bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Allosteric Mechanism of Src Homology-2 Domain-Containing Protein Tyrosine Phosphatase 2 (SHP2) by Molecular Dynamics Simulations
Authors: Wang Quan , Zhao Wen-Cheng , Fu Xue-Qi , Zheng Qing-Chuan
Published: November 2020

The Src homology-2 (SH2) domain-containing protein tyrosine phosphatase 2 (SHP2, encoded by PTPN11) is a critical allosteric phosphatase for many signaling pathways. Programmed cell death 1 (PD-1) could be phosphorylated at its immunoreceptor tyrosine-based inhibitory motif (ITIM) and immunoreceptor tyrosine-based switch motif (ITSM) and can bind to SHP2 to initiate T cell inactivation. Although the interaction of SHP2-PD-1 plays an important role in the immune process, the complex structure and the allosteric regulation mechanism remain unknown. In this study, molecular dynamics (MD) simulations were performed to study the binding details of SHP2 and PD-1, and explore the allosteric regulation mechanism of SHP2. The results show that ITIM has a preference to bind to the N-SH2 domain and ITSM has almost the same binding affinity to the N-SH2 and C-SH2 domain. Only when ITIM binds to the N-SH2 domain and ITSM binds to the C-SH2 domain can the full activation of SHP2 be obtained. The binding of ITIM and ITSM could change the motion mode of SHP2 and switch it to the activated state.
Poly (Glycerol Sebacate)-Based Bio-Artificial Multiporous Matrix for Bone Regeneration
Authors: Liang Bo , Shi Qiang , Xu Jia , Chai Yi-Min , Xu Jian-Guang
Published: November 2020

In recent years, bone repair biomaterials that combine cells and bioactive factors are superior to autologous and allogeneic bone implants. However, neither natural nor synthetic biomaterials can possess all desired qualities such as strength, porosity, and biological activity. In this study, we used poly (glycerol sebacate) (PGS), a synthetic material with great osteogenic potential that has attracted more attention in the field of tissue (such as bone tissue) regeneration owing to its good biocompatibility and high elasticity. It also has the advantage of being regulated by material synthesis to match the bone tissue's strength and can be easily modified to become functional. However, pure PGS lacks functional groups and hydrophilicity. Therefore, we used PGS as the substrate to graft the adhesive ligands RGD and vascular endothelial growth factor mimetic peptide. The bone repair scaffold can be prepared through photo crosslinking, as it not only improves hydrophobicity but also promotes vascularization and accelerates osteogenesis. Simultaneously, we improved the preparation method of hydrogels after freeze-drying and crosslinking to form a sponge-like structure and to easily regenerate blood vessels. In summary, a bone repair scaffold was prepared to meet the structural and biological requirements. It proved to serve as a potential bone-mimicking scaffold by enhancing tissue regenerative processes such as cell infiltration and vascularization and subsequent replacement by the native bone tissue.
The Use of Adjunctive Steroids in Central Nervous Infections
Authors: Gundamraj Shalini , Hasbun Rodrigo
Published: November 2020

Central nervous system (CNS) infections continue to be associated with significant neurological morbidity and mortality despite various existing therapies. Adjunctive steroid therapy has been employed clinically to reduce inflammation in the treatment of CNS infections across various causative pathogens. Steroid therapy can potentially improve clinical outcomes including reducing mortality rates, provide no significant benefit, or cause worsened outcomes, based on the causative agent of infection. The data on benefits or harms of adjunctive steroid therapy is not consistent in outcome or density through CNS infections, and varies based on the disease diagnosis and pathogen. We summarize the existing literature on the effects of adjunctive steroid therapy on outcome for a number of CNS infections, including bacterial meningitis, herpes simplex virus, West Nile virus, tuberculosis meningitis, cryptococcal meningitis, Angiostrongylus cantonensis, neurocysticercosis, autoimmune encephalitis, toxoplasmosis, and bacterial brain abscess. We describe that while steroid therapy is beneficial and supported in pathogens such as pneumococcal meningitis and tuberculosis, for other diseases, like Listeria monocytogenes and Cryptococcus neoformans they are associated with worse outcomes. We highlight areas of consistent and proven findings and those which need more evidence for supported beneficial clinical use of adjunctive steroid therapy.
Compositional Shift of Oral Microbiota Following Surgical Resection of Tongue Cancer
Authors: Kageyama Shinya , Nagao Yuka , Ma Jiale , Asakawa Mikari , Yoshida Ryoji , Takeshita Toru , Hirosue Akiyuki , Yamashita Yoshihisa , Nakayama Hideki
Published: November 2020

Salivary microbiota is considered a source of microorganisms for the respiratory and digestive tracts, and a trigger for diseases in these distant organs. Meanwhile, the microbiota on the tongue surface is thought to be a major source of salivary microbiota. Therefore, surgical resection of the tongue for definitive treatment of oral cancer could drastically change the salivary bacterial balance and virulence. Here, we investigated the shift of the salivary microbiota following surgical resection in patients with tongue cancer. The stimulated saliva samples were collected from 25 tongue cancer patients pre- and post-resection of the tongue, and bacterial density and composition was determined using quantitative PCR analysis and 16S ribosomal RNA (rRNA) gene sequencing, respectively. Although no significant difference in the total bacterial density in saliva pre- and post-surgery was observed, the bacterial composition significantly differed according to the analysis of similarity. Among predominant operational taxonomic units (OTUs) with ≥1% of relative abundance, the proportions of OTUs corresponding to Streptococcus salivarius, Prevotellamelaninogenica, and Prevotellahisticola were significantly decreased following the tongue resection. On the other hand, the proportions of OTUs corresponding to Lautropiamirabilis, Neisseriaflava, Streptococcussanguinis, and Fusobacterium nucleatum, known to be inhabitants of dental plaque, were significantly increased. These results suggest that surgical resection of the tongue causes a compositional shift of the salivary microbiota, characterized by an increase in bacterial species derived from dental plaque, including periodontal pathogens. These results suggest the necessity of more careful and frequent postoperative oral care after surgical resection of tongue cancer.
Biomarkers for Heart Failure Prognosis: Proteins, Genetic Scores and Non-coding RNAs
Authors: Shrivastava Apurva , Haase Tina , Zeller Tanja , Schulte Christian
Published: November 2020

Heart failure (HF) is a complex disease in which cardiomyocyte injury leads to a cascade of inflammatory and fibrosis pathway activation, thereby causing decrease in cardiac function. As a result, several biomolecules are released which can be identified easily in circulating body fluids. The complex biological processes involved in the development and worsening of HF require an early treatment strategy to stop deterioration of cardiac function. Circulating biomarkers provide not only an ideal platform to detect subclinical changes, their clinical application also offers the opportunity to monitor disease treatment. Many of these biomarkers can be quantified with high sensitivity; allowing their clinical application to be evaluated beyond diagnostic purposes as potential tools for HF prognosis. Though the field of biomarkers is dominated by protein molecules, non-coding RNAs (microRNAs, long non-coding RNAs, and circular RNAs) are novel and promising biomarker candidates that encompass several ideal characteristics required in the biomarker field. The application of genetic biomarkers as genetic risk scores in disease prognosis, albeit in its infancy, holds promise to improve disease risk estimation. Despite the multitude of biomarkers that have been available and identified, the majority of novel biomarker candidates are not cardiac-specific, and instead may simply be a readout of systemic inflammation or other pathological processes. Thus, the true value of novel biomarker candidates in HF prognostication remains unclear. In this article, we discuss the current state of application of protein, genetic as well as non-coding RNA biomarkers in HF risk prognosis.
Interdisciplinary Research in Artificial Intelligence: Challenges and Opportunities
Authors: Kusters Remy , Misevic Dusan , Berry Hugues , Cully Antoine , Le Cunff Yann , Dandoy Loic , Díaz-Rodríguez Natalia , Ficher Marion , Grizou Jonathan , Othmani Alice , Palpanas Themis , Komorowski Matthieu , Loiseau Patrick , Moulin Frier Clément , Nanini Santino , Quercia Daniele , Sebag Michele , Soulié Fogelman Françoise , Taleb Sofiane , Tupikina Liubov , Sahu Vaibhav , Vie Jill-Jênn , Wehbi Fatima
Published: November 2020

The use of artificial intelligence (AI) in a variety of research fields is speeding up multiple digital revolutions, from shifting paradigms in healthcare, precision medicine and wearable sensing, to public services and education offered to the masses around the world, to future cities made optimally efficient by autonomous driving. When a revolution happens, the consequences are not obvious straight away, and to date, there is no uniformly adapted framework to guide AI research to ensure a sustainable societal transition. To answer this need, here we analyze three key challenges to interdisciplinary AI research, and deliver three broad conclusions: 1) future development of AI should not only impact other scientific domains but should also take inspiration and benefit from other fields of science, 2) AI research must be accompanied by decision explainability, dataset bias transparency as well as development of evaluation methodologies and creation of regulatory agencies to ensure responsibility, and 3) AI education should receive more attention, efforts and innovation from the educational and scientific communities. Our analysis is of interest not only to AI practitioners but also to other researchers and the general public as it offers ways to guide the emerging collaborations and interactions toward the most fruitful outcomes.
The Molecular Mechanisms Underlying Mitochondria-Associated Endoplasmic Reticulum Membrane-Induced Insulin Resistance
Authors: Cheng Han , Gang Xiaokun , He Guangyu , Liu Yujia , Wang Yingxuan , Zhao Xue , Wang Guixia
Published: November 2020

Mitochondria and the endoplasmic reticulum (ER) are connected at multiple sitesviawhat are known as mitochondria-associated ER membranes (MAMs). These associations are known to play an important role in maintaining cellular homeostasis. Impaired MAM signaling has wide-ranging effects in many diseases, such as obesity, diabetes, and neurodegenerative disorders. Accumulating evidence has suggested that MAMs influence insulin signaling through different pathways, including those associated with Ca2+signaling, lipid metabolism, mitochondrial function, ER stress responses, and inflammation. Altered MAM signaling is a common feature of insulin resistance in different tissues, including the liver, muscle, and even the brain. In the liver, MAMs are key glucose-sensing regulators and have been proposed to be a hub for insulin signaling. Impaired MAM integrity has been reported to disrupt hepatic responses to changes in glucose availability during nutritional transition and to induce hepatic insulin resistance. Meanwhile, these effects can be rescued by the reinforcement of MAM interactions. In contrast, several studies have proposed that enhanced ER-mitochondria connections are detrimental to hepatic insulin signaling and can lead to mitochondrial dysfunction. Thus, given these contradictory results, the role played by the MAM in the regulation of hepatic insulin signaling remains elusive. Similarly, in skeletal muscle, enhanced MAM formation may be beneficial in the early stage of diabetes, whereas continuous MAM enhancement aggravates insulin resistance. Furthermore, recent studies have suggested that ER stress may be the primary pathway through which MAMs induce brain insulin resistance, especially in the hypothalamus. This review will discuss the possible mechanisms underlying MAM-associated insulin resistance as well as the therapeutic potential of targeting the MAM in the treatment of type 2 diabetes.
Multi-Approach Bioinformatics Analysis of Curated Omics Data Provides a Gene Expression Panorama for Multiple Cancer Types
Authors: Feltes Bruno César , Poloni Joice de Faria , Nunes Itamar José Guimarães , Faria Sara Socorro , Dorn Marcio
Published: November 2020

Studies describing the expression patterns and biomarkers for the tumoral process increase in number every year. The availability of new datasets, although essential, also creates a confusing landscape where common or critical mechanisms are obscured amidst the divergent and heterogeneous nature of such results. In this work, we manually curated the Gene Expression Omnibus using rigorous filtering criteria to select the most homogeneous and highest quality microarray and RNA-seq datasets from multiple types of cancer. By applying systems biology approaches, combined with machine learning analysis, we investigated possible frequently deregulated molecular mechanisms underlying the tumoral process. Our multi-approach analysis of 99 curated datasets, composed of 5,406 samples, revealed 47 differentially expressed genes in all analyzed cancer types, which were all in agreement with the validation using TCGA data. Results suggest that the tumoral process is more related to the overexpression of core deregulated machinery than the underexpression of a given gene set. Additionally, we identified gene expression similarities between different cancer types not described before and performed an overall survival analysis using 20 cancer types. Finally, we were able to suggest a core regulatory mechanism that could be frequently deregulated.
The Neoantigen Landscape of Mycosis Fungoides
Authors: Sivanand Arunima , Hennessey Dylan , Iyer Aishwarya , O’Keefe Sandra , Surmanowicz Philip , Vaid Gauravi , Xiao Zixuan , Gniadecki Robert
Published: November 2020

Background

Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma, for which there is no cure. Immune checkpoint inhibitors have been tried in MF but the results have been inconsistent. To gain insight into the immunogenicity of MF we characterized the neoantigen landscape of this lymphoma, focusing on the known predictors of responses to immunotherapy: the quantity, HLA-binding strength and subclonality of neoantigens.

Methods

Whole exome and whole transcriptome sequences were obtained from 24 MF samples (16 plaques, 8 tumors) from 13 patients. Bioinformatic pipelines (Mutect2, OptiType, MuPeXi) were used for mutation calling, HLA typing, and neoantigen prediction. PhyloWGS was used to subdivide malignant cells into stem and clades, to which neoantigens were matched to determine their clonality.

Results

MF has a high mutational load (median 3,217 non synonymous mutations), resulting in a significant number of total neoantigens (median 1,309 per sample) and high-affinity neoantigens (median 328). In stage I disease most neoantigens were clonal but with stage progression, 75% of lesions had >50% subclonal antigens and 53% lesions had CSiN scores <1. There was very little overlap in neoantigens across patients or between different lesions on the same patient, indicating a high degree of heterogeneity.

Conclusions

The neoantigen landscape of MF is characterized by high neoantigen load and significant subclonality which could indicate potential challenges for immunotherapy in patients with advanced-stage disease.
Precision Nutrition in Chronic Inflammation
Authors: Demetrowitsch Tobias J. , Schlicht Kristina , Knappe Carina , Zimmermann Johannes , Jensen-Kroll Julia , Pisarevskaja Alina , Brix Fynn , Brandes Juliane , Geisler Corinna , Marinos Georgios , Sommer Felix , Schulte Dominik M. , Kaleta Christoph , Andersen Vibeke , Laudes Matthias , Schwarz Karin , Waschina Silvio
Published: November 2020

The molecular foundation of chronic inflammatory diseases (CIDs) can differ markedly between individuals. As our understanding of the biochemical mechanisms underlying individual disease manifestations and progressions expands, new strategies to adjust treatments to the patient’s characteristics will continue to profoundly transform clinical practice. Nutrition has long been recognized as an important determinant of inflammatory disease phenotypes and treatment response. Yet empirical work demonstrating the therapeutic effectiveness of patient-tailored nutrition remains scarce. This is mainly due to the challenges presented by long-term effects of nutrition, variations in inter-individual gastrointestinal microbiota, the multiplicity of human metabolic pathways potentially affected by food ingredients, nutrition behavior, and the complexity of food composition. Historically, these challenges have been addressed in both human studies and experimental model laboratory studies primarily by using individual nutrition data collection in tandem with large-scale biomolecular data acquisition (e.g. genomics, metabolomics, etc.). This review highlights recent findings in the field of precision nutrition and their potential implications for the development of personalized treatment strategies for CIDs. It emphasizes the importance of computational approaches to integrate nutritional information into multi-omics data analysis and to predict which molecular mechanisms may explain how nutrients intersect with disease pathways. We conclude that recent findings point towards the unexhausted potential of nutrition as part of personalized medicine in chronic inflammation.
Modeling the Dynamics of Multispecies Fisheries: A Case Study in the Coastal Water of North Yellow Sea, China
Authors: Wo Jia , Zhang Chongliang , Pan Xindong , Xu Binduo , Xue Ying , Ren Yiping
Published: November 2020

Ecosystem models have been developed for detecting community responses to fishing pressure and have been widely applied to predict the ecological effects of fisheries management. Key challenges of ecosystem modeling lie in the insufficient quantity and quality of data, which is unfortunately common in the marine ecosystems of many developing countries. In this study, we aim to model the dynamics of multispecies fisheries under data-limited circumstances, using a multispecies size-spectrum model (MSSM) implemented in the coastal ecosystem of North Yellow Sea, China. To make most of available data, we incorporated a range of data-limited methods for estimating the life-history parameters and conducted model validation according to empirical data. Additionally, sensitivity analyses were conducted to evaluate the impacts of input parameters on model predictions regarding the uncertainty of data and estimating methods. Our results showed that MSSM could provide reasonable predictions of community size spectra and appropriately reflect the community composition in the studied area, whereas the predictions of fisheries yields were biased for certain species. Errors in recruitment parameters were most influential on the prediction of species abundance, and errors in fishing efforts substantially affected community-level indicators. This study built a framework to integrate parameter estimation, model validation, and sensitivity analyses altogether, which could guide model development in similar mixed and data-limited fisheries and promote the use of size-spectrum model for ecosystem-based fisheries management.
Intensive Care Unit-Acquired Weakness: A Review of Recent Progress With a Look Toward the Future
Authors: Wang Wenkang , Xu Chuanjie , Ma Xinglong , Zhang Xiaoming , Xie Peng
Published: November 2020

Intensive care unit-acquired weakness (ICU-AW), a common neuromuscular complication associated with patients in the ICU, is a type of skeletal muscle dysfunction that commonly occurs following sepsis, mobility restriction, hyperglycemia, and the use of glucocorticoids or neuromuscular blocking agents. ICU-AW can lead to delayed withdrawal of mechanical ventilation and extended hospitalization. Patients often have poor prognosis, limited mobility, and severely affected quality of life. Currently, its pathogenesis is uncertain, with unavailability of specific drugs or targeted therapies. ICU-AW has gained attention in recent years. This manuscript reviews the current research status of the epidemiology, pathogenesis, diagnosis, and treatment methods for ICU-AW and speculates the novel perspectives for future research.
Osteoporosis in Rheumatoid Arthritis: Dangerous Liaisons
Authors: Llorente Irene , García-Castañeda Noelia , Valero Cristina , González-Álvaro Isidoro , Castañeda Santos
Published: November 2020

Osteoporosis has been classically considered a comorbidity of rheumatoid arthritis (RA). However, recent advances in the pathogenesis of osteoporosis in RA have shown a close interplay between cells of the immune system and those involved in bone remodeling, introducing new actors into the classic route in which osteoclast activation is related to the RANK/RANKL/OPG pathway. In fact, the inflammatory state in early stages of RA, mediated by interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor (TNF)-α has the ability to activate and differentiate osteoclasts not only through their relationship with RANKL, but also through the Wnt/DKK1/sclerostin pathway, leading to bone loss. The role of synovial fibroblasts and activated T lymphocytes in the expression of the RANKL system and its connection to bone destruction is also depicted. In addition, autoantibodies such as rheumatoid factor and anti-citrullinated protein antibodies are other pathogenic mechanisms for the development of bone erosions and systemic osteoporosis in RA, even before the onset of arthritis. The aim of this review is to unravel the relationship between different factors involved in the development of osteoporosis in RA patients, both the classic factors and the most novel, based on the relationship of autoantibodies with bone remodeling. Furthermore, we propose that bone mineral density measured by different techniques may be helpful as a biomarker of severity in early arthritis patients.
Glycogen Phosphorylase: A Drug Target of Amino Alcohols in Echinococcus granulosus, Predicted by a Computer-Aided Method
Authors: Liu Congshan , Yin Jianhai , Hu Wei , Zhang Haobing
Published: November 2020

Echinococcosis is an important parasitic disease that threats human health and animal husbandry worldwide. However, the low cure rate of clinical drugs for this disease is a challenge. Hence, novel compounds and specific drug targets are urgently needed. In this study, we identified drug targets of amino alcohols with effects on Echinococcus species. The drug targets were predicted with the idTarget web server. Corresponding three-dimensional structures of the drug targets were built after sequence BLAST analysis and homology modeling. After further screening by molecular docking, the activities of the candidate targets were validated in vitro. We ultimately identified glycogen phosphorylase as a potential drug target for amino alcohols. There are two genes coding glycogen phosphorylase in Echinococcus granulosus (EgGp1 and EgGp2). EgGp1 was abundant in E. granulosus PSCs, while EgGp2 was abundant in the cysts. These proteins were located at suckers and somas of E. granulosus PSCs and near the rostellum of cysts developed from PSCs. The effective compounds docked into a pocket consisting of E124, K543 and K654 and affected (either inhibited or enhanced) the activity of E. granulosus glycogen phosphorylase. In this study, we designed a method to predict drug targets for echinococcosis treatment based on inverse docking. The candidate targets found by this method can contribute not only to understanding of the modes of action of amino alcohols but also to modeling-aided drug design based on targets.
Antagonistic Mechanism of Metabolites Produced by Lactobacillus casei on Lysis of Enterohemorrhagic Escherichia coli
Authors: Aditya Arpita , Peng Mengfei , Young Alana , Biswas Debabrata
Published: November 2020

Enhancing extracellular metabolic byproducts of probiotics is one of the promising strategies to improve overall host health as well as to control enteric infections caused by various foodborne pathogens. However, the underlying mechanism of action of those metabolites and their effective concentrations are yet to be established. In this study, we determined the antibacterial potential of the metabolites in the cell-free culture supernatant (CFCS) collected from wild-typeLactobacillus casei(LCwt) and genetically modified LC to overexpress linoleate isomerase (LCCLA). We also evaluated the mechanism of action of CFCSs collected from the culture of LCwtin the presence or absence of 0.5% peanut flour (CFCSwtand CFCSwt+PF, respectively) and LCCLAalone (CFCSCLA) against enterohemorrhagicEscherichia coli(EHEC). The metabolites present in CFCSwt+PFand CFCSCLAeliminated EHEC within 24 and 48 h, respectively. Whereas CFCSwtfailed to eliminate EHEC but reduced their growth by 6.7 logs (p< 0.05) as compared to the control. Significant downregulation of the expression of cell division gene,ftsZ, supported the observed degree of bactericidal and bacteriostatic properties of the collected CFCSs. Upregulation of EHEC genes related to maintaining cell membrane integrity, DNA damage repair, and molecular chaperons indicated an intensive stress condition imposed by the total metabolites present in CFCSs on EHEC growth and cellular structures. A range of deviated morphological features provoked by the metabolites indicated a membrane-targeted action, in general, to compromise the membrane permeability of EHEC. The information obtained from this study may contribute to a more efficient prevention of EHEC related infections.
Mammalian Cell-Based Immunoassay for Detection of Viable Bacterial Pathogens
Authors: Xu Luping , Bai Xingjian , Tenguria Shivendra , Liu Yi , Drolia Rishi , Bhunia Arun K.
Published: November 2020

Rapid detection of live pathogens is of paramount importance to ensure food safety. At present, nucleic acid-based polymerase chain reaction and antibody-based lateral flow assays are the primary methods of choice for rapid detection, but these are prone to interference from inhibitors, and resident microbes. Moreover, the positive results may neither assure virulence potential nor viability of the analyte. In contrast, the mammalian cell-based assay detects pathogen interaction with the host cells and is responsive to only live pathogens, but the short shelf-life of the mammalian cells is the major impediment for its widespread application. An innovative approach to prolong the shelf-life of mammalian cells by using formalin was undertaken. Formalin (4% formaldehyde)-fixed human ileocecal adenocarcinoma cell line, HCT-8 on 24-well tissue culture plates was used for the capture of viable pathogens while an antibody was used for specific detection. The specificity of the Mammalian Cell-based ImmunoAssay (MaCIA) was validated with Salmonella enterica serovar Enteritidis and Typhimurium as model pathogens and further confirmed against a panel of 15 S. Enteritidis strains, 8 S. Typhimurium, 11 other Salmonella serovars, and 14 non-Salmonella spp. The total detection time (sample-to-result) of MaCIA with artificially inoculated ground chicken, eggs, milk, and cake mix at 1–10 CFU/25 g was 16–21 h using a traditional enrichment set up but the detection time was shortened to 10–12 h using direct on-cell (MaCIA) enrichment. Formalin-fixed stable cell monolayers in MaCIA provide longer shelf-life (at least 14 weeks) for possible point-of-need deployment and multi-sample testing on a single plate.
Plant Genotype Influences Physicochemical Properties of Substrate as Well as Bacterial and Fungal Assemblages in the Rhizosphere of Balsam Poplar
Authors: Rheault Karelle , Lachance Denis , Morency Marie-Josée , Thiffault Évelyne , Guittonny Marie , Isabel Nathalie , Martineau Christine , Séguin Armand
Published: November 2020

Abandoned unrestored mines are an important environmental concern as they typically remain unvegetated for decades, exposing vast amounts of mine waste to erosion. Several factors limit the revegetation of these sites, including extreme abiotic and unfavorable biotic conditions. However, some pioneer tree species having high levels of genetic diversity, such as balsam poplar(Populus balsamifera), can naturally colonize these sites and initiate plant succession. This suggests that some tree genotypes are likely more suited for acclimation to the conditions of mine wastes. In this study, we selected two contrasting mine waste storage facilities (waste rock from a gold mine and tailings from a molybdenum mine) from the Abitibi region of Quebec (Canada), on which poplars were found to have grown naturally. First, we assessedin situthe impact of vegetation presence on each mine waste type. The presence of balsam poplars improved soil health locally by modifying the physicochemical properties (e.g., higher nutrient content and pH) of the mine wastes and causing an important shift in their bacterial and fungal community compositions, going from lithotrophic communities that dominate mine waste environments to heterotrophic communities involved in nutrient cycling. Next, in a greenhouse experiment we assessed the impact of plant genotype when grown in these mine wastes. Ten genotypes ofP. balsamiferawere collected locally, found growing either at the mine sites or in the surrounding natural forest. Tree growth was monitored over two growing seasons, after which the effects of genotype-by-environment interactions were assessed by measuring the physicochemical properties of the substrates and the changes in microbial community assembly. Although substrate type was identified as the main driver of rhizosphere microbiome diversity and community structure, a significant effect due to tree genotype was also detected, particularly for bacterial communities. Plant genotype also influenced aboveground tree growth and the physicochemical properties of the substrates. These results highlight the influence of balsam poplar genotype on the soil environment and the potential importance of tree genotype selection in the context of mine waste revegetation.
Alpha-Synuclein Accumulation and Its Phosphorylation in the Enteric Nervous System of Patients Without Neurodegeneration: An Explorative Study
Authors: Bu Lu-Lu , Huang Kai-Xun , Zheng De-Zhi , Lin Dan-Yu , Chen Ying , Jing Xiu-Na , Liang Yan-Ran , Tao En-Xiang
Published: November 2020

Alpha-synuclein (α-Syn) is widely distributed and involved in the regulation of the nervous system. The phosphorylation of α-Syn at serine 129 (pSer129α-Syn) is known to be closely associated with α-Synucleinopathies, especially Parkinson's disease (PD). The present study aimed to explore the α-Syn accumulation and its phosphorylation in the enteric nervous system (ENS) in patients without neurodegeneration. Patients who underwent colorectal surgery for either malignant or benign tumors that were not suitable for endoscopic resection (n = 19) were recruited to obtain normal intestinal specimens, which were used to assess α-Syn immunoreactivity patterns using α-Syn and pSer129α-Syn antibodies. Furthermore, the sub-location of α-Syn in neurons was identified by α-Syn/neurofilament double staining. Semi-quantitative counting was used to evaluate the expression of α-Syn and pSer129α-Syn in the ENS. Positive staining of α-Syn was detected in all intestinal layers in patients with non-neurodegenerative diseases. There was no significant correlation between the distribution of α-Syn and age (p = 0.554) or tumor stage (p = 0.751). Positive staining for pSer129α-Syn was only observed in the submucosa and myenteric plexus layers. The accumulation of pSer129α-Syn increased with age. In addition, we found that the degenerative changes of the ENS were related to the degree of tumor malignancy (p = 0.022). The deposits of α-Syn were present in the ENS of patients with non-neurodegenerative disorders; particularly the age-dependent expression of pSer129α-Syn in the submucosa and myenteric plexus. The current findings of α-Syn immunostaining in the ENS under near non-pathological conditions weaken the basis of using α-Syn pathology as a suitable hallmark to diagnose α-Synucleinopathies including PD. However, our data provided unique perspectives to study gastrointestinal dysfunction in non-neurodegenerative disorders. These findings provide new evidence to elucidate the neuropathological characteristics and α-Syn pathology pattern of the ENS in non-neurodegenerative conditions.
Acupuncture Improves White Matter Perfusion and Integrity in Rat Model of Vascular Dementia: An MRI-Based Imaging Study
Authors: Ma Si-Ming , Wang Lu , Su Xin-Tong , Yang Na-Na , Huang Jin , Lin Lu-Lu , Shao Jia-Kai , Yang Jing-Wen , Liu Cun-Zhi
Published: November 2020

White matter lesions induced by chronic cerebral hypoperfusion are associated with cognitive impairment in vascular dementia (VaD). Previous studies have shown that acupuncture can ameliorate the cognitive deficits of individuals with VaD. However, the neuroimaging mechanisms of acupuncture on white matter perfusion and integrity remain elusive. In this study, the VaD model was induced by bilateral common carotid arteries occlusion (BCCAO) in rats. Novel object recognition task and Morris water maze were performed to evaluate short-term memory and spatial learning and memory. Arterial spin labeling and diffusion tensor imaging (DTI) were used to measure the cerebral blood flow (CBF) and the white matter integrity. Pathological examinations detected the myelin loss and concomitant neuroinflammation. The results demonstrate that BCCAO rats with reduced CBF exhibited worse performance and altered DTI parameters, including decreased fractional anisotropy, increased radial diffusivity, and axial diffusivity in white matter regions. Acupuncture ameliorated cognitive impairment, increased CBF, and protected the myelin sheath integrity but not the axons of BCCAO rats. These protective effects of acupuncture on white matter were significantly correlated with improved CBF. Pathological examination confirmed that the loss of myelin basic protein and microglial accumulation associated IL-1β and IL-6 production were attenuated by acupuncture treatment. Our findings suggest that acupuncture protects cognitive function of BCCAO rats by improving white matter perfusion and integrity.
Cannabinoids, Inner Ear, Hearing, and Tinnitus: A Neuroimmunological Perspective
Authors: Perin Paola , Mabou Tagne Alex , Enrico Paolo , Marino Franca , Cosentino Marco , Pizzala Roberto , Boselli Cinzia
Published: November 2020

Cannabis has been used for centuries for recreational and therapeutic purposes. Whereas, the recreative uses are based on the psychotropic effect of some of its compounds, its therapeutic effects range over a wide spectrum of actions, most of which target the brain or the immune system. Several studies have found cannabinoid receptors in the auditory system, both at peripheral and central levels, thus raising the interest in cannabinoid signaling in hearing, and especially in tinnitus, which is affected also by anxiety, memory, and attention circuits where cannabinoid effects are well described. Available studies on animal models of tinnitus suggest that cannabinoids are not likely to be helpful in tinnitus treatment and could even be harmful. However, the pharmacology of cannabinoids is very complex, and most studies focused on neural CB1R-based responses. Cannabinoid effects on the immune system (where CB2Rs predominate) are increasingly recognized as essential in understanding nervous system pathological responses, and data on immune cannabinoid targets have emerged in the auditory system as well. In addition, nonclassical cannabinoid targets (such as TRP channels) appear to play an important role in the auditory system as well. This review will focus on neuroimmunological mechanisms for cannabinoid effects and their possible use as protective and therapeutic agents in the ear and auditory system, especially in tinnitus.
Reduced Interhemispheric Coherence in Cerebellar Kainic Acid-Induced Lateralized Dystonia
Authors: Georgescu Margarint Elena Laura , Georgescu Ioana Antoaneta , Zahiu Carmen Denise Mihaela , Tirlea Stefan-Alexandru , Şteopoaie Alexandru Rǎzvan , Zǎgrean Leon , Popa Daniela , Zǎgrean Ana-Maria
Published: November 2020

The execution of voluntary muscular activity is controlled by the primary motor cortex, together with the cerebellum and basal ganglia. The synchronization of neural activity in the intracortical network is crucial for the regulation of movements. In certain motor diseases, such as dystonia, this synchrony can be altered in any node of the cerebello-cortical network. Questions remain about how the cerebellum influences the motor cortex and interhemispheric communication. This research aims to study the interhemispheric cortical communication between the motor cortices during dystonia, a neurological movement syndrome consisting of sustained or repetitive involuntary muscle contractions. We pharmacologically induced lateralized dystonia to adult male albino mice by administering low doses of kainic acid on the left cerebellar hemisphere. Using electrocorticography and electromyography, we investigated the power spectral densities, cortico-muscular, and interhemispheric coherence between the right and left motor cortices, before and during dystonia, for five consecutive days. Mice displayed lateralized abnormal motor signs, a reduced general locomotor activity, and a high score of dystonia. The results showed a progressive interhemispheric coherence decrease in low-frequency bands (delta, theta, beta) during the first 3 days. The cortico-muscular coherence of the affected side had a significant increase in gamma bands on days 3 and 4. In conclusion, lateralized cerebellar dysfunction during dystonia was associated with a loss of connectivity in the motor cortices, suggesting a possible cortical compensation to the initial disturbances induced by cerebellar left hemisphere kainate activation by blocking the propagation of abnormal oscillations to the healthy hemisphere. However, the cerebellum is part of several overly complex circuits, therefore other mechanisms can still be involved in this phenomenon.
CSF HIV RNA Escape in Opsoclonus-Myoclonus-Ataxia Syndrome: Case Report and Review of the Literature
Authors: Cabaraux Pierre , Poncelet Arthur , Honnorat Jérome , Demeester Remy , Cherifi Soraya , Manto Mario
Published: November 2020

Background: Human immunodeficiency viruses (HIV) infection is associated with a broad range of neurological manifestations, including opsoclonus-myoclonus ataxia syndrome (OMAS) occurring in primary infection, immune reconstitution syndrome or in case of opportunistic co-infection.

Case: We report the exceptional case of a 43-year-old female under HIV treatment for 10 years who presented initially with suspected epileptic seizure. Although the clinical picture slightly improved under anti-epileptic treatment, it was rapidly attributed to OMAS. The patient exhibited marked opsoclonus, mild dysarthria, upper limbs intermittent myoclonus, ataxia in 4 limbs, truncal ataxia, and a severe gait ataxia (SARA score: 34). The diagnostic work-up showed radiological and biological signs of central nervous system (CNS) inflammation and cerebral venous sinus thromboses. The HIV viral load was higher in cerebrospinal fluid (CSF) than in the blood (4,560 copies/ml vs. 76 copies/ml). She was treated for 5 days with pulsed corticotherapy. Dolutegravir and anticoagulation administration were initiated. Follow-ups at 2 and 4 months showed a dramatic improvement of clinical neurologic status (SARA score at 4 months: 1), reduction of CNS inflammation and revealed undetectable CSF and serum viral loads.

Conclusion: This case underlines the importance of the evaluation of the CSF viral load in HIV patients developing OMAS and suggests CSF HIV RNA escape as a novel cause for OMAS.
Clinical 3-D Gait Assessment of Patients With Polyneuropathy Associated With Hereditary Transthyretin Amyloidosis
Authors: Vilas-Boas Maria do Carmo , Rocha Ana Patrícia , Cardoso Márcio Neves , Fernandes José Maria , Coelho Teresa , Cunha João Paulo Silva
Published: November 2020

Hereditary amyloidosis associated with transthyretin V30M (ATTRv V30M) is a rare and inherited multisystemic disease, with a variable presentation and a challenging diagnosis, follow-up and treatment. This condition entails a definitive and progressive motor impairment that compromises walking ability from near onset. The detection of the latter is key for the disease's diagnosis. The aim of this work is to perform quantitative 3-D gait analysis in ATTRv V30M patients, at different disease stages, and explore the potential of the obtained gait information for supporting early diagnosis and/or stage distinction during follow-up. Sixty-six subjects (25 healthy controls, 14 asymptomatic ATTRv V30M carriers, and 27 symptomatic patients) were included in this case-control study. All subjects were asked to walk back and forth for 2 min, in front of a Kinect v2 camera prepared for body motion tracking. We then used our own software to extract gait-related parameters from the camera's 3-D body data. For each parameter, the main subject groups and symptomatic patient subgroups were statistically compared. Most of the explored gait parameters can potentially be used to distinguish between the considered group pairs. Despite of statistically significant differences being found, most of them were undetected to the naked eye. Our Kinect camera-based system is easy to use in clinical settings and provides quantitative gait information that can be useful for supporting clinical assessment during ATTRv V30M onset detection and follow-up, as well as developing more objective and fine-grained rating scales to further support the clinical decisions.
Natural Compounds With Antibacterial Activity Against Cronobacter spp. in Powdered Infant Formula: A Review
Authors: Polat Yemiş Gökçe , Delaquis Pascal
Published: November 2020

Bacteria from the genus Cronobacter are opportunistic foodborne pathogens capable of causing severe infections in neonates, the elderly and immunocompromised adults. The majority of neonatal infections have been linked epidemiologically to dehydrated powdered infant formulas (PIFs), the majority of which are manufactured using processes that do not ensure commercial sterility. Unfortunately, the osmotolerance, desiccation resistance, mild thermotolerance and wide-ranging minimum, optimum and maximum growth temperatures of Cronobacter spp. are conducive to survival and/or growth during the processing, reconstitution and storage of reconstituted PIFs. Consequently, considerable research has been directed at the development of alternative strategies for the control of Cronobacter spp. in PIFs, including approaches that employ antimicrobial compounds derived from natural sources. The latter include a range of phytochemicals ranging from crude extracts or essential oils derived from various plants (e.g., thyme, cinnamon, clove, marjoram, cumin, mint, fennel), to complex polyphenolic extracts (e.g., muscadine seed, pomegranate peel, olive oil, and cocoa powder extracts), purified simple phenolic compounds (e.g., carvacrol, citral, thymol, eugenol, diacetyl, vanillin, cinnamic acid, trans-cinnamaldehyde, ferulic acid), and medium chain fatty acids (monocaprylin, caprylic acid). Antimicrobials derived from microbial sources (e.g., nisin, other antibacterial peptides, organic acids, coenzyme Q0) and animal sources (e.g., chitosan, lactoferrin, antibacterial peptides from milk) have also been shown to exhibit antibacterial activity against the species. The selection of antimicrobials for the control of Cronobacter spp. requires an understanding of activity at different temperatures, knowledge about their mode of action, and careful consideration for toxicological and nutritional effects on neonates. Consequently, the purpose of the present review is to provide a comprehensive summary of currently available data pertaining to the antibacterial effects of natural antimicrobial compounds against Cronobacter spp. with a view to provide information needed to inform the selection of compounds suitable for control of the pathogen during the manufacture or preparation of PIFs by end users.
Physcion Protects Against Ethanol-Induced Liver Injury by Reprogramming of Circadian Clock
Authors: Yao Youli , Zuo Along , Deng Qiyu , Liu Shikang , Zhan Tianying , Wang Maolin , Xu Haidong , Ma Junxian , Zhao Yingying
Published: November 2020

The circadian clock plays a key role in our daily physiology and metabolism. Alcohol consumption disrupts the circadian rhythm of metabolic genes in the liver; however, the potential contribution of circadian clock modulation to alcoholic liver disease (ALD) is unknown. We identified a novel liver protective agent, physcion, which can alleviate fat accumulation and inflammation in ALD mice via reprogramming the hepatic circadian clock. The model of alcoholic hepatitis was established by intragastrically administering ethanol. In vitro, physcion was investigated by treating HepG2 cells with ethanol. The role of circadian clock in Physcion caused liver protection was tested by knocking down the core circadian gene Bmal1. Physcion application caused reduced lipogenesis and alleviated inflammation in alcohol-induced mice. In alcoholic hepatosteatosis models, physcion upregulated the core circadian genes. And the circadian misalignment triggered by ethanol was efficiently reversed by physcion. Physcion attenuated lipogenesis via reprogramming the circadian clock in HepG2 cells. Suppression of Bmal1 by RNA interference abolished the protective of physcion. In addition, Physcion binds to the active pocket of BMAL1 and promotes its expression. The study identified the novel liver protective effects of physcion on alcohol-induced liver injury, and modulation of the core circadian clock regulators contributes to ALD alleviation. More importantly, strategies targeting the circadian machinery, for example, Bmal1, may prove to be beneficial treatment options for this condition.