The Tetraspanins CD9 and CD81 Regulate CD9P1-Induced Effects on Cell Migration

CD9P-1 is a cell surface protein with immunoglobulin domains and an unknown function that specifically associates with tetraspanins CD9 and CD81. Overexpression of CD9P-1 in HEK-293 cells induces dramatic changes in cell spreading and migration on various matrices. Experiments using time-lapse videomicroscopy revealed that CD9P-1 expression has led to higher cell motility on collagen I but lower motility on fibronectin through a β1-integrins dependent mechanism. On collagen I, the increase in cell motility induced by CD9P-1 expression was found to involve integrin α2β1 and CD9P-1 was observed to associate with this collagen receptor. The generation of CD9P-1 mutants demonstrated that the transmembrane and the cytoplasmic domains are necessary for inducing effects on cell motility. On the other hand, expression of tetraspanins CD9 or CD81 was shown to reverse the effects of CD9P-1 on cell motility on collagen I or fibronectin with a concomitant association with CD9P-1. Thus, the ratio of expression levels between CD9P-1 and its tetraspanin partners can regulate cell motility

Tetraspanin CD151 is a novel prognostic marker in poor outcome endometrial cancer

BACKGROUND: Type II cancers account for 10% of endometrial cancers but 50% of recurrence. Response rates to chemotherapy at recurrence are poor and better prognostic markers are needed to guide therapy. CD151 is a small transmembrane protein that regulates cell migration and facilitates cancer metastasis. High CD151 expression confers poor prognosis in breast, pancreatic and colorectal cancer. The prognostic significance of tetraspanin CD151 expression in poor outcome endometrial cancers was evaluated, along with oestrogen receptor (ER), progesterone receptor (PR), p53, human epidermal growth factor receptor -2 (HER-2), and CD 151 staining compared with α6β1, α3β1 integrins, and E-cadherin. METHODS: Tissue microarray constructed from 156 poor outcome endometrial cancers, tested with immunohistochemistry and staining correlated with clinicopathological data were used. A total of 131 data sets were complete for analysis. RESULTS: Expression of CD151 was significantly higher in uterine papillary serous and clear cell carcinoma than in grade 3 endometrioid carcinoma, sarcoma or carcinosarcoma (P<0.001). In univariate analysis, age, stage, histology type and CD151 were significant for both recurrence free (RFS) and disease specific survival (DSS). In multivariate analyses, CD151 was significant for RFS and DSS (P=0.036 and 0.033, respectively) in triple negative (ER, PR and HER-2 negative) tumours (88/131). The HER-2, p53, ER and PR were not prognostic for survival. There was strong concordance of CD151 with E-cadherin (98%), but not with α6β1 (35%), α3β1 staining (60%). CONCLUSION: The CD151 is a novel marker in type 2 cancers that can guide therapeutic decisions. CD151 may have an important role in tumourigenesis in some histology types

Escape from Autologous Neutralizing Antibodies in Acute/Early Subtype C HIV-1 Infection Requires Multiple Pathways

One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can limit replication of genetically diverse viruses and prevent establishment of a new infection. Thus, identifying the strengths and weaknesses of Nab during the early stages of natural infection could prove useful in achieving this goal. Here we demonstrate that viral escape readily occurred despite the development of high titer autologous Nab in two subjects with acute/early subtype C infection. To provide a detailed portrayal of the escape pathways, Nab resistant variants identified at multiple time points were used to create a series of envelope (Env) glycoprotein chimeras and mutants within the background of a corresponding newly transmitted Env. In one subject, Nab escape was driven predominantly by changes in the region of gp120 that extends from the beginning of the V3 domain to the end of the V5 domain (V3V5). However, Nab escape pathways in this subject oscillated and at times required cooperation between V1V2 and the gp41 ectodomain. In the second subject, escape was driven by changes in V1V2. This V1V2-dependent escape pathway was retained over time, and its utility was reflected in the virus's ability to escape from two distinct monoclonal antibodies (Mabs) derived from this same patient via introduction of a single potential N-linked glycosylation site in V2. Spatial representation of the sequence changes in gp120 suggested that selective pressure acted upon the same regions of Env in these two subjects, even though the Env domains that drove escape were different. Together the findings argue that a single mutational pathway is not sufficient to confer escape in early subtype C HIV-1 infection, and support a model in which multiple strategies, including potential glycan shifts, direct alteration of an epitope sequence, and cooperative Env domain conformational masking, are used to evade neutralization

Genetic instability and anti-HPV immune response as drivers of infertility associated with HPV infection

Funding Information: RFBR grant 17–54-30002, Ministry of Science and Higher Education of the Russian Federation (Agreement No. 075–15–2019-1660) to Olga Smirnova. Publisher Copyright: © 2021, The Author(s).Human papillomavirus (HPV) is a sexually transmitted infection common among men and women of reproductive age worldwide. HPV viruses are associated with epithelial lesions and cancers. HPV infections have been shown to be significantly associated with many adverse effects in reproductive function. Infection with HPVs, specifically of high-oncogenic risk types (HR HPVs), affects different stages of human reproduction, resulting in a series of adverse outcomes: 1) reduction of male fertility (male infertility), characterized by qualitative and quantitative semen alterations; 2) impairment of couple fertility with increase of blastocyst apoptosis and reduction of endometrial implantation of trophoblastic cells; 3) defects of embryos and fetal development, with increase of spontaneous abortion and spontaneous preterm birth. The actual molecular mechanism(s) by which HPV infection is involved remain unclear. HPV-associated infertility as Janus, has two faces: one reflecting anti-HPV immunity, and the other, direct pathogenic effects of HPVs, specifically, of HR HPVs on the infected/HPV-replicating cells. Adverse effects observed for HR HPVs differ depending on the genotype of infecting virus, reflecting differential response of the host immune system as well as functional differences between HPVs and their individual proteins/antigens, including their ability to induce genetic instability/DNA damage. Review summarizes HPV involvement in all reproductive stages, evaluate the adverse role(s) played by HPVs, and identifies mechanisms of viral pathogenicity, common as well as specific for each stage of the reproduction process.publishersversionPeer reviewe

Lattice distortion in a zircon population and its effects on trace element mobility and U-Th-Pb isotope systematics: examples from the Lewisian Gneiss Complex, Northwest Scotland

Zircon is a key mineral in geochemical and geochronological studies in a range of geological settings as it is mechanically and chemically robust. However, distortion of its crystal lattice can facilitate enhanced diffusion of key elements such as U and Pb. Electron backscatter diffraction (EBSD) analysis of ninety-nine zircons from the Lewisian Gneiss Complex (LGC) of northwest Scotland has revealed five zircons with lattice distortion. The distortion can take the form of gradual bending of the lattice or division of the crystal into subgrains. Zircon lattices are distorted because of either post-crystallisation plastic distortion or growth defects. Three of the five distorted zircons, along with many of the undistorted zircons in the population, were analysed by ion microprobe to measure U and Pb isotopes, Ti and REEs. Comparison of Th/U ratio, 207Pb/206Pb age, REE profile and Ti concentration between zircons with and without lattice distortion suggests that the distortion is variably affecting the concentration of these trace elements and isotopes within single crystals, within samples and between localities. REE patterns vary heterogeneously, sometimes relatively depleted in heavy REEs or lacking a Eu anomaly. Ti-in-zircon thermometry records temperatures that were either low (~700 °C) or high (>900 °C) relative to undistorted zircons. One distorted zircon records apparent 207Pb/206Pb isotopic ages (−3.0 to +0.3 % discordance) in the range of ~2,420–2,450 Ma but this does not correlate with any previously dated tectonothermal event in the LGC. Two other distorted zircons give discordant ages of 2,331 ± 22 and 2,266 ± 40 Ma, defining a discordia lower intercept within error of a late amphibolite-facies tectonothermal event. This illustrates that Pb may be mobilised in distorted zircons at lower metamorphic grade than in undistorted zircons. These differences in trace element abundances and isotope systematics in distorted zircons relative to undistorted zircons are generally interpreted to have been facilitated by subgrain walls. Trace elements and isotopes would have moved from undistorted lattice into these subgrain walls as their chemical potential is modified due to the presence of the dislocations which make up the subgrain wall. Subgrain walls provided pathways for chemical exchange between crystal and surroundings. Only five per cent of zircons in this population have lattice distortion suggesting it will not have a major impact on zircon geochronology studies, particularly as three of the five distorted zircons are from strongly deformed rocks not normally sampled in such studies. However, this does suggest there may be a case for EBSD analysis of zircons prior to geochemical analysis when zircons from highly deformed rocks are to be investigated

Insatisfação com a imagem corporal e relação com estado nutricional, adiposidade corporal e sintomas de anorexia e bulimia em adolescentes Body image dissatisfaction and its relationship with nutritional status, body fat, and anorexia and bulimia symptoms in adolescents

Objetivos: Identificar a prevalência de insatisfação com a imagem corporal e de sintomas de anorexia e bulimia em adolescentes do sexo feminino da cidade de Santa Maria (RS) e verificar a associação da insatisfação com a imagem corporal com estado nutricional, adiposidade corporal e sintomas de anorexia e bulimia. Método: Foram analisadas 258 adolescentes do sexo feminino (11 a 13 anos), estudantes de escolas públicas. Aplicou-se o Body Shape Questionnaire e o Teste de Atitudes Alimentares (EAT-26). Foram calculados o índice de massa corporal e o percentual de gordura. Foram utilizados o teste qui-quadrado e a regressão logística. Resultados: A prevalência de insatisfação com a imagem corporal foi de 25,3% e a de sintomas de anorexia e bulimia foi de 27,6%. A insatisfação com a imagem corporal apresentou associação com o estado nutricional, sendo que as adolescentes com excesso de peso apresentaram maior insatisfação (razão de chances = 2,64; IC95%= 1,02-6,83). Conclusão: As prevalências de insatisfação corporal e sintomas de anorexia e bulimia foram elevadas. O estado nutricional parece ser o melhor preditor da insatisfação corporal.<br>Objectives: To identify the prevalence of body image dissatisfaction and anorexia and bulimia symptoms in adolescent girls from the city of Santa Maria, Brazil, and to determine the association of body image dissatisfaction with nutritional status, body fat, and anorexia and bulimia symptoms. Method: We investigated 258 adolescent girls (11 to 13 years) from public schools. The Body Shape Questionnaire and the Eating Attitudes Test (EAT-26) were used. Body mass index and percent body fat were calculated. The chi-square test and logistic regression were used. Results: The prevalence of body image dissatisfaction was 25.3% and the prevalence of anorexia and bulimia symptoms was 27.6%. Body image dissatisfaction was associated with nutritional status, with overweight girls presenting higher dissatisfaction (OR = 2.64; 95%CI 1.02-6.83). Conclusion: The prevalence rates of body image dissatisfaction and anorexia and bulimia symptoms were high. Nutritional status seems to be a better predictor of body image dissatisfaction

Influência de fatores socioeconômicos, comportamentais e nutricionais na insatisfação com a imagem corporal de universitárias em Florianópolis, SC Influence of socioeconomic, behavioral and nutritional factors on dissatisfaction with body image among female university students in Florianopolis, SC

Este estudo objetivou estimar a prevalência de insatisfação com a imagem corporal e testar a associação com fatores socioeconômicos, comportamentais e nutricionais em universitárias ingressantes de uma universidade pública em Florianópolis, SC. A insatisfação com a imagem corporal foi investigada por meio do Body Shape Questionnaire (BSQ-34), em uma amostra de 220 estudantes. O estado nutricional foi investigado por meio do índice de massa corporal (IMC), circunferência da cintura (CC) e percentual de gordura corporal (%GC). As características socioeconômicas (idade, renda familiar mensal e escolaridade dos pais), bem como consumo energético e prática de regimes para emagrecer também foram investigados. Os fatores associados à insatisfação com a imagem corporal foram testados pela regressão de Poisson. A prevalência de insatisfação com a imagem corporal foi de 47,3% (IC 95% 40,7; 53,9). O estado nutricional segundo IMC e a prática de regimes para emagrecer foram as variáveis que se mostraram associadas à insatisfação corporal. Os resultados apontam indicadores de uma elevada prevalência de rejeição da própria forma física entre as universitárias, o que sinaliza a necessidade de ações nutricionais nas universidades, a fim de esclarecer e prevenir atitudes alimentares anormais entre os estudantes.<br>This study aimed to estimate the prevalence of dissatisfaction with body image and associated socio-economic, behavioral and dietary factors in female university students from a public university in Florianopolis, SC. Body image was assessed by the Body Shape Questionnaire (BSQ-34) in a sample of 220 students. Nutritional status was investigated by body mass index (BMI), waist circumference (WC), and body fat percentage (%BF). Socio-economic characteristics (age, monthly household income, and parental schooling) as well as energy intake and going on restrictive diets were also investigated. Factors associated with dissatisfaction with body image were analyzed by multivariate Poisson regression analysis. The prevalence of dissatisfaction with body image was 47.3% (95% CI 40.7; 53.9). Nutritional status by BMI and going on a diet to lose weight were the variables associated with body dissatisfaction. Results showed a high prevalence of indicators of rejection of their physical fitness among university students, which signals toward the need for nutritional education actions at universities in order to clarify and prevent abnormal eating attitudes among students