Biology subjects

Tan, H. Y.

Publications and source records attributed to Tan, H. Y..

6 recordsLinked to original sources

bioRxiv2025

Sourdough starter-inspired living materials grown from probiotic consortia with engineered division-of-labor

Genetic circuits enable precise control over cellular behavior. As circuits become more complex, implementing them within a single cell population becomes difficult. Tasks can instead be distributed in engineered consortia. However, selecting appropriate consortia and harnessing the natural traits of each species for such a division of labor remain unsolved challenges. Here, we report the creation of SINERGY, an engineered synthetic sourdough starter in which functional modules are distributed between the two constituent species. These modules, consisting of sensing, communication, and response, enable in vitro biosensing and in vivo drug delivery and modulate the gut ecosystem in an animal disease model. SINERGY not only preserves the safety and health-promoting properties of the natural components but also endows microbes with programmable functionalities, facilitating broad applications in biomedicine.

synthetic biology↗

bioRxiv2024

Causal Discovery Analysis Reveals Insights into Psychosis Proneness, Brain Function, and Environmental Factors among Young Individuals

BackgroundExperiencing symptoms of psychosis, such as delusions and hallucinations, are observed in general, nonclinical populations. These experiences are sometimes described as psychosis proneness (PP) and potentially part of the psychosis continuum. The directional relationships among various factors contributing to psychosis proneness and its interactions, encompassing both environmental and neural mechanisms, lack comprehensive description. We aimed to identify targets to prevent psychosis proneness and its interactions by characterizing pathways using causal discovery analysis (CDA). MethodsParticipants were 194 healthy adolescent and young adult twin and sibling pairs aged between 14-24 years from Turkiye. They completed comprehensive assessments evaluating sociodemographic status, environmental risk, general intelligence, self-schema, PP, and working memory (WM) performance during fMRI (37 variables). CDA was applied, a novel machine learning algorithm, to understand the causal relationships of PP. ResultsThe analysis identified negative self-schema as having the largest causal effect among all assessments in PP [Effect size (ES)= 0.55]. Secondly, social cohesion and trust (SC&T) had a protective causal effect on PP [ES= -0.18]. Lastly, PP was identified as a direct cause of greater activation in DLPFC (BA9a-BA46v) during manipulation in the WM (ES= 0.14). ConclusionsCDA provides directionality of the 37 variables which were not presented earlier. The findings highlight the significance of negative self-schema and SC&T in the general population with PP, emphasizing the potential for preventive interventions targeting these factors. These findings also suggest a role for DLPFC as a potential target in this regard. To our knowledge, this is the first study using data-driven analysis to model causal mechanisms in PP in the general population.

neuroscience↗

bioRxiv2021

Biomimetic Vasculatures by 3D-Printed Porous Molds

Anatomically and biologically relevant vascular models are critical to progress our understanding of cardiovascular diseases (CVDs) that can lead to effective therapies. Despite advances in 3D bioprinting, recapitulating complex architectures (i.e., freestanding, branching, multilayered, perfusable) of a cell-laden vascular construct remains technically challenging, and the development of new techniques that can recapitulate both anatomical and biological features of blood vessels is of paramount importance. In this work, we introduce a unique, microfluidics-enabled molding technique that allows us to fabricate anatomically-relevant, cell-laden hydrogel vascular models. Our approach employed 3D-printed porous molds of poly(ethylene glycol) diacrylate (PEGDA) as templates to cast alginate-containing bioinks. Due to the porous and aqueous nature of the PEGDA mold, the calcium ion (Ca2+) was diffusively released to crosslink the bioinks to create hollow structures. Applying this technique, multiscale, multilayered vascular constructs that were freestanding and perfusable were readily fabricated using cell-compatible bioinks (i.e., alginate and gelatin methacryloyl (GelMA)). The bioinks were also readily customizable to either improve the compatibility with specific vascular cells or tune the mechanical modulus to mimic native blood vessels. Importantly, we successfully integrated smooth muscle cells and endothelial cells in a biomimetic organization within our vessel constructs and demonstrated a significant increase in monocyte adhesion upon stimulation with an inflammatory cytokine, tumor necrosis factor-alpha (TNF-). We also demonstrated that the fabricated vessels were amenable for testing percutaneous coronary interventions (i.e., drug-eluting balloons and stents) under physiologically-relevant mechanical states, such as vessel stretching and bending. Overall, we introduce a versatile fabrication technique with multi-faceted possibilities of generating biomimetic vascular models that can benefit future research in mechanistic understanding of CVD progression and the development of therapeutic interventions.

bioengineering↗

bioRxiv2019

Parietal prefrontal feedforward connectivity in association with schizophrenia genetic risk and delusions

BackgroundConceptualizations of delusion formation implicate, in part, deficits at feed-forward information transfer across posterior to prefrontal cortices, resulting in dysfunctional integration of new information in favor of over-familiar prior beliefs. Here, we used functional MRI and machine learning models to examine feedforward parietal-prefrontal information transfer in schizophrenia patients in relation to delusional thinking, and polygenic risk for schizophrenia.\n\nMethodsWe studied 66 schizophrenia patients and 143 healthy controls as they performed context updating during working memory (WM). Dynamic causal models of effective connectivity were focused on prefrontal and parietal cortex, where we examined parietal-prefrontal connectivity in relation to delusions in patients. We further tested for an effect of polygenic risk for schizophrenia on connectivity in healthy individuals. We then leveraged support vector regression models to define optimal normalized target connectivity tailored for each patient, and tested the extent to which deviation from this target predicted individual variation in delusion severity.\n\nResultsIn schizophrenia patients, updating and manipulating context information was disproportionately less accurate than was WM maintenance, with a task accuracy-by-diagnosis interaction. Also, patients with delusions tended to have relatively reduced feedforward effective connectivity during context updating in WM manipulation. The same parietal-prefrontal feedforward prefrontal effective connectivity was adversely influenced by polygenic risk for schizophrenia in healthy subjects. Individual patients deviation from predicted normal feedforward connectivity based on the support vector models correlated with delusional severity.\n\nConclusionsThese computationally-derived observations support a role for feed-forward parietal-prefrontal information processing deficits in delusional psychopathology, and in genetic risk for schizophrenia.

neuroscience↗

bioRxiv2019

Dysfunctional and compensatory brain networks underlying math fluency

Poor math fluency, or timed calculation (TC) performance, is a characteristic of dyscalculia, a common cause of poor educational and occupational outcomes. Here, we examined neural substrates of dysfunctional math fluency and potential compensatory mechanisms. We performed functional MRI scans of participants with divergent performance on an event-related TC paradigm (poor TC, <0.5 accuracy, n=34; vs. controls, accuracy>0.8, n=34). Individuals with poor TC had decreased intraparietal sulcus (IPS) engagement, and decreased IPS-striatal and IPS-prefrontal effective connectivity. We next examined an independent well-performing sample (TC accuracy>0.8, n=100), stratified according to relatively low-versus high-IPS activation during TC. Relatively reduced IPS engagement, or patterns of IPS-related effective connectivity similar to those with poor TC, appeared to be compensated for by increased engagement of effective connectivity involving fusiform gyrus, angular gyrus, inferior frontal gyrus and striatum. Neural connectivity involving high-level visual processing in fusiform gyrus and related ventral cortical networks may be relevant in compensatory function ameliorating aspects of dyscalculia and mathematical difficulty.

neuroscience↗

bioRxiv2018

Structural and functional influences of urban and rural childhoods on the medial prefrontal cortex

Global increases in urbanization have brought dramatic economic, environmental and social changes. However, less is understood about how these may influence disease-related brain mechanisms underlying epidemiological observations that urban birth and childhoods may increase the risk for neuropsychiatric disorders, including increased social stress and depression. In a genetically homogeneous Han Chinese adult population with divergent urban and rural birth and childhoods, we examined the structural and functional MRI neural correlates of childhood urbanicity, focusing on behavioral traits responding to social status threats, and polygenic risk for depression. Subjects with divergent rural and urban childhoods were similar in adult socioeconomic status and were genetically homogeneous. Urban childhoods, however, were associated with higher trait anxiety-depression. On structural MRI, urban childhoods were associated with relatively reduced medial prefrontal gray matter volumes. Functional medial prefrontal engagement under social status threat during working memory correlated with trait anxiety-depression in subjects with urban childhoods, to a significantly greater extent than in their rural counterparts, implicating an exaggerated physiological response to the threat context. Stress-associated medial prefrontal engagement also interacted with polygenic risk for depression, significantly predicting a differential response in individuals with urban but not rural childhoods. Developmental urbanicity thus differentially influenced medial prefrontal structure and function, at least in part through mechanisms associated with the neural processing of social status threat, trait anxiety, and genetic risk for depression, which may be factors in the association of urbanicity with adult psychopathology.\n\nSignificance StatementUrban living has been associated with social inequalities and stress. However, less is understood about the neural underpinnings by which these stressors affect disease risk, and in particular, genetic risk for depression. Leveraging urbanization in China, we studied adults with diverse urban and rural upbringings, who were genetically homogeneous and with similar current socioeconomic status, to isolate the effects of childhood urbanicity. At medial prefrontal cortex, a region critical for processing emotional stressors and social status, genetic risk for depression resulted in more deleterious function under stress in individuals with urban, but not rural childhoods. This implicates medial prefrontal cortexs critical role in brain development, integrating genetic mechanisms of stress and depression with the childhood environment.

neuroscience↗