a commercial fishing vessel began taking on water and sank just off the coast of Galicia according to local search and rescue authorities.  the 2005-built fishing vessel El Cañavera reported that it was in danger of sinking just one nautical mile off Punta Candelaria a cape just north of the port of Cedeira on Galicia's northwestern coast The crew abandoned ship into a liferaft and their vessel sank by the stern about five minutes later.  SAR authorities responded to the call and dispatched a rescue helicopter along with the rescue launches Salvamar Shaula and LS Pardo Bazan The fishing vessel Brisas de Cedeira was nearby it reached the life raft and rescued all four crewmembers in it All were delivered safely to Cedeira.  "They were asking for help and we had them practically in sight we were ten minutes away from them," said the skipper of Brisas de Cedeira "But after five minutes it disappeared." The boat's bow remained in the air as of Monday so the position of the wreck was marked and broadcast to reduce the risk to shipping The cause of the casualty is under investigation Montevideo – Information Office – 23 February HE Vice President and Speaker of the Parliament of the Republic of Uruguay Beatriz Argimon Cedeira hailed HH the Amir Sheikh Tamim bin Hamad Al-Thani's announcement to hold the Shura Council elections in October 2021 This came during HE Beatriz Argimon Cedeira's meeting with Charge d'Affaires of the Embassy of the State of Qatar to the Republic of Uruguay Taleb bin Mohammed Al-Menakhas they reviewed the bilateral cooperation relations between the two countries Adopt well-established policies that achieve the aspirations and interests of the people of Qatar and the strategic interests of the State American Horror Story has become a mainstay at the Primetime Emmy Awards when it comes to make-up As the central plots and themes get more ambitious the designs for everything have to up the ante takes elements of campy fantasy and fuses them with allusions to queer history For prosthetic make-up designer Jeremy Selenfriend and make-up designer Milagros Cedeira this season was rewarding and terrifying but what about the real-life horrors that plagued the gay community in the ’80s NYC takes the uncertainty of the beginnings of the AIDS epidemic and shoots it through a bloody lens and Selenfriend and Cedeira and I start our conversation talking about the difficulty of all the sweat that coats everyone’s bodies but they reveal the surprising amount of work it takes to maintain it The Mai Tai Killer destroys lives to create the perfect specimen but Selenfriend divulges details on just how to make a “Frankenstein Jesus” come to life The same goes for the ghastly death of Hans–the make-up is so detailed that you can almost smell the rot through your screen Selenfriend and Cedeira also talk about calibrating the sickness journeys of Russell Tovey and Joe Mantello’s characters Creator Ryan Murphy has delivered American Horror Story: The Normal Heart but tapping into the true fear that gay men faced during the AIDS crisis American Horror Story: NYC is streaming now on Hulu A24 has dropped a teaser for the latest Spike Lee Joint https://www.youtube.com/watch?v=MZ2V8znYMSk Also starring:.. © 2025 JNews - Premium WordPress news & magazine theme by Jegtheme © 2025 JNews - Premium WordPress news & magazine theme by Jegtheme THOMPSON — The Town of Thompson is poised to possibly see change on a level unseen since big-box retailers Home Depot Staples and Wal-Mart opened stores in the area between Monticello and Kiamesha Lake 5 whether to authorize four upstate gambling resorts with the area around the former Concord Hotel site considered a front-runner for a license A Manhattan-based developer is also proposing China City a massive project combining an amusement park and houses with a hotel and commercial center on land partly in the town someone not named Tony Cellini will assume the supervisor's seat in Thompson The quest to fill the 10-term supervisor's outsize legacy and personality shifts from the campaign trail to the polls in Tuesday's primary Voters will decide whether Ramon Cedeira or Jerry Fielding or will have the Republican line when both face Democratic Bill Rieber in November's general election "I've been involved with the town most of my life," said Fielding who spent 20 years managing the Holiday Mountain ski area when it was town-owned I know what goes on (and) I know what people are complaining about." Both candidates name jobs and economic development as primary concerns and both see approval of the casino referendum as an important step in achieving those goals Fielding recalled how easily kids were able to find work when the region's resort hotels thrived He hitchhiked to the Concord when he was a pre-teen to caddy kids don't have jobs," said the 70-year-old who will still carry the Independence Party line As an upstart challenger to Cellini two years ago but surprised many people by still winning 38 percent of the vote said voters have listed concerns that include the lack of recreational opportunities for kids In addition to increasing youth activities Cedeira advocates for small-business growth Both a casino and China City would bring jobs and much-needed tax revenue and we have to find a way to make them stay up here," he said built in three months and assembled in three days, ‘prefabricated nature’ is a vacation house by spanish firm MYCC architects (formed by carmina casajuana located in the galician municipality of cedeira in a remote location in the northeast corner of the iberian peninsula an area dominated by the imposing presence of the ocean and the forest of eucalyptus trees surrounding it the terrain is surrounded by harvest fields protected by the area’s building codes the volume was wrapped with two materials with the purpose of setting up a dialogue with the landscape the roof and the side facades were covered with viroc® a prefabricated mixture of cement and wood shavings the fibercement has a great strength efficiency in spite of being light and the two main facades of the house were clad with perforated corten trays following the schematized image of a forest silhouette recreating the image of the surrounding vegetation this material was chosen because it is part of the local tradition of fishing towns like cedeira and the gradual and controlled oxidation of which gives the material self-protecting qualities its patina and changing color create a lively image that relates with the natural environment this interplay between the natural and the artificial also benefits the interior spaces where the light that crosses through these silhouettes casts shadows of trees in the different rooms the interior spaces are free-flowing and open up to the landscape of approximately 6 meters in length and 3 in width (the maximum reasonable width to enable their transportation by trailer) organize the program as follows: the first one contains the bedroom which can be divided into two thanks to a blind concealed in the ceiling and which becomes a partition wall when more rooms are needed; the second contains the bathroom and stairs; the third the kitchen; and the last three the living room houses an attic that is a free-flowing space with a double facade that opens up to the sea views towards the southwest and to the forest towards the northeast it is a space that flows out onto the living room without a designated use the corten steel cladding punctured with silouhettes of trees the house combines two different systems: prefabricated construction (2d) for the attic and modular construction (3d) for the ground floor the modules were built in the facilities of the construction company idm in the madrid town of valdemoro these modules were built with a structure of beams and galvanized steel columns and with floor and ceiling slabs of composite decking with reinforced concrete the facade walls are dovetail sandwich panels formed of two sheets of lacquered aluminum and an 80-millimeter-thick polyurethane web plate several layers of waterproofing stretch beneath the furring strips to which the exterior facades are fixed a ventilated air cavity of 20 centimeters lets the structure go through and there is a perimetral panelling of plasterboard with 46 millimeters of rock wool the result is a 30-centimeter-thick wall with a ventilated facade cavity interior cavity and 12 centimeters of total insulation and after making sure that everything fit in properly the different modules and trusses of the building were taken apart to be packed and moved in trailers the whole 700 kilometers separating the factory from the remote seaside site where its was to be installed all the parts were put together again on the designated site in just three days and the finishing touch-ups were done in the following two weeks AXOR presents three bathroom concepts that are not merely places of function but destinations in themselves — sanctuaries of style Setting a solid foundation for the next generation is as important to homebuilder Tony Amaral as building a house that will last generations In keeping with the Amaral family’s commitment started in 2007 13 students of Portuguese descent were honored on Sunday with a scholarship ceremony hosted by the Foundation Antonio Amaral is traditionally hosted alongside an annual golf tournament and picnic drawing close to 800 guests for the celebrations In spite of the restrictions and cancellations the foundation was determined to honor the students and provided $29,000 in scholarships on Sunday “Two weeks ago the family made a decision that the kids were already missing their chance to have a graduation ceremony and prom so we felt this was something they deserved,” said Tony Amaral “With the situation we’re in with COVID we were unable to do the picnic this year but still felt the students deserved their scholarships so today we’re just getting together for a little ceremony,” said program organizer Natalie Amaral Cedeira under the open air pavilion where the festivities are usually held With brief speeches by Flagler County Sheriff Rick Staly and Palm Coast Mayor Milissa Holland both longtime friends of the Amaral family and supporters of the Portuguese community “We’ve stood together for many years in Palm Coast because our purpose has always been the continuity of generations of rich cultural heritage in our community,” noted Holland in her speech Carrying on the Portuguese heritage is part of the scholarship application process and Cedeira said it brings her joy to read the essays as the students include authentic stories they’ve learned from family members who talk about the “old country.” Annalisa Pereira’s application included family history gleaned from her mother Lisa Pereira who feel it’s important to ensure history is passed down Pereira says she’ll follow in the footsteps of her older sisters and is looking forward to a career with Johnson & Johnson Also following in the previous generation’s footsteps Flagler Palm Coast High School graduate Liana Fernandes said it was “awesome” to be chosen for a scholarship by the community that has played a big role in her life she is on track for Daytona State College where she will enter the nursing program with plans to become a labor and delivery nurse we’d always go visit her on holidays – I wouldn’t say I grew up in a hospital but we were always there because of my mom and so it has a special place in my heart,” said Fernandes Christine Fernandes is proud of her daughter and grateful to the foundation for the support “It’s important the Class of 2020 because they lost a lot and it’s nice they still had this to look forward to,” she said the Foundation Antonio Amaral has presented 210 scholarships to youth of Portuguese decent totaling $327,500 Get our news on your inbox! Suscribe x MercoPress, en Español Montevideo, May 6th 2025 - 09:50 UTC were fined £15,500 and £1,300 respectively after pleading guilty on the Summary Court in Stanley to a charge of allowing oil to escape into the territorial waters of the Falkland Islands  The Justices of the Peace (JPs) heard that the ship was maneuvering in Port William whilst awaiting a replacement crew member when it ran aground in Blanco Bay The bow was indented and two hand-size holes were created in the bow The ship managed to free itself a few hours later at high tide and with the help of launches but it is estimated three cubic meters of marine diesel oil escaped from a damaged fuel tank England will return the Malvinas within 25 years Commenting for this story is now closed.If you have a Facebook account, become a fan and comment on our Facebook Page Metrics details Species Distribution Models are commonly used with surface dynamic environmental variables as proxies for prey distribution to characterise marine top predator habitats For oceanic species that spend lot of time at depth surface variables might not be relevant to predict deep-dwelling prey distributions We hypothesised that descriptors of deep-water layers would better predict the deep-diving cetacean distributions than surface variables We combined static variables and dynamic variables integrated over different depth classes of the water column into Generalised Additive Models to predict the distribution of sperm whales Physeter macrocephalus and beaked whales Ziphiidae in the Bay of Biscay We identified which variables best predicted their distribution Although the highest densities of both taxa were predicted near the continental slope and canyons the most important variables for beaked whales appeared to be static variables and surface to subsurface dynamic variables while for sperm whales only surface and deep-water variables were selected This could suggest differences in foraging strategies and in the prey targeted between the two taxa Increasing the use of variables describing the deep-water layers would provide a better understanding of the oceanic species distribution and better assist in the planning of human activities in these habitats surface variables may be partly irrelevant to predict the distribution of their deep-dwelling prey They showed similar performance between the two models highlighting the good performance of environmental modelled data to describe species distribution corresponding to different environments in the water column were defined and relevant environmental variables were extracted for each class GAMs were fitted to assess the explanatory power of these variables the distribution of deep-divers in the Bay of Biscay was predicted using the best models obtained We expected that the use of environmental variables at depth would result in a more accurate modelling of top predator densities and a better understanding of the mechanisms that influence their distributions Comparison between the average prediction obtained from the models that explained 80% of the total Akaike weight and the prediction obtained from the model fitted to the four most important variables If the coefficient of determination (R2) is close to 1 predictions are similar and the average prediction of all models can be approximated by the prediction of the model fitted to the four most important variables The functional relationships between beaked whale and sperm whale individual densities and the four most important and uncorrelated variables Solid lines represent the estimated smooth functions and the blue shaded regions show the approximate 95% confidence intervals The relative density of individuals (individuals per 100 km2) is shown on the y-axis where a zero indicates no effect of the covariate The black rug plot on the x-axis represents the distribution of the data The percentages indicate the importance of the variables calculated by summing the Akaike weights of the models in which they were selected D*: explained deviance; T: temperature; GrT: gradients of temperature; EKE: eddy kinetic energy; m: mean; sd: standard deviation Predicted relative densities of beaked whales (a) and sperm whales (b) obtained from the models that use the four most important and uncorrelated variables The presence of animals at the surface is also probably related to mechanisms at depth in addition to surface environmental variables variables that depicted the water column to identify which variables were the most important for deep-divers since we argued that surface variables might not explain well the physical processes occurring at depth that would influence the beaked and sperm whale distributions Our results highlighted new relationships with the environment allowing to predict the highest densities of beaked whales and sperm whales near the continental slope near canyons and seamounts and in the abyssal plain of the Bay of Biscay we identified different responses between beaked whales subsurface and static variables were selected as the most important variables and sperm whales for which no static variable was selected but only surface and deep-water variables At-depth dynamic variables should be used in other areas such as the North West Atlantic or the Mediterranean Sea to determine whether the difference in importance of static surface and deep-water variables between beaked whales and sperm whales would also be observed and would be consistent with whale dietary data available in these areas The use of smaller segments in the analyses could help refine the understanding of the processes that influence the concentration of these species within the canyons mixed layer depth) provided by an ocean circulation model to model distribution of cetaceans in the California Current Ecosystem They both showed that variables obtained from ocean circulation models improved the explanatory power of the distribution models prey models need refinements to better characterise the prey of deep-diving cetaceans and thus to improve whale distribution models Our results identified areas of concentration that had not been identified until now in some canyons of the Bay of Biscay (e.g such as the use of other variables that characterise the water column but our results confirmed the utility of deep-water variables in SDMs to model the distribution of top predators linked to meso and bathypelagic areas for a better characterising of their habitats Increasing the use of these variables should be considered to improve the tools available for the planning of human activities especially for species that would be closely linked to processes at depth The availability of modelled variables describing deep water-ocean layers should be incorporated into future studies to improve the characterisation of the habitats of top predators Study area showing assembled survey effort (a), along with beaked whale (b) and sperm whale (c) sightings recorded during all surveys. Surveys were carried out along transects following a line-transect methodology (survey details are provided in Appendix A) Sightings were classified by group sizes with each point representing one group of individuals and point size representing the number of animals in a group we used the number of individuals to estimate densities of individuals Schematic representation of environmental variables used in habitat-based density models and depth classes Orange arrows represent the four depth classes (Surface 200–600 m and 600–2000 m) and environmental variables are written in black the central waters of the North Atlantic Ocean between 200 and 600 m (named “200–600 m”) and the Mediterranean waters between 600 and 2000 m (named “600–2000 m”) Although water masses between 600 and 1500 m and between 1500 and 3000 m are different (see 4.1) we considered no changes in the water masses from 1500 to 2000 m and grouped them into one class To model species distributions, it was necessary to extract environmental variables. We considered static and dynamic variables that can affect the distribution of beaked whales and sperm whales (Table 3) Static variables remained stable over time and were independent from depth classes while dynamic variables were extracted in each depth class and varied over time All static variables were resampled at a 0.083° resolution to match the resolution of the dynamic variables Correlation matrix of environmental variables This matrix was calculated using the Pearson coefficient; the larger and darker the circle the higher the correlation between the two environmental variables; variables are considered correlated for values below − 0.5 and above 0.5 CanArea: surface of canyons; T: temperature GrT: gradients of temperature; EKE: eddy kinetic energy; m: mean; sd: standard deviation; surf: surface; 0–200: 0–200 m; 200–600: 200–600 m; 600–2000: 600-2000 m some variables are probably very similar and correlated it is not possible to choose a best model among all tested models since the models are equivalent and they must all be integrated to produce an average prediction of species distribution This can be cumbersome in terms of calculations and difficult to interpret it is more suitable to obtain a single model we determined the importance of each variable by summing the Akaike weights of the models in which the variable was selected and ranked all variables A model using the first four variables was then fitted while ensuring a non-correlation of the variables (if variables were correlated the next uncorrelated ranked variable was chosen) A prediction of relative densities (in number of animals per pixel) was produced from this model at a 0.083° resolution and compared to the average prediction obtained from the models that explained 80% of the total Akaike weight We considered only the models that explained 80% of the Akaike weight because beyond this threshold the models were negligible (very low explained deviances and very high AICs) If the coefficient of determination (R2) of the regression line established between the values of the average prediction and the values of the prediction obtained from the four most important variables was close to 1 predictions were similar and the average prediction of all models could be approximated by the prediction of the model fitted to the four most important variables The four variables could therefore be used to obtain functional relationships and to predict the relative densities of beaked whales and sperm whales in the Bay of Biscay all models had to be considered to predict the species densities There were not enough data to fit a model by month or by season (the number of individuals in winter was too low) so we fitted models to all data of beaked whales and sperm whales and obtained climatological predictions maps for all seasons combined in the 1998–2016 period although most of sighting data were collected in summer and the prediction maps most likely reflected the summer species distribution The uncertainties associated with the predictions were also estimated as the standard deviation associated with the predicted relative densities; high values indicated high errors associated with density estimates it should be noted that the uncertainty associated with the model prediction with the four most important variables was certainly lower than the uncertainty associated with the mean prediction of all models and it was therefore underestimated All sighting and effort data used in this study are available in the GitHub: https://github.com/avirgi01/DeepVariables.git All data providers can be contacted via the email addresses provided in the data files Species distribution models: Ecological explanation and prediction across space and time Application of species distribution models and conservation planning software to the design of a reserve network for the riverine fishes of northeastern Mesoamerica Comparing the performance of species distribution models of Zostera marina: Implications for conservation A systematic review of marine-based species distribution models (SDMs) with recommendations for best practice Habitat-based cetacean density models for the US Atlantic and Gulf of Mexico How does ocean seasonality drive habitat preferences of highly mobile top predators Part I: The north-western Mediterranean Sea Using remote-sensing environmental and fishery data to map potential Yellowfin Tuna habitats in the tropical pacific Ocean Predicting habitat suitability for basking sharks (Cetorhinus maximus) in UK waters using ensemble ecological niche modelling Impacts of climate change on marine top predators: Advances and future challenges Current global risks to marine mammals: Taking stock of the threats Marine litter: One of the major threats for marine mammals Outcomes from the European Cetacean Society workshop Spatial match-mismatch in the Benguela upwelling zone: should we expect chlorophyll and sea-surface temperature to predict marine predator distributions? and beaked whale foraging habitat in the tongue of the ocean Marine megafauna niche coexistence and hotspot areas in a temperate ecosystem abundance and habitat use of deep diving cetaceans in the North-East Atlantic Identifying important juvenile dusky shark habitat in the northwest atlantic ocean using acoustic telemetry and spatial modeling Marine bird and cetacean associations with bathymetric habitats and shallow-water topographies: implications for trophic transfer and conservation In Encyclopedia of Marine Mammal (eds Perrin Prey preferences among the community of deep-diving odontocetes from the Bay of Biscay The challenge of habitat modelling for threatened low density species using heterogeneous data: The case of Cuvier’s beaked whales in the Mediterranean Multi-scale analysis reveals changing distribution patterns and the influence of social structure on the habitat use of an endangered marine predator the sperm whale Physeter macrocephalus in the Western Mediterranean Sea Deep-diving foraging behaviour of sperm whales (Physeter macrocephalus) Spatio-temporal variation in click production rates of beaked whales: Implications for passive acoustic density estimation Diving behaviour of Cuvier’s beaked whales (Ziphius cavirostris) off Cape Hatteras Integrating dynamic subsurface habitat metrics into species distribution models Moving towards dynamic ocean management: How well do modeled ocean products predict species distributions? On confidence intervals for generalized additive models based on penalized regression splines Combining multiple visual surveys to model the habitat of deep-diving cetaceans at the basin scale Model Selection and Multimodel Inference (Springer Systematics and Biogeography of Cephalopods (Smithsonian Institution Press The relative importance of habitat complexity and surface area in assessing biodiversity: Fractal application on rocky shores Three anticyclonic slope water oceanic eDDIES (SWODDIES) in the Southern Bay of Biscay in 1990 Physical processes and hydrological structures related to the Bay of Biscay anchovy The importance of oceanographic fronts to marine birds and mammals of the southern oceans Ocean fronts drive marine fishery production and biogeochemical cycling and habitat characteristics of toothed cetaceans in the Bay of Biscay and adjacent waters from platform-of-opportunity Data Characterization of beaked whale (Ziphiidae) and sperm whale (Physeter macrocephalus) summer habitat in shelf-edge and deeper waters off the Northeast U.S. Aspects of the distribution of Cuvier’s beaked whale (Ziphius cavirostris) in relation to topographic features in the Pelagos Sanctuary (north-western Mediterranean Sea) Occurrence and spatio-temporal distribution of sperm whale (Physeter macrocephalus) in the submarine canyon of Cuma (Tyrrhenian Sea Submarine canyons as important habitat for cetaceans with special reference to the Gully: A review Millot, C. & Taupier-Letage, I. Circulation in the Mediterranean Sea. In: Saliot, A. (eds) The Mediterranean Sea. Handbook of Environmental Chemistry, vol 5K. Springer, Berlin, Heidelberg. (2005). https://doi.org/10.1007/b107143 Robbins, J. R., Bell, E., Potts, J., Babey, L. & Marley, S. A. Likely year-round presence of beaked whales in the Bay of Biscay. Hydrobiologia https://doi.org/10.1007/s10750-022-04822-y (2022) and movements of Cuvier’s (Ziphius cavirostris) and Blainville’s (Mesoplodon densirostris) beaked whales off the island of Hawai’i Movements and distribution of northern bottlenose whales on the Scotian Slope and in adjacent waters Extrapolating cetacean densities beyond surveyed regions: Habitat-based predictions in the circumtropical belt multimodel inference and model averaging in behavioural ecology using Akaike’s information criterion Predicting cetacean habitats from their energetic needs and the distribution of their prey in two contrasted tropical regions Towards a better characterisation of deep-diving whales’ distributions by using prey distribution model outputs? Eco-informatics for predicting the catchability of a pelagic fish in near real time Sperm whale diving behavior monitored using a suction-cup-attached TDR tag Sperm whale dive behavior characteristics derived from intermediate-duration archival tag data Movements and dive behaviour of a toothfish-depredating killer and sperm whale CA: Environmental Systems Research Institute (2016) Marine geospatial ecology tools: An integrated framework for ecological geoprocessing with ArcGIS Distance Sampling: Methods and Applications (Springer International Publishing Comparing implementations of global and local indicators of spatial association Diving behaviour of Cuvier’s (Ziphius cavirostris) and Blainville’s (Mesoplodon densirostris) beaked whales in Hawai‘i raster: Geographic data analysis and modeling https://CRAN.R-project.org/package=raster (2020) grec: Gradient-based recognition of spatial patterns in environmental data A Poisson-Gamma model for analysis of ecological non-negative continuous data Fast stable restricted maximum likelihood and marginal likelihood estimation of semiparametric generalized linear models Predicting cetacean and seabird habitats across a productivity gradient in the South Pacific gyre Wei, T. & Simko, V. R package ‘corrplot’: Visualization of a correlation matrix (Version 0.84). https://github.com/taiyun/corrplot (2017) qpcR: Modelling and analysis of real‐time PCR data https://CRAN.R-project.org/package=qpcR (2018) The basics of financial econometrics: Tools Habitat-based density models for three cetacean species off southern california illustrate pronounced seasonal differences Fundamentals of ocean renewable energy: Generating electricity from the sea Performance evaluation of cetacean species distribution models developed using generalized additive models and boosted regression trees Download references We are grateful to the many observers who participated in the surveys and collected all the data but also the ships’ captains We thank Phil Hammond and his team for providing SCANS and CODA survey data THUNNUS survey was carried out thanks to the collaboration of the General Directorate of Fisheries and Maritime Affairs We thank the Direction Générale de l'Armement (DGA) ML was funded by a Ramón y Cajal (RYC-2012-09897) postdoctoral contract of the Spanish Ministry of Economy This study is a contribution to the CHALLENGES (CTM2013-47032-R) project of the Spanish Ministry of Economy We would particularly like to thank Matthieu Authier for his advice in carrying out the analyses We thank the two reviewers for their careful reading of our manuscript and for their helpful comments Basque Research and Technology Alliance (BRTA) Centre d’Etudes Biologiques de Chizé - La Rochelle Formal analysis & Writing—Original Draft The authors declare no competing interests Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Download citation DOI: https://doi.org/10.1038/s41598-022-13546-x Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Sign up for the Nature Briefing: Anthropocene newsletter — what matters in anthropocene research Sullivan County BOCES held its Recognition Ceremony for 159 graduating Career & Technical Education students at the Liberty Central School Joseph McDoal (RCS) and Alyssa Vilela (MCS) spoke at the ceremony on behalf of their classmates Both expressed their gratitude to BOCES for providing them with the opportunity to attend the New Vision Health Program They also spoke about their Career & Tech experience and how it influenced their lives and futures in a positive way by providing an opportunity to challenge themselves and grow Health Occupations student; and Ariana Fassetta (TVCS) Culinary Arts student; also spoke during the ceremony Both talked about their Career and Tech experience and the impact it had on their lives Fassetta ended her talk by telling classmates It’s time the world gets to see how wonderful we are.” Special awards and scholarships were given to the following students: Catskill Region AACA Antique Car Club Scholarship Gene Haas Foundation Student Manufacturing Scholarships Proud to Be Sullivan: Choosing Your Attitude Training SUPA Public Affairs 101 and SCCC Speech 101 Roscoe Central School was awarded an Attendance Certificate for the students with the highest attendance record for the 2014-2015 school year For more information about programs available through the Career & Technical Education Center Library funding is under threat. Find out how you can show up for libraries: ala.org/showup CHICAGO — How should LIS envision its young adult users? Now showcasing an even more rigorous debate about the theory and practice of YA librarianship, the new second edition of “Transforming Young Adult Services,” published by ALA Neal-Schuman has been updated and expanded by author and editor Anthony Bernier to incorporate recent advances in critical youth studies evidence-based treatment that offers LIS instructors and practitioners a valuable tool for aligning YA services to more fully reflect our diverse populations of young people this collection delves deeply into such topics as: is professor at California’s San José State University School of Information The iSchool has awarded him Distinguished Service He received two National Leadership Grants from the Institute of Museum and Library Services (on library spaces for young people) one from ALA’s Diversity Research Committee and another from the Association for Library and Information Science Education (ALISE) in support of his research on first-generation graduate students He also served a four-year term on ALA’s Committee on Accreditation chaired several national professional and academic associations was recently elected chair of ALA’s Library History Round Table and currently writes the regular “YA Strike Zone” column for Voice of Youth Advocates (VOYA) A practicing YA specialist librarian and administrator for 15 years he designed the first purpose-built library space for teenaged youth the Los Angeles Public Library’s acclaimed Teen’Scape and produced nationally recognized youth outreach and programming models "Transforming Young Adult Services, Second Edition" "Create, Innovate, and Serve: A Radical Approach to Children's and Youth Programming" "Teaching Media Literacy, Second Edition" Today, the U.S. District Court for the District of Columbia granted a temporary restraining order to block the Trump Administration’s dismantling of the Institute of Museum and Library Services (IMLS). American Library Association, AFSCME Challenge Trump Administration Gutting of Institute of Museum and Library Services The American Library Association (ALA) today released the highly anticipated Top 10 Most Challenged Books List. An executive order issued by the Trump administration on Friday night, March 14, calls for the elimination of the Institute of Museum and Library Services, the nation’s only federal agency for America’s libraries. The American Library Association launched a new supporter program on February 10, 2025, inviting the public to join the fight to protect libraries and library professionals at a pivotal moment in our country’s history. The American Library Association responds to the Department of Education's dismissal of complaints about censorship and discrimination: the "effort to terminate protections... advances the demonstrably false claim that book bans are not real." Today the American Library Association (ALA) launched Show Up for Our Libraries, a campaign to harness the collective power of library advocates to influence elected leaders and policymakers. The American Library Association extends our deepest sympathies to those who have been affected by and to those who have lost everything during the Los Angeles area fires. The Public Library Association (PLA) has selected more than 139 public libraries across 42 states to host digital literacy workshops, powered by a generous $2.7 million contribution from AT&T. James W. Lewis has made the largest individual bequest to the American Library Association in the association’s history. © 1996–2025 American Library Association The Monticello School District made four unwanted school buses disappear almost into thin air. But there was no sleight of hand involved. All it took was a computer to unload each of the 15-ton buses. "It was like David Copperfield, only on eBay," said schools Superintendent Daniel Teplesky. For its efforts, the school district managed to rake in nearly $38,000 from the four separate auctions at the end of May. Please enable JS and disable any ad blocker Babou Diouf tells Nacho Doce about the perilous journey that brought him to Spain where foreign workers are crucial to the survival of the EU’s largest fishing fleet I would like to be emailed about offers, events and updates from The Independent. Read our Privacy notice Watching news of Senegalese migrants arriving on the Canary Islands stirs memories for Babou Diouf of the same perilous journey he undertook 17 years ago and his arduous path to his new home – Burela, on Spain’s northern coast. Diouf, 46, a fisherman from Bassoul in Senegal’s Sine Saloum delta, was part of a migration surge in 2006 from West Africa through Spain’s Canary Islands, which lie around 100km (60 miles) off Africa’s northwestern coast. More than 30,000 migrants arrived that year, fleeing poverty exacerbated by a dramatic plunge in coastal fish stocks, partly due to industrial fishing by European Union states, according to academics, NGOs, and migrants. The 2006 record for migrant arrivals through the Canaries was broken last year. Nearly 7,000 died attempting the crossing in 2023, according to rights group Caminando Fronteras (Walking Borders). “To see rafts arriving in Spain is very difficult,” said Diouf. “To cross the ocean without knowing what you’re facing – you’re facing death.” Deprived of his livelihood in Senegal, Diouf ventured north. Today, his fishing experience has secured him a new life in Spain, where the EU’s largest fishing fleet, shunned by ever more Spanish workers, is recruiting foreigners to survive. The fishing port of Burela has 44 nationalities among its 9,450 residents, including 90 men from Senegal and 244 from Cape Verde, according to the mayor’s office. Foreign workers make up about seven out of 10 crew in Burela’s fishing fleet, said Juan Carlos Otero of Burela’s boat owners’ association. The Peruvians were the first to arrive in 2000 when locals left to work in a new steel plant, said Otero. Indonesians are so valued for their longline fishing skills that boat owners pay for their flights to Spain. Others, like the Senegalese, find work through word of mouth or by turning up at the dock where, if they have residence permits, they are then offered contracts. Immigration, largely welcomed by locals, is changing the town. Diouf regularly visits a recently built mosque. Cape Verdean women serve coffee and breakfast at A’Mares, a restaurant in the port. Working alongside Indonesians, Senegalese and Spaniards on the Sarridal vessel, Diouf is a whirl of activity, hauling in nets and cleaning and boxing hake during 14-hour shifts. The boat’s captain, Francisco Gonzalez, said Spain’s fishing industry can’t survive without migrants. Join thought-provoking conversations, follow other Independent readers and see their replies Captain Francisco Gonzalez looks at a map inside the Sarridal ship before a fishing outing to the Atlantic Ocean, at Cedeira’s port, Galicia, Spain Metrics details Disruption of the histone modification patterns is one of the most common features of human tumors few genetic alterations in the histone modifier genes have been described in tumorigenesis Herein we show that the histone methyltransferase SETDB1 undergoes gene amplification in non-small and small lung cancer cell lines and primary tumors The existence of additional copies of the SETDB1 gene in these transformed cells is associated with higher levels of the corresponding mRNA and protein the depletion of SETDB1 expression in amplified cells reduces cancer growth in cell culture and nude mice models whereas its overexpression increases the tumor invasiveness The increased gene dosage of SETDB1 is also associated with enhanced sensitivity to the growth inhibitory effect mediated by the SETDB1-interfering drug mithramycin the findings identify SETDB1 as a bona fide oncogene undergoing gene amplification-associated activation in lung cancer and suggest its potential for new therapeutic strategies we examined whether the SETDB1 gene amplification occurs in lung cancer cell lines and primary tumors and studied its impact on mRNA and protein expression levels its functional role in lung cancer growth and its potential value as a biomarker for predicting the response to particular chemotherapeutic agents in lung tumors A telomeric BAC clone located in the telomeric 1p36.23 region was used as a control The BACs were obtained from the BACPAC Resource Center at the Children’s Hospital Oakland Research Institute (Oakland SETDB1 and telomeric probes were labeled with Spectrum Green and Red dUTP (Abbott using a CGH Nick Translation Reagent Kit (Abbott Molecular Inc. The samples were counterstained with 4',6-diamidino-2-phenylindole in Vectashield antifade solution (Burlingame Gene amplification was observed in the interphases of NCI-H1437 Probes were verified to give a single signal on normal commercial lymphocyte metaphase slides (CGH Reagents Quantitative reverse transcription–PCR (c) and western blot (d) demonstrate higher levels of SETDB1 mRNA and protein (ab12317 NCI-H1395 and DMS-273) than that in unamplified cells Growth-promoting effects of SETDB1 in lung cancer (a) Stable downregulation of the SETDB1 gene by short hairpins using two different target sequences for DMS-273 (clones A30/A31 and clone B32-63) and NCI-H1437 (clones A56-B and B46-9) SETDB1 shRNA sequences are available upon request (b) The short hairpin SETDB1-depleted cells were less viable in the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay than in the untransfected or scrambled shRNA-transfected cells (P-values obtained by the analysis of variance (ANOVA) test) (c) The colony formation assay showed that DMS-273 and NCI-H1437 cells stably transfected with the shRNA against SETDB1 formed significantly fewer colonies than scrambled shRNA-transfected cells (P-values obtained by the ANOVA test) (d) Effect of SETDB1 shRNA-mediated depletion on the growth of DMS-273 and NCI-H1437 xenografts in nude mice Tumor volume was monitored over time and the tumor was excised and weighed at 30 days There was a significant decrease in tumor weight in the SETDB1 shRNA-stably transfected cells (P-values obtained by the ANOVA test) Impact of SETDB1 on invasiveness and chemosensitivity (a) Effect of SETDB1 on the invasion potential of A549 cells determined by the matrigel invasion assay Cells were transfected with 3 μg of Flag-SETDB1 or empty vector in 60 mm dishes cells were stimulated or not with phorbol myristate acetate (PMA) plus ionomycin (Io) for 30 min and 5 × 104 cells were resuspended in serum-free media and added to the upper compartment of a transwell coated with 1 mg/ml Matrigel (BD Biosciences Media with 10% fetal bovine serum was added in the lower compartment and cells were incubated at 37 °C for 42 h Invasive cells were fixed with phosphate-buffered saline 4% paraformaldehide stained with 0.5% violet crystal and visualized and photographed under a × 10 magnification objective with a microscope Invasive cells were counted using ImageJ 1.45s (Wayne Rasband USA) and percentage of invasive cells were represented Results are the mean of at least three experiments by duplicate and the significance was determined using analysis of variance test (b) Cancer cells harboring the SETDB1 gene amplification are sensitive to the decrease in cell viability caused by mithramycin 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays in control-scrambled shRNA DMS-273-transfected cells in comparison with three shRNA-stable downregulated SETDB1 clones (A21 A30 and A31) show enhanced inhibition of viability in cells with SETDB1 gene amplification-mediated overexpression (b) Immunohistochemistry for SETDB1 (HPA018142 USA) shows overexpression of the protein in the above shown three primary lung tumors harboring SETDB1 gene amplification Minimal expression is detected in the unamplified cases (4 and 5) (c) Association between SETDB1 gene amplification and overexpression in the studied fifty-nine cases is shown our results indicate that the histone methyltransferase SETDB1 undergoes gene amplification in the natural history of lung tumorigenesis in non-small and small cell lung cancers The copy-number gain for SETDB1 is associated with overexpression of the transcript and protein in lung cancer cell lines and primary tumors SETDB1 exerts growth enhancing activity in vitro and in vivo as we have shown by depletion and transfection experiments in cell culture and in the nude mice model Lung cancer cells carrying a SETDB1 gene amplification event are also more sensitive to the antiproliferative action mediated by the antitumoral antibiotic mithramycin our results suggest an oncogenic role for SETDB1 in lung carcinogenesis and raise the possibility of exploring new targeted therapies for the subset of lung tumor patients harboring the SETDB1 gene amplification event Aberrant epigenetic landscape in cancer: how cellular identity goes awry Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer Global histone modification patterns predict risk of prostate cancer recurrence Unsafe SETs: histone lysine methyltransferases and cancer Epigenetics provides a new generation of oncogenes and tumour-suppressor genes Key roles of histone methyltransferase and demethylase in leukemogenesis Cancer epigenetics reaches mainstream oncology Down-regulation of human DAB2IP gene expression mediated by polycomb Ezh2 complex and histone deacetylase in prostate cancer Integrative genomics analysis reveals silencing of beta-adrenergic signaling by polycomb in prostate cancer The gene encoding the prostatic tumor suppressor PSP94 is a target for repression by the Polycomb group protein EZH2 Silencing of kruppel-like factor 2 by the histone methyltransferase EZH2 in human cancer The polycomb group protein EZH2 is involved in progression of prostate cancer essential for proliferation and amplified in cancer EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells Proc Natl Acad Sci USA 2003; 100: 11606–11611 Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity modifies chromatin and is directly involved in infant acute leukaemia hDOT1L links histone methylation to leukemogenesis Epigenetic inactivation of the Sotos overgrowth syndrome gene histone methyltransferase NSD1 in human neuroblastoma and glioma Proc Natl Acad Sci USA 2009; 106: 21830–21835 The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3 SETDB1: a novel KAP-1-associated histone H3 lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins a novel histone H3-specific methyltransferase that interacts with ERG transcription factor The histone methyltransferase SETDB1 and the DNA methyltransferase DNMT3A interact directly and localize to promoters silenced in cancer cells Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET SetDB1 contributes to repression of genes encoding developmental regulators and maintenance of ES cell state DNA methylation and SETDB1/H3K9me3 regulate predominantly distinct sets of genes Dual functions of histone-lysine N-methyltransferase Setdb1 protein at promyelocytic leukemia-nuclear body (PML-NB): maintaining PML-NB structure and regulating the expression of its associated genes Deregulation of histone lysine methyltransferases contributes to oncogenic transformation of human bronchoepithelial cells Treatment of HER2-positive breast cancer: current status and future perspectives The cancer cell line encyclopedia enables predictive modeling of anticancer drug sensitivity regulates glioblastoma-derived neurosphere cell differenciation and tumor propagation Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7 Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia BET bromodomain inhibition as a therapeutic strategy to target c-Myc Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia ESET/SETDB1 gene expression and histone H3 (K9) trimethylation in Huntington's disease Proc Natl Acad Sci USA 2006; 103: 19176–19181 Expression of beta-galactosidase under the control of the human c-myc promoter in transgenic mice is inhibited by mithramycin Comparative genomic hybridization analysis detects frequent and 8q in human non-small cell lung carcinomas Molecular cytogenetic analysis of non-small cell lung carcinoma by spectral karyotyping and comparative genomic hybridization Assessment of molecular events in squamous and non-squamous cell lung carcinoma Chromosomal imbalances of primary and metastasic lung adenocarcinomas Distinct patterns of genetic alterations in adenocarcinoma and squamous cell carcinoma of the lung Genomic alterations detected by comparative genomic hybridization in primary lung adenocarcinomas with special reference to the relationship with DNA ploidy Comprenhensive genomic characterization of squamous cell lung cancers Differential pathogenesis of lung adenocarcinoma subtypes involving sequence mutations Download references This work was supported by the European Community’s Seventh Framework Programme (FP7/2007-2013) under Grant agreement number HEALTH-F2-2010-258677—CURELUNG project the Institute of Health Carlos III (ISCIII)—PI10/02992 Kutxa-Fundación INBIOMED and the Health and Science Departments of the Catalan Government (Generalitat de Catalunya) Cancer Epigenetics and Biology Progrm (PEBC) Bellvitge Biomedical Research Institute (IDIBELL) Experimental Therapeutics and Translational Oncology Program Instituto de Biología Molecular y Celular del Cáncer Instituto de Investigación Biomédica de Salamanca (IBSAL) Centro Hospitalar São João/Medical Faculty and Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) Portuguese Oncology Institute and Biomedical Sciences Institute (ICBAS) Institucio Catalana de Recerca i Estudis Avançats (ICREA) The authors declare no conflict of interest Supplementary Information accompanies this paper on the Oncogene website This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ Download citation Metrics details VRK2 is a novel Ser-Thr kinase whose VRK2A isoform is located in the endoplasmic reticulum and mitochondrial membranes We have studied the potential role that VRK2A has in the regulation of mitochondrial-mediated apoptosis VRK2A can regulate the intrinsic apoptotic pathway in two different ways The VRK2A protein directly interacts with Bcl-xL VRK2A does not compete with Bax for interaction with Bcl-xL and these proteins can form a complex that reduces apoptosis high VRK2 levels confer protection against apoptosis VRK2 knockdown results in an increased expression of BAX gene expression that is mediated by its proximal promoter thus VRK2A behaves as a negative regulator of BAX Low levels of VRK2A causes an increase in mitochondrial Bax protein level leading to an increase in the release of cytochrome C and caspase activation VRK2A loss results in an increase in cell death that can be detected by an increase in annexinV+ cells Low levels of VRK2A increase cell sensitivity to induction of apoptosis by chemotherapeutic drugs like camptothecin or doxorubicin We conclude that VRK2A protein is a novel modulator of apoptosis apoptosis is also modulated by additional cellular proteins which in general are not known we hypothesized that VRK2A might have a protective role against apoptosis if it could interact with proteins that participate in the mechanisms that trigger or execute apoptosis in human cells it has been identified that VRK2A levels can modulate apoptosis in two different ways by its interaction with Bcl-xL and by regulation of BAX gene expression Subcellular localization and interactions of VRK2A with apoptotic proteins (a) Colocalization of endogenous VRK2 with transfected Bcl-xL detected by confocal microscopy in A549 cells VRK2 was detected with a rabbit polyclonal antibody and Bcl-xL with a monoclonal antibody (b) Colocalization of VRK2 with transfected Bax detected by confocal microscopy in A549 cells Bax was detected with a monoclonal antibody (c) Detection of interaction between VRK2 and Bcl-xL HeLa cells were transfected with plasmid pCEFL-GST-VRK2A that expresses GST-VRK2A and used in a pulldown assay in which the associated protein were detected in immunoblots using specific antibodies for GST that detects transfected GST and GST-VRK2 and specific antibodies for detection of endogenous Bcl-2 The ratio of GST-VRK2/actin ranges between 0.72–0.66 in the three bots respectively.(d) Mapping the interaction between VRK2A and Bcl-xL The region of interaction between VRK2A and Bcl-xL was performed by pulldown assays with different constructs of the VRK2A protein which is summarized in a diagram to the right VRK2B is a spliced variant that has 397 aminoa cids and is identical to the N-terminal region of VRK2A and thus it was independent of VRK2 kinase activity The potential interaction of VRK2A with BH3-only proteins, such as PUMAα, BAD and Binp3L was ruled out using a similar approach (Supplementary Figure S1) Bcl-xL and Bax detected in pulldown assays (a) Effect of increasing Bax in the presence of saturating amounts of VRK2A and Bcl-xL (b) Effect of increasing Bcl-xL in the presence of saturating VRK2A and Bax (c) Effect of increasing VRK2A in the presence of saturating Bcl-xL and Bax HEK293T cells were transfected with the indicated amounts of plasmids pCEFL-GST-VRK2A The proteins in the input lysates are shown at the top The proteins present in the pulldown are shown at the bottom and were detected with the corresponding specific antibody To determine if VRK2A was able to phosphorylate either Bcl-xL or Bax different in vitro kinase assays were performed VRK2A did not phosphorylate any of these proteins (not shown) (a) VRK2 knockdown in A549 cells modified Bax protein levels The total Bax protein was detected with the 2D2 antibody a reduction in the levels of antiapoptotic proteins Bcl-xL and Bcl-2 was detected in immunoblots (b) VRK2 knockdown increased the level of BAX gene expression in A549 cells determined by qt-RT-PCR A549 cells were mock transfected or transfected with the indicated SiRNA and 3 days after transfection total RNA was extracted and the level of Bax and GAPDH mRNA levels were determined by qt-RT-PCR The results from four independent experiments are shown (c) Reduction of VRK2A levels activated expression from the promoter of BAX A549 cells were transfected with si-Control (Si-Ct) or two different si-VRK2 (06 and 08 cells were transfected with 1 μg of pGL3-Bax-Luc (–687 to –318) and cells extracts were used to measure the luciferase activity The results are the mean of three independent experiments and the mean with the standard deviation is shown (d) VRK2A overexpression inhibited expression directed by the BAX gene promoter that is induced in response to camptothecin A549 cells were treated for 6 hours with 5 μM camptothecin followed by transfection with 1 μg of empty vector (pCEFL-HA) or plasmid expressing VRK2A (pCEFL-HA-VRK2A) or VRK1 (pCEFL-HA-VRK1) together with the reporter pGL3-Bax-Luc from three independent experiments is shown To determine if the effect on Bax protein levels was a consequence of an effect mediated by regulation of BAX gene expression, the level of BAX mRNA was determined by qt-RT-PCR. Loss of VRK2 using two different siRNAs resulted in a significant increase in the expression of BAX mRNA (Figure 3b) this result indicated that VRK2 inhibited BAX gene expression BCL2 and Bcl-xl mRNA levels were also analysed but no differences in gene expression were detected after VRK2 knockdown (not shown) All these data indicated that VRK2A inhibited transcription directed by the BAX gene promoter Low levels of VRK2 facilitated release of cytochrome c and PARP processing (a) VRK2 knockdown with si-VRK2-06 and si-Control (si-Ct) in three cell lines lung carcinomas A549 and H1299 and cervical carcinoma HeLa The reduction in endogenous protein level and its quantification 4 days after transfection are shown Endogenous VRK2 protein was detected with a rabbit polyclonal antibody (b) The release of cytochrome c was determined by its detection in cytosolic and mitochondrial fractions in extracts from HeLa cells prepared 96 h after siRNA transfection The effect of si-VRK2-06 is shown in the top gel panel and quantification of cytochrome c distribution in the two fractions represented as percentage of band intensity respect to the corresponding marker Actin and cytochrome c oxidase II were used as markers for the cytosolic and mitochondrial fractions respectively (c) Effect of VRK2 knockdown on processing of PARP The proteolytic processing of PARP was determined in a western blot and quantification of the 115 and 85-kDa bands represented as percentage of band intensity Immunoblots show a representative experiment and quantifications show the mean and S.D These results indicated that loss of VRK2A facilitated induction of the intrinsic apoptotic pathway and we concluded that high levels of VRK2A have a protective role as inhibitors of apoptosis Low levels of VRK2 sensitized cells to camptothecin treatment (a) VRK2 knockdown was induced in A549 cells These cells were treated with 5 μM of camptothecin and the distribution of cytochrome c and Bax were determined in cytosolic and membrane fractions at different time points after camptothecin addition Fractionated extracts were used for western blot analysis with the corresponding antibodies (b) Low VRK2 facilitated activation of caspases in response to treatment with 5 μM camptothecin VRK2 knockdown was induced by two different siRNA si-VRK2-06 (at the top) or si-VRK-2M (at the bottom) and caspase activation was determined by PARP processing PARP was determined by immunoblot with a specific antibody at different time points after camptothecin addition to A549 cell culture (c) Loss of VRK2 facilitated induction of DNA damage by camptothecin A549 cells were transfected with si-Control or si-VRK2-06 and 96 hours later they were treated with 5 μM of camptothecin A TUNEL assay was performed to detect the presence of free DNA ends at different time points Cells labelled with fluorescein-12-dTUP (rTdT) and propidium iodide were analysed in a fluorescence microscope Cell images with fluorescence are shown in the left panel and in the right panel the quantification of TUNEL positive cells are shown as a function of time following treatment with camptothecin Effect of VRK2 knockdown on cell death induced by camptothecin treatment VRK2 was knocked down in A549 cells and after 3 days cells were treated with camptothecin for the indicated time points (a) Effect of VRK2 knockdown on the sensitivity of A549 cells to camptothecin detected by alterations in the plasma membrane with annexin V+ Cells were stained with AnnexinV-FITC and positive cells were counted by flow cytometry (b) Effect of VRK2 knockdown on A549 cell viability after camptothecin treatment Viability was determined by Trypan blue dye exclusion assay (c) Effect of VRK2 knockdown on mitochondrial membrane potential in the response to camptothecin was determined by loss of DIOC6 fluorescence in damaged cells Effect of camptothecin (5 μM) on A549 cells and detection of propidium iodide staining by flow cytometry The fragmented DNA was detected in the sub-G0/G1 window (bar) Apoptosis is a tightly regulated process in which many of the components that modulate this form of cell death are still unknown Regulation of apoptosis can be achieved by multiple mechanisms One is by novel proteins that form a complex with apoptotic or antiapoptotic proteins The other is by regulating the expression of apoptotic or anti-apoptotic genes and altering their intracellular levels there is an alteration in mitochondrial membrane and it is likely that other mitochondrial membrane protein complexes remain to be identified but they can modulate the magnitude of the apoptotic response but it is possible that VRK2A in the mitochondrial membrane complex might phosphorylate some protein not yet identified This might either interfere with Bax incorporation or alternatively alter mitochondrial membranes facilitating its permeability and cytochrome c release Variations in intracellular VRK2A protein levels This effect is mediated by the regulation of the BAX promoter by VRK2A functioning as a negative regulator of this promoter The VRK2A function as a transcriptional repressor opens up a new aspect in the role of VRK2 as a regulator of transcription VRK2A is acting at two different levels in the modulation of the cell response to induction of apoptosis: protein–protein interaction and transcriptional regulation they might inhibit mitogenic signal-reducing tumour growth they might make cells less sensitive to apoptosis The final effect would be a consequence of the net balance among alternative signalling pathways and the relative strength of their respective signals high VRK2 levels might be a component in the formation of more indolent and perhaps Cell lines A549 (p53 wt) and H1299 (p53−/−) from lung carcinomas HEK293T cells and HeLa cells were cultured at 37 °C with 5% CO2 in RPMI or DMEM supplemented with 10% heat-inactivated foetal calf serum supplemented with 2 mM L-glutamine 50 μg/ml streptomycin and 100 U/ml penicillin cells were fixed with 4% paraformaldehyde and incubated with propidium iodide Cells were analysed in a FACScalibur flow cytometer data acquisition was performed with Cell Quest programme (Becton Dickinson) analysed with Modfit LT programme (Verity Software House Camptothecin and propidium iodide were from Sigma (St DiOC6(3) (3,3′—Dihexyloxacarbocyanine iodide) was from Molecular Probes (Eugene Annexin V-FITC was from Immunostep (Salamanca,Spain) Total RNA was extracted from A549 cells using RNeasy kit from Qiagen (Valencia The quality of the extracted RNA was determined in a Bioanalyzer 2100 nano-lab chip (Agilent 50 μg of total RNA was amplified with specific primers for Bax The Quantitect-SYBR green RT-PCR kit (Qiagen) was used in an iCycler iQ5 Multicolour Real-time PCR Detection System and Optical System Software BIO-RAD iQ5 (BioRad The following primers were used for RT-PCR amplification Bax was amplified with primers (forward: 5′-GGCCCACCAGCTCTGAGCAGA-3′ Bcl-xL (forward: 5′-TCCTTGTCTACGCTTTCCACG-3′; reverse: 5′-GGTCGCATTGTGGCCTTT-3′) Bcl-2 (forward: 5′-CATGTGTGTGGAGAGCGTCAA-3′ and reverse: 5′-GCCGGTTCAGGTACTCAGTCA-3′) VRK2 (forward: 5′-AGTGAGAGAAGCGCTGAGTCCT-3′ and reverse: 5′-CAAAGGTTCTTGAGACTCTTG-3′) GAPDH (forward: 5′-GGTCTTACTCCTTGGAGGCCATGTG-3′ and reverse: 5′-ACCTAACTACATGGTTTACATGTT-3′) All primers were synthesized by Sigma-Aldrich (St Louis AU1 epitope was detected with monoclonal or polyclonal antibodies from Covance (Emeryville GST was detected with monoclonal B-14 (sc-138 HA epitope was detected with monoclonal (Covance) or polyclonal antibody (eBioscience Flag was detected with polyclonal and monoclonal antibodies from Sigma cytochrome c (7H8.2C12) and PARP (c2-10) were from BD Biosciences (San Jose Cleaved PARP was detected with monoclonal antibody (F21-852) from BD Biosciences Rabbit polyclonal anti-Bax was from Abcam (Cambridge Bcl-2 was detected with sc-492 from Santa Cruz Cytochrome oxidase II was detected with a monoclonal from Invitrogen The secondary antibodies used from Amersham Biosciences (GE Healthcare anti-rabbit-Cy3 (Fluorolink Cy3) and anti-rabbit-Cy2 (Fluorolink Cy2) in immunofluorescence or anti-mouse-HRP or anti-rabbit-HRP for western blots Cells were harvested 48 h post transfection and lysed with a buffer containing 20 mM Tris-HCl pH 7.4 10% (v/v) glycerol and 1% Triton X-100 plus protease inhibitors 50 μg of total protein lysate were analysed in a 10% SDS–polyacrylamide gel GST pulldowns were performed by incubating 1 mg of total cell extract with Glutathione-Sepharose 4B beads (Amersham Biosciences Pharmacia Biotech) for 12 h at 4 °C Sepharose beads were washed three times with lysis buffer and analysed by SDS–PAGE following by western blots with the corresponding antibodies Luminescence in westerns blot was developed with an ECL kit (Amersham Biosciences) Early apoptotic cells present phosphatydilserine on their surface and were detected by flow cytometry of cells labelled with Annexin V-FITC (Immunostep SL A549 and H1299 cells were grown and transfected with siControl or siVRK2 as indicated above and 96 hours later 106 cells were washed in PBS and stained with annexin-V-FITC and propidium iodide in annexin buffer (0,1 M Hepes/NaOH (pH 7.4) 1.4 M NaCl resuspended in 400 μl and analysed by flow cytometry in a FACS Calibur (Becton Dickinson) Colocalization of proteins was performed by immunofluorescence Cells were fixed with 3% paraformaldehyde and stained with specific antibodies against endogenous proteins Nuclei were stained with DAPI (4′,6′-diamidino-2-fenilindol) Immunofluorescences were examined in a confocal Zeiss LSM 510 microscope (Zeiss Germany) and images were analysed with LSM Image Browser software (Zeiss) the cells were transfected with siRNA and treated with camptothecin (5 μM) the culture media was removed and cells were fixed with 4% paraformaldehyde for 15 min washed with cold PBS and treated with 0.2% Triton-X100 for 5 min Cells were blocked for 15 min in incubation buffer (200 mM potassium cacodylate 2.5 mM cobalt hydrochloride) at room temperature The buffer was changed and 5 μl per point were added containing 50 μM fluorescein-12-dUTP Cells were incubated in a humidified atmosphere in the dark for 1 h at 37 °C The reaction was finished by addition of 1 ml 20 × SSC for 15 min and afterwards cells were rinsed in PBS three times The coverslips were treated with antifade and examined in a confocal Zeiss Axioplan2 microscope Images were analysed using the Openlab 4.0.2 program (Improvision cells were treated with 5 μM and collected for analysis at several time points up to 72 h after drug treatment These cells were washed in PBS and collected by centrifugation at 15 000 r.p.m for 10 min The cell pellet was suspended in PBS containing 20 nM DiOC6 and was incubated at 26 °C for 20 min Cells were analysed in a FACS-Calibur (Becton Dickinson) with the Cell Quest and FCS Express V3 programs (De novo software c-Jun N-terminal kinase interacting protein Involvement of the bcl-2 gene in human follicular lymphoma Proapoptotic multidomain Bcl-2/Bax-family proteins: mechanisms The BCL-2 protein family: opposing activities that mediate cell death Apoptosis: controlled demolition at the cellular level Bcl-2 family members: dual regulators of apoptosis and autophagy Mitochondria in apoptosis: bcl-2 family members and mitochondrial dynamics Cytochrome c: functions beyond respiration Human cellular protein VRK2 interacts specifically with Epstein-Barr virus BHRF1 The vaccinia-related kinases phosphorylate the N' terminus of BAF regulating its interaction with DNA and its retention in the nucleus The protein kinase complement of the human genome Emerging biological functions of the vaccinia-related kinase (VRK) family The human vaccinia-related kinase 1 (VRK1) phosphorylates threonine-18 within the mdm-2 binding site of the p53 tumour suppressor protein Characterization of three paralogous members of the Mammalian vaccinia related kinase family Structure of the pseudokinase VRK3 reveals a degraded catalytic site Proteomics identification of nuclear Ran GTPase as an inhibitor of human VRK1 and VRK2 (vaccinia-related kinase) activities Macro Histone H2A1.2 (MacroH2A1) Protein Suppresses Mitotic Kinase VRK1 during Interphase Roles of VRK1 as a new player in the control of biological processes required for cell division Human VRK1 is an early response gene and its loss causes a block in cell cycle progression VRK1 phosphorylates CREB and mediates CCND1 expression Vaccinia-related Kinase 1 (VRK1) is an upstream nucleosomal kinase required for the assembly of 53BP1 foci in response to ionizing radiation-induced DNA damage Plk3 interacts with and specifically phosphorylates VRK1 in Ser342 a downstream target in a pathway that induces Golgi fragmentation c-Jun phosphorylation by the human vaccinia-related kinase 1 (VRK1) and its cooperation with the N-terminal kinase of c-Jun (JNK) Human vaccinia-related kinase 1 (VRK1) activates the ATF2 transcriptional activity by novel phosphorylation on Thr-73 and Ser-62 and cooperates with JNK The subcellular localization of vaccinia-related kinase-2 (VRK2) isoforms determines their different effect on p53 stability in tumour cell lines Substrate profiling of human vaccinia-related kinases identifies coilin as a phosphorylation target with neurological implications Differential inhibitor sensitivity between human kinases VRK1 and VRK2 Vaccinia-related kinase 2 modulates the stress response to hypoxia mediated by TAK1 Modulation of interleukin-1 transcriptional response by the interaction between VRK2 and the JIP1 scaffold protein VRK2 inhibits mitogen-activated protein kinase signaling and inversely correlates with ErbB2 in human breast cancer VRK2 anchors KSR1-MEK1 to endoplasmic reticulum forming a macromolecular complex that compartmentalizes MAPK signaling Expansion and evolution of cell death programmes a p53 and topoisomerase I-binding RING finger protein is a coactivator of p53 in growth suppression induced by DNA damage Phosphorylation of Bax Ser184 by Akt regulates its activity and apoptosis in neutrophils JNK- and p38 kinase-mediated phosphorylation of Bax leads to its activation and mitochondrial translocation and to apoptosis of human hepatoma HepG2 cells Human VRK2 (Vaccinia-related Kinase 2) modulates tumor cell invasion by hyperactivation of NFAT1 and expression of cyclooxygenase-2 NMR solution structure of human vaccinia-related kinase 1 (VRK1) reveals the C-terminal tail essential for its structural stability and autocatalytic activity A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases Proc Natl Acad Sci USA 2007; 104: 20523–20528 Targeting cancer with small molecule kinase inhibitors Targeting the cancer kinome through polypharmacology Insights for the development of specific kinase inhibitors by targeted structural genomics Differential Inhibitor Sensitivity between Human Kinases VRK1 and VRK2 Breast cancer molecular subtypes respond differently to preoperative chemotherapy Nomograms to predict pathologic complete response and metastasis-free survival after preoperative chemotherapy for breast cancer Mitochondrial Hep27 is a c-Myb target gene that inhibits Mdm2 and stabilizes p53 Bcl-X(L) specifically activates Bak to induce swelling and restructuring of the endoplasmic reticulum Tumor suppressor p53 is a direct transcriptional activator of the human bax gene p53 stabilization and accumulation induced by human vaccinia-related kinase 1 Involvement of mitochondria and caspase-3 in ET-18-OCH(3)-induced apoptosis of human leukemic cells Involvement of mitochondria and recruitment of Fas/CD95 signaling in lipid rafts in resveratrol-mediated antimyeloma and antileukemia actions p53 downregulates its activating vaccinia-related kinase 1 Download references have JAE-CSIC-Fondo Social Europeo Predoctoral fellowships TM and SB were funded by CSIC-Banco Santander and Ministerio de Ciencia e Innovación fellowships respectively This work was funded by grants from Ministerio de Ciencia e Innovación (SAF2010-14935 and CSD2007-0017) The protein interactions from this publication have been submitted to the European Bioinformatics Institute-EMBL IMEx (http://www.imexconsortium.org/) consortium through IntAct (pmid 19850723) and assigned the identifier IM-18530 Supplementary Information accompanies this paper on Cell Death and Disease website This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License visit http://creativecommons.org/licenses/by-nc-nd/3.0/ Download citation DOI: https://doi.org/10.1038/cddis.2013.40 Riviera Prep School students donated their artwork to a silent auction benefiting research to combatHuntington’s Disease The silent auction took place during a gala on May 4 at the Palmetto Bay Village Center The following students are pictured with their art: Maya Masucci Promote your 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Call 305.669.7355 or view our Media Kit. Get to know this historic region for Portuguese white wines With the release of the 2022 and 2023 vintages from Portugal’s small but mighty Vinho Verde region, winegrowers across the appellation continue to prove that their lesser-known (but no less tasty) blends of white varietals such as Alvarinho, Arinto and Avesso grapes are worthy of note. Read senior editor Alison Napjus’ tasting report for scores and tasting notes from Vinho Verde’s recently released vintages. 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Susana Rodríguez general director of Pesqueiro Development of the Ministry of the Sea of the Xunta de Galicia; Agustín Pérez and Juan Manuel Gómez major patrons of the fishermen’s guilds of Lira and Cedeira respectively; Emilio Louro (Milucho) manager of the Lyre Brotherhood; Pepe Novo head of marketing of the Cedeira Brotherhood director of the Ashoka-Spain Foundation and Project Director of the Lonxanet Foundation for Sustainable Fishing The added value that the fishmonger of Lonxanet Directo S.L offers is the possibility of having the guarantee of traceability of the fish and seafood that it will offer to the public of Madrid which is characterized by the greatest respect for the biodiversity of the marine environment as well as by the promotion of traditional knowledge and fishing methods respectful of the environment and local cultures With the opening of this direct point of sale in a place like Madrid the aim is to find solutions to the main problem of the artisanal fishing sector Bringing the product of the Galician brotherhoods transmitting at the same time the values of sustainability and responsible fishing This risky but determined bet is intended to guarantee the future of fishing communities it should also be noted that the brotherhoods of Lira and Cedeira have been the first fishermen’s organizations in the entire Spanish State that have opted for the design and creation of two marine reserves of fishing interest in their respective fishing areas with the firm vocation of involving the fishing sector in the sustainability and conservation of the biodiversity of our seas is the location of this house whose distinguishing feature is a T-shaped roof For this work the Valencia practice of Fran Silvestre and Andrés Alfaro Hofmann has been named the 2020 winner in the Architecture section of the German Design Awards The project seeks to obtain the best vistas of the surroundings with a passable roof that serves as a viewing deck The two levels of the 350-square-meter residence adapt to the sloping terrain with a half-buried floor containing a living room there arent any match using your search terms This was how the two teachers from Galicia greeted us as soon as they saw us at the airport Teresa Nuzzo School in Marsa is in its second year of a second Comenius project Having a teacher exchange with Colexio San Andres in Cedeira (Redondela) not only provided us with the opportunity to delve into a different school setting but also to compare it with previous experiences in Scandinavian schools We were given a warm welcome from staff and pupils alike All the pupils were eager to know more about Malta and about their pen friends from our school They bombarded us with never-ending questions making use of audiovisual material which we obtained beforehand from the Department of Information and the Malta Tourism Authority Three 10-year-olds are in charge of putting up a weekly informative radio programme which is aired during break We were guests during that week and we were struck by their sense of independence and responsibility in carrying out such an assignment we were given a copy of the radio programme which we played when we returned to our classes It's difficult not to mention the fact that there were no more than 12 mixed ability pupils in each class thus making it easier for the low achievers to attain more individual attention Teachers work in a much less stressful environment due to the fact that there is no exam-orientated system the headteacher's role in all Spanish schools is not only related to the administration of the school we actually saw the headmaster of Cedeira giving a PE lesson An excursion which we shall always remember was the one to Santiago de Compostela In spite of the bad weather the beauty of its cathedral made our visit worthwhile and unforgettable we visited Vigo's School of Languages and there we also had an appointment with a lecturer who discussed with us certain teaching methods the colourful and lively school environment the Galicians' amiability and gastronomy were all conducive to making our stay at Cedeira's school a truly unforgettable please register for free or log in to your account After hosting two Welsh teachers on a teachers' exchange last December it was Malta's turn once again to organise a project meeting for the three participating countries The three project co-ordinators met at Theresa Nuzzo School between January 16 and 19 to discuss the work to be done in the third year of the Comenius project entitled "This is me.. and what about you?" The three schools will focus on the teaching of Welsh The history of the language and the histories of the three countries will also be dealt with Children will also go into the history of Bedwas School in Wales Cedeira School in Galicia (Spain) and Theresa Nuzzo it is hoped that all children will get to know each other better all three schools are encouraging the children to keep up constant communication through e-mails and traditional letter-writing it is the practice for the three schools to collect the children's letters and send them all together in a pack to each school at the end of each month Theresa Nuzzo School is also trying to promote Malta as a tourist attraction by showing how rich the island's history is an end product of this Comenius project is the production of simple holiday brochures which will eventually be exchanged among the three schools Having all project co-ordinators here in Malta the school showed the foreigners some of the sights such as Valletta with all its treasures of churches Marsaxlokk and its colourful bay and fishing boats and the prehistoric temples of Hagar Qim and Mnajdra What truly impressed the foreign group was the warm welcome and friendliness shown by all the Maltese children Typical local food also played its part on the foreigners' appetite and outlook with regard to establishing Malta as a holiday destination They left Malta with beautiful memories and plans for a future visit with their families and friends in a more relaxed atmosphere away from schools and their continuous commitment please register for free or log in to your account.