bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative Proteomic and Phosphoproteomic Analyses of Granulosa Cells During Follicular Atresia in Porcine
Authors: Yang Feng , Liu Qiang , Chen Yanhong , Ye Huizhen , Wang Han , Zeng Shenming
Published: January 2021

Ovarian follicular atresia is a natural physiological process; however, the mechanism is not fully understood. In this study, quantitative proteomic and phosphoproteomic analyses of granulosa cells (GCs) in healthy (H), slightly atretic (SA), and atretic follicles (A) of porcine were performed by TMT labeling, enrichment of phosphopeptides, and liquid chromatography with tandem mass spectrometry (LC–MS/MS) analysis. In total, 6,201 proteins were quantified, and 4,723 phosphorylation sites of 1,760 proteins were quantified. In total, 24 (11 up, 13 down) and 50 (29 up, 21 down) proteins with a fold change (FC) > 5 were identified in H/SA and H/A, respectively. In addition, there were 20 (H/SA, up) and 39 (H/A, up) phosphosites with an FC > 7 that could serve as potential biomarkers for distinguishing different quality categories of follicles. Western blotting and immunofluorescence confirmed the reliability of the proteomic analysis. Some key proteins (e.g., MIF, beta catenin, integrin β2), phosphosites (e.g., S76 of caspase6, S22 and S636 of lamin A/C), pathways (e.g., apoptosis, regulation of actin cytoskeleton pathway), transcription factors (e.g., STAT5A, FOXO1, and BCLAF1), and kinases (e.g., PBK, CDK5, CDK12, and AKT3) involved in the atresia process were revealedviafurther analysis of the differentially expressed proteins (DEPs) and phosphorylated proteins (DEPPs). Further study showed that mutant caspase6 Ser76 to Ala increased the ratios of cleaved caspase6/caspase6 and cleaved caspase3/caspase3 and dephosphorylation of caspase6 at Ser76 increased cell apoptotic rate, a new potential pathway of follicular atresia. Collectively, the proteomic and phosphoproteomic profiling and functional research in the current study comprehensively analyzed the dynamic changes in protein expression and phosphorylation during follicular atresia and provided some new explanations regarding the regulation of this process.
MicroRNA-505, Suppressed by Oncogenic Long Non-coding RNA LINC01448, Acts as a Novel Suppressor of Glycolysis and Tumor Progression Through Inhibiting HK2 Expression in Pancreatic Cancer
Authors: Xu Zhenglei , Zhang Dingguo , Zhang Zhuliang , Luo Weixiang , Shi Ruiyue , Yao Jun , Li Defeng , Wang Lisheng , Liao Bihong
Published: January 2021

Background: MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) play vital regulatory roles in pancreatic cancer (PC) initiation and progression. We aimed to explore the biological functions and underlying mechanisms of miR-505-3p (miR-505) in PC.

Methods: We first screened miRNA expression profiles using microarray in PC tissues and normal tissues, and then studied the function and underlying mechanism of miR-505. Moreover, we evaluated the regulatory effect of lncRNA LINC01448 on miR-505.

Results: We demonstrated miR-505 that was significantly downregulated in PC tissues. We further revealed that miR-505 significantly inhibited cell proliferation, invasion, sphere formation, glucose consumption, and lactate production by targeting HK2. In addition, overexpression of miR-505 led to tumor growth inhibition in vivo, demonstrating that it acts as a tumor suppressor in PC. LINC01448 was identified as an oncogenic lncRNA that could reduce miR-505 expression. Subsequent studies confirmed that LINC01448 enhanced cell proliferation, invasion, sphere formation, glucose consumption, and lactate production by regulating the miR-505/HK2 pathway.

Conclusions: These findings demonstrated that miR-505, suppressed by LINC01448, could function as a key tumor suppressor by targeting HK2 in PC, elucidating an important role of the LINC01448/miR-505/HK2 pathway in regulating PC glycolysis and progression.
Lanthanide-Doped Upconversion Nanoparticles for Super-Resolution Microscopy
Authors: Dong Hao , Sun Ling-Dong , Yan Chun-Hua
Published: January 2021

Super-resolution microscopy offers a non-invasive and real-time tool for probing the subcellular structures and activities on nanometer precision. Exploring adequate luminescent probes is a great concern for acquiring higher-resolution image. Benefiting from the atomic-like transitions among real energy levels, lanthanide-doped upconversion nanoparticles are featured by unique optical properties including excellent photostability, large anti-Stokes shifts, multicolor narrowband emissions, tunable emission lifetimes, etc. The past few years have witnessed the development of upconversion nanoparticles as probes for super-resolution imaging studies. To date, the optimal resolution reached 28 nm (λ/36) for single nanoparticles and 82 nm (λ/12) for cytoskeleton structures with upconversion nanoparticles. Compared with conventional probes such as organic dyes and quantum dots, upconversion nanoparticle-related super-resolution microscopy is still in the preliminary stage, and both opportunities and challenges exist. In this perspective article, we summarized the recent advances of upconversion nanoparticles for super-resolution microscopy and projected the future directions of this emerging field. This perspective article should be enlightening for designing efficient upconversion nanoprobes for super-resolution imaging and promote the development of upconversion nanoprobes for cell biology applications.
Getting Profitable CCU off the Ground: Contingent Pathways and Bergen Carbon Solutions
Authors: Sareen Siddharth , Sagmo Jan
Published: January 2021

As carbon capture utilization and storage (CCUS) gains policy traction and pilot project funding, CCS usually gets the limelight, whereas CCU is often overlooked. CCU, if feasible, has two potential advantages: it obviates risks and monitoring needs associated with long-term storage, and it creates economic value to offset carbon capture costs. Yet scholarly accounts of CCU feasibility are rare. To address this lacuna, the manuscript channels in-depth knowledge of a CCU start-up in Norway into a critical analysis of the barriers and opportunities for emerging sectoral enterprises. The trajectory of Bergen Carbon Solutions (BCS) during 2016–2019 is mapped by a human geographer along with its founder. We organize enquiry along three axes: (i) access to “soft” capital (this includes knowledge and human resources), (ii) access to “hard” capital (this includes financing and technical approvals), and (iii) navigation of rapid expansion. Under (i), we present and analyze the contextual conditions and contingencies for the emergence of the core value proposition. Under (ii), we detail the networks, processes, and institutional structures through which the enterprise gained its financial basis and was able to test its CCU process. Under (iii), we complement attention to organizational management by highlighting key informal and human factors. We foreground how the emergence of CCU is a relational process that depends on how actors in a changing field interact and reconfigure themselves. This informs regulatory policies and economic instruments about overlooked contextual issues related to the modulation and feasibility of scalable, profitable CCU.
A Specialized System-on-Chip Based Distance Protection for Distribution Grids with Inverter Interfaced Distributed Generation
Authors: Li Peng , Xi Wei , Yin Xianggen , Zeng Xiangjun , Li Licheng , Yang Qixun , Chen Wei
Published: January 2021

Legacy protection schemes face new challenges as Inverter Interfaced Distribution Generation (IIDG) significantly changes the transient fault response of the distribution grid. The performance of the protection near the IIDG side is adversely affected by Low Voltage Ride Through (LVRT) and the negative sequence current suppression control characteristics of the IIDG. The operational characteristics of the protection are very different from those of the legacy protection schemes used in the distribution grid. Traditional overcurrent protection schemes cannot meet the requirements of selectivity and sensitivity. This paper analyses the influence of the IIDG on the protection schemes used in the distribution grid. Based on the positive sequence voltage polarization impedance criterion this study proposes a polarizing impedance criterion based on the fault component of positive sequence voltage, which can adaptively follow the fault resistance variation to satisfy the requirements of grid operation. The simulation results show that: (a) the proposed criterion is immune to the adverse effects of the transient characteristics of the IIDG; and, (b) it can adaptively follow the change of fault resistance making it suitable for application in short distribution lines. Using specialized System-on-Chip technology, a new distance protection device has been developed and tested on an industrial site. Simulation results and field tests showed that the new distance protection meets the requirements of the distribution grid with IIDGs.
Identifying RBM47, HCK, CD53, TYROBP, and HAVCR2 as Hub Genes in Advanced Atherosclerotic Plaques by Network-Based Analysis and Validation
Authors: Liu Chiyu , Zhang Haifeng , Chen Yangxin , Wang Shaohua , Chen Zhiteng , Liu Zhaoyu , Wang Jingfeng
Published: January 2021

Background:Atherosclerotic cardiovascular diseases accounted for a quarter of global deaths. Most of these fatal diseases like coronary atherosclerotic disease (CAD) and stroke occur in the advanced stage of atherosclerosis, during which candidate therapeutic targets have not been fully established. This study aims to identify hub genes and possible regulatory targets involved in treatment of advanced atherosclerotic plaques.

Material/Methods:Microarray datasetGSE43292andGSE28829, both containing advanced atherosclerotic plaques group and early lesions group, were obtained from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was conducted to identify advanced plaque-related modules. Module conservation analysis was applied to assess the similarity of advanced plaque-related modules betweenGSE43292andGSE28829. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of these modules were performed by Metascape. Differentially expressed genes (DEGs) were mapped into advanced plaque-related modules and module membership values of DEGs in each module were calculated to identify hub genes. Hub genes were further validated for expression in atherosclerotic samples, for distinguishing capacity of CAD and for potential functions in advanced atherosclerosis.

Results:The lightgreen module (MElightgreen) inGSE43292and the brown module (MEbrown) inGSE28829were identified as advanced plaque-related modules. Conservation analysis of these two modules showed high similarity. GO and KEGG enrichment analysis revealed that genes in both MElightgreen and MEbrown were enriched in immune cell activation, secretory granules, cytokine activity, and immunoinflammatory signaling. RBM47, HCK, CD53, TYROBP, and HAVCR2 were identified as common hub genes, which were validated to be upregulated in advanced atherosclerotic plaques, to well distinguish CAD patients from non-CAD people and to regulate immune cell function-related mechanisms in advanced atherosclerosis.

Conclusions:We have identified RBM47, HCK, CD53, TYROBP, and HAVCR2 as immune-responsive hub genes related to advanced plaques, which may provide potential intervention targets to treat advanced atherosclerotic plaques.
Contributions and Prognostic Values of N6-Methyladenosine RNA Methylation Regulators in Hepatocellular Carcinoma
Authors: Qi Li-Wen , Jia Jian-Hui , Jiang Chen-Hao , Hu Jian-Ming
Published: January 2021

Introduction

The methylation at position N6 of adenine is called N6-methyladenosine (m6A). This transcriptional RNA modification exerts a very active and important role in RNA metabolism and in other biological processes. However, the activities of m6A associated with malignant liver hepatocellular carcinoma (LIHC) are unknown and are worthy of study.

Materials and Methods

Using the data of University of California, Santa Cruz (UCSC), the expression of M6A methylation regulators in pan-cancer was evaluated as a screening approach to identify the association of M6A gene expression and 18 cancer types, with a specific focus on LIHC. LIHC datasets of The Cancer Genome Atlas (TCGA) were used to explore the expression of M6A methylation regulators and their clinical significance. Gene Ontology (GO) analysis and Gene Set Enrichment Analysis (GSEA) were used to explore the underlying mechanism based on the evaluation of aberrant expression of m6A methylation regulators.

Results

The expression alterations of m6A-related genes varied across cancer types. In LIHC, we found that in univariate Cox regression analysis, up-regulated m6A modification regulators were associated with worse prognosis, except for ZC3H13. Kaplan–Meier survival curve analysis indicated that higher expression of methyltransferase-like protein 3 (METTL3) and YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) genes related to the worse survival rate defined by disease-related survival (DSS), overall survival (OS), progression-free interval (PFI), and disease-free interval (DFI). Up-regulated m6A methylation regulator group (cluster2) obtained by consensus clustering was associated with poor prognosis. A six-gene prognostic signature established using the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm performed better in the early (I + II; T1 + T2) stages than in the late (III + IV; T3 + T4) stages of LIHC. Using the gene signature, we constructed a risk score and found that it was an independent predictive factor for prognosis. Using GSEA, we identified processes involved in DNA damage repair and several biological processes associated with malignant tumors that were closely related to the high-risk group.

Conclusion

In summary, our study identified several genes associated with m6A in LIHC, especially METTL3 and YTHDF1, and confirmed that a risk signature comprised of m6A-related genes was able to forecast prognosis.
Immunosenescence Study of T Cells: A Systematic Review
Authors: Rodriguez Ivon Johanna , Lalinde Ruiz Nicolás , Llano León Manuela , Martínez Enríquez Laura , Montilla Velásquez María del Pilar , Ortiz Aguirre Juan Pablo , Rodríguez Bohórquez Oscar Mauricio , Velandia Vargas Esteban Alejandro , Hernández Edgar Debray , Parra López Carlos Alberto
Published: January 2021

Background

Aging is accompanied by alterations in immune response which leads to increased susceptibility to infectious diseases, cancer, autoimmunity, and inflammatory disorders. This decline in immune function is termed as immunosenescence; however, the mechanisms are not fully elucidated. Experimental approaches of adaptive immunity, particularly for T cells, have been the main focus of immunosenescence research. This systematic review evaluates and discusses T cell markers implicated in immunosenescence.

Objective

To determine the best flow cytometry markers of circulating T cells associated with immunosenescence.

Methods

We systematically queried PubMed, MEDLINE, EBSCO, and BVS databases for original articles focused on two age groups of healthy humans: 18–44 (young adults) and >60 (older adults) years. In accordance with the Cochrane methodology, we synthesized data through qualitative descriptions and quantitative random effects meta-analysis due to extensive heterogeneity.

Results

A total of 36 studies conducted in the last 20 years were included for the qualitative analysis and four out of these studies were used to perform the meta-analysis. A significant decrease in naïve T cell subset was observed in older adults compared to young adults. Primary markers used to identify senescent cells were loss of CD28 and increased expression of CD57 and KLRG1 in terminally-differentiated memory T cell subset in older adults. Moreover, we observed an increase in proinflammatory cytokines and decrease in telomere length in old adult T cells. It was not possible to perform quantitative synthesis on cell markers, cytokines, and telomere length because of the significant variations between the groups, which is attributed to differences in protocols and unreported measurements, thus generating a high risk of bias.

Conclusions

Heterogeneity among studies in terms of data report, measurement techniques and high risk of bias were major impediments for performing a robust statistical analysis that could aid the identification of eligible flow cytometry markers of immunosenescence phenotype in T cells.
Case Report: Variable Pharmacokinetic Profile of Eculizumab in an aHUS Patient
Authors: Bouwmeester Romy N. , Ter Avest Mendy , Wijnsma Kioa L. , Duineveld Caroline , ter Heine Rob , Volokhina Elena B. , Van Den Heuvel Lambertus P. W. J. , Wetzels Jack F. M. , van de Kar Nicole C. A. J.
Published: January 2021

Background

With the introduction of eculizumab, a C5-inhibitor, morbidity and mortality improved significantly for patients with atypical hemolytic uremic syndrome (aHUS). In view of the high costs, actual needs of the drug, and increasing evidence in literature, aHUS patients can be treated according to a restrictive eculizumab regimen. We retrospectively analyzed the pharmacokinetic and dynamic parameters of eculizumab in one patient in time, emphasizing various factors which could be taken into account during tapering of treatment.

Case Presentation

A nowadays 18-year-old male with a severe, frequently relapsing form of atypical HUS due to a hybrid CFH/CFHR1 gene in combination with the homozygous factor H haplotype, required chronic plasma therapy (PT), including periods with plasma infusion, from the age of onset at 5 months until initiation of eculizumab at the age of 11 years. A mild but stable chronic kidney disease (CKD) and 9 years of disease remission enabled prolongation of eculizumab interval. At the age of 15 years, a sudden yet multifactorial progression of chronic kidney disease (CKD) was observed, without any signs of disease recurrence. However, an acquired glomerulocystic disease, a reduced left kidney function, and abnormal abdominal venous system of unknown etiology were found. In addition, after an aHUS relapse, an unexpected increase in intra-patient variability of eculizumab concentrations was seen. Retrospective pharmacokinetic analysis revealed a change in eculizumab clearance, associated with a simultaneous increase in proteinuria.

Conclusion

High intra-patient variability of eculizumab pharmacokinetics were observed over time, emphasizing the necessity for adequate and continuous therapeutic drug monitoring in aHUS patients. Eculizumab serum trough levels together with complement activation markers (CH50) should be frequently assessed, especially during tapering of drug therapy and/or changing clinical conditions in the patient. In addition, an increase in proteinuria could result in urinary eculizumab loss, indicating that urinary monitoring of eculizumab may be important in aHUS patients with an unexplained decline in serum concentrations.
Dirty Fish Versus Squeaky Clean Mice: Dissecting Interspecies Differences Between Animal Models of Interferonopathy
Authors: Rutherford Holly A. , Kasher Paul R. , Hamilton Noémie
Published: January 2021

Autoimmune and autoinflammatory diseases are rare but often devastating disorders, underpinned by abnormal immune function. While some autoimmune disorders are thought to be triggered by a burden of infection throughout life, others are thought to be genetic in origin. Among these heritable disorders are the type I interferonopathies, including the rare Mendelian childhood-onset encephalitis Aicardi-Goutières syndrome. Patients with Aicardi Goutières syndrome are born with defects in enzymes responsible for nucleic acid metabolism and develop devastating white matter abnormalities resembling congenital cytomegalovirus brain infection. In some cases, common infections preceded the onset of the disease, suggesting immune stimulation as a potential trigger. Thus, the antiviral immune response has been actively studied in an attempt to provide clues on the pathological mechanisms and inform on the development of therapies. Animal models have been fundamental in deciphering biological mechanisms in human health and disease. Multiple rodent and zebrafish models are available to study type I interferonopathies, which have advanced our understanding of the human disease by identifying key pathological pathways and cellular drivers. However, striking differences in phenotype have also emerged between these vertebrate models, with zebrafish models recapitulating key features of the human neuropathology often lacking in rodents. In this review, we compare rodent and zebrafish models, and summarize how they have advanced our understanding of the pathological mechanisms in Aicardi Goutières syndrome and similar disorders. We highlight recent discoveries on the impact of laboratory environments on immune stimulation and how this may inform the differences in pathological severity between mouse and zebrafish models of type I interferonopathies. Understanding how these differences arise will inform the improvement of animal disease modeling to accelerate progress in the development of therapies for these devastating childhood disorders.
Emergence of 16S rRNA Methylase Gene rmtB in Salmonella Enterica Serovar London and Evolution of RmtB-Producing Plasmid Mediated by IS26
Authors: Wang Jing , Wang Zhen-Yu , Wang Yan , Sun Fan , Li Wei , Wu Han , Shen Peng-Cheng , Pan Zhi-Ming , Jiao Xinan
Published: January 2021

This study aimed to characterize 16S rRNA methylase genes among Salmonella and to elucidate the structure and evolution of rmtB-carrying plasmids. One hundred fifty-eight Salmonella isolates from one pig slaughterhouse were detected as containing 16S rRNA methylase genes; two (1.27%) Salmonella London isolates from slaughtered pigs were identified to carry rmtB. They were resistant to gentamicin, amikacin, streptomycin, ampicillin, tetracycline, florfenicol, ciprofloxacin, and sulfamethoxazole/trimethoprim. The complete sequences of RmtB-producing isolates were obtained by PacBio single-molecule real-time sequencing. The isolate HA1-SP5 harbored plasmids pYUHAP5-1 and pYUHAP5-2. pYUHAP5-1 belonged to the IncFIBK plasmid and showed high similarity to multiple IncFIBK plasmids from Salmonella London in China. The rmtB-carrying plasmid pYUHAP5-2 contained a typical IncN-type backbone; the variable region comprising several resistance genes and an IncX1 plasmid segment was inserted in the resolvase gene resP and bounded by IS26. The sole plasmid in HA3-IN1 designated as pYUHAP1 was a cointegrate of plasmids from pYUHAP5-1-like and pYUHAP5-2-like, possibly mediated by IS26 via homologous recombination or conservative transposition. The structure differences between pYUHAP1 and its corresponding part of pYUHAP5-1 and pYUHAP5-2 may result from insertion, deletion, or recombination events mediated by mobile elements (IS26, ISCR1, and ISKpn43). This is the first report of rmtB in Salmonella London. IncN plasmids are efficient vectors for rmtB distribution and are capable of evolving by reorganization and cointegration. Our results further highlight the important role of mobile elements, particularly IS26, in the dissemination of resistance genes and plasmid evolution.
Long Non-coding RNAs in Gammaherpesvirus Infections: Their Roles in Tumorigenic Mechanisms
Authors: Liu Wen , Zhang Yan , Luo Bing
Published: January 2021

Long non-coding RNAs (lncRNAs) regulate gene expression at the epigenetic, transcriptional, or posttranscriptional level by interacting with protein, DNA, and RNA. Emerging evidence suggests that various lncRNAs are abnormally expressed and play indispensable roles in virus-triggered cancers. Besides, a growing number of studies have shown that virus-encoded lncRNAs participate in tumorigenesis. However, the functions of most lncRNAs in tumors caused by oncogenic viruses and their underlying mechanisms remain largely unknown. In this review, we summarize current findings regarding lncRNAs involved in cancers caused by Epstein–Barr virus (EBV) and Kaposi’s sarcoma herpesvirus (KSHV). Additionally, we discuss the contribution of lncRNAs to tumor occurrence, development, invasion, and metastasis; the roles of lncRNAs in key signaling pathways and their potential as biomarkers and therapeutic targets for tumor diagnostics and treatment.
Gemmatimonas groenlandica sp. nov. Is an Aerobic Anoxygenic Phototroph in the Phylum Gemmatimonadetes
Authors: Zeng Yonghui , Nupur  , Wu Naicheng , Madsen Anne Mette , Chen Xihan , Gardiner Alastair T. , Koblížek Michal
Published: January 2021

The bacterial phylum Gemmatimonadetes contains members capable of performing bacteriochlorophyll-based phototrophy (chlorophototrophy). However, only one strain of chlorophototrophic Gemmatimonadetes bacteria (CGB) has been isolated to date, hampering our further understanding of their photoheterotrophic lifestyle and the evolution of phototrophy in CGB. By combining a culturomics strategy with a rapid screening technique for chlorophototrophs, we report the isolation of a new member of CGB,Gemmatimonas (G.) groenlandicasp. nov., from the surface water of a stream in the Zackenberg Valley in High Arctic Greenland. Distinct from the microaerophilicG. phototrophicastrain AP64T,G. groenlandicastrain TET16Tis a strictly aerobic anoxygenic phototroph, lacking many oxygen-independent enzymes while possessing an expanded arsenal for coping with oxidative stresses. Its pigment composition and infra-red absorption properties are also different fromG. phototrophica, indicating that it possesses a different photosystem apparatus. The complete genome sequence ofG. groenlandicareveals unique and conserved features in the photosynthesis gene clusters of CGB. We further analyzed metagenome-assembled genomes of CGB obtained from soil and glacier metagenomes from Northeast Greenland, revealing a wide distribution pattern of CGB beyond the stream water investigated.
AtxA-Controlled Small RNAs of Bacillus anthracis Virulence Plasmid pXO1 Regulate Gene Expression in trans
Authors: Corsi Ileana D. , Dutta Soumita , van Hoof Ambro , Koehler Theresa M.
Published: January 2021

Small regulatory RNAs (sRNAs) are short transcripts that base-pair to mRNA targets or interact with regulatory proteins. sRNA function has been studied extensively in Gram-negative bacteria; comparatively less is known about sRNAs in Firmicutes. Here we investigate two sRNAs encoded by virulence plasmid pXO1 of Bacillus anthracis, the causative agent of anthrax. The sRNAs, named “XrrA and XrrB” (for pXO1-encoded regulatory RNA) are abundant and highly stable primary transcripts, whose expression is dependent upon AtxA, the master virulence regulator of B. anthracis. sRNA levels are highest during culture conditions that promote AtxA expression and activity, and sRNA levels are unaltered in Hfq RNA chaperone null-mutants. Comparison of the transcriptome of a virulent Ames-derived strain to the transcriptome of isogenic sRNA-null mutants revealed multiple 4.0- to >100-fold differences in gene expression. Most regulatory effects were associated with XrrA, although regulation of some transcripts suggests functional overlap between the XrrA and XrrB. Many sRNA-regulated targets were chromosome genes associated with branched-chain amino acid metabolism, proteolysis, and transmembrane transport. Finally, in a mouse model for systemic anthrax, the lungs and livers of animals infected with xrrA-null mutants had a small reduction in bacterial burden, suggesting a role for XrrA in B. anthracis pathogenesis.
Genomic Insights Into the Antifungal Activity and Plant Growth-Promoting Ability in Bacillus velezensis CMRP 4490
Authors: Teixeira Gustavo Manoel , Mosela Mirela , Nicoletto Maria Luiza Abreu , Ribeiro Renan Augusto , Hungria Mariangela , Youssef Khamis , Higashi Allan Yukio , Mian Silas , Ferreira André Sampaio , Gonçalves Leandro Simões Azeredo , Pereira Ulisses de Padua , de Oliveira Admilton Gonçalves
Published: January 2021

The main objective of this study was to evaluate Bacillus velezensis strain CMRP 4490 regarding its ability to inhibit soil-borne plant pathogens and to increase plant growth. The study included evaluation of in vitro antifungal control, sequencing the bacterial genome, mining genes responsible for the synthesis of secondary metabolites, root colonization ability, and greenhouse studies for the assessment of plant growth–promoting ability. The strain was obtained from soil samples in the north of Paraná in Brazil and was classified as a B. velezensis, which is considered a promising biological control agent. In vitro assay showed that B. velezensis CMRP 4490 presented antagonistic activity against Sclerotinia sclerotiorum, Macrophomina phaseolina, Botrytis cinerea, and Rhizoctonia solani with a mycelial growth inhibition of approximately 60%, without any significant difference among them. To well understand this strain and to validate its effect on growth-promoting rhizobacteria, it was decided to explore its genetic content through genome sequencing, in vitro, and greenhouse studies. The genome of CMRP 4490 was estimated at 3,996,396 bp with a GC content of 46.4% and presents 4,042 coding DNA sequences. Biosynthetic gene clusters related to the synthesis of molecules with antifungal activity were found in the genome. Genes linked to the regulation/formation of biofilms, motility, and important properties for rhizospheric colonization were also found in the genome. Application of CMRP 4490 as a coating film on soybean increased from 55.5 to 64% on germination rates when compared to the control; no differences were observed among treatments for the maize germination. The results indicated that B. velezensis CMRP 4490 could be a potential biocontrol agent with plant growth–promoting ability.
Factors Associated With Prosthesis Embodiment and Its Importance for Prosthetic Satisfaction in Lower Limb Amputees
Authors: Bekrater-Bodmann Robin
Published: January 2021

Perceptual integration of a prosthesis into an amputee's body representation, that is, prosthesis embodiment, has been proposed to be a major goal of prosthetic treatment, potentially contributing to the user's satisfaction with the device. However, insufficient knowledge about individual or prosthetic factors associated with prosthesis embodiment challenges basic as well as rehabilitation research. In the present study, hierarchical multiple regression analyses on prosthesis embodiment—as assessed with the recently introduced Prosthesis Embodiment Scale—were applied to the survey data of a large sample of prosthesis-using lower limb amputees, entering relevant objective-descriptive (i.e., unbiased characteristics of the amputation or the prosthesis) and subjective-evaluative variables (i.e., the amputee's perceptions related to the amputation or the prosthesis) as first- or second-level regressors, respectively. Significant regressors identified in these analyses together explained R2 = 36.3% of prosthesis embodiment variance in the present sample, with a lower level of amputation, less intense residual limb pain, more realistic visual appearance of the device, higher prosthetic mobility, and more positive valence of prosthesis-induced residual limb stimulations representing significantly associated factors. Using the identical set of regressors hierarchically complemented by prosthesis embodiment on measures of prosthetic satisfaction—as assessed with the Trinity Amputation and Prosthesis Experience Scales—revealed that prosthesis embodiment was significantly and positively associated with aesthetic as well as functional prosthesis satisfaction. These findings emphasize the importance of psychological factors for the integration of a prosthesis into the amputee's body representation, which itself represents a crucial factor associated with prosthesis satisfaction. The results might have important implications for future prosthetic treatment; however, replication of the findings in an independent sample is required, as well as sophisticated experimental designs in order to elucidate the causality of effects.
Design and Development of a Virtual Reality-Based Mobility Training Game for People With Parkinson's Disease
Authors: Finley James M. , Gotsis Marientina , Lympouridis Vangelis , Jain Shreya , Kim Aram , Fisher Beth E.
Published: January 2021

People with Parkinson's disease (PD) commonly have gait impairments that reduce their ability to walk safely in the community. These impairments are characterized, in part, by a compromised ability to turn and negotiate both predictable and unpredictable environments. Here, we describe the development and usability assessment of a virtual reality training application, Wordplay VR, that allows people with PD to practice skills such as turning, obstacle avoidance, and problem-solving during over-ground walking in a game-based setting. Nine people with PD completed three sessions with Wordplay VR, and each session was directed by their personal physical therapist. Our outcome measures included perceived sense of presence measured using the International Test Commission–Sense of Presence Inventory (ITC-SOPI), levels of motivation using the Intrinsic Motivation Inventory (IMI), overall system usability using the System Usability Scale (SUS), and setup time by the physical therapists. Both the people with PD and the physical therapists rated their sense of presence in the training system positively. The system received high ratings on the interest and value subscales of the IMI, and the system was also rated highly on usability, from the perspective of both the patient during gameplay and the therapist while controlling the experience. These preliminary results suggest that the application and task design yielded an experience that was motivating and user-friendly for both groups. Lastly, with repeated practice over multiple sessions, therapists were able to reduce the time required to help their patients don the headset and sensors and begin the training experience.
The National Institutes of Health COVID-19 NeuroDatabank and NeuroBiobank: A National Resource for Learning, Discovery, and Progress
Authors: Troxel Andrea B. , Frontera Jennifer A. , Mendoza-Puccini Carolina
Published: January 2021

Patients suffering from COVID-19 experience a wide range of symptoms and sequelae, including increasingly recognized neurological problems. A concerted effort is necessary to identify and characterize these issues, whether newly appearing as a result of COVID-19 disease or exacerbations of underlying conditions. A national resource to collect information and/or biospecimens regarding neurological complications of COVID-19 offers an opportunity for broad representation, harmonization, and rapid learning, all while ensuring robust protection of confidential information through the use of global unique identifiers to protect patient privacy.
Rehabilitation and Biomarkers of Stroke Recovery: Study Protocol for a Randomized Controlled Trial
Authors: Picelli Alessandro , Filippetti Mirko , Del Piccolo Lidia , Schena Federico , Chelazzi Leonardo , Della Libera Chiara , Donadelli Massimo , Donisi Valeria , Fabene Paolo Francesco , Fochi Stefania , Fonte Cristina , Gandolfi Marialuisa , Gomez-Lira Macarena , Locatelli Elena , Malerba Giovanni , Mariotto Sofia , Milanese Chiara , Patuzzo Cristina , Romanelli Maria Grazia , Sbarbati Andrea , Tamburin Stefano , Venturelli Massimo , Zamparo Paola , Carcereri de Prati Alessandra , Butturini Elena , Varalta Valentina , Smania Nicola
Published: January 2021

Background: Stroke is a leading cause of disability. Nonetheless, the care pathway for stroke rehabilitation takes partially into account the needs of chronic patients. This is due in part to the lack of evidence about the mechanisms of recovery after stroke, together with the poor knowledge of related and influencing factors. Here we report on the study protocol “Rehabilitation and Biomarkers of Stroke Recovery,” which consists of 7 work-packages and mainly aim to investigate the effects of long-term neurorehabilitation on stroke patients and to define a related profile of (clinical-biological, imaging, neurophysiological, and genetic-molecular) biomarkers of long-term recovery after stroke. The work-package 1 will represent the main part of this protocol and aims to compare the long-term effects of intensive self-rehabilitation vs. usual (rehabilitation) care for stroke.

Methods: We planned to include a total of 134 adult subacute stroke patients (no more than 3 months since onset) suffering from multidomain disability as a consequence of first-ever unilateral ischemic stroke. Eligible participants will be randomly assigned to one of the following groups: intensive self-rehabilitation (based on the principles of “Guided Self-Rehabilitation Contract”) vs. usual care (routine practice). Treatment will last 1 year, and patients will be evaluated every 3 months according to their clinical presentation. The following outcomes will be considered in the main work-package: Fugl-Meyer assessment, Cognitive Oxford Screen Barthel Index, structural and functional neuroimaging, cortical excitability, and motor and somatosensory evoked potentials.

Discussion: This trial will deal with the effects of an intensive self-management rehabilitation protocol and a related set of biomarkers. It will also investigate the role of training intensity on long-term recovery after stroke. In addition, it will define a set of biomarkers related to post-stroke recovery and neurorehabilitation outcome in order to detect patients with greater potential and define long-term individualized rehabilitation programs.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04323501.
Physical Activity Improves Anxiety and Apathy in Early Parkinson's Disease: A Longitudinal Follow-Up Study
Authors: Ng Samuel Yong-Ern , Chia Nicole Shuang-Yu , Abbas Mirza Masoom , Saffari Ehsan Seyed , Choi Xinyi , Heng Dede Liana , Xu Zheyu , Tay Kay-Yaw , Au Wing-Lok , Tan Eng-King , Tan Louis Chew-Seng
Published: January 2021

Objective: In a prospective study, we investigated the association between physical activity and various motor, non-motor outcomes, and quality of life in early Parkinson's disease (PD) participants in the PD Longitudinal Singapore Study.

Background: Prospective studies that examined the association between physical activity and motor and non-motor domains in early PD are lacking.

Methods: 121 PD participants were followed-up prospectively to evaluate the association of physical activity with various symptom domains. The Physical Activity Scale for the Elderly (PASE) was used to measure physical activity annually. PD-related symptoms were categorized by motor, non-motor, and quality of life measures. Multivariate regression with gain score analysis was performed to understand the association of baseline PASE scores with the change of each variable at 1-year follow-up.

Results: Higher baseline PASE scores (greater activity) were associated with a younger age, lower MDS-UPDRS motor scores, a smaller levodopa equivalent daily dose, better attention and memory scores, and better QoL. Activity scores in early PD declined on follow-up. Multivariate analysis revealed higher baseline physical activity to be associated with decreased anxiety and apathy scores at 1-year follow-up, after adjusting for demographic variables and medications.

Conclusion: We demonstrated that higher baseline physical activity was associated with improved anxiety and apathy symptoms in early PD over a 1-year period.
Increased Amygdala-Paracentral Lobule/Precuneus Functional Connectivity Associated With Patients With Mood Disorder and Suicidal Behavior
Authors: Zhang Ran , Zhang Luheng , Wei Shengnan , Wang Pengshuo , Jiang Xiaowei , Tang Yanqing , Wang Fei
Published: January 2021

Mood disorder patients have greater suicide risk than members of the general population, but how suicidal behavior relates to brain functions has not been fully elucidated. This study investigated how functional connectivity (FC) values between the right/left amygdala and the whole brain relate to suicidal behavior in patients with mood disorder. The participants in this study were 100 mood disorder patients with suicidal behavior (SB group), 120 mood disorder patients with non-suicidal behavior (NSB group), and 138 age- and gender-matched healthy controls (HC group). Whole-brain FC values among the three groups were compared using an analysis of covariance (ANCOVA). Compared to the NSB and HC groups, increased FC values in the right amygdala-bilateral paracentral lobule/precuneus circuit were observed in the SB group (Bonferroni-corrected,p< 0.017). The FC values in the NSB group did not differ significantly from those in the HC group (Bonferroni-corrected,p> 0.017). Moreover, there were no significant differences in FC values between mood disorder patients with suicide attempt (SA group) and mood disorder patients with suicidal ideation (SI group), while the FC values between the right amygdala and bilateral paracentral lobule/precuneus in the SA group were higher than the mean in the SI group. These findings suggest that right amygdala-paracentral lobule/precuneus dysfunction has an important role in patients with mood disorder and suicidal behavior.
Lessons From Deep Neural Networks for Studying the Coding Principles of Biological Neural Networks
Authors: Bae Hyojin , Kim Sang Jeong , Kim Chang-Eop
Published: January 2021

One of the central goals in systems neuroscience is to understand how information is encoded in the brain, and the standard approach is to identify the relation between a stimulus and a neural response. However, the feature of a stimulus is typically defined by the researcher's hypothesis, which may cause biases in the research conclusion. To demonstrate potential biases, we simulate four likely scenarios using deep neural networks trained on the image classification dataset CIFAR-10 and demonstrate the possibility of selecting suboptimal/irrelevant features or overestimating the network feature representation/noise correlation. Additionally, we present studies investigating neural coding principles in biological neural networks to which our points can be applied. This study aims to not only highlight the importance of careful assumptions and interpretations regarding the neural response to stimulus features but also suggest that the comparative study between deep and biological neural networks from the perspective of machine learning can be an effective strategy for understanding the coding principles of the brain.
Resveratrol Attenuates High-Fat Diet Induced Hepatic Lipid Homeostasis Disorder and Decreases m6A RNA Methylation
Authors: Wu Jiamin , Li Yi , Yu Jiayao , Gan Zhending , Wei Wenyao , Wang Chao , Zhang Lili , Wang Tian , Zhong Xiang
Published: January 2021

Purpose:N6-methyladenosine (m6A) mRNA methylation is affected by dietary factors and associated with lipid metabolism; however, whether the regulatory role of resveratrol in lipid metabolism is involved in m6A mRNA methylation remains unknown. Here, the objective of this study was to investigate the effect of resveratrol on hepatic lipid metabolism and m6A RNA methylation in the liver of mice.

Methods: A total of 24 male mice were randomly allocated to LFD (low-fat diet), LFDR (low-fat diet + resveratrol), HFD (high-fat diet), and HFDR (high-fat diet + resveratrol) groups for 12 weeks (n = 6/group). Final body weight of mice was measured before sacrificing. Perirhemtric fat, abdominal and epididymal fat, liver tissues, and serum were collected at sacrifice and analyzed. Briefly, mice phenotype, lipid metabolic index, and m6A modification in the liver were assessed.

Results: Compared to the HFD group, dietary resveratrol supplementation reduced the body weight and relative abdominal, epididymal, and perirhemtric fat weight in high-fat-exposed mice; however, resveratrol significantly increased average daily feed intake in mice given HFD. The amounts of serum low-density lipoprotein cholesterol (LDL), liver total cholesterol (TC), and triacylglycerol (TAG) were significantly decreased by resveratrol supplementation. In addition, resveratrol significantly enhanced the levels of peroxisome proliferator-activated receptor alpha (PPARα), peroxisome proliferator-activated receptor beta/delta (PPARβ/δ), cytochrome P450, family 4, subfamily a, polypeptide 10/14 (CYP4A10/14), acyl-CoA oxidase 1 (ACOX1), and fatty acid-binding protein 4 (FABP4) mRNA and inhibited acyl-CoA carboxylase (ACC) mRNA levels in the liver. Furthermore, the resveratrol in HFD increased the transcript levels of methyltransferase like 3 (METTL3), alkB homolog 5 (ALKBH5), fat mass and obesity associated protein (FTO), and YTH domain family 2 (YTHDF2), whereas it decreased the level of YTH domain family 3 (YTHDF3) and m6A abundance in mice liver.

Conclusion: The beneficial effect of resveratrol on lipid metabolism disorder under HFD may be due to decrease of m6A RNA methylation and increase of PPARα mRNA, providing mechanistic insights into the function of resveratrol in alleviating the disturbance of lipid metabolism in mice.
An Integrated Strategy for Effective-Component Discovery of Astragali Radix in the Treatment of Lung Cancer
Authors: Yang Bing , Yang Nan , Chen Yaping , Zhu Maomao , Lian Yuanpei , Xiong Zhiwei , Wang Bei , Feng Liang , Jia Xiaobin
Published: January 2021

Lung cancer is one of the most devastating diseases worldwide, with high incidence and mortality worldwide, and the anticancer potential of traditional Chinese medicine (TCM) has been gradually recognized by the scientific community. Astragali Radix (AR) is commonly used in traditional Chinese medicine in the treatment of lung cancer and has a certain clinical effect, but effective components and targets are still unclear. In the study, we established an integrated strategy for effective-component discovery of AR in the treatment of lung cancer based on a variety of techniques. First, the effective components and potential targets of AR were deciphered by the “component-target-disease” network using network pharmacology, and potential signal pathways on lung cancer were predicted by Gene Ontology (GO) biological function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Then, the therapeutic effects of AR in the treatment of lung cancer were evaluated in vivo using A/J mice, and the potential targets related to autophagy and potential signal pathway were verified by Western blot analysis, immunofluorescence staining, and real-time PCR technology at protein and gene expression level. Finally, metabolism in vitro by rat intestinal flora and cell membrane immobilized chromatography technology were used to screen the effective components of AR in the treatment of lung cancer, and remaining components from the cell immobilized chromatography were collected and analyzed by ultra-performance liquid chromatography–electrospray quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The screening results of the integrated strategy showed that calycosin-7-O-β-D-glucoside, ononin, calycosin, astragaloside IV, astragaloside II, cycloastragenol, and formononetin may be effective components of AR in the treatment of lung cancer, and they may play a role in the treatment of lung cancer through autophagy and p53/AMPK/mTOR signaling pathway. The integrated strategy for effective-component discovery provided a valuable reference mode for finding the pharmacodynamic material basis of complex TCM systems. In addition, the prediction for targets and signal pathways laid a foundation for further study on the mechanism of AR in the treatment of lung cancer.