Vertebrate development: Et in Arkadia

The similarities in organiser formation in Xenopus and mouse embryos have remained elusive. Recent evidence suggests a common mechanism, in which an intracellular protein, Arkadia, is required for formation of the mouse organiser and potentiates the effects of the signalling protein Nodal.     

Temporal progression of hypothalamic patterning by a dual action of BMP

In the developing chick hypothalamus, Shh and BMPs are expressed in a spatially overlapping, but temporally consecutive, manner. Here, we demonstrate how the temporal integration of Shh and BMP signalling leads to the late acquisition of Pax7 expression in hypothalamic progenitor cells. Our studies reveal a requirement for a dual action of BMPs: first, the inhibition of GliA function through Gli3 upregulation; and second, activation of a Smad5-dependent BMP pathway. Previous studies have shown a requirement for spatial antagonism of Shh and BMPs in early CNS patterning; here, we propose that neural pattern elaboration can be achieved through a versatile temporal antagonism between Shh and BMPs.     

Tensile strength of bone fixation of hydroxyapatite coated Schanz screws of the Heidelberg External Fixation System (HEFS)--comparative torque measurements in clinical use and in cadaver tibia]

It is claimed in the literature that hydroxyapatite(HA)-coated screws of external fixators have superior fixation strength in bone, which is postulated to lead to a substantial decrease in loosening and infection rates. We report on a study of the maximum torque values developed while inserting and removing 30 HA-coated Schanz screws of 8 Heidelberg external fixation systems applied to the tibia to correct leg length differences and axial deformities. The infection rate was determined in accordance with defined criteria, and was found to be about 20% for the HA-coated screws. Screws without infection showed an extraction torque above insertion torque, screws with infection an extraction torque below. A significant correlation (p = 0.05) was seen between infection and decrease in fixation strength (quotient: loosening torque/tightening torque). To exclude the impact of such biological processes as osteointegration and bone remodelling, the clinical results were compared with the torques measured for coated and uncoated Schanz screws in a human cadaveric tibia. A significantly higher fixation strength in bone was found for HA-coated screws in comparison with uncoated screws (p = 0.002). These data warrant a clinical study directly comparing HA-coated and uncoated Schanz screws.     

Airway patterning: A paradigm for restricted signalling.

Intercellular signalling is limited by the range of cell responsiveness, often mediated by repressors. A recently identified repressor, Sprouty, inhibits MAP kinase signalling in flies, mice and humans and has a conserved function in patterning the airways of these divergent species.     

Histological and immunohistochemical effects of Curcuma longa on activation of rat hepatic stellate cells after cadmium induced hepatotoxicity

The liver is a target for toxic chemicals such as cadmium (Cd). When the liver is damaged, hepatic stellate cells (HSC) are activated and transformed into myofibroblast-like cells, which are responsible for liver fibrosis. Curcuma longa has been reported to exert a hepato-protective effect under various pathological conditions. We investigated the effects of C. longa administration on HSC activation in response to Cd induced hepatotoxicity. Forty adult male albino rats were divided into: group 1 (control), group 2 (Cd treated), group 3 (C. longa treated) and group 4 (Cd and C. longa treated). After 6 weeks, liver specimens were prepared for light and electron microscopy examination of histological changes and immunohistochemical localization of alpha smooth muscle actin (αSMA) as a specific marker for activated HSC. Activated HSC with a positive αSMA immune reaction were not detected in groups 1 and 3. Large numbers of activated HSC with αSMA immune reactions were observed in group 2 in addition to Cd induced hepatotoxic changes including excess collagen deposition in thickened portal triads, interlobular septa with hepatic lobulation, inflammatory cell infiltration, a significant increase in Kupffer cells and degenerated hepatocytes. In group 4, we observed a significant decrease in HSC that expressed αSMA with amelioration of the hepatotoxic changes. C. longa administration decreased HSC activation and ameliorated hepatotoxic changes caused by Cd in adult rats.     

Inhibition of interferon secretion by vinblastine

The plant alkaloids vinblastine and colchicine are known to arrest cells in mitosis by virtue of their binding to spindle protein. These drugs are also capable of binding to microtubule protein and causing these structures to disaggregate into nonfunctional subunits (1, 2). Microtubular structures are thought to be involved in the secretory process of a number of proteins including insulin (7), collagen (4), and thyroid hormone (12). In this report we present our findings on the effects of these two drugs on the synthesis and secretion of interferon in a high producing human foreskin fibroblast strain (FS-4) (11).     

Insertion elements and transitions in cloned mouse mammary tumour virus DNA: further delineation of the poison sequences.

The provirus of mouse mammary tumour virus (MMTV) is reputed to contain sequences within the viral gag gene that prevent or inhibit its propagation as a recombinant DNA clone in Escherichia coli. Here we report the successful isolation of several lambda and plasmid clones comprising the 5' virus-host DNA junction fragments from integrated MMTV proviruses in BR6 mice. Although the lambda clones appeared intact, almost all of the plasmids were found to contain the bacterial insertion sequences IS1 or IS2 within a small region of the gag gene. One nondisrupted clone was recovered which had undergone multiple G to A transitions, some of which created stop codons in gag. These results have provided more precise information as to the location of the poison sequences and are discussed in relation to possible explanations for the phenomenon.     

Early Stages of Notochord and Floor Plate Development in the Chick Embryo Defined by Normal and Induced Expression of HNF-3β

We have cloned a cDNA encoding the chick HNF-3β gene and have used RNA and antibody probes that detect HNF-3β to monitor the normal and induced expression of the gene in early embryos. HNF-3β is expressed in Koller's sickle, at the onset of primitive streak formation, and later in Hensen's node. At neural plate and neural tube stages, HNF-3 β is expressed transiently in the notochord and is then expressed by floor plate cells. Prospective floor plate cells that are located in the epiblast immediately anterior to Hensen's node prior to its regression do not express HNF-3β, providing evidence that floor plate fate is normally determined only after these cells populate the midline of the neural plate and overlie the notechord. Removal of the notochord in vivo prevents floor plate development and in this condition HNF-3β is not expressed by cells at the ventral midline of the neural tube. Notochord grafts induce ectopic floor plate development and ectopic neural expression of HNF-3 β. In vitro, neural plate explants are induced to express HNF-3β by notochord cells in a contact-dependent but cycloheximide-resistant manner, providing evidence that expression of HNF-3 β is a direct response of neural plate cells to notochord-derived inducing signals.