RESUMEN
Studying the biogeographic patterns of fungal communities across altitudinal and soil depth gradients is essential for understanding how environmental variations shape the diversity and functionality of these complex ecological assemblages. Here, we evaluated the response and assembly patterns of fungal communities to altitude and soil depth, and the co-occurrence patterns influencing soil fungal metabolic preferences on Dongling Mountain. We observed significant variations in fungal ß-diversity, driven by elevation and soil depth, with climatic parameters (MAT and MAP) and nutrient concentrations (TOC, TP, and TN) serving as prominent influencers. Additionally, we found that the multiple substrate-induced respiration rate of fungi degrading various carbon substrates was diminished in high-altitude and subsurface soils compared to low-altitude and surface soils. Stochastic processes play a more important role in controlling fungal community assembly than deterministic processes, with dispersal limitation emerging as the main driver of community assembly. While greater network complexity was evident in the topsoil compared to the subsoil, both layers harbored altitude-sensitive OTUs (asOTUs) that belonging to distinct modules. Moreover, fungal groups sensitive to the same altitude exhibited similar metabolic preferences. The asOTUs designated for lower altitude areas favored unstable carbon substrates (glucose and sucrose), while those designated as higher altitude areas exhibited a preference for recalcitrant carbon (xylan and lignin). This evidence suggests that soil fungal communities respond to environmental changes by trading off their life strategies and metabolic characteristics.
Asunto(s)
Altitud , Hongos , Microbiología del Suelo , Suelo , Suelo/química , Micobioma , ChinaRESUMEN
Photochemical internalization is an efficient strategy relying on photodynamic reactions to promote siRNA endosomal escape for the success of RNA-interference gene regulation, which makes gene-photodynamic combined therapy highly synergistic and efficient. However, it is still desired to explore capable carriers to improve the delivery efficiency of the immiscible siRNA and organic photosensitizers simultaneously. Herein, we employ a micellar nanostructure (PSNA) self-assembled from polymer-DNA molecular chimeras to fulfill this task. PSNA can plentifully load photosensitizers in its hydrophobic core simply by the nanoprecipitation method. Moreover, it can organize siRNA self-assembly by the densely packed DNA shell, which leads to a higher loading capacity than the typical electrostatic condensation method. The experimental results prove that this PSNA carrier can greatly facilitate siRNA escape from the endosome/lysosome and enhance transfection. Accordingly, the PSNA-administrated therapy exhibits a significantly improved anti-tumor efficacy owing to the highly efficient co-delivery capability.
Asunto(s)
ADN , Fotoquimioterapia , Fármacos Fotosensibilizantes , Polímeros , ARN Interferente Pequeño , Transfección , ARN Interferente Pequeño/química , ARN Interferente Pequeño/metabolismo , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , ADN/química , Humanos , Polímeros/química , Luz , Portadores de Fármacos/química , AnimalesRESUMEN
Manipulation of the lactate metabolism is an efficient way for cancer treatment given its involvement in cancer development, metastasis, and immune escape. However, most of the inhibitors of lactate transport carriers suffer from poor specificity. Herein, we use the CRISPR/Cas9 system to precisely downregulate the monocarboxylate carrier 1 (MCT1) expression. To avoid the self-repairing during the gene editing process, a dual-Cas9 ribonucleoproteins (duRNPs) system is generated using the biological fermentation method and delivered into cells by the zeolitic imidazolate framework-8 (ZIF-8) nanoparticles, enabling precise removal of a specific DNA fragment from the genome. For efficient cancer therapy, a specific glucose transporter 1 inhibitor (BAY-876) is co-delivered with the duRNPs, forming BAY/duRNPs@ZIF-8 nanoparticle. ZIF-8 nanoparticles can deliver the duRNPs into cells within 1 h, which efficiently downregulates the MCT1 expression, and prohibits lactate influx. Through simultaneous inhibition of the lactate and glucose influx, BAY/duRNPs@ZIF-8 prohibits ATP generation, arrests cell cycle, inhibits cell proliferation, and finally induces cellular apoptosis both in vitro and in vivo. Consequently, we demonstrate that the biologically produced duRNPs delivered into cells by the nonviral ZIF-8 carrier have expanded the CRISPR/Cas gene editing toolbox and elevated the gene editing efficiency, which will promote biological studies and clinical applications. STATEMENT OF SIGNIFICANCE: The CRISPR/Cas9 system, widely used as an efficient gene editing tool, faces a challenge due to cells' ability to self-repair. To address this issue, a strategy involving dual-cutting of the genome DNA has been designed and implemented. This strategy utilizes biologically produced dual-ribonucleoproteins delivered by a metal-organic framework. The effectiveness of this dual-cut CRISPR-Cas9 system has been demonstrated through a therapeutic approach targeting the simultaneous inhibition of lactate and glucose influx in cancer cells. The utilization of the dual-cut gene editing strategy has provided valuable insights into gene editing and expanded the toolbox of the CRISPR/Cas-based gene editing system. It has the potential to enable more efficient and precise manipulation of specific protein expression in the future.
Asunto(s)
Estructuras Metalorgánicas , Neoplasias , Edición Génica/métodos , Sistemas CRISPR-Cas/genética , ADN , Ribonucleoproteínas/genética , Lactatos , Glucosa , Neoplasias/genética , Neoplasias/terapiaRESUMEN
Soil bacterial communities are essential for ecosystem function, yet their response along altitudinal gradients in different soil strata remains unclear. Understanding bacterial community co-occurrence networks and assembly patterns in mountain ecosystems is crucial for comprehending microbial ecosystem functions. We utilized Illumina MiSeq sequencing to study bacterial diversity and assembly patterns of surface and subsurface soils across a range of elevations (700 to 2100 m) on Dongling Mountain. Our results showed significant altitudinal distribution patterns concerning bacterial diversity and structure in the surface soil. The bacterial diversity exhibited a consistent decrease, while specific taxa demonstrated unique patterns along the altitudinal gradient. However, no altitudinal dependence was observed for bacterial diversity and community structure in the subsurface soil. Additionally, a shift in bacterial ecological groups is evident with changing soil depth. Copiotrophic taxa thrive in surface soils characterized by higher carbon and nutrient content, while oligotrophic taxa dominate in subsurface soils with more limited resources. Bacterial community characteristics exhibited strong correlations with soil organic carbon in both soil layers, followed by pH in the surface soil and soil moisture in the subsurface soil. With increasing depth, there is an observable increase in taxa-taxa interaction complexity and network structure within bacterial communities. The surface soil exhibits greater sensitivity to environmental perturbations, leading to increased modularity and an abundance of positive relationships in its community networks compared to the subsurface soil. Furthermore, the bacterial community at different depths was influenced by combining deterministic and stochastic processes, with stochasticity (homogenizing dispersal and undominated) decreasing and determinism (heterogeneous selection) increasing with soil depth.
Asunto(s)
Ecosistema , Suelo , Suelo/química , Carbono , Microbiología del Suelo , Bosques , Bacterias , ChinaRESUMEN
NIR-II fluorescence imaging-guided photothermal therapy (PTT) has been widely investigated due to its great application potential in tumor theranostics. PTT is an effective and non-invasive tumor treatment method that can adapt to tumor hypoxia; nevertheless, simple and effective strategies are still desired to develop new materials with excellent PTT properties to meet clinical requirements. In this work, we developed a bromine-substitution strategy to enhance the PTT of A-D-A'-D-A π-conjugated molecules. The experimental results reveal that bromine substitution can notably enhance the absorptivity (ϵ) and photothermal conversion efficiency (PCE) of the π-conjugated molecules, resulting in the brominated molecules generating two times more heat (ϵ808â nm ×PCE) than their unsubstituted counterpart. We disclose that the enhanced photothermal properties of bromine-substituted π-conjugated molecules are a combined outcome of the heavy-atom effect, enhanced ICT effect, and more intense bromine-mediate intermolecular π-π stacking. Finally, the NIR-II tumor imaging capability and efficient PTT tumor ablation of the brominated π-conjugated materials demonstrate that bromine substitution is a promising strategy for developing future high-performance NIR-II imaging-guided PTT agents.
Asunto(s)
Nanopartículas , Neoplasias , Humanos , Fototerapia , Bromo/uso terapéutico , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Terapia Fototérmica , Línea Celular Tumoral , Nanomedicina Teranóstica/métodosRESUMEN
Soil bacterial and fungal community communities play significant ecological functions in mountain ecosystems. However, it is not clear how topographic factors and soil physicochemical properties influence changes in microbial community structure and diversity. This study aims to investigate how altitude and slope orientation affect soil physicochemical properties, soil microbial communities, and their contributing factors. The assessment was conducted using Illumina MiSeq sequencing in various altitude gradients and on slopes with different aspects (shady slopes and sunny slopes) in the subalpine meadow of Dongling Mountain, Beijing. Topographical factors had a significant effect on soil physicochemical properties: the primary factors determining the structure of microbial communities are total potassium (TK), ammonium nitrogen (NH4+-N), and soil organic carbon (SOC). There was no significant change in the diversity of the bacterial community, whereas the diversity of the fungal community displayed a single-peaked trend. The effect of slope orientation on microbial communities was not as significant as the effect of elevation on them. The number of bacterial communities with significant differences showed a unimodal trend, while the number of fungal communities showed a decreasing trend. The co-occurrence network of fungal communities exhibits greater intricacy than that of bacterial communities, and bacterial communities are more complex in soils with sunny slopes compared to soils with shady slopes, and the opposite is true for fungal communities. The identification of the main factors that control soil microbial diversity and composition in this study, provided the groundwork for investigating the soil microbial response and adaptation to environmental changes in subalpine meadows.
RESUMEN
The H3-subtype of avian influenza virus (AIV) is one of the most frequently detected low pathogenic avian influenza virus (LPAIV) subtypes in birds and fowls, causing substantial economic loss to the poultry industry. Most importantly, besides poultry, mammals could also be infected with it, such as swines, canines, equines, felines, and humans, posing a serious public health threat. This allows the virus to persist widely in poultry and wild birds for a long time, where it may mix with other subtypes, providing conditions for viral recombination or reassortment. Currently, the monitoring of H3-subtype AIV is inadequate, and there is a lack of effective prevention and control measures for H3-subtype AIV. Here, the epidemiology, phylogeny, and genetic variation of H3-subtype AIV were analyzed, and nonsynonymous and synonymous substitution rates (dN/dS) were calculated. Through these steps, we aimed to clarify the current epidemiological feature and evolutionary characteristics of H3-subtype AIV, and provide an operative reference for future scientific control of H3-subtype AIV.
RESUMEN
Metal-organic frameworks (MOFs) with periodically arranged porphyrinic linkers avoiding the self-quenching issue of porphyrins in photodynamic therapy (PDT) have been widely applied. However, the porphyrinic MOFs still face challenges of poor stability under physiological conditions and limited photodynamic efficiency by the hypoxia condition of tumors. Herein, we fabricate the MOF@MOF structure with a protective MOF shell to improve the stability and relieve the hypoxia condition of tumors for sensitized PDT. Under protection of the MOF shell, the MOF@MOF structure can keep intact for 96 h under physiological conditions. Consequently, the tumoral accumulation efficiency is two folds of the MOF core. Furthermore, the MOF shell decomposes under acidic environment, and the loaded inhibitor of mitochondria pyruvate carrier (7-amino carboxycoumarins-2, 7ACC2) will be released. 7ACC2 inhibits the mitochondrial pyruvate influx and simultaneously blocks glucose and lactate from fueling the mitochondrial respiration, thereupon relieving the hypoxia condition of tumors. Under a 5-min laser irradiation, the 7ACC2 carrying MOF@MOF nanoplatforms induced doubled cellular apoptosis and reduced 70% of the tumor growth compared with the cargo-free MOF@MOF. In summary, the design of this stable and hypoxia self-relievable MOF@MOF nanoplatform will enlighten the future development of MOF-based nanomedicines and PDT. STATEMENT OF SIGNIFICANCE: Though widely used for photodynamic therapy (PDT) in previous studies, porphyrinic metal-organic frameworks (MOFs) still face challenges in poor stability under physiological conditions and limited photodynamic efficiency due to the hypoxia condition of tumors. In order to solve these problems, (1) we develop the MOF@MOF strategy to improve the physiological stability; (2) an inhibitor of mitochondria pyruvate carrier, 7-amino carboxycoumarins-2 (7ACC2), is loaded to inhibit the mitochondrial pyruvate influx and simultaneously block glucose and lactate from fueling the mitochondrial respiration, thereupon relieving the hypoxia condition of tumors. In comparison with previous studies, our strategy simultaneously improves stability and overcomes the limited PDT efficiency in the hypoxia tumor tissue, which will enlighten the future development of MOF-based nanomedicines and PDT.
Asunto(s)
Estructuras Metalorgánicas , Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Estructuras Metalorgánicas/farmacología , Estructuras Metalorgánicas/química , Transportadores de Ácidos Monocarboxílicos , Neoplasias/tratamiento farmacológico , Hipoxia , Respiración , Mitocondrias , Lactatos , Glucosa , Piruvatos , Línea Celular Tumoral , Nanopartículas/químicaRESUMEN
Chemodynamic therapy (CDT) relies on the transformation of intracellular hydrogen peroxide (H2O2) to hydroxyl radicals (·OH) with higher toxicity under the catalysis of Fenton/Fenton-like reagents, which amplifies the oxidative stress and induces significant cellular apoptosis. However, the CDT efficacy is generally limited by the overexpressed GSH and insufficient endogenous H2O2 in tumors. Co-delivery of Cu2+ and glucose oxidase (GOD) can lead to a Cu2+/Cu+ circulation to realize GSH depletion and amplify the Fenton-like reaction. pH-responsive metal-organic frameworks (MOFs) are the optical choice to deliver Fenton/Fenton-like ions to tumors. However, considering that the aqueous condition is requisite for GOD encapsulation, it is challenging to abundantly dope Cu2+ in ZIF-8 MOF nanoparticles in aqueous conditions due to the ease of precipitation and enlarged crystal size. In this work, a robust one-pot biomimetic mineralization method using excessive ligand precursors in aqueous conditions is developed to synthesize GOD@Cu-ZIF-8. Copper ions abundantly doped to the GOD@Cu-ZIF-8 can eliminate GSH to produce Cu+, which is further proceeded to the Fenton-like reaction in the presence of GOD-catalyzed H2O2. Through breaking the tumor microenvironment homeostasis and producing an enhanced CDT effect, the promising antitumor capability of GOD@Cu-ZIF-8 was evidenced by the experiments both in vitro and in vivo.
Asunto(s)
Nanopartículas , Neoplasias , Humanos , Glucosa Oxidasa , Peróxido de Hidrógeno , Homeostasis , Estrés Oxidativo , Línea Celular Tumoral , Microambiente Tumoral , GlutatiónRESUMEN
Chemodynamic therapy (CDT) based on the Fe2+-mediated Fenton reaction can amplify intracellular oxidative stress by producing toxic â¢OH. However, the high-dose need for Fe2+ delivery in tumors and its significant cytotoxicity to normal tissues set a challenge. Therefore, a controllable delivery to activate the Fenton reaction and enhance Fe2+ tumor accumulation has become an approach to solve this conflict. Herein, we report a rare-earth-nanocrystal (RENC)-based Fe2+ delivery system using light-control techniques and DNA nanotechnology to realize programmable Fe2+ delivery. Ferrocenes, the source of Fe2+, are modified on the surface of RENCs through pH-responsive DNAs, which are further shielded by a PEG layer to elongate blood circulation and "turn off" the cytotoxicity of ferrocene. The up-/down-conversion dual-mode emissions of RENCs endow the delivery system with both capabilities of diagnosis and delivery control. The down-conversion NIR-II fluorescence can locate tumors. Consequently, up-conversion UV light spatiotemporally activates the catalytic activity of Fe2+ by shedding off the protective PEG layer. The exposed ferrocene-DNAs not only can "turn on" Fenton catalytic activity but also respond to tumor acidity, driving cross-linking and enhanced Fe2+ enrichment in tumors by 4.5-fold. Accordingly, this novel design concept will be inspiring for developing CDT nanomedicines in the future.
Asunto(s)
Metales de Tierras Raras , Nanopartículas , Neoplasias , Humanos , Luminiscencia , Fluorescencia , Metalocenos , Línea Celular Tumoral , Neoplasias/tratamiento farmacológico , Peróxido de Hidrógeno , Microambiente TumoralRESUMEN
BACKGROUND: To investigate the effect of ficin, a type of proteases, on Candida albicans (C. albicans) biofilm, including forming and pre-formed biofilms. METHODS: Crystal violet tests together with colony forming unit (CFU) counts were used to detect fungal biofilm biomass. Live/dead staining of biofilms observed by confocal laser scanning microscopy was used to monitor fungal activity. Finally, gene expression of C. albicans within biofilms was assessed by qRT-PCR. RESULTS: According to our results, biofilm biomass was dramatically reduced by ficin in both biofilm formation and pre-formed biofilms, as revealed by the crystal violet assay and CFU count (p < 0.05). Fungal activity in biofilm formation and pre-formed biofilms was not significantly influenced by ficin according to live/dead staining. Fungal polymorphism and biofilm associated gene expression were influenced by ficin, especially in groups with prominent antibiofilm effects. CONCLUSIONS: In summary, ficin effectively inhibited C. albicans biofilm formation and detached its preformed biofilm, and it might be used to treat C. albicans biofilm associated problems.
Asunto(s)
Candida albicans , Ficaína , Biopelículas , Ficaína/farmacología , Violeta de Genciana/farmacología , Humanos , Microscopía ConfocalRESUMEN
Alternative splicing enables a gene translating into different isoforms and into the corresponding proteoforms, which actually accomplish various biological functions of a living body. Isoform-isoform interactions (IIIs) provide a higher resolution interactome to explore the cellular processes and disease mechanisms than the canonically studied protein-protein interactions (PPIs), which are often recorded at the coarse gene level. The knowledge of IIIs is critical to map pathways, understand protein complexity and functional diversity, but the known IIIs are very scanty. In this paper, we propose a deep learning based method called DeepIII to systematically predict genome-wide IIIs by integrating diverse data sources, including RNA-seq datasets of different human tissues, exon array data, domain-domain interactions (DDIs) of proteins, nucleotide sequences and amino acid sequences. Particularly, DeepIII fuses these data to learn the representation of isoform pairs with a four-layer deep neural networks, and then performs binary classification on the learnt representation to achieve the prediction of IIIs. Experimental results show that DeepIII achieves a superior prediction performance to the state-of-the-art solutions and the III network constructed by DeepIII gives more accurate isoform function prediction. Case studies further confirm that DeepIII can differentiate the individual interaction partners of different isoforms spliced from the same gene. The code and datasets of DeepIII are available at http://mlda.swu.edu.cn/codes.php?name=DeepIII.
Asunto(s)
Empalme Alternativo , Redes Neurales de la Computación , Empalme Alternativo/genética , Humanos , Isoformas de Proteínas/genéticaRESUMEN
Minimal invasive phototherapy utilising near-infrared (NIR) laser to generate local reactive oxygen species (ROS) and heat has few associated side effects and is a precise treatment in cancer therapy. However, high-efficiency and safe phototherapeutic tumour agents still need developing. The application of iron hydroxide/oxide immobilised on reduced graphene oxide (FeOxH-rGO) nanocomposites as a therapeutic agent in integration photodynamic cancer therapy (PDT) and photothermal cancer therapy (PTT) was discussed. Under 808 nm NIR irradiation, FeOxH-rGO offers a high ROS generation and light-to-heat conversion efficiency because of its strong NIR absorption. These phototherapeutic effects lead to irreversible damage in FeOxH-rGO-treated T47D cells. Using a tumour-bearing mouse model, NIR ablated the breast tumour effectively in the presence of FeOxH-rGO. The tumour treatment response was evaluated to be 100%. We integrated PDT and PTT into a single nanodevice to facilitate effective cancer therapy. Our FeOxH-rGO, which integrates the merits of FeOxH and rGO, displays an outstanding tumoricidal capacity, suggesting the utilization of this nanocomposites in future medical applications.
RESUMEN
Recent investigations reveal that lactate is not a waste product but a major energy source for cells, especially in the mitochondria, which can support cellular survival under glucose shortage. Accordingly, the new understanding of lactate prompts to target it together with glucose to pursue a more efficient cancer starvation therapy. Herein, zeolitic imidazolate framework-8 (ZIF-8) nanoplatforms are used to co-deliver α-cyano-4-hydroxycinnamate (CHC) and glucose oxidase (GOx) and fulfill the task of simultaneous depriving of lactate and glucose, resulting in a new nanomedicine CHC/GOx@ZIF-8. The synthesis conditions are carefully optimized in order to yield monodisperse and uniform nanomedicines, which will ensure reliable and steady therapeutic properties. Compared with the strategies aiming at a single carbon source, improved starvation therapy efficacy is observed. Besides, more than boosting the energy shortage, CHC/GOx@ZIF-8 can block the lactate-fueled respiration and relieve solid tumor hypoxia, which will enhance GOx catalysis activity, depleting extra glucose, and producing more cytotoxic H2 O2 . By the synergistically enhanced anti-tumor effect, both in vitro and in vivo cancer-killing efficacies of CHC/GOx@ZIF-8 show twice enhancements than the GOx mediated therapy. The results demonstrate that the dual-depriving of lactate and glucose is a more advanced strategy for strengthening cancer starvation therapy.
Asunto(s)
Ácidos Cumáricos/metabolismo , Glucosa Oxidasa/metabolismo , Glucosa/metabolismo , Imidazoles/metabolismo , Ácido Láctico/metabolismo , Estructuras Metalorgánicas/metabolismo , Neoplasias/metabolismo , Neoplasias/terapia , Animales , Supervivencia Celular , Ratones , Nanomedicina/métodos , Nanopartículas/metabolismoRESUMEN
Understanding the evolutionary history and adaptive process depends on the knowledge that we can acquire from both ancient and modern genomic data. With the availability of a deluge of whole-genome sequencing data from ancient and modern goat samples, a user-friendly database making efficient reuse of these important resources is needed. Here, we use the genomes of 208 modern domestic goats, 24 bezoars, 46 wild ibexes, and 82 ancient goats to present a comprehensive goat genome variation database (GGVD). GGVD hosts a total of â¼41.44 million SNPs, â¼5.14 million indels, 6,193 selected loci, and 112 introgression regions. Users can freely visualize the frequency of genomic variations in geographical maps, selective sweeps in interactive tables, Manhattan plots, or line charts, as well as the heatmap patterns of the SNP genotype. Ancient data can be shown in haplotypes to track the state of genetic variants of selection and introgression events in the early, middle, and late stages. For facilitating access to sequence features, the UCSC Genome Browser, BLAT, BLAST, LiftOver, and pcadapt are also integrated into GGVD. GGVD will be a convenient tool for population genetic studies and molecular marker designing in goat breeding programs, and it is publicly available at http://animal.nwsuaf.edu.cn/GoatVar.
Asunto(s)
Genómica , Cabras , Animales , Selección GenéticaRESUMEN
A kind of nanoparticle is developed for highly efficient chemodynamic therapy that only relies on the endogenous H2O2 of cancer cells. For this nanoparticle, high-molecular-weight DNA is used as the biocompatible carrier to load abundant Mn2+ ions. Therefore, the resultant Mn-DNA coordination nanoparticles can efficiently deliver and sensitively release Mn2+ in cancer cells, resulting in high toxicity through the Fenton-like reaction.
Asunto(s)
ADN/química , Manganeso/farmacología , Nanopartículas/química , Neoplasias/terapia , Células A549 , Relación Dosis-Respuesta a Droga , Humanos , Manganeso/administración & dosificación , Manganeso/químicaRESUMEN
Copy number variation (CNV) is the most prevalent type of genetic structural variation that has been recognized as an important source of phenotypic variation in humans, animals and plants. However, the mechanisms underlying the evolution of CNVs and their function in natural or artificial selection remain unknown. Here, we generated CNV region (CNVR) datasets which were diverged or shared among cattle, goat, and sheep, including 886 individuals from 171 diverse populations. Using 9 environmental factors for genome-wide association study (GWAS), we identified a series of candidate CNVRs, including genes relating to immunity, tick resistance, multi-drug resistance, and muscle development. The number of CNVRs shared between species is significantly higher than expected (P<0.00001), and these CNVRs may be more persist than the single nucleotide polymorphisms (SNPs) shared between species. We also identified genomic regions under long-term balancing selection and uncovered the potential diversity of the selected CNVRs close to the important functional genes. This study provides the evidence that balancing selection might be more common in mammals than previously considered, and might play an important role in the daily activities of these ruminant species.
Asunto(s)
Variaciones en el Número de Copia de ADN , Rumiantes/genética , Animales , Bovinos , Frecuencia de los Genes , Genética de Población , Genoma/genética , Genómica , Genotipo , Cabras , Ganado/clasificación , Ganado/genética , Polimorfismo de Nucleótido Simple , Rumiantes/clasificación , Selección Genética , OvinosRESUMEN
Discovering driver pathways is an essential task to understand the pathogenesis of cancer and to design precise treatments for cancer patients. Increasing evidences have been indicating that multiple pathways often function cooperatively in carcinogenesis. In this study, we propose an approach called CDPath to discover cooperative driver pathways. CDPath first uses Integer Linear Programming to explore driver core modules from mutation profiles by enforcing co-occurrence and functional interaction relations between modules, and by maximizing the mutual exclusivity and coverage within modules. Next, to enforce cooperation of pathways and help the follow-up exact cooperative driver pathways discovery, it performs Markov clustering on pathway-pathway interaction network to cluster pathways. After that, it identifies pathways in different modules but in the same clusters as cooperative driver pathways. We apply CDPath on two TCGA datasets: breast cancer (BRCA) and endometrial cancer (UCEC). The results show that CDPath can identify known (i.e., TP53) and potential driver genes (i.e., SPTBN2). In addition, the identified cooperative driver pathways are related with the target cancer, and they are involved with carcinogenesis and several key biological processes. CDPath can uncover more potential biological associations between pathways (over 100 percent) and more cooperative driver pathways (over 200 percent) than competitive approaches. The demo codes of CDPath are available at http://mlda.swu.edu.cn/codes.php?name=CDPath.
Asunto(s)
Carcinogénesis/genética , Análisis por Conglomerados , Biología Computacional/métodos , Modelos Estadísticos , Algoritmos , Neoplasias de la Mama , Neoplasias Endometriales , Femenino , Redes Reguladoras de Genes , Humanos , Cadenas de Markov , Programas InformáticosRESUMEN
A widely used approach in transcriptome analysis is the alignment of short reads to a reference genome. However, owing to the deficiencies of specially designed analytical systems, short reads unmapped to the genome sequence are usually ignored, resulting in the loss of significant biological information and insights. To fill this gap, we present Comprehensive Assembly and Functional annotation of Unmapped RNA-Seq data (CAFU), a Galaxy-based framework that can facilitate the large-scale analysis of unmapped RNA sequencing (RNA-Seq) reads from single- and mixed-species samples. By taking advantage of machine learning techniques, CAFU addresses the issue of accurately identifying the species origin of transcripts assembled using unmapped reads from mixed-species samples. CAFU also represents an innovation in that it provides a comprehensive collection of functions required for transcript confidence evaluation, coding potential calculation, sequence and expression characterization and function annotation. These functions and their dependencies have been integrated into a Galaxy framework that provides access to CAFU via a user-friendly interface, dramatically simplifying complex exploration tasks involving unmapped RNA-Seq reads. CAFU has been validated with RNA-Seq data sets from wheat and Zea mays (maize) samples. CAFU is freely available via GitHub: https://github.com/cma2015/CAFU.
Asunto(s)
Biología Computacional/métodos , Análisis de Secuencia de ARN/métodos , Genes de Plantas , Humanos , ARN Mensajero/genética , Triticum/genética , Interfaz Usuario-Computador , Zea mays/genéticaRESUMEN
We utilize polymer micelle to precisely control indocyanine green (ICG) J-aggregation in a fast and highly efficient way. In addition to simple encapsulation, the polymer micelle plays a role as a host template to drive ICG J-aggregation by the synergy of electrostatic and hydrophobic attractions. We further demonstrate that, due to the robust host-guest interaction, the intact of ICG J-aggregate will be secured by the polymer encapsulation during the intracellular and in vivo incubation. These features make this hierarchical assembly between ICG J-aggregate and the micelle polymer a promising biomedicine for cancer phototheranostics. Therefore the complex micelles are further modified by introduction of doxorubicin for chemotherapy and DNA aptamer for tumor targeting, and the final multi-functional micellar medicine shows high therapeutic efficacy for tumor, i.e., the tumor can be completely eliminated with no local reoccurrence and without long-term toxicity or side effects during a 24-day period after the treatment.