bluuebunny/crossref_metadata_2025 huggingface dataset:
Negative effects of mass tourism on high mountain fauna: the case of the Tatra chamoisRupicapra rupicapra tatrica
Authors: Pęksa Łukasz , Ciach Michał
Published: August 2014

Until recently animals inhabiting mountain areas were relatively free from disturbance by people but they are now coming under increasing pressure. Tourism, especially that involving large numbers of people, is having an ever more detrimental effect on the natural resources of high mountains, even in protected areas. We analyse the effect of tourist pressure on the population of the Tatra chamoisRupicapra rupicapra tatrica, which inhabits the strictly protected high-altitude habitats of the Tatra mountains (Carpathians, Poland). The Kasprowy Wierch cable car system, in operation since 1936, was modernized in 2007; as a consequence 50% more people can now be carried into the chamois’ habitat. The effect of this sudden increase in tourist pressure has been to reduce the size of herds (3.9 vs 5.3 individuals) and to increase the distance between the animals and the cable car station (1,664.0 vs 693.0 m), the cable car infrastructure (1,415.0 vs 467.8 m) and adjacent ski-lifts and ski pistes (1,214.2 vs 494.3 m). The distance to the marked hiking trails has not changed, however. Following the modernization of the cable cars, larger herds of chamois have been seen at greater distances from the tourist infrastructure. Our results indicate the adverse impact of this mass tourism. Human activities in high-mountain ecosystems need to have due consideration for the requirements of wild species, and the number of visitors needs to be controlled.
What we (don't) know about the effects of habitat loss and fragmentation on felids
Authors: Zanin Marina , Palomares Francisco , Brito Daniel
Published: August 2014

Felid species have intrinsic ecological traits that make them particularly susceptible to the threats of habitat loss and fragmentation. We collate current knowledge of the effects of habitat loss and fragmentation on felids, describing trends, investigating the allocation of research effort and identifying knowledge gaps. We searched the scientific literature and categorized articles according to conceptual and methodological approaches. We reviewed 162 articles and observed that scientific knowledge is unevenly distributed among topics and species. Habitat suitability and patch–landscape configuration are the most studied topics. The allocation of research effort is unrelated to variables that describe conservation priorities, such as threat status and habitat availability within a species’ range, but it is related to body size, suggesting that charismatic attributes influence the choice of target species. Countries with less research effort are also those with less economic development, and thus North America and Europe are the centres of knowledge generation of reviewed studies. The responses of sixteen felid species to habitat loss and fragmentation remain unknown. Of these the Andean mountain catLeopardus jacobita, the Bornean bay catPardofelis badia, the flat-headed catPrionailurus planicepsand the fishing catPrionailurus viverrinusmost urgently require research because they are threatened with extinction. We recommend the use of theoretical approaches, through modelling exercises, as a first step to address the lack of information about the effects of habitat loss and fragmentation on felids, especially for those species for which there are large knowledge gaps.
Diphenyl diselenide and sodium selenite associated with chemotherapy in experimental toxoplasmosis: influence on oxidant/antioxidant biomarkers and cytokine modulation
Authors: BARBOSA CLEBER F. , TONIN ALEXANDRE A. , DA SILVA ALEKSANDRO S. , DE AZEVEDO MARIA I. , MONTEIRO DANIELI U. , WACZUK EMILY P. , DUARTE THIAGO , HERMES CARINE , CAMILLO GIOVANA , VOGEL FERNANDA F. , FACCIO LUCIANA , TONIN PAULA T. , WOLKMER PATRICIA , LEAL MARTA R. , DUARTE MARTA M. M. F. , MORESCO RAFAEL N. , LOPES SONIA T. A. , DE LA RUE MARIO L.
Published: August 2014

The aim of this study was to assess the effect of sulfamethoxazole/trimethoprim (ST) supplemented with diphenyl diselenide and sodium selenite in experimental toxoplasmosis, on oxidant/antioxidant biomarkers and cytokine levels. Eighty-four BALB/c mice were divided in seven groups: group A (negative control), and groups B to G (infected). Blood and liver samples were collected on days 4 and 20 post infection (p.i.). Levels of thiobarbituric acid (TBA) reactive substances and advanced oxidation protein products (AOPP) were assessed in liver samples. Both biomarkers were significantly increased in infected groups on day 4 p.i., while they were reduced on day 20 p.i., compared with group A. Glutathione reductase (GR) activity significantly (P<0·01) increased on day 4 p.i., in group G, compared with group A. INF-γwas significantly increased (P<0·001) in both periods, day 4 (groups B, C, F and G) and 20 p.i. (groups C, F and G). IL-10 significantly reduced (P<0·001) on day 4 p.i. in group B; however, in the same period, it was increased (P<0·001) in groups C and G, compared with group A. On day 20 p.i., IL-10 increased (P<0·001) in groups F and G. Therefore, our results highlighted that these forms of selenium, associated with the chemotherapy, were able to reduce lipid peroxidation and protein oxidation, providing a beneficial immunological balance between the production of pro- and anti-inflammatory cytokines.
Expression of heat shock protein 47, transforming growth factor-beta 1, and connective tissue growth factor in liver tissue of patients with Schistosoma japonicum-induced hepatic fibrosis
Authors: LI LAN , WU TING , HUANG JIAQUAN , MA KE , XU LEI , WANG HONGWU , FAN XIANGXUE , TAO RAN , AI GUO , NING QIN
Published: August 2014

To detect the expression of pro-fibrotic molecules, such as heat shock protein 47 (Hsp47), transforming growth factor-beta 1 (TGF-β1) and connective tissue growth factor (CTGF) in liver specimens, and analyse their correlations with the progression of schistosomal hepatic fibrosis, liver biopsy was performed in 42 chronic schistosomiasis (CS) patients, 16 chronic hepatitis B (CHB) patients and five healthy individuals (HI). Immunohistochemistry (IHC) analyses displayed that the expression of Hsp47, TGF-β1 and CTGF was increased in CS and CHB patients compared with HI. Using real-time PCR, the mRNA levels of Hsp47, TGF-β1 and CTGF were higher in CS patients compared with HI. In CS patients, the mRNA levels of these genes were correlated with the stage of fibrosis, and TGF-β1 mRNA expression was associated with the grade of inflammation. Additional analyses indicated that the mRNA levels of Hsp47 and CTGF were highly correlated with liver stiffness value and spleen thickness diameter, both of which represented the severity of fibrosis. In conclusion, the three molecules are involved in the pathogenesis of hepatic fibrosis infected by Schistosoma japonicum. TGF-β1 participates not only in the inflammatory process, but also in the fibrotic process in which Hsp47 and CTGF probably play a key role.
Gender–age interaction in incidence rates of childhood emotional disorders
Authors: Wesselhoeft R. , Pedersen C. B. , Mortensen P. B. , Mors O. , Bilenberg N.
Published: August 2014

Background

The post-pubertal association of female gender with emotional disorder is a robust finding. However, studies exploring the association of gender and emotional disorders before puberty are few and present diverging results. The aim of this study was to present gender-specific incidence rates of emotional disorders throughout childhood.

Method

This is a population-based cohort study of 907 806 Danish 3- to 18-year-olds. The outcome was assignment of an emotional disorder diagnosis based on in-patient and out-patient data from The Danish Psychiatric Central Register. Outcome measures were incidence rates and cumulative incidences for unipolar depressive disorder (ICD-10: F32–F33), anxiety disorders (ICD-10: F40–F42), and emotional disorders with onset specific to childhood (ICD-10: F93).

Results

Pre-pubertal incidence rates for depressive and anxiety disorders were higher for boys than girls. At age 12 years the pattern reversed. The cumulative incidence for any emotional disorder (F32–F33, F40–F42, F93) on the 11th birthday was 0.52% (95% CI 0.50–0.55) for boys and 0.31% (95% CI 0.29–0.33) for girls. On the 19th birthday cumulative incidence was 2.33% (95% CI 2.24–2.43) for boys and 3.77% (95% CI 3.64–3.90) for girls. The pre-pubertal male preponderance was also significant for depressive disorders (F32–F33, p = 0.00144) and anxiety disorders (F40–F42, F93, p < 0.00001) separately.

Conclusions

Emotional disorders seem to display a male preponderance before the age of 12 years and a female preponderance thereafter. Studies exploring this gender–age interaction are needed. Still, the results question the general assumption that females throughout the lifespan are more at risk for emotional disorders than males.
Sensation Seeking as It Relates to Burnout Among Emergency Medical Personnel: A Texas Study
Authors: Chng Chwee Lye , Eaddy Starr
Published: August 2014

Introduction:

Burnout among emergency medical personnel (emergency medical personne) is suspected, but largely unsupported in the literature. An investigation of the phenomenon of burnout and factors contributing to its existence are essential steps in designingeffective interventions.

Research Questions:

Three research questions were proposed: 1) Are EMP sensation seekers as measured by Arnett's Inventory of Sensation Seeking? 2) Are EMP burnt out as measured by Revicki's Work-Related Strain Inventory? 3) Is there a relationship between sensation seeking and burnout among EMP?

Methods:

Emergency medical personnel attending a statewide conference in Texas, USA in late 1996 completed 425 survey instruments measuring sensation seeking and burnout as well as demographic items. Survey instruments were included in each registrant's conference package. Completed surveys were deposited anonymously in labeled receptacles throughout the statewide conference site. Data collection ceased at the end of the conference.

Results:

Emergency Medical Personne had significantly higher sensation–seeking total and intensity sub–scale scores than the general public. Full–time employees reported more sensation–seeking than volunteers or part–time employees. The younger the Emergency Medical Personne, the greater were their reported sensation seeking tendencies. Emergency Medical Personne reported more burnout in 1996 than in 1991. The older the Emergency Medical Personne, the lower was the reported level of burnout. Emergency Medical Personne who sought counseling for a work–related event reported more burnout than those who did not. Paid full–time Emergency Medical Personne reported higher burnout than did volunteers. There was a weak but positive correlation between sensation seeking and burnout, suggesting that these two dimensions may be unrelated.

Conclusion:

The field of emergency medical services attracts sensation seekers, and Emergency Medical Personne today report more burnout than their counterparts did in 1991. Although Emergency Medical Personne appear to be high in sensation seeking, this dimension alone does not protect them from the effects of burnout.
Evaluation of a Belly Board immobilisation device for rectal cancer patients receiving pre-operative chemoradiation
Authors: Gaya Andrew , Brulinski Patryk , Morris Stephen L. , Ball Kim A. , Greener Anthony G. , Corcoran Sue , Henrys Anthony , Landau David B. , Mikhaeel George , Leslie Martin D. , Winship Anna Z.
Published: August 2014

Purpose

To evaluate the efficacy of a Belly Board immobilisation device for rectal cancer patients.

Materials and methods

A randomised trial in patients receiving neo-adjuvant chemoradiation for rectal carcinoma was established. Patients were treated, prone with control arm, according to standard departmental protocol and experimental arm with the use of a Belly Board. All treatments were planned using a three-field technique. The primary endpoints were reproducibility and irradiated small bowel volume. Questionnaires were used to assess secondary endpoints of patient comfort, ease of set-up and acute toxicities.

Results

Pre-planned interim analysis was performed after recruiting 30 patients. In all, 348 portal images were analysed retrospectively. Around 8 out of 12 parameters measuring set-up reproducibility were in favour of the Belly Board arm. Random error in the anterior–posterior direction was improved and statistically significant in the experimental arm (95% CI; p≤0·05). Small bowel V15 was significantly lower in the Belly Board position (mean V15=14·5%) compared with the standard position (mean V15=21·4%), paired t-test 95% CI; p=0·035. Also, patients’ comfort satisfaction was greater in the Belly Board arm.

Conclusions

Set-up reproducibility, small bowel V15, patient comfort and satisfaction were all significantly improved by the use of the Belly Board.
EXTENSIONS ENTRE SÉRIES PRINCIPALES -ADIQUES ET MODULO DE
Authors: Hauseux Julien
Published: August 2014

Soit$G$un groupe réductif connexe déployé sur une extension finie$F$de$\mathbb{Q}_{p}$. Nous déterminons les extensions entre séries principales continues unitaires$p$-adiques et lisses modulo$p$de$G(F)$dans le cas générique. Pour cela, nous calculons le delta-foncteur$\text{H}^{\bullet }\text{Ord}_{B(F)}$des parties ordinaires dérivées d’Emerton relatif à un sous-groupe de Borel sur certaines représentations induites de$G(F)$en utilisant une filtration de Bruhat. Ces extensions interviennent dans le programme de Langlands$p$-adique et modulo $p$.
RasGRP3 limits Toll-like receptor-triggered inflammatory response in macrophages by activating Rap1 small GTPase
Authors: Tang Songqing , Chen Taoyong , Yu Zhou , Zhu Xuhui , Yang Mingjin , Xie Bin , Li Nan , Cao Xuetao , Wang Jianli
Published: August 2014

Host immune cells can detect and destruct invading pathogens via pattern-recognition receptors. Small Rap GTPases act as conserved molecular switches coupling extracellular signals to various cellular responses, but their roles as regulators in Toll-like receptor (TLR) signalling have not been fully elucidated. Here we report that Ras guanine nucleotide-releasing protein 3 (RasGRP3), a guanine nucleotide-exchange factor activating Ras and Rap1, limits production of proinflammatory cytokines (especially IL-6) in macrophages by activating Rap1 on activation by low levels of TLR agonists. We demonstrate that RasGRP3, a dominant member of RasGRPs in macrophages, impairs TLR3/4/9-induced IL-6 production and relieves dextrane sulphate sodium-induced colitis and collagen-induced arthritis. In RasGRP3-deficient RAW264.7 cells obtained by CRISPR-Cas9 genome editing, TLR3/4/9-induced activation of Rap1 was inhibited while ERK1/2 activation was enhanced. Our study suggests that RasGRP3 limits inflammatory response by activating Rap1 on low-intensity pathogen infection, setting a threshold for preventing excessive inflammatory response.
Pushing the detection limit of infrared spectroscopy for structural analysis of dilute protein samples
Authors: Baldassarre Maurizio , Barth Andreas
Published: August 2014

Optical filters dramatically reduce the noise of protein infrared spectra and allow for a more accurate structural analysis of dilute protein samples.
Simultaneous analysis of coumarin derivatives in extracts of Radix Angelicae pubescentis (Duhuo) by HPLC-DAD-ESI-MSn technique
Authors: Wang Bin , Liu Xianhua , Zhou An , Meng Mei , Li Qinglin
Published: August 2014

Radix Angelicae pubescentis (Duhuo) is a traditional Chinese herbal medicine (TCM) used for the treatment of rheumatic diseases.
Self-assembly of a tripeptide into a functional coating that resists fouling
Authors: Maity Sibaprasad , Nir Sivan , Zada Tal , Reches Meital
Published: August 2014

A short peptide (tripeptide) self-assembles into a supramolecular functional coating with antifouling activity. This coating can be useful in applications where the adsorption of proteins, bacteria and other organisms should be avoided.
A multi-ligation strategy for the synthesis of heterofunctionalized glycosylated scaffolds
Authors: Thomas Baptiste , Fiore Michele , Daskhan Gour Chand , Spinelli Nicolas , Renaudet Olivier
Published: August 2014

Well-defined heterofunctionalized glycosylated scaffolds with unprecedented molecular combinations have been prepared using up to five different bioorthogonal ligations.
Effect of metal doping, doped structure, and annealing under argon on the properties of 30 nm thick ultrathin hematite photoanodes
Authors: Kim Tae-Ho , Kim Hyun Sung , Hwang In-Chul , Yoon Kyung Byung
Published: August 2014

The doping of the whole hematite layer with W (9.4%) and the additional doping of the bottom half of the W-doped hematite layer with Sn (8.6%), and the subsequent annealing under argon at 600 °C give rise to a large increase in current density by ∼8 times at 1.23 V vs. RHE, under 1 sun.
Partial alkali-metal ion extraction from K0.8(Li0.27Ti1.73)O4 using PTFE as an extraction reagent
Authors: Ozawa Tadashi C. , Sasaki Takayoshi
Published: August 2014

53% of interlayer K+ and 10% of intralayer Li+ were extracted from K0.8(Li0.27Ti1.73)O4 by the reaction with PTFE.
Theoretical insights into the reductive metabolism of CCl4 by cytochrome P450 enzymes and the CCl4-dependent suicidal inactivation of P450
Authors: Li Xiao-Xi , Zheng Qing-Chuan , Wang Yong , Zhang Hong-Xing
Published: August 2014

The one-electron reduction product, ˙CCl3, irreversibly inactivates P450 via covalently binding to the meso-carbon, whereas the two successive one-electron reductions product, :CCl2, reversibly inhibits P450 by coordinating to iron.
Living polymerization of arylisocyanide initiated by the phenylethynyl palladium(ii) complex
Authors: Xue Ya-Xin , Chen Jia-Li , Jiang Zhi-Qiang , Yu Zhipeng , Liu Na , Yin Jun , Zhu Yuan-Yuan , Wu Zong-Quan
Published: August 2014

An air-stable phenylethynyl palladium(ii) complex was unexpectedly found to initiate the living polymerization of phenyl isocyanide.
A green protocol for the Pd catalyzed ligand free homocoupling reaction of arylboronic acids under ambient conditions
Authors: Dwivedi Seema , Bardhan Soumik , Ghosh Prasanjit , Das Sajal
Published: August 2014

A simple, competent, green pathway has been developed for the Pd catalyzed ligand free homocoupling reaction of arylboronic acids in water under ambient conditions.
Multifunctional iron oxide/silk-fibroin (Fe3O4–SF) composite microspheres for the delivery of cancer therapeutics
Authors: Zhang Haiyun , Ma Xilan , Cao Chuanbao , Wang Meina , Zhu Youqi
Published: August 2014

In this article, we report novel multifunctional iron oxide/silk-fibroin (Fe3O4–SF) microspheres synthesized by simple salting out process.
Pyrite transformation and sulfur dioxide release during calcination of coal gangue
Authors: Zhang Yingyi , Ge Xinlei , Nakano Jinichiro , Liu Lili , Wang Xidong , Zhang Zuotai
Published: August 2014

The SO2 emission behavior of coal gangue during calcination was systematically investigated.
Chemical modification of polysiloxanes with polar pendant groups by co-hydrosilylation
Authors: Racles Carmen , Alexandru Mihaela , Bele Adrian , Musteata Valentina E. , Cazacu Maria , Opris Dorina M.
Published: August 2014

Polysiloxanes were modified by (co-)hydrosilylation with γ-cyanopropyl and hexyl groups, to finely tune their composition and properties, especially dielectric permittivity, as a way towards active components in dielectric elastomer transducers. Un-modified Si–H groups can be further used to obtain cross-linked thin films.
A facile acidic choline chloride–p-TSA DES-catalysed dehydration of fructose to 5-hydroxymethylfurfural
Authors: Assanosi Amhamed A. , Farah Mohamed M. , Wood Joseph. , Al-Duri Bushra
Published: August 2014

The conversion of lignocellulosic biomass to biofuel precursors has recently been a focus of intensive research due to the essential role of biofuels as transport fuels in the future.
Function-oriented investigations of a peptide-based catalyst that mediates enantioselective allylic alcohol epoxidation.
Authors: Abascal Nadia C. , Lichtor Phillip A. , Giuliano Michael W. , Miller Scott J.
Published: August 2014

Experimentally derived analysis of selectivity of a peptide catalyst through study of substrate scope, kinetics, catalyst analogues, and NMR data.
Electrostatic control of regioselectivity via ion pairing in a Au(i)-catalyzed rearrangement
Authors: Lau Vivian M. , Gorin Craig F. , Kanan Matthew W.
Published: August 2014

Ion pairing controls regioselectivity in a Au(i)-catalyzed rearrangement by favoring the more polar product-determining transition state.
Unexplained transport resistances for low-loaded fuel-cell catalyst layers
Authors: Weber Adam Z. , Kusoglu Ahmet
Published: August 2014

Mass-transport limitations due to the resistances caused by the ionomer thin-film surrounding the catalyst sites must be mitigated to achieve the desired performance with low catalyst loadings, a key for the commercialization of polymer-electrolyte fuel cells.
An introduction to systems toxicology
Authors: Plant Nick J.
Published: August 2014

Systems toxicology combines novel and historical experimental data to generate increasingly complex models of the biological response to chemical exposure.
Translation of off-target effects: prediction of ADRs by integrated experimental and computational approach
Authors: Urban Laszlo , Maciejewski Mateusz , Lounkine Eugen , Whitebread Steven , Jenkins Jeremy L. , Hamon Jacques , Fekete Alexander , Muller Patrick Y.
Published: August 2014

Adverse drug reactions (ADRs) are associated with most drugs, often discovered late in drug development and sometimes only during extended course of clinical use.
Female puberty acceleration by male odour in mice: neural pathway and behavioural consequences
Authors: Jouhanneau Mélanie , Szymanski Laura A. , Keller Matthieu
Published: August 2014

In female mice, exposure to male chemosignals results in early puberty onset characterized by advanced vaginal opening and higher uterine weight. Evidence suggests that the male chemosignals responsible for acceleration of female puberty are androgen-dependent, but not all of the compounds that contribute to puberty acceleration have been identified. The male chemosignals are primarily detected and processed by the vomeronasal system including the vomeronasal organ, the accessory olfactory bulb and the medial amygdala. By contrast, the mechanism by which this olfactory information is integrated in the hypothalamus is poorly understood. In this context, the recent identification of the neuropeptide kisspeptin as a gatekeeper of puberty onset may provide a good candidate neuropeptide system for the transmission of chemosensory information to the gonadotrope axis.
The fission yeast Schizosaccharomyces pombe as a model to understand how peroxiredoxins influence cell responses to hydrogen peroxide
Authors: Veal Elizabeth A. , Tomalin Lewis E. , Morgan Brian A. , Day Alison M.
Published: August 2014

As a more selectively reactive oxygen species, H2O2 (hydrogen peroxide) has been co-opted as a signalling molecule, but high levels can still lead to lethal amounts of cell damage. 2-Cys Prxs (peroxiredoxins) are ubiquitous thioredoxin peroxidases which utilize reversibly oxidized catalytic cysteine residues to reduce peroxides. As such, Prxs potentially make an important contribution to the repertoire of cell defences against oxidative damage. Although the abundance of eukaryotic 2-Cys Prxs suggests an important role in maintaining cell redox, the surprising sensitivity of their thioredoxin peroxidase activity to inactivation by H2O2 has raised questions as to their role as an oxidative stress defence. Indeed, work in model yeast has led the way in revealing that Prxs do much more than simply remove peroxides and have even uncovered circumstances where their thioredoxin peroxidase activity is detrimental. In the present paper, we focus on what we have learned from studies in the fission yeast Schizosaccharomyces pombe about the different roles of 2-Cys Prxs in responses to H2O2 and discuss the general implications of these findings for other systems.
RNA granules and cytoskeletal links
Authors: Rajgor Dipen , Shanahan Catherine M.
Published: August 2014

In eukaryotic cells, non-translating mRNAs can accumulate into cytoplasmic mRNP (messenger ribonucleoprotein) granules such as P-bodies (processing bodies) and SGs (stress granules). P-bodies contain the mRNA decay and translational repression machineries and are ubiquitously expressed in mammalian cells and lower eukaryote species including Saccharomyces cerevisiae, Drosophila melanogaster and Caenorhabditis elegans. In contrast, SGs are only detected during cellular stress when translation is inhibited and form from aggregates of stalled pre-initiation complexes. SGs and P-bodies are related to NGs (neuronal granules), which are essential in the localization and control of mRNAs in neurons. Importantly, RNA granules are linked to the cytoskeleton, which plays an important role in mediating many of their dynamic properties. In the present review, we discuss how P-bodies, SGs and NGs are linked to cytoskeletal networks and the importance of these linkages in maintaining localization of their RNA cargoes.
PI3K/Akt-mediated regulation of p53 in cancer
Authors: Abraham Aswin G. , O’Neill Eric
Published: August 2014

Mutations activating the PI3K (phosphoinositide 3-kinase)/Akt signalling pathway and inactivating the TP53 tumour-suppressor gene are common mechanisms that cancer cells require to proliferate and escape pre-programmed cell death. In a well-described mechanism, Akt mediates negative control of p53 levels through enhancing MDM2 (murine double minute 2)-mediated targeting of p53 for degradation. Accumulating evidence is beginning to suggest that, in certain circumstances, PTEN (phosphatase and tensin homologue deleted on chromosome 10)/PI3K/Akt also promotes p53 translation and protein stability, suggesting that additional mechanisms may be involved in the Akt-mediated regulation of p53 in tumours. In the present article, we discuss these aspects in the light of clinical PI3K/Akt inhibitors, where information regarding the effect on p53 activity will be a crucial factor that will undoubtedly influence therapeutic efficacy.
Chemical biology tools to study pantetheinases of the vanin family
Authors: Schalkwijk Joost , Jansen Patrick
Published: August 2014

VNNs (vanins) are pantetheinases that hydrolyse pantetheine to pantothenic acid and cysteamine. Studies with Vnn1-knockout mice have indicated a role of VNN-1 in inflammation and stress responses. VNN-1 is highly expressed in liver and is under transcriptional control of PPAR (peroxisome-proliferator-activated receptor)-α and nutritional status, suggesting a role in energy metabolism. Recently, the specific substrates and inhibitors of VNNs were obtained as tools to study VNN biology and to investigate whether VNNs are potential drug targets. Oral administration of RR6, a pantothenone with nanomolar anti-VNN potency, completely inhibited plasma VNN activity in rats and showed favourable pharmacokinetics. Prolonged RR6 administration caused alterations of hepatic and plasma lipid concentrations upon fasting. VNN inhibitors were found to protect pantothenamides (pantetheine analogues with antibiotic activity) against breakdown by plasma VNN, thereby preserving their antibiotic activity. Combination of pantothenamides with a VNN inhibitor showed a strong activity against Staphylococcus aureus and Staphylococcus pneumoniae when assayed in the presence of 10% serum. Recent studies have reported plasma stable pantothenamides that were active against the malaria parasite Plasmodium falciparum. We conclude that VNN inhibitors and pantothenate derivatives that target enzymes in the CoA (coenzyme A) biosynthetic pathway may have potential use as novel drugs in infection, inflammation and metabolism.
Manganese superoxide dismutase in carcinogenesis: friend or foe?
Authors: Konzack Anja , Kietzmann Thomas
Published: August 2014

Superoxide and its derived ROS (reactive oxygen species) have been considered for a long time to be generated as toxic by-products of metabolic events. Although ROS generated in low amounts are able to act as signalling molecules, ROS appear to also play a major role in aging and in the pathogenesis of diseases such as inflammation, diabetes and cancer. Since superoxide formation, in particular in mitochondria, is often considered to be an initial step in the pathogenesis of these diseases, improper function of the MnSOD (mitochondrial superoxide dismutase; SOD2) may be critical for tissue homoeostasis. However, the underlying regulatory mechanisms appear to be multiple and this article summarizes current aspects by which MnSOD can regulate carcinogenesis under various conditions.
Application of redox proteomics to skeletal muscle aging and exercise
Authors: McDonagh Brian , Sakellariou Giorgos K. , Jackson Malcolm J.
Published: August 2014

Skeletal muscle represents a physiologically relevant model for the application of redox proteomic techniques to dissect its response to exercise and aging. Contracting skeletal muscles generate ROS (reactive oxygen species) and RNS (reactive nitrogen species) necessary for the regulation of many proteins involved in excitation–contraction coupling. The magnitude and species of ROS/RNS generated by contracting muscles will have downstream effects on specific protein targets and cellular redox signalling. Redox modifications on specific proteins are essential for the adaptive response to exercise and skeletal muscle can develop a dysregulated redox response during aging. In the present article, we discuss how redox proteomics can be applied to identify and quantify the reversible modifications on susceptible cysteine residues within those redox-sensitive proteins, and the integration of oxidative and non-oxidative protein modifications in relation to the functional proteome.
Yeast mRNA localization: protein asymmetry, organelle localization and response to stress
Authors: Pizzinga Mariavittoria , Ashe Mark P.
Published: August 2014

The localization of mRNA forms a key facet of the post-transcriptional control of gene expression and recent evidence suggests that it may be considerably more widespread than previously anticipated. For example, defined mRNA-containing granules can be associated with translational repression or activation. Furthermore, mRNA P-bodies (processing bodies) harbour much of the mRNA decay machinery and stress granules are thought to play a role in mRNA storage. In the present review, we explore the process of mRNA localization in the yeast Saccharomyces cerevisiae, examining connections between organellar mRNA localization and the response to stress. We also review recent data suggesting that even where there is a global relocalization of mRNA, the specificity and kinetics of this process can be regulated.
Acute kidney injury: a paradigm for miRNA regulation of the cell cycle
Authors: Khalid Usman , Bowen Timothy , Fraser Donald J. , Jenkins Robert H.
Published: August 2014

miRNAs are small, endogenous, post-transcriptional regulators of gene expression. AKI (acute kidney injury) of various aetiologies, including trauma, sepsis and IRI (ischaemia/reperfusion injury) in the context of kidney transplantation, or drug toxicity, has a high morbidity and mortality rate and presents a significant burden to health services worldwide. AKI primarily affects the renal cortex, in particular PTCs (proximal tubular epithelial cells). Current research demonstrates causality between G2/M cell cycle arrest of PTCs and AKI. Recent findings from our laboratory and others presented in this review implicate miRNA regulation of the cell cycle in the pathology of AKI.
Intermolecular disulfide-dependent redox signalling
Authors: Putker Marrit , Vos Harmjan R. , Dansen Tobias B.
Published: August 2014

Until recently, ROS (reactive oxygen species) were often seen as merely damaging agents. However, small, but significant, amounts of hydrogen peroxide (H2O2) are also being produced upon, for instance, NADPH-oxidase activation in response to growth factor signalling and as a by-product of mitochondrial respiration. H2O2 perturbs the local cellular redox state and this results in specific and reversible cysteine oxidation in target proteins, thereby translating the redox state into a signal that ultimately leads to an appropriate cellular response. This phenomenon of signalling through cysteine oxidation is known as redox signalling and has recently been shown to be involved in a wide range of physiological processes. Cysteine residue oxidation can lead to a range of post-translational modifications, one of which is the formation of intermolecular disulfides. In the present mini-review we will give a number of examples of proteins regulated by intermolecular disulfides and discuss a recently developed method to screen for these interactions. The consequences of the regulation of the FOXO4 (forkhead box O4) transcription factor by formation of intermolecular disulfides with both TNPO1 (transportin 1) and p300/CBP [CREB (cAMP-response-element-binding protein)-binding protein] are discussed in more detail.
Single-molecule fluorescence-based studies on the dynamics, assembly and catalytic mechanism of the spliceosome
Authors: Warnasooriya Chandani , Rueda David
Published: August 2014

Pre-mRNA (precursor mRNA) splicing is a key step in cellular gene expression where introns are excised and exons are ligated together to produce mature mRNA. This process is catalysed by the spliceosome, which consists of five snRNPs (small nuclear ribonucleoprotein particles) and numerous protein factors. Assembly of these snRNPs and associated proteins is a highly dynamic process, making it challenging to study the conformational rearrangements and spliceosome assembly kinetics in bulk studies. In the present review, we discuss recent studies utilizing techniques based on single-molecule detection that have helped overcome this challenge. These studies focus on the assembly dynamics and splicing kinetics in real-time, which help understanding of spliceosomal assembly and catalysis.
Intrinsic and acquired resistance to MEK1/2 inhibitors in cancer
Authors: Sale Matthew J. , Cook Simon J.
Published: August 2014

Recent clinical data with BRAF and MEK1/2 [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase 1/2] inhibitors have demonstrated the remarkable potential of targeting the RAF–MEK1/2–ERK1/2 signalling cascade for the treatment of certain cancers. Despite these advances, however, only a subset of patients respond to these agents in the first instance, and, of those that do, acquired resistance invariably develops after several months. Studies in vitro have identified various mechanisms that can underpin intrinsic and acquired resistance to MEK1/2 inhibitors, and these frequently recapitulate those observed clinically. In the present article, we review these mechanisms and also discuss recent advances in our understanding of how MEK1/2 inhibitor activity is influenced by pathway feedback.
Consensus tracking control of multi‐agent systems with an active virtual leader: time delay case
Authors: Xie Dongmei , Cheng Yongli
Published: August 2014

This paper studies the consensus tracking issue of second‐order multi‐agent systems with an active virtual leader and time delays. We aim to seek the upper bound of time delay τ* such that the multi‐agent systems can achieve the consensus tracking for τ  ∈ [0, τ*). Different methods such as Lyapunov–Razumikhin theory, Hopf bifurcation theory and matrix analysis method are employed to establish the corresponding consensus tracking criteria for continuous‐time and discrete‐time multi‐agent systems, respectively. Finally, numerical examples are given to show the effectiveness of our theoretical results.
Robust distributed model predictive control for uncertain networked control systems
Authors: Zhang Langwen , Wang Jingcheng , Ge Yang , Wang Bohui
Published: August 2014

In this study, an approach to design robust distributed model predictive control (MPC) is proposed for polytopic uncertain networked control systems with time delays. To reduce the computational complexity and improve the flexibility, the entire system is decomposed into multiple smaller dimensional subsystems. For each subsystem, the proposed robust distributed MPC algorithm requires solving multiple linear matrix inequality optimisation problems to minimise an upper bound on a robust performance objective. An augmented polytopic uncertainty description is invoked to handle the input delays. The conservativeness of distributed MPC algorithm is reduced by utilising a sequence of feedback control laws. An iterative on‐line algorithm for robust distributed MPC is developed to coordinate the distributed MPC controllers. Convergence and robust stability of the proposed distributed MPC are investigated. A numerical example is carried out to demonstrate the effectiveness of the proposed algorithm.
Gamma ray measurements with photoconductive detectors using a dense plasma focus
Authors: May M. J. , Brown G. V. , Halvorson C. , Schmidt A. , Bower D. , Tran B. , Lewis P. , Hagen C.
Published: August 2014

Photons in the MeV range emitted from the dense plasma focus (DPF) at the NSTec North Las Vegas Facility have been measured with both neutron-damaged GaAs and natural diamond photoconductive detectors (PCDs). The DPF creates or “pinches” plasmas of various gases (e.g., H2, D2, Ne, Ar., etc.) that have enough energy to create MeV photons from either bremsstrahlung and/or (n,n′) reactions if D2 gas is used. The high bandwidth of the PCDs enabled the first ever measurement of the fast micro-pinches present in DPF plasmas. Comparisons between a slower more conventional scintillator/photomultiplier tube based nuclear physics detectors were made to validate the response of the PCDs to fast intense MeV photon signals. Significant discrepancies in the diamond PCD responses were evident.
Fast penetration of megagauss fields into metallic conductors
Authors: Schnitzer Ory
Published: August 2014

Megagauss magnetic-field penetration into a conducting material is studied via a simplified but representative model, wherein the magnetic-diffusion equation is coupled with a thermal-energy balance. The specific scenario considered is that of a prescribed magnetic field rising (in proportion to an arbitrary power r of time) at the surface of a conducting half-space whose electric conductivity is assumed proportional to an arbitrary inverse power γ of temperature. We employ a systematic asymptotic scheme in which the case of a strong surface field corresponds to a singular asymptotic limit. In this limit, the highly magnetized and hot “skin” terminates at a distinct propagating wave-front. Employing the method of matched asymptotic expansions, we find self-similar solutions of the magnetized region which match a narrow boundary-layer region about the advancing wave front. The rapidly decaying magnetic-field profile in the latter region is also self similar; when scaled by the instantaneous propagation speed, its shape is time-invariant, depending only on the parameter γ. The analysis furnishes a simple asymptotic formula for the skin-depth (i.e., the wave-front position), which substantially generalizes existing approximations. It scales with the power γr + 1∕2 of time and the power γ of field strength, and is much larger than the field-independent skin depth predicted by an athermal model. The formula further involves a dimensionless O(1) pre-factor which depends on r and γ. It is determined by solving a nonlinear eigenvalue problem governing the magnetized region. Another main result of the analysis, apparently unprecedented, is an asymptotic formula for the magnitude of the current-density peak characterizing the wave-front region. Complementary to these systematic results, we provide a closed-form but ad hoc generalization of the theory approximately applicable to arbitrary monotonically rising surface fields. Our results are in excellent agreement with numerical simulations of the model, and compare favourably with detailed magnetohydrodynamic simulations reported in the literature.
Computation of the memory functions in the generalized Langevin models for collective dynamics of macromolecules
Authors: Chen Minxin , Li Xiantao , Liu Chun
Published: August 2014

We present a numerical method to approximate the memory functions in the generalized Langevin models for the collective dynamics of macromolecules. We first derive the exact expressions of the memory functions, obtained from projection to subspaces that correspond to the selection of coarse-grain variables. In particular, the memory functions are expressed in the forms of matrix functions, which will then be approximated by Krylov-subspace methods. It will also be demonstrated that the random noise can be approximated under the same framework, and the second fluctuation-dissipation theorem is automatically satisfied. The accuracy of the method is examined through several numerical examples.
Properties of a planar electric double layer under extreme conditions investigated by classical density functional theory and Monte Carlo simulations
Authors: Zhou Shiqi , Lamperski Stanisław , Zydorczak Maria
Published: August 2014

Monte Carlo (MC) simulation and classical density functional theory (DFT) results are reported for the structural and electrostatic properties of a planar electric double layer containing ions having highly asymmetric diameters or valencies under extreme concentration condition. In the applied DFT, for the excess free energy contribution due to the hard sphere repulsion, a recently elaborated extended form of the fundamental measure functional is used, and coupling of Coulombic and short range hard-sphere repulsion is described by a traditional second-order functional perturbation expansion approximation. Comparison between the MC and DFT results indicates that validity interval of the traditional DFT approximation expands to high ion valences running up to 3 and size asymmetry high up to diameter ratio of 4 whether the high valence ions or the large size ion are co- or counter-ions; and to a high bulk electrolyte concentration being close to the upper limit of the electrolyte mole concentration the MC simulation can deal with well. The DFT accuracy dependence on the ion parameters can be self-consistently explained using arguments of liquid state theory, and new EDL phenomena such as overscreening effect due to monovalent counter-ions, extreme layering effect of counter-ions, and appearance of a depletion layer with almost no counter- and co-ions are observed.
Opsin vs opsin: New materials for biotechnological applications
Authors: Alfinito Eleonora , Reggiani Lino
Published: August 2014

The need of new diagnostic methods satisfying, as an early detection, a low invasive procedure and a cost-efficient value, is orienting the technological research toward the use of bio-integrated devices, in particular, bio-sensors. The set of know-why necessary to achieve this goal is wide, from biochemistry to electronics and is summarized in an emerging branch of electronics, called proteotronics. Proteotronics is here applied to state a comparative analysis of the electrical responses coming from type-1 and type-2 opsins. In particular, the procedure is used as an early investigation of a recently discovered family of opsins, the proteorhodopsins activated by blue light, BPRs. The results reveal some interesting and unexpected similarities between proteins of the two families, suggesting the global electrical response are not strictly linked to the class identity.
Revealing origin of quasi-one dimensional current transport in defect rich two dimensional materials
Authors: Lotz Mikkel R. , Boll Mads , Hansen Ole , Kjær Daniel , Bøggild Peter , Petersen Dirch H.
Published: August 2014

The presence of defects in graphene have for a long time been recognized as a bottleneck for its utilization in electronic and mechanical devices. We recently showed that micro four-point probes may be used to evaluate if a graphene film is truly 2D or if defects in proximity of the probe will lead to a non-uniform current flow characteristic of lower dimensionality. In this work, simulations based on a finite element method together with a Monte Carlo approach are used to establish the transition from 2D to quasi-1D current transport, when applying a micro four-point probe to measure on 2D conductors with an increasing amount of line-shaped defects. Clear 2D and 1D signatures are observed at low and high defect densities, respectively, and current density plots reveal the presence of current channels or branches in defect configurations yielding 1D current transport. A strong correlation is found between the density filling factor and the simulation yield, the fraction of cases with 1D transport and the mean sheet conductance. The upper transition limit is shown to agree with the percolation threshold for sticks. Finally, the conductance of a square sample evaluated with macroscopic edge contacts is compared to the micro four-point probe conductance measurements and we find that the micro four-point probe tends to measure a slightly higher conductance in samples containing defects.
Electric-field effects on magnetic anisotropy and damping constant in Ta/CoFeB/MgO investigated by ferromagnetic resonance
Authors: Okada A. , Kanai S. , Yamanouchi M. , Ikeda S. , Matsukura F. , Ohno H.
Published: August 2014

We investigate electric-field effects on the effective magnetic anisotropy energy density Keff and the Gilbert damping constant α in Ta/CoFeB/MgO structures with CoFeB thickness t ranging from 1.4 to 1.8 nm by ferromagnetic resonance. The electric field-induced modulation ratio of the areal energy density Kefft does not depend on the CoFeB thickness, indicating that the electric-field effect on the magnetic anisotropy originates from the modulation of CoFeB/MgO-interfacial magnetic anisotropy. A clear electric-field modulation of α is observed for the structure with t = 1.4 nm, and almost no modulation for the structures with t ≥ 1.5 nm.
Membrane Protein Structures for Rational Antimicrobial Drug Design
Authors: Walden Patricia M. , McMahon Roisin M. , Archbold Julia K.
Published: August 2014

Antibiotic resistance is a major global health threat. Bacteria have developed novel resistance mechanisms to many of the latest generations of antibiotics and there is an urgent need to develop new therapies to combat these infections. Infections that are caused by multi-drug resistant Gram-negative bacteria result in poor prognosis, prolonged illness, and greater costs for health care. Recent research has pointed to several key bacterial membrane proteins as potential targets for drug and vaccine development. However, determination of the structures of these membrane proteins is not a trivial task. Here we review recent breakthroughs of the structural determination of bacterial membrane proteins and their potential for the future rational design of novel antimicrobial therapies.