Origin of the First Cells on Earth: A Possible Scenario

A fundamental challenge in science is to understand the assembly of the first macromolecules necessary for cellular life and the order in which this occurred. The assembly events that led to the first minimal cell capable of growth and division are a highly debatable subject. Possibly, the formation of a primitive membrane or microsphere in a hydrophobic medium provided a suitable structure where subsequent biochemical self-replication and eventually enzyme catalysis, integrated biochemical pathways, and assembly of nucleic acids occurred. In this article, I examine a possible sequence of assembly for the first primitive cell(s) on the Earth.     

Millennial musings on molecular motors

In a universe that is dominated by increasing entropy, living organisms are a curious anomaly. The organization that distinguishes living organisms from their inanimate surroundings relies upon their ability to execute vectorial processes, such as directed movements and the assembly of macromolecules and organelle systems. Many of these phenomena are executed by molecular motors that harness chemical potential energy to perform mechanical work and unidirectional motion. This article explores how these remarkable protein machines might have evolved and what roles they could play in biological and medical research in the coming decades.     

Millennial musings on molecular motors

In a universe that is dominated by increasing entropy, living organisms are a curious anomaly. The organization that distinguishes living organisms from their inanimate surroundings relies upon their ability to execute vectorial processes, such as directed movements and the assembly of macromolecules and organelle systems. Many of these phenomena are executed by molecular motors that harness chemical potential energy to perform mechanical work and unidirectional motion. This article explores how these remarkable protein machines might have evolved and what roles they could play in biological and medical research in the coming decades.     

Millennial musings on molecular motors

In a universe that is dominated by increasing entropy, living organisms are a curious anomaly. The organization that distinguishes living organisms from their inanimate surroundings relies upon their ability to execute vectorial processes, such as directed movements and the assembly of macromolecules and organelle systems. Many of these phenomena are executed by molecular motors that harness chemical potential energy to perform mechanical work and unidirectional motion. This article explores how these remarkable protein machines might have evolved and what roles they could play in biological and medical research in the coming decades.     

Bacterial evolution and silicon

This review examines the possible role of silicon in molecular evolution. It is possible silicon participated in early molecular evolution by providing a stable mineral surface or gel structure where the assembly and replication of primitive genetic information occurred. However, as molecular evolution proceeded, silicon was not required in the evolution of C-based organisms. Silicon can be accumulated by diatoms and other living organisms such as silicoflagellates, some xanthophytes, radiolarians and actinopods and plants such as grasses, ferns, horseradish, some trees and flowers, some sponges, insects and invertebrates and bacteria and fungi. Silicon also has a role in synthesis of DNA, DNA polymerase and thymidylate kinase activity in diatoms. It is not unreasonable to examine the role of silicon in early molecular evolution as it may have been part of a micro-environment in which assembly of genetic information occurred.     

Macromolecular crowding: obvious but underappreciated

Biological macromolecules evolve and function within intracellular environments that are crowded with other macromolecules. Crowding results in surprisingly large quantitative effects on both the rates and the equilibria of interactions involving macromolecules, but such interactions are commonly studied outside the cell in uncrowded buffers. The addition of high concentrations of natural and synthetic macromolecules to such buffers enables crowding to be mimicked in vitro, and should be encouraged as a routine variable to study. The stimulation of protein aggregation by crowding might account for the existence of molecular chaperones that combat this effect. Positive results of crowding include enhancing the collapse of polypeptide chains into functional proteins, the assembly of oligomeric structures and the efficiency of action of some molecular chaperones and metabolic pathways.     

Structure and biology of cartilage and bone matrix noncollagenous macromolecules

Over recent years a number of cartilage and bone matrix molecules have been identified and characterized. These include major constituents such as collagens and proteoglycans as well as a number of less-abundant matrix proteins. In several cases these proteins have been characterized by cloning and sequence analysis of the corresponding cDNA. Some properties of the macromolecules have been studied and an understanding of their functions in the structure, assembly, and breakdown of connective tissue matrix is emerging. It appears that some of these molecules have structural roles whereas others participate in the assembly of the tissue. In this paper we attempt to give a current picture of the organization and role of the noncollagenous matrix macromolecules in cartilage and bone.     

氨基酸的置换数与生物大分子进化改变量的测度

以蛋白质分子的氨基酸置换数或核酸分子的核苷酸置换数为衡量尺度 ,说明生物大分子随时间的改变 (即分子进化速率 )保持相对恒定     

A unified theory for estimation of cardiac output, volumes of distribution and renal clearance from indicator dilution curves.

The assembly of cellular structures is considered to be a linear process that begins with the synthesis of structural molecules. At various points during assembly, additional genetic information may be required for proper assembly. Based on the location of genetic information expression during assembly, structure biogenesis can be grouped into four categories: (1) those which require only information for the synthesis of structural macromolecules; (2) those which require information for the post-translational modification of precursor structural macromolecules; (3) those which require genetic information for the actual assembly step; and (4) those which require information for post-assembly modification of the structure. Examples are given to illustrate and document each of these types of assembly reactions. Further, the usefulness of this scheme for understanding intracellular and extracellular assembly processes is discussed.     

Induction kinetics of RNA and proteins in exponentially growing organisms.

A mathematical model of the induction kinetics of RNAs and proteins in exponentially growing organisms is derived, and the cellular concentrations of the induced macromolecules at a given time after induction are related to three parameters: the fraction of the synthesis of these macromolecules in total synthesis, the half life of the inducible macromolecules, and the generation time of the organisms. The model predicts that the concentrations of the inducible macromolecules reach one half of the maximum induction level within one generation time after the onset of the induction. The model also predicts that induction curves of proteins are parabolic when their mRNAs are short-lived, but sigmoid when they are stable. Observed induction curves of beta-galactosidase in Escherichia coli cells fit in the theoretical induction curves.     

Existence of an additional structural component in the basal bodies of Escherichia coli and Vibrio alginolyticus flagellae

The structure of Escherichia coli and Vibrio alginolyticus flagella was studied using electron microscopy. An additional protein structure was shown to exist in the basal bodies of intact flagella in these organisms. It is possible that this structure involves three proteins important for the assembly of flagella, energy transduction, and a change-over in the direction of flagellar rotation.     

Alignment of Synaptic Vesicle Macromolecules with the Macromolecules in Active Zone Material that Direct Vesicle Docking

Synaptic vesicles dock at active zones on the presynaptic plasma membrane of a neuron’s axon terminals as a precondition for fusing with the membrane and releasing their neurotransmitter to mediate synaptic impulse transmission. Typically, docked vesicles are next to aggregates of plasma membrane-bound macromolecules called active zone material (AZM). Electron tomography on tissue sections from fixed and stained axon terminals of active and resting frog neuromuscular junctions has led to the conclusion that undocked vesicles are directed to and held at the docking sites by the successive formation of stable connections between vesicle membrane proteins and proteins in different classes of AZM macromolecules. Using the same nanometer scale 3D imaging technology on appropriately stained frog neuromuscular junctions, we found that ∼10% of a vesicle’s luminal volume is occupied by a radial assembly of elongate macromolecules attached by narrow projections, nubs, to the vesicle membrane at ∼25 sites. The assembly’s chiral, bilateral shape is nearly the same vesicle to vesicle, and nubs, at their sites of connection to the vesicle membrane, are linked to macromolecules that span the membrane. For docked vesicles, the orientation of the assembly’s shape relative to the AZM and the presynaptic membrane is the same vesicle to vesicle, whereas for undocked vesicles it is not. The connection sites of most nubs on the membrane of docked vesicles are paired with the connection sites of the different classes of AZM macromolecules that regulate docking, and the membrane spanning macromolecules linked to these nubs are also attached to the AZM macromolecules. We conclude that the luminal assembly of macromolecules anchors in a particular arrangement vesicle membrane macromolecules, which contain the proteins that connect the vesicles to AZM macromolecules during docking. Undocked vesicles must move in a way that aligns this arrangement with the AZM macromolecules for docking to proceed.     

Analysis of X-ray and neutron scattering from biomacromolecular solutions

New developments in small-angle X-ray and neutron scattering studies of biological macromolecules in solution are presented. Small-angle scattering is rapidly becoming a streamline tool in structural molecular biology providing unique information about overall structure and conformational changes of native individual proteins, functional complexes, flexible macromolecules and assembly processes.     

Detection of intracellular macromolecule behavior under strong magnetic fields by linearly polarized light

Strong static magnetic fields on the order of 10 T have a diamagnetic force on cell components and generate a clear alignment of a smooth muscle cell assembly, parallel to the direction of the magnetic fields within an exposure period of 3 days. This work shows the effects of diamagnetic torque forces on cell component motion. Linearly polarized light was utilized to detect the displacement of intracellular macromolecules. The polarized light passed through a mass of cells in a magnetic field, and transmission of the light increased and reached a plateau 2 h after the beginning of magnetic field exposure at 14 T. However, no distinct change was observed in transmission of the light under zero magnetic field exposure. The change in polarized light intensity through the lamellar cell assembly under magnetic fields corresponds to behavioral changes in cell components. It was speculated that intracellular macromolecules rotated and showed a displacement due to diamagnetic torque forces during 2-3 h of magnetic field exposure at 14 T.     

The Origin and Evolution of Metabolic Pathways: Why and How did Primordial Cells Construct Metabolic Routes?

The emergence and evolution of metabolic pathways represented a crucial step in molecular and cellular evolution. In fact, the exhaustion of the prebiotic supply of amino acids and other compounds that were likely present on the primordial Earth imposed an important selective pressure, favoring those primordial heterotrophic cells that became able to synthesize those molecules. Thus, the emergence of metabolic pathways allowed primitive organisms to become increasingly less dependent on exogenous sources of organic compounds. Comparative analyses of genes and genomes from organisms belonging to Archaea, Bacteria, and Eukarya reveal that, during evolution, different forces and molecular mechanisms might have driven the shaping of genomes and the emergence of new metabolic abilities. Among these gene elongations, gene and operon duplications played a crucial role since they can lead to the (immediate) appearance of new genetic material that, in turn, might undergo evolutionary divergence, giving rise to new genes coding for new metabolic abilities. Concerning the mechanisms of pathway assembly, both the analysis of completely sequenced genomes and directed evolution experiments strongly support the patchwork hypothesis, according to which metabolic pathways have been assembled through the recruitment of primitive enzymes that could react with a wide range of chemically related substrates. However, the analysis of the structure and organization of genes belonging to ancient metabolic pathways, such as histidine biosynthesis, suggests that other different hypothesis, i.e., the retrograde hypothesis, may account for the evolution of some steps within metabolic pathways.     

Endocytosis and its inhibitors in basidiomycetous fungus <Emphasis Type="Italic">Rhizoctonia solani</Emphasis>

Endocytosis is a complex process of absorption from the environment (and subsequent distribution within the cell) of soluble substances, macromolecules, microparticles, etc. by means of vesicles developed by cytoplasmic membrane. Endocytosis in animal and human cells is actively and successfully studied. Thus, classification of this process in the animals (based only on the peculiarities of primary vesicle formation) includes up to ten different endocytosis pathways. Modern knowledge about endocytosis in mycelial fungi is not so extensive; therefore, its study in this group of organisms is a topical and promising direction in fundamental and applied mycology. In the present work, we studied the effect of six different inhibitors (acting both on the assembly of actin/tubulin cytoskeleton and on the formation of different types of endocytosis) on the dynamics of endocytosis in phytopathogenic heterobasidial fungus Rhizoctonia solani. The estimation of the effect of inhibitors was conducted by means of microscopic analysis of the absorption of the fluorescent marker of endocytosis AM4-64 by mycelial cells. As a result of the conducted study, four types of the inhibitor effect on the R. solani endocytosis were detected: from the complete absence of the effect to severe suppression of different stages of fungal endocytosis. It was found that four of six inhibitors used for the suppression of endocytosis in the animals and human have a suppressive effect on endocytosis of R. solani. This indicates the conservative nature of some endocytosis mechanisms in the studied fungus and probably in mycelial fungi in general. Different hypotheses concerning principles of the effect of studied inhibitors on endocytosis activity of fungi were suggested.     

Mutations in the heme b-binding residue of SDHC inhibit assembly of respiratory chain complex II in mammalian cells

Respiratory chain complex II has been extensively studied but little is known about its assembly and the role of its heme group. Mutations in the phylogenetically conserved histidine 127 of the SDHC subunit have been shown to abrogate heme binding in yeast and bacteria without impairing complex II assembly or enzymatic activities. Here we show that in mammalian cells these mutations lead to a complete reduction of SDHC in mitochondria, a destabilisation of SDHD and SDHB, and to an abrogation of complex II enzymatic activities, suggesting that in mammalian cells complex II assembly is more complex than in lower organisms.     

Secretory and endocytic pathways converge in a dynamic endosomal system in a primitive protozoan

Leishmania are a group of primitive eukaryotic trypanosomatid protozoa that are apically polarized with a flagellum at their anterior end. Surrounding the base of the flagellum is the flagellar reservoir that constitutes the site for endocytosis and exocytosis in these organisms. In the present study, we define a novel multivesicular tubular compartment involved in the intracellular trafficking of macromolecules in Leishmania . This dynamic structure appears to subtend the flagellar reservoir and extends towards the posterior end of the cell. Functional domains of several surface-expressed proteins, such as the gp63 glycosyl phosphatidyl inositol anchor and the 3'nucleotidase/nuclease transmembrane domain were fused to green fluorescent protein. These chimeric proteins were found to traffic through the secretory pathway and, while reaching their intended destinations, also accumulated within the intracellular tubular compartment. Using various compounds that are efficient fluid-phase markers used to track endocytosis in higher eukaryotes, we showed that this tubular compartment constitutes an important station in the endocytic pathway of these cells. Based on our functional observations of its role in the trafficking of expressed proteins and endocytosed markers, this compartment appears to have properties similar to endosomes of higher eukaryotes.     

Glutathione reductase in evolution

The disulfide reducing activities of GSSG-and CoASSG-reductases were measured on partially purified extracts from a variety of prokaryotes and eukaryotes. Glutathione-reductase was found in varying amounts in all eukaryotes and prokaryotes, used in this study, with the exception of the two strict anaerobes Clostridium tartarivorum and Desulfovibrio vulgaris, and the two primitive Archaebacteria Methanosarcina barkeri and Halobacterium halobium. CoASSG-reductase was found in some eukaryotes and prokaryotes, but showed no clear pattern of distribution other than its absence whenever GSSG-reductase was not present. The absence of GSSG-reductase activity in organisms lacking GSH, confirms that glutathione metabolism is not universal and suggests that this enzyme might be useful as a marker in classifying organisms. The data suggest that glutathione-reductase occurs as a result of the change from a reducing to a oxidizing atmosphere in the primitive Earth.