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van der Burg, E.

Publications and source records attributed to van der Burg, E..

3 recordsLinked to original sources

Reciprocal roles of crowding and serial dependence on visual perception

Visual perception arises from the interplay between current and prior sensory inputs. Two perceptual phenomena-serial dependence and visual crowding-result from the mandatory integration of retinal information across time and space, respectively. This study investigated, for the first time, their functional relationship for orientation and brightness discrimination tasks. Participants performed orientation and brightness discrimination tasks (blocked) on peripheral targets surrounded by distractors of varying color, orientation, and proximity. Both serial dependence (the influence of prior stimuli on current judgments) and visual crowding (impaired peripheral recognition caused by nearby distractors) were observed. Similar double dissociations in task and stimulus specificity emerged for both phenomena, suggesting functional links mediated by distinct processing mechanisms for brightness and orientation judgments. Additionally, the two effects interacted: crowding reduced serial dependence on subsequent trials, indicating that spatial information is prioritized over temporal information when spatial redundancy is high. Conversely, serial dependence increased crowding for orientation judgments, while for brightness judgments, serial dependence operated additively without affecting crowding. These interactions were spatially specific, occurring only when targets appeared in the same location across consecutive trials. Notably, a positive correlation between crowding and serial dependence was found exclusively for orientation judgments and only when targets appeared at the same location across trials. The reciprocal interaction and positive correlation between serial dependence and crowding observed for orientation judgments indicate that that these processes are intrinsically linked, possibly via a common neural mechanism. In contrast, for brightness judgments, the unilateral effect of crowding on serial dependence--along with the absence of correlation-indicates distinct neural mechanisms. Here, brightness crowding likely precedes serial dependence, reflecting a prioritization of spatial redundancy minimization over temporal stabilization. These findings suggest that the brain strategically integrates spatial and temporal information through distinct yet overlapping mechanisms, balancing spatial precision with temporal stability based on task demands and stimulus characteristics.

neuroscience↗

CD26-negative and CD26-positive tissue-resident fibroblasts contribute to functionally distinct CAF subpopulations in breast cancer

Cancer-associated fibroblasts (CAFs) are abundantly present in the microenvironment of virtually all tumors and strongly impact tumor progression. Despite increasing insight into their function and heterogeneity, little is known regarding the origin of CAFs. Understanding the origin of CAF heterogeneity is needed to develop successful CAF-based targeted therapies. Through various transplantation studies in mice we determined that CAFs in both invasive lobular breast cancer and triple negative breast cancer originate from mammary tissue-resident normal fibroblasts (NFs). Single-cell transcriptomics, in vivo tracing and in vitro studies revealed the transition of CD26+ and CD26- NF populations into inflammatory CAFs (iCAFs) and myofibroblastic CAFs (myCAFs), respectively. In vitro functional assays showed that CD26+ NFs transition into pro-tumorigenic iCAFs which recruit myeloid cells in a CXCL12-dependent manner and enhance tumor cell invasion via matrix-metalloproteinase (MMP) activity. Together, our data show that CD26+ and CD26- NFs transform into distinct CAF subpopulations in breast cancer.

cancer biology↗

MYC promotes immune-suppression in TNBC via inhibition of IFN signaling

Immune checkpoint inhibitor (ICI) treatment has thus far shown limited efficacy in triple-negative breast cancer (TNBC) patients, presumably due to sparse or unresponsive tumor-infiltrating lymphocytes. We reveal a strong correlation between MYC expression and loss of immune signatures in human TNBC. In mouse models of BRCA1-proficient and -deficient TNBC, MYC overexpression dramatically decreased lymphocyte infiltration in tumors, along with immune signature loss. Likewise, MYC overexpression suppressed inflammatory signaling induced by BRCA1/2 inactivation in human TNBC cell lines. Moreover, MYC overexpression prevented the recruitment and activation of lymphocytes in co-cultures with human and mouse TNBC models. Chromatin immunoprecipitation (ChIP)-sequencing revealed that MYC directly binds promoters of multiple interferon-signaling genes, which were downregulated upon MYC expression. Finally, MYC overexpression suppressed induction of interferon signaling and tumor growth inhibition by a Stimulator of Interferon Genes (STING) agonist. Together, our data reveal that MYC suppresses innate immunity and facilitates immune escape, explaining the poor immunogenicity of MYC-overexpressing TNBCs. Statement of SignificanceMYC suppresses recruitment and activation of immune cells in TNBC by repressing the transcription of interferon genes. These findings provide a mechanistic rationale for the association of high MYC expression levels with immune exclusion in human TNBCs, which might underlie the relatively poor response of many TNBCs to ICI.

cancer biology↗