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1.
Nature ; 575(7783): 494-499, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31723263

RESUMEN

In rapidly adapting asexual populations, including many microbial pathogens and viruses, numerous mutant lineages often compete for dominance within the population1-5. These complex evolutionary dynamics determine the outcomes of adaptation, but have been difficult to observe directly. Previous studies have used whole-genome sequencing to follow molecular adaptation6-10; however, these methods have limited resolution in microbial populations. Here we introduce a renewable barcoding system to observe evolutionary dynamics at high resolution in laboratory budding yeast. We find nested patterns of interference and hitchhiking even at low frequencies. These events are driven by the continuous appearance of new mutations that modify the fates of existing lineages before they reach substantial frequencies. We observe how the distribution of fitness within the population changes over time, and find a travelling wave of adaptation that has been predicted by theory11-17. We show that clonal competition creates a dynamical 'rich-get-richer' effect: fitness advantages that are acquired early in evolution drive clonal expansions, which increase the chances of acquiring future mutations. However, less-fit lineages also routinely leapfrog over strains of higher fitness. Our results demonstrate that this combination of factors, which is not accounted for in existing models of evolutionary dynamics, is critical in determining the rate, predictability and molecular basis of adaptation.


Asunto(s)
Adaptación Fisiológica/genética , Linaje de la Célula , Evolución Molecular , Laboratorios , Mutación , Saccharomyces cerevisiae/citología , Saccharomyces cerevisiae/genética , Células Clonales/citología , Células Clonales/metabolismo , Código de Barras del ADN Taxonómico , Aptitud Genética/genética
2.
Hum Reprod ; 39(8): 1673-1683, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38914481

RESUMEN

STUDY QUESTION: Is increasing the intensity of high-intensity focused ultrasound (HIFU) by 30% in the treatment of rectal endometriosis a safe procedure? SUMMARY ANSWER: This study demonstrates the safety of a 30% increase in the intensity of HIFU in the treatment of rectal endometriosis, with no Clavien-Dindo Grade III complications overall, and namely no rectovaginal fistulae. WHAT IS KNOWN ALREADY: A feasibility study including 20 patients with rectal endometriosis demonstrated, with no severe complications, a significant improvement in digestive disorders, dysmenorrhoea, dyspareunia, and health status, although the volume of the endometriosis nodule did not appear to be reduced. STUDY DESIGN, SIZE, DURATION: A prospective multicentre cohort study was conducted between 2020 and 2022 with 60 patients with symptomatic rectal endometriosis. Following the failure of medical treatment, HIFU treatment was offered as an alternative to surgery. PARTICIPANTS/MATERIALS, SETTING, METHODS: As the main objective of this study was to examine safety, all adverse events observed during the 6 months of follow-up were analysed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) and Clavien-Dindo classifications. Secondary objectives included evaluating the evolution of symptoms using validated questionnaires: gynaecological and digestive pain symptoms with a visual analogue scale, health status with the Medical Outcomes Study 36-item Short Form (SF-36) questionnaire, average post-operative daily pain level, and analgesic medication required in the 10 days following treatment. MRI was also performed at Day 1 to detect early complications. Finally, we performed a blinded MRI review of the evolution of the nodule at 6 months post-treatment. MAIN RESULTS AND THE ROLE OF CHANCE: The procedure was performed under spinal anaesthesia for 30% of the patients. The median duration of treatment was 32 min. Fifty-five patients left the hospital on Day 1. MRI scans performed on Day 1 did not highlight any early-onset post-operative complication. Using the Clavien-Dindo classification, we listed 56.7% Grade I events, 3.4% Grade II events, and no events Grade III or higher. At 1, 3, and 6 months, all gynaecologic, digestive and general symptoms, as well as health status, had significantly improved. The evolution of the nodule was also significant (P < 0.001) with a 28% decrease in volume. LIMITATIONS, REASONS FOR CAUTION: The main objective was safety and not effectiveness. The study was not randomized and there was no control group. WIDER IMPLICATIONS OF THE FINDINGS: HIFU treatment for rectal endometriosis results in an improvement of symptoms with low morbidity; as such, for selected patients, it could be a valuable alternative to surgical approaches following the failure of medical treatment. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the company EDAP TMS. Professors Dubernard and Rousset are consultants for EDAP TMS. Dubernard received travel support from EDAP-TMS. Dr F. Chavrier received industrial grants from EDAP-TMS. He has developed a device for generating focused ultrasonic waves with reduced treatment time. This device has been patented by EDAP-TMS. Dr Lafon received industrial grants from EDAP-TMS; he declares that EDAP-TMS provided funding directly to INSERM to support a young researcher chair in therapeutic ultrasound, which is unrelated to the current study. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT04494568.


Asunto(s)
Endometriosis , Enfermedades del Recto , Humanos , Femenino , Endometriosis/terapia , Endometriosis/cirugía , Endometriosis/diagnóstico por imagen , Adulto , Estudios Prospectivos , Enfermedades del Recto/terapia , Francia , Resultado del Tratamiento , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Ultrasonido Enfocado de Alta Intensidad de Ablación/efectos adversos , Persona de Mediana Edad , Dismenorrea/terapia , Dispareunia/etiología , Dispareunia/terapia
3.
Cell Mol Biol (Noisy-le-grand) ; 70(5): 1-9, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38814241

RESUMEN

Non-Hodgkin lymphoma (NHL) is a lymphoproliferative disorder derived from either B or T lymphocytes. Among NHL, activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) and T cell non-Hodgkin lymphomas (T-NHL) are poor prognosis and aggressive subtypes. Macrophages are professional phagocytic cells and dendritic cells (DCs) are professional antigen-presenting cells in immune system. Doxorubicin (Dox) and Etoposide (ET) are the most effective anti-cancer drugs. A20 and CYLD are negative regulators of NF-κB-dependent functions in many cell types. Little is known about the roles of A20 and CYLD in regulating functions of DCs and macrophages from NHL. The present study, therefore, explored whether A20/CYLD expression contributes to functions of DCs and macrophages from NHL. To this end, blood samples of seventy-nine patients with ABC DLBCL and T-NHL were examined. Gene expression profile was determined by quantitative RT-PCR and immunophenotype, cell apoptosis and phagocytosis by flow cytometry. As a result, immunophenotypic analysis showed that the numbers of CD13+CD117-, CD56+CD40+ and CD23+CD40+ expressing cells were significantly elevated in ABC DLBCL cases compared to healthy individuals and T-NHL patients. Interestingly, upon treatment of Dox and ET, the phagocytosis of lymphoma cells was significantly reduced by CD11c+CD123- DCs and the percentage of CD56+ mature DCs was significantly enhanced in ABC DLBCL patients only in the presence of A20 siRNA, but not CYLD siRNA. In conclusion, ABC DLBCL patients with low A20 expression were defective in elimination of lymphoma cells by DCs and linked to killer DC expansion in circulation.


Asunto(s)
Células Dendríticas , Linfoma de Células B Grandes Difuso , Fagocitosis , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa , Humanos , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Fagocitosis/efectos de los fármacos , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/metabolismo , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/genética , Femenino , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/inmunología , Persona de Mediana Edad , Masculino , Linfoma no Hodgkin/patología , Linfoma no Hodgkin/inmunología , Apoptosis/efectos de los fármacos , Anciano , Adulto , Macrófagos/metabolismo , Macrófagos/inmunología , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Linfocitos B/inmunología , Linfocitos B/metabolismo , Inmunofenotipificación
4.
J Minim Invasive Gynecol ; 31(2): 155-160, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37984516

RESUMEN

Epithelial ovarian and fallopian cancers are aggressive lesions that rarely metastasize to the central nervous system. Brain metastases usually occur in the setting of known primary disease or widespread metastatic disease. However, in extremely rare cases, an isolated intracranial neoplasm may be the first presentation of fallopian cancer. To the best of our knowledge, only one such case has been reported previously. We present an illustrative case with multimodality imaging and histopathologic correlation of a fallopian tube carcinoma first presenting with altered mental status secondary to an isolated brain metastasis. A 64-year-old female with no pertinent medical history presented with altered mentation. Initial workup identified a 1.6 cm avidly enhancing, solitary brain lesion at the gray-white junction with associated vasogenic edema concerning for either central nervous system lymphoma or metastatic disease. Additional imaging identified a 7.5 × 3 cm left adnexal lesion, initially thought to be a hydrosalpinx with hemorrhage, but magnetic resonance imaging suggested gynecologic malignancy. No lesions elsewhere in the body were identified. Given the lack of locoregional or systemic disease, the intracranial and pelvic lesions were assumed to represent synchronous but distinct processes. The intracranial lesion was biopsied. Preliminary results were suggestive of lymphoma, but further analysis was consistent with high-grade serous carcinoma of müllerian origin. Positron emission tomography/computed tomography was performed to evaluate for other neoplastic lesions, only highlighting the intracranial and pelvic lesions. At this point, a diagnosis of metastatic fallopian cancer was made. The patient was taken for robot-assisted laparoscopy with surgical debulking of the pelvic neoplasm, pathology demonstrating high-grade serous carcinoma of the fallopian tube, matching that of the intracranial lesion. Even though rare, metastatic fallopian cancer should be considered in patients with isolated brain lesions and adnexal lesions, even in the absence of locoregional or systemic disease.


Asunto(s)
Neoplasias Encefálicas , Carcinoma , Neoplasias de las Trompas Uterinas , Linfoma , Neoplasias Ováricas , Humanos , Femenino , Persona de Mediana Edad , Trompas Uterinas/cirugía , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/patología , Neoplasias de las Trompas Uterinas/cirugía , Neoplasias de las Trompas Uterinas/patología , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Encéfalo , Linfoma/patología
5.
J Pharmacol Exp Ther ; 386(3): 277-287, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37024146

RESUMEN

Pulmonary fibroblasts are the primary producers of extracellular matrix (ECM) in the lungs, and their pathogenic activation drives scarring and loss of lung function in idiopathic pulmonary fibrosis (IPF). This uncontrolled production of ECM is stimulated by mechanosignaling and transforming growth factor beta 1 (TGF-ß1) signaling that together promote transcriptional programs including Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). G protein-coupled receptors (GPCRs) that couple to G α s have emerged as pharmacological targets to inactivate YAP/TAZ signaling and promote lung fibrosis resolution. Previous studies have shown a loss of expression of "antifibrotic GPCRs"-receptors that couple to G α s, in IPF patient-derived fibroblasts compared with non-IPF samples. Of the 14 G α s GPCRs we found to be expressed in lung fibroblasts, the dopamine receptor D1 (DRD1) was one of only two not repressed by TGF-ß1 signaling, with the ß2-adrenergic receptor being the most repressed. We compared the potency and efficacy of multiple D1 and ß2 receptor agonists +/- TGF-ß1 treatment in vitro for their ability to elevate cAMP, inhibit nuclear localization of YAP/TAZ, regulate expression of profibrotic and antifibrotic genes, and inhibit cellular proliferation and collagen deposition. Consistently, the activity of ß2 receptor agonists was lost, whereas D1 receptor agonists was maintained, after stimulating cultured lung fibroblasts with TGF-ß1. These data further support the therapeutic potential of the dopamine receptor D1 and highlight an orchestrated and pervasive loss of antifibrotic GPCRs mediated by TGF-ß1 signaling. SIGNIFICANCE STATEMENT: Idiopathic pulmonary fibrosis (IPF) is a deadly lung disease with limited therapies. GPCRs have emerged as a primary target for the development of novel antifibrotic drugs; however, a challenge to this approach is the dramatic changes in GPCR expression in response to profibrotic stimuli. Here, we investigate the impact of TGF-ß1 on the expression of antifibrotic GPCRs and show the D1 dopamine receptor expression is uniquely maintained in response to TGF-ß1, further implicating it as a compelling target to treat IPF.


Asunto(s)
Fibrosis Pulmonar Idiopática , Factor de Crecimiento Transformador beta1 , Humanos , Fibroblastos/metabolismo , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/metabolismo , Fibrosis Pulmonar Idiopática/patología , Pulmón , Receptores Dopaminérgicos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo
6.
Radiographics ; 43(3): e220097, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36821510

RESUMEN

Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated fibrosclerosing disease with tumefactive lesions infiltrated by IgG4-positive plasma cells. Initially described as autoimmune pancreatitis, IgG4-RD is now recognized as a discrete entity and is found to affect virtually any organ in the body. Common extrapancreatic sites include the biliary tree, salivary glands, periorbital tissue, lungs, kidneys, lymph nodes, aorta, retroperitoneum, and thyroid gland. Diagnosis-which relies on histopathologic, serologic, and radiologic features-can be challenging with the disease underdiagnosed, as IgG4-RD often mimics malignancy, infectious processes, or other immune-mediated conditions. Patients may present with signs of compression of nearby structures due to mass effect or with organ failure when the disease is left untreated. The clinical course is complex, with single- or multiorgan involvement and metachronous or synchronous occurrence of lesions. IgG4-RD responds well to glucocorticoid therapy, disease-modifying antirheumatic drugs, and B-cell-depleting biologic agents; prompt diagnosis is important to avoid delay in treatment and unnecessary pharmacologic or surgical intervention. While imaging features may not be specific for IgG4-RD, functional whole-body imaging with fluorine 18-fluorodeoxyglucose PET/CT is a useful adjunct for localizing extrapancreatic sites for biopsy, monitoring therapeutic response, and demonstrating disease relapse. The authors describe the pancreatic and extrapancreatic sites of involvement in IgG4-RD, with imaging features and patterns to aid in distinguishing IgG4-RD from its mimics through a multimodality approach with emphasis on functional imaging evaluation. ©RSNA, 2023 Quiz questions in the supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.


Asunto(s)
Enfermedades Autoinmunes , Enfermedad Relacionada con Inmunoglobulina G4 , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Inmunoglobulina G , Páncreas
7.
Environ Res ; 216(Pt 1): 114342, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36181894

RESUMEN

Plastics, micro- and nano-plastics pollution are undoubtedly a severe and crucial ecological threat due to the durability of plastics and their destructive impacts on humans and wildlife. Most scientific investigations have addressed the classification, types, distribution, ingestion, fate, impacts, degradation, and various adverse effect of plastics. Heretofore, scanty reports have addressed implementing strategies for the remediation and mitigation of plastics. Therefore, in this paper, we review the current studies on the degradation of plastics, micro- and nano-plastics aided by microorganisms, and explore the relevant degradation properties and mechanisms. Diverse microorganisms are classified, such as bacteria, fungi, algae, cyanobacteria, wax worms, and enzymes that can decompose various plastics. Furthermore, bio-degradation is influenced by microbial features and environmental parameters; therefore, the ecological factors affecting plastic degradation and the resulting degradation consequences are discussed. In addition, the mechanisms underlying microbial-mediated plastic degradation are carefully studied. Finally, upcoming research directions and prospects for plastics degradation employing microorganisms are addressed. This review covers a comprehensive overview of the microorganism-assisted degradation of plastics, micro- and nano-plastics, and serves as a resource for future research into sustainable plastics pollution management methods.


Asunto(s)
Contaminantes Ambientales , Contaminantes Químicos del Agua , Humanos , Contaminantes Ambientales/toxicidad , Contaminantes Ambientales/metabolismo , Microplásticos/toxicidad , Contaminación Ambiental , Hongos , Biotecnología , Biodegradación Ambiental , Contaminantes Químicos del Agua/metabolismo
8.
Ecotoxicol Environ Saf ; 255: 114793, 2023 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-36963189

RESUMEN

In this work, we develop a mussel-inspired biosorbent combined with graphene oxide for removal of organic dyes in water sources. The composite was prepared via self-polymerization of dopamine in weak alkaline solution containing graphene oxide at ambient condition. Morphological and structural studies revealed that polydopamine has gradually grown to cover the surface of graphene oxide flakes, partially reduced these flakes, and somehow form many grains (size around 20 nm) on the flakes instead of making very large aggregates as usual. The mass ratio between two components of the composite was also investigated to find the optimal one which provides enough surface area (20 m2.g-1) and maintain adhesive sites in order to ensure high-efficiency removal of organic molecules. The adsorption kinetics and isotherms of as-prepared adsorbent towards methylene blue were found to fit well with pseudo-first order kinetics model and Langmuir isotherm. The maximum adsorption capacity (qm) and Langmuir constant (kL) were estimated to be 270 mg.g-1 and 0.49 L. mg-1. The as-prepared bio-sorbent is very promising for remediation of water sources contaminated with cationic organic molecules and heavy metal ions.


Asunto(s)
Contaminantes Ambientales , Grafito , Metales Pesados , Contaminantes Químicos del Agua , Agua , Grafito/química , Adsorción , Contaminantes Químicos del Agua/análisis , Cinética , Azul de Metileno/química
9.
Plant Mol Biol ; 109(3): 233-248, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32902791

RESUMEN

KEY MESSAGE: The field survey in this article showed in 'KU50', a popular variety and late-branching type of cassava in Southeast Asia, that flowering rarely occurs in normal-field conditions in Southeast Asia but is strongly induced in the dry season in the mountainous region. Flowering time is correlated with the expression patterns of MeFT1 and homologs of Arabidopsis GI, PHYA, and NF-Ys. Cassava (Manihot esculenta Crantz) is a tropical crop that is propagated vegetatively rather than sexually by seed. Flowering rarely occurs in the erect-type variety grown in Southeast Asia, but it is known that cassava produces flowers every year in mountainous regions. Data pertaining to the effect of environmental factors on flowering time and gene expression in cassava, however, is limited. The aim of the present study was to determine the kinds of environmental conditions that regulate flowering time in cassava and the underlying molecular mechanisms. The flowering status of KU50, a popular variety in Southeast Asia and late-branching type of cassava, was monitored in six fields in Vietnam and Cambodia. At non-flowering and flowering field locations in North Vietnam, the two FLOWERING LOCUS T (FT)-like genes, MeFT1 and MeFT2, were characterized by qPCR, and the pattern of expression of flowering-related genes and genes responsive to environmental signals were analyzed by using RNA sequencing data from time-series samples. Results indicate that cassava flowering was induced in the dry season in the mountain region, and that flowering time was correlated with the expression of MeFT1, and homologs of Arabidopsis GI, PHYA, and NF-Ys. Based upon these data, we hypothesize that floral induction in cassava is triggered by some conditions present in the mountain regions during the dry season.


Asunto(s)
Arabidopsis , Manihot , Arabidopsis/genética , Arabidopsis/metabolismo , Asia Sudoriental , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Manihot/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
10.
Anal Biochem ; 654: 114799, 2022 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-35780814

RESUMEN

The missense mutation EGFR L858R implies increased sensitivity to EGFR tyrosine kinase inhibitor (TKIs) therapy, despite a significant non-response rate. Currently, detection of EGFR L858R mutation is mostly DNA based, therefore, the allele-specific expression level of the mutated gene and its clinical relevance is hidden. Based on the extendable blocking probes and hot-start protocol for reverse transcription, we have developed and validated a novel one-step realtime RT-PCR assay that enables detection of EGFR L858R mutation at the mRNA level. This RNA-based assay was able to detect the EGFR L858R mutation in a 10,000-fold excess of its wildtype counterpart, indicating an analytical sensitivity of 0.01%. In comparison to the reference DNA-based assay, the RNA-based assay further detected the EGFR L858R mutation in significantly additional formalin-fixed paraffin-embedded (FFPE) samples (19.2% vs 15.0%). Interestingly, our data showed that the relative mRNA levels of EGFR L858R mutation varied greatly in tumor tissues (∼4 logs); and the circulating mRNA of EGFR L858R mutation was detectable in plasma of NSCLC patients. This novel RNA-based PCR assay provides a simple and ultrasensitive tool for detection of EGFR L858R mutation at the mRNA level as a new class of biomarkers.


Asunto(s)
Receptores ErbB , Neoplasias Pulmonares , ADN , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/genética , Mutación , Inhibidores de Proteínas Quinasas , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa
11.
PLoS Biol ; 17(3): e3000182, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30925180

RESUMEN

In experimental evolution, scientists evolve organisms in the lab, typically by challenging them to new environmental conditions. How best to evolve a desired trait? Should the challenge be applied abruptly, gradually, periodically, sporadically? Should one apply chemical mutagenesis, and do strains with high innate mutation rate evolve faster? What are ideal population sizes of evolving populations? There are endless strategies, beyond those that can be exposed by individual labs. We therefore arranged a community challenge, Evolthon, in which students and scientists from different labs were asked to evolve Escherichia coli or Saccharomyces cerevisiae for an abiotic stress-low temperature. About 30 participants from around the world explored diverse environmental and genetic regimes of evolution. After a period of evolution in each lab, all strains of each species were competed with one another. In yeast, the most successful strategies were those that used mating, underscoring the importance of sex in evolution. In bacteria, the fittest strain used a strategy based on exploration of different mutation rates. Different strategies displayed variable levels of performance and stability across additional challenges and conditions. This study therefore uncovers principles of effective experimental evolutionary regimens and might prove useful also for biotechnological developments of new strains and for understanding natural strategies in evolutionary arms races between species. Evolthon constitutes a model for community-based scientific exploration that encourages creativity and cooperation.


Asunto(s)
Evolución Biológica , Escherichia coli/metabolismo , Humanos , Modelos Genéticos , Mutación/genética , Saccharomyces cerevisiae/metabolismo , Temperatura
12.
Cell Mol Biol (Noisy-le-grand) ; 68(10): 47-53, 2022 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-37114273

RESUMEN

Chronic myelogenous leukemia (CML) is characterised by the translocation of regions of the BCR and ABL genes, leading to the fusion gene BCR-ABL forming the Philadelphia (Ph) chromosome. Vinblastine (Vinb) and Vincristine (Vinc) are Vinca alkaloids and frequently used in combination chemotherapy in leukemias and lymphomas. Deubiquitinating enzyme (DUB) genes such as A20, Otubain 1 and CYLD are known as inhibitors of functional activation of immune cells mediated through the NF-κB/STAT pathway. Little is known about the regulatory role of Vinb/Vinc on the function of CML cells and the contribution of the DUBs to those effects. In the end, the gene expression profile was determined by quantitative RT-PCR, physiological properties of CML cells by flow cytometry and cytokine production by ELISA. As a result, inactivated expression of the DUBs A20, CYLD, Otubain 1 and Cezanne and enhanced activation of CD11b+ and CD4T cells were observed in CML patients. Importantly, Vinc enhanced the expression of A20 and CYLD and inhibited the proliferation and survival of CML (K562) cells. The effects were abolished in the presence of A20 siRNA, while cell proliferation only depended on the presence of CYLD. In conclusion, the up-regulation of A20 by Vinc could involve inhibitory effects on the proliferation and survival of K562 cells. The events might contribute to the anticancer effect of Vinc on A20-sensitive CML cells.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva , Vinblastina , Humanos , Enzima Desubiquitinante CYLD/genética , Proteínas de Fusión bcr-abl/genética , Expresión Génica , Células K562 , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Vinblastina/farmacología , Vinblastina/uso terapéutico , Vincristina/farmacología
13.
Int J Immunogenet ; 49(5): 340-344, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35916345

RESUMEN

Human leucocyte antigen (HLA) alleles are very diverse and characterized by ethnicity. To date, information about the frequencies and distributions of HLA alleles among the Vietnamese population is still limited. In this study, HLA-DQB1 alleles of 2076 cord blood units from individuals belonging to Vietnam's Kinh ethnic people were genotyped using Luminex-based polymerase chain reaction sequence-specific oligonucleotide. The results of the study demonstrated that there were 23 alleles on the locus HLA-DQB1. Among those, there were six alleles with high frequencies of over 5%, including DQB1* 03:01 (35.9%), DQB1* 05:01 (12.8%), DQB1* 03:03 (12.2%); DQB1* 06:01 (7.20%), DQB1* 05:02 (6.62%) and DQB1* 02:01 (5.30%) and five rare alleles with low frequencies of below 0.1%. More importantly, this study for the first time reported the presence of two new rare alleles including DQB1* 01:01 and DQB1* 01:02. Conclusively, this study provided significant information about HLA-DQB1 alleles for further investigations and clinical applications.


Asunto(s)
Pueblo Asiatico , Sangre Fetal , Alelos , Pueblo Asiatico/genética , Frecuencia de los Genes , Cadenas beta de HLA-DQ/genética , Cadenas HLA-DRB1/genética , Haplotipos , Humanos , Vietnam
14.
PLoS Genet ; 15(2): e1007958, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30768593

RESUMEN

Screens for epistatic interactions have long been used to characterize functional relationships corresponding to protein complexes, metabolic pathways, and other functional modules. Although epistasis between adaptive mutations is also common in laboratory evolution experiments, the functional basis for these interactions is less well characterized. Here, we quantify the extent to which gene function (as determined by a genome-wide screen for epistasis among deletion mutants) influences the rate and genetic basis of compensatory adaptation in a set of 37 gene deletion mutants nested within 16 functional modules. We find that functional module has predictive power: mutants with deletions in the same module tend to adapt more similarly, on average, than those with deletions in different modules. At the same time, initial fitness also plays a role: independent of the specific functional modules involved, adaptive mutations tend to be systematically more beneficial in less-fit genetic backgrounds, consistent with a general pattern of diminishing returns epistasis. We measured epistatic interactions between initial gene deletion mutations and the mutations that accumulate during compensatory adaptation and found a general trend towards positive epistasis (i.e. mutations tend to be more beneficial in the background in which they arose). In two functional modules, epistatic interactions between the initial gene deletions and the mutations in their descendant lines caused evolutionary entrenchment, indicating an intimate functional relationship. Our results suggest that genotypes with similar epistatic interactions with gene deletion mutations will also have similar epistatic interactions with adaptive mutations, meaning that genome scale maps of epistasis between gene deletion mutations can be predictive of evolutionary dynamics.


Asunto(s)
Epistasis Genética , Evolución Molecular , Eliminación de Gen , Adaptación Fisiológica/genética , Simulación por Computador , Genes Fúngicos , Aptitud Genética , Redes y Vías Metabólicas/genética , Modelos Genéticos , Mutación , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo
15.
J Card Surg ; 37(9): 2849-2851, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35502494

RESUMEN

Cardiac hemangioma is a rare, benign primary tumor characterized by endothelial proliferation. While reports of cardiac hemangiomas demonstrating 18 F FDG avidity and other forms of hemangiomas showing 68 Ga Dotatate avidity have been published, we present a rare case of primary cardiac hemangioma demonstrating 68 Ga Dotatate avidity, mimicking a primary neuroendocrine tumor.


Asunto(s)
Neoplasias Cardíacas , Hemangioma , Tumores Neuroendocrinos , Fluorodesoxiglucosa F18 , Neoplasias Cardíacas/diagnóstico por imagen , Neoplasias Cardíacas/cirugía , Hemangioma/diagnóstico por imagen , Hemangioma/cirugía , Humanos , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/cirugía , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones , Cintigrafía , Radiofármacos
16.
Trends Genet ; 34(9): 693-703, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30025666

RESUMEN

Evolutionary dynamics in laboratory microbial evolution experiments can be surprisingly complex. In the past two decades, observations of these dynamics have challenged simple models of adaptation and have shown that clonal interference, hitchhiking, ecological diversification, and contingency are widespread. In recent years, advances in high-throughput strain maintenance and phenotypic assays, the dramatically reduced cost of genome sequencing, and emerging methods for lineage barcoding have made it possible to observe evolutionary dynamics at unprecedented resolution. These new methods can now begin to provide detailed measurements of key aspects of fitness landscapes and of evolutionary outcomes across a range of systems. These measurements can highlight challenges to existing theoretical models and guide new theoretical work towards the complications that are most widely important.


Asunto(s)
Adaptación Fisiológica/genética , Bacterias/genética , Evolución Molecular Dirigida , Aptitud Genética/genética , Bacterias/crecimiento & desarrollo , Secuenciación de Nucleótidos de Alto Rendimiento
17.
Radiographics ; 41(2): 576-594, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33606566

RESUMEN

Histiocytosis is a rare inflammatory process characterized by pathologic infiltration and accumulation of cells derived from the monocytic lineage in normal tissue. It encompasses more than 100 different subtypes of disorders that were recently classified into five main groups: (a) Langerhans-related histiocytosis, (b) Rosai-Dorfman histiocytosis, (c) cutaneous and mucocutaneous histiocytosis, (d) malignant histiocytosis, and (e) hemophagocytic lymphohistiocytosis and macrophage activation syndrome. Langerhans cell histiocytosis is the most common histiocytic disorder. Less common types include Erdheim-Chester disease, Rosai-Dorfman disease, adult and juvenile xanthogranuloma, necrobiotic xanthogranuloma, histiocytic sarcoma, interdigitating dendritic cell sarcoma, Langerhans cell sarcoma, and hemophagocytic lymphohistiocytosis. Although the pathogenesis of these disorders may be attributable to mutations in the oncogenic driver, recent discoveries have shown that inflammation and fibrosis secondary to mutated histiocytes, rather than a proliferative cell mechanism, result in manifestation of the disease. Diagnosis, which relies on a multidisciplinary approach, is challenging and often delayed because clinical findings are nonspecific and may mimic malignant processes at radiologic evaluation. Compared with conventional imaging, PET/CT allows detection of the increased metabolic activity in histiocytes. Diagnostic algorithms for histiocytic disorders should include functional imaging with fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT, which provides a comprehensive whole-body evaluation of their potential involvement with multiple organ systems and allows monitoring of therapeutic response. The most recent revised classification, pathophysiologic and clinical manifestations, sites of involvement, and imaging features of histiocytosis are described in this review and a multimodality approach is used, with emphasis on 18F-FDG PET/CT evaluation. ©RSNA, 2021.


Asunto(s)
Histiocitosis de Células de Langerhans , Histiocitosis Sinusal , Histiocitosis , Neoplasias , Células Dendríticas , Histiocitosis/diagnóstico por imagen , Histiocitosis de Células de Langerhans/diagnóstico por imagen , Histiocitosis Sinusal/diagnóstico por imagen , Humanos , Macrófagos , Imagen Multimodal , Tomografía Computarizada por Tomografía de Emisión de Positrones
18.
Sensors (Basel) ; 21(16)2021 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-34451069

RESUMEN

In practice, self-interference (SI) in full-duplex (FD) wireless communication systems cannot be completely eliminated due to imperfections in different factors, such as the SI channel estimation and hardware circuits. Therefore, residual SI (RSI) always exists in FD systems. In addition, hardware impairments (HIs) cannot be avoided in FD systems due to the non-ideal characteristics of electronic components. These issues motivate us to consider an FD-HI system with a decode-and-forward (DF) relay that is applied for vehicle-to-vehicle (V2V) communication. Unlike previous works, the performance of the proposed FD-HI-V2V system is evaluated over cascaded Rayleigh fading channels (CRFCs). We mathematically obtain the exact closed-form expressions of the outage probability (OP), system throughput (ST), and ergodic capacity (EC) of the proposed FD-HI-V2V system under the joint and crossed effects of the RSI, HIs, and CRFCs. We validate all derived expressions via Monte-Carlo simulations. Based on these expressions, the OP, ST, and EC of the proposed FD-HI-V2V system are investigated and compared with other related systems, such as ideal hardware (ID) and half-duplex (HD) systems, as well as a system over traditional Rayleigh fading channels (RFCs), to clearly show the impacts of negative factors.


Asunto(s)
Redes de Comunicación de Computadores , Computadores , Simulación por Computador , Método de Montecarlo , Probabilidad
19.
J Synchrotron Radiat ; 27(Pt 5): 1372-1375, 2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-32876614

RESUMEN

The pressure effects on atomic mean-square relative displacement characterizing the extended X-ray absorption fine structure (EXAFS) Debye-Waller factor of iron metal have been investigated based on the Debye model. The analytical expressions of the Debye frequency and EXAFS Debye-Waller factor have been derived as functions of crystal volume compressibility. Based on the well established equation-of-state including the contributions of the anharmonic and electronic thermal pressures, numerical calculations have been performed for iron up to a pressure of 220 GPa and compared with experimental data when possible. These results show that the Debye frequency increases rapidly with compression, and beyond 150 GPa it behaves as a linear function of pressure. Meanwhile the mean-square relative displacement curve drops robustly with pressure, especially at pressures smaller than 100 GPa. This phenomenon causes the enhancement of EXAFS signals at high pressure. Reversely, the increasing of temperature will reduce the amplitude of EXAFS spectra.

20.
Opt Lett ; 45(7): 1611-1614, 2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-32235955

RESUMEN

In this Letter, the development of a custom-designed incoherent broadband cavity enhanced absorption spectrometer (IBBCEAS) and its application to in situ measurement of aerosol extinction near the ground surface are described in an effort to address the issue of missing data in the light detection and ranging (lidar) blind zone in the first hundreds of meters of the observation range. Combined measurements of aerosol extinction at the same location using lidar remote sensing at 355 nm and in situ IBBCEAS operating in the UV spectral region around 370 nm showed results with a good correlation (${{\rm R}^2} = {0.90}$R2=0.90) between the two measurement techniques. This Letter highlights a new strategy for near-end lidar calibration, using a ground-based compact and robust IBBCEAS located at the lidar measurement site to determine the vertical profile of the aerosol extinction coefficient with a higher accuracy.

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