ApoB-100 <Emphasis Type="Italic">R3500Q</Emphasis> mutation in the Lebanese population: Prevalence and historical review of the literature

An interesting mutation affecting the Apo-B gene, R3500Q, is known to display variable geographical distribution in the world and is mostly implicated in the pathogenesis of Familial Hypercholesterolemia (FH). The aim of this study is to determine the prevalence of this mutation in the Lebanese population and compare it to the available international literature. DNA from 160 unrelated healthy donors from our HLA-bank was used and the ApoB genotype was determined using the CardioVascular Disease (CVD) StripAssay (this assay is based on a Polymerase Chain Reaction-Reverse Hybridization technique). The R3500Q mutation was not observed in the general Lebanese population. Since the mutation frequency is elevated in Central Europe and tends to decrease as one moves east and south, it disappears completely in the Mediterranean regions such as Spain, Turkey and Israel; therefore, it is rather expected to be absent in Lebanon as well. Our report adds a valuable piece of information regarding this mutation in an Arab country and paves the way for future research involving patients diagnosed with FH in order to assess the role of the R3500Q mutation in the development of this clinical entity.     

Airborne dust,bacteria, actinomycetes and fungi at a flourmill

A study was carried out on suspended dust, bacterial and fungal aerosols in a four-storey flourmill building located in Giza, Egypt. Airborne microorganisms were quantitatively isolated using liquid impinger and gravimetric samplers during the period from March 2004 to February 2005. Suspended dust varied from 1.96 to 16.3 mg m⁻³ and 0.69 to 1.8 mg m⁻³ in the indoor and outdoor environments, respectively. Suspended dust was significantly greater (P < 0.05) at bran package, double roller, purifiers and flour storage units in comparison to the outdoor reference site. The dust levels exceed the occupational exposure limit (OEL) of 0.5 mg m⁻³ for flour dust. Airborne microbial counts were found at median values, between sampling locations, ranged from 0 to >10⁴ CFU m⁻³. Gram-negative bacteria were found in small numbers (0–10² CFU m⁻³). The highest concentration of actinomycetes (>10³ CFU m⁻³) was detected in the storage unit. Airborne fungal counts were found at the median values, between sampling locations, varied from 10³ to 10⁴ CFU m⁻³. The counts of airborne bacteria and fungi were significantly greater (P < 0.05) at the purifiers and double roller mill units in comparison to the outdoor reference site using the liquid impinger sampler. Microbial levels associated with bulk deposited dust averaged between 10⁵ and 10⁶ CFU g⁻¹. Alcaligenes (5.4%) Pseudomonas (3.87%) and Enterobacter (3.1%) were the predominant Gram-negative species while Bacillus (29.4%) and Micrococci (13.9%) were the major components of Gram-positive bacteria. Aspergillus and Penicillium were the predominant fungal types indoor whereas Cladosporium (35.2%) and Aspergillus species (22.2%) were the predominant fungal types outdoor. A number of allergenic and toxigenic bioaerosols were found in the flourmill workplace.     

Polygenic in vivo validation of cancer mutations using transposons

The in vivo validation of cancer mutations and genes identified in cancer genomics is resource-intensive because of the low throughput of animal experiments. We describe a mouse model that allows multiple cancer mutations to be validated in each animal line. Animal lines are generated with multiple candidate cancer mutations using transposons. The candidate cancer genes are tagged and randomly expressed in somatic cells, allowing easy identification of the cancer genes involved in the generated tumours. This system presents a useful, generalised and efficient means for animal validation of cancer genes.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-014-0455-6) contains supplementary material, which is available to authorized users.     

Methylation status and protein expression of RASSF1A in breast cancer patients

Recently genetics and epigenetics alterations have been found to be characteristic of malignancy and hence can be used as targets for detection of neoplasia. RAS association domain family protein 1A (RASSF1A) gene hypermethylation has been a subject of interest in recent researches on cancer breast patients. The aim of the present study was to evaluate whether RASSF1A methylation status and RASSF1A protein expression are associated with the major clinico-pathological parameters. One hundred and twenty breast cancer Egyptian patients and 100-control subjects diagnosed with benign lesions of the breast were enrolled in this study. We evaluated RASSF1A methylation status in tissue and serum samples using Methyl specific PCR together with RASSF1A protein expression in tissues by immunohistochemistry. Results were studied in relation to known prognostic clinicopathological features in breast cancer. Frequency of RASSF1A methylation in tissues and serum were 70 and 63.3 % respectively and RASSF1A protein expression showed frequency of 46.7 %. There was an association between RASSF1A methylation in tissues, serum and loss of protein expression in tissues with invasive carcinoma, advanced stage breast cancer, L.N. metastasis, ER/PR and HER2 negativity. RASSF1A methylation in serum showed high degree of concordance with methylation in tissues (Kappa = 0.851, P < 0.001). RASSF1A hypermethylation in tissues and serum and its protein expression may be a valid, reliable and sensitive tool for detection and follow up of breast cancer patients.     

Spatial and Temporal Characteristics of Normal and Perturbed Vesicle Transport

Efficient intracellular transport is essential for healthy cellular function and structural integrity, and problems in this pathway can lead to neuronal cell death and disease. To spatially and temporally evaluate how transport defects are initiated, we adapted a primary neuronal culture system from Drosophila larval brains to visualize the movement dynamics of several cargos/organelles along a 90 micron axonal neurite over time. All six vesicles/organelles imaged showed robust bi-directional motility at both day 1 and day 2. Reduction of motor proteins decreased the movement of vesicles/organelles with increased numbers of neurite blocks. Neuronal growth was also perturbed with reduction of motor proteins. Strikingly, we found that all blockages were not fixed, permanent blocks that impeded transport of vesicles as previously thought, but that some blocks were dynamic clusters of vesicles that resolved over time. Taken together, our findings suggest that non-resolving blocks may likely initiate deleterious pathways leading to death and degeneration, while resolving blocks may be benign. Therefore evaluating the spatial and temporal characteristics of vesicle transport has important implications for our understanding of how transport defects can affect other pathways to initiate death and degeneration.     

An Evaluation of HIV Elite Controller Definitions within a Large Seroconverter Cohort Collaboration

Background

Understanding the mechanisms underlying viral control is highly relevant to vaccine studies and elite control (EC) of HIV infection. Although numerous definitions of EC exist, it is not clear which, if any, best identify this rare phenotype.

Methods

We assessed a number of EC definitions used in the literature using CASCADE data of 25,692 HIV seroconverters. We estimated proportions maintaining EC of total ART-naïve follow-up time, and disease progression, comparing to non-EC. We also examined HIV-RNA and CD4 values and CD4 slope during EC and beyond (while ART naïve).

Results

Most definitions classify ∼1% as ECs with median HIV-RNA 43–903 copies/ml and median CD4>500 cells/mm³. Beyond EC status, median HIV-RNA levels remained low, although often detectable, and CD4 values high but with strong evidence of decline for all definitions. Median % ART-naïve time as EC was ≥92% although overlap between definitions was low. EC definitions with consecutive HIV-RNA measurements <75 copies/ml with follow-up≥ six months, or with 90% of measurements <400 copies/ml over ≥10 year follow-up preformed best overall. Individuals thus defined were less likely to progress to endpoint (hazard ratios ranged from 12.5–19.0 for non-ECs compared to ECs).

Conclusions

ECs are rare, less likely to progress to clinical disease, but may eventually lose control. We suggest definitions requiring individuals to have consecutive undetectable HIV-RNA measurements for ≥ six months or otherwise with >90% of measurements <400 copies/ml over ≥10 years be used to define this phenotype.     

The Association of Genotype-Based Inbreeding Coefficient with a Range of Physical and Psychological Human Traits

Across animal species, offspring of closely related mates exhibit lower fitness, a phenomenon called inbreeding depression. Inbreeding depression in humans is less well understood because mating between close relatives is generally rare and stigmatised, confounding investigation of its effect on fitness-relevant traits. Recently, the availability of high-density genotype data has enabled quantification of variation in distant inbreeding in ‘outbred’ human populations, but the low variance of inbreeding detected from genetic data in most outbred populations means large samples are required to test effects, and only a few traits have yet been studied. However, it is likely that isolated populations, or those with a small effective population size, have higher variation in inbreeding and therefore require smaller sample sizes to detect inbreeding effects. With a small effective population size and low immigration, Northern Finland is such a population. We make use of a sample of ∼5,500 ‘unrelated’ individuals in the Northern Finnish Birth Cohort 1966 with known genotypes and measured phenotypes across a range of fitness-relevant physical and psychological traits, including birth length and adult height, body mass index (BMI), waist-to-hip ratio, blood pressure, heart rate, grip strength, educational attainment, income, marital status, handedness, health, and schizotypal features. We find significant associations in the predicted direction between individuals'' inbreeding coefficient (measured by proportion of the genome in runs of homozygosity) and eight of the 18 traits investigated, significantly more than the one or two expected by chance. These results are consistent with inbreeding depression effects on a range of human traits, but further research is needed to replicate and test alternative explanations for these effects.