Relief of hypoxia by angiogenesis promotes neural stem cell differentiation by targeting glycolysis

Blood vessels are part of the stem cell niche in the developing cerebral cortex, but their in vivo role in controlling the expansion and differentiation of neural stem cells (NSCs) in development has not been studied. Here, we report that relief of hypoxia in the developing cerebral cortex by ingrowth of blood vessels temporo‐spatially coincided with NSC differentiation. Selective perturbation of brain angiogenesis in vessel‐specific Gpr124 null embryos, which prevented the relief from hypoxia, increased NSC expansion at the expense of differentiation. Conversely, exposure to increased oxygen levels rescued NSC differentiation in Gpr124 null embryos and increased it further in WT embryos, suggesting that niche blood vessels regulate NSC differentiation at least in part by providing oxygen. Consistent herewith, hypoxia‐inducible factor (HIF)‐1α levels controlled the switch of NSC expansion to differentiation. Finally, we provide evidence that high glycolytic activity of NSCs is required to prevent their precocious differentiation in vivo. Thus, blood vessel function is required for efficient NSC differentiation in the developing cerebral cortex by providing oxygen and possibly regulating NSC metabolism.     

The Kinetochore-Microtubule Coupling Machinery Is Repurposed in Sensory Nervous System Morphogenesis

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Global warming promotes biological invasion of a honey bee pest

Climate change and biological invasions are two major global environmental challenges. Both may interact, e.g. via altered impact and distribution of invasive alien species. Even though invasive species play a key role for compromising the health of honey bees, the impact of climate change on the severity of such species is still unknown. The small hive beetle (SHB, Aethina tumida, Murray) is a parasite of honey bee colonies. It is endemic to sub‐Saharan Africa and has established populations on all continents except Antarctica. Since SHBs pupate in soil, pupation performance is governed foremost by two abiotic factors, soil temperature and moisture, which will be affected by climate change. Here, we investigated SHB invasion risk globally under current and future climate scenarios. We modelled survival and development time during pupation (=pupal performance) in response to soil temperature and soil moisture using published and novel experimental data. Presence data on SHB distribution were used for model validation. We then linked the model with global soil data in order to classify areas (resolution: 10 arcmin; i.e. 18.6 km at the equator) as unsuitable, marginal and suitable for SHB pupation performance. Under the current climate, the results show that many areas globally yet uninvaded are actually suitable, suggesting considerable SHB invasion risk. Future scenarios of global warming project a vehement increase in climatic suitability for SHB and corresponding potential for invasion, especially in the temperate regions of the Northern hemisphere, thereby creating demand for enhanced and adapted mitigation and management. Our analysis shows, for the first time, effects of global warming on a honey bee pest and will help areas at risk to prepare adequately. In conclusion, this is a clear case for global warming promoting biological invasion of a pest species with severe potential to harm important pollinator species globally.     

A general framework for propagule dispersal in mangroves

Dispersal allows species to shift their distributions in response to changing climate conditions. As a result, dispersal is considered a key process contributing to a species' long‐term persistence. For many passive dispersers, fluid dynamics of wind and water fuel these movements and different species have developed remarkable adaptations for utilizing this energy to reach and colonize suitable habitats. The seafaring propagules (fruits and seeds) of mangroves represent an excellent example of such passive dispersal. Mangroves are halophytic woody plants that grow in the intertidal zones along tropical and subtropical shorelines and produce hydrochorous propagules with high dispersal potential. This results in exceptionally large coastal ranges across vast expanses of ocean and allows species to shift geographically and track the conditions to which they are adapted. This is particularly relevant given the challenges presented by rapid sea‐level rise, higher frequency and intensity of storms, and changes in regional precipitation and temperature regimes. However, despite its importance, the underlying drivers of mangrove dispersal have typically been studied in isolation, and a conceptual synthesis of mangrove oceanic dispersal across spatial scales is lacking. Here, we review current knowledge on mangrove propagule dispersal across the various stages of the dispersal process. Using a general framework, we outline the mechanisms and ecological processes that are known to modulate the spatial patterns of mangrove dispersal. We show that important dispersal factors remain understudied and that adequate empirical data on the determinants of dispersal are missing for most mangrove species. This review particularly aims to provide a baseline for developing future research agendas and field campaigns, filling current knowledge gaps and increasing our understanding of the processes that shape global mangrove distributions.     

Comparison of quasisteady-state performance of the DEAMOX process under intermittent and continuous feeding and different nitrogen loading rates

The recently developed denitrifying ammonium oxidation (DEAMOX) process combines the anammox reaction with autotrophic denitrifying conditions using sulfide as an electron donor for the production of nitrite from nitrate within an anaerobic biofilm. This paper compares a quasisteady-state performance of this process for treatment of baker's yeast wastewater under intermittent and continuous feeding and increasing nitrogen loading rate (NLR) from 300 till 858 mg N/L/d. The average total nitrogen removal slightly decreased on increasing the NLR: from 86 to 79% (intermittent feeding) and from 87 to 84% (continuous feeding). The better performance under continuous feeding was due to a more complete nitrate removal in the former case whereas the ammonia removal was similar for both feeding regimes under the comparable NLR. A possible explanation can be that, during continuous feeding (simultaneous supply of nitrate and sulfide), there were less mass transfer limitations for sulfide oxidizing denitrifiers presumably located in the outer layer of sludge aggregates. On the contrary, the ammonia oxidisers presumably located inside the aggregates apparently suffered from nitrite mass transfer limitations under both the feedings. The paper further describes some characteristics of the DEAMOX sludge.     

Outmigration pathways of stocked juvenile European sturgeon (Acipenser sturio L., 1758) in the Lower Rhine River,as revealed by telemetry

Working towards a future Rhine Sturgeon Action Plan the outmigration pathways of stocked juvenile European sturgeon (Acipenser sturio L., 1758) were studied in the River Rhine in 2012 and 2015 using the NEDAP Trail system. A total of 87 sturgeon of 3 to 5 years old (n = 43 in 2012, n = 44 in 2015) were implanted with transponders and released in May and June in the river Rhine at the Dutch‐German border, approximately 160 km from the sea. In total three sturgeons (3%) were found dead on river banks within seven days after the release. Based upon their wounds these sturgeons were likely hit by ship‐propellers. Tracking results were obtained from 57 (66%) of the sturgeons, of which 39 (45%) indicated movement into the Port of Rotterdam. Here the sturgeons remained for an average of two weeks, which suggests they spent time to acclimatize to higher salinities before entering the North Sea. Of the 45 (52%) sturgeons that were confirmed to have entered the North Sea, ten (22%) were recaptured (mainly by shrimpers and gill‐nets) close to the Dutch coastline; nine were alive and were released. From the results we obtained the preferred outmigration pathways, movement speeds and an indication of impacting factors (i.e. ship propellers and bycatch). Bycatches provided also localisations information in the coastal area. A next step to complete this work would be to assess habitat selection in freshwater and downstream migration of young of the year (YOY sturgeons) in the Lower Rhine.     

Gestational jet lag predisposes to later-life skeletal and cardiac disease

Circadian rhythm disturbance (CRD) increases the risk of disease, e.g. metabolic syndrome, cardiovascular disease, and cancer. In the present study, we investigated later life adverse health effects triggered by repeated jet lag during gestation. Pregnant mice were subjected to a regular light-dark cycle (CTRL) or to a repeated delay (DEL) or advance (ADV) jet lag protocol. Both DEL and ADV offspring showed reduced weight gain. ADV offspring had an increased circadian period, and an altered response to a jet lag was observed in both DEL and ADV offspring. Analysis of the bones of adult male ADV offspring revealed reduced cortical bone mass and strength. Strikingly, analysis of the heart identified structural abnormalities and impaired heart function. Finally, DNA methylation analysis revealed hypermethylation of miR17-92 cluster and differential methylation within circadian clock genes, which correlated with altered gene expression. We show that developmental CRD affects the circadian system and predisposes to non-communicable disease in adult life.     

E2a/Pbx1 induces the rapid proliferation of stem cell factor-dependent murine pro-T cells that cause acute T-lymphoid or myeloid leukemias in mice

Oncoprotein E2a/Pbx1 is produced by the t(1;19) chromosomal translocation of human pre-B acute lymphoblastic leukemia. E2a/Pbx1 blocks differentiation of primary myeloid progenitors but, paradoxically, induces apoptosis in established pre-B-cell lines, and no transforming function of E2a/Pbx1 has been reported in cultured lymphoid progenitors. Here, we demonstrate that E2a/Pbx1 induces immortal proliferation of stem cell factor (SCF)-dependent pro-T thymocytes by a mechanism dependent upon both its transactivation and DNA-binding functions. E2a-Pbx1 cooperated with cytokines or activated signaling oncoproteins to induce cell division, as inactivation of conditional E2a/Pbx1 in either factor-dependent pro-T cells or pro-T cells made factor independent by expression of Bcr/Abl resulted in pro-T-cell quiescence, while reactivation of E2a/Pbx1 restored cell division. Infusion of E2a/Pbx1 pro-T cells in mice caused T lymphoblastic leukemia and, unexpectedly, acute myeloid leukemia. The acute lymphoblastic leukemia did not evidence further maturation, suggesting that E2a/Pbx1 establishes an early block in pro-T-cell development that cannot be overcome by marrow or thymic microenvironments. In an E2a/Pbx1 pro-T thymocyte clone that induced only pro-T acute lymphoblastic leukemia, coexpression of Bcr/Abl expanded its leukemic phenotype to include acute myeloid leukemia, suggesting that unique functions of cooperating signaling oncoproteins can influence the lymphoid versus myeloid character of E2a/Pbx1 leukemia and may cooperate with E2a/Pbx1 to dictate the pre-B-cell phenotype of human leukemia containing t(1;19).     

An induced Ets repressor complex regulates growth arrest during terminal macrophage differentiation

Defining the molecular mechanisms that coordinately regulate proliferation and differentiation is a central issue in development. Here, we describe a mechanism in which induction of the Ets repressor METS/PE1 links terminal differentiation to cell cycle arrest. Using macrophages as a model, we provide evidence that METS/PE1 blocks Ras-dependent proliferation without inhibiting Ras-dependent expression of cell type-specific genes by selectively replacing Ets activators on the promoters of cell cycle control genes. Antiproliferative effects of METS require its interaction with DP103, a DEAD box-containing protein that assembles a novel corepressor complex. Functional interactions between the METS/DP103 complex and E2F/ pRB family proteins are also necessary for inhibition of cellular proliferation, suggesting a combinatorial code that directs permanent cell cycle exit during terminal differentiation.