bluuebunny/crossref_metadata_2025 huggingface dataset:
Asperuloside Enhances Taste Perception and Prevents Weight Gain in High-Fat Fed Mice
Authors: Ishaq Muhammad , Tran Duyen , Wu Yijia , Nowak Krzysztof , Deans Bianca J. , Xin Joycelin Tan Zhu , Loh Hui Lin , Ng Wen Ying , Yee Chin Wen , Southam Benjamin , Vicenzi Silvia , Randall Cameron , Yang Cheng , Tan Ee , Pasupuleti Manideepika , Grewal Avneet Kaur , Ahmad Tauseef , Shastri Madhur , Vicario Carmelo , Ronci Maurizio , Zuccarini Mariachiara , Bleasel Martin , Scowen Paul , Raffaeli William , D’Andrea Gianvicenzo , Chellappan Dinesh Kumar , Jacobson Glenn , Bissember Alex C. , Smith Jason A. , Eri Raj , Canales Juan , Iglesias Miguel , Guven Nuri , Caruso Vanni
Published: April 2021

Asperuloside is an iridoid glycoside found in many medicinal plants that has produced promising anti-obesity results in animal models. In previous studies, three months of asperuloside administration reduced food intake, body weight, and adipose masses in rats consuming a high fat diet (HFD). However, the mechanisms by which asperuloside exerts its anti-obesity properties were not clarified. Here, we investigated homeostatic and nutrient-sensing mechanisms regulating food intake in mice consuming HFD. We confirmed the anti-obesity properties of asperuloside and, importantly, we identified some mechanisms that could be responsible for its therapeutic effect. Asperuloside reduced body weight and food intake in mice consuming HFD by 10.5 and 12.8% respectively, with no effect on mice eating a standard chow diet. Fasting glucose and plasma insulin were also significantly reduced. Mechanistically, asperuloside significantly reduced hypothalamic mRNA ghrelin, leptin, and pro-opiomelanocortin in mice consuming HFD. The expression of fat lingual receptors (CD36, FFAR1-4), CB1R and sweet lingual receptors (TAS1R2-3) was increased almost 2-fold by the administration of asperuloside. Our findings suggest that asperuloside might exert its therapeutic effects by altering nutrient-sensing receptors in the oral cavity as well as hypothalamic receptors involved in food intake when mice are exposed to obesogenic diets. This signaling pathway is known to influence the subtle hypothalamic equilibrium between energy homeostasis and reward-induced overeating responses. The present pre-clinical study demonstrated that targeting the gustatory system through asperuloside administration could represent a promising and effective new anti-obesity strategy.
Disrupted Lipid Metabolism in Multiple Sclerosis: A Role for Liver X Receptors?
Authors: Pineda-Torra Inés , Siddique Sherrice , Waddington Kirsty E. , Farrell Rachel , Jury Elizabeth C.
Published: April 2021

Multiple sclerosis (MS) is a chronic neurological disease driven by autoimmune, inflammatory and neurodegenerative processes leading to neuronal demyelination and subsequent degeneration. Systemic lipid metabolism is disturbed in people with MS, and lipid metabolic pathways are crucial to the protective process of remyelination. The lipid-activated transcription factors liver X receptors (LXRs) are important integrators of lipid metabolism and immunity. Consequently, there is a strong interest in targeting these receptors in a number of metabolic and inflammatory diseases, including MS. We have reviewed the evidence for involvement of LXR-driven lipid metabolism in the dysfunction of peripheral and brain-resident immune cells in MS, focusing on human studies, both the relapsing remitting and progressive phases of the disease are discussed. Finally, we discuss the therapeutic potential of modulating the activity of these receptors with existing pharmacological agents and highlight important areas of future research.
Sex Differences in Brown Adipose Tissue Function: Sex Hormones, Glucocorticoids, and Their Crosstalk
Authors: Kaikaew Kasiphak , Grefhorst Aldo , Visser Jenny A.
Published: April 2021

Excessive fat accumulation in the body causes overweight and obesity. To date, research has confirmed that there are two types of adipose tissue with opposing functions: lipid-storing white adipose tissue (WAT) and lipid-burning brown adipose tissue (BAT). After the rediscovery of the presence of metabolically active BAT in adults, BAT has received increasing attention especially since activation of BAT is considered a promising way to combat obesity and associated comorbidities. It has become clear that energy homeostasis differs between the sexes, which has a significant impact on the development of pathological conditions such as type 2 diabetes. Sex differences in BAT activity may contribute to this and, therefore, it is important to address the underlying mechanisms that contribute to sex differences in BAT activity. In this review, we discuss the role of sex hormones in the regulation of BAT activity under physiological and some pathological conditions. Given the increasing number of studies suggesting a crosstalk between sex hormones and the hypothalamic-pituitary-adrenal axis in metabolism, we also discuss this crosstalk in relation to sex differences in BAT activity.
The State of Migratory Landbirds in the East Asian Flyway: Distributions, Threats, and Conservation Needs
Authors: Yong Ding Li , Heim Wieland , Chowdhury Sayam U. , Choi Chang-Yong , Ktitorov Pavel , Kulikova Olga , Kondratyev Alexander , Round Philip D. , Allen Desmond , Trainor Colin R. , Gibson Luke , Szabo Judit K.
Published: April 2021

With nearly 400 migratory landbird species, the East Asian Flyway is the most diverse of the world’s flyways. This diversity is a consequence of the varied ecological niches provided by biomes ranging from broadleaf forests to arctic tundra and accentuated by complex biogeographic processes. The distribution and migration ecology of East Asian landbirds is still inadequately known, but a recent explosion in the number of studies tracking the migration of raptors, cuckoos, kingfishers and passerines has greatly increased our knowledge about the stopover and wintering ecology of many species, and the migratory routes that link northeast Eurasia and the Asian tropics. Yet the East Asian Flyway also supports the highest number of threatened species among flyways. Strong declines have been detected in buntings (Emberizidae) and other long-distance migrants. While the conservation of migratory landbirds in this region has largely focused on unsustainable hunting, there are other threats, such as habitat loss and increased agro-chemical use driven directly by land cover change and climate-related processes. Important knowledge gaps to be addressed include (1) threats affecting species in different parts of their annual cycle, (2) range-wide population trends, (3) ecological requirements and habitat use during the non-breeding season, and (4) the conservation status of critical wintering sites (including understudied farming landscapes, such as rice fields) and migration bottlenecks along the flyway.
Hijacking Transposable Elements for Saturation Mutagenesis in Fungi
Authors: Schrevens Sanne , Sanglard Dominique
Published: April 2021

Transposable elements are present in almost all known genomes, these endogenous transposons have recently been referred to as the mobilome. They are now increasingly used in research in order to make extensive mutant libraries in different organisms. Fungi are an essential part of our lives on earth, they influence the availability of our food and they live inside our own bodies both as commensals and pathogenic organisms. Only few fungal species have been studied extensively, mainly due to the lack of appropriate molecular genetic tools. The use of transposon insertion libraries can however help to rapidly advance our knowledge of (conditional) essential genes, compensatory mutations and drug target identification in fungi. Here we give an overview of some recent developments in the use of different transposons for saturation mutagenesis in different fungi.
CBA: Cluster-Guided Batch Alignment for Single Cell RNA-seq
Authors: Yu Wenbo , Mahfouz Ahmed , Reinders Marcel J. T.
Published: April 2021

The power of single-cell RNA sequencing (scRNA-seq) in detecting cell heterogeneity or developmental process is becoming more and more evident every day. The granularity of this knowledge is further propelled when combining two batches of scRNA-seq into a single large dataset. This strategy is however hampered by technical differences between these batches. Typically, these batch effects are resolved by matching similar cells across the different batches. Current approaches, however, do not take into account that we can constrain this matching further as cells can also be matched on their cell type identity. We use an auto-encoder to embed two batches in the same space such that cells are matched. To accomplish this, we use a loss function that preserves: (1) cell-cell distances within each of the two batches, as well as (2) cell-cell distances between two batches when the cells are of the same cell-type. The cell-type guidance is unsupervised, i.e., a cell-type is defined as a cluster in the original batch. We evaluated the performance of our cluster-guided batch alignment (CBA) using pancreas and mouse cell atlas datasets, against six state-of-the-art single cell alignment methods: Seurat v3, BBKNN, Scanorama, Harmony, LIGER, and BERMUDA. Compared to other approaches, CBA preserves the cluster separation in the original datasets while still being able to align the two datasets. We confirm that this separation is biologically meaningful by identifying relevant differential expression of genes for these preserved clusters.
Predicting Metabolite–Disease Associations Based on LightGBM Model
Authors: Zhang Cheng , Lei Xiujuan , Liu Lian
Published: April 2021

Metabolites have been shown to be closely related to the occurrence and development of many complex human diseases by a large number of biological experiments; investigating their correlation mechanisms is thus an important topic, which attracts many researchers. In this work, we propose a computational method named LGBMMDA, which is based on the Light Gradient Boosting Machine (LightGBM) to predict potential metabolite–disease associations. This method extracts the features from statistical measures, graph theoretical measures, and matrix factorization results, utilizing the principal component analysis (PCA) process to remove noise or redundancy. We evaluated our method compared with other used methods and demonstrated the better areas under the curve (AUCs) of LGBMMDA. Additionally, three case studies deeply confirmed that LGBMMDA has obvious superiority in predicting metabolite–disease pairs and represents a powerful bioinformatics tool.
Refugeeness, Sexuality, and Gender: Spatialized Lived Experiences of Intersectionality by Queer Asylum Seekers and Refugees in Paris
Authors: Chossière Florent
Published: April 2021

In the last few years, asylum claims based on sexual orientation and/or gender identity (SOGI) have received increased attention within migration and queer studies. Mostly focusing on the refugee status determination process, these works have emphasized how the expectations of asylum institutions about “genuine queer refugees” lead to the exclusion of many applicants from SOGI asylum. This paper aims at shifting the analysis perspective from the legal categorization process to the impacts of everyday experienced categories of “asylum seekers” or “refugees” on queer migrants in the Parisian area. Using a three-year long ethnographic fieldwork, completed through interviews with queer asylum seekers and refugees, this paper investigates how refugeeness, understood as the objective and subjective effects of migration and asylum policies on individuals, contributes to shaping lived experiences of sexual and gender minorities in France. By drawing attention to the ways that the multiple power relationships queer asylum seekers and refugees have to face are spatially grounded, this paper discusses how an intersectional understanding of sexuality, gender, and refugeeness allows us to emphasize the role played by migration status in the negotiation of hetero- and cisnormativity. This paper also argues that far from remaining passive toward the categorization process they are subjected to, queer asylum seekers and refugees strategically appropriate the administrative categories with which they are associated. Such an analysis of lived experiences of queer asylum seekers and refugees in the country of arrival thus highlights the complex reshaping of social location caused by migration.
Erythropoietin Promotes Infection Resolution and Lowers Antibiotic Requirements in E. coli- and S. aureus-Initiated Infections
Authors: Liang Feihong , Guan Huiting , Li Wenhua , Zhang Xue , Liu Tingting , Liu Yu , Mei Jie , Jiang Cheng , Zhang Fengxue , Luo Bangwei , Zhang Zhiren
Published: April 2021

Endogenous mechanisms underlying bacterial infection resolution are essential for the development of novel therapies for the treatment of inflammation caused by infection without unwanted side effects. Herein, we found that erythropoietin (EPO) promoted the resolution and enhanced antibiotic actions in Escherichia coli (E. coli)- and Staphylococcus aureus (S. aureus)-initiated infections. Levels of peritoneal EPO and macrophage erythropoietin receptor (EPOR) were elevated in self-limited E. coli-initiated peritonitis. Myeloid-specific EPOR-deficient mice exhibited an impaired inflammatory resolution and exogenous EPO enhanced this resolution in self-limited infections. Mechanistically, EPO increased macrophage clearance of bacteria via peroxisome proliferator-activated receptor γ (PPARγ)-induced CD36. Moreover, EPO ameliorated inflammation and increased the actions of ciprofloxacin and vancomycin in resolution-delayed E. coli- and S. aureus-initiated infections. Collectively, macrophage EPO signaling is temporally induced during infections. EPO is anti-phlogistic, increases engulfment, promotes infection resolution, and lowers antibiotic requirements.
Effects of Cryopreservation on Gene Expression and Post Thaw Sperm Quality of Pacific Abalone, Haliotis discus hannai
Authors: Hossen Shaharior , Sukhan Zahid Parvez , Cho Yusin , Kho Kang Hee
Published: April 2021

Pacific abalone, Haliotis discus hannai, is a high commercial seafood in South-East Asia. The aim of the present study was to determine effects of cryopreservation on gene expression and post thaw sperm quality of Pacific abalone. Two ions, Na+ (459.1 ± 3.1 mM) and Cl– (515.9 ± 1.1 mM), were predominant in the seminal plasma (pH: 6.8 ± 0.1; osmolarity: 1,126 ± 3 mOsmL–1). Cryopreservation reduced mRNA expression levels of protein kinase A (PKA-C) and heat shock proteins (HSP70 and HSP90) genes in sperm. Fluorescent technique was used to compare morphological defects, acrosome integrity (AI), plasma membrane integrity (PMI), mitochondrial membrane potential (MMP), and DNA integrity of sperm cryopreserved with five different cryopreservation solutions (8% Me2SO, 8% EG, 6% PG, 2% GLY, and 2% MeOH). Droplet in tail and coiled tail defects was not observed for sperm cryopreserved with 8% Me2SO or 2% GLY. Sperm cryopreserved with 8% Me2SO showed improved DNA integrity and lower cryodamage than sperm cryopreserved with other cryoprotectants. Sperm to egg ratio of 10,000:1 was found to be the most suitable ratio for in vitro fertilization among different ratios tested. The fertilization rate of sperm cryopreserved with 8% Me2SO was not significantly (p > 0.05) different from that of sperm cryopreserved with 2% GLY. DNA fragmentation showed strongly negative relationships with sperm quality parameters. Sperm cryopreserved with 8% Me2SO showed higher post thaw quality and mRNA expression of sperm motility associated gene than those cryopreserved with other cryoprotectants. The present research suggests to use 8% Me2SO for cryopreservation of Pacific abalone sperm as well as for hatchery production.
Numerical Study on Confinement Effect and Efficiency of Concentrically Loaded RACFRST Stub Columns
Authors: Liu Yicen , Lyu Fei , Ding Faxing , Wang En , Xu Yunlong , Yuan Tao , Deng Chao , Luo Chen
Published: April 2021

The mechanical behaviors of recycled aggregate concrete (RAC) are upgraded by outer steel tube confinement, and the performance of recycled aggregate concrete-filled steel tubular (RACFST) columns is similar to that of the traditional concrete-filled steel tube (CFST) columns. The purpose of this study is to investigate the behaviors of recycled aggregate concrete-filled rectangular steel tubular (RACFRST) stub columns under axial loading. Three-dimensional finite element (FE) models were established, which utilized a triaxial plastic-damage constitutive RAC model considering the replacement ratio of recycled aggregates. The finite element analysis results indicated that the lessened ultimate bearing capacity of RACFRST stub columns compared with their traditional concrete infilled counterparts was mainly due to the weakened confinement effect and confinement efficiency. A simplified formula of the bearing capacity of concentrically loaded RACFRST stub columns was proposed. The cross-sectional stress nephogram was reasonably simplified by the limited state of infilled concrete. The basics of proposed formula were the equilibrium condition and the superposition method. Finally, the formula for the bearing capacity of RACFRST stub columns was evaluated by comparing its accuracy and feasibility to some design formulae proposed by specialists and some design codes of different regions.
Erythropoietin Attenuates Experimental Contrast-Induced Nephrology: A Role for the Janus Kinase 2/Signal Transducer and Activator of Transcription 3 Signaling Pathway
Authors: Yang Jia , Zhou Jiaojiao , Wang Xin , Ji Ling , Wang Siwen , Chen Xuelian , Yang Lichuan
Published: April 2021

The aim of the present study was to investigate the effect of erythropoietin (EPO) on contrast-induced nephrology (CIN) in vivo and in vitro. Male C57BL/6J mice were divided into four groups: control, CIN (iohexol 6.0 g/kg), EPO (3,000 IU/kg), and CIN+EPO. Hematoxylin and eosin (H&E) staining and biochemical index analyses were performed to evaluate renal injury. The cellular proliferation rate was detected using the Cell Counting Kit-8 (CCK-8) assay. In addition, a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and flow cytometric assay were used to assess the apoptosis of tissue and cells, respectively. Renal protein expression associated with apoptosis, pyroptosis, and signaling pathways was determined by Western blot (WB) assays for tissues and cells. The results showed that EPO significantly decreased serum creatinine, blood urea nitrogen, and cystatin C levels and alleviated renal histological changes in vivo. The protein levels of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway components were overexpressed in the EPO treatment group. Furthermore, EPO suppressed the cell apoptosis and pyroptosis; decreased the protein levels of cleaved caspase-3, Bax, gasdermin D (GSDMD), and caspase-1; and enhanced the expression of Bcl-2. In summary, EPO could exert renoprotective effect by activating the JAK2/STAT3 signaling pathway, which may be a novel potential therapy for the treatment of CIN in the clinic.
Microbial Genomics as a Catalyst for Targeted Antivirulence Therapeutics
Authors: Sintchenko Vitali , Timms Verlaine , Sim Eby , Rockett Rebecca , Bachmann Nathan , O'Sullivan Matthew , Marais Ben
Published: April 2021

Virulence arresting drugs (VAD) are an expanding class of antimicrobial treatment that act to “disarm” rather than kill bacteria. Despite an increasing number of VAD being registered for clinical use, uptake is hampered by the lack of methods that can identify patients who are most likely to benefit from these new agents. The application of pathogen genomics can facilitate the rational utilization of advanced therapeutics for infectious diseases. The development of genomic assessment of VAD targets is essential to support the early stages of VAD diffusion into infectious disease management. Genomic identification and characterization of VAD targets in clinical isolates can augment antimicrobial stewardship and pharmacovigilance. Personalized genomics guided use of VAD will provide crucial policy guidance to regulating agencies, assist hospitals to optimize the use of these expensive medicines and create market opportunities for biotech companies and diagnostic laboratories.
Computational Simulation of Exosome Transport in Tumor Microenvironment
Authors: Koomullil Roy , Tehrani Behnam , Goliwas Kayla , Wang Yong , Ponnazhagan Selvarangan , Berry Joel , Deshane Jessy
Published: April 2021

Cellular exosome-mediated crosstalk in tumor microenvironment (TME) is a critical component of anti-tumor immune responses. In addition to particle size, exosome transport and uptake by target cells is influenced by physical and physiological factors, including interstitial fluid pressure, and exosome concentration. These variables differ under both normal and pathological conditions, including cancer. The transport of exosomes in TME is governed by interstitial flow and diffusion. Based on these determinants, mathematical models were adapted to simulate the transport of exosomes in the TME with specified exosome release rates from the tumor cells. In this study, the significance of spatial relationship in exosome-mediated intercellular communication was established by treating their movement in the TME as a continuum using a transport equation, with advection due to interstitial flow and diffusion due to concentration gradients. To quantify the rate of release of exosomes by biomechanical forces acting on the tumor cells, we used a transwell platform with confluent triple negative breast cancer cells 4T1.2 seeded in BioFlex plates exposed to an oscillatory force. Exosome release rates were quantified from 4T1.2 cells seeded at the bottom of the well following the application of either no force or an oscillatory force, and these rates were used to model exosome transport in the transwell. The simulations predicted that a larger number of exosomes reached the membrane of the transwell for 4T1.2 cells exposed to the oscillatory force when compared to controls. Additionally, we simulated the interstitial fluid flow and exosome transport in a 2-dimensional TME with macrophages, T cells, and mixtures of these two populations at two different stages of a tumor growth. Computational simulations were carried out using the commercial computational simulation package, ANSYS/Fluent. The results of this study indicated higher exosome concentrations and larger interstitial fluid pressure at the later stages of the tumor growth. Quantifying the release of exosomes by cancer cells, their transport through the TME, and their concentration in TME will afford a deeper understanding of the mechanisms of these interactions and aid in deriving predictive models for therapeutic intervention.
Intratracheal Poly(I:C) Exposure Accelerates the Immunological Disorder of Salivary Glands in Sjogren's-Like NOD/ShiLtJ Mice
Authors: Hu Peng , Ming Bingxia , Wu Xuefen , Cai Shaozhe , Tang Jungen , Dong Yuanji , Zhou Tianshu , Tan Zheng , Zhong Jixin , Zheng Fang , Dong Lingli
Published: April 2021

Evidences have suggested that Sjogren's syndrome (SS) is associated with viral infection. The aim of this study was to investigate the involvement of respiratory viral poly(I:C) in the pathogenesis of SS and potential mechanisms using a SS-like NOD/ShiLtJ (NOD) mouse model. 5-week female NOD mice were intratracheally administered poly(I:C) every other day for 5 times to mimic viral infection. Pilocarpine induced saliva secretion was determined every 8 days. Submandibular glands (SMG) and lungs were harvested for the detection of pathological changes. We found that intratracheal administration of poly(I:C) significantly advanced and enhanced the reduction of saliva flow rate in NOD mice. Furthermore, poly(I:C) treatment aggravated the histopathological lesions and inflammatory cells infiltration in SMG. Accompanied by elevated expression of IFN cytokines and IL-33, Th1 activation was enhanced in SMG of poly(I:C)-treated NOD mice, but Th17 cells activation was unchanged among the groups. In addition, intratracheal poly(I:C) exposure promoted the expression of IL-33 and increased T cells proportion in the lung, which were consistent with the change in SMG. Therefore, intratracheal poly(I:C) exposure aggravated the immunological and function disorder of SMG in NOD mice.
Targeting Antisense lncRNA PRKAG2-AS1, as a Therapeutic Target, Suppresses Malignant Behaviors of Hepatocellular Carcinoma Cells
Authors: Ou Yanjiao , Deng Yong , Wang Hong , Zhang Qingyi , Luo Huan , Hu Peng
Published: April 2021

Objective: Increasing evidence highlights antisense long non-coding RNAs (lncRNAs) as promising therapeutic targets for cancers. Herein, this study focused on the clinical implications and functions of a novel antisense lncRNA PRKAG2-AS1 in hepatocellular carcinoma (HCC).

Methods: PRKAG2-AS1 expression was examined in a cohort of 138 HCC patients by RT-qPCR. Overall survival (OS) and disease-free survival (DFS) analyses were presented based on PRKAG2-AS1 expression, followed by ROCs. After silencing PRKAG2-AS1, cell proliferation was assessed via CCK-8, colony formation and EdU staining assays. Migrated and invasive capacities were assessed by wound healing and transwell assays. The relationships between PRKAG2-AS1, miR-502-3p and BICD2 were validated by luciferase reporter, RIP and RNA pull-down assays. The expression and prognostic value of BICD2 were analyzed in TCGA database.

Results: PRKAG2-AS1 was up-regulated in HCC than normal tissue specimens. High PRKAG2-AS1 expression was indicative of poorer OS and DFS time. Area under the curves (AUCs) for OS and DFS were 0.8653 and 0.7891, suggesting the well predictive efficacy of PRKAG2-AS1 expression. Targeting PRKAG2-AS1 distinctly inhibited proliferation, migration, and invasion in HCC cells. PRKAG2-AS1 was mainly expressed in cytoplasm of HCC cells. PRKAG2-AS1 may directly bind to the sites of miR-502-3p. Up-regulation of BICD2 was found in HCC tissues and associated with unfavorable prognosis. BICD2 was confirmed to be a downstream target of miR-502-3p. PRKAG2-AS1 could regulate miR-502-3p/BICD2 axis.

Conclusion: Our findings identified a novel lncRNA PRKAG2-AS1 that was associated with clinical implications and malignant behaviors. Thus, PRKAG2-AS1 could become a promising therapeutic target.
Life in a Droplet: Microbial Ecology in Microscopic Surface Wetness
Authors: Orevi Tomer , Kashtan Nadav
Published: April 2021

While many natural and artificial surfaces may appear dry, they are in fact covered by thin liquid films and microdroplets invisible to the naked eye known as microscopic surface wetness (MSW). Central to the formation and the retention of MSW are the deliquescent properties of hygroscopic salts that prevent complete drying of wet surfaces or that drive the absorption of water until dissolution when the relative humidity is above a salt-specific level. As salts are ubiquitous, MSW occurs in many microbial habitats, such as soil, rocks, plant leaf, and root surfaces, the built environment, and human and animal skin. While key properties of MSW, including very high salinity and segregation into droplets, greatly affect microbial life therein, it has been scarcely studied, and systematic studies are only in their beginnings. Based on recent findings, we propose that the harsh micro-environment that MSW imposes, which is very different from bulk liquid, affects key aspects of bacterial ecology including survival traits, antibiotic response, competition, motility, communication, and exchange of genetic material. Further research is required to uncover the fundamental principles that govern microbial life and ecology in MSW. Such research will require multidisciplinary science cutting across biology, physics, and chemistry, while incorporating approaches from microbiology, genomics, microscopy, and computational modeling. The results of such research will be critical to understand microbial ecology in vast terrestrial habitats, affecting global biogeochemical cycles, as well as plant, animal, and human health.
Free Chlorine and Peroxynitrite Alter the Capsid Structure of Human Norovirus GII.4 and Its Capacity to Bind Histo-Blood Group Antigens
Authors: Chassaing Manon , Bastin Guillaume , Robin Maëlle , Majou Didier , Belliot Gaël , de Rougemont Alexis , Boudaud Nicolas , Gantzer Christophe
Published: April 2021

Human noroviruses (HuNoVs) are one of the leading causes of acute gastroenteritis worldwide. HuNoVs are frequently detected in water and foodstuffs. Free chlorine and peroxynitrite (ONOO−) are two oxidants commonly encountered by HuNoVs in humans or in the environment during their natural life cycle. In this study, we defined the effects of these two oxidants on GII.4 HuNoVs and GII.4 virus-like particles (VLPs). The impact on the capsid structure, the major capsid protein VP1 and the ability of the viral capsid to bind to histo-blood group antigens (HBGAs) following oxidative treatments were analyzed. HBGAs are attachment factors that promote HuNoV infection in human hosts. Overall, our results indicate that free chlorine acts on regions involved in the stabilization of VP1 dimers in VLPs and affects their ability to bind to HBGAs. These effects were confirmed in purified HuNoVs. Some VP1 cross-links also take place after free chlorine treatment, albeit to a lesser extent. Not only ONOO− mainly produced VP1 cross-links but can also dissociate VLPs depending on the concentration applied. Nevertheless, ONOO− has less effect on HuNoV particles.
High-Flow Nasal Cannula for COVID-19 Patients: A Multicenter Retrospective Study in China
Authors: Duan Jun , Zeng Jia , Deng Puyu , Ni Zhong , Lu Rongli , Xia Wenxi , Jing Guoqiang , Su Xiaoping , Ehrmann Stephan , Zhang Wei , Li Jie
Published: April 2021

Background: High-flow nasal cannula (HFNC) may help avoid intubation of hypoxemic patients suffering from COVID-19; however, it may also contribute to delaying intubation, which may increase mortality. Here, we aimed to identify the predictors of HFNC failure among patients with COVID-19.

Methods: We performed a multicenter retrospective study in China from January 15 to March 31, 2020. Two centers in Wuhan (resource-limited centers) enrolled 32 patients, and four centers outside Wuhan enrolled 34 cases. HFNC failure was defined as the requirement of escalation therapy (NIV or intubation). The ROX index (the ratio of SpO2/FiO2 to the respiratory rate) was calculated.

Results: Among the 66 patients, 29 (44%) cases experienced HFNC failure. The ROX index was much lower in failing patients than in successful ones after 1, 2, 4, 8, 12, and 24 h of HFNC. The ROX index was independently associated with HFNC failure (OR = 0.65; 95% CI: 0.45–0.94) among the variables collected before and 1 h after HFNC. To predict HFNC failure tested by ROX index, the AUC was between 0.73 and 0.79 for the time points of measurement 1–24 h after HFNC initiation. The HFNC failure rate was not different between patients in and outside Wuhan (41% vs. 47%, p = 0.63). However, the time from HFNC initiation to intubation was longer in Wuhan than that outside Wuhan (median 63 vs. 22 h, p = 0.02). Four patients in Wuhan underwent intubation due to cardiac arrest; in contrast, none of the patients outside Wuhan received intubation (13 vs. 0%, p = 0.05). The mortality was higher in Wuhan than that out of Wuhan, but the difference did not reach statistical significance (31 vs. 12%, p = 0.07).

Conclusion: The ROX index can be used to predict HFNC failure among COVID-19 patients to avoid delayed intubation, which may occur in the resource-limited area.
Methionine Redox Homeostasis in Protein Quality Control
Authors: Aussel Laurent , Ezraty Benjamin
Published: April 2021

Bacteria live in different environments and are subject to a wide variety of fluctuating conditions. During evolution, they acquired sophisticated systems dedicated to maintaining protein structure and function, especially during oxidative stress. Under such conditions, methionine residues are converted into methionine sulfoxide (Met-O) which can alter protein function. In this review, we focus on the role in protein quality control of methionine sulfoxide reductases (Msr) which repair oxidatively protein-bound Met-O. We discuss our current understanding of the importance of Msr systems in rescuing protein function under oxidative stress and their ability to work in coordination with chaperone networks. Moreover, we highlight that bacterial chaperones, like GroEL or SurA, are also targeted by oxidative stress and under the surveillance of Msr. Therefore, integration of methionine redox homeostasis in protein quality control during oxidative stress gives a complete picture of this bacterial adaptive mechanism.
Phenotyping Neuropsychiatric Symptoms Profiles of Alzheimer’s Disease Using Cluster Analysis on EEG Power
Authors: Liu Friedrich , Fuh Jong-Ling , Peng Chung-Kang , Yang Albert C.
Published: April 2021

Background: There has been an increasing interest in studying electroencephalogram (EEG) as a biomarker of Alzheimer’s disease but the association between EEG signals and patients’ neuropsychiatric symptoms remains unclear. We studied EEG signals of patients with Alzheimer’s disease to explore the associations between patients’ neuropsychiatric symptoms and clusters of patients based on their EEG powers.

Methods: A total of 69 patients with mild Alzheimer’s disease (the Clinical Dementia Rating = 1) were enrolled and their EEG signals from 19 channels/electrodes were recorded in three sessions for each patient. The EEG power was calculated by Fourier transform for the four frequency bands (beta: 13–40 Hz, alpha: 8–13 Hz, theta: 4–8 Hz, and delta: <4 Hz). We performed K-means cluster analysis to classify the 69 patients into two distinct groups by the log-transformed EEG powers (4 frequency bands × 19 channels) for the three EEG sessions. In each session, both clusters were compared with each other to assess the differences in their behavioral/psychological symptoms in terms of the Neuropsychiatric Inventory (NPI) score.

Results: While EEG band powers were highly consistent across all three sessions before clustering, EEG band powers were different between the two clusters in each session, especially for the delta waves. The delta band powers differed significantly between the two clusters in most channels across the three sessions. Patients’ demographics and cognitive function were not different between both clusters. However, their behavioral/psychological symptoms were different between the two clusters classified based on EEG powers. A higher NPI score was associated with the clustering of higher EEG powers.

Conclusion: The present study suggests that EEG power correlates to behavioral and psychological symptoms among patients with mild Alzheimer’s disease. The clustering approach of EEG signals may provide a novel and cost-effective method to differentiate the severity of neuropsychiatric symptoms and/or predict the prognosis for Alzheimer’s patients.
Predicting Dementia With Prefrontal Electroencephalography and Event-Related Potential
Authors: Doan Dieu Ni Thi , Ku Boncho , Choi Jungmi , Oh Miae , Kim Kahye , Cha Wonseok , Kim Jaeuk U.
Published: April 2021

Objective: To examine whether prefrontal electroencephalography (EEG) can be used for screening dementia.

Methods: We estimated the global cognitive decline using the results of Mini-Mental Status Examination (MMSE), measurements of brain activity from resting-state EEG, responses elicited by auditory stimulation [sensory event-related potential (ERP)], and selective attention tasks (selective-attention ERP) from 122 elderly participants (dementia, 35; control, 87). We investigated that the association between MMSE and each EEG/ERP variable by using Pearson’s correlation coefficient and performing univariate linear regression analysis. Kernel density estimation was used to examine the distribution of each EEG/ERP variable in the dementia and non-dementia groups. Both Univariate and multiple logistic regression analyses with the estimated odds ratios were conducted to assess the associations between the EEG/ERP variables and dementia prevalence. To develop the predictive models, five-fold cross-validation was applied to multiple classification algorithms.

Results: Most prefrontal EEG/ERP variables, previously known to be associated with cognitive decline, show correlations with the MMSE score (strongest correlation has |r| = 0.68). Although variables such as the frontal asymmetry of the resting-state EEG are not well correlated with the MMSE score, they indicate risk factors for dementia. The selective-attention ERP and resting-state EEG variables outperform the MMSE scores in dementia prediction (areas under the receiver operating characteristic curve of 0.891, 0.824, and 0.803, respectively). In addition, combining EEG/ERP variables and MMSE scores improves the model predictive performance, whereas adding demographic risk factors do not improve the prediction accuracy.

Conclusion: Prefrontal EEG markers outperform MMSE scores in predicting dementia, and additional prediction accuracy is expected when combining them with MMSE scores.

Significance: Prefrontal EEG is effective for screening dementia when used independently or in combination with MMSE.
Importance of Standards in Biomedical Device and Its Role in Strengthening the Healthcare Sector
Authors: Sumana Gajjala , Rajesh  , Aswal D. K.
Published: April 2021

Biomedical Metrology group of CSIR-NPL (Council of Scientific and Industrial Research—National Physical Laboratory), India is contributing significantly for establishing National Biomedical equipment standardswhich are traceable to primary standards to cater the quality control regulation in Health sector. This initiative has great impact on the health policy and Nation's economy as well. The laboratory has recently established biomedical equipment standard facility and disseminated the services to Industries, stake holders, hospitals and accredited laboratories. Although, the laboratory is successfully providing biomedical equipment calibration services for last 2 years, the sensitization of the information on the recently established metrological capabilities is required, which has great implications in implementation of India's New medical Device rule 2017 effectively. The present paper describes the summary on the significant achievements and role of National Physical Laboratory in supporting the Indian medical device regulations.
Ultraviolet-Filtering Luminescent Transparent Coatings for High-Performance PTB7-Th:ITIC–Based Organic Solar Cells
Authors: Farinhas Joana , Correia Sandra F. H. , Fu Lianshe , Botas Alexandre M. P. , André Paulo S. , Ferreira Rute A. S. , Charas Ana
Published: April 2021

Photovoltaic (PV) devices based on organic heterojunctions have recently achieved remarkable power conversion efficiency (PCE) values. However, photodegradation is often a cause of dramatic drops in device performance. The use of ultraviolet (UV)-absorbing luminescent downshifting (LDS) layers can be a mitigation strategy to simultaneously filter UV radiation reaching the device and reemit it with lower energy in the visible spectral range, matching the maximum spectral response of the PV cells and thus enabling the increase of the photocurrent generated by the cell. In this work, we report the use of a Eu3+-doped siliceous-based organic–inorganic hybrid as a coating on organic solar cells based on the PTB7-Th:ITIC bulk heterojunction with the purpose of increasing their performance. We found that the applied coatings yield a PCE enhancement of ∼22% (from 3.1 to 3.8%) in solar cells with spin-coated layers, compared with the bare solar cells, which is among the highest performance enhancements induced by plastic luminescent coatings.
Regulation of Glutamate, GABA and Dopamine Transporter Uptake, Surface Mobility and Expression
Authors: Ryan Renae M. , Ingram Susan L. , Scimemi Annalisa
Published: April 2021

Neurotransmitter transporters limit spillover between synapses and maintain the extracellular neurotransmitter concentration at low yet physiologically meaningful levels. They also exert a key role in providing precursors for neurotransmitter biosynthesis. In many cases, neurons and astrocytes contain a large intracellular pool of transporters that can be redistributed and stabilized in the plasma membrane following activation of different signaling pathways. This means that the uptake capacity of the brain neuropil for different neurotransmitters can be dynamically regulated over the course of minutes, as an indirect consequence of changes in neuronal activity, blood flow, cell-to-cell interactions, etc. Here we discuss recent advances in the mechanisms that control the cell membrane trafficking and biophysical properties of transporters for the excitatory, inhibitory and modulatory neurotransmitters glutamate, GABA, and dopamine.
A Perspective on Accelerated Aging Caused by the Genetic Deficiency of the Metabolic Protein, OPA1
Authors: Erchova Irina , Sun Shanshan , Votruba Marcela
Published: April 2021

Autosomal Dominant Optic Atrophy (ADOA) is an ophthalmological condition associated primarily with mutations in the OPA1 gene. It has variable onset, sometimes juvenile, but in other patients, the disease does not manifest until adult middle age despite the presence of a pathological mutation. Thus, individuals carrying mutations are considered healthy before the onset of clinical symptoms. Our research, nonetheless, indicates that on the cellular level pathology is evident from birth and mutant cells are different from controls. We argue that the adaptation and early recruitment of cytoprotective responses allows normal development and functioning but leads to an exhaustion of cellular reserves, leading to premature cellular aging, especially in neurons and skeletal muscle cells. The appearance of clinical symptoms, thus, indicates the overwhelming of natural cellular defenses and break-down of native protective mechanisms.
Bipolar Disorder and Parkinson's Disease: A 123I-Ioflupane Dopamine Transporter SPECT Study
Authors: Erro Roberto , Landolfi Annamaria , D'Agostino Giulia , Pace Leonardo , Picillo Marina , Scarano Massimo , Cuocolo Alberto , Pappatá Sabina , Vitale Carmine , Pellecchia Maria Teresa , Monteleone Palmiero , Barone Paolo
Published: April 2021

Objectives: Bipolar disorder (BD) has been suggested to be a risk factor for the development of Parkinson's disease (PD). Standard treatment of BD includes drugs that are known to induce drug-induced parkinsonism (DIP). Clinical differentiation between PD and DIP is crucial and might be aided by functional neuroimaging of the dopaminergic nigrostriatal pathway.

Methods: Twenty consecutive BD patients with parkinsonism were clinically assessed and underwent 123I-ioflupane dopamine transporter single-photon emission computer tomography (SPECT). Imaging data of BD patients with pathological scans were further compared to a population of 40 de novo PD patients.

Results: Four BD patients had abnormal scans, but their clinical features and cumulative exposure to both antipsychotic drugs and lithium were similar to those of BD patients with normal dopamine transporter imaging. BD patients with pathological scans had putaminal binding ratio and putamen-to-caudate ratios higher than those of PD patients despite a similar motor symptom burden.

Conclusions: Up to 20% of BD patients with parkinsonism might have an underlying dopaminergic deficit, which would not be due to cumulative exposure to offending drugs and is ostensibly higher than expected in the general population. This supports the evidence that BD represents a risk factor for subsequent development of neurodegenerative parkinsonism, the nature of which needs to be elucidated.
Factors Influencing the Severity and Progression of Respiratory Muscle Dysfunction in Myotonic Dystrophy Type 1
Authors: Hartog Leigh , Zhao Jing , Reynolds Jerry , Brokamp Gabrielle , Vilson Ferdinand , Arnold W. David , LoRusso Samantha
Published: April 2021

Respiratory complications are the most common cause of death among patients with Myotonic Dystrophy type 1 (DM1), but the natural history of respiratory decline in DM1 patients is incompletely characterized and few predictors of the progression of respiratory dysfunction have been identified. To identify factors influencing the progression of respiratory dysfunction electronic medical records from 110 adult patients diagnosed with DM1 were reviewed along with data for respiratory symptoms and pulmonary function obtained from routine respiratory therapist clinical evaluations. At baseline, 70.9% had evidence of restrictive respiratory impairment. We examined various parameters of respiratory functional status, and found FVC (% predicted) correlated best with other measures of disease severity. Annual change in FVC was −1.42 (std error = 0.381). Greater CTG repeat size, higher MIRS rating, and longer disease duration were all correlated with lower baseline FVC but not with annual rate of change. Wide variability in clinical phenotype made determination of disease measures directly related to respiratory functional decline challenging.
Determinants of Sleepiness at Wheel and Missing Accidents in Patients With Obstructive Sleep Apnea
Authors: Fanfulla Francesco , Pinna Gian Domenico , Marrone Oreste , D’Artavilla Lupo Nadia , Arcovio Simona , Bonsignore Maria R. , Morrone Elisa
Published: April 2021

Study Objectives

Motor-vehicle crashes are frequent in untreated OSA patients but there is still uncertainty on prevalence as well as physiological or clinical determinants of sleepiness at the wheel (SW) in OSA patients. We assessed determinants of SW or sleepiness related near-miss car accident (NMA) in a group of non-professional drivers with OSA.

Methods

A 237 consecutive, treatment-naïve PSG-diagnosed OSA patients (161 males, 53.1 ± 12.6 years) were enrolled. Self-reported SW was assessed by positive answer to the question, “Have you had episodes of falling asleep while driving or episodes of drowsiness at wheel that could interfere with your driving skill in the last year?” Occurrence of NMA in the last 3 years was also individually recorded. Habitual self-reported average sleep time was collected.

Results

SW was found in 41.3% of patients but one-quarter of patients with SW did not report excessive daytime sleepiness. Predictors of SW were the following subjective factors: Epworth sleepiness scale score (ESS-OR 1.26; IC 1.1–1.4; p < 0.0001), depressive symptoms (BDI-OR 1.2; IC 1.06–1.18; p < 0.0001) and level of risk exposure (annual mileage-OR 1.9; IC 1.15–3.1; p = 0.007). NMAs were reported by 9.7% of patients, but more frequently by SW+ than SW– (22.4% vs. 0.7%; χ2 31, p < 0.0001). The occurrence of NMAs was significantly associated to ESS, BDI, habitual sleep duration and ODI (R2 = 0.41).

Conclusion

SW is not predicted by severity of OSA. Evaluation of risk exposure, assessment of depressive symptoms, and reported NMA should be included in the clinical evaluation, particularly in patients with reduced habitual sleep time and severe nocturnal hypoxia.