bluuebunny/crossref_metadata_2025_split huggingface dataset:
DIAMETRIC GROWTH AND PROPERTIES OF Copaifera langsdorffii DESF. BY SECOND CUTTING CYCLE
Authors: Do Carmo Jair Figueiredo , Latorraca João Vicente De Figueiredo , Santos Glaycianne Christine Vieira dos , Carmo Fábio Henrique Della Justina do , Miranda Dirceu Lúcio Carneiro de , Lousada José Luis Penetra Cerveira 
Published: June 2018

The aim of this study was to analyze forest management effects in the diametric growth and wood anatomical, chemical and physical properties of Copaifera langsdorffii trees, in an Ombrophilous Open Forest (state of Mato Grosso, Brazil). The forest management effects were determined through a comparative study between the wood properties of 10 years before and 10 years after the first logging, in 1987. Multivariate associations among the anatomical characteristics, macro and micronutrient, wood density, and current annual increment (ICA) were evaluated to every growth period through the two steps cluster analysis. The results indicated that the following characteristics were relevant to distinct the periods studied: ICA, vessel frequency, and wood density. C. langsdorffii respond to stimuli caused by forest management, adapting to the increase of resources availability, due to the opening gaps, and showing growth increase with reduction of wood density, which may indicate variations on the wood properties.
De participatiemythe; een drieluik over dubieuze beleidsassumpties
Authors: Trommel Willem 
Published: June 2018

The myth of participation; a triptych on dubious policy assumptions
This article argues that the politics of participation, as it is currently implemented in Dutch society, departs from dubious policy assumptions. The main problems relate to a controversial idea of what societal resilience is about, which in turn is a side-effect of the neoliberal conception of man and society. In particular three policy assumptions seem contested, regarding respectively the self-governance norm, the required levels of trust, and the presence of a ‘loving culture’. While discussing these three topics, the article also introduces three contributions to this special issue, which will focus in more detail on the poverty of the assumptions underlying the participation paradigm.
A novel thymidylate synthase from theVibrionales,Alteromonadales,Aeromonadales, andPasteurellales(VAAP) clade with altered nucleotide and folate binding sites
Authors: Lopez-Zavala Alonso A. , Guevara-Hernandez Eduardo , Vazquez-Lujan Luz H. , Sanchez-Paz Arturo , Garcia-Orozco Karina D. , Contreras-Vergara Carmen A. , Lopez-Leal Gamaliel , Arvizu-Flores Aldo A. , Ochoa-Leyva Adrian , Sotelo-Mundo Rogerio R. 
Published: June 2018

Thymidylate synthase (TS, E.C. 2.1.1.45) is a crucial enzyme forde novodeoxythymidine monophosphate (dTMP) biosynthesis. The gene for this enzyme isthyA, which encodes the folate-dependent TS that converts deoxyuridine monophosphate group (dUMP) into (dTMP) using the cofactor 5,10-methylenetetrahydrofolate (mTHF) as a carbon donor. We identified thethyAgene in the genome of theVibrio parahaemolyticusstrain FIM-S1708+ that is innocuous to humans but pathogenic to crustaceans. Surprisingly, we found changes in the residues that bind the substrate dUMP and mTHF, previously postulated as invariant among all TSs known (Finer-Moore, Santi & Stroud, 2003). Interestingly, those amino acid changes were also found in a clade of microorganisms that containsVibrionales,Alteromonadales,Aeromonadales, andPasteurellales(VAAP) from theGammaproteobacteriaclass. In this work, we studied the biochemical properties of recombinant TS fromV. parahemolyticusFIM-S1708+ (VpTS) to address the natural changes in the TS amino acid sequence of the VAAP clade. Interestingly, theKmfor dUMP was 27.3 ± 4.3 µM, about one-fold larger compared to other TSs. TheKmfor mTHF was 96.3 ± 18 µM, about three- to five-fold larger compared to other species, suggesting also loss of affinity. Thus, the catalytic efficiency was between one or two orders of magnitude smaller for both substrates. We used trimethoprim, a common antibiotic that targets both TS and DHFR for inhibition studies. The IC50values obtained were high compared to other results in the literature. Nonetheless, this molecule could be a lead for the design antibiotics towards pathogens from the VAAP clade. Overall, the experimental results also suggest that in the VAAP clade the nucleotide salvage pathway is important and should be investigated, since thede novodTMP synthesis appears to be compromised by a less efficient thymidylate synthase.
Examining the “July effect” on patients undergoing pituitary surgery
Authors: Bashjawish Bassel , Patel Shreya , Kılıç Suat , Hsueh Wayne D. , Liu James K. , Baredes Soly , Eloy Jean Anderson 
Published: June 2018

BackgroundOur aim in this study was to assess the impact of the turnover of residents in July on patients undergoing pituitary surgery.MethodsThis work was a retrospective cohort study of cases from the National Inpatient Sample (NIS). Patients who underwent pituitary surgery from 2005 to 2012 were selected in the NIS. Patients undergoing surgery in July and in non‐July months were compared to determine differences in demographics, comorbidities, and complications.ResultsOf the 12,939 patients, 1098 (8.5%) underwent pituitary surgery in July. Patients receiving surgery in July had similar demographics and Agency for Healthcare Research and Quality comorbidity values compared with patients receiving surgery in other months. There were no significant differences in mortality, cerebral edema, cerebrospinal fluid leakage, iatrogenic pituitary complications, iatrogenic cerebrovascular accidents, urinary tract infections, pulmonary edema, pulmonary complications, or acute cardiac complications. There were no differences in the rate of postoperative fistulas, hematomas, perforations, or infections. The use of meningeal suturing, pedicled or free‐flap reconstruction, and skin reconstruction was more frequent in July. Finally, hospitalization costs in July were similar to costs in other months.ConclusionThe turnover of new residents in July showed no change in complication rates for patients undergoing pituitary surgery. Patient care in July is similar to care during other months, demonstrating that hospitals are adequately supervising surgical residents during this transition.
HOTAIRM1 competed endogenously with miR‐148a to regulate DLGAP1 in head and neck tumor cells
Authors: Zheng Mei , Liu Xingguang , Zhou Qin , Liu Gangli 
Published: June 2018

AbstractThis study is aimed to explore the regulatory effect of lncRNA HOTAIR/miR‐148a/DLGAP1 axis on head and neck tumor (HNT) cell growth, cell mobility, and invasiveness. HOTAIRM1, miR‐148a, and DLGAP1 level in HNT tissues and adjacent normal tissues were measured by qRT‐PCR. Cell Counting Kit‐8 (CCK‐8) and Transwell (migration and invasion) assay were used to survey the influence of HOTAIRM1, miR‐148a, and DLGAP1 on Fadu cells. Nude mouse xenograft was utilized to validate the influence of HOTAIRM1 in vivo. Dual‐luciferase reporter assay confirms the relationship between HOTAIRM1 and miR‐148a, miR‐148a, and DLGAP1. The expression level of HOTAIRM1 was downregulated in human HNT tissues and cells. Overexpression of HOTAIRM1 significantly moderated Fadu cells proliferation, apoptosis, migration, and invasion in vitro and impaired the tumorigenesis in vivo. The expression level of miR‐148a was upregulated in human HNT tissue compared to the adjacent tissues. We identified that miR‐148a was a target of HOTAIRM1 and its expression levels were reduced by HOTAIRM1. Transfection of miR‐148a mimics increased proliferation, migration, and invasion of Fadu cells. DLGAP1 was identified as a novel target of miR‐148a and its expression level was promoted by either HOTAIRM1 overexpression or miR‐148a knockdown. Overexpression of DLGAP1 also facilitated the cell viability and metastasis of Fadu cells. HOTAIRM1 was confirmed as a tumor suppressor via sponging miR‐148a and promote the expression of DLGAP1, which could be regarded as an important target for the prevention and treatment of HNT.
Low expression of WW domain‐containing oxidoreductase associates with hepatocellular carcinoma aggressiveness and recurrence after curative resection
Authors: Zhou Chenhao , Chen Wanyong , Sun Jialei , Atyah Manar , Yin Yirui , Zhang Wentao , Guo Lei , Ye Qinghai , Dong Qiongzhu , Shi Yi , Ren Ning 
Published: June 2018

AbstractWW domain‐containing oxidoreductase (WWOX), which has a protein‐interaction domain and is regarded to be a tumor suppressor, has been known to play an important role in anti‐angiogenesis and cancer progression. This study aimed to investigate prognostic values of WWOX expression in hepatocellular carcinoma (HCC) patients after hepatectomy. Additionally, we intended to formulate a valuable prognostic nomogram for HCCs. 182 HCC patients who underwent hepatectomy from January 2009 to January 2010 were enrolled in our study. qRT‐PCR, Western blot, and immunohistochemistry on tissue microarrays were then used to determine the expression levels of WWOX. An evaluation of the role of WWOX expression levels in the prognosis and outcome of patients was established. A decrease in the expression of WWOX was found when compared to adjacent tumor‐free tissues, which led to worse overall survival (OS) and recurrence‐free survival (RFS) and, therefore, was considered as an independent negative factor in the prognosis of HCC. Two nomograms, comprising WWOX, alpha‐fetoprotein (AFP), tumor size, and γ‐glutamyltransferase (γ‐GT), were constructed to obtain superior discriminatory abilities than conventional staging systems in terms of C‐index and clinical net benefit on decision curve analysis (DCA) for OS and RFS. Our data suggest that WWOX expression is strongly related to HCC post‐resection aggressiveness and recurrence. Additional advanced and accurate predictive model through the incorporation of WWOX into nomogram could help predict OS or RFS for HCC patients.
Chronic myelogenous leukemia on target
Authors: Némethová Veronika , Rázga Filip 
Published: June 2018

AbstractChronic myelogenous leukemia (CML) is commonly treated with tyrosine kinase inhibitors (TKIs) that inhibit the pro‐leukemic activity of the BCR‐ABL1 oncoprotein. Despite the therapeutic progress mediated by TKI use, off‐target effects, treatment‐induced drug resistance, and the limited effect of these drugs on CML stem cells (SCs) are major drawbacks frequently resulting in insufficient or unsustainable treatment. Therefore, intense research efforts have focused on development of improved TKIs and alternative treatment strategies to eradicate CML SCs. Alongside efforts to design superior protein inhibitors, the need to overcome the poor therapeutic effect of TKIs on CML SCs has led to a renaissance of antisense strategies, as they are reported as effective in more primitive cell types. Despite the greater drug design flexibility offered by antisense sequence variability and remarkable chemical improvements, antisense drugs exhibit unacceptable levels of off‐target effects, precluding them from large‐scale clinical testing. Recent advances in antisense drug design have led to a pioneering mRNA recognition concept that may offer a helping hand in eliminating off‐target effects, and has potential to bridge the gap between research and clinical practice.
Pharmacokinetics, Safety, and Tolerability of Rolapitant Administered Intravenously Following Single Ascending and Multiple Ascending Doses in Healthy Subjects
Authors: Wang Xiaodong , Zhang Zhi‐Yi , Wang Jing , Powers Dan , Arora Sujata , Lu Sharon , Kansra Vikram 
Published: June 2018

AbstractRolapitant is a selective and long‐acting neurokinin‐1 receptor antagonist approved in an oral formulation in combination with dexamethasone and a 5‐hydroxytryptamine type 3 receptor antagonist for the prevention of delayed chemotherapy‐induced nausea and vomiting in adults. The pharmacokinetic and safety profiles of intravenous (IV) rolapitant were evaluated in two open‐label, phase 1 trials in healthy subjects. Single ascending dose (SAD) and multiple ascending dose studies were conducted in one trial (PR‐11‐5012‐C), and a supratherapeutic SAD study was conducted in a separate trial (PR‐11‐5022‐C). In the SAD and supratherapeutic studies, rolapitant maximum plasma concentration, area under the plasma drug concentration‐time curve (AUC) from time zero to time of last measured concentration, and AUC from time zero to infinity increased dose‐proportionally following single IV infusions of 18 to 270 mg. In the multiple ascending dose study, following 10 daily IV infusions of rolapitant 18, 36, or 54 mg, the mean day 10:day 1 maximum concentration ratio was 1.97, 1.52, and 2.07, respectively, and the mean day 10:day 1 ratio of AUC from 0 to 24 hours was 4.30, 4.59, and 5.38, respectively, indicating drug accumulation over time. Across all studies, rolapitant was gradually eliminated from plasma, with a half‐life of 135‐231 hours. Rolapitant was safe and well tolerated across all studies, with no serious or severe rolapitant‐related treatment‐emergent adverse events. The most common rolapitant‐related treatment‐emergent adverse events were headache, dry mouth, and dizziness, which were predominantly mild in severity. Overall, the pharmacokinetic and safety profiles of IV rolapitant were consistent with those of the oral formulation.
Are seeds able to germinate before fruit color ripening? Evidence from six Neotropical bird‐dispersed plant species
Authors: Cruz‐Tejada Diana María , Acosta‐Rojas Diana Carolina , Stevenson Pablo R. 
Published: June 2018

AbstractMany plants attract seed dispersers and indicate the presence of ripe, fleshy fruits with coloration changes. If seed maturation is simultaneous with visual signs for frugivorous, a portion of seeds can be removed before being ready for dispersal. In this study, we tested the delay visual signal hypothesis (DVSH), which implies high reproductive success when seed maturation precedes the visual signal of the fruit ripening, limiting the dispersal of unviable seeds. We evaluated this hypothesis with six tropical species that have fruits with discrete coloration for the immature, intermediate, and mature stages, testing the prediction that the development of mature and intermediate seeds is similar. First, we verified that the coloration of three categories was differentiable with color analysis. Next, we carried out germination and viability tests (i.e., electrical conductivity [EC] and tetrazolium) as an approach to evaluate the germination potential along development. We found that the EC of three species decreased constantly during fruit ripening, suggesting that the seed maturation is a gradual process, with a substantial germination of intermediate seeds. In the other species, the conductivity of seeds of fruits with intermediate coloration was lower than that of mature fruit, because mature seeds are more affected by predators and pathogens. The tetrazolium tests indicated that the viability of seeds of three species increased with maturity and smaller differences between intermediate and mature stages were observed, supporting the DVSH. Only two species achieved high percentages of germination, and for Myrcia splendens, the pattern was very consistent with the hypothesis. We concluded that the germination and viability rates of the seeds of each plant species depend on many factors (e.g., dormancy and time of exposure to predators); however, for all the species studied, there is some evidence that seeds can germinate before they reach maturity by color.
Neurexin Superfamily Cell Membrane Receptor Contactin-Associated Protein Like-4 (Cntnap4) Is Involved in Neural EGFL-Like 1 (Nell-1)-Responsive Osteogenesis
Authors: Li Chenshuang , Zheng Zhong , Ha Pin , Chen Xiaoyan , Jiang Wenlu , Sun Shan , Chen Feng , Asatrian Greg , Berthiaume Emily A , Kim Jong Kil , Chen Eric C , Pang Shen , Zhang Xinli , Ting Kang , Soo Chia 
Published: June 2018

ABSTRACT

Contactin-associated protein-like 4 (Cntnap4) is a member of the neurexin superfamily of transmembrane molecules that have critical functions in neuronal cell communication. Cntnap4 knockout mice display decreased presynaptic gamma-aminobutyric acid (GABA) and increased dopamine release that is associated with severe, highly penetrant, repetitive, and perseverative movements commonly found in human autism spectrum disorder patients. However, no known function of Cntnap4 has been revealed besides the nervous system. Meanwhile, secretory protein neural EGFL-like 1 (Nell-1) is known to exert potent osteogenic effects in multiple small and large animal models without the off-target effects commonly found with bone morphogenetic protein 2. In this study, while searching for a Nell-1-specific cell surface receptor during osteogenesis, we identified and validated a ligand/receptor-like interaction between Nell-1 and Cntnap4 by demonstrating: 1) Nell-1 and Cntnap4 colocalization on the surface of osteogenic-committed cells; 2) high-affinity interaction between Nell-1 and Cntnap4; 3) abrogation of Nell-1-responsive Wnt and MAPK signaling transduction, as well as osteogenic effects, via Cntnap4 knockdown; and 4) replication of calvarial cleidocranial dysplasias-like defects observed in Nell-1-deficient mice in Wnt1-Cre-mediated Cntnap4-knockout transgenic mice. In aggregate, these findings indicate that Cntnap4 plays a critical role in Nell-1-responsive osteogenesis. Further, this is the first functional annotation for Cntnap4 in the musculoskeletal system. Intriguingly, Nell-1 and Cntnap4 also colocalize on the surface of human hippocampal interneurons, implicating Nell-1 as a potential novel ligand for Cntnap4 in the nervous system. This unexpected characterization of the ligand/receptor-like interaction between Nell-1 and Cntnap4 indicates a novel biological functional axis for Nell-1 and Cntnap4 in osteogenesis and, potentially, in neural development and function. © 2018 American Society for Bone and Mineral Research.
Adipocytes induce distinct gene expression profiles in mammary tumor cells and enhance inflammatory signaling in invasive breast cancer cells
Authors: Nickel Annina , Blücher Christina , Kadri Omaeir Al , Schwagarus Nancy , Müller Silvana , Schaab Michael , Thiery Joachim , Burkhardt Ralph , Stadler Sonja C. 
Published: June 2018

AbstractObesity is a known risk factor for breast cancer. Since obesity rates are constantly rising worldwide, understanding the molecular details of the interaction between adipose tissue and breast tumors becomes an urgent task. To investigate potential molecular changes in breast cancer cells induced by co-existing adipocytes, we used a co-culture system of different breast cancer cell lines (MCF-7 and T47D: ER+/PR+/HER2− and MDA-MB-231: ER−/PR−/HER2−) and murine 3T3-L1 adipocytes. Here, we report that co-culture with adipocytes revealed distinct changes in global gene expression pattern in the different breast cancer cell lines. Our microarray data revealed that in both ER+ cell lines, top upregulated genes showed significant enrichment for hormone receptor target genes. In triple-negative MDA-MB-231 cells, co-culture with adipocytes led to the induction of pro-inflammatory genes, mainly involving genes of the Nf-κB signaling pathway. Moreover, co-cultured MDA-MB-231 cells showed increased secretion of the pro-inflammatory interleukins IL-6 and IL-8. Using a specific NF-κB inhibitor, these effects were significantly decreased. Finally, migratory capacities were significantly increased in triple-negative breast cancer cells upon co-culture with adipocytes, indicating an enhanced aggressive cell phenotype. Together, our studies illustrate that factors secreted by adipocytes have a significant impact on the molecular biology of breast cancer cells.
Acetylcholine-modulated plasticity in reward-driven navigation: a computational study
Authors: Zannone Sara , Brzosko Zuzanna , Paulsen Ole , Clopath Claudia 
Published: June 2018

AbstractNeuromodulation plays a fundamental role in the acquisition of new behaviours. In previous experimental work, we showed that acetylcholine biases hippocampal synaptic plasticity towards depression, and the subsequent application of dopamine can retroactively convert depression into potentiation. We also demonstrated that incorporating this sequentially neuromodulated Spike-Timing-Dependent Plasticity (STDP) rule in a network model of navigation yields effective learning of changing reward locations. Here, we employ computational modelling to further characterize the effects of cholinergic depression on behaviour. We find that acetylcholine, by allowing learning from negative outcomes, enhances exploration over the action space. We show that this results in a variety of effects, depending on the structure of the model, the environment and the task. Interestingly, sequentially neuromodulated STDP also yields flexible learning, surpassing the performance of other reward-modulated plasticity rules.
Symmetry broken spin reorientation transition in epitaxial MgO/Fe/MgO layers with competing anisotropies
Authors: Martínez Isidoro , Tiusan Coriolan , Hehn Michel , Chshiev Mairbek , Aliev Farkhad G. 
Published: June 2018

AbstractThe observation of perpendicular magnetic anisotropy (PMA) at MgO/Fe interfaces boosted the development of spintronic devices based on ultrathin ferromagnetic layers. Yet, magnetization reversal in the standard magnetic tunnel junctions (MTJs) with competing PMA and in-plane anisotropies remains unclear. Here we report on the field induced nonvolatile broken symmetry magnetization reorientation transition from the in-plane to the perpendicular (out of plane) state at temperatures below 50 K. The samples were 10 nm thick Fe in MgO/Fe(100)/MgO as stacking components of V/MgO/Fe/MgO/Fe/Co double barrier MTJs with an area of 20 × 20 μm2. Micromagnetic simulations with PMA and different second order anisotropies at the opposite Fe/MgO interfaces qualitatively reproduce the observed broken symmetry spin reorientation transition. Our findings open the possibilities to develop multistate epitaxial spintronics based on competing magnetic anisotropies.
Assessing agreement among alternative climate change projections to inform conservation recommendations in the contiguous United States
Authors: Belote R. Travis , Carroll Carlos , Martinuzzi Sebastián , Michalak Julia , Williams John W. , Williamson Matthew A. , Aplet Gregory H. 
Published: June 2018

AbstractAddressing uncertainties in climate vulnerability remains a challenge for conservation planning. We evaluate how confidence in conservation recommendations may change with agreement among alternative climate projections and metrics of climate exposure. We assessed agreement among three multivariate estimates of climate exposure (forward velocity, backward velocity, and climate dissimilarity) using 18 alternative climate projections for the contiguous United States. For each metric, we classified maps into quartiles for each alternative climate projections, and calculated the frequency of quartiles assigned for each gridded location (high quartile frequency = more agreement among climate projections). We evaluated recommendations using a recent climate adaptation heuristic framework that recommends emphasizing various conservation strategies to land based on current conservation value and expected climate exposure. We found that areas where conservation strategies would be confidently assigned based on high agreement among climate projections varied substantially across regions. In general, there was more agreement in forward and backward velocity estimates among alternative projections than agreement in estimates of local dissimilarity. Consensus of climate predictions resulted in the same conservation recommendation assignments in a few areas, but patterns varied by climate exposure metric. This work demonstrates an approach for explicitly evaluating alternative predictions in geographic patterns of climate change.