Hardisonaagaard0687

Chromatin organizes DNA and regulates its transcriptional activity through epigenetic modifications. Heterochromatic regions of the genome are generally transcriptionally silent, while euchromatin is more prone to transcription. During DNA replication, both genetic information and chromatin modifications must be faithfully passed on to daughter strands. There is evidence that DNA polymerases play a role in transcriptional silencing, but the extent of their contribution and how it relates to heterochromatin maintenance is unclear.

We isolate a strong hypomorphic Arabidopsis thaliana mutant of the POL2A catalytic subunit of DNA polymerase epsilon and show that POL2A is required to stabilize heterochromatin silencing genome-wide, likely by preventing replicative stress. We reveal that POL2A inhibits DNA methylation and histone H3 lysine 9 methylation. Hence, the release of heterochromatin silencing in POL2A-deficient mutants paradoxically occurs in a chromatin context of increased levels of these two repressive epigenetic marks. At the nuclear level, the POL2A defect is associated with fragmentation of heterochromatin.

These results indicate that POL2A is critical to heterochromatin structure and function, and that unhindered replisome progression is required for the faithful propagation of DNA methylation throughout the cell cycle.

These results indicate that POL2A is critical to heterochromatin structure and function, and that unhindered replisome progression is required for the faithful propagation of DNA methylation throughout the cell cycle.

The relationship between adipocyte fatty acid-binding protein (AFABP) and cardiac remodelling has been reported in cross-sectional studies, although with conflicting results. Type 2 diabetes mellitus (T2DM) is associated with left ventricular (LV) hypertrophy and diastolic dysfunction, as well as elevated circulating AFABP levels. Here we investigated prospectively the association between AFABP with the longitudinal changes of cardiac remodelling and diastolic dysfunction in T2DM.

Circulating AFABP levels were measured in 176 T2DM patients without cardiovascular diseases (CVD) at baseline. All participants received detailed transthoracic echocardiography both at baseline and after 1year. Multivariable linear and Cox regression analyses were used to evaluate the associations of circulating AFABP levels with changes in echocardiography parameters and incident major adverse cardiovascular events (MACE), respectively.

The median duration between baseline and follow-up echocardiography assessments was 28months. Higher sex-specific AFABP quartiles at baseline were associated with increase in LV mass and worsening of average E/e' (all P < 0.01). Multivariable linear regression demonstrated that AFABP in the highest quartile was independently associated with both increase in LV mass (β = 0.89, P < 0.01) and worsening of average E/e' (β = 0.57, P < 0.05). Moreover, multivariable Cox regression analysis showed that elevated baseline circulating AFABP level independently predicted incident MACE (HR 2.65, 95% CI 1.16-6.05, P < 0.05) after adjustments for age, sex, body mass index, glycated haemoglobin, hypertension, dyslipidemia and presence of chronic kidney disease.

Circulating AFABP level at baseline predicted the development of LV hypertrophy, diastolic dysfunction and MACE in T2DM patients without CVD.

Circulating AFABP level at baseline predicted the development of LV hypertrophy, diastolic dysfunction and MACE in T2DM patients without CVD.

The E6 oncoproteins of human papillomavirus (HPV) 16/18 are the critical drivers of cervical cancer (CC) progression. Extracellular vesicles (EVs) are emerging as critical mediators of cancer-tumor microenvironment (TME) communication. However, whether EVs contribute to HPV 16/18 E6-mediated impacts on CC progression remains unclear.

A series of in vitro and in vivo assays were performed to elucidate the roles and mechanism of EV-Wnt7b in HPV E6-induced CC angiogenesis. click here The prognostic value of serum EV-Wnt7b was determined and a predictive nomogram model was established.

HPV 16/18 E6 upregulated Wnt7b mRNA expression in four HPV 16/18-positive CC cell lines and their EVs. In vitro and in vivo experiments demonstrated that EV-Wnt7b mRNA was transferred to and modulated human umbilical vein endothelial cells (HUVECs) toward more proliferative and proangiogenic behaviors by impacting β-catenin signaling. Clinically, serum EV-Wnt7b levels were elevated in CC patients and significantly correlated with an aggressive phenotype. Serum EV-Wnt7b was determined to be an independent prognostic factor for CC overall survival (OS) and recurrence-free survival (RFS). Notably, we successfully established a novel predictive nomogram model using serum EV-Wnt7b, which showed good prediction of 1- and 3-year OS and RFS.

Our results illustrate a potential crosstalk between HPV 16/18-positive CC cells and HUVECs via EVs in the TME and highlight the potential of circulating EV-Wnt7b as a novel predictive biomarker for CC prognosis.

Our results illustrate a potential crosstalk between HPV 16/18-positive CC cells and HUVECs via EVs in the TME and highlight the potential of circulating EV-Wnt7b as a novel predictive biomarker for CC prognosis.

Sexual risk behaviours that occur among young men are based on dominant notions and practices that prevail in cultural contexts. As such, understanding the intersection of cultural norms and sexual risk behaviours among young men is very important.

The study used a qualitative design and conducted four focus group discussions with 36 male students who were purposively selected from different levels of study at the University of KwaZulu-Natal. Data were analysed through line-by-line coding, and grouped into emerging themes and sub-themes facilitated by the use of Atlas.ti.

The findings emphasize that socialisation agents such as the family, peers and community play an important role in prescribing acceptable and unacceptable sexual behaviour of young men. Some of the young men seemed to adhere to prescribed gender norms of what it means to be a man while some rejected them for alternative versions of being a man. In the context of the university environment, these findings reveal that male students cannot make informed decisions regarding condom use when they are intoxicated, and thus expose themselves to sexually transmitted infections and other risks.