bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence Of Financial Literacy Towards Risk Tolerance
Authors: Hui-Nee Au Yong  , Kock-Lim Tan
Published: March 2021

The importance of financial literacy in promoting good financial behaviour has been established in Malaysia. Nonetheless, a study that specifically analyses youth is still needed. This study focuses on Malaysian youths’ financial literacy and financial behaviour. It is alsoexpected that financial behaviour and financial literacy significantly among those from different parental, gender and income backgrounds. A quantitative approach was adopted, utilising questionnaire survey as the research instrument. The male respondentswere more financially literate. Findingsindicated that parent backgrounds, predicted students’ financial behaviour. This study provides valueable results reflecting parental influence had a significant influence on financial behaviour. This study suggests awareness programmes to enhance the general financial literacy especially among youths.
Spiritual Leadership And Organizational Citizenship Behavior: Exploring The Conditional Effects Of Self-Determination And Confucian Mindset
Authors: William D. Hunsaker
Published: March 2021

Today’s workers are increasingly expected to work autonomously while also working beyond assigned responsibilities as organizational citizens. Effective leadership facilitates this process. This paper proposed that the intrinsic motivational aspects of self-determination mediate the relationship between spiritual leadership and organizational citizenship behavior (OCB). Moreover, given that the effectiveness of leadership theory requires a congruency with cultural values when testing in non-western cultures, this paper proposed that Confucian values moderate the relationship between one’s perceived self-determination and OCBs in Confucian-centric cultures. Results confirmed that self-determination mediated the proposed relationship. Additionally, the results confirmed that Confucian values moderate the relationship between self-determination and citizenship behavior to the organization(OCBO). The results of this study increase our understanding of how and under what conditions spiritual leadership influences employee participation in citizenship behaviors.
The Importance of Farm Animal Health and Natural Behaviors to Livestock Farmers: Findings From a Factorial Survey Using Vignettes
Authors: Vigors Belinda , Ewing David A. , Lawrence Alistair B.
Published: March 2021

There is increasing interest in enabling positive experiences, not just minimizing negative experiences, to improve the welfare of farmed animals. This has influenced the growth of private agri-food standards and supported arguments to integrate animal welfare into policy on sustainability and climate change. However, much research finds that farmers predominantly focus on the minimization of negatives (i.e., health issues). This may impact the positioning of farmers within these wider societal debates, affecting their social license to farm. It is thus important to better understand farmers' priorities relating to the minimization of negative factors (e.g., health issues) and the promotion of positive experiences (i.e., natural behaviors). A novel 2 × 2 factorial survey using vignettes, which experimentally manipulated health (health issues minimized/not minimized) and natural behavior (natural behaviors promoted/not promoted) provision, was completed by livestock farmers (n= 169), mostly with extensive systems, in the UK and Republic of Ireland. The majority (88%) considered “minimizing health issues” to be the most important factor for animal well-being. However, the overall welfare of animals was judged to be highest when both health and natural behaviors were supported. Several individual characteristics, including farming sector, production system, gender, belief in animal mind and business type influenced how participants judged the welfare of animals and the level of importance they gave to health and natural behaviors. Findings suggest that although farmers prioritize the minimization of health issues they want animals to be both healthy and able to express natural behaviors, and individual characteristics are important for understanding farmers' welfare-related judgements.
SAXS/WAXS Investigation of Amyloid-β(16-22) Peptide Nanotubes
Authors: Narayanan Theyencheri , Rüter Axel , Olsson Ulf
Published: March 2021

This brief report presents an X-ray scattering investigation of self-assembled nanotubes formed by a short peptide. X-ray scattering methods enable multiscale structural elucidation of these nanotubes in solution under the same conditions involved in the self-assembly process. In particular, the dimensions of nanotubes and the crystalline organization within their walls can be determined quantitatively. This is illustrated in the case of amyloid-β(16-22) peptide nanotubes.
4D BIM Simulation Guideline for Construction Visualization and Analysis of Renovation Projects: A Case Study
Authors: Alzarrad M. Ammar , Moynihan Gary P. , Parajuli Aakash , Mehra Mayuri
Published: March 2021

With the BIM applications on fast-track, it is being used for new construction and recently being utilized for renovation, retrofitting, and repairing purposes. Although many studies have been conducted to identify BIM capabilities in renovation projects, the application of 4D BIM for both the demolition and the construction phases of renovation projects is still underdeveloped. This paper presents a guideline to apply 4D BIM for complicated renovation projects that include demolition and construction phases. The paper represents a step-by-step process from the extraction of information from a 2D model and converting it into a 4D model. The proposed guideline will help CAD users to apply 4D BIM for complicated renovation model. A real case application is analyzed to demonstrate the potential of the presented guideline. The research results show that the proposed guideline could assist in construction management by finding out inappropriate sequences in schedule, conducting evaluation of issues related to constructability, and identifying disagreements in time and space. The proposed guideline could help identify errors in construction scheduling, which have the potential to reduce project cost and duration.
Transcriptional Responses of Beauveria bassiana Blastospores Cultured Under Varying Glucose Concentrations
Authors: Mascarin Gabriel Moura , Iwanicki Natasha Sant’Anna , Ramirez Jose Luis , Delalibera Ítalo , Dunlap Christopher A.
Published: March 2021

Culturing the entomopathogenic fungus, Beauveria bassiana, under high glucose concentrations coupled with high aeration results in a fungal developmental shift from hyphal growth to mostly blastospores (yeast-like cells). The underlying molecular mechanisms involved in this shift remain elusive. A systematic transcriptome analysis of the differential gene expression was preformed to uncover the fungal transcriptomic response to osmotic and oxidative stresses associated with the resulting high blastospore yield. Differential gene expression was compared under moderate (10% w/v) and high (20% w/v) glucose concentrations daily for three days. The RNAseq-based transcriptomic results depicted a higher proportion of downregulated genes when the fungus was grown under 20% glucose than 10%. Additional experiments explored a broader glucose range (4, 8, 12, 16, 20% w/v) with phenotype assessment and qRT-PCR transcript abundance measurements of selected genes. Antioxidant, calcium transport, conidiation, and osmosensor-related genes were highly upregulated in higher glucose titers (16-20%) compared to growth in lower glucose (4-6%) concentrations. The class 1 hydrophobin gene (Hyd1) was highly expressed throughout the culturing. Hyd1 is known to be involved in spore coat rodlet layer assembly, and indicates that blastospores or another cell type containing hydrophobin 1 is expressed in the haemocoel during the infection process. Furthermore, we found implications of the HOG signaling pathway with upregulation of homologous genes Ssk2 and Hog1 for all fermentation time points under hyperosmotic medium (20% glucose). These findings expand our knowledge of the molecular mechanisms behind blastospore development and may help facilitate large-scale industrial production of B. bassiana blastospores for pest control applications.
Differential Cell Line Susceptibility to Crimean-Congo Hemorrhagic Fever Virus
Authors: Dai Shiyu , Wu Qiaoli , Wu Xiaoli , Peng Cheng , Liu Jia , Tang Shuang , Zhang Tao , Deng Fei , Shen Shu
Published: March 2021

Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne viral disease of global concerns due to the increasing incidence and lack of effective treatments. The causative agent, CCHF virus (CCHFV), has been characterized for years; however, its tropism in cell lines of different host and tissue origins remains unclear. This study characterized the susceptibility of 16 human and 6 animal cell lines to CCHFV. Increased viral load and viral nucleoprotein expression, and productive CCHFV replication were detected in human vascular (HUVEC), renal (SW-13 and HEK-293), hepatic (Huh7), and cerebral (U-87 MG) cell lines, which were considered CCHFV-highly permissive cell lines. Renal cell lines derived from monkey and dog could also support CCHFV replication. This study evaluated the susceptibility of different cell lines to CCHFV and identified CCHFV-permissive cell lines. Our findings raise concerns regarding the use of cell lines in ex vivo studies of CCHFV and may have important implications for further fundamental research, which would promote understanding of CCHFV pathogenesis and transmission, as well as benefit designing strategies for disease prevention and control.
Therapeutic Efficacy of Excretory-Secretory Products of Trichinella spiralis Adult Worms on Sepsis-Induced Acute Lung Injury in a Mouse Model
Authors: Li Huihui , Qiu Dapeng , Yang Huijuan , Yuan Yuan , Wu Lingqin , Chu Liang , Zhan Bin , Wang Xiaoli , Sun Yan , Xu Wei , Yang Xiaodi
Published: March 2021

Acute lung injury (ALI) is a common complication of systemic inflammation or sepsis with high morbidity and mortality. Although many studies have confirmed that helminth-derived proteins had strong immunomodulatory functions and could be used to treat inflammatory diseases, there is no report on the therapeutic effect of excretory-secretory products of Trichinella spiralis adult worms (Ts-AES) on sepsis-induced ALI. In this study, the therapeutic efficacy of Ts-AES on sepsis-induced ALI and the underlying immunological mechanism and the signaling pathway were investigated. The results indicated that after being treated with Ts-AES, the survival rate of mice with CLP-induced sepsis was significantly increased to 50% for 72 hours after CLP surgery compared to PBS control group with all mice died. The sepsis-induced ALI was largely mitigated characterized by reduced inflammation cell infiltration and pathological changes in lung tissue, with decreased lung injury scores and lung wet/dry weight ratio. The therapeutic efficacy of Ts-AES is associated with stimulated Tregs response with increased regulatory cytokines IL-10 and TGF-β and downregulated pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). The expression of HMGB1, TLR2 and MyD88 in lung tissue was inhibited after treatment of Ts-AES. Our results demonstrated that Ts-AES play an important role in immunomodulation and confer a therapeutic effect on sepsis-induced ALI through inhibiting pro-inflammatory cytokines. The activation of Tregs and increased level of regulatory cytokines IL-10 and TGF-β are possibly involved in the immunomodulatory functions of Ts-AES through HMGB1/TLR2/MyD88 signal pathway. The findings suggest Ts-AES is a potential therapeutic agent for prevention and treatment of sepsis-induced ALI and other inflammatory diseases.
Hemodynamic Profiles Before and After Surgery in Bicuspid Aortic Valve Disease—A Systematic Review of the Literature
Authors: Cave Daniel G. W. , Panayiotou Hannah , Bissell Malenka M.
Published: March 2021

Bicuspid aortic valve (BAV) disease presents a unique management challenge both pre- and post-operatively. 4D flow MRI offers multiple tools for the assessment of the thoracic aorta in aortic valve disease. In particular, its assessment of flow patterns and wall shear stress have led to new understandings around the mechanisms of aneurysm development in BAV disease. Novel parameters have now been developed that have the potential to predict pathological aortic dilatation and may help to risk stratify BAV patients in future. This systematic review analyses the current 4D flow MRI literature after aortic valve and/or ascending aortic replacement in bicuspid aortic valve disease. 4D flow MRI has also identified distinct challenges posed by this cohort at the time of valve replacement compared to standard management of tri-leaflet disorders, and may help tailor the type and timing of replacement. Eccentric pathological flow patterns seen after bioprosthetic valve implantation, but not with mechanical prostheses, might be an important future consideration in intervention planning. 4D flow MRI also has promising potential in supporting the development of artificial valve prostheses and aortic conduits with more physiological flow patterns.
Efficacy of Various Hypoglycemic Agents in the Treatment of Patients With Nonalcoholic Liver Disease With or Without Diabetes： A Network Meta-Analysis
Authors: Lian Jingxuan , Fu Jianfang
Published: March 2021

Objective

To comprehensively evaluate and compare the therapeutic effects of various hypoglycemic agents in NAFLD patients with or without diabetes.

Methods

All literature from the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Clinical Trials was searched, and the language was limited to English. Two reviewers independently assessed study eligibility, continuous data extraction, and independent assessment of bias risk. Our primary outcomes were alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglyceride levels, while our secondary outcomes were high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels, body weight, BMI, and fasting glucose and glycosylated hemoglobin (HbA1c) levels.

Results

The review identified 20 eligible trials that met the inclusion criteria. We found that, compared to other drugs, thiazolidinediones, especially pioglitazone, had a greater effect on the levels of ALT (-8.01 (95% CI -14.3 to 2.02)) and AST (-5.0 (95% CI -9.21 to -1,22)) and other biological indicators, but they were also associated with an increased risk of weight gain (3.62 (95% CI 2.25 to 4.99) and increased BMI (0.59 (95% Cl -0.13 to 1.29). GLP1 RAs and metformin also had better therapeutic effects than other drugs as measured by the levels of ALT (liraglutide: -9.36 (95% Cl -18 to -0.34), metformin: -2.84 (95% CI -11.09 to 5.28)) and AST (liraglutide: -5.14 (95% CI -10.69 to 0.37), metformin: -2.39 (95% CI -7.55, 2.49)) and other biological indicators.

Conclusion

Despite the significant risk of weight gain, thiazolidinediones, especially pioglitazone, are beneficial in normalizing liver and glucose metabolism in NAFLD patients. In clinical practice, we believe that GLP1 RAs such as liraglutide and exenatide or metformin can be used in combination to offset the risk of weight gain associated with thiazolidinediones. However, long-term studies are still needed to verify the efficacy and safety of individual hypoglycemic agents.

Systematic Review Registration

[PROSPERO], identifier [CRD42020212025].
Anxiety, Health Self-Perception, and Worry About the Resurgence of COVID-19 Predict Fear Reactions Among Genders in the Cuban Population
Authors: Broche-Pérez Yunier , Fernández-Fleites Zoylen , Fernández-Castillo Evelyn , Jiménez-Puig Elizabeth , Vizcaíno-Escobar Annia Esther , Ferrer-Lozano Dunia M. , Martínez-Rodríguez Lesnay , Martín-González Reinier
Published: March 2021

The resurgence of COVID-19 could deepen the psychological impacts of the pandemic which poses new challenges for mental health professionals. Among the actions that should be prioritized is the monitoring of the groups that have shown greater psychological vulnerability during the first stage of the pandemic. The first aim of our study is to explore the fear reactions to COVID-19 between genders during the second wave of the outbreak in Cuba. Second, establish possible predictors of fear of COVID-19 in relation to gender. Specifically, we will evaluate how anxiety related to COVID-19, health self-perception, and worry about the resurgence of COVID-19 predict fear reactions among women and men in the Cuban population. A cross-sectional online study was designed. The research was conducted between August 16 and October 18, 2020. A total of 373 people completed the online survey. A socio-demographic questionnaire, the Fear of COVID-19 Scale and the Coronavirus Anxiety Scale were used. An independent-samplest-test was conducted to compare the fear, worry, anxiety and self-perceived health scores, between genders. The relationship between those variables and fear of COVID-19, was investigated using Pearson correlation coefficient. Finally, multiple linear regression was used to evaluate the possible associations (predictors) related to fear of COVID-19. In our study, women, compared to men, presented greater fear reactions, greater concern about resurgence of COVID-19 and poorer self-perceived health. Anxiety reactions in our sample showed no differences between genders. In women, anxiety of COVID-19, worry about resurgence of COVID-19, and self-perceived health are associated with fear reactions to COVID-19. In the case of men, the self-perceived health showed no associations with fear reactions. Our results confirm the results of several related investigations during the first wave of the pandemic where women have shown greater psychological vulnerability compared to men. However, we cannot rule out that the real impact of the pandemic on mental health in men is much greater than that described by the studies conducted to date. Additional studies are needed on the psychological impact of COVID-19 on men.
Advances in Understanding the Roles of CD244 (SLAMF4) in Immune Regulation and Associated Diseases
Authors: Sun Lin , Gang Xiaokun , Li Zhuo , Zhao Xue , Zhou Tong , Zhang Siwen , Wang Guixia
Published: March 2021

Proteins in the signaling lymphocytic activating molecule (SLAM) family play crucial roles in regulating the immune system. CD244 (SLAMF4) is a protein in this family, and is also a member of the CD2 subset of the immunoglobulin (Ig) superfamily. CD244 is a cell surface protein expressed by NK cells, T cells, monocytes, eosinophils, myeloid-derived suppressor cells, and dendritic cells. CD244 binds to the ligand CD48 on adjacent cells and transmits stimulatory or inhibitory signals that regulate immune function. In-depth studies reported that CD244 functions in many immune-related diseases, such as autoimmune diseases, infectious diseases, and cancers, and its action is essential for the onset and progression of these diseases. The discovery of these essential roles of CD244 suggests it has potential as a prognostic indicator or therapeutic target. This review describes the molecular structure and function of CD244 and its roles in various immune cells and immune-related diseases.
Effects of Nutrient Management Scenarios on Marine Eutrophication Indicators: A Pan-European, Multi-Model Assessment in Support of the Marine Strategy Framework Directive
Authors: Friedland René , Macias Diego , Cossarini Gianpiero , Daewel Ute , Estournel Claude , Garcia-Gorriz Elisa , Grizzetti Bruna , Grégoire Marilaure , Gustafson Bo , Kalaroni Sofia , Kerimoglu Onur , Lazzari Paolo , Lenhart Hermann , Lessin Gennadi , Maljutenko Ilja , Miladinova Svetla , Müller-Karulis Bärbel , Neumann Thomas , Parn Ove , Pätsch Johannes , Piroddi Chiara , Raudsepp Urmas , Schrum Corinna , Stegert Christoph , Stips Adolf , Tsiaras Kostas , Ulses Caroline , Vandenbulcke Luc
Published: March 2021

A novel pan-European marine model ensemble was established, covering nearly all seas under the regulation of the Marine Strategy Framework Directive (MSFD), with the aim of providing a consistent assessment of the potential impacts of riverine nutrient reduction scenarios on marine eutrophication indicators. For each sea region, up to five coupled biogeochemical models from institutes all over Europe were brought together for the first time. All model systems followed a harmonised scenario approach and ran two simulations, which varied only in the riverine nutrient inputs. The load reductions were evaluated with the catchment model GREEN and represented the impacts due to improved management of agriculture and wastewater treatment in all European river systems. The model ensemble, comprising 15 members, was used to assess changes to the core eutrophication indicators as defined within MSFD Descriptor 5. In nearly all marine regions, riverine load reductions led to reduced nutrient concentrations in the marine environment. However, regionally the nutrient input reductions led to an increase in the non-limiting nutrient in the water, especially in the case of phosphate concentrations in the Black Sea. Further core eutrophication indicators, such as chlorophyll-a, bottom oxygen and the Trophic Index TRIX, improved nearly everywhere, but the changes were less pronounced than for the inorganic nutrients. The model ensemble displayed strong consistency and robustness, as most if not all models indicated improvements in the same areas. There were substantial differences between the individual seas in the speed of response to the reduced nutrient loads. In the North Sea ensemble, a stable plateau was reached after only three years, while the simulation period of eight years was too short to obtain steady model results in the Baltic Sea. The ensemble exercise confirmed the importance of improved management of agriculture and wastewater treatments in the river catchments to reduce marine eutrophication. Several shortcomings were identified, the outcome of different approaches to compute the mean change was estimated and potential improvements are discussed to enhance policy support. Applying a model ensemble enabled us to obtain highly robust and consistent model results, substantially decreasing uncertainties in the scenario outcome.
Impediments to Understanding Seagrasses’ Response to Global Change
Authors: Rock Brianna M. , Daru Barnabas H.
Published: March 2021

Uncertainties from sampling biases present challenges to ecologists and evolutionary biologists in understanding species sensitivity to anthropogenic climate change. Here, we synthesize possible impediments that can constrain research to assess present and future seagrass response from climate change. First, our knowledge of seagrass occurrence information is prevalent with biases, gaps and uncertainties that can influence inferences on species response to global change. Second, research on seagrass diversity has been focused on species-level metrics that can be measured with data from the present – but rarely accounting for the shared phylogenetic relationships and evolutionary distinctiveness of species despite species evolved and diversified from shared ancestors. Third, compared to the mass production of species occurrence records, computational tools that can analyze these datasets in a reasonable amount of time are almost non-existent or do not scale well in terms of computer time and memory. These impediments mean that scientists must work with incomplete information and often unrepresentative data to predict how seagrass diversity might change in the future. We discuss these shortfalls and provide a framework for overcoming the impediments and diminishing the knowledge gaps they generate.
Comparison of Oyster Aquaculture Methods and Their Potential to Enhance Microbial Nitrogen Removal From Coastal Ecosystems
Authors: Mara Paraskevi , Edgcomb Virginia P. , Sehein Taylor R. , Beaudoin David , Martinsen Chuck , Lovely Christina , Belcher Bridget , Cox Rebecca , Curran Meghan , Farnan Claire , Giannini Peter , Lott Sarah , Paquette Kyle , Pinckney Anna , Schafer Natalie , Surgeon-Rogers Tonna-Marie , Rogers Daniel R.
Published: March 2021

Coastal ecosystems are impacted by excessive nutrient inputs that cause degradation of water quality and impairments of ecosystem functioning. Regulatory and management efforts to enhance nutrient export from coastal ecosystems include sustainable oyster aquaculture that removes nitrogen in the form of oyster biomass and increases particulate export to underlying sediments where increased organic material may enhance microbial denitrification. To better understand the impacts of oyster aquaculture on nitrogen removal, we examined bacterial processes in sediments underlying three of the most common aquaculture methods that vary in the proximity of oysters to the sediments. Sediment samples underlying sites managed with these different aquaculture methods were examined using the 16S rRNA gene to assess microbial community structure, gene expression analyses to examine nitrogen and sulfur cycling genes, and nitrogen gas flux measurements. All sites were located in the same hydrodynamic setting within Waquoit Bay, MA during 2018 and 2019. Although sediments under the different oyster farming practices showed similar communities, ordination analysis revealed discrete community groups formed along the sampling season. Measured N2 fluxes and expression of key genes involved in denitrification, anaerobic ammonium oxidation (anammox), and dissimilatory nitrate reduction to ammonium (DNRA) increased during mid-summer and into fall in both years primarily under bottom cages. While all three oyster growing methods enhanced nitrogen removal relative to the control site, gene expression data indicate that the nitrogen retaining process of DNRA is particularly enhanced after end of July under bottom cages, and to a lesser extent, under suspended and floating bags. The choice of gear can also potentially increase processes that induce nitrogen retention in the form of ammonia in the underlying sediments over time, thus causing deviations from predicted nitrogen removal. If nitrogen removal is a primary objective, monitoring for these shifts is essential for making decisions about siting and size of aquaculture sites from year to year.
Winter Carnivory and Diapause Counteract the Reliance on Ice Algae by Barents Sea Zooplankton
Authors: Kohlbach Doreen , Schmidt Katrin , Hop Haakon , Wold Anette , Al-Habahbeh Amalia Keck , Belt Simon T. , Woll Matthias , Graeve Martin , Smik Lukas , Atkinson Angus , Assmy Philipp
Published: March 2021

The Barents Sea is a hotspot for environmental change due to its rapid warming, and information on dietary preferences of zooplankton is crucial to better understand the impacts of these changes on food-web dynamics. We combined lipid-based trophic marker approaches, namely analysis of fatty acids (FAs), highly branched isoprenoids (HBIs) and sterols, to compare late summer (August) and early winter (November/December) feeding of key Barents Sea zooplankters; the copepods Calanus glacialis, C. hyperboreus and C. finmarchicus and the amphipods Themisto libellula and T. abyssorum. Based on FAs, copepods showed a stronger reliance on a diatom-based diet. Phytosterols, produced mainly by diatoms, declined from summer to winter in C. glacialis and C. hyperboreus, indicating the strong direct linkage of their feeding to primary production. By contrast, C. finmarchicus showed evidence of year-round feeding, indicated by the higher winter carnivory FA ratios of 18:1(n-9)/18:1(n-7) than its larger congeners. This, plus differences in seasonal lipid dynamics, suggests varied overwintering strategies among the copepods; namely diapause in C. glacialis and C. hyperboreus and continued feeding activity in C. finmarchicus. Based on the absence of sea ice algae-associated HBIs (IP25 and IPSO25) in the three copepod species during both seasons, their carbon sources were likely primarily of pelagic origin. In both amphipods, increased FA carnivory ratios during winter indicated that they relied strongly on heterotrophic prey during the polar night. Both amphipod species contained sea ice algae-derived HBIs, present in broadly similar concentrations between species and seasons. Our results indicate that sea ice-derived carbon forms a supplementary food rather than a crucial dietary component for these two amphipod species in summer and winter, with carnivory potentially providing them with a degree of resilience to the rapid decline in Barents Sea (winter) sea-ice extent and thickness. The weak trophic link of both zooplankton taxa to sea ice-derived carbon in our study likely reflects the low abundance and quality of ice-associated carbon during late summer and the inaccessibility of algae trapped inside the ice during winter.
The Genetic Control of the Rheumatic Heart: Closing the Genotype-Phenotype Gap
Authors: Abdallah Atiyeh M. , Abu-Madi Marawan
Published: March 2021

Rheumatic heart disease (RHD) is a heritable inflammatory condition characterized by carditis, arthritis, and systemic disease. Although remaining neglected, the last 3 years has seen some promising advances in RHD research. Whilst it is clear that RHD can be triggered by recurrent group A streptococcal infections, the mechanisms driving clinical progression are still poorly understood. This review summarizes our current understanding of the genetics implicated in this process and the genetic determinants that predispose some people to RHD. The evidence demonstrating the importance of individual cell types and cellular states in delineating causal genetic variants is discussed, highlighting phenotype/genotype correlations where possible. Genetic fine mapping and functional studies in extreme phenotypes, together with large-scale omics studies including genomics, transcriptomics, epigenomics, and metabolomics, are expected to provide new information not only on RHD but also on the mechanisms of other autoimmune diseases and facilitate future clinical translation.
Xylanase Supplementation Modulates the Microbiota of the Large Intestine of Pigs Fed Corn-Based Fiber by Means of a Stimbiotic Mechanism of Action
Authors: Petry Amy L. , Patience John F. , Huntley Nichole F. , Koester Lucas R. , Bedford Michael R. , Schmitz-Esser Stephan
Published: March 2021

This research tested the hypothesis that xylanase modulates microbial communities within the large intestine of growing pigs fed corn-based fiber through a stimbiotic mechanism(s) of action (MOA). Sixty gilts were blocked by initial body weight, individually housed, and randomly assigned to one of four dietary treatments (n = 15): a low-fiber (LF) control, a high-fiber (HF) control containing 30% corn bran, HF+100 mg/kg xylanase (HF+XY), and HF+50 mg/kg arabinoxylan-oligosaccharide (HF+AX). Pigs were fed dietary treatments for 46 days. On day 46, pigs were euthanized, and mucosa and lumen contents were collected from the cecum and the colon. The V4 region of 16S rRNA genes was sequenced and clustered into 5,889, 4,657, 2,822, and 4,516 operational taxonomic units (OTUs), in the cecal contents and mucosa and colonic contents and mucosa, respectively. In cecal contents, HF+XY increased measures of α-diversity compared to LF (p < 0.001). Relative to LF, HF increased the prevalence of 44, 36, 26, and 8, and decreased 19, 9, 21, and 10, of the 200 most abundant OTUs from the cecal contents and mucosa and colonic contents and mucosa, respectively (Q < 0.05). Compared to LF, HF increased the abundance of OTUs from the Treponema_2, Ruminococcus_1 genera, from the Lachnospiraceae, Ruminococcaceae, and Prevotellaceae families. In contrast, relative to LF, HF decreased Turicibacter and Lactobacillus in the cecal contents, and Megasphaera and Streptococcus in the mucosa. Relative to HF, HF+XY increased 32, 16, 29, and 19 and decreased 27, 11, 15, and 10 of the 200 most abundant OTUs from the cecal contents and mucosa and colonic contents and mucosa, respectively (Q < 0.05). The addition of xylanase to HF further increased the abundance of OTUs from the Lachnospiraceae and Ruminococcaceae families across the large intestine. Compared to HF, HF+XY increased the abundance of Lactobacillus, Bifidobacterium, and Faecalibacterium among all locations (Q < 0.05). However, HF+AX did not increase the prevalence of these genera in the large intestine. Supplementing xylanase to HF increased hidden-state predictions of microbial enzymes associated with arabinoxylan degradation, xylose metabolism, and short-chain fatty acid production. These data suggest xylanase elicits a stimbiotic MOA in the large intestine of pigs fed corn-based fiber.
Cyclic Conversions in the Nitrogen Cycle
Authors: Kleerebezem Robbert , Lücker Sebastian
Published: March 2021

The cyclic nature of specific conversions in the nitrogen cycle imposes strict limitations to the conversions observed in nature and explains for example why anaerobic ammonium oxidation (anammox) bacteria can only use nitrite – and not nitrate – as electron acceptor in catabolism, and why nitrite is required as additional electron donor for inorganic carbon fixation in anabolism. Furthermore, the biochemistry involved in nitrite-dependent anaerobic methane oxidation excludes the feasibility of using nitrate as electron acceptor. Based on the cyclic nature of these nitrogen conversions, we propose two scenarios that may explain the ecological role of recently discovered complete ammonia-oxidizing (comammox) Nitrospira spp., some of which were initially found in a strongly oxygen limited environment: (i) comammox Nitrospira spp. may actually catalyze an anammox-like metabolism using a biochemistry similar to intra-oxic nitrite-dependent methane oxidation, or (ii) scavenge all available oxygen for ammonia activation and use nitrate as terminal electron acceptor. Both scenarios require the presence of the biochemical machinery for ammonia oxidation to nitrate, potentially explaining a specific ecological niche for the occurrence of comammox bacteria in nature.
Genetic Polymorphism Drives Susceptibility Between Bacteria and Bacteriophages
Authors: Zhang Xiaoxu , Xiong Dongyan , Yu Junping , Yang Hang , He Ping , Wei Hongping
Published: March 2021

Phage therapy has attracted much attention for the treatment of antibiotic-resistant bacteria in recent years. However, it is common for bacteria to obtain resistance capability in short time after interaction with a lytic phage, as observed in phage therapy and co-culture of host and phage in a lab. In order to understand the mechanisms behind resistance, Staphylococcus aureus AB91118 and its lytic phage LQ7 were studied as a model system. A mutant strain named R1-3-1 resistant to the ancestral phage LQ7 was isolated, and then phages experimentally evolved from LQ7 were able to kill R1-3-1. Genomes of the two bacterial strains and the three phages (LQ7, ELQ7P-10, and ELQ7P-20) were analyzed based on deep sequencing data of NGS. Analyses showed that a few mutations could be identified in R1-3-1 and the evolved phages. Instead, in all the genomes of the bacteria and the phages, there exists genetic polymorphism of minor alleles, which distributes in many functional genes. Specifically, in the AB91118-LQ7 system it was found that the unique polymorphism sites in R1-3-1 associated to metabolic pathways could be inhibited by chloramphenicol (CHL). The resistant mutant R1-3-1 could become sensitive to the phage LQ7 in the presence of CHL. Combined use of CHL and the evolved phage from 20 cycles (ELQ7P-20) could produce the least resistance when killing the bacteria AB91118. The genetic polymorphism of minor alleles would be a new mechanism to drive the co-evolution between a phage and its host, which may enable the phage and the host get ready and fast response to the selective pressure from one to the other.
Isolation and Identification of Antibacterial Bioactive Compounds From Bacillus megaterium L2
Authors: Xie Yudan , Peng Qiuju , Ji Yuyu , Xie Ailin , Yang Long , Mu Shuzhen , Li Zhu , He Tengxia , Xiao Yang , Zhao Jinyi , Zhang Qinyu
Published: March 2021

Bacterial metabolites exhibit a variety of biologically active compounds including antibacterial and antifungal activities. It is well known that Bacillus is considered to be a promising source of bioactive secondary metabolites. Most plant pathogens have an incredible ability to mutate and acquire resistance, causing major economic losses in the agricultural field. Therefore, it is necessary to use the natural antibacterial compounds in microbes to control plant pathogens. This study was conducted to investigate the bio-active compounds of Bacillus megaterium L2. According to the activity guidance of Agrobacterium tumefaciens T-37, Erwinia carotovora EC-1 and Ralstonia solanacearum RS-2, five monomeric compounds, including erucamide (1), behenic acid (2), palmitic acid (3), phenylacetic acid (4), and β-sitosterol (5), were fractionated and purified from the crude ethyl acetate extract of B. megaterium. To our knowledge, all compounds were isolated from the bacterium for the first time. To understand the antimicrobial activity of these compounds, and their minimum inhibitory concentrations (MICs) (range: 0.98∼500 μg/mL) were determined by the broth microdilution method. For the three tested pathogens, palmitic acid exhibited almost no antibacterial activity (>500 μg/mL), while erucamide had moderate antibacterial activity (MIC = 500 μg/mL). Behenic acid showed MICs of 250 μg/mL against T-37 and RS-2 strains with an antibacterial activity. β-sitosterol showed significant antimicrobial activity against RS-2. β-sitosterol showed remarkable antimicrobial activity against RS-2 with an MIC of 15.6 μg/mL. In addition, with the antimicrobial activity, against T-37 (62.5 μg/mL) and against EC-1 (125 μg/mL) and RS-2 (15.6 μg/mL) strains notably, phenylacetic acid may be interesting for the prevention and control of phytopathogenic bacteria. Our findings suggest that isolated compounds such as behenic acid, β-sitosterol, and phenylacetic acid may be promising candidates for natural antimicrobial agents.
The Dual Regulation of Apoptosis by Flavivirus
Authors: Pan Yuhong , Cheng Anchun , Wang Mingshu , Yin Zhongqiong , Jia Renyong
Published: March 2021

Apoptosis is a form of programmed cell death, which maintains cellular homeostasis by eliminating pathogen-infected cells. It contains three signaling pathways: death receptor pathway, mitochondria-mediated pathway, and endoplasmic reticulum pathway. Its importance in host defenses is highlighted by the observation that many viruses evade, hinder or destroy apoptosis, thereby weakening the host’s immune response. Flaviviruses such as Dengue virus, Japanese encephalitis virus, and West Nile virus utilize various strategies to activate or inhibit cell apoptosis. This article reviews the research progress of apoptosis mechanism during flaviviruses infection, including flaviviruses proteins and subgenomic flaviviral RNA to regulate apoptosis by interacting with host proteins, as well as various signaling pathways involved in flaviviruses-induced apoptosis, which provides a scientific basis for understanding the pathogenesis of flaviviruses and helps in developing an effective antiviral therapy.
Self-reference Network-Related Interactions During the Process of Cognitive Impairment in the Early Stages of Alzheimer’s Disease
Authors: Wei Ping-Hsuan , Chen Haifeng , Ye Qing , Zhao Hui , Xu Yun , Bai Feng ,   on behalf of Alzheimer’s Disease Neuroimaging Initiative
Published: March 2021

Background: Normal establishment of cognition occurs after forming a sensation to stimuli from internal or external cues, in which self-reference processing may be partially involved. However, self-reference processing has been less studied in the Alzheimer’s disease (AD) field within the self-reference network (SRN) and has instead been investigated within the default-mode network (DMN). Differences between these networks have been proven in the last decade, while ultra-early diagnoses have increased. Therefore, investigation of the altered pattern of SRN is significantly important, especially in the early stages of AD.

Methods: A total of 65 individuals, including 43 with mild cognitive impairment (MCI) and 22 cognitively normal individuals, participated in this study. The SRN, dorsal attention network (DAN), and salience network (SN) were constructed with resting-state functional magnetic resonance imaging (fMRI), and voxel-based analysis of variance (ANOVA) was used to explore significant regions of network interactions. Finally, the correlation between the network interactions and clinical characteristics was analyzed.

Results: We discovered four interactions among the three networks, with the SRN showing different distributions in the left and right hemispheres from the DAN and SN and modulated interactions between them. Group differences in the interactions that were impaired in MCI patients indicated that the degree of damage was most severe in the SRN, least severe in the SN, and intermediate in the DAN. The two SRN-related interactions showed positive effects on the executive and memory performances of MCI patients with no overlap with the clinical assessments performed in this study.

Conclusion: This study is the first and primary evidence of SRN interactions related to MCI patients’ functional performance. The influence of the SRN in the ultra-early stages of AD is nonnegligible. There are still many unknowns regarding the contribution of the SRN in AD progression, and we strongly recommend future research in this area.
Mesenchymal Stem Cells Transplantation in Intracerebral Hemorrhage: Application and Challenges
Authors: Gong Yu-hua , Hao Shi-lei , Wang Bo-chu
Published: March 2021

Intracerebral hemorrhage (ICH) is one of the leading causes of death and long-term disability worldwide. Mesenchymal stem cell (MSC) therapies have demonstrated improved outcomes for treating ICH-induced neuronal defects, and the neural network reconstruction and neurological function recovery were enhanced in rodent ICH models through the mechanisms of neurogenesis, angiogenesis, anti-inflammation, and anti-apoptosis. However, many key issues associated with the survival, differentiation, and safety of grafted MSCs after ICH remain to be resolved, which hinder the clinical translation of MSC therapy. Herein, we reviewed an overview of the research status of MSC transplantation after ICH in different species including rodents, swine, monkey, and human, and the challenges for MSC-mediated ICH recovery from pathological microenvironment have been summarized. Furthermore, some efficient strategies for the outcome improvement of MSC transplantation were proposed.
Perampanel Improves Cortical Myoclonus and Disability in Progressive Myoclonic Epilepsies: A Case Series and a Systematic Review of the Literature
Authors: Assenza Giovanni , Nocerino Cristofaro , Tombini Mario , Di Gennaro Giancarlo , D'Aniello Alfredo , Verrotti Alberto , Marrelli Alfonso , Ricci Lorenzo , Lanzone Jacopo , Di Lazzaro Vincenzo , Bilo Leonilda , Coppola Antonietta
Published: March 2021

Introduction: Progressive myoclonic epilepsies (PMEs) are a heterogenous group of genetic diseases presenting with epilepsy, cognitive impairment, and severe action myoclonus, which can severely affect daily life activities and independent walking ability. Perampanel is a recent commercially available antiseizure medication with high efficacy against generalized seizures. Some reports supported the role of perampanel in ameliorating action myoclonus in PMEs. Here, we aimed to describe a case series and provide a systematic literature review on perampanel effects on PMEs.

Methods: We report the perampanel effectiveness on myoclonus, daily life activities, and seizures on an original Italian multicenter case series of 11 individuals with PMEs. Then, using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, we performed a systematic review on perampanel effect on myoclonus and disability in PMEs. We searched PubMed, Scopus, and Google Scholar articles on perampanel and PMEs up to June 2020. No prospective trials were found. We reviewed 11 case series manuscripts reporting 104 cases of different PMEs.

Results: Here, we are reporting the effectiveness of perampanel in five individuals affected by Unverricht–Lundborg disease, three by Lafora disease, two by sialidosis, and one by an undetermined PME. Nine out of 11 individuals improved their disability related to the action myoclonus (two with Lafora disease did not). Among the 104 persons with PMEs collected by the systematic review, we found that more than half of the patients receiving perampanel exhibited an amelioration of action myoclonus and, consequently, of their independence in daily life activities. The Unverricht–Lundborg disease seemed to show the best clinical response to perampanel, in comparison with the other more severe PMEs. A significant seizure reduction was achieved by almost all persons with active epilepsy. Only 11% of PME patients dropped out due to inefficacy.

Conclusions: Perampanel demonstrated a beneficial effect with regard to action myoclonus, disability, and seizures and was well-tolerated in people with PMEs, independently from their genetic diagnosis. Given the limited scientific evidence, broader prospective trials should be encouraged.
Protective Effects of Deferoxamine on Vestibulotoxicity in Gentamicin-Induced Bilateral Vestibulopathy Rat Model
Authors: Kim Hyo-Jung , Lee Jin-Ok , Kim Ji-Soo
Published: March 2021

Introduction: Administration of aminoglycoside (AG) antibiotics is one of the most common causes of ototoxicity. This study aimed to determine the protective effects of deferoxamine, an iron-chelating agent, on vestibulotoxicity using an intratympanic gentamicin injection (ITGM)-induced bilateral vestibulopathy rat model.

Methods: Fifteen Sprague-Dawley rats were randomly assigned to the ITGM only (n = 5), the ITGM combined with intramuscular deferoxamine (DFO) injection (ITGM+DFO, n = 5), or the intratympanic normal saline (control, n = 5) group. The rats in the ITGM+DFO group received intramuscular injection of 150 mg/kg of deferoxamine at 30, 90, and 150 min after the ITGM. The vestibular function was evaluated using the rotarod and open field test every 3 days after the injection until Day 16 when the rats were subjected to histological changes.

Results: The rats in the ITGM only group began to show significantly impaired vestibular function 2 days after ITGM into both ears. In contrast, the vestibular function was maintained in the control and ITGM+DFO groups without a difference throughout the experiments. The rats in the ITGM only group showed a near-complete loss of the type I and II hair cells and a collapse of the sensory epithelium in both the saccule and utricle. In contrast, the rats in the ITGM+DFO and control groups showed a relatively well-preserved sensory epithelium including the hair cells, cilia, and otolith layer.

Conclusion: This study provides experimental evidence for preventive effects of iron-chelating agents on AG-induced vestibulotoxicity. Simultaneous administration of iron-chelating agents may be considered when using ototoxic agents, especially in those considered to be vulnerable to toxic damage of the inner ear.