G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling.

Ras GTPase-activating protein-binding proteins 1 and 2 (G3BP1 and G3BP2, respectively) are widely recognized as core components of stress granules (SGs). We report that G3BPs reside at the cytoplasmic surface of lysosomes. They act in a non-redundant manner to anchor the tuberous sclerosis complex (TSC) protein complex to lysosomes and suppress activation of the metabolic master regulator mechanistic target of rapamycin complex 1 (mTORC1) by amino acids and insulin. Like the TSC complex, G3BP1 deficiency elicits phenotypes related to mTORC1 hyperactivity. In the context of tumors, low G3BP1 levels enhance mTORC1-driven breast cancer cell motility and correlate with adverse outcomes in patients. Furthermore, G3bp1 inhibition in zebrafish disturbs neuronal development and function, leading to white matter heterotopia and neuronal hyperactivity. Thus, G3BPs are not only core components of SGs but also a key element of lysosomal TSC-mTORC1 signaling.

Structure of the lysosomal mTORC1-TFEB-Rag-Ragulator megacomplex.

The transcription factor TFEB is a master regulator of lysosomal biogenesis and autophagy1. The phosphorylation of TFEB by the mechanistic target of rapamycin complex 1 (mTORC1)2-5 is unique in its mTORC1 substrate recruitment mechanism, which is strictly dependent on the amino acid-mediated activation of the RagC GTPase activating protein FLCN6,7. TFEB lacks the TOR signalling motif responsible for the recruitment of other mTORC1 substrates. We used cryogenic-electron microscopy to determine the structure of TFEB as presented to mTORC1 for phosphorylation, which we refer to as the 'megacomplex'. Two full Rag-Ragulator complexes present each molecule of TFEB to the mTOR active site. One Rag-Ragulator complex is bound to Raptor in the canonical mode seen previously in the absence of TFEB. A second Rag-Ragulator complex (non-canonical) docks onto the first through a RagC GDP-dependent contact with the second Ragulator complex. The non-canonical Rag dimer binds the first helix of TFEB with a RagCGDP-dependent aspartate clamp in the cleft between the Rag G domains. In cellulo mutation of the clamp drives TFEB constitutively into the nucleus while having no effect on mTORC1 localization. The remainder of the 108-amino acid TFEB docking domain winds around Raptor and then back to RagA. The double use of RagC GDP contacts in both Rag dimers explains the strong dependence of TFEB phosphorylation on FLCN and the RagC GDP state.

Truncated variants of MAGEL2 are involved in the etiologies of the Schaaf-Yang and Prader-Willi syndromes.

The neurodevelopmental disorders Prader-Willi syndrome (PWS) and Schaaf-Yang syndrome (SYS) both arise from genomic alterations within human chromosome 15q11-q13. A deletion of the SNORD116 cluster, encoding small nucleolar RNAs, or frameshift mutations within MAGEL2 result in closely related phenotypes in individuals with PWS or SYS, respectively. By investigation of their subcellular localization, we observed that in contrast to a predominant cytoplasmic localization of wild-type (WT) MAGEL2, a truncated MAGEL2 mutant was evenly distributed between the cytoplasm and the nucleus. To elucidate regulatory pathways that may underlie both diseases, we identified protein interaction partners for WT or mutant MAGEL2, in particular the survival motor neuron protein (SMN), involved in spinal muscular atrophy, and the fragile-X-messenger ribonucleoprotein (FMRP), involved in autism spectrum disorders. The interactome of the non-coding RNA SNORD116 was also investigated by RNA-CoIP. We show that WT and truncated MAGEL2 were both involved in RNA metabolism, while regulation of transcription was mainly observed for WT MAGEL2. Hence, we investigated the influence of MAGEL2 mutations on the expression of genes from the PWS locus, including the SNORD116 cluster. Thereby, we provide evidence for MAGEL2 mutants decreasing the expression of SNORD116, SNORD115, and SNORD109A, as well as protein-coding genes MKRN3 and SNRPN, thus bridging the gap between PWS and SYS.

A substrate-specific mTORC1 pathway underlies Birt-Hogg-Dubé syndrome.

The mechanistic target of rapamycin complex 1 (mTORC1) is a key metabolic hub that controls the cellular response to environmental cues by exerting its kinase activity on multiple substrates1-3. However, whether mTORC1 responds to diverse stimuli by differentially phosphorylating specific substrates is poorly understood. Here we show that transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy4,5, is phosphorylated by mTORC1 via a substrate-specific mechanism that is mediated by Rag GTPases. Owing to this mechanism, the phosphorylation of TFEB-unlike other substrates of mTORC1, such as S6K and 4E-BP1- is strictly dependent on the amino-acid-mediated activation of RagC and RagD GTPases, but is insensitive to RHEB activity induced by growth factors. This mechanism has a crucial role in Birt-Hogg-Dubé syndrome, a disorder that is caused by mutations in the RagC and RagD activator folliculin (FLCN) and is characterized by benign skin tumours, lung and kidney cysts and renal cell carcinoma6,7. We found that constitutive activation of TFEB is the main driver of the kidney abnormalities and mTORC1 hyperactivity in a mouse model of Birt-Hogg-Dubé syndrome. Accordingly, depletion of TFEB in kidneys of these mice fully rescued the disease phenotype and associated lethality, and normalized mTORC1 activity. Our findings identify a mechanism that enables differential phosphorylation of mTORC1 substrates, the dysregulation of which leads to kidney cysts and cancer.

Metal encapsulation of waste foundry sand stabilized with alkali-activated binder: Batch and column leaching tests.

Waste stabilization processes are important to add value and reduce environmental risks related to metal contamination of soils and groundwater. This study evaluated the metal encapsulation of: (i) waste foundry sand (WFS) stabilized with an alkali-activated binder (AAB), compared to (ii) WFS-Portland cement (PC) mixture. The AAB was composed by sugar cane bagasse ash (SCBA), hydrated eggshell lime, and sodium hydroxide solution. The metal leaching behavior from WFS-AAB and WFS-PC was investigated through batch and column tests according to NBR 10005 and ASTM D4874 methods, respectively. All WFS-AAB and WFS-PC mixtures showed no metal toxicity. WFS-AAB matrices encapsulated the heavy metals Cd, Cr, and Pb from WFS and SCBA. Leaching results from NBR 10005 method were more favorable than ASTM D4874 for water quality limits (CONAMA 460, Dutch List, and EPA). Binder type, metals leaching patterns, and leaching test procedures were key factors in understanding the environmental performance of cemented WFS.

Lysosomal size matters.

Lysosomes are key cellular catabolic centers that also perform fundamental metabolic, signaling and quality control functions. Lysosomes are not static and they respond dynamically to intra- and extracellular stimuli triggering changes in organelle numbers, size and position. Such physical changes have a strong impact on lysosomal activity ultimately influencing cellular homeostasis. In this review, we summarize the current knowledge on lysosomal size regulation, on its physiological role(s) and association to several disease conditions.

Stainless steel crown vs bulk fill composites for the restoration of primary molars post-pulpectomy: 1-year survival and acceptance results of a randomized clinical trial.

BACKGROUND: A key factor for the success and longevity of the endodontic treatment is sealing of the cavity after restorative treatment. AIM: The aim of this randomised clinical trial was to evaluate the 1-year survival of endodontic treatment in primary molars restored with stainless steel crowns (SSCs) and bulk fill composite resin (BF). As a secondary outcome, the acceptance of both children and parents was evaluated. DESIGN: Ninety-one 3- to 8-year-old children with at least one primary molar requiring endodontic treatment were selected. Participants were randomized to SSC or BF and evaluated after 1, 3, 6, and 12 months. An acceptance questionnaire was completed immediately after the treatment. The primary outcome was the endodontic treatment success, evaluated in the intention-to-treat (ITT) population using the Kaplan-Meier and non-inferiority Cox regression analyses, with a non-inferiority limit of 15%. Sensitivity analysis between the success rates after 1 year was performed using Miettinen-Nurminen's method. The Mann-Whitney test was used to compare the treatment acceptance (α = 5%). RESULTS: The survival rate after 1 year was BF = 75% and SSC = 88% (HR = 1.41; 90% CI 0.57-3.43). ITT analysis showed a success rate of BF = 86.7% and SSC = 82.6% (RR = 0.95; 0.78-1.16). The non-inferiority hypothesis between the survival of endodontic treatment could not be proved in both analyses (P > .05). The overall acceptance scores did not differ between the restorative groups (P > .05). CONCLUSION: This study failed to show non-inferiority of BF compared with the SSC. The materials were well accepted by both children and their parents.

SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1.

Cell growth and proliferation are tightly linked to nutrient availability. The mechanistic target of rapamycin complex 1 (mTORC1) integrates the presence of growth factors, energy levels, glucose and amino acids to modulate metabolic status and cellular responses. mTORC1 is activated at the surface of lysosomes by the RAG GTPases and the Ragulator complex through a not fully understood mechanism monitoring amino acid availability in the lysosomal lumen and involving the vacuolar H(+)-ATPase. Here we describe the uncharacterized human member 9 of the solute carrier family 38 (SLC38A9) as a lysosomal membrane-resident protein competent in amino acid transport. Extensive functional proteomic analysis established SLC38A9 as an integral part of the Ragulator-RAG GTPases machinery. Gain of SLC38A9 function rendered cells resistant to amino acid withdrawal, whereas loss of SLC38A9 expression impaired amino-acid-induced mTORC1 activation. Thus SLC38A9 is a physical and functional component of the amino acid sensing machinery that controls the activation of mTOR.

Development of a secondary school-based digital behaviour change intervention to improve tooth brushing.

BACKGROUND: Dental caries in adolescents remains a significant public health problem with few oral health promotion interventions aimed at reducing dental caries in secondary school-aged students. Previous oral health and mobile health (mHealth) research has suggested the need for the development of a school-based behaviour change intervention incorporating a digital component. This study aimed to describe the development process of a behaviour change intervention to improve the oral health of students aged 11-16 years attending secondary schools in the UK. METHODS: A six-step process was used to develop the complex intervention informed by behaviour change theory and involving students, young people, parents and teachers in the process. The steps were: (1) identifying the target behaviours, namely tooth brushing with a fluoride toothpaste (2) identifying the theoretical basis and developing the causal model (3) reviewing the relevant literature and developing the logic model (4) designing the intervention with young people, parents and school staff (5) specifying the intervention content and (6) translating this content into features of the intervention and piloting. RESULTS: The resultant intervention included a quality-assured classroom-based session (CBS) (guided by a lesson plan and teaching resources), delivered by school teachers which was embedded within the school curriculum. This CBS was followed by a series of (Short Message Service) SMS texts delivered twice daily to student's mobile telephones with the content, duration and timing of the messages informed by involvement of students and young people. CONCLUSIONS: An intervention to improve the oral health of secondary school students through improved tooth brushing was rigorously developed based on behaviour change theory and work with young people, parents and school staff. Further research is needed to evaluate the outcomes and processes involved following the delivery of this intervention. BRIGHT Trial Trial Registration ISRCTN12139369.

Combining high-pressure freezing with pre-embedding immunogold electron microscopy and tomography.

Immunogold labeling of permeabilized whole-mount cells or thin-sectioned material is widely used for the subcellular localization of biomolecules at the high spatial resolution of electron microscopy (EM). Those approaches are well compatible with either 3-dimensional (3D) reconstruction of organelle morphology and antigen distribution or with rapid cryofixation-but not easily with both at once. We describe here a specimen preparation and labeling protocol for animal cell cultures, which represents a novel blend of specifically adapted versions of established techniques. It combines the virtues of reliably preserved organelle ultrastructure, as trapped by rapid freezing within milliseconds followed by freeze-substitution and specimen rehydration, with the advantages of robust labeling of intracellular constituents in 3D through means of pre-embedding NANOGOLD-silver immunocytochemistry. So obtained thin and semi-thick epoxy resin sections are suitable for transmission EM imaging, as well as tomographic reconstruction and modeling of labeling patterns in the 3D cellular context.

Dental caries experience, care index and restorative index in children with learning disabilities and children without learning disabilities; a systematic review and meta-analysis.

BACKGROUND: Children with learning disabilities (CLD) have worse health outcomes than children with no learning disabilities (CNLD). This systematic review compared caries experience and met dental care need for CLD to CNLD using Decayed, Missing, Filled Permanent Teeth (DMFT) and decayed, missing/extracted, filled primary teeth (dmft/deft), care index (CI), and restorative index (RI) values. METHODS: Without date or language restrictions four databases were searched for; cross-sectional studies comparing caries experience and CI/ RI in CLD matched to groups of CNLD. Screening and data extraction were carried out independently and in duplicate. Risk of bias was assessed using the Newcastle-Ottawa Scale. Meta-analyses were carried out (random effects model). RESULTS: There were 25 articles with 3976 children (1 to 18 years old), from 18 countries, fitting the inclusion criteria. Children with; Down syndrome were investigated in 11 studies, autism in 8 and mixed learning disabilities in 6. The overall mean DMFT for CLD was 2.31 (standard deviation±1.97; range 0.22 to 7.2) and for CNLD was 2.51 (±2.14; 0.37 to 4.76). Using standardised mean difference (SMD), meta-analysis showed no evidence of a difference between CLD and CNLD (n = 16 studies) for caries experience (SMD = -0.43; 95%CI = -0.91 to 0.05). This was similar for sub-groups of children with autism (SMD = -0.28; 95%CI = 1.31 to 0.75) and mixed disabilities (SMD = 0.26; 95%CI = -0.94 to 1.47). However, for children with Down syndrome, caries experience was lower for CLD than CNLD (SMD = -0.73; 95%CI = -1.28 to - 0.18). For primary teeth, mean dmft/deft was 2.24 for CLD and 2.48 for CNLD (n = 8 studies). Meta-analyses showed no evidence of a difference between CLD and CNLD for caries experience across all disability groups (SMD = 0.41; 95% CI = -0.14 to 0.96), or in sub-groups: Down syndrome (SMD = 0.55; 95%CI- = - 0.40 to 1.52), autism (SMD = 0.43; 95%CI = -0.53 to 2.39) and mixed disabilities (SMD = -0.10; 95%CI = -0.34 to 0.14). The studies' risk of bias were medium to high. CONCLUSION: There was no evidence of a difference in caries levels in primary or permanent dentitions for CLD and CNLD. This was similar for learning disability sub-groups, except for Down syndrome where dental caries levels in permanent teeth was lower. Data on met need for dental caries was inconclusive. TRIAL REGISTRATION: The protocol was published in PROSPERO: CRD42017068964 (June 8th, 2017).

A novel but frequent variant in LPA KIV-2 is associated with a pronounced Lp(a) and cardiovascular risk reduction.

AIMS: Lp(a) concentrations represent a major cardiovascular risk factor and are almost entirely controlled by one single locus (LPA). However, many genetic factors in LPA governing the enormous variance of Lp(a) levels are still unknown. Since up to 70% of the LPA coding sequence are located in a difficult to access hypervariable copy number variation named KIV-2, we hypothesized that it may contain novel functional variants with pronounced effects on Lp(a) concentrations. We performed a large scale mutation analysis in the KIV-2 using an extreme phenotype approach. METHODS AND RESULTS: We compiled an discovery set of 123 samples showing discordance between LPA isoform phenotype and Lp(a) concentrations and controls. Using ultra-deep sequencing, we identified a splice site variant (G4925A) in preferential association with the smaller LPA isoforms. Follow-up in a European general population (n = 2892) revealed an exceptionally high carrier frequency of 22.1% in the general population. The variant explains 20.6% of the Lp(a) variance in carriers of low molecular weight (LMW) apo(a) isoforms (P = 5.75e-38) and reduces Lp(a) concentrations by 31.3 mg/dL. Accordingly the odds ratio for cardiovascular disease was reduced from 1.39 [95% confidence interval (CI): 1.17-1.66, P = 1.89e-04] for wildtype LMW individuals to 1.19 [95%CI: 0.92; 1.56, P = 0.19] in LMW individuals who were additionally positive for G4925A. Functional studies point towards a reduction of splicing efficiency by this novel variant. CONCLUSION: A highly frequent but until now undetected variant in the LPA KIV-2 region is strongly associated with reduced Lp(a) concentrations and reduced cardiovascular risk in LMW individuals.

OBAT: An open-source and low-cost operant box for auditory discriminative tasks.

Operant-conditioning boxes are widely used in animal training, allowing researchers to shape specific behaviors through reinforcements and/or punishments. Commercially available devices are expensive and run with proprietary software and hardware, hampering adaptations for the specific needs of an experiment. Therefore, many low-cost and open-source devices have recently been developed, but there are still few options for studying auditory behaviors. To overcome this problem, we developed a device based on a computer and an Arduino Mega 2560 board, named OBAT (Operant Box for Auditory Tasks), designed to present two different auditory stimuli to small primates. It has three modules: sound delivery, response bars, and reward system. We estimate that OBAT is at least 4-10 times cheaper than commercially available operant-conditioning boxes. Data from a behavioral pilot test ensured that the device can be used to train a marmoset in an auditory discrimination task. In addition, despite its low cost, accuracy tests showed that the OBAT operates with a high temporal precision. All schematics and software source code are available so that other groups can easily replicate the experiment or adapt the device to their own needs.

Ultrastructural Morphometry Points to a New Role for LAMTOR2 in Regulating the Endo/Lysosomal System.

The late endosomal adaptor protein LAMTOR2/p14 is essential for tissue homeostasis by controlling MAPK and mTOR signaling, which in turn regulate cell growth and proliferation, migration and spreading. Moreover, LAMTOR2 critically controls architecture and function of the endocytic system, including epidermal growth factor receptor (EGFR) degradation in lysosomes, positioning of late endosomes and defense against intracellular pathogens. Here we describe the multifaceted ultrastructural phenotype of the endo/lysosomal system of LAMTOR2-deficient mouse embryonic fibroblasts. Quantitative (immuno-)electron microscopy of cryo-fixed samples revealed significantly reduced numbers of recycling tubules emanating from maturing multivesicular bodies (MVB). Instead, a distinct halo of vesicles surrounded MVB, tentatively interpreted as detached, jammed recycling tubules. These morphological changes in LAMTOR2-deficient cells correlated with the presence of growth factors (e.g. EGF), but were similarly induced in control cells by inactivating mTOR. Furthermore, proper transferrin receptor trafficking and recycling were apparently dependent on an intact LAMTOR complex. Finally, a severe imbalance in the relative proportions of endo/lysosomes was found in LAMTOR2-deficient cells, resulting from increased amounts of mature MVB and (autophago)lysosomes. These observations suggest that the LAMTOR/Ragulator complex is required not only for maintaining the homeostasis of endo/lysosomal subpopulations but also contributes to the proper formation of MVB-recycling tubules, and regulation of membrane/cargo recycling from MVB.

Stability of the endosomal scaffold protein LAMTOR3 depends on heterodimer assembly and proteasomal degradation.

LAMTOR3 (MP1) and LAMTOR2 (p14) form a heterodimer as part of the larger Ragulator complex that is required for MAPK and mTOR1 signaling from late endosomes/lysosomes. Here, we show that loss of LAMTOR2 (p14) results in an unstable cytosolic monomeric pool of LAMTOR3 (MP1). Monomeric cytoplasmic LAMTOR3 is rapidly degraded in a proteasome-dependent but lysosome-independent manner. Mutational analyses indicated that the turnover of the protein is dependent on ubiquitination of several lysine residues. Similarly, other Ragulator subunits, LAMTOR1 (p18), LAMTOR4 (c7orf59), and LAMTOR5 (HBXIP), are degraded as well upon the loss of LAMTOR2. Thus the assembly of the Ragulator complex is monitored by cellular quality control systems, most likely to prevent aberrant signaling at the convergence of mTOR and MAPK caused by a defective Ragulator complex.

Malaria in Brazil: what happens outside the Amazonian endemic region.

Brazil, a country of continental proportions, presents three profiles of malaria transmission. The first and most important numerically, occurs inside the Amazon. The Amazon accounts for approximately 60% of the nation's territory and approximately 13% of the Brazilian population. This region hosts 99.5% of the nation's malaria cases, which are predominantly caused by Plasmodium vivax (i.e., 82% of cases in 2013). The second involves imported malaria, which corresponds to malaria cases acquired outside the region where the individuals live or the diagnosis was made. These cases are imported from endemic regions of Brazil (i.e., the Amazon) or from other countries in South and Central America, Africa and Asia. Imported malaria comprised 89% of the cases found outside the area of active transmission in Brazil in 2013. These cases highlight an important question with respect to both therapeutic and epidemiological issues because patients, especially those with falciparum malaria, arriving in a region where the health professionals may not have experience with the clinical manifestations of malaria and its diagnosis could suffer dramatic consequences associated with a potential delay in treatment. Additionally, because the Anopheles vectors exist in most of the country, even a single case of malaria, if not diagnosed and treated immediately, may result in introduced cases, causing outbreaks and even introducing or reintroducing the disease to a non-endemic, receptive region. Cases introduced outside the Amazon usually occur in areas in which malaria was formerly endemic and are transmitted by competent vectors belonging to the subgenus Nyssorhynchus (i.e., Anopheles darlingi, Anopheles aquasalis and species of the Albitarsis complex). The third type of transmission accounts for only 0.05% of all cases and is caused by autochthonous malaria in the Atlantic Forest, located primarily along the southeastern Atlantic Coast. They are caused by parasites that seem to be (or to be very close to) P. vivax and, in a less extent, by Plasmodium malariae and it is transmitted by the bromeliad mosquito Anopheles (Kerteszia) cruzii. This paper deals mainly with the two profiles of malaria found outside the Amazon: the imported and ensuing introduced cases and the autochthonous cases. We also provide an update regarding the situation in Brazil and the Brazilian endemic Amazon.

Environmental, economic, and social impacts of sugar cane bagasse and eggshell wastes for soil stabilization.

Sustainability is a core topic for all sectors including geotechnical engineering (e.g., design of foundations, earthworks structures, and pavements for major infrastructure and building projects). Despite being comprised of environmental, economic, and social pillars, most sustainability studies in this area have focused on the first. Furthermore, social impacts and the three pillars integration are little explored. As a result, there is a lack of systemic and holistic assessments of innovative geotechnical alternatives. This research advances in this area by performing a complete sustainability assessment and integration of the environmental, economic, and social pillars of two expansive soil stabilization alternatives: (i) sugar cane bagasse ash combined with hydrated eggshell lime alkali-activated by sodium hydroxide (NaOH) and (ii) Portland cement. Individual analyses were carried out to determine the environmental, economic, and social impacts, and the single sustainability index. Alkali-activated binder dosages showed higher impacts in 4 out of 10 environmental categories. For both binders, high-density/low-binder dosages contributed to environmental and economic sustainability as they require lower quantities of raw materials and diesel for materials transportation. The total costs of alkali-activated binder dosages ($189.79 and $154.45) were higher than that of Portland cement ($72.49 and $54.04), mainly due to the high cost of NaOH acquisition. However, the alkali-activated binder dosages implied lower carbon dioxide (CO2) emissions and thus lower social cost of CO2. The alternative binder presented a higher positive social impact. The alkali-activated high-density/low binder dosage is the most sustainable soil stabilization strategy.

Neuronal responses in the nucleus accumbens shell during sexual behavior in male rats.

Previous behavioral studies have indicated that the nucleus accumbens (NAc) shell of a male rat is involved in its sexual behavior; however, no previous studies have investigated neuronal activities in the male rat NAc shell during sexual behavior. To investigate this issue, we recorded single unit activities in the NAc shell of male rats during sexual behavior. Of 123 NAc shell neurons studied, 53, 47, and 40 neurons exhibited significantly changed firing rates at various times during intromission, genital auto-grooming, and sniffing of females, respectively. The two types of NAc shell neurons [putative fast spiking interneurons (pFSIs) and medium spiny neurons (pMSNs)] responded differently during sexual behavior. First, more pFSIs than pMSNs exhibited inhibitory responses to thrusting with intromission and genital grooming, while pFSIs and pMSNs responded similarly to sniffing of females. Second, both pFSIs and pMSNs responded differently to thrusting with and without intromission. Furthermore, NAc shell neuronal activity was significantly different across the different phases of sexual behavior, and the number of NAc shell neurons with delta oscillation, which is related to behavioral inhibition, and high gamma oscillation, which is related to reward perception, increased after ejaculation. Together, our results suggest that the NAc shell is deeply involved in sexual behavior, and changes in NAc shell neuronal activity are related to performance of sexual behavior, encoding cues or contexts related to sexual behavior, reward-related processing, and the inhibition of sexual behavior after ejaculation.

An Integrated Neurorobotics Model of the Cerebellar-Basal Ganglia Circuitry.

This work presents a neurorobotics model of the brain that integrates the cerebellum and the basal ganglia regions to coordinate movements in a humanoid robot. This cerebellar-basal ganglia circuitry is well known for its relevance to the motor control used by most mammals. Other computational models have been designed for similar applications in the robotics field. However, most of them completely ignore the interplay between neurons from the basal ganglia and cerebellum. Recently, neuroscientists indicated that neurons from both regions communicate not only at the level of the cerebral cortex but also at the subcortical level. In this work, we built an integrated neurorobotics model to assess the capacity of the network to predict and adjust the motion of the hands of a robot in real time. Our model was capable of performing different movements in a humanoid robot by respecting the sensorimotor loop of the robot and the biophysical features of the neuronal circuitry. The experiments were executed in simulation and the real world. We believe that our proposed neurorobotics model can be an important tool for new studies on the brain and a reference toward new robot motor controllers.