Proteomics studies of childhood pilocytic astrocytoma

Childhood pilocytic astrocytoma is the most frequent brain tumor affecting children. Proteomics analysis is currently considered a powerful tool for global evaluation of protein expression and has been widely applied in the field of cancer research. In the present study, a series of proteomics, genomics, and bioinformatics approaches were employed to identify, classify and characterize the proteome content of low-grade brain tumors as it appears in early childhood. Through bioinformatics database construction, protein profiles generated from pathological tissue samples were compared against profiles of normal brain tissues. Additionally, experiments of comparative genomic hybridization arrays were employed to monitor for genetic aberrations and sustain the interpretation and evaluation of the proteomic data. The current study confirms the dominance of MAPK pathway for the childhood pilocytic astrocytoma occurrence and novel findings regarding the ERK-2 expression are reported.     

The architecture of gene regulatory variation across multiple human tissues: the MuTHER study

While there have been studies exploring regulatory variation in one or more tissues, the complexity of tissue-specificity in multiple primary tissues is not yet well understood. We explore in depth the role of cis-regulatory variation in three human tissues: lymphoblastoid cell lines (LCL), skin, and fat. The samples (156 LCL, 160 skin, 166 fat) were derived simultaneously from a subset of well-phenotyped healthy female twins of the MuTHER resource. We discover an abundance of cis-eQTLs in each tissue similar to previous estimates (858 or 4.7% of genes). In addition, we apply factor analysis (FA) to remove effects of latent variables, thus more than doubling the number of our discoveries (1,822 eQTL genes). The unique study design (Matched Co-Twin Analysis--MCTA) permits immediate replication of eQTLs using co-twins (93%-98%) and validation of the considerable gain in eQTL discovery after FA correction. We highlight the challenges of comparing eQTLs between tissues. After verifying previous significance threshold-based estimates of tissue-specificity, we show their limitations given their dependency on statistical power. We propose that continuous estimates of the proportion of tissue-shared signals and direct comparison of the magnitude of effect on the fold change in expression are essential properties that jointly provide a biologically realistic view of tissue-specificity. Under this framework we demonstrate that 30% of eQTLs are shared among the three tissues studied, while another 29% appear exclusively tissue-specific. However, even among the shared eQTLs, a substantial proportion (10%-20%) have significant differences in the magnitude of fold change between genotypic classes across tissues. Our results underline the need to account for the complexity of eQTL tissue-specificity in an effort to assess consequences of such variants for complex traits.     

Rhinovirus infection induces cytotoxicity and delays wound healing in bronchial epithelial cells

Background

Human rhinoviruses (RV), the most common triggers of acute asthma exacerbations, are considered not cytotoxic to the bronchial epithelium. Recent observations, however, have questioned this knowledge. The aim of this study was to evaluate the ability of RV to induce epithelial cytotoxicity and affect epithelial repair in-vitro.

Methods

Monolayers of BEAS-2B bronchial epithelial cells, seeded at different densities were exposed to RV serotypes 1b, 5, 7, 9, 14, 16. Cytotoxicity was assessed chromatometrically. Epithelial monolayers were mechanically wounded, exposed or not to RV and the repopulation of the damaged area was assessed by image analysis. Finally epithelial cell proliferation was assessed by quantitation of proliferating cell nuclear antigen (PCNA) by flow cytometry.

Results

RV1b, RV5, RV7, RV14 and RV16 were able to induce considerable epithelial cytotoxicity, more pronounced in less dense cultures, in a cell-density and dose-dependent manner. RV9 was not cytotoxic. Furthermore, RV infection diminished the self-repair capacity of bronchial epithelial cells and reduced cell proliferation.

Conclusion

RV-induced epithelial cytotoxicity may become considerable in already compromised epithelium, such as in the case of asthma. The RV-induced impairment on epithelial proliferation and self-repair capacity may contribute to the development of airway remodeling.     

Biomimetic approaches to protein and gene delivery for tissue regeneration

Novel therapeutic strategies that promote wound healing seek to mimic the response of the body to wounding, to regenerate rather than repair injured tissues. Many synthetic or natural biomaterials have been developed for this purpose and are used to deliver wound therapeutics in a controlled manner that prevents unwanted and potentially harmful side-effects. Here, we review the natural and synthetic biomaterials that have been developed for protein and gene delivery to enhance tissue regeneration. Particular emphasis is placed on novel biomimetic materials that respond to environmental stimuli or release their cargo according to cellular demand. Engineering biomaterials to release therapeutic agents in response to physiologic signals mimics the natural healing process and can promote faster tissue regeneration and reduce scarring in severe acute or chronic wounds.     

Effect of breed and age on sexual behaviour of rams

The objective of this study was to highlight the problems that arise during the reproduction between thin-tailed rams and fat-tailed ewes. At the same time, particular emphasis laid on the influence of sheep breed, sheep age, time after ram introduction and day of the ewe estrus cycle on ram and ewe sexual behaviour. Rams were subjected to sexual performance tests by being individually exposed to 12 ewes for 3 h daily, 19 consecutive days. The 16 rams of the experiment were separated according to their age (9 and 21 months old) and breed (Chios and Karagouniki), and the 96 ewes of Chios fat-tailed breed, were divided by age (9 and 21 months old). The main characteristics of courtship behaviour, like sniffing, nudging, flehmen response and following were recorded and studied in detail. Mature Chios rams, which were the only one with previous experience of Chios ewes, exhibited higher rates of sexual interest per ewe than the other rams (P < 0.05). On the other hand, rams sniffed and nudged more young than mature ewes (P < 0.05), probably due to the fact that young ewes did not express intense symptoms of estrus. Young rams exhibited substandard sexual interest towards mature ewes, when they first came in contact with them (P < 0.05). In general, Karagouniki thin-tailed rams exhibited reduced rates of mating behaviour when they courted with Chios fat-tailed ewes in comparison with Chios rams (P < 0.05). Moreover, as the time after ram introduction passed, the frequency and duration of sexual behaviour components decreased (P < 0.001). Finally, the effect of the day of the experiment was only significant in the case of sniffing, which increased during the first 2 days and then declined and stabilized (P < 0.01). As it was demonstrated, ram age and ram breed played a fundamental role in the exhibition of sexual interest elements.