bluuebunny/crossref_metadata_2025_split huggingface dataset:
Environmental enrichment shapes striatal spike-timing-dependent plasticity in vivo
Authors: Morera-Herreras Teresa , Gioanni Yves , Perez Sylvie , Vignoud Gaetan , Venance Laurent 
Published: December 2019

AbstractBehavioural experience, such as environmental enrichment (EE), induces long-term effects on learning and memory. Learning can be assessed with the Hebbian paradigm, such as spike-timing-dependent plasticity (STDP), which relies on the timing of neuronal activity on either side of the synapse. Although EE is known to control neuronal excitability and consequently spike timing, whether EE shapes STDP remains unknown. Here, using in vivo long-duration intracellular recordings at the corticostriatal synapses we show that EE promotes asymmetric anti-Hebbian STDP, i.e. spike-timing-dependent-potentiation (tLTP) for post-pre pairings and spike-timing-dependent-depression (tLTD) for pre-post pairings, whereas animals grown in standard housing show mainly tLTD and a high failure rate of plasticity. Indeed, in adult rats grown in standard conditions, we observed unidirectional plasticity (mainly symmetric anti-Hebbian tLTD) within a large temporal window (~200 ms). However, rats grown for two months in EE displayed a bidirectional STDP (tLTP and tLTD depending on spike timing) in a more restricted temporal window (~100 ms) with low failure rate of plasticity. We also found that the effects of EE on STDP characteristics are influenced by the anaesthesia status: the deeper the anaesthesia, the higher the absence of plasticity. These findings establish a central role for EE and the anaesthetic regime in shaping in vivo, a synaptic Hebbian learning rule such as STDP.
Type 2 diabetes-associated single nucleotide polymorphism in Sorcs1 gene results in alternative processing of the Sorcs1 protein in INS1 β-cells
Authors: Yau Belinda , Blood Zachary , An Yousun , Su Zhiduan , Kebede Melkam A. 
Published: December 2019

AbstractA threonine-to-Isoleucine (Thr52Ile) mutation within the pro-domain of the Sorcs1 gene was positionally cloned as the gene underlying a quantitative trait locus that affects fasting insulin levels in mice. In humans, genome-wide association studies and linkage studies have shown that SORCS1 is associated with diabetes and all of diabetes complications. We have recently shown that deletion of Sorcs1 in mice made obese with the leptinob mutation results in diabetes and an insulin granule stability defect. This present study investigates the functional consequence of the Sorcs1 Thr52Ile mutation in the rat INS1 β-cell line expressing either the wildtype or mutant Sorcs1 allele. We find that Sorcs1 Thr52Ile mutation is associated with increased basal insulin secretion, reduced glucose-stimulated insulin secretion and decreased insulin content in INS1 cells. Moreover, expression of Thr52Ile causes differential processing of the Sorcs1 protein resulting in the formation of an additional 90 kDa mutant form of the protein. The mutant form of the protein is localised to the ER, retains its pro-domain, and concurrently reduces expression of the functional mature 130 kDa Sorcs1 protein. These findings provide a mechanistic clue to why this specific allelic variation in Sorcs1 was associated with reduced insulin levels and type 2 diabetes.
Prediction of malignant glioma grades using contrast-enhanced T1-weighted and T2-weighted magnetic resonance images based on a radiomic analysis
Authors: Nakamoto Takahiro , Takahashi Wataru , Haga Akihiro , Takahashi Satoshi , Kiryu Shigeru , Nawa Kanabu , Ohta Takeshi , Ozaki Sho , Nozawa Yuki , Tanaka Shota , Mukasa Akitake , Nakagawa Keiichi 
Published: December 2019

AbstractWe conducted a feasibility study to predict malignant glioma grades via radiomic analysis using contrast-enhanced T1-weighted magnetic resonance images (CE-T1WIs) and T2-weighted magnetic resonance images (T2WIs). We proposed a framework and applied it to CE-T1WIs and T2WIs (with tumor region data) acquired preoperatively from 157 patients with malignant glioma (grade III: 55, grade IV: 102) as the primary dataset and 67 patients with malignant glioma (grade III: 22, grade IV: 45) as the validation dataset. Radiomic features such as size/shape, intensity, histogram, and texture features were extracted from the tumor regions on the CE-T1WIs and T2WIs. The Wilcoxon–Mann–Whitney (WMW) test and least absolute shrinkage and selection operator logistic regression (LASSO-LR) were employed to select the radiomic features. Various machine learning (ML) algorithms were used to construct prediction models for the malignant glioma grades using the selected radiomic features. Leave-one-out cross-validation (LOOCV) was implemented to evaluate the performance of the prediction models in the primary dataset. The selected radiomic features for all folds in the LOOCV of the primary dataset were used to perform an independent validation. As evaluation indices, accuracies, sensitivities, specificities, and values for the area under receiver operating characteristic curve (or simply the area under the curve (AUC)) for all prediction models were calculated. The mean AUC value for all prediction models constructed by the ML algorithms in the LOOCV of the primary dataset was 0.902 ± 0.024 (95% CI (confidence interval), 0.873–0.932). In the independent validation, the mean AUC value for all prediction models was 0.747 ± 0.034 (95% CI, 0.705–0.790). The results of this study suggest that the malignant glioma grades could be sufficiently and easily predicted by preparing the CE-T1WIs, T2WIs, and tumor delineations for each patient. Our proposed framework may be an effective tool for preoperatively grading malignant gliomas.
A Flow Induced Autoimmune Response and Accelerated Senescence of Red Blood Cells in Cardiovascular Devices
Authors: Buerck James P. , Burke Dustin K. , Schmidtke David W. , Snyder Trevor A. , Papavassiliou Dimitrios , O’Rear Edgar A. 
Published: December 2019

AbstractRed blood cells (RBCs) passing through heart pumps, prosthetic heart valves and other cardiovascular devices undergo early senescence attributed to non-physiologic forces. We hypothesized that mechanical trauma accelerates aging by deformation of membrane proteins to cause binding of naturally occurring IgG. RBCs isolated from blood of healthy volunteers were exposed to high shear stress in a viscometer or microfluidics channel to mimic mechanical trauma and then incubated with autologous plasma. Increased binding of IgG was observed indicating forces caused conformational changes in a membrane protein exposing an epitope(s), probably the senescent cell antigen of band 3. The binding of immunoglobulin suggests it plays a role in the premature sequestration and phagocytosis of RBCs in the spleen. Measurement of IgG holds promise as a marker foreshadowing complications in cardiovascular patients and as a means to improve the design of medical devices in which RBCs are susceptible to sublethal trauma.
SHBG141–161 Domain-Peptide Stimulates GPRC6A-Mediated Response in Leydig and β-Langerhans cell lines
Authors: De Toni Luca , Guidolin Diego , De Filippis Vincenzo , Peterle Daniele , Rocca Maria Santa , Di Nisio Andrea , De Rocco Ponce Maurizio , Foresta Carlo 
Published: December 2019

AbstractGPRC6A is acknowledged as a major regulator of energy metabolism and male fertility through the action of undercarboxylated osteocalcin (ucOCN), representing a possible therapeutic target. We recently showed that the sex hormone-binding globulin (SHBG) binds to GPRC6A through the likely involvement of the 141–161 domain. To confirm this model, here we investigated the possible binding and agonist activity of SHBG(141–161) domain-peptide (SHBG141–161) on GPRC6A. The binding of SHBG141–161 to GPRC6A and downstream dissociation from Gαi(GDP) protein was computationally modelled. SHBG141–161 was obtained by solid-phase synthesis, characterized by circular dichroism (CD) and the receptor binding was assessed by displacement of ucOCN on HEK-293 cells transfected with GPRC6A gene. Agonist activity of SHBG141–161 was assessed on Leydig MA-10 and Langerhans β-TC6 cell lines through the GPRC6A-mediated release of testosterone (T) and insulin. SHBG141–161 was predicted to bind to GPRC6A and to reduce the affinity for Gαi(GDP) at computational level. Conformational properties and binding to GPRC6A of the synthetic SHBG141–161 were confirmed by CD and displacement experiments. SHBG141–161 stimulated cell secretion of T and insulin, with dose dependency from 10−13 to 10−11M for T release (respectively P = 0,041 10−13M; P = 0,032 10−12M; P = 0,008 10−11M vs basal) and for 10−12 to 10−10M for insulin (respectively P = 0,041 10−12M; P = 0,007 10−11M; P = 0,047 10−10M; P = 0,045 vs basal). Blockade with anti GPRC6A IgG abolished the response to SHBG141-161, suggesting agonist specificity. SHBG141–161 showed stimulating activity on GPRC6A, representing a template peptide with possible therapeutic use for metabolic and endocrine disorders.
The effect of exercise on intramyocellular acetylcarnitine (AcCtn) concentration in adult growth hormone deficiency (GHD)
Authors: Meienberg Fabian , Loher Hannah , Bucher Julie , Jenni Stefan , Krüsi Marion , Kreis Roland , Boesch Chris , Betz Matthias Johannes , Christ Emanuel 
Published: December 2019

AbstractTo cover increasing energy demands during exercise, tricarboxylic cycle (TCA) flux in skeletal muscle is markedly increased, resulting in the increased formation of intramyocellular acetylcarnitine (AcCtn). We hypothesized that reduced substrate availability within the exercising muscle, reflected by a diminished increase of intramyocellular AcCtn concentration during exercise, might be an underlying mechanism for the impaired exercise performance observed in adult patients with growth hormone deficiency (GHD). We aimed at assessing the effect of 2 hours of moderately intense exercise on intramyocellular AcCtn concentrations, measured by proton magnetic resonance spectroscopy (1H-MRS), in seven adults with GHD compared to seven matched control subjects (CS). Compared to baseline levels AcCtn concentrations significantly increased after 2 hours of exercise, and significantly decreased over the following 24 hours (ANOVA p for effect of time = 0.0023 for all study participants; p = 0.067 for GHD only, p = 0.045 for CS only). AcCtn concentrations at baseline, as well as changes in AcCtn concentrations over time were similar between GHD patients and CS (ANOVA p for group effect = 0.45). There was no interaction between group and time (p = 0.53). Our study suggests that during moderately intense exercise the availability of energy substrate within the exercising muscle is not significantly different in GHD patients compared to CS.
Electrophysiological correlates of the flexible allocation of visual working memory resources
Authors: Salahub Christine , Lockhart Holly A. , Dube Blaire , Al-Aidroos Naseem , Emrich Stephen M. 
Published: December 2019

AbstractVisual working memory is a brief, capacity-limited store of visual information that is involved in a large number of cognitive functions. To guide one’s behavior effectively, one must efficiently allocate these limited memory resources across memory items. Previous research has suggested that items are either stored in memory or completely blocked from memory access. However, recent behavioral work proposes that memory resources can be flexibly split across items based on their level of task importance. Here, we investigated the electrophysiological correlates of flexible resource allocation by manipulating the distribution of resources amongst systematically lateralized memory items. We examined the contralateral delay activity (CDA), a waveform typically associated with the number of items held in memory. Across three experiments, we found that, in addition to memory load, the CDA flexibly tracks memory resource allocation. This allocation occurred as early as attentional selection, as indicated by the N2pc. Additionally, CDA amplitude was better-described when fit with a continuous model predicted by load and resources together than when fit with either alone. Our findings show that electrophysiological markers of attentional selection and memory maintenance not only track memory load, but also the proportion of memory resources those items receive.
Dystrophin and calcium current are decreased in cardiomyocytes expressing Cre enzyme driven by αMHC but not TNT promoter
Authors: Gillet Ludovic , Guichard Sabrina , Essers Maria C. , Rougier Jean-Sébastien , Abriel Hugues 
Published: December 2019

AbstractThe Cre/lox system is a potent technology to control gene expression in mouse tissues. However, cardiac-specific Cre recombinase expression alone can lead to cardiac alterations when no loxP sites are present, which is not well understood. Many loxP-like sites have been identified in the mouse genome that might be Cre sensitive. One of them is located in the Dmd gene encoding dystrophin, a protein important for the function and stabilization of voltage-gated calcium (Cav1.2) and sodium (Nav1.5) channels, respectively. Here, we investigate whether Cre affects dystrophin expression and function in hearts without loxP sites in the genome. In mice expressing Cre under the alpha-myosin heavy chain (MHC-Cre) or Troponin T (TNT-Cre) promoter, we investigated dystrophin expression, Nav1.5 expression, and Cav1.2 function. Compared to age-matched MHC-Cre− mice, dystrophin protein level was significantly decreased in hearts from MHC-Cre+ mice of more than 12-weeks-old. Quantitative RT-PCR revealed decreased mRNA levels of Dmd gene. Unexpectedly, calcium current (ICaL), but not Nav1.5 protein expression was altered in those mice. Surprisingly, in hearts from 12-week-old and older TNT-Cre+ mice, neither ICaL nor dystrophin and Nav1.5 protein content were altered compared to TNT-Cre−. Cre recombinase unpredictably affects cardiac phenotype, and Cre-expressing mouse models should be carefully investigated before experimental use.
TopControl: A Tool to Prioritize Candidate Disease-associated Genes based on Topological Network Features
Authors: Nazarieh Maryam , Helms Volkhard 
Published: December 2019

AbstractPutative disease-associated genes are often identified among those genes that are differentially expressed in disease and in normal conditions. This strategy typically yields thousands of genes. Gene prioritizing schemes boost the power of identifying the most promising disease-associated genes among such a set of candidates. We introduce here a novel system for prioritizing genes where a TF-miRNA co-regulatory network is constructed for the set of genes, while the ranks of the candidates are determined by topological and biological factors. For datasets on breast invasive carcinoma and liver hepatocellular carcinoma this novel prioritization technique identified a significant portion of known disease-associated genes and suggested new candidates which can be investigated later as putative disease-associated genes.
Neuronal and perineuronal changes of cerebral cortex after exposure to inhaled particulate matter
Authors: Kim So Young , Lee Da-hye , Park Sohyeon , Kim Byeong-Gon , Jang An-Soo , Oh Seung Ha , Lee Jun Ho , Suh Myung-Whan , Park Moo Kyun 
Published: December 2019

AbstractThe inhalation of particulate matter (PM) increases the perineuronal nets (PNNs) in the cerebral cortex; however, little is known about the related molecular changes. We explored how PM exposure impacted cognitive function and the levels of PNN-related genes. BALB/c mice (6-week-old females, n = 32) were exposed to 1–5-μm diesel-extracted particles (DEPs) (100 µg/m3, 5 hours per day, 5 days per week) and categorized into the following four groups: 1) 4-week DEP exposure (n = 8); 2) 4-week control (n = 8); 3) 8-week DEP exposure (n = 8); and 4) 8-week control (n = 8). The Y-maze test and olfactory function test were conducted after 4 and 8 weeks of DEP exposure. The prefrontal cortex, olfactory bulb and temporal cortex were harvested from the animals in each group. The expression of genes related to PNNs (Tenascin C, matrix metalloproteinase [MMP]14, MMP9) and synaptic vesicular transporters of vesicular glutamergic transporter 1 (VGLUT1), VGLUT2, vesicular GABAergic transporter (VGAT) were measured. The temporal cortex was immunostained for neurocan, VGLUT1, and VGAT. The 4-week DEP group had lower total arm entry in the Y-maze test and olfactory sensitivity. These impaired behavioral functions recovered in the 8-week DEP group. Expression of tenascin C and MMP9 were increased in the cerebral cortex in the 8-week DEP group compared with the control group. The levels of VGLUT1, VGLUT2, and VGAT were elevated in the cerebral cortex of the 8-week DEP group compared with the control group. In immunostaining of the temporal cortex, the expression of neurocan, VGLUT1, and GAD67 were increased in the 8-week DEP group compared with the control group. The 4-week DEP inhalation impaired spatial activities and olfactory sensitivities. After 8 weeks of DEP exposure, the PNN components and their proteolytic enzymes and the vesicular transporters increased in the cerebral cortex.
Effects of multiple N, P, and K fertilizer combinations on adzuki bean (Vigna angularis) yield in a semi-arid region of northeastern China
Authors: Yin Zhi-chao , Guo Wen-yun , Liang Jie , Xiao Huan-yu , Hao Xi-yu , Hou An-fu , Zong Xu-xiao , Leng Ting-rui , Wang Ying-jie , Wang Qing-yu , Yin Feng-xiang 
Published: December 2019

AbstractNitrogen (N), phosphorus (P), and potassium (K) exert various effects on adzuki bean yields. Our research was conducted in a semi-arid area, and four test sites were established in environments that have chernozem or sandy loam soils. During a five-year period, the effects of N, P, and K fertilizers on yield were comprehensively investigated in field trials (2014–2016) and for model-implementation trials (2017–2018), with models established prior to the latter. In the field trials, 23 treatments comprising different N, P, and K combinations significantly affected both yield and yield components, and regression analysis indicated that the experimental results were suitable for model establishment. The model subsequently demonstrated that the yield and the yield components were more sensitive to N and K fertilizer than to P fertilizer. Moreover, the yield and yield components increased. These yield increases were intense in response to the 0.5 to 1.34 levels in terms of the single effects; interaction effects; and the effects of combinations of N, P, and K fertilizers. Moreover, the effects of combinations of N, P, and K fertilizers were more significant on yield than were the single or interaction effects of N, P, and K fertilizers. The optimal fertilizer combination that resulted in high yields (≥1941.53 kg ha−1) comprised 57.23–68.43 kg ha−1 N, 36.04–47.32 kg ha−1 P2O5 and 50.29–61.27 kg ha−1 K2O. The fertilizer combination that resulted in the maximum yield was 62.98 kg ha−1 N, 47.04 kg ha−1 P2O5 and 59.95 kg ha−1 K2O (N:P2O5:K2O = 1:0.75:0.95), which produced the model-expected yield in trials at multiple sites. An economical fertilizer combination was determined on the basis of the best fertilizer measures in consideration of the cost of fertilizer and seed; this combination achieved yields of 2236.17 kg ha−1, the profit was 15,653.16 Yuan ha−1, and the corresponding rates were 57.60 kg ha−1 N, 47.03 kg ha−1 P2O5, and 31.64 kg ha−1 K2O (N:P2O5:K2O = 1:0.82:0.55).
Identification of a novel cholesterol-lowering dipeptide, phenylalanine-proline (FP), and its down-regulation of intestinal ABCA1 in hypercholesterolemic rats and Caco-2 cells
Authors: Banno Arata , Wang Jilite , Okada Kenji , Mori Ryosuke , Mijiti Maihemuti , Nagaoka Satoshi 
Published: December 2019

AbstractThere has been no report about in vivo active cholesterol-lowering dipeptide in any protein origin, despite their potential health benefits. Cattle heart protein hydrolysate ultra-filtrate (HPHU, molecular weight < ca. 1,000 Da peptide mixture) exhibits cholesterol-lowering activity in hypercholesterolemic rats, but the active peptide in HPHU that lowers serum cholesterol levels and its molecular mechanism are unknown. In this study, we separated and purified HPHU to identify a novel cholesterol-lowering dipeptide (phenylalanine-proline, FP) and characterized the mechanism underlying its effects in vivo and in vitro. We identified FP as an active peptide from HPHU by MALDI-TOF mass spectrometry. FP significantly decreased serum total and non-HDL cholesterol and hepatic cholesterol levels in rats. FP significantly increased serum HDL cholesterol, accompanied by a significant decrease in the atherogenic index. FP also significantly increased fecal cholesterol and acidic steroid excretion. Moreover, FP significantly decreased ATP-binding cassette transporter A1 (ABCA1) expression in the rat jejunum and reduced cholesterol absorption in Caco-2 cells. We found a novel cholesterol-lowering dipeptide FP that could improve cholesterol metabolism via the down-regulation of intestinal ABCA1. The cholesterol-lowering action induced by FP was disappeared in PepT1KO mice. FP-induced cholesterol-lowering action is mediated via PepT1 in mice.
Nanoparticle-Biological Interactions in a Marine Benthic Foraminifer
Authors: Ciacci Caterina , Grimmelpont Margot V. , Corsi Ilaria , Bergami Elisa , Curzi Davide , Burini Debora , Bouchet Vincent M. P. , Ambrogini Patrizia , Gobbi Pietro , Ujiié Yurika , Ishitani Yoshiyuki , Coccioni Rodolfo , Bernhard Joan M. , Frontalini Fabrizio 
Published: December 2019

AbstractThe adverse effects of engineered nanomaterials (ENM) in marine environments have recently attracted great attention although their effects on marine benthic organisms such as foraminifera are still largely overlooked. Here we document the effects of three negatively charged ENM, different in size and composition, titanium dioxide (TiO2), polystyrene (PS) and silicon dioxide (SiO2), on a microbial eukaryote (the benthic foraminifera Ammonia parkinsoniana) using multiple approaches. This research clearly shows the presence, within the foraminiferal cytoplasm, of metallic (Ti) and organic (PS) ENM that promote physiological stress. Specifically, marked increases in the accumulation of neutral lipids and enhanced reactive oxygen species production occurred in ENM-treated specimens regardless of ENM type. This study indicates that ENM represent ecotoxicological risks for this microbial eukaryote and presents a new model for the neglected marine benthos by which to assess natural exposure scenarios.
Investigating sex differences, cognitive effort, strategy, and performance on a computerised version of the mental rotations test via eye tracking
Authors: Toth Adam J. , Campbell Mark J. 
Published: December 2019

AbstractMental rotation tests (MRTs) have previously shown one of the most prominent sex differences in cognitive psychology, marked by a large male performance advantage. However, debate continues over the reasons for these sex differences. Previously, we used pupillometry to demonstrate sex differences in the cognitive effort invoked during the original MRT. Here, we evaluated the magnitude of sex differences during performance on a computerized version of the Vandenberg and Kuse MRT. Secondly, we examined whether fixation metrics could illuminate strategy use by participants. Finally, we used pupillometry to investigate whether cognitive effort differed between sexes and trials of different difficulty. While our results demonstrate no performance differences between sexes on the computerized MRT, fixation patterns provided evidence that gaze strategy was associated with performance on different parts of the test. Moreover, we show the cognitive demand of the V&K MRT, evidenced by large task dependent increases in participants’ pupil diameters.