Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 501
Filtrar
1.
Mol Cell ; 81(20): 4176-4190.e6, 2021 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-34529927

RESUMEN

Of the eight distinct polyubiquitin (polyUb) linkages that can be assembled, the roles of K48-linked polyUb (K48-polyUb) are the most established, with K48-polyUb modified proteins being targeted for degradation. MINDY1 and MINDY2 are members of the MINDY family of deubiquitinases (DUBs) that have exquisite specificity for cleaving K48-polyUb, yet we have a poor understanding of their catalytic mechanism. Here, we analyze the crystal structures of MINDY1 and MINDY2 alone and in complex with monoUb, di-, and penta-K48-polyUb, identifying 5 distinct Ub binding sites in the catalytic domain that explain how these DUBs sense both Ub chain length and linkage type to cleave K48-polyUb chains. The activity of MINDY1/2 is inhibited by the Cys-loop, and we find that substrate interaction relieves autoinhibition to activate these DUBs. We also find that MINDY1/2 use a non-canonical catalytic triad composed of Cys-His-Thr. Our findings highlight multiple layers of regulation modulating DUB activity in MINDY1 and MINDY2.


Asunto(s)
Enzimas Desubicuitinizantes/metabolismo , Poliubiquitina/metabolismo , Ubiquitina Tiolesterasa/metabolismo , Sitios de Unión , Dominio Catalítico , Cristalografía , Enzimas Desubicuitinizantes/genética , Activación Enzimática , Humanos , Cinética , Modelos Moleculares , Mutación , Unión Proteica , Conformación Proteica , Dispersión del Ángulo Pequeño , Relación Estructura-Actividad , Ubiquitina Tiolesterasa/genética , Ubiquitinación
2.
Mol Cell ; 70(1): 150-164.e6, 2018 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-29576527

RESUMEN

Deubiquitinating enzymes (DUBs) are important regulators of ubiquitin signaling. Here, we report the discovery of deubiquitinating activity in ZUFSP/C6orf113. High-resolution crystal structures of ZUFSP in complex with ubiquitin reveal several distinctive features of ubiquitin recognition and catalysis. Our analyses reveal that ZUFSP is a novel DUB with no homology to any known DUBs, leading us to classify ZUFSP as the seventh DUB family. Intriguingly, the minimal catalytic domain does not cleave polyubiquitin. We identify two ubiquitin binding domains in ZUFSP: a ZHA (ZUFSP helical arm) that binds to the distal ubiquitin and an atypical UBZ domain in ZUFSP that binds to polyubiquitin. Importantly, both domains are essential for ZUFSP to selectively cleave K63-linked polyubiquitin. We show that ZUFSP localizes to DNA lesions, where it plays an important role in genome stability pathways, functioning to prevent spontaneous DNA damage and also promote cellular survival in response to exogenous DNA damage.


Asunto(s)
Núcleo Celular/enzimología , Daño del ADN , Enzimas Desubicuitinizantes/metabolismo , Inestabilidad Genómica , Poliubiquitina/metabolismo , Sitios de Unión , Supervivencia Celular , Enzimas Desubicuitinizantes/química , Enzimas Desubicuitinizantes/genética , Células HEK293 , Células HeLa , Humanos , Células Jurkat , Lisina , Unión Proteica , Conformación Proteica , Dominios y Motivos de Interacción de Proteínas , Relación Estructura-Actividad , Especificidad por Sustrato , Ubiquitinación
3.
Oncologist ; 29(10): 842-849, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-38906704

RESUMEN

INTRODUCTION: Early discontinuation of endocrine therapy (ET) is higher among patients with early breast cancer (EBC) compared to patients with metastatic hormone receptor-positive (HR+) breast cancer (MBC). In our clinical experience the reasons for this may include a significant burden of ET side effects impacting quality of life (QOL) in patients with EBC. We hypothesized that QOL is lower in patients with HR + EBC compared to patients with HR + MBC on ET. METHODS: We conducted a cross-sectional observational study to assess QOL utilizing FACT-ES & EORTC QLQ C30 tools among patients with EBC and MBC receiving ET across 5 Irish hospitals. RESULTS: A total of 417 patients were enrolled-EBC (79% n = 331) and MBC 21% (n = 86). Using the FACT-ES, we found no difference in overall QOL by stage (139.2 vs 141, P  = .33). Patients with HR + MBC had a lower symptom burden from ET compared to HR + EBC (61.4 vs 54, P < .01). In adjusted multivariate linear regression models, there was no difference in QOL for patients with EBC and MBC receiving ET. CONCLUSIONS: There was no significant difference in overall QOL for patients with EBC and MBC. However, patients with EBC experienced more endocrine symptoms. In adjusted multivariate linear regression models, the stage did not predict QOL. Our results suggest that endocrine symptoms are significant contributors to impaired QOL for patients with EBC but the role of other determinants of QOL (eg, stage) is less clear. Future work could include the development of stage-specific QOL tools and utilization of electronic patient-reported outcomes (ePROs) to identify and manage emergent toxicities.


Asunto(s)
Neoplasias de la Mama , Calidad de Vida , Receptor ErbB-2 , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/psicología , Neoplasias de la Mama/patología , Persona de Mediana Edad , Estudios Transversales , Receptor ErbB-2/metabolismo , Anciano , Antineoplásicos Hormonales/uso terapéutico , Antineoplásicos Hormonales/efectos adversos , Adulto , Receptores de Estrógenos/metabolismo , Metástasis de la Neoplasia , Estadificación de Neoplasias , Receptores de Progesterona/metabolismo
4.
Bioinformatics ; 39(11)2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37847663

RESUMEN

SUMMARY: T-cell receptors (TCRs) on T cells recognize and bind to epitopes presented by the major histocompatibility complex in case of an infection or cancer. However, the high diversity of TCRs, as well as their unique and complex binding mechanisms underlying epitope recognition, make it difficult to predict the binding between TCRs and epitopes. Here, we present the utility of transformers, a deep learning strategy that incorporates an attention mechanism that learns the informative features, and show that these models pre-trained on a large set of protein sequences outperform current strategies. We compared three pre-trained auto-encoder transformer models (ProtBERT, ProtAlbert, and ProtElectra) and one pre-trained auto-regressive transformer model (ProtXLNet) to predict the binding specificity of TCRs to 25 epitopes from the VDJdb database (human and murine). Two additional modifications were performed to incorporate gene usage of the TCRs in the four transformer models. Of all 12 transformer implementations (four models with three different modifications), a modified version of the ProtXLNet model could predict TCR-epitope pairs with the highest accuracy (weighted F1 score 0.55 simultaneously considering all 25 epitopes). The modification included additional features representing the gene names for the TCRs. We also showed that the basic implementation of transformers outperformed the previously available methods, i.e. TCRGP, TCRdist, and DeepTCR, developed for the same biological problem, especially for the hard-to-classify labels. We show that the proficiency of transformers in attention learning can be made operational in a complex biological setting like TCR binding prediction. Further ingenuity in utilizing the full potential of transformers, either through attention head visualization or introducing additional features, can extend T-cell research avenues. AVAILABILITY AND IMPLEMENTATION: Data and code are available on https://github.com/InduKhatri/tcrformer.


Asunto(s)
Epítopos de Linfocito T , Receptores de Antígenos de Linfocitos T , Humanos , Animales , Ratones , Epítopos de Linfocito T/metabolismo , Receptores de Antígenos de Linfocitos T/genética , Linfocitos T/metabolismo , Secuencia de Aminoácidos , Complejo Mayor de Histocompatibilidad
5.
J Vasc Interv Radiol ; 35(2): 185-197, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38272639

RESUMEN

Thermal ablation modalities (cryoablation, radiofrequency ablation, and microwave ablation) have long been noted to occasionally induce a systemic antitumoral response. With the widespread use of checkpoint inhibitors, there is a significant interest in whether thermal ablation can promote immune system tumor recognition and increase checkpoint inhibitor response rates. In this review, we examine the current state of preclinical and clinical evidence examining the combination of checkpoint inhibitor therapies and thermal ablation modalities as well as discuss remaining the unanswered questions and directions for future research.


Asunto(s)
Criocirugía , Neoplasias , Ablación por Radiofrecuencia , Humanos , Neoplasias/terapia , Inmunoterapia/efectos adversos , Criocirugía/efectos adversos , Ablación por Radiofrecuencia/efectos adversos , Terapia Combinada
6.
Hepatol Res ; 2024 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-39340746

RESUMEN

AIM: Refractory ascites from portal hypertension can be managed with regular large-volume paracentesis (LVP) or transjugular intrahepatic portosystemic shunt (TIPS). Large-volume paracentesis is clinically unsatisfactory and many patients are ineligible or relatively contraindicated for TIPS or Denver shunt. Proximal splenic artery embolization (PSAE) using coils or plugs reduces but does not completely stop splenic arterial inflow, differing from distal splenic artery embolization techniques. By reducing splenic arterial inflow, splenic vein outflow is also decreased, lowering portal pressure and thus treating refractory ascites. METHODS: In this institutional review board-approved single-center retrospective study, electronic medical records were reviewed to obtain demographics and baseline clinical and laboratory data, paracentesis data before and after PSAE, PSAE procedural details, and follow-up imaging up to 12 months post-PSAE. Mixed-effects models were used for statistical analysis. RESULTS: Ten patients with LVP-dependent ascites meeting inclusion criteria underwent PSAE for refractory ascites from 2017 to 2024. Prior to PSAE, four patients had TIPS, three had liver transplants, and the remaining three were neither TIPS nor transplant candidates. In the month before PSAE, patients averaged 3.8 ± 1.7 paracentesis sessions, draining a total of 20.84 ± 10.39 L of fluid monthly. Post-PSAE, the number of paracentesis sessions decreased to 2.1 ± 2.7, 1.0 ± 1.7, 0.4 ± 1.1, and 0.0 ± 0.0 at 1, 3, 6, and 12 months, respectively (p = 0.03). Corresponding ascitic volume drained decreased to 8.7 ± 10.3, 2.7 ± 6.4, 2.0 ± 5.4, and 0.0 ± 0.0 L (p = 0.01). Over the 12-month follow-up period, 6 of 10 patients became LVP-independent. CONCLUSION: Proximal splenic artery embolization can improve refractory ascites in certain patients with portal hypertension, thus providing safe and effective treatment as an alternative to TIPS.

7.
Support Care Cancer ; 32(8): 515, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39012405

RESUMEN

This meta-analysis examined the effectiveness of exercise interventions in reducing fatigue and depression among women undergoing chemotherapy for breast cancer. The study followed PRISMA guidelines and analysed seven randomized controlled trials between 2016 and 2022. The results showed that exercise can substantially reduce fatigue levels (MD: -0.40, CI: -0.66, -0.14, P: 0.003), a common side effect of chemotherapy. Although depression did not significantly change (MD: -0.39, CI: -0.98, 0.20, P: 0.19), this study highlights the positive impact of exercise on mental health outcomes. The control group also experienced decreased quality of life (MD: 0.18, CI: 0.01-0.35, P: 0.03), emphasizing the importance of incorporating exercise interventions to improve overall well-being during breast cancer treatment. In addition to primary outcomes, the study revealed that exercise positively affected secondary aspects such as cognitive fatigue, social function, physical function, constipation, and dyspnoea.


Asunto(s)
Neoplasias de la Mama , Depresión , Fatiga , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Fatiga/etiología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/complicaciones , Femenino , Depresión/etiología , Antineoplásicos/efectos adversos , Terapia por Ejercicio/métodos , Ejercicio Físico/fisiología
8.
Mol Cell ; 63(1): 146-55, 2016 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-27292798

RESUMEN

Deubiquitinating enzymes (DUBs) remove ubiquitin (Ub) from Ub-conjugated substrates to regulate the functional outcome of ubiquitylation. Here we report the discovery of a new family of DUBs, which we have named MINDY (motif interacting with Ub-containing novel DUB family). Found in all eukaryotes, MINDY-family DUBs are highly selective at cleaving K48-linked polyUb, a signal that targets proteins for degradation. We identify the catalytic activity to be encoded within a previously unannotated domain, the crystal structure of which reveals a distinct protein fold with no homology to any of the known DUBs. The crystal structure of MINDY-1 (also known as FAM63A) in complex with propargylated Ub reveals conformational changes that realign the active site for catalysis. MINDY-1 prefers cleaving long polyUb chains and works by trimming chains from the distal end. Collectively, our results reveal a new family of DUBs that may have specialized roles in regulating proteostasis.


Asunto(s)
Enzimas Desubicuitinizantes/metabolismo , Evolución Molecular , Poliubiquitina/metabolismo , Secuencia de Aminoácidos , Dominio Catalítico , Secuencia Conservada , Enzimas Desubicuitinizantes/química , Humanos , Proteínas de la Membrana/química , Proteínas de la Membrana/metabolismo , Modelos Moleculares , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Pliegue de Proteína , Relación Estructura-Actividad , Especificidad por Sustrato , Proteínas Supresoras de Tumor/química , Proteínas Supresoras de Tumor/metabolismo , Ubiquitina Tiolesterasa/química , Ubiquitina Tiolesterasa/metabolismo , Ubiquitinación
9.
Neurol Sci ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39269572

RESUMEN

BACKGROUD: Multiple Sclerosis (MS) is a complex and chronic autoimmune disease that affects the central nervous system. Inflammation and demyelination characterize it, which results in a range of neurological impairments. The increasing worldwide occurrence of MS, affecting an estimated 2.8 million individuals in 2020, highlights the urgent requirement for further research to tackle the significant impact it has on individuals and healthcare systems globally. OBJECTIVE: In this study, we wanted to explore the complex function of the endoplasmic reticulum (ER) in the origin, development, and resolution of MS, emphasizing its importance in neuroinflammatory illnesses. The ER has become a central focus in comprehending the pathogenesis of MS. Upon reviewing the literature, we observed a lack of thorough analysis that explores the involvement of endoplasmic reticulum stress in multiple sclerosis. Thus, we aimed through this research to examine the correlations between ER stress and its influence on immunological dysregulation, demyelination, and neurodegeneration in MS. FINDINGS: Based on the latest clinical trials, we suggested theories that explore possible biomarkers linked to ER stress and the unfolded protein response. Identifying molecules that are suggestive of early stages of illness and can serve as prognostic tools for improving our understanding of the heterogeneity of MS and offering novel approaches for managing the disease. Finally, through our comprehensive search, we wanted to offer a plan for future research, suggesting new and creative methods for managing MS and encouraging the creation of specific treatments that aim to reduce the impact of MS on individuals worldwide.

10.
Clin Otolaryngol ; 49(5): 578-587, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38877737

RESUMEN

OBJECTIVES: Tonsillectomy and adenoidectomy are common surgical procedures that cause persistent pain, bleeding, and functional limitations. We aimed to investigate the efficacy of celecoxib compared with a placebo for managing post-tonsillectomy or adenoidectomy pain and other adverse events. DESIGN: Systematic review and meta-analysis. METHODS: We conducted a systematic literature search in the PubMed, Cochrane, and Google Scholar databases from inception until July 2023. Dichotomous outcomes have been reported as risk ratios (RR) while continuous outcomes were reported using mean differences (MD). A funnel plot was drawn to investigate publication bias. RESULTS: From 1394 records identified, 6 randomised double-blind trials comprising 591 participants undergoing tonsillectomy and/or adenoidectomy were eligible for inclusion. A high dose (400 mg) of celecoxib was effective in decreasing the pain score for 'worst pain' after the procedure (MD: -10.98, [95% CI: -11.53, -10.42], p < .01, I2 = 0%) while a low dose (200 mg) was not significantly effective (p = 0.31). For managing other outcomes such as vomiting (RR: 1.37 [95% CI: 0.69, 2.68], p = 0.37, I2 = 67%), diarrhoea (RR: 1.41, [95% CI: 0.75, 2.64], p = .29, I2 = 42%), dizziness/drowsiness (RR: 0.90, [95% CI: 0.71, 1.15], p = .48, I2 = 0%), functional recovery time (p = .74), and headache (p = .91), there was no significant difference between the group on celecoxib and the placebo group regardless of dosage. Finally, there was no significant difference (RR: 1.02, [95% CI: 0.91, 1.15], p = .69, I2 = 0%) in the effect of the intervention on minimum bleeding, moderate bleeding, and profuse bleeding. CONCLUSION: This meta-analysis provides robust evidence pooled from high-quality trials and raises questions about the efficacy of celecoxib for tonsillectomy and/or adenoidectomy, challenging existing perceptions.


Asunto(s)
Adenoidectomía , Celecoxib , Inhibidores de la Ciclooxigenasa 2 , Dolor Postoperatorio , Ensayos Clínicos Controlados Aleatorios como Asunto , Tonsilectomía , Humanos , Celecoxib/uso terapéutico , Celecoxib/administración & dosificación , Dolor Postoperatorio/tratamiento farmacológico , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Inhibidores de la Ciclooxigenasa 2/administración & dosificación
11.
J Pak Med Assoc ; 74(3): 450-455, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38591276

RESUMEN

Objectives: To assess the visual improvement and mean residual astigmatism in patients who underwent cataract surgery with toric intraocular lens. METHODS: The retrospective, observational study was conducted at the Department of Ophthalmology, Aga Khan University Hospital, Karachi, and comprised data from January 1, 2018, to December 31, 2020, related to adult patients who had regular astigmatism of at least 0.75D and underwent cataract surgery with toric intraocular lens implantation using a digital marker. The patients were followed up on post-operative days 1, 7, 30, 90 and 180. Along with age, the degree of astigmatism was noted. The visual acuity was calculated pre- and post-operatively. The mean residual astigmatism was then noted for all patients post-operatively. Data was analysed using SPSS 22. RESULTS: The sample comprised 240 eyes of 177 patients; 99(55.9%) males and 78(44.1%) females. The mean age of the sample was 62.5±10.6 years. The mean unaided visual acuity improved post-operatively from 0.57±0.38 to 0.07±0.22 at 90 days. At the 30-day follow-up, mean residual astigmatism had reduced from 1.52±0.84 to 0.01±0.09 (p<0.001). The mean intraocular lens rotation from the intended axis was 0.73°±0.92° on day 30. CONCLUSIONS: Toric intraocular lens implantation using a digital marker could effectively reduce the post-operative cylinder, and improve the unaided visual acuity following cataract surgery.


Asunto(s)
Astigmatismo , Catarata , Lentes Intraoculares , Facoemulsificación , Masculino , Adulto , Femenino , Humanos , Persona de Mediana Edad , Anciano , Implantación de Lentes Intraoculares , Astigmatismo/cirugía , Estudios Retrospectivos , Catarata/complicaciones , Catarata/terapia , Refracción Ocular
12.
Pak J Med Sci ; 40(2ICON Suppl): S87-S90, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38328640

RESUMEN

Intraabdominal cystic lesions diagnosed during antenatal period are uncommon. They are found to have varying origins, with renal tract being the most common site. Rarely, a large unilateral cystic lesion of renal origin is caused by Pelviureteric junction obstruction, crossing the midline, leading to compression of the contralateral kidney. We present a case of a neonate who was diagnosed with a large abdominal cyst in the antenatal period. The cyst persisted and crossed the midline causing hydronephrosis on the contralateral side. This is an unusual presentation of a commonly occurring condition, usually such large cyst at birth origins from alimentary tract rather renal system. It is important to understand unusual presentations of intraabdominal lesions and the associated pathology. It is mandatory to rule out renal obstruction, if there is any decompression of renal function, it is mandatory to save renal function till the time of definitive surgery.

13.
Pak J Pharm Sci ; 37(1(Special)): 185-189, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38747268

RESUMEN

Burn is a debilitating and devastating emergency with many physical and psychological sequelae. Essential steps in burn wound management include cleansing/wound debridement, application of topical antimicrobial and dressing of affected body areas. Objective of this study is comparison in effectiveness of Hydro-fiber Silver dressing and 1% silver sulfadiazine dressing in management of pediatric burn patients in terms of wound healing. After ethical approval, 264 patients were enrolled and divided into two groups. Patients were managed with hydro-fiber silver dressing in group A and 1% silver sulfadiazine dressing in group B. An experienced pediatric surgeon examined the wounds for re epithelialization and efficacy was labeled after 15 days. Out of 264 enrolled patients 148(56.06%) were males and 116(43.94%) were females. Mean age of patients was 3.73±2.34 years. Type of burn was Scald in 215(81.4%) patients and flame in 49(18.6%). Depth of burn was 2nd degree in 185(70.08%) patients and 3rd degree in 79(29.92%) patients. Mean TBSA was 19.93±9.62%. In group A the efficacy was achieved in 91(68.9%) patients whereas in group B the efficacy was achieved in 73(55.3%) patients (p-value<0.05). Hydro-fiber Silver dressing is significantly more efficacious as compared to 1% silver sulfadiazine dressing for treatment of pediatric burn.


Asunto(s)
Vendajes , Quemaduras , Sulfadiazina de Plata , Humanos , Sulfadiazina de Plata/uso terapéutico , Sulfadiazina de Plata/administración & dosificación , Quemaduras/terapia , Quemaduras/tratamiento farmacológico , Femenino , Masculino , Preescolar , Niño , Cicatrización de Heridas/efectos de los fármacos , Resultado del Tratamiento , Lactante , Antiinfecciosos Locales/uso terapéutico , Antiinfecciosos Locales/administración & dosificación , Plata/uso terapéutico
14.
Semin Cancer Biol ; 86(Pt 2): 310-324, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35787941

RESUMEN

Recently, green nanotechnology got great attention due to their reliable, sustainable, and eco-friendly synthesis protocols. The green nanoparticles (GNPs) are preferred over chemically synthesized nanoparticles owing to less destructive effects associated with the synthesis procedures as well as therapeutic involvement. In this review, we have discussed the applications of GNPs in inflammation-mediated disorders, with special emphasis on cancer, initiated due to oxidative stress and inflammatory cascade. Real-time mechanism based studies on GNPs have suggested their anticancer effects through inducing apoptosis, inhibiting angiogenesis, tissue invasion metastasis, reduced replicative capabilities in addition to target specific different signaling molecules and cascades involved in the development or progression of cancer. Moreover, the association of GNPs with the inhibition or induction of autophagy for the management of cancer has also been discussed. A large number of studies showed the GNPs have multifunctional biomedical properties of theranostic prominence. Therefore, the development of GNPs with naturally established systems could upsurge their definite applications as biomedicines including target specific destruction of the cancerous cells.


Asunto(s)
Nanopartículas del Metal , Neoplasias , Humanos , Oro/química , Oro/farmacología , Nanomedicina , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Neoplasias/tratamiento farmacológico , Apoptosis , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico
15.
Anal Chem ; 95(21): 8189-8196, 2023 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-37196155

RESUMEN

Top-down liquid chromatography-mass spectrometry (LC-MS) analyzes intact proteoforms and generates mass spectra containing peaks of proteoforms with various isotopic compositions, charge states, and retention times. An essential step in top-down MS data analysis is proteoform feature detection, which aims to group these peaks into peak sets (features), each containing all peaks of a proteoform. Accurate protein feature detection enhances the accuracy in MS-based proteoform identification and quantification. Here, we present TopFD, a software tool for top-down MS feature detection that integrates algorithms for proteoform feature detection, feature boundary refinement, and machine learning models for proteoform feature evaluation. We performed extensive benchmarking of TopFD, ProMex, FlashDeconv, and Xtract using seven top-down MS data sets and demonstrated that TopFD outperforms other tools in feature accuracy, reproducibility, and feature abundance reproducibility.


Asunto(s)
Proteoma , Proteómica , Proteómica/métodos , Reproducibilidad de los Resultados , Proteoma/análisis , Espectrometría de Masas , Programas Informáticos
16.
BMC Plant Biol ; 23(1): 41, 2023 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-36653749

RESUMEN

BACKGROUND: Heterosis, or hybrid vigor, refers to the phenotypic superiority of an F1 hybrid relative to its parents in terms of growth rate, biomass production, grain yield, and stress tolerance. Light is an energy source and main environmental cue with marked impacts on heterosis in plants. Research into the production applications and mechanism of heterosis has been conducted for over a century and a half, but little is known about the effect of light on plant heterosis. RESULTS: In this study, an integrated transcriptome and metabolome analysis was performed using maize (Zea mays L.) inbred parents, B73 and Mo17, and their hybrids, B73 × Mo17 (BM) and Mo17 × B73 (MB), grown in darkness or under far-red, red, or blue light. Most differentially expressed genes (73.72-92.50%) and differentially accumulated metabolites (84.74-94.32%) exhibited non-additive effects in BM and MB hybrids. Gene Ontology analysis revealed that differential genes and metabolites were involved in glutathione transfer, carbohydrate transport, terpenoid biosynthesis, and photosynthesis. The darkness, far-red, red, and blue light treatments were all associated with phenylpropanoid-flavonoid biosynthesis by Weighted Gene Co-expression Network Analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Five genes and seven metabolites related to phenylpropanoid-flavonoid biosynthesis pathway were identified as potential contributors to the interactions between maize heterosis and light conditions. Consistent with the strong mid-parent heterosis observed for metabolites, significant increases in both fresh and dry weights were found in the MB and BM hybrids compared with their inbred parents. Unexpectedly, increasing light intensity resulted in higher biomass heterosis in MB, but lower biomass heterosis in BM. CONCLUSIONS: The transcriptomic and metabolomic results provide unique insights into the effects of light quality on gene expression patterns and genotype-environment interactions, and have implications for gene mining of heterotic loci to improve maize production.


Asunto(s)
Transcriptoma , Zea mays , Zea mays/metabolismo , Hibridación Genética , Vigor Híbrido/genética , Perfilación de la Expresión Génica , Metaboloma , Regulación de la Expresión Génica de las Plantas
17.
BMC Plant Biol ; 23(1): 172, 2023 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-37003962

RESUMEN

BACKGROUND: Plant aquaporins are critical genetic players performing multiple biological functions, especially climate resilience and water-use efficiency. Their genomic diversity across genus Oryza is yet to be explored. RESULTS: This study identified 369 aquaporin-encoding genes from 11 cultivated and wild rice species and further categorized these into four major subfamilies, among which small basic intrinsic proteins are speculated to be ancestral to all land plant aquaporins. Evolutionarily conserved motifs in peptides of aquaporins participate in transmembrane transport of materials and their relatively complex gene structures provide an evolutionary playground for regulation of genome structure and transcription. Duplication and evolution analyses revealed higher genetic conservation among Oryza aquaporins and strong purifying selections are assisting in conserving the climate resilience associated functions. Promoter analysis highlighted enrichment of gene upstream regions with cis-acting regulatory elements involved in diverse biological processes, whereas miRNA target site prediction analysis unveiled substantial involvement of osa-miR2102-3p, osa-miR2927 and osa-miR5075 in post-transcriptional regulation of gene expression patterns. Moreover, expression patterns of japonica aquaporins were significantly perturbed in response to different treatment levels of six phytohormones and four abiotic stresses, suggesting their multifarious roles in plants survival under stressed environments. Furthermore, superior haplotypes of seven conserved orthologous aquaporins for higher thousand-grain weight are reported from a gold mine of 3,010 sequenced rice pangenomes. CONCLUSIONS: This study unveils the complete genomic atlas of aquaporins across genus Oryza and provides a comprehensive genetic resource for genomics-assisted development of climate-resilient rice cultivars.


Asunto(s)
Acuaporinas , Oryza , Oryza/metabolismo , Genómica , Estrés Fisiológico/genética , Regiones Promotoras Genéticas , Acuaporinas/genética , Acuaporinas/metabolismo , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Filogenia
18.
BMC Plant Biol ; 23(1): 256, 2023 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-37189032

RESUMEN

BACKGROUND: Heat stress threatens rice yield and quality at flowering stage. In this study, average relative seed setting rate under heat stress (RHSR) and genotypes of 284 varieties were used for a genome-wide association study. RESULTS: We identified eight and six QTLs distributed on chromosomes 1, 3, 4, 5, 7 and 12 in the full population and indica, respectively. qHTT4.2 was detected in both the full population and indica as an overlapping QTL. RHSR was positively correlated with the accumulation of heat-tolerant superior alleles (SA), and indica accession contained at least two heat-tolerant SA with average RHSR greater than 43%, meeting the needs of stable production and heat-tolerant QTLs were offer yield basic for chalkiness degree, amylose content, gel consistency and gelatinization temperature. Chalkiness degree, amylose content, and gelatinization temperature under heat stress increased with accumulation of heat-tolerant SA. Gel consistency under heat stress decreased with polymerization of heat-tolerant SA. The study revealed qHTT4.2 as a stable heat-tolerant QTL that can be used for breeding that was detected in the full population and indica. And the grain quality of qHTT4.2-haplotype1 (Hap1) with chalk5, wx, and alk was better than that of qHTT4.2-Hap1 with CHALK5, WX, and ALK. Twelve putative candidate genes were identified for qHTT4.2 that enhance RHSR based on gene expression data and these genes were validated in two groups. Candidate genes LOC_Os04g52830 and LOC_Os04g52870 were induced by high temperature. CONCLUSIONS: Our findings identify strong heat-tolerant cultivars and heat-tolerant QTLs with great potential value to improve rice tolerance to heat stress, and suggest a strategy for the breeding of yield-balance-quality heat-tolerant crop varieties.


Asunto(s)
Oryza , Oryza/genética , Oryza/metabolismo , Estudio de Asociación del Genoma Completo , Alelos , Amilosa/metabolismo , Fitomejoramiento , Proteínas Tirosina Quinasas Receptoras/genética
19.
Small ; 19(47): e2303787, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37438654

RESUMEN

Using three-dimensional current collectors (3DCC) as frameworks for lithium metal anodes (LMAs) is a promising approach to inhibit dendrite growth. However, the intrinsically accumulated current density on the top surface and limited Li-ion transfer in the interior of 3DCC still lead to the formation of lithium dendrites, which can pose safety risks. In this study, it reports that gradient lithiophilic structures can induce uniform lithium deposition within the interior of the 3DCC, greatly suppressing dendrite formation, as confirmed by COMSOL simulations and experimental results. With this concept, a gradient-structured zinc oxide-loaded copper foam (GSZO-CF) is synthesized via an easy solution-combustion method at low cost. The resulting Li@GSZO-CF symmetric cells demonstrate stable cycling performance for over 800 cycles, with an ultra-deep capacity of 10 mAh cm-2 even under an ultra-high current density of 50 mA cm-2 , the top results reported in the literature. Moreover, when combined with a LiFePO4 (LFP) cathode under a low negative/positive (N/P) capacity ratio of 2.9, the Li@GSZO-CF||LFP full cells exhibit stable performance for 200 cycles, with a discharge capacity of 130 mAh g-1 and retention of 85.5% at a charging/discharging rate of 1C. These findings suggest a promising strategy for the development of new-generation LMAs.

20.
Small ; 19(44): e2304686, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37715055

RESUMEN

The fabrication of low-cost, effective, and highly integrated nanostructured materials through simple and reproducible methods for high-energy-density supercapacitors is highly desirable. Herein, an activated carbon cloth (ACC) is designed as the functional scaffold for supercapacitors and treated hydrothermally to deposit NiCo nanoneedles working as internal core, followed by a dip-dry coating of NiOOH nanoflakes core-shell and uniform hydrothermal deposition of CoMoO4 nanosheets serving as an external shell. The structured core-shell heterostructure ACC@NiCo@NiOOH@CoMoO4 electrode resulted in exceptional specific areal capacitance of 2920 mF cm-2 and exceptional cycling stability for 10 000 cycles. Moreover, the fabricated electrode is developed into an asymmetric supercapacitor which demonstrates excellent areal capacitance, energy density, and power density within the broad potential window of 1.7 V with a cycling life of 92.4% after 10 000 charge-discharge cycles, which reflects excellent cycle life. The distinctive core-shell structure, highly conductive substrate, and synergetic effect of coated material results in more electrochemical active sites and flanges for effective electrons and ion transportation. This unique technique provides a new perspective for cost-efficient supercapacitor applications.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA