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Forster, S.

Publications and source records attributed to Forster, S..

3 recordsLinked to original sources

Sensory representations in primary visual cortex are not sufficient for subjective imagery

The contemporary definition of mental imagery is characterized by two aspects: a sensory representation resembling, but not resulting from, perception, and an associated subjective experience. Neuroimaging demonstrated imagery-related sensory representations in primary visual cortex (V1) that show striking parallels to perception. However, it remains unclear whether these representations always reflect subjective experience, or they can be dissociated from it. We addressed this question by comparing sensory representations and subjective imagery among visualizers and aphantasics, the latter with an impaired ability to experience imagery. Importantly, to test for the presence of sensory representations independently of the ability to generate imagery on demand we examined both spontaneous and voluntary imagery forms. Using multivariate fMRI, we tested for decodable sensory representations in V1 and subjective visual imagery reports that occurred either spontaneously (during passive listening of evocative sounds) or in response to the instruction to voluntarily generate imagery of the sound content (always while blindfolded inside the scanner). Among aphantasics, V1 decoding of sound content was at chance during voluntary imagery, and lower than in visualizers, but it succeeded during passive listening, despite them reporting no imagery. In contrast, in visualizers, decoding accuracy in V1 was greater in voluntary than spontaneous imagery (while being positively associated with the reported vividness of both imagery types). Finally, for both conditions, decoding in precuneus was successful in visualizers but at chance for aphantasics. Together, our findings show that V1 representations can be dissociated from subjective imagery, while implicating a key role of precuneus in the latter.

neuroscience↗

Development of safe and effective bacteriophage-mediated therapies against C. difficile infections a proof-of-concept preclinical study

BackgroundFecal microbiota transplantation (FMT) and fecal virome transplantation (FVT, sterile filtrated donor feces) have been effective in treating recurrent Clostridioides difficile infections, possibly through bacteriophage-mediated modulation of the gut microbiome. However, challenges like donor variability, costly screening, coupled with concerns over pathogen transfer (incl. eukaryotic viruses) with FMT or FVT hinders their wider clinical application in treating less acute diseases. MethodsTo overcome these challenges, we developed methods to broaden FVTs clinical application while maintaining efficacy and increasing safety. Specifically, we employed the following approaches: 1) Chemostat-fermentation to reproduce the bacteriophage FVT donor component and remove eukaryotic viruses (FVT-ChP), 2) solvent-detergent treatment to inactivate enveloped viruses (FVT-SDT), and 3) pyronin-Y treatment to inhibit RNA-virus replication (FVT-PyT). We assessed the efficacy of these processed FVTs in a C. difficile infection mouse model and compared them with untreated FVT (FVT-UnT), FMT, and saline. ResultsFVT-SDT, FVT-UnT, and FVT-ChP reduced the incidence of mice reaching the humane endpoint (0/8, 2/7, and 3/8, respectively) compared to the FMT, FVT-PyT, and saline control (5/8, 7/8, and 5/7, respectively) and significantly reduced the load of colonizing C. difficile cells and toxin A/B levels. There was a potential elimination of C. difficile colonization, with 7 out of 8 mice treated with FVT-SDT testing negative with qPCR. In contrast, all other treatments exhibited the continued presence of C. difficile. Moreover, the results were supported by changes in the gut microbiome profiles, cecal cytokine levels and histopathological findings. Assessment of viral engraftment following FMT/FVT treatment and host-phage correlations analysis suggested that transfer of phages likely were an important contributing factor associated with treatment efficacy. ConclusionsThis proof-of-concept study show that specific modifications to FVT hold promise in addressing challenges related to donor variability and infection risks. Two strategies lead to treatments significantly limiting C. difficile colonization in mice, with solvent/detergent treatment and chemostat-propagation emerging as promising approaches.

microbiology↗

Multi-hallmark long noncoding RNA maps reveal non-small cell lung cancer vulnerabilities

Long noncoding RNAs (lncRNAs) are widely dysregulated in cancer, yet their functional roles in cellular disease hallmarks remain unclear. Here we employ pooled CRISPR deletion to perturb all 831 lncRNAs in KRAS-mutant non-small cell lung cancer (NSCLC), and measure their contribution to proliferation, chemoresistance and migration across two cell backgrounds. Integrative analysis of this data outperforms conventional "dropout" screens in identifying cancer genes, while prioritising disease-relevant lncRNAs with pleiotropic and background-independent roles. Altogether 60 high-confidence oncogenic lncRNAs are active in NSCLC, the majority identified here for the first time, and which tend to be amplified and overexpressed in tumours. A follow-up antisense oligonucleotide (ASO) screen shortlisted two candidates, Cancer Hallmarks in Lung LncRNA (CHiLL 1&2), whose knockdown consistently suppressed cancer hallmarks in a variety of 2D and 3D tumour models. Molecular phenotyping reveals that CHiLL 1&2 control cellular-level phenotypes via distinct transcriptional networks converging on common oncogenic pathways. In summary, this work reveals a multi-dimensional functional lncRNA landscape underlying NSCLC that contains potential therapeutic vulnerabilities.

genomics↗