The call of ‘thinking wild’ in times of climate disaster: indigenous wisdom from Southern Africa

ASC – Publicaties niet-programma gebonde

Waking up dormant tumors

As appreciation grows for the contribution of the tumor microenvironment to the progression of cancer, new evidence accumulates to support that the participation of stromal cells can extend beyond the local environment. Recently, Elkabets and colleagues demonstrated a systemic interaction between cancer cells and distant bone marrow cells to support the growth of otherwise indolent tumor cells at a secondary site, raising thought-provoking questions regarding the involvement of stromal cells in maintaining metastatic dormancy.National Institutes of Health (U.S.) (NIH grant CA125550)National Institutes of Health (U.S.) (NIH grant CA155370)National Institutes of Health (U.S.) (NIH grant CA151925)National Institutes of Health (U.S.) (NIH grant DK081576)United States. Dept. of Defense (Breast Cancer Research Program Predoctoral Traineeship Award

Linking high-frequency DOC dynamics to the age of connected water sources

Acknowledgments The authors would like to thank our NRI colleagues for all their help with field and laboratory work, especially Audrey Innes, Jonathan Dick, and Ann Porter. We would like to also thank Iain Malcolm (Marine Scotland Science) for providing AWS data and the European Research Council ERC (project GA 335910 VEWA) for funding the VeWa project. Please contact the authors for access to the data used in this paper. We would also like to thank the Natural Environment Research Council NERC (project NE/K000268/1) for funding.Peer reviewedPublisher PD

Potent antitumoral activity of TRAIL through generation of tumor-targeted single-chain fusion proteins

In an attempt to improve TRAIL's (tumor necrosis factor-related apoptosis-inducing ligand) tumor selective activity a variant was designed, in which the three TRAIL protomers are expressed as a single polypeptide chain (scTRAIL). By genetic fusion with a single-chain antibody fragment (scFv) recognizing the extracellular domain of ErbB2, we further equipped scTRAIL with tumor-targeting properties. We studied tumor targeting and apoptosis induction of scFv–scTRAIL in comparison with non-targeted scTRAIL. Importantly, the tumor antigen-targeted scTRAIL fusion protein showed higher apoptotic activity in vitro, with a predominant action by TRAIL-R2 signaling. Pharmacokinetic studies revealed increased plasma half-life of the targeted scTRAIL fusion protein compared with scTRAIL. In vivo studies in a mouse tumor model with xenotransplanted Colo205 cells confirmed greater response to the ErbB2-specific scTRAIL fusion protein compared with non-targeted scTRAIL both under local and systemic application regimen. Together, in vitro and in vivo data give proof of concept of higher therapeutic activity of tumor-targeted scFv–scTRAIL molecules. Further, we envisage that through targeting of scTRAIL, potential side effects should be minimized. We propose that scFv-mediated tumor targeting of single-chain TRAIL represents a promising strategy to improve TRAIL's antitumoral action and to minimize potential unwanted actions on normal tissues

Morphological stasis masks ecologically divergent coral species on tropical reefs

Coral reefs are the epitome of species diversity, yet the number of described scleractinian coral species, the framework-builders of coral reefs, remains moderate by comparison. DNA sequencing studies are rapidly challenging this notion by exposing a wealth of undescribed diversity, but the evolutionary and ecological significance of this diversity remains largely unclear. Here, we present an annotated genome for one of the most ubiquitous corals in the Indo-Pacific (Pachyseris speciosa) and uncover, through a comprehensive genomic and phenotypic assessment, that it comprises morphologically indistinguishable but ecologically divergent lineages. Demographic modeling based on whole-genome resequencing indicated that morphological crypsis (across micro- and macromorphological traits) was due to ancient morphological stasis rather than recent divergence. Although the lineages occur sympatrically across shallow and mesophotic habitats, extensive genotyping using a rapid molecular assay revealed differentiation of their ecological distributions. Leveraging "common garden'' conditions facilitated by the overlapping distributions, we assessed physiological and quantitative skeletal traits and demonstrated concurrent phenotypic differentiation. Lastly, spawning observations of genotyped colonies highlighted the potential role of temporal reproductive isolation in the limited admixture, with consistent genomic signatures in genes related to morphogenesis and reproduction. Overall, our findings demonstrate the presence of ecologically and phenotypically divergent coral species without substantial morphological differentiation and provide new leads into the potential mechanisms facilitating such divergence. More broadly, they indicate that our current taxonomic framework for reef-building corals may be scratching the surface of the ecologically relevant diversity on coral reefs, consequently limiting our ability to protect or restore this diversity effectively

Juxtaposing a cultural reading of landscape with institutional boundaries: the case of the Masebe Nature Reserve, South Africa

The article explores theoretically the juxtaposition of local stories about landscape with institutional arrangements and exclusionary practices around a conservation area in South Africa. The Masebe Nature Reserve is used as a case study. The article argues that the institutional arrangements in which the nature reserve is currently positioned are too static, and consequently exclusionary, in their demarcation of boundaries. This stifles local communities’ sense of belonging to these landscapes. Hence, they strongly resent and feel alienated by the nature reserve. Their opposition and alienation often manifests in poaching. The empirical material is based on how local people living adjacent to the Masebe Nature Reserve have historically named and interpreted the area’s impressive sandstone mountains, in the process creating a sense of belonging. Juxtaposing this mostly tranquil cultural reading of the landscape to the institutional practices of boundary demarcation gives the analysis an immediate critical edge regarding issues of social justic

Electro-oxidation of cyanide on active and non-active anodes: Designing the electrocatalytic response of cobalt spinels

[EN] The feasibility of the electrochemical technologies for wastewater treatment greatly relies on the design of efficient but inexpensive electrocatalysts. It is generally accepted that the so-called ¿non-active¿ anodes (like the boron-doped diamond (BDD) or SnO2-based anodes), producing highly oxidizing hydroxyl radicals, are the most promising candidates for pollutants abatement. In this work, the electrocatalytic performance of various cobalt oxides, pure and doped with Cu or Au, for CN¿ oxidation has been studied and compared with that of conventional graphite, BDD, SnO2-Sb and SnO2-Sb-Pt. The metal oxide electrodes were prepared by thermal decomposition of the salt precursors onto Ti. For the M-doped Co3O4 electrodes, the nominal M/Co ratios were Cu/ Co=0.07¿1.00; and Au/Co=0.05¿0.20. The electrodes were characterized by different techniques (XRD, SEM, EDX, XPS) and their electrocatalytic response was studied by cyclic voltammetry and galvanostatic electrolysis in a H-type cell in aqueous 0.1M NaOH. The obtained results show that the nature of the dopant plays a key role on the electrocatalytic behavior of cobalt spinels. Thus, while Cu catalyzes the CN¿ electro-oxidation, Au declines it. This is explained by the fact that, unlike Au (which segregates as Au-rich particles), Cu is effectively incorporated into the spinel structure by forming a solid solution (CuxCo3-xO4). In this solid solution, atomic scale Cu(spinel)-CN¿ specific interactions occur to catalyze the reaction, whereas in segregated Au particles the oxidation is hindered probably by a too-strong adsorption of cyanide and/or its inaccessibility to oxide active sites. Electrolysis runs have revealed that ¿active¿ over-saturated Cu-doped spinels (Cu/Co=1.00) exhibit higher current efficiencies than conventional graphite and ¿non-active¿ BDD and SnO2-based anodes. Hence, we hereby demonstrate that an inexpensive ¿active¿ electrocatalyst can show even higher efficiency than the most powerful BDD anode. These results highlight the significance of anode design in the application of the electrochemical technique for wastewater treatment.Financial support from the Spanish Ministerio de Economia y Competitividad and FEDER funds (MAT2016-76595-R, IJCI-2014-20012) is gratefully acknowledgedBerenguer, R.; Quijada, C.; La Rosa-Toro, A.; Morallón, E. (2019). Electro-oxidation of cyanide on active and non-active anodes: Designing the electrocatalytic response of cobalt spinels. Separation and Purification Technology. 208:42-50. https://doi.org/10.1016/j.seppur.2018.05.024S425020

Tailoring cells for clinical needs: Meeting report from the Advanced Therapy in Healthcare symposium (October 28–29 2017, Doha, Qatar)

New technologies and therapies designed to facilitate development of personalized treatments are rapidly emerging in the field of biomedicine. Strikingly, the goal of personalized medicine refined the concept of therapy by developing cell-based therapies, the so-called “living drugs”. Breakthrough advancements were achieved in this regard in the fields of gene therapy, cell therapy, tissue-engineered products and advanced therapeutic techniques. The Advanced Therapies in Healthcare symposium, organized by the Clinical Research Center Department of Sidra Medicine, in Doha, Qatar (October 2017), brought together world-renowned experts from the fields of oncology, hematology, immunology, inflammation, autoimmune disorders, and stem cells to offer a comprehensive picture of the status of worldwide advanced therapies in both pre-clinical and clinical development, providing insights to the research phase, clinical data and regulatory aspects of these therapies. Highlights of the meeting are provided in this meeting report

ErbB2 (HER2)-CAR-NK-92 cells for enhanced immunotherapy of metastatic fusion-driven alveolar rhabdomyosarcoma

IntroductionMetastatic rhabdomyosarcoma (RMS) is a challenging tumor entity that evades conventional treatments and endogenous antitumor immune responses, highlighting the need for novel therapeutic strategies. Applying chimeric antigen receptor (CAR) technology to natural killer (NK) cells may offer safe, effective, and affordable therapies that enhance cancer immune surveillance. MethodsHere, we assess the efficacy of clinically usable CAR-engineered NK cell line NK-92/5.28.z against ErbB2-positive RMS in vitro and in a metastatic xenograft mouse model.ResultsOur results show that NK-92/5.28.z cells effectively kill RMS cells in vitro and significantly prolong survival and inhibit tumor progression in mice. The persistence of NK-92/5.28.z cells at tumor sites demonstrates efficient antitumor response, which could help overcome current obstacles in the treatment of solid tumors.DiscussionThese findings encourage further development of NK-92/5.28.z cells as off-the-shelf immunotherapy for the treatment of metastatic RMS