bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluidity of the Neural Epithelium During Forebrain Formation in Rat Embryos
Authors: Morriss-Kay Gillian , Tuckett Fiona 
Published: May 2013

ABSTRACT
During neurulation in rat embryos, the forebrain grows more rapidly than can be accounted for by intrinsic cell division alone, while the adjacent midbrain/rostral hindbrain maintains a constant cell number despite a high mitotic index (the cell cycle time is 6h throughout the neural epithelium). We have proposed that neuroepithelial cells flow in a rostral direction within the midbrain/rostral hindbrain region, towards and into the rapidly expanding forebrain. Evidence in support of this hypothesis is provided by cell-labelling studies: labelled neuroepithelial cells were injected into specific sites in the midbrain or rostral hindbrain neuroepithelium of unlabelled embryos ; after culture of these embryos for 24 h, the labelled cells were found in positions rostral to the injection sites.
In the midbrain/rostral hindbrain region, mitotic spindles were found to be predominantly orientated parallel with the long axis of the embryo; transversely orientated spindles were more frequently observed close to the lateral edges than more medially. Neural crest cells emigrate from the lateral edges during neurulation. These observations suggest that mitotic spindle orientation reflects the direction of cell movement: in the lateral region movement towards the lateral edge would maintain cell number in the transverse plane as neural crest cells emigrate; elsewhere, cells are moving mainly in the longitudinal plane, towards the forebrain. The possible causal relationship between cell movement and mitotic spindle orientation is discussed.
Cell flow within the intact neural epithelium is compared with cell flow in the intestinal villus epithelium. Other types of epithelial cell movement observed in the cranial neural epithelium during neurulation include expansion and shrinkage of the epithelial surface associated with change of cell shape and microfilament-mediated curvature. Cell rearrangement involving exchange of neighbours and cell movement towards and into a site of epithelio-mesenchymal conversion are also implicated.
A Unified Approach to Analysing Cell Motility
Authors: Dunn G. A. , Brown A. F. 
Published: May 2013

ABSTRACT
The quantitative analysis of cell motility in culture has several important functions. First, it gives a concise and accurate description of the motile process and can detect subtle differences in motility- due to different genetic makeup or experimental conditions. Second, its objectivity means that results can be communicated precisely and used unambiguously to test hypotheses about motility. Third, it may be used to derive a mathematical model with the same statistical properties as the motile process and thus elucidate the mechanism of motility.
In this paper, we introduce a general procedure for analysing cell motility in a wide variety of circumstances. We describe a pilot project for the analysis of simple geometrical data obtained from randomly moving fibroblasts. Finally, as an example, we show how an analysis of the translocation of the fibroblasts can lead to insights into the mechanism of motility that are arguably not obtainable by any other approach.
Cell Motility and the Problem of Anatomical Homeostasis
Authors: Harris Albert K. 
Published: May 2013

ABSTRACT
The locomotion of tissue cells need not be invasive or disrupt normal tissue geometry, as occurs in cancer. The normal relationship between anatomical structure and cell locomotion is exactly the reverse, with motility serving to create and maintain the structures of the body. This relationship is most extreme in sponges, where time-lapse films show that the cells move about continually in patterns that restructure these animals’ simple anatomy. The cells choose their position according to their differentiated cell type, which is the opposite of what is usually assumed to occur in development and has important implications for the functional significance of histotypic cell sorting.
A particular type of cellular force that seems to be important in morphogenesis is the traction that all motile tissue cells exert. This traction can be studied by culturing cells on very thin sheets of silicone rubber, so that the locations and variations in the cellular forces are made visible by the wrinkles they produce in the rubber substratum. One finding has been that the traction forces exerted by untransformed fibroblasts are very much stronger than is needed for their own locomotion, but are well adapted for the function of rearranging and aligning collagen fibres to form structures like ligaments, tendons and muscles. These forces are found to be greatly weakened by neoplastic transformation, however, suggesting that malignant invasiveness results from some sort of deflection of cell traction forces from their proper morphogenetic functions, so as to produce uncontrolled invasion.
To explain how motile cells create and maintain structures, as well as how their locomotion sometimes becomes perverted into the form of cancerous invasiveness, what seems to be needed is an extension of the concept of homeostasis to apply to the control of geometric relations between cells. This task may not be easy; one obstacle is the widespread belief that asymptotic stability implies the minimization of free energy. Instead, I suggest that stability results from balance of opposing forces within tissues, and that genes control which anatomical shapes will exist by determining the rules by which the relative strengths of these forces vary as functions of shape: to control shape, one must control the way forces vary with shape.
Recombinant retrovirus-mediated gene transfer to normal haemopoietic cells
Authors: Johnson G. R. 
Published: May 2013

ABSTRACT
Several of parameters seeking to increase the infection frequency of normal haemopoietic cells by recombinant retroviruses containing a drug selectable marker and/or a haemopoietic growth factor gene have been compared. By using bone marrow cells pretreated with 5-fluorouracil, cocultivation of cells for at least 4 days with virus producing fibroblasts, and addition of pokeweed mitogen stimulated spleen cell conditioned medium, from 30 to 100% of haemopoietic spleen colony forming cells (CFU-S) could be infected.
Because drug (G-418) selection was found to select subsets of CFU-S, a retrovirus lacking the drug selectable marker Neor, but containing a GM-CSF gene, was used to study the effects of endogenous GM-CSF production on CFU-S differentiation. Infected CFU-S produced equivalent numbers of erythroid and neutrophil-macrophage committed progenitor cells to control uninfected CFU-S. However, the progeny of infected CFU-S produced GM-CSF, some cells grew autonomously and neutrophil numbers were greatly increased at the expense of erythroblasts. These results suggest that unregulated GM-CSF production, although not altering commitment, alters the amplication phase following commitment.
The ras oncogenes
Authors: Marshall C. J. 
Published: May 2013

ABSTRACT
Oncogenic forms of the p21ras genes have been found in a large variety of human malignancies and tumours induced in animals by chemical carcinogens or irradiation. The active form of the p21 ras proteins is the GTP bound state and oncogenic mutations result in the protein being constitutively in the GTP bound active state. There is evidence to suggest that activating mutations can occur either as initiating steps in carcinogenesis or as later events in the evolution to frank neoplasia. To transduce a signal for proliferation and transformation the active GTP form of p21ras must interact with one or more cellular targets. Genetic experiments suggest that one potential effector molecule is the GTPase activating protein GAP. However, the mechanism by which interaction with GAP results in proliferation and transformation remains to be elucidated.
Mesenchymal influences on epithelial differentiation in developing systems
Authors: Sharpe P. M. , Ferguson M. W. J. 
Published: May 2013

ABSTRACT
Mesenchyme tissue: cells, matrix and soluble factors, influence the morphogenesis, proliferation and differentiation of a variety of embryonic epithelia, e.g. in the tooth, skin, mammary and salivary glands. Mesenchyme derivatives also ‘maintain’ adult epithelia, e.g. the local proliferation rate and cytokeratin composition of oral mucosa. Abnormalities in such epithelial-mesenchymal interactions lead to a variety of pathologies such as premalignant lesions, e.g. leukoplakia, tumours and psoriasis, whilst therapeutic manipulation of such interactions can prevent the exfoliation of dental implants. In all of these systems it is critical to understand, at the cellular and molecular levels, how the mesenchyme signals to the epithelium and how the latter processes and responds to such signals. We have investigated such questions using the developing embryonic palate both as a model system and as an important organ: failure of mesenchymal signalling leads to the common and distressing birth defect of cleft palate.
Bilateral palatal shelves arise from the maxillary processes of embryonic day 11 (Ell) mice, grow initially vertically down the sides of the tongue, elevate on E13-8 to a horizontal position above the dorsum of the tongue and fuse with each other in the midline on E14. The medial edge epithelia of each shelf fuse with each other to form a midline epithelial seam, suprabasal cells die, and the basal (stem) cells synthesize extracellular matrix molecules and turn into mesenchymal cells. Simultaneously the oral epithelia differentiate into stratified squamous cells and the nasal epithelia into pseudostratified ciliated columnar cells. Oral, medial and nasal epithelial differentiation is specified by the underlying mesenchyme in vivo and in vitro. Signalling involves a bifurcating action of a combination of soluble growth factors e.g. TGF-α, TGF-β, PDGF and FGF on palatal epithelia and mesenchyme. These factors stimulate the synthesis of specific extracellular matrix molecules by palate mesenchyme cells, and the appearance of receptors for such molecules on epithelial cells. In this way, a combination of mesenchymal soluble factors and extracellular matrix molecules direct palatal epithelial differentiation. These signals act on epithelial basal (stem) cells, causing them to synthesize unique proteins, which may direct subsequent differentiation of daughter cells. In the most extreme example, namely the medial edge epithelia, these signals result in the basal epithelial cells transforming into mesenchymal cells, thus demonstrating that they are indeed multipotential stem cells.
Stem cell renewal and differentiation in acute myeloblastic leukaemia
Authors: Mcculloch E. A. , Minden M. D. , Miyauchi J. , Kelleher C. A. , Wang C. 
Published: May 2013

ABSTRACT
The defining properties of stem cells are capacities for self-renewal and, after determination, a limited number of terminal divisions. The blast cells of acute myeloblastic leukaemia (AML) are maintained by stem cells with these two properties. Since renewal and differentiation can be assessed separately in cultures of AML blasts, these cancer cells provide a useful model for examining stem regulation; such studies have practical importance for future developments in the treatment of AML. This paper considers three aspects of blast cell biology. First, evidence is presented that self-renewal and differentiation are regulated by specific genes; further, the DNA encoding these genes has structural features that affect the chemosensitivity of self-renewal. This sensitivity varies from patient-to-patient and is an important attribute contributing to variation in treatment efficacy. Second, the effects of myelopoietic growth factors on blast stem cells are presented and discussed, as these bear on the regulation of the balance between renewal and differentiation. Finally, models of leukaemic haemopoiesis are considered in light of the experimental findings. The suggestion is advanced that leukaemia can be explained better by abnormalities of gene expression than by blocked differentiation.
Stem cells in mammary gland differentiation and cancer
Authors: Rudland Philip S. , Barraclough Roger 
Published: May 2013

ABSTRACT
Evidence based on ultrastructure and immunocytochemical staining suggests that morphological gradations between epithelial and myoepithelial cells, and possibly between epithelial and alveolar-like cells, can occur in terminal ductal structures of rat and human mammary glands. In neoplastic disease the benign, carcinogen-induced rat and benign, human mammary tumours can contain epithelial, myoepithelial-like and alveolar-like cells, whereas their malignant counterparts mainly contain only epithelial-like cells. Clonal epithelial cell lines from normal rat mammary glands, from benign tumours and from SV4O-transformed human mammary cultures can differentiate to either myoepithelial-like or alveolar-like cells. In those of the rat, the differentiation processes occur in steps, intermediate cells along the myoepithelial-like pathway resemble the morphological intermediates in the terminal ductal structures in vivo. Changes in specific polypeptides characterize each of the intermediate cells in vitro. One of the earliest increases observed in the myoepithelial-like pathway in vitro is that due to a novel protein p9Ka, whereas the major increases in Thy-1 antigen and the basement membrane proteins laminin and type IV collagen occur at later steps. The nucleotide sequence of the gene for p9Ka is related to that of the small, regulatory calcium-binding proteins, and antibodies raised to synthetic fragments of its predicted amino acid sequence react with only myoepithelial cells within the rat mammary parenchyma. Increases in the production of p9Ka and Thy-1 are largely due to increases in their messenger RNAs, possibly arising at the level of transcription of the DNA, whereas the increases in production of laminin and type IV collagen occur at a post-transcriptional level. The normal transcriptional promoter sequences of TATA or CAAT are not found adjacent to the genes for p9Ka or Thy-1. Cells and cell lines from malignant rat mammary tumours of increasing metastatic potential and from malignant areas of human ductal carcinomas largely fail to yield fully differentiated myoepithelial-like or alveolar-like cells in culture; however, weakly metastasizing rat cells yield variants which may retain a vestige of the myoepithelial phenotype. It is suggested that novel regulatory transcriptional element(s) may control the production of some of the proteins along the normal myoepithelial-like pathway, and that these elements may be relatively unique in their capacity to become inoperative in the malignant breast cancer cell.
Differentiation of fibroblast stem cells
Authors: Bayreuther Klaus , Rodemann H. Peter , Francz Pal. I. , Maier Katharina 
Published: May 2013

ABSTRACT
Primary human skin fibroblasts derived from the abdomen of 45 female donors of the four age groups 1–20, 20–40, 40–60, and 60–80 years were studied in primary explant, in primary low-density mass cultures, and in primary clonal populations in vitro. As a function of the age of the donor, primary mitotic and postmitotic fibroblasts in the three primary cell systems analysed represent heterogeneous populations with reproducible changes in the proportions of the mitotic fibroblasts MF I, MF II, MF III, and postmitotic fibroblasts PMF IV, PMF V, PMF VI, and PMF VII. These findings make it very likely that equivalent cell types exist in the connective tissue of skin in vivo, and that these cells undergo reproducible changes in the proportions of the mitotic and postmitotic counterparts in vivo as a function of the age of the donor. Secondary mitotic human skin fibroblast populations of the cell line HH-8 in vitro underwent 53-6 ± 6-0 cumulative population doublings (CPD) in 302 ± 27 days. If appropriate methods are applied, mitotic fibroblasts differentiate spontaneously into postmitotic fibroblasts which are kept in stationary cultures for up to 305 ± 41 additional days.(As a function of the CPD level and of the duration of stationary culture, secondary mitotic and postmitotic fibroblast populations are heterogeneous populations with reproducible changes in the proportions of mitotic fibroblasts MF I, MF II, and MF III, and postmitotic fibroblasts PMF IV, PMF V, PMF VI, and PMF VII. The seven secondary fibroblast cell types show differentiation-dependent and cell-type specific patterns of [35S]methionine polypeptides in total soluble cytoplasmic and nuclear proteins, in secreted proteins, and in membrane bound proteins. These findings make it very likely that the morphologically recognizable primary and secondary fibroblasts differentiate spontaneously along a seven stage terminal cell lineage MF I - MF II - MF III - PMF IV - PMF V - PMF VI - PMF VII in three compartments of the fibroblast stem cell system.
A novel C-terminal signal sequence targets Escherichia coli haemolysin directly to the medium
Authors: Gray Lindsay , Baker Karen , Kenny Brendan , Mackman Nigel , Haigh Richard , Holland I. Barry 
Published: May 2013

ABSTRACT
Escherichia coli haemolysin (HlyA), a 107K (K = 103Mr) protein, is secreted to the medium in an hlyB, hlyD-dependent process. Secretion, however, depends on neither an N-terminal signal sequence nor on SecA, which is part of the normal cellular export machinery for periplasmic and outer membrane proteins. In contrast, HlyA contains a novel C-terminal secretion signal encompassing the last 27 amino acids and possibly some additional residues immediately upstream. This region is characterized by a 16 residue ‘aspartic acid box’ composed largely of small amino acids which we propose constitutes an important element in recognition of the membrane translocation complex constituted by HlyB and HlyD. This feature is also found at the C-terminus of the adenyl cyclase and leukotoxin A molecules and resembles a recently identified eukaryotic C-terminal signal for targeting to glycosomes.
A domain of the HlyB component of the haemolysin transport system is also similar to a domain widely distributed in nature, apparently acting as an ATP-dependent transport protein for a wide variety of molecules. Secretion of haemolysin, however, is the first example of a protein translocation system involving an HlyB-like molecule. This suggests that a major role of HlyB or at least its C-terminal domain is the coupling of energy to translocation of the haemolysin. It is more likely therefore that HlyD is more involved in the actual translocation through the membrane.
On the basis of genetical and biochemical studies we propose that the haemolysin is translocated directly to the medium bypassing the periplasm. We further propose that HlyB and HlyD together constitute a membrane-bound translocator specific for molecules bearing the HlyA targeting sequence, and that the organization of this complex (conceivably involving other E. coli membrane proteins) must somehow straddle the inner and outer membranes.
Finally, the HlyA C-terminal domain has been successfully used to promote the secretion to the medium of a number of heterologous polypeptides, in an HlyB,D-dependent manner.
The use of gene-fusions to determine membrane protein topology in Saccharomyces cerevisiae
Authors: Green G. Neil , Hansen William , Walter Peter 
Published: May 2013

ABSTRACT
We have used protein-fusions to study in Saccharomyces cerevisiae the topology and integration of arginine permease. Since this membrane protein does not contain a cleavable signal sequence, we sought to identify the first internal signal by, initially, fusing the cytoplasmic enzyme, galactokinase, to various positions along the amino-terminal region, and then measuring in vitro the translocation of galactokinase across the membrane of the endoplasmic reticulum. Five fusion proteins were examined that contained, progressively, zero to four hydrophobic segments. The galactokinase moiety of fusion 5, but not fusions 1—4, was translocated. Fusion 4 differed from 5 by only the fourth hydrophobic segment, indicated that this region contains the first internal signal. From this we conclude that hydrophobic segment IV spans the membrane, and that the hydrophilic domain amino-terminal to it lies on the cytoplasmic side of the membrane. If any of the first three segments actually span the membrane, then they probably integrate by a mechanism that differs from segment IV.
Gene products required for chromosome separation
Authors: Yanagida Mitsuhiro 
Published: May 2013

ABSTRACT
Gene products required for mitotic chromosome separation in the .fission yeast Schizosaccharo- myces pombe are described. They have been identified by two distinct strategies of mutant isolation, followed by gene cloning and immunochemical characterization of gene products. The roles of four representative genes, namely nda3+, nuc2+, top2+ and dis2+, encoding β-tubulin, a nuclear scaffold-like protein, DNA topoisomerase II and type-1 protein phosphatase, respectively, are discussed in regard to the mechanisms and control of chromosome separation.
The mammalian cdc2 protein kinase: mechanisms of regulation during the cell cycle
Authors: Draetta Giulio , Beach David 
Published: May 2013

ABSTRACT
Recent experimental evidence has demonstrated the central role of the cdc2 protein kinase in the transition from G2 to M phase in eukaryotic cells. We shall review our knowledge of the mechanisms which coordinate activation of the kinase with cell cycle-specific events in mammalian cells.
The role of cyclin synthesis, modification and destruction in the control of cell division
Authors: Minshull Jeremy , Pines Jon , Golsteyn Roy , Standart Nancy , Mackie Shaun , Colman Alan , Blow Julian , Ruderman Joan V. , Wu Mike , Hunt Tim 
Published: May 2013

ABSTRACT
This paper reviews our current knowledge of the cyclins based on observations of the oocytes and eggs of sea urchins, clams and frogs. Cyclins are proteins found in all eukaryotes whose special property is rapid destruction at specific stages in the cell cycle. The cyclins fall into three families. A-type cyclins have been found in clams, flies and frogs. B-type cyclins have been found in clams, flies, frogs, sea urchins and fission yeast. A more distantly related family of three genes is found in Saccharomyces cerevisiae. B-type cyclins appear to be required for cells to enter mitosis, and their destruction is thought to be necessary for exit from mitosis. We describe evidence in support of these ideas, and describe various conditions under which cyclin destruction is delayed or deranged. We conclude with a discussion of the relationship between the cyclins and maturation- (or M phase-) promoting factor and some ideas on how the cyclins may work.
Nuclear envelope dynamics and nucleocytoplasmic transport
Authors: Stewart Murray , Whytock Sue , Moir Robert D. 
Published: May 2013

ABSTRACT
We have combined structural, biochemical and recombinant DNA methods to explore molecular interactions involved in nuclear envelope assembly dynamics and nucleocytoplasmic transport. Electron microscopy has established the overall architecture of the envelope and the relationship between nuclear pores, lamina fibres and pore-connecting fibrils. The lamin proteins that constitute the lamina resemble intermediate filament proteins, and assemble and disassemble during mitosis in response to phosphorylation. Lamins have been expressed in E. coli to facilitate structural investigations and the exploration of interaction sites with other envelope components. Disruption of envelopes has shown that nuclear pores are constructed from a central cylinder with cytoplasmic and nucleoplasmic rings. Examination of envelopes transporting gold-labelled nucleoplasmin has indicated that the transport pathway is complex and probably involves ring components in addition to the central cylinder. Molecular motors may be involved in changes in pore shape to enable transport and in the translocation mechanism.