Selective impact of Tau loss on nociceptive primary afferents and pain sensation

Tau protein hyperphosphorylation and consequent malfunction are hallmarks of Alzheimer's disease pathology; importantly, pain perception is diminished in these patients. In physiological conditions, Tau contributes to cytoskeletal dynamics and in this way, influences a number of cellular mechanisms including axonal trafficking, myelination and synaptic plasticity, processes that are also implicated in pain perception. However, there is no in vivo evidence clarifying the role of Tau in nociception. Thus, we tested Tau-null (Tau-/-) and Tau+/+ mice for acute thermal pain (Hargreaves' test), acute and tonic inflammatory pain (formalin test) and mechanical allodynia (Von Frey test). We report that Tau-/- animals presented a decreased response to acute noxious stimuli when compared to Tau+/+ while their pain-related behavior is augmented under tonic painful stimuli. This increased reactivity to tonic pain was accompanied by enhanced formalin-evoked c-fos staining of second order nociceptive neurons at Tau-null dorsal horn. In addition, we analyzed the primary afferents conveying nociceptive signals, estimating sciatic nerve fiber density, myelination and nerve conduction. Ultrastructural analysis revealed a decreased C-fiber density in the sciatic nerve of Tau-null mice and a hypomyelination of myelinated fibers (Ad-fibers) - also confirmed by western blot analysis - followed by altered conduction properties of Tau-null sciatic nerves. To our knowledge, this is the first in vivo study that demonstrates that Tau depletion negatively affects the main systems conveying nociceptive information to the CNS, adding to our knowledge about Tau function(s) that might also be relevant for understanding peripheral neurological deficits in different Tauopathies.We would like to thank Drs Joao Relvas, Joana Paes de Faria Monteiro and Nuno Dias for their comments in this work. Many thanks to Dr Joao Relvas for the MBP antibody. The work was supported by grants "SFRH/BPD/80118/2011", "PTDC/SAU-NMC/113934/2009" funded by FCT - Portuguese Foundation for Science and Technology and project DoIT - Desenvolvimento e Operacionalizacao da Investigacao de Translacao (No. do projeto 13853), funded by Fund Europeu de Desenvolvimento Regional (FEDER) through the Programa Operacional Fatores de Competitividade (POFC). Author's contributions: experimental design - IS, HA, VP, AA, and NS; performed research - IS, HA, VP, AL, SL, SS, SP, AC, FPR, and RF; data analyses - IS, HA, AL, VP, SC, and FPR; and manuscript preparation - IS, HA, VP, and NS

Phase Competitions behind the Giant Magnetic Entropy Variation: Gd5Si2Ge2 and Tb5Si2Ge2 Case Studies

Magnetic materials with strong spin-lattice coupling are a powerful set of candidates for multifunctional applications because of their multiferroic, magnetocaloric (MCE), magnetostrictive and magnetoresistive effects. In these materials there is a strong competition between two states (where a state comprises an atomic and an associated magnetic structure) that leads to the occurrence of phase transitions under subtle variations of external parameters, such as temperature, magnetic field and hydrostatic pressure. In this review a general method combining detailed magnetic measurements/analysis and first principles calculations with the purpose of estimating the phase transition temperature is presented with the help of two examples (Gd5Si2Ge2 and Tb5Si2Ge2). It is demonstrated that such method is an important tool for a deeper understanding of the (de)coupled nature of each phase transition in the materials belonging to the R5(Si,Ge)4 family and most possibly can be applied to other systems. The exotic Griffiths-like phase in the framework of the R5(SixGe1-x)4 compounds is reviewed and its generalization as a requisite for strong phase competitions systems that present large magneto-responsive properties is proposed

LaMMos - Latching Mechanism based on Motorized-screw for Reconfigurable Robots and Exoskeleton Suits

Reconfigurable robots refer to a category of robots that their components (individual joints and links) can be assembled in multiple configurations and geometries. Most of existing latching mechanisms are based on physical tools such as hooks, cages or magnets, which limit the payload capacity. Therefore, robots re- quire a latching mechanism which can help to reconfigure itself without sacrificing the payload capability. This paper presents a latching mechanism based on the flexible screw attaching principle. In which, actuators are used to move the robot links and joints while connecting them with a motorized-screw and dis- connecting them by unfastening the screw. The brackets used in our mechanism configuration helps to hold maximum force up to 5000N. The LaMMos - Latching Mechanism based on Motorized- screw has been applied to the DeWaLoP - Developing Water Loss Prevention in-pipe robot. It helps the robot to shrink its body to crawl into the pipe with minimum diameter, by recon- figuring the leg positions. And it helps to recover the legs positions to original status once the robot is inside the pipe. Also, LaMMos add stiffness to the robot legs by dynamically integrate them to the structure. Additionally, we present an application of the LaMMos mechanism to exoskeleton suits, for easing the mo- tors from the joints when carrying heavy weights for long periods of time. This mechanism offers many interesting opportunities for robotics research in terms of functionality, pay- load and size.Comment: 14 pages, 15 figure

Open-source tool for real-time and automated analysis of droplet-based microfluidic

Publisher Copyright: © 2023 The Royal Society of Chemistry.Droplet-based microfluidic technology is a powerful tool for generating large numbers of monodispersed nanoliter-sized droplets for ultra-high throughput screening of molecules or single cells. Yet further progress in the development of methods for the real-time detection and measurement of passing droplets is needed for achieving fully automated systems and ultimately scalability. Existing droplet monitoring technologies are either difficult to implement by non-experts or require complex experimentation setups. Moreover, commercially available monitoring equipment is expensive and therefore limited to a few laboratories worldwide. In this work, we validated for the first time an easy-to-use, open-source Bonsai visual programming language to accurately measure in real-time droplets generated in a microfluidic device. With this method, droplets are found and characterized from bright-field images with high processing speed. We used off-the-shelf components to achieve an optical system that allows sensitive image-based, label-free, and cost-effective monitoring. As a test of its use we present the results, in terms of droplet radius, circulation speed and production frequency, of our method and compared its performance with that of the widely-used ImageJ software. Moreover, we show that similar results are obtained regardless of the degree of expertise. Finally, our goal is to provide a robust, simple to integrate, and user-friendly tool for monitoring droplets, capable of helping researchers to get started in the laboratory immediately, even without programming experience, enabling analysis and reporting of droplet data in real-time and closed-loop experiments.publishersversionepub_ahead_of_prin

Complete mitochondrial genomes of the freshwater mussels Amblema plicata (Say, 1817), Pleurobema oviforme (Conrad, 1834), and Popenaias popeii (Lea, 1857) (Bivalvia: Unionidae: Ambleminae)

Freshwater mussels are a critically imperiled group of mollusks that play key ecological roles and provide important services to humans. The Ambleminae is the only subfamily of these mussels, endemic to North America. Complete mitogenomes have only been sequenced for two of five tribes of the subfamily. Pleurobema oviforme, Amblema plicata, and Popenaias popeii each belong to tribes Pleurobemini, Amblemini, and Popenaidini, respectively, and have not had published mitogenomes. Thus, this study aims to present the complete mitogenomes for these species, to provide a phylogeny of the Ambleminae and confirm the gene arrangements with representation from each of its tribes. The newly sequenced mitogenomes range from 15,852 to 15,993 nucleotides, are composed of 13 PCGs, 22 tRNAs, and two rRNAs and all share the same (UF1) gene order.This work was supported by Portuguese Foundation for Science and Technology (FCT) [grant number ConBioMics/BI-Lic/2019-037 (JTT), grant number SFRH/BD/137935/2018 (AGS)]; COMPETE 2020, Portugal 2020 and the European Union through the ERDF, and by Portuguese Foundation for Science and Technology (FCT) through national funds [UID/Multi/04423/2019] under project ConBiomics: the missing approach for the Conservation of Bivalves Project, and [project number NORTE-01- 0145-FEDER-030286]. Fieldwork in Texas was funded by the U.S. Fish and Wildlife Service, and Texas Parks and Wildlife Department (TPWD) as a Joint Traditional Section 6 Project 407348.info:eu-repo/semantics/publishedVersio

A simple architecture with self-assembled monolayers to build immunosensors for detecting the pancreatic cancer biomarker CA19-9

Accepted ManuscriptThe challenge of the early diagnosis of pancreatic cancer in routine clinical practice requires low-cost means of detection, and this may be achieved with immunosensors based on electrical or electrochemical principles. In this paper, we report a potentially low-cost immunosensor built with interdigitated gold electrodes coated with a self-assembled monolayer and a layer of anti-CA19-9 antibodies, which is capable of detecting the pancreatic cancer biomarker CA19-9 using electrical impedance spectroscopy. Due to specific, irreversible adsorption of CA19-9 onto its corresponding antibody, according to data from polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS), the immunosensor is highly sensitive and selective. It could detect CA19-9 in commercial samples with a limit of detection of 0.68 U mL−1, in addition to distinguishing between blood serum samples from patients with different concentrations of CA19-9. Furthermore, by treating the capacitance data with information visualization methods, we were able to verify the selectivity and robustness of the immunosensor with regard to false positives, as the samples containing higher CA19-9 concentrations, including those from tumor cells, could be distinguished from those with possible interferents.CAPES, FAPESP (Grant 2013/14262-7 and 2012/15543-7), CNPq (150985/2017-7), nBioNet network and Barretos Cancer Hospital for financial supportinfo:eu-repo/semantics/publishedVersio