bioRxiv

Journal: bioRxiv

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Cold Spring Harbor Laboratory

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Publications 1 - 10 of 330

The role of memory and perspective shifts in systematic biases during object location estimation
Segen, Vladislava; Colombo, Giorgio; Avraamides, Marios; et al. (2021)
bioRxiv
Our previous research highlighted a systematic bias in a spatial memory task, with participants correctly detecting object movements in the same direction as the perspective shift, whilst misjudging the direction of object movements if those were in the opposite direction to the perspective shift. The aim of the current study was to investigate if the introduction of perspective shifts results in systematic biases in object location estimations. To do so, we asked participants to encode the position of an object in a virtual room and to then estimate the object’s position following a perspective shift. In addition, by manipulating memory load (perception and memory condition) we investigated if the bias in object position estimates results from systematic distortions introduced in spatial memory. Overall, our results show that participants make systematic errors in estimating object positions in the same direction as the perspective shift. This bias was present in both the memory and the perception condition. We propose that the systematic bias in the same direction as the perspective shift is driven by difficulties in understanding the perspective shifts that may lead participants to use an egocentric representation of object positions as an anchor when estimating the object location following a perspective shift, thereby giving rise to a systematic shift in errors in the same direction as the perspective shift.
A modular chemigenetic calcium indicator enables in vivo functional imaging with near-infrared light
Farrants, Helen; Shuai, Yichun; Lemon, William C.; et al. (2023)
bioRxiv
Genetically encoded fluorescent calcium indicators have revolutionized neuroscience and other biological fields by allowing cellular-resolution recording of physiology during behavior. However, we currently lack bright, genetically targetable indicators in the near infrared that can be used in animals. Here, we describe WHaloCaMP, a modular chemigenetic calcium indicator built from bright dye-ligands and protein sensor domains that can be genetically targeted to specific cell populations. Fluorescence change in WHaloCaMP results from reversible quenching of the bound dye via a strategically placed tryptophan. WHaloCaMP is compatible with rhodamine dye-ligands that fluoresce from green to near-infrared, including several dye-ligands that efficiently label the central nervous system in animals. When bound to a near-infrared dye-ligand, WHaloCaMP1a is more than twice as bright as jGCaMP8s, and shows a 7× increase in fluorescence intensity and a 2.1 ns increase in fluorescence lifetime upon calcium binding. We use WHaloCaMP1a with near-infrared fluorescence emission to image Ca2+ responses in flies and mice, to perform three-color multiplexed functional imaging of hundreds of neurons and astrocytes in zebrafish larvae, and to quantitate calcium concentration using fluorescence lifetime imaging microscopy (FLIM).
Positive interactions support complex networks
Losapio, Gianalberto; De la Cruz, Marcelino; Escudero, Adrian; et al. (2017)
bioRxiv
A Bayesian Nonparametric Approach to Discover Clinico-Genetic Associations across Cancer Types
Pradier, Melanie F.; Hyland, Stephanie L.; Stark, Stefan G.; et al. (2019)
bioRxiv
Motivation Personalized medicine aims at combining genetic, clinical, and environmental data to improve medical diagnosis and disease treatment, tailored to each patient. This paper presents a Bayesian nonparametric (BNP) approach to identify genetic associations with clinical/environmental features in cancer. We propose an unsupervised approach to generate data-driven hypotheses and bring potentially novel insights about cancer biology. Our model combines somatic mutation information at gene-level with features extracted from the Electronic Health Record. We propose a hierarchical approach, the hierarchical Poisson factor analysis (H-PFA) model, to share information across patients having different types of cancer. To discover statistically significant associations, we combine Bayesian modeling with bootstrapping techniques and correct for multiple hypothesis testing. Results Using our approach, we empirically demonstrate that we can recover well-known associations in cancer literature. We compare the results of H-PFA with two other classical methods in the field: case-control (CC) setups, and linear mixed models (LMMs).
Transcriptome and epigenome characterization of mouse spermatogonial cells reveals distinct chromatin regulatory landscapes in postnatal and adult testis
Lazar-Contes, Irina; Tanwar, Deepak K.; Germain, Pierre-Luc; et al. (2020)
bioRxiv
The distribution of plasmid fitness effects explains plasmid persistence in bacterial communities
Alonso-del Valle, Aida; Leon-Sampedro, Ricardo; Rodríguez-Beltrán, Jerónimo; et al. (2020)
bioRxiv
Plasmid persistence in bacterial populations is strongly influenced by the fitness effects associated with plasmid carriage. However, plasmid fitness effects in wild-type bacterial hosts remain largely unexplored. In this study, we determined the distribution of fitness effects (DFE) for the major antibiotic resistance plasmid pOXA-48 in wild-type, ecologically compatible enterobacterial isolates from the human gut microbiota. Our results show that although pOXA-48 produced an overall reduction in bacterial fitness, the DFE was dominated by quasi-neutral effects, and beneficial effects were observed in several isolates. Incorporating these data into a simple population dynamics model revealed a new set of conditions for plasmid stability in bacterial communities, with plasmid persistence increasing with bacterial diversity and becoming less dependent on conjugation. Moreover, genomic results showed a link between plasmid fitness effects and bacterial phylogeny, helping to explain pOXA-48 epidemiology. Our results provide a simple and general explanation for plasmid persistence in natural bacterial communities.
Extracellular matrix gene expression signatures as cell type and cell state identifiers
Sacher, Fabio; Feregrino, Christian; Tschopp, Patrick; et al. (2021)
bioRxiv
Transcriptomic signatures based on cellular mRNA expression profiles can be used to categorize cell types and states. Yet whether different functional groups of genes perform better or worse in this process remains largely unexplored. Here we test the core matrisome - that is, all genes coding for structural proteins of the extracellular matrix - for its ability to delineate distinct cell types in embryonic single-cell RNA-sequencing (scRNA-seq) data. We show that even though expressed core matrisome genes correspond to less than 2% of an entire cellular transcriptome, their RNA expression levels suffice to recapitulate important aspects of cell type-specific clustering. Notably, using scRNA-seq data from the embryonic limb, we demonstrate that core matrisome gene expression outperforms random gene subsets of similar sizes and can match and exceed the predictive power of transcription factors. While transcription factor signatures generally perform better in predicting cell types at early stages of chicken and mouse limb development, i.e., when cells are less differentiated, the information content of the core matrisome signature increases in more differentiated cells. Our findings suggest that each cell type produces its own unique extracellular matrix, or matreotype, which becomes progressively more refined and cell type-specific as embryonic tissues mature.
Goal-directed vocal planning in a songbird
Zai, Anja T.; Stepien, Anna E.; Cavé-Lopez, Sophie; et al. (2022)
bioRxiv
Songbirds’ vocal mastery is impressive, but to what extent is it a result of practice? Can they, similar to humans, plan targeted changes to their songs in a practice-free manner without intermittently singing? In adult zebra finches, we drive the pitch of a song syllable away from its stable (baseline) variant acquired from a tutor, then we withdraw reinforcement and subsequently deprive them of song experience by muting or deafening. In this deprived state, birds do not recover their baseline song. However, they revert their songs towards the target by about one standard deviation of their recent practice, provided the latter signaled a pitch mismatch with the target. Thus, targeted vocal plasticity does not require immediate sensory experience, showing that zebra finches are capable of goal-directed vocal planning.
B cell clonal expansion is correlated with antigen-specificity in young but not old mice
Agrafiotis, Andreas; Neumeier, Daniel; Hong, Kai-Lin; et al. (2021)
bioRxiv
Aging of the humoral immune response has been shown to affect its critical role in defending the host from a variety of pathogens. Technical limitations have nevertheless made it challenging to investigate the relationship between genotype and phenotype of antibody repertoires in the context of aging. We therefore performed single-cell sequencing of over 95,000 B cells to simultaneously investigate B cell receptor (BCR) repertoires and gene expression profiles in the bone marrow and spleens of young and old mice following immunizations with a protein antigen. We discovered the presence of clonally expanded B cells in both young and old mice, which had distinct transcriptional phenotypes and exhibited age-associated gene signatures relating to plasma cell differentiation and protein folding and stabilization genes. Recombinant expression of 227 monoclonal antibodies revealed that clonally expanded B cells were frequently antigen-specific in young mice but not in old mice. Furthermore, we detected clonal convergence across different mice which was correlated with antigen-specificity. Although isotype- and expansion-specific transcriptional phenotypes could be detected, there was little correlation with antigen-specificity and transcriptional signatures. Together, our work provides an age-resolved single-cell repertoire resource that further relates antibody specificity, repertoire features, and whole transcriptomes.
Higher seed yield through selection for reduced seed shattering in Italian ryegrass (Lolium multiflorum Lam.)
Kiesbauer, Jenny; Kölliker, Roland; Hug, Maria; et al. (2023)
bioRxiv
Seed shattering, i.e., the loss of seeds at ripening stage shortly before or during seed harvest, is strongly reducing seed yield in Italian ryegrass (Lolium multiflorum Lam.). The aim of this study was to evaluate the possibility to reduce seed shattering within breeding germplasm via recurrent phenotypic selection on spaced plants. Starting from a founder population of 300 plants serving as F0 population, two cycles of phenotypic selection for high and low seed shattering were applied and compared to randomly selected individuals on spaced plant level and in plot trials. Comparison of the five resulting populations in a spaced plant trial revealed a significant effect of selection, with lowest seed shattering (15.3%) observed in the population selected twice for decreased shattering (15.3%) and highest seed shattering (47.9%) for the population selected twice for increased shattering. The same ranking of the five F2 populations was observed in a subsequent trial with sown plots. Thus, using the method presented here, recurrent selection on single spaced plants allows to efficiently reduce seed shattering and, therefore, to increase seed yield in swards.

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Journal: bioRxiv

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