bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endogenous arginase 2 as a potential biomarker for PEGylated arginase 1 treatment in xenograft models of squamous cell lung carcinoma
Authors: Lam Sze-Kwan , Yan Sheng , Xu Shi , U Kin-Pong , Cheng Paul Ning-Man , Ho James Chung-Man 
Published: February 2019

AbstractDepletion of arginine induced by PEGylated arginase 1 (ARG1) (BCT-100) has shown anticancer effects in arginine auxotrophic cancers that lack argininosuccinate synthetase (ASS1) and ornithine transcarbamylase (OTC). High levels of endogenous arginase 2 (ARG2) have been previously reported in human lung cancers. Although a high-ARG2 level neither causes immunosuppression nor affects disease progression, it may theoretically affect the efficacy of PEGylated ARG1 treatment. ARG2 was shown to be highly expressed in H520 squamous cell lung carcinoma (lung SCC) xenografts but undetectable in SK-MES-1 and SW900 lung SCC xenografts. We propose that high-endogenous expression of ARG2 could impede the anti-tumor effect of PEGylated ARG1 in lung SCC. The in vivo effect of PEGylated ARG1 was investigated using three xenograft models of lung SCC. PEGylated ARG1 (60 mg/kg) suppressed tumor growth in SK-MES-1 and SW900 but not H520 xenografts. ASS1 was expressed in SK-MES-1 and SW900 xenografts while OTC expression remained low in all xenografts. A high-endogenous ARG2 level was detected only in H520 xenografts. Serum arginine level was decreased significantly by PEGylated ARG1 in all xenografts. Nonetheless intratumoral arginine level was decreased by PEGylated ARG1 in SK-MES-1 and SW900, not H520 xenografts. In SK-MES-1 xenografts, PEGylated ARG1 treatment induced G1 arrest, downregulation of Ki67 and Mcl-1 and activation of apoptosis. In SW900 xenografts, upregulation of Bim and activation of apoptosis were observed upon PEGylated ARG1 treatment. Silencing of ARG2 re-sensitized the H520 xenografts to PEGylated ARG1 treatment, partially mediated through arginine depletion via G1 arrest and apoptosis. PEGylated ARG1 treatment (BCT-100) was effective in lung SCC xenografts with low-endogenous levels of ASS1/OTC and ARG2. High-endogenous ARG2 expression may cause resistance to PEGylated ARG1 treatment in lung SCC xenografts. ARG2 may serve as a third predictive biomarker in PEGylated ARG1 treatment in lung SCC.
Management of cardiovascular risk in patients with multiple myeloma
Authors: Plummer Chris , Driessen Christoph , Szabo Zsolt , Mateos María-Victoria 
Published: February 2019

AbstractMultiple myeloma (MM) is a plasma cell malignancy that accounts for 10% of hematological cancers. It predominantly affects elderly people; median age at diagnosis is 70 years. Consequently, many patients with MM have cardiovascular comorbidities or risk factors. MM can cause cardiac comorbidities such as cardiomyopathy and heart failure caused by cardiac amyloidosis and/or anemia. Some of the treatments used in MM can also affect cardiovascular health. Advances in pharmacotherapy for MM, such as the introduction of immunomodulators, proteasome inhibitors, histone deacetylase inhibitors, and monoclonal antibodies, have dramatically improved progression-free survival and life expectancy, but new agent classes are associated with adverse events that were not previously observed on a regular basis, including cardiovascular events. However, with careful risk assessment, monitoring, and prophylactic therapy, many of these cardiovascular complications can be managed or treated successfully. Most routine cardiovascular surveillance is undertaken by the treating hemato-oncologist, but a multidisciplinary approach involving cardiologists may help to optimize patient outcomes. In this review, we survey the cardiac complications commonly reported in patients with MM, discuss how they can be prevented and managed, and summarize the role cardiologists can play in delivering the best possible outcomes for patients with MM and cardiovascular comorbidities.
A snapshot of biodiversity protection in Antarctica
Authors: Wauchope Hannah S. , Shaw Justine D. , Terauds Aleks 
Published: February 2019

AbstractThreats to Antarctic biodiversity are escalating, despite its remoteness and protection under the Antarctic Treaty. Increasing human activity, pollution, biological invasions and the omnipresent impacts of climate change all contribute, and often combine, to exert pressure on Antarctic ecosystems and environments. Here we present a continent-wide assessment of terrestrial biodiversity protection in Antarctica. Despite Antarctic Specially Protected Areas covering less than 2% of Antarctica, 44% of species (including seabirds, plants, lichens and invertebrates) are found in one or more protected areas. However, protection is regionally uneven and biased towards easily detectable and charismatic species like seabirds. Systematic processes to prioritize area protection using the best available data will maximize the likelihood of ensuring long-term protection and conservation of Antarctic biodiversity.
Validation of vessel size imaging (VSI) in high-grade human gliomas using magnetic resonance imaging, image-guided biopsies, and quantitative immunohistochemistry
Authors: Chakhoyan Ararat , Yao Jingwen , Leu Kevin , Pope Whitney B. , Salamon Noriko , Yong William , Lai Albert , Nghiemphu Phioanh L. , Everson Richard G. , Prins Robert M. , Liau Linda M. , Nathanson David A. , Cloughesy Timothy F. , Ellingson Benjamin M. 
Published: February 2019

AbstractTo evaluate the association between a vessel size index (VSIMRI) derived from dynamic susceptibility contrast (DSC) perfusion imaging using a custom spin-and-gradient echo echoplanar imaging (SAGE-EPI) sequence and quantitative estimates of vessel morphometry based on immunohistochemistry from image-guided biopsy samples. The current study evaluated both relative cerebral blood volume (rCBV) and VSIMRI in eleven patients with high-grade glioma (7 WHO grade III and 4 WHO grade IV). Following 26 MRI-guided glioma biopsies in these 11 patients, we evaluated tissue morphometry, including vessel density and average radius, using an automated procedure based on the endothelial cell marker CD31 to highlight tumor vasculature. Measures of rCBV and VSIMRI were then compared to histological measures. We demonstrate good agreement between VSI measured by MRI and histology; VSIMRI = 13.67 μm and VSIHistology = 12.60 μm, with slight overestimation of VSIMRI in grade III patients compared to histology. rCBV showed a moderate but significant correlation with vessel density (r = 0.42, p = 0.03), and a correlation was also observed between VSIMRI and VSIHistology (r = 0.49, p = 0.01). The current study supports the hypothesis that vessel size measures using MRI accurately reflect vessel caliber within high-grade gliomas, while traditional measures of rCBV are correlated with vessel density and not vessel caliber.
Natural enamel caries, dentine reactions, dentinal fluid and biofilm
Authors: de Barros Pinto Laryssa , Lira Maria Luiza Lima Alves , Cavalcanti Yuri Wanderley , Dantas Eugênia Livia de Andrade , Vieira Maria Lúcia Oliveira , de Carvalho Gabriel Garcia , de Sousa Frederico Barbosa 
Published: February 2019

AbstractIt is believed that penetration of dentinal fluid into natural enamel caries (NEC) is negligible because of the barrier created by underlying sclerotic dentine, but there are conflicting evidences on whether dentine subjacent to NEC is sclerotic or demineralized. This study aimed at investigating the relationship between NEC, subjacent dentine reactions, modification of dentinal fluid, and composition of cariogenic biofilm formed on the NEC surface. Proximal NEC (PNEC) lesions of human permanent posterior teeth were included in five experiments. Histologically, microradiographic analysis with contrast solution (MRC) in dentine revealed a decreased proportion of sclerotic dentine and an increased proportion of deep dentine demineralization compared to the classical stereomicroscopic histological analysis based on dentin color and translucency. Real-time MRC and 3D optical profilometry, and 3D microtomographic analysis evidenced a facilitated transport of modified dentinal fluid towards PNEC lesions. Cariogenic biofilm formed in vitro on the PNEC surface presented lower amounts of insoluble and soluble matrix polysaccharides when 2% chlorexidine was inserted in the pulp chamber. In conclusion, this study evidenced that dentine subjacent to PNEC is mostly demineralized, providing facilitated pathway for dentinal fluid to penetrate into PNEC and alter the composition of the biofilm formed on the PNEC surface.
Hyperactivation of mTORC1 disrupts cellular homeostasis in cerebellar Purkinje cells
Authors: Sakai Yusuke , Kassai Hidetoshi , Nakayama Hisako , Fukaya Masahiro , Maeda Tatsuya , Nakao Kazuki , Hashimoto Kouichi , Sakagami Hiroyuki , Kano Masanobu , Aiba Atsu 
Published: February 2019

AbstractMammalian target of rapamycin (mTOR) is a central regulator of cellular metabolism. The importance of mTORC1 signaling in neuronal development and functions has been highlighted by its strong relationship with many neurological and neuropsychiatric diseases. Previous studies demonstrated that hyperactivation of mTORC1 in forebrain recapitulates tuberous sclerosis and neurodegeneration. In the mouse cerebellum, Purkinje cell-specific knockout of Tsc1/2 has been implicated in autistic-like behaviors. However, since TSC1/2 activity does not always correlate with clinical manifestations as evident in some cases of tuberous sclerosis, the intriguing possibility is raised that phenotypes observed in Tsc1/2 knockout mice cannot be attributable solely to mTORC1 hyperactivation. Here we generated transgenic mice in which mTORC1 signaling is directly hyperactivated in Purkinje cells. The transgenic mice exhibited impaired synapse elimination of climbing fibers and motor discoordination without affecting social behaviors. Furthermore, mTORC1 hyperactivation induced prominent apoptosis of Purkinje cells, accompanied with dysregulated cellular homeostasis including cell enlargement, increased mitochondrial respiratory activity, and activation of pseudohypoxic response. These findings suggest the different contributions between hyperactivated mTORC1 and Tsc1/2 knockout in social behaviors, and reveal the perturbations of cellular homeostasis by hyperactivated mTORC1 as possible underlying mechanisms of neuronal dysfunctions and death in tuberous sclerosis and neurodegenerative diseases.
Recording single- and multi-unit neuronal action potentials from the surface of the dorsal root ganglion
Authors: Kashkoush Ahmed I. , Gaunt Robert A. , Fisher Lee E. , Bruns Tim M. , Weber Douglas J. 
Published: February 2019

AbstractThe dorsal root ganglia (DRG) contain cell bodies of primary afferent neurons, which are frequently studied by recording extracellularly with penetrating microelectrodes inserted into the DRG. We aimed to isolate single- and multi-unit activity from primary afferents in the lumbar DRG using non-penetrating electrode arrays and to characterize the relationship of that activity with limb position and movement. The left sixth and seventh lumbar DRG (L6-L7) were instrumented with penetrating and non-penetrating electrode arrays to record neural activity during passive hindlimb movement in 7 anesthetized cats. We found that the non-penetrating arrays could record both multi-unit and well-isolated single-unit activity from the surface of the DRG, although with smaller signal to noise ratios (SNRs) compared to penetrating electrodes. Across all recorded units, the median SNR was 1.1 for non-penetrating electrodes and 1.6 for penetrating electrodes. Although the non-penetrating arrays were not anchored to the DRG or surrounding tissues, the spike amplitudes did not change (<1% change from baseline spike amplitude) when the limb was moved passively over a limited range of motion (~20 degrees at the hip). Units of various sensory fiber types were recorded, with 20% of units identified as primary muscle spindles, 37% as secondary muscle spindles, and 24% as cutaneous afferents. Our study suggests that non-penetrating electrode arrays can record modulated single- and multi-unit neural activity of various sensory fiber types from the DRG surface.
Defining Optimal Soybean Sowing Dates across the US
Authors: Mourtzinis Spyridon , Specht James E. , Conley Shawn P. 
Published: February 2019

AbstractGlobal crop demand is expected to increase by 60–110% by 2050. Climate change has already affected crop yields in some countries, and these effects are expected to continue. Identification of weather-related yield-limiting conditions and development of strategies for agricultural adaptation to climate change is essential to mitigate food security concerns. Here we used machine learning on US soybean yield data, collected from cultivar trials conducted in 27 states from 2007 to 2016, to examine crop sensitivity to varying in-season weather conditions. We identified the month-specific negative effect of drought via increased water vapor pressure deficit. Excluding Texas and Mississippi, where later sowing increased yield, sowing 12 days earlier than what was practiced during this decade across the US would have resulted in 10% greater total yield and a cumulative monetary gain of ca. US$9 billion. Our data show the substantial nation- and region-specific yield and monetary effects of adjusting sowing timing and highlight the importance of continuously quantifying and adapting to climate change. The magnitude of impact estimated in our study suggest that policy makers (e.g., federal crop insurance) and laggards (farmers that are slow to adopt) that fail to acknowledge and adapt to climate change will impact the national food security and economy of the US.
G6Pase location in the endoplasmic reticulum: Implications on compartmental analysis of FDG uptake in cancer cells
Authors: Scussolini Mara , Bauckneht Matteo , Cossu Vanessa , Bruno Silvia , Orengo Anna Maria , Piccioli Patrizia , Capitanio Selene , Yosifov Nikola , Ravera Silvia , Morbelli Silvia , Piana Michele , Sambuceti Gianmario , Caviglia Giacomo , Marini Cecilia 
Published: February 2019

AbstractThe favourable kinetics of 18F-fluoro-2-deoxyglucose (FDG) permits to depict cancer glucose consumption by a single evaluation of late tracer uptake. This standard procedure relies on the slow radioactivity loss, usually attributed to the limited tumour expression of G6P-phosphatase (G6Pase). However, this classical interpretation intrinsically represents an approximation since, as in all tissues, cancer G6Pase activity is remarkable and is confined to the endoplasmic reticulum (ER), whose lumen must be reached by phosphorylated FDG to explain its hydrolysis and radioactivity release. The present study tested the impact of G6Pase sequestration on the mathematical description of FDG trafficking and handling in cultured cancer cells. Our data show that accounting for tracer access to the ER configures this compartment as the preferential site of FDG accumulation. This is confirmed by the reticular localization of fluorescent FDG analogues. Remarkably enough, reticular accumulation rate of FDG is dependent upon extracellular glucose availability, thus configuring the same ER as a significant determinant of cancer glucose metabolism.
New risk prediction model of coronary heart disease in participants with and without diabetes: Assessments of the Framingham risk and Suita scores in 3-year longitudinal database in a Japanese population
Authors: Hirai Hiroyuki , Asahi Koichi , Yamaguchi Satoshi , Mori Hirotaka , Satoh Hiroaki , Iseki Kunitoshi , Moriyama Toshiki , Yamagata Kunihiro , Tsuruya Kazuhiko , Fujimoto Shouichi , Narita Ichiei , Konta Tsuneo , Kondo Masahide , Shibagaki Yugo , Kasahara Masato , Watanabe Tsuyoshi , Shimabukuro Michio 
Published: February 2019

AbstractThe Framingham Risk Score (FRS) has been reported to predict coronary heart disease (CHD), but its assessment has been unsuccessful in Asian population. We aimed to assess FRS and Suita score (a Japanese CHD prediction model) in a Japanese nation-wide annual health check program, participants aged 40–79 years were followed up longitudinally from 2008 to 2011. Of 35,379 participants analyzed, 1,234 had new-onset CHD. New-onset CHD was observed in diabetic men [6.00%], non-diabetic men [3.96%], diabetic women [5.51%], and non-diabetic women [2.86%], respectively. Area under the curve (AUC) of receiver operating characteristic (ROC) curve for CHD prediction were consistently low in Suita score (TC), FRS (TC) and NCEP-ATPIII FRS (TC), suggesting that these scores have only a limited power. ROC, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA) and Hosmer–Lemeshow goodness-of-fit test did not show clear differences between Suita score (TC) and FRS (TC). New models combining waist circumference ≥85 cm in men or proteinuria ≥1+ in women to Suita score (TC) was superior in diabetic men and women. New models could be useful to predict 3-year risk of CHD at least in Japanese population especially in diabetic population.
Constructing Supported Cell Membranes with Controllable Orientation
Authors: Lyu Shao-Wei , Wang Jou-Fang , Chao Ling 
Published: February 2019

AbstractMembrane proteins play important roles in various cellular processes. Methods that can retain their structure and membrane topology information during their characterization are desirable for understanding their structure-function behavior. Here, we use giant plasma membrane vesicles (GPMVs) to form the supported cell membrane and develop a blotting method to control the orientation of the deposited cell membrane in order to study membrane proteins from either the extracellular or the cytoplasmic sides. We show that the membrane orientation can be retained in the directly-deposited membrane and the deposited membrane on mica can be blotted onto glass to reverse the membrane orientation. We used Aquaporin 3 (AQP3), an abundant native transmembrane protein in Hela cells, as a target to examine the cell membrane orientation in the directly-deposited and reversed membrane platforms. The immunostaining of antibodies targeting either the cyto-domain or ecto-domain of AQP3 shows that the intracellular side of the cell membrane faced the bulk aqueous environment when the GPMVs spontaneously ruptured on the support and that the membrane orientation was reversed after blotting. With this blotting method, we can thus control the orientation of the supported cell membrane to study membrane protein functions and structures from either side of the cell plasma membrane.
Behçet’s disease and genetic interactions between HLA-B*51 and variants in genes of autoinflammatory syndromes
Authors: Burillo-Sanz Sergio , Montes-Cano Marco-Antonio , García-Lozano José-Raúl , Olivas-Martínez Israel , Ortego-Centeno Norberto , García-Hernández Francisco-José , Espinosa Gerard , Graña-Gil Genaro , Sánchez-Bursón Juan , Juliá María Rosa , Solans Roser , Blanco Ricardo , Barnosi-Marín Ana-Celia , Gómez de la Torre Ricardo , Fanlo Patricia , Rodríguez-Carballeira Mónica , Rodríguez-Rodríguez Luis , Camps Teresa , Castañeda Santos , Alegre-Sancho Juan-Jose , Martín Javier , González-Escribano María Francisca 
Published: February 2019

AbstractBehçet’s disease (BD) is an immune-mediated systemic disorder with a well-established genetic base. In a previous study, using a next generation sequencing approach, we found many rare variants and some functional polymorphisms in genes related to autoinflammatory syndromes (AID): CECR1, MEFV, MVK, NLRP3, NOD2, PSTPIP1 and TNFRSF1A in our BD cohort. Our strategy did not allow us to establish either number of patients with variants, proportion of individuals accumulating them or relationship with other genetic factors. With the goal to answer these questions, the individual samples were sequenced. Additionally, three functional polymorphisms: NLRP3 p.Gln703Lys, NOD2 p.Arg702Trp and p.Val955Ile were genotyped using TaqMan assays. A total of 98 patients (27.6%) carried at least one rare variant and 13 of them (3.7%) accumulated two or three. Functional regression model analysis suggests epistatic interaction between B51 and MEFV (P = 0.003). A suggestive protective association of the minor allele of NOD2 p.Arg702Trp (P = 0.01) was found in both, B51 positive and negative individuals. Therefore, a high percentage of patients with BD have rare variants in AID genes. Our results suggest that the association of MEFV with BD could be modulated by the HLA molecules; whereas the protective effect of NOD2 p.Arg702Trp would be independent of HLA.
Distributions of soil branched glycerol dialkyl glycerol tetraethers from different climate regions of China
Authors: Wang M. , Zheng Z. , Zong Y. , Man M. , Tian L. 
Published: February 2019

AbstractDistributions of branched glycerol dialkyl glycerol tetraethers (brGDGTs) from soil bacteria have been recently used for reconstructions of past soil pH and air temperature history. Here, we report the brGDGTs distribution patterns from different climate regions of China, using 42 novel brGDGT data from sub-tropical Chinese soils, compiled alongside previously-published data encompassing different environmental conditions across China. These patterns show high abundance of Ia fraction in soils from humid areas, and high abundance of IIa′ and IIIa′ fractions corresponds to semi-humid or semi-arid conditions, implying a possible relationship with precipitation. The abundance of IIa fraction appears negatively correlated with air temperature. Statistically, the soil pH and temperature factors represent 62% and 30% variations of the total variance respectively. For soils from humid and semi-humid regions, strong correlations between cyclization of branched tetraethers (CBT′) index and soil pH (R2 = 0.89) and between methylation of branched tetraethers (MBT′5ME) index and mean annual temperature (MAT)(R2 = 0.82) exist. When soils from semi-arid regions are included, the correlations become slightly stronger with pH and significantly weaker with MAT. Our study confirms the usefulness of soil brGDGTs distributions for Quaternary palaeo-climate reconstructions.
Personality traits influence contest outcome, and vice versa, in a territorial butterfly
Authors: Kaiser Aurélien , Merckx Thomas , Van Dyck Hans 
Published: February 2019

AbstractHolding a territory is often crucial in order to acquire key resources, including mating partners. However, few studies have investigated the role of animal personality in the context of territorial conflicts and how the contest outcome itself may influence personality traits. We studied personality in male Speckled wood butterflies, Pararge aegeria, before and after territorial contests for sunspot territories. Before interactions, boldness decreased with age, while activity and exploration were only influenced by ambient conditions. Neither age nor morphology did influence the probability to win contests, but winners were more active and more explorative than losers and, moreover, males that received a red wing mark were more likely to be winners. Butterflies that lost a contest showed pronounced behavioural changes. Mean boldness increased and its repeatability was disrupted, while no such change was detected in winners. The observed boldness increase in losers may be explained by a ‘desperado effect’, though its implication for successive contests remains unknown. Given that territoriality is expected to have important consequences for reproductive success, our results suggest that personality traits may indirectly contribute to individual fitness by influencing the ability to gain access to mate-location patches.