bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of LXRα improves cardiac remodeling induced by pulmonary artery hypertension in rats
Authors: Gong Yibo , Yang Yifeng , Wu Qin , Gao Ge , Liu Yin , Xiong Yaoyao , Huang Can , Wu Sijie 
Published: July 2017

AbstractInflammatory factors regulated by NF-κB play a significant role in PAH and myocardial hypertrophy. LXR activation may inhibit myocardial hypertrophy via suppressing inflammatory pathways; it is unknown whether LXR is also involved in PAH-induced myocardial hypertrophy or remodeling. To further explore the protective effect of LXR in PAH-induced cardiac hypertrophy and remodeling, a PAH model was developed, and T0901317, an agonist of LXR, was used to examine the effect of LXR activation. PAH rats demonstrated obvious cardiac hypertrophy and remodeling in the right ventricle, but significant improvement of cardiac hypertrophy and remodeling was observed in PAH rats treated with T0901317. Through RT-PCR, Western blot and ELISA examination, NF-κB, IL-6, TNF-α, and iNOS were found to be significantly reduced in PAH rats treated with T0901317 compared to PAH rats treated with DMSO. Apoptosis was also significantly reduced in PAH rats treated with T0901317. Thus, LXR activation may inhibit PAH-induced cardiac hypertrophy and remodeling by inhibiting NF-κB-mediated inflammatory pathways.
Metabolomic characteristics of cholesterol-induced non-obese nonalcoholic fatty liver disease in mice
Authors: Tu Lan N. , Showalter Megan R. , Cajka Tomas , Fan Sili , Pillai Viju V. , Fiehn Oliver , Selvaraj Vimal 
Published: July 2017

AbstractNonalcoholic fatty liver disease (NAFLD) in non-obese patients remains a clinical condition with unclear etiology and pathogenesis. Using a metabolomics approach in a mouse model that recapitulates almost all the characteristic features of non-obese NAFLD, we aimed to advance mechanistic understanding of this disorder. Mice fed high fat, high cholesterol, cholate (HFHCC) diet for three weeks consistently developed hepatic pathology similar to NAFLD and nonalcoholic steatohepatitis (NASH) without changes to body weight or fat pad weights. Gas- and liquid chromatography/mass spectrometry-based profiling of lipidomic and primary metabolism changes in the liver and plasma revealed that systemic mechanisms leading to steatosis and hepatitis in this non-obese NAFLD model were driven by a combination of effects directed by elevated free cholesterol, cholesterol esters and cholic acid, and associated changes to metabolism of sphingomyelins and phosphatidylcholines. These results demonstrate that mechanisms underlying cholesterol-induced non-obese NAFLD are distinct from NAFLD occurring as a consequence of metabolic syndrome. In addition, this investigation provides one of the first metabolite reference profiles for interpreting effects of dietary and hepatic cholesterol in human non-obese NAFLD/NASH patients.
Structural determinants at the M2 muscarinic receptor modulate the RGS4-GIRK response to pilocarpine by impairment of the receptor voltage sensitivity
Authors: Chen I-Shan , Furutani Kazuharu , Kurachi Yoshihisa 
Published: July 2017

AbstractMembrane potential controls the response of the M2 muscarinic receptor to its ligands. Membrane hyperpolarization increases response to the full agonist acetylcholine (ACh) while decreasing response to the partial agonist pilocarpine. We previously have demonstrated that the regulator of G-protein signaling (RGS) 4 protein discriminates between the voltage-dependent responses of ACh and pilocarpine; however, the underlying mechanism remains unclear. Here we show that RGS4 is involved in the voltage-dependent behavior of the M2 muscarinic receptor-mediated signaling in response to pilocarpine. Additionally we revealed structural determinants on the M2 muscarinic receptor underlying the voltage-dependent response. By electrophysiological recording in Xenopus oocytes expressing M2 muscarinic receptor and G-protein-gated inwardly rectifying K+ channels, we quantified voltage-dependent desensitization of pilocarpine-induced current in the presence or absence of RGS4. Hyperpolarization-induced desensitization of the current required for RGS4, also depended on pilocarpine concentration. Mutations of charged residues in the aspartic acid-arginine-tyrosine motif of the M2 muscarinic receptor, but not intracellular loop 3, significantly impaired the voltage-dependence of RGS4 function. Thus, our results demonstrated that voltage-dependence of RGS4 modulation is derived from the M2 muscarinic receptor. These results provide novel insights into how membrane potential impacts G-protein signaling by modulating GPCR communication with downstream effectors.
Modulation of water diffusion by activation-induced neural cell swelling in Aplysia Californica
Authors: Abe Yoshifumi , Van Nguyen Khieu , Tsurugizawa Tomokazu , Ciobanu Luisa , Le Bihan Denis 
Published: July 2017

AbstractDiffusion functional magnetic resonance imaging (DfMRI) has been proposed as a method for functional neuroimaging studies, as an alternative to blood oxygenation level dependent (BOLD)-fMRI. DfMRI is thought to more directly reflect neural activation, but its exact mechanism remains unclear. It has been hypothesized that the water apparent diffusion coefficient (ADC) decrease observed upon neural activation results from swelling of neurons or neuron parts. To elucidate the origin of the DfMRI response at cellular level we performed diffusion MR microscopy at 17.2 T in Aplysia californica buccal ganglia and compared the water ADCs at cellular and ganglia levels before and after neuronal activation induced by perfusion with a solution containing dopamine. Neural cell swelling, evidenced from optical microscopy imaging, resulted in an intracellular ADC increase and an ADC decrease at ganglia level. Furthermore, the intracellular ADC increase was found to have a significant positive correlation with the increase in cell size. Our results strongly support the hypothesis that the ADC decrease observed with DfMRI upon neuronal activation at tissue level reflects activation-induced neural cell swelling.
Identification and analysis of mtDNA genomes attributed to Finns reveal long-stagnant demographic trends obscured in the total diversity
Authors: Översti Sanni , Onkamo Päivi , Stoljarova Monika , Budowle Bruce , Sajantila Antti , Palo Jukka U. 
Published: July 2017

AbstractIn Europe, modern mitochondrial diversity is relatively homogeneous and suggests an ubiquitous rapid population growth since the Neolithic revolution. Similar patterns also have been observed in mitochondrial control region data in Finland, which contrasts with the distinctive autosomal and Y-chromosomal diversity among Finns. A different picture emerges from the 843 whole mitochondrial genomes from modern Finns analyzed here. Up to one third of the subhaplogroups can be considered as Finn-characteristic, i.e. rather common in Finland but virtually absent or rare elsewhere in Europe. Bayesian phylogenetic analyses suggest that most of these attributed Finnish lineages date back to around 3,000–5,000 years, coinciding with the arrival of Corded Ware culture and agriculture into Finland. Bayesian estimation of past effective population sizes reveals two differing demographic histories: 1) the ‘local’ Finnish mtDNA haplotypes yielding small and dwindling size estimates for most of the past; and 2) the ‘immigrant’ haplotypes showing growth typical of most European populations. The results based on the local diversity are more in line with that known about Finns from other studies, e.g., Y-chromosome analyses and archaeology findings. The mitochondrial gene pool thus may contain signals of local population history that cannot be readily deduced from the total diversity.
Suppression of HBV replication by the expression of nickase- and nuclease dead-Cas9
Authors: Kurihara Takeshi , Fukuhara Takasuke , Ono Chikako , Yamamoto Satomi , Uemura Kentaro , Okamoto Toru , Sugiyama Masaya , Motooka Daisuke , Nakamura Shota , Ikawa Masato , Mizokami Masashi , Maehara Yoshihiko , Matsuura Yoshiharu 
Published: July 2017

AbstractComplete removal of hepatitis B virus (HBV) DNA from nuclei is difficult by the current therapies. Recent reports have shown that a novel genome-editing tool using Cas9 with a single-guide RNA (sgRNA) system can cleave the HBV genome in vitro and in vivo. However, induction of a double-strand break (DSB) on the targeted genome by Cas9 risks undesirable off-target cleavage on the host genome. Nickase-Cas9 cleaves a single strand of DNA, and thereby two sgRNAs are required for inducing DSBs. To avoid Cas9-induced off-target mutagenesis, we examined the effects of the expressions of nickase-Cas9 and nuclease dead Cas9 (d-Cas9) with sgRNAs on HBV replication. The expression of nickase-Cas9 with a pair of sgRNAs cleaved the target HBV genome and suppressed the viral-protein expression and HBV replication in vitro. Moreover, nickase-Cas9 with the sgRNA pair cleaved the targeted HBV genome in mouse liver. Interestingly, d-Cas9 expression with the sgRNAs also suppressed HBV replication in vitro without cleaving the HBV genome. These results suggest the possible use of nickase-Cas9 and d-Cas9 with a pair of sgRNAs for eliminating HBV DNA from the livers of chronic hepatitis B patients with low risk of undesirable off-target mutation on the host genome.
Crystal structure of a low molecular weight activator Blm-pep with yeast 20S proteasome – insights into the enzyme activation mechanism
Authors: Witkowska Julia , Giżyńska Małgorzata , Grudnik Przemysław , Golik Przemysław , Karpowicz Przemysław , Giełdoń Artur , Dubin Grzegorz , Jankowska Elżbieta 
Published: July 2017

AbstractProteasomes are responsible for protein turnover in eukaryotic cells, degrading short-lived species but also removing improperly folded or oxidatively damaged ones. Dysfunction of a proteasome results in gradual accumulation of misfolded/damaged proteins, leading to their aggregation. It has been postulated that proteasome activators may facilitate removal of such aggregation-prone proteins and thus prevent development of neurodegenerative disorders. However, the discovery of pharmacologically relevant compounds is hindered by insufficient structural understanding of the activation process. In this study we provide a model peptidic activator of human proteasome and analyze the structure-activity relationship within this novel scaffold. The binding mode of the activator at the relevant pocket within the proteasome has been determined by X-ray crystallography. This crystal structure provides an important basis for rational design of pharmacological compounds. Moreover, by providing a novel insight into the proteasome gating mechanism, our results allow the commonly accepted model of proteasome regulation to be revisited.
Capturing 3D Water Flow in Rooted Soil by Ultra-fast Neutron Tomography
Authors: Tötzke Christian , Kardjilov Nikolay , Manke Ingo , Oswald Sascha E. 
Published: July 2017

AbstractWater infiltration in soil is not only affected by the inherent heterogeneities of soil, but even more by the interaction with plant roots and their water uptake. Neutron tomography is a unique non-invasive 3D tool to visualize plant root systems together with the soil water distribution in situ. So far, acquisition times in the range of hours have been the major limitation for imaging 3D water dynamics. Implementing an alternative acquisition procedure we boosted the speed of acquisition capturing an entire tomogram within 10 s. This allows, for the first time, tracking of a water front ascending in a rooted soil column upon infiltration of deuterated water time-resolved in 3D. Image quality and resolution could be sustained to a level allowing for capturing the root system in high detail. Good signal-to-noise ratio and contrast were the key to visualize dynamic changes in water content and to localize the root uptake. We demonstrated the ability of ultra-fast tomography to quantitatively image quick changes of water content in the rhizosphere and outlined the value of such imaging data for 3D water uptake modelling. The presented method paves the way for time-resolved studies of various 3D flow and transport phenomena in porous systems.
Neurogenesis from Sox2 expressing cells in the adult cerebellar cortex
Authors: Ahlfeld Julia , Filser Severin , Schmidt Felix , Wefers Annika K. , Merk Daniel J. , Glaß Rainer , Herms Jochen , Schüller Ulrich 
Published: July 2017

AbstractWe identified a rare undifferentiated cell population that is intermingled with the Bergmann glia of the adult murine cerebellar cortex, expresses the stem cell markers Sox2 and Nestin, and lacks markers of glial or neuronal differentiation. Interestingly, such Sox2+ S100− cells of the adult cerebellum expanded after adequate physiological stimuli in mice (exercise), and Sox2+ precursors acquired positivity for the neuronal marker NeuN over time and integrated into cellular networks. In human patients, SOX2+ S100− cells similarly increased in number after relevant pathological insults (infarcts), suggesting a similar expansion of cells that lack terminal glial differentiation.
Machine Learning Model Analysis of Breeding Habitats for the Black-necked Crane in Central Asian Uplands under Anthropogenic Pressures
Authors: Han Xuesong , Guo Yumin , Mi Chunrong , Huettmann Falk , Wen Lijia 
Published: July 2017

AbstractThe black-necked crane (Grus nigricollis) is the only alpine crane species and is endemic to the Tibetan Plateau. The breeding habitats of this species are poorly understood, which greatly hampers practical research and conservation work. Using machine learning methods and the best-available data from our 7,000-kilometer mega-transect survey and open access data, we built the first species distribution model (SDM) to analyze the black-necked crane’s breeding habitats. Our model showed that current conservation gaps account for 26.7% of its predicted breeding habitats. Specifically, the northern parts of the Hengduan Mountains and the southeastern Tibet Valley, the northern side of the middle Kunlun Mountains, parts of the Pamir Plateau, the northern Pakistan Highlands and the western Hindu Kush should be considered as its main potential breeding areas. Additionally, our model suggested that the crane prefers to breed in alpine meadows at an elevation over 2,800 m, a maximum temperature of the warmest month below 20.5 °C, and a temperature seasonality above 7,800 units. The identified conservation gaps and potential breeding areas can aid in clearly prioritizing future conservation and research, but more attention and study should be directed to the unassessed Western Development of China to secure this endangered crane lineage and other wildlife on the Tibetan Plateau.
Discontinuous boundaries of slow slip events beneath the Bungo Channel, southwest Japan
Authors: Nakata Ryoko , Hino Hideitsu , Kuwatani Tatsu , Yoshioka Shoichi , Okada Masato , Hori Takane 
Published: July 2017

AbstractThe down-dip limit of the seismogenic zone and up-dip and down-dip limits of the deep low-frequency tremors in southwest Japan are clearly imaged by the hypocentre distribution. Previous studies using smooth constraints in inversion analyses estimated that long-term slow slip events (L-SSEs) beneath the Bungo Channel are distributed smoothly from the down-dip part of the seismogenic zone to the up-dip part of the tremors. Here, we use fused regularisation, a type of sparse modelling suitable for detecting discontinuous changes in the model parameters to estimate the slip distribution of L-SSEs. The largest slip abruptly becomes zero at the down-dip limit of the seismogenic zone, is immediately reduced to half at the up-dip limit of the tremors, and becomes zero near its down-dip limit. Such correspondences imply that some thresholds exist in the generation processes for both tremors and SSEs. Hence, geodetic data inversion with sparse modelling can detect such high resolution in the slip distribution.
Particle Adsorption on Hydrogel Surfaces in Aqueous Media due to van der Waals Attraction
Authors: Sato Naoko , Aoyama Yurina , Yamanaka Junpei , Toyotama Akiko , Okuzono Tohru 
Published: July 2017

AbstractParticle adhesion onto hydrogels has recently attracted considerable attention because of the potential biomedical applications of the resultant materials. A variety of interactions have been taken advantage of for adsorption, including electrostatic forces, hydrophobic interactions and hydrogen bonding. In this study, we report significant adsorption of submicron-sized silica particles onto hydrogel surfaces in water, purely by van der Waals (vdW) attraction. The vdW forces enabled strong adhesions between dielectric materials in air. However, because the Hamaker constant decreases in water typically by a factor of approximately 1/100, it is not clear whether vdW attraction is the major driving force in aqueous settings. We investigated the adsorption of silica particles (diameter = 25–600 nm) on poly(acrylamide) and poly(dimethylacrylamide) gels using optical microscopy, under conditions where chemical and electrostatic adsorption is negligible. The quantity of adsorbed particles decreased on decreasing the Hamaker constant by varying the refractive indices of the particles and medium (ethyleneglycol/water), indicating that the adsorption is because of the vdW forces. The adsorption isotherm was discussed based on the adhesive contact model in consideration of the deformation of the gel surface. The present findings will advance the elucidation and development of adsorption in various types of soft materials.
3D anatomical and perfusion MRI for longitudinal evaluation of biomaterials for bone regeneration of femoral bone defect in rats
Authors: Ribot Emeline J. , Tournier Clement , Aid-Launais Rachida , Koonjoo Neha , Oliveira Hugo , Trotier Aurelien J. , Rey Sylvie , Wecker Didier , Letourneur Didier , Amedee Vilamitjana Joelle , Miraux Sylvain 
Published: July 2017

AbstractMagnetic Resonance Imaging (MRI) appears as a good surrogate to Computed Tomography (CT) scan as it does not involve radiation. In this context, a 3D anatomical and perfusion MR imaging protocol was developed to follow the evolution of bone regeneration and the neo-vascularization in femoral bone defects in rats. For this, three different biomaterials based on Pullulan-Dextran and containing either Fucoidan or HydroxyApatite or both were implanted. In vivo MRI, ex vivo micro-CT and histology were performed 1, 3 and 5 weeks after implantation. The high spatially resolved (156 × 182 × 195 µm) anatomical images showed a high contrast from the defects filled with biomaterials that decreased over time due to bone formation. The 3D Dynamic Contrast Enhanced (DCE) imaging with high temporal resolution (1 image/19 s) enabled to detect a modification in the Area-Under-The-Gadolinium-Curve over the weeks post implantation. The high sensitivity of MRI enabled to distinguish which biomaterial was the least efficient for bone regeneration, which was confirmed by micro-CT images and by a lower vessel density observed by histology. In conclusion, the methodology developed here highlights the efficiency of longitudinal MRI for tissue engineering as a routine small animal exam.
The N-terminal dimerization is required for TDP-43 splicing activity
Authors: Jiang Lei-Lei , Xue Wei , Hong Jun-Ye , Zhang Jun-Ting , Li Min-Jun , Yu Shao-Ning , He Jian-Hua , Hu Hong-Yu 
Published: July 2017

AbstractTDP-43 is a nuclear factor that functions in promoting pre-mRNA splicing. Deletion of the N-terminal domain (NTD) and nuclear localization signal (NLS) (i.e., TDP-35) results in mislocalization to cytoplasm and formation of inclusions. However, how the NTD functions in TDP-43 activity and proteinopathy remains largely unknown. Here, we studied the structure and function of the NTD in inclusion formation and pre-mRNA splicing of TDP-43 by using biochemical and biophysical approaches. We found that TDP-43 NTD forms a homodimer in solution in a concentration-dependent manner, and formation of intermolecular disulfide results in further tetramerization. Based on the NMR structure of TDP-43 NTD, the dimerization interface centered on Leu71 and Val72 around the β7-strand was defined by mutagenesis and size-exclusion chromatography. Cell experiments revealed that the N-terminal dimerization plays roles in protecting TDP-43 against formation of cytoplasmic inclusions and enhancing pre-mRNA splicing activity of TDP-43 in nucleus. This study may provide mechanistic insights into the physiological function of TDP-43 and its related proteinopathies.
Emergence of hysteresis loop in social contagions on complex networks
Authors: Su Zhen , Wang Wei , Li Lixiang , Xiao Jinghua , Stanley H. Eugene 
Published: July 2017

AbstractUnderstanding the spreading mechanisms of social contagions in complex network systems has attracted much attention in the physics community. Here we propose a generalized threshold model to describe social contagions. Using extensive numerical simulations and theoretical analyses, we find that a hysteresis loop emerges in the system. Specifically, the steady state of the system is sensitive to the initial conditions of the dynamics of the system. In the steady state, the adoption size increases discontinuously with the transmission probability of information about social contagions, and trial size exhibits a non-monotonic pattern, i.e., it first increases discontinuously then decreases continuously. Finally we study social contagions on heterogeneous networks and find that network topology does not qualitatively affect our results.
After infection with Leishmania infantum, Golden Hamsters (Mesocricetus auratus) become more attractive to female sand flies (Lutzomyia longipalpis)
Authors: Nevatte T. M. , Ward R. D. , Sedda L. , Hamilton J. G. C. 
Published: July 2017

AbstractIn Brazil, human and canine visceral leishmaniasis is caused by infection with Leishmania infantum, a Protist parasite transmitted by blood-feeding female Lutzomyia longipalpis sand flies. The objective of this study was to determine if the odour of hamsters, infected with Le. infantum, was more attractive than the odour of the same hamsters, before they were infected. The attractiveness of odour collected from individual hamsters (n = 13), before they were infected, was compared in a longitudinal study, with the attractiveness of the odour of the same hamster in a Y-tube olfactometer bioassay, at a late stage of infection. The odour of six of the golden hamsters was significantly more attractive to 50% of the female sand flies at the end of infection compared to before infection and the odour of four of the golden hamsters was significantly more attractive to 75% of the female sand flies at the end of infection. These results strongly indicate that hamsters infected with Le. infantum become significantly more attractive to a greater proportion of female sand flies as the infection progresses.