Recognition of l--homomethionine by methionyl-trna synthetase

Living cells commonly employ the 20 canonical amino acids for ribosomal protein synthesis, although a few other amino acids (such as selenocysteine or pyrrolysine) are also employed in rare cases. The natural repertoire of amino acids is therefore rather narrow. This limits the possibilities to engineer non-natural proteins with new properties, usable for therapeutic or industrial purpose. Therefore, a dominant trend in the field of protein engineering is to build up systems for incorporating non-natural amino acids during protein biosynthesis in vivo (reviewed in Xiao and Schultz, 2016). Although this strategy has been successful in several cases, all amino acids used to date were amino acids. Site-specific incorporation of a amino acid in a polypeptide would introduce unprecedented flexibility in the main chain, thereby enlarging the geometric possibilities for protein folding. It has recently been demonstrated, using an in vitro cell-free translation system, that the ribosome is able to efficiently incorporate amino acids at discrete sites in a polypeptide (Fujino et al, 2016). At this stage, a technological issue that needs to be resolved for in vivo synthesis of a protein containing amino acid residues is the design of aminoacyl-tRNA synthetases able to efficiently esterify the desired amino acids onto specific transfer RNAs. A recent study has shown that some E. coli aminoacyl-tRNA synthetases are indeed able to use amino acids as substrates (Melo Czekster et al, 2016). Our final goal is to optimize incorporation of methionine in polypeptides. To this aim, we have first characterized the binding and activation of L--homomethionine by E. coli methionyl-tRNA synthetase. It is demonstrated that activation of the amino acid occurs but at a markedly lower rate than activation of L--methionine. A 1.45 Å crystal structure of methionyl-tRNA synthetase complexed with the amino acid will also be presented. We will discuss how this structure is used for optimizing aminoacylation of tRNA with L--homomethionine. Fujino, T., Goto, Y., Suga, H. and Murakami, H. J Am Chem Soc, 2016, 138, 1962-1969. Melo Czekster, C., Robertson, W. E., Walker, A. S., Soll, D. and Schepartz, A. J Am Chem Soc, 2016, 138, 5194-5197. Cold Spring Harb Perspect Biol, 2016, vol8-9

Pin1 and neurodegeneration: a new player for prion disorders?

Pin1 is a peptidyl-prolyl isomerase that catalyzes the cis/trans conversion of phosphorylated proteins at serine or threonine residues which precede a proline. The peptidyl-prolyl isomerization induces a conformational change of the proteins involved in cell signaling process. Pin1 dysregulation has been associated with some neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Proline-directed phosphorylation is a common regulator of these pathologies and a recent work showed that it is also involved in prion disorders. In fact, prion protein phosphorylation at the Ser-43-Pro motif induces prion protein conversion into a disease-associated form. Furthermore, phosphorylation at Ser-43-Pro has been observed to increase in the cerebral spinal fluid of sporadic Creutzfeldt-Jakob Disease patients. These findings provide new insights into the pathogenesis of prion disorders, suggesting Pin1 as a potential new player in the disease. In this paper, we review the mechanisms underlying Pin1 involvement in the aforementioned neurodegenerative pathologies focusing on the potential role of Pin1 in prion disorders

COPD management as a model for all chronic respiratory conditions : report of the 4th Consensus Conference in Respiratory Medicine

Background: Non-communicable diseases (NCDs) kill 40 million people each year. The management of chronic respiratory NCDs such as chronic obstructive pulmonary disease (COPD) is particularly critical in Italy, where they are widespread and represent a heavy burden on healthcare resources. It is thus important to redefine the role and responsibility of respiratory specialists and their scientific societies, together with that of the whole healthcare system, in order to create a sustainable management of COPD, which could become a model for other chronic respiratory conditions. Methods: These issues were divided into four main topics (Training, Organization, Responsibilities, and Sustainability) and discussed at a Consensus Conference promoted by the Research Center of the Italian Respiratory Society held in Rome, Italy, 3-4 November 2016. Results and conclusions: Regarding training, important inadequacies emerged regarding specialist training - both the duration of practical training courses and teaching about chronic diseases like COPD. A better integration between university and teaching hospitals would improve the quality of specialization. A better organizational integration between hospital and specialists/general practitioners (GPs) in the local community is essential to improve the diagnostic and therapeutic pathways for chronic respiratory patients. Improving the care pathways is the joint responsibility of respiratory specialists, GPs, patients and their caregivers, and the healthcare system. The sustainability of the entire system depends on a better organization of the diagnostic-therapeutic pathways, in which also other stakeholders such as pharmacists and pharmaceutical companies can play an important role

Gabapentin: Clinical Use and Pharmacokinetics in Dogs, Cats, and Horses

Gabapentin is an anticonvulsant drug, which presents an established clinical efficacy in human patients for the management of refractory partial seizures, secondarily generalized tonic-clonic seizures, and for the control of chronic neuropathic pain. Gabapentin was synthesized as a structural analogue of the inhibitory neurotransmitter GABA, with GABA-mimetic effects, able to cross the blood–brain barrier. In veterinary medicine, is extra-label used in combination with other treatments to control seizures when other drugs are no longer effective or become toxic or for neuropathic pain treatment and anxiety. This review aimed to clarify gabapentin use and pharmacokinetic aspects to promote conscious use in dogs, cats, and horses. In dogs, gabapentin was beneficial in the treatment of epilepsy, as well as chronic, neuropathic, and post-operative pain, as well as anxiety. In cats, it showed efficacy in post-ovariohysterectomy-related pain and in anxiety management. In horses, gabapentin has been administered as an analgesic for chronic pain management. In conclusion, when used in combination with other drugs, gabapentin can be considered an interesting therapeutic option for the treatment of neuropathic diseases and analgesia in postoperative and chronic pain. However, despite its beneficial use in different clinical settings, further trials and pharmacokinetic studies are needed for the definition of an effective dosage regimen through proper pharmacokinetic/pharmacodynamic correlation in dogs, cats, and horses

Formazione-Informazione per la sicurezza degli studenti: l\u2019esperienza dell\u2019Universit\ue0 di Trieste in collaborazione con l\u2019INAIL

Biassunto. L'Universit\ue0 di Trieste: in ccillaborazione con l'INAILha attivato un corso multimediale destinato a studenti e borsisti per formarli e informarli sulla sicurezza e i rischi professionali. I programmi sono accessibili on-line e prevedono la compilazione d\uec un questionario di apprendimento e di un certificato d\uec frequenza da consegnare prima di svolgere l'attivit\ue0 a rischio

Regional Citrate Anticoagulation during Coupled Plasma Filtration and Adsorption May Increase Survival in Septic Shock

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Influence of Timing of Initiation and Volume of Processed Plasma on the Outcome of Septic Shock Patients Treated with Coupled Plasma Filtration and Adsorption

The extracorporeal removal of mediators is a rescue strategy for septic shock patients, which is still under investigation. Several techniques are available: coupled plasma filtration and adsorption (CPFA) combines plasma processing with renal replacement therapy