Preparation of azide biosynthetic surrogates of myo-Inositol

As a prelude to biomolecular incorporation studies, practical routes to a series of four regioisomeric azido-deoxy derivatives of inositol that mimic the natural myo-stereochemistry are described. Starting from commercially available myo-inositol, the regioselective and stereoselective introduction of azide functionality was achieved at the C-2, C-3, C-4 and C-5 positions via azide displacement of the corresponding O-sulfonates of suitably protected scyllo-, chiro-, epi- and neo-inositols, respectively. Notably, a final one-pot acetolysis method conveniently allowed for rapid access to pentaacetate azido-deoxy inositols. Investigations on the metabolic incorporation of these myo-inositol azide surrogates in both acetate and free alcohol forms are in progress

Seawater-peridotite interactions : first insights from ODP Leg 209, MAR 15°N

Author Posting. © American Geophysical Union, 2004. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 5 (2004): Q09F26, doi:10.1029/2004GC000744.We present first results of a petrographic study of hydrothermally altered peridotites drilled during Ocean Drilling Program (ODP) Leg 209 in the 15°20′N fracture Zone area on the Mid-Atlantic Ridge (MAR). We find that serpentinization is extensive at all drill sites. Where serpentinization is incomplete, phase relations indicate two major reaction pathways. One is reaction of pyroxene to talc and tremolite, and the other is reaction of olivine to serpentine, magnetite, and brucite. We interpret these reactions in the light of recent peridotite-seawater reaction experiments and compositions of fluids venting from peridotite massifs at a range of temperatures. We suggest that the replacement of pyroxene by talc and tremolite takes place at temperatures >350°–400°C, where olivine is stable. The breakdown of olivine to serpentine, magnetite, and brucite is favored at temperatures below 250°C, where olivine reacts faster then pyroxene. High-temperature hydrothermal fluids venting at the Logatchev and Rainbow sites are consistent with rapid reaction of pyroxene and little or no reaction of olivine. Moderate-temperature fluids venting at the Lost City site are consistent with ongoing reaction of olivine to serpentine and brucite. Many completely serpentinized peridotites lack brucite and talc because once the more rapidly reacting phase is exhausted, interaction with the residual phase will change fluid pH and silica activity such that brucite or talc react to serpentine. At two sites we see strong evidence for continued fluid flow and fluid-rock interaction after serpentinization was complete. At Site 1268, serpentinites underwent massive replacement by talc under static conditions. This reaction requires either removal of Mg from or addition of Si to the system. We propose that the talc-altered rocks are Si-metasomatized and that the source of Si is likely gabbro-seawater reaction or breakdown of pyroxene deeper in the basement. The basement at Site 1268 is heavily veined, with talc and talc-oxide-sulfide veins being the most common vein types. It appears that the systems evolved from reducing (oxygen fugacity buffered by magnetite-pyrrhotite-pyrite and lower) to oxidizing (dominantly hematite). We propose that this transition is indicative of high fluid flux under retrograde conditions and that the abundance of hematite may relate to the Ca-depleted nature of the basement that prevents near-quantitative removal of seawater sulfate by anhydrite precipitation. At site 1272 we find abundant iowaite partly replacing brucite. While this is the first report of iowaite from a mid-ocean ridge setting, its presence indicates, again, fairly oxidizing conditions. Our preliminary results indicate that peridotite-seawater and serpentinite-seawater interactions can take place under a wider range of temperature and redox conditions than previously appreciated.This research used data and/or samples supplied by the Ocean Drilling Program (ODP). ODP is sponsored by the U.S. National Science Foundation (NSF) and participating countries under management of Joint Oceanographic Institutions (JOI), Inc

Carbonate veins trace seawater circulation during exhumation and uplift of mantle rock : results from ODP Leg 209

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Earth and Planetary Science Letters 311 (2011): 242–252, doi:10.1016/j.epsl.2011.09.021.Carbonate veins hosted in ultramafic basement drilled at two sites in the Mid Atlantic Ridge 15°N area record two different stages of fluid-basement interaction. A first generation of carbonate veins consists of calcite and dolomite that formed syn- to postkinematically in tremolite–chlorite schists and serpentine schists that represent gently dipping large-offset faults. These veins formed at temperatures between 90 and 170 °C (oxygen isotope thermometry) and from fluids that show intense exchange of Sr and Li with the basement (87Sr/86Sr = 0.70387 to 0.70641, δ7LiL-SVEC = + 3.3 to + 8.6‰). Carbon isotopic compositions range to high δ13CPDB values (+ 8.7‰), indicating that methanogenesis took place at depth. The Sr–Li–C isotopic composition suggests temperatures of fluid-rock interaction that are much higher (T > 350–400 °C) than the temperatures of vein mineral precipitation inferred from oxygen isotopes. A possible explanation for this discrepancy is that fluids cooled conductively during upflow within the presumed detachment fault. Aragonite veins were formed during the last 130 kyrs at low-temperatures within the uplifted serpentinized peridotites. Chemical and isotopic data suggest that the aragonites precipitated from cold seawater, which underwent overall little exchange with the basement. Oxygen isotope compositions indicate an increase in formation temperature of the veins by 8–12 °C within the uppermost ~ 80 m of the subseafloor. This increase corresponds to a high regional geothermal gradient of 100–150 °C/km, characteristic of young lithosphere undergoing rapid uplift.WB, MR, and NJ thank the Deutsche Forschungsgemeinschaft (grant no. BA1605/2) for funding. NJ acknowledges support from the DFG-Research Center/Excellence Cluster, The Ocean in the Earth Syste

Comparing cortical signatures of atrophy between late-onset and autosomal dominant Alzheimer disease

Defining a signature of cortical regions of interest preferentially affected by Alzheimer disease (AD) pathology may offer improved sensitivity to early AD compared to hippocampal volume or mesial temporal lobe alone. Since late-onset Alzheimer disease (LOAD) participants tend to have age-related comorbidities, the younger-onset age in autosomal dominant AD (ADAD) may provide a more idealized model of cortical thinning in AD. To test this, the goals of this study were to compare the degree of overlap between the ADAD and LOAD cortical thinning maps and to evaluate the ability of the ADAD cortical signature regions to predict early pathological changes in cognitively normal individuals. We defined and analyzed the LOAD cortical maps of cortical thickness in 588 participants from the Knight Alzheimer Disease Research Center (Knight ADRC) and the ADAD cortical maps in 269 participants from the Dominantly Inherited Alzheimer Network (DIAN) observational study. Both cohorts were divided into three groups: cognitively normal controls (nADRC = 381; nDIAN = 145), preclinical (nADRC = 153; nDIAN = 76), and cognitively impaired (nADRC = 54; nDIAN = 48). Both cohorts underwent clinical assessments, 3T MRI, and amyloid PET imaging with either 11C-Pittsburgh compound B or 18F-florbetapir. To generate cortical signature maps of cortical thickness, we performed a vertex-wise analysis between the cognitively normal controls and impaired groups within each cohort using six increasingly conservative statistical thresholds to determine significance. The optimal cortical map among the six statistical thresholds was determined from a receiver operating characteristic analysis testing the performance of each map in discriminating between the cognitively normal controls and preclinical groups. We then performed within-cohort and cross-cohort (e.g. ADAD maps evaluated in the Knight ADRC cohort) analyses to examine the sensitivity of the optimal cortical signature maps to the amyloid levels using only the cognitively normal individuals (cognitively normal controls and preclinical groups) in comparison to hippocampal volume. We found the optimal cortical signature maps were sensitive to early increases in amyloid for the asymptomatic individuals within their respective cohorts and were significant beyond the inclusion of hippocampus volume, but the cortical signature maps performed poorly when analyzing across cohorts. These results suggest the cortical signature maps are a useful MRI biomarker of early AD-related neurodegeneration in preclinical individuals and the pattern of decline differs between LOAD and ADAD.Fil: Dincer, Aylin. Washington University in St. Louis; Estados UnidosFil: Gordon, Brian A.. Washington University in St. Louis; Estados UnidosFil: Hari-Raj, Amrita. Ohio State University; Estados UnidosFil: Keefe, Sarah J.. Washington University in St. Louis; Estados UnidosFil: Flores, Shaney. Washington University in St. Louis; Estados UnidosFil: McKay, Nicole S.. Washington University in St. Louis; Estados UnidosFil: Paulick, Angela M.. Washington University in St. Louis; Estados UnidosFil: Shady Lewis, Kristine E.. University of Kentucky; Estados UnidosFil: Feldman, Rebecca L.. Washington University in St. Louis; Estados UnidosFil: Hornbeck, Russ C.. Washington University in St. Louis; Estados UnidosFil: Allegri, Ricardo Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Ances, Beau M.. Washington University in St. Louis; Estados UnidosFil: Berman, Sarah B.. University of Pittsburgh; Estados UnidosFil: Brickman, Adam M.. Columbia University; Estados UnidosFil: Brooks, William S.. Neuroscience Research Australia; Australia. University of New South Wales; AustraliaFil: Cash, David M.. UCL Queen Square Institute of Neurology; Reino UnidoFil: Chhatwal, Jasmeer P.. Harvard Medical School; Estados UnidosFil: Farlow, Martin R.. Indiana University; Estados UnidosFil: Fougère, Christian la. German Center for Neurodegenerative Diseases; Alemania. University Hospital of Tübingen; AlemaniaFil: Fox, Nick C.. UCL Queen Square Institute of Neurology; Reino UnidoFil: Fulham, Michael J.. Royal Prince Alfred Hospital; Australia. University of Sydney; AustraliaFil: Jack, Clifford R.. Mayo Clinic; Estados UnidosFil: Joseph-Mathurin, Nelly. Washington University in St. Louis; Estados UnidosFil: Karch, Celeste M.. Washington University in St. Louis; Estados UnidosFil: Lee, Athene. University Brown; Estados UnidosFil: Levin, Johannes. German Center for Neurodegenerative Diseases; Alemania. Ludwig Maximilians Universitat; Alemania. Munich Cluster for Systems Neurology; AlemaniaFil: Masters, Colin L.. University of Melbourne; AustraliaFil: McDade, Eric M.. Washington University in St. Louis; Estados UnidosFil: Oh, Hwamee. University Brown; Estados UnidosFil: Perrin, Richard J.. Washington University in St. Louis; Estados Unido

Recent Developments in Fluorescence Correlation Spectroscopy for Diffusion Measurements in Planar Lipid Membranes

Fluorescence correlation spectroscopy (FCS) is a single molecule technique used mainly for determination of mobility and local concentration of molecules. This review describes the specific problems of FCS in planar systems and reviews the state of the art experimental approaches such as 2-focus, Z-scan or scanning FCS, which overcome most of the artefacts and limitations of standard FCS. We focus on diffusion measurements of lipids and proteins in planar lipid membranes and review the contributions of FCS to elucidating membrane dynamics and the factors influencing it, such as membrane composition, ionic strength, presence of membrane proteins or frictional coupling with solid support

Comparing cortical signatures of atrophy between late-onset and autosomal dominant Alzheimer disease

Defining a signature of cortical regions of interest preferentially affected by Alzheimer disease (AD) pathology may offer improved sensitivity to early AD compared to hippocampal volume or mesial temporal lobe alone. Since late-onset Alzheimer disease (LOAD) participants tend to have age-related comorbidities, the younger-onset age in autosomal dominant AD (ADAD) may provide a more idealized model of cortical thinning in AD. To test this, the goals of this study were to compare the degree of overlap between the ADAD and LOAD cortical thinning maps and to evaluate the ability of the ADAD cortical signature regions to predict early pathological changes in cognitively normal individuals. We defined and analyzed the LOAD cortical maps of cortical thickness in 588 participants from the Knight Alzheimer Disease Research Center (Knight ADRC) and the ADAD cortical maps in 269 participants from the Dominantly Inherited Alzheimer Network (DIAN) observational study. Both cohorts were divided into three groups: cognitively normal controls (nADRC = 381; nDIAN = 145), preclinical (nADRC = 153; nDIAN = 76), and cognitively impaired (nADRC = 54; nDIAN = 48). Both cohorts underwent clinical assessments, 3T MRI, and amyloid PET imaging with either 11C-Pittsburgh compound B or 18F-florbetapir. To generate cortical signature maps of cortical thickness, we performed a vertex-wise analysis between the cognitively normal controls and impaired groups within each cohort using six increasingly conservative statistical thresholds to determine significance. The optimal cortical map among the six statistical thresholds was determined from a receiver operating characteristic analysis testing the performance of each map in discriminating between the cognitively normal controls and preclinical groups. We then performed within-cohort and cross-cohort (e.g. ADAD maps evaluated in the Knight ADRC cohort) analyses to examine the sensitivity of the optimal cortical signature maps to the amyloid levels using only the cognitively normal individuals (cognitively normal controls and preclinical groups) in comparison to hippocampal volume. We found the optimal cortical signature maps were sensitive to early increases in amyloid for the asymptomatic individuals within their respective cohorts and were significant beyond the inclusion of hippocampus volume, but the cortical signature maps performed poorly when analyzing across cohorts. These results suggest the cortical signature maps are a useful MRI biomarker of early AD-related neurodegeneration in preclinical individuals and the pattern of decline differs between LOAD and ADAD

No more Tears without Tiers? The Impact of Indirect Settlement on liquidity use in TARGET2

We study the impact of tiered settlement on relative intraday liquidity use (liquidity consumption) for settlement banks in TARGET2. We estimate a panel data model employing transaction-level data from 2010 to 2019 which shows that a higher share of tiered payments from client banks reduces relative liquidity consumption by settlement banks. Metrics on timing, delay, and payment priorities suggest that settlement banks can make use of more leeway in settling tiered payments from client banks compared to their own payments. Payment timing as a proxy for external delay suggests that tiered payments are used to smooth settlement banks' liquidity positions. Results on payment delay within the system show no clear dynamic over time, whereas payment priorities are consistently lower for tiered payments. We conclude that to some degree settlement banks employ tiered arrangements to manage intraday liquidity more effiiently. To a certain extent this hints to "free riding" or higher recycling of liquidity from client banks' payments. However, the results are also consistent with settlement banks' monitoring role or tiered payments potentially exhibiting different characteristics which may be attributable to contractual arrangements