Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 126
Filtrar
1.
Immunobiology ; : 151935, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32201093

RESUMO

Macrophages are essential components of the immune system. Macrophages can be derived from the bone marrow of mice with either recombinant M-CSF or L929 supernatant. Recent literature considers recombinant M-CSF- and L929-derived macrophages as equals, even though L929-derived macrophages are exposed to other substances secreted in the L929 supernatant, and not only M-CSF. Thus, we decided to perform a comparative analysis of both inflammatory and metabolic profiles of macrophages differentiated under the aforementioned conditions, which is relevant for standardization and interpretation of in vitro studies. We observed that, when treated with LPS, L929macs secrete lower levels of proinflammatory cytokines (TNF-α, IL-6, IL12) and present higher glycolysis and oxygen consumption when compared with M-CSFmacs. L929macs also have increased mitochondrial mass, with higher percentage of dysfunctional mitochondria. This sort of information can help direct further studies towards a more specific approach for macrophage generation.

2.
Nutrients ; 12(4)2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32218109

RESUMO

Diabetic nephropathy (DN) is a major microvascular complication of diabetes. Obesity and hyperlipidemia, fueled by unhealthy food habits, are risk factors to glomerular filtration rate (GFR) decline and DN progression. Several studies recommend that diabetic patients should be screened early (in prediabetes) for kidney disease, in order to prevent advanced stages, for whom the current interventions are clearly inefficient. This ambition greatly depends on the existence of accurate early biomarkers and novel molecular targets, which only may arise with a more thorough knowledge of disease pathophysiology. We used a rat model of prediabetes induced by 23 weeks of high-sugar/high-fat (HSuHF) diet to characterize the phenotype of early renal dysfunction and injury. When compared with the control animals, HSuHF-treated rats displayed a metabolic phenotype compatible with obese prediabetes, displaying impaired glucose tolerance and insulin sensitivity, along with hypertriglyceridemia, and lipid peroxidation. Despite unchanged creatinine levels, the prediabetic animals presented glomerular crescent-like lesions, accompanied by increased kidney Oil-Red-O staining, triglycerides content and mRNA expression of IL-6 and iNOS. This model of HSuHF-induced prediabetes can be a useful tool to study early features of DN, namely crescent-like lesions, an early signature that deserves in-depth elucidation.

3.
Med Phys ; 47(1): 52-63, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31299096

RESUMO

PURPOSE: Wireless Capsule Endoscopy (WCE) is a minimally invasive diagnosis tool for lesion detection in the gastrointestinal tract, reaching places where conventional endoscopy is unable to. However, the significant amount of acquired data leads to difficulties in the diagnosis by the physicians; which can be eased with computer assistance. This paper addresses a method for the automatic detection of tumors in WCE by using a two-step based procedure: region of interest selection and classification. METHODS: The first step aims to separate abnormal from normal tissue by using automatic segmentation based on a Gaussian Mixture Model (GMM). A modified version of the Anderson method for convergence acceleration of the expectation-maximization (EM) algorithm is proposed. The proposed features for both segmentation and classification are based on the CIELab color space, as a way of bypassing lightness variations, where the L component is discarded. Tissue variability among subjects, light inhomogeneities and even intensity differences among different devices can be overcome by using simultaneously features from both regions. In the second step, an ensemble system with partition of the training data with a new training scheme is proposed. At this stage, the gating network is trained after the experts have been trained decoupling the joint maximization of both modules. The partition module is also used at the test step, leading the incoming data to the most likely expert allowing incremental adaptation by preserving data diversity. RESULTS: This algorithm outperforms others based on texture features selected from Wavelets and Curvelets transforms, classified by a regular support vector machine (SVM) in more than 5%. CONCLUSIONS: This work shows that simpler features can outperform more elaborate ones if appropriately designed. In the current case, luminance was discarded to cope with saturated tissue, facilitating the color perception. Ensemble systems remain an open research field. In the current case, changes in both topology and training strategy have led to significant performance improvements. A system with this level of performance can be used in current clinical practice.

4.
J Craniofac Surg ; 31(1): 41-45, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31369510

RESUMO

BACKGROUND: The identification of variables potentially correlated with speech outcome, following posterior pharyngeal fat grafting for treatment of velopharyngeal insufficiency (VPI), can provide useful information to guide decision-making and preoperative counseling. This study assessed the predictors of speech outcome after posterior pharyngeal fat grafting for VPI management. METHODS: One hundred and sixty-seven consecutive patients with repaired cleft palate and VPI who underwent posterior pharyngeal fat grafting were retrospectively enrolled. Perceptual speech and nasendoscopic parameters were randomly rated by 3 blinded evaluators. Speech outcome was stratified based on previously published criteria. Bivariate and multivariate analyses were performed to identify independent predictors of 15-month postoperative speech outcomes. RESULTS: Large velopharyngeal gap, higher number of previous palatal surgical procedures, and referral pattern (ie, patients who underwent primary palatoplasty elsewhere) were independently negative (for all, P < 0.05) predictors of speech outcome, whereas small velopharyngeal gap size was positively (P < 0.05) correlated with this outcome. Age, sex, race, Veau hierarchy, syndromic diagnosis, Angle classification of malocclusion, type of primary palatoplasty, body mass index, obstructive sleep apnea-related scores, surgical period, donor site, grafted volume, recipient site-related complications, and preoperative status (velopharyngeal closure pattern, hypernasality, audible nasal emissions, and intraoral pressure) were not associated (for all, P > 0.05) with speech outcomes. CONCLUSION: Posterior pharyngeal fat grafting improves speech function in patients with VPI, whereas gap size, number of previous palatal surgeries, and referral pattern affect the speech outcome.

5.
Lasers Med Sci ; 35(1): 43-49, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31098938

RESUMO

Optically tunable gold nanoparticles have been widely used in research with near-infrared light as a means to enhance laser-induced thermal therapy since it capitalizes on nanoparticles' plasmonic heating properties. There have been several studies published on numerical models replicating this therapy in such conditions. However, there are several limitations on some of the models which can render the model unfaithful to therapy simulations. In this paper, two techniques of simulating laser-induced thermal therapy with a high-absorbing localized region of interest inside a phantom are compared. To validate these models, we conducted an experiment of an agar-agar phantom with an inclusion reproducing it with both models. The phantom was optically characterized by absorption and total attenuation. The first model is based on the macroperspective solution of the radiative transfer equation given by the diffusion equation, which is then coupled with the Pennes bioheat equation to obtain the temperature. The second is a Monte Carlo model that considers a stochastic solution of the same equation and is also considered as input to the Pennes bioheat transfer equation which is then computed. The Monte Carlo is in good agreement with the experimental data having an average percentage difference of 4.5% and a correlation factor of 0.98, while the diffusion method comparison with experimental data is 61% and 0.95 respectively. The optical characterization of the phantom and its inclusion were also validated indirectly since the Monte Carlo, which used those parameters, was also validated. While knowing the temperature in all points inside a body during photothermal therapy is important, one has to be mindful of the model which fits the conditions and properties. There are several reasons to justify the discrepancy of the diffusion method: low-scattering conditions, absorption, and reduced scattering are comparable. The error bars that are normally associated when characterizing an optical phantom can justify also a part of that uncertainty. For low-size tumors in depth, one may have to increase the light dosage in photothermal therapies to have a more effective treatment.

6.
Phys Rev Lett ; 123(22): 221602, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31868414

RESUMO

We bootstrap the S matrix of massless particles in unitary, relativistic two dimensional quantum field theories. We find that the low energy expansion of such S matrices is strongly constrained by the existence of a UV completion. In the context of flux tube (FT) physics, this allows us to constrain several terms in the S matrix low energy expansion or-equivalently-on Wilson coefficients of several irrelevant operators showing up in the FT effective action. These bounds have direct implications for other physical quantities; for instance, they allow us to further bound the ground state energy as well as the level splitting of degenerate energy levels of large FTs. We find that the S matrices living at the boundary of the allowed space exhibit an intricate pattern of resonances with one sharper resonance whose quantum numbers, mass, and width are precisely those of the world-sheet axion proposed by Athenodorou, Bringoltz, and Teper and Dubovsky, Flauger, and Gorbenko. The general method proposed here should be extendable to massless S matrices in higher dimensions and should lead to new quantitative bounds on irrelevant operators in theories of Goldstones and, also, in gauge and gravity theories.

8.
Free Radic Biol Med ; 145: 61-66, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31525456

RESUMO

Over the past years, systemic derived cues that regulate cellular metabolism have been implicated in the regulation of immune responses. Ghrelin is an orexigenic hormone produced by enteroendocrine cells in the gastric mucosa with known immunoregulatory roles. The mechanism behind the function of ghrelin in immune cells, such as macrophages, is still poorly understood. Here, we explored the hypothesis that ghrelin leads to alterations in macrophage metabolism thus modulating macrophage function. We demonstrated that ghrelin exerts an immunomodulatory effect over LPS-activated peritoneal macrophages, as evidenced by inhibition of TNF-α and IL-1ß secretion and increased IL-12 production. Concomitantly, ghrelin increased mitochondrial membrane potential and increased respiratory rate. In agreement, ghrelin prevented LPS-induced ultrastructural damage in the mitochondria. Ghrelin also blunted LPS-induced glycolysis. In LPS-activated macrophages, glucose deprivation did not affect ghrelin-induced IL-12 secretion, whereas the inhibition of pyruvate transport and mitochondria-derived ATP abolished ghrelin-induced IL-12 secretion, indicating a dependence on mitochondrial function. Ghrelin pre-treatment of metabolic activated macrophages inhibited the secretion of TNF-α and enhanced IL-12 levels. Moreover, ghrelin effects on IL-12, and not on TNF-α, are dependent on mitochondria elongation, since ghrelin did not enhance IL-12 secretion in metabolic activated mitofusin-2 deficient macrophages. Thus, ghrelin affects macrophage mitochondrial metabolism and the subsequent macrophage function.

9.
Case Rep Med ; 2019: 9581605, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396284

RESUMO

Waldenström macroglobulinemia (WM) is a type of non-Hodgkin lymphoma in which cancer cells produce large amounts of an abnormal protein that can cause hyperviscosity syndrome (HVS). A 43-year-old woman with WM, who developed seizures, had a head computed tomography scan that showed signs of cerebral venous thrombosis (CVT). Nevertheless, the value of immunoglobulin M was lower than 50 g/L, and evaluation of serum viscosity was not performed. Moreover, there was no history of bleeding, and the eye funduscopy was normal. These findings lead to think of causes of CVT other than HVS in a patient with WM.

10.
J Clin Invest ; 129: 3717-3731, 2019 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-31380811

RESUMO

Palmitic acid esters of hydroxy stearic acids (PAHSAs) are endogenous antidiabetic and antiinflammatory lipids. Here, we show that PAHSAs protect against type 1 diabetes (T1D) and promote ß cell survival and function. Daily oral PAHSA administration to nonobese diabetic (NOD) mice delayed the onset of T1D and markedly reduced the incidence of T1D, whether PAHSAs were started before or after insulitis was established. PAHSAs reduced T and B cell infiltration and CD4+ and CD8+ T cell activation, while increasing Treg activation in pancreata of NOD mice. PAHSAs promoted ß cell proliferation in both NOD mice and MIN6 cells and increased the number of ß cells in NOD mice. PAHSAs attenuated cytokine-induced apoptotic and necrotic ß cell death and increased ß cell viability. The mechanism appears to involve a reduction of ER stress and MAPK signaling, since PAHSAs lowered ER stress in NOD mice, suppressed thapsigargin-induced PARP cleavage in human islets, and attenuated ERK1/2 and JNK1/2 activation in MIN6 cells. This appeared to be mediated in part by glucagon-like peptide 1 receptor (GLP-1R) and not the G protein-coupled receptor GPR40. PAHSAs also prevented impairment of glucose-stimulated insulin secretion and improved glucose tolerance in NOD mice. Thus, PAHSAs delayed the onset of T1D and reduced its incidence by attenuating immune responses and exerting direct protective effects on ß cell survival and function.

11.
Ann Plast Surg ; 83(2): 172-179, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31295169

RESUMO

BACKGROUND: This study aimed to evaluate the outcomes of posterior pharyngeal fat grafting for the management of velopharyngeal insufficiency using a simplified therapeutic algorithm and a tailored surgical technique. METHODS: This was a prospective study of consecutive nonsyndromic patients with repaired cleft palate and velopharyngeal insufficiency who were stratified according to a simplified algorithm (minimally scarred palate, transverse orientation of levator veli palatini, and pinhole-to-small velopharyngeal gaps) and who underwent tailored posterior pharyngeal fat grafting. The patients were screened for obstructive sleep apnea before and after surgery. Three blinded evaluators randomly rated perceptual speech (hypernasality, audible nasal emission, and intraoral pressure) and nasoendoscopic (velopharyngeal active gap size) characteristics using audio and video recordings. Successful speech outcome was defined as normal or borderline sufficient velopharyngeal function at 15 months after surgery. RESULTS: All included patients (n = 96) presented with a preoperative and postoperative low risk of obstructive sleep apnea. At 15 months after surgery, hypernasality (0.26 ± 0.53), audible nasal emissions (0.29 ± 0.48), intraoral pressure (0.1 ± 0.31), and velopharyngeal closure size (1.86 ± 0.34) were significantly decreased (all, P < 0.05) compared with the corresponding preoperative measurements (hypernasality, 2.17 ± 0.75; audible nasal emissions, 1.89 ± 0.82; intraoral pressure, 0.85 ± 0.35; and velopharyngeal closure size, 0.2 ± 0.49). In total, 84 (87.5%) patients showed successful speech outcomes. CONCLUSIONS: Tailored posterior pharyngeal fat grafting is an effective and safe surgical strategy for the management of velopharyngeal insufficiency in a selected cohort of patients with repaired cleft palate.

12.
Phys Rev Lett ; 122(24): 241604, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31322411

RESUMO

We consider the S-matrix bootstrap of four-dimensional scattering amplitudes with O(3) symmetry and no bound states. We explore the allowed space of scattering lengths which parametrize the interaction strength at threshold of the various scattering channels. Next we consider an application of this formalism to pion physics. A signature of pions is that they are derivatively coupled leading to (chiral) zeros in their scattering amplitudes. In this work we explore the multidimensional space of chiral zeros positions, scattering length values, and resonance mass values. Interestingly, we encounter lakes, peninsulas, and kinks depending on which sections of this intricate multidimensional space we consider. We discuss the remarkable location where QCD seems to lie in these plots, based on various experimental and theoretical expectations.

13.
Redox Biol ; 26: 101255, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31247505

RESUMO

Nearly 130 years after the first insights into the existence of mitochondria, new rolesassociated with these organelles continue to emerge. As essential hubs that dictate cell fate, mitochondria integrate cell physiology, signaling pathways and metabolism. Thus, recent research has focused on understanding how these multifaceted functions can be used to improve inflammatory responses and prevent cellular dysfunction. Here, we describe the role of mitochondria on the development and function of immune cells, highlighting metabolic aspects and pointing out some metabolic- independent features of mitochondria that sustain cell function.


Assuntos
Imunidade Adaptativa , Sistema Imunitário/fisiologia , Imunidade Inata , Mitocôndrias/imunologia , Dinâmica Mitocondrial/imunologia , /imunologia , Animais , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Glicólise/imunologia , Humanos , Inflamassomos/imunologia , Inflamassomos/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Mitocôndrias/metabolismo , Neutrófilos/imunologia , Neutrófilos/metabolismo , Oxirredução , Fosforilação Oxidativa
14.
J Leukoc Biol ; 106(3): 703-716, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31087711

RESUMO

Obesity is a pandemic disease affecting around 15% of the global population. Obesity is a major risk factor for other conditions, such as type 2 diabetes and cardiovascular diseases. The adipose tissue is the main secretor of leptin, an adipokine responsible for the regulation of food intake and energy expenditure. Obese individuals become hyperleptinemic due to increased adipogenesis. Leptin acts through the leptin receptor and induces several immunometabolic changes in different cell types, including adipocytes and Mϕs. Adipose tissue resident Mϕs (ATMs) are the largest leukocyte population in the adipose tissue and these ATMs are in constant contact with the excessive leptin levels secreted in obese conditions. Leptin activates both the JAK2-STAT3 and the PI3K-AKT-mTOR pathways. The activation of these pathways leads to intracellular metabolic changes, with increased glucose uptake, upregulation of glycolytic enzymes, and disruption of mitochondrial function, as well as immunologic alterations, such as increased phagocytic activity and proinflammatory cytokines secretion. Here, we discuss the immunometabolic effects of leptin in Mϕs and how hyperleptinemia can contribute to the low-grade systemic inflammation in obesity.

15.
J Biol Chem ; 294(24): 9342-9357, 2019 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-31040181

RESUMO

Triple-negative breast cancers (TNBCs) lack progesterone and estrogen receptors and do not have amplified human epidermal growth factor receptor 2, the main therapeutic targets for managing breast cancer. TNBCs have an altered metabolism, including an increased Warburg effect and glutamine dependence, making the glutaminase inhibitor CB-839 therapeutically promising for this tumor type. Accordingly, CB-839 is currently in phase I/II clinical trials. However, not all TNBCs respond to CB-839 treatment, and the tumor resistance mechanism is not yet fully understood. Here we classified cell lines as CB-839-sensitive or -resistant according to their growth responses to CB-839. Compared with sensitive cells, resistant cells were less glutaminolytic and, upon CB-839 treatment, exhibited a smaller decrease in ATP content and less mitochondrial fragmentation, an indicator of poor mitochondrial health. Transcriptional analyses revealed that the expression levels of genes linked to lipid metabolism were altered between sensitive and resistant cells and between breast cancer tissues (available from The Cancer Genome Atlas project) with low versus high glutaminase (GLS) gene expression. Of note, CB-839-resistant TNBC cells had increased carnitine palmitoyltransferase 2 (CPT2) protein and CPT1 activity levels. In agreement, CB-839-resistant TNBC cells mobilized more fatty acids into mitochondria for oxidation, which responded to AMP-activated protein kinase and acetyl-CoA carboxylase signaling. Moreover, chemical inhibition of both glutaminase and CPT1 decreased cell proliferation and migration of CB-839-resistant cells compared with single inhibition of each enzyme. We propose that dual targeting of glutaminase and CPT1 activities may have therapeutic relevance for managing CB-839-resistant tumors.


Assuntos
Benzenoacetamidas/farmacologia , Carnitina O-Palmitoiltransferase/antagonistas & inibidores , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Glutaminase/antagonistas & inibidores , Glutamina/metabolismo , Tiadiazóis/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Feminino , Humanos , Oxirredução , Neoplasias de Mama Triplo Negativas/enzimologia , Neoplasias de Mama Triplo Negativas/patologia , Células Tumorais Cultivadas
16.
Eur J Surg Oncol ; 45(9): 1559-1566, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31006589

RESUMO

BACKGROUND: Rectal cancer surgery conveys significant morbidity/mortality, long-term functional impairment and urinary & sexual dysfunction, especially if associated with neoadjuvant chemoradiotherapy (ChRT). Watch & Wait (W&W) is gaining momentum as an option for patients with clinical complete response (cCR) after ChRT. Approximately 30% will develop a local regrowth (RG) and need deferred surgery. Our study aimed to assess the short-term clinical outcomes after surgery for regrowths. PATIENTS AND METHODS: Consecutive rectal cancer patients from a tertiary institution who underwent neoadjuvant ChRT, between January 2013 and October 2018, were identified from a prospectively maintained database. Patients with RG under W&W surveillance were operated - regrowth deferred surgery (RDS) group - and compared to those with persistent disease after ChRT who did undergo surgery - non-deferred surgery (NDS) group. RESULTS: Total of 124 patients received neoadjuvant treatment: 46 (37%) underwent surgery for persistent disease; 78 (63%) with cCR entered W&W. Twenty three developed RG and underwent surgery, while 55 remain under surveillance. RDS group had lower tumors than NDS group (2.3 cm ±â€¯2 vs 4.5 cm ±â€¯3, p = 0.002). All RG underwent minimally invasive surgery (MIS). Anastomotic leaks, 30-day morbidity, reintervention and readmission rates were similar. Pathology features and 3-year oncological outcomes were identical between groups. CONCLUSION: Patients with initial cCR and local regrowth may be safely managed by deferred surgery. Short-term outcomes suggest equivalent results to patients with incomplete clinical response and immediate radical surgery. Delayed MIS appears to have no negative impact on oncological outcomes.

17.
J Cell Physiol ; 234(10): 19048-19058, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30924162

RESUMO

Prostate development and function are regulated by androgens. Epithelial cell apoptosis in response to androgen deprivation is caspase-9-dependent and peaks at Day 3 after castration. However, isolated epithelial cells survive in the absence of androgens. Znf142 showed an on-off expression pattern in intraepithelial CD68-positive macrophages, with the on-phase at Day 3 after castration. Rats treated with gadolinium chloride to deplete macrophages showed a significant drop in apoptosis, suggesting a causal relationship between macrophages and epithelial cell apoptosis. Intraepithelial M1-polarization was also limited to Day 3, and the inducible nitric oxide synthase (iNOS) knockout mice showed significantly less apoptosis than wild-type controls. The epithelial cells showed focal DNA double-strand breaks (DSB), 8-oxoguanine, and protein tyrosine-nitrosylation, fingerprints of exposure to peroxinitrite. Cultured epithelial cells induced M1-polarization and showed focal DSB and underwent apoptosis. The same phenomena were reproduced in LNCaP cells cocultured with Raw 264.7 macrophages. In conclusion, the M1 142 -macrophage (named after Znf142) attack causes activation of the intrinsic apoptosis pathway in epithelial cells after castration.

18.
Ann Biomed Eng ; 47(6): 1446-1462, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30919139

RESUMO

Angioectasias are lesions that occur in the blood vessels of the bowel and are the cause of more than 8% of all gastrointestinal bleeding episodes. They are usually classified as bleeding related lesions, however current state-of-the-art bleeding detection algorithms present low sensitivity in the detection of these lesions. This paper proposes a methodology for the automatic detection of angioectasias in wireless capsule endoscopy (WCE) videos. This method relies on the automatic selection of a region of interest, selected by using an image segmentation module based on the Maximum a Posteriori (MAP) approach where a new accelerated version of the Expectation-Maximization (EM) algorithm is also proposed. Spatial context information is modeled in the prior probability density function by using Markov Random Fields with the inclusion of a weighted boundary function. Higher order statistics computed in the CIELab color space with the luminance component removed and intensity normalization of high reflectance regions, showed to be effective features regarding angioectasia detection. The proposed method outperforms some current state of the art algorithms, achieving sensitivity and specificity values of more than 96% in a database containing 800 WCE frames labeled by two gastroenterologists.


Assuntos
Endoscopia por Cápsula , Hemorragia Gastrointestinal/diagnóstico , Intestino Delgado , Algoritmos , Humanos , Interpretação de Imagem Assistida por Computador
19.
Proc Natl Acad Sci U S A ; 116(12): 5747-5755, 2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30833389

RESUMO

Spike timing is thought to play a critical role in neural computation and communication. Methods for adjusting spike timing are therefore of great interest to researchers and clinicians alike. Transcranial electrical stimulation (tES) is a noninvasive technique that uses weak electric fields to manipulate brain activity. Early results have suggested that this technique can improve subjects' behavioral performance on a wide range of tasks and ameliorate some clinical conditions. Nevertheless, considerable skepticism remains about its efficacy, especially because the electric fields reaching the brain during tES are small, whereas the likelihood of indirect effects is large. Our understanding of its effects in humans is largely based on extrapolations from simple model systems and indirect measures of neural activity. As a result, fundamental questions remain about whether and how tES can influence neuronal activity in the human brain. Here, we demonstrate that tES, as typically applied to humans, affects the firing patterns of individual neurons in alert nonhuman primates, which are the best available animal model for the human brain. Specifically, tES consistently influences the timing, but not the rate, of spiking activity within the targeted brain region. Such effects are frequency- and location-specific and can reach deep brain structures; control experiments show that they cannot be explained by sensory stimulation or other indirect influences. These data thus provide a strong mechanistic rationale for the use of tES in humans and will help guide the development of future tES applications.


Assuntos
Potenciais de Ação/fisiologia , Neurônios/fisiologia , Estimulação Transcraniana por Corrente Contínua/métodos , Animais , Encéfalo/fisiologia , Estimulação Elétrica/métodos , Eletroencefalografia , Macaca mulatta/fisiologia , Masculino , Primatas
20.
Mol Ecol ; 28(7): 1784-1800, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30768810

RESUMO

Diversification and speciation of terrestrial organisms are anticipated in oceanic islands such as Macaronesia, a group of Atlantic islands that have remained unconnected to continental landmasses. Hitherto, the diversification of marine organisms in oceanic islands, especially those with low vagility, has received little direct empirical analysis using molecular markers. Here, we focus on such a case study, through applying a multilocus molecular approach to investigate the diversity and evolution of a group that lacks a planktonic larval stage, the isopod genus Dynamene, in Macaronesia and Northeast Atlantic. Sequences of two mitochondrial (cytochrome c oxidase subunit I and 16S rRNA) and two nuclear (18S rRNA and 28S rRNA) loci were obtained from specimens of Dynamene edwardsi (Lucas, 1849), Dynamene magnitorata Holdich, 1968 and Dynamene bidentata (Adams, 1800) collected along the Northeast Atlantic and Macaronesia. Although no major phylogeographic structure was detected in D. bidentata and D. magnitorata, from five to nine deeply divergent lineages were evident within D. edwardsi. The divergent lineages displayed genetic distances comparable to those found among established species of peracarids. D. edwardsi exhibits a long, rich and complex phylogeographic history in Macaronesia, where the geodynamics of the islands possibly associated with founder effects and subsequent lack of gene flow among populations confounds patterns based on geographic proximity of targeted populations. Our findings collectively suggest a much larger role of oceanic islands in the diversification of marine invertebrates than previously anticipated. The work provides insights into the origins and dynamics of ongoing geographic segregation and associated deep divergence among sister evolutionary lineages in Macaronesia.


Assuntos
Especiação Genética , Genética Populacional , Isópodes/classificação , Animais , Organismos Aquáticos/genética , Oceano Atlântico , Efeito Fundador , Fluxo Gênico , Ilhas , Isópodes/genética , Filogeografia , RNA Ribossômico 16S/genética , RNA Ribossômico 18S/genética , RNA Ribossômico 28S/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA