Venomous animals from distinct phyla such as spiders, scorpions, snakes, cone snails, or sea anemones produce small toxic proteins interacting with a variety of cell targets. Their bites often cause pain. One of the ways of pain generation is the activation of TRPV1 channels. Screening of 30 different venoms from spiders and sea anemones for modulation of TRPV1 activity revealed inhibitors in tropical sea anemone Heteractis crispa venom. Several separation steps resulted in isolation of an inhibiting compound. This is a 56-residue-long polypeptide named APHC1 that has a Bos taurus trypsin inhibitor (BPTI)/Kunitztype fold, mostly represented by serine protease inhibitors and ion channel blockers. APHC1 acted as a partial antagonist of capsaicin-induced currents (32 ؎ 9% inhibition) with half-maximal effective concentration (EC 50 ) 54 ؎ 4 nM. In vivo, a 0.1 mg/kg dose of APHC1 significantly prolonged tail-flick latency and reduced capsaicin-induced acute pain. Therefore, our results can make an important contribution to the research into molecular mechanisms of TRPV1 modulation and help to solve the problem of overactivity of this receptor during a number of pathological processes in the organism.During the evolutionary process, different poisonous animals combined a set of bioactive compounds in their venoms used mainly to paralyze prey and/or as a defense against predators (1, 2). Bites of these creatures may induce inflammation, pain, tissue necrosis, allergic reactions, and neurotoxic effects such as convulsions, paralysis, respiratory failure, and cardiovascular stroke (3). Numerous toxic peptides are found within these venoms, and some of them can discriminate between closely related cellular targets that make them attractive for drug development and scientific use (4). Molecules accounting for lethal and inflammation effects of venoms have been extensively characterized, but less is known about the properties of other compounds. We concentrated on searching the compounds able to reduce TRPV1 2 conductivity. These receptors are expressed in mammalians in small and medium size dorsal root ganglion neurons and are localized in peripheral and central neuronal system (5-7). At present, it is accepted that TRPV1 receptors are molecular integrators of pain stimulus and initiate neuronal response during inflammation. Experiments with knock-out mice lacking the gene of vanilloid receptor clearly demonstrate its role in pain perception (8, 9). Since vanilloid receptor had been disclosed and cloned in 1997, it became an object of numerous investigations as a potential target for novel drugs against pain of different origin (10). As recently reported, vanillotoxins from a tarantula Psalmopoeus cambridgei directly activate TRPV1 in micromolar concentrations, causing pain effect in the same way as capsaicin does (11). Venoms of several jellyfish also seem to interact with TRPV1, knocking down its desensitization (12). A number of small molecules were synthesized that selectively inhibit TRPV1 in nanomolar concentration ...

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Ambient gas detection and measurement had become essential in diverse fields and applications, from preventing accidents, avoiding equipment malfunction, to air pollution warnings and granting the correct gas mixture to patients in hospitals. Gas leakage can reach large proportions, affecting entire neighborhoods or even cities, causing enormous environmental impacts. This paper elaborates on a deep review of the state of the art on gas-sensing technologies, analyzing the opportunities and main characteristics of the transducers, as well as towards their integration through the Internet of Things (IoT) paradigm. This should ease the information collecting and sharing processes, granting better experiences to users, and avoiding major losses and expenses. The most promising wireless-based solutions for ambient gas monitoring are analyzed and discussed, open research topics are identified, and lessons learned are shared to conclude the study.Technologies to sense gases and wireless communications support are elaborated in Sections 5 and 6, respectively. The most promising solutions in terms of sensing methods and IoT-enabled solutions are discussed in Section 7 and open research topics are identified. Lessons learned are shared at Section 8 and, finally, Section 9 concludes the study. Background on Environmental GasesSome gases are the key to ensure the functionality of systems and entire industries, as well as the presence of other gases being a problem in other fields, causing the loss of entire production lines, as in the food industry, or even cause the loss of lives and explosions. In this section, the most important gases in terms of pollution monitoring and control, health issues, and accident prevention are listed with their main characteristics.Oxygen (O 2 ) is the most important gas for life, and is crucial in numerous fields. Patients under anesthesia, or recovering from surgery and from certain diseases need controlled O 2 doses to keep them alive and fully recovered. The decrease of oxygen levels in enclosed spaces can be related with other gases leakage, which would lead people inside these spaces to asphyxiate, leading to an unconscious state, or even to death [29]. Numerous industrial processes rely on the correct concentration of this gas to achieve the best results, mainly chemical and combustion, which without the correct percentages will not grant the best performance of systems. Engine control systems depend on the correct mixture to achieve the expected performances, whether it is lower fuel consumption or power and speed [29][30][31][32].Carbon dioxide (CO 2 ) is a colorless, odorless gas, generated by the oxidation and combustion of hydrocarbon, as well as by living beings in the respiration process. It is a key gas for the greenhouse effect, and the increase of its levels, in the presence of other gases, is related with atmospheric pollution. It is also the key gas on the oxygen production by the photosynthesis process. The accumulation of this gas in enclosed spaces can be responsible to s...

Lynx1 is a GPI-tethered protein colocalized with nicotinic acetylcholine receptors (nAChRs) in the brain areas important for learning and memory. Previously, we demonstrated that at low micromolar concentrations the water-soluble Lynx1 variant lacking GPI-anchor (ws-Lynx1) acts on α7-nAChRs as a positive allosteric modulator. We hypothesized that ws-Lynx1 could be used for improvement of cognitive processes dependent on nAChRs. Here we showed that 2 µM ws-Lynx1 increased the acetylcholine-evoked current at α7-nAChRs in the rat primary visual cortex L1 interneurons. At higher concentrations ws-Lynx1 inhibits α7-nAChRs expressed in Xenopus laevis oocytes with IC 50 ~ 50 µM. In mice, ws-Lynx1 penetrated the bloodbrain barrier upon intranasal administration and accumulated in the cortex, hippocampus, and cerebellum. Chronic ws-Lynx1 treatment prevented the olfactory memory and motor learning impairment induced by the α7-nAChRs inhibitor methyllycaconitine (MLA). Enhanced long-term potentiation and increased paired-pulse facilitation ratio were observed in the hippocampal slices incubated with ws-Lynx1 and in the slices from ws-Lynx1-treated mice. Long-term potentiation blockade observed in MLA-treated mice was abolished by ws-Lynx1 co-administration. To understand the mechanism of ws-Lynx1 action, we studied the interaction of ws-Lynx1 and MLA at α7-nAChRs, measured the basal concentrations of endogenous Lynx1 and the α7 nAChR subunit and their association in the mouse brain. Our findings suggest that endogenous Lynx1 limits α7-nAChRs activation in the adult brain. Ws-Lynx1 partially displaces Lynx1 causing positive modulation of α7-nAChRs and enhancement 42) for the binding to the nAChR subunits, abolishes the Aβ 1-42 cytotoxic effect in the cultured cortical neurons (Thomsen et al., 2016), and prevents the long-term potentiation (LTP) blockade caused by Aβ 1-42 (Bychkov et al., 2018). Here, we investigated the ws-Lynx1 influence on cognitive processes in vivo and on the synaptic plasticity processes ex vivo. To model cognitive impairment associated with the loss of nAChR function, C57BL/6 mice were chronically treated with of synaptic plasticity. Ws-Lynx1 and similar compounds may constitute useful hits for treatment of cognitive deficits associated with the cholinergic system dysfunction.

The significant increase in energy consumption by the growth of the population or by the use of new equipment has brought big challenges to the energy security as well as the environment. There is a need that consumers can track their daily use and understand consumption standards for better organizing themselves to obtain financial and energetic efficiency. With the improvement of smart networks technology for better energy supply, a smart meter is not just a simple measurement gadget anymore, but it has additional functions including smart equipment control, bidirectional communication that allows integration of users and networks, and other functionalities. Smart meters are the most fundamental components in smart power grids. Besides, the meters used with a management system can be utilized for monitoring and controlling home appliances and other gadgets according to the users' need. A solution of an integrated and single system should be more efficient and economical. Smart measurement systems allow monitoring the energy consumption of the final consumers while providing useful information about the energy quality. The information provided by these systems is used by the operators to enhance the energy supply, and different techniques can be also applied for this end, such as charge scheduling, management from the demand side, and nonintrusive load monitoring. The Internet of Things (IoT) is becoming a great ally in the management of smart distribution and energy consumption in smart systems scenarios. To address these issues, this paper proposes and demonstrates a new smart energy meter following an IoT approach and its associated costs and benefits. The developed device incorporates several communication interfaces. In order to easily integrate with any monitoring software solution, the meter has a multi-protocol connection. Finally, the provided solution is validated and demonstrated in real-life environments and it is also under use.