bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling Inflammation in Zebrafish for the Development of Anti-inflammatory Drugs
Authors: Xie Yufei , Meijer Annemarie H. , Schaaf Marcel J. M.
Published: January 2021

Dysregulation of the inflammatory response in humans can lead to various inflammatory diseases, like asthma and rheumatoid arthritis. The innate branch of the immune system, including macrophage and neutrophil functions, plays a critical role in all inflammatory diseases. This part of the immune system is well-conserved between humans and the zebrafish, which has emerged as a powerful animal model for inflammation, because it offers the possibility to image and study inflammatory responsesin vivoat the early life stages. This review focuses on different inflammation models established in zebrafish, and how they are being used for the development of novel anti-inflammatory drugs. The most commonly used model is the tail fin amputation model, in which part of the tail fin of a zebrafish larva is clipped. This model has been used to study fundamental aspects of the inflammatory response, like the role of specific signaling pathways, the migration of leukocytes, and the interaction between different immune cells, and has also been used to screen libraries of natural compounds, approved drugs, and well-characterized pathway inhibitors. In other models the inflammation is induced by chemical treatment, such as lipopolysaccharide (LPS), leukotriene B4 (LTB4), and copper, and some chemical-induced models, such as treatment with trinitrobenzene sulfonic acid (TNBS), specifically model inflammation in the gastro-intestinal tract. Two mutant zebrafish lines, carrying a mutation in the hepatocyte growth factor activator inhibitor 1a gene (hai1a) and the cdp-diacylglycerolinositol 3-phosphatidyltransferase (cdipt) gene, show an inflammatory phenotype, and they provide interesting model systems for studying inflammation. These zebrafish inflammation models are often used to study the anti-inflammatory effects of glucocorticoids, to increase our understanding of the mechanism of action of this class of drugs and to develop novel glucocorticoid drugs. In this review, an overview is provided of the available inflammation models in zebrafish, and how they are used to unravel molecular mechanisms underlying the inflammatory response and to screen for novel anti-inflammatory drugs.
Template Assisted Generation of Chiral Luminescence in Organic Fluorophores
Authors: Maniappan Sonia , Jadhav Ashok Badrinarayan , Kumar Jatish
Published: January 2021

Development of efficient ways of fabricating chiral light emitting materials is an active area of research due to the vast potential offered by these materials in the field of optoelectronic devices, data storage, and asymmetric synthesis. Among the various methods employed, template assisted generation of chiral luminescence is gaining enormous attention due to its simplicity, applicability over a wide range of fluorescent molecules/dyes, and the display of high anisotropic values.
CLIPB10 is a Terminal Protease in the Regulatory Network That Controls Melanization in the African Malaria Mosquito Anopheles gambiae
Authors: Zhang Xin , Li Miao , El Moussawi Layla , Saab Sally , Zhang Shasha , Osta Mike A. , Michel Kristin
Published: January 2021

Humoral immune responses in animals are often tightly controlled by regulated proteolysis. This proteolysis is exerted by extracellular protease cascades, whose activation culminates in the proteolytic cleavage of key immune proteins and enzymes. A model for such immune system regulation is the melanization reaction in insects, where the activation of prophenoxidase (proPO) leads to the rapid formation of eumelanin on the surface of foreign entities such as parasites, bacteria and fungi. ProPO activation is tightly regulated by a network of so-called clip domain serine proteases, their proteolytically inactive homologs, and their serpin inhibitors. In Anopheles gambiae, the major malaria vector in sub-Saharan Africa, manipulation of this protease network affects resistance to a wide range of microorganisms, as well as host survival. However, thus far, our understanding of the molecular make-up and regulation of the protease network in mosquitoes is limited. Here, we report the function of the clip domain serine protease CLIPB10 in this network, using a combination of genetic and biochemical assays. CLIPB10 knockdown partially reversed melanotic tumor formation induced by Serpin 2 silencing in the absence of infection. CLIPB10 was also partially required for the melanization of ookinete stages of the rodent malaria parasite Plasmodium berghei in a refractory mosquito genetic background. Recombinant serpin 2 protein, a key inhibitor of the proPO activation cascade in An. gambiae, formed a SDS-stable protein complex with activated recombinant CLIPB10, and efficiently inhibited CLIPB10 activity in vitro at a stoichiometry of 1.89:1. Recombinant activated CLIPB10 increased PO activity in Manduca sexta hemolymph ex vivo, and directly activated purified M. sexta proPO in vitro. Taken together, these data identify CLIPB10 as the second protease with prophenoloxidase-activating function in An. gambiae, in addition to the previously described CLIPB9, suggesting functional redundancy in the protease network that controls melanization. In addition, our data suggest that tissue melanization and humoral melanization of parasites are at least partially mediated by the same proteases.
Prognostic Significance of End-Stage Liver Diseases, Respiratory Tract Infection, and Chronic Kidney Diseases in Symptomatic Acute Hepatitis E
Authors: Fan Huahao , Fan Junfen , Chen Suming , Chen Yangzhen , Gao Huiru , Shan Liying , Li Xue , Gu Fengjun , Zhuang Hui , Sun Lijun
Published: January 2021

Symptomatic hepatitis E virus (HEV) infection is sporadic, and usually occurs in a limited number of infected patients, which hinders the investigation of risk factors for clinical outcomes in patients with acute HEV infection. A retrospective cohort study enrolling 1913 patients with symptomatic acute hepatitis E in Beijing 302 Hospital from January 1, 2001 to December 31, 2018 was conducted. The baseline characteristics, clinical features and laboratory data of these HEV infection cases were analyzed. Albumin (ALB), platelet (PLT), alanine aminotransferase (ALT), total bilirubin (T-BiL), international normalized ratio (INR) and serum creatinine (SCR) levels, along with the model for end-stage liver disease (MELD) score, hospitalization days, co-morbidity number and mortality were taken as major parameters for comparing the clinical manifestations in our study. We found that not all pre-existing chronic liver diseases exacerbate clinical manifestations of acute hepatitis E. Alcoholic hepatitis, fatty liver hepatitis, hepatic cyst, drug-induced hepatitis and hepatocellular carcinoma were not significantly associated with mortality of HEV patients. Among all of the comorbidities, end-stage liver diseases (ESLDs, including ascites, cirrhosis, hepatic coma and hepatorenal syndrome), respiratory tract infection and chronic kidney diseases (CKDs, including renal insufficiency and renal failure) were found to remarkably increase the mortality of patients with symptomatic HEV infection. Furthermore, the severity evaluation indexes (SEI), such as MELD score, duration of hospital stay, and co-morbidity number in HEV patients with underlying comorbidities were much worse than that of their counterparts without relevant comorbidities.
P300/CBP Associated Factor (PCAF) Deficiency Enhances Diet-Induced Atherosclerosis in ApoE3*Leiden Mice via Systemic Inhibition of Regulatory T Cells
Authors: de Jong Alwin , de Jong Rob C. M. , Peters Erna A. , Arens Ramon , Jukema J. Wouter , de Vries Margreet R. , Quax Paul H. A.
Published: January 2021

Background: Inflammatory stimuli induced by NF-kB drive atherosclerotic lesion formation. The epigenetic P300/CBP associated factor (PCAF) post-transcriptionally acetylates FoxP3, which is required for regulatory T-cell (Treg) differentiation and immune modulation. We hypothesize that PCAF deficiency affects atherosclerosis via regulation of regulatory Tregs.

Method: ApoE3*Leiden (n = 13) and ApoE3*LeidenxPCAF−/− (n = 13) were fed a high-fat diet (HFD) containing 1.25% cholesterol. Systemic FoxP3+ T cells were measured every 4 weeks by flow cytometry (n = 6). After 5-months of HFD, mice were euthanized, and hearts and blood were collected. IL-6 and TNFα concentrations were measured in plasma to identify systemic inflammatory responses. Compositional and morphometrical analyses were performed on the atherosclerotic lesions in the aortic sinuses.

Results: After 5 months of HFD, plasma cholesterol concentrations were not different for ApoE3*LeidenxPCAF−/− compared to ApoE3*Leiden mice. Expression of FoxP3 by systemic CD4+ T cells decreased 1.8 fold in ApoE3*LeidenxPCAF−/− after 5 months HFD and remained significantly reduced after 5 months of HFD. Systemic TNFα and IL-6 concentrations were comparable, whereas the atherosclerotic lesion size in ApoE3*LeidenxPCAF−/− mice was increased by 28% compared to ApoE3*Leiden mice. In atherosclerotic lesions, no differences were observed in macrophage differentiation or VSMC content, although a small increase in collagen was identified.

Conclusion: Our data show that PCAF deficiency resulted in a decrease in circulatory FoxP3+ regulatory T cells and ameliorated atherosclerotic lesions with no differences in systemic inflammation or macrophage differentiation in the atherosclerotic lesions. This suggests that PCAF regulates atherosclerosis via modulation of FoxP3+ regulatory T cell differentiation.
Deleterious Effects of Epicardial Adipose Tissue Volume on Global Longitudinal Strain in Patients With Preserved Left Ventricular Ejection Fraction
Authors: Maimaituxun Gulinu , Kusunose Kenya , Yamada Hirotsugu , Fukuda Daiju , Yagi Shusuke , Torii Yuta , Yamada Nao , Soeki Takeshi , Masuzaki Hiroaki , Sata Masataka , Shimabukuro Michio
Published: January 2021

Background: It is known that epicardial adipose tissue (EAT) volume is linked to cardiac dysfunction. However, it is unclear whether EAT volume (EATV) is closely linked to abnormal LV strain. We examined the relationship between EATV and global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) in patients with preserved LV function.

Methods: Notably, 180 consecutive subjects (68 ± 12 years; 53% men) underwent 320-slice multi-detector computed tomography coronary angiography and were segregated into coronary artery disease (CAD) (≥1 coronary artery branch stenosis ≥50%) and non-CAD groups. GLS, GCS, and GRS were evaluated by 2-dimensional speckle tracking in patients with preserved left ventricular (LV) ejection fraction (LVEF) ≥50%.

Results: First, GLS, but not GRS and GCS, was lower in the high EATV group though the LVEF was comparable to the low EATV group. Frequency of GLS ≤18 was higher in the high EATV group. Second, multiple regression model showed that EATV, age, male sex, and CAD, were determinants of GLS. Third, the cutoff points of EATV were comparable (~116–117 mL) in both groups. The cutoff of EATV ≥116 showed a significant correlation with GLS ≤18 in overall subjects.

Conclusions: Increasing EATV was independently associated with global longitudinal strain despite the preserved LVEF and lacking obstructive CAD. Our findings suggest an additional role of EAT on myocardial systolic function by impaired LV longitudinal strain.
Case Report: Thromboembolism and Hemorrhagic Pericardial Effusion—The Janus Face of Primary Pericardial Angiosarcoma
Authors: Chen Fei F. , Jiang Shu F. , Dong Chang , Che Ying , Du Lin Y. , Li Zhi Y. , Yang Zhi Q. , Zhao Yi C. , Liu Ying
Published: January 2021

Background: Primary cardiac angiosarcomas, especially those originating in the pericardium, are extremely rare and aggressive tumors with poor prognosis. These types of malignant tumors have diverse clinical presentations and are often masked by other comorbidities.

Case Summary: Our hospital reported a 59-year-old woman who initially presented with pulmonary thromboembolism (PTE) and was subsequently treated with low-molecular-weight heparin. However, she experienced acute pericardial tamponade after anticoagulation therapy, where no obvious mass was primarily identified upon imaging, both in the pericardium or within the heart. Emergency pericardiocentesis and drainage were performed, where a total of 210 mL of bloody effusion was drained. Four months later, she was hospitalized with progressive hemoptysis and dyspnea. A large mixed mass occupying the right pericardium was later identified by coronary computed tomography angiography (CCTA). The mass was consistent with the right atrium, with heterogeneous thickened pericardium and localized moderate pericardial effusion. CCTA and positron emission tomography scans later showed metastases in both lungs and bilateral pleura. Nodules in hilar and mediastinal lymph nodes were also significant. Ultrasound-guided biopsy was performed, and the patient was ultimately diagnosed with an angiosarcoma based on final positive results for both CD31 and CD34 markers. The patient refused chemotherapy and passed away while waiting for her pathology results. The patient survived for 6 months since the first reported episode of PTE.

Conclusions: Our case indicates that patients presenting with both embolism and hemorrhage should urgently be channeled to a clinical specialist to confirm any malignant etiology. This would be beneficial to confirm an early diagnosis and lengthen the duration of patient survival. However, the diagnosis of primary cardiac angiosarcoma is still challenging and requires multiple imaging modalities and biopsies in order to assist the accurate diagnosis of disease and achieve effective patient management.
Case Report: Multi-Modality Imaging of a Right Atrial Pseudoaneurysm in a Patient With Breast Cancer
Authors: Zhong Ying , Ma Chun-yan , Dai Xu , Wang Guan
Published: January 2021

Cardiac pseudoaneurysms occur when a blood vessel wall is injured and the leaking blood is collected in the surrounding tissue. They are very rare events and have a high risk of rupture and poor prognosis. We report a case of right atrial pseudoaneurysm in a 54-year-old female patient diagnosed with breast cancer and lung metastasis. The patient underwent five intrapericardial infusions of cisplatin and nine cycles of systemic chemotherapy. Non-contrast-enhanced computed tomography (CT) was performed at follow-up evaluation during the chemotherapeutic process as this patient was contraindicated to iodine. CT without contrast and ultrasonography showed a crescent-shaped lesion near the right atrium but its nature could not be determined. Cardiac magnetic resonance (CMR) imaging with gadolinium contrast provided important information as an alternative enhanced imaging modality. By combining CT, ultrasonography and CMR images with the medical history of the patient, we inferred that the lesion was a pseudoaneurysm in the right atrium. This condition was related to the erosion of metastasized tumor cells or the accumulated cardiac toxicity of multiple cycles of chemotherapy or pericardiocentesis. This single case report suggests that cardiac rupture should be considered as a potential complication in patients with suspected pericardial metastasis. CMR imaging is an excellent tool for the detection of right atrial rupture.
Hydrological Analysis of Loess Plateau Highland Control Schemes in Dongzhi Plateau
Authors: Huo Aidi , Peng Jianbing , Cheng Yuxiang , Luo Pingping , Zhao Zhixin , Zheng Chunli
Published: January 2021

Gully Consolidation and Highland Protection (GCHP) Project is a major soil and water conservation and land remediation project implemented in the Chinese Loess Plateau (CLP). As the connection between the mechanisms of erosion and practical applications for addressing it is not clear, the implementation of engineering measures to combat the problem has been insufficient to date. This study used field investigation and descriptive statistics, together with hydrological analysis modeling to gain an understanding of the impact of the Loess Plateau Highland Control Schemes on the evolution of the Dongzhi Plateau as the largest, most well-preserved, and the thickest loess deposit region in China. A remote sensing image was introduced to hydrological modeling to prove the analysis results of the Dongzhi Plateau. According to these investigations and analysis, four major schemes of gully head retrogressive erosion control were summarized and a comprehensive theory and technology based on a watershed were proposed. After hydrological analysis, the Dongzhi Plateau was divided into 1225 watersheds. It was found that GCHP should be implemented in the catchment area based on hydrological analysis to solve the problem of retrogressive erosion, and it is recommended that a scientific and rational drainage system should be designed based on the roads and pipe networks in the whole watershed area. Findings from this paper provide insights into the evolution of CLP and it can give a good suggestion on the future implementation of GHCP.
Modelling the Effects of Non-Steady State Transport Dynamics on the Sulfur and Oxygen Isotope Composition of Sulfate in Sedimentary Pore Fluids
Authors: Fotherby Angus , Bradbury Harold J. , Antler Gilad , Sun Xiaole , Druhan Jennifer L. , Turchyn Alexandra V.
Published: January 2021

We present the results of an isotope-enabled reactive transport model of a sediment column undergoing active microbial sulfate reduction to explore the response of the sulfur and oxygen isotopic composition of sulfate under perturbations to steady state. In particular, we test how perturbations to steady state influence the cross plot of δ34S and δ18O for sulfate. The slope of the apparent linear phase (SALP) in the cross plot of δ34S and δ18O for sulfate has been used to infer the mechanism, or metabolic rate, of microbial metabolism, making it important that we understand how transient changes might influence this slope. Tested perturbations include changes in boundary conditions and changes in the rate of microbial sulfate reduction in the sediment. Our results suggest that perturbations to steady state influence the pore fluid concentration of sulfate and the δ34S and δ18O of sulfate but have a minimal effect on SALP. Furthermore, we demonstrate that a constant advective flux in the sediment column has no measurable effect on SALP. We conclude that changes in the SALP after a perturbation are not analytically resolvable after the first 5% of the total equilibration time. This suggests that in sedimentary environments the SALP can be interpreted in terms of microbial metabolism and not in terms of environmental parameters.
Case Study on Geoscience Teaching Innovation: Using 3D Printing to Develop Structural Interpretation Skill in Higher Education Levels
Authors: Chenrai Piyaphong
Published: January 2021

Applying three-dimensional (3D) printing technology to a geoscience classroom provides an alternative way to teach students. This brief report describes an educational innovation for the geoscience classroom by 3D printing technology to develop structural interpretation skill in high education level in Thailand. In comparison to traditional classrooms, this teaching method enables students to more easily comprehend how geological structures and features occur in nature through a project-based learning in seismic interpretation course. 3D printing models are constructed based on student interpretation through three different software packages. The observations in this study indicate that the ability to create the 3D models based on digital seismic data can enhance structural interpretation skill of students. The benefit of freely orientating and viewing in different angles of the 3D models leads to a construction of cognitive abstract space and spatial visualization ability. Therefore, 3D printing technology plays an important role in changing and developing the geoscience education system in Thailand at present and in the future. This teaching method could potentially benefit any science classroom and have applications in other disciplines requiring similar skill.
Association Between Vitamin D and Resistin in Postmenopausal Females With Altered Bone Health
Authors: Tariq Sundus , Tariq Saba , Khaliq Saba , Baig Mukhtiar , Murad Manal Abdulaziz , Lone Khalid Parvez
Published: January 2021

Background

Resistin is a relatively novel adipokine that has a role in bone remodeling and may regulate bone mineral density (BMD). Vitamin D and adipokines have a dynamic role in the body’s various metabolic processes, including bone metabolism, and may alter bone metabolism in relation to each other. This study aimed to investigate the association between vitamin D and serum resistin levels in postmenopausal non-osteoporotic and osteoporotic females.

Methods

This correlational analytical study was conducted on 161 postmenopausal females, divided into two groups, non-osteoporotic and osteoporotic, between 50–70 years. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DXA) scan. Serum resistin and vitamin D levels were analyzed by enzyme-linked immunosorbent assay (ELISA) method. Serum calcium, phosphate, and alkaline phosphatase with spectrophotometry. A correlation was checked using spearman’s rho correlation coefficient, and multivariate stepwise regression analysis was used to predict serum resistin levels.

Results

Postmenopausal females (n=161) having sufficient, insufficient and deficient levels of vitamin D were 87 (54.0%), 64 (39.8%), and 10 (6.2%), respectively. Lumbar spine BMD (p < 0.001), total hip BMD (p < 0.001), and serum resistin levels (p < 0.001) were significantly different between the two groups. There was a significant negative correlation between serum resistin and vitamin D in postmenopausal females (rho = -0.182, p = 0.021) and osteoporotic group (rho = -0.253, p = 0.019) but non-significant in non-osteoporotic group (rho = -0.077, p = 0.509). Serum vitamin D was found to be independent predictor of serum resistin levels, accounting for only 3% variance.

Conclusion

Serum vitamin D levels were low while serum resistin levels were high in postmenopausal osteoporotic females and vitamin D is a negative predictor of serum resistin levels.
Design of Genetic Programming Control Algorithm for Low-Temperature PEM Fuel Cell
Authors: Haddad Abdel Gafoor , Al-Durra Ahmed , Boiko Igor
Published: January 2021

An effective control system for the air supply in fuel cell systems (FCS) is required to prevent oxygen starvation and to maximize the net power. For this purpose, conventional feedback and adaptive controllers are designed using genetic programming (GP). To minimize the time required for the GP convergence, FCS models of different complexity are studied and a comparison between them is carried out. Guidelines on applying the GP approach based on data obtained from simulations are developed along with a specially designed cost function that promotes closed-loop linearization. The advantage of this design method lies in its applicability to complex nonlinear systems for which nonlinear control methods may not be applicable. Adaptation is added to the oxygen excess ratio (OER) regulation problem by training a neural network that provides the optimal OER reference based on the stack current and temperature. The performance of both the regulation and adaptive controllers is tested under noise in the compressor flow and the stack current measurements. The robustness of the GP controllers is observed through the frequency response analysis.
Standards and Best Practices for Monitoring and Benchmarking Insects
Authors: Montgomery Graham A. , Belitz Michael W. , Guralnick Rob P. , Tingley Morgan W.
Published: January 2021

Benchmark studies of insect populations are increasingly relevant and needed amid accelerating concern about insect trends in the Anthropocene. The growing recognition that insect populations may be in decline has given rise to a renewed call for insect population monitoring by scientists, and a desire from the broader public to participate in insect surveys. However, due to the immense diversity of insects and a vast assortment of data collection methods, there is a general lack of standardization in insect monitoring methods, such that a sudden and unplanned expansion of data collection may fail to meet its ecological potential or conservation needs without a coordinated focus on standards and best practices. To begin to address this problem, we provide simple guidelines for maximizing return on proven inventory methods that will provide insect benchmarking data suitable for a variety of ecological responses, including occurrence and distribution, phenology, abundance and biomass, and diversity and species composition. To track these responses, we present seven primary insect sampling methods—malaise trapping, light trapping, pan trapping, pitfall trappings, beating sheets, acoustic monitoring, and active visual surveys—and recommend standards while highlighting examples of model programs. For each method, we discuss key topics such as recommended spatial and temporal scales of sampling, important metadata to track, and degree of replication needed to produce rigorous estimates of ecological responses. We additionally suggest protocols for scalable insect monitoring, from backyards to national parks. Overall, we aim to compile a resource that can be used by diverse individuals and organizations seeking to initiate or improve insect monitoring programs in this era of rapid change.
From Bees to Flies: Global Shift in Pollinator Communities Along Elevation Gradients
Authors: McCabe Lindsie M. , Cobb Neil S.
Published: January 2021

Bees decrease in abundance and richness along elevation gradients, while flies replace bees as the dominant flower visitors in higher elevation systems. We reviewed the existing literature to determine if this global phenomenon of pollinator communities switching from bees to flies occurs at the same place along a temperature gradient. Here we examined five studies that have documented this bee-to-fly transition in the North America, South America, Europe & Australia. We determined where the bee-to-fly transition occurred along a temperature/elevation gradient for each study that ranged from 1.1 to 8.3°C. We found that pollinator communities shifted from bee dominated to fly dominated communities between 4.9 and 5.7°C on all elevation gradients worldwide. This shift in pollinators could substantially impact ecological systems reliant on fly pollination as temperatures continue to warm.
Hierarchical Modelling of Haplotype Effects on a Phylogeny
Authors: Selle Maria Lie , Steinsland Ingelin , Lindgren Finn , Brajkovic Vladimir , Cubric-Curik Vlatka , Gorjanc Gregor
Published: January 2021

We introduce a hierarchical model to estimate haplotype effects based on phylogenetic relationships between haplotypes and their association with observed phenotypes. In a population there are many, but not all possible, distinct haplotypes and few observations per haplotype. Further, haplotype frequencies tend to vary substantially. Such data structure challenge estimation of haplotype effects. However, haplotypes often differ only due to few mutations, and leveraging similarities can improve the estimation of effects. We build on extensive literature and develop an autoregressive model of order one that models haplotype effects by leveraging phylogenetic relationships described with a directed acyclic graph. The phylogenetic relationships can be either in a form of a tree or a network, and we refer to the model as the haplotype network model. The model can be included as a component in a phenotype model to estimate associations between haplotypes and phenotypes. Our key contribution is that we obtain a sparse model, and by using hierarchical autoregression, the flow of information between similar haplotypes is estimated from the data. A simulation study shows that the hierarchical model can improve estimates of haplotype effects compared to an independent haplotype model, especially with few observations for a specific haplotype. We also compared it to a mutation model and observed comparable performance, though the haplotype model has the potential to capture background specific effects. We demonstrate the model with a study of mitochondrial haplotype effects on milk yield in cattle. We provide R code to fit the model with the INLA package.
Single-Nucleotide Polymorphism Variations Associated With Specific Genes Putatively Identified Enhanced Genetic Predisposition for 305-Day Milk Yield in the Girolando Crossbreed
Authors: da Cruz Alex Silva , Silva Danilo Conrado , Minasi Lysa Bernardes , de Farias Teixeira Larissa Kamídia , Rodrigues Flávia Melo , da Silva Claudio Carlos , do Carmo Adriana Santana , da Silva Marcos Vinicius Gualberto Barbosa , Utsunomiya Yuri Tani , Garcia José Fernando , da Cruz Aparecido Divino
Published: January 2021

Milk production phenotypes are the main focus of genetic selection in dairy herds, and although there are many genes identified as related to the biology of these traits in pure breeds, little is known about crossbreed animals. This study aimed to identify potential genes associated with the 305-day milk yield in 337 crossbreed Gir × Holstein (Girolando) animals. Milk production records were genotyped for 45,613 single-nucleotide polymorphisms (SNPs). This dataset was used for a genome-wide association study (GWAS) using the 305-day milk yield adjusted for the fixed effects of herd and year and linear and quadratic effects of age at calving (in days) and calving factor averaged per animal. Genes within the significant SNPs were retrieved from the Bos taurus ARS-UCD1.2 assembly (bosTau9) for gene ontology analysis. In summary, the GWAS identified 52 SNPs associated [p ≤ 10–4, false discovery rate (FDR) = 8.77%] with milk production, including NUB1 and SLC24A2, which were previously described as related to milk production traits in cattle. The results suggest that SNPs associated mainly with NUB1 and SLC24A2 could be useful to understand milk production in Girolando and used as predictive markers for selecting genetic predisposition for milk yield in Girolando.
Clopidogrel Resistance Is Associated With DNA Methylation of Genes From Whole Blood of Humans
Authors: Yang Jin , Yu Qinglin , Xu Zhifeng , Zheng Nan , Zhong Jinyan , Li Jiyi , Liu Yahui , Xu Hongyu , Su Jia , Ji Lindan , Chen Xiaomin
Published: January 2021

Antiplatelet therapy has become a cornerstone in the treatment of coronary heart disease (CHD). However, due to high-residual-platelet-reactivity, clopidogrel resistance (CR) is a common phenomenon, and it is rarely known about the relationship between CR and epigenetic changes. This study compared the whole genomic methylation patterns of blood samples from patients with CR (n = 6) and non-CR (n = 6) with the Human Methylation 850K BeadChip assay. We explored differentially methylated CpG sites, genes, and pathways using bioinformatics profiling. The CR and control groups showed significantly different DNA methylation at 7,098 sites, with 979 sites showing hypermethylation and 6,119 sites showing hypomethylation. The pyrosequencing method was used to validate four differentially methylated CpG loci (cg23371584, cg15971518, cg04481923, cg22507406), confirming that DNA methylation was associated with the risk of CR (30 CR vs. 30 non-CR). The relative mRNA expression of the four genes (BTG2, PRG2, VTRNA2-1, PER3) corresponding to the loci above was also associated with CR, suggesting that alterations in DNA methylation may affect the expression of these four genes, eventually resulting in CR. Additionally, differentially methylated sites are partially related to genes and pathways that play key roles in process of circadian entrainment, insulin secretion, and so on. Hence, the mechanism and biological regulation of CR might be reflected through these epigenetic alterations, but future research will need to address the causal relationships.
Significant Differences in Host-Pathogen Interactions Between Murine and Human Whole Blood
Authors: Machata Silke , Sreekantapuram Sravya , Hünniger Kerstin , Kurzai Oliver , Dunker Christine , Schubert Katja , Krüger Wibke , Schulze-Richter Bianca , Speth Cornelia , Rambach Günter , Jacobsen Ilse D.
Published: January 2021

Murine infection models are widely used to study systemic candidiasis caused byC. albicans. Whole-blood models can help to elucidate host-pathogens interactions and have been used for severalCandidaspecies in human blood. We adapted the human whole-blood model to murine blood. Unlike human blood, murine blood was unable to reduce fungal burden and more substantial filamentation ofC. albicanswas observed. This coincided with less fungal association with leukocytes, especially neutrophils. The lower neutrophil number in murine blood only partially explains insufficient infection and filamentation control, as spiking with murine neutrophils had only limited effects on fungal killing. Furthermore, increased fungal survival is not mediated by enhanced filamentation, as a filament-deficient mutant was likewise not eliminated. We also observed host-dependent differences for interaction of platelets withC. albicans, showing enhanced platelet aggregation, adhesion and activation in murine blood. For human blood, opsonization was shown to decrease platelet interaction suggesting that complement factors interfere with fungus-to-platelet binding. Our results reveal substantial differences between murine and human whole-blood models infected withC. albicansand thereby demonstrate limitations in the translatability of thisex vivomodel between hosts.
A Longitudinal Analysis Reveals Early Activation and Late Alterations in B Cells During Primary HIV Infection in Mozambican Adults
Authors: Jiménez Montse , Pastor Lucía , Urrea Victor , Rodríguez de la Concepción María Luisa , Parker Erica , Fuente-Soro Laura , Jairoce Chenjerai , Mandomando Inacio , Carrillo Jorge , Naniche Denise , Blanco Julià
Published: January 2021

Primary HIV infection (PHI) and subsequent chronic infection alter B-cell compartment. However, longitudinal analysis defining the dynamics of B-cell alterations are still limited. We longitudinally studied B-cell subsets in individuals followed for 1 year after PHI (n = 40). Treated and untreated chronic HIV infected (n = 56) and HIV-uninfected individuals (n = 58) were recruited as reference groups at the Manhiça District in Mozambique. B cells were analyzed by multicolor flow-cytometry. Anti-HIV humoral response and plasma cytokines were assessed by ELISA or Luminex-based technology. A generalized activation of B cells induced by HIV occurs early after infection and is characterized by increases in Activated and Tissue-like memory cells, decreases in IgM-IgD- (switched) and IgM-only B cells. These alterations remain mostly stable until chronic infection and are reverted in part by ART. In contrast, other parameters followed particular dynamics: PD-1 expression in memory cells decreases progressively during the first year of infection, Transitional B cells expand at month 3–4 after infection, and Marginal zone-like B cells show a late depletion. Plasmablasts expand 2 months after infection linked to plasma viral load and anti-p24 IgG3 responses. Most of well-defined changes induced by HIV in B-cell activation and memory subsets are readily observed after PHI, lasting until ART initiation. However, subsequent changes occur after sustained viral infection. These data indicate that HIV infection impacts B cells in several waves over time, and highlight that early treatment would result in beneficial effects on the B-cell compartment.
Materials and Methods of Biosensor Interfaces With Stability
Authors: Song Min , Lin Xiaogang , Peng Zhijia , Xu Shibin , Jin Lifeng , Zheng Xiaodong , Luo Haoyue
Published: January 2021

Biosensors can convert the concentration of biological analytes into an electrical signal or other signals for detection. They are widely used in medical diagnostics, food safety, process control, and environmental monitoring fields. In recent years, new schemes of stable biosensor interfaces have attracted much attention. Interface design is a vital part of biosensor development, since its stability can be directly related to the quality of sensing performance such as sensitivity, stability, and linearity. This review summarized the latest methods and materials used to construct stable biosensor interfaces and pointed some future perspectives and challenges of them. From the literature, we found that nanomaterials, polymers, and their composites such as chitosan, cellulose, and conducting polymers are the most common materials used in the biosensor interface design. Apart from materials, there are increasing developments in monolayer membrane techniques, three-dimensional constructions, and other interface techniques. This review is a study of the latest progress in biosensor interface stability solutions, which may provide some references and innovative directions of biosensor interface design for researchers in biosensor fields and encourage people to further explore new materials and methods.
Study Protocol of the PreFiPS Study: Prevention of Postoperative Pancreatic Fistula by Somatostatin Compared With Octreotide, a Prospective Randomized Controlled Trial
Authors: Hain Elisabeth , Challine Alexandre , Tzedakis Stylianos , Mare Alexandru , Martinino Alessandro , Fuks David , Adham Mustapha , Piessen Guillaume , Regimbeau Jean-Marc , Buc Emmanuel , Barbier Louise , Vaillant Jean-Christophe , Jeune Florence , Sulpice Laurent , Muscari Fabrice , Schwarz Lilian , Deguelte Sophie , Sa Cunha Antonio , Truant Stephanie , Dousset Bertrand , Sauvanet Alain , Gaujoux Sébastien
Published: January 2021

Background: Pancreatic fistula (PF), i. e., a failure of the pancreatic anastomosis or closure of the remnant pancreas after distal pancreatectomy, is one of the most feared complications after pancreatic surgery. PF is also one of the most common complications after pancreatic surgery, occurring in about 30% of patients. Prevention of a PF is still a major challenge for surgeons, and various technical and pharmacological interventions have been investigated, with conflicting results. Pancreatic exocrine secretion has been proposed as one of the mechanisms by which PF occurs. Pharmacological prevention using somatostatin or its analogs to inhibit pancreatic exocrine secretion has shown promising results. We can hypothesize that continuous intravenous infusion of somatostatin-14, the natural peptide hormone, associated with 10–50 times stronger affinity with all somatostatin receptor compared with somatostatin analogs, will be associated with an improved PF prevention.

Methods: A French comparative randomized open multicentric study comparing somatostatin vs. octreotide in adult patients undergoing pancreaticoduodenectomy (PD) or distal pancreatectomy with or without splenectomy. Patients with neoadjuvant radiation therapy and/or neoadjuvant chemotherapy within 4 weeks before surgery are excluded from the study. The main objective of this study is to compare 90-day grade B or C postoperative PF as defined by the last ISGPF (International Study Group on Pancreatic Fistula) classification between patients who receive perioperative somatostatin and octreotide. In addition, we analyze overall length of stay, readmission rate, cost-effectiveness, and postoperative quality of life after pancreatic surgery in patients undergoing PD.

Conclusion: The PreFiPS study aims to evaluate somatostatin vs. octreotide for the prevention of postoperative PF.
Acetylation of Response Regulator Protein MtrA in M. tuberculosis Regulates Its Repressor Activity
Authors: Singh Krishna Kumar , Athira P. J. , Bhardwaj Neerupma , Singh Devendra Pratap , Watson Uchenna , Saini Deepak Kumar
Published: January 2021

MtrA is an essential response regulator (RR) protein in M. tuberculosis, and its activity is modulated after phosphorylation from its sensor kinase MtrB. Interestingly, many regulatory effects of MtrA have been reported to be independent of its phosphorylation, thereby suggesting alternate mechanisms of regulation of the MtrAB two-component system in M. tuberculosis. Here, we show that RR MtrA undergoes non-enzymatic acetylation through acetyl phosphate, modulating its activities independent of its phosphorylation status. Acetylated MtrA shows increased phosphorylation and enhanced interaction with SK MtrB assessed by phosphotransfer assays and FRET analysis. We also observed that acetylated MtrA loses its DNA-binding ability on gene targets that are otherwise enhanced by phosphorylation. More interestingly, acetylation is the dominant post-translational modification, overriding the effect of phosphorylation. Evaluation of the impact of MtrA and its lysine mutant overexpression on the growth of H37Ra bacteria under different conditions along with the infection studies on alveolar epithelial cells further strengthens the importance of acetylated MtrA protein in regulating the growth of M. tuberculosis. Overall, we show that both acetylation and phosphorylation regulate the activities of RR MtrA on different target genomic regions. We propose here that, although phosphorylation-dependent binding of MtrA drives its repressor activity on oriC and rpf, acetylation of MtrA turns this off and facilitates division in mycobacteria. Our findings, thus, reveal a more complex regulatory role of RR proteins in which multiple post-translational modifications regulate the activities at the levels of interaction with SK and the target gene expression.
Presence and Characterization of a Novel cfr-Carrying Tn558 Transposon Derivative in Staphylococcus delphini Isolated From Retail Food
Authors: Zhang Feng , Wu Shi , Huang Jiahui , Yang Runshi , Zhang Jumei , Lei Tao , Dai Jingsha , Ding Yu , Xue Liang , Wang Juan , Chen Moutong , Wu Qingping
Published: January 2021

Antimicrobial resistance has become a major public health threat. Food-related Staphylococcus species have received much attention due to their multidrug resistance. The cfr gene associated with multidrug resistance has been consistently detected in food-derived Staphylococcus species. In this retrospective study, we examined the prevalence of cfr-positive Staphylococcus strains isolated from poultry meat in different geographical areas of China from 2011 to 2016. Two cfr-positive Staphylococcus delphini strains were identified from poultry meat in China. Comparative and whole-genome analyses were performed to characterize the genetic features and overall antimicrobial resistance genes in the two S. delphini isolates 245-1 and 2794-1. Whole-genome sequencing showed that they both harbored a novel 20,258-bp cfr-carrying Tn558 transposon derivative on their chromosomes. The Tn558 derivative harbors multiple antimicrobial resistance genes, including the transferable multiresistance gene cfr, chloramphenicol resistance gene fexA, aminoglycoside resistance genes aacA-aphD and aadD, and bleomycin resistance gene ble. Surprisingly, within the Tn558 derivative, an active unconventional circularizable structure containing various resistance genes and a copy of a direct repeat sequence was identified by two-step PCR. Furthermore, core genome phylogenetic analysis revealed that the cfr-positive S. delphini strains were most closely related to S. delphini 14S03313-1 isolated from Japan in 2017 and 14S03319-1 isolated from Switzerland in 2017. This study is the first report of S. delphini harboring a novel cfr-carrying Tn558 derivative isolated from retail food. This finding raises further concerns regarding the potential threat to food safety and public health safety. The occurrence and dissemination of similar cfr-carrying transposons from diverse Staphylococcus species need further surveillance.
Metagenomics-Based Approach to Source-Attribution of Antimicrobial Resistance Determinants – Identification of Reservoir Resistome Signatures
Authors: Duarte Ana Sofia Ribeiro , Röder Timo , Van Gompel Liese , Petersen Thomas Nordahl , Hansen Rasmus Borup , Hansen Inge Marianne , Bossers Alex , Aarestrup Frank M. , Wagenaar Jaap A. , Hald Tine
Published: January 2021

Metagenomics can unveil the genetic content of the total microbiota in different environments, such as food products and the guts of humans and livestock. It is therefore considered of great potential to investigate the transmission of foodborne hazards as part of source-attribution studies. Source-attribution of antimicrobial resistance (AMR) has traditionally relied on pathogen isolation, while metagenomics allows investigating the full span of AMR determinants. In this study, we hypothesized that the relative abundance of fecal resistome components can be associated with specific reservoirs, and that resistomes can be used for AMR source-attribution. We used shotgun-sequences from fecal samples of pigs, broilers, turkeys- and veal calves collected across Europe, and fecal samples from humans occupationally exposed to livestock in one country (pig slaughterhouse workers, pig and broiler farmers). We applied both hierarchical and flat forms of the supervised classification ensemble algorithm Random Forests to classify resistomes into corresponding reservoir classes. We identified country-specific and -independent AMR determinants, and assessed the impact of country-specific determinants when attributing AMR resistance in humans. Additionally, we performed a similarity percentage analysis with the full spectrum of AMR determinants to identify resistome signatures for the different reservoirs. We showed that the number of AMR determinants necessary to attribute a resistome into the correct reservoir increases with a larger reservoir heterogeneity, and that the impact of country-specific resistome signatures on prediction varies between countries. We predicted a higher occupational exposure to AMR determinants among workers exposed to pigs than among those exposed to broilers. Additionally, results suggested that AMR exposure on pig farms was higher than in pig slaughterhouses. Human resistomes were more similar to pig and veal calves’ resistomes than to those of broilers and turkeys, and the majority of these resistome dissimilarities can be explained by a small set of AMR determinants. We identified resistome signatures for each individual reservoir, which include AMR determinants significantly associated with on-farm antimicrobial use. We attributed human resistomes to different livestock reservoirs using Random Forests, which allowed identifying pigs as a potential source of AMR in humans. This study thus demonstrates that it is possible to apply metagenomics in AMR source-attribution.