Synaptotagmin-7 Is an Asynchronous Calcium Sensor for Synaptic Transmission in Neurons Expressing SNAP-23

Synchronization of neurotransmitter release with the presynaptic action potential is essential for maintaining fidelity of information transfer in the central nervous system. However, synchronous release is frequently accompanied by an asynchronous release component that builds up during repetitive stimulation, and can even play a dominant role in some synapses. Here, we show that substitution of SNAP-23 for SNAP-25 in mouse autaptic glutamatergic hippocampal neurons results in asynchronous release and a higher frequency of spontaneous release events (mEPSCs). Use of neurons from double-knock-out (SNAP-25, synaptotagmin-7) mice in combination with viral transduction showed that SNAP-23-driven release is triggered by endogenous synaptotagmin-7. In the absence of synaptotagmin-7 release became even more asynchronous, and the spontaneous release rate increased even more, indicating that synaptotagmin-7 acts to synchronize release and suppress spontaneous release. However, compared to synaptotagmin-1, synaptotagmin-7 is a both leaky and asynchronous calcium sensor. In the presence of SNAP-25, consequences of the elimination of synaptotagmin-7 were small or absent, indicating that the protein pairs SNAP-25/synaptotagmin-1 and SNAP-23/synaptotagmin-7 might act as mutually exclusive calcium sensors. Expression of fusion proteins between pHluorin (pH-sensitive GFP) and synaptotagmin-1 or -7 showed that vesicles that fuse using the SNAP-23/synaptotagmin-7 combination contained synaptotagmin-1, while synaptotagmin-7 barely displayed activity-dependent trafficking between vesicle and plasma membrane, implying that it acts as a plasma membrane calcium sensor. Overall, these findings support the idea of alternative syt∶SNARE combinations driving release with different kinetics and fidelity

Assessment of aerosol–cloud–radiation correlations in satellite observations, climate models and reanalysis

Representing large-scale co-variability between variables related to aerosols, clouds and radiation is one of many aspects of agreement with observations desirable for a climate model. In this study such relations are investigated in terms of temporal correlations on monthly mean scale, to identify points of agreement and disagreement with observations. Ten regions with different meteorological characteristics and aerosol signatures are studied and correlation matrices for the selected regions offer an overview of model ability to represent present day climate variability. Global climate models with different levels of detail and sophistication in their representation of aerosols and clouds are compared with satellite observations and reanalysis assimilating meteorological fields as well as aerosol optical depth from observations. One example of how the correlation comparison can guide model evaluation and development is the often studied relation between cloud droplet number and water content. Reanalysis, with no parameterized aerosol–cloud coupling, shows weaker correlations than observations, indicating that microphysical couplings between cloud droplet number and water content are not negligible for the co-variations emerging on larger scale. These observed correlations are, however, not in agreement with those expected from dominance of the underlying microphysical aerosol–cloud couplings. For instance, negative correlations in subtropical stratocumulus regions show that suppression of precipitation and subsequent increase in water content due to aerosol is not a dominating process on this scale. Only in one of the studied models are cloud dynamics able to overcome the parameterized dependence of rain formation on droplet number concentration, and negative correlations in the stratocumulus regions are reproduced

The BAH domain of Rsc2 is a histone H3 binding domain

Bromo-adjacent homology (BAH) domains are commonly found in chromatin-associated proteins and fall into two classes; Remodels the Structure of Chromatin (RSC)-like or Sir3-like. Although Sir3-like BAH domains bind nucleosomes, the binding partners of RSC-like BAH domains are currently unknown. The Rsc2 subunit of the RSC chromatin remodeling complex contains an RSC-like BAH domain and, like the Sir3-like BAH domains, we find Rsc2 BAH also interacts with nucleosomes. However, unlike Sir3-like BAH domains, we find that Rsc2 BAH can bind to recombinant purified H3 in vitro, suggesting that the mechanism of nucleosome binding is not conserved. To gain insight into the Rsc2 BAH domain, we determined its crystal structure at 2.4 Å resolution. We find that it differs substantially from Sir3-like BAH domains and lacks the motifs in these domains known to be critical for making contacts with histones. We then go on to identify a novel motif in Rsc2 BAH that is critical for efficient H3 binding in vitro and show that mutation of this motif results in defective Rsc2 function in vivo. Moreover, we find this interaction is conserved across Rsc2-related proteins. These data uncover a binding target of the Rsc2 family of BAH domains and identify a novel motif that mediates this interaction

SNFing HIV transcription

The SWI/SNF chromatin remodeling complex is an essential regulator of transcription of cellular genes. HIV-1 infection induces exit of a core component of SWI/SNF, Ini1, into the cytoplasm and its association with the viral pre-integration complex. Several recent papers published in EMBO Journal, Journal of Biological Chemistry, and Retrovirology provide new information regarding possible functions of Ini1 and SWI/SNF in HIV life cycle. It appears that Ini1 has an inhibitory effect on pre-integration steps of HIV replication, but also contributes to stimulation of Tat-mediated transcription. This stimulation involves displacement of the nucleosome positioned at the HIV promoter

Science verification of the new FlashCam-based camera in the 28m telescope of H.E.S.S

In October 2019 the central 28m telescope of the H.E.S.S. experiment has beenupgraded with a new camera. The camera is based on the FlashCam design whichhas been developed in view of a possible future implementation in themedium-sized telescopes of the Cherenkov Telescope Array (CTA). We report hereon the results of the science verification program that has been performedafter commissioning of the new camera, to show that the camera and softwarepipelines are working up to expectations.<br

Improved limits on dark matter annihilation in the Sun with the 79-string IceCube detector and implications for supersymmetry

We present an improved event-level likelihood formalism for including neutrino telescope data in global fits to new physics. We derive limits on spin-dependent dark matter-proton scattering by employing the new formalism in a re-analysis of data from the 79-string IceCube search for dark matter annihilation in the Sun, including explicit energy information for each event. The new analysis excludes a number of models in the weak-scale minimal supersymmetric standard model (MSSM) for the first time. This work is accompanied by the public release of the 79-string IceCube data, as well as an associated computer code for applying the new likelihood to arbitrary dark matter models.Comment: 24 pages, 8 figs, 1 table. Contact authors: Pat Scott & Matthias Danninger. Likelihood tool available at http://nulike.hepforge.org. v2: small updates to address JCAP referee repor

An All-Sky Search for Three Flavors of Neutrinos from Gamma-Ray Bursts with the IceCube Neutrino Observatory

We present the results and methodology of a search for neutrinos produced in the decay of charged pions created in interactions between protons and gamma-rays during the prompt emission of 807 gamma-ray bursts (GRBs) over the entire sky. This three-year search is the first in IceCube for shower-like Cherenkov light patterns from electron, muon, and tau neutrinos correlated with GRBs. We detect five low-significance events correlated with five GRBs. These events are consistent with the background expectation from atmospheric muons and neutrinos. The results of this search in combination with those of IceCube's four years of searches for track-like Cherenkov light patterns from muon neutrinos correlated with Northern-Hemisphere GRBs produce limits that tightly constrain current models of neutrino and ultra high energy cosmic ray production in GRB fireballs.Comment: 33 pages, 14 figures; minor changes made to match published version in the Astrophysical Journal, 2016 June 2