RESUMO
A hallmark of infection by the pathogen Helicobacter pylori, which colonizes the human gastric epithelium, is the simultaneous activation of the classical and alternative nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways, underlying inflammation and cell survival. Here, we report that the classical NF-κB target gene product A20 contributes to the negative regulation of alternative NF-κB signaling in gastric epithelial cells infected by H. pylori. Mechanistically, the de novo synthesized A20 protein interacts with tumor necrosis factor receptor-associated factor-interacting protein with forkhead-associated domain (TIFA) and thereby interferes with the association of TIFA with the NIK regulatory complex. We also show that alternative NF-κB activity contributes to the up-regulation of anti-apoptotic genes, such as baculoviral IAP repeat containing 2 (BIRC2), BIRC3 and B-cell lymphoma 2-related protein A1 (BCL2A1) in gastric epithelial cells. Furthermore, the observed over-expression of RelB in human gastric biopsies with type B gastritis and RelB-dependent suppression of apoptotic cell death emphasize an important role of the alternative NF-κB pathway in H. pylori infection.
Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Mucosa Gástrica/metabolismo , Infecções por Helicobacter/metabolismo , NF-kappa B/metabolismo , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo , Proteínas Reguladoras de Apoptose/genética , Proteína 3 com Repetições IAP de Baculovírus/genética , Proteína 3 com Repetições IAP de Baculovírus/metabolismo , Linhagem Celular Tumoral , Mucosa Gástrica/microbiologia , Gastrite/genética , Gastrite/metabolismo , Gastrite/microbiologia , Expressão Gênica , Técnicas de Inativação de Genes , Infecções por Helicobacter/genética , Infecções por Helicobacter/microbiologia , Helicobacter pylori/fisiologia , Interações Hospedeiro-Patógeno , Humanos , Antígenos de Histocompatibilidade Menor/genética , Antígenos de Histocompatibilidade Menor/metabolismo , NF-kappa B/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/genética , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Fator de Transcrição RelB/genética , Fator de Transcrição RelB/metabolismo , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genéticaRESUMO
PURPOSE: To examine visual evoked potential (VEP) changes following botulinum toxin type A (BTA) administration in patients with blepharospasm. METHODS: Patients diagnosed with blepharospasm receiving BTA administration were included in the study. Three groups, a control group and two study groups (patients examined 14 days after BTA administration-Study Group 1, and patients examined 28 days after BTA administration-Study Group 2) were evaluated. Dilated fundus examinations were performed following detailed ophthalmological examinations and VEP tests. Keypoint (Dantec, Denmark) and ISCEV criteria were adopted for pattern VEP (PVEP) recording. BTA was applied in the form of local injections at a total 15-30 units, at 2.5-5 units per injection. RESULTS: A mean 19.4 ± 3.2 units of BTA was used for each eye. N70 (ms), P100 (ms), and P100 (uV) values were statistically significantly lower in both study groups following drug administrations compared to the control group (p < 0.001 for all). Significant positive correlation was observed between increased P100 amplitudes and age in the control group (p = 0.008, r = 0.200). Significant negative correlation was observed between the BTA units used and decreased P100 amplitudes in both study groups 1 and 2 following drug administrations (p = 0.017, r = - 0.180 and p = 0.043, r = - 0.153, respectively). CONCLUSION: VEP may be an important method in the diagnosis and follow-up of blepharospasm and in determining the success of drug administration and additional therapeutic requirements.
Assuntos
Blefarospasmo , Toxinas Botulínicas Tipo A , Humanos , Blefarospasmo/tratamento farmacológico , Potenciais Evocados VisuaisRESUMO
PURPOSE: Coronary bypass surgery is emphasized in aetiology of ischemic optic neuropathy. Our aim in this study was to investigate the pattern visual evoked potentials (PVEP) in patients before and after coronary bypass surgery. METHODS: Thirty-one patients were included in the study. After a full ophthalmological evaluation, PVEP was assesed in the pre and postoperative periods. Operative times, hematological parameters, blood pressures, number of transfusions, body temperatures, anaesthetic drugs and systemic illnesses were recorded for each patient. RESULTS: The mean age of the patients were 59 ± 10.4 years. There was 22 men and 9 women in the study. Only 3 of them needed transfusion during the surgery. The mean duration of the surgery was 3.2 ± 0.7 h. None of the patients had a history of visual disturbance or postoperative ischemic optic neuropathy. The mean VEP P100 amplitude was not statistically significantly different but the mean VEP P100 latency showed statistically significant difference between the preoperative and postoperative periods. (p = 0.014) This significance was more appereant in patients with systemic illnesses. (p = 0.023) There was a positive correlation between the age and VEP P100 latency (r = 0.402, p < 0.05). CONCLUSIONS: Although surgical techniques and equipments are developing each day in the field of cardiopulmonary bypass surgery, the contributing factors such as hypothermia, anemia and diabetes still seem to affect neurophysiological functions even after a noncomplicated surgery.
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Potenciais Evocados Visuais , Neuropatia Óptica Isquêmica , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Neuropatia Óptica Isquêmica/etiologia , Transtornos da VisãoRESUMO
Studies examining children's face perception have revealed developmental changes in early and face-sensitive event-related potential (ERP) components. Children also tend to show racial biases in their face perception and evaluation of others. The current study examined how early face-sensitive ERPs are influenced by face race in children and adults. A second objective examined face recognition proficiency and implicit racial bias in relation to ERP responses to own- and other-race faces. Electroencephalographic responses were recorded while Caucasian children and adults viewed Caucasian and East Asian faces. Participants also completed recognition tasks and an IAT with Caucasian and East Asian faces. Other-race faces elicited larger P100 amplitudes than own-race faces. Furthermore, adults with better other-race recognition proficiency showed larger P100 amplitude responses to other-race faces compared with adults with worse other-race recognition proficiency. In addition, larger implicit biases favoring own-race individuals were associated with larger P100 to N170 peak-to-peak amplitudes for other-race faces in adults. In contrast, larger implicit biases favoring own-race individuals were associated with smaller P100 to N170 peak-to-peak amplitudes for both own- and other-race faces in 8- to 10-year-olds. There was also an age-related decrease in P100 to N170 peak-to-peak amplitudes for own-race faces among 5- to 10-year-olds with better own-race recognition proficiency. The age-related decrease in N170 latency for other-race faces was also more pronounced in 5- to 10-year-olds with better other-race recognition proficiency. Thus, recognition proficiency and implicit racial bias are associated with early ERP responses in adults and children, but in different ways.
Assuntos
Reconhecimento Facial , Grupos Raciais , Adulto , Criança , Eletroencefalografia , Potenciais Evocados , Humanos , Reconhecimento Visual de Modelos , Reconhecimento PsicológicoRESUMO
PURPOSE: To compare visual evoked potential (VEP) components in normal individuals and those with long-term methamphetamine and crystal methamphetamine use. METHODS: In this study, monocular pattern-reversal VEPs were recorded in 40 methamphetamine and crystal methamphetamine users and 38 normal individuals. Visual stimuli were high-contrast (99%) checkerboard patterns at 15 and 60 min of arc with a reversal rate of 1.53 reversals per second. RESULTS: A significant difference was seen between the two groups for the P100 peak time for the 60 min of arc checks (p = 0.002, d = 0.75, 4.61% higher peak time in the addicted group) and the 15 min of arc checks (p = 0.004, d = 0.73, 4.78% higher peak time in the addicted group). However, other VEP components were not significantly different between the two groups. CONCLUSIONS: The higher P100 peak time at both 15 and 60 min of arc in methamphetamine-dependent users reveals that VEPs are highly sensitive for the diagnosis of retinal and visual pathway lesions.
Assuntos
Potenciais Evocados Visuais , Metanfetamina , Humanos , Metanfetamina/efeitos adversos , Reconhecimento Visual de Modelos , Retina , Vias Visuais/fisiologiaRESUMO
Studies examining the visual perception of face race have revealed mixed findings regarding the presence or direction of effects on early face-sensitive event-related potential (ERP) components. Few studies have examined how early ERP components are influenced by individual differences in bottom-up and top-down processes involved in face perception, and how such factors might interact to influence early face-sensitive ERP components has yet to be investigated. Thus, the current study examined whether P100, N170, and P200 responses can be predicted by individual differences in own- and other-race face recognition, implicit racial bias, and their interaction. Race effects were observed in the P100, N170, and P200 responses. Other-race face recognition, implicit racial biases, and their interaction explained a significant amount of unique variability in N170 responses when viewing other-race faces. Responses to own-race faces were minimally influenced with only implicit racial bias predicting a significant amount of unique variability in N170 latency when viewing own-race faces. Face recognition, implicit racial bias, or their interaction did not predict P100 responses. The current findings suggest that face recognition abilities and its interaction with implicit racial bias modulate the early stages of other-race face processing.
Assuntos
Reconhecimento Facial , Racismo , Eletroencefalografia , Potenciais Evocados , Humanos , Reconhecimento Visual de Modelos , Grupos RaciaisRESUMO
BACKGROUND: The combined corticosteroid regimen of the original Optic Neuritis Treatment Trial (ONTT) is used in many centers to treat optic neuritis. Though pattern reversal visual evoked potentials (PRVEPs) are a sensitive, standard measure of visual conduction in optic neuritis, no studies hitherto have investigated the effect of combined ONTT regimen on PRVEPs. We aimed to determine the effect of combined corticosteroid regimen of the ONTT on changes of PRVEPs in patients with first-episode optic neuritis over 3 months post-treatment. METHODS: This is a prospective, observational study in which 44 patients with optic neuritis were seen pre-treatment (baseline) and follow-up, at 1 month (FU1) and 3 months (FU2). Twenty-nine patients were treated with ONTT combined regimen (ONTT+ Group) while 15 were conservatively managed without corticosteroids (ONTT- Group). The median latency and amplitude values of the P100 PRVEP component and the visual acuity (i.e. LogMAR values) at pre-treatment, FU1 and FU2 were compared in the two groups using Friedman's rank test and Wilcoxon Signed Ranks test. RESULTS: Median P100 latency improved significantly (to the normal range) as early as by 1 month after the commencement of treatment in the ONTT+ Group, and then remained significantly lower than the baseline over next 2 months. In the ONTT- Group, the median P100 latency improved more slowly over the two follow up assessments and reached the normal range by 3 months. Median visual acuity values also improved significantly at 1 and 3 months after the commencement of treatment in the ONTT+ Group but not in the ONTT- Group. CONCLUSION: ONTT combined corticosteroid regimen improves conduction in the visual pathways of patients with first-episode optic neuritis earlier than does conservative management. We provide electrodiagnostic evidence that combined ONTT regimen-compared with conservative management-results in early remission of visual conduction abnormalities in first-episode optic neuritis.
Assuntos
Potenciais Evocados Visuais , Neurite Óptica , Corticosteroides , Seguimentos , Humanos , Neurite Óptica/tratamento farmacológico , Estudos ProspectivosRESUMO
Background Idiopathic intracranial hypertension (IIH) is a clinical syndrome characterized by increased intracranial pressure in the absence of clinical, laboratory, or radiological findings of space-occupying lesion in the cranium. Papilledema is found in majority of the patients with IIH while it is absent in only about 5-6% of the patients. Methods Our primary objective was to evaluate the patients with IIH with (n: 45) and without (n: 15) papilledema using cranial MRI and VEP analyses and to compare the obtained results. Diagnosis of IIH according to ICHD-3 criteria admitted to and followed in our clinic before receiving any treatment between 2008 and 2018 were reviewed retrospectively after obtaining approval from the Ethics Committee. Results There was no statistically significant difference between both groups' ages (P: 0.494) while differences in lumbar puncture (LP) opening pressure and VAS were found to be statistically significant (p = 0.034, 0.001, respectively). In our VEP investigation, it was seen that latencies in the group without papilledema were seen to be closer to those in the control group (P latency: 0.706, P amplitude: 0.080). Increase in latency and decrease in amplitude were seen in the group with papilledema compared to the group without papilledema (p < 0.001). Conclusion In conclusion, alterations in the optic nerve may be detected with VEP investigation before the detection of papilledema through ophthalmoscopic examination in these patients. Thus, VEP investigation may be considered to have predictive value. VEP examination may be recommended in diagnosis and treatment and during follow-up periods.
Highlights Clinical imaging (cranial MRI-MR-angiography-venography) and VEP analyses were evaluated comparatively with detail in the patients with and without papilledema. In the literature, there are studies on VEP analysis. They have been done on acute and chronic stages of idiopathic intracranial hypertension. In the present study, the patients with and without papilledema were compared in contrast to other studies. Increased VEP latency was seen in both groups being especially more prominent in the group with papilledema.
Assuntos
Encéfalo/fisiopatologia , Papiledema/diagnóstico , Papiledema/fisiopatologia , Pseudotumor Cerebral/diagnóstico , Pseudotumor Cerebral/fisiopatologia , Adulto , Potenciais Evocados Visuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Papiledema/complicações , Pseudotumor Cerebral/complicações , Vias Visuais/fisiopatologia , Adulto JovemRESUMO
3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase (HMGL) is involved in branched-chain amino acid catabolism leading to acetyl-CoA production. Here, using bioinformatics analyses and protein sequence alignments, we found that in Arabidopsis thaliana a single gene encodes two HMGL isoforms differing in size (51 kDa, HMGL51 and 46 kDa, HMGL46). Similar to animal HMGLs, both isoforms comprised a C-terminal type 1 peroxisomal retention motif, and HMGL51 contained a mitochondrial leader peptide. We observed that only a shortened HMGL (35 kDa, HMGL35) is conserved across all kingdoms of life. Most notably, all plant HMGLs also contained a specific N-terminal extension (P100) that is located between the N-terminal mitochondrial targeting sequence TP35 and HMGL35 and is absent in bacteria and other eukaryotes. Interestingly, using HMGL enzyme assays, we found that rather than HMGL46, homodimeric recombinant HMGL35 is the active enzyme catalyzing acetyl-CoA and acetoacetate synthesis when incubated with (S)-HMG-CoA. This suggested that the plant-specific P100 peptide may inactivate HMGL according to specific physiological requirements. Therefore, we investigated whether the P100 peptide in HMGL46 alters its activity, possibly by modifying the HMGL46 structure. We found that induced expression of a cytosolic HMGL35 version in A. thaliana delays germination and leads to rapid wilting and chlorosis in mature plants. Our results suggest that in plants, P100-mediated HMGL inactivation outside of peroxisomes or mitochondria is crucial, protecting against potentially cytotoxic effects of HMGL activity while it transits to these organelles.
Assuntos
Hidroliases/genética , Hidroliases/metabolismo , Acetilcoenzima A/metabolismo , Acil Coenzima A/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Biologia Computacional/métodos , Citosol/metabolismo , Hidroximetilglutaril-CoA Sintase/metabolismo , Mitocôndrias/metabolismo , Peroxissomos/metabolismo , Plantas/genética , Plantas/metabolismo , Isoformas de Proteínas/genética , Homologia de Sequência de AminoácidosRESUMO
Infertility is a relatively common disorder of the reproductive system and remains unexplained in many cases. In vitro fertilization techniques have uncovered previously unrecognized infertility phenotypes, including oocyte maturation arrest, the molecular etiology of which remains largely unknown. We report two families affected by female-limited infertility caused by oocyte maturation failure. Positional mapping and whole-exome sequencing revealed two homozygous, likely deleterious variants in PATL2, each of which fully segregates with the phenotype within the respective family. PATL2 encodes a highly conserved oocyte-specific mRNP repressor of translation. Previous data have shown the strict requirement for PATL2 in oocyte-maturation in model organisms. Data gathered from the families in this study suggest that the role of PATL2 is conserved in humans and expand our knowledge of the factors that are necessary for female meiosis.
Assuntos
Proteínas de Ligação a DNA/genética , Infertilidade Feminina/genética , Infertilidade Feminina/patologia , Mutação , Oócitos/patologia , Adulto , Diferenciação Celular , Feminino , Fertilização in vitro , Humanos , Masculino , Meiose , Oócitos/metabolismo , Linhagem , Fenótipo , GravidezRESUMO
Helicobacter pylori infection represents a major risk factor for the development of gastric diseases and gastric cancer. The capability of H. pylori to inject the virulence factor cytotoxin-associated gene A (CagA) depends on a type IV secretion system (T4SS) encoded by the cag pathogenicity island (cagPAI). Further, infection by H. pylori activates the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in a T4SS-dependent manner but CagA-independent manner. Here we investigated the role of host cell receptors carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) and the bacterial adhesin HopQ in the activation of non-canonical NF-κB and CagA translocation into gastric epithelial cells. AGS cells express six of twelve CEACAMs found in humans. In HeLa cells, only CEACAM19 is expressed. We showed that deletion of hopQ attenuates the activation of non-canonical NF-κB only in AGS but not in HeLa cells. CagA translocation was in both cell lines affected by HopQ depletion, although to a much lesser extent in HeLa cells. Moreover, we observed a possible redundancy between the three HopQ-binding CEACAMs 1, 5 and 6 and their capacity to support non-canonical NF-κB activation. Our results illustrate that the interaction between HopQ and CEACAMs could promote the efficiency of the T4SS.
Assuntos
Antígenos de Neoplasias/genética , Proteínas de Bactérias/genética , Moléculas de Adesão Celular/genética , Infecções por Helicobacter/metabolismo , NF-kappa B/metabolismo , Sistemas de Secreção Tipo IV/genética , Antígenos de Bactérias/genética , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Células Epiteliais , Células HeLa , Helicobacter pylori/genética , HumanosRESUMO
Non-thermal food processing and replacement of chemical additives by natural antimicrobials are promising trends in the food industry. The objective of the present work was to evaluate the effect of a process which combines mild high hydrostatic pressure - HHP (200 and 300â¯MPa, 5â¯min, 10⯰C), phage Listex™ P100 and the bacteriocin pediocin PA-1 as a new non-thermal process for destruction of Listeria monocytogenes (104â¯CFUâ¯mL-1 or 107â¯CFUâ¯mL-1) in milk. For inoculum levels of 104â¯CFUâ¯mL-1, HHP combined with phage P100 eliminated L. monocytogenes immediately after pressurization. When L. monocytogenes was inoculated at levels of 107â¯CFUâ¯mL-1, a synergistic effect between phage P100, pediocin PA-1 and HHP (300â¯MPa) on the inactivation of L. monocytogenes was observed during storage of milk at 4⯰C. For non-pressure treated samples inoculated with phage or pediocin or both, L. monocytogenes counts decreased immediately after biocontrol application, but regrowth was observed in a few samples during storage. Phage particles were stable during refrigerated storage for seven days while pediocin PA-1 remained stable only during three days. Further studies will have to be performed to validate the findings of this work in specific applications (e.g. production of raw milk cheese).
Assuntos
Bacteriófagos/fisiologia , Conservação de Alimentos/métodos , Conservantes de Alimentos/farmacologia , Listeria monocytogenes/efeitos dos fármacos , Listeria monocytogenes/virologia , Leite/microbiologia , Pediocinas/farmacologia , Animais , Bovinos , Contagem de Colônia Microbiana , Conservação de Alimentos/instrumentação , Pressão Hidrostática , Listeria monocytogenes/química , Listeria monocytogenes/crescimento & desenvolvimentoRESUMO
To evaluate attentional processes to visual stimuli that do not require motor response, a study with evoked potentials was carried out on 17 children with attention deficit disorder predominantly inattentive (ADDH-I) and 15 controls between the ages of 7 and 11 years. The latency and localization of sources of the early visual evoked potentials P100 and N100 were analyzed during the performance of a visual oddball task (20% horizontal and 80% vertical lines) where the vertical lines did not require motor response. The results indicate that ADDH-I group process visual information that does not require motor response with a greater increase in brain activity and through the ventral temporal pathway, while the control group does so by means of the dorsal parietal stream. This neurobiological process of visual information processing by ventral temporal pathway of ADDH-I group could be due to alterations in emotional processes that directly influence visual recognition or as consequence of deficit in the control of attentional processes by the dorsal parietal pathway.
Para evaluar los procesos atencionales a estímulos visuales que no requieren repuesta motora, se llevó a cabo un estudio con potenciales evocados a 17 niños con trastornos del déficit de atención/ hiperactividad (TDAH-I) con predominio inatento y a 15 controles de edades entre 7 y 11 años. Se analizó la latencia y localización de fuentes de los potenciales evocados visuales tempranos P100 y N100 durante la realización de una tarea oddball visual (20% rayas horizontales y 80% verticales) en que las rayas verticales no exigían respuesta motora. Los resultados indican que los niños con TDAH-I procesan la información visual que no requiere respuesta motora con un mayor aumento de la actividad cerebral y mediante la vía temporal ventral mientras que el grupo control lo hace mediante la vía parietal dorsal. Este proceso neurobiológico de procesamiento de la información visual vía temporal ventral de los niños con TDAH-I podría deberse a alteraciones en los procesos emocionales que influyen directamente en el reconocimiento visual o a un déficit en el control de los procesos atencionales por parte de la vía parietal dorsal.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Potenciais Evocados Visuais/fisiologia , Atenção/fisiologia , Criança , Eletroencefalografia , Potenciais Evocados/fisiologia , Feminino , Humanos , Masculino , Lobo Parietal/fisiologia , Lobo Temporal/fisiologia , Percepção Visual/fisiologiaRESUMO
ABSTRACT: Objective To research the correlation between the visual acuity ratio and pattern reversal visual evoked potential ï¼PRVEPï¼ P100 waveform amplitude ratio of both eyes. Methods Forty-seven volunteers were selected, and the visual chart visual acuity of both eyes was measured. The visual acuity ratio of the eye with poor vision to the eye with better vision was calculated by five grade notation method. The amplitudes of P100 waveforms of both eyes were recorded respectively by using black-and-white checkerboard PRVEP and chosing 1°, 15' stimulating visual angle, and the ratio of amplitudes between the two eyes was also calculated. SPSS 20.0 software was used to analyze the correlation between the visual acuity ratio and the ratio of P100 waveform amplitudes between the two eyes. Return test and linear regression analysis with the binocular ratio of P100 waveform amplitudes as the independent variable ï¼xï¼ and the binocular visual acuity ratio as the dependent variable ï¼yï¼ were made. Results There was a positive correlation between the binocular visual acuity ratio and the ratio of P100 waveform amplitudes under 15' stimulating visual angle ï¼Pearson correlation coefficient was 0.62, P=0.000ï¼. The fitting linear regression equation was y=0.090 x+0.846 ï¼F=20.954, P=0.000ï¼. There was no significant correlation between the binocular ratio of visual acuity and the binocular ratio of P100 waveform amplitudes under 1° stimulating visual angle ï¼P>0.05ï¼. Results of return test showed that there was no statistical significance in the difference between visual acuity estimated by equation and actual detected visual acuity. Conclusion In forensic appraisal of monocular injury, fitting linear regression equation of binocular visual acuity ratio and the binocular ratio of P100 waveform amplitudes under 15' stimulating visual angle, is helpful for visual acuity level estimation of the injured eye to some extent.
Assuntos
Potenciais Evocados Visuais , Olho/fisiopatologia , Visão Ocular , Acuidade Visual , Humanos , Análise de RegressãoRESUMO
CO2 is a physiological gas normally produced in the body during aerobic respiration. Hypercapnia (elevated blood pCO2 >≈50 mm Hg) is a feature of several lung pathologies, e.g. chronic obstructive pulmonary disease. Hypercapnia is associated with increased susceptibility to bacterial infections and suppression of inflammatory signaling. The NF-κB pathway has been implicated in these effects; however, the molecular mechanisms underpinning cellular sensitivity of the NF-κB pathway to CO2 are not fully elucidated. Here, we identify several novel CO2-dependent changes in the NF-κB pathway. NF-κB family members p100 and RelB translocate to the nucleus in response to CO2 A cohort of RelB protein-protein interactions (e.g. with Raf-1 and IκBα) are altered by CO2 exposure, although others are maintained (e.g. with p100). RelB is processed by CO2 in a manner dependent on a key C-terminal domain located in its transactivation domain. Loss of the RelB transactivation domain alters NF-κB-dependent transcriptional activity, and loss of p100 alters sensitivity of RelB to CO2 Thus, we provide molecular insight into the CO2 sensitivity of the NF-κB pathway and implicate altered RelB/p100-dependent signaling in the CO2-dependent regulation of inflammatory signaling.
Assuntos
Dióxido de Carbono/imunologia , Hipercapnia/imunologia , Subunidade p52 de NF-kappa B/imunologia , Transdução de Sinais/imunologia , Fator de Transcrição RelB/imunologia , Células A549 , Animais , Humanos , Hipercapnia/genética , Hipercapnia/patologia , Camundongos , Subunidade p52 de NF-kappa B/genética , Domínios Proteicos , Transdução de Sinais/genética , Fator de Transcrição RelB/genética , Transcrição Gênica/genética , Transcrição Gênica/imunologiaRESUMO
OBJECTIVE: Using a "double-pulse" adaptation paradigm, in which two stimuli are presented in quick succession, this study examines the neural mechanisms underlying potentiation of the visual evoked potential (VEP) in visual snow syndrome. BACKGROUND: Visual snow is a persistent visual disturbance characterized by rapid flickering dots throughout the visual field. Like the related condition of migraine with aura, visual snow has been hypothesized to arise from abnormal neuronal responsiveness, as demonstrated by a lack of typical VEP habituation to repeated visual stimulation. Yet the exact neural mechanisms underlying this effect remain unclear. Previous "double-pulse" experiments suggest that typical VEP habituation reflects disruptive gamma-band (50-70 Hz) neural oscillations, possibly driven by inhibitory interneurons. Given that migraine has been associated with reduced cortical inhibition, we propose here that visual snow may likewise reflect diminished inhibitory activity, resulting in decreased gamma power following initial visual stimulation and concomitant potentiation of the subsequent VEP response. METHODS: We compared VEP responses to double-pulse adaptation in a 22-year-old man with a 2-year history of visual snow versus a group of age- and gender-matched controls (N = 5). The patient does not have a comorbid diagnosis of episodic migraine or migraine with aura, and controls had no personal or family history of migraine. RESULTS: In contrast to the pattern of habituation observed in controls, visual snow was associated with persistent potentiation of the VEP response. Consistent with our predictions, time-frequency analysis revealed reduced gamma-band power following the initial stimulus in visual snow relative to controls. CONCLUSIONS: These results support an antagonistic interplay between gamma power and rapid neural adaptation, shedding new light on the neural mechanisms of VEP potentiation in visual snow.
Assuntos
Ritmo Gama/fisiologia , Habituação Psicofisiológica/fisiologia , Transtornos da Visão/diagnóstico , Transtornos da Visão/etiologia , Estudos de Casos e Controles , Eletroencefalografia , Potenciais Evocados Visuais , Humanos , Masculino , Transtornos de Enxaqueca/complicações , Estimulação Luminosa , Adulto JovemRESUMO
According to longitudinal studies, most individuals with borderline personality disorder (BPD) achieve remission. Since BPD is characterized by disturbed emotion recognition, this study investigated behavioral and electrophysiological correlates of facial emotion classification and processing in remitted BPD. 32 women with remitted BPD (rBPD), 32 women with current BPD (cBPD), and 28 healthy women (HC) participated in an emotion classification paradigm comprising blends of angry and happy faces while behavioral and electroencephalographic (event-related potentials) data were recorded. rBPD demonstrated a convergence in behavior towards HC in terms of responses and reaction times. They evaluated maximally ambiguous faces more positively and exhibited faster reaction times when classifying predominantly happy faces compared to cBPD. Group × facial emotion interaction effects were found in early electrophysiological processes with post hoc tests indicating differences between rBPD and cBPD but not between rBPD and HC. However, BPD-like impairments were still found in rBPD in later processing (P300). Our results suggest a reduction in negativity bias in rBPD on the behavioral level and a normalization of earlier stages of facial processing on the neural level, while alterations in later, more cognitive processing do not remit. Early processing may be more state-like, while later impairments may be more trait-like. Further research may need to focus on these stable components.
Assuntos
Transtorno da Personalidade Borderline/fisiopatologia , Eletroencefalografia , Emoções/fisiologia , Potenciais Evocados/fisiologia , Expressão Facial , Adulto , Transtorno da Personalidade Borderline/psicologia , Mapeamento Encefálico , Emoções/classificação , Reconhecimento Facial , Feminino , Humanos , Estudos Longitudinais , Estimulação Luminosa , Psicometria , Tempo de Reação/fisiologia , Adulto JovemRESUMO
The application of lytic phages as biocontrol agents is emerging as a promising strategy towards elimination or reduction of foodborne pathogens in a variety of food products. This technology is particularly advantageous for minimally processed and ready-to-eat (RTE) foods. In this study, the potential use of Listex™ P100 combined with high hydrostatic pressure (HPP), to enhance the control of Listeria monocytogenes in food was evaluated. For that, the effect of three pressures (200, 300 or 400â¯MPa; 5â¯min, 10⯰C) on phage P100 stability was tested when inoculated in six different matrices: phosphate buffered saline (PBS, pH 7.4); apple juice (pH 3.41); orange/carrot nectar (pH 3.54); UHT whole milk (pH 6.73); and, two traditional Portuguese fermented products, "Serra da Estrela" cheese (pH 5.66) and "Alheira", a meat sausage (pH 6.07). The results showed that treatment at 400â¯MPa reduced phage titres to below the detection level in all matrices, whereas at milder pressures the survival of the phage was matrix dependent. "Alheira", "Serra da Estrela" cheese and UHT whole milk were shown to be baroprotective matrices that support phage P100 application in HHP up to 300â¯MPa; however, an accentuated phage inactivation was observed in apple and orange/carrot nectar, which may be related to the acidic pH values of these matrices. The initial phage load did not affect the inactivation rate during HHP processing (300â¯MPa, 5â¯min, 10⯰C) in PBS, cheese, sausage or milk matrices, and the phage titres were stable in these matrices during storage at 4⯰C for 28 days for milk and 60 days for "Alheira" and "Serra da Estrela" cheese. In addition, a baroprotective effect on phage stability was observed when PBS was supplemented with reducing sugars, dextrin, casein, and tween 80. In conclusion, at mild HHP treatment, phage P100 remained active in specific matrices and seems to present potential to be added in non-thermal inactivation of L. monocytogenes.
Assuntos
Bacteriófagos/fisiologia , Queijo/microbiologia , Fast Foods/microbiologia , Conservação de Alimentos/métodos , Sucos de Frutas e Vegetais/microbiologia , Listeria monocytogenes/virologia , Produtos da Carne/microbiologia , Leite/microbiologia , Animais , Contaminação de Alimentos/prevenção & controle , Conservação de Alimentos/instrumentação , Pressão Hidrostática , Listeria monocytogenes/fisiologiaRESUMO
For three decades now, ionic liquids (ILs), organic salts comprising only ions, have emerged as a new class of pharmaceuticals. Although recognition of the antimicrobial effects of ILs is growing rapidly, there is almost nothing known about their possible virucidal activities. This probably reflects the paucity of understanding virus inactivation. In this study, we performed a systematic analysis to determine the effect of specific structural motifs of ILs on three different biological test systems (viruses, bacteria and enzymes). Overall, the effects of 27 different ILs on two non-enveloped and one enveloped virus (P100, MS2 and Phi6), two Gram negative and one Gram positive bacteria (E. coli, P. syringae and L. monocytogenes) and one enzyme (Taq DNA polymerase) were investigated. Results show that while some ILs were virucidal, no clear structure activity relationships (SARs) could be identified for the non-enveloped viruses P100 and MS2. However, for the first time, a correlation has been demonstrated between the effects of ILs on enveloped viruses, bacteria and enzyme inhibition. These identified SARs serve as a sound starting point for further studies.
Assuntos
Antivirais/farmacologia , Vírus de DNA/efeitos dos fármacos , Líquidos Iônicos/farmacologia , Vírus de RNA/efeitos dos fármacos , Antivirais/química , Escherichia coli/efeitos dos fármacos , Humanos , Líquidos Iônicos/química , Listeria monocytogenes/efeitos dos fármacos , Pseudomonas syringae/efeitos dos fármacos , Relação Estrutura-Atividade , Taq Polimerase/efeitos dos fármacosRESUMO
The International Organization for Standardization (ISO) standard 16900-1:2014 specifies the use of sodium chloride (NaCl) and corn oil aerosols, and sulfur hexafluoride gas for measuring total inward leakage (TIL). However, a comparison of TIL between different agents is lacking. The objective of this study was to measure and compare TIL for respirators using corn oil and NaCl aerosols. TIL was measured with 10 subjects donning two models of filtering facepiece respirators (FFRs) including FFP1, N95, P100, and elastomeric half-mask respirators (ERs) in NaCl and corn oil aerosol test chambers, using continuous sampling methods. After fit testing with a PortaCount (TSI, Inc., St. Paul, MN) using the Occupational Safety and Health Administration (OSHA) protocol, five subjects were tested in the NaCl chamber first and then in the corn oil chamber, while other subjects tested in the reverse order. TIL was measured as a ratio of mass-based aerosol concentrations in-mask to the test chamber, while the subjects performed ISO 16900-1-defined exercises. The concentration of NaCl aerosol was measured using two flame photometers, and corn oil aerosol was measured with one light scattering photometer. The same instruments were used to measure filter penetration in both chambers using a Plexiglas setup. The size distribution of aerosols was determined using a scanning mobility particle sizer and charge was measured with an electrometer. Filter efficiency was measured using an 8130 Automated Filter Tester (TSI). Results showed the geometric mean TIL for corn oil aerosol for one model each of all respirator categories, except P100, were significantly (p < 0.05) greater than for NaCl aerosol. Filter penetration in the two test chambers showed a trend similar to TIL. The count median diameter was â¼82 nm for NaCl and â¼200 nm for corn oil aerosols. The net positive charge for NaCl aerosol was relatively larger. Both fit factor and filter efficiency influence TIL measurement. Overall, TIL determination with aerosols of different size distributions and charges using different methodologies may produce dissimilar results.