Monoclonal Antibody Identification of Subpopulations of Cerebral Cortical Neurons Affected in Alzheimer disease

Neuronal degeneration is one of the hallmarks of Alzheimer disease (AD). Given the paucity of molecular markers available for the identification of neuronal subtypes, the specificity of neuronal loss within the cerebral cortex has been difficult to evaluate. With a panel of four monoclonal antibodies (mAbs) applied to central nervous system tissues from AD patients, we have immunocytochemically identified a population of vulnerable cortical neurons; a subpopulation of pyramidal neurons is recognized by mAbs 3F12 and 44.1 in the hippocampus and neocortex, and clusters of multipolar neurons in the entorhinal cortex reactive with mAb 44.1 show selective degeneration. Closely adjacent stellate-like neurons in these regions, identified by mAb 6A2, show striking preservation in AD. The neurons recognized by mAbs 3F12 and 44.1, to the best of our knowledge, do not comprise a single known neurotransmitter system. mAb 3A4 identifies a phosphorylated antigen that is undetectable in normal brain but accumulates early in the course of AD in somas of vulnerable neurons. Antigen 3A4 is distinct from material reactive with thioflavin S or antibody generated against paired helical filaments. Initially, antigen 3A4 is localized to neurons in the entorhinal cortex and subiculum, later in the association neocortex, and, ultimately in cases of long duration, in primary sensory cortical regions. mAb 3F12 recognizes multiple bands on immunoblots of homogenates of normal and Ad cortical tissues, whereas mAb 3A4 does not bind to immunoblots containing neurofilament proteins or brain homogenates from AD patients. Ultrastructurally, antigen 3A4 is localized to paired-helical filaments. Using these mAbs, further molecular characterization of the affected cortical neurons is now possible

A Second Method to Photometrically Align Multi-Site Microlensing Light Curves: Source Color in Planetary Event MOA-2007-BLG-192

At present, microlensing light curves from different telescopes and filters are photometrically aligned by fitting them to a common model. We present a second method based on photometry of common field stars. If two spectral responses are similar (or the color of the source is known) then this technique can resolve important ambiguities that frequently arise when predicting the future course of the event, and that occasionally persist even when the event is over. Or if the spectral responses are different, it can be used to derive the color of the source when that is unknown. We present the essential elements of this technique and apply it to the case of MOA-2007-BLG-192, an important planetary event for which the system may be a terrestrial planet orbiting a brown dwarf or very low mass star. The refined estimate of the source color that we derive here, V-I=2.36 +- 0.03, will aid in making the estimate of the lens mass more precise.Comment: 16 pages including 3 figures. Submitted to Ap

Conservation of threatened relict trees through living ex situ collections: lessons from the global survey of the genus Zelkova (Ulmaceae)

Maintaining living ex situ collections is one of the key conservation methods in botanic gardens worldwide. Despite of the existence of many other conservation approaches used nowadays, it offers for many endangered plants an important insurance policy for the future, especially for rare and threatened relict trees. The aim of this research was to investigate the global extent of living ex situ collections, to assess and discuss their viability and inform the development of conservation approaches that respond to latest global conservation challenges. We used as a model taxon the tree genus Zelkova (Ulmaceae). The genus includes six prominent Tertiary relict trees which survived the last glaciation in disjunct and isolated refugial regions. Our comprehensive worldwide survey shows that the majority of botanic institutions with Zelkova collections are in countries with a strong horticultural tradition and not in locations of their origin. More importantly, the acutely threatened Zelkova species are not the most represented in collections, and thus safeguarded through ex situ conservation. Less than 20% of the ex situ collections surveyed contain plant material of known wild provenance while the majority (90%) of collections are generally very small (1-10 trees). Botanic gardens and arboreta particularly in regions where iconic relict trees naturally occur should play a vital role in the conservation of these species. The coordination of conservation efforts between gardens has to be enhanced to prioritise action for the most threatened relict trees. Large scale genetic studies should be undertaken, ideally at genus level, in order to verify or clarify the provenance of ex situ collections of relict trees in cultivation. For the most threatened relict tree genera, well-coordinated specialist groups should be create

General Relativistic Magnetohydrodynamic Simulations of the Hard State as a Magnetically-Dominated Accretion Flow

(Abridged) We present one of the first physically-motivated two-dimensional general relativistic magnetohydrodynamic (GRMHD) numerical simulations of a radiatively-cooled black-hole accretion disk. The fiducial simulation combines a total-energy-conserving formulation with a radiative cooling function, which includes bremsstrahlung, synchrotron, and Compton effects. By comparison with other simulations we show that in optically thin advection-dominated accretion flows, radiative cooling can significantly affect the structure, without necessarily leading to an optically thick, geometrically thin accretion disk. We further compare the results of our radiatively-cooled simulation to the predictions of a previously developed analytic model for such flows. For the very low stress parameter and accretion rate found in our simulated disk, we closely match a state called the "transition" solution between an outer advection-dominated accretion flow and what would be a magnetically-dominated accretion flow (MDAF) in the interior. The qualitative and quantitative agreement between the numerical and analytic models is quite good, with only a few well-understood exceptions. According to the analytic model then, at significantly higher stress or accretion, we would expect a full MDAF to form. The collection of simulations in this work also provide important data for interpreting other numerical results in the literature, as they span the most common treatments of thermodynamics, including simulations evolving: 1) the internal energy only; 2) the internal energy plus an explicit cooling function; 3) the total energy without cooling; and 4) total energy including cooling. We find that the total energy formulation is a necessary prerequisite for proper treatment of radiative cooling in MRI accretion flows.Comment: 13 pages, 7 figures, submitted to Ap

The Tertiary relict tree Zelkova abelicea (Ulmaceae): distribution, population structure and conservation status on Crete

Relict species provide a unique opportunity to understand past and recent biogeographical and evolutionary processes. Zelkova abelicea (Ulmaceae), which is endemic to the island of Crete (Greece), is one of the most prominent Tertiary relict trees of the Mediterranean region. We collected distribution, threat and population structure data by reviewing literature and herbaria and through field surveys at 14 study plots throughout the range of the species. The present distribution of Z. abelicea is extremely fragmented. Although the total estimated number of individuals is relatively high, the populations are dominated by dwarf, severely browsed, non-flowering individuals. The population structure is asymmetric. At most, 5% of a plot's trees are large and fruit-bearing. The asymmetric structure is particularly pronounced in isolated and small populations. Based on its limited geographical range, the fragmented spatial pattern, and data on distribution and population structure, our study confirms that Z. abelicea is a threatened species (IUCN category Endangered). Our research aim is to promote the development of new approaches for the improvement of conservation strategies for Tertiary relict trees characterized by major local disjunction

The Grizzly, December 7, 1993

UC Area Code to Change • Greetings, from Skye • Progress Made on Trade Agreement • UC Mourns Loss of Senior • Silenced by Propaganda • Exam Schedule • The Steps of Bomberger • Four One-Act Plays to be Performedhttps://digitalcommons.ursinus.edu/grizzlynews/1327/thumbnail.jp

The Grizzly, May 4, 1993

Yeltsin Receives Vote of Confidence • Snakes, Crocs, and Turtles: Reptile World Comes to Ursinus • $10,000 Scholarship Awarded to Ursinus Sophomore • Bernie Bernie Headflap Plays Wismer Lower Lounge • Exam Schedule • U.S.G.A. Minutes • Student Art Awards Given • Sports Shortshttps://digitalcommons.ursinus.edu/grizzlynews/1317/thumbnail.jp

The Experimental Regional Ensemble Forecast System (ExREF): Its Use in NWS Forecast Operations and Preliminary Verification

The Experimental Regional Ensemble Forecast (ExREF) system is a tool for the development and testing of new Numerical Weather Prediction (NWP) methodologies. ExREF is run in nearrealtime by the Global Systems Division (GSD) of the NOAA Earth System Research Laboratory (ESRL) and its products are made available through a website, an ftp site, and via the Unidata Local Data Manager (LDM). The ExREF domain covers most of North America and has 9km horizontal grid spacing. The ensemble has eight members, all employing WRFARW. The ensemble uses a variety of initial conditions from LAPS and the Global Forecasting System (GFS) and multiple boundary conditions from the GFS ensemble. Additionally, a diversity of physical parameterizations is used to increase ensemble spread and to account for the uncertainty in forecasting extreme precipitation events. ExREF has been a component of the Hydrometeorology Testbed (HMT) NWP suite in the 20122013 and 20132014 winters. A smaller domain covering just the West Coast was created to minimize bandwidth consumption for the NWS. This smaller domain has and is being distributed to the National Weather Service (NWS) Weather Forecast Office and California Nevada River Forecast Center in Sacramento, California, where it is ingested into the Advanced Weather Interactive Processing System (AWIPS I and II) to provide guidance on the forecasting of extreme precipitation events. This paper will review the cooperative effort employed by NOAA ESRL, NASA SPoRT (Shortterm Prediction Research and Transition Center), and the NWS to facilitate the ingest and display of ExREF data utilizing the AWIPS I and II D2D and GFE (Graphical Software Editor) software. Within GFE is a very useful verification software package called BoiVer that allows the NWS to utilize the River Forecast Center's 4 km gridded QPE to compare with all operational NWP models 6hr QPF along with the ExREF mean 6hr QPF so the forecasters can build confidence in the use of the ExREF in preparing their rainfall forecasts. Preliminary results will be presented

Postnatal Pancreas of Mice Contains Tripotent Progenitors Capable of Giving Rise to Duct, Acinar, and Endocrine Cells In Vitro

Postnatal pancreas is a potential source for progenitor cells to generate endocrine β-cells for treating type 1 diabetes. However, it remains unclear whether young (1-week-old) pancreas harbors multipotent progenitors capable of differentiating into duct, acinar, and endocrine cells. Laminin is an extracellular matrix (ECM) protein important for β-cells' survival and function. We established an artificial extracellular matrix (aECM) protein that contains the functional IKVAV (Ile-Lys-Val-Ala-Val) sequence derived from laminin (designated aECM-lam). Whether IKVAV is necessary for endocrine differentiation in vitro is unknown. To answer these questions, we cultured single cells from 1-week-old pancreas in semi-solid media supplemented with aECM-lam, aECM-scr (which contains a scrambled sequence instead of IKVAV), or Matrigel. We found that colonies were generated in all materials. Individual colonies were examined by microfluidic reverse transcription-polymerase chain reaction, immunostaining, and electron microscopy analyses. The majority of the colonies expressed markers for endocrine, acinar, and ductal lineages, demonstrating tri-lineage potential of individual colony-forming progenitors. Colonies grown in aECM-lam expressed higher levels of endocrine markers Insulin1, Insulin2, and Glucagon compared with those grown in aECM-scr and Matrigel, indicating that the IKVAV sequence enhances endocrine differentiation. In contrast, Matrigel was inhibitory for endocrine gene expression. Colonies grown in aECM-lam displayed the hallmarks of functional β-cells: mature insulin granules and glucose-stimulated insulin secretion. Colony-forming progenitors were enriched in the CD133^(high) fraction and among 230 micro-manipulated single CD133^(high) cells, four gave rise to colonies that expressed tri-lineage markers. We conclude that young postnatal pancreas contains multipotent progenitor cells and that aECM-lam promotes differentiation of β-like cells in vitro

Impact of Th1 CD4 Follicular Helper T Cell Skewing on Antibody Responses to an HIV-1 Vaccine in Rhesus Macaques.

Generating durable humoral immunity through vaccination depends upon effective interactions of follicular helper T (Tfh) cells with germinal center (GC) B cells. Th1 polarization of Tfh cells is an important process shaping the success of Tfh-GC B cell interactions by influencing costimulatory and cytokine-dependent Tfh help to B cells. However, the question remains as to whether adjuvant-dependent modulation of Tfh cells enhances HIV-1 vaccine-induced antienvelope (anti-Env) antibody responses. We investigated whether an HIV-1 vaccine platform designed to increase the number of Th1-polarized Tfh cells enhances the magnitude and quality of anti-Env antibodies. Utilizing a novel interferon-induced protein 10 (IP-10)-adjuvanted HIV-1 DNA prime followed by a monophosphoryl lipid A and QS-21 (MPLA+QS-21)-adjuvanted Env protein boost (DIP-10 PALFQ) in macaques, we observed higher anti-Env serum IgG titers with greater cross-clade reactivity, specificity for V1V2, and effector functions than in macaques primed with DNA lacking IP-10 and boosted with MPLA-plus-alum-adjuvanted Env protein (DPALFA) The DIP-10 PALFQ vaccine regimen elicited higher anti-Env IgG1 and lower IgG4 antibody levels in serum, showing for the first time that adjuvants can dramatically impact the IgG subclass profile in macaques. The DIP-10 PALFQ regimen also increased vaginal and rectal IgA antibodies to a greater extent. Within lymph nodes, we observed augmented GC B cell responses and the promotion of Th1 gene expression profiles in GC Tfh cells. The frequency of GC Tfh cells correlated with both the magnitude and avidity of anti-Env serum IgG. Together, these data suggest that adjuvant-induced stimulation of Th1-Tfh cells is an effective strategy for enhancing the magnitude and quality of anti-Env antibody responses.IMPORTANCE The results of the RV144 trial demonstrated that vaccination could prevent HIV transmission in humans and that longevity of anti-Env antibodies may be key to this protection. Efforts to improve upon the prime-boost vaccine regimen used in RV144 have indicated that booster immunizations can increase serum anti-Env antibody titers but only transiently. Poor antibody durability hampers efforts to develop an effective HIV-1 vaccine. This study was designed to identify the specific elements involved in the immunological mechanism necessary to produce robust HIV-1-specific antibodies in rhesus macaques. By clearly defining immune-mediated pathways that improve the magnitude and functionality of the anti-HIV-1 antibody response, we will have the foundation necessary for the rational development of an HIV-1 vaccine