INFLUENZA VIRUS INFECTIONS: CLINICAL UPDATE, MOLECULAR BIOLOGY, AND THERAPEUTIC OPTIONS

Influenza is an ancient and deadly disease which has sickened and killed millions of people in local epidemics and global pandemics. Nowadays, it is common knowledge that influenza is a highly infectious viral illness, but before the discovery of viruses the etiological factor of influenza was not known and, therefore, we had to relay solely on the clinical picture characterized by a sudden onset of high fever, cough, headache, muscle and joint pain, unwell feeling, sore throat, and runny nose. These symptoms were clearly described by Hippocrates roughly 2400 years ago, but historical data on influenza were of difficult interpretation, since these symptoms can be similar to those of other respiratory diseases, therefore not distinctive enough. The word Influenza originated in the 15th century from the Italian language, meaning “influence” since the disease was ascribed to unfavorable astrological influences. A different origin could be the word “influsso” for describing the sweating characteristic of the illness or meaning “influence of the cold.” It was not until 1703 when J. Hugger’s thesis submitted at the University of Edinburgh and named “De Catarrho epidemio, vel Influenza, prout in India occidentali sese ostendit” that the Englishspoken world directly associated “influenza” with the disease and its symptoms. After that the name influenza and its shorthand “flu” came into more general use.1 The influenza virus was first isolated from pigs in 1930 by Shope and Lewis.2 This seminal discovery was followed by the isolation in ferrets of influenza A virus by Smith, Andrewes, and Laidlaw.3 In 1936, Burnet demonstrated that influenza virus could be grown in chicken embryonated eggs,4 opening the path for the study of the characteristics of the virus. It is estimated that influenza virus infects every year 5–10% of the adult population worldwide and 20–30% of the children. Even though most patients recover from flu symptoms within a short periodand without serious sequelae, the estimates indicate from 3–5 million cases of serious illness and over 250,000 deaths per year. Therefore, due to its medical importance, influenza viruses have been the focus of extensive research to decipher the molecular mechanisms that dominate cell invasion and pathogenesis

INFLUENZA VIRUS INFECTIONS: CLINICAL UPDATE, MOLECULAR BIOLOGY, AND THERAPEUTIC OPTIONS

Influenza is an ancient and deadly disease which has sickened and killed millions of people in local epidemics and global pandemics. Nowadays, it is common knowledge that influenza is a highly infectious viral illness, but before the discovery of viruses the etiological factor of influenza was not known and, therefore, we had to relay solely on the clinical picture characterized by a sudden onset of high fever, cough, headache, muscle and joint pain, unwell feeling, sore throat, and runny nose. These symptoms were clearly described by Hippocrates roughly 2400 years ago, but historical data on influenza were of difficult interpretation, since these symptoms can be similar to those of other respiratory diseases, therefore not distinctive enough. The word Influenza originated in the 15th century from the Italian language, meaning “influence” since the disease was ascribed to unfavorable astrological influences. A different origin could be the word “influsso” for describing the sweating characteristic of the illness or meaning “influence of the cold.” It was not until 1703 when J. Hugger’s thesis submitted at the University of Edinburgh and named “De Catarrho epidemio, vel Influenza, prout in India occidentali sese ostendit” that the Englishspoken world directly associated “influenza” with the disease and its symptoms. After that the name influenza and its shorthand “flu” came into more general use.1 The influenza virus was first isolated from pigs in 1930 by Shope and Lewis.2 This seminal discovery was followed by the isolation in ferrets of influenza A virus by Smith, Andrewes, and Laidlaw.3 In 1936, Burnet demonstrated that influenza virus could be grown in chicken embryonated eggs,4 opening the path for the study of the characteristics of the virus. It is estimated that influenza virus infects every year 5–10% of the adult population worldwide and 20–30% of the children. Even though most patients recover from flu symptoms within a short periodand without serious sequelae, the estimates indicate from 3–5 million cases of serious illness and over 250,000 deaths per year. Therefore, due to its medical importance, influenza viruses have been the focus of extensive research to decipher the molecular mechanisms that dominate cell invasion and pathogenesis

Microbe-host interactions: structure and role of Gram-negative bacterial porins.

Gram negative bacteria have evolved many mechanisms of attaching to and invading host epithelial and immune cells. In particular, many outer membrane proteins (OMPs) are involved in this initial interaction between the pathogen and their host. The outer membrane (OM) of Gram-negative bacteria performs the crucial role of providing an extra layer of protection to the organism without compromising the exchange of material required for sustaining life. The OM, therefore, represents a sophisticated macromolecular assembly,whose complexity has yet to be fully elucidated.. This review will summarize the structural information available for porins, a class of OMP, and highlight their role in bacterial pathogenesis. The functional role of porins in microbe-host interactions during various bacterial infections has emerged only during the last few decades, and their interaction with a variety of host tissues for adhesion to and invasion of the cell and for evasion of host-defense mechanisms have placed bacterial porins at the forefront of research in bacterial pathogenesis. This review will discuss the role that porins play in activating immunological responses, in inducing signaling pathways and their influence on antibiotic resistance mechanisms that involve modifications of the properties of the OM lipid barrier

Membrane association of Rac and E-cadherin in FRT thyroid epithelial cells.

We are interested in determining the molecular mechanism by which Rac affects the expression of the polarized phenotype in FRT thyroid epithelial cells. To this aim an inducible, constitutively-active form of Rac, ER-Rac(QL), and the inducible, dominant-negative ER-Rac(N17) were stably expressed in FRT cells. By immunofluorescence analysis and cell fractionation we determined that upon tamoxifen treatment of FRT clones expressing ER-Rac(QL), the protein moves from the cytosol to the plasma membrane. The same is true for the dominant-negative ER-Rac(N17) after tamoxifen treatment. The bulk of endogenous Rac is also localized on the plasma membrane of wild-type FRT cells. Treatment with the specific Rac inhibitor NSC23766, removes endogenous Rac from the plasma membrane. Strikingly, E-cadherin is correspondingly removed from the membrane, likely by endocytosis. Chelation of calcium in the culture medium, in a Ca++ switch assay, also causes internalization of E-cadherin from the plasma membrane and the partial removal of Rac. Intracellular E-cadherin and Rac do not colocalize. The coordinate regulation of the association of both proteins to the plasma membrane is under investigation

A constitutively active Rac impairs the acquisition of epithelial cell polarity.

We demonstrated that treatment of FRT thyroid epithelial cells with a Rac-specific inhibitor causes an impairment in the acquisition of polarity. FRT-β8i cells, in which the signal transduction from the β1A integrin is impaired, manifest a similar defect. We tested here the hypothesis that an active Rac might correct the FRT-β8i polarity defect. FRT-β8i cells that stably expressed an inducible, constitutively active Rac, ER-Rac(QL), were obtained. Upon tamoxifen treatment the ER-Rac(QL) protein became active, localized at the plasma membrane and in confluent cells it was mostly found on the lateral plasmamembrane, at sites of cell-cell contact. In these cultured cells cytokinesis was progressively impaired. Furthermore, activation of ER-Rac(QL) interfered with the acquisition of transepithelial resistance by confluent monolayers on filters, impaired cyst formation by cells in suspension culture and reduced the wound healing efficiency in a scratch test. Similar results were obtained with wild-type FRT cells expressing the same ER-Rac(QL). We conclude that a constitutively active Rac does not promote, but rather hampers, the acquisition of cell polarity in epithelial cells

Antimicrobial activity of bovine lactoferrin-derived peptides

Antimicrobial peptides, such as bovine lactoferrin (bLF), are produced by a wide variety of organisms. AMPs represent a first line defence against invading microbes and are found in large quantity in several secretory fluids [1] . They are relatively short, amphiphilic and positively charged. bLF is an 80- kDa iron-binding, multifunctional cationic glycoprotein of the transferrin family. This protein is active against a widespread range of microbiological organisms: bacteria, viruses, fungi and parasites [2,3,4]. In order to obtain novel active peptides from bLF, several approaches have been used. Two novel active peptides have been identified in our study. In agreement with the not disclosure agreement for the pending patent N°102015000044047*, we are not allowed to report the sequences in the abstract. These peptides, named respectively KFp and LKp, were synthesized using the standard solid-phase- 9-fluorenylmethoxycarbonyl (Fmoc) method. Antibacterial activity of KFp and LKp was analyzed by minimal inhibitory concentration (MIC) using the broth microdilution method outlined by the Clinical and Laboratory StandardsInstitute (CLSI) on two bacteria strains: Escherichia coli ATCC 11229 and Staphylococcus aureus ATCC 6538. Likewise, the antiviral activity was performed on HSV-1using a co-treatment assay. Moreover, their cytotoxicity activity was evaluated by the MTT assay.According to the study conducted, these novel peptides show a marked broad-spectrum antimicrobial and antiviral activity with a low toxicity. This can be a favorable prerequisite for the developing and for the use of these peptides in vivo, as additional therapeutic agents and/or as alternative to the conventional antibiotics

I primi 50 anni dell'Ordine Professionale dei geologi Italiani. Almanacco tra storia, curiosità e cronaca. I parte.

Quello illustrato in queto volume, senza trattare la pretesa di trattare con rigore scientifico la storia della geologia italiana, è il racconto di mezzo secolo di attività legate ai geologi ed al loro ordine, a partire da quel lontano 3 febbraio 1963 in cui lo Stato definì, attraverso la Legge n. 112, i criteri per esercitare la professione di geologo, inserandola nel nobile proscenio di quelle regolamentate. A distanza di 50 anni abbiamo consolidato la consapevolezza di questo ruolo e ne sentiamo sempre più la responsabilità. E' il segno della nostra identità di geologi, un valore condiviso di cui andare fieri e su cui costruire il nostro futuro, come persone e come classe professionale

I primi 50 anni dell’ordine Professionale dei geologi Italiani. Almanacco tra storia, curiosità e cronaca.

Quello illustrato in queto volume, senza trattare la pretesa di trattare con rigore scientifico la storia della geologia italiana, è il racconto di mezzo secolo di attività legate ai geologi ed al loro ordine, a partire da quel lontano 3 febbraio 1963 in cui lo Stato definì, attraverso la Legge n. 112, i criteri per esercitare la professione di geologo, inserandola nel nobile proscenio di quelle regolamentate. A distanza di 50 anni abbiamo consolidato la consapevolezza di questo ruolo e ne sentiamo sempre più la responsabilità. E' il segno della nostra identità di geologi, un valore condiviso di cui andare fieri e su cui costruire il nostro futuro, come persone e come classe professionale