bluuebunny/crossref_metadata_2025_split huggingface dataset:
Merging Sustainability with Organocatalysis in the Formation of Organic Carbonates by Using CO2 as a Feedstock
Authors: Whiteoak Christopher J. , Nova Ainara , Maseras Feliu , Kleij Arjan W. 
Published: September 2012

AbstractThe use of phenolic compounds as organocatalysts is discussed in the context of the atom‐efficient cycloaddition of carbon dioxide to epoxides, forming useful cyclic organic carbonate products. The presence and cooperative nature of adjacent phenolic groups in the catalyst structure results in significantly enhanced catalytic efficiencies, allowing these CO2 fixation reactions to operate efficiently under virtually ambient conditions. The cooperative effect has also been studied by computational methods. Furthermore, when the cycloaddition reactions are carried out on a larger scale and under solvent‐free conditions, further enhancements in activity are observed, combined with the advantageous requirement of reduced loadings of the binary organocatalyst system. The reported system is among one of the mildest and most effective metal‐free catalysts for this conversion and contributes to a much more sustainable development of organic carbonate production; this feature has not been the main focus of previous contributions in this area.
Ferritin as a novel reporter gene for photoacoustic molecular imaging
Authors: Ha Seung Han , Carson Andrew R. , Kim Kang 
Published: September 2012

AbstractReporter genes may serve as endogenous contrast agents in the field of photoacoustic (PA) molecular imaging (PMI), enabling greater characterization of detailed cellular processes and disease progression. To demonstrate the feasibility of using ferritin as a reporter gene, human melanoma SK‐24 (SK‐MEL‐24) cells were co‐transfected with plasmid expressing human heavy chain ferritin (H‐FT) and plasmid expressing enhanced green fluorescent protein (pEGFP‐C1) using lipofectamine™ 2000. Nontransfected SK‐MEL‐24 cells served as a negative control. Fluorescent imaging of GFP confirmed transfection and transgene expression in co‐transfected cells. To detect iron accumulation due to ferritin overexpression in SK‐MEL‐24 cells, a focused high‐frequency ultrasonic transducer (60 MHz, f/1.5), synchronized to a pulsed laser (fluence < 5 mJ/cm2) was used to scan the PA signal at a wide range NIR wavelengths (850–950 nm). PA signal intensity from H‐FT transfected SK‐MEL‐24 cells was about 5–9 dB higher than nontransfected SK‐MEL‐24 cells at 850–950 nm. Immunofluorescence and RT‐PCR analysis both indicate high levels of ferritin expression in H‐FT transfected SK‐MEL24 cells, with little ferritin expression in nontransfected SK‐MEL‐24 cells. In this study, the feasibility of using ferritin as a reporter gene for PMI has been demonstrated in vitro. The use of ferritin as a reporter gene represents a novel concept for PMI using an endogenous contrast agent and may provide various opportunities for molecular imaging and basic science research. © 2012 International Society for Advancement of Cytometry
Jelly belly trans‐synaptic signaling to anaplastic lymphoma kinase regulates neurotransmission strength and synapse architecture
Authors: Rohrbough Jeffrey , Kent Karla S. , Broadie Kendal , Weiss Joseph B. 
Published: September 2012

AbstractIn Drosophila, the secreted signaling molecule Jelly Belly (Jeb) activates anaplastic lymphoma kinase (Alk), a receptor tyrosine kinase, in multiple developmental and adult contexts. We have shown previously that Jeb and Alk are highly enriched at Drosophila synapses within the CNS neuropil and neuromuscular junction (NMJ) and postulated a conserved intercellular signaling function. At the embryonic and larval NMJ, Jeb is localized in the motor neuron presynaptic terminal whereas Alk is concentrated in the muscle postsynaptic domain surrounding boutons, consistent with anterograde trans‐synaptic signaling. Here, we show that neurotransmission is regulated by Jeb secretion by functional inhibition of Jeb–Alk signaling. Jeb is a novel negative regulator of neuromuscular transmission. Reduction or inhibition of Alk function results in enhanced synaptic transmission. Activation of Alk conversely inhibits synaptic transmission. Restoration of wild‐type postsynaptic Alk expression in Alk partial loss‐of‐function mutants rescues NMJ transmission phenotypes and confirms that postsynaptic Alk regulates NMJ transmission. The effects of impaired Alk signaling on neurotransmission are observed in the absence of associated changes in NMJ structure. Complete removal of Jeb in motor neurons, however, disrupts both presynaptic bouton architecture and postsynaptic differentiation. Nonphysiologic activation of Alk signaling also negatively regulates NMJ growth. Activation of Jeb–Alk signaling triggers the Ras‐MAP kinase cascade in both pre‐ and postsynaptic compartments. These novel roles for Jeb–Alk signaling in the modulation of synaptic function and structure have potential implications for recently reported Alk functions in human addiction, retention of spatial memory, cognitive dysfunction in neurofibromatosis, and pathogenesis of amyotrophic lateral sclerosis. © 2012 Wiley Periodicals, Inc. Develop Neurobiol, 2013
Mature proteins derived from Epstein–Barr virus fail to feed into the MHC class I antigenic pool
Authors: Fiebiger Benjamin M. , Moosmann Andreas , Behrends Uta , Mautner Josef 
Published: September 2012

The immediate presentation of peptide epitopes on MHC class I (MHC I) after antigen expression has led to the concept that MHC I ligands are mostly derived from defective ribosomal products (DRiPs), a subset of newly synthesized proteins that are rapidly degraded by the proteasome. Whether and to what extent mature proteins contribute to the antigenic pool, however, has remained elusive. Here, we developed a conditional antigen expression system that allows studying antigen presentation from mature proteins by inducing their rapid proteasomal degradation in the absence of further antigen synthesis. Target cells in which expression of two Epstein–Barr virus (EBV) antigens was induced were rapidly recognized by antigen‐specific CD8+ T cells in a time‐ and dosage‐dependent manner, demonstrating that antigen presentation was linked to antigen synthesis. By contrast, T cells failed to recognize target cells containing large amounts of mature protein even after induction of their rapid proteasomal degradation. Thus, the presentation of these antigens proved to be strictly dependent on protein synthesis whereas mature proteins failed to furnish the antigenic pool. These results have implications for the design of immunotherapeutic strategies that aim at targeting proteins with increased half‐lives and are hence overexpressed in tumors.
Sample preconcentration in open microchannels combined with MALDI‐MS
Authors: Mikkonen Saara , Rokhas Maria Khihon , Jacksén Johan , Emmer Åsa 
Published: September 2012

In this work, a method for preconcentrating samples in 1 cm long, 50–150 μm wide open microchannels is presented. Platinum electrodes were positioned at the channel ends, voltage was applied, and charged analyte was preconcentrated at the oppositely charged side during continuous supply of sample. The preconcentration was initially studied in a closed system, where an influence on the analyte position from a pH gradient, generated by water electrolysis, was observed. In the open channel, the analyte distribution after preconcentration was evaluated using MALDI‐MS with the channel as MALDI target. MALDI matrix was applied with an airbrush or by electrospray matrix deposition and by using the latter technique higher degrees of crystallization in the channels were obtained. After preconcentrating a 1 nM cytochrome c solution for 5 min, corresponding to a supplied amount of 1.25 fmol, a signal on the cathodic channel end could be detected. When a solution of cytochrome c trypsin digest was supplied, the peptides were preconcentrated at different positions along the channel depending on their charge.
Chemical and toxicological assessment of a full-scale biosolid compost
Authors: Patureau Dominique , Delgenes Nadine , Muller Mathieu , Dagnino Sonia , Lhoutellier Claire , Delgenes Jean-Philippe , Balaguer Patrick , Hernandez-Raquet Guillermina 
Published: September 2012

Abstract
The impact of a full-scale biosolid composting plant on the fate of a broad range of priority organic pollutants was investigated. Chemical analysis was performed at different steps of the process during two seasons. Simultaneously, the toxicological quality was assessed using estrogen α-, dioxin-, and pregnane X-receptor reporter cell lines. Mass-balance calculation highlighted the removal of easily degradable pollutants during composting. The important variations observed for each compound and for the two seasons might be explained by pollutant-fate dependency on process parameters like temperature. The final compost displayed low pregnane X activity but high estrogenic activity. The dioxin-like activity stayed constant through the process. The chemical and toxicological results highlight the importance of combining both approaches to accurately assess the compost quality. Such compilation of data on full-scale processes may be also very helpful for the environmental risk assessment of new organic waste disposal practices. Environ. Toxicol. Chem. 2012; 31: 2748–2756. © 2012 SETAC
Polyploidy road to therapy‐induced cellular senescence and escape
Authors: Wang Qin , Wu Peter C. , Dong David Z. , Ivanova Iana , Chu Elizabeth , Zeliadt Steven , Vesselle Hubert , Wu Daniel Y. 
Published: September 2012

AbstractTherapy‐induced cellular senescence (TCS), characterized by prolonged cell cycle arrest, is an in vivo response of human cancers to chemotherapy and radiation. Unfortunately, TCS is reversible for a subset of senescent cells, leading to cellular reproliferation and ultimately tumor progression. This invariable consequence of TCS recapitulates the clinical treatment experience of patients with advanced cancer. We report the findings of a clinicopathological study in patients with locally advanced non‐small cell lung cancer demonstrating that marker of in vivo TCS following neoadjuvant therapy prognosticate adverse clinical outcome. In our efforts to elucidate key molecular pathways underlying TCS and cell cycle escape, we have previously shown that the deregulation of mitotic kinase Cdk1 and its downstream effectors are important mediators of survival and cell cycle reentry. We now report that aberrant expression of Cdk1 interferes with apoptosis and promotes the formation of polyploid senescent cells during TCS. These polyploid senescent cells represent important transition states through which escape preferentially occurs. The Cdk1 pathway is in part modulated differentially by p21 and p27 two members of the KIP cyclin‐dependent kinase inhibitor family during TCS. Altogether, these studies underscore the importance of TCS in cancer therapeutics.
Inhibitors of vacuolar ATPase proton pumps inhibit human prostate cancer cell invasion and prostate‐specific antigen expression and secretion
Authors: Michel Vera , Licon‐Munoz Yamhilette , Trujillo Kristina , Bisoffi Marco , Parra Karlett J. 
Published: September 2012

AbstractVacuolar ATPases (V‐ATPases) comprise specialized and ubiquitously distributed pumps that acidify intracellular compartments and energize membranes. To gain new insights into the roles of V‐ATPases in prostate cancer (PCa), we studied the effects of inhibiting V‐ATPase pumps in androgen‐dependent (LNCaP) and androgen‐independent (C4‐2B) cells of a human PCa progression model. Treatment with nanomolar concentrations of the V‐ATPase inhibitors bafilomycin A or concanamycin A reduced the in vitro invasion in both cell types by 80%, regardless that V‐ATPase was prominent at the plasma membrane of C4‐2B cells and only traces were detected in the low‐metastatic LNCaP parental cells. In both cell types, intracellular V‐ATPase was excessive and co‐localized with prostate‐specific antigen (PSA) in the Golgi compartment. V‐ATPase inhibitors reversibly excluded PSA from the Golgi and led to the accumulation of largely dispersed PSA‐loaded vesicles of lysosomal composition. Inhibition of acridine orange staining and transferrin receptor recycling suggested defective endosomal and lysosomal acidification. The inhibitors, additionally, interfered with the AR‐PSA axis under conditions that reduced invasion. Bafilomycin A significantly reduced steady‐state and R1881‐induced PSA mRNA expression and secretion in the LNCaP cells which are androgen‐dependent, but not in the C4‐2B cells which are androgen ablation‐resistant. In the C4‐2B cells, an increased susceptibility to V‐ATPase inhibitors was detected after longer treatments, as proliferation was reduced and reversibility of bafilomycin‐induced responses impaired. These findings make V‐ATPases attractive targets against early and advanced PCa tumors.
Smoke‐induced microRNA and related proteome alterations. Modulation by chemopreventive agents
Authors: De Flora Silvio , Balansky Roumen , D'Agostini Francesco , Cartiglia Cristina , Longobardi Mariagrazia , Steele Vernon E. , Izzotti Alberto 
Published: September 2012

AbstractDysregulation of microRNAs (miRNAs) has important consequences on gene and protein expression since a single miRNA targets a number of genes simultaneously. This article provides a review of published data and ongoing studies regarding the effects of cigarette smoke (CS), either mainstream (MCS) or environmental (ECS), on the expression of miRNAs and related proteins. The results generated in mice, rats, and humans provided evidence that exposure to CS results in an intense dysregulation of miRNA expression in the respiratory tract, which is mainly oriented in the sense of downregulation. In parallel, there was an upregulation of proteins targeted by the downregulated miRNAs. These trends reflect an attempt to defend the respiratory tract by means of antioxidant mechanisms, detoxification of carcinogens, DNA repair, anti‐inflammatory pathways, apoptosis, etc. However, a long‐lasting exposure to CS causes irreversible miRNA alterations that activate carcinogenic mechanisms, such as modulation of oncogenes and oncosuppressor genes, cell proliferation, recruitment of undifferentiated stem cells, inflammation, inhibition of intercellular communications, angiogenesis, invasion, and metastasis. The miRNA alterations induced by CS in the lung of mice and rats are similar to those observed in the human respiratory tract. Since a number of miRNAs that are modulated by CS and/or chemopreventive agents are subjected to single nucleotide polymorphisms in humans, they can be evaluated according to toxicogenomic/pharmacogenomics approaches. A variety of cancer chemopreventive agents tested in our laboratory modulated both baseline and CS‐related miRNA and proteome alterations, thus contributing to evaluate both safety and efficacy of dietary and pharmacological agents.
Comparative Effectiveness of Low‐Molecular‐Weight Heparins versus Other Anticoagulants in Major Orthopedic Surgery: A Systematic Review and Meta‐analysis
Authors: Sobieraj Diana M. , Coleman Craig I. , Tongbram Vanita , Chen Wendy , Colby Jennifer , Lee Soyon , Kluger Jeffrey , Makanji Sagar , Ashaye Ajibade , White C. Michael 
Published: September 2012

Study ObjectiveTo evaluate the comparative efficacy and safety of low‐molecular‐weight heparins (LMWHs) versus other anticoagulants as venous thromboembolism prophylaxis in major orthopedic surgery.DesignSystematic review with meta‐analysis of 37 randomized controlled trials.PatientsPatients undergoing total hip replacement, total knee replacement, or hip fracture surgery who received prophylaxis with a LMWH or another anticoagulant.Measurements and Main ResultsWe conducted a systematic literature search of the MEDLINE, Cochrane Central Register of Controlled Trials, and Scopus databases (1980–July 2011) to identify randomized controlled trials. Trials were included if they directly compared LMWH prophylaxis with another anticoagulant class and reported outcomes of interest. Compared with patients who received unfractionated heparin (UFH), patients who received LMWHs had fewer pulmonary embolism, total deep vein thrombosis (DVT), major bleeding, and heparin‐induced thrombocytopenia events. Compared with patients who received vitamin K antagonists (VKAs), patients who received LMWHs had fewer total DVT and distal DVT events but reported increased major bleeding, minor bleeding, and surgical site bleeding events. Major efficacy end points such as symptomatic venous thromboembolism, pulmonary embolism, and nonfatal pulmonary embolism showed similar benefits of therapy with LMWHs and VKAs. Compared with patients receiving factor Xa inhibitors, patients who received LMWHs had more major venous thromboembolism, pulmonary embolism, total DVT, asymptomatic DVT, proximal DVT, and distal DVT events but fewer major bleeding events. Compared with patients receiving direct thrombin inhibitors (DTIs), patients who received LMWHs had more major venous thromboembolism, total DVT, and proximal DVT events without significantly negatively affecting bleeding. However, patients who received LMWHs had fewer distal DVT events versus those who received DTIs. Subgroup analyses indicated differences based on the surgical procedure and individual drug within certain pharmacologic classes.ConclusionAccording to moderate‐to‐high strength of evidence, LMWH prophylaxis provides additional benefits with less harm compared with UFH. With predominantly moderate strength of evidence, the balance of benefits to harms for factor Xa inhibitors or DTIs compared with LMWHs seems favorable. With predominantly low‐to‐moderate strength of evidence, the known benefits in total DVT and distal DVT with LMWHs versus VKAs may not be sufficient to counteract the increased risk of bleeding.
Effect of the Clopidogrel–Proton Pump Inhibitor Drug Interaction on Adverse Cardiovascular Events in Patients with Acute Coronary Syndrome
Authors: Bhurke Sharvari M. , Martin Bradley C. , Li Chenghui , Franks Amy M. , Bursac Zoran , Said Qayyim 
Published: September 2012

Study ObjectiveTo examine the effect of the drug interaction between clopidogrel and proton pump inhibitors (PPIs) on the risk of an adverse cardiovascular event.DesignPopulation‐based, retrospective cohort study.Data SourceIMS LifeLink Health Plan administrative claims database.PatientsA total of 10,101 patients aged 18 years or older with a diagnosis of acute coronary syndrome (ACS) made during a hospitalization or emergency department visit between 2001 and 2008 and who had their first clopidogrel prescription within 90 days after their ACS diagnosis were included in the study. Patients were stratified according to concurrent use (clopidogrel plus PPI group) or no use (clopidogrel alone group) of the following PPIs: esomeprazole, lansoprazole, omeprazole, pantoprazole, or rabeprazole.Measurements and Main ResultsData were collected on baseline patient demographic and clinical characteristics. Patients were followed from their first clopidogrel prescription until they experienced an adverse cardiovascular event, defined as inpatient hospitalization or emergency department visits for myocardial infarction, percutaneous coronary intervention, or intermediate coronary syndrome; were disenrolled; discontinued clopidogrel; or reached the end of the study period. Using a propensity scoring method, the clopidogrel plus PPI group was matched in a 1:1 ratio with the clopidogrel alone group. Exposure to overlapping clopidogrel‐PPI prescriptions was modeled as a time‐dependent covariate. The Cox hazards regression model was used to estimate the risk of an adverse cardiovascular event in the clopidogrel plus PPI group versus the clopidogrel alone group. Propensity score matching resulted in 2674 patient pairs. In the propensity score–matched sample, the mean age was 61.30 years, with a mean follow‐up of 268 days, and 70.04% were male. Concurrent use of clopidogrel with a PPI was associated with a significantly increased risk of a cardiovascular adverse event (hazard ratio 1.438, 95% confidence interval 1.237–1.671) compared with clopidogrel alone.ConclusionConcurrent use of clopidogrel plus a PPI was associated with a significant increase in risk of an adverse cardiovascular event in patients with ACS. Large randomized studies are needed to confirm this finding. Until then, clinicians should prescribe the concurrent use of these two drugs cautiously.
Outcomes from a Mentored Research Boot Camp: Focused Investigator Training (FIT) Program
Authors: Marinac Jacqueline S. , Gerkovich Mary M. 
Published: September 2012

Study ObjectiveTo evaluate the change in mentee self‐efficacy with regard to research, number of grant submissions, and total amount of new monies awarded to graduates of a novel, mentored, investigator‐training program—the Focused Investigator Training (FIT) Program.DesignRetrospective observational analysis.SettingAmerican College of Clinical Pharmacy Research Institute.ParticipantsFifty‐five mentees from the 2008, 2009, 2010, and 2011 FIT Programs.InterventionThe FIT Program is a novel, intensive, 5‐day, mentored development “boot camp” for mid‐career investigators holding research‐intensive positions. The program consists of proposal groups of two mentors and two–four mentees, one‐on‐one office hours, lectures, panel discussions, directed readings, and small group sessions. Twelve highly successful researchers and biostatisticians were recruited as mentors. Mentees submitted a detailed proposal and received faculty feedback before the program.Measurements and Main ResultsThe main outcomes of the FIT Program were mentee self‐efficacy with regard to research, number of grant submissions, and total amount of new monies awarded to 2008 and 2009 FIT Program graduates. Univariate statistical analysis was conducted to determine characteristics of those FIT attendees with subsequent successful grantsmanship. A combined measure of self‐confidence in successful grantsmanship was significantly increased after completion of the FIT program. More than $2.7 million was funded to FIT graduates as principal investigators, and as coinvestigators or subcontractors, an additional $382,000 was awarded in new funds. Seven mentees from the 2008 and 2009 classes received new federal funding, mostly through various K‐type award mechanisms.ConclusionThe FIT Program was associated with a significant increase in attendees' self‐efficacy for obtaining external research funding. Program attendance was associated with numerous successfully funded grants by pharmacist investigators. Future FIT Program success hinges on attracting adequate numbers of qualified applicants.