bluuebunny/crossref_metadata_2025_split huggingface dataset:
POGLUT1, the putative effector gene driven by rs2293370 in primary biliary cholangitis susceptibility locus chromosome 3q13.33
Authors: Hitomi Yuki , Ueno Kazuko , Kawai Yosuke , Nishida Nao , Kojima Kaname , Kawashima Minae , Aiba Yoshihiro , Nakamura Hitomi , Kouno Hiroshi , Kouno Hirotaka , Ohta Hajime , Sugi Kazuhiro , Nikami Toshiki , Yamashita Tsutomu , Katsushima Shinji , Komeda Toshiki , Ario Keisuke , Naganuma Atsushi , Shimada Masaaki , Hirashima Noboru , Yoshizawa Kaname , Makita Fujio , Furuta Kiyoshi , Kikuchi Masahiro , Naeshiro Noriaki , Takahashi Hironao , Mano Yutaka , Yamashita Haruhiro , Matsushita Kouki , Tsunematsu Seiji , Yabuuchi Iwao , Nishimura Hideo , Shimada Yusuke , Yamauchi Kazuhiko , Komatsu Tatsuji , Sugimoto Rie , Sakai Hironori , Mita Eiji , Koda Masaharu , Nakamura Yoko , Kamitsukasa Hiroshi , Sato Takeaki , Nakamuta Makoto , Masaki Naohiko , Takikawa Hajime , Tanaka Atsushi , Ohira Hiromasa , Zeniya Mikio , Abe Masanori , Kaneko Shuichi , Honda Masao , Arai Kuniaki , Arinaga-Hino Teruko , Hashimoto Etsuko , Taniai Makiko , Umemura Takeji , Joshita Satoru , Nakao Kazuhiko , Ichikawa Tatsuki , Shibata Hidetaka , Takaki Akinobu , Yamagiwa Satoshi , Seike Masataka , Sakisaka Shotaro , Takeyama Yasuaki , Harada Masaru , Senju Michio , Yokosuka Osamu , Kanda Tatsuo , Ueno Yoshiyuki , Ebinuma Hirotoshi , Himoto Takashi , Murata Kazumoto , Shimoda Shinji , Nagaoka Shinya , Abiru Seigo , Komori Atsumasa , Migita Kiyoshi , Ito Masahiro , Yatsuhashi Hiroshi , Maehara Yoshihiko , Uemoto Shinji , Kokudo Norihiro , Nagasaki Masao , Tokunaga Katsushi , Nakamura Minoru 
Published: January 2019

AbstractPrimary biliary cholangitis (PBC) is a chronic and cholestatic autoimmune liver disease caused by the destruction of intrahepatic small bile ducts. Our previous genome-wide association study (GWAS) identified six susceptibility loci for PBC. Here, in order to further elucidate the genetic architecture of PBC, a GWAS was performed on an additional independent sample set, then a genome-wide meta-analysis with our previous GWAS was performed based on a whole-genome single nucleotide polymorphism (SNP) imputation analysis of a total of 4,045 Japanese individuals (2,060 cases and 1,985 healthy controls). A susceptibility locus on chromosome 3q13.33 (including ARHGAP31, TMEM39A, POGLUT1, TIMMDC1, and CD80) was previously identified both in the European and Chinese populations and was replicated in the Japanese population (OR = 0.7241, P = 3.5 × 10−9). Subsequent in silico and in vitro functional analyses identified rs2293370, previously reported as the top-hit SNP in this locus in the European population, as the primary functional SNP. Moreover, e-QTL analysis indicated that the effector gene of rs2293370 was Protein O-Glucosyltransferase 1 (POGLUT1) (P = 3.4 × 10−8). This is the first study to demonstrate that POGLUT1 and not CD80 is the effector gene regulated by the primary functional SNP rs2293370, and that increased expression of POGLUT1 might be involved in the pathogenesis of PBC.
Slow insertion of silicon probes improves the quality of acute neuronal recordings
Authors: Fiáth Richárd , Márton Adrienn Lilla , Mátyás Ferenc , Pinke Domonkos , Márton Gergely , Tóth Kinga , Ulbert István 
Published: January 2019

AbstractNeural probes designed for extracellular recording of brain electrical activity are traditionally implanted with an insertion speed between 1 µm/s and 1 mm/s into the brain tissue. Although the physical effects of insertion speed on the tissue are well studied, there is a lack of research investigating how the quality of the acquired electrophysiological signal depends on the speed of probe insertion. In this study, we used four different insertion speeds (0.002 mm/s, 0.02 mm/s, 0.1 mm/s, 1 mm/s) to implant high-density silicon probes into deep layers of the somatosensory cortex of ketamine/xylazine anesthetized rats. After implantation, various qualitative and quantitative properties of the recorded cortical activity were compared across different speeds in an acute manner. Our results demonstrate that after the slowest insertion both the signal-to-noise ratio and the number of separable single units were significantly higher compared with those measured after inserting probes at faster speeds. Furthermore, the amplitude of recorded spikes as well as the quality of single unit clusters showed similar speed-dependent differences. Post hoc quantification of the neuronal density around the probe track showed a significantly higher number of NeuN-labelled cells after the slowest insertion compared with the fastest insertion. Our findings suggest that advancing rigid probes slowly (~1 µm/s) into the brain tissue might result in less tissue damage, and thus in neuronal recordings of improved quality compared with measurements obtained after inserting probes with higher speeds.
Measuring Tumor Mutational Burden (TMB) in Plasma from mCRPC Patients Using Two Commercial NGS Assays
Authors: Qiu Ping , Poehlein Christian H. , Marton Matthew J. , Laterza Omar F. , Levitan Diane 
Published: January 2019

AbstractTumor tissue mutational burden (TMB) has emerged as a promising predictive biomarker for immune checkpoint therapy. Measuring TMB from circulating tumor DNA (ctDNA) found in plasma is attractive in tissue-constrained indications. We compared the performance of two plasma-based commercial TMB assays including the effect of two different collection methods. Our findings suggest that the two plasma based TMB assays are highly correlated and they are also both correlated with a tissue-based TMB assay for relatively high TMB samples. The two collection methods are also found to be very comparable. Plasma-based TMB assays may be mature enough to be clinically useful in mCRPC and potentially other indications.
A Nervous System-Specific Model of Creatine Transporter Deficiency Recapitulates the Cognitive Endophenotype of the Disease: a Longitudinal Study
Authors: Molinaro Angelo , Alessandrì Maria Grazia , Putignano Elena , Leuzzi Vincenzo , Cioni Giovanni , Baroncelli Laura , Pizzorusso Tommaso 
Published: January 2019

AbstractMutations in creatine (Cr) transporter (CrT) gene lead to cerebral creatine deficiency syndrome-1 (CTD), an orphan neurodevelopmental disorder presenting with brain Cr deficiency, intellectual disability, seizures, movement and autistic-like behavioral disturbances, language and speech impairment. We have recently generated a murine model of CTD obtained by ubiquitous deletion of 5–7 exons in the CrT gene. These mice showed a marked Cr depletion, associated to early and progressive cognitive impairment, and autistic-like defects, thus resembling the key features of human CTD. Given the importance of extraneural dysfunctions in neurodevelopmental disorders, here we analyzed the specific role of neural Cr in the CTD phenotype. We induced the conditional deletion of Slc6a8 gene in neuronal and glial cells by crossing CrT floxed mice with the Nestin::Cre recombinase Tg (Nes-cre) 1Kln mouse. We report that nervous system-specific Cr depletion leads to a progressive cognitive regression starting in the adult age. No autistic-like features, including repetitive and stereotyped movements, routines and rituals, are present in this model. These results indicate that Cr depletion in the nervous system is a pivotal cause of the CTD pathological phenotype, in particular with regard to the cognitive domain, but extraneural actors also play a role.
The downed and dead wood inventory of forests in the United States
Authors: Woodall Christopher W. , Monleon Vicente J. , Fraver Shawn , Russell Matthew B. , Hatfield Mark H. , Campbell John L. , Domke Grant M. 
Published: January 2019

AbstractThe quantity and condition of downed dead wood (DDW) is emerging as a major factor governing forest ecosystem processes such as carbon cycling, fire behavior, and tree regeneration. Despite this, systematic inventories of DDW are sparse if not absent across major forest biomes. The Forest Inventory and Analysis program of the United States (US) Forest Service has conducted an annual DDW inventory on all coterminous US forest land since 2002 (~1 plot per 38,850 ha), with a sample intensification occurring since 2012 (~1 plot per 19,425 ha). The data are organized according to DDW components and by sampling information which can all be linked to a multitude of auxiliary information in the national database. As the sampling of DDW is conducted using field efficient line-intersect approaches, several assumptions are adopted during population estimation that serve to identify critical knowledge gaps. The plot- and population-level DDW datasets and estimates provide the first insights into an understudied but critical ecosystem component of temperate forests of North America with global application.
Identification of substrate-specific inhibitors of cathepsin K through high-throughput screening
Authors: Law Simon , Du Xin , Panwar Preety , Honson Nicolette S. , Pfeifer Tom , Roberge Michel , Brömme Dieter 
Published: January 2019

Abstract
Cathepsin K (CatK) is a cysteine protease and drug target for skeletal disorders that is known for its potent collagenase and elastase activity. The formation of oligomeric complexes of CatK in the presence of glycosaminoglycans has been associated with its collagenase activity. Inhibitors that disrupt these complexes can selectively block the collagenase activity without interfering with the other regulatory proteolytic activities of the enzyme. Here, we have developed a fluorescence polarization (FP) assay to screen 4761 compounds for substrate-specific ectosteric collagenase inhibitors of CatK. A total of 38 compounds were identified that block the collagenase activity without interfering with the hydrolysis of active site substrates such as the synthetic peptide substrate, benzyloxycarbonyl-Phe-Arg-7-amido-4-methylcoumarin, and gelatin. The identified inhibitors can be divided into two main classes, negatively charged and polyaromatic compounds which suggest the binding to different ectosteric sites. Two of the inhibitors were highly effective in preventing the bone-resorption activity of CatK in osteoclasts. Interestingly, some of the ectosteric inhibitors were capable of differentiating between the collagenase and elastase activity of CatK depending on the ectosteric site utilized by the compound. Owing to their substrate-specific selectivity, ectosteric inhibitors represent a viable alternative to side effect-prone active site-directed inhibitors.
Fetal programming and the angiotensin-(1-7) axis: a review of the experimental and clinical data
Authors: South Andrew M. , Shaltout Hossam A. , Washburn Lisa K. , Hendricks Alexa S. , Diz Debra I. , Chappell Mark C. 
Published: January 2019

AbstractHypertension is the primary risk factor for cardiovascular disease that constitutes a serious worldwide health concern and a significant healthcare burden. As the majority of hypertension has an unknown etiology, considerable research efforts in both experimental models and human cohorts has focused on the premise that alterations in the fetal and perinatal environment are key factors in the development of hypertension in children and adults. The exact mechanisms of how fetal programming events increase the risk of hypertension and cardiovascular disease are not fully elaborated; however, the focus on alterations in the biochemical components and functional aspects of the renin–angiotensin (Ang) system (RAS) has predominated, particularly activation of the Ang-converting enzyme (ACE)-Ang II-Ang type 1 receptor (AT1R) axis. The emerging view of alternative pathways within the RAS that may functionally antagonize the Ang II axis raise the possibility that programming events also target the non-classical components of the RAS as an additional mechanism contributing to the development and progression of hypertension. In the current review, we evaluate the potential role of the ACE2-Ang-(1-7)-Mas receptor (MasR) axis of the RAS in fetal programming events and cardiovascular and renal dysfunction. Specifically, the review examines the impact of fetal programming on the Ang-(1-7) axis within the circulation, kidney, and brain such that the loss of Ang-(1-7) expression or tone, contributes to the chronic dysregulation of blood pressure (BP) and cardiometabolic disease in the offspring, as well as the influence of sex on potential programming of this pathway.
USP4 deficiency exacerbates hepatic ischaemia/reperfusion injury via TAK1 signalling
Authors: Zhou Jiangqiao , Qiu Tao , Wang Tianyu , Chen Zhongbao , Ma Xiaoxiong , Zhang Long , Zou Jilin 
Published: January 2019

Abstract
Ubiquitin-specific peptidase 4 (USP4) protein is a type of deubiquitination enzyme that is correlated with many important biological processes. However, the function of USP4 in hepatic ischaemia/reperfusion (I/R) injury remains unknown. The aim of the present study was to explore the role of USP4 in hepatic I/R injury. USP4 gene knockout mice and primary hepatocytes were used to construct hepatic I/R models. The effect of USP4 on hepatic I/R injury was examined via pathological and molecular analyses. Our results indicated that USP4 was significantly up-regulated in liver of mice subjected to hepatic I/R injury. USP4 knockout mice exhibited exacerbated hepatic I/R injury, as evidenced by enhanced liver inflammation via the nuclear factor κB (NF-κB) signalling pathway and increased hepatocyte apoptosis. Additionally, USP4 overexpression inhibited hepatocyte inflammation and apoptosis on hepatic I/R stimulation. Mechanistically, our study demonstrates that USP4 deficiency exerts its detrimental effects on hepatic I/R injury by inducing activation of the transforming growth factor β-activated kinase 1 (TAK1)/JNK signalling pathways. TAK1 was required for USP4 function in hepatic I/R injury as TAK1 inhibition abolished USP4 function in vitro. In conclusion, our study demonstrates that USP4 deficiency plays a detrimental role in hepatic I/R injury by promoting activation of the TAK1/JNK signalling pathways. Modulation of this axis may be a novel strategy to alleviate the pathological process of hepatic I/R injury.
Optical spectroscopic and polarization properties of 2011 outburst of the recurrent nova T Pyxidis
Authors: Pavana M. , Anche Ramya M. , Anupama G. C. , Ramaprakash A. N. , Selvakumar G. 
Published: January 2019

Aims. We aim to study the spectroscopic and ionized structural evolution of T Pyx during its 2011 outburst, and also study the variation in degree of polarization during its early phase.
Methods. Optical spectroscopic data of this system obtained from day 1.28–2415.62 since discovery, and optical, broadband imaging polarimetric observations obtained from day 1.36–29.33 during the early phases of the outburst were used in the study. The physical conditions and the geometry of the ionized structure of the nova ejecta was modelled for a few epochs using the photo-ionization code, CLOUDY in 1D and pyCloudy in 3D.
Results. The spectral evolution of the nova ejecta during its 2011 outburst is similar to that of the previous outbursts. The variation in the line profiles is seen very clearly in the early stages due to good coverage during this period. The line profiles vary from P Cygni (narrower, deeper, and sharper) to emission profiles that are broader and structured, which later become narrower and sharper in the late post-outburst phase. The average ejected mass is estimated to be 7.03 × 10−6 M⊙. The ionized structure of the ejecta is found to be a bipolar conical structure with equatorial rings, with a low inclination angle of 14.75 ° ±0.65°.
Shape evolution of cometary nuclei via anisotropic mass loss
Authors: Vavilov D. E. , Eggl S. , Medvedev Yu. D. , Zatitskiy P. B. 
Published: January 2019

Context.Breathtaking imagery recorded during the European Space Agency Rosetta mission confirmed the bilobate nature of the nucleus of comet 67P/Churyumov-Gerasimenko. The peculiar appearance of the nucleus is not unique among comets. The majority of cometary cores imaged at high resolution exhibit a similar build. Various theories have been brought forward as to how cometary nuclei attain such peculiar shapes.Aims.We illustrate that anisotropic mass loss and local collapse of subsurface structures caused by non-uniform exposure of the nucleus to solar irradiation can transform initially spherical comet cores into bilobed cores.Methods.We derived a mathematical framework to describe the changes in morphology resulting from non-uniform insolation during the spin-orbit evolution of a nucleus. We solved the resulting partial differential equations that govern the change in the shape of a nucleus subject to mass loss and consequent collapse of depleted subsurface structures analytically for simple insolation configurations and numerically for more realistic scenarios.Results.The proposed mechanism is capable of explaining why a large percentage of periodic comets appear to have peanut-shaped cores and why light-curve amplitudes of comet nuclei are on average larger than those of typical main belt asteroids of the same size.
An electrodynamic energy harvester with a 3D printed magnet and optimized topology
Authors: Wang Zhongxu , Huber Christian , Hu Jun , He Jinliang , Suess Dieter , Wang Shan X. 
Published: January 2019

Abstract
An electrodynamic energy harvester is proposed for scavenging the electromagnetic energy in the vicinity of a power transmission line. To improve the efficiency and to maximize the distortion power factor of the energy harvester, the permanent magnet in the energy harvester is especially designed by the finite element method to optimize the topology and subsequently fabricated by additive manufacturing. An isotropic polymer-bonded NdFeB material is used for the fused-deposition modeling 3D printing process. Tensile tests of the printed magnetic parts show proper mechanical properties for harsh environments. Compared to a non-optimized magnet, the distortion power factor can be increased by 55%. The power and power density under the resonance condition of the fabricated harvester can reach 93 mW and 2.6 mW/cm3, respectively. The advantages of such an optimized energy harvester include being a fast and affordable manufacturing technique, an enhanced distortion power factor, and high output power. The properties of the energy harvester show that it has great potential for many self-powered applications such as wireless sensor networks and Internet of things.
The bright side of PV production in snow-covered mountains
Authors: Kahl Annelen , Dujardin Jérôme , Lehning Michael 
Published: January 2019

Significance
Our work shows that it is possible to turn solar photovoltaics (PV) into a more reliable and better-suited contributor to a future renewable energy mix. The correct placement and orientation of solar panels in mountain areas shift a significant amount of electricity generation from the summer to the winter months. PV technology is economically and technologically very promising. Bringing the production pattern closer to typical consumption patterns in the midlatitudes represents an important step toward higher penetration of PV technology on future energy markets. Moreover, a reduction of the winter energy gap by placing PV on (existing) mountain infrastructure lowers the need for (unrealistic) additional storage.
Clonal-level lineage commitment pathways of hematopoietic stem cells in vivo
Authors: Lu Rong , Czechowicz Agnieszka , Seita Jun , Jiang Du , Weissman Irving L. 
Published: January 2019

Significance
Hematopoietic stem cells (HSCs) are the key therapeutic component of bone marrow transplantation, the first and most prevalent clinical stem cell therapy. HSCs sustain daily and life-long blood and immune production through a complex stepwise lineage commitment process. In this work, we analyzed HSC lineage commitment at the clonal level and identified HSC regulatory mechanisms that are undetectable by conventional population-level studies. We uncovered distinct HSC clonal pathways that lead to differential blood production and imbalances. Furthermore, we showed that regulation of HSCs transplanted into unconditioned hosts is strikingly different from that after irradiation and after an antagonistic antibody treatment, which has important implications for understanding, interpreting, and optimizing HSC transplantation.
The methyltransferase SETD6 regulates Mitotic progression through PLK1 methylation
Authors: Feldman Michal , Vershinin Zlata , Goliand Inna , Elia Natalie , Levy Dan 
Published: January 2019

Significance
The involvement of nonhistone protein methylation in cellular essential pathways is a rising field. Here we show evidence for the involvement of direct lysine methylation of the mitosis regulator PLK1 by SETD6 methyltransferase in cell cycle promotion. Our results reveal that this methylation occurs on two lysine residues and that lack of methylation leads to enhanced PLK1 catalytic activity, causing accelerated mitosis pace and thus faster proliferation rates. These findings suggest that PLK1 methylation by SETD6 controls the pace of mitotic progression, greatly enhancing our understanding of cell cycle complexity. The role of methylation in mitotic progression raises the possibility of its involvement in tumorigenic pathways by orchestrating cell division rates and might have insightful implications for the development of cancer-specific markers.
Direct observation of crystallization and melting with colloids
Authors: Hwang Hyerim , Weitz David A. , Spaepen Frans 
Published: January 2019

Significance
This paper reports on colloid experiments that provide a unique 3D experimental view at the particle level of the fundamental mechanism by which liquids crystallize and crystals melt. Since these mechanisms cannot be observed directly in atomic systems, the colloids serve as models to identify, for example, the equivalent of the often-invoked collision-limited growth of pure crystals. Other observations include the measurement of equal mobilities for growth and melting and the mobility of the body-centered cubic interface being greater than that of the face-centered cubic one.
Chemically induced vesiculation as a platform for studying TMEM16F activity
Authors: Han Tina W. , Ye Wenlei , Bethel Neville P. , Zubia Mario , Kim Andrew , Li Kathy H. , Burlingame Alma L. , Grabe Michael , Jan Yuh Nung , Jan Lily Y. 
Published: January 2019

Significance
Extracellular vesicles, which are released from cells via budding of the cell membrane and may carry bioactive cargo such as RNAs and proteins, can elicit biological activity in other cells in a short-range or long-range manner. Extracellular vesicles that depend on TMEM16F activity for their formation play important roles in blood coagulation, mineral deposition during bone development, and protection of the joint in inflammatory arthritis. This study employs a newly developed kinetic assay to investigate the TMEM16F protein functions that are involved in extracellular vesicle formation, such as TMEM16F-dependent calcium influx and TMEM16F-dependent phospholipid scrambling.