bluuebunny/crossref_metadata_2025 huggingface dataset:
Free Radical Processes in Non-enzymatic Browning of Glucose and Lysine: Influence of Temperature and Unsaturated Lipids
Authors: Hedegaard Rikke V. , Santos Cecile , Yin Thoo Yin , Skibsted Leif H.
Published: February 2014

Formation of dialkylpyrazinium radical cations in aerated 70 % aqueous glycerol solutions of glucose and lysine during heating resulting in browning (90, 110, and 130°C, investigated) was more dependent on temperature than formation of brown colour. Activation energy (Ea) for radical formation was ~83 kJ mol–1, compared with ~70 kJ mol–1 for browning, and was unaffected by methyl linolenate. Low-temperature browning was influenced by non-radical degradation of Amadori products, whereas radical processes were prominent at higher temperatures and were unaffected by unsaturated lipids. In contrast, methyl linolenate reacts with lysine in the absence of glucose to form fluorescent products at a slow rate (Ea 25 kJ mol–1). Glucose increased the rate of formation of fluorescent products (Ea ~60 kJ mol–1), in agreement with Maillard reactions at low temperatures involving glucose as a rate-determining reagent. Lipid oxidation does not have a direct effect on lysine and glucose browning reactions at conditions relevant for food; effects of lipids on Maillard reactions are matrix-related.
[Tris(alkoxydimethylsilyl)methyl]alkylferrocenes as New Ferrocenyl Multifunctional Silyl Ethers
Authors: Safa Kazem D. , Abbasi Hassan , Teimuri-Mofrad Reza , Charandabi Farzaneh A.
Published: February 2014

[Tris(trimethylsilyl)methyl]alkylferrocenes and [tris(dimethylsilyl)methyl]alkylferrocenes were synthesized by treatment of tris(trimethylsilyl)methyllithium and tris(dimethylsilyl)methyllithium in THF with 3-bromopropylferrocene or 4-bromobutylferrocene at 0°C. [Tris(alkoxydimethylsilyl)methyl]alkylferrocenes were obtained by dehydrocoupling with various aliphatic and benzylic alcohols in the presence of the Karstedt catalyst (platinum(0)-1,3-divinyl-1,1,3,3-tetramethyldisiloxane in xylene) in good to excellent yields. 4-[Tris(benzyloxydimethylsilyl)methyl]butylferrocene was also prepared from the transetherification of 4-[tris(methoxydimethylsilyl)methyl]butylferrocene with benzyl alcohol in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene as catalyst.
Drought-tolerance QTLs commonly detected in two sets of reciprocal introgression lines in rice
Authors: Wang Yun , Zhang Qiang , Zheng Tianqing , Cui Yanru , Zhang Wenzhong , Xu Jianlong , Li Zhikang
Published: February 2014

Drought is one of the major abiotic stresses limiting rice (Oryza sativa L.) production. Quantitative trait loci (QTLs) for drought tolerance (DT) at the reproductive stage were identified with two sets of reciprocal introgression lines derived from Lemont × Teqing. In total, 29 and 23 QTLs were identified in the Teqing and Lemont backgrounds, respectively, during the reproductive stage under drought and irrigated conditions for spikelet number per panicle, seed fertility, filled grain weight per panicle, plant height, and grain yield per plant. Most of these QTLs showed obvious differential expressions in response to drought stress. Another 21 QTLs were detected by the ratio of trait values under drought stress relative to the normal irrigation conditions in the two backgrounds. For 28 DT QTLs, the Teqing alleles at 23 loci had increased trait values and could improve DT under drought stress. Only five (17.9%) DT QTLs (QSnp1b, QSnp3a, QSnp11, QSf8, and QGyp2a) were consistently detected in the two backgrounds, clearly suggesting overwhelming genetic background effects on QTL detection for DT. Seven of the DT QTL regions identified were found to share the same genomic regions with previously reported DT-related genes. Introgressing or pyramiding of favourable alleles from Teqing at the validated QTLs (QSnp3a, QSnp11 and QGyp2a) into Lemont background may improve DT level of Lemont.
The signaling lipid PI(3,5)P2stabilizes V1–Vosector interactions and activates the V-ATPase
Authors: Li Sheena Claire , Diakov Theodore T. , Xu Tao , Tarsio Maureen , Zhu Wandi , Couoh-Cardel Sergio , Weisman Lois S. , Kane Patricia M.
Published: February 2014

Vacuolar proton-translocating ATPases (V-ATPases) are highly conserved, ATP-driven proton pumps regulated by reversible dissociation of its cytosolic, peripheral V1domain from the integral membrane Vodomain. Multiple stresses induce changes in V1-Voassembly, but the signaling mechanisms behind these changes are not understood. Here we show that certain stress-responsive changes in V-ATPase activity and assembly require the signaling lipid phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2). V-ATPase activation through V1-Voassembly in response to salt stress is strongly dependent on PI(3,5)P2synthesis. Purified Vocomplexes preferentially bind to PI(3,5)P2on lipid arrays, suggesting direct binding between the lipid and the membrane sector of the V-ATPase. Increasing PI(3,5)P2levels in vivo recruits the N-terminal domain of Vo-sector subunit Vph1p from cytosol to membranes, independent of other subunits. This Vph1p domain is critical for V1-Vointeraction, suggesting that interaction of Vph1p with PI(3,5)P2-containing membranes stabilizes V1-Voassembly and thus increases V-ATPase activity. These results help explain the previously described vacuolar acidification defect in yeast fab1∆ and vac14∆ mutants and suggest that human disease phenotypes associated with PI(3,5)P2loss may arise from compromised V-ATPase stability and regulation.
How should we be selecting our graduate students?
Authors: Weiner Orion D.
Published: February 2014

We use many quantitative undergraduate metrics to help select our graduate students, but which of these usefully discriminate successful from underperforming students and which should be ignored? Almost everyone has his or her own pet theory of the most predictive criteria, but I hoped to address this question in a more unbiased manner. I conducted a retrospective analysis of the highest- and lowest-ranked graduate students over the past 20 years in the Tetrad program at the University of California at San Francisco to identify undergraduate metrics that significantly differed between these groups. Only the number of years of research experience and subject graduate record exams (GREs) were strong discriminators between the highest- and lowest-ranked students, whereas many other commonly used admissions metrics (analytical, verbal, and quantitative GREs, grade point average, and ranking of undergraduate institution) showed no correlation with graduate performance. These are not necessarily the same criteria that matter at other graduate programs, but I would urge faculty elsewhere to conduct similar analyses to improve the admissions process and to minimize the use of useless metrics in selecting our students.
Resistance of the Defeated: German and Italian Big Business and the American Antitrust Policy, 1945–1957
Authors: Segreto Luciano , Wubs Ben
Published: February 2014

The article addresses the question to what extent American antitrust policy in Germany and Italy during the 1950s, was a success or not. Did these nations adopt this policy, did they adapt themselves to it, or did they completely reject it? By a detailed comparison of these two big European nations, Germany and Italy—both defeated powers of the Second World War, and both therefore strongly dependent on postwar American aid—the effects of the American antitrust policy will be analyzed. Eventually, the Germans better adapted, after initial resistance of German big business, to the American plans than the Italians, however, only in an amended and softer form. The Italian resistance—but we even use the expression prolonged rejection—to the economic reforms were much stronger. The US administration envisioned a unified free European market without cartels as early as 1943, however, it would take another fifty years before these ideas would be implemented.
Bilateral Suprazygomatic Maxillary Nerve Block for Cleft Palate Repair in Children
Authors: Chiono Julien , Raux Olivier , Bringuier Sophie , Sola Chrystelle , Bigorre Michèle , Capdevila Xavier , Dadure Christophe
Published: February 2014

Background:

The authors investigated the efficacy of bilateral suprazygomatic maxillary nerve block (SMB) for postoperative pain relief in infants undergoing cleft palate repair.

Methods:

In this prospective, double-blind, single-site, randomized, and parallel-arm controlled trial, 60 children were assigned to undergo bilateral SMB with general anesthesia with either 0.15 ml/kg of 0.2% ropivacaine (Ropi group) or 0.15 ml/kg of isotonic saline (Saline group) on each side. The primary endpoint was total postoperative morphine consumption at 48 h. Pain scores and respiratory- and SMB-related complications were noted.

Results:

The overall dose of intravenous morphine after 48 h (mean [95% CI]) was lower in the Ropi group compared with that in the Saline group (104.3 [68.9 to 139.6] vs. 205.2 [130.7 to 279.7] μg/kg; P = 0.033). Continuous morphine infusion was less frequent in the Ropi group compared with that in the Saline group (1 patient [3.6%] vs. 9 patients [31%]; P = 0.006). Three patients in the Saline group had an episode of oxygen desaturation requiring oxygen therapy. There were no technical failures or immediate complications of the SMB. Intraoperative hemodynamic parameters, doses of sufentanil, pain scores, and postoperative hydroxyzine requirements were not different between the two groups.

Conclusion:

Bilateral SMB is an easy regional anesthesia technique that reduces total morphine consumption at 48 h after cleft palate repair in children and the use of continuous infusion of morphine and may decrease postoperative respiratory complications.
Endothelial Barrier Protection by Local Anesthetics
Authors: Piegeler Tobias , Votta-Velis E. Gina , Bakhshi Farnaz R. , Mao Mao , Carnegie Graeme , Bonini Marcelo G. , Schwartz David E. , Borgeat Alain , Beck-Schimmer Beatrice , Minshall Richard D.
Published: February 2014

Background:

Pulmonary endothelial barrier dysfunction mediated in part by Src-kinase activation plays a crucial role in acute inflammatory disease. Proinflammatory cytokines, such as tumor necrosis factor-α (TNFα), activate Src via phosphatidylinositide 3-kinase/Akt-dependent nitric oxide generation, a process initiated by recruitment of phosphatidylinositide 3-kinase regulatory subunit p85 to TNF-receptor-1. Because amide-linked local anesthetics have well-established anti-inflammatory effects, the authors hypothesized that ropivacaine and lidocaine attenuate inflammatory Src signaling by disrupting the phosphatidylinositide 3-kinase–Akt–nitric oxide pathway, thus blocking Src-dependent neutrophil adhesion and endothelial hyperpermeability.

Methods:

Human lung microvascular endothelial cells, incubated with TNFα in the absence or presence of clinically relevant concentrations of ropivacaine and lidocaine, were analyzed by Western blot, probing for phosphorylated/activated Src, endothelial nitric oxide synthase, Akt, intercellular adhesion molecule-1, and caveolin-1. The effect of ropivacaine on TNFα-induced nitric oxide generation, co-immunoprecipitation of TNF-receptor-1 with p85, neutrophil adhesion, and endothelial barrier disruption were assessed.

Results:

Ropivacaine and lidocaine attenuated TNFα-induced Src activation (half-maximal inhibitory concentration [IC50] = 8.611 × 10−10 M for ropivacaine; IC50 = 5.864 × 10−10 M for lidocaine) and endothelial nitric oxide synthase phosphorylation (IC50 = 7.572 × 10−10 M for ropivacaine; IC50 = 6.377 × 10−10 M for lidocaine). Akt activation (n = 7; P = 0.006) and stimulus-dependent binding of TNF-receptor-1 and p85 (n = 6; P = 0.043) were blocked by 1 nM of ropivacaine. TNFα-induced neutrophil adhesion and disruption of endothelial monolayers via Src-dependent intercellular adhesion molecule-1- and caveolin-1-phosphorylation, respectively, were also attenuated.

Conclusions:

Ropivacaine and lidocaine effectively blocked inflammatory TNFα signaling in endothelial cells by attenuating p85 recruitment to TNF-receptor-1. The resultant decrease in Akt, endothelial nitric oxide synthase, and Src phosphorylation reduced neutrophil adhesion and endothelial hyperpermeability. This novel anti-inflammatory “side-effect” of ropivacaine and lidocaine may provide therapeutic benefit in acute inflammatory disease.
CUL4A ubiquitin ligase: a promising drug target for cancer and other human diseases
Authors: Sharma Puneet , Nag Alo
Published: February 2014

The ability of cullin 4A (CUL4A), a scaffold protein, to recruit a repertoire of substrate adaptors allows it to assemble into distinct E3 ligase complexes to mediate turnover of key regulatory proteins. In the past decade, a considerable wealth of information has been generated regarding its biology, regulation, assembly, molecular architecture and novel functions. Importantly, unravelling of its association with multiple tumours and modulation by viral proteins establishes it as one of the key proteins that may play an important role in cellular transformation. Considering the role of its substrate in regulating the cell cycle and maintenance of genomic stability, understanding the detailed aspects of these processes will have significant consequences for the treatment of cancer and related diseases. This review is an effort to provide a broad overview of this multifaceted ubiquitin ligase and addresses its critical role in regulation of important biological processes. More importantly, its tremendous potential to be exploited for therapeutic purposes has been discussed.
Description of a Gram-negative bacterium, Sphingomonas guangdongensis sp. nov.
Authors: Feng Guang-Da , Yang Song-Zhen , Wang Yong-Hong , Zhang Xiu-Xiu , Zhao Guo-Zhen , Deng Ming-Rong , Zhu Hong-Hui
Published: February 2014

A Gram-stain-negative bacterial strain, designated 9NM-8T, was isolated from an abandoned lead-zinc ore in Mei county, Meizhou, Guangdong province, PR China. The isolate was orange-pigmented, aerobic, oxidase- and catalase-positive, motile with lophotrichous flagella and rod-shaped. Strain 9NM-8Tgrew optimally at pH 7.0 and 30 °C and in the absence of NaCl on R2A agar. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 9NM-8Tbelongs to the genusSphingomonas, with highest sequence similarities toSphingomonas azotifigensKACC 14484T(96.1 %),Sphingomonas trueperiDSM 7225T(96.0 %) andSphingomonas pituitosaDSM 13101T(95.6 %). Strain 9NM-8Tcontained Q-10 as the predominant ubiquinone. The major fatty acids included C18 : 1ω7c, C16 : 0, C16 : 1ω7cand/or C16 : 1ω6c(summed feature 3) and 11-methyl C18 : 1ω7c. The DNA G+C content was 69.6±1.3 mol%. The major component in the polyamine pattern wassym-homospermidine and the polar lipid profile contained sphingoglycolipid, phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, an unidentified glycolipid and two unidentified phospholipids. Based on comparative analysis of physiological, chemotaxonomic and phylogenetic characteristics, strain 9NM-8Tshould be considered to represent a novel species of the genusSphingomonas, for which the nameSphingomonas guangdongensissp. nov. is proposed. The type strain is 9NM-8T( = GIMCC 1.653T = CGMCC 1.12672T = DSM 27570T).
Relationship between the severity of acne vulgaris and antimicrobial resistance of bacteria isolated from acne lesions in a hospital in Japan
Authors: Nakase Keisuke , Nakaminami Hidemasa , Takenaka Yuko , Hayashi Nobukazu , Kawashima Makoto , Noguchi Norihisa
Published: February 2014

Propionibacterium acnes and Staphylococcus epidermidis are normal skin inhabitants that are frequently isolated from lesions caused by acne, and these micro-organisms are considered to contribute to the inflammation of acne. In the present study, we examined the antimicrobial susceptibilities and resistance mechanisms of P. acnes and S. epidermidis isolated from patients with acne vulgaris in a university hospital in Japan from 2009 to 2010. Additionally, we analysed the relationship between the antimicrobial resistance of P. acnes and the severity of acne vulgaris. Some P. acnes strains (18.8 %; 13/69) were resistant to clindamycin. All strains had a mutation in the 23S rRNA gene, except for one strain that expressed erm(X) encoding a 23S rRNA methylase. Tetracycline-resistant P. acnes strains were found to represent 4.3 % (3/69) of the strains, and this resistance was caused by a mutation in the 16S rRNA gene. Furthermore, three strains with reduced susceptibility to nadifloxacin (MIC = 16 µg ml−1) were detected. When analysing the correlation between the antimicrobial resistance of P. acnes and S. epidermidis, more than 80 % of the patients who carried clindamycin-resistant P. acnes also carried clindamycin-resistant S. epidermidis. However, no epidemic strain that exhibited antimicrobial resistance was detected in the P. acnes strains when analysed by PFGE. Therefore, our results suggest that the antimicrobial resistance of P. acnes is closely related to antimicrobial therapy. Additionally, those P. acnes strains tended to be frequently found in severe acne patients rather than in mild acne patients. Consequently, the data support a relationship between using antimicrobial agents and the emergence of antimicrobial resistance.
Genomic V-gene repertoire in reptiles
Authors: Olivieri David N. , von Haeften Bernardo , Sánchez-Espinel Christian , Faro Jose , Gambón-Deza Francisco
Published: February 2014

Reptiles and mammals diverged over 300 million years ago, creating two parallel evolutionary lineages amongst terrestrial vertebrates. In reptiles, two main evolutionary lines emerged, one gave rise to Squamata, while the other gave rise to Testudines, Crocodylia and birds. In this study, we determined the genomic variable (V)-gene repertoire in reptiles corresponding to the three main immunoglobulin (Ig) loci and the four main T-cell receptor (TCR) loci. We show that squamata lack the TCRγ/δgenes and snakes lack the Vκgenes. In representative species of testudines and crocodiles, the seven major Ig and TCR loci are maintained. As in mammals, genes of the Ig loci can be grouped into well-defined clans through a multi-species phylogenetic analysis. We show that the reptile VH and Vλgenes are distributed amongst the established mammalian clans, while their Vκgenes are found within a single clan, nearly exclusive from the mammalian sequences. The reptile and mammal V-genes of the TRA locus cluster into six common evolutionary clans. In contrast, the reptile V-genes from the TRB locus cluster into three clans, which have few mammalian members. In this locus, the V-gene sequences from mammals appear to have undergone different evolutionary diversification processes that occurred outside these shared reptile clans.
Elements Required for an Efficient NADP-Malic Enzyme Type C4 Photosynthesis
Authors: Wang Yu , Long Stephen P. , Zhu Xin-Guang
Published: February 2014

C4 photosynthesis has higher light, nitrogen, and water use efficiencies than C3 photosynthesis. Although the basic anatomical, cellular, and biochemical features of C4 photosynthesis are well understood, the quantitative significance of each element of C4 photosynthesis to the high photosynthetic efficiency are not well defined. Here, we addressed this question by developing and using a systems model of C4 photosynthesis, which includes not only the Calvin-Benson cycle, starch synthesis, sucrose synthesis, C4 shuttle, and CO2 leakage, but also photorespiration and metabolite transport between the bundle sheath cells and mesophyll cells. The model effectively simulated the CO2 uptake rates, and the changes of metabolite concentrations under varied CO2 and light levels. Analyses show that triose phosphate transport and CO2 leakage can help maintain a high photosynthetic rate by balancing ATP and NADPH amounts in bundle sheath cells and mesophyll cells. Finally, we used the model to define the optimal enzyme properties and a blueprint for C4 engineering. As such, this model provides a theoretical framework for guiding C4 engineering and studying C4 photosynthesis in general.
Pathway-Level Acceleration of Glycogen Catabolism by a Response Regulator in the Cyanobacterium Synechocystis Species PCC 6803
Authors: Osanai Takashi , Oikawa Akira , Numata Keiji , Kuwahara Ayuko , Iijima Hiroko , Doi Yoshiharu , Saito Kazuki , Hirai Masami Yokota
Published: February 2014

Response regulators of two-component systems play pivotal roles in the transcriptional regulation of responses to environmental signals in bacteria. Rre37, an OmpR-type response regulator, is induced by nitrogen depletion in the unicellular cyanobacterium Synechocystis species PCC 6803. Microarray and quantitative real-time polymerase chain reaction analyses revealed that genes related to sugar catabolism and nitrogen metabolism were up-regulated by rre37 overexpression. Protein levels of GlgP(slr1367), one of the two glycogen phosphorylases, in the rre37-overexpressing strain were higher than those of the parental wild-type strain under both nitrogen-replete and nitrogen-depleted conditions. Glycogen amounts decreased to less than one-tenth by rre37 overexpression under nitrogen-replete conditions. Metabolome analysis revealed that metabolites of the sugar catabolic pathway and amino acids were altered in the rre37-overexpressing strain after nitrogen depletion. These results demonstrate that Rre37 is a pathway-level regulator that activates the metabolic flow from glycogen to polyhydroxybutyrate and the hybrid tricarboxylic acid and ornithine cycle, unraveling the mechanism of the transcriptional regulation of primary metabolism in this unicellular cyanobacterium.
A Calcium-Independent Activation of the Arabidopsis SOS2-Like Protein Kinase24 by Its Interacting SOS3-Like Calcium Binding Protein1
Authors: Lin Huixin , Du Wenming , Yang Yongqing , Schumaker Karen S. , Guo Yan
Published: February 2014

The salt stress-induced SALT-OVERLY-SENSITIVE (SOS) pathway in Arabidopsis (Arabidopsis thaliana) involves the perception of a calcium signal by the SOS3 and SOS3-like CALCIUM-BINDING PROTEIN8 (SCaBP8) calcium sensors, which then interact with and activate the SOS2 protein kinase, forming a complex at the plasma membrane that activates the SOS1 Na+/H+ exchanger. It has recently been reported that phosphorylation of SCaBP proteins by SOS2-like protein kinases (PKSs) stabilizes the interaction between the two proteins as part of a regulatory mechanism that was thought to be common to all SCaBP and PKS proteins. Here, we report the calcium-independent activation of PKS24 by SCaBP1 and show that activation is dependent on interaction of PKS24 with the C-terminal tail of SCaBP1. However, unlike what has been found for other PKS-SCaBP pairs, multiple amino acids in SCaBP1 are phosphorylated by PKS24, and this phosphorylation is dependent on the interaction of the proteins through the PKS24 FISL motif and on the efficient activation of PKS24 by the C-terminal tail of SCaBP1. In addition, we show that Thr-211 and Thr-212, which are not common phosphorylation sites in the conserved PFPF motif found in most SCaBP proteins, are important for this activation. Finally, we also found that SCaBP1-regulated PKS24 kinase activity is important for inactivating the Arabidopsis plasma membrane proton-translocating adenosine triphosphatase. Together, these results suggest the existence of a novel SCaBP-PKS regulatory mechanism in plants.
The dangers of the day of birth
Authors: Walker KF , Cohen AL , Walker SH , Allen KM , Baines DL , Thornton JG
Published: February 2014

Objective

To compare the risk of fetal death on the day of childbirth, with the risk of death at other ages, and with the risks of some hazardous activities, on a common scale of risk per day.

Design

Review of publicly available data.

Setting

UK.

Sample

Data extracted from the Office of National Statistics and other sources.

Methods

Data from the Office of National Statistics and other sources were used to calculate death rates at different ages expressed as rates per day of life. Death rates for different activities were also calculated as risks per day, or risks per activity, as appropriate. All risks were expressed in micromorts, the number of one in a million chances of dying. Figures on life expectancy (LE) were used to compare potential life years lost.

Main outcome measures

Daily, or unit of activity, risk of dying for different activities compared with the risk of dying on the day of childbirth.

Results

The risk of dying on the day of birth (0.43 per 1000, or 430 micromorts) exceeds that of any other average day of life until the 92nd year. It is comparable with other apparently more dangerous activities, such as undergoing major surgery. For comparison, the average risk of non‐natural death per day and the increased risk from smoking one cigarette or travelling 200 miles by car are all about 1 micromort.

Conclusions

The lifetime risk of death in childbirth is low, but is concentrated in a short period, making being born a high‐risk activity. Parents considering interventions to reduce these risks should be made aware of this.
Differential expression of natural killer activating and inhibitory receptors in patients with newly diagnosed systemic lupus erythematosus
Authors: Ye Zhuang , Ma Ning , Zhao Ling , Jiang Zhen‐Yu , Jiang Yan‐Fang
Published: February 2014

Aim

Systemic lupus erythematosus (SLE) presents as the abnormal activation and over‐proliferation of immune competent cells. Few studies have characterized the role of natural killer (NK) and NK T (NKT) cells in the pathogenesis of SLE, and therefore a consensus has not been reached as yet.

Method

Thirty‐two patients with new‐onset SLE and 15 healthy controls were recruited. Activated and inhibitory NK and NKT cells in peripheral blood were quantified by flow cytometry. The proportions of spontaneous and stimulated interferon (IFN)‐γ+ NK and NKT cells and CD107a+ NK cells was examined. Finally, the potential relationship between the cell subsets and clinical indexes was analyzed.

Results

The proportions of NK and NKT cells (P = 0.002 and 0.004, respectively) as well as the proportions of NKG2C+ NK cells, inhibitory NK and NKT cell subsets (P = 0.016, P = 0.019, P = 0.049, and P = 0.028, respectively) in SLE patients were significantly lower than those in controls. In contrast, the proportions of activated NK cells and NKT cell subsets were significantly higher (P = 0.036, P = 0.034, P = 0.005, and P = 0.007, respectively). Moreover, the proportions of stimulated IFN‐γ+ NKT cells were significantly higher than in the controls, and the proportions of stimulated CD107a+ NKT cells in SLE patients were significantly lower than in the controls (P = 0.032 and P = 0.02, respectively).

Conclusion

Lower proportions of NK and NKT cells, higher proportions of activated NK cells and activated NKT cells, lower proportions of inhibitory NK and NKT cells, higher NKT cell activity, and lower NKT cell degranulation may induce the autoimmune reaction involved in the pathogenesis of SLE.
Factors associated with winged forms of soybean aphid and an examination of North American spatial dynamics of this species in the context of migratory behaviour
Authors: Bahlai Christine A. , Schaafsma Arthur W. , Lagos Doris , Voegtlin David , Smith Jocelyn L. , Andrew Welsman J. , Xue Yingen , DiFonzo Christina , Hallett Rebecca H.
Published: February 2014

Soybean aphid is a severe invasive pest of soybeans in North America. From 2005 onward, a network of 47 suction traps in North America, each approximately 7 m in height, has monitored aerial populations of this species.

Suction trap captures of alate viviparous Aphis glycines in summer, and gynoparae and males in the autumn, were subjected to negative binomial regressions with environmental parameters. Models were ranked by using information‐theoretic methods to determine which parameters best explained aerial density of aphids. Multiparameter models incorporating the best parameters were constructed.

Best‐fit models were used to compute peak values of each parameter, where a quadratic relationship between captures and that parameter occurred. Data were subjected to non‐metric multidimensional scaling and analysis of similarity to observe patterns in the geographical and temporal distribution of captures.

Summer flight activity A. glycines was explained best by the level of aphid infestation in fields local to the trapping site, although the autumn female flight activity peak and male activity was best explained by photoperiod.

Seven‐metre tall suction traps are useful for determining when flight activity of A. glycines occurs within a region.
Development and validation of a model forecasting the phenology of European tarnished plant bug Lygus rugulipennis in the U.K
Authors: Xu Xiang‐Ming , Jay Chantelle N. , Fountain Michelle T. , Linka Judit , Fitzgerald Jean D.
Published: February 2014

The European tarnished plant bug Lygus rugulipennis has caused significant economic damage to strawberry production in the U.K. in recent years.

Laboratory experiments were conducted to study L. rugulipennis development under fluctuating low temperatures. The results indicated that L. rugulipennis can develop at an appreciable rate at 10 °C.

We have developed a model predicting the phenology of L. rugulipennis in the U.K. The model assumes that adults overwinter and uses temperature from the first day of a calendar year to simulate pest development. The model was validated against field observations of L. rugulipennis population dynamics monitored under both open‐field and protected conditions on weeds and strawberry plants. Predicted L. rugulipennis population patterns from the model agreed well with the observed data.

The L. rugulipennis model can be used in practice to enable growers to identify the timing of the first generation of L. rugulipennis adult dispersal into strawberry, or other crops, from weeds. The model will also assist growers with the timing of the deployment of pheromone traps and interpreting the importance of trap catches. This will allow growers to better time and target applications of insecticides against damaging life stages of the pest.
Effects of Hormonal Contraception on Antiretroviral Drug Metabolism, Pharmacokinetics and Pharmacodynamics
Authors: Thurman Andrea R. , Anderson Sharon , Doncel Gustavo F.
Published: February 2014

Among women, human immunodeficiency virus type 1 (HIV‐1) infection is most prevalent in those of reproductive age. These women are also at risk of unintended or mistimed pregnancies. Hormonal contraceptives (HCs) are one of the most commonly used methods of family planning worldwide. Therefore, concurrent use of HC among women on antiretroviral medications (ARVs) is increasingly common. ARVs are being investigated and have been approved for pre‐exposure prophylaxis (PrEP), and therefore, drug–drug interactions must also be considered in HIV‐1‐negative women who want to prevent both unintended pregnancy and HIV‐1 infection. This article will review four main interactions: (i) the effect of HCs on ARV pharmacokinetics (PK) and pharmacodynamics (PD) during therapy, (ii) the effect of ARVs on HC PK and PD, (iii) the role of drug transporters on drug–drug interactions, and (iv) ongoing research into the effect of HCs on pre‐exposure prophylaxis PK and PD.
Leptin into the ventrolateral medulla facilitates chemorespiratory response in leptin‐deficient (ob/ob) mice
Authors: Bassi M. , Furuya W. I. , Menani J. V. , Colombari D. S. A. , do Carmo J. M. , da Silva A. A. , Hall J. E. , Moreira T. S. , Wenker I. C. , Mulkey D. K. , Colombari E.
Published: February 2014

Aim

Leptin, an adipocyte‐derived hormone, is suggested to participate in the central control of breathing. We hypothesized that leptin may facilitate ventilatory responses to chemoreflex activation by acting on respiratory nuclei of the ventrolateral medulla. The baseline ventilation and the ventilatory responses to CO2 were evaluated before and after daily injections of leptin into the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) for 3 days in obese leptin‐deficient (ob/ob) mice.

Methods

Male ob/ob mice (40–45 g, n = 7 per group) received daily microinjections of vehicle or leptin (1 μg per 100 nL) for 3 days into the RTN/pFRG. Respiratory responses to CO2 were measured by whole‐body plethysmography.

Results

Unilateral microinjection of leptin into the RTN/pFRG in ob/ob mice increased baseline ventilation (VE) from 1447 ± 96 to 2405 ±174 mL min−1 kg−1 by increasing tidal volume (VT) from 6.4 ± 0.4 to 9.1 ± 0.8 mL kg−1 (P < 0.05). Leptin also enhanced ventilatory responses to 7% CO2 (Δ = 2172 ± 218 mL min−1 kg−1, vs. control: Δ = 1255 ± 105 mL min−1 kg−1), which was also due to increased VT (Δ = 4.71 ± 0.51 mL kg−1, vs. control: Δ = 2.27 ± 0.20 mL kg−1), without changes in respiratory frequency. Leptin treatment into the RTN/pFRG or into the surrounding areas decreased food intake (83 and 70%, respectively), without significantly changing body weight.

Conclusion

The present results suggest that leptin acting in the respiratory nuclei of the ventrolateral medulla improves baseline VE and VT and facilitates respiratory responses to hypercapnia in ob/ob mice.
Ex Vivo production of platelets from stem cells
Authors: Avanzi Mauro P. , Mitchell William Beau
Published: February 2014

Stem cell technology holds great promise for transfusion medicine, and generation of platelets from stem cells would be transformative. Platelet transfusions are life saving for millions of people and the clinical demand for platelets continues to increase: there is a real need to increase the supply of platelets. Accordingly, there is great interest in the potential of producing platelets from stem cells for clinical use. There has been initial success in ex vivo generation of platelets from stem cells using cord blood stem cells, embryonic stem cells and induced pluripotent stem cells. However, the platelet yields achieved by these strategies have not been sufficient for clinical purposes. This review provides updated information about the current strategies of ex vivo generation of platelets. Megakaryocytopoiesis and platelet generation, along with the importance of genetic determinants of these processes, are reviewed in the context of efforts to generate these products from stem cells. Current challenges and rate‐limiting steps in ex vivo platelet generation are discussed, together with strategies to overcome them. While much work remains, great progress has been made, moving ex vivo generation of platelets ever closer to the clinic.
PARADIGM SHIFT: A MEAN FIELD GAME APPROACH
Authors: Besancenot Damien , Dogguy Habib
Published: February 2014

This paper analyses the consequences of young researchers' scientific choice on the dynamics of sciences. We develop a simple two state mean field game model to analyse the competition between two paradigms based on Kuhn's theory of scientific revolution. The dynamics of the model are driven by the scientific choice of young researchers at the beginning of their career. Despite the possibility of multiple equilibria, the model exhibits at least one stable solution in which both para digms coexist. The occurrence of shocks on the parameters may induce the shift from one paradigm to the other. During this shift, researchers' choice is proved to be having a great impact on the evolution of sciences.
Reduced Vascular Endothelial Growth Factor and Capillary Density in the Occipital Cortex in Dementia with Lewy Bodies
Authors: Miners Scott , Moulding Hayley , de Silva Rohan , Love Seth
Published: February 2014

In dementia with Lewy bodies (DLB), blood flow tends to be reduced in the occipital cortex. We previously showed elevated activity of the endothelin and angiotensin pathways in Alzheimer's disease (AD). We have measured endothelin‐1 (ET‐1) level and angiotensin‐converting enzyme (ACE) activity in the occipital cortex in DLB and control brains. We also measured vascular endothelial growth factor (VEGF); factor VIII‐related antigen (FVIIIRA) to indicate microvessel density; myelin‐associated glycoprotein (MAG), a marker of ante‐mortem hypoperfusion; total α‐synuclein (α‐syn) and α‐synuclein phosphorylated at Ser129 (α‐syn‐p129). In contrast to findings in AD, ACE activity and ET‐1 level were unchanged in DLB compared with controls. VEGF and FVIIIRA levels were, however, significantly lower in DLB. VEGF correlated positively with MAG concentration (in keeping with a relationship between reduction in VEGF and hypoperfusion), and negatively with α‐syn and α‐syn‐p129 levels. Both α‐syn and α‐syn‐p129 levels increased in human SH‐SY5Y neuroblastoma cells after oxygen‐glucose deprivation (OGD), and VEGF level was reduced in SH‐SY5Y cells overexpressing α‐syn. Taken together, our findings suggest that reduced microvessel density rather than vasoconstriction is responsible for lower occipital blood flow in DLB, and that the loss of microvessels may result from VEGF deficiency, possible secondary to the accumulation of α‐syn.
Human papillomavirus and p53 mutations in head and neck squamous cell carcinoma among Japanese population
Authors: Maruyama Hiromi , Yasui Toshimichi , Ishikawa‐Fujiwara Tomoko , Morii Eiichi , Yamamoto Yoshifumi , Yoshii Tadashi , Takenaka Yukinori , Nakahara Susumu , Todo Takeshi , Hongyo Tadashi , Inohara Hidenori
Published: February 2014

We aimed to reveal the prevalence and pattern of human papillomavirus (HPV) infection and p53 mutations among Japanese head and neck squamous cell carcinoma (HNSCC) patients in relation to clinicopathological parameters. Human papillomavirus DNA and p53 mutations were examined in 493 HNSCCs and its subset of 283 HNSCCs. Oropharyngeal carcinoma was more frequently HPV‐positive than non‐oropharyngeal carcinoma (34.4% vs 3.6%, P < 0.001), and HPV16 accounted for 91.1% of HPV‐positive tumors. In oropharyngeal carcinoma, which showed an increasing trend of HPV prevalence over time (P < 0.001), HPV infection was inversely correlated with tobacco smoking, alcohol drinking, p53 mutations, and a disruptive mutation (P = 0.003, <0.001, <0.001, and <0.001, respectively). The prevalence of p53 mutations differed significantly between virus‐unrelated HNSCC and virus‐related HNSCC consisting of nasopharyngeal and HPV‐positive oropharyngeal carcinomas (48.3% vs 7.1%, P < 0.001). Although p53 mutations were associated with tobacco smoking and alcohol drinking, this association disappeared in virus‐unrelated HNSCC. A disruptive mutation was never found in virus‐related HNSCC, whereas it was independently associated with primary site, such as the oropharynx and hypopharynx (P = 0.01 and 0.03, respectively), in virus‐unrelated HNSCC. Moreover, in virus‐unrelated HNSCC, G:C to T:A transversions were more frequent in ever‐smokers than in never‐smokers (P = 0.04), whereas G:C to A:T transitions at CpG sites were less frequent in ever‐smokers than in never‐smokers (P = 0.04). In conclusion, HNSCC is etiologically classified into virus‐related and virus‐unrelated subgroups. In virus‐related HNSCC, p53 mutations are uncommon with the absence of a disruptive mutation, whereas in virus‐unrelated HNSCC, p53 mutations are common, and disruptive mutagenesis of p53 is related with oropharyngeal and hypopharyngeal carcinoma.
Retrieval of various aspirated foreign bodies by flexible cryoprobe: in vitro feasibility study
Authors: Fruchter Oren , Kramer Mordechai R.
Published: February 2014

Introduction

Retrieval of aspirated foreign bodies (FB) by flexible bronchoscopy is challenging. Many types of ancillary equipment, including forceps, grasping claws, snares, balloon‐tipped catheters and magnets, have been developed to allow FB extraction using flexible bronchoscopes. The ability to remove a FB by flexible cryoprobe (cryoextraction) depends on the cryoadhesive properties of the retrieved object, which in turn depends on its physical properties.

Objectives

Our aim was to explore ex vivo on a lung model the cryoadhesive properties of various commonly aspirated objects.

Methods

The tested FB compromised of nine organic and nine inorganic commonly aspirated objects. An attempt was made to retrieve each object from a lung model by flexible cryoprobe at 5 and 10 s application time and following rinsing by normal saline.

Results

Whereas most organic objects (for example chicken and fish bones) were retrievable by cryoprobe, most inorganic objects (for example safety pin and paper clip) are not retrievable by cryoadhesion. On the other hand, several inorganic objects (for example dental cup) despite their low water content were cryoadhesive.

Conclusion

FB retrieval by cryoprobe is feasible for many organic and inorganic aspirated objects. However, the cryoadhesive properties of most inorganic FB and several organic objects is unpredictable, hence, if the nature of the FB is known, an identical object should be used to practice the technique of retrieval in vitro, prior to attempting to perform the procedure in the patient.
The role ofTc‐99mDTPAaerosol scintigraphy in the differential diagnosis ofCOPDand asthma
Authors: Karacavus Seyhan , Intepe Yavuz S.
Published: February 2014

Objective

Chronic obstructive lung disease (COPD) and asthma are characterized as similar to each other in causing airway obstruction and being an inflammatory process. The purpose of this study was to investigate whether technetium‐99m diethylenetriaminepentaacetic acid (99mTc‐DTPA) aerosol scintigraphy could be used in the differential diagnosis of asthma andCOPD.

Methods

Eighty‐four patients (male/female: 32/52; mean age 50.2 ± 12.7 years) with obstructive lung disease and 30 healthy volunteers as the control group were enrolled in the study. The patients were divided into two groups asCOPDand asthma and also smoking subgroups. Alveolar clearance study was performed using a radiolabeled aerosol of99mTc‐DTPA. Mucociliary clearance was evaluated withT½, cap value and penetration index parameters. All patient underwent pulmonary function tests and Forced expiratory volume (FEV1), forced vital capacity (FVC) andFEV1/FVCparameters were obtained.

Results

The mean ofT½values of99mTc‐DTPAaerosol andFEV1/FVCvalue among spirometric tests of the nonsmokingCOPDpatients were significantly lower than nonsmoking asthma patients (46.1 ± 14.3, 62.3 ± 18.7,P = 0.02; 65.2 ± 10.8, 81.4 ± 16.5,P = 0.04, respectively). The cap value was significantly higher in nonsmokingCOPDpatients (1.21 ± 0.49, 0.76 ± 0.22,P = 0.03). While there were no statistically and significantly different between control and asthmatic groups at the scintigraphic parameters and spirometric parameters, the mean ofT½values, cap value and spirometric parameters were statistically different between control andCOPDgroups (P < 0.05).

Conclusion

We showed that assessment of mucociliary permeability with99mTc‐DTPAaerosol scintigraphy was a useful, easy to apply and a noninvasive technique to use in the differential diagnosis of nonsmokerCOPDand asthma.
Artemisia dracunculus L. extract ameliorates insulin sensitivity by attenuating inflammatory signalling in human skeletal muscle culture
Authors: Vandanmagsar B. , Haynie K. R. , Wicks S. E. , Bermudez E. M. , Mendoza T. M. , Ribnicky D. , Cefalu W. T. , Mynatt R. L.
Published: February 2014

Aims

Bioactives of Artemisia dracunculus L. (termed PMI 5011) have been shown to improve insulin action by increasing insulin signalling in skeletal muscle. However, it was not known if PMI 5011's effects are retained during an inflammatory condition. We examined the attenuation of insulin action and whether PMI 5011 enhances insulin signalling in the inflammatory environment with elevated cytokines.

Methods

Muscle cell cultures derived from lean, overweight and diabetic‐obese subjects were used. Expression of pro‐inflammatory genes and inflammatory response of human myotubes were evaluated by real‐time polymerase chain reaction (RT‐PCR). Insulin signalling and activation of inflammatory pathways in human myotubes were evaluated by multiplex protein assays.

Results

We found increased gene expression of monocyte chemoattractant protein 1 (MCP1) and TNFα (tumour necrosis factor alpha), and basal activity of the NFkB (nuclear factor kappa‐light‐chain‐enhancer of activated B cells) pathway in myotubes derived from diabetic‐obese subjects as compared with myotubes derived from normal‐lean subjects. In line with this, basal Akt phosphorylation (Ser473) was significantly higher, while insulin‐stimulated phosphorylation of Akt (Ser473) was lower in myotubes from normal‐overweight and diabetic‐obese subjects compared with normal‐lean subjects. PMI 5011 treatment reduced basal phosphorylation of Akt and enhanced insulin‐stimulated phosphorylation of Akt in the presence of cytokines in human myotubes. PMI 5011 treatment led to an inhibition of cytokine‐induced activation of inflammatory signalling pathways such as Erk1/2 and IkBα (nuclear factor of kappa light polypeptide gene enhancer in B‐cells inhibitor, alpha)‐NFkB and moreover, NFkB target gene expression, possibly by preventing further propagation of the inflammatory response within muscle tissue.

Conclusions

PMI 5011 improved insulin sensitivity in diabetic‐obese myotubes to the level of normal‐lean myotubes despite the presence of pro‐inflammatory cytokines.
Lixisenatide resensitizes the insulin‐secretory response to intravenous glucose challenge in people with type 2 diabetes – a study in both people with type 2 diabetes and healthy subjects
Authors: Becker R. H. A. , Stechl J. , Msihid J. , Kapitza C.
Published: February 2014

Aims

Glucagon‐like peptide‐1 (GLP‐1) receptor agonists improve blood glucose control by enhancing glucose‐sensitive insulin release, delaying gastric emptying and reducing postprandial glucagon secretion. The studies reported here investigated the insulin response to an intravenous (iv) glucose challenge after injection of lixisenatide (LIXI) 20 µg or placebo.

Methods

Two single‐centre, double‐blind, randomized, placebo‐controlled, single‐dose, crossover studies were performed in healthy subjects (HS) and people with type 2 diabetes mellitus (T2DM). Participants received subcutaneous LIXI or placebo 2 h before an iv glucose challenge. Study endpoints included first‐ and second‐phase insulin response, insulin concentration (INS), glucagon response and glucose disposal rate (Kglucose). LIXI exposure was measured over 12 h.

Results

LIXI 20 µg reached maximum concentration after 2 h and resensitized first‐phase insulin secretion by 2.8‐fold in T2DM to rates comparable with those in HS on placebo, and raised second‐phase insulin secretion by 1.6‐fold in T2DM. INS rose correspondingly and glucose disposal was accelerated by 1.8‐fold in T2DM. First‐phase insulin secretion and glucose disposal were also augmented by LIXI in HS, whereas second‐phase insulin secretion reduced blood glucose concentrations to below fasting levels and then ceased, accompanied by a rapid, short‐lasting rise in glucagon. Otherwise, suppression of glucagon release subsequent to augmentation of insulin release was unaffected in T2DM and in HS.

Conclusions

LIXI resensitized the insulin response to an iv glucose challenge in people with T2DM, thereby accelerating glucose disposal to nearly physiological intensity, and did not impair counter‐regulation to low glucose levels by glucagon.