bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Short Peptidoglycan Recognition Protein PGLYRP1/Tag-7/PGRP-S Inhibits Listeria monocytogenes Intracellular Survival in Macrophages
Authors: Slonova Darya , Posvyatenko Alexandra , Kibardin Alexey , Sysolyatina Elena , Lyssuk Elena , Ermolaeva Svetlana , Obydennyi Sergei , Gnuchev Nikolay , Georgiev Georgii , Severinov Konstantin , Larin Sergey
Published: December 2020

PGLYRP1/Tag-7/PGRP-S is one of mammalian peptidoglycan recognition proteins (PGRPs). Here, we demonstrate that human recombinant PGLYRP1/Tag-7/PGRP-S potentiates the response of murine macrophage-like ANA-1 cells and human macrophages to facultative intracellular pathogen Listeria monocytogenes. PGLYRP1/Tag-7/PGRP-S binds to the surface of L. monocytogenes and other bacterial cells but has no effect on their growth in culture. While PGLYRP1/Tag-7/PGRP-S treatment modestly enhanced phagocytosis of bacteria by ANA-1 cells, the intracellular survival of PGLYRP1/Tag-7/PGRP-S treated L. monocytogenes was strongly inhibited 2 h after internalization. PGLYRP1/Tag-7/PGRP-S treatment of bacteria boosted oxidative burst induction and increased the level of proinflammatory cytokine IL-6 produced by ANA-1, however, these effects happened too late to be responsible for decreased intracellular survival of bacteria. Our results thus suggest that PGLYRP1/Tag-7/PGRP-S acts as a molecular sensor for detection of L. monocytogenes infection of mammalian cells that leads to increased killing through a mechanism(s) that remains to be defined.
Autophagy Receptor Tollip Facilitates Bacterial Autophagy by Recruiting Galectin-7 in Response to Group A Streptococcus Infection
Authors: Lin Ching-Yu , Nozawa Takashi , Minowa-Nozawa Atsuko , Toh Hirotaka , Hikichi Miyako , Iibushi Junpei , Nakagawa Ichiro
Published: December 2020

Bacterial autophagy—a type of macroautophagy that is also termed xenophagy—selectively targets intracellular bacteria such as group A Streptococcus (GAS), a ubiquitous pathogen that causes numerous serious diseases, including pharyngitis, skin infections, and invasive life-threatening infections. Although bacterial autophagy is known to eliminate invading bacteria via the action of autophagy receptors, the underlying mechanism remains unclear. Herein, we elucidated that Tollip functions as a bacterial-autophagy receptor in addition to participating involved in the intracellular immunity mechanism that defends against bacterial infection. Tollip was recruited to GAS-containing endosomal vacuoles prior to the escape of GAS into the cytosol; additionally, Tollip knockout disrupted the recruitment of other autophagy receptors, such as NBR1, TAX1BP1, and NDP52, to GAS-containing autophagosomes and led to prolonged intracellular survival of GAS. Furthermore, Tollip was found to be required for the recruitment of galectin-1 and -7 to GAS-containing autophagosomes, and immunoprecipitation results indicated that Tollip interacts with galectin-7. Lastly, our data also revealed that galectin-1 and -7 are involved in the restriction of GAS replication in cells. These results demonstrated that Tollip modulates bacterial autophagy by recruiting other autophagy receptors and galectins.
Trimethylamine N-Oxide Was Not Associated With 30-Day Left Ventricular Systolic Dysfunction in Patients With a First Anterior ST-Segment Elevation Myocardial Infarction After Primary Revascularization: A Sub-analysis From an Optical Coherence Tomography Registry
Authors: Zhou Jinying , Yu Shiqin , Tan Yu , Zhou Peng , Liu Chen , Sheng Zhaoxue , Li Jiannan , Chen Runzhen , Zhao Shihua , Yan Hongbing
Published: December 2020

Objective: Left ventricular systolic dysfunction (LVSD) after ST-segment elevation myocardial infarction (STEMI) is associated with poor outcome. Trimethylamine N-oxide (TMAO), a gut metabolite, is linked to cardiovascular diseases but its relationship with LVSD after STEMI remains unclear. The present study therefore aimed to investigate the relationship between TMAO and LVSD at 30 days after a first anterior STEMI.

Methods: This was a sub-study from the OCTAMI (Optical Coherence Tomography Examination in Acute Myocardial Infarction) registry. Eligible patients were included in current study if they: (1) presented with a first anterior STEMI; (2) had available baseline TMAO concentration; (3) completed a cardiovascular magnetic resonance examination at 30 days after STEMI. LVSD was defined as left ventricular ejection fraction < 50%. Associations between TMAO and left ventricular ejection fraction, infarct size and left ventricular global strain were examined.

Results: In total, 78 patients were included in final analysis. Overall, TMAO was moderately associated with peak cTnI (r = 0.27, p = 0.01), age (r = 0.34, p < 0.01), and estimated glomerular filtration rate (r = −0.30, p < 0.01). At 30-day follow-up, 41 patients were in the LVSD group and 37 in the non-LVSD group. Baseline TMAO levels were not significantly different between the two groups (LVSD vs. non-LVSD: median 1.9 μM, 25−75th percentiles 1.5–3.3 μM vs. median 1.9 μM, 25−75th percentiles 1.5–2.7 μM; p = 0.46). Linear regression analyses showed that TMAO was not associated with left ventricular ejection fraction, infarct size or left ventricular global strain at 30 days (all p > 0.05).

Conclusions: TMAO was not significantly correlated with 30-day LVSD in patients with a first anterior STEMI after primary revascularization.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03593928.
The Impact of COVID-19 on Neurology Education: A Medical Student Perspective
Authors: Guadix Sergio W. , Sha Carrie , Sandrone Stefano , Safdieh Joseph E. , Sarva Harini
Published: December 2020

The COVID-19 pandemic has fundamentally altered the pre-clerkship, clerkship, and research experiences for medical students. Although these changes impact all specialties, we highlight the unique challenges faced by neurology education and discuss methods by which our institution is adapting to these changes at the epicenter of the pandemic in the U.S. We include a few examples of how some neurology departments around the country have altered their teaching methods in the COVID-19 era and capitalize on lessons learned by proposing new strategies for moving neurology education forward.
Diabetes in Patients With Pancreatic Neuroendocrine Neoplasms
Authors: Zhuge Xiaoling , Wang Yajie , Chen Xiao , Guo Chuangen
Published: December 2020

Objective

Diabetes mellitus (DM) is probably a risk factor for pancreatic neuroendocrine neoplasms (PNENs). However, the prevalence of DM in PNEN patients remains inconclusive. In the present study we observed the prevalence of DM and possible risk factors in PNEN patients.

Methods

After excluding those with insulinoma, a total of 197 patients with PNENs were included. The demographic data, pathological characteristics, and data of blood biochemical tests were recorded. DM was considered if there was evidence of a fasting plasma glucose level of ≥7.0 mmol/L or a 2-h plasma glucose level of ≥11.1 mmol/L, or a history of DM at the time of PNEN diagnosis. Impaired fasting glucose was considered if fasting plasma glucose level was between 6.1 and 7.0 mmol/L.

Results

The prevalence of DM, new-onset DM, and impaired fasting glucose were 17.26, 9.14, and 7.1%, respectively. The prevalence of DM was 26.0% in patients ≥60 years old (19/73) and 12.1% in patients <60 years old. Multivariable logistic regression analysis demonstrated that age, tumor size, and nerve invasion were independent risk factors for DM and impaired fasting glucose + DM (p < 0.05). Age, organs and nerve invasion were independent risk factors for impaired fasting glucose. Low high-density lipoprotein (HDL) was also a risk factor for incident of DM (OR = 0.15, 95%CI: 0.03–0.66). G2/G3 was an independent risk factor for DM in women.

Conclusion

Our data shows that the prevalence of DM is 17.26% in patients with PNENs and is 26.0% in patients ≥60 years of age after excluding insulinoma. Age, nerve invasion, tumor size, and HDL are risk factors for DM in PNEN patients.
Optimal Design of a Hybrid Energy System for the Supply of Clean and Stable Energy to Offshore Installations
Authors: Riboldi Luca , Alves Erick F. , Pilarczyk Marcin , Tedeschi Elisabetta , Nord Lars O.
Published: December 2020

This paper presents an innovative hybrid energy system for stable power and heat supply in offshore oil and gas installations. The proposed concept integrates offshore wind power, onsite gas turbines and an energy storage system based on fuel cell and electrolyzer stacks. It is expected to be an effective option to decarbonize the offshore petroleum sector as it allows a more extensive exploitation of the offshore wind resource by means of energy storage. To ascertain its potential, an integrated model was developed. The integrated model allows to simulate the process and electric grid performances. The inclusion of both domains provides a comprehensive picture of a given design operational performance. The feasibility of the proposed concept was first investigated through a parametric analysis where an understanding of its potential and limitations was gained. A rigorous optimization was then implemented to identify the designs resulting in the best performances and ultimately to obtain a comprehensive picture of the suitability of the concept. It is shown that a well-designed system can reduce carbon emissions compared, not only to a standard concept based on gas turbines (almost 1,300 kt less CO2emissions, making up for a relative 36% reduction), but also to the integration of a wind farm alone (more than 70 kt less CO2emissions, making up for a relative 3% reduction, but complying with grid dynamics requirements). Moreover, the energy storage system brings benefits to the electric grid stability and allows the integration of large wind power capacity without overpassing the 2% maximum frequency variation (as it is the case without energy storage). Not least, the optimization showed that the definition of an optimal design is a complex task, with little margin to further gains in terms of carbon emissions, likely due to technological limitations.
Environmental and Biological Determinants of Algal Lipids in Western Arctic and Subarctic Seas
Authors: Marmillot Vincent , Parrish Christopher C. , Tremblay Jean-Éric , Gosselin Michel , MacKinnon Jenna F.
Published: December 2020

The Arctic is undergoing numerous environmental transformations. As a result of rising temperatures and additional freshwater inputs, ice cover is changing, with profound impacts on organisms at the base of food webs and consequently on the entire Arctic ecosystem. Indeed, phytoplankton not only provide energy as lipids, but also essential fatty acids (EFA) that animals cannot synthesize and must acquire in their diet. Omega-3 (ω3) and omega-6 (ω6) polyunsaturated fatty acids (PUFA) are essential for the healthy development and function of organisms. The high energy potential of monounsaturated fatty acids (MUFA) is of particular importance in cold waters, and various fatty acids including saturated fatty acids (SFA) are involved in organismal responses to environmental stressors. Yet relatively little is known of how variability or change in physicochemical seawater properties (e.g., temperature, light, salinity, pH and nutrients) may affect lipid synthesis in polar environments, either directly, by altering algal physiology, or indirectly, by promoting shifts in phytoplankton species composition. Here we investigated these two possibilities by sampling along a 3,000-km transect spanning 28 degrees of latitude across the subarctic and Arctic domains of Canada. The taxonomic composition of phytoplankton mainly drove the FA profiles measured in particulate organic matter (POM). Strong, positive correlations between 16:1ω7 and diatoms were observed while the proportion of PUFA and ω6 FA increased with flagellate abundance. Among specific FAs, eicosapentaenoic acid (EPA; 20:5ω3) was positively correlated with diatoms but the expected relationship between docosahexaenoic acid (DHA; 22:6ω3) and dinoflagellates was not observed. Decreasing pH had a negative effect on EPA and MUFA proportions, and DHA proportions tended to decrease with higher temperature. These two effects were primarily driven by differences in phytoplankton assemblage composition. Overall, the results of this geographically extensive study provide new information into the use of lipid markers and the ecological determinants of FA synthesis in the North. It also highlights the importance of long-lived subsurface chlorophyll maximum layers in supplying PUFA-rich POM to the food web and suggests that this situation may persist despite ongoing changes in the physical environment.
Mitigation of Odor, NH3, H2S, GHG, and VOC Emissions With Current Products for Use in Deep-Pit Swine Manure Storage Structures
Authors: Chen Baitong , Koziel Jacek A. , Banik Chumki , Ma Hantian , Lee Myeongseong , Wi Jisoo , Meiirkhanuly Zhanibek , O'Brien Samuel C. , Li Peiyang , Andersen Daniel S. , Białowiec Andrzej , Parker David B.
Published: December 2020

Odorous gas emissions from swine production have been a concern for neighbors and communities near livestock farms. Manure storage is one of the main sources of gaseous emissions. Manure additive products are marketed as a simple solution to this environmental challenge. Manure additives are user-friendly for producers and can be applied (e.g., periodically poured into manure) without changing the current manure storage structure. Little scientific data exist on how these products perform in mitigating gaseous emissions from swine manure. The research objective was to evaluate the effectiveness of 12 marketed manure additives on mitigating odor, ammonia (NH3), hydrogen sulfide (H2S), greenhouse gases (GHG), and odorous volatile organic compounds (VOCs) from stored swine manure. A controlled pilot-scale setup was used to conduct 8-week long trials using manufacturer-prescribed dosages of additives into swine manures. Manure was outsourced from three swine farms to represent a variety of manure storage types and other factors affecting the properties. Measured gaseous emissions were compared between the treated and untreated manure. None of the tested products showed a significant reduction in gaseous emissions when all (n = 3) manures were treated as replicates. Selected products showed a wide range of statistically-significant reduction and generation of gaseous emissions when emissions were compared in pairs of manure types from one farm. The latter observation highlighted the lack of consistent mitigation of gaseous emissions by manure additives. The results of this study do not warrant full-scale trials with the tested products.
Convergent Evolution of Locomotory Modes in Euarchontoglires
Authors: Geng Wei-hang , Wang Xiao-ping , Che Li-feng , Wang Xin , Liu Rui , Zhou Tong , Roos Christian , Irwin David M. , Yu Li
Published: December 2020

The research of phenotypic convergence is of increasing importance in adaptive evolution. Locomotory modes play important roles in the adaptive evolution of species in the Euarchontoglires, however, the investigation of convergent evolution of the locomotory modes across diverse Euarchontoglire orders is incomplete. We collected measurements of three phalangeal indices of manual digit III, including metacarpal of digit III (MC3), manus proximal phalanx of digit III (MPP3), and manus intermediate phalanx of digit III (MIP3), from 203 individuals of 122 Euarchontoglires species representing arboreal (orders Scandentia, Rodentia, and Primates), terrestrial (orders Scandentia and Rodentia), and gliding (orders Dermoptera and Rodentia) locomotory modes. This data can be separated into seven groups defined by order and locomotory mode. Based on combination of the three phalangeal indices, the Principle component analyses (PCA), phylomorphospace plot, and C-metrics analyses clustered the arboreal species of Scandentia, Rodentia, and Primates together and the terrestrial species of Scandentia and Rodentia together, showing the convergent signal in evolution of the arboreal (C1 = 0.424,P< 0.05) and terrestrial (C1 = 0.560,P< 0.05) locomotory modes in Euarchontoglires. Although the gliding species from Dermoptera and Rodentia did not cluster together, they also showed the convergent signal (C1 = 0.563,P< 0.05). Our work provides insight into the convergent evolution of locomotory modes in Euarchontoglires, and reveals that these three indices contribute valuable information to identify convergent evolution in Euarchontoglires.
Physical Characterization of Colorectal Cancer Spheroids and Evaluation of NK Cell Infiltration Through a Flow-Based Analysis
Authors: Sargenti Azzurra , Musmeci Francesco , Bacchi Francesco , Delprete Cecilia , Cristaldi Domenico Andrea , Cannas Federica , Bonetti Simone , Pasqua Simone , Gazzola Daniele , Costa Delfina , Villa Federico , Zocchi Maria Raffaella , Poggi Alessandro
Published: December 2020

To improve pathogenetic studies in cancer development and reliable preclinical testing of anti-cancer treatments, three-dimensional (3D) cultures, including spheroids, have been widely recognized as more physiologically relevant in vitro models of in vivo tumor behavior. Currently, the generation of uniformly sized spheroids is still challenging: different 3D cell culture methods produce heterogeneous populations in dimensions and morphology, that may strongly influence readouts reliability correlated to tumor growth rate or antitumor natural killer (NK) cell-mediated cytotoxicity. In this context, an increasing consensus claims the integration of microfluidic technologies within 3D cell culture, as the physical characterization of tumor spheroids is unavoidably demanded to standardize protocols and assays for in vitro testing. In this paper, we employed a flow-based method specifically conceived to measure weight, size and focused onto mass density values of tumor spheroids. These measurements are combined with confocal and digital imaging of such samples. We tested the spheroids of four colorectal cancer (CRC) cell lines that exhibit statistically relevant differences in their physical characteristics, even though starting from the same cell seeding density. These variations are seemingly cell line-dependent and associated with the number of growing cells and the degree of spheroid compaction as well, supported by different adenosine-triphosphate contents. We also showed that this technology can estimate the NK cell killing efficacy by measuring the weight loss and diameter shrinkage of tumor spheroids, alongside with the commonly used cell viability in vitro test. As the activity of NK cells relies on their infiltration rate, the in vitro sensitivity of CRC spheroids proved to be exposure time- and cell line-dependent with direct correlation to the cell viability reduction. All these functional aspects can be measured by the system and are documented by digital image analysis. In conclusion, this flow-based method potentially paves the way towards standardization of 3D cell cultures and its early adoption in cancer research to test antitumor immune response and set up new immunotherapy strategies.
Environmental Factor-Mediated Transgenerational Inheritance of Igf2r Hypomethylation and Pulmonary Allergic Response via Targeting Dendritic Cells
Authors: Suen Jau-Ling , Wu Tai-Ting , Li Yue-Hyuan , Lee Chin-Lai , Kuo Fu-Chen , Yan Pearlly S. , Wu Chia-Fang , Tran Mita , Wang Chien-Jen , Hung Chih-Hsing , Wu Ming-Tsang , Chan Michael W. Y. , Huang Shau-Ku
Published: December 2020

The developmental origin of allergic diseases has been suggested, but the molecular basis remains enigmatic. Exposure to environmental factors, such as di-(2-ethylhexyl) phthalate (DEHP; a common plasticizer), is suggested to be associated with increased childhood allergic asthma, but the causal relationship and its underlying mechanism remain unknown. This study explored the transgenerational mechanism of DEHP on allergic asthma and dendritic cell (DC) homeostasis through epigenetic modification. In a murine model, ancestral exposure of C57BL/6 mice to low-dose DEHP led to trans-generational promoter hypomethylation of the insulin-like growth factor 2 receptor (Igf2r), concomitant with enhanced Igf2r expression and increased apoptosis prominently in CD8α+ DCs upon ligand stimulation, with consequent reduction in their IL-12 secretion and subsequent T cell-derived IFN-γ, thereby promoting a default Th2-associated pulmonary allergic response. Increased apoptosis was also noted in circulating IGF2Rhigh human DCs. Further, in human placenta, the methylation level at the orthologous IGF2R promoter region was shown to be inversely correlated with the level of maternal DEHP intake. These results support the importance of ancestral phthalate exposure in conferring the trans-generational risk of allergic phenotypes, featuring hypo-methylation of the IGF2R gene and dysregulated DC homeostasis.
Vaccine-Induced CD8+ T Cell Responses in Children: A Review of Age-Specific Molecular Determinants Contributing to Antigen Cross-Presentation
Authors: Beijnen Elisabeth M. S. , van Haren Simon D.
Published: December 2020

Infections are most common and most severe at the extremes of age, the young and the elderly. Vaccination can be a key approach to enhance immunogenicity and protection against pathogens in these vulnerable populations, who have a functionally distinct immune system compared to other age groups. More than 50% of the vaccine market is for pediatric use, yet to date vaccine development is often empiric and not tailored to molecular distinctions in innate and adaptive immune activation in early life. With modern vaccine development shifting from whole-cell based vaccines to subunit vaccines also comes the need for formulations that can elicit a CD8+T cell response when needed, for example, by promoting antigen cross-presentation. While our group and others have identified many cellular and molecular determinants of successful activation of antigen-presenting cells, B cells and CD4+T cells in early life, much less is known about the ontogeny of CD8+T cell induction. In this review, we summarize the literature pertaining to the frequency and phenotype of newborn and infant CD8+T cells, and any evidence of induction of CD8+T cells by currently licensed pediatric vaccine formulations. In addition, we review the molecular determinants of antigen cross-presentation on MHC I and successful CD8+T cell induction and discuss potential distinctions that can be made in children. Finally, we discuss recent advances in development of novel adjuvants and provide future directions for basic and translational research in this area.
Evaluation of Two Chemiluminescent and Three ELISA Immunoassays for the Detection of SARS-CoV-2 IgG Antibodies: Implications for Disease Diagnosis and Patients’ Management
Authors: Speletas Matthaios , Kyritsi Maria A. , Vontas Alexandros , Theodoridou Aikaterini , Chrysanthidis Theofilos , Hatzianastasiou Sophia , Petinaki Efthimia , Hadjichristodoulou Christos
Published: December 2020

The estimation of anti-SARS-CoV-2 IgG antibodies is possibly the best approach to accurately establish the number of infected individuals and the seroprevalence of COVID-19 within a population. Thus, several commercial immunoassays have recently been developed. The purpose of our study was to assess the performance of five commonly used immunoassays in Greece (3 ELISA, namely Euroimmun SARS-CoV-2, GA GENERIC SARS-CoV-2 and Vircell COVID-19; and 2 chemiluminescent, namely ABBOTT SARS-CoV-2 and ROCHE Elecsys Anti-SARS-CoV-2 test) for the detection of anti-SARS-CoV-2 IgG antibodies. Sera specimens derived from 168 individuals were utilized to assess the specificity and sensitivity score of each assay. Among them, we included 99 COVID-19 patients (29 asymptomatic, 36 with symptom onset 4 to 14 days before serum sampling, and 34 with symptom initiation ≥ 15 days ago), and 69 volunteers with sera specimens collected prior to the SARS-CoV-2 outbreak and maintained at −80°C. We demonstrated that chemiluminescent immunoassays exhibit a significantly higher specificity score but a lower sensitivity, compared to ELISA immunoassays. Moreover, immunoassays detecting IgG antibodies against SARS-CoV-2 N protein instead of S protein alone are more reliable, considering both specificity and sensitivity scores. Interestingly, all asymptomatic patients displayed anti-SARS-CoV-2 IgG antibodies, confirmed by at least two immunoassays. We suggest that chemiluminescent assays could be used as screening methods for the detection of anti-SARS-CoV-2 antibodies to evaluate the possible prevalence of disease in the general population, while ELISA assays would be more reliable to evaluate, and follow-up confirmed COVID-19 patients.
Numerical Simulation of Inline Forces on a Bottom-Mounted Circular Cylinder Under the Action of a Specific Freak Wave
Authors: Wang Yuqi , Xu Fuyou , Zhang Zhanbiao
Published: December 2020

Freak waves pose a great threat to the tension-leg platforms (TLPs) and monopile foundations of offshore wind turbines (OWTs), which necessitates comprehensive investigations on the characteristics of freak waves and the wave actions on those offshore renewable energy structures with circular cylinder. The recorded freak wave series “New Year Wave” (NYW) was numerically simulated using the Computational Fluid Dynamics methods. The compensation measure was adopted to effectively improve simulation accuracy. Under the action of the NYW, the inline forces and secondary load cycle (SLC) on a vertical-mounted cylinder, as the classic form for the TLPs and foundation of OWTs, were fully addressed. The simulation results were compared with the empirical formulations and experimental data to reveal the differences and the possible causes. The development of SLC was found to be closely related to the downstream vortex and return flow, which induces the reduction of the wall pressure and thus the inline force. The maximum inline forces vary with the cylinder position relative to the wave peak, and the simulation results reveal that the linear inline forces calculated by Morison formulation may be less than 65% of the total wave forces.
Determining the Distribution of Fluorescent Organic Matter in the Indian Ocean Using in situ Fluorometry
Authors: Shigemitsu Masahito , Uchida Hiroshi , Yokokawa Taichi , Arulananthan K. , Murata Akihiko
Published: December 2020

In order to determine the dynamics of marine fluorescent organic matter (FOM) using high-resolution spatial data,in situfluorometers have been used in the open ocean. In this study, we measured FOM during the Global Ocean Ship-based Hydrographic Investigations Program (GO-SHIP) expedition from early December 2019 to early February 2020, using anin situfluorometer at 148 stations along the two meridional transects (at ∼80 and ∼57°E) in the Indian Ocean, covering latitudinal ranges from ∼6°N to ∼20°S and ∼30 to ∼65°S, respectively. The FOM data obtained from the fluorometer were corrected for known temperature dependence and calibrated using FOM data measured onboard by a benchtop fluorometer. Using the relative water mass proportions estimated from water mass analyses, we determined the intrinsic values of FOM and apparent oxygen utilization (AOU) for each of the 12 water masses observed. We then estimated the basin-scale relationship between the intrinsic FOM and the AOU, as well as the turnover time for FOM in the Indian Ocean (410 ± 19 years) in combination with the microbial respiration rate in the dark ocean (>200 m). Consistent to previous estimates in the global tropical and subtropical ocean, the FOM turnover time obtained is of the same order of magnitude as the circulation age of the Indian Ocean, indicating that the FOM is refractory and is a sink for reduced carbon in the dark ocean. A decoupling of FOM and AOU from the basin-scale relationship was also observed in the abyssal waters of the northern Indian Ocean. The local variability may be explained by the effect of sinking organic matter altered by denitrification through the oxygen-deficient zone on enhanced abyssal FOM production relative to oxygen consumption.
Characterization of Metagenome-Assembled Genomes and Carbohydrate-Degrading Genes in the Gut Microbiota of Tibetan Pig
Authors: Zhou Saisai , Luo Runbo , Gong Ga , Wang Yifei , Gesang Zhuoma , Wang Kai , Xu Zhuofei , Suolang Sizhu
Published: December 2020

Tibetan pig is an important domestic mammal, providing products of high nutritional value for millions of people living in the Qinghai-Tibet Plateau. The genomes of mammalian gut microbiota encode a large number of carbohydrate-active enzymes, which are essential for the digestion of complex polysaccharides through fermentation. However, the current understanding of microbial degradation of dietary carbohydrates in the Tibetan pig gut is limited. In this study, we produced approximately 145 gigabases of metagenomic sequence data for the fecal samples from 11 Tibetan pigs. De novo assembly and binning recovered 322 metagenome-assembled genomes taxonomically assigned to 11 bacterial phyla and two archaeal phyla. Of these genomes, 191 represented the uncultivated microbes derived from novel prokaryotic taxa. Twenty-three genomes were identified as metagenomic biomarkers that were significantly abundant in the gut ecosystem of Tibetan pigs compared to the other low-altitude relatives. Further, over 13,000 carbohydrate-degrading genes were identified, and these genes were more abundant in some of the genomes within the five principal phyla: Firmicutes, Bacteroidetes, Spirochaetota, Verrucomicrobiota, and Fibrobacterota. Particularly, three genomes representing the uncultivated Verrucomicrobiota encode the most abundant degradative enzymes in the fecal microbiota of Tibetan pigs. These findings should substantially increase the phylogenetic diversity of specific taxonomic clades in the microbial tree of life and provide an expanded repertoire of biomass-degrading genes for future application to microbial production of industrial enzymes.
Therapeutic Efficacy of a Trichinella Spiralis Paramyosin-Derived Peptide Modified With a Membrane-Targeting Signal in Mice With Antigen-Induced Arthritis
Authors: Chen Yi , Shao Shuai , Huang Jingjing , Gu Yuan , Cheng Yuli , Zhu Xinping
Published: December 2020

Helminth-derived molecules have the ability to modulate the host immune system. Our previous study identified a tetradecapeptide derived from Trichinella spiralis paramyosin (Ts-pmy) that could bind to human complement component C9 to inhibit its polymerization, making the peptide a candidate therapeutic agent for complement-related immune disorders. Here, the peptide underwent an N-terminal modification with a membrane-targeting signal (a unique myristoylated peptide) to improve its therapeutic efficacy. We found that the modified peptide had a binding affinity to human C9 that was similar to that of the original peptide, as confirmed by microscale thermophoresis assays. The binding of the modified peptide to human C9 resulted in the inhibition of C9-related complement activation, as reflected by the decreased Zn2+-induced C9 polymerization and the decreased C9-dependent lysis of rabbit erythrocytes. In addition, the original and modified peptides could both bind to recombinant mouse C9 and inhibit the C9-dependent lysis of rabbit erythrocytes in normal mouse serum (NMS), which meant that the peptides could cross the species barrier to inhibit complement activity in mice. Further in vitro and in vivo analyses confirmed that the peptide modification increased the retention time of the peptide. Furthermore, intraarticular injection of the modified peptide markedly ameliorated knee swelling and joint damage in mice with antigen-induced arthritis (AIA), as assessed histologically. These results suggested that the Ts-pmy-derived peptide modified with a membrane-targeting signal was a reasonable candidate therapeutic agent for membrane attack complex (MAC)-related diseases [such as rheumatoid arthritis (RA)] and the study presented a new modification method to improve the potential therapeutic effects of the peptide.
Comparative Methylome Analysis of Campylobacter jejuni Strain YH002 Reveals a Putative Novel Motif and Diverse Epigenetic Regulations of Virulence Genes
Authors: Ghatak Sandeep , Armstrong Cheryl M. , Reed Sue , He Yiping
Published: December 2020

Campylobacter jejuni is a major cause of foodborne gastroenteritis worldwide inflicting palpable socioeconomic costs. The ability of this pathogen to successfully infect its hosts is determined not only by the presence of specific virulence genes but also by the pathogen’s capacity to appropriately regulate those virulence genes. Therefore, DNA methylation can play a critical role in both aspects of this process because it serves as both a means to protect the integrity of the cellular DNA from invasion and as a mechanism to control transcriptional regulation within the cell. In the present study we report the comparative methylome data of C. jejuni YH002, a multidrug resistant strain isolated from retail beef liver. Investigation into the methylome identified a putative novel motif (CGCGA) of a type II restriction-modification (RM) system. Comparison of methylomes of the strain to well-studied C. jejuni strains highlighted non-uniform methylation patterns among the strains though the existence of the typical type I and type IV RM systems were also observed. Additional investigations into the existence of DNA methylation sites within gene promoters, which may ultimately result in altered levels of transcription, revealed several virulence genes putatively regulated using this mode of action. Of those identified, a flagella gene (flhB), a RNA polymerase sigma factor (rpoN), a capsular polysaccharide export protein (kpsD), and a multidrug efflux pump were highly notable.
The Cognitive Profile of Mild Cognitive Impairment Due to Dementia With Lewy Bodies—An Updated Review
Authors: Hemminghyth Mathilde Suhr , Chwiszczuk Luiza Jadwiga , Rongve Arvid , Breitve Monica Haraldseid
Published: December 2020

Objective: Dementia with Lewy Bodies (DLB) is the second most common type of neurodegenerative dementia. Yet, the domain-specific cognitive impairment of the mild cognitive impairment (MCI) phase of this disease (DLB-MCI) is still not been established. This article gives an updated review on the neuropsychological profile of DLB-MCI, building on the findings from a previous review.

Methods: We performed systematic review and searched five different electronic databases (Scopus, Cochrane, EMBASE, MEDLINE, and PsycINFO) in May 2020 based on a PICO scheme. Our search was then restricted to articles published in 2019 and 2020. Ending up with a total of 90 articles to be reviewed by abstract and/or full text.

Results: In total four papers were included, whereof only one met our full inclusion criteria. Despite a substantial heterogeneity, our findings indicate that DLB-MCI patients have a pattern of executive, visuospatial, and attentional deficits.

Conclusion: The findings indicate that the neuropsychological profile of DLB-MCI is characterized by executive, visuospatial, and attentional deficits. Furthermore, the shortage of studies clearly underlines the paucity of published research into DLB-MCI and emphasizes the need for well-controlled studies.
Detecting Changes and Avoiding Catastrophic Forgetting in Dynamic Partially Observable Environments
Authors: Dick Jeffery , Ladosz Pawel , Ben-Iwhiwhu Eseoghene , Shimadzu Hideyasu , Kinnell Peter , Pilly Praveen K. , Kolouri Soheil , Soltoggio Andrea
Published: December 2020

The ability of an agent to detect changes in an environment is key to successful adaptation. This ability involves at least two phases: learning a model of an environment, and detecting that a change is likely to have occurred when this model is no longer accurate. This task is particularly challenging in partially observable environments, such as those modeled with partially observable Markov decision processes (POMDPs). Some predictive learners are able to infer the state from observations and thus perform better with partial observability. Predictive state representations (PSRs) and neural networks are two such tools that can be trained to predict the probabilities of future observations. However, most such existing methods focus primarily on static problems in which only one environment is learned. In this paper, we propose an algorithm that uses statistical tests to estimate the probability of different predictive models to fit the current environment. We exploit the underlying probability distributions of predictive models to provide a fast and explainable method to assess and justify the model's beliefs about the current environment. Crucially, by doing so, the method can label incoming data as fitting different models, and thus can continuously train separate models in different environments. This new method is shown to prevent catastrophic forgetting when new environments, or tasks, are encountered. The method can also be of use when AI-informed decisions require justifications because its beliefs are based on statistical evidence from observations. We empirically demonstrate the benefit of the novel method with simulations in a set of POMDP environments.
Reproducing Five Motor Behaviors in a Salamander Robot With Virtual Muscles and a Distributed CPG Controller Regulated by Drive Signals and Proprioceptive Feedback
Authors: Knüsel Jérémie , Crespi Alessandro , Cabelguen Jean-Marie , Ijspeert Auke J. , Ryczko Dimitri
Published: December 2020

Diverse locomotor behaviors emerge from the interactions between the spinal central pattern generator (CPG), descending brain signals and sensory feedback. Salamander motor behaviors include swimming, struggling, forward underwater stepping, and forward and backward terrestrial stepping. Electromyographic and kinematic recordings of the trunk show that each of these five behaviors is characterized by specific patterns of muscle activation and body curvature. Electrophysiological recordings in isolated spinal cords show even more diverse patterns of activity. Using numerical modeling and robotics, we explored the mechanisms through which descending brain signals and proprioceptive feedback could take advantage of the flexibility of the spinal CPG to generate different motor patterns. Adapting a previous CPG model based on abstract oscillators, we propose a model that reproduces the features of spinal cord recordings: the diversity of motor patterns, the correlation between phase lags and cycle frequencies, and the spontaneous switches between slow and fast rhythms. The five salamander behaviors were reproduced by connecting the CPG model to a mechanical simulation of the salamander with virtual muscles and local proprioceptive feedback. The main results were validated on a robot. A distributed controller was used to obtain the fast control loops necessary for implementing the virtual muscles. The distributed control is demonstrated in an experiment where the robot splits into multiple functional parts. The five salamander behaviors were emulated by regulating the CPG with two descending drives. Reproducing the kinematics of backward stepping and struggling however required stronger muscle contractions. The passive oscillations observed in the salamander's tail during forward underwater stepping could be reproduced using a third descending drive of zero to the tail oscillators. This reduced the drag on the body in our hydrodynamic simulation. We explored the effect of local proprioceptive feedback during swimming and forward terrestrial stepping. We found that feedback could replace or reduce the need for different drives in both cases. It also reduced the variability of intersegmental phase lags toward values appropriate for locomotion. Our work suggests that different motor behaviors do not require different CPG circuits: a single circuit can produce various behaviors when modulated by descending drive and sensory feedback.
Chronic Tear Deficiency Sensitizes Transient Receptor Potential Vanilloid 1-Mediated Responses in Corneal Sensory Nerves
Authors: Masuoka Takayoshi , Yamashita Yuka , Nakano Katsuya , Takechi Kenshi , Niimura Takahiro , Tawa Masashi , He Qiang , Ishizawa Keisuke , Ishibashi Takaharu
Published: December 2020

Chronic tear deficiency enhances the excitability of corneal cold-sensitive nerves that detect ocular dryness, which can lead to discomfort in patients with dry eye disease (DED). However, changes in corneal nerve excitations through the polymodal nociceptor “transient receptor potential vanilloid 1” (TRPV1) and the potential link between this receptor and symptoms of DED remain unclear. In this study, we examined the firing properties of corneal cold-sensitive nerves expressing TRPV1 and possible contributions of chronic tear deficiency to corneal nerve excitability by TRPV1 activation. The bilateral excision of lacrimal glands in guinea pigs decreased the tear volume and increased the frequency of spontaneous eyeblinks 1–4 weeks after surgery. An analysis of the firing properties of the cold-sensitive nerves was performed by single-unit recordings of corneal preparations 4 weeks after surgery in both the sham-operated and gland-excised groups. Perfusion of the TRPV1 agonist, capsaicin (1 μM), transiently increased the firing frequency in approximately 46–48% of the cold-sensitive nerves characterized by low-background activity and high threshold (LB-HT) cold thermoreceptors in both groups. Gland excision significantly decreased the latency of capsaicin-induced firing in cold-sensitive nerves; however, its magnitude was unchanged. Calcium imaging of cultured trigeminal ganglion neurons from both groups showed that intracellular calcium elevation of corneal neurons induced by a low concentration of capsaicin (0.03 μM) was significantly larger in the gland excision group, regardless of responsiveness to cold. An immunohistochemical study of the trigeminal ganglion revealed that gland excision significantly increased the proportion of corneal neurons enclosed by glial fibrillary acidic protein (GFAP)-immunopositive satellite glial cells. Topical application of the TRPV1 antagonist, A784168 (30 μM), on the ocular surface attenuated eye-blink frequency after gland excision. Furthermore, gland excision enhanced blink behavior induced by a low concentration of capsaicin (0.1 μM). These results suggest that chronic tear deficiency sensitizes the TRPV1-mediated response in the corneal LB-HT cold thermoreceptors and cold-insensitive polymodal nociceptors, which may be linked to dry eye discomfort and hyperalgesia resulting from nociceptive stimuli in aqueous-deficient dry eyes.
Neural Interactions in Developing Rhythmogenic Spinal Networks: Insights From Computational Modeling
Authors: Shevtsova Natalia A. , Ha Ngoc T. , Rybak Ilya A. , Dougherty Kimberly J.
Published: December 2020

The mechanisms involved in generation of rhythmic locomotor activity in the mammalian spinal cord remain poorly understood. These mechanisms supposedly rely on both intrinsic properties of constituting neurons and interactions between them. A subset of Shox2 neurons was suggested to contribute to generation of spinal locomotor activity, but the possible cellular basis for rhythmic bursting in these neurons remains unknown. Ha and Dougherty (2018) recently revealed the presence of bidirectional electrical coupling between Shox2 neurons in neonatal spinal cords, which can be critically involved in neuronal synchronization and generation of populational bursting. Gap junctional connections found between functionally-related Shox2 interneurons decrease with age, possibly being replaced by increasing interactions through chemical synapses. Here, we developed a computational model of a heterogeneous population of neurons sparsely connected by electrical or/and chemical synapses and investigated the dependence of frequency of populational bursting on the type and strength of neuronal interconnections. The model proposes a mechanistic explanation that can account for the emergence of a synchronized rhythmic activity in the neuronal population and provides insights into the possible role of gap junctional coupling between Shox2 neurons in the spinal mechanisms for locomotor rhythm generation.
CD103 Deficiency Promotes Autism (ASD) and Attention-Deficit Hyperactivity Disorder (ADHD) Behavioral Spectra and Reduces Age-Related Cognitive Decline
Authors: Jhun Michelle , Panwar Akanksha , Cordner Ryan , Irvin Dwain K. , Veiga Lucia , Yeager Nicole , Pechnick Robert N. , Schubloom Hanna , Black Keith L. , Wheeler Christopher J.
Published: December 2020

The incidence of autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD), which frequently co-occur, are both rising. The causes of ASD and ADHD remain elusive, even as both appear to involve perturbation of the gut-brain-immune axis. CD103 is an integrin and E-cadherin receptor most prominently expressed on CD8 T cells that reside in gut, brain, and other tissues. CD103 deficiency is well-known to impair gut immunity and resident T cell function, but it's impact on neurodevelopmental disorders has not been examined. We show here that CD8 T cells influence neural progenitor cell function, and that CD103 modulates this impact both directly and potentially by controlling CD8 levels in brain. CD103 knockout (CD103KO) mice exhibited a variety of behavioral abnormalities, including superior cognitive performance coupled with repetitive behavior, aversion to novelty and social impairment in females, with hyperactivity with delayed learning in males. Brain protein markers in female and male CD103KOs coincided with known aspects of ASD and ADHD in humans, respectively. Surprisingly, CD103 deficiency also decreased age-related cognitive decline in both sexes, albeit by distinct means. Together, our findings reveal a novel role for CD103 in brain developmental function, and identify it as a unique factor linking ASD and ADHD etiology. Our data also introduce a new animal model of combined ASD and ADHD with associated cognitive benefits, and reveal potential therapeutic targets for these disorders and age-related cognitive decline.