scholarly journals NK cells at the crossroads in COVID-19: a question of timing

2020 ◽  
Vol 7 (3) ◽  
pp. 309-324
Author(s):  
Susana Del Toro-Arreola ◽  
Fabiola Solorzano-Ibarra ◽  
Martha C. Téllez-Bañuelos ◽  
Jesse Haramati
Keyword(s):  
Innate Immunity ◽  
Nk Cells ◽  
Inflammatory Cells ◽  
The Novel ◽  
First Response ◽  
Different Types ◽  
Dependent Cell ◽  
Infected Cells ◽  
Novel Coronavirus

The outbreak of the novel coronavirus SARS-CoV-2 and the attendant physiological symptoms associated with the COVID-19 disease have led to an explosion of interest studying different aspects of the immune response. As of yet, the particular roles of natural killer cells are not well understood in this disease. NK cells are critical first-response cytotoxic cells of the innate immune system. NK cells are traditionally considered important for their roles in innate immunity against tumors and viral infected cells, as well as their ability to produce cytokines, particularly interferon-?, and participate in antibody dependent cell cytotoxicity (ADCC). Here, we describe the role of NK cells in peripheral blood and in the lungs with respect to the pathology caused by SARS-CoV-2 and discuss the implications of proposed different types of therapies on NK cells. Evidence is accumulating that NK cells play an important role in initial surveillance as part of innate immunity. With the progression of the disease and rising inflammation, these cells, when in circulation, appear to become exhausted and ineffective. In the COVID lung, however, a complex interplay between inflammatory cells, chemokines, cytokines and aberrantly activated migratory NK cells occurs, potentiating local inflammation and the critical situation in the lungs.

scholarly journals FACT subunit SUPT16H associates with BRD4 and contributes to silencing of antiviral interferon signaling

2021 ◽  
Author(s):  
Dawei Zhou ◽  
Jun-Gyu Park ◽  
Zhenyu Wu ◽  
Huachao Huang ◽  
Guillaume N Fiches ◽  
...  
Keyword(s):  
Nk Cells ◽  
Viral Infections ◽  
Gene Activation ◽  
The Novel ◽  
Interferon Stimulated Genes ◽  
Middle Domain ◽  
A Subunit ◽  
Infected Cells ◽  
Histone Modification Enzymes

FACT (FAcilitates Chromatin Transcription) is a heterodimeric protein complex composed of SUPT16H and SSRP1, and a histone chaperone participating in chromatin remodeling during gene transcription. FACT complex is profoundly regulated, and contributes to both gene activation and suppression. Here we reported that SUPT16H, a subunit of FACT, is acetylated at lysine 674 (K674) of middle domain (MD), which involves TIP60 histone acetyltransferase. Such acetylation of SUPT16H is recognized by bromodomain protein BRD4, which promotes protein stability of SUPT16H. We further demonstrated that SUPT16H-BRD4 associates with histone modification enzymes (EZH2, HDAC1) and affects histone marks (H3K9me3, H3K27me3 and H3ac). BRD4 is known to profoundly regulate interferon (IFN) signaling, while such function of SUPT16H has never been explored. Surprisingly, our results revealed that SUPT16H genetic knockdown via RNAi or pharmacological inhibition by using its inhibitor, curaxin 137 (CBL0137), results in the induction of IFNs and interferon-stimulated genes (ISGs). Through this mechanism, CBL0137 is shown to efficiently inhibit infection of multiple viruses, including Zika, influenza, and SARS-CoV-2. Furthermore, we demonstrated that CBL0137 also causes the remarkable activation of IFN signaling in natural killer (NK) cells, which promotes the NK-mediated killing of virus-infected cells in a co-culture system using human primary NK cells. Overall, our studies unraveled the previously un-appreciated role of FACT complex in regulating IFN signaling in both epithelial and NK cells, and also proposed the novel application of CBL0137 to treat viral infections.

SARS-COV2 virus and Coronavirus disease (COVID-19)

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 977-982
Author(s):  
Mohamed J. Saadh ◽  
Bashar Haj Rashid M ◽  
Roa’a Matar ◽  
Sajeda Riyad Aldibs ◽  
Hala Sbaih ◽  
...  
Keyword(s):  
Close Contact ◽  
Antiviral Agents ◽  
Health Concern ◽  
The Novel ◽  
Global Public Health ◽  
Fatal Disease ◽  
Mild Disease ◽  
Life Threatening ◽  
Novel Coronavirus

SARS-COV2 virus causes Coronavirus disease (COVID-19) and represents the causative agent of a potentially fatal disease that is of great global public health concern. The novel coronavirus (2019) was discovered in 2019 in Wuhan, the market of the wet animal, China with viral pneumonia cases and is life-threatening. Today, WHO announces COVID-19 outbreak as a pandemic. COVID-19 is likely to be zoonotic. It is transmitted from bats as intermediary animals to human. Also, the virus is transmitted from human to human who is in close contact with others. The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is nearly supportive; the role of antiviral agents is yet to be established. The SARS-COV2 virus spreads faster than its two ancestors, the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. In this article, we aimed to summarize the transmission, symptoms, pathogenesis, diagnosis, treatment, and vaccine to control the spread of this fatal disease.

The role and relationship of mindreading and social attunement in HRI – position statements of interdisciplinary researchers. Workshop HRI'20

2020 ◽  
Author(s):  
Agnieszka Wykowska ◽  
Jairo Pérez-Osorio ◽  
Stefan Kopp
Keyword(s):  
Mental States ◽  
Human Robot Interaction ◽  
Human Interaction ◽  
Artificial Agents ◽  
The Novel ◽  
Robot Interaction ◽  
Novel Coronavirus ◽  
Relationship Of ◽  
The Relationship

This booklet is a collection of the position statements accepted for the HRI’20 conference workshop “Social Cognition for HRI: Exploring the relationship between mindreading and social attunement in human-robot interaction” (Wykowska, Perez-Osorio & Kopp, 2020). Unfortunately, due to the rapid unfolding of the novel coronavirus at the beginning of the present year, the conference and consequently our workshop, were canceled. On the light of these events, we decided to put together the positions statements accepted for the workshop. The contributions collected in these pages highlight the role of attribution of mental states to artificial agents in human-robot interaction, and precisely the quality and presence of social attunement mechanisms that are known to make human interaction smooth, efficient, and robust. These papers also accentuate the importance of the multidisciplinary approach to advance the understanding of the factors and the consequences of social interactions with artificial agents.

scholarly journals CRISPR-Cas System: The Powerful Modulator of Accessory Genomes in Prokaryotes

2021 ◽  
pp. 1-16
Author(s):  
Anca Butiuc-Keul ◽  
Anca Farkas ◽  
Rahela Carpa ◽  
Dumitrana Iordache
Keyword(s):  
Nucleic Acids ◽  
Pathogenic Bacteria ◽  
The Novel ◽  
Defense System ◽  
Guide Rnas ◽  
Crispr Array ◽  
Different Types ◽  
Evolutionary Trajectories ◽  
Novel Coronavirus ◽  
Cas Proteins

Being frequently exposed to foreign nucleic acids, bacteria and archaea have developed an ingenious adaptive defense system, called CRISPR-Cas. The system is composed of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) array, together with CRISPR (<i>cas</i>)-associated genes. This system consists of a complex machinery that integrates fragments of foreign nucleic acids from viruses and mobile genetic elements (MGEs), into CRISPR arrays. The inserted segments (spacers) are transcribed and then used by cas proteins as guide RNAs for recognition and inactivation of the targets. Different types and families of CRISPR-Cas systems consist of distinct adaptation and effector modules with evolutionary trajectories, partially independent. The origin of the effector modules and the mechanism of spacer integration/deletion is far less clear. A review of the most recent data regarding the structure, ecology, and evolution of CRISPR-Cas systems and their role in the modulation of accessory genomes in prokaryotes is proposed in this article. The CRISPR-Cas system&apos;s impact on the physiology and ecology of prokaryotes, modulation of horizontal gene transfer events, is also discussed here. This system gained popularity after it was proposed as a tool for plant and animal embryo editing, in cancer therapy, as antimicrobial against pathogenic bacteria, and even for combating the novel coronavirus – SARS-CoV-2; thus, the newest and promising applications are reviewed as well.

scholarly journals Formulation and Solution of an Inverse Reliability Problem to Simulate the Dynamic Behavior of COVID-19 Pandemic

2021 ◽  
Vol 22 (1) ◽  
pp. 91-107
Author(s):  
F. S. Lobato ◽  
G. M. Platt ◽  
G. B. Libotte ◽  
A. J. Silva Neto
Keyword(s):  
Dynamic Behavior ◽  
Differential Evolution Algorithm ◽  
Iteration Process ◽  
Real Data ◽  
The Novel ◽  
Design Variables ◽  
Different Types ◽  
Evolution Algorithm ◽  
Novel Coronavirus ◽  
Optimization Loop

Different types of mathematical models have been used to predict the dynamic behavior of the novel coronavirus (COVID-19). Many of them involve the formulation and solution of inverse problems. This kind of problem is generally carried out by considering the model, the vector of design variables, and system parameters as deterministic values. In this contribution, a methodology based on a double loop iteration process and devoted to evaluate the influence of uncertainties on inverse problem is evaluated. The inner optimization loop is used to find the solution associated with the highest probability value, and the outer loop is the regular optimization loop used to determine the vector of design variables. For this task, we use an inverse reliability approach and Differential Evolution algorithm. For illustration purposes, the proposed methodology is applied to estimate the parameters of SIRD (Susceptible-Infectious-Recovery-Dead) model associated with dynamic behavior of COVID-19 pandemic considering real data from China's epidemic and uncertainties in the basic reproduction number (R0). The obtained results demonstrate, as expected, that the increase of reliability implies the increase of the objective function value.

scholarly journals Investigation of the genetic variation in ACE2 on the structural recognition by the novel coronavirus (SARS-CoV-2)

2020 ◽  
Author(s):  
Xingyi Guo ◽  
Zhishan Chen ◽  
Yumin Xia ◽  
Weiqiang Lin ◽  
Hongzhi Li
Keyword(s):  
Genetic Variation ◽  
The Novel ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Missense Variants ◽  
Catalytic Metal ◽  
Using Data ◽  
Novel Coronavirus ◽  
Insight Into

Abstract Background: The outbreak of coronavirus disease (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), through its surface spike glycoprotein (S-protein) recognition on the receptor Angiotensin-converting enzyme 2 (ACE2) in humans. However, it remains unclear how genetic variations in ACE2 may affect its function and structure, and consequently alter the recognition by SARS-CoV-2. Methods: We have systemically characterized missense variants in the gene ACE2 using data from the Genome Aggregation Database (gnomAD; N = 141,456). To investigate the putative deleterious role of missense variants, six existing functional prediction tools were applied to evaluate their impact. We further analyzed the structural flexibility of ACE2 and its protein-protein interface with the S-protein of SARS-CoV-2 using our developed Legion Interfaces Analysis (LiAn) program.Results: Here, we characterized a total of 12 ACE2 putative deleterious missense variants. Of those 12 variants, we further showed that p.His378Arg could directly weaken the binding of catalytic metal atom to decrease ACE2 activity and p.Ser19Pro could distort the most important helix to the S-protein. Another seven missense variants may affect secondary structures (i.e. p.Gly211Arg; p.Asp206Gly; p.Arg219Cys; p.Arg219His, p.Lys341Arg, p.Ile468Val, and p.Ser547Cys), whereas p.Ile468Val with AF = 0.01 is only present in Asian.Conclusions: We provide strong evidence of putative deleterious missense variants in ACE2 that are present in specific populations, which could disrupt the function and structure of ACE2. These findings provide novel insight into the genetic variation in ACE2 which may affect the SARS-CoV-2 recognition and infection, and COVID-19 susceptibility and treatment.

scholarly journals FcγRIIIa receptor polymorphism influences NK cell mediated ADCC activity against HIV

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Sneha Pramod Talathi ◽  
Nawaj Najir Shaikh ◽  
Sudhanshu Shekhar Pandey ◽  
Vandana Ashish Saxena ◽  
Megha Sunil Mamulwar ◽  
...  
Keyword(s):  
Cell Activation ◽  
Nk Cell ◽  
Killer Cell ◽  
Adcc Activity ◽  
Efficient Treatment ◽  
Activation Assay ◽  
Dependent Cell ◽  
Infected Cells ◽  
First Time

Abstract Background HIV-specific Antibody Dependent Cell Cytotoxicity (ADCC) has shown to be important in HIV control and resistance. The ADCC is mediated primarily by natural killer cell activated through the binding of FcγRIIIa receptor to the Fc portion of antibody bound to the antigen expressed on the infected cells. However, no data is available on the influence of the polymorphism in FcγRIIIa receptor on HIV-specific ADCC response. Methods The Sanger’s method of sequencing was used to sequence the exon of FcγRIIIa receptor while the ADCC activity was determined using NK cell activation assay. The polymorphism in FcγRIIIa receptor was assessed in HIV-infected Indian individuals with or without HIV-specific ADCC antibodies and its influence on the magnitude of HIV-specific ADCC responses was analyzed. Results Two polymorphisms: V176F (rs396991) and Y158H (rs396716) were observed. The Y158H polymorphism is reported for the first time in Indian population. Both, V176F (V/V genotype) (p = 0.004) and Y158H (Y/H genotype) (p = 0.032) were found to be significantly associated with higher magnitude of HIV-specific ADCC response. Conclusion The study underscores the role of polymorphism in the FcγRIIIa receptor on HIV-specific ADCC response and suggests that the screening of the individuals for FcγRIIIa-V176F and Y158H polymorphisms could be useful for prediction of efficient treatment in monoclonal antibody-based therapies aimed at ADCC in HIV infection.

scholarly journals The Role of Tumor-Associated Macrophages in Leukemia

2019 ◽  
Vol 143 (2) ◽  
pp. 112-117 ◽  
Author(s):  
Yueyang Li ◽  
M. James You ◽  
Yaling Yang ◽  
Dongzhi Hu ◽  
Chen Tian
Keyword(s):  
Stem Cells ◽  
Innate Immunity ◽  
Mesenchymal Stem Cells ◽  
Immune Cells ◽  
Leukemia Cell ◽  
Tumor Associated Macrophages ◽  
Intrinsic Factors ◽  
Different Types ◽  
Tumor Growth And Metastasis

In addition to intrinsic factors, leukemia cell growth is influenced by the surrounding nonhematopoietic cells in the leukemic microenvironment, including fibroblasts, mesenchymal stem cells, vascular cells, and various immune cells. Despite the fact that macrophages are an important component of human innate immunity, tumor-associated macrophages (TAMs) have long been considered as an accomplice promoting tumor growth and metastasis. TAMs are activated by an abnormal malignant microenvironment, polarizing into a specific phenotype and participating in tumor progression. TAMs that exist in the microenvironment of different types of leukemia are called leukemia-associated macrophages (LAMs), which are reported to be associated with the progression of leukemia. This review describes the role of LAMs in different leukemia subtypes.

scholarly journals Arterial Hypertension as a Risk Comorbidity Associated with COVID-19 Pathology

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Alexander Kamyshnyi ◽  
Inna Krynytska ◽  
Victoriya Matskevych ◽  
Mariya Marushchak ◽  
Oleh Lushchak
Keyword(s):  
Arterial Hypertension ◽  
Pressure Control ◽  
The Novel ◽  
Global Public Health ◽  
Angiotensin Converting Enzyme 2 ◽  
Cardiovascular Comorbidities ◽  
Public Health Challenge ◽  
Novel Coronavirus ◽  
Ace2 Gene

Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is an ongoing global public health challenge. Current clinical data suggest that, in COVID-19 patients, arterial hypertension (AH) is one of the most common cardiovascular comorbidities; it can worsen outcomes and increase the risk of admission to intensive care unit (ICU). The exact mechanisms through which AH contributes to the poor prognosis in COVID-19 are not yet clear. The putative relationship between AH and COVID-19 may be linked to the role of angiotensin-converting enzyme 2 (ACE2), a key element of the AH pathophysiology. Another mechanism connecting AH and COVID-19 is the dysregulation of the immune system resulting in a cytokine storm, mediated by an imbalanced response of T helper cells subtypes. Therefore, it is essential to optimize blood pressure control in hypertensive patients and monitor them carefully for cardiovascular and other complications for the duration of COVID-19 infection. The question whether AH-linked ACE2 gene polymorphisms increase the risk and/or worsen the course of SARS-CoV-2 infection should also receive further consideration.

scholarly journals The Role of Dental Professionals in Pandemic Events and Disaster Responses

2020 ◽  
pp. 1-5 ◽  
Author(s):  
Guangwen Li ◽  
Bei Chang ◽  
Hui Li ◽  
Rui Wang ◽  
Gang Li
Keyword(s):  
Human Resources ◽  
Emergency Response ◽  
Mass Casualties ◽  
The Novel ◽  
Public Health Emergencies ◽  
The Past ◽  
Emergency Responses ◽  
Novel Coronavirus ◽  
Dental Professionals

Abstract The past 20 years have seen major public health emergencies and natural disasters, including the Severe Acute Respiratory Syndrome outbreak caused by the SARS-associated coronavirus (SARS-CoV) in 2003; the Wenchuan earthquake in 2008; and the novel coronavirus pandemic (COVID-19) of 2019, which caused mass casualties, infections, and panic. These also resulted in complex demands for medical resources and information, and a shortage of human resources for emergency responses. To address the shortage of human resources required for these emergency responses, Chinese dental professionals made useful contributions. From this work, deficiencies in emergency response training and opportunities for the expansion of rescue capabilities were identified, and relevant recommendations made.

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