bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deregulation of protein synthesis as a mechanism of neoplastic transformation
Authors: Rosenwald Igor B. 
Published: February 2005

AbstractEarly research on the cell cycle revealed correlations between protein accumulation and cell proliferation. In this review, I describe the data showing that abnormality of cell growth and tumor development are dependent upon oncogene‐induced increases in the levels and activity of factors that determine the rate of protein synthesis. It is proposed that the establishment of a vicious circle, namely oncoproteins → increase in translation → oncoproteins, is a major biological mechanism that fuels neoplastic growth. The constitutively high rates of protein synthesis and accumulation of proteins, including those necessary for DNA replication and mitosis, would drive cells to excessive proliferation.
The organizer formation: Two molecules are better than one
Authors: Lombardo Aurora 
Published: February 2005

AbstractA recent paper by Watabe et al.(1) describes the identification, in the promoter region of the organizer‐specific gene goosecoid, of two distinct growth factor responsive elements that are required for the regulation of this gene both in vitro and in vivo. This is an important finding since it provides molecular evidence in support of the recently proposed model in which the production of dorsal type mesoderm is thought to require a synergistic interaction between a general mesoderm inducing factor and a dorsalizing competence modifier(2,6–8). Furthermore, the authors provide an elegant example of how a response element can become a useful tool to map the presence of a biologically available ligand within the embryo.
Brain POU‐er
Authors: Sharp Z. Dave , Morgan William W. 
Published: February 2005

AbstractDevelopmental coordination is vital in the temporally coordinated appearance of cell types within the precise spatial architecture of the vertebrate brain and this, combined with the rich interplay between the developing brain and its target organs, is a biological problem of monumental complexity. An example is the genesis and subsequent integration of the neuroendocrine hypothalamus and the pituitary. Two recent papers(1,2) use the developing hypothalamo‐pituitary axis in order to gather a deeper understanding of these integrative mechanisms. In addition, they show that a sub‐family of homeodomain factors, the POU‐domain proteins, play a critical role in coordinating the respective ontogenies of the hypothalamus and the pituitary.
Simple sequences and the expanding genome
Authors: Hancock John M. 
Published: February 2005

AbstractRecent analysis of the contribution of replication slippage to genome evolution shows that it has played a significant role in all species from eubacteria to humans. The overall level of repetition in genomes is related to genome size and to the degree of repetition that can be measured within individual ribosomai RNA genes, suggesting that the entire genome accepts simple sequences in a concerted manner when its size increases. Although coding sequences accept simple sequences much less readily than non‐coding sequences, they accept some repeats, particularly (CAG)n, preferentially. This may have consequences for the evolution of the genes involved in trinucleotide expansion diseases and the transcriptional networks of which they may form a part.
Genome analysis with gene expression microarrays
Authors: Schena Mark 
Published: February 2005

AbstractAdvances in biochemistry, chemistry and engineering have enabled the development of a new gene expression assay. This ‘chip‐based’ approach utilizes microscopic arrays of cDNAs printed on glass as high‐density hybridization targets. Fluorescent probe mixtures derived from total cellular messenger RNA (mRNA) hybridize to cognate elements on the array, allowing accurate measurement of the expression of the corresponding genes. Array densities of >1,000 cDNAs per cm2 enable quantitative expression monitoring of a large number of genes in a single hybridization. A two‐color fluorescence detection scheme allows rapid and simultaneous differential expression analysis of independent biological samples. Mass‐produced microarrays provide a new tool for genome expression analysis that may revolutionize genetic dissection, drug discovery and human disease diagnostics.
Electric fields at the plasma membrane level: A neglected element in the mechanisms of cell signalling
Authors: Olivotto Massimo , Arcangeli Annarosa , Carlà Marcello , Wanke Enzo 
Published: February 2005

AbstractMembrane proteins possess certain features that make them susceptible to the electric fields generated at the level of the plasma membrane. A reappraisal of cell signalling, taking into account the protein interactions with the membrane electrostatic profile, suggests that an electrical dimension is deeply involved in this fundamental aspect of cell biology. At least three types of potentials can contribute to this dimension: (1) the potential across the compact layer of water adherent to membrane surfaces; this potential is affected by classical inducers of cell differentiation, like dimethylsulfoxide and hexamethylenebisacetamide; (2) the potential across the Gouy‐Chapman double layer, which accounts for the effects of extracellular cations in the modulation of differentiation; and (3) the resting potential. This last potential and its governing ion currents can be exploited in localised mechanisms of cell signalling centred on the functional association of integrin receptors with ion channels.
DNA filter elution: A window on DNA damage in mammalian cells
Authors: Kohn Kurt W. 
Published: February 2005

AbstractThis personal account traces a series of studies that led from DNA physical chemistry to anticancer drug mechanisms. Chemical crosslinking as a basis for anticancer drug actions had been suspected since the time of the first clinical reports of the effectiveness of nitrogen mustard in 1946. After the elucidation of the DNA helix‐coil transition, several nearly concurrent findings in the early 1960s established the paradigm of DNA interstrand crosslinking. The DNA filter elution phenomenon was discovered in the early 1970s, and lent itself to the development of practical assays for DNA crosslinks and other DNA lesions in mammalian cells. The assays allowed studies of the effects of DNA damaging agents at pharmacologically or toxicologically relevant doses, and have been widely applied in studies of mutagenic and chemotherapeutic agents. During the period 1979–1986, DNA filter elution studies led to the paradigm of DNA topoisomerases as targets of anticancer drug action, and this has become one of the most active areas of anticancer drug development.
Genomic imprinting in unstable DNA diseases
Authors: Petronis Arturas 
Published: February 2005

AbstractEvidence for recombination suppression has been identified in linkage studies of several unstable DNA diseases. Also sex‐specific changes in recombination frequency have been detected at the loci of Huntington's disease and myotonic dystrophy. It can be hypothesized that meiotic recombination is regulated by genome‐wide genomic imprinting and that changes in meiotic recombination imply the presence of the genomic imprinting defect. If aberrant recombination at the locus of trinucleotide repeat expansion is verified, new theoretical and experimental opportunities will arise in studies on the role of genomic imprinting in the unstable DNA diseases.
hnRNP particles
Authors: Samarina Olga P. 
Published: February 2005

AbstractThis article describes the discovery of nuclear DNA‐like RNA (dRNA or hnRNA) and ribonucleoprotein particles in eukaryotes. Native hnRNA particles were isolated by sucrose gradient sedimentation and their structural organisation – nucleic acid (i.e. RNA) wrapped in a regular way on the surface of a series of globular protein particles – was determined. This led to the formulation of the informofer cycle hypothesis for the synthesis of hnRNA as a giant precursor molecule, its transport in informosomes within the nucleus, and subsequent splicing before export from the nucleus as free mRNA.
The neutral theory is dead. Long live the neutral theory
Authors: Kreitman Martin 
Published: February 2005

AbstractThe neutral theory of molecular evolution has been instrumental in organizing our thinking about the nature of evolutionary forces shaping variation at the DNA level. More importantly, it has provided empiricists with a strong set of testable predictions and hence, a useful null hypothesis against which to test for the presence of selection. Evidence indicates that the neutral theory cannot explain key features of protein evolution nor patterns of biased codon usage in certain species. Whereas we now have a reasonable model of selection acting on synonymous changes inDrosophila, protein evolution remains poorly understood. Despite limitations in the applicability of the neutral theory, it is likely to remain an integral part of the quest to understand molecular evolution.
The coming of age of ventralising homeobox genes in amphibian development
Authors: Lemaire Patrick 
Published: February 2005

AbstractThe emerging view of early dorso‐ventral patterning of amphibian embryos is that two opposing gradients of dorsalising and ventralising secreted factors are necessary. while several transcription factors acting upstream or downstream of the dorsalising molecules have been identified, until recently little was known about the transcriptional response to ventralising signals. Now two groups describe the identification of related homeodomain proteins, Xvent‐1 and Vox, which are able to convert dorsal cells of Xenopus embryos into more ventral ones(1,2).
The roles of heterogeneous nuclear ribonucleoproteins (hnRNP) in RNA metabolism
Authors: Weighardt Florian , Biamonti Giuseppe , Riva Silvano 
Published: February 2005

AbstractIn eukaryotic cells, messenger RNAs are formed by extensive posttranscriptional processing of primary transcripts, assembled with a large number of proteins and processing factors in ribonucleoprotein complexes. The protein moiety of these complexes mainly constitutes a class of about 20 major polypeptides called heterogeneous nuclear ribonucleoproteins or hnRNPs. The function and the mechanism of action of hnRNPs is still not fully understood, but the identification of RNA binding domains and RNA binding specificities, and the development of new functional assays, has stimulated interest in them. In contrast to previous models that hypothesised a mere structural (histone‐like) function, a more diversified and dynamic role for these proteins is now emerging. In fact, they can be viewed as a subset of the trans‐acting pre‐mRNA maturation factors. They might actively participate in post‐transcriptional events such as regulated splicing and mRNA export. Moreover, recent data suggest an involvement of some of these proteins in molecular diseases. Here we present an overview of the most relevant properties of hnRNPs and discuss some emerging ideas on theiir roles.
Craniofacial defects in AP‐2 null mutant mice
Authors: Morriss‐Kay Gillian M. 
Published: February 2005

AbstractAP‐2 is a recent significant addition to the list of transcription factors that have been demonstrated by targeted gene disruption to be essential for normal development. Two recent reports of AP‐2 null mutant mice(1,2) indicate that AP‐2 holds a key position in the network of genes and proteins controlling developmental pattern and morphogenesis, and that it is particularly important for development of the cranial region and for midline fusions.
Aging mechanisms in fruit flies
Authors: Tower John 
Published: February 2005

AbstractGenetic analysis of Drosophil has provided evidence in support of two proposed evolutionary genetic mechanisms of aging: mutation accumulation and antagonistic pleiotropy. Both mechanisms result from the lack of natural selection acting on old organisms. Analyses of large numbers of flies have revealed that mortality rates do not continue to rise with age as previously thought, but plateau at advanced ages. This phenomenon has implications both for models and for definitions of aging, and may be explained by the evolutionary theories. The physiological processes and genes most relevant to aging are being identified using Drosophila lines selected in the laboratory for postponed senescence. Oxidative stress and insufficient metabolic reserves/capacity may be particularly important factors in limiting the fruitfly lifespan. Genes which exhibit aging‐related changes in expression are now being identified. Transgenic flies are being used to analyze the mechanisms of such aging‐related gene expression, and to test the effects of specific genes on aging and aging‐related deterioration.
X‐linked agammaglobulinemia (XLA): A genetic tyrosine kinase (Btk) disease
Authors: Mattsson Pekka T. , Vihinen Mauno , Smith C. I. Edvard 
Published: February 2005

AbstractX‐linked agammaglobulinemia is a heritable immunodeficiency disease caused by a differentiation abnormality, resulting in the virtual absence of B Iymphocytes and plasma cells. The affected gene encodes a cytoplasmic protein tyrosine kinase, Bruton's agammaglobulinemia tyrosine kinase, designated Btk. Btk and the other family members, Tec, Itk and Bmx, contain five regions, four of which are common structural and functional modules that are found in other signaling proteins. Mutations affect all domains of the gene, but amino acid substitutions seem to be confined to certain regions. More than 150 unique mutations have been identified and are collected in a mutation database, BTKbase. Here we discuss the three‐dimensional structural implications of such mutations and their putative functional role. Of special interest are mutations affecting the pleckstrin homology domain, as Btk is the only disease‐associated protein so far reported to carry mutations in this particular module.
Asymmetry – where evolutionary and developmental genetics meet
Authors: Batterham Philip , Davies Andrew G. , Game Anne Y. , McKenzie John A. 
Published: February 2005

AbstractThe mechanisms responsible for the fine tuning of development, where the wildtype phenotype is reproduced with high fidelity, are not well understood. The difficulty in approaching this problem is the identification of mutant phenotypes indicative of a defect in these fine‐tuning control mechanisms. Evolutionary biologists have used asymmetry as a measure of developmental homeostasis. The rationale for this was that, since the same genome controls the development of the left and right sides of a bilaterally symmetrical organism, departures from symmetry can be used to measure genetic or environmental perturbations. This paper examines the relationship between asymmtry and resistance to organophosphorous insecticides in the Australian sheep blowfly, Lucilia cuprina. A resistance gene, Rop‐1, which encodes a carboxylesterase enzyme, also confers a significant increase in asymmetry. Continued exposure of resistant populations to insecticide has selected a dominant suppressor of the asymmetry phenotype. Genetic evidence indicates that the modifier is the L. cuprina Notch homologue.
Controlling growth of the wing: Vestigial integrates signals from the compartment boundaries
Authors: Cohen Stephen M. 
Published: February 2005

AbstractIn the past few years it has become apparent that the anterior/posterior (A/P) and dorsal/ventral (D/V) compartmant boundaries serve as the source of longrange signals that organize the A/P and D/V axes of the Drosophila wing. Recent work suggests that the vestigial gene may function as a nodal point through which the growth‐controlling activity of these two patterning systems is integrated(1).
Cdc6 and DNA replication: Limited to humble origins
Authors: Heichman Karen A. 
Published: February 2005

AbstractThe budding yeast Cdc6 protein is important for regulating DNA replication intiation. Cdc6p acts at replication origins, and cdc6‐1 mutants arrest with unreplicated DNA and show elevated minichromosome loss rates. Overexpression of the related Cdc 18 protein in fission yeast results in DNA rereplication; however, Cdc6p overexpression does not cause this result. A recent paper(1) further defines the role of Cdc6p in DNA replication. Cdc6p only promotes DNA replication between the end of mitosis and late G1, and although the Cdc6 protein is highly unstable, neither degradation nor nuclear localization is critical for limiting DNA replication to this interval.
Obesity genes and the regulation of body fat content
Authors: Weigle David S. , Kuijper Joseph L. 
Published: February 2005

AbstractPhysiological investigation has demonstrated that the central nervous system monitors body composition and adjusts energy intake and expenditure to stabilize total adipose tissue mass. Genetic variations in the signalling molecules involved in this regulatory system account for the heritable component of body fat content. The application of molecular techniques to rodent models of Mendelian obesity has resulted in the characterization of five loci at which mutations produce an abnormal accumulation of body fat. The genes at these loci include agouti, which encodes a molecule that antagonizes the binding of alpha melanocyte‐stimulating hormone to its receptor; fat, which encodes carboxypeptidase E; tubby, which encodes a putative phosphodiesterase; obese, which encodes a circulating satiety protein; and diabetes, which encodes the receptor for the obese gene product. A more detailed understanding of the functional interrelationships of these genes should lead to important new insights into the causes and potential therapies for human obesity.
Adaptive mutation: A general phenomenon or special case?
Authors: Benson Spencer 
Published: February 2005

AbstractA recent article by Galitski and Roth(1) characterizes adaptive reversion of chromosomal lac− mutations in Salmonella typhimurium LT2. Using a classical genetic approach they show that adaptive reversion, as characterized by the appearance of late revertant colonies, is an exception rather than a general phenomenon for reversion of nonsense, missense, frameshift and insertion mutations. For certain mutations, however, the number of late revertants exceeds the predicted number. These excess revertants suggest that adaptive mutability is applicable to chromosomal genes as well as to genetic changes involving F plasmids and lysogenic phages.
Signaling molecules in regenerating hydra
Authors: Galliot Brigitte 
Published: February 2005

AbstractEver since it was discovered in hydra, regeneration has remained a stimulating question for developmental biologists. Cellular approaches have revealed that, within the first few hours of apical or basal hydra regeneration, differentiation and determination of nerve cells are the primary cellular events detectable. The head and foot activators (HA, FA), neuropeptides that are released upon injury, are signaling molecules involved in these processes. In conditions where it induces cellular differentiation or determination, HA behaves as an agonist of the cyclic AMP (cAMP) pathway involving the modulation of CREB nuclear transcription factor activity. This cascade would be required for proper regeneration, regardless of whether the polarity involved is apical or basal. Modulations of the protein kinase C pathway, which have been shown to affect apical or basal positional values, might signal to bring about this polarity; however, endogenous ligands responsible for this modulation are as yet unknown.
Fish technology in chromosome and genome research
Authors: Heng Henry H. Q. , Spyropoulos Barbara , Moens Peter B. 
Published: February 2005

AbstractFluorescent in situ hybridization technology is one of the most exciting and versatile research tools to be developed in recent years. It has enabled research to progress at a phenomenal rate in diverse areas of basic research as well as in clinical medicine. Fluorescent in situ hybridization has applications in physical mapping, the study of nuclear architecture and chromatin packaging, and the investigation of fundamental principles of biology such as DNA replication, RNA processing, gene amplification, gene integration and chromatin elimination. This review highlights some of these areas and provides source material for the reader who seeks more information on a specific field.
A proposed refinement of the mitochondrial free radical theory of aging
Authors: De Grey Aubrey D. N. J. 
Published: February 2005

AbstractOver recent years, evidence has been accumulating in favour of the free radical theory of aging, first proposed by Harman. Despite this, an understanding of the mechanism by which cells might succumb to the effects of free radicals has proved elusive. This paper proposes such a mechanism, based on a previously unexplored hypothesis for the proliferation of mutant mitochondrial DNA: that mitochondria with reduced respiratory function, due to a mutation or deletion affecting the respiratory chain, suffer less frequent lysosomal degradation, because they inflict free radical damage more slowly on their own membranes. Once such a mutation occurs in a mitochondrion of a non‐dividing cell, therefore, mitochondria carrying it will rapidly populate that cell, thereby destroying the cell's respiratory capability. The accumulation of cells that have undergone this transition results in aging at the organismal level. The consistency of the hypothesis with known facts is discussed, and technically feasible tests are suggested, of both the proposed mechanism and its overall contribution to mammalian aging.
Cell cycle checkpoints: Arresting progress in mitosis
Authors: Gorbsky Gary J. 
Published: February 2005

AbstractCell cycle arrest in M phase can be induced by the failure of a single chromosome to attach properly to the mitotic spindle. The same cell cycle checkpoint mediates M phase arrest when cells are treated with drugs that either disrupt or hyperstabilize spindle microtubules. Study of yeast mutants that fail to arrest in the presence of microtubule disruptors identified a set of genes important in this checkpoint pathway. Two recent papers report the cloning of human and Xenopus homologues of one of these yeast genes, called MAD2 (for mitotic arrest deficient‐2)(1,2). Introduction of antibodies to the MAD2 protein into living mammalian cells or Xenopus egg extracts abrogates the M phase arrest induced by microtubule inhibitors. This and other recent developments suggest a model for the M phase checkpoint in which unattached kinetochores inhibit the ubiquitination of proteins whose proteolysis is necessary for chromatid separation and exit from mitosis.
Functional differentiation of white and brown adipocytes
Authors: Klaus Susanne 
Published: February 2005

AbstractAdipose tissue plays an important role in mammalian energy equilibrium not only as a lipid‐dissipating, i.e. energy‐storing, tissue (white adipose tissue), but also as an energy‐dissipating one (brown adipose tissue). Brown adipocytes have the ability of facultative heat production due to a unique mitochondrial protein, the uncoupling protein (UCP). Differentiation of white and (to a lesser extent) brown adipocytes has been studied in different cell culture systems, which has led to the identification of external inducers, second messenger pathways and transcription factors involved in adipocyte differentiation. Functional differentiation of white adipocytes implies adipose conversion, whereas in brown adipocytes it insinuates additionally the development of a thermogenic function. This review discusses recent advances in the elucidation of the pathways responsible for, and the molecular bases of, adipose conversion on the one hand and development of the thermogenic properties of brown adipocytes on the other.