Activity of selected aromatic amino acids in biological systems

Besides the structural function in proteins, aromatic amino acids are precursors of many important biological compounds essential for normal functioning of the human organism. Many of these compounds may be used as markers for identification of specific pathological states. Comprehensive knowledge about the metabolism of aromatic amino acids and mechanisms of action of their metabolites made it possible to develop effective treatments for many disorders. However, it should not be forgotten that in some pathological conditions, these compounds could not only be involved in the pathogenesis of many disease entities but could also be used as an important tool in prediction of many diseases. This paper contains a review of published literature on aromatic amino acids in the context of physiological processes of the human body and chosen social disorders, such as cancers; psychiatric disorders: depression, anxiety states, schizophrenia, bipolar affective disorders; neurodegenerative, and cardiovascular diseases; chronic kidney insufficiency or diabetes.     

Should Bacteriophages Be Classified As Parasites Or Predators?

Bacteriophages are viruses infecting bacteria and propagating in bacterial cells. They were discovered over 100 years ago, and for decades they played crucial roles as models in genetics and molecular biology and as tools in genetic engineering and biotechnology. Now we also recognize their huge role in natural environment and their importance in human health and disease. Despite our understanding of bacteriophage mechanisms of development, these viruses are described as parasites or predators in the literature. From the biological point of view, there are fundamental differences between parasites and predators. Therefore, in this article, I asked whether bacteriophages should be classified as former or latter biological entities. Analysis of the literature and biological definitions led me to conclude that bacteriophages are parasites rather than predators and should be classified and described as such. If even more precise ecological classification is needed, bacteriophages can perhaps be included in the group of parasitoids. It might be the most appropriate formal classification of these viruses, especially if strictly virulent phages are considered, contrary to phages which lysogenize host cells and those which develop according to the permanent infection mode (or chronic cycle, like filamentous phages) revealing features of classical parasites.     

The role of proteases in transforming growth factor-beta activation

Transforming growth factor-beta (TGFbeta) plays a central role in a number of developmental and pathological processes. There are 3 isoforms of TGFbeta (1-3) and all are sequestered in the extracellular matrix as latent complexes. Activation of this complex is the key biological checkpoint controlling TGF-beta bioavailability. This process is tightly regulated in a temporal, spatial and isoform specific manner highlighting its importance. There are many different mechanisms by which TGF-beta can be activated. Both serine and metalloproteinases play an important role in TGF-beta activation, at least in vitro, and many of these proteases have been implicated in pathological conditions. The mechanism of activation is distinct between the different proteases, but is not conserved between the two groups. Both serine proteases, such as plasmin, and metalloproteases, such as MMP2, can directly cleave latent TGFbeta, whereas others, such as thrombin and MMP14, interact with integrin mediated TGFbeta activation pathways. However, further studies are still required to fully understand the relevance of all of these pathways in vivo. Currently, the best described mechanism of TGF-beta1 activation in vivo is by integrins, although this process can be modulated by proteases. The primary mechanism of TGF-beta2 and TGF-beta3 activation has yet to be defined in vivo, although it is likely that TGF-beta3 is activated in a similar manner to TGF-beta1. This review describes the mechanism of protease driven TGF-beta activation, and discusses the physiological and pathological relevance of this process.     

Protein-protein interactions: principles, techniques, and their potential role in new drug development

A vast network of genes is inter-linked through protein-protein interactions and is critical component of almost every biological process under physiological conditions. Any disruption of the biologically essential network leads to pathological conditions resulting into related diseases. Therefore, proper understanding of biological functions warrants a comprehensive knowledge of protein-protein interactions and the molecular mechanisms that govern such processes. The importance of protein-protein interaction process is highlighted by the fact that a number of powerful techniques/methods have been developed to understand how such interactions take place under various physiological and pathological conditions. Many of the key protein-protein interactions are known to participate in disease-associated signaling pathways, and represent novel targets for therapeutic intervention. Thus, controlling protein-protein interactions offers a rich dividend for the discovery of new drug targets. Availability of various tools to study and the knowledge of human genome have put us in a unique position to understand highly complex biological network, and the mechanisms involved therein. In this review article, we have summarized protein-protein interaction networks, techniques/methods of their binding/kinetic parameters, and the role of these interactions in the development of potential tools for drug designing.     

Review of russian literature on biological action of DC and low-frequency AC magnetic fields

This review considers the Russian scientific literature on the influence of weak static and of low-frequency alternating magnetic fields on biological systems. The review covers the most interesting works and the main lines of investigation during the period 1900 to the present. Shown here are the historical roots, beginning with the ideas of V. Vernadsky and A. Chizhevsky, which led in the field of Russian biology to an increasing interest in magnetic fields, based on an intimate connection between solar activity and life on the Earth, and which determined the peculiar development of Russian magnetobiology. The variety of studies on the effects of magnetic storms and extremely low-frequency, periodic variations of the geomagnetic field on human beings and animals as well as on social phenomena are described. The diverse experiments involving artificial laboratory magnetic fields acting on different biological entities under different conditions are also considered. A series of theoretical advances are reviewed that have paved the way for a step-by-step understanding of the mechanisms of magnetic field effects on biological systems. The predominantly unfavorable influence of magnetic fields on living beings is shown, but the cases of favorable influence of magnetic fields on human beings and lower animals are demonstrated as well. The majority of Russian investigations in this area of science has been unknown among the non-Russian speaking audience for many reasons, primarily because of a language barrier. Therefore, it is hoped that this review may be of interest to the international scientific community.     

Adapting protein sequences for optimized therapeutic efficacy

Therapeutic proteins alleviate disease pathology by supplementing missing or defective native proteins, sequestering superfluous proteins, or by acting through designed non-natural mechanisms. Although therapeutic proteins often have the same amino acid sequence as their native counterpart, their maturation paths from expression to the site of physiological activity are inherently different, and optimizing protein sequences for properties that 100s of millions of years of evolution did not need to address presents an opportunity to develop better biological treatments. Because therapeutic proteins are inherently non-natural entities, optimization for their desired function should be considered analogous to that of small molecule drug candidates, which are optimized through expansive combinatorial variation by the medicinal chemist. Here, we review recent successes and challenges of protein engineering for optimized therapeutic efficacy.     

Protein-Protein Interactions: Principles,Techniques, and their Potential Role in New Drug Development

Abstract

A vast network of genes is inter-linked through protein-protein interactions and is critical component of almost every biological process under physiological conditions. Any disruption of the biologically essential network leads to pathological conditions resulting into related diseases. Therefore, proper understanding of biological functions warrants a comprehensive knowledge of protein-protein interactions and the molecular mechanisms that govern such processes. The importance of protein-protein interaction process is highlighted by the fact that a number of powerful techniques/methods have been developed to understand how such interactions take place under various physiological and pathological conditions. Many of the key protein-protein interactions are known to participate in disease-associated signaling pathways, and represent novel targets for therapeutic intervention. Thus, controlling protein-protein interactions offers a rich dividend for the discovery of new drug targets. Availability of various tools to study and the knowledge of human genome have put us in a unique position to understand highly complex biological network, and the mechanisms involved therein. In this review article, we have summarized protein-protein interaction networks, techniques/methods of their binding/kinetic parameters, and the role of these interactions in the development of potential tools for drug designing.     

Adhesion molecule signalling: not always a sticky business

The signalling activity of cell adhesion molecules (CAMs) such as cadherins, immunoglobulin-like CAMs or integrins has long been considered to be a direct consequence of their adhesive properties. However, there are physiological and pathological processes that reduce or even abrogate the adhesive properties of CAMs, such as cleavage, conformational changes, mutations and shedding. In some cases these 'adhesion deficient' CAMs still retain signalling properties through their cytoplasmic domains and/or their mutated or truncated extracellular domains. The ability of CAMs to activate signal transduction cascades in the absence of cell adhesion significantly extends their range of biological activities.     

Angiogenesis--vascular endothelial growth factor and its receptors]

Angiogenesis is a crucial biological process not only in the formation of cardiovascular system and organization of tissues in embryo but also in a variety of diseases including solid tumor growth and diabetic retinopathy. Several protein factors crucial for regulation of angiogenesis have recently been identified. Among these factors, VEGF is considered to be the most important regulator for vascular endothelial cell growth and differentiation both in physiological and pathological conditions. Relationship between VEGF and other regulatory factors such as Angiopoietins should be elucidated to further understand the dynamic process of angiogenesis.     

Neuroendocrine aspects of placenta and pregnancy

Placenta plays a central role in the regulation of physiological mechanisms of pregnancy, and in particular is the organ of communication between mother and fetus. This action is also related to its ability to produce hormones, growth factors and cytokines during the progression of pregnancy, and in response to stimuli such as stress and inflammation/infection. In the last years the understanding of the physiological and pathological functions of human placenta revealed the hypersecretion of hormones in presence of gestational diseases and raised the question whether this mechanism is cause of disorders of pregnancy, or part of an adaptive response of placenta to resolve adverse conditions. However, there are evidences indicating that changes of placental hormone secretion may have clinical usefulness, since they are measurable in biological fluids, and may be used as predictive markers or prognostic tools. Of particular interest is the role of corticotropin releasing hormone, urocortins and activins in the maintaining physiological pregnancy and in the pathogenesis of diseases (preterm birth and preeclampsia).     

Alternative pathways of NF-kappaB activation: a double-edged sword in health and disease

While the classical pathway of NF-kappaB activation plays critical roles in a wide range of biological processes, the more recently described "non-canonical" NF-kappaB pathway has important but more restricted roles in both normal and pathological processes. The non-canonical NF-kappaB pathway, based on processing of the nf-kappab2 gene product p100 to generate p52, appears to be involved in B-cell maturation and lymphoid development. Deregulated activation of this pathway has been observed in a variety of malignant and autoimmune diseases, thus inhibitors that specifically target p100 processing might be predicted to have potential roles as immunomodulators and in the therapy of malignant diseases. We review current understandings of NF-kappaB activation, particularly the mechanisms of p100 processing under both physiological and pathological conditions.     

Lysophosphatidic acid is a lipid mediator with wide range of biological activities. Biosynthetic pathways and mechanism of action

Lysophosphatidic acid (LPA) is a lipid mediator required for maintaining homeostasis of numerous physiological functions and also involved in development of some pathological processes through interactions with G protein-coupled receptors. Recently many data have appeared about the role of this phospholipid in humans, but pathways of LPA biosynthesis and mechanisms of its action remain unclear. This review presents modern concepts about biosynthesis, reception, and biological activity of LPA in humans. Natural and synthetic LPA analogs are considered in the view of their possible use in pharmacology as agonists and/or antagonists of G protein-coupled receptors of LPA.     

Physiological conditions can be reflected in human urine proteome and metabolome

Biomarkers are the measurable changes associated with physiological or pathophysiological processes. Urine, unlike blood, lacks mechanisms for maintaining homeostasis: it is therefore an ideal source of biomarkers that can reflect systemic changes. Urinary proteome and metabolome have been studied for their diagnostic capabilities, ability to monitor disease and prognostic utility. In this review, the effects of common physiological conditions such as gender, age, diet, daily rhythms, exercise, hormone status, lifestyle and extreme environments on human urine are discussed. These effects should be considered when biomarker studies of diseases are conducted. More importantly, if physiological changes can be reflected in urine, we have reason to expect that urine will become widely used to detect small and early changes in pathological and/or pharmacological conditions.     

Life, self-reproduction and information: beyond the machine metaphor

The problem of representing information in automation models of self-replication is considered. It is shown that, unlike in the natural reproduction process, in a computable model the reproduced entities do not contain all the information necessary for guiding the process. Current theoretical understanding of life and its replication, based on such models, is argued to be essentially inadequate. The solution to this problem is claimed to require recognition of the theoretical fact that information in living systems is different from that subsumed under the category of "knowledge", which is representable as computer programs or triggers of state transitions. A discussion of fundamentals of a new theory of information and its relationship to replication models is given and a new direction of further developments of biological theories is envisioned.     

杆菌细胞形变的机制与功能

细菌的形态是细菌分类与鉴定的核心指标。虽然在分类上细菌的基本形态有球形、杆状、弧形和螺旋形,但在不同生理和病理条件下细菌的形态会发生改变。本文对细菌的基本形态转变和杆菌的丝状形变分子机制进行了概述,并归纳了在营养缺乏、放射污染、对抗宿主免疫系统和抗生素处理等条件下细菌产生形态改变的生物学及临床意义。