Regional gene repression by DNA double-strand breaks in G1 phase cells

DNA damage responses (DDR) to double-strand breaks (DSBs) alter cellular transcription programs at the genome-wide level. Through processes that are less well understood, DSBs also alter transcriptional responses locally, which may be important for efficient DSB repair. Here, we developed an approach to elucidate th

Toxoplasma gondii infection drives conversion of NK cells into ILC1-like cells

Innate lymphoid cells (ILCs) were originally classified based on their cytokine profiles, placing natural killer (NK) cells and ILC1s together, but recent studies support their separation into different lineages at steady-state. However, tumors may induce NK cell conversion into ILC1-like cells that are limited to the tumor microenvironment and whether this conversion occurs beyond this environment remains unknown. Here, we describ

Inclusive production in a QCD and N=4 SYM motivated model for soft interactions

The results presented in this paper differ from our previous unsuccessful attempt to predict the rapidity distribution at $W = 7 \,TeV$. The original version of our model (GLMM) only summed a particular class of Pomeron diagrams (enhanced diagrams). We believe that this was the reason for our failure to describe the $7 \,TeV$ inclusive LHC data. We have developed a new approach (GLM) that also includes the summation of the semi-enhanced diagrams.This contribution is essential for a successful description of the inclusive distributions, which is presented here.Comment: 4 pages, 3 figure

Barrier-to-autointegration factor 1 protects against a basal cGAS-STING response

Although the pathogen recognition receptor pathways that activate cell-intrinsic antiviral responses are well delineated, less is known about how the host regulates this response to prevent sustained signaling and possible immune-mediated damage. Using a genome-wide CRISPR-Cas9 screening approach to identify host factors that modulate interferon-stimulated gene (ISG) expression, we identified the DNA binding protein Barrier-to-autointegration factor 1 (Banf1), a previously described inhibitor of retrovirus integration, as a modulator of basal cell-intrinsic immunity. Ablation of Banf1 by gene editing resulted in chromatin activation near host defense genes with associated increased expression of ISGs, includin

DNA double-strand breaks induce H2Ax phosphorylation domains in a contact-dependent manner

Formation of γH2Ax serves as a checkpoint for double-strand break (DSB) repair pathways. Here the authors reveal via integrated chromatin analysis that γH2Ax domains are established by chromosomal contacts with the DSB site

Evaluation of Non-destructive Molecular Diagnostics for the Detection of Neoparamoeba perurans

Peer reviewed paper. Citation: Downes, J. K., Rigby, M. L., Taylor, R. S., Maynard, B. T., MacCarthy, E., O’Connor, I., Marcos-Lopez M., Rodger H. D., Collins E., Ruane N. M. & Cook, M. T. (2017). Evaluation of Non-destructive Molecular Diagnostics for the Detection of Neoparamoeba perurans. Frontiers in Marine Science, 4. https://doi.org/10.3389/fmars.2017.00061 Link: https://www.frontiersin.org/articles/10.3389/fmars.2017.00061/full DOI: https://doi.org/10.3389/fmars.2017.00061 Cited as per the open access policy of Frontiers Media SA.Amoebic gill disease (AGD) caused by Neoparamoeba perurans, has emerged in Europe as a significant problem for the Atlantic salmon farming industry. Gross gill score is the most widely used and practical method for determining AGD severity on farms and informing management decisions on disease mitigation strategies. As molecular diagnosis of AGD remains a high priority for much of the international salmon farming industry, there is a need to evaluate the suitability of currently available molecular assays in conjunction with the most appropriate non-destructive sampling methodology. The aims of this study were to assess a non-destructive sampling methodology (gill swabs) and to compare a range of currently available real-time polymerase chain-reaction (PCR) assays for the detection of N. perurans. Furthermore a comparison of the non-destructive molecular diagnostics with traditional screening methods of gill scoring and histopathology was also undertaken. The study found that all molecular protocols assessed performed well in cases of clinical AGD with high gill scores. A TaqMan based assay (protocol 1) was the optimal assay based on a range of parameters including % positive samples from a field trial performed on fish with gill scores ranging from 0 to 5. A higher proportion of gill swab samples tested positive by all protocols than gill filament biopsies and there was a strong correlation between gill swabs tested by protocol 1 and gross gill score and histology scores. Screening for N. perurans using protocol 1 in conjunction with non-destructive gill swab samples was shown to give the best results

Cerebrospinal fluid neurofilament light concentration predicts brain atrophy and cognition in Alzheimer\u27s disease

Introduction This study assessed the utility of cerebrospinal fluid (CSF) neurofilament light (NfL) in Alzheimer\u27s disease (AD) diagnosis, its association with amyloid and tau pathology, as well as its potential to predict brain atrophy, cognition, and amyloid accumulation. Methods CSF NfL concentration was measured in 221 participants from the Australian Imaging, Biomarkers & Lifestyle Flagship Study of Ageing (AIBL). Results CSF NfL levels as well as NfL/amyloid β (Aβ42) were significantly elevated in AD compared to healthy controls (HC; P \u3c .001), and in mild cognitive impairment (MCI) compared to HC (P = .008 NfL; P\u3c .001 NfL/Aβ42). CSF NfL and NfL/Aβ42 differentiated AD from HC with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.84 and 0.90, respectively. CSF NfL and NfL/Aβ42 predicted cortical amyloid load, brain atrophy, and cognition. Discussion CSF NfL is a biomarker of neurodegeneration, correlating with cognitive impairment and brain neuropathology