bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying therapeutic targets by combining transcriptional data with ordinal clinical measurements
Authors: Pirhaji Leila , Milani Pamela , Dalin Simona , Wassie Brook T. , Dunn Denise E. , Fenster Robert J. , Avila-Pacheco Julian , Greengard Paul , Clish Clary B. , Heiman Myriam , Lo Donald C. , Fraenkel Ernest 
Published: September 2017

AbstractThe immense and growing repositories of transcriptional data may contain critical insights for developing new therapies. Current approaches to mining these data largely rely on binary classifications of disease vs. control, and are not able to incorporate measures of disease severity. We report an analytical approach to integrate ordinal clinical information with transcriptomics. We apply this method to public data for a large cohort of Huntington’s disease patients and controls, identifying and prioritizing phenotype-associated genes. We verify the role of a high-ranked gene in dysregulation of sphingolipid metabolism in the disease and demonstrate that inhibiting the enzyme, sphingosine-1-phosphate lyase 1 (SPL), has neuroprotective effects in Huntington’s disease models. Finally, we show that one consequence of inhibiting SPL is intracellular inhibition of histone deacetylases, thus linking our observations in sphingolipid metabolism to a well-characterized Huntington’s disease pathway. Our approach is easily applied to any data with ordinal clinical measurements, and may deepen our understanding of disease processes.
Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis
Authors: Benyamin Beben , He Ji , Zhao Qiongyi , Gratten Jacob , Garton Fleur , Leo Paul J. , Liu Zhijun , Mangelsdorf Marie , Al-Chalabi Ammar , Anderson Lisa , Butler Timothy J. , Chen Lu , Chen Xiang-Ding , Cremin Katie , Deng Hong-Weng , Devine Matthew , Edson Janette , Fifita Jennifer A. , Furlong Sarah , Han Ying-Ying , Harris Jessica , Henders Anjali K. , Jeffree Rosalind L. , Jin Zi-Bing , Li Zhongshan , Li Ting , Li Mengmeng , Lin Yong , Liu Xiaolu , Marshall Mhairi , McCann Emily P. , Mowry Bryan J. , Ngo Shyuan T. , Pamphlett Roger , Ran Shu , Reutens David C. , Rowe Dominic B. , Sachdev Perminder , Shah Sonia , Song Sharon , Tan Li-Jun , Tang Lu , van den Berg Leonard H. , van Rheenen Wouter , Veldink Jan H. , Wallace Robyn H. , Wheeler Lawrie , Williams Kelly L. , Wu Jinyu , Wu Xin , Yang Jian , Yue Weihua , Zhang Zong-Hong , Zhang Dai , Noakes Peter G. , Blair Ian P. , Henderson Robert D. , McCombe Pamela A. , Visscher Peter M. , Xu Huji , Bartlett Perry F. , Brown Matthew A. , Wray Naomi R. , Fan Dongsheng 
Published: September 2017

AbstractCross-ethnic genetic studies can leverage power from differences in disease epidemiology and population-specific genetic architecture. In particular, the differences in linkage disequilibrium and allele frequency patterns across ethnic groups may increase gene-mapping resolution. Here we use cross-ethnic genetic data in sporadic amyotrophic lateral sclerosis (ALS), an adult-onset, rapidly progressing neurodegenerative disease. We report analyses of novel genome-wide association study data of 1,234 ALS cases and 2,850 controls. We find a significant association of rs10463311 spanning GPX3-TNIP1 with ALS (p = 1.3 × 10−8), with replication support from two independent Australian samples (combined 576 cases and 683 controls, p = 1.7 × 10−3). Both GPX3 and TNIP1 interact with other known ALS genes (SOD1 and OPTN, respectively). In addition, GGNBP2 was identified using gene-based analysis and summary statistics-based Mendelian randomization analysis, although further replication is needed to confirm this result. Our results increase our understanding of genetic aetiology of ALS.
Strain-engineered growth of two-dimensional materials
Authors: Ahn Geun Ho , Amani Matin , Rasool Haider , Lien Der-Hsien , Mastandrea James P. , Ager III Joel W. , Dubey Madan , Chrzan Daryl C. , Minor Andrew M. , Javey Ali 
Published: September 2017

AbstractThe application of strain to semiconductors allows for controlled modification of their band structure. This principle is employed for the manufacturing of devices ranging from high-performance transistors to solid-state lasers. Traditionally, strain is typically achieved via growth on lattice-mismatched substrates. For two-dimensional (2D) semiconductors, this is not feasible as they typically do not interact epitaxially with the substrate. Here, we demonstrate controlled strain engineering of 2D semiconductors during synthesis by utilizing the thermal coefficient of expansion mismatch between the substrate and semiconductor. Using WSe2 as a model system, we demonstrate stable built-in strains ranging from 1% tensile to 0.2% compressive on substrates with different thermal coefficient of expansion. Consequently, we observe a dramatic modulation of the band structure, manifested by a strain-driven indirect-to-direct bandgap transition and brightening of the dark exciton in bilayer and monolayer WSe2, respectively. The growth method developed here should enable flexibility in design of more sophisticated devices based on 2D materials.
The non-canonical poly(A) polymerase FAM46C acts as an onco-suppressor in multiple myeloma
Authors: Mroczek Seweryn , Chlebowska Justyna , Kuliński Tomasz M. , Gewartowska Olga , Gruchota Jakub , Cysewski Dominik , Liudkovska Vladyslava , Borsuk Ewa , Nowis Dominika , Dziembowski Andrzej 
Published: September 2017

AbstractFAM46C is one of the most frequently mutated genes in multiple myeloma. Here, using a combination of in vitro and in vivo approaches, we demonstrate that FAM46C encodes an active non-canonical poly(A) polymerase which enhances mRNA stability and gene expression. Reintroduction of active FAM46C into multiple myeloma cell lines, but not its catalytically-inactive mutant, leads to broad polyadenylation and stabilization of mRNAs strongly enriched with those encoding endoplasmic reticulum-targeted proteins and induces cell death. Moreover, silencing of FAM46C in multiple myeloma cells expressing WT protein enhance cell proliferation. Finally, using a FAM46C-FLAG knock-in mouse strain, we show that the FAM46C protein is strongly induced during activation of primary splenocytes and that B lymphocytes isolated from newly generated FAM46C KO mice proliferate faster than those isolated from their WT littermates. Concluding, our data clearly indicate that FAM46C works as an onco-suppressor, with the specificity for B-lymphocyte lineage from which multiple myeloma originates.
Late Neoproterozoic seawater oxygenation by siliceous sponges
Authors: Tatzel Michael , von Blanckenburg Friedhelm , Oelze Marcus , Bouchez Julien , Hippler Dorothee 
Published: September 2017

AbstractThe Cambrian explosion, the rapid appearance of most animal phyla in the geological record, occurred concurrently with bottom seawater oxygenation. Whether this oxygenation event was triggered through enhanced nutrient supply and organic carbon burial forced by increased continental weathering, or by species engaging in ecosystem engineering, remains a fundamental yet unresolved question. Here we provide evidence for several simultaneous developments that took place over the Ediacaran–Cambrian transition: expansion of siliceous sponges, decrease of the dissolved organic carbon pool, enhanced organic carbon burial, increased phosphorus removal and seawater oxygenation. This evidence is based on silicon and carbon stable isotopes, Ge/Si ratios, REE-geochemistry and redox-sensitive elements in a chert-shale succession from the Yangtze Platform, China. According to this reconstruction, sponges have initiated seawater oxygenation by redistributing organic carbon oxidation through filtering suspended organic matter from seawater. The resulting increase in dissolved oxygen levels potentially triggered the diversification of eumetazoans.
Distal axotomy enhances retrograde presynaptic excitability onto injured pyramidal neurons via trans-synaptic signaling
Authors: Nagendran Tharkika , Larsen Rylan S. , Bigler Rebecca L. , Frost Shawn B. , Philpot Benjamin D. , Nudo Randolph J. , Taylor Anne Marion 
Published: September 2017

AbstractInjury of CNS nerve tracts remodels circuitry through dendritic spine loss and hyper-excitability, thus influencing recovery. Due to the complexity of the CNS, a mechanistic understanding of injury-induced synaptic remodeling remains unclear. Using microfluidic chambers to separate and injure distal axons, we show that axotomy causes retrograde dendritic spine loss at directly injured pyramidal neurons followed by retrograde presynaptic hyper-excitability. These remodeling events require activity at the site of injury, axon-to-soma signaling, and transcription. Similarly, directly injured corticospinal neurons in vivo also exhibit a specific increase in spiking following axon injury. Axotomy-induced hyper-excitability of cultured neurons coincides with elimination of inhibitory inputs onto injured neurons, including those formed onto dendritic spines. Netrin-1 downregulation occurs following axon injury and exogenous netrin-1 applied after injury normalizes spine density, presynaptic excitability, and inhibitory inputs at injured neurons. Our findings show that intrinsic signaling within damaged neurons regulates synaptic remodeling and involves netrin-1 signaling.
Optical trapping of otoliths drives vestibular behaviours in larval zebrafish
Authors: Favre-Bulle Itia A. , Stilgoe Alexander B. , Rubinsztein-Dunlop Halina , Scott Ethan K. 
Published: September 2017

AbstractThe vestibular system, which detects gravity and motion, is crucial to survival, but the neural circuits processing vestibular information remain incompletely characterised. In part, this is because the movement needed to stimulate the vestibular system hampers traditional neuroscientific methods. Optical trapping uses focussed light to apply forces to targeted objects, typically ranging from nanometres to a few microns across. In principle, optical trapping of the otoliths (ear stones) could produce fictive vestibular stimuli in a stationary animal. Here we use optical trapping in vivo to manipulate 55-micron otoliths in larval zebrafish. Medial and lateral forces on the otoliths result in complementary corrective tail movements, and lateral forces on either otolith are sufficient to cause a rolling correction in both eyes. This confirms that optical trapping is sufficiently powerful and precise to move large objects in vivo, and sets the stage for the functional mapping of the resulting vestibular processing.
Laminar differences in decision-related neural activity in dorsal premotor cortex
Authors: Chandrasekaran Chandramouli , Peixoto Diogo , Newsome William T. , Shenoy Krishna V. 
Published: September 2017

AbstractDorsal premotor cortex is implicated in somatomotor decisions. However, we do not understand the temporal patterns and laminar organization of decision-related firing rates in dorsal premotor cortex. We recorded neurons from dorsal premotor cortex of monkeys performing a visual discrimination task with reaches as the behavioral report. We show that these neurons can be organized along a bidirectional visuomotor continuum based on task-related firing rates. “Increased” neurons at one end of the continuum increased their firing rates ~150 ms after stimulus onset and these firing rates covaried systematically with choice, stimulus difficulty, and reaction time—characteristics of a candidate decision variable. “Decreased” neurons at the other end of the continuum reduced their firing rate after stimulus onset, while “perimovement” neurons at the center of the continuum responded only ~150 ms before movement initiation. These neurons did not show decision variable-like characteristics. “Increased” neurons were more prevalent in superficial layers of dorsal premotor cortex; deeper layers contained more “decreased” and “perimovement” neurons. These results suggest a laminar organization for decision-related responses in dorsal premotor cortex.
Peer punishment promotes enforcement of bad social norms
Authors: Abbink Klaus , Gangadharan Lata , Handfield Toby , Thrasher John 
Published: September 2017

AbstractSocial norms are an important element in explaining how humans achieve very high levels of cooperative activity. It is widely observed that, when norms can be enforced by peer punishment, groups are able to resolve social dilemmas in prosocial, cooperative ways. Here we show that punishment can also encourage participation in destructive behaviours that are harmful to group welfare, and that this phenomenon is mediated by a social norm. In a variation of a public goods game, in which the return to investment is negative for both group and individual, we find that the opportunity to punish led to higher levels of contribution, thereby harming collective payoffs. A second experiment confirmed that, independently of whether punishment is available, a majority of subjects regard the efficient behaviour of non-contribution as socially inappropriate. The results show that simply providing a punishment opportunity does not guarantee that punishment will be used for socially beneficial ends, because the social norms that influence punishment behaviour may themselves be destructive.
Silicon single-photon avalanche diodes with nano-structured light trapping
Authors: Zang Kai , Jiang Xiao , Huo Yijie , Ding Xun , Morea Matthew , Chen Xiaochi , Lu Ching-Ying , Ma Jian , Zhou Ming , Xia Zhenyang , Yu Zongfu , Kamins Theodore I. , Zhang Qiang , Harris James S. 
Published: September 2017

AbstractSilicon single-photon avalanche detectors are becoming increasingly significant in research and in practical applications due to their high signal-to-noise ratio, complementary metal oxide semiconductor compatibility, room temperature operation, and cost-effectiveness. However, there is a trade-off in current silicon single-photon avalanche detectors, especially in the near infrared regime. Thick-junction devices have decent photon detection efficiency but poor timing jitter, while thin-junction devices have good timing jitter but poor efficiency. Here, we demonstrate a light-trapping, thin-junction Si single-photon avalanche diode that breaks this trade-off, by diffracting the incident photons into the horizontal waveguide mode, thus significantly increasing the absorption length. The photon detection efficiency has a 2.5-fold improvement in the near infrared regime, while the timing jitter remains 25 ps. The result provides a practical and complementary metal oxide semiconductor compatible method to improve the performance of single-photon avalanche detectors, image sensor arrays, and silicon photomultipliers over a broad spectral range.
Disrupted topological organization of structural brain networks in childhood absence epilepsy
Authors: Qiu Wenchao , Yu Chuanyong , Gao Yuan , Miao Ailiang , Tang Lu , Huang Shuyang , Jiang Wenwen , Sun Jintao , Xiang Jing , Wang Xiaoshan 
Published: September 2017

AbstractChildhood absence epilepsy (CAE) is the most common paediatric epilepsy syndrome and is characterized by frequent and transient impairment of consciousness. In this study, we explored structural brain network alterations in CAE and their association with clinical characteristics. A whole-brain structural network was constructed for each participant based on diffusion-weighted MRI and probabilistic tractography. The topological metrics were then evaluated. For the first time, we uncovered modular topology in CAE patients that was similar to healthy controls. However, the strength, efficiency and small-world properties of the structural network in CAE were seriously damaged. At the whole brain level, decreased strength, global efficiency, local efficiency, clustering coefficient, normalized clustering coefficient and small-worldness values of the network were detected in CAE, while the values of characteristic path length and normalized characteristic path length were abnormally increased. At the regional level, especially the prominent regions of the bilateral precuneus showed reduced nodal efficiency, and the reduction of efficiency was significantly correlated with disease duration. The current results demonstrate significant alterations of structural networks in CAE patients, and the impairments tend to grow worse over time. Our findings may provide a new way to understand the pathophysiological mechanism of CAE.
Multiwell capillarity-based microfluidic device for the study of 3D tumour tissue-2D endothelium interactions and drug screening in co-culture models
Authors: Virumbrales-Muñoz María , Ayuso José María , Olave Marta , Monge Rosa , de Miguel Diego , Martínez-Lostao Luis , Le Gac Séverine , Doblare Manuel , Ochoa Ignacio , Fernandez Luis J. 
Published: September 2017

AbstractThe tumour microenvironment is very complex, and essential in tumour development and drug resistance. The endothelium is critical in the tumour microenvironment: it provides nutrients and oxygen to the tumour and is essential for systemic drug delivery. Therefore, we report a simple, user-friendly microfluidic device for co-culture of a 3D breast tumour model and a 2D endothelium model for cross-talk and drug delivery studies. First, we demonstrated the endothelium was functional, whereas the tumour model exhibitedin vivofeatures,e.g., oxygen gradients and preferential proliferation of cells with better access to nutrients and oxygen. Next, we observed the endothelium structure lost its integrity in the co-culture. Following this, we evaluated two drug formulations of TRAIL (TNF-related apoptosis inducing ligand): soluble and anchored to a LUV (large unilamellar vesicle). Both diffused through the endothelium, LUV-TRAIL being more efficient in killing tumour cells, showing no effect on the integrity of endothelium. Overall, we have developed a simple capillary force-based microfluidic device for 2D and 3D cell co-cultures. Our device allows high-throughput approaches, patterning different cell types and generating gradients without specialised equipment. We anticipate this microfluidic device will facilitate drug screening in a relevant microenvironment thanks to its simple, effective and user-friendly operation.
Discrete-Time Quantum Walk with Phase Disorder: Localization and Entanglement Entropy
Authors: Zeng Meng , Yong Ee Hou 
Published: September 2017

AbstractQuantum Walk (QW) has very different transport properties to its classical counterpart due to interference effects. Here we study the discrete-time quantum walk (DTQW) with on-site static/dynamic phase disorder following either binary or uniform distribution in both one and two dimensions. For one dimension, we consider the Hadamard coin; for two dimensions, we consider either a 2-level Hadamard coin (Hadamard walk) or a 4-level Grover coin (Grover walk) for the rotation in coin-space. We study the transport properties e.g. inverse participation ratio (IPR) and the standard deviation of the density function (σ) as well as the coin-position entanglement entropy (EE), due to the two types of phase disorders and the two types of coins. Our numerical simulations show that the dimensionality, the type of coins, and whether the disorder is static or dynamic play a pivotal role and lead to interesting behaviors of the DTQW. The distribution of the phase disorder has very minor effects on the quantum walk.
Loss of p73 in ependymal cells during the perinatal period leads to aqueductal stenosis
Authors: Fujitani Masashi , Sato Ryohei , Yamashita Toshihide 
Published: September 2017

AbstractThe p53 family member p73 plays a critical role in brain development. p73 knockout mice exhibit a number of deficits in the nervous system, such as neuronal death, hydrocephalus, hippocampal dysgenesis, and pheromonal defects. Among these phenotypes, the mechanisms of hydrocephalus remain unknown. In this study, we generated a p73 knock-in (KI) mutant mouse and a conditional p73 knockout mouse. The homozygous KI mutants showed aqueductal stenosis. p73 was expressed in the ependymal cell layer and several brain areas. Unexpectedly, when p73 was disrupted during the postnatal period, animals showed aqueductal stenosis at a later stage but not hydrocephalus. An assessment of the integrity of cilia and basal body (BB) patch formation suggests that p73 is required to establish translational polarity but not to establish rotational polarity or the planar polarization of BB patches. Deletion of p73 in adult ependymal cells did not affect the maintenance of translational polarity. These results suggest that the loss of p73 during the embryonic period is critical for hydrocephalus development.
Characterization of Methane Excess and Absolute Adsorption in Various Clay Nanopores from Molecular Simulation
Authors: Tian Yuanyuan , Yan Changhui , Jin Zhehui 
Published: September 2017

AbstractIn this work, we use grand canonical Monte Carlo (GCMC) simulation to study methane adsorption in various clay nanopores and analyze different approaches to characterize the absolute adsorption. As an important constituent of shale, clay minerals can have significant amount of nanopores, which greatly contribute to the gas-in-place in shale. In previous works, absolute adsorption is often calculated from the excess adsorption and bulk liquid phase density of absorbate. We find that methane adsorbed phase density keeps increasing with pressure up to 80 MPa. Even with updated adsorbed phase density from GCMC, there is a significant error in absolute adsorption calculation. Thus, we propose to use the excess adsorption and adsorbed phase volume to calculate absolute adsorption and reduce the discrepancy to less than 3% at high pressure conditions. We also find that the supercritical Dubinin-Radushkevich (SDR) fitting method which is commonly used in experiments to convert the excess adsorption to absolute adsorption may not have a solid physical foundation for methane adsorption. The methane excess and absolute adsorptions per specific surface area are similar for different clay minerals in line with previous experimental data. In mesopores, the excess and absolute adsorptions per specific surface area become insensitive to pore size. Our work should provide important fundamental understandings and insights into accurate estimation of gas-in-place in shale reservoirs.
Use of medroxyprogesterone acetate in women with ovarian endometriosis undergoing controlled ovarian hyperstimulation for in vitro fertilization
Authors: Guo Haiyan , Wang Yun , Chen Qiuju , Chai Weiran , Sun Lihua , Ai Ai , Fu Yonglun , Lyu Qifeng , Kuang Yanping 
Published: September 2017

AbstractThis study investigated the use of medroxyprogesterone acetate (MPA) or a short protocol for controlled ovarian hyperstimulation (COH) in patients with advanced endometriosis who have normal ovarian function, and to compare cycle characteristics and pregnancy outcomes after frozen-thawed embryo transfer (FET). This was a retrospective case-control study of 244 patients with advanced endometriosis undering COH. The patients were allocated to three groups: the surgery group with MPA COH (62 patients, 71 IVF/ICSI cycles, 78 FET cycles); the aspiration group with MPA COH (85 patients had ovarian “chocolate” cysts (>3 cm) aspirated, 90 IVF/ICSI cycles, 76 FET cycles); and the short protocol group (97 patients, 101 IVF/ICSI cycles, 51 FET cycles). The results showed that higher rates of mature oocyte, D3 high quality embryo, hMG dose were observed in the two study groups using MPA compared with the short protocol. The number of >10–14 mm follicles on the trigger day, D3 top-quality embryos, viable embryos, rates of cancellation, fertilization, implantation, pregnancy outcomes were similar among the three groups. The oocytes, embryos, and pregnancy outcomes were not influenced by endometrioma surgery or presence of endometrioma. MPA COH could be effective for women with ovarian advanced endometriosis who had normal ovarian function.