bluuebunny/crossref_metadata_2025 huggingface dataset:
Localization of proteins to the nucleus
Authors: Rine Jasper , Barnes Georjana
Published: February 2005

Nuclear proteins are synthesized in the cytoplasm and must subsequently enter the nucleus. Recent experiments indicate some similarities and some differences between protein localization to the nucleus and localization to other organelles.
Structural and functional domains of tubulin
Authors: Maccioni Ricardo B. , Serrano Luis , Avila Jesus
Published: February 2005

The molecular aspects of the microtubule system is a research area that has developed very rapidly during the past decade. Research on the assembly mechanisms and chemistry of tubulin and the molecular biology of microtubules have advanced our understanding of microtubule formation and its regulation. The emerging view of tubulin is of a macromolecule containing spatially discrete sequences that constitute functionally different domains with respect to self‐association, interactions with microtubule associated proteins (MAPs) and specific ligands. Recent studies point to the role of the carboxyl‐terminal moiety of tubulin subunits in regulating its assembly into microtubules. These investigations combined with further studies on the spatial relationships between tubulin domains should provide new insights into the detailed structural basis of microtubule assembly.
What the papers say: Keeping it in the family: How T cells make antigen receptors
Authors: Tunnacliffe Alan
Published: February 2005

The last year has unveiled extensive information on the T‐cell antigen receptor genes. For both the α‐ and β‐chains of this molecule, it is clear that an expressed gene is compiled from several coding sequences dispersed along the chromosome. During T‐cell development, recombination events occur which create a single transcription unit from these dispersed elements. Such gene organization shows that the T‐cell receptor has close evolutionary links with immunoglobulins. Both types of molecule use the same genetic mechanisms to create the diversity necessary for antigen recognition.
Antenatal diagnosis by DNA analysis: Current status, future developments… and a few unanswered questions
Authors: Jordan B. R.
Published: February 2005

Progress in recombinant DNA technology and in mapping of the human genome makes it possible to diagnose genetic defects as early as 8–10 weeks after conception for an increasing number of genetic diseases. Further developments will bring wider applicability and increased sensitivity, making widespread application of this type of diagnosis possible. Logistical and ethical problems will however arise in the course of this development.
Bacterial plasmid stability
Authors: Summers David K. , Sherratt David J.
Published: February 2005

Bacterial plasmids are ubiquitous ‘minichromosomes’ that have major importance in clinical microbiology, as agents of pathogenicity and as carriers of antibiotic resistance, and in molecular genetics, through their role as vectors in gene manipulation. Plasmids carry a wide range of dispensable, transiently useful and often bizarre functions.1 Naturally occurring plasmids, in addition to modifying the host cell phenotype, carry genes involved in the control of their own vegetative replication, plasmid copy number2 and stable inheritance. They may also carry determinants for the conjugal transfer of DNA between bacteria.3 Whereas low‐copy‐number plasmids must be partitioned by some active process during cell division, the evidence suggests that multicopy plasmids are distributed randomly between daughter cells. Two independent determinants are necessary for the stable inheritance of multicopy plasmids, and both of these appear to act by maximizing the number of independent plasmid molecules.
Homologous recombination promoted by Chi sites and RecBC enzyme of Escherichia coli
Authors: Smith Gerald R. , Stahl Franklin W.
Published: February 2005

Chi sites are examples of special sites enhancing homologous recombination in their region of the chromosome. Chi, 5′ G‐C‐T‐G‐G‐T‐G‐G3′, is a recognition site for the RecBC enzyme, which nicks DNA near Chi as it unwinds DNA. A molecular model of genetic recombination incorporating these features is reviewed.
Host cell–plasmid interactions in the expression of DNA donor activity by F+ strains of Escherichia coli K‐12
Authors: Silverman Philip M.
Published: February 2005

DNA transfer directly from cell to cell (conjugation) is common among prokaryotes, particularly Gram‐negative bacteria like Escherichia coli. The phenomenon invariably requires a set of plasmid genes in the DNA donor cell. In addition, E. coli itself makes limited and specific contributions to the donor activity of strains carrying the conjugative plasmid F. These contributions have yet to be defined biochemically, but it is already clear that the cell envelope is an importan nexus between plasmid‐ and chromosome‐encoded proteins required for the establishment and maintenance of DNA donor activity.
The linkage of actin to non‐erythroid membranes
Authors: Brown Susan S.
Published: February 2005

The question of how actin filaments are attached to membranes is of central importance to an understanding of how actin gives rise to shape and movement in cells. A number of approaches to this question have been taken, but there have been few definitive answers. Some of the limitations of these approaches are discussed, as well as possible avenues for overcoming them.
Induction of plant gene expression by light
Authors: Thompson William F. , Kaufman L. S. , Watson J. C.
Published: February 2005

Light effects on the activity of several genes have recently been exploited in studies of plant gene expression. We discuss here some examples involving nuclear genes of higher plants, with emphasis on responses mediated by the phytochrome system. Recent work has revealed considerable diversity in the responses of different genes, indicating that several different regulatory programs are probably involved. A start has been made in studies of nuclear events associated with the changes in expression. Transcriptional regulation almost certainly occurs, although many details remain to be studied and effects on mRNA processing and turnover have not been ruled out. Recent in vitro mutagenesis and gene transfer experiments with the gene for the small subunit of RuBP carboxylase indicate that sequences involved in regulating the level of expression in the light are located 5′ to the gene within about 1 kb of the start of transcription.
Plant cell culture and natural product synthesis: An academic dream or a commercial possibility?
Authors: Fowler M. W.
Published: February 2005

Work with plant cell cultures has developed rapidly in recent years, progress being manifested particularly by the development of commercial process technology for the synthesis of selected natural products. The economics of operating a plant‐cell culture process are, however, still questionable, and a great deal still needs to be done to strengthen the underlying science before the technology can be regarded as industrially commonplace. Nonetheless, the great versatility of plants as centres of chemical synthesis suggests that, with appropriate developments in cell culture technology, this area may have a significant role to play in the fine chemicals industry of the future.
The interleukin‐1 family of molecules
Authors: Allison Anthony C.
Published: February 2005

Two types of interleukin 1 (IL‐1α and IL‐1β) have been defined by purifying the molecules from activated human peripheral blood cells, followed by cloning and expressing the molecules in Escherichia coli. Both types of IL‐1 stimulate proliferation and differentiation of T‐ and B‐lymphocytes and induce cartilage proteoglycan degradation but differ in other properties. For example, demineralization and appears to be a major mediator in the pathogenesis of joint erosion in rheumatoid arthritis. Synthetic adjuvants elicit the production of IL‐1 separate from endogenous pyrogen, and this property is required for the new generation of vaccines based on antigens produced by recombinant DNA technology.
Strategies for the design and use of tumor‐reactive human monoclonal antibodies
Authors: Gaffar S. A. , Royston I. , Glassy M. C.
Published: February 2005

Human hybridomas secreting monoclonal antibodies (MoAb) reactive with tumor cell antigens were produced in our laboratory by the immortalization of UC 729‐6 with B lymphocytes isolated from regional draining lymph nodes of cancer patients. MoAbs were purified from the hybridoma supernates by standard biochemical procedures for in vivo studies and by affinity methods for in vitro experiments. Using a novel method in the preparation of slides containing adherent tumor cells, immunoreactivities of the MoAbs were evaluated by an indirect immunofluorescence assay. Based on this data, human MoAbs can, therefore, be used as research reagents.
What the papers say: A puff is born
Authors: Spierer Pierre
Published: February 2005

Puffing of polytene chromosomes is associated with intense genetic activity. Genetic determinants of puffing in Drosophila can now be dissected by transplanting genes known to puff to other chromosomal locations by transposonmediated germ line transformation. Recent studies show that induction of a heat shock puff requires only about one hundred and fifty base pairs of DNA upstream of the gene, around the start of transcription, and not the protein coding sequence itself. Moreover, the size of the ‘ectopic’ puff was found to be related to the size of the corresponding transcript. Similar work is now in progress with hormonally‐controlled puffs.
Role of mammalian circular DNA in cellular differentiation
Authors: Yamagishi Hideo
Published: February 2005

The presence of small polydisperse extrachromosomal circular (spc) DNAs composed entirely of chromosomal sequences seems to reflect the plasticity of eukaryotic genomes. The size distribution and number of spc DNAs is found to vary with development, growth state and mitotic capacity. In particular, spc DNAs are observed to be several fold smaller in established immortal cell lines than in diploid cells with a limited life span. Analysis of cloned spc DNA fragments revealed that: (1) most of the spc DNAs thus far investigated contain repetitive sequences; (2) some of the repetitive sequences are enriched in spc DNA clones relative to their representation in the chromosome; (3) various repetitive sequences of different reiteration frequency were found in spc DNA from immortal cell lines while a particular sequence of retroposon was predominant in primary lymphoid tissue cells and stem cells; (4) most of these spc DNAs appear to represent the extra copies generated by replicon‐misfiring in immortal cell lines or by retrotranscription in stem cells, and intermediates or by‐products produced by abortive rearrangement in diploid cells with a finite replicative capacity.
What's new: Immunotoxins
Authors: Blakey David C. , Thorpe Philip E.
Published: February 2005

Immunotoxins are hybrid molecules formed by coupling antibody molecules to powerful toxins of plant or bacterial origin. In experimental systems, immunotoxins have been found to kill cancer cells with great potency and specificity. This article reviews the current status of immunotoxins and some of the problems that have to be overcome before they can be used to treat human malignant disease.
The regulation of cellular differentiation in the dimorphic yeast Candida albicans
Authors: Soll David R.
Published: February 2005

Dimorphism in the yeast Candida albicans provides an unusually simple model system for investigating the mechanisms which regulate cellular differentiation, or cell divergence. Under the regime of pH‐regulated dimorphism, it has been demonstrated that the programs of protein synthesis accompanying bud and hypha formation are strikingly similar. Instead of dramatic differences in the repertoire of gene products possessed by bud‐ and hypha‐forming cells, subtle temporal, spatial and quantitative differences in the same architectural events appear to be basic to the genesis of alternative phenotypes. This emerging story of phenotypic regulation does not exclude differential gene expression, but rather de‐emphasizes its role and underscores other mechanisms which are not generally considered.
Archaebacteria: The road to the universal ancestor
Authors: Wais Allen C.
Published: February 2005

Living forms are now divided into three primary kingdoms, eubacteria, archaebacteria and eukaryotes. The archaebacteria demonstrate a blending of eubacterial and eukaryotic features and cast new perspectives on the nature of the universal ancestor.
Molecular mechanisms of the chromosome condensation and decondensation cycle in mammalian cells
Authors: Adlakha Ramesh C. , Rao Potu N.
Published: February 2005

The chromosomes undergo a condensation‐decondensation cycle within the life cycle of mammalian cells. Chromosome condensation is a complex and critical event that is necessary for the equal distribution of genetic material between the two daughter cells. Although chromosome condensation‐decondensation and segregation is mechanistically complex, it proceeds with high fidelity during the eukaryotic cell division cycle. Cell fusion studies have indicated the presence of chromosome condensation factors in mammalian cells during mitosis. If extracts from mitotic cells are injected into immature oocytes of Xenopus laevis, they induce meiotic maturation (i.e. germinal vesicle breakdown and chromosome condensation) within 2–3 hours. Recently, we showed that the maturation‐promoting activity of the mitotic cell extracts is inactivated by certain protein factors present in cells during the G1 period. The activity of the G1 factors coincides with the process of chromosome decondensation that begins at telophase and continues throughout the G1 period. These studies have revealed that the mitotic factors and the G1 factors play a pivotal role in the regulation of condensation and decondensation of chromosomes. Furthermore, our studies strongly suggest that nonhistone protein phosphorylation and dephosphorylation may mediate chromosome condensation and decondensation, respectively.
Site‐specific mutagenesis of large DNA viral genomes
Authors: Jenkins Frank J. , Roizman Bernard
Published: February 2005

Site‐specific or target‐specific mutagenesis of viral DNA genomes, using a selectable marker system is a powerful tool for the analysis of the function of specific regions of large DNA genomes. Through these techniques the construction of vectors capable of delivering vaccines for the prevention of infectious disease in humans and animals is possible.
Cell surface receptors for picornaviruses
Authors: Colonno Richard J.
Published: February 2005

Picornaviruses can be divided into at least six receptor families based on results of competition binding and receptor antibody studies. It has been proposed that a canyon present within the virion capsid harbors the viral attachment site for this group of viruses. Cell surface proteins involved in viral attachment have been identified for both rhinoviruses and coxsackie B viruses. Several monoclonal antibodies have been isolated which specifically block the binding of some picornaviruses.
DNA interactions with the nuclear matrix and spatial organization of replication and transcription
Authors: Razin S. V.
Published: February 2005

Analysis of the DNA sequence associated with the nuclear matrix has made it possible to identify several types of DNA matrix association. Permanent attachment sites are detected in both transcriptionally active and inactive nuclei. Furthermore, replication origins have been shown to be permanently attached to the nuclear matrix. In transcriptionally active nuclei, expressed genes are also associated with the nuclear matrix. Finally, a special group of attachment sites is described; these sites are believed to maintain the fixed positions of individual chromosomes in interphase nuclei.
Immune recognition of proteins: Conclusions, dilemmas and enigmas
Authors: Smith John A. , Rose George D.
Published: February 2005

The immune system distinguishes between two types of antigenic sites: one of these binds to immunoglobulins (IgGs) (i.e. antibodies), while the other binds to receptor molecules on T lymphocytes (i.e. the T‐cell receptors (TcRs)). The latter interaction occurs only when the antigen is presented in association with a self‐transplantation antigen, a so‐called MHC‐restriction element. This article discusses what is known about the structure of antigenic sites and their molecular interactions with antibodies, MHC‐restriction elements, and T‐lymphocyte receptors.
Exploring molecular mechanisms in chemically induced cancer: Complementation of mammalian DNA repair defects by a prokaryotic gene
Authors: Margison G. P. , Brennand J. , Ockey C. H. , O'Connor P. J.
Published: February 2005

Exposure of man to chemical agents can occur intentionally, as in the treatment of disease, or inadvertently because the environment contains a wide range of synthetic or naturally occurring chemicals. The alkylating agents are a diverse group of compounds (Fig. 1) and comprise a good example of such xenobiotics, since much is known about their occurrence, and their biological effects include carcinogenicity, mutagenicity, toxicity and teratogenicity.

Exposure to potentially carcinogenic alkylating agents such as nitrosamines may occur occupationally, from cigarette smoke, from certain foodstuffs and even endogenously through the ingestion of the appropriate precursor chemicals.1 At the other extreme, the cytotoxic effects of agents such as the chloroethylating nitrosamides or mustards have been exploited in the design of certain antitumour drugs.2 The effectiveness of antitumour agents and the other, mostly adverse, biological effects of alkylating agents have been ascribed to their ability to damage cellular macromolecules, in particular DNA. This review concentrates on investigations carried out over the past two years on the role of DNA damage in carcinogenesis, but we shall see how recent advances in this area of research have also led to a better understanding of the mechanisms of the cytotoxic effects of alkylating antitumour agents.
Adaptive responses to genotoxic damage: Bacterial strategies to prevent ‐mutation and cell death
Authors: Demple Bruce
Published: February 2005

Bacteria are able to induce defense and DNA repair systems that specifically counteract the toxic effects of some important natural agents. «Adaptive responses» to alkylation and oxidation damage have revealed novel strategies for escape from certain kinds of genetic damage.
Diversification and progression of malignant tumors
Authors: Nicolson Garth L. , Rosenberg Nancy L.
Published: February 2005

Tumor‐cell diversification mechanisms insure that malignant neoplasms contain diversified tumor‐cell subpopulations. Because of the instability of tumor cell phenotypes, some malignant cells will evolve with the most favorable properties for their progression to highly metastatic cells. The rates of cellular phenotypic diversification vary greatly among different tumors, and they are probably modulated, in part, by genetic and chromosome defects and by epigenetic events that may vary widely depending upon the nature of the tumor cells and their microenvironments. As tumor diversification and selection proceed, the most malignant cell subpopulations may eventually become dominant and gradually lose their microenvironmental responsiveness. Tumor‐cell diversification mechanisms may be similar or identical to normal, developmentally regulated diversification mechanisms that are used during embryonic cell diversification and differentiation.
Genetic origin of diversity of human cytoskeletal tropomyosins
Authors: MacLeod A. R.
Published: February 2005

Human fibroblasts express five tropomyosin‐like proteins, three of which have been shown to be structurally related to each other and to tropomyoins from muscle sources. These cytoskeletal tropomyosins are transcribed from three separate, non‐overlapping structural genes. However, each of these structural genes can also produce additional tropomyosin isoforms by a tissue‐specific alternative mRNA splicing mechanism.
Gene conversion, recombination nodules, and the initiation of meiotic synapsis
Authors: Carpenter Adelaide T. C.
Published: February 2005

The nature of the relationship between the two types of meiotic recombination outcomes, exchange (crossing‐over) and simple gene conversion, has been debated for years. I here propose that these two types of events are not necessarily causally related and hypothesize that the primary role of events detected as simple gene conversion is in the recognition of homology during synapsis.
The structure of hepatitis B surface antigen and its antigenic sites
Authors: Peterson Darrell L.
Published: February 2005

Hepatitis B virus infects about 200 million people worldwide yearly. The consequences of the infection range from mild, self‐limiting hepatitis with full recovery and immunity to chronic infection with liver disease of varying severity, including fulminant hepatitis and death. Alternatively, individuals may become healthy carriers of the virus and thus serve as a reservoir of infection. In addition, all chronic carriers of the virus are also at risk for development of primary hepatocellular carcinoma later in life. Efforts to combat this disease on a global scale require an inexpensive vaccine. Studies of the hepatitis B viral coat protein (HBsAg) have permitted the development of two generations of vaccine to date, and detailed structural studies of its antigenic sites may eventually allow the development of a completely synthetic (and therefore inexpensive) vaccine in the future.
The yeast Ty element: Recent advances in the study of a model retro‐element
Authors: Adams Sally E. , Kingsman Susan M. , Kingsman Alan J.
Published: February 2005

The past three years have seen a dramatic increase in our understanding of the structural organization and expression strategies of the dispersed, repetitive yeast transposon, Ty. These studies have led to a logical comparison of Ty with retroviral proviruses and other mobile, repetitive elements. Such comparisons have culminated in the hypotheses that transposition occurs via the formation of Ty‐encoded virus‐like particles and that these particles represent a basic unit of all ‘retro‐systems’.
Protein kinases: A diverse family of related proteins
Authors: Taylor Susan S.
Published: February 2005

Homologies in amino‐acid sequence indicate that all known protein kinases share a conserved catalytic core, and, thus, belong to a related family of proteins that have evolved in part from a common ancestoral origin. This family includes cellular kinases, oncogenic viral kinases and their protooncogene counterparts, and growth factor receptors. One of the simplest and certainly the best characterized of the protein kinases at the biochemical level is the kinase that is activated in response to cAMP. The properties of this cAMP‐dependent protein kinase are reviewed with particular emphasis on the features of nucleotide binding and catalytic mechanism that are likely to be shared by all protein kinases. In spite of this conserved catalytic core, these kinases vary widely in overall structure and in the mechanisms by which each is regulated, and these differences also are compared.
Polytene chromosomes: The status of the band–interband question
Authors: Hill Ronald J. , Rudkin George T.
Published: February 2005

Cracks in the one‐gene, one‐band paradigm for polytene chromosome organization are widening. At the same time evidence is accumulating suggesting that decondensed regions of the chromosomes (puffs, diffuse bands, interbands and possibly vacuoles within some bands) are generally associated with gene transcription. A model, now on the ascendancy, is based on the proposal that the band‐interband pattern is primarily a reflection of local transcriptional state, rather than the distribution of genic and non‐genic material.
Sodium cotransport systems: Cellular, molecular and regulatory aspects
Authors: Scott D. M.
Published: February 2005

The sodium cotransport systems comprise an important group of transport proteins which are involved in the transport of a variety of organic and inorganic solutes across the cellular membrane of animal cells. These systems play a central role in a wide variety of cellular and biochemical processes. We summarize here the current state of knowledge regarding the variety, structure and regulation of this important group of membrane proteins.
Pharmacogenetics of methyl conjugation and thiopurine drug toxicity
Authors: Weinshilboum Richard
Published: February 2005

Pharmacogenetics is the study of inherited variations in drug response Pharmacogenetics uses the techniques of pharmacology, population genetics, biochemical genetics and, most recently, molecular biology, to study the biological basis for individual variation in therapeutic response and in the occurrence of adverse reactions to medications. Most pharmacogenetic experiments deal with inherited differences in drug metabolism. The discussion here will review inherited variation in the activity of thiopurine methyltransferase, an enzyme that catalyzes the methyl conjugation of an important group of drugs, the thiopurines.
Composition and expression of spectrin‐based membrane skeletons in non‐erythroid cells
Authors: Moon Randall T. , McMahon Andrew P.
Published: February 2005

Cellular differentiation is often accompanied by the expression of specialized plasma membrane proteins which accumulate in discrete regions. The biogenesis of these specialized membrane domains involves the assembly and co‐localisation of a spectrin‐based membrane skeleton. While the constituents of the membrane skeleton in non‐erythroid cells are often immunologically related to erythroid spectrin, ankyrin, and protein 4.1, there are structural and functional differences between the isoforms of these membrane skeleton polypeptides, as well as highly variable patterns of expression during cellular differentiation. We consider this heterogeneity of structure and expression during development in the context of the hypothesis that non‐erythroid spectrin, ankyrin, and protein 4.1 are involved in the formation of specialized membrane domains.
Gelsolin: Calcium‐ and polyphosphoinositide‐regulated actin‐ modulating protein
Authors: Yin H. L.
Published: February 2005

Receptor‐mediated stimulation induces massive actin polymerization and cyto‐skeletal reorganization. The activity of a potent actin‐modulating protein, gelsolin, is regulated both by Ca2+ and polyphos‐phoinositides, and it may have a pivotal role in restructuring the actin cytoskeleton in response to agonist stimulation. Structure‐function analysis of gelsolin has (1) indicated that its NH2‐terminal half is primarily responsible for modulating actin filament length and polymerization; and (2) elucidated mechanisms by which Ca2+ and phospholipids may regulate such functions. Gelsolin is functionally and structurally similar to villin, another Ca2+‐activated actin‐severing protein found in microvilli, suggesting that gelsolin may be a prototype of this family of actin‐modulating proteins. A molecular variant of gelsolin is secreted and may be involved in the clearance of actin filaments released during tissue damage. The two forms of gelsolin are encoded by a single gene, and distinct messages are derived by alternative message splicing.
The phenomenological study of the assembly of muscle and non‐muscle actin; A history in Japan
Authors: Oosawa Fumio
Published: February 2005

This is a brief historical view, based on my personal experience, of the phenomenological study of the assembly of actin in Japan. The morphogenesis and dynamics of protein filaments and cytoskeleton now represent one of the central problems in cell biology. The approach to this problem at the molecular level was first undertaken on actin from muscle.
Where may reaction–diffusion mechanisms be operating in metameric patterning of Drosophila embryos?
Authors: Harrison Lionel G. , Tan Karen Y.
Published: February 2005

Two general features of metameric patterning in Drosophilaare considered: (1) maintenance of a constant number of metameres (segments or parasegments) in the face of variation in length of the embryo; (2) expression of pattern by on‐off switchings of particular genes, with only three or four rows of cells to each element of pattern. For each of these features, the general strategic question is raised: could reaction‐diffusion theory account for this? In both cases, it is answered affirmatively. For the second feature, this review contains some hitherto unpublished computer simulations by one of us (K. Y. T.), illustrating that a reaction‐diffusion mechanism can be transformed into a patterned switching mechanism by nothing more than compartmenting of the diffusion region. For the scale of three compartments to one pattern repeat unit (representing three rows of cells to a segment) the switching pattern predicted by computation is two‐off to one‐on. This resembles the pattern of expression of the engrailed gene, posteriorly localized in each segment.
Translational regulation in sea urchin eggs: A complex interaction of biochemical and physiological regulatory mechanisms
Authors: Winkler Matthew
Published: February 2005

The unfertilized sea urchin egg is a metabolically quiescent cell. Fertilization results in the activation of a variety of metabolic and biosynthetic pathways, including a 20‐ to 40‐fold increase in the rate of protein synthesis by 2 h after fertilization. This increase is regulated at a purely translational level without the need for new transcription. The greatest part of this increase is due to the translation of stored maternal mRNAs which were not translated in the egg. There is also a 2‐to 3‐fold increase in the peptide elongation rate. The molecular and physiological mechanisms responsible for this activation process are beginning to be understood, and turn out to be much more complex than was anticipated.
The pathogenesis of maturity‐onset diabetes mellitus: Is there a link to islet amyloid polypeptide?
Authors: Westermark Per , Johnson Kenneth H.
Published: February 2005

The discovery of a novel polypeptide (Islet Amyloid Polypeptide: IAPP) isolated from human and cat islet amyloid and from amyloid of a human insulinoma is reviewed. Structurally, IAPP from the human and cat resembles calcitonin gene‐related peptide (CGRP). The structural similarities between the neuropeptide CGRP and IAPP support the premise that IAPP is hormonal in nature. Our immunohistochemical studies also indicate that normal islet B‐cells of several mammalian species (including man and cat) give strong immunoreactivity with antiserum directed to a synthetic peptide segment of IAPP. The fact that IAPP is deposited as amyloid in the pancreatic islets of type 2 (noninsulin‐dependent) diabetics strongly supports an important but yet unknown link between IAPP and the development of this disease.
Human cytogenetics: Some reminiscences
Authors: Barr Murray L.
Published: February 2005

Roots present first‐hand accounts of discoveries in genetics, molecular biology, cellular biology, and developmental biology. In the following article, Murray L. Barr describes the background to and the events surrounding the discovery of the cytogenetic evidence for inactive × chromosomes in mammals. In the accompanying article, Michael W. McBurney reviews current molecular knowledge about the inactive × and proposes a hypothesis to explain the phenomenon.
The human genome sequence: What will it do for us?
Authors: Weinberg Robert A.
Published: February 2005

Science and Society presents discussions and commentaries on the broader implications of contemporary biological research. In an earlier article, Walter F. Bodmer presented the case for a major commitment on the part of the scientific community to the sequencing of the human genome (Bioessays 7, 41–45, July, 1987). In the following article, Robert A. Weinberg takes a critical look at the human genome project.
The ‘BN2’ gene, a regulator for the onset of chromosome condensation
Authors: Nishimoto Takeharu
Published: February 2005

This review deals with the condensation–decondensation cycle of chromatin. This cycle can be analysed in increasing detail because of the availability of well‐characterized temperature‐sensitive cell‐cycle mutants in which the control for condensation is aberrant at the non‐permissive temperature. DNA transfection and gene cloning techniques using one such mutant have resulted in the identification of a gene involved in the normal regulation of entry into mitosis.
Mitotic chromosome structure
Authors: Earnshaw William C.
Published: February 2005

The various models of chromatin fiber folding that have been proposed over the years are considered and evaluated. It is concluded that the radial loop / scaffold model is strongly supported by the available evidence, although the term ‘scaffold’ may be an unfortunate one. The scaffold is not a solid rod running the length of the chromatid but rather appears to be an aggregation of discrete anchoring complexes for the loops of the fiber. Despite support for this model, there is a need for more evidence to resolve the questions that remain.
An illustration of the use of isotopes: The biosynthesis of porphyrins
Authors: Shemin David
Published: February 2005

In this article, David Shemin, who is now in retirement, describes how in 1944 he ingested 66 g of 15N‐labeled glycine in order to determine the half‐life of hemoglobin and other blood proteins. The ramifications of the experiment led to the unravelling of the biosynthesis of porphyrins and the role of glycine and α‐aminolevulinic acid in heme, vitamin B12 and chlorophyll synthesis.
Homeobox genes and development of the vertebrate CNS
Authors: Wilkinson David G.
Published: February 2005

The discovery of homeobox genes in vertebrates may allow analysis of a basic problem in developmental neurobiology: how regional differences in CNS organization are specified during development. This view is based on the roles defined for homologous genes in Drosophila development, and is supported by studies of the patterns of homeobox gene expression in vertebrate embryos. Homeobox genes comprise a multigene family, members of which are expressed in different spatially restricted domains along the anterior‐posterior axis of the CNS. These observations are consistent with homeobox genes having roles in the positional specification of CNS organization, and experimental tests of this should be forthcoming shortly.
O‐glycosylation pathway for mucin‐type glycoproteins
Authors: Carraway Kermit L. , Hull Steven R.
Published: February 2005

O‐glycosylation is the post‐translational process whereby carbohydrate is added to hydroxylated amino acids of proteins. The major O‐glycosylation pathway in animal cells is involved in the synthesis of oligosaccharides linked by N‐acetylgalactosamine to serine or threonine residues in ‘mucin‐type’ proteins or their analogs. In this review, we discuss the evidence for the cellular localization of the biosynthetic steps in this pathway and propose a simplified, consensus version. We also propose variations of the simple pathway to account for its heterogeneity and variability in different cell types and differentiation states.
Mutations, epimutations, and the developmental programming of the maize Suppressor‐mutator transposable element
Authors: Fedoroff Nina , Masson Patrick , Banks Jo Ann
Published: February 2005

Information about the structure, function and regulation of the maize Suppressormutator (Spm) transposable element has emerged from the genetic and molecular characterization of both deletion mutations and an unconventional type of reversible genetic change (epimutation). The element is subject to an epigenetic mechanism that can either stably inactivate it or specify one of a variety of heritable programs of differential element expression in development. The essay explores the relationship between the Spm element's epigenetic developmental programming mechanism and the determinative events central to plant development and differentiation.
Immunogenicity: Role of dendritic cells
Authors: Steinman Ralph , Inaba Kayo
Published: February 2005

In the development of the immune response, the dendritic cell subset of leukocytes plays a key role in enhancing immunogenicity. Dendritic cells can pick up antigens in the tissues and move to lymphoid organs, through which T cells continually recirculate. It is proposed that dendritic cells at these sites express functions which have beenidentified in tissue culture models. These involve efficient binding to antigen‐specific T lymphocytes, as well as the induction of the lymphokines and growth factor receptors required for immunity. The dendritic cell system, apparently under the control of cytokines, is a sentinel designed to signal T cells that a significant antigen burden is present, and to generate the activated T lymphoblasts that interact with many other cell types to bring about an immune response.
Dna → DNA, and DNA → RNA → protein: Orchestration by a single complex operon
Authors: Lupski James R. , Nigel Godson G.
Published: February 2005

In Escherichia coli, the workhorse of molecular biology, a single operon is involved in the replication, transcription and translation of genetic information. This operon is controlled in a complex manner involving multiple cis‐acting regulatory sequences and trans‐acting regulatory proteins. It interacts with global regulatory networks by mechanisms which are presently being dissected.
Re‐expression of major histocompatibility complex (UMHC) class I molecules on malignant tumor cells and its effect on host‐tumor interaction
Authors: Hui Kam M.
Published: February 2005

The expression of products encoded by the major histocompatibility complex (MHC) on tumor cells has recently been studied extensively. It has been found that many malignant tumor cells have their MHC antigens ‘switched‐off’ but that these antigens are re‐expressed following DNA‐mediated gene transfer, with increased tumor immunogenicity as a result and the consequence that these ‘transformed’ tumor cells are rejected in vivo.: This review will discuss approaches that have been taken to induce strong tumor‐specific immunity by the manipulation of MHC expression on tumor cells.
Modulation of gene expression by auxin
Authors: Key Joe L.
Published: February 2005

Auxin, a class of plant hormones which affects a wide array of growth and developmental processes including cell elongation and cell division, alters gene expression in a very rapid, selective, and dramatic way. The relative level of some mRNAs decreases several fold, while that of other mRNAs increases many fold. These changes are mediated, at least in some cases, by very fast (within 5–10 min) modulation by auxin of transcription as measured by run‐off transcription assays using nuclei isolated from control and auxin‐treated tissues. Rapid turnover of mRNAs following auxin treatment also contributes to large changes in steady state concentration in some cases. The data are suggestive of multiple and complex mechanisms of regulation of expression of those genes which have been studied, using cloned cDNAs for direct quantitation of mRNA steady state levels and relative transcription rates. While there is no definitive evidence that auxin‐regulated gene expression mediates any of the growth responses effected by auxin, several lines of evidence are supportive of a very close relationship between these processes. The working hypothesis is that there is a causal relationship between the effects of auxin on gene expression and at least some of the physiological and growth responses to auxin.
The molecular genetics of early neurogenesis in Drosophila melanogaster
Authors: Knust Elisabeth , Campos‐Ortega José A.
Published: February 2005

The extent of neurogenesis in Drosophila is under the control of the so‐called neurogenic genes, named for their mutant phenotype of causing neural hyperplasia. Their wild‐type products appear to be responsible for a signal chain that decides the fate of ectodermal cells in the embryo. Various kinds of data, from cell transplantation experiments as well as from genetic and molecular analyses, suggest that the proteins encoded by the genes Notch and Delta may act at the membrane of the signal‐transmitting cells to provide a ligand to a still unknown receptor molecule; in contrast, the locus of Enhancer of split codes for several functions related to the transduction and further processing of the signal.
What is the role of the Cys‐his motif in retroviral nucleocapsid (NC) proteins?
Authors: Katz Richard A. , Jentoft Joyce E.
Published: February 2005

Retroviruses encode a small, basic nucleocapsid (NC) protein that is found complexed to genomic RNA within the viral particle. The NC protein appears to function not only in a histone‐like manner in packaging the RNA into the particle but also in specifically selecting the viral genomic RNA for packaging. A cysteine‐histidine (cys‐his) region, usually composed of 14 amino acids and reminiscent of the ‘zinc fingers’ of transcription factors, is the only highly conserved sequence element among the retroviral NC proteins. This review discusses the biochemical properties of NC, and its possible role(s) in retroviral replication. We also speculate on how the biochemical properties may relate to its function in RNA recognition and packaging.
Of men, molecules, and (Ir)reducibility
Authors: Welch G. Rickey
Published: February 2005

The subject of (ir)reducibility in biochemistry has resurfaced recently in the literature. Along with it comes a renewed emphasis on the organizational complexity of the living state and, more broadly, concern over the unity of the sciences.
Chromosome structure at interfaces between major chromatin types: Alpha‐ and Beta‐heterochromatin
Authors: Miklos George L. Gabor , Cotsell James N.
Published: February 2005

The chromocenter of Drosophila polytene chromosomes, which consists of two major chromatin types, has long been a troublesome region in molecular terms. The recent microcloning of part of this region, the isolation of a monoclonal antibody to a beta‐heterochromatin binding protein, and new in situ studies now shed a little more light on this chromosomal region.
Challenges: Characterisation of engineered proteins: Some critical reflections
Authors: Dittmer Kurt E. J. , Woolley Paul
Published: February 2005

This essay is an attempt to point up the gap between, on the one hand, the methods currently available to the biologist in the laboratory and, on the other, the kind of data that he or she would need in order to characterise genetically engineered proteins of topical biological interest in such a way as to make use of the techniques of protein engineering.
DNA topoisomerase dysfunction: A new goal for antitumor chemotherapy
Authors: Smith Paul J.
Published: February 2005

Topoisomerase enzymes – found in prokaryotes to human cells – control conformational changes in DNA and aid the orderly progression of DNA replication, gene transcription and the separation of daughter chromosomes at cell division. Several classes of anti‐cancer drugs are now recognised as topoisomerase poisons because of their ability to trap topoisomerase molecules on DNA as ‘cleavable complexes’. Understanding how drugs generate such complexes and why they are toxic to actively growing cancer cells is a major challenge for the development of modern approaches to chemotherapy.
Glycoconjugate expression during embryogenesis and its biological significance
Authors: Fenderson Bruce A. , Eddy E. M. , Hakomori Sen‐Itiroh
Published: February 2005

Many stage‐specific embryonic antigens (SSEAs) have been identified as glycoconjugates. These molecules may play diverse roles in the development of the embryo, including regulation of cell growth, recognition, and differentiation. The example of SSEA‐1 is described in detail. This molecule appears to play an essential role in compaction of the early mouse embryo, and may illustrate the general importance of carbohydrate‐carbohydrate interactions in controlling cell surface interactions in development.
Topogenesis of peroxisomal proteins
Authors: Osumi Takashi , Fujiki Yukio
Published: February 2005

Molecular and biochemical analysis of the biogenesis of peroxisomes has made rapid progress in recent years. Research on the mechanism of targeting of peroxisomal proteins has revealed that many, but not all, peroxisomal proteins have a conserved tripeptide motif in their carboxy‐terminal portions which is required for entry into peroxisomes; the topogenic signal mechanism thus differs in these instances from those employed in mitochondria and endoplasmic reticulum. Other factors involved in peroxisome biogenesis are also coming to light.
DNA polymerase delta: A second eukaryotic DNA replicase
Authors: Downey Kathleen M. , Tan Cheng‐Keat , So Antero G.
Published: February 2005

During the past few years significant progress has been made in our understanding of the structure and function of the proteins involved in eukaryotic DNA replication. Data from several laboratories suggest that, in contrast to prokaryotic DNA replication, two distinct DNA polymerases are required for eukaryotic DNA replication, i.e. DNA polymerase delta for the synthesis of the leading strand and DNA polymerase alpha for the lagging strand. Several accessory proteins analogous to prokaryotic replication factors have been identified and some of these are specific for pol delta whereas others affect both DNA replicases. The replicases and their accessory proteins appear to be highly conserved in eukaryotes, as homologous proteins have been found in species ranging from humans to yeast.
Structure and function of the nuclear pore complex: New perspectives
Authors: Starr Christopher M. , Hanover John A.
Published: February 2005

The double membrane of the nuclear envelope is a formidable barrier separating the nucleus and cytoplasm of eukaryotic cells. However, movement of specific macromolecules across the nuclear envelope is critical for embryonic development, cell growth and differentiation. Transfer of molecules between the nucleus and cytoplasm occurs through the aqueous channel formed by the nuclear pore complex (NPC)

Abbreviations: NPC, nuclear pore complex; GlcNac, N‐acetylglucosamine; WGA, wheat germ agglutinin

. Although small molecules may simply diffuse across the NPC, transport of large proteins and RNA requires specific transport signals and is energy dependent. A family of pore glycoproteins modified by O‐linked N‐acetylglucosamine moieties are essential for transport through the NPC. Recent evidence suggests that the regulation of nuclear transport may also involve the inteaction of RNA and nuclear proteins with specific binding proteins that recognize these transport signals. Are these nuclear pore glycoproteins and signal binding proteins the ‘gatekeepers’ that control access to the genetic material? Recent evidence obtained from a combination of biochemical and genetic approaches suggests – perhaps.