Biology subjects

Perlman, M.

Publications and source records attributed to Perlman, M..

4 recordsLinked to original sources

bioRxiv2020

A versatile human intestinal organoid-derived epithelial monolayer model for the study of enteric pathogens

Gastrointestinal infections cause significant morbidity and mortality worldwide. The complexity of human biology and limited insights into host-specific infection mechanisms are key barriers to current therapeutic development. Here, we demonstrate that two-dimensional epithelial monolayers derived from human intestinal organoids, combined with in vivo-like bacterial culturing conditions, provide significant advancements for the study of enteropathogens. Monolayers from the terminal ileum, cecum, and ascending colon recapitulated the composition of the gastrointestinal epithelium, in which several techniques were used to detect the presence of enterocytes, mucus-producing goblet cells, and other cell types following differentiation. Importantly, the addition of receptor activator of nuclear factor kappa-B ligand (RANKL) increased the presence of M cells, critical antigen-sampling cells often exploited by enteric pathogens. For infections, bacteria were grown under in vivo-like conditions known to induce virulence. Overall, interesting patterns of tissue tropism and clinical manifestations were observed. Shigella flexneri adhered efficiently to the cecum and colon; however, invasion in the colon was best following RANKL treatment. Both Salmonella Typhi and Typhimurium serovars displayed different infection patterns, with S. Typhimurium causing more destruction of the terminal ileum and S. Typhi infecting the cecum more efficiently than the ileum, particularly with regards to adherence. Finally, various pathovars of Escherichia coli validated the model by confirming only adherence was observed with these strains. This work demonstrates that the combination of human-derived tissue with targeted bacterial growth conditions enables powerful analyses of human-specific infections that could lead to important insights into pathogenesis and accelerate future vaccine development. ImportanceWhile traditional laboratory techniques and animal models have provided valuable knowledge in discerning virulence mechanisms of enteric pathogens, the complexity of the human gastrointestinal tract has hindered our understanding of physiologically relevant, human-specific interactions; and thus, has significantly delayed successful vaccine development. The human intestinal organoid-derived epithelial monolayer (HIODEM) model closely recapitulates the diverse cell populations of the intestine, allowing for the study of human-specific infections. Differentiation conditions permit the expansion of various cell populations, including M cells that are vital to immune recognition and the establishment of infection by some bacteria. We provide details of reproducible culture methods and infection conditions for the analyses of Shigella, Salmonella, and pathogenic Escherichia coli in which tissue tropism and pathogen-specific infection patterns were detected. This system will be vital for future studies that explore infection conditions, health status, or epigenetic differences; and will serve as a novel screening platform for therapeutic development.

microbiology↗

bioRxiv2020

4DNvestigator: a toolbox for the analysis of time series Hi-C and RNA-seq data

Data on genome organization and output over time, or the 4D Nucleome (4DN), require synthesis for meaningful interpretation. Development of tools for the efficient integration of these data is needed, especially for the time dimension. We present the "4DNvestigator", a user-friendly network based toolbox for the analysis of time series genome-wide genome structure (Hi-C) and gene expression (RNA-seq) data. Additionally, we provide methods to quantify network entropy, tensor entropy, and statistically significant changes in time series Hi-C data at different genomic scales. Availabilityhttps://github.com/lindsly/4DNvestigator

bioinformatics↗

bioRxiv2017

The emergence of words from vocal imitations

People have long pondered the evolution of language and the origin of words. Here, we investigate how conventional spoken words might emerge from imitations of environmental sounds. Does the repeated imitation of an environmental sound gradually give rise to more word-like forms? In what ways do these forms resemble the original sounds that motivated them (i.e., exhibit iconicity)? Participants played a version of the childrens game \"Telephone\". The first generation of participants imitated recognizable environmental sounds (e.g., glass breaking, water splashing). Subsequent generations imitated the previous generation of imitations for a maximum of 8 generations. The results showed that the imitations became more stable and word-like, and later imitations were easier to learn as category labels. At the same time, even after 8 generations, both spoken imitations and their written transcriptions could be matched above chance to the category of environmental sound that motivated them. These results show how repeated imitation can create progressively more word-like forms while continuing to retain a resemblance to the original sound that motivated them, and speak to the possible role of human vocal imitation in explaining the origins of at least some spoken words.

evolutionary biology↗

bioRxiv2017

The Potential for Iconicity in Vocalization

The innovation of iconic gestures is essential to establishing the symbolic vocabularies of signed languages, but might iconicity also play a role in the origin of various spoken words? Can people create novel vocalizations that are comprehensible to naive listeners without the use of prior conventions? To test this capacity, we launched a contest in which participants submitted a set of non-linguistic vocalizations for 30 meanings spanning actions, humans, animals, inanimate objects, properties, quantifiers and demonstratives. The winner - who received a monetary prize - was judged by the ability of naive listeners to successfully infer the meanings of the vocalizations. We report the results from the contest, along with a series of experiments and analyses designed to evaluate the vocalizations for: 1) their comprehensibility to naive listeners; 2) the degree to which they resembled their meanings, i.e., were iconic; 3) agreement between producers and listeners in what constitutes an iconic vocalization; and 4) whether iconicity helps naive listeners learn the vocalizations as category labels. The results show that contestants were able to create iconic vocalizations for a wide array of semantic domains, and that these vocalizations were largely comprehensible to naive listeners, as well as easier to learn as category labels. These findings provide a compelling demonstration of the extent to which iconic vocalizations can enable interlocutors to establish understanding through vocalizations in the absence of conventions. This suggests the possibility that, prior to the advent of full-blown spoken languages, people could have used iconic vocalizations to ground a spoken vocabulary with considerable semantic breadth.

animal behavior and cognition↗