Arctic megaslide at presumed rest

Published version. Source at http://doi.org/10.1038/srep38529. License CC BY 4.0.Slope failure like in the Hinlopen/Yermak Megaslide is one of the major geohazards in a changing Arctic environment. We analysed hydroacoustic and 2D high-resolution seismic data from the apparently intact continental slope immediately north of the Hinlopen/Yermak Megaslide for signs of past and future instabilities. Our new bathymetry and seismic data show clear evidence for incipient slope instability. Minor slide deposits and an internally-deformed sedimentary layer near the base of the gas hydrate stability zone imply an incomplete failure event, most probably about 30000 years ago, contemporaneous to or shortly after the Hinlopen/Yermak Megaslide. An active gas reservoir at the base of the gas hydrate stability zone demonstrate that over-pressured fluids might have played a key role in the initiation of slope failure at the studied slope, but more importantly also for the giant HYM slope failure. To date, it is not clear, if the studied slope is fully preconditioned to fail completely in future or if it might be slowly deforming and creeping at present. We detected widespread methane seepage on the adjacent shallow shelf areas not sealed by gas hydrates

Safety and feasibility of third-party multipotent adult progenitor cells for immunomodulation therapy after liver transplantation--a phase I study (MISOT-I)

BACKGROUND: Liver transplantation is the definitive treatment for many end-stage liver diseases. However, the life-long immunosuppression needed to prevent graft rejection causes clinically significant side effects. Cellular immunomodulatory therapies may allow the dose of immunosuppressive drugs to be reduced. In the current protocol, we propose to complement immunosuppressive pharmacotherapy with third-party multipotent adult progenitor cells (MAPCs), a culture-selected population of adult adherent stem cells derived from bone marrow that has been shown to display potent immunomodulatory and regenerative properties. In animal models, MAPCs reduce the need for pharmacological immunosuppression after experimental solid organ transplantation and regenerate damaged organs. METHODS: Patients enrolled in this phase I, single-arm, single-center safety and feasibility study (n=3-24) will receive 2 doses of third-party MAPCs after liver transplantation, on days 1 and 3, in addition to a calcineurin-inhibitor-free "bottom-up" immunosuppressive regimen with Basiliximab, mycophenolic acid, and steroids. The study objective is to evaluate the safety and clinical feasibility of MAPC administration in this patient cohort. The primary endpoint of the study is safety, assessed by standardized dose-limiting toxicity events. One secondary endpoint is the time until first biopsy-proven acute rejection, in order to collect first evidence of efficacy. Dose escalation (150, 300, 450, and 600 million MAPCs) will be done according to a 3 + 3 classical escalation design (4 groups of 3-6 patients each). DISCUSSION: If MAPCs are safe for patients undergoing liver transplantation in this study, a phase II/III trial will be conducted to assess their clinical efficacy

Mesenchymal stem cells are short-lived and do not migrate beyond the lungs after intravenous infusion

Mesenchymal stem cells (MSC) are under investigation as a therapy for a variety of disorders. Although animal models show long term regenerative and immunomodulatory effects of MSC, the fate of MSC after infusion remains to be elucidated. In the present study the localization and viability of MSC was examined by isolation and re-culture of intravenously infused MSC. C57BL/6 MSC (500,000) constitutively expressing DsRed-fluorescent protein and radioactively labeled with Cr-51 were infused via the tail vein in wild-type C57BL/6 mice. After 5 min, 1, 24, or 72 h, mice were sacrificed and blood, lungs, liver, spleen, kidneys, and bone marrow removed. One hour after MSC infusion the majority of Cr-51 was found in the lungs, whereas after 24 h Cr-51 was mainly found in the liver. Tissue cultures demonstrated that viable donor MSC were present in the lungs up to 24 h after infusion, after which they disappeared. No viable MSC were found in the other organs examined at any time. The induction of ischemia-reperfusion injury in the liver did not trigger the migration of viable MSC to the liver. These results demonstrate that MSC are short-lived after i.v. infusion and that viable MSC do not pass the lungs. Cell debris may be transported to the liver. Long term immunomodulatory and regenerative effects of infused MSC must therefore be mediated via other cell types

An exploration of social determinants of health amongst internally displaced persons in northern Uganda

Social determinants of health describe the conditions in which people are born, grow, live, work and age and their influence on health. These circumstances are shaped by the distribution of money, power and resources at global, national and local levels, which are themselves influenced by policy choices. Armed conflict and forced displacement are important influences on the social determinants of health. There is limited evidence on the social determinants of health of internally displaced persons (IDPs) who have been forced from their homes due to armed conflict but remain within the borders of their country. The aim of this study was to explore the social determinants of overall physical and mental health of IDPs, including the response strategies used by IDPs to support their health needs. Northern Uganda was chosen as a case-study, and 21 face-to-face semi-structured interviews with IDPs were conducted in fifteen IDP camps between November and December 2006

Subcellular localization defines modification and production of Δ-tetrahydrocannabinolic acid synthase in transiently transformed Nicotiana benthamiana.

OBJECTIVE Through heterologous expression of the tetrahydrocannabinolic acid synthase (THCAS) coding sequence from Cannabis sativa L. in Nicotiana benthamiana, we evaluated a transient plant-based expression system for the production of enzymes involved in cannabinoid biosynthesis. RESULTS Thcas was modularized according to the GoldenBraid grammar and its expression tested upon alternative subcellular localization of the encoded catalyst with and without fusion to a fluorescent protein. THCAS was detected only when ER targeting was used; cytosolic and plastidal localization resulted in no detectable protein. Moreover, THCAS seems to be glycosylated in N. benthamiana, suggesting that this modification might have an influence on the stability of the protein. Activity assays with cannabigerolic acid as a substrate showed that the recombinant enzyme produced not only THCA (123 ± 12 fkat g activity towards THCA production) but also cannabichromenic acid (CBCA; 31 ± 2.6 fkat g activity towards CBCA production). CONCLUSION Nicotiana benthamiana is a suitable host for the generation of cannabinoid producing enzymes. To attain whole pathway integration, careful analysis of subcellular localization is necessary

Public support for global vaccine sharing in the COVID-19 pandemic: Evidence from Germany.

By September 2021 an estimated 32% of the global population was fully vaccinated for COVID-19 but the global distribution of vaccines was extremely unequal, with 72% or more vaccinated in the ten countries with the highest vaccination rates and less than 2% in the ten countries with the lowest vaccination rates. Given that governments need to secure public support for investments in global vaccine sharing, it is important to understand the levels and drivers of public support for international vaccine solidarity. Using a factorial experiment administered to more than 10,000 online survey respondents in Germany in 2021, we demonstrate that the majority of German citizens are against global inequalities in vaccine distribution. Respondents are supportive of substantive funding amounts, on the order of the most generous contributions provided to date, though still below amounts that are likely needed for a successful global campaign. Public preferences appear largely to be driven by intrinsic concern for the welfare of global populations though are in part explained by material considerations-particularly risks of continued health threats from a failure to vaccinate globally. Strategic considerations are of more limited importance in shaping public opinion; in particular we see no evidence for free riding on contributions by other states. Finally, drawing on an additional survey experiment, we show that there is scope to use information campaigns highlighting international health externalities to augment public support for global campaigns

Submarine slope failures due to pipe structure formation

There is a strong correlation between submarine slope failures and the occurrence of gas hydrates. Here, the authors use a combination of seismic data and numerical modelling to show that overpressure at the gas hydrate stability zone leads to potential destabilization of the slope and submarine landslides

Marginal effects of conditions.

Marginal effects of conditions.</p