The American Bombardment of Kampuchea, 1969-1973

On the American bombing of Cambodia during the Vietnam War

Microprocessor, Setx, Xrn2, and Rrp6 Co-operate to Induce Premature Termination of Transcription by RNAPII

SummaryTranscription elongation is increasingly recognized as an important mechanism of gene regulation. Here, we show that microprocessor controls gene expression in an RNAi-independent manner. Microprocessor orchestrates the recruitment of termination factors Setx and Xrn2, and the 3′–5′ exoribonuclease, Rrp6, to initiate RNAPII pausing and premature termination at the HIV-1 promoter through cleavage of the stem-loop RNA, TAR. Rrp6 further processes the cleavage product, which generates a small RNA that is required to mediate potent transcriptional repression and chromatin remodeling at the HIV-1 promoter. Using chromatin immunoprecipitation coupled to high-throughput sequencing (ChIP-seq), we identified cellular gene targets whose transcription is modulated by microprocessor. Our study reveals RNAPII pausing and premature termination mediated by the co-operative activity of ribonucleases, Drosha/Dgcr8, Xrn2, and Rrp6, as a regulatory mechanism of RNAPII-dependent transcription elongation

Multicenter evaluation of parametric response mapping as an indicator of bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156134/2/ajt15814_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156134/1/ajt15814.pd

Moth Project: Four Deadlines & a Dinner/TALKCPR Bevan Commission Annual Conference 2017/18

Four Deadlines & a Dinner was a MOTH collaborative practice project working with 20 Stage 2 Graphic Design students at Falmouth University along with external partners from medicine, palliative care, writing, design for the live environment and VR. During this four week period, students worked across a range of death & design projects, they discussed and delivered ideas and potential solutions relating to end of life experiences. With Dr Mark Taubert Clinical Director/Consultant in Palliative Medicine at Velindre NHS Trust, Cardiff, we explored how visual communication designers and medics could benefit from sharing knowledge and skills to impact on policy and practice with regard to end of life matters, in particular with patients with life limiting illness and their choices regarding DNACPR. The work produced from this will exhibited at the Bevan Commission Health and Social Welfare Conference in Wales in September 2017. In collaboration with Ben James, Creative Director at Jotta Design and Anna Kiernan a Senior Lecturer in Writing, we considered our own personal eulogies and innovative ways in which to store our digital selves as either a digital legacy or digital archive beyond our physical life. MOTH hosted a Death Over Dinner party, where our guests were invited to eat and engage in meaningful conversations and questions about the end-of-life, we also held a film night where we screened AfterLife, by Hirokazu Kore-eda: Newly deceased find themselves in a way station somewhere between Heaven and Earth. With the help of caseworkers, each soul is given three days to choose one memory from their life that they will relive for eternity. The project also included a tour of artist’s graves at Falmouth Cemetery run by Glyn Winchester from Falmouth Art Gallery. + Bevan Commission Annual Conference 2017.Swansea Wales. The Bevan Commission is an independent and authoritative think tank made up of international experts who help challenge current NHS thinking and practice to ensure it is fit for the future. It provides its advice to Welsh Government on all matters relating to health, the NHS and social care in Wales.Chaired by Professor Sir Mansel Aylward CB. With Dr Mark Taubert MOTH explored how visual communication designers and medics could benefit from sharing knowledge and skills to impact on policy and practice with regard to end of life matters, in particular with patients with life limiting illness and their choices regarding DNACPR. + NHS talkcpr.wales The MOTH Talk CPR Art in Medicine Project. Talk CPR – Discuss DNACPR Talk CPR’s goal is to encourage conversation about CardioPulmonary Resuscitation (CPR) for people affected by life-limiting and palliative illnesses. Talking about Do Not Attempt CardioPulmonary Resuscitation (DNACPR) is an important part of advance care planning and can help minimise distress at a later stage. + NICE National Institute for Health and Care Excellence. Shared Learning database. The MOTH TalkCPR Art in Medicine Project. The MOTH TalkCPR Art in Medicine Project., January 2018. This submission sets out the journey we took to consider whether graphic design in medical palliative care settings could be a powerful and effective way of addressing practical, psychological, social and spiritual issues that face people at the end of their lives. The 'Talk CPR' project in Wales has multiple facets, including work in 2017 with graphic design lecturers and students from Falmouth University, who have their own End-of-life project called MOTH. This is an 'ethnographical' approach to research, more details of which can be found here. The project lead met art school lecturers and students to describe the issue of resuscitation in palliative settings and tasked them with creating visual and graphic stimuli to encourage frank discussion about future wishes surrounding death, dying and matters such as wishes around cardiopulmonary resuscitation. This resulted in the students creating thought-provoking artwork that looked at dying from a very different angle, compared to the more typical mainstream healthcare approaches of blue background patient information leaflets. Students produced videos, images and photographs. Aims and objectives Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) discussions and forms are nearly always initiated by doctors, and they can be a source of distress, harm and complaints from patients and their loved-ones. In 2015, a national campaign in Wales called 'Sharing and Involving- TalkCPR', sought to put patients at the centre of discussions. As part of this endeavour, the TalkCPR project group led by Dr Mark Taubert, met with the Falmouth University Moth group, to discuss graphic design initiatives for patients to trigger patient led discussions on DNACPR. The brief was for the artwork to bring about reflection and encourage individuals to ask the question: "Would I actually want CPR in the last years of my life?" Furthermore, in line with NICE Guidelines for End of Life Care in adults (QS13), NG31 and NG61 for end of life care for children, infants and young people with life limiting conditions, it sought to encourage patients and healthcare professionals to approach the advance care planning topic without too much trepidation, and without fear of upsetting the person they were talking to. Key learning points Further exhibitions in hospitals are planned for 2018 and 2019. The designs and posters have been used in medical students and junior doctor teaching sessions in Velindre Cancer Centre and in Llandough hospital. One of the Moth/TalkCPR videos has been disseminated via Youtube link on Twitter and has received very positive feedback. Graphic design is everywhere around us, casting its influence and shaping our thoughts and views. But those working in healthcare or experiencing illness often do not have the opportunity to change or influence this art. The Moth/TalkCPR project sought to change this shortfall, whilst also acknowledging that it is difficult to ‘measure the impact of art’, given how each of us perceives and processes such things very differently. The relationship between medicine, death and graphic design helped shape this project and we wanted to explore how art and graphic design can be used to promote and forward NICE guidance on end-of-life care, including the often used advice that we need to talk more about our dying moments

Expression of Neurog1 Instead of Atoh1 Can Partially Rescue Organ of Corti Cell Survival

In the mammalian inner ear neurosensory cell fate depends on three closely related transcription factors, Atoh1 for hair cells and Neurog1 and Neurod1 for neurons. We have previously shown that neuronal cell fate can be altered towards hair cell fate by eliminating Neurod1 mediated repression of Atoh1 expression in neurons. To test whether a similar plasticity is present in hair cell fate commitment, we have generated a knockin (KI) mouse line (Atoh1KINeurog1) in which Atoh1 is replaced by Neurog1. Expression of Neurog1 under Atoh1 promoter control alters the cellular gene expression pattern, differentiation and survival of hair cell precursors in both heterozygous (Atoh1+/KINeurog1) and homozygous (Atoh1KINeurog1/KINeurog1) KI mice. Homozygous KI mice develop patches of organ of Corti precursor cells that express Neurog1, Neurod1, several prosensory genes and neurotrophins. In addition, these patches of cells receive afferent and efferent processes. Some cells among these patches form multiple microvilli but no stereocilia. Importantly, Neurog1 expressing mutants differ from Atoh1 null mutants, as they have intermittent formation of organ of Corti-like patches, opposed to a complete ‘flat epithelium’ in the absence of Atoh1. In heterozygous KI mice co-expression of Atoh1 and Neurog1 results in change in fate and patterning of some hair cells and supporting cells in addition to the abnormal hair cell polarity in the later stages of development. This differs from haploinsufficiency of Atoh1 (Pax2cre; Atoh1f/+), indicating the effect of Neurog1 expression in developing hair cells. Our data suggest that Atoh1KINeurog1 can provide some degree of functional support for survival of organ of Corti cells. In contrast to the previously demonstrated fate plasticity of neurons to differentiate as hair cells, hair cell precursors can be maintained for a limited time by Neurog1 but do not transdifferentiate as neurons

A Rapid and Highly Sensitive Method of Non Radioactive Colorimetric In Situ Hybridization for the Detection of mRNA on Tissue Sections

Background: Non Radioactive colorimetric In Situ Hybridization (NoRISH) with hapten labeled probes has been widely used for the study of gene expression in development, homeostasis and disease. However, improvement in the sensitivity of the method is still needed to allow for the analysis of genes expressed at low levels. Methodology/Principal Findings: A stable, non-toxic, zinc-based fixative was tested in NoRISH experiments on sections of mouse embryos using four probes (Lhx6, Lhx7, ncapg and ret) that have different spatial patterns and expression levels. We showed that Z7 can successfully replace paraformaldehyde used so far for tissue fixation in NoRISH; the morphology of the cryosections of Z7-fixed tissues was excellent, and the fixation time required for tissues sized 1 cm was 1 hr instead of 24 hr for paraformaldehyde. The hybridization signal on the sections of the Z7-treated embryos always appeared earlier than that of the PFA-fixed embryos. In addition, a 50–60 % shorter detection time was observed in specimen of Z7-treated embryos, reducing significantly the time required to complete the method. Finally and most importantly, the strength of the hybridization signal on the sections of the Z7-treated embryos always compared favorably to that of the sections of PFAfixed embryos; these data demonstrate a significant improvement of the sensitivity the method that allows for the analysis of mRNAs that are barely or not detected by the standard colorimetric NoRISH method. Conclusions/Significance: Our NoRISH method provides excellent preservation of tissue morphology, is rapid, highl