Evaluation of Feasibility and Impact of Attacks against the 6top Protocol in 6TiSCH Networks

The 6TiSCH architecture has been gaining attraction as a promising solution to ensure reliability and security for communication in applications for the Industrial Internet of Things (IIoT). While many different aspects of the architecture have been investigated in literature, an in-depth analysis of the security features included in its design is still missing. In this paper, we assess the security vulnerabilities of the 6top protocol, a core component of the 6TiSCH architecture for enabling network nodes to negotiate communication resources. Our analysis highlights two possible attacks against the 6top protocol that can impair network performance and reliability in a significant manner. To prove the feasibility of the attacks in practice, we implemented both of them on the Contiki-NG Operating System and tested their effectiveness on a simple deployment with three Zolertia RE-Mote sensor nodes. Also, we carried out a set of simulations using Cooja in order to assess their impact on larger networks. Our results show that both attacks reduce reliability in the overall network and increase energy consumption of the network nodes

Anisotropy and NMR spectroscopy

Abstract: In this paper, different aspects concerning anisotropy in Nuclear Magnetic Resonance (NMR) spectroscopy have been reviewed. In particular, the relevant theory has been presented, showing how anisotropy stems from the dependence of internal nuclear spin interactions on the molecular orientation with respect to the external magnetic field direction. The consequences of anisotropy in the use of NMR spectroscopy have been critically discussed: on one side, the availability of very detailed structural and dynamic information, and on the other side, the loss of spectral resolution. The experiments used to measure the anisotropic properties in solid and soft materials, where, in contrast to liquids, such properties are not averaged out by the molecular tumbling, have been described. Such experiments can be based either on static low-resolution techniques or on one- and two-dimensional pulse sequences exploiting Magic Angle Spinning (MAS). Examples of applications of NMR spectroscopy have been shown, which exploit anisotropy to obtain important physico-chemical information on several categories of systems, including pharmaceuticals, inorganic materials, polymers, liquid crystals, and self-assembling amphiphiles in water. Solid-state NMR spectroscopy can be considered, nowadays, one of the most powerful characterization techniques for all kinds of solid, either amorphous or crystalline, and semi-solid systems for the obtainment of both structural and dynamic properties on a molecular and supra-molecular scale. Graphic abstract: [Figure not available: see fulltext.

Pharmacological Comparative Characterization of REL-1017 (Esmethadone-HCl) and Other NMDAR Channel Blockers in Human Heterodimeric N-Methyl-D-Aspartate Receptors

Excessive Ca2+ currents via N-methyl-D-aspartate receptors (NMDARs) have been implicated in many disorders. Uncompetitive NMDAR channel blockers are an emerging class of drugs in clinical use for major depressive disorder (MDD) and other neuropsychiatric diseases. The pharmacological characterization of uncompetitive NMDAR blockers in clinical use may improve our understanding of NMDAR function in physiology and pathology. REL-1017 (esmethadone-HCl), a novel uncompetitive NMDAR channel blocker in Phase 3 trials for the treatment of MDD, was characterized together with dextromethorphan, memantine, (±)-ketamine, and MK-801 in cell lines over-expressing NMDAR subtypes using fluorometric imaging plate reader (FLIPR), automated patch-clamp, and manual patch-clamp electrophysiology. In the absence of Mg2+, NMDAR subtypes NR1-2D were most sensitive to low, sub-μM glutamate concentrations in FLIPR experiments. FLIPR Ca2+ determination demonstrated low μM affinity of REL-1017 at NMDARs with minimal subtype preference. In automated and manual patch-clamp electrophysiological experiments, REL-1017 exhibited preference for the NR1-2D NMDAR subtype in the presence of 1 mM Mg2+ and 1 μM L-glutamate. Tau off and trapping characteristics were similar for (±)-ketamine and REL-1017. Results of radioligand binding assays in rat cortical neurons correlated with the estimated affinities obtained in FLIPR assays and in automated and manual patch-clamp assays. In silico studies of NMDARs in closed and open conformation indicate that REL-1017 has a higher preference for docking and undocking the open-channel conformation compared to ketamine. In conclusion, the pharmacological characteristics of REL-1017 at NMDARs, including relatively low affinity at the NMDAR, NR1-2D subtype preference in the presence of 1 mM Mg2+, tau off and degree of trapping similar to (±)-ketamine, and preferential docking and undocking of the open NMDAR, could all be important variables for understanding the rapid-onset antidepressant effects of REL-1017 without psychotomimetic side effects

Mechanisms Used for Genomic Proliferation by Thermophilic Group II Introns

Studies of mobile group II introns from a thermophilic cyanobacterium reveal how these introns proliferate within genomes and might explain the origin of introns and retroelements in higher organisms

The Retrohoming of Linear Group II Intron RNAs in Drosophila melanogaster Occurs by Both DNA Ligase 4–Dependent and –Independent Mechanisms

Mobile group II introns are bacterial retrotransposons that are thought to have invaded early eukaryotes and evolved into introns and retroelements in higher organisms. In bacteria, group II introns typically retrohome via full reverse splicing of an excised intron lariat RNA into a DNA site, where it is reverse transcribed by the intron-encoded protein. Recently, we showed that linear group II intron RNAs, which can result from hydrolytic splicing or debranching of lariat RNAs, can retrohome in eukaryotes by performing only the first step of reverse splicing, ligating their 3′ end to the downstream DNA exon. Reverse transcription then yields an intron cDNA, whose free end is linked to the upstream DNA exon by an error-prone process that yields junctions similar to those formed by non-homologous end joining (NHEJ). Here, by using Drosophila melanogaster NHEJ mutants, we show that linear intron RNA retrohoming occurs by major Lig4-dependent and minor Lig4-independent mechanisms, which appear to be related to classical and alternate NHEJ, respectively. The DNA repair polymerase θ plays a crucial role in both pathways. Surprisingly, however, mutations in Ku70, which functions in capping chromosome ends during NHEJ, have only moderate, possibly indirect effects, suggesting that both Lig4 and the alternate end-joining ligase act in some retrohoming events independently of Ku. Another potential Lig4-independent mechanism, reverse transcriptase template switching from the intron RNA to the upstream exon DNA, occurs in vitro, but gives junctions differing from the majority in vivo. Our results show that group II introns can utilize cellular NHEJ enzymes for retromobility in higher organisms, possibly exploiting mechanisms that contribute to retrotransposition and mitigate DNA damage by resident retrotransposons. Additionally, our results reveal novel activities of group II intron reverse transcriptases, with implications for retrohoming mechanisms and potential biotechnological applications

Learning to live together: mutualism between self-splicing introns and their hosts

Group I and II introns can be considered as molecular parasites that interrupt protein-coding and structural RNA genes in all domains of life. They function as self-splicing ribozymes and thereby limit the phenotypic costs associated with disruption of a host gene while they act as mobile DNA elements to promote their spread within and between genomes. Once considered purely selfish DNA elements, they now seem, in the light of recent work on the molecular mechanisms regulating bacterial and phage group I and II intron dynamics, to show evidence of co-evolution with their hosts. These previously underappreciated relationships serve the co-evolving entities particularly well in times of environmental stress