Status of the new height system development

This paper presents a proposal for a new numbering of levelling polygons and benchmarks. Furthermore, an accuracy analysis is done with regard to: measured height differences, residuals calculated from differences of the forward and backward runs, residuals from loop closures, and results from network adjustments

Memory formation shaped by astroglia

Astrocytes, the most heterogeneous glial cells in the central nervous system (CNS), execute a multitude of homeostatic functions and contribute to memory formation. Consolidation of synaptic and systemic memory is a prolonged process and hours are required to form long-term memory. In the past, neurons or their parts have been considered to be the exclusive cellular sites of these processes, however, it has now become evident that astrocytes provide an important and essential contribution to memory formation. Astrocytes participate in the morphological remodeling associated with synaptic plasticity, an energy-demanding process that requires mobilization of glycogen, which, in the CNS, is almost exclusively stored in astrocytes. Synaptic remodeling also involves bidirectional astroglial-neuronal communication supported by astroglial receptors and release of gliosignaling molecules. Astroglia exhibit cytoplasmic excitability that engages second messengers, such as Ca(2+), for phasic, and cyclic adenosine monophosphate (cAMP), for tonic signal coordination with neuronal processes. The detection of signals by astrocytes and the release of gliosignaling molecules, in particular by vesicle-based mechanisms, occurs with a significant delay after stimulation, orders of magnitude longer than that present in stimulus–secretion coupling in neurons. These particular arrangements position astrocytes as integrators ideally tuned to support time-dependent memory formation

Analiza stanja pri uvajanju sodobnega višinskega sistema : Status of the new height system development

V prispevku je predstavljen predlog za novo oštevilčevanje nivelmanskih poligonov in reperjev. Obravnavana je tudi analiza natančnosti izmerjenih višinskih razlik, opravljena na podlagi odstopanj obojestransko merjenih višinskih razlik in odstopanj pri zapiranju nivelmanskih zank. Na podlagi izravnave nivelmanske mreže in nivelmanskih poligonov je analizirana tudi natančnost na podlagi popravkov merjenih višinskih razlik in izvedena ocena natančnosti določitve nadmorske višine reperjev ; This paper presents a proposal for a new numbering of levelling polygons and benchmarks. Furthermore, an accuracy analysis is done with regard to: measured height differences, residuals calculated from differences of the forward and backward runs, residuals from loop closures, and results from network adjustments

The uptake, retention and clearance of drug-loaded dendrimer nanoparticles in astrocytes - electrophysiological quantification

Nanoparticle-based drug delivery systems may impose risks to patients due to potential toxicity associated with lack of clearance from cells or prolonged carrier-cell retention. This work evaluates vesicular cell uptake, retention and the possible transfer of endocytosed methylprednisolone-loaded carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles (NPs) into secretory vesicles of rat cultured astrocytes. Cells were incubated with NPs and unitary vesicle fusions/fissions with the plasma membrane were monitored employing high resolution membrane capacitance measurements. In NPs-treated cells the frequency of unitary exocytotic events was significantly increased. The presence of NPs also induce an increase in the size of exocytotic vesicles interacting with the plasma membrane, which exhibit transient fusion with prolonged fusion pore dwell-time. Live-cell confocal imaging revealed that once NPs internalize into endocytotic compartments they remain in the cell for 7 days, although a significant proportion of these merge with secretory vesicles destined for exocytosis. Co-localization studies show the route of clearance of NPs from cells via the exocytotic pathway. These findings bring new insight into the understanding of the intracellular trafficking and biological interactions of drug-loaded dendrimer NPs targeting astrocytes.The study was supported by the Slovenian Research Agency (grants P3 310, J3 6790, J3 7605) and the European Science Foundation COST STSM grant attributed to S.R. Cerqueira. The authors would also like to acknowledge the funds from the Portuguese Foundation for Science and Technology (fellowships to S.R.C. SFRH/BD/48406/2008) and the European Union's Seventh Framework Programme (FP7/2007-2013, grant agreement no. REGPOT-CT2012- 316331-POLARIS). J.M.O. also thanks the FCT for the funds provided under the program Investigador FCT (IF/00423/2012 and IF/01285/2015).info:eu-repo/semantics/publishedVersio

Neurotoxic phospholipase A2 toxicity model : an insight from mammalian cells

The molecular mechanism of action of presynaptically neurotoxic secreted phospholipases A2 (sPLA2s) has not been fully elucidated. We have recently proposed a model to explain one of the hallmarks of their action - the reduction in endocytosis leading to synaptic vesicle depletion in nerve terminals. Our results speak strongly in favor of a mechanism in which both specific protein-protein interactions and enzymatic activity of the neurotoxic sPLA2 ammodytoxin A (AtxA) are necessary for impairment of clathrin-dependent endocytosis in yeast cells. The reduction of endocytosis was strictly dependent on the enzymatic activity of sPLA2s expressed ectopically in our yeast model cells and was not observedwith the catalytically inactive, non-neurotoxic AtxA-homolog, ammodytin L (AtnL). Here weconfirm the validity of the model in mammalian cells also, by demonstrating that the enzymatically active mutant of AtnL, shown to inhibit endocytosis in yeast, acts as a presynaptically neurotoxic sPLA2 at the mammalian neuromuscular junction

Differential cargo mobilisation within Weibel-Palade bodies after transient fusion with the plasma membrane.

Inflammatory chemokines can be selectively released from Weibel-Palade bodies (WPBs) during kiss-and-run exocytosis. Such selectivity may arise from molecular size filtering by the fusion pore, however differential intra-WPB cargo re-mobilisation following fusion-induced structural changes within the WPB may also contribute to this process. To determine whether WPB cargo molecules are differentially re-mobilised, we applied FRAP to residual post-fusion WPB structures formed after transient exocytosis in which some or all of the fluorescent cargo was retained. Transient fusion resulted in WPB collapse from a rod to a spheroid shape accompanied by substantial swelling (>2 times by surface area) and membrane mixing between the WPB and plasma membranes. Post-fusion WPBs supported cumulative WPB exocytosis. To quantify diffusion inside rounded organelles we developed a method of FRAP analysis based on image moments. FRAP analysis showed that von Willebrand factor-EGFP (VWF-EGFP) and the VWF-propolypeptide-EGFP (Pro-EGFP) were immobile in post-fusion WPBs. Because Eotaxin-3-EGFP and ssEGFP (small soluble cargo proteins) were largely depleted from post-fusion WPBs, we studied these molecules in cells preincubated in the weak base NH4Cl which caused WPB alkalinisation and rounding similar to that produced by plasma membrane fusion. In these cells we found a dramatic increase in mobilities of Eotaxin-3-EGFP and ssEGFP that exceeded the resolution of our method (∼ 2.4 µm2/s mean). In contrast, the membrane mobilities of EGFP-CD63 and EGFP-Rab27A in post-fusion WPBs were unchanged, while P-selectin-EGFP acquired mobility. Our data suggest that selective re-mobilisation of chemokines during transient fusion contributes to selective chemokine secretion during transient WPB exocytosis. Selective secretion provides a mechanism to regulate intravascular inflammatory processes with reduced risk of thrombosis

Pennsylvania Folklife Vol. 39, No. 4

• Our Church • Pig Roast • Wooden Jointed Dolls • Coal Jewelry • The Pennsylvania Long Rifle • The Mennonites • Festival Focus • Festival Programs • Blockprinting • Dried Flowers, Wreaths and Baskets • Broom Making • Wood-Turning • Moravian and German Stars • A Plain Costume Primer • Farewell to the Folk Festival Magazinehttps://digitalcommons.ursinus.edu/pafolklifemag/1128/thumbnail.jp

Brain energy metabolism: A roadmap for future research

Although we have learned much about how the brain fuels its functions over the last decades, there remains much still to discover in an organ that is so complex. This article lays out major gaps in our knowledge of interrelationships between brain metabolism and brain function, including biochemical, cellular, and subcellular aspects of functional metabolism and its imaging in adult brain, as well as during development, aging, and disease. The focus is on unknowns in metabolism of major brain substrates and associated transporters, the roles of insulin and of lipid droplets, the emerging role of metabolism in microglia, mysteries about the major brain cofactor and signaling molecule NAD+, as well as unsolved problems underlying brain metabolism in pathologies such as traumatic brain injury, epilepsy, and metabolic downregulation during hibernation. It describes our current level of understanding of these facets of brain energy metabolism as well as a roadmap for future research