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1.
Cureus ; 16(3): e55908, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38601391

RESUMO

Introduction Physical therapy (PT) is an effective nonoperative treatment for various orthopedic diagnoses. However, patients may have many reasons to dismiss PT, including favoring another intervention for their injury, time constraints, transportation, and cost. This dismissal of PT may contribute to inadequate patient compliance. This study aimed to elucidate patient compliance with a basic PT prescription and whether PT led to subjective injury improvement. Methods This is a retrospective study of patients observed in Stony Brook Orthopedic clinics from 08/01/2022 to 12/23/2022. Patients prescribed PT received a phone call six weeks after the PT prescription. The primary outcome was patient attendance at PT. Secondary outcomes were subjective; symptomatic improvement was listed as better, worse, or the same. Chi-square testing was used to compare outcomes. Results A total of 100 patients were enrolled in the study. Patients prescribed PT following surgery were more likely to attend compared to patients prescribed PT as a primary treatment (P value=0.027). The association between attendance at PT and a change in subjective symptoms (better, worse, same) was not significant. Patients' age, sex, and chronicity of injury were not significant factors in PT attendance. Of the 40 patients who did not attend PT, 14 cited time constraints, 11 utilized self-directed treatment, three cited insurance, two cited transportation, and 10 cited other reasons. Conclusions Overall, postoperative patients were more likely to attend PT compared to patients prescribed PT as a primary treatment. Factors such as age, sex, and chronicity of injury did not affect whether a patient attended PT. Of the patients enrolled, 71% stated subjective improvement in symptoms, but there was no association between symptoms and PT attendance. This study highlights the characteristics of those patient factors that may influence PT compliance and underscores the importance of further research into the population most likely to attend and benefit from PT.

2.
Biol Rev Camb Philos Soc ; 99(4): 1425-1443, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38509722

RESUMO

Carrion ecology, i.e. the decomposition and recycling of dead animals, has traditionally been neglected as a key process in ecosystem functioning. Similarly, despite the large threats that inland aquatic ecosystems (hereafter, aquatic ecosystems) face, the scientific literature is still largely biased towards terrestrial ecosystems. However, there has been an increasing number of studies on carrion ecology in aquatic ecosystems in the last two decades, highlighting their key role in nutrient recirculation and disease control. Thus, a global assessment of the ecological role of scavengers and carrion in aquatic ecosystems is timely. Here, we systematically reviewed scientific articles on carrion ecology in aquatic ecosystems to describe current knowledge, identify research gaps, and promote future studies that will deepen our understanding in this field. We found 206 relevant studies, which were highly biased towards North America, especially in lotic ecosystems, covering short time periods, and overlooking seasonality, a crucial factor in scavenging dynamics. Despite the low number of studies on scavenger assemblages, we recorded 55 orders of invertebrates from 179 families, with Diptera and Coleoptera being the most frequent orders. For vertebrates, we recorded 114 species from 40 families, with birds and mammals being the most common. Our results emphasise the significance of scavengers in stabilising food webs and facilitating nutrient cycling within aquatic ecosystems. Studies were strongly biased towards the assessment of the ecosystem effects of carrion, particularly of salmon carcasses in North America. The second most common research topic was the foraging ecology of vertebrates, which was mostly evaluated through sporadic observations of carrion in the diet. Articles assessing scavenger assemblages were scarce, and only a limited number of these studies evaluated carrion consumption patterns, which serve as a proxy for the role of scavengers in the ecosystem. The ecological functions performed by carrion and scavengers in aquatic ecosystems were diverse. The main ecological functions were carrion as food source and the role of scavengers in nutrient cycling, which appeared in 52.4% (N = 108) and 46.1% (N = 95) of publications, respectively. Ecosystem threats associated with carrion ecology were also identified, the most common being water eutrophication and carrion as source of pathogens (2.4%; N = 5 each). Regarding the effects of carrion on ecosystems, we found studies spanning all ecosystem components (N = 85), from soil or the water column to terrestrial vertebrates, with a particular focus on aquatic invertebrates and fish. Most of these articles found positive effects of carrion on ecosystems (e.g. higher species richness, abundance or fitness; 84.7%; N = 72), while a minority found negative effects, changes in community composition, or even no effects. Enhancing our understanding of scavengers and carrion in aquatic ecosystems is crucial to assessing their current and future roles amidst global change, mainly for water-land nutrient transport, due to changes in the amount and speed of nutrient movement, and for disease control and impact mitigation, due to the predicted increase in occurrence and magnitude of mortality events in aquatic ecosystems.


Assuntos
Ecossistema , Animais , Invertebrados/fisiologia , Cadeia Alimentar , Comportamento Alimentar
3.
Artigo em Inglês | MEDLINE | ID: mdl-38323932

RESUMO

BACKGROUND: Talus bipartitus is a rare skeletal anomaly that may be mistaken for an os trigonum, a relatively common accessory ossicle found posterior to the talus. Both are believed to be formed similarly with the failed fusion of the talus with a second ossification center. Os trigonum is often diagnosed incidentally or found on radiographs obtained in symptomatic patients with signs of os trigonum syndrome, which presents with posterolateral ankle pain. A bipartite talus may also present with similar symptoms but may be differentiated through its articular involvement. CASE: In this article, we describe the rare presentation of tarsal tunnel syndrome in a patient caused by a bipartite talus. The patient underwent surgical decompression with the removal of the posterior fragment. CONCLUSION: A bipartite talus is a rare entity that may be mistaken for an os trigonum, a common accessory ossicle. In this article, we describe an outcome of a bipartite talus fragment removal due to tarsal tunnel syndrome and illustrate a rare pathological consequence of a bipartite talus. We further highlight the importance of early surgical management in patients presenting with an identifiable structure contributing to tibial nerve compression.


Assuntos
Deformidades Congênitas das Extremidades Inferiores , Tálus , Síndrome do Túnel do Tarso , Humanos , Artralgia , Descompressão Cirúrgica
4.
Surg Endosc ; 38(3): 1556-1567, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38151678

RESUMO

BACKGROUND: Preliminary evidence demonstrates female surgeons have improved post-operative outcomes compared to male colleagues despite underrepresentation in surgery. This study explores the effect of patient-surgeon gender discordance on outcomes in three specialties with high female patient populations: bariatric, foregut, colorectal. METHODS: This is a retrospective study using the New York State (NYS) SPARCS database and first study evaluating outcomes based on surgeon/patient concordance in NYS. Bariatric, foregut, and colorectal surgery cases from 2013 to 2017 were identified. RESULTS: Bariatric: female patients (FP) with CC had lower 30-day readmissions but higher complications compared with DC. Male patients (MP) with CC trended towards higher 30-day readmissions but lower complications compared with DC. FP received significantly better influence from CC in 30-day readmission, but disadvantages in complications. There was no significant difference in LOS or ED visits between CC and DC groups for either FP or MP. Foregut: FP with CC had lower LOS, 30-day readmissions, and 30-day ED visits compared with DC. MP showed opposite trends between CC and DC, although non-significant. The benefit from concordance was pronounced in FP compared to MP in LOS, 30-day readmissions, and 30-day ED visit. Concordance vs discordance did not significantly affect complications within either FP or MP group. Colorectal: the difference between CC and DC was not significant within FP or MP groups in any outcomes. When comparing the difference of 30-day readmissions in CC vs DC between FP and MP, there is a significant difference. CONCLUSION(S): Overall, our results show DC between patient and surgeon has significant effect on patient outcomes. A negative effect is seen for female patients in certain specialties, most pronounced in foregut surgery. This emphasizes need for surgeons to be conscious of care provided to opposite gender patients and underscores increasing female surgeons in high FP fields.


Assuntos
Neoplasias Colorretais , Complicações Pós-Operatórias , Humanos , Masculino , Feminino , New York , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Readmissão do Paciente , Resultado do Tratamento
5.
Biology (Basel) ; 12(7)2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37508394

RESUMO

Common bean (Phaseolus vulgaris L.) is an important crop for food security and for national economics for several countries worldwide. One of the most important factors of risk in common bean production is the fungal disease anthracnose caused by Colletotrichum lindemuthianum, which, in some cases, causes complete yield losses; this kind of plant disease is usually managed through the application of chemical products such as fungicides that are commonly not accepted by society. This rejection is based on the relationship of pesticides with health damage and environmental contamination. In order to help in solving these drawbacks, the present work proposes the use of electrochemically activated salt solutions (EASSs) as a safer pathogen control agent in crops, due to it having shown an elicitor and biostimulant effect on plants. With this background, this manuscript presents in vitro results of the evaluation of the inhibitory effect for multiple bean pathogens and in vivo results of EASS in the common bean-Colletotrichum pathosystem by evaluation of the infection severity and defense activation, such as secondary metabolite production and antioxidant activity. EASS presence in growth media had a strong inhibitory effect at the beginning of experiments for some of the evaluated fungi. EASSs showed an effect against the development of the disease when applied in specific doses to prevent distress in plants.

6.
Redox Biol ; 61: 102630, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36796135

RESUMO

Type 2 diabetes mellitus (T2D) affects millions of people worldwide and is one of the leading causes of morbidity and mortality. The skeletal muscle (SKM) is one of the most important tissues involved in maintaining glucose homeostasis and substrate oxidation, and it undergoes insulin resistance in T2D. In this study, we identify the existence of alterations in the expression of mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) in skeletal muscle from two different forms of T2D: early-onset type 2 diabetes (YT2) (onset of the disease before 30 years of age) and the classical form of the disease (OT2). GSEA analysis from microarray studies revealed the repression of mitochondrial mt-aaRSs independently of age, which was validated by real-time PCR assays. In agreement with this, a reduced expression of several encoding mt-aaRSs was also detected in skeletal muscle from diabetic (db/db) mice but not in obese ob/ob mice. In addition, the expression of the mt-aaRSs proteins most relevant in the synthesis of mitochondrial proteins, threonyl-tRNA, and leucyl-tRNA synthetases (TARS2 and LARS2) were also repressed in muscle from db/db mice. It is likely that these alterations participate in the reduced expression of proteins synthesized in the mitochondria detected in db/db mice. We also document an increased iNOS abundance in mitochondrial-enriched muscle fractions from diabetic mice that may inhibit aminoacylation of TARS2 and LARS2 by nitrosative stress. Our results indicate a reduced expression of mt-aaRSs in skeletal muscle from T2D patients, which may participate in the reduced expression of proteins synthesized in mitochondria. An enhanced mitochondrial iNOS could play a regulatory role in diabetes.


Assuntos
Aminoacil-tRNA Sintetases , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Camundongos , Animais , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Experimental/metabolismo , Regulação para Baixo , Aminoacil-tRNA Sintetases/genética , Mitocôndrias/metabolismo , Músculo Esquelético/metabolismo , RNA de Transferência/metabolismo
7.
Plants (Basel) ; 11(24)2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36559556

RESUMO

Agriculture needs to decrease the use of agrochemicals due to their high toxicity and adopt new strategies to achieve sustainable food production. Therefore, nanoparticles (NPs) and plant growth-promoting bacteria (PGPB) have been proposed as viable strategies to obtain better crop yields with less environmental impact. Here, we describe the effect of silica nanoparticles (SiO2-NPs) on survival, antioxidant enzymatic activity, phosphate solubilization capacity, and gibberellin production of Bacillus cereus-Amazcala (B.c-A). Moreover, the effect of the co-application of SiO2-NPs and B.c-A on seed germination, physiological characteristics, and antioxidant enzymatic activity of chili pepper plants was investigated under greenhouse conditions. The results indicated that SiO2-NPs at 100 ppm enhanced the role of B.c-A as PGPB by increasing its phosphate solubilization capacity and the production of GA7. Moreover, B.c-A catalase (CAT) and superoxide dismutase (SOD) activities were increased with SiO2-NPs 100 ppm treatment, indicating that SiO2-NPs act as a eustressor, inducing defense-related responses. The co-application of SiO2-NPs 100 ppm and B.c-A improved chili pepper growth. There was an increase in seed germination percentage, plant height, number of leaves, and number and yield of fruits. There was also an increase in CAT and PAL activities in chili pepper plants, indicating that bacteria-NP treatment induces plant immunity.

8.
Acta Crystallogr E Crystallogr Commun ; 78(Pt 9): 905-911, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36072516

RESUMO

The crystal structures of ligand precursor bis-(imidazolium) salts 1,1'-methyl-enebis(3-tert-butyl-imidazolium) dibromide monohydrate, C15H26N4 +·2Br-·H2O or [ tBuNHC2Me][Br]2·H2O, 1,1'-(ethane-1,2-di-yl)bis-(3-tert-butyl-imidazolium) dibromide dihydrate, C16H28N4 +·2Br-·2H2O or [ tBuNHC2Et][Br]2·2H2O, 1,1'-methyl-enebis[3-(2,4,6-tri-methyl-phen-yl)imidazolium] dibromide dihydrate, C25H30N4 2+·2Br-·2H2O or [MesNHC2Me][Br]2·2H2O, and 1,1'-(ethane-1,2-di-yl)bis-[3-(2,4,6-tri-methyl-phen-yl)imidazolium] dibromide tetra-hydrate, C26H32N4 2+·2Br-·4H2O or [MesNHC2Et][Br]2·4H2O, are reported. At 293 K, [ tBuNHC2Me][Br]2·H2O crystallizes in the P21/c space group, while [ tBuNHC2Et][Br]2·2H2O crystallizes in the P21/n space group at 100 K. At 112 K, [MesNHC2Me][Br]2·2H2O crystallizes in the ortho-rhom-bic space group Pccn while [MesNHC2Et][Br]2·4H2O crystallizes in the P21/c space group at 100 K. Bond distances and angles within the imidazolium rings are generally comparable among the four structures. All four bis-(imidazolium) salts co-crystallize with one to four mol-ecules of water.

9.
J Neurosurg Pediatr ; : 1-6, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36087318

RESUMO

OBJECTIVE: Many pathways to positions of leadership exist within pediatric neurological surgery. The authors sought to investigate common trends in leadership among pediatric neurosurgery fellowship directors (FDs) and describe how formalized pediatric neurosurgical training arrived at its current state. METHODS: Fellowship programs were identified using the Accreditation Council for Pediatric Neurosurgery Fellowships website. Demographic, training, membership, and research information was collected via email, telephone, curricula vitae, and online searches. RESULTS: The authors' survey was sent to all 35 identified FDs, and 21 responses were received. Response data were supplemented with curricula vitae and online data prior to analysis. FDs were predominantly male, self-identified predominantly as Caucasian, and had a mean age of 53 years. The mean duration from residency graduation until FD appointment was 13.4 years. The top training programs to produce future FDs were New York University and Washington University in St. Louis (residency) and Washington University in St. Louis (fellowship). CONCLUSIONS: This study characterizes the current state of pediatric neurosurgery fellowship program leadership. The data serve as an important point of reference to compare with future leadership as well as contrast with neurosurgery and other surgical disciplines in general.

10.
Ecol Evol ; 12(8): e9133, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35923937

RESUMO

Invasive Alien Species (IAS) alter ecosystems, disrupting ecological processes and driving the loss of ecosystem services. The common carp Cyprinus carpio is a hazardous and widespread IAS, becoming the most abundant species in many aquatic ecosystems. This species transforms ecosystems by accumulating biomass to the detriment of other species, thus altering food webs. However, some terrestrial species, such as vertebrate scavengers, may benefit from dead carps, by incorporating part of the carp biomass into the terrestrial environment. This study describes the terrestrial vertebrate scavenger assemblage that benefits from carp carcasses in a Mediterranean wetland. We also evaluate the seasonal differences in the scavenger assemblage composition and carrion consumption patterns. Eighty carp carcasses (20 per season) were placed in El Hondo Natural Park, a seminatural mesohaline wetland in south-eastern Spain, and we monitored their consumption using camera traps. We recorded 14 scavenger species (10 birds and four mammals) consuming carp carcasses, including globally threatened species. Vertebrates consumed 73% of the carrion biomass and appeared consuming at 82% of the carcasses. Of these carcasses consumed, 75% were completely consumed and the mean consumption time of carcasses completely consumed by vertebrates was 44.4 h (SD = 42.1 h). We recorded differences in species richness, abundance, and assemblage composition among seasons, but we did not find seasonal differences in consumption patterns throughout the year. Our study recorded a rich and efficient terrestrial vertebrate scavenger assemblage benefitting from carp carcasses. We detected a seasonal replacement on the scavenger species, but a maintenance of the ecological function of carrion removal, as the most efficient carrion consumers were present throughout the year. The results highlight the importance of vertebrate scavengers in wetlands, removing possible infectious focus, and moving nutrients between aquatic and terrestrial environments.

12.
J Cell Sci ; 135(12)2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35638575

RESUMO

Mitotic kinesin-like protein 2 (MKLP2; also known as KIF20A) is a motor protein with a well-established function in promoting cytokinesis. However, our results with siRNAs targeting MKLP2 and small-molecule inhibitors of MKLP2 (MKLP2i) suggest that it also has a function earlier in mitosis, prior to anaphase. In this study, we provide direct evidence that MKLP2 facilitates chromosome congression in prometaphase. We employed live imaging to observe HeLa cells with fluorescently tagged histones treated with MKLP2i and discovered a pronounced chromosome congression defect. We show that MKLP2 facilitates error correction, as inhibited cells have a significant increase in unstable, syntelic kinetochore-microtubule attachments. We find that the aberrant attachments are accompanied by elevated Aurora kinase (A and B) activity and phosphorylation of the downstream target HEC1 (also known as NDC80) at Ser55. Finally, we show that MKLP2 inhibition results in aneuploidy, confirming that MKLP2 safeguards cells against chromosomal instability. This article has an associated First Person interview with the first author of the paper.


Assuntos
Cinesinas/metabolismo , Mitose , Aurora Quinase B/genética , Aurora Quinase B/metabolismo , Segregação de Cromossomos , Cromossomos/metabolismo , Células HeLa , Humanos , Cinesinas/genética , Cinetocoros/metabolismo , Microtúbulos/metabolismo , Mitose/genética , Fuso Acromático/metabolismo
13.
Bioinformatics ; 38(10): 2934-2936, 2022 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-35561195

RESUMO

SUMMARY: High-throughput sequencing of transfer RNAs (tRNA-Seq) is a powerful approach to characterize the cellular tRNA pool. Currently, however, analyzing tRNA-Seq datasets requires strong bioinformatics and programming skills. tRNAstudio facilitates the analysis of tRNA-Seq datasets and extracts information on tRNA gene expression, post-transcriptional tRNA modification levels, and tRNA processing steps. Users need only running a few simple bash commands to activate a graphical user interface that allows the easy processing of tRNA-Seq datasets in local mode. Output files include extensive graphical representations and associated numerical tables, and an interactive html summary report to help interpret the data. We have validated tRNAstudio using datasets generated by different experimental methods and derived from human cell lines and tissues that present distinct patterns of tRNA expression, modification and processing. AVAILABILITY AND IMPLEMENTATION: Freely available at https://github.com/GeneTranslationLab-IRB/tRNAstudio under an open-source GNU GPL v3.0 license. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
RNA de Transferência , Software , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Processamento Pós-Transcricional do RNA , RNA de Transferência/genética , Análise de Sequência de RNA/métodos
14.
J Clin Med ; 11(4)2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35207278

RESUMO

Introduction and objective: Assessing the abuse potential of new substances with central nervous system activity is essential for preventing possible risks of misuse and addiction. The same methodology is recommended for the evaluation of the abuse potential of recreational drugs. This systematic review aims to assess the pharmacological effects related to the abuse potential and pharmacokinetics of cathinones, which are evaluated in both experimental and prospective observational studies in humans. Materials and Methods: A systematic search of the published literature was conducted to retrieve studies that had administered cathinone, mephedrone, methylone, and diethylpropion to evaluate their acute pharmacological effects related to abuse potential. Results: The search yielded 583 results, 18 of which were included to assess the abuse potential of cathinone (n = 5), mephedrone (n = 7), methylone (n = 1), and diethylpropion (n = 5). All four substances induce stimulant and euphorigenic effects that resemble those of amphetamines and MDMA, and their different intensities may be associated with varying levels of abuse potential. Conclusions: Cathinone, mephedrone, methylone, and diethylpropion induce a range of desirable and reinforcing effects that may, to some extent, result in abuse potential. Further investigation is needed to minimize and prevent their impact on society and public health.

15.
Rev. méd. Panamá ; 41(3): 76-76, dic 2021.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1371943

RESUMO

Se presenta el caso de un paciente con historia de fiebre no cuantificada y disnea de 1 semana de evolución, que posteriormente al realizarle la prueba de COVID-19, sale positivo. Refiere además presentar 2 meses de evolución de aumento del volumen testicular del lado izquierdo, sin ninguna otra sintomatología. En el ultrasonido testicular, se evidencia una masa que ocupa la mayor parte de la bolsa testicular izquierda, de eco textura heterogénea. La tomografía de tórax, abdomen y pelvis contrastada, se observa derrame pleural bilateral con múltiples adenopatías mediastinales, abdominales y pélvicas, así como múltiples metástasis a distancia.   (provisto por Infomedic International)


We present the case of a patient with a history of unquantified fever and dyspnea of 1 week of evolution, who subsequently tested positive for COVID-19. He also reports presenting 2 months of evolution of increased testicular volume on the left side, without any other symptomatology. In the testicular ultrasound, there is evidence of a mass that occupies most of the left testicular pouch, of heterogeneous echo texture. Contrast tomography of the chest, abdomen and pelvis showed bilateral pleural effusion with multiple mediastinal, abdominal and pelvic adenopathies, as well as multiple distant metastases. (provided by Infomedic International)

17.
Biology (Basel) ; 10(10)2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34681122

RESUMO

Agricultural systems face several challenges in terms of meeting everyday-growing quantities and qualities of food requirements. However, the ecological and social trade-offs for increasing agricultural production are high, therefore, more sustainable agricultural practices are desired. Researchers are currently working on diverse sustainable techniques based mostly on natural mechanisms that plants have developed along with their evolution. Here, we discuss the potential agricultural application of extracellular DNA (eDNA), its multiple functioning mechanisms in plant metabolism, the importance of hormetic curves establishment, and as a challenge: the technical limitations of the industrial scale for this technology. We highlight the more viable natural mechanisms in which eDNA affects plant metabolism, acting as a damage/microbe-associated molecular pattern (DAMP, MAMP) or as a general plant biostimulant. Finally, we suggest a whole sustainable system, where DNA is extracted from organic sources by a simple methodology to fulfill the molecular characteristics needed to be applied in crop production systems, allowing the reduction in, or perhaps the total removal of, chemical pesticides, fertilizers, and insecticides application.

18.
J Biol Chem ; 297(4): 101184, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34509474

RESUMO

The deubiquitinating enzyme USP37 is known to contribute to timely onset of S phase and progression of mitosis. However, it is not clear if USP37 is required beyond S-phase entry despite expression and activity of USP37 peaking within S phase. We have utilized flow cytometry and microscopy to analyze populations of replicating cells labeled with thymidine analogs and monitored mitotic entry in synchronized cells to determine that USP37-depleted cells exhibited altered S-phase kinetics. Further analysis revealed that cells depleted of USP37 harbored increased levels of the replication stress and DNA damage markers γH2AX and 53BP1 in response to perturbed replication. Depletion of USP37 also reduced cellular proliferation and led to increased sensitivity to agents that induce replication stress. Underlying the increased sensitivity, we found that the checkpoint kinase 1 is destabilized in the absence of USP37, attenuating its function. We further demonstrated that USP37 deubiquitinates checkpoint kinase 1, promoting its stability. Together, our results establish that USP37 is required beyond S-phase entry to promote the efficiency and fidelity of replication. These data further define the role of USP37 in the regulation of cell proliferation and contribute to an evolving understanding of USP37 as a multifaceted regulator of genome stability.


Assuntos
Quinase 1 do Ponto de Checagem/metabolismo , Endopeptidases/metabolismo , Fase S , Quinase 1 do Ponto de Checagem/genética , Dano ao DNA , Replicação do DNA , Endopeptidases/genética , Estabilidade Enzimática , Instabilidade Genômica , Células HCT116 , Células HeLa , Histonas , Humanos , Células MCF-7 , Ubiquitinação
19.
Nucleic Acids Res ; 49(12): 7011-7034, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34125917

RESUMO

The modification of adenosine to inosine at the wobble position (I34) of tRNA anticodons is an abundant and essential feature of eukaryotic tRNAs. The expansion of inosine-containing tRNAs in eukaryotes followed the transformation of the homodimeric bacterial enzyme TadA, which generates I34 in tRNAArg and tRNALeu, into the heterodimeric eukaryotic enzyme ADAT, which modifies up to eight different tRNAs. The emergence of ADAT and its larger set of substrates, strongly influenced the tRNA composition and codon usage of eukaryotic genomes. However, the selective advantages that drove the expansion of I34-tRNAs remain unknown. Here we investigate the functional relevance of I34-tRNAs in human cells and show that a full complement of these tRNAs is necessary for the translation of low-complexity protein domains enriched in amino acids cognate for I34-tRNAs. The coding sequences for these domains require codons translated by I34-tRNAs, in detriment of synonymous codons that use other tRNAs. I34-tRNA-dependent low-complexity proteins are enriched in functional categories related to cell adhesion, and depletion in I34-tRNAs leads to cellular phenotypes consistent with these roles. We show that the distribution of these low-complexity proteins mirrors the distribution of I34-tRNAs in the phylogenetic tree.


Assuntos
Inosina/metabolismo , Biossíntese de Proteínas , RNA de Transferência/metabolismo , Adenosina Desaminase/genética , Adesão Celular , Processos de Crescimento Celular , Linhagem Celular , Códon , Eucariotos/genética , Feminino , Células HEK293 , Humanos , Domínios Proteicos/genética , Inibidores da Síntese de Proteínas/farmacologia , RNA Mensageiro/metabolismo , RNA de Transferência/química , Ribossomos/metabolismo
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