The role of D6 in neutrophil migration, melanoma growth and metastasis

Chemokines are members of a family of small structurally related proteins, which can be classified according to the positioning of four conserved cysteine residues, into four families – CC, CXC, CX3C and XC. They have a wide range of functions, from being involved in embryonic development, disease processes and cell migration. Broadly speaking, chemokines can be divided into homeostatic, those that are involved in development, and inflammatory chemokines, which are produced at high levels during infection. In order to exert their function, chemokines bind to seven transmembrane G protein coupled receptors; this causes the activation of numerous different signalling pathways which can lead to cell activation, migration, survival or apoptosis. The chemokine system is further complicated by the existence of a family of atypical receptors. Four of these receptors have been identified to date; CXCR7, CCX-CKR, DARC and D6, and they all share the apparent inability to signal after ligand binding. D6 has been identified as a member of this atypical receptor family with the ability to bind and internalise 12 inflammatory CC chemokines. D6 expression has been demonstrated in barrier tissues, such as the skin, gut and lung, as well as being expressed by numerous leukocyte subsets. Studies looking at the function of D6 have demonstrated its involvement in the resolution phase of inflammation, and D6 may be involved in cell migration and inflammation driven tumourigenesis. Here the analysis of the role of D6 in neutrophil migration has been carried out, in the well-characterised TPA model of skin inflammation. This work also shows that D6 plays a crucial role in melanoma metastasis. In the TPA model of skin inflammation, 129/Bl6 D6KO mice display an exaggerated inflammatory response, which causes the development of a psoriasis-like pathology. This pathology is dependent on T cells and mast cells, and is associated with an alteration in neutrophil positioning. In the inflamed skin of D6KO mice, neutrophils are found at the dermal/epidermal junction, whilst in WT mice, neutrophils are restricted to the dermis. In this model, D6 is required to prevent neutrophils migrating to the dermal/epidermal junction. D6 expression has been demonstrated both in the skin and on neutrophils, so there are two hypotheses to describe how D6 is influencing neutrophil movement in this model. First, D6 on neutrophils is required to limit their migration within the skin, keeping them away from the dermal/epidermal junction, alternatively D6 in the skin may be responsible for chemokine clearance during inflammation, and the localisation of neutrophils is influenced by these chemokines. This work aimed to investigate the role that D6 played on neutrophil localisation in inflamed skin, carried out using a model of neutrophil adoptive transfer. These results demonstrate that expression of D6 by neutrophils does not alter their positioning in inflamed skin, suggesting that the role for D6 in this model is in regulating chemokines within the skin, a hypothesis which requires further investigation. The second part of this work aimed to investigate the role of D6 in melanoma growth and metastasis. D6 has been shown to be involved in murine models of inflammation driven skin tumourigenesis and colon cancer. These data presented here show that D6 does not influence the primary melanoma growth, but has a profound effect on the development of metastases in the lungs, in the murine B16 model. D6 is required for the development of lung metastases, but the precise mechanism is yet unknown. These data suggest that D6 can alter macrophage numbers within the lungs, which permits the development of metastases, as well as pointing towards a role for D6 in lymphangiogenesis within the lungs, which affects metastasis development, perhaps by altering the development of the pre-metastatic niche. Overall, these studies contribute to the investigation of the role of D6 in skin inflammation, and show, for the first time, that D6 is involved in the pulmonary metastasis of melanoma, suggesting D6 may be a potential therapeutic target in pulmonary metastasis

Statistical analysis of SAMBAH survey and associated data

SAMBAH (Static Acoustic Monitoring of the Baltic Sea Harbour Porpoise) was an international project involving all EU countries around the Baltic Sea, funded by those countries and by the EU Life program (Project Number LIFE08 NAT/S/000261). It ran from 1/1/2010 to 30/9/2015. One major goal of the project was to estimate the abundance of Baltic Sea harbour porpoise, by designing and implementing a large-scale multi-year passive acoustic survey. CREEM was contracted to collaborate on the survey design, and provide statistical analysis of resulting data. A number of internal reports were produced and circulated to the project team, detailing aspects of the analysis. In this CREEM technical report, we collate the most recent version of each of these internal reports as a means of making them publicly available.Publisher PD

Loggerhead turtle Caretta caretta density and abundance in Chesapeake Bay and the temperate ocean waters of the southern portion of the Mid-Atlantic Bight

Funding was provided by the NOAA Species Recovery Grants to States program (Award #NA 47200033) issued to the Virginia Department of Game and Inland Fisheries which contracted with the Virginia Aquarium & Marine Science Center Foundation. Additional funding for tags and turtle capture was also provided by US Fleet Forces Command as well as the Virginia Aquarium Batten Collaborative Research Fund and Batten Professional Development Fund.We conducted aerial surveys of sea turtles in 2011 and 2012, incorporating corrections for perception and availability bias in Chesapeake Bay and near-shore continental shelf waters of the Mid-Atlantic Bight off the US states of Virginia and Maryland. Results of these surveys and ancillary research to determine surface times for loggerhead turtles provide us with a new baseline population estimate for turtles in the region. Prior surveys were conducted in Chesapeake Bay in the mid-1980s and early 2000s, and in ocean waters in the late 1970s and early 1980s. Although comparison of density estimates not corrected for availability between prior surveys and this effort suggests that the population of sea turtles, especially loggerhead turtles, is higher than previous estimates, differences between surveys may be the result of survey methodologies and cannot be assumed to be true changes in density. Surface time for availability corrections was calculated using dive summaries from satellite telemetry on 27 loggerhead turtles tracked between 2011 and 2015. We calculated stratified seasonal availability corrections for bay and ocean waters based on assumed differences in turtle behavior and water clarity between the 2 habitats. For each habitat, we provided seasonal corrections for 3 detection depth bins (shallow, moderate, and deep) to account for differences in sub-surface detection ranges. Differences and trends toward differences among availability corrections underscore the need to better understand the many variables that affect surface time for sea turtles in temperate waters, and the effect that availability has on abundance and density estimates.Publisher PDFPeer reviewe

Estimating cetacean density and abundance in the Central and Western Mediterranean Sea through aerial surveys : implications for management

The equipment for data collection was that used during the EU LIFE Nature programme, project LIFE04NAT/GB/000245 project ‘‘Small Cetaceans in the European Atlantic and North Sea (SCANS-II)’’, funded in 2006.Systematic, effective monitoring of animal population parameters underpins successful conservation strategy and wildlife management, but it is often neglected in many regions, including much of the Mediterranean Sea. Nonetheless, a series of systematic multispecies aerial surveys was carried out in the seas around Italy to gather important baseline information on cetacean occurrence, distribution and abundance. The monitored areas included the Pelagos Sanctuary, the Tyrrhenian Sea, portions of the Seas of Corsica and Sardinia, the Ionian Seas as well as the Gulf of Taranto. Overall, approximately 48,000 km were flown in either spring, summer and winter between 2009–2014, covering an area of 444,621 km2. The most commonly observed species were the striped dolphin and the fin whale, with 975 and 83 recorded sightings, respectively. Other sighted cetacean species were the common bottlenose dolphin, the Risso's dolphin, the sperm whale, the pilot whale and the Cuvier's beaked whale. Uncorrected model- and design-based estimates of density and abundance for striped dolphins and fin whales were produced, resulting in a best estimate (model-based) of around 95,000 striped dolphins (CV=11.6%; 95% CI=92,900–120,300) occurring in the Pelagos Sanctuary, Central Tyrrhenian and Western Seas of Corsica and Sardinia combined area in summer 2010. Estimates were also obtained for each individual study region and year. An initial attempt to estimate perception bias for striped dolphins is also provided. The preferred summer 2010 uncorrected best estimate (design-based) for the same areas for fin whales was around 665 (CV=33.1%; 95% CI=350–1,260). Estimates are also provided for the individual study regions and years. The results represent baseline data to develop efficient, long-term, systematic monitoring programmes, essential to evaluate trends, as required by a number of national and international frameworks, and stress the need to ensure that surveys are undertaken regularly and at a sufficient spatial scale. The management implications of the results are discussed also in light of a possible decline of fin whales abundance over the period from the mid-1990s to the present. Further work to understand changes in distribution and to allow for improved spatial models is emphasized.PostprintPeer reviewe

Alumnae Association Bulletin of the School of Nursing, 1972

Alumnae Calendar The President\u27s Message Officers and Chairmen of Committees Financial Report Address by President Herbut School of Nursing Report School of Practical Nursing Report Report by Dr. Mary Louise Soentgen, M.D., F.A.A.P. Report of Patient Services Department Report of Staff Nurses\u27 Association Progress Report of Hospital Activities Scholarship Committee Report - Clerk-Typist Annual Luncheon - Head Table Social Events for 1971-1972 Missing Alumnae Members Jefferson Today Ways and Means Committee Report Constitution and By-Laws Report Sick and Welfare Committee Women\u27s Board Report Baccalaureate Degree Program Luncheon Pictures Resume of Minutes of Alumnae Association Meeting Class News Poem by Rosa Diseroad - 1923 Marriages Births - Hello World In Memoriam Notice

Distribution and Abundance of Fin whales and other baleen whales in the European Atlantic

The abundance of fin whales (Balaenoptera physalus) and other baleen whales was generated from data collected during shipboard sightings surveys as part of the Cetacean Offshore Distribution and Abundance in the European Atlantic project (CODA). The survey area covered offshore waters beyond the continental shelf of the UK, Ireland, France and Spain. The area was stratified into four blocks and was surveyed by five ships during July 2007. Double platform methods employing the trialconfiguration method (BT-method) were used. Fin, sei (B. borealis) and minke whales (B. acutorostrata) were positively identified, with possible sightings of blue whales (B. musculus). Abundance was estimated for these species and for “large baleen whales” which included fin, sei, fin/sei and blue whales. Abundance for the larger species was estimated using the Mark- Recapture Line Transect design-based method and also model-based methods using density surface modelling. Sample size limitations dictated that conventional line transect sampling methods were used to estimate the abundance of minke whales. Estimates from the two methods were comparable but model-based methods improved the precision and were considered best estimates. The density of large baleen whale species was greatest in the southern end of the survey area and water depth, temperature and distance to the 2000m contour were important predictors of their distribution. The total abundance estimated for the entire survey area was 9,019 (CV=0.11) fin whales and 9,619 (CV= 0.11) large baleen whales. The uncertainty around these estimates due to duplicate classification and species identification were explored. The fin whale estimate is likely to be underestimated because it excludes unidentified large whales, of which a large proportion was likely to have been fin whales. Notwithstanding this, these large baleen whale abundance estimates are the first robust estimates (corrected for responsive movement and g(0)) for this area. The estimated abundance of minke whales was 6,765 (CV=0.99) and sightings were restricted to the northern blocks of the survey area. The minke whale estimate, although imprecise and likely underestimated, does provide a baseline figure for this area and, when considered with results from the SCANS-II continental shelf surveys of July 2005, gives a more comprehensive picture of this species in the European Atlantic. These abundance estimates are important contributions to the conservation and management of these species in the Northeast Atlantic

Abundance of baleen whales in the European Atlantic

The abundance of fin whales (Balaenoptera physalus), sei whales (B. borealis) and minke whales (B. acutorostrata) was estimated from data collected during shipboard sightings surveys conducted as part of CODA and TNASS (Faroese block) in July 2007 in offshore waters of the European Atlantic west of the UK, Ireland, France and Spain, combined with data collected from shipboard and aerial surveys of European Atlantic continental shelf waters conducted as part of SCANS-II in July 2005. Double platform methods employing the trial-configuration method (BT-method) were used in all shipboard surveys. Analysis used Mark-Recapture Distance Sampling to account for animals missed on the transect line. Density surface modelling was undertaken to generate model-based abundance estimates and maps of predicted density. Estimates are presented for the SCANS-II and CODA survey areas. Estimates for the Faroese block of TNASS have been presented elsewhere. The abundance of fin whales in the CODA and SCANS-II areas was estimated as 19,354 (CV 0.24) for identified sightings and 29,512 (CV 0.26) when adjusted to include a proportion of unidentified large whale abundance (which included large baleen and sperm whales), prorated by number of sightings, because there were a large number of such sightings in one of the CODA survey blocks. The model-based estimate of identified fin whales was 19,751 (CV 0.17), more precise than the design-based estimate. Fin whales were mainly found in the southern part of the CODA survey area. Estimates based on identified sightings were comparable to those from the Spanish survey conducted as part of 1989 NASS but were larger if adjusted for a proportion of unidentified large whales. Sei whales were rare except in the southwest of the survey area; the estimate of abundance was 619 (CV 0.34) for identified sightings and 765 (CV 0.43) adjusted for a proportion of unidentified large whales. Minke whale abundance was estimated for shelf and offshore European Atlantic waters as 30,410 (CV 0.34). The model-based estimate was less precise and considerably larger

TESS Discovery of an ultra-short-period planet around the nearby M dwarf LHS 3844

Data from the newly-commissioned \textit{Transiting Exoplanet Survey Satellite} (TESS) has revealed a "hot Earth" around LHS 3844, an M dwarf located 15 pc away. The planet has a radius of $1.32\pm 0.02$ $R_\oplus$ and orbits the star every 11 hours. Although the existence of an atmosphere around such a strongly irradiated planet is questionable, the star is bright enough ($I=11.9$, $K=9.1$) for this possibility to be investigated with transit and occultation spectroscopy. The star's brightness and the planet's short period will also facilitate the measurement of the planet's mass through Doppler spectroscopy.Comment: 10 pages, 4 figures. Submitted to ApJ Letters. This letter makes use of the TESS Alert data, which is currently in a beta test phase, using data from the pipelines at the TESS Science Office and at the TESS Science Processing Operations Cente

Looking for weak ties: using a mixed methods approach to capture elusive connections

Since Granovetter's path breaking work in the 1970s, there has been much discussion about the relevance of weak ties in finding new jobs and generally getting ahead in society. Subsequent research has found evidence to both support and challenge his original theory. However, concerns have also been expressed about the meaning of this concept. What exactly are ‘weak ties’, how are they created and what resources flow through them? In my previous work, I have distinguished between horizontal and vertical ties and the relationships and resources available within them. This paper goes further; drawing on new, mixed methods research with Polish migrants, I explore what types of social ties are useful in contexts of deskilling and finding jobs commensurate with qualifications. Interrogating the concept of ‘weak ties’, I argue that tie strength and ethnic composition are less important than relative social distance and willingness to share valuable resources. I propose that ‘strong ties’ can also act as vertical bridges (or ladders), while ties which are too ‘weak’ may lack necessary trust to share latent resources. I consider the importance of a temporal perspective to explore the dynamism and life cycle of ties over time – as some lapse while others strengthen

People of the British Isles: preliminary analysis of genotypes and surnames in a UK control population

There is a great deal of interest in fine scale population structure in the UK, both as a signature of historical immigration events and because of the effect population structure may have on disease association studies. Although population structure appears to have a minor impact on the current generation of genome-wide association studies, it is likely to play a significant part in the next generation of studies designed to search for rare variants. A powerful way of detecting such structure is to control and document carefully the provenance of the samples involved. Here we describe the collection of a cohort of rural UK samples (The People of the British Isles), aimed at providing a well-characterised UK control population that can be used as a resource by the research community as well as providing fine scale genetic information on the British population. So far, some 4,000 samples have been collected, the majority of which fit the criteria of coming from a rural area and having all four grandparents from approximately the same area. Analysis of the first 3,865 samples that have been geocoded indicates that 75% have a mean distance between grandparental places of birth of 37.3km, and that about 70% of grandparental places of birth can be classed as rural. Preliminary genotyping of 1,057 samples demonstrates the value of these samples for investigating fine scale population structure within the UK, and shows how this can be enhanced by the use of surnames