Integrated Design and Fabrication of Pneumatic Soft Robot Actuators in a Single Casting Step.

Bio-inspired soft robots have already shown the ability to handle uncertainty and adapt to unstructured environments. However, their availability is partially restricted by time-consuming, costly, and highly supervised design-fabrication processes, often based on resource-intensive iterative workflows. Here, we propose an integrated approach targeting the design and fabrication of pneumatic soft actuators in a single casting step. Molds and sacrificial water-soluble hollow cores are printed using fused filament fabrication. A heated water circuit accelerates the dissolution of the core's material and guarantees its complete removal from the actuator walls, while the actuator's mechanical operability is defined through finite element analysis. This enables the fabrication of actuators with non-uniform cross-sections under minimal supervision, thereby reducing the number of iterations necessary during the design and fabrication processes. Three actuators capable of bending and linear motion were designed, fabricated, integrated, and demonstrated as 3 different bio-inspired soft robots, an earthworm-inspired robot, a 4-legged robot, and a robotic gripper. We demonstrate the availability, versatility, and effectiveness of the proposed methods, contributing to accelerating the design and fabrication of soft robots. This study represents a step toward increasing the accessibility of soft robots to people at a lower cost.

Activity-dependent diffusion trapping of AMPA receptors as a key step for expression of early LTP.

This review focuses on the activity-dependent diffusion trapping of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as a crucial mechanism for the expression of early long-term potentiation (LTP), a process central to learning and memory. Despite decades of research, the precise mechanisms by which LTP induction leads to an increase in AMPAR responses at synapses have been elusive. We review the different hypotheses that have been put forward to explain the increased AMPAR responsiveness during LTP. We discuss the dynamic nature of AMPAR complexes, including their constant turnover and activity-dependent modifications that affect their synaptic accumulation. We highlight a hypothesis suggesting that AMPARs are diffusively trapped at synapses through activity-dependent interactions with protein-based binding slots in the post-synaptic density (PSD), offering a potential explanation for the increased synaptic strength during LTP. Furthermore, we outline the challenges still to be addressed before we fully understand the functional roles and molecular mechanisms of AMPAR dynamic nanoscale organization in LTP. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.

Chronic treatment with D2-antagonist haloperidol leads to inhibitory/excitatory imbalance in striatal D1-neurons.

Striatal dysfunction has been implicated in the pathophysiology of schizophrenia, a disorder characterized by positive symptoms such as hallucinations and delusions. Haloperidol is a typical antipsychotic medication used in the treatment of schizophrenia that is known to antagonize dopamine D2 receptors, which are abundantly expressed in the striatum. However, haloperidol's delayed therapeutic effect also suggests a mechanism of action that may go beyond the acute blocking of D2 receptors. Here, we performed proteomic analysis of striatum brain tissue and found more than 400 proteins significantly altered after 30 days of chronic haloperidol treatment in mice, namely proteins involved in glutamatergic and GABAergic synaptic transmission. Cell-type specific electrophysiological recordings further revealed that haloperidol not only reduces the excitability of striatal medium spiny neurons expressing dopamine D2 receptors (D2-MSNs) but also affects D1-MSNs by increasing the ratio of inhibitory/excitatory synaptic transmission (I/E ratio) specifically onto D1-MSNs but not D2-MSNs. Therefore, we propose the slow remodeling of D1-MSNs as a mechanism mediating the delayed therapeutic effect of haloperidol over striatum circuits. Understanding how haloperidol exactly contributes to treating schizophrenia symptoms may help to improve therapeutic outcomes and elucidate the molecular underpinnings of this disorder.

Integrated Design Fabrication and Control of a Bioinspired Multimaterial Soft Robotic Hand.

Machines that mimic humans have inspired scientists for centuries. Bioinspired soft robotic hands are a good example of such an endeavor, featuring intrinsic material compliance and continuous motion to deal with uncertainty and adapt to unstructured environments. Recent research led to impactful achievements in functional designs, modeling, fabrication, and control of soft robots. Nevertheless, the full realization of life-like movements is still challenging to achieve, often based on trial-and-error considerations from design to fabrication, consuming time and resources. In this study, a soft robotic hand is proposed, composed of soft actuator cores and an exoskeleton, featuring a multimaterial design aided by finite element analysis (FEA) to define the hand geometry and promote finger's bendability. The actuators are fabricated using molding, and the exoskeleton is 3D-printed in a single step. An ON-OFF controller keeps the set fingers' inner pressures related to specific bending angles, even in the presence of leaks. The FEA numerical results were validated by experimental tests, as well as the ability of the hand to grasp objects with different shapes, weights, and sizes. This integrated solution will make soft robotic hands more available to people, at a reduced cost, avoiding the time-consuming design-fabrication trial-and-error processes.

Molecular mechanisms of AMPAR reversible stabilization at synapses.

In the central nervous system, glutamatergic synapses play a central role in the regulation of excitatory neuronal transmission. With the membrane-associated guanylate kinase (MAGUK) family of proteins as their structuring scaffold, glutamatergic receptors serve as the powerhouse of glutamatergic synapses. Glutamatergic receptors can be categorized as metabotropic and ionotropic receptors. The latter are then categorized into N-methyl-d-aspartate, kainate receptors, and α-amino-3-hydroxy-5-methyl-isoxazole-propionic acid receptors (AMPARs). Over the past two decades, genetic tagging technology and super-resolution microscopy have been of the utmost importance to unravel how the different receptors are organized at glutamatergic synapses. At the plasma membrane, receptors are highly mobile but show reduced mobility when at synaptic sites. This partial immobilization of receptors at synaptic sites is attributed to the stabilization/anchoring of receptors with the postsynaptic MAGUK proteins and auxiliary proteins, and presynaptic proteins. These partial immobilizations and localization of glutamatergic receptors within the synaptic sites are fundamental for proper basal transmission and synaptic plasticity. Perturbations of the stabilization of glutamatergic receptors are often associated with cognitive deficits. In this review, we describe the proposed mechanisms for synaptic localization and stabilization of AMPARs, the major players of fast excitatory transmission in the central nervous system.

Analysis of ESAFORM 2021 cup drawing benchmark of an Al alloy, critical factors for accuracy and efficiency of FE simulations.

This article details the ESAFORM Benchmark 2021. The deep drawing cup of a 1 mm thick, AA 6016-T4 sheet with a strong cube texture was simulated by 11 teams relying on phenomenological or crystal plasticity approaches, using commercial or self-developed Finite Element (FE) codes, with solid, continuum or classical shell elements and different contact models. The material characterization (tensile tests, biaxial tensile tests, monotonic and reverse shear tests, EBSD measurements) and the cup forming steps were performed with care (redundancy of measurements). The Benchmark organizers identified some constitutive laws but each team could perform its own identification. The methodology to reach material data is systematically described as well as the final data set. The ability of the constitutive law and of the FE model to predict Lankford and yield stress in different directions is verified. Then, the simulation results such as the earing (number and average height and amplitude), the punch force evolution and thickness in the cup wall are evaluated and analysed. The CPU time, the manpower for each step as well as the required tests versus the final prediction accuracy of more than 20 FE simulations are commented. The article aims to guide students and engineers in their choice of a constitutive law (yield locus, hardening law or plasticity approach) and data set used in the identification, without neglecting the other FE features, such as software, explicit or implicit strategy, element type and contact model.

Effect of Residual Stresses on Fatigue Crack Growth: A Numerical Study Based on Cumulative Plastic Strain at the Crack Tip.

Residual stresses affect the fatigue behavior, given that compressive stresses delay the phenomenon, while tensile stresses accelerate it. However, the mechanisms behind the effect of residual stresses are not totally understood. A numerical study is developed here to understand the effect of thermal residual stresses (TRSs) on fatigue crack growth (FCG). The crack driving force was assumed to be the cumulative plastic strain at the crack tip. The heating of a region ahead of the crack tip produced elastic compressive TRS, which were 69% of material's yield stress. Alternatively, plastic deformation was produced by severe cooling followed by heating to generate compressive residual stresses. The crack propagation in the compressive residual stress field produced a decrease in the FCG rate. On the other hand, without the contact of crack flanks, the TRS showed no effect on FCG. Therefore, the TRSs only affect FCG by changing the crack closure level.

Bioorthogonal labeling of transmembrane proteins with non-canonical amino acids unveils masked epitopes in live neurons.

Progress in biological imaging is intrinsically linked to advances in labeling methods. The explosion in the development of high-resolution and super-resolution imaging calls for new approaches to label targets with small probes. These should allow to faithfully report the localization of the target within the imaging resolution - typically nowadays a few nanometers - and allow access to any epitope of the target, in the native cellular and tissue environment. We report here the development of a complete labeling and imaging pipeline using genetic code expansion and non-canonical amino acids in neurons that allows to fluorescently label masked epitopes in target transmembrane proteins in live neurons, both in dissociated culture and organotypic brain slices. This allows us to image the differential localization of two AMPA receptor (AMPAR) auxiliary subunits of the transmembrane AMPAR regulatory protein family in complex with their partner with a variety of methods including widefield, confocal, and dSTORM super-resolution microscopy.

FCG Modelling Considering the Combined Effects of Cyclic Plastic Deformation and Growth of Micro-Voids.

Fatigue is one of the most prevalent mechanisms of failure. Thus, the evaluation of the fatigue crack growth process is fundamental in engineering applications subjected to cyclic loads. The fatigue crack growth rate is usually accessed through the da/dN-ΔK curves, which have some well-known limitations. In this study a numerical model that uses the cyclic plastic strain at the crack tip to predict da/dN was coupled with the Gurson-Tvergaard-Needleman (GTN) damage model. The crack propagation process occurs, by node release, when the cumulative plastic strain reaches a critical value. The GTN model is used to account for the material degradation due to the growth of micro-voids process, which affects fatigue crack growth. Predictions with GTN are compared with the ones obtained without this ductile fracture model. Crack closure was studied in order to justify the lower values of da/dN obtained in the model with GTN, when compared with the results without GTN, for lower ΔK values. Finally, the accuracy of both variants of the numerical model is accessed through the comparison with experimental results.

Plasmalogens regulate the AKT-ULK1 signaling pathway to control the position of the axon initial segment.

The axon initial segment (AIS) is a specialized region in neurons that encompasses two essential functions, the generation of action potentials and the regulation of the axodendritic polarity. The mechanism controlling the position of the axon initial segment to allow plasticity and regulation of neuron excitability is unclear. Here we demonstrate that plasmalogens, the most abundant ether-phospholipid, are essential for the homeostatic positioning of the AIS. Plasmalogen deficiency is a hallmark of Rhizomelic Chondrodysplasia Punctata (RCDP) and Zellweger spectrum disorders, but Alzheimer's and Parkinson's disease, are also characterized by plasmalogen defects. Neurons lacking plasmalogens displaced the AIS to more distal positions and were characterized by reduced excitability. Treatment with a short-chain alkyl glycerol was able to rescue AIS positioning. Plasmalogen deficiency impaired AKT activation, and we show that inhibition of AKT phosphorylation at Ser473 and Thr308 is sufficient to induce a distal relocation of the AIS. Pathway analysis revealed that downstream of AKT, overtly active ULK1 mediates AIS repositioning. Rescuing the impaired AKT signaling pathway was able to normalize AIS position independently of the biochemical defect. These results unveil a previously unknown mechanism that couples the phospholipid composition of the neuronal membrane to the positional assembly of the AIS.

Revisiting Classical Issues of Fatigue Crack Growth Using a Non-Linear Approach.

Fatigue crack growth (FCG) has been studied for decades; however, several aspects are still objects of controversy. The objective here is to discuss different issues, using a numerical approach based on crack tip plastic strain, assuming that FCG is driven by crack tip deformation. ΔK was found to control cyclic plastic deformation at the crack tip, while Kmax has no effect. Therefore, alternative mechanisms are required to justify models based on ΔK and Kmax. The analysis of crack tip plastic deformation also showed that there is crack tip damage below crack closure. Therefore, the definition of an effective load range ΔKeff = Kmax - Kopen is not correct, because the portion of load range below opening also contributes to FCG. Below crack closure, damage occurs during unloading while during loading the crack tip deformation is elastic. However, if the maximum load is decreased below the elastic limit, which corresponds to the transition between elastic and elasto-plastic regimes, there is no crack tip damage. Additionally, a significant effect of the crack ligament on crack closure was found in tests with different crack lengths and the same ΔK. Finally, the analysis of FCG after an overload with and without contact of crack flanks showed that the typical variation of da/dN observed is linked to crack closure variations, while the residual stresses ahead of crack tip are not affected by the contact of crack flanks.

Leukodystrophy caused by plasmalogen deficiency rescued by glyceryl 1-myristyl ether treatment.

Plasmalogens are the most abundant form of ether phospholipids in myelin and their deficiency causes Rhizomelic Chondrodysplasia Punctata (RCDP), a severe developmental disorder. Using the Gnpat-knockout (KO) mouse as a model of RCDP, we determined the consequences of a plasmalogen deficiency during myelination and myelin homeostasis in the central nervous system (CNS). We unraveled that the lack of plasmalogens causes a generalized hypomyelination in several CNS regions including the optic nerve, corpus callosum and spinal cord. The defect in myelin content evolved to a progressive demyelination concomitant with generalized astrocytosis and white matter-selective microgliosis. Oligodendrocyte precursor cells (OPC) and mature oligodendrocytes were abundant in the CNS of Gnpat KO mice during the active period of demyelination. Axonal loss was minimal in plasmalogen-deficient mice, although axonal damage was observed in spinal cords from aged Gnpat KO mice. Characterization of the plasmalogen-deficient myelin identified myelin basic protein and septin 7 as early markers of dysmyelination, whereas myelin-associated glycoprotein was associated with the active demyelination phase. Using in vitro myelination assays, we unraveled that the intrinsic capacity of oligodendrocytes to ensheath and initiate membrane wrapping requires plasmalogens. The defect in plasmalogens was rescued with glyceryl 1-myristyl ether [1-O-tetradecyl glycerol (1-O-TDG)], a novel alternative precursor in the plasmalogen biosynthesis pathway. 1-O-TDG treatment rescued myelination in plasmalogen-deficient oligodendrocytes and in mutant mice. Our results demonstrate the importance of plasmalogens for oligodendrocyte function and myelin assembly, and identified a novel strategy to promote myelination in nervous tissue.

GPER: A new tool to protect dopaminergic neurons?

Parkinson's disease (PD) is characterized by a selective degeneration of nigrostriatal dopaminergic pathway. Epidemiological studies revealed a male predominance of the disease that has been attributed to the female steroid hormones, mainly the estrogen. Estrogen neuroprotective effects have been shown in several studies, however the mechanisms responsible by these effects are still unclear. Previous data from our group revealed that glial cell line-derived neurotrophic factor (GDNF) is crucial to the dopaminergic protection provided by 17ß-estradiol, and also suggest that the intracellular estrogen receptors (ERs) are not required for that neuroprotective effects. The present study aimed to investigate the contribution of the G protein-coupled ER (GPER) activation in estrogen-mediated dopaminergic neuroprotection against an insult induced by 1-methyl-4-phenylpyridinium (MPP(+)), and whether GPER neuroprotective effects involve the regulation of GDNF expression. Using primary mesencephalic cultures, we found that GPER activation protects dopaminergic neurons from MPP(+) toxicity in an extent similar to the promoted by a 17ß-estradiol. Moreover, GPER activation promotes an increase in GDNF levels. Both, GDNF antibody neutralization or RNA interference-mediated GDNF knockdown prevented the GPER-mediated dopaminergic protection verified in mesencephalic cultures challenged with MPP(+). Overall, these results revealed that G1, a selective agonist of GPER, is able to protect dopaminergic neurons and that GDNF overexpression is a key feature to GPER induced the neuroprotective effects.

Influência do clima como desencadeante de crises de enxaqueca: estudo prospectivo / Influence of climate as triggering factor of migraine crises: prospective study

JUSTIFICATIVA E OBJETIVOS: Enxaqueca é uma cefaleia primária altamente prevalente, afetando a qualidade de vida dos pacientes. Pode começar na infância ou adolescência e acompanhar o paciente por toda a sua vida. Os fatores desencadeantes das crises de enxaqueca, quando identificados, podem auxiliar o paciente a lidar com os estímulos externos e levar ao tratamento mais eficaz. O objetivo deste estudo foi observar se as alterações climáticas da região podem ser um potencial fator desencadeante de crises de enxaqueca. MÉTODO: Estudo prospectivo incluindo 60 pacientes que apresentam enxaqueca e moram na cidade de Santos, SP, Brasil. Os participantes foram selecionados de acordo com os critérios diagnósticos de enxaqueca da International Headache Society. Os dados dos diários de cefaleia foram correlacionados com as informações fornecidas pelo Climatempo Santos. RESULTADOS: Quarenta e nove diários de cefaleia abrangendo 104 dias de avaliação prospectiva foram devolvidos e analisados. Durante os 104 dias de estudo, foram registradas crises de enxaqueca em 96 dias (92,3%). Em 51 dias 10% ou mais dos participantes (> 5) apresentaram crises de enxaqueca, enquanto em sete dias 20% ou mais dos participantes (> 10) tiveram crise de enxaqueca. A umidade do ar foi praticamente 50% menor na véspera dos dias de maior incidência de crises de enxaqueca (p < 0,001), quando também se observou menor pressão relativa do ar (p = 0,01). CONCLUSÃO: Foi observada correlação entre a baixa pressão atmosférica e a baixa umidade do ar com a prevalência de crises de enxaqueca no dia seguinte.

BACKGROUND AND OBJECTIVES: Migraine is a highly prevalent primary headache affecting patients' quality of life. It may start in childhood or adolescence and follow patients throughout their lives. Triggering migraine crises factors, when identified, may help patients cope with external stimuli and may lead to a more effective treatment. This study aimed at observing whether climate changes in the region may be a potential triggering factor for migraine crises. METHOD: Prospective study including 60 migraine patients living in the city of Santos, SP, Brazil. Participants were selected according to migraine diagnostic criteria of the International Headache Society. Headache diary data were correlated to information supplied by Climatempo Santos. RESULTS: Forty-nine headache diaries comprising 104 days of prospective evaluation were developed and analyzed. Migraine crises were recorded in 96 days (92.3%). In 51 days, 10% or more of participants (> 5) presented migraine crises while in seven days 20% or more of participants (> 10) had migraine crises. Relative humidity was approximately 50% lower the day before the days of higher incidence of migraine crises (p < 0.001), when lower relative air pressure was also observed (p = 0.01). CONCLUSION: There has been correlation between low air pressure and low relative humidity and the prevalence of migraine crises the day after.

Prevalence of open angle glaucoma in accompanying first degree relatives of patients with glaucoma.

OBJECTIVE: The aim of this study was to determine the prevalence of open angle glaucoma in first-degree relatives accompanying POAG patients during routine examination in a reference hospital. METHOD: First-degree relatives of primary open angle glaucoma patients who accompanied their relatives to the glaucoma service of a reference hospital were screened for glaucoma. RESULTS: One-hundred and one first-degree relatives were examined, of which 56.4% had never had their intraocular pressure measured. 10.9% had previously been diagnosed with glaucoma, and 5.9% were newly diagnosed during this study. CONCLUSIONS: The eye examination of first-degree relatives identified a significant percentage of individuals with glaucoma. Despite being first-degree relatives of glaucoma patients, 56.4% of the companions had never had their eye pressure measured, demonstrating a lack of awareness about this disease.

Prevalence of open angle glaucoma in accompanying first degree relatives of patients with glaucoma

OBJECTIVE: The aim of this study was to determine the prevalence of open angle glaucoma in first-degree relatives accompanying POAG patients during routine examination in a reference hospital. METHOD: First-degree relatives of primary open angle glaucoma patients who accompanied their relatives to the glaucoma service of a reference hospital were screened for glaucoma. RESULTS: One-hundred and one first-degree relatives were examined, of which 56.4 percent had never had their intraocular pressure measured. 10.9 percent had previously been diagnosed with glaucoma, and 5.9 percent were newly diagnosed during this study. CONCLUSIONS: The eye examination of first-degree relatives identified a significant percentage of individuals with glaucoma. Despite being first-degree relatives of glaucoma patients, 56.4 percent of the companions had never had their eye pressure measured, demonstrating a lack of awareness about this disease.

Restaurações diretas no Programa Saúde da Família em Teresina (PI) / Direct restorations in the family health program in Teresina (PI)

Objetivos: Traçar o perfil da odontologia restauradora realizada por essas Equipes de Saúde Bucal. Métodos: Realizou-se um levantamento das características dos procedimentos restauradores diretos realizados pelas Equipes de Saúde Bucal do Programa Saúde da Família em Teresina, Piauí, por meio de um formulário de coleta de dados entregue aos dentistas participantes. Resultados: Um total de 2027 dados sobre procedimentos restauradores diretos foi coletado, dos quais 1527 (75,33%) foram restaurações novas, 406 (20,03%) foram substituições, sendo 325 (16,03%) pelo mesmo material restaurador e 81 (4%) por outro material restaurador, 94 (4,64%) foram devido a outros procedimentos. O material restaurador mais utilizado foi o amálgama em 1119 (55,20%) procedimentos realizados, seguido de resina composta em 837 (41,29%) e ionômero de vidro em 71 (3,50%). Os principais motivos foram cárie primária com 1423 (70,20%) procedimentos, seguido por 242 (11,94%) de fratura de restauração, 226 (11,15%) de lesão de cárie recorrente ou recidiva de cárie, 57 (2,81 %) de lesões cervicais, 43 (2,12%) de alteração de cor, 41 (2,02%), fratura do dente, 12 (0,59%) de hipoplasia e 2 (0,10%) por outros motivos. As substituições de restaurações usando o mesmo material restaurador tiveram como motivo principal a fratura da restauração; já as substituições por outro material tiveram a recidiva de cárie como principal motivo. Por sua vez, as restaurações novas tiveram como motivo principal lesões de cárie primárias. Houve associação estatisticamente significante (p<0,05) entre dente acometido pelo procedimento e material restaurador, superfície dentária e material restaurador, e, procedimento e material restaurador. Conclusão: De acordo com a metodologia utilizada e com a análise dos resultados, conclui-se que: o amálgama é o material restaurador mais utilizado; a maioria dos procedimentos realizados corresponde à colocação de novas restaurações e a causa mais comum para realização destes...