An Ode For an Anniversary of Music on S. Cecilia’s Day

Oldham, John; Brooks, Harold F.; Selden, Raman

doi:10.1093/oseo/instance.00024898

Cited by 4 publications

(5 citation statements)

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“…ACAT-inhibitors have slowed the development of amyloid plaques while MAPK1-inhibition is hypothesized to reduce hyperphosphorylation of the tau proteins which can lead to aggregation [59]. While fibroblast growth factor 12 (FGF12) and metallo-beta-lactamase domain-containing protein (MBLAC) are expressed in the human brain, they have not been linked to either the structural or pathological function of tau protein [60][61][62]. Spectrin beta chain (SPBT2) interacts with alpha-synuclein, one of the hallmarks of another neurodegenerative disease, Parkinson's [63].…”

Section: Expression Of Microtubule-associated Protein Taumentioning

confidence: 99%

Proteomic Atlas of the Human Brain in Alzheimer’s Disease

McKetney¹,

Runde²,

Hebert³

et al. 2019

J. Proteome Res.

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The brain represents one of the most divergent and critical organs in the human body. Yet, it can be afflicted by a variety of neurodegenerative diseases specifically linked to aging, about which we lack a full biomolecular understanding of onset and progression, such as Alzheimer's Disease (AD). Here we provide a proteomic resource comprising nine anatomically distinct sections from three aged individuals, across a spectrum of disease progression, categorized by quantity of neurofibrillary tangles. Using state-of-the-art mass spectrometry, we identify a core brain proteome that exhibits only small variance in expression, accompanied by a group of proteins that are highly differentially expressed in individual sections and broader regions. AD affected tissue exhibited slightly elevated levels of tau protein with similar relative expression to factors associated with the AD pathology. Substantial differences were identified between previous proteomic studies of mature adult brains and our aged cohort. Our findings suggest considerable value in examining specifically the brain proteome of aged human populations from a multiregional perspective. This resource can serve as a guide, as well as a point of reference for how specific regions of the brain are affected by aging and neurodegeneration.

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Section: Expression Of Microtubule-associated Protein Taumentioning

confidence: 99%

Proteomic Atlas of the Human Brain in Alzheimer’s Disease

McKetney¹,

Runde²,

Hebert³

et al. 2019

J. Proteome Res.

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“…32. The dPTEN alleles used are dPTEN dj189 (19) and dPTEN 117 (37). Both are presumably null alleles.…”

mentioning

confidence: 99%

Living with Lethal PIP3 Levels: Viability of Flies Lacking PTEN Restored by a PH Domain Mutation in Akt/PKB

Stocker

Andjelković

Oldham

et al. 2002

Science

191

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The phosphoinositide phosphatase PTEN is mutated in many human cancers. Although the role of PTEN has been studied extensively, the relative contributions of its numerous potential downstream effectors to deregulated growth and tumorigenesis remain uncertain. We provide genetic evidence in Drosophila melanogaster for the paramount importance of the protein kinase Akt [also called protein kinase B (PKB)] in mediating the effects of increased phosphatidylinositol 3,4,5-trisphosphate (PIP3) concentrations that are caused by the loss of PTEN function. A mutation in the pleckstrin homology (PH) domain of Akt that reduces its affinity for PIP3 sufficed to rescue the lethality of flies devoid of PTEN activity. Thus, Akt appears to be the only critical target activated by increased PIP3 concentrations in Drosophila.Mutations in the tumor suppressor gene PTEN (the phosphatase and tensin homolog on chromosome 10) are frequent in glioblastomas, endometrial carcinoma, melanomas, and prostate cancer (1). Furthermore, two dominant hamartoma syndromes, Cowden disease and Bannayan-Zonana syndrome, are linked to germ line mutations in PTEN (1). The PTEN protein carries a phosphatase domain resembling those of dual-specificity protein phosphatases (2-4 ). Although it can dephosphorylate protein substrates such as focal adhesion kinase (5) and the adapter protein Shc (6), PTEN's predominant enzymatic activity appears to be the dephosphorylation of phosphoinositides at the D3 position. Because PTEN uses the second messenger PIP3 as a substrate, PTEN antagonizes the function of phosphatidylinositol-3 kinase (PI3K) (7,8). Immortalized mouse embryonic fibroblasts or embryonic stem cells lacking PTEN function show an approximately twofold increase in PIP3 concentrations (9, 10). PIP3 interacts with a wide variety of PH domain-containing proteins, including the serine-threonine kinases Akt (also called PKB) and phosphoinositide-dependent kinase 1 (PDK1), Btk family tyrosine kinases, guanine nucleotide exchange factors for the Rho and Arf families of small guanosine triphosphatases, and phospholipase C␥ (11,12). The plethora of proteins that are potentially regulated by PIP3 provides widespread signaling potential for this lipid second messenger.Genetic analyses in model organisms have implicated PTEN as a negative regulator of insulin receptor signaling. In the nematode Caenorhabditis elegans, PTEN antagonizes the activity of the PI3K AGE-1 in the regulation of metabolism, development, and life span (13-16). In the fruit fly Drosophila melanogaster, PTEN counteracts signaling downstream of the insulin receptor to control cellular growth (17-19). There are, however, Transfected cells were starved for 24 hours before stimulation with insulin for the indicated time periods, and dAkt kinase activity was determined (44). The activity of wild-type dAkt from unstimulated cells was considered to be relative activity ϭ 1.

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“…In the foregoing studies (FIGURE 3), and in earlier studies from this laboratory," it has become apparent that the addition of electron donors is followed by the rapid appearance of a Type I1 spectrum. Because of the above observations, which strongly suggest that this spectral shift reflects the hydroxylation of endogenous steroid substrates, we have reinvestigated the conditions for maximal rates of cholesterol SCC and DOC hydroxylation.…”

Section: Introductionmentioning

confidence: 71%