bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Computer Simulation Approach to Assessing Therapeutic Intervention Points for the Prevention of Cytokine‐Induced Cartilage Breakdown
Authors: Proctor C. J. , Macdonald C. , Milner J. M. , Rowan A. D. , Cawston T. E. 
Published: November 2013

ObjectiveTo use a novel computational approach to examine the molecular pathways involved in cartilage breakdown and to use computer simulation to test possible interventions for reducing collagen release.MethodsWe constructed a computational model of the relevant molecular pathways using the Systems Biology Markup Language, a computer‐readable format of a biochemical network. The model was constructed using our experimental data showing that interleukin‐1 (IL‐1) and oncostatin M (OSM) act synergistically to up‐regulate collagenase protein levels and activity and initiate cartilage collagen breakdown. Simulations were performed using the COPASI software package.ResultsThe model predicted that simulated inhibition of JNK or p38 MAPK, and overexpression of tissue inhibitor of metalloproteinases 3 (TIMP‐3) led to a reduction in collagen release. Overexpression of TIMP‐1 was much less effective than that of TIMP‐3 and led to a delay, rather than a reduction, in collagen release. Simulated interventions of receptor antagonists and inhibition of JAK‐1, the first kinase in the OSM pathway, were ineffective. So, importantly, the model predicts that it is more effective to intervene at targets that are downstream, such as the JNK pathway, rather than those that are close to the cytokine signal. In vitro experiments confirmed the effectiveness of JNK inhibition.ConclusionOur study shows the value of computer modeling as a tool for examining possible interventions by which to reduce cartilage collagen breakdown. The model predicts that interventions that either prevent transcription or inhibit the activity of collagenases are promising strategies and should be investigated further in an experimental setting.
Duration of the South America summer monsoon is increasing
Authors: Rao V. Brahmananda , Franchito Sergio H. , Gan Manoel A. , Gerolamo Renato O. P. 
Published: November 2013

AbstractWe studied the interannual variability of the beginning, end and duration of South American monsoon system (SAMS) for the period 1956–2006. The mean beginning date was 10 October, whereas the mean end date was 6 April, and the mean duration was 174 days. The beginning of SAMS showed a tendency to start earlier and the end date showed a tendency to delay; thus, the duration of SAMS showed a tendency to increase by about 7 days in 10 years. We found that the beginning and end dates of SAMS have significant positive correlation with sea surface temperature (SST) of an earlier period at southwest Africa in the South Atlantic Ocean. This suggests the potential of SST in the prediction of the beginning and end dates of SAMS.
Quercetin‐3‐rhamnoglucoside (rutin) stimulates transport of organic anion compounds mediated by organic anion transporting polypeptide 2B1
Authors: Ogura Jiro , Koizumi Takahiro , Segawa Masahiro , Yabe Keisuke , Kuwayama Kaori , Sasaki Shunichi , Kaneko Chihiro , Tsujimoto Takashi , Kobayashi Masaki , Yamaguchi Hiroaki , Iseki Ken 
Published: November 2013

ABSTRACTQuercetin‐3‐rhamnoglucoside (rutin) has a wide spectrum of biochemical and pharmacological activities. Rutin is absorbed mainly in its unmetabolized form. Organic anion transporting polypeptide (OATP) 2B1 is a major uptake transporter in the intestine. Thus, it is important for the prevention of adverse events to understand drug interactions mediated by OATP2B1 in the absorption process. This study assessed the effect of rutin on transport by OATP2B1. Rutin stimulated the uptake of estrone‐3‐sulfate (E‐3‐S), taurocholic acid (TCA), cholic acid (CA) and rosuvastatin by OATP2B1, but not p‐coumaric acid or ferulic acid. The EC50 of rutin for transport by OATP2B1 was 2.32 μm. The Km value of E‐3‐S for OATP2B1 in the presence of rutin (9.21 μm) was almost the same as that in the absence of rutin (8.53 μm). On the other hand, the Vmax of E‐3‐S transport by OATP2B1 in the presence of rutin (270 pmol/mg protein/min) was 1.2‐fold higher than that in the absence of rutin (218 pmol/mg protein/min). Moreover, the expression level of OATP2B1 on the cell membrane was increased by treatment with rutin for 5 min without alteration of the total OATP2B1 expression level. Moreover, the increase in the localization of OATP2B1 at the cell surface was detected by the immunocytochemistry. The stimulatory effect of rutin is a little weak but may affect the absorption of OATP2B1 substrates, because rutin is taken daily in foods and its intestinal concentration would reach the stimulatory range of OATP2B1. Copyright © 2014 John Wiley & Sons, Ltd.
Peroxynitrite, a potent macrophage‐derived oxidizing cytotoxin to combat invading pathogens
Authors: Prolo Carolina , Álvarez María Noel , Radi Rafael 
Published: November 2013

AbstractMacrophages are among the first cellular actors facing the invasion of microorganisms. These cells are able to internalize pathogens and destroy them by means of toxic mediators, many of which are produced enzymatically and have strong oxidizing capacity. Indeed, macrophages count on the NADPH oxidase complex activity, which is triggered during pathogen invasion and leads to the production of superoxide radical inside the phagosome. At the same time, the induction of nitric oxide synthase results in the production of nitric oxide in the cytosol which is able to readily diffuse to the phagocytic vacuole. Superoxide radical and nitric oxide react at diffusion controlled rates with each other inside the phagosome to yield peroxynitrite, a powerful oxidant capable to kill micro‐organisms. Peroxynitrite toxicity resides on oxidations and nitrations of biomolecules in the target cell. The central role of peroxynitrite as a key effector molecule in the control of infections has been proven in a wide number of models. However, some microorganisms and virulent strains adapt to survive inside the potentially hostile oxidizing microenvironment of the phagosome by either impeding peroxynitrite formation or rapidly detoxifying it once formed. In this context, the outcome of the infection process is a result of the interplay between the macrophage‐derived oxidizing cytotoxins such as peroxynitrite and the antioxidant defense machinery of the invading pathogens. © 2013 BioFactors, 40(2):215–225, 2014
Structural and binding properties of the PASTA domain of PonA2, a key penicillin binding protein from Mycobacterium tuberculosis
Authors: Calvanese Luisa , Falcigno Lucia , Maglione Cira , Marasco Daniela , Ruggiero Alessia , Squeglia Flavia , Berisio Rita , D'Auria Gabriella 
Published: November 2013

ABSTRACTPonA2 is one of the two class A penicillin binding proteins of Mycobacterium tuberculosis, the etiologic agent of tuberculosis. It plays a complex role in mycobacterial physiology and is spotted as a promising target for inhibitors. PonA2 is involved in adaptation of M. tuberculosis to dormancy, an ability which has been attributed to the presence in its sequence of a C‐terminal PASTA domain. Since PASTA modules are typically considered as β‐lactam antibiotic binding domains, we determined the solution structure of the PASTA domain from PonA2 and analyzed its binding properties versus a plethora of potential binders, including the β‐lactam antibiotics, two typical muropeptide mimics, and polymeric peptidoglycan. We show that, despite a high structural similarity with other PASTA domains, the PASTA domain of PonA2 displays different binding properties, as it is not able to bind muropeptides, or β‐lactams, or polymeric peptidoglycan. These results indicate that the role of PASTA domains cannot be generalized, as their specific binding properties strongly depend on surface residues, which are widely variable. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 712–719, 2014.
Model‐based derivation, analysis and control of unstable microaerobic steady‐states—Considering Rhodospirillum rubrum as an example
Authors: Carius Lisa , Rumschinski Philipp , Faulwasser Timm , Flockerzi Dietrich , Grammel Hartmut , Findeisen Rolf 
Published: November 2013

ABSTRACTMicroaerobic (oxygen‐limited) conditions are critical for inducing many important microbial processes in industrial or environmental applications. At very low oxygen concentrations, however, the process performance often suffers from technical limitations. Available dissolved oxygen measurement techniques are not sensitive enough and thus control techniques, that can reliable handle these conditions, are lacking. Recently, we proposed a microaerobic process control strategy, which overcomes these restrictions and allows to assess different degrees of oxygen limitation in bioreactor batch cultivations. Here, we focus on the design of a control strategy for the automation of oxygen‐limited continuous cultures using the microaerobic formation of photosynthetic membranes (PM) in Rhodospirillum rubrum as model phenomenon. We draw upon R. rubrum since the considered phenomenon depends on the optimal availability of mixed‐carbon sources, hence on boundary conditions which make the process performance challenging. Empirically assessing these specific microaerobic conditions is scarcely practicable as such a process reacts highly sensitive to changes in the substrate composition and the oxygen availability in the culture broth. Therefore, we propose a model‐based process control strategy which allows to stabilize steady‐states of cultures grown under these conditions. As designing the appropriate strategy requires a detailed knowledge of the system behavior, we begin by deriving and validating an unstructured process model. This model is used to optimize the experimental conditions, and identify properties of the system which are critical for process performance. The derived model facilitates the good process performance via the proposed optimal control strategy. In summary the presented model‐based control strategy allows to access and maintain microaerobic steady‐states of interest and to precisely and efficiently transfer the culture from one stable microaerobic steady‐state into another. Therefore, the presented approach is a valuable tool to study regulatory mechanisms of microaerobic phenomena in response to oxygen limitation alone. Biotechnol. Bioeng. 2014;111: 734–747. © 2013 Wiley Periodicals, Inc.
Lipase‐catalyzed process for biodiesel production: Protein engineering and lipase production
Authors: Hwang Hyun Tae , Qi Feng , Yuan Chongli , Zhao Xuebing , Ramkrishna Doraiswami , Liu Dehua , Varma Arvind 
Published: November 2013

AbstractBiodiesel is an environment‐friendly and renewable fuel produced by transesterification of various feedstocks. Although the lipase‐catalyzed biodiesel production has many advantages over the conventional alkali catalyzed process, its industrial applications have been limited by high‐cost and low‐stability of lipase enzymes. This review provides a general overview of the recent advances in lipase engineering, including both protein modification and production. Recent advances in biotechnology such as in protein engineering, recombinant methods and metabolic engineering have been employed but are yet to impact lipase engineering for cost‐effective production of biodiesel. A summary of the current challenges and perspectives for potential solutions are also provided. Biotechnol. Bioeng. 2014;111: 639–653. © 2013 Wiley Periodicals, Inc.
Early invasive versus selectively invasive strategy in patients with non‐ST‐segment elevation acute coronary syndrome: Impact of age
Authors: Angeli Fabio , Verdecchia Paolo , Savonitto Stefano , Morici Nuccia , De Servi Stefano , Cavallini Claudio 
Published: November 2013

BackgroundIt is unclear whether the benefits of an early invasive strategy (EIS) in patients with non‐ST‐segment elevation acute coronary syndromes (NSTEACS) equally apply to younger and older individuals. Elderly patients are generally less likely to undergo EIS when compared with younger patients.ObjectivesWe conducted a meta‐analysis to compare the benefit of an EIS versus a selectively invasive strategy (SIS) in patients with NSTEACS. We tested the hypothesis that the magnitude of benefit of an EIS over a SIS mainly applies to older individuals.MethodsWe extracted data from randomized controlled trials (RCTs) identified through search methodology filters. The primary outcome of the analysis was the composite of all‐cause death and myocardial infarction (MI). Secondary outcomes were death and MI taken alone and re‐hospitalization.ResultsNine trials (n = 9,400 patients) were eligible. The incidence of the composite end‐point of MI and all‐cause death was 16.0% with the EIS and 18.3% with the SIS (OR: 0.85, 95% CI: 0.76–0.95). The incidence of MI was 8.4% with the EIS and 10.9% with the SIS (OR: 0.75, 95% CI: 0.66–0.87). Similar results were obtained for rehospitalization (OR: 0.71, 95% CI: 0.55–0.90). The incidence of all‐cause death did not differ between the two groups. The EIS reduced the composite end‐point and re‐hospitalization to a greater extent in elderly than in younger patients (P for interaction = 0.044 and <0.0001, respectively). These findings were confirmed in meta‐regression analyses.ConclusionsIn patients with NSTEACS, a routine EIS reduces the risk of rehospitalization and the composite end point of recurrent MI and death to a greater extent in elderly than in younger individuals. © 2013 Wiley Periodicals, Inc.
Highly Sensitive and Selective Detection of Nitrophenolic Explosives by Using Nanospheres of a Tetraphenylethylene Macrocycle Displaying Aggregation‐Induced Emission
Authors: Feng Hai‐Tao , Zheng Yan‐Song 
Published: November 2013

AbstractA tetraphenylethylene (TPE) Schiff‐base macrocycle showing an aggregation‐induced emission (AIE) effect has been synthesized, which could aggregate into nanospheres and emit yellow fluorescence in aqueous media. By virtue of its AIE effect, the macrocycle showed a sensitive and selective response to 2,4,6‐trinitrophenol (TNP) and 2,4‐dinitrophenol (DNP) among a number of nitroaromatic compounds, which could be used to detect TNP and DNP at nanomolar levels. Moreover, it exhibited a superamplified quenching effect with DNP but not with TNP, providing a possible means of discriminating these two compounds. In comparison with open‐chain TPE Schiff‐bases, the cavity of the macrocycle is essential for the selectivity for DNP over TNP. In addition, quantitative analyses of both DNP and TNP in real water samples and qualitative detection of these two analytes in the solid state by the macrocycle have been tested. The reliability of the quantitative analysis has been confirmed by HPLC. Our findings demonstrate that the TPE Schiff‐base macrocycle has great potential as an excellent sensor for DNP and TNP.
Morphological Phase Diagram of Biocatalytically Active Ceria Nanostructures as a Function of Processing Variables and Their Properties
Authors: Sakthivel Tamilselvan , Das Soumen , Kumar Amit , Reid David L. , Gupta Ankur , Sayle Dean C. , Seal Sudipta 
Published: November 2013

AbstractInvited for this month’s cover is the group of Dr. Sudipta Seal from University of Central Florida, USA and a collaborator from the University of Kent, UK. The cover picture shows a morphological phase diagram of CeO2 indicating regions of nanoparticle nanorods and nanocube formation after certain time periods of hydrothermal treatment. Read the full text of the article at page 1446.
The Experience of Cognitive Impairment in People with Psychosis
Authors: Wood Helen , Cupitt Caroline , Lavender Tony 
Published: November 2013

Cognitive impairment has been widely studied in people with psychosis. However, research is lacking into the subjective experience of cognitive impairment, its impact and ways in which individuals cope. This study aimed to provide an account of the experience of cognitive impairment in people with a diagnosis of schizophrenia, including what difficulties people experience, how these difficulties are understood, how people respond to these difficulties and how they perceive others' views of these difficulties. A semi‐structured interview was carried out with eight participants with a diagnosis of schizophrenia focusing on participants' experiences of difficulties with cognitive functioning. Interpretative phenomenological analysis was used to analyse interview transcripts. Experience of cognitive impairment was understood in terms of six master themes: impaired controlled thinking, physical sensations and impaired movement, explanations for the impairment and comparisons to the past, managing the impairment, how others see the impairment and anticipating the future. This study is the first rigorous qualitative study of the subjective experience of cognitive impairment in people with psychosis, and it provides greater context for empirical findings. The results have significant implications for clinical psychology, including education about cognitive difficulties and the importance of cognitive functioning to formulation. New areas for research include coping strategies in relation to functioning and future perspectives, ascertaining staff understanding of cognitive impairment, and reflective conversation style as an intervention for metacognitive difficulties. Copyright © 2013 John Wiley & Sons, Ltd.Key Practitioner Message

Difficulties with cognitive functioning should be considered in clinical practitioners' formulations of clients' difficulties in the context of psychosis.
Services should consider providing service user and carer education about cognitive impairment in psychosis.
Staff may need further training in order to support people with psychosis who have difficulties with cognitive functioning.
Adaxial–abaxial polarity: The developmental basis of leaf shape diversity
Authors: Fukushima Kenji , Hasebe Mitsuyasu 
Published: November 2013

SummaryLeaves of flowering plants are diverse in shape. Part of this morphological diversity can be attributed to differences in spatiotemporal regulation of polarity in the upper (adaxial) and lower (abaxial) sides of developing leaves. In a leaf primordium, antagonistic interactions between polarity determinants specify the adaxial and abaxial domains in a mutually exclusive manner. The patterning of those domains is critical for leaf morphogenesis. In this review, we first summarize the gene networks regulating adaxial–abaxial polarity in conventional bifacial leaves and then discuss how patterning is modified in different leaf type categories. genesis 52:1–18, 2014. © 2013 The Authors. Genesis Published byWiley Periodicals, Inc.
Impaired neural drive in patients with low back pain
Authors: Chiou S.Y. , Shih Y.F. , Chou L.W. , McGregor A.H. , Strutton P.H. 
Published: November 2013

AbstractBackgroundControl of trunk movement relies on the integration between central neuronal circuits and peripheral skeletomuscular activities and it can be altered by pain. There is increasing evidence that there are deficits within the central nervous system controlling the trunk muscles in people with low back pain (LBP). However, it is unclear how LBP impacts upon neural drive to back muscles at different levels of voluntary contraction. Therefore, the purpose of this study was to investigate if neural drive is impaired in these patients.MethodsSeventeen patients with LBP and 11 healthy controls were recruited. Bilateral electromyographic (EMG) recordings were obtained from the erector spinae (ES) muscles at two vertebral levels (T12 and L4). Participants performed a series of brief isometric back extensions (50–100% maximum voluntary contraction – MVC), during which transcranial magnetic stimulation was delivered. The size of the evoked (superimposed) twitch was measured using dynamometry.ResultsThe size of the superimposed twitch decreased linearly with increasing contraction strength in the controls; however, this linear relationship was not observed in the patients. Additionally, patients had larger superimposed twitches and longer time‐to‐peak amplitudes during MVCs than those observed in controls. Furthermore, patients had lower MVC and root‐mean‐square EMG activity of ES muscles during MVCs.ConclusionsA decline of central neural drive to the back muscles at high level of voluntary contraction was observed in patients with LBP. These results suggest that it might be pertinent to include neuromuscular facilitation programmes and therapeutic exercise utilizing high voluntary contractions for patients with LBP.
Regulation of Hepatic Drug Transporter Activity and Expression by Organochlorine Pesticides
Authors: Bucher Simon , Le Vee Marc , Jouan Elodie , Fardel Olivier 
Published: November 2013

ABSTRACTOrganochlorine (OC) pesticides constitute a major class of persistent and toxic organic pollutants, known to modulate drug‐detoxifying enzymes. In the present study, OCs were demonstrated to also alter the activity and expression of human hepatic drug transporters. Activity of the sinusoidal influx transporter OCT1 (organic cation transporter 1) was thus inhibited by endosulfan, chlordane, heptachlor, lindane, and dieldrine, but not by dichlorodiphenyltrichloroethane isomers, whereas those of the canalicular efflux pumps MRP2 (multidrug resistance‐associated protein 2) and BCRP (breast cancer resistance protein) were blocked by endosulfan, chlordane, heptachlor, and chlordecone; this latter OC additionally inhibited the multidrug resistance gene 1 (MDR1)/P‐glycoprotein (P‐gp) activity. OCs, except endosulfan, were next found to induce MDR1/P‐gp and MRP2 mRNA expressions in hepatoma HepaRG cells; some of them also upregulated BCRP. By contrast, expression of sinusoidal transporters was not impaired (organic anion‐transporting polypeptide (OATP) 1B1 and OATP2B1) or was downregulated (sodium taurocholate co‐transporting polypeptide (NTCP) and OCT1). Such regulations of drug transporter activity and expression, depending on the respective nature of OCs and transporters, may contribute to the toxicity of OC pesticides.
Prenatal diagnosis of omphalopagus conjoined twins with shared megacystis
Authors: Bravo Coral , Sanjuan Cristina , Gámez Francisco , Pérez Ricardo , De León‐Luis Juan 
Published: November 2013

ABSTRACTConjoined twins are a very rare complication of monozygotic pregnancies, with thoraco‐omphalopagus twins being the most common presentation. Prenatal diagnosis of this anomaly can be achieved in the early first trimester. The areas of union between the embryos and the presence of associated malformations should be carefully evaluated for parent counseling. We report a case of omphalopagus conjoined twins with shared megacystis and discuss the ultrasound findings and management of these cases. © 2013 Wiley Periodicals, Inc. J Clin Ultrasound 42:360–362, 2014
Diagnosis of sirenomelia in the first trimester
Authors: Singh Chanchal , Lodha Pooja , Arora Deepshikha , Prabhu Sharma Akshatha , Kaul Anita 
Published: November 2013

ABSTRACTSirenomelia or “mermaid syndrome” is a rare congenital abnormality with an incidence of 1 in 60,000. We report a case diagnosed in the first trimester using two‐dimensional, three‐dimensional, and color Doppler ultrasound. With increasing emphasis on early diagnosis of fetal abnormalities, this case highlights the importance of looking for anomalies in the first trimester itself. In fact, the diagnosis of sirenomelia should be easier in the first trimester as severe oligohydramnios in later gestation hampers vision. © 2013 Wiley Periodicals, Inc. J Clin Ultrasound 42:355–359, 2014