bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-Dimensional Modeling of Thermal-Mechanical Behavior of Accident Tolerant Fuels
Authors: Zeng Zitao , Pan Yongyu , Chen Xi , Zhang Chunyu , Yin Chunyu , Gao Shixin , Zhou Yi , Zhang Jie , He Xiujie , Yuan Cenxi
Published: March 2021

Considering the safety issues of the traditional UO2-Zr fuel, a variety of accident-tolerant fuel (ATF) candidates have been proposed in recent years. Among the several ATFs, U3Si2, and UN are the two promising candidates for fuel materials owing to their high thermal conductivity and high uranium density. The FeCrAl alloy and the SiC/SiC composite material are the two promising candidates for cladding owing to their high oxidation resistance and high strength. In order to quantitatively evaluate the performance of ATFs, this study summarizes the physical models of typical ATF cladding materials (FeCrAl and SiC) and pellet materials (UN and U3Si2). Then a three-dimensional non-linear finite element method is applied to simulate the thermal-mechanical behavior of several typical fuel-cladding combinations, including UO2-FeCrAl, UN-FeCrAl, U3Si2-FeCrAl, U3Si2-Zr, and U3Si2-SiC. The important physical quantities, such as the fuel centerline temperature, the deformation of the pellet and the cladding as well as the pellet-cladding mechanical interaction (PCMI) were studied. The fission gas release model was also verified and improved.
False Data Injection Attack Detection in Power Systems Based on Cyber-Physical Attack Genes
Authors: Qu Zhaoyang , Dong Yunchang , Qu Nan , Li Huashun , Cui Mingshi , Bo Xiaoyong , Wu Yun , Mugemanyi Sylvère
Published: March 2021

In the process of the detection of a false data injection attack (FDIA) in power systems, there are problems of complex data features and low detection accuracy. From the perspective of the correlation and redundancy of the essential characteristics of the attack data, a detection method of the FDIA in smart grids based on cyber-physical genes is proposed. Firstly, the principle and characteristics of the FDIA are analyzed, and the concept of the cyber-physical FDIA gene is defined. Considering the non-functional dependency and nonlinear correlation of cyber-physical data in power systems, the optimal attack gene feature set of the maximum mutual information coefficient is selected. Secondly, an unsupervised pre-training encoder is set to extract the cyber-physical attack gene. Combined with the supervised fine-tuning classifier to train and update the network parameters, the FDIA detection model with stacked autoencoder network is constructed. Finally, a self-adaptive cuckoo search algorithm is designed to optimize the model parameters, and a novel attack detection method is proposed. The analysis of case studies shows that the proposed method can effectively improve the detection accuracy and effect of the FDIA on cyber-physical power systems.
Compared to Wildfire, Management Practices Reduced Old-Growth Forest Diversity and Functionality in Primary Boreal Landscapes of Eastern Canada
Authors: Martin Maxence , Grondin Pierre , Lambert Marie-Claude , Bergeron Yves , Morin Hubert
Published: March 2021

Large primary forest residuals can still be found in boreal landscapes. Their areas are however shrinking rapidly due to anthropogenic activities, in particular industrial-scale forestry. The impacts of logging activities on primary boreal forests may also strongly differ from those of wildfires, the dominant stand-replacing natural disturbance in these forests. Since industrial-scale forestry is driven by economic motives, there is a risk that stands of higher economic value will be primarily harvested, thus threatening habitats, and functions related to these forests. Hence, the objective of this study was to identify the main attributes differentiating burned and logged stands prior to disturbance in boreal forests. The study territory lies in the coniferous and closed-canopy boreal forest in Québec, Canada, where industrial-scale logging and wildfire are the two main stand-replacing disturbances. Based on Québec government inventories of primary forests, we identified 427 transects containing about 5.5 circular field plots/transect that were burned or logged shortly after being surveyed, between 1985 and 2016. Comparative analysis of the main structural and environmental attributes of these transects highlighted the strong divergence in the impact of fire and harvesting on primary boreal forests. Overall, logging activities mainly harvested forests with the highest economic value, while most burned stands were low to moderately productive or recently disturbed. These results raise concerns about the resistance and resilience of remnant primary forests within managed areas, particularly in a context of disturbance amplification due to climate change. Moreover, the majority of the stands studied were old-growth forests, characterized by a high ecological value but also highly threatened by anthropogenic disturbances. A loss in the diversity and functionality of primary forests, and particularly the old-growth forests, therefore adds to the current issues related to these ecosystems. Since 2013, the study area is under ecosystem-based management, which implies that there have been marked changes in forestry practices. Complementary research will be necessary to assess the capacity of ecosystem-based management to address the challenges identified in our study.
Initial Insights Into the Genetic Epidemiology of SARS-CoV-2 Isolates From Kerala Suggest Local Spread From Limited Introductions
Authors: Radhakrishnan Chandni , Divakar Mohit Kumar , Jain Abhinav , Viswanathan Prasanth , Bhoyar Rahul C. , Jolly Bani , Imran Mohamed , Sharma Disha , Rophina Mercy , Ranjan Gyan , Sehgal Paras , Jose Beena Philomina , Raman Rajendran Vadukkoot , Kesavan Thulaseedharan Nallaveettil , George Kalpana , Mathew Sheela , Poovullathil Jayesh Kumar , Keeriyatt Govindan Sajeeth Kumar , Nair Priyanka Raveendranadhan , Vadekkandiyil Shameer , Gladson Vineeth , Mohan Midhun , Parambath Fairoz Cheriyalingal , Mangla Mohit , Shamnath Afra ,   Indian CoV2 Genomics & Genetic Epidemiology (IndiCovGEN) Consortium, Sivasubbu Sridhar , Scaria Vinod
Published: March 2021

Coronavirus disease 2019 (COVID-19) rapidly spread from a city in China to almost every country in the world, affecting millions of individuals. The rapid increase in the COVID-19 cases in the state of Kerala in India has necessitated the understanding of SARS-CoV-2 genetic epidemiology. We sequenced 200 samples from patients in Kerala using COVIDSeq protocol amplicon-based sequencing. The analysis identified 166 high-quality single-nucleotide variants encompassing four novel variants and 89 new variants in the Indian isolated SARS-CoV-2. Phylogenetic and haplotype analysis revealed that the virus was dominated by three distinct introductions followed by local spread suggesting recent outbreaks and that it belongs to the A2a clade. Further analysis of the functional variants revealed that two variants in the S gene associated with increased infectivity and five variants mapped in primer binding sites affect the efficacy of RT-PCR. To the best of our knowledge, this is the first and most comprehensive report of SARS-CoV-2 genetic epidemiology from Kerala.
Systematic Characterization of Expression Profiles and Prognostic Values of the Eight Subunits of the Chaperonin TRiC in Breast Cancer
Authors: Xu Wen-Xiu , Song Wei , Jiang Meng-Ping , Yang Su-Jin , Zhang Jian , Wang Dan-Dan , Tang Jin-Hai
Published: March 2021

Background

Chaperonin-containing TCP-1 (TRiC or CCT) was demonstrated to be involved in oncogenesis of cancers carcinogenesis and development of various malignancies. Increasing experimental evidence indicated that dysregulation of TRiC was implicated in the tumor progression of breast cancer (BCa). However, few definitive studies have addressed the diverse expression patterns and prognostic values of eight TRiC subunits. Thus, we aimed to investigate the clinical significance of TRiC subunit expression and prognostic values for their possible implications in diagnosis and treatment of BCa.

Methods

Based on updated public resources and comprehensive bioinformatics analysis, we used some online databases (e.g., UALCAN, GEPIA, cBioPortal, TIMER, BC-GenExMiner, metascape, and GeneMANIA) to comprehensively explore the expression levels and the prognostic effects of eight TRiC subunits in patients with BCa.

Results

The transcriptional levels of most subunits of the Chaperonin TRiC (CCT2, CCT3, CCT4, CCT5, CCT6A, and CCT7) were significantly elevated compared with normal breast tissues, whereas TCP1, CCT4, and CCT6B were lower in BCa tissues than in normal tissues. Besides, copy-number alterations (CNA) of eight TRiC subunits positively regulated their mRNA expressions. Furthermore, high mRNA expression of TCP1/CCT2/CCT4/CCT5/CCT6A/CCT7/CCT8 was significantly associated with poor overall survival (OS) in BCa patients. The eight subunits of the chaperonin TRiC was related to tumor purity and immune infiltration levels of BCa. Co-expression analysis showed CCT6B was negatively associated with other subunits of TRiC and other subunits of TRiC were positively correlated with each other. Additionally, TRiC and their interactive proteins were correlated with positive regulation of biological process, localization, and biological regulation.

Conclusion

This study systematically illustrated the expression profiles and distinct prognostic values of chaperonin TRiC in BCa, providing insights for further investigation of subunits of the chaperonin TRiC as novel therapeutic targets and potential prognostic biomarkers in BCa.
Human Aquaporins: Functional Diversity and Potential Roles in Infectious and Non-infectious Diseases
Authors: Azad Abul Kalam , Raihan Topu , Ahmed Jahed , Hakim Al , Emon Tanvir Hossain , Chowdhury Parveen Afroz
Published: March 2021

Aquaporins (AQPs) are integral membrane proteins and found in all living organisms from bacteria to human. AQPs mainly involved in the transmembrane diffusion of water as well as various small solutes in a bidirectional manner are widely distributed in various human tissues. Human contains 13 AQPs (AQP0–AQP12) which are divided into three sub-classes namely orthodox aquaporin (AQP0, 1, 2, 4, 5, 6, and 8), aquaglyceroporin (AQP3, 7, 9, and 10) and super or unorthodox aquaporin (AQP11 and 12) based on their pore selectivity. Human AQPs are functionally diverse, which are involved in wide variety of non-infectious diseases including cancer, renal dysfunction, neurological disorder, epilepsy, skin disease, metabolic syndrome, and even cardiac diseases. However, the association of AQPs with infectious diseases has not been fully evaluated. Several studies have unveiled that AQPs can be regulated by microbial and parasitic infections that suggest their involvement in microbial pathogenesis, inflammation-associated responses and AQP-mediated cell water homeostasis. This review mainly aims to shed light on the involvement of AQPs in infectious and non-infectious diseases and potential AQPs-target modulators. Furthermore, AQP structures, tissue-specific distributions and their physiological relevance, functional diversity and regulations have been discussed. Altogether, this review would be useful for further investigation of AQPs as a potential therapeutic target for treatment of infectious as well as non-infectious diseases.
Immune Checkpoint-Associated Locations of Diffuse Gliomas Comparing Pediatric With Adult Patients Based on Voxel-Wise Analysis
Authors: Zhang Li , Zhang Buyi , Dou Zhangqi , Wu Jiawei , Iranmanesh Yasaman , Jiang Biao , Sun Chongran , Zhang Jianmin
Published: March 2021

Objective: Pediatric diffuse gliomas (pDGs) are relatively rare and molecularly distinct from pediatric pilocytic astrocytoma and adult DGs. Immunotherapy is a promising therapeutic strategy, requiring a deep understanding of tumor immune profiles. The spatial locations of brain tumors might be related to the molecular profiles. We aimed to analyze the relationship between the immune checkpoint molecules with the locations of DGs comparing pediatric with adult patients.

Method: We studied 20 pDGs patients (age ≤ 21 years old), and 20 paired adult patients according to gender and histological types selected from 641 adult patients with DGs. Immune checkpoint molecules including B7-H3, CD47, and PD-L1, as well as tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs), were manifested by immunohistochemical staining. Expression difference analyses and Spearman's correlation were performed. MRI data were voxel-wise normalized, segmented, and analyzed by Fisher's exact test to construct the tumor frequency and p value heatmaps. Survival analyses were conducted by Log-rank tests.

Result: The median age of pediatric patients was 16 years. 55% and 30% of patients were WHO II and III grades, respectively. The left frontal lobe and right cerebellum were the statistically significant locations for pDGs, while the anterior horn of ventricles for adult DGs. A potential association between the expression of PD-L1 and TAMs was found in pDGs (p = 0.002, R = 0.670). The right posterior external capsule and the lateral side of the anterior horn of the left ventricle were predominant locations for the adult patients with high expression of B7-H3 and low expression of PD-L1 compared to pediatric ones, respectively. Pediatric patients showed significantly improved overall survival compared with adults. The prognostic roles of immune checkpoint molecules and TILs/TAMs were not significantly different between the two groups.

Conclusion: Immune checkpoint-associated locations of diffuse gliomas comparing pediatric with adult patients could be helpful for the immunotherapy decisions and design of clinical trials.
Antibodies Targeting the Transferrin Receptor 1 (TfR1) as Direct Anti-cancer Agents
Authors: Candelaria Pierre V. , Leoh Lai Sum , Penichet Manuel L. , Daniels-Wells Tracy R.
Published: March 2021

The transferrin receptor 1 (TfR1), also known as cluster of differentiation 71 (CD71), is a type II transmembrane glycoprotein that binds transferrin (Tf) and performs a critical role in cellular iron uptake through the interaction with iron-bound Tf. Iron is required for multiple cellular processes and is essential for DNA synthesis and, thus, cellular proliferation. Due to its central role in cancer cell pathology, malignant cells often overexpress TfR1 and this increased expression can be associated with poor prognosis in different types of cancer. The elevated levels of TfR1 expression on malignant cells, together with its extracellular accessibility, ability to internalize, and central role in cancer cell pathology make this receptor an attractive target for antibody-mediated therapy. The TfR1 can be targeted by antibodies for cancer therapy in two distinct ways: (1) indirectly through the use of antibodies conjugated to anti-cancer agents that are internalized by receptor-mediated endocytosis or (2) directly through the use of antibodies that disrupt the function of the receptor and/or induce Fc effector functions, such as antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), or complement-dependent cytotoxicity (CDC). Although TfR1 has been used extensively as a target for antibody-mediated cancer therapy over the years, interest continues to increase for both targeting the receptor for delivery purposes and for its use as direct anti-cancer agents. This review focuses on the developments in the use of antibodies targeting TfR1 as direct anti-tumor agents.
Mesenchymal Stromal Cell-Derived Extracellular Vesicles Regulate the Mitochondrial Metabolism via Transfer of miRNAs
Authors: Loussouarn Claire , Pers Yves-Marie , Bony Claire , Jorgensen Christian , Noël Danièle
Published: March 2021

Mesenchymal stromal cells (MSCs) are the most commonly tested adult progenitor cells in regenerative medicine. They stimulate tissue repair primarily through the secretion of immune-regulatory and pro-regenerative factors. There is increasing evidence that most of these factors are carried on extracellular vesicles (EVs) that are released by MSCs, either spontaneously or after activation. Exosomes and microvesicles are the most investigated types of EVs that act through uptake by target cells and cargo release inside the cytoplasm or through interactions with receptors expressed on target cells to stimulate downstream intracellular pathways. They convey different types of molecules, including proteins, lipids and acid nucleics among which, miRNAs are the most widely studied. The cargo of EVs can be impacted by the culture or environmental conditions that MSCs encounter and by changes in the energy metabolism that regulate the functional properties of MSCs. On the other hand, MSC-derived EVs are also reported to impact the metabolism of target cells. In the present review, we discuss the role of MSC-EVs in the regulation of the energy metabolism and oxidative stress of target cells and tissues with a focus on the role of miRNAs.
Interplay Between the Intestinal Microbiota and Acute Graft-Versus-Host Disease: Experimental Evidence and Clinical Significance
Authors: Hong Tao , Wang Rui , Wang Xiaoqi , Yang Shijie , Wang Weihao , Gao Qiangguo , Zhang Xi
Published: March 2021

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for many hematological disorders and autoimmune diseases, but acute graft-versus-host disease (aGVHD) has remained a major obstacle that limits allo-HSCT and exhibits a daunting mortality rate. The gastrointestinal system is among the most common sites affected by aGVHD. Experimental advances in the field of intestinal microbiota research enhanced our understanding - not only of the quantity and diversity of intestinal microbiota - but also their association with homeostasis of the immune system and disease pathogenesis, including that of aGVHD. Meanwhile, ever-growing clinical evidence suggest that the intestinal microbiota is dysregulated in patients who develop aGVHD and that the imbalance may affect clinical outcomes, indicating a potential predictive role for microbiota dysregulation in aGVHD severity and prognosis. The current animal and human studies investigating the intestinal microbiota in aGVHD and the understanding of the influence and management of the microbiota in the clinic are reviewed herein. Taken together, monitoring and remodeling the intestinal microecology following allo-HSCT may provide us with promising avenues for diagnosing, preventing or treating aGVHD in the clinic.
Monocytes From Patients With Macrophage Activation Syndrome and Secondary Hemophagocytic Lymphohistiocytosis Are Hyperresponsive to Interferon Gamma
Authors: Pascarella Antonia , Bracaglia Claudia , Caiello Ivan , Arduini Alessia , Moneta Gian Marco , Rossi Marianna Nicoletta , Matteo Valentina , Pardeo Manuela , De Benedetti Fabrizio , Prencipe Giusi
Published: March 2021

Objective

To investigate the activation of the IFNγ signaling pathway in monocytes of patients with secondary hemophagocytic lymphohistiocytosis (sHLH)/macrophage activation syndrome (MAS) and to evaluate whether levels of phosphorylated STAT1 represent a biomarker for the identification of patients at early stages of the disease.

Methods

Fresh whole blood samples from pediatric patients with active sHLH/MAS, not receiving (n=10) and receiving glucocorticoids (n=14) at time of sampling, were prospectively collected. As disease control groups, patients with active systemic juvenile idiopathic arthritis (sJIA) without MAS, patients with sHLH/MAS in remission and patients with other rheumatic diseases were also sampled. Whole blood cells were left unstimulated or stimulated with increasing concentrations of IFNγ for 10 minutes and the intracellular Tyrosine (701)-phosphorylated STAT1 (pSTAT1) levels were evaluated in monocytes by flow cytometry.

Results

Monocytes from untreated sHLH/MAS patients showed significantly higher basal levels of pSTAT1 compared to those observed in monocytes from glucocorticoid-treated sHLH/MAS patients and from all the other disease controls. In addition, a significant increase in responsiveness to IFNγ, as assessed by increased levels of pSTAT1 following ex vivo stimulation, was observed in monocytes from untreated sHLH/MAS patients. pSTAT1 levels in monocytes distinguished patients with sHLH/MAS not treated with glucocorticoids from patients with active sJIA or with other rheumatic diseases [AUC, 0.93; 95% confidence interval 0.85-1.00, p<0.001]. Statistically significant correlations between IFNG mRNA levels in whole blood cells, circulating IFNγ levels and pSTAT1 levels in sHLH/MAS monocytes were found.

Conclusion

Our data demonstrating higher basal levels of pSTAT1 as well as a hyperreactivity to IFNγ stimulation in monocytes from patients with sHLH/MAS point to perturbations in the activation of downstream IFNγ signaling pathway as a contributor to the hyperinflammation occurring in these patients. Finally, the observation that glucocorticoids affect pSTAT1 levels in vivo, makes it difficult to consider the measurement of pSTAT1 levels as a biomarker to identify patients at early stages of sHLH/MAS in clinical practice.
Case Report: Administration of Amniotic Fluid-Derived Nanoparticles in Three Severely Ill COVID-19 Patients
Authors: Mitrani Maria Ines , Bellio Michael A. , Sagel Anthony , Saylor Marie , Kapp William , VanOsdol Kathryn , Haskell Gwendolyn , Stewart Danique , Abdullah Zanub , Santos Ivan , Milberg Julian , Arango Alissa , Mitrani Albert , Shapiro George C.
Published: March 2021

Rationale/Objectives: A human coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak worldwide. There is an urgent need to develop new interventions to suppress the excessive immune response, protect alveolar function, and repair lung and systemic organ damage. Zofin (previously known as Organicell Flow) is a novel therapeutic that is derived from the soluble and nanoparticle fraction (extracellular vesicles and exosomes) of human amniotic fluid. Here within, we present the clinical outcomes after Zofin treatment in three critically ill patients suffering from severe, multi-organ complications induced by COVID-19 infection. All patients were diagnosed with COVID-19, developed respiratory failure, and were hospitalized for more than 40 days.

Methods: Zofin was administered to patients concurrently with ongoing medical care who were monitored for 28-days post-therapy. SOFA score assessment, chest X-rays, and inflammatory biomarker testing was performed.

Main Results: There were no adverse events associated with the therapy. The patients showed improvements in ICU clinical status and experienced respiratory improvements. Acute delirium experienced by patients completely resolved and inflammatory biomarkers improved.

Conclusions: Primary outcomes demonstrate the therapy was safe, accessible, and feasible. This is the first demonstration of human amniotic fluid-derived nanoparticles as a safe and potentially efficacious therapeutic treatment for respiratory failure induced by COVID-19 infection.
Detecting SARS-CoV-2 in the Breath of COVID-19 Patients
Authors: Li Xiaoguang , Li Jing , Ge Qinggang , Du Yuguang , Li Guoqiang , Li Wei , Zhang Tong , Tan Lei , Zhang Runqiang , Yuan Xiaoning , Zhang He , Zhang Chen , Liu Wenjun , Ding Wei , Sun Liang , Chen Ke , Wang Zhuo , Shen Ning , Lu Jun
Published: March 2021

In the COVID-19 outbreak year 2020, a consensus was reached on the fact that SARS-CoV-2 spreads through aerosols. However, finding an efficient method to detect viruses in aerosols to monitor the risk of similar infections and enact effective control remains a great challenge. Our study aimed to build a swirling aerosol collection (SAC) device to collect viral particles in exhaled breath and subsequently detect SARS-CoV-2 using reverse transcription polymerase chain reaction (RT-PCR). Laboratory tests of the SAC device using aerosolized SARS-CoV-2 pseudovirus indicated that the SAC device can produce a positive result in only 10 s, with a collection distance to the source of 10 cm in a biosafety chamber, when the release rate of the pseudovirus source was 1,000,000 copies/h. Subsequent clinical trials of the device showed three positives and 14 negatives out of 27 patients in agreement with pharyngeal swabs, and 10 patients obtained opposite results, while no positive results were found in a healthy control group (n = 12). Based on standard curve calibration, several thousand viruses per minute were observed in the tested exhalations. Furthermore, referring to the average tidal volume data of adults, it was estimated that an exhaled SARS-CoV-2 concentration of approximately one copy/mL is detectable for COVID-19 patients. This study validates the original concept of breath detection of SARS-CoV-2 using SAC combined with RT-PCR.
Strain, Soil-Type, Irrigation Regimen, and Poultry Litter Influence Salmonella Survival and Die-off in Agricultural Soils
Authors: Bardsley Cameron A. , Weller Daniel L. , Ingram David T. , Chen Yuhuan , Oryang David , Rideout Steven L. , Strawn Laura K.
Published: March 2021

The use of untreated biological soil amendments of animal origin (BSAAO) have been identified as one potential mechanism for the dissemination and persistence of Salmonella in the produce growing environment. Data on factors influencing Salmonella concentration in amended soils are therefore needed. The objectives here were to (i) compare die-off between 12 Salmonella strains following inoculation in amended soil and (ii) characterize any significant effects associated with soil-type, irrigation regimen, and amendment on Salmonella survival and die-off. Three greenhouse trials were performed using a randomized complete block design. Each strain (~4 log CFU/g) was homogenized with amended or non-amended sandy-loam or clay-loam soil. Salmonella levels were enumerated in 25 g samples 0, 0.167 (4 h), 1, 2, 4, 7, 10, 14, 21, 28, 56, 84, 112, 168, 210, 252, and 336 days post-inoculation (dpi), or until two consecutive samples were enrichment negative. Regression analysis was performed between strain, soil-type, irrigation, and (i) time to last detect (survival) and (ii) concentration at each time-point (die-off rate). Similar effects of strain, irrigation, soil-type, and amendment were identified using the survival and die-off models. Strain explained up to 18% of the variance in survival, and up to 19% of variance in die-off rate. On average Salmonella survived for 129 days in amended soils, however, Salmonella survived, on average, 30 days longer in clay-loam soils than sandy-loam soils [95% Confidence interval (CI) = 45, 15], with survival time ranging from 84 to 210 days for the individual strains during daily irrigation. When strain-specific associations were investigated using regression trees, S. Javiana and S. Saintpaul were found to survive longer in sandy-loam soil, whereas most of the other strains survived longer in clay-loam soil. Salmonella also survived, on average, 128 days longer when irrigated weekly, compared to daily (CI = 101, 154), and 89 days longer in amended soils, than non-amended soils (CI = 61, 116). Overall, this study provides insight into Salmonella survival following contamination of field soils by BSAAO. Specifically, Salmonella survival may be strain-specific as affected by both soil characteristics and management practices. These data can assist in risk assessment and strain selection for use in challenge and validation studies.
Enrichment of Food With Tannin Extracts Promotes Healthy Changes in the Human Gut Microbiota
Authors: Molino Silvia , Lerma-Aguilera Alberto , Jiménez-Hernández Nuria , Gosalbes María José , Rufián-Henares José Ángel , Francino M. Pilar
Published: March 2021

Food and food bioactive components are major drivers of modulation of the human gut microbiota. Tannin extracts consist of a mix of bioactive compounds, which are already exploited in the food industry for their chemical and sensorial properties. The aim of our study was to explore the viability of associations between tannin wood extracts of different origin and food as gut microbiota modulators. 16S rRNA amplicon next-generation sequencing (NGS) was used to test the effects on the gut microbiota of tannin extracts from quebracho, chestnut, and tara associated with commercial food products with different composition in macronutrients. The different tannin-enriched and non-enriched foods were submitted to in vitro digestion and fermentation by the gut microbiota of healthy subjects. The profile of the short chain fatty acids (SCFAs) produced by the microbiota was also investigated. The presence of tannin extracts in food promoted an increase of the relative abundance of the genus Akkermansia, recognized as a marker of a healthy gut, and of various members of the Lachnospiraceae and Ruminococcaceae families, involved in SCFA production. The enrichment of foods with tannin extracts had a booster effect on the production of SCFAs, without altering the profile given by the foods alone. These preliminary results suggest a positive modulation of the gut microbiota with potential benefits for human health through the enrichment of foods with tannin extracts.
The Emerging Trend of Bio-Engineering Approaches for Microbial Nanomaterial Synthesis and Its Applications
Authors: Dhanker Raunak , Hussain Touseef , Tyagi Priyanka , Singh Kawal Jeet , Kamble Shashank S.
Published: March 2021

Micro-organisms colonized the world before the multi-cellular organisms evolved. With the advent of microscopy, their existence became evident to the mankind and also the vast processes they regulate, that are in direct interest of the human beings. One such process that intrigued the researchers is the ability to grow in presence of toxic metals. The process seemed to be simple with the metal ions being sequestrated into the inclusion bodies or cell surfaces enabling the conversion into nontoxic nanostructures. However, the discovery of genome sequencing techniques highlighted the genetic makeup of these microbes as a quintessential aspect of these phenomena. The findings of metal resistance genes (MRG) in these microbes showed a rather complex regulation of these processes. Since most of these MRGs are plasmid encoded they can be transferred horizontally. With the discovery of nanoparticles and their many applications from polymer chemistry to drug delivery, the demand for innovative techniques of nanoparticle synthesis increased dramatically. It is now established that microbial synthesis of nanoparticles provides numerous advantages over the existing chemical methods. However, it is the explicit use of biotechnology, molecular biology, metabolic engineering, synthetic biology, and genetic engineering tools that revolutionized the world of microbial nanotechnology. Detailed study of the micro and even nanolevel assembly of microbial life also intrigued biologists and engineers to generate molecular motors that mimic bacterial flagellar motor. In this review, we highlight the importance and tremendous hidden potential of bio-engineering tools in exploiting the area of microbial nanoparticle synthesis. We also highlight the application oriented specific modulations that can be done in the stages involved in the synthesis of these nanoparticles. Finally, the role of these nanoparticles in the natural ecosystem is also addressed.
Microbiome and Metabolome Analyses Reveal Novel Interplay Between the Skin Microbiota and Plasma Metabolites in Psoriasis
Authors: Chen Dongmei , He Jingquan , Li Jinping , Zou Qian , Si Jiawei , Guo Yatao , Yu Jiayu , Li Cheng , Wang Fang , Chan Tianlong , Shi Huijuan
Published: March 2021

Psoriasis is a chronic inflammatory skin disease that affects millions of people worldwide. There is still no effective approach for the clinical treatment of psoriasis. This is largely due to the lack of understanding of the pathological mechanism. Here, we comprehensively characterized the skin microbiome and plasma metabolome alterations of psoriasis patients. We observed that some pathogenic bacteria, includingVibrio, were significantly increased in psoriasis patients. The metabolomics results showed alterations in some metabolic pathways, especially pathways for lipid metabolism. In addition, microbiome-specific metabolites, including bile acids and kynurenine, were significantly changed. Correlation analysis revealed the interplay between the skin microbiota and plasma metabolites, especially betweenVibrioand several lipids. Our results provide new evidence for the interplay between the skin microbiome and plasma metabolites, which is dramatically disrupted in psoriasis patients. This study also revealed the mechanism underlying the pathogenesis of psoriasis.
Higher Abundance of Sediment Methanogens and Methanotrophs Do Not Predict the Atmospheric Methane and Carbon Dioxide Flows in Eutrophic Tropical Freshwater Reservoirs
Authors: Pierangeli Gabrielle Maria Fonseca , Domingues Mercia Regina , Jesus Tatiane Araujo de , Coelho Lúcia Helena Gomes , Hanisch Werner Siegfried , Pompêo Marcelo Luiz Martins , Saia Flávia Talarico , Gregoracci Gustavo Bueno , Benassi Roseli Frederigi
Published: March 2021

Freshwater reservoirs emit greenhouse gases (GHGs) such as methane (CH4) and carbon dioxide (CO2), contributing to global warming, mainly when impacted by untreated sewage and other anthropogenic sources. These gases can be produced by microbial organic carbon decomposition, but little is known about the microbiota and its participation in GHG production and consumption in these environments. In this paper we analyzed the sediment microbiota of three eutrophic tropical urban freshwater reservoirs, in different seasons and evaluated the correlations between microorganisms and the atmospheric CH4 and CO2 flows, also correlating them to limnological variables. Our results showed that deeper water columns promote high methanogen abundance, with predominance of acetoclastic Methanosaeta spp. and hydrogenotrophs Methanoregula spp. and Methanolinea spp. The aerobic methanotrophic community was affected by dissolved total carbon (DTC) and was dominated by Crenothrix spp. However, both relative abundance of the total methanogenic and aerobic methanotrophic communities in sediments were uncoupled to CH4 and CO2 flows. Network based approach showed that fermentative microbiota, including Leptolinea spp. and Longilinea spp., which produces substrates for methanogenesis, influence CH4 flows and was favored by anthropogenic pollution, such as untreated sewage loads. Additionally, less polluted conditions favored probable anaerobic methanotrophs such as Candidatus Bathyarchaeota, Sva0485, NC10, and MBG-D/DHVEG-1, which promoted lower gaseous flows, confirming the importance of sanitation improvement to reduce these flows in tropical urban freshwater reservoirs and their local and global warming impact.
Coculture, An Efficient Biotechnology for Mining the Biosynthesis Potential of Macrofungi via Interspecies Interactions
Authors: Yu Guihong , Sun Yuman , Han Heyang , Yan Xiu , Wang Yu , Ge Xiaoxuan , Qiao Bin , Tan Lingling
Published: March 2021

Macrofungi, which are also known as mushrooms, can produce various bioactive constituents and have become promising resources as lead drugs and foods rich in nutritional value. However, the production of these bioactive constituents under standard laboratory conditions is inefficiency due to the silent expression of their relevant genes. Coculture, as an important activation strategy that simulates the natural living conditions of macrofungi, can activate silent genes or clusters through interspecific interactions. Coculturing not only can trigger the biosynthesis of diverse secondary metabolites and enzymes of macrofungi, but is also useful for uncovering the mechanisms of fungal interspecific interactions and novel gene functions. In this paper, coculturing among macrofungi or between macrofungi and other microorganisms, the triggering and upregulation of secondary metabolites and enzymes, the potential medicinal applications, and the fungal–fungal interaction mechanisms are reviewed. Finally, future challenges and perspectives in further advancing coculture systems are discussed.
White Matter Connectivity and Gray Matter Volume Changes Following Donepezil Treatment in Patients With Mild Cognitive Impairment: A Preliminary Study Using Probabilistic Tractography
Authors: Kim Gwang-Won , Park Shin-Eui , Park Kwangsung , Jeong Gwang-Woo
Published: March 2021

The donepezil treatment is associated with improved cognitive performance in patients with mild cognitive impairment (MCI), and its clinical effectiveness is well-known. However, the impact of the donepezil treatment on the enhanced white matter connectivity in MCI is still unclear. The purpose of this study was to evaluate the thalamo-cortical white matter (WM) connectivity and cortical thickness and gray matter (GM) volume changes in the cortical regions following donepezil treatment in patients with MCI using probabilistic tractography and voxel-based morphometry. Patients with MCI underwent magnetic resonance examinations before and after 6-month donepezil treatment. Compared with healthy controls, patients with MCI showed decreased WM connectivity of the thalamo-lateral prefrontal cortex, as well as reduced thickness in the medial/lateral orbitofrontal cortices (p < 0.05). The thalamo-lateral temporal cortex connectivity in patients with MCI was negatively correlated with Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) (r = −0.76, p = 0.01). The average score of the Korean version of the mini-mental state examination (K-MMSE) in patients with MCI was improved by 7.9% after 6-months of donepezil treatment. However, the patterns of WM connectivity and brain volume change in untreated and treated patients were not significantly different from each other, resulting from multiple comparison corrections. These findings will be valuable in understanding the neurophysiopathological mechanism on MCI as a prodromal phase of Alzheimer's disease in connection with brain functional connectivity and morphometric change.
A Relational Adaptive Neural Model for Joint Entity and Relation Extraction
Authors: Duan Guiduo , Miao Jiayu , Huang Tianxi , Luo Wenlong , Hu Dekun
Published: March 2021

Relation extraction is a popular subtask in natural language processing (NLP). In the task of entity relation joint extraction, overlapping entities and multi-type relation extraction in overlapping triplets remain a challenging problem. The classification of relations by sharing the same probability space will ignore the correlation information among multiple relations. A relational-adaptive entity relation joint extraction model based on multi-head self-attention and densely connected graph convolution network (which is called MA-DCGCN) is proposed in the paper. In the model, the multi-head attention mechanism is specifically used to assign weights to multiple relation types among entities so as to ensure that the probability space of multiple relation is not mutually exclusive. This mechanism also predicts the strength of the relationship between various relationship types and entity pairs flexibly. The structure information of deeper level in the text graph is extracted by the densely connected graph convolution network, and the interaction information of entity relation is captured. To demonstrate the superior performance of our model, we conducted a variety of experiments on two widely used public datasets, NYT and WebNLG. Extensive results show that our model achieves state-of-the-art performance. Especially, the detection effect of overlapping triplets is significantly improved compared with the several existing mainstream methods.
Endocannabinoids and Dopamine Balance Basal Ganglia Output
Authors: Gorodetski Lilach , Loewenstern Yocheved , Faynveitz Anna , Bar-Gad Izhar , Blackwell Kim T. , Korngreen Alon
Published: March 2021

The entopeduncular nucleus is one of the basal ganglia's output nuclei, thereby controlling basal ganglia information processing. Entopeduncular nucleus neurons integrate GABAergic inputs from the Striatum and the globus pallidus, together with glutamatergic inputs from the subthalamic nucleus. We show that endocannabinoids and dopamine interact to modulate the long-term plasticity of all these primary afferents to the entopeduncular nucleus. Our results suggest that the interplay between dopamine and endocannabinoids determines the balance between direct pathway (striatum) and indirect pathway (globus pallidus) in entopeduncular nucleus output. Furthermore, we demonstrate that, despite the lack of axon collaterals, information is transferred between neighboring neurons in the entopeduncular nucleus via endocannabinoid diffusion. These results transform the prevailing view of the entopeduncular nucleus as a feedforward “relay” nucleus to an intricate control unit, which may play a vital role in the process of action selection.
MPV17 Mutations Are Associated With a Quiescent Energetic Metabolic Profile
Authors: Jacinto Sandra , Guerreiro Patrícia , de Oliveira Rita Machado , Cunha-Oliveira Teresa , Santos Maria João , Grazina Manuela , Rego Ana Cristina , Outeiro Tiago F.
Published: March 2021

Mutations in the MPV17 gene are associated with hepatocerebral form of mitochondrial depletion syndrome. The mechanisms through which MPV17 mutations cause respiratory chain dysfunction and mtDNA depletion is still unclear. The MPV17 gene encodes an inner membrane mitochondrial protein that was recently described to function as a non-selective channel. Although its exact function is unknown, it is thought to be important in the maintenance of mitochondrial membrane potential (ΔΨm). To obtain more information about the role of MPV17 in human disease, we investigated the effect of MPV17 knockdown and of selected known MPV17 mutations associated with MPV17 disease in vitro. We used different approaches in order to evaluate the cellular consequences of MPV17 deficiency. We found that lower levels of MPV17 were associated with impaired mitochondrial respiration and with a quiescent energetic metabolic profile. All the mutations studied destabilized the protein, resulting in reduced protein levels. We also demonstrated that different mutations caused different cellular abnormalities, including increased ROS production, decreased oxygen consumption, loss of ΔΨm, and mislocalization of MPV17 protein. Our study provides novel insight into the molecular effects of MPV17 mutations and opens novel possibilities for testing therapeutic strategies for a devastating group of disorders.
Effects of CRMP2 DNA Methylation in the Hippocampus on Depressive-Like Behaviors and Cytoskeletal Proteins in Rats
Authors: Xiang Dan , Sun Siqi , Wang Gaohua , Liu Zhongchun
Published: March 2021

Chronic stress appears to alter DNA methylation and DNA methyltransferases (DNMTs) in brain regions related to emotion. Collapsin response mediator protein-2 (CRMP2) mediates the development of depression by regulating microtubule dynamics. In this study, rats were subjected to chronic unpredictable mild stress (CUMS). At the end of the CUMS procedure, normal saline or fluoxetine was administered to the rats. Moreover, normal saline or the 5-aza-2’-deoxycytidine (5-aza) was administered to the hippocampal CA1 region of the rats. Behavioral tests were performed to evaluate the depressive-like phenotypes. The CRMP2 DNA methylation levels and cytoskeletal microtubular system-related biomarkers were detected by several molecular biology techniques. The results showed that the rat model of depression was successfully established by exposure to CUMS, and fluoxetine treatment exerted an antidepressant-like effect. We observed the upregulation of DNMT1 and DNMT3a in the hippocampus of stressed rats. CUMS induced a decrease in CRMP2 expression and an increase in phosphorylated CRMP2 (pCRMP2) expression in the hippocampus of rats. The rate of DNA methylation in the CpG island of the CRMP2 promoter region in the hippocampus of stressed rats was significantly higher than that in control rats. Moreover, CUMS significantly decreased the interaction between CRMP2 and α-tubulin and decreased the microtubule dynamics. Chronic fluoxetine treatment reversed these changes. Also, hypomethylation induced by 5-aza injection into the hippocampal CA1 region caused antidepressant-like effects and increased CRMP2 expression and microtubule dynamics. These results suggested that CRMP2 DNA methylation may be involved in regulating the cytoskeletal microtubular system and mediating depressive-like behaviors.
Exergaming as Part of the Telerehabilitation Can Be Adequate to the Outpatient Training: Preliminary Findings of a Non-randomized Pilot Study in Parkinson's Disease
Authors: Cikajlo Imre , Hukić Alma , Zajc Dejana
Published: March 2021

Parkinson's disease is a long-term and progressive degenerative disorder of the nervous system, affecting primarily motor coordination, noticeable as a tremor in one hand. Recent studies reported on positive outcomes of intensive physiotherapy of upper extremities. We built a telerehabilitation system with virtual pick and place tasks for small scale hand movements, and designed a pilot study to find whether such exergaming as a telerehabilitation service provides comparable outcomes as an outpatient exergaming service. A non-randomized pilot trial was designed. Hospital outpatients (28/40) with Parkinson's disease were recruited. Those meeting the inclusion criteria were divided into two groups; seven outpatients were assigned to the home (H) group and 21 outpatients to the hospital (URI) group. Both groups received 10 days of exergaming over the course of 2 weeks, each daily session lasting a maximum of 1 h. Primary outcomes were clinical tests; Box and Blocks Test (BBT), Jebsen Hand Function Test (JHFT), and Unified Parkinson's Disease Rating Scale (UPDRS part III) were carried out before and after the study. Secondary outcomes were hand kinematics and exergaming results; number of successfully moved objects and task time. Statistical analysis was carried out to find significant (p < 0.05) differences and Cohen's U3 was used to determine effect sizes. The differences between the groups in gender (p = 0.781), age (p = 0.192), and duration of the disease (p = 0.195) were tested with Bartlett's test and no statistical differences were found with an F test. Both groups demonstrated statistically significant improvements in clinical test UDPRS III (p = 0.006 and p = 0.011) and the hospital group also in BBT (p = 0.002) and JHFT (p = 0.015) and with UDPRS III and JHFT even in favor of the home group (χ2 = 5.08, p = 0.024, χ2 = 7.76, p = 0.005). Nevertheless, the exergaming results show significant improvement after training (U3 > 0.86). Exergaming has already been suggested as an effective approach in the planning of rehabilitation tasks for persons with Parkinson's disease. We have prepared a pilot study demonstrating that exergaming at home with telerehabilitation support may provide comparable clinical outcomes. The study shall be followed by a randomized study with higher statistical power to provide clinical evidence. Nevertheless, carrying out even part of the rehabilitation program at home is crucial for the development of future telerehabilition clinical services.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03175107.