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Nucleoli are multicomponent condensates defined by coexisting sub-phases. We identified distinct intrinsically disordered regions (IDRs), including acidic (D/E) tracts and K-blocks interspersed by E-rich regions, as defining features of nucleolar proteins. We show that the localization preferences of nucleolar proteins are determined by their IDRs and the types of RNA or DNA binding domains they encompass. In vitro reconstitutions and studies in cells showed how condensation, which combines binding and complex coacervation of nucleolar components, contributes to nucleolar organization. D/E tracts of nucleolar proteins contribute to lowering the pH of co-condensates formed with nucleolar RNAs in vitro. In cells, this sets up a pH gradient between nucleoli and the nucleoplasm. By contrast, juxta-nucleolar bodies, which have different macromolecular compositions, featuring protein IDRs with very different charge profiles, have pH values that are equivalent to or higher than the nucleoplasm. Our findings show that distinct compositional specificities generate distinct physicochemical properties for condensates.
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Nucléolo Celular , Proteínas Nucleares , Força Próton-Motriz , Nucléolo Celular/química , Núcleo Celular/química , Proteínas Nucleares/química , RNA/metabolismo , Separação de Fases , Proteínas Intrinsicamente Desordenadas/química , Animais , Xenopus laevis , Oócitos/química , Oócitos/citologiaRESUMO
Mitotic spindles are composed of microtubules (MTs) that must nucleate at the right place and time. Ran regulates this process by directly controlling the release of spindle assembly factors (SAFs) from nucleocytoplasmic shuttle proteins importin-αß and subsequently forms a biochemical gradient of SAFs localized around chromosomes. The majority of spindle MTs are generated by branching MT nucleation, which has been shown to require an eight-subunit protein complex known as augmin. In Xenopus laevis, Ran can control branching through a canonical SAF, TPX2, which is nonessential in Drosophila melanogaster embryos and HeLa cells. Thus, how Ran regulates branching MT nucleation when TPX2 is not required remains unknown. Here, we use in vitro pulldowns and total internal reflection fluorescence microscopy to show that augmin is a Ran-regulated SAF. We demonstrate that augmin directly interacts with both importin-α and importin-ß through two nuclear localization sequences on the Haus8 subunit, which overlap with the MT-binding site. Moreover, we show that Ran controls localization of augmin to MTs in both Xenopus egg extract and in vitro. Our results demonstrate that RanGTP directly regulates augmin, which establishes a new way by which Ran controls branching MT nucleation and spindle assembly both in the absence and presence of TPX2.
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Proteínas Associadas aos Microtúbulos , Complexos Multiproteicos , Proteínas de Xenopus , Proteína ran de Ligação ao GTP , Animais , Humanos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Drosophila melanogaster , Células HeLa , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Microtúbulos/metabolismo , Proteína ran de Ligação ao GTP/genética , Proteína ran de Ligação ao GTP/metabolismo , Fuso Acromático/metabolismo , Xenopus laevis/metabolismo , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo , Complexos Multiproteicos/genética , Complexos Multiproteicos/metabolismo , alfa Carioferinas , beta CarioferinasRESUMO
OBJECTIVE: The aim of this systematic review and meta-analysis is to describe the effect of digitally delivered exercise on pain, physical function and quality of life (QoL) for people with knee or hip osteoarthritis (OA). METHODS: Articles were eligible for inclusion if they were of a randomized control trial that evaluated the prescription of digitally delivered exercise (requiring the internet) in people with symptomatic primary hip and/or knee OA. Risk of bias was assessed using the Physiotherapy Evidence Database scale, and levels of evidence were assessed according to Grading of Recommendations Assessment, Development and Evaluation. RESULTS: Digitally delivered exercise was delivered via synchronous and asynchronous methods (or a combination of both). Digitally delivered exercise was superior to education only for pain and physical function, with high-quality evidence for quality-of-life outcomes in the long-term (standardized mean difference -0.35, 95% confidence interval -0.59 to -0.12, P = 0.003) in people with knee OA. Furthermore, there was very low to low-quality evidence that digitally delivered exercise was comparable to face-to-face delivery in the short and long-term for people with hip or knee OA and comparable in the medium-term for people with knee OA only. DISCUSSION: The review demonstrated very low to low-quality evidence that digitally delivered exercise was comparable to face-to-face delivery for pain, function and QoL. In the absence of higher-level evidence, we would provisionally recommend that healthcare providers offer the choice of face-to-face or digitally delivered exercise intervention for people with hip or knee OA. Further work is required to understand these programs' reach, access, uptake and implementation across diverse population groups.
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Osteoartrite do Quadril , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/terapia , Osteoartrite do Quadril/terapia , Qualidade de Vida , Terapia por Exercício/métodos , Dor , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Back pain is a huge global problem. For some people, the pain is so severe that they feel the need to present to an emergency department (ED). Our aim was to explore patient and staff perspectives for the development of a digital care pathway (DCP) for people with back pain who have presented to ED, including acceptability, barriers and facilitators. METHODS: We used a descriptive phenomenology approach using semi-structured interviews with patient and staff participants at a tertiary hospital. Interviews were transcribed and data codes were developed using inductive thematic analysis. Themes were discussed between researchers until consensus was achieved. RESULTS: A total of 16 interviews were carried out, half of which involved patient participants. We identified three major themes: (i) expectations and experiences of staff and patients with low back pain in ED; (ii) a digital care pathway can empower patients and support clinicians in providing care; and (iii) acceptability, barriers, facilitators and recommendations of engaging with a DCP to track the trajectory of back pain. Each theme was further categorised into subthemes. CONCLUSION: Introducing a DCP was perceived as acceptable and beneficial by patients and staff. Both groups were aware of the potential participant burden if surveys were too long. Introducing a DCP could be a valuable adjunct to current management care models, providing a standardised source of education with the potential for individualised tracking and monitoring. The design and development of a DCP will need to consider reported facilitators and address perceived barriers for engagement. PATIENT OR PUBLIC CONTRIBUTION: This project sought insights from patients and staff about a digital care pathway. This forms the first step of patient and consumer consultation before implementing a digital care pathway. All consumers were offered the opportunity to review their responses and our interpretation.
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Serviço Hospitalar de Emergência , Entrevistas como Assunto , Dor Lombar , Pesquisa Qualitativa , Humanos , Dor Lombar/terapia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Procedimentos Clínicos , Atitude do Pessoal de Saúde , IdosoRESUMO
Ankle arthrodesis and total ankle arthroplasty are both well-accepted surgical treatment options for end-stage ankle arthrosis. However, total ankle arthroplasty has gained popularity as the survivability of implants is improving. It is understood that there is loss of bone height following tibiotalocalcaneal arthrodesis, but to our knowledge, this has not been investigated in the setting of total ankle arthroplasty. A retrospective radiographic review was conducted over a 5-year period. We investigated all patients who underwent a tibiotalocalcaneal arthrodesis or total ankle arthroplasty for treatment of ankle arthritis by a single fellowship-trained orthopedic surgeon. The anterior and posterior height measurements were measured on preoperative and postoperative lateral radiographs. Differences between preoperative and postoperative heights were analyzed through a series of analyses of covariance. One hundred and thirty-three patients and 143 operative extremities were included: 71 operative extremities in the tibiotalocalcaneal arthrodesis group (mean age 55.5 ± 13.3 years, BMI 32.2 ± 7.9) and 72 in the total ankle arthroplasty group (mean age 65.4 ± 9.5 years, BMI 30.7 ± 6.4). Statistical analysis demonstrated a loss of height in the tibiotalocalcaneal arthrodesis group, and an increased anterior and posterior height in the total ankle arthroplasty group. However, when comparing the arthroplasty group and arthrodesis group only the anterior height measurement reached statistical significance when stratified by gender (p < .001). The potential change in height is an important factor to consider during surgical planning as a limb length discrepancy may result.
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Artroplastia de Substituição do Tornozelo , Osteoartrite , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Tornozelo/cirurgia , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/cirurgia , Estudos Retrospectivos , Artroplastia de Substituição do Tornozelo/efeitos adversos , Osteoartrite/diagnóstico por imagem , Osteoartrite/cirurgia , Artrodese , Resultado do TratamentoRESUMO
OBJECTIVES: Back pain is a prevalent condition that affects 1 in 6 Australians at any time, with high associated health care costs. To date, there is limited information relating to symptom severity and recovery trajectory in people with back pain who present to the emergency department for care. A digital care pathway (DCP) can track patient outcomes following presentation with back pain. The primary aim of this protocol is to outline the co-development, implementation, and evaluation of a DCP for back pain patients who present to the emergency department. METHODS: The primary aim will be addressed in 3 overlapping phases: Phase 1 (co-design) will include interviews with back pain patients and health care professionals from the Northern Hospital Emergency Department. Interview findings will inform education resources featured on the DCP and establish questionnaire content and frequency acceptability. Phase 2 (implementation) will include the rollout of the DCP and tracking of patient-reported outcome measures, which will be collected over 12 weeks. Phase 3 (evaluation) will include interviews with a subset of back pain patients who have participated in Phase 2 to evaluate the acceptability of the DCP and the barriers and facilitators of using the DCP. ETHICS AND DISSEMINATION: This project has been approved via the National Health and Medical Research Council of Australia's National Mutual Acceptance Scheme by St Vincent's Hospital Human Ethics Committee (2022/PID06476), La Trobe University Research Governance (HEC#206/22), and Northern Health Research Governance (NH-2023-372687). We plan to publish the findings in a peer-reviewed journal and present them at conferences.
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The aim of this study was to examine the possession (very low, low, high, and very high), team formation (3-5-2 and 4-3-3) and position (centre-backs, full-backs, centre midfielders, attacking midfielders, and centre forwards) on match load across two consecutive seasons in elite soccer. Twenty-seven English Premier League outfield players were recruited. Data was monitored through an 18 Hz Global Positioning System and a 25 Hz semi-automated camera tracking system, respectively, and all variables were analysed per minute. Main effects for formation on total distance (TD) (p = 0.006; η 2 = 0.010), high-speed running (HSR) (p = 0.009; η 2 = 0.009), number of high metabolic load (HML) efforts (p = 0.004; η 2 = 0.011) were observed. In addition, there were significant interaction effects with formation × possession on TD (p < 0.001; η 2 = 0.043), HSR (p = 0.006; η 2 = 0.018), sprinting (p < 0.001; η 2 = 0.030), HML efforts (p < 0.001; η 2 = 0.035), accelerations (p < 0.001; η 2 = 0.025). From the position-specific analysis, only the running performance of centre-backs was affected by formation or positional factors. These results indicate that formation and possession can have a significant impact on TD, HSR, and HML distance. Furthermore, players performed more high-intensity efforts in 3-5-2 than 4-3-3 formation. These findings suggest that coaches can evaluate running performance in the context of formation and possession and tailor tactical strategies to optimise physical performance.
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Tendons and ligaments are crucial components of the musculoskeletal system, yet the pathways specifying these fates remain poorly defined. Through a screen of known bioactive chemicals in zebrafish, we identified a new pathway regulating tendon cell induction. We established that statin, through inhibition of the mevalonate pathway, causes an expansion of the tendon progenitor population. Co-expression and live imaging studies indicate that the expansion does not involve an increase in cell proliferation, but rather results from re-specification of cells from the neural crest-derived sox9a+/sox10+ skeletal lineage. The effect on tendon cell expansion is specific to the geranylgeranylation branch of the mevalonate pathway and is mediated by inhibition of Rac activity. This work establishes a novel role for the mevalonate pathway and Rac activity in regulating specification of the tendon lineage.
Assuntos
Ácido Mevalônico/metabolismo , Tendões/metabolismo , Alquil e Aril Transferases/antagonistas & inibidores , Alquil e Aril Transferases/genética , Alquil e Aril Transferases/metabolismo , Animais , Animais Geneticamente Modificados/metabolismo , Atorvastatina/farmacologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Farnesiltranstransferase/antagonistas & inibidores , Farnesiltranstransferase/genética , Farnesiltranstransferase/metabolismo , Morfolinos/metabolismo , Crista Neural/metabolismo , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Fatores de Transcrição SOXE/genética , Fatores de Transcrição SOXE/metabolismo , Transdução de Sinais , Células-Tronco/citologia , Células-Tronco/metabolismo , Tendões/citologia , Tendões/patologia , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/antagonistas & inibidores , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Proteínas rac de Ligação ao GTP/antagonistas & inibidores , Proteínas rac de Ligação ao GTP/metabolismoRESUMO
The domesticated sunflower, Helianthus annuus L., is a global oil crop that has promise for climate change adaptation, because it can maintain stable yields across a wide variety of environmental conditions, including drought. Even greater resilience is achievable through the mining of resistance alleles from compatible wild sunflower relatives, including numerous extremophile species. Here we report a high-quality reference for the sunflower genome (3.6 gigabases), together with extensive transcriptomic data from vegetative and floral organs. The genome mostly consists of highly similar, related sequences and required single-molecule real-time sequencing technologies for successful assembly. Genome analyses enabled the reconstruction of the evolutionary history of the Asterids, further establishing the existence of a whole-genome triplication at the base of the Asterids II clade and a sunflower-specific whole-genome duplication around 29 million years ago. An integrative approach combining quantitative genetics, expression and diversity data permitted development of comprehensive gene networks for two major breeding traits, flowering time and oil metabolism, and revealed new candidate genes in these networks. We found that the genomic architecture of flowering time has been shaped by the most recent whole-genome duplication, which suggests that ancient paralogues can remain in the same regulatory networks for dozens of millions of years. This genome represents a cornerstone for future research programs aiming to exploit genetic diversity to improve biotic and abiotic stress resistance and oil production, while also considering agricultural constraints and human nutritional needs.
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Evolução Molecular , Flores/genética , Flores/fisiologia , Genoma de Planta/genética , Helianthus/genética , Helianthus/metabolismo , Óleos de Plantas/metabolismo , Aclimatação/genética , Duplicação Gênica/genética , Regulação da Expressão Gênica de Plantas , Variação Genética , Genômica , Helianthus/classificação , Análise de Sequência de DNA , Estresse Fisiológico/genética , Óleo de Girassol , Transcriptoma/genéticaRESUMO
OBJECTIVE: To determine if laser speckle contrast imaging (LSCI) mitigates variations and subjectivity in the use and interpretation of indocyanine green (ICG) fluorescence in the current visualization paradigm of real-time intraoperative tissue blood flow/perfusion in clinically relevant scenarios. METHODS: De novo laparoscopic imaging form-factor detecting real-time blood flow using LSCI and blood volume by near-infrared fluorescence (NIRF) of ICG was compared to ICG NIRF alone, for dye-less real-time visualization of tissue blood flow/perfusion. Experienced surgeons examined LSCI and ICG in segmentally devascularized intestine, partial gastrectomy, and the renal hilum across six porcine models. Precision and accuracy of identifying demarcating lines of ischemia/perfusion in tissues were determined in blinded subjects with varying levels of surgical experience. RESULTS: Unlike ICG, LSCI perfusion detection was real time (latency < 150 ms: p < 0.01), repeatable and on-demand without fluorophore injection. Operating surgeons (n = 6) precisely and accurately identified concordant demarcating lines in white light, LSCI, and ICG modes immediately. Blinded subjects (n = 21) demonstrated similar spatial-temporal precision and accuracy with all three modes ≤ 2 min after ICG injection, and discordance in ICG mode at ≥ 5 min in devascularized small intestine (p < 0.0001) and in partial gastrectomy (p < 0.0001). CONCLUSIONS: Combining LSCI for near real-time blood flow detection with ICG fluorescence for blood volume detection significantly improves precision and accuracy of perfusion detection in tissue locations over time, in real time, and repeatably on-demand than ICG alone.
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Verde de Indocianina , Laparoscopia , Animais , Suínos , Imagem de Contraste de Manchas a Laser , Estudos de Viabilidade , Laparoscopia/métodos , PerfusãoRESUMO
The mechanisms underlying a tendency among individuals with depression to report personal episodic memories with low specificity remain to be understood. We assessed a sample of undergraduate students with dysphoria to determine whether depression relates to a broader dysregulation of balancing accuracy and informativeness during memory reports. Specifically, we investigated metamnemonic processes using a quantity-accuracy profile approach. Recall involved three phases with increasing allowance for more general, or coarse-grained, responses: (a) forced-precise responding, requiring high precision; (b) free-choice report with high and low penalty incentives on accuracy; (c) a lexical description phase. Individuals with and without dysphoria were largely indistinguishable across indices of retrieval, monitoring, and control aspects of metamemory. The results indicate intact metacognitive processing in young individuals with dysphoria and provide no support for the view that impaired metacognitive control underlies either memory deficits or bias in memory reports that accompany dysphoria.
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Transtorno Depressivo Maior , Memória Episódica , Metacognição , Humanos , Rememoração Mental/fisiologia , Metacognição/fisiologia , Transtornos da MemóriaRESUMO
OBJECTIVE: Investigate sex/gender differences in self-reported activity and knee-related outcomes after anterior cruciate ligament (ACL) injury. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Seven databases were searched in December 2021. ELIGIBILITY CRITERIA: Observational or interventional studies with self-reported activity (including return to sport) or knee-related outcomes after ACL injury. RESULTS: We included 242 studies (n=123 687, 43% females/women/girls, mean age 26 years at surgery). One hundred and six studies contributed to 1 of 35 meta-analyses (n=59 552). After ACL injury/reconstruction, very low-certainty evidence suggests females/women/girls had inferior self-reported activity (ie, return to sport, Tegner Activity Score, Marx Activity Scale) compared with males/men/boys on most (88%, 7/8) meta-analyses. Females/women/girls had 23%-25% reduced odds of returning to sport within 1-year post-ACL injury/reconstruction (12 studies, OR 0.76 95% CI 0.63 to 0.92), 1-5 years (45 studies, OR 0.75 95% CI 0.69 to 0.82) and 5-10 years (9 studies, OR 0.77 95% CI 0.57 to 1.04). Age-stratified analysis (<19 years) suggests female athletes/girls had 32% reduced odds of returning to sport compared with male athletes/boys (OR 0.68, 95% CI 0.41 to 1.13, I2 0.0%). Very low-certainty evidence suggests females/women/girls experienced inferior knee-related outcomes (eg, function, quality of life) on many (70%, 19/27) meta-analyses: standardised mean difference ranging from -0.02 (Knee injury and Osteoarthritis Outcome Score, KOOS-activities of daily living, 9 studies, 95% CI -0.05 to 0.02) to -0.31 (KOOS-sport and recreation, 7 studies, 95% CI -0.36 to -0.26). CONCLUSIONS: Very low-certainty evidence suggests inferior self-reported activity and knee-related outcomes for females/women/girls compared with males/men/boys after an ACL injury. Future studies should explore factors and design targeted interventions to improve outcomes for females/women/girls. PROSPERO REGISTRATION NUMBER: CRD42021205998.
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Lesões do Ligamento Cruzado Anterior , Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Lesões do Ligamento Cruzado Anterior/cirurgia , Autorrelato , Qualidade de Vida , Atividades Cotidianas , Articulação do Joelho/cirurgia , Volta ao EsporteRESUMO
Previous research has shown that /l/ in Spanish displays patterns of articulatory variability that are determined by a complex interaction of phonetic, phonological and dialectal factors. In this study, we report the results of an experiment using Ultrasound Tongue Imaging (UTI) that tests /l/-articulations in a dialectal cross-section of Spanish speakers. We show that lengthening of /l/ in phrase-edge contexts is accompanied by articulatory distinctions (e.g. root/dorsum retraction) for some speakers, whereas others produce lengthened realisations of /l/ in these contexts without observable differences in tongue position. We also find acoustic evidence for reduction in utterance-medial intervocalic and preconsonantal environments (duration, intensity, F1 frequency measures are discussed). However, articulatory correlates of reduction are not consistently observed across speakers in these contexts. As well as relating the results to prosodically-driven strengthening and reduction patterns, our findings are of relevance to debates about resyllabification in Spanish. Specifically, we argue that our results cannot be straightforwardly accommodated under phonological analysis assuming that word-final consonants regularly resyllabify across word boundaries prevocalically.
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Idioma , Fonética , Humanos , Acústica da Fala , Acústica , Língua/diagnóstico por imagemRESUMO
Tibiotalocalcaneal arthrodesis (TTCA) with an intramedullary rod is a viable treatment option for a myriad of pathologies involving the foot and ankle. While the current literature has focused on fixation techniques, deformity correction, and clinical outcomes, we are unaware of any studies specifically examining change in height following a TTCA. In the present study, we retrospectively analyzed radiographs with novel radiographic techniques to determine the change in height from preoperative to postoperative radiographs following TTCA. Patients were divided into 3 categories: Charcot, arthritis, and pes planus as the indication for surgical intervention. We found that Charcot and arthritis had an average decrease in height on anterior and posterior measurements of the height from the distal tibia to the calcaneus, while pes planus had an increase in height. The average Charcot change in height was -12.0 ± 24.4 mm anteriorly and -7.6 ± 15.5 mm posteriorly. The average change in height for the arthritis group was -6.9 ± 6.7 mm anteriorly and -3.8 ± 5.8 mm posteriorly. The pes planus group was found to have an average increase in height 0.5 ± 8.0 mm anteriorly and 2.9 ± 5.8 mm posteriorly. Overall, we found a statistically significant difference in height change between the 3 groups in anterior measurements (p = .012) and posterior measurement (p = .006). We recommend surgeons who perform this procedure to be aware of the potential change in height to better tailor surgical and postoperative care.
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Artrite , Pé Chato , Humanos , Estudos Retrospectivos , Artrite/diagnóstico por imagem , Artrite/cirurgia , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/cirurgia , Artrodese/métodos , Pinos OrtopédicosRESUMO
The microtubule-based mitotic spindle is responsible for equally partitioning the genome during each cell division, and its assembly is executed via several microtubule nucleation pathways. Targeting Protein for XKlp2 (TPX2) stimulates the branching microtubule nucleation pathway, where new microtubules are nucleated from preexisting ones within mitotic or meiotic spindles. TPX2, like other spindle assembly factors, is sequestered by binding to nuclear importins-α/ß until the onset of mitosis, yet the molecular nature of this regulation remains unclear. Here we demonstrate that TPX2 interacts with importins-α/ß with nanomolar affinity in a 1:1:1 monodispersed trimer. We also identify a new nuclear localization sequence in TPX2 that contributes to its high-affinity interaction with importin-α. In addition, we establish that TPX2 interacts with importin-ß via dispersed, weak interactions. We show that interactions of both importin-α and -ß with TPX2 inhibit its ability to undergo phase separation, which was recently shown to enhance the kinetics of branching microtubule nucleation. In summary, our study informs how importins regulate TPX2 to facilitate spindle assembly, and provides novel insight into the functional regulation of protein phase separation.
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Proteínas de Ciclo Celular/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Fuso Acromático/metabolismo , alfa Carioferinas/metabolismo , beta Carioferinas/metabolismo , Cromatografia em Gel/métodos , Humanos , Microtúbulos/metabolismo , Sinais de Localização Nuclear , Proteínas Nucleares/metabolismo , Ligação ProteicaRESUMO
A population's spatial structure affects the rate of genetic change and the outcome of natural selection. These effects can be modeled mathematically using the Birth-death process on graphs. Individuals occupy the vertices of a weighted graph, and reproduce into neighboring vertices based on fitness. A key quantity is the probability that a mutant type will sweep to fixation, as a function of the mutant's fitness. Graphs that increase the fixation probability of beneficial mutations, and decrease that of deleterious mutations, are said to amplify selection. However, fixation probabilities are difficult to compute for an arbitrary graph. Here we derive an expression for the fixation probability, of a weakly-selected mutation, in terms of the time for two lineages to coalesce. This expression enables weak-selection fixation probabilities to be computed, for an arbitrary weighted graph, in polynomial time. Applying this method, we explore the range of possible effects of graph structure on natural selection, genetic drift, and the balance between the two. Using exhaustive analysis of small graphs and a genetic search algorithm, we identify families of graphs with striking effects on fixation probability, and we analyze these families mathematically. Our work reveals the nuanced effects of graph structure on natural selection and neutral drift. In particular, we show how these notions depend critically on the process by which mutations arise.
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Deriva Genética , Modelos Genéticos , Neoplasias/patologia , Probabilidade , Seleção Genética , Algoritmos , Evolução Biológica , Simulação por Computador , Humanos , Matemática , Mutação , Dinâmica Populacional , TemperaturaRESUMO
Cam morphology size and location might affect the severity of reported burden in people with femoroacetabular impingement (FAI) syndrome. We investigated the relationship between cam morphology size (i.e., alpha angle) and self-reported hip/groin burden (i.e., scores for the International Hip Outcome Tool-33 (iHOT-33) and Copenhagen Hip and Groin Outcome Score (HAGOS)), examined separately for the anteroposterior pelvis (AP) and Dunn 45° radiographs in football players with FAI syndrome. In total, 118 (12 women) subelite football (soccer or Australian football) players with FAI syndrome with cam morphology (alpha angle ≥60°) participated. One blinded assessor quantified superior and anterosuperior cam morphology size by measuring alpha angles for the AP and Dunn 45° radiographs, respectively. Linear regression models investigated relationships between alpha angle (continuous independent variable, separately measured for the AP and Dunn 45° radiographs) and iHOT-33 and HAGOS scores (dependent variables). Larger anterosuperior cam morphology (seen on the Dunn 45° radiograph) was associated with lower (i.e., worse) scores for the iHOT-Total, iHOT-Symptoms, iHOT-Job, and iHOT-Social subscales (unadjusted estimate range -0.553 to -0.319 [95% confidence interval -0.900 to -0.037], p = 0.002 to 0.027), but not the iHOT-Sport (p = 0.459) nor any HAGOS scores (p = 0.110 to 0.802). Superior cam morphology size (measured using the AP radiograph) was not associated with any iHOT-33 or HAGOS scores (p = 0.085 to 0.975). Larger anterosuperior cam morphology may be more relevant to pain and symptoms in football players with FAI syndrome than superior cam morphology, warranting investigation of its effects on reported burden and hip disease over time.
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Impacto Femoroacetabular , Futebol , Esportes de Equipe , Feminino , Humanos , Austrália , Impacto Femoroacetabular/diagnóstico por imagem , Articulação do Quadril , AutorrelatoRESUMO
BACKGROUND: The incidence of anterior cruciate ligament (ACL) injuries represents a large burden of knee injuries in both the general and sporting populations, often requiring surgical intervention. Although there is much research on complete ACL tears including outcomes and indications for surgery, little is known about the short- and long-term outcomes of non-operative, physiotherapy led intervention in partial ACL tears. The primary aim of this study was to evaluate studies looking at the effectiveness of physiotherapy led interventions in improving pain and function in young and middle-aged adults with partial ACL tears. Additionally, the secondary aim was to evaluate the completeness of exercise prescription in randomised trials for physiotherapy led interventions in the management in partial ACL tears. METHODS: A comprehensive and systematic search was performed on six databases (Medline, CINAHL, EMBASE, PEDro, Scopus, SPORTDiscus and Cochrane). The search strategy consisted of two main concepts: (i) partial ACL tears, and (ii) non-operative management. 7,587 papers were identified by the search. After screening of eligible articles by two independent reviewers, 2 randomised studies were included for analysis. The same two reviewers assessed the completeness of reporting using the Toigio and Boutellier mechanobiological exercise descriptions and Template for Intervention Description and Replication (TIDieR) checklist. Group mean standard deviations (SD) for the main outcomes was extracted from both papers for analysis. Prospero Registration Number: CRD42020179892. RESULTS: The search strategy identified two studies; one looking at Tai Chi and the other Pilates. The analysis indicated that Tai Chi was significant in reducing pain scores and both Tai Chi and Pilates were found to increase Muscle Peak Torque Strength (MPTS) at 180 degrees. Furthermore, Tai Chi showed a significant increase in proprioception. CONCLUSIONS: Physiotherapy led interventions such as Pilates, and Tai Chi may improve pain, proprioception and strength in young and middle-aged adults with partial ACL tears, however full scale, high-quality randomised studies are required with long term outcomes recorded.
Assuntos
Lesões do Ligamento Cruzado Anterior/terapia , Reconstrução do Ligamento Cruzado Anterior , Modalidades de Fisioterapia , Adulto , Lesões do Ligamento Cruzado Anterior/complicações , Lesões do Ligamento Cruzado Anterior/epidemiologia , Lesões do Ligamento Cruzado Anterior/cirurgia , Técnicas de Exercício e de Movimento/métodos , Técnicas de Exercício e de Movimento/normas , Humanos , Pessoa de Meia-Idade , Dor/cirurgia , Modalidades de Fisioterapia/normas , Propriocepção , Ensaios Clínicos Controlados Aleatórios como Assunto , Tai Chi Chuan/métodos , Tai Chi Chuan/normas , Resultado do TratamentoRESUMO
OBJECTIVE: To systematically review and synthesise patellofemoral joint reaction force (PFJRF) in healthy individuals and those with patellofemoral pain and osteoarthritis (OA), during everyday activities, therapeutic exercises and with physical interventions (eg, foot orthotics, footwear, taping, bracing). DESIGN: A systematic review with meta-analysis. DATA SOURCES: Medline, Embase, Scopus, CINAHL, SportDiscus and Cochrane Library databases were searched. ELIGIBILITY CRITERIA: Observational and interventional studies reporting PFJRF during everyday activities, therapeutic exercises, and physical interventions. RESULTS: In healthy individuals, the weighted average of mean (±SD) peak PFJRF for everyday activities were: walking 0.9±0.4 body weight (BW), stair ascent 3.2±0.7 BW, stair descent 2.8±0.5 BW and running 5.2±1.2 BW. In those with patellofemoral pain, peak PFJRF were: walking 0.8±0.2 BW, stair ascent 2.5±0.5 BW, stair descent 2.6±0.5 BW, running 4.1±0.9 BW. Only single studies reported peak PFJRF during everyday activities in individuals with patellofemoral OA/articular cartilage defects (walking 1.3±0.5 BW, stair ascent 1.6±0.4 BW, stair descent 1.0±0.5 BW). The PFJRF was reported for many different exercises and physical interventions; however, considerable variability precluded any pooled estimates. SUMMARY: Everyday activities and exercises involving larger knee flexion (eg, squatting) expose the patellofemoral joint to higher PFJRF than those involving smaller knee flexion (eg, walking). There were no discernable differences in peak PFJRF during everyday activities between healthy individuals and those with patellofemoral pain/OA. The information on PFJRF may be used to select appropriate variations of exercises and physical interventions.
Assuntos
Articulação Patelofemoral , Síndrome da Dor Patelofemoral , Fenômenos Biomecânicos , Humanos , Articulação do Joelho , Postura , CaminhadaRESUMO
Background: The development of healthy relationships and connections is of fundamental importance to adolescent well-being. The use of social media plays a vital role in the lives of young Canadians, yet the association between different types of social media use and the quality of relationships and connections remains unknown, and most existing analyses on this topic are based on modest and non-representative samples. Data and methods: Using 2017/2018 reports from the nationally representative Health Behaviour in School-aged Children study (n=17,149; ages 11 to 15 years), the strength, consistency and significance of associations was examined between intensive (frequent use to connect with other people) and problematic (use that depicts addictive qualities) social media use and available measures of adolescent relationships and connections. Results: Overall, intensive use (online communication with others almost all of the time) and problematic use (potential addiction to social media) were more common in girls than boys (38% of girls versus 30% of boys and 7.7% of girls versus 5.2% of boys, respectively), with prevalence levels that rose with age. Intensive use was associated with more positive social relationships with friends, especially among girls (relative risk [RR] = 1.40 [95% confidence interval (CI) 1.28 - 1.54]), while problematic use was consistently and negatively associated with strong relationships and connections in all groups in the study. Notably, problematic use was negatively associated with strong family relationships in boys (RR = 0.58 [95% CI 0.42 to 0.79]) and girls (RR=0.48 [95% CI 0.36 to 0.63]). Interpretation: Intensive use of social media has the potential to strengthen relationships and connections in adolescents. However, when social media use becomes addictive or "problematic", it is highly correlated with weaker relationships and a sense of social disconnection. Public health initiatives related to social media use should consider how different types of social media use have the potential to impact on different aspects of health.