bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wolves contribute to disease control in a multi-host system
Authors: Tanner E. , White A. , Acevedo P. , Balseiro A. , Marcos J. , Gortázar C. 
Published: May 2019

AbstractWe combine model results with field data for a system of wolves (Canis lupus) that prey on wild boar (Sus scrofa), a wildlife reservoir of tuberculosis, to examine how predation may contribute to disease control in multi-host systems. Results show that predation can lead to a marked reduction in the prevalence of infection without leading to a reduction in host population density since mortality due to predation can be compensated by a reduction in disease induced mortality. A key finding therefore is that a population that harbours a virulent infection can be regulated at a similar density by disease at high prevalence or by predation at low prevalence. Predators may therefore provide a key ecosystem service which should be recognised when considering human-carnivore conflicts and the conservation and re-establishment of carnivore populations.
Cynomolgus macaque IL37 polymorphism and control of SIV infection
Authors: Shiina Takashi , Suzuki Shingo , Congy-Jolivet Nicolas , Aarnink Alice , Garchon Henri-Jean , Dereuddre-Bosquet Nathalie , Vaslin Bruno , Tchitchek Nicolas , Desjardins Delphine , Autran Brigitte , Lambotte Olivier , Theodorou Ioannis , Le Grand Roger , Blancher Antoine 
Published: May 2019

AbstractThe association between gene polymorphisms and plasma virus load at the set point (SP-PVL) was investigated in Mauritian macaques inoculated with SIV. Among 44 macaques inoculated with 50 AID50, six individuals were selected: three with SP-PVL among the highest and three with SP-PVL among the lowest. The exons of 390 candidate genes of these six animals were sequenced. Twelve non-synonymous single nucleotide polymorphisms (NS-SNPs) lying in nine genes potentially associated with PVL were genotyped in 23 animals. Three NS-SNPs with probabilities of association with PVL less than 0.05 were genotyped in a total of 44 animals. One NS-SNP lying in exon 1 of the IL37 gene displayed a significant association (p = 3.33 × 10−4) and a strong odds ratio (19.52). Multiple linear regression modeling revealed three significant predictors of SP-PVL, including the IL37 exon 1 NS-SNP (p = 0.0004) and the MHC Class IB haplotypes M2 (p = 0.0007) and M6 (p = 0.0013). These three factors in conjunction explained 48% of the PVL variance (p = 4.8 × 10−6). The potential role of IL37 in the control of SIV infection is discussed.
Early exhumation of the Frontal Cordillera (Southern Central Andes) and implications for Andean mountain-building at ~33.5°S
Authors: Riesner Magali , Simoes Martine , Carrizo Daniel , Lacassin Robin 
Published: May 2019

AbstractThe Andes are the modern active example of a Cordilleran-type orogen, with mountain-building and crustal thickening within the upper plate of a subduction zone. Despite numerous studies of this emblematic mountain range, several primary traits of this orogeny remain unresolved or poorly documented. The onset of uplift and deformation of the Frontal Cordillera basement culmination of the Southern Central Andes is such an example, even though this structural unit appears as a first-order topographic and geological feature. To solve for this, new (U-Th)/He ages on apatite and zircon from granitoids of the Frontal Cordillera at ~33.5°S are provided here. These data, interpreted as an age-elevation thermochronological profile, imply continuous exhumation initiating well before ~12–14 Ma, and at most by ~22 Ma when considering the youngest zircon grain from the lowermost sample. The age of exhumation onset is then refined to ~20 Ma by combining these results with data on sedimentary provenance from the nearby basins. Such continuous exhumation since ~20 Ma needs to have been sustained by tectonic uplift on an underlying crustal-scale thrust ramp. Such early exhumation and associated uplift of the Frontal Cordillera invalidate the classically proposed east-vergent models of the Andes at this latitude. Additionally, they provide further support to recent views on Andean mountain-building proposing that the Andes at ~33.5°S grew firstly over west-vergent basement structures.
Sperm motility of oysters from distinct populations differs in response to ocean acidification and freshening
Authors: Falkenberg Laura J. , Styan Craig A. , Havenhand Jon N. 
Published: May 2019

AbstractSpecies’ responses to climate change will reflect variability in the effects of physiological selection that future conditions impose. Here, we considered the effects of ocean acidification (increases in pCO2; 606, 925, 1250 µatm) and freshening (reductions in salinity; 33, 23, 13 PSU) on sperm motility in oysters (Crassostrea gigas) from two populations (one recently invaded, one established for 60+ years). Freshening reduced sperm motility in the established population, but this was offset by a positive effect of acidification. Freshening also reduced sperm motility in the recently invaded population, but acidification had no effect. Response direction, strength, and variance differed among individuals within each population. For the established population, freshening increased variance in sperm motility, and exposure to both acidification and freshening modified the performance rank of males (i.e. rank motility of sperm). In contrast, for the recently invaded population, freshening caused a smaller change in variance, and male performance rank was broadly consistent across treatments. That inter-population differences in response may be related to environmental history (recently invaded, or established), indicates this could influence scope for selection and adaptation. These results highlight the need to consider variation within and among population responses to forecast effects of multiple environmental change drivers.
Multimodal Wrist Biosensor for Wearable Cuff-less Blood Pressure Monitoring System
Authors: Rachim Vega Pradana , Chung Wan-Young 
Published: May 2019

AbstractWe propose a multimodal biosensor for use in continuous blood pressure (BP) monitoring system. Our proposed novel configuration measures photo-plethysmography (PPG) and impedance plethysmography (IPG) signals simultaneously from the subject wrist. The proposed biosensor system enables a fully non-intrusive system that is cuff-less, also utilize a single measurement site for maximum wearability and convenience of the patients. The efficacy of the proposed technique was evaluated on 10 young healthy subjects. Experimental results indicate that the pulse transit time (PTT)-based features calculated from an IPG peak and PPG maximum second derivative (f14) had a relatively high correlation coefficient (r) to the reference BP, with −0.81 ± 0.08 and −0.78 ± 0.09 for systolic BP (SBP) and diastolic BP (DBP), respectively. Moreover, here we proposed two BP estimation models that utilize six- and one-point calibration models. The six-point model is based on the PTT, whereas the one-point model is based on the combined PTT and radial impedance (Z). Thus, in both models, we observed an adequate root-mean-square-error estimation performance, with 4.20 ± 1.66 and 2.90 ± 0.90 for SBP and DBP, respectively, with the PTT BP model; and 6.86 ± 1.65 and 6.67 ± 1.75 for SBP and DBP, respectively, with the PTT-Z BP model. This study suggests the possibility of estimating a subject’s BP from only wrist bio-signals. Thus, the six- and one-point PTT-Z calibration models offer adequate performance for practical applications.
RETRACTED ARTICLE: The Adipocyte Na/K-ATPase Oxidant Amplification Loop is the Central Regulator of Western Diet-Induced Obesity and Associated Comorbidities
Authors: Pratt Rebecca D. , Brickman Cameron , Nawab Athar , Cottrill Cameron , Snoad Brian , Lakhani Hari Vishal , Jelcick Austin , Henderson Brandon , Bhardwaj Niharika N. , Sanabria Juan R. , Liu Jiang , Xie Zijian , Abraham Nader G. , Shapiro Joseph I. , Sodhi Komal 
Published: May 2019

AbstractObesity has become a worldwide epidemic. We have previously reported that systemic administration of pNaKtide which targets the Na/K-ATPase oxidant amplification loop (NKAL) was able to decrease systemic oxidative stress and adiposity in mice fed a high fat and fructose supplemented western diet (WD). As adipocytes are believed to play a central role in the development of obesity and its related comorbidities, we examined whether lentiviral-mediated adipocyte-specific expression of NaKtide, a peptide derived from the N domain of the alpha1 Na/K-ATPase subunit, could ameliorate the effects of the WD. C57BL6 mice were fed a WD, which activated Na/K-ATPase signaling in the adipocytes and induced an obese phenotype and caused an increase in plasma levels of leptin, IL-6 and TNFα. WD also decreased locomotor activity, expression of the D2 receptor and tyrosine hydroxylase in brain tissue, while markers of neurodegeneration and neuronal apoptosis were increased following the WD. Selective adipocyte expression of NaKtide in these mice fed a WD attenuated all of these changes including the brain biochemical alterations and behavioral adaptations. These data suggest that adipocyte derived cytokines play an essential role in the development of obesity induced by a WD and that targeting the adipocyte NKAL loop may serve as an effective therapeutic strategy.
An electrochemiluminescence based assay for quantitative detection of endogenous and exogenously applied MeCP2 protein variants
Authors: Steinkellner Hannes , Schönegger Anna , Etzler Julia , Kempaiah Prakasha , Huber Anna , Hahn Kathrin , Rose Katrin , Duerr Mark , Christodoulou John , Beribisky Alexander V. , Neuhaus Winfried , Laccone Franco 
Published: May 2019

AbstractMethyl-CpG-binding protein 2 (MeCP2) is a multifunctional chromosomal protein that plays a key role in the central nervous system. Its levels need to be tightly regulated, as both deficiency and excess of the protein can lead to severe neuronal dysfunction. Loss-of-function mutations affecting MeCP2 are the primary cause of Rett syndrome (RTT), a severe neurological disorder that is thought to result from absence of functional protein in the brain. Several therapeutic strategies for the treatment of RTT are currently being developed. One of them is the use of stable and native TAT-MeCP2 fusion proteins to replenish its levels in neurons after permeation across the blood-brain barrier (BBB). Here we describe the expression and purification of various transactivator of transcription (TAT)-MeCP2 variants and the development of an electrochemiluminescence based assay (ECLIA) that is able to measure endogenous MeCP2 and recombinant TAT-MeCP2 fusion protein levels in a 96-well plate format. The MeCP2 ECLIA produces highly quantitative, accurate and reproducible measurements with low intra- and inter-assay error throughout a wide working range. To underline its broad applicability, this assay was used to analyze brain tissue and study the transport of TAT-MeCP2 variants across an in vitro model of the blood-brain barrier.
A structural and biochemical comparison of Ribonuclease E homologues from pathogenic bacteria highlights species-specific properties
Authors: Mardle Charlotte E. , Shakespeare Thomas J. , Butt Louise E. , Goddard Layla R. , Gowers Darren M. , Atkins Helen S. , Vincent Helen A. , Callaghan Anastasia J. 
Published: May 2019

AbstractRegulation of gene expression through processing and turnover of RNA is a key mechanism that allows bacteria to rapidly adapt to changing environmental conditions. Consequently, RNA degrading enzymes (ribonucleases; RNases) such as the endoribonuclease RNase E, frequently play critical roles in pathogenic bacterial virulence and are potential antibacterial targets. RNase E consists of a highly conserved catalytic domain and a variable non-catalytic domain that functions as the structural scaffold for the multienzyme degradosome complex. Despite conservation of the catalytic domain, a recent study identified differences in the response of RNase E homologues from different species to the same inhibitory compound(s). While RNase E from Escherichia coli has been well-characterised, far less is known about RNase E homologues from other bacterial species. In this study, we structurally and biochemically characterise the RNase E catalytic domains from four pathogenic bacteria: Yersinia pestis, Francisella tularensis, Burkholderia pseudomallei and Acinetobacter baumannii, with a view to exploiting RNase E as an antibacterial target. Bioinformatics, small-angle x-ray scattering and biochemical RNA cleavage assays reveal globally similar structural and catalytic properties. Surprisingly, subtle species-specific differences in both structure and substrate specificity were also identified that may be important for the development of effective antibacterial drugs targeting RNase E.
Cytotoxicity of trifluridine correlates with the thymidine kinase 1 expression level
Authors: Kataoka Yuki , Iimori Makoto , Niimi Shinichiro , Tsukihara Hiroshi , Wakasa Takeshi , Saeki Hiroshi , Oki Eiji , Maehara Yoshihiko , Kitao Hiroyuki 
Published: May 2019

AbstractTrifluridine (FTD), a tri-fluorinated thymidine analogue, is a key component of the oral antitumor drug FTD/TPI (also known as TAS-102), which is used to treat refractory metastatic colorectal cancer. Thymidine kinase 1 (TK1) is thought to be important for the incorporation of FTD into DNA, resulting in DNA dysfunction and cytotoxicity. However, it remains unknown whether TK1 is essential for FTD incorporation into DNA and whether this event is affected by the expression level of TK1 because TK1-specific-deficient human cancer cell lines have not been established. Here, we generated TK1-knock-out human colorectal cancer cells using the CRISPR/Cas9 genome editing system and validated the specificity of TK1 knock-out by measuring expression of AFMID, which is encoded on the same locus as TK1. Using TK1-knock-out cells, we confirmed that TK1 is essential for cellular sensitivity to FTD. Furthermore, we demonstrated a correlation between the TK1 expression level and cytotoxicity of FTD using cells with inducible TK1 expression, which were generated from TK1-knock-out cells. Based on our finding that the TK1 expression level correlates with sensitivity to FTD, we suggest that FTD/TPI might efficiently treat cancers with high TK1 expression.
New PCR primers for metabarcoding environmental DNA from freshwater eels, genus Anguilla
Authors: Takeuchi Aya , Sado Tetsuya , Gotoh Ryo O. , Watanabe Shun , Tsukamoto Katsumi , Miya Masaki 
Published: May 2019

AbstractFreshwater eels of the genus Anguilla comprise 16 species that include three subspecies and are characterized by their unique catadromous life cycles. Their life histories and nocturnal life styles make it difficult to observe them in freshwater and marine habitats. To investigate their distribution and ecology in aquatic environments, we developed new PCR primers for metabarcoding environmental DNA (eDNA) from Anguilla. The new primers (MiEel) were designed for two conserved regions of the mitochondrial ATP6 gene, which amplify a variable region with sufficient interspecific variations ranging from five to 22 nucleotide differences (one to three nucleotide differences between three subspecies pairs). We confirmed the versatility of the MiEel primers for all freshwater eels using tissue DNA extracts when analyzed separately. The metabarcoding combined with the MiEel primers using mock communities enabled simultaneous detection of Anguilla at the species level. Analysis of eDNA samples from aquarium tanks, a controlled pond and natural rivers demonstrated that the MiEel metabarcoding could successfully detect the correct Anguilla species from water samples. These results suggested that eDNA metabarcoding with MiEel primers would be useful for non-invasively monitoring the presence of the endangered anguillid eels in aquatic environments where sampling surveys are difficult.
Comparative genomics approach to build a genome-wide database of high-quality, informative microsatellite markers: application on Phytophthora sojae, a soybean pathogen
Authors: Cai Guohong , Fleury Tomara J. , Zhang Ning 
Published: May 2019

AbstractMicrosatellites are a tract of repetitive, short DNA motifs (usually 1 to 6 bp) abundant in eukaryotic genomes. They are robust molecular markers in many areas of studies. Development of microsatellite markers usually involves three steps: (1) obtaining microsatellite-containing sequences, (2) primer design, and (3) screening microsatellite loci for polymorphism. The first and third steps require considerable resources. Next generation sequencing technologies have greatly alleviated the constraint of the first step. In this study, we leveraged the availability of genome assemblies of multiple individuals in many species and designed a comparative genomics approach to bioinformatically identify polymorphic loci. Our approach can eliminate or greatly reduce the need of experimental screening for polymorphism and ensure that the flanking regions do not have length difference that would confound interpretation of genotyping results using microsatellite markers. We applied this approach onPhytophthora sojae, a soybean pathogen, and identified 157 high-quality, informative microsatellite markers in this oomycete. Experimental validation of 20 loci supported bioinformatics predictions. Our approach can be readily applied to other organisms of which the genomes of multiple individuals have been sequenced.
RNA-seq analysis and fluorescence imaging of melon powdery mildew disease reveal an orchestrated reprogramming of host physiology
Authors: Polonio Álvaro , Pineda Mónica , Bautista Rocío , Martínez-Cruz Jesús , Pérez-Bueno María Luisa , Barón Matilde , Pérez-García Alejandro 
Published: May 2019

AbstractThe cucurbit powdery mildew elicited by Podosphaera xanthii is one of the most important limiting factors in cucurbit production. Our knowledge of the genetic and molecular bases underlying the physiological processes governing this disease is very limited. We used RNA-sequencing to identify differentially expressed genes in leaves of Cucumis melo upon inoculation with P. xanthii, using RNA samples obtained at different time points during the early stages of infection and their corresponding uninfected controls. In parallel, melon plants were phenotypically characterized using imaging techniques. We found a high number of differentially expressed genes (DEGs) in infected plants, which allowed for the identification of many plant processes that were dysregulated by the infection. Among those, genes involved in photosynthesis and related processes were found to be upregulated, whereas genes involved in secondary metabolism pathways, such as phenylpropanoid biosynthesis, were downregulated. These changes in gene expression could be functionally validated by chlorophyll fluorescence imaging and blue-green fluorescence imaging analyses, which corroborated the alterations in photosynthetic activity and the suppression of phenolic compound biosynthesis. The powdery mildew disease in melon is a consequence of a complex and multifaceted process that involves the dysregulation of many plant pathways such as primary and secondary metabolism.
Deciphering host lysosome-mediated elimination of Plasmodium berghei liver stage parasites
Authors: Niklaus L. , Agop-Nersesian C. , Schmuckli-Maurer J. , Wacker R. , Grünig V. , Heussler V. T. 
Published: May 2019

AbstractLiver stage Plasmodium parasites reside in a parasitophorous vacuole (PV) that associates with lysosomes. It has previously been shown that these organelles can have beneficial as well as harmful effects on the parasite. Yet it is not clear how the association of lysosomes with the parasite is controlled and how interactions with these organelles lead to the antagonistic outcomes. In this study we used advanced imaging techniques to characterize lysosomal interactions with the PV. In host cells harboring successfully developing parasites we observed that these interaction events reach an equilibrium at the PV membrane (PVM). In a population of arrested parasites, this equilibrium appeared to shift towards a strongly increased lysosomal fusion with the PVM witnessed by strong PVM labeling with the lysosomal marker protein LAMP1. This was followed by acidification of the PV and elimination of the parasite. To systematically investigate elimination of arrested parasites, we generated transgenic parasites that express the photosensitizer KillerRed, which leads to parasite killing after activation. Our work provides insights in cellular details of intracellular killing and lysosomal elimination of Plasmodium parasites independent of cells of the immune system.
Encapsulation of a TRPM8 Agonist, WS12, in Lipid Nanocapsules Potentiates PC3 Prostate Cancer Cell Migration Inhibition through Channel Activation
Authors: Grolez G. P. , Hammadi M. , Barras A. , Gordienko D. , Slomianny C. , Völkel P. , Angrand P. O. , Pinault M. , Guimaraes C. , Potier-Cartereau M. , Prevarskaya N. , Boukherroub R. , Gkika D. 
Published: May 2019

AbstractIn prostate carcinogenesis, expression and/or activation of the Transient Receptor Potential Melastatin 8 channel (TRPM8) was shown to block in vitro Prostate Cancer (PCa) cell migration. Because of their localization at the plasma membrane, ion channels, such as TRPM8 and other membrane receptors, are promising pharmacological targets. The aim of this study was thus to use nanocarriers encapsulating a TRPM8 agonist to efficiently activate the channel and therefore arrest PCa cell migration. To achieve this goal, the most efficient TRPM8 agonist, WS12, was encapsulated into Lipid NanoCapsules (LNC). The effect of the nanocarriers on channel activity and cellular physiological processes, such as cell viability and migration, were evaluated in vitro and in vivo. These results provide a proof-of-concept support for using TRPM8 channel-targeting nanotechnologies based on LNC to develop more effective methods inhibiting PCa cell migration in zebrafish xenograft.
Stable and manipulable Bloch point
Authors: Beg Marijan , Pepper Ryan A. , Cortés-Ortuño David , Atie Bilal , Bisotti Marc-Antonio , Downing Gary , Kluyver Thomas , Hovorka Ondrej , Fangohr Hans 
Published: May 2019

AbstractThe prediction of magnetic skyrmions being used to change the way we store and process data has led to materials with Dzyaloshinskii-Moriya interaction coming into the focus of intensive research. So far, studies have looked mostly at magnetic systems composed of materials with single chirality. In a search for potential future spintronic devices, combination of materials with different chirality into a single system may represent an important new avenue for research. Using finite element micromagnetic simulations, we study an FeGe disk with two layers of different chirality. We show that for particular thicknesses of layers, a stable Bloch point emerges at the interface between two layers. In addition, we demonstrate that the system undergoes hysteretic behaviour and that two different types of Bloch point exist. These ‘head-to-head’ and ‘tail-to-tail’ Bloch point configurations can, with the application of an external magnetic field, be switched between. Finally, by investigating the time evolution of the magnetisation field, we reveal the creation mechanism of the Bloch point. Our results introduce a stable and manipulable Bloch point to the collection of particle-like state candidates for the development of future spintronic devices.