35 research outputs found

    Climatic history of the northeastern United States during the past 3000 years

    Get PDF
    Many ecosystem processes that influence Earth system feedbacks – vegetation growth, water and nutrient cycling, disturbance regimes – are strongly influenced by multidecadal- to millennial-scale climate variations that cannot be directly observed. Paleoclimate records provide information about these variations, forming the basis of our understanding and modeling of them. Fossil pollen records are abundant in the NE US, but cannot simultaneously provide information about paleoclimate and past vegetation in a modeling context because this leads to circular logic. If pollen data are used to constrain past vegetation changes, then the remaining paleoclimate archives in the northeastern US (NE US) are quite limited. Nonetheless, a growing number of diverse reconstructions have been developed but have not yet been examined together. Here we conduct a systematic review, assessment, and comparison of paleotemperature and paleohydrological proxies from the NE US for the last 3000 years. Regional temperature reconstructions (primarily summer) show a long-term cooling trend (1000 BCE–1700 CE) consistent with hemispheric-scale reconstructions, while hydroclimate data show gradually wetter conditions through the present day. Multiple proxies suggest that a prolonged, widespread drought occurred between 550 and 750 CE. Dry conditions are also evident during the Medieval Climate Anomaly, which was warmer and drier than the Little Ice Age and drier than today. There is some evidence for an acceleration of the longer-term wetting trend in the NE US during the past century; coupled with an abrupt shift from decreasing to increasing temperatures in the past century, these changes could have wide-ranging implications for species distributions, ecosystem dynamics, and extreme weather events. More work is needed to gather paleoclimate data in the NE US to make inter-proxy comparisons and to improve estimates of uncertainty in reconstructions

    CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice

    Get PDF
    Neuroinflammation and microglial activation are significant processes in Alzheimer’s disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer’s disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer’s disease and other tau-mediated neurodegenerative diseases

    Inflammatory biomarkers in Alzheimer's disease plasma

    Get PDF
    Introduction:Plasma biomarkers for Alzheimer’s disease (AD) diagnosis/stratification are a“Holy Grail” of AD research and intensively sought; however, there are no well-established plasmamarkers.Methods:A hypothesis-led plasma biomarker search was conducted in the context of internationalmulticenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL;259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed.Results:Ten analytes showed significant intergroup differences. Logistic regression identified five(FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOε4 adjusted, optimally differentiated AD andCTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI(AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Twoanalytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71).Discussion:Plasma markers of inflammation and complement dysregulation support diagnosis andoutcome prediction in AD and MCI. Further replication is needed before clinical translatio

    The influence of winter temperatures on the annual radial growth of six northern range margin tree species.

    No full text
    Abstract This study explores the influence of temperature on the growth of six northern range margin (NRM) tree species in the Hudson River Valley (HRV). The HRV has excellent geographic and floristic qualities to study the influence of climate change on forested ecosystems. Indices of radial growth for three populations per species are developed and correlated against average minimum and maximum monthly temperatures from 1897 to 1994. Only positive correlations to temperature are considered for this analysis. Principal component analysis (PCA) is performed on chronologies over the entire HRV and at four subregions. PCA reveals a strong common signal among populations at subregional and regional scales. January temperatures most limit growth at the ecosystem level, supporting the hypothesis that winter temperatures may control vegetational ecotones. Surprisingly, growth of the oak-hickory ecosystem is most limited by January temperatures only in the southern half of the study region. Chestnut and white oak are the primary species driving the geographic pattern. As winter xylem embolism is a constant factor for ringporous species, snow cover and its interaction on fine root mortality may be the leading factors of the pattern of temperature sensitivity. Species-specific differences in temperature sensitivity are apparent. Atlantic white-cedar (AWC) and pitch pine are more sensitive to the entire winter season (December-March) while oak and hickory are most sensitive to January temperatures. AWC is most sensitive species to temperature. Chestnut and white oak in the HRV are more sensitive to winter temperature than red oak. Pignut hickory has the most unique response with significant relations to late growing season temperatures. Interestingly, AWC and pitch pine are sensitive to winter temperatures at their NRM while oak and hickory are not. Our results suggest that temperature limitations of growth may be species and phylogenetically specific. They also indicate that the influence of temperature on radial growth at species and ecosystem levels may operate differently at varying geographic scales. If these results apply broadly to other temperate regions, winter temperatures may play an important role in the terrestrial carbon cycle
    corecore