bluuebunny/crossref_metadata_2025 huggingface dataset:
Benthic community composition of temperate mesophotic ecosystems (TMEs) in New Zealand: sponge domination and contribution to habitat complexity
Authors: Harris B , Davy SK , Bell JJ
Published: May 2021

Temperate mesophotic ecosystems (TMEs) typically occur between 30 and 150 m depth and support rich benthic communities. However, despite their widespread distribution and ecological importance, TMEs are one of the most poorly studied marine ecosystems globally. We measured changes in the benthic community composition of rocky reefs through the infralittoral and mesophotic zone from 5 to 120 m at 6 locations across New Zealand (the Poor Knights Islands, the inner, mid-, and outer regions of the Fiordland Marine Area [FMA], and the North and South Taranaki Bights) which we considered as potential shallow-water TME surrogates due to these sites having environmental conditions and biological communities similar to deeper-water communities. Benthic community data were analysed from videos and photographs collected using SCUBA (<30 m) and a remotely operated vehicle (ROV) (>30 m). We found significant changes in community composition with depth at all locations, suggesting that TMEs provide habitats different from those in shallower water. We consistently found that TME benthic communities were dominated by sponges, but their abundance varied significantly with depth at 3 out of 4 locations, while the morphological composition of these assemblages changed with depth at all locations. Given their particularly high abundance and morphological complexity, we suggest that sponge assemblages make an important contribution to habitat complexity in benthic TME communities.
Сlinical and neurological characteristics of patients with initial manifestations of chronic cerebro-vascular insufficiency of different
Authors:   Lviv National Medical University. Danylo Halytsky, Andriiuk L. V. , Yermolayeva A.V. ,   Lviv National Medical University. Danylo Halytsky
Published: May 2021

Keywords: cerebrovascular disease, clinico-neurological characteristics, quality of life. The results of examination of 100 patients with cerebrovascular disease are represented. Analysis of objective data indicating, thatcognitive, coordinative, and thinking impairments are leading in the compensated and subcompensated stages of cerebrovascular disease. These indicators make possible to take into consideration the individual characteristics of each patient for developing a comprehensive program of physical and medical rehabilitation.
Methods of qualitative and quantitative risk analysis
Authors: Shurda K.
Published: May 2021

The article clarifies the current issues of the existing methodology for assessing the risks that arise in the management process. This is dictated by the need to analyze and assess the risk for further optimal management of economic activity, given that risk is an integral part of any process. It is emphasized that the risk assessment is to compare the level of risk with the level of acceptability, and the basis for the assignment to the group of acceptable risks is a system of parameters, different for each specific risk. Riskassessment is performed to determine the probability and size of losses that characterize the magnitude (or degree) of risk, and is carried out by various methods, which can be combined into two groups: qualitative methods of risk analysis and quantitative methods. Risk assessment is an assessment of probability, point or integral, statistical or expert. In this case, risk management is limited by the probability of adverse events. It is established that the main task of qualitative analysis is to identify possible types of risk, potential risk areas and factors influencing the level of risk. In market conditions, the problem of risk analysis and assessment is becoming increasingly important as an important component of management theory and practice. Thus, the need for research on this issue is not only relevant, but also significantly increases during the period of dynamic changes in the economic and social development of Ukraine. In this regard, the study and analysis of risks occupies an important place in the economy, as well as in ecology and other areas of human activity.
Economic efficiency of seedling method of growing Melissa officinalis L. under drip irrigation
Authors: Pryvedeniuk N.
Published: May 2021

An economic evaluation of seedling cultivation of lemon balm under drip irrigation was carried out. The profitability of growing the crop with different number of planted plants per unit area is calculated. It was found that the costs in the first year of growing lemon balm can range from 165.5 to 209.4 thousand UAH/ha, for the second year of cultivation from 154.8 to 171.3 thousand UAH/ha. The highest economic indicators were obtained in the variant with a planting density of 55.6 thousand plants/ha, where the level of profitability was 24% in the first year and 118% in the second year of cultivation. The cost structure is analyzed and the factors that most significantly affect the cost of raw materials are identified. The high efficiency of the seedling method of growing lemon balm in the conditions of drip irrigation as a means of intensification of growing technology is proved.
Ecological consequences of intensification of agricultural production.
Authors: Chumachenko O. , Kryvoviaz Y. , Hrehul V.
Published: May 2021

The problem of intensification of agricultural production in the conditions of rapidly growing population is highlighted. In agriculture, their severity is even more pronounced, because this sector of the economy has always been characterized by its problems and actively attracted public attention. Among these problems and unsolved problems, recently, issues related to the intensification of agricultural production, which has significant features, have become especially relevant. Its consistent implementation affects important aspects of agricultural theory, primarily related to the law of declining soil fertility, the theory and conditions of formation of differential land rent. From a practical point of view, the intensification of agricultural production, the driving force of which is scientific and technological progress and systemic technical and technological transformations, provides a set of measures to ensure environmental sustainability, rationalization of nature. Their scientific and theoretical development becomes an objective necessity in the formation of a market economy and market relations. The management practice of agricultural enterprises requires a deeper justification of measures to intensify agricultural production. Thus, the intensification of agriculture is not only a vital economic strategy, but also largely social. After all, the formation and development of agricultural production on the basis of intensification provides income to enterprises in the agricultural sector, which will improve the living conditions of the rural population.
Antioxidant enzymes activity in grain sorghum plants under the action of herbicide, a plant growth regulator and a biopreparation
Authors: Karpenko V. , Krasnoshtan V. , Prytuliak R. , Mostoviak I. , Hnatiuk M.
Published: May 2021

Herbicides, being substances with a high physiological activity, can affect not only weeds but also cultural plants. At the same time, there are many evidences that usage of plant growth regulators and pre-sowing seeds treatment by biological preparations can reduce the potential harmful impact of herbicides. Antioxidant systems are one of the first plant systems which react to the permeation of exogenous physiologically active substances. Therefore, one of the effective ways to estimate the influence of different preparations on plants condition is estimation of the antioxidant enzymes activity, particularly — catalase, peroxidase and polyphenoloxidase. To estimate enzymes activity in leaves of grain sorghum, a field experiment has been laid. It was conducted in crop rotation of the biology department of Uman national university of horticulture during 2019–2020. In the experiments were used: grain sorghum (Sorghum bicolor (L.) Moench) of the Milo W hybrid, herbicide Cytadel 25 OD in rates of 0,6; 0,8 and 1,0 l/ha, plant growth regulator Endofit L1 (30 ml/ha) and biopreparation Bioarsenal (800 g/100 kg). Enzymes activity was estimated in phases of tillering and throwing panicles. It was established that the enzymes activity of grain sorghum depended on the herbicide rate and raised simultaneously with its increasement. However, application of the herbicide in conjunction with the plant growth regulator Endofit L1 caused more significant increasement of the investigated enzymes compared to the variants where only herbicide was applied. The similar effect established in variants where the herbicide was applied on the background of pre-sowing seeds treatment by the biopreparation Bioarsenal. The highest activity of the antioxidant enzymes established in the variants where the herbicide Citadel 25 OD in rates of 0,6; 0,8 and 1,0 l/ha was applied in conjunction with the plant growth regulator Endofit L1 on the background of pre-sowing seeds treatment by the biopreparation Bioarsenal. It indicates increasement of the plant’s antioxidant status in case of using this combination of preparates.
Ways of attracting investment in the territory and objects of the nature reserve fund of Ukraine
Authors: Makhinko R.
Published: May 2021

The article, based on the analysis of scientific literature and the current legal framework, reveals the main ways and directions of attracting investment in the territory and objects of nature reserves of Ukraine in today’s conditions, a detailed description of the main investment entities in this area. The only acceptable tools for investing in nature reserves are public-private partnership mechanisms. The use of tools of private-public partnership and involvement of business in the management of nature reserves can increase the level of integration of natural resources into economic circulation through the construction of chains, schemes, value added production networks on the basis of both individual and especially — corporate governance within the business ecosystem of the territorial entity to which these resources and assets should be involved. It should be noted that at different stages of the implementation of the European integration algorithm for the development of public-private partnership will prevail different tools of this mechanism. Thus, in the first, deconcentration stage — budget decentralization, unification of communities and delegation of powers in the management of natural resources, including nature reserve facilities, united territorial communities from state to local authorities, deconcentration of resources will prevail. In the second stage, devolution with the end of delimitation and delegation of extended powers to the territories with the simultaneous introduction of a project approach to the management of natural assets and the beginning of the creation of territorial corporations for the management of nature reserves. At the third, divestiture stage, the formation of profitable territorial corporate entities of the cluster type, operating in the use of natural assets, ie individual territorial corporations of sustainable development with a diversified financial and investment component. The article also reveals in detail the role of institutional support for the process of investing in domestic nature reserves, and on this basis identifies a key range of existing issues.
Ecological and economic problems of forest use on radioactively contaminated land in Kyiv region
Authors: Zamula H.
Published: May 2021

The article identifies and analyzes the main environmental and economic problems of forestry in Kyiv region, which were exposed to radiation pollution as a result of the Chernobyl disaster. The data of liquid wood harvesting in the region are analyzed taking into account the contaminated territories and the positive dynamics of forest reproduction for the last years is presented. The main economic gaps in the loss of forestry of the region have been identified. The current indicators of radiation pollution of the territories are given, which allows to use them in further forecasts and researches. Emphasis is placed on the insufficient competitiveness of forest enterprises of Kyiv OULMG.
Healthcare startups and ecosystems: Insights from an emerging market economy
Authors: Mukherjee Kanchan
Published: May 2021

Startups are a reflection of entrepreneurship and innovation in a given country context and have the potential for new venture creation to generate visible economic, social and political impacts and hence are often the focus of policy initiatives. However, designing such policies is a challenging task since often startups fail. The COVID-19 pandemic crisis has brought the policy focus on healthcare and startups globally and there have been numerous policy initiatives to facilitate healthcare startups. However, there is very limited information on this specific startup sector and its implications for policies. Hence, this study proposes to fill this gap and explores the landscape of healthcare startups in India since the creation of India’s startup policy in 2016. Insights from this study have been used to create a conceptual framework for understanding the nature of gaps and their linkages in the startup lifecycle which has global applicability.
Iron-Palladium Decorated Carbon Nanotubes Achieve Radiosensitization via Reactive Oxygen Species Burst
Authors: Yang Shengnan , Yang Yiling , Yang Yi , Zhao Xiangya , Wang Qian , Li Bing , Dong Ling , Tian Rui , Bao Zhirong
Published: May 2021

Radiotherapy is recommended as a modality for cancer treatment in clinic. However, cancerous cells were resistant to therapeutic irradiation due to its DNA repair. In this work, single-walled carbon nanotubes with unique physical properties of hollow structures and high specific surface area were introduced as carrier for iron-palladium (FePd) to obtain iron-palladium decorated carbon nanotubes (FePd@CNTs). On one hand, FePd nanoparticles possess significant ability in radiosensitization as previously reported. On the other hand, carbon nanotubes offer higher efficiency in crossing biological barriers, inducing the accumulation and retention of FePd nanoparticles within tumor tissue. In order to verify the radiosensitization effect of FePd@CNTs, both in vitro and in vivo experiments were conducted. These experiments showed that the FePd@CNTs exhibited remarkably better radiosensitization effect and more obvious accumulation than FePd NPs, suggesting a potential of FePd@CNTs in radiosensitization.
Reduced Expression of GABAA Receptor Alpha2 Subunit Is Associated With Disinhibition of DYT-THAP1 Dystonia Patient-Derived Striatal Medium Spiny Neurons
Authors: Staege Selma , Kutschenko Anna , Baumann Hauke , Glaß Hannes , Henkel Lisa , Gschwendtberger Thomas , Kalmbach Norman , Klietz Martin , Hermann Andreas , Lohmann Katja , Seibler Philip , Wegner Florian
Published: May 2021

DYT-THAP1 dystonia (formerly DYT6) is an adolescent-onset dystonia characterized by involuntary muscle contractions usually involving the upper body. It is caused by mutations in the gene THAP1 encoding for the transcription factor Thanatos-associated protein (THAP) domain containing apoptosis-associated protein 1 and inherited in an autosomal-dominant manner with reduced penetrance. Alterations in the development of striatal neuronal projections and synaptic function are known from transgenic mice models. To investigate pathogenetic mechanisms, human induced pluripotent stem cell (iPSC)-derived medium spiny neurons (MSNs) from two patients and one family member with reduced penetrance carrying a mutation in the gene THAP1 (c.474delA and c.38G > A) were functionally characterized in comparison to healthy controls. Calcium imaging and quantitative PCR analysis revealed significantly lower Ca2+ amplitudes upon GABA applications and a marked downregulation of the gene encoding the GABAA receptor alpha2 subunit in THAP1 MSNs indicating a decreased GABAergic transmission. Whole-cell patch-clamp recordings showed a significantly lower frequency of miniature postsynaptic currents (mPSCs), whereas the frequency of spontaneous action potentials (APs) was elevated in THAP1 MSNs suggesting that decreased synaptic activity might have resulted in enhanced generation of APs. Our molecular and functional data indicate that a reduced expression of GABAA receptor alpha2 subunit could eventually lead to limited GABAergic synaptic transmission, neuronal disinhibition, and hyperexcitability of THAP1 MSNs. These data give pathophysiological insight and may contribute to the development of novel treatment strategies for DYT-THAP1 dystonia.
Accurate Prediction of Prognosis by Integrating Clinical and Molecular Characteristics in Colon Cancer
Authors: Wang Liru , Su Mu , Zhang Mengyan , Zhao Hongyan , Wang Hongli , Xing Jie , Guo Chenyu , Zhou Dianshuang , Xue Wenhui , Lu Haibo , Zhang Yan
Published: May 2021

Various factors affect the prognosis of patients with colon cancer. Complicated factors are found to be conducive to accurate assessment of prognosis. In this study, we developed a series of prognostic prediction models for survival time of colon cancer patients after surgery. Analysis of nine clinical characteristics showed that the most important factor was the positive lymph node ratio (LNR). High LNR was the most important clinical factor affecting 1- and 3-year survival; M0&age < 70 was the most important feature for 5 years. The performance of the model was improved through the integration of clinical characteristics and four types of molecule features (mRNA, lncRNA, miRNA, DNA methylation). The model provides guidance for clinical practice. According to the high-risk molecular features combined with age ≥ 70&T3, poorly differentiated or undifferentiated, M0&well differentiated, M0&T2, LNR high, T4&poorly differentiated, or undifferentiated, the survival time may be less than 1 year; for patients with high risk of molecular features combined with M0&T2, M0&T4, LNR 0& M0, LNR median &T3, and LNR high, the survival is predicted less than 3 years; and the survival of patients with M1&T3, M0 and high risk molecular features is less than 5 years. Using multidimensional and complex patient information, this study establishes potential criteria for clinicians to evaluate the survival of patients for colon cancer.
Von Willebrand Factor Facilitates Intravascular Dissemination of Microsporidia Encephalitozoon hellem
Authors: Bao Jialing , Mo Biying , An Guozhen , Luo Jian , Poncz Mortimer , Pan Guoqing , Li Tian , Zhou Zeyang
Published: May 2021

Microsporidia are a group of spore-forming, fungus-related pathogens that can infect both invertebrates and vertebrates including humans. The primary infection site is usually digestive tract, but systemic infections occur as well and cause damages to organs such as lung, brain, and liver. The systemic spread of microsporidia may be intravascular, requiring attachment and colonization in the presence of shear stress. Von Willebrand Factor (VWF) is a large multimeric intravascular protein and the key attachment sites for platelets and coagulation factors. Here in this study, we investigated the interactions between VWF and microsporidia Encephalitozoon hellem (E. hellem), and the modulating effects on E. hellem after VWF binding. Microfluidic assays showed that E. hellem binds to ultra-large VWF strings under shear stress. In vitro germination assay and infection assay proved that E. hellem significantly increased the rates of germination and infection, and these effects would be reversed by VWF blocking antibody. Mass spectrometry analysis further revealed that VWF-incubation altered various aspects of E. hellem including metabolic activity, levels of structural molecules, and protein maturation. Our findings demonstrated that VWF can bind microsporidia in circulation, and modulate its pathogenicity, including promoting germination and infection rate. VWF facilitates microsporidia intravascular spreading and systemic infection.
A Changing Climate for Knowledge Generation in Agriculture: Lessons to Institutionalize Science-Policy Engagement
Authors: Dinesh Dhanush , Hegger Dries L. T. , Vervoort Joost M. , Driessen Peter P. J.
Published: May 2021

Effective science-policy engagement efforts are crucial to accelerate climate action. Such efforts should be underpinned by high-quality knowledge generation that enhances salience, credibility and legitimacy of research results. This is particularly important for the agricultural sector. Agriculture has been identified as a priority for climate action. The sector also constitutes well-established institutions set up to help achieve food and nutrition security. Institutionalizing high quality knowledge generation for climate change adaptation within these institutions presents a major opportunity to catalyze climate action within the sector. To contribute to insights about this institutionalization, we draw on and develop Cash et al.'s 2002 success conditions for enhancing salience, credibility and legitimacy: (1) increased accountability, (2) use of boundary objects, (3) participation across the boundary, (4) mediation and a selectively permeable boundary, (5) translation, and (6) coordination and complementary expertise. We examine how these success conditions apply in a major global case of agricultural research for development under climate change: the CGIAR Research Program on Climate Change, Agriculture and Food Security (CCAFS). We explore these success conditions in the wider context of CGIAR reform and response to climate change as the international system for Agricultural Research for Development (AR4D). Our results specify and confirm the practical relevance of the six success conditions for institutional design and reform, but also point to the need to complement these with two inductively-derived success conditions: effective leadership and presence of incentives. To institutionalize these success conditions among AR4D institutions, there is an urgent need to create a conducive environment that enables the development of context-specific science-policy engagement strategies, along with leadership development and efforts to break traditional disciplinary silos which constrain user-oriented knowledge production.
Carnistic Colonialism: A Rhetorical Dissection of “Bushmeat” in the 2014 Ebola Outbreak
Authors: Muller S. Marek
Published: May 2021

This article argues that a fusion of critical animal studies and postcolonial critique affords food systems scholars a richer understanding of Western media narratives regarding a “bushmeat problem” during the 2014 Ebola outbreak. To do so, I perform a rhetorical analysis of expert, journalistic, and editorial texts disseminated through outlets with high economic and/or social capital in North American and Western European countries. My analysis demonstrates three overarching themes in these texts regarding the intersections of bushmeat and Ebola, which I describe as: 1) biosecurity; 2) conservation; and 3) development. By invoking an ethic of anti-speciesism and decoloniality, I not only demonstrate the colonial logics at play in the 2014 Ebola outbreak, but also name an insidious ideology fundamental to food systems discourse in postcolonial contexts: carnistic colonialism.
A Neonatal Mouse Model for Pressure Overload: Myocardial Response Corresponds to Severity
Authors: Gu Jielei , Chen Xuke , Jin Yangshuo , Liu Mingke , Xu Qiong , Liu Xiaolin , Luo Zhenyu , Ling Sisi , Liu Ningning , Liu Shiming
Published: May 2021

The heart regeneration after apical resection and myocardial infarction in neonatal mice has been studied for years. However, the response of neonatal mouse heart under pressure overload is seldom explored. This study aimed to induce pressure overload in neonatal mice through a transverse aortic constriction (TAC) with different-gauge needles so as to investigate the effect of pressure overload on cardiomyocyte proliferation and hypertrophy in these mice. Myocardial hypertrophy was evaluated by echocardiographic, pathological, and molecular analyses. Cardiomyocyte proliferation was detected by immune-staining of phospho-histone H3, Ki67, and 5-bromo-2-deoxyuridine. Mild pressure overload induced with a 30-gauge needle stimulated cardiomyocyte proliferation, adaptive hypertrophy, and angiogenesis. The heart function was not hampered even 21 days after the surgery. Moderate pressure overload induced with a 32-gauge needle led to pathological myocardial hypertrophy, fibrosis, and heart failure 7 days after the surgery. The gene and protein expression levels of markers of hypertrophy and fibrosis increased in 32-gauge TAC group compared with that in sham and 30-gauge TAC groups. The mice barely survived after severe pressure overload induced with a 34-gauge needle. The findings of this study might provide new insights into cardiomyocyte proliferation and hypertrophy in neonatal mice under pressure overload.
Sirt3 Protects Against Thoracic Aortic Dissection Formation by Reducing Reactive Oxygen Species, Vascular Inflammation, and Apoptosis of Smooth Muscle Cells
Authors: Qiu Lin , Yi Shaolei , Yu Tingting , Hao Yan
Published: May 2021

Sirtuin3 (Sirt3) is a histone deacetylase involved in the regulation of many cellular processes. Sirt3 deficiency is known to increase oxidative stress. Reactive oxygen species (ROS) promote degradation of the extracellular matrix and vascular smooth muscle cell (VSMC) apoptosis. Reducing oxidative stress by Sirt3 overexpression could have therapeutic potential for limiting thoracic aortic dissection (TAD) development. We hypothesized that Sirt3 deficiency could increase the risk for TAD by decreasing ROS elimination and that Sirt3 overexpression (Sirt3OE) could provide an alternative option for TAD treatment. Mice with TAD had significantly lower Sirt3 expression than normal subjects. Sirt3 KO mice exhibit significantly increased TAD incidence rate and increased aortic diameters. Moreover, Sirt3 overexpression reduced Ang II-induced ROS production, NF-kB activation, and apoptosis in human aortic smooth muscle cells (HASMCs). Sirt3 overexpression attenuated aneurysm formation and decreased aortic expansion. In conclusion, our data showed that Sirt3 deficiency increases susceptibility to TAD formation by attenuating anti-ROS effects and increasing VSMC apoptosis and vascular inflammation.
Epigenetic Changes Associated With Exposure to Glyphosate-Based Herbicides in Mammals
Authors: Rossetti María Florencia , Canesini Guillermina , Lorenz Virginia , Milesi María Mercedes , Varayoud Jorgelina , Ramos Jorge Guillermo
Published: May 2021

Glyphosate is a phosphonomethyl amino acid derivative present in a number of non-selective and systemic herbicides. During the last years the use of glyphosate-based herbicide (GBH) has been increasing exponentially around the world, including Argentina. This fact added to the detection of glyphosate, and its main metabolite, amino methylphosphonic acid (AMPA), in environmental matrices such as soil, sediments, and food, has generated great concern about its risks for humans, animals, and environment. During the last years, there were controversy and intense debate regarding the toxicological effects of these compounds associated with the endocrine system, cancer, reproduction, and development. The mechanisms of action of GBH and their metabolites are still under investigation, although recent findings have shown that they could comprise epigenetic modifications. These are reversible mechanisms linked to tissue-specific silencing of gene expression, genomic imprinting, and tumor growth. Particularly, glyphosate, GBH, and AMPA have been reported to produce changes in global DNA methylation, methylation of specific genes, histone modification, and differential expression of non-coding RNAs in human cells and rodents. Importantly, the epigenome could be heritable and could lead to disease long after the exposure has ended. This mini-review summarizes the epigenetic changes produced by glyphosate, GBHs, and AMPA in humans and rodents and proposes it as a potential mechanism of action through which these chemical compounds could alter body functions.
Neurological Characteristics of Pediatric Glycogen Storage Disease
Authors: Muzetti Julio Henrique , do Valle Daniel Almeida , Santos Mara L. S. Ferreira , Telles Bruno Augusto , Cordeiro Mara L.
Published: May 2021

Glycogen storage diseases (GSD) encompass a group of rare inherited diseases due dysfunction of glycogen metabolism. Hypoglycemia is the most common primary manifestation of GSD, and disturbances in glucose metabolism can cause neurological damage. The aims of this study were to first investigate the metabolic, genetic, and neurological profiles of children with GSD, and to test the hypothesis whether GSD type I would have greater neurological impact than GSD type IX. A cross-sectional study was conducted with 12 children diagnosed with GSD [Types: Ia (n=5); 1, Ib (n=1); 4, IXa (n=5); and 1, IXb (n=1)]. Genetic testing was conducted for the following genes using multigene panel analysis. The biochemical data and magnetic resonance imaging of the brain presented by the patients were evaluated. The criteria of adequate metabolic control were adopted based on the European Study on Glycogen Storage Disease type I consensus. Pathogenic mutations were identified using multigene panel analyses. The mutations and clinical chronology were related to the disease course and neuroimaging findings. Adequate metabolic control was achieved in 67% of patients (GSD I, 43%; GSD IX, 100%). Fourteen different mutations were detected, and only two co-occurring mutations were observed across families (G6PC c.247C>T and c.1039C>T). Six previously unreported variants were identified (5 PHKA2; 1 PHKB). The proportion of GSD IX was higher in our cohort compared to other studies. Brain imaging abnormalities were more frequent among patients with GSD I, early-symptom onset, longer hospitalization, and inadequate metabolic control. The frequency of mutations was similar to that observed among the North American and European populations. None of the mutations observed in PHKA2 have been described previously. Therefore, current study reports six GSD variants previously unknown, and neurological consequences of GSD I. The principal neurological impact of GSD appeared to be related to inadequate metabolic control, especially hypoglycemia.
The Significance of Genotypic Diversity in Coral Competitive Interaction: A Transcriptomic Perspective
Authors: Andrade Rodriguez N. , Moya A. , Jones R. , Miller D. J. , Cooke I. R.
Published: May 2021

Competitive interactions shape coral assemblages and govern the dynamics of coral ecosystems. Although competition is an ecological concept, the outcomes of competitive interactions are ultimately determined by patterns of gene expression. These patterns are subject to genotypic variation on both sides of any interaction. Such variation is typically treated as “noise”, but it is sometimes possible to identify patterns within it that reveal important hidden factors in an experiment. To incorporate genotypic variation into the investigation of coral competitive interactions, we used RNA-sequencing to study changes in gene expression in a hard coral (Porites cylindrica) resulting from non-contact competition experiment with a soft coral (Lobophytum pauciflorum). Hard coral genotype explained the largest proportion of variation between samples; however, it was also possible to detect gene expression changes in 76 transcripts resulting from interaction with the soft coral. In addition, we found a group of 20 short secreted proteins that were expressed as a coordinated unit in three interacting Porites-Lobophytum pairs. The presence of this secretion response was idiosyncratic in that it could not be predicted based on polyp behaviour, or the genotype of hard or soft coral alone. This study illustrates the significance of individual variation as a determinant of competitive behaviour, and also provides some intriguing glimpses into the molecular mechanisms employed by hard corals competing at a distance.
Galectin-Receptor Interactions Regulates Cardiac Pathology Caused by Trichinella spiralis Infection
Authors: Yan Jinghai , Huang Shiguang , Lu Fangli
Published: May 2021

The parasitic nematode Trichinella spiralis causes trichinellosis, a serious food-borne parasitic zoonosis worldwide. Infection with T. spiralis may also cause myocarditis. In the present study, we used mouse models to assess the impact of blockage of galectin-receptor interactions by α-lactose on cardiac immunopathology during acute T. spiralis experimental infection. Our data demonstrated that, after T. spiralis infection, blockage of galectin-receptor interactions resulted in cardiac dysfunction detected by transthoracic conventional echocardiography, and increased serum Gal-3 level, a biomarker of myocardial damage. In addition, there were increased eosinophil number in peripheral blood, and increased eosinophil infiltration in the heart and spleen tissues accompanied with increased mRNA levels of eosinophil granule proteins (including eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO)) and IL-5 in these organs; increased cardiac fibrosis accompanied with increased Gal-3 and collagen 1 expressions in the hearts of mice with blockage of galectin-receptor interactions after T. spiralis infection. Correlation analysis showed that significant positive correlations existed between the mRNA levels of Gal-3 and ECP/EPO/eosinophil major basic protein/IL-5/CCL11/CCR3/α-SMA/collagen 1 in the hearts of both T. spiralis-infected mice and T. spiralis-infected mice with blockage of galectin-receptor interactions. Our data suggest that galectin-receptor interactions play a pivotal role during acute T. spiralis infection, and lack of galectin-receptor interactions upregulates Gal-3 which, in turn, leads to elevated heart eosinophil recruitment, exacerbated heart pathology and fibrosis, and heart functional damage.
Clinical Utility of Whole Exome Sequencing and Targeted Panels for the Identification of Inborn Errors of Immunity in a Resource-Constrained Setting
Authors: Engelbrecht Clair , Urban Michael , Schoeman Mardelle , Paarwater Brandon , van Coller Ansia , Abraham Deepthi Raju , Cornelissen Helena , Glashoff Richard , Esser Monika , Möller Marlo , Kinnear Craig , Glanzmann Brigitte
Published: May 2021

Primary immunodeficiency disorders (PIDs) are inborn errors of immunity (IEI) that cause immune system impairment. To date, more than 400 single-gene IEI have been well defined. The advent of next generation sequencing (NGS) technologies has improved clinical diagnosis and allowed for discovery of novel genes and variants associated with IEI. Molecular diagnosis provides clear clinical benefits for patients by altering management, enabling access to certain treatments and facilitates genetic counselling. Here we report on an 8-year experience using two different NGS technologies, namely research-based WES and targeted gene panels, in patients with suspected IEI in the South African healthcare system. A total of 52 patients’ had WES only, 26 had a targeted gene panel only, and 2 had both panel and WES. Overall, a molecular diagnosis was achieved in 30% (24/80) of patients. Clinical management was significantly altered in 67% of patients following molecular results. All 24 families with a molecular diagnosis received more accurate genetic counselling and family cascade testing. Results highlight the clinical value of expanded genetic testing in IEI and its relevance to understanding the genetic and clinical spectrum of the IEI-related disorders in Africa. Detection rates under 40% illustrate the complexity and heterogeneity of these disorders, especially in an African population, thus highlighting the need for expanded genomic testing and research to further elucidate this.
Plasma Membrane Calcium ATPase Regulates Stoichiometry of CD4+ T-Cell Compartments
Authors: Merino-Wong Maylin , Niemeyer Barbara A. , Alansary Dalia
Published: May 2021

Immune responses involve mobilization of T cells within naïve and memory compartments. Tightly regulated Ca2+levels are essential for balanced immune outcomes. How Ca2+contributes to regulating compartment stoichiometry is unknown. Here, we show that plasma membrane Ca2+ATPase 4 (PMCA4) is differentially expressed in human CD4+T compartments yielding distinct store operated Ca2+entry (SOCE) profiles. Modulation of PMCA4 yielded a more prominent increase of SOCE in memory than in naïve CD4+T cell. Interestingly, downregulation of PMCA4 reduced the effector compartment fraction and led to accumulation of cells in the naïve compartment.In silicoanalysis and chromatin immunoprecipitation point towards Ying Yang 1 (YY1) as a transcription factor regulating PMCA4 expression. Analyses of PMCA and YY1 expression patterns following activation and of PMCA promoter activity following downregulation of YY1 highlight repressive role of YY1 on PMCA expression. Our findings show that PMCA4 adapts Ca2+levels to cellular requirements during effector and quiescent phases and thereby represent a potential target to intervene with the outcome of the immune response.
PARK7 Protects Against Chronic Kidney Injury and Renal Fibrosis by Inducing SOD2 to Reduce Oxidative Stress
Authors: Yin Lijun , Li Honglin , Liu Zhiwen , Wu Wenwen , Cai Juan , Tang Chengyuan , Dong Zheng
Published: May 2021

Renal fibrosis is the final common pathway to chronic kidney diseases regardless of etiology. Parkinson disease protein 7 (PARK7) is a multifunctional protein involved in various cellular processes, but its pathophysiological role in kidneys remain largely unknown. Here, we have determined the role of PARK7 in renal fibrosis and have further elucidated the underlying mechanisms by using the in vivo mouse model of unilateral ureteric obstruction (UUO) and the in vitro model of transforming growth factor-b (TGFB1) treatment of cultured kidney proximal tubular cells. PARK7 decreased markedly in atrophic kidney tubules in UUO mice, and Park7 deficiency aggravated UUO-induced renal fibrosis, tubular cell apoptosis, ROS production and inflammation. In vitro, TGFB1 treatment induced fibrotic changes in renal tubular cells, which was accompanied by alterations of PARK7. Park7 knockdown exacerbated TGFB1-induced fibrotic changes, cell apoptosis and ROS production, whereas Park7 overexpression or treatment with ND-13 (a PARK7-derived peptide) attenuated these TGFB1-induced changes. Mechanistically, PARK7 translocated into the nucleus of renal tubular cells following TGFB1 treatment or UUO, where it induced the expression of SOD2, an antioxidant enzyme. Taken together, these results indicate that PARK7 protects against chronic kidney injury and renal fibrosis by inducing SOD2 to reduce oxidative stress in tubular cells.
Design and Shape Optimization of a Biodegradable Polymeric Stent for Curved Arteries Using FEM
Authors: Baradaran Yasaman , Baghani Mostafa , Kazempour Morteza , Hosseini Seyed Kianoosh , Karimpour Morad , Baniassadi Majid
Published: May 2021

Stent treatment has revealed safe and efficient outcomes for straight arteries, while it is still challenging for curved coronary arteries. On the one hand, a stent should be flexible enough to take the artery’s curvature with the least stress to the artery wall. On the other hand, it has to be strong enough to prevent any artery diameter reduction after the implant. In this work, the genetic algorithm multi-objective optimization method is exploited to provide a Pareto set and to design a curvature stent. The design has been performed based on the appropriate flexibility and radial strength design, depending on the characteristics of a particular case study. In the optimization procedure, flexibility and radial strength have been evaluated based on ASTM standard mechanical tests. These tests have been parametrically simulated using the finite element method. The strut curvature is formed by the spline curvature, whose middle point coordinates are two of the optimization variables. The other optimization variable is the thickness of the stent. Based on the Pareto set achieved from the optimization, five different stent designs have been proposed. In these designs, the middle part of the stent is stiffer (in the plaque aggregated) and benefits more radial strength rather than flexibility. At the stent’s extremes, where more deformation takes place, flexibility is weighted more than radial strength. These five design sets differ in their objective weight ratios. At the end of this research, their implementation in a curved vessel is simulated in ABAQUS/CAE, and von Mises stress distribution, maximum von Mises stress, and stent recoil after imposing the stent have been analyzed. The obtained Pareto front can also be a useful guide for physicians to design and manufacture customized stents for each patient.
Implementation of Automated Blood Culture With Quality Assurance in a Resource-Limited Setting
Authors: von Laer Anja , N'Guessan Micheline Ahou , Touré Fidèle Sounan , Nowak Kathrin , Groeschner Karin , Ignatius Ralf , Friesen Johannes , Tomczyk Sara , Leendertz Fabian H. , Eckmanns Tim , Akoua-Koffi Chantal
Published: May 2021

Background: Blood cultures (BC) have a high clinical relevance and are a priority specimen for surveillance of antimicrobial resistance. Manual BC are still most frequently used in resource-limited settings. Data on automated BC performance in Africa are scarce. We implemented automated BC at a surveillance site of the African Network for improved Diagnostics, Epidemiology and Management of Common Infectious Agents (ANDEMIA).

Methods: Between June 2017 and January 2018, pairs of automated BC (BacT/ALERT®FA Plus) and manual BC (brain-heart infusion broth) were compared at a University hospital in Bouaké, Côte d'Ivoire. BC were inoculated each with a target blood volume of 10 ml from the same venipuncture. Automated BC were incubated for up to 5 days, manual BC for up to 10 days. Terminal subcultures were performed for manual BC only. The two systems were compared regarding yield, contamination, and turnaround time. For quality assurance, isolates were retested in a German routine microbiological laboratory.

Results: BC sampling was increased from on average 24 BC to 63 BC per month. A total of 337 matched pairs of BC were included. Automated BC was positive in 36.5%, manual BC in 24.0% (p-value < 0.01), proportion of contamination was 47.9 and 43.8%, respectively (p-value = 1.0). Turnaround time of positive BC was shortened by 2.5 days with automated compared to manual BC (p < 0.01). Most common detected pathogens in both systems were Klebsiella spp. (26.0%) and Staphylococcus aureus (18.2%). Most contaminants were members of the skin flora. Retesting of 162 isolates was concordant in 79.6% on family level.

Conclusions: Implementing automated BC in a resource-limited setting is possible and improves microbiological diagnostic performance. Automated BC increased yield and shortened turnaround times. Regular training and mentorship of clinicians has to be intensified to increase number and quality of BC. Pre-analytical training to improve diagnostic stewardship is essential when implementing a new microbiological method. Retesting highlighted that manual identification and antimicrobial susceptibility testing can be of good quality and sustainable. The implementation of automated tools should be decided individually according to economic considerations, number of samples, stable supply chain of consumables, and technical sustainability.
Efficacy of a New Non-drug Acne Therapy: Aloe Vera Gel Combined With Ultrasound and Soft Mask for the Treatment of Mild to Severe Facial Acne
Authors: Zhong Hongyu , Li Xiang , Zhang Wanqi , Shen Xiaoxiao , Lu Yuangang , Li Hongli
Published: May 2021

Background: Acne is a chronic disorder that affects almost 80% of adolescents and young adults, causing psychological and emotional distress. However, the current treatments for acne are either ineffective or have many side effects. This study was designed to confirm and objectively quantify the effect of a new non-drug combined therapy on acne.

Methods: This study innovatively utilized ultrasound, which enhanced the absorption of aloe vera gel, and soft mask to make a purely physical method without any drugs. In both the treatment group and control group, the number of papules/pustules and the area of hyperpigmented lesions were counted, and a smart mirror intelligent face system was used before and after the combined therapy. Alterations in the skin functional index were recorded and analyzed statistically.

Results: In the treatment group, the combined therapy significantly reduced the number of papules and the area of hyperpigmented lesions and improved skin roughness and local blood circulation. In the control group, there was no obvious improvement over 2 months.

Conclusion: This study suggests that the new non-drug combined therapy significantly improved acne, which provided experimental evidence and treatment guidance for patients with mild to severe acne, especially patients with moderate acne. This new therapy may possibly be an appropriate method for patients who seek topical treatments with mild side effects and low antibiotic resistance rates.
Compartmentalized Reconstitution of Post-squalene Pathway for 7-Dehydrocholesterol Overproduction in Saccharomyces cerevisiae
Authors: Guo Xiao-Jing , Yao Ming-Dong , Xiao Wen-Hai , Wang Ying , Zhao Guang-Rong , Yuan Ying-Jin
Published: May 2021

7-Dehydrocholesterol (7-DHC) is the direct precursor to manufacture vitamin D3. Our previous study has achieved 7-DHC synthesis in Saccharomyces cerevisiae based on the endogenous post-squalene pathway. However, the distribution of post-squalene enzymes between the endoplasmic reticulum (ER) and lipid bodies (LD) might raise difficulties for ERG proteins to catalyze and deliver sterol intermediates, resulting in unbalanced metabolic flow and low product yield. Herein, we intended to rearrange the subcellular location of post-squalene enzymes to alleviate metabolic bottleneck and boost 7-DHC production. After identifying the location of DHCR24 (C-24 reductase, the only heterologous protein for 7-DHC biosynthesis) on ER, all the ER-located enzymes were grouped into four modules: ERG1/11/24, ERG25/26/27, ERG2/3, and DHCR24. These modules attempted to be overexpressed either on ER or on LDs. As a result, expression of LD-targeted DHCR24 and ER-located ERG1/11/24 could promote the conversion efficiency among the sterol intermediates to 7-DHC, while locating module ERG2/3 into LDs improved the whole metabolic flux of the post-squalene pathway. Coexpressing LD-targeted ERG2/3 and DHCR24 (generating strain SyBE_Sc01250035) improved 7-DHC production from 187.7 to 308.2 mg/L at shake-flask level. Further expressing ER-targeted module ERG1/11/24 in strain SyBE_Sc01250035 dramatically reduced squalene accumulation from 620.2 mg/L to the lowest level (by 93.8%) as well as improved 7-DHC production to the highest level (to 342.2 mg/L). Then targeting module ERG25/26/27 to LDs further increased 7-DHC titer to 360.6 mg/L, which is the highest shake-flask level production for 7-DHC ever reported. Our study not only proposes and further proves the concept of pathway compartmentalized reconstitution to regulate metabolic flux but also provides a promising chassis to produce other steroidal compounds through the post-squalene pathway.