Biology subjects

Xu, G.

Publications and source records attributed to Xu, G..

At least 55 records · Page 3Linked to original sources

bioRxiv2025

ND-13, a DJ-1 derived peptide, as a novel pharmacological approach in the prevention of NLRP3 inflammasome activity in Diabetic Nephropathy

Diabetic nephropathy is the most important cause of renal failure worldwide and is characterized by sustained inflammation regulated in part by NLRP3 Inflammasome. Attenuation of inflammation is a major priority to prevent renal damage. Our previous publications show that DJ-1 has antioxidant and anti-inflammatory properties in the kidney. ND-13 is a short peptide consisting of 13 amino acids of the DJ-1-protein, which could increase DJ-1 pathway activation. The aim of these studies was to determine the role of NLRP3 in the pathogenesis of diabetic nephropathy and to study the possible renal protective effects of the DJ-1 pathway in diabetic mice and on inflammasome regulation. Bone marrow derived macrophages were treated with ND-13 and cultivated in high and low glucose. Diabetes was induced in C57Bl/6 mice via injection of streptozotocin and treated with ND-13 and MCC950, an inhibitor of the NLRP3 inflammasome. Peripheral mononuclear cells were isolated from human with diabetes, diabetic nephropathy and healthy donors and were plated, pretreated with ND-13 and stimulated with LPS+ATP. IL-1{beta} concentration in the medium of bone marrow derived macrophages increased by NLRP3 inflammasome stimulation by LPS+ATP, and decreased in macrophages pre-treated with ND-13, however, in the presence of LPS+Nigericin no effect was found. Peritoneal macrophages from diabetic mice were obtained and plated. Streptozotocin-induced diabetic C57BL/6 mice have increased the peritoneal cells IL-1{beta} production compared with control mice, suggesting that inflammasome may be activated in macrophages during diabetes and that ND-13 treatment normalized its activity. ND-13 and MCC950 decreased histologic evidence of tubular injury in STZ-induced diabetes in mice, additionally, significantly increased the mRNA expression of Col-I, Col-II, Tgf-{beta}, Il-6, Tnf- and P2x7 in the renal cortex, which was partially prevented by ND-13 and MCC950 pre-treatment. P2x7 mRNA expression was also increased in peritoneal macrophages obtained from diabetic mice, and its expression was attenuated by ND-13 pre-treatment. Peripheral mononuclear cells isolated from patients blood were plated and stimulated with LPS+ATP. Patients with diabetic nephropathy presented a significant increase of IL-1{beta} release compared to diabetic individuals and ND-13 could has a role in the prevention of inflammasome activation in healthy patients. Our results demonstrate that activation of the DJ-1 pathway is a promising approach to prevent renal inflammation and fibrosis during diabetes, by ameliorating inflammasome activation in peripheral immune cells. Thus, ND-13 could be a promising new therapeutic approach to attenuating inflammation and renal damage in diabetic nephropathy.

cell biology↗

bioRxiv2024

Characterizing Tyrosine Ring Flips in Proteins by 19F NMR

Aromatic ring-flip dynamics are hallmarks of concerted protein "breathing" motions that are essential for biological function. Ring flips occur on a broad range of timescales (ns-s) and have been primarily studied by NMR spectroscopy, typically requiring expensive isotope labeling of aromatic side chains, thereby limiting such studies to a few proteins. Here, we report two novel di-fluorotyrosine probes, 3,5-F2Y and 2,6-F2Y, that can be incorporated into proteins cost-effectively for characterizing and modulating tyrosine ring-flip dynamics. We show that 19F rotating-frame (R1{rho}) relaxation dispersion is powerful for quantifying ring flips on the {micro}s-ms timescale. Importantly, the tyrosine ring-flip rates (kflip) for 3,5-F2Y in GB1 and HPr are comparable to those measured by 1H and 13C NMR studies, validating 3,5-F2Y as a largely non-perturbing, native-like ring-flip probe. In contrast, 2,6-F2Y acts as an effective "brake" on ring flips, enabling direct visualization and quantitative characterization of previously undetected tyrosine ring flips in ubiquitin via 19F lineshape analysis. Furthermore, we use 2,6-F2Y to assess the environmental effects on ring-flip dynamics in crowding reagents and in living X. laevis oocytes. Collectively, our study opens a new avenue for measuring and modulating ring-flip dynamics in vitro and in living cells. TOC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=165 SRC="FIGDIR/small/630691v2_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@dcf8e1org.highwire.dtl.DTLVardef@1578887org.highwire.dtl.DTLVardef@1c481d0org.highwire.dtl.DTLVardef@268ae0_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2024

OPUS-GO: An interpretable protein/RNA sequence annotation framework based on biological language model

Accurate annotation of protein and RNA sequences is essential for understanding their structural and functional attributes. However, due to the relative ease of obtaining whole sequence-level annotations compared to residue-level annotations, existing biological language model (BLM)-based methods often prioritize enhancing sequence-level classification accuracy while neglecting residue-level interpretability. To address this, we introduce OPUS-GO, which exclusively utilizes sequence-level annotations to provide both sequence-level and residue-level classification results. In other words, OPUS-GO not only provides the sequence-level annotations but also offers the rationale behind these predictions by pinpointing their corresponding most critical residues within the sequence. Our results show that, by leveraging features derived from BLMs and our modified Multiple Instance Learning (MIL) strategy, OPUS-GO exhibits superior sequence-level classification accuracy compared to baseline methods in most downstream tasks. Furthermore, OPUS-GO demonstrates robust interpretability by accurately identifying the residues associated with the corresponding labels. Additionally, the OPUS-GO framework can be seamlessly integrated into any language model, enhancing both accuracy and interpretability for their downstream tasks.

bioinformatics↗

bioRxiv2024

Targeted degradation of endogenous condensation-prone proteins improves crop performance

Effective methods, such as CRISPR and RNA interference, exist for modulating gene expression at DNA and RNA levels, but approaches for directly modifying endogenous proteins remain lacking in plants. Here, we develop a targeted condensation-prone-protein degradation (TCD) strategy to eliminate endogenous proteins, particularly those prone to condensation. We identify an E3 ligase, E3TCD1, that degrades itself but selectively targets other proteins when fused to them. In rice, transgenic E3TCD1 fusions with Teosinte branched 1 and Early flowering 3 (OsELF3) modulate tiller numbers and flowering times, respectively. The TCD system is also controllable. Using the ProTBF1-uORFsTBF1 expression control cassette, we can conditionally degrade the negative defense regulator OsELF3 upon pathogen invasion, enhancing rice resistance without interfering with rice flowering time. This method, unlike animal-targeting strategies, does not rely on small molecules, antibodies, or genetic knock-ins, showing promise as a gene therapeutic avenue for optimizing crop performance and potentially addressing human diseases.

plant biology↗

bioRxiv2024

A combinatorial approach to ALS therapies in the PrP.TDP43-315 model of ALS; complications and tribulations

Effective treatment for sporadic amyotrophic lateral sclerosis has been steadily advancing towards combinatorial therapies. For many years, riluzole was the only approved drug and it offered modest benefits. In 2017, edaravone was approved for ALS and became the first drug to be used in combination with riluzole. In the present study, we have attempted to build on the concepts of combinatorial therapy by testing novel drug combinations in a transgenic mouse model. Mice that express A315T mutant TDP43, using the mouse prion promoter, have been reported to develop many of the symptoms of ALS, including paralysis. Aberrant TDP43 function is a common feature in sporadic ALS, and thus TDP43 transgenic models may recapitulate disease processes that occur in humans with sporadic ALS. Although the PrP.TDP43-A315T model has been reported to develop abnormalities in gut motility that contribute to early mortality, recent studies indicated that gut motility issues could be mitigated by feeding mice with gel-based diets rather than the standard dry chow. In the present study, we have attempted to use the PrP.TDP43-A315T model to test whether we could identify a drug combination that synergized to extend life span in this model substantially. The drug combinations were built around the existing drug modalities, adding additional drugs that had indications of utility from the literature. To mitigate gut motility issues, we fed the mice gel-based diets with or without added drug combinations. Although the gel-based diets extended life expectancy in PrP.TDP43-A315T mice, most of the animals still developed gut motility abnormalities that may have contributed to early mortality. None of the drug combinations we tested extended life expectancy in this model substantially.

neuroscience↗

bioRxiv2024

Making Aptamers More Antibody-like: Targeting AXL in Vivo Using a Bottlebrush Polymer-Conjugated Aptamer

The overexpression of receptor tyrosine kinase AXL is linked to acquired drug resistance in cancer treatments. Aptamers, acting as antibody surrogates, have been envisioned as potential inhibitors for AXL. However, aptamers face difficult pharmacological challenges including rapid degradation and clearance. Herein, we report a phosphodiester-backboned bottlebrush polymer as a carrier for conjugated aptamers. Termed pacDNA, the conjugate improves aptamer specificity in vivo, prolongs blood retention, and enhances overall aptamer bioactivity. Treatment with pacDNA in AXL-overexpressing cell lines significantly inhibits AXL phosphorylation, resulting in reduced cancer cell migration and invasion. In a non-small cell lung cancer xenograft model (NCI-H1299), pacDNA treatment leads to single-agent reduction in tumor growth. These results highlight the potential of bottlebrush polymers in the field of aptamer therapeutics.

cancer biology↗

bioRxiv2024

The conversion of forests to agricultural land reduced the content of soil black carbon fractions in a karst rocky desertification area of Southwest China

Understanding the effects of land use on soil black carbon (BC) is critical for correctly interpreting the role of BC in the carbon cycle of karst areas. This study investigated the distribution characteristics of organic carbon (OC), BC, char, and soot and soil physicochemical properties of the soil profiles (0-40 cm) of secondary forest, shrub, farmland, and wasteland in a rocky desertification area of Guangxi Province, a typical karst rocky desertification area in Southwest China. We used a combination of soot/char and {delta}13CBC isotope analysis to identify the source of BC of these soils. The average value of soil BC was the highest in secondary forest, followed by shrub, farmland, and wasteland in the 0-40 cm soil layer. BC had a positive correlation with OC, char, soot,soil nitrogen, phosphorus and potassium, showed a negative correlation with bulk density. In the black carbon component, char occupies a greater proportion than soot, with the heavy fraction OC exhibiting a higher concentration of BC than the light fraction OC. Conclusively, the BC content was mainly due to C3 plant burning, vehicle exhaust emissions, and fossil fuel utilization.Vegetation restoration improved the soil BC content associated with OC sequestration in the typical karst rocky desertification mountainous area of Southwest Guangxi.

ecology↗

bioRxiv2024

Effects of Inosine-5'-Monophosphate Dehydrogenase (IMPDH/GuaB) Inhibitors on Borrelia burgdorferi Growth in Standard and Modified Culture Conditions

Borrelia burgdorferis Inosine-5-Monophosphate dehydrogenase (IMPDH, GuaB) is a potential therapeutic target. GuaB is not needed for B. burgdorferi survival and replication in standard growth media, therefore our ability to test novel drugs against the whole organism is limited to tests using mammalian hosts. Modifications to standard culture conditions that can induce borreliastatic effects of GuaB inhibitors will enhance our ability to evaluate these inhibitors. This study aimed to evaluate basic modifications to standard growth media that can achieve this objective. Effects of GuaB inhibitors (mycophenolic acid, 6-Chloropurine) were compared in standard Barbour-Stoenner-Kelly-II (BSK-II) medium with BSK-II modified to 60% concentration rabbit serum, using B. burgdorferi 5A1. Effects were also evaluated with another BSK-II modification with the direct supplementation of hypoxanthine, adenine, and nicotinamide (75 M each). In standard BSK-II, neither mycophenolic acid nor 6-Chloropurine riboside affected B. burgdorferi growth. An ANOVA showed significant, dose-dependent interactions between culture condition and treatment considering modified growth conditions (F = 4.471, P = 0.001). Mycophenolic acid at 250 M reduced replication by 48 and 50% (P < 0.001 each). 6-Chloropurine riboside was more effective in both conditions at 250 M, reducing growth by 64 and 65% (P < 0.001 each). Effects of GuaB inhibitors were shown against whole organism Borrelia burgdorferi for the first time. Modification of BSK-II medium with physiologically relevant levels of mammalian serum supports replication and induces GuaB inhibitor-mediated suppression of replication. Effects of 6-Chloropurine riboside were demonstrated for the first time, indicating that B. burgdorferi can salvage and phosphorylate these analogue purine derivatives. These molecules can be manipulated to better inhibit replication. Optimisation will allow the assessment of novel Borrelia-specific IMPDH inhibitor molecules in culture for Lyme disease interventions. HighlightsO_LIEffects of IMPDH inhibitors are shown against whole organism Borrelia burgdorferi for the first time. C_LIO_LIModification of BSK-II medium with physiologically relevant levels of mammalian serum supports replication and induces IMPDH inhibitor-mediated suppression of replication. C_LIO_LIEffects of 6-Chloropurine riboside are demonstrated for the first time, indicating that B. burgdorferi can salvage and phosphorylate these analogue purine derivatives. These molecules can be manipulated to better inhibit replication. C_LIO_LIOptimisation of modified BSK-II will allow the assessment of novel Borrelia-specific IMPDH inhibitor molecules in culture for Lyme disease interventions. C_LI

microbiology↗

bioRxiv2024

ProtRNA: A Protein-derived RNA Language Model by Cross-Modality Transfer Learning

Protein language models (PLM), such as the highly successful ESM-2, have proven particularly effective. However, language models designed for RNA continue to face challenges. A key question is: can the information derived from PLMs be harnessed and transferred to RNA? To investigate this, a model termed ProtRNA has been developed by cross-modality transfer learning strategy for addressing the challenges posed by RNAs limited and less conserved sequences. By leveraging the evolutionary and physicochemical information encoded in protein sequences, the ESM-2 model is adapted to processing "low-resource" RNA sequence data. The results show comparable or superior performance in various RNA downstream tasks, with only 1/8 the trainable parameters and 1/6 the training data employed by the primary reference baseline RNA language model. This approach highlights the potential of cross-modality transfer learning in biological language models.

bioinformatics↗

bioRxiv2024

OPUS-Design: Designing Protein Sequence from Backbone Structure with 3DCNN and Protein Language Model

Protein sequence design, also known as protein inverse folding, is a crucial task in protein engineering and design. Despite the recent advancements in this field, which have facilitated the identification of amino acid sequences based on backbone structures, achieving higher levels of accuracy in sequence recovery rates remains challenging. It this study, we introduce a two-stage protein sequence design method named OPUS-Design. Our evaluation on recently released targets from CAMEO and CASP15 shows that OPUS-Design significantly surpasses several other leading methods on both monomer and oligomer targets in terms of sequence recovery rate. Furthermore, by utilizing its finetune version OPUS-Design-ft and our previous work OPUS-Mut, we have successfully designed a thermal-tolerant double-point mutant of T4 lysozyme that demonstrates a residual enzyme activity exceeding that of the wild-type T4 by more than twofold when both are subjected to extreme heat treatment at 70{degrees}C. Importantly, this accomplishment is achieved through the experimental verification of less than 10 mutant candidates, thus significantly alleviating the burden of experimental verification process.

bioengineering↗

bioRxiv2024

OPUS-BFactor: Predicting protein B-factor with sequence and structure information

Protein B-factor, also known as the Debye-Waller factor, measures the fluctuation of an atom around its average position. It serves as a crucial indicator of protein flexibility and dynamics. However, accurately predicting the B-factor of C atoms remains challenging. In this work, we introduce OPUS-BFactor, a tool for predicting the normalized protein B-factor. OPUS-BFactor operates in two modes: the first mode, OPUS-BFactor-seq, uses sequence information as input, allowing predictions based solely on protein sequence; the second mode, OPUS-BFactor-struct, uses structural information, requiring the 3D structure of the target protein. Evaluation on three test sets, including recently released targets from CAMEO and CASP15, demonstrates that OPUS-BFactor significantly outperforms other B-factor prediction methods. Therefore, OPUS-BFactor is a valuable tool for predicting protein properties related to the B-factor, such as flexibility, thermal stability, and region activity.

bioinformatics↗

bioRxiv2024

Somy evolution in the honey bee infecting trypanosomatid parasite, Lotmaria passim

Lotmaria passim is a ubiquitous trypanosomatid parasite of honey bees nestled within the medically important subfamily Leishmaniinae. Although this parasite is associated with honey bee colony losses, the original draft genome--which was completed before its differentiation from the closely related Crithidia mellificae--has remained the reference for this species despite lacking improvements from newer methodologies. Here we report the updated sequencing, assembly, and annotation of the BRL type strain (ATCC PRA-422) of Lotmaria passim. The nuclear genome assembly has been resolved into 31 complete chromosomes and is paired with an assembled kinetoplast genome consisting of a maxicircle and 30 minicircle sequences. The assembly spans 33.7 Mb and contains very little repetitive content, from which our annotation of both the nuclear assembly and kinetoplast predicted 10,288 protein-coding genes. Analyses of the assembly revealed evidence of a recent chromosomal duplication event within chromosomes 5 and 6 and provides evidence for a high level of aneuploidy in this species, mirroring the genomic flexibility employed by other trypanosomatids as a means of adaptation to different environments. This high-quality reference can therefore provide insights into adaptations of trypanosomatids to the thermally regulated, acidic, and phytochemically rich honey bee hindgut niche, which offers parallels to the challenges faced by other Leishmaniinae during the challenges they undergo within insect vectors, during infection of mammals, and exposure to antiparasitic drugs throughout their multi-host life cycles. This reference will also facilitate investigations of strain-specific genomic polymorphisms, their role in pathogenicity, and the development of treatments for pollinator infection.

genomics↗

bioRxiv2024

Exploring the therapeutic potential of a novel series of imidazothiadiazoles targeting focal adhesion kinase (FAK) for pancreatic cancer treatment: Synthesis, mechanistic Insights and promising antitumor and safety profile

Focal Adhesion Kinase (FAK) is a non-receptor protein tyrosine kinase that plays a crucial role in various oncogenic processes related to cell adhesion, migration, proliferation, and survival. The strategic targeting of FAK represents a burgeoning approach to address resistant tumors, such as pancreatic ductal adenocarcinoma (PDAC). Herein, we report a new series of twenty imidazo[2,1-b][1,3,4]thiadiazole derivatives assayed for their antiproliferative activity against the National Cancer Institute (NCI-60) panel and a wide panel of PDAC models. Lead compound 10l exhibited effective antiproliferative activity against immortalized (SUIT-2, CAPAN-1, PANC-1, PATU-T, BxPC-3), primary (PDAC-3) and gemcitabine-resistant clone (PANC-1-GR) PDAC cells, eliciting IC50 values in the low micromolar range (1.04-3.44 {micro}M), associated with a significant reduction in cell-migration and spheroid shrinkage in vitro. High-throughput kinase arrays revealed a significant inhibition of the FAK signalling network, associated to induction of cell cycle arrest in G2/M phase, suppression of tumor cell invasion and apoptosis induction. The low selectivity index/toxicity prompted studies using PDAC mouse xenografts, demonstrating significant inhibition of tumor growth and safety. In conclusion, compound 10l displayed antitumor activity and safety in both in vitro and in vivo models, emerging as a highly promising lead for the development of FAK inhibitors in PDAC.

cancer biology↗

bioRxiv2024

Human APOE allelic variants suppress the formation of diffuse and fibrillar Aβ deposits relative to mouse Apoe in transgenic mouse models of Alzheimer amyloidosis

BackgroundApolipoprotein E (apoE) modulates the deposition of amyloid {beta} (A{beta}) aggregates in Alzheimers disease (AD) in an isoform-dependent manner. In transgenic mouse models of AD-amyloidosis, replacing mouse Apoe alleles with human APOE variants suppresses fibrillar A{beta} deposits. In the PD-APP transgenic mouse model, deletion of the Apoe gene led to selective reduction of fibrillar deposits with increased diffuse deposits. This finding suggested that apoE may have differential effects on different types of amyloid pathology. MethodsHere, we investigated the interaction between the type of A{beta} pathology in the brain and human apoE isoforms in different transgenic mouse models. ResultsIn the APPsi model that develops predominantly diffuse A{beta} plaques late in life, we determined that replacing mouse Apoe with human APOE3 or APOE4 genes potently suppressed diffuse amyloid formation, with apoE3 exhibiting a greater activity relative to apoE4. Relative to apoE4, apoE3 appeared to suppress A{beta} deposition in the cerebral vasculature. In a second cohort, we accelerated the deposition of diffuse A{beta} pathology by seeding, finding that seeded APPsi mice harboring APOE4 or APOE3 developed equal burdens of diffuse parenchymal A{beta}. Finally, in the recently developed SAA-APP model that has a mix of dense-core and fibrous A{beta} plaques, we found that replacing mouse apoE with human apoE suppressed deposition significantly, with the amyloid burden following the trend of Apoe>>APOE4> APOE3[~]APOE2. In the SAA-APP and seeded APPsi models, we found evidence of apoE protein associated with A{beta} plaques. ConclusionsOverall, these observations demonstrate a capacity for human apoE to suppress the deposition of both diffuse and fibrillar-cored deposits, relative to mouse apoE. Notably, in the seeded paradigm, the suppressive activity of human apoE3 and apoE4 appeared to be overwhelmed. Taken together, this study demonstrates that APOE genotype influences the deposition of both cored-fibrillar and diffuse amyloid.

neuroscience↗

bioRxiv2024

Mechano-regulation of GLP-1 production by Piezo1 in intestinal L cells

Glucagon-like peptide 1 (GLP-1) is a gut-derived hormone secreted by intestinal L cells and vital for postprandial glycemic control. As open-type enteroendocrine cells, whether L cells can sense mechanical stimuli caused by chyme and thus regulate GLP-1 synthesis and secretion is unexplored. Our study showed expression of Piezo1 in intestinal L cells. Its level varied in different energy status and correlates with blood glucose and GLP-1 levels. Mice with L cell-specific loss of Piezo1 (IntL-Piezo1-/-) exhibited impaired glucose tolerance, increased body weight, reduced GLP-1 production and decreased CaMKK{beta}/CaMKIV-mTORC1 signaling pathway under normal chow diet or high fed diet. Activation of the intestinal Piezo1 by its agonist Yoda1 or intestinal bead implantation increased the synthesis and secretion of GLP-1, thus alleviated glucose intolerance in diet-induced-diabetic mice. Overexpression of Piezo1, Yoda1 treatment or stretching stimulated GLP-1 production and CaMKK{beta}/CaMKIV-mTORC1 signaling pathway, which could be abolished by knockdown or blockage of Piezo1 in primary cultured mouse L cells and STC-1 cells. These findings suggest a previously undiscovered mechano-regulation of GLP-1 production in L cells, which may shed new light on the treatments of diabetes.

physiology↗

bioRxiv2024

In-depth investigation of the mechanisms of high and low residual feed intake regulating hens during the late laying period via liver and gut microbiota.

Residual feed intake (RFI) is a more accurate indicator of feed efficiency than the feed conversion ratio (FCR) and is widely used to measure the efficiency of livestock and poultry feed utilization. Typically, Low RFI (LRFI) implies higher feed conversion efficiency, while high RFI (HRFI) indicates lower feed conversion efficiency. This study systematically explored the differences between high and low RFI and the function of the liver and cecum microbes of hens during the late laying period by multiple-omics techniques and further explored the interaction among microorganisms, the function of tissues and organs, and body metabolism. The results showed that the length and mass of the digestive organs in the LRFI group were higher than those in the HRFI group as well as the chest width. Additionally, the key genes and metabolites regulating RFI in hens during the late laying phase were found to be ADCY2, ADCY8, CCKAR, ACSS2, FABP1, FABP4, and LysoPI (18:2(9Z,12Z)/0:0) in the liver. The levels of AST, HDL-C and ACTH in the serum were considered candidate markers influencing RFI. By conducting a microbiome-metabolome association analysis, we have identified the dominant and beneficial microbial community in the gut of LRFI groups, such as Oscillospirales, Ruminococcaceae, and Butyricicoccaceae, which offers a theoretical basis for understanding how the gut microbiota regulates RFI. These results will provide a scientific basis for the molecular mechanism of RFI phenotypic variation in late laying hens.

microbiology↗

bioRxiv2024

Cancer Stemness Online: A resource for investigating cancer stemness and associations with immune response

Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features, which are potential culprit in immunotherapy resistance. Although the state-of-art predictive computational methods have facilitated predicting the cancer stemness, currently there is no efficient resource that can meet various requirements of usage. Here, we presented the Cancer Stemness Online, an integrated resource for efficiently scoring cancer stemness potential at bulk and single-cell level. The resource integrates 8 robust predictive algorithms as well as 27 signature gene sets associated with cancer stemness for predicting the stemness scores. Downstream analyses were performed from five different aspects, including identifying the signature genes of cancer stemness, exploring the association with cancer hallmarks, cellular states, immune response and communication with immune cells, investigating the contributions for patient survival and the robustness analysis of cancer stemness among different methods. Moreover, the pre-calculated cancer stemness atlas for more than 40 cancer types can be accessed by users. Both the tables and diverse visualization for the analytical results are available for download. Together, Cancer Stemness Online is a powerful resource for scoring cancer stemness and going deeper and wider in the downstream functional interpretation, including immune response as well as cancer hallmark. Cancer Stemness Online is freely accessible at http://bio-bigdata.hrbmu.edu.cn/CancerStemnessOnline.

bioinformatics↗

bioRxiv2024

SHOOTMERISTEMLESS autoactivation: A prerequisite for fruit metamorphosis

In animals and plants, organ shape is primarily determined during primordium development by carefully coordinated growth and cell division1-3. Rare examples of post-primordial change in morphology (reshaping) exist that offer tractable systems to study mechanisms required for organ-shape determination and diversification. One such example is the heart-shape formation of Capsella fruits that occurs by reshaping the ovate spheroid gynoecium upon fertilization4. Here we use whole-organ live-imaging to show that dynamic changes in growth and cell division coupled with local maintenance of meristematic identity drives Capsella fruit-shape formation. At the molecular level, we reveal an auxin-induced mechanism ultimately descending on a single cis regulatory element to mediate morphological alteration. This element resides in the promoter of the Capsella rubella SHOOTMERISTEMLESS5 (CrSTM) gene. The CrSTM meristem identity factor positively regulates its own expression through binding to this element thereby providing a feed-forward loop at the position and time when protrusions emerge to form the heart. Independent evolution of the STM-binding element in STM promoters across Brassicaceae species correlates with those undergoing a gynoecium-to-fruit metamorphosis. Accordingly, genetic and phenotypic studies showed that the STM-binding element is required to facilitate the shape transition and reveals a conserved molecular mechanism for organ morphogenesis.

plant biology↗