bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective inhibition of mitochondrial sodium-calcium exchanger protects striatal neurons from α-synuclein plus rotenone induced toxicity
Authors: Bastioli Guendalina , Piccirillo Silvia , Castaldo Pasqualina , Magi Simona , Tozzi Alessandro , Amoroso Salvatore , Calabresi Paolo 
Published: January 2019

AbstractProgressive accumulation of α-synuclein (α-syn) and exposure to environmental toxins are risk factors that may both concur to Parkinson’s disease (PD) pathogenesis. Electrophysiological recordings of field postsynaptic potentials (fEPSPs) and Ca2+measures in striatal brain slices and differentiated SH-SY5Y cells showed that co-application of α-syn and the neurotoxic pesticide rotenone (Rot) induced Ca2+dysregulation and alteration of both synaptic transmission and cell function. Interestingly, the presence of the mitochondrial NCX inhibitor CGP-37157 prevented these alterations. The specific involvement of the mitochondrial NCX was confirmed by the inability of the plasma membrane inhibitor SN-6 to counteract such phenomenon. Of note, using a siRNA approach, we found that NCX1 was the isoform specifically involved. These findings suggested that NCX1, operating on the mitochondrial membrane, may have a critical role in the maintenance of ionic Ca2+homeostasis in PD and that its inhibition most likely exerts a protective effect in the toxicity induced by α-syn and Rot.
Decreased IL-17RB expression impairs CD11b+CD11c− myeloid cell accumulation in gastric mucosa and host defense during the early-phase of Helicobacter pylori infection
Authors: Teng Yong-sheng , Liu Yu-gang , Chen Xian-hua , Wang Ting-ting , Cheng Ping , Lv Yi-pin , Kong Hui , Mao Fang-yuan , Hao Chuan-jie , Yang Shi-ming , Chen Weisan , Zhang Jin-yu , Peng Liu-sheng , Han Bin , Ma Qiang , Han Jia , Zou Quan-ming , Zhuang Yuan 
Published: January 2019

AbstractInterleukin-17 receptor B (IL-17RB), a member of the IL-17 receptor family activated by IL-17B/IL-17E, has been shown to be involved in inflammatory diseases. However, the regulation and function of IL-17RB in Helicobacter pylori (H. pylori) infection, especially in the early-phase is still unknown. Here, we found that gastric IL-17RB mRNA and protein were decreased in gastric mucosa of both patients and mice infected with H. pylori. In vitro experiments show that IL-17RB expression was down regulated via PI3K/AKT pathway on gastric epithelial cells (GECs) stimulated with H. pylori in a cagA-involved manner, while in vivo studies showed that the effect was partially dependent on cagA expression. IL-17E was also decreased during the early-phase of H. pylori infection, and provision of exogenous IL-17E resulted in increased CD11b+CD11c− myeloid cells accumulation and decreased bacteria colonization within the gastric mucosa. In the early-phase of H. pylori infection, IL-17E-IL-17RB promoted gastric epithelial cell-derived CXCL1/2/5/6 to attract CD11b+CD11c− myeloid cells, and also contributed to host defense by promoting the production of antibacterial protein Reg3a. This study defines a negative regulatory network involving IL-17E, GECs, IL-17RB, CD11b+CD11c− myeloid cells, and Reg3a in the early-phase of H. pylori infection, which results in an impaired host defense within the gastric microenvironment, suggesting IL-17RB as a potential early intervening target in H. pylori infection.
Induction of 3-hydroxy-3-methylglutaryl-CoA reductase mediates statin resistance in breast cancer cells
Authors: Göbel Andy , Breining Dorit , Rauner Martina , Hofbauer Lorenz C. , Rachner Tilman D. 
Published: January 2019

AbstractThe mevalonate pathway has emerged as a promising target for several solid tumors. Statins are inhibitors of the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the rate-limiting enzyme of this pathway, and are commonly used to treat patients with hypercholesterolemia. Pleiotropic antitumor mechanisms of statins have been demonstrated for several human cancer types. However, cancer cells differ in their individual statin sensitivity and some cell lines have shown relative resistance. In this study we demonstrate, that the human breast cancer cell lines MDA-MB-231, MDA-MB-468, MCF-7, and T47D are differentially affected by statins. Whereas the vitality of MDA-MB-231 and MDA-MB-468 cells was reduced by up to 60% using atorvastatin, simvastatin, or rosuvastatin (p < 0.001), only marginal effects were seen in T47D and MCF-7 cells following exposure to statins. Statin treatment led to an upregulation of HMGCR mRNA and protein expression by up to sixfolds in the statin-resistant cells lines (p < 0.001), but no alterations of HMGCR were observed in the statin-sensitive MDA-MB-231 and MDA-MB-468 cells. The knockdown of HMGCR prior to statin treatment sensitized the resistant cell lines, reflected by a 70% reduction in vitality, increased apoptotic DNA fragmentation (sixfold) and by accumulation of the apoptosis marker cleaved poly-ADP ribose polymerase. Statins induced a cleavage of the sterol-regulatory element-binding protein (SREBP)-2, a transcriptional activator of the HMGCR, in T47D and MCF-7 cells. The inhibition of SREBP-2 activation by co-administration of dipyridamole sensitized MCF-7 and T47D cells for statins (loss of vitality by 80%; p < 0.001). Furthermore, assessment of a statin-resistant MDA-MB-231 clone, generated by long-term sublethal statin exposure, revealed a significant induction of HMGCR expression by up to 12-folds (p < 0.001). Knockdown of HMGCR restored statin sensitivity back to levels of the parental cells. In conclusion, these results indicate a resistance of cancer cells against statins, which is in part due to the induction of HMGCR.
Amide nitrogen pyramidalization changes lactam amide spinning
Authors: Otani Yuko , Liu Xin , Ohno Hisashi , Wang Siyuan , Zhai Luhan , Su Aoze , Kawahata Masatoshi , Yamaguchi Kentaro , Ohwada Tomohiko 
Published: January 2019

AbstractAlthough cis-trans lactam amide rotation is fundamentally important, it has been little studied, except for a report on peptide-based lactams. Here, we find a consistent relationship between the lactam amide cis/trans ratios and the rotation rates between the trans and cis lactam amides upon the lactam chain length of the stapling side-chain of two 7-azabicyclo[2.2.1]heptane bicyclic units, linked through a non-planar amide bond. That is, as the chain length increased, the rotational rate of trans to cis lactam amide was decreased, and consequently the trans ratio was increased. This chain length-dependency of the lactam amide isomerization and our simulation studies support the idea that the present lactam amides can spin through 360 degrees as in open-chain amides, due to the occurrence of nitrogen pyramidalization. The tilting direction of the pyramidal amide nitrogen atom of the bicyclic systems is synchronized with the direction of the semicircle-rotation of the amide.
Venous identity requires BMP signalling through ALK3
Authors: Neal Alice , Nornes Svanhild , Payne Sophie , Wallace Marsha D. , Fritzsche Martin , Louphrasitthiphol Pakavarin , Wilkinson Robert N. , Chouliaras Kira M. , Liu Ke , Plant Karen , Sholapurkar Radhika , Ratnayaka Indrika , Herzog Wiebke , Bond Gareth , Chico Tim , Bou-Gharios George , De Val Sarah 
Published: January 2019

AbstractVenous endothelial cells are molecularly and functionally distinct from their arterial counterparts. Although veins are often considered the default endothelial state, genetic manipulations can modulate both acquisition and loss of venous fate, suggesting that venous identity is the result of active transcriptional regulation. However, little is known about this process. Here we show that BMP signalling controls venous identity via the ALK3/BMPR1A receptor and SMAD1/SMAD5. Perturbations to TGF-β and BMP signalling in mice and zebrafish result in aberrant vein formation and loss of expression of the venous-specific gene Ephb4, with no effect on arterial identity. Analysis of a venous endothelium-specific enhancer for Ephb4 shows enriched binding of SMAD1/5 and a requirement for SMAD binding motifs. Further, our results demonstrate that BMP/SMAD-mediated Ephb4 expression requires the venous-enriched BMP type I receptor ALK3/BMPR1A. Together, our analysis demonstrates a requirement for BMP signalling in the establishment of Ephb4 expression and the venous vasculature.
High-flux ultrafast extreme-ultraviolet photoemission spectroscopy at 18.4 MHz pulse repetition rate
Authors: Saule T. , Heinrich S. , Schötz J. , Lilienfein N. , Högner M. , deVries O. , Plötner M. , Weitenberg J. , Esser D. , Schulte J. , Russbueldt P. , Limpert J. , Kling M. F. , Kleineberg U. , Pupeza I. 
Published: January 2019

AbstractLaser-dressed photoelectron spectroscopy, employing extreme-ultraviolet attosecond pulses obtained by femtosecond-laser-driven high-order harmonic generation, grants access to atomic-scale electron dynamics. Limited by space charge effects determining the admissible number of photoelectrons ejected during each laser pulse, multidimensional (i.e. spatially or angle-resolved) attosecond photoelectron spectroscopy of solids and nanostructures requires high-photon-energy, broadband high harmonic sources operating at high repetition rates. Here, we present a high-conversion-efficiency, 18.4-MHz-repetition-rate cavity-enhanced high harmonic source emitting 5 × 105 photons per pulse in the 25-to-60-eV range, releasing 1 × 1010 photoelectrons per second from a 10-µm-diameter spot on tungsten, at space charge distortions of only a few tens of meV. Broadband, time-of-flight photoelectron detection with nearly 100% temporal duty cycle evidences a count rate improvement between two and three orders of magnitude over state-of-the-art attosecond photoelectron spectroscopy experiments under identical space charge conditions. The measurement time reduction and the photon energy scalability render this technology viable for next-generation, high-repetition-rate, multidimensional attosecond metrology.
A Rho-actin signaling pathway shapes cell wall boundaries in Arabidopsis xylem vessels
Authors: Sugiyama Yuki , Nagashima Yoshinobu , Wakazaki Mayumi , Sato Mayuko , Toyooka Kiminori , Fukuda Hiroo , Oda Yoshihisa 
Published: January 2019

AbstractPatterned cell wall deposition is crucial for cell shapes and functions. In Arabidopsis xylem vessels, ROP11 GTPase locally inhibits cell wall deposition through microtubule disassembly, inducing pits in cell walls. Here, we show that an additional ROP signaling pathway promotes cell wall growth at pit boundaries. Two proteins, Boundary of ROP domain1 (BDR1) and Wallin (WAL), localize to pit boundaries and regulate cell wall growth. WAL interacts with F-actin and promotes actin assembly at pit boundaries while BDR1 is a ROP effector. BDR1 interacts with WAL, suggesting that WAL could be recruited to the plasma membrane by a ROP-dependent mechanism. These results demonstrate that BDR1 and WAL mediate a ROP-actin pathway that shapes pit boundaries. The study reveals a distinct machinery in which two closely associated ROP pathways oppositely regulate cell wall deposition patterns for the establishment of tiny but highly specialized cell wall domains.
Forecasting dryland vegetation condition months in advance through satellite data assimilation
Authors: Tian Siyuan , Van Dijk Albert I. J. M. , Tregoning Paul , Renzullo Luigi J. 
Published: January 2019

AbstractDryland ecosystems are characterised by rainfall variability and strong vegetation response to changes in water availability over a range of timescales. Forecasting dryland vegetation condition can be of great value in planning agricultural decisions, drought relief, land management and fire preparedness. At monthly to seasonal time scales, knowledge of water stored in the system contributes more to predictability than knowledge of the climate system state. However, realising forecast skill requires knowledge of the vertical distribution of moisture below the surface and the capacity of the vegetation to access this moisture. Here, we demonstrate that contrasting satellite observations of water presence over different vertical domains can be assimilated into an eco-hydrological model and combined with vegetation observations to infer an apparent vegetation-accessible water storage (hereafter called accessible storage). Provided this variable is considered explicitly, skilful forecasts of vegetation condition are achievable several months in advance for most of the world’s drylands.
River channel connectivity shifts metabolite composition and dissolved organic matter chemistry
Authors: Lynch Laurel M. , Sutfin Nicholas A. , Fegel Timothy S. , Boot Claudia M. , Covino Timothy P. , Wallenstein Matthew D. 
Published: January 2019

AbstractBiogeochemical processing of dissolved organic matter (DOM) in headwater rivers regulates aquatic food web dynamics, water quality, and carbon storage. Although headwater rivers are critical sources of energy to downstream ecosystems, underlying mechanisms structuring DOM composition and reactivity are not well quantified. By pairing mass spectrometry and fluorescence spectroscopy, here we show that hydrology and river geomorphology interactively shape molecular patterns in DOM composition. River segments with a single channel flowing across the valley bottom export DOM with a similar chemical profile through time. In contrast, segments with multiple channels of flow store large volumes of water during peak flows, which they release downstream throughout the summer. As flows subside, losses of lateral floodplain connectivity significantly increase the heterogeneity of DOM exported downstream. By linking geomorphologic landscape-scale processes with microbial metabolism, we show DOM heterogeneity increases as a function of fluvial complexity, with implications for ecosystem function and watershed management.
Nuclear lipid droplets derive from a lipoprotein precursor and regulate phosphatidylcholine synthesis
Authors: Sołtysik Kamil , Ohsaki Yuki , Tatematsu Tsuyako , Cheng Jinglei , Fujimoto Toyoshi 
Published: January 2019

AbstractThe origin and physiological significance of lipid droplets (LDs) in the nucleus is not clear. Here we show that nuclear LDs in hepatocytes are derived from apolipoprotein B (ApoB)-free lumenal LDs, a precursor to very low-density lipoproprotein (VLDL) generated in the ER lumen by microsomal triglyceride transfer protein. ApoB-free lumenal LDs accumulate under ER stress, grow within the lumen of the type I nucleoplasmic reticulum, and turn into nucleoplasmic LDs by disintegration of the surrounding inner nuclear membrane. Oleic acid with or without tunicamycin significantly increases the formation of nucleoplasmic LDs, to which CTP:phosphocholine cytidylyltransferase α (CCTα) is recruited, resulting in activation of phosphatidylcholine (PC) synthesis. Perilipin-3 competes with CCTα in binding to nucleoplasmic LDs, and thus, knockdown and overexpression of perilipin-3 increases and decreases PC synthesis, respectively. The results indicate that nucleoplasmic LDs in hepatocytes constitute a feedback mechanism to regulate PC synthesis in accordance with ER stress.
Visible light-induced direct α C–H functionalization of alcohols
Authors: Niu Linbin , Liu Jiamei , Liang Xing-An , Wang Shengchun , Lei Aiwen 
Published: January 2019

AbstractConsidering the synthetic value of introducing active alcoholic hydroxyl group, developing C–H functionalization of alcohols is of significance. Herein, we present a photochemical method that under visible light irradiation, selectfluor can effectively promote the oxidative cross-coupling between alcohols and heteroarenes without the external photocatalysis, achieving the selective α sp3 C–H arylation of alcohol, even in the presence of ether. The N-F activation of selectfluor under blue LEDs irradiation is evidenced by electron paramagnetic resonance (EPR) study, which is the key process for the oxidative activation of α sp3 C–H alcohols. The observed reactivity may have significant implications for chemical transformations.
Genome structure and evolution of Antirrhinum majus L
Authors: Li Miaomiao , Zhang Dongfen , Gao Qiang , Luo Yingfeng , Zhang Hui , Ma Bin , Chen Chunhai , Whibley Annabel , Zhang Yu’e , Cao Yinghao , Li Qun , Guo Han , Li Junhui , Song Yanzhai , Zhang Yue , Copsey Lucy , Li Yan , Li Xiuxiu , Qi Ming , Wang Jiawei , Chen Yan , Wang Dan , Zhao Jinyang , Liu Guocheng , Wu Bin , Yu Lili , Xu Chunyan , Li Jiang , Zhao Shancen , Zhang Yijing , Hu Songnian , Liang Chengzhi , Yin Ye , Coen Enrico , Xue Yongbiao 
Published: January 2019

AbstractSnapdragon (Antirrhinum majus L.), a member of the Plantaginaceae family, is an important model for plant genetics and molecular studies on plant growth and development, transposon biology and self-incompatibility. Here we report a near-complete genome assembly of A. majus cultivar JI7 (A. majus cv.JI7) comprising 510 Megabases (Mb) of genomic sequence and containing 37,714 annotated protein-coding genes. Scaffolds covering 97.12% of the assembled genome were anchored on eight chromosomes. Comparative and evolutionary analyses revealed that a whole-genome duplication event occurred in the Plantaginaceae around 46–49 million years ago (Ma). We also uncovered the genetic architectures associated with complex traits such as flower asymmetry and self-incompatibility, identifying a unique duplication of TCP family genes dated to around 46–49 Ma and reconstructing a near-complete ψS-locus of roughly 2 Mb. The genome sequence obtained in this study not only provides a representative genome sequenced from the Plantaginaceae but also brings the popular plant model system of Antirrhinum into the genomic age.
Adiposity in relation to risks of fatty liver, cirrhosis and liver cancer: a prospective study of 0.5 million Chinese adults
Authors: Pang Yuanjie , Kartsonaki Christiana , Turnbull Iain , Guo Yu , Chen Yiping , Clarke Robert , Bian Zheng , Bragg Fiona , Millwood Iona Y. , Yang Ling , Huang Ying , Yang Yan , Zhang Xukui , Chen Junshi , Li Liming , Holmes Michael V. , Chen Zhengming 
Published: January 2019

AbstractAdiposity is an increasing public health problem in China. We aimed to examine the associations of adiposity with non-alcoholic fatty liver disease (NAFLD) and other chronic liver diseases in Chinese adults. The prospective China Kadoorie Biobank recruited 512,891 adults aged 30–79 years from 10 areas. During 10 years of follow-up, 7,386 incident liver disease cases were recorded among 503,991 participants without prior cancer or chronic liver disease at baseline. The mean body mass index (BMI) (SD) was 23.7 (3.3) kg/m2 and mean waist circumference (WC) 80.3 (9.8) cm, with 33% having BMI ≥25 kg/m2. Throughout the range examined (BMI 15–50) BMI showed a log-linear positive association with NAFLD (n = 1,298), with adjusted HR per 5 kg/m2 of 2.81 (95% CI 2.63–3.01), adjusting for regression dilution. There were also positive associations of percent body fat, WC, and waist-to-hip ratio with NAFLD, with HRs per 1-SD of 2.27 (2.14–2.41), 2.60 (2.44–2.76), and 1.84 (1.76–1.92). BMI was unrelated to viral hepatitis (n = 1,477), and had a U-shaped association with cirrhosis (n = 2,082) and an inverse association with liver cancer (n = 2,568), which disappeared after excluding the first 5 years of follow-up. Among Chinese adults, adiposity was a major risk factor for NAFLD but not other chronic liver diseases.
Genomic regions of speciation and adaptation among three species of grouse
Authors: Kozma Radoslav , Rödin-Mörch Patrik , Höglund Jacob 
Published: January 2019

AbstractUnderstanding the molecular basis of adaption is one of the central goals in evolutionary biology and when investigated across sister species it can provide detailed insight into the mechanisms of speciation. Here, we sequence the genomes of 34 individuals from three closely related grouse species in order to uncover the genomic architecture of speciation and the genes involved in adaptation. We identify 6 regions, containing 7 genes that show lineage specific signs of differential selection across the species. These genes are involved in a variety of cell processes ranging from stress response to neural, gut, olfactory and limb development. Genome wide neutrality test statistics reveal a strong signal of population expansion acting across the genomes. Additionally, we uncover a 3.5 Mb region on chromosome 20 that shows considerably lower levels of differentiation across the three grouse lineages, indicating possible action of uniform selection in this region.
Urotensin-related gene transcripts mark developmental emergence of the male forebrain vocal control system in songbirds
Authors: Bell Zachary W. , Lovell Peter , Mello Claudio V. , Yip Ping K. , George Julia M. , Clayton David F. 
Published: January 2019

AbstractSongbirds communicate through learned vocalizations, using a forebrain circuit with convergent similarity to vocal-control circuitry in humans. This circuit is incomplete in female zebra finches, hence only males sing. We show that the UTS2B gene, encoding Urotensin-Related Peptide (URP), is uniquely expressed in a key pre-motor vocal nucleus (HVC), and specifically marks the neurons that form a male-specific projection that encodes timing features of learned song. UTS2B-expressing cells appear early in males, prior to projection formation, but are not observed in the female nucleus. We find no expression evidence for canonical receptors within the vocal circuit, suggesting either signalling to other brain regions via diffusion or transduction through other receptor systems. Urotensins have not previously been implicated in vocal control, but we find an annotation in Allen Human Brain Atlas of increased UTS2B expression within portions of human inferior frontal cortex implicated in human speech and singing. Thus UTS2B (URP) is a novel neural marker that may have conserved functions for vocal communication.
DeepSeqPan, a novel deep convolutional neural network model for pan-specific class I HLA-peptide binding affinity prediction
Authors: Liu Zhonghao , Cui Yuxin , Xiong Zheng , Nasiri Alierza , Zhang Ansi , Hu Jianjun 
Published: January 2019

AbstractInteractions between human leukocyte antigens (HLAs) and peptides play a critical role in the human immune system. Accurate computational prediction of HLA-binding peptides can be used for peptide drug discovery. Currently, the best prediction algorithms are neural network-based pan-specific models, which take advantage of the large amount of data across HLA alleles. However, current pan-specific models are all based on the pseudo sequence encoding for modeling the binding context, which is based on 34 positions identified from the HLA protein-peptide bound structures in early works. In this work, we proposed a novel deep convolutional neural network model (DCNN) for HLA-peptide binding prediction, in which the encoding of the HLA sequence and the binding context are both learned by the network itself without requiring the HLA-peptide bound structure information. Our DCNN model is also characterized by its binding context extraction layer and dual outputs with both binding affinity output and binding probability outputs. Evaluation on public benchmark datasets shows that our DeepSeqPan model without HLA structural information in training achieves state-of-the-art performance on a large number of HLA alleles with good generalization capability. Since our model only needs raw sequences from the HLA-peptide binding pairs, it can be applied to binding predictions of HLAs without structure information and can also be applied to other protein binding problems such as protein-DNA and protein-RNA bindings. The implementation code and trained models are freely available at https://github.com/pcpLiu/DeepSeqPan.