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1.
Nat Methods ; 20(1): 35, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36635549
2.
Nucleic Acids Res ; 51(D1): D1-D8, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36624667

RESUMO

The 2023 Nucleic Acids Research Database Issue contains 178 papers ranging across biology and related fields. There are 90 papers reporting on new databases and 82 updates from resources previously published in the Issue. Six more papers are updates from databases most recently published elsewhere. Major nucleic acid databases reporting updates include Genbank, ENA, ChIPBase, JASPAR, mirDIP and the Issue's first Breakthrough Article, NACDDB for Circular Dichroism data. Updates from BMRB and RCSB cover experimental protein structural data while AlphaFold 2 computational structure predictions feature widely. STRING and REBASE are stand-out updates in the signalling and enzymes section. Immunology-related databases include CEDAR, the second Breakthrough Article, for cancer epitopes and receptors alongside returning IPD-IMGT/HLA and the new PGG.MHC. Genomics-related resources include Ensembl, GWAS Central and UCSC Genome Browser. Major returning databases for drugs and their targets include Open Targets, DrugCentral, CTD and Pubchem. The EMPIAR image archive appears in the Issue for the first time. The entire database Issue is freely available online on the Nucleic Acids Research website (https://academic.oup.com/nar). The NAR online Molecular Biology Database Collection has been updated, revisiting 463 entries, adding 92 new resources and eliminating 96 discontinued URLs so bringing the current total to 1764 databases. It is available at http://www.oxfordjournals.org/nar/database/c/.


Assuntos
Bases de Dados de Ácidos Nucleicos , Biologia Molecular , Ácidos Nucleicos , Biologia Computacional , Internet , Publicações Periódicas como Assunto
3.
Methods Enzymol ; 678: 1-22, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36641205

RESUMO

Key to small-angle scattering (SAS) maturing and becoming a mainstream structural biology technique was the work done by the SAS community to establish standards for data quality, model validation and data sharing. Through a consultative process spanning more than a decade and a half, guidelines for publication have been established that include criteria for evaluating data quality and for model validation. In this process gaps were identified that stimulated innovation and development of new tools, for example new measures of model ambiguity and of the goodness-of-fit of a model to SAS data that complement the traditional global fit parameter χ2. The need for a global repository for biomolecular SAS data and models was identified and the SASBDB was established as a searchable, curated, freely accessible, downloadable database of experimental data, experimental conditions, sample details, derived models, and their fit to the data. Importantly, the SASBDB uses a common dictionary format that supports archiving of structures solved using integrative methods to support seamless data exchange with a federated system of public databanks that includes the world-wide Protein Data Bank (wwPDB) as the major repository for structural biology. Thus, biomolecular SAS is now well-positioned to achieve its full potential as a mainstream structural biology technique contributing at the frontier of integrative structural biology and meeting "best practice" standards for data quality assurance and data sharing.


Assuntos
Confiabilidade dos Dados , Biologia Molecular , Modelos Moleculares , Bases de Dados de Proteínas , Espalhamento a Baixo Ângulo , Disseminação de Informação
5.
Int J Mol Sci ; 24(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36674640

RESUMO

There is a clear association between the molecular profile of colorectal cancer liver metastases (CRCLM) and the degree to which aggressive progression of the disease impacts patient survival. However, much of our knowledge of the molecular behaviour of colorectal cancer cells comes from experimental studies with, as yet, limited application in clinical practice. In this article, we review the current advances in the understanding of the molecular behaviour of CRCLM and present possible future therapeutic applications. This review focuses on three important steps in CRCLM development, progression and treatment: (1) the dissemination of malignant cells from primary tumours and the seeding to metastatic sites; (2) the response to modern regimens of chemotherapy; and (3) the possibility of predicting early progression and recurrence patterns by molecular analysis in liquid biopsy.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Seguimentos , Neoplasias Colorretais/terapia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamento farmacológico , Biologia Molecular
6.
Int J Mol Sci ; 24(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36674932

RESUMO

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death globally. The cancer stem cells (CSCs) of HCC are responsible for tumor growth, invasion, metastasis, recurrence, chemoresistance, target therapy resistance and radioresistance. The reported main surface markers used to identify liver CSCs include epithelial cell adhesion/activating molecule (EpCAM), cluster differentiation 90 (CD90), CD44 and CD133. The main molecular signaling pathways include the Wnt/ß-catenin, transforming growth factors-ß (TGF-ß), sonic hedgehog (SHH), PI3K/Akt/mTOR and Notch. Patients with EpCAM-positive alpha-fetoprotein (AFP)-positive HCC are usually young but have advanced tumor-node-metastasis (TNM) stages. CD90-positive HCCs are usually poorly differentiated with worse prognosis. Those with CD44-positive HCC cells develop early metastases. Those with CD133 expression have a higher recurrence rate and a shorter overall survival. The Wnt/ß-catenin signaling pathway triggers angiogenesis, tumor infiltration and metastasis through the enhancement of angiogenic factors. All CD133+ liver CSCs, CD133+/EpCAM+ liver CSCs and CD44+ liver CSCs contribute to sorafenib resistance. SHH signaling could protect HCC cells against ionizing radiation in an autocrine manner. Reducing the CSC population of HCC is crucial for the improvement of the therapy of advanced HCC. However, targeting CSCs of HCC is still challenging.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Molécula de Adesão da Célula Epitelial/genética , Molécula de Adesão da Célula Epitelial/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Hedgehog/metabolismo , Via de Sinalização Wnt , Linhagem Celular Tumoral , Células-Tronco Neoplásicas/metabolismo , Biologia Molecular
7.
Biomolecules ; 13(1)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36671499

RESUMO

Archaea represents the third domain of life, displaying a closer relationship with eukaryotes than bacteria. These microorganisms are valuable model systems for molecular biology and biotechnology. In fact, nowadays, methanogens, halophiles, thermophilic euryarchaeota, and crenarchaeota are the four groups of archaea for which genetic systems have been well established, making them suitable as model systems and allowing for the increasing study of archaeal genes' functions. Furthermore, thermophiles are used to explore several aspects of archaeal biology, such as stress responses, DNA replication and repair, transcription, translation and its regulation mechanisms, CRISPR systems, and carbon and energy metabolism. Extremophilic archaea also represent a valuable source of new biomolecules for biological and biotechnological applications, and there is growing interest in the development of engineered strains. In this review, we report on some of the most important aspects of the use of archaea as a model system for genetic evolution, the development of genetic tools, and their application for the elucidation of the basal molecular mechanisms in this domain of life. Furthermore, an overview on the discovery of new enzymes of biotechnological interest from archaea thriving in extreme environments is reported.


Assuntos
Archaea , Euryarchaeota , Archaea/metabolismo , Bactérias/genética , Euryarchaeota/genética , Euryarchaeota/metabolismo , Biotecnologia , Biologia Molecular
8.
Leuk Res ; 124: 107002, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36563650

RESUMO

BACKGROUND: Philadelphia chromosome-positive acute myeloid leukemia (Ph+ AML) is a provisional disease entity in the 2016 WHO classification, while its genetic profile of Ph+ AML remains poorly defined. In addition, the differentiating features of Ph+ AML and chronic myeloid leukemia in myeloid blast crisis (CML-MBC) remain controversial. METHODS: We conducted a retrospective study of 15 Ph+ AML patients to compare their clinical and laboratory profiles with 27 CML-MBC patients. RESULTS: Compared to CML-MBC, Ph+ AML patients presented with significantly higher peripheral WBC count and bone marrow blast percentage. The immunophenotypic profiles were largely similar between Ph+ AML and CML-MBC, except for CD4 expression, which was significantly enriched in CML-MBC. Ph+ AML patients less frequently harboured co-occurring additional cytogenetic abnormalities (ACA) compared to CML-MBC, and trisomy 19 (23%) and IDH1/2 (46%) were the most common ACA and mutated genes in Ph+ AML, respectively. Overall survival (OS) did not significantly differ between Ph+ AML and CML-MBC. Ph+ AML without CML-like features appeared to have a better outcome compared to Ph+ AML with CML-like features; ACA in Ph+ AML may confer an even worse prognosis. CONCLUSIONS: Our results indicate that patients with Ph+ AML share similar genetic profiles and clinical outcomes with those with CML-MBC, thus should be classified as a high-risk entity.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Mieloide Aguda , Humanos , Cromossomo Filadélfia , Estudos Retrospectivos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mieloide Aguda/genética , Biologia Molecular
9.
Methods Mol Biol ; 2588: 91-104, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36418684

RESUMO

In their natural environments, microorganisms usually live in organized communities. Profiling analysis of microbial communities has recently assumed special relevance as it allows a thorough understanding of the diversity of the microbiota, its behavior over time, and the establishment of patterns associated with health and disease. The application of molecular biology approaches holds the advantage of including culture-difficult and as-yet-uncultivated phylotypes in the profiles, providing a more comprehensive picture of the microbial community. This chapter focuses on two particular techniques, namely terminal restriction fragment length polymorphism (T-RFLP) and denaturing gradient gel electrophoresis (DGGE), both of which have been widely used in environmental studies and have been recently successfully used by the authors in the study of the oral microbial communities associated with conditions of health and disease.


Assuntos
Microbiota , Polimorfismo de Fragmento de Restrição , Eletroforese em Gel de Gradiente Desnaturante , Microbiota/genética , Biologia Molecular
10.
J Agric Food Chem ; 71(1): 20-34, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36573879

RESUMO

Mango (Mangifera indica L.) is a nutritionally important fruit of high nutritive value, delicious in taste with an attractive aroma. Due to their antioxidant and therapeutic potential, mango fruits are receiving special attention in biochemical and pharmacognosy-based studies. Fruit quality determines consumer's acceptance, and hence, understanding the physiological, biochemical, and molecular basis of fruit development, maturity, ripening, and storage is essential. Transcriptomic, metabolomic, proteomic, and molecular genetic approaches have led to the identification of key genes, metabolites, protein candidates, and quantitative trait loci that are associated with enhanced mango fruit quality. The major pathways that determine the fruit quality include amino acid metabolism, plant hormone signaling, carbohydrate metabolism and transport, cell wall biosynthesis and degradation, flavonoid and anthocyanin biosynthesis, and carotenoid metabolism. Expression of the polygalacturonase, cutin synthase, pectin methyl esterase, pectate lyase, ß-galactosidase, and ethylene biosynthesis enzymes are related to mango fruit ripening, flavor, firmness, softening, and other quality processes, while genes involved in the MAPK signaling pathway, heat shock proteins, hormone signaling, and phenylpropanoid biosynthesis are associated with diseases. Metabolomics identified volatiles, organic acids, amino acids, and various other compounds that determine the characteristic flavor and aroma of the mango fruit. Molecular markers differentiate the mango cultivars based on their geographical origins. Genetic linkage maps and quantitative trait loci studies identified regions in the genome that are associated with economically important traits. The review summarizes the applications of omics techniques and their potential applications toward understanding mango fruit physiology and their usefulness in future mango breeding.


Assuntos
Mangifera , Transcriptoma , Mangifera/genética , Frutas/química , Proteômica , Melhoramento Vegetal , Biologia Molecular
13.
Methods Mol Biol ; 2560: 41-66, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36481882

RESUMO

Retinitis pigmentosa (RP) affects approximately 1 in 4000 individuals. It has many different genetic etiologies and therefore diagnosis can be challenging. Understanding the different testing methodologies is beneficial for clinicians and researchers in order to select the best testing method, whether it be panel testing, whole exome sequencing, or whole genome sequencing for individuals affected with RP. The Methods section also outlines the steps required to complete a WES assay, which has become a popular method for identifying the molecular diagnosis for individuals with RP.


Assuntos
Retinite Pigmentosa , Humanos , Retinite Pigmentosa/diagnóstico , Retinite Pigmentosa/genética , Biologia Molecular
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(6): 1845-1850, 2022 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-36476914

RESUMO

OBJECTIVE: To analyze the reasons for ABO blood group forward typing and reverse typing incompatibility of the proband by serological and molecular biological tests, so as to clarify the blood group and genetic rules and determine the reasonable transfusion strategy. METHODS: On the basis of serological testing results, PCR-SSP method was utilized for the ABO exon sequencing in the peripheral blood of the proband and 5 family members, and blood group results were comprehensively analyzed. RESULTS: The serological results of ABO blood group of the proband were incompatibility, and the molecular biological test results showed that there was a c.700C>G mutation compared with B101, which was consistent with B(A)02 subtype, and the genotype was B(A)02/O02. The results of the elder brother was the same as the proband. The nephew of the proband also detected c.700C>G, genotype A102/B(A) 02. CONCLUSION: When the result of standard serological test for ABO blood group incompatibility occurs, using molecular biology detection technology to explore mutation is an effective method to confirm ABO subtype, and ensures the safety of clinical blood transfusion.


Assuntos
Sistema ABO de Grupos Sanguíneos , Biologia Molecular , Humanos , Idoso , Sistema ABO de Grupos Sanguíneos/genética , Irmãos , Transfusão de Sangue
15.
Viruses ; 14(12)2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36560685

RESUMO

Experimental work with viruses that are highly pathogenic for humans and animals requires specialized Biosafety Level 3 or 4 facilities. Such pathogens include some spectacular but also rather seldomly studied examples such as Ebola virus (requiring BSL-4), more wide-spread and commonly studied viruses such as HIV, and the most recent example, SARS-CoV-2, which causes COVID-19. A common characteristic of these virus examples is that their genomes consist of single-stranded RNA, which requires the conversion of their genomes into a DNA copy for easy manipulation; this can be performed to study the viral life cycle in detail, develop novel therapies and vaccines, and monitor the disease course over time for chronic virus infections. We summarize the recent advances in such new genetic applications for RNA viruses in Switzerland over the last 25 years, from the early days of the HIV/AIDS epidemic to the most recent developments in research on the SARS-CoV-2 coronavirus. We highlight game-changing collaborative efforts between clinical and molecular disciplines in HIV research on the path to optimal clinical disease management. Moreover, we summarize how the modern technical evolution enabled the molecular studies of emerging RNA viruses, confirming that Switzerland is at the forefront of SARS-CoV-2 research and potentially other newly emerging viruses.


Assuntos
COVID-19 , Infecções por HIV , Vírus de RNA , Animais , Humanos , SARS-CoV-2/genética , Vírus de RNA/genética , Biologia Molecular
17.
Nat Commun ; 13(1): 7539, 2022 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-36477196

RESUMO

Large-scale intact glycopeptide identification has been advanced by software tools. However, tools for quantitative analysis remain lagging behind, which hinders exploring the differential site-specific glycosylation. Here, we report pGlycoQuant, a generic tool for both primary and tandem mass spectrometry-based intact glycopeptide quantitation. pGlycoQuant advances in glycopeptide matching through applying a deep learning model that reduces missing values by 19-89% compared with Byologic, MSFragger-Glyco, Skyline, and Proteome Discoverer, as well as a Match In Run algorithm for more glycopeptide coverage, greatly expanding the quantitative function of several widely used search engines, including pGlyco 2.0, pGlyco3, Byonic and MSFragger-Glyco. Further application of pGlycoQuant to the N-glycoproteomic study in three different metastatic HCC cell lines quantifies 6435 intact N-glycopeptides and, together with in vitro molecular biology experiments, illustrates site 979-core fucosylation of L1CAM as a potential regulator of HCC metastasis. We expected further applications of the freely available pGlycoQuant in glycoproteomic studies.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Biologia Molecular
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(6): 1637-1642, 2022 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-36476882

RESUMO

OBJECTIVE: To calculate the cut-off values of speed of platelet recovery and its R-squared in patients with acute myeloid leukemia (AML) after initial induction chemotherapy, which were used to predict the complete remission (CR) of the first induction chemotherapy, and guide the clinic to choose the next appropriate chemotherapy regimen as soon as possible. METHODS: A total of 117 patients with newly diagnosed AML in the Second Hospital of Shanxi Medical University were included. Patients were diagnosed by morphology, immunology, cytogenetics, and molecular biology (MICM) classification, and the risk stratification was evaluated in combination with the clinical situations of the patients at the time of admission. The peripheral platelet counts after the first induction chemotherapy were detected and the linear regression equation was used to calculate the recovery speed of platelet counts in 5 consecutive blood cell analysis before discharge. According to the ROC curve, the cut-off value between the recovery speed and the R-squared was calculated, and the cut-off value was used to divide the patients into different groups. The differences between groups were compared by Pearson χ2 test to observe the remission effect of the first induction chemotherapy. RESULTS: ROC curve analysis showed that the cut-off value for predicting the platelet recovery speed and its R-squared of the first induction chemotherapy to achieve remission was 4.059 5×109/(L·d) and 72.7%, the sensitivity was 77% and 63.9%, the specificity was 62.5% and 67.9%, and the Youden index was 0.395 and 0.318, respectively. The patients were divided into different groups and compared according to the above cut-off values, and the results showed statistical differences (P<0.001, P=0.001). CONCLUSION: The cut-off value of platelet recovery speed and its R-squared after the first induction chemotherapy calculated by peripheral platelet count and ROC curve in AML patients can be used as an index to evaluate the remission. The faster the platelet recovery speed after chemotherapy is, the more likely patients achieve remission. The more stable the platelet recovery tendency is, the more likely patients achieve remission too.


Assuntos
Quimioterapia de Indução , Leucemia Mieloide Aguda , Humanos , Citogenética , Leucemia Mieloide Aguda/tratamento farmacológico , Biologia Molecular
19.
Medicine (Baltimore) ; 101(48): e31941, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36482625

RESUMO

OBJECTIVE: To explore the potential mechanism of triptolide in diabetic nephropathy (DN) treatment using network pharmacology. METHODS: The main targets of triptolide were screened using the TCMSP, DrugBank, and NCBI databases, and gene targets of DN were searched using the DrugBank, DisGeNET, TTD, and OMIM databases. All of the above targets were normalized using the UniProt database to obtain the co-acting genes. The co-acting genes were uploaded to the STRING platform to build a protein-protein interaction network and screen the core acting targets. Gene ontology and Kyoto encyclopedia of genes and genomes analyses of the core targets were performed using Metascape. Molecular docking validation of triptolide with the co-acting genes was performed using the Swiss Dock platform. RESULTS: We identified 76 potential target points for triptolide, 693 target points for DN-related diseases, and 24 co-acting genes. The main pathways and biological processes involved are lipids and atherosclerosis, IL-18 signaling pathway, TWEAK signaling pathway, response to oxidative stress, hematopoietic function, and negative regulation of cell differentiation. Both triptolide and the active site of the core target genes can form more than 2 hydrogen bonds, and the bond energy is less than -5kJ/mol. Bioinformatics analysis showed that triptolide had a regulatory effect on most of the core target genes that are aberrantly expressed in DKD. CONCLUSION: Triptolide may regulate the body's response to cytokines, hormones, oxidative stress, and apoptosis signaling pathways in DN treatment by down-regulating Casp3, Casp8, PTEN, GSA3B and up-regulating ESR1, and so forth.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Fenantrenos , Humanos , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/genética , Simulação de Acoplamento Molecular , Fenantrenos/farmacologia , Fenantrenos/uso terapêutico , Biologia Molecular
20.
Adv Anat Embryol Cell Biol ; 235: 1-16, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36525107

RESUMO

The centrosome field has seen enormous progress during the past few decades which spans the large areas of cell biology with new information on cell cycle controls and cellular health; immunology with centrosomes being essential for the formation of the immunological synapse; neurobiology with new insights into centrosome dysfunctions leading to disorders and disease; stem cell biology with fate-determining distribution of centrosomal material during asymmetric cell division; cancer biology with huge insights into the role of centrosomes in disease initiation, progression, and manifestation; reproductive biology with essential centrosome functions in oocytes, during fertilization and embryo development in which centrosome dysfunctions can be related back to abnormal centrosomal material in the meiotic spindle of oocytes; and several others that will be highlighted in the specific chapters of this book.


Assuntos
Centrossomo , Fuso Acromático , Centrossomo/fisiologia , Oócitos/fisiologia , Desenvolvimento Embrionário , Biologia Molecular
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