bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-21 regulates SOCS1 expression in autoreactive CD8+ T cells but is not required for acquisition of CTL activity in the islets of non-obese diabetic mice
Authors: Sutherland Andrew P. R. , Graham Kate L. , Papadimitriou Michelle , Jhala Gaurang , Trivedi Prerak , Catterall Tara , Fynch Stacey , Kay Thomas W. H. , Thomas Helen E. 
Published: October 2019

AbstractIn type 1 diabetes, maturation of activated autoreactive CD8+ T cells to fully armed effector cytotoxic T lymphocytes (CTL) occurs within the islet. At present the signals required for the maturation process are poorly defined. Cytokines could potentially provide the necessary “third signal” required to generate fully mature CTL capable of killing insulin-producing β-cells. To determine whether autoreactive CTL within islets respond to cytokines we generated non-obese diabetic (NOD) mice with a reporter for cytokine signalling. These mice express a reporter gene, hCD4, under the control of the endogenous regulatory elements for suppressor of cytokine signalling (SOCS)1, which is itself regulated by pro-inflammatory cytokines. In NOD mice, the hCD4 reporter was expressed in infiltrated islets and the expression level was positively correlated with the frequency of infiltrating CD45+ cells. SOCS1 reporter expression was induced in transferred β-cell-specific CD8+ 8.3T cells upon migration from pancreatic draining lymph nodes into islets. To determine which cytokines induced SOCS1 promoter activity in islets, we examined hCD4 reporter expression and CTL maturation in the absence of the cytokine receptors IFNAR1 or IL-21R. We show that IFNAR1 deficiency does not confer protection from diabetes in 8.3 TCR transgenic mice, nor is IFNAR1 signalling required for SOCS1 reporter upregulation or CTL maturation in islets. In contrast, IL-21R-deficient 8.3 mice have reduced diabetes incidence and reduced SOCS1 reporter activity in islet CTLs. However IL-21R deficiency did not affect islet CD8+ T cell proliferation or expression of granzyme B or IFNγ. Together these data indicate that autoreactive CD8+ T cells respond to IL-21 and not type I IFNs in the islets of NOD mice, but neither IFNAR1 nor IL-21R are required for islet intrinsic CTL maturation.
Predicting low-concentration effects of pesticides
Authors: Liess Matthias , Henz Sebastian , Knillmann Saskia 
Published: October 2019

AbstractWe present a model to identify the effects of low toxicant concentrations. Due to inadequate models, such effects have so far often been misinterpreted as random variability. Instead, a tri-phasic relationship describes the effects of a toxicant when a broad range of concentrations is assessed: i) at high concentrations where substantial mortality occurs (LC50), we confirmed the traditional sigmoidal response curve (ii) at low concentrations about 10 times below the LC50, we identified higher survival than previously modelled, and (iii) at ultra-low concentrations starting at around 100 times below the LC50, higher mortality than previously modelled. This suggests that individuals benefit from low toxicant stress. Accordingly, we postulate that in the absence of external toxicant stress individuals are affected by an internal “System Stress” (SyS) and that SyS is reduced with increasing strength of toxicant stress. We show that the observed tri-phasic concentration-effect relationship can be modelled on the basis of this approach. Here we revealed that toxicant-related effects (LC5) occurred at remarkably low concentrations, 3 to 4 orders of magnitude below those concentrations inducing strong effects (LC50). Thus, the ECx-SyS model presented allows us to attribute ultra-low toxicant concentrations to their effects on individuals. This information will contribute to performing a more realistic environmental and human risk assessment.
Differential effects of synthetic media on long-term growth, starch accumulation and transcription of ADP-glucosepyrophosphorylase subunit genes in Landoltia punctata
Authors: Kittiwongwattana Chokchai 
Published: October 2019

AbstractMurashige & Skoog (MS) and Hoagland’s media were previously used for in vitro culture of Landoltia punctata. During subsequent ex vitro culture, the use of MS medium resulted in a higher growth rate, compared to Hoagland’s medium. Thus, a higher starch content of L. punctata in MS medium was previously hypothesized. Here, L. punctata strain 5632 was isolated and characterized using morphological characteristics and the atpF-atpH intergenic region. During early cultivation stage, fresh weight and relative growth rate in MS medium were lower than Hoagland’s medium. Conversely, starch content in MS medium was considerably higher than in Hoagland’s medium. Medium effects on expression of genes coding for starch-biosynthesis ADP-glucosepyrophosphorylase (AGPase) were determined. Genomic fragments of small (LeAPS) and large (LeAPL1) AGPase subunits were characterized. Differential expression between each AGPase subunit genes was observed in both media. Additionally, in MS medium, the highest correlation coefficients between starch content and gene expression was found with LeAPS (0.81) and followed by LeAPL3 (0.67), LeAPL2 (0.65) and LeAPL1 (0.28). In Hoagland’s medium, the coefficients of LeAPL3 (0.83) and LeAPL2 (0.62) were higher than LeAPS (0.18) and LeAPL1 (−0.62). This suggested different levels of contributions of these genes in starch biosynthesis in both media.
Dependence of track etching kinetics on chemical reactivity around the ion path
Authors: Gorbunov S. A. , Rymzhanov R. A. , Volkov A. E. 
Published: October 2019

AbstractEtching kinetics of swift heavy ions (SHI) tracks in olivine is investigated in frame of experimentally verified numerical approach. The model takes into account variation of induced chemical reactivity of the material around the whole ion trajectory with the nanometric accuracy. This enables a quantitative description of wet chemical etching of SHI tracks of different lengths and orientations towards to the sample surface. It is demonstrated that two different modes of etching, governed by diffusion of etchant molecules and by their reaction with the material must be observed in experiments using techniques with different resolution thresholds. Applicability limits of the optical microscopy for detection of heavy ion parameters by measuring of the lengthwise etching rates of the ion track are discussed.
Thioredoxin-related transmembrane protein 2 (TMX2) regulates the Ran protein gradient and importin-β-dependent nuclear cargo transport
Authors: Oguro Ami , Imaoka Susumu 
Published: October 2019

AbstractTMX2 is a thioredoxin family protein, but its functions have not been clarified. To elucidate the function of TMX2, we explored TMX2-interacting proteins by LC-MS. As a result, importin-β, Ran GTPase (Ran), RanGAP, and RanBP2 were identified. Importin-β is an adaptor protein which imports cargoes from cytosol to the nucleus, and is exported into the cytosol by interaction with RanGTP. At the cytoplasmic nuclear pore, RanGAP and RanBP2 facilitate hydrolysis of RanGTP to RanGDP and the disassembly of the Ran-importin-β complex, which allows the recycling of importin-β and reentry of Ran into the nucleus. Despite its interaction of TMX2 with importin-β, we showed that TMX2 is not a transport cargo. We found that TMX2 localizes in the outer nuclear membrane with its N-terminus and C-terminus facing the cytoplasm, where it co-localizes with importin-β and Ran. Ran is predominantly distributed in the nucleus, but TMX2 knockdown disrupted the nucleocytoplasmic Ran gradient, and the cysteine 112 residue of Ran was important in its regulation by TMX2. In addition, knockdown of TMX2 suppressed importin-β-mediated transport of protein. These results suggest that TMX2 works as a regulator of protein nuclear transport, and that TMX2 facilitates the nucleocytoplasmic Ran cycle by interaction with nuclear pore proteins.
Resolving the Architecture and Early Evolution of a Forearc Basin (Georgia Basin, Canada) Using Detrital Zircon
Authors: Huang Chuqiao , Dashtgard Shahin E. , Kent Bryan A. P. , Gibson H. Daniel , Matthews William A. 
Published: October 2019

AbstractConvergent-margin basins (CMBs) are commonly associated with active arcs, and hence are rich in detrital zircon (DZ) whose ages closely reflect the timing of deposition. Consequently, maximum depositional ages (MDA) from DZ geochronology can be employed to resolve the stratigraphy and evolution of CMBs. Herein, we use DZ to revise the internal architecture of the lower Nanaimo Group, which partially comprises the fill of the (forearc) Georgia (or Nanaimo) Basin. Maximum depositional ages and multi-dimensional scaling of DZ age distributions are employed to determine chronologic equivalency of strata and assess sediment provenance variability within the pre-existing lithostratigraphic framework. The results are compared to a recently developed sequence stratigraphic framework for the lower Nanaimo Group. The basal lithostratigraphic unit of the Nanaimo Group, the Comox Formation (Fm), comprises strata that are neither time correlative nor genetically related. The three lithostratigraphic units directly overlying the Comox Fm (Haslam, Extension, and Protection formations) comprise strata with similar genetic affinities and MDAs that indicate deposition of these units was not always sequential and locally was contemporaneous. Through this work, we provide an example of how MDAs from DZ geochronology in CMBs can resolve basin-scale stratigraphic relations, and identify chronological changes in sediment provenance.
Crystal structure of the catalytic unit of GH 87-type α-1,3-glucanase Agl-KA from Bacillus circulans
Authors: Yano Shigekazu , Suyotha Wasana , Oguro Natsuki , Matsui Takashi , Shiga Shota , Itoh Takafumi , Hibi Takao , Tanaka Yoshikazu , Wakayama Mamoru , Makabe Koki 
Published: October 2019

AbstractGlycoside hydrolase (GH) 87-type α-1,3-glucanase hydrolyses the α-1,3-glucoside linkages of α-1,3-glucan, which is found in fungal cell walls and extracellular polysaccharides produced by oral Streptococci. In this study, we report on the molecular structure of the catalytic unit of GH 87-type α-1,3-glucanase, Agl-KA, from Bacillus circulans, as determined by x-ray crystallography at a resolution of 1.82 Å. The catalytic unit constitutes a complex structure of two tandemly connected domains—the N-terminal galactose-binding-like domain and the C-terminal right-handed β-helix domain. While the β-helix domain is widely found among polysaccharide-processing enzymes, complex formation with the galactose-binding-like domain was observed for the first time. Biochemical assays showed that Asp1067, Asp1090 and Asp1091 are important for catalysis, and these residues are indeed located at the putative substrate-binding cleft, which forms a closed end and explains the product specificity.
A Curriculum Learning Strategy to Enhance the Accuracy of Classification of Various Lesions in Chest-PA X-ray Screening for Pulmonary Abnormalities
Authors: Park Beomhee , Cho Yongwon , Lee Gaeun , Lee Sang Min , Cho Young-Hoon , Lee Eun Sol , Lee Kyung Hee , Seo Joon Beom , Kim Namkug 
Published: October 2019

AbstractWe evaluated the efficacy of a curriculum learning strategy using two steps to detect pulmonary abnormalities including nodule[s], consolidation, interstitial opacity, pleural effusion, and pneumothorax with chest-PA X-ray (CXR) images from two centres. CXR images of 6069 healthy subjects and 3417 patients at AMC and 1035 healthy subjects and 4404 patients at SNUBH were obtained. Our approach involved two steps. First, the regional patterns of thoracic abnormalities were identified by initial learning of patch images around abnormal lesions. Second, Resnet-50 was fine-tuned using the entire images. The network was weakly trained and modified to detect various disease patterns. Finally, class activation maps (CAM) were extracted to localise and visualise the abnormal patterns. For average disease, the sensitivity, specificity, and area under the curve (AUC) were 85.4%, 99.8%, and 0.947, respectively, in the AMC dataset and 97.9%, 100.0%, and 0.983, respectively, in the SNUBH dataset. This curriculum learning and weak labelling with high-scale CXR images requires less preparation to train the system and could be easily extended to include various diseases in actual clinical environments. This algorithm performed well for the detection and classification of five disease patterns in CXR images and could be helpful in image interpretation.
Accelerating river blindness elimination by supplementing MDA with a vegetation “slash and clear” vector control strategy: a data-driven modeling analysis
Authors: Smith Morgan E. , Bilal Shakir , Lakwo Thomson L. , Habomugisha Peace , Tukahebwa Edridah , Byamukama Edson , Katabarwa Moses N. , Richards Frank O. , Cupp Eddie W. , Unnasch Thomas R. , Michael Edwin 
Published: October 2019

AbstractAttention is increasingly focusing on how best to accelerate progress toward meeting the WHO’s 2030 goals for neglected tropical diseases (NTDs). For river blindness, a major NTD targeted for elimination, there is a long history of using vector control to suppress transmission, but traditional larvicide-based approaches are limited in their utility. One innovative and sustainable approach, “slash and clear”, involves clearing vegetation from breeding areas, and recent field trials indicate that this technique very effectively reduces the biting density of Simulium damnosum s.s. In this study, we use a Bayesian data-driven mathematical modeling approach to investigate the potential impact of this intervention on human onchocerciasis infection. We developed a novel “slash and clear” model describing the effect of the intervention on seasonal black fly biting rates and coupled this with our population dynamics model of Onchocerca volvulus transmission. Our results indicate that supplementing annual drug treatments with “slash and clear” can significantly accelerate the achievement of onchocerciasis elimination. The efficacy of the intervention is not very sensitive to the timing of implementation, and the impact is meaningful even if vegetation is cleared only once per year. As such, this community-driven technique will represent an important option for achieving and sustaining O. volvulus elimination.
Survey of bacteria associated with western corn rootworm life stages reveals no difference between insects reared in different soils
Authors: Ludwick Dalton C. , Ericsson Aaron C. , Meihls Lisa N. , Gregory Michelle L. J. , Finke Deborah L. , Coudron Thomas A. , Hibbard Bruce E. , Shelby Kent S. 
Published: October 2019

AbstractWestern corn rootworm (Diabrotica virgifera virgifera LeConte) is a serious pest of maize (Zea mays L.) in North America and parts of Europe. With most of its life cycle spent in the soil feeding on maize root tissues, this insect is likely to encounter and interact with a wide range of soil and rhizosphere microbes. Our knowledge of the role of microbes in pest management and plant health remains woefully incomplete, yet that knowledge could play an important role in effective pest management strategies. For this study, insects were reared on maize in soils from different locations. Insects from two different laboratory colonies (a diapausing and a non-diapausing colony) were sampled at each life stage to determine the possible core bacteriome. Additionally, soil was sampled at each life stage and resulting bacteria were identified to determine the possible contribution of soil to the rootworm bacteriome, if any. We analyzed the V4 hypervariable region of bacterial 16S rRNA genes with Illumina MiSeq to survey the different species of bacteria associated with the insects and the soils. The bacterial community associated with insects was significantly different from that in the soil. Some differences appear to exist between insects from non-diapausing and diapausing colonies while no significant differences in community composition existed between the insects reared on different soils. Despite differences in the bacteria present in immature stages and in male and female adults, there is a possible core bacteriome of approximately 16 operational taxonomic units (i.e., present across all life stages). This research may provide insights into Bt resistance development, improved nutrition in artificial rearing systems, and new management strategies.
Genome-wide differential expression profiling of lncRNAs and mRNAs associated with early diabetic cardiomyopathy
Authors: Pant Tarun , Dhanasekaran Anuradha , Bai Xiaowen , Zhao Ming , Thorp Edward B. , Forbess Joseph M. , Bosnjak Zeljko J. , Ge Zhi-Dong 
Published: October 2019

AbstractDiabetic cardiomyopathy is one of the main causes of heart failure and death in patients with diabetes. There are no effective approaches to preventing its development in the clinic. Long noncoding RNAs (lncRNA) are increasingly recognized as important molecular players in cardiovascular disease. Herein we investigated the profiling of cardiac lncRNA and mRNA expression in type 2 diabetic db/db mice with and without early diabetic cardiomyopathy. We found that db/db mice developed cardiac hypertrophy with normal cardiac function at 6 weeks of age but with a decreased diastolic function at 20 weeks of age. LncRNA and mRNA transcripts were remarkably different in 20-week-old db/db mouse hearts compared with both nondiabetic and diabetic controls. Overall 1479 lncRNA transcripts and 1109 mRNA transcripts were aberrantly expressed in 6- and 20-week-old db/db hearts compared with nondiabetic controls. The lncRNA-mRNA co-expression network analysis revealed that 5 deregulated lncRNAs having maximum connections with differentially expressed mRNAs were BC038927, G730013B05Rik, 2700054A10Rik, AK089884, and Daw1. Bioinformatics analysis revealed that these 5 lncRNAs are closely associated with membrane depolarization, action potential conduction, contraction of cardiac myocytes, and actin filament-based movement of cardiac cells. This study profiles differently expressed lncRNAs in type 2 mice with and without early diabetic cardiomyopathy and identifies BC038927, G730013B05Rik, 2700054A10Rik, AK089884, and Daw1 as the core lncRNA with high significance in diabetic cardiomyopathy.
BCG instillation versus radical cystectomy for high-risk NMIBC with squamous/glandular histologic variants
Authors: Suh Jungyo , Moon Kyung Chul , Jung Jae Hyun , Lee Junghoon , Song Won Hoon , Kang Yu Jin , Jeong Chang Wook , Kwak Cheol , Kim Hyeon Hoe , Ku Ja Hyeon 
Published: October 2019

AbstractThis study aims to evaluate the effect of Bacillus Calmette-Guérin (BCG) instillation and radical cystectomy on high-risk NMIBC with squamous or glandular variants. We retrospectively reviewed the data of high-risk (T1 or CIS or HG or TaG1/G2 with multiple, recurrent, large tumor) NMIBC patients from January 2000 to December 2017. Comparative analysis of radical cystectomy, intravesical BCG, and observation groups was conducted in high-risk NMIBC with squamous or glandular histologic variants. Among the 1263 high-risk NMIBC patient, 62 (4.9%) were reported squamous or glandular histologic variants. Thirty patients underwent BCG instillation and 15 patients were subjected to radical cystectomy. Statistically significant differences were found between the three treatment groups in terms of underlying hypertension (p = 0.031), T stage (p = 0.022) and tumor multiplicity (p = 0.019). Similar 5-year OS (p = 0.893) and CSS (p = 0.811) were observed in each of BCG instillation and radical cystectomy group. BCG instillation showed survival benefit in both OS (p = 0.019) and CSS (p = 0.038) than in the observation group. In high-risk patients diagnosed with NMIBC bladder cancer with squamous or glandular histologic variants, both intravesical BCG and radical cystectomy showed survival gain. In conclusion, BCG instillation represents an appropriate treatment option in high-risk NMIBC with squamous or glandular histologic variant.
Molecular signatures associated with prostate cancer cell line (PC-3) exposure to inactivated Zika virus
Authors: Delafiori Jeany , Lima Estela de Oliveira , Dabaja Mohamed Ziad , Dias-Audibert Flávia Luísa , de Oliveira Diogo Noin , Melo Carlos Fernando Odir Rodrigues , Morishita Karen Noda , Sales Geovana Manzan , Ruiz Ana Lucia Tasca Gois , da Silva Gisele Goulart , Lancellotti Marcelo , Catharino Rodrigo Ramos 
Published: October 2019

AbstractThe recent outbreak of Zika virus (ZIKV) infection associated with microcephaly cases has elicited much research on the mechanisms involved in ZIKV-host cell interactions. It has been described that Zika virus impairs cell growth, raising a hypothesis about its oncolytic potential against cancer cells. ZIKV tumor cell growth inhibition was later confirmed for glioblastoma. It was also demonstrated that an inactivated ZIKV prototype (ZVp) based on bacterial outer membrane vesicles has antiproliferative activity upon other cancer cell lines, such as PC-3 prostate cancer cell. This study aims at understanding the pathways that might be involved with the antiproliferative effect of Zika virus against prostate cancer cells. A metabolomic approach based on high-resolution mass spectrometry analysis led to the identification of 21 statistically relevant markers of PC-3 cells treated with ZVp. The markers were associated with metabolic alterations that trigger lipid remodeling, endoplasmic reticulum stress, inflammatory mediators, as well as disrupted porphyrin and folate metabolism. These findings highlight molecular signatures of ZVp-induced response that may be involved on cellular pathways triggered by its antiproliferative effect. To our knowledge, this is the first reported metabolomic assessment of ZIKV effect on prostate cancer cells, a promising topic for further research.
Disparities in the Concentrations of Essential/Toxic Elements in the Blood and Scalp Hair of Lymphoma Patients and Healthy Subjects
Authors: Qayyum Muhammad Abdul , Shah Munir H. 
Published: October 2019

AbstractLymphoma is one of the fastest growing malignancies worldwide and imbalance in the concentrations of trace elements can play a significant role in the onset and progression of the disease. Selected essential and toxic elements (Fe, Zn, Cu, Mn, Ni, Cr, Cd and Pb) were analysed in the blood & scalp hair of lymphoma patients (n = 59 & 58, respectively) and controls (n = 61 & 60, respectively) by atomic absorption spectrometry. On the average, Ni, Cr, Cu and Cd revealed significantly higher contents in the blood and scalp hair of the patients than the controls (p < 0.05). The correlation study showed significantly diverse relationships among the elements in blood & scalp hair of the two donor groups. Variations in the elemental levels with different types of lymphoma (non-Hodgkin and Hodgkin) were also evaluated. Disparities in the elemental concentrations were also investigated for various types of non-Hodgkin (diffuse large B-cell lymphoma, follicular lymphoma and peripheral T-cell lymphoma) and Hodgkin lymphoma (mixed cellularity, nodular lymphocyte predominant and nodular sclerosing), as well as for different stages (I, II, III & IV) of the cancer. Multivariate statistical analysis showed considerably divergent associations of the elements in the patients and controls. The study indicated profound alteration of the elemental levels in the patients; it may be implicated in elemental-induced disorders including lymphoma.