The central projections of mesothoracic sensory neurons in wild-type Drosophila and bithorax mutants

Sensory axons entering the CNS from large campaniform sensilla on the normal, mesothoracic wings of four-winged flies of the genotype $\text{bx}{}^3\text{pbx}\text{Ubx}{}^{130}$ follow the same two tracts as do the corresponding axons in wild-type flies. However, they produce more branches along the ventromedial tract (including some in the mesothoracic neuromere), more fibers crossing the midline in the metathorax, and several other modifications of the wild-type pattern. No morphological differences between the receptors in normal and mutant flies could be detected, even with the SEM. The extra branching and other altered characteristics are present in bithorax flies which are also genetically wingless and do not form the homeotic appendages, so they appear to be due to the $\text{bx}{}^3\text{pbx}\text{Ubx}{}^{130}$ or $\text{bx}{}^3\text{Ubx}{}^{130}$ genotype and not to some effect of the axons from the homeotic wings.     

The design, synthesis and physical chemical properties of novel human vasopressin V2-receptor antagonists optimized for parenteral delivery

Ionizable groups were introduced onto the 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine scaffold of the vasopressin V2-antagonist WAY-VPA-985 in the search for molecules optimized for parenteral formulation. The synthesis and structure activity relationships (SAR) are presented together with solubility data in a model parenteral system. The amine, WAY-140288 (4f), was chosen for further development. p6     

Tyrosine-phosphorylated plakoglobin is associated with desmogleins but not desmoplakin after epidermal growth factor receptor activation

Tyrosine phosphorylation of junctional components has been proposed as a mechanism for modulating cell-cell adhesion. Although a correlation exists between the tyrosine phosphorylation of the adherens junction protein beta-catenin and loss of classical cadherin-mediated adhesion, the effects of tyrosine phosphorylation on the function of the adherens junction and desmosome-associated protein plakoglobin is unknown. In the present study, we investigated the effects of epidermal growth factor receptor (EGFR) tyrosine kinase activation on the subcellular distribution of plakoglobin and its association with its junctional binding partners. Long term epidermal growth factor (EGF) treatment of A431 cells revealed a modest decrease in the cytoskeleton-associated pool of plakoglobin (Pg) and a corresponding increase in the cytosolic pool of Pg. After short term EGF treatment, plakoglobin was rapidly phosphorylated, and tyrosine-phosphorylated Pg was distributed predominantly in a membrane-associated Triton X-100-soluble pool, along with a co-precipitating high molecular weight tyrosine-phosphorylated protein identified as desmoglein 2. Analysis of deletion and point mutants defined the primary EGFR-dependent targets as one or more of three C-terminal tyrosine residues. Whereas phosphorylated Pg remained associated with the desmoglein tail after both short and long term EGFR activation, no phosphorylated Pg was found associated with the N-terminal Pg-binding domain (DPNTP) of the intermediate filament-associated protein, desmoplakin. Together these results are consistent with the possibility that EGF-dependent tyrosine phosphorylation of Pg may modulate cell-cell adhesion by compromising the link between desmosomal cadherins and the intermediate filament cytoskeleton.     

Identification and chromosomal localisation by fluorescence in situ hybridisation of human gene of phosphoinositide-specific phospholipase C beta(1)

Members of phosphoinositide-specific phospholipase C (PLC) families are central intermediary in signal transduction in response to the occupancy of receptors by many growth factors. Among PLC isoforms, the type beta(1) is of particular interest because of its reported nuclear localisation in addition to its presence at the plasma membrane. It has been previously shown that both the stimulation and the inhibition of the nuclear PLCbeta(1) under different stimuli implicate PLCbeta(1) as an important enzyme for mitogen-activated cell growth as well as for murine erythroleukaemia cell differentiation. The above findings hinting at a direct involvement of PLCbeta(1) in controlling the cell cycle in rodent cells, and the previously reported mapping of its gene in rat chromosome band 3q35-36, a region frequently rearranged in rat tumours induced by chemical carcinogenesis, prompted us to identify its human homologue. By screening a human foetal brain cDNA library with the rat PLCbeta(1) cDNA probe, we have identified a clone homologous to a sequence in gene bank called KIAA 0581, which encodes a large part of the human PLCbeta(1). By using this human cDNA in fluorescence in situ hybridisation on human metaphases, it has been possible to map human PLCbeta(1) on chromosome 20p12, confirming the synteny between rat chromosome 3 and human chromosome 20 and providing a novel locus of homology between bands q35-36 in rat and p12 in man. Since band 20p12 has been recently reported amplified and/or deleted in several solid tumours, the identification and chromosome mapping of human PLCbeta(1) could pave the way for further investigations on the role exerted both in normal human cells and in human tumours by PLCbeta(1), which has been shown to behave as a key signalling intermediate in the control of the cell cycle.     

An accumulation of IGF-1 and IGF-binding proteins in human umbilical cord

It is known that extracellular matrix components (ECM) may serve as a storage site to concentrate and stabilize growth factors in the vicinity of cells. IGF-I is expressed in most fetal tissues and it is involved in anabolic effects on protein and sulphated glycosaminoglycans biosynthesis, cell proliferation and differentiation. We demonstrated that human umbilical cord (UC) tissues contain large amounts of IGF-I and IGF-I-binding proteins (BP-3 and BP-1). Particularly Wharton's jelly appears to be an abundant reservoir of IGF-I and BPs. Relatively low amount of cells and large amounts of collagen and glycosaminoglycans in UC tissues (especially in Wharton's jelly) suggest that IGF-I may play a major role in stimulation of these cells to produce ECM components. The specific BPs in these tissues may be important modulators of IGF-I action during fetal development.     

Axon guidance in cultured wing discs and disc fragments of Drosophila

The sensory neurons of the Drosophila wing differentiate during the initial stages of metamorphosis, appearing in the imaginal wing disc as it everts and flattens. These identifiable neurons arise in a stereotyped sequence, and lay down a specific pattern of axon bundles which travel proximally to the CNS. In several locations, the early arising "pioneer" neurons send axons in the direction of more proximal pioneer neurons, later joining with these to form continuous peripheral nerves. It is possible that distal neurons can contact more proximal neurons by random filopodial search, and use this information to guide axonal outgrowth. To test this "guidepost" hypothesis, everting wing discs were raised in vitro to allow surgical manipulation. Neural outgrowth was largely normal in vitro, though growth of the wing was stunted. If such discs were cut into proximodistal fragments before or at the time of initial axonogenesis, neural outgrowth remained normal: distal axons still grew in the direction of the now missing proximal neurons. Thus, proximal neurons are not necessary for the correct guidance of distal neurons in the developing wing.     

Axonal polarity in Drosophila wings with mutant cuticular polarity patterns

In Drosophila melanogaster certain mutations alter the polarity of trichomes and bristles, cuticular structures secreted by the epithelial cells of the adult fly. Since sensory neurons arise from epithelial cell precursors, and sensory axons grow along the inner faces of epithelial cells, we have studied the developing wings of these mutants to see whether the change in epithelial cell polarity has an influence on the direction of axon outgrowth. The nerve patterns formed in the mutants prickled, inturned, and frizzled, however, were largely normal, indicating that in these cases the polarity of the cuticular structures produced by the epithelial cells is altered without any effect on the polarity of the associated axons.     

A new case of partial 2p trisomy due to de novo interstitial duplication 2p21-22

We report on a case of "de novo" interstitial duplication of bands 2p21-22 in a 31-month-old female with mild mental retardation and dysmorphism. Cytogenetic investigations were performed on peripheral blood by adding 5-BrdU and 5-FdU. Measurements of enzymatic activity of malate dehydrogenase, whose gene has been mapped on the band 2p23, added reliability to the identification of bands 2p21-22 as the duplicated segment. The authors suggest that the duplication of this segment is able to cause the clinical picture of the syndrome of partial 2p trisomy.     

Clinical and cytogenetic staging of chronic myeloid leukemia. Philadelphia positive

A cooperative study between clinical and cytogenetic steps in 44 patients with Ph'+ CGL is reported in order to verific the usefulness of the cytogenetic screening for the diagnosis and the right classification of the patients. The study of the clinical steps is carried out on the basis of the parameters suggested by Tura and coll.; in the one of the cytogenetic steps Sandberg classification modified by the Authors is adopted. In 40 cases the comparison shows a marrow correspondence between clinical and cytogenetic steps. In fact the overage survival in the classical true steps of the disease is almost the sance in the 1st and 2nd step. In the 3rd step the survival is strongly reduced meaning that the more chromosome alterations are observed the more survival is reduced.