bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell Degeneration in the Larval Ventral Horn of Xenopus laevis (Daudin)
Authors: Hughes Arthur 
Published: April 2021

ABSTRACT
Cell death accompanies a variety of developmental processes in many tissues and systems of organs. A comprehensive review by Glücksmann (1951) has revealed how widespread is the occurrence of degenerating cells in vertebrate embryos. Within the developing nervous system, the earliest descriptions of cellular degeneration are due to Barbieri (1905) in Amphibia, and to Collin (1906) in the chick embryo. Since that time, destruction of cells has been observed in the morphogenesis of the neural tube, most recently by Boyd (1955) and by Kallen (1955) in early mammalian embryos; in the establishment of regional differences between limb and non limb-levels in spinal ganglia of the chick (Hamburger & Levi-Montalcini, 1949), and also in the histogenesis of Anuran ventral horn cells (Xenopus,Hughes & Tschumi, 1958; Eleutherodactylus,Hughes, 1959).
Systemic Influence on Activity of Hair Follicles in Skin Homografts
Authors: Ebling F. J. , Johnson Elizabeth 
Published: April 2021

ABSTRACTStrips of skin from the flank were exchanged between rats aged 28 and 49 days respectively, so that their expected hair growth waves would be out of phase. Similarly sited autografts were used as controls. In the wave of growth immediately following grafting eruption of hairs on the homografts coincided with that on the donor’s autograft. In the older recipient this was significantly in advance and in the younger recipient significantly in retard of hair growth on their autografts. Thus, follicular activity has an inherent rhythm which continues for at least one cycle after homotopic grafting. In the succeeding waves of growth, when follicular activity in the recipient preceded that in the donor, the time of eruption of hair on the homograft was advanced, and by the third wave after grafting was completely in line with its host. When follicular activity in the recipient succeeded that in the donor the homografts tended to behave donor-wise. These results show clearly that both an inherent rhythm and a systemic stimulus are involved in follicular activity at a particular site.
Certain Aspects of Cell Lineage and Morphogenesis Studied in Embryos of Drosophila melanogaster with an Ultra-violet Micro-beam
Authors: Hathaway D. S. , Selman G. G. 
Published: April 2021

ABSTRACT
A method is described for using a reflecting microscope to irradiate small precisely located areas of insect embryos with lethal micro-beams of ultraviolet light, so that cell lineages may be traced from histological studies of subsequent development. The gamete precursors in Drosophila melanogaster were shown to be those pole cells which are carried into the posterior mid-gut rudiment during gastrulation. The interblastodermal-migrating pole cells are not incorporated into the embryonic gonad but probably play a role in the formation of mid-gut epithelium. The mesodermal rudiment of the gonad is derived from the posterior half of the mid-ventral mesodermal invagination, and is formed independently of precursor gamete cells. Bilaterally and unilaterally castrated flies resulted after pole-cell irradiation. Support for certain parts of Poulson’s anlagen plan of the Drosophila egg was obtained from studies of development after irradiation of certain areas of blastema and blastoderm. The non-cellular blastema stage was more easily damaged by ultra-violet radiation than the blastoderm stage. Gastrulation was a critical stage, but the study supported Sonnenblick’s ideas concerning the morphogenic factors governing endodermal invagination. No departure from mosaicism was noticed, except that the results indicated some slight regulative capacity in the presumptive pole-cell area at the 1-hour stage.
Integrative genomic analysis of blood pressure and related phenotypes in rats
Authors: Takeuchi Fumihiko , Liang Yi-Qiang , Isono Masato , Tajima Michiko , Cui Zong Hu , Iizuka Yoko , Gotoda Takanari , Nabika Toru , Kato Norihiro 
Published: April 2021

ABSTRACT
Despite remarkable progress made in human genome-wide association studies, there remains a substantial gap between statistical evidence for genetic associations and functional comprehension of the underlying mechanisms governing these associations. As a means of bridging this gap, we performed genomic analysis of blood pressure (BP) and related phenotypes in spontaneously hypertensive rats (SHR) and their substrain, stroke-prone SHR (SHRSP), both of which are unique genetic models of severe hypertension and cardiovascular complications. By integrating whole-genome sequencing, transcriptome profiling, genome-wide linkage scans (maximum n=1415), fine congenic mapping (maximum n=8704), pharmacological intervention and comparative analysis with transcriptome-wide association study (TWAS) datasets, we searched causal genes and causal pathways for the tested traits. The overall results validated the polygenic architecture of elevated BP compared with a non-hypertensive control strain, Wistar Kyoto rats (WKY); e.g. inter-strain BP differences between SHRSP and WKY could be largely explained by an aggregate of BP changes in seven SHRSP-derived consomic strains. We identified 26 potential target genes, including rat homologs of human TWAS loci, for the tested traits. In this study, we re-discovered 18 genes that had previously been determined to contribute to hypertension or cardiovascular phenotypes. Notably, five of these genes belong to the kallikrein–kinin/renin–angiotensin systems (KKS/RAS), in which the most prominent differential expression between hypertensive and non-hypertensive alleles could be detected in rat Klk1 paralogs. In combination with a pharmacological intervention, we provide in vivo experimental evidence supporting the presence of key disease pathways, such as KKS/RAS, in a rat polygenic hypertension model.
The liver metastatic niche: modelling the extracellular matrix in metastasis
Authors: Drew James , Machesky Laura M. 
Published: April 2021

ABSTRACT
Dissemination of malignant cells from primary tumours to metastatic sites is a key step in cancer progression. Disseminated tumour cells preferentially settle in specific target organs, and the success of such metastases depends on dynamic interactions between cancer cells and the microenvironments they encounter at secondary sites. Two emerging concepts concerning the biology of metastasis are that organ-specific microenvironments influence the fate of disseminated cancer cells, and that cancer cell-extracellular matrix interactions have important roles at all stages of the metastatic cascade. The extracellular matrix is the complex and dynamic non-cellular component of tissues that provides a physical scaffold and conveys essential adhesive and paracrine signals for a tissue's function. Here, we focus on how extracellular matrix dynamics contribute to liver metastases – a common and deadly event. We discuss how matrix components of the healthy and premetastatic liver support early seeding of disseminated cancer cells, and how the matrix derived from both cancer and liver contributes to the changes in niche composition as metastasis progresses. We also highlight the technical developments that are providing new insights into the stochastic, dynamic and multifaceted roles of the liver extracellular matrix in permitting and sustaining metastasis. An understanding of the contribution of the extracellular matrix to different stages of metastasis may well pave the way to targeted and effective therapies against metastatic disease.
Synergic effect of atorvastatin and ambrisentan on sinusoidal and hemodynamic alterations in a rat model of NASH
Authors: Bravo Miren , Raurell Imma , Barberá Aurora , Hide Diana , Gil Mar , Estrella Federico , Salcedo María Teresa , Augustin Salvador , Genescà Joan , Martell María 
Published: April 2021

ABSTRACT
In non-alcoholic steatohepatitis (NASH), decreased nitric oxide and increased endothelin-1 (ET-1, also known as EDN1) released by sinusoidal endothelial cells (LSEC) induce hepatic stellate cell (HSC) contraction and contribute to portal hypertension (PH). Statins improve LSEC function, and ambrisentan is a selective endothelin-receptor-A antagonist. We aimed to analyse the combined effects of atorvastatin and ambrisentan on liver histopathology and hemodynamics, together with assessing the underlying mechanism in a rat NASH model. Diet-induced NASH rats were treated with atorvastatin (10 mg/kg/day), ambrisentan (30 mg/kg/day or 2 mg/kg/day) or a combination of both for 2 weeks. Hemodynamic parameters were registered and liver histology and serum biochemical determinations analysed. Expression of proteins were studied by immunoblotting. Conditioned media experiments were performed with LSEC. HSCs were characterized by RT-PCR, and a collagen lattice contraction assay was performed. Atorvastatin and ambrisentan act synergistically in combination to completely normalize liver hemodynamics and reverse histological NASH by 75%. Atorvastatin reversed the sinusoidal contractile phenotype, thus improving endothelial function, whereas ambrisentan prevented the contractile response in HSCs by blocking ET-1 response. Additionally, ambrisentan also increased eNOS (also known as Nos3) phosphorylation levels in LSEC, via facilitating the stimulation of endothelin-receptor-B in these cells. Furthermore, the serum alanine aminotransferase of the combined treatment group decreased to normal levels, and this group exhibited a restoration of the HSC quiescent phenotype. The combination of atorvastatin and ambrisentan remarkably improves liver histology and PH in a diet-induced NASH model. By recovering LSEC function, together with inhibiting the activation and contraction of HSC, this combined treatment may be an effective treatment for NASH patients.
Regulation of mitosis: III. cytological effects of 2,4,5-trichloro-phenoxyacetic acid and of dioxin contaminants in 2,4,5-T formulations
Authors: Jackson W. T. 
Published: April 2021

ABSTRACT
The conclusion of earlier studies that the pronounced cytological effects of 2,4,5-trichloro-phenoxyacetic acid (2,4,5-T) formulations are actually due to 2,4,5-T is unwarranted. Inhibition of mitosis and the development of cytological abnormalities are caused by a contaminant, 2&gt;3,7&gt;S-tetrachlorodibenzo-/&gt;-dioxin. The appearance and behaviour of dividing endosperm cells of the African blood lily (Haemanthus katherinae Baker) subjected to a 10−4 M solution of highly purified 2,4,5-T, observed in vitro by phase-contrast microscopy for a 2-h treatment period, did not differ significantly from controls. Subjecting these cells to 0·2 or 10μg/l. dioxin, to 0 2 μg/1. dioxin plus 10−4 M 2,4,5-T (highly purified sample), or to 10−1 M 2,4,5-T containing dioxin as a contaminant caused a dramatic inhibition of mitosis. These preparations also induced formation of dicentric bridges, chromatin fusion with formation of multinuclei or a single large nucleus. Impairment of the functioning of the mitotic apparatus was evident; chromosomes ‘floated free ‘in the cytoplasm. Both quantitative and qualitative data substantiate these conclusions.
In view of the extreme toxicity of dioxins to man, of their demonstrated teratogenic effects in some animals under experimental conditions, of their effectiveness in producing cytological effects in dividing cells formerly ascribed to 2,4,5-T, of their presence as contaminants in 2.4.5-T, pentachlorophenol, and other polychlorophenols, and of the potential for widespread contamination of the environment with dioxins, investigation of all facets of this class of compounds should be given high priority. It is quite possible that contamination of the environment with dioxins from sources of polychlorophenols is far greater than that contributed by 2.4.5-T. Amplification of dioxin levels in food chains is, of course, of particular concern.
Cell electrophoresis of the cellular slime mould Dictyostelium Discoideum: I. characterization of some of the cell surface ionogenic groups
Authors: Lee K.-C. 
Published: April 2021

ABSTRACT
The reduction in cell surface charge density during the early stages of differentiation of the cellular slime mould, Dictyostelium discoideum, has been studied by the technique of cell electrophoresis. Using specific chemical reagents, it was shown that the cell surface negative charge was probably due to side chain carboxyl groups of proteins. During differentiation, there was a decrease in the density of these groups, accompanied by an increase in that of amino groups. The significance of this finding is discussed in relation to cell surface structure and cell differentiation.
Dna synthesis in purified populations of avian erythroid cells
Authors: Williams A. F. 
Published: April 2021

ABSTRACT
By the use of equilibrium density-gradient centrifugation erythroblasts and early polychromatic erythrocytes have been isolated from avian anaemic bone marrow. Cells from both the unfractionated and purified preparations have been characterized in terms of their histological type, size, haemoglobin content and ability to synthesize DNA. Erythroblasts were the only cells to synthesize DNA and it appeared that their progeny, the polychromatic erythrocyte, failed to enter a new S’ phase. The experimental system described allows biochemical characterization of earlier stages of avian erythropoiesis than has previously been possible.
Pronuclear membrane alterations during approximation of pronuclei and initiation of cleavage in the rabbit
Authors: Gondos B. , Bhiraleus P. , Conner L. A. 
Published: April 2021

ABSTRACT
As the male and female pronuclei of flushed rabbit tubal ova approach each other, numerous projections appear on the proximal surfaces, resulting in a severely irregular appearance. Each pronuclear envelope consists of 2 parallel membranes separated by a distance of 40–60 nm; annular ‘pores ‘are conspicuous in regions of pronuclear approximation. Stacks of smoothsurfaced membranes form parallel annulate lamellae in the cytoplasm adjacent to the pronuclei. When the 2 pronuclei come to lie in direct apposition, the adjacent envelopes are flattened against one another, crowding out intervening cytoplasm and producing an arrangement of 4 equidistant membranes. Interspersed between segments of apposing membranes are small ‘cytoplasmic islets ‘. At several points along the approximating surfaces intemuclear channels form between adjacent projections. This results in partial pronuclear union, but not complete fusion. After disruption of the pronuclei and the appearance of chromosomal aggregates in the centre of the egg, segments of pronuclear membranes are still visible in the cytoplasm. The membrane fragments are associated with collections of smooth vesicles, the latter increasing greatly in number during cleavage.
Distribution of the intermediate elements operating in ER to Golgi transport
Authors: Saraste Jaakko , Svensson Kerstin 
Published: April 2021

ABSTRACT
We have used a 58 kDa membrane protein (p58) as a marker to study the transport pathway between the rough endoplasmic reticulum (ER) and the Golgi apparatus. Immunolocalization of p58 in fibroblasts showed its presence in a single cisterna and in small tubular and vesicular elements at the cis side of the Golgi apparatus. In addition, the protein was detected in large (200–500 nm in diameter) tubulovesicular structures, clustered in the Golgi region but also found in peripheral locations. These represent intermediates in ER to Golgi transport since they contained newly synthesized viral glycoproteins, arrested in cells at I5°C. The peripheral structures accumulated at low temperature but reclustered rapidly to the Golgi region upon shift of cells back to 37°C. This movement involved long intracellular distances and was efficiently inhibited by nocodazole, indicating that it requires the integrity of microtubules. In contrast, reclustering was unaffected by brefeldin A (BFA), suggesting that this compound affects ER to Golgi transport prior to the temperature-sensitive step. In BFA-treated cells p58 was localized to scattered, tubular, smooth ER clusters, found in close association with rough ER cisternae. The cellular distribution of the intermediate elements indicates that the sites of protein exit are widely distributed within the rough ER network. We suggest that the smooth ER locations where p58 accumulates in BFA-treated cells could represent such peripheral exit sites.
Reorganization of cytoplasmic structures during cell fusion
Authors: Zheng Qiang , Chang Donald C. 
Published: April 2021

ABSTRACT
In order to provide a better understanding of the dynamic process of cell fusion, we studied the reorganization of cytoplasmic structures in electrofused CV-1 cells. Using fluorescence microscopy and double staining methods, we examined correlations between the structural patterns of the major cytoskeletal proteins (microtubules, actin and vimentin intermediate filaments) and the distribution of various organelles (endoplasmic reticulum, mitochondria and nuclei) at different stages of cell fusion. Our results suggest that microtubules appear to play a primary role in the process of cytoplasmic reorganization. At the early stage of cell fusion, microtubules were observed to infiltrate rapidly into the newly formed cytoplasmic bridges and establish a connec tion between the cytoskeletal networks of fusing cells. The reorganization of microtubules was found to be correlated with the redistribution of endoplasmic reticulum (ER), vimentin intermediate filaments, mitochondria, and the aggregation of nuclei. The Factin system, on the other hand, appeared to be independent of the reorganization of the other cytoplasmic structures. The principal function of Factin during cell fusion is probably to widen the cytoplasmic bridges by lamellipodial extension.
Induction of vacuolar apical compartments in the Caco-2 intestinal epithelial cell line
Authors: Gilbert Thierry , Rodriguez-Boulan Enrique 
Published: April 2021

ABSTRACT
Complete disruption of the microtubular network by colchicine or nocodazole in Caco-2 intestinal epithelial cells results in the appearance of basolateral microvilli and brush border-containing intracellular vacuoles (vacuolar apical compartment: VAC). These vacuoles are surrounded by a terminal web, express apical markers and exclude basolateral markers. The vacuoles do not originate from internalized apical or basolateral plasma membrane and their development is blocked by protein synthesis inhibitors, suggesting that they are newly synthesized. After removal of the microtubule inhibitors, VACs are usually degraded and/or released into the lateral intercellular space. Rarely was fusion with the apical membrane observed. These experiments support a role for microtubules in the biogenesis of the apical surface and indicate that, under some conditions, apical plasma membrane assembly may occur in the cytoplasm, as observed in some human pathological states.
Characterization of luminal and basal cells flow-sorted from the adult rat mammary parenchyma
Authors: Dundas S. R. , Ormerod M. G. , Gusterson B. A. , O’hare M. J. 
Published: April 2021

ABSTRACT
Differentially expressed membrane antigens have been used to flow-sort viable luminal epithelial and myoepithelial cells from freshly disaggregated adult virgin rat mammary parenchyma. Resulting cultures and clones have been characterized morphologically and by a panel of antibodies that recognise cell-type-specific cytoskeletal antigens in the intact mammary gland. Five clonal phenotypes were recognisable by morphological criteria, three (types 1-3) exclusively associated with sorted luminal epithelial (25.5-positive) cells, and two (types 4 and 5) generated from the sorted myoepithelial (CALLA/neutral endopeptidase 24.11-positive) cells. All clones derived from myoepithelial cells continued to express a basal parenchymal marker in the form of the rat equivalent of human cytokeratin 14, while smooth muscle a-actin was expressed by the small slowly growing type 4 clones but was found in fewer cells in rapidly proliferating type 5 myoepithelially derived clones. Two of the luminal clone types, characterized by an attenuated appearance and slow growth (types 1/2), expressed only luminal-specific markers, including the equivalent of human cytokeratins 7/18/19. Type 3 clones, by contrast, consisted of rapidly proliferating cells, many of which either co-expressed CK14 and CK18 antigens (type 3a) or were composed of a mosaic of CK14+/CK18−, CK14+/CK18+ and CKI4−/ CK18+ cells (type 3b). The sorted myoepithelially derived clones grew faster than clones from sorted luminal cells as evidenced by the larger fraction of cells synthesizing DNA. All types of clone could be obtained from both isolated ducts and alveoli, when these were cloned separately, although there were some differences in their relative frequency. These results demonstrate a heterogeneity within both the luminal and the myoepithelial/basal compartments of the rat mammary parenchyma and provide the basis for studies of growth and differentiation of specific rodent mammary sub-populations in culture, and in vivo after transplantation.
Dictyostelium discoideumcontains two profilin isoforms that differ in structure and fuction
Authors: Haugwitz Michael , Noegel Angelika A. , Rieger Daniela , Lottspeich Friedrich , Schleicher Michael 
Published: April 2021

ABSTRACTTwo profilin isoforms (profilins I and II) have been purified from Dictyostelium discoideum, using affinity chromatography on a poly(L-proline) matrix; the isoforms could be separated by cation-exchange chromatography on a FPLC system. The gene coding for profilin I was cloned from a Agtll cDNA library using a profilin I-specific monoclonal antibody. The profilin II cDNA was isolated by probing the cDNA library with an oligonucleotide deduced from the N-terminal amino acid sequence of profilin II, which has an open N terminus in contrast to profilin I. The deduced amino acid sequences of both genes show that profilin I in comparison to profilin II is slightly larger (13 064 Da vs 12 729 Da), has a more acidic isoelectric point (calc, pl 6.62 vs 7.26) and shares with profilin II 68 identical residues out of 126 amino acids. Although both profilins contain a conserved lysine residue in the putative actin-binding region and can be crosslinked covalently to G-actin, the crosslinking efficiency of profilin II to actin is substantially higher than that of profilin I. These data are in agreement with studies on the functional properties of the profilin isoforms. In most prep arations profilin II was more efficient in delaying the onset of elongation during the course of actin polymerization and caused a higher critical concentration for actin polymerization than profilin I, probably due to the slightly increased affinity of profilin II for D. discoideum G-actin (approx. Kd l.8×10-6M) as compared to that of profilin I (approx. Kd 5.l× 10-6M). This difference was not always so obvious and, we are trying to identify non-protein-aceous co-purifying inhibitors that can obscure the data obtained from in vitro assays. The messenger RNA of both profilin isoforms is present throughout development of D. discoideum. However, whereas the profilin I-specific mRNA accumulates after 6-9 h of starvation (aggregation stage), the profilin II-specific mRNA peaks at early stages and disappears during later development almost completely. This suggests differential functions for the profilin isoforms during D. discoideum development.