Bacterial porin disrupts mitochondrial membrane potential and sensitizes host cells to apoptosis

The bacterial PorB porin, an ATP-binding beta-barrel protein of pathogenic Neisseria gonorrhoeae, triggers host cell apoptosis by an unknown mechanism. PorB is targeted to and imported by host cell mitochondria, causing the breakdown of the mitochondrial membrane potential (delta psi m). Here, we show that PorB induces the condensation of the mitochondrial matrix and the loss of cristae structures, sensitizing cells to the induction of apoptosis via signaling pathways activated by BH3-only proteins. PorB is imported into mitochondria through the general translocase TOM but, unexpectedly, is not recognized by the SAM sorting machinery, usually required for the assembly of beta-barrel proteins in the mitochondrial outer membrane. PorB integrates into the mitochondrial inner membrane, leading to the breakdown of delta psi m. The PorB channel is regulated by nucleotides and an isogenic PorB mutant defective in ATP-binding failed to induce delta psi m loss and apoptosis, demonstrating that dissipation of delta psi m is a requirement for cell death caused by neisserial infection

Diversity of Staphylococcus aureus Isolates in European Wildlife

Staphylococcus aureus is a well-known colonizer and cause of infection among animals and it has been described from numerous domestic and wild animal species. The aim of the present study was to investigate the molecular epidemiology of S. aureus in a convenience sample of European wildlife and to review what previously has been observed in the subject field. 124 S. aureus isolates were collected from wildlife in Germany, Austria and Sweden; they were characterized by DNA microarray hybridization and, for isolates with novel hybridization patterns, by multilocus sequence typing (MLST). The isolates were assigned to 29 clonal complexes and singleton sequence types (CC1, CC5, CC6, CC7, CC8, CC9, CC12, CC15, CC22, CC25, CC30, CC49, CC59, CC88, CC97, CC130, CC133, CC398, ST425, CC599, CC692, CC707, ST890, CC1956, ST2425, CC2671, ST2691, CC2767 and ST2963), some of which (ST2425, ST2691, ST2963) were not described previously. Resistance rates in wildlife strains were rather low and mecA-MRSA isolates were rare (n = 6). mecC-MRSA (n = 8) were identified from a fox, a fallow deer, hares and hedgehogs. The common cattle- associated lineages CC479 and CC705 were not detected in wildlife in the present study while, in contrast, a third common cattle lineage, CC97, was found to be common among cervids. No Staphylococcus argenteus or Staphylococcus schweitzeri-like isolates were found. Systematic studies are required to monitor the possible transmission of human- and livestock- associated S. aureus/MRSA to wildlife and vice versa as well as the possible transmission, by unprotected contact to animals. The prevalence of S. aureus/MRSA in wildlife as well as its population structures in different wildlife host species warrants further investigation

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities.</p

State of the climate in 2018

In 2018, the dominant greenhouse gases released into Earth’s atmosphere—carbon dioxide, methane, and nitrous oxide—continued their increase. The annual global average carbon dioxide concentration at Earth’s surface was 407.4 ± 0.1 ppm, the highest in the modern instrumental record and in ice core records dating back 800 000 years. Combined, greenhouse gases and several halogenated gases contribute just over 3 W m−2 to radiative forcing and represent a nearly 43% increase since 1990. Carbon dioxide is responsible for about 65% of this radiative forcing. With a weak La Niña in early 2018 transitioning to a weak El Niño by the year’s end, the global surface (land and ocean) temperature was the fourth highest on record, with only 2015 through 2017 being warmer. Several European countries reported record high annual temperatures. There were also more high, and fewer low, temperature extremes than in nearly all of the 68-year extremes record. Madagascar recorded a record daily temperature of 40.5°C in Morondava in March, while South Korea set its record high of 41.0°C in August in Hongcheon. Nawabshah, Pakistan, recorded its highest temperature of 50.2°C, which may be a new daily world record for April. Globally, the annual lower troposphere temperature was third to seventh highest, depending on the dataset analyzed. The lower stratospheric temperature was approximately fifth lowest. The 2018 Arctic land surface temperature was 1.2°C above the 1981–2010 average, tying for third highest in the 118-year record, following 2016 and 2017. June’s Arctic snow cover extent was almost half of what it was 35 years ago. Across Greenland, however, regional summer temperatures were generally below or near average. Additionally, a satellite survey of 47 glaciers in Greenland indicated a net increase in area for the first time since records began in 1999. Increasing permafrost temperatures were reported at most observation sites in the Arctic, with the overall increase of 0.1°–0.2°C between 2017 and 2018 being comparable to the highest rate of warming ever observed in the region. On 17 March, Arctic sea ice extent marked the second smallest annual maximum in the 38-year record, larger than only 2017. The minimum extent in 2018 was reached on 19 September and again on 23 September, tying 2008 and 2010 for the sixth lowest extent on record. The 23 September date tied 1997 as the latest sea ice minimum date on record. First-year ice now dominates the ice cover, comprising 77% of the March 2018 ice pack compared to 55% during the 1980s. Because thinner, younger ice is more vulnerable to melting out in summer, this shift in sea ice age has contributed to the decreasing trend in minimum ice extent. Regionally, Bering Sea ice extent was at record lows for almost the entire 2017/18 ice season. For the Antarctic continent as a whole, 2018 was warmer than average. On the highest points of the Antarctic Plateau, the automatic weather station Relay (74°S) broke or tied six monthly temperature records throughout the year, with August breaking its record by nearly 8°C. However, cool conditions in the western Bellingshausen Sea and Amundsen Sea sector contributed to a low melt season overall for 2017/18. High SSTs contributed to low summer sea ice extent in the Ross and Weddell Seas in 2018, underpinning the second lowest Antarctic summer minimum sea ice extent on record. Despite conducive conditions for its formation, the ozone hole at its maximum extent in September was near the 2000–18 mean, likely due to an ongoing slow decline in stratospheric chlorine monoxide concentration. Across the oceans, globally averaged SST decreased slightly since the record El Niño year of 2016 but was still far above the climatological mean. On average, SST is increasing at a rate of 0.10° ± 0.01°C decade−1 since 1950. The warming appeared largest in the tropical Indian Ocean and smallest in the North Pacific. The deeper ocean continues to warm year after year. For the seventh consecutive year, global annual mean sea level became the highest in the 26-year record, rising to 81 mm above the 1993 average. As anticipated in a warming climate, the hydrological cycle over the ocean is accelerating: dry regions are becoming drier and wet regions rainier. Closer to the equator, 95 named tropical storms were observed during 2018, well above the 1981–2010 average of 82. Eleven tropical cyclones reached Saffir–Simpson scale Category 5 intensity. North Atlantic Major Hurricane Michael’s landfall intensity of 140 kt was the fourth strongest for any continental U.S. hurricane landfall in the 168-year record. Michael caused more than 30 fatalities and $25 billion (U.S. dollars) in damages. In the western North Pacific, Super Typhoon Mangkhut led to 160 fatalities and$6 billion (U.S. dollars) in damages across the Philippines, Hong Kong, Macau, mainland China, Guam, and the Northern Mariana Islands. Tropical Storm Son-Tinh was responsible for 170 fatalities in Vietnam and Laos. Nearly all the islands of Micronesia experienced at least moderate impacts from various tropical cyclones. Across land, many areas around the globe received copious precipitation, notable at different time scales. Rodrigues and Réunion Island near southern Africa each reported their third wettest year on record. In Hawaii, 1262 mm precipitation at Waipā Gardens (Kauai) on 14–15 April set a new U.S. record for 24-h precipitation. In Brazil, the city of Belo Horizonte received nearly 75 mm of rain in just 20 minutes, nearly half its monthly average. Globally, fire activity during 2018 was the lowest since the start of the record in 1997, with a combined burned area of about 500 million hectares. This reinforced the long-term downward trend in fire emissions driven by changes in land use in frequently burning savannas. However, wildfires burned 3.5 million hectares across the United States, well above the 2000–10 average of 2.7 million hectares. Combined, U.S. wildfire damages for the 2017 and 2018 wildfire seasons exceeded $40 billion (U.S. dollars)

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Verstoord lichaamsbeeld: een cultuurhistorische vergelijking tussen de glasziekte en de morfodysfore stoornis

Achtergrond: Er is in de literatuur over morfodysforie al uitgebreid onderzoek gedaan naar de invloed van heersende schoonheidsidealen op het lichaamsbeeld vanuit de psychologie, sociologie en filosofie, maar nog niet naar de vraag hoe de stoornis volgens de genoemde zienswijzen cultuurhistorisch en technologisch wordt ‘gemedieerd’. Doel: Betogen dat de heersende normen en waarden rondom het uiterlijk die voorschrijven hoe lichaam en geest zich tot elkaar moeten verhouden, in verschillende tijdsperioden door het gebruik van de op dat moment in zwang zijnde technologieën, invloed hebben op de totstandkoming of het verloop van de stoornis. Methode: Literatuurstudie. Resultaten: Een cultuurhistorische vergelijking tussen de glasziekte en de morfodysfore stoornis. Conclusie: Het voert te ver om te zeggen dat de glasziekte van toen de morfodysforie van nu is als we kijken naar het type patiënten of hun symptomen. Echter, als we de relaties vergelijken tussen de notie van een verstoord lichaamsbeeld, en de technologische mediatie van de heersende normen en waarden rondom het perfecte lichaam, kunnen we toch stellen dat beide ziektes gemeenschappelijke kenmerken vertonen. LinkedIn: https://www.linkedin.com/in/elkemuller

Duidelijk Duindorp: Publiek leren in een stadslab

In dit rapport treft u de resultaten aan van ons stadslab in de Haagse wijk Duindorp. In dit stadslab staat het samen leren en proberen met burgers, professionals en ambtenaren in de wijk centraal (publiek leren). De betrokken onderzoekers hebben publieke dialogen georganiseerd en actie / onderzoek uitgevoerd rondom drie prangende lokale kwesties: wonen, veiligheid en (ver)gunnen. Voor het vinden van een betere omgang met deze omstreden vraagstukken is er gelijktijdig gewerkt aan het organiseren van kennis, lokale betrokkenheid en bestuurlijk draagvlak. De onderzoekers, docenten en studenten hebben hiervoor een sterk lokaal en stedelijke netwerk opgezet met bewoners, gemeenteambtenaren en medewerkers van verschillende maatschappelijke instellingen. Deze rapportage beschrijft de gekozen aanpak, de uitkomsten en de doorwerking ervan in het beleid, het onderwijs en in de wijk. Het stadslab Duindorp geeft een goed beeld van de wijze waarop wij als netwerkhogeschool met zowel onderwijs als onderzoek willen en kunnen bijdragen aan de ontwikkeling van de stad Den Haag, de regio en de wijken

Lang lere de netwerksamenleving!: Long live (and learn) the Network Society!

Onderzoeksplatform ‘Connected Learning: ’Al ruim vijftien jaar houdt De Haagse Hogeschool zich bezig met onderzoek als deel van haar missie. Terwijl onderwijs vaak geworteld is in monodisciplinaire vakgebieden, kan met onderzoek wat makkelijker gekeken worden naar domeinen in de samenleving (zorg, veiligheid, ondernemen, etc.) waarin complexe problematiek steeds vaker wél dan niet een multidisciplinaire aanpak vereist. Bijna niemand werkt nog alleen of met alleen vakgenoten aan problemen of uitdagingen. En die veranderende beroepspraktijk is bij uitstek het domein van het hoger beroepsonderwijs. Daar leiden we voor op. Het onderzoeken van en experimenteren met nieuwe uitdagingen in de praktijk verbindt ons sterker met de samenleving, het stelt ons in staat om ons beroepsonderwijs te vernieuwen en geeft docenten, onderzoekers en studenten de kans om zich te ontwikkelen door samen te werken aan vragen en uitdagingen die de toekomst van de beroepspraktijk vorm geven. Veel onderzoek wordt uitgevoerd onder begeleiding van lectoren die samenwerken met docent-onderzoekers, studenten, en professionals in het werkveld aan veelal meerjarige onderzoeksagenda’s die lijn aanbrengen in verschillende deelactiviteiten. Een van de manieren waarop De Haagse Hogeschool onderzoek organiseert is in de vorm van onderzoeksplatforms die zich richten op verschillende domeinen van de samenleving. Wij zijn ‘Connected Learning’, een onderzoeksplatform dat zich richt op leren in de netwerksamenleving - in de samenleving zelf, maar ook in de beroepspraktijk en in ons onderwijs. Aangenaam. Wat wij doen? Daar gaat dit boek over, dus daar verklappen we hier nog niets over. Wat verwacht u als u nadenkt over onze naam? Enig idee? Geen idee? Benieuwd? Lees verder om te ontdekken wat ons inspireert, uitdaagt en nieuwsgierig maakt. Sommige van onze ideeën zijn doordacht en doorleefd omdat we er al jaren onderzoek naar doen, andere zijn nieuw en dagen ons uit om er grip op te krijgen. Wij geven met dit boek een beeld van waar we staan in 2018. Zie het als een eerste kennismaking, met de nadruk op ‘eerste’: we werken graag met veel en verschillende partners. Zie het als visitekaartje van onze onderzoeksagenda. We hopen van harte dat u zich als lezer uitgenodigd voelt om met ons samen op zoek te gaan—misschien wel naar een gezamenlijke toekomst. ‘Connected Learning’ Research Platform: For over fifteen years, The Hague University of Applied Sciences has been carrying out research as part of its mission. While education is often rooted in monodisciplinary subject areas, research allows for a broader look at areas of society (care, security, entrepreneurship etc.), where complex problems more often than not require a multidisciplinary approach. Today, barely anyone works on problems or challenges alone or solely with colleagues from within the same subject area. Universities of applied sciences are uniquely placed to deal with these changes in professional practices; after all, we train the professionals who will one day enter that field. Researching and experimenting with new challenges in professional practice allows us to connect more strongly with society, enables us to be innovative in our professional training and gives lecturers, researchers and students the opportunity to develop themselves by cooperating on the challenges and issues that will shape the future of that professional practice. Most research is carried out under the guidance of professors who cooperate with lecturers/researchers, students and the professional field, mainly on long-term research agendas that provide an outline for various sub-activities. One of the ways in which research is organised at The Hague University of Applied Sciences is in the form of research platforms that focus on various areas of society. We are ‘Connected Learning’, a research platform focusing on learning in the network society — in that society as such, but also in professional practice and our education. Nice to meet you! So, what do we do? That’s what this book is about, so we’re not going to give anything away just yet. Just thinking about our name, what do you expect we do? Any ideas? Or not a clue at all? If you’d like to find out, keep reading to find out what inspires us, what challenges we face and what drives our curiosity. Some of our ideas are well-established because we’ve been researching them for years, while other, newer ideas are more challenging to grasp. This book provides an overview of where we stand in 2018. You could see it as an initial introduction, with the emphasis on “initial”; we work with many different partners, and we enjoy doing so. Alternatively, you could see it as a calling card for our research agenda. We sincerely hope that, as a reader, you feel encouraged to join us in our quest — possibly towards a joint future