A Long Non-Coding RNA snaR Contributes to 5-Fluorouracil Resistance in Human Colon Cancer Cells

Several types of genetic and epigenetic regulation have been implicated in the development of drug resistance, one significant challenge for cancer therapy. Although changes in the expression of non-coding RNA are also responsible for drug resistance, the specific identities and roles of them remain to be elucidated. Long non-coding RNAs (lncRNAs) are a type of ncRNA (> 200 nt) that influence the regulation of gene expression in various ways. In this study, we aimed to identify differentially expressed lncRNAs in 5-fluorouracil-resistant colon cancer cells. Using two pairs of 5-FU-resistant cells derived from the human colon cancer cell lines SNU-C4 and SNU-C5, we analyzed the expression of 90 lncRNAs by qPCR-based profiling and found that 19 and 23 lncRNAs were differentially expressed in SNU-C4R and SNU-C5R cells, respectively. We confirmed that snaR and BACE1AS were downregulated in resistant cells. To further investigate the effects of snaR on cell growth, cell viability and cell cycle were analyzed after transfection of siRNAs targeting snaR. Down-regulation of snaR decreased cell death after 5-FU treatment, which indicates that snaR loss decreases in vitro sensitivity to 5-FU. Our results provide an important insight into the involvement of lncRNAs in 5-FU resistance in colon cancer cells.     

Effect of trapidil derivative AR 12456 on intracellular cholesterol homeostasis in human hepatoma cell line Hep G2

The effect of trapidil derivative AR12456 on intracellular cholesterol metabolism was investigated in human hepatoma cell line HepG2. AR12456 enhanced the uptake and degradation of¹²⁵I-LDL in a dose-dependent manner. The drug inhibited cholesterol synthesis and esterification without affecting cellular cholesterol content and bile acid synthesis; cholesterol efflux was slightly increased. These results show that the inhibition of cholesterol synthesis together with the enhanced expression of LDL receptors may partially explain the hypocholesterolemic activity of compound AR12456.     

Mapping carcass and meat quality QTL on Sus Scrofa chromosome 2 in commercial finishing pigs

Quantitative trait loci (QTL) affecting carcass and meat quality located on SSC2 were identified using variance component methods. A large number of traits involved in meat and carcass quality was detected in a commercial crossbred population: 1855 pigs sired by 17 boars from a synthetic line, which where homozygous (A/A) for IGF2. Using combined linkage and linkage disequilibrium mapping (LDLA), several QTL significantly affecting loin muscle mass, ham weight and ham muscles (outer ham and knuckle ham) and meat quality traits, such as Minolta-L* and -b*, ultimate pH and Japanese colour score were detected. These results agreed well with previous QTL-studies involving SSC2. Since our study is carried out on crossbreds, different QTL may be segregating in the parental lines. To address this question, we compared models with a single QTL-variance component with models allowing for separate sire and dam QTL-variance components. The same QTL were identified using a single QTL variance component model compared to a model allowing for separate variances with minor differences with respect to QTL location. However, the variance component method made it possible to detect QTL segregating in the paternal line (e.g. HAMB), the maternal lines (e.g. Ham) or in both (e.g. pHu). Combining association and linkage information among haplotypes improved slightly the significance of the QTL compared to an analysis using linkage information only.     

Childhood Environment and Mental Wellbeing at Age 60-64 Years: Prospective Evidence from the MRC National Survey of Health and Development

Background

Mental wellbeing, conceptualised as positive affect, life satisfaction and realisation of needs that contribute to psychological growth, captures more than the absence of mental ill health. Several nations now aim to monitor and improve mental wellbeing. Whilst many studies document associations between adverse childhood experiences and mental disorders in adulthood, possible links between childhood experiences and adult mental wellbeing have so far received less attention.

Methods

Using data from 1976 men and women in the MRC National Survey for Health and Development, we investigated prospective associations between childhood socioeconomic and psychosocial environments and the Warwick Edinburgh Mental Wellbeing Scale, designed to capture both hedonic and eudaimonic facets of wellbeing, at age 60-64.

Results

Whilst there was no evidence that childhood socioeconomic circumstances were related to later wellbeing independently of other childhood experiences, elements of childrearing and parenting, parental health and adjustment, and childhood illness were related. More advantaged socioeconomic position was associated with greater wellbeing but this did not explain the links between these childhood exposures and adult wellbeing, suggesting alternative explanatory pathways should be considered.

Conclusions

Childhood illness and family psychosocial environment are associated with mental wellbeing in early older age, with effects sizes that are larger or comparable to socioeconomic circumstances in adulthood. Initiatives to improve the nation’s mental wellbeing that include programmes targeted to supporting families and children may additionally have benefits that continue into older age.     

Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value

The diagnosis of rheumatoid arthritis (RA) is primarily based on clinical symptoms, so it is often difficult to diagnose RA in very early stages of the disease. A disease-specific autoantibody that could be used as a serological marker would therefore be very useful. Most autoimmune diseases are characterized by a polyclonal B-cell response targeting multiple autoantigens. These immune responses are often not specific for a single disease. In this review, the most important autoantibody/autoantigen systems associated with RA are described and their utility as a diagnostic and prognostic tool, including their specificity, sensitivity and practical application, is discussed. We conclude that, at present, the antibody response directed to citrullinated antigens has the most valuable diagnostic and prognostic potential for RA.     

Childhood socioeconomic position and objectively measured physical capability levels in adulthood: a systematic review and meta-analysis

Background

Grip strength, walking speed, chair rising and standing balance time are objective measures of physical capability that characterise current health and predict survival in older populations. Socioeconomic position (SEP) in childhood may influence the peak level of physical capability achieved in early adulthood, thereby affecting levels in later adulthood. We have undertaken a systematic review with meta-analyses to test the hypothesis that adverse childhood SEP is associated with lower levels of objectively measured physical capability in adulthood.

Methods and Findings

Relevant studies published by May 2010 were identified through literature searches using EMBASE and MEDLINE. Unpublished results were obtained from study investigators. Results were provided by all study investigators in a standard format and pooled using random-effects meta-analyses. 19 studies were included in the review. Total sample sizes in meta-analyses ranged from N = 17,215 for chair rise time to N = 1,061,855 for grip strength. Although heterogeneity was detected, there was consistent evidence in age adjusted models that lower childhood SEP was associated with modest reductions in physical capability levels in adulthood: comparing the lowest with the highest childhood SEP there was a reduction in grip strength of 0.13 standard deviations (95% CI: 0.06, 0.21), a reduction in mean walking speed of 0.07 m/s (0.05, 0.10), an increase in mean chair rise time of 6% (4%, 8%) and an odds ratio of an inability to balance for 5s of 1.26 (1.02, 1.55). Adjustment for the potential mediating factors, adult SEP and body size attenuated associations greatly. However, despite this attenuation, for walking speed and chair rise time, there was still evidence of moderate associations.

Conclusions

Policies targeting socioeconomic inequalities in childhood may have additional benefits in promoting the maintenance of independence in later life.     

An efficient model development strategy for bioprocesses based on neural networks in macroscopic balances: Part II

There is a need for efficient modeling strategies which quickly lead to reliable mathematical models that can be applied for design and optimization of (bio)-chemical processes. The serial gray box modeling strategy is potentially very efficient because no detailed knowledge is needed to construct the white box part of the model and because covenient black box modeling techniques like neural networks can be used for the black box part of the model. This paper shows for a typical biochemical conversion how the serial gray box modeling strategy can be applied efficiently to obtain a model with good frequency extrapolation properties. Models with good frequency extrapolation properties can be applied under dynamic conditions that were not present during the identification experiments. For a given application domain of a model, this property can be used to considerably reduce the number of identification experiments. The serial gray box modeling strategy is demonstrated to be successful for the modeling of the enzymatic conversion of penicillin G In the concentration range of 10-100 mM and temperature range of 298-335 K. Frequency extrapolation is shown by using only constant temperatures in the (batch) identification experiments, while the model can be used reliable with varying temperatures during the (batch) validation experiments. No reliable frequency extrapolation properties could be obtained for a black box model, and for a more knowledge-driven white box model reliable frequency extrapolation properties could only be obtained by incorporating more knowledge in the model. Copyright 1999 John Wiley & Sons, Inc.     

Risk factors for bacterial catheter colonization in regional anaesthesia

BACKGROUND: Although several potential risk factors have been discussed, risk factors associated with bacterial colonization or even infection of catheters used for regional anaesthesia are not very well investigated. METHODS: In this prospective observational trial, 198 catheters at several anatomical sites where placed using a standardized technique. The site of insertion was then monitored daily for signs of infection (secretion at the insertion site, redness, swelling, or local pain). The catheters were removed when clinically indicated (no or moderate postoperative pain) or when signs of potential infection occurred. After sterile removal they were prospectively analyzed for colonization, defined as > 15 colony forming units. RESULTS: 33 (16.7%) of all catheters were colonized, and 18 (9.1%) of these with additional signs of local inflammation. Two of these patients required antibiotic treatment due to superficial infections. Stepwise logistic regression analysis was used to identify factors associated with catheter colonization. Out of 26 potential factors, three came out as statistically significant. Catheter placement in the groin (odds-ratio and 95%-confidence interval: 3.4; 1.5-7.8), and repeated changing of the catheter dressing (odds-ratio: 2.1; 1.4-3.3 per removal) increased the risk for colonization, whereas systemic antibiotics administered postoperatively decreased it (odds ratio: 0.41; 0.12-1.0). CONCLUSION: Colonization of peripheral and epidural nerve catheter can only in part be predicted at the time of catheter insertion since two out of three relevant variables that significantly influence the risk can only be recorded postoperatively. Catheter localisation in the groin, removal of the dressing and omission of postoperative antibiotics were associated with, but were not necessarily causal for bacterial colonization. These factors might help to identify patients who are at increased risk for catheter colonization.     

Identification of signature and primers specific to genus <Emphasis Type="Italic">Pseudomonas</Emphasis> using mismatched patterns of 16S rDNA sequences

Background

Pseudomonas, a soil bacterium, has been observed as a dominant genus that survives in different habitats with wide hostile conditions. We had a basic assumption that the species level variation in 16S rDNA sequences of a bacterial genus is mainly due to substitutions rather than insertion or deletion of bases. Keeping this in view, the aim was to identify a region of 16S rDNA sequence and within that focus on substitution prone stretches indicating species level variation and to derive patterns from these stretches that are specific to the genus.

Results

Repeating elements that are highly conserved across different species of Pseudomonas were considered as guiding markers to locate a region within the 16S gene. Four repeating patterns showing more than 80% consistency across fifty different species of Pseudomonas were identified. The sub-sequences between the repeating patterns yielded a continuous region of 495 bases. The sub-sequences after alignment and using Shanon's entropy measure yielded a consensus pattern. A stretch of 24 base positions in this region, showing maximum variations across the sampled sequences was focused for possible genus specific patterns. Nine patterns in this stretch showed nearly 70% specificity to the target genus. These patterns were further used to obtain a signature that is highly specific to Pseudomonas. The signature region was used to design PCR primers, which yielded a PCR product of 150 bp whose specificity was validated through a sample experiment.

Conclusions

The developed approach was successfully applied to genus Pseudomonas. It could be tried in other bacterial genera to obtain respective signature patterns and thereby PCR primers, for their rapid tracking in the environmental samples.