Kanstruphalberg0865

Adapting to climate change and sea level rise is challenging on small islands. False adaptation can lead to adverse impacts on natural and societal dynamics. Therefore, an interdisciplinary perspective on the interaction of natural dynamics, societal demands, and political decisions is crucial. buy GF109203X In this sense, this study scrutinizes coastal processes and socio-political dimensions of erosion on the reef island Fuvahmulah, the Maldives. The national government and Fuvahmulah's population have an opposed perception and attribution of the drivers and processes behind Fuvahmulah's most pressing coastal issue - coastal erosion. To review these perceptions, natural dynamics are recreated with process-based methods and discussed regarding present and projected marine pressures. Population surveys and interviews with actors in coastal development complement the physical insights into erosion on Fuvahmulah and describe the socio-political dimension of climate change adaptation on small islands. This interdisciplinary approach demonstrates how small-islands' adaptive capacities are typically impaired and disclose the potential of local knowledge to overcome maldevelopment.Photophysical and photochemical properties of graphene quantum dots (GQDs) strongly depend on their morphological and chemical features. However, systematic and uniform manipulation of the chemical structures of GQDs remains challenging due to the difficulty in simultaneous control of competitive reactions, i.e., growth and doping, and the complicated post-purification processes. Here, we report an efficient and scalable production of chemically tailored N-doped GQDs (NGs) with high uniformity and crystallinity via a simple one-step solvent catalytic reaction for the thermolytic self-assembly of molecular precursors. We find that the graphitization of N-containing precursors during the formation of NGs can be modulated by intermolecular interaction with solvent molecules, the mechanism of wh ich is evidenced by theoretical calculations and various spectroscopic analyses. Given with the excellent visible-light photoresponse and photocatalytic activity of NGs, it is expected that the proposed approach will promote the practical utilization of GQDs for various applications in the near future.Hydroalkylation, the direct addition of a C(sp3)-H bond across an olefin, is a desirable strategy to produce valuable, complex structural motifs in functional materials, pharmaceuticals, and natural products. Herein, we report a reliable method for accessing α-branched amines via nickel-catalyzed hydroalkylation reactions. Specifically, by using bis(cyclooctadiene)nickel (Ni(cod)2) together with a phosphine ligand, we achieved a formal C(sp3)-H bond insertion reaction between olefins and N-sulfonyl amines without the need for an external hydride source. The amine not only provides the alkyl motif but also delivers hydride to the olefin by means of a nickel-engaged β-hydride elimination/reductive elimination process. This method provides a platform for constructing chiral α-branched amines by using a P-chiral ligand, demonstrating its potential utility in organic synthesis. Notably, a sulfonamidyl boronate complex formed in situ under basic conditions promotes ring-opening of the azanickellacycle reaction intermediate, leading to a significant improvement of the catalytic efficiency.Many neuron types consist of populations with continuously varying molecular properties. Here, we show a continuum of postsynaptic molecular properties in three types of neurons and assess the functional correlates in cerebellar unipolar brush cells (UBCs). While UBCs are generally thought to form discrete functional subtypes, with mossy fiber (MF) activation increasing firing in ON-UBCs and suppressing firing in OFF-UBCs, recent work also points to a heterogeneity of response profiles. Indeed, we find a continuum of response profiles that reflect the graded and inversely correlated expression of excitatory mGluR1 and inhibitory mGluR2/3 pathways. MFs coactivate mGluR2/3 and mGluR1 in many UBCs, leading to sequential inhibition-excitation because mGluR2/3-currents are faster. Additionally, we show that DAG-kinase controls mGluR1 response duration, and that graded DAG kinase levels correlate with systematic variation of response duration over two orders of magnitude. These results demonstrate that continuous variations in metabotropic signaling can generate a stable cell-autonomous basis for temporal integration and learning over multiple time scales.Phospholipase D3 (PLD3) and PLD4 polymorphisms have been associated with several important inflammatory diseases. Here, we show that PLD3 and PLD4 digest ssRNA in addition to ssDNA as reported previously. Moreover, Pld3-/-Pld4-/- mice accumulate small ssRNAs and develop spontaneous fatal hemophagocytic lymphohistiocytosis (HLH) characterized by inflammatory liver damage and overproduction of Interferon (IFN)-γ. Pathology is rescued in Unc93b13d/3dPld3-/-Pld4-/- mice, which lack all endosomal TLR signaling; genetic codeficiency or antibody blockade of TLR9 or TLR7 ameliorates disease less effectively, suggesting that both RNA and DNA sensing by TLRs contributes to inflammation. IFN-γ made a minor contribution to pathology. Elevated type I IFN and some other remaining perturbations in Unc93b13d/3dPld3-/-Pld4-/- mice requires STING (Tmem173). Our results show that PLD3 and PLD4 regulate both endosomal TLR and cytoplasmic/STING nucleic acid sensing pathways and have implications for the treatment of nucleic acid-driven inflammatory disease.The deglacial hydroclimate in South China remains a long-standing topic of debate due to the lack of reliable moisture proxies and inconsistent model simulations. A recent hydroclimate proxy suggests that South China became wet in cold stadials during the last deglaciation, with the intensification proposed to be contributed mostly by the East Asian summer monsoon (EASM). Here, based on a deglacial simulation in a state-of-the-art climate model that well reproduces the evolution of EASM, winter monsoon (EAWM) and the associated water isotopes in East Asia, we propose that the intensified hydroclimate in South China is also contributed heavily by the rainfall in autumn, during the transition between EASM and EAWM. The excessive rainfall in autumn results from the convergence between anomalous northerly wind due to amplified land-sea thermal contrast and anomalous southerly wind associated with the anticyclone over Western North Pacific, both of which are, in turn, forced by the slowdown of the Atlantic thermohaline circulation. Regardless the rainfall change, however, the modeled δ18Op remains largely unchanged in autumn. Our results provide new insights to East Asia monsoon associated with climate change in the North Atlantic.TRIP6, a member of the ZYXIN-family of LIM domain proteins, is a focal adhesion component. Trip6 deletion in the mouse, reported here, reveals a function in the brain ependymal and choroid plexus epithelial cells are carrying, unexpectedly, fewer and shorter cilia, are poorly differentiated, and the mice develop hydrocephalus. TRIP6 carries numerous protein interaction domains and its functions require homodimerization. Indeed, TRIP6 disruption in vitro (in a choroid plexus epithelial cell line), via RNAi or inhibition of its homodimerization, confirms its function in ciliogenesis. Using super-resolution microscopy, we demonstrate TRIP6 localization at the pericentriolar material and along the ciliary axoneme. The requirement for homodimerization which doubles its interaction sites, its punctate localization along the axoneme, and its co-localization with other cilia components suggest a scaffold/co-transporter function for TRIP6 in cilia. Thus, this work uncovers an essential role of a LIM-domain protein assembly factor in mammalian ciliogenesis.Tumor organoids offer new opportunities for translational cancer research, but unlike animal models, their broader use is hindered by the lack of clinically relevant imaging endpoints. Here, we present a positron-emission microscopy method for imaging clinical radiotracers in patient-derived tumor organoids with spatial resolution 100-fold better than clinical positron emission tomography (PET). Using this method, we quantify 18F-fluorodeoxyglucose influx to show that patient-derived tumor organoids recapitulate the glycolytic activity of the tumor of origin, and thus, could be used to predict therapeutic response in vitro. Similarly, we measure sodium-iodine symporter activity using 99mTc- pertechnetate and find that the iodine uptake pathway is functionally conserved in organoids derived from thyroid carcinomas. In conclusion, organoids can be imaged using clinical radiotracers, which opens new possibilities for identifying promising drug candidates and radiotracers, personalizing treatment regimens, and incorporating clinical imaging biomarkers in organoid-based co-clinical trials.Optogenetics combined with electrical recording has emerged as a powerful tool for investigating causal relationships between neural circuit activity and function. However, the size of optogenetically manipulated tissue is typically 1-2 orders of magnitude larger than that can be electrically recorded, rendering difficulty for assigning functional roles of recorded neurons. Here we report a viral vector-delivery optrode (VVD-optrode) system for precise integration of optogenetics and electrophysiology in the brain. Our system consists of flexible microelectrode filaments and fiber optics that are simultaneously self-assembled in a nanoliter-scale, viral vector-delivery polymer carrier. The highly localized delivery and neuronal expression of opsin genes at microelectrode-tissue interfaces ensure high spatial congruence between optogenetically manipulated and electrically recorded neuronal populations. We demonstrate that this multifunctional system is capable of optogenetic manipulation and electrical recording of spatially defined neuronal populations for three months, allowing precise and long-term studies of neural circuit functions.Organization of the genome into transcriptionally active euchromatin and silenced heterochromatin is essential for eukaryotic cell function. Phase-separation has been implicated in heterochromatin formation, but it is unclear how phase-separated condensates can contribute to stable repression, particularly for heritable epigenetic changes. Polycomb complex PRC1 is key for heterochromatin formation, but the multitude of Polycomb proteins has hindered our understanding of their collective contribution to chromatin repression. Here, we show that PRC1 forms multicomponent condensates through hetero-oligomerization. They preferentially seed at H3K27me3 marks, and subsequently write H2AK119Ub marks. We show that inducing Polycomb phase-separation can cause chromatin compaction, but polycomb condensates are dispensable for maintenance of the compacted state. Our data and simulations are consistent with a model in which the time integral of Polycomb phase-separation is progressively recorded in repressive histone marks, which subsequently drive compaction. These findings link the equilibrium thermodynamics of phase-separation with the fundamentally non-equilibrium concept of epigenetic memory.