Editorial: Coastal risk: shores and deltas in peril

Coastal systems are the result of a natural equilibrium between hydrodynamic, atmospheric, and terrestrial parameters and sediment dynamics. In the Anthropocene, this equilibrium in many coastal regions can be altered by human activities. These activities may globally magnify the effects of extreme meteorological events and sea level rise and directly influence coastal processes down to a local scale within and between river catchments, the sea, and the coast. While most interventions, such as urban development, seawalls, and jetties are placed for specific human benefits, their indirect effects on coastal economies, societies and ecosystems can be significant. [...

Beach morphodynamic classification using high-resolution nearshore bathymetry and process-based wave modelling

Classification of beach morphodynamic state relies on accurate representation of breaking wave conditions, Hb (plus grain size and spring tidal range). Measured breaking wave data, however, are absent from all but a handful of sites worldwide. Here, we apply process-based wave modelling for propagating offshore waves to the breaking zone using high-resolution nearshore bathymetry, obtaining representative and accurate Hb values for multiple beaches at regional scale, and thereby derive meaningful morphodynamic classifications that accord with observed beach state. Ninety-five beaches on the north coast of Ireland were investigated, with observed beach types and states compared to predictions based on morphodynamic parameters determined using wave, tide and sediment data, obtained from field surveys and detailed numerical wave modelling. The coast is exposed to micro-through meso-tides (0.43–3.90 m) and low sea through high swell waves (Hb = 0.13–1.18 m) and is composed of fine to medium sand resulting in a full range of beach types (wave-dominated, tide-modified and tide-dominated) and most beach states, thereby providing a comprehensive field laboratory to undertake such a comparison. We found that modal beach types reside within their predicted Relative Tide Range (RTR) and modal beach states close to the predicted dimensionless fall velocity (Ω) range. The use of high-resolution nearshore wave modelling to determine Hb was deemed the most appropriate approach for deriving predicted beach classification. The work follows the investigation of the same coast by Jackson et al. (2005) who found shortcomings in relating beach types to breaker wave conditions. However, advances in inshore wave modelling and access to high-resolution nearshore bathymetry since then have enabled improved estimates of breaker height, producing more accurate results and enhancing previous work. The results highlight the need to obtain accurate estimates of Hb and Tp if they are to be used effectively in predicting beach parameters. This work therefore sets a precedence for other coastal sites worldwide where detailed nearshore bathymetry is available and Hb can be derived from process-based wave modelling, improving the classification and prediction of morphodynamic beach type and state

Coastal shoreline change assessments at global scales

During the present era of rapid climate change and sea-level rise, coastal change science is needed at global, regional, and local scales. Essential elements of this science, regardless of scale, include that the methods are defendable and that the results are independently verifiable. The recent contribution by Almar et al.1 does not achieve either of these measures as shown by: (i) the use of an error-prone proxy for coastal shoreline and (ii) analyses that are circular and explain little of the data variance

Multifactorial Origins of Heart and Gut Defects in nipbl-Deficient Zebrafish, a Model of Cornelia de Lange Syndrome

nipbl-deficient zebrafish provide evidence that heart and gut defects in Cornelia de Lange Syndrome are caused by combined effects of multiple gene expression changes that occur during early embryonic development

Suppression of Lung Adenocarcinoma Progression by Nkx2-1

Despite the high prevalence and poor outcome of patients with metastatic lung cancer the mechanisms of tumour progression and metastasis remain largely uncharacterized. Here we modelled human lung adenocarcinoma, which frequently harbours activating point mutations in KRAS and inactivation of the p53 pathway, using conditional alleles in mice. Lentiviral-mediated somatic activation of oncogenic Kras and deletion of p53 in the lung epithelial cells of Kras[superscript LSL-G12D/+];p53[superscript flox/flox] mice initiates lung adenocarcinoma development4. Although tumours are initiated synchronously by defined genetic alterations, only a subset becomes malignant, indicating that disease progression requires additional alterations. Identification of the lentiviral integration sites allowed us to distinguish metastatic from non-metastatic tumours and determine the gene expression alterations that distinguish these tumour types. Cross-species analysis identified the NK2-related homeobox transcription factor Nkx2-1 (also called Ttf-1 or Titf1) as a candidate suppressor of malignant progression. In this mouse model, Nkx2-1 negativity is pathognomonic of high-grade poorly differentiated tumours. Gain- and loss-of-function experiments in cells derived from metastatic and non-metastatic tumours demonstrated that Nkx2-1 controls tumour differentiation and limitsmetastatic potential in vivo. Interrogation of Nkx2-1-regulated genes, analysis of tumours at defined developmental stages, and functional complementation experiments indicate that Nkx2-1 constrains tumours in part by repressing the embryonically restricted chromatin regulator Hmga2. Whereas focal amplification of NKX2-1 in a fraction of human lung adenocarcinomas has focused attention on its oncogenic function, our data specifically link Nkx2-1 downregulation to loss of differentiation, enhanced tumour seeding ability and increased metastatic proclivity. Thus, the oncogenic and suppressive functions ofNkx2-1 in the sametumourNational Institutes of Health (U.S.) (grant U01-CA84306 )National Institutes of Health (U.S.) (grant K99-CA151968)Howard Hughes Medical InstituteLudwig Center for Molecular OncologyNational Cancer Institute (U.S.) (Cancer Center Support (core) grant P30-CA14051

Tracking SARS-CoV-2 mutations and variants through the COG-UK-Mutation Explorer.

COG-UK Mutation Explorer (COG-UK-ME, https://sars2.cvr.gla.ac.uk/cog-uk/-last accessed date 16 March 2022) is a web resource that displays knowledge and analyses on SARS-CoV-2 virus genome mutations and variants circulating in the UK, with a focus on the observed amino acid replacements that have an antigenic role in the context of the human humoral and cellular immune response. This analysis is based on more than 2 million genome sequences (as of March 2022) for UK SARS-CoV-2 data held in the CLIMB-COVID centralised data environment. COG-UK-ME curates these data and displays analyses that are cross-referenced to experimental data collated from the primary literature. The aim is to track mutations of immunological importance that are accumulating in current variants of concern and variants of interest that could alter the neutralising activity of monoclonal antibodies (mAbs), convalescent sera, and vaccines. Changes in epitopes recognised by T cells, including those where reduced T cell binding has been demonstrated, are reported. Mutations that have been shown to confer SARS-CoV-2 resistance to antiviral drugs are also included. Using visualisation tools, COG-UK-ME also allows users to identify the emergence of variants carrying mutations that could decrease the neutralising activity of both mAbs present in therapeutic cocktails, e.g. Ronapreve. COG-UK-ME tracks changes in the frequency of combinations of mutations and brings together the curated literature on the impact of those mutations on various functional aspects of the virus and therapeutics. Given the unpredictable nature of SARS-CoV-2 as exemplified by yet another variant of concern, Omicron, continued surveillance of SARS-CoV-2 remains imperative to monitor virus evolution linked to the efficacy of therapeutics