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1.
Multisens Res ; 37(3): 185-216, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38714316

RESUMO

The influence of landmarks, that is, nearby non-target stimuli, on spatial perception has been shown in multiple ways. These include altered target localization variability near landmarks and systematic spatial distortions of target localizations. Previous studies have mostly been conducted in the visual modality using temporary, artificial landmarks or the tactile modality with persistent landmarks on the body. Thus, it is unclear whether both landmark types produce the same spatial distortions as they were never investigated in the same modality. Addressing this, we used a novel tactile setup to present temporary, artificial landmarks on the forearm and systematically manipulated their location to either be close to a persistent landmark (wrist or elbow) or in between both persistent landmarks at the middle of the forearm. Initial data (Exp. 1 and Exp. 2) suggested systematic differences of temporary landmarks based on their distance from the persistent landmark, possibly indicating different distortions of temporary and persistent landmarks. Subsequent control studies (Exp. 3 and Exp. 4) showed this effect was driven by the relative landmark location within the target distribution. Specifically, landmarks in the middle of the target distribution led to systematic distortions of target localizations toward the landmark, whereas landmarks at the side led to distortions away from the landmark for nearby targets, and toward the landmark with wider distances. Our results indicate that experimental results with temporary landmarks can be generalized to more natural settings with persistent landmarks, and further reveal that the relative landmark location leads to different effects of the pattern of spatial distortions.


Assuntos
Percepção Espacial , Percepção do Tato , Humanos , Percepção Espacial/fisiologia , Feminino , Percepção do Tato/fisiologia , Masculino , Adulto Jovem , Adulto , Tato/fisiologia , Estimulação Física , Antebraço/fisiologia
2.
Psychol Health ; : 1-19, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38204380

RESUMO

OBJECTIVE: Since sleep is an important part of life and too little sleep can lead to disastrous consequences, it is important to look at the factors that may disturb healthy sleep. While procrastination and in particular bedtime procrastination is such a disruptive factor, self-compassion on the other side might be a protective factor. METHODS: For this reason, in this study, we took a closer look at the interplay between bedtime procrastination, self-compassion, as well as at the actual sleep outcomes in a longitudinal diary study over 1 week. Our assumption was that bedtime procrastination has a negative impact on sleep outcomes, yet self-compassion could be a protective factor buffering this influence. To enable comparability with a previous study, analyses of variance were carried out. RESULTS: Utilizing frequentist and Bayesian analyses, we found a consistent negative influence of bedtime procrastination and a positive influence of self-compassion on almost all sleep outcomes. While self-compassion did not entirely mitigate the effect of bedtime procrastination on sleep, its positive impact on sleep outcomes was evident. CONCLUSIONS: These findings highlight the significance of self-compassion and procrastination in relation to actual sleep behaviour, adding to the existing body of literature on sleep research.

3.
Exp Brain Res ; 242(3): 599-618, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38227008

RESUMO

The ability to inhibit an already initiated response is crucial for navigating the environment. However, it is unclear which characteristics make stop-signals more likely to be processed efficiently. In three consecutive studies, we demonstrate that stop-signal modality and location are key factors that influence reactive response inhibition. Study 1 shows that tactile stop-signals lead to better performance compared to visual stop-signals in an otherwise visual choice-reaction task. Results of Study 2 reveal that the location of the stop-signal matters. Specifically, if a visual stop-signal is presented at a different location compared to the visual go-signal, then stopping performance is enhanced. Extending these results, study 3 suggests that tactile stop-signals and location-distinct visual stop-signals retain their performance enhancing effect when visual distractors are presented at the location of the go-signal. In sum, these results confirm that stop-signal modality and location influence reactive response inhibition, even in the face of concurrent distractors. Future research may extend and generalize these findings to other cross-modal setups.


Assuntos
Atenção , Inibição Psicológica , Humanos , Tempo de Reação/fisiologia , Atenção/fisiologia , Desempenho Psicomotor/fisiologia
4.
Psychol Res ; 88(1): 148-155, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37369933

RESUMO

Representational momentum describes the typical overestimation of the final location of a moving stimulus in the direction of stimulus motion. While systematically observed in different sensory modalities, especially vision and audition, in touch, empirical findings indicate a mixed pattern of results, with some published studies suggesting the existence of the phenomenon, while others do not. In the present study, one possible moderating variable, the relative probabilities of different trial types, was explored in an attempt to resolve the seemingly contradictory findings in the literature. In some studies, only consistently moving target stimuli were presented and no representational momentum was observed, while other studies have included inconsistently moving target stimuli in the same experimental block, and observed representational momentum. Therefore, the present study was designed to systematically compare the localization of consistent target motion stimuli across two experimental blocks, for which either only consistent motion trials were presented, or else mixed with inconsistent target motion trials. The results indicate a strong influence of variations in the probability of different trial types on the occurrence of representational momentum. That is, representational momentum only occurred when both trial types (inconsistent and consistent target motion) were presented within one experimental block. The results are discussed in light of recent theoretical advancements in the literature, namely the speed prior account of motion perception.


Assuntos
Percepção de Movimento , Percepção do Tato , Humanos , Percepção Auditiva , Movimento (Física) , Tato , Ensaios Clínicos como Assunto
5.
J Neurophysiol ; 130(6): 1403-1413, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37910559

RESUMO

Target localization is influenced by the presence of additionally presented nontargets, termed landmarks. In both the visual and tactile modality, these landmarks led to systematic distortions of target localizations often resulting in a shift toward the landmark. This shift has been attributed to averaging the spatial memory of both stimuli. Crucially, everyday experiences often rely on multiple modalities, and multisensory research suggests that inputs from different senses are optimally integrated, not averaged, for accurate perception, resulting in more reliable perception of cross-modal compared with uni-modal stimuli. As this could also lead to a reduced influence of the landmark, we wanted to test whether landmark distortions would be reduced when presented in a different modality or whether landmark distortions were unaffected by the modalities presented. In two experiments (each n = 30) tactile or visual targets were paired with tactile or visual landmarks. Experiment 1 showed that targets were less shifted toward landmarks from the different than the same modality, which was more pronounced for tactile than for visual targets. Experiment 2 aimed to replicate this pattern with increased visual uncertainty to rule out that smaller localization shifts of visual targets due to low uncertainty had led to the results. Still, landmark modality influenced localization shifts for tactile but not visual targets. The data pattern for tactile targets is not in line with memory averaging but seems to reflect the effects of multisensory integration, whereas visual targets were less prone to landmark distortions and do not appear to benefit from multisensory integration.NEW & NOTEWORTHY In the present study, we directly tested the predictions of two different accounts, namely, spatial memory averaging and multisensory integration, concerning the degree of landmark distortions of targets across modalities. We showed that landmark distortions were reduced across modalities compared to distortions within modalities, which is in line with multisensory integration. Crucially, this pattern was more pronounced for tactile than for visual targets.


Assuntos
Percepção do Tato , Percepção Visual , Tato , Incerteza
6.
Atten Percept Psychophys ; 85(8): 2637-2654, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37821746

RESUMO

The biases affecting people's perception of dynamic stimuli are typically robust and strong for specific stimulus configurations. For example, representational momentum describes a systematic perceptual bias in the direction of motion for the final location of a moving stimulus. Under clearly defined stimulus configurations (e.g., specific stimulus identity, size, speed), for example, the frequently used "implied motion" trial sequence, for which a target is subsequently presented in a consistent direction and with a consistent speed, a displacement in motion direction is evidenced. The present study explores the potential influence of expectations regarding directional as well as speed consistencies on representational momentum, elicited by including other, inconsistently moving trial types within the same experimental block. A systematic representational momentum effect was observed when only consistent motion trials were presented. In contrast, when inconsistent target motion trials were mixed within the same block of experimental trials, the representational momentum effect decreased, or was even eliminated (Experiments 1 & 2). Detailed analysis indicated that this reflects a global (proportion of consistent and inconsistent motion trials within a particular experimental block), not local (preceding trial influencing actual trial) effect. Yet, additional follow-up studies (Experiments 3 & 4) support the idea that these changes in perceived location are strongly influenced by the overall stimulus speed statistics in the different experimental blocks. These results are discussed and interpreted in light of recent theoretical developments in the literature on motion perception that highlight the importance of expectations about stimulus speed for motion perception.


Assuntos
Percepção de Movimento , Humanos , Movimento (Física) , Viés
7.
Perception ; 52(10): 726-738, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37680125

RESUMO

Whether the direction of a hand motion that is congruent or incongruent with a concurrent target motion can influence representational momentum for that target was examined. Participants viewed a leftward or rightward moving target while moving their hand rightward, leftward, or not moving their hand. Prior studies of mental rotation found that congruency or incongruency of the direction of mental rotation and the direction of a concurrent physical rotation of a stimulus influenced mental rotation. As mental rotation and representational momentum each involve extrapolation of target motion, it could be predicted that congruency of the direction of hand motion and the direction of target motion might influence representational momentum of the target. Robust representational momentum occurred in all conditions, but there was no effect of congruency of hand motion and target motion, nor of the presence or absence of hand motion, on representational momentum. The results are consistent with a hypothesis that the generation of representational momentum involves sensory processes rather than motor processes.


Assuntos
Mãos , Sensação , Humanos , Movimento (Física)
8.
Atten Percept Psychophys ; 85(3): 596-612, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36229630

RESUMO

Top-down control over stimulus-driven attentional capture, as postulated by the contingent capture hypothesis, has been a topic of lively scientific debate for a number of years now. According to the latter hypothesis, a stimulus has to match the feature of a top-down established control set in order to be selected automatically. Today, research on the topic of contingent capture has focused mostly on the manipulation of only a single feature separating the target from the distractors (the selection feature). The research presented here examined the compilation of top-down attentional control sets having multiple selection features. We report three experiments in which the feature overlap between the distractor and the top-down sets was manipulated on different perceptual features (e.g., colour, orientation and location). Distractors could match three, two or one of the features of the top-down sets. In line with our hypotheses, the strength of the distractor interference effects decreased linearly as the feature overlap between the distractor and the participants' top-down sets decreased. These results therefore suggest a decline in the efficiency with which distractors involuntarily capture attention as the target-similarity decreases. The data support the idea of multi-feature attentional control sets and are discussed in light of prominent contemporary theories of visual attention.

9.
Exp Brain Res ; 241(1): 59-66, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36357591

RESUMO

Processing ambiguous situations is a constant challenge in everyday life and sensory input from different modalities needs to be integrated to form a coherent mental representation on the environment. The bouncing/streaming illusion can be studied to provide insights into the ambiguous perception and processing of multi-modal environments. In short, the likelihood of reporting bouncing rather than streaming impressions increases when a sound coincides with the moment of overlap between two moving disks. Neuroimaging studies revealed that the right posterior parietal cortex is crucial in cross-modal integration and is active during the bouncing/streaming illusion. Consequently, in the present study, we used transcranial direct current stimulation to stimulate this brain area. In the active stimulation conditions, a 9 cm2 electrode was positioned over the P4-EEG position and the 35 cm2 reference positioned over the left upper arm. The stimulation lasted 15 min. Each participant did the bouncing/streaming task three times: before, during and after anodal or sham stimulation. In a sample of N = 60 healthy, young adults, we found no influence of anodal tDCS. Bayesian analysis showed strong evidence against tDCS effects. There are two possible explanations for the finding that anodal tDCS over perceptual areas did not modulate multimodal integration. First, upregulation of multimodal integration is not possible using tDCS over the PPC as the integration process already functions at maximum capacity. Second, prefrontal decision-making areas may have overruled any modulated input from the PPC as it may not have matched their decision-making criterion and compensated for the modulation.


Assuntos
Ilusões , Estimulação Transcraniana por Corrente Contínua , Adulto Jovem , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Teorema de Bayes , Encéfalo/fisiologia , Lobo Parietal/fisiologia
10.
Exp Psychol ; 69(2): 61-74, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35726674

RESUMO

Representational Momentum and Representational Gravity describe systematic perceptual biases, occurring for the localization of the final location of a moving stimulus. While Representational Momentum describes the systematic overestimation along the motion trajectory (forward shift), Representational Gravity refers to a systematic localization bias in line with gravitational force (downward shift). Those phenomena are typically investigated in a laboratory setting, and while previous research has shown that online studies perform well for different task, motion perception outside of the laboratory was not focused to date. Therefore, one experiment was conducted in two different settings: in a typical, highly controlled laboratory setting and in an online setting of the participants' choosing. In both experiments, the two most common trial types, implied motion stimuli and continuously moving stimuli, were used, and the influence of classical velocity manipulations (by varying stimulus timing and distance) was assessed. The data pattern across both experiments was very similar, indicating a robustness of both phenomena and indicating that motion perception can very well be studied outside the classical laboratory setting, opening a feasible possibility to diversify access to motion perception experiments everywhere.


Assuntos
Percepção de Movimento , Viés , Gravitação , Humanos
11.
J Exp Psychol Gen ; 151(10): 2418-2436, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35389739

RESUMO

Our perception of moving stimuli is prone to systematic biases. Different biases, for example concerning the perceived speed, or spatial location, of a dynamic, moving stimulus, have consistently been reported in the literature. Different lines of experimental research, together with different theoretical explanations, have emerged analyzing and discussing these biases separately. In the present study, we propose a new theoretical account to unite various effects relating to dynamic/moving stimuli: The speed prior account. The perceived location of a stimulus is suggested to reflect the combination of the sensory input, which is associated with uncertainty, and a prior expectation concerning stimulus speed. Discrepancies between the prior speed expectation and the actual speed of a stimulus then result in a distortion of perceived stimulus speed, leading to the various perceptual biases that have been observed. In the present study, we demonstrate that this new theory can already account for robust data patterns currently unexplained in the literature, while we additionally directly test the predictions of the new speed prior account across four experiments. The influence of stimulus speed was manipulated in two visual as well as two tactile studies (all N = 30). The results reveal a clear data pattern, consistent with the speed prior account, as perceived onset and offset location reveal strong interdependencies. The implications and possible future questions for the perception of moving stimuli, in particular, and dynamic information, more generally, are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Assuntos
Percepção de Movimento , Humanos , Tato
12.
Cognition ; 219: 104978, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34864524

RESUMO

We introduce a new audio-visual illusion revealing the interplay between audio-visual integration and selective visual attention. This illusion involves two simultaneously moving objects that change their motion trajectory occasionally, but only the direction changes of one object are accompanied by spatially uninformative tones. We observed a selective increase in perceived object speed of the audio-visually synchronized object by measuring the point of subjective equality in a forced-choice paradigm. The illusory increase in perceived speed of the audio-visually synchronized object persisted when preventing eye movements. Using temporally matched color changes of the synchronized object also increased the perceived speed. Yet, using color changes of a surrounding frame instead of tones had no effect on perceived speed ruling out simple alertness explanations. Thus, in contrast to coinciding tones, visual coincidences only elicit illusory increases in perceived speed when the coincidence provided spatial information. Taken together, our pattern of results suggests that audio-visual synchrony attracts visual attention toward the coinciding visual object, leading to an increase in speed-perception and thus shedding new light on the interplay between attention and multisensory feature integration. We discuss potential limitations such as the choice of paradigm and outline prospective research question to further investigate the effect of audio-visual integration on perceived object speed.


Assuntos
Ilusões , Percepção de Movimento , Estimulação Acústica , Humanos , Estimulação Luminosa , Estudos Prospectivos , Percepção Visual
13.
Eur J Cancer ; 159: 182-193, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34773902

RESUMO

INTRODUCTION: Many cancer guidelines include sentinel lymph node (SLN) staging to identify microscopic metastatic disease. Current SLN analysis of melanoma patients is effective but has the substantial drawback that only a small representative portion of the node is sampled, whereas most of the tissue is discarded. This might explain the high clinical false-negative rate of current SLN diagnosis in melanoma. Furthermore, the quantitative assessment of metastatic load and microanatomical localisation might yield prognosis with higher precision. Thus, methods to analyse entire SLNs with cellular resolution apart from tedious sequential physical sectioning are required. PATIENTS AND METHODS: Eleven melanoma patients eligible to undergo SLN biopsy were included in this prospective study. SLNs were fixed, optically cleared, whole-mount stained and imaged using light sheet fluorescence microscopy (LSFM). Subsequently, compatible and unbiased gold standard histopathological assessment allowed regular patient staging. This enabled intrasample comparison of LSFM and histological findings. In addition, the development of an algorithm, RAYhance, enabled easy-to-handle display of LSFM data in a browsable histologic slide-like fashion. RESULTS: We comprehensively quantify total tumour volume while simultaneously visualising cellular and anatomical hallmarks of the associated SLN architecture. In a first-in-human study of 21 SLN of melanoma patients, LSFM not only confirmed all metastases identified by routine histopathological assessment but also additionally revealed metastases not detected by routine histology alone. This already led to additional therapeutic options for one patient. CONCLUSION: Our three-dimensional digital pathology approach can increase sensitivity and accuracy of SLN metastasis detection and potentially alleviate the need for conventional histopathological assessment in the future. GERMAN CLINICAL TRIALS REGISTER: (DRKS00015737).


Assuntos
Imageamento Tridimensional/métodos , Metástase Linfática/patologia , Melanoma/patologia , Microscopia de Fluorescência/métodos , Estadiamento de Neoplasias/métodos , Linfonodo Sentinela/patologia , Humanos , Metástase Linfática/diagnóstico
14.
Atten Percept Psychophys ; 83(5): 2256-2266, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33768482

RESUMO

Binding theories assume that features of stimuli and executed responses can be integrated together in one event file (Hommel, Visual Cognition, 5, 183-216, 1998; Hommel, Cognitive Sciences, 8, 494-500, 2004). Every reencounter with one or more of the stored features leads to an automatic retrieval of the previously constructed event file and hence of the response-even the repetition of a task-irrelevant distractor stimulus can retrieve a previously encoded response. This so-called distractor-response binding effect is typically investigated using a sequential prime-probe design that allows the orthogonal variation of response relation (response repetition vs. resporrevertnse change) and distractor relation (distractor repetition vs. distractor change), while probe response times and error rates are measured as dependent variable. Previous research has shown that task-relevant stimuli can be represented at different levels (e.g., perceptual and conceptual; see Henson et al., Trends in Cognitive Sciences, 18, 376-384, 2014), yet it is not clear at which level of representation distractor stimuli are processed. In the present study, we focused on the level of representation of response-irrelevant distractor stimuli. To this end, a crossmodal distractor-response binding paradigm was used that enables the differentiation between the perceptual and conceptual representation of the distractor by allowing the systematic repetition and change of conceptual distractor features independent of perceptual repetitions. The results suggest that the repetition of perceptual distractor features is indispensable for the initiation of the retrieval process while the sole repetition of conceptual distractor features is not sufficient to start the retrieval process.


Assuntos
Atenção , Cognição , Humanos , Tempo de Reação , Sensação
15.
Atten Percept Psychophys ; 83(5): 2113-2122, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33782912

RESUMO

The perception of dynamic objects is sometimes biased. For example, localizing a moving object after it has disappeared results in a perceptual shift in the direction of motion, a bias known as representational momentum. We investigated whether the temporal characteristics of an irrelevant, spatially uninformative vibrotactile stimulus bias the perceived location of a visual target. In two visuotactile experiments, participants judged the final location of a dynamic, visual target. Simultaneously, a continuous (starting with the onset of the visual target, Experiments 1 and 2) or brief (33-ms stimulation, Experiment 2) vibrotactile stimulus (at the palm of participant's hands) was presented, and the offset disparity between the visual target and tactile stimulation was systematically varied. The results indicate a cross-modal influence of tactile stimulation on the perceived final location of the visual target. Closer inspection of the nature of this cross-modal influence, observed here for the first time, reveals that the vibrotactile stimulus was likely just taken as a temporal cue regarding the offset of the visual target, but no strong interaction and combined processing of the two stimuli occurred. The present results are related to similar cross-modal temporal illusions and current accounts of multisensory perception, integration, and cross-modal facilitation.


Assuntos
Percepção de Movimento , Percepção do Tato , Sinais (Psicologia) , Humanos , Movimento (Física) , Estimulação Luminosa , Tato , Percepção Visual
16.
Atten Percept Psychophys ; 83(2): 776-789, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32514664

RESUMO

Charles W. Eriksen dedicated much of his research career to the field of cognitive psychology, investigating human information processing in those situations that required selection between competing stimuli. Together with his wife Barbara, he introduced the flanker task, which became one of the standard experimental tasks used by researchers to investigate the mechanisms underpinning selection. Although Eriksen himself was primarily interested in investigating visual selection, the flanker task was eventually adapted by other researchers to investigate human information processing and selection in a variety of nonvisual and multisensory situations. Here, we discuss the core aspects of the flanker task and interpret the evidence of the flanker task when used in crossmodal and multisensory settings. "Selection" has been a core topic of psychology for nearly 120 years. Nowadays, though, it is clear that we need to look at selection from a multisensory perspective-the flanker task, at least in its crossmodal and multisensory variants, is an important tool with which to investigate selection, attention, and multisensory information processing.


Assuntos
Atenção , Percepção Visual , Cognição , Humanos , Masculino
17.
Mol Brain ; 13(1): 124, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32928261

RESUMO

Glutamate toxicity is a pathomechanism that contributes to neuronal cell death in a wide range of acute and chronic neurodegenerative and neuroinflammatory diseases. Activation of the N-methyl-D-aspartate (NMDA)-type glutamate receptor and breakdown of the mitochondrial membrane potential are key events during glutamate toxicity. Due to its manifold functions in nervous system physiology, however, the NMDA receptor is not well suited as a drug target. To identify novel compounds that act downstream of toxic NMDA receptor signaling and can protect mitochondria from glutamate toxicity, we developed a cell viability screening assay in primary mouse cortical neurons. In a proof-of-principle screen we tested 146 natural products and 424 FDA-approved drugs for their ability to protect neurons against NMDA-induced cell death. We confirmed several known neuroprotective drugs that include Dutasteride, Enalapril, Finasteride, Haloperidol, and Oxybutynin, and we identified neuroprotective properties of Elvitegravir. Using live imaging of tetramethylrhodamine ethyl ester-labelled primary cortical neurons, we found that Elvitegravir, Dutasteride, and Oxybutynin attenuated the NMDA-induced breakdown of the mitochondrial membrane potential. Patch clamp electrophysiological recordings in NMDA receptor-expressing HEK293 cell lines and primary mouse hippocampal neurons revealed that Elvitegravir does not act at the NMDA receptor and does not affect the function of glutamatergic synapses. In summary, we have developed a cost-effective and easy-to-implement screening assay in primary neurons and identified Elvitegravir as a neuro- and mitoprotective drug that acts downstream of the NMDA receptor.


Assuntos
Antivirais/farmacologia , Aprovação de Drogas , Microscopia , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Quinolonas/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , United States Food and Drug Administration , Animais , Morte Celular/efeitos dos fármacos , Células Cultivadas , Channelrhodopsins/metabolismo , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Células HEK293 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Endogâmicos C57BL , N-Metilaspartato/farmacologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neuroproteção/efeitos dos fármacos , Optogenética , Receptores de AMPA/metabolismo , Receptores de Glutamato/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Sinapses/metabolismo , Estados Unidos
18.
Acta Neuropathol Commun ; 8(1): 135, 2020 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-32792006

RESUMO

Progressive multi-focal leukoencephalopathy (PML) is a potentially fatal encephalitis caused by JC polyomavirus (JCV). PML principally affects people with a compromised immune system, such as patients with multiple sclerosis (MS) receiving treatment with natalizumab. However, intrathecal synthesis of lipid-reactive IgM in MS patients is associated with a markedly lower incidence of natalizumab-associated PML compared to those without this antibody repertoire. Here we demonstrate that a subset of lipid-reactive human and murine IgMs induce a functional anti-viral response that inhibits replication of encephalitic Alpha and Orthobunyaviruses in multi-cellular central nervous system cultures. These lipid-specific IgMs trigger microglia to produce IFN-ß in a cGAS-STING-dependent manner, which induces an IFN-α/ß-receptor 1-dependent antiviral response in glia and neurons. These data identify lipid-reactive IgM as a mediator of anti-viral activity in the nervous system and provide a rational explanation why intrathecal synthesis of lipid-reactive IgM correlates with a reduced incidence of iatrogenic PML in MS.


Assuntos
Autoanticorpos/líquido cefalorraquidiano , Imunoglobulina M/líquido cefalorraquidiano , Leucoencefalopatia Multifocal Progressiva/imunologia , Lipídeos/imunologia , Esclerose Múltipla , Animais , Autoanticorpos/imunologia , Autoantígenos/imunologia , Humanos , Hospedeiro Imunocomprometido/imunologia , Imunoglobulina M/imunologia , Fatores Imunológicos/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/imunologia , Natalizumab/efeitos adversos , Ratos , Ratos Sprague-Dawley
19.
BMC Cancer ; 20(1): 650, 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32660441

RESUMO

BACKGROUND: The identification of pathologically altered neutrophil granulocyte migration patterns bears strong potential for surveillance and prognostic scoring of diseases. We recently identified a strong correlation between impaired neutrophil motility and the disease stage of myelodysplastic syndrome (MDS). Here, we apply this assay to study quantitively increased neutrophils of a patient suffering from a rare leukemia subtype, atypical chronic myeloid leukemia (aCML). METHODS: A 69-year-old male was analyzed in this study. Besides routine analyses, we purified the patient's neutrophils from peripheral whole blood and studied their migration behavior using time-lapse video microscopy in a standardized assay. These live cell migration analyses also allowed for the quantification of cell morphology. Furthermore, the cells were stained for the markers CD15, CD16, fMLPR, CXCR1 and CXCR2. RESULTS: Despite cytoreductive therapy with hydroxyurea, the patient's WBC and ANC were poorly controlled and severe dysgranulopoiesis with hypogranularity was observed. Neutrophils displayed strongly impaired migration when compared to healthy controls and migrating cells exhibited a more flattened-out morphology than control neutrophils. Because of a detected CSF3R (p.T618I) mutation and constitutional symptoms treatment with ruxolitinib was initiated. Within 1 week of ruxolitinib treatment, the cell shape normalized and remained indistinguishable from healthy control neutrophils. However, neutrophil migration did not improve over the course of ruxolitinib therapy but was strikingly altered shortly before a sinusitis with fever and bleeding from a gastric ulcer. Molecular work-up revealed that under ruxolitinib treatment, the CSF3R clone was depleted, yet the expansion of a NRAS mutated subclone was promoted. CONCLUSION: These results demonstrate the usefulness of neutrophil migration analyses to uncover corresponding alterations of neutrophil migration in rare myeloid neoplasms. Furthermore, in addition to monitoring migration the determination of morphological features of live neutrophils might represent a useful tool to monitor the effectiveness of therapeutic approaches.


Assuntos
Biomarcadores Tumorais/genética , Movimento Celular , Granulócitos/patologia , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/tratamento farmacológico , Neutrófilos/patologia , Pirazóis/efeitos adversos , Idoso , Estudos de Casos e Controles , Feminino , Granulócitos/efeitos dos fármacos , Granulócitos/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/patologia , Estudos Longitudinais , Masculino , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Nitrilas , Prognóstico , Pirimidinas
20.
Atten Percept Psychophys ; 82(5): 2618-2629, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32140935

RESUMO

After an object disappears, the vanishing point is shifted in the direction of motion, a phenomenon known as representational momentum. The present study focused on the relationship between motion information and spatial location in a crossmodal setting. In two visuotactile experiments, we studied how motion information in one sensory modality affects the perceived final location of a motion signal (congruent vs. incongruent left-right motion direction) in another modality. The results revealed a unidirectional crossmodal influence of motion information on spatial localization performance. While visual motion information influenced the perceived final location of the tactile stimulus, tactile motion information had no influence on visual localization. These results therefore extend the existing literature on crossmodal influences on spatial location and are discussed in relation to current theories of multisensory perception.


Assuntos
Percepção de Movimento , Movimento (Física) , Percepção do Tato , Adolescente , Adulto , Viés , Humanos , Masculino , Estimulação Luminosa , Adulto Jovem
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