The Reverse Transcription Inhibitor Abacavir Shows Anticancer Activity in Prostate Cancer Cell Lines

Background: Transposable Elements (TEs) comprise nearly 45% of the entire genome and are part of sophisticated regulatory network systems that control developmental processes in normal and pathological conditions. The retroviral/ retrotransposon gene machinery consists mainly of Long Interspersed Nuclear Elements (LINEs-1) and Human Endogenous Retroviruses (HERVs) that code for their own endogenous reverse transcriptase (RT). Interestingly, RT is typically expressed at high levels in cancer cells. Recent studies report that RT inhibition by non-nucleoside reverse transcriptase inhibitors (NNRTIs) induces growth arrest and cell differentiation in vitro and antagonizes growth of human tumors in animal model. In the present study we analyze the anticancer activity of Abacavir (ABC), a nucleoside reverse transcription inhibitor (NRTI), on PC3 and LNCaP prostate cancer cell lines. Principal Findings: ABC significantly reduces cell growth, migration and invasion processes, considerably slows S phase progression, induces senescence and cell death in prostate cancer cells. Consistent with these observations, microarray analysis on PC3 cells shows that ABC induces specific and dose-dependent changes in gene expression, involving multiple cellular pathways. Notably, by quantitative Real-Time PCR we found that LINE-1 ORF1 and ORF2 mRNA levels were significantly up-regulated by ABC treatment. Conclusions: Our results demonstrate the potential of ABC as anticancer agent able to induce antiproliferative activity and trigger senescence in prostate cancer cells. Noteworthy, we show that ABC elicits up-regulation of LINE-1 expression, suggesting the involvement of these elements in the observed cellular modifications

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Spitzer Microlensing Parallax for OGLE-2017-BLG-0896 Reveals a Counter-rotating Low-mass Brown Dwarf

The kinematics of isolated brown dwarfs in the Galaxy, beyond the solar neighborhood, is virtually unknown. Microlensing has the potential to probe this hidden population, as it can measure both the mass and five of the six phase-space coordinates (all except the radial velocity) even of a dark isolated lens. However, the measurements of both the microlens-parallax and finite-source effects are needed in order to recover the full information. Here, we combine the Spitzer satellite parallax measurement with the ground-based light curve, which exhibits strong finite-source effects, of event OGLE-2017-BLG-0896. We find two degenerate solutions for the lens (due to the known satellite-parallax degeneracy), which are consistent with each other except for their proper motion. The lens is an isolated brown dwarf with a mass of either 18 ± 1 M J or 20 ± 1 M J . This is the lowest isolated-object mass measurement to date, only ~45% more massive than the theoretical deuterium-fusion boundary at solar metallicity, which is the common definition of a free-floating planet. The brown dwarf is located at either 3.9 ± 0.1 kpc or 4.1 ± 0.1 kpc toward the Galactic bulge, but with proper motion in the opposite direction of disk stars, with one solution suggesting it is moving within the Galactic plane. While it is possibly a halo brown dwarf, it might also represent a different, unknown population

Epigenetic mechanisms and associated brain circuits in the regulation of positive emotions: A role for transposable elements.

Epigenetic programming and reprogramming are at the heart of cellular differentiation and represent developmental and evolutionary mechanisms in both germline and somatic cell lines. Only about 2% of our genome is composed of protein-coding genes, while the remaining 98%, once considered "junk" DNA, codes for regulatory/epigenetic elements that control how genes are expressed in different tissues and across time from conception to death. While we already know that epigenetic mechanisms are at play in cancer development and in regulating metabolism (cellular and whole body), the role of epigenetics in the developing prenatal and postnatal brain, and in maintaining a proper brain activity throughout the various stages of life, in addition to having played a critical role in human evolution, is a relatively new domain of knowledge. Here we present the current state-of-the-art techniques and results of these studies within the domain of emotions, and then speculate on how genomic and epigenetic mechanisms can modify and potentially alter our emotional (limbic) brain and affect our social interactions. J. Comp. Neurol. 524:2944-2954, 2016. © 2016 Wiley Periodicals, Inc

In silico analysis of mobile elements-derived sequences in schizophrenia-related genes

BackgroundRegulation of Transposable Elements (TEs) expression has already been associated with complex human diseases, in particular cancer [1]. Also, complex diseases cannot be explained only by genetic factors and are likely to be the result of gene-environment interactions with the contribution of TEs. The detection of retroviral transcripts in the brains of schizophrenics suggests that activation or upregulation of distinct human endogenous retroviruses (HERVs) may play a role in the etiopatho-genesis of neuropsychiatric diseases [2], with increasing complications if we consider that TE insertions generate somatic mosaicism in neuronal cells [3]. In addition, mobile elements have been heavily involved in tissue-specific promoter activity [4] that makes them good candidates for brain specific activation of genes related to schizophrenia. Eventually, TEs are thought to be important in regulation of methylation and DNA accessibility to transcription factors [5]. They are also an important source of small RNAs, which usually act to silence TEs [6]; a particular family of small RNAs, miRNAs, has already been shown to alter neural receptors' function [7]

Violence against Women and Stress-Related Disorders: Seeking for Associated Epigenetic Signatures, a Pilot Study

Background: Violence against women is a relevant health and social problem with negative consequences on women’s health. The interaction between genome and environmental factors, such as violence, represents one of the major challenges in molecular medicine. The Epigenetics for WomEn (EpiWE) project is a multidisciplinary pilot study that intends to investigate the epigenetic signatures associated with intimate partner and sexual violence-induced stress-related disorders. Materials and Methods: In 2020, 62 women exposed to violence (13 women suffering from sexual violence and 49 from Intimate Partner Violence, IPV) and 50 women with no history of violence were recruited at the Service for Sexual and Domestic Violence. All women aged 18–65 were monitored for their physical and psychological conditions. Blood samples were collected, and DNAs were extracted and underwent the epigenetic analysis of 10 stress-related genes. Results: PTSD prevalence in victims was assessed at 8.1%. Quantitative methylation evaluation of the ten selected trauma/stress-related genes revealed the differential iper-methylation of brain-derived neurotrophic factor, dopamine receptor D2 and insulin-like growth factor 2 genes. These genes are among those related to brain plasticity, learning, and memory pathways. Conclusions: The association of early detection of posttraumatic distress and epigenetic marker identification could represent a new avenue for addressing women survivors toward resilience. This innovative approach in gender-based violence studies could identify new molecular pathways associated with the long-term effects of violence and implement innovative protocols of precision medicine

Clinical features and assessments obtained using the ADI-R, ADOS, CARS and PEP-3 diagnostic scales.

̂<p>ne: not evaluated.</p>*<p>ASS: Autism Severity Score.</p>1<p>: Communication;</p>2<p>: Motor;</p>3<p>: Maladaptative behaviors.</p