3,508 research outputs found
Laminar degeneration of frontal and temporal cortex in Parkinson disease dementia
To investigate cortical laminar degeneration in Parkinsonβs disease (PD) with dementia (PDD). Changes in density of Ξ±-synuclein-immunoreactive Lewy bodies (LB), Lewy neurites (LN), and Lewy grains (LG) together with surviving neurons, abnormally enlarged neurons (EN), vacuoles, and glial cell nuclei were measured across cortical laminae of frontal and temporal cortex in fifteen cases of PDD using quantitative methods and polynomial curve-fitting. Most frequently, LB and LN were distributed across all laminae, while LG were distributed in upper cortical laminae. Low densities of EN were present in most cases distributed across all cortical laminae. Densities of vacuoles and glia were greatest in upper and lower cortical laminae, respectively. In most gyri, there were no spatial correlations between the densities of LB, LN, and LG. Cortical degeneration of frontal and temporal lobes in PDD affects all cortical laminae. Laminar distributions may result from the spread of Ξ±-synuclein pathology from subcortical regions and subsequent spread via the cortico-cortical pathways. This spread may be a major factor in the development of dementia in PD
Theory of Multidimensional Solitons
We review a number of topics germane to higher-dimensional solitons in
Bose-Einstein condensates. For dark solitons, we discuss dark band and planar
solitons; ring dark solitons and spherical shell solitons; solitary waves in
restricted geometries; vortex rings and rarefaction pulses; and multi-component
Bose-Einstein condensates. For bright solitons, we discuss instability,
stability, and metastability; bright soliton engineering, including pulsed atom
lasers; solitons in a thermal bath; soliton-soliton interactions; and bright
ring solitons and quantum vortices. A thorough reference list is included.Comment: review paper, to appear as Chapter 5a in "Emergent Nonlinear
Phenomena in Bose-Einstein Condensates: Theory and Experiment," edited by P.
G. Kevrekidis, D. J. Frantzeskakis, and R. Carretero-Gonzalez
(Springer-Verlag
The T cell receptor/CD3 complex is composed of at least two autonomous transduction modules
Recent studies have demonstrated that the CD3-ΞΆ subunit of the T cell antigen receptor (TCR) complex is involved in signal transduction. However, the function of the remaining invariant subunits, CD3-Ξ³, -Ξ΄, and , is still poorly understood. To examine their role in TCR function, we have constructed TCR/CD3 complexes devoid of functional ΞΆ subunit and showed that they are still able to trigger the production of interleukin-2 in response to antigen or superantigen. These data, together with previous results, indicate that the TCR/CD3 complex is composed of at least two parallel transducing units, made of the Ξ³Ξ΄ and ΞΆ chains, respectively, Furthermore, the analysis of partially truncated ΞΆ chains has led us to individualize a functional domain that may have constituted the building block of most of the transducing subunits associated with antigen receptors and some Fc receptors
Evolution of Robustness to Noise and Mutation in Gene Expression Dynamics
Phenotype of biological systems needs to be robust against mutation in order
to sustain themselves between generations. On the other hand, phenotype of an
individual also needs to be robust against fluctuations of both internal and
external origins that are encountered during growth and development. Is there a
relationship between these two types of robustness, one during a single
generation and the other during evolution? Could stochasticity in gene
expression have any relevance to the evolution of these robustness? Robustness
can be defined by the sharpness of the distribution of phenotype; the variance
of phenotype distribution due to genetic variation gives a measure of `genetic
robustness' while that of isogenic individuals gives a measure of
`developmental robustness'. Through simulations of a simple stochastic gene
expression network that undergoes mutation and selection, we show that in order
for the network to acquire both types of robustness, the phenotypic variance
induced by mutations must be smaller than that observed in an isogenic
population. As the latter originates from noise in gene expression, this
signifies that the genetic robustness evolves only when the noise strength in
gene expression is larger than some threshold. In such a case, the two
variances decrease throughout the evolutionary time course, indicating increase
in robustness. The results reveal how noise that cells encounter during growth
and development shapes networks' robustness to stochasticity in gene
expression, which in turn shapes networks' robustness to mutation. The
condition for evolution of robustness as well as relationship between genetic
and developmental robustness is derived through the variance of phenotypic
fluctuations, which are measurable experimentally.Comment: 25 page
Relationship between bone density and bone metabolism in adolescent idiopathic scoliosis (AIS)
Ascending sensory motor polyradiculoneuropathy with cranial nerve involvement following administration of intrathecal methotrexate and intravenous cytarabine in a patient with acute myelogenous leukemia: a case report*
ACE2 gene expression is up-regulated in the human failing heart
BACKGROUND: ACE2 is a novel homologue of angiotensin converting enzyme (ACE). ACE2 is highly expressed in human heart and animal data suggest that ACE2 is an essential regulator of cardiac function in vivo. Since overactivity of the renin-angiotensin system contributes to the progression of heart failure, this investigation assessed changes in gene expression of ACE2, ACE, AT(1 )receptor and renin in the human failing heart. METHODS: The sensitive technique of quantitative reverse transcriptase polymerase chain reaction was used to determine the level of mRNA expression of ACE and ACE2 in human ventricular myocardium from donors with non-diseased hearts (n = 9), idiopathic dilated cardiomyopathy (IDC, n = 11) and ischemic cardiomyopathy (ICM, n = 12). Following logarithmic transformation of the data, a one-way analysis of variance was performed for each target gene followed by a Dunnett's test to compare the two disease groups IDC and ICM versus control. RESULTS: As anticipated, ACE mRNA was found to be significantly increased in the failing heart with a 3.1 and 2.4-fold up-regulation found in IDC and ICM relative to non-diseased myocardium. Expression of ACE2 mRNA was also significantly up-regulated in IDC (2.4-fold increase) and ICM (1.8-fold increase) versus non-diseased myocardium. No change in angiotensin AT(1 )receptor mRNA expression was found in failing myocardium and renin mRNA was not detected. CONCLUSIONS: These data suggest that ACE2 is up-regulated in human IDC and ICM and are consistent with the hypothesis that differential regulation of this enzyme may have important functional consequences in heart failure. This strengthens the hypothesis that ACE2 may be a relevant target for the treatment of heart failure and will hopefully spur further studies to clarify the functional effects in human myocardium of ACE2 derived peptides
High throughput mutagenesis for identification of residues regulating human prostacyclin (hIP) receptor
The human prostacyclin receptor (hIP receptor) is a seven-transmembrane G protein-coupled receptor (GPCR) that plays a critical role in vascular smooth muscle relaxation and platelet aggregation. hIP receptor dysfunction has been implicated in numerous cardiovascular abnormalities, including myocardial infarction, hypertension, thrombosis and atherosclerosis. Genomic sequencing has discovered several genetic variations in the PTGIR gene coding for hIP receptor, however, its structure-function relationship has not been sufficiently explored. Here we set out to investigate the applicability of high throughput random mutagenesis to study the structure-function relationship of hIP receptor. While chemical mutagenesis was not suitable to generate a mutagenesis library with sufficient coverage, our data demonstrate error-prone PCR (epPCR) mediated mutagenesis as a valuable method for the unbiased screening of residues regulating hIP receptor function and expression. Here we describe the generation and functional characterization of an epPCR derived mutagenesis library compromising >4000 mutants of the hIP receptor. We introduce next generation sequencing as a useful tool to validate the quality of mutagenesis libraries by providing information about the coverage, mutation rate and mutational bias. We identified 18 mutants of the hIP receptor that were expressed at the cell surface, but demonstrated impaired receptor function. A total of 38 non-synonymous mutations were identified within the coding region of the hIP receptor, mapping to 36 distinct residues, including several mutations previously reported to affect the signaling of the hIP receptor. Thus, our data demonstrates epPCR mediated random mutagenesis as a valuable and practical method to study the structurefunction relationship of GPCRs. Β© 2014 Bill et al
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