The molecular chaperone concept

Molecular chaperones are a ubiquitous family of cellular proteins which mediate the correct folding of other polypeptides, and in some cases their assembly into oligomeric structures, but which are not components of those final structures. Known chaperones do not possess steric information for protein folding but inhibit unproductive folding and assembly pathways which would otherwise act as dead-end kinetic traps and produce incorrect structures. Chaperones function by binding specifically and non-covalently to interactive protein surfaces that are exposed transiently during cellular processes such as protein synthesis, protein transport across membranes, DNA synthesis, the recycling of clathrin cages, the assembly of organellar complexes from imported subunits, and stress responses. This binding is reversed under circumstances which favour correct interactions and in some cases ATP hydrolysis is involved in this reversal. Some chaperones bind specifically to a structural feature present in a wide range of unrelated proteins that is accessible only during the early stages of folding. The nature of this structural feature is unknown, but its identification is an important goal of current research. Knowledge of chaperone function may be important for the production of proteins for biotechnological purposes since in some cases chaperones may improve the yield of functional product. It is likely that chaperone diseases exist which result from the failure of certain proteins to fold correctly due to changes in chaperone structure.     

Nasopharyngeal carcinoma: molecular pathogenesis and therapeutic developments

Nasopharyngeal carcinoma (NPC) is a prevalent tumour in southern China and southeast Asia, particularly in the Cantonese population, where its incidence has remained high for decades. Recent studies have demonstrated that the aetiology of NPC is complex, involving multiple factors including genetic susceptibility, infection with the Epstein-Barr virus (EBV) and exposure to chemical carcinogens. During development of the disease, viral infection and multiple somatic genetic and epigenetic changes synergistically disrupt normal cell function, thus contributing to NPC pathogenesis. NPC is highly radiosensitive and chemosensitive, but treatment of patients with locoregionally advanced disease remains problematic. New biomarkers for NPC, including EBV DNA copy number or methylation of multiple tumour suppressor genes, which can be detected in serum and nasopharyngeal brushings, have been developed for the molecular diagnosis of this tumour. Meanwhile, new therapeutic strategies such as intensity-modulated radiation therapy and immuno- and epigenetic therapies might lead to more specific and effective treatments.     

Integrating molecular tools into freshwater ecology: developments and opportunities

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Biodegradation and bioremediation of pesticide in soil: concept,method and recent developments

Biodegradation is a natural process, where the degradation of a xenobiotic chemical or pesticide by an organism is primarily a strategy for their own survival. Most of these microbes work in natural environment but some modifications can be brought about to encourage the organisms to degrade the pesticide at a faster rate in a limited time frame. This capability of microbe is some times utilized as technology for removal of contaminant from actual site. Knowledge of physiology, biochemistry and genetics of the desired microbe may further enhance the microbial process to achieve bioremediation with precision and with limited or no scope for uncertainty and variability in microbe functioning. Gene encoding for enzyme has been identified for several pesticides, which will provide a new inputs in understanding the microbial capability to degrade a pesticide and develop a super strain to achieve the desired result of bioremediation in a short time.     

Current developments in human molecular cytogenetic techniques

In the last decade a variety of fluorescence in situ hybridization (FISH) assays have been developed. In this paper we present an overview on the currently available methods in molecular cytogenetics, highlighting their advantages and limitations, as well as their applications. Even though one has to be impressed by the total number of new techniques introduced in molecular cytogenetics, one has to be aware of the fact that it is not the brilliance of a technique that is important but the scientific question that can be addressed by it. In this review special emphasis has given in describing possible strategies for the characterization of marker and derivative chromosomes in tumor- and clinical cytogenetics.     

Other developments regarding the concept of energy in biological systems

In order to recognize the realizability of inputs with different physical natures through a component, Yoneda's Lemma is applied. The major utility of this Lemma is when the components produce only energy. From this, it is assumed that a new material input must exist which was not recognized in the original developments in biological systems representation. Moreover, simple transfers of energy, between objects, components, and among both objects and components are developed under the generic name; energetical evolution. Thus, energetical evolution appears as anew element in the abstract representation of biological systems. These new concepts are incorporated into a new abstract diagram and a newM _β category. This paper was made possible by a Fellowship from the Consejo Nacional de Investigaciones Científicas y Técnicas of the República Argentina.     

What is a phenotype? History and new developments of the concept

Even though the word “phenotype”, as well as the expression “genotype–phenotype relationship”, are a part of the everyday language of biologists, they remain abstract notions that are sometimes misunderstood or misused. In this article, I begin with a review of  the genesis of the concept of phenotype and of the meaning of the genotype-phenotype “relationship" from a historical perspective. I then illustrate how the development of new approaches for exploring the living world has enabled us to phenotype organisms at multiple levels, with traits that can either be measures or parameters of functions, leading to a virtually unlimited amount of phenotypic data. Thus, pleiotropy becomes a central issue in the study of the genotype–phenotype relationship. Finally, I provide a few examples showing that important genetic and evolutionary features clearly differ with the phenotypic level considered. The way genotypic variation propagates across the phenotypic levels to shape fitness variation is an essential research program in biology.

     

Renal tubular acidosis: developments in our understanding of the molecular basis

Renal tubular acidosis is a metabolic acidosis due to impaired acid excretion by the kidney. Hyperchloraemic acidosis with a normal anion gap and normal (or near normal) glomerular filtration rate, and in the absence of diarrhoea, defines this disorder. However, systemic acidosis is not always evident and renal tubular acidosis can present with hypokalaemia, medullary nephrocalcinosis and recurrent calcium phosphate stone disease, as well as growth retardation and rickets in children, or short stature and osteomalacia in adults. Renal dysfunction in renal tubular acidosis is not always confined to acid excretion and can be part of a more generalised renal tubule defect, as in the renal Fanconi syndrome. Isolated renal tubular acidosis is more usually acquired, due to drugs, autoimmune disease, post-obstructive uropathy or any cause of medullary nephrocalcinosis. Less commonly, it is inherited and may be associated with deafness, osteopetrosis or ocular abnormalities. The clinical classification of renal tubular acidosis has been correlated with our current physiological model of how the nephron excretes acid, and this has facilitated genetic studies that have identified mutations in several genes encoding acid and base ion transporters. In vitro functional studies of these mutant proteins in cell expression systems have helped to elucidate the molecular mechanisms underlying renal tubular acidosis, which ultimately may lead to new therapeutic options in what is still treatment only by giving an oral alkali.     

Recent developments in the molecular genetics and biology of self-incompatibility

A summary of recent work on molecular aspects of self-incompatibility in Nicotiana alata is presented. The amino acid sequences of style proteins corresponding to different S-alleles of N. alata have a high level of homology in some regions and are variable in other regions. The regions of homology include N-terminal sequences as well as most of the glycosylation sites and cysteine residues. The glycosyl substituents may consist of a number of glycoforms. The isolated style S-glycoproteins inhibit in vitro growth of pollen tubes. The S-glycoproteins tested inhibited the growth of pollen of several S-genotypes, and there was some specificity in the interaction. Heat treatment of the isolated S-glycoproteins dramatically increased their activity as inhibitors of pollen tube growth, although the specificity in the interaction was lost. The nature of the S-allele products in pollen is not yet established.     

Some new developments and challenges in non-covalent molecular imprinting technology

The technique of molecular imprinting allows the formation of specific recognition and catalytic sites in macromolecules via the use of templates. Molecularly imprinted polymers have been applied in an increasing number of applications where molecular binding events are of interest. These include the use of molecularly imprinted polymers as tailor-made separation materials, antibody and receptor binding site mimics in recognition and assay systems, enzyme mimics for catalytic applications and as recognition elements in biosensors. The stability and low cost of molecularly imprinted polymers make them advantageous for use in analysis as well as in industrial-scale production and application.     

Plasma membrane rafts engaged in T cell signalling: new developments in an old concept

The receptor for advanced glycation end products (RAGE) is a single transmembrane receptor of the immunoglobulin superfamily that is mainly expressed on immune cells, neurons, activated endothelial and vascular smooth muscle cells, bone forming cells, and a variety of cancer cells. RAGE is a multifunctional receptor that binds a broad repertoire of ligands and mediates responses to cell damage and stress conditions. It activates programs responsible for acute and chronic inflammation, and is implicated in a number of pathological diseases, including diabetic complications, stroke, atheriosclerosis, arthritis, and neurodegenerative disorders. The availability of Rage knockout mice has not only advanced our knowledge on signalling pathways within these pathophysiological conditions, but also on the functional importance of the receptor in processes of cancer. Here, we will summarize molecular mechanisms through which RAGE signalling contributes to the establishment of a pro-tumourigenic microenvironment. Moreover, we will review recent findings that provide genetic evidence for an important role of RAGE in bridging inflammation and cancer.     

Latest developments in molecular docking: 2010–2011 in review

The aim of docking is to accurately predict the structure of a ligand within the constraints of a receptor binding site and to correctly estimate the strength of binding. We discuss, in detail, methodological developments that occurred in the docking field in 2010 and 2011, with a particular focus on the more difficult, and sometimes controversial, aspects of this promising computational discipline. The main developments in docking in this period, covered in this review, are receptor flexibility, solvation, fragment docking, postprocessing, docking into homology models, and docking comparisons. Several new, or at least newly invigorated, advances occurred in areas such as nonlinear scoring functions, using machine‐learning approaches. This review is strongly focused on docking advances in the context of drug design, specifically in virtual screening and fragment‐based drug design. Where appropriate, we refer readers to exemplar case studies. Copyright © 2013 John Wiley & Sons, Ltd.     

Recent developments in the cell and molecular biology of root hairs

Recent results in root hair research show that these tip-growing cells are useful models in plant cell biology research. The review covers a range of topics, but there is particular emphasis on the use of mutants in molecular (genetic) analysis.