bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trichostatin A and trapoxin: Novel chemical probes for the role of histone acetylation in chromatin structure and function
Authors: Yoshida Minoru , Horinouchi Sueharu , Beppu Teruhiko 
Published: February 2005

AbstractReversible acetylation at the ϵ‐amino group of lysines located at the conserved domain of core histones is supposed to play an important role in the regulation of chromatin structure and its transcriptional activity. One promising strategy for analyzing the precise function of histone acetylation is to block the activities of acetylating or deacetylating enzymes by specific inhibitors. Recently, two microbial metabolites, trichostatin A and trapoxin, were found to be potent inhibitors of histone deacetylases. Trichostatin A reversibly inhibits the mammalian histone deacetylase, whereas trapoxin causes inhibition through irreversible binding to the enzyme. The histone deacetylase from a trichostatin A‐resistant cell line is resistant to trichostatin A, indicating that the enzyme is the primary target. Both of the agents induce a variety of biological responses of cells such as induction of differentiation and cell cycle arrest. Trichostatin A and trapoxin are useful in analyzing the role of histone acetylation in chromatin structure and function as well as in determining the genes whose activities are regulated by histone acetylation.
Tumour suppressors, kinases and clamps: How p53 regulates the cell cycle in response to DNA damage
Authors: Cox Lynne S. , Lane David P. 
Published: February 2005

AbstractThe human tumour suppressor protein p53 is critical for regulation of the cell cycle on genotoxic insult. When DNA is damaged by radiation, chemicals or viral infection, cells respond rapidly by arresting the cell cycle. A G1 arrest requires the activity of wild‐type p53, as it is not observed in cells lacking functionally wild‐type protein, and at least some component of S phase and G2/M arrests is also thought to be p53‐dependent. p53 functions as a transcription factor which binds specific DNA sequences, and recently major downstream targets have been identified, including p21Cip1 an inhibitor of the cell cycle kinases that also blocks the replicative but not the repair function of DNA polymerase δ auxiliary factor, PCNA. Current interest focuses on developing novel cancer therapies based on our knowledge of the activity of p53 and p21Cip1 in the cell cycle.
Frontier questions about sister chromatid separation in anaphase
Authors: Yanagida Mitsuhiro 
Published: February 2005

AbstractSister chromatid separation in anaphase is an important event in the cell's transmission of genetic information to a descendent. It has been investigated from different aspects: cell cycle regulation, spindle and chromosome dynamics within the three‐dimensional cell architecture, transmission fidelity control and cellular signaling. Integrated studies directed toward unified understanding are possible using multidisciplinary methods with model organisms. Ubiquitin‐dependent proteolysis, protein dephosphorylation, an unknown function by the TPR repeat proteins, chromosome transport by microtubule‐based motors and DNA topological change by DNA topoisomerase II are all necessary for progression from metaphase to anaphase. Chromosome condensation, mitotic kinetochore function and spindle formation require a large number of proteins, which are prerequisites for successful sister chromatid separation. Factors that help to retain sister chromatid connection after replication and prevent premature separation remain to be determined. Although sister chromatid separation occurs in anaphase, gene functions in other cell cycle stages also ensure the progression of correct chromatid separation.
Drosophila development pulls the strings of the cell cycle
Authors: Reed Bruce H. 
Published: February 2005

AbstractThe three cycles of cell division immediately following theformation of the cellular blastoderm during Drosophila embryogenesis display an invariant pattern(1,2). Bursts of transcription of a gene called string are required and sufficient to trigger mitosis at this time during development(3). The activator of mitosis encoded by the string gene is a positive regulator of cdc2 kinase and a Drosophila homologue of the Saccharomyces pombe cdc25 tyrosine phosphatase(4,5). Evidence presented in a recent paper(6) demonstrates that transcription of string, and hence the timing and pattern of mitosis in the postblastoderm embryo, is under complex developmental control. Several lines of evidence support this interpretation, including the analysis of string transcription in pattern formation mutants, cell cycle arrest mutants, and the preliminary characterization of an extensive cis‐acting regulatory region.
Modulation of AP‐1/ATF transcription factor activity by the adenovirus‐e1a oncogene products
Authors: Hagmeyer Bertine M. , Angel Peter , van Dam Hans 
Published: February 2005

AbstractThe proteins encoded by early region 1 A (E1A) of human adenoviruses (Ad) modulate the expression of both adenovirus genes and various host cell genes. With these transcription‐regulating properties the E1A proteins redirect the cell's metabolism, which enables them to induce oncogenic transformation in rodent cells. The E1A proteins modulate transcription by interacting both with gene‐specific and general cellular transcription factors. Various members of the AP‐1 and ATF/CREB families of transcription factors are targets for E1A‐dependent regulation, including cJun, the protein product of the c‐jun proto‐oncogene. The E1A proteins modulate cJun‐dependent transcription both positively and negatively, and affect the activity as well as the expression levels of cJun. By increasing the phosphorylation status of cJun, E1A can stimulate transcription regulated by cJun/ATF2 heterodimers. In contrast, E1A inhibits the expression of various metalloproteases by interfering with the DNA‐binding capacity of cJun/cJun and cJun/cFos dimers, which might involve the association of E1A with the putative transcriptional coactivator p300. Since the ability of E1A to alter cJun‐dependent transcription correlates with its transforming capacity, interference with cJundependent transcription may be an essential step in E1A‐induced transformation.
UV‐induced skin cancer in a hairless mouse model
Authors: de Gruijl Frank R. , Forbes P. Donald 
Published: February 2005

AbstractUltraviolet (UV) radiation is a very common carcinogen in our environment, but epidemiological data on the relationship between skin cancers and ambient solar UV radiation are very restricted. In hairless mice the process of UV carcinogenesis can be studied in depth. Experiments with this animal model have yielded quantitative data on how tumor development depends on dose, time and wavelength of the UV radiation. In combination with epidemiological data, these experimental results can be transposed to humans. Comparative studies on molecular, cellular and physiological changes in mouse and man can further our fundamental understanding of UV carcinogenesis in man. This is likely to improve risk assessments such as those related to a stratospheric ozone depletion, and to yield well‐targeted intervention schemes, e.g. prescribing a specific drug or diet, for high‐risk individuals.
Is there a unique form of chromatin at the Saccharomyces cerevisiae centromeres?
Authors: Basrai Munira A. , Hieter Philip 
Published: February 2005

AbstractChromosome transmission in S. cerevisiae requires the activities of many structural and regulatory proteins required for the replication, repair, recombination and segregation of chromosomal DNA, and co‐ordination of the chromosome cycle with progression through the cell cycle. An important structural domain on each chromosome is the kinetochore (centromere DNA and associated proteins), which provides the site of attachment of chromosomes to the spindle microtubules. Stoler et al.(1) have recently reported the cloning of an essential gene CSE4, mutations in which cause chromosome nondisjunction of a marked chromosome bearing a centromere DNA mutation. The cse4–1 mutation causes cells to arrest in the G2/M phase of the cell cycle with a 2N DNA content in a RAD9 checkpoint‐independent manner. The carboxyl terminus of Cse4p and the human centromere‐localized protein CENP‐A have a high degree of homology to the C‐terminal domain of histone H3. Since both CENP‐A and Cse4p also have biochemical properties similar to histones H3 and H4, it is tempting to speculate that these histone H3‐like proteins are components of specialized nucleosomes, a class of which may be unique to the centromeres.
The SMC proteins and the coming of age of the chromosome scaffold hypothesis
Authors: Saitoh Noriko , Goldberg Iiya , Earnshaw William C. 
Published: February 2005

AbstractThe mechanism of chromosome condensation is one of the classic mysteries of mitosis. A number of years ago, it was suggested that nonhistone proteins of the chromosome scaffold fraction might help chromosomes to condense, possibly by constructing a framework for the condensed structure. Recent results have shown that topoisomerase II and the SMC proteins, two abundant members of the scaffold fraction, are required for chromosome condensation and segregation during mitosis. Topoisomerase II is a well‐characterized enzyme. In contrast, nothing is yet known about the function of the SMC proteins. We summarize evidence suggesting that these proteins may be enzymes whose activity is somehow involved in the establishment and maintenance of mitotic chromosome morphology.
Epidermal growth factor receptor function in early mammalian development
Authors: Wiley Lynn M. , Adamson Eileen D. , Tsark Eleanor C. 
Published: February 2005

AbstractWe review here the data indicating a role for epidermal growth factor receptor (EGF receptor) signalling in early mouse development. Embryonic development of the metazoan embryo generally begins with the formation of a cystic structure and epithelial layers that subsequently form anlagen of the definitive body parts and organs. For the mammalian embryo, this cystic structure is a blastocyst whose wall consists of trophectoderm, the first epithelium to develop during mammalian embryogenesis. The onset of expression and function of EGF receptors is coincident with the onset of trophectoderm development. Modulating EGF receptor expression and function modulates trophectoderm differentiation, leading to the hypothesis that functional EGF receptors participate in the induction of trophectoderm development and perhaps of other embryonic epithelial derivatives such as nervous tissues.
Two ways to skin a plant: The analysis of root and shoot epidermal development in Arabidopsis
Authors: Dolan Liam , Roberts Keith 
Published: February 2005

AbstractThe post‐embryonic architecture of higher plants is derived from the activity of two meristems that are formed in the embryo: the shoot meristem and the root meristem. The epidermis of the shoot is derived from the outermost layer of cells covering the shoot meristem through repeated anticlinal divisions. By contrast, the epidermis of the root is derived from an internal ring of cells, located at the centre of the root meristem, by a precise series of both periclinal and anticlinal divisions. Each epidermis has an independent origin. In Arabidopsis the mature shoot epidermis is composed of a small number of cell types: hair cells (trichomes), stomatal guard cells and other epidermal cells. In shoots, hairs take the form of branched trichomes that are surrounded at their base by a ring of accessory cells in a sheet of epidermal cells. The root epidermis is composed of two cell types: trichoblasts that form root hair cells and atrichoblasts that form non‐hair cells. Mutations affecting both the patterning and the morphogenesis of cells in both shoot and root epidermis have recently been described. Most of these mutations affect development in a single epidermis, but at least one, ttg, is involved in development in both epidermal systems.
Life and death by P53
Authors: Elledge Richard M. , Lee Wen‐Hwa 
Published: February 2005

Abstractp53 is a multifunctional protein which plays a role in modulating gene transcription, policing cell cycle checkpoints, activating apoptosis, controlling DNA replication and repair, maintaining genomic stability and responding to genetic insults. Mutation of the p53 gene confers the single greatest known selective advantage favoring cancer formation. Point mutations result not only in the loss of tumor suppressor functions, but also in the gain of tumor promotion functions. These dual circumstances may be unique to p53 and, in part, could explain the relatively powerful force behind this selection pressure. General mechanisms of gain of function by mutated p53 may include alteration in transcriptional modulation and newly acquired targets for transcriptional regulation and protein binding. Despite the direct significance of p53 mutations, loss of the remaining wild‐type allele is usually required for the formation of tumors in the natural setting. Novel applications of the basic scientific knowledge of p53 could lead to an improvement in cancer treatment, hopefully in the not so distant future.
A fragile gene
Authors: Oostra Ben A. , Willems Patrick J. 
Published: February 2005

AbstractFragile X syndrome is the most common cause of inherited mental retardation in humans. The fragile X gene (FMR1) has been cloned and the mutation causing the disease is known. The molecular basis of the disease is an expansion of a trinucleotide repeat sequence (CGG) present in the first exon within the 5′ untranslated region of the FMR1 gene. Affected individuals have repeat CGG sequences of above 200. As a result the gene is not producing protein. It has been shown that the FMR1 protein has RNA binding activity, but the function of this RNA binding activity is not known. The timing and mechanism of repeat amplification are not yet understood. An animal model for fragile X syndrome has been generated, which can be used to study the clinical and biochemical abnormalities caused by absence of FMR1 protein product.
Development, databases and the internet
Authors: B. L. Bard Jonathan , Davies Jamie A. 
Published: February 2005

AbstractThere is now a rapidly expanding population of interlinked developmental biology databases on the World Wide Web that can be readily accessed from a desk‐top PC using programs such as Netscape or Mosaic. These databases cover popular organisms (Arabidopsis, Caenorhabditis, Drosophila, zebrafish, mouse, etc.) and include gene and protein sequences, lists of mutants, information on resources and techniques, and teaching aids. More complex are databases relating domains of gene expression to embryonic anatomy and these range from existing text‐based systems for specific organs such as kidney, to a massive project under development, that will cover gene expression during the whole of mouse embryogenesis. In this brief article, we review selected examples of databases currently available, look forward to what will be available soon, and explain how to gain access to the World Wide Web.
Rubisco rules fall; gene transfer triumphs
Authors: Palmer Jeffrey D. 
Published: February 2005

AbstractThe most common form of the CO2‐fixing enzyme rubisco is a form I enzyme, heretofore found universally in oxygenic phototrophs (cyanobacteria and plastids) and widely in proteobacteria. Two groups(1–4), however, now report that in dinoflagellate plastids the usual form I rubisco has been replaced by the distantly related form II enzyme, known previously only from anaerobic proteobacteria. This raises the important question of how such an oxygensensitive rubisco could function in an aerobic organism. Moreover, the dinoflagellate rubisco has unusual molecular properties: it is encoded as a polyprotein, by nuclear (rather than plastid) genes, and these genes contain noncanonical spliceosomal introns. The nuclear location and alphaproteobacterial affinity of dinoflagellate rubisco genes hint at a possible mitochondrial origin and highlight the extraordinary richness of lateral gene transfers, both between and within organisms, that have occurred during rubisco evolution.
The chondrocyte, architect of cartilage. Biomechanics, structure, function and molecular biology of cartilage matrix macromolecules
Authors: Muir Helen 
Published: February 2005

AbstractChondrocytes are specialised cells which produce and maintain the extracellular matrix of cartilage, a tissue that is resilient and pliant. In vivo, it has to withstand very high compressive loads, and that is explicable in terms of the physico‐chemical properties of cartilage‐specific macromolecules and with the movement of water and ions within the matrix. The functions of the cartilage‐specific collagens, aggrecan (a hydrophilic proteoglycan) and hyaluronan are discussed within this context. The structures of cartilage collagens and proteoglycans and their genes are known and a number of informative mutations have been identified. In particular, collagen fibrillogenesis is a complex process which can be altered by mutations whose effects fit what is known about collagen molecular structural functions. In other instances, mutations have indicated new functions for particular molecular domains. As cartilage provides the template for the developing skeleton, mutations in genes for cartilage‐specific proteins often produce developmental abnormalities. The search for mutations amongst such genes in heritable disorders is being actively pursued by many groups, although mutation and phenotype are not always well correlated, probably because of compensatory mechanisms. The special nature of the chondrocyte is stressed in connection with its cell involvement in osteoarthritis, the most widespread disease of diarthrodial joints.
Gamete and immune cell recognition revisited
Authors: Belton Robert J. , Foltz Kathleen R. 
Published: February 2005

AbstractFertilization is the result of a series of successful recognition and binding events mediated by gamete surface molecules. Recent advances in the identification and characterization of some of these recognition molecules provide extremely valuable information necessary to understand sperm‐egg recognition and subsequent egg activation. We discuss these new data in the context of the model of gamete recognition first proposed by F.R. Lillie in the early part of the 20th century, and revisited periodically in the subsequent literature, which relates fortilization events to those of immune cell recognition and activation events. Here we discuss the principles underlying the molecular recognition and activation mechanisms of gametes and immune cells.
Activation of mammalian gene expression by the UV component of sunlight – from models to reality
Authors: Tyrrell Rex M. 
Published: February 2005

AbstractUltraviolet radiation activates the expression of a wide variety of genes, by pathways which differ between the short non‐solar ultraviolet C (UVC) wavelengths, which are strongly absorbed by nucleic acids, and the long solar ultraviolet A (UVA, 320–380 nm) wavelengths, which generate active oxygen intermediates. Intermediate solar ultraviolet (UV) wavelengths in the UVB (290–320 nm) range also contain an oxidative component, but more closely resemble UVC in their gene activating properties. Short wavelength UV, in common with other extracellular stimuli including growth factors, activates signal transduction events that involve both stress‐ and mitogen‐activated protein kinase cascades. The extrapolation of the complex modulation of gene expression that ensues to the consequences of natural UV exposure requires careful attention to the details of doses and wavelength employed in the model experiments. Nevertheless, there is evidence that UVB irrradiation of skin can activate the expression of proteins including immunomodulating cytokines, ornithine decarboxylase and, to a limited extent, nuclear oncogene products, as well as lead to stabilisation of p53. Non‐cytotoxic doses of UVA radiation also lead to the strong activation of several genes which would be expected to have functional relevance in vivo.
Moths: Myths and mysteries of stress resistance
Authors: Koval Thomas M. 
Published: February 2005

AbstractA cabbage looper's job, in many respects not unlike our own, is to survive its early developmental period and grow up healthy, metamorphose into an adult moth, and beget the next generation of loopers. Given its numerous predators, exposure to the continuous barrage of toxic physical, chemical and biological agents delivered by humans in an effort to eradicate it, as well as nature's own hazards, such as the ultraviolet component of sunlight and hazardous natural chemicals in plants that serve to deter ingestion by the looper, it is not difficult to view the looper as a highly stressed organism. However, the looper and its lepidopteran ancestors have been quite successful at resisting such hazards since the Mesozoic Era. The purpose of this brief review will be to examine some of the potential mechanisms by which the looper and its relatives have been able to be so successful over these past 200 million years.
Sequence‐dependent DNA structure
Authors: Hunter Christopher A. 
Published: February 2005

AbstractThe three‐dimensional structure of DNA depends subtly on its sequence, and this property is used by the proteins that regulate gene expression to locate their target sequences. Despite the large body of experimental data that has been accumulated on the relationship between sequence and DNA structure, we still do not fully understand the molecular basis for these properties, nor can we predict a three‐dimensional structure from a given sequence. We have been using computer modelling to tackle these problems. Some of our results and the implications for understanding the biological role of key sequences are discussed here.
Touch sensation in Caenorhabditis elegans
Authors: Herman Robert K. 
Published: February 2005

AbstractThe nematode C. elegans exhibits a variety of reponses to touch. When specific sets of mechanosensory neurons are killed with a laser, specific touch responses are abolished. Many mutations that result in defective mechanosensation have been identified. Some of the mutations define genes that specify the fate of a set of mechanoreceptors called the touch cells, which mediate response to light touch to the body of the worm. Genes specifying touch cell fate appear to regulate genes that encode touch‐cell differentiation proteins, including apparent subunits of a touch‐cell‐specific ion channel, rare mutant forms of which lead to swelling and lysis of the touch cells. Molecular attachments of the ion channel, both to extracellular matrix components and, intracellularly, to a special large‐diameter microtubule, may be required for mechanical gating of the channel. A mechanoreceptor‐interneuron‐motorneuron reflex circuit for response to light touch has been proposed.
Multiple growth factors are associated with lesions of atherosclerosis: Specificity or redundancy?
Authors: Raines Elaine W. , Ross Russell 
Published: February 2005

AbstractWithin the last five years, a number of specific growth factors have been localized in developing lesions of atherosclerosis. This localization of growth factors that is not observed in normal vessels, together with the pleotrophic activities of growth factors, have suggested a role for growth factors in atherosclerotic lesion progression. However, based on in vitro studies, many of the growth factors identified in lesions have overlapping target cells and are derived from the same cellular sources. What is the relative role of the specific growth factors identified? How is the their activity altered by the local conditions in the vessel wall? How do different risk factors for atherosclerosis alter the balance between growth factors and their natural regulators? Evidence for the involvement of specific growth factors in the progression of lesions of atherosclerosis is discussed, as well as the multiple levels at which the activities of these growth factors may be regulated by the vessel wall.