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1.
J Neurosci ; 43(28): 5204-5220, 2023 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-37328291

RESUMO

Fast gamma oscillations, generated within the retina, and transmitted to the cortex via the lateral geniculate nucleus (LGN), are thought to carry information about stimulus size and continuity. This hypothesis relies mainly on studies conducted under anesthesia and the extent to which it holds under more naturalistic conditions remains unclear. Using multielectrode recordings of spiking activity in the retina and the LGN of both male and female cats, we show that visually driven gamma oscillations are absent for awake states and are highly dependent on halothane (or isoflurane). Under ketamine, responses were nonoscillatory, as in the awake condition. Response entrainment to the monitor refresh was commonly observed up to 120 Hz and was superseded by the gamma oscillatory responses induced by halothane. Given that retinal gamma oscillations are contingent on halothane anesthesia and absent in the awake cat, such oscillations should be considered artifactual, thus playing no functional role in vision.SIGNIFICANCE STATEMENT Gamma rhythms have been proposed to be a robust encoding mechanism critical for visual processing. In the retinogeniculate system of the cat, many studies have shown gamma oscillations associated with responses to static stimuli. Here, we extend these observations to dynamic stimuli. An unexpected finding was that retinal gamma responses strongly depend on halothane concentration levels and are absent in the awake cat. These results weaken the notion that gamma in the retina is relevant for vision. Notably, retinal gamma shares many of the properties of cortical gamma. In this respect, oscillations induced by halothane in the retina may serve as a valuable preparation, although artificial, for studying oscillatory dynamics.


Assuntos
Ritmo Gama , Halotano , Masculino , Feminino , Animais , Retina/fisiologia , Corpos Geniculados/fisiologia , Visão Ocular , Estimulação Luminosa/métodos
2.
J Cell Sci ; 134(16)2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34345895

RESUMO

Mutations in the PKD2 gene cause autosomal-dominant polycystic kidney disease but the physiological role of polycystin-2, the protein product of PKD2, remains elusive. Polycystin-2 belongs to the transient receptor potential (TRP) family of non-selective cation channels. To test the hypothesis that altered ion channel properties of polycystin-2 compromise its putative role in a control circuit controlling lumen formation of renal tubular structures, we generated a mouse model in which we exchanged the pore loop of polycystin-2 with that of the closely related cation channel polycystin-2L1 (encoded by PKD2L1), thereby creating the protein polycystin-2poreL1. Functional characterization of this mutant channel in Xenopus laevis oocytes demonstrated that its electrophysiological properties differed from those of polycystin-2 and instead resembled the properties of polycystin-2L1, in particular regarding its permeability for Ca2+ ions. Homology modeling of the ion translocation pathway of polycystin-2poreL1 argues for a wider pore in polycystin-2poreL1 than in polycystin-2. In Pkd2poreL1 knock-in mice in which the endogenous polycystin-2 protein was replaced by polycystin-2poreL1 the diameter of collecting ducts was increased and collecting duct cysts developed in a strain-dependent fashion.


Assuntos
Cistos , Rim Policístico Autossômico Dominante , Animais , Canais de Cálcio , Túbulos Renais/metabolismo , Camundongos , Rim Policístico Autossômico Dominante/genética , Receptores de Superfície Celular , Transdução de Sinais , Canais de Cátion TRPP/genética , Canais de Cátion TRPP/metabolismo
3.
Analyst ; 147(23): 5283-5292, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36269058

RESUMO

The rate-limiting step for diagnostics development is the discovery and validation of biomarker analytes. We describe a new analyte-agnostic and label-free approach based on colorimetric reactions involving type I polymerization photoinitiators. We demonstrate that a chemically diverse array of hydrogels embedded with cleaved type I photoinitiators could act as microreactors, undergoing colorimetric reactions with bound analytes. The colorimetric signatures produced were visually distinctive and readable with a flatbed document scanner. Signatures of a broad range of sample types were accurately differentiated by unsupervised clustering without knowledge of any analytes bound to the array. The principles described have the potential to enable scalable and cost-effective analysis of complex samples.


Assuntos
Colorimetria , Língua , Polimerização , Hidrogéis
4.
Exp Brain Res ; 240(12): 3327-3337, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36322165

RESUMO

Schizophrenia (SCZ) can be described as a functional dysconnectivity syndrome that affects brain connectivity and circuitry. However, little is known about how sensory stimulation modulates network parameters in schizophrenia, such as their small-worldness (SW) during visual processing. To address this question, we applied graph theory algorithms to multi-electrode EEG recordings obtained during visual stimulation with a checkerboard pattern-reversal stimulus. Twenty-six volunteers participated in the study, 13 diagnosed with schizophrenia (SCZ; mean age = 38.3 years; SD = 9.61 years) and 13 healthy controls (HC; mean age = 28.92 years; SD = 12.92 years). The visually evoked potential (VEP) showed a global amplitude decrease (p < 0.05) for SCZ patients as opposed to HC but no differences in latency (p > 0.05). As a signature of functional connectivity, graph measures were obtained from the Magnitude-Squared Coherence between signals from pairs of occipital electrodes, separately for the alpha (8-13 Hz) and low-gamma (36-55 Hz) bands. For the alpha band, there was a significant effect of the visual stimulus on all measures (p < 0.05) but no group interaction between SCZ and HZ (p > 0.05). For the low-gamma spectrum, both groups showed a decrease of Characteristic Path Length (L) during visual stimulation (p < 0.05), but, contrary to the HC group, only SCZ significantly lowered their small-world (SW) connectivity index during visual stimulation (SCZ p < 0.05; HC p > 0.05). This indicates dysconnectivity of the functional network in the low-gamma band of SCZ during stimulation, which might indirectly reflect an altered ability to react to new sensory input in patients. These results provide novel evidence about a possible electrophysiological signature of the global deficits revealed by the application of graph theory onto electroencephalography in schizophrenia.


Assuntos
Mapeamento Encefálico , Eletroencefalografia , Vias Neurais , Estimulação Luminosa , Esquizofrenia , Adulto , Humanos , Encéfalo/fisiopatologia , Mapeamento Encefálico/métodos , Esquizofrenia/complicações , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatologia , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Potenciais Evocados Visuais , Vias Neurais/fisiopatologia
5.
Development ; 144(14): 2606-2617, 2017 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-28619824

RESUMO

Germ cell development involves major reprogramming of the epigenome to prime the zygote for totipotency. Histone 3 lysine 4 (H3K4) methylations are universal epigenetic marks mediated in mammals by six H3K4 methyltransferases related to fly Trithorax, including two yeast Set1 orthologs: Setd1a and Setd1b. Whereas Setd1a plays no role in oogenesis, we report that Setd1b deficiency causes female sterility in mice. Oocyte-specific Gdf9-iCre conditional knockout (Setd1bGdf9 cKO) ovaries develop through all stages; however, follicular loss accumulated with age and unfertilized metaphase II (MII) oocytes exhibited irregularities of the zona pellucida and meiotic spindle. Most Setd1bGdf9 cKO zygotes remained in the pronuclear stage and displayed polyspermy in the perivitelline space. Expression profiling of Setd1bGdf9 cKO MII oocytes revealed (1) that Setd1b promotes the expression of the major oocyte transcription factors including Obox1, 2, 5, 7, Meis2 and Sall4; and (2) twice as many mRNAs were upregulated than downregulated, suggesting that Setd1b also promotes the expression of negative regulators of oocyte development with multiple Zfp-KRAB factors implicated. Together, these findings indicate that Setd1b serves as maternal effect gene through regulation of the oocyte gene expression program.


Assuntos
Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Oogênese/genética , Oogênese/fisiologia , Animais , Blastocisto/citologia , Blastocisto/metabolismo , Epigênese Genética , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Fator 9 de Diferenciação de Crescimento/deficiência , Fator 9 de Diferenciação de Crescimento/genética , Fator 9 de Diferenciação de Crescimento/metabolismo , Histona-Lisina N-Metiltransferase/deficiência , Masculino , Herança Materna , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Oócitos/citologia , Oócitos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Análise de Célula Única , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Zona Pelúcida/metabolismo , Zona Pelúcida/patologia , Zigoto/citologia , Zigoto/metabolismo
6.
Eur J Neurosci ; 47(4): 358-369, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29178660

RESUMO

Features from outside the classical receptive field (CRF) can modulate the stimulus-driven activity of single cells in the primary visual cortex. This modulation, mediated by horizontal and feedback networks, has been extensively described as a variation of firing rate and is considered the basis of processing features as, for example, motion contrast. However, surround influences have also been identified in pairwise spiking or local field coherence. Yet, evidence about co-existence and integration of different neural signatures remains elusive. To compare multiple signatures, we recorded spiking and LFP activity evoked by stimuli exhibiting a motion contrast in the CRFs surround in anesthetized cat primary visual cortex. We chose natural-like scenes over gratings to avoid predominance of simple visual features, which could be easily represented by a rate code. We analyzed firing rates and phase-locking to low-gamma frequency in single cells and neuronal assemblies. Motion contrast was reflected in all measures but in semi-independent populations. Whereas activation of assemblies accompanied single neuron rates, their phase relations were modulated differently. Interestingly, only assembly phase relations mirrored the direction of movement of the surround and were selectively affected by thermal deactivation of visual interhemispheric connections. We argue that motion contrast can be reflected in complementary and superimposed neuronal signatures that can represent different surround features in independent neuronal populations.


Assuntos
Potenciais de Ação/fisiologia , Movimento (Física) , Movimento/fisiologia , Córtex Visual/fisiologia , Animais , Modelos Neurológicos , Neurônios/fisiologia , Estimulação Luminosa/métodos , Campos Visuais/fisiologia
7.
Arch Toxicol ; 92(7): 2385-2399, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29855658

RESUMO

The genetically modified maize event MON810 expresses a Bacillus thuringiensis-derived gene, which encodes the insecticidal protein Cry1Ab to control some lepidopteran insect pests such as the European corn borer. It has been claimed that the immune system may be affected following the oral/intragastric administration of the MON810 maize in various different animal species. In the frame of the EU-funded project GRACE, two 90-day feeding trials, the so-called studies D and E, were performed to analyze the humoral and cellular immune responses of male and female Wistar Han RCC rats fed the MON810 maize. A MON810 maize variety of Monsanto was used in the study D and a MON810 maize variety of Pioneer Hi-Bred was used in the study E. The total as well as the maize protein- and Cry1Ab-serum-specific IgG, IgM, IgA and IgE levels, the proliferative activity of the lymphocytes, the phagocytic activity of the granulocytes and monocytes, the respiratory burst of the phagocytes, a phenotypic analysis of spleen, thymus and lymph node cells as well as the in vitro production of cytokines by spleen cells were analyzed. No specific Cry1Ab immune response was observed in MON810 rats, and anti-maize protein antibody responses were similar in MON810 and control rats. Single parameters were sporadically altered in rats fed the MON810 maize when compared to control rats, but these alterations are considered to be of no immunotoxicological significance.


Assuntos
Ração Animal/toxicidade , Alimentos Geneticamente Modificados/toxicidade , Imunidade Celular , Imunidade Humoral , Plantas Geneticamente Modificadas/toxicidade , Zea mays/genética , Ração Animal/normas , Animais , Toxinas de Bacillus thuringiensis , Proteínas de Bactérias/imunologia , Qualidade de Produtos para o Consumidor , Endotoxinas/imunologia , Hipersensibilidade Alimentar/imunologia , Alimentos Geneticamente Modificados/normas , Proteínas Hemolisinas/imunologia , Imunoglobulinas/sangue , Plantas Geneticamente Modificadas/imunologia , Ratos Wistar , Testes de Toxicidade Crônica
8.
Neuroimage ; 146: 971-982, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-27664825

RESUMO

Ongoing brain activity exhibits patterns resembling neural ensembles co-activated by stimulation or task performance. Such patterns have been attributed to the brain's functional architecture, e.g. selective long-range connections. Here, we directly investigate the contribution of selective connections between hemispheres to spontaneous and evoked maps in cat area 18 close to the 17/18 border. We recorded voltage-sensitive dye imaging maps and spiking activity while manipulating interhemispheric input by reversibly deactivating corresponding contralateral areas. During deactivation, spontaneous maps continued to be generated with similar frequency and quality as in the intact network but a baseline cardinal bias disappeared. Consistently, neurons preferring either horizontal (HN) or vertical (VN), as opposed to oblique contours, decreased their resting state activity. HN decreased their rates also when stimulated visually. We conclude that structured spontaneous maps are primarily generated by thalamo- and/or intracortical connectivity. However, selective long-range connections through the corpus callosum - in perpetuation of the long-range intracortical network - contribute to a cardinal bias, possibly, because they are stronger or more frequent between neurons preferring horizontal and/or cardinal contours. As those contours are easier perceived and appear more frequently in natural environment, long-range connections might provide visual cortex with a grid for probabilistic grouping operations in a larger visual scene.


Assuntos
Neurônios/fisiologia , Córtex Visual/fisiologia , Percepção Visual/fisiologia , Animais , Gatos , Potenciais Evocados Visuais , Feminino , Masculino , Vias Neurais/fisiologia , Estimulação Luminosa , Campos Visuais
9.
Development ; 141(5): 1022-35, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24550110

RESUMO

Histone 3 lysine 4 (H3K4) methylation is a universal epigenetic mark. In mammals, there are six H3K4 methyltransferases related to yeast Set1 and fly Trithorax, including two orthologs of Set1: Setd1a and Setd1b. Here we show that mouse Setd1a is required for gastrulation, whereas Setd1b-deficient embryos survive to E11.5 but are grossly retarded. Setd1a knockout embryos implant but do not proceed past the epiblast. Furthermore, Setd1a is not required until the inner cell mass has formed, at which stage it has replaced Mll2 as the major H3K4 methyltransferase. Setd1a is required for embryonic, epiblast and neural stem cell survival and neural stem cell reprogramming, whereas Setd1b is dispensable. Deletion of Setd1a in embryonic stem cells resulted in rapid losses of bulk H3K4 methylation, pluripotency gene expression and proliferation, with G1 pileup. Setd1b overexpression could not rescue the proliferation defects caused by loss of Setd1a in embryonic stem cells. The precise developmental requirement for Setd1a suggests that gastrulation is regulated by a switch between the major H3K4 methyltransferases.


Assuntos
Histona-Lisina N-Metiltransferase/metabolismo , Animais , Apoptose/genética , Apoptose/fisiologia , Astrócitos/citologia , Astrócitos/metabolismo , Ciclo Celular/genética , Ciclo Celular/fisiologia , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Proliferação de Células , Gastrulação/genética , Gastrulação/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/genética , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Camadas Germinativas/citologia , Camadas Germinativas/metabolismo , Histona-Lisina N-Metiltransferase/genética , Camundongos , Camundongos Knockout , Neurônios/citologia , Neurônios/metabolismo
10.
Transgenic Res ; 26(4): 529-539, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28493168

RESUMO

Potatoes are a promising system for industrial production of the biopolymer cyanophycin as a second compound in addition to starch. To assess the efficiency in the field, we analysed the stability of the system, specifically its sensitivity to environmental factors. Field and greenhouse trials with transgenic potatoes (two independent events) were carried out for three years. The influence of environmental factors was measured and target compounds in the transgenic plants (cyanophycin, amino acids) were analysed for differences to control plants. Furthermore, non-target parameters (starch content, number, weight and size of tubers) were analysed for equivalence with control plants. The huge amount of data received was handled using modern statistical approaches to model the correlation between influencing environmental factors (year of cultivation, nitrogen fertilization, origin of plants, greenhouse or field cultivation) and key components (starch, amino acids, cyanophycin) and agronomic characteristics. General linear models were used for modelling, and standard effect sizes were applied to compare conventional and genetically modified plants. Altogether, the field trials prove that significant cyanophycin production is possible without reduction of starch content. Non-target compound composition seems to be equivalent under varying environmental conditions. Additionally, a quick test to measure cyanophycin content gives similar results compared to the extensive enzymatic test. This work facilitates the commercial cultivation of cyanophycin potatoes.


Assuntos
Proteínas de Bactérias/biossíntese , Plantas Geneticamente Modificadas/genética , Solanum tuberosum/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Solanum tuberosum/metabolismo , Amido/metabolismo
11.
BMC Cardiovasc Disord ; 17(1): 135, 2017 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-28545407

RESUMO

BACKGROUND: Effective treatment of paroxysmal atrial fibrillation (AF) is essential for reducing the risk of stroke and heart failure. Cryoballoon (CB) ablation has been developed as an alternative to the use of radiofrequency (RF) energy for electrical isolation of the pulmonary veins. Herein, we provide long-term data regarding the efficacy of CB ablation in comparison to RF. METHODS: FreezeAF was a randomised non-inferiority study comparing CB ablation with RF ablation for the treatment of patients with drug-refractory paroxysmal AF. Procedural success for the long-term follow-up (30 months) was defined as freedom from AF with an absence of persistent complications. RESULTS: Of the 315 patients that were randomised and received catheter ablation, 292 (92.7%) completed the 30-month follow-up (147 in the RF group and 145 in the CB group). The baseline characteristics of the RF and CB groups were similar. Single-procedure success was achieved by 40% of patients in the RF group and 42% of the CB group (p < 0.001 for non-inferiority). When including re-do procedures in the analysis, the multiple procedure success rate was 72% in the RF group and 76% in the CB group. CONCLUSION: The data provide long-term evidence that CB ablation is non-inferior to RF ablation, with high proportions of patients reporting freedom from AF 30 months after the index procedure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00774566 ; first registered October 16, 2008; first patient included October 20, 2008.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Criocirurgia , Veias Pulmonares/cirurgia , Irrigação Terapêutica , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Ablação por Cateter/efeitos adversos , Criocirurgia/efeitos adversos , Criocirurgia/instrumentação , Intervalo Livre de Doença , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Veias Pulmonares/fisiopatologia , Recidiva , Irrigação Terapêutica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
12.
Arch Toxicol ; 91(4): 1977-2006, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27730258

RESUMO

The data of four 90-day feeding trials and a 1-year feeding trial with the genetically modified (GM) maize MON810 in Wistar Han RCC rats performed in the frame of EU-funded project GRACE were analysed. Firstly, the data obtained from the groups having been fed the non-GM maize diets were combined to establish a historical control data set for Wistar Han RCC rats at the animal housing facility (Slovak Medical University, Bratislava, Slovakia). The variability of all parameters is described, and the reference values and ranges have been derived. Secondly, the consistency of statistically significant differences found in the five studies was analysed. In order to do so, the body weight development, organ weight, haematology and clinical biochemistry data were compared between the studies. Based on the historical control data, equivalence ranges for these parameters were defined, and the values measured in the GM maize-fed groups were compared with these equivalence ranges. Thirdly, the (statistical) power of these feeding studies with whole food/feed was assessed and detectable toxicologically relevant group differences were derived. Linear mixed models (LMM) were applied, and standardized effect sizes (SES) were calculated in order to compare different parameters as well as to provide an overall picture of group and study differences at a glance. The comparison of the five feeding trials showed a clear study effect in the control data. It also showed inconsistency both in the frequency of statistically significant differences and in the difference values between control and test groups.


Assuntos
Alimentos Geneticamente Modificados/toxicidade , Plantas Geneticamente Modificadas/toxicidade , Zea mays/genética , Ração Animal , Animais , Peso Corporal , Feminino , Modelos Lineares , Masculino , Tamanho do Órgão , Ratos , Ratos Wistar , Fatores de Tempo , Testes de Toxicidade/métodos
13.
Regul Toxicol Pharmacol ; 91 Suppl 1: S3-S13, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28958911

RESUMO

Prevailing knowledge gaps in linking specific molecular changes to apical outcomes and methodological uncertainties in the generation, storage, processing, and interpretation of 'omics data limit the application of 'omics technologies in regulatory toxicology. Against this background, the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) convened a workshop Applying 'omics technologies in chemicals risk assessment that is reported herein. Ahead of the workshop, multi-expert teams drafted frameworks on best practices for (i) a Good-Laboratory Practice-like context for collecting, storing and curating 'omics data; (ii) the processing of 'omics data; and (iii) weight-of-evidence approaches for integrating 'omics data. The workshop participants confirmed the relevance of these Frameworks to facilitate the regulatory applicability and use of 'omics data, and the workshop discussions provided input for their further elaboration. Additionally, the key objective (iv) to establish approaches to connect 'omics perturbations to phenotypic alterations was addressed. Generally, it was considered promising to strive to link gene expression changes and pathway perturbations to the phenotype by mapping them to specific adverse outcome pathways. While further work is necessary before gene expression changes can be used to establish safe levels of substance exposure, the ECETOC workshop provided important incentives towards achieving this goal.


Assuntos
Congressos como Assunto , Ecotoxicologia/métodos , Educação/métodos , Genômica/métodos , Metabolômica/métodos , Relatório de Pesquisa , Animais , Congressos como Assunto/tendências , Ecotoxicologia/tendências , Educação/tendências , Europa (Continente) , Genômica/tendências , Humanos , Metabolômica/tendências , Proteômica/métodos , Proteômica/tendências , Relatório de Pesquisa/tendências , Medição de Risco , Espanha
14.
J Neurosci ; 35(20): 7682-94, 2015 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-25995459

RESUMO

Neurons in the cerebral cortex are constantly integrating different types of inputs. Dependent on their origin, these inputs can be modulatory in many ways and, for example, change the neuron's responsiveness, sensitivity, or selectivity. To investigate the modulatory role of lateral input from the same level of cortical hierarchy, we recorded in the primary visual cortex of cats while controlling synaptic input from the corresponding contralateral hemisphere by reversible deactivation. Most neurons showed a pronounced decrease in their response to a visual stimulus of different contrasts and orientations. This indicates that the lateral network acts via an unspecific gain-setting mechanism, scaling the output of a neuron. However, the interhemispheric input also changed the contrast sensitivity of many neurons, thereby acting on the input. Such a contrast gain mechanism has important implications because it extends the role of the lateral network from pure response amplification to the modulation of a specific feature. Interestingly, for many neurons, we found a mixture of input and output gain modulation. Based on these findings and the known physiology of callosal connections in the visual system, we developed a simple model of lateral interhemispheric interactions. We conclude that the lateral network can act directly on its target, leading to a sensitivity change of a specific feature, while at the same time it also can act indirectly, leading to an unspecific gain setting. The relative contribution of these direct and indirect network effects determines the outcome for a particular neuron.


Assuntos
Lateralidade Funcional , Córtex Visual/fisiologia , Animais , Gatos , Sensibilidades de Contraste , Corpo Caloso/citologia , Corpo Caloso/fisiologia , Feminino , Masculino , Neurônios/fisiologia , Transmissão Sináptica , Córtex Visual/citologia
15.
Circulation ; 132(14): 1311-9, 2015 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-26283655

RESUMO

BACKGROUND: There is a lack of data on the comparative efficacy and procedural safety of open irrigated radiofrequency (RF) and cryoballoon catheter (CB) ablation for pulmonary vein isolation in patients with paroxysmal atrial fibrillation. METHODS AND RESULTS: In a prospective, noninferiority study, 315 patients were randomly assigned to RF (n=159) or CB (n=156) ablation. The primary end point was freedom from atrial arrhythmia with absence of persistent complications. Patients were largely comparable between groups with more vascular disease in the RF group (8.2% versus 2.6% for CB; P=0.028). The primary end point at 12 months was achieved by 70.7% with RF and 73.6% with CB (multiple procedure success), including 31 redo procedures in each group (19.5% of RF versus 19.9% of CB; P=0.933). For the intention-to-treat population, noninferiority of CB was revealed for the predefined inferiority margin (risk difference, 0.029; 95% confidence interval, -0.074 to 0.132; P<0.001). Rates at 6 months were 63.1% and 64.1% for the RF and CB groups (single procedure success), and noninferiority was confirmed (risk difference, 0.010; 95% confidence interval, -0.097 to 0.116; P=0.002). Periprocedural complications for the index procedure were more frequent in the CB group (5.0% RF, 12.2% CB; P=0.022) with a significant difference in phrenic nerve palsies (0% RF, 5.8% CB; P=0.002). CONCLUSION: This large, prospective, randomized, controlled study demonstrates noninferiority of CB ablation versus RF ablation for treating patients with paroxysmal atrial fibrillation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00774566.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Criocirurgia/métodos , Veias Pulmonares/cirurgia , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Doenças Cardiovasculares/epidemiologia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/instrumentação , Terapia Combinada , Comorbidade , Criocirurgia/efeitos adversos , Criocirurgia/instrumentação , Diabetes Mellitus/epidemiologia , Eletrocardiografia Ambulatorial , Feminino , Humanos , Imageamento Tridimensional , Complicações Intraoperatórias/epidemiologia , Complicações Intraoperatórias/etiologia , Masculino , Pessoa de Meia-Idade , Derrame Pericárdico/epidemiologia , Derrame Pericárdico/etiologia , Nervo Frênico/lesões , Hemorragia Pós-Operatória/induzido quimicamente , Estudos Prospectivos , Medição de Risco , Tamanho da Amostra , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Resultado do Tratamento
16.
Arch Toxicol ; 90(3): 731-51, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25724152

RESUMO

In this paper, we compare the traditional ANOVA approach to analysing data from 90-day toxicity studies with a more modern LMM approach, and we investigate the use of standardized effect sizes. The LMM approach is used to analyse weight or feed consumption data. When compared to the week-by-week ANOVA with multiple test results per week, this approach results in only one statement on differences in weight development between groups. Standardized effect sizes are calculated for the endpoints: weight, relative organ weights, haematology and clinical biochemistry. The endpoints are standardized, allowing different endpoints of the same study to be compared and providing an overall picture of group differences at a glance. Furthermore, in terms of standardized effect sizes, statistical significance and biological relevance are displayed simultaneously in a graph.


Assuntos
Modelos Lineares , Testes de Toxicidade/métodos , Testes de Toxicidade/normas , Toxicologia/estatística & dados numéricos , Análise de Variância , Animais , Peso Corporal , Masculino , Tamanho do Órgão , Plantas Geneticamente Modificadas , Ratos , Testes de Toxicidade/estatística & dados numéricos , Toxicologia/normas , Zea mays
17.
Arch Toxicol ; 90(10): 2531-62, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27439414

RESUMO

The GRACE (GMO Risk Assessment and Communication of Evidence; www.grace-fp7.eu ) project was funded by the European Commission within the 7th Framework Programme. A key objective of GRACE was to conduct 90-day animal feeding trials, animal studies with an extended time frame as well as analytical, in vitro and in silico studies on genetically modified (GM) maize in order to comparatively evaluate their use in GM plant risk assessment. In the present study, the results of a 1-year feeding trial with a GM maize MON810 variety, its near-isogenic non-GM comparator and an additional conventional maize variety are presented. The feeding trials were performed by taking into account the guidance for such studies published by the EFSA Scientific Committee in 2011 and the OECD Test Guideline 452. The results obtained show that the MON810 maize at a level of up to 33 % in the diet did not induce adverse effects in male and female Wistar Han RCC rats after a chronic exposure.


Assuntos
Ração Animal , Alimentos Geneticamente Modificados/toxicidade , Nível de Saúde , Plantas Geneticamente Modificadas/toxicidade , Zea mays/genética , Ração Animal/normas , Ração Animal/toxicidade , Animais , Feminino , Masculino , Ratos Endogâmicos , Medição de Risco , Testes de Toxicidade Crônica
18.
Regul Toxicol Pharmacol ; 82: 127-139, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27663666

RESUMO

The European Centre for the Ecotoxicology and Toxicology of Chemicals (ECETOC) organised a workshop to discuss the state-of-the-art research on noncoding RNAs (ncRNAs) as biomarkers in regulatory toxicology and as analytical and therapeutic agents. There was agreement that ncRNA expression profiling data requires careful evaluation to determine the utility of specific ncRNAs as biomarkers. To advance the use of ncRNA in regulatory toxicology, the following research priorities were identified: (1) Conduct comprehensive literature reviews to identify possibly suitable ncRNAs and areas of toxicology where ncRNA expression profiling could address prevailing scientific deficiencies. (2) Develop consensus on how to conduct ncRNA expression profiling in a toxicological context. (3) Conduct experimental projects, including, e.g., rat (90-day) oral toxicity studies, to evaluate the toxicological relevance of the expression profiles of selected ncRNAs. Thereby, physiological ncRNA expression profiles should be established, including the biological variability of healthy individuals. To substantiate the relevance of key ncRNAs for cell homeostasis or pathogenesis, molecular events should be dose-dependently linked with substance-induced apical effects. Applying a holistic approach, knowledge on ncRNAs, 'omics and epigenetics technologies should be integrated into adverse outcome pathways to improve the understanding of the functional roles of ncRNAs within a regulatory context.


Assuntos
RNA não Traduzido/genética , Testes de Toxicidade/métodos , Toxicologia/métodos , Animais , Relação Dose-Resposta a Droga , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Marcadores Genéticos , Genômica , Humanos , Modelos Animais , RNA não Traduzido/metabolismo , Reprodutibilidade dos Testes , Fatores de Tempo
19.
Proc Natl Acad Sci U S A ; 109(37): 14796-801, 2012 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-22927387

RESUMO

The occurrence of arthropods in amber exclusively from the Cretaceous and Cenozoic is widely regarded to be a result of the production and preservation of large amounts of tree resin beginning ca. 130 million years (Ma) ago. Abundant 230 million-year-old amber from the Late Triassic (Carnian) of northeastern Italy has previously yielded myriad microorganisms, but we report here that it also preserves arthropods some 100 Ma older than the earliest prior records in amber. The Triassic specimens are a nematoceran fly (Diptera) and two disparate species of mites, Triasacarus fedelei gen. et sp. nov., and Ampezzoa triassica gen. et sp. nov. These mites are the oldest definitive fossils of a group, the Eriophyoidea, which includes the gall mites and comprises at least 3,500 Recent species, 97% of which feed on angiosperms and represents one of the most specialized lineages of phytophagous arthropods. Antiquity of the gall mites in much their extant form was unexpected, particularly with the Triassic species already having many of their present-day features (such as only two pairs of legs); further, it establishes conifer feeding as an ancestral trait. Feeding by the fossil mites may have contributed to the formation of the amber droplets, but we find that the abundance of amber during the Carnian (ca. 230 Ma) is globally anomalous for the pre-Cretaceous and may, alternatively, be related to paleoclimate. Further recovery of arthropods in Carnian-aged amber is promising and will have profound implications for understanding the evolution of terrestrial members of the most diverse phylum of organisms.


Assuntos
Âmbar , Dípteros/anatomia & histologia , Dípteros/classificação , Fósseis , Ácaros/anatomia & histologia , Ácaros/classificação , Animais , Itália , Paleontologia
20.
J Neurosci ; 33(46): 18036-46, 2013 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-24227715

RESUMO

It is generally thought that callosal connections (CCs) in primary visual cortices serve to unify the visual scenery parted in two at the vertical midline (VM). Here, we present evidence that this applies also to visual features that do not cross yet but might cross the VM in the future. During reversible deactivation of the contralateral visual cortex in cats, we observed that ipsilaterally recorded neurons close to the border between areas 17 and 18 receive selective excitatory callosal input on both ongoing and evoked activity. In detail, neurons responding well to a vertical Gabor patch moving away from the deactivated hemifield decreased prestimulus and stimulus-driven activity much more than those preferring motion toward the cooled hemifield. Further, activity of neurons responding to horizontal lines decreased more than the response to vertical lines. Embedding a single Gabor into a collinear line context selectively stabilized responses, especially when the context was limited to the intact hemifield. These findings indicate that CCs interconnect not only neurons coding for similar orientations but also for similar directions of motion. We conclude that CCs anticipate stimulus features that are potentially relevant for both hemifields (i.e., coherent motion but also collinear shape) because already prestimulus activity and activity to stimuli not crossing the VM revealed feature specificity. Finally, we hypothesize that intrinsic and callosal networks processing different orientations and directions are anisotropic close to the VM facilitating perceptual grouping along likely future motion or (shape) trajectories before the visual stimulus arrives.


Assuntos
Antecipação Psicológica/fisiologia , Corpo Caloso/fisiologia , Percepção de Forma/fisiologia , Percepção de Movimento/fisiologia , Córtex Visual/fisiologia , Vias Visuais/fisiologia , Animais , Gatos , Masculino , Estimulação Luminosa/métodos
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