scholarly journals A Transcription Regulatory Sequence in the 5′ Untranslated Region of SARS-CoV-2 Is Vital for Virus Replication with an Altered Evolutionary Pattern against Human Inhibitory MicroRNAs

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 319
Author(s):  
Manijeh Mohammadi-Dehcheshmeh ◽  
Sadrollah Molaei Moghbeli ◽  
Samira Rahimirad ◽  
Ibrahim O. Alanazi ◽  
Zafer Saad Al Shehri ◽  
...  
Keyword(s):  
Binding Energy ◽  
Virus Replication ◽  
Lung Biopsy ◽  
Untranslated Region ◽  
Meta Analysis ◽  
A549 Cells ◽  
Leader Sequence ◽  
Regulatory Sequence ◽  
Evolutionary Pattern

Our knowledge of the evolution and the role of untranslated region (UTR) in SARS-CoV-2 pathogenicity is very limited. Leader sequence, originated from UTR, is found at the 5′ ends of all encoded SARS-CoV-2 transcripts, highlighting its importance. Here, evolution of leader sequence was compared between human pathogenic and non-pathogenic coronaviruses. Then, profiling of microRNAs that can inactivate the key UTR regions of coronaviruses was carried out. A distinguished pattern of evolution in leader sequence of SARS-CoV-2 was found. Mining all available microRNA families against leader sequences of coronaviruses resulted in discovery of 39 microRNAs with a stable thermodynamic binding energy. Notably, SARS-CoV-2 had a lower binding stability against microRNAs. hsa-MIR-5004-3p was the only human microRNA able to target the leader sequence of SARS and to a lesser extent, also SARS-CoV-2. However, its binding stability decreased remarkably in SARS-COV-2. We found some plant microRNAs with low and stable binding energy against SARS-COV-2. Meta-analysis documented a significant (p < 0.01) decline in the expression of MIR-5004-3p after SARS-COV-2 infection in trachea, lung biopsy, and bronchial organoids as well as lung-derived Calu-3 and A549 cells. The paucity of the innate human inhibitory microRNAs to bind to leader sequence of SARS-CoV-2 can contribute to its high replication in infected human cells.

scholarly journals Achilles' Heel of SARS-CoV-2: Transcription Regulatory Sequence and Leader Sequence in 5’ Untranslated Region have Unique Evolutionary Patterns and are Vital for Virus Replication in Infected Human Cells

2020 ◽  
Author(s):  
Manijeh Mohammadi‐Dehcheshmeh ◽  
Sadrollah Molaei Moghbeli ◽  
Samira Rahimirad ◽  
Ibrahim Alanazi ◽  
Zafer Saad Al Shehri ◽  
...  
Keyword(s):  
Virus Replication ◽  
Genomic Sequence ◽  
Genomic Structure ◽  
Human Cells ◽  
Leader Sequence ◽  
The Other ◽  
Regulatory Sequence ◽  
Evolutionary Patterns ◽  
Main Challenge ◽  
Missense Variation

Background SARS-CoV-2 has generated a life-treating pandemic and is the main challenge of this century. Some untranslated regions (UTRs) in SARS-CoV-2 genome, specifically leader sequence and transcription regulatory sequence (TRS) in 5&rsquo;UTR, can be considered as Achilles' heel of virus. Leader sequence are found at the 5' ends of all encoded transcripts that highlights its importance. TRS can explain the host range and pathogenicity of coronavirus. However, our knowledge on the evolution and the role of UTRs in SARS-CoV-2 pathogenicity is very limited. This study is a pioneering attempt to unravel the evolution of key regions in 5' UTR of SARS-CoV-2 and discover the inhibitory microRNAs against 5' UTR of virus. Methods Evolution of TRS and leader sequence was compared between human pathogenic (SARS-CoV-2, SARS, and MERS) and non-pathogenic (bovine) coronaviruses. Profiling of microRNAs that can inactive the key UTR regions of coronaviruses, UTR-inhibitory microRNAs, was carried out. Findings We found a distinguished pattern of evolution in leader sequence and TRS of SARS-CoV-2, compared to the other coronaviruses. Mining all available microRNA families against leader sequences of coronaviruses resulted in discovery of 39 microRNAs with an acceptable thermodynamic binding energy against SARS-COV-2, SARS, MERS, Bat Coronavirus, or Bovine Coronavirus. Multivariate analysis demonstrated a distinguished pattern of binding of leader sequence of SARS-CoV-2 against microRNAs, with a lower binding stability. hsa-MIR-5004-3p was the only human microRNA that can target leader sequence of SARS and SARS-CoV-2. However, its binding stability remarkably decreased in SARS-COV-2 (-19.4 kcal/mol), compared to SARS-COV-2 (-25.9 kcal/mol). We found an insertion-type mutation in leader sequence of SARS-COV-2 that results in lower binding stability and escaping of viral leader sequence from hsa-MIR-5004-3p. Altogether, we suggest lack of innate human inhibitory microRNAs to bind to leader sequence and TRS of SARS-CoV-2 contributes to its high replication in infected human cells. On the other hand, mining of two hundred million deposited human genomic variants led us to discovery of 49 missense and splice-disrupt mutations in genomic structure of hsa-MIR-5004-3p. These mutations can negatively affect hsa-MIR-5004-3p function in preventing SARS-CoV-2 replication. Interpretation This study unravels the evolution of key regions in 5&rsquo;UTR of SARS-CoV-2. Inducing microRNAs to bind to the leader sequence and TRS regions by drugs or food supplements can reduce virus replication. Enhancing the microRNA defence machinery against TRS and leader of virus has a potential to prevent SARS-CoV-2 infection at the first place. The mentioned strategy is rapidly achievable against COVID-19. Missense variation in genomic sequence of 5&rsquo;UTR inhibitory microRNAs, such as hsa-MIR-5004-3p, can be considered as risk factor of COVID-19.

Chronic Pain: Fundamental Scientific Considerations, Specifically for Legal Claims

2013 ◽  
Vol 18 (1) ◽  
pp. 1-18 ◽  
Author(s):  
Robert J. Barth
Keyword(s):  
Health Outcomes ◽  
Pain Perception ◽  
Driving Forces ◽  
Psychological Treatment ◽  
Dominant Role ◽  
Meta Analysis ◽  
General Medicine ◽  
Pain Syndrome ◽  
Problematic Relationship

Abstract Scientific findings have indicated that psychological and social factors are the driving forces behind most chronic benign pain presentations, especially in a claim context, and are relevant to at least three of the AMA Guides publications: AMA Guides to Evaluation of Disease and Injury Causation, AMA Guides to Work Ability and Return to Work, and AMA Guides to the Evaluation of Permanent Impairment. The author reviews and summarizes studies that have identified the dominant role of financial, psychological, and other non–general medicine factors in patients who report low back pain. For example, one meta-analysis found that compensation results in an increase in pain perception and a reduction in the ability to benefit from medical and psychological treatment. Other studies have found a correlation between the level of compensation and health outcomes (greater compensation is associated with worse outcomes), and legal systems that discourage compensation for pain produce better health outcomes. One study found that, among persons with carpal tunnel syndrome, claimants had worse outcomes than nonclaimants despite receiving more treatment; another examined the problematic relationship between complex regional pain syndrome (CRPS) and compensation and found that cases of CRPS are dominated by legal claims, a disparity that highlights the dominant role of compensation. Workers’ compensation claimants are almost never evaluated for personality disorders or mental illness. The article concludes with recommendations that evaluators can consider in individual cases.

Role of autophagy in hepatitis C virus replication

2019 ◽  
Author(s):  
WI Twu ◽  
K Tabata ◽  
D Paul ◽  
R Bartenschlager
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Replication

Effectiveness of psychological interventions to improve emotion regulation in youth - a meta-analysis

2019 ◽  
Author(s):  
Bettina Moltrecht ◽  
Jessica Deighton ◽  
Praveetha Patalay ◽  
Julian Childs
Keyword(s):  
Emotion Regulation ◽  
Emotion Dysregulation ◽  
Psychological Intervention ◽  
Meta Analysis ◽  
Age Groups ◽  
Effect Sizes ◽  
What Works ◽  
Large Heterogeneity ◽  
Larger Sample

Background: Research investigating the role of emotion regulation (ER) in the development and treatment of psychopathology has increased in recent years. Evidence suggests that an increased focus on ER in treatment can improve existing interventions. Most ER research has neglected young people, therefore the present meta-analysis summarizes the evidence for existing psychosocial intervention and their effectiveness to improve ER in youth. Methods: A systematic review and meta-analysis was conducted according to the PRISMA guidelines. Twenty-one randomized-control-trials (RCTs) assessed changes in ER following a psychological intervention in youth exhibiting various psychopathological symptoms.Results: We found moderate effect sizes for current interventions to decrease emotion dysregulation in youth (g=-.46) and small effect sizes to improve emotion regulation (g=0.36). Significant differences between studies including intervention components, ER measures and populations studied resulted in large heterogeneity. Conclusion: This is the first meta-analysis that summarizes the effectiveness for existing interventions to improve ER in youth. The results suggest that interventions can enhance ER in youth, and that these improvements correlate with improvements in psychopathology. More RCTs including larger sample sizes, different age groups and psychopathologies are needed to increase our understanding of what works for who and when.

Systematic review and meta-analysis of Altruistic and Game-playing Love

2020 ◽  
Author(s):  
Hossein Dabiriyan Tehrani ◽  
Sara Yamini
Keyword(s):  
Systematic Review ◽  
Subgroup Analysis ◽  
Meta Analysis ◽  
Game Playing ◽  
Love Styles ◽  
Collectivistic Culture ◽  
Meta Regression ◽  
Collectivistic Cultures ◽  
The Relationship

This systematic review aimed to find attitudes toward Altruistic and Game-playing love styles across individualistic and collectivistic cultures. Addressing major moderators concerning Altruistic and Game-playing love styles are the secondary objectives of this review. This review included 102 articles comprising samples from 37 countries (N = 41997). The findings of this meta-analysis show that there is a collectivistic and individualistic difference in Game-playing but not in the Altruistic love style. Collectivistic and individualistic cultures, on average, demonstrate the same perception concerning the Altruistic love style, whereas collectivistic culture shows the Game-playing love style more strongly. To explain the role of moderators in key measures, the subgroup analysis and meta-regression show that both Game-playing and Altruistic love styles decline by increasing the length of the relationship. Likewise, having children affects these love styles such that the Altruistic love style is improved, and the Game-playing love style is reduced by the presence of children in families.

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