bluuebunny/crossref_metadata_2025 huggingface dataset:
Social by Definition: How Users Define Social Platforms and Why It Matters
Authors: Rhee Lisa , Bayer Joseph , Lee David , Kuru Ozan
Published: March 2021

Social media platforms are characterized by diverse features and functions, and these facets remain in constant flux over time. This research examines how users define the central purpose of four major platforms in the United States (Facebook, Twitter, Instagram, Snapchat), and how such lay definitions relate to key outcomes previously associated with social media use. In Study 1, we validated self-report measures using a comparative scaling approach to capture what users view as the most defining categories of the four platforms. In Study 2, we investigated whether lay definitions of platforms relate to perceptions of social affordances and social resources. Overall, results provided evidence that defining platforms as social interaction (vs. other categories) is associated with amplified social affordances and resources. Together, the studies contribute to our understanding of how users navigate a dynamic online ecosystem, as well as how lay definitions may anchor the experiences and effects of social media.
Breakdown of Injuries and Their Consequences in Previously Operated Eyes
Authors: Sobianin N. A. , Arshina Y. A. , Petropavlovskaya L. G. , Gavrilova T. V.
Published: March 2021

Aim. To analyze injuries and their consequences in patients who previously underwent eye surgery.

Materials and Methods. We carried out a retrospective analysis of case histories of 34 patients (35 eyes) who had previously undergone ophthalmic surgery and were re-hospitalized due to an eye injury sustained between several days to 23 years after surgery. There were 18 male and 16 female patients; 59% of them were of retirement age.

Results . Half of the patients sustained injuries within 6 months after surgery. Fifteen patients sought medical attention on the same date. Civilian traumas prevailed and occurred in 33 patients; 10 patients out of them sustained criminal injury. Polytrauma occured in 4 patients. Primary blast injury occurred in 3% of patients, while secondary and tertiary blast injuries occurred in 14% and 83% of patients respectively. Intraocular infection developed in 6% of the injured patients and 33 eyes required an emergency surgical treatment. Visual acuity depended on the severity of the injury and its baseline after previous surgical treatment. On admission, blindness and low spatial vision were diagnosed in 85% cases and persisted at discharge in 77% of cases. Hypotension diagnosed in 83% of cases persisted at discharge in 31% of cases. After maximum access surgeries, especially extracapsular cataract extractions, a tertiary blast injury was discovered in 22 eyes. In these patients, visual acuity was below 0.09 (decimal system); at discharge, it remained the same in 73% of patients. Further rehabilitation was indicated for 80% of patients.

Summary. Injuries of the previously operated eyes were blast-induced and had a varying severity. Their occurrence in male and female patients was roughly equivalent. Injuries occurred more often in patients of retirement age; for the most part, they were sustained during off the job circumstances. Patients requested for ophthalmological treatment late and required a long-term medical and social rehabilitation as their injuries were accompanied by a significant decrease in visual functions.
Color testing and color correction
Authors: Abugova T. D.
Published: March 2021

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A brief report on National Coordinated Varietal Trials (NCVT) of Cotton conducted by Pakistan Central Cotton Committee (PCCC) during the season 2018
Authors: Ahsan Muhammad Zahir , Afzal Hamza , Soomro Abdul Razaque
Published: March 2021

National Coordinated Varietal Trial was conducted to evaluate the performance of the new strains for yield potential and stability. Multi-location trial consisting of 121 strains was carried out at 13 locations under different agro-climatic zones. So different genotypes behaved differently as environment was changed hence none of the genotype was found stable in any environment. Gene expression profiling was done from four designated labs. The presence of gene and trait purity was done through event specific primers in PCR and quantities profiling was conducted by ELISA test. Most of the strains showed low purity level as well as low toxin level compared to the EPA-USA recommendation (1.5μg/g). The strains claimed as non-Bt by the respective breeder also showed the presence of Bt toxins. Hence the information is very useful for breeders as well as for other cotton stakeholders to be careful while developing high yielding varieties adoptive to multi-environment and with recommended dose of toxin level. It will also be helpful for variety registration/approval and extension department for giving general and specific recommendations of crop production
An Overview of factors affecting on cotton production
Authors: Soomro Abdul Wahab , Keerio Abdullah , Khuhro Shah Nawaz
Published: March 2021

Cotton is well prominent as “white gold” an important cash and precious crop in overall cotton growing development counties. The yield of this crop is depending upon the environment in which it is grown and management practices of the cropping system. It is noted after review of various publications of scientists that several factors are responsible which affecting cotton production, selection of cultivar should be according to environment in which it is grown, soil preparation, seed rate, plant spacing, sowing/planting dates and timely irrigation are the important factors which effect on yield. Whereas, nutrients management and crop protections are the key factors which directly affecting the plant growth and development ultimately directly responsible for decreasing yield. Along with these factors modern technology and farmer’s education play a vital role for producing quality cotton production and management of farms. Therefore, suggested that farmers should apply better management practices and follow proper time management as per practices and apply timely appropriate inputs for crop growth and development and crop protection measures for sustainable cotton production.
Evaluation of high yielding candidate cotton genotypes tested in National Coordinated Varietal Trial at different locations of Sindh and Balochistan
Authors: Ahmed Sultan
Published: March 2021

The research was conducted during the two consecutive years 2018 and 2019; twenty eight (28) advance cotton strains were tested in national coordinated varietal trials (NCVT) at seven locations of Sindh and Balochistan. The results revealed highly significant difference among the varieties during both the years. On the basis of two years average performance only two candidate strains GH-Uhad and NIAB-135 showed their stability in yield performance during both the years. Therefore, it is recommended that top two high yielding varieties (GH-Uhad and NIAB-135) with stability in performance must be approved by the provincial seed council of Sindh and Balochistan to revive the cotton production of the provinces as well as national economy and not to waste/garbage this high yielding stuff and also suggested to cotton breeders utilization in hybridization/breeding program to evolve high yield variety.
Evaluation of different cotton varieties against drought tolerance: A comparative analysis
Authors: Ullah Aziz , Shakeel Amir , Ahmed Hafiz Ghulam Muhu-Din , Yar Muhammad Majid , Ali Muhammad
Published: March 2021

The limited water supply for irrigation is a major constraint to cotton production. Morphological and physiological traits provide useful information for drought tolerance. This research work was carried out for the identification of cotton genotypes having better drought tolerance. For this purpose, forty (40) genotypes of upland cotton were studied under two moisture regime, i.e. normal and drought environment in field conditions. The experiment was conducted using split plot design under RCBD arrangement. All the genotypes behaved differently under two moisture levels. The interaction of cotton genotypes with two moisture levels were studied for various traits, i.e. plant height, sympodial branches, seed cotton yield, boll weight, number of bolls per plant, excised leaf water loss and relative water content by using Principle Component Analysis (PCA). Results showed that the genotypes VH-144, IUB-212, MNH-886, VH-295, IR-3701, AA-802, NIAB-111, NS-121, FH-113, and FH-142 are either stable or showing positive interaction with drought conditions for most of the traits under studied. These genotypes can be used in further breeding program for developing varieties suitable for cultivation under drought conditions, whereas; IR-3, CIM-443, FH-1000, MNH-147, S-12 interacted undesirably with drought stress
A Line × Tester analysis for some seed cotton yield and fiber quality traits in upland cotton
Authors: Ullah Aziz , Shakeel Amir , Ahmed Hafiz Ghulam Muhu-Din , Ali Muhammad , Yar Muhammad Majid
Published: March 2021

The objective of the present study was to estimate general combining ability (GCA) of the parents and specific combining ability (SCA) of crosses for the development of high yielding cotton varieties. The study was carried out at the experimental area of Department of Plant Breeding and Genetics, University of Agriculture, Faisalabad. A line × tester analysis was made to identify the superior general and specific combiners for seed cotton yield and fiber quality traits in upland cotton. Five lines/females (FH-114, FH-1000, CIM-448, CIM-707, NIAB-111) and three testers/males (TH-41-83, Cocker-307 and Allepo-41) were crossed to develop 15 F1 hybrids. These genotypes were evaluated along with parents in RCBD with three replications. The general combining ability (GCA) and specific combining ability (SCA) mean squares for seed cotton yield, lint percentage, fiber fineness, fiber strength and fiber length were significant. The fiber fineness showed greater importance of additive gene effect while seed cotton yield, lint percentage, fiber strength and fiber length exhibited non additive genetic effects. Parents FH-114 and NIAB-111 among lines and COKER-307 from testers were found as good general combiners for most of the traits. Hence, these parents proved worth to be used in hybridization and selection program for extracting desirable plants from segregating population. F1 crosses CIM-707 × COKER-307, CIM-707 × ALLEPO-41 and FH-1000 × COKER-307, by and large, exhibited their superiority for all traits studied and were noted as the best specific combiners. Therefore, these crosses may be preferred to improve several traits simultaneously by selection or may be used for hybrid cotton crop development
GGE-Biplot analysis of multienvironments yield trials of Egyptian cotton (Gossypium barbadense L.,)
Authors: Abdelmoghny Ahmed Mohamed , Gibely Reham Helmy , Max Mariz Sobhy , Amer Emad Abdelazeim , Hassan Salah Saber
Published: March 2021

GGE biplot technique is one of the most appropriate methods for investigating the genotype x environment interaction. A total of twenty one Egyptian cotton genotypes were tested to evaluate stability and adaptability during two agricultural years at four environments using randomized complete block design with six replications. The analysis of variance showed that the effect of environments, years, environment x years, genotypes, and genotype x environment was highly significant for lint cotton yield / plot. Also, the interaction effect due to G x Y x E was also significant. The variation of sum of squares was divided for genotypes, years, environments, and GEI to 25.261 %, 0.574 %, 36.660 % and 3.396 % respectively of total variance for lint cotton yield / plot. The analysis of environments revealed that the cotton genotypes showed maximum mean values for lint cotton yield in El-Gharbiya then Kafr El-Sheikh. Comparative performance of genotypes through genotype by environment interaction (GEI) revealed that genotypes produced maximum lint cotton yield during 2019 at El-Gharbiya followed by Kafr El-Sheikh. The results of biplot analysis showed that the first and second principle components accounted 87.96 % and 5.86 %, respectively, and in total of 93.82 % lint cotton yield variance. The polygon view led to the identification of top six genotypes. G6, G7 and G15 were the ideal genotypes which has the highest mean performance coupled with maximum stability. The ideal genotype could be used as a benchmark for selection. While, the desirable genotypes was (G2, G4 and G5) characterized by high mean yield but less ideal genotypes. E2 was the ideal environment across four environments which have the highest ability to discriminate the genotypes. Four environments had long vectors with small angles (acute) are highly correlated and clustered as one mega-environment. The cotton breeder should evaluate the genotypes under new environments to reduce the costs.
Automated Online Flow Cytometry Advances Microalgal Ecosystem Management as in situ, High-Temporal Resolution Monitoring Tool
Authors: Haberkorn Iris , Off Cosima L. , Besmer Michael D. , Buchmann Leandro , Mathys Alexander
Published: March 2021

Microalgae are emerging as a next-generation biotechnological production system in the pharmaceutical, biofuel, and food domain. The economization of microalgal biorefineries remains a main target, where culture contamination and prokaryotic upsurge are main bottlenecks to impair culture stability, reproducibility, and consequently productivity. Automated online flow cytometry (FCM) is gaining momentum as bioprocess optimization tool, as it allows for spatial and temporal landscaping, real-time investigations of rapid microbial processes, and the assessment of intrinsic cell features. So far, automated online FCM has not been applied to microalgal ecosystems but poses a powerful technology for improving the feasibility of microalgal feedstock production through in situ, real-time, high-temporal resolution monitoring. The study lays the foundations for an application of automated online FCM implying far-reaching applications to impel and facilitate the implementation of innovations targeting at microalgal bioprocesses optimization. It shows that emissions collected on the FL1/FL3 fluorescent channels, harnessing nucleic acid staining and chlorophyll autofluorescence, enable a simultaneous assessment (quantitative and diversity-related) of prokaryotes and industrially relevant phototrophic Chlorella vulgaris in mixed ecosystems of different complexity over a broad concentration range (2.2–1,002.4 cells ⋅μL–1). Automated online FCM combined with data analysis relying on phenotypic fingerprinting poses a powerful tool for quantitative and diversity-related population dynamics monitoring. Quantitative data assessment showed that prokaryotic growth phases in engineered and natural ecosystems were characterized by different growth speeds and distinct peaks. Diversity-related population monitoring based on phenotypic fingerprinting indicated that prokaryotic upsurge in mixed cultures was governed by the dominance of single prokaryotic species. Automated online FCM is a powerful tool for microalgal bioprocess optimization owing to its adaptability to myriad phenotypic assays and its compatibility with various cultivation systems. This allows advancing bioprocesses associated with both microalgal biomass and compound production. Hence, automated online FCM poses a viable tool with applications across multiple domains within the biobased sector relying on single cell–based value chains.
On the Embryonic Development of the Nasal Turbinals and Their Homology in Bats
Authors: Ito Kai , Tu Vuong Tan , Eiting Thomas P. , Nojiri Taro , Koyabu Daisuke
Published: March 2021

Multiple corrugated cartilaginous structures are formed within the mammalian nasal capsule, eventually developing into turbinals. Due to its complex and derived morphology, the homologies of the bat nasal turbinals have been highly disputed and uncertain. Tracing prenatal development has been proven to provide a means to resolve homological problems. To elucidate bat turbinate homology, we conducted the most comprehensive study to date on prenatal development of the nasal capsule. Using diffusible iodine-based contrast-enhanced computed tomography (diceCT), we studied in detail the 3D prenatal development of various bat species and non-bat laurasiatherians. We found that the structure previously identified as “maxilloturbinal” is not the true maxilloturbinal and is only part of the ethmoturbinal I pars anterior. Our results also allowed us to trace the evolutionary history of the nasal turbinals in bats. The turbinate structures are overall comparable between laurasiatherians and pteropodids, suggesting that pteropodids retain the ancestral laurasiatherian condition. The absence of the ethmoturbinal I pars posterior in yangochiropterans and rhinolophoids has possibly occurred independently by convergent evolution.
Cell Metabolism and DNA Repair Pathways: Implications for Cancer Therapy
Authors: Sobanski Thais , Rose Maddison , Suraweera Amila , O’Byrne Kenneth , Richard Derek J. , Bolderson Emma
Published: March 2021

DNA repair and metabolic pathways are vital to maintain cellular homeostasis in normal human cells. Both of these pathways, however, undergo extensive changes during tumorigenesis, including modifications that promote rapid growth, genetic heterogeneity, and survival. While these two areas of research have remained relatively distinct, there is growing evidence that the pathways are interdependent and intrinsically linked. Therapeutic interventions that target metabolism or DNA repair systems have entered clinical practice in recent years, highlighting the potential of targeting these pathways in cancer. Further exploration of the links between metabolic and DNA repair pathways may open new therapeutic avenues in the future. Here, we discuss the dependence of DNA repair processes upon cellular metabolism; including the production of nucleotides required for repair, the necessity of metabolic pathways for the chromatin remodeling required for DNA repair, and the ways in which metabolism itself can induce and prevent DNA damage. We will also discuss the roles of metabolic proteins in DNA repair and, conversely, how DNA repair proteins can impact upon cell metabolism. Finally, we will discuss how further research may open therapeutic avenues in the treatment of cancer.
The Dual Role of STAT1 in Ovarian Cancer: Insight Into Molecular Mechanisms and Application Potentials
Authors: Li Xin , Wang Fanchen , Xu Xiaolin , Zhang Jinguo , Xu Guoxiong
Published: March 2021

The signal transducer and activator of transcription 1 (STAT1) is a transducer protein and acts as a transcription factor but its role in ovarian cancer (OC) is not completely understood. Practically, there are two-faced effects of STAT1 on tumorigenesis in different kinds of cancers. Existing evidence reveals that STAT1 has both tumor-suppressing and tumor-promoting functions involved in angiogenesis, cell proliferation, migration, invasion, apoptosis, drug resistance, stemness, and immune responses mainly through interacting and regulating target genes at multiple levels. The canonical STAT1 signaling pathway shows that STAT1 is phosphorylated and activated by the receptor-activated kinases such as Janus kinase in response to interferon stimulation. The STAT1 signaling can also be crosstalk with other signaling such as transforming growth factor-β signaling involved in cancer cell behavior. OC is often diagnosed at an advanced stage due to symptomless or atypical symptoms and the lack of effective detection at an early stage. Furthermore, patients with OC often develop chemoresistance and recurrence. This review focuses on the multi-faced role of STAT1 and highlights the molecular mechanisms and biological functions of STAT1 in OC.
Reconciling VEGF With VPF: The Importance of Increased Vascular Permeability for Stroma Formation in Tumors, Healing Wounds, and Chronic Inflammation
Authors: Dvorak Harold F.
Published: March 2021

It is widely believed that vascular endothelial growth factor (VEGF) induces angiogenesis by its direct mitogenic and motogenic actions on vascular endothelial cells. However, these activities are only detected when endothelial cells are cultured at very low (0.1%) serum concentrations and would not be expected to take place at the much higher serum levels found in angiogenic sitesin vivo. This conundrum can be resolved by recalling VEGF’s original function, that of an extremely potent vascular permeability factor (VPF).In vivoVPF/VEGF increases microvascular permeability such that whole plasma leaks into the tissues where it undergoes clotting by tissue factor that is expressed on tumor and host connective tissue cells to deposit fibrin and generate serum. By providing tissue support and by reprogramming the gene expression patterns of cells locally, fibrin and serum can together account for the formation of vascular connective tissue stroma. In sum, by increasing vascular permeability, VPF/VEGF triggers the “wound healing response,” setting in motion a fundamental pathophysiological process that induces the mature stroma that is found not only in healing wounds but also in solid tumors and chronic inflammatory diseases. Once initiated by increased vascular permeability, this response may be difficult to impede, perhaps contributing to the limited success of anti-VEGF therapies in treating cancer.
Black Boxes and the Role of Modeling in Environmental Policy Making
Authors: Maeda Eduardo Eiji , Haapasaari Päivi , Helle Inari , Lehikoinen Annukka , Voinov Alexey , Kuikka Sakari
Published: March 2021

Modeling is essential for modern science, and science-based policies are directly affected by the reliability of model outputs. Artificial intelligence has improved the accuracy and capability of model simulations, but often at the expense of a rational understanding of the systems involved. The lack of transparency in black box models, artificial intelligence based ones among them, can potentially affect the trust in science driven policy making. Here, we suggest that a broader discussion is needed to address the implications of black box approaches on the reliability of scientific advice used for policy making. We argue that participatory methods can bridge the gap between increasingly complex scientific methods and the people affected by their interpretations
Aberrantly DNA Methylated-Differentially Expressed Genes in Pancreatic Cancer Through an Integrated Bioinformatics Approach
Authors: Sun Haifeng , Xin Rui , Zheng Changjun , Huang Ge
Published: March 2021

Pancreatic cancer remains one of the chief contributors to cancer related deaths on a global scale, with its diagnosis often associated with poor prognosis and high mortality. Accumulating literature continues to highlight the role of aberrant DNA methylation in relation to pancreatic cancer progression. Integrated bioinformatics approaches in the characterization of methylated-differentially expressed genes (MeDEGs) in pancreatic cancer were employed to enhance our understanding of the potential underlying molecular mechanisms of this cancer. We initially identified differentially expressed genes (DEGs) between 178 pancreatic cancer samples and 4 normal samples and differentially methylated genes (DMGs) based on 185 pancreatic cancer samples as well as 10 normal samples by analyzing RNA sequencing data in the TCGA database. Eventually, 31 MeDEGs including 5 hypomethylated/upregulated genes and 26 hypermethylated/downregulated genes were identified. Univariate Cox model and Kaplan–Meier method revealed that, among 31 MeDEGs, 5 hypermethylated/downregulated genes (ZNF804A, ZFP82, TRIM58, SOX17, and C12orf42) were correlated with poor survival of patients with pancreatic cancer. KEGG pathway enrichment analysis by GSEA 3.0 and the protein–protein interaction (PPI) network revealed that these 5 MeDEGs were enriched in numerous cancer-related pathways in addition to interacting with each other, highlighting a significant role in the development of pancreatic cancer. Taken together, the key findings of the current study demonstrate that ZNF804A, ZFP82, TRIM58, SOX17, and C12orf42 are hypermethylated/downregulated genes in pancreatic cancer and may be associated, through their modulation of specific pathways, with unfavorable pancreatic cancer prognosis.
iEnhancer-EBLSTM: Identifying Enhancers and Strengths by Ensembles of Bidirectional Long Short-Term Memory
Authors: Niu Kun , Luo Ximei , Zhang Shumei , Teng Zhixia , Zhang Tianjiao , Zhao Yuming
Published: March 2021

Enhancers are regulatory DNA sequences that could be bound by specific proteins named transcription factors (TFs). The interactions between enhancers and TFs regulate specific genes by increasing the target gene expression. Therefore, enhancer identification and classification have been a critical issue in the enhancer field. Unfortunately, so far there has been a lack of suitable methods to identify enhancers. Previous research has mainly focused on the features of the enhancer’s function and interactions, which ignores the sequence information. As we know, the recurrent neural network (RNN) and long short-term memory (LSTM) models are currently the most common methods for processing time series data. LSTM is more suitable than RNN to address the DNA sequence. In this paper, we take the advantages of LSTM to build a method named iEnhancer-EBLSTM to identify enhancers. iEnhancer-ensembles of bidirectional LSTM (EBLSTM) consists of two steps. In the first step, we extract subsequences by sliding a 3-mer window along the DNA sequence as features. Second, EBLSTM model is used to identify enhancers from the candidate input sequences. We use the dataset from the study of Quang H et al. as the benchmarks. The experimental results from the datasets demonstrate the efficiency of our proposed model.
Bovine Coronavirus Immune Milk Against COVID-19
Authors: Arenas Antonio , Borge Carmen , Carbonero Alfonso , Garcia-Bocanegra Ignacio , Cano-Terriza David , Caballero Javier , Arenas-Montes Antonio
Published: March 2021

After a year of evolution of the SARS-CoV-2 epidemic, there is still no specific effective treatment for the disease. Although the majority of infected people experience mild disease, some patients develop a serious disease, especially when other pathologies concur. For this reason, it would be very convenient to find pharmacological and immunological mechanisms that help control SARS-CoV-2 infection. Since the COVID-19 and BCoV viruses are very close phylogenetically, different studies demonstrate the existence of cross-immunity as they retain shared epitopes in their structure. As a possible control measure against COVID-19, we propose the use of cow’s milk immune to BCoV. Thus, the antigenic recognition of some highly conserved structures of viral proteins, particularly M and S2, by anti-BCoV antibodies present in milk would cause a total or partial inactivation of SARS-COV-2 (acting as a particular vaccine) and be addressed more easily by GALT’s highly specialized antigen-presenting cells, thus helping the specific immune response.
Broad Purpose Vector for Site-Directed Insertional Mutagenesis in Bifidobacterium breve
Authors: Hoedt Emily C. , Bottacini Francesca , Cash Nora , Bongers Roger S. , van Limpt Kees , Ben Amor Kaouther , Knol Jan , MacSharry John , van Sinderen Douwe
Published: March 2021

Members of the genus Bifidobacterium are notoriously recalcitrant to genetic manipulation due to their extensive and variable repertoire of Restriction-Modification (R-M) systems. Non-replicating plasmids are currently employed to achieve insertional mutagenesis in Bifidobacterium. One of the limitations of using such insertion vectors is the presence within their sequence of various restriction sites, making them sensitive to the activity of endogenous restriction endonucleases encoded by the target strain. For this reason, vectors have been developed with the aim of methylating and protecting the vector using a methylase-positive Escherichia coli strain, in some cases containing a cloned bifidobacterial methylase. Here, we present a mutagenesis approach based on a modified and synthetically produced version of the suicide vector pORI28 (named pFREM28), where all known restriction sites targeted by Bifidobacterium breve R-M systems were removed by base substitution (thus preserving the codon usage). After validating the integrity of the erythromycin marker, the vector was successfully employed to target an α-galactosidase gene responsible for raffinose metabolism, an alcohol dehydrogenase gene responsible for mannitol utilization and a gene encoding a priming glycosyltransferase responsible for exopolysaccharides (EPS) production in B. breve. The advantage of using this modified approach is the reduction of the amount of time, effort and resources required to generate site-directed mutants in B. breve and a similar approach may be employed to target other (bifido)bacterial species.
A Novel Grape-Derived Prebiotic Selectively Enhances Abundance and Metabolic Activity of Butyrate-Producing Bacteria in Faecal Samples
Authors: Oliver Lia , Ramió-Pujol Sara , Amoedo Joan , Malagón Marta , Serrano Marta , Bahí Anna , Lluansí Aleix , Torrealba Leyanira , Busquets David , Pardo Laura , Serra-Pagès Mariona , Aldeguer Xavier , Garcia-Gil Jesús
Published: March 2021

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) patients have different faecal microbiota profiles compared to healthy controls. Prebiotics intake influences intestinal microbiota composition which in turn influence the growth of short-chain fatty acids (SCFA) producing bacteria. This study aimed to evaluate the capacity of Previpect, a new prebiotic obtained from grapes fibre, to balance the dysbiosis found in patients with intestinal disorders. This was achieved through the analysis of specific bacterial markers and SCFA production using an in vitro fermentation system and comparing the obtained results with those obtained with other commercial prebiotics. Fresh faecal samples from patients with IBD (N = 6), IBS (N = 3), and control subjects (N = 6) were used. Previpect showed high fermentative ability enabling the growth of butyrate producing bacteria and increasing SCFA concentration up to 2.5-fold. Previpect is a promising prebiotic which may be used as a therapeutic strategy towards promotion of intestinal microbiota restoration, microbial healing, and as a preventive supplement for healthy individuals.
Substrate Inhibition of 5β-Δ4-3-Ketosteroid Dehydrogenase in Sphingobium sp. Strain Chol11 Acts as Circuit Breaker During Growth With Toxic Bile Salts
Authors: Feller Franziska M. , Marke Gina , Drees Steffen L. , Wöhlbrand Lars , Rabus Ralf , Philipp Bodo
Published: March 2021

In contrast to many steroid hormones and cholesterol, mammalian bile salts are 5β-steroids, which leads to a bent structure of the steroid core. Bile salts are surface-active steroids excreted into the environment in large amounts, where they are subject to bacterial degradation. Bacterial steroid degradation is initiated by the oxidation of the A-ring leading to canonical Δ4-3-keto steroids with a double bond in the A-ring. For 5β-bile salts, this Δ4-double bond is introduced into 3-keto-bile salts by a 5β-Δ4-ketosteroid dehydrogenase (5β-Δ4-KSTD). With the Nov2c019 protein from bile-salt degradingSphingobiumsp. strain Chol11, a novel 5β-Δ4-KSTD for bile-salt degradation belonging to the Old Yellow Enzyme family was identified and named 5β-Δ4-KSTD1. By heterologous production inEscherichia coli, 5β-Δ4-KSTD function could be shown for 5β-Δ4-KSTD1 as well as the homolog CasH from bile-salt degradingRhodococcus jostiiRHA1. The deletion mutant of5β-Δ4-kstd1had a prolonged lag-phase with cholate as sole carbon source and, in accordance with the function of 5β-Δ4-KSTD1, showed delayed 3-ketocholate transformation. Purified 5β-Δ4-KSTD1 was specific for 5β-steroids in contrast to 5α-steroids and converted steroids with a variety of hydroxy groups regardless of the presence of a side chain. 5β-Δ4-KSTD1 showed a relatively lowKmfor 3-ketocholate, a very high specific activity and pronounced substrate inhibition. With respect to the toxicity of bile salts, these kinetic properties indicate that 5β-Δ4-KSTD1 can achieve fast detoxification of the detergent character as well as prevention of an overflow of the catabolic pathway in presence of increased bile-salt concentrations.
Biomarkers and the Role of α-Synuclein in Parkinson’s Disease
Authors: Du Tingting , Wang Le , Liu Weijin , Zhu Guanyu , Chen Yingchuan , Zhang Jianguo
Published: March 2021

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the presence of α-synuclein (α-Syn)-rich Lewy bodies (LBs) and the preferential loss of dopaminergic (DA) neurons in the substantia nigra (SN) pars compacta (SNpc). However, the widespread involvement of other central nervous systems (CNS) structures and peripheral tissues is now widely documented. The onset of the molecular and cellular neuropathology of PD likely occurs decades before the onset of the motor symptoms characteristic of PD, so early diagnosis of PD and adequate tracking of disease progression could significantly improve outcomes for patients. Because the clinical diagnosis of PD is challenging, misdiagnosis is common, which highlights the need for disease-specific and early-stage biomarkers. This review article aims to summarize useful biomarkers for the diagnosis of PD, as well as the biomarkers used to monitor disease progression. This review article describes the role of α-Syn in PD and how it could potentially be used as a biomarker for PD. Also, preclinical and clinical investigations encompassing genetics, immunology, fluid and tissue, imaging, as well as neurophysiology biomarkers are discussed. Knowledge of the novel biomarkers for preclinical detection and clinical evaluation will contribute to a deeper understanding of the disease mechanism, which should more effectively guide clinical applications.
Neurologic and Neuroscientific Evidence in Aged COVID-19 Patients
Authors: Mainali Shraddha , Darsie Marin E.
Published: March 2021

The COVID-19 pandemic continues to prevail as a catastrophic wave infecting over 111 million people globally, claiming 2. 4 million lives to date. Aged individuals are particularly vulnerable to this disease due to their fraility, immune dysfunction, and higher rates of medical comorbidities, among other causes. Apart from the primary respiratory illness, this virus is known to cause multi-organ dysfunction including renal, cardiac, and neurologic injuries, particularly in the critically-ill cohorts. Elderly patients 65 years of age or older are known to have more severe systemic disease and higher rates of neurologic complications. Morbidity and mortality is very high in the elderly population with 6–930 times higher likelihood of death compared to younger cohorts, with the highest risk in elderly patients ≥85 years and especially those with medical comorbidities such as hypertension, diabetes, heart disease, and underlying respiratory illness. Commonly reported neurologic dysfunctions of COVID-19 include headache, fatigue, dizziness, and confusion. Elderly patients may manifest atypical presentations like fall or postural instability. Other important neurologic dysfunctions in the elderly include cerebrovascular diseases, cognitive impairment, and neuropsychiatric illnesses. Elderly patients with preexisting neurologic diseases are susceptibility to severe COVID-19 infection and higher rates of mortality. Treatment of neurologic dysfunction of COVID-19 is based on existing practice standards of specific neurologic condition in conjunction with systemic treatment of the viral illness. The physical, emotional, psychologic, and financial implications of COVID-19 pandemic have been severe. Long-term data are still needed to understand the lasting effects of this devastating pandemic.
Hypothesis and Theory: Roles of Arginine Methylation in C9orf72-Mediated ALS and FTD
Authors: Gill Anna L. , Premasiri Alan S. , Vieira Fernando G.
Published: March 2021

Hexanucleotide repeat expansion (G4C2n) mutations in the gene C9ORF72 account for approximately 30% of familial cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), as well as approximately 7% of sporadic cases of ALS. G4C2n mutations are known to result in the production of five species of dipeptide repeat proteins (DRPs) through non-canonical translation processes. Arginine-enriched dipeptide repeat proteins, glycine-arginine (polyGR), and proline-arginine (polyPR) have been demonstrated to be cytotoxic and deleterious in multiple experimental systems. Recently, we and others have implicated methylation of polyGR/polyPR arginine residues in disease processes related to G4C2n mutation-mediated neurodegeneration. We previously reported that inhibition of asymmetric dimethylation (ADMe) of arginine residues is protective in cell-based models of polyGR/polyPR cytotoxicity. These results are consistent with the idea that PRMT-mediated arginine methylation in the context of polyGR/polyPR exposure is harmful. However, it remains unclear why. Here we discuss the influence of arginine methylation on diverse cellular processes including liquid-liquid phase separation, chromatin remodeling, transcription, RNA processing, and RNA-binding protein localization, and we consider how methylation of polyGR/polyPR may disrupt processes essential for normal cellular function and survival.
The Involvement of CaV1.3 Channels in Prolonged Root Reflexes and Its Potential as a Therapeutic Target in Spinal Cord Injury
Authors: Jiang Mingchen C. , Birch Derin V. , Heckman Charles J. , Tysseling Vicki M.
Published: March 2021

Spinal cord injury (SCI) results in not only the loss of voluntary muscle control, but also in the presence of involuntary movement or spasms. These spasms post-SCI involve hyperexcitability in the spinal motor system. Hyperactive motor commands post SCI result from enhanced excitatory postsynaptic potentials (EPSPs) and persistent inward currents in voltage-gated L-type calcium channels (LTCCs), which are reflected in evoked root reflexes with different timings. To further understand the contributions of these cellular mechanisms and to explore the involvement of LTCC subtypes in SCI-induced hyperexcitability, we measured root reflexes with ventral root recordings and motoneuron activities with intracellular recordings in an in vitro preparation using a mouse model of chronic SCI (cSCI). Specifically, we explored the effects of 1-(3-chlorophenethyl)-3-cyclopentylpyrimidine-2,4,6-(1H,3H,5H)-trione (CPT), a selective negative allosteric modulator of CaV1.3 LTCCs. Our results suggest a hyperexcitability in the spinal motor system in these SCI mice. Bath application of CPT displayed slow onset but dose-dependent inhibition of the root reflexes with the strongest effect on LLRs. However, the inhibitory effect of CPT is less potent in cSCI mice than in acute SCI (aSCI) mice, suggesting changes either in composition of CaV1.3 or other cellular mechanisms in cSCI mice. For intracellular recordings, the intrinsic plateau potentials, was observed in more motoneurons in cSCI mice than in aSCI mice. CPT inhibited the plateau potentials and reduced motoneuron firings evoked by intracellular current injection. These results suggest that the LLR is an important target and that CPT has potential in the therapy of SCI-induced muscle spasms.
Evidence of Age-Related Hemodynamic and Functional Connectivity Impairment: A Resting State fMRI Study
Authors: Kavroulakis Eleftherios , Simos Nicholas J. , Maris Thomas G. , Zaganas Ioannis , Panagiotakis Simeon , Papadaki Efrosini
Published: March 2021

Purpose: To assess age-related changes in intrinsic functional brain connectivity and hemodynamics during adulthood in the context of the retrogenesis hypothesis, which states that the rate of age-related changes is higher in late-myelinating (prefrontal, lateral-posterior temporal) cerebrocortical areas as compared to early myelinating (parietal, occipital) regions. In addition, to examine the dependence of age-related changes upon concurrent subclinical depression symptoms which are common even in healthy aging.

Methods: Sixty-four healthy adults (28 men) aged 23–79 years (mean 45.0, SD = 18.8 years) were examined. Resting-state functional MRI (rs-fMRI) time series were used to compute voxel-wise intrinsic connectivity contrast (ICC) maps reflecting the strength of functional connectivity between each voxel and the rest of the brain. We further used Time Shift Analysis (TSA) to estimate voxel-wise hemodynamic lead or lag for each of 22 ROIs from the automated anatomical atlas (AAL).

Results: Adjusted for depression symptoms, gender and education level, reduced ICC with age was found primarily in frontal, temporal regions, and putamen, whereas the opposite trend was noted in inferior occipital cortices (p < 0.002). With the same covariates, increased hemodynamic lead with advancing age was found in superior frontal cortex and thalamus, with the opposite trend in inferior occipital cortex (p < 0.002). There was also evidence of reduced coupling between voxel-wise intrinsic connectivity and hemodynamics in the inferior parietal cortex.

Conclusion: Age-related intrinsic connectivity reductions and hemodynamic changes were demonstrated in several regions—most of them part of DMN and salience networks—while impaired neurovascular coupling was, also, found in parietal regions. Age-related reductions in intrinsic connectivity were greater in anterior as compared to posterior cortices, in line with implications derived from the retrogenesis hypothesis. These effects were affected by self-reported depression symptoms, which also increased with age.
Heart Rate Variability Analysis in Episodic Migraine: A Cross-Sectional Study
Authors: Zhang Lvming , Qiu Shi , Zhao Chunxia , Wang Peifu , Yu Shengyuan
Published: March 2021

Objective: It has been reported that autonomic nervous dysfunction is more prevalent in migraineurs. Heart rate variability (HRV) is a commonly used method to evaluate the cardiac autonomic nervous function modulation. However, HRV changes in migraine are still contradictory. The main objective of this study was to explore the potential HRV change patterns in episodic migraine (EM) and whether there were differences in HRV between EM ictal period and the interictal period.

Patients and Methods: We conducted a cross-sectional study including 18 patients with EM and 18 age- and sex-matched controls. The characteristics of demographics, some lifestyle factors, and psychological conditions were assessed at baseline. HRVs including time-domain analysis and frequency-domain analysis were performed in all participants. HRV analyses in migraine were recorded not only in the interictal period but also in the ictal period.

Results: All the HRV parameters showed a decreased trend in migraine than controls. Time-domain parameters standard deviation of all NN intervals in 24 h (SDNN) and triangular index were significantly lower in the migraine ictal period than controls separately (SDNN, 56.94 ± 22.09 ± 7.76 vs. 135.78 ± 35.16, p < 0.001; triangular index, 12.61 ± 3.20 vs. 22.11 ± 6.90, p < 0.001). Frequency-domain parameter low-frequency power was also lower in the migraine ictal period than controls (351.28 ± 206.71 vs. 559.61 ± 281.24, p = 0.02). SDNN was much lower in the migraine ictal period than migraine interictal period (56.94 ± 22.09 vs. 115.94 ± 46.88, p < 0.001). HRV changes during migraine interictal period did not differ from the control group. The correlation analysis revealed a negative correlation between visual analog scale and HRV parameters in the migraine ictal period (p = 0.04).

Conclusions: The present cross-sectional study indicates that HRV was significantly decreased in EM population especially during the migraine ictal period, which means unbalance of autonomic system in EM. Perhaps larger prospective cohort studies are wanted to validate these findings.
Morphological Changes in Cortical and Subcortical Structures in Multiple System Atrophy Patients With Mild Cognitive Impairment
Authors: Cao Chenghao , Wang Qi , Yu Hongmei , Yang Huaguang , Li Yingmei , Guo Miaoran , Huo Huaibi , Fan Guoguang
Published: March 2021

Objective

This study aimed to investigate the morphometric alterations in the cortical and subcortical structures in multiple system atrophy (MSA) patients with mild cognitive impairment (MCI), and to explore the association with cognitive deficits.

Methods

A total of 45 MSA patients (25 MSA-only, 20 MSA-MCI) and 29 healthy controls were recruited. FreeSurfer software was used to analyze cortical thickness, and voxel-based morphometry was used to analyze the gray matter volumes. Cortical thickness and gray matter volume changes were correlated with cognitive scores.

Results

Compared to healthy controls, both MSA subgroups exhibited widespread morphology alterations of brain structures in the fronto-temporal regions. Direct comparison of MSA-MCI and MSA-only patients showed volume reduction in the left superior and middle temporal gyrus, while cortical thinning was found in the left middle and inferior temporal gyrus in MSA-MCI patients. Cortical thinning in the left middle temporal gyrus correlated with cognitive assessment and disease duration.

Conclusion

Structural changes in the brain occur in MSA-MCI patients. The alteration of brain structure in the left temporal regions might be a biomarker of cognitive decline in MSA-MCI patients.
New Insight of Circular RNAs' Roles in Central Nervous System Post-Traumatic Injury
Authors: Xu Lvwan , Ye Xin , Zhong Jinjie , Chen Ying-ying , Wang Lin-lin
Published: March 2021

The central nervous system (CNS) post-traumatic injury can cause severe nerve damage with devastating consequences. However, its pathophysiological mechanisms remain vague. There is still an urgent need for more effective treatments. Circular RNAs (circRNAs) are non-coding RNAs that can form covalently closed RNA circles. Through second-generation sequencing technology, microarray analysis, bioinformatics, and other technologies, recent studies have shown that a number of circRNAs are differentially expressed after traumatic brain injury (TBI) or spinal cord injury (SCI). These circRNAs play important roles in the proliferation, inflammation, and apoptosis in CNS post-traumatic injury. In this review, we summarize the expression and functions of circRNAs in CNS in recent studies, as well as the circRNA–miRNA–mRNA interaction networks. The potential clinical value of circRNAs as a therapeutic target is also discussed.
Genesis of the Master Circadian Pacemaker in Mice
Authors: Cheng Arthur H. , Cheng Hai-Ying Mary
Published: March 2021

The suprachiasmatic nucleus (SCN) of the hypothalamus is the central circadian clock of mammals. It is responsible for communicating temporal information to peripheral oscillators via humoral and endocrine signaling, ultimately controlling overt rhythms such as sleep-wake cycles, body temperature, and locomotor activity. Given the heterogeneity and complexity of the SCN, its genesis is tightly regulated by countless intrinsic and extrinsic factors. Here, we provide a brief overview of the development of the SCN, with special emphasis on the murine system.