Unique Sensitivity of Uterine Tissue and the Immune System for Endometriotic Lesion Formation.

Endometriosis is a debilitating disease that affects about 10% of reproductive-aged adolescents and women. The etiology of the disease is unknown; however, a prevailing hypothesis is that endometriosis develops from retrograde menstruation, where endometrial tissue and fluids flow back through the oviducts into the peritoneal cavity. There is no cure for endometriosis, and symptoms are treated palliatively.

NCI Alliance for Nanotechnology in Cancer - from academic research to clinical interventions.

The National Cancer Institute (NCI) of National Institutes of Health has funded and operated the NCI Alliance for Nanotechnology in Cancer - a large multi-disciplinary program which leverages research at the intersection of molecular biology, oncology, physics, chemistry, and engineering to develop innovative cancer interventions. The program has demonstrated that convergence of several scientific disciplines catalyzes innovation and progress in cancer nanotechnology and advances its clinical translation. This paper takes a look at last thirteen years of the Alliance program operations and delineates its outcomes, successes, and outlook for the future.

Comparing Surfactant Penetration into Human Skin and Resulting Skin Dryness Using and Methods.

Numerous tests have been developed to estimate a surfactant's mildness in rinse-off formulations. In this study, mixed surfactant systems were examined for their impact on surfactant penetration into the skin and skin hydration using and methods. A forearm controlled application test (FCAT) was conducted, and skin hydration was evaluated using corneometry and visual dryness grading.

Conventional and pioneer modes of glucocorticoid receptor interaction with enhancer chromatin in vivo.

Glucocorticoid hormone plays a major role in metabolism and disease. The hormone-bound glucocorticoid receptor (GR) binds to a specific set of enhancers in different cell types, resulting in unique patterns of gene expression. We have addressed the role of chromatin structure in GR binding by mapping nucleosome positions in mouse adenocarcinoma cells.

Cell-to-cell communication in cancer: workshop report.

Recent advances in cancer biology and the development of new research tools have enabled interrogations of single cells and cell-cell interactions. Emerging technologies are capable of revealing data on the physical characteristics of cells, differences in the genome and proteome between cancerous and healthy cells, and variations in distinct cell subpopulations. Dynamic measurements enable studies that can reveal the evolution of cell characteristics.

Nanocuration workflows: Establishing best practices for identifying, inputting, and sharing data to inform decisions on nanomaterials.

There is a critical opportunity in the field of nanoscience to compare and integrate information across diverse fields of study through informatics (i.e., nanoinformatics).

Experiences in supporting the structured collection of cancer nanotechnology data using caNanoLab.

The cancer Nanotechnology Laboratory (caNanoLab) data portal is an online nanomaterial database that allows users to submit and retrieve information on well-characterized nanomaterials, including composition, in vitro and in vivo experimental characterizations, experimental protocols, and related publications. Initiated in 2006, caNanoLab serves as an established resource with an infrastructure supporting the structured collection of nanotechnology data to address the needs of the cancer biomedical and nanotechnology communities. The portal contains over 1,000 curated nanomaterial data records that are publicly accessible for review, comparison, and re-use, with the ultimate goal of accelerating the translation of nanotechnology-based cancer therapeutics, diagnostics, and imaging agents to the clinic.

Nanotechnologies in cancer treatment and diagnosis.

Despite significant efforts toward research and treatment development, cancer continues to be a major health problem in the United States that is only further enhanced by the heterogeneous nature of the disease. Nanotechnology has evolved as a technology with applications to medicine and the potential to improve clinical outcomes, with its application to cancer garnering much attention recently. In particular, through the generation of novel nanoscale devices and therapeutic platforms, nanotechnologies have emerged as innovative approaches that enable the detection and diagnosis of cancer at its earliest stages, and the delivery of anticancer drugs directly to tumors.

NCI investment in nanotechnology: achievements and challenges for the future.

Nanotechnology offers an exceptional and unique opportunity for developing a new generation of tools addressing persistent challenges to progress in cancer research and clinical care. The National Cancer Institute (NCI) recognizes this potential, which is why it invests roughly $150 M per year in nanobiotechnology training, research and development. By exploiting the various capacities of nanomaterials, the range of nanoscale vectors and probes potentially available suggests much is possible for precisely investigating, manipulating, and targeting the mechanisms of cancer across the full spectrum of research and clinical care.

caNanoLab: data sharing to expedite the use of nanotechnology in biomedicine.

The use of nanotechnology in biomedicine involves the engineering of nanomaterials to act as therapeutic carriers, targeting agents and diagnostic imaging devices. The application of nanotechnology in cancer aims to transform early detection, targeted therapeutics and cancer prevention and control. To assist in expediting and validating the use of nanomaterials in biomedicine, the National Cancer Institute (NCI) Center for Biomedical Informatics and Information Technology, in collaboration with the NCI Alliance for Nanotechnology in Cancer (Alliance), has developed a data sharing portal called caNanoLab.

Overlapping chromatin-remodeling systems collaborate genome wide at dynamic chromatin transitions.

ATP-dependent chromatin remodeling is an essential process required for the dynamic organization of chromatin structure. Here we describe the genome-wide location and activity of three remodeler proteins with diverse physiological functions in the mouse genome: Brg1, Chd4 and Snf2h. The localization patterns of all three proteins substantially overlap with one another and with regions of accessible chromatin.

Ectopic hippocampal neurogenesis in adolescent male rats following alcohol dependence.

The adolescent hippocampus is highly vulnerable to alcohol-induced damage, which could contribute to their increased susceptibility to alcohol use disorder. Altered adult hippocampal neurogenesis represents one potential mechanism by which alcohol (ethanol) affects hippocampal function. Based on the vulnerability of the adolescent hippocampus to alcohol-induced damage, and prior reports of long-term alcohol-induced effects on adult neurogenesis, we predicted adverse effects on adult neurogenesis in the adolescent brain following abstinence from alcohol dependence.

Complex genomic interactions in the dynamic regulation of transcription by the glucocorticoid receptor.

The glucocorticoid receptor regulates transcriptional output through complex interactions with the genome. These events require continuous remodeling of chromatin, interactions of the glucocorticoid receptor with chaperones and other accessory factors, and recycling of the receptor by the proteasome. Therefore, the cohort of factors expressed in a particular cell type can determine the physiological outcome upon treatment with glucocorticoid hormones.

Adolescent binge alcohol exposure alters hippocampal progenitor cell proliferation in rats: effects on cell cycle kinetics.

Binge alcohol exposure in adolescent rats potently inhibits adult hippocampal neurogenesis by altering neural progenitor cell (NPC) proliferation and survival; however, it is not clear whether alcohol results in an increase or decrease in net proliferation. Thus, the effects of alcohol on hippocampal NPC cell cycle phase distribution and kinetics were assessed in an adolescent rat model of an alcohol use disorder. Cell cycle distribution was measured using a combination of markers (Ki-67, bromodeoxyuridine incorporation, and phosphohistone H3) to determine the proportion of NPCs within G1, S, and G2/M phases of the cell cycle.

Adolescent binge alcohol exposure induces long-lasting partial activation of microglia.

Accumulating evidence indicates that the adolescent hippocampus is highly susceptible to alcohol-induced structural damage and behavioral deficits. Microglia are vitally important brain constituents needed to support and maintain proper neural function; however, alcohol's effects on microglia have only recently gained attention. The microglial response to alcohol during adolescence has yet to be studied; therefore, we examined hippocampal microglial activation in an adolescence binge alcohol exposure model.

Roles of neural stem cells and adult neurogenesis in adolescent alcohol use disorders.

This review discusses the contributions of a newly considered form of plasticity, the ongoing production of new neurons from neural stem cells, or adult neurogenesis, within the context of neuropathologies that occur with excessive alcohol intake in the adolescents. Neural stem cells and adult neurogenesis are now thought to contribute to the structural integrity of the hippocampus, a limbic system region involved in learning, memory, behavioral control, and mood. In adolescents with alcohol use disorders (AUDs), the hippocampus appears to be particularly vulnerable to the neurodegenerative effects of alcohol, but the role of neural stem cells and adult neurogenesis in alcoholic neuropathology has only recently been considered.

Alcohol inhibition of neurogenesis: a mechanism of hippocampal neurodegeneration in an adolescent alcohol abuse model.

Adolescents diagnosed with an alcohol use disorder show neurodegeneration in the hippocampus, a region important for learning, memory, and mood regulation. This study examines a potential mechanism by which excessive alcohol intake, characteristic of an alcohol use disorder, produces neurodegeneration. As hippocampal neural stem cells underlie ongoing neurogenesis, a phenomenon that contributes to hippocampal structure and function, we investigated aspects of cell death and cell birth in an adolescent rat model of an alcohol use disorder.

Organismal differences in post-translational modifications in histones H3 and H4.

Post-translational modifications (PTMs) of histones play an important role in many cellular processes, notably gene regulation. Using a combination of mass spectrometric and immunobiochemical approaches, we show that the PTM profile of histone H3 differs significantly among the various model organisms examined. Unicellular eukaryotes, such as Saccharomyces cerevisiae (yeast) and Tetrahymena thermophila (Tet), for example, contain more activation than silencing marks as compared with mammalian cells (mouse and human), which are generally enriched in PTMs more often associated with gene silencing.

Identification of histone H3 lysine 36 acetylation as a highly conserved histone modification.

Histone lysine acetylation is a major mechanism by which cells regulate the structure and function of chromatin, and new sites of acetylation continue to be discovered. Here we identify and characterize histone H3K36 acetylation (H3K36ac). By mass spectrometric analyses of H3 purified from Tetrahymena thermophila and Saccharomyces cerevisiae (yeast), we find that H3K36 can be acetylated or methylated.

Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex.

The yeast histone deacetylase Rpd3 can be recruited to promoters to repress transcription initiation. Biochemical, genetic, and gene-expression analyses show that Rpd3 exists in two distinct complexes. The smaller complex, Rpd3C(S), shares Sin3 and Ume1 with Rpd3C(L) but contains the unique subunits Rco1 and Eaf3.

Methylation of histone H3 lysine 36 is required for normal development in Neurospora crassa.

The SET domain is an evolutionarily conserved domain found predominantly in histone methyltransferases (HMTs). The Neurospora crassa genome includes nine SET domain genes (set-1 through set-9) in addition to dim-5, which encodes a histone H3 lysine 9 HMT required for DNA methylation. We demonstrate that Neurospora set-2 encodes a histone H3 lysine 36 (K36) methyltransferase and that it is essential for normal growth and development.

Histone H3 K36 methylation is associated with transcription elongation in Schizosaccharomyces pombe.

Set2 methylation of histone H3 at lysine 36 (K36) has recently been shown to be associated with RNA polymerase II (Pol II) elongation in Saccharomyces cerevisiae. However, whether this modification is conserved and associated with transcription elongation in other organisms is not known. Here we report the identification and characterization of the Set2 ortholog responsible for K36 methylation in the fission yeast Schizosaccharomyces pombe.