Consensus guidelines for the definition, detection and interpretation of immunogenic cell death.

Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation

Unbounded boundaries and shifting baselines: estuaries and coastal seas in a rapidly changing world

This Special Issue of Estuarine, Coastal and Shelf Science presents contributions from ECSA 55; an international symposium organised by the Estuarine and Coastal Sciences Association (ECSA) and Elsevier on the broad theme of estuaries and coastal seas in times of intense change. The objectives of the SI are to synthesise, hypothesise and illustrate the impacts of global change on estuaries and coastal seas through learning lessons from the past, discussing the current and forecasting for the future. It is highlighted here that establishing impacts and assigning cause to the many pressures of global change is and will continue to be a formidable challenge in estuaries and coastal seas, due in part to: (1) their complexity and unbounded nature; (2) difficulties distinguishing between human-induced changes and natural variations and; (3) multiple pressures and effects. The contributing authors have explored a number of these issues over a range of disciplines. The complexity and connectivity of estuaries and coastal seas have been investigated through studies of physicochemical and ecological components, whilst the human imprint on the environment has been identified through a series of predictive, contemporary, historical and palaeo approaches. The impact of human activities has been shown to occur over a range of spatial and temporal scales, requiring the development of integrated management approaches. These 30 articles provide an important contribution to our understanding and assessment of the impacts of global change. The authors highlight methods for essential management/mitigation of the consequences of global change and provide a set of directions, ideas and observations for future work. These include the need to consider: (1) the cumulative, synergistic and antagonistic effects of multiple pressures; (2) the importance of unbounded boundaries and connectivity across the aquatic continuum; (3) the value of combining cross-disciplinary palaeo, contemporary and future modelling studies and; (4) the importance of shifting baselines on ecosystem functioning and the future provision of ecosystem services

UBVRI Light curves of 44 Type Ia supernovae

We present UBVRI photometry of 44 Type la supernovae (SNe la) observed from 1997 to 2001 as part of a continuing monitoring campaign at the Fred Lawrence Whipple Observatory of the Harvard-Smithsonian Center for Astrophysics. The data set comprises 2190 observations and is the largest homogeneously observed and reduced sample of SNe la to date, nearly doubling the number of well-observed, nearby SNe la with published multicolor CCD light curves. The large sample of [U-band photometry is a unique addition, with important connections to SNe la observed at high redshift. The decline rate of SN la U-band light curves correlates well with the decline rate in other bands, as does the U - B color at maximum light. However, the U-band peak magnitudes show an increased dispersion relative to other bands even after accounting for extinction and decline rate, amounting to an additional ∼40% intrinsic scatter compared to the B band

Pre-surgical neoadjuvant oncolytic virotherapy confers protection against rechallenge in a murine model of breast cancer

The use of oncolytic viruses (OVs) for cancer treatment is emerging as a successful strategy that combines the direct, targeted killing of the cancer with the induction of a long-lasting anti-tumor immune response. Using multiple aggressive murine models of triple-negative breast cancer, we have recently demonstrated that the early administration of oncolytic Maraba virus (MRB) prior to surgical resection of the primary tumor is sufficient to minimize the metastatic burden, protect against tumor rechallenge, cure a fraction of the mice and sensitize refractory tumors to immune checkpoint blockade without the need for further treatment. Here, we apply our surgical model to other OVs: Vesicular stomatitis virus (VSV), Adenovirus (Ad), Reovirus (Reo) and Herpes simplex virus (HSV) and show that all of the tested OVs could positively change the outcome of the treated animals. The growth of the primary and secondary tumors was differently affected by the various OVs and most of the viruses conferred survival benefits in this neoadjuvant setting despite the absence of direct treatment following rechallenge. This study establishes that OV-therapy confers long-term protection when administered in the pre-operative window of opportunity.Therapeutic cell differentiatio

Supplementary Material for: Interferon-Dependent Induction of Clr-b during Mouse Cytomegalovirus Infection Protects Bystander Cells from Natural Killer Cells via NKR-P1B-Mediated Inhibition

Natural killer (NK) cells are innate lymphocytes that aid in self-nonself discrimination by recognizing cells undergoing pathological alterations. The NKR-P1B inhibitory receptor recognizes Clr-b, a self-encoded marker of cell health downregulated during viral infection. Here, we show that Clr-b loss during mouse cytomegalovirus (MCMV) infection is predicated by a loss of Clr-b (<i>Clec2d</i>) promoter activity and nascent transcripts, driven in part by MCMV <i>ie3</i> (M122) activity. In contrast, uninfected bystander cells near MCMV-infected fibroblasts reciprocally upregulate Clr-b expression due to paracrine type-I interferon (IFN) signaling. Exposure of fibroblasts to type-I IFN augments <i>Clec2d</i> promoter activity and nascent Clr-b transcripts, dependent upon a cluster of IRF3/7/9 motifs located ∼200 bp upstream of the transcriptional start site. Cells deficient in type-I IFN signaling components revealed IRF9 and STAT1 as key transcription factors involved in Clr-b upregulation. In chromatin immunoprecipitation experiments, the <i>Clec2d</i> IRF cluster recruited STAT2 upon IFN-α exposure, confirming the involvement of ISGF3 (IRF9/STAT1/STAT2) in positively regulating the <i>Clec2d</i> promoter. These findings demonstrate that Clr-b is an IFN-stimulated gene on healthy bystander cells, in addition to a missing-self marker on MCMV-infected cells, and thereby enhances the dynamic range of innate self-nonself discrimination by NK cells