bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ectopic expression of Snord115 in choroid plexus interferes with editing but not splicing of 5-Ht2c receptor pre-mRNA in mice
Authors: Raabe Carsten A. , Voss Reinhard , Kummerfeld Delf-Magnus , Brosius Juergen , Galiveti Chenna R. , Wolters Anna , Seggewiss Jochen , Huge Andreas , Skryabin Boris V. , Rozhdestvensky Timofey S. 
Published: March 2019

AbstractSerotonin 5-HT2C receptor is a G-protein coupled excitatory receptor that regulates several biochemical pathways and has been implicated in obesity, mental state, sleep cycles, autism, neuropsychiatric disorders and neurodegenerative diseases. The activity of 5-HT2CR is regulatedviaalternative splicing and A to I editing of exon Vb of its pre-mRNA. Snord115 is a small nucleolar RNA that is expressed in mouse neurons and displays an 18-nucleotide base complementary to exon Vb of 5-HT2CR pre-mRNA. For almost two decades this putative guide element of Snord115 has wandered like a ghost through the literature in attempts to elucidate the biological significance of this complementarity. In mice, Snord115 is expressed in neurons and absent in the choroid plexus where, in contrast, 5-Ht2cr mRNA is highly abundant. Here we report the analysis of 5-Ht2cr pre-mRNA posttranscriptional processingviaRNA deep sequencing in a mouse model that ectopically expresses Snord115 in the choroid plexus. In contrast to previous reports, our analysis demonstrated that Snord115 does not control alternative splicing of 5-Ht2cr pre-mRNAin vivo. We identified a modest, yet statistically significant reduction of 5-Ht2cr pre-mRNA A to I editing at the major A, B, C and D sites. We suggest that Snord115 and exon Vb of 5Ht2cr pre-mRNA form a double-stranded structure that is subject to ADAR-mediated A to I editing. To the best of our knowledge, this is the first comprehensive Snord115 gain-of-function analysis based onin vivomouse models.
Engulfment, persistence and fate of Bdellovibrio bacteriovorus predators inside human phagocytic cells informs their future therapeutic potential
Authors: Raghunathan Dhaarini , Radford Paul M. , Gell Christopher , Negus David , Moore Christopher , Till Rob , Tighe Patrick J. , Wheatley Sally P. , Martinez-Pomares Luisa , Sockett R. Elizabeth , Tyson Jess 
Published: March 2019

AbstractIn assessing the potential of predatory bacteria, such as Bdellovibrio bacteriovorus, to become live therapeutic agents against bacterial infections, it is crucial to understand and quantify Bdellovibrio host cell interactions at a molecular level. Here, we quantify the interactions of live B. bacteriovorus with human phagocytic cells, determining the uptake mechanisms, persistence, associated cytokine responses and intracellular trafficking of the non-growing B. bacteriovorus in PMA-differentiated U937 cells. B. bacteriovorus are engulfed by U937 cells and persist for 24 h without affecting host cell viability and can be observed microscopically and recovered and cultured post-uptake. The uptake of predators is passive and depends on the dynamics of the host cell cytoskeleton; the engulfed predators are eventually trafficked through the phagolysosomal pathway of degradation. We have also studied the prevalence of B. bacteriovorus specific antibodies in the general human population. Together, these results quantify a period of viable persistence and the ultimate fate of B. bacteriovorus inside phagocytic cells. They provide new knowledge on predator availability inside hosts, plus potential longevity and therefore potential efficacy as a treatment in humans and open up future fields of work testing if predators can prey on host-engulfed pathogenic bacteria.
Two-tailed RT-qPCR panel for quality control of circulating microRNA studies
Authors: Androvic Peter , Romanyuk Nataliya , Urdzikova-Machova Lucia , Rohlova Eva , Kubista Mikael , Valihrach Lukas 
Published: March 2019

AbstractCirculating cell-free microRNAs are promising candidates for minimally invasive clinical biomarkers for the diagnosis, prognosis and monitoring of many human diseases. Despite substantial efforts invested in the field, the research so far has failed to deliver expected results. One of the contributing factors is general lack of agreement between various studies, partly due to the considerable technical challenges accompanying the workflow. Pre-analytical variables including sample collection, RNA isolation, and quantification are sources of bias that may hamper biological interpretation of the results. Here, we present a Two-tailed RT-qPCR panel for quality control, monitoring of technical performance, and optimization of microRNA profiling experiments from biofluid samples. The Two-tailed QC (quality control) panel is based on two sets of synthetic spike-in molecules and three endogenous microRNAs that are quantified with the highly specific Two-tailed RT-qPCR technology. The QC panel is a cost-effective way to assess quality of isolated microRNA, degree of inhibition, and erythrocyte contamination to ensure technical soundness of the obtained results. We provide assay sequences, detailed experimental protocol and guide to data interpretation. The application of the QC panel is demonstrated on the optimization of RNA isolation from biofluids with the miRNeasy Serum/Plasma Advanced Kit (Qiagen).
Primary lung cancer samples cultured under microenvironment-mimetic conditions enrich for mesenchymal stem-like cells that promote metastasis
Authors: Saforo Douglas , Omer Linda , Smolenkov Andrei , Barve Aditya , Casson Lavona , Boyd Nolan , Clark Geoffrey , Siskind Leah , Beverly Levi 
Published: March 2019

AbstractThe tumor microenvironment (TME) is composed of a heterogeneous biological ecosystem of cellular and non-cellular elements including transformed tumor cells, endothelial cells, immune cells, activated fibroblasts or myofibroblasts, stem and progenitor cells, as well as the cytokines and matrix that they produce. The constituents of the TME stroma are multiple and varied, however cancer associated fibroblasts (CAF) and their contribution to the TME are important in tumor progression. CAF are hypothesized to arise from multiple progenitor cell types, including mesenchymal stem cells. Currently, isolation of TME stroma from patients is complicated by issues such as limited availability of biopsy material and cell stress incurred during lengthy adaptation to atmospheric oxygen (20% O2) in cell culture, limiting pre-clinical studies of patient tumor stromal interactions. Here we describe a microenvironment mimetic in vitro cell culturing system that incorporates elements of the in vivo lung environment, including lung fibroblast derived extracellular matrix and physiological hypoxia (5% O2). Using this system, we easily isolated and rapidly expanded stromal progenitors from patient lung tumor resections without complex sorting methods or growth supplements. These progenitor populations retained expression of pluripotency markers, secreted factors associated with cancer progression, and enhanced tumor cell growth and metastasis. An understanding of the biology of these progenitor cell populations in a TME-like environment may advance our ability to target these cells and limit their effects on promoting cancer metastasis.
Intestine specific regulation of pig cytidine-5′-monophospho-N-acetylneuraminic acid hydroxylase gene for N-glycolylneuraminic acid biosynthesis
Authors: Song Kwon-Ho , Kwak Choong-Hwan , Chung Tae-Wook , Ha Sun-Hyung , Park Jun-Young , Ha Ki-Tae , Cho Seung-Hak , Lee Young-Choon , Kim Cheorl-Ho 
Published: March 2019

AbstractN-glycolylneuraminic acid (Neu5Gc), a generic form of sialic acid, is enzymatically synthesized by cytidine-5′-monophospho-N-acetylneuraminic acid hydroxylase (CMAH). Although expression of pig CMAH gene pcmah encoding CMAH has been reported to be regulated by pathogenic infection and developmental processes, little is known about the mechanisms underlying the regulation of pcmah gene expression. The objective of this study was to determine mechanism(s) involved in intestine specific regulation of pcmah gene by identifying several cis-acting elements and nuclear transcription factors that could directly interact with these cis-acting elements. We identified intestine specific promoter region (Pi) of pcmah gene located at upstream regions of the 5′flanking region of exon 1a and found that the promoter region is responsible for the transcriptional regulation of 5′pcmah-1. Based on reporter assays using serially constructed luciferase genes with each deleted promoter, we demonstrated that the Pi promoter activity was more active in intestinal IPI-2I cells than that in kidney PK15 cells, corresponding to both mRNA expression patterns in the two cell lines. In addition, we found that Sp1 transcription factor was necessary for basal activity of Pi promoter and that Ets-1 contributed to intestine-specific activity of Pi promoter. This study helps us understand transcriptional regulation of pcmah in the intestine of pig tissues. It also allows us to consider potential roles of Neu5Gc in interaction with environmental factors present in the intestinal tissue during pathogenic infection and developmental process.
Limited freshwater cap in the Eocene Arctic Ocean
Authors: Neville Lisa A. , Grasby Stephen E. , McNeil David H. 
Published: March 2019

AbstractRemains of the freshwater fern Azolla, found in Eocene (~50 Ma ago) sediments in the modern central Arctic Ocean, have been used to suggest that seasonal freshwater caps covered the entire Arctic Ocean during that time, with significant impact on global ocean circulation and climate. However, these records are located on the Lomonosov Ridge, which during the Eocene was a continental fragment barely rifted from Eurasia, separating the smaller Eurasian Basin from the much larger Amerasian Basin to the west. As such, the Lomonosov Ridge does not necessarily record environmental conditions of the broader Arctic Ocean. We tested the hypothesis of freshwater caps by examining sediment records from the western Amerasian Basin. Here we show that in the larger Amerasian Basin the Azolla event is associated with marine microfauna along with allochthonous (terrestrially sourced) organic matter. We propose that Azolla events are related to an increased hydrologic cycle washing terrestrially sourced Azolla, and other organics, into the Arctic Ocean. If freshwater caps did occur, then they were at best restricted to the small Eurasian Basin and would have had a limited impact on Eocene global climate, contrary to current models.
Three-dimensional geometry of human tibial anterior curvature in chronologically distinct population samples of Central Europeans (2900 BC – 21st century AD)
Authors: Brzobohatá Hana , Krajíček Václav , Velemínský Petr , Velemínská Jana 
Published: March 2019

AbstractSeveral lines of bioarchaeological research have confirmed the gradual decline in lower limb loading among past human populations, beginning with the transition to agriculture. The goal of this study was to assess whether human tibial curvature reflects this decline, with a special emphasis on the time-span during which the pace of technological change has been the most rapid. Our study is the first (1) to apply longitudinal curvature analysis in the antero-posterior (A–P) and medio-lateral (M–L) planes to the human tibia, and (2) that incorporates a broad temporal population sample including the periods of intensification of agriculture, urbanization and industrialization (from 2900 BC to the 21stcentury AD; N = 435) within Czech territories. Using three-dimensional geometric morphometrics, we investigated whether anterior tibial curvature mirrors assumed diminishing lower limb loading between prehistoric and industrialized societies and explored its shape in all three dimensions. Results showed the continuous trend of A–P straightening of the shaft. This straightening was associated with a relative sigmoidal curve accentuation in the M-L plane. Given the timescale involved and the known phenomenon of declining mobility, such adaptive changes in bone geometry can be interpreted in terms of the diminishing biomechanical demands on the tibia under different living conditions.
Focus Tracking System for Femtosecond Laser Machining using Low Coherence Interferometry
Authors: Raele Marcus Paulo , De Pretto Lucas Ramos , de Rossi Wagner , Vieira Nilson Dias , Samad Ricardo Elgul 
Published: March 2019

AbstractWe designed a real time, single-laser focus tracking system using low coherence properties of the machining femtosecond laser itself in order to monitor and correct the sample position relative to the focal plane. Using a Michelson Interferometer, the system collects data arising from part of the beam backscattered at the ablation spot. The data is analyzed by a custom software for position correction (employing an XYZ automated translation stage). With the focus tracking enabled we were able to etch channels with a stable cross-section profile on a bovine tooth with relief amplitude tens of times greater than the Rayleigh length of the system, keeping the sample inside the confocal parameter during most of the processing time. Moreover, the system is also capable of monitoring crater depth evolution during the ablation process, allowing for material removal assessment.
Effects of species traits and environmental predictors on performance and transferability of ecological niche models
Authors: Regos Adrián , Gagne Laura , Alcaraz-Segura Domingo , Honrado João P. , Domínguez Jesús 
Published: March 2019

AbstractThe ability of ecological niche models (ENMs) to produce robust predictions for different time frames (i.e. temporal transferability) may be hindered by a lack of ecologically relevant predictors. Model performance may also be affected by species traits, which may reflect different responses to processes controlling species distribution. In this study, we tested four primary hypotheses involving the role of species traits and environmental predictors in ENM performance and transferability. We compared the predictive accuracy of ENMs based upon (1) climate, (2) land-use/cover (LULC) and (3) ecosystem functional attributes (EFAs), and (4) the combination of these factors for 27 bird species within and beyond the time frame of model calibration. The combination of these factors significantly increased both model performance and transferability, highlighting the need to integrate climate, LULC and EFAs to improve biodiversity projections. However, the overall model transferability was low (being only acceptable for less than 25% of species), even under a hierarchical modelling approach, which calls for great caution in the use of ENMs to predict bird distributions under global change scenarios. Our findings also indicate that positive effects of species traits on predictive accuracy within model calibration are not necessarily translated into higher temporal transferability.
Facile synthesis of graphene-tin oxide nanocomposite derived from agricultural waste for enhanced antibacterial activity against Pseudomonas aeruginosa
Authors: Mohan Anu N. , B Manoj , Panicker Sandhya 
Published: March 2019

AbstractAntibacterial screening of graphene-tin oxide nanocomposites synthesized from carbonized wood and coconut shell is investigated against Pseudomonas aeruginosa for the first time. Efficient and facile one step hydrothermal process adopted in the present work for the synthesis of graphene-tin oxide nanoparticles provides an ideal method for the economic large-scale production of the same. Graphene-tin oxide nanocomposites derived from wood charcoal possess a spherical morphology whereas rod like structures are seen in the case of coconut shell derivatives. An excitation independent fluorescence response is observed in graphene-tin oxide nanohybrids while graphene oxide nanostructures exhibited an excitation dependent behavior. These hydrophilic nanostructures are highly stable and exhibited no sign of luminescence quenching or particle aggregation even after a storage of 30 months. Bactericidal effects of the nanostructures obtained from coconut shell is found to be relatively higher compared to those procured from wood. This variation in antibacterial performance of the samples is directly related to their morphological difference which in turn is heavily influenced by the precursor material used. MIC assay revealed that coconut shell derived graphene-tin oxide composite is able to inhibit the bacterial growth at a lower concentration (250 μg/mL) than the other nanostructures. Nanocomposites synthesized from agro-waste displayed significantly higher antimicrobial activity compared to the precursor and graphene oxide nanostructures thereby making them excellent candidates for various bactericidal applications such as disinfectants, sanitary agents etc.
Proposal of a rhombohedral-tetragonal phase composition for maximizing piezoelectricity of (K,Na)NbO3 ceramics
Authors: Lee Min-Ku , Yang Sun-A , Park Jin-Ju , Lee Gyoung-Ja 
Published: March 2019

AbstractGreat progress in the field of piezoelectricity of (K,Na)NbO3 (KNN) lead-free ceramics, driven by emerging rhombohedral-tetragonal (R-T) phase boundary, has instigated research activity regarding elaborate controls of the phase boundary structure. Through phase-microstructure-property mapping in KNN ceramics doped with Bi-containing perovskite oxides, in this study we for the first time report the existence of a certain R-T phase boundary state by which to create maximum piezoelectric response in KNN systems. This phase boundary condition is usually comprised of approximately 15% R phase and 85% T phase, regardless of the choice of dopant material. Any deviation from this phase composition, either by inclusion of orthorhombic (O) phase or by enrichment of R phase, has a negative effect on the value of d33. These findings can provide useful guidance for chemical doping control associated with the type of phase boundary and the phase composition for advanced KNN-based materials.
Volume unbalance on the 2016 Amatrice - Norcia (Central Italy) seismic sequence and insights on normal fault earthquake mechanism
Authors: Bignami Christian , Valerio Emanuela , Carminati Eugenio , Doglioni Carlo , Tizzani Pietro , Lanari Riccardo 
Published: March 2019

AbstractWe analyse the Mw 6.5, 2016 Amatrice-Norcia (Central Italy) seismic sequence by means of InSAR, GPS, seismological and geologic data. The >1000 km2 area affected by deformation is involving a volume of about 6000 km3 and the relocated seismicity is widely distributed in the hangingwall of the master fault system and the conjugate antithetic faults. Noteworthy, the coseismically subsided hangingwall volume is about 0.12 km3, whereas the uplifted adjacent volumes uplifted only 0.016 km3. Therefore, the subsided volume was about 7.5 times larger than the uplifted one. The coseismic motion requires equivalent volume at depth absorbing the hangingwall downward movement. This unbalance regularly occurs in normal fault-related earthquakes and can be inferred as a significant contribution to coseismic strain accomodated by a stress-drop driven collapse of precursory dilatancy. The vertical coseismic displacement is in fact larger than the horizontal component, consistent with the vertical orientation of the maximum lithostatic stress tensor.
HNF4α is a novel regulator of intestinal glucose-dependent insulinotropic polypeptide
Authors: Girard Romain , Darsigny Mathieu , Jones Christine , Maloum-Rami Faïza , Gélinas Yves , Carpentier André C. , Laplante Mathieu , Perreault Nathalie , Boudreau François 
Published: March 2019

AbstractMutations in the HNF4A gene cause MODY1 and are associated with an increased risk of Type 2 diabetes mellitus. On the other hand, incretins are hormones that potentiate reductions in blood glucose levels. Given the established role of incretin-based therapy to treat diabetes and metabolic disorders, we investigated a possible regulatory link between intestinal epithelial HNF4α and glucose-dependent insulinotropic polypeptide (GIP), an incretin that is specifically produced by gut enteroendocrine cells. Conditional deletion of HNF4α in the whole intestinal epithelium was achieved by crossing Villin-Cre and Hnf4αloxP/loxP C57BL/6 mouse models. GIP expression was measured by qPCR, immunofluorescence and ELISA. Gene transcription was assessed by luciferase and electrophoretic mobility shift assays. Metabolic parameters were analyzed by indirect calorimetry and dual-energy X-ray absorptiometry. HNF4α specific deletion in the intestine led to a reduction in GIP. HNF4α was able to positively control Gip transcriptional activity in collaboration with GATA-4 transcription factor. Glucose homeostasis and glucose-stimulated insulin secretion remained unchanged in HNF4α deficient mice. Changes in GIP production in these mice did not impact nutrition or energy metabolism under normal physiology but led to a reduction of bone area and mineral content, a well described physiological consequence of GIP deficiency. Our findings point to a novel regulatory role between intestinal HNF4α and GIP with possible functional impact on bone density.
Circumpolar permafrost maps and geohazard indices for near-future infrastructure risk assessments
Authors: Karjalainen Olli , Aalto Juha , Luoto Miska , Westermann Sebastian , Romanovsky Vladimir E. , Nelson Frederick E. , Etzelmüller Bernd , Hjort Jan 
Published: March 2019

AbstractOngoing climate change is causing fundamental changes in the Arctic, some of which can be hazardous to nature and human activity. In the context of Earth surface systems, warming climate may lead to rising ground temperatures and thaw of permafrost. This Data Descriptor presents circumpolar permafrost maps and geohazard indices depicting zones of varying potential for development of hazards related to near-surface permafrost degradation, such as ground subsidence. Statistical models were used to predict ground temperature and the thickness of the seasonally thawed (active) layer using geospatial data on environmental conditions at 30 arc-second resolution. These predictions, together with data on factors (ground ice content, soil grain size and slope gradient) affecting permafrost stability, were used to formulate geohazard indices. Using climate-forcing scenarios (Representative Concentration Pathways 2.6, 4.5 and 8.5), permafrost extent and hazard potential were projected for the 2041–2060 and 2061–2080 time periods. The resulting data (seven permafrost and 24 geohazard maps) are relevant to near-future infrastructure risk assessments and for targeting localized geohazard analyses.
The Subnational Human Development Database
Authors: Smits Jeroen , Permanyer Iñaki 
Published: March 2019

AbstractIn this paper we describe the Subnational Human Development Database. This database contains for the period 1990–2017 for 1625 regions within 161 countries the national and subnational values of the Subnational Human Development Index (SHDI), for the three dimension indices on the basis of which the SHDI is constructed – education, health and standard of living --, and for the four indicators needed to create the dimension indices -- expected years of schooling, mean years of schooling, life expectancy and gross national income per capita. The subnational values of the four indicators were computed using data from statistical offices and from the Area Database of the Global Data Lab, which contains indicators aggregated from household surveys and census datasets. Values for missing years were estimated by interpolation and extrapolation from real data. By normalizing the population-weighted averages of the indicators to their national levels in the UNDP-HDI database, values of the SHDI and its dimension indices were obtained that at national level equal their official versions of the UNDP.