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Working memory (WM) has been a major focus of cognitive science and neuroscience for the past 50 years. While most WM research has centered on the mechanisms of objects, there has been a lack of investigation into the cognitive and neural mechanisms of events, which are the building blocks of our experience. Employing confirmatory factor analysis and resting-state and task fMRI, our study demonstrated for the first time that events have an independent storage space within WM, known as the event cache, with distinct neural correlates compared to object storage in WM. The cerebellar network was found to be the most essential network for event cache, with the left cerebellum Crus I being particularly involved in encoding and maintaining events. Our findings shed critical light on the neuropsychological mechanism of WM by revealing event cache as an independent sub-component of WM and encourage the reconsideration of theoretical models for WM.

Visual working memory (WM) plays a pivotal role in integrating fragments into meaningful units, but no study has addressed how visual WM integration takes place in children. The current study examined whether WM integration emerges once preschoolers master Gestalt cue and can retain two representations in WM (automatic integration hypothesis), or still needs time to mature (maturation-of-integration hypothesis). Four experiments (N = 168, 81 females, 4- to 6-year-olds, Chinese, in Hangzhou, China, from 2016.10 to 2021.11) were conducted. Although 4-year-olds can retain two objects in WM and benefit from Gestalt cues in simultaneous display (Cohen's ds gt;1.00), they failed when memory arrays were presented sequentially. Meanwhile, 5- and 6-year-olds consistently demonstrated WM integration ability (all Cohen's ds gt;0.69), supporting the maturation-of-integration hypothesis.

Working memory (WM) has a limited capacity; however, this limitation can be mitigated by selecting individual items from the set currently held in WM for prioritization. The selection mechanism underlying this prioritization ability is referred to as the focus of attention (FOA) in WM. Although impressive progress has been achieved in recent years, a fundamental question remains unclear: Do perception and WM share one FOA? In the current study, we investigated the hypothesis that only a perceptual task tapping object-based attention can divert the FOA in WM. We adopted a retro-cue WM paradigm and inserted a perceptual task after the offset of the cue. Critically, we manipulated the type of attention (object-based attention in Experiments 1-3, feature-based attention in Experiment 4, and spatial attention in Experiment 5) consumed by the perceptual task. We found that participants were able to prioritize a retro-cued representation in WM, and the retro-cue benefit on memory accuracy was intact regardless of the perceptual task. Critically, the retro-cue benefit on the response time of WM task was significantly reduced only after an object-based attention perceptual task (Experiments 1, 2, 3a, and 3b), while remaining constant after a feature-based attention (Experiment 4) or spatial attention (Experiment 5) perceptual task. These results suggest that WM and perception share an object-based FOA, and an object-based attention perceptual task can divert the FOA in WM. Meanwhile, the current study further confirms that sustained attention is not necessary for selective maintenance in WM. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Working memory (WM) is essential for cognition, but the underlying neural mechanisms remain elusive. From a hierarchical processing perspective, this paper proposed and tested a hypothesis that a domain-general network at the top of the WM hierarchy can interact with distinct domain-preferential intermediate circuits to support WM. Employing a novel N-back task, we first identified the posterior superior temporal gyrus (pSTG), middle temporal area (MT), and postcentral gyrus (PoCG) as intermediate regions for biological motion and shape motion processing, respectively. Using further psychophysiological interaction analyses, we delineated a frontal–parietal network (FPN) as the domain-general network. These results were further verified and extended by a delayed match to sample (DMS) task. Although the WM load-dependent and stimulus-free activations during the DMS delay phase confirm the role of FPN as a domain-general network to maintain information, the stimulus-dependent activations within this network during the DMS encoding phase suggest its involvement in the final stage of the hierarchical processing chains. In contrast, the load-dependent activations of intermediate regions in the N-back task highlight their further roles beyond perception in WM tasks. These results provide empirical evidence for a hierarchical processing model of WM and may have significant implications for WM training.

Formaldehyde (FA) has long been considered as a toxin and carcinogen due to its damaging effects to biological macromolecules, but its beneficial roles have been increasingly appreciated lately. Real-time monitoring of this reactive molecule in living systems is highly desired in order to decipher its physiological and/or pathological functions, but a genetically encoded FA sensor is currently lacking. We herein adopt a structure-based study of the underlying mechanism of the FA-responsive transcription factor HxlR from Bacillus subtilis, which shows that HxlR recognizes FA through an intra-helical cysteine-lysine crosslinking reaction at its N-terminal helix α1, leading to conformational change and transcriptional activation. By leveraging this FA-induced intra-helical crosslinking and gain-of-function reorganization, we develop the genetically encoded, reaction-based FA sensor—FAsor, allowing spatial-temporal visualization of FA in mammalian cells and mouse brain tissues.

It has been suggested that retaining bindings in working memory (WM) requires more object-based attention than retaining constituent features. Recent studies have found that when memorized stimuli are presented sequentially, the most recent stimulus is in a highly accessible privileged state such that it is retained in a relatively automatic and resource-free manner, whereas the other stimuli are in a non-privileged state. The current study investigated whether the activation states of WM modulate the role of object-based attention in retaining bindings in WM. To address this question, we presented three colored shapes sequentially and added a transparent-motion task (Experiment 1) or a mental rotation task (Experiment 2) into the WM maintenance phase to consume object-based attention. We consistently found that consuming object-based attention led to a larger impairment to bindings relative to constituent features, which is independent of the WM activation states, suggesting that object-based attention is critical in retaining bindings in WM across activation states of WM.

The capacity of visual working memory (VWM) is found to be extremely limited. Past research shows that VWM can be facilitated by Gestalt principles of grouping, however, it remains controversial whether factors like the type of Gestalt principles, the characteristics of stimuli and the nature of experimental design could affect the beneficial effect of grouping. In particular, studies have shown that perceptual grouping could improve memory performance for a feature that is relevant for grouping, but it is unclear whether the same improvement exists for a feature that is irrelevant for grouping. In this article, an empirical study and a meta-analytic study were conducted to investigate the effect of perceptual grouping on VWM. In the empirical study, we examined the grouping effect by employing a Kanizsa illusion in which memory items were grouped by illusory contour. We found that the memory performance was improved for the grouped items even though the tested feature was grouping irrelevant, and the improvement was not significantly different from the effect of grouping by physical connectedness or by solid occlusion. In the meta-analytic study, we systematically and quantitatively examined the effect of perceptual grouping on VWM by pulling the results from all eligible studies, and found that the beneficial grouping effect was robust but the magnitude of the effect can be affected by several moderators. Factors like the types of grouping methods, the duration and the layout of the memory display, and the characteristics of the tested feature moderated the grouping effect, whereas whether employing a cue or a verbal suppression task did not. Our study suggests that the underlying mechanism of the grouping benefit may be distinct with regard to grouping relevancy of the to-be-stored feature. The grouping effect on VWM may be independent of attention for a grouping relevant feature, but may rely on attentional prioritization for a grouping irrelevant feature.

Temporal and reversible control over protein and cell conjugations holds great potential for traceless release of antibody-drug conjugates (ADCs) on tumor sites as well as on-demand altering or removal of targeting elements on cell surface. We herein developed a bioorthogonal and traceless releasable reaction on proteins and intact cells to fulfill such purposes. A systematic survey of transition metals in catalyzing the bioorthogonal cleavage reactions revealed that copper complexes such as Cu(I)-BTTAA and dual-substituted propargyl (dsPra) or propargyloxycarbonyl (dsProc) moieties offered a bioorthogonal releasable pair for reversible blockage and rescue of primary amines and phenol alcohols on small molecule drugs, protein side chains, as well as intact cell surface. For proof-of-concept, we employed such Cu(I)-BTTAA/dsProc and Cu(I)-BTTAA/dsPra pairs as a "traceless linker" strategy to construct cleavable ADCs to unleash cytotoxic compounds on cancer cells in situ and as a "reversible modification" strategy for cell surface engineering. Furthermore, by coupling with the genetic code expansion strategy, we site-specifically modulated ligand-receptor interactions on live cell membranes. Together, our work expanded the transition-metal-mediated bioorthogonal cleavage tool kit from terminal decaging to internal-linker breakage, which offered a temporal and reversible conjugation strategy on therapeutic proteins and cells.

Chemical de-caging has emerged as an attractive strategy for gain-of-function study of proteins via small-molecule reagents. The previously reported chemical de-caging reactions have been largely centered on liberating the side chain of lysine on a given protein. Herein, we developed an allene-based caging moiety and the corresponding palladium de-caging reagents for chemical rescue of tyrosine (Tyr) activity on intracellular proteins. This bioorthogonal de-caging pair has been successfully applied to unmask enzymatic Tyr sites (e.g., Y671 on Taq polymerase and Y728 on Anthrax lethal factor) as well as the post-translational Tyr modification site (Y416 on Src kinase) in vitro and in living cells. Our strategy provides a general platform for chemical rescue of Tyr-dependent protein activity inside cells.

We developed an in vitro DNA detection system using a pair of dCas9 proteins linked to split halves of luciferase. Luminescence was induced upon colocalization of the reporter pair to a ∼44 bp target sequence defined by sgRNAs. We used the system to detect Mycobacterium tuberculosis DNA with high specificity and sensitivity. The reprogrammability of dCas9 was further leveraged in an array design that accesses sequence information across the entire genome.

Visual working memory (VWM) is a cognitive memory buffer for temporarily holding, processing, and manipulating visual information. Previous studies have demonstrated mixed results of the effect of depth perception on VWM, with some showing a beneficial effect while others not. In this study, we employed an adapted change detection paradigm to investigate the effects of two depth cues, binocular disparity and relative size. The memory array consisted of a set of pseudo-randomly positioned colored items, and the task was to judge whether the test item was changed compared to the memory item after a retention interval. We found that presenting the items in stereoscopic depth alone hardly affected VWM performance. When combining the two coherent depth cues, a significant larger VWM capacity of the perceptually closer-in-depth items was observed than that of the farther items, but the capacity for the two-depth-planes condition was not significantly different from that for the one-plane condition. Conflicting the two depth cues resulted in cancelling the beneficial effect of presenting items at a closer depth plane. The results indicate that depth perception could affect VWM, and the visual system may have an advantage in maintaining closer-in-depth objects in working memory.