bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autism spectrum disorders: let’s talk about glucose?
Authors: Hoirisch-Clapauch Silvia , Nardi Antonio E. 
Published: January 2019

AbstractAutism spectrum disorders (ASD) are characterized by disconnectivity due to disordered neuronal migration, and by neuronal mitochondrial dysfunction. Different pathways involved in neuronal migration are affected by intrauterine hyperglycemia and hyperinsulinemia, while prolonged neonatal hypoglycemia may cause mitochondrial dysfunction. Our hypothesis was that conditions leading to intrauterine hyperglycemia or neonatal hypoglycemia would influence ASD pathogenesis. In this study, we identified risk factors for ASD by searching PubMed with the MeSH terms “autism spectrum disorder” and “risk factors”. We then analyzed the relationship between the risk factors and glucose abnormalities in the mother and the offspring. The relationship between glucose abnormalities and risk factors such as obesity, excessive maternal weight gain, or diabetes mellitus is evident. For risk factors such as malformations or exposure to selective serotonin reuptake inhibitors, the relationship is speculative. In rodents, for example, intrauterine hyperglycemia is associated with malformations, independent of maternal diabetes. In their turn, selective serotonin reuptake inhibitors reduce the signs of neonatal hypoglycemia. Going undetected, prolonged hypoglycemia may harm the neonatal brain. Importantly, our group demonstrated that either high-carbohydrate diets or physical inactivity the day before delivery may influence neonatal glycemia. In that study, of 158 neonates selected to be screened according to maternal lifestyle risk factors, 48 had hypoglycemia. Of note, five of them had not been identified with current screening programs. Controlled studies are needed to clarify whether maternal interventions aiming at maintaining glycemic control, together with screening programs for neonatal hypoglycemia based on maternal lifestyle risk factors and on exposure to specific prenatal medications can reduce the prevalence of ASD.
Transethnic meta-analysis of rare coding variants in PLCG2, ABI3, and TREM2 supports their general contribution to Alzheimer’s disease
Authors: Dalmasso Maria Carolina , Brusco Luis Ignacio , Olivar Natividad , Muchnik Carolina , Hanses Claudia , Milz Esther , Becker Julian , Heilmann-Heimbach Stefanie , Hoffmann Per , Prestia Federico A. , Galeano Pablo , Avalos Mariana Soledad Sanchez , Martinez Luis Eduardo , Carulla Mariana Estela , Azurmendi Pablo Javier , Liberczuk Cynthia , Fezza Cristina , Sampaño Marcelo , Fierens Maria , Jemar Guillermo , Solis Patricia , Medel Nancy , Lisso Julieta , Sevillano Zulma , Bosco Paolo , Bossù Paola , Spalletta Gianfranco , Galimberti Daniela , Mancuso Michelangelo , Nacmias Benedetta , Sorbi Sandro , Mecocci Patrizia , Pilotto Alberto , Caffarra Paolo , Panza Francesco , Bullido Maria , Clarimon Jordi , Sánchez-Juan Pascual , Coto Eliecer , Sanchez-Garcia Florentino , Graff Caroline , Ingelsson Martin , Bellenguez Céline , Castaño Eduardo Miguel , Kairiyama Claudia , Politis Daniel Gustavo , Kochen Silvia , Scaro Horacio , Maier Wolfgang , Jessen Frank , Mangone Carlos Alberto , Lambert Jean-Charles , Morelli Laura , Ramirez Alfredo 
Published: January 2019

AbstractRare coding variants in TREM2, PLCG2, and ABI3 were recently associated with the susceptibility to Alzheimer’s disease (AD) in Caucasians. Frequencies and AD-associated effects of variants differ across ethnicities. To start filling the gap on AD genetics in South America and assess the impact of these variants across ethnicity, we studied these variants in Argentinian population in association with ancestry. TREM2 (rs143332484 and rs75932628), PLCG2 (rs72824905), and ABI3 (rs616338) were genotyped in 419 AD cases and 486 controls. Meta-analysis with European population was performed. Ancestry was estimated from genome-wide genotyping results. All variants show similar frequencies and odds ratios to those previously reported. Their association with AD reach statistical significance by meta-analysis. Although the Argentinian population is an admixture, variant carriers presented mainly Caucasian ancestry. Rare coding variants in TREM2, PLCG2, and ABI3 also modulate susceptibility to AD in populations from Argentina, and they may have a European heritage.
TBL1 is required for the mesenchymal phenotype of transformed breast cancer cells
Authors: Rivero Sabrina , Gómez-Marín Elena , Guerrero-Martínez José A. , García-Martínez Jorge , Reyes José C. 
Published: January 2019

AbstractThe epithelial-to-mesenchymal transition (EMT) and its reversion (MET) are related to tumor cell dissemination and migration, tumor circulating cell generation, cancer stem cells, chemoresistance, and metastasis formation. To identify chromatin and epigenetic factors possibly involved in the process of EMT, we compare the levels of expression of epigenetic genes in a transformed human breast epithelial cell line (HMEC-RAS) versus a stable clone of the same cell line expressing the EMT master regulator ZEB1 (HMEC-RAS-ZEB1). One of the factors strongly induced in the HMEC-RAS-ZEB1 cells was Transducin beta-like 1 (TBL1), a component of the NCoR complex, which has both corepressor and coactivator activities. We show that TBL1 interacts with ZEB1 and that both factors cooperate to repress the promoter of the epithelial gene E-cadherin (CDH1) and to autoactivate the ZEB1 promoter. Consistent with its central role, TBL1 is required for mesenchymal phenotypes of transformed breast epithelial and breast cancer cell lines of the claudin-low subtype. Importantly, a high expression of the TBL1 gene correlates with poor prognosis and increased proportion of metastasis in breast cancer patients, indicating that the level of TBL1 expression can be used as a prognostic marker.
Promoter-proximal pausing mediated by the exon junction complex regulates splicing
Authors: Akhtar Junaid , Kreim Nastasja , Marini Federico , Mohana Giriram , Brüne Daniel , Binder Harald , Roignant Jean-Yves 
Published: January 2019

AbstractPromoter-proximal pausing of RNA polymerase II (Pol II) is a widespread transcriptional regulatory step across metazoans. Here we find that the nuclear exon junction complex (pre-EJC) is a critical and conserved regulator of this process. Depletion of pre-EJC subunits leads to a global decrease in Pol II pausing and to premature entry into elongation. This effect occurs, at least in part, via non-canonical recruitment of pre-EJC components at promoters. Failure to recruit the pre-EJC at promoters results in increased binding of the positive transcription elongation complex (P-TEFb) and in enhanced Pol II release. Notably, restoring pausing is sufficient to rescue exon skipping and the photoreceptor differentiation defect associated with depletion of pre-EJC components in vivo. We propose that the pre-EJC serves as an early transcriptional checkpoint to prevent premature entry into elongation, ensuring proper recruitment of RNA processing components that are necessary for exon definition.
Functional role of PGAM5 multimeric assemblies and their polymerization into filaments
Authors: Ruiz Karen , Thaker Tarjani M. , Agnew Christopher , Miller-Vedam Lakshmi , Trenker Raphael , Herrera Clara , Ingaramo Maria , Toso Daniel , Frost Adam , Jura Natalia 
Published: January 2019

AbstractPGAM5 is a mitochondrial protein phosphatase whose genetic ablation in mice results in mitochondria-related disorders, including neurodegeneration. Functions of PGAM5 include regulation of mitophagy, cell death, metabolism and aging. However, mechanisms regulating PGAM5 activation and signaling are poorly understood. Using electron cryo-microscopy, we show that PGAM5 forms dodecamers in solution. We also present a crystal structure of PGAM5 that reveals the determinants of dodecamer formation. Furthermore, we observe PGAM5 dodecamer assembly into filaments both in vitro and in cells. We find that PGAM5 oligomerization into a dodecamer is not only essential for catalytic activation, but this form also plays a structural role on mitochondrial membranes, which is independent of phosphatase activity. Together, these findings suggest that modulation of the oligomerization of PGAM5 may be a regulatory switch of potential therapeutic interest.
Reductions in prefrontal activation predict off-topic utterances during speech production
Authors: Hoffman Paul 
Published: January 2019

AbstractThe ability to speak coherently is essential for effective communication but declines with age: older people more frequently produce tangential, off-topic speech. Little is known, however, about the neural systems that support coherence in speech production. Here, fMRI was used to investigate extended speech production in healthy older adults. Computational linguistic analyses were used to quantify the coherence of utterances produced in the scanner, allowing identification of the neural correlates of coherence for the first time. Highly coherent speech production was associated with increased activity in bilateral inferior prefrontal cortex (BA45), an area implicated in selection of task-relevant knowledge from semantic memory, and in bilateral rostrolateral prefrontal cortex (BA10), implicated more generally in planning of complex goal-directed behaviours. These findings demonstrate that neural activity during spontaneous speech production can be predicted from formal analysis of speech content, and that multiple prefrontal systems contribute to coherence in speech.
Anticancer polymers designed for killing dormant prostate cancer cells
Authors: Takahashi Haruko , Yumoto Kenji , Yasuhara Kazuma , Nadres Enrico T. , Kikuchi Yutaka , Buttitta Laura , Taichman Russell S. , Kuroda Kenichi 
Published: January 2019

AbstractThe discovery of anticancer therapeutics effective in eliminating dormant cells is a significant challenge in cancer biology. Here, we describe new synthetic polymer-based anticancer agents that mimic the mode of action of anticancer peptides. These anticancer polymers developed here are designed to capture the cationic, amphiphilic traits of anticancer peptides. The anticancer polymers are designed to target anionic lipids exposed on the cancer cell surfaces and act by disrupting the cancer cell membranes. Because the polymer mechanism is not dependent on cell proliferation, we hypothesized that the polymers were active against dormant cancer cells. The polymers exhibited cytotoxicity to proliferating prostate cancer. Importantly, the polymer killed dormant prostate cancer cells that were resistant to docetaxel. This study demonstrates a new approach to discover novel anticancer therapeutics.
Advanced measurement and diagnosis of the effect on the underlayer roughness for industrial standard metrology
Authors: Kim Jung-Hwan , Moon Seunghyun , Kim Ji-Woong , Lee Donggun , Park Byong Chon , Kim Dal-Hyun , Jeong Yoojin , Hand Sean , Osborne Jason , De Wolf Peter , Kim Youn Sang , Shin ChaeHo 
Published: January 2019

AbstractIn current nanoscale semiconductor fabrications, high dielectric materials and ultrathin multilayers have been selected to improve the performance of the devices. Thus, interface effects between films and the quantification of surface information are becoming key issues for determining the performance of the semiconductor devices. In this paper, we developed an easy, accurate, and nondestructive diagnosis to investigate the interface effect of hafnium oxide ultrathin films. A roughness scaling method that artificially modified silicon surfaces with a maximum peak-to-valley roughness range of a few nanometers was introduced to examine the effect on the underlayer roughness. The critical overlayer roughness was be defined by the transition of RMS roughness which was 0.18 nm for the 3 nm thick hafnium oxide film. Subsequently, for the inline diagnostic application of semiconductor fabrication, the roughness of a mass produced hafnium film was investigated. Finally, we confirmed that the result was below the threshold set by our critical roughness. The RMS roughness of the mass produced hafnium oxide film was 0.11 nm at a 500 nm field of view. Therefore, we expect that the quantified and standardized critical roughness managements will contribute to improvement of the production yield.
Studying the regression profiles of cervical tumours during radiotherapy treatment using a patient-specific multiscale model
Authors: Kyroudis Christos A. , Dionysiou Dimitra D. , Kolokotroni Eleni A. , Stamatakos Georgios S. 
Published: January 2019

AbstractApart from offering insight into the biomechanisms involved in cancer, many recent mathematical modeling efforts aspire to the ultimate goal of clinical translation, wherein models are designed to be used in the future as clinical decision support systems in the patient-individualized context. Most significant challenges are the integration of multiscale biodata and the patient-specific model parameterization. A central aim of this study was the design of a clinically-relevant parameterization methodology for a patient-specific computational model of cervical cancer response to radiotherapy treatment with concomitant cisplatin, built around a tumour features-based search of the parameter space. Additionally, a methodological framework for the predictive use of the model was designed, including a scoring method to quantitatively reflect the similarity and bilateral predictive ability of any two tumours in terms of their regression profile. The methodology was applied to the datasets of eight patients. Tumour scenarios in accordance with the available longitudinal data have been determined. Predictive investigations identified three patient cases, anyone of which can be used to predict the volumetric evolution throughout therapy of the tumours of the other two with very good results. Our observations show that the presented approach is promising in quantifiably differentiating tumours with distinct regression profiles.
Transient increase of activated regulatory T cells early after kidney transplantation
Authors: Mederacke Young-Seon , Vondran Florian W. , Kollrich Sonja , Schulde Elvira , Schmitt Roland , Manns Michael P. , Klempnauer Jürgen , Schwinzer Reinhard , Noyan Fatih , Jaeckel Elmar 
Published: January 2019

AbstractRegulatory T cells (Tregs) are crucial in controlling allospecific immune responses. However, studies in human kidney recipients regarding the contribution of polyspecific Tregs have provided differing results and studies on alloreactive Tregs are missing completely. In this retrospective study, we specifically analyzed activated CD4+CD25highFOXP3+GARP+Tregs in 17 patients of a living donor kidney transplantation cohort longitudinally over 24 months by flow cytometry (FOXP3: forkhead box protein 3, GARP: glycoprotein A repetitions predominant). We could demonstrate that Tregs of patients with end-stage renal disease (ESRD) are already pre-activated when compared to healthy controls. Furthermore, even though total CD4+CD25highFOXP3+Treg numbers decreased in the first three months after transplantation, frequency of activated Tregs increased significantly representing up to 40% of all peripheral Tregs. In a cohort of living donor kidney transplantation recipients with stable graft function, frequencies of activated Tregs did not correlate with the occurrence of acute cellular rejection or chronic graft dysfunction. Our results will be important for clinical trials using adoptive Treg therapy after kidney transplantation. Adoptively transferred Tregs could be important to compensate the Treg loss at month 3, while they have to compete within the Treg niche with a large number of activated Tregs.
Finding new grain forms in three dimensions
Authors: Wang Hao , Xue Weihua , Feng Minnan , Liu Guoquan 
Published: January 2019

AbstractTopological grain forms in three dimensions are studied experimentally and by large-scale Potts model Monte Carlo simulation. Some new band-faced grain forms are firstly observed among 16,254 pure iron grains, yet none of them is found among 28,049 Monte Carlo simulation grains, which indicate that there is shorter residence times for band-faced grain forms in three dimensions. The combined curvature/topology analysis suggests a possible efficient way of topological transitions of grain forms which is different from the known transition paths.
Proteinaceous Nano container Encapsulate Polycyclic Aromatic Hydrocarbons
Authors: McDougall Matthew , Francisco Olga , Harder-Viddal Candice , Roshko Roy , Heide Fabian , Sidhu Shubleen , Khajehpour Mazdak , Leslie Jennifer , Palace Vince , Tomy Gregg T. , Stetefeld Jörg 
Published: January 2019

AbstractPolycyclic aromatic hydrocarbons (PAHs) are toxic, mutagenic and among the most damaging chemical compounds with regard to living organisms. Because of their persistence and wide distribution removal from the environment is an important challenge. Here we report a new Nano container matrix based on the deep sea archaea-derived RHCC-Nanotube (RHCC-NT), which rapidly and preferentially binds low molecular weight PAHs. Under controlled-laboratory conditions and using fluorescence spectroscopy in combination with X-ray crystallography and MD simulations, we quantified the real-time binding of low molecular weight PAHs (2–4 rings) to our substrate. Binding coefficients ranged from 5.4 ± 1.6 (fluorene) to 32 ± 7.0 μM (acenaphthylene) and a binding capacity of 85 pmoles PAH per mg RHCC-NT, or 2.12 μmoles in a standard 25 mg sampler. The uptake rate of pyrene was calculated to be 1.59 nmol/hr∙mol RHCC-NT (at 10  C). Our results clearly show that RHCC-NT is uniquely suited as a monitoring matrix for low molecular weight PAHs.
Multi-Channel 3D Deep Feature Learning for Survival Time Prediction of Brain Tumor Patients Using Multi-Modal Neuroimages
Authors: Nie Dong , Lu Junfeng , Zhang Han , Adeli Ehsan , Wang Jun , Yu Zhengda , Liu LuYan , Wang Qian , Wu Jinsong , Shen Dinggang 
Published: January 2019

AbstractHigh-grade gliomas are the most aggressive malignant brain tumors. Accurate pre-operative prognosis for this cohort can lead to better treatment planning. Conventional survival prediction based on clinical information is subjective and could be inaccurate. Recent radiomics studies have shown better prognosis by using carefully-engineered image features from magnetic resonance images (MRI). However, feature engineering is usually time consuming, laborious and subjective. Most importantly, the engineered features cannot effectively encode other predictive but implicit information provided by multi-modal neuroimages. We propose a two-stage learning-based method to predict the overall survival (OS) time of high-grade gliomas patient. At the first stage, we adopt deep learning, a recently dominant technique of artificial intelligence, to automatically extract implicit and high-level features from multi-modal, multi-channel preoperative MRI such that the features are competent of predicting survival time. Specifically, we utilize not only contrast-enhanced T1 MRI, but also diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI), for computing multiple metric maps (including various diffusivity metric maps derived from DTI, and also the frequency-specific brain fluctuation amplitude maps and local functional connectivity anisotropy-related metric maps derived from rs-fMRI) from 68 high-grade glioma patients with different survival time. We propose a multi-channel architecture of 3D convolutional neural networks (CNNs) for deep learning upon those metric maps, from which high-level predictive features are extracted for each individual patch of these maps. At the second stage, those deeply learned features along with the pivotal limited demographic and tumor-related features (such as age, tumor size and histological type) are fed into a support vector machine (SVM) to generate the final prediction result (i.e., long or short overall survival time). The experimental results demonstrate that this multi-model, multi-channel deep survival prediction framework achieves an accuracy of 90.66%, outperforming all the competing methods. This study indicates highly demanded effectiveness on prognosis of deep learning technique in neuro-oncological applications for better individualized treatment planning towards precision medicine.
Evolution of sex determination and heterogamety changes in section Otites of the genus Silene
Authors: Balounova Veronika , Gogela Roman , Cegan Radim , Cangren Patrik , Zluvova Jitka , Safar Jan , Kovacova Viera , Bergero Roberta , Hobza Roman , Vyskot Boris , Oxelman Bengt , Charlesworth Deborah , Janousek Bohuslav 
Published: January 2019

AbstractSwitches in heterogamety are known to occur in both animals and plants. Although plant sex determination systems probably often evolved more recently than those in several well-studied animals, including mammals, and have had less time for switches to occur, we previously detected a switch in heterogamety in the plant genus Silene: section Otites has both female and male heterogamety, whereas S. latifolia and its close relatives, in a different section of the genus, Melandrium (subgenus Behenantha), all have male heterogamety. Here we analyse the evolution of sex chromosomes in section Otites, which is estimated to have evolved only about 0.55 MYA. Our study confirms female heterogamety in S. otites and newly reveals female heterogamety in S. borysthenica. Sequence analyses and genetic mapping show that the sex-linked regions of these two species are the same, but the region in S. colpophylla, a close relative with male heterogamety, is different. The sex chromosome pairs of S. colpophylla and S. otites each correspond to an autosome of the other species, and both differ from the XY pair in S. latifolia. Silene section Otites species are suitable for detailed studies of the events involved in such changes, and our phylogenetic analysis suggests a possible change from female to male heterogamety within this section. Our analyses suggest a possibility that has so far not been considered, change in heterogamety through hybridization, in which a male-determining chromosome from one species is introgressed into another one, and over-rides its previous sex-determining system.
Protecting quantum correlations of the XXZ model by topological boundary conditions
Authors: Zeng Shi-Ping , Shi Hai-Long , Zhou Xu , Wang Xiao-Hui , Liu Si-Yuan , Hu Ming-Liang 
Published: January 2019

AbstractThe differences between the XXZ model with topological and periodical boundary conditions were compared by studying their entanglement, quantum discord, and critical temperature above which the entanglement vanishes. It shows that the different boundary conditions mainly affect bipartite quantum correlations of the boundary spins rather than that of other spin pairs. The topological boundary spins can protect entanglement and discord against strong magnetic fields while the periodical boundary spins can protect them against nonuniform magnetic fields. Compared with the periodical XXZ model, the critical temperature is significantly improved for the topological XXZ model. The topological XXZ model also allows us to improve significantly its critical temperature by increasing the strength of magnetic field, which is not feasible for the periodical XXZ model. It is therefore more promising for preparing entangled states at high temperature in the topological XXZ model.