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Jovanovic, L.

Publications and source records attributed to Jovanovic, L..

4 recordsLinked to original sources

Passage of time at the level of milliseconds: a new approach and a selective difficulty in individuals with schizophrenia

Background and HypothesisIndividuals with schizophrenia report that to them time sometimes feels discontinuous. Previous work has shown a link between the sense of self, and the ability to prepare to react to a target and to benefit from the passage of time, at the level of a few hundreds of milliseconds. However, the sense of time continuity requires a higher time resolution than examined in previous studies. Here we investigate to which extent individuals with schizophrenia and controls benefit from an increased delay when detecting asynchronies in the order of tens of milliseconds (stimulus onset asynchronies, i.e. SOA) between two successive visual stimuli. Study DesignWe re-analyzed three datasets and contrasted performance when the SOA increases, remains identical or decreases from trial t-1 to trial t. Study ResultsPerformance of all participants improved with an increase in the SOA, as the task became easier, but for controls more so than individuals with schizophrenia. These results are replicated across datasets, and were specific to the condition when SOA increased from one trial to the next. There was no significant group difference when the SOA decreased or remained identical. This was true even when the latter condition was more frequent, and when SOA magnitude was equalized across the conditions. Importantly, the difference between the two groups was specific to temporal judgements, and was not observed in a control masking task. ConclusionsWe suggest the results reveal a difficulty for individuals with schizophrenia to experience time at the level of milliseconds.

neuroscience↗

Spatial and temporal contexts drive visual temporal integration via spatiotemporal normalisation

The visual system is known to integrate sensory information across both space and time, but these dimensions are often studied separately. Here we provide novel behavioural evidence for an early integration over space and time, and propose a computational model of this integration that is biologically plausible. We designed a controlled task that forces human participants to integrate information over both space and time to perform well. Stimuli were temporally segmented rings of oriented elements and participants had to detect a missing element in the ring. We found that temporal integration was enhanced when successive visual events were temporally proximate, spatially aligned to form a continuous contour, but also, and more surprisingly, when they were brief. Notably, the spatial effects on integration are temporally asymmetric: integration is facilitated when more events are presented earlier in the sequence, and even more so when they form a collinear contour. These findings indicate that temporal integration is sensitive to both the spatial configuration and the number of visual events presented over time, supporting a continuous rather than discrete process at early visual stages. All of these results are well accounted for by a computational model in which temporal integration arises from the overlap of internal signals generated by individual visual events. These signals are shaped by a spatially and temporally tuned divisive normalisation mechanism and integrated via coincidence detection. Predictions from this model match human performance in seminal past work as well as novel stimulus displays, offering an account of how spatio-temporal interactions determine what we perceive and when.

neuroscience↗

Single-Cell RNA Sequencing and Inferred Protein Activity Analysis Reveal a Distinct Tumor Phenotype in Early-Onset Colorectal Cancer Patients

Colorectal cancer (CRC) diagnosed before age 50 years (early-onset CRC, EO-CRC) is rising at an alarming rate, yet its molecular and microenvironmental drivers remain poorly understood. EO-CRC is highly heterogeneous, and while subtle differences from late-onset CRC (LO-CRC) have been reported, their full extent remains unresolved due to the limited scope of previous studies. Here, we integrate public data with in-house clinical samples profiled by single-cell RNA sequencing (scRNA-seq) and multiplex immunofluorescence (mIF) to compare EO-CRC and LO-CRC. Additionally, we employ gene regulatory network-based protein activity inference (VIPER), enabling a more precise characterization of key regulatory proteins driving tumor-stroma interactions. Our analysis reveals that EO-CRC and LO-CRC have a largely similar immune composition, challenging previous reports of an "immune-cold" phenotype in EO-CRC. However, we identify distinct stromal differences, including a significant enrichment of fibroblasts in EO-CRC. Notably, we define a previously unrecognized epithelial subpopulation in EO-CRC, marked by high expression of toll-like receptor 4 (TLR4) and C-C chemokine receptor type 5 (CCR5)--key mediators of inflammation-driven tumor progression and fibroblast recruitment. These findings suggest that EO-CRC may be driven by a tumor-intrinsic inflammatory phenotype with enhanced stromagenesis, providing new insights into potential mechanisms underlying its increasing incidence in young adults.

cancer biology↗

The long non-coding RNA GHSROS reprograms prostate cancer cell lines toward a more aggressive phenotype

It is now appreciated that long non-coding RNAs (lncRNAs) are important players in the orchestration of cancer progression. In this study we characterized GHSROS, a human lncRNA gene on the opposite DNA strand (antisense) to the ghrelin receptor gene, in prostate cancer. The lncRNA was upregulated by prostate tumors from different clinical datasets. Consistently, transcriptome data revealed that GHSROS alters the expression of cancer-associated genes. Functional analyses in vitro showed that GHSROS mediates tumor growth, migration, and survival and resistance to the cytotoxic drug docetaxel. Increased cellular proliferation of GHSROS-overexpressing PC3, DU145, and LNCaP prostate cancer cell lines in vitro was recapitulated in a subcutaneous xenograft model. Conversely, in vitro antisense oligonucleotide inhibition of the lncRNA reciprocally regulated cell growth and migration, and gene expression. Notably, GHSROS modulates the expression of PPP2R2C, the loss of which may drive androgen receptor pathway-independent prostate tumor progression in a subset of prostate cancers. Collectively, our findings suggest that GHSROS can reprogram prostate cancer cells toward a more aggressive phenotype and that this lncRNA may represent a potential therapeutic target.

cancer biology↗