116 research outputs found
Adiponectin: Serum-saliva associations and relations with oral and systemic markers of inflammation
This study addresses gaps in our understanding about the validity and utility of using salivary adiponectin to
index serum adiponectin levels. Matched blood and saliva samples were collected on a single occasion from
healthy adults (n=99; age 18–36 years, 53% male). Serum and saliva was assayed for adiponectin and
inflammatory cytokines (IL-1β, IL-6, IL-8, TNFα), and saliva was also assayed for markers of blood
contamination (transferrin), total protein (salivary flow rate) and matrix metalloproteinase-8 (MMP-8). We
examined the extent to which salivary adiponectin was associated with serum adiponectin, and the influence of
potential confounders on the serum-saliva correlation, including age, sex, body mass index, and markers of
inflammation, oral health, salivary blood contamination, and flow rate. Findings revealed a modest serum-saliva
association for adiponectin, and strong positive associations between salivary adiponectin and salivary levels of
inflammatory cytokines, MMP-8, transferrin, and total protein. By contrast, salivary adiponectin was not related
to serum levels of inflammatory activity. The magnitude of the serum-saliva association was strengthened when
controlling for total protein in saliva, blood leakage into oral fluid, salivary inflammatory cytokines, and MMP-8.
The pattern of findings extends our understanding of salivary adiponectin and its potential use as an index of
circulating adiponectin levels
Fluctuations of company yearly profits versus scaled revenue: Fat tail distribution of Levy type
We analyze annual revenues and earnings data for the 500 largest-revenue U.S.
companies during the period 1954-2007. We find that mean year profits are
proportional to mean year revenues, exception made for few anomalous years,
from which we postulate a linear relation between company expected mean profit
and revenue. Mean annual revenues are used to scale both company profits and
revenues. Annual profit fluctuations are obtained as difference between actual
annual profit and its expected mean value, scaled by a power of the revenue to
get a stationary behavior as a function of revenue. We find that profit
fluctuations are broadly distributed having approximate power-law tails with a
Levy-type exponent , from which we derive the associated
break-even probability distribution. The predictions are compared with
empirical data.Comment: 6 pages, 6 figure
MicroRNA-138 is a potential regulator of memory performance in humans
Genetic factors underlie a substantial proportion of individual differences in cognitive functions in humans, including processes related to episodic and working memory. While genetic association studies have proposed several candidate "memory genes," these currently explain only a minor fraction of the phenotypic variance. Here, we performed genome-wide screening on 13 episodic and working memory phenotypes in 1318 participants of the Berlin Aging Study II aged 60 years or older. The analyses highlight a number of novel single nucleotide polymorphisms (SNPs) associated with memory performance, including one located in a putative regulatory region of microRNA (miRNA) hsa-mir-138-5p (rs9882688, P-value = 7.8 x 10(-9)). Expression quantitative trait locus analyses on next-generation RNA-sequencing data revealed that rs9882688 genotypes show a significant correlation with the expression levels of this miRNA in 309 human lymphoblastoid cell lines (P-value = 5 x 10(-4)). In silico modeling of other top-ranking GWAS signals identified an additional memory-associated SNP in the 3' untranslated region (3' UTR) of DCP1B, a gene encoding a core component of the mRNA decapping complex in humans, predicted to interfere with hsa-mir-138-5p binding. This prediction was confirmed in vitro by luciferase assays showing differential binding of hsa-mir-138-5p to 3' UTR reporter constructs in two human cell lines (HEK293: P-value = 0.0470; SH-SY5Y: P-value = 0.0866). Finally, expression profiling of hsa-mir-138-5p and DCP1B mRNA in human post-mortem brain tissue revealed that both molecules are expressed simultaneously in frontal cortex and hippocampus, suggesting that the proposed interaction between hsa-mir-138-5p and DCP1B may also take place in vivo. In summary, by combining unbiased genome-wide screening with extensive in silico modeling, in vitro functional assays, and gene expression profiling, our study identified miRNA-138 as a potential molecular regulator of human memory function
The introduction of the Cancer Research UK Stratified Medicine Programme 2 (CRUK SMP2) in North East England; lessons learned and experience gained
Introduction: The CRUK SMP2 programme was set-up to evaluate
the feasibility of performing large scale molecular analysis within the
NHS on the (often small) diagnostic biopsies obtained in NSCLC. The
results are used to allocate patients to an appropriate molecular therapy
within the “umbrella” MATRIX trial. Newcastle opened SMP2 on
01/10/2014. Here we report our first year’s experience.
Methods: NSCLC patients with PS 0–2 were consented onto the CRUK
SMP2. Matched residual diagnostic tissue and blood were sent to All
Wales Genetics Laboratory, Cardiff. Samples with >70ng DNA were
assessed for 28 oncogenes using Next Genuine Sequencing on the Illumina
SMP2 panel.
Results: 116 patients were consented from 6/10/14–1/10/15 referred
from 12 oncologists. The data on patient/sample flow is shown in Fig
1. Median survival was 161 days from consent. The 1st sample was
sent to Cardiff on 28/1/15 as the Illumina panel was undergoing fi-
nal validation. 50 samples have been sent; 11 had insufficient DNA;
these samples had lower cell number (but with no impact of necrosis/tumour
proportion); The most commonly altered gene was K-Ras
(13 of 22 adenocarcinomas). Only 2 patients with results from >25
of the 28 genes had no tier 1 or 2 ie potentially treatable molecular
abnormalities. The median time from consent to result was 109 days
(range 45–250) with delays occurring throughout the pathway.
Conclusion: Patients and oncologists are keen to be involved in
molecular profiling; but patients need to be consented early to allow
results to guide therapy. Prioritisation of samples is key. Not all
samples are suitable for analysis due to small cell number or low tumour
proportion. Molecular analysis may require extra resource in
pathology, if it is to become standard of care. The first 4 patients to
start treatment on MATRIX were enrolled from 27/8/15 in Newcastle.
Disclosure: All authors have declared no conflicts of interest
A Novel Multiplex Cell Viability Assay for High-Throughput RNAi Screening
Cell-based high-throughput RNAi screening has become a powerful research tool in addressing a variety of biological questions. In RNAi screening, one of the most commonly applied assay system is measuring the fitness of cells that is usually quantified using fluorescence, luminescence and absorption-based readouts. These methods, typically implemented and scaled to large-scale screening format, however often only yield limited information on the cell fitness phenotype due to evaluation of a single and indirect physiological indicator. To address this problem, we have established a cell fitness multiplexing assay which combines a biochemical approach and two fluorescence-based assaying methods. We applied this assay in a large-scale RNAi screening experiment with siRNA pools targeting the human kinome in different modified HEK293 cell lines. Subsequent analysis of ranked fitness phenotypes assessed by the different assaying methods revealed average phenotype intersections of 50.7±2.3%–58.7±14.4% when two indicators were combined and 40–48% when a third indicator was taken into account. From these observations we conclude that combination of multiple fitness measures may decrease false-positive rates and increases confidence for hit selection. Our robust experimental and analytical method improves the classical approach in terms of time, data comprehensiveness and cost
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