The Mi-2 Homolog Mit1 Actively Positions Nucleosomes Within Heterochromatin to Suppress Transcription

Eukaryotic DNA is packaged into the nucleus in complex with proteins that regulate access and utilization of the genetic material. These DNA and protein complexes form a dynamic structure known as chromatin. Nucleosomes are the repeating unit of chromatin, and consist of DNA wrapped around an octamer of histone proteins. Nucleosomes can then be modified and spatially arranged to facilitate processes such as transcription, DNA replication, and repair. A special transcriptionally repressive chromatin structure assembles onto gene-poor, repetitive regions of the genome known as constitutive heterochromatin. Mit1 is the putative chromatin remodeling subunit of the fission yeast Snf2/HDAC repressor complex (SHREC) and is known to repress transcription at regions of heterochromatin. However, how Mit1 modifies chromatin to silence transcription is largely unknown. Here we report that Mit1 mobilizes histone octamers in vitro Document Type: Doctoral Dissertation Name: Kevin M. Creamer Email Address: [email protected] Title: The Mi-2 Homolog Mit1 Actively Positions Nucleosomes within Heterochromatin to Suppress Transcription Degree: Doctor of Philosophy Program (Major): Biomedical Sciences Concentration (Track): Cell Biology and Biochemistry Research Advisor: Janet F. Partridge, Ph.D. Advisor\u27s Email: [email protected] Committee Members: Mark Bix, Ph.D. Paul K. Brindle, Ph.D. Linda M. Hendershot, Ph.D. Ronald N. Laribee, Ph.D. Keywords: chromatin remodeling, fission yeast, heterochromatin, Mit1, SHREC Availability: Embargoed for 12 months Graduation Date: May 2014 and requires ATP hydrolysis and conserved chromatin tethering domains including a previously unrecognized chromodomain to remodel nucleosomes and silence transcription. Loss of Mit1 remodeling activity results in nucleosome depletion at specific DNA sequences that display low intrinsic affinity for the histone octamer, but its contribution to antagonizing RNA Polymerase II access and transcription is not restricted to these sites. Genetic epistasis analyses demonstrate that SHREC subunits and the transcription coupled Set2 histone methyltransferase, which is involved in suppression of cryptic transcription at actively transcribed regions, cooperate to silence heterochromatic transcripts. In addition, we demonstrate that Mit1’s remodeling activity contributes to SHREC function independently of Clr3’s histone deacetylase activity on Lys14 of histone H3. We propose that chromatin remodeling by Mit1 cooperates with the Clr3 and other chromatin modifiers to stabilize heterochromatin structure and to prevent access to the transcriptional machinery

A note on the Hybrid Soil Moisture Deficit Model v2.0

peer-reviewedThe Hybrid Soil Moisture Deficit (HSMD) model has been used for a wide range of applications, including modelling of grassland productivity and utilisation, assessment of agricultural management opportunities such as slurry spreading, predicting nutrient emissions to the environment and risks of pathogen transfer to water. In the decade since its publication, various ad hoc modifications have been developed and the recent publication of the Irish Soil Information System has facilitated improved assessment of the spatial soil moisture dynamics. In this short note, we formally present a new version of the model (HSMD2.0), which includes two new soil drainage classes, as well as an optional module to account for the topographic wetness index at any location. In addition, we present a new Indicative Soil Drainage Map for Ireland, based on the Irish Soil Classification system, developed as part of the Irish Soil Information System

Post-traumatic stress disorder: findings from the Australian National Survey of Mental Health and Well-being

Background. We report on the epidemiology of post-traumatic stress disorder (PTSD) in the Australian community, including information on lifetime exposure to trauma, 12-month prevalence of PTSD, sociodemographic correlates and co-morbidity. Methods. Data were obtained from a stratified sample of 10641 participants as part of the Australian National Survey of Mental Health and Well-being. A modified version of the Composite International Diagnostic Interview was used to determine the presence of PTSD, as well as other DSM-IV anxiety, affective and substance use disorders. Results. The estimated 12-month prevalence of PTSD was 1.33%, which is considerably lower than that found in comparable North American studies. Although females were at greater risk than males within the subsample of those who had experienced trauma, the large gender differences noted in some recent epidemiological research were not replicated. Prevalence was elevated among the never married and previously married respondents, and was lower among those aged over 55. For both men and women, rape and sexual molestation were the traumatic events most likely to be associated with PTSD. A high level of Axis 1 co-morbidity was found among those persons with PTSD Conclusions. PTSD is a highly prevalent disorder in the Australian community and is routinely associated with high rates of anxiety, depression and substance disorders. Future research is needed to investigate rates among other populations outside the North American continent.M. Creamer, P. Burgess and A. C. Mcfarlan

Scoping biological indicators of soil quality Phase II. Defra Final Contract Report SP0534

This report presents results from a field assessment of a limited suite of potential biological indicators of soil quality to investigate their suitability for national-scale soil monitoring

Recent advances in the analysis of therapeutic proteins by capillary and microchip electrophoresis

The development of therapeutic proteins and peptides is an expensive and time-intensive process. Biologics, which have become a multi-billion dollar industry, are chemically complex products that require constant observation during each stage of development and production. Post-translational modifications along with chemical and physical degradation from oxidation, deamidation, and aggregation, lead to high levels of heterogeneity that affect drug quality and efficacy. The various separation modes of capillary electrophoresis (CE) are commonly utilized to perform quality control and assess protein heterogeneity. This review attempts to highlight the most recent developments and applications of CE separation techniques for the characterization of protein and peptide therapeutics by focusing on papers accepted for publication in the in the two-year period between January 2012 and December 2013. The separation principles and technological advances of CE, capillary gel electrophoresis, capillary isoelectric focusing, capillary electrochromatography and CE-mass spectrometry are discussed, along with exciting new applications of these techniques to relevant pharmaceutical issues. Also included is a small selection of papers on microchip electrophoresis to show the direction this field is moving with regards to the development of inexpensive and portable analysis systems for on-site, high-throughput analysis

Headache in an HIV positive patient: diagnostic challenges and approach to treatment

Headaches are a common complaint in HIV positive patients attending emergency services. A thorough understanding of the differential diagnoses, initial investigations and empirical management of this presentation is essential for the assessing physician. We discuss a case of a patient with known advanced HIV infection presenting with headache to the emergency department. Given the range of possible diagnoses, broad-spectrum antimicrobial therapy was initially commenced. This was stopped when magnetic resonance imaging confirmed a diagnosis of venous sinus thrombosis. Anticoagulation therapy was started in accordance with current clinical guidelines after discussing the rationale and options for treatment with the patient. Here, we review the guidelines and supporting evidence for management of venous sinus thrombosis, and consider the challenges and strategies for engaging a patient with previous poor attendance in their ongoing care

CD1d expression demarcates CDX4+ hemogenic mesoderm with definitive hematopoietic potential

To achieve efficient, reproducible differentiation of human pluripotent stem cells (hPSCs) towards specific hematopoietic cell-types, a comprehensive understanding of the necessary cell signaling and developmental trajectories involved is required. Previous studies have identified the mesodermal progenitors of extra-embryonic-like and intra-embryonic-like hemogenic endothelium (HE), via stage-specific WNT and ACTIVIN/NODAL, with GYPA/GYPB (CD235a/b) expression serving as a positive selection marker for mesoderm harboring exclusively extra-embryonic-like hemogenic potential. However, a positive mesodermal cell-surface marker with exclusively intra-embryonic-like hemogenic potential has not been identified. Recently, we reported that early mesodermal expression of CDX4 critically regulates definitive HE specification, suggesting that CDX4 may act in a cell-autonomous manner during hematopoietic development. To identify CDX4+ mesoderm, we performed single cell (sc)RNAseq on hPSC-derived mesodermal cultures, revealing CDX