534 research outputs found
PrPSc complexity in different forms of Creutzfeldt-Jakob disease identified using biochemical approaches
Transmissible spongiform encephalopathies (TSEs) or prion diseases are a group of
fatal neurodegenerative diseases affecting humans and animal species. Prion diseases
are characterized by the conversion of the host encoded prion protein (PrPC) into a
disease-associated isoform (PrPSc), which (according to the prion hypothesis) is
thought to be the main component of the infectious agent. PrPSc has been
traditionally distinguished from PrPC by its biochemical properties, such as partial
resistance to proteolysis and detergent-insolubility. In the absence of a foreign
nucleic acid genome associated with prion diseases, efforts to provide a molecular
basis for the biological diversity of prions have focused on biochemical
characterization of PrPSc. In Creutzfeldt-Jakob disease (CJD) and other forms of
human prion disease, the biochemical characterization of PrPSc has been largely
restricted to the analysis of PK-resistant fragments of PrPSc (PrPres) by Western blot.
However, given recent findings on the complexity of PrPSc identified in laboratory
prion strains, PrPres analysis alone may not provide a complete description of PrPSc
present in CJD brains. For a more complete characterization of PrPSc in human prion
diseases, this study investigated biochemical properties of PrPSc in different forms of
CJD by employing approaches that differ in principle from conventional Western
blot analysis of PrPres. The novel biochemical approaches used in this study have
identified further complexity of PrPSc accumulated in CJD brains, not only between
different forms of CJD but also within single cases of individual disease entities. In
this study, the two biochemical criteria most frequently used to define PrPSc (3F4
epitope accessibility versus resistance to limited proteolysis) did not always correlate,
indicating probable non-uniform distribution of PK-sensitive isoform of PrPSc within
the same CJD brains. In variant CJD (vCJD) brains, the thalamic region, which is
characterized by distinct neuropathological features, could also be distinguished from
frontal cortex and cerebellum by the sedimentation profiles of PrPC and PrPSc on
sucrose step gradients. Moreover, the conformational stability of PrPSc was found not
to be uniform among human prion diseases and did not correlate with PrPres type or prion protein genotype. Taken together, the results from this study provide a more
complete description of PrPSc species occurring in CJD brains and contribute to a
fuller understanding of the agents and the disease processes involved in humans
RT-QuIC-based detection of alpha-synuclein seeding activity in brains of dementia with Lewy Body patients and of a transgenic mouse model of synucleinopathy
Production of Transgenic Cloned Miniature Pigs with Membrane-bound Human Fas Ligand (FasL) by Somatic Cell Nuclear Transfer
Cell-mediated xenograft rejection, including NK cells and CD8+ CTL, is a major obstacle in successful pig-to-human xenotransplantation. Human CD8+ CTL and NK cells display high cytotoxicity for pig cells, mediated at least in part by the Fas/FasL pathway. To prevent cell-mediated xenocytotoxicity, a membrane-bound form of human FasL (mFasL) was generated as an inhibitor for CTL and NK cell cytotoxicity that could not be cleaved by metalloproteinase to produce putative soluble FasL. We produced two healthy transgenic pigs harboring the mFasL gene via somatic cell nuclear transfer (SCNT). In a cytotoxicity assay using transgenic clonal cell lines and transgenic pig ear cells, the rate of CD8+ CTL-mediated cytotoxicity was significantly reduced in transgenic pig's ear cells compared with that in normal minipig fetal fibroblasts. Our data indicate that grafts of transgenic pigs expressing membrane-bound human FasL control the cellular immune response to xenografts, creating a window of opportunity to facilitate xenograft survival
Electronic topological transition in sliding bilayer graphene
We demonstrate theoretically that the topology of energy bands and Fermi
surface in bilayer graphene undergoes a very sensitive transition when
extremely tiny lateral interlayer shift occurs in arbitrary directions. The
phenomenon originates from a generation of effective non-Abelian vector
potential in Dirac Hamiltonian by the sliding motions. The characteristics of
the transition such as pair annihilations of massless Dirac fermions are
dictated by the sliding direction owing to a unique interplay between the
effective non-Abelian gauge fields and Berry's phases associated with massless
electrons. The transition manifests itself in various measurable quantities
such as anomalous density of states, minimal conductivity, and distinct Landau
level spectrum.Comment: title changed, an extended version for regular article format, 10
pages, 5 figure
A Mixed-effects Height-Diameter Model for Pinus densiflora Trees in Gangwon Province, Korea
A new mixed-effects model was developed that predicts individual-tree total height for Pinus densiflora trees in Gangwon province as a function of individual-tree diameter (cm). The mixed-effects model contains two random-effects parameters. Maximum likelihood estimation was used to fit the model to 560 height-diameter observations of individual trees measured throughout Gwangwon province in 2007 as part of the National Forest Inventory Program in Korea. The new model is an improvement over fixed effects models because it can be calibrated to a local area, such as an inventory plot or individual stand. The new model also appears to be an improvement over the Forest Resources Evaluation and Prediction Program for the ten calibration trees used in this study. An example is provided that describes how to estimate the random-effects parameters using ten calibration trees
Characteristics of Body Fat, Body Fat Percentage and Other Body Composition for Koreans from KNHANES IV
Accurate measurement of fat mass has become increasingly important with the increasing incidence of obesity. We assessed fat and muscle mass of Koreans with the Korea National Health and Nutrition Examination Survey IV (KNHANES IV). We studied 10,456 subjects (aged 20 to 85 yr; 4,476 men, 5,980 women). Fat and muscle mass were measured by dual-energy x-ray absorptiometry. Reference values of body compositions were obtained using the LMS method. The fat mass index (FMI, body fat mass/height2; kg/m2) of Korean men did not correlate with age (P = 0.452), but those of Korean women (P < 0.001) did. The ratio of percentage of fat in the trunk and legs was positively related with age in both the genders. The appendicular lean mass/height2 (kg/m2) of Korean men was negatively related to age (P < 0.001). In women, this ratio increased with age (P < 0.001). When we defined obesity according to the FMI classification, the rates of obesity were 6.1% (FMI > 9 kg/m2) in men and 2.7% (FMI > 13 kg/m2) in women. It is concluded that the muscle mass decreases and obesity increases with aging in Korean men, whereas both fat mass and obesity increase with aging in Korean women
The relative abundance of APOE and Aβ1-42 associated with abnormal prion protein differs between Creutzfeldt-Jakob disease subtypes
Aggregated
and protease-resistant mammalian prion protein (PrP<sup>Sc</sup>)
is the primary protein component of infectious prions.
Enriched PrP<sup>Sc</sup> preparations are often used to study the
mechanisms that underly prion disease. However, most enrichment procedures
are relatively nonspecific and tend to yield significant amounts of
non-PrP<sup>Sc</sup> components including various proteins that could
confound functional and structural studies. It is thus important to
identify these proteins and assess their potential relevance to prion
pathogenesis. Following proteinase K treatment and phosphotungstic
acid precipitation of brain homogenate, we have used mass spectrometry
to analyze the protein content of PrP<sup>Sc</sup> isolated from prion-infected
mice, multiple cases of sporadic Creutzfeldt-Jakob disease (sCJD),
and human growth hormone associated cases of iatrogenic CJD (iCJD).
Creatine kinase was the primary protein contaminant in all PrP<sup>Sc</sup> samples, while many of the other proteins identified were
also found in non-CJD controls, which suggests that they are not CJD
specific. Interestingly, the Alzheimer’s disease associated
peptide amyloid β 1–42 (Aβ1–42) was identified
in the majority of the sCJD cases as well as non-CJD age-matched controls,
while apoliprotein E was found in greater abundance in the sCJD cases.
By contrast, while some of the iCJD cases showed evidence of higher
molecular weight Aβ oligomers, monomeric Aβ1–42
peptide was not detected by immunoblot, and only one case had significant
levels of apolipoprotein E. Our data are consistent with the age-associated
deposition of Aβ1–42 in older sporadic CJD and non-CJD
patients and suggest that both apolipoprotein E and Aβ1–42
abundance can differ depending upon the type of CJD
Urachal Actinomycosis Mimicking a Urachal Tumor
A 26-year-old man presented with lower abdominal discomfort and a palpable mass in the right lower quadrant. An abdominal computed tomography (CT) scan revealed an abdominal wall mass that extended from the dome of the bladder. Fluorine-18 fluorodeoxyglucose (FDG) positron-emission tomography/CT (PET/CT) showed hypermetabolic wall thickening around the bladder dome area that extended to the abdominal wall and hypermetabolic mesenteric infiltration. Differential diagnosis included a urachal tumor with invasion into adjacent organs and chronic inflammatory disease. Partial cystectomy with abdominal wall mass excision was performed, and the final pathologic report was consistent with urachal actinomycosis
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