bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of soil humidity dynamics under grain wheat crops
Authors:   Khmelnytsky National University, Oleksandrenko V. , Kurskoi V. ,   Khmelnytsky National University, Davydenko G. ,   Sumy National Agrarian University, Solarov O. ,   Sumy National Agrarian University
Published: November 2020

One of the most important factors for the development of modern agricultural entrepreneurship is the stable and productive conduct of agricultural production. The main purpose of the article is to study the rate of moisture release after harvesting winter crops and to find the optimal sowing time after harvest. All studies were conducted in real production conditions in accordance with the developed research methodology. Modern devices of different types were used to obtain the most reliable values. An important factor for obtaining high yields is the full disclosure of the potential of available moisture and air in the upper fertile layer of the soil. Gradual movement of climatic zones to the north of Ukraine requires the study of the rate of moisture release from the soil and the determination of the most optimal terms for sowing. In a fairly dry period, the beginning of sowing of winter cereals is necessary immediately after harvest at soil moisture – 17-22 %. All necessary agricultural measures to prepare the soil in summer for winter crops (background and main tillage) should be carried out taking into account the basic principles of the theory of "differentiated humidity", according to which the main amount of soil moisture in the range of GWP (marginal field moisture content) is lost due to the upward movement of water through macro- and micro-wells. One of the methods to reduce moisture loss is to create a loose layer on the soil surface, which prevents capillary leakage of moisture and acts as mulch. The loose layer itself significantly slows down the heating of the surface and interrupts the flow of moisture to the evaporation horizon, so it is recommended immediately after harvest to remove straw from the field for loosening the top layer of soil. Significantly reduce the drying of the soil gives some compaction of the soil in its upper layer, which reduces the loss of steam, by moving balers and bales of straw on the surface of the field.
Bioeconomic advantages of developing enterprises operating in dairy products industry
Authors:   Polissia National University, Bugaychuk V. , Opalov О. ,   Polissia National University, Grabchuk І. ,   Polissia National University, Razumna К. ,   Polissia National University
Published: November 2020

Currently, there is a global trend to produce a variety of products, goods and energy using renewable organic raw materials based on the widespread application of biotechnology. That is, the bioeconomy creates bioeconomic advantages in the interaction between the economy, environment, technology and society due to the fact that it uses scientific and technological innovations that act as drivers. For PJSC Zhytomyr Butter Plant such measures are priority areas in production, organizational and technical activities. In particular, the new line “Straightline SL1100 F2 from Tetra Pak” will make it possible to reduce the production cost of 1 ton of ice cream and improve its quality. According to the enterprise’s estimates, in 2020 the sales turnover will be 51,840.0 thousand items; the unit cost will be UAH 30. As a result, the revenue will be UAH 1,554.0 thousand. Over the years, sales turnover and price will increase, so sales revenue will also increase and will amount to UAH 1,631.2 in 2021, UAH 1,675.6 in 2022, UAH 1,703.3 in 2023. The amount of profit will grow annually in the range from 6.4 % to 9.0 %. Thus, the enterprise can create bioeconomic advantages through high quality products, lower production costs, and most importantly, through the development of key competencies that create unique value for consumers.
Personnel and intellectual component of economic security of the agricultural sector: essence and meaning
Authors:   Kharkiv National Agrarian University named after  V. V. Dokuchaiev, Utenkova K.
Published: November 2020

The economic security of the agricultural sector is related to the economic security of the state and the economic security of individual enterprises operating in this sector of the economy. The important component of economic security of agricultural sector is personnel and intellectual security, which should be ensured through the preservation and development of the intellectual potential of the enterprise and the effective work of the staff. The aim of the study is to develop theoretical and methodological foundations of the formation of personnel and intellectual component of economic security of the agricultural sector. The following methods were used in the study: dialectical method of cognition of economic phenomena, abstract and logical, analysis and synthesis, generalization. The article uses the results of expert assessment, which was conducted in accordance with the Methodology of expert assessment of the impact of individual factors on the economic security of agricultural enterprises, which has been developed by the author. The obtained results show that among the internal threats to economic security, threats related to the personnel and intellectual component (nonprofessional management of the enterprise; low level of qualification of employees; low level of employee motivation; outflow of skilled workers) occupy a prominent place. Theoretical bases of forming the mechanism of regulation of personnel and intellectual safety of the enterprise are offered. Counteraction to the threats of the personnel and intellectual component of economic security should be based on the following measures: raising the professional level of management of agricultural enterprises; provision of qualified personnel; stimulating the staff to self-development; conducting an effective youth policy with the aim of attracting young professionals in the agricultural sector; forming a sense of a unified team in employees; creation of an effective system of social support for employees; introduction of an effective and transparent system of motivation and incentives for employees, based on clear criteria for evaluating the activities of employees. Further perspectives for research in this direction should be the formation of the strategy for economic security of the agricultural sector of Ukraine, which is based on the study devoted to the management of the mechanism of regulating personnel, intellectual and other components of economic security.
Torrefied biomass in biofuel production system
Authors:   The Pennsylvania State University Department of Agricultural and Biological Engineering, State College PA, Ciolkosz D.
Published: November 2020

Ukraine produces large amounts of crop residues every year, much which could be utilized to produce biofuel. However, efficient supply chains and system configurations are needed to make such systems efficient and cost effective. One option is to integrate torrefaction, power production and biofuel production into a single, coordinated system. This approach allows for high value product (i.e. biofuel), greater utilization of the energy content of the feedstock, and supply chain efficiency. Initial analyses indicate that revenues can be enhanced through this approach, and further analyses and optimization efforts could identify a sustainable approach to renewable fuel and power production for Ukraine. The question of scale and layout remains of interest as well, and a thorough logistical study is needed to identify the most suitable configuration. Agricultural operations often benefit from smaller scales of operation, whereas fuel production processes tend to operate profitably only at very large scale. Thus, a balance must be struck between the needs of both ends of the supply chain. The processing center concept helps to balance those needs. A system such as this also has potential to synergize with other agricultural production systems, such as the production of animal feed, fertilizer, and other bio-based products. The complexities of the Ukrainian agricultural market will need to be reflected carefully in any model that seeks to assess the system's potential. Presents a concept for coupling thermal pretreatment (torrefaction with biofuel and power production for the transformation of wheat straw into a value added product for Ukraine. Torrefaction provides supply chain savings, while conversion provides added value to the product. This paradigm has potential to utilize a widely produced waste material into a valuable source of energy and possibly other products for the country.
Improving the yield and quality of winter wheat during autumn herbicide cultivation
Authors:   Polissia  National University, Moisiienko V. , Nazarchyk O. ,   Polissia  National University, Ishchenko M. ,   Polissia  National University
Published: November 2020

The main condition for growing winter wheat is the observance of proper agricultural techniques and the creation of conditions for high agricultural culture. Improving the technology in modern conditions of grain production requires knowledge of phenological and morphological features of plants, selection of adaptive varieties, means of protection of crops from harmful objects, especially weeds and avoidance of negative impact on the environment. The aim of the research was to identify the effectiveness of autumn and spring herbicide treatments on the yield and quality of winter wheat. Wheat varieties Meskal and Palyanytsia were used for these studies. We found that the term of herbicide treatment significantly affects the weediness of crops, crop formation and grain quality. Autumn herbicide treatment of winter wheat crops with Marathon, simultaneous application of 150 kg/ha of diammophos and double fertilization of plants with ammonium nitrate contributes to obtaining in the conditions of sod-podzolic sandy soils grain yields of varieties Meskal and Palyanytsia at level of 4,8–5,0 t/ha. We found that in areas not treated with herbicides, the number of weeds increased from 80 to 130 pcs/m2. The application of the herbicide Marathon (4 l/ha) in autumn ensured a reduction in the number of weeds in winter wheat crops from 86–90 pcs/m2 to 8–10 pcs /m2. Spring application of this herbicide was less effective and weed rates in these areas decreased from 100–110 pcs/m2 to 24-27 pcs/m2. Spring application of Prima herbicide (0.5 l/ha) on wheat crops showed the worst weed numbers (30–32 pcs/m2). During the autumn treatment with the herbicide Marathon, the number of productive stems was the largest: in the variety Mescal – 553 pcs/m2, and in the variety Palyanytsia – 560 pcs/m2. Reducing the weediness of winter wheat crops not only affected the number of productive stems, but also significantly improved grain quality.
Intelligent Smart Contracts for Innovative Supply Chain Management
Authors: Bottoni Paolo , Gessa Nicola , Massa Gilda , Pareschi Remo , Selim Hesham , Arcuri Enrico
Published: November 2020

We propose blockchains and smart contracts as enabling technologies for an innovative type of supply chain management, with the goal of achieving higher levels of collaboration between the companies participating in the chain, which in turn pays in the form of higher levels of profitability and economic health for the participating enterprises. Our proposal goes far beyond simply using blockchains as decentralized systems to track the origin and delivery of goods, which is what most of the current blockchain projects on supply chains are focused on. In fact, we introduce a type of smart contract aimed to solve two of the main problems that hinder the efficiency and effectiveness of supply chains, namelytrustandcoordination. Solving the problem oftrustamounts to the capability of establishing quickly and cheaply contractual relationships based on convergent business needs among parties that may not know each other, and therefore need to protect themselves from opportunistic or incorrect behavior. Solving the problem ofcoordinationconsists in creating, at convenient management costs, a control system capable of directing the objectives of the supply chain as a whole, so as to achieve a greater common good in the medium term, as an alternative to the state of affairs in which each participant pursues, on its own behalf, lower but immediate returns. Our smart contracts for innovative supply chain management replace human coordinators in tackling the problems above, thus eliminating one major obstacle to their effective solution, namely the need to trust the coordinator itself. Furthermore, in this way, by automating the process of coordination, they unburden the supply chain of a considerable management cost. Contracts of this kind not only automate contract execution as in standard smart contracts, but also adjust costs and compensations of the members of a supply chain, effectively taking up the role that was of human coordinators. Thus, we refer to them as “intelligent smart contracts.” In the course of the paper, we will illustrate an innovative supply chain architecture based on intelligent smart contracts running on blockchain, we will detail the algorithmic methodologies underlying the decision-making process of these contracts and we will outline the wider socio-economic perspectives opened by our approach.
Reversed Senescence of Retinal Pigment Epithelial Cell by Coculture With Embryonic Stem Cell via the TGFβ and PI3K Pathways
Authors: Wang Shoubi , Liu Yurun , Liu Ying , Li Chaoyang , Wan Qi , Yang Liu , Su Yaru , Cheng Yaqi , Liu Chang , Wang Xiaoran , Wang Zhichong
Published: November 2020

Retinal pigment epithelium (RPE) cellular senescence is an important etiology of age-related macular degeneration (AMD). Aging interventions based on the application of stem cells to delay cellular senescence have shown good prospects in the treatment of age-related diseases. This study aimed to investigate the potential of the embryonic stem cells (ESCs) to reverse the senescence of RPE cells and to elucidate its regulatory mechanism. The hydrogen peroxide (H2O2)-mediated premature and natural passage-mediated replicative senescent RPE cells were directly cocultured with ESCs. The results showed that the proliferative capacity of premature and replicative senescent RPE cells was increased, while the positive rate of senescence-associated galactosidase (SA-β-GAL) staining and levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were decreased. The positive regulatory factors of cellular senescence (p53, p21WAF1/CIP1, p16INK4a) were downregulated, while the negative regulatory factors of cellular senescence (Cyclin A2, Cyclin B1, Cyclin D1) were upregulated. Furthermore, replicative senescent RPE cells entered the S and G2/M phases from the G0/G1 phase. TGFβ (TGFB1, SMAD3, ID1, ID3) and PI3K (PIK3CG, PDK1, PLK1) pathway-related genes were upregulated in premature and replicative senescent RPE cells after ESCs application, respectively. We further treated ESCs-cocultured premature and replicative senescent RPE cells with SB531542 and LY294002 to inhibit the TGFβ and PI3K pathways, respectively, and found that p53, p21WAF1/CIP1 and p16INK4a were upregulated, while Cyclin A2, Cyclin B1, Cyclin D1, TGFβ, and PI3K pathway-related genes were downregulated, accompanied by decreased proliferation and cell cycle transition and increased positive rates of SA-β-GAL staining and levels of ROS and MMP. In conclusion, we demonstrated that ESCs can effectively reverse the senescence of premature and replicative senescent RPE cells by a direct coculture way, which may be achieved by upregulating the TGFβ and PI3K pathways, respectively, providing a basis for establishing a new therapeutic option for AMD.
Direct Visualization of Actin Filaments and Actin-Binding Proteins in Neuronal Cells
Authors: Jung Minkyo , Kim Doory , Mun Ji Young
Published: November 2020

Actin networks and actin-binding proteins (ABPs) are most abundant in the cytoskeleton of neurons. The function of ABPs in neurons is nucleation of actin polymerization, polymerization or depolymerization regulation, bundling of actin through crosslinking or stabilization, cargo movement along actin filaments, and anchoring of actin to other cellular components. In axons, ABP–actin interaction forms a dynamic, deep actin network, which regulates axon extension, guidance, axon branches, and synaptic structures. In dendrites, actin and ABPs are related to filopodia attenuation, spine formation, and synapse plasticity. ABP phosphorylation or mutation changes ABP–actin binding, which regulates axon or dendritic plasticity. In addition, hyperactive ABPs might also be expressed as aggregates of abnormal proteins in neurodegeneration. Those changes cause many neurological disorders. Here, we will review direct visualization of ABP and actin using various electron microscopy (EM) techniques, super resolution microscopy (SRM), and correlative light and electron microscopy (CLEM) with discussion of important ABPs in neuron.
TMEM132A, a Novel Wnt Signaling Pathway Regulator Through Wntless (WLS) Interaction
Authors: Li Binbin , Niswander Lee A.
Published: November 2020

Wnt signaling pathway plays indispensable roles in embryonic development and adult tissue homeostasis. However, the regulatory mechanisms involved in Wnt ligand trafficking within and secretion from the signal sending cells is still relatively uncharacterized. Here, we discover a novel regulator of Wnt signaling pathway called transmembrane protein 132A (TMEM132A). Our evidence shows a physical and functional interaction of TMEM132A with the Wnt ligand transporting protein Wntless (WLS). We show that TMEM132A stabilizes Wnt ligand, enhances WLS–Wnt ligand interaction, and activates the Wnt signaling pathway. Our results shed new light on the cellular mechanism underlying the fundamental aspect of WNT secretion from Wnt signal sending cells.
Particulate Matter Exposure During Oocyte Maturation: Cell Cycle Arrest, ROS Generation, and Early Apoptosis in Mice
Authors: Jo Yu-Jin , Yoon Seung-Bin , Park Byoung-Jin , Lee Sang Il , Kim Ki Jin , Kim Se-Yong , Kim Minseong , Lee Jun-Ki , Lee Sang-Yong , Lee Dong-Ho , Kwon Taeho , Son Yeonghoon , Lee Ja-Rang , Kwon Jeongwoo , Kim Ji-Su
Published: November 2020

Particulate matter (PM) is a general atmospheric pollutant released into the air by an anthropogenic and naturally derived mixture of substances. Current studies indicate that fine dust can result in different health defects, including endothelial dysfunction, asthma, lung cancer, cardiovascular diseases, uterine leiomyoma, deterioration in sperm quality, and overall birth impairment. However, the most prominent effects of PM10(diameter < 10 μM) exposure on the female reproductive system, especially with respect to oocyte maturation, remain unclear. In the present study, maturing mouse oocytes were treated with PM10and the phenotypes of the resulting toxic effects were investigated. Exposure to PM10led to impairment of maturation capacity by inducing cell cycle arrest and blocking normal polar body extrusion duringin vitromaturation and activation of fertilization of mouse oocytes. Additionally, defects in tubulin formation and DNA alignment were observed in PM10-treated oocytes during metaphase I to anaphase/telophase I transition. Moreover, PM10induced reactive oxygen species generation, mitochondrial dysfunction, DNA damage, and early apoptosis. Taken together, these results indicate that PM10exposure leads to a decline in oocyte quality and affects the subsequent embryonic development potential of mammalian oocytes.
Treating Hyperglycemia From Eryngium caeruleum M. Bieb: In-vitro α-Glucosidase, Antioxidant, in-vivo Antidiabetic and Molecular Docking-Based Approaches
Authors: Sadiq Abdul , Rashid Umer , Ahmad Sadiq , Zahoor Mohammad , AlAjmi Mohamed F. , Ullah Riaz , Noman Omar M. , Ullah Farhat , Ayaz Muhammad , Khan Iftikhar , Islam Zia-Ul , Ali Waqar
Published: November 2020

Natural-based drugs are believed to be safe, effective and economical. Based on the medicinal importance of the genus Eryngium and unexplored nature ofEryngium caeruleum, we have evaluated its antidiabetic and antioxidant potentials. Bothin-vitroandin-vivoassays have been carried out for antidiabetic assays. The antioxidant activity was determined by using different free radicals [i.e., 1,1-diphenyl,2-picrylhydrazyl (DPPH), 2,2-azinobis[3-ethylbenzthiazoline]-6-sulfonic acid (ABTS), and hydrogen peroxide (H2O2)]. Moreover, different phytoconstituents were identified in the most active solvent fraction by GC-MS analysis. Furthermore, comparative fingerprints of methanolic extract and chloroform fraction were also analyzed via High Performance Liquid Chromatography coupled with Diode Array Detector (HPLC-DAD). The crude methanolic extract ofE. caeruleum(Ec.Cr) and its sub-fractions [i.e.,n-hexane (Ec.Hex), chloroform (Ec.Chf), ethyl acetate (Ec.EtAc), and aqueous (Ec.Aq) were employed in this study]. In the α-glucosidase inhibition assay, a concentration-dependent inhibitory response was observed against the enzyme. The most active sample was Ec.Chf which revealed an IC50of 437 μg/ml in comparison to the standard acarbose (IC5025 μg/ml). The rest of the samples showed moderate inhibition of α-glucosidase. In antioxidant assays, Ec.Chf and Ec.Cr exhibited a considerable scavenging effect against all the free radicals. The IC50values recorded for Ec.Chf were 112, 109, and 150 μg/ml against DPPH, ABTS, and H2O2respectively. Based on thein-vitropotential of Ec.Chf, this was subjected to thein-vivomodel experiment. The Ec.Chf lowered the blood glucose level up to 10.3 mmol/L at 500 μg/Kg. The Ec.Chf was also subjected to GC-MS analysis. The GC-MS analysis confirmed the presence of 60 compounds. The identified phytoconstituents consist of some essential compounds previously reported with antidiabetic and antioxidant studies, which include thymol, tocopherol, phytol, nerolidol, (I)-neophytadiene, linolenic acid, and falcarinol. Similarly, the HPLC-DAD chromatograms of Ec.Cr and Ec.Chf exhibited a variety of peaks, which further demonstrates the possibility of important phytochemicals. In a nutshell, we can conclude thatEryngium caeruleumis a potential source of bioactive compounds which may be beneficial for the management of ailments like diabetes and free radicals mediated disorders. Molecular docking was performed to explore the possible role of all the identified bioactive compounds in the chloroform fraction ofEryngium caeruleuminto active sites of the homology model of α-glucosidase.
Electrochemical Sensors Based on Covalent Organic Frameworks: A Critical Review
Authors: Chen Sidi , Yuan Baiqing , Liu Gang , Zhang Daojun
Published: November 2020

The metal-free cousins of metal-organic frameworks, covalent organic frameworks (COFs), are a class of pre-designable crystalline polymers composed of light elements and connected by strong covalent bonds. COFs are being given more and more attention in the electrochemical sensor field due to their fascinating properties, such as highly tunable porosity, intrinsic chemical and thermal stability, structural diversity, large specific surface area, and unique adsorption characteristics. However, there are still some key issues regarding COFs that need to be urgently resolved before they can be effectively applied in electrochemical sensing. In this review, we summarized recent achievements in developing novel electrochemical sensors based on COFs, and discussed the key fundamental and challenging issues that need to be addressed, including the mechanisms underlying charge transport, methods to improve electrical conductivity, immobilization methods on different substrates, synthesis strategies for nanoscale COFs, and the application of COFs in different fields. Finally, the challenges and outlooks in this promising field are tentatively proposed.
Serum Uric Acid and Left Ventricular Mass in Essential Hypertension
Authors: Visco Valeria , Pascale Antonietta Valeria , Virtuoso Nicola , Mongiello Felice , Cinque Federico , Gioia Renato , Finelli Rosa , Mazzeo Pietro , Manzi Maria Virginia , Morisco Carmine , Rozza Francesco , Izzo Raffaele , Cerasuolo Federica , Ciccarelli Michele , Iaccarino Guido
Published: November 2020

Serum uric acid (sUA) has been associated with cardiovascular risk. Although the recent mechanistic hypothesis poses the basis for the association between sUA and left ventricular mass index (LVMi), the issue remains poorly investigated in a clinical setup. Through a retrospective analysis of the database of the departmental Hypertension Clinic of University Hospital of Salerno Medical School, we identified 177 essential hypertensives (age 60.3 ± 13.3 years; 85 men), free from uric acid-modulating medications and severe chronic kidney disease, and whose sUA values, anthropometric, clinical, and echocardiographic data were available. In the studied cohort, the average duration of hypertension was 8.4 ± 7.1 years. LVMi associated with classical determinants, such as age, blood pressure, and kidney function, although after multivariate correction, only age remained significant. Also, sUA correlated positively with LVMi, as well as body size, metabolism, and kidney function. In a multivariate analysis, sUA confirmed the independent association with LVMi. Also, levels of sUA >5.6 mg/dl are associated with larger cardiac size. We confirmed our data in a replicate analysis performed in a larger population (1,379 hypertensives) from an independent clinic. Our results demonstrate that sUA increases with LVMi, and a cutoff of 5.6 mg/dl predict larger LV sizes. Our data suggest that hyperuricemia might help to stratify the risk of larger cardiac size in hypertensives.
Repression of MicroRNA-124-3p Alleviates High-Fat Diet–Induced Hepatosteatosis by Targeting Pref-1
Authors: Wang Guan , Zou Haibo , Lai Chunyou , Huang Xiaolun , Yao Yutong , Xiang Guangming
Published: November 2020

Nonalcoholic fatty liver disease (NAFLD) is the common disease in the liver, which is associated with metabolic syndrome and hepatocellular carcinoma. Accumulated evidence establishes that small non-coding microRNAs (miRNAs) contribute to the initiation and progression of NAFLD. However, the molecular repertoire of miRNA in NAFLD is still largely unknown. Here, using an integrative approach spanning bioinformatic analysis and functional approaches, we demonstrate that miR-124-3p participates in the development of NAFLD by directly targeting preadipocyte factor-1 (Pref-1). In response to high-fat diet (HFD), expression of miR-124-3p was increased in the liver. Inhibition of miR-124-3p expression led to a dramatic reduction of triglyceride contents in hepatocytes, in parallel with decreased inflammatory factors. Mechanistically, miR-124-3p directly controls the transcription of Pref-1, a secretory factor that has been proved to resist metabolic syndrome. Our work identifies a novel molecular axis in hepatosteatosis, and highlights miR-124-3p/Pref-1 as potential targets for clinical interventions of NAFLD.
Behavioral Feeding Circuit: Dietary Fat-Induced Effects of Inflammatory Mediators in the Hypothalamus
Authors: Poon Kinning
Published: November 2020

Excessive dietary fat intake has extensive impacts on several physiological systems and can lead to metabolic and nonmetabolic disease. In animal models of ingestion, exposure to a high fat diet during pregnancy predisposes offspring to increase intake of dietary fat and causes increase in weight gain that can lead to obesity, and without intervention, these physiological and behavioral consequences can persist for several generations. The hypothalamus is a region of the brain that responds to physiological hunger and fullness and contains orexigenic neuropeptide systems that have long been associated with dietary fat intake. The past fifteen years of research show that prenatal exposure to a high fat diet increases neurogenesis of these neuropeptide systems in offspring brain and are correlated to behavioral changes that induce a pro-consummatory and obesogenic phenotype. Current research has uncovered several potential molecular mechanisms by which excessive dietary fat alters the hypothalamus and involve dietary fatty acids, the immune system, gut microbiota, and transcriptional and epigenetic changes. This review will examine the current knowledge of dietary fat-associated changes in the hypothalamus and the potential pathways involved in modifying the development of orexigenic peptide neurons that lead to changes in ingestive behavior, with a special emphasis on inflammation by chemokines.
Pathophysiology of NAFLD and NASH in Experimental Models: The Role of Food Intake Regulating Peptides
Authors: Kořínková L. , Pražienková V. , Černá L. , Karnošová A. , Železná B. , Kuneš J. , Maletínská Lenka
Published: November 2020

Obesity, diabetes, insulin resistance, sedentary lifestyle, and Western diet are the key factors underlying non-alcoholic fatty liver disease (NAFLD), one of the most common liver diseases in developed countries. In many cases, NAFLD further progresses to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and to hepatocellular carcinoma. The hepatic lipotoxicity and non-liver factors, such as adipose tissue inflammation and gastrointestinal imbalances were linked to evolution of NAFLD. Nowadays, the degree of adipose tissue inflammation was shown to directly correlate with the severity of NAFLD. Consumption of higher caloric intake is increasingly emerging as a fuel of metabolic inflammation not only in obesity-related disorders but also NAFLD. However, multiple causes of NAFLD are the reason why the mechanisms of NAFLD progression to NASH are still not well understood. In this review, we explore the role of food intake regulating peptides in NAFLD and NASH mouse models. Leptin, an anorexigenic peptide, is involved in hepatic metabolism, and has an effect on NAFLD experimental models. Glucagon-like peptide-1 (GLP-1), another anorexigenic peptide, and GLP-1 receptor agonists (GLP-1R), represent potential therapeutic agents to prevent NAFLD progression to NASH. On the other hand, the deletion of ghrelin, an orexigenic peptide, prevents age-associated hepatic steatosis in mice. Because of the increasing incidence of NAFLD and NASH worldwide, the selection of appropriate animal models is important to clarify aspects of pathogenesis and progression in this field.
ARHGAP21 Acts as an Inhibitor of the Glucose-Stimulated Insulin Secretion Process
Authors: Ferreira Sandra M. , Costa-Júnior José M. , Kurauti Mirian A. , Leite Nayara C. , Ortis Fernanda , Rezende Luiz F. , Barbosa Helena C. , Boschero Antonio C. , Santos Gustavo J.
Published: November 2020

ARHGAP21 is a RhoGAP protein implicated in the modulation of insulin secretion and energy metabolism. ARHGAP21 transient-inhibition increase glucose-stimulated insulin secretion (GSIS) in neonatal islets; however, ARHGAP21 heterozygote mice have a reduced insulin secretion. These discrepancies are not totally understood, and it might be related to functional maturation of beta cells and peripheral sensitivity. Here, we investigated the real ARHGAP21 role in the insulin secretion process using an adult mouse model of acute ARHGAP21 inhibition, induced by antisense. After ARHGAP21 knockdown induction by antisense injection in 60-day old male mice, we investigated glucose and insulin tolerance test, glucose-induced insulin secretion, glucose-induced intracellular calcium dynamics, and gene expression. Our results showed that ARHGAP21 acts negatively in the GSIS of adult islet. This effect seems to be due to the modulation of important points of insulin secretion process, such as the energy metabolism (PGC1α), Ca2+signalization (SYTVII), granule-extrusion (SNAP25), and cell-cell interaction (CX36). Therefore, based on these finds, ARHGAP21 may be an important target in Diabetes Mellitus (DM) treatment.
Integrated Multichip Analysis Identifies Potential Key Genes in the Pathogenesis of Nonalcoholic Steatohepatitis
Authors: Ye Jianzhong , Lin Yishuai , Wang Qing , Li Yating , Zhao Yajie , Chen Lijiang , Wu Qing , Xu Chunquan , Zhou Cui , Sun Yao , Ye Wanchun , Bai Fumao , Zhou Tieli
Published: November 2020

Background

Nonalcoholic steatohepatitis (NASH) is rapidly becoming a major chronic liver disease worldwide. However, little is known concerning the pathogenesis and progression mechanism of NASH. Our aim here is to identify key genes and elucidate their biological function in the progression from hepatic steatosis to NASH.

Methods

Gene expression datasets containing NASH patients, hepatic steatosis patients, and healthy subjects were downloaded from the Gene Expression Omnibus database, using the R packages biobase and GEOquery. Differentially expressed genes (DEGs) were identified using the R limma package. Functional annotation and enrichment analysis of DEGs were undertaken using the R package ClusterProfile. Protein-protein interaction (PPI) networks were constructed using the STRING database.

Results

Three microarray datasets GSE48452, GSE63067 and GSE89632 were selected. They included 45 NASH patients, 31 hepatic steatosis patients, and 43 healthy subjects. Two up-regulated and 24 down-regulated DEGs were found in both NASH patients vs. healthy controls and in steatosis subjects vs. healthy controls. The most significantly differentially expressed genes were FOSB (P = 3.43×10-15), followed by CYP7A1 (P = 2.87×10-11), and FOS (P = 6.26×10-11). Proximal promoter DNA-binding transcription activator activity, RNA polymerase II-specific (P = 1.30×10-5) was the most significantly enriched functional term in the gene ontology analysis. KEGG pathway enrichment analysis indicated that the MAPK signaling pathway (P = 3.11×10-4) was significantly enriched.

Conclusion

This study characterized hub genes of the liver transcriptome, which may contribute functionally to NASH progression from hepatic steatosis.
Post-Fire Vegetation Response in a Repeatedly Burned Low-Elevation Sagebrush Steppe Protected Area Provides Insights About Resilience and Invasion Resistance
Authors: Rodhouse Thomas J. , Irvine Kathryn M. , Bowersock Lisa
Published: November 2020

Sagebrush steppe ecosystems are threatened by human land-use legacies, biological invasions, and altered fire and climate dynamics. Steppe protected areas are therefore of heightened conservation importance but are few and vulnerable to the same impacts broadly affecting sagebrush steppe. To address this problem, sagebrush steppe conservation science is increasingly emphasizing a focus on resilience to fire and resistance to non-native annual grass invasion as a decision framework. It is well-established that the positive feedback loop between fire and annual grass invasion is the driving process of most contemporary steppe degradation. We use a newly developed ordinal zero-augmented beta regression model fit to large-sample vegetation monitoring data from John Day Fossil Beds National Monument, USA, spanning 7 years to evaluate fire responses of two native perennial foundation bunchgrasses and two non-native invasive annual grasses in a repeatedly burned, historically grazed, and inherently low-resilient protected area. We structured our model hierarchically to support inferences about variation among ecological site types and over time after also accounting for growing-season water deficit, fine-scale topographic variation, and burn severity. We use a state-and-transition conceptual diagram and abundances of plants listed in ecological site reference conditions to formalize our hypothesis of fire-accelerated transition to ecologically novel annual grassland. Notably, big sagebrush (Artemisia tridentata) and other woody species were entirely removed by fire. The two perennial grasses, bluebunch wheatgrass (Pseudoroegneria spicata) and Thurber's needlegrass (Achnatherum thurberianum) exhibited fire resiliency, with no apparent trend after fire. The two annual grasses, cheatgrass (Bromus tectorum) and medusahead (Taeniatherum caput-medusae), increased in response to burn severity, most notably medusahead. Surprisingly, we found no variation in grass cover among ecological sites, suggesting fire-driven homogenization as shrubs were removed and annual grasses became dominant. We found contrasting responses among all four grass species along gradients of topography and water deficit, informative to protected-area conservation strategies. The fine-grained influence of topography was particularly important to variation in cover among species and provides a foothold for conservation in low-resilient, aridic steppe. Broadly, our study demonstrates how to operationalize resilience and resistance concepts for protected areas by integrating empirical data with conceptual and statistical models.
Haplotype Analysis of Genomic Prediction Using Structural and Functional Genomic Information for Seven Human Phenotypes
Authors: Liang Zuoxiang , Tan Cheng , Prakapenka Dzianis , Ma Li , Da Yang
Published: November 2020

Genomic prediction using multi-allelic haplotype models improved the prediction accuracy for all seven human phenotypes, the normality transformed high density lipoproteins, low density lipoproteins, total cholesterol, triglycerides, weight, and the original height and body mass index without normality transformation. Eight SNP sets with 40,941-380,705 SNPs were evaluated. The increase in prediction accuracy due to haplotypes was 1.86-8.12%. Haplotypes using fixed chromosome distances had the best prediction accuracy for four phenotypes, fixed number of SNPs for two phenotypes, and gene-based haplotypes for high density lipoproteins and height (tied for best). Haplotypes of coding genes were more accurate than haplotypes of all autosome genes that included both coding and noncoding genes for triglycerides and weight, and nearly the same as haplotypes of all autosome genes for the other phenotypes. Haplotypes of noncoding genes (mostly lncRNAs) only improved the prediction accuracy over the SNP models for high density lipoproteins, total cholesterol, and height. ChIP-seq haplotypes had better prediction accuracy than gene-based haplotypes for total cholesterol, body mass index and low density lipoproteins. The accuracy of ChIP-seq haplotypes was most striking for low density lipoproteins, where all four haplotype models with ChIP-seq haplotypes had similarly high prediction accuracy over the best prediction model with gene-based haplotypes. Haplotype epistasis was shown to be the reason for the increased accuracy due to haplotypes. Low density lipoproteins had the largest haplotype epistasis heritability that explained 14.70% of the phenotypic variance and was 31.27% of the SNP additive heritability, and the largest increase in prediction accuracy relative to the best SNP model (8.12%). Relative to the SNP additive heritability of the same regions, noncoding genes had the highest haplotype epistasis heritability, followed by coding genes and ChIP-seq for the seven phenotypes. SNP and haplotype heritability profiles showed that the integration of SNP and haplotype additive values compensated the weakness of haplotypes in estimating SNP heritabilities for four phenotypes, whereas models with haplotype additive values fully accounted for SNP additive values for three phenotypes. These results showed that haplotype analysis can be a method to utilize functional and structural genomic information to improve the accuracy of genomic prediction.
COVID-19 Effect on Access to Maternal Health Services in Kenya
Authors: Oluoch-Aridi Jackline , Chelagat Tecla , Nyikuri Mary M. , Onyango Joseph , Guzman Danice , Makanga Cindy , Miller-Graff Laura , Dowd Robert
Published: November 2020

Introduction: Maternal mortality continues to be one of the biggest challenges of the health system in Kenya. Informal settlements in Kenya have been known to have higher rates of maternal mortality and also receive maternity services of varied quality. Data assessing progress on key maternal health indicators within informal settlements are also often scarce. The COVID-19 pandemic hit Kenya in March this year and so far, the impact of the pandemic on access to maternal health has not been established. This study aims to add to the body of knowledge by investigating the effects of the COVID-19 pandemic and mitigation strategies on access to health care services in informal settlements.

Methods: Qualitative methods using in-depth interviews were used to assess women's experiences of maternity care during the COVID-19 era and the impact of proposed mitigation strategies such as the lockdown and the curfew. Other aspects of the maternity experience such as women's knowledge of COVID-19, their perceived risk of infection, access to health facilities, perceived quality of care were assessed. Challenges that women facing as a result of the lockdown and curfew with respect to maternal health access and quality were also assessed.

Results: Our findings illustrate that there was a high awareness of the symptoms and preventative measures for COVID-19 amongst women in informal settlements. Our findings also show that women's perception of risk to themselves was high, whereas risk to family and friends, and in their neighborhood was perceived as low. Less than half of women reported reduced access due to fear of contracting Coronavirus, Deprioritization of health services, economic constraints, and psychosocial effects were reported due to the imposed lockdown and curfew. Most respondents perceived improvements in quality of care due to short-waiting times, hygiene measures, and responsive health personnel. However, this was only reported for the outpatient services and not in-patient services.

Conclusion: The most important recommendation was for the Government to provide food followed by financial support and other basic amenities. This has implications for the Government's mitigation measures that are focused on public health measures and lack social safety-net approaches for the most vulnerable communities.
Specific Targeting of Lymphoma Cells Using Semisynthetic Anti-Idiotype Shark Antibodies
Authors: Macarrón Palacios Arturo , Grzeschik Julius , Deweid Lukas , Krah Simon , Zielonka Stefan , Rösner Thies , Peipp Matthias , Valerius Thomas , Kolmar Harald
Published: November 2020

The B-cell receptor (BCR) is a key player of the adaptive immune system. It is a unique part of immunoglobulin (Ig) molecules expressed on the surface of B cells. In case of many B-cell lymphomas, the tumor cells express a tumor-specific and functionally active BCR, also known as idiotype. Utilizing the idiotype as target for lymphoma therapy has emerged to be demanding since the idiotype differs from patient to patient. Previous studies have shown that shark-derived antibody domains (vNARs) isolated from a semi-synthetic CDR3-randomized library allow for the rapid generation of anti-idiotype binders. In this study, we evaluated the potential of generating patient-specific binders against the idiotype of lymphomas. To this end, the BCRs of three different lymphoma cell lines SUP-B8, Daudi, and IM-9 were identified, the variable domains were reformatted and the resulting monoclonal antibodies produced. The SUP-B8 BCR served as antigen in fluorescence-activated cell sorting (FACS)-based screening of the yeast-displayed vNAR libraries which resulted after three rounds of screening in the enrichment of antigen-binding vNARs. Five vNARs were expressed as Fc fusion proteins and consequently analyzed for their binding to soluble antigen using biolayer interferometry (BLI) revealing binding constants in the lower single-digit nanomolar range. These variants showed specific binding to the parental SUP-B8 cell line confirming a similar folding of the recombinantly expressed proteins compared with the native cell surface-presented BCR. First initial experiments to utilize the generated vNAR-Fc variants for BCR-clustering to induce apoptosis or ADCC/ADCP did not result in a significant decrease of cell viability. Here, we report an alternative approach for a personalized B-cell lymphoma therapy based on the construction of vNAR-Fc antibody-drug conjugates to enable specific killing of malignant B cells, which may widen the therapeutic window for B-cell lymphoma therapy.
BAFF Blockade Attenuates Inflammatory Responses and Intestinal Barrier Dysfunction in a Murine Endotoxemia Model
Authors: Quan Runze , Chen Chaoyue , Yan Wei , Zhang Ying , Zhao Xi , Fu Yu
Published: November 2020

B cell-activating factor (BAFF) production is increased in septic patients. However, the specific role of BAFF in sepsis remains unknown. This study was designed to investigate the expression and function of BAFF in an experimental endotoxemia model and to identify the potential mechanisms. We established an endotoxemia mouse (6–8 weeks, 20–22 g) model by administering 30 mg/kg lipopolysaccharide (LPS). BAFF levels in the circulating system and organ tissues were measured 4 and 8 h after LPS injection. Survival rates in the endotoxemia mice were monitored for 72 h after BAFF blockade. The effects of BAFF blockade on systemic and local inflammation, organ injuries, and intestinal barrier function were also evaluated 4 h after LPS treatment. BAFF production was systemically and locally elevated after LPS challenge. BAFF blockade improved the survival rate, systemic inflammation, and multi-organ injuries. Moreover, BAFF blockade attenuated both intestinal inflammation and impaired intestinal permeability. BAFF blockade upregulated ZO-1 and occludin protein levels via the NF-κB/MLCK/MLC signaling pathway. These results suggested that BAFF blockade protects against lethal endotoxemia at least partially by alleviating inflammation, multi-organ injuries, and improving intestinal barrier function and provides a novel focus for further research on sepsis and experimental evidence for clinical therapy.
Targeting Interleukin-2-Inducible T-Cell Kinase (ITK) Differentiates GVL and GVHD in Allo-HSCT
Authors: Mammadli Mahinbanu , Huang Weishan , Harris Rebecca , Sultana Aisha , Cheng Ying , Tong Wei , Pu Jeffery , Gentile Teresa , Dsouza Shanti , Yang Qi , Bah Alaji , August Avery , Karimi Mobin
Published: November 2020

Allogeneic hematopoietic stem cell transplantation is a potentially curative procedure for many malignant diseases. Donor T cells prevent disease recurrence via graft-versus-leukemia (GVL) effect. Donor T cells also contribute to graft-versus-host disease (GVHD), a debilitating and potentially fatal complication. Novel treatment strategies are needed which allow preservation of GVL effects without causing GVHD. Using murine models, we show that targeting IL-2-inducible T cell kinase (ITK) in donor T cells reduces GVHD while preserving GVL effects. Both CD8+ and CD4+ donor T cells from Itk-/- mice produce less inflammatory cytokines and show decrease migration to GVHD target organs such as the liver and small intestine, while maintaining GVL efficacy against primary B-cell acute lymphoblastic leukemia (B-ALL). Itk-/- T cells exhibit reduced expression of IRF4 and decreased JAK/STAT signaling activity but upregulating expression of Eomesodermin (Eomes) and preserve cytotoxicity, necessary for GVL effect. Transcriptome analysis indicates that ITK signaling controls chemokine receptor expression during alloactivation, which in turn affects the ability of donor T cells to migrate to GVHD target organs. Our data suggest that inhibiting ITK could be a therapeutic strategy to reduce GVHD while preserving the beneficial GVL effects following allo-HSCT treatment.