bluuebunny/crossref_metadata_2025 huggingface dataset:
Cenozoic Uplift of Tanggula Range and Tuouohe Basin, Northern Tibet: Insights of the Anisotropy of Magnetic Susceptibility
Authors: Li Leyi , Chang Hong , Pares Josep M. , Bradák Balázs , Zhang Zeke , Qiang Xiaoke , Guan Chong , Quan Chunyan
Published: April 2022

The timing and intensity of deformation of the Tanggula Range and Tuotuohe Basin are in debatable but strengthening the research on them is necessary for better understanding the geodynamic models of the Tibet and the tectonic-climate connections during the Cenozoic. Here we present the anisotropy of magnetic susceptibility (AMS) records from the foreland Tuotuohe Basin to understand the tectonic uplift history of the Tanggula Range for the interval of ∼37–19.7 Ma. Rock magnetic analyses indicate that the main magnetic carrier is paramagnetic and the minor is hematite. Thus, the AMS in the Tuotuohe Section (TS) can be used to track the tectonic strain related to tectonic processes. The distribution direction of the maximum principle susceptibility (Kmax) is approximately NW–SE, which intersects at about 10°with the strike of the strata and is nearly parallel to the Tanggula thrust fault system, whereas the minimum principle susceptibility (Kmin) is oriented in the NE–SW direction with a girdle distribution. This is consistent with the sedimentary fabric imprinted by the NE–SW shortening direction, representing the earliest deformation stage. AMS data in the TS can be divided into two phases at 30 Ma. From ∼37 to 30 Ma, the AMS parameters indicate an active tectonic strain and the Tanggula Range uplift induced by the India–Asia convergence, whereas between 30 and 19.7 Ma, the strain is weak compared with the earlier phase. Finally, the weak strain environment between 30 and 19.7 Ma indicated by the AMS indexes of the TS and the paleoelevation evidence from the Tuotuohe Basin all together suggest that an additional 1000–2000 m of surface uplift of the basin may have begun after 19.7 Ma.
Late Permian to Late Triassic Large Igneous Provinces: Timing, Eruptive Style and Paleoenvironmental Perturbations
Authors: Boscaini Andrea , Callegaro Sara , Sun Yadong , Marzoli Andrea
Published: April 2022

The emplacement of the Siberian Traps, the Central Atlantic Magmatic Province (CAMP) and the Wrangellia have been linked to the end-Permian, the end-Triassic mass extinctions, and to the Carnian Pluvial Episode (CPE), respectively. Exploring the timing, eruptive styles, and volatile degassing of these Large Igneous Provinces (LIPs) is crucial to understand their causal link to the catastrophic environmental crises that punctuated the Triassic. In this study we review the main characteristics of these LIPs, emphasizing common features and differences, and discussing aspects that are still in debate. Estimates of CO2 budgets and emissions from the three LIPs are based on the Nb content of little evolved basalts and highlight that early Siberian Traps and CAMP and high-Ti Wrangellia volcanics were quite CO2-rich. On the contrary, other volcanics from the three LIPs probably emitted relatively low amounts of CO2, which reinforces the possibility that thermogenic reactions between sills and sediments were additional fundamental suppliers of climate-modifying gases.
Process and Controlling Factors of Pore Evolution in Marine-Continental Transitional Black Shale—An Example From Permian Shanxi Formation in the Eastern Margin of Ordos Basin
Authors: Wu Jin , Zhang Xiaowei , Xu Hao , Xiao Yufeng , Liu Guiying , Jiang Lingfeng , Deng Naier , Ren Zihe
Published: April 2022

Pore and pore network evolution of shale is critical for the evaluation the pore system in shale gas reservoirs. Thermal maturation effect acts as an indispensable role in porosity evolution. In this paper, high-temperature and high-pressure in-situ thermal simulation experiments were conducted to investigate the process and controlling factors of pore evolution in marine-continental transitional shale. Multiple methods, including scanning electron microscopy (SEM), X-ray diffraction, helium porosimetry and low-pressure N2 and CO2 adsorption were used to investigate the evolution of mineral composition and pore structure at different stages of thermal maturity. The results showed that type III organic matter (OM) generated petroleum with the thermal maturity increasing. The total organic carbon (TOC) decreased by 13.3% when temperature reached 607°C. At the same time, it produced numerous organic and mineral pores during hydrocarbon generation. Besides, some changes in mineral composition have occurred, especially in illite (from 11% to 31%) and kaolinite (from 89% to 69%). In general, it can divide into 3 stages (maturity, high maturity and over maturity) for shale pore system evolution with the thermal maturity increasing. In the low maturity period, large amounts of pyrolytic bitumen and oil generated to fill the pores, causing the pore system to diminish; in the high maturity period, a large number of pores were generated when oil is cracked into gas, resulting in a rapid expansion of the pore system; in the over-maturity period, the cracking of pyrolysis and hydrocarbon slowed down, allowing the pore system to stabilize. Shale pore evolution is primarily controlled by the thermal evolution of OM, and the conversion of inorganic minerals contributes less to pore evolution compared to organic matter. The high maturity period (1.2% < Ro < 2.0%) was the period when extensive pyrolysis and hydrocarbon generated in the Shanxi Formation shale, which contributed mostly for the pores generation and accumulation of shale gas.
Research on Damping Contribution Rate of Key Parameters of Valve-Controlled Damping Adjustable Damper
Authors: Xie Fangwei , Shi Xiuwei , Cao Jinxin , Ding Zhiwen , Yu Chengcheng , Gao Yonghua
Published: April 2022

Valve-controlled damping adjustable damper has the characteristics of simple structure and adjustable damping, and it has always been a hot research topic. This paper establishes a mathematical model of damping characteristics of the valve-controlled damping adjustable damper and designs the experiment of the damping characteristics of the compression stroke and the recovery stroke. Through simulation and experiment, the accuracy of the mathematical model is verified, and the damping contribution rate of different key parameters under different excitation speeds is analyzed. The results show that the mathematical model of the damping characteristics can well describe the working state of the damper. The damping contribution rate of key parameters under different excitation speeds is obtained. The damping contribution of the constant through-hole diameter decreases gradually after the valve is opened for the first time. With the increase of the excitation speed, the valve plate equivalent thickness and the valve plate maximum limit clearance of the check valve gradually play a major role in the damping contribution rate. The research results can screen out the key parameters, improve the development efficiency of the damper, and provide guidance for the damper design and optimization.
Improper Maintenance Activities Alter Benefits of Urban Stormwater Treatment in a Temperate Constructed Wetland in NSW, Australia
Authors: Wright Aaron S. , Doblin Martina A. , Scanes Peter R.
Published: April 2022

Constructed wetlands (CWs) are an effective means to treat nutrient and sediment pollution in urban stormwater runoff to minimise impact on receiving waterways. Maintenance of devices is recognised as a major contributing factor to performance. There is a lack of evidence-based guidance on maintenance activities to optimise treatment, due to a paucity of data from long-term field studies into CW performance before and after maintenance. In this study, the nutrient and sediment removal efficiency (% RE) of a CW was evaluated by calculating removal efficiencies of nitrogen (N), phosphorus (P) and total suspended sediment (TSS) following a long-term sampling program under baseflow and event flow conditions. Sampling was carried out before, during and after maintenance. Maintenance involved removing all aquatic vegetation and 200–300 mm of sediments over a 3-week period, aiming to improve the wetland’s performance. Assessment of dissolved and particulate nutrient fractions allowed a comprehensive investigation into drivers of nutrient removal efficiency. Under baseflow conditions differences in inflow and outflow pollutant concentrations were used to calculate removal efficiency and pollutant loads were used during event flow conditions. Before maintenance, during baseflow conditions the wetland was removing total N (36% RE) but exporting total P (-52% RE) and total sediment (-94% RE). During event-flow conditions all target pollutants were being removed (total N 63% RE, total P 25% RE and TSS 69% RE). phosphorusDuring maintenance, the device continued to remove total N (18% RE) but the physical disturbance of the maintenance resulted in mass export of total P (-120% RE) and total sediment (−2,000% RE) over a short time period, effectively undoing previous treatment. After maintenance, during baseflow conditions, the wetlands’ ability to treat total N decreased (28% RE), improved for total P (1% RE), and became a chronic source of suspended sediment (−127% RE). During event flow conditions, total N was no longer being treated (−19%) but total P and total suspended sediment were being retained (74%, 80% RE respectively). This study showed that the physical disturbance resulting from large-scale maintenance activities can potentially reverse years’ worth of treatment if not adequately planned and carried out with suitable controls.
miRModuleNet: Detecting miRNA-mRNA Regulatory Modules
Authors: Yousef Malik , Goy Gokhan , Bakir-Gungor Burcu
Published: April 2022

Increasing evidence that microRNAs (miRNAs) play a key role in carcinogenesis has revealed the need for elucidating the mechanisms of miRNA regulation and the roles of miRNAs in gene-regulatory networks. A better understanding of the interactions between miRNAs and their mRNA targets will provide a better understanding of the complex biological processes that occur during carcinogenesis. Increased efforts to reveal these interactions have led to the development of a variety of tools to detect and understand these interactions. We have recently described a machine learning approach miRcorrNet, based on grouping and scoring (ranking) groups of genes, where each group is associated with a miRNA and the group members are genes with expression patterns that are correlated with this specific miRNA. The miRcorrNet tool requires two types of -omics data, miRNA and mRNA expression profiles, as an input file. In this study we describe miRModuleNet, which groups mRNA (genes) that are correlated with each miRNA to form a star shape, which we identify as a miRNA-mRNA regulatory module. A scoring procedure is then applied to each module to further assess their contribution in terms of classification. An important output of miRModuleNet is that it provides a hierarchical list of significant miRNA-mRNA regulatory modules. miRModuleNet was further validated on external datasets for their disease associations, and functional enrichment analysis was also performed. The application of miRModuleNet aids the identification of functional relationships between significant biomarkers and reveals essential pathways involved in cancer pathogenesis. The miRModuleNet tool and all other supplementary files are available at https://github.com/malikyousef/miRModuleNet/
A Rare Presentation Characterized by Epileptic Spasms in ALDH7A1, Pyridox(am)ine-5′-Phosphate Oxidase, and PLPBP Deficiency
Authors: Jiao Xianru , Gong Pan , Niu Yue , Zhang Yuehua , Yang Zhixian
Published: April 2022

Objective: To analyze the clinical feature, treatment, and prognosis of epileptic spasms (ES) in vitamin B6–dependent epilepsy, including patients with pyridoxine-dependent epilepsy (PDE) caused by ALDH7A1 mutation, pyridox(am)ine-5′-phosphate oxidase (PNPO) deficiency, and PLPBP deficiency.

Methods: We analyzed data from a cohort of 54 cases with PDE, 13 cases with PNPO deficiency, and 2 cases with PLPBP deficiency and looked for the presentation of ES among them.

Results: A total of 11 patients with the seizure presentation of ES have been collected. Among them, four patients carried mutations in ALDH7A1, six carried mutations in PNPO, and the remaining one carried mutation in PLPBP. The analysis of this cohort identified nine cases presenting as infantile spasms distributed in the three diseases and two cases presenting as Ohtahara syndrome diagnosed with PDE and PNPO deficiency, respectively. In the PDE and PLPBP deficiency groups, seizures were controlled by pyridoxine monotherapy, and the remaining one had refractory seizures due to secondary brain atrophy. In the groups with PNPO deficiency, one patient showed seizure-free when treated by PLP combined with valproic acid, three still had infrequent seizures treated by PLP monotherapy or pyridoxine or PLP combined with other antiseizure medications, and two died. In two cases presenting as Ohtahara syndrome, after regular treatment, one showed seizure-free, the others showed a marked decrease in seizure frequency, and they both showed an improvement in EEG.

Significance: ES might be a common form of seizures in PNPO deficiency, and EEG presented as hypsarrhythmia or a burst suppression pattern. It is difficult for pyridoxine to control frequent seizures caused by secondary brain injury. In our PNPO deficiency cohort, patients with infantile spasms did not respond better to PLP than pyridoxine. Timely and correct treatment could prevent the transformation of the child’s disease from Ohtahara syndrome and infantile spasms to subsequent epileptic encephalopathy or refractory epilepsy.
PAGER Web APP: An Interactive, Online Gene Set and Network Interpretation Tool for Functional Genomics
Authors: Yue Zongliang , Slominski Radomir , Bharti Samuel , Chen Jake Y.
Published: April 2022

Functional genomics studies have helped researchers annotate differentially expressed gene lists, extract gene expression signatures, and identify biological pathways from omics profiling experiments conducted on biological samples. The current geneset, network, and pathway analysis (GNPA) web servers, e.g., DAVID, EnrichR, WebGestaltR, or PAGER, do not allow automated integrative functional genomic downstream analysis. In this study, we developed a new web-based interactive application, “PAGER Web APP”, which supports online R scripting of integrative GNPA. In a case study of melanoma drug resistance, we showed that the new PAGER Web APP enabled us to discover highly relevant pathways and network modules, leading to novel biological insights. We also compared PAGER Web APP’s pathway analysis results retrieved among PAGER, EnrichR, and WebGestaltR to show its advantages in integrative GNPA. The interactive online web APP is publicly accessible from the link, https://aimed-lab.shinyapps.io/PAGERwebapp/.
Fluvalinate-Induced Changes in MicroRNA Expression Profile of Apis mellifera ligustica Brain Tissue
Authors: Tianle Chao , Liuxu Yang , Delong Lou , Yunhan Fan , Yu He , Xueqing Shan , Haitao Xia , Guizhi Wang
Published: April 2022

Fluvalinate is a widely used and relatively safe acaricide for honeybees, but it still has a negative impact on honeybee colonies. Such negative effects may be related to fluvalinate-induced brain nerve tissue damage, but the detailed molecular regulatory mechanism of this phenomenon is still poorly understood. In this study, we analyzed the miRNA expression profile changes in the brain tissue of Apis mellifera ligustica by miRNA sequencing after fluvalinate treatment. A total of 1,350 miRNAs were expressed in Apis mellifera ligustica brain tissue, of which only 180 were previously known miRNAs in honeybees. Among all known and novel miRNAs, 15 were differentially expressed between at least two of the four time periods before and after fluvalinate administration. Further analysis revealed five significantly enriched KEGG pathways of the differentially expressed miRNA (DEM) potential target genes, namely, “Hippo signaling pathway-fly,” “Phototransduction-fly,” “Apoptosis-fly,” “Wnt signaling pathway,” and “Dorso-ventral axis formation,” which indicates that differentially expressed miRNA function may be related to cell apoptosis and memory impairment in the fluvalinate-treated Apis mellifera ligustica brain. Ame-miR-3477-5p, ame-miR-375-3p, and miR-281-x were identified as key miRNAs. Overall, our research provides new insights into the roles of miRNAs in brain tissue during the process of fluvalinate-induced Apis mellifera ligustica poisoning.
Unraveling the Genetic Architecture of Hepatoblastoma Risk: Birth Defects and Increased Burden of Germline Damaging Variants in Gastrointestinal/Renal Cancer Predisposition and DNA Repair Genes
Authors: Aguiar Talita , Teixeira Anne , Scliar Marília O. , Sobral de Barros Juliana , Lemes Renan B. , Souza Silvia , Tolezano Giovanna , Santos Fernanda , Tojal Israel , Cypriano Monica , Caminada de Toledo Silvia Regina , Valadares Eugênia , Borges Pinto Raquel , Pinto Artigalas Osvaldo Afonso , Caetano de Aguirre Neto Joaquim , Novak Estela , Cristofani Lilian Maria , Miura Sugayama Sofia M. , Odone Vicente , Cunha Isabela Werneck , Lima da Costa Cecilia Maria , Rosenberg Carla , Krepischi Ana
Published: April 2022

The ultrarare hepatoblastoma (HB) is the most common pediatric liver cancer. HB risk is related to a few rare syndromes, and the molecular bases remain elusive for most cases. We investigated the burden of rare damaging germline variants in 30 Brazilian patients with HB and the presence of additional clinical signs. A high frequency of prematurity (20%) and birth defects (37%), especially craniofacial (17%, including craniosynostosis) and kidney (7%) anomalies, was observed. Putative pathogenic or likely pathogenic monoallelic germline variants mapped to 10 cancer predisposition genes (CPGs: APC, CHEK2, DROSHA, ERCC5, FAH, MSH2, MUTYH, RPS19, TGFBR2 and VHL) were detected in 33% of the patients, only 40% of them with a family history of cancer. These findings showed a predominance of CPGs with a known link to gastrointestinal/colorectal and renal cancer risk. A remarkable feature was an enrichment of rare damaging variants affecting different classes of DNA repair genes, particularly those known as Fanconi anemia genes. Moreover, several potentially deleterious variants mapped to genes impacting liver functions were disclosed. To our knowledge, this is the largest assessment of rare germline variants in HB patients to date, contributing to elucidate the genetic architecture of HB risk.
Persistence of SARS-CoV-2 Antibodies in Vaccinated Health Care Workers Analyzed by Coronavirus Antigen Microarray
Authors: Hosseinian Sina , Powers Kathleen , Vasudev Milind , Palma Anton M. , de Assis Rafael , Jain Aarti , Horvath Peter , Birring Paramveer S. , Andary Rana , Au Connie , Chin Brandon , Khalil Ghali , Ventura Jenny , Luu Madeleine K. , Figueroa Cesar , Obiero Joshua M. , Silzel Emily , Nakajima Rie , Gombrich William Thomas , Jasinskas Algis , Zaldivar Frank , Schubl Sebastian , Felgner Philip L. , Khan Saahir ,   The Specimen Collection Group
Published: April 2022

Recent studies provide conflicting evidence on the persistence of SARS-CoV-2 immunity induced by mRNA vaccines. Here, we aim to quantify the persistence of humoral immunity following vaccination using a coronavirus antigen microarray that includes 10 SARS-CoV-2 antigens. In a prospective longitudinal cohort of 240 healthcare workers, composite SARS-CoV-2 IgG antibody levels did not wane significantly over a 6-month study period. In the subset of the study population previously exposed to SARS-CoV-2 based on seropositivity for nucleocapsid antibodies, higher composite anti-spike IgG levels were measured before the vaccine but no significant difference from unexposed individuals was observed at 6 months. Age, vaccine type, or worker role did not significantly impact composite IgG levels, although non-significant trends towards lower antibody levels in older participants and higher antibody levels with Moderna vaccine were observed at 6 months. A small subset of our cohort were classified as having waning antibody titers at 6 months, and these individuals were less likely to work in patient care roles and more likely to have prior exposure to SARS-CoV-2.
Staphylococcus aureus Multiplexes Death-Effector Deoxyribonucleosides to Neutralize Phagocytes
Authors: Tantawy Eshraq , Schwermann Nicoletta , Ostermeier Tjorven , Garbe Annette , Bähre Heike , Vital Marius , Winstel Volker
Published: April 2022

Adenosine synthase A (AdsA) is a key virulence factor of Staphylococcus aureus, a dangerous microbe that causes fatal diseases in humans. Together with staphylococcal nuclease, AdsA generates deoxyadenosine (dAdo) from neutrophil extracellular DNA traps thereby igniting caspase-3-dependent cell death in host immune cells that aim at penetrating infectious foci. Powered by a multi-technological approach, we here illustrate that the enzymatic activity of AdsA in abscess-mimicking microenvironments is not restricted to the biogenesis of dAdo but rather comprises excessive biosynthesis of deoxyguanosine (dGuo), a cytotoxic deoxyribonucleoside generated by S. aureus to eradicate macrophages of human and animal origin. Based on a genome-wide CRISPR-Cas9 knock-out screen, we further demonstrate that dGuo-induced cytotoxicity in phagocytes involves targeting of the mammalian purine salvage pathway-apoptosis axis, a signaling cascade that is concomitantly stimulated by staphylococcal dAdo. Strikingly, synchronous targeting of this route by AdsA-derived dGuo and dAdo boosts macrophage cell death, indicating that S. aureus multiplexes death-effector deoxyribonucleosides to maximize intra-host survival. Overall, these data provide unique insights into the cunning lifestyle of a deadly pathogen and may help to design therapeutic intervention strategies to combat multidrug-resistant staphylococci.
Ex Vivo Test for Measuring Complement Attack on Endothelial Cells: From Research to Bedside
Authors: Meuleman Marie-Sophie , Duval Anna , Fremeaux-Bacchi Véronique , Roumenina Lubka T. , Chauvet Sophie
Published: April 2022

As part of the innate immune system, the complement system plays a key role in defense against pathogens and in host cell homeostasis. This enzymatic cascade is rapidly triggered in the presence of activating surfaces. Physiologically, it is tightly regulated on host cells to avoid uncontrolled activation and self-damage. In cases of abnormal complement dysregulation/overactivation, the endothelium is one of the primary targets. Complement has gained momentum as a research interest in the last decade because its dysregulation has been implicated in the pathophysiology of many human diseases. Thus, it appears to be a promising candidate for therapeutic intervention. However, detecting abnormal complement activation is challenging. In many pathological conditions, complement activation occurs locally in tissues. Standard routine exploration of the plasma concentration of the complement components shows values in the normal range. The available tests to demonstrate such dysregulation with diagnostic, prognostic, and therapeutic implications are limited. There is a real need to develop tools to demonstrate the implications of complement in diseases and to explore the complex interplay between complement activation and regulation on human cells. The analysis of complement deposits on cultured endothelial cells incubated with pathologic human serum holds promise as a reference assay. This ex vivo assay most closely resembles the physiological context. It has been used to explore complement activation from sera of patients with atypical hemolytic uremic syndrome, malignant hypertension, elevated liver enzymes low platelet syndrome, sickle cell disease, pre-eclampsia, and others. In some cases, it is used to adjust the therapeutic regimen with a complement-blocking drug. Nevertheless, an international standard is lacking, and the mechanism by which complement is activated in this assay is not fully understood. Moreover, primary cell culture remains difficult to perform, which probably explains why no standardized or commercialized assay has been proposed. Here, we review the diseases for which endothelial assays have been applied. We also compare this test with others currently available to explore complement overactivation. Finally, we discuss the unanswered questions and challenges to overcome for validating the assays as a tool in routine clinical practice.
Optimizing the Boosting Schedule of Subunit Vaccines Consisting of BCG and “Non-BCG” Antigens to Induce Long-Term Immune Memory
Authors: Lv Wei , He Pu , Ma Yanlin , Tan Daquan , Li Fei , Xie Tao , Han Jiangyuan , Wang Juan , Mi Youjun , Niu Hongxia , Zhu Bingdong
Published: April 2022

Boosting Bacillus Calmette-Guérin (BCG) with subunit vaccine is expected to induce long-term protection against tuberculosis (TB). However, it is urgently needed to optimize the boosting schedule of subunit vaccines, which consists of antigens from or not from BCG, to induce long-term immune memory. To address it two subunit vaccines, Mtb10.4-HspX (MH) consisting of BCG antigens and ESAT6-CFP10 (EC) consisting of antigens from the region of difference (RD) of Mycobacterium tuberculosis (M. tuberculosis), were applied to immunize BCG-primed C57BL/6 mice twice or thrice with different intervals, respectively. The long-term antigen-specific immune responses and protective efficacy against M. tuberculosis H37Ra were determined. The results showed that following BCG priming, MH boosting twice at 12-24 weeks or EC immunizations thrice at 12-16-24 weeks enhanced the number and function of long-lived memory T cells with improved protection against H37Ra, while MH boosting thrice at 12-16-24 weeks or twice at 8-14 weeks and EC immunizations twice at 12-24 weeks or thrice at 8-10-14 weeks didn’t induce long-term immunity. It suggests that following BCG priming, both BCG antigens MH boosting twice and “non-BCG” antigens EC immunizations thrice at suitable intervals induce long-lived memory T cell-mediated immunity.
Automated Disease Detection in Gastroscopy Videos Using Convolutional Neural Networks
Authors: Zhang Chenxi , Xiong Zinan , Chen Shuijiao , Ding Alex , Cao Yu , Liu Benyuan , Liu Xiaowei
Published: April 2022

A large percentage of the world's population is affected by gastric diseases ranging from erosion and ulcer to serious ailments such as gastric cancer, which is mainly caused by Helicobacter pylori(H.pylori) infection. While most erosions and ulcers are benign, severe cases of gastric diseases can still develop into cancer. Thus, early screening and treatment of all gastric diseases are of great importance. Upper gastroscopy is one such common screening procedure that visualizes the patient's upper digestive system by inserting a camera attached to a rubber tube down the patient's digestive tracts, but since the procedure requires manual inspection of the video feed, it is prone to human errors. To improve the sensitivity and specificity of gastroscopies, we applied deep learning methods to develop an automated gastric disease detection system that detects frames of the video feed showing signs of gastric diseases. To this end, we collected data from images in anonymous patient case reports and gastroscopy videos to train and evaluate a convolutional neural network (CNN), and we used sliding window to improve the stability of our model's video performance. Our CNN model achieved 84.92% sensitivity, 88.26% specificity, and 85.2% F1-score on the test set, as well as 97% true positive rate and 16.2% false positive rate on a separate video test set.
Development of an in vitro Model of Human Gut Microbiota for Screening the Reciprocal Interactions With Antibiotics, Drugs, and Xenobiotics
Authors: El Houari Abdelaziz , Ecale Florine , Mercier Anne , Crapart Stéphanie , Laparre Jérôme , Soulard Baptiste , Ramnath Manilduth , Berjeaud Jean-Marc , Rodier Marie-Hélène , Crépin Alexandre
Published: April 2022

Altering the gut microbiota can negatively affect human health. Efforts may be sustained to predict the intended or unintended effects of molecules not naturally produced or expected to be present within the organism on the gut microbiota. Here, culture-dependent and DNA-based approaches were combined to UHPLC-MS/MS analyses in order to investigate the reciprocal interactions between a constructed Human Gut Microbiota Model (HGMM) and molecules including antibiotics, drugs, and xenobiotics. Our HGMM was composed of strains from the five phyla commonly described in human gut microbiota and belonging to Firmicutes, Bacteroidetes, Proteobacteria, Fusobacteria, and Actinobacteria. Relevantly, the bacterial diversity was conserved in our constructed human gut model through subcultures. Uneven richness distribution was revealed and the sensitivity of the HGMM was mainly affected by antibiotic exposure rather than by drugs or xenobiotics. Interestingly, the constructed model and the individual cultured strains respond with the same sensitivity to the different molecules. UHPLC-MS/MS analyses revealed the disappearance of some native molecules in the supernatants of the HGMM as well as in those of the individual strains. These results suggest that biotransformation of molecules occurred in the presence of our gut microbiota model and the coupled approaches performed on the individual cultures may emphasize new bacterial strains active in these metabolic processes. From this study, the new HGMM appears as a simple, fast, stable, and inexpensive model for screening the reciprocal interactions between the intestinal microbiota and molecules of interest.
Differential Modulation of the European Sea Bass Gut Microbiota by Distinct Insect Meals
Authors: Rangel Fábio , Enes Paula , Gasco Laura , Gai Francesco , Hausmann Bela , Berry David , Oliva-Teles Aires , Serra Claudia R. , Pereira Fátima C.
Published: April 2022

The aquaculture industry is one of the fastest-growing sectors in animal food production. However, farming of carnivorous fish strongly relies on the use of wild fish-based meals, a practice that is environmentally and economically unsustainable. Insect-based diets constitute a strong candidate for fishmeal substitution, due to their high nutritional value and low environmental footprint. Nevertheless, data on the impact of insect meal (IM) on the gut microbiome of farmed fish are so far inconclusive, and very scarce in what concerns modulation of microbial-mediated functions. Here we use high-throughput 16S rRNA gene amplicon sequencing and quantitative PCR to evaluate the impact of different IMs on the composition and chitinolytic potential of the European sea bass gut digesta- and mucosa-associated communities. Our results show that insect-based diets of distinct origins differently impact the gut microbiota of the European sea bass (Dicentrarchus labrax). We detected clear modulatory effects of IM on the gut microbiota, which were more pronounced in the digesta, where communities differed considerably among the diets tested. Major community shifts were associated with the use of black soldier fly larvae (Hermetia illucens, HM) and pupal exuviae (HEM) feeds and were characterized by an increase in the relative abundance of the Firmicutes familiesBacillaceae,Enterococcaceae, andLachnospiraceaeand the Actinobacteria familyActinomycetaceae, which all include taxa considered beneficial for fish health. Modulation of the digesta community by HEM was characterized by a sharp increase inPaenibacillusand a decrease of several Gammaproteobacteria and Bacteroidota members. In turn, a mealworm larvae-based diet (Tenebrio molitor, TM) had only a modest impact on microbiota composition. Further, using quantitative PCR, we demonstrate that shifts induced by HEM were accompanied by an increase in copy number of chitinase ChiA-encoding genes, predominantly originating fromPaenibacillusspecies with effective chitinolytic activity. Our study reveals an HEM-driven increase in chitin-degrading taxa and associated chitinolytic activity, uncovering potential benefits of adopting exuviae-supplemented diets, a waste product of insect rearing, as a functional ingredient.
Identification of Neutrophil-Related Factor LCN2 for Predicting Severity of Patients With Influenza A Virus and SARS-CoV-2 Infection
Authors: Huang Zhisheng , Li Hui , Liu Shuai , Jia Ju , Zheng Ying , Cao Bin
Published: April 2022

Background

Influenza and COVID-19 are respiratory infectious diseases that are characterized by high contagiousness and high mutation and pose a serious threat to global health. After Influenza A virus (IAV) and SARS-CoV-2 infection, severe cases may develop into acute lung injury. Immune factors act as an important role during infection and inflammation. However, the molecular immune mechanisms still remain unclear. We aimed to explore immune-related host factors and core biomarker for severe infection, to provide a new therapeutic target of host factor in patients.

Methods

Gene expression profiles were obtained from Gene Expression Omnibus and the Seurat R package was used for data process of single-cell transcriptome. Differentially expressed gene analysis and cell cluster were used to explore core host genes and source cells of genes. We performed Gene Ontology enrichment, Kyoto Encyclopedia of Genes and Genomes analysis, and gene set enrichment analysis to explore potential biological functions of genes. Gene set variation analysis was used to evaluate the important gene set variation score for different samples. We conduct Enzyme-linked immunosorbent assay (ELISA) to test plasma concentrations of Lipocalin 2 (LCN2).

Results

Multiple virus-related, cytokine-related, and chemokine-related pathways involved in process of IAV infection and inflammatory response mainly derive from macrophages and neutrophils. LCN2 mainly in neutrophils was significantly upregulated after either IAV or SARS-CoV-2 infection and positively correlated with disease severity. The plasma LCN2 of influenza patients were elevated significantly compared with healthy controls by ELISA and positively correlated with disease severity of influenza patients. Further bioinformatics analysis revealed that LCN2 involved in functions of neutrophils, including neutrophil degranulation, neutrophil activation involved in immune response, and neutrophil extracellular trap formation.

Conclusion

The neutrophil-related LCN2 could be a promising biomarker for predicting severity of patients with IAV and SARS-CoV-2 infection and may as a new treatment target in severe patients.
Dynamic Hybrid Flagellar Motors—Fuel Switch and More
Authors: Thormann Kai M.
Published: April 2022

Flagellar motors are intricate rotating nanomachines that are powered by transmembrane ion gradients. The stator complexes are the powerhouses of the flagellar motor: They convert a transmembrane ion gradient, mainly of H+ or Na+, into rotation of the helical flagellar filament. They are thus essential for motor function. The number of stators synchronously engaged in the motor is surprisingly dynamic and depends on the load and the environmental concentration of the corresponding coupling ion. Thus, the rotor–stator interactions determine an important part of the properties of the motor. Numerous bacteria have been identified as possessing more than one set of stators, and some species have been demonstrated to use these different stators in various configurations to modify motor functions by dynamic in-flight swapping. Here, we review knowledge of the properties, the functions, and the evolution of these hybrid motors and discuss questions that remain unsolved.
Eliciting Implicit Awareness in Alzheimer’s Disease and Mild Cognitive Impairment: A Task-Based Functional MRI Study
Authors: Tondelli Manuela , Benuzzi Francesca , Ballotta Daniela , Molinari Maria Angela , Chiari Annalisa , Zamboni Giovanna
Published: April 2022

Background

Recent models of anosognosia in dementia have suggested the existence of an implicit component of self-awareness about one’s cognitive impairment that may remain preserved and continue to regulate behavioral, affective, and cognitive responses even in people who do not show an explicit awareness of their difficulties. Behavioral studies have used different strategies to demonstrate implicit awareness in patients with anosognosia, but no neuroimaging studies have yet investigated its neural bases.

Methods

Patients with amnestic mild cognitive impairment and dementia due to Alzheimer’s disease underwent functional magnetic resonance imaging (fMRI) during the execution of a color-naming task in which they were presented with neutral, negative, and dementia-related words (Dementia-Related Emotional Stroop).

Results

Twenty-one patients were recruited: 12 were classified as aware and 9 as unaware according to anosognosia scales (based on clinical judgment and patient-caregiver discrepancy). Behavioral results showed that aware patients took the longest time to process dementia-related words, although differences between word types were not significant, limiting interpretation of behavioral results. Imaging results showed that patients with preserved explicit awareness had a small positive differential activation of the posterior cingulate cortex (PCC) for the dementia-related words condition compared to the negative words, suggesting attribution of emotional valence to both conditions. PCC differential activation was instead negative in unaware patients, i.e., lower for dementia-related words relative to negative-words. In addition, the more negative the differential activation, the lower was the Stroop effect measuring implicit awareness.

Conclusion

Posterior cingulate cortex preserved response to dementia-related stimuli may be a marker of preserved implicit self-awareness.
Aging-Related Vascular Inflammation: Giant Cell Arteritis and Neurological Disorders
Authors: Watanabe Ryu , Hashimoto Motomu
Published: April 2022

Aging is characterized by the functional decline of the immune system and constitutes the primary risk factor for infectious diseases, cardiovascular disorders, cancer, and neurodegenerative disorders. Blood vessels are immune-privileged sites and consist of endothelial cells, vascular smooth muscle cells, macrophages, dendritic cells, fibroblasts, and pericytes, among others. Aging also termed senescence inevitably affects blood vessels, making them vulnerable to inflammation. Atherosclerosis causes low-grade inflammation from the endothelial side; whereas giant cell arteritis (GCA) causes intense inflammation from the adventitial side. GCA is the most common autoimmune vasculitis in the elderly characterized by the formation of granulomas composed of T cells and macrophages in medium- and large-sized vessels. Recent studies explored the pathophysiology of GCA at unprecedented resolutions, and shed new light on cellular signaling pathways and metabolic fitness in wall-destructive T cells and macrophages. Moreover, recent reports have revealed that not only can cerebrovascular disorders, such as stroke and ischemic optic neuropathy, be initial or coexistent manifestations of GCA, but the same is true for dementia and neurodegenerative disorders. In this review, we first outline how aging affects vascular homeostasis. Subsequently, we review the updated pathophysiology of GCA and explain the similarities and differences between vascular aging and GCA. Then, we introduce the possible link between T cell aging, neurological aging, and GCA. Finally, we discuss therapeutic strategies targeting both senescence and vascular inflammation.
What and Where: Location-Dependent Feature Sensitivity as a Canonical Organizing Principle of the Visual System
Authors: Sedigh-Sarvestani Madineh , Fitzpatrick David
Published: April 2022

Traditionally, functional representations in early visual areas are conceived as retinotopic maps preserving ego-centric spatial location information while ensuring that other stimulus features are uniformly represented for all locations in space. Recent results challenge this framework of relatively independent encoding of location and features in the early visual system, emphasizing location-dependent feature sensitivities that reflect specialization of cortical circuits for different locations in visual space. Here we review the evidence for such location-specific encoding including: (1) systematic variation of functional properties within conventional retinotopic maps in the cortex; (2) novel periodic retinotopic transforms that dramatically illustrate the tight linkage of feature sensitivity, spatial location, and cortical circuitry; and (3) retinotopic biases in cortical areas, and groups of areas, that have been defined by their functional specializations. We propose that location-dependent feature sensitivity is a fundamental organizing principle of the visual system that achieves efficient representation of positional regularities in visual experience, and reflects the evolutionary selection of sensory and motor circuits to optimally represent behaviorally relevant information. Future studies are necessary to discover mechanisms underlying joint encoding of location and functional information, how this relates to behavior, emerges during development, and varies across species.
Molecular Hydrogen as a Medical Gas for the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Possible Efficacy Based on a Literature Review
Authors: Hirano Shin-ichi , Ichikawa Yusuke , Sato Bunpei , Takefuji Yoshiyasu , Satoh Fumitake
Published: April 2022

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disorder that is characterized by fatigue that persists for more than 6 months, weakness, sleep disturbances, and cognitive dysfunction. There are multiple possible etiologies for ME/CFS, among which mitochondrial dysfunction plays a major role in abnormal energy metabolism. The potential of many substances for the treatment of ME/CFS has been examined; however, satisfactory outcomes have not yet been achieved. The development of new substances for curative, not symptomatic, treatments is desired. Molecular hydrogen (H2) ameliorates mitochondrial dysfunction by scavenging hydroxyl radicals, the most potent oxidant among reactive oxygen species. Animal experiments and clinical trials reported that H2 exerted ameliorative effects on acute and chronic fatigue. Therefore, we conducted a literature review on the mechanism by which H2 improves acute and chronic fatigue in animals and healthy people and showed that the attenuation of mitochondrial dysfunction by H2 may be involved in the ameliorative effects. Although further clinical trials are needed to determine the efficacy and mechanism of H2 gas in ME/CFS, our literature review suggested that H2 gas may be an effective medical gas for the treatment of ME/CFS.
Virus-Induced Maternal Immune Activation as an Environmental Factor in the Etiology of Autism and Schizophrenia
Authors: Massrali Aïcha , Adhya Dwaipayan , Srivastava Deepak P. , Baron-Cohen Simon , Kotter Mark R.
Published: April 2022

Maternal immune activation (MIA) is mediated by activation of inflammatory pathways resulting in increased levels of cytokines and chemokines that cross the placental and blood-brain barriers altering fetal neural development. Maternal viral infection is one of the most well-known causes for immune activation in pregnant women. MIA and immune abnormalities are key players in the etiology of developmental conditions such as autism, schizophrenia, ADHD, and depression. Experimental evidence implicating MIA in with different effects in the offspring is complex. For decades, scientists have relied on either MIA models or human epidemiological data or a combination of both. MIA models are generated using infection/pathogenic agents to induce an immunological reaction in rodents and monitor the effects. Human epidemiological studies investigate a link between maternal infection and/or high levels of cytokines in pregnant mothers and the likelihood of developing conditions. In this review, we discuss the importance of understanding the relationship between virus-mediated MIA and neurodevelopmental conditions, focusing on autism and schizophrenia. We further discuss the different methods of studying MIA and their limitations and focus on the different factors contributing to MIA heterogeneity.
Tobacco and ADHD: A Role of MAO-Inhibition in Nicotine Dependence and Alleviation of ADHD Symptoms
Authors: Taylor Mairin Rose , Carrasco Kelly , Carrasco Andres , Basu Arindam
Published: April 2022

Attention-deficit/hyperactivity disorder (ADHD) is a relatively commonly occurring neurodevelopmental disorder affecting approximately 5% of children and young people. The neurobiological mechanisms of ADHD are proposed to particularly center around increased dopamine receptor availability related to associated symptoms of reduced attention regulation and impulsivity. ADHD is also persistent across the lifespan and associated with a raft of impulsive and health-risk behaviors including substance abuse and smoking. Research highlighting the potentially significant levels of monoamine oxidase (MAO) inhibitory properties in tobacco smoke and e-cigarettes may provide a mechanism for increased tobacco smoke dependence among those with ADHD, in addition to the role of nicotine.

Aim

This scoping review aimed to establish evidence for the above neurobiological pathway between smoking and ADHD symptom-alleviation or “self-medication” with the inclusion of the mechanism of MAO-inhibitors indirect increasing dopamine in the brain.

Methodology

Scoping review methodologies were employed in this review selected to synthesize multiple sources of empirical research to identify current gaps in the knowledge base and identify key characteristics of research data related to a phenomenon. Databases searched included OVID MEDLINE(R), Embase, Cochrane, PsycINFO and SCOPUS limited to 2000 onward and empirically validated, peer-reviewed research.

Findings

There is support for the role of MAO-inhibition on greater reinforcement of smoking for individuals with ADHD through a greater impact on dopaminergic availability than nicotine; potentially moderating ADHD symptoms.

Conclusion

Greater support for a “self-medication” model of ADHD and smoking includes not only nicotine but also MAO-inhibitors as dopamine agonists contained in cigarettes and e-cigarettes.