The visual system can flexibly adjust attentional deployment to match task demands, but whether observers can proactively modulate the spatial scope of attention based on expectations about upcoming search difficulty remains unclear. According to the zoom lens model, attention can narrow or broaden its spatial extent, with narrower focus enhancing processing efficiency, a mechanism that would benefit target discrimination in crowded displays. We tested whether observers adjust attentional scope when expecting sparse versus dense search arrays by combining spatial cueing with block-wise manipulations of display density expectations. Participants performed a visual search task in which endogenous cues predicted target location, while blocks predominantly contained either sparse (1 target, 3 distractors) or dense (1 target, 7 distractors) displays. We applied inverted encoding models to broadband EEG data to reconstruct spatial channel tuning functions, enabling precise characterization of both the locus and breadth of attentional deployment. Behaviorally, expecting difficult searches selectively improved accuracy at cued locations without costs elsewhere. Consistent with this selective benefit, neural measurements revealed that expectancy enhanced the amplitude of spatially selective responses at the attended location but did not alter tuning width. These findings demonstrate that expectations about search difficulty modulate attention through gain-based signal enhancement rather than adjustments to spatial scope, revealing that preparatory attentional control operates via amplitude modulation within a stable spatial focus. This mechanism complements reactive attentional adjustments and provides an efficient means for the visual system to optimize processing under predictable task demands.
Aberrant WNT/β-catenin signaling drives tumorigenesis and metastasis in cancer. Although enzymatic inhibitors of tankyrase (TNKS) effectively block AXIN degradation and stabilize the β-catenin destruction complex (DC), they have demonstrated limited efficacy in various colorectal cancer (CRC) models. Here, we demonstrate that, unexpectedly, the induction of AXIN puncta represents a major barrier to achieving therapeutic efficacy. Mechanistically, catalytic inhibition of TNKS prevents TNKS turnover and drives its accumulation in the DC, wherein the scaffolding function of TNKS induces AXIN puncta formation, rigidifies the DC, and impedes β-catenin turnover. Chemically induced degradation of TNKS overcomes this limitation by stabilizing AXIN without puncta formation, providing a deeper suppression of the WNT/β-catenin pathway activity and the proliferation of CRC cells harboring dysfunctional APC mutations. Collectively, these findings provide an explanation for the unsatisfactory outcomes of drugging the WNT/β-catenin signaling pathway by TNKS inhibitors and highlight TNKS degradation as a promising approach to treat WNT/β-catenin-driven CRC.
Emotions are based on evolutionarily conserved building blocks (‘emotion primitives’) that are present across mammals. Whether these building blocks are found in insects is largely undefined. Here, we employ the open field test (OFT) in Drosophila and focus on wall-following and total walking activity as behavioural indicators of emotion-like states. Wildtype and transgenic flies were subjected to various conditions prior to behavioural testing. The results indicate that wall-following and total walking activity are independent measures that are modulated, with generally increased wall-following observed under aversive stimuli and decreased values under positive conditions, independent of the time of day. The effects of genetic manipulation of selected neuromodulatory systems support their role in modulating emotion-like states in Drosophila . Activation of reward-related neurons decreased wall-following while inhibition increased it. Moreover, treatment with ethanol or diazepam produced predictable changes in behaviour. Our findings suggest that Drosophila shares conserved core emotion-like building blocks with vertebrates, and show that wall-following and total walking activity in the OFT can serve as a reliable indicator of emotional valence and arousal in the fruit fly. This positions Drosophila as a powerful genetic model to dissect the neuronal and neurochemical substrates of emotion primitives.
Lymphatic vessels beat faster as they fill with fluid through a chain of calcium signaling, though the first pressure sensor remains a mystery.
