High Blood Flow Into the Femur Indicates Elevated Aerobic Capacity in Synapsids Since the Synapsida-Sauropsida Split

Varanids are the only non-avian sauropsids that are known to approach the warm-blooded mammals in stamina. Furthermore, a much higher maximum metabolic rate (MMR) gives endotherms (including birds) higher stamina than crocodiles, turtles, and non-varanid lepidosaurs. This has led researchers to hypothesize that mammalian endothermy evolved as a second step after the acquisition of elevated MMR in non-mammalian therapsids from a plesiomorphic state of low metabolic rates. In recent amniotes, MMR correlates with the index of blood flow into the femur (Qi), which is calculated from femoral length and the cross-sectional area of the nutrient foramen. Thus, Qi may serve as an indicator of MMR range in extinct animals. Using the Qi proxy and phylogenetic eigenvector maps, here we show that elevated MMRs evolved near the base of Synapsida. Non-mammalian synapsids, including caseids, edaphosaurids, sphenacodontids, dicynodonts, gorgonopsids, and non-mammalian cynodonts, show Qi values in the range of recent endotherms and varanids, suggesting that raised MMRs either evolved in synapsids shortly after the Synapsida-Sauropsida split in the Mississippian or that the low MMR of lepidosaurs and turtles is apomorphic, as has been postulated for crocodiles.Peer Reviewe

Increased large conductance calcium-activated potassium (BK) channel expression accompanied by STREX variant downregulation in the developing mouse CNS

BACKGROUND: Large conductance calcium- and voltage activated potassium (BK) channels are important determinants of neuronal excitability through effects on action potential duration, frequency and synaptic efficacy. The pore- forming subunits are encoded by a single gene, KCNMA1, which undergoes extensive alternative pre mRNA splicing. Different splice variants can confer distinct properties on BK channels. For example, insertion of the 58 amino acid stress-regulated exon (STREX) insert, that is conserved throughout vertebrate evolution, encodes channels with distinct calcium sensitivity and regulation by diverse signalling pathways compared to the insertless (ZERO) variant. Thus, expression of distinct splice variants may allow cells to differentially shape their electrical properties during development. However, whether differential splicing of BK channel variants occurs during development of the mammalian CNS has not been examined. RESULTS: Using quantitative real-time polymerase chain reaction (RT-PCR) Taqman™ assays, we demonstrate that total BK channel transcripts are up regulated throughout the murine CNS during embryonic and postnatal development with regional variation in transcript levels. This upregulation is associated with a decrease in STREX variant mRNA expression and an upregulation in ZERO variant expression. CONCLUSION: As BK channel splice variants encode channels with distinct functional properties the switch in splicing from the STREX phenotype to ZERO phenotype during embryonic and postnatal CNS development may provide a mechanism to allow BK channels to control distinct functions at different times of mammalian brain development

Validating CFD predictions of flow over an escarpment using ground-based and airborne measurement devices

Micrometeorological observations from a tower, an eddy-covariance (EC) station and an unmanned aircraft system (UAS) at the WINSENT test-site are used to validate a computational fluid dynamics (CFD) model, driven by a mesoscale model. The observation site is characterised by a forested escarpment in a complex terrain. A two-day measurement campaign with a flow almost perpendicular to the escarpment is analysed. The first day is dominated by high wind speeds, while, on the second one, calm wind conditions are present. Despite some minor differences, the flow structure, analysed in terms of horizontal wind speeds, wind direction and inclination angles shows similarities for both days. A real-time strategy is used for the CFD validation with the UAS measurement, where the model follows spatially and temporally the aircraft. This strategy has proved to be successful. Stability indices such as the potential temperature and the bulk Richardson number are calculated to diagnose atmospheric boundary layer (ABL) characteristics up to the highest flight level. The calculated bulk Richardson values indicate a dynamically unstable region behind the escarpment and near the ground for both days. At higher altitudes, the ABL is returning to a near neutral state. The same characteristics are found in the model but only for the first day. The second day, where shear instabilities are more dominant, is not well simulated. UAS proves its great value for sensing the flow over complex terrains at high altitudes and we demonstrate the usefulness of UAS for validating and improving models

BMP2-induced chemotaxis requires PI3K p55γ/p110α-dependent phosphatidylinositol (3,4,5)-triphosphate production and LL5β recruitment at the cytocortex

Background: BMP-induced chemotaxis of mesenchymal progenitors is fundamental for vertebrate development, disease and tissue repair. BMP2 induces Smad and non-Smad signalling. Whereas signal transduction via Smads lead to transcriptional responses, non-Smad signalling induces both, transcriptional and immediate/early non-transcriptional responses. However, the molecular mechanisms by which BMP2 facilitates planar cell polarity, cortical actin rearrangements, lamellipodia formation and chemotaxis of mesenchymal progenitors are poorly understood. Our aim was to uncover the molecular mechanism by which BMP2 facilitates chemotaxis via the BMP2-dependent activation of PI3K and spatiotemporal control of PIP3 production important for actin rearrangements at the mesenchymal cell cytocortex. Results: We unveiled the molecular mechanism by which BMP2 induces non-Smad signalling by PI3K and the role of the second messenger PIP3 in BMP2-induced planar cell polarity, cortical actin reorganisation and lamellipodia formation. By using protein interaction studies, we identified the class Ia PI3K regulatory subunit p55γ to act as a specific and non-redundant binding partner for BMP receptor type II (BMPRII) in concert with the catalytic subunit p110α. We mapped the PI3K interaction to a region within the BMPRII kinase. Either BMP2 stimulation or increasing amounts of BMPRI facilitated p55γ association with BMPRII, but BMPRII kinase activity was not required for the interaction. We visualised BMP2-dependent PIP3 production via PI3K p55γ/p110α and were able to localise PIP3 to the leading edge of intact cells during the process of BMP2-induced planar cell polarity and actin dependent lamellipodia formation. Using mass spectrometry, we found the highly PIP3-sensitive PH-domain protein LL5β to act as a novel BMP2 effector in orchestrating cortical actin rearrangements. By use of live cell imaging we found that knock-down of p55γ or LL5β or pharmacological inhibition of PI3K impaired BMP2-induced migratory responses. Conclusions: Our results provide evidence for an important contribution of the BMP2-PI3K (p55γ/p110α)- PIP3-LL5β signalling axis in mesenchymal progenitor cell chemotaxis. We demonstrate molecular insights into BMP2-induced PI3K signalling on the level of actin reorganisation at the leading edge cytocortex. These findings are important to better understand BMP2–induced cytoskeletal reorganisation and chemotaxis of mesenchymal progenitors in different physiological or pathophysiological contexts

Ontogeny of synaptophysin and synaptoporin in the central nervous system

The expression of the synaptic vesicle antigens synaptophysin (SY) and synaptoporin (SO) was studied in the rat striatum, which contains a nearly homogeneous population of GABAergic neurons. In situ hybridization revealed high levels of SY transcripts in the striatal anlage from embryonic day (E) 14 until birth. In contrast. SO hybridization signals were low, and no immunoreactive cell bodies were detected at these stages of development. At E 14, SY-immunoreactivity was restricted to perikarya. In later prenatal stages of development SY-immunoreactivity appeared in puncta (identified as terminals containing immunostained synaptic vesicles), fibers, thick fiber bundles and ‘patches’. In postnatal and adult animals, perikarya of striatal neurons exhibited immunoreaction for SO; ultrastructurally SO antigen was found in the Golgi apparatus and in multivesicular bodies. SO-positive boutons were rare in the striatum. In the neuropil, numerous presynaptic terminals positive for SY were observed. Our data indicate that the expression of synaptic vesicle proteins in GABAergic neurons of the striatum is developmentally regulated. Whereas SY is prevalent during embryonic development, SO is the major synaptic vesicle antigen expressed postnatally by striatal neurons which project to the globus pallidus and the substantia nigra. In contrast synapses of striatal afferents (predominantly from cortex, thalamus and substantia nigra) contain SY

The impact of climate change on incomes and convergence in Africa

© 2019 Elsevier Ltd Climate change is projected to detrimentally affect African countries’ economic development, while income inequalities across economies is among the highest on the planet. However, it is projected that income levels would converge on the continent. Hitherto there is limited evidence on how climate change could affect projected income convergence, accelerating, slowing down, or even reversing this process. Here, we analyze convergence considering climate-change damages, by employing an economic model embedding the three dimensions of risks at the country-level: exposure, vulnerability and hazards. The results show (1) with historical mean climate-induced losses between 10 and 15 percent of GDP per capita growth, the majority of African economies are poorly adapted to their current climatic conditions, (2) Western and Eastern African countries are projected to be the most affected countries on the continent and (3) As a consequence of these heightened impacts on a number of countries, inequalities between countries are projected to widen in the high warming scenario compared to inequalities in the low and without warming scenarios. To mitigate the impacts of economic development and inequalities across countries, we stress (1) the importance of mitigation ambition and Africa's leadership in keeping global mean temperature increase below 1.5 °C, (2) the need to address the current adaptation deficit as soon as possible, (3) the necessity to integrate quantitatively climate risks in economic and development planning and finally (4) we advocate for the generalization of a special treatment for the most vulnerable countries to access climate-related finance. The analysis raises issues on the ability of African countries to reach their SDGs targets and the potential increasing risk of instability, migration across African countries, of decreased trade and economic cooperation opportunities as a consequence of climate change – exacerbating its negative consequences

The impact of climate change on incomes and convergence in Africa

© 2019 Elsevier Ltd Climate change is projected to detrimentally affect African countries’ economic development, while income inequalities across economies is among the highest on the planet. However, it is projected that income levels would converge on the continent. Hitherto there is limited evidence on how climate change could affect projected income convergence, accelerating, slowing down, or even reversing this process. Here, we analyze convergence considering climate-change damages, by employing an economic model embedding the three dimensions of risks at the country-level: exposure, vulnerability and hazards. The results show (1) with historical mean climate-induced losses between 10 and 15 percent of GDP per capita growth, the majority of African economies are poorly adapted to their current climatic conditions, (2) Western and Eastern African countries are projected to be the most affected countries on the continent and (3) As a consequence of these heightened impacts on a number of countries, inequalities between countries are projected to widen in the high warming scenario compared to inequalities in the low and without warming scenarios. To mitigate the impacts of economic development and inequalities across countries, we stress (1) the importance of mitigation ambition and Africa's leadership in keeping global mean temperature increase below 1.5 °C, (2) the need to address the current adaptation deficit as soon as possible, (3) the necessity to integrate quantitatively climate risks in economic and development planning and finally (4) we advocate for the generalization of a special treatment for the most vulnerable countries to access climate-related finance. The analysis raises issues on the ability of African countries to reach their SDGs targets and the potential increasing risk of instability, migration across African countries, of decreased trade and economic cooperation opportunities as a consequence of climate change – exacerbating its negative consequences

Recyclable and Robust Optical Nanoprobes with Engineered Enzymes for Sustainable Serodiagnostics

Recyclable fluorescence assays that can be stored at room temperature would greatly benefit biomedical diagnostics by bringing sustainability and cost-efficiency, especially for point-of-care serodiagnostics in developing regions. Here, a general strategy is proposed to generate recyclable fluorescent probes by using engineered enzymes with enhanced thermo-/chemo-stability, which maintains an outstanding serodiagnostic performance (accuracy >95%) after 10 times of recycling as well as after storage at elevated temperatures (37 °C for 10 days). With these three outstanding properties, recyclable fluorescent probes can be designed to detect various biomarkers of clinical importance by using different enzymes

Odd skipped-related 1 controls the pro-regenerative response of fibro-adipogenic progenitors

Skeletal muscle regeneration requires the coordinated interplay of diverse tissue-resident- and infiltrating cells. Fibro-adipogenic progenitors (FAPs) are an interstitial cell population that provides a beneficial microenvironment for muscle stem cells (MuSCs) during muscle regeneration. Here we show that the transcription factor Osr1 is essential for FAPs to communicate with MuSCs and infiltrating macrophages, thus coordinating muscle regeneration. Conditional inactivation of Osr1 impaired muscle regeneration with reduced myofiber growth and formation of excessive fibrotic tissue with reduced stiffness. Osr1-deficient FAPs acquired a fibrogenic identity with altered matrix secretion and cytokine expression resulting in impaired MuSC viability, expansion and differentiation. Immune cell profiling suggested a novel role for Osr1-FAPs in macrophage polarization. In vitro analysis suggested that increased TGFβ signaling and altered matrix deposition by Osr1-deficient FAPs actively suppressed regenerative myogenesis. In conclusion, we show that Osr1 is central to FAP function orchestrating key regenerative events such as inflammation, matrix secretion and myogenesis