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1.
Chem Rec ; 24(1): e202300226, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37728184

RESUMEN

In the recent times research towards solid state supercapacitors (SSS) have increased drastically due to the promising performance in futuristic technologies particularly in portable and flexible electronics like smart watches, smart fabrics, foldable smartphones and tablets. Also, when compared to supercapacitors using liquid electrolyte, solid electrolyte has several advantages like high energy density, safety, high cycle life, flexible form factor, and less environmental impact. The crucial factor determining the sustainability of a technology is the eco-friendliness since the natural resources are being exploited in a wide scale. Numerous studies have focused on biodegradable materials for supercapacitor electrodes, electrolytes, and other inactive components. Making use of these biodegradable materials to design a SSS enables the technology to sustain for a very long time since biodegradable materials are not only environment friendly but also, they show relatively high performance. This review focuses on recent progress of different biodegradable electrodes, and electrolytes along with their properties, electrochemical performance and biodegradable capabilities for SSS have been analyzed and provides a concise summary enabling readers to understand the importance of biodegradable materials and to narrow down the research in a more rational way.

2.
Niger J Clin Pract ; 26(11): 1703-1708, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-38044776

RESUMEN

BACKGROUND: The oral cavity has been referred to as "the gateway to overall health." It is also said to be the meeting point of medicine and dentistry. AIMS: Our study sought to determine the extent to which the public was aware of the connection between oral/periodontal conditions and general health. SETTINGS AND DESIGN: The observational cross-sectional study's questionnaire was sectioned into oral health awareness, systemic influence on oral health, and personal oral health assessment. MATERIALS AND METHODS: A total of 994 responses were recorded and a Chi-square test was performed to uncover the relationships using SPSS version 22.0. According to responses, 70% of the population on average comprehended the responses to the majority of the oral health awareness-related questions. RESULTS: It has been noticed that only 30% of the general public was aware of the prevalent health issues like diabetes, hypertension, and malnutrition's impact on dental health. However, more than 60% had confidence in their oral health and gave a rating of at least 5. CONCLUSION: The study indicates that a good number of the population was prioritizing their oral health. However, there exists a definitive need to improve oral health awareness thereby ameliorating the overall health of an individual.


Asunto(s)
Diabetes Mellitus , Medicina , Enfermedades Periodontales , Humanos , Estudios Transversales , India/epidemiología
3.
Niger J Clin Pract ; 26(9): 1215-1225, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37794532

RESUMEN

Dental implants are considered an ideal treatment for a missing single tooth. Immediate loading of implants can hasten the procedure, providing comfort to the patients. Recently, immediate loading of implants has gained much importance as it helps hasten the procedure and provides more comfort to patients. A previous systematic review published 5 years ago compared the success rates between immediate and conventional loading. There are several factors that influence the success rate of implants that were not discussed in detail in the previous review. Hence, the present systematic review is done to report differences in the outcomes from single implant restorations of missing teeth in the posterior region in patients who were subjected to immediate loading and conventional loading. A follow up for 1 year was done. Electronic databases of Medline, Scopus, and Web of Science were searched for publications in the English Language during May 2021. The search results yielded 306 articles, out of which 225 were excluded based on title and abstract screening. Screening of the remaining 81 full text articles yielded 14 original research articles that satisfied the predefined inclusion criteria. Meta analysis was not possible due to the heterogeneity of the data. The overall success rate of the immediate loading of a single implant is 94.31%. Implants in the maxillary region had a higher survival rate than those in the mandibular region. The age range between 18 and 80 years showed good prognosis and outcomes in older individuals. Good oral hygiene was emphasized for all patients to prevent any secondary conditions or delays in healing.


Asunto(s)
Anodoncia , Implantes Dentales , Carga Inmediata del Implante Dental , Pérdida de Diente , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Adulto Joven , Prótesis Dental de Soporte Implantado , Carga Inmediata del Implante Dental/métodos , Pérdida de Diente/cirugía
4.
Funct Integr Genomics ; 22(6): 1345-1360, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35987846

RESUMEN

Deregulated transcription programs and signaling pathways are the critical factors involved in the process of carcinogenesis. Signaling pathway-based classification of tumors is expected to pave the way for the development of targeted therapeutics. We investigated the OCT4-mediated transcription program in the gene expression profiles of 939 gastric tumor samples. A set of 84 genes showing positive correlation with the activation pattern of the available OCT4 gene sets were found to consistently express in diffuse, poorly differentiated, and stage-III gastric tumors with poor prognosis. We also developed stable OCT4-silenced gastric cancer cells and the resultant gene expression changes were investigated by genome-wide mRNA profiling. Functional genomic investigation of the genes downregulated in OCT4-silenced cells and the pathways co-activated with OCT4 gene set across gastric tumors revealed the positive association of dysregulated OCT4 with TGF-ß, GLI, PRC2/EzH2, Wnt, KRAS, STK33, and YAP signaling pathways in diffuse subtype gastric tumors. Elevated expression of OCT4 gene set was identified to represent the previously described EMT_UP as well as the GENOMICALLY STABLE subtypes of gastric tumors. Integrative genomic screening of the drug sensitivity of gastric cancer cells in correlation with the expression of OCT4 gene set across drug sensitivity databases revealed the inhibitors of tyrosine kinases, HDAC, and HSP90 to have a negative correlation and needs to be investigated for their potential therapeutic features for the subset of OCT4-activated gastric tumors. Thus, the subset of gastric tumors with OCT4 activation, the associated oncogenic signaling pathways, and potential therapeutic candidates were identified for the development of targeted therapeutic strategies.


Asunto(s)
Factor 3 de Transcripción de Unión a Octámeros , Neoplasias Gástricas , Humanos , Carcinogénesis/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Transducción de Señal , Neoplasias Gástricas/metabolismo , Factor de Crecimiento Transformador beta/genética , Factor 3 de Transcripción de Unión a Octámeros/genética
5.
Dev Cell ; 57(5): 654-669.e9, 2022 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-35247316

RESUMEN

The response to oxygen availability is a fundamental process concerning metabolism and survival/death in all mitochondria-containing eukaryotes. However, the known oxygen-sensing mechanism in mammalian cells depends on pVHL, which is only found among metazoans but not in other species. Here, we present an alternative oxygen-sensing pathway regulated by ATE1, an enzyme ubiquitously conserved in eukaryotes that influences protein degradation by posttranslational arginylation. We report that ATE1 centrally controls the hypoxic response and glycolysis in mammalian cells by preferentially arginylating HIF1α that is hydroxylated by PHD in the presence of oxygen. Furthermore, the degradation of arginylated HIF1α is independent of pVHL E3 ubiquitin ligase but dependent on the UBR family proteins. Bioinformatic analysis of human tumor data reveals that the ATE1/UBR and pVHL pathways jointly regulate oxygen sensing in a transcription-independent manner with different tissue specificities. Phylogenetic analysis suggests that eukaryotic ATE1 likely evolved during mitochondrial domestication, much earlier than pVHL.


Asunto(s)
Aminoaciltransferasas , Oxígeno , Aminoaciltransferasas/genética , Aminoaciltransferasas/metabolismo , Animales , Humanos , Mamíferos/metabolismo , Filogenia , Proteolisis
7.
Mater Today Proc ; 46: 9697-9701, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33014714

RESUMEN

In today's industrial scenarios, having continuous improvement to increase the process efficiency is one of the key measures. Especially manufacturing and automotive industries are putting forth a lot of resource and time to improve the efficiency of the process without compromising the current production capacity and improve the quality rate. This paper deals with a case study of retrofitting a two-way chuck in a vertical lathe machine and thereby calculating the overall equipment effectiveness of the entire automated process in piston manufacturing. The current automated production line of piston manufacturing is being analysed with the help of value stream mapping (VSM). Value stream mapping is widely used by the industrial persons to identify the wastes i.e., non-value-added time in the process line. The Critical to Quality (CTQ) parameters in an efficient production line such as lead time, value added time, transfer time and takt time have taken into account for identifying the places of improvement. A new retrofitted design has been suggested which can increase the production efficiency of the current system with effective utilization of available resources. After implementing the modified retrofit design, the subsequent changes in the process line have also been stated through Future state VSM, which clearly indicates the reduction in drop to drop time between the cells which has been considered as the non value added time in the current system. Studies like these shows that effective utilisation of available resources through retrofitting can greatly assist the manufacturers to reduce their cost of additional investment and be sustainable among the growing competitors in the market.

8.
Dalton Trans ; 49(41): 14680-14689, 2020 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-33064113

RESUMEN

A rhodamine appended Fe(iii)-catecholate complex Fe(RhoCat)3 is reported as a smart dual-modal T1 MRI-optical imaging probe. The high spin Fe(iii) coordination sphere and rhodamine unit act as MRI and optical reporters, respectively. The probe showed a r1-relaxivity of 4.37 mM-1 s-1 at 1.41 T via the interaction of second sphere water molecules to coordinated oxygen atoms. It produced an enhanced signal intensity of phantom images on the 7.0 T animal research MRI/MRS scanner at 25 °C and pH 7.3. The interaction of the probe with bovine serum albumin (BSA) significantly improved r1 relaxivity (7.09 mM-1 s-1). Moreover, the optical imaging reporter rhodamine moiety exhibited sensitivity towards biomolecule nitric oxide (NO) and acidic pH via the formation of a ring-opened tautomer of rhodamine, wherein the r1 relaxivity of the probe was enhanced to 5.19 mM-1 s-1 for NO and slightly decreased for acidic pH. Further, the probe visualized NO in adenocarcinoma gastric (AGS) cells via a turn-on fluorescence mechanism with 80% cell viability. Thus, Fe(RhoCat)3 is demonstrated as a potential dual "MRI-ON and Fluorescence-ON" molecular imaging probe to visualize the NO molecule and acidic pH in the tumour microenvironment.


Asunto(s)
Complejos de Coordinación/química , Hierro/química , Imagen por Resonancia Magnética/métodos , Imagen Óptica/métodos , Rodaminas/química , Catecoles/química , Línea Celular Tumoral , Complejos de Coordinación/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Óxido Nítrico/química , Albúmina Sérica Bovina/metabolismo , Tomografía de Coherencia Óptica
9.
Saudi J Anaesth ; 14(3): 397-399, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32934638

RESUMEN

The altered pediatric airway is a nightmare for an anesthesiologist. Managing such cases with limited resources makes it more challenging. Here, we report a case of pediatric patient with altered airway anatomy posted for gastrotomy and feeding tube insertion. This case highlights the management of pediatric difficult airway and discusses the various choices of anesthesia technique.

10.
Spectrochim Acta A Mol Biomol Spectrosc ; 243: 118814, 2020 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-32861203

RESUMEN

An easy and selective method has been developed for the extractive spectrophotometric determination of ruthenium(III) with 4-(4'-flurobenzylideneimino)-3-methyl-5-mercapto-1,2,4-triazole (FBIMMT) as a chelating reagent. The basis of the method is the formation of stable complex of 'soft base' FBIMMT with 'soft acid' ruthenium(III). The reagent FBIMMT in n-butanol easily forms extractable yellow coloured complex with ruthenium(III) in acetate buffer of pH 4.8. The absorbance of [Ru(III)-FBIMMT] complex is measured at 394 nm against the reagent blank. Good linearity range of concentration up to 27.0 µg mL-1 of ruthenium(III) is attained with correlation coefficient R2 = 0.998. The optimum concentration range is 6 to 27.0 µg mL-1 which is deduced by Ringbom's plot. The apparent molar absorptivity found to be 2.75 × 103 L mol-1 cm-1. Some additional characteristics such as limit of detection (LOD = 0.48 µg mL-1), limit of quantification (LOQ = 1.19 µg mL-1), and Sandell's sensitivity (SS = of 0.0367 µg cm-2) are also estimated. The composition of [Ru(III)-FBIMMT] complex has been established from Job's continuous variation method, mole ratio method, and log-log plot method. The specificity towards ruthenium(III) is well studied and appropriate masking agents are applied wherever required to boost it. The intra-day and inter-day precision values are found to be brilliant with % relative standard deviation of 0.52 and 0.68 respectively with % accuracy within the range of 99.00-100. The method is effectively used for determination of ruthenium(III) from water samples, binary and ternary synthetic mixtures, fissium alloy samples and catalyst materials. A scheme for sequential group separation of ruthenium(III), palladium(II) and osmium(VIII) has also been developed. The reproducible results of the present method confirm that the method has a good potential for quantitative determination of ruthenium(III) from various matrices.

11.
Ann N Y Acad Sci ; 1467(1): 94-111, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31944316

RESUMEN

The identification of new drugs for the targeted therapy of gastric cancer remains an important need. The RAS/RAF/MEK/ERK/ELK1 signaling cascade is activated in many cancers, including gastric cancer. To identify the targetable inhibitors of the ERK/MAPK pathway, we performed a repurposing screening of a panel of antimicrobial agents in gastric cancer cells using an ERK/MAPK-driven firefly luciferase reporter assay. Multiple antibiotics were identified to inhibit ERK-mediated transcriptional activity. Among them, doxycycline showed high inhibition of ERK/MAPK-regulated transcriptional activity and the levels of ERK proteins. Doxycycline was further identified to inhibit the proliferation and the colony- and spheroid-forming potential of gastric cancer cells. By in vitro signaling pathway and genome-wide expression profiling analyses, doxycycline was identified to inhibit signaling pathways and transcriptional activities regulated by ER, Myc, E2F1, Wnt, SMAD2/3/4, Notch, and OCT4. Doxycycline was also found to activate p53-, ATF6-, NRF1/2-, and MTF1-mediated transcription and inhibit the transcription of histones, proteasomal genes, fibroblast growth factor, and other oncogenic factors. These observations show the multitargeting and targeted therapeutic features of doxycycline for a subset of gastric tumors.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antibacterianos/farmacología , Proliferación Celular/efectos de los fármacos , Doxiciclina/farmacología , Transducción de Señal/efectos de los fármacos , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/metabolismo , Antibacterianos/uso terapéutico , Doxiciclina/uso terapéutico , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Neoplasias Gástricas/metabolismo
12.
Bio Protoc ; 10(10): e3622, 2020 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-33659295

RESUMEN

In the last decade, genome editing has been the center of attention as a novel tool for mechanistic investigations and for potential clinical applications. Various genome editing tools like meganucleases, zinc finger nucleases (ZFNs), transcription activator-like effector-based nucleases (TALEN), and the clustered regularly interspaced short palindromic repeats (CRISPR)-associated genes (Cas), have been developed in recent years. For the optimal use as well as continued developments of these genome editing tools, the evaluation of their efficiencies and accuracies is vital. Here, we present a protocol for a reporter based on frameshift fluorescence protein which we recently developed to evaluate the efficiency and accuracy of genome editing tools. In this method, a ~20 bp target sequence containing frame-shifting is inserted after the start codon of a cerulean fluorescence protein (CFP) to inactivate its fluorescence, and only a new insertion/deletion event in the target sequence will reactivate the CFP fluorescence. To increase the traceability, an internal ribosome entry site and a red fluorescence protein, mCherryFP, are placed downstream of the reporter. The percentage of CFP-positive cells resulted from in/del mediated fluorescence restoration can be quantified by fluorescence measuring devices as the readout for genome editing frequency. As a demonstration, we present the usage for CRISPR-Cas9 technique here with flow cytometer as the readout for fluorescence changes.

13.
Front Cell Dev Biol ; 8: 603688, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33409279

RESUMEN

Arginyltransferase 1 (ATE1) is an evolutionary-conserved eukaryotic protein that localizes to the cytosol and nucleus. It is the only known enzyme in metazoans and fungi that catalyzes posttranslational arginylation. Lack of arginylation has been linked to an array of human disorders, including cancer, by altering the response to stress and the regulation of metabolism and apoptosis. Although mitochondria play relevant roles in these processes in health and disease, a causal relationship between ATE1 activity and mitochondrial biology has yet to be established. Here, we report a phylogenetic analysis that traces the roots of ATE1 to alpha-proteobacteria, the mitochondrion microbial ancestor. We then demonstrate that a small fraction of ATE1 localizes within mitochondria. Furthermore, the absence of ATE1 influences the levels, organization, and function of respiratory chain complexes in mouse cells. Specifically, ATE1-KO mouse embryonic fibroblasts have increased levels of respiratory supercomplexes I+III2+IVn. However, they have decreased mitochondrial respiration owing to severely lowered complex II levels, which leads to accumulation of succinate and downstream metabolic effects. Taken together, our findings establish a novel pathway for mitochondrial function regulation that might explain ATE1-dependent effects in various disease conditions, including cancer and aging, in which metabolic shifts are part of the pathogenic or deleterious underlying mechanism.

14.
Ann Maxillofac Surg ; 10(2): 287-291, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33708569

RESUMEN

INTRODUCTION: Erich arch bar used for maxillomandibular fixation (MMF) since decades has several disadvantages such as risks of injury, additional operating room time, and gingival trauma. To overcome these downsides, modified Erich arch bar was introduced; however, there is not much available literature, indicating the efficacy of modified Erich arch bar over that of conventional arch bar wire. Therefore, the present study focuses on comparing efficiency of modified arch bar with conventional arch bar. MATERIALS AND METHODS: This comparative randomized study was conducted on 32 patients that required MMF and were divided into Group A patients who received intermaxillary fixation (IMF) with modified Erich arch bars and Group B patients with conventional Erich arch bars. The parameters recorded were average surgical time required, wire prick injuries, IMF stability, occlusal stability, screw loosening, oral hygiene status, and vitality response of the teeth. The variables were statistically analyzed using Student's t-test and Wilcoxon signed-rank test. RESULTS: The wire prick injury, intraoperative time noted in Group A was significantly reduced in comparison to Group B (P < 0.0001). Debris indices were significantly good in Group A in comparison to Group B (P < 0.0001). Nonvitality response of tooth was significantly more in Group B than in Group A patients (P < 0.05). DISCUSSION: The efficiency of modified Erich arch bar group was superior to the conventional arch bar with very limited restrictions.

15.
BMC Genomics ; 20(1): 609, 2019 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-31340764

RESUMEN

BACKGROUND: Reporter methods to quantitatively measure the efficiency and specificity of genome editing tools are important for the development of novel editing techniques and successful applications of available ones. However, the existing methods have major limitations in sensitivity, accuracy, and/or readiness for in vivo applications. Here, we aim to develop a straight-forward method by using nucleotide insertion/deletion resulted from genome editing. In this system, a target sequence with frame-shifting length is inserted after the start codon of a cerulean fluorescence protein (CFP) to inactivate its fluorescence. As such, only a new insertion/deletion event in the target sequence will reactivate the fluorescence. This reporter is therefore termed as "Insertion/deletion-activated frame-shift fluorescence protein". To increase its traceability, an internal ribosome entry site and a red fluorescence protein mCherryFP are placed downstream of the reporter. The percentage of CFP-positive cells can be quantified by fluorescence measuring devices such as flow cytometer as the readout for genome editing frequency. RESULTS: To test the background noise level, sensitivity, and quantitative capacity of this new reporter, we applied this approach to examine the efficiency of genome editing of CRISPR/Cas9 on two different targeting sequences and in three different cell lines, in the presence or absence of guide-RNAs with or without efficiency-compromising mutations. We found that the insertion/deletion-activated frame-shift fluorescence protein has very low background signal, can detect low-efficiency genome editing events driven by mutated guideRNAs, and can quantitatively distinguish genome editing by normal or mutated guideRNA. To further test whether the positive editing event detected by this reporter indeed correspond to genuine insertion/deletion on the genome, we enriched the CFP-positive cells to examine their fluorescence under confocal microscope and to analyze the DNA sequence of the reporter in the genome by Sanger sequencing. We found that the positive events captured by this reporter indeed correlates with genuine DNA insertion/deletion in the expected genome location. CONCLUSION: The insertion/deletion-activated frame-shift fluorescence protein reporter has very low background, high sensitivity, and is quantitative in nature. It will be able to facilitate the development of new genome editing tools as well as the application of existing tools.


Asunto(s)
Mutación del Sistema de Lectura , Edición Génica , Mutación INDEL , Proteínas Luminiscentes/genética , Animales , Células CHO , Sistemas CRISPR-Cas , Codón Iniciador , Cricetulus , Fibroblastos , Fluorescencia , Genes Reporteros , Células HEK293 , Humanos , Sitios Internos de Entrada al Ribosoma , Ratones , ARN Guía de Kinetoplastida
17.
J Maxillofac Oral Surg ; 18(1): 15-22, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30728686

RESUMEN

INTRODUCTION: Of the many chronic painful conditions, trigeminal neuralgia (TN) affecting the orofacial region needs the particular attention of physicians and surgeons, especially those specialising in the maxillofacial region. Treatment protocols for the management of classic TN include pharmacology and surgical intervention. Oral and maxillofacial surgeons have traditionally employed the peripheral neurectomy in the surgical management of TN. This review aims to evaluate the efficacy of peripheral neurectomy in the management of TN with regard to (a) the relief of symptoms in comparison with standard neurosurgical procedures and (b) the duration of pain relief and complications observed compared to standard neurosurgical procedures. METHODS: The review of the literature was done according to PRISMA guidelines and included randomised controlled trials, reviews and prospective clinical studies involving surgical procedures for the management of TN. The primary outcomes evaluated were (a) initial relief of pain, (b) duration of relief of pain, (c) complications observed with ablative procedures and (d) recurrence of symptoms. A total of 43 studies fulfilled the inclusion criteria. RESULTS: In a total of 7913 patients from the 43 studies, central procedures were found to have best results for both quality and duration of pain relief. Percutaneous and peripheral procedures were associated with increased recurrence rates. The consolidated rates of complication for peripheral, percutaneous and central procedures were 39.46, 65.42 and 10.41%, respectively. The use of peripheral neurectomy alone in the management of classic TN was observed in 10 studies. CONCLUSION: Peripheral neurectomy in TN is associated with lesser quality of pain relief in comparison with central neurosurgical procedures. It also provides only short- to medium-term pain relief. Most studies with the use of peripheral neurectomy involved only a small group of patients with short follow-up periods. Oral and maxillofacial surgeons must not consider the peripheral neurectomy as the first surgical option in the management of classic TN. Long-term results can be achieved better with appropriate central neurosurgical procedures and pharmacotherapy.

18.
G3 (Bethesda) ; 9(3): 867-877, 2019 03 07.
Artículo en Inglés | MEDLINE | ID: mdl-30679249

RESUMEN

Clathrin is a major coat protein involved in vesicle formation during endocytosis and transport in the endosomal/trans Golgi system. Clathrin is required for normal growth of yeast (Saccharomyces cerevisiae) and in some genetic backgrounds deletion of the clathrin heavy chain gene (CHC1) is lethal. Our lab defined a locus referred to as " s uppressor of c lathrin d eficiency" (SCD1). In the presence of the scd1-v allele ("v" - viable), yeast cells lacking clathrin heavy chain survive but grow slowly, are morphologically abnormal and have many membrane trafficking defects. In the presence of scd1-i ("i"- inviable), chc1∆ causes lethality. As a strategy to identify SCD1, we used pooled linkage analysis and whole genome sequencing. Here, we report that PAL2 (YHR097C) is the SCD1 locus. pal2∆ is synthetic lethal with chc1∆; whereas a deletion of its paralog, PAL1, is not synthetic lethal with clathrin deficiency. Like Pal1, Pal2 has two NPF motifs that are potential binding sites for EH domain proteins such as the early endocytic factor Ede1, and Pal2 associates with Ede1 Also, GFP-tagged Pal2p localizes to cortical patches containing other immobile phase endocytic coat factors. Overall, our data show that PAL2 is the SCD1 locus and the Pal2 protein has characteristics of an early factor involved in clathrin-mediated endocytosis.


Asunto(s)
Clatrina , Endocitosis , Sitios Genéticos , Receptores de Superficie Celular/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Receptores de Superficie Celular/genética , Saccharomyces cerevisiae/fisiología , Proteínas de Saccharomyces cerevisiae/genética , Secuenciación Completa del Genoma
19.
Oncogene ; 38(6): 838-851, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30177837

RESUMEN

Most prostate cancer cases remain indolent for long periods of time, but metastatic progression quickly worsens the prognosis and leads to mortality. However, little is known about what promotes the metastasis of prostate cancer and there is a lack of effective prognostic indicators, making it immensely difficult to manage options for treatment or surveillance. Arginyltransferase 1 (Ate1) is the enzyme mediating post-translational protein arginylation, which has recently been identified as a master regulator affecting many cancer-relevant pathways including stress response, cell cycle checkpoints, and cell migration/adhesion. However, the precise role of Ate1 in cancer remains unknown. In this study, we found the occurrence of metastasis of prostate cancer is inversely correlated with the levels of Ate1 protein and mRNA in the primary tumor. We also found that metastatic prostate cancer cell lines have a reduced level of Ate1 protein compared to non-metastatic cell lines, and that a depletion of Ate1 drives prostate cancer cells towards more aggressive pro-metastatic phenotypes without affecting proliferation rates. Furthermore, we demonstrated that a reduction of Ate1 can result from chronic stress, and that shRNA-reduced Ate1 increases cellular resistance to stress, and drives spontaneous and stress-induced genomic mutations. Finally, by using a prostate orthotropic xenograft mouse model, we found that a reduction of Ate1 was sufficient to enhance the metastatic phenotypes of prostate cancer cell line PC-3 in vivo. Our study revealed a novel role of Ate1 in suppressing prostate cancer metastasis, which has a profound significance for establishing metastatic indicators for prostate cancer, and for finding potential treatments to prevent its metastasis.


Asunto(s)
Aminoaciltransferasas/metabolismo , Movimiento Celular , Proteínas de Neoplasias/metabolismo , Neoplasias de la Próstata/enzimología , Neoplasias de la Próstata/metabolismo , Aminoaciltransferasas/genética , Animales , Células HEK293 , Humanos , Masculino , Ratones , Ratones Noqueados , Metástasis de la Neoplasia , Proteínas de Neoplasias/genética , Pronóstico , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología
20.
FEBS Lett ; 592(11): 1870-1881, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29772604

RESUMEN

Localization of mRNAs depends on specific RNA-binding proteins (RBPs) and critically contributes not only to cell polarization but also to basal cell function. The yeast RBP Khd1p binds to several hundred mRNAs, the majority of which encodes secreted or membrane proteins. We demonstrate that a subfraction of Khd1p associates with artificial liposomes and endoplasmic reticulum (ER), and that Khd1p endomembrane association is partially dependent on its binding to RNA. ER targeting of at least two mRNAs, MID2 and SLG1/WSC1, requires KHD1 but is independent of their translation. Together, our results suggest interdependence of Khd1p and mRNA for their targeting to the ER and presents additional evidence for signal sequence-independent, RBP-mediated mRNA targeting.


Asunto(s)
Retículo Endoplásmico/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Glicoproteínas de Membrana/metabolismo , ARN de Hongos/metabolismo , ARN Mensajero/metabolismo , Ribonucleoproteínas/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Retículo Endoplásmico/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Glicoproteínas de Membrana/genética , ARN de Hongos/genética , ARN Mensajero/genética , Ribonucleoproteínas/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética
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