bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of MCM proteins in the cell cycle control of genome duplication
Authors: Kearsey Stephen E. , Maiorano Domenico , Holmes Eddie C. , Todorov Ivan T. 
Published: February 2005

AbstractThe regulatory mechanism which ensures that eukaryotic chromosomes replicate precisely once per cell cycle is a basic and essential cellular property of eukaryotes. This fundamental aspect of DNA replication is still poorly understood, but recent advances encourage the view that we may soon have a clearer picture of how this regulation is achieved. This review will discuss in particular the role of proteins in the minichromosome maintenance (MCM) family, which may hold the key to understanding how DNA is replicated once, and only once, per cell cycle.
UV damage and repair mechanisms in mammalian cells
Authors: Tornaletti Silvia , Pfeifer Gerd P. 
Published: February 2005

AbstractThe formation of DNA photoproducts by ultraviolet (UV) light is responsible for induction of mutations and development of skin cancer. To understand UV mutagenesis, it is important to know the mechanisms of formation and repair of these lesions. Cyclobutane pyrimidine dimers and (6–4)photoproducts are the two major classes of UV‐induced DNA lesions. Their distribution along DNA sequences in vivo is strongly influenced by nucleosomes and other DNA binding proteins. Repair of UV photoproducts is dependent on the transcriptional status of the sequences to be repaired and on the chromatin environment. Sensitive techniques are now available to study repair of UV damage at the level of nucleotide resolution in mammalian cells. With the aid of in vitro systems, the entire nucleotide excision repair process has been reconstituted from purified protein components with naked DNA as a substrate. Future work will focus on the development of in vitro assays for transcription‐coupled repair and repair in chromatin.
Involvement of the neuregulins and their receptors in cardiac and neural development
Authors: Carraway Kermit L. 
Published: February 2005

AbstractThe neuregulin gene encodes a series of polypeptide growth factors that can influence the growth state of target vertebrate cells in culture. Recently, three studies have explored the in vivo function of the neuregulin signaling system in mice by disrupting the genes encoding the neuregulin ligand(1) and two of its receptors, ErbB2(2) and ErbB4(3). Each of the genes is essential for development, and aberrations in cardiac and neural development are particularly prominent in mutant embryos. The observed defects, together with the localization of expression of the neuregulin signaling components within these tissues, highlight a paracrine mechanism for neuregulin‐mediated intercellular communication.
Hierarchical guidance cues in the developing nervous system of C. elegans
Authors: Wadsworth William G. , Hedgecock Edward M. 
Published: February 2005

AbstractDuring embryogenesis, the basic axon scaffold of the nervous system is formed by special axons that pioneer pathways between groups of cells. To find their way, the pioneer growth cones detect specific cues in their extracellular environment. One of these guidance cues is netrin. Observations and experimental manipulations in vertebrates and nematodes have shown that netrin is a bifunctional guidance cue that can simultaneously attract and repel axons. During the formation of this basic axon scaffold in Caenorhabditis elegans, the netrin UNC‐6 is expressed by neuroglia and pioneer neurons, providing hierarchical guidance cues throughout the animal. Each cue has a characteristic role depending on the cell type, its position and the developmental stage. These roles include activities as global, decussation and labeled‐pathway cues. This hierarchical model of UNC‐6 netrin‐mediated guidance suggests a method by which guidance cues can direct formation of basic axon scaffolds in developing nervous systems.
Meiotic recombination: A mechanism for tracking and eliminating mutations?
Authors: McKee Bruce D. 
Published: February 2005

AbstractThe function of meiotic recombination has remained controversial, despite recent inroads into mechanisms. Ideas concerning a possible role of recombination in the elimination or efficient incorporation of mutations have been backed by theoretical studies but have lacked empirical support. Recent investigations into the basis for local variations in recombination frequency in yeast have uncovered a strong association between recombination initiation sites and transcriptional regulatory sequences. Other recent studies indicate a strong correlation between transcription and mutation rates in yeast genes. Taken together, these data imply that distributions of recombination and mutation frequencies may be strongly correlated. This suggests that recombination may be targeted to genomic sites of high mutation frequency; such a ‘mutation‐tracking’ function would clearly aid in the shuffling of mutations to break up unfavorable and create favorable allelic combinations. Moreover, recent insights into the mechanism of gene conversion in yeast reveal a very strong inherent bias in favor of alleles on the non‐initiating homolog. Combined with mutation tracking, these findings suggest a novel and general mechanism by which allelic gene conversion may act to eliminate mutations.
Genes, cellular interactions and cell lineages in the determination of plant trichome spacing
Authors: Sachs Tsvi 
Published: February 2005

AbstractConceptual developments have defined concrete questions about the timing and precise location of cellular pattern formation. Plants in general, and the trichomes of Arabidopsis in particular, are remarkably suited for research on these problems. Genetic analysis requires the quantitative characterizations of the developmental processes by which patterning occurs. Larkin et al.(1) have provided measures of the non‐random distances between trichomes. They have also obtained evidence about the cell lineages leading to trichome development, and this evidence constrains the possible role of intracellular programs. Continued genetic analysis may call for the identification of mutations that are expressed only during development and whose effects are corrected before the phenotype matures.
Green life: Control of chloroplast gene transcription
Authors: Link Gerhard 
Published: February 2005

AbstractChloroplasts and other plastids are plant cell organelles that account for major biochemical functions. They contain their own gene expression system but are integrated into the signaling network of the entire cell. Both nuclear and plastid genes are involved in chloroplast biogenesis, and the gene expression pathways both inside and outside the organelle are subject to developmental and environmental control. The plastid transcription apparatus reflects this general scheme, with a basic organelle‐encoded enzymatic machinery surrounded by factors that may be encoded by nuclear genes. Among the transcription regulatory mechanisms thought to play a role during plastid development are: (1) differential usage of promoter elements; (2) phosphorylation of transcription factors by a protein kinase, which is itself subject to phosphorylation and redox control; (3) dynamic changes in the composition of the transcription apparatus. In etioplasts, the dominating polymerase ‘B’ is a bacterial‐type enzyme, whereas the major chloroplast polymerase ‘A’ is a much larger enzyme reminiscent of those in the nucleus. These two enzyme forms may share common components and recruit others during development.
Control and integration of cell signaling pathways during C. Elegans vulval development
Authors: Sundaram Meera , Han Min 
Published: February 2005

AbstractVulval development in the Caenorhabditis elegans hermaphrodite represents a simple, genetically tractable system for studying how cell signaling events control cell fata decisions. Current models suggest that proper specification of vulval cell fates relies on the integration of multiple signaling systems, including one that involves a receptor tyrosine kinase (RTK)→Ras→mitogen activated protein kinase (MAPK) cascade and one that involves a LIN‐12/Notch family receptor. In this review, we first discuss how genetic strategies are being used to identify and analyze components that control vulval cell fate decisions. We then describe the different signaling systems that have been elucidated and how they relate to one another. Finally, we highlight several recently characterized genes that encode positive regulators, negative regulators or potential targets of the RTK→Ras→MAPK cascade involved in vulval induction.
Is something wrong with the tree of life?
Authors: Martin William F. 
Published: February 2005

AbstractA recent study(1) of sequence data from many different proteins has suggested that contemporary prokaryotes and eukaryotes may have shared a common ancestor as recently as 2 billion years ago (the molecular clock). Strong evidence from the geological record, however, indicates that oxygen‐producing microorganisms, perhaps similar to modern cyanobacteria, existed 3.5 billion years ago. The fossil evidence, therefore, suggests that any common ancestor of prokaryotes and eukaryotes must have existed at least 1.5 billion years earlier than suggested by the molecular clock evidence. The discrepancy between molecular and geological evidence for the age of modern cells is considered here, as are aspects of gene descent in the tree of life that might help to account for it.
Modulation by nitric oxide of metalloprotein regulatory activities
Authors: Drapier Jean‐Claude , Bouton CéCile 
Published: February 2005

AbstractIn many cells, a nitric oxide (NO) synthase inducible by immunological stimuli produces a sustained flow of NO that lasts a long time. NO is a short‐lived molecule but it is a diffusibel ligand believed to be capable of reaching distal target sites. Further, several lines of evidence indicate that cysteine‐rich motifs of metal‐binding proteins, as well as redox‐sensitive metal clusters of metalloproteins, are natural sensors of bioradicals like NO. In metalloregulatory proteins, metals are often conveniently located at binding sites and bound to cysteine residues. Accordingly, disruption of the metal‐thiolate polymetallic clusters should trigger significant remodelling of the protein structure involved in regulation. We can therefore postulate that the nitrosation reaction occurring at metal centres or cysteine‐rich motifs will preclude correct binding to regulatory sites. Several examples are given of metalloregulatory proteins whose metal is bound to thiols and may then become sensitive to NO. Recent observations indicate that in response to NO synthesis, iron regulatory protein, a eukaryotic bifunctional [Fe‐S] protein, switches from acting as aconitase to being an RNA‐binding regulator, and we suggest that the interplay between NO or a NO‐derived molecule and metal clusters at critical allosteric sites may be a crucial component of the cellular response to environmental stress.
Cytokinins in plant senescence: From spray and pray to clone and play
Authors: Gan Susheng , Amasino Richard M. 
Published: February 2005

AbstractThree approaches have been used to investigate the inhibitory role of the cytokinin class of phytohormones in plant senescence: external application of cytokinins, measurement of endogenous cytokinin levels before and during senescence, and manipulation of endogenous cytokinin production in transgenic plants. In transgenic plant studies, endogenous cytokinin levels are manipulated by expression of IPT, a gene encoding isopentenyl transferase. Transgenic plants expressing IPT from a variety of promoters exhibit developmental and morphological alterations and often display retarded leaf senescence. A recently developed autoregulatory senescence‐inhibition system targets cytokinin production quantitatively, spatially and temporally, and results in transgenic plants that exhibit significantly delayed senescence without abnormalities. These transgenic studies not only confirm the regulatory role of cytokinins in plant senescence, but also provide a way to manipulate senescence for potential agricultural applications.
Protein kinase cascades activated by stress and inflammatory cytokines
Authors: Kyriakis John M. , Avruch Joseph 
Published: February 2005

AbstractSignal transduction pathways constructed around a core module of three consecutive protein kinases, the most distal being a member of the extracellular signal‐regulated kinase (ERK) family, are ubiquitous among eukaryotes. Recent work has defined two cascades activated preferentially by the inflammatory cytokines TNF‐α and IL‐1‐β, as well as by a wide variety of cellular stresses such as UV and ionizing radiation, hyperosmolarity, heat stress, oxidative stress, etc. One pathway converges on the ERK subfamily known as the ‘stress activated’ protein kinases (SAPKs, also termed Jun N‐terminal kinases, JNKs), whereas the second pathway recruits the p38 kinases. Upstream inputs are diverse, and include small GTPases (primarily Rac and Cdc42; secondarily Ras) acting through mammalian homologs of the yeast Ste20 kinase, other kinase subfamilies (e.g. GC kinase) and ceramide, a putative second messenger for certain TNF‐α actions. These two cascades signal cell cycle delay, cellular repair or apoptosis in most cells, as well as activation of immune and reticuloendothelial cells.
A new lease of life for an old enzyme
Authors: Martini Giuseppe , Ursini Matilde Valeria 
Published: February 2005

AbstractWe review here some recent data about glucose‐6‐phosphate dehydrogenase (G6PD), the first and key regulatory enzyme of the pentose phosphate pathway. New evidence has been presented to suggest that malaria is a selective agent for G6PD deficiency, which is the most common enzymopathy in man, and that G6PD deficiency, generally considered to be a mild and benign condition, is significantly disadvantageous in certain environmental conditions. At the molecular level, the enzyme structure has recently been elucidated and mechanisms regulating G6PD gene expression have been determined. A G6PD knock‐out mutation introduced in mouse cells makes them exquisitely sensitive to oxidative stress, indicating that this ubiquitous metabolic enzyme has a major role in the defence against oxidative stress, even in eukaryotic nucleated cells, which have several alternative routes for providing the same protection. Because of the high prevalence of G6PD deficiency in many populations, it is expected that these findings will prompt further studies to ascertain the putative role of G6PD deficiency in conditions such as carcinogenesis and ageing.
A new role for the stromal cells in kidney development
Authors: Bard Jonathan 
Published: February 2005

AbstractNew observations by Hatini et al.(1) on the ‘winged helix’ transcription factor BF‐2 will make us change our views about kiney development. This gene is only expressed in stromal cells associated with the kidney medulla and cortex, but the BF‐2 knockout has unexpected abnormalities. Although the stromal cells appear normal, the kidney is small, the ducts have limited branching and, instead of the many normal nephrogenic aggregates, there are relatively few large mesenchymal aggregates that fail to differentiate. The stromal cells thus seem to produce factors regulating other aspects of kidney development, while the abnormalities highlight a series of unsolved problems in kidney morphogenesis.
The cellular internet: On‐line with connexins
Authors: Bruzzone Roberto , White Thomas W. , Goodenough Daniel A. 
Published: February 2005

AbstractMost cells communicate with their immediate neighbors through the exchange of cytosolic molecules such as ions, second messengers and small metabolites. This activity is made possible by clusters of intercellular channels called gap junctions, which connect adjacent cells. In terms of molecular architecture, intercellular channels consist of two channels, called connexons, which interact to span the plasma membranes of two adjacent cells and directly join the cytoplasm of one cell to another. Connexons are made of structural proteins named connexins, which compose a multigene family. Connexin channels participate in the regulation of signaling between developing and differentiated cell types, and recently there have been some unexpected findings. First, unique ionic‐ and size‐selectivities are determined by each connexin; second, the establishment of intercellular communication is defined by the expression of compatible connexins; third, the discovery of connexin mutations associated with human diseases and the study of knockout mice have illustrated the vital role of cell‐cell communication in a diverse array of tissue functions.
Myelin mutants: Model systems for the study of normal and abnormal myelination
Authors: Griffiths Ian R. 
Published: February 2005

AbstractSpontaneous mutations that perturb myelination occur in a range of species including man, and together with engineered mutations have been used to study disease, normal myelination and axon/glial inter‐relationships. Only a minority of the currently defined mutations have an apparently simple pathogenesis due to lack of a functional protein. Mutations in the myelin basic protein gene lead to a lack of protein, resulting in changes in the structure of myelin, which can be rescued by transgenic complementation. The pathogenesis of autosomal dominant and X‐linked mutations affecting either oligodendrocytes or Schwann cells is more complex. Point mutations may act in a dominant negative manner and gene dosage is clearly linked to phenotypic change. Mutations in regulatory genes, such as those encoding transcription factors, can also disturb myelination by selected cell types. Other less‐well studied and unexpected consequences of myelin mutations, such as seizures in mutations affecting genes expressed in Schwann cells and axonal changes associated with dysmyelination, are also considered. With the major developments in gene mapping and cloning it is now relevant to study mutations in a variety of species with the real prospect of defining their molecular basis. Examples are given of unusual, but potentially useful, uncharacterised mutations in dog and bovine.
Dynamin GTPase, a force‐generating molecular switch
Authors: Warnock Dale E. , Schmid Sandra L. 
Published: February 2005

AbstractDynamin is a GTPase that regulates late events in clathrin‐coated vesicle formation. Our current working model suggests that dynamin is targeted to coated pits in its unoccupied or GDP‐bound form, where it is initially distributed uniformly throughout the clathrin lattice. GTP/GDP exchange triggers its release from these sites and its assembly into short helices that encircle the necks of invaginated coated pits like a collar. GTP hydrolysis, which is required for vesicle detachment, presumably induces a concerted conformation change, tightening the collar. Unlike most of its GTPase cousins that serve as molecular switches, dynamin has a low affinity for GTP, a very high intrinsic rate of GTP hydrolysis and functions as a homo‐oligomer. A concerted conformational change resulting from coordinated GTP hydrolysis by the dynamin oligomer might be sufficient to generate force. In this case, dynamin would be the first GTPase identified that acts as a structural protein with mechano‐chemical function.
Cooperation between soluble factors and integrin‐mediated cell anchorage in the control of cell growth and differentiation
Authors: Juliano Rudy 
Published: February 2005

AbstractRecently it has become clear that integrins and other adhesive receptors play an important role in the control of cell growth and differentiation. In various cell types, anchorage to the extracellular matrix via integrins strongly influences the ability of the cell to respond to soluble mitogens or to differentiation factors. Thus adhesive receptors must generate signals that influence cell behavior. Some of the pathways of adhesion receptor signaling are now beginning to be worked out, but there is still much to learn. In particular, the mechanistic basis for the cooperation between anchorage signals and signals from soluble growth and differentiation factors remains ill‐defined. This review will examine some of the current information linking adhesion receptors to control of mitogenesis and differentiation.
Archaebacterial genomics: The complete genome sequence of Methanococcus jannaschii
Authors: Edgell David R. , Doolittle W. Ford 
Published: February 2005

AbstractThe first complete sequence of an archaebacterial genome, that of Methanococcus jannaschii, has recently been published(1). Less than half of the open reading frames (ORFs) can be assigned a function based on similarity to known sequences in databases. These assignable ORFs fall into two general classes; those involved in transcription, translation and replication are more similar to eukaryotic homologs, while those determining metabolic processes are more similar to eubacterial versions. The immense but very rewarding task of making biological and evolutionary sense of all this information has only just begun.
Synthesis and function of mos: The control switch of vertebrate oocyte meiosis
Authors: Gebauer Fátima , Richter Joel D. 
Published: February 2005

AbstractOne distinguishing feature of vertebrate oocyte meiosis is its discontinuity; oocytes are released from their prophase I arrest, usually by hormonal stimulation, only to again halt at metaphase II, where they await fertilization. The product of the c‐mos proto‐oncogene, Mos, is a key regulator of this maturation process. Mos is a serine‐threonine kinase that activates and/or stabilizes maturation‐promoting factor (MPF), the master cell cycle switch, through a pathway that involves the mitogen‐activated protein kinase (MAPK) cascade. Oocytes arrested at prophase I lack detectable levels of Mos, which must be synthesized from a pool of maternal mRNAs for proper maturation. While Mos is necessary throughout maturation in Xenopus, it seems to be required only for meiosis II in the mouse. The translational activation of c‐mos mRNA at specific times during meiosis requires cytoplasmic polyadenylation. Cis‐ and trans‐acting factors for polyadenylation are, therefore, essential elements of maturation.
Integrin‐mediated calcium signaling and regulation of cell adhesion by intracellular calcium
Authors: Sjaastad Michael D. , Nelson W. James 
Published: February 2005

AbstractIntegrins are ubiquitous trans‐membrane adhesion molecules that mediate the interaction of cells with the extracellular matrix (ECM). Integrins link cells to the ECM by interacting with the cell cytoskeleton. In cases such as leukocyte binding, integrins mediate cell‐cell interactions and cell‐ECM interactions. Recent research indicates that integrins also function as signal transduction receptors, triggering a number of intracellular signaling pathways that regulate cell behavior and development. A number of integrins are known to stimulate changes in intracellular calcium levels, resulting in integrin activation. Although changes in intracellular calcium regulate a vast number of cellular functions, this review will discuss the stimulation of calcium signaling by integrins and the role of intracellular calcium in the regulation of integrin‐mediated adhesion.