The Ursinus Weekly, May 5, 1924

Library campaign shows progress • Ursinus represented at YMCA conference • Asher R. Kepler addresses students • Survey taken of conditions at Princeton • Varsity defeated while scrubs defeat • Junior varsity wins • English Club holds monthly meeting • Resume of coming events proves very interesting time ahead: May Day; Junior play; Music week • Campus notables: Former student council presidents • Mr. Thomas Clemens addresses YMCA • First YW meeting under new administration • Zwing repeated Dulcyhttps://digitalcommons.ursinus.edu/weekly/2350/thumbnail.jp

The Ursinus Weekly, June 2, 1924

Faculty to lose two members • Penn State and Ursinus divide honors over week end • Glenwood alumni hold reunion • Library campaign improves by degrees • Commencement plans announced in detail • Summer session at University of Mexico • College Republican clubs • Girls Glee Club assists at Pottstown • Basketball U\u27s awarded, managers elected • Schaff semi-annual business meeting • Pupils recital of the Ursinus school of music • Hiking Club shows marked improvementhttps://digitalcommons.ursinus.edu/weekly/2354/thumbnail.jp

BACE2 distribution in major brain cell types and identification of novel substrates

β-Site APP-cleaving enzyme 1 (BACE1) inhibition is considered one of the most promising therapeutic strategies for Alzheimer's disease, but current BACE1 inhibitors also block BACE2. As the localization and function of BACE2 in the brain remain unknown, it is difficult to predict whether relevant side effects can be caused by off-target inhibition of BACE2 and whether it is important to generate BACE1-specific inhibitors. Here, we show that BACE2 is expressed in discrete subsets of neurons and glia throughout the adult mouse brain. We uncover four new substrates processed by BACE2 in cultured glia: vascular cell adhesion molecule 1, delta and notch-like epidermal growth factor-related receptor, fibroblast growth factor receptor 1, and plexin domain containing 2. Although these substrates were not prominently cleaved by BACE2 in healthy adult mice, proinflammatory TNF induced a drastic increase in BACE2-mediated shedding of vascular cell adhesion molecule 1 in CSF. Thus, although under steady-state conditions the effect of BACE2 cross-inhibition by BACE1-directed inhibitors is rather subtle, it is important to consider that side effects might become apparent under physiopathological conditions that induce TNF expression

Characterization of transport regimes and the polar dome during Arctic spring and summer using in situ aircraft measurements

Abstract. The springtime composition of the Arctic lower troposphere is to a large extent controlled by the transport of midlatitude air masses into the Arctic. In contrast, pre- cipitation and natural sources play the most important role during summer. Within the Arctic region sloping isentropes create a barrier to horizontal transport, known as the polar dome. The polar dome varies in space and time and exhibits a strong influence on the transport of air masses from mid- latitudes, enhancing transport during winter and inhibiting transport during summer. We analyzed aircraft-based trace gas measurements in the Arctic from two NETCARE airborne field campaigns (July 2014 and April 2015) with the Alfred Wegener Insti- tute Polar 6 aircraft, covering an area from Spitsbergen to Alaska (134 to 17◦ W and 68 to 83◦ N). Using these data we characterized the transport regimes of midlatitude air masses traveling to the high Arctic based on CO and CO2 mea- surements as well as kinematic 10 d back trajectories. We found that dynamical isolation of the high Arctic lower tro- posphere leads to gradients of chemical tracers reflecting dif- ferent local chemical lifetimes, sources, and sinks. In par- ticular, gradients of CO and CO2 allowed for a trace-gas- based definition of the polar dome boundary for the two mea- surement periods, which showed pronounced seasonal differences. Rather than a sharp boundary, we derived a transi- tion zone from both campaigns. In July 2014 the polar dome boundary was at 73.5◦ N latitude and 299–303.5 K potential temperature. During April 2015 the polar dome boundary was on average located at 66–68.5◦ N and 283.5–287.5 K. Tracer–tracer scatter plots confirm different air mass prop- erties inside and outside the polar dome in both spring and summer. Further, we explored the processes controlling the recent transport history of air masses within and outside the polar dome. Air masses within the springtime polar dome mainly experienced diabatic cooling while traveling over cold sur- faces. In contrast, air masses in the summertime polar dome were diabatically heated due to insolation. During both sea- sons air masses outside the polar dome slowly descended into the Arctic lower troposphere from above through ra- diative cooling. Ascent to the middle and upper troposphere mainly took place outside the Arctic, followed by a north- ward motion. Air masses inside and outside the polar dome were also distinguished by different chemical compositions of both trace gases and aerosol particles. We found that the fraction of amine-containing particles, originating from Arc- tic marine biogenic sources, is enhanced inside the polar dome. In contrast, concentrations of refractory black carbon are highest outside the polar dome, indicating remote pollu- tion sources. Synoptic-scale weather systems frequently disturb the transport barrier formed by the polar dome and foster ex- change between air masses from midlatitudes and polar re- gions. During the second phase of the NETCARE 2014 measurements a pronounced low-pressure system south of Resolute Bay brought inflow from southern latitudes, which pushed the polar dome northward and significantly affected trace gas mixing ratios in the measurement region. Mean CO mixing ratios increased from 77.9 ± 2.5 to 84.9 ± 4.7 ppbv between these two regimes. At the same time CO2 mix- ing ratios significantly decreased from 398.16 ± 1.01 to 393.81 ± 2.25 ppmv. Our results demonstrate the utility of applying a tracer-based diagnostic to determine the polar dome boundary for interpreting observations of atmospheric composition in the context of transport history

Mouse brain proteomics establishes MDGA1 and CACHD1 as in vivo substrates of the Alzheimer protease BACE1

The protease beta-site APP cleaving enzyme 1 (BACE1) has fundamental functions in the nervous system. Its inhibition is a major therapeutic approach in Alzheimer's disease, because BACE1 cleaves the amyloid precursor protein (APP), thereby catalyzing the first step in the generation of the pathogenic amyloid beta (A beta) peptide. Yet, BACE1 cleaves numerous additional membrane proteins besides APP. Most of these substrates have been identified in vitro, but only few were further validated or characterized in vivo. To identify BACE1 substrates with in vivo relevance, we used isotope label-based quantitative proteomics of wild type and BACE1-deficient (BACE1 KO) mouse brains. This approach identified known BACE1 substrates, including Close homolog of L1 and contactin-2, which were found to be enriched in the membrane fraction of BACE1 KO brains. VWFA and cache domain-containing protein 1 (CACHD)1 and MAM domain-containing glycosylphosphatidylinositol anchor protein 1 (MDGA1), which have functions in synaptic transmission, were identified and validated as new BACE1 substrates in vivo by immunoblots using primary neurons and mouse brains. Inhibition or deletion of BACE1 from primary neurons resulted in a pronounced inhibition of substrate cleavage and a concomitant increase in full-length protein levels of CACHD1 and MDGA1. The BACE1 cleavage site in both proteins was determined to be located within the juxtamembrane domain. In summary, this study identifies and validates CACHD1 and MDGA1 as novel in vivo substrates for BACE1, suggesting that cleavage of both proteins may contribute to the numerous functions of BACE1 in the nervous system

Vertical profiles of light absorption and scattering associated with black carbon particle fractions in the springtime Arctic above 79◦ N

Despite the potential importance of black carbon (BC) for radiative forcing of the Arctic atmosphere, ver- tically resolved measurements of the particle light scatter- ing coefficient (σsp ) and light absorption coefficient (σap ) in the springtime Arctic atmosphere are infrequent, espe- cially measurements at latitudes at or above 80◦ N. Here, re- lationships among vertically distributed aerosol optical prop- erties (σap, σsp and single scattering albedo or SSA), par- ticle microphysics and particle chemistry are examined for a region of the Canadian archipelago between 79.9 and 83.4◦ N from near the surface to 500 hPa. Airborne data collected during April 2015 are combined with ground- based observations from the observatory at Alert, Nunavut and simulations from the Goddard Earth Observing Sys- tem (GEOS) model, GEOS-Chem, coupled with the TwO- Moment Aerosol Sectional (TOMAS) model (collectively GEOS-Chem–TOMAS; Kodros et al., 2018) to further our knowledge of the effects of BC on light absorption in the Arctic troposphere. The results are constrained for σsp less than 15 Mm−1, which represent 98 % of the observed σsp, be- cause the single scattering albedo (SSA) has a tendency to be lower at lower σsp, resulting in a larger relative contribution to Arctic warming. At 18.4 m2 g−1, the average BC mass ab- sorption coefficient (MAC) from the combined airborne and Alert observations is substantially higher than the two aver- aged modelled MAC values (13.6 and 9.1 m2 g−1) for two different internal mixing assumptions, the latter of which is based on previous observations. The higher observed MAC value may be explained by an underestimation of BC, the presence of small amounts of dust and/or possible differences in BC microphysics and morphologies between the obser- vations and model. In comparing the observations and simulations, we present σap and SSA, as measured, and σap/2 and the corresponding SSA to encompass the lower modelled MAC that is more consistent with accepted MAC values. Me- dian values of the measured σap, rBC and the organic com- ponent of particles all increase by a factor of 1.8 ± 0.1, going from near-surface to 750 hPa, and values higher than the sur- face persist to 600 hPa. Modelled BC, organics and σap agree with the near-surface measurements but do not reproduce the higher values observed between 900 and 600 hPa. The dif- ferences between modelled and observed optical properties follow the same trend as the differences between the mod- elled and observed concentrations of the carbonaceous com- ponents (black and organic). Model-observation discrepan- cies may be mostly due to the modelled ejection of biomass burning particles only into the boundary layer at the sources. For the assumption of the observed MAC value, the SSA range between 0.88 and 0.94, which is significantly lower than other recent estimates for the Arctic, in part reflecting the constraint of σsp < 15 Mm−1. The large uncertainties in measuring optical properties and BC, and the large differ- ences between measured and modelled values here and in the literature, argue for improved measurements of BC and light absorption by BC and more vertical profiles of aerosol chemistry, microphysics and other optical properties in the Arctic

Aircraft-based measurements of High Arctic springtime aerosol show evidence for vertically varying sources, transport and composition

The sources, chemical transformations and re- moval mechanisms of aerosol transported to the Arctic are key factors that control Arctic aerosol–climate interactions. Our understanding of sources and processes is limited by a lack of vertically resolved observations in remote Arctic re- gions. We present vertically resolved observations of trace gases and aerosol composition in High Arctic springtime, made largely north of 80◦ N, during the NETCARE cam- paign. Trace gas gradients observed on these flights defined the polar dome as north of 66–68◦ 30′ N and below poten- tial temperatures of 283.5–287.5 K. In the polar dome, we observe evidence for vertically varying source regions and chemical processing. These vertical changes in sources and chemistry lead to systematic variation in aerosol composition as a function of potential temperature. We show evidence for sources of aerosol with higher organic aerosol (OA), ammo- nium and refractory black carbon (rBC) content in the upper polar dome. Based on FLEXPART-ECMWF calculations, air masses sampled at all levels inside the polar dome (i.e., po- tential temperature 10 days) in the Arc- tic, while air masses in the upper polar dome had entered the Arctic more recently. Variations in aerosol composition were closely related to transport history. In the lower polar dome, the measured sub-micron aerosol mass was dominated by sulfate (mean 74 %), with lower contributions from rBC (1 %), ammonium (4 %) and OA (20 %). At higher altitudes and higher potential temperatures, OA, ammonium and rBC contributed 42 %, 8 % and 2 % of aerosol mass, respectively. A qualitative indication for the presence of sea salt showed that sodium chloride contributed to sub-micron aerosol in the lower polar dome, but was not detectable in the upper po- lar dome. Our observations highlight the differences in Arc- tic aerosol chemistry observed at surface-based sites and the aerosol transported throughout the depth of the Arctic tropo- sphere in spring

High Arctic aircraft measurements characterising black carbon vertical variability in spring and summer

The vertical distribution of black carbon (BC) par- ticles in the Arctic atmosphere is one of the key parameters controlling their radiative forcing and thus role in Arctic cli- mate change. This work investigates the presence and prop- erties of these light-absorbing aerosols over the High Cana- dian Arctic ( > 70 degree N). Airborne campaigns were performed as part of the NETCARE project (Network on Climate and Aerosols: Addressing Key Uncertainties in Remote Canadian Environments) and provided insights into the variability of the vertical distributions of BC particles in summer 2014 and spring 2015. The observation periods covered evolutions of cyclonic disturbances at the polar front, which favoured the transport of air pollution into the High Canadian Arctic, as otherwise this boundary between the air masses largely im- pedes entrainment of pollution from lower latitudes. A total of 48 vertical profiles of refractory BC (rBC) mass concen- tration and particle size, extending from 0.1 to 5.5 km altitude were obtained with a Single-Particle Soot Photometer (SP2). Generally, the rBC mass concentration decreased from spring to summer by a factor of 10. Such depletion was as- sociated with a decrease in the mean rBC particle diameter, from approximately 200 to 130 nm at low altitude. Due to the very low number fraction, rBC particles did not substantially contribute to the total aerosol population in summer. The analysis of profiles with potential temperature as ver- tical coordinate revealed characteristic variability patterns within specific levels of the cold and stably stratified, dome- like, atmosphere over the polar region. The associated his- tory of transport trajectories into each of these levels showed that the variability was induced by changing rates and effi- ciencies of rBC import. Generally, the source areas affecting the polar dome extended southward with increasing potential temperature (i.e. altitude) level in the dome. While the lower dome was mostly only influenced by low-level transport from sources within the cold central and marginal Arctic, for the mid-dome and upper dome during spring it was found that a cold air outbreak over eastern Europe caused intensified northward transport of air from a corridor over western Rus- sia to central Asia. This sector was affected by emissions from gas flaring, industrial activity and wildfires. The devel- opment of transport caused rBC concentrations in the second lowest level to gradually increase from 32 to 49 ng

Size-resolved mixing state of black carbon in the Canadian high Arctic and implications for simulated direct radiative effect

Transport of anthropogenic aerosol into the Arc- tic in the spring months has the potential to affect regional climate; however, modeling estimates of the aerosol direct radiative effect (DRE) are sensitive to uncertainties in the mixing state of black carbon (BC). A common approach in previous modeling studies is to assume an entirely exter- nal mixture (all primarily scattering species are in separate particles from BC) or internal mixture (all primarily scat- tering species are mixed in the same particles as BC). To provide constraints on the size-resolved mixing state of BC, we use airborne single-particle soot photometer (SP2) and ultrahigh-sensitivity aerosol spectrometer (UHSAS) mea- surements from the Alfred Wegener Institute (AWI) Polar 6 flights from the NETCARE/PAMARCMIP2015 campaign to estimate coating thickness as a function of refractory BC (rBC) core diameter and the fraction of particles contain- ing rBC in the springtime Canadian high Arctic. For rBC core diameters in the range of 140 to 220 nm, we find av- erage coating thicknesses of approximately 45 to 40 nm, re- spectively, resulting in ratios of total particle diameter to rBC core diameters ranging from 1.6 to 1.4. For total par- ticle diameters ranging from 175 to 730 nm, rBC-containing particle number fractions range from 16% to 3%, respec- tively. We combine the observed mixing-state constraints with simulated size-resolved aerosol mass and number dis- tributions from GEOS-Chem–TOMAS to estimate the DRE with observed bounds on mixing state as opposed to assuming an entirely external or internal mixture. We find that the pan-Arctic average springtime DRE ranges fro

Systematic substrate identification indicates a central role for the metalloprotease ADAM10 in axon targeting and synapse function

Metzincin metalloproteases have major roles in intercellular communication by modulating the function of membrane proteins. One of the proteases is the a-disintegrin-and-metalloprotease 10 (ADAM10) which acts as alpha-secretase of the Alzheimer\u27s disease amyloid precursor protein. ADAM10 is also required for neuronal network functions in murine brain, but neuronal ADAM10 substrates are only partly known. With a proteomic analysis of Adam10-deficient neurons we identified 91, mostly novel ADAM10 substrate candidates, making ADAM10 a major protease for membrane proteins in the nervous system. Several novel substrates, including the neuronal cell adhesion protein NrCAM, are involved in brain development. Indeed, we detected mistargeted axons in the olfactory bulb of conditional ADAM10-/- mice, which correlate with reduced cleavage of NrCAM, NCAM and other ADAM10 substrates. In summary, the novel ADAM10 substrates provide a molecular basis for neuronal network dysfunctions in conditional ADAM10-/- mice and demonstrate a fundamental function of ADAM10 in the brain