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1.
Cell Chem Biol ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38776923

RESUMO

Circadian rhythms are intrinsic molecular mechanisms that synchronize biological functions with the day/night cycle. The mammalian gut is colonized by a myriad of microbes, collectively named the gut microbiota. The microbiota impacts host physiology via metabolites and structural components. A key mechanism is the modulation of host epigenetic pathways, especially histone modifications. An increasing number of studies indicate the role of the microbiota in regulating host circadian rhythms. However, the mechanisms remain largely unknown. Here, we summarize studies on microbial regulation of host circadian rhythms and epigenetic pathways, highlight recent findings on how the microbiota employs host epigenetic machinery to regulate circadian rhythms, and discuss its impacts on host physiology, particularly immune and metabolic functions. We further describe current challenges and resources that could facilitate research on microbiota-epigenetic-circadian rhythm interactions to advance our knowledge of circadian disorders and possible therapeutic avenues.

2.
Nat Commun ; 15(1): 133, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38168040

RESUMO

Adipocytes are the primary sites for fatty acid storage, but the synthesis rate of fatty acids is very low. The physiological significance of this phenomenon remains unclear. Here, we show that surplus fatty acid synthesis in adipocytes induces necroptosis and lipodystrophy. Transcriptional activation of FASN elevates fatty acid synthesis, but decreases NADPH level and increases ROS production, which ultimately leads to adipocyte necroptosis. We identify MED20, a subunit of the Mediator complex, as a negative regulator of FASN transcription. Adipocyte-specific male Med20 knockout mice progressively develop lipodystrophy, which is reversed by scavenging ROS. Further, in a murine model of HIV-associated lipodystrophy and a human patient with acquired lipodystrophy, ROS neutralization significantly improves metabolic disorders, indicating a causal role of ROS in disease onset. Our study well explains the low fatty acid synthesis rate in adipocytes, and sheds light on the management of acquired lipodystrophy.


Assuntos
Adipócitos , Lipodistrofia , Masculino , Camundongos , Humanos , Animais , Espécies Reativas de Oxigênio/metabolismo , Adipócitos/metabolismo , Lipodistrofia/genética , Lipodistrofia/metabolismo , Ácidos Graxos/metabolismo , Estresse Oxidativo , Camundongos Knockout
3.
J Acoust Soc Am ; 154(5): 3210-3222, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37971212

RESUMO

A parametric array loudspeaker (PAL) generates highly directional audible sound in air with a small aperture size compared to a conventional loudspeaker. But in indoor applications, the long propagation distance of a PAL causes reflections, which disturbs the reproduction of narrow audio beams. Moreover, sound distortion appears along the off-axis direction due to the frequency dependence of the beam width. This study proposed an optimal audio beam pattern synthesis for a PAL-based convex optimization, which can design the audio beam of a PAL with an optimal solution. The proposed method overcame the mentioned limitations by applying it to a length-limited PAL for audio spot control and a multichannel PAL array for a constant beam width audio beam. In a length-limited PAL, the proposed method restricts the audio spot to a smaller region and weakens the sound leakage along the off-axis direction. Whereas in a multichannel PAL array, the proposed method also achieves a constant beam width near the radiator axis. Simulations and experiments verify the effectiveness of the proposed method, which will enhance the performance of a PAL in scenarios where control of the audio beam is required.

5.
Science ; 381(6660): 851-857, 2023 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-37616368

RESUMO

The intestinal microbiota regulates mammalian lipid absorption, metabolism, and storage. We report that the microbiota reprograms intestinal lipid metabolism in mice by repressing the expression of long noncoding RNA (lncRNA) Snhg9 (small nucleolar RNA host gene 9) in small intestinal epithelial cells. Snhg9 suppressed the activity of peroxisome proliferator-activated receptor γ (PPARγ)-a central regulator of lipid metabolism-by dissociating the PPARγ inhibitor sirtuin 1 from cell cycle and apoptosis protein 2 (CCAR2). Forced expression of Snhg9 in the intestinal epithelium of conventional mice impaired lipid absorption, reduced body fat, and protected against diet-induced obesity. The microbiota repressed Snhg9 expression through an immune relay encompassing myeloid cells and group 3 innate lymphoid cells. Our findings thus identify an unanticipated role for a lncRNA in microbial control of host metabolism.


Assuntos
Microbioma Gastrointestinal , Intestinos , Metabolismo dos Lipídeos , PPAR gama , RNA Longo não Codificante , Sirtuína 1 , Animais , Camundongos , Imunidade Inata , Metabolismo dos Lipídeos/genética , Linfócitos/imunologia , PPAR gama/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Sirtuína 1/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Células Mieloides/imunologia , Intestinos/metabolismo , Intestinos/microbiologia , Tecido Adiposo/microbiologia , Humanos
6.
Genes Chromosomes Cancer ; 62(8): 460-470, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36862145

RESUMO

Gene fusions involving EWSR1 or FUS as the 5' partner have been reported in a diverse array of sarcomas. Here, we characterize the histopathology and genomics of six tumors harboring a gene fusion between EWSR1 or FUS and POU2AF3, an understudied, putative colorectal cancer predisposition gene. Striking morphologic features reminiscent of synovial sarcoma were observed including a biphasic appearance with variable fusiform to epithelioid cytomorphology and staghorn-type vasculature. RNA sequencing demonstrated variable breakpoints in EWSR1/FUS along with similar breakpoints in POU2AF3 that encompassed a 3' portion of this gene. For cases in which additional information was available, the behavior of these neoplasms was aggressive with local spread and/or distant metastases. Although further studies are needed to confirm the functional significance of our findings, POU2AF3 fusions to EWSR1 or FUS may define a novel type of POU2AF3-rearranged sarcomas with aggressive, malignant behavior.


Assuntos
Sarcoma Sinovial , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Proteína EWS de Ligação a RNA/genética , Sarcoma/genética , Neoplasias de Tecidos Moles/genética , Fusão Gênica , Hibridização in Situ Fluorescente , Biomarcadores Tumorais/genética , Proteínas de Fusão Oncogênica/genética , Proteínas de Neoplasias/genética , Proteína FUS de Ligação a RNA/genética
7.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 35(2): 195-200, 2023 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-36916381

RESUMO

OBJECTIVE: To investigate the preoperative nutritional status of cardiac surgery patients in southwest China, analyze the incidence and characteristics of nutritional risk, and provide basis for establishing a standardized individualized nutritional intervention program for cardiac surgery patients. METHODS: A cross-sectional survey was conducted on the nutritional status and intervention status of preoperative patients in cardiac surgery department of 23 general hospitals in Yunnan, Guizhou, Sichuan and Chongqing districts. At 00: 00 on July 7, 2022, the patients aged > 18 years old in cardiac surgery departments of the above hospitals who planned to undergo surgical treatment were enrolled as the survey objects to investigate the nutritional status on July 6, 2022 (the survey date), including basic information (general information, nutrition indicators, etc.), nutrition screening and evaluation (nutrition risk screening and organ support, etc.), nutrition treatment (nutrition supplement methods and prescriptions, etc.) and nutrition awareness of medical staff. RESULTS: The 126 questionnaires were collected, of which 125 were valid (99.2%). (1) Basic information: of the 125 patients, 67 patients were male (53.6%) and 58 patients were female (46.4%). The age ranged from 19 years old to 86 years old, with an average of (53.13±14.74) years old. Body mass index (BMI) was (22.21±3.78) kg/m2. The age and BMI of men were significantly higher than those of women [age (years old): 56.63±13.34 vs. 49.09±15.35, BMI (kg/m2): 22.74±3.86 vs. 21.59±3.61, both P < 0.05]. Of the 125 patients, 75 had valvular disease and 50 were with non-valvular diseases, which mainly included congenital heart disease [19 cases (15.2%)], aortic dissection [13 cases (10.4%)], coronary heart disease [12 cases (9.6%)], etc. The course of disease was 0.5 hour to 36 years, of which 93 patients (74.4%) were more than 6 months and 32 patients (25.6%) were equal to or less than 6 months. The proportion of female patients with disease duration > 6 months was significantly higher than that of male patients [87.9% (51/58) vs. 62.7% (42/67), P < 0.01]. The basic diseases mainly included hypertension [38 cases (30.4%)], coronary heart disease [12 cases (9.6%)], diabetes [7 cases (5.6%)], chronic obstructive pulmonary disease [COPD, 6 cases (4.8%)], etc. Among 125 patients, total protein (TP) < 60 g/L in 24 cases (19.2%), albumin (Alb) < 40 g/L in 64 cases (51.2%), anemia [male hemoglobin (Hb) < 120 g/L, female Hb < 110 g/L] in 33 cases (26.4%). A total of 60 cases of prealbumin data were collected, of which 23 cases (38.3%) were less than 200 mg/L. (2) Nutrition screening and assessment: 33.6% of the 125 patients did not undergo routine nutrition screening after admission, including the provincial and municipal tertiary hospitals. Among the 83 patients undergoing nutritional screening, 41 (32.8%) were at nutritional risk. Further analysis of patients with nutritional risk showed that of the 41 patients, 20 were male (48.8%) and 21 were female (51.2%); 27 cases (65.9%) was with valvular diseases and 14 cases (34.1%) was with non-valvular diseases; the course of disease was more than 6 months in 30 cases (73.2%), and ≤ 6 months in 11 cases (26.7%). Statistical comparison of the above 83 patients showed that women, basic disease, long term-valvular disease, anemia, low TP, and low Alb before operation were more prone to innutrition. (3) Nutritional therapy: of the 125 patients, 5 were receiving mechanical ventilation (4.0%) and 2 were using vasoactive drugs (1.6%); there were 5 cases with gastrointestinal dysfunction (4.0%), mainly manifested as abdominal distension, abdominal pain, constipation and diarrhea. One patient was treated with enteral nutrition through gastric tube combined with parenteral nutrition support, 124 patients were fed orally, and an irregular phenomenon of injecting amino acid fat emulsion through peripheral vein in 2 patients. (4) Nutrition awareness of medical staff: 124 (99.2%) of the 125 patients had a nutrition department in their hospital; 71 cases (56.8%) received nutrition education, of which 37 cases (52.1%) were consulted by the nutrition department. Of all the cases, only 38 (30.4%) were consulted by the nutrition department, of which 1 (2.6%) did not receive nutrition education after consultation. CONCLUSIONS: At present, the incidence of preoperative malnutrition in patients undergoing cardiac surgery is high in southwest China. The incidence of malnutrition in patients with basic diseases, long term-valvular disease, low TP, low Alb and anemia before operation is higher, and the incidence of malnutrition is hidden in women. The course of disease of women is longer than that of men at the time of treatment, and malnutrition is more likely to occur. The attending physicians should pay attention to the above groups. It is necessary to establish a standardized individualized nutritional intervention program and apply it to actual clinical diagnosis and treatment, so as to ultimately improve the prognosis of patients undergoing cardiac surgery and increase the benefits of patients in treatment.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Desnutrição , Doença Pulmonar Obstrutiva Crônica , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Adolescente , Estado Nutricional , Estudos Transversais , Avaliação Nutricional , China/epidemiologia , Desnutrição/epidemiologia , Desnutrição/diagnóstico
8.
JCO Precis Oncol ; 7: e2200300, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36623238

RESUMO

PURPOSE: Programmed cell death protein-1 (PD-1) receptor and ligand interactions are the target of immunotherapies for more than 20 cancer types. Biomarkers that predict response to immunotherapy are microsatellite instability, tumor mutational burden, and programmed death ligand-1 (PD-L1) immunohistochemistry. Structural variations (SVs) in PD-L1 (CD274) and PD-L2 (PDCD1LG2) have been observed in cancer, but the comprehensive landscape is unknown. Here, we describe the genomic landscape of PD-L1 and PD-L2 SVs, their potential impact on the tumor microenvironment, and evidence that patients with these alterations can benefit from immunotherapy. METHODS: We analyzed sequencing data from cancer cases with PD-L1 and PD-L2 SVs across 22 publications and four data sets, including Foundation Medicine Inc, The Cancer Genome Atlas, International Cancer Genome Consortium, and the Oncology Research Information Exchange Network. We leveraged RNA sequencing to evaluate immune signatures. We curated literature reporting clinical outcomes of patients harboring PD-L1 or PD-L2 SVs. RESULTS: Using data sets encompassing 300,000 tumors, we curated 486 cases with SVs in PD-L1 and PD-L2 and observed consistent breakpoint patterns, or hotspots. Leveraging The Cancer Genome Atlas, we observed significant upregulation in PD-L1 expression and signatures for interferon signaling, macrophages, T cells, and immune cell proliferation in samples harboring PD-L1 or PD-L2 SVs. Retrospective review of 12 studies that identified patients with SVs in PD-L1 or PD-L2 revealed > 50% (52/71) response rate to PD-1 immunotherapy with durable responses. CONCLUSION: Our findings show that the 3'-UTR is frequently affected, and that SVs are associated with increased expression of ligands and immune signatures. Retrospective evidence from curated studies suggests this genomic alteration could help identify candidates for PD-1/PD-L1 immunotherapy. We expect these findings will better define PD-L1 and PD-L2 SVs in cancer and lend support for prospective clinical trials to target these alterations.


Assuntos
Antígeno B7-H1 , Neoplasias , Humanos , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Receptor de Morte Celular Programada 1/genética , Ligantes , Estudos Retrospectivos , Estudos Prospectivos , Neoplasias/genética , Neoplasias/terapia , Microambiente Tumoral/genética
9.
NPJ Precis Oncol ; 7(1): 10, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36690680

RESUMO

In this study, we report the clinicopathologic and genomic profiles of 891 patients with RET fusion driven advanced solid tumors. All patient samples were tested using a tissue-based DNA hybrid capture next generation sequencing (NGS) assay and a subset of the samples were liquid biopsies tested using a liquid-based hybrid capture NGS assay. RET fusions were found in 523 patients with NSCLC and in 368 patients with other solid tumors. The two tumor types with the highest number of RET fusion were lung adenocarcinoma and thyroid papillary carcinoma, and they had a prevalence rate 1.14% (455/39,922) and 9.09% (109/1199), respectively. A total of 61 novel fusions were discovered in this pan-tumor cohort. The concordance of RET fusion detection across tumor types among tissue and liquid-based NGS was 100% (8/8) in patients with greater than 1% composite tumor fraction (cTF). Herein, we present the clinicopathologic and genomic landscape of a large cohort of RET fusion positive tumors and we observed that liquid biopsy-based NGS is highly sensitive for RET fusions at cTF ≥1%.

10.
Methods Mol Biol ; 2595: 239-250, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36441467

RESUMO

MicroRNAs (miRNAs) are endogenous non-coding small RNAs, which regulate gene expression at the post-transcriptional level. A large number of studies have revealed that they play key roles in diverse life activities, such as growth and development. In the last decade, deep sequencing technology has generated substantial small RNA sequencing (sRNA-Seq) data. Meanwhile, numerous tools have been developed to identify miRNAs from these sRNA-Seq data, resulting in a surge of miRNA annotations. Among these tools, the series of miRDeep-P and miRDeep-P2 have been widely used in plant miRNA annotation. Here, we employed miRDeep-P2 to demonstrate the plant miRNA annotation processes step by step using the deep sequencing data.


Assuntos
MicroRNAs , MicroRNAs/genética , Análise de Sequência de RNA , Tecnologia , Sequenciamento do Exoma , Sequenciamento de Nucleotídeos em Larga Escala
11.
Plant Commun ; 4(1): 100425, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-35964156

RESUMO

As a globally popular leafy vegetable and a representative plant of the Asteraceae family, lettuce has great economic and academic significance. In the last decade, high-throughput sequencing, phenotyping, and other multi-omics data in lettuce have accumulated on a large scale, thus increasing the demand for an integrative lettuce database. Here, we report the establishment of a comprehensive lettuce database, LettuceGDB (https://www.lettucegdb.com/). As an omics data hub, the current LettuceGDB includes two reference genomes with detailed annotations; re-sequencing data from over 1000 lettuce varieties; a collection of more than 1300 worldwide germplasms and millions of accompanying phenotypic records obtained with manual and cutting-edge phenomics technologies; re-analyses of 256 RNA sequencing datasets; a complete miRNAome; extensive metabolite information for representative varieties and wild relatives; epigenetic data on the genome-wide chromatin accessibility landscape; and various lettuce research papers published in the last decade. Five hierarchically accessible functions (Genome, Genotype, Germplasm, Phenotype, and O-Omics) have been developed with a user-friendly interface to enable convenient data access. Eight built-in tools (Assembly Converter, Search Gene, BLAST, JBrowse, Primer Design, Gene Annotation, Tissue Expression, Literature, and Data) are available for data downloading and browsing, functional gene exploration, and experimental practice. A community forum is also available for information sharing, and a summary of current research progress on different aspects of lettuce is included. We believe that LettuceGDB can be a comprehensive functional database amenable to data mining and database-driven exploration, useful for both scientific research and lettuce breeding.


Assuntos
Genômica , Lactuca , Lactuca/genética , Genótipo , Fenótipo , Plantas
12.
Int J Mol Sci ; 23(22)2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36430750

RESUMO

MicroRNAs (miRNAs) are an important class of regulatory small RNAs that program gene expression, mainly at the post-transcriptional level. Although sporadic examples of species-specific miRNAs (termed SS-miRNAs) have been reported, a genome-scale study across a variety of distant species has not been assessed. Here, by comprehensively analyzing miRNAs in 81 plant species phylogenetically ranging from chlorophytes to angiosperms, we identified 8048 species-specific miRNAs from 5499 families, representing over 61.2% of the miRNA families in the examined species. An analysis of the conservation from different taxonomic levels supported the high turnover rate of SS-miRNAs, even over short evolutionary distances. A comparison of the intrinsic features between SS-miRNAs and NSS-miRNAs (non-species-specific miRNAs) indicated that the AU content of mature miRNAs was the most striking difference. Our data further illustrated a significant bias of the genomic coordinates towards SS-miRNAs lying close to or within genes. By analyzing the 125,267 putative target genes for the 7966 miRNAs, we found the preferentially regulated functions of SS-miRNAs related to diverse metabolic processes. Collectively, these findings underscore the dynamic evolution of miRNAs in the species-specific lineages.


Assuntos
Magnoliopsida , MicroRNAs , Humanos , MicroRNAs/genética , Especificidade da Espécie , Genômica
13.
Mol Biol Evol ; 39(11)2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36223453

RESUMO

MicroRNAs (miRNAs) are fast evolving endogenous small RNAs that regulate organism function and behavior in both animals and plants. Although models for de novo miRNA biogenesis have been proposed, the genomic mechanisms driving swift diversification of the miRNA repertoires in plants remain elusive. Here, by comprehensively analyzing 21 phylogenetically representative plant species, ranging from green algae to angiosperms, we systematically identified de novo miRNA events associated with 8,649 miRNA loci. We found that 399 (4.6%), 466 (5.4%), and 1,402 (16.2%) miRNAs were derived from inverted gene duplication events, long terminal repeats of retrotransposons, and miniature inverted-repeat transposable elements (MITEs), respectively. Among the miRNAs of these origins, MITEs, especially those belonging to the Mutator, Tc1/Mariner, and PIF/Harbinger superfamilies, were the predominant genomic source for de novo miRNAs in the 15 examined angiosperms but not in the six non-angiosperms. Our data further illustrated a transposition-transcription process by which MITEs are converted into new miRNAs (termed MITE-miRNAs) whereby properly sized MITEs are transcribed and therefore become potential substrates for the miRNA processing machinery by transposing into introns of active genes. By analyzing the 58,038 putative target genes for the 8,095 miRNAs, we found that the target genes of MITE-miRNAs were preferentially associated with response to environmental stimuli such as temperature, suggesting that MITE-miRNAs are pertinent to plant adaptation. Collectively, these findings demonstrate that molecular conversion of MITEs is a genomic mechanism leading to rapid and continuous changes to the miRNA repertoires in angiosperm.


Assuntos
Magnoliopsida , MicroRNAs , Animais , MicroRNAs/genética , Elementos de DNA Transponíveis/genética , Magnoliopsida/genética , Duplicação Gênica , Retroelementos , Plantas/genética , Sequências Repetidas Invertidas
14.
Front Plant Sci ; 13: 848474, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35599893

RESUMO

MicroRNA (miRNA) is an essential endogenous post-transcriptional regulatory factor, and foxtail millet (Setaria italica L.) is an ideal C4 model cereal that is a highly valuable crop in semiarid and arid areas. The Research on comprehensive and high confidence identification and annotation of foxtail millet miRNAs needs to be strengthened, and to our knowledge, there is no information on the regulatory network of foxtail millet miRNA. In this study, 136 high confidence miRNAs were identified through high-throughput sequencing of the small RNAs in seven tissues at the shooting and grain filling stages of foxtail millet. A total of 2,417 target genes were obtained by combining computational biology software and degradome sequencing methods. Furthermore, an analysis using transcriptome sequencing revealed the relationships between miRNAs and their target genes and simultaneously explored key regulatory modules in panicles during the grain filling stage. An miRNA regulatory network was constructed to explore the functions of miRNA in more detail. This network, centered on miRNAs and combining upstream transcriptional factors and downstream target genes, is primarily composed of feed forward loop motifs, which greatly enhances our knowledge of the potential functions of miRNAs and uncovers numerous previously unknown regulatory links. This study provides a solid foundation for research on the function and regulatory network of miRNAs in foxtail millet.

15.
Nucleic Acids Res ; 50(D1): D1475-D1482, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34554254

RESUMO

Nearly 200 plant genomes have been sequenced over the last two years, and new functions of plant microRNAs (miRNAs) have been revealed. Therefore, timely update of the plant miRNA databases by incorporating miRNAs from the newly sequenced species and functional information is required to provide useful resources for advancing plant miRNA research. Here we report the update of PmiREN2.0 (https://pmiren.com/) with an addition of 19 363 miRNA entries from 91 plants, doubling the amount of data in the original version. Meanwhile, abundant regulatory information centred on miRNAs was added, including predicted upstream transcription factors through binding motifs scanning and elaborate annotation of miRNA targets. As an example, a genome-wide regulatory network centred on miRNAs was constructed for Arabidopsis. Furthermore, phylogenetic trees of conserved miRNA families were built to expand the understanding of miRNA evolution across the plant lineages. These data are helpful to deduce the regulatory relationships concerning miRNA functions in diverse plants. Beside the new data, a suite of design tools was incorporated to facilitate experimental practice. Finally, a forum named 'PmiREN Community' was added for discussion and resource and new discovery sharing. With these upgrades, PmiREN2.0 should serve the community better and accelerate miRNA research in plants.


Assuntos
Bases de Dados Genéticas , MicroRNAs/genética , Plantas/genética , Software , Biologia Computacional/normas , Regulação da Expressão Gênica de Plantas/genética , Genoma de Planta/genética , MicroRNAs/classificação
16.
Science ; 374(6568): eabe6723, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34735226

RESUMO

A diverse group of antimicrobial proteins (AMPs) helps protect the mammalian intestine from varied microbial challenges. We show that small proline-rich protein 2A (SPRR2A) is an intestinal antibacterial protein that is phylogenetically unrelated to previously discovered mammalian AMPs. In this study, SPRR2A was expressed in Paneth cells and goblet cells and selectively killed Gram-positive bacteria by disrupting their membranes. SPRR2A shaped intestinal microbiota composition, restricted bacterial association with the intestinal surface, and protected against Listeria monocytogenes infection. SPRR2A differed from other intestinal AMPs in that it was induced by type 2 cytokines produced during helminth infection. Moreover, SPRR2A protected against helminth-induced bacterial invasion of intestinal tissue. Thus, SPRR2A is a distinctive AMP triggered by type 2 immunity that protects the intestinal barrier during helminth infection.


Assuntos
Proteínas Ricas em Prolina do Estrato Córneo/metabolismo , Microbioma Gastrointestinal , Bactérias Gram-Positivas/fisiologia , Mucosa Intestinal/metabolismo , Intestinos/microbiologia , Nematospiroides dubius , Infecções por Strongylida/imunologia , Animais , Carga Bacteriana , Membrana Celular/metabolismo , Permeabilidade da Membrana Celular , Proteínas Ricas em Prolina do Estrato Córneo/genética , Citocinas/metabolismo , Suscetibilidade a Doenças , Células Caliciformes/metabolismo , Humanos , Imunidade Inata , Mucosa Intestinal/microbiologia , Listeria monocytogenes/fisiologia , Listeriose/microbiologia , Camundongos , Viabilidade Microbiana , Celulas de Paneth/metabolismo , Proteínas Citotóxicas Formadoras de Poros/genética , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Infecções por Strongylida/metabolismo , Infecções por Strongylida/microbiologia
17.
J Immunother Cancer ; 9(11)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34815356

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) benefit patients with multiple cancer types, however, additional predictive biomarkers of response are needed. CD274 (programmed cell death ligand-1, PD-L1) gene rearrangements are positively associated with PD-L1 expression and may confer benefit to ICI, thus a pan-cancer characterization of these alterations is needed. METHODS: We analyzed 283,050 patient samples across multiple tumor types that underwent comprehensive genomic profiling for activating CD274 rearrangements and other alterations. The DAKO 22C3 Tumor Proportion Scoring (TPS) method was used for PD-L1 immunohistochemistry (IHC) testing in a small subset with available data (n=55,423). A retrospective deidentified real-world clinico-genomic database (CGDB) was examined for ICI treatment outcomes. We also report a detailed case of CD274-rearranged metastatic rectal adenocarcinoma. RESULTS: We identified 145 samples with functional rearrangements in CD274. There were significant enrichments for PIK3CA, JAK2, PDCD1LG2, CREBBP, and PBRM1 co-mutations (ORs=2.1, 16.7, 17.8, 3.6, and 3.4, respectively, p<0.01). Genomic human papillomavirus (HPV)-16, Epstein-Barr virus, and mismatch repair genes also co-occurred (OR=6.2, 8.4, and 4.3, respectively, p<0.05). Median tumor mutational burden (TMB) was higher compared with CD274 wild-type samples (7.0 vs 3.5 mutations/Mb, p=1.7e-11), with disease-specific TMB enrichment in non-small cell lung, colorectal, unknown primary, and stomach cancers. PD-L1 IHC skewed toward positivity (N=39/43 samples with ≥1% positivity). Of eight patients from the CGDB, three remained on ICI treatment after 6 months. Separately, one patient with metastatic rectal adenocarcinoma experienced a pathologic complete response on chemoimmunotherapy. CONCLUSIONS: CD274 gene rearrangements are associated with increased PD-L1 IHC scores, higher TMB, and potential clinical benefit in ICI-treated patients with cancer.


Assuntos
Antígeno B7-H1/metabolismo , Imunoterapia/métodos , Neoplasias/tratamento farmacológico , Adulto , Feminino , Humanos
18.
Brief Bioinform ; 22(5)2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-33754625

RESUMO

Last two decades, the studies on microRNAs (miRNAs) and the numbers of annotated miRNAs in plants and animals have surged. Herein, we reviewed the current progress and challenges of miRNA annotation in plants. Via the comparison of plant and animal miRNAs, we pinpointed out the difficulties on plant miRNA annotation and proposed potential solutions. In terms of recalling the history of methods and criteria in plant miRNA annotation, we detailed how the major progresses made and evolved. By collecting and categorizing bioinformatics tools for plant miRNA annotation, we surveyed their advantages and disadvantages, especially for ones with the principle of mimicking the miRNA biogenesis pathway by parsing deeply sequenced small RNA (sRNA) libraries. In addition, we summarized all available databases hosting plant miRNAs, and posted the potential optimization solutions such as how to increase the signal-to-noise ratio (SNR) in these databases. Finally, we discussed the challenges and perspectives of plant miRNA annotations, and indicated the possibilities offered by an all-in-one tool and platform according to the integration of artificial intelligence.


Assuntos
Biologia Computacional/métodos , Bases de Dados Genéticas , MicroRNAs/genética , Plantas/genética , RNA de Plantas/genética , Inteligência Artificial , Biologia Computacional/estatística & dados numéricos , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes/genética , Anotação de Sequência Molecular/métodos , Plantas/classificação
20.
IEEE Trans Vis Comput Graph ; 27(1): 83-97, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31449026

RESUMO

We present a learning-based approach to reconstructing high-resolution three-dimensional (3D) shapes with detailed geometry and high-fidelity textures. Albeit extensively studied, algorithms for 3D reconstruction from multi-view depth-and-color (RGB-D) scans are still prone to measurement noise and occlusions; limited scanning or capturing angles also often lead to incomplete reconstructions. Propelled by recent advances in 3D deep learning techniques, in this paper, we introduce a novel computation- and memory-efficient cascaded 3D convolutional network architecture, which learns to reconstruct implicit surface representations as well as the corresponding color information from noisy and imperfect RGB-D maps. The proposed 3D neural network performs reconstruction in a progressive and coarse-to-fine manner, achieving unprecedented output resolution and fidelity. Meanwhile, an algorithm for end-to-end training of the proposed cascaded structure is developed. We further introduce Human10, a newly created dataset containing both detailed and textured full-body reconstructions as well as corresponding raw RGB-D scans of 10 subjects. Qualitative and quantitative experimental results on both synthetic and real-world datasets demonstrate that the presented approach outperforms existing state-of-the-art work regarding visual quality and accuracy of reconstructed models.

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