Biology subjects

Yang, B.

Publications and source records attributed to Yang, B..

At least 199 records · Page 11Linked to original sources

bioRxiv2021

Lamina cribrosa vessel and collagen beam networks are distinct

Our goal was to analyze the spatial interrelation between vascular and collagen networks in the lamina cribrosa (LC). Specifically, we quantified the percentages of collagen beams with/without vessels and of vessels inside/outside of collagen beams. To do this, the vasculature of six normal monkey eyes was labelled by perfusion post-mortem. After enucleation, coronal cryosections through the LC were imaged using fluorescence and polarized light microscopy to visualize the blood vessels and collagen beams, respectively. The images were registered to form 3D volumes. Beams and vessels were segmented, and their spatial interrelationship was quantified in 3D. We found that 22% of the beams contained a vessel (range 14% to 32%), and 21% of vessels were outside beams (13% to 36%). Stated differently, 78% of beams did not contain a vessel (68% to 86%), and 79% of vessels were inside a beam (64% to 87%). Individual monkeys differed significantly in the fraction of vessels outside beams (p<0.01 by linear mixed effect analysis), but not in the fraction of beams with vessels (p>0.05). There were no significant differences between contralateral eyes in the percent of beams with vessels and of vessels outside beams (p>0.05). Our results show that the vascular and collagenous networks of the LC in monkey are clearly distinct, and the historical notions that each LC beam contains a vessel and all vessels are within beams are inaccurate. We postulate that vessels outside beams may be relatively more vulnerable to mechanical compression by elevated IOP than are vessels shielded inside of beams. Research highlights- We combined fluorescence and polarized light microscopy to map in 3D the lamina cribrosa vessels and collagen beams of three pairs of monkey eyes - Collagen beam and vessel networks of the lamina cribrosa have distinct topologies - Over half of lamina cribrosa collagen beams did not contain a blood vessel - One fifth of blood vessels in the lamina cribrosa were outside collagen beams - Beams with/without vessels and vessels inside/outside beams may respond differently to IOP

bioengineering↗

bioRxiv2021

Real-time imaging of optic nerve head collagen microstructure and biomechanics using instant polarized light microscopy

Current tools lack the temporal or spatial resolution necessary to image many important aspects of the architecture and dynamics of the optic nerve head (ONH). We evaluated the potential of instant polarized light microscopy (IPOL) to overcome these limitations by leveraging the ability to capture collagen fiber orientation and density in a single image. Coronal sections through the ONH of fresh normal sheep eyes were imaged using IPOL while they were stretched using custom uniaxial or biaxial micro-stretch devices. IPOL allows identifying ONH collagen architectural details, such as fiber interweaving and crimp, and has high temporal resolution, limited only by the frame rate of the camera. Local collagen fiber orientations and deformations were quantified using color analysis and image tracking techniques. We quantified stretch-induced collagen uncrimping of lamina cribrosa (LC) and peripapillary sclera (PPS), and changes in LC pore size (area) and shape (convexity and aspect ratio). The simultaneous high spatial and temporal resolutions of IPOL revealed complex ONH biomechanics: i) stretch-induced local deformation of the PPS was nonlinear and nonaffine. ii) under load the crimped collagen fibers in the PPS and LC straightened, without torsion and with only small rotations. iii) stretch-induced LC pore deformation was anisotropic and heterogeneous among pores. Overall, with stretch the pores were became larger, more convex, and more circular. We have demonstrated that IPOL reveals details of collagen morphology and mechanics under dynamic loading previously out of reach. IPOL can detect stretch-induced collagen uncrimping and other elements of the tissue nonlinear mechanical behavior. IPOL showed changes in pore morphology and collagen architecture that will help improve understanding of how LC tissue responds to load. HighlightsO_LIWe demonstrate that instant polarized light microscopy allows visualization and quantification of changes in optic nerve head collagen morphology and architecture under dynamic loading C_LIO_LIWe show crimped collagen fibers in the peripapillary sclera and lamina cribrosa straightening under load, without torsion and with only small rotations. C_LIO_LIWe show that stretch-induced local deformation of the peripapillary sclera was nonlinear and nonaffine. C_LIO_LIWe show that stretch-induced lamina cribrosa pore deformation was anisotropic and heterogeneous among pores. C_LIO_LIOur results show this novel imaging technique could help understand the role of collagen microstructure in eye physiology, aging, and in biomechanics-related diseases, such as glaucoma and myopia. C_LI

bioengineering↗

bioRxiv2021

Mapping brain-wide excitatory projectome of primate prefrontal cortex at submicron resolution: relevance to diffusion tractography

Resolving trajectories of axonal pathways in the primate prefrontal cortex remains crucial to gain insights into higher-order processes of cognition and emotion, which requires a comprehensive map of axonal projections linking demarcated subdivisions of prefrontal cortex and the rest of brain. Here we report a mesoscale excitatory projectome issued from the ventrolateral prefrontal cortex (vlPFC) to the entire macaque brain by using viral-based genetic axonal tracing in tandem with high-throughput serial two-photon tomography, which demonstrated prominent monosynaptic projections to other prefrontal areas, temporal, limbic and subcortical areas, relatively weak projections to parietal and insular cortices but no projections directly to the occipital lobe. In a common 3D space, we quantitatively validated an atlas of diffusion tractography-derived vlPFC connections with correlative enhanced green fluorescent protein-labelled axonal tracing, and observed generally good agreement except a major difference in the posterior projections of inferior fronto-occipital fasciculus. These findings raise an intriguing question as to how neural information passes along long-range association fiber bundles in macaque brains, and call for the caution of using diffusion tractography to map the wiring diagram of brain circuits.

neuroscience↗

bioRxiv2021

Synergistic interaction of hyposalinity stress with Vibrio infection causes mass mortalities in oysters by inducing host microflora imbalance and immune dysregulation

A sudden drop in salinity following extreme precipitation events usually causes mass mortalities of oysters exposed to pathogens in ocean environment. While how hyposalinity stress interacts with pathogens to cause mass mortality remains obscure. In this study, we performed an experiment by mimicking hyposalinity stress and pathogen infection with V. alginolyticus to investigate their synergistic effect on the mortality of infected oysters toward understanding of the interaction among environment, host, and pathogen. We showed that hyposalinity stress (10{per thousand}, 20{per thousand} versus 30{per thousand}) did not significantly affect proliferation and virulence of V. alginolyticus, but significantly altered microbial composition and diversity in infected oysters. Microbial community profiling by 16S rRNA sequencing revealed disrupted homeostasis of digestive bacterial microbiota with increased abundance of several pathogenic bacteria, which may affect the pathogenesis in oysters. Transcriptome profiling of infected oysters revealed that a large number of genes associated with apoptosis and inflammation were significantly induced under hyposalinity, suggesting that hyposalinity stress may have triggered immune dysregulation in infected oysters. This work provides significant information in decoding mechanisms of synergistic interaction among environment factors, host genetics, and digestive microbiota, and how they contribute to pathogenesis. IMPORTANCERevealing the response of oyster host and microbial community to the interference of multiple environmental factors is an important aspect of deciphering the complex pathogenic mechanism in oysters. We evaluated the synergistic effects of hyposalinity stress and Vibrio alginolyticus infection in oysters. Results showed that hyposalinity stress significantly caused mass mortalities of infected oysters by destroying digestive microbial community structure, and triggering excessive immune response in oysters. This work provides valuable information for deciphering the mechanisms of synergistic interaction among environmental factors, host, and pathogens, and how they contribute to pathogenesis.

pathology↗

bioRxiv2021

OsSWEET11b, a sixth leaf blight susceptibility gene involved in sugar transport-dependent male fertility

SWEETs play important roles in intercellular sugar transport. Induction of SWEET sugar transporters by transcription activator-like effectors (TALe) of Xanthomonas ssp. is a key factor for bacterial leaf blight (BLB) infection of rice, cassava and cotton. Here, we identified the so far unknown OsSWEET11b with roles in male fertility and BLB susceptibility in rice. While single ossweet11a or b mutants were fertile, double mutants were sterile. Since clade III SWEETs can transport gibberellin (GA), a key hormone for rice spikelet fertility, sterility and BLB susceptibility might be explained by GA transport deficiencies. However, in contrast to the Arabidopsis homologs, OsSWEET11b did not mediate detectable GA transport. Fertility and susceptibility must therefore depend on SWEET11b-mediated sucrose transport. Ectopic induction of OsSWEET11b by designer TALe enables TALe-free Xanthomonas oryzae pv. oryzae (Xoo) to cause disease, identifying OsSWEET11b as a BLB susceptibility gene and demonstrating that the induction of host sucrose uniporter activity is key to virulence of Xoo. Notably, only three of now six clade III SWEETs are targeted by known Xoo strains from Asia and Africa. The identification of OsSWEET11b has relevance in the context of fertility and for protecting rice against emerging Xoo strains that evolve TALes to exploit OsSWEET11b.

plant biology↗

bioRxiv2021

Modulating D1 rather than D2 receptor-expressing spiny-projection neurons corresponds to optimal antipsychotic effect

Overactive dopamine transmission in psychosis is predicted to unbalance striatal output via D1- and D2-dopamine receptor-expressing spiny-projection neurons (SPNs). Antipsychotic drugs are thought to re-balance this output by blocking D2-receptor signaling. Here we imaged D1- and D2-SPN Ca2+ dynamics in mice to determine the neural signatures of antipsychotic effect. Initially we compared effective (clozapine and haloperidol) antipsychotics to a candidate drug that failed in clinical trials (MP-10). Clozapine and haloperidol normalized hyperdopaminergic D1-SPN dynamics, while MP-10 only normalized D2-SPN activity. Clozapine, haloperidol or chemogenetic manipulations of D1-SPNs also normalized sensorimotor gating. Given the surprising correlation between clinical efficacy and D1-SPN modulation, we evaluated compounds that selectively target D1-SPNs. D1R partial agonism, antagonism, or positive M4 cholinergic receptor modulation all normalized the levels of D1-SPN activity, locomotion, and sensorimotor gating. Our results suggest that D1-SPN activity is a more relevant therapeutic target than D2-SPN activity for the development of effective antipsychotics.

neuroscience↗

bioRxiv2021

The swine spatiotemporal H3K27ac spectrum provides novel resources for exploring gene regulation related to complex traits and fundamental biological process

The limited knowledge of genomic non-coding and regulatory regions has limited our ability to decipher the genetic mechanisms underlying complex traits in pigs. In this study, we characterize the spatiotemporal landscape of putative enhancers and promoters and their target genes by combining H3K27ac targeted ChIP-Seq and RNA-Seq in fetal (day 74-75 pc) and adult (day 132-150 pn) tissues (brain, liver, heart, muscle and small intestine) sampled from Asian aboriginal Bamaxiang and European highly selected Large White pigs of both sexes. We identify 101,290 H3K27ac peaks marking 18,521 promoters and 82,769 enhancers, including peaks that are active across all tissues and developmental stages could indicate safe harbors for exogenous gene insertion, and tissue and developmental-stage specific peaks that regulate genes pathways matching tissue and developmental stage specific physiological functions. We found H3K27ac and DNA methylation in the promoter region of the XIST gene may involve in X chromosome inactivation, and demonstrate utility of the present resource to reveal regulatory patterns of known causal genes and to prioritize candidate causal variants for complex traits in pigs. We have developed a web browser to improve the accessibility of the results (http://39.108.231.116/browser/?genome=susScr11).

genomics↗

bioRxiv2021

High-throughput production of functional prototissues capable of producing NO for vasodilation

Bottom-up synthesis of prototissues helps us to understand the internal cellular communications in the natural tissues and their functions, as well as to improve or repair the damaged tissues. The existed prototissues are rarely used to improve the function of living tissues. We demonstrated a methodology to produce spatially programmable prototissues based on the magneto-Archimedes effect in a high-throughput manner. More than 2000 prototissues are produced once within 2 hours. Two-component and three-component spatial coded prototissues are fabricated by varying the addition giant unilamellar vesicles (GUVs) order/number, and the magnetic field distributions. Two-step and three-step signal communications in the prototissues are realized using cascade enzyme reactions. More importantly, the two-component prototissues capable of producing nitric oxide (NO) cause vasodilation of rat blood vessels in the presence of glucose and hydroxyurea. The tension force decreases 2.59 g, meanwhile the blood vessel relaxation is of 31.2%. Our works pave the path to fabricate complicated programmable prototissues, and hold great potential in tissue transplantation in the biomedical field.

bioengineering↗

bioRxiv2021

Gating mechanism of human N-type voltage-gated calcium channel

N-type voltage-gated calcium (CaV) channels mediate Ca2+ influx at the presynaptic terminals in response to action potential and play vital roles in synaptogenesis, neurotransmitter releasing, and nociceptive transmission. Here we elucidate a cryo-electron microscopy (cryo-EM) structure of the human CaV2.2 complex at resolution of 2.8 [A]. This complex structure reveals how the CaV2.2, {beta}1, and 2{delta}1 subunits are assembled. In our structure, the second voltage-sensing domain (VSD) is stabilized at a resting-state conformation, which is distinct from the other three VSDs of CaV2.2 as well as activated VSDs observed in previous structures of CaV channels. The structure also shows that the intracellular gate formed by S6 helices is closed, and a W-helix from the DII-III linker is determined to act as a blocking-ball that causes closed-state inactivation in CaV2.2. Collectively, our structure provides previously unseen structural insights into fundamental gating mechanisms of CaV channels.

neuroscience↗

bioRxiv2021

The phosphatidylglycerol phosphate synthase PgsA utilizes a trifurcated amphipathic cavity for catalysis at the membrane-cytosol interface

Phosphatidylglycerol is a crucial phospholipid found ubiquitously in biological membranes of prokaryotic and eukaryotic cells. The phosphatidylglycerol phosphate (PGP) synthase (PgsA), a membrane-embedded enzyme, catalyzes the primary reaction of phosphatidylglycerol biosynthesis. Mutations in pgsA frequently correlate with daptomycin resistance in Staphylococcus aureus and other prevalent infectious pathogens. Here we report the structures of S. aureus PgsA (SaPgsA) captured at two distinct states of the catalytic process, with lipid substrate (cytidine diphosphate-diacylglycerol, CDP-DAG) or product (PGP) bound to the active site within a trifurcated amphipathic cavity. The hydrophilic head groups of CDP-DAG and PGP occupy two different pockets in the cavity, inducing local conformational changes. An elongated membrane-exposed surface groove accommodates the fatty acyl chains of CDP-DAG/PGP and opens a lateral portal for lipid entry/release. Remarkably, the daptomycin resistance-related mutations mostly cluster around the active site, causing reduction of enzymatic activity. Our results provide detailed mechanistic insights into the dynamic catalytic process of PgsA and structural frameworks beneficial for development of antimicrobial agents targeting PgsA from pathogenic bacteria.

biophysics↗

bioRxiv2021

Mapping the host protein interactome of non-coding regions in SARS-CoV-2 genome

A deep understanding of SARS-CoV-2-host interactions is crucial to the development of effective therapeutics. The role of non-coding regions of viral RNA (ncrRNAs) has not been scrutinized. We developed a method using MS2 affinity purification coupled with liquid chromatography-mass spectrometry (MAMS) to systematically map the interactome of SARS-CoV-2 ncrRNA in different human cell lines. Integration of the results defined the core and cell-type-specific ncrRNA-host protein interactomes. The majority of ncrRNA-binding proteins were involved in RNA biogenesis, protein translation, viral infection, and stress response. The 5' UTR interactome is enriched with proteins in the snRNP family and is a target for the regulation of viral replication and transcription. The 3' UTR interactome is enriched with proteins involved in the cytoplasmic RNP granule (stress granule) and translation regulation. We show that the ORF10 is likely to be a part of 3' UTR. Intriguingly, the interactions between negative-sense ncrRNAs and host proteins, such as translation initiation factors and antiviral factors, suggest a pathological role of negative-sense ncrRNAs. Moreover, the cell-type-specific interactions between ncrRNAs and mitochondria may explain the differences of cell lines in viral susceptibility. Our study unveils a comprehensive landscape of the functional SARS-CoV-2 ncrRNA-host protein interactome, providing a new perspective on virus-host interactions and the design of future therapeutics.

genomics↗

bioRxiv2021

ZAF -- An Open Source Fully Automated Feeder for Aquatic Facilities

In the past few decades, aquatic animals have become popular model organisms in biology, spurring a growing need for establishing aquatic facilities. Zebrafish are widely studied and relatively easy to culture using commercial systems. However, a challenging aspect of maintaining aquatic facilities is animal feeding, which is both time- and resource-consuming. We have developed an open-source fully automatic daily feeding system, Zebrafish Automatic Feeder (ZAF). ZAF is reliable, provides a standardized amount of food to every tank, is cost-efficient and easy to build. The advanced version, ZAF+, allows for the precise control of food distribution as a function of fish density per tank, and has a user-friendly interface. Both ZAF and ZAF+ are adaptable to any laboratory environment and facilitate the implementation of aquatic colonies. Here we provide all blueprints and instructions for building the mechanics, electronics, fluidics, as well as to setup the control software and its user-friendly graphical interface. Importantly, the design is modular and can be scaled to meet different user needs. Furthermore, our results show that ZAF and ZAF+ do not adversely affect zebrafish culture, enabling fully automatic feeding for any aquatic facility.

developmental biology↗

bioRxiv2021

Rapid, modular biosynthesis of plant hemicellulose and its impact on yeast cells

BackgroundThe carbohydrate polymers that encapsulate plants cells have benefited humans for centuries and have valuable biotechnological uses. In the past five years, exciting possibilities have emerged in the engineering of polysaccharide-based biomaterials. Despite impressive advances on bacterial cellulose-based hydrogels, comparatively little is known about how plant hemicelluloses can be reconstituted and modulated in cells suitable for biotechnological purposes. ResultsHere, we assembled cellulose synthase-like A (CSLA) enzymes using an optimized Pichia pastoris platform to produce tunable heteromannan (HM) polysaccharides in yeast. By swapping the domains of plant mannan and glucomannan synthases, we engineered chimeric CSLA proteins that made {beta}-1,4-linked mannan in quantities surpassing those of the native enzymes while minimizing the burden on yeast growth. Prolonged expression of a glucomannan synthase from Amorphophallus konjac was toxic to yeast cells: reducing biomass accumulation and ultimately leading to compromised cell viability. However, an engineered glucomannan synthase as well as CSLA pure mannan synthases and a CSLC glucan synthase did not inhibit growth. Interestingly, Pichia cell size could be increased or decreased depending on the composition of the CSLA protein sequence. HM yield and glucose incorporation could be further increased by co-expressing chimeric CSLA proteins with a MANNAN-SYNTHESIS-RELATED (MSR) co-factor from Arabidopsis thaliana. ConclusionThe results provide novel routes for the engineering of polysaccharide-based biomaterials that are needed for a sustainable bioeconomy. The characterization of chimeric cellulose synthase-like enzymes in yeast offers an exciting avenue to produce plant polysaccharides in a tunable manner. Furthermore, cells modified with non-toxic plant polysaccharides such as {beta}-mannan offer a modular chassis to produce and encapsulate sensitive cargo such as therapeutic proteins.

bioengineering↗

bioRxiv2021

Virtual Parts Repository 2: Model-driven design of genetic regulatory circuits

Engineering genetic regulatory circuits is key to the creation of biological applications that are responsive to environmental changes. Computational models can assist in understanding especially large and complex circuits where manual analysis is infeasible, permitting a model-driven design process. However, there are still few tools that offer the ability to simulate the system under design. One of the reasons for this is the lack of accessible model repositories or libraries that cater for the modular composition of models of synthetic systems that do not yet exist in nature. Here, we present the Virtual Parts Repository 2, a resource to facilitate the model-driven design of genetic regulatory circuits, which provides reusable, modular and composable models. The repository is service-oriented and can be utilized by design tools in computational workflows. Designs provided in Synthetic Biology Open Language documents are used to derive system-scale and hierarchical Systems Biology Markup Language models. We also present a rule-based modeling abstraction based on reaction networks to facilitate scalable and modular modeling of complex and large designs. This modeling abstraction incorporates design patterns such as roadblocking, distributed deployment of genetic circuits using plasmids and cellular resource dependency. The computational resources and the modeling abstraction presented in this paper allow computational design tools to take advantage of computational simulations and ultimately help facilitate more predictable applications. Graphical TOC Entry O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/439316v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@be045dorg.highwire.dtl.DTLVardef@110856forg.highwire.dtl.DTLVardef@1a861eforg.highwire.dtl.DTLVardef@1b5cf48_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗

bioRxiv2021

An artificial cell containing cyanobacteria for endosymbiosis mimicking

The bottom-up constructed artificial cells help to understand the cell working mechanism and provide the evolution clues for organisms. Cyanobacteria are believed to be the ancestors of chloroplasts according to endosymbiosis theory. Herein we demonstrate an artificial cell containing cyanobacteria to mimic endosymbiosis phenomenon. The cyanobacteria sustainably produce glucose molecules by converting light energy into chemical energy. Two downstream "metabolic" pathways starting from glucose molecules are investigated. One involves enzyme cascade reaction to produce H2O2 (assisted by glucose oxidase) first, followed by converting Amplex red to resorufin (assisted by horseradish peroxidase). The more biological one involves nicotinamide adenine dinucleotide (NADH) production in the presence of NAD+ and glucose dehydrogenase. Further, NADH molecules are oxidized into NAD+ by pyruvate catalyzed by lactate dehydrogenase, meanwhile, lactate is obtained. Therefore, the sustainable cascade cycling of NADH/NAD+ is built. The artificial cells built here simulate the endosymbiosis phenomenon, meanwhile pave the way for investigating more complicated sustainable energy supplied metabolism inside artificial cells.

synthetic biology↗

bioRxiv2021

Gene structure, differential exon usage, and expression of the testis long intergenic non-protein coding RNA 1016 in humans reveals isoform-specific roles in controlling biological processes

Long noncoding RNAs (lncRNAs) have emerged as critical regulators of biological processes. The constant expansion of newly-identified lncRNA genes requires that each one be comprehensively annotated to understand its molecular functions. Here, we describe a detailed characterization of the gene which encodes long intergenic non-protein coding RNA 01016 (LINC01016, a.k.a., LncRNA1195) with a focus on its structure, exon usage, and expression in human and macaque tissues. In this study, we show that it is exclusively conserved among non-human primates, suggesting its recent evolution and is expressed and processed into 12 distinct RNAs in testis, cervix, and uterus tissues. Further, we integrate de novo annotation of expressed LINC01016 transcripts and isoform-dependent gene expression analyses to show that human LINC01016 is a multi-exon gene, processed through differential exon usage with isoform-specific functions. Furthermore, in gynecological cancers, such as cervical squamous cell carcinoma and uterine corpus endometrial carcinoma, LINC01016 is downregulated; however, its higher expression is predictive of relapse-free survival in these cancers. Collectively, these analyses reveal that, unlike coding RNAs, lncRNA isoforms are differentially regulated and precisely processed in specific tissues to perform distinct biological roles. One sentence summaryThe distinct molecular role of LINC01016 isoforms reveals intricate biology associated with lncRNA transcription and processing.

genomics↗

bioRxiv2021

Optimizing mechanostable anchor points of engineered lipocalin in complex with CTLA-4

We used single-molecule AFM force spectroscopy (AFM-SMFS) to screen residues along the backbone of a non-antibody protein binding scaffold (lipocalin/anticalin), and determine the optimal anchor point that maximizes binding strength of the interaction with its target (CTLA-4). By incorporating non-canonical amino acids into anticalin, and using click chemistry to attach an Fg{beta} peptide at internal sequence positions, we were able to mechanically dissociate anticalin from CTLA-4 by pulling from eight different anchoring residues using an AFM cantilever tip. We found that pulling on the anticalin from residue 60 or 87 resulted in significantly higher rupture forces and a decrease in koff by 2-3 orders of magnitude over a force range of 50-200 pN. Five of the six internal pulling points tested were significantly more stable than N- or C-terminal anchor points, rupturing at up to 250 pN at loading rates of 0.1-10 nN sec-1. Anisotropic network modelling and molecular dynamics simulations using the G[o]-MARTINI approach explained the mechanism underlying the geometric dependency of mechanostability. These results suggest that optimization of attachment residue position for therapeutic and diagnostic cargo can provide large improvements in binding strength, allowing affinity maturation without requiring genetic mutation of binding interface residues.

biophysics↗

bioRxiv2021

Periodic synchronization of dengue epidemics in Thailand: the roles played by temperature and immunity

The spatial distribution of dengue and its vectors (spp. Aedes) may be the widest it has ever been, and projections suggest that climate change may allow the expansion to continue. However, the largest impacts of climate change on dengue might be in regions where the pathogen is already endemic. In these areas, the waxing and waning of immunity has a large impact on temporal dynamics of cases of dengue haemorrhagic fever. Here, we use 51 years of data across 72 provinces and characterise spatio-temporal patterns of dengue in Thailand, where dengue has caused almost 1.5 million cases over the last thirty years, and examine the roles played by temperature and dynamics of immunity in giving rise to those patterns. We find that timescales of multiannual oscillations in dengue vary in space and time and uncover an interesting spatial phenomenon: Thailand has experienced multiple, periodic synchronization events. We show that patterns in synchrony of dengue are consistent with those observed in temperature. Applying a temperature-driven dengue model, we explore how dynamics of immunity interact with temperature to produce the observed multiannual dynamics and patterns in synchrony. While multiannual oscillations are readily produced by immunity in absence of multiannual timescales in temperature, synchrony in temperature can synchronise dengue dynamics in different locations. However, at higher mean temperatures and lower seasonal variation, immune dynamics become more predominant, and dengue dynamics become more insensitive to multiannual fluctuations in temperature. These findings can help underpin predictions of disease patterns as global temperatures rise. Author summary

ecology↗