Identifying and characterising young, nearby, low-mass members of stellar moving groups

Since the early 1990s, several groups of comoving, coeval stars younger than 100Myr and within 100 pc have been revealed. Studying and identifying members in these ‘Nearby Young Moving Groups’ (MGs) is vital because they provide: well characterised samples to test pre-main sequence evolution; ideal targets for direct imaging of exoplanets, discs and brown dwarfs; observational evidence for the birthsites of stars in the Solar neighbourhood. Spectroscopy is used to perform tests of membership for 24 M-dwarf candidates of both the Beta Pictoris MG (BPMG) and AB Doradus MG, confirming 8 and 6 new members, respectively. Measurements of lithium provide a precise age for BPMG, using the ‘Lithium Depletion Boundary’ (LDB) technique. This represents the most accurate age yet determined for this important MG and is about double what has been commonly assumed in the literature from other methods. A kinematically unbiased sample of 146 X-ray emitting FGK stars in the Northern hemisphere with short rotation periods chosen from the SuperWASP All-Sky Survey were spectroscopically investigated to assess their ages and kinematics. The search identified 26 stars younger than 200Myr based on their photospheric lithium. Whilst most of these were not associated with any MG, seven are comoving with the sparse (mostly Southern) Octans-Near MG. Infrared photometry is used to identify debris discs amongst M-dwarfs in MGs and their debris disc fractions are compared as a function of mass and age. Eight percent of the sample younger than 40Myr were identified as debris disc objects, although some may have remained undetected because the sensitivity limits for detecting debris discs around M-dwarfs is lower than for higher-mass stars. No debris discs were observed in MGs older than 40Myr, suggesting the timescale for disc removal is more rapid than for higher-mass stars

The role of immunogenic cell death in oncolytic herpes simplex virus-1 infection of cancer cells

Patients living with many cancers, including ovarian cancer (OC), often suffer from a lack of adequate treatment options. In the case of OC, primary debulking surgery followed by platinum and paclitaxel chemotherapy has led to a vast improvement in patient survival over the past few decades, however, rates of drug-resistant recurrence remain high. Research into new, experimental treatment options is therefore warranted for OC and other cancers. Oncolytic viruses (OVs) are replication-competent viruses that can selectively infect and destroy cancerous cell types, while leaving healthy cells unharmed. OVs do this by exploiting differences between cancer and normal cell phenotypes. Herpes simplex virus (HSV)-1, strain 1716 is one example of this type of virus that has shown selectivity for cancer cells in previous preclinical studies, as well as high levels of safety in humans. One prominent area of current OV study seeks to investigate the ability of OVs to induce immunogenic cell death (ICD) – this term describes multiple modes of programmed death pathways that culminate in release of proimmunogenic factors, which facilitate a modification of the host immune system. Two of the most prominent of these pathways are necroptosis and immunogenic apoptosis (IA). Here, I show that while many OV cell lines express the necessary components for necroptosis, they are unable to undergo classical necroptotic death (induced by TSZ). Despite this, HSV-1716 can infect and kill a range of OC lines successfully. I showed that HSV-1716-induced cell death displays two markers of IA yet does not seem to rely solely on apoptosis to kill cells. In addition, it appears not to rely on any components of the necrosome in order to kill cells, even in cells that are competent to typical necroptosis. However, when RIPK3 is overexpressed in HeLa cells, virus-induced cell death increases, as do markers of both necroptosis and IA. To investigate the role of ICP6 in HSV-1716-induced ICD, viral and cell mutants were made possessing various forms of the protein. Full-length ICP6 protein expressed in cell lines had the effect of blocking cellular response to TSZ, but constructs lacking a region known as the RHIM did not. A functionally similar mutation was produced within the RHIM of live HSV-1716 using CRISPR/Cas9 technology, which was shown to have the effect of disrupting ICP6/RIPK3 binding – thought to be the determinant of necroptotic cell death. Despite this, no changes in cell death signalling could be determined between the viruses at all. Interestingly, when cells were infected in combination with TNF-α, or TNF-α in addition to SMAC mimetic, the RHIM-modified virus produced significantly more death than HSV-1716. This suggests that while loss of RIPK3 inhibition is not sufficient to lead to increased necrosis alone, cells infected with this virus are more sensitive to further necrosis induction. This finding may prove to have great utility for producing the next generation of oncolytic viral therapeutics which can induce greater levels of proimmunogenic cell death. From this we can conclude that HSV-1716 is capable of inducing IA in OC cells. Death is not dependent on necroptosis, however additional RIPK3 seems to sensitise cells to death by other means. Cellular binding of viral ICP6 and RIPK3 can be disrupted by modification of the RHIM, although this change has no bearing on ICD signalling alone but can sensitise cells to TNF-α-induced death

Portraying the hosts: Stellar science from planet searches

Information on the full session can be found on this website: https://sites.google.com/site/portrayingthehostscs18/We present a compendium of the splinter session on stellar science from planet searches that was organized as part of the Cool Stars 18 conference. Seven speakers discussed techniques to infer stellar information from radial velocity, transit and microlensing data, as well as new instrumentation and missions designed for planet searches that will provide useful for the study of the cool stars

Synthesis and antiviral properties of spirocyclic [1,2,3]-triazolooxazine nucleosides

An efficient synthesis of spirocyclic triazolooxazine nucleosides is described. This was achieved by the conversion of β-D-psicofuranose to the corresponding azido-derivative, followed by alkylation of the primary alcohol with a range of propargyl bromides - obtained via Sonogashira chemistry. The products of these reactions underwent 1,3-dipolar addition smoothly to generate the protected spirocyclic adducts. These were easily deprotected to give the corresponding ribose nucleosides. The library of compounds obtained was investigated for its antiviral activity, using MHV (Mouse Hepatitis Virus) as a model wherein derivative 3f showed the most promising activity and tolerability

Synthesis and antiviral activity of novel spirocyclic nucleosides

The synthesis of a number of spirocyclic ribonucleosides containing either a triazolic or azetidinic system is described, along with two analogous phosphonate derivatives of the former. These systems were constructed from the same β-D-psicofuranose starting material. The triazole spirocyclic nucleosides were constructed using the 1-azido-1-hydroxymethyl derived sugars, where the primary alcohol was alkylated with a range of propargyl bromides, whereas the azetidine systems orginated from the corresponding 1-cyano-1-hydroxymethyl sugars. Owing to their close similarity with ribavirin, the library of compounds were investigated for their antiviral properties using MHV (Murine Hepatitis Virus) as a model

Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Marrow Transplantation

In 1997, the first consensus guidelines for haematopoietic SCT (HSCT) in autoimmune diseases (ADs) were published, while an international coordinated clinical programme was launched. These guidelines provided broad principles for the field over the following decade and were accompanied by comprehensive data collection in the European Group for Blood and Marrow Transplantation (EBMT) AD Registry. Subsequently, retrospective analyses and prospective phase I/II studies generated evidence to support the feasibility, safety and efficacy of HSCT in several types of severe, treatment-resistant ADs, which became the basis for larger-scale phase II and III studies. In parallel, there has also been an era of immense progress in biological therapy in ADs. The aim of this document is to provide revised and updated guidelines for both the current application and future development of HSCT in ADs in relation to the benefits, risks and health economic considerations of other modern treatments. Patient safety considerations are central to guidance on patient selection and HSCT procedural aspects within appropriately experienced and Joint Accreditation Committee of International Society for Cellular Therapy and EBMT accredited centres. A need for prospective interventional and non-interventional studies, where feasible, along with systematic data reporting, in accordance with EBMT policies and procedures, is emphasized