bluuebunny/crossref_metadata_2025 huggingface dataset:
Oncogene homologues in yeast
Authors: Wheals A. E.
Published: February 2005

Two different yeasts have a number of genes bearing striking structural and functional homologies to mammalian oncogenes. In yeast these genes are involved in the control of proliferation and early steps in the cell cycle. Many have putative protein kinase activity and some have been shown to control the activity of the enzyme adenylate cyclase which synthesizes cyclic AMP. Mutant forms of these yeast genes have oncogenic activity in mammalian cells.
What's new: Biosensors: Current applications and future potential
Authors: Foulds Nicola C. , Lowe Christopher R.
Published: February 2005

Biological molecules such as enzymes and antibodies display a unique capacity to recognize and respond to other molecules in a way which can be exploited in the development of analytical devices. In a biosensor, the biological recognition system creates a physiochemical change proximal to a suitable transducer and thereby converts the concentration of the analyte into a quantifiable electrical signal. The design and construction of these devices requires an imaginative combination of biological, chemical, physical and engineering disciplines. Biosensors will find application in a variety of analytical fields.
Roots: Early explorations of the pathways of uridine diphosphate galactose in man and in microorganisms
Authors: Kalckar Herman M.
Published: February 2005

Thirty years ago, a number of human inborn errors in carbohydrate metabolism were explored with specific enzymatic tests on blood samples (hemolysates). Hereditary galactosemia was the first example. When the inoperative step in galactose metabolism was specified, the basis for the diet therapy used on the galactosemic infants, namely galactose‐free diet, could be shown to be securely founded.

As far as galactose metabolism is concerned, the cells of the infant are faced with two problems: (i) the conversion of dietary lactose (galactosyl glucose) to glucose and its catabolites involved in energy metabolism, and (ii) the conversion of dietary glucose or lactose to galactosyl units of glycolipids and glycoprotein cell structures.

Subsequent studies on microorganisms revealed several types of hereditary defect in galactose metabolism. One type which permits the bacteria to develop a normal carbohydrate pattern in their cell walls includes an enzyme defect, like that described in the cells of the galactosemic infant. Two other types, with the inability to synthesize UDPGlc or UDPGal from glucose, do not permit the bacteria to build the fabric of the normal bacterial cell wall. This is the subject for discussion.
Natural history of the retrovirus associated with a human leukemia
Authors: Hinuma Yorio
Published: February 2005

A human retrovirus etiologically related to a unique leukemia, adult T‐cell leukemia, has been discovered. This retrovirus is endemic in certain areas and ethnic groups, such as the Japanese in Japan and Blacks in Africa. The virus is transmitted from mother to child and husband to wife and by blood transfusion. In addition, a virus like the human retrovirus has been found in various species of monkeys in Asia and Africa. This review describes and discusses recent results on the natural history of these primate lymphotropic retroviruses.
The pineal family of aromatic amine N‐acetyltransferases
Authors: Klein David C. , Voisin Pierre , Namboodiri M. A. Aryan
Published: February 2005

The mammalian pineal gland contains two types of N‐acetyltransferases which act on aromatic amines. One type preferentially acetylates arylamines such as phenetidine and aniline, whereas the other preferentially acetylates arylalkylamines such as tryptamine and phenylethylamine. The two enzymes can be distinguished by (1) molecular size, (2) regulation, and (3) inactivation characteristics. Arylalkylamine N‐acetyltransferase is involved in the regulation of melatonin synthesis in the pineal gland. A specific function of pineal arylamine N‐acetyltransferase has not been established; it may function as a nonspecific detoxification mechanism.
What's new?: The AMBIS beta scanning system
Authors: Smith Ivor
Published: February 2005

AMBIS is a complete identification system which includes (1) a highly reproducible electrophoresis unit; (2) a beta‐scanner with the ability to rapidly locate and measure beta particle emission data from a variety of isotopes and surfaces; and (3) an IBM computer with a massive data storage capacity for the emission data plus subsequent manipulation of that data. Hence it provides a rapid facility for (1) classification of all types of micro‐organisms, (2) examination of cells of multicellular plants and animals, (3) routine determination of molecular weights of one or more proteins in a complex mixture, (4) quantification of single or mixed compounds in a band, (5) scanning and quantification of dot and other blots, immunodiffusion precipitates and probes, (6) direct counting of radioactive solutions from RIA, column fractions, etc., without the need of expensive scintillation fluids with their consequent hazards, (7) circumventing the need of much time‐consuming auto‐radiography, and (8) setting up databases plus exchange and transference of data between AMBIS systems in different locations via floppy disk, modem or other forms of rapid transmission.
Non‐radioactive nucleic acid probes for the diagnosis of virus infections
Authors: Pereira H. G.
Published: February 2005

Nucleic acid hybridization is being increasingly used in viral diagnosis. Most of the assays described so far for this purpose require the use of radioactive probes. Their replacement by Non‐radioactive assays has many advantages and makes the technique feasible in routine diagnostic work. Non‐radioactive assays have had limited use but their diagnostic value has been demonstrated for a number of virus infections. They have the main advantages of employing stable probes, of avoiding safety hazards and of being easy and rapid to perform with limited laboratory facilities. Their main disadvantage compared to radioactive assays is in having relatively low sensitivity. Improvements in probe construction, in labelling and detecting methods, in sample treatment and in hybridization conditions may well increase their usefulness.
Replication origins in yeast chromosomes
Authors: Kearsey Stephen
Published: February 2005

DNA replication initiates at many sites in eukaryotic chromosomes. It has been difficult to isolate such replication origins, but a family of sequences from the yeast genome have properties which suggest that they may serve this function. The identification of these sequences together with sophisticated methods of genetic analysis, make yeast a useful organism for the study of eukaryotic DNA replication.
Molecular basis of antigenic variation in african trypanosomes
Authors: Ashall Frank
Published: February 2005

African trypanosomes, which cause sleeping sickness in man and other mammals, are able to evade immune destruction in their hosts by altering the expression of a major cell surface molecule, the variant surface glycoprotein (VSG). The VSGs are encoded by a multigene family, and antigenic variation occurs when the trypanosome switches from expression of one VSG gene to another. This switching process involves changes in the arrangement of the trypanosome genomic DNA.
Molecular biology of complement
Authors: Colten Harvey R.
Published: February 2005

Complementary DNA clones corresponding to most of the proteins of a major amplification and effector of immune host defenses, the complement system, have been isolated and characterized. Availability of these molecular probes has substantially increased our information about and understanding of the structure of the complement proteins and regulation of complement gene expression. Information about the proteins has led to the generation of potential pharmacological agents for the selective control of inflammation. Understanding of the regulatory mechanism has provided insights into the mechanisms accounting for the response to several cytokines including interferon‐gamma, interleukin‐1 and tumor necrosis factor. Finally, complement molecular genetics has been stimulated so that the basis for several complement deficiency disorders has been elucidated.
What the papers say: The influence of immunoglobulin genes in lymphoid oncogenesis
Authors: Adams Jerry M.
Published: February 2005

Illuminating insights into lymphoid oncogenesis came with the finding that the chromosome translocations characteristic of many tumors of immunoglobulin‐producing cells represent conjunction of an immunoglobulin gene locus with the myc oncogene. The potency of this combination has been underlined by recent studies in which DNA regions mimicking certain chromosome junctions of lymphomas were shown to be highly tumorigenic when inserted into the mouse germline. Nevertheless, the mechanism by which an immunoglobulin locus activates the oncogene remains largely an enigma, particularly in those cases where the two loci remain at some distance.
Mutations affecting sodium channels in Drosophila
Authors: Ganetzky Barry
Published: February 2005

Ion channels play key roles in the generation and propagation of nerve impulses by mediating ionic fluxes across excitable membranes. Elucidation of the structure and function of these proteins is a major goal in understanding the molecular mechanisms of membrane excitability. Much work has focused on sodium channels, whose activity is of primary importance in producing nerve impulses. Despite the recent cloning and sequencing of a sodium channel structural gene, many unanswered questions remain. To address some of these question genetically, Drosophila mutants with altered sodium channels are being isolated and subjected to multidisciplinary analyses. Ultimately, these can provide novel approaches for understanding the function and regulation of sodium channels at a molecular level.
Multiple levels of gene regulations in the control of amino acid biosynthesis in Saccharomyces cerevisiae
Authors: Hinnebusch Alan G.
Published: February 2005

In the yeast Saccharomyces cerevisiae, the regulation of expression of many of the enzymes for amino acid biosynthesis involves an interlinked general control system. Molecular and genetic analyses of this system reveal an underlying set of hierarchical transcriptional controls and a novel translational regulatory mechanism for governing expression of a key activator gene.
The tubulin and histone genes of Physarum polycephalum: Models for cell cycle‐regulated gene expression
Authors: Laffler Thomas G. , Carrino John J.
Published: February 2005

Although the great majority of genes are not subject to cell‐cycle controls, those that are could play a very important role in regulation of the cell cycle itself. The tubulin and histone genes of the naturally synchronous myxomycete, Physarum polycephalum, provide an excellent paradigm for such regulation. The transcription of both is highly periodic within the Physarum cycle, and curiously, both sets of genes appear to be activated at the same time. This activation appears to function as part of a developmental program, since it serves to meet future needs for each gene's product. The significance of this activation event for cell‐cycle regulation is discussed with particular regard to the nature of the mitotic oscillator.
Lymphocyte homing receptors and the immune response in vivo
Authors: Weissman Irving L.
Published: February 2005

An important aspect of the developmental maturation of lymphocytes is their capacity to locate and enter lymphoid organs with great rapidity and specificity and to follow certain routes within these organs for the attainment of particular immunological capabilities. It is now known that this “homing response” to lymphoid organs involves specific glycoprotein receptors on the lymphocyte cell surface. The biochemistry of these receptors and their significance in normal and pathological immune responses are discussed.
Role of the nuclear envelope in the regulation of mRNA transport
Authors: McDonald A. R. , Goldfine I. D.
Published: February 2005

The export of processed RNA molecules from the nucleus is an intricately regulated process, subject to various developmental and physiological controls. The structural and biochemical properties of the nuclear envelope that are involved in this process are described here.
Regulation of enzymes in isolated plant nuclei
Authors: Datta Neeraj , Roux Stanley J.
Published: February 2005

Purified nuclei are being used as a test system to study the regulation of nuclear enzymes in plants. Regulatory agents such as light, hormones and polyamines can stimulate kinases or phosphatases that control nuclear protein phosphorylation and they can modulate the activity of as yet unidentified enzymes required for transcript synthesis and/or stabilization. This essay summarizes current findings and discusses the advantages and pitfalls of using isolated nuclei to investigate how nuclear functions are controlled.
The extracellular matrix is instructive
Authors: Caplan Arnold I.
Published: February 2005

The extracellular matrix does more than just blanket cells; it also provides informational cues which affect a variety of developmental and cellular maintenance activities. The constituents of the matrix provide the fabric for cell motility and cell shape as well as anchorage sites for bioactive factors which directly affect the cell's developmental pattern or mitotic activity. The influence of the extracellular matrix is controlled by the cell's responsiveness to these complex signals. The same matrix component, for example hyaluronic acid, can have completely different effects depending on the cell's lineage and developmental history. The functional interaction between the extracellular matrix and specific cell surface receptors provides cues which affect the control of development and the maintenance and aging events that affect specific cells and tissues.
Models for MHC‐restricted T‐cell antigen recognition
Authors: Norcross Michael A.
Published: February 2005

Current models for T‐cell recognition of foreign antigen depict the T‐cell receptor as having a single antibody‐like combining site which binds a complex of MHC and antigen. An alternative hypothesis is presented here; it is proposed that the first domains of the MHC function as inverted V‐like regions to complement the TcR V‐regions in creating antigen binding sites.
Regulation of immunoglobulin variable region gene assembly: Development of the primary antibody repertoire
Authors: Berman Jeffrey E. , Malynn Barbara A. , Blackwell T. Keith , Alt Frederick W.
Published: February 2005

The immune system can generate an almost infinite number of different antibody specificities, the sum of which is the antibody repertoire. This article considers aspects of the mechanism and control of immunoglobulin variable (V) region gene assembly with a focus on how these factors may affect generation of the antibody repertoire in normal and disease states. New model systems to study the mechanism and control of V gene assembly are described, in particular the introduction of V gene recombination substrates into Abelson murine leukemia virus‐transformed pre‐B cells. Finally, a model is presented which suggests that control of V gene assembly is mediated by regulating accessibility of substrate gene segments to recombinational machinery.
The Drosophila position‐specific antigens. Clues to their morphogenetic role
Authors: Leptin Maria , Wilcox Michael
Published: February 2005

The Drosophila position‐specific antigens are a family of cell‐surface glycoprotein complexes showing spatially restricted patterns of expression. Changes in these distributions correlate with morphogenetic events like compartment‐alization and the formation of grooves and folds during tissue organization. The complexes each contain a common component associated with different variable components. Different tissues, organs and regions of the body express complexes containing different subsets of variable components. The structure of the complexes resembles that of the family of vertebrate receptors for fibronectin, molecules which function in morphogenetic processes involving cell migration and attachment. It is possible that the position‐specific antigens have a similar role in fly development.
Autoregulation of tubulin synthesis
Authors: Caron Joan M. , Kirschner Marc W.
Published: February 2005

In many mammalian cell types, increases in the level of nonpolymerized tubulin cause an inhibition in tubulin synthesis which is accompanied by a decrease in tubulin mRNA levels. To see whether inhibition is caused by nuclear or cytoplasmic events, two groups have recently examined the ability of enucleated cells to autoregulate tubulin synthesis.1,2 These experiments have demonstrated that transcription, processing, and transport of tubulin mRNAs from the nucleus to the cytoplasm are not major sites of autoregulation. Instead, monomeric tubulin must reduce, either directly or indirectly, the translatability of its own message.
The targeting of effector molecules in the immune system
Authors: Janeway Charles A.
Published: February 2005

The immune system has evolved to detect and remove foreign or non‐self molecules from the body. To perform this task, the system has coupled together specific recognition with non‐specific effector mechanisms in at least two distinct fashions, as outlined in this review.
Control of the early activation genes of T lymphocytes
Authors: Crabtree Gerald R. , Durand David
Published: February 2005

Binding of antigen or lectin to the surface of a T lymphocyte initiates a complex sequence of events which result in both T cell proliferation and the acquisition of immunologic functions. This complex sequence of events is most likely programmed and precisely timed by a series of contingent gene activations in which one member of this series activates the next. The two most obvious examples of these stages are the set of genes activated when antigen interacts with the antigen receptor and the set of genes activated when IL‐2 interacts with its receptor. However, it is likely that several other parallel pathways of gene activation are necessary to bring about T‐cell division. An example would be the antigen‐induced activation of the c‐myc gene, which in turn is likely to be involved in regulating an additional group of genes not directly controlled by either IL‐2 or antigen. A fundamental understanding of T‐lymphocyte activation necessitates identification of the factors involved in initiating each of these contingent levels of gene activation.
Discontinuous RNA synthesis through trans‐splicing
Authors: Braun Richard
Published: February 2005

In eukaryotic cells intron sequences are usually spliced out with a high degree of precision from heterogenous nuclear RNA (hnRNA) to give functional mRNA with exons in their right order. Provided with the right substrates, cell extracts can achieve the same. With exotic substrates, on the other hand, the same extracts can cut exons from one RNA and join them to exons from another RNA, a process termed trans‐splicing. In vivo, RNA trans‐splicing could lead to faulty, but also to novel proteins and, through reverse transcription, to genomic rearrangements. So far, in living cells trans‐splicing has only been invoked to occur in trypanosomes. In these unicellular organisms most if not all mRNAs are made discontinuously, so that the mature mRNAs carry, at their 5′ end, a common 35‐nucleotide sequence, called a miniexon, encoded separately in the genome. The miniexon is most likely joined to the body of the mRNA by trans‐splicing.
Coronavirus leader‐RNA‐primed transcription: An alternative mechanism to RNA splicing
Authors: Lai Michael M. C.
Published: February 2005

Many viral and cellular mRNA species contain a leader sequence derived from a distant upstream site on the same gene by a process of RNA splicing. This process usually involves either nuclear functions or self‐splicing of RNA molecules. Coronavirus, a cytoplasmic RNA virus, unfolds yet another mechanism of joining RNA, which involves the use of a free leader RNA molecule. This molecule is synthesized and dissociates from the template RNA, and subsequently reassociates with the template RNA at down‐stream initiation sites of subgenomic mRNAs to serve as the primer for transcription. This leader‐primed transcriptional process thus generates viral mRNAs with a fused leader sequence. A similar mechanism might also operate in the mRNA transcription of African trypanosomes.
Viral sequences required for neurovirulence of poliovirus
Authors: Racaniello Vincent R.
Published: February 2005

Polioviruses of reduced neurovirulence contain point mutations in the viral RNA that are responsible for the attenuated phenotype. Two such point mutations have been identified in the genomes of the Sabin live oral vaccine strains, one in the 5′‐noncoding region of the viral RNA, and one in capsid polypeptide VP3.
Prions are novel infectious pathogens causing scrapie and creutzfeldt—Jakob disease
Authors: Prusiner Stanley B.
Published: February 2005

Scrapie and Creutzfeldt–Jakob disease (CJD) are caused by prions, which appear to be different from both viruses and viroids. Prions contain protein which is required for infectivity, but no nucleic acid has been found within them. Prion proteins are encoded by a cellular gene and not by a nucleic acid within the infectious prion particle. A cellular homologue of the prion protein has been IDentified. The role of this homologue in metabolism is unknown. Prion proteins, but not the cellular homologue, aggregate into rod‐shaped particles that are histo‐chemically and ultrastructurally IDentical to amyloid. Extracellular collections of prion proteins form amyloid plaques in scrapie‐ and CJD‐infected rodent brains as well as CJD‐infected human brains. Within the plaques, prion proteins assemble to form amyloid filaments. Elucidating the molecular differences between the prion protein and its cellular homologue may be important in understanding the chemical structure and replication of prions.
Genes specifying cytokinin biosynthesis in prokaryotes
Authors: Morris Roy O. , Powell Gary K.
Published: February 2005

Cytokinins are plant hormones which have long been associated with cell division and plastid differentiation. Recently, they have been found to play a central role also in the growth of plant tumors. Certain phytopathogenic bacteria, notably Agrobacterium tumefaciens and Pseudomonas syringae pv. savastanoi, can incite tumors on dicotyledonous plants and such tumors exhibit growth which is characteristic of the presence of excess auxin and cytokinin. Genes specifying cytokinin biosynthesis have now been isolated from both sets of bacteria. The genes encode prenyl transferase responsible for cytokinin biosynthesis which, upon expression in E. coli,cause the production of the active cytokinin, zeatin. Expression of these genes in association with the plant is responsible for at least part of the tumor phenotype, although the molecular mechanisms of infection by these bacteria are apparently quite dissimilar. There is extensive homology between the cytokinin biosynthetic genes from the two sets of bacteria.
Transgenic mice
Authors: Westphal Heiner
Published: February 2005

Transgenic mice constitute an entirely new dimension of mammalian molecular genetics. They allow us to observe genes at work in the intact organism. Virtually every sector of biomedical research is likely to be affected.
Processing and termination of RNA polymerase I transcripts
Authors: Reeder Ronald H. , Labhart Paul , McStay Brian
Published: February 2005

Electron micrographs of active ribosomal genes from many species show a similar picture in which gene regions covered with nascent transcripts alternate with apparently non‐transcribed spacers. Since the gradients of visible nascent transcripts stop near the 3′ end of the 28S sequence it has often been assumed that transcription by RNA polymerase I also terminates at that point. Recent biochemical studies have shown however, that transcription continues far beyond the 3′ end of the 28S and in some species continues across the entire spacer. In this article we review the evidence for spacer transcription in Xenopus, mouse and Drosophila and discuss possible reasons for its invisibility in the electron microscope.
The zona pellucida: A coat of many colors
Authors: Wassarman Paul M.
Published: February 2005

The zona pellucida is an extracellular coat that surrounds all mammalian eggs. It is a porous matrix of interconnected filaments that are assembled from glycoproteins synthesized and secreted by growing oocytes. The zona pellucida is responsible both for species‐specific binding of sperm to unfertilized eggs and inducing bound sperm to undergo the acrosome reaction. The latter enables sperm to penetrate the extracellular coat and fertilize the egg. The zona pellucida also aids in prevention of polyspermy following fertilization and in protection of preimplantation embryos. In mice, several of these important functions can now be ascribed to specific zona pellucida glycoproteins that have been purified and characterized. Furthermore, the enzyme responsible for hatching of embryos from the zona pellucida, just prior to implantation, has been identified and characterized.
Mutant sequences as probes of protein folding mechanisms
Authors: Matthews C. Robert , Hurle Mark R.
Published: February 2005

Mutagenesis makes it possible to examine the effect of amino acid replacements on the folding and stability of proteins. The evaluation of kinetic and equilibrium folding data using reaction coordinate diagrams allows one to determine the roles that single amino acids play in the folding mechanism.
Mitogen‐specific nonresponsive mutants and the initiation of cellular proliferation
Authors: Herschman Harvey R.
Published: February 2005

A large number of molecular, physiological, and biochemical events accompany the mitogen‐induced transition from a quiescent, nonproliferating state to a cycling state. However, it is difficult to distinguish causal steps in the commitment to cell division from correlative events. To approach this problem we have isolated mitogen‐specific nonproliferative variants of 3T3 cells, namely cell lines that are unable to mount a mitogenic response to specific mitogens.
Brain protein 4.1 subtypes: A working hypothesis
Authors: Krebs Keith E. , Zagon Ian S. , Sihag Ram , Goodman Steven R.
Published: February 2005

In a companion review1 we discussed the data supporting the conclusion that at least two subtypes of spectrin exist in mammalian brain. One form is found in the cell bodies, dendrites, and post‐synaptic terminals of neurons (brain spectrin(240/235E)) and the other subtype is located in the axons and presynaptic terminals (brain spectrin(240/235)). Our recent understanding of brain spectrin subtype localization suggests a possible explanation for a conundrum concerning brain 4.1 localization. Amelin, an immunoreactive analogue of red blood cell (rbc) cytoskeletal protein 4.1, is localized in neuronal cell bodies and dendrites when brain sections are stained with antibody against rbc protein 4.1. However, it has recently been suggested that synapsin I, a neuron‐specific phosphoprotein associated with the cytoplasmic surface of small synaptic vesicles, is related to erythrocyte 4.1. In this review we hypothesize that there are at least two forms of brain 4.1: a cell body/dendritic form (amelin) which is detected with rbc protein 4.1 antibody, and a unique form found exclusively in the presynaptic terminal (synapsin I). The binding of synapsin I to brain spectrin(240/235), and its ability to stimulate the spectrin/F‐actin interaction in a phosphorylation‐dependent manner suggests a model for the regulation of synaptic transmission mediated by the neuronal cytoskeleton.
Why do chloroplasts and mitochondria contain so many copies of their genome?
Authors: Bendich Arnold J.
Published: February 2005

The very high genome copy number in cytoplasmic organelles is a puzzling fact in cell biology. It is proposed here that high copy number reflects an increased need for organellar ribosomes that can only be satisfied by the increased ribosomal RNA gene number that results from genome multiplication.
Combinatorial control of structural genes in Drosophila: Solutions that work for the animal
Authors: Cavener Douglas R.
Published: February 2005

The regulation of glucose dehydrogenase (GLD) in Drosophila illustrates the combinatorial aspects of gene regulation in development. Furthermore, the findings serve to point up a general question about cukaryotic structural gene control: is regulation of expression always optimal?
Genetics and molecular biology of rhythms
Authors: Hall Jeffrey C. , Rosbash Michael
Published: February 2005

Mutations that disrupt biological rhythms have existed in microbial and metazoan eukaryotes for some time. They have recently begun to be studied with increasing intensity, both in terms of phenotypic effects of the relevant genetic variants, and with regard to molecular isolation and analysis of the genes defined by two of the ‘clock mutations’. These genetic loci, called period (per) in Drosophila and frequency (frq) in Neurospora, influence not only the basic characteristics of circadian rhythmicity, but also temperature compensation of such daily cycle durations, ‘re‐setting’ of the rhythms' phases, and (for the per mutants) behavioral oscillations associated with much shorter than circadian periodicities. Molecular cloning of Drosophila's per gene, accompanied crucially by the locus's identification in germ‐line transformants, has led to information on its expression ‐ temporally, spatially, and in regard to heterogeneity of mRNA types. Nucleotide‐sequencing analyses of genomic DNA (and/or cDNA) from normal and mutated per alleles have (1) led to the suggestion that this clock gene encodes a family of proteoglycans (which was further indicated by application of antibody reagents obtained by manipulation of one of the gene's exons); and (2) shown that the three types of per mutations ‐ which shorten or lengthen rhythm periodicities or appear to eliminate them ‐ are associated with interesting amino‐acid substitutions or a stop codon, respectively. Analogous molecular findings are awaited from Neurospora, whose frq gene has very recently been cloned and definitively identified, in part via transformation experiments.
Regulation of drug‐metabolizing enzymes during the perinatal period in rat and human liver
Authors: Cresteil Thierry
Published: February 2005

The importance of drug‐metabolizing enzymes in developing mammals has been recently reevaluated in view of the activities and potential inducibilities of these enzymes. The role of endogenous factors raises the question of whether there is a positive regulation of the expression of drug‐metabolizing enzymes by hormones. In humans, among the different isoenzymes of cytochrome P‐450 described in adult liver, only one is absent in 20‐week‐old fetuses. Epoxide hydrolase and glutathione S‐transferases are active while UDP‐glucuronidation develops postnatally. The consequence of this asynchronous rise of activities is briefly discussed.
Topological aspects of site‐specific DNA‐inversion
Authors: Kanaar Roland , van de Putte Pieter
Published: February 2005

Site‐specific recombination events are of fundamental importance in many biological systems. In vitro experiments using purified proteins and DNA sub‐strates are yielding insights into strand exchange mechanisms and synapsis of recombination sites. By examining results across a range of systems ‐ prokaryotic and eukaryotic ‐ two distinct classes of site‐specific recombinase enzymes can be defined.
Probing the structure and function of viral RNA genomes
Authors: Nuss Donald L. , Banerjee Amiya K.
Published: February 2005

The majority of human, animal and plant viral pathogens possess genomes composed of RNA. The strategies evolved for expression and replication of viral RNA genomes can differ significantly from those utilized for expression and replication of host‐cell genetic material. Consequently, knowledge of the molecular details of these strategies can lead to a clearer understanding of the origin, evolution and control of viral pathogens. We describe recent progress in identifying important structural and functional domains of the RNA genomes and associated replicative enzymes for two very different viruses: vesicular stomatitis virus, which possesses a single‐stranded RNA genome of negative polarity, and wound tumor virus, which contains a genome composed of 12 discrete segments of double‐stranded RNA.
Evolution of haemoglobin studied by protein engineering
Authors: Nagai Kiyoshi , Luisi Ben , Shih Daniel
Published: February 2005

Vertebrate haemoglobin (Hb), the oxygen‐carrying protein of the blood, consists of two α‐ and two β‐subunits, each containing one haem, and shows cooperative oxygen binding known as the haem–haem interaction. The amino‐acid sequences of Hbs found in different species have diverged considerably and the homology in the most distantly related ones is only 40%. How can such varied amino‐acid sequences give rise to similar three‐dimensional structures and functional properties? To what extent do amino‐acid replacements affect the structure of haemoglobin? Which mutations are responsible for the functional differences between haemoglobins from different species? Expression of α‐ and β‐globins in Escherichia coli has enabled us to introduce any mutations in the haemoglobin molecule at will. By X‐ray crystallographic and functional studies of the engineered mutants, we are trying to answer these questions.
Mesodermal determination genes: Evidence from DNA methylation studies
Authors: Harrington Maureen A. , Jones Peter A.
Published: February 2005

Mouse embryo cells, primed to differentiate with the hypomethylating agent 5‐azacytidine (5‐aza‐CR), provide an excellent model system in which cellular differentiation can be studied at the molecular level. An inherent advantage of this system is the availability of clonal populations of cells representative of the non‐differentiated precursor, those whose determinative state is that of a specific lineage, and the end stage, phenotypically mature cell. Analysis of these cultures at the cellular and molecular level will advance our understanding of requirements for and the mechanism of action of growth modulators as well as the necessity for controlled expression of certain proto‐oncogenes. At a more fundamental level, the system can be used to identify, isolate and characterize genes whose expression alters the phenotypic fate of cells.
A family of closely related ATP‐binding subunits from prokaryotic and eukaryotic cells
Authors: Higgins Christopher F. , Gallagher Maurice P. , Mimmack Michael L. , Pearce Stephen R.
Published: February 2005

A large number of cellular proteins bind ATP, frequently utilizing the free energy of ATP hydrolysis to drive specific biological reactions. Recently, a family of closely related ATP‐binding proteins has been identified, the members of which share considerable sequence identity. These proteins, from both prokaryotic and eukaryotic sources, presumably had a common evolutionary origin and include the product of the white locus of Drosophila, the P‐glycoprotein which confers multidrug resistance on mammalian tumours, and prokaryotic proteins associated with such diverse processes as membrane transport, cell division, nodulation and DNA repair. A comparison of these various proteins provides valuable insights into the function and evolution of the multicomponent systems with which they are associated.
Facts and hypotheses concerning the function of non‐granulated cells in the adenohypophysis of vertebrates
Authors: Harrisson Fernand
Published: February 2005

Electron microscopic examination of the non‐granulated cells of the adenohypophysis of several species has evidenced a unity of structure amongst vertebrates. Efforts to correlate structure and function have been made, but they have often been hampered by the scarcity or absence of direct experimental methods for the investigation of their function. Yet often the evidence in favor of a given role has been circumstantial, relying on coincidences between changes in the secretory activity of the gland and changes in the ultrastructure of the non‐granulated cells or in colloid production. At the present time, the prevailing hypothesis is that, in addition to a possible role in mechanical support within the gland, the non‐granulated cells seem to be important with respect to the secretory process of the endocrine cells and/or to the metabolism of the adenohypophysis.
On the architecture of regulatory systems: Evolutionary insights and implications
Authors: Dickinson W. J.
Published: February 2005

Interspecific comparisons reveal remarkable diversity in patterns of gene expression, even among closely related species. Combinatorial regulatory mechanisms could facilitate the evolution of this diversity. However, the high degree of interdependence characteristic of combinatorial networks would represent a major constraint on evolution and might generate many features that have no direct adaptive value.
Initiation of eukaryotic DNA replication in vitro
Authors: Stillman Bruce
Published: February 2005

Recent advances in our understanding of the mechanism and regulation of eukaryotic DNA replication have been expedited by the use of cell‐free systems capable of initiation of DNA replication. The system capable of replicating plasmid DNAs containing the SV40 origin of DNA replication in vitro is a paradigm for studies on the replication of other virus DNAs and the replication of cellular chromosomes. This review outlines some of the contemporary issues and developments related to this complex problem.
Recombination in the eukaryotic nucleus
Authors: Hastings P. J.
Published: February 2005

Mitotic recombination is a repair process which is known to repair double strand breaks and to fill double‐strand gaps by copying a homologous sequence. Meiotic recombination is a process of heteroduplex formation which sometimes generates crossovers. Evidence is presented that the later stages of meiotic recombination have some characteristics of mitotic repair recombination, leading to the conclusion that mismatch repair may be a recombinogenic repair process. The evidence suggests that the recombinational repair process generates hetero‐duplex bubbles which can move. Some bubbles become crossovers. Others cease to exist, perhaps because topoisomerase activity breaks them down.
Mosaic evolution in the Drosophila genome
Authors: Martin Christopher H. , Meyerowitz Elliot M.
Published: February 2005

Investigation of the evolution of the DNA sequences that comprise a small gene cluster in five closely related species of Drosophila shows that it evolves as a mosaic, with adjacent subregions displaying very different rates and types of evolution. It appears that local differences in the influence of selectional and mutational forces result in the formation of these distinct subregions.
Origin of the cell nucleus
Authors: Cavalier‐Smith T.
Published: February 2005

The origin of mitosis and the nuclear envelope were the pivotal processes in the evolutionary origin of the nucleus; they probably occurred in a wall‐less mutant bacterium that evolved a cytoskeleton and phagocytosis about 1500 million years ago. Principles of intracellular coevolution clarify their origin, as well as that of nucleosomes, spliceosomes, and the evolution of genome size.
Novel cell surface receptors during mammalian fertilization and development
Authors: Hathaway Helen J. , Shur Barry D.
Published: February 2005

Embryogenesis requires the precise movement and reorganization of many cell and tissue types. Presumably, cell surface receptors allow cells to interact selectively with adjacent cells and with the extracellular environment, as well as initiate differentiative events by transducing appropriate signals across the plasma membrane. One cell surface component that serves as a receptor during a variety of cellular interactions is β1,4‐galactosyltransferase. Cell surface galactosyltransferase participates in diverse cellular interactions by binding its specific glycoconjugate substrate on adjacent cell surfaces or in the extracellular matrix. Biochemical, immunological, and molecular probes are being used to better define cell surface galactosyl‐transferase functional in cellular interactions during fertilization, intercellular adhesion, cell migration, and growth control.
Human papillomaviruses in oncogenesis
Authors: Lazo Pedro A.
Published: February 2005

Papillomaviruses, long associated with benign skin tumors, have been linked more recently to human cancers, particularly to cervical carcinoma. Molecular analysis of the virus has identified the transforming gene and its regulation by both viral and cellular trans:‐acting factors. This viral regulatory mechanism is altered in carcinomas. However, lack of progress in developing an in vitro system has hampered investigation of the viral life cycle and the biology of the virus‐‐host: cell interaction.
Genetic control of vaccine‐induced immunity against a parasitic helminth, Schistosoma mansoni
Authors: Sher Alan , James Stephanie
Published: February 2005

Schistosoma mansoni is one of several species of trematode helminths responsible for schistosomiasis, a major parasitic infection of man. Genetic analysis in mice has revealed that the protective immunity induced against this parasite by an attenuated larval vaccine is strongly influenced by genes regulating the activation of macrophage effector cells. The latter finding suggests that the induction of cell‐mediated immunity may be a successful strategy for a non‐living vaccine against the human infection.
The search for morphogenes in Dictyostelium
Authors: Bloom Laird , Kay Robert R.
Published: February 2005

Classical embryological studies have led to the suggestion that cells in developing tissues may be directed to differentiate along a particular pathway by the concentrations of molecules called morphogens. Studies of the slime mould Dictyostelium discoideum, which has a simple tissue pattern consisting of only two cell types, have revealed several molecules which may act as morphogens. Cyclic AMP and ammonia promote the formation of spores, while adenosine and a novel class of compounds called DIFs promote the formation of stalk cells, the alternative cell fate. The constant proportions of the two differentiated cell types observed in this organism may result from a balance among the influences of these compounds.
Genetic polymorphism and cancer susceptibility: Evidence concerning acetyltransferases and cancer of the urinary bladder
Authors: Hein David W.
Published: February 2005

Acetyltransferase enzymes expressed in hepatic and extrahepatic tissues are products of an acetyltransferase gene locus. Acetylation capacity is regulated by simple autosomal Mendelian inheritance of two codominant alleles at this locus. Human slow acetylators are predisposed to bladder cancer from arylamine chemicals. The role of the bladder in arylamine metabolism and of bladder acetyltransferases in the etiology of bladder cancer is not fully understood, but the acetylator genotype‐dependent expression of arylamine N‐acetyltransferase and N‐hydroxyarylamine O‐acetyltransferase in bladder cytosol may contribute towards the genetic predisposition of human slow acetylators to arylamine‐induced bladder cancer.
Structural characteristics of two highly selective opioid peptides
Authors: Knapp Richard J. , Yamamura Henry I. , Kazmierski Wieslaw , Hruby Victor J.
Published: February 2005

The demonstration of opioid receptors by radioligand binding and the discovery of their endogenous peptide ligands has provided a new class of compounds that can be used for the development of novel opioids. The number of potential receptor targets for such opioids has been expanded by the identification of multiple opioid receptor types The development of highly selective opioid peptides using the principles of conformational restriction permits the analysis of the structure‐activity requirements of each receptor type, and is facilitating the elucidation of the functional properties of the different opioid receptors.
Cellular and molecular biology of alzheimer's disease
Authors: Price Donald L. , Koo Edward H. , Unterbeck Axel
Published: February 2005

Alzheimer's disease results from the degeneration of neurons. Degenerating nerve cells express atypical proteins, and amyloid is deposited. We suggest that some of these events are strongly influenced by genetic factors and age. Animal models should be useful in investigating the pathogenic mechanisms that lead to the brain abnormalities seen in this disease.
Plant viruses: A tool‐box for genetic engineering and crop protection
Authors: Michael T. , Wilson A.
Published: February 2005

Traditionally, plant viruses are viewed as harmful, undesirable pathogens. However, their genomes can provide several useful ‘designer functions’ or ‘sequence modules’ with which to tailor future gene vectors for plant or general biotechnology.

The majority (77 %) of known plant viruses have single‐stranded RNA of the messenger (protein coding) sense as their genetic material. Over the past 4 years, improved in vitro transcription systems and the construction of partial of fulllength DNA copies of several plant RNA viruses have enhanced our ability to manipulate and study their genomes, particularly in the context of their pathogenic interactions with host plants.

Recently, two forms of genetically engineered protection against plant virus infections have been reported. In both, a virus‐related ‘interfering’ molecule was stably introduced into plants via the DNA‐transfer mechanism of Agro‐bacterium tumefaciens. To date, the choice of ‘interfering’ molecule has been guided by empirical field‐observations and each is effective against only a narrow range of closely‐related viruses. As yet, we do not fully understand the molecular mechanism(s) responsible for the observed protection.

The ability to manipulate the plant–pathogen relationship is a powerful tool to increase our knowledge and improve future strategies for uncoventional cropprotection by genetic engineering techniques.
Regulation of mast cell differentiation
Authors: Kitamura Yukihiko , Fujita Jun
Published: February 2005

Mast cells are a unique class of blood cell. Unlike most blood cells, undifferentiated precursors of mast cells migrate in the bloodstream, invade tissues, proliferate there and then differentiate. Even after differentiation, some mast cells may proliferate extensively. Differentiation of mast cells is regulated by both diffusible growth factors and direct contact with fibroblasts.
Position effect variegation in Drosophila: Towards a genetics of chromatin assembly
Authors: Eissenberg Joel C.
Published: February 2005

The formation of a highly condensed chromosome structure (heterochromatin) in a region of a eukaryotic chromosome can inactivate the genes within that region. Genetic studies using the fruitfly Drosophila melanogaster have identified several essential genes which influence the formation of heterochromatin. My purpose in this review is to summarize some recent work on the genetics of heterochromatin assembly in Drosophila and a recent model for how chromosomal proteins may interact to form a heterochromatic structure.
RNA folding: Pseudoknots, loops and bulges
Authors: Wyatt Jacqueline R. , Puglisi Joseph D. , Tinoco Ignacio
Published: February 2005

The three‐dimensional structures adopted by RNA molecules are crucial to their biological functions. The nucleotides of an RNA molecule interact to form characteristic secondary‐structure mctifs. Tertiary interactions orient these secondary‐structure elements with respect to each other to form the functional RNA. Here we describe the basic structural elements with special emphasis on a novel tertiary motif, the pseudoknot.