bluuebunny/crossref_metadata_2025 huggingface dataset:
Electroacupuncture Pretreatment Mitigates Myocardial Ischemia/Reperfusion Injury via XBP1/GRP78/Akt Pathway
Authors: Wang Nisha , Ma Jipeng , Ma Yan , Lu Linhe , Ma Chao , Qin Pei , Gao Erhe , Zuo Mingzhang , Yang Jian , Yang Lifang
Published: June 2021

Myocardial ischemia/reperfusion injury is a common clinical problem and can result in severe cardiac dysfunction. Previous studies have demonstrated the protection of electroacupuncture against myocardial ischemia/reperfusion injury. However, the role of X-box binding protein I (XBP1) signaling pathway in the protection of electroacupuncture was still elusive. Thus, we designed this study and demonstrated that electroacupuncture significantly improved cardiac function during myocardial ischemia/reperfusion injury and reduced cardiac infarct size. Electroacupuncture treatment further inhibited cardiac injury manifested by the decrease of the activities of serum lactate dehydrogenase and creatine kinase-MB. The results also revealed that electroacupuncture elevated the expressions of XBP1, glucose-regulated protein 78 (GRP78), Akt, and Bcl-2 and decreased the Bax and cleaved Caspase 3 expressions. By using the inhibitor of XBP1 in vitro, the results revealed that suppression of XBP1 expression could markedly increase the activities of lactate dehydrogenase and creatine kinase-MB and cell apoptosis, thus exacerbating stimulated ischemia/reperfusion-induced H9c2 cell injury. Compared with stimulated ischemia/reperfusion group, inhibition of XBP1 inhibited the downstream GRP78 and Akt expressions during stimulated ischemia/reperfusion injury. Collectively, our data demonstrated that electroacupuncture treatment activated XBP1/GRP78/Akt signaling to protect hearts from myocardial ischemia/reperfusion injury. These findings revealed the underlying mechanisms of electroacupuncture protection against myocardial ischemia/reperfusion injury and may provide novel therapeutic targets for the clinical treatment of myocardial ischemia/reperfusion injury.
Cardiovascular Magnetic Resonance as Pathophysiologic Tool in Diabetes Mellitus
Authors: Mavrogeni Sophie I. , Bacopoulou Flora , Markousis-Mavrogenis George , Giannakopoulou Aikaterini , Kariki Ourania , Vartela Vasiliki , Kolovou Genovefa , Charmandari Evangelia , Chrousos George
Published: June 2021

Diabetes mellitus can independently contribute to cardiovascular disease and represents a severe risk factor for premature development of cardiovascular disease. A three-fold higher mortality than the general population has been observed in type 1 diabetes mellitus whereas a two- to four-fold increased probability to develop cardiovascular disease has been observed in type 2 diabetes mellitus. Cardiovascular magnetic resonance, a non-radiative modality, is superior to all other modalities in detecting myocardial infarction. The main cardiovascular magnetic resonance sequences used include a) balanced steady-state free precession (bSSFP) for function evaluation; b) T2-W for oedema detection; c) T1 W for ischemia detection during adenosine stress; and d) late gadolinium enhanced T1-W images (LGE), evaluated 15 min after injection of paramagnetic contrast agent gadolinium, which permit the diagnosis of replacement fibrosis, which appears white in the middle of suppressed, nulled myocardium. Although LGE is the technique of choice for diagnosis of replacement fibrosis, it cannot assess diffuse myocardial fibrosis. The application of T1 mapping (native or pre contrast and post contrast) allows identification of diffuse myocardial fibrosis, which is not detectable my other means. Native T1 and Contrast-enhanced T1 mapping are involved in the extracellular volume fraction (ECV) calculation. Recently, 1H-cardiovascular magnetic resonance spectroscopy has been applied to calculate the amount of myocardial triglycerides, but at the moment it is not part of the routine assessment of diabetes mellitus. The multifaceted nature of cardiovascular magnetic resonance has the great potential of concurrent evaluation of function and myocardial ischemia/fibrosis in the same examination and represents an indispensable tool for accurate diagnosis of cardiovascular disease in diabetes mellitus.
Simulation of the HTR-10 Operation History With the PANGU Code
Authors: She Ding , Chen Fubing , Xia Bing , Shi Lei
Published: June 2021

The 10 MW High Temperature Gas-cooled Reactor-Test Module (HTR-10) is the first High Temperature Gas-cooled Reactor (HTGR) in China, which was operated from January 2003 to May 2007. The HTR-10 operation history provides very important data for the validation of HTGR codes. In this paper, the HTR-10 operation history is simulated with the PANGU code, which has been recently developed for HTGR reactor physics analysis and design. Models and parameters are constructed based on the measured data of the actual conditions. The simulation results agree well with the measurements in all steady-state power periods. The discrepancy of keff is generally below 0.5%, and the discrepancy of coolant outlet temperature is generally below 5°C. It is also figured out that the burnup of graphite impurities has considerable influence on the keff at the end of the operation history, which can cause over 1.5% discrepancy when neglecting the burnup of graphite impurities. By this work, the PANGU code’s applicability in actual HTGR fuel cycle simulations is demonstrated.
Abiotic Reduction of Mercury(II) in the Presence of Sulfidic Mineral Suspensions
Authors: Coulibaly Mariame , Mazrui Nashaat M. , Jonsson Sofi , Mason Robert P.
Published: June 2021

Monomethylmercury (CH3Hg) is a neurotoxic pollutant that biomagnifies in aquatic food webs. In sediments, the production of CH3Hg depends on the bacterial activity of mercury (Hg) methylating bacteria and the amount of bioavailable inorganic divalent mercury (HgII). Biotic and abiotic reduction of HgII to elemental mercury (Hg0) may limit the pool of HgII available for methylation in sediments, and thus the amount of CH3Hg produced. Knowledge about the transformation of HgII is therefore primordial to the understanding of the production of toxic and bioaccumulative CH3Hg. Here, we examined the reduction of HgII by sulfidic minerals (FeS(s) and CdS(s)) in the presence of dissolved iron and dissolved organic matter (DOM) using low, environmentally relevant concentrations of Hg and ratio of HgII:FeS(s). Our results show that the reduction of HgII by Mackinawite (FeS(s)) was lower (<15% of the HgII was reduced after 24 h) than when HgII was reacted with DOM or dissolved iron. We did not observe any formation of Hg0 when HgII was reacted with CdS(s) (experiments done under both acidic and basic conditions for up to four days). While reactions in solution were favorable under the experimental conditions, Hg was rapidly removed from solution by co-precipitation. Thermodynamic calculations suggest that in the presence of FeS(s), reduction of the precipitated HgII is surface catalyzed and likely involves S−II as the electron donor. The lack of reaction with CdS may be due to its stronger M-S bond relative to FeS, and the lower concentrations of sulfide in solution. We conclude that the reaction of Hg with FeS(s) proceeds via a different mechanism from that of Hg with DOM or dissolved iron, and that it is not a major environmental pathway for the formation of Hg0 in anoxic environments.
Biological Correlates of Extinction Risk in Resident Philippine Avifauna
Authors: Kittelberger Kyle D. , Neate-Clegg Montague H. C. , Blount J. David , Posa Mary Rose C. , McLaughlin John , Şekercioğlu Çağan Hakkı
Published: June 2021

The majority of the world’s biodiversity occurs in the tropics, but human actions in these regions have precipitated an extinction crisis due to habitat degradation, overexploitation, and climate change. Understanding which ecological, biogeographical, and life-history traits predict extinction risk is critical for conserving species. The Philippines is a hotspot of biodiversity and endemism, but it is a region that also suffers from an extremely high level of deforestation, habitat degradation, and wildlife exploitation. We investigated the biological correlates of extinction risk based on the IUCN Red List threat status among resident Philippine birds using a broad range of ecological, biogeographical, and life history traits previously identified as correlates of extinction risk in birds. We found strong support across competing models for endemism, narrower elevational ranges, high forest dependency, and larger body size as correlates significantly associated with extinction risk. Additionally, we compared observed threat status with threat status fitted by our model, finding fourteen species that are not currently recognized by the IUCN Red List as threatened that may be more threatened than currently believed and therefore warrant heightened conservation focus, and predicted threat statuses for the four Philippine Data Deficient bird species. We also assessed species described in recent taxonomic splits that are recognized by BirdLife International, finding 12 species that have a fitted threat status more severe than their IUCN-designated ones. Our findings provide a framework for avian conservation efforts to identify birds with specific biological correlates that increase a species’ vulnerability to extinction both in the Philippine Archipelago and elsewhere on other tropical islands.
Density Based Distribution Model for Repositioning Strategies of Ride Hailing Services
Authors: Syed Arslan Ali , Dandl Florian , Kaltenhäuser Bernd , Bogenberger Klaus
Published: June 2021

Ride hailing (RH) services have become a common mode of transportation in the last decade. Usually, statistical tools are used to improve their performance, whereby the tools typically divide the whole operational area into multiple regions. These tools usually assume that the regions are independent of each other even though vehicles from one region can be used to serve neighboring regions, thereby a method is required that consistently relates vehicle demand and supply between geographically neighboring regions or to the whole operating area. This hinders tapping into the full potential of region-based performance improvement techniques like the repositioning of idle vehicles. Therefore, we develop an innovative reachability function-based method that coherently builds a relation among all regions in the form of a spatial density of the measured quantity. We use it to calculate the differences of vehicle supply and demand for the whole operational area in the form of an imbalance density. Based on this, we derive a novel repositioning formulation that significantly reduces both the overall vehicle imbalances and the total distance of repositioning trips, and thus improves the long-term RH performance. We test the approach in an agent-based simulation for an RH scenario with automated vehicles, using open-source New York City taxi data as demand. The approach shows a remarkable improvement over the state of the art repositioning strategies that balance the fleet over the individual regions. Furthermore, we introduce kernel-based key performance indicators (KPIs) that can be calculated at the time of making repositioning decisions. We also show the correlation of the KPIs with long-term performance gains. We expect that these KPIs can benefit future statistical (machine learning) approaches for repositioning.
Genome of the Single Human Chromosome 18 as a “Gold Standard” for Its Transcriptome
Authors: Ilgisonis Ekaterina , Vavilov Nikita , Ponomarenko Elena , Lisitsa Andrey , Poverennaya Ekaterina , Zgoda Victor , Radko Sergey , Archakov Alexander
Published: June 2021

The cutoff level applied in sequencing analysis varies according to the sequencing technology, sample type, and study purpose, which can largely affect the coverage and reliability of the data obtained. In this study, we aimed to determine the optimal combination of parameters for reliable RNA transcriptome data analysis. Toward this end, we compared the results obtained from different transcriptome analysis platforms (quantitative polymerase chain reaction, Illumina RNASeq, and Oxford Nanopore Technologies MinION) for the transcriptome encoded by human chromosome 18 (Chr 18) using the same sample types (HepG2 cells and liver tissue). A total of 275 protein-coding genes encoded by Chr 18 was taken as the gene set for evaluation. The combination of Illumina RNASeq and MinION nanopore technologies enabled the detection of at least one transcript for each protein-coding gene encoded by Chr 18. This combination also reduced the probability of false-positive detection of low-copy transcripts due to the simultaneous confirmation of the presence of a transcript by the two fundamentally different technologies: short reads essential for reliable detection (Illumina RNASeq) and long-read sequencing data (MinION). The combination of these technologies achieved complete coverage of all 275 protein-coding genes on Chr 18, identifying transcripts with non-zero expression levels. This approach can improve distinguishing the biological and technical reasons for the absence of mRNA detection for a given gene in transcriptomics.
The RNA-Binding Proteins SRP14 and HMGB3 Control HIV-1 Tat mRNA Processing and Translation During HIV-1 Latency
Authors: Khoury Georges , Lee Michelle Y. , Ramarathinam Sri H. , McMahon James , Purcell Anthony W. , Sonza Secondo , Lewin Sharon R. , Purcell Damian F. J.
Published: June 2021

HIV-1 Tat protein is essential for virus production. RNA-binding proteins that facilitate Tat production may be absent or downregulated in resting CD4+T-cells, the main reservoir of latent HIV in people with HIV (PWH) on antiretroviral therapy (ART). In this study, we examined the role of Tat RNA-binding proteins on the expression of Tat and control of latent and productive infection. Affinity purification coupled with mass spectrometry analysis was used to detect binding partners of MS2-taggedtatmRNA in a T cell-line model of HIV latency. The effect of knockdown and overexpression of the proteins of interest on Tat transactivation and translation was assessed by luciferase-based reporter assays and infections with a dual color HIV reporter virus. Out of the 243 interactions identified, knockdown of SRP14 (Signal Recognition Particle 14) negatively affectedtatmRNA processing and translation as well as Tat-mediated transactivation, which led to an increase in latent infection. On the other hand, knockdown of HMGB3 (High Mobility Group Box 3) resulted in an increase in Tat transactivation and translation as well as an increase in productive infection. Footprinting experiments revealed that SRP14 and HMGB3 proteins bind to TIM-TAM, a conserved RNA sequence-structure intatmRNA that functions as a Tat IRES modulator oftatmRNA. Overexpression of SRP14 in resting CD4+T-cells from patients on ART was sufficient to reverse HIV-1 latency and induce virus production. The role of SRP14 and HMGB3 proteins in controlling HIV Tat expression during latency will be further assessed as potential drug targets.
Vaccine Hesitancy and Rejection of a Vaccine for the Novel Coronavirus in the United States
Authors: Shih Shu-Fang , Wagner Abram L. , Masters Nina B. , Prosser Lisa A. , Lu Yihan , Zikmund-Fisher Brian J.
Published: June 2021

The arrival of the COVID-19 vaccine has been accompanied by increased discussion of vaccine hesitancy. However, it is unclear if there are shared patterns between general vaccine hesitancy and COVID-19 vaccine rejection, or if these are two different concepts. This study characterized rejection of a hypothetical COVID-19 vaccine, and compared patterns of association between general vaccine hesitancy and COVID-19 vaccine rejection. The survey was conducted online March 20-22, 2020. Participants answered questions on vaccine hesitancy and responded if they would accept the vaccine given different safety and effectiveness profiles. We assessed differences in COVID-19 rejection and general vaccine hesitancy through logistic regressions. Among 713 participants, 33.0% were vaccine hesitant, and 18.4% would reject a COVID-19 vaccine. Acceptance varied by effectiveness profile: 10.2% would reject a 95% effective COVID-19 vaccine, but 32.4% would reject a 50% effective vaccine. Those vaccine hesitant were significantly more likely to reject COVID-19 vaccination [odds ratio (OR): 5.56, 95% confidence interval (CI): 3.39, 9.11]. In multivariable logistic regression models, there were similar patterns for vaccine hesitancy and COVID-19 vaccine rejection by gender, race/ethnicity, family income, and political affiliation. But the direction of association flipped by urbanicity (P=0.0146, with rural dwellers less likely to be COVID-19 vaccine rejecters but more likely to be vaccine hesitant in general), and age (P=0.0037, with fewer pronounced differences across age for COVID-19 vaccine rejection, but a gradient of stronger vaccine hesitancy in general among younger ages). During the COVID-19 epidemic’s early phase, patterns of vaccine hesitancy and COVID-19 vaccine rejection were relatively similar. A significant minority would reject a COVID-19 vaccine, especially one with less-than-ideal effectiveness. Preparations for introducing the COVID-19 vaccine should anticipate substantial hesitation and target concerns, especially among younger adults.
sMAdCAM: IL-6 Ratio Influences Disease Progression and Anti-Viral Responses in SARS-CoV-2 Infection
Authors: Jagtap Dhanashree , Bhor Vikrant M. , Bhowmick Shilpa , Kasarpalkar Nandini , Sagvekar Pooja , Kulkarni Bhalchandra , Pathak Manish , Chatterjee Nirjhar , Dolas Pranam , Palav Harsha , Kaginkar Snehal , Bhagat Sharad , Munshi Itti , Parikh Swapneil , Agrawal Sachee , Pawar Chandrakant , Kaneria Mala , Mahale Smita D. , Shastri Jayanthi , Patel Vainav
Published: June 2021

The role of sMAdCAM, an important gut immune migratory marker, remains unexplored in COVID-19 pathogenesis considering recent studies positing the gut as a sanctuary site for SARS-CoV-2 persistence. Thus, assimilating profiles of systemic inflammatory mediators with sMAdCAM levels may provide insights into the progression of COVID-19 disease. Also, the role of these markers in governing virus specific immunity following infection remains largely unexplored. A cohort (n = 84) of SARS-C0V-2 infected individuals included a group of in-patients (n = 60) at various stages of disease progression together with convalescent individuals (n = 24) recruited between April and June 2020 from Mumbai, India. Follow-up of 35 in-patients at day 7 post diagnosis was carried out. Th1/Th2/Th17 cytokines along with soluble MAdCAM (sMAdCAM) levels in plasma were measured. Also, anti-viral humoral response as measured by rapid antibody test (IgG, IgM), Chemiluminescent Immunoassay (IgG), and antibodies binding to SARS-CoV-2 proteins were measured by Surface Plasmon Resonance (SPR) from plasma. IL-6 and sMAdCAM levels among in-patients inversely correlated with one another. When expressed as a novel integrated marker—sMIL index (sMAdCAM/IL-6 ratio)—these levels were incrementally and significantly higher in various disease states with convalescents exhibiting the highest values. Importantly, sMAdCAM levels as well as sMIL index (fold change) correlated with peak association response units of receptor binding domain and fold change in binding to spike respectively as measured by SPR. Our results highlight key systemic and gut homing parameters that need to be monitored and investigated further to optimally guide therapeutic and prophylactic interventions for COVID-19.
Characterization of CD8 T Cell-Mediated Mutations in the Immunodominant Epitope GP33-41 of Lymphocytic Choriomeningitis Virus
Authors: Smyth Mark , Khamina Kseniya , Popa Alexandra , Gudipati Venugopal , Agerer Benedikt , Lercher Alexander , Kosack Lindsay , Endler Lukas , Baazim Hatoon , Viczenczova Csilla , Huppa Johannes B. , Bergthaler Andreas
Published: June 2021

Cytotoxic T lymphocytes (CTLs) represent key immune effectors of the host response against chronic viruses, due to their cytotoxic response to virus-infected cells. In response to this selection pressure, viruses may accumulate escape mutations that evade CTL-mediated control. To study the emergence of CTL escape mutations, we employed the murine chronic infection model of lymphocytic choriomeningitis virus (LCMV). We developed an amplicon-based next-generation sequencing pipeline to detect low frequency mutations in the viral genome and identified non-synonymous mutations in the immunodominant LCMV CTL epitope, GP33-41, in infected wildtype mice. Infected Rag2-deficient mice lacking CTLs did not contain such viral mutations. By using transgenic mice with T cell receptors specific to GP33-41, we characterized the emergence of viral mutations in this epitope under varying selection pressure. We investigated the two most abundant viral mutations by employing reverse genetically engineered viral mutants encoding the respective mutations. These experiments provided evidence that these mutations prevent activation and expansion of epitope-specific CD8 T cells. Our findings on the mutational dynamics of CTL escape mutations in a widely-studied viral infection model contributes to our understanding of how chronic viruses interact with their host and evade the immune response. This may guide the development of future treatments and vaccines against chronic infections.
c-Rel Is Required for IL-33-Dependent Activation of ILC2s
Authors: Zaini Aidil , Fulford Thomas S. , Grumont Raelene J. , Runting Jessica , Rodrigues Grace , Ng Judy , Gerondakis Steve , Zaph Colby , Scheer Sebastian
Published: June 2021

Group 2 innate lymphoid cells (ILC2s) are emerging as important cellular regulators of homeostatic and disease-associated immune processes. The cytokine interleukin-33 (IL-33) promotes ILC2-dependent inflammation and immunity, with IL-33 having been shown to activate NF-κB in a wide variety of cell types. However, it is currently unclear which NF-κB members play an important role in IL-33-dependent ILC2 biology. Here, we identify the NF-κB family member c-Rel as a critical component of the IL-33-dependent activation of ILC2s. Although c-Rel is dispensable for ILC2 development, it is critical for ILC2 function in the lung, with c-Rel-deficient (c-Rel–/–) mice present a significantly reduced response to papain- and IL-33-induced lung inflammation. We also show that the absence of c-Rel reduces the IL-33-dependent expansion of ILC2 precursors and lower levels of IL-5 and IL-13 cytokine production by mature ILC2s in the lung. Together, these results identify the IL-33-c-Rel axis as a central control point of ILC2 activation and function.
Effect of Donor and Recipient ABH-Secretor Status on ABO-Incompatible Living Donor Kidney Transplantation
Authors: Zhang Fan , Yin Saifu , Fan Yu , Song Turun , Huang Zhongli , Liang Jiayu , Wu Jiapei , Yang Youmin , Lin Tao , Wang Xianding
Published: June 2021

Introduction

ABO blood group antigens within grafts are continuously exposed to anti-A/B antibodies in the serum of recipients after ABO-incompatible (ABOi) kidney transplantation and are instrumental in antibody-mediated rejection. Some individuals secrete soluble blood group antigens into body fluids. In this study, we investigated the effect of donor and recipient secretor status on the outcomes of ABOi kidney transplantation.

Methods

Data of a total of 32 patients with ABOi living donor kidney transplantation were retrospectively collected between 2014 and 2020 in West China Hospital. The genotype and phenotype of both donors and recipients were examined and evaluated with post-transplantation anti-A/B titer changes, graft function, and rejection.

Results

Of the 32 recipients and 32 donors, 23 (71.9%) recipients and 27 (84.4%) donors had secretor genotypes, whereas 9 (28.1%) recipients and 5 (15.6%) donors did not. Anti-A/B titers after ABOi kidney transplantation were not significantly influenced by the secretor status of either donors or recipients. The post-transplantation serum creatinine (Scr) levels and estimated glomerular filtration rate (eGFR) was better in weak- or non-secretor recipients at day 30 (Scr P = 0.047, eGFR P = 0.008), day 90 (Scr P = 0.010, eGFR P = 0.005), and month 9 (eGFR P = 0.008), and recipients from secretor donors had a lower incidence of graft rejection in the first year after ABOi transplantation (P = 0.004).

Conclusions

A weak secretor status phenotype was found in both genotypes, i.e., individuals who secreted soluble antigens as well as those who did not. The recipient ABH-secretor status may have an influence on early posttransplant renal function, and the donor ABH-secretor status might affect the incidence of graft rejection.
PD-1 Affects the Immunosuppressive Function of Group 2 Innate Lymphoid Cells in Human Non-Small Cell Lung Cancer
Authors: Shen Chunyi , Liu Chaojun , Zhang Zhen , Ping Yu , Shao Jingwen , Tian Yonggui , Yu Weina , Qin Guohui , Liu Shasha , Wang Liping , Zhang Yi
Published: June 2021

Background

There is increasing evidence that group 2 innate lymphoid cells (ILC2s) play an essential role in allergy and parasitic infection. However, the role of ILC2s in human lung cancer remains unclear.

Methods

ILC2s from peripheral blood mononuclear cells (PBMCs) obtained from healthy donors (HDs) and non-small cell lung cancer (NSCLC) patients, and NSCLC tumor tissues were analyzed via multicolor flow cytometry. ILC2s or CD14+ cells were sorted by fluorescence-activated cell sorting. qPCR and flow cytometry were performed to assess the gene and protein expression of the indicated molecules. M1-like and M2-like macrophages were induced from CD14+ monocytes in vitro.

Results

ILC2s were significantly more enriched in PBMCs and tumor tissues from NSCLC patients than in HDs. After screening for the main immune checkpoint molecules, we found that PD-1 was upregulated in ILC2s in NSCLC patients. Functionally, PD-1high ILC2s from tumor tissues expressed higher levels of IL-4 and IL-13 regarding both mRNA and protein levels than PD-1low ILC2s. Furthermore, PD-1high ILC2s robustly boosted M2-like macrophage polarization in vitro, by secreting IL-4 and IL-13, while neutralization of IL-4 and IL-13 by antibodies abrogated M2-like macrophage polarization.

Conclusion

ILC2s are enriched in NSCLC patients and upregulate PD-1 expression. Upregulation of PD-1 facilitates the immunosuppressive function of ILC2s. PD-1high ILC2s enhance M2-like macrophage polarization by secreting IL-4 and IL-13. PD-1 acts as a positive regulator of the immunosuppressive function of ILC2s in human NSCLC.
Potent SARS-CoV-2-Specific T Cell Immunity and Low Anaphylatoxin Levels Correlate With Mild Disease Progression in COVID-19 Patients
Authors: Lafon Eliott , Diem Gabriel , Witting Christina , Zaderer Viktoria , Bellmann-Weiler Rosa Maria , Reindl Markus , Bauer Angelika , Griesmacher Andrea , Fux Vilmos , Hoermann Gregor , Miller Carl , Zabernigg August , Wöll Ewald , Wilflingseder Doris , Lass-Flörl Cornelia , Posch Wilfried
Published: June 2021

T cells play a fundamental role in the early control and clearance of many viral infections of the respiratory system. In SARS-CoV-2-infected individuals, lymphopenia with drastically reduced CD4+ and CD8+ T cells correlates with Coronavirus disease 2019 (COVID-19)-associated disease severity and mortality. In this study, we characterized cellular and humoral immune responses induced in patients with mild, severe and critical COVID-19. Peripheral blood mononuclear cells of 37 patients with mild, severe and critical COVID-19 and 10 healthy individuals were analyzed by IFNγ ELISpot and multi-color flow cytometry upon stimulation with peptide pools covering complete immunodominant SARS-CoV-2 matrix, nucleocapsid and spike proteins. In addition SARS-CoV-2 antibody levels, neutralization abilities and anaphylatoxin levels were evaluated by various commercially available ELISA platforms. Our data clearly demonstrates a significantly stronger induction of SARS-CoV-2 specific CD8+ T lymphocytes and higher IFNγ production in patients with mild compared to patients with severe or critical COVID-19. In all patients SARS-CoV-2-specific antibodies with similar neutralizing activity were detected, but highest titers of total IgGs were observed in critical patients. Finally, elevated anaphylatoxin C3a and C5a levels were identified in severe and critical COVID-19 patients probably caused by aberrant immune complex formation due to elevated antibody titers in these patients. Crucially, we provide a full picture of cellular and humoral immune responses of COVID-19 patients and prove that robust polyfunctional CD8+ T cell responses concomitant with low anaphylatoxin levels correlate with mild infections. In addition, our data indicates that high SARS-CoV-2 antibody titers are associated with severe disease progression.
Mast Cells Modulate Antigen-Specific CD8+ T Cell Activation During LCMV Infection
Authors: Hackler Yana , Siebenhaar Frank , Löhning Max , Maurer Marcus , Muñoz Melba
Published: June 2021

Mast cells (MCs), strategically localized at mucosal surfaces, provide first-line defense against pathogens and shape innate and adaptive immune responses. Recent studies have shown that MCs are involved in pathogenic responses to several viruses including herpes simplex viruses, dengue virus, vaccinia virus and influenza virus. However, the underlying mechanisms of MCs in the activation of CD8+ T cells during viral infections are not fully understood. Therefore, we investigate the role of MCs in the development of virus-specific CD8+ T cell responses using the well-characterized murine lymphocytic choriomeningitis virus (LCMV) model and the transgenic MasTRECK mice that contain the human diphtheria toxin receptor as an inducible MC-deficient model. Here, we report that MCs are essential for the activation and expansion of virus-specific CD8+ T cells. After MC depletion and subsequent intradermal LCMV infection, the CD8+ T cell effector phenotype and antiviral cytokine production were impaired at the peak of infection (day 8 p.i.). Importantly, MC-deficient mice were unable to control the infection and exhibited significantly higher viral loads in the spleen and in the ear draining lymph nodes compared to that of wild type control mice. In the absence of MCs, dendritic cell (DC) activation was impaired upon LCMV infection. In addition, type-I interferon (IFN) levels in the serum and in the spleen of MC-deficient mice were reduced during the first days of infection. Interestingly, depletion of MCs after intradermal LCMV infection did not impair virus-specific CD8+ T cell expansion, activation or antiviral cytokine production. In summary, our results indicate that MCs play a pivotal role in the activation and antiviral functions of CD8+ T cells through proper DC activation. A better understanding of the impact of MCs on CD8+ T cell responses is mandatory to improve antiviral immune responses.
Lethal and Sublethal Effects of Conventional and Organic Insecticides on the Parasitoid Trissolcus japonicus, a Biological Control Agent for Halyomorpha halys
Authors: Ribeiro Arthur V. , Holle Sarah G. , Hutchison William D. , Koch Robert L.
Published: June 2021

The egg parasitoid Trissolcus japonicus is a natural enemy of Halyomorpha halys, a polyphagous invasive pest in Europe and North and South America. Integration of chemical and biological control tactics could facilitate effective and sustainable integrated pest management programs. This study was conducted to assess (i) the lethal effects of field rates, (ii) the sublethal effects of maximum and half field rates, and (iii) the lethal effects of different routes of exposure of three organic and two conventional insecticides against T. japonicus. Maximum field rates of spinosad and sulfoxaflor resulted in acute lethal toxicity to adult T. japonicus 1 week after residual contact exposure. Maximum and half field rates of pyrethrins, the mixture of azadirachtin and pyrethrins, and clothianidin caused sublethal effects to female wasps through residual contact exposure. Furthermore, all insecticides caused acute lethal effects 1 week after ingestion by unmated female wasps. Taken together, these results suggest that careful planning is necessary to ensure compatibility between biological and chemical control for H. halys. The insecticides evaluated in this study varied in toxicity to T. japonicus and should be used with caution to conserve this natural enemy for biological control of H. halys.
Energetics of Eddy-Mean Flow Interactions in the Amery Ice Shelf Cavity
Authors: Wu Yang , Wang Zhaomin , Liu Chengyan , Yan Liangjun
Published: June 2021

Previous studies demonstrated that eddy processes play an important role in ice shelf basal melting and the water mass properties of ice shelf cavities. However, the eddy energy generation and dissipation mechanisms in ice shelf cavities have not been studied systematically. The dynamic processes of the ocean circulation in the Amery Ice Shelf cavity are studied quantitatively through a Lorenz energy cycle approach for the first time by using the outputs of a high-resolution coupled regional ocean-sea ice-ice shelf model. Over the entire sub-ice-shelf cavity, mean available potential energy (MAPE) is the largest energy reservoir (112 TJ), followed by the mean kinetic energy (MKE, 70 TJ) and eddy available potential energy (EAPE, 10 TJ). The eddy kinetic energy (EKE) is the smallest pool (5.5 TJ), which is roughly 8% of the MKE, indicating significantly suppressed eddy activities by the drag stresses at ice shelf base and bottom topography. The total generation rate of available potential energy is about 1.0 GW, almost all of which is generated by basal melting and seawater refreezing, i.e., the so-called “ice pump.” The energy generated by ice pump is mainly dissipated by the ocean-ice shelf and ocean-bottom drag stresses, amounting to 0.3 GW and 0.2 GW, respectively. The EKE is generated through two pathways: the barotropic pathway MAPE→MKE→EKE (0.03 GW) and the baroclinic pathway MAPE→EAPE→EKE (0.2 GW). In addition to directly supplying the EAPE through baroclinic pathway (0.2 GW), MAPE also provides 0.5 GW of power to MKE to facilitate the barotropic pathway.
Dose-Dependent Effects of Histamine on Growth, Immunity and Intestinal Health in Juvenile Grouper (Epinephelus coioides)
Authors: Liu Zi-Yan , Yang Hong-Ling , Hu Ling-Hao , Yang Wei , Ai Chun-Xiang , Sun Yun-Zhang
Published: June 2021

A 56 day feeding trial was conducted to examine the effects of different levels of dietary histamine on growth performance, immune response, and intestinal health of grouper (Epinephelus coioides). Seven isonitrogenous (46%), isolipidic (10%) diets were prepared with histamine supplement levels of 0 (T0), 0.05% (T1), 0.1% (T2), 0.15% (T3), 0.2% (T4), 0.25% (T5), and 0.3% (T6), respectively. The results showed that histamine supplementation had no significant effects on weight gain rate (WGR), specific growth rate (SGR), feed conversion rate (FCR), hepatosomatic index (HSI), and survival rate (SR) at the initial feeding period (day 0–28), but WGR and SGR had negative linear responses to the dietary histamine level at the whole feeding period (day 0–56), and a significant decrease was observed in groups T5 and T6 compared with T0 (P < 0.05). Supplementation of histamine decreased antioxidant capacity, immune response, the contents of serum interleukin-1 beta (IL-1β), intestinal-type fatty acid-binding protein (FABP2) and intestinal trefoil factor (ITF), and caused serious damage of intestine with significantly decreased VH and MFH of grouper, especially in fish fed with diets supplemented with high doses of histamine (0.25 and 0.3%). The intestinal microbial communities in treatments were different clearly with the control (T0), in terms of beta (β)-diversity boxplots and UPGMA phylogenetic tree based on unweighted unifrac distance. At the phylum level, the relative abundance of Fusobacteria was lower in group T0, while the abundance of Firmicutes was significantly lower in groups T5 and T6 (P < 0.05). At the genus level, the relative abundance of uncultured_bacterium_f_Bacteroidales_S24-7_group, uncultured_bacterium_f_Lachnospiraceae, and Ruminiclostridium were significantly higher in the control, while the abundance of Cetobacterium was significantly higher in groups T5 and T6 (P < 0.05). In conclusion, the present study suggested that up to 0.2% of dietary histamine did not result in a remarkable reduction in growth, immune response, and intestinal health; however, 0.25% or more dietary histamine could cause significant negative effects on growth performance, immune response, and intestinal health in E. coioides.
Local Acidification Limits the Current Production and Biofilm Formation of Shewanella oneidensis MR-1 With Electrospun Anodes
Authors: Erben Johannes , Pinder Zachary A. , Lüdtke Malte S. , Kerzenmacher Sven
Published: June 2021

The anodic current production of Shewanella oneidensis MR-1 is typically lower compared to other electroactive bacteria. The main reason for the low current densities is the poor biofilm growth on most anode materials. We demonstrate that the high current production of Shewanella oneidensis MR-1 with electrospun anodes exhibits a similar threshold current density as dense Geobacter spp biofilms. The threshold current density is a result of local acidification in the biofilm. Increasing buffer concentration from 10 to 40 mM results in a 1.8-fold increase of the current density [(590 ± 25) μA cm−2] while biofilm growth stimulation by riboflavin has little effect on the current production. The current production of a reference material below the threshold did not respond to the increased buffer concentration but could be enhanced by supplemented riboflavin that stimulated the biofilm growth. Our results suggest that the current production with S. oneidensis is limited (1) by the biofilm growth on the anode that can be enhanced by the choice of the electrode material, and (2) by the proton transport through the biofilm and the associated local acidification.
Host Susceptibility Modulates Escovopsis Pathogenic Potential in the Fungiculture of Higher Attine Ants
Authors: Jiménez-Gómez Irina , Barcoto Mariana O. , Montoya Quimi V. , Goes Aryel C. , Monteiro Lana S. V. E. , Bueno Odair C. , Rodrigues Andre
Published: June 2021

Health and disease emerge from intricate interactions between genotypes, phenotypes, and environmental features. The outcomes of such interactions are context-dependent, existing as a dynamic continuum ranging from benefits to damage. In host-microbial interactions, both the host and environmental conditions modulate the pathogenic potential of a microorganism. Microbial interactions are the core of the agricultural systems of ants in the subtribe Attina, which cultivate basidiomycete fungi for food. The fungiculture environment harbors a diverse microbial community, including fungi in the genus Escovopsis that has been studied as damage-causing agent. Here, we consider the ant colony as a host and investigate to what extent its health impacts the dynamics and outcomes of host-Escovopsis interactions. We found that different ant fungal cultivars vary in susceptibility to the same Escovopsis strains in plate-assays interactions. In subcolony-Escovopsis interactions, while healthy subcolonies gradually recover from infection with different concentrations of Escovopsis conidia, insecticide-treated subcolonies evidenced traits of infection and died within 7 days. The opportunistic nature of Escovopsis infections indicates that diseases in attine fungiculture are a consequence of host susceptibility, rather than the effect of a single microbial agent. By addressing the host susceptibility as a major modulator of Escovopsis pathogenesis, our findings expand the understanding of disease dynamics within attine colonies.
Completion of Maize Stripe Virus Genome Sequence and Analysis of Diverse Isolates
Authors: Bolus Stephen , Braithwaite Kathryn S. , Grinstead Samuel C. , Fuentes-Bueno Irazema , Beiriger Robert , Falk Bryce W. , Mollov Dimitre
Published: June 2021

Maize stripe virus is a pathogen of corn and sorghum in subtropical and tropical regions worldwide. We used high-throughput sequencing to obtain the complete nucleotide sequence for the reference genome of maize stripe virus and to sequence the genomes of ten additional isolates collected from the United States or Papua New Guinea. Genetically, maize stripe virus is most closely related to rice stripe virus. We completed and characterized the RNA1 sequence for maize stripe virus, which revealed a large open reading frame encoding a putative protein with ovarian tumor-like cysteine protease, endonuclease, and RNA-dependent RNA polymerase domains. Phylogenetic and amino acid identity analyses among geographically diverse isolates revealed evidence for reassortment in RNA3 that was correlated with the absence of RNA5. This study yielded a complete and updated genetic description of the tenuivirus maize stripe virus and provided insight into potential mechanisms underpinning its diversity.
NADH Fluorescence Lifetime Imaging Microscopy Reveals Selective Mitochondrial Dysfunction in Neurons Overexpressing Alzheimer’s Disease–Related Proteins
Authors: Niederschweiberer Moritz A. , Schaefer Patrick M. , Singh Larry N. , Lausser Ludwig , Bhosale Devyani , Hesse Raphael , Calzia Enrico , Kestler Hans A. , Rueck Angelika , Wallace Douglas C. , von Einem Bjoern , von Arnim Christine A. F.
Published: June 2021

Alzheimer’s disease (AD), the most prevalent form of dementia, affects globally more than 30 million people suffering from cognitive deficits and neuropsychiatric symptoms. Substantial evidence for the involvement of mitochondrial dysfunction in the development and/or progression of AD has been shown in addition to the pathological hallmarks amyloid beta (Aβ) and tau. Still, the selective vulnerability and associated selective mitochondrial dysfunction cannot even be resolved to date. We aimed at optically quantifying mitochondrial function on a single-cell level in primary hippocampal neuron models of AD, unraveling differential involvement of cell and mitochondrial populations in amyloid precursor protein (APP)-associated mitochondrial dysfunction. NADH lifetime imaging is a highly sensitive marker-free method with high spatial resolution. However, deciphering cellular bioenergetics of complex cells like primary neurons has still not succeeded yet. To achieve this, we combined highly sensitive NADH lifetime imaging with respiratory inhibitor treatment, allowing characterization of mitochondrial function down to even the subcellular level in primary neurons. Measuring NADH lifetime of the same neuron before and after respiratory treatment reveals the metabolic delta, which can be taken as a surrogate for cellular redox capacity. Correlating NADH lifetime delta with overexpression strength of Aβ-related proteins on the single-cell level, we could verify the important role of intracellular Aβ-mediated mitochondrial toxicity. Subcellularly, we could demonstrate a higher respiration in neuronal somata in general than dendrites, but a similar impairment of somatic and dendritic mitochondria in our AD models. This illustrates the power of NADH lifetime imaging in revealing mitochondrial function on a single and even subcellular level and its potential to shed light into bioenergetic alterations in neuropsychiatric diseases and beyond.
Motor Sequence Learning Deficits in Idiopathic Parkinson’s Disease Are Associated With Increased Substantia Nigra Activity
Authors: Tzvi Elinor , Bey Richard , Nitschke Matthias , Brüggemann Norbert , Classen Joseph , Münte Thomas F. , Krämer Ulrike M. , Rumpf Jost-Julian
Published: June 2021

Previous studies have shown that persons with Parkinson’s disease (pwPD) share specific deficits in learning new sequential movements, but the neural substrates of this impairment remain unclear. In addition, the degree to which striatal dopaminergic denervation in PD affects the cortico-striato-thalamo-cerebellar motor learning network remains unknown. We aimed to answer these questions using fMRI in 16 pwPD and 16 healthy age-matched control subjects while they performed an implicit motor sequence learning task. While learning was absent in both pwPD and controls assessed with reaction time differences between sequential and random trials, larger error-rates during the latter suggest that at least some of the complex sequence was encoded. Moreover, we found that while healthy controls could improve general task performance indexed by decreased reaction times across both sequence and random blocks, pwPD could not, suggesting disease-specific deficits in learning of stimulus-response associations. Using fMRI, we found that this effect in pwPD was correlated with decreased activity in the hippocampus over time. Importantly, activity in the substantia nigra (SN) and adjacent bilateral midbrain was specifically increased during sequence learning in pwPD compared to healthy controls, and significantly correlated with sequence-specific learning deficits. As increased SN activity was also associated (on trend) with higher doses of dopaminergic medication as well as disease duration, the results suggest that learning deficits in PD are associated with disease progression, indexing an increased drive to recruit dopaminergic neurons in the SN, however, unsuccessfully. Finally, there were no differences between pwPD and controls in task modulation of the cortico-striato-thalamo-cerebellar network. However, a restricted nigral-striatal model showed that negative modulation of SN to putamen connection was larger in pwPD compared to controls during random trials, while no differences between the groups were found during sequence learning. We speculate that learning-specific SN recruitment leads to a relative increase in SN- > putamen connectivity, which returns to a pathological reduced state when no learning takes place.
Improvement of EMG Pattern Recognition Model Performance in Repeated Uses by Combining Feature Selection and Incremental Transfer Learning
Authors: Li Qi , Zhang Anyuan , Li Zhenlan , Wu Yan
Published: June 2021

Electromyography (EMG) pattern recognition is one of the widely used methods to control the rehabilitation robots and prostheses. However, the changes in the distribution of EMG data due to electrodes shifting results in classification decline, which hinders its clinical application in repeated uses. Adaptive learning can solve this problem but takes additional time. To address this, an efficient scheme is developed by comparing the performance of 12 combinations of three feature selection methods [no feature selection (NFS), sequential forward search (SFS), and particle swarm optimization (PSO)] and four classification methods [non-adaptive support vector machine (N-SVM), incremental SVM (I-SVM), SVM based on TrAdaBoost (T-SVM), and I-SVM based on TrAdaBoost (TI-SVM)] in the classification of EMG data of 12 subjects for 5 consecutive days. Our results showed that TI-SVM achieved the highest classification accuracy among the classification methods (p < 0.05). The SFS method achieved the same classification accuracy as that of the scheme trained with the feature vectors selected by the NFS method (p = 0.999) while achieving a lower training time than that of TI-SVM combined with the NFS method (p = 0.043). Although the PSO method outperformed the NFS and SFS methods by achieving reduced training and response times (p < 0.05), the PSO method achieved a considerably lower classification accuracy than that of the scheme trained with the feature vectors selected by the NFS (p = 0.001) or SFS (p = 0.001) method. Furthermore, TI-SVM combined with the SFS method outperformed the CNN method with fine-tuning in classification accuracy on a small data set (p = 0.001). The results indicate that TI-SVM combined with the SFS method is suitable for improving the performance of EMG pattern recognition in repeated uses.