scholarly journals “Vaccine-Induced Covid-19 Mimicry” Syndrome:Splice reactions within the SARS-CoV-2 Spike open reading frame result in Spike protein variants that may cause thromboembolic events in patients immunized with vector-based vaccines

2021 ◽  
Author(s):  
Eric Kowarz ◽  
Lea Krutzke ◽  
Jenny Reis ◽  
Silvia Bracharz ◽  
Stefan Kochanek ◽  
...  
Keyword(s):  
Side Effects ◽  
Underlying Disease ◽  
Open Reading Frames ◽  
Spike Protein ◽  
Severe Side Effect ◽  
Thromboembolic Events ◽  
Reading Frame ◽  
Vein Thrombosis ◽  
Vaccination Campaigns ◽  
Protein Variants

Abstract During the last months many countries have started the immunization of millions of people by using vector-based vaccines. Unfortunately, severe side effects became overt during these vaccination campaigns: cerebral venous sinus thromboses (CVST), absolutely rare under normal life conditions, were found as a severe side effect that occured 4-14 days after first vaccinations. Besides CVST, Splanchnic Vein Thrombosis (SVT) was also observed. This type of adverse event has not been observed in the clinical studies of AstraZeneca, and therefore led immediately to a halt in vaccinations in several european countries. These events were mostly associated with thrombocytopenia, and thus, similar to the well-known Heparin-induced thrombo­cytopenia (HIT). Meanwhile, scientists have proposed a mechanism to explain this vaccine-induced thrombocytopenia. However, they do not provide a satisfactory explanation for the late thromboembolic events. Here, we present data that may explain these severe side effects which have been attributed to adenoviral vaccines. According to our results, transcription of wildtype and codon-optimized Spike open reading frames enables alternative splice events that lead to C-terminal truncated, soluble Spike protein variants. These soluble Spike variants may initiate severe side effects when binding to ACE2-expressing endothelial cells in blood vessels. In analogy to the thromboembolic events caused by Spike protein encoded by the SARS-CoV-2 virus, we termed the underlying disease mechanism the “Vaccine-Induced Covid-19 Mimicry” syndrome (VIC19M syndrome).

scholarly journals Recurrence of Upper Extremity Deep Vein Thrombosis Secondary to COVID-19

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 878
Author(s):  
Yesha H. Parekh ◽  
Nicole J. Altomare ◽  
Erin P. McDonnell ◽  
Martin J. Blaser ◽  
Payal D. Parikh
Keyword(s):  
Deep Vein Thrombosis ◽  
Lower Extremity ◽  
Upper Extremity ◽  
Thromboembolic Events ◽  
Vein Thrombosis ◽  
Venous Thromboembolic Events ◽  
Venous Thromboembolic ◽  
Deep Vein

Infection with SARS-CoV-2 leading to COVID-19 induces hyperinflammatory and hypercoagulable states, resulting in arterial and venous thromboembolic events. Deep vein thrombosis (DVT) has been well reported in COVID-19 patients. While most DVTs occur in a lower extremity, involvement of the upper extremity is uncommon. In this report, we describe the first reported patient with an upper extremity DVT recurrence secondary to COVID-19 infection.

scholarly journals Translational and Structural Requirements of the Early Nodulin Gene enod40, a Short-Open Reading Frame-Containing RNA, for Elicitation of a Cell-Specific Growth Response in the Alfalfa Root Cortex

2001 ◽  
Vol 21 (1) ◽  
pp. 354-366 ◽  
Author(s):  
Carolina Sousa ◽  
Christina Johansson ◽  
Celine Charon ◽  
Hamid Manyani ◽  
Christof Sautter ◽  
...  
Keyword(s):  
Amino Acids ◽  
Biological Activity ◽  
Rna Structure ◽  
Open Reading Frames ◽  
In Vitro Translation ◽  
Cortical Cells ◽  
Root Cortex ◽  
Reading Frame ◽  
Early Nodulin

ABSTRACT A diversity of mRNAs containing only short open reading frames (sORF-RNAs; encoding less than 30 amino acids) have been shown to be induced in growth and differentiation processes. The early nodulin geneenod40, coding for a 0.7-kb sORF-RNA, is expressed in the nodule primordium developing in the root cortex of leguminous plants after infection by symbiotic bacteria. Ballistic microtargeting of this gene into Medicago roots induced division of cortical cells. Translation of two sORFs (I and II, 13 and 27 amino acids, respectively) present in the conserved 5′ and 3′ regions ofenod40 was required for this biological activity. These sORFs may be translated in roots via a reinitiation mechanism. In vitro translation products starting from the ATG of sORF I were detectable by mutating enod40 to yield peptides larger than 38 amino acids. Deletion of a Medicago truncatula enod40 region between the sORFs, spanning a predicted RNA structure, did not affect their translation but resulted in significantly decreased biological activity. Our data reveal a complex regulation of enod40action, pointing to a role of sORF-encoded peptides and structured RNA signals in developmental processes involving sORF-RNAs.

Silencing the virus? Government communication and MMR vaccination campaigns – the Australian case

2021 ◽  
pp. 2046147X2110140
Author(s):  
Roumen Dimitrov
Keyword(s):  
Side Effects ◽  
Health Workers ◽  
Winning Strategy ◽  
Herd Immunity ◽  
Actor Network Theory ◽  
Strategic Communication ◽  
Long Run ◽  
Australian Case ◽  
Negative Side Effects ◽  
Vaccination Campaigns

In this paper I analyse a series of Australian MMR (measles-mumpsrubella) vaccination campaigns and policies from the last decade. Using the Bruno Latour’s Actor Network Theory (ATN), I locate human and non-human mediators – including the virus and vaccine – in the complex pro-vaccination alliance led by government campaigners. I identify the vaccine hesitant parents – a large group that ‘sits on the fence’ between the ‘vaccine confident’ and ‘vaccine refusing’ parents – as the main target of pro-vaccination campaigns. PR literature on pro-vaccination campaigns has applied ATN to the independence of the media as network agents. This paper contributes with the problematisation of several more actors such as the health workers, medical experts and the vaccine hesitant parents themselves. Even when they are keen members of a pro-vaccination network, they cannot be taken for granted. This is where understanding of stigma, silence and voice helps. To align their group interests and discourses, government should know how to communicate strategically – including how to communicate indirectly, avoiding stigma and keeping certain internal affinities and communicative distances intact. In conclusion, I make suggestions about strategic communication in pro-vaccination campaigns. Communication of statistical risks and side effects should be central. It is a winning strategy because it establishes a more credible balance between individual rights and collective obligations in achieving herd immunity. And mandating vaccination cannot replace communication. Research shows that legislating compulsory vaccination may have short-term and relatively small effects. They are almost negligible in the long run. Mandate may trigger compliance, but it also causes anger and mistrust. Mandating vaccine has negative side effects. It punishes with economic and cultural sanctions the socially disadvantaged, who are not active refusers. It also has the opposite effect on vaccine hesitant parents. It does not weaken but rather strengthens their resistance to the vaccine and pushes them to the lager of antivaxxers.

The positive regulatory function of the 5'-proximal open reading frames in GCN4 mRNA can be mimicked by heterologous, short coding sequences

1988 ◽  
Vol 8 (9) ◽  
pp. 3827-3836
Author(s):  
N P Williams ◽  
P P Mueller ◽  
A G Hinnebusch
Keyword(s):  
Translational Control ◽  
Normal Growth ◽  
Regulatory Elements ◽  
Growth Conditions ◽  
Open Reading Frames ◽  
Regulatory Function ◽  
Yeast Saccharomyces Cerevisiae ◽  
Reading Frame ◽  
Yeast Genes ◽  
Reading Frames

Translational control of GCN4 expression in the yeast Saccharomyces cerevisiae is mediated by multiple AUG codons present in the leader of GCN4 mRNA, each of which initiates a short open reading frame of only two or three codons. Upstream AUG codons 3 and 4 are required to repress GCN4 expression in normal growth conditions; AUG codons 1 and 2 are needed to overcome this repression in amino acid starvation conditions. We show that the regulatory function of AUG codons 1 and 2 can be qualitatively mimicked by the AUG codons of two heterologous upstream open reading frames (URFs) containing the initiation regions of the yeast genes PGK and TRP1. These AUG codons inhibit GCN4 expression when present singly in the mRNA leader; however, they stimulate GCN4 expression in derepressing conditions when inserted upstream from AUG codons 3 and 4. This finding supports the idea that AUG codons 1 and 2 function in the control mechanism as translation initiation sites and further suggests that suppression of the inhibitory effects of AUG codons 3 and 4 is a general consequence of the translation of URF 1 and 2 sequences upstream. Several observations suggest that AUG codons 3 and 4 are efficient initiation sites; however, these sequences do not act as positive regulatory elements when placed upstream from URF 1. This result suggests that efficient translation is only one of the important properties of the 5' proximal URFs in GCN4 mRNA. We propose that a second property is the ability to permit reinitiation following termination of translation and that URF 1 is optimized for this regulatory function.

Safety and Tolerability of Fluconazole in Children

1999 ◽  
Vol 43 (8) ◽  
pp. 1955-1960 ◽  
Author(s):  
Vas Novelli ◽  
Helen Holzel
Keyword(s):  
Side Effects ◽  
Safety Profile ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Pediatric Population ◽  
Gastrointestinal Symptoms ◽  
Underlying Disease ◽  
Severe Underlying Disease ◽  
Excellent Safety Profile ◽  
Concomitant Medications

ABSTRACT The safety profile of fluconazole was assessed for 562 children (ages, 0 to 17 years) comprising 323 males and 239 females. The data are derived from 12 clinical studies of fluconazole as prophylaxis or treatment for a variety of fungal infections in predominantly immunocompromised patients. Most children received multiple doses of fluconazole in the range of 1 to 12 mg/kg of body weight; a few received single doses. Administration was mainly by oral suspension or intravenous injection. Overall, 58 (10.3%) children reported 80 treatment-related side effects. The most common side effects were associated with the gastrointestinal tract (7.7%) or skin (1.2%). Self-limiting, treatment-related side effects affecting the liver and biliary system were reported in three patients (0.5%). Overall, 18 patients (3.2%) discontinued treatment due to side effects, mainly gastrointestinal symptoms. Dose and age did not appear to influence the incidence and pattern of side effects. Treatment-related laboratory abnormalities were uncommon, the most frequent being transient elevated alanine aminotransferase (4.9%), aspartate aminotransferase (2.7%), and alkaline phosphatase (2.3%) levels. Although 98.6% of patients were taking concomitant medications, no clinical or laboratory interactions were observed. The safety profile of fluconazole was compared with those of other antifungal agents, mostly oral polyenes, by using a subset of data from five controlled studies. Side effects were reported by more patients treated with fluconazole (45 of 382; 11.8%) than by those patients treated with comparable agents (25 of 381; 6.6%); vomiting and diarrhea were the most common events in both groups. The incidence and type of treatment-related laboratory abnormalities were similar for the two groups. In conclusion, fluconazole was well tolerated by the pediatric population, many of whom were suffering from severe underlying disease and were taking a variety of concurrent medications. The safety profile of fluconazole in children mirrors the excellent safety profile seen in adults.

scholarly journals Combination oral contraceptives – a practice-guided overview of everyday problems and their solutions

2020 ◽  
pp. 30-32
Author(s):  
DW Wolmarans ◽  
L Brand ◽  
SF Steyn
Keyword(s):  
Deep Vein Thrombosis ◽  
Side Effects ◽  
Adverse Effects ◽  
Oral Contraceptives ◽  
Cardiovascular Events ◽  
Treatment Withdrawal ◽  
Vein Thrombosis ◽  
Withdrawal Of Therapy ◽  
Deep Vein ◽  
Everyday Problems

Combination oral contraceptives (COCs) are some of the most commonly prescribed drugs for women between the ages of 15–451 and while they are accepted to be safe and highly effective, their use is often associated with a number of minor sideeffects. Considering the limited nature of this review, a detailed overview of the complete clinical profile of COCs falls beyond the current scope. Rather, we will focus on the most frequently reported side-effects of COCs that do not necessitate treatment withdrawal. Adverse effects that require immediate withdrawal of therapy are usually related to deep vein thrombosis (DVT) and other cardiovascular events, malignancies or hepatic pathology2 and would require a more in-depth review.

scholarly journals Persistence of ambigrammatic narnaviruses requires translation of the reverse open reading frame

2021 ◽  
Author(s):  
Hanna Retallack ◽  
Katerina D. Popova ◽  
Matthew T. Laurie ◽  
Sara Sunshine ◽  
Joseph L. DeRisi
Keyword(s):  
Viral Genome ◽  
Rna Viruses ◽  
Single Gene ◽  
Ribosome Profiling ◽  
Open Reading Frames ◽  
Reading Frame ◽  
Infected Cells ◽  
The Cost ◽  
Overlapping Open Reading Frames ◽  
First Time

Narnaviruses are RNA viruses detected in diverse fungi, plants, protists, arthropods and nematodes. Though initially described as simple single-gene non-segmented viruses encoding RNA-dependent RNA polymerase (RdRp), a subset of narnaviruses referred to as “ambigrammatic” harbor a unique genomic configuration consisting of overlapping open reading frames (ORFs) encoded on opposite strands. Phylogenetic analysis supports selection to maintain this unusual genome organization, but functional investigations are lacking. Here, we establish the mosquito-infecting Culex narnavirus 1 (CxNV1) as a model to investigate the functional role of overlapping ORFs in narnavirus replication. In CxNV1, a reverse ORF without homology to known proteins covers nearly the entire 3.2 kb segment encoding the RdRp. Additionally, two opposing and nearly completely overlapping novel ORFs are found on the second putative CxNV1 segment, the 0.8 kb “Robin” RNA. We developed a system to launch CxNV1 in a naïve mosquito cell line, then showed that functional RdRp is required for persistence of both segments, and an intact reverse ORF is required on the RdRp segment for persistence. Mass spectrometry of persistently CxNV1-infected cells provided evidence for translation of this reverse ORF. Finally, ribosome profiling yielded a striking pattern of footprints for all four CxNV1 RNA strands that was distinct from actively-translating ribosomes on host mRNA or co-infecting RNA viruses. Taken together, these data raise the possibility that the process of translation itself is important for persistence of ambigrammatic narnaviruses, potentially by protecting viral RNA with ribosomes, thus suggesting a heretofore undescribed viral tactic for replication and transmission. IMPORTANCE Fundamental to our understanding of RNA viruses is a description of which strand(s) of RNA are transmitted as the viral genome, relative to which encode the viral proteins. Ambigrammatic narnaviruses break the mold. These viruses, found broadly in fungi, plants, and insects, have the unique feature of two overlapping genes encoded on opposite strands, comprising nearly the full length of the viral genome. Such extensive overlap is not seen in other RNA viruses, and comes at the cost of reduced evolutionary flexibility in the sequence. The present study is motivated by investigating the benefits which balance that cost. We show for the first time a functional requirement for the ambigrammatic genome configuration in Culex narnavirus 1, which suggests a model for how translation of both strands might benefit this virus. Our work highlights a new blueprint for viral persistence, distinct from strategies defined by canonical definitions of the coding strand.

scholarly journals Determination of Platelets Parameters among People Vaccinated with Oxford-AstraZeneca Vaccine - COVID Vaccine at Khartoum State -Sudan

2021 ◽  
pp. 529-535
Author(s):  
Wafa Salah Eldein Ibrahim Mohamed ◽  
Elharam Ibrahim Abdallah ◽  
Alaa Eltayeb Omer ◽  
Lienda Bashier Eltayeb
Keyword(s):  
Statistical Analysis ◽  
Side Effects ◽  
Portal Vein ◽  
Portal Vein Thrombosis ◽  
Muscle Pain ◽  
Healthcare Providers ◽  
Vein Thrombosis ◽  
Significant Difference ◽  
And Gender

Background: The global SARS-CoV-2 vaccination program has been hampered by the rare-and initially inexplicable emergence of vaccine-associated thrombosis, particularly venous territory strokes or other venous obstructions, including portal vein thrombosis, which has been dubbed Vaccine-Induced Thrombotic Thrombocytopenia (VITT). So, this study was conducted to determine platelets parameters among people vaccinated with the AstraZeneca vaccine at Khartoum state. Materials & Methods: A total of 50 AstraZeneca vaccinated participants (22 male and 26 female) were utilized as a case and 50 healthy non-vaccinated participants (21 male and 29 female) were used as control. The age of both groups ranged between (20-62) years with a mean of 34.6 ± 11.9. Platelets parameters were assayed for all patients using Sysmex KX-21. Results: The statistical analysis was performed by using SPSS. The results of the study showed that there was no significant difference in platelets count and platelets indices when compared according to vaccine intake and gender. Also, the most frequent symptoms among vaccinated people were: muscle pain at the site of puncture (56%), fatigue (54%), fever (34%), headache (22%), nausea (16%), and diarrhea (6%) respectively and developed no symptoms (30%). Conclusions: The study concludes that the side effects of the COVID-19 AstraZeneca vaccine in Khartoum state, Sudan was consistent with the manufacturers’ data.  Healthcare providers and recipients of vaccines can be more confident about the safety of Oxford-AstraZeneca COVID-19 vaccines.

scholarly journals YeATS - a tool suite for analyzing RNA-seq derived transcriptome identifies a highly transcribed putative extensin in heartwood/sapwood transition zone in black walnut

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 155 ◽  
Author(s):  
Sandeep Chakraborty ◽  
Monica Britton ◽  
Jill Wegrzyn ◽  
Timothy Butterfield ◽  
Pedro José Martínez-García ◽  
...  
Keyword(s):  
Transition Zone ◽  
Transcript Abundance ◽  
Black Walnut ◽  
Open Reading Frames ◽  
Rna Seq ◽  
Reading Frame ◽  
Homologous Genes ◽  
Associated Proteins ◽  
Molecular Components ◽  
Reading Frames

The transcriptome provides a functional footprint of the genome by enumerating the molecular components of cells and tissues. The field of transcript discovery has been revolutionized through high-throughput mRNA sequencing (RNA-seq). Here, we present a methodology that replicates and improves existing methodologies, and implements a workflow for error estimation and correction followed by genome annotation and transcript abundance estimation for RNA-seq derived transcriptome sequences (YeATS - Yet Another Tool Suite for analyzing RNA-seq derived transcriptome). A unique feature of YeATS is the upfront determination of the errors in the sequencing or transcript assembly process by analyzing open reading frames of transcripts. YeATS identifies transcripts that have not been merged, result in broken open reading frames or contain long repeats as erroneous transcripts. We present the YeATS workflow using a representative sample of the transcriptome from the tissue at the heartwood/sapwood transition zone in black walnut. A novel feature of the transcriptome that emerged from our analysis was the identification of a highly abundant transcript that had no known homologous genes (GenBank accession: KT023102). The amino acid composition of the longest open reading frame of this gene classifies this as a putative extensin. Also, we corroborated the transcriptional abundance of proline-rich proteins, dehydrins, senescence-associated proteins, and the DNAJ family of chaperone proteins. Thus, YeATS presents a workflow for analyzing RNA-seq data with several innovative features that differentiate it from existing software.

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