RESUMO
Read-through chimeric RNAs are being recognized as a means to expand the functional transcriptome and contribute to cancer tumorigenesis when mis-regulated. However, current software tools often fail to predict them. We have developed RTCpredictor, utilizing a fast ripgrep tool to search for all possible exon-exon combinations of parental gene pairs. We also added exonic variants allowing searches containing common SNPs. To our knowledge, it is the first read-through chimeric RNA specific prediction method that also provides breakpoint coordinates. Compared with 10 other popular tools, RTCpredictor achieved high sensitivity on a simulated and three real datasets. In addition, RTCpredictor has less memory requirements and faster execution time, making it ideal for applying on large datasets.
Assuntos
Análise de Sequência de RNA , Software , Análise de Sequência de RNA/métodos , Humanos , RNA/genética , Biologia Computacional/métodos , Éxons , Algoritmos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Hormonal contraceptives are a popular option for pregnancy prevention and other indications and require a prescription. Since 2013, 24 states have given pharmacists legal authority to initiate self-administered hormonal contraceptives, allowing for direct pharmacy access (DPA). New York State (NYS) did not allow for DPA of any hormonal contraceptives during the survey period, but passed a bill in 2023 allowing pharmacists to dispense hormonal contraceptives in accordance with a nonpatient-specific order. OBJECTIVES: This study aimed to characterize the experiences, perceptions, and knowledge of access to and DPA to hormonal contraceptives. METHODS: A survey was developed to gather responses to demographic- and opinion-related questions and administered online using the Pollfish survey platform. Participants were women between the ages of 16 and 44 years who lived in NYS. To ensure geographic representation, at least one response was gathered from each of the 27 NYS congressional districts. Chi-square tests were used to assess differences in hormonal contraceptive use by patient demographics. RESULTS: Most of the 500 respondents reported past (76.2%) or current/planned (76.8%) use of hormonal contraceptives. Older age (P = 0.033) and higher income (P = 0.0016) were associated with significantly greater rates of use. The most common challenges when visiting a provider for birth control included needing to schedule an appointment and wait times at the provider. Almost three-quarters of respondents (72.6%) were not aware that pharmacists could initiate contraceptives in other states, and 74.2% reported feeling comfortable with a pharmacist prescribing and dispensing hormonal contraceptives. CONCLUSION: Contraceptive initiation by pharmacists would be acceptable to most respondents, but there is room for increased acceptance based on patient education and experience. DPA to hormonal contraceptives may eliminate some of the barriers identified in this survey.
Assuntos
Anticoncepcionais , Farmácia , Gravidez , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Masculino , Farmacêuticos , New York , Anticoncepção , Anticoncepcionais Orais HormonaisRESUMO
Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue cancer with a survival rate below 27% for high-risk children despite aggressive multi-modal therapeutic interventions. After decades of research, no targeted therapies are currently available. Therapeutically targeting actin-binding proteins, although promising, has historically been challenging. Recent advances have made this possibility more salient, including our lab's identification of advillin (AVIL), a novel oncogenic actin-binding protein that plays a role in many cytoskeletal functions. AVIL is overexpressed in many RMS cell lines, patient-derived xenograft models, and a cohort of 30 clinical samples of both the alveolar (ARMS) and embryonal (ERMS) subtypes. Overexpression of AVIL in mesenchymal stem cells induces neoplastic transformation both in vitro and in vivo, and reversing overexpression through genetic modulation reverses the transformation. This suggests a critical role of AVIL in RMS tumorigenesis and maintenance. As an actin-binding protein, AVIL would not traditionally be considered a druggable target. This perspective will address the feasibility of targeting differentially expressed actin-binding proteins such as AVIL therapeutically, and how critical cell infrastructure can be damaged in a cancer-specific manner.
Assuntos
Proteínas dos Microfilamentos , Rabdomiossarcoma , Criança , Humanos , Proteínas dos Microfilamentos/genética , Rabdomiossarcoma/genética , Citoesqueleto , Agressão , Transformação Celular Neoplásica , FeniraminaRESUMO
OBJECTIVE: To review data of elagolix plus estradiol and norethindrone acetate as add-back therapy for the treatment of heavy menstrual bleeding (HMB) in premenopausal women with uterine fibroids. DATA SOURCES: Literature search of PubMed/MEDLINE and SCOPUS was performed using the search terms Oriahnn; elagolix, estradiol, norethindrone AND heavy menstrual bleeding; elagolix AND heavy menstrual bleeding; and gonadotropin-releasing hormone receptor antagonist AND heavy menstrual bleeding between January 1, 1996, to March 2, 2021. Additional data were obtained from prescribing information, references of identified articles, and abstracts from scientific meetings. STUDY SELECTION/DATA EXTRACTION: Clinical trials and articles discussing elagolix plus add-back therapy for the management of HMB in women with leiomyomas were included. DATA SYNTHESIS: Phase 3 trials met the primary end point of menstrual blood loss (MBL) less than 80 mL at month 6 and at least a 50% reduction in MBL from baseline to the final month in 68.5% of women taking elagolix plus add-back therapy enrolled in UF-1 (8.7% placebo) and 76.5% of women in UF-2 (10% placebo). The most common adverse effects include hot flushes, nausea, headache, and night sweats. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Women with symptomatic uterine fibroids can experience significant HMB resulting in distress, depression, and anxiety. Surgical intervention remains the most commonly recommended and chosen treatment. Elagolix plus add-back therapy is a nonsurgical, oral option. CONCLUSIONS: Elagolix plus add-back therapy is effective in reducing menstrual bleeding associated with uterine fibroids. However, there are several warnings and precautions that must be considered.
Assuntos
Leiomioma , Menorragia , Preparações Farmacêuticas , Neoplasias Uterinas , Feminino , Hormônio Liberador de Gonadotropina , Humanos , Leiomioma/complicações , Leiomioma/tratamento farmacológico , Menorragia/tratamento farmacológico , Menorragia/etiologia , Neoplasias Uterinas/complicações , Neoplasias Uterinas/tratamento farmacológicoRESUMO
BACKGROUND: Several states have passed legislation allowing pharmacists to prescribe hormonal contraceptives in an effort to expand access to family planning options for patients. OBJECTIVE: The primary objective of this research is to evaluate participant knowledge and perception, attitudes, and preparedness regarding pharmacist-prescribed hormonal contraception before and after completion of the American Pharmacists Association's interactive online training program, "Increasing Access to Hormonal Contraceptive Products: A Training Program for Pharmacists." METHODS: Training program participants were assessed on their knowledge after each module, and they were invited to participate in a pre- and postsurvey about practice environments and opinions related to hormonal contraceptive prescribing. Descriptive statistics were calculated for categorical survey responses, and means and standard deviations were calculated for program knowledge assessment scores. Pre- and postsurvey responses were analyzed using the Wilcoxon signed-rank test or McNemar's test according to the type of response options. RESULTS: More than 450 participants completed the Hormonal Contraception Training Program; 61% completed the presurvey and 39% completed the postsurvey. Participants had an average score of 86% across modules for both surveys. Comfort level increased statistically significantly in all areas surveyed after program completion. Survey results identified statistically significant changes between pre- and postsurvey in the belief that pharmacists are trained and educated to counsel on and initiate hormonal contraceptives (P < 0.001 and P < 0.001) and that prescribing hormonal contraceptives should be within a pharmacist's scope of practice (P < 0.001). Most respondents (83%) agreed that pharmacy schools should expand content on contraceptive prescribing, although more than half (56%) reported that their pharmacy school taught them the requisite hormonal contraceptive clinical content. CONCLUSION: Training programs play an important role in preparing pharmacists for prescribing roles by providing knowledge and increasing confidence and generally positively affecting perceptions of and attitudes toward prescribing hormonal contraceptives.
Assuntos
Anticoncepcionais , Farmacêuticos , Contracepção Hormonal , Humanos , Inquéritos e Questionários , Estados UnidosRESUMO
Glioblastoma (GBM) is the most common adult neural malignancy and the deadliest. The standard of care is optimal, safe, cytoreductive surgery followed by combined radiation therapy and alkylating chemotherapy with temozolomide. Recurrence is common and therapeutic options in the recurrent setting are limited. The dismal prognosis of GBM has led to novel treatments being a serious roadblock in the field, with most new treatments failing to show efficacy. Targeted therapies have shown some success in many cancers, but GBM remains one of the most difficult to treat, especially in recurrence. New chemotherapeutic directions need to be explored, possibly expanding the targeted chemotherapy spectrum in previously unforeseen ways. In this perspective paper, we will explain why AVIL, an actin-binding protein recently found to be overexpressed in GBM and a driving force for GBM, could prove versatile in the fight against cancer. By looking at AVIL and its potential to regulate FOXM1 and LIN28B, we will be able to highlight a way to improve outcomes for GBM patients who normally have very little hope.
Assuntos
Citoesqueleto/metabolismo , Glioblastoma/metabolismo , Proteínas dos Microfilamentos/antagonistas & inibidores , Proteína Forkhead Box M1 , Glioblastoma/tratamento farmacológico , Humanos , Proteínas dos Microfilamentos/metabolismo , Proteínas de Ligação a RNARESUMO
Muscle-specific E3 ubiquitin ligases have been identified in muscle atrophy-inducing conditions. The purpose of the current study was to explore the functional role of F-box and leucine-rich protein 22 (Fbxl22), and a newly identified splice variant (Fbxl22-193), in skeletal muscle homeostasis and neurogenic muscle atrophy. In mouse C2C12 muscle cells, promoter fragments of the Fbxl22 gene were cloned and fused with the secreted alkaline phosphatase reporter gene to assess the transcriptional regulation of Fbxl22. The tibialis anterior muscles of male C57/BL6 mice (12-16 wk old) were electroporated with expression plasmids containing the cDNA of two Fbxl22 splice variants and tissues collected after 7, 14, and 28 days. Gastrocnemius muscles of wild-type and muscle-specific RING finger 1 knockout (MuRF1 KO) mice were electroporated with an Fbxl22 RNAi or empty plasmid and denervated 3 days posttransfection, and tissues were collected 7 days postdenervation. The full-length gene and novel splice variant are transcriptionally induced early (after 3 days) during neurogenic muscle atrophy. In vivo overexpression of Fbxl22 isoforms in mouse skeletal muscle leads to evidence of myopathy/atrophy, suggesting that both are involved in the process of neurogenic muscle atrophy. Knockdown of Fbxl22 in the muscles of MuRF1 KO mice resulted in significant additive muscle sparing 7 days after denervation. Targeting two E3 ubiquitin ligases appears to have a strong additive effect on protecting muscle mass loss with denervation, and these findings have important implications in the development of therapeutic strategies to treat muscle atrophy.
Assuntos
Proteínas F-Box/genética , Proteínas Musculares/genética , Atrofia Muscular/genética , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genética , Animais , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Camundongos , Camundongos Knockout , Células Musculares/metabolismo , Células Musculares/patologia , Músculo Esquelético/inervação , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/fisiopatologia , TransfecçãoRESUMO
Exceptionally low river flows are predicted to become more frequent and more severe across many global regions as a consequence of climate change. Investigations of trace metal transport dynamics across streamflows reveal stark changes in water chemistry, metal transformation processes, and remediation effectiveness under exceptionally low-flow conditions. High spatial resolution hydrological and water quality datasets indicate that metal-rich groundwater will exert a greater control on stream water chemistry and metal concentrations because of climate change. This is because the proportion of stream water sourced from mined areas and mineralized strata will increase under predicted future low-flow scenarios (from 25% under Q45 flow to 66% under Q99 flow in this study). However, mineral speciation modelling indicates that changes in stream pH and hydraulic conditions at low flow will decrease aqueous metal transport and increase sediment metal concentrations by enhancing metal sorption directly to streambed sediments. Solute transport modelling further demonstrates how increases in the importance of metal-rich diffuse groundwater sources at low flow could minimize the benefits of point source metal contamination treatment. Understanding metal transport dynamics under exceptionally low flows, as well as under high flows, is crucial to evaluate ecosystem service provision and remediation effectiveness in watersheds under future climate change scenarios.
Assuntos
Água Subterrânea , Poluentes Químicos da Água , Ecossistema , Rios , Poluentes Químicos da Água/análise , Qualidade da ÁguaRESUMO
Objective: To review data regarding bremelanotide, a recently approved therapy for hypoactive sexual desire disorder (HSDD). Data Sources: Literature search of Medline, SCOPUS, and EMBASE was performed using the search terms bremelanotide, bremelanotide injection, Vyleesi, and melanocortin 4 receptor agonist between January 1, 1996, and December 15, 2019. Reference lists from included articles were also reviewed for pertinent citations. Study Selection/Data Extraction: We included phase 2 and 3 trials of bremelanotide. There were 2 reports of phase 3 trials and 2 reports of phase 2 trials. Additional information from supplementary analyses was also referenced. Data Synthesis: Bremelanotide demonstrates significant improvement in desire and a significant decrease in distress related to lack of desire. The most common adverse effects include nausea (39.9%), facial flushing (20.4%), and headache (11%). Relevance to Patient Care and Clinical Practice: Bremelanotide is the second Food and Drug Administration-approved medication for the treatment of HSDD. Bremelanotide's place in therapy is unknown, as the HSDD guidelines were last updated in 2017. Although the trials met statistical significance for change in sexual desire elements and distress related to sexual desire, the clinical benefit may only be modest. Conclusion: Bremelanotide is a subcutaneous injection that can be administered as needed approximately 45 minutes prior to sexual activity. Bremelanotide is safe and has limited drug-drug interactions, including no clinically significant interactions with ethanol. Prescribing guidelines recommend no more than 1 dose in 24 hours and no more than 8 doses per month. Individuals should discontinue use after 8 weeks without benefit.
Assuntos
Libido/efeitos dos fármacos , Peptídeos Cíclicos/uso terapêutico , Disfunções Sexuais Psicogênicas/tratamento farmacológico , alfa-MSH/uso terapêutico , Ensaios Clínicos como Assunto , Interações Medicamentosas , Feminino , Humanos , Injeções Subcutâneas , Náusea/induzido quimicamente , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/efeitos adversos , Peptídeos Cíclicos/farmacocinética , Receptor Tipo 3 de Melanocortina/agonistas , Receptor Tipo 4 de Melanocortina/agonistas , Resultado do Tratamento , alfa-MSH/administração & dosagem , alfa-MSH/efeitos adversos , alfa-MSH/farmacocinéticaRESUMO
Skeletal muscle atrophy is a debilitating condition that can arise due to aging, cancer, corticosteroid use, and denervation. To better characterize the molecular genetic events of neurogenic atrophy, a previous study analyzed gene expression patterns in gastrocnemius muscle following sciatic nerve transection and found for the first time that Zinc Finger Protein 593 (Zfp593) is expressed in skeletal muscle and is induced in response to denervation. Quantitative PCR and Western blot analyses confirmed that Zfp593 is expressed in both proliferating myoblasts and differentiated myotubes. To assess sub-cellular location, GFP-tagged Zfp593 was expressed in C2C12â¯cells and found to localize to the nucleus. The Zfp593 protein possesses a putative zinc finger domain and is believed to function as a modulator of the Oct-2 transcription factor. Interestingly, ectopic expression of Zfp593 did not affect the ability of Oct-1 or Oct-2 to inhibit an Oct reporter gene in muscle cells. Finally, Zfp593 overexpression in cultured muscle cells resulted in significant repression of muscle cell differentiation and attenuation of ERK1/2 and p38 phosphorylation, but did not vitiate protein synthesis. The discovery that Zfp593 is expressed in skeletal muscle combined with the observation that it is induced in response to neurogenic atrophy furthers our understanding of the molecular genetic events of muscle wasting.
Assuntos
Diferenciação Celular/genética , Proteínas de Ligação a DNA/genética , Desenvolvimento Muscular/genética , Atrofia Muscular/genética , Mioblastos/fisiologia , Fatores de Transcrição/genética , Animais , Células Cultivadas , Sistema de Sinalização das MAP Quinases/genética , Camundongos , Músculo Esquelético/patologia , Músculo Esquelético/fisiologia , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Regulação para Cima/genética , Dedos de Zinco/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
OBJECTIVES: Empowering pharmacists to prescribe contraceptives could help alleviate barriers such as the accessibility of medical centers and the availability, inconvenience, and cost of appointments. Several states have enacted legislation authorizing pharmacists to prescribe hormonal contraceptives. This manuscript provides an overview of each of the states' laws and highlights differences among the states. The objectives of this study were to (1) list the states in which pharmacists currently have the authority to prescribe contraceptives and (2) compare the differences among those states. DATA SOURCES: The authors assembled state statutes and regulations on pharmacist prescribing of contraceptives and conducted a literature review for research on pharmacist prescribing of contraceptives using PubMed. SUMMARY: Nine states, plus the District of Columbia, authorize pharmacists to prescribe hormonal contraceptives autonomously under a statewide authority, and each state differs in their policy. CONCLUSION: For pharmacists to take full advantage of this opportunity and to expand their clinical role, the quality, consistency, and sustainability of these initiatives must be assessed.
Assuntos
Contracepção Hormonal , Farmacêuticos , Atitude do Pessoal de Saúde , Anticoncepção , Prescrições de Medicamentos , Acessibilidade aos Serviços de Saúde , HumanosRESUMO
OBJECTIVE: With the rise in electronic cigarette (ENDS) use among US young adults, more research is needed on expectations for use and perceptions related to body image, weight control, and stress relief. METHODS: College students (N = 230; modal age 21 years; 68% female) completed an online survey assessing cigarette smoking and ENDS, dieting and body image, perceptions about flavors, stress, weight gain prevention, and appetite regulation. SAMPLE CHARACTERISTICS: Dual use (cigarette and ENDS) was reported by n = 69 (30.0%). Exclusive cigarette smoking was endorsed by n = 53 (23%) with exclusive ENDS use reported by n = 15 (6.5%). Ninety-three participants (40.5%) reported not using either product. RESULTS: Among those using ENDS, < 33% reported using as a stress management tool, < 15% reported using ENDS to control appetite, and > 70% reported using cartridges that tasked like sweets. There was a positive correlation between dieting behaviors and body concern, suggesting those who reported higher use of ENDS for weight and appetite regulation also had higher pathological eating scores and concern over body shape and size. CONCLUSION: Prevention and education related to weight, body image, and tobacco are needed to address misperceptions of tobacco products. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.
Assuntos
Imagem Corporal/psicologia , Fumar Cigarros/psicologia , Comportamento Alimentar/psicologia , Estresse Psicológico/psicologia , Vaping/psicologia , Apetite , Atitude Frente a Saúde , Peso Corporal , Fumar Cigarros/epidemiologia , Estudos Transversais , Dieta , Sistemas Eletrônicos de Liberação de Nicotina , Feminino , Humanos , Masculino , Estudantes , Inquéritos e Questionários , Universidades , Vaping/epidemiologia , Adulto JovemRESUMO
In recent years there has been increasing interest in the use of selenised yeast (Se-Y) as an antioxidant feed supplement. Here, three selenised yeast products are differentiated in terms of bioefficiency and the ameliorative effect on Cadmium (Cd) toxicity in porcine epithelial cells. A porcine digestion in vitro model was chosen to more accurately simulate the bioavailability of different Se-Y preparations, allowing a comprehensive understanding of the bio efficiency of each Se-Y compound in the porcine model. To elucidate a possible mechanism of action of selenium a number of bioassays were applied. Levels of Se dependent antioxidant enzymes (glutathione peroxidase and thioredoxin reductase) were evaluated to analyze the ROS neutralizing capacity of each Se-Y compound. The effects of Se-Y sources on Cd-induced DNA damage and apoptosis-associated DNA fragmentation was assessed using comet and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, respectively. Lesion-specific DNA damage analysis and in vitro DNA repair assay determined the DNA repair capacity of each Se-Y source. The results presented in this study confirm that the ability of different commercially available Se-Y preparations to enhance a range of cellular mechanisms that protect porcine gut epithelial cells from Cd-induced damage is concentration-dependent and illustrates the difference in bioefficiency of different Se-Y compounds.
Assuntos
Antioxidantes/farmacologia , Cádmio/toxicidade , Dano ao DNA , Células Epiteliais/efeitos dos fármacos , Jejuno/citologia , Substâncias Protetoras/farmacologia , Saccharomyces cerevisiae/química , Selênio/farmacologia , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Células Epiteliais/metabolismo , Oxirredução/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo , Relação Estrutura-Atividade , SuínosRESUMO
BACKGROUND: Response surface methodology (RSM) was used in a sequential manner to optimize solubilization and precipitation conditions in the recovery of protein from bovine lung using pH shift. RESULTS: Separate D-optimal designs were employed for protein solubilization and precipitation. Independent variables investigated for protein solubilization were time (10-120 min), temperature (4-20 °C), pH (8.0-11.0) and solvent/sample ratio (2.5-10). Variables for protein precipitation were time (0-60 min) and pH (4.25-6.00). Soluble protein yields ranged from 323 to 649 g kg-1 and the quadratic model for protein solubilization revealed a coefficient of determination R2 of 0.9958. Optimal conditions for maximum protein solubility were extraction time 140 min, temperature 19 °C, pH 10.8 and solvent/sample ratio 13.02. Protein precipitation yields varied from 407 to 667 g kg-1 , giving a coefficient of determination R2 of 0.9335. Optimal conditions for maximum protein precipitation were pH 5.03 and 60 min. Based on the RSM model, solubilization conditions were manipulated to maximize protein solubilization under reduced water and alkaline usage. These conditions were also validated. CONCLUSION: Models for solubilization and precipitation using bovine and porcine lung were validated; predicted and actual yields were in good agreement, showing cross-species applicability of the results. © 2017 Society of Chemical Industry.
Assuntos
Fracionamento Químico/métodos , Pulmão/química , Proteínas/isolamento & purificação , Animais , Bovinos , Concentração de Íons de Hidrogênio , Proteínas/análise , Solubilidade , TemperaturaRESUMO
Blood is generated in very large volumes as a by-product in slaughterhouses all around the world. On the one hand, blood generation presents a serious environmental issue because of its high pollutant capacity; however, on the other hand, blood has the potential to be collected and processed to generate high-added-value food ingredients based on its exceptional nutritive value and its excellent functional properties. In this paper, we review the current state of the art for blood processing, from collection to final recovery of protein isolates, the functional properties of blood, impact of processing on functional properties, and potential applications as food ingredients. Furthermore, future challenges are outlined for this underutilized and abundant product from the meat industry.
Assuntos
Ácido Cítrico/farmacologia , Anticoncepção , Ácido Láctico/farmacologia , Tartaratos/farmacologia , Anticoncepção/economia , Anticoncepção/métodos , Anticoncepcionais/farmacologia , Eficácia de Contraceptivos , Combinação de Medicamentos , Feminino , Humanos , Resultado do Tratamento , Cremes, Espumas e Géis Vaginais/farmacologiaRESUMO
PURPOSE: Ultramarathon running has gained popularity over several decades. Although there has been considerable research on training for other running events, from the 100-m to the marathon at 26.2 miles (42.2 km), there is little evidence on best practices for ultramarathons, where distances potentially exceed 100 miles (160.9 km). METHODS: In this case study, we examine the training regimen of an elite ultramarathon runner who broke 8 world records in 2021 and 2022, including the 24-hour run in which he ran 319.6 km in September 2022. Training data from December 28, 2020, to September 17, 2022, were collected from the Strava application database (recorded on Coros watch) and analyzed using Microsoft Excel and Tableau. RESULTS: Our subject completed 5 training blocks, with volume per training block averaging 172.1 to 263 km/wk. Peak running volume per training block occurred on average 3.2 weeks out from races and reached a maximum of 378 km/wk. Recovery was emphasized the week following a race, with less running (19 km/wk) and more cross-training. Interval-type workouts (1- to 10-km repeats) were completed throughout training blocks. The average pace during the 24-hour world-record run was 4 minutes and 30 seconds per kilometer (4:30/km), closely matching the overall average training pace. CONCLUSIONS: These findings suggest that training for ultramarathon races should include high-volume running at varied paces and intensity with cross-training to avoid injuries. We hope that this evidence helps athletes understand how to prepare for these ultraendurance events.
Assuntos
Resistência Física , Corrida , Masculino , Humanos , Corrida de Maratona , AtletasRESUMO
BACKGROUND: Callous-unemotional (CU) traits are characterized by low empathy, guilt, and prosociality, putting children at risk for lifespan antisocial behavior. Elevated CU traits have been linked separately to difficulties with emotion understanding (i.e., identifying emotional states of others) and disrupted parasympathetic nervous system (PNS) functioning. However, no study has investigated how PNS functioning and emotion understanding are jointly related to CU traits. METHOD: We explored associations between CU traits, emotion understanding, and PNS functioning (indexed via respiratory sinus arrhythmia [RSA]) among children aged 7-10 years old (n = 55). We also tested whether deficits in emotion understanding differ across specific emotions (i.e., fear, pain, happiness, anger). Each child's RSA was continuously recorded while they watched a film that included emotionally evocative social interactions. To assess emotion understanding, children identified emotions replayed in 1s animations of scenes from the film. Parents reported on child CU traits, conduct problems, and demographic information. RESULTS: Higher CU traits were related to lower emotion understanding (ß = -0.43, p = 0.03). PNS activity during the film moderated this association (ß = -0.47, p < 0.001), such that CU traits were associated with lower emotion understanding among children with mean (B = -0.01, t = -2.46, p = 0.02) or high (i.e., 1 SD > M; B = -0.02, t = -3.00, p < 0.001) RSA levels during the film, but not among children with low RSA levels (i.e., 1 SD < M; B = 0.00, t = -0.53, p = 0.60). Moreover, we found that the observed moderated associations are driven by deficits in fear, specifically. CONCLUSIONS: The link between poorer emotion understanding, fear understanding in particular, and CU traits was attenuated for children who demonstrated patterns of PNS functioning consistent with attentional engagement while viewing the emotion stimuli.
RESUMO
Chimeric RNAs, distinct from DNA gene fusions, have emerged as promising therapeutic targets with diverse functions in cancer treatment. However, the functional significance and therapeutic potential of most chimeric RNAs remain unclear. Here we identify a novel fusion transcript of solute carrier family 2-member 11 (SLC2A11) and macrophage migration inhibitory factor (MIF). In this study, we investigated the upregulation of SLC2A11-MIF in The Cancer Genome Atlas cohort and a cohort of patients from Sun Yat-Sen Memorial Hospital. Subsequently, functional investigations demonstrated that SLC2A11-MIF enhanced the proliferation, antiapoptotic effects, and metastasis of bladder cancer cells in vitro and in vivo. Mechanistically, the fusion protein encoded by SLC2A11-MIF interacted with polypyrimidine tract binding protein 1 (PTBP1) and regulated the mRNA half-lives of Polo Like Kinase 1, Roundabout guidance receptor 1, and phosphoinositide-3-kinase regulatory subunit 3 in BCa cells. Moreover, PTBP1 knockdown abolished the enhanced impact of SLC2A11-MIF on biological function and mRNA stability. Furthermore, the expression of SLC2A11-MIF mRNA is regulated by CCCTC-binding factor and stabilized through RNA N4-acetylcytidine modification facilitated by N-acetyltransferase 10. Overall, our findings revealed a significant fusion protein orchestrated by the SLC2A11-MIF-PTBP1 axis that governs mRNA stability during the multistep progression of bladder cancer.
RESUMO
This study describes the first long-term (14-year) evaluation of the efficacy of an established (>100 years) natural wetland to remediate highly acidic mine drainage (AMD). Although natural wetlands are highly valued for their biodiversity, this study demonstrates that they also provide important ecosystem service functions through their ability to consistently and reliably improve water quality by mitigating AMD. The Afon Goch river flows from Parys Mountain copper mine via a natural wetland, and was the major source of Zn and Cu contamination to the Irish Sea. Prior to 2003 the wetland received severe acidic metal contamination and retained a large proportion of the contamination (55, 64, and 37% in dissolved Fe, Zn, and Cu) leading to a greatly reduced metal flow to the Irish Sea. Reduced wetland loadings midway through the sampling period led to a reduction of metals by 83-94% and a pH increase from 2.7 to 5.5, resulting in long-term improvements in the downstream benthic invertebrate community. High root metal accumulation by the dominant wetland plant species and the association of acidophilic bacteria in the wetland rhizosphere indicate that multiple interacting processes provide an efficient and self-sustaining system to remediate AMD.