Transition from Transient DNA Rereplication to Inherited Gene Amplification Following Prolonged Environmental Stress.

Cells require the ability to adapt to changing environmental conditions, however, it is unclear how these changes elicit stable permanent changes in genomes. We demonstrate that, in response to environmental metal exposure, the metallothionein (MT) locus undergoes DNA rereplication generating transient site-specific gene amplifications (TSSGs). Chronic metal exposure allows transition from MT TSSG to inherited MT gene amplification through homologous recombination within and outside of the MT locus.

Isolation and analysis of rereplicated DNA by Rerep-Seq.

Changes in gene copy number contribute to genomic instability, the onset and progression of cancer, developmental abnormalities and adaptive potential. The origins of gene amplifications have remained elusive; however, DNA rereplication has been implicated as a source of gene amplifications. The inability to determine which sequences are rereplicated and under what conditions have made it difficult to determine the validity of the proposed models.

The conserved and divergent roles of Prdm3 and Prdm16 in zebrafish and mouse craniofacial development.

The formation of the craniofacial skeleton is a highly dynamic process that requires proper orchestration of various cellular processes in cranial neural crest cell (cNCC) development, including cell migration, proliferation, differentiation, polarity and cell death. Alterations that occur during cNCC development result in congenital birth defects and craniofacial abnormalities such as cleft lip with or without cleft palate. While the gene regulatory networks facilitating neural crest development have been extensively studied, the epigenetic mechanisms by which these pathways are activated or repressed in a temporal and spatially regulated manner remain largely unknown.

Epigenetic Modulation of the Tumor Immune Microenvironment to Potentiate Immune Checkpoint Blockade Therapy.

Response rates to immune checkpoint blockade (ICB) in KRAS-mutant lung adenocarcinoma remain poor. In this issue of , Li and colleagues report an CRISPR screen of epigenetic regulators of the tumor immune microenvironment that uncovers as a tumor-intrinsic suppressor of ICB through suppression of GM-CSF expression..

Preclinical evaluation of (99m)Tc labeled chondroitin sulfate for monitoring of cartilage degeneration in osteoarthritis.

Purpose: In previous in-vitro and ex-vivo studies we proved the specific uptake of (99m)Tc radiolabeled chondroitin sulfate (CS) in human articular cartilage. As a logical next step for the clinical use for imaging osteoarthritis we investigated in-vivo uptake of (99m)TcCS in dogs.

Procedures: The radiolabeling of CS Condrosulf (IBSA, Lugano, Switzerland) was performed using 25mg of CS and 20-40MBq/kg body weight of (99m)Tc by means of the tin method.

The anaphase promoting complex regulates yeast lifespan and rDNA stability by targeting Fob1 for degradation.

Genomic stability, stress response, and nutrient signaling all play critical, evolutionarily conserved roles in lifespan determination. However, the molecular mechanisms coordinating these processes with longevity remain unresolved. Here we investigate the involvement of the yeast anaphase promoting complex (APC) in longevity.

Uptake studies with chondrotropic 99mTc-chondroitin sulfate in articular cartilage. Implications for imaging osteoarthritis in the knee.

Chondroitin sulfate (CS) is an endogenous component of extracellular matrix in the cartilage and can be valuable for imaging of cartilage degeneration after radiolabeling. Data monitoring the uptake of (99m)TcCS by human cartilage are rare. Radiolabeling was performed by (99m)TcO4(-)/tin method at pH5.

Antagonistic Gcn5-Hda1 interactions revealed by mutations to the Anaphase Promoting Complex in yeast.

Background: Histone post-translational modifications are critical for gene expression and cell viability. A broad spectrum of histone lysine residues have been identified in yeast that are targeted by a variety of modifying enzymes. However, the regulation and interaction of these enzymes remains relatively uncharacterized.

Optimal 99mTc radiolabeling and uptake of glucosamine sulfate by cartilage. A potential tracer for scintigraphic detection of osteoarthritis.

Glucosamine sulfate (GS) is used in treatment of human osteoarthritis, but no data for(99m)TcGS scintigraphy are available. Radiolabeling of GS was performed using the (99m)TcO(4)(-)/tin method. We applied two procedures for separation of free (99m)Tc using PD10 and G10 columns.

Uptake of 99mTc-labeled chondroitin sulfate by chondrocytes and cartilage: a promising agent for imaging of cartilage degeneration?

Chondroitin sulfate (CS) is used in the treatment of human osteoarthritis as a slow-acting symptomatic drug. For this reason, we performed uptake studies with (99m)TcCS using different chondrocyte cultures, as well as cartilage tissue in vitro. For uptake studies, adherent monolayer cultures of human chondrocytes (2.