bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specification of cell fate in the developing eye of Drosophila
Authors: Basler Konrad , Hafen Ernst 
Published: February 2005

AbstractDetermination of cell fate in the developing eye of Drosophila depends on a precise sequence of cellular interactions which generate the stereotypic array of ommatidia. In the eye imaginal disc, an initially unpatterned epithelial sheath of cells, the first step in this process may be the specification of R8 photoreceptor cells at regular intervals. Genes such as Notch and scabrous, known to be involved in bristle development, alos participate in this process, suggesting that the specification of ommatidial founder cells and the formation of sensory organs in the adult epidermis may involve a similar mechanism, that of lateral inhibition. The subsequent steps of ommatidial assembly, following R8 assignment, involve a different mechanism: Undetermined cells read their position based on the contacts they make with neighbors that have already begun to differentiate. The development of the R7 photoreceptor cell, one of the eight photoreceptor cells in the ommatidium, is best understood. An important role seems to be played by sevenless, a receptor tyrosine kinase on the surface of the R7 precursor. It transmits the positional information– most likely encoded by the boss protein on the neighboring R8 cell membrane – into the cell via its tyrosine kinase, which activates a signal transduction cascade. Constitutive activation of the sevenless kinase by overexpression of an N‐terminally truncated form results in the diversion of other ommatidial cells into the R7 pathway suggesting that activation of the sevenless signalling pathway is sufficient to specify R7 development. Genetic dissection of this pathway should therefore identify components of a signalling cascade activated by a tyrosine kinase.
The prenylation of proteins
Authors: Sinensky Michael , Lutz Robert J. 
Published: February 2005

AbstractThe prenylated proteins represent a newly discovered class of post‐translationally modified proteins. The known prenylated proteins include the oncogene product p21ras and other low molecular weight GTP‐binding proteins, the nuclear lamins, and the γ subunit of the heterotrimeric G proteins. The modification involves the covalent attachment of a 15‐carbon (farnesyl) or 20‐carbon (geranylgeranyl) isoprenoid moiety in a thioether linkage to a carboxyl terminal cysteine. The nature of the attached substituent is dependent on specific sequence information in the carboxyl terminus of the protein. In addition, prenylation entrains other post‐translational modifications forming a reaction pathway. In this article, we review our current understanding of the biochemical reactions involved in prenylation and discuss the possible role of this modification in the control of cellular functions such as protein maturation and cell growth.
Chromosome motion in mitosis
Authors: Gorbsky Gary J. 
Published: February 2005

AbstractThe nature of the forces that move chromosomes in mitosis is beginning to be revealed. The kinetochore, a specialized structure situated at the primary constriction of the chromosome, appears to translocate in both directions along the microtubules of the mitotic spindle. One or more members of the newly described families of microtubule motor molecules may power these movements. Microtubules of the mitotic spindle undergo rapid cycles of assembly and disassembly. These microtubule dynamics may contribute toward generating force and regulating direction in chromosome movement.
The end of the message: 3'– end processing leading to polyadenylated messenger RNA
Authors: Wahle Elmar 
Published: February 2005

AbstractAlmost all messenger RNAs carry a polyadenylate tail that is added in a post‐transcriptional reaction. In the nuclei of animal cells, the 3'‐end of the RNA is formed by endonucleolytic cleavage of the primary transcript at the site of poly (A) addition, followed by the polymerisation of the tail. The reaction depends on specific RNA sequences upstream as well as downstream of the polyadenylation site. Cleavage and polyadenylation can be uncoupled in vitro. Polyadenylation is carried out by poly(A) polymerase with the aid of a specificity factor that binds the polyadenylation signal AAUAAA. Several aditional factors are required for the initial cleavage. A newly discovered poly(A)‐binding protein stimulates poly(A) tail synthesis and may be involved in the control of tail length. Polyadenylation reactions different from this scheme, either in other organisms or under special physiological circumstances, are discussed.
What determines the instability of c‐myc proto‐oncogene mRNA?
Authors: Laird‐Offringa Ite A. 
Published: February 2005

AbstractThe c‐myc proto‐oncogene is believed to be involved in the regulation of cell growth and differentiation. Deregulation of this gene, resulting in an inappropriate increase of gene product, can contribute to cancer formation. One of the ways in which the expression of the c‐myc gene can be deregulated is by the stabilization of the labile c‐myc mRNA. The rapid degradation of the c‐myc transcript appears to be mediated by at least two distinct regions in the mRNA. One lies in the 3' untranslated region, and presumably consists of (A+U)‐rich sequences. The other lies in the C‐terminal part of the coding region and colocalizes with sequences encoding protein‐dimerization motifs. The exact mechanism by which the destabilizing elements function is not yet clear. Shortening of the poly(A) tail of the c‐myc message appears to precede degradation of the transcript. When translation is blocked, this shortening is slowed down and the mRNA is stabilized. This suggests that deadenylation is required before degradation of the mRNA body can take place.
Problems and paradigms: Dynamic lipid‐bilayer heterogeneity: A mesoscopic vehicle for membrane function?
Authors: Mouritsen Ole G. , Jørgensen Kent 
Published: February 2005

AbstractThe lipid‐bilayer component of cell membranes is an aqueous bimolecular aggregate characterized by a heterogeneous lateral organization of its molecular constituents. The heterogeneity may be sustained statically as well as dynamically. On the basis of recent experimental and theoretical progress in the study of the physical properties of lipid‐bilayer membranes, it is proposed that the dynamically heterogeneous membrane states are important for membrane functions such as transport of matter across the membrane and enzymatic activity. The heterogeneous membrane states undergo significant structural changes in response to changes in compositional, thermodynamic, and environmental conditions. The diverse effects of a variety of molecular Compounds interacting with membranes, such as Cholesterol and drugs like anaesthetics, may be understood in terms of the ability of these compounds to affect and modulate the dynamic membrane heterogeneity.
What the papers say: Protein folding pathways determined using disulphide bonds
Authors: Creighton Thomas E. 
Published: February 2005

AbstractThe best‐characterized model pathway of protein folding, that of disulphide bond formation in the small protein BPTI, has been questioned recently. A reinvestigation of that pathway, using alternative methods, concluded that the intermediates with non‐native disulphide bonds accumulated to lower levels than previously had been observed(17). On this basis, a revised pathway was proposed that simply omitted those intermediates. Even if totally correct, however, the new observations are not inconsistent with the important characteristics of the original pathway and even confirmed many of them. Certain crucial observations that were the experimental basis for the original pathway were ignored, and these observations invalidate the revised pathway.
Evolution of alternate modes of development in ascidians
Authors: Jeffery William R. , Swalla Billie J. 
Published: February 2005

AbstractAscidians have evolved alternate modes of development in which the conventional tadpole larva is remodeled or eliminated. Adultation, the precocious development of adult features in the larval head, is caused by superimposing the larval and adult differentiation programs. Caudalization, the addition of muscle cells to the larval tail, is caused by enhancing muscle induction or increasing the number of muscle cell divisions before terminal differentiation. Adultation and caudalization are correlated with increased egg size, suggesting dependence on maternal processes. Anural development, the elimination of the larval stage, is caused by maternal and zygotic events resulting in abbreviation and deletion of larval developmental programs. An example of a maternal change in anural species is the modification of the egg cytoskeleton during oogenesis, whereas a zygotic change may involve altered cell interactions during embryogenesis. Interspecific hybridization experiments suggest that some aspects of anural development may be caused by loss‐of‐function mutations. The dissociation of developmental programs is a key process in changing the mode of development in ascidians.
Problems and paradigms: Redundancies, development and the flow of information
Authors: Tautz Diethard 
Published: February 2005

AbstractThere is increasing evidence for the wide‐spread existence of functionally redundant genetic pathways in developmental processes. However, both their significance and manner of evolution are still matters of debate. I will argue here that redundancy of gene actions may, in fact, be a necessary requirement for the development and evolution of complex life forms. One can view development as a process that transmits information from the egg to the adult organism. Transmission of information is, however, always an error‐prone process, which can only be safeguarded by including redundancies in the message. Molecular examples for well analysed redundant processes indicate that redundancies may best be understood within a conceptual framework of overlaps between different gene functions.
Problems and paradigms: Hoemeobox genes in vertebrate evolution
Authors: Holland Peter 
Published: February 2005

AbstractA wide range of anatomical features are shared by all vertebrates, but absent in our closest invertebrate relatives. The origin of vertebrate embryogenesis must have involved the evolution of new regulatory pathways to control the development of new features, but how did this occur? Mutations affecting regulatory genes, including those containing homeobox sequences, may have been important: for example, perhaps gene duplications allowed recruitment of genes to new roles. Here I ask whether comparative data on the genomic organization and expression patterns of homeobox genes support this hypothesis. I propose a model in which duplications of particular homeobox genes, followed by the acquisition of gene‐specific secondary expression domains, allowed the evolution of the neural crest, extensive organogenesis and craniofacial morphogenesis. Specific details of the model are amenable to testing by extension of this comparative approach to molecular embryology.
The molecular basis of the type 1 glycogen storage diseases
Authors: Burchell Ann 
Published: February 2005

AbstractMicrosomal glucose‐6‐phosphatase catalyses the last step in liver glucose production. Glucose‐6‐phosphatase deficiency, now termed type 1 glycogen storage disease, was first described almost 40 years ago but until recently very little was known about the molecular basis of the various type 1 glycogen storage diseases. Recently we have shown that at least six different proteins are needed for normal glucose‐6‐phosphatase activity in liver. Four of the proteins have been purified and three cloned. Study of the type 1 glycogen storage diseases has stimulated investigations of the mechanisms of small molecule transport across the endoplasmic reticulum membrane and demonstrated the existence of novel endoplasmic reticulum transport proteins for glucose and phosphate.
The matrix‐degrading metalloproteinases
Authors: Matrisian Lynn M. 
Published: February 2005

AbstractThe matrix‐degrading metalloproteinases are an intriguing family of enzymes that have evolved to digest specific extracellular matrix components. The expression of these enzymes is very highly regulated and can be controlled transcriptionally by a number of growth factors, tumor promoters, oncogenes, and hormones. It is suggested that the coordinated regulation of matrix metalloproteinases and their inhibitors by these agents modify the integrity of the extracellular matrix. These modifications may, at least in part, be responsible for mediating the effects of these factors on complex physiological processes.
Is calpain activity regulated by membranes and autolysis or by calcium and calpastatin?
Authors: Goll Darrel E. , Thompson Valery F. , Taylor Richard G. , Zalewska Teresa 
Published: February 2005

AbstractAlthough the Ca2+‐dependent proteinase (calpain) system has been found in every vertebrate cell that has been examined for its presence and has been detected in Drosophila and parasites, the physiological function(s) of this system remains unclear. Calpain activity has been associated with cleavages that alter regulation of various enzyme activities, with remodeling or disassembly of the cell cytoskeleton, and with cleavages of hormone receptors. The mechanism regulating activity of the calpain system in vivo also is unknown. It has been proposed that binding of the calpains to phospholipid in a cell membrane lowers the Ca2+ concentration, [Ca2+], required for the calpains to autolyze, and that autolysis converts an inactive proenzyme into an active protease. Recent studies, however, show that the calpains bind to specific proteins and not to phospholipids, and that binding to cell membranes does not affect the [Ca2+] required for autolysis. It seems likely that calpain activity is regulated by binding of Ca2+ to specific sites on the calpain molecule, with binding to each site eliciting a response (proteolytic activity, calpastatin binding, etc.) specific for that site. Regulation must also involve an, as yet, undiscovered mechanism that increases the affinity of the Ca2+‐binding sites for Ca2+.
Mammalian origins of replication
Authors: Hamlin Joyce L. 
Published: February 2005

AbstractIt has been almost twenty‐five years since Huberman and Riggs first showed that there are multiple bidirectional origins of replication scattered at ∼100 kb intervals along mammalian chromosomal fibers. Since that time, every conceivable physical property unique to replicating DNA has been taken advantage of to determine whether origins of replication are defined sequence elements, as they are in microorganisms. The most thoroughly studied mammalian locus to date is the dihydrofolate reductase domain of Chinese hamster cells, which will be used as a model to discuss the various methods of investigation. While several laboratories agree on the rough location of the [initiation locus] in this large chromosomal domain, different experimental approaches paint different pictures of the mechanism by which initiation occurs. However, a variety of new techniques and synchronizing agents promises to clarify the picture for this particular locus, and to provide the means for identifying and isolating other origins of replication for comparison.
What have tissue culture studies told us about the development of oligodendrocytes?
Authors: Williams Brenda P. , Price Jack 
Published: February 2005

AbstractOne major success of studying neural cell development in tissue culture has been the discovery of the O‐2A cell. This bipotential cell generates oligodendrocytes or, under certain conditions, a type of astrocyte. This essay considers the evidence that the characteristic properties demonstrated by the O‐2A cells in vitro are an accurate reflection of oligodendrocyte development in vivo.
AMP‐activated protein kinase ‐ An archetypal protein kinase cascade?
Authors: Hardie D. Grahame , Mackintosh Robert W. 
Published: February 2005

AbstractMammalian AMP‐activated protein kinase is the central component of a protein kinase cascade which inactivates three key enzymes involved in the synthesis or release of free fatty acids and cholesterol inside the cell. The kinase cascade is activated by elevation of AMP, and perhaps also by fatty acid and cholesterol metabolites. The system may fulfil a protective function, preventing damage caused by depletion of ATP or excessive intracellular release of free lipids, a type of stress response. Recent evidence suggests that it may have been in existence for at least a billion years, since a very similar protein kinase cascade is present in higher plants. This system therefore represents an early eukaryotic protein kinase cascade, which is unique in that it is regulated by intracellular metabolites rather than extracellular signals or cell cycle events.
DNA synthesis control in yeast: An evolutionarily conserved mechanism for regulating DNA synthesis genes?
Authors: Merrill Gary F. , Morgan Brian A. , Lowndes Noel F. , Johnston Leland H. 
Published: February 2005

AbstractAfter yeast cells commit to the cell cycle in a process called START, genes required for DNA synthesis are expressed in late G1. Periodicity is mediated by a hexameric sequence, known as a MCB element, present in all DNA synthesis gene promoters. A complex that specifically binds MCBs has been identified. One polypeptide in the MCB complex is Swi6, a transcription factor that together with Swi4 also binds G1 cyclin promoters and participates in a positive feedback loop at START. The finding that Swi6 is directly involved in both START and DNA synthesis gene control suggest a model in which Swi6, activated through its participation in START, serves as the central transcription factor in coordinating late G1 gene expression. The mechanism may be conserved in all eukaryotic cells.
Cyclin synthesis: Who needs it?
Authors: Minshull Jeremy 
Published: February 2005

AbstractStudies of the G2 to M transition in amphibian oocytes, in combination with in vitro mitotic systems and yeast genetic analysis, have significantly contributed to our understanding of the mechanisms by which M‐phase is regulated. Historically, oocyte maturation has provided a number of valuable initial observations, but the biochemical elucidation of cell cycle control mechanisms has proved more tractable in cell‐free extracts of frog eggs which reproduce aspects of early embryogenic mitosis. Recent experiments examining the importance of protein synthesis in the maturing oocyte have highlighted some important differences between mitosis and meiosis. Additional controls found in meiosis but not embryonic mitosis, are similar to controls found in somatic cells. This suggests that understanding the differences, as well as the similarities, between meiosis in the oocyte and mitosis in the early embryo will help us to learn more about the way in which cells enter and leave mitosis.
The evolutionary history of the first three enzymes in pyrimidine biosynthesis
Authors: Davidson Jeffrey N. , Chen Kuey C. , Jamison Robert S. , Musmanno Lisa A. , Kern Christine B. 
Published: February 2005

AbstractSome metabolic pathways are nearly ubiquitous among organisms: the genes encoding the enzymes for such pathways must therefore be ancient and essential. De novo pyrimidine biosynthesis is an example of one such metabolic pathway. In animals a single protein called CADAbbreviations: CAD, trifunctional protein catalyzing the first three steps of de novo pyrimidine biosynthesis in higher eukaryotes; CPS, carbamyl phosphate synthetase domain; CPSase, carbamyl phosphate synthetase activity; ATC, aspartate transcarbamylase domain; ATCase, aspartate transcarbamylase activity; DHO, dihydroorotase domain; DHOase, dihydroorotase activity; GLN, glutaminase subdomain or subunit of carbamyl phosphate synthetase, GL Nase, glutaminase activity; SYN, synthetase subdomain or subunit of carbamyl phosphate synthetase; SYNase, synthetase activity.
carries the first three steps of this pathway. The same three enzymes in prokaryotes are associated with separate proteins. The CAD gene appears to have evolved through a process of gene duplication and DNA rearrangement, leading to an in‐frame gene fusion encoding a chimeric protein. A driving force for the creation of eukaryotic genes encoding multienzymatic proteins such as CAD may be the advantage of coordinate expression of enzymes catalyzing steps in a biosynthetic pathway. The analogous structure in bacteria is the operon. Differences in the translational mechanisms of eukaryotes and prokaryotes may have dictated the different strategies used by organisms to evolve coordinately regulated genes.
Tyrosine kinase receptors in the control of epithelial growth and morphogenesis during development
Authors: Birchmeier Carmen , Sonnenberg Eva , Weidner K. Michael , Walter Barbara 
Published: February 2005

AbstractThe c‐ros, c‐met and c‐neu genes encode receptor‐type tyrosine kinases and were originally identified because of their oncogenic potential. However, recent progress in the analysis of these receptors and their respective ligands indicate that they do not mediate exclusively mitogenic signals. Rather, they can induce cell movement, differentiation or morphogenesis of epithelial cells in culture. Interestingly, the discussed receptors are expressed in embryonal epithelia, whereas direct and indirect evidence shows that the corresponding ligands are produced in mesenchymal cells. In development, signals given by mesenchymal cells are major driving forces for differentiation and morphogenesis of epithelia; embryonal epithelia are generally unable to differentiate without the appropriate mesenchymal factors. The observed activities of these receptor/ligand systems in cultured cells and their expression patterns indicate that they regulate epithelial differentiation and morphogenesis also during embryogenesis and suggest thus a molecular basis for mesenchymal epithelial interactions.
Early human embryo metabolism
Authors: Leese Henry J. , Conaghan Joe , Martin Karen L. , Hardy Kate 
Published: February 2005

AbstractNon‐invasive microanalytical methods have been devised to study the energy metabolism of single human preimplantation embryos. Psyruvate, which is added routinely to all media used to culture human embryos, is consumed throughout the preimplantation period, with glucose assuming an increasing role at embryo compaction and blastocyst formation. All of the glucose consumed may be accounted for by the appearance of lactate in the incubation medium. The enzyme hexokinase my be involved in regulating this aerobic glycolysis. There is cosiderable indirect evidence for the utilisation of endogenous as opposed to exogenous energy substrates, the most likely candidate being protein. Information on early human embryo metabolismis likely to find application in a number of areas: these include the improvement of techniques for assisted human conception, notably in the selection of embryos for transfer following In Vitro Fertilisation; the diagnosis of gentic defects at the preimplantation stage; increased undersding of the causes of implantation failure and miscarriage, and the development of novel post‐coital contraceptives.