scholarly journals Functional Landscape of SARS-CoV-2 Cellular Restriction

Author(s):  
Laura Martin-Sancho ◽  
Mary K. Lewinski ◽  
Lars Pache ◽  
Charlotte A. Stoneham ◽  
Xin Yin ◽  
...  

SUMMARYA deficient interferon response to SARS-CoV-2 infection has been implicated as a determinant of severe COVID-19. To identify the molecular effectors that govern interferon control of SARS-CoV-2 infection, we conducted a large-scale gain-of-function analysis that evaluated the impact of human interferon stimulated genes (ISGs) on viral replication. A limited subset of ISGs were found to control viral infection, including endosomal factors that inhibited viral entry, nucleic acid binding proteins that suppressed viral RNA synthesis, and a highly enriched cluster of ER and Golgi-resident ISGs that inhibited viral translation and egress. These included the type II integral membrane protein BST2/tetherin, which was found to impede viral release, and is targeted for immune evasion by SARS-CoV-2 Orf7a protein. Overall, these data define the molecular basis of early innate immune control of viral infection, which will facilitate the understanding of host determinants that impact disease severity and offer potential therapeutic strategies for COVID-19.

2021 ◽  
Vol 135 (15) ◽  
pp. 1805-1824
Author(s):  
Nayara Azinheira Nobrega Cruz ◽  
Danielle Stoll ◽  
Dulce Elena Casarini ◽  
Mariane Bertagnolli

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.


2020 ◽  
Author(s):  
Zhan Qi ◽  
Christophe Jung ◽  
Peter Bandilla ◽  
Claudia Ludwig ◽  
Mark Heron ◽  
...  

SUMMARYThe core promoter, the region immediately surrounding the transcription start site, plays a central role in setting metazoan gene expression levels, but how exactly it ‘computes’ expression remains poorly understood. To dissect core promoter function, we carried out a comprehensive structure-function analysis to measure synthetic promoters’ activities, with and without an external stimulus (hormonal activation). By using robotics and a dual-luciferase reporter assay, we tested ∼3000 mutational variants representing 19 different Drosophila melanogaster promoter architectures. We explored the impact of different types of mutations, including knockout of individual sequence motifs and motif combinations, variations of motif strength, positioning, and flanking sequences. We observe strong effects of the mutations on activity, and a linear combination of the individual motif features can largely account for the combinatorial effects on core promoter activity. Our findings shed new light on the quantitative assessment of gene expression, a fundamental process in all metazoans.


2021 ◽  
Author(s):  
Flora Vincent ◽  
Matti Gralka ◽  
Guy Schleyer ◽  
Daniella J Schatz ◽  
Miguel Cabrera-Brudau ◽  
...  

Algal blooms are hotspots of marine primary production and play central roles in microbial ecology and global nutrient cycling. When blooms collapse, organic carbon is transferred to higher trophic levels, microbial respiration or sinking in proportions that depend on the dominant mortality agent. Viral infection can lead to bloom termination, but its impact on the fate of carbon remains an open question. Here, we characterized the consequences of viral infection on the microbiome composition and biogeochemical landscape of marine ecosystems by conducting a large-scale mesocosm experiment. Moniroting of seven induced coccolithophore blooms, which showed different degrees of viral infection, revealed that only high levels of viral infection caused significant shifts in the composition of free-living bacterial and eukaryotic assemblages. Intriguingly, viral infection favored the growth of eukaryotic heterotrophs (thraustochytrids) over bacteria as potential recyclers of organic matter. By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection can increase per-cell rates of extracellular carbon release by 2-4.5 fold. This happened via production of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. These results reveal the impact of viral infection on the fate of carbon through microbial recyclers of organic matter in large-scale coccolithophore blooms.


2021 ◽  
Author(s):  
Flora VINCENT ◽  
Matti Gralka ◽  
Guy Schleyer ◽  
Daniella Schatz ◽  
Miguel Cabrera-Brufau ◽  
...  

Abstract Algal blooms are hotspots of marine primary production and play central roles in microbial ecology and global nutrient cycling. When blooms collapse, organic carbon is transferred to higher trophic levels, microbial respiration or sinking in proportions that depend on the dominant mortality agent. Viral infection can lead to bloom termination, but its impact on the fate of carbon remains an open question. Here, we characterized the consequences of viral infection on the microbiome composition and biogeochemical landscape of marine ecosystems by conducting a large-scale mesocosm experiment. Moniroting of seven induced coccolithophore blooms, which showed different degrees of viral infection, revealed that only high levels of viral infection caused significant shifts in the composition of free-living bacterial and eukaryotic assemblages. Intriguingly, viral infection favored the growth of eukaryotic heterotrophs (thraustochytrids) over bacteria as potential recyclers of organic matter. By combining modeling and quantification of active viral infection at a single-cell resolution, we estimate that viral infection can increase per-cell rates of extracellular carbon release by 2-4.5 fold. This happened via production of acidic polysaccharides and particulate inorganic carbon, two major contributors to carbon sinking into the deep ocean. These results reveal the impact of viral infection on the fate of carbon through microbial recyclers of organic matter in large-scale coccolithophore blooms.


2020 ◽  
Vol 59 (04) ◽  
pp. 294-299 ◽  
Author(s):  
Lutz S. Freudenberg ◽  
Ulf Dittmer ◽  
Ken Herrmann

Abstract Introduction Preparations of health systems to accommodate large number of severely ill COVID-19 patients in March/April 2020 has a significant impact on nuclear medicine departments. Materials and Methods A web-based questionnaire was designed to differentiate the impact of the pandemic on inpatient and outpatient nuclear medicine operations and on public versus private health systems, respectively. Questions were addressing the following issues: impact on nuclear medicine diagnostics and therapy, use of recommendations, personal protective equipment, and organizational adaptations. The survey was available for 6 days and closed on April 20, 2020. Results 113 complete responses were recorded. Nearly all participants (97 %) report a decline of nuclear medicine diagnostic procedures. The mean reduction in the last three weeks for PET/CT, scintigraphies of bone, myocardium, lung thyroid, sentinel lymph-node are –14.4 %, –47.2 %, –47.5 %, –40.7 %, –58.4 %, and –25.2 % respectively. Furthermore, 76 % of the participants report a reduction in therapies especially for benign thyroid disease (-41.8 %) and radiosynoviorthesis (–53.8 %) while tumor therapies remained mainly stable. 48 % of the participants report a shortage of personal protective equipment. Conclusions Nuclear medicine services are notably reduced 3 weeks after the SARS-CoV-2 pandemic reached Germany, Austria and Switzerland on a large scale. We must be aware that the current crisis will also have a significant economic impact on the healthcare system. As the survey cannot adapt to daily dynamic changes in priorities, it serves as a first snapshot requiring follow-up studies and comparisons with other countries and regions.


2020 ◽  
Vol 6 (5) ◽  
pp. 1183-1189
Author(s):  
Dr. Tridibesh Tripathy ◽  
Dr. Umakant Prusty ◽  
Dr. Chintamani Nayak ◽  
Dr. Rakesh Dwivedi ◽  
Dr. Mohini Gautam

The current article of Uttar Pradesh (UP) is about the ASHAs who are the daughters-in-law of a family that resides in the same community that they serve as the grassroots health worker since 2005 when the NRHM was introduced in the Empowered Action Group (EAG) states. UP is one such Empowered Action Group (EAG) state. The current study explores the actual responses of Recently Delivered Women (RDW) on their visits during the first month of their recent delivery. From the catchment area of each of the 250 ASHAs, two RDWs were selected who had a child in the age group of 3 to 6 months during the survey. The response profiles of the RDWs on the post- delivery first month visits are dwelled upon to evolve a picture representing the entire state of UP. The relevance of the study assumes significance as detailed data on the modalities of postnatal visits are available but not exclusively for the first month period of their recent delivery. The details of the post-delivery first month period related visits are not available even in large scale surveys like National Family Health Survey 4 done in 2015-16. The current study gives an insight in to these visits with a five-point approach i.e. type of personnel doing the visit, frequency of the visits, visits done in a particular week from among those four weeks separately for the three visits separately. The current study is basically regarding the summary of this Penta approach for the post- delivery one-month period.     The first month period after each delivery deals with 70% of the time of the postnatal period & the entire neonatal period. Therefore, it does impact the Maternal Mortality Rate & Ratio (MMR) & the Neonatal Mortality Rates (NMR) in India and especially in UP through the unsafe Maternal & Neonatal practices in the first month period after delivery. The current MM Rate of UP is 20.1 & MM Ratio is 216 whereas the MM ratio is 122 in India (SRS, 2019). The Sample Registration System (SRS) report also mentions that the Life Time Risk (LTR) of a woman in pregnancy is 0.7% which is the highest in the nation (SRS, 2019). This means it is very risky to give birth in UP in comparison to other regions in the country (SRS, 2019). This risk is at the peak in the first month period after each delivery. Similarly, the current NMR in India is 23 per 1000 livebirths (UNIGME,2018). As NMR data is not available separately for states, the national level data also hold good for the states and that’s how for the state of UP as well. These mortalities are the impact indicators and such indicators can be reduced through long drawn processes that includes effective and timely visits to RDWs especially in the first month period after delivery. This would help in making their post-natal & neonatal stage safe. This is the area of post-delivery first month visit profile detailing that the current article helps in popping out in relation to the recent delivery of the respondents.   A total of four districts of Uttar Pradesh were selected purposively for the study and the data collection was conducted in the villages of the respective districts with the help of a pre-tested structured interview schedule with both close-ended and open-ended questions.  The current article deals with five close ended questions with options, two for the type of personnel & frequency while the other three are for each of the three visits in the first month after the recent delivery of respondents. In addition, in-depth interviews were also conducted amongst the RDWs and a total 500 respondents had participated in the study.   Among the districts related to this article, the results showed that ASHA was the type of personnel who did the majority of visits in all the four districts. On the other hand, 25-40% of RDWs in all the 4 districts replied that they did not receive any visit within the first month of their recent delivery. Regarding frequency, most of the RDWs in all the 4 districts received 1-2 times visits by ASHAs.   Regarding the first visit, it was found that the ASHAs of Barabanki and Gonda visited less percentage of RDWs in the first week after delivery. Similarly, the second visit revealed that about 1.2% RDWs in Banda district could not recall about the visit. Further on the second visit, the RDWs responded that most of them in 3 districts except Gonda district did receive the second postnatal visit in 7-15 days after their recent delivery. Less than half of RDWs in Barabanki district & just more than half of RDWs in Gonda district received the third visit in 15-21 days period after delivery. For the same period, the majority of RDWs in the rest two districts responded that they had been entertained through a home visit.


e-Finanse ◽  
2018 ◽  
Vol 14 (4) ◽  
pp. 67-76
Author(s):  
Piotr Bartkiewicz

AbstractThe article presents the results of the review of the empirical literature regarding the impact of quantitative easing (QE) on emerging markets (EMs). The subject is of interest to policymakers and researchers due to the increasingly larger role of EMs in the world economy and the large-scale capital flows occurring after 2009. The review is conducted in a systematic manner and takes into consideration different methodological choices, samples and measurement issues. The paper puts the summarized results in the context of transmission channels identified in the literature. There are few distinct methodological approaches present in the literature. While there is a consensus regarding the direction of the impact of QE on EMs, its size and durability have not yet been assessed with sufficient precision. In addition, there are clear gaps in the empirical findings, not least related to relative underrepresentation of the CEE region (in particular, Poland).


2019 ◽  
Vol 20 (2) ◽  
pp. 123-129 ◽  
Author(s):  
Mariana Jesus ◽  
Tânia Silva ◽  
César Cagigal ◽  
Vera Martins ◽  
Carla Silva

Introduction: The field of nutritional psychiatry is a fast-growing one. Although initially, it focused on the effects of vitamins and micronutrients in mental health, in the last decade, its focus also extended to the dietary patterns. The possibility of a dietary cost-effective intervention in the most common mental disorder, depression, cannot be overlooked due to its potential large-scale impact. Method: A classic review of the literature was conducted, and studies published between 2010 and 2018 focusing on the impact of dietary patterns in depression and depressive symptoms were included. Results: We found 10 studies that matched our criteria. Most studies showed an inverse association between healthy dietary patterns, rich in fruits, vegetables, lean meats, nuts and whole grains, and with low intake of processed and sugary foods, and depression and depressive symptoms throughout an array of age groups, although some authors reported statistical significance only in women. While most studies were of cross-sectional design, making it difficult to infer causality, a randomized controlled trial presented similar results. Discussion: he association between dietary patterns and depression is now well-established, although the exact etiological pathways are still unknown. Dietary intervention, with the implementation of healthier dietary patterns, closer to the traditional ones, can play an important role in the prevention and adjunctive therapy of depression and depressive symptoms. Conclusion: More large-scale randomized clinical trials need to be conducted, in order to confirm the association between high-quality dietary patterns and lower risk of depression and depressive symptoms.


Sign in / Sign up

Export Citation Format

Share Document