BMI1 nuclear location is critical for RAD51-dependent response to replication stress and drives chemoresistance in breast cancer stem cells

Replication stress (RS) has a pivotal role in tumor initiation, progression, or therapeutic resistance. In this study, we depicted the mechanism of breast cancer stem cells’ (bCSCs) response to RS and its clinical implication. We demonstrated that bCSCs present a limited level of RS compared with non-bCSCs in patient samples. We described for the first time that the spatial nuclear location of BMI1 protein triggers RS response in breast cancers. Hence, in bCSCs, BMI1 is rapidly located to stalled replication forks to recruit RAD51 and activate homologous-recombination machinery, whereas in non-bCSCs BMI1 is trapped on demethylated 1q12 megasatellites precluding effective RS response. We further demonstrated that BMI1/RAD51 axis activation is necessary to prevent cisplatin-induced DNA damage and that treatment of patient-derived xenografts with a RAD51 inhibitor sensitizes tumor-initiating cells to cisplatin. The comprehensive view of replicative-stress response in bCSC has profound implications for understanding and improving therapeutic resistance.Subject terms: Breast cancer, Cancer stem cells     

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.     

Analysis of genotypic diversity inCercospora beticola Sacc. field isolates

Genetic variability and population structure ofCercospora beticola, the causal agent of Cercospora leaf spot in sugarbeet, from four sugarbeet-growing regions of Greece were investigated using growth rate, pathogenicity, and mini- and microsatellite DNA fingerprinting. Mycelial growth and pathogenicity were very diverse within and between groups, and no correlation was found between these features and the geographic origin of the isolates. High diversity was found by micro- and minisatellite fingerprinting, with an average gene diversity of 0.21, and no significant differences among populations. Among the 46 isolates, 45 different genotypes were identified, showing a high degree of genotype diversity. Analysis of the genetic profiles provided no evidence for regional patterns of variation (ΦF_ST=0.01, P=0.261) and the analysis of molecular variation (AMOVA) revealed that genetic variability was due mainly to variations within (99%) rather than between (1%) populations. Such a low level of genetic differentiation is reflected by a migration rate value Nm of 4.7. The high migration rate cannot be referred to splash dispersed conidia. To justify the absence of a regional structure in these C.beticola populations, we must suppose the existence of a long-distance means of dispersal, such as seed transmission and/or man mediated transmission.     

On the expression of cytokeratins and their distribution in some rabbit gland tissues.

The composition and distribution of cytokeratins were studied in a series of exocrine and endocrine glands in the rabbit, by means of anti-human monoclonal antibodies. Rabbit cytokeratins are known to be homologous to those in man, and their in situ distribution was also found to be similar. In acinic cells of the exocrine glands, only cytokeratins 8 and 18 were detected, whereas in ductal cells 1, 5, 10, 11 and 13, 19 were also present. The myoepithelial cells surrounding acini and basal duct cells were stained with the antibodies directed against cytokeratins 13 and 1, 5, 10, 11. Among the endocrine glands, a higher reactivity was observed in the thyroid gland and pancreatic islets, while pituitary and adrenal gland often remained unstained. Although the expression of cytokeratins was found to be almost homogeneous in each glandular cell type, a certain variability was observed, depending on the organ examined and the treatment carried out.     

A histological and immunohistochemical study of the effects of N-acetyl cysteine on retinopathy of prematurity by modifying insulin-like growth factor-1

Retinopathy of prematurity (ROP) is a vasoproliferative disorder that occurs in premature infants and may lead to permanent visual impairment. We investigated both the possible protective role of N-acetyl cysteine (NAC) for preventing ROP and the role of IGF-1 in the disorder. Forty-five newborn rats were divided into three groups. Group 1 was raised in room air as controls. Group 2 was exposed to 60% oxygen for 14 days after birth, then transferred to room air. Group 3 was exposed to the same conditions as group 2, but received intraperitoneal injections of NAC on postnatal days 7–17. After 35 days, both eyes of all rats were processed for histology. Some sections were stained with hematoxylin and eosin to assess structural changes and other sections were immunostained to determine the location of IGF-1. Frozen sections also were prepared and stained for adenosine triphosphatase to detect retinal blood vessels. Compared to the controls, more blood vessels, many of which were abnormal, and increased IGF-1 expression were observed in group 2. In group 3, abnormal blood vessels and IGF-1 expression were less evident. NAC appeared to be an effective vascular-protective agent for ROP by decreasing IGF-1 expression.     

Isolation and characterization of a sea urchin hsp 70 gene segment

Three clones containing Paracentrotus lividus sea urchin DNA sequences which cross-hybridize to Drosophila heat shock protein (hsp) 70 gene were isolated. The sequence arrangements in the three cloned DNA inserts were compared by restriction and cross-hybridization analysis. The results showed that they contain four different genes related to one Drosophila hsp 70 gene. One of these genes was subcloned, and two of the isolated fragments were shown to hybridize to genomic DNA and to RNA from heat-treated sea urchin embryo.