A member of the Y-box protein family interacts with an upstream element in the α1(I) collagen gene

Transforming growth factor beta (TGF-β) stimulates protein complex formation on a TGF-β response element (TAE) found in the distal portion (−1624) of the collagen alpha 1(I) promoter. To identify the fibroblast proteins in this complex, an expression library constructed from human embryonic lung fibroblasts mRNA was screened using a tetramer of TAE. Y-box binding protein (YB-1), was identified as a protein in the TAE–protein complex. The protein expressed by phage clones formed a specific complex with labeled TAE but not mutated TAE (mTAE) similar to the complex formed with nuclear protein. Nuclear protein–TAE complexes isolated from native gels contained YB-1 by Western analysis. TGF-β treatment increased the amount of YB-1 protein in nuclear extracts, decreased its amount in cytoplasm, but did not alter the steady state levels of YB-1 mRNA. A full-length YB-1 protein expressed in human lung fibroblasts was primarily located in the nucleus with punctate staining in cytoplasmic regions. The expression of YB-1 decreased in the cytoplasm after 2 h of TGF-β treatment. Therefore, the increased binding activity seen in TGF-β-stimulated nuclear extracts was due primarily to relocalization of YB-1 from the cytoplasm to the nuclear compartment. Co-transfection of YB-1 cDNA with a collagen promoter–reporter construct caused a dose-dependent activation of collagen promoter activity in rat fibroblasts whereas the promoter with a mutation in the TAE element was not sensitive to YB-1 co-expression. In conclusion, we have identified YB-1 as a protein that interacts with a TGF-β response element in the distal region of the collagen alpha 1(I) gene. YB-1 protein activates the collagen promoter and translocates into the nucleus during TGF-β addition to fibroblasts, suggesting a role for this protein in TGF-β signaling.     

Sex differences in aging,life span and spontaneous tumorigenesis in 129/Sv mice neonatally exposed to metformin

The perinatal (prenatal and early neonatal) period is a critical stage for hypothalamic programming of sexual differentiation as well as for the development of energy and metabolic homeostasis. We hypothesized that neonatal treatment with antidiabetic drug biguanide metformin would positively modify regulation of growth hormone – IGF-1 – insulin signaling pathway slowing down aging and improving cancer preventive patterns in rodents. To test this hypothesis male and female 129/Sv mice were s.c. injected with metformin (100 mg/kg) at the 3rd, 5th and 7th days after birth. Metformin-treated males consumed less food and water and their body weight was decreased as compared with control mice practically over their entire lifespan. There were no significant differences in age-related dynamics of food and water consumption in females and they were heavier than controls. The fraction of mice with regular estrous cycles decreased with age and demonstrated a tendency to decrease in the females neonatally treated with metformin. Neonatal exposure to metformin practically failed to change the extent of hormonal and metabolic parameters in blood serum of male and female mice. In males, neonatal metformin treatment significantly increased the mean life span (+20%, P < 0.05) and slightly increased the maximum life span (+3.5%). In females, the mean life span and median in metformin-treated groups were slightly decreased (−9.1% and −13.8% respectively, P > 0.05) in comparison to controls, whereas mean life span of last 10% survivors and maximum life span were the same as in controls. Almost half (45%) of control male mice and 71.8% male mice neonatally exposed to metformin survived up to 800 d of age, the same age was achieved by 54.3% of mice in control female group and 30% of metformin-treated females (P < 0.03). Thus, neonatal metformin exposure slows down aging and prolongs lifespan in male but not in female mice.     

Repercussions of the COVID-19 pandemic on athletes: a cross-sectional study

The COVID-19 pandemic has presented significant challenges and implications for the sports community. Thus, this study aimed to describe the prevalence of COVID-19 in Brazilian athletes and identify the epidemiological, clinical, athletic, life and health factors associated with the disease in these individuals. A cross-sectional study was performed involving 414 athletes from 22 different sports using an online questionnaire from August to November 2020. The association between the athletes’ characteristics and COVID-19 was evaluated using a logistic regression model. The prevalence of COVID-19 was 8.5%, although only 40% of athletes reported having been tested. Being under 27 years of age (3-fold), having children (~5-fold), having a teammate test positive for COVID-19 (2.5-fold), and smoking (14-fold) were associated with a possible higher risk of disease. Almost 20% of athletes self-reported musculoskeletal injuries during the period of the pandemic that was studied. Athletes with a university education (P = 0.02), a profession other than sports (P < 0.001), those from a low-income family (P = 0.01), and public health system users (P = 0.04) were significantly less frequently tested for COVID-19, whereas international competitors, athletes who received a wage, and athletes who had a teammate who tested positive for COVID-19 were 2-, 3-, and 15-fold more likely to be tested for COVID-19, respectively. Approximately 26% of the athletes who tested negative or were untested reported more than three characteristic COVID-19 symptoms, and 11% of athletes who tested positive for COVID-19 were asymptomatic. The identification of modifiable (have children, smoking, and teammates positively tested) and non-modifiable (age under 27 years) factors related to COVID-19 in athletes can contribute to implementing surveillance programmes to decrease the incidence of COVID-19 in athletes and its negative impacts in sports.     

Summer distribution of the purplegray sculpin <Emphasis Type="Italic">Gymnocanthus detrisus</Emphasis> (Cottidae) in Waters of Primorsky Krai,Sea of Japan

Results of trawl catches show that in the summer period, in the waters of Primorsky Krai, Russia, Sea of Japan, the purplegray sculpin Gymnocanthus detrisus occurs at depths of 20 to 411 m, preferring the range 80–250 m. The temperature of the species’ habitat varies from 0.8 to 8.6 ° C, and the optimal one is 1.2–2.2 °C. G. detrisus occurs at the preferred depths more frequently in the southern area—the Peter the Great Bay, which is more favorable for foraging; in the area of North Primorsky Krai it was found both at greater and lesser depths. The latter is probably determined by the more limited spreading of waters with unsuitable temperatures for the species there. The body size of the purplegray sculpin grows with depth. Juveniles avoid depths over 200 m, where inflow of low-temperature waters is recorded. G. detrisus, which inhabits waters of Primorsky Krai, is represented mainly by females; the proportion of males exceeds that of females only in the 21–27 cm size group. This may be related to the lower growth rate in males after maturation as compared to females.     

Correlated evolution of interacting proteins: looking behind the mirrortree

It has been observed that the evolutionary distances of interacting proteins often display a higher level of similarity than those of noninteracting proteins. This finding indicates that interacting proteins are subject to common evolutionary constraints and constitutes the basis of a method to predict protein interactions known as mirrortree. It has been difficult, however, to identify the direct cause of the observed similarities between evolutionary trees. One possible explanation is the existence of compensatory mutations between partners' binding sites to maintain proper binding. This explanation, though, has been recently challenged, and it has been suggested that the signal of correlated evolution uncovered by the mirrortree method is unrelated to any correlated evolution between binding sites. We examine the contribution of binding sites to the correlation between evolutionary trees of interacting domains. We show that binding neighborhoods of interacting proteins have, on average, higher coevolutionary signal compared with the regions outside binding sites; however, when the binding neighborhood is removed, the remaining domain sequence still contains some coevolutionary signal. In conclusion, the correlation between evolutionary trees of interacting domains cannot exclusively be attributed to the correlated evolution of the binding sites or to common evolutionary pressure exerted on the whole protein domain sequence, each of which contributes to the signal measured by the mirrortree approach.     

Structural and Functional Roles of Coevolved Sites in Proteins

Background

Understanding the residue covariations between multiple positions in protein families is very crucial and can be helpful for designing protein engineering experiments. These simultaneous changes or residue coevolution allow protein to maintain its overall structural-functional integrity while enabling it to acquire specific functional modifications. Despite the significant efforts in the field there is still controversy in terms of the preferable locations of coevolved residues on different regions of protein molecules, the strength of coevolutionary signal and role of coevolution in functional diversification.

Methodology

In this paper we study the scale and nature of residue coevolution in maintaining the overall functionality and structural integrity of proteins. We employed a large scale study to investigate the structural and functional aspects of coevolved residues. We found that the networks representing the coevolutionary residue connections within our dataset are in general of ‘small-world’ type as they have clustering coefficient values higher than random networks and also show smaller mean shortest path lengths similar and/or lower than random and regular networks. We also found that altogether 11% of functionally important sites are coevolved with any other sites. Active sites are found more frequently to coevolve with any other sites (15%) compared to protein (11%) and ligand (9%) binding sites. Metal binding and active sites are also found to be more frequently coevolved with other metal binding and active sites, respectively. Analysis of the coupling between coevolutionary processes and the spatial distribution of coevolved sites reveals that a high fraction of coevolved sites are located close to each other. Moreover, ∼80% of charge compensatory substitutions within coevolved sites are found at very close spatial proximity (< = 5Å), pointing to the possible preservation of salt bridges in evolution.

Conclusion

Our findings show that a noticeable fraction of functionally important sites undergo coevolution and also point towards compensatory substitutions as a probable coevolutionary mechanism within spatially proximal coevolved functional sites.