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Eric E. Abrahamson Elizabeth Head Ira T. Lott Benjamin L. Handen Elliott J. Mufson Bradley T. Christian William E. Klunk Milos D. Ikonomovic 《Developmental neurobiology》2019,79(7):750-766
Down syndrome (DS) results in an overproduction of amyloid‐β (Aβ) peptide associated with early onset of Alzheimer's disease (AD). DS cases have Aβ deposits detectable histologically as young as 12–30 years of age, primarily in the form of diffuse plaques, the type of early amyloid pathology also seen at pre‐clinical (i.e., pathological aging) and prodromal stages of sporadic late onset AD. In DS subjects aged >40 years, levels of cortical Aβ deposition are similar to those observed in late onset AD and in addition to diffuse plaques involve cored plaques associated with dystrophic neurites (neuritic plaques), which are of neuropathological diagnostic significance in AD. The purpose of this review is to summarize and discuss findings from amyloid PET imaging studies of DS in reference to postmortem amyloid‐based neuropathology. PET neuroimaging applied to subjects with DS has the potential to (a) track the natural progression of brain pathology, including the earliest stages of amyloid accumulation, and (b) determine whether amyloid PET biomarkers predict the onset of dementia. In addition, the question that is still incompletely understood and relevant to both applications is the ability of amyloid PET to detect Aβ deposits in their earliest form. 相似文献
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During many infections, large numbers of effector CD8+ T cells are generated. After pathogen clearance, the majority of these cells undergo apoptosis, while the survivors differentiate into memory CD8+ T cells. Although loss of both Bim and Fas function dramatically increased antigen-specific CD8+ T cells in the lymph nodes following acute lymphocytic choriomeningitis virus (LCMV) infection, it was unclear whether they were pardoned effector or true memory CD8+ T cells. In this study, we demonstrate they are bona fide memory T cells as characterized by surface marker expression, cytokine production, homeostatic proliferation, and ability to clear a secondary challenge of pathogen. Loss of both Bim and Fas also increased the number of virus-specific CD4+ T cells found in the lymph nodes compared to the parental genotypes or wildtype mice. These studies illustrate that decreasing apoptosis increases the number of memory T cells and therefore could increase the efficacy of vaccines. 相似文献
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Effects of Moxonidine and Low‐Calorie Diet: Cardiometabolic Benefits from Combination of Both Therapies 下载免费PDF全文
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AMPK is an AMP-activated protein kinase that plays an important role in regulating cellular energy homeostasis. Metabolic
stress, such as heat shock and glucose starvation, causes an energy deficiency in the cell and leads to elevated levels of
intracellular AMP. This results in the phosphorylation and activation of AMPK. LKB1, a tumor suppressor, has been identified
as an upstream kinase of AMPK. We found that in response to treatment with 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside
(AICAR), the LKB1 deficient cancer cell line, HeLa, exhibited AMPK-α phosphorylation. This indicates the existence of an LKB1-independent
AMPK-α phosphorylation pathway. ATM is a protein that is deficient in the disease ataxia telangiectasia (A-T). We measured
the activation of AMPK by AICAR in the normal mouse embryo fibroblast cell line, A29, and the mouse cell line lacking the
ATM protein, A38. In A38 cells, the level of AICAR-induced AMPK-α phosphorylation was significantly lower than that found
in A29 cells. Furthermore, phosphorylation of AMPK in HeLa and A29 cells was inhibited by an ATM specific inhibitor, KU-55933.
Our results demonstrate that AICAR treatment could lead to phosphorylation of AMPK in an ATM-dependent and LKB1-independent
manner. Thus, ATM may function as a potential AMPK kinase in response to AICAR treatment. 相似文献
27.
Christian Frkjr‐Jensen Katie S. Kindt Rex A. Kerr Hiroshi Suzuki Katya Melnik‐Martinez Beate Gerstbreih Monica Driscol William R. Schafer 《Developmental neurobiology》2006,66(10):1125-1139
Voltage‐gated calcium channels (VGCCs) serve as a critical link between electrical signaling and diverse cellular processes in neurons. We have exploited recent advances in genetically encoded calcium sensors and in culture techniques to investigate how the VGCC α1 subunit EGL‐19 and α2/δ subunit UNC‐36 affect the functional properties of C. elegans mechanosensory neurons. Using the protein‐based optical indicator cameleon, we recorded calcium transients from cultured mechanosensory neurons in response to transient depolarization. We observed that in these cultured cells, calcium transients induced by extracellular potassium were significantly reduced by a reduction‐of‐function mutation in egl‐19 and significantly reduced by L‐type calcium channel inhibitors; thus, a main source of touch neuron calcium transients appeared to be influx of extracellular calcium through L‐type channels. Transients did not depend directly on intracellular calcium stores, although a store‐independent 2‐APB and gadolinium‐sensitive calcium flux was detected. The transients were also significantly reduced by mutations in unc‐36, which encodes the main neuronal α2/δ subunit in C. elegans. Interestingly, while egl‐19 mutations resulted in similar reductions in calcium influx at all stimulus strengths, unc‐36 mutations preferentially affected responses to smaller depolarizations. These experiments suggest a central role for EGL‐19 and UNC‐36 in excitability and functional activity of the mechanosensory neurons. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 相似文献
28.
The lack of a reliable and innocuous mark-recapture method has limited studies that would provide essential information for the management of commercial sea cucumbers. Tagging sea cucumbers is notoriously difficult because of their plastic nature and autolysis capacities. The markers that have so far been tested, mainly on or through the body wall, were either lost rapidly or had major drawbacks (e.g. suitable only for batch identification, requiring complex analysis, causing infections, necrosis, behavioural changes and mortality). The present study explored the efficacy of passive integrated transponder (PIT) tags for individually marking sea cucumbers by assessing retention rates and long-term side effects of tags inserted in previously unstudied tissues/organs. Individuals of the species Cucumaria frondosa were tagged in the body wall, aquapharyngeal bulb and at the base of the oral tentacles. They were monitored closely for evidence of stress, infection, change in feeding and spawning behaviour and tag retention rate. Implanting the tag in an oral tentacle to reach the hydrovascular system of the aquapharyngeal bulb achieved the best retention rates in full-size individuals: from a maximum of 92% after 30 days to 68% at the end of the experimental period (300 days). Efficacy was lower in smaller individuals (84% after 30 d and 42% after 300 d). Following a slight increase in cloacal movements for 15 h post tagging, no side effect was noted in sea cucumbers tagged in the aquapharyngeal bulb via the tentacles. Feeding and spawning behaviours were not affected and no signs of infections or abnormal cell development in the vicinity of the tags were observed. This study indicates that marking sea cucumbers with 8.2 mm long PIT tags implanted via the oral tentacle is an effective technique, yielding relatively high retention rates over long periods without any detectable physiological or behavioural effects. 相似文献
29.
While supertrees have been built for many vertebrate groups (notably birds, mammals and dinosaurs), invertebrates have attracted relatively little attention. The paucity of supertrees of arthropods is particularly surprising given their economic and ecological importance, as well as their overwhelming contribution to biodiversity. The absence of comprehensive archives of machine-readable source trees, coupled with the need for software implementing repeatable protocols for managing them, has undoubtedly impeded progress. Here we present a supertree of Achelata (spiny, slipper and coral lobsters) as a proof of concept, constructed using new supertree specific software (the Supertree Toolkit; STK) and following a published protocol. We also introduce a new resource for archiving and managing published source trees. Our supertree of Achelata is synthesised from morphological and molecular source trees, and represents the most complete species-level tree of the group to date. Our findings are consistent with recent taxonomic treatments, confirming the validity of just two families: Palinuridae and Scyllaridae; Synaxidae were resolved within Palinuridae. Monophyletic Silentes and Stridentes lineages are recovered within Palinuridae, and all sub-families within Scyllaridae are found to be monophyletic with the exception of Ibacinae. We demonstrate the feasibility of building larger supertrees of arthropods, with the ultimate objective of building a complete species-level phylogeny for the entire phylum using a divide and conquer strategy. 相似文献
30.
Albert L. Harting Michelle M. Barbieri Jason D. Baker Tracy A. Mercer Thea C. Johanos Stacie J. Robinson Charles L. Littnan Katie M. Colegrove Dave S. Rotstein 《Marine Mammal Science》2021,37(1):235-250
Identifying, assessing, and ranking the impact of individual threats is fundamental to the conservation and recovery of rare and endangered species. In this analysis, we quantify not only the frequency of specific causes-of-death (CODs) among Main Hawaiian Island (MHI) monk seals, but also assess the impact of individual CODs on the intrinsic growth rate, λ, of the MHI population. We used gross necropsy results, histopathology, and other evidence to assign probabilities of 11 COD types to each mortality and then used Monte Carlo sampling to evaluate the influence of each COD on λ. By right censoring realizations involving specific CODs, we were able to estimate λ (and its associated uncertainty) when CODs were selectively removed from influencing survival. Applying the analysis to all known and inferred deaths believed to have occurred 2004–2019, the CODs with the largest influence on λ were anthropogenic trauma, anthropogenic drowning, and protozoal disease. In aggregate, anthropogenic CODs had a larger effect on the growth rate than either natural or disease CODs. Possible bias associated with differential carcass detection, recovery, and COD classification are discussed. 相似文献