bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction between NMDA Receptor- and Endocannabinoid-Mediated Modulation of Nociceptive Synapses
Authors: Yuan Sharleen , Burrell Brian D. 
Published: February 2019

AbstractNociceptors, sensory neurons that detect damage or potential damage to the body, are the first stage of communicating noxious stimuli from the periphery to central nervous system (CNS). In this study, long-term potentiation (LTP) in the CNS of the medicinal leech, Hirudo verbana, was examined, taking advantage of the ability to selectively record from nociceptive synapses in this model organism. High frequency stimulation (HFS) of nociceptors produced a persistent increase in synaptic transmission and this LTP was both NMDA receptor-mediated and synapse-specific. Surprisingly, inhibition of NMDA receptors during HFS “uncovered” a persistent form of depression. This long-term depression (LTD) was mediated by the endocannabinoid 2-arachidonoyl glycerol (2-AG) acting on a TRPV (transient receptor potential vanilloid) –like channel. These observations suggest that (1) NMDA receptor mediated LTP is observed in nociceptors across both vertebrate and invertebrate phyla and (2) there may be an interaction between NMDA receptor-mediated and endocannabinoid-mediated forms of synaptic plasticity in nociceptors. Specifically, the NMDA receptor mediated processes may suppress endocannabinoid signaling. Such findings could be significant for understanding cellular mechanisms behind nociceptive sensitization and perhaps their contribution to chronic pain.
Optimization of Pulmonary Vasculature Tridimensional Phenotyping in The Rat Fetus
Authors: Aydin Emrah , Levy Brittany , Oria Marc , Nachabe Hussam , Lim Foong-Yen , Peiro Jose L. 
Published: February 2019

AbstractComparative, functional, developmental, and some morphological studies on animal anatomy require accurate visualization of three-dimensional structures. Nowadays, several widely applicable methods exist for non-destructive whole-mount imaging of animal tissues. The purpose of this study was to optimize specimen preparation and develop a method for quantitative analysis of the total pulmonary vasculature in fetal rats. Tissues were harvested at E21 and fetuses fixed overnight in 4% paraformaldehyde/phosphate buffered saline. They were treated with 25% Lugol solution for 72 hours to ensure perfusion. Four different methods were used for fetal specimen preparation; isolated lung, upper torso, direct right ventricle contrast injection, and whole body with partial thoracic skin excision. The microCT scan was performed, and pulmonary vasculature was segmented. Vessels were analyzed for diameter, length, and branching. Of the four preparation methods, only whole body with partial thoracic skin excision resulted in adequate reconstruction of the pulmonary vasculature. In silico generated 3D images gathered by micro CT showed pulmonary vasculature distributed throughout the lung, which was representative of the shape and structure of the lungs. The mean number of vessels segmented in the pulmonary tree was 900 ± 24 with a mean diameter of 134.13 µm (range 40.72–265.69 µm). While up to the 30th generation of vessels could be segmented, both for arteries and veins, the majority of branching was between the 21st and 30th generations. Passive diffusion of contrast material enables quantitative analysis of the fetal pulmonary vasculature. This technique is a useful tool to analyze the characteristics and quantify the fetal pulmonary vasculature.
Encoding information into autonomously bursting neural network with pairs of time-delayed pulses
Authors: Kim June Hoan , Lee Ho Jun , Choi Wonshik , Lee Kyoung J. 
Published: February 2019

AbstractBiological neural networks with many plastic synaptic connections can store external input information in the map of synaptic weights as a form of unsupervised learning. However, the same neural network often produces dramatic reverberating events in which many neurons fire almost simultaneously – a phenomenon coined as ‘population burst.’ The autonomous bursting activity is a consequence of the delicate balance between recurrent excitation and self-inhibition; as such, any periodic sequences of burst-generating stimuli delivered even at a low frequency (~1 Hz) can easily suppress the entire network connectivity. Here we demonstrate that ‘Δt paired-pulse stimulation’, can be a novel way for encoding spatially-distributed high-frequency (~10 Hz) information into such a system without causing a complete suppression. The encoded memory can be probed simply by delivering multiple probing pulses and then estimating the precision of the arrival times of the subsequent evoked recurrent bursts.
Independent Left Ventricular Morphometric Atlases Show Consistent Relationships with Cardiovascular Risk Factors: A UK Biobank Study
Authors: Gilbert Kathleen , Bai Wenjia , Mauger Charlene , Medrano-Gracia Pau , Suinesiaputra Avan , Lee Aaron M. , Sanghvi Mihir M. , Aung Nay , Piechnik Stefan K. , Neubauer Stefan , Petersen Steffen E. , Rueckert Daniel , Young Alistair A. 
Published: February 2019

AbstractLeft ventricular (LV) mass and volume are important indicators of clinical and pre-clinical disease processes. However, much of the shape information present in modern imaging examinations is currently ignored. Morphometric atlases enable precise quantification of shape and function, but there has been no objective comparison of different atlases in the same cohort. We compared two independent LV atlases using MRI scans of 4547 UK Biobank participants: (i) a volume atlas derived by automatic non-rigid registration of image volumes to a common template, and (ii) a surface atlas derived from manually drawn epicardial and endocardial surface contours. The strength of associations between atlas principal components and cardiovascular risk factors (smoking, diabetes, high blood pressure, high cholesterol and angina) were quantified with logistic regression models and five-fold cross validation, using area under the ROC curve (AUC) and Akaike Information Criterion (AIC) metrics. Both atlases exhibited similar principal components, showed similar relationships with risk factors, and had stronger associations (higher AUC and lower AIC) than a reference model based on LV mass and volume, for all risk factors (DeLong p < 0.05). Morphometric variations associated with each risk factor could be quantified and visualized and were similar between atlases. UK Biobank LV shape atlases are robust to construction method and show stronger relationships with cardiovascular risk factors than mass and volume.
Comparison of different smartphone cameras to evaluate conjunctival hyperaemia in normal subjects
Authors: Otero Carles , García-Porta Nery , Tabernero Juan , Pardhan Shahina 
Published: February 2019

AbstractDespite the significant advantages that smartphones’ cameras can provide in teleophthalmology and artificial intelligence applications, their use as black-box systems for clinical data acquisition, without adequate information of the quality of photographs can compromise data accuracy. The aim of this study is to compare the objective and subjective quantification of conjunctival redness in images obtained with calibrated and non-calibrated cameras, in different lighting conditions and optical magnifications. One hundred ninety-two pictures of the eye were taken in 4 subjects using 3 smartphone cameras{Bq, Iphone, Nexus}, 2 lighting levels{high 815 lx, low 122 lx} and 2 magnification levels{high 10x, low 6x}. Images were duplicated: one set was white balanced and color corrected (calibrated) and the other was left as it was. Each image was subjective and objectively evaluated. There were no significant differences in subjective evaluation in any of the conditions whereas many statistically significant main effects and interaction effects were shown for all the objective metrics. The clinician’s evaluation was not affected by different cameras, lighting conditions or optical magnifications, demonstrating the effectiveness of the human eye’s color constancy properties. However, calibration of a smartphone’s camera is essential when extracting objective data from images.
Identification of Novel Regulatory Genes in APAP Induced Hepatocyte Toxicity by a Genome-Wide CRISPR-Cas9 Screen
Authors: Shortt Katherine , Heruth Daniel P. , Zhang NiNi , Wu Weibin , Singh Shipra , Li Ding-You , Zhang Li Qin , Wyckoff Gerald J. , Qi Lei S. , Friesen Craig A. , Ye Shui Qing 
Published: February 2019

AbstractAcetaminophen (APAP) is a commonly used analgesic responsible for more than half of acute liver failure cases. Identification of previously unknown genetic risk factors would provide mechanistic insights and novel therapeutic targets for APAP-induced liver injury. This study used a genome-wide CRISPR-Cas9 screen to evaluate genes that are protective against, or cause susceptibility to, APAP-induced liver injury. HuH7 human hepatocellular carcinoma cells containing CRISPR-Cas9 gene knockouts were treated with 15 mM APAP for 30 minutes to 4 days. A gene expression profile was developed based on the 1) top screening hits, 2) overlap of expression data from APAP overdose studies, and 3) predicted affected biological pathways. We further demonstrated the implementation of intermediate time points for the identification of early and late response genes. This study illustrated the power of a genome-wide CRISPR-Cas9 screen to systematically identify novel genes involved in APAP-induced hepatotoxicity and to provide potential targets to develop novel therapeutic modalities.
GPER activation protects against epithelial barrier disruption by Staphylococcus aureus α-toxin
Authors: Triplett Kathleen D. , Pokhrel Srijana , Castleman Moriah J. , Daly Seth M. , Elmore Bradley O. , Joyner Jason A. , Sharma Geetanjali , Herbert Guy , Campen Matthew J. , Hathaway Helen J. , Prossnitz Eric R. , Hall Pamela R. 
Published: February 2019

AbstractSex bias in innate defense against Staphylococcus aureus skin and soft tissue infection (SSTI) is dependent on both estrogen production by the host and S. aureus secretion of the virulence factor, α-hemolysin (Hla). The impact of estrogen signaling on the immune system is most often studied in terms of the nuclear estrogen receptors ERα and ERβ. However, the potential contribution of the G protein-coupled estrogen receptor (GPER) to innate defense against infectious disease, particularly with respect to skin infection, has not been addressed. Using a murine model of SSTI, we found that GPER activation with the highly selective agonist G-1 limits S. aureus SSTI and Hla-mediated pathogenesis, effects that were absent in GPER knockout mice. Specifically, G-1 reduced Hla-mediated skin lesion formation and pro-inflammatory cytokine production, while increasing bacterial clearance. In vitro, G-1 reduced surface expression of the Hla receptor, ADAM10, in a human keratinocyte cell line and increased resistance to Hla-mediated permeability barrier disruption. This novel role for GPER activation in skin innate defense against infectious disease suggests that G-1 may have clinical utility in patients with epithelial permeability barrier dysfunction or who are otherwise at increased risk of S. aureus infection, including those with atopic dermatitis or cancer.
Fatty acid profiles of muscle, liver, heart and kidney of Australian prime lambs fed different polyunsaturated fatty acids enriched pellets in a feedlot system
Authors: Van Le Hung , Nguyen Don Viet , Vu Nguyen Quang , Malau-Aduli Bunmi Sherifat , Nichols Peter David , Malau-Aduli Aduli Enoch Othniel 
Published: February 2019

AbstractWe investigated the effect of various dietary polyunsaturated fatty acid (PUFA) sources on the fatty acid profiles of muscle, liver, heart and kidney of Australian prime lambs. Seventy-two White Suffolk x Corriedale first-cross lambs weaned at 6 months of age were randomly allocated to the following six treatments: (1) Control: Lucerne hay only; wheat-based pellets infused with 50 ml/kg dry matter (DM) of oil from (2) rice bran (RBO); (3) canola (CO); (4) rumen-protected (RPO), (5) flaxseed (FSO) and (6) safflower (SO) sources in a completely randomized experimental design. Lambs in CO, FSO, SO and RPO treatments achieved contents of eicosapentaenoic acid (EPA, 22:5n-3) plus docosahexaenoic acid (DHA, 22:6n-3) in the longissimus dorsi muscle ranging from 31.1 to 57.1 mg/135 g, over and above the 30 mg per standard serve (135 g) threshold for “source” claim under the Australian guidelines. There was no difference in n-3 LC-PUFA contents in longissimus dorsi muscle of lambs fed dietary oils of plant origin. The highest 18:3n-3 (ALA) contents achieved with FSO diet in the muscle, liver and heart were 45.6, 128.1 and 51.3 mg/100 g, respectively. Liver and kidney contained high contents of n-3 LC-PUFA (ranging from 306.7 to 598.2 mg/100 g and 134.0 to 300.4 mg/100 g, respectively), with all values readily exceeding the ‘good source’ status (60 mg per serve under Australian guidelines). The liver and kidney of PUFA fed lambs can be labelled as ‘good source’ of n-3 LC-PUFA based on EPA and DHA contents stipulated by the Food Standards of Australia and New Zealand guidelines. Therefore, if lamb consumers consider eating the liver and kidney as their dietary protein sources, they can adequately obtain the associated health benefits of n-3 LC-PUFA.
Correlation of systemic arterial stiffness with changes in retinal and choroidal microvasculature in type 2 diabetes
Authors: Kim Mirinae , Kim Rae-Young , Kim Joo-Young , Park Young-Hoon 
Published: February 2019

AbstractThis study was conducted to assess whether systemic arterial stiffness, indicated by cardio-ankle vascular index (CAVI), is related to changes in the microvasculature of the retina and choroid in diabetes mellitus (DM). This study included 113 patients with a confirmed diagnosis of type-2 DM. Among them, 18 patients did not have diabetic retinopathy (DR), 71 had non-proliferative DR (NPDR), and 24 had proliferative DR (PDR). The mean CAVI was 7.58 ± 1.41 in no DR, 8.72 ± 1.47 in NPDR, and 8.43 ± 1.25 in PDR group. Of the 113 eyes, 42 (37.2%) were classified as abnormal CAVI group (CAVI ≥ 9). This group had significantly higher cardiac autonomic neuropathy risk index score, decreased central choroidal thickness, and decreased choroidal vascularity index (CVI). Deep foveal avascular zone area was higher in the abnormal CAVI group. After adjustment for possible confounding factors, CAVI showed negative correlation with the CVI (r = −0.247, P = 0.013). In conclusion, there was a significant correlation between arteriosclerosis and choroidal vascular changes in DR. We suggest prompt ophthalmic evaluation in patients with systemic arteriosclerosis. If the ophthalmologist notes advanced DR, the patient should be referred to a cardiovascular clinic for detailed evaluation of systemic arteriosclerosis.
Patterns of cardiovascular variability after long-term sino-aortic denervation in unanesthetized adult rats
Authors: Radaelli Alberto , Mancia Giuseppe , De Carlini Caterina , Soriano Francesco , Castiglioni Paolo 
Published: February 2019

AbstractBaroreflex dysfunction is a diffuse chronic condition that is expected to be followed by a profound loss of organization of BP and HR variability. Nevertheless, long-term effects of baroreflex withdrawal are still debated. Aim of our work was to study BP and HR changes long term after sino-aortic denervation (SAD). Inter-beat-interval (IBI) and intra-arterial BP were recorded beat-by-beat in 43 Wistar-Kyoto rats (Controls, n = 33; SAD rats, n = 10). Power spectra were calculated in controls and in SAD rats within three days and at seven months from denervation. Compared to controls, chronic SAD rats showed 1) similar mean BP (control vs SAD: 95 ± 16 vs 87 ± 22 mmHg) and IBI (171 ± 22 vs 181 ± 15 ms) values, 2) dramatically higher values of BP variance (12 ± 2 vs 64 ± 2 mmHg2, p < 0.01) and of ultra- (ULF) and very-low-frequency (VLF) BP oscillations, 3) dramatically higher values of IBI variability (24 ± 2 vs 71 ± 4 ms2, p < 0.01) and of ULF-IBI oscillations that were synchronized with BP oscillations. Chronic SAD rats reveal a marked change in the pattern of cardiovascular variability characterized by the appearance of synchronized slower oscillations of BP and HR. The cardiovascular system, therefore, retains a high level of organization despite the absence of a reflex control mechanism.
Mean diffusivity related to collectivism among university students in Japan
Authors: Nakagawa Seishu , Takeuchi Hikaru , Taki Yasuyuki , Nouchi Rui , Kotozaki Yuka , Shinada Takamitsu , Maruyama Tsukasa , Sekiguchi Atsushi , Iizuka Kunio , Yokoyama Ryoichi , Yamamoto Yuki , Hanawa Sugiko , Araki Tsuyoshi , Miyauchi Carlos Makoto , Magistro Daniele , Sakaki Kohei , Jeong Hyeonjeong , Sasaki Yukako , Kawashima Ryuta 
Published: February 2019

AbstractCollectivism is an important factor for coping with stress in one’s social life. To date, no imaging studies have revealed a direct association between collectivism and white matter structure. Collectivism is positively related to independence, harm avoidance, rejection sensitivity, cooperativeness, external locus of control, and self-monitoring and negatively related to need for uniqueness. Accordingly, we hypothesised that the neural structures underpinning collectivism are those that are also involved with its relationship using magnetic resonance imaging (MRI). This study aimed to identify the brain structures associated with collectivism in healthy young adults (n = 797), using regional grey and white matter volume, fractional anisotropy, and mean diffusivity (MD) analyses of MRI data. Scores on the collectivism scale were positively associated with MD values in the bilateral dorsolateral prefrontal cortex, left orbitofrontal cortex, inferior frontal gyrus, right superior temporal gyrus, ventral posterior cingulate cortex, globus pallidus, and calcarine cortex using the threshold-free cluster enhancement method with family-wise errors corrected to P < 0.05 at the whole-brain level. No significant associations between were found collectivism and other measures. Thus, the present findings supported our hypothesis that the neural correlates of collectivism are situated in regions involved in its related factors.
Dietary Niacin Intake Predicts the Decrease of Liver Fat Content During a Lifestyle Intervention
Authors: Linder Katarzyna , Willmann Caroline , Kantartzis Konstantinos , Machann Jürgen , Schick Fritz , Graf Marjo , Kümmerle Sabine , Häring Hans-Ulrich , Fritsche Andreas , Stefan Norbert , Wagner Róbert 
Published: February 2019

AbstractNiacin inhibits fatty acid flux from adipose tissue to liver, reduces hepatic triglyceride synthesis and increases hepatic lipid oxidation. Thus, niacin may have a role in the regulation of liver fat content in humans. We tested if dietary intake of niacin predicts change of liver fat content during a lifestyle intervention. To this end, we estimated the composition of diet from diaries of 202 healthy subjects at risk of type 2 diabetes undergoing lifestyle intervention comprising physical activity and diet counselling. Total-, subcutaneous- and visceral adipose tissue mass were measured by magnetic resonance (MR) tomography and liver fat content by 1H-MR spectroscopy at baseline and after 9 months of follow-up. Among fat compartments, liver fat content showed the largest decrease (−32%, p < 0.0001). High baseline niacin intake predicted a larger decrease of liver fat (p = 0.004). Subjects in the highest quartile of niacin intake at baseline also had the largest decrease of liver fat (1st:−10%; 2nd:−27%; 3rd:−35%; 4th:−37%). Among 58 subjects with nonalcoholic fatty liver disease (NAFLD) at baseline, NAFLD resolved in 23 subjects during the lifestyle intervention. For one standard deviation increase in niacin intake, the odds ratio for resolution of NAFLD was 1.77 (95% CI, 1.00–3.43). High dietary niacin intake may have a favorable effect on the reduction of liver fat during lifestyle intervention.
Metformin enhances the radiosensitizing effect of cisplatin in non-small cell lung cancer cell lines with different cisplatin sensitivities
Authors: Riaz Muhammad Assad , Sak Ali , Erol Yasin Bahadir , Groneberg Michael , Thomale Jürgen , Stuschke Martin 
Published: February 2019

AbstractCisplatin is an extensively used chemotherapeutic drug for lung cancer, but the development of resistance decreases its effectiveness in the treatments of non-small cell lung cancer (NSCLC). In this study, we examined the effects of metformin, a widely used antidiabetic drug, on cisplatin radiosensitization in NSCLC cell lines. Human NSCLC cell lines, A549 (cisplatin-resistant) and H460 (cisplatin-sensitive), were treated with metformin, cisplatin or a combination of both drugs before ionizing radiation. Cell proliferation, clonogenic assays, western blotting, cisplatin-DNA adduct formation and immunocytochemistry were used to characterize the treatments effects. Metformin increased the radiosensitivity of NSCLC cells. Metformin showed additive and over-additive effects in combination with cisplatin and the radiation response in the clonogenic assay in H460 and A549 cell lines (p = 0.018 for the interaction effect between cisplatin and metformin), respectively. At the molecular level, metformin led to a significant increase in cisplatin-DNA adduct formation compared with cisplatin alone (p < 0.01, ANOVA-F test). This was accompanied by a decreased expression of the excision repair cross-complementation 1 expression (ERCC1), a key enzyme in nucleotide excision repair pathway. Furthermore, compared with each treatment alone metformin in combination with cisplatin yielded the lowest level of radiation-induced Rad51 foci, an essential protein of homologous recombination repair. Ionizing radiation-induced γ-H2AX and 53BP1 foci persisted longer in both cell lines in the presence of metformin. Pharmacological inhibition of AMP-activated protein kinase (AMPK) demonstrated that metformin enhances the radiosensitizing effect of cisplatin through an AMPK-dependent pathway only in H460 but not in A549 cells. Our results suggest that metformin can enhance the effect of combined cisplatin and radiotherapy in NSCLC and can sensitize these cells to radiation that are not sensitized by cisplatin alone.
Environmental stresses suppress nonsense-mediated mRNA decay (NMD) and affect cells by stabilizing NMD-targeted gene expression
Authors: Usuki Fusako , Yamashita Akio , Fujimura Masatake 
Published: February 2019

AbstractNonsense-mediated mRNA decay (NMD) is a cellular mechanism that eliminates mRNAs that harbor premature translation termination codons (PTCs). Here, we investigated the effects of environmental stresses (oxidative stress and endoplasmic reticulum (ER) stress) on NMD activity. Methylmercury (MeHg) was used to cause oxidative stress and thapsigargin to stress the ER. NMD suppression, evidenced by upregulation of NMD-sensitive mRNAs and a decrease in UPF1 phosphorylation, was observed in MeHg-treated myogenic cells, cerebral cortical neuronal cells, and astroglial cells. Mild ER stress amplified NMD suppression caused by MeHg. To elucidate the cause of stress-induced NMD suppression, the role of the phospho-eIF2α/ATF4 pathway was investigated. Knockdown and non-phosphorylatable eIF2α-transfection studies demonstrated the critical role of phospho-eIF2α-mediated repression of translation in mild ER stress-induced NMD suppression. However, NMD suppression was also observed in phospho-eIF2α-deficient cells under mild ER stress. Mechanistic target of rapamycin suppression-induced inhibition of cap-dependent translation, and downregulation of the NMD components UPF1, SMG7, and eIF4A3, were probably involved in stress-induced NMD suppression. Our results indicate that stress-induced NMD suppression has the potential to affect the condition of cells and phenotypes of PTC-related diseases under environmental stresses by stabilizing NMD-targeted gene expression.