RESUMO
The pulvinar is a heterogeneous thalamic nucleus, which is well developed in primates. One of its subdivisions, the medial pulvinar, is connected to many cortical areas, including the visual, auditory, and somatosensory cortices, as well as with multisensory areas and premotor areas. However, except for the visual modality, little is known about its sensory functions. A hypothesis is that, as a region of convergence of information from different sensory modalities, the medial pulvinar plays a role in multisensory integration. To test this hypothesis, 2 macaque monkeys were trained to a fixation task and the responses of single-units to visual, auditory, and auditory-visual stimuli were examined. Analysis revealed auditory, visual, and multisensory neurons in the medial pulvinar. It also revealed multisensory integration in this structure, mainly suppressive (the audiovisual response is less than the strongest unisensory response) and subadditive (the audiovisual response is less than the sum of the auditory and the visual responses). These findings suggest that the medial pulvinar is involved in multisensory integration.
Assuntos
Pulvinar , Animais , Macaca , Haplorrinos , Neurônios/fisiologia , Sensação , Percepção Auditiva/fisiologia , Estimulação Acústica , Estimulação Luminosa , Percepção Visual/fisiologiaRESUMO
Extracellular adenosine plays prominent roles in the brain in both physiological and pathological conditions. Adenosine can be generated following the degradation of extracellular nucleotides by various types of ectonucleotidases. Several ectonucleotidases are present in the brain parenchyma: ecto-nucleotide triphosphate diphosphohydrolases 1 and 3 (NTPDase 1 and 3), ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP 1), ecto-5'-nucleotidase (eN), and tissue non-specific alkaline phosphatase (TNAP, whose function in the brain has received little attention). Here we examined, in a living brain preparation, the role of these ectonucleotidases in generating extracellular adenosine. We recorded local field potentials evoked by electrical stimulation of the lateral olfactory tract in the mouse piriform cortex in vitro. Variations in adenosine level were evaluated by measuring changes in presynaptic inhibition generated by adenosine A1 receptors (A1Rs) activation. A1R-mediated presynaptic inhibition was present endogenously and was enhanced by bath-applied AMP and ATP. We hypothesized that inhibiting ectonucleotidases would reduce extracellular adenosine concentration, which would result in a weakening of presynaptic inhibition. However, inhibiting TNAP had no effect in controlling endogenous adenosine action and no effect on presynaptic inhibition induced by bath-applied AMP. Furthermore, contrary to our expectation, inhibiting TNAP reinforced, rather than reduced, presynaptic inhibition induced by bath-applied ATP. Similarly, inhibition of NTPDase 1 and 3, NPP1, and eN induced stronger, rather than weaker, presynaptic inhibition, both in endogenous condition and with bath-applied ATP and AMP. Consequently, attempts to suppress the functions of extracellular adenosine by blocking its extracellular synthesis in living brain tissue could have functional impacts opposite to those anticipated.
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Córtex Cerebral/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Nucleotidases/antagonistas & inibidores , Transmissão Sináptica/efeitos dos fármacos , 5'-Nucleotidase/antagonistas & inibidores , Adenosina/metabolismo , Agonistas do Receptor A1 de Adenosina/farmacologia , Monofosfato de Adenosina/farmacologia , Trifosfato de Adenosina/farmacologia , Fosfatase Alcalina/antagonistas & inibidores , Animais , Estimulação Elétrica , Potenciais Evocados/efeitos dos fármacos , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Bulbo Olfatório/efeitos dos fármacos , Receptor A1 de Adenosina/efeitos dos fármacos , Receptor A1 de Adenosina/metabolismoRESUMO
Basaloid follicular hamartomas (BFH) are benign small basaloid skin tumors that can present as solitary or multiple lesions. Congenital BFH lesions arranged in a segmental distribution have been described, suggesting they derive from a somatic post-zygotic mutational event. Previously, BFH were described in Happle-Tinschert syndrome, which results from a post-zygotic SMO variant and is characterized by segmental BFH with variable involvement of the teeth, skeleton, and central nervous system. Here, we describe two patients with isolated segmental BFH and no systemic involvement. Paired whole exome sequencing of BFH and normal tissue revealed a pathogenic SMO c.1234 C>T, p.L412F variant restricted to BFH tissue. We characterized the proliferation index and expression of Hedgehog and Wnt/beta-catenin pathway related proteins in segmental BFH compared to sporadic basal cell carcinomas (BCCs) and found that segmental BFH had a lower proliferation index. Although segmental BFH expressed a similar level of Gli-1 compared to BCCs, levels of LEF-1 and SOX-9 expression in BFH were weaker for both and patchier for LEF-1. Our results show that a somatic SMO activating variant causes segmental BFH. Since these patients are prone to developing BCCs, differences in SOX9, LEF1, and Ki-67 expression can help distinguish between these two basaloid lesions.
Assuntos
Carcinoma Basocelular , Hamartoma , Dermatopatias , Neoplasias Cutâneas , Humanos , Folículo Piloso/anormalidades , Folículo Piloso/metabolismo , Folículo Piloso/patologia , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/genética , Carcinoma Basocelular/metabolismo , Hamartoma/diagnóstico , Hamartoma/genética , Hamartoma/metabolismo , Dermatopatias/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Receptor Smoothened/genéticaRESUMO
BACKGROUND: Patients of color are disproportionately impacted by vitiligo. Access to treatment depends greatly on insurance coverage. We, therefore, assessed current vitiligo treatment coverage policies across major United States health insurers to determine current patterns and coverage gaps for vitiligo. METHODS: The study surveyed 15 commercial health care insurers, 50 BlueCross BlueShield (BCBS) plans, Medicare, Medicaid, and Veterans Affairs. Information on treatment coverage for vitiligo, specifically pimecrolimus and tacrolimus, excimer laser therapy, PUVA, and narrow-band (nb)UVB, was collected via an online review of insurance policy documents, confirmed with phone calls to organization representatives, or via a survey of Medicaid providers, and state Medicaid directors. RESULTS: Of 17 organizations with regional or national coverage policies, 12% did not cover topical calcineurin inhibitors, 56% did not cover nbUVB phototherapy, 53% did not cover PUVA phototherapy, and 41% did not cover laser therapy. For BCBS, pimecrolimus and tacrolimus were not covered in 39% and 35% of states, respectively. NbUVB and PUVA therapy were not covered in 20% and 10% of states, respectively. Excimer laser therapy was not covered in 82% of states. Out of 32 states with accessible Medicaid information, 11 did not cover topicals, 5 did not cover nbUVB, 4 did not cover PUVA, and 7 did not cover laser. Two commonly cited reasons for coverage denial were that the treatment indication was considered cosmetic, and certain therapies are not FDA-approved. CONCLUSIONS: There is inequity in the distribution of health among vitiligo patients given current patterns of insurance coverage for treatment, which may have disproportionate impact on patients of color.
Assuntos
Vitiligo , Idoso , Criança , Atenção à Saúde , Humanos , Cobertura do Seguro , Medicare , Terapia PUVA , Estados Unidos , Vitiligo/terapiaRESUMO
Tissue non-specific alkaline phosphatase (TNAP) is a key player of bone mineralization and TNAP gene (ALPL) mutations in human are responsible for hypophosphatasia (HPP), a rare heritable disease affecting the mineralization of bones and teeth. Moreover, TNAP is also expressed by brain cells and the severe forms of HPP are associated with neurological disorders, including epilepsy and brain morphological anomalies. However, TNAP's role in the nervous system remains poorly understood. To investigate its neuronal functions, we aimed to identify without any a priori the metabolites regulated by TNAP in the nervous tissue. For this purpose we used 1 H- and 31 P NMR to analyze the brain metabolome of Alpl (Akp2) mice null for TNAP function, a well-described model of infantile HPP. Among 39 metabolites identified in brain extracts of 1-week-old animals, eight displayed significantly different concentration in Akp2-/- compared to Akp2+/+ and Akp2+/- mice: cystathionine, adenosine, GABA, methionine, histidine, 3-methylhistidine, N-acetylaspartate (NAA), and N-acetyl-aspartyl-glutamate, with cystathionine and adenosine levels displaying the strongest alteration. These metabolites identify several biochemical processes that directly or indirectly involve TNAP function, in particular through the regulation of ecto-nucleotide levels and of pyridoxal phosphate-dependent enzymes. Some of these metabolites are involved in neurotransmission (GABA, adenosine), in myelin synthesis (NAA, NAAG), and in the methionine cycle and transsulfuration pathway (cystathionine, methionine). Their disturbances may contribute to the neurodevelopmental and neurological phenotype of HPP.
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Fosfatase Alcalina/metabolismo , Encéfalo/metabolismo , Modelos Animais de Doenças , Hipofosfatasia/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Metabolômica/métodos , Fosfatase Alcalina/deficiência , Animais , Feminino , Hipofosfatasia/genética , Masculino , Camundongos , Camundongos KnockoutRESUMO
Tissue non-specific alkaline phosphatase (TNAP) may be involved in the synthesis of GABA and adenosine, which are the main inhibitory neurotransmitters in cortex. We explored this putative TNAP function through electrophysiological recording (local field potential ) in slices of mouse somatosensory cortex maintained in vitro. We used tetramisole, a well documented TNAP inhibitor, to block TNAP activity. We expected that inhibiting TNAP with tetramisole would lead to an increase of neuronal response amplitude, owing to a diminished availability of GABA and/or adenosine. Instead, we found that tetramisole reduced neuronal response amplitude in a dose-dependent manner. Tetramisole also decreased axonal conduction velocity. Levamisole had identical effects. Several control experiments demonstrated that these actions of tetramisole were independent from this compound acting on TNAP. In particular, tetramisole effects were not stereo-specific and they were not mimicked by another inhibitor of TNAP, MLS-0038949. The decrease of axonal conduction velocity and preliminary intracellular data suggest that tetramisole blocks voltage-dependent sodium channels. Our results imply that levamisole or tetramisole should not be used with the sole purpose of inhibiting TNAP in living excitable cells as it will also block all processes that are activity-dependent. Our data and a review of the literature indicate that tetramisole may have at least four different targets in the nervous system. We discuss these results with respect to the neurological side effects that were observed when levamisole and tetramisole were used for medical purposes, and that may recur nowadays due to the recent use of levamisole and tetramisole as cocaine adulterants.
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Fosfatase Alcalina/antagonistas & inibidores , Córtex Cerebral/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Levamisol/farmacologia , Neurônios/efeitos dos fármacos , Tetramizol/farmacologia , Fosfatase Alcalina/metabolismo , Animais , Córtex Cerebral/metabolismo , Relação Dose-Resposta a Droga , Feminino , Camundongos , Neurônios/fisiologia , Transmissão Sináptica/efeitos dos fármacosRESUMO
Alterations in lipid oxidation during exercise have been well studied, but limited data exists on the effects of passive heat exposure and exercise in the heat on changes in lipid oxidation. This study was designed to examine: (1) the effects of heat exposure on lipid metabolism during passive heating and subsequent exercise in the heat by focusing on changes in whole-body lipid oxidation and plasma lipid concentrations, and (2) the effects of extended passive pre-heating on exercise performance in the heat. Male participants (n=8) were passively heated for 120 min at 42 °C, then exercised on a treadmill in the same temperature at 50% VÌO2 max for 30 min (HEAT). This same procedure was followed on a separate occasion at 23 °C (CON). Results showed that lipid oxidation rates were not different between HEAT and CON during passive heating or exercise. However, non-esterified fatty acid (NEFA) concentrations were significantly higher following passive heating (618 µM, 95% CI: 479-757) compared to CON (391 µM, 95% CI: 270-511). The same trend was observed following exercise (2036 µM, 95% CI: 1604-2469 for HEAT and 1351 µM, 95% CI: 1002-1699). Triacylglycerol, phospholipid and cholesterol levels were not different between HEAT and CON at any point. Four of 8 participants could not complete 30 min of exercise in HEAT, resulting in a 14% decline in total external work. Rate of perceived exertion over the final 5 min of exercise was higher in HEAT (9.5) than CON (5). We conclude that: (1) heat exposure results in increased circulating NEFA at rest and during exercise without changes in whole-body lipid utilization, and (2) passive pre-heating reduces work capacity during exercise in the heat and increases the perceived intensity of a given workload.
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Temperatura Corporal , Exercício Físico , Ácidos Graxos/metabolismo , Temperatura Alta , Metabolismo dos Lipídeos , Adulto , Peso Corporal , Dióxido de Carbono/metabolismo , Teste de Esforço , Frequência Cardíaca , Humanos , Lipídeos/sangue , Masculino , Consumo de Oxigênio , Ventilação Pulmonar , Temperatura Cutânea , Estresse Fisiológico , Termogênese , Adulto JovemRESUMO
This study explored predictions made from Lucille Iremonger's Phaeton theory (1970), which argues that individuals who show exceptional personal achievement in certain fields frequently have experienced childhoods that were marked by parental loss through death and desertion. Three groups were examined: eminent American writers, presidents of the USA, and the 100 Americans who were judged by Life magazine to have been the most influential in 20th century society. Bereavement was common in the childhoods of these outstanding individuals, but was also high, or even higher, for those individuals who achieved somewhat less eminence (less successful writers, and presidential also-rans). More than half the total set of the presidents and also-rans were orphans. Eminent Americans showed substantial although lower levels of parental loss, and nearly three-quarters had experienced difficult childhoods that were marked by some form of loss. Eminent Americans, like the presidents, tended to be first-borns; they also showed elevated levels of divorce, suicide, and name changing. The results provide support for the Phaeton theory, but suggest that the child's struggle to overcome other losses than bereavement may also promote eminence, as may the presence of significant mentors.
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Logro , Pessoas Famosas , Morte Parental/psicologia , Humanos , Estados UnidosRESUMO
Previous research has suggested that motivational processes outside an individual's conscious awareness may be primed so as to enhance or impair cognitive performance. The present study involved a conceptual replication of the 2010 study of Ciani and Sheldon (Experiments 1 and 2), employing the same materials and task, to test whether exposure to the letter A before an analogies test improved performance and the letter F impaired it, relative to the neutral letter J. It also examined the effect of pre-exposing participants before testing to a positive or negative verbal passage concerning letter grades. Priming was not found to have any effect: the participants (N = 116), under both pre-exposure conditions, gave analogies scores which were virtually identical whether they had been primed with A, F, or J, thus contradicting the previous results. It is concluded that there is a pressing need for more replications of priming experiments as well as other studies.
Assuntos
Logro , Atenção , Conscientização , Motivação , Feminino , Humanos , MasculinoRESUMO
Reduced levels of endothelial progenitor cells (EPCs) have been associated with increased cardiovascular (CV) risk, but limited data are available on EPC levels in the human immunodeficiency virus (HIV)-infected population. EPCs (CD45(dim)/CD34(+)/kinase domain receptor(+)) from 36 HIV-uninfected and 30 antiretroviral therapy-naive HIV-infected men without known CV risk factors were enumerated using flow cytometry. The mean EPC levels (± standard error of the mean) were 1.4 ± 0.5 cells/µL in the HIV-infected group and 3.7 ± 2.2 cells/µL in the control group (P = .92). EPC levels were not associated with disease parameters, such as CD4 cell count or viral load. Reductions in EPC levels do not seem to explain the increased risk of CV disease among HIV-infected men.
Assuntos
Células Endoteliais/citologia , Infecções por HIV/sangue , Células-Tronco/citologia , Adulto , Antígenos CD34/análise , Aterosclerose/etiologia , Contagem de Linfócito CD4 , Células Endoteliais/imunologia , Citometria de Fluxo , Humanos , Antígenos Comuns de Leucócito/análise , Masculino , Fatores de Risco , Estatísticas não Paramétricas , Células-Tronco/imunologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/análise , Carga ViralRESUMO
The spatiotemporal features of the "static" receptive field (RF), as revealed with flashing bars or spots, determine other RF properties. We examined how some of these static RF features vary with contrast and contrast adaptation in area V1 of the anesthetized macaque monkey. RFs were mapped with light and dark flashing bars presented at three different contrasts, with the low and medium contrasts eliciting approximately 1/3 and 2/3 of the high-contrast response amplitude. The main results are as follows: 1) RF widths decreased when contrast decreased; however, the amount of decrease was less than that expected from an iceberg model and closer to the expectation of a contrast invariance of the RF width. 2) Area tuning experiments with drifting gratings showed an opposite effect of contrast: an increase in preferred stimulus diameter when contrast decreased. This implies that the effect of contrast on preferred stimulus size is not predictable from the static RF. 3) Contrast adaptation attenuated the effect of contrast on RF amplitude but did not significantly modify RF width. 4) RF subregion overlap was only marginally affected by changes in contrast and contrast adaptation; the classification of cells as simple and complex, when established from subregion overlap, appears to be robust with respect to changes in contrast and adaptation state. Previous studies have shown that the spatiotemporal features of the RF depend largely on the stimuli used to map the RF. This study shows that contrast is one elemental feature that contributes to the dynamics of the RF.
Assuntos
Adaptação Fisiológica , Sensibilidades de Contraste , Córtex Visual/fisiologia , Potenciais de Ação , Animais , Macaca fascicularis , Masculino , Modelos Neurológicos , Estimulação Luminosa , Vias Visuais/fisiologiaRESUMO
Flexible intracerebral probes for neural recording and electrical stimulation have been the focus of many research works to achieve better compliance with the surrounding tissue while minimizing rejection. Strategies have been explored to find the best way to insert flexible probes into the brain while maintaining their flexibility once positioned. Here, we present a novel and versatile scalable batch fabrication approach to deliver ultrathin and flexible probes consisting of a silk-parylene bilayer. The biodegradable silk layer, whose degradation time is programmable, provides a temporary and programmable stiffener to allow the insertion of ultrathin parylene-based flexible devices. Our innovative and robust batch fabrication technology allows complete freedom over probe design in terms of materials, size, shape, and thickness. We demonstrate successful ex vivo insertion of the probe with acute high-fidelity recordings of epileptic seizures in field potentials as well as single-unit action potentials in mouse brain slices. Our novel technological solution for implanting ultraflexible devices in the brain while minimizing rejection risks shows high potential for use in both brain research and clinical therapies.
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A valid 1 item screen ("In the past 12 months, have you ever had an issue with your gambling?") is potentially important in both a primary care setting and in research applications where an extended screen is not practical or affordable. Prior research by Thomas et al. (A one item screening tool for problem gambling for use in primary care settings, Unpublished Manuscript, Monash University, 2010) and Thomas et al. (MJA 189(3):135-136, 2008) found that the 1 item screen provided acceptable performance when compared to the 9-item Problem Gambling Severity Index (PGSI, Ferris and Wynne in The Canadian problem gambling Index: Final report, Canadian Centre on Substance Abuse, 2001). The current study sought to replicate these findings in a different geographic area. Data were collected from a telephone survey of 1,292 respondents in Queensland. Results from the phone survey showed a very high proportion of false negatives (79%), indicating that approximately 4/5 of positively identified problem gamblers from the PGSI refused to admit to having any "issues with (their) gambling" in the last 12 months. Further investigation using Rasch analysis (Andrich in Medical Care, 42(1):7-16, 2004) revealed that while the internal construct validity of the PGSI was good, the 1 item screen was ineffective as an indicator of those who are presently at risk for problem gambling. One possible explanation for the discrepancy with past results is that the present study employed the qualifier of "In the past 12 months" to match with the questions on the PGSI, whereas the prior research excluded this timeframe limit. Nevertheless, the current study casts doubt on the ability or willingness of people with severe gambling problems to self-diagnose their behavior as problematic.
Assuntos
Comportamento Aditivo/diagnóstico , Jogo de Azar/diagnóstico , Controle Interno-Externo , Autoimagem , Inquéritos e Questionários/normas , Comportamento Aditivo/epidemiologia , Jogo de Azar/epidemiologia , Humanos , Queensland/epidemiologia , Reprodutibilidade dos Testes , Fatores de Risco , Meio SocialRESUMO
An experiment tested whether thinking about oneself, particularly in negative terms, increases gambling intensity on Electronic Gaming Machines (EGMs). Forty male and 65 Female participants, aged 18-76 (M = 46.2, SD = 15.3), were recruited through newspaper advertisements to play a laptop simulated EGM in Hervey Bay, Queensland, Australia. Prior to play, subjects in the test conditions audio tape-recorded 2 min of self reflection on either: (1) "things you like about yourself," or (2) "things you don't like about yourself." Immediately after the recordings, the subjects played an EGM that was programmed (rigged) with five wins in the first 20 spins, and indefinite losses thereafter. Participants gambled more intensively in terms of Average Bet Size, Number of Trials Played, and Speed of Betting in the negative self reflection condition compared to the control condition. The experiment supports the proposition that EGM gambling behavior is motivated by escape from negative self reflection.
Assuntos
Comportamento Aditivo/psicologia , Jogo de Azar/psicologia , Controle Interno-Externo , Internet , Autoimagem , Adulto , Idoso , Atitude Frente a Saúde , Austrália , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Recompensa , Assunção de Riscos , Comportamento Social , Interface Usuário-Computador , Adulto JovemRESUMO
In this study, we report a flexible implantable 4-channel microelectrode probe coated with highly porous and robust nanocomposite of poly (3,4-ethylenedioxythiophene) (PEDOT) and carbon nanofiber (CNF) as a solid doping template for high-performance in vivo neuronal recording and stimulation. A simple yet well-controlled deposition strategy was developed via in situ electrochemical polymerization technique to create a porous network of PEDOT and CNFs on a flexible 4-channel gold microelectrode probe. Different morphological and electrochemical characterizations showed that they exhibit remarkable and superior electrochemical properties, yielding microelectrodes combining high surface area, low impedance (16.8 ± 2 MΩ µm2 at 1 kHz) and elevated charge injection capabilities (7.6 ± 1.3 mC/cm2) that exceed those of pure and composite PEDOT layers. In addition, the PEDOT-CNF composite electrode exhibited extended biphasic charge cycle endurance and excellent performance under accelerated lifetime testing, resulting in a negligible physical delamination and/or degradation for long periods of electrical stimulation. In vitro testing on mouse brain slices showed that they can record spontaneous oscillatory field potentials as well as single-unit action potentials and allow to safely deliver electrical stimulation for evoking field potentials. The combined superior electrical properties, durability and 3D microstructure topology of the PEDOT-CNF composite electrodes demonstrate outstanding potential for developing future neural surface interfacing applications.
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Due to the increasing demand resulting from the use of REE in many fields of human life, a weathering profile developed on granites in the semi-arid region of Biou area (North-Cameroon) has been characterized for rare-earth elements (REE) exploration. The mineralogical compositions of weathered materials were revealed by X-ray diffraction (XRD). X-ray Fluorescence (XRF) and Inductively Coupled Plasmas-Mass Spectrometry (ICP-MS) have been used to determine the geochemical composition of granites and the overlying weathered materials. The S-type and peraluminous granites are constituted by quartz, orthoclase, microcline, plagioclase, biotite, muscovite, pyroxene and opaque minerals. Accessory minerals are probably responsible for the interesting contents in REE + Y and some trace elements (e.g., Zr, Zn, Ba, Rb). The weathering profile show from the bottom to the top: (i) saprolitic horizons; (ii) lower loose clayey horizon; (iii) iron duricrust horizon; (iv) upper loose clayey horizon; (v) and organo-mineral horizon. Some weathered rock fragments remain in the loose clayey and organo-mineral horizons. The mineralogical composition of the weathering materials is dominated by illite, muscovite and feldspar. The low weathering degree of the materials is justified by the climatic and reducing conditions. The large ion lithophiles and ferromagnesian elements (Mg, Fe, V, Cu, Co, Cs Cr, Ni, Sc and Li) which are supposed to be mobile are so much accumulated in the weathering materials. REE show very low degree of fractionation in weathering profile due probably to the lack of good drainage. The whole weathering materials shows high REE + Y contents as its parent rock. Geochemical mass balance and enrichment factor reveal that REE, especially light REE, are so much enriched in the iron duricrust horizon (ion-adsorption REE deposit type). Some heavy REE are also enriched in the lower loose clayey horizon. This first survey has revealed that the weathering materials developed on granites in Biou area are favorable for further REE exploration.
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The aim of the present study was to characterize the spatial and temporal features of synaptic and discharge receptive fields (RFs), and to quantify their relationships, in cat area 17. For this purpose, neurons were recorded intracellularly while high-frequency flashing bars were used to generate RFs maps for synaptic and spiking responses. Comparison of the maps shows that some features of the discharge RFs depended strongly on those of the synaptic RFs, whereas others were less dependent. Spiking RF duration depended poorly and spiking RF amplitude depended moderately on those of the underlying synaptic RFs. At the other extreme, the optimal spatial frequency and phase of the discharge RFs in simple cells were almost entirely inherited from those of the synaptic RFs. Subfield width, in both simple and complex cells, was less for spiking responses compared with synaptic responses, but synaptic to discharge width ratio was relatively variable from cell to cell. When considering the whole RF of simple cells, additional variability in width ratio resulted from the presence of additional synaptic subfields that remained subthreshold. Due to these additional, subthreshold subfields, spatial frequency tuning predicted from synaptic RFs appears sharper than that predicted from spiking RFs. Excitatory subfield overlap in spiking RFs was well predicted by subfield overlap at the synaptic level. When examined in different regions of the RF, latencies appeared to be quite variable, but this variability showed negligible dependence on distance from the RF center. Nevertheless, spiking response latency faithfully reflected synaptic response latency.
Assuntos
Potenciais de Ação/fisiologia , Potenciais Evocados Visuais/fisiologia , Rede Nervosa/fisiologia , Transmissão Sináptica/fisiologia , Córtex Visual/fisiologia , Campos Visuais/fisiologia , Animais , Gatos , Estimulação Luminosa/métodosRESUMO
BACKGROUND: Bovine tuberculosis, caused by Mycobacterium bovis, afflicts approximately 50 million cattle worldwide and is detected by the tuberculin skin test (TST). While it has long been recognized that purified protein derivative (PPD) tuberculin is composed of a mixture of M. bovis derived protein components, little is known about the quality, relative quantity and identity of the proteins that make up PPD tuberculin. We manufactured a sterile filtered PPD tuberculin (SF-PPD) from a nine-week-old M. bovis culture supernatant in order to characterise the culture filtrate proteins (CFP) which make up M. bovis PPD tuberculin and to compare the antibody response of M. bovis infected versus M. bovis sensitized cattle. RESULTS: SF-PPD resolved into approximately 200 discrete spots using two-dimensional polyacrylamide gel electrophoresis (2-DE) while fewer than 65 spots could be discerned from 2-DE gels of tuberculin derived from autoclaved culture supernatant. Two dimensional Western blot analyses indicated that sera from M. bovis sensitized cattle recognized additional SF-PPD antigens as compared to M. bovis infected cattle at seven weeks post infection/sensitization. However, application of a comparative tuberculin skin test resulted in an antibody boosting response to the same set of M. bovis CFPs in both the M. bovis infected and M. bovis sensitized cattle. CONCLUSIONS: We concluded that it is the heat sterilization of the M. bovis CFPs that causes severe structural changes to the M. bovis proteins. This work suggests that M. bovis infected cattle and cattle artificially sensitized to M. bovis with an injection of heat killed cells exhibit similar antibody responses to M. bovis antigens.
Assuntos
Mycobacterium bovis/imunologia , Tuberculina/imunologia , Tuberculose Bovina/imunologia , Tuberculose Bovina/microbiologia , Animais , Proteínas de Bactérias/química , Western Blotting , Bovinos , Eletroforese em Gel de Poliacrilamida , Temperatura Alta , Espectrometria de Massas , Mycobacterium bovis/química , Tuberculina/química , Tuberculose Bovina/sangueRESUMO
The origin of Earth's water remains unknown. Enstatite chondrite (EC) meteorites have similar isotopic composition to terrestrial rocks and thus may be representative of the material that formed Earth. ECs are presumed to be devoid of water because they formed in the inner Solar System. Earth's water is therefore generally attributed to the late addition of a small fraction of hydrated materials, such as carbonaceous chondrite meteorites, which originated in the outer Solar System where water was more abundant. We show that EC meteorites contain sufficient hydrogen to have delivered to Earth at least three times the mass of water in its oceans. EC hydrogen and nitrogen isotopic compositions match those of Earth's mantle, so EC-like asteroids might have contributed these volatile elements to Earth's crust and mantle.
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BACKGROUND: Recordings with tetrodes have proven to be more effective in isolating single neuron spiking activity than with single microwires. However, tetrodes have never been used in humans. We report on the characteristics, safety, compatibility with clinical intracranial recordings in epileptic patients, and performance, of a new type of hybrid electrode equipped with tetrodes. NEW METHOD: 240 standard clinical macroelectrodes and 102 hybrid electrodes were implanted in 28 patients. Hybrids (diameter 800⯵m) are made of 6 or 9 macro-contacts and 2 or 3 tetrodes (diameter 70-80⯵m). RESULTS: No clinical complication or adverse event was associated with the hybrids. Impedance and noise of recordings were stable over time. The design enabled multiscale spatial analyses that revealed physiopathological events which were sometimes specific to one tetrode, but could not be recorded on the macro-contacts. After spike sorting, the single-unit yield was similar to other hybrid electrodes and was sometimes as high as >10 neurons per tetrode. COMPARISON WITH EXISTING METHOD(S): This new hybrid electrode has a smaller diameter than other available hybrid electrodes. It provides novel spatial information due to the configuration of the tetrodes. The single-unit yield appears promising. CONCLUSIONS: This new hybrid electrode is safe, easy to use, and works satisfactorily for conducting multi-scale seizure and physiological analyses.