Fabrication of low electrical percolation threshold multi-walled carbon nanotube sensors using magnetic patterning

Soft robotics is an expanding area with multiple applications; however, building low-cost, soft, and flexible robots requires the development of sensors that can be directly integrated into the soft robotics fabrication process. Thus, the motivation for this work was the design of a low-cost fabrication process of flexible sensors that can detect touch and deformation. The fabrication process proposed uses a flexible polymer nanocomposite with permanent magnets strategically placed where the conductive electrodes should be. The nanocomposite is based on poly(dimethylsiloxane) (PDMS) and multi-walled carbon nanotubes (MWCNTs). The MWCNT contains ferromagnetic impurities remaining from the synthesis process, which can be used for magnetic manipulation. Several electrode geometries were successfully simulated and tested. The magnetic patterning was simulated, allowing the fabrication of conductive patterns within the composite. This fabrication process allowed the reduction of the electrical resistivity of the nanocomposites as compared to the composites with homogeneous MWCNT dispersion. It also allowed the fabrication of piezoresistive and triboelectric sensors at MWCNT concentration as low as 0.5 wt.%. The fabrication process proposed is flexible, allows the development of sensors for soft robotics, as well as monitoring large and unconventional areas, and may be adapted to different mould shapes and polymers at low cost.This research is part of the PhD project at the Doctoral Program in Advanced Materials and Processing—FEUP. We would like to thank CeNTI for providing resources (labs, equipment and consumables) to perform the fabrication and characterisation of the samples. The authors thank CEMUP for expert assistance (Rui Rocha) with SEM-EDS. IPC acknowledges the support of FCT through National Funds References UIDB/05256/2020 and UIDP/05256/2020

Cox-2 inhibition with nutraceuticals: a new therapeutic approach against Helicobacter pylori infection

Abstract no.: P3.7 publicado em: Helicobacter 2012;17(Suppl.1):98Accumulated evidence in humans and animals shows that H. pylori up-regulate the expression of cyclooxygenase (COX)-2 both at mRNA and protein levels which might be one of the mechanisms leading to several gastric diseases. Aim: To study the expression of COX-2 on mice gastric mucosa during long-term treatment with two nutraceuticals: curcumin and synbiotic 2000 on H. pylori experimental chronic infection. Materials and Methods: We infected 45 C57BL/6 mice with SS1 – H. pylori strain. After infection confirmation by 13C-urea breath test mice where then treated with either PBS, curcumin (10 mg/mouse) or Synbiotic 2000 (50 mg/ mouse), three times per week. Five mice from each treatment group were euthanized at week 6, 18 and 27. Gastric samples were removed for COX-2 immunohistochemistry analysis. Results: All the 45 mice were Hp positive by 13C-urea breath test and immunohistochemistry. In the PBS group the production of COX-2 was significantly up-regulated at week 6 (area of positive immunostaining 393–544 · 103 pixels), 18 (area of positive immunostaining 242–614 · 103 pixels) and 27 week (area of positive immunostaining 129–175 · 103 pixels). The treatment with either curcumin or synbiotic significantly decreased the expression of COX-2 at all time points. Conclusions: These results suggest the therapeutic usefulness of both nutraceuticals on COX-2 inhibition during chronic experimental mice H. pylori infection. The supplementation of diet in humans with curcumin or Synbiotic 2000 may be a novel therapeutic approach against gastric inflammation induced by Hp infection

Deletion of iRhom2 protects against diet-inducedobesity by increasing thermogenesis

Objective:Obesity is the result of positive energy balance. It can be caused by excessive energy consumption but also by decreased energydissipation, which occurs under several conditions including when the development or activation of brown adipose tissue (BAT) is impaired. Herewe evaluated whether iRhom2, the essential cofactor for the Tumour Necrosis Factor (TNF) sheddase ADAM17/TACE, plays a role in thepathophysiology of metabolic syndrome.Methods:We challenged WT versus iRhom2 KO mice to positive energy balance by chronic exposure to a high fat diet and then compared theirmetabolic phenotypes. We also carried outex vivoassays with primary and immortalized mouse brown adipocytes to establish the autonomy ofthe effect of loss of iRhom2 on thermogenesis and respiration.Results:Deletion of iRhom2 protected mice from weight gain, dyslipidemia, adipose tissue inflammation, and hepatic steatosis and improvedinsulin sensitivity when challenged by a high fat diet. Crucially, the loss of iRhom2 promotes thermogenesis via BAT activation and beigeadipocyte recruitment, enabling iRhom2 KO mice to dissipate excess energy more efficiently than WT animals. This effect on enhanced ther-mogenesis is cell-autonomous in brown adipocytes as iRhom2 KOs exhibit elevated UCP1 levels and increased mitochondrial proton leak.Conclusion:Our data suggest that iRhom2 is a negative regulator of thermogenesis and plays a role in the control of adipose tissue homeostasisduring metabolic diseaseWellcome Trust strategic award (100574/Z/12/Z) and MRC MDU (MC_UU_12012/

Thousands of Rab GTPases for the Cell Biologist

Rab proteins are small GTPases that act as essential regulators of vesicular trafficking. 44 subfamilies are known in humans, performing specific sets of functions at distinct subcellular localisations and tissues. Rab function is conserved even amongst distant orthologs. Hence, the annotation of Rabs yields functional predictions about the cell biology of trafficking. So far, annotating Rabs has been a laborious manual task not feasible for current and future genomic output of deep sequencing technologies. We developed, validated and benchmarked the Rabifier, an automated bioinformatic pipeline for the identification and classification of Rabs, which achieves up to 90% classification accuracy. We cataloged roughly 8.000 Rabs from 247 genomes covering the entire eukaryotic tree. The full Rab database and a web tool implementing the pipeline are publicly available at www.RabDB.org. For the first time, we describe and analyse the evolution of Rabs in a dataset covering the whole eukaryotic phylogeny. We found a highly dynamic family undergoing frequent taxon-specific expansions and losses. We dated the origin of human subfamilies using phylogenetic profiling, which enlarged the Rab repertoire of the Last Eukaryotic Common Ancestor with Rab14, 32 and RabL4. Furthermore, a detailed analysis of the Choanoflagellate Monosiga brevicollis Rab family pinpointed the changes that accompanied the emergence of Metazoan multicellularity, mainly an important expansion and specialisation of the secretory pathway. Lastly, we experimentally establish tissue specificity in expression of mouse Rabs and show that neo-functionalisation best explains the emergence of new human Rab subfamilies. With the Rabifier and RabDB, we provide tools that easily allows non-bioinformaticians to integrate thousands of Rabs in their analyses. RabDB is designed to enable the cell biology community to keep pace with the increasing number of fully-sequenced genomes and change the scale at which we perform comparative analysis in cell biology

Cytokine responses of CD4⁺T cells during a <it>Plasmodium chabaudi chabaudi </it>(ER) blood-stage infection in mice initiated by the natural route of infection

Abstract Background Investigation of host responses to blood stages of Plasmodium spp, and the immunopathology associated with this phase of the life cycle are often performed on mice infected directly with infected red blood cells. Thus, the effects of mosquito bites and the pre-erythrocytic stages of the parasite, which would be present in natural infection, are ignored In this paper, Plasmodium chabaudi chabaudi infections of mice injected directly with infected red blood cells were compared with those of mice infected by the bites of infected mosquitoes, in order to determine whether the courses of primary infection and splenic CD4 T cell responses are similar. Methods C57Bl/6 mice were injected with red blood cells infected with P. chabaudi (ER) or infected via the bite of Anopheles stephensi mosquitoes. Parasitaemia were monitored by Giemsa-stained thin blood films. Total spleen cells, CD4+ T cells, and cytokine production (IFN-γ, IL-2, IL-4, IL-10) were analysed by flow cytometry. In some experiments, mice were subjected to bites of uninfected mosquitoes prior to infectious bites in order to determine whether mosquito bites per se could affect a subsequent P. chabaudi infection. Results P. chabaudi (ER) infections initiated by mosquito bite were characterized by lower parasitaemia of shorter duration than those observed after direct blood challenge. However, splenomegaly was comparable suggesting that parasitaemia alone does not account for the increase in spleen size. Total numbers of CD4 T cells and those producing IFN-γ, IL-10 and IL-2 were reduced in comparison to direct blood challenge. By contrast, the reduction in IL-4 producing cells was less marked suggesting that there is a proportionally lower Th1-like response in mice infected via infectious mosquitoes. Strikingly, pre-exposure to bites of uninfected mosquitoes reduced the magnitude and duration of the subsequent mosquito-transmitted infection still further, but enhanced the response of CD4 T cells producing IFN-γ and IL-4. Conclusion The data in this paper suggest that studying early host responses in blood stage malaria infections measured after direct blood challenge of mice may not completely reflect the natural situation, and more detailed investigations of blood-stage immunity after mosquito transmission in experimental models should be considered.</p

Rab GTPase regulation of bacteria and protozoa phagocytosis occurs through the modulation of phagocytic receptor surface expression

Abstract Phagocytosis of invading microorganisms by professional phagocytic cells has a central role in innate immunity. However, several microorganisms developed strategies to subvert this process. Previously, we reported that bacteria and protozoa modulate differently the expression of Rab GTPases. Moreover, our results suggested that this modulation can contribute to avoid phagocytosis. Here, we investigated the mechanism by which the malaria parasite Plasmodium berghei and the bacterium Escherichia coli subvert phagocytosis through the modulation of Rab14 or Rab9a expression, respectively. We first confirmed that the scavenger receptor CD36 and the Toll-like receptor (TLR) 4 are required for the phagocytosis of P. berghei and E. coli, respectively. Interestingly, we observed that Rab14 silencing leads to an increase in the surface expression of CD36 in macrophages, which can explain the increase in the phagocytosis of P. berghei we reported previously. Similar results were obtained for Rab9a and TLR4, i.e. Rab9a silencing causes an upregulation of TLR4 surface expression in macrophages. Furthermore, we found that the decrease in the internalization of CD36 and TLR4, upon Rab14 or Rab9a silencing, respectively, can explain the increase in the surface levels of these receptors. Thus, our studies provide evidence that the modulation of phagocytosis caused by changes in Rab expression is operated, at least partly through changes in the surface levels of phagocytic receptors