Agent-based approach for cross-subnet communication

Projecte realitzat mitjançant programa de mobilitat. TECHNISCHE UNIVERSITÄT BERLIN. FAKULTÄT IV - ELEKTROTECHNIK UND INFORMATIKThe establishment of point-to-point connections between hosts behind NAT boxes have been always a problem due to the problem with the private IP addresses and NAT rewalls. To solve this problem, there are di erent techniques to make possible that hosts behind NAT boxes can establish a point-to-point connection rounding NAT rewalls and using solutions to exchange their IPs. The goal of this thesis is to present an implementation of a communication protocol which establishes a communication between agents that are behind NAT boxes avoiding all the problems that could occur during the communication, such as duplicated IP addresses or host unreachable errors and introduce to the reader some related work about NAT traversal. There is also in this thesis a little introduction to the existing techniques used to round a NAT rewall and the explanation of why we use NAT boxes even though they sometimes are a problem

SECURING BGP OVER SOFTWARE DEFINED NETWORKS

In this paper use the SDN paradigm to improve the security of BGP based on the Cisco SDN platform, OnePK. The proposed solution has the characteristic that do not need big changes to the network or the devices. A test environment has been created to prove that the feasibility of the solution

Nanomechanics of tip-link cadherins

Hearing and balance rely on the transduction of mechanical stimuli arising from sound waves or head movements into electrochemical signals. This archetypal mechanoelectrical transduction process occurs in the hair-cell stereocilia of the inner ear, which experience continuous oscillations driven by undulations in the endolymph in which they are immersed. The filamentous structures called tip links, formed by an intertwined thread composed of an heterotypic complex of cadherin 23 and protocadherin 15 ectodomain dimers, connect each stereocilium to the tip of the lower sterocilium, and must maintain their integrity against continuous stimulatory deflections. By using single molecule force spectroscopy, here we demonstrate that in contrast to the case of classical cadherins, tip-link cadherins are mechanoresilient structures even at the exceptionally low Ca2+ concentration of the endolymph. We also show that the D101G deafness point mutation in cadherin 23, which affects a Ca2+ coordination site, exhibits an altered mechanical phenotype at the physiological Ca2+ concentration. Our results show a remarkable case of functional adaptation of a protein’s nanomechanics to extremely low Ca2+ concentrations and pave the way to a full understanding of the mechanotransduction mechanism mediated by auditory cadherinsThis work was supported by the BIO2010-22275 grant from the Spanish Ministry of Science and Innovation (MICINN) to M.C.-V

Agent-based approach for cross-subnet communication

Projecte realitzat mitjançant programa de mobilitat. TECHNISCHE UNIVERSITÄT BERLIN. FAKULTÄT IV - ELEKTROTECHNIK UND INFORMATIKThe establishment of point-to-point connections between hosts behind NAT boxes have been always a problem due to the problem with the private IP addresses and NAT rewalls. To solve this problem, there are di erent techniques to make possible that hosts behind NAT boxes can establish a point-to-point connection rounding NAT rewalls and using solutions to exchange their IPs. The goal of this thesis is to present an implementation of a communication protocol which establishes a communication between agents that are behind NAT boxes avoiding all the problems that could occur during the communication, such as duplicated IP addresses or host unreachable errors and introduce to the reader some related work about NAT traversal. There is also in this thesis a little introduction to the existing techniques used to round a NAT rewall and the explanation of why we use NAT boxes even though they sometimes are a problem

SECURING BGP OVER SOFTWARE DEFINED NETWORKS

In this paper use the SDN paradigm to improve the security of BGP based on the Cisco SDN platform, OnePK. The proposed solution has the characteristic that do not need big changes to the network or the devices. A test environment has been created to prove that the feasibility of the solution

Agent-based approach for cross-subnet communication

Projecte realitzat mitjançant programa de mobilitat. TECHNISCHE UNIVERSITÄT BERLIN. FAKULTÄT IV - ELEKTROTECHNIK UND INFORMATIKThe establishment of point-to-point connections between hosts behind NAT boxes have been always a problem due to the problem with the private IP addresses and NAT rewalls. To solve this problem, there are di erent techniques to make possible that hosts behind NAT boxes can establish a point-to-point connection rounding NAT rewalls and using solutions to exchange their IPs. The goal of this thesis is to present an implementation of a communication protocol which establishes a communication between agents that are behind NAT boxes avoiding all the problems that could occur during the communication, such as duplicated IP addresses or host unreachable errors and introduce to the reader some related work about NAT traversal. There is also in this thesis a little introduction to the existing techniques used to round a NAT rewall and the explanation of why we use NAT boxes even though they sometimes are a problem

Expanded Conformations of Monomeric Tau Initiate Its Amyloidogenesis

11 pags., 5 figs.Understanding early amyloidogenesis is key to rationally develop therapeutic strategies. Tau protein forms well-characterized pathological deposits but its aggregation mechanism is still poorly understood. Using single-molecule force spectroscopy based on a mechanical protection strategy, we studied the conformational landscape of the monomeric tau repeat domain (tauRD244-368). We found two sets of conformational states, whose frequency is influenced by mutations and the chemical context. While pathological mutations Δ280K and P301L and a pro-amyloidogenic milieu favored expanded conformations and destabilized local structures, an anti-amyloidogenic environment promoted a compact ensemble, including a conformer whose topology might mask two amyloidogenic segments. Our results reveal that to initiate aggregation, monomeric tau-RD244-368 decreases its polymorphism adopting expanded conformations. This could account for the distinct structures found in vitro and across tauopathies.Spanish Agency for Research (AEI). Grant Numbers: SAF2016-76678-C2-1-R, SAF2016-76678-C2-2-R, BFU2015-70072-RPeer reviewe

Molecular mechanism of the inhibition of TDP-43 amyloidogenesis by QBP1

Transactive Response DNA-Binding Protein of 43 kDa (TDP-43) is an essential human protein implicated in Amyotrophic Lateral Sclerosis (ALS) and common dementias. Its C-terminal disordered region, composed of residues 264–414 includes a hydrophobic segment (residues 320–340), which drives physiological liquid/liquid phase separation and a Q/N-rich segment (residues 341–357), which is essential for pathological amyloid formation. Due to TDP-43's relevance for pathology, identifying inhibitors and characterizing their mechanism of action are important pharmacological goals. The Polyglutamine Binding Peptide 1 (QBP1), whose minimal active core is the octapeptide WGWWPGIF, strongly inhibits the aggregation of polyQ-containing amyloidogenic proteins such as Huntingtin. Rather promiscuous, this inhibitor also blocks the aggregation of other glutamine containing amyloidogenic proteins, but not Aβ, and its mechanism of action remains unknown. Using a series of spectroscopic assays and biochemical tests, we establish that QBP1 binds and inhibits amyloid formation by TDP-43's Q/N-rich region. NMR spectroscopic data evince that the aromatic rings of QBP1 accept hydrogen bonds from the HN groups of the Asn and Gln to block amyloidogenesis. This mechanism of blockage may be general to polyphenol amyloid inhibitors.This study was supported by a Junior Leader Project LCF/BQ/PR19/11700003 (to MMG) from the Caixa Foundation (CID-100010434),and projects SAF2016-76678-C2-1-R (MC-V) and SAF2016-76678-C2-2-R(DVL) from the Spanish Ministry of Economy and Competitivity.NMR experiments were performed in the “Manuel Rico” NMR Laboratory (LMR) of the Spanish National Research Council (CSIC), a node of the Spanish Large-Scale National Facility (ICTSR-LRB)

Divergent CPEB prion-like domains reveal different assembly mechanisms for a generic amyloid-like fold

14 pags., 4 figs.Background: Amyloids are ordered, insoluble protein aggregates, characterized by a cross-β sheet quaternary structure in which molecules in a β-strand conformation are stacked along the filament axis via intermolecular interactions. While amyloids are typically associated with pathological conditions, functional amyloids have also been identified and are present in a wide variety of organisms ranging from bacteria to humans. The cytoplasmic polyadenylation element-binding (CPEB) prion-like protein is an mRNA-binding translation regulator, whose neuronal isoforms undergo activity-dependent aggregation, a process that has emerged as a plausible biochemical substrate for memory maintenance. CPEB aggregation is driven by prion-like domains (PLD) that are divergent in sequence across species, and it remains unknown whether such divergent PLDs follow a similar aggregating assembly pathway. Here, we describe the amyloid-like features of the neuronal Aplysia CPEB (ApCPEB) PLD and compare them to those of the Drosophila ortholog, Orb2 PLD. Results: Using in vitro single-molecule and bulk biophysical methods, we find transient oligomers and mature amyloid-like filaments that suggest similarities in the late stages of the assembly pathway for both ApCPEB and Orb2 PLDs. However, while prior to aggregation the Orb2 PLD monomer remains mainly as a random coil in solution, ApCPEB PLD adopts a diversity of conformations comprising α-helical structures that evolve to coiled-coil species, indicating structural differences at the beginning of their amyloid assembly pathways. Conclusion: Our results indicate that divergent PLDs of CPEB proteins from different species retain the ability to form a generic amyloid-like fold through different assembly mechanisms.The work was funded by two joint grants from the Ministry of Economy and Competitiveness to MCV (SAF2013-49179-C2-1-R and SAF2016-76678-C2-1-R) and DVL (SAF2013-49179-C2-2-R and SAF2016-76678-C2-2-R) and grants of the Ministry of Economy and Science (BFU2015-70072-R) and the CIBER de Enfermedades Respiratorias (CIBERES; ISCIII) to MM

Molecular basis of Orb2 amyloidogenesis and blockade of memory consolidation

Amyloids are ordered protein aggregates that are typically associated with neurodegenerative diseases and cognitive impairment. By contrast, the amyloid-like state of the neuronal RNA binding protein Orb2 in Drosophila was recently implicated in memory consolidation, but it remains unclear what features of this functional amyloid-like protein give rise to such diametrically opposed behaviour. Here, using an array of biophysical, cell biological and behavioural assays we have characterized the structural features of Orb2 from the monomer to the amyloid state. Surprisingly, we find that Orb2 shares many structural traits with pathological amyloids, including the intermediate toxic oligomeric species, which can be sequestered in vivo in hetero-oligomers by pathological amyloids. However, unlike pathological amyloids, Orb2 rapidly forms amyloids and its toxic intermediates are extremely transient, indicating that kinetic parameters differentiate this functional amyloid from pathological amyloids. We also observed that a well-known anti-amyloidogenic peptide interferes with long-term memory in Drosophila. These results provide structural insights into how the amyloid-like state of the Orb2 protein can stabilize memory and be nontoxic. They also provide insight into how amyloid-based diseases may affect memory processes.This research was supported by funds from SAF2013-49179-C2-1-R JPND_CD_FP-688- 059 (AC14/00037 ISCIII) to MCV, SIMR to KS, SAF2013-49179-C2-2-R JPND_CD_FP-688-059 (AC14/00037 ISCIII) to DVL, BFU2012-36825, S2011/BMD-2457 (Comunidad de Madrid)Peer Reviewe