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- Structure of an enzyme and its in hibitor
- Rolling Circle Amplification Technology–Technical Details
- Development and morphogenesis: potentialities from common patterns
- Human skin analysis
- PROPERTIES OF DNA
- The Molecular Biology of HIV/AIDS
- Induction therapy of autophagy and apoptosis in melanoma cells
- Cancer as a Disease of the Cell Cycle
- Tigar or how p53 controls glycolysis
- Molecular basis of interactions between integrin and plectina
- Parallel evolution of the venom of snakes and integrin
- RCAT™—Research Reagents
- The mitofusin 2 in mitochondrial energization
- Molecular link between aging and cancer
Phenylketonuria (PKU) is a disease caused by mutations in the gene for phenylalanine hydroxylase (PAH) that is inherited as an autosomal recessive and is the most common genetic disorder of amino acid metabolism. This disease has a high genetic diversity with over 500 described mutations associated with disease. The classic way to establish a correlation between genotype and phenotype in patients has been the development of genetic and clinical studies using a large number of patients homozygous or hemizygous functional. However, given the genetic heterogeneity, many patients can not be included in this analysis, the rarity of the mutations they carry, or the wearing of two different mutations nonzero. The in vitro expression of more than a hundred of these mutations indicates that the main mechanism responsible for the disease is the destabilization of the protein and defects in intracellular folding.
Spanish researchers from the Department of Biomedicine, University of Bergen (Norway) and the Centre for Genomic Regulation in Barcelona have collaborated to analyze the impact energy of 318 amino acid change mutations in the PAH protein using the algorithm FoldX and crystal structures available for truncated forms of the protein in rat and human. The tests have allowed to dissect the effect of mutations: effects on the environment of the mutated residue (parameter y0) and the effect of Van der Waals collisions with debris coming (parameter m) that may lead to reorganization of the structure protein.
The fact that a correlation is observed between the phenotypes and associated energy penalties, allowed to set values of these parameters for the different phenotypes and use in the prediction of phenotypes associated with 238 other rare mutations, through a novel method . The method can be applied to other protein-folding diseases associated with mutations of amino acid change.
Three years ago, Eduard Batlle is ICREA research professor of the Generalitat de Catalunya and the principal investigator and coordinator of the Translational Oncology Program and the Institute of Applied biomedical research in Barcelona (IRB Barcelona). It has a complete history that includes extended periods of research in leading laboratories in oncology: completed his doctoral thesis at the Municipal Institute of Medical Research (IMIM) in 1999, spent nearly two years of postdoctoral researcher in the group in Germany and Miguel Beato four more in the Netherlands Institute for Developmental Biology. Read the rest of this entry »
Three years ago, Eduard Batlle is ICREA research professor of the Generalitat de Catalunya and the principal investigator and coordinator of the Translational Oncology Program and the Institute of Applied biomedical research in Barcelona (IRB Barcelona). It has a complete history that includes extended periods of research in leading laboratories in oncology: completed his doctoral thesis at the Municipal Institute of Medical Research (IMIM) in 1999, spent nearly two years of postdoctoral researcher in the group in Germany and Miguel Beato four more in the Netherlands Institute for Developmental Biology . Read the rest of this entry »
Reactive oxygen species (ROS) are highly toxic compounds produced in different metabolic processes. Normally, cells are capable of defending against such agents by the action of enzymes that degrade. However, increased ROS levels above the acceptable physiological limits leads to oxidative stress that may alter normal cellular functions and trigger cell death. In fact, oxidative stress in nerve cells is clearly implicated in the progression of various neurodegenerative diseases like Alzheimer’s and amyotrophic lateral sclerosis. In this sense, the study of the mechanisms that control oxidative cell death is an important part of current research of these diseases. Read the rest of this entry »
Understanding how cells organize and coordinate to form the tissues and organs in living organisms (morphogenesis) is a basic question in developmental biology. The morphogenesis requires a number of cellular processes that occur in a coordinated way in small groups of cells, including proliferation, migration, differentiation, growth, and reposicionamento rearrangement of cells within the tissue. The end result of all these processes is to form a body-dimensional structure-from the initial flat structure which are the first cells of the embryo. Read the rest of this entry »
Adenocarcinomas of the lung or breast cancer, brain metastasis sources represent two very different courses of disease. In the case of breast, brain tumor occurs many years after removal from the primary tumor, suggesting that cancer cells lack certain functions scattered to grow in other organs. The analysis in patients revealed the existence of genes that are selectively involved in bone and lung metastases. Read the rest of this entry »
The exchange of DNA between bacteria and helps them to evolve and adapt quickly to changing environment, but also constitutes a serious health problem since the same mechanism for transferring genes for resistance to antibiotics. In the case of transfer of resistance by bacterial conjugation, the protein that initiates the transfer of DNA (relaxase) is key to the process. Conjugative processing of DNA, makes a cut relaxase-specific site (nic site) in plasmid DNA transfer, being covalently bound to the 5 ‘end of nic site. Based on this cut, a mechanism of rolling circle replication produces DNA chain that is transferred to the cell container, while a second transesterification reaction, also catalyzed by relaxase, recircularize plasmid .
So, knowing in detail the biochemical reaction and three-dimensional structure of the relaxase, we can find inhibitors that prevent the transfer of DNA. However, this study of the biochemistry of the reaction has been limited by the rapid equilibrium between the cutting and religation reactions that prevents detailed study of the covalent intermediate formed.
In an article published in The EMBO Journal, the group formed by researchers at the University of Cantabria and the Institute of Biomedicine and Biotechnology of Cantabria have used oligonucleotides containing a 3′-S-link fosforotiolato the cleavage site recognized by the relaxase . This change allows the court after not produce a free 3′-OH group capable of attacking the tyrosine-phosphate bond produced the rapid religation oligonucleotide cut, but a free 3′-SH, that being a weak nucleophile can not produce this reaction relegation. These oligonucleotides ‘suicide’ move for both the reaction towards covalent adducts consider allowing the intermediate steps of the reactions catalyzed by the relaxase.
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The human genome consists of three billion pairs of nucleotides. Each nucleotide contains one of four nitrogenous bases – A, C, G or T, form the alphabet by which genetic information is stored in the DNA molecule. The grounds of one chain of DNA bases mate with another chain of strictly defined rules (A is paired with T, G – s), it suffices to determine the sequence of bases in one of them.
To identify the specific grounds in some regions of the genome is required sensor capable subnanometrovoe notice the difference between A, T, G and C. The only physical method that has such a high resolution – scanning tunneling spectroscopy. However, the sequencing of the length of the billions of links are most often used, not the physical and chemical sposoby.Genom man was decoded using the technique developed in the late 1970’s. American biochemist Frederick Sanger. This procedure is preceded by cutting sequencing study of the DNA molecule into fragments, cloning them in E. coli and multiple duplication to obtain millions of copies of each fragment. As a result of the last round of duplication, conducted in special circumstances, receive a set of copies of fragments of various lengths, each of which ends with a fluorescently labeled nucleotide. Fragments are separated by length using electrophoresis, register the light signal from each of them as it passes through the detector and obtain the nucleotide sequence of the original circuit.
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Not many people get organic substances in pure form (or in the form of homogeneous mixtures) are already in antiquity. Fats and oils, no doubt, are among their number. Therefore, their names are in all languages simple native, although the chemists call them also lipids (from the Greek “liposome” – fat). To detect them was easy because they occur in all living organisms, and often in large numbers. Nature took care of animals and plants, providing them with supplies of fuel for cold and hungry days. Animals put this fuel, mainly around the internal organs and under the skin to fat deposits at the same time served as a shock-absorbing cushion shocks and heat insulator. Other animals also have not forgotten either himself or his offspring. Those who lay their eggs, or caviar, to supply embryos and larvae necessarily include a variety of lipids in the yolk. Plants that produce seeds, also supply the germ oils. Lipids are not only fuel but also the raw material for production of active molecules, and building material for body cells, and storage of vitamins – in general, it is difficult to do without them.
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Human skin is a very complicated structure, constructed from various types of chemicals. It is an integrated system with interacting with each other chemical components. Human skin in 69-73% of water.
Different layers of the skin vary considerably in its content: the share of the epidermis is about 10%, papillary layer – 71-72%. net dermis – about 61%. Normal cells activity is under constant ionic composition and pH of body fluids. In the water, readily soluble chemical compounds containing polar groups and capable of entering into the dipole-dipole interactions with water molecules or form with hydrogen bonds (-OH,-NH, C = 0): non-polar hydrocarbon molecules poorly or not soluble in it.
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