RESUMEN
Researchers dispute the cause of errors in high Go, low No Go target detection tasks, like the Sustained Attention to Response Task (SART). Some researchers propose errors in the SART are due to perceptual decoupling, where a participant is unaware of stimulus identity. This lack of external awareness causes an erroneous response. Other researchers suggest the majority of the errors in the SART are instead due to response leniency, not perceptual decoupling. Response delays may enable a participant who is initially unaware of stimulus identity, perceptually decoupled, to become aware of stimulus identity, or perceptually recoupled. If, however, the stimulus presentation time is shortened to the minimum necessary for stimulus recognition and the stimulus is disrupted with a structured mask, then there should be no time to enable perception to recouple even with a response delay. From the perceptual decoupling perspective, there should be no impact of a response delay on performance in this case. Alternatively if response bias is critical, then even in this case a response delay may impact performance. In this study, we shortened stimulus presentation time and added a structured mask. We examined whether a response delay impacted performance in the SART and tasks where the SART's response format was reversed. We expected a response delay would only impact signal detection theory bias, c, in the SART, where response leniency is an issue. In the reverse formatted SART, since bias was not expected to be lenient, we expected no impact or minimal impact of a response delay on response bias. These predictions were verified. Response bias is more critical in understanding SART performance, than perceptual decoupling, which is rare if it occurs at all in the SART.
Asunto(s)
Atención , Desempeño Psicomotor , Tiempo de Reacción , Humanos , Atención/fisiología , Femenino , Masculino , Adulto Joven , Adulto , Tiempo de Reacción/fisiología , Desempeño Psicomotor/fisiología , Percepción Visual/fisiología , Adolescente , Estimulación Luminosa/métodosRESUMEN
Tolerance of mouse kidney allografts arises in grafts that develop regulatory tertiary lymphoid organs (rTLOs). Single-cell RNA-seq (scRNA-seq) data and adoptive transfer of alloreactive T cells after transplantation showed that cytotoxic CD8+ T cells are reprogrammed within the accepted graft to an exhausted/regulatory-like phenotype mediated by IFN-γ. Establishment of rTLOs was required because adoptive transfer of alloreactive T cells prior to transplantation results in kidney allograft rejection. Despite the presence of intragraft CD8+ cells with a regulatory phenotype, they were not essential for the induction and maintenance of kidney allograft tolerance since renal allotransplantation into CD8-KO recipients resulted in acceptance and not rejection. Analysis of scRNA-seq data from allograft kidneys and malignant tumors identified similar regulatory-like cell types within the T cell clusters and trajectory analysis showed that cytotoxic CD8+ T cells are reprogrammed into an exhausted/regulatory-like phenotype intratumorally. Induction of cytotoxic CD8+ T cell dysfunction of infiltrating cells appears to be a beneficial mechanistic pathway that protects the kidney allotransplant from rejection through a process we call "defensive tolerance." This pathway has implications for our understanding of allotransplant tolerance and tumor resistance to host immunity.
Asunto(s)
Trasplante de Riñón , Tolerancia al Trasplante , Animales , Ratones , Tolerancia al Trasplante/inmunología , Linfocitos T CD8-positivos/inmunología , Linfocitos T Citotóxicos/inmunología , Ratones Noqueados , Rechazo de Injerto/inmunología , Rechazo de Injerto/patología , Aloinjertos/inmunología , Interferón gamma/inmunología , Interferón gamma/genética , Interferón gamma/metabolismoRESUMEN
Objectives Iatrogenic injury to the internal carotid artery (ICA) is one of the most catastrophic complications of endoscopic sinus and skull base surgery. Previous research has shown that packing with a crushed muscle graft at the injury site can be an effective management technique to control bleeding and prevent the need for ICA sacrifice. Here, we describe a novel and readily available repair donor site-an autologous lateral tongue muscle patch. Design Three representative cases of a successful repair of ICA injuries using a lateral tongue muscle patch are included in this study. The graft measured approximately 2 × 3 cm and was taken from the lateral intrinsic tongue musculature. We describe the harvest of the graft, its advantages, and the details of operative repair. Results The lateral tongue provides a large and readily accessible source of muscle within the surgical field that can be quickly harvested during an endoscopic procedure. For the first case, an expanding parasellar ICA pseudoaneurysm was managed with a tongue muscle patch and nasal packing. In the second case, a cavernous ICA injury was sustained during craniopharyngioma resection. Case three involved an ICA injury during endonasal debridement of invasive fungal rhinosinusitis. None of the patients required embolization or neurovascular stenting. Postoperative angiograms and serial computed tomography angiograms showed complete resolution of the pseudoaneurysm, and the patients continued to do well at least 1 year after repair. Conclusion Lateral tongue muscle graft is an effective and efficient method to manage ICA injuries during endoscopic endonasal surgery. Advantages include the speed of harvest, donor site being readily accessible in the surgical field, and low donor site morbidity. It should be added to the repertoire of possible donor sites for addressing catastrophic sinonasal bleeding.
RESUMEN
In the current investigation, we modified the high Go, low No-Go Sustained Attention to Response Task (SART). Some researchers argue a commission error, an inappropriate response to a No-Go stimulus, in the SART is due to the participant being inattentive, or perceptually decoupled, during stimulus onset. Response delays in the SART reduce commission errors. A response delay may therefore enable a participant who is initially inattentive to recouple their attention in time to appropriately perceive the stimulus and withhold a response to a No-Go stimulus. However, shortening stimulus display duration in the SART should limit the possibility of the participant identifying the stimulus later, if they are initially not attending the stimulus. A response delay should not reduce commission errors if stimulus duration is kept to the minimum duration enabling stimulus recognition. In two experiments, we shortened stimulus onset to offset duration and added response delays of varying lengths. In both experiments, even when stimulus duration was shortened, response delays notably reduced commission errors if the delay was greater than 250 ms. In addition, using the Signal Detection Theory perspective in which errors of commission in the SART are due to a lenient response bias-trigger happiness, we predicted that response delays would result in a shift to a more conservative response bias in both experiments. These predictions were verified. The errors of commission in the SART may not be a measures of conscious awareness per se, but instead indicative of the level of participant trigger happiness-a lenient response bias.
Asunto(s)
Felicidad , Desempeño Psicomotor , Humanos , Desempeño Psicomotor/fisiología , Tiempo de Reacción/fisiología , Prevalencia , Inhibición PsicológicaRESUMEN
Selection of the correct start codon is critical for high-fidelity protein synthesis. In eukaryotes, this is typically governed by a multitude of initiation factors (eIFs), including eIF2·GTP that directly delivers the initiator tRNA (Met-tRNAi Met ) to the P site of the ribosome. However, numerous reports, some dating back to the early 1970s, have described other initiation factors having high affinity for the initiator tRNA and the ability of delivering it to the ribosome, which has provided a foundation for further work demonstrating non-canonical initiation mechanisms using alternative initiation factors. Here we provide a critical analysis of current understanding of eIF2A, eIF2D, and the MCT-1·DENR dimer, the evidence surrounding their ability to initiate translation, their implications in human disease, and lay out important key questions for the field. This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes Translation > Mechanisms Translation > Regulation.
Asunto(s)
Factores Eucarióticos de Iniciación , ARN de Transferencia de Metionina , Ribosomas , Humanos , Eucariontes , Factores de Iniciación de Péptidos , Ribosomas/genética , ARN , Factor 2 Eucariótico de IniciaciónAsunto(s)
Anopheles/genética , Anopheles/fisiología , Citogenética , Malaria/diagnóstico , África , Asia OccidentalRESUMEN
Traducido del documento mimeografiado WHO/Mal/83