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1.
Acad Med ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38722282

RESUMO

ABSTRACT: Most medical schools have instituted undergraduate medical education (UME) well-being programs in recent years in response to high rates of medical student distress, but there is currently significant variability in the structure of UME well-being programs and limited guidance on how to best structure such programs to achieve success. In this article, the authors, all leaders of medical student well-being programs at their home institutions and members of the Association of American Medical Colleges Group on Student Affairs Committee on Student Affairs Working Group on Medical Student Well-Being between 2019 and 2023, offer guidance to the national community on how best to structure a UME well-being program. They use the current literature and their professional experiences leading well-being efforts at 7 different institutions to review the case for addressing medical student well-being, propose a guiding model, and make recommendations for strategies to implement this model.The proposed guiding model emphasizes the importance of the learning environment and efficiency of learning to medical student well-being, as well as personal resilience. Based on this model, the authors recommend specific and tangible well-being strategies to implement systemic interventions to improve the learning environment, efficiency of learning, and personal resilience, including: formalizing the well-being program; hiring qualified, dedicated, and empowered well-being leadership with clear responsibilities; acting as a central hub for resources and as a liaison with mental health care; and establishing robust program evaluation methods.

2.
Mol Ecol ; 33(11): e17353, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38613250

RESUMO

Effective population size (Ne) is a particularly useful metric for conservation as it affects genetic drift, inbreeding and adaptive potential within populations. Current guidelines recommend a minimum Ne of 50 and 500 to avoid short-term inbreeding and to preserve long-term adaptive potential respectively. However, the extent to which wild populations reach these thresholds globally has not been investigated, nor has the relationship between Ne and human activities. Through a quantitative review, we generated a dataset with 4610 georeferenced Ne estimates from 3829 populations, extracted from 723 articles. These data show that certain taxonomic groups are less likely to meet 50/500 thresholds and are disproportionately impacted by human activities; plant, mammal and amphibian populations had a <54% probability of reaching N ̂ e = 50 and a <9% probability of reaching N ̂ e = 500. Populations listed as being of conservation concern according to the IUCN Red List had a smaller median N ̂ e than unlisted populations, and this was consistent across all taxonomic groups. N ̂ e was reduced in areas with a greater Global Human Footprint, especially for amphibians, birds and mammals, however relationships varied between taxa. We also highlight several considerations for future works, including the role that gene flow and subpopulation structure plays in the estimation of N ̂ e in wild populations, and the need for finer-scale taxonomic analyses. Our findings provide guidance for more specific thresholds based on Ne and help prioritise assessment of populations from taxa most at risk of failing to meet conservation thresholds.


Assuntos
Anfíbios , Conservação dos Recursos Naturais , Genética Populacional , Mamíferos , Densidade Demográfica , Animais , Anfíbios/genética , Anfíbios/classificação , Mamíferos/genética , Mamíferos/classificação , Fluxo Gênico , Aves/genética , Aves/classificação , Humanos , Endogamia , Deriva Genética , Plantas/genética , Plantas/classificação , Atividades Humanas
3.
J Surg Res ; 297: 83-87, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38460453

RESUMO

INTRODUCTION: Following the approval of a resident-created physician wellness program in 2016, an initial survey demonstrated majority support for the implementation of a mandatory curriculum. The purpose of this study is to survey surgical residents about the wellness curriculum six years after implementation and re-evaluate preference for mandatory participation. METHODS: In 2016, the CORE7 Wellness Program didactic sessions were integrated into the general surgery resident education curriculum. A comparison between 2016 and 2022 resident survey results was done to examine overall approval and resident experience. RESULTS: A total of 25 general surgery residents responded to the 2022 survey which equaled to a response rate of 67.5% compared to a response rate of 87.1% in 2016. Similar to the results in 2016, there was unanimous support (100%, n = 25) in favor of the ongoing development of a general surgery wellness program. The majority of residents (88% versus 85.2% in 2016) preferred quarterly "wellness half-days" remain a mandatory component of the program. In 2016, most of the residents (50%) stated that the reason for mandatory preference for wellness half-days was ease of explanation to faculty. In 2022, the reason changed to a combination of reasons with most residents (59%) selecting ease of explanation to attendings, feeling too guilty otherwise to leave the shift, and forcing the resident to think about self-care. Complaints about taking a wellness half-day from other team members increased from 29% in 2016 to 48% in 2022. CONCLUSIONS: Six years after implementation, there is unanimous support for the mandatory components of a general surgery residency wellness curriculum. Increased perceived complaints from faculty and staff about resident wellness present an opportunity for improvement.


Assuntos
Cirurgia Geral , Internato e Residência , Humanos , Inquéritos e Questionários , Currículo , Promoção da Saúde , Docentes , Cirurgia Geral/educação
4.
PLoS Comput Biol ; 20(2): e1010940, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38330044

RESUMO

Mechanical stimuli arising from fetal movements are critical factors underlying joint growth. Abnormal fetal movements negatively affect joint shape features with important implications for joint health, but the mechanisms by which mechanical forces from fetal movements influence joint growth are still unclear. In this research, we quantify zebrafish jaw joint growth in 3D in free-to-move and immobilised fish larvae between four and five days post fertilisation. We found that the main changes in size and shape in normally moving fish were in the ventrodorsal axis, while growth anisotropy was lost in the immobilised larvae. We next sought to determine the cell level activities underlying mechanoregulated growth anisotropy by tracking individual cells in the presence or absence of jaw movements, finding that the most dramatic changes in growth rates due to jaw immobility were in the ventrodorsal axis. Finally, we implemented mechanobiological simulations of joint growth with which we tested hypotheses relating specific mechanical stimuli to mechanoregulated growth anisotropy. Different types of mechanical stimulation were incorporated into the simulation to provide the mechanoregulated component of growth, in addition to the baseline (non-mechanoregulated) growth which occurs in the immobilised animals. We found that when average tissue stress over the opening and closing cycle of the joint was used as the stimulus for mechanoregulated growth, joint morphogenesis was not accurately predicted. Predictions were improved when using the stress gradients along the rudiment axes (i.e., the variation in magnitude of compression to magnitude of tension between local regions). However, the most accurate predictions were obtained when using the compressive stress gradients (i.e., the variation in compressive stress magnitude) along the rudiment axes. We conclude therefore that the dominant biophysical stimulus contributing to growth anisotropy during early joint development is the gradient of compressive stress experienced along the growth axes under cyclical loading.


Assuntos
Peixe-Zebra , Animais , Anisotropia , Estresse Mecânico
5.
J Behav Med ; 47(2): 295-307, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38127175

RESUMO

BACKGROUND: Colorectal cancer (CRC) and liver cancer are two of the leading causes of cancer death in the United States and persistent disparities in CRC and liver cancer incidence and outcomes exist. Chronic hepatitis C virus (HCV) infection is one of the main contributors to liver cancer. Effective screening for both CRC and HCV exist and are recommended for individuals based upon age, regardless of gender or sex assigned at birth. Recommendations for both screening behaviors have been recently updated. However, screening rates for both CRC and HCV are suboptimal. Targeting adoption of multiple screening behaviors has the potential to reduce cancer mortality and disparities. OBJECTIVE: To examine psychosocial factors associated with completion of CRC and HCV screenings in order to inform a multi-behavioral educational intervention that pairs CRC and HCV screening information. METHODS: A cross-sectional survey was conducted with participants (N = 50) recruited at two community health centers in Florida (United States). Kruskal-Wallis and Fisher's exact tests were used to examine associations between completion of both CRC and HCV screening, CRC and HCV knowledge, Preventive Health Model constructs (e.g., salience and coherence, response efficacy, social influence), and sociodemographic variables. RESULTS: Most participants were White (84%), female (56%), insured (80%), and reported a household income of $25,000 or less (53%). 30% reported ever previously completing both CRC and HCV screenings. Prior completion of both screening behaviors was associated with higher educational attainment (p = .014), having health insurance (p = .022), being U.S.-born (p = .043), and higher salience and coherence scores for CRC (p = .040) and HCV (p = .004). CONCLUSIONS: Findings demonstrate limited uptake of both CRC and HCV screenings among adults born between 1945 and 1965. Uptake was associated with multiple sociodemographic factors and health beliefs related to salience and coherence. Salience and coherence are modifiable factors associated with completion of both screening tests, suggesting the importance of incorporating these health beliefs in a multi-behavioral cancer education intervention. Additionally, health providers could simultaneously recommend and order CRC and HCV screening to improve uptake among this age cohort.


Assuntos
Neoplasias Colorretais , Hepatite C Crônica , Neoplasias Hepáticas , Adulto , Recém-Nascido , Humanos , Estados Unidos , Feminino , Estudos Transversais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/psicologia , Hepacivirus , Detecção Precoce de Câncer/psicologia , Programas de Rastreamento , Centros Comunitários de Saúde
6.
J Biol Chem ; 299(12): 105398, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37898404

RESUMO

Microtubules are dynamic cytoskeletal filaments that undergo stochastic switching between phases of polymerization and depolymerization-a behavior known as dynamic instability. Many important cellular processes, including cell motility, chromosome segregation, and intracellular transport, require complex spatiotemporal regulation of microtubule dynamics. This coordinated regulation is achieved through the interactions of numerous microtubule-associated proteins (MAPs) with microtubule ends and lattices. Here, we review the recent advances in our understanding of microtubule regulation, focusing on results arising from biochemical in vitro reconstitution approaches using purified multiprotein ensembles. We discuss how the combinatory effects of MAPs affect both the dynamics of individual microtubule ends, as well as the stability and turnover of the microtubule lattice. In addition, we highlight new results demonstrating the roles of protein condensates in microtubule regulation. Our overall intent is to showcase how lessons learned from reconstitution approaches help unravel the regulatory mechanisms at play in complex cellular environments.


Assuntos
Proteínas Associadas aos Microtúbulos , Tubulina (Proteína) , Segregação de Cromossomos , Citoesqueleto/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Microtúbulos/metabolismo , Tubulina (Proteína)/metabolismo , Humanos , Animais
7.
Mol Psychiatry ; 28(10): 4451-4462, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37666928

RESUMO

The APOE 2/3/4 polymorphism is the greatest genetic risk factor for Alzheimer's disease (AD). This polymorphism is also associated with variation in plasma ApoE level; while APOE*4 lowers, APOE*2 increases ApoE level. Lower plasma ApoE level has also been suggested to be a risk factor for incident dementia. To our knowledge, no large genome-wide association study (GWAS) has been reported on plasma ApoE level. This study aimed to identify new genetic variants affecting plasma ApoE level as well as to test if baseline ApoE level is associated with cognitive function and incident dementia in a longitudinally followed cohort of the Ginkgo Evaluation of Memory (GEM) study. Baseline plasma ApoE concentration was measured in 3031 participants (95.4% European Americans (EAs)). GWAS analysis was performed on 2580 self-identified EAs where both genotype and plasma ApoE data were available. Lower ApoE concentration was associated with worse cognitive function, but not with incident dementia. As expected, the risk for AD increased from E2/2 through to E4/4 genotypes (P for trend = 4.8E-75). In addition to confirming the expected and opposite associations of APOE*2 (P = 4.73E-79) and APOE*4 (P = 8.73E-12) with ApoE level, GWAS analysis revealed nine additional independent signals in the APOE region, and together they explained about 22% of the variance in plasma ApoE level. We also identified seven new loci on chromosomes 1, 4, 5, 7, 11, 12 and 20 (P range = 5.49E-08 to 5.36E-10) that explained about 9% of the variance in ApoE level. Plasma ApoE level-associated independent variants, especially in the APOE region, were also associated with AD risk and amyloid deposition in the brain, indicating that genetically determined ApoE level variation may be a risk factor for developing AD. These results improve our understanding of the genetic determinants of plasma ApoE level and their potential value in affecting AD risk.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/genética , Estudo de Associação Genômica Ampla , Apolipoproteínas E/genética , Genótipo , Polimorfismo Genético , Apolipoproteína E4/genética
9.
Mol Ecol ; 32(16): 4557-4569, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37365672

RESUMO

The broad scale distribution of population-specific genetic diversity (GDP ) across taxa remains understudied relative to species diversity gradients, despite its relevance for systematic conservation planning. We used nuclear DNA data collected from 3678 vertebrate populations across the Americas to assess the role of environmental and spatial variables in structuring the distribution of GDP , a key component of adaptive potential in the face of environmental change. We specifically assessed non-linear trends for a metric of GDP, expected heterozygosity (HE ), and found more evidence for spatial hotspots and cold spots in HE rather than a strict pattern with latitude. We also detected inconsistent relationships between HE and environmental variables, where only 11 of 30 environmental comparisons among taxa groups were statistically significant at the .05 level, and the shape of significant trends differed substantially across vertebrate groups. Only one of six taxonomic groups, freshwater fishes, consistently showed significant relationships between HE and most (four of five) environmental variables. The remaining groups had statistically significant relationships for either two (amphibians, reptiles), one (birds, mammals), or no variables (anadromous fishes). Our study highlights gaps in the theoretical foundation upon which macrogenetic predictions have been made thus far in the literature, as well as the nuances for assessing broad patterns in GDP among vertebrate groups. Overall, our results suggest a disconnect between patterns of species and genetic diversity, and underscores that large-scale factors affecting genetic diversity may not be the same factors as those shaping taxonomic diversity. Thus, careful spatial and taxonomic-specific considerations are needed for applying macrogenetics to conservation planning.


Assuntos
Biodiversidade , Vertebrados , Animais , Vertebrados/genética , Anfíbios , Mamíferos , América , Peixes , Genética Populacional , Variação Genética/genética
10.
J Cell Biol ; 222(7)2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-37184584

RESUMO

Cytoplasmic linker-associated proteins (CLASPs) regulate microtubules in fundamental cellular processes. CLASPs stabilize dynamic microtubules by suppressing microtubule catastrophe and promoting rescue, the switch-like transitions between growth and shrinkage. How CLASPs specifically modulate microtubule transitions is not understood. Here, we investigate the effects of CLASPs on the pre-catastrophe intermediate state of microtubule dynamics, employing distinct microtubule substrates to mimic the intermediate state. Surprisingly, we find that CLASP1 promotes the depolymerization of stabilized microtubules in the presence of GTP, but not in the absence of nucleotide. This activity is also observed for CLASP2 family members and a minimal TOG2-domain construct. Conversely, we find that CLASP1 stabilizes unstable microtubules upon tubulin dilution in the presence of GTP. Strikingly, our results reveal that CLASP1 drives microtubule substrates with vastly different inherent stabilities into the same slowly depolymerizing state in a nucleotide-dependent manner. We interpret this state as the pre-catastrophe intermediate state. Therefore, we conclude that CLASPs suppress microtubule catastrophe by stabilizing the intermediate state between growth and shrinkage.


Assuntos
Proteínas Associadas aos Microtúbulos , Microtúbulos , Proteínas Associadas aos Microtúbulos/metabolismo , Microtúbulos/metabolismo , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Nucleotídeos/metabolismo , Guanosina Trifosfato/metabolismo
11.
Alzheimers Dement (Amst) ; 15(2): e12429, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37124156

RESUMO

Introduction: Prior research has shown disparities in cognitive functioning across the rural-urban continuum. We examine individual- and contextual-level factors to understand how and why urbanicity shapes cognitive functioning across older adulthood. Methods: Using a nationally representative sample from 1996 to 2016 waves of the Health and Retirement Study (HRS) and growth curve models, we assess urban-suburban-exurban differences in older adult cognitive functioning. Results: Results demonstrate that older adult men and women living in exurban areas, and older adult men in suburban areas, have lower cognitive functioning scores compared to their urban peers. Educational attainment and marital status contribute to but do not fully explain these differences. There were no differences in the trajectory over age, suggesting that urbanicity disparities in cognition occur earlier in life, with average differences remaining the same across older adulthood. Discussion: Differences in cognitive functioning across urbanicity are likely due to factors accumulating prior to older adulthood.

12.
Eat Behav ; 48: 101696, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36516727

RESUMO

OBJECTIVE: The Eating Disorder Examination Questionnaire (EDE-Q) was originally validated in non-Hispanic White women and has become widely used as an assessment tool for research on eating pathology in college students. However, the original factor structure has generally failed to replicate across various samples, especially among diverse populations. The current study examined the factor structure and measurement invariance of the EDE-Q in a large sample of racially/ethnically diverse college men and women. METHOD: Participants included a diverse sample of men and women from two universities (N = 1981). Exploratory factory analysis (EFA) was conducted to examine the factor structure of the EDE-Q, followed by confirmatory factor analysis (CFA) to verify the factor structure, and establish the configural model. Furthermore, we explored the measurement invariance of the configural model by gender (i.e., men, women) and race/ethnicity (i.e., White, Black, Asian, Hispanic, and multiracial). RESULTS: EFA and CFA results suggested a three-factor, 10-item measure best fit the data, reflecting Dietary Restraint, Preoccupation and Eating Concern, and Shape/Weight Overvaluation. This measure achieved strict invariance by gender and race/ethnicity, indicating that mean comparisons across groups are meaningful. Women, relative to men, reported higher scores for all subscales. Significant differences across race/ethnicity emerged for Dietary Restraint and Shape/Weight Overvaluation in which Hispanic individuals endorsed the highest means compared to other racial/ethnic groups. DISCUSSION: The three-factor, 10-item measure is a brief, valid, and reliable measure of eating disorder psychopathology for U.S. college students.


Assuntos
Etnicidade , Transtornos da Alimentação e da Ingestão de Alimentos , Masculino , Humanos , Feminino , Psicometria/métodos , Inquéritos e Questionários , Análise Fatorial , Reprodutibilidade dos Testes
13.
Neurobiol Aging ; 122: 107-111, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36528961

RESUMO

A rare missense APOE variant (L28P; APOE*4Pittsburgh), which is present only in populations with European ancestry, has been reported to be a risk factor for late-onset Alzheimer's disease (LOAD). However, due to the complete linkage disequilibrium of L28P with APOE*4 (C112R), its independent genetic association is uncertain. The original association study implicating L28P with LOAD risk was carried out in a relatively small sample size. In the current study, we have re-evaluated this association in a large case-control sample of 15,762 White U.S. subjects and investigated its independent effect in APOE 3/4 subjects, as L28P has been observed only in the heterozygous state of APOE*4 carriers and 3/4 is the most common genotype containing the APOE*4 allele. The heterozygous carrier frequency of L28P, all with APOE*4, was about 3-fold higher in AD cases than in cognitively intact controls (0.845% vs. 0.277%). The age- and sex-adjusted meta-analysis odds ratio (OR) was 2.87 (95% CI: 1.34 - 6.13; = 0.0066). Among APOE 3/4 subjects, age- and sex-adjusted meta-analysis OR was 1.53 (95% CI: 0.70 - 3.36; p = 0.28), indicating its effect was independent of APOE*4. The lack of statistical significance appears mainly due to the low power of 4138 subjects with the 3/4 genotype (12% power at α= 0.05) compared to the required sample of 139,088 subjects with the 3/4 genotype to detect an OR of 1.5 at α= 0.05 and 80% power. Our data suggesting that L28P has an independent genetic effect on AD risk is reinforced by earlier experimental findings showing that this mutation leads to significant structural and conformational changes in the ApoE4 molecule and can induce functional defects associated with neuronal Aß42 accumulation and oxidative stress. Additional functional studies in cell-based systems and animal models will help to delineate its functional significance in the etiology of AD.


Assuntos
Doença de Alzheimer , Animais , Doença de Alzheimer/genética , Apolipoproteínas E/genética , Apolipoproteína E4/genética , Genótipo , Heterozigoto , Apolipoproteína E3/genética , Alelos
14.
J Rural Soc Sci ; 37(1)2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36299915

RESUMO

Adult children are a primary source of care for their aging parents. Parents in rural areas, however, live further from their adult children than parents in urban areas, potentially limiting the support they receive and compromising their health and ability to age in place. We use two waves of the Panel Study of Income Dynamics (2013 and 2017) to investigate the relationships among geographic proximity, adult children's instrumental and financial support, and parental health. Rural parents live further from their adult children and receive less financial support, but they are more likely to receive instrumental assistance. In addition, rural parents have worse health and more functional limitations than urban parents, and these differences persist after controlling for proximity to and support from adult children. Our findings indicate that factors beyond proximity influence the complex relationships between spatial and social boundaries and their consequences for older adults' health and well-being.

15.
SSM Popul Health ; 18: 101119, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35652089

RESUMO

Research has documented important differences in smoking rates across race/ethnicity, gender, and age. Much of the research has either focused on smoking initiation among adolescents or cessation among adults, but little is known about racial/ethnic patterns in intermittent and daily smoking across young and early middle adulthood. We therefore use the life course perspective to identify how racial/ethnic and gender differences in smoking unfold across adulthood. Analyses investigate whether racial/ethnic and gender differences exist in the likelihood of daily smoking in early middle adulthood and whether these disparities persist after the inclusion of adolescent and early midlife sociodemographic characteristics and young adult smoking patterns. Descriptive statistics and multivariate binary logistic regression analyses employ recent data from a nationally representative sample of adults using the National Longitudinal Study of Adolescent to Adult Health (Add Health; N = 8,506). We find evidence that life course patterns of smoking differ across race/ethnicity and gender subgroups. In early middle adulthood (ages 33-44), White women are more likely to smoke daily than Black or Hispanic women. In contrast, there are no significant differences between White and Black men, but White men are more likely to smoke daily than Hispanic men. These racial/ethnic differences are no longer significant for men when previous smoking is controlled, suggesting that early young adult smoking plays an important role in the development of smoking disparities across race/ethnicity. Further, we find that young adult intermittent smoking is associated with daily smoking in early midlife, and this relationship is stronger for Black, compared to White, men and women. Although Black women display lower odds of daily smoking in early midlife compared to White women, they exhibit a higher risk of transitioning from intermittent to daily smoking. These results highlight the importance of considering a greater diversity of life course patterns in smoking across race/ethnicity and gender in future research and policies.

16.
J Anat ; 241(2): 358-371, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35510779

RESUMO

In early limb embryogenesis, synovial joints acquire specific shapes which determine joint motion and function. The process by which the opposing cartilaginous joint surfaces are moulded into reciprocal and interlocking shapes, called joint morphogenesis, is one of the least understood aspects of joint formation and the cell-level dynamics underlying it are yet to be unravelled. In this research, we quantified key cellular dynamics involved in growth and morphogenesis of the zebrafish jaw joint and synthesised them in a predictive computational simulation of joint development. Cells in larval zebrafish jaw joints labelled with cartilage markers were tracked over a 48-h time window using confocal imaging. Changes in distance and angle between adjacent cell centroids resulting from cell rearrangement, volume expansion and extracellular matrix (ECM) deposition were measured and used to calculate the rate and direction of local tissue deformations. We observed spatially and temporally heterogeneous growth patterns with marked anisotropy over the developmental period assessed. There was notably elevated growth at the level of the retroarticular process of the Meckel's cartilage, a feature known to undergo pronounced shape changes during zebrafish development. Analysis of cell dynamics indicated a dominant role for cell volume expansion in growth, with minor influences from ECM volume increases and cell intercalation. Cell proliferation in the joint was minimal over the timeframe of interest. Synthesising the dynamic cell data into a finite element model of jaw joint development resulted in accurate shape predictions. Our biofidelic computational simulation demonstrated that zebrafish jaw joint growth can be reasonably approximated based on cell positional information over time, where cell positional information derives mainly from cell orientation and cell volume expansion. By modifying the input parameters of the simulation, we were able to assess the relative contributions of heterogeneous growth rates and of growth orientation. The use of uniform rather than heterogeneous growth rates only minorly impacted the shape predictions, whereas isotropic growth fields resulted in altered shape predictions. The simulation results suggest that growth anisotropy is the dominant influence on joint growth and morphogenesis. This study addresses the gap of the cellular processes underlying joint morphogenesis, with implications for understanding the aetiology of developmental joint disorders such as developmental dysplasia of the hip and arthrogryposis.


Assuntos
Cartilagem , Peixe-Zebra , Animais , Arcada Osseodentária , Larva , Morfogênese , Articulação Temporomandibular
17.
Mol Biol Cell ; 33(3): ar22, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35108073

RESUMO

Microtubules (MTs) are cytoskeletal fibers that undergo dynamic instability (DI), a remarkable process involving phases of growth and shortening separated by stochastic transitions called catastrophe and rescue. Dissecting DI mechanism(s) requires first characterizing and quantifying these dynamics, a subjective process that often ignores complexity in MT behavior. We present a Statistical Tool for Automated Dynamic Instability Analysis (STADIA) that identifies and quantifies not only growth and shortening, but also a category of intermediate behaviors that we term "stutters." During stutters, the rate of MT length change tends to be smaller in magnitude than during typical growth or shortening phases. Quantifying stutters and other behaviors with STADIA demonstrates that stutters precede most catastrophes in our in vitro experiments and dimer-scale MT simulations, suggesting that stutters are mechanistically involved in catastrophes. Related to this idea, we show that the anticatastrophe factor CLASP2γ works by promoting the return of stuttering MTs to growth. STADIA enables more comprehensive and data-driven analysis of MT dynamics compared with previous methods. The treatment of stutters as distinct and quantifiable DI behaviors provides new opportunities for analyzing mechanisms of MT dynamics and their regulation by binding proteins.


Assuntos
Gagueira , Citoesqueleto/metabolismo , Humanos , Microtúbulos/metabolismo , Gagueira/metabolismo , Tubulina (Proteína)/metabolismo
18.
J Health Soc Behav ; 63(1): 125-141, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34806448

RESUMO

Combining theories of health lifestyles-interrelated health behaviors arising from group-based identities-with those of network and behavior change, we investigated network characteristics of health lifestyles and the role of influence and selection processes underlying these characteristics. We examined these questions in two high schools using longitudinal, complete friendship network data from the National Longitudinal Study of Adolescent to Adult Health. Latent class analyses characterized each school's predominant health lifestyles using several health behavior domains. School-specific stochastic actor-based models evaluated the bidirectional relationship between friendship networks and health lifestyles. Predominant lifestyles remained stable within schools over time, even as individuals transitioned between lifestyles. Friends displayed greater similarity in health lifestyles than nonfriend dyads. Similarities resulted primarily from teens' selection of friends with similar lifestyles but also from teens influencing their peers' lifestyles. This study demonstrates the salience of health lifestyles for adolescent development and friendship networks.


Assuntos
Comportamento do Adolescente , Grupo Associado , Adolescente , Amigos , Humanos , Estilo de Vida , Estudos Longitudinais , Instituições Acadêmicas
19.
Elife ; 102021 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-34970964

RESUMO

Sjögren's syndrome nuclear autoantigen-1 (SSNA1/NA14) is a microtubule-associated protein with important functions in cilia, dividing cells, and developing neurons. However, the direct effects of SSNA1 on microtubules are not known. We employed in vitro reconstitution with purified proteins and TIRF microscopy to investigate the activity of human SSNA1 on dynamic microtubule ends and lattices. Our results show that SSNA1 modulates all parameters of microtubule dynamic instability-slowing down the rates of growth, shrinkage, and catastrophe, and promoting rescue. We find that SSNA1 forms stretches along growing microtubule ends and binds cooperatively to the microtubule lattice. Furthermore, SSNA1 is enriched on microtubule damage sites, occurring both naturally, as well as induced by the microtubule severing enzyme spastin. Finally, SSNA1 binding protects microtubules against spastin's severing activity. Taken together, our results demonstrate that SSNA1 is both a potent microtubule-stabilizing protein and a novel sensor of microtubule damage; activities that likely underlie SSNA1's functions on microtubule structures in cells.


Assuntos
Autoantígenos/genética , Microtúbulos/fisiologia , Proteínas Nucleares/genética , Linhagem Celular , Humanos , Proteínas Associadas aos Microtúbulos/metabolismo , Microtúbulos/patologia , Espastina/metabolismo
20.
Popul Res Policy Rev ; 40(5): 1085-1117, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34720278

RESUMO

Lifestyles are a long-theorized aspect of social inequalities that root individual behaviors in social group differences. Although the health lifestyle construct is an important advance for understanding social inequalities and health behaviors, research has not theorized or investigated the longitudinal development of health lifestyles from infancy through the transition to school. This study documented children's longitudinal health lifestyle pathways, articulated and tested a theoretical framework of health lifestyle development in early life, and assessed associations with kindergarten cognition, socioemotional behavior, and health. Latent class analyses identified health lifestyle pathways using the US Early Childhood Longitudinal Study - Birth Cohort (ECLS-B; N≈6,550). Children's health lifestyle pathways were complex, combining healthier and unhealthier behaviors and changing with age. Social background prior to birth was associated with health lifestyle pathways, as were parents' resources, health behaviors, and non-health-focused parenting. Developing health lifestyle pathways were related to kindergarten cognition, behavior, and health net of social background and other parent influences. Thus, family context is important for the development of complex health lifestyle pathways across early childhood, which have implications for school preparedness and thus for social inequalities and well-being throughout life. Developing health lifestyles both reflect and reproduce social inequalities across generations.

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