Biology subjects

Kwan, A.

Publications and source records attributed to Kwan, A..

6 recordsLinked to original sources

bioRxiv2026

Photopatterned Sacrificial Vascular Architectures for Large Tissue-Scale Oxygenation

The engineering of thick, metabolically active tissues is constrained by the lack of scalable methods to create perfusable vasculature. This hinders effective metabolite transport in large tissue volumes, posing a critical barrier for regenerative tissue applications. In this study, we introduce photopatterned Channel Architectures with Sacrificial Templates (pCAST), an additive manufacturing strategy for generating three dimensional (3D), interconnected vascular networks with precisely defined negative space. Water-soluble sacrificial templates were fabricated using scalable Continuous Liquid Interface Production (CLIP), embedded within tissue constructs, and flushed away to yield 50 {micro}m perfusable channels spanning centimeter-scale tissue constructs. We then apply experimental oxygen mapping and viability analysis to pCAST constructs to build finite-element models that predict patterns of oxygen availability and tissue survival are governed by the balance between metabolic demand and vascular architecture, consistent with reaction-diffusion theory. This computational framework quantitatively predicts oxygen distributions and viability boundaries across vascular geometries and is validated experimentally. Together, these results establish pCAST as a scalable design framework linking vascular architecture, perfusion, and metabolic support for engineering large, 3D perfused tissue constructs. SignificanceThe ability to engineer thick, living tissues is limited by poor oxygen and nutrient delivery, which causes cell death before tissues can function or integrate with the body. This work addresses that fundamental barrier by introducing photopatterned Channel Architecture with Sacrificial Templates (pCAST), a scalable manufacturing strategy that creates precisely defined, perfusable vascular networks inside 3D tissues. By combining high-resolution 3D printing, sacrificial templating, and quantitative oxygen mapping, this research establishes design rules that link vascular geometry, perfusion, and tissue viability. These insights provide a general framework for building large, metabolically active tissues, with direct relevance to cardiac patches and other regenerative medicine applications.

bioengineering↗

bioRxiv2026

Direct effector recognition by a tandem kinase triggers non-canonical immunity in wheat

Tandem kinase proteins (TKPs) are an important class of disease resistance genes in cereal crops alongside nucleotide-binding (NB-ARC) leucine-rich repeat (LRR) (NLR) receptors. Here, we cloned the wheat (Triticum aestivum) resistance gene Lr41, which encodes a TKP with a C-terminal fusion, and its paired effector gene AvrLr41 from the rust pathogen Puccinia triticina. AvrLr41 is unusually large and highly divergent from most fungal effectors and is directly recognized by Lr41 through its pseudokinase domain. Immune activation mediated by Lr41 require auxiliary helper proteins, including either a minimal coiled-coil (CC) helper protein or its full-length NLR ortholog. These findings reveal a non-canonical immune system in which a kinase-type receptor directly recognizes an effector and recruits either CC or NLR helpers, demonstrating that full-length NLRs are not strictly required for NLR-linked immune execution and expanding the functional repertoire of disease resistance proteins in crops.

plant biology↗

bioRxiv2025

Modulation of Nutritional Composition and Aroma Volatiles in Cultivated Pork Fat by Culture Media Supplementation

Cultivated meat is emerging as a novel food source with the potential to contribute to a more sustainable and ethical food production system. However, limited research to date has explored the extent to which the nutrition and the aroma of such foods can be altered through cell culture conditions. Here, we aimed to modulate the aromatic volatile compounds in heated porcine cultivated fat cells by manipulating the media components while ensuring the preservation of robust fat differentiation. Using dynamic headspace gas chromatography-mass spectrometry (DHS-GC-MS), we demonstrated that supplementing cells with thiamine-HCl increased its intracellular concentration and promoted the production of 4-methyl-5-thiazoleethanol, contributing to milky aroma. Similarly, supplementation with L-methionine enhanced its intracellular concentration and increased the production of methional, a volatile compound with a potato-like aroma. Additionally, myoglobin significantly altered the volatile organic compound profile of cultivated fat. Notably, the concentration of {gamma}-nonalactone, (E,E)-2,4-decadienal and 2-pentylfuran were increased, which contribute to a coconut-like, deep fat, fruity aroma, respectively, as well as elevated levels of other alcohols, aldehydes and furans. These findings highlight the potential of culture media formulations to modulate the aroma in cultivated fat production, a unique opportunity to optimize sensory features using this novel food production technology. HighlightsNutrient composition and aroma profiles of cultivated pork fat upon baking were modulated by cell culture media supplementation. Supplementing with thiamine-HCl, L-methionine, or myoglobin increased intracellular levels of thiamine or methionine and modulated the formation of aroma volatiles, enhancing characteristic odors such as milky, potato-like, and coconut-like notes. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/667495v1_ufig1.gif" ALT="Figure 1"> View larger version (15K): org.highwire.dtl.DTLVardef@11cd7c4org.highwire.dtl.DTLVardef@99b290org.highwire.dtl.DTLVardef@9a47beorg.highwire.dtl.DTLVardef@dc1689_HPS_FORMAT_FIGEXP M_FIG C_FIG Graphical overview of the methodology. Porcine dedifferentiated fat cells (pDFAT) were differentiated into adipocytes using adipogenesis media supplemented with aroma precursors. The cells were heated (cooked) and the resulting volatile compounds were analyzed using dynamic headspace gas chromatography-mass spectrometry (DHS-GC-MS).

biochemistry↗

bioRxiv2024

Long-range neuropeptide relay as a central-peripheral communication mechanism for the context-dependent modulation of interval timing behaviors.

Neuropeptides play crucial roles in regulating context-dependent behaviors, but the underlying mechanisms remain elusive. We investigate the role of the neuropeptide SIFa and its receptor SIFaR in regulating two distinct mating duration behaviors in male Drosophila: Longer-Mating-Duration (LMD) and Shorter-Mating-Duration (SMD). We found that SIFaR expression in specific neurons is required for both LMD and SMD behaviors. Social context and sexual experience lead to synaptic reorganization between SIFa and SIFaR neurons, altering internal states of brain. We revealed that the SIFa-SIFaR/Crz-CrzR neuropeptide relay pathway is essential for generating distinct interval timing behaviors, with Crz neurons being responsive to the activity of SIFa neurons. Additionally, CrzR expression in non-neuronal cells is critical for regulating LMD and SMD behaviors. Our study provides insights into how neuropeptides and their receptors modulate context-dependent behaviors through synaptic plasticity and calcium signaling, with implications for understanding the neural circuitry underlying interval timing and neuropeptidergic system modulation of behavioral adaptations.

neuroscience↗

bioRxiv2020

Single cell resolution regulatory landscape of the mouse kidney highlights cellular differentiation programs and renal disease targets

Determining the epigenetic program that generates unique cell types in the kidney is critical for understanding cell-type heterogeneity during tissue homeostasis and injury response. Here, we profiled open chromatin and gene expression in developing and adult mouse kidneys at single cell resolution. We show critical reliance of gene expression on distal regulatory elements (enhancers). We define key cell type-specific transcription factors and major gene-regulatory circuits for kidney cells. Dynamic chromatin and expression changes during nephron progenitor differentiation demonstrated that podocyte commitment occurs early and is associated with sustained Foxl1 expression. Renal tubule cells followed a more complex differentiation, where Hfn4a was associated with proximal and Tfap2b with distal fate. Mapping single nucleotide variants associated with human kidney disease identified critical cell types, developmental stages, genes, and regulatory mechanisms. We provide a global single cell resolution view of chromatin accessibility of kidney development. The dataset is available via interactive public websites.

developmental biology↗

bioRxiv2019

Polygenic Risk for Skin Autoimmunity Impacts Immune Checkpoint Blockade in Bladder Cancer

PD-1 and PD-L1 act to restrict T-cell responses in cancer and contribute to self-tolerance. Consistent with this role, PD-1 checkpoint inhibitors have been associated with immune-related adverse events (irAEs), immune toxicities thought to be autoimmune in origin. Analyses of dermatological irAEs have identified an association with improved overall survival (OS) following anti-PD-(L)1 therapy, but the factors that contribute to this relationship are poorly understood. We collected germline whole genome sequencing data from IMvigor211, a recent phase 3 randomized controlled trial comparing atezolizumab (anti-PD-L1) monotherapy to chemotherapy in bladder cancer. We found that high vitiligo, high psoriasis, and low atopic dermatitis polygenic risk scores (PRSs) were associated with longer OS under anti-PD-L1 monotherapy as compared to chemotherapy, reflecting the Th17 polarization of these diseases. PRSs were not correlated with tumor mutation burden, PD-L1 immunohistochemistry, nor T-effector gene signatures. Shared genetic factors impact risk for dermatological autoimmunity and anti-PD-L1 monotherapy in bladder cancer.

genetics↗