bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical Determinants and Reduced Models of the Rapid Cooling of Urban Surfaces During Rainfall
Authors: Omidvar Hamidreza , Bou‐Zeid Elie , Chiaramonte Maurizio 
Published: March 2019

AbstractUsing a detailed model, sensitivity analyses are conducted to identify the leading physical determinants and heat fluxes that control energy exchange between surface runoff and urban pavements during rainfall. These analyses confirm that pavement characteristics, such as albedo and thermal effusivity, strongly influence the initial temperature of the pavement before rain starts. Moreover, this sensitivity propagates to the runoff and pavement temperatures as well as to sensible heat and evaporation fluxes during and after rainfall. Heat transfer inside the runoff and pavement during rainfall is also very sensitive to the rain temperature and is the leading process in surface cooling (the classically important sensible and latent heat fluxes to the atmosphere are minor contributors). Finally, based on the findings from the sensitivity analyses, using a bulk energy approach, a reduced version of the full model is proposed. This simple model uses the spatially averaged temperatures of the runoff and pavement and can predict their temperatures and the associated energy fluxes almost as accurately as the full model. The reduced model has the added advantages of computational efficiency and simplicity of implementation in coarse earth system models.
micro-RNAs dependent regulation of DNMT and HIF1α gene expression in thrombotic disorders
Authors: Vijay Aatira , Jha Prabhash Kumar , Garg Iti , Sharma Manish , Ashraf Mohammad Zahid , Kumar Bhuvnesh 
Published: March 2019

AbstractMicroRNAs (miRNAs) are involved in a wide variety of cellular processes and post-transcriptionally regulate several mechanism and diseases. However, contribution of miRNAs functioning during hypoxia and DNA methylation together is less understood. The current study was aimed to find a shared miRNAs signature upstream to hypoxia (via HIF gene family members) and methylation (via DNMT gene family members). This was followed by the global validation of the hypoxia related miRNA signature using miRNA microarray meta-analysis of the hypoxia induced human samples. We further concluded the study by looking into thrombosis related terms and pathways enriched during protein-protein interaction (PPI) network analysis of these two sets of gene family. Network prioritization of these shared miRNAs reveals miR-129, miR-19band miR-23b as top regulatory miRNAs. A comprehensive meta-analysis of microarray datasets of hypoxia samples revealed 29 differentially expressed miRNAs. GSEA of the interacting genes in the DNMT-HIF PPI network indicated thrombosis associated pathways including “Hemostasis”, “TPO signaling pathway” and “angiogenesis”. Interestingly, the study has generated a novel database of candidate miRNA signatures shared between hypoxia and methylation, and their relation to thrombotic pathways, which might aid in the development of potential therapeutic biomarkers.
Hemodynamic responses to emotional speech in two-month-old infants imaged using diffuse optical tomography
Authors: Shekhar Shashank , Maria Ambika , Kotilahti Kalle , Huotilainen Minna , Heiskala Juha , Tuulari Jetro J. , Hirvi Pauliina , Karlsson Linnea , Karlsson Hasse , Nissilä Ilkka 
Published: March 2019

AbstractEmotional speech is one of the principal forms of social communication in humans. In this study, we investigated neural processing of emotional speech (happy, angry, sad and neutral) in the left hemisphere of 21 two-month-old infants using diffuse optical tomography. Reconstructed total hemoglobin (HbT) images were analysed using adaptive voxel-based clustering and region-of-interest (ROI) analysis. We found a distributed happy > neutral response within the temporo-parietal cortex, peaking in the anterior temporal cortex; a negative HbT response to emotional speech (the average of the emotional speech conditions < baseline) in the temporo-parietal cortex, neutral > angry in the anterior superior temporal sulcus (STS), happy > angry in the superior temporal gyrus and posterior superior temporal sulcus, angry < baseline in the insula, superior temporal sulcus and superior temporal gyrus and happy < baseline in the anterior insula. These results suggest that left STS is more sensitive to happy speech as compared to angry speech, indicating that it might play an important role in processing positive emotions in two-month-old infants. Furthermore, happy speech (relative to neutral) seems to elicit more activation in the temporo-parietal cortex, thereby suggesting enhanced sensitivity of temporo-parietal cortex to positive emotional stimuli at this stage of infant development.
Carbohydrate Metabolic Compensation Coupled to High Tolerance to Oxidative Stress in Ticks
Authors: Della Noce Bárbara , Carvalho Uhl Marcelle Vianna de , Machado Josias , Waltero Camila Fernanda , de Abreu Leonardo Araujo , da Silva Renato Martins , da Fonseca Rodrigo Nunes , de Barros Cintia Monteiro , Sabadin Gabriela , Konnai Satoru , da Silva Vaz Itabajara , Ohashi Kazuhiko , Logullo Carlos 
Published: March 2019

AbstractReactive oxygen species (ROS) are natural byproducts of metabolism that have toxic effects well documented in mammals. In hematophagous arthropods, however, these processes are not largely understood. Here, we describe that Rhipicephalus microplus ticks and embryonic cell line (BME26) employ an adaptive metabolic compensation mechanism that confers tolerance to hydrogen peroxide (H2O2) at concentrations too high for others organisms. Tick survival and reproduction are not affected by H2O2 exposure, while BME26 cells morphology was only mildly altered by the treatment. Furthermore, H2O2-tolerant BME26 cells maintained their proliferative capacity unchanged. We evaluated several genes involved in gluconeogenesis, glycolysis, and pentose phosphate pathway, major pathways for carbohydrate catabolism and anabolism, describing a metabolic mechanism that explains such tolerance. Genetic and catalytic control of the genes and enzymes associated with these pathways are modulated by glucose uptake and energy resource availability. Transient increase in ROS levels, oxygen consumption, and ROS-scavenger enzymes, as well as decreased mitochondrial superoxide levels, were indicative of cell adaptation to high H2O2 exposure, and suggested a tolerance strategy developed by BME26 cells to cope with oxidative stress. Moreover, NADPH levels increased upon H2O2 challenge, and this phenomenon was sustained mainly by G6PDH activity. Interestingly, G6PDH knockdown in BME26 cells did not impair H2O2 tolerance, but generated an increase in NADP-ICDH transcription. In agreement with the hypothesis of a compensatory NADPH production in these cells, NADP-ICDH knockdown increased G6PDH relative transcript level. The present study unveils the first metabolic evidence of an adaptive mechanism to cope with high H2O2 exposure and maintain redox balance in ticks.
Endophytic Bacterial Communities Associated with Roots and Leaves of Plants Growing in Chilean Extreme Environments
Authors: Zhang Qian , Acuña Jacquelinne J. , Inostroza Nitza G. , Mora María Luz , Radic Sergio , Sadowsky Michael J. , Jorquera Milko A. 
Published: March 2019

AbstractSeveral studies have demonstrated the relevance of endophytic bacteria on the growth and fitness of agriculturally-relevant plants. To our knowledge, however, little information is available on the composition, diversity, and interaction of endophytic bacterial communities in plants struggling for existence in the extreme environments of Chile, such as the Atacama Desert (AD) and Patagonia (PAT). The main objective of the present study was to analyze and compare the composition of endophytic bacterial communities associated with roots and leaves of representative plants growing in Chilean extreme environments. The plants sampled were: Distichlis spicate and Pluchea absinthioides from the AD, and Gaultheria mucronata and Hieracium pilosella from PAT. The abundance and composition of their endophytic bacterial communities was determined by quantitative PCR and high–throughput sequencing of 16S rRNA, respectively. Results indicated that there was a greater abundance of 16S rRNA genes in plants from PAT (1013 to 1014 copies g−1 DNA), compared with those from AD (1010 to 1012 copies g−1 DNA). In the AD, a greater bacterial diversity, as estimated by Shannon index, was found in P. absinthioides, compared with D. spicata. In both ecosystems, the greater relative abundances of endophytes were mainly attributed to members of the phyla Proteobacteria (14% to 68%), Firmicutes (26% to 41%), Actinobacteria (6 to 23%) and Bacteroidetes (1% to 21%). Our observations revealed that most of operational taxonomic units (OTUs) were not shared between tissue samples of different plant species in both locations, suggesting the effect of the plant genotype (species) on the bacterial endophyte communities in Chilean extreme environments, where Bacillaceae and Enterobacteriacea could serve as keystone taxa as revealed our linear discriminant analysis.
Anti-alcohol abuse drug disulfiram inhibits human PHGDH via disruption of its active tetrameric form through a specific cysteine oxidation
Authors: Spillier Quentin , Vertommen Didier , Ravez Séverine , Marteau Romain , Thémans Quentin , Corbet Cyril , Feron Olivier , Wouters Johan , Frédérick Raphaël 
Published: March 2019

AbstractDue to rising costs and the difficulty to identify new targets, drug repurposing appears as a viable strategy for the development of new anti-cancer treatments. Although the interest of disulfiram (DSF), an anti-alcohol drug, to treat cancer was reported for many years, it is only very recently that one anticancer mechanism-of-action was highlighted. This would involve the inhibition of the p97 segregase adaptor NPL4, which is essential for the turnover of proteins involved in multiple regulatory and stress-response intracellular pathways. However, recently DSF was also reported as one of the first phosphoglycerate dehydrogenase (PHGDH) inhibitors, a tetrameric enzyme catalyzing the initial step of the serine synthetic pathway that is highly expressed in numerous cancer types. Here, we investigated the structure-activity relationships (SAR) of PHGDH inhibition by disulfiram analogues as well as the mechanism of action of DSF on PHGDH via enzymatic and cell-based evaluation, mass spectrometric and mutagenesis experiments.
The VQ motif-containing proteins in the diploid and octoploid strawberry
Authors: Garrido-Gala José , Higuera José Javier , Muñoz-Blanco Juan , Amil-Ruiz Francisco , Caballero José L. 
Published: March 2019

AbstractThe plant VQ motif-containing proteins are a recently discovered class of plant regulatory proteins interacting with WRKY transcription factors capable of modulate their activity as transcriptional regulators. The short VQ motif (FxxhVQxhTG) is the main element in the WRKY-VQ interaction, whereas a newly identified variable upstream amino acid motif appears to be determinant for the WRKY specificity. The VQ family has been studied in several species and seems to play important roles in a variety of biological processes, including response to biotic and abiotic stresses. Here, we present a systematic study of the VQ family in both diploid (Fragaria vesca) and octoploid (Fragaria x ananassa) strawberry species. Thus, twenty-five VQ-encoding genes were identified and twenty-three were further confirmed by gene expression analysis in different tissues and fruit ripening stages. Their expression profiles were also studied in F. ananassa fruits affected by anthracnose, caused by the ascomycete fungus Colletotrichum, a major pathogen of strawberry, and in response to the phytohormones salicylic acid and methyl-jasmonate, which are well established as central stress signals to regulate defence responses to pathogens. This comprehensive analysis sheds light for a better understanding of putative implications of members of the VQ family in the defence mechanisms against this major pathogen in strawberry.
Inhibition of NLRP3 inflammasome activation by cell-permeable stapled peptides
Authors: Pal Arumay , Neo Kurt , Rajamani Lakshminarayanan , Ferrer Fernando Jose , Lane David P. , Verma Chandra S. , Mortellaro Alessandra 
Published: March 2019

AbstractInterleukin-1β (IL-1β) is a major cytokine that initiates and enhances inflammatory responses. Excessive IL-1β production is a characteristic of most chronic inflammatory diseases, including atherosclerosis, type 2 diabetes, and obesity, which affect a large proportion of the global population. The production of bioactive IL-1β is mediated by a caspase-1-activating complex known as an ‘inflammasome’. The NLRP3 inflammasome has been associated with several human inflammatory and autoimmune diseases and represents a potential therapeutic target for disrupting IL-1β production. We used molecular modeling guided by molecular dynamics simulations to design α-helical stapled peptides targeting the pyrin domain of the adaptor protein ASC to interrupt the development of its filament, which is crucial for NLRP3 inflammasome formation. The peptides were effectively internalized by human monocytic cells and efficiently suppressed the release of the inflammasome-regulated cytokines IL-1β and IL-18, following exogenous activation of the NLRP3 inflammasome. The peptides reduced ASC speck formation and caspase-1 processing thereby suppressing pro-IL-1β processing and release of active IL-1β. This is the first demonstration of the successful use of stapled peptides designed to target the adaptor protein ASC, and can be extended to other inflammatory pathways to disrupt excessive IL-1β production.
Human herpesvirus infections and dementia or mild cognitive impairment: a systematic review and meta-analysis
Authors: Warren-Gash Charlotte , Forbes Harriet J. , Williamson Elizabeth , Breuer Judith , Hayward Andrew C. , Mavrodaris Angelique , Ridha Basil H. , Rossor Martin N. , Thomas Sara L. , Smeeth Liam 
Published: March 2019

AbstractInterest is growing in the role of infectious agents in the pathogenesis of dementia, but current evidence is limited. We conducted a systematic review and meta-analysis to investigate the effect of any of eight human herpesviruses on development of dementia or mild cognitive impairment (MCI). We searched the Cochrane Library, Embase, Global Health, Medline, PsycINFO, Scopus, Web of Science, clinical trials registers and grey literature sources from inception to December 2017 for observational studies with cohort, case control or self-controlled designs, or randomised controlled trials of interventions against herpesviruses. Pooled effect estimates and 95% confidence intervals (CIs) were generated through random effects meta-analyses across studies with the same design, outcome, and virus type, method and site of measurement. We included 57 studies across various geographic settings. Past infection with herpesviruses, measured by IgG seropositivity, was generally not associated with dementia risk. A single cohort study rated moderate quality showed an association between varicella zoster virus reactivation (ophthalmic zoster) and incident dementia (HR 2.97; 95%CI, 1.89 to 4.66). Recent infection with, or reactivation of, herpes simplex virus type 1 or type 1/2 unspecified, cytomegalovirus and human herpes virus-6 measured by serum IgM, high titre IgG or clinical disease may be associated with dementia or MCI, though results were inconsistent across studies and overall evidence rated very low quality. Longitudinal population studies with robust repeated virus measurements taken sufficiently proximal to dementia onset are needed to establish whether, when and among whom herpesviruses affect dementia risk.
Development and Validation of Nomograms for Malignancy Prediction in Soft Tissue Tumors Using Magnetic Resonance Imaging Measurements
Authors: Lee Ji Hyun , Yoon Young Cheol , Jin Wook , Cha Jang Gyu , Kim Seonwoo 
Published: March 2019

AbstractThe objective of this study was to develop, validate, and compare nomograms for malignancy prediction in soft tissue tumors (STTs) using conventional and diffusion-weighted magnetic resonance imaging (MRI) measurements. Between May 2011 and December 2016, 239 MRI examinations from 236 patients with pathologically proven STTs were included retrospectively and assigned randomly to training (n = 100) and validation (n = 139) cohorts. MRI of each lesion was reviewed to assess conventional and diffusion-weighted imaging (DWI) measurements. Multivariate nomograms based on logistic regression analyses were built using conventional measurements with and without DWI measurements. Predictive accuracy was measured using the concordance index (C-index) and calibration plots. Statistical differences between the C-indexes of the two models were analyzed. Models were validated by leave-one-out cross-validation and by using a validation cohort. The mean lesion size, presence of infiltration, edema, and the absence of the split fat sign were significant and independent predictors of malignancy and included in the conventional model. In addition to these measurements, the mean and minimum apparent diffusion coefficient values were included in the DWI model. The DWI model exhibited significantly higher diagnostic performance only in the validation cohort (training cohort, 0.899 vs. 0.886, P = 0.284; validation cohort, 0.791 vs. 0.757, P = 0.020). Calibration plots showed fair agreements between the nomogram predictions and actual observations in both cohorts. In conclusion, nomograms using MRI features as variables can be utilized to predict the malignancy probability in patients with STTs. There was no definite gain in diagnostic accuracy when additional DWI features were used.
Autaptic cultures of human induced neurons as a versatile platform for studying synaptic function and neuronal morphology
Authors: Fenske Pascal , Grauel M. Katharina , Brockmann Marisa M. , Dorrn Anja L. , Trimbuch Thorsten , Rosenmund Christian 
Published: March 2019

AbstractRecently developed technology to differentiate induced pluripotent stem cells (iPSCs) into human induced neurons (iNs) provides an exciting opportunity to study the function of human neurons. However, functional characterisations of iNs have been hampered by the reliance on mass culturing protocols which do not allow assessment of synaptic release characteristics and neuronal morphology at the individual cell level with quantitative precision. Here, we have developed for the first time a protocol to generate autaptic cultures of iPSC-derived iNs. We show that our method efficiently generates mature, autaptic iNs with robust spontaneous and action potential-driven synaptic transmission. The synaptic responses are sensitive to modulation by metabotropic receptor agonists as well as potentiation by acute phorbol ester application. Finally, we demonstrate loss of evoked and spontaneous release by Unc13A knockdown. This culture system provides a versatile platform allowing for quantitative and integrative assessment of morphophysiological and molecular parameters underlying human synaptic transmission.
pH effects on plant calcium fluxes: lessons from acidification-mediated calcium elevation induced by the γ-glutamyl-leucine dipeptide identified from Phytophthora infestans
Authors: Westphal Lore , Strehmel Nadine , Eschen-Lippold Lennart , Bauer Nicole , Westermann Bernhard , Rosahl Sabine , Scheel Dierk , Lee Justin 
Published: March 2019

AbstractCytosolic Ca2+ ([Ca2+]cyt) elevation is an early signaling response upon exposure to pathogen-derived molecules (so-called microbe-associated molecular patterns, MAMPs) and has been successfully used as a quantitative read-out in genetic screens to identify MAMP receptors or their associated components. Here, we isolated and identified by mass spectrometry the dipeptide γ-Glu-Leu as a component of a Phytophthora infestans mycelium extract that induces [Ca2+]cyt elevation. Treatment of Arabidopsis seedlings with synthetic γ-Glu-Leu revealed stimulatory effects on defense signaling, including a weak enhancement of the expression of some MAMP-inducible genes or affecting the refractory period to a second MAMP elicitation. However, γ-Glu-Leu is not a classical MAMP since pH adjustment abolished these activities and importantly, the observed effects of γ-Glu-Leu could be recapitulated by mimicking extracellular acidification. Thus, although γ-Glu-Leu can act as a direct agonist of calcium sensing receptors in animal systems, the Ca2+-mobilizing activity in plants reported here is due to acidification. Low pH also shapes the Ca2+ signature of well-studied MAMPs (e.g. flg22) or excitatory amino acids such as glutamate. Overall, this work serves as a cautionary reminder that in defense signaling studies where Ca2+ flux measurements are concerned, it is important to monitor and consider the effects of pH.
Maritime Hunter-Gatherers Adopt Cultivation at the Farming Extreme of Northern Europe 5000 Years Ago
Authors: Vanhanen Santeri , Gustafsson Stefan , Ranheden Håkan , Björck Niclas , Kemell Marianna , Heyd Volker 
Published: March 2019

AbstractThe dynamics of the origins and spread of farming are globally debated in anthropology and archaeology. Lately, numerous aDNA studies have turned the tide in favour of migrations, leaving only a few cases in Neolithic Europe where hunter-gatherers might have adopted agriculture. It is thus widely accepted that agriculture was expanding to its northern extreme in Sweden c. 4000 BC by migrating Funnel Beaker Culture (FBC) farmers. This was followed by intense contacts with local hunter-gatherers, leading to the development of the Pitted Ware Culture (PWC), who nonetheless relied on maritime prey. Here, we present archaeobotanical remains from Sweden and the Åland archipelago (Finland) showing that PWC used free-threshing barley and hulled and free-threshing wheat from c. 3300 BC. We suggest that these hunter-gatherers adopted cultivation from FBC farmers and brought it to islands beyond the 60th parallel north. Based on directly dated grains, land areas suitable for cultivation, and absence of signs of exchange with FBC in Sweden, we argue that PWC cultivated crops in Åland. While we have isotopic and lipid-biomarker proof that their main subsistence was still hunting/fishing/gathering, we argue small-scale cereal use was intended for ritual feasts, when cereal products could have been consumed with pork.
A novel ex vivo tumor system identifies Src-mediated invasion and metastasis in mesenchymal tumor cells in non-small cell lung cancer
Authors: Padhye Aparna , Ungewiss Christin , Fradette Jared J. , Rodriguez B. Leticia , Albritton Jacob L. , Miller Jordan S. , Gibbons Don L. 
Published: March 2019

AbstractLung cancer is the foremost cause of cancer related deaths in the U.S. It is a heterogeneous disease composed of genetically and phenotypically distinct tumor cells surrounded by heterotypic cells and extracellular matrix dynamically interacting with the tumor cells. Research in lung cancer is often restricted to patient-derived tumor specimens, in vitro cell cultures and limited animal models, which fail to capture the cellular or microenvironment heterogeneity of the tumor. Therefore, our knowledge is primarily focused on cancer-cell autonomous aberrations. For a fundamental understanding of lung cancer progression and an exploration of therapeutic options, we focused our efforts to develop an Ex Vivo Tumor platform to culture tumors in 3D matrices, which retains tumor cell heterogeneity arising due to in vivo selection pressure and environmental influences and recapitulate responses of tumor cells to external manipulations. To establish this model, implanted syngeneic murine tumors from a mutant KRAS/p53 model were harvested to yield multicellular tumor aggregates followed by culture in 3D extracellular matrices. Using this system, we identified Src signaling as an important driver of invasion and metastasis in lung cancer and demonstrate that EVTs are a robust experimental tool bridging the gap between conventional in vitro and in vivo models.