Biology subjects

Kuang, Y.

Publications and source records attributed to Kuang, Y..

At least 19 recordsLinked to original sources

bioRxiv2026

A generalized resource-allocation growth law reveals mechanisms of differential responses to intermittent androgen deprivation therapy in prostate cancer

Resource-limited growth frameworks often developed independently. Here, we derived a growth law by assuming a cell balancing internal competing resource demands and generalizing the growth signal through a shape parameter h, the trade-off exponent. In Liebig's single-limiting-resource regime, it recovers Droop's cell quota at h=1 and approaches Prater's growth efficiency as h grows large. h determines how sharply growth declines when allocation departs from optimal, thereby shaping populations evolution. Cyclic environmental stress tests such growth laws. Hence, we built a model from this growth law and applied it to prostate cancer growth in patients undergoing cyclic intermittent androgen deprivation therapy. We showed the model recapitulated longitudinal prostate specific antigen (PSA) and serum androgen measurements from 71 prostate cancer patients using a nonlinear mixed-effects framework (pooled and median individual R^2 {approx} 0.9 for PSA and {approx} 0.8 for serum androgen). h is well-constrained by the data and separates treatment outcomes (success vs. failure, p = 0.003). The results predict that failing cases have cancer that can adapt to a wide range of growth conditions with minimal cost. A simplified model recapitulated PSA dynamics from 32 prostate cancer patients on cyclic adaptive therapy (R^2 {approx} 0.8). Estimates of h for castration resistant cancer in adaptive cohort were similar to failure cases in the intermittent cohort. We found no statistical differences in estimated parameters between the adaptive vs. standard of care arms, suggesting that adaptive schedule may drive the differential outcome. The results support this growth law, providing a foundation for resource-limited growth across biological systems.

ecology↗

bioRxiv2026

Heat stress-induced condensation of G3BP1 in perinuclear P-bodies in C. elegans' germline

Stress granules (SGs) are essential subcellular assemblies that enable cells to adapt to environmental stress, and their dynamic assembly and disassembly are critical for maintaining cellular homeostasis and reproductive capacity. However, the function and regulation of stress granules in germline cells remain mysterious. In this study, we characterized the function of GTBP-1, the homolog of human G3BP1, in response to heat stress in Caenorhabditis elegans and elucidated its regulation in stress granule dynamics. gtbp-1 mutants exhibit pronounced temperature-dependent biodirectional reproductive characteristics. At lower temperatures, their brood size is higher than that of wild-type animals, whereas at 25 {degrees}C they are completely sterile. GTBP-1 is diffusely distributed at normal culturing temperatures but forms perinuclear stress granules upon heat shock in the germline. While the NTF2 domain is essential for germline stress granule formation, other domains, including the IDR, RRM and RGG, are required for the recovery phase after heat shock. GTBP-1 stress granules colocalize with the P-bodies, but not with other germ granules. The depletion of P-bodies prohibited the perinuclear GTBP-1 stress granule formation. A combination of forward genetic screening together with RNAi-based candidate screening identified the P body components, the RNA helicase LAF-1, the SUMO protein SMO-1, and the mTOR pathway effector RSKS-1(S6K) as key regulators of GTBP-1 germline stress granule formation. Together, this work revealed that germline stress granules may be subjected to multiple layers of regulations and GTBP-1 may safeguards reproductive homeostasis under temperature stress by coordinating germline stress granule condensation. Author SummaryReproduction is particularly vulnerable to environmental stress, yet germ cells must remain functional to ensure fertility. How germ cells protect themselves under stressful conditions is still not well understood. In this study, we used the nematode Caenorhabditis elegans to examine how germ cells respond to heat stress, focusing on GTBP-1, a conserved protein involved in stress granule formation. We found that GTBP-1 plays contrasting roles depending on temperature: under normal conditions it restrains reproduction, whereas under heat stress it becomes essential for maintaining fertility. When animals are exposed to elevated temperature, GTBP-1 rapidly forms granules around the nuclei of germ cells, these granules assemble at sites occupied by processing bodies, another type of RNA-containing structure, revealing a close spatial relationship between two stress-responsive compartments. We also found that this process is regulated by conserved factors involved in RNA regulation and nutrient-responsive signaling. Together, our findings show how germ cells reorganize RNA-protein assemblies to preserve reproductive capacity under stressful conditions.

genetics↗

bioRxiv2026

SUMO2 Deletion Changes Chromatin Accessibility and Enhances Cytotoxic T Cell Activation and Tumor Infiltration

Cytotoxic T cells (CTL) are crucial for adaptive immunity that leads to prolonged survival and potential cures for cancer. Recent clinical data has shown that pharmacological inhibition of SUMOylation (SUMOi) profoundly modifies tumor microenvironment (TME) and activates CTL, although the mechanism is not well described. In this study, we found that T cell specific knock out (KO) of the most dominant SUMO paralog, Sumo2/SUMO2, in both mouse and human CD8+ T cells significantly enhanced CD8+ T cell activation that is independent of the known mechanism - inducing type I IFN (IFN-I) expression by myeloid cells. Sumo2/SUMO2 KO in CD8+ T cells increased chromatin accessibility for transcription factors BATF, JunB, ATF3, FRA1, FRA2, and AP1 that are known to promote T cell activation and proliferation. Using antigen-specific T cell models, OT1 and Chimeric Antigen Receptor (CAR)-T cells, we found that Sumo2 KO CD8+ T cells had significantly higher tumor infiltration as revealed by flow cytometry, immuno-fluorescence (IF) staining, and single nuclei RNA-sequencing (snRNA-seq) and conferred greater tumor growth inhibition than wildtype (WT) control T cells. snRNA-seq also revealed Sumo2 KO CD8+ T cells increased the expression of Tumor Necrosis Factor-Related Apoptosis-inducing Ligand (TRAIL), induced apoptosis genes in tumor cells and activated IFN-I and IFN-{gamma} responsive genes in all cell types in the TME. These findings elucidate a novel mechanism regarding how SUMOylation can directly control CTL activation and tumor infiltration that activate anti-tumor immunity in the TME. SUMO2 KO can also be a potential strategy to enhance adoptive T cell therapies of solid tumors by enhancing their activity, tumor infiltration and their ability to after the TME.

immunology↗

bioRxiv2025

Dynamic PD-L1 Regulation Shapes Tumor Immune Escape andResponse to Immunotherapy

A major challenge in cancer treatment is the ability of tumor cells to adapt to immunotherapy through immune escape, often mediated by the PD-1/PD-L1 pathway. To investigate this, we adapted an ordinary differential equation model of combination therapy, incorporating the dynamics of the immune checkpoint inhibitor Avelumab and the immunostimulant NHS-muIL12. Using literature-derived parameter values from a previous study, we refitted a single parameter across therapies, which showed that PD-L1 expression increased with immunotherapy, while Avelumab blocked its functional signaling, preventing PD-L1 from suppressing T-cell activity. Incorporating therapy-dependent, dynamically regulated PD-L1 expression enabled a biologically grounded mechanism to reproduce experimental observations, leading us to formulate PD-L1 tumor expression as a dynamic variable ({epsilon}) and providing a mechanistic basis for both therapeutic synergy and treatment failure. Our results indicate that tumor resistance is linked to dose-dependent upregulation of PD-L1 following NHS-muIL12 treatment, explaining treatment failure, while PD-1/PD-L1 blockade in combination therapy enables effective anti-tumor immune responses.

cancer biology↗

bioRxiv2025

Baseline expression of c-Myc defines the tissue specificity of oncogenic K-Ras

KRAS is among the most frequently mutated oncogenes in cancer. Yet, mutations in KRAS are common only in tumors originating from a subset of tissues. It is critical to understand the molecular mechanisms underlying this oncogene tissue specificity. Utilizing genetically engineered mouse models carrying a conditional oncogenic allele of Kras, we expressed activated K-Ras in adult tissues to investigate its specificity. We discovered that the ability of K-RasG12D to influence the fitness of cells in a given tissue is not determined by its canonical signaling through MAPK. Instead, low baseline expression of c-Myc renders tissues non-permissive to oncogenic K-Ras, a context that can be reversed in the liver by ectopically expressing c-Myc. This functions independently of the proliferative index of the tissue or the induction of cell cycle arrest or apoptosis. Our findings reveal the importance of the basal state of the tissue-inherent signaling network for determining oncogene specificity.

cancer biology↗

bioRxiv2025

De novo designed bright, hyperstable rhodamine binders for fluorescence microscopy

De novo protein design has emerged as a powerful strategy with the promise to create new tools. The practical performance of designed fluorophore binders, however, has remained far from meeting fluorescence microscopy demands. Here, we design de novo Rhodamine Binder (Rhobin) tags that combine ideal properties including size, brightness, and now adding hyperstability. Rhobin allows live and fixed cell imaging of a wide range of subcellular targets in mammalian cells. Its reversible fluorophore binding further enables live super-resolution STED microscopy with low photobleaching, as well as PAINT-type single-molecule localization microscopy. We showcase Rhobin in the extremophile Sulfolobus acidocaldarius living at 75{degrees}C, an application previously inaccessible by existing tags. Rhobin will serve as the basis for a new class of live cell fluorescent tags and biosensors.

bioengineering↗

bioRxiv2025

The H3K27me3 reader UAD-2 recruits a TAF-12-containing transcription condensates to initiate piRNA expression within heterochromatic clusters

Metazoans utilize the small RNA pathway to regulate gene expression and maintain genome integrity. This pathway directs histone H3 lysine 9 tri-methylation (H3K9me3) or histone H3 lysine 27 tri-methylation (H3K27me3) at target loci to induce transcriptional gene silencing. Interestingly, some small RNAs are generated from genomic loci enriched in H3K9me3 or H3K27me3. However, the transcription mechanism of small RNA precursors from these heterochromatic regions remains unclear. In C. elegans, piRNAs originate from two genomic clusters enriched with H3K27me3 marks, which recruit the H3K27me3 reader UAD-2 and the upstream sequence transcription complex (USTC). Here, we demonstrate that piRNA transcription in C. elegans relies on TAF-12, a subunit of the basal transcription factor IID (TFIID). Depletion of TAF-12 reduces the production of both piRNA precursors and mature piRNAs. TAF-12 interacts with UAD-2 and facilitates piRNA focus formation in germ cell nuclei. We further show that TAF-12 triggers piRNA transcription by recruiting the RNA polymerase II subunit RPB-5, the Mediator complex subunit MDT-8, and the general transcription factors GTF-2F2 and GTF-2H2C. Thus, piRNA transcription within heterochromatic regions depends on the collaboration between histone modification readers, piRNA-specific transcription factors, and core transcription machinery.

genetics↗

bioRxiv2025

In Situ Detection of α-Synuclein Seeding Activity Using Quiescent Seed Amplification Assay

The prion-like propagation of proteopathic -synuclein (Syn) "seeds" is a central pathogenic mechanism in synucleinopathies. However, methods to directly visualize this "seeding activity" within intact tissue are lacking. Conventional antibody-based techniques provide only static snapshots of pathological deposits, while sensitive seed amplification assays lose spatial information via mechanical fragmentation. Here, we introduce the Syn Quiescent Seed Amplification Assay (QSAA), a method for specific, robust, in situ amplification of Syn seeds directly within tissue sections. QSAA demonstrates superior sensitivity and earlier detection than pS129 and ThS staining, revealing widespread seeding in a PD mouse model, and successfully identifies endogenous seeds in archival human brains. By integrating with immunofluorescence, IF-QSAA uncovered microglial seeding activity and established that pS129 phosphorylation and seeding activity represent distinct pathological states. This offers unprecedented spatial insights into synucleinopathy pathogenesis, holding significant promises for early diagnosis and therapeutic evaluation.

neuroscience↗

bioRxiv2025

Immunomodulation of Pancreatic Cancer via Inhibition of SUMOylation and CD155/TIGIT Pathway

Pancreatic ductal adenocarcinoma (PDAC) is the deadliest major cancer and has a profoundly immunosuppressive tumor microenvironment (TME). Previous studies have shown that inhibition of the E1 enzyme, which catalyzes the small ubiquitin-like modifiers (SUMO), with the small molecule TAK-981, can reprogram the TME to enhance immune activation and suppress tumor growth. We found that the CD-155/TIGIT pathway, a key regulator of immune evasion in PDAC, is influenced by SUMOylation. We hypothesized that the combination of SUMO E1 and TIGIT inhibition would synergistically induce anti-tumor immune effects. We used a clinically relevant orthotopic mouse model that consistently develops liver metastases to study this combination therapy alone and in the perioperative setting with surgical resection. The combination of SUMO E1 and TIGIT inhibition significantly prolonged survival. Complete responders exhibited protective immunity and enhanced T cell reactivity to model-specific alloantigens. Complementary immune analyses of resected tumors demonstrated that combination therapy more significantly reduces the abundance of regulatory FOXP3+CD4+ T cells than each monotherapy alone. The findings suggest that SUMO E1 inhibition enhances antibody-mediated elimination of Tregs through innate immune cells, potentially by activation of type I interferon responses. Our results highlight a mechanism to enhance the efficacy of anti-TIGIT therapy. Brief SummarySUMOylation is a post-translational modification process critical for cancer. Inhibition of SUMOylation can improve the sensitivity of pancreatic cancer to immune checkpoint inhibition.

cancer biology↗

bioRxiv2025

Accessible and accurate cytometry analysis using fluorescence microscopes

We have developed a method along with a python-based analysis tool to capture images and produce flow cytometry like data utilizing simple accessible microscopes. Utilizing the recently developed generalist algorithms for cell segmentation, our approach easily segments semi-adherent or suspended cells facilitating quantification of fluorescent intensity similar to flow cytometry. We have shown that our approach exhibits similar speed and enhanced sensitivity when compared to typical flow cytometry. The utility of our approach is demonstrated by screening a set of 88 prime editing conditions utilizing the integration of mNeonGreen11 as a reporter.

cell biology↗

bioRxiv2025

Trans-generational maintenance of mitochondrial DNA integrity in oocytes during early folliculogenesis

Mutations in mitochondrial DNA (mtDNA) can lead to mitochondrial and cellular dysfunction. However, recent studies suggest that there is purifying selection against mutant mtDNAs during transgenerational transmission. We investigated the mtDNA dynamics during ovarian follicle development. Using base-editing, we generated mice harboring a 3177 G>A mutation corresponding to the human Leber hereditary optic neuropathy (LHON)-related mtDNA mutation and confirmed the transgenerational reduction of mutant mtDNA. Using a mouse follicle culture system in which pathogenic mtDNA mutations were introduced in vitro followed by mtDNA sequencing and digital PCR, we found this germline heteroplasmy shift during early folliculogenesis was induced by the decrease of mutant mtDNA together with compensatory replication of wild-type mtDNA. In contrast, synonymous mtDNA mutations did not impact the mtDNA dynamics. These findings show that mice can eliminate certain pathogenic mtDNA mutations in the germline during early folliculogenesis, maintaining mitochondrial integrity across generations.

genetics↗

bioRxiv2023

Global stability and parameter analysis reinforce therapeutic targets of PD-L1-PD-1 and MDSCs for glioblastoma

Glioblastoma (GBM) is an aggressive primary brain cancer that currently has minimally effective treatments. Like other cancers, immunosuppression by the PD-L1-PD-1 immune checkpoint complex is a prominent axis by which glioma cells evade the immune system. Myeloid-derived suppressor cells (MDSCs), which are recruited to the glioma microenviroment, also contribute to the immunosuppressed GBM microenvironment by suppressing T cell functions. In this paper, we propose a GBM-specific tumor-immune ordinary differential equations model of glioma cells, T cells, and MDSCs to provide theoretical insights into the interactions between these cells. Equilibrium and stability analysis indicates that there are unique tumorous and tumor-free equilibria which are locally stable under certain conditions. Further, the tumor-free equilibrium is globally stable when T cell activation and the tumor kill rate by T cells overcome tumor growth, T cell inhibition by PD-L1-PD-1 and MDSCs, and the T cell death rate. Bifurcation analysis suggests that a treatment plan that includes surgical resection and therapeutics targeting immune suppression caused by the PD-L1-PD1 complex and MDSCs results in the system tending to the tumor-free equilibrium. Using a set of preclinical experimental data, we implement the Approximate Bayesian Computation (ABC) rejection method to construct probability density distributions that estimate model parameters. These distributions inform an appropriate search curve for global sensitivity analysis using the extended Fourier Amplitude Sensitivity Test (eFAST). Sensitivity results combined with the ABC method suggest that parameter interaction is occurring between the drivers of tumor burden, which are the tumor growth rate and carrying capacity as well as the tumor kill rate by T cells, and the two modeled forms of immunosuppression, PD-L1-PD-1 immune checkpoint and MDSC suppression of T cells. Thus, treatment with an immune checkpoint inhibitor in combination with a therapeutic targeting the inhibitory mechanisms of MDSCs should be explored.

cancer biology↗

bioRxiv2022

Generate a new crucian carp (Carassius auratus) strain without intermuscular bones by knocking out bmp6

Elimination of intermuscular bones (IMBs) is vital to the aquaculture industry of cyprinids. In our previous study, we characterized bmp6 as essential in the development of IMBs in zebrafish. Knockout of bmp6 results in the absence of IMBs in zebrafish without affecting growth and reproduction. Therefore, we hypothesized that bmp6 could be used to generate new cyprinid strains without IMBs by gene editing. In this study, we established a gene editing strategy for knocking out the two orthologs of bmp6 in diploid crucian carp (Carassius auratus). We obtained an F3 population with both orthologs knocked out, in which no IMBs were detected by bone staining and X-ray, indicating that the new strain without IMBs (named WUCI strain) was successfully generated. Furthermore, we extensively evaluated the performance of the new strain in growth, reproduction, nutrient components, muscle texture and structure, and metabolites in muscle. The results showed that the WUCI strain grew faster than the wild-type crucian carp at 4-month-age. The reproductive performance and flesh quality did not show significant differences between the WUCI strain and wild-type crucian carp. Moreover, the metabolomics analysis suggested that the muscle tissues of the WUCI strain significantly enriched some metabolites belonging to the Thiamine metabolism, Nicotinate and Nicotinamide Metabolism pathway, which plays beneficial effects in anti-aging, anti-oxidant, and anti-radiation damage. In conclusion, we established a strategy to eliminate IMBs in crucian carp and obtain a WUCI strain whose performance was expected compared to the wild-type crucian carp; meanwhile, the WUCI strain enriched some beneficial metabolites to human health in muscle tissue. This study is the first report that a farmed cyprinid strain without IMBs, which could be stably inherited, was obtained worldwide; it provided excellent germplasm for the cyprinids aquaculture industry and a useful molecular tool for eliminating IMBs in other cyprinids.

genetics↗

bioRxiv2022

Rescue of aged muscle stem cell intrinsic quiescence defects by AKT inhibition revealed with a 3D biomimetic culture assay

Adult skeletal muscle harbors a population of muscle stem cells (MuSCs) that are required to repair or reform multinucleated myofibers after tissue injury. In youth, MuSCs return to a reversible state of cell cycle arrest termed quiescence after injury resolution. By contrast, a proportion of MuSCs in aged muscle remain in a semi-activated state, causing a premature response to subsequent injury cues that results in incomplete tissue repair and eventual stem cell depletion. Regulation of the balance between MuSC quiescence and activation in youth and in age may hold the key to restoring tissue homeostasis with age, but is incompletely understood. To fill this gap, we developed a simple and tractable in vitro method, with a 96-well footprint, to rapidly inactivate MuSCs freshly isolated from young skeletal muscle tissue, and return them to a quiescent-like state for at least one-week. This was achieved by introducing MuSCs into a three-dimensional (3D) bioartificial niche comprised of a thin sheet of multinucleated myotubes, which we iterate, and analyze temporally, to show that these in vivo niche features provide the minimal cues necessary to inactivate MuSCs and induce quiescence. By seeding the 3D myotube sheets with different starting numbers of MuSCs, the assay revealed cellular heterogeneity and population-level adaptation activities that converged on a common steady-state niche repopulation density; behaviors previously observed only in vivo. Quiescence-associated hallmarks included a Pax7+CalcR+MyoD- c-FOS- molecular signature, in vivo quiescent-like morphologies including oval-shaped nuclei and long cytoplasmic projections with N-cadherin+ tips, as well as the acquisition of polarized niche markers. Leveraging high-content imaging and bespoke CellProfilerTM-based image analysis pipelines, we demonstrate a relationship between morphology and cell fate signatures opening up the possibility of real-time morphology-based screening. Notably, when MuSCs from aged muscle were introduced into the assay, they displayed aberrant proliferative activities, delayed inactivation kinetics, persistence of activation-associated morphologies, and population depletion; quiescence-associated defects that we show are rescued by wortmannin treatment. Thus, the miniaturized assay offers an unprecedented opportunity to systematically investigate long-standing queries in areas such as regulation of adult stem cell pool size and functional heterogeneity within the MuSC population, and to uncover regulators of quiescence in youth and in age.

bioengineering↗

bioRxiv2022

IgD+ Age-Associated B cells are the progenitors of the main T-independent B cell response to infection that generates protective Ab and can be induced by an inactivated vaccine in the aged

Age-associated B cells (ABC) accumulate with age and are associated with autoimmunity and chronic infection. However, their contributions to acute infection in the aged and their developmental pathways are unclear. We find that the response against influenza A virus infection in aged mice is dominated by a Fas+GL7- effector B cell population we call infection-induced-ABC (iABC). Most iABC express IgM and include antibody-secreting cells in the spleen, lung and bone marrow. We find that in response to influenza, IgD+CD21-CD23-ABC are the precursors of iABC. These IgD+ABC develop in germ free mice, so are independent of foreign antigen recognition, suggesting they arise from an intrinsic age-associated developmental program. The response of ABC to influenza infection, resulting in iABC, is T cell independent and requires both extrinsic TLR7 and TLR9 signals. In response to influenza infection, IgD+ABC can induce a faster recovery of weight and higher total anti-influenza IgG and IgM titers that can neutralize virus. Immunization with whole inactivated virus also generates iABC in aged mice. Thus, in unimmunized aged mice, whose other B and T cell responses have waned, IgD+ABC are likely the naive B cells with the potential to become Ab-secreting cells and to provide protection from infection in the aged.

immunology↗

bioRxiv2022

Novel neutrophil subsets associated with sepsis, vascular dysfunction and metabolic alterations identified using systems immunology

Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Despite continued efforts to understand the pathophysiology of sepsis, no effective therapies are currently available. While singular components of the aberrant immune response have been investigated, comprehensive studies linking different data layers are lacking. Using an integrated systems immunology approach, we evaluated neutrophil phenotypes and concomitant changes in cytokines and metabolites in sepsis patients. Our findings identify novel differentially expressed immature neutrophil subsets in sepsis patients. These and other subsets correlate with various proteins, metabolites, and lipids, including pentraxin-3, angiopoietin-2 and lysophosphatidylcholines, in sepsis patients. These results enabled the construction of a predictive model based on weighted multi-omics linear regression analysis for patient classification. These findings could help inform earlier patient stratification and treatment options, as well as facilitate future mechanistic studies targeting the trifecta of surface marker expression, cytokines, and metabolites.

immunology↗

bioRxiv2022

The sowing date changed the temperature and light conditions in the field modified the cadmium content of brown rice (Oryza sativa L.) by regulating the expression of Cd-related genes

Cadmium (Cd) contamination in rice is a potential health hazard when ingested through the food chain worldwide. Reducing the Cd content in rice through agronomic measures is an effective way to reduce the risk of Cd contamination to human health. In order to clarify the correlation between temperature and light conditions and Cd accumulation (Cd-A) and Cd content of brown rice (CdBR) during the field growth period (FGP) of rice, consequently provide a theoretical basis for the selection of sowing date (SD) for "Low-Cd-Rice" production, field experiment with different SDs was carried out by using two rice varieties with different Cd accumulation characteristics (Luliangyou 996, V1, a high Cd accumulation variety; Zhuliangyou 819, V2, a low Cd accumulation variety). The results showed that the temperature and light factors such as mean soil temperature (ST), mean air temperature (AT), soil accumulation temperature (SAT), air accumulation temperature (AAT), ultraviolet radiation accumulation (UR), photosynthetic radiation accumulation (PR), light intensity accumulation (I) and sunshine hours accumulation (SH) varied to different degrees under different SDs; The difference in CdBR in two varieties could be up to 2.82 and 8.48 times respectively among SDs, with the CdBR of S4 and S5 of V2 being lower than the national standard of 0.2 mg/kg. The relative expression of OsIRT1 in the root system was significantly positively correlated with ST, SAT, AT, AAT, and SH, while OsNramp5, OsNramp1, and OsHMA3 showed significant negative correlations with ST, SAT, AT, AAT, and SH in relative expression in the root system; OsIRT1 expressed in the roots of V1 was significantly negatively correlated with CdBR, while OsHMA3 expression was significantly positively correlated with CdBR; OsLCD, OsNramp1, and OsHMA3 expression in the roots of V2 were significantly positively correlated with Cd-A and CdBR, while OsIRT1 in the roots of V2 and OsLCT1 in the leaves were significantly negatively correlated with Cd-A; The expression of OsNramp5 in roots was significantly negatively correlated with Cd-A and CdBR in both V1 and V2. Bias correlation analysis showed that ST, SAT, AT, and AAT were significantly negatively correlated with both Cd-A and CdBR; SH was significantly negatively correlated with CdBR in V1. Summarily, the temperature and light conditions during the FGP of rice and their regulation of the expression levels of related genes could be changed by sowing selection, so as to achieve safe production of rice under Cd-contaminated fields.

physiology↗

bioRxiv2021

A Drosophila Su(H) Model of Adams-Oliver Syndrome Reveals Notch Cofactor Titration as a Mechanism Underlying Developmental Defects

Notch signaling is a conserved pathway that converts extracellular receptor-ligand interactions into changes in gene expression via a single transcription factor (CBF1/RBPJ in mammals; Su(H) in Drosophila). In humans, RBPJ variants have been linked to Adams-Oliver syndrome (AOS), a rare autosomal dominant disorder characterized by scalp, cranium, and limb defects. Here, we found that a previously described Drosophila Su(H) allele encodes a missense mutation that alters an analogous residue found in an AOS-associated RBPJ variant. Importantly, genetic studies support a model that Drosophila with a single copy of the AOS-like Su(H) allele behave in an opposing manner as flies with a Su(H) null allele due to a dominant activity of sequestering either the Notch co-activator or the antagonistic Hairless co-repressor. Consistent with this model, AOS-like Su(H) and Rbpj variants decrease DNA binding activity compared to wild type proteins, but these variants do not significantly alter protein binding to the Notch co-activator or the fly and mammalian co-repressors, respectively. Taken together, these data suggest a cofactor sequestration mechanism underlies AOS phenotypes associated with RBPJ variants, whereby a single RBPJ allele encodes a protein with compromised DNA binding activity that retains cofactor binding, resulting in Notch target gene dysregulation.

genetics↗