scholarly journals The structural role of SARS-CoV-2 genetic background in the emergence and success of spike mutations: the case of the spike A222V mutation

2021 ◽  
Author(s):  
Tiziana Ginex ◽  
Clara Marco-Marín ◽  
Miłosz Wieczór ◽  
Carlos P. Mata ◽  
James M Krieger ◽  
...  
Keyword(s):  
Viral Infection ◽  
Point Mutation ◽  
Genetic Background ◽  
Specific Effect ◽  
Early Summer ◽  
Vaccine Effectiveness ◽  
Computational Studies ◽  
Neutralization Capacity ◽  
The Impact

The S:A222V point mutation, within the G clade, was characteristic of the 20E (EU1) SARS-CoV-2 variant identified in Spain in early summer 2020. This mutation has now reappeared in the Delta subvariant AY.4.2, raising questions about its specific effect on viral infection. We report combined serological, functional, structural and computational studies characterizing the impact of this mutation. Our results reveal that S:A222V promotes an increased RBD opening and slightly increases ACE2 binding as compared to the parent S:D614G clade. Finally, S:A222V does not reduce sera neutralization capacity, suggesting it does not affect vaccine effectiveness.

Role of strain differences on host resistance and the transcriptional response of macrophages to infection withYersinia enterocolitica

2006 ◽  
Vol 25 (1) ◽  
pp. 75-84 ◽  
Author(s):  
Katrin van Erp ◽  
Kristina Dach ◽  
Isabel Koch ◽  
Jürgen Heesemann ◽  
Reinhard Hoffmann
Keyword(s):  
Transcription Factors ◽  
Host Resistance ◽  
Genetic Background ◽  
Antibacterial Properties ◽  
Differentially Expressed ◽  
Transcriptional Responses ◽  
Yersinia Infection ◽  
Ifn Γ ◽  
The Impact

The outcome of a host-pathogen encounter is determined by virulence factors of the pathogen and defense factors of the host. We characterized the impact of host factors [resistant (C57BL/6) or susceptible (BALB/c) genetic background and exposure to interferon (IFN)-γ] on transcriptional responses of bone marrow-derived macrophages (BMDM) to infection with Yersinia enterocolitica. IFN-γ treatment more profoundly altered the transcriptome of BMDM than did bacterial infection or genetic background. In BALB/c BMDM, 1,161 genes were differentially expressed in response to Yersinia infection with or without IFN-γ prestimulation. Fourteen genes (1.2%) could only be induced by BALB/c BMDM in response to Yersinia infection after IFN-γ pretreatment. These genes inhibit apoptosis, activate NF-κB and Erk signaling, are chemotactic to neutrophils, and are involved in cytoskeletal reorganization, hence possibly in phagocytosis. Ten of these genes possess a common module of binding sites for Hox, Pou, and Creb transcription factors in 2 kb of upstream genomic sequence, suggesting a possible novel role of these transcription factors in regulation of immune responses. Fifty-two of one thousand fifty differentially expressed genes (4.9%) were induced more strongly by C57BL/6 BMDM in response to Yersinia infection than BALB/c BMDM. These genes activate NK cells, have antibacterial properties, or are involved in sensing chemokines and lipopolysaccharide (LPS). These data show that host resistance factors modulate a surprisingly small, but identifiable and functionally significant, portion of the macrophage transcriptome in response to Yersinia infection.

scholarly journals AMBRA1 promotes apoptosis induced by dsRNA and virus through interacting with and stabilizing MAVS

2021 ◽  
Author(s):  
Yuxia Lin ◽  
Changbai Huang ◽  
Huixin Gao ◽  
Xiaobo Li ◽  
Quanshi Lin ◽  
...  
Keyword(s):  
Viral Infection ◽  
Cellular Response ◽  
Semliki Forest Virus ◽  
Mitochondrial Localization ◽  
Apoptosis Pathway ◽  
Mitochondrial Antiviral Signaling ◽  
Induced Apoptosis ◽  
The Impact ◽  
Mitochondrial Antiviral Signaling Protein

Apoptosis is an important cellular response to viral infection. In current study, we identified activating molecule in Beclin1-regulated autophagy protein 1 (AMBRA1) as a positive regulator of apoptosis triggered by dsRNA. Depletion of AMBRA1 by gene editing significantly reduced dsRNA-induced apoptosis, which was largely restored by trans-complementation of AMBRA1. Mechanistically, AMBRA1 interacts with mitochondrial antiviral-signaling protein (MAVS), a key mitochondrial adaptor in the apoptosis pathway induced by dsRNA and viral infection. Further Co-IP analysis demonstrated that the mitochondrial localization of MAVS was essential for their interaction. The impact of AMBRA1 on dsRNA-induced apoptosis relied on the presence of MAVS and caspase-8. AMBRA1 was involved in the stabilization of MAVS through preventing its proteasomal degradation induced by dsRNA. Consistently, AMBRA1 upregulated the apoptosis induced by Semliki Forest virus infection. Taken together, our work illustrated a role of AMBRA1 in the virus-induced apoptosis through interacting with and stabilizing MAVS.

scholarly journals Role of ACE2 in pregnancy and potential implications for COVID-19 susceptibility

2021 ◽  
Vol 135 (15) ◽  
pp. 1805-1824
Author(s):  
Nayara Azinheira Nobrega Cruz ◽  
Danielle Stoll ◽  
Dulce Elena Casarini ◽  
Mariane Bertagnolli
Keyword(s):  
Viral Infection ◽  
Viral Entry ◽  
Renin Angiotensin System ◽  
Current Evidence ◽  
Maternal Circulation ◽  
Disease Manifestation ◽  
Kinin System ◽  
Kallikrein Kinin System ◽  
The Impact

Abstract In times of coronavirus disease 2019 (COVID-19), the impact of severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 infection on pregnancy is still unclear. The presence of angiotensin-converting enzyme (ACE) 2 (ACE2), the main receptor for SARS-CoV-2, in human placentas indicates that this organ can be vulnerable for viral infection during pregnancy. However, for this to happen, additional molecular processes are critical to allow viral entry in cells, its replication and disease manifestation, particularly in the placenta and/or feto–maternal circulation. Beyond the risk of vertical transmission, COVID-19 is also proposed to deplete ACE2 protein and its biological actions in the placenta. It is postulated that such effects may impair essential processes during placentation and maternal hemodynamic adaptations in COVID-19 pregnancy, features also observed in several disorders of pregnancy. This review gathers information indicating risks and protective features related to ACE2 changes in COVID-19 pregnancies. First, we describe the mechanisms of SARS-CoV-2 infection having ACE2 as a main entry door and current evidence of viral infection in the placenta. Further, we discuss the central role of ACE2 in physiological systems such as the renin–angiotensin system (RAS) and the kallikrein–kinin system (KKS), both active during placentation and hemodynamic adaptations of pregnancy. Significant knowledge gaps are also identified and should be urgently filled to better understand the fate of ACE2 in COVID-19 pregnancies and the potential associated risks. Emerging knowledge will be able to improve the early stratification of high-risk pregnancies with COVID-19 exposure as well as to guide better management and follow-up of these mothers and their children.

scholarly journals Role of genetic polymorphism in the development of sepsis in infants

2015 ◽  
Vol 17 (2) ◽  
pp. 59
Author(s):  
S. A. Sergeev ◽  
O. V. Strunin ◽  
Ye. Ye. Litasova
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Genetic Background ◽  
Individual Response ◽  
Inflammatory Reactions ◽  
Systemic Inflammatory Reaction ◽  
Genes Encoding ◽  
The Difference ◽  
The Impact

Sepsis and its consequences continue to be a major cause of morbidity and mortality in the intensive care unit (ICU). The evidence that endogenous mediators actually mediate an individual response to the infection has led to the development of different approaches to assess the impact of each person on the course of the disease. The role of the genetic background and the susceptibility to human inflammatory response amplitude are determined by the variability of the genes encoding endogenous mediators which are produced during inflammation. Pro-and anti-inflammatory reactions influence the susceptibility and the outcomes in patients with sepsis and systemic inflammation. Thus, all genes encoding proteins involved in the transduction of inflammatory genes are candidates for detection of a human's genetic background responsible for the difference in interpersonal systemic inflammatory reaction.

The effect of loneliness on cancer mortality.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10070-10070
Author(s):  
Simona D'ippolito ◽  
Ettore Ambrosini ◽  
Malihe Shams ◽  
Giuseppe Calì ◽  
Davide Pastorelli
Keyword(s):  
Cancer Mortality ◽  
Specific Effect ◽  
Health Concern ◽  
Cancer Type ◽  
Course Of Disease ◽  
Clinical Variables ◽  
Important Health ◽  
Interaction Anxiety ◽  
The Impact

10070 Background: Convergent findings indicate the need of broadening the vision of cancer beyond known prognostic factors, as many variables of different nature equally affect the course of disease. Loneliness has been found to be associated with various health outcomes, but its relationship with cancer remains unclear. Here we aimed to investigate the specific effect of loneliness and other demographic, psychological, and clinical variables on cancer mortality and to validate the Italian UCLA Loneliness Scale in cancer patients. Methods: This descriptive and correlational study was conducted at the Veneto Institute of Oncology in Padua. 400 patients undergoing chemotherapy from 01/2014 to 06/2015 were enrolled. The sample was stratified by sex and age (4 groups, 40-80 y). We collected demographic, clinical (site and stage of cancer, type of chemotherapy, death date), and psychosocial [self-esteem (RSE), perceived social support (MSPSS), social interaction anxiety (SIAS), personality (EPQR), and depression (BDI)] data. Results: GLM analyses: loneliness was higher in women than men (F(1,398) = 7.5, p = .006) and it linearly increased with age (F(1,398) = 10.9, p = .001). Loneliness was also influenced by marital status (F(3,396) = 2.9, p = .037), cohabitant offspring (F(1,398) = 7, p = .008), and educational level (F(3,396) = 4.7, p = .003), but not by clinical variables (all ps > .05). Correlation analyses: loneliness was inversely related to RSE (r = -.51), MSPSS (r = -.52), and extroversion (r = -.32), and directly related to SIAS (r = .46), neuroticism (r = .43), and BDI (r = .44). More importantly, a hierarchical binomial logistic regression revealed that patients’ mortality was reliably predicted by gender, stage of cancer at diagnosis, time from diagnosis to UCLA collection, BDI, and UCLA (HL χ2(8) = 3.53, p = .90). In particular, high BDI predicted higher mortality (Wald = 11.6, p < .001); surprisingly, after controlling for BDI and other effects, high loneliness predicted lower mortality (Wald = 7, p = .008). Conclusions: Our results replicate prior research and reveal a surprising association between loneliness and mortality risk after partialling out the impact of, especially, depression. This suggests the role of loneliness on cancer course as an important health concern.

In terms of radiative forcing, not all BC emissions are equal

2021 ◽  
Author(s):  
Petri Räisänen ◽  
Antti-Ilari Partanen ◽  
Risto Makkonen ◽  
Joonas Merikanto ◽  
Mikko Savolahti ◽  
...  
Keyword(s):  
Radiative Forcing ◽  
Large Scale ◽  
Climate Model ◽  
Early Summer ◽  
Subarctic Region ◽  
Emission Changes ◽  
Aerosol Emissions ◽  
The Impact ◽  
Atmospheric Concentrations

&lt;p&gt;The development of robust emission metrics to guide climate policy is more complicated for short-lived climate forcers like black carbon (BC) than for long-lived greenhouse gases like CO&lt;sub&gt;2&lt;/sub&gt;. The challenge is that for short-lived climate forcers, the atmospheric concentrations, the radiative forcing (RF), and ultimately, effects on climate, depend on the location and timing of the emissions. &amp;#160;In the present work, the impact of emission location and season on the RF resulting from emissions of BC is studied using the NorESM1 climate model. NorESM1 is run in a configuration in which the distribution of aerosols is simulated using a state-of-the-art aerosol scheme, but the interactive aerosols are not allowed to influence the simulated meteorological conditions. Consequently, the patterns of weather are repeated identically irrespective of the assumed aerosol emissions. This allows for an essentially noise-free evaluation of the radiative forcing associated with changes in aerosol emissions, irrespective of the magnitude and spatiotemporal extent of the emission changes.&lt;/p&gt;&lt;p&gt;We employ the model to systematically evaluate the radiative forcing efficiency (i.e., global-mean RF divided by the emissions) of BC emissions, for various assumptions about the latitude, longitude and season of the emissions. The BC direct effect and the effect of BC on snow albedo are considered. Preliminary results from tests focusing on BC emissions in the subarctic region (60-70&amp;#176;N) indicate the RF efficiency depends strongly both on the timing and longitude of the emissions. The RF efficiency of emissions in spring and summer is much larger than that of emissions in fall and winter, mainly due to the stronger insolation. Furthermore, emissions in the Siberian and North American sectors have higher RF efficiency than emissions in the Atlantic and European sectors. This is largely because emissions from subarctic Siberia and North America preferentially increase the atmospheric BC burden and BC deposition in regions with seasonal snow cover persisting into late spring / early summer. This acts to increase both the BC direct RF and the RF due to BC in snow. Furthermore, long atmospheric residence times act to increase the direct RF associated with Siberian BC emissions in summer.&lt;/p&gt;&lt;p&gt;An implication is that the use of large-scale mean (e.g., subarctic average) emission metrics may mispresent the role of BC emissions from smaller regions like individual countries.&lt;/p&gt;

scholarly journals Differences between Cerebral Organoids Derived from a non-PD and a Parkinson’s Patient: A Potential Vulnerability for Neuroinvasive Viruses

2021 ◽  
Author(s):  
Emily Schultz ◽  
Tyanthony Jones ◽  
Sibei Xu ◽  
Dana Dean ◽  
Bernd Zechmann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Innate Immunity ◽  
Neurodegenerative Diseases ◽  
Viral Infection ◽  
Genetic Background ◽  
Neurological Diseases ◽  
Muscarinic Acetylcholine Receptors ◽  
Cns Infection ◽  
Significant Difference ◽  
The Impact

The development of 3D cerebral brain organoids which accurately resemble aspects of the human brain permits a more accurate characterization of physiological processes and neurological diseases. Cerebral organoids can be grown from stem cell lines with various genetic backgrounds allowing multiple neurodegenerative diseases to be modeled. While dysfunction in neurotransmission of patients with neurodegenerative diseases is expected, the impact of chronic neurodegeneration on the response to viral infection of the CNS is poorly understood. For instance, several mosquito-borne viruses like Dengue virus and West Nile Virus cause post-viral parkinsonism. How CNS infection might impact a host with inherent CNS dysfunction such as Parkinson&rsquo;s Disease in poorly understood. This preliminary, observational study aimed to understand dysfunction in intrinsic and innate expression of a patient with a neurodegenerative disease and a non-affected individual in relation to potential viral infection in the CNS. Cerebral organoids were generated from human induced pluripotent stem cells with a normal genetic background or with idiopathic Parkinson&rsquo;s Disease. After differentiation and maturation, organoid size, gene expression and immunofluorescence were evaluated to assess neurotransmission and innate immunity. While there was no significant difference in size of the organoids with a normal or Parkinson&rsquo;s genetic background, gene expression studies identified multiple differences in innate immunity and neurotransmission. Immunofluorescence also identified differences in protein expression related to neurotransmission and innate immunity. Of note, organoids derived from a Parkinson&rsquo;s patient exhibited endogenous up-regulation of dopamine and muscarinic acetylcholine receptors, GABA, glycine, and glutamate targets, and the majority of cytokines. This expression pattern suggests a chronic state of neuroexcitation and neuroinflammation in this population of organoids.

Intergroup Threat and Outgroup Attitudes

2013 ◽  
Vol 44 (5) ◽  
pp. 311-319 ◽  
Author(s):  
Marco Brambilla ◽  
David A. Butz
Keyword(s):  
Gay Men ◽  
Social Group ◽  
Welfare Recipients ◽  
Intergroup Attitudes ◽  
Social Policies ◽  
Intergroup Threat ◽  
Economic Threat ◽  
The Impact ◽  
General Climate

Two studies examined the impact of macrolevel symbolic threat on intergroup attitudes. In Study 1 (N = 71), participants exposed to a macrosymbolic threat (vs. nonsymbolic threat and neutral topic) reported less support toward social policies concerning gay men, an outgroup whose stereotypes implies a threat to values, but not toward welfare recipients, a social group whose stereotypes do not imply a threat to values. Study 2 (N = 78) showed that, whereas macrolevel symbolic threat led to less favorable attitudes toward gay men, macroeconomic threat led to less favorable attitudes toward Asians, an outgroup whose stereotypes imply an economic threat. These findings are discussed in terms of their implications for understanding the role of a general climate of threat in shaping intergroup attitudes.

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