confirmed consistency of the findings. The association appeared partly influenced by age, because studies selecting older people (sample mean age > 65 years) showed a slightly higher estimate for the association.

Conclusions

We found an association between depression and neuropathy among people with type 2 diabetes. Because of the cross‐sectional nature of included studies, the relationship between these two conditions might be bidirectional. Further research exploring factors that might moderate or mediate this association is needed. Targeted interventions for comorbid depression and neuropathy should be implemented in clinical practice. Copyright © 2016 John Wiley & Sons, Ltd.
Visual and Digital Texts
Authors: Botzakis Stergios
Published: January 2016

This column highlights and evaluates apps and websites to assist teachers, students, and other interested parties for learning about DNA, genes, heredity, and genetic disorders.
Professional Resources
Authors: Haddix Marcelle M.
Published: January 2016

Review of Other People's English: Code‐meshing, code‐switching, and African American literacy
Computational Participation
Authors: Burke Quinn , O'Byrne W. Ian , Kafai Yasmin B.
Published: January 2016

Understanding the computational concepts on which countless digital applications run offers learners the opportunity to no longer simply read such media but also become more discerning end users and potentially innovative “writers” of new media themselves. To think computationally—to solve problems, to design systems, and to process and organize information drawing on concepts fundamental to computer science—is seen as a crucial problem‐solving skill in the new millennium. It is not a matter of turning all adolescents into computer scientists but rather leveraging coding as a means to get youths more engaged in the workings of the Web‐based media that surround them.
A G-protein Subunit-α11 Loss-of-Function Mutation, Thr54Met, Causes Familial Hypocalciuric Hypercalcemia Type 2 (FHH2)
Authors: Gorvin Caroline M , Cranston Treena , Hannan Fadil M , Rust Nigel , Qureshi Asjid , Nesbit M Andrew , Thakker Rajesh V
Published: January 2016

Familial hypocalciuric hypercalcemia (FHH) is a genetically heterogeneous disorder with three variants, FHH1 to FHH3. FHH1 is caused by loss-of-function mutations of the calcium-sensing receptor (CaSR), a G-protein coupled receptor that predominantly signals via G-protein subunit alpha-11 (Gα11) to regulate calcium homeostasis. FHH2 is the result of loss-of-function mutations in Gα11, encoded by GNA11, and to date only two FHH2-associated Gα11 missense mutations (Leu135Gln and Ile200del) have been reported. FHH3 is the result of loss-of-function mutations of the adaptor protein-2 σ-subunit (AP2σ), which plays a pivotal role in clathrin-mediated endocytosis. We describe a 65-year-old woman who had hypercalcemia with normal circulating parathyroid hormone concentrations and hypocalciuria, features consistent with FHH, but she did not have CaSR and AP2σ mutations. Mutational analysis of the GNA11 gene was therefore undertaken, using leucocyte DNA, and this identified a novel heterozygous GNA11 mutation (c.161C>T; p.Thr54Met). The effect of the Gα11 variant was assessed by homology modeling of the related Gαq protein and by measuring the CaSR-mediated intracellular calcium (Ca2+i) responses of HEK293 cells, stably expressing CaSR, to alterations in extracellular calcium (Ca2+o) using flow cytometry. Three-dimensional modeling revealed the Thr54Met mutation to be located at the interface between the Gα11 helical and GTPase domains, and to likely impair GDP binding and interdomain interactions. Expression of wild-type and the mutant Gα11 in HEK293 cells stably expressing CaSR demonstrate that the Ca2+i responses after stimulation with Ca2+o of the mutant Met54 Gα11 led to a rightward shift of the concentration-response curve with a significantly (p < 0.01) increased mean half-maximal concentration (EC50) value of 3.88 mM (95% confidence interval [CI] 3.76–4.01 mM), when compared with the wild-type EC50 of 2.94 mM (95% CI 2.81–3.07 mM) consistent with a loss-of-function. Thus, our studies have identified a third Gα11 mutation (Thr54Met) causing FHH2 and reveal a critical role for the Gα11 interdomain interface in CaSR signaling and Ca2+o homeostasis. © 2016 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).
Effect of Lipopolysaccharide on Progesterone Production during Luteinization of Granulosa and Theca cells In Vitro
Authors: Shimizu Takashi , Echizenya Riku , Miyamoto Akio
Published: January 2016

The aim of this study is to examine the effect of lipopolysaccharide (LPS) on progesterone production during luteinization of granulosa and theca cells isolated from bovine large follicles. Granulosa and theca cells isolated from large follicles of bovine ovaries were exposed to LPS under appropriate hormone conditions in vitro. Progesterone (P4) production in theca cells, but not granulosa cells, was decreased by long‐term exposure of LPS. Long‐term exposure of LPS suppressed the gene expression of luteinizing hormone receptor in theca cells. Although long‐term exposure of LPS did not affect the expression of steroidogenic acute regulatory protein (StAR) and 3β‐hydroxy‐steroid dehydrogenase (3β‐HSD) genes, it did inhibit the protein expression of StAR and 3β‐HSD in theca cells. These findings suggest that theca cells, rather than granulosa cells, are susceptible to LPS during luteinization and that LPS inhibits P4 production by decreasing protein levels of StAR during luteinization of theca cells.
Presence of the Paternal Pronucleus Assists Embryo in Overcoming Cycloheximide Induced Abnormalities in Zygotic Mitosis
Authors: Ortega Michael A. , Ko Myungjun , Marh Joel , Finberg Ariel , Oshiro Marissa , Ward W. Steven
Published: January 2016

After fertilization, the maternal and paternal chromosomes independently proceed through pronuclear formation. These chromatin reconfigurations occur within a shared cytoplasm thus exposing both gametes to the same factors. Here, we report that continuous cycloheximide [40 μg/mL] treatment of parthenogenotes, androgenotes, and ICSI embryos reveals ORC2 pronuclear instability in the maternal (MPN) but not the paternal pronucleus (PPN). When released from CHX after 8 h, the MPN can recover ORC2 and proceed through replication, however, parthenogenotes encounter severe mitotic defects while both ICSI embryos and androgenotes are able to recover and develop at significantly higher rates. Taken together, these data suggest cycloheximide treatment promotes an environment that asymmetrically affects the stability of ORC2 on the MPN, and the ability of the MPN to develop. Furthermore, the presence of the PPN in the zygote can ameliorate both effects. These data suggest further evidence for crosstalk between the two pronuclei during the first cell cycle of the embryo. J. Cell. Biochem. 117: 1806–1812, 2016. © 2016 Wiley Periodicals, Inc.
Improvement of skeletal muscle performance in ageing by the metabolic modulator Trimetazidine
Authors: Ferraro Elisabetta , Pin Fabrizio , Gorini Stefania , Pontecorvo Laura , Ferri Alberto , Mollace Vincenzo , Costelli Paola , Rosano Giuseppe
Published: January 2016

Background

The loss of muscle mass (sarcopenia) and the associated reduced muscle strength are key limiting factors for elderly people's quality of life. Improving muscle performance does not necessarily correlate with increasing muscle mass. In fact, particularly in the elderly, the main explanation for muscle weakness is a reduction of muscle quality rather than a loss of muscle mass, and the main goal to be achieved is to increase muscle strength. The effectiveness of Trimetazidine (TMZ) in preventing muscle functional impairment during ageing was assessed in our laboratory.

Methods

Aged mice received TMZ or vehicle for 12 consecutive days. Muscle function was evaluated at the end of the treatment by a grip test as well as by an inverted screen test at 0, 5, 7 and 12 days of TMZ treatment. After sacrifice, muscles were stored for myofiber cross‐sectional area assessment and myosin heavy chain expression evaluation by western blotting.

Results

Chronic TMZ treatment does not affect the mass of both gastrocnemius and tibialis anterior muscles, while it significantly increases muscle strength. Indeed, both latency to fall and grip force are markedly enhanced in TMZ‐treated versus untreated mice. In addition, TMZ administration results in higher expression of slow myosin heavy chain isoform and increased number of small‐sized myofibers.

Conclusions

We report here some data showing that the modulation of skeletal muscle metabolism by TMZ increases muscle strength in aged mice. Reprogramming metabolism might therefore be a strategy worth to be further investigated in view of improving muscle performance in the elderly.
Click to Share: Patterns in Tourist Photography and Sharing
Authors: Konijn Esther , Sluimer Nienke , Mitas Ondrej
Published: January 2016

Differences between tourists in photographing and photo‐sharing behaviours have been under‐researched. We examined the influence of geographic origin and travel group composition on tourist photographing and sharing. Questionnaires were used to measure photographing and sharing frequency, while participant observation afforded a deeper examination of sharing processes. Findings showed differences in photography behaviour between solo and accompanied tourists. Tourists from some continents also took and shared photographs more frequently. Observations uncovered processes connecting sharing, photographing, and content of photographs. As user‐generated content becomes increasingly influential in tourism management, attention to origin, group composition and other individual differences can help engage tourists in photographing and sharing. Copyright © 2016 John Wiley & Sons, Ltd.
Capturing Process Knowledge and Measuring Systems' Cost Savings Through Business Activity Modeling and Activity‐Based Costing
Authors: Orwig Richard , Pendley John , Baker James , Flather William
Published: January 2016

The motivation for business change is to either improve the quality of products or services or decrease the costs of current operations that create those products or services. Because implementation of an information system causes business change, that implementation should demonstrate some explicit value in improvement of quality or decreased costs (or both). Quantifying the value provides justification for information systems implementation. Through a case study of four real‐world examples, this paper shows how time‐based activity costing determines costs associated with a set of business activities prior to a business change and then again after the implemented system. Four separate municipal organizations' business activity models were built prior to implementation of web‐based electronic payment systems and then after the implementation. Activity‐based costing analysis demonstrated benefits of reduced costs in a range from 15% to 28% in three cases. However, costs actually increased by 7% in a fourth case. In this fourth case, quality improvements were difficult to quantify, but workers felt that the increased costs were worth the changes in business activities. Copyright © 2015 John Wiley & Sons, Ltd.
Absorptive Capacity and Technology Knowledge: Enhancing Relational Capital
Authors: Vieira Carlos Lopez Cano , Briones‐Peñalver Antonio‐Juan , Cegarra‐Navarro Juan‐Gabriel
Published: January 2016

The purposes of this study are to examine the relationship between absorptive capacity and relational capital and to identify a potential stock of technology knowledge (T‐knowledge) that can act as a catalyst for these relationships. We also examine the relative importance and significance of ‘intentional unlearning’ as a bridge between ‘relational capital’ and ‘T‐knowledge’ and the existence and enhancement of relational capital. These relationships are examined through an empirical investigation of 125 Portuguese companies.

Portugal is facing an extremely difficult economic situation and thousands of jobs have been lost. As a result, the ability for organisations to create, transfer, assemble, integrate and use relational capital as leverage is fundamental to achieving a competitive advantage or, indeed, survival. Associação Empresarial da Região do Algarve (NERA) is a non‐profit organisation of an inter‐sectoral nature associated with the Portuguese Industrial Association representing the Algarve.

Analysis of the data indicates that if the organisation considers the establishment of a stock of T‐knowledge as a prior step to the enhancement of unlearning, then unlearning has a positive influence on the conditions that stimulate the enhancement of relational capital. Our main conclusion is that creation of relational capital by NERA members will depend to a significant extent on how managers acquire, analyse, interpret, and understand new external knowledge. Copyright © 2015 John Wiley & Sons, Ltd.
Algorithms and design strategies towards automated glycoproteomics analysis
Authors: Hu Han , Khatri Kshitij , Zaia Joseph
Published: January 2016

Glycoproteomics involves the study of glycosylation events on protein sequences ranging from purified proteins to whole proteome scales. Understanding these complex post‐translational modification (PTM) events requires elucidation of the glycan moieties (monosaccharide sequences and glycosidic linkages between residues), protein sequences, as well as site‐specific attachment of glycan moieties onto protein sequences, in a spatial and temporal manner in a variety of biological contexts. Compared with proteomics, bioinformatics for glycoproteomics is immature and many researchers still rely on tedious manual interpretation of glycoproteomics data. As sample preparation protocols and analysis techniques have matured, the number of publications on glycoproteomics and bioinformatics has increased substantially; however, the lack of consensus on tool development and code reuse limits the dissemination of bioinformatics tools because it requires significant effort to migrate a computational tool tailored for one method design to alternative methods. This review discusses algorithms and methods in glycoproteomics, and refers to the general proteomics field for potential solutions. It also introduces general strategies for tool integration and pipeline construction in order to better serve the glycoproteomics community. © 2016 Wiley Periodicals, Inc. Mass Spec Rev 36:475–498, 2017
Intraventricular Baclofen for Treatment of Severe Dystonia Associated with Glutaryl‐CoA Dehydrogenase Deficiency (GA1): Report of Two Cases
Authors: Ghatan Saadi , Kokoszka Malgosia A. , Ranney Anne M. , Strauss Kevin A.
Published: January 2016

Two individuals with intractable generalized dystonia secondary to glutaric aciduria type 1 (GA1) were treated with continuous intraventricular baclofen (IVB) infusion. On IVB of 220 μg/day, one 10‐year‐old girl had an 85% reduction in dystonia, from Barry‐Albright Dystonia Scale (BADS) score 30.7 to 4.5 (maximum score: 32) at 30 postoperative months. Her enteral dystonia medications were reduced >60%, and she discontinued medications for pain, anxiety, and depression. A second GA1 patient, age 23, experienced a more modest 18% reduction in dystonia (BADS decrease from 29.7 to 24.3) on IVB of 1,665 μg/day at 14 postoperative months. He substantially reduced his enteral dystonia medications and reported meaningful pain relief. These cases demonstrate that IVB may be a palliative option in the intractable dystonia of GA1. Our provisional observations suggest that IVB may be more beneficial in younger GA1 patients.
Amyloid‐Beta Positron Emission Tomography Imaging of Alzheimer's Pathology in Parkinson's Disease Dementia
Authors: Akhtar Rizwan S. , Xie Sharon X. , Brennan Laura , Pontecorvo Michael J. , Hurtig Howard I. , Trojanowski John Q. , Weintraub Daniel , Siderowf Andrew D.
Published: January 2016

Background

Neuronal loss and alpha‐synuclein (α‐syn) pathology are diagnostic of PD in the appropriate clinical context. However, some Parkinson's disease (PD) patients have comorbid Alzheimer's disease (AD) pathology on autopsy, including amyloid‐beta (Aβ) plaques and neurofibrillary tangles. Florbetapir (18F) is a PET ligand that detects Aβ pathology. We hypothesized that florbetapir (18F) imaging could detect Aβ pathology in PD dementia (PDD) patients before death. The aim of this study was to determine the utility of florbetapir (18F) PET imaging in detecting Aβ pathology in patients with autopsy‐confirmed PDD.

Methods

Five participants with PDD had florbetapir (18F) PET imaging before death as a part of a longitudinal research study of cognitive decline in PD. PET scans were evaluated by expert raters blinded to clinical and neuropathological information. At autopsy, all 5 participants underwent semiquantitative assessments of regional Aβ and tau immunohistochemistry.

Results

All participants met neuropathological criteria for PD. Two had both positive florbetapir (18F) scans and Aβ‐positive plaques in multiple brain regions. Regional florbetapir (18F) binding correlated with regional semiquantitative Aβ pathology in these cases. Three cases had negative florbetapir (18F) scans. Two of these had significant tau pathology without Aβ pathology, consistent with PSP in 1 case and argyrophilic grain disease in the other. The last case had a low level of AD neuropathological change.

Conclusions

Florbetapir (18F) Aβ imaging can detect the presence of Aβ neuropathology in patients with PDD. This imaging technique may aid the clinical evaluation of PDD patients to determine whether cognitive decline is occurring in the setting of Aβ accumulation.
Acceleration of MR parameter mapping using annihilating filter‐based low rank hankel matrix (ALOHA)
Authors: Lee Dongwook , Jin Kyong Hwan , Kim Eung Yeop , Park Sung‐Hong , Ye Jong Chul
Published: January 2016

Purpose

MR parameter mapping is one of clinically valuable MR imaging techniques. However, increased scan time makes it difficult for routine clinical use. This article aims at developing an accelerated MR parameter mapping technique using annihilating filter based low‐rank Hankel matrix approach (ALOHA).

Theory

When a dynamic sequence can be sparsified using spatial wavelet and temporal Fourier transform, this results in a rank‐deficient Hankel structured matrix that is constructed using weighted k‐t measurements. ALOHA then utilizes the low rank matrix completion algorithm combined with a multiscale pyramidal decomposition to estimate the missing k‐space data.

Methods

Spin‐echo inversion recovery and multiecho spin echo pulse sequences for T1 and T2 mapping, respectively, were redesigned to perform undersampling along the phase encoding direction according to Gaussian distribution. The missing k‐space is reconstructed using ALOHA. Then, the parameter maps were constructed using nonlinear regression.

Results

Experimental results confirmed that ALOHA outperformed the existing compressed sensing algorithms. Compared with the existing methods, the reconstruction errors appeared scattered throughout the entire images rather than exhibiting systematic distortion along edges and the parameter maps.

Conclusion

Given that many diagnostic errors are caused by the systematic distortion of images, ALOHA may have a great potential for clinical applications. Magn Reson Med 76:1848–1864, 2016. © 2016 International Society for Magnetic Resonance in Medicine
Nano silicon carbide embodied soy protein bionanocomposites
Authors: Sarkar Niladri , Sahoo Gyana R. , Swain Sarat K.
Published: January 2016

Soy protein bionanocomposites were prepared by dispersion of silicon carbide (SiC) nanoparticles into the soy protein matrix through cost effective green technique. The chemical interaction of SiC and soy protein was studied due to the electronic interaction of delocalized lone pair of N atom of free and bonded –NH2 groups of the protein chain with the vacant d‐orbital of Si atom of SiC, which was verified from Fourier transform infrared spectroscopy (FTIR). The surface morphology of the prepared bionanocomposites was investigated by field emission scanning electron microscope (FESEM); whereas the dispersion of nano‐sized SiC within soy protein was viewed from high resolution transmission electron microscope (HRTEM). Crystalline nature of the bionanocomposites was investigated from X‐ray diffraction (XRD) study and selected area electron diffraction (SAED) pattern. Thermal stability and chemical resistivity of the designed soy protein were substantially more than the virgin soy protein, with little scarification in biodegradability. The superior thermal and mechanical stability in along with chemical resistivity may enable the bionanocomposite materials for packaging applications. POLYM. COMPOS., 38:E57–E65, 2017. © 2016 Society of Plastics Engineers
Preparation, properties of In‐situ silica modified styrene‐butadiene rubber and its silica‐filled composites
Authors: Yin Changjie , Zhang Qiuyu , Liu Jianxun , Liu Lvling , Gu Junwei
Published: January 2016

In this work, native emulsion polymerization styrene butadiene rubber (SBR) were first grafted by vinyltriethoxysilane (VTES) to SBR‐g‐VTES (VTES grafted SBR), second, the SBR‐g‐VTES were modified by different amount of TEOS (tetraethoxysilane) using in situ sol‐gel method, at the last, the extra silica was added into the in situ modified SBR system to get the modified SBR/silica composites using latex coagulation technology. The effect of different amount of TEOS on modified SBR/silica composites was also systematically studied, including the content of silica and utilization of silica, cure characteristics, physical mechanical properties and dynamic mechanical properties. The surface properties of modified SBR/silica composites were characterized by scanning electron microscope (SEM). It can be got that the grafting of VTES and in situ hydrolysis and condensation of TEOS can effectively inhibit the agglomeration and improve the mechanical properties of modified SBR/silica. It also can be found that modified SBR brings well physical and dynamic mechanical properties, wear resistance, and low rolling resistance to SBR, especially, when the TEOS is 3.0 g, the best overall performance of modified SBR/silica can be achieved. POLYM. COMPOS., 39:22–28, 2018. © 2016 Society of Plastics Engineers
Nonisothermal and isothermal crystallization behavior of isotactic polypropylene/chemically reduced graphene nanocomposites
Authors: Tang Dahang , Li Songrong , Yang Junlong , Su Juqiao , Yang Qi , Kong Miqiu , Huang Yajiang , Liao Xia
Published: January 2016

Graphene oxide was firstly prepared by a modified Hummers method and then reduced via hydrazine reduction method to obtain chemically reduced graphene (CRG). The morphology of CRG dispersed in the isotactic polypropylene (iPP) matrix was observed using transmission electron microscope and rheological measurement methods. Nonisothermal and isothermal crystallization behaviors of iPP/CRG nanocomposites were investigated by differential scanning calorimetry and polarizing optical microscopy methods, respectively. Nonisothermal crystallization measurement revealed that CRG elevated the crystallization temperature of iPP due to the nucleating effect of CRG. And during isothermal crystallization process, the half time crystallization of nanocomposites was significantly reduced. Furthermore, the images of polarized optical microscopy also exhibited that the nucleation density of nanocomposites was much higher than that of neat iPP due to the heterogeneous nucleation of CRG even at a loading of 0.5%. POLYM. COMPOS., 38:E342–E350, 2017. © 2016 Society of Plastics Engineers
A predictive parameter for the shape memory behavior of thermoplastic polymers
Authors: Xiao Rui , Yakacki Christopher M. , Guo Jingkai , Frick Carl P. , Nguyen Thao D.
Published: January 2016

We present an experimental and modeling study of the effect of programming conditions on the shape‐memory behaviors of amorphous thermoplastic polymers. Experimentally we measure the influence of deformation temperature, strain rate and relaxation time on the thermomechanical properties and shape‐memory response of poly(para‐phenylene), which is a stiff and strong aromatic thermoplastic. To understand the underlying mechanism, we develop a viscoelastic model, which contains multiple discrete relaxation processes with broad distribution of relaxation time. The model parameters of the relaxation spectrum are obtained from the master curve of small strain–stress relaxation tests using time‐temperature superposition. The model predictions show good agreement with experimental observations, including the stress response and shape‐memory response under various conditions. We applied the model to study the effect of the programming conditions on the shape recovery performance. The results show that the relaxation modulus at the end of the programming process was a predictor of the recovery speed and recoverable strain ratio. This provides a design metric to optimize the shape programming process for shape recovery. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys.2016,54, 1405–1414
Electronic and optical properties of MX3 (M = Ti, Zr and Hf; X = S, Se) structures: A first principles insight
Authors: Abdulsalam Mahmud , Joubert Daniel P.
Published: January 2016

Abstractauthoren Abstractauthoren The electronic and optical properties of semiconducting TiS3, HfS3, HfSe3, ZrS3, and ZrSe3 with structure P21/m have been investigated for the first time at the and BSE level of approximations, respectively. The structures were relaxed using PBE with the inclusion of van der Waal's correction terms to account for long‐range dispersion forces, which is a necessary ingredient in predicting an accurate description of structural properties of layered systems. In order to predict reasonable estimates of the electronic properties, MBJ, HSE06, and were used to calculate the fundamental band gaps of the structures and the Bethe–Salpeter equation (BSE) was solved to obtain an accurate description of the optical properties of the compounds. It is found that the compounds have band gaps between 0.58 to 2.17 eV. Their optical absorption spectra revealed that they start to absorb light in the range of 0.9–1.63 eV making them potential materials for third‐generation solar photovoltaic applications and possible photo‐catalysis applications.