Characterization of envelope function of transmitted viruses circulating in Mbeya, Tanzania, and its impact on disease progression

An understanding of the biological characteristics of transmitted viruses provides important insights into HIV pathogenesis and informs vaccine development. The aim of the study was to characterize env function of transmitted viruses and its role in disease progression

V I R O L O G Y More than efficacy revealed by single-cell analysis of antiviral therapeutics

Because many aspects of viral infection dynamics and inhibition are governed by stochastic processes, single-cell analysis should provide more information than approaches using population averaging. We have developed a microfluidic device composed of ~6000 wells, with each well containing a microstructure to capture single, infected cells replicating an enterovirus expressing a fluorescent reporter protein. We have used this system to characterize enterovirus inhibitors with distinct mechanisms of action. Single-cell analysis reveals that each class of inhibitor interferes with the viral infection cycle in a manner that can be distinguished by principal component analysis. Single-cell analysis of antiviral candidates not only reveals efficacy but also facilitates clustering of drugs with the same mechanism of action and provides some indication of the ease with which resistance will develop

Beneficial HLA-mediated viral polymorphisms on the transmitted virus additively influence disease progression in HIV-1, subtype C infection

Transmitted viral factors have been shown to affect disease progression but whether infection with viruses carrying beneficial HLA-mediated escape polymorphisms affects disease progression in HLA-mismatched participants remains controversial

Temporal Brain Dynamics of Multiple Object Processing: The Flexibility of Individuation

The ability to process concurrently multiple visual objects is fundamental for a coherent perception of the world. A core component of this ability is the simultaneous individuation of multiple objects. Many studies have addressed the mechanism of object individuation but it remains unknown whether the visual system mandatorily individuates all relevant elements in the visual field, or whether object indexing depends on task demands. We used a neural measure of visual selection, the N2pc component, to evaluate the flexibility of multiple object individuation. In three ERP experiments, participants saw a variable number of target elements among homogenous distracters and performed either an enumeration task (Experiment 1) or a detection task, reporting whether at least one (Experiment 2) or a specified number of target elements (Experiment 3) was present. While in the enumeration task the N2pc response increased as a function of the number of targets, no such modulation was found in Experiment 2, indicating that individuation of multiple targets is not mandatory. However, a modulation of the N2pc similar to the enumeration task was visible in Experiment 3, further highlighting that object individuation is a flexible mechanism that binds indexes to object properties and locations as needed for further object processing

Single-Cell Virology: On-Chip Investigation of Viral Infection Dynamics

We have developed a high-throughput, microfluidics-based platform to perform kinetic analysis of viral infections in individual cells. We have analyzed thousands of individual poliovirus infections while varying experimental parameters, including multiplicity of infection, cell cycle, viral genotype, and presence of a drug. We make several unexpected observations masked by population-based experiments: (1) viral and cellular factors contribute uniquely and independently to viral infection kinetics; (2) cellular factors cause wide variation in replication start times; and (3) infections frequently begin later and replication occurs faster than predicted by population measurements. We show that mutational load impairs interaction of the viral population with the host, delaying replication start times and explaining the attenuated phenotype of a mutator virus. We show that an antiviral drug can selectively extinguish the most-fit members of the viral population. Single-cell virology facilitates discovery and characterization of virulence determinants and elucidation of mechanisms of drug action eluded by population methods. Guo et al. use a microfluidics device installed on a fluorescence microscope to monitor the kinetics of viral infection in single cells. Between-cell variation in outcomes of infection exists at all phases of the life cycle. Cellular gene expression governs the eclipse phase; viral genetics govern replication rate and yield

Exogenous spatial precuing reliably modulates object processing but not object substitution masking

Object substitution masking (OSM) is used in behavioral and imaging studies to investigate processes associated with the formation of a conscious percept. Reportedly, OSM occurs only when visual attention is diffusely spread over a search display or focused away from the target location. Indeed, the presumed role of spatial attention is central to theoretical accounts of OSM and of visual processing more generally (Di Lollo, Enns, & Rensink, Journal of Experimental Psychology: General 129:481–507, 2000). We report a series of five experiments in which valid spatial precuing is shown to enhance the ability of participants to accurately report a target but, in most cases, without affecting OSM. In only one experiment (Experiment 5) was a significant effect of precuing observed on masking. This is in contrast to the reliable effect shown across all five experiments in which precuing improved overall performance. The results are convergent with recent findings from Argyropoulos, Gellatly, and Pilling (Journal of Experimental Psychology: Human Perception and Performance 39:646–661, 2013), which show that OSM is independent of the number of distractor items in a display. Our results demonstrate that OSM can operate independently of focal attention. Previous claims of the strong interrelationship between OSM and spatial attention are likely to have arisen from ceiling or floor artifacts that restricted measurable performance

Regulation of S1PR2 by the EBV oncogene LMP1 in aggressive ABC subtype diffuse large B cell lymphoma.

The Epstein-Barr virus (EBV) is found almost exclusively in the activated B cell (ABC) subtype of diffuse large B cell lymphoma (DLBCL), yet its contribution to this tumour remains poorly understood. We have focussed on the EBV-encoded latent membrane protein-1 (LMP1), a constitutively activated CD40 homologue expressed in almost all EBV-positive DLBCL and which can disrupt germinal centre (GC) formation and drive lymphomagenesis in mice. Comparison of the transcriptional changes that follow LMP1 expression with those that follow transient CD40 signalling in human GC B cells enabled us to define pathogenic targets of LMP1 aberrantly expressed in ABC-DLBCL. These included the down-regulation of S1PR2, a sphingosine-1-phosphate (S1P) receptor that is transcriptionally down-regulated in ABC-DLBCL, and when genetically ablated leads to DLBCL in mice. Consistent with this we found that LMP1-expressing primary ABC-DLBCL were significantly more likely to lack S1PR2 expression than were LMP1-negative tumours. Furthermore, we showed that the down-regulation of S1PR2 by LMP1 drives a signalling loop leading to constitutive activation of the phosphatidylinositol-3-kinase (PI3-K) pathway. Finally, core LMP1-PI3-K targets were enriched for lymphoma-related transcription factors and genes associated with shorter overall survival in patients with ABC-DLBCL. Our data identify a novel function for LMP1 in aggressive DLBCL

Visual Working Memory Capacity Does Not Modulate the Feature-Based Information Filtering in Visual Working Memory

Background: The limited capacity of visual working memory (VWM) requires us to select the task relevant information and filter out the irrelevant information efficiently. Previous studies showed that the individual differences in VWM capacity dramatically influenced the way we filtered out the distracters displayed in distinct spatial-locations: low-capacity individuals were poorer at filtering them out than the high-capacity ones. However, when the target and distracting information pertain to the same object (i.e., multiple-featured object), whether the VWM capacity modulates the featurebased filtering remains unknown. Methodology/Principal Findings: We explored this issue mainly based on one of our recent studies, in which we asked the participants to remember three colors of colored-shapes or colored-landolt-Cs while using two types of task irrelevant information. We found that the irrelevant high-discriminable information could not be filtered out during the extraction of VWM but the irrelevant fine-grained information could be. We added 8 extra participants to the original 16 participants and then split the overall 24 participants into low- and high-VWM capacity groups. We found that regardless of the VWM capacity, the irrelevant high-discriminable information was selected into VWM, whereas the irrelevant fine-grained information was filtered out. The latter finding was further corroborated in a second experiment in which the participants were required to remember one colored-landolt-C and a more strict control was exerted over the VWM capacity

Dissociated Mechanisms of Extracting Perceptual Information into Visual Working Memory

The processing mechanisms of visual working memory (VWM) have been extensively explored in the recent decade. However, how the perceptual information is extracted into VWM remains largely unclear. The current study investigated this issue by testing whether the perceptual information was extracted into VWM via an integrated-object manner so that all the irrelevant information would be extracted (object hypothesis), or via a feature-based manner so that only the target-relevant information would be extracted (feature hypothesis), or via an analogous processing manner as that in visual perception (analogy hypothesis).High-discriminable information which is processed at the parallel stage of visual perception and fine-grained information which is processed via focal attention were selected as the representatives of perceptual information. The analogy hypothesis predicted that whereas high-discriminable information is extracted into VWM automatically, fine-grained information will be extracted only if it is task-relevant. By manipulating the information type of the irrelevant dimension in a change-detection task, we found that the performance was affected and the ERP component N270 was enhanced if a change between the probe and the memorized stimulus consisted of irrelevant high-discriminable information, but not if it consisted of irrelevant fine-grained information.We conclude that dissociated extraction mechanisms exist in VWM for information resolved via dissociated processes in visual perception (at least for the information tested in the current study), supporting the analogy hypothesis