ALBERT

Description: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder in which patients carry premutation alleles of 55–200 CGG repeats in the FMR1 gene. To date, whether alterations in epigenetic regulation modulate FXTAS has gone unexplored. 5-Hydroxymethylcytosine (5hmC) converted from 5-methylcytosine (5mC) by the ten-eleven translocation (TET) family of proteins has been found recently to play key roles in neuronal functions. Here, we undertook genome-wide profiling of cerebellar 5hmC in a FXTAS mouse model (rCGG mice) and found that rCGG mice at 16 weeks showed overall reduced 5hmC levels genome-wide compared with age-matched wild-type littermates. However, we also observed gain-of-5hmC regions in repetitive elements, as well as in cerebellum-specific enhancers, but not in general enhancers. Genomic annotation and motif prediction of wild-type- and rCGG-specific differential 5-hydroxymethylated regions (DhMRs) revealed their high correlation with genes and transcription factors that are important in neuronal developmental and functional pathways. DhMR-associated genes partially overlapped with genes that were differentially associated with ribosomes in CGG mice identified by bacTRAP ribosomal profiling. Taken together, our data strongly indicate a functional role for 5hmC-mediated epigenetic modulation in the etiology of FXTAS, possibly through the regulation of transcription.

Description: Determining the molecular mechanism(s) leading to Purkinje neuron loss in the neurodegenerative disorder fragile X-associated tremor/ataxia syndrome (FXTAS) is limited by the complex morphology of this cell type. Purkinje neurons are notoriously difficult to isolate and maintain in culture presenting considerable difficultly to identify molecular changes in response to expanded CGG repeat (rCGG)-containing mRNA that induces neurotoxicity in FXTAS. Several studies have uncovered a number of RNA-binding proteins involved in translation that aberrantly interact with the CGG-containing RNA; however, whether these interactions alter the translational profile of cells has not been investigated. Here we employ bacTRAP translational profiling to demonstrate that Purkinje neurons ectopically expressing 90 CGG repeats exhibit a dramatic change in their translational profile even prior to the onset of rCGG-induced phenotypes. This approach identified ~500 transcripts that are differentially associated with ribosomes in r(CGG) 90 -expressing mice. Functional annotation cluster analysis revealed broad ontologies enriched in the r(CGG) 90 list, including RNA binding and response to stress. Intriguingly, a transcript for the Tardbp gene, implicated in a number of other neurodegenerative disorders, exhibits altered association with ribosomes in the presence of r(CGG) 90 repeats. We therefore tested and showed that reduced association of Tardbp mRNA with the ribosomes results in a loss of TDP-43 protein expression in r(CGG) 90 -expressing Purkinje neurons. Furthermore, we showed that TDP-43 could modulate the rCGG repeat-mediated toxicity in a Drosophila model that we developed previously. These findings together suggest that translational dysregulation may be an underlying mechanism of rCGG-induced neurotoxicity in FXTAS.

Description: Nitrous oxide (N2O) is the largest known remaining anthropogenic threat to the stratospheric ozone layer. However, it is currently only regulated under the 1997 Kyoto Protocol because of its simultaneous ability to warm the climate. The threat N2O poses to the stratospheric ozone layer, coupled with the uncertain future of...

Description: Understanding the sensitivity of Earth's climate to an imposed external forcing is one of the great challenges in science and a critical component of efforts to avoid dangerous anthropogenic interference with the climate system. Climate sensitivity (or equilibrium global surface warming) to a doubling of atmospheric CO2 has long been estimated to be about 3 °C, considering only fast climate feedbacks associated with increases in water vapor, decreases in sea ice, and changes in clouds. However, evidence from Earth's history suggests that slower surface albedo feedbacks due to vegetation change and melting of Greenland and Antarctica can come into play on the timescales of interest to humans, which could increase the sensitivity to significantly higher values, as much as 6 °C. Even higher sensitivity may result as present-day land and ocean carbon sinks begin to lose their ability to sequester anthropogenic CO2 in the coming decades. The evolving view of climate sensitivity in the Anthropocene is therefore one in which a wider array of Earth system feedbacks are recognized as important. Since these feedbacks are overwhelmingly positive, the sensitivity is likely to be higher than has traditionally been assumed.

Description: Dichotomous aerosols (nominal super- and sub-μm-diameter size fractions) in sectored on-shore flow were sampled daily from July 2006 through June 2009, at the Tudor Hill Atmospheric Observatory (THAO) on the western coast of Bermuda (32.27° N, 64.87° W) and analyzed for major chemical and physical properties. Flexpart retroplumes were calculated for each sampling period and aerosol properties were stratified accordingly based on transport from different regions. Transport from the northeastern United States (NEUS) was associated with significantly higher (factors of 2 to 3 based on median values) concentrations of bulk particulate non-sea-salt (nss) SO42−, NO3−, and NH4+ and associated scattering and absorption at 530 nm, relative to transport from Africa (AFR) and the Oceanic background. These differences were driven primarily by higher values associated with the sub-μm size fraction under NEUS flow. We estimate that 75 (± 3)% of the NEUS nss SO42− was anthropogenic in origin, while only 25 (± 9)% of the AFR nss SO42− was anthropogenic. Integrating over all transport patterns, we estimate the contribution of anthropogenic sulfate has dropped 14.6% from the early 1990's. Bulk scattering was highly correlated with bulk nss SO42− in all flow regimes but the corresponding regression slopes varied significantly reflecting differential contributions to total scattering by associated aerosol components. Absorption by super-μm aerosol in transport from the NEUS versus AFR was similar although the super-μm aerosol size fraction accounted for a relatively greater contribution to total absorption in AFR flow. Significantly greater absorption angstrom exponents (AAEs) for AFR flow reflects the wavelength dependence of absorption by mineral aerosols; lower AAEs for NEUS flow is consistent with the dominance of absorption by combustion-derived aerosols. Higher AOD associated with transport from both the NEUS and AFR relative to Oceanic background flow results in a top of atmosphere direct radiative forcing on the order of −1.6 to −2.5 W m−2, respectively, showing these aerosols drive cooling. The dominance of transport from the NEUS on an annual basis coupled with the corresponding decreases in anthropogenic nss SO42− aerosols since the early 1990's implies that emission reductions in the US account for a decline in atmospheric cooling over the western North Atlantic Ocean during this period.

Description: Since the 1980s, emissions of SO2 and NOx (NO + NO2) from anthropogenic sources in the United States (US) and Europe have decreased significantly suggesting that the export of oxidized S and N compounds from surrounding continents to the atmosphere overlying North Atlantic Ocean (NAO) has also decreased. The chemical compositions of aerosols and precipitation sampled daily on Bermuda (32.27° N, 64.87° W) from 1989 to 1997 and from 2006 to 2009 were evaluated to quantify the magnitudes, significance, and implications of associated tends in atmospheric composition. The chemical data were stratified based on FLEXPART retroplumes into four discrete transport regimes: westerly flow from the eastern North America (NEUS/SEUS); easterly trade-wind flow from northern Africa and the subtropical NAO (Africa); long, open-ocean, anticyclonic flow around the Bermuda High (Oceanic); and transitional flow from the relatively clean open ocean to the polluted northeastern US (North). Based on all data, annual average concentrations of non-sea-salt (nss) SO42- associated with aerosols and annual VWA concentrations in precipitation decreased significantly (by 22 and 49%, respectively) whereas annual VWA concentrations of NH4+ in precipitation increased significantly (by 70%). Corresponding trends in aerosol and precipitation NO3- and of aerosol NH4+ were insignificant. Nss SO42- in precipitation under NEUS/SEUS and Oceanic flow decreased significantly (61% each) whereas corresponding trends in particulate nss SO42- under both flow regimes were insignificant. Trends for precipitation were driven in part by decreasing emissions of SO2 over upwind continents and associated decreases in anthropogenic contributions to nss SO42- concentrations. Under NEUS/SEUS and Oceanic flow, the ratio of anthropogenic to biogenic contributions to to nss SO42- in the column scavenged by precipitation were relatively greater than those in near surface aerosol, which implies that, for these flow regimes, precipitation is a better indicator of overall anthropogenic impacts on the lower troposphere. Particulate nss SO42- under African flow also decreased significantly (34%) whereas the corresponding decrease in nss SO42- associated with precipitation was marginally insignificant. We infer that these trends were driven in part by reductions in the emissions and transport of oxidized S compounds from Europe. The lack of significant trends in NO3- associated with aerosols and precipitation under NEUS/SEUS flow is notable in light of the large decrease (39%) in NOx emissions in the US over the period of record. Rapid chemical processing of oxidized N in marine air contributed to this lack of correspondence. Decreasing ratios of nss SO42- to NH4+ and the significant decreasing trend in precipitation acidity (37%) indicate that the total amount of acidity in the multiphase gas-aerosol system in the western NAO troposphere decreased over the period of record. Decreasing aerosol acidities would have shifted the phase partitioning of total NH3 (NH3 + particulate NH4+) towards the gas phase thereby decreasing the atmospheric lifetime of total NH3 against wet plus dry deposition. The trend of increasing NH4+ in precipitation at Bermuda over the period of record suggests that NH3 emissions from surrounding continents also increased. Decreasing particulate nss SO42- in near-surface air under NEUS/SEUS flow over the period of record suggests a lower limit for net warming in the range of 0.1–0.3 W m-2 resulting from the decreased shortwave scattering and absorption by nss SO42- and associated aerosol constituents.

Description: Since the 1980s, emissions of SO2 and NOx (NO + NO2) from anthropogenic sources in the United States (US), Canada, and Europe have decreased significantly suggesting that the export of oxidized S and N compounds from surrounding continents to the atmosphere overlying the North Atlantic Ocean (NAO) has also decreased. The chemical compositions of aerosols and precipitation sampled daily on Bermuda (32.27° N, 64.87° W) from 1989 to 1997 and from 2006 to 2009 were evaluated to quantify the magnitudes, significance, and implications of associated tends in atmospheric composition. The chemical data were stratified based on FLEXPART (FLEXible PARTicle dispersion model) retroplumes into four discrete transport regimes: westerly flow from eastern North America (NEUS/SEUS); easterly trade-wind flow from northern Africa and the subtropical NAO (Africa); long, open-ocean, anticyclonic flow around the Bermuda High (Oceanic); and transitional flow from the relatively clean open ocean to the polluted eastern North America (North). Based on all data, annual average concentrations of non-sea-salt (nss) SO42– associated with aerosols and annual volume-weighted-average (VWA) concentrations in precipitation decreased significantly (by 22% and 49%, respectively) whereas annual VWA concentrations of NH4+ in precipitation increased significantly (by 70%). Corresponding trends in aerosol and precipitation NO3– and of aerosol NH4+ were insignificant. Nss SO42– in precipitation under NEUS/SEUS and Oceanic flow decreased significantly (61% each) whereas corresponding trends in particulate nss SO42– under both flow regimes were insignificant. Trends in precipitation composition were driven in part by decreasing emissions of SO2 over upwind continents and associated decreases in anthropogenic contributions to nss SO42– concentrations. Under NEUS/SEUS and Oceanic flow, the ratio of anthropogenic to biogenic contributions to nss SO42– in the column scavenged by precipitation were relatively greater than those in near surface aerosol, which implies that, for these flow regimes, precipitation is a better indicator of overall anthropogenic impacts on the lower troposphere. Particulate nss SO42– under African flow also decreased significantly (34%) whereas the corresponding decrease in nss SO42– associated with precipitation was insignificant. We infer that these trends were driven in part by reductions in the emissions and transport of oxidized S compounds from Europe. The lack of significant trends in NO3– associated with aerosols and precipitation under NEUS/SEUS flow is notable in light of the large decrease (37%) in NOx emissions in the US and Canada over the period of record. Rapid chemical processing of oxidized N in marine air contributed to this lack of correspondence. Decreasing ratios of nss SO42– to NH4+ and the significant decreasing trend in precipitation acidity (37%) indicate that the total amount of acidity in the multiphase gas–aerosol system in the western NAO troposphere decreased over the period of record. Decreasing aerosol acidities would have shifted the phase partitioning of total NH3 (NH3 + particulate NH4+ towards the gas phase thereby decreasing the atmospheric lifetime of total NH3 against wet plus dry deposition. The trend of increasing NH4+ in precipitation at Bermuda over the period of record suggests that NH3 emissions from surrounding continents also increased. Decreasing particulate nss SO42– in near-surface air under NEUS/SEUS flow over the period of record implies that the corresponding shortwave scattering and absorption by nss S and associated aerosols constituents also decreased. These changes in radiative transfer suggest a corresponding lower limit for net warming over the period in the range of 0.1–0.3 W m–2.

Description: Dichotomous aerosols (nominal super- and sub-μm-diameter size fractions) in sectored on-shore flow were sampled daily from July 2006 through June 2009, at the Tudor Hill Atmospheric Observatory (THAO) on the western coast of Bermuda (32.27° N, 64.87° W) and analyzed for major chemical and physical properties. FLEXPART retroplumes were calculated for each sampling period and aerosol properties were stratified accordingly based on transport from different regions. Transport from the northeastern United States (NEUS) was associated with significantly higher (factors of 2 to 3 based on median values) concentrations of bulk particulate non-sea-salt (nss) SO42-, NO3-, and NH4+ and associated scattering and absorption at 530 nm, relative to transport from Africa (AFR) and the oceanic background. These differences were driven primarily by higher values associated with the sub-μm size fraction under NEUS flow. We estimate that 75(±3)% of the NEUS nss SO42- was anthropogenic in origin, while only 25(±9)% of the AFR nss SO42- was anthropogenic. Integrating over all transport patterns, the contribution of anthropogenic sulfate has dropped 14.6% from the early 1990s. Bulk scattering was highly correlated with bulk nss SO42- in all flow regimes but the corresponding regression slopes varied significantly reflecting differential contributions to total scattering by associated aerosol components. Absorption by super-μm aerosol in transport from the NEUS versus AFR was similar although the super-μm aerosol size fraction accounted for a relatively greater contribution to total absorption in AFR flow. Significantly greater absorption Ångström exponents (AAEs) for AFR flow reflects the wavelength dependence of absorption by mineral aerosols; lower AAEs for NEUS flow is consistent with the dominance of absorption by combustion-derived aerosols. Higher AOD associated with transport from both the NEUS and AFR relative to oceanic background flow results in a top of atmosphere direct radiative forcing on the order of −1.6 to −2.5 W m−2, respectively, showing these aerosols drive cooling. The dominance of transport from the NEUS on an annual basis coupled with the corresponding decreases in anthropogenic nss SO42- aerosols since the early 1990s implies that emission reductions in the US account for a decline in atmospheric cooling over the western North Atlantic Ocean during this period.