bluuebunny/crossref_metadata_2025 huggingface dataset:
A Facile Route for the Preparation of Monodisperse Iron nitride at Silica Core/shell Nanostructures
Authors: Kim Hoonsub , Im Pyung Won , Piao Yuanzhe
Published: September 2021

Uniform-sized iron oxide nanoparticles obtained from the solution phase thermal decomposition of the iron-oleate complex were encapsulated inside the silica shell by the reverse microemulsion technique, and then thermal treatment under NH3 to transfer the iron oxide to iron nitride. The transmission electron microscopy images distinctly demonstrated that the as-prepared iron nitride at silica core/shell nanostructures were highly uniform in particle-size distribution. By using iron oxide nanoparticles of 6.1, 10.3, 16.2, and 21.8 nm as starting materials, iron nitride nanoparticles with average diameters of 5.6, 9.3, 11.6, and 16.7 nm were produced, respectively. The acid-resistant properties of the iron nitride at silica core/shell nanostructures were found to be much higher than the starting iron oxide at silica. A superconducting quantum interference device was used for the magnetic characterization of the nanostructure. Besides, magnetic resonance imaging (MRI) studies using iron nitride at silica nanocomposites as contrast agents demonstrated T2 enhanced effects that were dependent on the concentration. These core/shell nanostructures have enormous potential in magnetic nanodevice and biomedical applications. The current process is expected to be easy for large-scale and transfer other metal oxide nanoparticles.
RNA-Binding Proteins in the Post-transcriptional Control of Skeletal Muscle Development, Regeneration and Disease
Authors: Shi De-Li , Grifone Raphaëlle
Published: September 2021

Embryonic myogenesis is a temporally and spatially regulated process that generates skeletal muscle of the trunk and limbs. During this process, mononucleated myoblasts derived from myogenic progenitor cells within the somites undergo proliferation, migration and differentiation to elongate and fuse into multinucleated functional myofibers. Skeletal muscle is the most abundant tissue of the body and has the remarkable ability to self-repair by re-activating the myogenic program in muscle stem cells, known as satellite cells. Post-transcriptional regulation of gene expression mediated by RNA-binding proteins is critically required for muscle development during embryogenesis and for muscle homeostasis in the adult. Differential subcellular localization and activity of RNA-binding proteins orchestrates target gene expression at multiple levels to regulate different steps of myogenesis. Dysfunctions of these post-transcriptional regulators impair muscle development and homeostasis, but also cause defects in motor neurons or the neuromuscular junction, resulting in muscle degeneration and neuromuscular disease. Many RNA-binding proteins, such as members of the muscle blind-like (MBNL) and CUG-BP and ETR-3-like factors (CELF) families, display both overlapping and distinct targets in muscle cells. Thus they function either cooperatively or antagonistically to coordinate myoblast proliferation and differentiation. Evidence is accumulating that the dynamic interplay of their regulatory activity may control the progression of myogenic program as well as stem cell quiescence and activation. Moreover, the role of RNA-binding proteins that regulate post-transcriptional modification in the myogenic program is far less understood as compared with transcription factors involved in myogenic specification and differentiation. Here we review past achievements and recent advances in understanding the functions of RNA-binding proteins during skeletal muscle development, regeneration and disease, with the aim to identify the fundamental questions that are still open for further investigations.
Permeability Data of Organosulfur Garlic Compounds Estimated by Immobilized Artificial Membrane Chromatography: Correlation Across Several Biological Barriers
Authors: Ramirez Daniela Andrea , Federici María Fernanda , Altamirano Jorgelina Cecilia , Camargo Alejandra Beatriz , Luco Juan María
Published: September 2021

Among healthy vegetables, those of the genus Allium stand out. Antioxidant and anti-inflammatory properties have been associated with these vegetables, attributed mainly to organosulfur compounds (OSCs). In turn, they are linked to a protective effect counteracting cardiovascular disease development. Now, to really ensure the bioactive efficacy of the said compounds once consumed, it is necessary to previously evaluate the ADME (absorption, distribution, metabolism, and excretion) profile. Alternatively, in vitro and in silico methods attempt to avoid or reduce experimental animals’ use and provide preliminary information on drugs’ ability to overcome the various biological barriers inherent in the ADME process. In this sense, in silico methods serve to provide primary information on drugs’ bioavailability mechanisms. High-performance liquid chromatography (HPLC) using a stationary phase composed of phospholipids, the so-called immobilized artificial membrane (IAM), has been widely recognized as a valuable alternative method to extract and quantify information about the structure and physicochemical properties of organic compounds which are extensively used in studies of quantitative structure–activity relationships (QSARs). In the present study, the chromatographic capacity factors (log k’ (IAM)) for 28 OSCs were determined by IAM-HPLC. In order to evaluate the ability of the IAM phase in assessing lipophilicity of the compounds under study, several quantitative structure–retention relationships (QSRRs) were derived from exploring fundamental intermolecular interactions that govern the retention of compounds under study on IAM phases. As expected, the hydrophobic factors are of prime importance for the IAM retention of these compounds. However, the molecular flexibility and specific polar interactions expressed by several electronic descriptors (relative negative charge, RNCG, and Mulliken electronegativity) are also involved. We also evaluated the IAM phase ability to assess several ADME parameters for the OSCs under study obtained using the SwissADME web tool integrated into the SwissDrugDesign workspace and the PreADMET web tool. The human gastrointestinal absorption (HIA), blood–brain barrier (BBB) permeation, and skin permeability were investigated through QSAR modeling, using several chemometric approaches. The ADME properties under study are strongly dependent on hydrophobic factors as expressed by log k’(IAM), which provide evidence for the great potential of the IAM phases in the development of QSAR models.
Research on a Fractal Dimension Calculation Method for a Nano-Polymer Microspheres Dispersed System
Authors: Zhao Wenyue , Yan Jinming , Hou Ganggang , Diwu Pengxiang , Liu Tongjing , Hou Jirui , Li Ruolin
Published: September 2021

Polymer microspheres (PMs) are a kind of self-similar volume expansion particle, and their fractal dimension varies with hydration swelling. However, there is no unique fractal dimension calculation method for their characteristics. A new model is established in this paper, which is particular to calculate the fractal dimension of PMs. We carried out swelling hydration experiments and scanning electron microscope (SEM) experiments to verify the new model. The new model and the box-counting model were used to calculate the fractal dimensions of PMs based on the hydration experiment results. Then, a comparison of the calculation results of the two methods was used to verify the validity of the model. Finally, according to the new model calculation results, the fractal dimension characteristics of PMs were analyzed. The research results indicate that the new model successfully correlates the cumulative probability of the PMs dispersed system with the fractal dimension and makes fractal dimension calculation of PMs more accurate and convenient. Based on the experiment results, the new model was used to calculate the fractal dimension of PMs and the box-counting model, and its findings were all 2.638 at initial state hydration and 2.739 and 2.741 at hydration time as of day 1. This result verifies the correctness of the new model. According to the hydration swelling experiments and the new model calculation results, the fractal dimension is linear correlated to the average particle size of PMs and the standard deviation average particle size. This means the fractal dimension of PMs represents the space occupancy ability and space occupancy effectiveness.
Comparison of Periodontal Bacteria of Edo and Modern Periods Using Novel Diagnostic Approach for Periodontitis With Micro-CT
Authors: Shiba Takahiko , Komatsu Keiji , Sudo Takeaki , Sawafuji Rikai , Saso Aiko , Ueda Shintaroh , Watanabe Takayasu , Nemoto Takashi , Kano Chihiro , Nagai Takahiko , Ohsugi Yujin , Katagiri Sayaka , Takeuchi Yasuo , Kobayashi Hiroaki , Iwata Takanori
Published: September 2021

Ancient dental calculus, formed from dental plaque, is a rich source of ancient DNA and can provide information regarding the food and oral microbiology at that time. Genomic analysis of dental calculus from Neanderthals has revealed the difference in bacterial composition of oral microbiome between Neanderthals and modern humans. There are few reports investigating whether the pathogenic bacteria of periodontitis, a polymicrobial disease induced in response to the accumulation of dental plaque, were different between ancient and modern humans. This study aimed to compare the bacterial composition of the oral microbiome in ancient and modern human samples and to investigate whether lifestyle differences depending on the era have altered the bacterial composition of the oral microbiome and the causative bacteria of periodontitis. Additionally, we introduce a novel diagnostic approach for periodontitis in ancient skeletons using micro-computed tomography. Ancient 16S rDNA sequences were obtained from 12 samples at the Unko-in site (18th-19th century) of the Edo era (1603–1867), a characteristic period in Japan when immigrants were not accepted. Furthermore, modern 16S rDNA data from 53 samples were obtained from a database to compare the modern and ancient microbiome. The microbial co-occurrence network was analyzed based on 16S rDNA read abundance. Eubacterium species, Mollicutes species, and Treponema socranskii were the core species in the Edo co-occurrence network. The co-occurrence relationship between Actinomyces oricola and Eggerthella lenta appeared to have played a key role in causing periodontitis in the Edo era. However, Porphyromonas gingivalis, Fusobacterium nucleatum subsp. vincentii, and Prevotella pleuritidis were the core and highly abundant species in the co-occurrence network of modern samples. These results suggest the possibility of differences in the pathogens causing periodontitis during different eras in history.
The Neutrophil-to-Lymphocyte Ratio Is an Important Indicator Predicting In-Hospital Death in AMI Patients
Authors: Ji Zhenjun , Liu Guiren , Guo Jiaqi , Zhang Rui , Su Yamin , Carvalho Abdlay , Qu Yangyang , Zuo Wenjie , Yao Yuyu , Lin Jie , Ma Genshan
Published: September 2021

Objective: To explore the role of neutrophil-to-lymphocyte ratio (NLR) in predicting the short-term prognosis of NSTEMI and STEMI.

Methods: This study was a single-center, retrospective and observational study. 2618 patients including 1289 NSTMI and 1329 STEMI patients were enrolled from June 2013 to February 2018 in Zhongda Hospital, Southeast University. The demographic information, clinical characteristics, medical history, laboratory examination, treatment, and outcome of individuals at admission and during hospitalization were extracted from the electronic medical record system. Outcome was defined as the all-cause death during hospitalization.

Results: (1) In the NSTEMI group, the ability of NLR in predicting in-hospital death (AUC = 0.746) was higher than the neutrophil-monocyte ratio (NMR) (AUC = 0.654), the platelet-lymphocyte ratio (PLR) (AUC = 0.603) and the lymphocyte-monocyte ratio (LMR) (AUC = 0.685), and also higher than AST (AUC = 0.621), CK (AUC = 0.595), LDH (AUC = 0.653) and TnI (AUC = 0.594). The AUC of NLR in the STEMI group was only 0.621. (2) The optimal cut-off value of NLR in NSTEMI group was 5.509 (Youden index = 0.447, sensitivity = 77.01%, specificity = 67.72%). After adjusting variables including age, sex, diabetes history, smoking history, LDL-C and Cr, the logistic regression showed that the patients with NLR>5.509 had higher hazard risk of death (HR4.356; 95%CI 2.552–7.435; P < 0.001) than the patients with NLR ≤ 5.509. (3) Stratification analysis showed that the in-hospital mortality of patients with NLR > 5.509 was 14.611-fold higher than those with NLR ≤ 5.509 in patients aged <76, much higher than the ratio in patients aged ≥ 76. For patients with creatinine levels ≤ 71, the in-hospital death risk in high NLR group was 10.065-fold higher than in low NLR group (95%CI 1.761–57.514, P = 0.009), while the HR was only 4.117 in patients with creatinine levels > 71. The HR in patients with or without diabetes were 6.586 and 3.375, respectively. The HR in smoking or no smoking patients were 6.646 and 4.145, respectively. The HR in patients with LDL-C ≥ 2.06 or <2.06 were 5.526 and 2.967 respectively.

Conclusion: Compared to NMR, PLR, and LMR, NLR had the best ability in predicting in-hospital death after NSTEMI. Age, creatinine, LDL-C, diabetes and smoking history were all important factors affecting the predictive efficiency in NSTEMI. NLR had the limited predictive ability in STEMI.
Cardiovascular Aging and Physical Activity: Insights From Metabolomics
Authors: Lim Ryan Mao Heng , Koh Angela S.
Published: September 2021

The purpose of this review is to explore how metabolomics can help uncover mechanisms through which physical activity may influence the progression of cardiovascular aging. Cardiovascular aging is a process of functional and structural changes in older adults which can progress to cardiovascular disease. Metabolomics profiling is an investigative tool that can track the diverse changes which occur in human biochemistry with physical activity and aging. This mini review will summarize published investigations in metabolomics and physical activity, with a specific focus on the metabolic pathways that connect physical activity with cardiovascular aging.
Monitoring of Yangtze River Discharge at Datong Hydrometric Station Using Acoustic Tomography Technology
Authors: Zhu Ze-Nan , Zhu Xiao-Hua , Zhang Chuanzheng , Chen Minmo , Zheng Hua , Zhang Zhensheng , Zhong Jiwen , Wei Lixin , Li Qiang , Wang Hua , Li Shuming , Kaneko Arata
Published: September 2021

To continuously monitor the discharge of the Yangtze River, two coastal acoustic tomography (CAT) systems with synchronized transmission were deployed at the Datong hydrometric station of the Yangtze River from July 2018 to January 2021. To accurately estimate the discharge of the Yangtze River, the cross-sectional averaged flow velocity and area data were estimated by establishing two empirical relationships: one between the range-averaged flow velocity measured by acoustic Doppler current profiler (ADCP) and the reciprocal travel time difference measured by CAT, and the other between the ADCP-measured cross-sectional area and the water-surface elevation (stage). Compared with the discharges directly measured by ADCP, our estimation had the root mean square error of 946 m3/s, accounting for 2.5% of the mean discharge. The discharges varied from 10,981 to 81,807 m3/s over the 2.5-years observational period, with a mean of 30,708 m3/s. The annual mean discharge was 29,163 and 34,763 m3/s in 2019 and 2020, respectively. Our monitoring successfully covered two complete flood processes, with a peak discharge of 69,744 (July 17, 2019) and 81,807 m3/s (July 13, 2020). Our study provides an innovative method to achieve accuracy and real-time monitoring of river discharges even during extreme flood events.
METTL3 Is Involved in the Development of Graves’ Disease by Inducing SOCS mRNA m6A Modification
Authors: Song Rong-hua , Du Peng , Gao Chao-qun , Liu Xue-rong , Zhang Jin-an
Published: September 2021

Objective

Epigenetic modifications in RNA are known to play critical roles in cell differentiation through regulating expressions of some key genes including members of the suppressor of cytokine signaling (SOCS) family. The present study aimed to unveil the relationship of SOCS mRNA methylation induced by methyltransferase like 3 (METTL3) with Graves’ disease (GD).

Methods

Differently expressed genes (DEG) in GD tissues were identified using microarray analysis and further validated using CD4+ T cell microarray of GD tissues and isolated peripheral blood mononuclear cells (PBMCs). Furthermore, expressions of METTL3 targeted genes were detected using METTL3 knock-down experiment in RAW264.7 cells.

Results

High throughput microarrays revealed that METTL3 and SOCS molecules were aberrantly expressed in thyroid tissues and CD4+T cells of GD compared to the controls. Bioinformatic analysis was undertaken by searching databases of found genes of the SOCS family that possessed many mRNA m6A modification loci. METTL3 knock-down experiment revealed that expressions of SOCS family members SOCS1, SOCS2, SOCS4, SOCS5, and SOCS6 were increased after METTL3 knock-down.

Conclusions

For the first time, the present study revealed the relationship between m6A modification and GD and indicated that METTL3 may be involved in the development of GD by inducing mRNA m6A methylation modification of SOCS family members.
Hyperthyroidism With Atrial Fibrillation in Children: A Case Report and Review of the Literature
Authors: Subramonian Deepa , Wu Yuwei Juliana , Amed Shazhan , Sanatani Shubhayan
Published: September 2021

Atrial fibrillation is exceedingly rare in children with structurally and functionally normal hearts. We present a novel case of a 15-year-old female with known hyperthyroidism who subsequently developed atrial fibrillation. She had been suffering from fatigue, heat intolerance and myalgias for 6 months. Her initial TSH was 0.01mU/L, and free T4 was 75.4 pmol/L, with a free T3 of >30.8 pmol/L. An electrocardiogram showed atrial fibrillation with a ventricular rate of 141 beats per minute. An echocardiogram demonstrated an enlarged left atrium and ventricle, with mild mitral regurgitation. She was treated with methimazole and underwent synchronized cardioversion. She subsequently returned to a euthyroid state and remained in normal sinus rhythm. In this case, we discuss the physiologic and arrhythmogenic properties of thyroid hormone, with a summary of the existing literature on atrial fibrillation in hyperthyroidism in children. Current guidelines for treatment of atrial fibrillation are also outlined.
Morphologic and Molecular Characterization of Adrenals and Adrenal Rest Affected by Congenital Adrenal Hyperplasia
Authors: Kolli Vipula , da Cunha Isabela Werneck , Kim SunA , Iben James R. , Mallappa Ashwini , Li Tianwei , Gaynor Alison , Coon Steven L. , Quezado Martha M. , Merke Deborah P.
Published: September 2021

Introduction

Adrenocortical hyperplasia and adrenal rest tumor (ART) formation are common in congenital adrenal hyperplasia (CAH). Although driven by excessive corticotropin, much is unknown regarding the morphology and transformation of these tissues. Our study objective was to characterize CAH-affected adrenals and ART and compare with control adrenal and gonadal tissues.

Patients/Methods

CAH adrenals, ART and control tissues were analyzed by histology, immunohistochemistry, and transcriptome sequencing. We investigated protein expression of the ACTH receptor (MC2R), steroidogenic (CYP11B2, CYP11B1, CYB5A) and immune (CD20, CD3, CD68) biomarkers, and delta-like 1 homolog (DLK1), a membrane bound protein broadly expressed in fetal and many endocrine cells. RNA was isolated and gene expression was analyzed by RNA sequencing (RNA-seq) followed by principle component, and unsupervised clustering analyses.

Results

Based on immunohistochemistry, CAH adrenals and ART demonstrated increased zona reticularis (ZR)-like CYB5A expression, compared to CYP11B1, and CYP11B2, markers of zona fasciculata and zona glomerulosa respectively. CYP11B2 was mostly absent in CAH adrenals and absent in ART. DLK1 was present in CAH adrenal, ART, and also control adrenal and testis, but was absent in control ovary. Increased expression of adrenocortical marker MC2R, was observed in CAH adrenals compared to control adrenal. Unlike control tissues, significant nodular lymphocytic infiltration was observed in CAH adrenals and ART, with CD20 (B-cell), CD3 (T-cell) and CD68 (macrophage/monocyte) markers of inflammation. RNA-seq data revealed co-expression of adrenal MC2R, and testis-specific INSL3, HSD17B3 in testicular ART indicating the presence of both gonadal and adrenal features, and high expression of DLK1 in ART, CAH adrenals and control adrenal. Principal component analysis indicated that the ART transcriptome was more similar to CAH adrenals and least similar to control testis tissue.

Conclusions

CAH-affected adrenal glands and ART have similar expression profiles and morphology, demonstrating increased CYB5A with ZR characteristics and lymphocytic infiltration, suggesting a common origin that is similarly affected by the abnormal hormonal milieu. Immune system modulators may play a role in tumor formation of CAH.
Experimental Investigation for a Novel Prototype of a Thermoelectric Power Generator With Heat Pipes
Authors: Liu Yan , Shi Zhaochun , Wang Guohua , Yan YuYing , Zhang Yingchao
Published: September 2021

In order to obtain the power generation of the thermoelectric power generator (TEG) group, a similar structure of the disc sandwich structure and an experimental system are built to analyze the power generation performance and temperature characteristics. To improve heat transfer and move heat from the hot side to the cold side, heat pipes with high thermal conductivity are arranged on the adjacent cold and hot plates of the TEG. The similar sandwich structure has 17 cold plates and 17 hot plates for the TEG pieces, which are connected in series on the circuit. Working conditions are hot air flow and cold water flow; hot air temperature and cold water temperature are set to a fixed temperature. The power generation of a single TEG is tested for verifying linear changes in the power generation performance with temperature differences (Td). Experimental results are that the power generation is improved by the air flow and water flow increasing. The water flow has a smaller effect on the power generation than the air flow. In the cold side of TEG pieces, the temperature of the cold side showed a gradual upward trend, the temperature of the hot side showed a wave trough phenomenon, and the Td showed a wave trough phenomenon. The hot air flow and the cold water changing cannot weaken the temperature trend of the hot side and the cold side. The hot air flow can more significantly increase the Td than the cold water.
The Impact of Electricity Price on Power-Generation Structure: Evidence From China
Authors: Wang Jing , Li Hong
Published: September 2021

Being affected by a variety of factors, power-generation structure plays an essential role in a high-quality and sustainable development. The focus of this paper is to evaluate the influence of electricity price on it. First, we provide a microeconomic framework to understand the impact mechanism. We discuss two effects through which price level can affect power generation, and then the power-generation structure. After that, an empirical test is conducted using provincial panel data, and the results of it are robust. We also test the above-mentioned mechanism empirically. There are two main conclusions. First, the electricity price has a positive effect on the share of thermal power in electricity generation. Second, the mechanism test shows that an increase of electricity price can not only improve efficiency of power plants but also propel firms to invest in more renewable energy plants.
Good Agreement Between Modeled and Measured Sulfur and Nitrogen Deposition in Europe, in Spite of Marked Differences in Some Sites
Authors: Marchetto Aldo , Simpson David , Aas Wenche , Fagerli Hilde , Hansen Karin , Pihl-Karlsson Gunilla , Karlsson Per Erik , Rogora Michela , Sanders Tanja G. M. , Schmitz Andreas , Seidling Walter , Thimonier Anne , Tsyro Svetlana , de Vries Wim , Waldner Peter
Published: September 2021

Atmospheric nitrogen and sulfur deposition is an important effect of atmospheric pollution and may affect forest ecosystems positively, for example enhancing tree growth, or negatively, for example causing acidification, eutrophication, cation depletion in soil or nutritional imbalances in trees. To assess and design measures to reduce the negative impacts of deposition, a good estimate of the deposition amount is needed, either by direct measurement or by modeling. In order to evaluate the precision of both approaches and to identify possible improvements, we compared the deposition estimates obtained using an Eulerian model with the measurements performed by two large independent networks covering most of Europe. The results are in good agreement (bias <25%) for sulfate and nitrate open field deposition, while larger differences are more evident for ammonium deposition, likely due to the greater influence of local ammonia sources. Modeled sulfur total deposition compares well with throughfall deposition measured in forest plots, while the estimate of nitrogen deposition is affected by the tree canopy. The geographical distribution of pollutant deposition and of outlier sites where model and measurements show larger differences are discussed.
An Innate Preference of Bumblebees for Volatile Organic Compounds Emitted by Phaseolus vulgaris Plants Infected With Three Different Viruses
Authors: Mhlanga Netsai Margareth , Murphy Alex M. , Wamonje Francis O. , Cunniffe Nik J. , Caulfield John C. , Glover Beverley J. , Carr John P.
Published: September 2021

Cucumber mosaic virus (CMV)-infected tomato (Solanum lycopersicum L.) plants emit volatile organic compounds (VOCs) attractive to bumblebees (Bombus terrestris L.), which are important tomato pollinators, but which do not transmit CMV. We investigated if this effect was unique to the tomato-CMV pathosystem. In two bean (Phaseolus vulgaris L.) cultivars, infection with the potyviruses bean common mosaic virus (BCMV) or bean common mosaic necrosis virus (BCMNV), or with the cucumovirus CMV induced quantitative changes in VOC emission detectable by coupled gas chromatography–mass spectrometry. In free-choice olfactometry assays bumblebees showed an innate preference for VOC blends emitted by virus-infected non-flowering bean plants and flowering CMV-infected bean plants, over VOCs emitted by non-infected plants. Bumblebees also preferred VOCs of flowering BCMV-infected plants of the Wairimu cultivar over non-infected plants, but the preference was not significant for BCMV-infected plants of the Dubbele witte cultivar. Bumblebees did not show a significant preference for VOCs from BCMNV-infected flowering bean plants but differential conditioning olfactometric assays showed that bumblebees do perceive differences between VOC blends emitted by flowering BCMNV-infected plants over non-infected plants. These results are consistent with the concept that increased pollinator attraction may be a virus-to-host payback, and show that virus-induced changes in bee-attracting VOC emission is not unique to one virus-host combination.
Single Nucleotide Polymorphisms in Apolipoprotein B, Apolipoprotein E, and Methylenetetrahydrofolate Reductase Are Associated With Serum Lipid Levels in Northern Chilean Subjects. A Pilot Study
Authors: Gálvez Anita S. , Ramírez Hugo , Placencia Pablo , Rojas Claudio , Urzúa Ximena , Kalergis Alexis M. , Salazar Luis A. , Escobar-Vera Jorge
Published: September 2021

Characterization of allelic variants is relevant to demonstrate associations among genetic background and susceptibility to develop cardiovascular diseases, which are the main cause of death in Chile. Association of APOB, APOE, and MTHFR polymorphisms with higher lipid levels and the risk of developing hypertension and cardiovascular diseases have been described. Thus, the aim of this study was to assess genotype distribution and relative allelic frequency of ApoB rs693, ApoE rs7412, ApoE rs429358, MTHFR rs1801131, and MTHFR rs1801133 allelic variants and their effects on lipid profile in young healthy men and women from Northern Chile. A group of 193 healthy subjects were enrolled for this study. Genotyping of rs693 (APOB), rs7412 and rs429358 (APOE), and rs1801131 and rs1801133 (MTHFR) polymorphisms were performed by real time PCR. In addition, lipid profiles were determined and associated to genetic data. The genotype distribution was APOB rs693 (CC = 37%, CT = 41%, and TT = 22%), APOE rs7412/rs429358 (E4 = 0.06, E3 = 0.91, and E2 = 0.03), MTHFR rs1801131 (AA = 57%, AC = 30%, and CC = 13%), and MTHFR rs1801133 (CC = 20%, CT = 47%, and TT = 33%). The association of the genetic variants with plasma lipid levels showed that women, but not men, carrying APOB mutated allele (T) and Apo E4 allele presented lower values of total cholesterol when compared with C/C homozygous genotype or E3 allele, respectively (p < 0.05). In addition, a subgroup analysis revealed that ApoB C/C homozygous women exhibited higher values of HDL-C when compared with men carrying identical genotype (p < 0.01). On the other hand, women carrying E4 allele exhibited lower values of triglycerides when compared with male carrying identical genotype (p < 0.05). Finally, women carrying mutate allele (C) for MTHFR rs1801131 showed lower levels of triglycerides when compared with A/A homozygous genotype (p < 0.05) and lower levels of LDL-C for MTHFR rs1801133 in females carrying (T) allele when compared with males carrying identical genotype (p < 0.05). In summary, the present data showed that APOB, APOE, and MTHFR single nucleotide polymorphisms are associated to lipid levels in a gender-dependent manner among healthy subjects from Northern Chile, especially in women.
Genome-Wide Association Studies in Indian Buffalo Revealed Genomic Regions for Lactation and Fertility
Authors: Vohra Vikas , Chhotaray Supriya , Gowane Gopal , Alex Rani , Mukherjee Anupama , Verma Archana , Deb Sitangsu Mohan
Published: September 2021

Murrah breed of buffalo is an excellent dairy germplasm known for its superior milk quality in terms of milk fat and solids-not-fat (SNF); however, it is often reported that Indian buffaloes had lower lactation and fertility potential compared to the non-native cattle of the country. Recent techniques, particularly the genome-wide association studies (GWAS), to identify genomic variations associated with lactation and fertility traits offer prospects for systematic improvement of buffalo. DNA samples were sequenced using the double-digestion restriction-associated DNA (RAD) tag genotyping-by-sequencing. The bioinformatics pipeline was standardized to call the variants, and single-nucleotide polymorphisms (SNPs) qualifying the stringent quality check measures were retained for GWAS. Over 38,000 SNPs were used to perform GWAS on the first two principal components of test-day records of milk yields, fat percentages, and SNF percentages, separately. GWAS was also performed on 305 days’ milk yield; lactation persistency was estimated through the rate of decline after attaining the peak yield method, along with three other standard methods; and breeding efficiency, post-partum breeding interval, and age at sexual maturity were considered fertility traits. Significant association of SNPs was observed for the first principal component, explaining the maximum proportion of variation in milk yield. Furthermore, some potential genomic regions were identified to have a potential role in regulating milk yield and fertility in Murrah. Identification of such genomic regions shall help in carrying out an early selection of high-yielding persistent Murrah buffaloes and, in the long run, would be helpful in shaping their future genetic improvement programs.
Genomic Selection and Genome-wide Association Study for Feed-Efficiency Traits in a Farmed Nile Tilapia (Oreochromis niloticus) Population
Authors: Barría Agustin , Benzie John A. H. , Houston Ross D. , De Koning Dirk-Jan , de Verdal Hugues
Published: September 2021

Nile tilapia is a key aquaculture species with one of the highest production volumes globally. Genetic improvement of feed efficiency via selective breeding is an important goal, and genomic selection may expedite this process. The aims of this study were to 1) dissect the genetic architecture of feed-efficiency traits in a Nile tilapia breeding population, 2) map the genomic regions associated with these traits and identify candidate genes, 3) evaluate the accuracy of breeding value prediction using genomic data, and 4) assess the impact of the genetic marker density on genomic prediction accuracies. Using an experimental video recording trial, feed conversion ratio (FCR), body weight gain (BWG), residual feed intake (RFI) and feed intake (FI) traits were recorded in 40 full-sibling families from the GIFT (Genetically Improved Farmed Tilapia) Nile tilapia breeding population. Fish were genotyped with a ThermoFisher Axiom 65 K Nile tilapia SNP array. Significant heritabilities, ranging from 0.12 to 0.22, were estimated for all the assessed traits using the genomic relationship matrix. A negative but favourable genetic correlation was found between BWG and the feed-efficiency related traits; −0.60 and −0.63 for FCR and RFI, respectively. While the genome-wide association analyses suggested a polygenic genetic architecture for all the measured traits, there were significant QTL identified for BWG and FI on chromosomes seven and five respectively. Candidate genes previously found to be associated with feed-efficiency traits were located in these QTL regions, including ntrk3a, ghrh and eif4e3. The accuracy of breeding value prediction using the genomic data was up to 34% higher than using pedigree records. A SNP density of approximately 5,000 SNPs was sufficient to achieve similar prediction accuracy as the full genotype data set. Our results highlight the potential of genomic selection to improve feed efficiency traits in Nile tilapia breeding programmes.
Chronic Active Antibody-Mediated Rejection Is Associated With the Upregulation of Interstitial But Not Glomerular Transcripts
Authors: Trailin Andriy , Mrazova Petra , Hruba Petra , Voska Ludek , Sticova Eva , Slavcev Antonij , Novotny Marek , Kocik Matej , Viklicky Ondrej
Published: September 2021

Molecular assessment of renal allografts has already been suggested in antibody-mediated rejection (ABMR), but little is known about the gene transcript patterns in particular renal compartments. We used laser capture microdissection coupled with quantitative RT-PCR to distinguish the transcript patterns in the glomeruli and tubulointerstitium of kidney allografts in sensitized retransplant recipients at high risk of ABMR. The expressions of 13 genes were quantified in biopsies with acute active ABMR, chronic active ABMR, acute tubular necrosis (ATN), and normal findings. The transcripts were either compartment specific (TGFB1 in the glomeruli and HAVCR1 and IGHG1 in the tubulointerstitium), ABMR specific (GNLY), or follow-up specific (CXCL10 and CX3CR1). The transcriptional profiles of early acute ABMR shared similarities with ATN. The transcripts of CXCL10 and TGFB1 increased in the glomeruli in both acute ABMR and chronic active ABMR. Chronic active ABMR was associated with the upregulation of most genes (SH2D1B, CX3CR1, IGHG1, MS4A1, C5, CD46, and TGFB1) in the tubulointerstitium. In this study, we show distinct gene expression patterns in specific renal compartments reflecting cellular infiltration observed by conventional histology. In comparison with active ABMR, chronic active ABMR is associated with increased transcripts of tubulointerstitial origin.
Superantigen Recognition and Interactions: Functions, Mechanisms and Applications
Authors: Deacy Anthony M. , Gan Samuel Ken-En , Derrick Jeremy P.
Published: September 2021

Superantigens are unconventional antigens which recognise immune receptors outside their usual recognition sites e.g. complementary determining regions (CDRs), to elicit a response within the target cell. T-cell superantigens crosslink T-cell receptors and MHC Class II molecules on antigen-presenting cells, leading to lymphocyte recruitment, induction of cytokine storms and T-cell anergy or apoptosis among many other effects. B-cell superantigens, on the other hand, bind immunoglobulins on B-cells, affecting opsonisation, IgG-mediated phagocytosis, and driving apoptosis. Here, through a review of the structural basis for recognition of immune receptors by superantigens, we show that their binding interfaces share specific physicochemical characteristics when compared with other protein-protein interaction complexes. Given that antibody-binding superantigens have been exploited extensively in industrial antibody purification, these observations could facilitate further protein engineering to optimize the use of superantigens in this and other areas of biotechnology.
System-Level Scenarios for the Elucidation of T Cell-Mediated Germinal Center B Cell Differentiation
Authors: Verstegen Niels J. M. , Ubels Victor , Westerhoff Hans V. , van Ham S. Marieke , Barberis Matteo
Published: September 2021

Germinal center (GC) reactions are vital to the correct functioning of the adaptive immune system, through formation of high affinity, class switched antibodies. GCs are transient anatomical structures in secondary lymphoid organs where specific B cells, after recognition of antigen and with T cell help, undergo class switching. Subsequently, B cells cycle between zones of proliferation and somatic hypermutation and zones where renewed antigen acquisition and T cell help allows for selection of high affinity B cells (affinity maturation). Eventually GC B cells first differentiate into long-lived memory B cells (MBC) and finally into plasma cells (PC) that partially migrate to the bone marrow to encapsulate into long-lived survival niches. The regulation of GC reactions is a highly dynamically coordinated process that occurs between various cells and molecules that change in their signals. Here, we present a system-level perspective of T cell-mediated GC B cell differentiation, presenting and discussing the experimental and computational efforts on the regulation of the GCs. We aim to integrate Systems Biology with B cell biology, to advance elucidation of the regulation of high-affinity, class switched antibody formation, thus to shed light on the delicate functioning of the adaptive immune system. Specifically, we: i) review experimental findings of internal and external factors driving various GC dynamics, such as GC initiation, maturation and GCBC fate determination; ii) draw comparisons between experimental observations and mathematical modeling investigations; and iii) discuss and reflect on current strategies of modeling efforts, to elucidate B cell behavior during the GC tract. Finally, perspectives are specifically given on to the areas where a Systems Biology approach may be useful to predict novel GCBC-T cell interaction dynamics.
Approaches to Establishing Tolerance in Immune Mediated Diseases
Authors: Huffaker Michelle F. , Sanda Srinath , Chandran Sindhu , Chung Sharon A. , St. Clair E. William , Nepom Gerald T. , Smilek Dawn E.
Published: September 2021

The development of rational approaches to restore immune tolerance requires an iterative approach that builds on past success and utilizes new mechanistic insights into immune-mediated pathologies. This article will review concepts that have evolved from the clinical trial experience of the Immune Tolerance Network, with an emphasis on lessons learned from the innovative mechanistic studies conducted for these trials and new strategies under development for induction of tolerance.
Persistence of Antibody After a Vi-Tetanus Toxoid Conjugate Vaccine and Effect of Boosting With a Plain Polysaccharide Vaccine on Vi Antibody and Antigen-Specific B Cells
Authors: Bentley Thomas , Jones Elizabeth , Jin Celina , Moore Maria , Gardner Jonathon , Hill Jennifer , Pollard Andrew J.
Published: September 2021

Background

Salmonella enterica serovar Typhi is estimated to cause 9 to 13 million cases of typhoid fever annually. Typhoid conjugate vaccines represent a promising prophylactic measure to prevent disease, but there are few data assessing persistence of immunity. The effect of a Vi polysaccharide booster vaccine in individuals previously vaccinated with the Vi-tetanus toxoid typhoid conjugate vaccine has not been assessed previously.

Methods

Thirty five healthy adult volunteers received a single dose of the Vi conjugate vaccine (Vi-TT) and 37 received a single dose of Vi polysaccharide vaccine (Vi-PS) prior to oral challenge with live S. Typhi bacteria as part of a randomised controlled, phase 2b study. In addition to data previously published showing persistence of Vi IgG and IgA antibodies for 7 months after Vi vaccination, titres were measured at intervals until 13 months post-vaccination. Ten participants who received Vi-TT (both challenged and unchallenged) were re-vaccinated with Vi-PS at an interval of 19-23 months post-prime. Anti-Vi IgG and IgA titres, and Vi-specific antibody secreting cells and memory B cells were measured at seven days and one month post-boost.

Findings

Vi IgG and IgA antibody titres remained significantly elevated above baseline levels 13 months after priming with Vi-TT, with a 4-fold rise retained in 90% and 88% of recipients (Vi IgG and IgA, respectively). Anti-Vi IgG and IgA antibody titres were found to persist at higher levels in participants who received a single dose of Vi-TT than in those who received Vi-PS. No significant boost in Vi-antibody titre was observed in response to oral challenge with S. Typhi bacteria, one month after vaccination. Following a Vi-PS booster vaccination in those previously vaccinated with Vi-TT, anti-Vi IgG and IgA titres were significantly elevated, with similar titres observed at one month post-boost compared with one month after primary vaccination. The frequency of Vi-specific IgA antibody secreting cells increased significantly 7 days post-boost compared with pre-boost. No memory B cell response was observed following Vi-PS booster vaccination.

Interpretation

Strong persistence of anti-Vi IgG and IgA following Vi-TT vaccination suggests that the conjugate vaccine may offer durable protection, supporting its use in endemic settings.
Nested Socio-Ecological Maps as a Spatial Planning Instrument for Estuary Conservation and Ecosystem-Based Management
Authors: Galván Cristina , Puente Araceli , Juanes José A.
Published: September 2021

Estuaries are socio-ecological systems that can be represented as a holistic combination of biotic and abiotic conditions in spatially explicit units defined by: (i) the ecotope, as the integration of the physiotope (abiotic-homogeneous units) and the biotope (biotic-homogeneous units), and (ii) the anthrotope, synthesizing data on human drivers of ecological change. Nested physiotopes were identified in an estuary using a hierarchical approach that integrates information about eight abiotic, and biologically meaningful, variables. The biotope of Zostera noltei was delimited using a potential distribution model of species and overlapped with the physiotope map to characterize the ecotopes. The anthrotope was estimated as the cumulative impacts of anthropic activities over the ecotopes. The diversity of Z. noltei ecotopes was compared with the anthrotope map to estimate the potential impacts of human pressures on this species. The hierarchical methodology and resulting maps provide flexible and interdisciplinary tools for conservation, management, education and research.
Quercetin Attenuates High-Fat Diet-Induced Excessive Fat Deposition of Spotted Seabass (Lateolabrax maculatus) Through the Regulatory for Mitochondria and Endoplasmic Reticulum
Authors: Dong Yan-Zou , Xia Tian , Lin Ji-Bin , Wang Ling , Song Kai , Zhang Chun-Xiao
Published: September 2021

This study aimed to investigate the effects of quercetin (QUE) on fat deposition and the underlying mechanism. Fish were fed four test diets: normal fat diet (NFD), high-fat diet (HFD), and HFD supplemented with 0.5 or 1.0 g/kg quercetin (QUE0.5 or QUE1.0). The results showed that HFD feeding resulted in poor growth and feed utilization while QUE treatment reversed this. The fat contents of serum and liver were increased by HFD and QUE supplementation significantly decreased fat content. Furthermore, gene expressions and ultrastructure observation showed that mitochondrial biogenesis and mitophagy were inhibited and endoplasmic reticulum stress (ERS) in the HFD group. QUE can activate the biogenesis and autophagy of mitochondria and suppress ERS, which is related to its fat-lowering effect.
Epidemiology and Clinical Outcomes of Microscopic Colitis: Preliminary Results From the Loyola University Microscopic Colitis Registry (LUMiCoR)
Authors: Oruganti Poornima , Awan Rehmat , Ding Xianzhong , Wesolowski Michael , Abegunde Ayokunle T.
Published: September 2021

Microscopic colitis (MC) is a common cause of chronic diarrhea with limited long-term data. We searched the pathology records at our institution from 2008 to 2018 to identify cases of MC. Total sample included patients with either a diagnosis of MC or incomplete MC (MCi).Chart review was performed and data were summarized for descriptive statistics. Logistic regression was used to estimate the unadjusted effects of predictors on MC. A total of 216 patients (88.32% white, 80.56% females, mean age 67.12 +/– 15.79) were studied; 50.00% had CC, 40.28% had LC and 9.72% had MCi. Majority (52.31%) were smokers and 21.84% of females were using some form of hormonal therapy. The odds of LC in reference to CC were significantly higher for those using tricyclic antidepressants (TCAs) (OR: 3.23, 95% C.I: 1.18–8.80, p = 0.02). The odds of smoking, statins, aspirin and beta-blocker use were decreased in MCi in reference to CC (all p < 0.05), 29 (74.35%) patients with unresolved symptoms underwent repeat colonoscopies with biopsies. One case of MCi resolved, 8 (72.73%) out of 11 cases of LC resolved, 2 (18.18%) continued to be LC and 1 (9.09%) transformed to CC, 8 (47.06%) out of 17 cases of CC resolved, 8 (47.06%) continued to be CC and 1 (5.88%) transformed to LC. Majority of patients had CC. TCA use resulted in increased odds of LC in reference to CC. Biopsies from repeat colonoscopies in some patients revealed changes in the pathological diagnoses raising the question of interchangeability of MC (CC to LC and vice versa).