scholarly journals Identification of a Coronavirus Transcription Enhancer

2008 ◽  
Vol 82 (8) ◽  
pp. 3882-3893 ◽  
Author(s):  
José L. Moreno ◽  
Sonia Zúñiga ◽  
Luis Enjuanes ◽  
Isabel Sola

ABSTRACT Coronavirus (CoV) transcription includes a discontinuous mechanism during the synthesis of sub-genome-length minus-strand RNAs leading to a collection of mRNAs in which the 5′ terminal leader sequence is fused to contiguous genome sequences. It has been previously shown that transcription-regulating sequences (TRSs) preceding each gene regulate transcription. Base pairing between the leader TRS (TRS-L) and the complement of the body TRS (cTRS-B) in the nascent RNA is a determinant factor during CoV transcription. In fact, in transmissible gastroenteritis CoV, a good correlation has been observed between subgenomic mRNA (sg mRNA) levels and the free energy (ΔG) of TRS-L and cTRS-B duplex formation. The only exception was sg mRNA N, the most abundant sg mRNA during viral infection in spite of its minimum ΔG associated with duplex formation. We postulated that additional factors should regulate transcription of sg mRNA N. In this report, we have described a novel transcription regulation mechanism operating in CoV by which a 9-nucleotide (nt) sequence located 449 nt upstream of the N gene TRS core sequence (CS-N) interacts with a complementary sequence just upstream of CS-N, specifically increasing the accumulation of sg mRNA N. Alteration of this complementarity in mutant replicon genomes showed a correlation between the predicted stability of the base pairing between 9-nt sequences and the accumulation of sg mRNA N. This interaction is exclusively conserved in group 1a CoVs, the only CoV subgroup in which the N gene is not the most 3′ gene in the viral genome. This is the first time that a long-distance RNA-RNA interaction regulating transcriptional activity specifically enhancing the transcription of one gene has been described to occur in CoVs.

2005 ◽  
Vol 79 (4) ◽  
pp. 2506-2516 ◽  
Author(s):  
Isabel Sola ◽  
José L. Moreno ◽  
Sonia Zúñiga ◽  
Sara Alonso ◽  
Luis Enjuanes

ABSTRACT The generation of subgenomic mRNAs in coronavirus involves a discontinuous mechanism of transcription by which the common leader sequence, derived from the genome 5′ terminus, is fused to the 5′ end of the mRNA coding sequence (body). Transcription-regulating sequences (TRSs) precede each gene and include a conserved core sequence (CS) surrounded by relatively variable sequences (5′ TRS and 3′ TRS). Regulation of transcription in coronaviruses has been studied by reverse-genetics analysis of the sequences immediately flanking a unique CS in the Transmissible gastroenteritis virus genome (CS-S2), located inside the S gene, that does not lead to detectable amounts of the corresponding mRNA, in spite of its canonical sequence. The transcriptional inactivity of CS-S2 was genome position independent. The presence of a canonical CS was not sufficient to drive transcription, but subgenomic synthesis requires a minimum base pairing between the leader TRS (TRS-L) and the complement of the body TRS (cTRS-B) provided by the CS and its adjacent nucleotides. A good correlation was observed between the free energy of TRS-L and cTRS-B duplex formation and the levels of subgenomic mRNA S2, demonstrating that base pairing between the leader and body beyond the CS is a determinant regulation factor in coronavirus transcription. In TRS mutants with increasing complementarity between TRS-L and cTRS-B, a tendency to reach a plateau in ΔG values was observed, suggesting that a more precise definition of the TRS limits might be proposed, specifically that it consists of the central CS and around 4 nucleotides flanking 5′ and 3′ the CS. Sequences downstream of the CS exert a stronger influence on the template-switching decision according to a model of polymerase strand transfer and template switching during minus-strand synthesis.


2020 ◽  
Vol 26 (45) ◽  
pp. 5783-5792
Author(s):  
Kholood Abid Janjua ◽  
Adeeb Shehzad ◽  
Raheem Shahzad ◽  
Salman Ul Islam ◽  
Mazhar Ul Islam

There is compelling evidence that drug molecules isolated from natural sources are hindered by low systemic bioavailability, poor absorption, and rapid elimination from the human body. Novel approaches are urgently needed that could enhance the retention time as well as the efficacy of natural products in the body. Among the various adopted approaches to meet this ever-increasing demand, nanoformulations show the most fascinating way of improving the bioavailability of dietary phytochemicals through modifying their pharmacokinetics and pharmacodynamics. Curcumin, a yellowish pigment isolated from dried ground rhizomes of turmeric, exhibits tremendous pharmacological effects, including anticancer activities. Several in vitro and in vivo studies have shown that curcumin mediates anticancer effects through the modulation (upregulation and/or downregulations) of several intracellular signaling pathways both at protein and mRNA levels. Scientists have introduced multiple modern techniques and novel dosage forms for enhancing the delivery, bioavailability, and efficacy of curcumin in the treatment of various malignancies. These novel dosage forms include nanoparticles, liposomes, micelles, phospholipids, and curcumin-encapsulated polymer nanoparticles. Nanocurcumin has shown improved anticancer effects compared to conventional curcumin formulations. This review discusses the underlying molecular mechanism of various nanoformulations of curcumin for the treatment of different cancers. We hope that this study will make a road map for preclinical and clinical investigations of cancer and recommend nano curcumin as a drug of choice for cancer therapy.


Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3758
Author(s):  
Joanna Smarkusz-Zarzecka ◽  
Lucyna Ostrowska ◽  
Joanna Leszczyńska ◽  
Karolina Orywal ◽  
Urszula Cwalina ◽  
...  

Use of probiotic supplements, the benefits of which have not been proven in sportspeople, is becoming more widespread among runners. The aim of this study was to evaluate the effect of a multi-strain probiotic on body composition, cardiorespiratory fitness and inflammation in the body. The randomised, double-blind study included 66 long-distance runners. The intervention factor was a multi-strain probiotic or placebo. At the initial and final stages of the study, evaluation of body composition and cardiorespiratory fitness was performed and the presence of inflammation determined. In the group of men using the probiotic, an increase in lean body mass (p = 0.019) and skeletal muscle mass (p = 0.022) was demonstrated, while in the group of women taking the probiotic, a decrease in the content of total body fat (p = 0.600) and visceral fat (p = 0.247) was observed. Maximum oxygen consumption (VO2max) increased in women (p = 0.140) and men (p = 0.017) using the probiotic. Concentration of tumour necrosis factor-alpha decreased in women (p = 0.003) and men (p = 0.001) using the probiotic and in women (p = 0.074) and men (p = 0.016) using the placebo. Probiotic therapy had a positive effect on selected parameters of body composition and cardiorespiratory fitness of study participants and showed a tendency to reduce inflammation.


2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
A Markovich ◽  
O Mironova

Abstract Funding Acknowledgements Type of funding sources: None. Background Regular physical activity is an important component of therapy for most сardiovascular diseases and is associated with reduced cardiovascular and all-cause mortality. The promotion of the physical activity and regular exercise is an important preventive measure that affects the prognosis. Purpose To assess the awareness of the prevalence of cardiovascular disease in exercising population and its influence on the safety of the patients and healthy adults among coaches and people actively engaged in sports activities. Methods An open non-randomized observation was conducted. The questionnaire created by our team included 45 questions about cardiovascular diseases and sport. 111 athletes and coaches aged from 19 to 46 were enrolled in the study. 61,5% (68) are men and 38,5% (42) of the respondents are women. 30,3% (33) of the respondents are coaches. 45,5% (15) of them have over 5 years of coaching experience. 44% (48) of all respondents prefer endurance sport, 25,7% (28) train strength exercise. 63,6% (70) train 3-8 hours per week, 12,7% (14 [7 women and 7 men]) train more than 8 hours each week. Results 18,5% (20 [6 women and 14 men]) think that ECG is enough for screening for cardiovascular diseases. 20% (4) of them are coaches. Only 69,5% (77) of all respondents know about treadmill test. And 41,6% (32/77) of them know about the necessary screening for arrhythmogenic condition. 13% (10/77) of them train more than 8 hours per week. And only 27,3% (21/77) of people who know about treadmill test, passed it themselves. Also 21,6% (24) of all respondents think that any episode of arrhythmia is the  contraindication for any sport. But 96,4% (107) of the respondents know that it is necessary to regularly screen the cardiovascular system, even in the absence of complaints. 9% (10) of the interviewed think that diet is not important for people with cardiovascular diseases. And 18,9% (21) of the respondents don’t know about the effect of electrolytes on the body and the work of the heart muscle. Only 53,2% (59 [21 women and 38 men]) of the respondents trust the doctors more than coaches or themselves. And this is one of the reasons why it is necessary to talk about the basic principles of sports cardiology not only to doctors. 8,1% (9) of the respondents have never heard about any cases of sudden death of an athlete during training or at competitions due to «heart problems». 63,6% (21) of the coaches would not train a person who has suffered a heart attack. 71,8% (56) of the sportsmen would like to return to training after a heart attack. Conclusions Despite the fact that most people prefer a sedentary lifestyle, high-intensity fitness and long-distance endurance sport is getting more popular. Our survey proves the relatively low level of education about the underlying health conditions and possible risks associated with sports not only among  athletes but  professional coaches as well. There are no conflicts of interest to declare.


2020 ◽  
Vol 11 (1) ◽  
pp. 147-160
Author(s):  
Leonardo Mariano Gomes ◽  
Rita Wu

AbstractIn this article, we present TouchYou, a pair of wearable interfaces that enable affective touch interactions with people at long-distance. Through a touch-sensitive interface, which works by touch, pressure and capacitance, the body becomes the own input for stimulating the other body, which has a stimulation interface that enables the feeling of being touched. The person receives an electrical muscle stimulation, thermal and mechanical stimulation that react depending on the touch sensed by the first interface. By using the TouchYou, people can stimulate each other, using their own body, not only for sexual relations at a distance but for the production of affection and another way of feeling. We discuss the importance of the touch for human relationships, the current state of the art in haptic interfaces and how the technology can be used for the affection remote transmission. We present the design process of the TouchYou sensitive and stimulation interfaces, with a contribution of a method for developing custom touch sensors, we explore usage scenarios for the technology, including sex toys and sex robots and we present the concept of using the body as a remote sex interface.


mSystems ◽  
2018 ◽  
Vol 3 (5) ◽  
Author(s):  
Matthew D. Servinsky ◽  
Rebecca L. Renberg ◽  
Matthew A. Perisin ◽  
Elliot S. Gerlach ◽  
Sanchao Liu ◽  
...  

ABSTRACTBacterial fermentation of carbohydrates from sustainable lignocellulosic biomass into commodity chemicals by the anaerobic bacteriumClostridium acetobutylicumis a promising alternative source to fossil fuel-derived chemicals. Recently, it was demonstrated that xylose is not appreciably fermented in the presence of arabinose, revealing a hierarchy of pentose utilization in this organism (L. Aristilde, I. A. Lewis, J. O. Park, and J. D. Rabinowitz, Appl Environ Microbiol 81:1452–1462, 2015,https://doi.org/10.1128/AEM.03199-14). The goal of the current study is to characterize the transcriptional regulation that occurs and perhaps drives this pentose hierarchy. Carbohydrate consumption rates showed that arabinose, like glucose, actively represses xylose utilization in cultures fermenting xylose. Further, arabinose addition to xylose cultures led to increased acetate-to-butyrate ratios, which indicated a transition of pentose catabolism from the pentose phosphate pathway to the phosphoketolase pathway. Transcriptome sequencing (RNA-Seq) confirmed that arabinose addition to cells actively growing on xylose resulted in increased phosphoketolase (CA_C1343) mRNA levels, providing additional evidence that arabinose induces this metabolic switch. A significant overlap in differentially regulated genes after addition of arabinose or glucose suggested a common regulation mechanism. A putative open reading frame (ORF) encoding a potential catabolite repression phosphocarrier histidine protein (Crh) was identified that likely participates in the observed transcriptional regulation. These results substantiate the claim that arabinose is utilized preferentially over xylose inC. acetobutylicumand suggest that arabinose can activate carbon catabolite repression via Crh. Furthermore, they provide valuable insights into potential mechanisms for altering pentose utilization to modulate fermentation products for chemical production.IMPORTANCEClostridium acetobutylicumcan ferment a wide variety of carbohydrates to the commodity chemicals acetone, butanol, and ethanol. Recent advances in genetic engineering have expanded the chemical production repertoire ofC. acetobutylicumusing synthetic biology. Due to its natural properties and genetic engineering potential, this organism is a promising candidate for converting biomass-derived feedstocks containing carbohydrate mixtures to commodity chemicals via natural or engineered pathways. Understanding how this organism regulates its metabolism during growth on carbohydrate mixtures is imperative to enable control of synthetic gene circuits in order to optimize chemical production. The work presented here unveils a novel mechanism via transcriptional regulation by a predicted Crh that controls the hierarchy of carbohydrate utilization and is essential for guiding robust genetic engineering strategies for chemical production.


2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Yan Chen ◽  
Yan-Jun Wang ◽  
Ying Zhao ◽  
Jin-Cheng Wang

Diabetic nephropathy (DN) is one of the most devastating complications of diabetes mellitus. Carbohydrate response element binding protein (ChREBP) is a basic helix–loop–helix leucine zipper transcription factor that primarily mediates glucose homeostasis in the body. The present study investigated the role of ChREBP in the pathogenesis of DN. The expression of ChREBP was detected in patients with type 2 diabetes mellitus (T2DM), diabetic mice, and mesangial cells. ELISA was used to measure cytokine production in mesangial cells. Flow cytometry analysis was performed to detect the apoptosis of mesangial cells in the presence of high glucose. The expression levels of ChREBP and several cytokines (TNF-α, IL-1β, and IL-6) were up-regulated in T2DM patients. The mRNA and protein levels of ChREBP were also significantly elevated in the kidneys of diabetic mice. Moreover, glucose treatment promoted mRNA levels of TNF-α, IL-1β, and IL-6 in mesangial cells. Glucose stimulation induced significant apoptosis of SV40 MES 13 cells. In addition, transfection with ChREBP siRNA significantly inhibited ChREBP expression. Consequently, the inflammatory responses and apoptosis were inhibited in SV40 MES 13 cells. These results demonstrated that ChREBP could mediate the inflammatory response and apoptosis of mesangial cells, suggesting that ChREBP may be involved in the pathogenesis of DN.


2018 ◽  
Vol 59 (1) ◽  
pp. 48-60 ◽  
Author(s):  
P S Segre ◽  
D E Cade ◽  
J Calambokidis ◽  
F E Fish ◽  
A S Friedlaender ◽  
...  

Abstract Blue whales are often characterized as highly stable, open-ocean swimmers who sacrifice maneuverability for long-distance cruising performance. However, recent studies have revealed that blue whales actually exhibit surprisingly complex underwater behaviors, yet little is known about the performance and control of these maneuvers. Here, we use multi-sensor biologgers equipped with cameras to quantify the locomotor dynamics and the movement of the control surfaces used by foraging blue whales. Our results revealed that simple maneuvers (rolls, turns, and pitch changes) are performed using distinct combinations of control and power provided by the flippers, the flukes, and bending of the body, while complex trajectories are structured by combining sequences of simple maneuvers. Furthermore, blue whales improve their turning performance by using complex banked turns to take advantage of their substantial dorso-ventral flexibility. These results illustrate the important role body flexibility plays in enhancing control and performance of maneuvers, even in the largest of animals. The use of the body to supplement the performance of the hydrodynamically active surfaces may represent a new mechanism in the control of aquatic locomotion.


Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1421
Author(s):  
Valentina S. Evsiukova ◽  
Elizabeth A. Kulikova ◽  
Alexander V. Kulikov

Short-lived turquoise killifish (Nothobranchius furzeri) have become a popular model organism for neuroscience. In the present paper we study for the first time their behavior in the novel tank diving test and the levels of mRNA of various 5-HT-related genes in brains of 2-, 4- and 6-month-old males and females of N. furzeri. The marked effect of age on body mass, locomotor activity and the mRNA level of Tph1b, Tph2, Slc6a4b, Mao, Htr1aa, Htr2a, Htr3a, Htr3b, Htr4, Htr6 genes in the brains of N. furzeri males was shown. Locomotor activity and expression of the Mao gene increased, while expression of Tph1b, Tph2, Slc6a4b, Htr1aa, Htr2a, Htr3a, Htr3b, Htr4, Htr6 genes decreased in 6-month-old killifish. Significant effects of sex on body mass as well as on mRNA level of Tph1a, Tph1b, Tph2, Slc6a4b, Htr1aa, 5-HT2a, Htr3a, Htr3b, Htr4, and Htr6 genes were revealed: in general both the body mass and the expression of these genes were higher in males. N. furzeri is a suitable model with which to study the fundamental problems of age-related alterations in various mRNA levels related with the brains 5-HT system.


2022 ◽  
Vol 2022 ◽  
pp. 1-13
Author(s):  
Qiao Chen ◽  
Shihong Liu

Sports can cause the consumption of energy materials in the body. The rational use of nutritional supplements can maintain the homeostasis of the organism, which plays a very important role in improving the competitive performance of sports athletes. The purpose of this study is to explore the effect of nutritional supplements on basketball sports fatigue. The method of this study is as follows: first of all, 15 basketball players in our city were selected as the experimental objects, and they were randomly divided into the experimental group and the control group. The members of the experimental group took nutrients. After the training, 6 days a week, 3 hours in the morning and 3 hours in the afternoon, and the rest was adjusted on Sunday. Before training, four weeks and eight weeks of training, the blood routine indexes and body functions of athletes were tested. The results showed that the number of red blood cells, hemoglobin concentration, and average hemoglobin concentration of ligustilide supplement of the athletes were at the level of 0.05 after 4 weeks and 8 weeks, and the difference was significant ( P < 0.05 ). The nutritional supplements were used in sprint (3.4 s less), long-distance running (12.8 s less), and weight lifting (6.2 kg more) to a certain extent. Nutritional supplements are used as an auxiliary means of diet to supplement the amino acids, trace elements, vitamins, minerals, etc. required by the human body. The conclusion is that nutrition supplement can effectively improve the indexes of athletes’ body in about four weeks, but the effect is not obvious after a long time. This study provides a certain method for the research of nutritional supplements in the field of sports.


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