bluuebunny/crossref_metadata_2025 huggingface dataset:
Examination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer
Authors: Cathcart Mary-Clare , Gately Kathy , Cummins Robert , Kay Elaine , O'Byrne Kenneth J , Pidgeon Graham P
Published: March 2011

Background

Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. TXS inhibition induces cell death in-vitro, providing a rationale for therapeutic intervention. We aimed to determine the expression profile of TXS in NSCLC and if it is prognostic and/or a survival factor in the disease.

Methods

TXS expression was examined in human NSCLC and matched controls by western analysis and IHC. TXS metabolite (TXB2) levels were measured by EIA. A 204-patient NSCLC TMA was stained for COX-2 and downstream TXS expression. TXS tissue expression was correlated with clinical parameters, including overall survival. Cell proliferation/survival and invasion was examined in NSCLC cells following both selective TXS inhibition and stable TXS over-expression.

Results

TXS was over-expressed in human NSCLC samples, relative to matched normal controls. TXS and TXB2 levels were increased in protein (p < 0.05) and plasma (p < 0.01) NSCLC samples respectively. TXS tissue expression was higher in adenocarcinoma (p < 0.001) and female patients (p < 0.05). No significant correlation with patient survival was observed. Selective TXS inhibition significantly reduced tumour cell growth and increased apoptosis, while TXS over-expression stimulated cell proliferation and invasiveness, and was protective against apoptosis.

Conclusion

TXS is over-expressed in NSCLC, particularly in the adenocarcinoma subtype. Inhibition of this enzyme inhibits proliferation and induces apoptosis. Targeting thromboxane synthase alone, or in combination with conventional chemotherapy is a potential therapeutic strategy for NSCLC.
Mechanisms of oxysterol-induced carcinogenesis
Authors: Jusakul Apinya , Yongvanit Puangrat , Loilome Watcharin , Namwat Nisana , Kuver Rahul
Published: March 2011

Oxysterols are oxidation products of cholesterol that are generated by enzymatic reactions mediated by cytochrome P450 family enzymes or by non-enzymatic reactions involving reactive oxygen and nitrogen species. Oxysterols play various regulatory roles in normal cellular processes such as cholesterol homeostasis by acting as intermediates in cholesterol catabolism. Pathological effects of oxysterols have also been described, and various reports have implicated oxysterols in several disease states, including atherosclerosis, neurological disease, and cancer. Numerous studies show that oxysterols are associated with various types of cancer, including cancers of the colon, lung, skin, breast and bile ducts. The molecular mechanisms whereby oxysterols contribute to the initiation and progression of cancer are an area of active investigation. This review focuses on the current state of knowledge regarding the role of oxysterols in carcinogenesis. Mutagenicity of oxysterols has been described in both nuclear and mitochondrial DNA. Certain oxysterols such as cholesterol-epoxide and cholestanetriol have been shown to be mutagenic and genotoxic. Oxysterols possess pro-oxidative and pro-inflammatory properties that can contribute to carcinogenesis. Oxysterols can induce the production of inflammatory cytokines such as interleukin-8 and interleukin-1β. Certain oxysterols are also involved in the induction of cyclo-oxygenase-2 expression. Inflammatory effects can also be mediated through the activation of liver-X-receptor, a nuclear receptor for oxysterols. Thus, several distinct molecular mechanisms have been described showing that oxysterols contribute to the initiation and progression of cancers arising in various organ systems.
Characterization of proteome alterations in Phanerochaete chrysosporium in response to lead exposure
Authors: Yıldırım Volkan , Özcan Servet , Becher Dörte , Büttner Knut , Hecker Michael , Özcengiz Gülay
Published: March 2011

Background

Total soluble proteome alterations of white rot fungus Phanerochaete chrysosporium in response to different doses (25, 50 and 100 μM) of Pb (II) were characterized by 2DE in combination with MALDI-TOF-MS.

Results

Dose-dependent molecular response to Pb (II) involved a total of 14 up-regulated and 21 down-regulated proteins. The induction of an isoform of glyceraldehyde 3-phosphate dehydrogenase, alcohol dehydrogenase class V, mRNA splicing factor, ATP-dependent RNA helicase, thioredoxin reductase and actin required a Pb (II) dose of at least 50 μM. Analysis of the proteome dynamics of mid-exponential phase cells of P. chrysosporium subjected to 50 μM lead at exposure time intervals of 1, 2, 4 and 8 h, identified a total of 23 proteins in increased and 67 proteins in decreased amount. Overall, the newly induced/strongly up-regulated proteins involved in (i) amelioration of lipid peroxidation products, (ii) defense against oxidative damage and redox metabolism, (iii) transcription, recombination and DNA repair (iv) a yet unknown function represented by a putative protein.

Conclusion

The present study implicated the particular role of the elements of DNA repair, post-tanscriptional regulation and heterotrimeric G protein signaling in response to Pb (II) stress as shown for the first time for a basidiomycete.
Glutamate carboxypeptidase activity in human skin biopsies as a pharmacodynamic marker for clinical studies
Authors: Rojas Camilo , Stathis Marigo , Polydefkis Michael , Rudek Michelle A , Zhao Ming , Ebenezer Gigi J , Slusher Barbara S
Published: March 2011

Background

Glutamate excitotoxicity is thought to be involved in the pathogenesis of neurodegenerative disease. One potential source of glutamate is N-acetyl-aspartyl-glutamate (NAAG) which is hydrolyzed to glutamate and N-acetyl-aspartate (NAA) in a reaction catalyzed by glutamate carboxypeptidase (GCP). As a result, GCP inhibition is thought to be beneficial for the treatment of neurodegenerative diseases where excess glutamate is presumed pathogenic. Both pharmacological and genetic inhibition of GCP has shown therapeutic utility in preclinical models and this has led to GCP inhibitors being pursued for the treatment of nervous system disorders in human clinical trials. Specifically, GCP inhibitors are currently being developed for peripheral neuropathy and neuropathic pain. The purpose of this study was to develop a pharmacodynamic (PD) marker assay to use in clinical development. The PD marker will determine the effect of GCP inhibitors on GCP enzymatic activity in human skin as measure of inhibition in peripheral nerve and help predict drug doses required to elicit pharmacologic responses.

Methods

GCP activity was first characterized in both human skin and rat paw pads. GCP activity was then monitored in both rodent paw pads and sciatic nerve from the same animals following peripheral administration of various doses of GCP inhibitor. Significant differences among measurements were determined using two-tailed distribution, equal variance student's t test.

Results

We describe for the first time, a direct and quantifiable assay to evaluate GCP enzymatic activity in human skin biopsy samples. In addition, we show that GCP activity in skin is responsive to pharmacological manipulation; GCP activity in rodent paws was inhibited in a dose response manner following peripheral administration of a potent and selective GCP inhibitor. Inhibition of GCP activity in rat paw pads was shown to correlate to inhibition of GCP activity in peripheral nerve.

Conclusion

Monitoring GCP activity in human skin after administration of GCP inhibitors could be readily used as PD marker in the clinical development of GCP inhibitors. Enzymatic activity provides a simple and direct measurement of GCP activity from tissue samples easily assessable in human subjects.
Field emission enhancement of Au-Si nano-particle-decorated silicon nanowires
Authors: Zhao Fei , Cheng Guo-an , Zheng Rui-ting , Zhao Dan-dan , Wu Shao-long , Deng Jian-hua
Published: March 2011

Au-Si nano-particle-decorated silicon nanowire arrays have been fabricated by Au film deposition on silicon nanowire array substrates and then post-thermal annealing under hydrogen atmosphere. Field emission measurements illustrated that the turn-on fields of the non-annealed Au-coated SiNWs were 6.02 to 7.51 V/μm, higher than that of the as-grown silicon nanowires, which is about 5.01 V/μm. Meanwhile, after being annealed above 650°C, Au-Si nano-particles were synthesized on the top surface of the silicon nanowire arrays and the one-dimensional Au-Si nano-particle-decorated SiNWs had a much lower turn-on field, 1.95 V/μm. The results demonstrated that annealed composite silicon nanowire array-based electron field emitters may have great advantages over many other emitters.
The molecular dynamic simulation on impact and friction characters of nanofluids with many nanoparticles system
Authors: Lv Jizu , Bai Minli , Cui Wenzheng , Li Xiaojie
Published: March 2011

Impact and friction model of nanofluid for molecular dynamics simulation was built which consists of two Cu plates and Cu-Ar nanofluid. The Cu-Ar nanofluid model consisted of eight spherical copper nanoparticles with each particle diameter of 4 nm and argon atoms as base liquid. The Lennard-Jones potential function was adopted to deal with the interactions between atoms. Thus motion states and interaction of nanoparticles at different time through impact and friction process could be obtained and friction mechanism of nanofluids could be analyzed. In the friction process, nanoparticles showed motions of rotation and translation, but effected by the interactions of nanoparticles, the rotation of nanoparticles was trapped during the compression process. In this process, agglomeration of nanoparticles was very apparent, with the pressure increasing, the phenomenon became more prominent. The reunited nanoparticles would provide supporting efforts for the whole channel, and in the meantime reduced the contact between two friction surfaces, therefore, strengthened lubrication and decreased friction. In the condition of overlarge positive pressure, the nanoparticles would be crashed and formed particles on atomic level and strayed in base liquid.
Growth of carbon nanowalls at atmospheric pressure for one-step gas sensor fabrication
Authors: Yu Kehan , Bo Zheng , Lu Ganhua , Mao Shun , Cui Shumao , Zhu Yanwu , Chen Xinqi , Ruoff Rodney S , Chen Junhong
Published: March 2011

Carbon nanowalls (CNWs), two-dimensional "graphitic" platelets that are typically oriented vertically on a substrate, can exhibit similar properties as graphene. Growth of CNWs reported to date was exclusively carried out at a low pressure. Here, we report on the synthesis of CNWs at atmosphere pressure using "direct current plasma-enhanced chemical vapor deposition" by taking advantage of the high electric field generated in a pin-plate dc glow discharge. CNWs were grown on silicon, stainless steel, and copper substrates without deliberate introduction of catalysts. The as-grown CNW material was mainly mono- and few-layer graphene having patches of O-containing functional groups. However, Raman and X-ray photoelectron spectroscopies confirmed that most of the oxygen groups could be removed by thermal annealing. A gas-sensing device based on such CNWs was fabricated on metal electrodes through direct growth. The sensor responded to relatively low concentrations of NO2 (g) and NH3 (g), thus suggesting high-quality CNWs that are useful for room temperature gas sensors.

PACS: Graphene (81.05.ue), Chemical vapor deposition (81.15.Gh), Gas sensors (07.07.Df), Atmospheric pressure (92.60.hv)
Effect of phonons on the ac conductance of molecular junctions
Authors: Ueda Akiko , Entin-Wohlman Ora , Aharony Amnon
Published: March 2011

We theoretically examine the effect of a single phonon mode on the structure of the frequency dependence of the ac conductance of molecular junctions, in the linear response regime. The conductance is enhanced (suppressed) by the electron-phonon interaction when the chemical potential is below (above) the energy of the electronic state on the molecule.

PACS numbers: 71.38.-k, 73.21.La, 73.23.-b
Ordered GeSi nanorings grown on patterned Si (001) substrates
Authors: Ma Yingjie , Cui Jian , Fan Yongliang , Zhong Zhenyang , Jiang Zuimin
Published: March 2011

An easy approach to fabricate ordered pattern using nanosphere lithography and reactive iron etching technology was demonstrated. Long-range ordered GeSi nanorings with 430 nm period were grown on patterned Si (001) substrates by molecular beam epitaxy. The size and shape of rings were closely associated with the size of capped GeSi quantum dots and the Si capping processes. Statistical analysis on the lateral size distribution shows that the high growth temperature and the long-term annealing can improve the uniformity of nanorings.

PACS code1·PACS code2·more

Mathematics Subject Classification (2000) MSC code1·MSC code2·more
Mixed convective boundary layer flow over a vertical wedge embedded in a porous medium saturated with a nanofluid: Natural Convection Dominated Regime
Authors: Gorla Rama Subba Reddy , Chamkha Ali Jawad , Rashad Ahmed Mohamed
Published: March 2011

A boundary layer analysis is presented for the mixed convection past a vertical wedge in a porous medium saturated with a nano fluid. The governing partial differential equations are transformed into a set of non-similar equations and solved numerically by an efficient, implicit, iterative, finite-difference method. A parametric study illustrating the influence of various physical parameters is performed. Numerical results for the velocity, temperature, and nanoparticles volume fraction profiles, as well as the friction factor, surface heat and mass transfer rates have been presented for parametric variations of the buoyancy ratio parameter Nr, Brownian motion parameter Nb, thermophoresis parameter Nt, and Lewis number Le. The dependency of the friction factor, surface heat transfer rate (Nusselt number), and mass transfer rate (Sherwood number) on these parameters has been discussed.
Intracerebral infection with dengue-3 virus induces meningoencephalitis and behavioral changes that precede lethality in mice
Authors: Amaral Debora CG , Rachid Milene A , Vilela Marcia C , Campos Roberta DL , Ferreira Gustavo P , Rodrigues David H , Lacerda-Queiroz Norinne , Miranda Aline S , Costa Vivian V , Campos Marco A , Kroon Erna G , Teixeira Mauro M , Teixeira Antonio L
Published: March 2011

Background

Dengue, one of the most important arboviral diseases of humans, may cause severe systemic disease. Although dengue virus (DENV) has been considered to be a non-neurotropic virus, dengue infection has been associated recently with a series of neurological syndromes, including encephalitis. In this work, we evaluated behavioral changes and inflammatory parameters in C57BL/6 mice infected with non-adapted dengue virus 3 (DENV-3) genotype I.

Methods

C57BL/6 mice received 4 × 103 PFU of DENV-3 by an intracranial route. We evaluated the trafficking of leukocytes in brain microvasculature using intravital microscopy, and evaluated chemokine and cytokine profiling by an ELISA test at 3 and 6 days post infection (p.i.). Furthermore, we determined myeloperoxidase activity and immune cell populations, and also performed histopathological analysis and immunostaining for the virus in brain tissue.

Results

All animals developed signs of encephalitis and died by day 8 p.i. Motor behavior and muscle tone and strength parameters declined at day 7 p.i. We observed increased leukocyte rolling and adhesion in brain microvasculature of infected mice at days 3 and 6 p.i. The infection was followed by significant increases in IFN-γ, TNF-α, CCL2, CCL5, CXCL1, and CXCL2. Histological analysis showed evidence of meningoencephalitis and reactive gliosis. Increased numbers of neutrophils, CD4+ and CD8+ T cells were detected in brain of infected animals, notably at day 6 p.i. Cells immunoreactive for anti-NS-3 were visualized throughout the brain.

Conclusion

Intracerebral infection with non-adapted DENV-3 induces encephalitis and behavioral changes that precede lethality in mice.
Clustering based on adherence data
Authors: Kiwuwa-Muyingo Sylvia , Oja Hannu , Walker Sarah A , Ilmonen Pauliina , Levin Jonathan , Todd Jim
Published: March 2011

Adherence to a medical treatment means the extent to which a patient follows the instructions or recommendations by health professionals. There are direct and indirect ways to measure adherence which have been used for clinical management and research. Typically adherence measures are monitored over a long follow-up or treatment period, and some measurements may be missing due to death or other reasons. A natural question then is how to describe adherence behavior over the whole period in a simple way. In the literature, measurements over a period are usually combined just by using averages like percentages of compliant days or percentages of doses taken. In the paper we adapt an approach where patient adherence measures are seen as a stochastic process. Repeated measures are then analyzed as a Markov chain with finite number of states rather than as independent and identically distributed observations, and the transition probabilities between the states are assumed to fully describe the behavior of a patient. The patients can then be clustered or classified using their estimated transition probabilities. These natural clusters can be used to describe the adherence of the patients, to find predictors for adherence, and to predict the future events. The new approach is illustrated and shown to be useful with a simple analysis of a data set from the DART (Development of AntiRetroviral Therapy in Africa) trial in Uganda and Zimbabwe.
Comparison of the efficacy of tenofovir and adefovir in the treatment of chronic hepatitis B: A Systematic Review
Authors: Zhao Shu-Shan , Tang Lan-Hua , Dai Xia-Hong , Wang Wei , Zhou Rong-Rong , Chen Li-Zhang , Fan Xue-Gong
Published: March 2011

Chronic viral hepatitis B remains a global public health concern. Currently, several drugs, such as tenofovir and adefovir, are recommended for treatment of patients with chronic hepatitis B. tenofovir is a nucleoside analog with selective activity against hepatitis b virus and has been shown to be more potent in vitro than adefovir. But the results of trials comparing tenofovir and adefovir in the treatment of chronic hepatitis B were inconsistent. However, there was no systematic review on the comparison of the efficacy of tenofovir and adefovir in the treatment of chronic hepatitis B. To evaluate the comparison of the efficacy of tenofovir and adefovir in the treatment of chronic hepatitis B we conducted a systematic review and meta-analysis of clinical trials. We searched PUBMED, Web of Science, EMBASE, CNKI, VIP database, WANFANG database, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Review. Finally six studies were left for analysis which involved 910 patients in total, of whom 576 were included in tenofovir groups and 334 were included in adefovir groups. At the end of 48-week treatment, tenofovir was superior to adefovir at the HBV-DNA suppression in patients[RR = 2.59; 95%CI(1.01-6.67), P = 0.05]. While there was no significant difference in the ALT normalization[RR = 1.15; 95%CI(0.96-1.37), P = 0.14], HBeAg seroconversion[RR = 1.32; 95%CI(1.00-1.75), P = 0.05] and HBsAg loss rate[RR = 1.19; 95%CI(0.74-1.91), P = 0.48]. More high-quality, well-designed, randomized controlled, multi-center trails are clearly needed to guide evolving standards of care for chronic hepatitis B.
Anthocyanidins-enriched bilberry extracts inhibit 3T3-L1 adipocyte differentiation via the insulin pathway
Authors: Suzuki Rieko , Tanaka Masami , Takanashi Masakatsu , Hussain Aashiq , Yuan Bo , Toyoda Hiroo , Kuroda Masahiko
Published: March 2011

Background

Obesity and metabolic syndrome are important public concerns, and there is increasing demand for effective therapeutic strategies. Flavonoids are expected to improve the risk factors associated with metabolic syndrome. Anthocyanidins are a kind of flavonoids; well known for their anti-oxidative, anti-inflammatory and anti-tumor properties. However, their effects on adipocytes and molecular systems are not well defined. In this study, we examined the effects of anthocyanidins-enriched bilberry extracts on adipocyte differentiation.

Methods

Utilizing 3T3-L1 cell line, we investigated that bilberry extracts and anthocyanidins induced inhibition of lipid accumulation during adipogenesis. To identify what is the most important bilberry mediated-effect, we analyzed the expressions of key transcriptional factors associated with adipocyte differentiation by Real Time (RT)-PCR. From the results of RT-PCR, we hypothesized that bilberry extracts and anthocyanidins blocks insulin signal, we determined the phosphorylation of tyrosine residues of insulin receptor substrate 1 (IRS1) protein by western blotting analysis. In addition, we compared the whole-genome expression profiles of early stage of adipocyte differentiation under four different growth conditions (DMSO, bilberry, two anthocyanidins) by microarray analyses and Gene Set Enrichment Analysis (GSEA).

Results

Exposure to bilberry extracts and anthocyanidins during adipocyte differentiation inhibited 3T3-L1 differentiation. During this period, bilberry extracts and anthocyanidin significantly decreased a key adipocyte differentiation-associated marker, peroxisome proliferator-activated receptor- γ (Ppar γ ) and sterol regulatory element-binding protein 1c (Srebp1c). Western blotting analysis showed that bilberry extracts and anthocyanidin decreased the phosphorylation of tyrosine residues of IRS1. In addition, microarray experiments and GSEA data revealed significantly altered expression of the known genes of the insulin pathway in cells treated with bilberry extracts or anthocyanidins in the early differentiation stages.

Conclusions

Our data demonstrate that anthocyanidin enriched bilberry extracts strongly inhibit the adipocyte differentiation via the insulin pathway. Furthermore, bilberry extracts might be used as a potential complementary treatment for the obese patients with metabolic syndrome.
Validation of a single biopsy approach and bolus protein feeding to determine myofibrillar protein synthesis in stable isotope tracer studies in humans
Authors: Burd Nicholas A , West Daniel WD , Rerecich Tracy , Prior Todd , Baker Steven K , Phillips Stuart M
Published: March 2011

Background

Minimizing the number of muscle biopsies has important methodological implications and minimizes subject discomfort during a stable isotope amino acid infusion. We aimed to determine the reliability of obtaining a single muscle biopsy for the calculation of muscle protein fractional synthetic rate (FSR) as well as the amount of incorporation time necessary to obtain that biopsy after initiating a stable isotope infusion (Study 1). The calculation of muscle protein FSR requires tracer steady-state during the stable isotope infusion. Therefore, a second aim was to examine if steady-state conditions are compromised in the precursor pools (plasma free or muscle intracellular [IC]) after ingestion of a tracer enriched protein drink and after resistance exercise (Study 2).

Methods

Sixteen men (23 ± 3 years; BMI = 23.8 ± 2.2 kg/m2, means ± SD) were randomized to perform Study 1 or Study 2 (n = 8, per study). Subjects received a primed, constant infusion of L-[ring-13C6]phenylalanine coupled with muscle biopsies of the vastus lateralis to measure rates of myofibrillar protein synthesis (MPS). Subjects in Study 2 were fed 25 g of whey protein immediately after an acute bout of unilateral resistance exercise.

Results

There was no difference (P = 0.3) in rates of MPS determined using the steady-state precursor-product equation and determination of tracer incorporation between sequential biopsies 150 min apart or using plasma protein as the baseline enrichment, provided the infusion length was sufficient (230 ± 0.3 min). We also found that adding a modest amount of tracer (4% enriched), calculated based on the measured phenylalanine content of the protein (3.5%) in the drink, did not compromise steady-state conditions (slope of the enrichment curve not different from zero) in the plasma free or, more importantly, the IC pool (both P > 0.05).

Conclusions

These data demonstrate that the single biopsy approach yields comparable rates of muscle protein synthesis, provided a longer incorporation time is utilized, to that seen with a traditional two biopsy approach. In addition, we demonstrate that enriching protein-containing drinks with tracer does not disturb isotopic steady-state and thus both are reliable techniques to determine rates of MPS in humans.
Initiation of health-behaviour change among employees participating in a web-based health risk assessment with tailored feedback
Authors: Colkesen Ersen B , Niessen Maurice AJ , Peek Niels , Vosbergen Sandra , Kraaijenhagen Roderik A , van Kalken Coenraad K , Tijssen Jan GP , Peters Ron JG
Published: March 2011

Background

Primary prevention programs at the worksite can improve employee health and reduce the burden of cardiovascular disease. Programs that include a web-based health risk assessment (HRA) with tailored feedback hold the advantage of simultaneously increasing awareness of risk and enhancing initiation of health-behaviour change. In this study we evaluated initial health-behaviour change among employees who voluntarily participated in such a HRA program.

Methods

We conducted a questionnaire survey among 2289 employees who voluntarily participated in a HRA program at seven Dutch worksites between 2007 and 2009. The HRA included a web-based questionnaire, biometric measurements, laboratory evaluation, and tailored feedback. The survey questionnaire assessed initial self-reported health-behaviour change and satisfaction with the web-based HRA, and was e-mailed four weeks after employees completed the HRA.

Results

Response was received from 638 (28%) employees. Of all, 86% rated the program as positive, 74% recommended it to others, and 58% reported to have initiated overall health-behaviour change. Compared with employees at low CVD risk, those at high risk more often reported to have increased physical activity (OR 3.36, 95% CI 1.52-7.45). Obese employees more frequently reported to have increased physical activity (OR 3.35, 95% CI 1.72-6.54) and improved diet (OR 3.38, 95% CI 1.50-7.60). Being satisfied with the HRA program in general was associated with more frequent self-reported initiation of overall health-behaviour change (OR 2.77, 95% CI 1.73-4.44), increased physical activity (OR 1.89, 95% CI 1.06-3.39), and improved diet (OR 2.89, 95% CI 1.61-5.17).

Conclusions

More than half of the employees who voluntarily participated in a web-based HRA with tailored feedback, reported to have initiated health-behaviour change. Self-reported initiation of health-behaviour change was more frequent among those at high CVD risk and BMI levels. In general employees reported to be satisfied with the HRA, which was also positively associated with initiation of health-behaviour change. These findings indicate that among voluntary participating employees a web-based HRA with tailored feedback may motivate those in greatest need of health-behaviour change and may be a valuable component of workplace health promotion programs.
Ethnobotanical study of indigenous knowledge on medicinal plant use by traditional healers in Oshikoto region, Namibia
Authors: Cheikhyoussef Ahmad , Shapi Martin , Matengu Kenneth , Mu Ashekele Hina
Published: March 2011

Background

The objective of this study was to establish a regional profile of the indigenous knowledge system (IKS) for medicinal plant use and cultural practices associated with the healing process of these plants by traditional healers in the Oshikoto region, Namibia.

Methods

An ethnobotanical survey was undertaken to collect information from traditional healers during September and October 2008. Data was collected through the use of questionnaires and personal interviews during field trips in the ten constituencies of the Oshikoto region. A total of 47 respondents were interviewed with most of them aged 66 and above.

Results

The traditional healers in Oshikoto region use 61 medicinal plant species that belong to 25 families for the treatment of various diseases and disorders with the highest number of species being used for mental diseases followed by skin infection and external injuries. Trees (28 species) were found to be the most used plants followed by herbs (15 species), shrubs (10 species) and climbers (4 species). The average of the informant consensus factor (FIC) value for all ailment categories was 0.75. High FIC values were obtained for Pergularia daemia, and Tragia okanyua, which were reported to treat weakness and dizziness problems, snake bite, swelling and cardiovascular problems indicating that these species traditionally used to treat these ailments are worth examining for bioactive compounds.

Conclusions

The traditional healers in Oshikoto possess rich ethno-pharmacological knowledge. This study allows for identifying many high value medicinal plant species, indicating high potential for economic development through sustainable collection of these medicinal plants.
Mosquito salivary gland protein preservation in the field for immunological and biochemical analysis
Authors: Fontaine A , Pascual A , Diouf I , Bakkali N , Bourdon S , Fusai T , Rogier C , Almeras L
Published: March 2011

Mosquito salivary proteins are involved in several biological processes that facilitate their blood feeding and have also been reported to elicit an IgG response in vertebrates. A growing number of studies have focused on this immunological response for its potential use as a biological marker of exposure to arthropod bites. As mosquito saliva collection is extremely laborious and inefficient, most research groups prefer to work on mosquito salivary glands (SGs). Thus, SG protein integrity is a critical factor in obtaining meaningful data from immunological and biochemical analysis. Current methodologies rely on an immediate freezing of SGs after their collection. However, the maintenance of samples in a frozen environment can be hard to achieve in field conditions. In this study, SG proteins from two mosquito species (Aedes aegyptiandAnopheles gambiae s.s.) stored in different media for 5 days at either +4°C or room temperature (RT) were evaluated at the quantitative (i.e., ELISA) and qualitative (i.e., SDS-PAGE and immunoblotting) levels. Our results indicated that PBS medium supplemented with an anti-protease cocktail seems to be the best buffer to preserve SG antigens for 5 days at +4°C for ELISA analysis. Conversely, cell-lysis buffer (Urea-Thiourea-CHAPS-Tris) was best at preventing protein degradation both at +4°C and RT for further qualitative analysis. These convenient storage methods provide an alternative to freezing and are expected to be applicable to other biological samples collected in the field.
Mining semantic networks of bioinformatics e-resources from the literature
Authors: Afzal Hammad , Eales James , Stevens Robert , Nenadic Goran
Published: March 2011

Background

There have been a number of recent efforts (e.g. BioCatalogue, BioMoby) to systematically catalogue bioinformatics tools, services and datasets. These efforts rely on manual curation, making it difficult to cope with the huge influx of various electronic resources that have been provided by the bioinformatics community. We present a text mining approach that utilises the literature to automatically extract descriptions and semantically profile bioinformatics resources to make them available for resource discovery and exploration through semantic networks that contain related resources.

Results

The method identifies the mentions of resources in the literature and assigns a set of co-occurring terminological entities (descriptors) to represent them. We have processed 2,691 full-text bioinformatics articles and extracted profiles of 12,452 resources containing associated descriptors with binary and tf*idf weights. Since such representations are typically sparse (on average 13.77 features per resource), we used lexical kernel metrics to identify semantically related resources via descriptor smoothing. Resources are then clustered or linked into semantic networks, providing the users (bioinformaticians, curators and service/tool crawlers) with a possibility to explore algorithms, tools, services and datasets based on their relatedness. Manual exploration of links between a set of 18 well-known bioinformatics resources suggests that the method was able to identify and group semantically related entities.

Conclusions

The results have shown that the method can reconstruct interesting functional links between resources (e.g. linking data types and algorithms), in particular when tf*idf-like weights are used for profiling. This demonstrates the potential of combining literature mining and simple lexical kernel methods to model relatedness between resource descriptors in particular when there are few features, thus potentially improving the resource description, discovery and exploration process. The resource profiles are available at http://gnode1.mib.man.ac.uk/bioinf/semnets.html
The Role of XPG in Processing (CAG)n/(CTG)n DNA Hairpins
Authors: Hou Caixia , Zhang Tianyi , Tian Lei , Huang Jian , Gu Liya , Li Guo-Min
Published: March 2011

Background

During DNA replication or repair, disease-associated (CAG)n/(CTG)n expansion can result from formation of hairpin structures in the repeat tract of the newly synthesized or nicked DNA strand. Recent studies identified a nick-directed (CAG)n/(CTG)n hairpin repair (HPR) system that removes (CAG)n/(CTG)n hairpins from human cells via endonucleolytic incisions. Because the process is highly similar to the mechanism by which XPG and XPF endonucleases remove bulky DNA lesions during nucleotide excision repair, we assessed the potential role of XPG in conducting (CAG)n/(CTG)n HPR.

Results

To determine if the XPG endonuclease is involved in (CAG)n/(CTG)n hairpin removal, two XPG-deficient cell lines (GM16024 and AG08802) were examined for their ability to process (CAG)n/(CTG)n hairpins in vitro. We demonstrated that the GM16024 cell line processes all hairpin substrates as efficiently as HeLa cells, and that the AG08802 cell line is partially defective in HPR. Analysis of repair intermediates revealed that nuclear extracts from both XPG-deficient lines remove CAG/CTG hairpins via incisions, but the incision products are distinct from those generated in HeLa extracts. We also show that purified recombinant XPG protein greatly stimulates HPR in XPG-deficient extracts by promoting an incision 5' to the hairpin.

Conclusions

Our results strongly suggest that 1) human cells possess multiple pathways to remove (CAG)n/(CTG)n hairpins located in newly synthesized (or nicked) DNA strand; and 2) XPG, although not essential for (CAG)n/(CTG)n hairpin removal, stimulates HPR by facilitating a 5' incision to the hairpin. This study reveals a novel role for XPG in genome-maintenance and implicates XPG in diseases caused by trinucleotide repeat expansion.
Activated protein C in septic shock: a propensity-matched analysis
Authors: Sadaka Farid , O'Brien Jacklyn , Migneron Matthew , Stortz Julie , Vanston Alexander , Taylor Robert W
Published: March 2011

Introduction

The use of human recombinant activated protein C (rhAPC) for the treatment of severe sepsis remains controversial despite multiple reported trials. The efficacy of rhAPC remains a matter of dispute. We hypothesized that patients with septic shock who were treated with rhAPC had an improved in-hospital mortality compared to patients with septic shock with similar acuity who did not receive rhAPC.

Methods

This retrospective cohort study was completed at a large university-affiliated hospital. All patients with septic shock admitted to a 50-bed ICU between July 2003 and February 2009 were included. Patients were treated according to sepsis management guidelines.

Results

A total of 563 septic shock patients were included (110 received rhAPC and 453 did not). Treated and untreated groups were matched in patient characteristics, comorbidities, and physiologic variables in a 1:1 propensity-matched analysis (108 received rhAPC, 108 did not). Mean Acute Physiology And Chronic Health Evaluation II (APACHE II) scores were 24.5 for the matched treated and 23.9 for the matched untreated group (P = 0.54). Receipt of rhAPC was associated with reduced in-hospital mortality (35.2% vs. 53.8%, P = 0.005), similar mean days on vasopressors (2 vs. 2, P = 0.90), similar mean days on mechanical ventilation (9 vs. 8.7, P = 0.80), similar mean length of ICU stay in days (11.0 vs. 11.3, P = 0.90), and similar mean length of hospital stay in days (19.5 vs 27, P = 0.11). No patients in either group had intracranial bleeding; differences in gastrointestinal bleeding and transfusion requirements were not statistically significant.

Conclusions

Patients in our institution with septic shock who were treated with rhAPC had a reduced in-hospital mortality compared with patients with septic shock with similar acuity who were not treated with rhAPC. In addition, time on mechanical ventilation, time on vasopressors, lengths of stay and bleeding complications did not differ between the groups.
Acute respiratory failure in kidney transplant recipients: a multicenter study
Authors: Canet Emmanuel , Osman David , Lambert Jérome , Guitton Christophe , Heng Anne-Elisabeth , Argaud Laurent , Klouche Kada , Mourad Georges , Legendre Christophe , Timsit Jean-François , Rondeau Eric , Hourmant Maryvonne , Durrbach Antoine , Glotz Denis , Souweine Bertrand , Schlemmer Benoît , Azoulay Elie
Published: March 2011

Introduction

Data on pulmonary complications in renal transplant recipients are scarce. The aim of this study was to evaluate acute respiratory failure (ARF) in renal transplant recipients.

Methods

We conducted a retrospective observational study in nine transplant centers of consecutive kidney transplant recipients admitted to the intensive care unit (ICU) for ARF from 2000 to 2008.

Results

Of 6,819 kidney transplant recipients, 452 (6.6%) required ICU admission, including 200 admitted for ARF. Fifteen (7.5%) of these patients had combined kidney-pancreas transplantations. The most common causes of ARF were bacterial pneumonia (35.5%), cardiogenic pulmonary edema (24.5%) and extrapulmonary acute respiratory distress syndrome (ARDS) (15.5%). Pneumocystis pneumonia occurred in 11.5% of patients. Mechanical ventilation was used in 93 patients (46.5%), vasopressors were used in 82 patients (41%) and dialysis was administered in 104 patients (52%). Both the in-hospital and 90-day mortality rates were 22.5%. Among the 155 day 90 survivors, 115 patients (74.2%) were dialysis-free, including 75 patients (65.2%) who recovered prior renal function. Factors independently associated with in-hospital mortality were shock at admission (odds ratio (OR) 8.70, 95% confidence interval (95% CI) 3.25 to 23.29), opportunistic fungal infection (OR 7.08, 95% CI 2.32 to 21.60) and bacterial infection (OR 2.53, 95% CI 1.07 to 5.96). Five factors were independently associated with day 90 dialysis-free survival: renal Sequential Organ Failure Assessment (SOFA) score on day 1 (OR 0.68/SOFA point, 95% CI 0.52 to 0.88), bacterial infection (OR 0.43, 95% CI 0.21 to 0.90), three or four quadrants involved on chest X-ray (OR 0.44, 95% CI 0.21 to 0.91), time from hospital to ICU admission (OR 0.98/day, 95% CI 0.95 to 0.99) and oxygen flow at admission (OR 0.93/liter, 95% CI 0.86 to 0.99).

Conclusions

In kidney transplant recipients, ARF is associated with high mortality and graft loss rates. Increased Pneumocystis and bacterial prophylaxis might improve these outcomes. Early ICU admission might prevent graft loss.
The acute management of trauma hemorrhage: a systematic review of randomized controlled trials
Authors: Curry Nicola , Hopewell Sally , Dorée Carolyn , Hyde Chris , Brohi Karim , Stanworth Simon
Published: March 2011

Introduction

Worldwide, trauma is a leading cause of death and disability. Haemorrhage is responsible for up to 40% of trauma deaths. Recent strategies to improve mortality rates have focused on optimal methods of early hemorrhage control and correction of coagulopathy. We undertook a systematic review of randomized controlled trials (RCT) which evaluated trauma patients with hemorrhagic shock within the first 24 hours of injury and appraised how the interventions affected three outcomes: bleeding and/or transfusion requirements; correction of trauma induced coagulopathy and mortality.

Methods

Comprehensive searches were performed of MEDLINE, EMBASE, CENTRAL (The Cochrane Library Issue 7, 2010), Current Controlled Trials, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP) and the National Health Service Blood and Transplant Systematic Review Initiative (NHSBT SRI) RCT Handsearch Database.

Results

A total of 35 RCTs were identified which evaluated a wide range of clinical interventions in trauma hemorrhage. Many of the included studies were of low methodological quality and participant numbers were small. Bleeding outcomes were reported in 32 studies; 7 reported significantly reduced transfusion use following a variety of clinical interventions, but this was not accompanied by improved survival. Minimal information was found on traumatic coagulopathy across the identified RCTs. Overall survival was improved in only three RCTs: two small studies and a large study evaluating the use of tranexamic acid.

Conclusions

Despite 35 RCTs there has been little improvement in outcomes over the last few decades. No clear correlation has been demonstrated between transfusion requirements and mortality. The global trauma community should consider a coordinated and strategic approach to conduct well designed studies with pragmatic endpoints.
Role for IL-10 in inducing functional impairment of monocytes upon TLR4 ligation in patients with chronic HCV infections
Authors: Liu Bi-Sheng , Groothuismink Zwier M A , Janssen Harry L A , Boonstra André
Published: March 2011

The consequences of chronic infection with the HCV on immunity to distinct pathogens are not fully appreciated, despite the potent modulatory effects of HCV on the immune system. We observed that upon TLR4 ligation, monocytes from chronic HCV patients demonstrated three to five times lower TNF and IL-12p40 production as compared with healthy individuals. However, augmented production of TNF, IL-12p40, and IL-12p70 by monocytes was observed upon stimulation with R848. Importantly, we observed that the levels of IL-10 in chronic HCV patients are higher in serum and that more IL-10 is produced by monocytes as compared with healthy individuals. The inhibitory effect of IL-10 on the production of proinflammatory cytokines by monocytes was only observed upon LPS stimulation but not upon R848 stimulation, showing that only the TLR4 pathway in monocytes is sensitive to the suppressive effects of IL-10. Interestingly, monocytes stimulated with the TLR4 agonist, but not TLR8 agonist, produced higher levels of IL-10 when exposed to patient serum as compared with serum from healthy individuals. Our results indicate that by differentially affecting TLR4 and TLR8 pathways, IL-10 may mediate highly selective modulation of the function of monocytes observed in chronic HCV patients. This suggests that there is no overall increased susceptibility to pathogens but a specific suppression of the functionality of TLR4 signaling pathway in monocytes, which is, at least partly, mediated via IL-10.
Amine-reactive OVA multimers for auto-vaccination against cytokines and other mediators: perspectives illustrated for GCP-2 inL. majorinfection
Authors: Uyttenhove Catherine , Marillier Reece G , Tacchini-Cottier Fabienne , Charmoy Mélanie , Caspi Rachel R , Damsker Jesse M , Goriely Stanislas , Su Dan , Van Damme Jo , Struyf Sofie , Opdenakker Ghislain , Van Snick Jacques
Published: March 2011

Anticytokine auto-vaccination is a powerful tool for the study of cytokine functions in vivo but has remained rather esoteric as a result of numerous technical difficulties. We here describe a two-step procedure based on the use of OVA multimers purified by size exclusion chromatography after incubation with glutaraldehyde at pH 6. When such polymers are incubated with a target protein at pH 8.5 to deprotonate reactive amines, complexes are formed that confer immunogenicity to self-antigens. The chemokine GCP-2/CXCL6, the cytokines GM-CSF, IL-17F, IL-17E/IL-25, IL-27, and TGF-β1, and the MMP-9/gelatinase B are discussed as examples. mAb, derived from such immunized mice, have obvious advantages for in vivo studies of the target proteins. Using a mAb against GCP-2, obtained by the method described here, we provide the first demonstration of the major role played by this chemokine in rapid neutrophil mobilization after Leishmania major infection. Pre-activated OVA multimers reactive with amine residues thus provide an efficient carrier for auto-vaccination against 9–90 kDa autologous proteins.
GEOPHYSICS BRIGHT SPOTS
Authors: Mahrer Ken
Published: March 2011

Greetings but yet again friends, and welcome back to another edition of Bright Spots, your friendly GEOPHYSICS spotlighter. Last time this column came to you via the hard work of a band of Associate Editors (AE) of GEOPHYSICS. They spotlighted the articles. This month we feature both AE and my choices. I hope our choices motivate you to immerse yourself in the originals and their friends in the January-February 2011 issue. It will be worth the effort. Remember, learning is not just a selfish effort; it includes absorbing the sunshine of others' successes. Thanks to all.
Androgenic Influence on Serotonergic Activation of the HPA Stress Axis
Authors: Goel Nirupa , Plyler Kimberly S. , Daniels Derek , Bale Tracy L.
Published: March 2011

The higher incidence of stress-mediated affective disorders in women may be a function of gonadal hormone influence on complex interactions between serotonin and neural circuits that mediate the hypothalamic-pituitary-adrenal (HPA) stress axis. The paraventricular nucleus of the hypothalamus (PVN) receives serotonergic innervation, and selective serotonin reuptake inhibitors such as citalopram activate the HPA axis independent of stress. We have previously demonstrated that the magnitude of this serotonergic activation was greater in females and was attenuated by testosterone administration; however, the potential central sites of action where androgens reduce these serotonergic effects have not been determined. Therefore, we examined a time course of corticosterone production and used central c-Fos protein levels to assay neuronal activation in stress-related brain regions in female, male, and gonadectomized male mice after an acute citalopram injection (15 mg/kg). In the hippocampus, c-Fos-immunoreactivity was greater in males than in females or gonadectomized males. This same pattern emerged in the lateral septum after vehicle and gonadectomy reversed the effect of citalopram. These regions are important for inhibitory influences on the PVN, and accordingly, hippocampal c-Fos levels were negatively correlated with corticosterone production. No sex differences in c-Fos were detected in the PVN, cingulate cortex, or paraventricular thalamus in response to vehicle or citalopram. These data support brain region-specific regulation of the HPA axis where sex differences may be mediated partly through androgen enhancement of signaling in inhibitory regions.