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Biology subjects

Shin, I.

Publications and source records attributed to Shin, I..

3 recordsLinked to original sources

A neural circuit for stereopsis in the fly

Stereopsis involves combining different views from the two eyes to infer depth, an ability that has intrigued neuroscientists for almost two centuries (Wheatstone, 1838). It enables insects such as the praying mantis to estimate the distance of prey (Nityananda et al., 2018), or primates to fixate objects at different depths (Cumming and Judge, 1986; Rashbass and Westheimer, 1961). While theoretical models for stereopsis have been proposed based on neural activity recordings (Marr and Poggio, 1976; Grossberg, 1983; Ohzawa et al., 1990), we do not have a detailed circuit mechanism for stereopsis founded on neural wiring. Here we achieve this in the fly, Drosophila melanogaster, by analyzing two whole-brain connectomes (Dorkenwald et al., 2024; Berg et al., 2026). Flies have sufficient overlap between the eyes to utilize binocular vision (Kemppainen et al., 2022); however, a circuit that performs stereopsis has not been uncovered in this model system. We show that a cell type that connects the two optic lobes called LC14 (Otsuna and Ito, 2006) forms a recurrent circuit across the brain that is capable of depth estimation. By building a connectome-constrained model, we demonstrate that recurrence is critical for binocular distance tuning in this circuit. Tuning is optimal for the size and distances of social targets (other flies), and we uncover a pathway within the brain specific for binocular vision computations. Silencing LC14 neurons renders this downstream circuitry sensitive to only monocular information and alters distance-dependent courtship behaviors, while activation of LC14 neurons causes flies to slow in response to an illusory object in their binocular visual field. In sum, we predict function from structure, uncovering how the fly brain computes distance from binocular cues, and identify a role for binocular vision in patterning social behavior.

neuroscience↗

Genomic hypomethylation in cell-free DNA predicts responses to checkpoint blockade in lung and breast cancer

Genomic hypomethylation has recently been identified as a determinant of therapeutic responses to immune checkpoint blockade (ICB). However, tumor tissue is often unattainable, and tissue-based methylation profiling suffers from low tumor purity. In this study, we developed an assay named iMethyl to estimate the genomic hypomethylation status from cell-free DNA (cfDNA) as well as tissue by deep targeted sequencing of young LINE-1 elements with > 400,000 reads per sample. iMethyl was applied to a total of 653 ICB samples encompassing lung cancer (cfDNA n=167; tissue n=137; cfDNA early during treatment n=40), breast cancer (cfDNA n=91; tissue n=50; PBMC n=50; cfDNA at progression n=44), and ovarian cancer (tissue n=74). iMethyl-tissue had better predictive power than tumor mutation burden and PD-L1 expression. Furthermore, iMethyl-liquid predicted ICB responses accurately regardless of the tumor purity of tissue samples. iMethyl-liquid was also able to monitor therapeutic responses early during treatment (3 or 6 weeks after initiation of ICB) and detect progressive hypomethylation accompanying tumor progression. In conclusion, our method allows for reliable noninvasive prediction, early evaluation, and monitoring of clinical responses to ICB therapy.

cancer biology↗

Human Saliva Modifies Growth, Biofilm Architecture and Competitive Behaviors of Oral Streptococci

The bacteria within supragingival biofilms participate in complex exchanges with other microbes inhabiting the same niche. One example are the mutans group streptococci (Streptococcus mutans), implicated in the development of tooth decay, and other health-associated commensal streptococci species. Previously, our group transcriptomically characterized intermicrobial interactions between S. mutans and several species of oral bacteria. However, these experiments were carried out in a medium that was absent of human saliva. To better mimic their natural environment, we first evaluated how inclusion of saliva affected growth and biofilm formation of eight streptococci species individually, and found saliva to positively benefit growth rates while negatively influencing biomass accumulation and altering spatial arrangement. These results carried over during evaluation of 29 saliva-derived isolates of various species. Surprisingly, we also found that addition of saliva increased the competitive behaviors of S. mutans in coculture competitions against commensal streptococci that led to increases in biofilm microcolony volumes. Through transcriptomically characterizing mono- and cocultures of S. mutans and Streptococcus oralis with and without saliva, we determined that each species developed a nutritional niche under mixed-species growth, with S. mutans upregulating carbohydrate uptake and utilization pathways while S. oralis upregulated genome features related to peptide uptake and glycan foraging. S. mutans also upregulated genes involved in oxidative stress tolerance, particularly manganese uptake, which we could artificially manipulate by supplementing in manganese to give it an advantage over its opponent. Our report highlights observable changes in microbial behaviors via leveraging environmental- and host-supplied resources over their competitors.

microbiology↗