bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on the Calculation Method of Equivalent Parameters of the Core Wire for the High-Voltage GIL Metal Shell Grounded Through the Copper Bar
Authors: Li Botong , Shi Lin , Wen Weijie , Li Bin , Gu Tianfeng
Published: March 2022

The calculation method of the equivalent impedance and admittance parameters of the Gas Insulated Line (the Gas Insulated Line is abbreviated as GIL in this paper) grounded by the copper bar is studied and proposed. In consideration of the electrical coupling among the metal shell, the core wire, and the grounding copper bar, the matrix forms and characteristics of GIL impedance and admittance parameters are analyzed. The method of eliminating the coupling among the conductor layers, the grounding copper bar, and the core wire is studied in accordance with the current and voltage boundary conditions. Eventually, the calculation method of equivalent impedance and admittance parameters of the GIL core wire is proposed. The correctness of the calculation method of GIL core wire equivalent parameters is verified by simulation comparisons in PSCAD. This method can obtain the equivalent parameters of the GIL core wire by eliminating the coupling effect of external conductors and simplifies the seventh-order parameter matrix of the multi-layer GIL line to a third-order matrix that only considers the core wire parameters. The calculation speed can be significantly improved for short-circuit current calculation and related analysis of high-voltage AC systems containing GIL by using the equivalent parameters.
Spatial and Temporal Global Patterns of Drought Propagation
Authors: Fuentes Ignacio , Padarian José , Vervoort R. Willem
Published: March 2022

Drought is the most expensive natural hazard and one of the deadliest. While drought propagation through standardised indices has been extensively studied at the regional scale, global scale drought propagation, and particularly quantifying the space and time variability, is still a challenging task. Quantifying the space time variability is crucial to understand how droughts have changed globally in order to cope with their impacts. In particular, better understanding of the propagation of drought through the climate, vegetation and hydrological subsystems can improve decision making and preparedness. This study maps spatial temporal drought propagation through different subsystems at the global scale over the last decades. The standardised precipitation index (SPI) based on the gamma distribution, the standardised precipitation evapotranspiration index (SPEI) based on the log-logistic distribution, the standardised vegetation index (SVI) based on z-scores, and the standardised runoff index (SRI) based on empirical runoff probabilities were quantified. Additionally, drought characteristics, including duration, severity and intensity were estimated. Propagation combined the delay in response in the subsystems using drought characteristics, and trends in time were analysed. All these were calculated at 0.05 to 0.25 arc degree pixels. In general, drought propagates rapidly to the response in runoff and streamflow, and a with longer delay in the vegetation. However, this response varies spatially across the globe and depending on the observation scale, and amplifies progressively in duration and severity across large regions from the meteorological to the agricultural/ecological and hydrologic subsystems, while attenuating in intensity. Significant differences exist between major Köppen climate groups in drought characteristics and propagation. Patterns show intensification of drought severity and propagation affecting vegetation and hydrology in regions of southern South America, Australia, and South West Africa.
Biocrusts Influence Vascular Plant Community Development, Promoting Native Plant Dominance
Authors: Bowker Matthew A. , Doherty Kyle D. , Antoninka Anita J. , Ramsey Philip W. , DuPre Mary Ellyn , Durham Rebecca A.
Published: March 2022

The soil and its biota can shape the development of colonizing vascular plant communities. Because they occupy soil surfaces where most seeds disperse to, biological soil crusts (biocrusts) are uniquely positioned to influence vascular plant communities established by direct seeding, e.g., for restoration. We created mesocosms of soil overtopped by intact biocrust transplants from the field, varying in key community attributes: total cover, species richness, and proportional cover of mosses relative to lichens. We seeded the same diverse mixture of vascular plants into all mesocosms, including desired native species and problematic exotic invasive species. We tracked plant community development for two full growing seasons, both under ambient outdoor conditions and with supplemental irrigation to remove the influence of water limitation. Under ambient conditions, we found that total biocrust cover suppressed exotic plant emergence and biocrust richness slightly promoted native emergence (r = −0.23 to −0.39) but had weaker and less consistent effects on cover of either native or exotic plants (r ≤ |0.25|). Early emergence events were generally strong drivers of vascular plant recruitment (r = 0.17–0.78) and continued to influence community composition after 2 years, suggesting a priority effect. Biocrust cover also promoted final plant biomass under ambient conditions (r = 0.17–0.33) but did not influence the total cumulative number of native species (r ≤ |0.07|) nor the fecundity of exotics (r ≤ |0.08|). Biocrusts’ influence on total vascular plant biomass was minor. When water was added, biocrust effects sometimes switched from positive or negative to neutral, or vice-versa, indicating that our detection probability of biocrust effects on plants changes with moisture availability. Our results demonstrate that the condition of pre-existing biocrust communities can influence—but not strongly dictate—the outcome of multi-species restoration seedings, mostly positively or neutrally under normal conditions, but switching to potentially negatively under irrigated conditions. Our study also suggests that locations with more intact and richer biocrust communities might be slightly more conducive to successful seeding outcomes, while also providing additional contributions to ecosystem functions. As such, biocrusts, alongside vascular plants, have a role in restoring damaged or degraded ecosystems.
Epigenetic Clock Deceleration and Maternal Reproductive Efforts: Associations With Increasing Gray Matter Volume of the Precuneus
Authors: Nishitani Shota , Kasaba Ryoko , Hiraoka Daiki , Shimada Koji , Fujisawa Takashi X. , Okazawa Hidehiko , Tomoda Akemi
Published: March 2022

Reproductive efforts, such as pregnancy, delivery, and interaction with children, make maternal brains optimized for child-rearing. However, extensive studies in non-human species revealed a tradeoff between reproductive effort and life expectancy. In humans, large demographic studies have shown that this is the case for the most part; however, molecular marker studies regarding aging remain controversial. There are no studies simultaneously evaluating the relationship between reproductive effort, aging, and brain structures. We therefore examined the associations between reproductive efforts (parity status, number of deliveries, motherhood period, and cumulative motherhood period), DNA methylation age (mAge) acceleration (based on Horvath’s multi-tissue clock and the skin & blood clock), and the regional gray matter volumes (obtained through brain magnetic resonance imaging (MRI) using voxel-based morphometry) in 51 mothers aged 27–46 years of children in early childhood. We found that increasing reproductive efforts were significantly associated with decelerated aging in mothers with one to four children, even after adjusting for the confounding effects in the multiple linear regression models. We also found that the left precuneus gray matter volume was larger as deceleration of aging occurred; increasing left precuneus gray matter volume, on the other hand, mediates the relationship between parity status and mAge deceleration. Our findings suggest that mothers of children in early childhood, who have had less than four children, may benefit from deceleration of aging mediated via structural changes in the precuneus.
Reduced T Cell and Antibody Responses to Inactivated Coronavirus Vaccine Among Individuals Above 55 Years Old
Authors: Medeiros Giuliana X. , Sasahara Greyce Luri , Magawa Jhosiene Y. , Nunes João Paulo S. , Bruno Fernanda R. , Kuramoto Andreia C. , Almeida Rafael R. , Ferreira Marcelo A. , Scagion Guilherme P. , Candido Érika D. , Leal Fabyano B. , Oliveira Danielle B. L. , Durigon Edison L. , Silva Roberto Carlos V. , Rosa Daniela S. , Boscardin Silvia B. , Coelho Verônica , Kalil Jorge , Santos Keity S. , Cunha-Neto Edecio
Published: March 2022

CoronaVac is an inactivated SARS-CoV-2 vaccine that has been rolled out in several low and middle-income countries including Brazil, where it was the mainstay of the first wave of immunization of healthcare workers and the elderly population. We aimed to assess the T cell and antibody responses of vaccinated individuals as compared to convalescent patients. We detected IgG against SARS-CoV-2 antigens, neutralizing antibodies against the reference Wuhan SARS-CoV-2 strain and used SARS-CoV-2 peptides to detect IFN-g and IL-2 specific T cell responses in a group of CoronaVac vaccinated individuals (N = 101) and convalescent (N = 72) individuals. The frequency among vaccinated individuals, of whom 96% displayed T cell and/or antibody responses to SARS-CoV-2, is comparable to 98.5% responses of convalescent individuals. We observed that among vaccinated individuals, men and individuals 55 years or older developed significantly lower anti-RBD, anti-NP and neutralization titers against the Wuhan strain and antigen-induced IL-2 production by T cells. Neutralizing antibody responses for Gamma variant were even lower than for the Wuhan strain. Even though some studies indicated CoronaVac helped reduce mortality among elderly people, considering the appearance of novel variants of concern, CoronaVac vaccinated individuals above 55 years old are likely to benefit from a heterologous third dose/booster vaccine to increase immune response and likely protection.
Establishment of a 3-Dimensional Intestinal Cell Model to Simulate the Intestinal Mucosal Immune System for Food Allergy Investigations
Authors: Fu Linglin , Lin Wanglei , Wang Chong , Wang Yanbo
Published: March 2022

Food allergy is a worldwide food safety problem with increasing prevalence. Developing novel approaches for food allergy investigations is the basis for controlling food allergies. In this work, a 3-dimensional (3D) intestinal cell model was established to simulate the intestinal mucosal immune system. Gut epithelial cell line CMT93 was cultured in a transwell insert above dendritic cells (DCs) isolated from mouse spleen and stimulated by egg allergen ovalbumin (OVA), then the conditioned media of DCs was transferred to T cells isolated from mouse spleen. The allergy-related indexes of each cell type were determined by qPCR and flow cytometry. Then the TAZ gene was knocked down in the CMT93 cells and the role of the Hippo pathway in OVA-induced food allergy was investigated. The 3D intestinal cell model showed more significant and more specific allergic responses than conventional cell models and is more convenient to be manipulated than the mouse models. This model is an ideal tool for food allergy investigations and would facilitate studies in the field of intestinal mucosal immunity.
CpG Single-Site Methylation Regulates TLR2 Expression in Proinflammatory PBMCs From Apical Periodontitis Individuals
Authors: Bordagaray María José , Fernández Alejandra , Astorga Jessica , Garrido Mauricio , Hernández Patricia , Chaparro Alejandra , Lira María Jesús , Gebicke-Haerter Peter , Hernández Marcela
Published: March 2022

Introduction

Apical periodontitis (AP) is a common oral disease caused by the inflammatory destruction of the periapical tissues due to the infection of the root canal system of the tooth. It also contributes to systemic bacterial translocation, where peripheric mononuclear blood cells (PBMCs) can act as carriers. Toll-like receptor (TLR) 2 mediates the response to infection and activates inflammatory responses. DNA methylation can be induced by bacteria and contributes to the modulation of this response. Despite the evidence that supports the participation of PBMCs in immune-inflammatory disorders, the inflammatory profile and epigenetic regulatory mechanisms of PBMCs in AP individuals are unknown.

Aim

To determine TLR2 gene methylation and inflammatory profiles of PBMCs in AP.

Methods

Cross-sectional exploratory study. Otherwise, healthy individuals with AP (n=27) and controls (n=30) were included. PMBCs were isolated by a Ficoll gradient, cultured for 24 hours, and both RNA and DNA were extracted. DNA was bisulfite-treated, and specific sites at the promoter region of the TLR2 gene were amplified by qPCR using validated primers. To verify its amplification, agarose gels were performed. Then, the PCR product was sequenced. mRNA expression of TLR2 was determined by qPCR. The soluble levels of 105 inflammatory mediators were first explored with Proteome Profiler Human Cytokine Array Kit. Consequently, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, IL-6Rα, IL-1β, and IL-12p70 levels were measured by Multiplex assay.

Results

PBMCs from individuals with AP demonstrated a proinflammatory profile showing higher soluble levels of TNF-α, IL-6, and IL-1β compared to controls (p<0.05). Higher TLR2 expression and higher global methylation pattern of the promoter region of the gene were found in AP compared to controls (p<0.05). The CpGs single-sites at positions -166 and -146 were completely methylated, while the site -102 was totally unmethylated, independently of the presence of AP. DNA methylation of CpG single-sites in positions -77 and +24 was positively associated with TLR2 expression.

Conclusions

PBMCs from AP subjects show a hyperinflammatory phenotype and TLR2 upregulation in association with single CpG-sites’ methylation from the TLR2 gene promoter, thereby contributing to a sustained systemic inflammatory load in individuals with periapical endodontic diseases.
Target Product Profiles for Mosquito Gene Drives: Incorporating Insights From Mathematical Models
Authors: Mondal Agastya , Vásquez Váleri N. , Marshall John M.
Published: March 2022

Mosquito-borne diseases such as malaria continue to pose a major global health burden, and the impact of currently-available interventions is stagnating. Consequently, there is interest in novel tools to control these diseases, including gene drive-modified mosquitoes. As these tools continue to be refined, decisions on whether to implement them in the field depend on their alignment with target product profiles (TPPs) that define product characteristics required to achieve desired entomological and epidemiological outcomes. TPPs are increasingly being used for malaria and vector control interventions, such as attractive targeted sugar baits and long-acting injectable drugs, as they progress through the development pipeline. For mosquito gene drive products, reliable predictions from mathematical models are an essential part of these analyses, as field releases could potentially be irreversible. Here, we review the prior use of mathematical models in developing TPPs for malaria and vector control tools and discuss lessons from these analyses that may apply to mosquito gene drives. We recommend that, as gene drive technology gets closer to field release, discussions regarding target outcomes engage a wide range of stakeholders and account for settings of interest and vector species present. Given the relatively large number of parameters that describe gene drive products, machine learning approaches may be useful to explore parameter space, and an emphasis on conservative fitness estimates is advisable, given the difficulty of accurately measuring these parameters prior to field studies. Modeling may also help to inform the risk, remediation and cost dimensions of mosquito gene drive TPPs.
Discovery of 194 Unreported Conopeptides and Identification of a New Protein Disulfide Isomerase in Conus caracteristicus Using Integrated Transcriptomic and Proteomic Analysis
Authors: Zhang Han , Wang Lei , Qiu Yinbin , Gong Fahui , Nong Baoting , Pan Xinghua
Published: March 2022

Current ConoServer database accumulates 8,134 conopeptides from 122 species of cone snail, which are pharmaceutically attractive marine resource. However, many more conopeptides remain to be discovered, and the enzymes involved in their synthesis and processing are unclear. In this report, firstly we screened and analyzed the differentially expressed genes (DEGs) between venom duct (VD) and venom bulb (VB) of C. caracteristicus, and obtained 3,289 transcripts using a comprehensive assembly strategy. Then using de novo deep transcriptome sequencing and analysis under a strict merit, we discovered 194 previously unreported conopeptide precursors in Conus caracteristicus. Meanwhile, 2 predicted conopeptides from Consort were verified using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Furthermore, we demonstrated that both VD and VB of C. caracteristicus secreted hundreds of different conotoxins, which showed a high diversity among individuals of the species. Finally, we identified a protein disulfide isomerase (PDI) gene, which, functioning for intramolecular disulfide-bond folding, was shared among C. caracteristicus, C. textile, and C. bartschi and was the first PDI identified with five thioredoxin domains. Our results provide novel insights and fuel further studies of the molecular evolution and function of the novel conotoxins.
Rent Generation Under the Norwegian Rights-Based Pelagic Fishery
Authors: Bertheussen Bernt A. , Vassdal Terje
Published: March 2022

As a general rule, only active fishermen can own fishing boats for commercial fishing in Norway. Thus, vertical integration is not allowed. Accordingly, the Norwegian empirical context is exceptionally well suited to study actual rent creation as a potential resource rent can only accrue to the catch stage of the value chain. This paper examines profitability and rent generation of 35 seagoing Norwegian purse seiners (around half the population) for 13 consecutive years. The study period starts in 2005, which saw the introduction of the latest version of the Norwegian individual transferable quota (ITQ) variant, or the so-called structural quota (SQ) system. First, this study investigates how profitable a purse seiner has become during the SQ regime. As per our findings, it was found that the average annual return on equity (ROE) was 20.8% and that the book value of equity more than doubled over the period (a 166% increase). Moreover, for the cohort of 35 vessels, rent operationalized as residual income (RI) was reported for every year examined (2006–2017). The discounted value of RI for the period was approximately 50 million NOK per vessel, which is equivalent to about 5 million EUR. This implies that the players generated substantial rent. The findings of this study draw a picture of a financially stable and lucrative industry. Finally, implications of the findings are discussed.
Portuguese European Multidisciplinary Seafloor and Water Column Observatory Initiative
Authors: Carapuço Mafalda Marques , Silveira Tanya Mendes , Stroynowski Zuzia , Miranda Jorge Miguel
Published: March 2022

The Atlantic dimension of Portugal, with c. 1,700,000 km2 maritime area, led to the prioritization of the European Multidisciplinary Seafloor and water column Observatory - Portugal (EMSO-PT) in the national scientific infrastructures’ roadmap. In this work we present the EMSO-PT initiative: a research consortium joining 15 research institutions, with the aim of implementing a network of multidisciplinary underwater observatories in the Atlantic, as well as laboratories and data processing support infrastructures. EMSO-PT’s priority is to generate continuous scientific data on marine environmental processes related to the interaction between the geosphere, biosphere, and hydrosphere, and to develop new sensors and platforms which will extend ocean monitoring in the near future. Monitoring variables will include biotic and abiotic variables of the ocean floor and water column, namely temperature, salinity, turbidity, acoustics, currents, and dissolved oxygen. Data will be disseminated through European Multidisciplinary Seafloor and Water Column Observatory – European Research Infrastructure Consortiums (EMSO-ERIC) channels, allowing for the integration and open access of data acquired by all partners of EMSO-ERIC, and by the research community at large.
Emerging Roles of Aldehyde Dehydrogenase Isoforms in Anti-cancer Therapy Resistance
Authors: Zanoni Michele , Bravaccini Sara , Fabbri Francesco , Arienti Chiara
Published: March 2022

Aldehyde dehydrogenases (ALDHs) are a family of detoxifying enzymes often upregulated in cancer cells and associated with therapeutic resistance. In humans, the ALDH family comprises 19 isoenzymes active in the majority of mammalian tissues. Each ALDH isoform has a specific differential expression pattern and most of them have individual functional roles in cancer. ALDHs are overexpressed in subpopulations of cancer cells with stem-like features, where they are involved in several processes including cellular proliferation, differentiation, detoxification and survival, participating in lipids and amino acid metabolism and retinoic acid synthesis. In particular, ALDH enzymes protect cancer cells by metabolizing toxic aldehydes in less reactive and more soluble carboxylic acids. High metabolic activity as well as conventional anticancer therapies contribute to aldehyde accumulation, leading to DNA double strand breaks (DSB) through the generation of reactive oxygen species (ROS) and lipid peroxidation. ALDH overexpression is crucial not only for the survival of cancer stem cells but can also affect immune cells of the tumour microenvironment (TME). The reduction of ROS amount and the increase in retinoic acid signaling impairs immunogenic cell death (ICD) inducing the activation and stability of immunosuppressive regulatory T cells (Tregs). Dissecting the role of ALDH specific isoforms in the TME can open new scenarios in the cancer treatment. In this review, we summarize the current knowledge about the role of ALDH isoforms in solid tumors, in particular in association with therapy-resistance.
Roles of Pyroptosis-Related Gene Signature in Prediction of Endometrial Cancer Outcomes
Authors: Chen Yili , Liao Yuandong , Du Qiqiao , Shang Chunliang , Qin Shuhang , Lee Kaping , Zou Qiaojian , Liu Junxiu , Yao Shuzhong
Published: March 2022

Endometrial cancer (EC) is one of the most common gynecological malignancies in women, accompanied by the increasing incidence and decreasing age of onset. Pyroptosis plays an important role in the occurrence and development of malignant tumors. However, the relationship between pyroptosis-related genes and tumor prognosis remains unclear. In this study, analyzing the expression levels and survival data of 33 pyroptosis-related genes in the Cancer Genome Atlas (TCGA) between normal samples and tumor samples, we obtained six pyroptosis-related prognostic differentially expressed genes (DEGs). Then, through the least absolute shrinkage and selection operator (LASSO) regression analysis, a gene signature composed of six genes (GPX4, GSDMD, GSDME, IL6, NOD2 and PYCARD) was constructed and divided patients into high- and low-risk groups. Subsequently, Kaplan-Meier (KM) plot, receiver operating characteristic (ROC) curve and principal component analysis (PCA) in two cohorts demonstrated that the gene signature was an efficient independent prognostic indicator. The enrichment analysis and immune infiltration analysis indicated that the high-risk group generally has lower immune infiltrating cells and less active immune function. In short, we constructed and validated a pyroptosis-related gene signature to predict the prognosis of EC, which is correlated to immune infiltration and proposed to help the precise diagnosis and therapy of EC.
Survival of Patients With Cervical Cancer Treated With Definitive Radiotherapy or Concurrent Chemoradiotherapy According to Histological Subtype: A Systematic Review and Meta-Analysis
Authors: Yao Guorong , Qiu Jian , Zhu Fengjia , Wang Xiaoxie
Published: March 2022

Background

Cervical cancer is a leading cause of morbidity and mortality for women worldwide. Different histopathological cervical cancer subtypes (i.e., adenocarcinoma/adenosquamous carcinoma, and squamous cell carcinoma) are all treated similarly with definitive radiotherapy or concurrent chemoradiotherapy, but studies have reported differing survival prognoses. In this review and meta-analysis, we compared the disease-free and overall survivals of patients with cervical cancer treated with definitive radiotherapy or concurrent chemoradiotherapy according to the histopathological subtypes.

Objective

To compare the disease-free and overall survivals of patients with adenocarcinoma/adenosquamous carcinoma and squamous cell carcinoma cervical cancer treated with definitive radiotherapy or concurrent chemoradiotherapy.

Methods

We systematically searched the Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE academic databases following PRISMA guidelines. We identified publications to conduct a random-effects meta-analysis to evaluate the disease-free and overall survivals of patients with cervical adenocarcinoma/adenosquamous carcinoma and squamous cell carcinoma treated with definitive radiotherapy or concurrent chemoradiotherapy.

Results

From 963 studies, we found eight eligible ones with 13,859 patients with cervical cancer (mean age, 52.2 ± 7.9 years). Our meta-analysis revealed a poorer outcome of disease-free (hazard ratio, 1.51; 95% CI, 1.28–1.79) and overall (hazard ratio 1.41; 95% CI, 1.26–1.57) survivals for patients with adenocarcinoma/adenosquamous carcinoma undergoing definitive radiotherapy or concurrent chemoradiotherapy than for those with squamous cell carcinoma undergoing similar treatments. We also observed that larger tumor size and advanced tumor stage are also significant prognostic factors that adversely impact survival outcomes in cervical cancer patients undergoing definitive radiotherapy or concurrent chemoradiotherapy.

Conclusion

Our results show poor disease-free and overall survivals for patients with cervical cancer and adenocarcinoma/adenosquamous carcinoma than for those with squamous cell carcinoma after treatment with definitive radiotherapy or concurrent chemoradiotherapy. Our findings clarify the risks associated with the conventional management of cervical cancer according to the histological type.
Subversion of Phytomyxae Cell Communication With Surrounding Environment to Control Soilborne Diseases; A Case Study of Cytosolic Ca2+ Signal Disruption in Zoospores of Spongospora subterranea
Authors: Amponsah Jonathan , Tegg Robert S. , Thangavel Tamilarasan , Wilson Calum R.
Published: March 2022

Ca2+ signaling regulates physiological processes including chemotaxis in eukaryotes and prokaryotes. Its inhibition has formed the basis for control of human disease but remains largely unexplored for plant disease. This study investigated the role of Ca2+ signaling on motility and chemotaxis of Spongospora subterranea zoospores, responsible for root infections leading to potato root and tuber disease. Cytosolic Ca2+ flux inhibition with Ca2+ antagonists were found to alter zoospore swimming patterns and constrain zoospore chemotaxis, root attachment and zoosporangia infection. LaCl3 and GdCl3, both Ca2+ channel blockers, at concentrations ≥ 50 μM showed complete inhibition of zoospore chemotaxis, root attachment and zoosporangia root infection. The Ca2+ chelator EGTA, showed efficient chemotaxis inhibition but had relatively less effect on root attachment. Conversely the calmodulin antagonist trifluoperazine had lesser effect on zoospore chemotaxis but showed strong inhibition of zoospore root attachment. Amiloride hydrochloride had a significant inhibitory effect on chemotaxis, root attachment, and zoosporangia root infection with dose rates ≥ 150 μM. As expected, zoospore attachment was directly associated with root infection and zoosporangia development. These results highlight the fundamental role of Ca2+ signaling in zoospore chemotaxis and disease establishment. Their efficient interruption may provide durable and practical control of Phytomyxea soilborne diseases in the field.
Formation of Biofilm by Tetragenococcus halophilus Benefited Stress Tolerance and Anti-biofilm Activity Against S. aureus and S. Typhimurium
Authors: Yao Shangjie , Hao Liying , Zhou Rongqing , Jin Yao , Huang Jun , Wu Chongde
Published: March 2022

Tetragenococcus halophilus, a halophilic lactic acid bacterium (LAB), plays an important role in the production of high-salt fermented foods. Generally, formation of biofilm benefits the fitness of cells when faced with competitive and increasingly hostile fermented environments. In this work, the biofilm-forming capacity of T. halophilus was investigated. The results showed that the optimal conditions for biofilm formation by T. halophilus were at 3–9% salt content, 0–6% ethanol content, pH 7.0, 30°C, and on the surface of stainless steel. Confocal laser scanning microscopy (CLSM) analysis presented a dense and flat biofilm with a thickness of about 24 μm, and higher amounts of live cells were located near the surface of biofilm and more dead cells located at the bottom. Proteins, polysaccharides, extracellular-DNA (eDNA), and humic-like substances were all proved to take part in biofilm formation. Higher basic surface charge, greater hydrophilicity, and lower intracellular lactate dehydrogenase (LDH) activities were detected in T. halophilus grown in biofilms. Atomic force microscopy (AFM) imaging revealed that biofilm cultures of T. halophilus had stronger surface adhesion forces than planktonic cells. Cells in biofilm exhibited higher cell viability under acid stress, ethanol stress, heat stress, and oxidative stress. In addition, T. halophilus biofilms exhibited aggregation activity and anti-biofilm activity against Staphylococcus aureus and Salmonella Typhimurium. Results presented in the study may contribute to enhancing stress tolerance of T. halophilus and utilize their antagonistic activities against foodborne pathogens during the production of fermented foods.
The Role of Bacterial Membrane Vesicles in Human Health and Disease
Authors: Villageliu Daniel N. , Samuelson Derrick R.
Published: March 2022

Bacterial membrane vesicles (MVs) are nanoparticles derived from the membrane components of bacteria that transport microbial derived substances. MVs are ubiquitous across a variety of terrestrial and marine environments and vary widely in their composition and function. Membrane vesicle functional diversity is staggering: MVs facilitate intercellular communication by delivering quorum signals, genetic information, and small molecules active against a variety of receptors. MVs can deliver destructive virulence factors, alter the composition of the microbiota, take part in the formation of biofilms, assist in the uptake of nutrients, and serve as a chemical waste removal system for bacteria. MVs also facilitate host–microbe interactions including communication. Released in mass, MVs overwhelm the host immune system and injure host tissues; however, there is also evidence that vesicles may take part in processes which promote host health. This review will examine the ascribed functions of MVs within the context of human health and disease.
Developing Multi-Copy Chromosomal Integration Strategies for Heterologous Biosynthesis of Caffeic Acid in Saccharomyces cerevisiae
Authors: Qi Hang , Yu Long , Li Yuanzi , Cai Miao , He Jiaze , Liu Jiayu , Hao Luyao , Xu Haijin , Qiao Mingqiang
Published: March 2022

Caffeic acid, a plant-sourced phenolic compound, has a variety of biological activities, such as antioxidant and antimicrobial properties. The caffeic acid biosynthetic pathway was initially constructed in S. cerevisiae, using codon-optimized TAL (coTAL, encoding tyrosine ammonia lyase) from Rhodobacter capsulatus, coC3H (encoding p-coumaric acid 3-hydroxylase) and coCPR1 (encoding cytochrome P450 reductase 1) from Arabidopsis thaliana in 2 μ multi-copy plasmids to produce caffeic acid from glucose. Then, integrated expression of coTAL via delta integration with the POT1 gene (encoding triose phosphate isomerase) as selection marker and episomal expression of coC3H, coCPR1 using the episomal plasmid pLC-c3 were combined, and caffeic acid production was proved to be improved. Next, the delta and rDNA multi-copy integration methods were applied to integrate the genes coC3H and coCPR1 into the chromosome of high p-coumaric acid yielding strain QT3-20. The strain D9 constructed via delta integration outperformed the other strains, leading to 50-fold increased caffeic acid production in optimized rich media compared with the initial construct. The intercomparison between three alternative multi-copy strategies for de novo synthesis of caffeic acid in S. cerevisiae suggested that delta-integration was effective in improving caffeic acid productivity, providing a promising strategy for the production of valuable bio-based chemicals in recombinant S. cerevisiae.
Designing Allele-Specific Competitive-Extension PCR-Based Assays for High-Throughput Genotyping and Gene Characterization
Authors: Kalendar Ruslan , Shustov Alexandr V. , Akhmetollayev Ilyas , Kairov Ulykbek
Published: March 2022

Polymerase chain reaction (PCR) is a simple and rapid method that can detect nucleotide polymorphisms and sequence variation in basic research applications, agriculture, and medicine. Variants of PCR, collectively known as allele-specific PCR (AS-PCR), use a competitive reaction in the presence of allele-specific primers to preferentially amplify only certain alleles. This method, originally named by its developers as Kompetitive Allele Specific PCR (KASP), is an AS-PCR variant adapted for fluorescence-based detection of amplification results. We developed a bioinformatic tool for designing probe sequences for PCR-based genotyping assays. Probe sequences are designed in both directions, and both single nucleotide polymorphisms (SNPs) and insertion-deletions (InDels) may be targeted. In addition, the tool allows discrimination of up to four-allelic variants at a single SNP site. To increase both the reaction specificity and the discriminative power of SNP genotyping, each allele-specific primer is designed such that the penultimate base before the primer’s 3′ end base is positioned at the SNP site. The tool allows design of custom FRET cassette reporter systems for fluorescence-based assays. FastPCR is a user-friendly and powerful Java-based software that is freely available (http://primerdigital.com/tools/). Using the FastPCR environment and the tool for designing AS-PCR provides unparalleled flexibility for developing genotyping assays and specific and sensitive diagnostic PCR-based tests, which translates into a greater likelihood of research success.
Integrated Strategies of Diverse Feature Selection Methods Identify Aging-Based Reliable Gene Signatures for Ischemic Cardiomyopathy
Authors: Song Huafeng , Chen Shaoze , Zhang Tingting , Huang Xiaofei , Zhang Qiyu , Li Cuizhi , Chen Chunlin , Chen Shaoxian , Liu Dehui , Wang Jiawen , Tu Yingfeng , Wu Yueheng , Liu Youbin
Published: March 2022

Objective: Ischemic cardiomyopathy (ICM) is a major cardiovascular state associated with prominently increased morbidity and mortality. Our purpose was to detect reliable gene signatures for ICM through integrated feature selection strategies.

Methods: Transcriptome profiles of ICM were curated from the GEO project. Classification models, including least absolute shrinkage and selection operator (LASSO), support vector machine (SVM), and random forest, were adopted for identifying candidate ICM-specific genes for ICM. Immune cell infiltrates were estimated using the CIBERSORT method. Expressions of candidate genes were verified in ICM and healthy myocardial tissues via Western blotting. JC-1 staining, flow cytometry, and TUNEL staining were presented in hypoxia/reoxygenation (H/R)-stimulated H9C2 cells with TRMT5 deficiency.

Results: Following the integration of three feature selection methods, we identified seven candidate ICM-specific genes including ASPN, TRMT5, LUM, FCN3, CNN1, PCNT, and HOPX. ROC curves confirmed the excellent diagnostic efficacy of this combination of previous candidate genes in ICM. Most of them presented prominent interactions with immune cell infiltrates. Their deregulations were confirmed in ICM than healthy myocardial tissues. TRMT5 expressions were remarkedly upregulated in H/R-stimulated H9C2 cells. TRMT5 deficiency enhanced mitochondrial membrane potential and reduced apoptosis in H/R-exposed H9C2 cells.

Conclusion: Collectively, our findings identified reliable gene signatures through combination strategies of diverse feature selection methods, which facilitated the early detection of ICM and revealed the underlying mechanisms.
Exosomes in Age-Related Cognitive Decline: Mechanistic Insights and Improving Outcomes
Authors: Duggan Michael R. , Lu Anne , Foster Thomas C. , Wimmer Mathieu , Parikh Vinay
Published: March 2022

Aging is the most prominent risk factor for cognitive decline, yet behavioral symptomology and underlying neurobiology can vary between individuals. Certain individuals exhibit significant age-related cognitive impairments, while others maintain intact cognitive functioning with only minimal decline. Recent developments in genomic, proteomic, and functional imaging approaches have provided insights into the molecular and cellular substrates of cognitive decline in age-related neuropathologies. Despite the emergence of novel tools, accurately and reliably predicting longitudinal cognitive trajectories and improving functional outcomes for the elderly remains a major challenge. One promising approach has been the use of exosomes, a subgroup of extracellular vesicles that regulate intercellular communication and are easily accessible compared to other approaches. In the current review, we highlight recent findings which illustrate how the analysis of exosomes can improve our understanding of the underlying neurobiological mechanisms that contribute to cognitive variation in aging. Specifically, we focus on exosome-mediated regulation of miRNAs, neuroinflammation, and aggregate-prone proteins. In addition, we discuss how exosomes might be used to enhance individual patient outcomes by serving as reliable biomarkers of cognitive decline and as nanocarriers to deliver therapeutic agents to the brain in neurodegenerative conditions.
PKCε Activation Restores Loss of PKCε, Manganese Superoxide Dismutase, Vascular Endothelial Growth Factor, and Microvessels in Aged and Alzheimer’s Disease Hippocampus
Authors: Millien Guetchyn , Wang Huaixing , Zhang Zongxiu , Alkon Dan L. , Hongpaisan Jarin
Published: March 2022

Vascular endothelial dysfunction and capillary loss are currently considered to be a primary phenotype of normal human aging and Alzheimer’s disease (AD). Activation of protein kinase C (PKCε) improves several molecular, cellular, physiological, and behavioral endpoints, yet it is not known whether a loss of PKCε activity occurs in the microvascular endothelium in aged and AD hippocampi, whether this loss contributes to microvascular change, or whether activation of PKCε protects against microvascular damage, an early change that induces age-associated memory defect and AD. We investigated the effect of the PKCε activation on microvascular loss in the hippocampus, important for memory storage. In cultured human brain microvascular endothelial cells, tert-butyl hydroperoxide induced oxidative stress and a decrease in manganese superoxide dismutase (MnSOD) mRNA and protein expression that were blocked by the antioxidant drugs. The PKCε activators bryostatin and DCPLA methyl ester increased PKCε, associated with an increase in MnSOD mRNA and its protein as well as vascular endothelial growth factor (VEGF), which was inhibited by the mRNA-stabilizing HuR inhibitors. In rats (>24 months old) and AD transgenic mice Tg2576 (5 months old), bryostatin or DCP-LA prevented a decrease in vascular PKCε, MnSOD, and VEGF and prevented microvascular loss and age-related memory impairment. An autopsy-confirmed AD hippocampus showed a decrease in PKCε and MnSOD mRNAs and their proteins and VEGF as well as in microvascular density compared to non-AD controls. In conclusion, the PKCε activation can rescue a decrease in PKCε, MnSOD, and VEGF via posttranscription regulation and alleviate oxidative stress, and in doing so, prevent microvascular loss during aging and AD.
Quantification of Brain β-Amyloid Load in Parkinson's Disease With Mild Cognitive Impairment: A PET/MRI Study
Authors: Garon Michela , Weis Luca , Fiorenzato Eleonora , Pistonesi Francesca , Cagnin Annachiara , Bertoldo Alessandra , Anglani Mariagiulia , Cecchin Diego , Antonini Angelo , Biundo Roberta
Published: March 2022

Background

Mild cognitive impairment in Parkinson's disease (PD-MCI) is associated with faster cognitive decline and conversion to dementia. There is uncertainty about the role of β-amyloid (Aβ) co-pathology and its contribution to the variability in PD-MCI profile and cognitive progression.

Objective

To study how presence of Aβ affects clinical and cognitive manifestations as well as regional brain volumes in PD-MCI.

Methods

Twenty-five PD-MCI patients underwent simultaneous PET/3T-MRI with [18F]flutemetamol and a clinical and neuropsychological examination allowing level II diagnosis. We tested pairwise differences in motor, clinical, and cognitive features with Mann–Whitney U test. We calculated [18F]flutemetamol (FMM) standardized uptake value ratios (SUVR) in striatal and cortical ROIs, and we performed a univariate linear regression analysis between the affected cognitive domains and the mean SUVR. Finally, we investigated differences in cortical and subcortical brain regional volumes with magnetic resonance imaging (MRI).

Results

There were 8 Aβ+ and 17 Aβ- PD-MCI. They did not differ for age, disease duration, clinical, motor, behavioral, and global cognition scores. PD-MCI-Aβ+ showed worse performance in the overall executive domain (p = 0.037). Subcortical ROIs analysis showed significant Aβ deposition in PD-MCI-Aβ+ patients in the right caudal and rostral middle frontal cortex, in precuneus, in left paracentral and pars triangularis (p < 0.0001), and bilaterally in the putamen (p = 0.038). Cortical regions with higher amyloid load correlated with worse executive performances (p < 0.05). Voxel-based morphometry (VBM) analyses showed no between groups differences.

Conclusions

Presence of cerebral Aβ worsens executive functions, but not motor and global cognitive abilities in PD-MCI, and it is not associated with middle-temporal cortex atrophy. These findings, together with the observation of significant proportion of PD-MCI-Aβ-, suggest that Aβ may not be the main pathogenetic determinant of cognitive deterioration in PD-MCI, but it would rather aggravate deficits in domains vulnerable to Parkinson primary pathology.
MOG Antibody-Associated Disorders Following SARS-CoV-2 Vaccination: A Case Report and Literature Review
Authors: Matsumoto Yuki , Ohyama Ayane , Kubota Takafumi , Ikeda Kensuke , Kaneko Kimihiko , Takai Yoshiki , Warita Hitoshi , Takahashi Toshiyuki , Misu Tatsuro , Aoki Masashi
Published: March 2022

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorder (MOGAD) is a newly identified autoimmune demyelinating disorder that is often associated with acute disseminated encephalomyelitis and usually occurs postinfection or postvaccination. Here we report a case of MOGAD after mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. A previously healthy 68-year-old woman presented to our department with gradually worsening numbness on the right side of her face, which began 14 days after her second dose of an mRNA-1273 vaccination. The patient's brain MRI revealed a right cerebellar peduncle lesion with gadolinium enhancement, a typical finding of MOGAD. A neurological examination revealed paresthesia on her right V2 and V3 areas. Other neurological examinations were unremarkable. Laboratory workups were positive for serum MOG-IgG as assessed by live cell-based assays and the presence of oligoclonal bands in the cerebrospinal fluid (CSF). The patient's serum test results for cytoplasmic-antineutrophil cytoplasmic antibodies, perinuclear-cytoplasmic-antineutrophil cytoplasmic antibodies, GQ1b-antibodies, and aquaporin-4 antibodies (AQP4-IgG) were all negative. Tests for soluble interleukin (IL)-2 receptors in the serum, IL-6 in the CSF and skin pricks, and angiotensin converting enzyme tests were all unremarkable. The patient was diagnosed with MOGAD after receiving an mRNA SARS-CoV-2 vaccination. After two courses of intravenous methylprednisolone treatment, the patient's symptoms improved and her cerebellar peduncle lesion shrunk slightly without gadolinium enhancement. To date, there have only been two cases of monophasic MOGAD following SARS-CoV-2 vaccination, including both the ChAdOx1 nCOV-19 and mRNA-1273 vaccines, and the prognosis is generally similar to other typical MOGAD cases. Although the appearance of MOG antibodies is relatively rare in post-COVID-19–vaccine demyelinating diseases, MOGAD should be considered in patients with central nervous system (CNS) demyelinating diseases after receiving a SARS-CoV-2 vaccine.
Clinical Significance of Volume Status in Body Composition and Physical Performance Measurements in Hemodialysis Patients
Authors: Kim Jun Chul , Do Jun Young , Kang Seok Hui
Published: March 2022

Introduction

This study aimed to evaluate the association between volume status and body composition or physical performance measurements in hemodialysis patients.

Methods

A total of 84 patients were enrolled in this study. The participants were divided into tertiles based on the edema index (extracellular water/total body water): low, middle, and high tertiles. Serum albumin and serum high-sensitivity C-reactive protein levels were measured. The appendicular lean mass index (ALM/Ht2, kg/m2) was measured using dual-energy X-ray absorptiometry. The thigh muscle area index (TMA/Ht2, cm2/m2) was measured using CT. Extracellular and total body water and phase angles were obtained using bioimpedance analysis. The results of the subjective global assessment (SGA), hand-grip strength (HGS), gait speed (GS), short physical performance battery (SPPB), sit-to-stand for 30-second (STS30) test, timed up and go (TUG), sit-to-stand test performed five times (STS5), and 6-minute walk (6-MW) tests were also evaluated.

Results

On the univariate analysis, the SGA score and phase angle in the high tertile group were the lowest among the three groups. On multivariate analysis, TMA/Ht2 and phase angle in the high tertile were the lowest among the three groups. Inverse correlations were observed between edema index and TMA/Ht2, SGA score, phase angle, HGS, GS, SPPB, STS30, or 6-MW. Positive correlations were observed between the edema index and the STS5 or TUG test. The sensitivity and specificity for predicting low GS were 34.5 and 89.7%, respectively. The values for predicting low SPPB were 68.0 and 79.7%, respectively.

Conclusion

This study demonstrates that high volume status may be associated with decreased muscle mass and physical performance regardless of inflammatory or nutritional status.