277 research outputs found
Alpha-synuclein (SNCA) polymorphisms exert protective effects on memory after mild traumatic brain injury
Problems with attention and short-term learning and memory are commonly reported after mild traumatic brain injury (mTBI). Due to the known relationships between Îą-synuclein (SNCA), dopaminergic transmission, and neurologic deficits, we hypothesized that SNCA polymorphisms might be associated with cognitive outcome after mTBI. A cohort of 91 mTBI patients one month after injury and 86 healthy controls completed a series of cognitive tests assessing baseline intellectual function, attentional function, and memory, and was genotyped at 13 common single nucleotide polymorphisms (SNPs) in the SNCA gene. Significant differences in two memory measures (p = 0.001 and 0.002), but not baseline intellectual function or attentional function tasks, were found between the mTBI group and controls. A highly significant protective association between memory performance and SNCA promoter SNP rs1372525 was observed in the mTBI patients (p = 0.006 and 0.029 for the long and short delay conditions of the California Verbal Learning Tests, respectively), where the presence of at least one copy of the A (minor) allele was protective after mTBI. These results may help elucidate the pathophysiology of cognitive alterations after mTBI, and thus warrant further investigation
Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis
Most tumors exhibit increased glucose metabolism to lactate, however, the extent to which glucose-derived metabolic fluxes are used for alternative processes is poorly understood [1, 2]. Using a metabolomics approach with isotope labeling, we found that in some cancer cells a relatively large amount of glycolytic carbon is diverted into serine and glycine metabolism through phosphoglycerate dehydrogenase (PHGDH). An analysis of human cancers showed that PHGDH is recurrently amplified in a genomic region of focal copy number gain most commonly found in melanoma. Decreasing PHGDH expression impaired proliferation in amplified cell lines. Increased expression was also associated with breast cancer subtypes, and ectopic expression of PHGDH in mammary epithelial cells disrupted acinar morphogenesis and induced other phenotypic alterations that may predispose cells to transformation. Our findings show that the diversion of glycolytic flux into a specific alternate pathway can be selected during tumor development and may contribute to the pathogenesis of human cancer.National Institutes of Health (U.S.)National Cancer Institute (U.S.)Smith Family FoundationDamon Runyon Cancer Research FoundationBurroughs Wellcome Fun
Brane-World Gravity
The observable universe could be a 1+3-surface (the "brane") embedded in a
1+3+\textit{d}-dimensional spacetime (the "bulk"), with Standard Model
particles and fields trapped on the brane while gravity is free to access the
bulk. At least one of the \textit{d} extra spatial dimensions could be very
large relative to the Planck scale, which lowers the fundamental gravity scale,
possibly even down to the electroweak ( TeV) level. This revolutionary
picture arises in the framework of recent developments in M theory. The
1+10-dimensional M theory encompasses the known 1+9-dimensional superstring
theories, and is widely considered to be a promising potential route to quantum
gravity. At low energies, gravity is localized at the brane and general
relativity is recovered, but at high energies gravity "leaks" into the bulk,
behaving in a truly higher-dimensional way. This introduces significant changes
to gravitational dynamics and perturbations, with interesting and potentially
testable implications for high-energy astrophysics, black holes, and cosmology.
Brane-world models offer a phenomenological way to test some of the novel
predictions and corrections to general relativity that are implied by M theory.
This review analyzes the geometry, dynamics and perturbations of simple
brane-world models for cosmology and astrophysics, mainly focusing on warped
5-dimensional brane-worlds based on the Randall--Sundrum models. We also cover
the simplest brane-world models in which 4-dimensional gravity on the brane is
modified at \emph{low} energies -- the 5-dimensional Dvali--Gabadadze--Porrati
models. Then we discuss co-dimension two branes in 6-dimensional models.Comment: A major update of Living Reviews in Relativity 7:7 (2004)
"Brane-World Gravity", 119 pages, 28 figures, the update contains new
material on RS perturbations, including full numerical solutions of
gravitational waves and scalar perturbations, on DGP models, and also on 6D
models. A published version in Living Reviews in Relativit
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