bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth Factor Deregulation and Emerging Role of Phosphatases in Diabetic Peripheral Artery Disease
Authors: Mercier Clément , Rousseau Marina , Geraldes Pedro
Published: January 2021

Peripheral artery disease is caused by atherosclerosis of lower extremity arteries leading to the loss of blood perfusion and subsequent critical ischemia. The presence of diabetes mellitus is an important risk factor that greatly increases the incidence, the progression and the severity of the disease. In addition to accelerated disease progression, diabetic patients are also more susceptible to develop serious impairment of their walking abilities through an increased risk of lower limb amputation. Hyperglycemia is known to alter the physiological development of collateral arteries in response to ischemia. Deregulation in the production of several critical pro-angiogenic factors has been reported in diabetes along with vascular cell unresponsiveness in initiating angiogenic processes. Among the multiple molecular mechanisms involved in the angiogenic response, protein tyrosine phosphatases are potent regulators by dephosphorylating pro-angiogenic tyrosine kinase receptors. However, evidence has indicated that diabetes-induced deregulation of phosphatases contributes to the progression of several micro and macrovascular complications. This review provides an overview of growth factor alterations in the context of diabetes and peripheral artery disease, as well as a description of the role of phosphatases in the regulation of angiogenic pathways followed by an analysis of the effects of hyperglycemia on the modulation of protein tyrosine phosphatase expression and activity. Knowledge of the role of phosphatases in diabetic peripheral artery disease will help the development of future therapeutics to locally regulate phosphatases and improve angiogenesis.
Spatiotemporal Dynamics of 20th-Century Spruce Budworm Outbreaks in Eastern Canada: Three Distinct Patterns of Outbreak Severity
Authors: Berguet Cassy , Martin Maxence , Arseneault Dominique , Morin Hubert
Published: January 2021

Spruce budworm (SBW) outbreaks are a major disturbance in North American forests. In Quebec, Canada, the recent history of SBW outbreaks at the local scale is well-known. Studies at the Québec scale nonetheless remain rare despite the need to better understand the dynamics of SBW outbreaks at a larger scale. This study aimed to reconstruct the spatiotemporal dynamics of SBW outbreaks during the 20th century across the insect's range in southern Quebec. To this end, we sampled 83 stands throughout southern Quebec. These stands were selected according to their age and the presence of black, white, and red spruce. In fact, spruce, unlike balsam fir, survives the SBW outbreaks and can record them in these growth rings. In each stand, cores were taken from 20 spruce trees. The dendrochronological series of more than 1,600 trees were analyzed, and we identified, through the k-means grouping of stands, the spatial patterns of tree growth for the three previously documented 20th century SBW outbreaks. The outbreaks were not homogeneous across the distribution range of the insect. Two groups of stands showed early- (1905–1930) and late-century (1968–1988) outbreaks of high severity and a mid-century (1935–1965) outbreak of moderate severity. This pattern is explained mainly by the presence of the insect within the balsam fir–yellow birch and balsam fir–white birch bioclimatic domains, areas where outbreaks tend to be most severe because of the abundance of balsam fir, the main SBW host species. However, these two models differ in terms of the duration of outbreaks. A third, more northern, cluster of stands experienced lower severity outbreaks over the 20th century, a pattern explained by a lower proportion of balsam fir trees in these landscapes. Our study shows that, on the one hand, these three groups of stands are defined by outbreaks of specific duration (an outbreak period beginning when more than 20% of the trees are affected and ending when <20% of the trees are affected) and severity (in terms of percentage of affected trees), and on the other hand they are spatially distinct and subject to different climatic conditions.
Strontium and Oxygen Isotope Analyses Reveal Late Cretaceous Shark Teeth in Iron Age Strata in the Southern Levant
Authors: Tütken Thomas , Weber Michael , Zohar Irit , Helmy Hassan , Bourgon Nicolas , Lernau Omri , Jochum Klaus Peter , Sisma-Ventura Guy
Published: January 2021

Skeletal remains in archaeological strata are often assumed to be of similar ages. Here we show that combined Sr and O isotope analyses can serve as a powerful tool for assessing fish provenance and even for identifying fossil fish teeth in archaeological contexts. For this purpose, we established a reference Sr and O isotope dataset of extant fish teeth from major water bodies in the Southern Levant. Fossil shark teeth were identified within Iron Age cultural layers dating to 8–9th century BCE in the City of David, Jerusalem, although the reason for their presence remains unclear. Their enameloid 87Sr/86Sr and δ18OPO4 values [0.7075 ± 0.0001 (1 SD, n = 7) and 19.6 ± 0.9‰ (1 SD, n = 6), respectively], are both much lower than values typical for modern marine sharks from the Mediterranean Sea [0.7092 and 22.5–24.6‰ (n = 2), respectively]. The sharks’ 87Sr/86Sr are also lower than those of rain- and groundwater as well as the main soil types in central Israel (≥0.7079). This indicates that these fossil sharks incorporated Sr (87Sr/86Sr ≈ 0.7075) from a marine habitat with values typical for Late Cretaceous seawater. This scenario is in line with the low shark enameloid δ18OPO4 values reflecting tooth formation in the warm tropical seawater of the Tethys Ocean. Age estimates using 87Sr/86Sr stratigraphy place these fossil shark teeth at around 80-million-years-old. This was further supported by their taxonomy and the high dentine apatite crystallinity, low organic carbon, high U and Nd contents, characteristics that are typical for fossil specimens, and different from those of archaeological Gilthead seabream (Sparus aurata) teeth from the same cultural layers and another Chalcolithic site (Gilat). Chalcolithic and Iron Age seabream enameloid has seawater-like 87Sr/86Sr of 0.7091 ± 0.0001 (1 SD, n = 6), as expected for modern marine fish. Fossil shark and archaeological Gilthead seabream teeth both preserve original, distinct enameloid 87Sr/86Sr and δ18OPO4 signatures reflecting their different aquatic habitats. Fifty percent of the analysed Gilthead seabream teeth derive from hypersaline seawater, indicating that these seabreams were exported from the hypersaline Bardawil Lagoon in Sinai (Egypt) to the Southern Levant since the Iron Age period and possibly even earlier.
Consistent Behavioral Syndrome Across Seasons in an Invasive Freshwater Fish
Authors: Lukas Juliane , Kalinkat Gregor , Miesen Friedrich Wilhelm , Landgraf Tim , Krause Jens , Bierbach David
Published: January 2021

Understanding the linkage between behavioral types and dispersal tendency has become a pressing issue in light of global change and biological invasions. Here, we explore whether dispersing individuals exhibit behavioral types that differ from those remaining in the source population. We investigated a feral population of guppies (Poecilia reticulata) that undergoes a yearly range shift cycle. Guppies are among the most widespread invasive species in the world, but in temperate regions these tropical fish can only survive in winter-warm freshwaters. Established in a thermally-altered stream in Germany, guppies are confined to a warm-water influx in winter, but can spread to peripheral parts as these become thermally accessible. We sampled fish from the source population and a winter-abandoned site in March, June and August. Fish were tested for boldness, sociability and activity involving open-field tests including interactions with a robotic social partner. Guppies differed consistently among each other in all three traits within each sample. Average trait expression in the source population differed across seasons, however, we could not detect differences between source and downstream population. Instead, all populations exhibited a remarkably stable behavioral syndrome between boldness and activity despite strong seasonal changes in water temperature and associated environmental factors. We conclude that random drift (opposed to personality-biased dispersal) is a more likely dispersal mode for guppies, at least in the investigated stream. In the face of fluctuating environments, guppies seem to be extremely effective in keeping behavioral expressions constant, which could help explain their successful invasion and adaptation to new and disturbed habitats.
Familial Hypercholesterolemia in Russia: Three Decades of Genetic Studies
Authors: Vasilyev Vadim , Zakharova Faina , Bogoslovskay Tatiana , Mandelshtam Mikhail
Published: January 2021

The first studies of familial hypercholesterolemia (FH) in Russia go back to late 1980-ies. For more than 10 years the research in this field was carried out in Saint-Petersburg, the megapolis in the North-West Russia. Studies were focused on the search for causative mutations in low-density lipoprotein receptor gene (LDLR). Gradually the research was spread to Petrozavodsk in Karelia and in the XXI century two more centers contributed in investigations of genetics of FH, i.e., in Moscow and Novosibirsk. The best studied is the spectrum of mutations in LDLR, though genetic abnormalities in APOB and PCSK9 genes were also considered. Despite that some 40% mutations in LDLR found in Saint-Petersburg and Moscow are referred to as specific for Russian population, and this proportion is even higher in Karelia (ca. 70%), rapid introduction of NGS and intensifying genetic research all over the world result in continuous decrease of these numbers as “Slavic” mutations become documented in other countries. The samplings of genetically characterized patients in Russia were relatively small, which makes difficult to specify major mutations reflecting the national specificity of FH. Moreover, the majority of studies accomplished so far did not explore possible associations of certain mutations with ethnic origin of patients. By now the only exception is the study of Karelian population showing the absence of typical Finnish mutations in the region that borders on Finland. It can be concluded that the important primary research partly characterizing the mutation spectrum in FH patients both in the European and Siberian parts of Russia has been done. However, it seems likely that the most interesting and comprehensive genetic studies of FH in Russia, concerning various mutations in different genes and the variety of ethnic groups in this multi-national country, are still to be undertaken.
Comparative and Functional Analyses of Two Sequenced Paenibacillus polymyxa Genomes Provides Insights Into Their Potential Genes Related to Plant Growth-Promoting Features and Biocontrol Mechanisms
Authors: Li Jin-Yi , Gao Tan-Tan , Wang Qi
Published: January 2021

Many bacteria belonging to Paenibacillus polymyxa are plant growth-promoting rhizobacteria (PGPR) with the potential to promote plant growth and suppress phytopathogens and have been used as biological control agents (BCAs). However, the growth promotion and biocontrol mechanisms of P. polymyxa have not been thoroughly elucidated thus far. In this investigation, the genome sequences of two P. polymyxa strains, ZF129 and ZF197, with broad anti-pathogen activities and potential for growth promotion were comparatively studied. Comparative and functional analyses of the two sequenced P. polymyxa genomes showed that the ZF129 genome consists of one 5,703,931 bp circular chromosome and two 79,020 bp and 37,602 bp plasmids, designated pAP1 and pAP2, respectively. The complete genome sequence of ZF197 consists of one 5,507,169 bp circular chromosome and one 32,065 bp plasmid, designated pAP197. Phylogenetic analysis revealed that ZF129 is highly similar to two P. polymyxa strains, HY96-2 and SQR-21, while ZF197 is highly similar to P. polymyxa strain J. The genes responsible for secondary metabolite synthesis, plant growth-promoting traits, and systemic resistance inducer production were compared between strains ZF129 and ZF197 as well as other P. polymyxa strains. The results indicated that the variation of the corresponding genes or gene clusters between strains ZF129 and ZF197 may lead to different antagonistic activities of their volatiles or cell-free supernatants against Fusarium oxysporum. This work indicates that plant growth promotion by P. polymyxa is largely mediated by phytohormone production, increased nutrient availability and biocontrol mechanisms. This study provides an in-depth understanding of the genome architecture of P. polymyxa, revealing great potential for the application of this bacterium in the fields of agriculture and horticulture as a PGPR.
Estimation of Heterogeneous Restricted Mean Survival Time Using Random Forest
Authors: Liu Mingyang , Li Hongzhe
Published: January 2021

Estimation and prediction of heterogeneous restricted mean survival time (hRMST) is of great clinical importance, which can provide an easily interpretable and clinically meaningful summary of the survival function in the presence of censoring and individual covariates. The existing methods for the modeling of hRMST rely on proportional hazards or other parametric assumptions on the survival distribution. In this paper, we propose a random forest based estimation of hRMST for right-censored survival data with covariates and prove a central limit theorem for the resulting estimator. In addition, we present a computationally efficient construction for the confidence interval of hRMST. Our simulations show that the resulting confidence intervals have the correct coverage probability of the hRMST, and the random forest based estimate of hRMST has smaller prediction errors than the parametric models when the models are mis-specified. We apply the method to the ovarian cancer data set from The Cancer Genome Atlas (TCGA) project to predict hRMST and show an improved prediction performance over the existing methods. A software implementation, srf using R and C++, is available at https://github.com/lmy1019/SRF.
Periostin Contributes to Immunoglobulin a Nephropathy by Promoting the Proliferation of Mesangial Cells: A Weighted Gene Correlation Network Analysis
Authors: Wu Jingkui , Lin Qisheng , Li Shu , Shao Xinghua , Zhu Xuying , Zhang Minfang , Zhou Wenyan , Ni Zhaohui
Published: January 2021

Immunoglobulin A nephropathy (IgAN) is a known cause of end-stage kidney disease, but the pathogenesis and factors affecting prognosis are not fully understood. In the present study, we carried out weighted gene correlation network analysis (WGCNA) to identify hub genes related to the occurrence of IgAN and validated candidate genes in experiments using mouse mesangial cells (MMCs) and clinical specimens (kidney tissue from IgAN patients and healthy controls). We screened the GSE37460 and GSE104948 differentially expressed genes common to both datasets and identified periostin (POSTN) as one of the five key genes using the cytoHubba plugin of Cytoscape software and by receiver-operating characteristic curve analysis. The top 25% of genes in the GSE93798 dataset showing variable expression between IgAN and healthy tissue were assessed by WGCNA. The royalblue module in WGCNA was closely related to creatinine and estimated glomerular filtration rate (eGFR) in IgAN patients.POSTNhad very high module membership and gene significance values for creatinine (0.82 and 0.66, respectively) and eGFR (0.82 and −0.67, respectively), indicating that it is a co-hub gene. In MMCs,POSTNwas upregulated by transforming growth factor β1, and stimulation of MMCs with recombinant POSTN protein resulted in an increase in the level of proliferating cell nuclear antigen (PCNA) and a decrease in that of B cell lymphoma-associated X protein, which were accompanied by enhanced MMC proliferation.POSTNgene knockdown had the opposite effects. Immunohistochemical analysis of kidney tissue specimens showed that POSTN and PCNA levels were elevated, whereas the rate of apoptosis was reduced in IgAN patients relative to healthy controls. POSTN level in the kidney tissue of IgAN patients was positively correlated with creatinine level and negatively correlated with eGFR. Thus, POSTN promotes the proliferation of MCs to promote renal dysfunction in IgAN.
Epstein-Barr Virus and Systemic Autoimmune Diseases
Authors: Houen Gunnar , Trier Nicole Hartwig
Published: January 2021

Epstein-Barr Virus (EBV) is an extremely successful human herpes virus, which infects essentially all human beings at some time during their life span. EBV infection and the associated immune response results in production of antibodies (seroconversion), which occurs mainly during the first years of life, but may also happen during adolescence or later in life. Infection of adolescents can result in infectious mononucleosis, an acute serious condition characterized by massive lymphocytosis. Transmission of EBV mainly occurs through saliva but can rarely be spread through semen or blood, e.g. through organ transplantations and blood transfusions. EBV transmission through oral secretions results in infection of epithelial cells of the oropharynx. From the epithelial cells EBV can infect B cells, which are the major reservoir for the virus, but other cell types may also become infected. As a result, EBV can shuttle between different cell types, mainly B cells and epithelial cells. Moreover, since the virus can switch between a latent and a lytic life cycle, EBV has the ability to cause chronic relapsing/reactivating infections. Chronic or recurrent EBV infection of epithelial cells has been linked to systemic lupus erythematosus and Sjögren’s syndrome, whereas chronic/recurrent infection of B cells has been associated with rheumatoid arthritis, multiple sclerosis and other diseases. Accordingly, since EBV can shuttle between epithelial cells and B cells, the systemic autoimmune diseases often occur as overlapping syndromes with symptoms and characteristic autoantibodies (e.g. antinuclear antibodies and rheumatoid factors) reflecting epithelial and/or B cell infection.
Factor H Autoantibodies and Complement-Mediated Diseases
Authors: Zhang Yuzhou , Ghiringhelli Borsa Nicolo , Shao Dingwu , Dopler Arthur , Jones Michael B. , Meyer Nicole C. , Pitcher Gabriella R. , Taylor Amanda O. , Nester Carla M. , Schmidt Christoph Q. , Smith Richard J. H.
Published: January 2021

Factor H (FH), a member of the regulators-of-complement-activation (RCA) family of proteins, circulates in human plasma at concentrations of 180–420 mg/L where it controls the alternative pathway (AP) of complement in the fluid phase and on cell surfaces. When the regulatory function of FH is impaired, complement-mediated tissue injury and inflammation occur, leading to diseases such as atypical hemolytic uremic syndrome (a thrombotic microangiopathy or TMA), C3 glomerulopathy (C3G) and monoclonal gammopathy of renal significance (MGRS). A pathophysiological cause of compromised FH function is the development of autoantibodies to various domains of the FH protein. FH autoantibodies (FHAAs) are identified in 10.9% of patients with aHUS, 3.2% of patients with C3G, and rarely in patients with MGRS. The phenotypic variability of FHAA-mediated disease reflects both the complexity of FH and the epitope specificity of FHAA for select regions of the native protein. In this paper, we have characterized FHAA epitopes in a large cohort of patients diagnosed with TMA, C3G or MGRS. We explore the epitopes recognized by FHAAs in these diseases and the association of FHAAs with the genetic deletion of both copies of the CFHR1 gene to show how these disease phenotypes are associated with this diverse spectrum of autoantibodies.
Targeted De-Methylation of the FOXP3-TSDR Is Sufficient to Induce Physiological FOXP3 Expression but Not a Functional Treg Phenotype
Authors: Kressler Christopher , Gasparoni Gilles , Nordström Karl , Hamo Dania , Salhab Abdulrahman , Dimitropoulos Christoforos , Tierling Sascha , Reinke Petra , Volk Hans-Dieter , Walter Jörn , Hamann Alf , Polansky Julia K.
Published: January 2021

CD4+ regulatory T cells (Tregs) are key mediators of immunological tolerance and promising effector cells for immuno-suppressive adoptive cellular therapy to fight autoimmunity and chronic inflammation. Their functional stability is critical for their clinical utility and has been correlated to the demethylated state of the TSDR/CNS2 enhancer element in the Treg lineage transcription factor FOXP3. However, proof for a causal contribution of the TSDR de-methylation to FOXP3 stability and Treg induction is so far lacking. We here established a powerful transient-transfection CRISPR-Cas9-based epigenetic editing method for the selective de-methylation of the TSDR within the endogenous chromatin environment of a living cell. The induced de-methylated state was stable over weeks in clonal T cell proliferation cultures even after expression of the editing complex had ceased. Epigenetic editing of the TSDR resulted in FOXP3 expression, even in its physiological isoform distribution, proving a causal role for the de-methylated TSDR in FOXP3 regulation. However, successful FOXP3 induction was not associated with a switch towards a functional Treg phenotype, in contrast to what has been reported from FOXP3 overexpression approaches. Thus, TSDR de-methylation is required, but not sufficient for a stable Treg phenotype induction. Therefore, targeted demethylation of the TSDR may be a critical addition to publishedin vitroTreg induction protocols which so far lack FOXP3 stability.
Case Report: An EGFR-Targeted 4-1BB-agonistic Trimerbody Does Not Induce Hepatotoxicity in Transgenic Mice With Liver Expression of Human EGFR
Authors: Compte Marta , Harwood Seandean L. , Martínez-Torrecuadrada Jorge , Perez-Chacon Gema , González-García Patricia , Tapia-Galisteo Antonio , Van Bergen en Henegouwen Paul M. P. , Sánchez Aránzazu , Fabregat Isabel , Sanz Laura , Zapata Juan M. , Alvarez-Vallina Luis
Published: January 2021

Agonistic monoclonal antibodies (mAbs) targeting the co-stimulatory receptor 4-1BB are among the most effective immunotherapeutic agents across pre-clinical cancer models. However, clinical development of full-length 4-1BB agonistic mAbs, has been hampered by dose-limiting liver toxicity. We have previously developed an EGFR-targeted 4-1BB-agonistic trimerbody (1D8N/CEGa1) that induces potent anti-tumor immunity without systemic toxicity, in immunocompetent mice bearing murine colorectal carcinoma cells expressing human EGFR. Here, we study the impact of human EGFR expression on mouse liver in the toxicity profile of 1D8N/CEGa1. Systemic administration of IgG-based anti-4-1BB agonist resulted in nonspecific immune stimulation and hepatotoxicity in a liver-specific human EGFR-transgenic immunocompetent mouse, whereas in 1D8N/CEGa1-treated mice no such immune-related adverse effects were observed. Collectively, these data support the role of FcγR interactions in the major off-tumor toxicities associated with IgG-based 4-1BB agonists and further validate the safety profile of EGFR-targeted Fc-less 4-1BB-agonistic trimerbodies in systemic cancer immunotherapy protocols.
Targeting the FcεRI Pathway as a Potential Strategy to Prevent Food-Induced Anaphylaxis
Authors: Dispenza Melanie C. , Bochner Bruce S. , MacGlashan Donald W.
Published: January 2021

Despite attempts to halt it, the prevalence of food allergy is increasing, and there is an unmet need for strategies to prevent morbidity and mortality from food-induced allergic reactions. There are no known medications that can prevent anaphylaxis, but several novel therapies show promise for the prevention of food-induced anaphylaxis through targeting of the high-affinity IgE receptor (FcϵRI) pathway. This pathway includes multiple candidate targets, including tyrosine kinases and the receptor itself. Small molecule inhibitors of essential kinases have rapid onset of action and transient efficacy, which may be beneficial for short-term use for immunotherapy buildup or desensitizations. Short courses of FDA-approved inhibitors of Bruton’s tyrosine kinase can eliminate IgE-mediated basophil activation and reduce food skin test size in allergic adults, and prevent IgE-mediated anaphylaxis in humanized mice. In contrast, biologics may provide longer-lasting protection, albeit with slower onset. Omalizumab is an anti-IgE antibody that sequesters IgE, thereby reducing FcϵRI expression on mast cells and basophils. As a monotherapy, it can increase the clinical threshold dose of food allergen, and when used as an adjunct for food immunotherapy, it decreases severe reactions during buildup phase. Finally, lirentelimab, an anti-Siglec-8 antibody currently in clinical trials, can prevent IgE-mediated anaphylaxis in mice through mast cell inhibition. This review discusses these and other emerging therapies as potential strategies for preventing food-induced anaphylaxis. In contrast to other food allergy treatments which largely focus on individual allergens, blockade of the FcϵRI pathway has the advantage of preventing clinical reactivity from any food.
Role of Neutrophils in Systemic Vasculitides
Authors: Michailidou Despina , Mustelin Tomas , Lood Christian
Published: January 2021

Neutrophils and neutrophil extracellular traps (NETs) contribute to the pathogenesis of many autoimmune diseases, including vasculitis. Though neutrophils, and NETs, can break self-tolerance by being a source of autoantigens for autoantibodies in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, playing a key role in driving the autoimmune response, the role of neutrophils and NETs in large vessel vasculitis, including giant cell arteritis (GCA), is not well understood. In this review, we summarize the current insight into molecular mechanisms contributing to neutrophil-mediated pathology in small and medium vessel vasculitis, as well as provide potential translational perspectives on how neutrophils, and NETs, may partake in large vessel vasculitis, a rare disease entity of unclear pathogenesis.
Substantial Gaps in the Current Fisheries Data Landscape
Authors: Blasco Gordon D. , Ferraro Danielle M. , Cottrell Richard S. , Halpern Benjamin S. , Froehlich Halley E.
Published: January 2021

Effective management of aquatic resources, wild and farmed, has implications for the livelihoods of dependent communities, food security, and ecosystem health. Good management requires information on the status of harvested species, yet many gaps remain in our understanding of these species and systems, in particular the lack of taxonomic resolution of harvested species. To assess these gaps we compared the occurrence of landed species (freshwater and marine) from the United Nations Food and Agriculture Organization (FAO) global fisheries production database to those in the International Union for Conservation of Nature (IUCN) Red List and the RAM Legacy Stock Assessment Database, some of the largest and most comprehensive global datasets of consumed aquatic species. We also quantified the level of resolution and trends in taxonomic reporting for all landed taxa in the FAO database. Of the 1,695 consumed aquatic species or groups in the FAO database considered in this analysis, a large portion (35%) are missing from both of the other two global datasets, either IUCN or RAM, used to monitor, manage, and protect aquatic resources. Only a small number of all fished taxa reported in FAO data (150 out of 1,695; 9%) have both a stock assessment in RAM and a conservation assessment in IUCN. Furthermore, 40% of wild caught landings are not reported to the species level, limiting our ability to effectively account for the environmental impacts of wild harvest. Landings of invertebrates (44%) and landings in Asia (>75%) accounted for the majority of harvest without species specific information in 2018. Assessing the overlap of species which are both farmed and fished to broadly map possible interactions – which can help or hinder wild populations - we found 296 species, accounting for 12% of total wild landings globally, and 103 countries and territories that have overlap in the species caught in the wild and produced through aquaculture. In all, our work highlights that while fisheries management is improving in many areas there remain key gaps in data resolution that are critical for fisheries assessments and conservation of aquatic systems into the future.
Chlamydia trachomatis Plasmid Protein pORF5 Up-Regulates ZFAS1 to Promote Host Cell Survival via MAPK/p38 Pathway
Authors: Wen Yating , Chen Hongliang , Luo Fangzhen , Zhao Lanhua , Shu Mingyi , Su Shengmei , Zhao Yuqi , Huang Qiulin , Li Zhongyu
Published: January 2021

Long non-coding RNAs (lncRNAs) have been demonstrated to play essential roles in many diseases. However, few studies have shown that lncRNAs take part in the pathogenesis of Chlamydia trachomatis (C. trachomatis). Here, we used a lncRNA microarray to detect the global lncRNA expression profiles in HeLa cells transfected with pORF5 plasmid protein, an important virulence factor for C. trachomatis. The differentially expressed lncRNAs and mRNAs screened by microarray were selected for validation by quantitative real-time PCR. The up-regulated lncRNA zinc finger antisense 1 (ZFAS1) was presumed to involved in MAPK pathways by bioinformatics analysis. Inhibition of ZFAS1 decreased the apoptotic rate of pORF5 and reduced the infectivity of C. trachomatis, and MAPK/p38 pathway was involved in anti-apoptotic effect induced by ZFAS1. Therefore, the present study confirmed that pORF5 up-regulates ZFAS1 to promote host cell survival via MAPK/p38 pathway and influences the infectivity of C. trachomatis.
Immunomodulatory Properties of a γ-Aminobutyric Acid-Enriched Strawberry Juice Produced by Levilactobacillus brevis CRL 2013
Authors: Cataldo Pablo G. , Villena Julio , Elean Mariano , Savoy de Giori Graciela , Saavedra Lucila , Hebert Elvira M.
Published: January 2021

Gamma-aminobutyric acid (GABA) plays a key role in mammals as the major inhibitory neurotransmitter of the central nervous system. Although GABA may not be able to cross the human blood-brain barrier, it was approved as a food ingredient because of its benefits to the host after oral administration including anti-hypertensive, anti-depressant and anti-inflammatory activities. Considering the current trend toward the development of new functional and natural products and that microbial fermentation is one of the most promising methods to produce this non-protein amino acid, the in situ production of GABA through fermentation of strawberry and blueberry juices by the efficient GABA producer strain, Levilactobacillus brevis (formerly known as Lactobacillus brevis) CRL 2013, was evaluated. A high GABA production (262 mM GABA) was obtained after fermenting strawberry juice supplemented with yeast extract for 168 h, being GABA yield significantly higher in strawberry juices than in the blueberry ones. Thus, GABA-enriched fermented strawberry juice (FSJ) was selected to carry out in vivo and in vitro studies. The in vitro functional analysis of the GABA-enriched FSJ demonstrated its ability to significantly decrease the expression of cox-2 gene in LPS stimulated RAW 264.7 macrophages. In addition, in vivo studies in mice demonstrated that both, L. brevis CRL 2013 and the GABA-enriched FSJ were capable of reducing the levels of peritoneal, intestinal and serum TNF-α, IL-6, and CXCL1, and increasing IL-10 and IFN-γ in mice exposed to an intraperitoneal challenge of LPS. Of note, the GABA-enriched FSJ was more efficient than the CRL 2013 strain to reduce the pro-inflammatory factors and enhance IL-10 production. These results indicated that the CRL 2013 strain exerts anti-inflammatory effects in the context of LPS stimulation and that this effect is potentiated by fermentation. Our results support the potential use of L. brevis CRL 2013 as an immunomodulatory starter culture and strawberry juice as a remarkable vegetable matrix for the manufacture of GABA-enriched fermented functional foods capable of differentially modulating the inflammatory response triggered by TLR4 activation.
Efficient, Rapid, and Sensitive Detection of Plant RNA Viruses With One-Pot RT-RPA–CRISPR/Cas12a Assay
Authors: Aman Rashid , Mahas Ahmed , Marsic Tin , Hassan Norhan , Mahfouz Magdy M.
Published: January 2021

Most viruses that infect plants use RNA to carry their genomic information; timely and robust detection methods are crucial for efficient control of these diverse pathogens. The RNA viruses, potexvirus (Potexvirus, family Alphaflexiviridae), potyvirus (Potyvirus, family Potyviridae), and tobamovirus (Tobamovirus, family Virgaviridae) are among the most economically damaging pathogenic plant viruses, as they are highly infectious and distributed worldwide. Their infection of crop plants, alone or together with other viruses, causes severe yield losses. Isothermal nucleic acid amplification methods, such as loop-mediated isothermal amplification (LAMP), recombinase polymerase amplification (RPA), and others have been harnessed for the detection of DNA- and RNA-based viruses. However, they have a high rate of non-specific amplification and other drawbacks. The collateral activities of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated nuclease Cas systems such as Cas12 and Cas14 (which act on ssDNA) and Cas13 (which acts on ssRNA) have recently been exploited to develop highly sensitive, specific, and rapid detection platforms. Here, we report the development of a simple, rapid, and efficient RT- RPA method, coupled with a CRISPR/Cas12a-based one-step detection assay, to detect plant RNA viruses. This diagnostic method can be performed at a single temperature in less than 30 min and integrated with an inexpensive commercially available fluorescence visualizer to facilitate rapid, in-field diagnosis of plant RNA viruses. Our developed assay provides an efficient and robust detection platform to accelerate plant pathogen detection and fast-track containment strategies.
Prevention and Alleviation of Dextran Sulfate Sodium Salt-Induced Inflammatory Bowel Disease in Mice With Bacillus subtilis-Fermented Milk via Inhibition of the Inflammatory Responses and Regulation of the Intestinal Flora
Authors: Zhang Xuan , Tong Yanjun , Lyu Xiaomei , Wang Jing , Wang Yuxue , Yang Ruijin
Published: January 2021

The pathogenesis of inflammatory bowel disease (IBD) might be related to the local inflammatory damage and the dysbacteriosis of intestinal flora. Probiotics can regulate the intestinal flora and ameliorate IBD. The probiotic Bacillus subtilis strain B. subtilis JNFE0126 was used as the starter of fermented milk. However, the therapeutic effects of B. subtilis-fermented milk on IBD remain to be explored. In this research, the therapeutic effect of B. subtilis-fermented milk on dextran sulfate sodium salt (DSS)-induced IBD mouse model was evaluated. Besides, the expression of pro-inflammatory/anti-inflammatory cytokines, the proliferation of the intestinal stem cells, and the reconstruction of the mucosa barrier were investigated. Finally, alteration of the gut microbiota was investigated by taxonomic analysis. As shown by the results, the disease activity index (DAI) of IBD was significantly decreased through oral administration of B. subtilis (JNFE0126)-fermented milk, and intestinal mucosa injury was attenuated. Moreover, B. subtilis could reduce the inflammatory response of the intestinal mucosa, induce proliferation of the intestinal stem cell, and promote reconstruction of the mucosal barrier. Furthermore, B. subtilis could rebalance the intestinal flora, increasing the abundance of Bacillus, Alistipes, and Lactobacillus while decreasing the abundance of Escherichia and Bacteroides. In conclusion, oral administration of the B. subtilis-fermented milk could alleviate DSS-induced IBD via inhibition of inflammatory response, promotion of the mucosal barrier reconstruction, and regulation of the intestinal flora.
A Fully-Immersive and Automated Virtual Reality System to Assess the Six Domains of Cognition: Protocol for a Feasibility Study
Authors: Lim Jie En , Wong Wei Teen , Teh Tuan Ann , Lim Soon Huat , Allen John Carson , Quah Joanne Hui Min , Malhotra Rahul , Tan Ngiap Chuan
Published: January 2021

Introduction: Dementia is increasing in prevalence in aging populations. Current questionnaire-based cognitive assessments may not comprehensively assess cognitive function and real-time task-performance. Virtual reality (VR) technology has been used in cognitive assessments but existing systems have limited scope in evaluating all cognitive domains. We have developed a novel, fully-immersive VR system (CAVIRE: Cognitive Assessment by VIrtual REality), which incorporates automated audio-visual instructions. An automated scoring matrix to assess the six cognitive domains—perceptual-motor function, executive function, complex attention, social cognition, learning and memory, and language—is embedded in the CAVIRE system.

Aims: The primary aim is to evaluate the feasibility of using the CAVIRE system to assess cognitive function of participants across different age groups from 35 to 84 years old. The secondary aims are to determine the CAVIRE performance-indices (completion time and scores) of the participants and to assess their acceptability toward the use of CAVIRE as a modality for cognitive assessment.

Methods: One hundred and seventy-five participants will be assessed by CAVIRE at a primary care clinic in Singapore. They will be first assessed using questionnaires: Montreal Cognitive Assessment (MoCA), Abbreviated Mental Test (AMT), Mini-Mental State Examination (MMSE), Basic Activities of Daily Living (BADLs), Instrumental Activities of Daily Living (IADLs). Those aged 65–84 years will be grouped into cognitively intact (n = 50, MoCA score ≥ 26) and cognitively impaired (n = 50, MoCA < 26). The CAVIRE performance-indices of cognitively healthy younger participants aged 35–64 years (n = 75) will serve as benchmark references. CAVIRE auto-computes the participant's performance-indices in 13 different segments. The tasks include domestic chores, memory, shopping, and social interactions. The proportion of participants who complete the entire VR assessment in each age group will be evaluated as feasibility indicators. The CAVIRE performance-indices will be compared across the different age groups. Feedback on the acceptability of the CAVIRE system will be collated and compared among the participants across the age groups.

Significance: CAVIRE is designed to assess the six domains of cognitive function using VR. The results of this feasibility study will provide insights for the implementation of the CAVIRE system as an alternative modality of cognitive assessment in the community.
Sensor-Based Control for Collaborative Robots: Fundamentals, Challenges, and Opportunities
Authors: Cherubini Andrea , Navarro-Alarcon David
Published: January 2021

The objective of this paper is to present a systematic review of existing sensor-based control methodologies for applications that involve direct interaction between humans and robots, in the form of either physical collaboration or safe coexistence. To this end, we first introduce the basic formulation of the sensor-servo problem, and then, present its most common approaches: vision-based, touch-based, audio-based, and distance-based control. Afterwards, we discuss and formalize the methods that integrate heterogeneous sensors at the control level. The surveyed body of literature is classified according to various factors such as: sensor type, sensor integration method, and application domain. Finally, we discuss open problems, potential applications, and future research directions.
Evaluation of Risk Behavior in Gambling Addicted and Opioid Addicted Individuals
Authors: Gorzelańczyk Edward J. , Walecki Piotr , Błaszczyszyn Monika , Laskowska Ewa , Kawala-Sterniuk Aleksandra
Published: January 2021

Evidence suggests that both opioid addicted and gambling addicted individuals are characterized by higher levels of risky behavior in comparison to healthy people. It has been shown that the administration of substitution drugs can reduce cravings for opioids and the risky decisions made by individuals addicted to opioids. Although it is suggested that the neurobiological foundations of addiction are similar, it is possible that risk behaviors in opioid addicts may differ in detail from those addicted to gambling. The aim of this work was to compare the level of risk behavior in individuals addicted to opioid, with that of individuals addicted to gambling, using the Iowa Gambling Task (IGT). The score and response time during the task were measured. It was also observed, in the basis of the whole IGT test, that individuals addicted to gambling make riskier decisions in comparison to healthy individuals from the control group but less riskier decisions in comparison to individuals addicted to opioids, before administration of methadone and without any statistically significant difference after administration of methadone—as there has been growing evidence that methadone administration is strongly associated with a significant decrease in risky behavior.
Caffeine and Parkinson’s Disease: Multiple Benefits and Emerging Mechanisms
Authors: Ren Xiangpeng , Chen Jiang-Fan
Published: January 2021

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, characterized by dopaminergic neurodegeneration, motor impairment and non-motor symptoms. Epidemiological and experimental investigations into potential risk factors have firmly established that dietary factor caffeine, the most-widely consumed psychoactive substance, may exerts not only neuroprotective but a motor and non-motor (cognitive) benefits in PD. These multi-benefits of caffeine in PD are supported by convergence of epidemiological and animal evidence. At least six large prospective epidemiological studies have firmly established a relationship between increased caffeine consumption and decreased risk of developing PD. In addition, animal studies have also demonstrated that caffeine confers neuroprotection against dopaminergic neurodegeneration using PD models of mitochondrial toxins (MPTP, 6-OHDA, and rotenone) and expression of α-synuclein (α-Syn). While caffeine has complex pharmacological profiles, studies with genetic knockout mice have clearly revealed that caffeine’s action is largely mediated by the brain adenosine A2Areceptor (A2AR) and confer neuroprotection by modulating neuroinflammation and excitotoxicity and mitochondrial function. Interestingly, recent studies have highlighted emerging new mechanisms including caffeine modulation of α-Syn degradation with enhanced autophagy and caffeine modulation of gut microbiota and gut-brain axis in PD models. Importantly, since the first clinical trial in 2003, United States FDA has finally approved clinical use of the A2AR antagonist istradefylline for the treatment of PD with OFF-time in Sept. 2019. To realize therapeutic potential of caffeine in PD, genetic study of caffeine and risk genes in human population may identify useful pharmacogenetic markers for predicting individual responses to caffeine in PD clinical trials and thus offer a unique opportunity for “personalized medicine” in PD.
Beyond Technologies of Electroencephalography-Based Brain-Computer Interfaces: A Systematic Review From Commercial and Ethical Aspects
Authors: Fontanillo Lopez Cesar Augusto , Li Guangye , Zhang Dingguo
Published: January 2021

The deployment of electroencephalographic techniques for commercial applications has undergone a rapid growth in recent decades. As they continue to expand in the consumer markets as suitable techniques for monitoring the brain activity, their transformative potential necessitates equally significant ethical inquiries. One of the main questions, which arises then when evaluating these kinds of applications, is whether they should be aligned or not with the main ethical concerns reported by scholars and experts. Thus, the present work attempts to unify these disciplines of knowledge by performing a comprehensive scan of the major electroencephalographic market applications as well as their most relevant ethical concerns arising from the existing literature. In this literature review, different databases were consulted, which presented conceptual and empirical discussions and findings about commercial and ethical aspects of electroencephalography. Subsequently, the content was extracted from the articles and the main conclusions were presented. Finally, an external assessment of the outcomes was conducted in consultation with an expert panel in some of the topic areas such as biomedical engineering, biomechatronics, and neuroscience. The ultimate purpose of this review is to provide a genuine insight into the cutting-edge practical attempts at electroencephalography. By the same token, it seeks to highlight the overlap between the market needs and the ethical standards that should govern the deployment of electroencephalographic consumer-grade solutions, providing a practical approach that overcomes the engineering myopia of certain ethical discussions.
Recording of Electrically Evoked Neural Activity and Bladder Pressure Responses in Awake Rats Chronically Implanted With a Pelvic Nerve Array
Authors: Payne Sophie C. , Wiedmann Nicole M. , Eiber Calvin D. , Wong Agnes W. , Senn Philipp , Osborne Peregrine B. , Keast Janet R. , Fallon James B.
Published: January 2021

Bioelectronic medical devices are well established and widely used in the treatment of urological dysfunction. Approved targets include the sacral S3 spinal root and posterior tibial nerve, but an alternate target is the group of pelvic splanchnic nerves, as these contain sacral visceral sensory and autonomic motor pathways that coordinate storage and voiding functions of the bladder. Here, we developed a device suitable for long-term use in an awake rat model to study electrical neuromodulation of the pelvic nerve (homolog of the human pelvic splanchnic nerves). In male Sprague-Dawley rats, custom planar four-electrode arrays were implanted over the distal end of the pelvic nerve, close to the major pelvic ganglion. Electrically evoked compound action potentials (ECAPs) were reliably detected under anesthesia and in chronically implanted, awake rats up to 8 weeks post-surgery. ECAP waveforms showed three peaks, with latencies that suggested electrical stimulation activated several subpopulations of myelinated A-fiber and unmyelinated C-fiber axons. Chronic implantation of the array did not impact on voiding evoked in awake rats by continuous cystometry, where void parameters were comparable to those published in naïve rats. Electrical stimulation with chronically implanted arrays also induced two classes of bladder pressure responses detected by continuous flow cystometry in awake rats: voiding contractions and non-voiding contractions. No evidence of tissue pathology produced by chronically implanted arrays was detected by immunohistochemical visualization of markers for neuronal injury or noxious spinal cord activation. These results demonstrate a rat pelvic nerve electrode array that can be used for preclinical development of closed loop neuromodulation devices targeting the pelvic nerve as a therapy for neuro-urological dysfunction.