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Transforming growth factor-beta induces loss of epithelial character and smooth muscle cell differentiation in epicardial cells.

During embryogenesis, epicardial cells undergo epithelial-mesenchymal transformation (EMT), invade the myocardium, and differentiate into components of the coronary vasculature, including smooth muscle cells. We tested the hypothesis that transforming growth factor-beta (TGFbeta) stimulates EMT and smooth muscle differentiation of epicardial cells. In epicardial explants, TGFbeta1 and TGFbeta2 induce loss of epithelial morphology, cytokeratin, and membrane-associated Zonula Occludens-1 and increase the smooth muscle markers calponin and caldesmon. Inhibition of activin receptor-like kinase (ALK) 5 blocks these effects, whereas constitutively active (ca) ALK5 increases cell invasion by 42%. Overexpression of Smad 3 did not mimic the effects of caALK5. Inhibition of p160 rho kinase or p38 MAP kinase prevented the loss of epithelial morphology in response to TGFbeta, whereas only inhibition of p160 rho kinase blocked TGFbeta-stimulated caldesmon expression. These data demonstrate that TGFbeta stimulates loss of epithelial character and smooth muscle differentiation in epicardial cells by means of a mechanism that requires ALK5 and p160 rho kinase.

Activin Receptors, Type I↗

Genetic regulation of multispecific antibody responsiveness: improvement of "high" and "low" characters.

The five selections carried out in the mouse for high or low antibody responsiveness to various multideterminant immunogens were successful. In all cases the large interline difference was shown to result from the additive effects of several independently segregating loci (polygenic regulation). However, important peculiarities were demonstrated in these original selections concerning either the cellular mechanisms operating or the effect of the selected genes on antibody responses to antigens unrelated with those used for the selection (multi-specific effect). In an attempt to improve and generalize the effect of selection, the 5 high and the 5 low lines were inter-crossed to obtain populations with a balanced proportion of the 5 genomes. These two populations were then submitted to selective breedings in which the phenotypic character was the weighted responses to pluri-antigen immunization. The data obtained in 16 consecutive generations of two selective breedings (general-primary, GP and general-secondary, GS, responses) carried out from these populations are reported. The genetic parameters of the response to GP and GS selections are compared with those obtained in the original selections. The final result of both GP and GS selections demonstrate a marked improvement of the high and low antibody production traits, both quantitatively (interline divergence) and qualitatively (multi-specific effect). The success of GP and GS selections agrees with the concept that distinct groups of genes are preferentially affected by selection according to the nature of the selection antigen and the immunization procedure.

Analysis of Variance↗

Neuroanatomical correlates of phonological processing of Chinese characters and alphabetic words: a meta-analysis.

We used the activation likelihood estimation (ALE) method to quantitatively synthesize data from 19 published brain mapping studies of phonological processing in reading, six with Chinese and 13 with alphabetic languages. It demonstrated high concordance of cortical activity across multiple studies in each written language system as well as significant differences of activation likelihood between languages. Four neural systems for the phonological processing of Chinese characters included: (1) a left dorsal lateral frontal system at Brodmann area (BA) 9; (2) the dorsal aspect of left inferior parietal system; (3) a bilateral ventral-occipitotemporal system including portions of fusiform gyrus and middle occipital gyrus; and (4) a left ventral prefrontal system covering the superior aspect of inferior frontal gyrus. For phonological processing of written alphabetic words, cortical areas identified here are consistent with the three neural systems proposed previously in the literature: (1) a ventral prefrontal system involving superior portions of left inferior frontal gyrus; (2) a left dorsal temporoparietal system including mid-superior temporal gyri and the ventral aspect of inferior parietal cortex (supramarginal region); and (3) a left ventral occipitotemporal system. Contributions of each of these systems to phonological processing in reading were discussed, and a covariant learning hypothesis is offered to account for the findings that left middle frontal gyrus is responsible for addressed phonology in Chinese whereas left temporoparietal regions mediate assembled phonology in alphabetic languages. Language form, cognitive process, and learning strategy drive the development of functional neuroanatomy.

Brain↗

Local control of T1 vocal cord cancer with radiation therapy: the importance of tumor character vs. treatment parameters.

Ninety-one patients with T1 vocal cord carcinoma received primary irradiation treatment. The 5- and 10-year determinate disease-free survival was 80%; the 5- and 10-year determinate survival including surgical salvage was 92%. Tumors involving more than one-half of a vocal cord or involving the anterior commissure or exhibiting an exophytic growth pattern had numerically, but not statistically, higher local failure rates than tumors without these characteristics. Precise radiation treatment technique appears more important for local control (LC) than tumor character. The crucial treatment factors for high LC with few radiation complications are reproducible daily patient positioning, use of contour-compensating devices (wedges), field size of 5 X 5 cm, and a radiation prescription with a time-dose fractionation value of 101 to 106.

Carcinoma, Squamous Cell↗

Xwnt-8 modifies the character of mesoderm induced by bFGF in isolated Xenopus ectoderm.

In Xenopus, growth factors of the TGF-beta, FGF and Wnt oncogene families have been proposed to play a role in generating embryonic pattern. In this paper we examine potential interactions between the bFGF and Xwnt-8 signaling pathways in the induction and dorsal-ventral patterning of mesoderm. Injection of Xwnt-8 mRNA into 2-cell Xenopus embryos does not induce mesoderm formation in animal cap ectoderm isolated from these embryos at the blastula stage, but alters the response of this tissue to mesoderm induction by bFGF. While animal cap explants isolated from non-injected embryos differentiate to form ventral types of mesoderm and muscle in response to bFGF, explants from Xwnt-8 injected embryos form dorsal mesodermal and neural tissues in response to the same concentration of bFGF, even if the ectoderm is isolated from the prospective ventral sides of embryos or from UV-ventralized animals. Our results support a model whereby dorso-ventral mesodermal patterning can be attained by a single mesoderm inducing agent, possibly bFGF, which is uniformly distributed across the prospective dorsal-ventral axis, and which acts in concert with a dorsally localized signal, possibly a Wnt protein, which either alters the response of ectoderm to induction or modifies the character of mesoderm after its induction.

Animals↗

Bioresorbable poly(ester-ether urethane)s from L-lysine diisocyanate and triblock copolymers with different hydrophilic character.

Bioresorbable linear poly(ester-ether urethane)s with different hydrophilic character were synthesized from block copolymers of poly(epsilon-caprolactone)-poly(ethylene oxide)-poly(epsilon-caprolactone) (PCL-PEO-PCL) as macrodiols, and L-lysine diisocyanate (LDI). A series of PCL-PEO-PCL triblock copolymers with different PEO and PCL chain length was obtained by reacting PEO with epsilon-caprolactone. Polyurethanes were synthesized by reacting the triblock copolymers with LDI in solution using stannous 2-ethylhexanoate as catalyst. The prepared triblock copolymers and polyurethanes were fully characterized by proton nuclear magnetic resonance spectroscopy, size exclusion chromatography, differential scanning calorimetry, and wide-angle X-ray diffraction. Water uptake, hydrolytic stability, and tensile properties of polyurethanes with different composition were evaluated and discussed in terms of the chain length and molecular weight of the polymers and its block components. Water uptake seems to depend on the ethylene oxide unit content of the polyurethane regardless of the triblock structure. Mechanical properties of the synthesized polymers were strongly affected by the molecular weight achieved during polymerization. The use of triblock macrodiols with different hydrophilicity allowed the preparation of a series of polyurethanes having a broad range of properties.

Biocompatible Materials↗

Single-step perturbations to calculate free energy differences from unphysical reference states: limits on size, flexibility, and character.

Relative free energies for a series of not too different compounds can be estimated accurately from a single simulation of an unphysical reference state that encompasses the characteristic molecular features of the compounds. Previously, this method has been applied to the calculation of free energies of solvation and of ligand binding for small molecules. In the present study we investigate the limits to the accuracy of the method by applying it to a realistic model of the binding of a set of rather large ligands to the protein factor Xa, a key protein in current efforts to design anticoagulation drugs. The evaluation of the binding free energies and conformations of nine derivatives of a biphenylamidino inhibitor leads to insights regarding the effect of the size, flexibility, and character of the unphysical part of the ligand in the reference state on the accuracy of the predicted binding free energies.

Journal Article↗

Secretory character of a group of isoproterenol-induced polypeptides in mouse parotid glands.

The secretory nature of the isoproterenol-induced mouse parotid polypeptides C, D, E, F, and G (molecular weights 64,000, 61,000, 51,500, 38,000, and 37,000, respectively) is documented. Polypeptides C, D, E, F, and G, accumulated in response to successive daily stimulations with isoproterenol, were detected in a fraction enriched in hypertrophic parotid acinar cells. These cells, characterized by an increased content of cytoplasmic granules, maintain a secretory responsiveness to isoproterenol, which has been evidenced by light microscopy, enzymatic analysis, and unidimensional SDS-polyacrylamide gel electrophoresis. Thus, a parallelism in the loss and recovery of both secretory granules, alpha-amylase and polypeptides C, D, E, F, and G, was observed. Moreover, after secretion stimulation, polypeptides C, D, E, F, and G were detected in the fluid collected directly from parotid gland cannulation. Given the secretory character of polypeptides C, D, E, F, and G, mechanisms explaining both their progressive accumulation along the chronic administration of isoproterenol, as well as their progressive disappearance observed after suspending that treatment, are discussed.

Animals↗

First-generation teeth in nonmammalian lineages: evidence for a conserved ancestral character?

The present study focuses on the main characteristics of first-generation teeth (i.e., the first teeth of the dentition to develop in a given position and to become functional) in representatives of the major lineages of nonmammalian vertebrates (chondrichthyans, actinopterygians, and sarcopterygians: dipnoans, urodeles, squamates, and crocodiles). Comparative investigations on the LM and TEM level reveal the existence of two major types of first-generation teeth. One type (generalized Type 1) is characterized by its small size, conical shape, atubular dentine, and small pulp cavity without capillaries and blood vessels. This type is found in actinopterygians, dipnoans, and urodeles and coincides with the occurrence of short embryonic periods in these species. The other type assembles a variety of first-generation teeth, which have in common that they represent miniature versions of adult teeth. They are generally larger than the first type, have more complex shapes, tubular dentine, and a large pulp cavity containing blood vessels. These teeth are found in chondrichtyans, squamates, and crocodiles, taxa which all share an extended embryonic period. The presence in certain taxa of a particular type of first-generation teeth is neither linked to their phylogenetic relationships nor to adult body size or tooth structure, but relates to the duration of embryonic development. Given that the plesiomorphic state in vertebrates is a short embryonic development, we consider the generalized Type 1 first-generation tooth to represent an ancestral character for gnathostomes. We hypothesize that an extended embryonic development leads to the suppression of tooth generations in the development of dentition. These may still be present in the form of rudimentary germs in the embryonic period. In our view, this generalized Type 1 first-generation teeth has been conserved through evolution because it represents a very economic and efficient way of building small and simple teeth adapted to larval life. The highly adapted adult dentition characteristic for each lineage has been possible only through polyphyodonty.

Animals↗

Grain boundary character distributions in Ni-16Cr-9Fe using selected area channeling patterns: methodology and results.

Selected area channeling patterns imaged on an SEM are digitized and displayed on the screen of a Macintosh computer, on which the user selects channeling bands that are measured to determine orientation. Grain boundary misorientations are found using the orientation information for pairs of grains adjacent at grain boundaries, and the boundaries are classified as low angle boundaries (LABs), coincident site lattice boundaries (CSLBs), or general boundaries (GHABs) based on the misorientation information. The technique was implemented to analyze the grain boundary character distributions (GBCDs) in Ni-16Cr-9Fe. The GBCDs of solution annealed material were similar to those expected in an aggregate of randomly oriented polycrystals. However, sequential thermomechanical treatments (5% tensile strain + 945 degrees C:75 min + 2% tensile strain + 890 degrees C:15 h + 3% tensile strain + 890 degrees C:20 h or 9% compressive strain + 890 degrees C:20 h + 9% compressive strain + 890 degrees C:20 h + 3% compressive strain + 890 degrees C:15 h) applied after the solution anneal lowered the proportions of GHABs in the GBCDs from 76-79% to 47-64%. The CSL-enhanced GBCDs of both the tensile-deformed samples and the compression-deformed sample appear to have evolved mainly through impingement of twin and twin-related boundaries during recrystallization; the CSL-enhanced GBCD of a compression-deformed sample appears to have been influenced by grain rotation processes to a greater degree than were the tensile-deformed samples The CSL boundaries in the CSL-enhanced GBCDs were, in general, closer to the exact CSL misorientations than were those in the near-random GBCDs of the solution annealed material. An analysis of the distribution of misorientation axes did not indicate any correlation between grain misorientation texture and GBCD evolution.

Alloys↗

Structure of a character and the evolution of butterfly eyespot patterns.

All butterfly eyespots appear to be formed by a similar developmental mechanism. Thus the great diversity of patterns observed across different species of butterfly has evolved through changes in the genetic modulation of this mechanism. Our descriptions of both the development of eyespots and the genetic variation for eyespot traits in an African butterfly, Bicyclus anynana, are used here to discuss the most appropriate ways of applying the character concept to the evolution of butterfly eyespot patterns. J. Exp. Zool. (Mol. Dev. Evol.) 291:93-104, 2001.

Animals↗

Ribozymes against TGFbeta1 reverse character of activated hepatic stellate cells in vitro and inhibit liver fibrosis in rats.

BACKGROUND/AIMS: Transforming growth factor beta (TGFbeta1) is considered the key mediator in the process of liver fibrosis. The purpose of this investigation was to evaluate the activity of ribozymes against TGFbeta1 in a cell-free system and activated hepatic stellate cells (HSCs), and antifibrotic effect in activated HSCs in vitro and in rats. METHODS: Three ribozymes targeting against TGFbeta1 mRNA were designed, and then cloned into the U1 snRNA expression cassette. The chimeric ribozymes were selected for the analysis of their performances in activated HSCs through the detection of their cleavage activities in a cell-free system. After ribozyme-encoding plasmids had been transfected into HSC-T6 cells, the effects of ribozymes on activated HSCs were evaluated through the analysis of proliferation, activation and collagen deposition of HSC-T6. The adenoviral vector expressing the ribozymes was constructed, and then delivered into rat models of hepatic fibrosis induced by carbon tetrachloride. RESULTS: TGFbeta1 expression was efficiently down-regulated in activated HSCs by U1 snRNA chimeric ribozymes which possessed perfect cleavage activity in a cell-free system. Further studies demonstrated that U1 snRNA chimeric ribozymes inhibited the synthesis of collagen I, reduced deposition of collagen I, suppressed BrdU incorporation, but had no effect on desmin and alpha-SMA expression in transfected HSC-T6 cells. Histological analysis demonstrated that the adenoviral vector expressing ribozyme (Rz803) could alleviate fibrotic pathology in rats treated with carbon tetrachloride. CONCLUSIONS: The anti-TGFbeta1 ribozymes could reverse the character of activated HSCs in vitro and improve fibrotic pathology in vivo. It indicated that TGFbeta1 could be considered as a novel candidate for a therapeutic agent against hepatic fibrosis.

Animals↗

New characters in the Gnathostomulid mouth parts revealed by scanning electron microscopy.

An analysis with SEM of the mouth parts of 16 species belonging to 10 genera of Gnathostomulida resulted in the following new characters and conclusions: 1) At least in the genus Haplognathia, jaw teeth that are visible by conventional light microscopy are composed of the same aggregated needle-like denticles that are found, often in large numbers, on the basal plates of many filospermoid species. 2) Other new ultrastructural tooth features include the tricuspid basal plate teeth in Problognathia minima, tripartite teeth in Austrognathia and Austrognatharia, and the clear separation, in the Gnathostomula basal plate, of a mediodorsal set of teeth from a more extensive rostroventral set. 3) Three rows of teeth, as typical for Gnathostomulidae and Austrognathiidae, are also present in the filospermoid Haplognathia filum. 4) The wide range of geographic variation in Haplognathia ruberrima is confirmed by significant differences in jaw teeth between specimens from Belize and Bermuda. 5) A compartmentalized involucrum is present in Labidgonathia longicollis. 6) A pair of lamellae addentales, until now only known from Valvognathia pogonostoma, was found in Tenuignathia rikerae, Problognathia minima, and probably also Labidognathia rikerae. 7) In all gnathostomulids, the lamella symphysis is composed of identical rods that are considered homologous with those in the mouth parts of Rotifera and Micrognathozoa.

Animals↗

Location of the ureteral openings in the cloacas of tinamous, some ratite birds, and crocodilians: a primitive character.

Cloacas of 67 avian species, of both sexes, from various habitats and differing dietary habits, were examined macro- and microscopically to investigate possible variation in the location of the ureteral openings. Differing from most birds studied, in adult male Rhea americana and several tinamous species the ureters were found to open into the coprodeum. In these species the urodeum receives only the vas deferens or oviduct. Similarly, in crocodiles Caiman crocodilus yacare, but not in lizards Tropidurus montanus and snakes Crotalus durissus terrificus, the ureters empty into the coprodeum. This similarity between ancient birds (ratites and tinamous) and crocodiles may indicate a primitive character linking reptiles and birds. This unusual position of the ureteral orifice can represent an adaptation to facilitate urine collection into the coprodeum and large intestine. Another possibility is that this variation in ureter position is a male reproductive strategy to avoid the mixture of urine and semen in the cloaca. There were no evident correlations between the location of the ureteral openings and the birds' habitat, diet, or histology of the coprodeal mucosa. The occurrence of a phallus in eight species of birds was detected, as well as a peculiar vascularization related to the coprodeal epithelium of anseriformes. Together, these data add to the scarce information about the morphophysiology of the avian cloaca, and also contribute to clarify avian phylogenetic linkages.

Animals↗

Description of a cranial endocast from a fossil platypus, Obdurodon dicksoni (Monotremata, Ornithorhynchidae), and the relevance of endocranial characters to monotreme monophyly.

A digital cranial endocast of the Miocene platypus Obdurodon dicksoni was extracted from high-resolution X-ray computed tomography scans. This endocast represents the oldest from an unequivocal member of either extant monotreme lineage and is therefore important for inferring character support for Monotremata, a clade that is not well diagnosed. We describe the Obdurodon endocast with reference to endocasts extracted from skulls of the three species of extant monotremes, particularly Ornithorhynchus anatinus, the duckbill platypus. We consulted published descriptions and illustrations of whole and sectioned brains of monotremes to determine which external features of the nervous system are represented on the endocasts. Similar to Ornithorhynchus, well-developed parafloccular casts and reduced olfactory bulb casts are present in the Obdurodon endocast. Reduction of the olfactory bulbs in comparison with tachyglossids and therian mammals is a potential apomorphy for Ornithorhynchidae. The trigeminal nuclei, ganglia, and nerves (i.e., trigeminal complex) are enlarged in Obdurodon, as evidenced by their casts on the endocast, as is the case in the extant platypus. The visibility of enlarged trigeminal nucleus casts on the endocasts of Obdurodon and Ornithorhynchus is a possible synapomorphy of Ornithorhynchidae. Electroreception and enlargement of the trigeminal complex are possible synapomorphies for Monotremata.

Animals↗

Effects of solvent medium on solubility III: Hydrophilic-lipophilic character exhibited by some functional groups having oxygen or nitrogen in ethanol-water.

Solubility data of nine derivatives of the structure p-X1-C6H4-X2 in ethanol-water at 25 degrees C are reported. The correlation of such sets of data by log Sy = Py X log Sx + C yields the medium effect parameter Py for a variety of functional groups possessing either oxygen or nitrogen. Py accounts for the hydrophilic-lipophilic character exhibited by each group.

Chemical Phenomena↗

Identification of character-impact odorants in coriander and wild coriander leaves using gas chromatography-olfactometry (GCO) and comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC x GC-TOFMS).

The essential oil of coriander leaves (Coriandrum sativum) and wild coriander leaves (Eryngium foetidum) grown in Fiji was obtained by steam distillation. The aroma profiles were characterised using gas chromatography-olfactometry (GCO) and CharmAnalysis. The character-impact odorants were identified using comprehensive two-dimensional gas chromatography (GC x GC) combined with time-of-flight mass spectrometry (TOFMS). During GCO analysis, the co-elution of E-2-alkenals and E-2-alken-1-ols resulted in the perception of 'odour-clusters'. The most important odorants in C. sativum were found to be Z-2-decenal, a co-eluting odour-cluster (E-2-dodecenal, E-2-dodecen-1-ol, and 1-dodecanol), beta-ionone, eugenol, and E-2-decenal. E-2-decen-1-ol was the most abundant compound in C. sativum (26.0% TIC) but only contributed 0.39% of the total odour activity. The most abundant compound in E. foetidum was E-2-dodecenal (63.5% TIC), which also contributed the most odour activity (52.9%). Other important odorants were either eugenol or a trimethylbenzaldehyde isomer, beta-ionone, Z-4-dodecenal, dodecanal, and E-2-tetradecenal. GC x GC-TOFMS allowed the identification of 42 and 20 compounds not previously reported in the literature for C. sativum and E. foetidum, respectively. In particular, beta-ionone was determined to be an important odorant in both samples but could not be identified with GC-qMS.

Chromatography, Gas↗

Changes in the pore character of silicas caused by surface bonding and polymer coating.

The pore character of packings for liquid chromatography, especially reversed-phase (RPLC) packings, has been studied by means of the nitrogen adsorption method (BET method). Micro-spherical silica gels with 9, 12, 30, 40 and 50 nm average pore diameter have been used as carriers. These silica gels have been modified with monochlorodimethyloctadecylsilane and several polymers (polyoctadecylmethacrylate-methylmethacrylate co-polymer, polyacrylamide gel, polyvinyl alcohol, poly-2-hydroxyethyl-methacrylate). A larger decrease in the specific surface area values was observed in the case of the polymer coating with the polyoctadecylmethacrylate-methylmethacrylate co-polymer compared with the derivatization by silanes or the modification with polymers without C18-groups. A new approach has been suggested to explain some questions concerning the interpretation of the data obtained during the measurements of the pore characteristics of the derivatized packings. An attempt has been made to reveal peculiarities connecting values of the measured surface of RP-packings with the specific surface area values of the initial silica, as well as with the chromatographically accessible surface.

Journal Article↗