Summary (149 words of referenced text): 46The climate impact of aerosols is highly uncertain owing primarily to their poorly quantified 47 influence on cloud properties. During 2014-15, a fissure eruption in Holuhraun (Iceland) 48 emitted huge quantities of sulphur dioxide, resulting in significant reductions in liquid cloud 49 droplet size. Using satellite observations and detailed modelling, we estimate a global mean 50 radiative forcing from the resulting aerosol-induced cloud brightening for the time of the 51 eruption of around -0.2 W.m -2 . Changes in cloud amount or liquid water path are 52 undetectable, indicating that these aerosol-cloud indirect effects are modest. It supports the 53 idea that cloud systems are well buffered against aerosol changes as only impacts on cloud 54 effective radius appear relevant from a climate perspective, thus providing a strong constraint 55 on aerosol-cloud interactions. This result will reduce uncertainties in future climate 56 projections as we are able to reject the results from climate models with an excessive liquid 57 water path response. 58 59Main Text: (3103 words of referenced text, including concluding paragraph) 60 The 2014-15 eruption at Holuhraun (486 words of referenced text): 61Anthropogenic emissions that affect climate are not just confined to greenhouse gases. 62Sulphur dioxide and other pollutants form atmospheric aerosols that can scatter and absorb 63 sunlight and can influence the properties of clouds, modulating the Earth-atmosphere energy 64 balance. Aerosols act as cloud condensation nuclei (CCN); an increase in CCN translates into 65 a higher number of smaller, more reflective cloud droplets that scatter more sunlight back to 66 space 1 (the ÔfirstÕ indirect effect of aerosols). Smaller cloud droplets decrease the efficiency 67 of collision-coalescence processes that are pivotal in rain initiation, thus aerosol-influenced 68 clouds may retain more liquid water and extend coverage/lifetime 2,3 (the ÔsecondÕ or Ôcloud 69 lifetimeÕ indirect effect). Aerosols usually co-vary with key environmental variables making 70 it difficult to disentangle aerosol-cloud impacts from meteorological variability [4][5][6] . 71Additionally, clouds themselves are complex transient systems subject to dynamical 72 feedbacks (e.g. cloud top entrainment/evaporation, invigoration of convection) which 73 influence cloud response [7][8][9][10][11][12] . These aspects present great challenges in evaluating and 74 constraining aerosol-cloud interactions (ACI) in General Circulation Models (GCM) 13-17 , 75 with particular contentious debate surrounding the relative importance of these feedback 76 mechanisms. 77Nonetheless, anthropogenic aerosol emissions are thought to cool the Earth via indirect 78 effects 17 , but the uncertainty ranges from -1.2 to -0.0 W.m -2 (90% confidence interval) due to 79 i) a lack of characterization of the pre-industrial aerosol state 15,18,19 , and ii) model parametric 80 and structural errors in representing cloud responses to aerosol chan...

[1] Absorbing aerosols such as smoke strongly absorb solar radiation, particularly at ultraviolet and visible/near-infrared (VIS/NIR) wavelengths, and their presence above clouds can have considerable implications. It has been previously shown that they have a positive (i.e., warming) direct aerosol radiative effect (DARE) when overlying bright clouds. Additionally, they can cause biased passive instrument satellite retrievals in techniques that rely on VIS/NIR wavelengths for inferring the cloud optical thickness (COT) and effective radius (r e ) of underlying clouds, which can in turn yield biased above-cloud DARE estimates. Here we investigate Moderate Resolution Imaging Spectroradiometer (MODIS) cloud optical property retrieval biases due to overlying absorbing aerosols observed by Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) and examine the impact of these biases on above-cloud DARE estimates. The investigation focuses on a region in the southeast Atlantic Ocean during August and September (2006-2011), where smoke from biomass burning in southern Africa overlies persistent marine boundary layer stratocumulus clouds. Adjusting for above-cloud aerosol attenuation yields increases in the regional mean liquid COT (averaged over all ocean-only liquid clouds) by roughly 6%; mean r e increases by roughly 2.6%, almost exclusively due to the COT adjustment in the non-orthogonal retrieval space. It is found that these two biases lead to an underestimate of DARE. For liquid cloud Aqua MODIS pixels with CALIOP-observed above-cloud smoke, the regional mean above-cloud radiative forcing efficiency (DARE per unit aerosol optical depth (AOD)) at time of observation (near local noon for Aqua overpass) increases from 50.9WmÀ2 AOD À1 to 65.1Wm À2 AOD À1 when using bias-adjusted instead of nonadjusted MODIS cloud retrievals.Citation: Meyer, K., S. Platnick, L. Oreopoulos, and D. Lee (2013), Estimating the direct radiative effect of absorbing aerosols overlying marine boundary layer clouds in the southeast Atlantic using MODIS and CALIOP,

Shank3 is a postsynaptic scaffolding protein implicated in synapse development and autism spectrum disorders. The Shank3 gene is known to produce diverse splice variants whose functions have not been fully explored. In the present study, we generated mice lacking Shank3 exon 9 (Shank3Δ9 mice), and thus missing five out of 10 known Shank3 splice variants containing the N-terminal ankyrin repeat region, including the longest splice variant, Shank3a. Our X-gal staining results revealed that Shank3 proteins encoded by exon 9-containing splice variants are abundant in upper cortical layers, striatum, hippocampus, and thalamus, but not in the olfactory bulb or cerebellum, despite the significant Shank3 mRNA levels in these regions. The hippocampal CA1 region of Shank3Δ9 mice exhibited reduced excitatory transmission at Schaffer collateral synapses and increased frequency of spontaneous inhibitory synaptic events in pyramidal neurons. In contrast, prelimbic layer 2/3 pyramidal neurons in the medial prefrontal cortex displayed decreased frequency of spontaneous inhibitory synaptic events, indicating alterations in the ratio of excitation/inhibition (E/I ratio) in the Shank3Δ9 brain. These mice displayed a mild increase in rearing in a novel environment and mildly impaired spatial memory, but showed normal social interaction and repetitive behavior. These results suggest that ankyrin repeat-containing Shank3 splice variants are important for E/I balance, rearing behavior, and spatial memory.

The MAM domain-containing GPI anchor proteins MDGA1 and MDGA2 are Ig superfamily adhesion molecules composed of six IG domains, a fibronectin III domain, a MAM domain, and a GPI anchor. MDGAs contribute to the radial migration and positioning of a subset of cortical neurons during early neural development. However, MDGAs continue to be expressed in postnatal brain, and their functions during postnatal neural development remain unknown. Here, we demonstrate that MDGAs specifically and with a nanomolar affinity bind to neuroligin-2, a cell-adhesion molecule of inhibitory synapses, but do not bind detectably to neuroligin-1 or neuroligin-3. We observed no cell adhesion between cells expressing neuroligin-2 and MDGA1, suggesting a cis interaction. Importantly, RNAi-mediated knockdown of MDGAs increased the abundance of inhibitory but not excitatory synapses in a neuroligin-2-dependent manner. Conversely, overexpression of MDGA1 decreased the numbers of functional inhibitory synapses. Likewise, coexpression of both MDGA1 and neuroligin-2 reduced the synaptogenic capacity of neuroligin-2 in an artificial synapse-formation assay by abolishing the ability of neuroligin-2 to form an adhesion complex with neurexins. Taken together, our data suggest that MDGAs inhibit the activity of neuroligin-2 in controlling the function of inhibitory synapses and that MDGAs do so by binding to neuroligin-2.inhibitory synapse formation | synaptic cell adhesion | autism | schizophrenia R ecent studies of synapse formation have uncovered a multitude of synaptic adhesion molecules, and human genetic studies have implicated many of these molecules in neuropsychiatric and neurodevelopmental disorders (1-4). However, little is known about the specific pathophysiological mechanisms by which dysfunctions of synaptic adhesion molecules contribute to these complex disorders.Neurexins and neuroligins (NLs) are arguably the most extensively studied synaptic adhesion molecules (1). They are dispensable for initial synapse establishment but act in an isoformdependent manner to specify the maturation of either excitatory or inhibitory synapses (5). There are four NL members in rodents (NL1-NL4) that show distinct synaptic localizations and functions (5). NL2, in particular, has received considerable attention because of its unique localization and function at inhibitory synapses (6). For instance, NL2 controls perisomatic inhibitory synapse maturation together with gephyrin and collybistin, which regulate GABA receptor clustering on neurons (7,8). Moreover, NL2 exhibits differential functions at different types of inhibitory synapses on the same postsynaptic neuron (9). All four NLs likely mediate synapse-promoting activities through direct interactions with presynaptic neurexins, but NLs also perform additional functions in synapse validation that are independent of their binding to neurexins (10).MAM domain-containing GPI anchor proteins (MDGAs), also termed "GPIMs" or "MAMDCs," initially were identified in tumor cells (11). The two homologous MDGA ...

We update previously published MODIS global cloud regimes (CRs) using the latest MODIS cloud retrievals in the Collection 6 dataset. We implement a slightly different derivation method, investigate the composition of the regimes, and then proceed to examine several aspects of CR radiative appearance with the aid of various radiative flux datasets. Our results clearly show the CRs are radiatively distinct in terms of shortwave, longwave and their combined (total) cloud radiative effect. We show that we can clearly distinguish regimes based on whether they radiatively cool or warm the atmosphere, and thanks to radiative heating profiles to discern the vertical distribution of cooling and warming. Terra and Aqua comparisons provide information about the degree to which morning and afternoon occurrences of regimes affect the symmetry of CR radiative contribution. We examine how the radiative discrepancies among multiple irradiance datasets suffering from imperfect spatiotemporal matching depend on CR, and whether they are therefore related to the complexity of cloud structure, its interpretation by different observational systems, and its subsequent representation in radiative transfer calculations.

IgSF9b forms a novel subsynaptic domain for adhesion that links to the gephyrin- and GABAA receptor–containing domain to promote inhibitory synaptic development.

Leukocyte common antigen-related receptor protein tyrosine phosphatases-comprising LAR, PTPδ, and PTPσ-are synaptic adhesion molecules that organize synapse development. Here, we identify glypican 4 (GPC-4) as a ligand for PTPσ. GPC-4 showed strong (nanomolar) affinity and heparan sulfate (HS)-dependent interaction with the Ig domains of PTPσ. PTPσ bound only to proteolytically cleaved GPC-4 and formed additional complex with leucine-rich repeat transmembrane protein 4 (LRRTM4) in rat brains. Moreover, single knockdown (KD) of PTPσ, but not LAR, in cultured neurons significantly reduced the synaptogenic activity of LRRTM4, a postsynaptic ligand of GPC-4, in heterologous synapse-formation assays. Finally, PTPσ KD dramatically decreased both the frequency and amplitude of excitatory synaptic transmission. This effect was reversed by wild-type PTPσ, but not by a HS-binding-defective PTPσ mutant. Our results collectively suggest that presynaptic PTPσ, together with GPC-4, acts in a HS-dependent manner to maintain excitatory synapse development and function.PTPσ | glypican | LRRTM4 | synaptic cell adhesion | heparan sulfate

Tapeworms of the genus Spirometra are pseudophyllidean cestodes endemic in Korea. At present, it is unclear which Spirometra species are responsible for causing human infections, and little information is available on the epidemiological profiles of Spirometra species infecting humans in Korea. Between 1979 and 2009, a total of 50 spargana from human patients and 2 adult specimens obtained from experimentally infected carnivorous animals were analyzed according to genetic and taxonomic criteria and classified as Spirometra erinaceieuropaei or Spirometra decipiens depending on the morphology. Morphologically, S. erinaceieuropaei and S. decipiens are different in that the spirally coiled uterus in S. erinaceieuropaei has 5-7 complete coils, while in S. decipiens it has only 4.5 coils. In addition, there is a 9.3% (146/1,566) sequence different between S. erinaceieuropaei and S. decipiens in the cox1 gene. Partial cox1 sequences (390 bp) from 35 Korean isolates showed 99.4% (388/390) similarity with the reference sequence of S. erinaceieuropaei from Korea (G1724; GenBank KJ599680) and an additional 15 Korean isolates revealed 99.2% (387/390) similarity with the reference sequences of S. decipiens from Korea (G1657; GenBank KJ599679). Based on morphologic and molecular databases, the estimated population ratio of S. erinaceieuropaei to S. decipiens was 35: 15. Our results indicate that both S. erinaceieuropaei and S. decipiens found in Korea infect humans, with S. erinaceieuropaei being 2 times more prevalent than S. decipiens. This study is the first to report human sparganosis caused by S. decipiens in humans in Korea.