Distribution of Major Brain Gangliosides in Olfactory Tract of Frogs

Gangliosides are major cell-surface determinants in the central nervous system (CNS) of vertebrates, found both in neuronal and glial cell membranes. Together with cholesterol and glycosylphosphatidylinositol (GPI) – anchored proteins, gangliosides are involved in organization of plasma membrane microdomains. Based on biochemical studies, frog brain was previously described as having low quantities of gangliosides and their distribution pattern in specific brain regions was unknown. Using highly specific monoclonal antibodies generated against four major brain gangliosides (GM1, GD1a, GD1b and GT1b), we examined the distribution of these molecules in CNS of four different species of frogs (Rana esculenta, Rana temporaria, Bufo bufo and Bufo viridis). We also studied the distribution of myelin- associated glycoprotein (MAG), an inhibitor of axonal regeneration, which is a ligand for gangliosides GD1a and GT1b. Our results show that ganglioside GD1a is expressed in neurons of olfactory bulb in all studied animals. In the brain of Rana sp., GD1a is expressed in the entire olfactory pathway, from olfactory bulbs to amygdala, while in Bufo sp. GD1a is restricted to the main olfactory bulb. Furthermore, we found that most of myelinated pathways in frogs express MAG, but do not express GD1a, which could be one of the reasons for better axon regeneration of neural pathways after CNS injury in amphibians in comparison to mammals

Eksploatacija i karakteristike prometa ISDN u Hrvatskoj

Uvođenje ISDN-a u hrvatsku telefonsku mrežu osnovna je tema ovoga rada. Opisana je telefonska mreža kao osnova za ISDN te aspekti ISDN-a. Navedeni su primjeri primjene ISDN usluga te koju je ulogu imao ISDN u povezivanju Interneta i javne telefonske mreže. Dani su kvalitativni prikazi ukupnog prometa i posebno prometa prema Internetu na pristupnim i tranzitnim centralama. Kao slijedeći korak u razvoju telekomunikacijske mreže, predstavljena je konvergencija dviju mreža i usluga: telefonske i podatkovne. Predstavljen je mogući koncept mreže nove generacije. Kao nezaobilazna funkcija u mreži opisano je usmjeravanje prometa te moguća unaprijeđenja prema dinamičkom i adaptivnom usmjeravanju. Na već izrađenom modelu za testiranje metoda usmjeravanja (LAG) napravljeni su eksperimenti koji pokazuju usporedne rezultate simulacije fiksnog usmjeravanja i usmjeravanja na osnovu automata sa svojstvom učenja.The basic subject of this paper is the implementation of ISDN to the Croatian PSTN network. Public Switched Telephony Network is described as a basis for ISDN. The implementation of ISDN services is presented through all relevant aspects. Further, the examples of ISDN usage and the impact of ISDN on connection of Internet and PSTN are mentioned. Description of the network and ISDN implementation are followed by qualitative presentations of the total and Internet traffic on the local and transit exchanges. The next step in network development is presented through the convergence of the PSTN and data networks and services. Possible concept of the next generation network is described. As traffic routing is an important function in the network, its improvement towards dynamic and adaptive routing is presented. Simulations of fixed routing and the routing based on learning automata are performed on the already designed mogul (LAG). The results of simulations that are presented serve for the comparison of routing methods

Eksploatacija i karakteristike prometa ISDN u Hrvatskoj

Uvođenje ISDN-a u hrvatsku telefonsku mrežu osnovna je tema ovoga rada. Opisana je telefonska mreža kao osnova za ISDN te aspekti ISDN-a. Navedeni su primjeri primjene ISDN usluga te koju je ulogu imao ISDN u povezivanju Interneta i javne telefonske mreže. Dani su kvalitativni prikazi ukupnog prometa i posebno prometa prema Internetu na pristupnim i tranzitnim centralama. Kao slijedeći korak u razvoju telekomunikacijske mreže, predstavljena je konvergencija dviju mreža i usluga: telefonske i podatkovne. Predstavljen je mogući koncept mreže nove generacije. Kao nezaobilazna funkcija u mreži opisano je usmjeravanje prometa te moguća unaprijeđenja prema dinamičkom i adaptivnom usmjeravanju. Na već izrađenom modelu za testiranje metoda usmjeravanja (LAG) napravljeni su eksperimenti koji pokazuju usporedne rezultate simulacije fiksnog usmjeravanja i usmjeravanja na osnovu automata sa svojstvom učenja.The basic subject of this paper is the implementation of ISDN to the Croatian PSTN network. Public Switched Telephony Network is described as a basis for ISDN. The implementation of ISDN services is presented through all relevant aspects. Further, the examples of ISDN usage and the impact of ISDN on connection of Internet and PSTN are mentioned. Description of the network and ISDN implementation are followed by qualitative presentations of the total and Internet traffic on the local and transit exchanges. The next step in network development is presented through the convergence of the PSTN and data networks and services. Possible concept of the next generation network is described. As traffic routing is an important function in the network, its improvement towards dynamic and adaptive routing is presented. Simulations of fixed routing and the routing based on learning automata are performed on the already designed mogul (LAG). The results of simulations that are presented serve for the comparison of routing methods

Distribution of Major Brain Gangliosides in Olfactory Tract of Frogs

Gangliosides are major cell-surface determinants in the central nervous system (CNS) of vertebrates, found both in neuronal and glial cell membranes. Together with cholesterol and glycosylphosphatidylinositol (GPI) – anchored proteins, gangliosides are involved in organization of plasma membrane microdomains. Based on biochemical studies, frog brain was previously described as having low quantities of gangliosides and their distribution pattern in specific brain regions was unknown. Using highly specific monoclonal antibodies generated against four major brain gangliosides (GM1, GD1a, GD1b and GT1b), we examined the distribution of these molecules in CNS of four different species of frogs (Rana esculenta, Rana temporaria, Bufo bufo and Bufo viridis). We also studied the distribution of myelin- associated glycoprotein (MAG), an inhibitor of axonal regeneration, which is a ligand for gangliosides GD1a and GT1b. Our results show that ganglioside GD1a is expressed in neurons of olfactory bulb in all studied animals. In the brain of Rana sp., GD1a is expressed in the entire olfactory pathway, from olfactory bulbs to amygdala, while in Bufo sp. GD1a is restricted to the main olfactory bulb. Furthermore, we found that most of myelinated pathways in frogs express MAG, but do not express GD1a, which could be one of the reasons for better axon regeneration of neural pathways after CNS injury in amphibians in comparison to mammals

MiR-4649-5p acts as a tumor-suppressive microRNA in triple negative breast cancer by direct interaction with PIP5K1C, thereby potentiating growth-inhibitory effects of the AKT inhibitor capivasertib

Abstract Background Triple negative breast cancer (TNBC) is a particularly aggressive and difficult-to-treat subtype of breast cancer that requires the development of novel therapeutic strategies. To pave the way for such developments it is essential to characterize new molecular players in TNBC. MicroRNAs (miRNAs) constitute interesting candidates in this regard as they are frequently deregulated in cancer and contribute to numerous aspects of carcinogenesis. Methods and results Here, we discovered that miR-4649-5p, a miRNA yet uncharacterized in breast cancer, is associated with better overall survival of TNBC patients. Ectopic upregulation of the otherwise very low endogenous expression levels of miR-4646-5p significantly decreased the growth, proliferation, and migration of TNBC cells. By performing whole transcriptome analysis and physical interaction assays, we were able to identify the phosphatidylinositol phosphate kinase PIP5K1C as a direct target of miR-4649-5p. Downregulation or pharmacologic inhibition of PIP5K1C phenocopied the growth-reducing effects of miR-4649-5p. PIP5K1C is known to play an important role in migration and cell adhesion, and we could furthermore confirm its impact on downstream PI3K/AKT signaling. Combinations of miR-4649-5p upregulation and PIP5K1C or AKT inhibition, using the pharmacologic inhibitors UNC3230 and capivasertib, respectively, showed additive growth-reducing effects in TNBC cells. Conclusion In summary, miR-4649-5p exerts broad tumor-suppressive effects in TNBC and shows potential for combined therapeutic approaches targeting the PIP5K1C/PI3K/AKT signaling axis

ALYREF, a novel factor involved in breast carcinogenesis, acts through transcriptional and post-transcriptional mechanisms selectively regulating the short NEAT1 isoform

The RNA-binding protein ALYREF (THOC4) is involved in transcriptional regulation and nuclear mRNA export, though its role and molecular mode of action in breast carcinogenesis are completely unknown. Here, we identifed high ALYREF expression as a factor for poor survival in breast cancer patients. ALYREF signifcantly infuenced cellular growth, apoptosis and mitochondrial energy metabolism in breast cancer cells as well as breast tumorigenesis in orthotopic mouse models. Transcriptional profling, phenocopy and rescue experiments identifed the short isoform of the lncRNA NEAT1 as a molecular trigger for ALYREF efects in breast cancer. Mechanistically, we found that ALYREF binds to the NEAT1 promoter region to enhance the global NEAT1 transcriptional activity. Importantly, by stabilizing CPSF6, a protein that selectively activates the post-transcriptional generation of the short isoform of NEAT1, as well as by direct binding and stabilization of the short isoform of NEAT1, ALYREF selectively fne-tunes the expression of the short NEAT1 isoform. Overall, our study describes ALYREF as a novel factor contributing to breast carcinogenesis and identifes novel molecular mechanisms of regulation the two isoforms of NEAT1