bluuebunny/crossref_metadata_2025_split huggingface dataset:
An ionic–chemical–mechanical model for muscle contraction
Authors: Manning Gerald S. 
Published: September 2016

AbstractThe dynamic process underlying muscle contraction is the parallel sliding of thin actin filaments along an immobile thick myosin fiber powered by oar‐like movements of protruding myosin cross bridges (myosin heads). The free energy for functioning of the myosin nanomotor comes from the hydrolysis of ATP bound to the myosin heads. The unit step of translational movement is based on a mechanical‐chemical cycle involving ATP binding to myosin, hydrolysis of the bound ATP with ultimate release of the hydrolysis products, stress‐generating conformational changes in the myosin cross bridge, and relief of built‐up stress in the myosin power stroke. The cycle is regulated by a transition between weak and strong actin–myosin binding affinities. The dissociation of the weakly bound complex by addition of salt indicates the electrostatic basis for the weak affinity, while structural studies demonstrate that electrostatic interactions among negatively charged amino acid residues of actin and positively charged residues of myosin are involved in the strong binding interface. We therefore conjecture that intermediate states of increasing actin–myosin engagement during the weak‐to‐strong binding transition also involve electrostatic interactions. Methods of polymer solution physics have shown that the thin actin filament can be regarded in some of its aspects as a net negatively charged polyelectrolyte. Here we employ polyelectrolyte theory to suggest how actin–myosin electrostatic interactions might be of significance in the intermediate stages of binding, ensuring an engaged power stroke of the myosin motor that transmits force to the actin filament, and preventing the motor from getting stuck in a metastable pre‐power stroke state. We provide electrostatic force estimates that are in the pN range known to operate in the cycle.
Dabigatran antagonizes growth, cell‐cycle progression, migration, and endothelial tube formation induced by thrombin in breast and glioblastoma cell lines
Authors: Vianello Fabrizio , Sambado Luisa , Goss Ashley , Fabris Fabrizio , Prandoni Paolo 
Published: September 2016

AbstractThrombin activates its G‐coupled seven transmembrane protease‐activated receptor (PAR‐1) by cleaving the receptor's N‐terminal end. In several human cancers, PAR1 expression and activation correlates with tumor progression and metastatization. This provides compelling evidence for the effectiveness of an appropriate antithrombin agent for the adjuvant treatment of patients with cancer. Dabigatran is a selective direct thrombin inhibitor that reversibly binds to thrombin. In this study, we aimed to explore if dabigatran may affect mechanisms favoring tumor growth by interfering with thrombin‐induced PAR‐1 activation.We confirmed that exposure of tumor cells to thrombin significantly increased cell proliferation and this was coupled with downregulation of p27 and concomitant induction of cyclin D1. Dabigatran was consistently effective in antagonizing thrombin‐induced proliferation as well as it restored the baseline pattern of cell cycle protein expression. Thrombin significantly upregulated the expression of proangiogenetic proteins like Twist and GRO‐α in human umbilical vascular endothelial cells (HUVEC) cells and their expression was significantly brought down to control levels when dabigatran was added to culture. We also found that the chemoattractant effect of thrombin on tumor cells was lost in the presence of dabigatran, and that the thrombin antagonist was effective in dampening vascular tube formation induced by thrombin. Our data support a role of thrombin in inducing the proliferation, migration, and proangiogenetic effects of tumor cells in vitro. Dabigatran has activity in antagonizing all these effects, thereby impairing tumor growth and progression. In vivo models may help to understand the relevance of this pathway.
Chemodiversity Associated with Cytotoxicity and Antimicrobial Activity ofPiper aduncumvar.ossanum
Authors: Gutiérrez Yamilet , Montes Rodny , Scull Ramón , Sánchez Arturo , Cos Paul , Monzote Lianet , Setzer William N. 
Published: September 2016

Chemical analysis, antimicrobial activity and cytotoxic effects of essential oils (EOs) from leaves ofPiper aduncumvar.ossanumfrom two localities Bauta (EO‐B) and Ceiba (EO‐C), Artemisa Province, Cuba, were determined.EOs were obtained by hydrodistillation and analyzed by gas chromatography/mass spectrometry.EO‐B demonstrated higher activity againstS. aureusandL. amazonensis; while a lower cytotoxicity on mammalian cells was observed. BothEOs displayed the same activity againstPlasmodium falciparum,Trypanosoma cruzi,Trypanosoma brucei, andLeishmania infantum. BothEOs were inactive againstEscherichia coliandCandida albicans.
Importance of a Conserved Lys/Arg Residue for Ligand/PDZ Domain Interactions as Examined by Protein Semisynthesis
Authors: Pedersen Søren W. , Moran Griffin E. , Sereikaitė Vita , Haugaard‐Kedström Linda M. , Strømgaard Kristian 
Published: September 2016

AbstractPDZ domains are ubiquitous small protein domains that are mediators of numerous protein–protein interactions, and play a pivotal role in protein trafficking, synaptic transmission, and the assembly of signaling‐transduction complexes. In recent years, PDZ domains have emerged as novel and exciting drug targets for diseases (in the brain in particular), so understanding the molecular details of PDZ domain interactions is of fundamental importance. PDZ domains bind to a protein partner at either a C‐terminal peptide or internal peptide motifs. Here, we examined the importance of a conserved Lys/Arg residue in the ligand‐binding site of the second PDZ domain of PSD‐95, by employing a semisynthetic approach. We generated six semisynthetic PDZ domains comprising different proteogenic and nonproteogenic amino acids representing subtle changes of the conserved Lys/Arg residue. These were tested with four peptide interaction partners, representing the two different binding modes. The results highlight the role of a positively charged amino acid in the β1–β2 loop of PDZ domains, and show subtle differences for canonical and noncanonical interaction partners, thus providing additional insight into the mechanism of PDZ/ligand interaction.
MiR‐21 inhibitor suppressed the progression of retinoblastoma via the modulation of PTEN/PI3K/AKT pathway
Authors: Gui Fu , Hong Zhengdong , You Zhipeng , Wu Hongxi , Zhang Yulan 
Published: September 2016

AbstractMicroRNA‐21 (miR‐21) was reported to act as an oncogene during the development of many human tumors. However, little was revealed about the function of miR‐21 in retinoblastoma (RB). In this study, we examined the expression of miR‐21 in RB tissues and explored the relationship between miR‐21 and phosphatase and tensin homolog (PTEN)/phosphatidylinositol‐3‐OH kinase (PI3K)/AKT signal. Quantitative real‐time PCR (qRT‐PCR) results showed that the level of miR‐21 in RB tissues was higher than that in retinal normal tissues. In Weri‐Rb‐1 cells, miR‐21 inhibitor suppressed the expression of miR‐21 and cell viability, but improved cell apoptotic rates by modulating the levels of PDCD4, Bax, and Bcl‐2. Meanwhile, miR‐21 inhibitor suppressed cell migration and invasion via inhibiting the protein levels of MMP2 and MMP9 and significantly affected the expression of PTEN, PI3K, and p‐AKT. Taken together, miR‐21 inhibitor suppressed cell proliferation, migration, and invasion via the PTEN/PI3K/AKT signal. These findings revealed the molecular basis of miR‐21 functioning in the progression of RB and provided a new means for cell therapy in RB.
Zeolite Beta Formation from Clear Sols: Silicate Speciation, Particle Formation and Crystallization Monitored by Complementary Analysis Methods
Authors: Castro Maria , Haouas Mohamed , Lim Ivy , Bongard Hans J. , Schüth Ferdi , Taulelle Francis , Karlsson Gunnel , Alfredsson Viveka , Breyneart Eric , Kirschhock Christine E. A. , Schmidt Wolfgang 
Published: September 2016

AbstractThe formation of silicate nanoaggregates (NAs) at the very early stages of precursor sols and zeolite beta crystallization from silicate nanoparticles (NPs) are investigated in detail using a combination of different analysis methods, including liquid‐state 29Si, 27Al, 14N, and 1H NMR spectroscopy, mass spectrometry (MS), small‐angle X‐ray scattering (SAXS), X‐ray diffraction (XRD), and transmission electron microscopy at cryogenic temperatures (cryo‐TEM). Prior to hydrothermal treatment, silicate NAs are observed if the Si/OH ratio in the reaction mixture is greater than 1. Condensation of oligomers within the NAs then generates NPs. Aluminum doped into the synthesis mixtures is located exclusively in the NPs, and is found exclusively in a state that is fourfold connected to silicate, favoring their condensation and aggregation. These results are in agreement with general trends observed for other systems. Silicate NAs are essential intermediates for zeolite formation and are generated by the aggregation of hydrated oligomers, aluminate, and templating cations. Subsequent further intra‐nanoaggregate silicate condensation results in the formation of NPs. 1H and 14N liquid NMR as well as diffusion ordered spectroscopy (DOSY) experiments provide evidence for weakly restricted rotational and translational mobility of the organic template within NAs as a consequence of specific silicate–template interactions. NAs thus appear as key species in clear sols, and their presence in the precursor sol favors silicate condensation and further crystallization, promoted either by increasing the Si/OH ratio or by heating.
Asymmetric Diels–Alder Reaction of α‐Substituted and β,β‐Disubstituted α,β‐Enals via Diarylprolinol Silyl Ether for the Construction of All‐Carbon Quaternary Stereocenters
Authors: Hayashi Yujiro , Bondzic Bojan P. , Yamazaki Tatsuya , Gupta Yogesh , Ogasawara Shin , Taniguchi Tohru , Monde Kenji 
Published: September 2016

AbstractThe asymmetric Diels–Alder reaction of α‐substituted acrolein proceeds in the presence of the trifluoroacetic acid salt of trifluoromethyl‐substituted diarylprolinol silyl ether to afford the exo‐isomer with both excellent diastereoselectivity and high enantioselectivity. In the Diels–Alder reaction of a β,β‐disubstituted α,β‐unsaturated aldehyde, good exo‐selectivity and excellent enantioselectivity was obtained when the perchloric acid salt of the bulky triisopropyl silyl ether of trifluoromethyl substituted diarylprolinol was employed as an organocatalyst in the presence of water. In both cases, all‐carbon quaternary stereocenters are constructed enantioselectively.
Characterization of G‐Quadruplex/Hairpin Transitions of RNAs by 19F NMR Spectroscopy
Authors: Granqvist Lotta , Virta Pasi 
Published: September 2016

Abstract2′‐O‐[(4‐Trifluoromethyl‐triazol‐1‐yl)methyl] reporter groups have been incorporated into guanosine‐rich RNA models (including a known bistable Qd/Hp RNA and two G‐rich regions of mRNA of human prion protein, PrP) and applied for the 19F NMR spectroscopic characterization of plausible G‐quadruplex/hairpin (Qd/Hp) transitions in these RNA structures. For the synthesis of the CF3‐labeled RNAs, phosphoramidite building blocks of 2′‐O‐[(4‐CF3‐triazol‐1‐yl)methyl] nucleosides (cytidine, adenosine, and guanosine) were prepared and used as an integral part of the standard solid‐phase RNA synthesis. The obtained 19F NMR spectra supported the usual characterization data (obtained by UV‐ and CD‐melting profiles and by 1H NMR spectra of the imino regions) and additionally gave more detailed information on the Qd/Hp transitions. The molar fractions of the secondary structural species (Qd, Hp) upon thermal denaturation and under varying ionic conditions could be determined from the intensities and shifts of the 19F NMR signals. For a well‐behaved Qd/Hp transition, thermodynamic parameters could be extracted.
Differential impact of minimal residual disease negativity according to the salvage status in patients with relapsed/refractory B‐cell acute lymphoblastic leukemia
Authors: Jabbour Elias , Short Nicholas J. , Jorgensen Jeffrey L. , Yilmaz Musa , Ravandi Farhad , Wang Sa A. , Thomas Deborah A. , Khoury Joseph , Champlin Richard E. , Khouri Issa , Kebriaei Partow , O'Brien Susan M. , Garcia‐Manero Guillermo , Cortes Jorge E. , Sasaki Koji , Dinardo Courtney D. , Kadia Tapan M. , Jain Nitin , Konopleva Marina , Garris Rebecca , Kantarjian Hagop M. 
Published: September 2016

BACKGROUNDMinimal residual disease (MRD) assessment predicts survival for patients with newly diagnosed acute lymphoblastic leukemia (ALL). Its significance in relapsed/refractory ALL is less clear.METHODSThis study identified 78 patients with relapsed/refractory B‐cell ALL who achieved a morphologic response with inotuzumab ozogamicin (n = 41), blinatumomab (n = 11), or mini‐hyperfractionated cyclophosphamide, vincristine, and doxorubicin plus inotuzumab (n = 26) during either salvage 1 (S1; n = 46) or salvage 2 (S2; n = 32) and had undergone an MRD assessment by multiparameter flow cytometry at the time of remission.RESULTSMRD negativity was achieved in 41 patients overall (53%). The MRD negativity rate was 57% in S1 and 47% in S2. Among patients in S1, achieving MRD negativity was associated with longer event‐free survival (EFS; median, 18 vs 7 months; 2‐year EFS rate, 46% vs 17%; P = .06) and overall survival (OS; median, 27 vs 9 months; 2‐year OS, 52% vs 36%; P = .15). EFS and OS were similar in S2, regardless of the MRD response. Among MRD‐negative patients who underwent allogeneic stem cell transplantation (SCT), EFS and OS were superior for those who underwent SCT in S1 rather than S2 (P = .003 and P = .04, respectively). Patients in S1 who achieved MRD negativity and subsequently underwent SCT had the best outcomes with a 2‐year OS rate of 65%.CONCLUSIONSPatients with relapsed/refractory ALL who achieve MRD negativity in S1 can have long‐term survival. Patients in S2 generally have poor outcomes, regardless of their MRD status. Cancer 2017;123:294–302. © 2016 American Cancer Society.
A multicenter, single‐arm, open‐label, phase 2 study of apitolisib (GDC‐0980) for the treatment of recurrent or persistent endometrial carcinoma (MAGGIE study)
Authors: Makker Vicky , Recio Fernando O. , Ma Ling , Matulonis Ursula A. , Lauchle Jennifer O. , Parmar Hema , Gilbert Houston N. , Ware Joseph A. , Zhu Rui , Lu Shan , Huw Ling‐Yuh , Wang Yulei , Koeppen Hartmut , Spoerke Jill M. , Lackner Mark R. , Aghajanian Carol A. 
Published: September 2016

BACKGROUNDThe current single‐arm, open‐label trial was designed to evaluate the activity of apitolisib (GDC‐0980), a dual phosphoinositide 3‐kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor, in patients with advanced endometrial cancer (EC).METHODSPatients with recurrent or persistent EC who were treated with 1 to 2 prior lines of chemotherapy but no prior PI3K/mTOR inhibitor received oral apitolisib at a dose of 40 mg daily during 28‐day cycles until disease progression or intolerable toxicity occurred. Patients with type I/II diabetes who required insulin were excluded. The primary endpoints were progression‐free survival (PFS) at 6 months and objective response rate.RESULTSA total of 56 women were enrolled, including 13 (23%) with well‐controlled diabetes. Reasons for discontinuation were disease progression (24 patients; 43%), adverse events (13 patients; 23%), and withdrawal by subject (12 patients; 21%). Grade 3/4 apitolisib‐related adverse events were hyperglycemia (46%), rash (30%), colitis (5%), and pneumonitis (4%) (toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). The PFS rate at 6 months was 20% (Kaplan‐Meier estimate; 95% confidence interval [95% CI], 7%‐33%). The objective response rate was 6% (confirmed). The median PFS was 3.5 months (95% CI, 2.7‐3.7 months) and the median overall survival was 15.7 months (95% CI, 9.2‐17.0 months). Nineteen patients discontinued the study before the first tumor assessment. Dose reductions were required for 4 diabetic (31%) and 18 nondiabetic (42%) patients. Comprehensive molecular profiling of 46 evaluable archival tumor samples demonstrated that 57% of patients had at least 1 alteration in phosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit alpha (PIK3CA), phosphatase and tensin homolog (PTEN), or AKT1. All 3 patients with a confirmed response had at least 1 alteration in a PI3K pathway gene.CONCLUSIONSThe antitumor activity noted with the use of a dose of 40 mg of apitolisib daily was limited by tolerability, especially in diabetic patients. Patients with PI3K pathway mutations may have derived enhanced benefit from apitolisib. Cancer 2016;122:3519–28. © 2016 American Cancer Society.
Patterns and predictors of colorectal cancer care coordination: A population‐based survey of Australian patients
Authors: Durcinoska Ivana , Young Jane M. , Solomon Michael J. 
Published: September 2016

BACKGROUNDImproving care coordination is a key priority for health services. The aims of this study were to identify patient‐ and health service–related predictors of poorly coordinated care and to explore patient preferences to assist care coordination.METHODSPatients with incident colorectal cancer, identified from a state‐wide cancer registry, completed a self‐report questionnaire 6 to 8 months after their diagnosis. Care coordination was assessed with the Cancer Care Coordination Questionnaire for Patients. Multiple linear regression models were used to predict factors associated with a poor experience with cancer care coordination.RESULTSAmong 560 patients (56% response rate), care coordination experiences were normally distributed (mean score, 76.1; standard deviation, 10.9). Patients who had 3 or more comorbid conditions (β, –4.56; standard error [SE], 1.46; P = .006), little or no understanding of the health system (β, –4.34; SE, 0.94; P < .001), and no regular general practitioner (GP; β, –4.09; SE, 2.07; P = .049) experienced poorer care coordination. At the health service level, patients who did not receive a written pretreatment plan (β, –4.15; SE, 0.95; P < .001) or did not see a cancer care coordinator (β, –3.29; SE, 1.03; P = .001) had lower scores. The most preferred resources included information packs (92%), written care plans (88%), and improved access to their own personal medical records (electronic, 86; paper, 84%), with most patients preferring a shared GP and surgeon care model.CONCLUSIONSThere was wide variation in experiences across the state. The factors associated with lower scores provide a focus for targeted strategies for improving patients' experience with colorectal cancer care coordination. Cancer 2017;123:319–326. © 2016 American Cancer Society.
DIANA‐TarBase and DIANA Suite Tools: Studying Experimentally Supported microRNA Targets
Authors: Paraskevopoulou Maria D. , Vlachos Ioannis S. , Hatzigeorgiou Artemis G. 
Published: September 2016

AbstractmicroRNAs (miRNAs) are short non‐coding RNAs (∼22 nts) present in animals, plants, and viruses. They are considered central post‐transcriptional regulators of gene expression and are key components in a great number of physiological and pathological conditions. The accurate characterization of their targets is considered essential to a series of applications and basic or applied research settings. DIANA‐TarBase (http://www.microrna.gr/tarbase) was initially launched in 2006. It is a reference repository indexing experimentally derived miRNA‐gene interactions in different cell types, tissues, and conditions across numerous species. This unit focuses on the study of experimentally supported miRNA‐gene interactions, as well as their functional interpretation through the use of available tools in the DIANA suite (http://www.microrna.gr). The proposed use‐case scenarios are presented in protocols, describing how to utilize the DIANA‐TarBase database and DIANA‐microT‐CDS server and perform miRNA‐targeted pathway analysis with DIANA‐miRPath‐v3. All analyses are directly invoked or initiated from DIANA‐TarBase. © 2016 by John Wiley & Sons, Inc.
Tempest: Accelerated MS/MS Database Search Software for Heterogeneous Computing Platforms
Authors: Adamo Mark E. , Gerber Scott A. 
Published: September 2016

AbstractMS/MS database search algorithms derive a set of candidate peptide sequences from in silico digest of a protein sequence database, and compute theoretical fragmentation patterns to match these candidates against observed MS/MS spectra. The original Tempest publication described these operations mapped to a CPU‐GPU model, in which the CPU (central processing unit) generates peptide candidates that are asynchronously sent to a discrete GPU (graphics processing unit) to be scored against experimental spectra in parallel. The current version of Tempest expands this model, incorporating OpenCL to offer seamless parallelization across multicore CPUs, GPUs, integrated graphics chips, and general‐purpose coprocessors. Three protocols describe how to configure and run a Tempest search, including discussion of how to leverage Tempest's unique feature set to produce optimal results. © 2016 by John Wiley & Sons, Inc.
Film Grain‐Size Related Long‐Term Stability of Inverted Perovskite Solar Cells
Authors: Chiang Chien‐Hung , Wu Chun‐Guey 
Published: September 2016

AbstractThe power conversion efficiency (PCE) of the perovskite solar cell is high enough to be commercially viable. The next important issue is the stability of the device. This article discusses the effect of the perovskite grain‐size on the long‐term stability of inverted perovskite solar cells. Perovskite films composed of various sizes of grains were prepared by controlling the solvent annealing time. The grain‐size related stability of the inverted cells was investigated both in ambient atmosphere at relative humidity of approximately 30–40 % and in a nitrogen filled glove box (H2O<0.1 ppm, O2<10 ppm). The PCE of the solar cell based on a perovskite film having the grain size larger than 1 μm (D‐10) decreases less than 10 % with storage in a glove box and less than 15 % when it was stored under an ambient atmosphere for 30 days. However, the cell using the perovskite film composed of small (∼100 nm) perovskite grains (D‐0) exhibits complete loss of PCE after storage under the ambient atmosphere for only 15 days and a PCE loss of up to 70 % with storage in the glove box for 30 days. These results suggest that, even under H2O‐free conditions, the chemical‐ and thermal‐induced production of pin holes at the grain boundaries of the perovskite film could be the reason for long‐term instability of inverted perovskite solar cells.