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Università della Svizzera italiana

Consensus protocols exploiting network programmability

Dang, Huynh Tu ; Soulé, Robert (Dir.) ; Pedone, Fernando (Codir.)

Thèse de doctorat : Università della Svizzera italiana, 2019 ; 2019INFO003.

Services rely on replication mechanisms to be available at all time. The service demanding high availability is replicated on a set of machines called replicas. To maintain the consistency of replicas, a consensus protocol such as Paxos or Raft is used to synchronize the replicas' state. As a result, failures of a minority of replicas will not affect the service as other non-faulty replicas...

Università della Svizzera italiana

How viruses hijack the ERAD tuning machinery

Noack, Julia ; Bernasconi, Riccardo ; Molinari, Maurizio

In: Journal of virology, 2014, vol. 88, no. 18, p. 10272-10275

An essential step during the intracellular life cycle of many positive-strand RNA viruses is the rearrangement of host cell membranes to generate membrane-bound replication platforms. For example, Nidovirales and Flaviviridae subvert the membrane of the endoplasmic reticulum (ER) for their replication. However, the absence of conventional ER and secretory pathway markers in virus-induced...

Università della Svizzera italiana

Immunological consequences of intragenus conservation of Mycobacterium tuberculosis T-cell epitopes

Lindestam Arlehamn, Cecilia S. ; Paul, Sinu ; Mele, Federico ; Huang, Charlie ; Greenbaum, Jason A. ; Vita, Randi ; Sidney, John ; Peters, Bjoern ; Sallusto, Federica ; Sette, Alessandro

In: Proceedings of the national academy of sciences of the United States of America, 2015, vol. 112, no. 2, p. E147-E155

A previous unbiased genome-wide analysis of CD4 Mycobacterium tuberculosis (MTB) recognition using peripheral blood mononuclear cells from individuals with latent MTB infection (LTBI) or nonexposed healthy controls (HCs) revealed that certain MTB sequences were unexpectedly recognized by HCs. In the present study, it was found that, based on their pattern of reactivity, epitopes could be...

Università della Svizzera italiana

Division of labor among oxidoreductases : TMX1 preferentially acts on transmembrane polypeptides

Brambilla Pisoni, Giorgia ; Ruddock, Lloyd W. ; Bulleid, Neil ; Molinari, Maurizio

In: Molecular biology of the cell, 2015, vol. 26, no. 19, p. 3373-3556

The endoplasmic reticulum (ER) is the site of maturation for secretory and membrane proteins in eukaryotic cells. The lumen of the mammalian ER contains >20 members of the protein disulfide isomerase (PDI) superfamily, which ensure formation of the correct set of intramolecular and intermolecular disulfide bonds as crucial, rate-limiting reactions of the protein folding process. Components of...

Università della Svizzera italiana

A novel UGGT1 and p97-dependent checkpoint for native ectodomains with ionizable intramembrane residue

Merulla, Jessica ; Tatiana Soldà ; Maurizio Molinari

In: Molecular biology of the cell, 2015, vol. 26, no. 8, p. 1413-1574

Only native polypeptides are released from the endoplasmic reticulum (ER) to be transported at the site of activity. Persistently misfolded proteins are retained and eventually selected for ER-associated degradation (ERAD). The paradox of a structure- based protein quality control is that functional polypeptides may be destroyed if they are architecturally unfit. This has health-threatening...

Università della Svizzera italiana

Influenza hemagglutinin membrane anchor

Benton, Donald J. ; Nans, Andrea ; Calder, Lesley J. ; Turner, Jack ; Neu, Ursula ; Lin, Yi Pu ; Ketelaars, Esther ; Kallewaard, Nicole L. ; Corti, Davide ; Lanzavecchia, Antonio ; Gamblin, Steven J. ; Rosenthal, Peter B. ; Skehel, John J.

In: Proceedings of the national academy of sciences of the United States of America, 2018, vol. 115, no. 40, p. 10112-10117

Viruses with membranes fuse them with cellular membranes, to transfer their genomes into cells at the beginning of infection. For Influenza virus, the membrane glycoprotein involved in fusion is the hemagglutinin (HA), the 3D structure of which is known from X-ray crystallographic studies. The soluble ectodomain fragments used in these studies lacked the “membrane anchor” portion of the...

Università della Svizzera italiana

Particle conformation regulates antibody access to a conserved GII.4 norovirus blockade epitope

Lindesmith, Lisa C. ; Donaldson, Eric F. ; Beltramello, Martina ; Pintus, Stefania ; Corti, Davide ; Swanstrom, Jesica ; Debbink, Kari ; Jones, Taylor A. ; Lanzavecchia, Antonio ; Baric, Ralph S.

In: Journal of virology, 2014, vol. 88, no. 16, p. 8826-8842

GII.4 noroviruses (NoVs) are the primary cause of epidemic viral acute gastroenteritis. One primary obstacle to successful NoV vaccination is the extensive degree of antigenic diversity among strains. The major capsid protein of GII.4 strains is evolving rapidly, resulting in the emergence of new strains with altered blockade epitopes. In addition to characterizing these evolving blockade...

Università della Svizzera italiana

Human IL-3/GM-CSF knock-in mice support human alveolar macrophage development and human immune responses in the lung

Willinger, Tim ; Rongvaux, Anthony ; Takizawa, Hitoshi ; Yancopoulos, George D. ; Valenzuela, David M. ; Murphy, Andrew J. ; Auerbach, Wojtek ; Eynon, Elizabeth E. ; Stevens, Sean ; Manz, Markus G. ; Flavell, Richard A.

In: Proceedings of the national academy of sciences of the United States of America, 2011, vol. 108, no. 6, p. 2390-2395

Mice with a functional human immune system have the potential to allow in vivo studies of human infectious diseases and to enable vaccine testing. To this end, mice need to fully support the development of human immune cells, allow infection with human pathogens, and be capable of mounting effective human immune responses. A major limitation of humanized mice is the poor development and...

Università della Svizzera italiana

Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo

Rongvaux, Anthony ; Willinger, Tim ; Takizawa, Hitoshi ; Rathinam, Chozhavendan ; Auerbach, Wojtek ; Murphy, Andrew J. ; Valenzuela, David M. ; Yancopoulos, George D. ; Eynon, Elizabeth E. ; Stevens, Sean ; Manz, Markus G. ; Flavell, Richard A.

In: Proceedings of the national academy of sciences of the United States of America, 2011, vol. 108, no. 6, p. 2378-2383

Hematopoietic stem cells (HSCs) both self-renew and give rise to all blood cells for the lifetime of an individual. Xenogeneic mouse models are broadly used to study human hematopoietic stem and progenitor cell biology in vivo. However, maintenance, differentiation, and function of human hematopoietic cells are suboptimal in these hosts. Thrombopoietin (TPO) has been demonstrated as a crucial...

Università della Svizzera italiana

Mitochondrial dysfunction induced by a SH2 domain-targeting STAT3 inhibitor leads to metabolic synthetic lethality in cancer cells

Genini, Davide ; Brambilla, Lara ; Laurini, Erik ; Merulla, Jessica ; Civenni, Gianluca ; Pandit, Shusil ; D'Antuono, Rocco ; Perez, Laurent ; Levy, David E. ; Pricl, Sabrina ; Carbone, Giuseppina M. ; Catapano, Carlo V.

In: Proceedings of the national academy of sciences of the United States of America, 2017, vol. 114, no. 25, p. E4924-E4933

In addition to its canonical role in nuclear transcription, signal transducer and activator of transcription 3 (STAT3) is emerging as an important regulator of mitochondrial function. Here, we demonstrate that a novel inhibitor that binds with high affinity to the STAT3 SH2 domain triggers a complex cascade of events initiated by interference with mitochondrial STAT3 (mSTAT3). The...