bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maize mutants and variants altering developmental time and their heterochronic interactions
Authors: Freeling Michael , Bertrand‐Garcia Ralph , Sinha Neelima 
Published: February 2005

AbstractIt is useful to envision two fundamentally different ways by which the timing of plant development is regulated: developmental stage‐transition mechanisms and time‐to‐flowering mechanisms. The existence of both mechanisms is indicated by the behavior of various mutants. Shoot stage transitions are defined by dominant mutants representing at least four different genes; each mutant retards transitions from juvenile shoot stages to more adult shoot stages. In addition, dominant leaf stage‐transition mutants in at least seven different genes have similar phenotypes, but the leaf rather than the shoot is the. focus (and at least two of these genes encode domain proteins.) One mutant, Hairy sheath frayed 1‐0 (Hsf1‐O) simultaneously affects shoot and leaf; this mutant's behavior initiated our interest in plant heterochronism(1). The second type of timekeeping involves time‐to‐flowering. As with most plant but not animals species, cultivars of the maize species vary greatly for the time‐to‐flowering quantitative trait: between 6 and 14 weeks is common. It is via the 'slipping time frames' interaction that takes place between stage‐transition mutants and time‐to‐flowering genetic back‐grounds that unexpected and radical phenotypes occur. We see a reservoir of previously unsuspected morphological possibilities among the few heterochronic genotypes we have constructed, possibilities that may mimic the sort of variation needed to fuel macroevolution without having to posit (as done by Goldschmidt(2)) any special macromutational mechanisms.
DNA precursor asymmetries, replication fidelity, and variable genome evolution
Authors: Mathews Christopher K. , Ji Jiuping 
Published: February 2005

AbstractBalanced pools of deoxyribonucleoside triphosphates (dNTPs) are essential for DNA replication to occur with maximum fidelity. Conditions that create biased dNTP pools stimulate mutagenesis, as well as other phenomena, such as recombination or cell death. In this essay we consider the effective dNTP concentrations at replication sites under normal conditions, and we ask how maintenance of these levels contributes toward the natural fidelity of DNA replication. We focus upon two questions. (1) In prokaryotic systems, evidence suggests that replication is driven by small, localized, rapidly replenished dNTP pools that do not equilibrate with the bulk dNTP pools in the cell. Since these pools cannot be analyzed directly, what indirect approaches can illuminate the nature of these replication‐active pools? (2) In eukaryotic cells, the normal dNTP pools are highly asymmetric, with dGTP being the least abundant nucleotide. Moreover, the composition of the dNTP pools changes as cells progress through the cell cycle. To what extent might these natural asymmetries contribute toward a recently described phenomenon, the differential rate of evolution of different genes in the same genome?
From cell fates to morphology: Developmental genetics of the Caenorhabditis elegans male tail
Authors: Emmons Scott W. 
Published: February 2005

AbstractThe C. elegans male tail is being studied as a model to understand how genes specify the form of multicellular animals. Morphogenesis of the specialized male copulatory organ takes place in the last larval stages during male development. Genetic analysis is facilitated because the structure is not necessary for male viability or for strain propagation. Analysis of developmental mutants, isolated in several functional and morphological screens, has begun to reveal how fates of cells are determined in the cell lineages, and how the specification of cell fates affects the morphology of the structure. Cytological studies in wild type and in mutants have been used to study the mechanism of pattern formation in the tail peripheral nervous system. The ultimate goal is to define the entire pathway leading to the male copulatory organ.
The molecular biology of desmosomes and hemidesmosomes: ′What's in a name?'
Authors: Legan P. K. , Collins J. E. , Garrod D. R. 
Published: February 2005

AbstractDesmosomes are junctions involved in intercellular adhesion of epithelial cells and hemidesmosomes are junctions involved in adhesion of epithelia to basement membranes. Both are characterised at the ultrastructural level by dense cytoplasmic plaques which are linked to the intermediate filament cytoskeleton of the cells. The plaques strongly resemble each other suggesting a relationship between the two kinds of junctions, as implied by their names. Recent characterisation of the molecular components of the junctions shows they are, in fact, quite unrelated implying that structural similarity is fortuitous. The molecular biology raises many fascinating problems relating to their structure and function.
How the EcoRI endonuclease recognizes and cleaves DNA
Authors: Heitman Joseph 
Published: February 2005

AbstractOne popular recombinant DNA tool is the EcoRI endonuclease, which cleaves DNA at GAATTC sites and serves as a paradigm for sequence specific DNA‐enzyme interactions. The recently revised X‐ray crystal structure of an EcoRI‐DNA complex reveals EcoRI employs novel DNA recognition motifs, a four α‐helix bundle and two extended chains, which project into the major groove to contact substrate purines and pyrimidines. Interestingly, pyrimidine contacts had been predicted based on genetic and biochemical studies. Current work focuses on the EcoRI active site structure, enzyme and substrate conformational changes during catalysis, and host‐restriction system interactions.
Cloning of the genes for excitatory amino acid receptors
Authors: Henneberry Richard C. 
Published: February 2005

AbstractGlutamate is the major excitatory neurotransmitter in the mammalian brain, with receptors on every neuron in the central nervous system; it has major roles in fast synaptic transmission and in the establishment of certain forms of memory. More than 20 years ago Olney and his colleagues(1) described the [Excitotoxic Hypothesis] which postulates that, in addition to its normal function in the healthy brain, glutamate can kill neurons by prolonged, receptorsmediated depolarization resulting in irreversible disturbances in ion homeostasis. Therefore, glutamate is a two‐edged sword; in certain undefined, adverse conditions it undergoes a transition from neurotransmitter to neurotoxin. Its toxicity has been implicated in the death of neurons in ischemia, epilepsy, and the neurodegenerative disorders such as Alzheimer's, Huntington's, and Parkinson's diseases(2–5). Recent advances in the molecular cloning of the genes for the glutamate family of receptors has revealed a plethora of receptor subtypes and an unexpected level of complexity in the mechanisms of receptor expression and function.
Problems and paradigms: Oscillations and waves of cytosolic calcium: Insights from theoretical models
Authors: Dupont Geneviève , Goldbeter Albert 
Published: February 2005

AbstractOscillations in cytosolic Ca2+ occur in a wide variety of cells, either spontaneously or as a result of external stimulation. This process is often accompanied by intracellular Ca2+ waves. A number of theoretical models have been proposed to account for the periodic generation and spatial propagation of Ca2+ signals. These models are reviewed and their predictions compared with experimental observations. Models for Ca2+ oscillations can be distinguished according to whether or not they rely on the concomitant, periodic variation in inositol 1,4,5‐trisphosphate. Such a variation, however, is not required in models based on Ca2+‐induced Ca2+ release. When Ca2+diffusion is incorporated into these models, propagating waves of cytosolic Ca2+ arise, with profiles and rates comparable to those seen in the experiments.
How do germ cells choose their sex? Drosophila as a paradigm
Authors: Steinmann‐Zwicky Monica 
Published: February 2005

AbstractSex determination in the germ line may either rely on cell‐autonomous genetic information, or it may be imposed during development by inductive somatic signals. In Drosophila, both mechanisms contribute to ensure that germ cells are oogenic when differentiating in females and spermatogenic when differentiating in males. Some of the genes that are involved in germ line sex determination have been identified. In other species, including vertebrates, inductive signals are commonly used to determine the sex of germ cells.
What the papers say: p53 Loss of Function: Implications for the Processes of Immortalization and Tumorigenesis
Authors: Finlay Cathy A. 
Published: February 2005

AbstractThe complex process of cell immortalization and transformation is likely to involve the inactivation of growth regulatory genes. Mutations (deletions, missense mutations) in the p53 gene are the most frequently observed genetic alteration in human tumors, making p53 a candidate for a cellular protein involved in the control of cell growth. Two recent studies have examined the role of p53 in immortalization and tumorigenesis(27,28). In the first study(27), p53 expression was examined in both mortal and immortal chick embryo fibroblasts. All mortal clones expressed p53 but the loss of wild‐type p53 expression was observed in every immortal cell line examined. In the second study(28), a line of mice carrying two null p53 alleles has been created and characterized. Although these mice develop normally, they show a predisposition to develop a variety of neoplasms at an early age (< 6 months). Although it is unclear whether p53 regulates the same, different, or overlapping pathways in the two experimental systems, these data demonstrate that p53 function is critical for the maintenance of normal growth control and support the current classification of p53 as a growth suppressive or tumor suppressor gene.
HNF1, a homeoprotein member of the hepatic transcription regulatory network
Authors: Tronche Françlois , Yaniv Moshe 
Published: February 2005

AbstractNumerous liver specific genes are transcriptionally activated by the binding to their promoter or enhancer of Hepatic Nuclear Factor 1 (HNF1). HNF1 contains a variant homeo‐domain and binds to DNA as either a homod‐imer or a heterodimer with the vHNF1 protein. Surprisingly, HNF1 is not restricted to hepatocytes but is expressed in epithelial cells of several endoderm derived organs and in mesoderm derived kidney tubules. Hence, HNF1 alone can not account for the differentiated state of the hepatic cells. In fact, several other liver‐enriched transcription factors have been cloned. The hepatic phenotype could result from the combinatorial. expression of these regulators. Possible involvement of these trans‐acting factors in liver organogenesis and hepatic differentiation is discussed.
The interaction of transcription factors with nucleosomal DNA
Authors: Hayes Jeffrey J. , Wolffe Alan P. 
Published: February 2005

AbstractNucleosome positioning is proposed to have an essential role in facilitating the regulated transcription of eukaryotic genes. Some transcription factors can bind to DNA when it is appropriately wrapped around the histone core, others cannot bind due to the severe deformation of DNA structure. The staged assembly of nucleosomes and positioning of histone‐DNA contacts away from promoter elements can facilitate the access of transcription factors to DNA. Positioned nucleosomes can also facilitate transcription through providing the appropriate scaffolding to bring regulatory factors bound at dispersed sites into juxtaposition.
Mesoderm induction and axis determination in Xenopus laevis
Authors: Dawid Igor B. 
Published: February 2005

AbstractIn Xenopus, as in all amphibians and possibly in vertebrate embryos in general, mesoderm formation and the establishment of the dorsoventral axis depend on inductive cell interactions. Molecules involved in mesoderm induction include FGF which acts predominantly as a ventrolateral inducer, the TGF‐β homolog activin which can induce all types of mesoderm, and members of the Wnt family which have powerful dorsalizing effects. Early effects of inducer action include the activation of regulatory genes. Among such genes, particular interest is focused on three genes encoding putative transcription factors that are expressed specifically in the Spemann organizer region of the gastrula. Expression of one of these genes, goosecoid, has been shown to be sufficient to elicit the formation of a dorsal axis including head and notochord in the embryo.
Alzheimer's disease untangled
Authors: Crawford Fiona , Goate Alison 
Published: February 2005

AbstractThe last year has seen major advances in the study of Alzheimer's disease (AD).† Four mutations involving amino acid substitutions in axons 16 and 17 of the amyloid precursor protein (APP) gene, have been identified which co‐segregate with the disease in some families multiply affected by early onset Alzheimer's disease. These mutations are strongly suggestive of a causative role for the amyloid preursor protein in Alzheimer's disease. Despite their rarity, these mutations are important because they represent the first known cause of Alzheimer's disease. Processing of APP must be central to the pathogenesis of the disease although the precise effects of these amino acid substitutions are not understood. Work is now being undertaken to characterise the processing pathways of APP and to identify other causes of AD. The development of models of AD using the APP mutations offers the possibility of identifying drug targets and developing more effective treatments than are presently available.
Phylogenetic analysis of the cadherin superfamily
Authors: Pouliot Yannick 
Published: February 2005

AbstractCadherins are a multigene family of proteins which mediate homophilic calcium‐dependent cell adhesion and are thought to play an important role in morphogenesis by mediating specific intercellular adhesion. Different lines of experimental evidence have recently indicated that the site responsible for mediating adhesive interactions is localized to the first extracellular domain of cadherin. Based upon an analysis of the sequence of this domain, I show that cadherins can be classified into three groups with distinct structural features. Furthermore, using this sequence information a phylogenetic tree relating the known cadherins was assembled. This is the first such tree to be published for the cadherins. One cadherin subtype, neural cadherin (N‐cadherin), shows very little sequence divergence between species, whereas all other cadherin subtypes show more substantial divergence, suggesting that selective pressure upon this domain may be greater for N‐cadherin than for other cadherins. Phylogenetic analysis also suggests that the gene duplications which established the main branches leading to the different cadherin subtypes occurred very early in their history. These duplications set the stage for the diversified superfamily we now observe.
Fetuin ‐ an old friend revisited
Authors: Brown W. M. , Dziegielewska K. M. , Saunders N. R. , Møsllgård K. 
Published: February 2005

AbstractBovine fetuin, the first fetal protein to be described, has recently been shown to be a species homologue of a well known human plasma protein ‐ α2HS glycoprotein (α2HS). The fetuins are now known to be members of the cystatin superfamily. The structural properties of the six fetuins that have been fully sequenced are compared. Despite the structural homology of these proteins, their described properties in the literature make them appear to be quite different. The diverse in vitro properties claimed for fetuin/α2HS are reviewed. In vivo, fetuins are involved in the acute phase response. In development, in all species studied so far, fetuins are present in a specific cell population that forms the developing neocortex. The possible functional significance of this distribution is discussed.
The hemopoietic regulators – an embarrassment of riches
Authors: Metcalf Donald 
Published: February 2005

AbstractA large, and growing, group of glycoprotein regulators is now recognized to control the proliferation, maturation and functional activity of the eight major families of blood cells. Each hemopoietic regulator is the product of multiple cell types and there is a puzzling redundancy of regulators able to stimulate each subfamily of hemopoietic cells. Each regulator is polyfunctional but it remains unclear how a single type of activated receptor is able to initiate the diverse cellular responses induced.
Control of steroid receptor function and cytoplasmic‐nuclear transport by heat shock proteins
Authors: Pratt William B. 
Published: February 2005

AbstractAs targeted proteins that move within the cell, the steroid receptors have become very useful probes for understanding the linked phenomena of protein folding and transport. From the study of steroid receptor‐associated proteins it has become clear over the past two years that these receptors are bound to a multiprotein complex containing at least two heat shock proteins, hsp90 and hsp56. Attachment of receptors to this complex in a cell‐free system appears to require the protein unfolding/folding activity of a third heat shock protein, hsp70. Like the oncogenic tyrosine kinase pp60src, steroid receptors bind to this complex of chaperone proteins at the time of their translation. Binding of the receptor to the hsp90 component of the system occurs through the hormone binding domain and is under strict hormonal control. The hormone binding domain of the receptor acts as a transferable regulatory unit that confers both tight hormonal control and hsp90 binding onto chimaeric proteins. The model of folding and transport being developed for steroid receptors leads to some general suggestions regarding the folding and transport of targeted proteins in the cell.
Retinoic acid and craniofacial development: Molecules and morphogenesis
Authors: Morriss‐Kay Gillian 
Published: February 2005

AbstractRetinoic acid (RA), a derivative of vitamin A, is essential for normal mammalian development. Developmental abnormalities induced by RA excess and vitamin A deficiency are different even though they affect the same organ systems, and it is clear that there are intraembryonic tissue differences in the requirement for RA. The developmental functions of RA are mediated by its effects on gene expression. In the nucleus, two different forms of RA bind to and activate two families of nuclear receptors, which themselves co‐operate in initiating the transcription of target genes. In this article I propose that the amount of RA reaching the nucleus in different embryonic tissues is modulated by a mechanism involving three cytoplasmic binding proteins for retinol (CRBP I) and retinoic acid (CRABP I and II). Abnormalities of craniofacial development resulting from exposure of early neural plate stage embryos to RA excess have been studied in some detail; their initial stages involve alteration of both morphological development and the segment‐specific pattern of gene expression in the early hindbrain and its derived neural crest. This system is ideal for studying the relationships between retinoic acid receptors, retinoid binding proteins, and the development of genetic and morphological pattern.
Genes and genomes: Towards construction of an overlapping YAC library of the Arabidopsis thaliana genome
Authors: Schmidt Renate , Dean Caroline 
Published: February 2005

AbstractArabidopsis thaliana (Thale cress, Arabidopsis) is an ideal model organism for the molecular genetic analysis of many plant processes. The availability of a complete physical map would greatly facilitate the gene cloning steps in these studies. The small genome size of Arabidopsis makes the construction of such a map a feasible goal. One of the approaches to construct an overlapping library of the Arabidopsis genome takes advantage of the many mapped markers and the availability of Arabidopsis yeast artificial chromosome (YAC) libraries. Mapped molecular markers are used to identify corresponding YAC clones and thereby place them on the genetic map. Subsequently, these YAC clones provide the framework for directed walking experiments aimed at closing the gaps between the YAC contigs. Adopting this strategy, YAC clones comprising about 10% of the genome have been assigned to the top halves of Arabidopsis chromosomes 4 and 5. Extensive walking experiments in a 10 cM interval of chromosome 4 have resulted in two contiguous regions in the megabase size range.
Translational regulation by mRNA/protein interactions in eukaryotic cells: Ferritin and beyond
Authors: Melefors Öjar , Hentze Matthias W. 
Published: February 2005

AbstractThe expression of certain eukaryotic genes is – at least in part – controlled at the level of mRNA translation. The step of translational initiation represents the primary target for regulation. The regulation of the intracellular iron storage protein ferritin in response to iron levels provides a good example of translational control by a reversible RNA/protein interaction in the 5' untranslated region of an mRNA. We consider mechanisms by which mRNA/protein interactions may impede translation initiation and discuss recent data suggesting that the ferritin example may represent the ‘tip of the iceberg’ of a more general theme for translational control.
Environmental regulation of virulence factors in Bordetella species
Authors: Scarlato Vincenzo , Aricó Beatrice , Domenighini Mario , Rappuoli Rino 
Published: February 2005

AbstractMany bacteria respond in a coordinate manner to environmental changes. External stimuli, sensed by receptors, are transduced to regulatory proteins which participate in well defined pathways of gene expression by varying their structure and mode of action. The network of environmental signal transduction is responsible for a fine and continuous communication between the host and the pathogenic bacteria. As a result, the gene expression machinery of the pathogen is modified continuously, in order to establish the optimal conditions for bacterial survival and multiplication.
Urokinase and urokinase receptor: A paracrine/autocrine system regulating cell migration and invasiveness
Authors: Blasi Francesco 
Published: February 2005

AbstractUrokinase and its receptor are essential components of the cell migration machinery, providing an inducible, transient and localized cell surface proteolytic activity. This activity has been shown to be required in normal and pathological forms of cellular invasiveness (i.e. in several embryonic developmental processes, during inflammatory responses and cancer metastasis and spreading). It represents one of the best known of the protcolytic systems which are currently under investigation in this field. The urokinase receptor allows a continuous regulation of the proteolytic activity at cell contacts, utilizing the different localization of urokinase and its inhibitors. The receptor, in fact, in addition to focusing the enzymatic activity at focal and cell‐cell contacts, also regulates it by internalizing and degrading only the inhibited form of urokinase. Internalized receptor releases the ligands to the lysosomes and recycles back to surface. In this way, the proteolytically active areas of the cell surface can be continuously monitored for their activity and their location modified. The cell can thus coordinate its migration efforts with a step‐wise modification of the proteolytic activity‐map of the cell surface. The urokinase cycle can be supported by one individual cell (autocrine) or by two or more cells. In the latter case, complementation and synergism of urokinase and its receptor are found.