Knowledge diffusion social network is fundamental for efficient science policy

Development of a coherent science policy is a complex issue, especially within the strategic framework that has an ambition to build up the development of economy and so iety based on knowledge-intensive activities. The basis of such a policy is development of a dynamic (innovation) knowledge diffusion social network. Development of such a network require redefinition of the systemof research careers and instruments for its development, modernization of public research institutions, investments in innovation diffusion mechanisms through alignment of educational policies and lifelong learning strategies, and development of policies and instruments for bidirectional technology transfer (from university to industry and vice versa). In this contribution, the elements of a knowledge diffusion social network in Croatia and Croatian innovation capacities are discussed from the perspectives of policies and instruments for development of research careers

Cytoplasmic virion assembly compartment of betaherpesviruses

During their life cycle, betaherpesviruses extensively reorganize the membranous system of the cell in order to develop a unique cytoplasmic environment of virion production ("virus factory"), known as cytoplasmic virion assembly compartment (cVAC). The betaherpesvirus cVAC has been studied both in human and murine cytomegalovirus (CMV) infected cells as they are considered to be models for betaherpesviruses biology. Studies of the cVAC were mainly based on electron microscopy and immunofluorescence tools, and in the previous decade, they have expanded to the use of new technologies and systems approaches (i.e., transcriptomics, proteomics, lipidomics), which led to the acquisition of a vast amount of data. Despite the immense expansion of knowledge about membranous organelle system, including a large amount of data derived from CMV infected cells, the organization and biogenesis of the cVAC remain unclear. Accordingly, very little is known about the processes of a final stage of CMV maturation and the virion egress. This minireview summarizes current knowledge about the biogenesis of the betaherpesvirus factory from the already existent endosomal compartments. &nbsp;</p

The Science at Croatian Universities: a Gloomy View through SCIsearch and MEDLINE

Cilj rada. Usporedba znanstvenih članaka tiskanih tijekom zadnjih deset godina u kojima su autori znanstvenici na sveučilištima u Zagrebu, Rijeci, Osijeku, Splitu s onima na Sveučilištu u Ulmu (Njemačka) i Gracu (Austrija). Metode. Analiziran je broj radova dobiven pretraživanjem SCIsearch (Institute for Scientific Information (ISI) baze podataka i MEDLINE. Rezultati. Uspoređujući ukupni broj radova koje registrira SCIsearch, znanstvenici na regionalnim hrvatskim sveučilištima objavili u tijeku desetogodišnjeg razdoblja znatno manje radova od ostalih sveučilišta uključenih u istraživanje. Podatak da su znanstvenici na našim sveučilištima objavili samo 0,42 (Osijek), 0,55 (Rijeka) i 0,75 (Split) radova po znastveniku tijekom desetogodišnjeg razdoblja sam za sebe dosta govori. Znastvenici Sveučilita u Zagrebu objavili su u istom razdoblju 1,65 radova po znanstveniku, uto je ipak vrlo malo ako se usporedi s produktivnošću znanstvenika na Sveučilištu u Ulmu (6,6 radova po znanstveniku). Slični se rezultati dobiju ako se napravi usporedba broja radova objavljenih na 1000 studenata kao mjere veličine sveučilišta. Zaključak. Neovisno koji se pokazatelj koristio za usporedbu znanstvene razvijenosti, sva tri hrvatska regionalna sveučilišta bitno zaostaju za Sveučilištem u Zagrebu. Držimo da je razvijenost znanstvenog rada dosegla tako nisku razinu da to samo po sebi dovodi u pitanje njihov opstanak i daljnji razvoj. Glavne kočnice daljnjeg razvoja hrvatske znanosti su: (a) manjak vrhunskih znanstvenika koji bi pokrenuli razvoj, (b) sporost u provođenju reforme hrvatskih sveučilišta uz brojna opiranja pri samom začetku. Pri provođenju znanstvene politike, posebice pri probiru znanstvenih kadrova, treba čim prije uvesti univerzalne znanstvene kriterije. Novi Zakon o znanosti kao i Nacionalni znanstveni program pretstavljaju dobru osnovu za novi početak.Aim. Comparison of scientific articles published during the last 10 years by scientists working at the universities of Zagreb, Rijeka, Osijek and Split (Croatia), Ulm (Germany) and Graz (Austria). Method. Analysis of the numbers of papers obtained by searching the SCIsearch database of the Institute for Scientific Information (ISI) and MEDLINE. Results. The universities of Osijek, Rijeka and Split, with only 0.42, 0.55 and 0.75 published papers per scientist over a 10-year period respectively,were found to have the lowest scientific output. Although the 1.65 papers published by an average scientist of the University of Zagreb were a significantly higher output compared with the above regional universities, they were still considerably below the production of the University of Ulm (6.6 papers per scientist) and that of Graz (2 papers per scientist). The comparison of the number of papers per 1,000 students gave similar results.. Conclusion. Irrespective of the parameter used for the comparison of scientific development, the three Croatian regional universities were found to lag significantly behind the University of Zagreb. In our opinion, the level of research activities is so dramatically low that it questions further development of these universities. The two main obstacles to an immediate improvement of Croatian science are: (a) a lack of high-quality scientists who could take up the burden of scientific development, and (b) a slow process of the organizational transformation of universities, with an obvious tendency to be devaluated since its very beginning. What Croatian scientific research urgently needs is the introduction of international standards, including the selection of scientists. The new Bill of Science and the National Research Program may be a good foundation for such efforts in the future

Rapid Endosomal Recycling

Peripheral membrane proteins are endocytosed by constitutive processes of membrane invaginations, followed by internalization driven by diverse endocytic machinery available at the cell surface. It is believed that after endocytic uptake, cargo proteins proceed either through the endosomal recycling circuit of the cell or travel toward late endosomes for degradation. In this chapter, we analyzed trafficking of seven cargo molecules (transferrin receptor, fully conformed MHC-I, non-conformed MHC-I, cholera-toxin B subunit, CD44, ICAM1, and G-protein-coupled receptor Rae-1) known to use the distinct endocytic route. For that purpose, we developed the software for multicompartment analysis of intracellular trafficking. We demonstrate that all endocytosed molecules are rapidly recycled and propose that the rapid recycling is a constitutive process that should be considered in the analysis of intracellular trafficking of peripheral membrane proteins

Cytomegaloviruses Exploit Recycling Rab Proteins in the Sequential Establishment of the Assembly Compartment

Cytomegaloviruses (CMV) reorganize membranous system of the cell in order to develop a virion assembly compartment (VAC). The development starts in the early (E) phase of infection with the reorganization of the endosomal system and the Golgi and proceeds to the late phase until newly formed virions are assembled and released. The events in the E phase involve reorganization of the endosomal recycling compartment (ERC) in a series of cellular alterations that are mostly unknown. In this minireview, we discuss the effect of murine CMV infection on Rab proteins, master regulators of membrane trafficking pathways, which in the cascades with their GEFs and GAPs organize the flow of membranes through the ERC. Immunofluorescence analyzes of murine CMV infected cells suggest perturbations of Rab cascades that operate at the ERC. Analysis of cellular transcriptome in the course of both murine and human CMV infection demonstrates the alteration in expression of cellular genes whose products are known to build Rab cascades. These alterations, however, cannot explain perturbations of the ERC. Cellular proteome data available for human CMV infected cells suggests the potential role of RabGAP downregulation at the end of the E phase. However, the very early onset of the ERC alterations in the course of MCMV infection indicates that CMVs exploit Rab cascades to reorganize the ERC, which represents the earliest step in the sequential establishment of the cVAC

Endocytic Trafficking of Cholera Toxin in Balb 3T3 Cells

Endocytosis of the cholera toxin B subunit (CTxB) in various cell lines has shown diversity of entry paths of cell surface bound ligands. The aim of this study was to clarify internalisation mechanism and endosomal trafficking of CTxB in murine fibroblasts (Balb 3T3 cells) and human epithelial cells (HeLa). We have shown that CTxB enters Balb 3T3 cells mainly via cholesterol-dependent endocytic pathway(s), while in HeLa cells clathrin endocytosis plays a major role. Early endosomal acidic gradient is required for CTxB progression towards the Golgi in HeLa cells, whereas a majority of internalised CTxB bypasses early endosomes (EEA1+ compartments) in Balb 3T3 cells. The acidic gradient is also required for exit from the Golgi into the late endosomes and degradation of CTxB in Balb 3T3 cells. Thus, the CTxB trafficking may help in the understanding of non-clathrin endocytic mechanisms and the complexity of late endosomal compartments

Cytomegalovirus immune evasion by perturbation of endosomal trafficking

Cytomegaloviruses (CMVs), members of the herpesvirus family, have evolved a variety of mechanisms to evade the immune response to survive in infected hosts and to establish latent infection. They effectively hide infected cells from the effector mechanisms of adaptive immunity by eliminating cellular proteins (major histocompatibility Class I and Class II molecules) from the cell surface that display viral antigens to CD8 and CD4 T lymphocytes. CMVs also successfully escape recognition and elimination of infected cells by natural killer (NK) cells, effector cells of innate immunity, either by mimicking NK cell inhibitory ligands or by downregulating NK cell-activating ligands. To accomplish these immunoevasion functions, CMVs encode several proteins that function in the biosynthetic pathway by inhibiting the assembly and trafficking of cellular proteins that participate in immune recognition and thereby, block their appearance at the cell surface. However, elimination of these proteins from the cell surface can also be achieved by perturbation of their endosomal route and subsequent relocation from the cell surface into intracellular compartments. Namely, the physiological route of every cellular protein, including immune recognition molecules, is characterized by specific features that determine its residence time at the cell surface. In this review, we summarize the current understanding of endocytic trafficking of immune recognition molecules and perturbations of the endosomal system during infection with CMVs and other members of the herpesvirus family that contribute to their immune evasion mechanism

Cytomegalovirus immune evasion by perturbation of endosomal trafficking

Cytomegaloviruses (CMVs), members of the herpesvirus family, have evolved a variety of mechanisms to evade the immune response to survive in infected hosts and to establish latent infection. They effectively hide infected cells from the effector mechanisms of adaptive immunity by eliminating cellular proteins (major histocompatibility Class I and Class II molecules) from the cell surface that display viral antigens to CD8 and CD4 T lymphocytes. CMVs also successfully escape recognition and elimination of infected cells by natural killer (NK) cells, effector cells of innate immunity, either by mimicking NK cell inhibitory ligands or by downregulating NK cell-activating ligands. To accomplish these immunoevasion functions, CMVs encode several proteins that function in the biosynthetic pathway by inhibiting the assembly and trafficking of cellular proteins that participate in immune recognition and thereby, block their appearance at the cell surface. However, elimination of these proteins from the cell surface can also be achieved by perturbation of their endosomal route and subsequent relocation from the cell surface into intracellular compartments. Namely, the physiological route of every cellular protein, including immune recognition molecules, is characterized by specific features that determine its residence time at the cell surface. In this review, we summarize the current understanding of endocytic trafficking of immune recognition molecules and perturbations of the endosomal system during infection with CMVs and other members of the herpesvirus family that contribute to their immune evasion mechanism