Adaptive Parameters for LoRa-Based Networks Physical-Layer.

Sub-GHz communication provides long-range coverage with low power consumption and reduced deployment cost. LoRa (Long-Range) has emerged, among existing LPWAN (Low Power Wide Area Networks) technologies, as a promising physical layer alternative to provide ubiquitous connectivity to outdoor IoT devices. LoRa modulation technology supports adapting transmissions based on parameters such as carrier frequency, channel bandwidth, spreading factor, and code rate. In this paper, we propose SlidingChange, a novel cognitive mechanism to support the dynamic analysis and adjustment of LoRa network performance parameters. The proposed mechanism uses a sliding window to smooth out short-term variations and reduce unnecessary network re-configurations. To validate our proposal, we conducted an experimental study to evaluate the performance concerning the Signal-to-Noise Ratio (SNR) parameter of our SlidingChange against InstantChange, an intuitive mechanism that considers immediate performance measurements (parameters) for re-configuring the network. The SlidingChange is compared with LR-ADR too, a state-of-the-art-related technique based on simple linear regression. The experimental results obtained from a testbed scenario demonstrated that the InstanChange mechanism improved the SNR by 4.6%. When using the SlidingChange mechanism, the SNR was around 37%, while the network reconfiguration rate was reduced by approximately 16%.

Alpha-synuclein in Parkinson's disease: a villain or tragic hero? A critical view of the formation of α-synuclein aggregates induced by dopamine metabolites and viral infection.

INTRODUCTION: Since the discovery of the presynaptic protein α-synuclein (aSyn) as a central player in Parkinson's disease (PD), several key questions on the function of the protein in neurodegeneration processes remain unclear, including: is there a synergy between dopamine metabolism and the formation of toxic aSyn species in neurons? What is the role of aSyn in the immunological system? AREAS COVERED: Herein, the authors revisit the intricate pathways related to dopamine metabolism and how it impacts on aSyn aggregation/function. Additionally, they discuss the importance of aSyn in the immune response to viral infections as well as the current findings on the possible protective role of certain virus vaccines against PD and other neuropathologies. EXPERT OPINION: The physiological function of aSyn seems to cover different pathways, such as immune response against infections and a neuroprotective role, besides the already-established regulation of synaptic vesicle trafficking. Clinical studies with monoclonal antibodies against aSyn aggregates have shown disappointing results in patients with early-stage PD. Alternatively, we could consider, as immunological target, specific neurotoxic oligomers of aSyn formed in the presence of dopamine metabolites, such as DOPAL. Nevertheless, the crucial question remains as to whether removing these protein deposits will affect the clinical course of the disease.

Drone Swarms as Networked Control Systems by Integration of Networking and Computing.

The study of multi-agent systems such as drone swarms has been intensified due to their cooperative behavior. Nonetheless, automating the control of a swarm is challenging as each drone operates under fluctuating wireless, networking and environment constraints. To tackle these challenges, we consider drone swarms as Networked Control Systems (NCS), where the control of the overall system is done enclosed within a wireless communication network. This is based on a tight interconnection between the networking and computational systems, aiming to efficiently support the basic control functionality, namely data collection and exchanging, decision-making, and the distribution of actuation commands. Based on a literature analysis, we do not find revision papers about design of drone swarms as NCS. In this review, we introduce an overview of how to develop self-organized drone swarms as NCS via the integration of a networking system and a computational system. In this sense, we describe the properties of the proposed components of a drone swarm as an NCS in terms of networking and computational systems. We also analyze their integration to increase the performance of a drone swarm. Finally, we identify a potential design choice, and a set of open research challenges for the integration of network and computing in a drone swarm as an NCS.

Hybrid Routing, Modulation, Spectrum and Core Allocation Based on Mapping Scheme.

With the persistently growing popularity of internet traffic, telecom operators are forced to provide high-capacity, cost-efficient, and performance-adaptive connectivity solutions to fulfill the requirements and increase their returns. However, optical networks that make up the core of the Internet gradually reached physical transmission limits. In an attempt to provide new solutions emerged, the Space-Division Multiplexing Elastic Optical Network emerged as one of the best ways to deal with the network depletion. However, it is necessary to establish lightpaths using routing, modulation, spectrum, and core allocation (RMSCA) algorithms to establish connections in these networks. This article proposes a crosstalk-aware RMSCA algorithm that uses a multi-path and mapping scheme for improving resource allocation. The results show that the proposed algorithm decreases the blocking ratio by up to four orders of magnitude compared with other RMSCA algorithms in the literature.

LoRaWAN Gateway Placement Model for Dynamic Internet of Things Scenarios.

Extended Range Wide Area Network (LoRaWAN) has recently gained a lot of attention from the industrial and research community for dynamic Internet of Things (IoT) applications. IoT devices broadcast messages for neighbor gateways that deliver the message to the application server through an IP network. Hence, it is required to deploy LoRaWAN gateways, i.e., network planning, and optimization, in an environment while considering Operational Expenditure (OPEX) and Capital Expenditure (CAPEX) along with Quality of Service (QoS) requirements. In this article, we introduced a LoRaWAN gateway placement model for dynamic IoT applications called DPLACE. It divides the IoT devices into groups with some degree of similarity between them to allow for the placement of LoRaWAN gateways that can serve these devices in the best possible way. Specifically, DPLACE computes the number of LoRaWAN gateways based on the Gap statistics method. Afterward, DPLACE uses K-Means and Fuzzy C-means algorithms to calculate the LoRaWAN gateway placement. The simulations' results proved the benefits of DPLACE compared to state-of-the-art LoRaWAN gateway placement models in terms of OPEX, CAPEX, and QoS.

Data Improvement Model Based on ECG Biometric for User Authentication and Identification.

The rapid spread of wearable technologies has motivated the collection of a variety of signals, such as pulse rate, electrocardiogram (ECG), electroencephalogram (EEG), and others. As those devices are used to do so many tasks and store a significant amount of personal data, the concern of how our data can be exposed starts to gain attention as the wearable devices can become an attack vector or a security breach. In this context, biometric also has expanded its use to meet new security requirements of authentication demanded by online applications, and it has been used in identification systems by a large number of people. Existing works on ECG for user authentication do not consider a population size close to a real application. Finding real data that has a big number of people ECG's data is a challenge. This work investigates a set of steps that can improve the results when working with a higher number of target classes in a biometric identification scenario. These steps, such as increasing the number of examples, removing outliers, and including a few additional features, are proven to increase the performance in a large data set. We propose a data improvement model for ECG biometric identification (user identification based on electrocardiogram-DETECT), which improves the performance of the biometric system considering a greater number of subjects, which is closer to a security system in the real world. The DETECT model increases precision from 78% to 92% within 1500 subjects, and from 90% to 95% within 100 subjects. Moreover, good False Rejection Rate (i.e., 0.064003) and False Acceptance Rate (i.e., 0.000033) were demonstrated. We designed our proposed method over PhysioNet Computing in Cardiology 2018 database.

A multi-tier fog content orchestrator mechanism with quality of experience support.

Video-on-Demand (VoD) services create a demand for content orchestrator mechanisms to support Quality of Experience (QoE). Fog computing brings benefits for enhancing the QoE for VoD services by caching the content closer to the user in a multi-tier fog architecture, considering their available resources to improve QoE. In this context, it is mandatory to consider network, fog node, and user metrics to choose an appropriate fog node to distribute videos with QoE support properly. In this article, we introduce a content orchestrator mechanism, called of Fog4Video, which chooses an appropriate fog node to download video content. The mechanism considers the available bandwidth, delay, and cost, besides the QoE metrics for VoD, namely number of stalls and stalls duration, to deploy VoD services in the opportune fog node. Decision-making acknowledges periodical reports of QoE from the clients to assess the video streaming from each fog node. These values serve as inputs for a real-time Analytic Hierarchy Process method to compute the influence factor for each parameter and compute the QoE improvement potential of the fog node. Fog4Video is executed in fog nodes organized in multiple tiers, having different characteristics to provide VoD services. Simulation results demonstrate that Fog4Video transmits adapted videos with 30% higher QoE and reduced monetary cost up to 24% than other content request mechanisms.

Cluster-Based Control Plane Messages Management in Software-Defined Flying Ad-Hoc Network.

Collaboration between multiple Unmanned Aerial Vehicles (UAVs) to establish a Flying Ad-hoc Network (FANET) is a growing trend since future applications claim for more autonomous and rapidly deployable systems. In this context, Software-Defined Networking FANET (SDN-FANET ) separates the control and data plane and provides network programmability, which considers a centralized controller to perform all FANET control functions based on global UAV context information, such as UAV positions, movement trajectories, residual energy, and others. However, control message dissemination in an SDN-FANET with low overhead and high performance is not a trivial task due to FANET particular characteristics, i.e., high mobility, failures in UAV to UAV communication, and short communication range. With this in mind, it is essential to predict UAV information for control message dissemination as well as consider hierarchical network architecture, reducing bandwidth consumption and signaling overhead. In this article, we present a Cluster-bAsed control Plane messages management in sOftware-defined flying ad-hoc NEtwork, called CAPONE. Based on UAV contextual information, the controller can predict UAV information without control message transmission. In addition, CAPONE divides the FANET into groups by computing the number of clusters using the Gap statistics method, which is input for a Fuzzy C-means method to determine the group leader and members. In this way, CAPONE reduces the bandwidth consumption and signaling overhead, while guaranteeing the control message delivering in FANET scenarios. Extensive simulations are used to show the gains of the CAPONE in terms of Packet Delivery Ratio, overhead, and energy compared to existing SDN-FANET architectures.

Formation of large oligomers of DOPAL-modified α-synuclein is modulated by the oxidation of methionine residues located at C-terminal domain.

The formation of neurotoxic oligomers of the presynaptic protein α-Synuclein (aSyn) is suggested to be associated with Parkinson's disease neurodegeneration. In this respect, it was demonstrated that the aldehyde 3,4-dihydroxyphenylacetaldehyde (DOPAL), a product from the enzymatic oxidation of dopamine, is capable of stabilizing potentially toxic aSyn oligomers via formation of covalent adducts with Lys residues of the protein. In addition, DOPAL-induced production of reactive oxygen species (ROS) leads to the oxidation of aSyn's Met residues to Met-sulfoxide. Recently, our group pointed out that the pre-oxidation of all-four Met residues of aSyn, upon treatment with H2O2, decreases the formation of large aSyn-DOPAL oligomers, which are suggested to be more toxic to neurons than the corresponding small oligomers (Carmo-Gonçalves et al., Biochem. Biophys. Res. Comm. 505, 295-301. 2018). By using a series of Met to Val mutants of aSyn, we demonstrated that the ability of aSyn to scavenge ROS/H2O2 generated from DOPAL oxidation is primarily dependent on Met residues located at the C-terminal domain of the protein, which contrasts with the reactivity of aSyn against H2O2 itself in which N-terminal Met residues (notably Met5) were more readily oxidized. Interestingly, the substitution of C-terminal Met residues (particularly Met127) by Val increased the formation of DOPAL-induced large oligomers in comparison with the wild-type protein. In this context, we demonstrated that the hydrophobicity of aSyn monomer, which is affected distinctively by the oxidation of N- versus C-terminal methionines, is correlated with the formation of large (but not small) oligomers of aSyn mediated by DOPAL.

Cooperative UAV Scheme for Enhancing Video Transmission and Global Network Energy Efficiency.

Collaboration between multiple Unmanned Aerial Vehicles (UAVs) to set up a Flying Ad Hoc Network (FANET) is a growing trend since future applications claim for more autonomous and rapid deployable systems. The user experience on watching videos transmitted over FANETs should always be satisfactory even under influence of topology changes caused by the energy consumption of UAVs. In addition, the FANET must keep the UAVs cooperating as much as possible during a mission. However, one of the main challenges in FANET is how to mitigate the impact of limited energy resources of UAVs on the FANET operation in order to monitor the environment for a long period of time. In this sense, UAV replacement is required in order to avoid the premature death of nodes, network disconnections, route failures, void areas, and low-quality video transmissions. In addition, decision-making must take into account energy consumption associated with UAV movements, since they are generally quite energy-intensive. This article proposes a cooperative UAV scheme for enhancing video transmission and global energy efficiency called VOEI. The main goal of VOEI is to maintain the video with QoE support while supporting the nodes with a good connectivity quality level and flying for a long period of time. Based on an Software Defined Network (SDN) paradigm, the VOEI assumes the existence of a centrailized controller node to compute reliable and energy-efficiency routes, as well as detects the appropriate moment for UAV replacement by considering global FANET context information to provide energy-efficiency operations. Based on simulation results, we conclude that VOEI can effectively mitigate the energy challenges of FANET, since it provides energy-efficiency operations, avoiding network death, route failure, and void area, as well as network partitioning compared to state-of-the-art algorithm. In addition, VOEI delivers videos with suitable Quality of Experience (QoE) to end-users at any time, which is not achieved by the state-of-the-art algorithm.

In vitro neurotoxicity of salsolinol is attenuated by the presynaptic protein α-synuclein.

BACKGROUND: Salsolinol (SALSO), a product from the reaction of dopamine (DA) with acetaldehyde, is found increased in dopaminergic neurons of Parkinson's disease (PD) patients. The administration of SALSO in rats causes myenteric neurodegeneration followed by the formation of deposits of the protein α-synuclein (aS), whose aggregation is intimately associated to PD. METHODS: NMR, isothermal titration calorimetry and MS were used to evaluate the interaction of SALSO with aS. The toxicity of SALSO and in vitro-produced aS-SALSO species was evaluated on mesencephalic primary neurons from mice. RESULTS: SALSO, under oxidative conditions, stabilizes the monomeric state besides a minor population of oligomers of aS, resulting in a strong inhibition of the fibrillation process. SALSO does not promote any chemical modification of the protein. Instead, the interaction of SALSO with aS seems to occur via hydrophobic effect, likely mediated by the NAC (non-amyloid component) domain of the protein. aS-SALSO species were found to be innocuous on primary neurons, while SALSO alone induces apoptosis via caspase-3 activation. Importantly, exogenous aS monomer was capable of protecting neurons against SALSO toxicity irrespective whether the protein was co-administered with SALSO or added until 2 h after SALSO, as evidenced by DAPI and cleaved-caspase 3 assays. Similar protective action of aS was found by pre-incubating neurons with aS before the administration of SALSO. CONCLUSIONS: Interaction of SALSO with aS leads to the formation of fibril-incompetent and innocuous adducts. SALSO toxicity is attenuated by aS monomer. SIGNIFICANCE: aS could exhibit a protective role against the neurotoxic effects of SALSO in dopaminergic neuron.

Suture and venous traction test analysis in dogs fixed in alcohol and preserved in saline solution / Análise de sutura e de teste de tração venosa em cães fixados em álcool e conservados em solução salina

The objective of this research was to determine in necropsied dogs the best time for fixation in ethylic alcohol (EA) and preservation in 30% sodium chloride aqueous solution (SCAS 30%), aiming micro-surgical training. Five groups of necropsied dogs (G1 to G5) were fixed with EA, and put in boxes containing EA for 30 (G2), 60 (G3), 90 (G4) or 120 days (G5). After that, each group was preserved in SCAS 30% for 120 days. The control group (G1) was composed by cadavers without fixation/preservation. At the end of each period, two fragments of external jugular vein per cadaver were collected, for traction test. Immediately after the collection, the cadavers femoral veins were evaluated (by 2 people) regarding the suture quality in binocular surgical microscope, and attributed scores from 0 (bad) to 5 (excellent), regarding the fresh samples. The average at the maximum rupture strength of the G3 fixation end (21.51N), such as the average of the G2 preserving end (21.62N) remained closer to the control group (19.98N) and the G2 was the group with the best score for venous suture training. The EA was efficient as a fixative just like SCAS as a dog cadavers' preservative. The small change of the traction test values, together with the best suture score, indicated the group kept for 30 days in EA and SCAS (G2) as the best for venous micro-surgical training.(AU)

O objetivo deste trabalho foi determinar, em cadáveres de cães, o melhor tempo para fixação em álcool etílico (AE) e conservação em solução aquosa de cloreto de sódio (SACS) a 30% visando o treinamento microcirúrgico. Cadáveres de cinco grupos (G1 a G5) foram fixados com AE e colocados em caixas contendo AE por 30 (G2), 60 (G3), 90 (G4) ou 120 days (G5). Depois, cada grupo foi conservado em SACS 30% por 120 dias. O grupo controle (G1) foi composto de cães sem fixação/conservação. Ao final de cada período, 2 fragmentos da veia jugular externa por cadáver foram coletados para o teste de tração. Imediatamente após a coleta, as veias femorais foram avaliadas (por 2 pessoas) em relação à qualidade da sutura em microscópio cirúrgico binocular, e atribuídos escores de 0 (péssimo) à 5 (excelente), em relação às amostras frescas. A média da força máxima de ruptura no G3 no final da fixação (21,51N), assim como a média do G2 no final da conservação (21,62N) foram as que mais se mantiveram próxima do grupo controle (19,98N) e o G2 foi o grupo com o melhor escore para treinamento da sutura venosa. O AE foi eficiente como fixador assim como a SACS foi efetiva na conservação de cadáveres de cães. A pequena alteração nos valores do teste de tração, junto com o melhor escore para sutura, indicaram o grupo mantido por 30 dias em AE e SACS (G2) como o melhor para treinamento venoso microcirúrgico.(AU)

A Medical Approach to the Monoamine Oxidase Inhibition by Using 7Hbenzo[ e]perimidin-7-one Derivatives.

BACKGROUND: A series of perimidinone derivatives (7H-benzo[e]perimidin-7-one) were synthesized and assessed by means of in vitro assays as human MAO inhibitors. These compounds inhibited reversibly the enzymes with inhibitory constants in the range of 2 to 20 µM. In addition, the selectivity of inhibition of the MAO isoforms seems to be significantly dependent of the presence either of heteroatom or electron donating and withdrawing groups on the perimidinone framework, which was verified by using molecular docking simulation with the crystallized MAO receptors. Most of these inhibitors were highly selective: 9 and 11 inhibited selectively the MAO-B isoform while 12 had 10-fold selectivity for MAO-A isoform. Moreover, the compound 12 was both the most selective and potent MAO-A inhibitor among perimidinones. RESULT: These results have important implications for the drug design of molecules targeting depression and movement-related disorders.

Oligomerization and Membrane-binding Properties of Covalent Adducts Formed by the Interaction of α-Synuclein with the Toxic Dopamine Metabolite 3,4-Dihydroxyphenylacetaldehyde (DOPAL).

Oxidative deamination of dopamine produces the highly toxic aldehyde 3,4-dihydroxyphenylacetaldehyde (DOPAL), enhanced production of which is found in post-mortem brains of Parkinson disease patients. When injected into the substantia nigra of rat brains, DOPAL causes the loss of dopaminergic neurons accompanied by the accumulation of potentially toxic oligomers of the presynaptic protein α-synuclein (aS), potentially explaining the synergistic toxicity described for dopamine metabolism and aS aggregation. In this work, we demonstrate that DOPAL interacts with aS via formation of Schiff-base and Michael-addition adducts with Lys residues, in addition to causing oxidation of Met residues to Met-sulfoxide. DOPAL modification leads to the formation of small aS oligomers that may be cross-linked by DOPAL. Both monomeric and oligomeric DOPAL adducts potently inhibit the formation of mature amyloid fibrils by unmodified aS. The binding of aS to either lipid vesicles or detergent micelles, which results in a gain of α-helix structure in its N-terminal lipid-binding domain, protects the protein against DOPAL adduct formation and, consequently, inhibits DOPAL-induced aS oligomerization. Functionally, aS-DOPAL monomer exhibits a reduced affinity for small unilamellar vesicles with lipid composition similar to synaptic vesicles, in addition to diminished membrane-induced α-helical content in comparison with the unmodified protein. These results suggest that DOPAL could compromise the functionality of aS, even in the absence of protein oligomerization, by affecting the interaction of aS with lipid membranes and hence its role in the regulation of synaptic vesicle traffic in neurons.

Pitfalls associated with the use of Thioflavin-T to monitor anti-fibrillogenic activity.

Thioflavin-T (ThT) is a cationic benzothiazole dye that displays enhanced fluorescence upon binding to amyloid fibrils. This property makes ThT the current reagent of choice for the quantification of amyloid fibrils. Herein, we investigate the main pitfalls associated with the use of ThT-based assays to monitor the fibrillation of α-synuclein (α-syn), a protein linked to Parkinson's disease and other α-synucleinopathies. We demonstrated for the first time that ThT interacts with α-syn disordered monomer and accelerates the protein fibrillation in vitro. As a consequence, misleading conclusions may arise from the use of ThT-based real-time assays in the evaluation of anti-fibrillogenic compounds. Interestingly, NMR experiments indicated that C-terminal domain of α-syn is the main region perturbed by ThT interaction, similarly to that found for the pesticide paraquat, a well-documented accelerator of α-syn fibrillation. Moreover, we demonstrated that certain potent inhibitors of α-syn fibrillation, such as oxidized catecholamines and polyphenols, undergo spontaneous oxidation in aqueous solution, generating compounds that strongly quench ThT fluorescence. In light of these findings, we alert for possible artifacts associated to the measure of the anti-fibrillogenic activity based only on ThT fluorescence approach.

Beyond topoisomerase inhibition: antitumor 1,4-naphthoquinones as potential inhibitors of human monoamine oxidase.

Monoamine oxidase (MAO) action has been involved in the regulation of neurotransmitters levels, cell signaling, cellular growth, and differentiation as well as in the balance of the intracellular polyamine levels. Although so far obscure, MAO inhibitors are believed to have some effect on tumors progression. 1,4-naphthoquinone (1,4-NQ) has been pointed out as a potential pharmacophore for inhibition of both MAO and DNA topoisomerase activities, this latter associated with antitumor activity. Herein, we demonstrated that certain antitumor 1,4-NQs, including spermidine-1,4-NQ, lapachol, and nor-lapachol display inhibitory activity on human MAO-A and MAO-B. Kinetic studies indicated that these compounds are reversible and competitive MAO inhibitors, being the enzyme selectivity greatly affected by substitutions on 1,4-NQ ring. Molecular docking studies suggested that the most potent MAO inhibitors are capable to bind to the MAO active site in close proximity of flavin moiety. Furthermore, ability to inhibit both MAO-A and MAO-B can be potentialized by the formation of hydrogen bonds between these compounds and FAD and/or the residues in the active site. Although spermidine-1,4-NQs exhibit antitumor action primarily by inhibiting topoisomerase via DNA intercalation, our findings suggest that their effect on MAO activity should be taken into account when their application in cancer therapy is considered.

α-Synuclein as an intrinsically disordered monomer--fact or artefact?

Fibrillization of the protein α-synuclein (α-syn) is a hallmark of Parkinson's disease and other α-synucleinopathies. The well-established idea that α-syn is a natively disordered monomer prone to forming fibrils was recently challenged by data showing that the protein mostly exists in vitro and in vivo as helically folded tetramers that are resistant to fibrillization. These apparently conflicting findings may be reconciled by the idea that α-syn exists as a disordered monomer in equilibrium with variable amounts of dynamic oligomeric species. In this context, varying the approaches used for protein purification, such as the method used to lyse cells or the inclusion of denaturing agents, could dramatically perturb this equilibrium and hence alter the relative abundance of the disordered monomer. In the present study, we investigated how the current methods for α-syn purification affect the structure and oligomeric state of the protein, and we discuss the main pitfalls associated with the production of recombinant α-syn in Escherichia coli. We demonstrate that α-syn was expressed in E. coli as a disordered monomer independent of both the cell lysis method and the use of heating/acidification for protein purification. In addition, we provide convincing evidence that the disordered monomer exists in equilibrium with a dynamic dimer, which is not an artefact of the cross-linking protocol as previously suggested. Unlike the helically folded tetramer, α-syn dimer is prone to fibrillate and thus it may be an interesting target for anti-fibrillogenic molecules.

A routing protocol based on energy and link quality for Internet of Things applications.

The Internet of Things (IoT) is attracting considerable attention from the universities, industries, citizens and governments for applications, such as healthcare, environmental monitoring and smart buildings. IoT enables network connectivity between smart devices at all times, everywhere, and about everything. In this context, Wireless Sensor Networks (WSNs) play an important role in increasing the ubiquity of networks with smart devices that are low-cost and easy to deploy. However, sensor nodes are restricted in terms of energy, processing and memory. Additionally, low-power radios are very sensitive to noise, interference and multipath distortions. In this context, this article proposes a routing protocol based on Routing by Energy and Link quality (REL) for IoT applications. To increase reliability and energy-efficiency, REL selects routes on the basis of a proposed end-to-end link quality estimator mechanism, residual energy and hop count. Furthermore, REL proposes an event-driven mechanism to provide load balancing and avoid the premature energy depletion of nodes/networks. Performance evaluations were carried out using simulation and testbed experiments to show the impact and benefits of REL in small and large-scale networks. The results show that REL increases the network lifetime and services availability, as well as the quality of service of IoT applications. It also provides an even distribution of scarce network resources and reduces the packet loss rate, compared with the performance of well-known protocols.

Vitamins K interact with N-terminus α-synuclein and modulate the protein fibrillization in vitro. Exploring the interaction between quinones and α-synuclein.

In the last decades, a series of compounds, including quinones and polyphenols, has been described as having anti-fibrillogenic action on α-synuclein (α-syn) whose aggregation is associated to the pathogenesis of Parkinson's disease (PD). Most of these molecules act as promiscuous anti-amyloidogenic agents, interacting with the diverse amyloidogenic proteins (mostly unfolded) through non-specific hydrophobic interactions. Herein we investigated the effect of the vitamins K (phylloquinone, menaquinone and menadione), which are 1,4-naphthoquinone (1,4-NQ) derivatives, on α-syn aggregation, comparing them with other anti-fibrillogenic molecules such as quinones, polyphenols and lipophilic vitamins. Vitamins K delayed α-syn fibrillization in substoichiometric concentrations, leading to the formation of short, sheared fibrils and amorphous aggregates, which are less prone to produce leakage of synthetic vesicles. In seeding conditions, menadione and 1,4-NQ significantly inhibited fibrils elongation, which could be explained by their ability to destabilize preformed fibrils of α-syn. Bidimensional NMR experiments indicate that a specific site at the N-terminal α-syn (Gly31/Lys32) is involved in the interaction with vitamins K, which is corroborated by previous studies suggesting that Lys is a key residue in the interaction with quinones. Together, our data suggest that 1,4-NQ, recently showed up by our group as a potential scaffold for designing new monoamine oxidase inhibitors, is also capable to modulate α-syn fibrillization in vitro.

Molecular insights into human monoamine oxidase (MAO) inhibition by 1,4-naphthoquinone: evidences for menadione (vitamin K3) acting as a competitive and reversible inhibitor of MAO.

Monoamine oxidase (MAO) catalyzes the oxidative deamination of biogenic and exogenous amines and its inhibitors have therapeutic value for several conditions including affective disorders, stroke, neurodegenerative diseases and aging. The discovery of 2,3,6-trimethyl-1,4-naphthoquinone (TMN) as a nonselective and reversible inhibitor of MAO, has suggested 1,4-naphthoquinone (1,4-NQ) as a potential scaffold for designing new MAO inhibitors. Combining molecular modeling tools and biochemical assays we evaluate the kinetic and molecular details of the inhibition of human MAO by 1,4-NQ, comparing it with TMN and menadione. Menadione (2-methyl-1,4-naphthoquinone) is a multitarget drug that acts as a precursor of vitamin K and an inducer of mitochondrial permeability transition. Herein we show that MAO-B was inhibited competitively by 1,4-NQ (K(i)=1.4 µM) whereas MAO-A was inhibited by non-competitive mechanism (K(i)=7.7 µM). Contrasting with TMN and 1,4-NQ, menadione exhibited a 60-fold selectivity for MAO-B (K(i)=0.4 µM) in comparison with MAO-A (K(i)=26 µM), which makes it as selective as rasagiline. Fluorescence and molecular modeling data indicated that these inhibitors interact with the flavin moiety at the active site of the enzyme. Additionally, docking studies suggest the phenyl side groups of Tyr407 and Tyr444 (for MAO-A) or Tyr398 and Tyr435 (for MAO-B) play an important role in the interaction of the enzyme with 1,4-NQ scaffold through forces of dispersion as verified for menadione, TMN and 1,4-NQ. Taken together, our findings reveal the molecular details of MAO inhibition by 1,4-NQ scaffold and show for the first time that menadione acts as a competitive and reversible inhibitor of human MAO.