On the limits of top-down control of visual selection

In the present study, observers viewed displays in which two equally salient color singletons were simultaneously present. Before each trial, observers received a word cue (e.g., the word red, or green) or a symbolic cue (a circle colored red or green) telling them which color singleton to select on the upcoming trial. Even though many theories of visual search predict that observers should be able to selectively attend the target color singleton, the results of the present study show that observers could not select the target singleton without interference from the irrelevant color singleton. The results indicate that the irrelevant color singleton captured attention. Only when the color of the target singleton remained the same from one trial to the next was selection perfect—an effect that is thought to be the result of passive automatic intertrial priming. The results of the present study demonstrate the limits of top-down attentional control

Evidence for a dissociation between the control of oculomotor capture and disengagement

The current study investigated whether capture of the eyes by a salient onset distractor and the disengagement of the eyes from that distractor are driven by the same or by different underlying control modes. A variant of the classic oculomotor capture task was used. Observers had to make a saccade to the only gray circle among red background circles. On some trials, a green (novel color), red (placeholder color) or gray (target color) distractor square was presented with sudden onset. Results showed that when participants reacted fast, oculomotor capture was primarily driven by bottom-up pop-out: both types of distractors (green and gray) that popped out among the red background elements showed more capture than a red distractor that did not pop-out. In contrast to initial capture, disengagement of the eyes from the distractor was driven by top-down target–distractor similarity effects. We also examined the time-course of this effect. The distractor could change from green to either the target or placeholder color. When the color change was early in time (30–40 ms after its onset), dwell times were strongly affected by the change, whereas the effect on oculomotor capture was weak. Importantly, a change occurring as early as 60–80 ms after distractor onset did neither affect capture nor dwell times, corroborating the assumption of parallel programming of saccades

Top-down contingent feature-specific orienting with and without awareness of the visual input

In the present article, the role of endogenous feature-specific orienting for conscious and unconscious vision is reviewed. We start with an overview of orienting. We proceed with a review of masking research, and the definition of the criteria of experimental protocols that demonstrate endogenous and exogenous orienting, respectively. Against this background of criteria, we assess studies of unconscious orienting and come to the conclusion that so far studies of unconscious orienting demonstrated endogenous feature-specific orienting. The review closes with a discussion of the role of unconscious orienting in action control

LRRK2 Biology from structure to dysfunction: research progresses, but the themes remain the same

Since the discovery of leucine-rich repeat kinase 2 (LRRK2) as a protein that is likely central to the aetiology of Parkinson's disease, a considerable amount of work has gone into uncovering its basic cellular function. This effort has led to the implication of LRRK2 in a bewildering range of cell biological processes and pathways, and probable roles in a number of seemingly unrelated medical conditions. In this review we summarise current knowledge of the basic biochemistry and cellular function of LRRK2. Topics covered include the identification of phosphorylation substrates of LRRK2 kinase activity, in particular Rab proteins, and advances in understanding the activation of LRRK2 kinase activity via dimerisation and association with membranes, especially via interaction with Rab29. We also discuss biochemical studies that shed light on the complex LRRK2 GTPase activity, evidence of roles for LRRK2 in a range of cell signalling pathways that are likely cell type specific, and studies linking LRRK2 to the cell biology of organelles. The latter includes the involvement of LRRK2 in autophagy, endocytosis, and processes at the trans-Golgi network, the endoplasmic reticulum and also key microtubule-based cellular structures. We further propose a mechanism linking LRRK2 dimerisation, GTPase function and membrane recruitment with LRRK2 kinase activation by Rab29. Together these data paint a picture of a research field that in many ways is moving forward with great momentum, but in other ways has not changed fundamentally. Many key advances have been made, but very often they seem to lead back to the same places

Mixed signals: The effect of conflicting reward- and goal-driven biases on selective attention

© 2017, The Author(s). Attentional selection depends on the interaction between exogenous (stimulus-driven), endogenous (goal-driven), and selection history (experience-driven) factors. While endogenous and exogenous biases have been widely investigated, less is known about their interplay with value-driven attention. The present study investigated the interaction between reward-history and goal-driven biases on perceptual sensitivity (d’) and response time (RT) in a modified cueing paradigm presenting two coloured cues, followed by sinusoidal gratings. Participants responded to the orientation of one of these gratings. In Experiment 1, one cue signalled reward availability but was otherwise task irrelevant. In Experiment 2, the same cue signalled reward, and indicated the target’s most likely location at the opposite side of the display. This design introduced a conflict between reward-driven biases attracting attention and goal-driven biases directing it away. Attentional effects were examined comparing trials in which cue and target appeared at the same versus opposite locations. Two interstimulus interval (ISI) levels were used to probe the time course of attentional effects. Experiment 1 showed performance benefits at the location of the reward-signalling cue and costs at the opposite for both ISIs, indicating value-driven capture. Experiment 2 showed performance benefits only for the long ISI when the target was at the opposite to the reward-associated cue. At the short ISI, only performance costs were observed. These results reveal the time course of these biases, indicating that reward-driven effects influence attention early but can be overcome later by goal-driven control. This suggests that reward-driven biases are integrated as attentional priorities, just as exogenous and endogenous factors.This research was supported by an ERC advanced grant [ERC-2012-AdG–323413 Jan Theeuwes

Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling

Following endocytosis into the endosomal network, integral membrane proteins undergo sorting for lysosomal degradation or are retrieved and recycled back to the cell surface. Here we describe the discovery of an ancient and conserved multiprotein complex that orchestrates cargo retrieval and recycling and, importantly, is biochemically and functionally distinct from the established retromer pathway. We have called this complex 'retriever'; it is a heterotrimer composed of DSCR3, C16orf62 and VPS29, and bears striking similarity to retromer. We establish that retriever associates with the cargo adaptor sorting nexin 17 (SNX17) and couples to CCC (CCDC93, CCDC22, COMMD) and WASH complexes to prevent lysosomal degradation and promote cell surface recycling of α5β1 integrin. Through quantitative proteomic analysis, we identify over 120 cell surface proteins, including numerous integrins, signalling receptors and solute transporters, that require SNX17-retriever to maintain their surface levels. Our\ua0identification of retriever establishes a major endosomal retrieval and recycling pathway

Has the Rate of CD4 Cell Count Decline before Initiation of Antiretroviral Therapy Changed over the Course of the Dutch HIV Epidemic among MSM?

Introduction:Studies suggest that the HIV-1 epidemic in the Netherlands may have become more virulent, leading to faster disease progression if untreated. Analysis of CD4 cell count decline before antiretroviral therapy (ART) initiation, a surrogate marker for disease progression, may be hampered by informative censoring as ART initiation is more likely with a steeper CD4 cell count decline.Methods:Development of CD4 cell count from 9 to 48 months after seroconversion was analyzed using a mixed-effects model and 2 models that jointly modeled CD4 cell counts and time to censoring event (start ART