The "golden age" of biotechnology in Europe

This is a short paper reviewing the most important presentations at the European Biotechnology Congress 2011 which was held in Istanbul between the 28th of September and the 1st of October 201

Alterations in protein P53 expression during the development of pressure overload-induced left ventricular hypertrophy in rats

The relation between myocardial structural and functional changes and p53 proteins during the development of left ventricular hypertrophy (LVH) has not yet been reported. The purpose of this study was to determine whether p53 protein expression is altered during development of LVH, induced by pressure overload. LVH was induced in 80 male Wistar adult rats by abdominal aortic banding (AAB) and was monitored at the 10th, 15th, 20th, 25th, 35th and 45th post-operation days by echocardiography and validated by postmortem examination. Sham operated (SO) rats (n=60) went the same operation without banding. The expression of p53 protein in the nuclear and cytoplasmic extracts from left ventricular tissue from AAB and SO rats were analyzed by immunoblotting at each of the pointed days. Relative to SO, echo-left ventricular mass-to-tibia length (LVM/TL) ratio in AAB increased progressively on the 10th and the 15th day. On the 20th day we observed a short lasting regression of LVH, followed by a new marked increase on the 25th and 35th day; then there was presented a plateau. Relative to SO the changes in LV%FS (77% ± 2.2 %) in AAB rats remained at the same level throughout the studied period without significant differences in body weight or tibia length (TL). Results from echocardiography were validated by necropsy. Echo LVM/TL correlated significantly with actual heart weight-to-tibia length ratio (r=0.69, P<0.0001, n=140). The level of p53 protein expression in the nuclear extracts from LV tissues obtained from AAB rats increased significantly by 77%, 78%, 35% and 63% at day 10th, 20th, 35th and 45th, respectively compared with SO, and returned to SO levels by day 15th and 25th post-operation. The highest level of p53 protein in the nuclear extracts from LV tissues obtained from AAB rats was determined on 20th day concomitant with significant reduction of the actual heart mass in the group with AAB rats, compared with the same groups on the other days. In the cytozol the expression of p53 was always higher in the SO, compared with AAB groups. Furthermore, the level of p53 protein in the nuclear extracts from AAB rats significantly correlated with the actual heart weight during the studied period (r= -0.59, P<0.0001, n=60). Following the development of LVH over a relatively long period of time and providing the changes in short intervals, it was found a short lasting regression during ongoing pressure overload concomitant with significantly increased expression of p53 protein in the nuclear extracts from AAB rats. This study adds new important concepts for the time dependency of LVH and suggests that p53 protein may modulate the adaptive growth of pressure overload induced LVH

Laser light scattering applications in biotechnology

Recent advancement of laser light scattering applications in biotechnology are reviewed with emphasis on their use in the biopharmaceutical industry. Light scattering methods have been used to date to characterize biomolecules in solution. They can provide information about the size and conformation of proteins and their aggregation state as well as their ability to crystallise. In addition, modern light scattering instrumentation is becoming method of choice for studying macromolecular interactions. Interactions between macromolecules such as proteins and nucleic acids mediate fundamental processes and their modulation has led to new strategies for developing therapeutics. Light scattering approaches offer significant advantage to other approaches for studying molecular interactions. Compared with other techniques, light scattering is very quick, uses minimal sample quantities, allows recovery of the sample and does nor require derivatisation

Nothing in excess - lessons learned from the expression of high-mobility group proteins type A in non-cancer and cancer cells

High-mobility group A (HMGA) proteins are major transcription regulators which are abundantly and ubiquitously expressed in undifferentiated cells but present at a low level in somatic cells of adult organisms. Up-regulation of HMGA expression is a frequent finding in cancer, either via direct stimulation of expression by constitutively expressed proto-oncogenic factors such as MYC and JUN or by rearrangements rendering the expression of the HMGA proteins not suppressible by inhibitory factors such as miRNAs. Rearrangements of the HMGA genomic loci resulting in disabling of the control mechanisms of their expression are often seen in tumours of various origin. A direct relationship between the level of expression of HMGA in mitochondria and the level of accumulation of oxidative damage in cancer cells has been recently noted. On the other hand, mammalian cells deficient in HMGA1 expression are also deficient in utilization of glucose and show the impairment in expression of the insulin receptor and the high levels of oxidative damage of DNA characteristic of diabetes type 2 and the related condition metabolic syndrome. Insulin resistance and metabolic syndrome could be viewed as a premalignant state in which DNA damage is slowly accumulating until the repair machinery of the cell cannot withstand the constant oxidative barrage and surrenders to neoplastic transformation

Effect of liquid nitrogen pre-treatment on various types of wool waste fibres for biogas production

This study investigated the role of liquid nitrogen (LN2) in increasing microbial accessibility of wool proteins for biogas production. It involves a mechanical size reduction of four different types of raw wool fibres, namely, Blackface, Bluefaced Leicester, Texel and Scotch Mule, in presence of liquid nitrogen, followed by the determination of the methane production potential of the pre-treated wool fibres. The highest methane yield, 157.3 cm3 g−1 VS, was obtained from pre-treated Scotch mule wool fibre culture, and represented more than 80% increase when compared to the yield obtained from its raw equivalent culture. The increase in biogas yield was attributed to the effectiveness of LN2 in enhancing particle size reduction and the consequent increase in wool solubility and bioavailability. Results also showed that LN2 pre-treatment can enhance size reduction but has limited effect on the molecular structure. The study also showed that the biogas potential of waste wool fibres varies with the type and source of wool

Repair, abort, ignore? Strategies for dealing with UV damage

DNA repair is a prominent member of the nuclear transactions triad (replication, transcription, and repair). Sophisticated mechanisms govern the cellular process of decision-making (to repair or not to repair, to proceed with cell cycle or not and, eventually, to let the cell survive or die) and the temporal and spatial distribution of the DNA repair activities. UV radiation is a very common and virtually unavoidable mutagen whose carcinogenic potential seems to accumulate over time. Various strategies have been developed to avoid or decrease UV damage to cellular DNA, based on prevention of exposure as well as on post-irradiation measures. It is, however, important to acknowledge that the individual capacity for DNA repair varies during the life of the individual and must, therefore, be assessed so as to determine whether the individual is coping with environmental UV damage. Assessment of individual repair capacity might greatly modify the existing therapeutic strategies for common cancers and ought to become a routine part of health prophylaxis

Differential genetic advantages in youth and in aging, or how to die healthy

Human society ages at a steady rate, that is, the proportion of adult and elderly individuals increases constantly because of improved living conditions and the advances in medical care. This means that very soon the tradeoff between the advantages in old age conferred by alleles disadvantageous or neutral in young age would begin to show, providing the fascinating opportunity of studying the interplay between genetic factors and environment outside the framework of reproductive capacity and in the unique milieu of the aging cell. Being healthy and/or health-conscious in youth does not guarantee for successful aging or even that the person would live up to the average life expectancy of the population. Therefore, successful aging and longevity are related to a healthy-conscious attitude to a degree only. The present paper reviews the basic genetic and evolutionary mechanisms which have operated during human history so as to ensure survival of humankind and the possible factors preventing or contributing to successful aging

ATM in focus:a damage sensor and cancer target

The ability of a cell to conserve and maintain its native DNA sequence is fundamental for the survival and normal functioning of the whole organism and protection from cancer development. Here we review recently obtained results and current topics concerning the role of the ataxia-telangiectasia mutated (ATM) protein kinase as a damage sensor and its potential as therapeutic target for treating cancer. This monograph discusses DNA repair mechanisms activated after DNA double-strand breaks (DSBs), i.e. non-homologous end joining, homologous recombination and single strand annealing and the role of ATM in the above types of repair. In addition to DNA repair, ATM participates in a diverse set of physiological processes involving metabolic regulation, oxidative stress, transcriptional modulation, protein degradation and cell proliferation. Full understanding of the complexity of ATM functions and the design of therapeutics that modulate its activity to combat diseases such as cancer necessitates parallel theoretical and experimental efforts. This could be best addressed by employing a systems biology approach, involving mathematical modelling of cell signalling pathways

Some problems and errors in cytogenetic biodosimetry

Human radiosensitivity is a quantitative trait that is generally subject to binomial distribution. Individual radiosensitivity, however, may deviate significantly from the mean (by 2-3 standard deviations). Thus, the same dose of radiation may result in different levels of genotoxic damage (commonly measured as chromosome aberration rates) in different individuals. There is significant genetic component in individual radiosensitivity. It is related to carriership of variant alleles of various single-nucleotide polymorphisms (most of these in genes coding for proteins functioning in DNA damage identification and repair); carriership of different number of alleles producing cumulative effects; amplification of gene copies coding for proteins responsible for radioresistance, mobile genetic elements, and others. Among the other factors influencing individual radioresistance are: radioadaptive response; bystander effect; levels of endogenous substances with radioprotective and antimutagenic properties and environmental factors such as lifestyle and diet, physical activity, psychoemotional state, hormonal state, certain drugs, infections and others. These factors may have radioprotective or sensibilising effects. Apparently, there are too many factors that may significantly modulate the biological effects of ionising radiation. Thus, conventional methodologies for biodosimetry (specifically, cytogenetic methods) may produce significant errors if personal traits that may affect radioresistance are not accounted for

Individual capacity for repair of DNA damage and potential uses of stem cell lines for clinical applications:a matter of (genomic) integrity

Public and private human stem cell banking institutions are currently hosting hundreds of thousands partially characterized cell populations, including a significant number of human pluripotentstem cell lines. To be considered for use in clinical applications, stem cell preparations must undergo rigorous testing in order to ensure safety for the recipient. With development of the methodologies for in vitro derivation, ex vivo maintenance and expansion of stem cells and targeted differentiation of multipotent and pluripotent stem cells, many novel issues were added to the list of safety concerns of cell and tissue preparations. These issues are related to the potential changes that may occur in the course of in vitro propagation of stem cells and cell-derived products, how these changes may affect the quality of the preparation; and the potential effects on the recipient. Only a limited number of studies about the role of subtle variations of individual capacity for repair of genotoxic damage in maintenance in vitro of human stem cells are currently available. Nevertheless, the assessment of individual repair capacity may play a crucial role in the safety of use of human stem cells, as it constitutes a major factor in the risk of occurrence of genomic alterations that may seriously compromise the quality of the product. This article reviews the available data about the role of individual capacity for DNA damage repair in different human stem cell types and the potential adverse effects that may occur with the use of cell preparations with inferior repair capacity