Key climate change stressors of marine ecosystems along the path of the east african coastal current

For the countries bordering the tropical Western Indian Ocean (TWIO), living marine resources are vital for food security. However, this region has largely escaped the attention of studies investigating potential impacts of future climate change on the marine environment. Understanding how marine ecosystems in coastal East Africa may respond to various climatic stressors is vital for the development of conservation and other ocean management policies that can help to adapt to climate change impacts on natural and associated human systems. Here, we use a high-resolution (1/4°) ocean model, run under a high emission scenario (RCP 8.5) until the end of the 21st century, to identify key regionally important climate change stressors over the East African Coastal Current (EACC) that flows along the coasts of Kenya and Tanzania. We also discuss these stressors in the context of projections from lower resolution CMIP5 models. Our results indicate that the main drivers of dynamics and the associated ecosystem response in the TWIO are different between the two monsoon seasons. Our high resolution model projects weakening of the Northeast monsoon (December–February) winds and slight strengthening of the Southeast monsoon (May–September) winds throughout the course of the 21st century, consistent with CMIP5 models. The projected shallower mixed layers and weaker upwelling during the Northeast Monsoon considerably reduce the availability of surface nutrients and primary production. Meanwhile, primary production during the Southeast monsoon is projected to be relatively stable until the end of the century. In parallel, a widespread warming of up to 5 °C is projected year-round with extreme events such as marine heatwaves becoming more intense and prolonged, with the first year-long event projected to occur as early as the 2030s. This extreme warming will have significant consequences for both marine ecosystems and the coastal populations dependent on these marine resources. These region-specific stressors highlight the importance of dynamic ocean features such as the upwelling systems associated with key ocean currents. This indicates the need to develop and implement a regional system that monitors the anomalous behaviour of such regionally important features. Additionally, this study draws attention to the importance of investment in decadal prediction methods, including high resolution modelling, that can provide information at time and space scales that are more directly relevant to regional management and policy making

A Major Ecosystem Shift in Coastal East African Waters During the 1997/98 Super El Niño as Detected Using Remote Sensing Data

Under the impact of natural and anthropogenic climate variability, upwelling systems are known to change their properties leading to associated regime shifts in marine ecosystems. These often impact commercial fisheries and societies dependent on them. In a region where in situ hydrographic and biological marine data are scarce, this study uses a combination of remote sensing and ocean modelling to show how a stable seasonal upwelling off the Kenyan coast shifted into the territorial waters of neighboring Tanzania under the influence of the unique 1997/98 El Niño and positive Indian Ocean Dipole event. The formation of an anticyclonic gyre adjacent to the Kenyan/Tanzanian coast led to a reorganization of the surface currents and caused the southward migration of the Somali–Zanzibar confluence zone and is attributed to anomalous wind stress curl over the central Indian Ocean. This caused the lowest observed chlorophyll-a over the North Kenya banks (Kenya), while it reached its historical maximum off Dar Es Salaam (Tanzanian waters). We demonstrate that this situation is specific to the 1997/98 El Niño when compared with other the super El-Niño events of 1972,73, 1982–83 and 2015–16. Despite the lack of available fishery data in the region, the local ecosystem changes that the shift of this upwelling may have caused are discussed based on the literature. The likely negative impacts on local fish stocks in Kenya, affecting fishers’ livelihoods and food security, and the temporary increase in pelagic fishery species’ productivity in Tanzania are highlighted. Finally, we discuss how satellite observations may assist fisheries management bodies to anticipate low productivity periods, and mitigate their potentially negative economic impacts

A HIF-independent, CD133-mediated mechanism of cisplatin resistance in glioblastoma cells

Purpose Glioblastoma Multiforme (GBM) is the commonest brain tumour in adults. A population of cells, known as cancer stem cells (CSCs), is thought to mediate chemo/radiotherapy resistance. CD133 is a cell surface marker to identify and isolate CSCs. However, its functional significance and the relevant microenvironment in which to study CD133 remain unknown. We examined the influence of hypoxia on CD133 expression and the potential functional significance of CD133 in glioblastoma chemoresistance. Methods Gene expression was analysed by qRT-PCR. siRNA technique was used to downregulate genes and confirmed by flow cytometry. IC50 values was evaluated with the Alamar blue assay. Results CD133 expression was upregulated in hypoxia in 2D and 3D models. There was increased resistance to chemotherapeutics, cisplatin, temozolomide and etoposide, in cells cultured in hypoxia compared to normoxia. siRNA knockdown of either HIF1a or HIF2a resulted in reduced CD133 mRNA expression with HIF2a having a more prolonged effect on CD133 expression. HIF2a downregulation sensitized GBM cells to cisplatin to a greater extent than HIF1a but CD133 knockdown had a much more marked effect on cisplatin sensitisation than knockdown of either of the HIFs suggesting a HIF-independent mechanism of cisplatin resistance mediated via CD133. The same mechanism was not involved in temozolomide resistance since downregulation of HIF1a but not HIF2a or CD133 sensitized GBM cells to temozolomide. Conclusion Knowledge of the mechanisms involved in the novel hypoxia-induced CD133-mediated resistance to cisplatin observed might lead to identification of new strategies that enable more effective use of current therapeutic agents

A functional SNP in the regulatory region of the decay-accelerating factor gene associates with extraocular muscle pareses in myasthenia gravis

Complement activation in myasthenia gravis (MG) may damage muscle endplate and complement regulatory proteins such as decay-accelerating factor (DAF) or CD55 may be protective. We hypothesize that the increased prevalence of severe extraocular muscle (EOM) dysfunction among African MG subjects reported earlier may result from altered DAF expression. To test this hypothesis, we screened the DAF gene sequences relevant to the classical complement pathway and found an association between myasthenics with EOM paresis and the DAF regulatory region c.-198C>G SNP (odds ratio=8.6; P=0.0003). This single nucleotide polymorphism (SNP) results in a twofold activation of a DAF 5′-flanking region luciferase reporter transfected into three different cell lines. Direct matching of the surrounding SNP sequence within the DAF regulatory region with the known transcription factor-binding sites suggests a loss of an Sp1-binding site. This was supported by the observation that the c.-198C>G SNP did not show the normal lipopolysaccharide-induced DAF transcriptional upregulation in lymphoblasts from four patients. Our findings suggest that at critical periods during autoimmune MG, this SNP may result in inadequate DAF upregulation with consequent complement-mediated EOM damage. Susceptible individuals may benefit from anti-complement therapy in addition to immunosuppression

Glioma Through the Looking GLASS: Molecular Evolution of Diffuse Gliomas and the Glioma Longitudinal AnalySiS Consortium

Adult diffuse gliomas are a diverse group of brain neoplasms that inflict a high emotional toll on patients and their families. The Cancer Genome Atlas (TCGA) and similar projects have provided a comprehensive understanding of the somatic alterations and molecular subtypes of glioma at diagnosis. However, gliomas undergo significant cellular and molecular evolution during disease progression. We review the current knowledge on the genomic and epigenetic abnormalities in primary tumors and after disease recurrence, highlight the gaps in the literature, and elaborate on the need for a new multi-institutional effort to bridge these knowledge gaps and how the Glioma Longitudinal AnalySiS Consortium (GLASS) aims to systemically catalog the longitudinal changes in gliomas. The GLASS initiative will provide essential insights into the evolution of glioma toward a lethal phenotype, with the potential to reveal targetable vulnerabilities, and ultimately, improved outcomes for a patient population in need

Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: a retrospective multicohort analysis

PURPOSE: Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known. METHODS: Four independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses. RESULTS: Molecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation. CONCLUSION: The most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence

Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis

Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known