bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated metabolomics and gut microbiome to the effects and mechanisms of naoxintong capsule on type 2 diabetes in rats
Authors: Yan Zenghao , Wu Hao , Zhou Haokui , Chen Shuo , He Yan , Zhang Weijian , Chen Taobin , Yao Hongliang , Su Weiwei 
Published: July 2020

AbstractNaoxintong Capsule (NXT) is a Traditional Chinese Medicine formulation which has been widely applied in treating cardiovascular and cerebrovascular diseases. Previous studies also reported the potential effects of NXT against diabetes and certain complications, yet its mechanisms remain largely obscured. Herein, in this study, we investigated the anti-diabetic effects of NXT as well as its potential mechanisms. Type 2 diabetes (T2D) was induced in rats by 10-week high-fat diet in companion with a low-dose streptozotocin injection. NXT was administrated for additional 8 weeks. The results showed that NXT exerted potent efficacy against T2D by alleviating hyperglycemia and hyperlipidemia, ameliorating insulin resistance, mitigating inflammation, relieving hypertension, and reducing myocardial injuries. To investigate its mechanisms, by integrating sequencing of gut microbiota and serum untargeted metabolomics, we showed that NXT could significantly recover the disturbances of gut microbiota and metabolic phenotypes in T2D rats. Several feature pathways, such as arachidonic acid metabolism, fatty acid β-oxidation and glycerophospholipid metabolism, were identified as the potential mechanisms of NXT in vivo. In summary, our study has comprehensively revealed the anti-diabetic effects of NXT which could be considered as a promising strategy for treating metabolic disorders, T2D and diabetic related complications in clinical practice.
Identification of the amino acid position controlling the different enzymatic activities in walnut tyrosinase isoenzymes (jrPPO1 and jrPPO2)
Authors: Panis Felix , Rompel Annette 
Published: July 2020

AbstractPolyphenol oxidases (PPOs) are ubiquitously distributed among plants, bacteria, fungi and animals. They catalyze the hydroxylation of monophenols (monophenolase activity) and the oxidation of o-diphenols (diphenolase activity) to o-quinones. PPOs are commonly present as an isoenzyme family. In walnut (Juglans regia), two different genes (jrPPO1 and jrPPO2) encoding PPOs have been identified. In this study, jrPPO2 was, for the first time, heterologously expressed in E. coli and characterized as a tyrosinase (TYR) by substrate scope assays and kinetic investigations, as it accepted tyramine and L-tyrosine as substrates. Moreover, the substrate acceptance and kinetic parameters (kcat and Km values) towards 16 substrates naturally present in walnut were assessed for jrPPO2 (TYR) and its isoenzyme jrPPO1 (TYR). The two isoenzymes prefer different substrates, as jrPPO1 shows a higher activity towards monophenols, whereas jrPPO2 is more active towards o-diphenols. Molecular docking studies performed herein revealed that the amino acid residue in the position of the 1st activity controller (HisB1 + 1; in jrPPO1 Asn240 and jrPPO2 Gly240) is responsible for the different enzymatic activities. Additionally, interchanging the 1st activity controller residue of the two enzymes in two mutants (jrPPO1-Asn240Gly and jrPPO2-Gly240Asn) proved that the amino acid residue located in this position allows plants to selectively target or dismiss substrates naturally present in walnut.
Immune status, and not HIV infection or exposure, drives the development of the oral microbiota
Authors: Coker M. O. , Mongodin E. F. , El-Kamary S. S. , Akhigbe P. , Obuekwe O. , Omoigberale A. , Langenberg P. , Enwonwu C. , Hittle L. , Blattner W. A. , Charurat M. 
Published: July 2020

AbstractEven with antiretroviral therapy, children born to HIV-infected (HI) mothers are at a higher risk of early-life infections and morbidities including dental disease. The increased risk of dental caries in HI children suggest immune-mediated changes in oral bacterial communities, however, the impact of perinatal HIV exposure on the oral microbiota remains unclear. We hypothesized that the oral microbiota of HI and perinatally HIV-exposed-but-uninfected (HEU) children will significantly differ from HIV-unexposed-and-uninfected (HUU) children. Saliva samples from 286 child-participants in Nigeria, aged ≤ 6 years, were analyzed using 16S rRNA gene sequencing. Perinatal HIV infection was significantly associated with community composition (HI vs. HUU—p = 0.04; HEU vs. HUU—p = 0.11) however, immune status had stronger impacts on bacterial profiles (p < 0.001). We observed age-stratified associations of perinatal HIV exposure on community composition, with HEU children differing from HUU children in early life but HEU children becoming more similar to HUU children with age. Our findings suggest that, regardless of age, HIV infection or exposure, low CD4 levels persistently alter the oral microbiota during this critical developmental period. Data also indicates that, while HIV infection clearly shapes the developing infant oral microbiome, the effect of perinatal exposure (without infection) appears transient.
Selective whole genome amplification of Plasmodium malariae DNA from clinical samples reveals insights into population structure
Authors: Ibrahim Amy , Diez Benavente Ernest , Nolder Debbie , Proux Stephane , Higgins Matthew , Muwanguzi Julian , Gomez Gonzalez Paula Josefina , Fuehrer Hans-Peter , Roper Cally , Nosten Francois , Sutherland Colin , Clark Taane G. , Campino Susana 
Published: July 2020

AbstractThe genomic diversity of Plasmodium malariae malaria parasites is understudied, partly because infected individuals tend to present with low parasite densities, leading to difficulties in obtaining sufficient parasite DNA for genome analysis. Selective whole genome amplification (SWGA) increases the relative levels of pathogen DNA in a clinical sample, but has not been adapted for P. malariae parasites. Here we design customized SWGA primers which successfully amplify P. malariae DNA extracted directly from unprocessed clinical blood samples obtained from patients with P. malariae-mono-infections from six countries, and further test the efficacy of SWGA on mixed infections with other Plasmodium spp. SWGA enables the successful whole genome sequencing of samples with low parasite density (i.e. one sample with a parasitaemia of 0.0064% resulted in 44% of the genome covered by ≥ 5 reads), leading to an average 14-fold increase in genome coverage when compared to unamplified samples. We identify a total of 868,476 genome-wide SNPs, of which 194,709 are unique across 18 high-quality isolates. After exclusion of the hypervariable subtelomeric regions, a high-quality core subset of 29,899 unique SNPs is defined. Population genetic analysis suggests that P. malariae parasites display clear geographical separation by continent. Further, SWGA successfully amplifies genetic regions of interest such as orthologs of P. falciparum drug resistance-associated loci (Pfdhfr, Pfdhps, Pfcrt, Pfk13 and Pfmdr1), and several non-synonymous SNPs were detected in these genes. In conclusion, we have established a robust SWGA approach that can assist whole genome sequencing of P. malariae, and thereby facilitate the implementation of much-needed large-scale multi-population genomic studies of this neglected malaria parasite. As demonstrated in other Plasmodia, such genetic diversity studies can provide insights into the biology underlying the disease and inform malaria surveillance and control measures.
Evolution of ferroelectricity in ultrathin PbTiO3 films as revealed by electric double layer gating
Authors: Nishino Ryutaro , Fujita Takahiro C. , Kagawa Fumitaka , Kawasaki Masashi 
Published: July 2020

AbstractFerroelectricity in ultrathin films is destabilized by depolarization field, which leads to the reduction of spontaneous polarization or domain formation. Here, thickness dependence of remnant polarization in PbTiO3 films is electrically revealed down to 2.6 nm by controlling the polarization direction with employing an electric double layer gating technique to suppress leakage current in ultrathin films. The remnant polarization for a 17 nm-thick film is similar to bulk value ~ 60 μC cm−2 and reduces to ~ 20 μC cm−2 for a 2.6 nm-thick film, whereas robust ferroelectricity is clearly observed in such ultrathin films. In-situ X-ray diffraction measurements under an external electric field reveal that the reduced tetragonality in ultrathin films is mostly recovered by cancelling out the depolarization field. Electric double layer gating technique is an excellent way for exploring physical properties in ultrathin ferroelectric films.
Environmental context determines the limiting demographic processes for plant recruitment across a species’ elevational range
Authors: Merges Dominik , Albrecht Jörg , Böhning-Gaese Katrin , Schleuning Matthias , Neuschulz Eike Lena 
Published: July 2020

AbstractPlant recruitment is a multi-stage process determining population dynamics and species distributions. Still, we have limited understanding of how the successive demographic processes depend on the environmental context across species’ distributional ranges. We conducted a large-scale transplant experiment to study recruitment of Pinus cembra over six years. We quantified the effects of environmental conditions on four demographic processes and identified the most limiting across and beyond the pines’ elevational range over several years. Realized transition probabilities of the demographic processes varied substantially across the species' distributional range. Seed deposition decreased from the lower to the upper elevational range margin by 90%, but this reduction was offset by increased seed germination and seedling survival. Dispersal limitation at the upper range margin potentially stems from unsuitable seed caching conditions for the animal seed disperser, whereas increased seed germination might result from enemy escape from fungal pathogens and favourable abiotic conditions at the upper range margin. Our multi-year experiment demonstrates that environmental context is decisive for the local relevance of particular demographic processes. We conclude that experimental studies identifying the limiting demographic processes controlling species distributions are key for projecting future range dynamics of plants.
Study of factors influencing preoperative detection of alveolar antral artery by CBCT in sinus floor elevation
Authors: Varela-Centelles Pablo , Loira María , González-Mosquera Antonio , Romero-Mendez Amparo , Seoane Juan , García-Pola María José , Seoane-Romero Juan M. 
Published: July 2020

AbstractThis study aimed at assessing the prevalence of alveolar antral artery (AAA) detection by CBCT, its related variables, and at describing explanatory models useful in surgical planning, by retrospective evaluation of CBCT explorations. The modelling of the probability for detecting AAA was undertaken using logistic generalized additive models (GAM). The capacity for discriminating detection/no detection was assessed by receiver operating characteristic curves. A total of 466 sinuses were studied. Univariate models showed detection probability was linked to sinus width and thickness of the lateral bony wall, together with the shape and height of the osseous crest. AAA detection probability increased steadily until the thickness of the bony wall reached 6 mm. Multivariate models resulted good discriminators for AAA detection, particularly for females, showing an area under the curve (AUC) of 0.85. Models considering patients altogether, and those including only males offered slightly lower values (AUC = 0.79). The probability of AAA detection by CBCT was influenced by gender (higher in males and for narrow sinuses) and increases with the thickness of the sinus lateral bony wall and the height of the residual alveolar ridge. Besides, and particularly for women, the thickness of the ridge at the basal level seems to improve the explanatory model for AAA detection.
An expanded repertoire of intensity-dependent exercise-responsive plasma proteins tied to loci of human disease risk
Authors: Guseh J. Sawalla , Churchill Timothy W. , Yeri Ashish , Lo Claire , Brown Marcel , Houstis Nicholas E. , Aragam Krishna G. , Lieberman Daniel E. , Rosenzweig Anthony , Baggish Aaron L. 
Published: July 2020

AbstractRoutine endurance exercise confers numerous health benefits, and high intensity exercise may accelerate and magnify many of these benefits. To date, explanatory molecular mechanisms and the influence of exercise intensity remain poorly understood. Circulating factors are hypothesized to transduce some of the systemic effects of exercise. We sought to examine the role of exercise and exercise intensity on the human plasma proteome. We employed an aptamer-based method to examine 1,305 plasma proteins in 12 participants before and after exercise at two physiologically defined intensities (moderate and high) to determine the proteomic response. We demonstrate that the human plasma proteome is responsive to acute exercise in an intensity-dependent manner with enrichment analysis suggesting functional biological differences between the moderate and high intensity doses. Through integration of available genetic data, we estimate the effects of acute exercise on exercise-associated traits and find proteomic responses that may contribute to observed clinical effects on coronary artery disease and blood pressure regulation. In sum, we provide supportive evidence that moderate and high intensity exercise elicit different signaling responses, that exercise may act in part non-cell autonomously through circulating plasma proteins, and that plasma protein dynamics can simulate some the beneficial and adverse effects of acute exercise.
An important role of PHRF1 in dendritic architecture and memory formation by modulating TGF-β signaling
Authors: Shih Ting-Wei , Lee Li-Jen , Chang Ho-Ching , Lin Hung-Wei , Chang Mau-Sun 
Published: July 2020

AbstractPHRF1 is involved in transforming growth factor β (TGF-β) signaling to constrain the formation of acute promyelocytic leukemia (APL) in mouse APL models. PHRF1 also participates in modulating non-homologous end-joining. However, the role of PHRF1 in mammalian dendrite architecture and synaptic plasticity is unclear. Here, we investigated the role of PHRF1 in dendritic formation in the murine hippocampus using Camk2a promoter driven-iCre recombinase to conduct a PHRF1 conditional knockout, namely PHRF1Δ/Δ, in the forebrain region. PHRF1Δ/Δmice developed normally, but exhibited anxiety-like behaviors and displayed defective spatial memory. Alterations of dendritic complexity in apical and basal dendrites of pyramidal neurons were noticed in PHRF1Δ/Δmutants. Furthermore, electrical stimulation in the hippocampal CA1 region after the TGF-β1 treatment showed a reduced synaptic plasticity in PHRF1Δ/Δmice. Immunoblotting analysis indicated that PHRF1 ablation affected the TGF-β signaling. Collectively, our results demonstrate that PHRF1 is important for the dendritic architecture and required for spatial memory formation in the hippocampus.
Maternal and fetal cardiovascular and metabolic effects of intra-operative uterine handling under general anesthesia during pregnancy in sheep
Authors: Shaw Caroline J. , Botting Kimberley J. , Niu Youguo , Lees Christoph C. , Giussani Dino A. 
Published: July 2020

AbstractA cohort study of 6,500,000 human pregnancies showed an increased risk of adverse fetal outcomes following abdominal but not non-abdominal surgery under general anesthesia. This may be the consequence of uterine handling during abdominal surgery. However, there are no data on any effects on the cardiometabolic physiology of the fetus or mother in response to uterine manipulation in otherwise healthy pregnancy. Consequently, 9 sheep in late gestation were anesthetized with isofluorane and maternal and fetal catheters and flow probes were implanted to determine cardiovascular and metabolic changes during uterine handling. Uterine handling led to an acute increase in uterine artery vascular resistance, fetal peripheral vasoconstriction, a reduction in oxygen delivery to the femoral circulation, worsening fetal acidosis. There was no evidence of systemic fetal hypoxia, or changes in fetal heart rate, carotid blood flow or carotid oxygen delivery. Therefore, the data support that uterine handling during abdominal surgery under general anesthesia can impact adversely on fetal cardiometabolic health. This may provide a potential explanation linking adverse fetal outcomes in abdominal compared with non-abdominal surgery during pregnancy. The data have important implications for human fetal surgery where the uterus is handled, as operative procedures during late gestation under general maternal anesthesia become more prevalent.
Altered iron metabolism in cystic fibrosis macrophages: the impact of CFTR modulators and implications for Pseudomonas aeruginosa survival
Authors: Hazlett H. F. , Hampton T. H. , Aridgides D. S. , Armstrong D. A. , Dessaint J. A. , Mellinger D. L. , Nymon A. B. , Ashare A. 
Published: July 2020

AbstractCystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in chronic bacterial lung infections and tissue damage. CF macrophages exhibit reduced bacterial killing and increased inflammatory signaling. Iron is elevated in the CF lung and is a critical nutrient for bacteria, including the common CF pathogen Pseudomonas aeruginosa (Pa). While macrophages are a key regulatory component of extracellular iron, iron metabolism has yet to be characterized in human CF macrophages. Secreted and total protein levels were analyzed in non-CF and F508del/F508del CF monocyte derived macrophages (MDMs) with and without clinically approved CFTR modulators ivacaftor/lumacaftor. CF macrophage transferrin receptor 1 (TfR1) was reduced with ivacaftor/lumacaftor treatment. When activated with LPS, CF macrophage expressed reduced ferroportin (Fpn). After the addition of exogenous iron, total iron was elevated in conditioned media from CF MDMs and reduced in conditioned media from ivacaftor/lumacaftor treated CF MDMs. Pa biofilm formation and viability were elevated in conditioned media from CF MDMs and biofilm formation was reduced in the presence of conditioned media from ivacaftor/lumacaftor treated CF MDMs. Defects in iron metabolism observed in this study may inform host–pathogen interactions between CF macrophages and Pa.
Web portal for analytical validation of MRM-MS assay abided with integrative multinational guidelines
Authors: Kim Jaenyeon , Yeo Injoon , Kim Hyunsoo , Sohn Areum , Kim Yoseop , Kim Youngsoo 
Published: July 2020

AbstractMultiple reaction monitoring-mass spectrometry became a mainstream method for quantitative proteomics, which made the validation of a method and the analyzed data important. In this portal for validation of the MRM-MS assay, we developed a website that automatically evaluates uploaded MRM-MS data, based on biomarker assay guidelines from the European Medicines Agency, the US Food & Drug Administration, and the Korea Food & Drug Administration. The portal reads a Skyline output file and produces the following results—calibration curve, specificity, sensitivity, carryover, precision, recovery, matrix effect, recovery, dilution integrity, stability, and QC—according to the standards of each independent agency. The final tables and figures that pertain to the 11 evaluation categories are displayed in an individual page. Spring boot was used as a framework for development of the webpage, which follows MVC Pattern. JSP, HTML, XML, and Java Script were used to develop the webpage. A server was composed of Apache Tomcat, MySQL. Input files were skyline-derived output files (csv file), and each files were organized by specific columns in order. SQL, JAVA were interworked to evaluate all the categories and show the results. Method Validation Portal can be accessed via any kind of explorer from https://pnbvalid.snu.ac.kr.
Identification and functional analysis of five genes that encode distinct isoforms of protein phosphatase 1 in Nilaparvata lugens
Authors: Wang Weixia , Zhu Tingheng , Lai Fengxiang , Wan Pinjun , Wei Qi , Fu Qiang 
Published: July 2020

AbstractTen distinct cDNAs encoding five different protein phosphatases 1 (PPP1) were cloned from Nilaparvata lugens. NlPPP1α and NlPPP1β are highly conserved whereas NlPPP1-Y, NlPPP1-Y1 and NlPPP1-Y2 are lowly conserved among insects. NlPPP1α and NlPPP1β exhibited a ubiquitous expression, while NlPPP1-Y, NlPPP1-Y1, and NlPPP1-Y2 were obviously detected from the 4th instar nymph to imago developmental stages in males, especially detected in internal reproductive organ and fat bodies of the male. Injection nymphs with dsRNA of NlPPP1α or NlPPP1β was able to reduce the target gene expression in a range of 71.5–91.0%, inducing a maximum mortality rate of 95.2% or 97.2% at 10th day after injection and eclosion ratio down by 65.5–100.0%. Injection with dsNlPPP1Ys targeted to NlPPP1-Y, NlPPP1-Y1and NlPPP1-Y2 was able to induce a maximum mortality rate of 95.5% at 10th day after injection, eclosion ratio down by 86.4%. Knock-down one of the male-biased NlPPP1 genes has no effect on survival and eclosion ratio. Injection of 4th instar nymph with dsNlPPP1Ys led to reduced oviposition amount and hatchability, down by 44.7% and 19.6% respectively. Knock-down of NlPPP1-Y1 or NlPPP1-Y2 gene did not significantly affect oviposition amount but significantly affected hatchability. The results indicate that the male-biased NlPPP1 genes have overlapping functions in N. lugens development, and NlPPP1-Y1 and NlPPP1-Y2 may play important roles in spermatogenesis and fertilization. The dsNlPPP1β and dsNlPPP1Ys in this study could be the preferred sequence in RNAi and low-conserved male-biased NlPPP1 genes could be potential target for N. lugens control.
Quiescent stem cell marker genes in glioma gene networks are sufficient to distinguish between normal and glioblastoma (GBM) samples
Authors: Mukherjee Shradha 
Published: July 2020

AbstractGrade 4 glioma or GBM has poor prognosis and is the most aggressive grade of glioma. Accurate diagnosis and classification of tumor grade is a critical determinant for development of treatment pathway. Extensive genomic sequencing of gliomas, different cell types, brain tissue regions and advances in bioinformatics algorithms, have presented an opportunity to identify molecular markers that can complement existing histology and imaging methods used to diagnose and classify gliomas. ‘Cancer stem cell theory’ purports that a minor population of stem cells among the heterogeneous population of different cell types in the tumor, drive tumor growth and resistance to therapies. However, characterization of stem cell states in GBM and ability of stem cell state signature genes to serve as diagnostic or prognostic molecular markers are unknown. In this work, two different network construction algorithms, Weighted correlation network analysis (WGCNA) and Multiscale Clustering of Geometric Network (MEGENA), were applied on publicly available glioma, control brain and stem cell gene expression RNA-seq datasets, to identify gene network regulatory modules associated with GBM. Both gene network algorithms identified consensus or equivalent modules, HuAgeGBsplit_18 (WGCNA) and c1_HuAgeGBsplit_32/193 (MEGENA), significantly associated with GBM. Characterization of HuAgeGBsplit_18 (WGCNA) and c1_HuAgeGBsplit_32/193 (MEGENA) modules showed significant enrichment of rodent quiescent stem cell marker genes (GSE70696_QNPbyTAP). A logistic regression model built with eight of these quiescent stem cell marker genes (GSE70696_QNPbyTAP) was sufficient to distinguish between control and GBM samples. This study demonstrates that GBM associated gene regulatory modules are characterized by diagnostic quiescent stem cell marker genes, which may potentially be used clinically as diagnostic markers and therapeutic targets in GBM.