bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered levels of dopamine transporter in the frontal pole and dorsal striatum in schizophrenia
Authors: Sekiguchi Hirotaka , Pavey Geoff , Dean Brian 
Published: December 2019

AbstractThe dopamine hypothesis proposes that there is a hypodopaminergic state in the prefrontal cortex and a hyperdopaminergic state in the striatum of patients with schizophrenia. Evidence suggests the hyperdopaminergic state in the striatum is due to synaptic dopamine elevation, particularly in the dorsal striatum. However, the molecular mechanisms causing disrupted dopaminergic function in schizophrenia remains unclear. We postulated that the dopamine transporter (DAT), which regulates intra-synaptic dopamine concentrations by transporting dopamine from the synaptic cleft into the pre-synaptic neuron, could be involved in dopaminergic dysfunction in schizophrenia. Therefore, we measured levels of DAT in the cortex and striatum from patients with schizophrenia and controls using postmortem human brain tissue. Levels of desmethylimipramine-insensitive mazindol-sensitive [3H]mazindol binding to DAT were measured using in situ radioligand binding and autoradiography in gray matter from Brodmann’s area (BA) 10, BA 17, the dorsal striatum, and nucleus accumbens from 15 patients with schizophrenia and 15 controls. Levels of desmethylimipramine-insensitive mazindol-sensitive [3H]mazindol binding were significantly higher in BA 10 from patients with schizophrenia (p = 0.004) and significantly lower in the dorsal striatum (dorsal putamen p = 0.005; dorsal caudate p = 0.007) from those with the disorder. There were no differences in levels of desmethylimipramine-insensitive [3H]mazindol binding in BA 17 or nucleus accumbens. These data raise the possibility that high levels of DAT in BA 10 could be contributing to lower synaptic cortical dopamine, whereas lower levels of DAT could be contributing to a hyperdopaminergic state in the dorsal striatum.
A low-carbohydrate ketogenic diet induces the expression of very-low-density lipoprotein receptor in liver and affects its associated metabolic abnormalities
Authors: Okuda Tetsuya 
Published: December 2019

AbstractA low-carbohydrate ketogenic diet (LCKD) promotes the progression of hepatic steatosis in C57BL/6 wild-type mice, but improves the condition in leptin-deficient obese (ob/ob) mice. Here, we show a novel effect of LCKD associated with the conflicting effects on these mice. Gene expression microarray analyses showed that expression of the Vldlr gene, which encodes the very-low-density lipoprotein receptor (VLDLR), was induced in LCKD-fed ob/ob mice. Although the VLDLR is not normally expressed in the liver, the LCKD led to VLDLR expression in both ob/ob and wild-type mice. To clarify this effect on VLDL dynamics, we analyzed the lipid content of serum lipoproteins and found a marked decrease in VLDL-triglycerides only in LCKD-fed wild-type mice. Further analyses suggested that transport of triglycerides via VLDL from the liver to extrahepatic tissues was inhibited by LCKD-induced hepatic VLDLR expression, but rescued under conditions of leptin deficiency.
Brain activity links performance in science reasoning with conceptual approach
Authors: Bartley Jessica E. , Riedel Michael C. , Salo Taylor , Boeving Emily R. , Bottenhorn Katherine L. , Bravo Elsa I. , Odean Rosalie , Nazareth Alina , Laird Robert W. , Sutherland Matthew T. , Pruden Shannon M. , Brewe Eric , Laird Angela R. 
Published: December 2019

AbstractUnderstanding how students learn is crucial for helping them succeed. We examined brain function in 107 undergraduate students during a task known to be challenging for many students—physics problem solving—to characterize the underlying neural mechanisms and determine how these support comprehension and proficiency. Further, we applied module analysis to response distributions, defining groups of students who answered by using similar physics conceptions, and probed for brain differences linked with different conceptual approaches. We found that integrated executive, attentional, visual motion, and default mode brain systems cooperate to achieve sequential and sustained physics-related cognition. While accuracy alone did not predict brain function, dissociable brain patterns were observed when students solved problems by using different physics conceptions, and increased success was linked to conceptual coherence. Our analyses demonstrate that episodic associations and control processes operate in tandem to support physics reasoning, offering potential insight to support student learning.
Integrative molecular and clinical modeling of clinical outcomes to PD1 blockade in patients with metastatic melanoma
Authors: Liu David , Schilling Bastian , Liu Derek , Sucker Antje , Livingstone Elisabeth , Jerby-Arnon Livnat , Zimmer Lisa , Gutzmer Ralf , Satzger Imke , Loquai Carmen , Grabbe Stephan , Vokes Natalie , Margolis Claire A. , Conway Jake , He Meng Xiao , Elmarakeby Haitham , Dietlein Felix , Miao Diana , Tracy Adam , Gogas Helen , Goldinger Simone M. , Utikal Jochen , Blank Christian U. , Rauschenberg Ricarda , von Bubnoff Dagmar , Krackhardt Angela , Weide Benjamin , Haferkamp Sebastian , Kiecker Felix , Izar Ben , Garraway Levi , Regev Aviv , Flaherty Keith , Paschen Annette , Van Allen Eliezer M. , Schadendorf Dirk 
Published: December 2019

AbstractImmune-checkpoint blockade (ICB) has demonstrated efficacy in many tumor types, but predictors of responsiveness to anti-PD1 ICB are incompletely characterized. In this study, we analyzed a clinically annotated cohort of patients with melanoma (n = 144) treated with anti-PD1 ICB, with whole-exome and whole-transcriptome sequencing of pre-treatment tumors. We found that tumor mutational burden as a predictor of response was confounded by melanoma subtype, whereas multiple novel genomic and transcriptomic features predicted selective response, including features associated with MHC-I and MHC-II antigen presentation. Furthermore, previous anti-CTLA4 ICB exposure was associated with different predictors of response compared to tumors that were naive to ICB, suggesting selective immune effects of previous exposure to anti-CTLA4 ICB. Finally, we developed parsimonious models integrating clinical, genomic and transcriptomic features to predict intrinsic resistance to anti-PD1 ICB in individual tumors, with validation in smaller independent cohorts limited by the availability of comprehensive data. Broadly, we present a framework to discover predictive features and build models of ICB therapeutic response.
Structural genomics applied to the rust fungus Melampsora larici-populina reveals two candidate effector proteins adopting cystine knot and NTF2-like protein folds
Authors: de Guillen Karine , Lorrain Cécile , Tsan Pascale , Barthe Philippe , Petre Benjamin , Saveleva Natalya , Rouhier Nicolas , Duplessis Sébastien , Padilla André , Hecker Arnaud 
Published: December 2019

AbstractRust fungi are plant pathogens that secrete an arsenal of effector proteins interfering with plant functions and promoting parasitic infection. Effectors are often species-specific, evolve rapidly, and display low sequence similarities with known proteins. How rust fungal effectors function in host cells remains elusive, and biochemical and structural approaches have been scarcely used to tackle this question. In this study, we produced recombinant proteins of eleven candidate effectors of the leaf rust fungus Melampsora larici-populina in Escherichia coli. We successfully purified and solved the three-dimensional structure of two proteins, MLP124266 and MLP124017, using NMR spectroscopy. Although both MLP124266 and MLP124017 show no sequence similarity with known proteins, they exhibit structural similarities to knottins, which are disulfide-rich small proteins characterized by intricate disulfide bridges, and to nuclear transport factor 2-like proteins, which are molecular containers involved in a wide range of functions, respectively. Interestingly, such structural folds have not been reported so far in pathogen effectors, indicating that MLP124266 and MLP124017 may bear novel functions related to pathogenicity. Our findings show that sequence-unrelated effectors can adopt folds similar to known proteins, and encourage the use of biochemical and structural approaches to functionally characterize effector candidates.
A Computational Method to Quantify the Effects of Slipped Strand Mispairing on Bacterial Tetranucleotide Repeats
Authors: Harhay Gregory P. , Harhay Dayna M. , Bono James L. , Capik Sarah F. , DeDonder Keith D. , Apley Michael D. , Lubbers Brian V. , White Bradley J. , Larson Robert L. , Smith Timothy P. L. 
Published: December 2019

AbstractThe virulence and pathogenicity of bacterial pathogens are related to their adaptability to changing environments. One process enabling adaptation is based on minor changes in genome sequence, as small as a few base pairs, within segments of genome called simple sequence repeats (SSRs) that consist of multiple copies of a short sequence (from one to several nucleotides), repeated in series. SSRs are found in eukaryotes as well as prokaryotes, and length variation in them occurs at frequencies up to a million-fold higher than bacterial point mutations through the process of slipped strand mispairing (SSM) by DNA polymerase during replication. The characterization of SSR length by standard sequencing methods is complicated by the appearance of length variation introduced during the sequencing process that obscures the lower abundance repeat number variants in a population. Here we report a computational approach to correct for sequencing process-induced artifacts, validated for tetranucleotide repeats by use of synthetic constructs of fixed, known length. We apply this method to a laboratory culture of Histophilus somni, prepared from a single colony, and demonstrate that the culture consists of populations of distinct sequence phase and length variants at individual tetranucleotide SSR loci.
Identification of the amino acid residue responsible for the myricetin sensitivity of human proton-coupled folate transporter
Authors: Yamashiro Takahiro , Yasujima Tomoya , Ohta Kinya , Inoue Katsuhisa , Yuasa Hiroaki 
Published: December 2019

AbstractHuman proton-coupled folate transporter (hPCFT/SLC46A1) has recently been found to be inhibited by myricetin by a sustained mechanism, raising a concern that the inhibition might lead to malabsorption of folates in the intestine, where hPCFT works for their epithelial uptake. However, rat PCFT (rPCFT) has more recently been found not to be inhibited by myricetin. Prompted by this finding, we attempted to determine the amino acid residue involved in that by analyses comparing between hPCFT and rPCFT. In the initial analysis, chimeric constructs prepared from hPCFT and rPCFT were examined for myricetin sensitivity to determine the hPCFT segment involved in the sensitivity. Focusing on the thereby determined segment from 83rd to 186th amino acid residue, hPCFT mutants having a designated amino acid residue replaced with its counterpart in rPCFT were prepared for the subsequent analysis. Among them, only G158N-substituted hPCFT was found to be transformed to be insensitive to myricetin and, accordingly, oppositely N158G-substituted rPCFT was transformed to be sensitive to myricetin. These results indicate the critical role of Gly158 in the myricetin sensitivity of hPCFT. This finding would help advance the elucidation of the mechanism of the myricetin-induced inhibition of hPCFT and manage the potential risk arising from that.
Hemocyte-hemocyte adhesion by granulocytes is associated with cellular immunity in the cricket, Gryllus bimaculatus
Authors: Cho Youngwoo , Cho Saeyoull 
Published: December 2019

AbstractIn this study, more than 1,000 cricket (Gryllus bimaculatus) hemocytes were classified based on their size and morphology. These hemocytes were classified into six types: granulocytes, plasmatocytes, prohemocytes, spherulocytes, coagulocytes, and oenocytoids. Hemocyte cultures was observed in real time to determine which hemocytes were associated with cellular immune responses against potential pathogens. Granulocytes were identified as the professional immune cell that mediates nodulation, encapsulation, and phagocytosis of pathogens. Granulocytes have been shown to actively produce various sticky nets (amoeba-like hairs and extracellular traps) from their plasma membranes that they use to gather other hemocytes and to implement cellular immune responses. The activation of lysosomes in granulocytes started at 4 h, peaked at 12 h, and returned to baseline by 24 h post-infection. At 48 h post-infection, cells could be found within the cytoplasm of granulocytes and reactivated lysosomes surrounding these cells were visible. This result seems to reflect a phenomenon in which necrotic granulocytes are removed by other healthy granulocytes. This unique mechanism of cellular immunity is therefore a way to efficiently and effectively remove pathogens and simultaneously maintain healthy hemocytes.
TSLRF: Two-Stage Algorithm Based on Least Angle Regression and Random Forest in genome-wide association studies
Authors: Sun Jiali , Wu Qingtai , Shen Dafeng , Wen Yangjun , Liu Fengrong , Gao Yu , Ding Jie , Zhang Jin 
Published: December 2019

AbstractOne of the most important tasks in genome-wide association analysis (GWAS) is the detection of single-nucleotide polymorphisms (SNPs) which are related to target traits. With the development of sequencing technology, traditional statistical methods are difficult to analyze the corresponding high-dimensional massive data or SNPs. Recently, machine learning methods have become more popular in high-dimensional genetic data analysis for their fast computation speed. However, most of machine learning methods have several drawbacks, such as poor generalization ability, over-fitting, unsatisfactory classification and low detection accuracy. This study proposed a two-stage algorithm based on least angle regression and random forest (TSLRF), which firstly considered the control of population structure and polygenic effects, then selected the SNPs that were potentially related to target traits by using least angle regression (LARS), furtherly analyzed this variable subset using random forest (RF) to detect quantitative trait nucleotides (QTNs) associated with target traits. The new method has more powerful detection in simulation experiments and real data analyses. The results of simulation experiments showed that, compared with the existing approaches, the new method effectively improved the detection ability of QTNs and model fitting degree, and required less calculation time. In addition, the new method significantly distinguished QTNs and other SNPs. Subsequently, the new method was applied to analyze five flowering-related traits in Arabidopsis. The results showed that, the distinction between QTNs and unrelated SNPs was more significant than the other methods. The new method detected 60 genes confirmed to be related to the target trait, which was significantly higher than the other methods, and simultaneously detected multiple gene clusters associated with the target trait.
Sustainable synthesis of graphene-based adsorbent using date syrup
Authors: Khan Shaihroz , Achazhiyath Edathil Anjali , Banat Fawzi 
Published: December 2019

AbstractHere we demonstrate, a facile in-situ strategy for the synthesis of environmentally benign and scalable graphene sand hybrid using date syrup as a sustainable carbon source through pyrolysis at 750 °C. Raman and SEM images revealed that the as-prepared date syrup-based graphene sand hybrid (D-GSH) had imperfections with macroporous 2-D graphene sheet-like structures stacked on the inorganic sand support. The applicability of the D-GSH for decontaminating the water from cationic (Methyl Violet, MV) and anionic (Congo Red, CR) dye and heavy metals (Pb2+ and Cd2+) was tested. Batch experiments demonstrated that D-GSH showcased exceptional capability for both dye and heavy metals removal with fast adsorption following pseudo-second-order kinetics. The adsorption capacities for MV, Pb2+, and Cd2+ were respectively 2564, 781 and 793 mg/g at 25 °C, the highest capacity graphene-based adsorbent reported in the literature to date. In addition, D-GSH also exhibited high adsorption capacity for anionic dye, CR (333 mg g−1) and good recyclability (3 cycles) for all the contaminants. The thermodynamic studies further confirmed that the adsorption of all contaminants was thermodynamically feasible, spontaneous and endothermic with ∆H° of 48.38, 89.10, 16.89 and 14.73 kJ/mol for MV, CR, Pb2+ and Cd2+, respectively. Thus, utilization of a simple one-step strategy to produce graphenic sand hybrid using date syrup helped in developing a cost-effective and environmentally friendly dye and heavy metal scavenger that can be used as a one-step solution for water decontamination.
Estimating Rates of Progression and Predicting Future Visual Fields in Glaucoma Using a Deep Variational Autoencoder
Authors: Berchuck Samuel I. , Mukherjee Sayan , Medeiros Felipe A. 
Published: December 2019

AbstractIn this manuscript we develop a deep learning algorithm to improve estimation of rates of progression and prediction of future patterns of visual field loss in glaucoma. A generalized variational auto-encoder (VAE) was trained to learn a low-dimensional representation of standard automated perimetry (SAP) visual fields using 29,161 fields from 3,832 patients. The VAE was trained on a 90% sample of the data, with randomization at the patient level. Using the remaining 10%, rates of progression and predictions were generated, with comparisons to SAP mean deviation (MD) rates and point-wise (PW) regression predictions, respectively. The longitudinal rate of change through the VAE latent space (e.g., with eight dimensions) detected a significantly higher proportion of progression than MD at two (25% vs. 9%) and four (35% vs 15%) years from baseline. Early on, VAE improved prediction over PW, with significantly smaller mean absolute error in predicting the 4th, 6thand 8thvisits from the first three (e.g., visit eight: VAE8: 5.14 dB vs. PW: 8.07 dB; P < 0.001). A deep VAE can be used for assessing both rates and trajectories of progression in glaucoma, with the additional benefit of being a generative technique capable of predicting future patterns of visual field damage.
Dynamical Mechanism of Polarons and Bipolarons in Poly(p-Phenylene Vinylene)
Authors: Paula Fábio Luís de Oliveira , Castro Leonardo Luiz e , Junior Luiz Antonio Ribeiro , Júnior Rafael Timóteo de Sousa , Silva Geraldo Magela e , Neto Pedro Henrique de Oliveira 
Published: December 2019

AbstractStudies on Poly(p-Phenylene Vinylene) (PPV) and derivatives have experienced enormous growth since they were successfully used to fabricate the first efficient prototypes of Polymer Light-Emitting Diodes in the 90s. Despite this rapid progress, understanding the relationship between charge transport and the morphology in these materials remains a challenge. Here, we shed light on the understanding of the transport mechanism of polarons and bipolarons in PPVs by developing a two-dimensional tight-binding approach that includes lattice relaxation effects. Remarkably, the results show that the PPV lattice loses the energy related to its conjugation during time by transferring this amount of energy to electrons. Such a process for energy transfer permits the quasiparticles to overcome the potential barrier imposed by the local lattice deformations, that are formed in the presence of an additional charge and, consequently, their electric field assisted transport takes place. Within the framework of this transport mechanism, a better insight into the origin of the carrier mobility in PPV and derivatives can be achieved and would be a useful guide for improving their chemical structures and morphologies.
MicroRNA files in the prevention of intestinal ischemia/reperfusion injury by hydrogen rich saline
Authors: Yao Weifeng , Lin Xiaoyu , Han Xue , Zeng Lanfen , Guo Anshun , Guan Yu , Hei Ziqing , Liu Jianpei , Huang Pinjie 
Published: December 2019

Abstract
Background: Hydrogen-rich saline (HRS) has been proven effective against ischemia/reperfusion (I/R) injury. However, knowledge on the underlying signaling events remain poor. Having recent highlight of microRNAs (miRNAs) in mediating intestinal I/R injury, we hypothesized that HRS may protect intestine against I/R injury by regulating miRNAs.
Method: Mice were given intraperitoneal injection of saline or HRS once daily for five consecutive days before undergoing intestinal I/R that was induced by 60-min ischemia followed by 180-min reperfusion of superior mesenteric artery. The intestine was collected for histopathological assay, miRNA microarray profiling, Real-Time PCR, and Western blotting. Next, miR-199a-3p mimics or inhibitors were transfected into IEC-6 cells to explore the relationship between HRS treatment and miR-199a-3p.
Results: I/R-induced mucosal injury and epithelial cells apoptosis were attenuated by HRS pretreatment. A total of 64 intestinal I/R-responsive miRNAs were altered significantly by HRS pretreatment, in which we validated four novel miRNAs with top significance by Real-Time PCR, namely miR-199a-3p, miR-296-5p, miR-5126, and miR-6538. Particularly, miR-199a-3p was drastically increased by I/R but reduced by HRS. Computational analysis predicts insulin-like growth factor (IGF)-1, mammalian target of rapamycin (mTOR), and phosphoinositide-3-kinase (PI3K) regulatory subunit 1 as targets of miR-199a-3p, suggesting involvement of the pro-survival pathway, IGF- 1/PI3K/Akt/mTOR. In in vitro experiment, HRS treatment reduced miR-199a-3p level, increase IGF-1, PI3K and mTOR mRNA expression, restore IEC-6 cells viability, and this protective effects were reversed under miR-199a-3p mimics treatment.
Conclusion: Collectively, miR-199a-3p may serve a key role in the anti-apoptotic mechanism of HRS that contributes to its protection of the intestine against I/R injury.
P63 modulates the expression of theWDFY2gene which is implicated in cancer regulation and limb development
Authors: Monti Paola , Ciribilli Yari , Foggetti Giorgia , Menichini Paola , Bisio Alessandra , Cappato Serena , Inga Alberto , Divizia Maria Teresa , Lerone Margherita , Bocciardi Renata , Fronza Gilberto 
Published: December 2019

AbstractTP63 is a member of the TP53 gene family, sharing a common gene structure that produces two groups of mRNAs’ encoding proteins with different N-terminal regions (ΔN and TA isoforms); both transcripts are also subjected to alternative splicing mechanisms at C-terminus, generating a variety of isoforms. p63 is a master regulator of epidermal development and homoeostasis as well as an important player in tumorigenesis and cancer progression with both oncogenic and tumour suppressive roles. A number of studies have aimed at the identification of p63 target genes, allowing the dissection of the molecular pathways orchestrated by the different isoforms. In the present study we investigated in more detail the p63 responsiveness of the WDFY2 (WD repeat and FYVE domain containing 2) gene, encoding for an endosomal protein identified as a binding partner of the PI-3K/AKT signalling pathway. We showed that overexpression of different p63 isoforms was able to induce WDFY2 expression in TP53-null cells. The p63-dependent transcriptional activation was associated with specific response elements (REs) that have been identified by a bioinformatics tool and validated by yeast- and mammal-based assays. Interestingly, to confirm that WDFY2 belongs to the p63 network of cancer regulation, we analysed the impact of WDFY2 alterations, by showing its frequent deletion in different types of tumours and suggesting its expression level as a prognostic biomarker. Lastly, we identified a chromosomal translocation involving the WDFY2 locus in a patient affected by a rare congenital limb anomaly, indicating WDFY2 as a possible susceptibility gene placed downstream p63 in the network of limb development.