Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 159
Filtrar
1.
PM R ; 16(4): 347-355, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38529764

RESUMO

BACKGROUND: In National Collegiate Athletic Association (NCAA) soccer athletes, men have higher rates of hip and groin strains, whereas women have higher rates of knee ligament injuries. Strength imbalances of the hip and thigh, specifically in agonist-antagonist muscles, are known risk factors for these injuries. OBJECTIVE: To perform hip and thigh strength assessments in NCAA soccer players to evaluate for differences between genders and correlations with gender-specific injury patterns. DESIGN: With a handheld dynamometer, weight-normalized isometric strength of six muscle groups (hip abductors, hip adductors, hip flexors, hip extensors, knee flexors, knee extensors) was calculated in NCAA soccer players. The strength ratio of each agonist-antagonist muscle was also calculated (hip abductors/adductors, hip flexors/extensors, knee extensors/flexors). PARTICIPANTS: Thirty-six NCAA soccer players (18 men, 18 women) from a single NCAA Division III institution. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Weight-normalized strength of six muscle groups and their agonist-antagonist strength ratios were compared between genders using linear mixed-effects models. RESULTS: Compared with male players, female players had decreased weight-normalized strength for hip abduction (0.170 vs. 0.204, p = .012) and hip extension (0.172 vs. 0.211, p = .021). Otherwise, weight-normalized strength was similar between genders. When comparing agonist-antagonist strength ratios, there was a significant difference between female and male players for hip flexion:extension (1.70 vs. 1.35, p = .008), whereas the hip abduction: adduction ratio did not reach statistical significance (1.45 vs. 1.62, p = .080). CONCLUSIONS: NCAA male and female soccer players had different hip strength profiles that fit their injury patterns. Male NCAA soccer players have higher rates of hip and groin strains, and men in the cohort had strength ratios that were deficient in the hip flexors and adductors compared with women. Female NCAA soccer players have higher rates of knee sprains and anterior cruciate ligament tears, and women in the cohort had strength ratios that were deficient in the hip abductors and extensors, which function to stabilize the knee. These strength disparities could be the focus of future gender-specific soccer injury prevention programs.


Assuntos
Traumatismos em Atletas , Futebol , Entorses e Distensões , Humanos , Masculino , Feminino , Futebol/lesões , Traumatismos em Atletas/epidemiologia , Extremidade Inferior , Universidades , Força Muscular
2.
Nature ; 627(8004): 604-611, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38448582

RESUMO

Human brains vary across people and over time; such variation is not yet understood in cellular terms. Here we describe a relationship between people's cortical neurons and cortical astrocytes. We used single-nucleus RNA sequencing to analyse the prefrontal cortex of 191 human donors aged 22-97 years, including healthy individuals and people with schizophrenia. Latent-factor analysis of these data revealed that, in people whose cortical neurons more strongly expressed genes encoding synaptic components, cortical astrocytes more strongly expressed distinct genes with synaptic functions and genes for synthesizing cholesterol, an astrocyte-supplied component of synaptic membranes. We call this relationship the synaptic neuron and astrocyte program (SNAP). In schizophrenia and ageing-two conditions that involve declines in cognitive flexibility and plasticity1,2-cells divested from SNAP: astrocytes, glutamatergic (excitatory) neurons and GABAergic (inhibitory) neurons all showed reduced SNAP expression to corresponding degrees. The distinct astrocytic and neuronal components of SNAP both involved genes in which genetic risk factors for schizophrenia were strongly concentrated. SNAP, which varies quantitatively even among healthy people of similar age, may underlie many aspects of normal human interindividual differences and may be an important point of convergence for multiple kinds of pathophysiology.


Assuntos
Envelhecimento , Astrócitos , Neurônios , Córtex Pré-Frontal , Esquizofrenia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Envelhecimento/metabolismo , Envelhecimento/patologia , Astrócitos/citologia , Astrócitos/metabolismo , Astrócitos/patologia , Colesterol/metabolismo , Cognição , Neurônios GABAérgicos/metabolismo , Predisposição Genética para Doença , Glutamina/metabolismo , Saúde , Individualidade , Inibição Neural , Plasticidade Neuronal , Neurônios/citologia , Neurônios/metabolismo , Neurônios/patologia , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia , Esquizofrenia/genética , Esquizofrenia/metabolismo , Esquizofrenia/patologia , Análise da Expressão Gênica de Célula Única , Sinapses/genética , Sinapses/metabolismo , Sinapses/patologia , Membranas Sinápticas/química , Membranas Sinápticas/metabolismo
3.
J Chromatogr A ; 1718: 464710, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38330727

RESUMO

The separation of vitamin A acetate isomers is essential for quality assurance of e.g. nutrition supplements, cosmetics, and pharmaceutical ingredients. High performance liquid chromatography (HPLC) is currently the most suitable analytical method for tackling this challenging separation task. However, the existing methods based on normal phase chromatography (NPC) are poorly reproducible due to the typical disadvantages of NPC, such as long equilibration times and fluctuation in retention factors. A new reversed phase method developed in our labs allows the separation of the isomers applying a chiral stationary phase (CSP). This phase consists of an immobilized polysaccharide which can be used in every chromatographic mode. However, they are not typically used in reversed phase mode. Through the screening of various stationary phases with different polysaccharide based chiral selectors, the choice of the ideal stationary phase could be confirmed, allowing to draw conclusions about the retention mechanism. The CSP Chiralpak IG-3 was found to be the most suitable among the examined. Regarding the separation mechanism, the spatial helical structure of the polysaccharide derivatives was confirmed to be of particular significance. In addition to the stationary phase, the mobile phase was tested for optimization regarding composition, gradient parameters as well as temperature using chromatographic method optimization software for the sake of method robustness.


Assuntos
Amilose , Diterpenos , Polissacarídeos , Ésteres de Retinil , Amilose/química , Estereoisomerismo , Polissacarídeos/química , Cromatografia Líquida de Alta Pressão/métodos
4.
bioRxiv ; 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38260461

RESUMO

Human brains vary across people and over time; such variation is not yet understood in cellular terms. Here we describe a striking relationship between people's cortical neurons and cortical astrocytes. We used single-nucleus RNA-seq to analyze the prefrontal cortex of 191 human donors ages 22-97 years, including healthy individuals and persons with schizophrenia. Latent-factor analysis of these data revealed that in persons whose cortical neurons more strongly expressed genes for synaptic components, cortical astrocytes more strongly expressed distinct genes with synaptic functions and genes for synthesizing cholesterol, an astrocyte-supplied component of synaptic membranes. We call this relationship the Synaptic Neuron-and-Astrocyte Program (SNAP). In schizophrenia and aging - two conditions that involve declines in cognitive flexibility and plasticity 1,2 - cells had divested from SNAP: astrocytes, glutamatergic (excitatory) neurons, and GABAergic (inhibitory) neurons all reduced SNAP expression to corresponding degrees. The distinct astrocytic and neuronal components of SNAP both involved genes in which genetic risk factors for schizophrenia were strongly concentrated. SNAP, which varies quantitatively even among healthy persons of similar age, may underlie many aspects of normal human interindividual differences and be an important point of convergence for multiple kinds of pathophysiology.

5.
Semin Arthritis Rheum ; 64: 152343, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38118370

RESUMO

OBJECTIVE: To define and select rheumatoid arthritis (RA)-specific core domain set for Longitudinal Observational Studies (LOS) within the Outcome Measures in Rheumatology (OMERACT) framework. METHODS: A three-round online Delphi exercise, including patient research partners (PRPs) and other community partners in healthcare, was conducted. Domains scored 7-9 (i.e., critically important to include) by ≥ 70 % of participants in both groups were included. Items were consolidated in a subsequent dedicated meeting. RESULTS: Nineteen domains scored ≥ 70 % consensus in both groups. The focus group refined these into a list of twelve domains. CONCLUSION: The achieved consensus will inform the next steps of developing the core domain set for LOS in RA.


Assuntos
Artrite Reumatoide , Reumatologia , Humanos , Consenso , Estudos Longitudinais , Avaliação de Resultados em Cuidados de Saúde
6.
Demography ; 60(6): 1711-1720, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37982579

RESUMO

In this research note, we demonstrate that trends in the likelihood of child support agreements differ by marital history (i.e., never-married vs. ever-married) and by whether measures rely on the stock of families (i.e., all those in which children live apart from a parent) or the flow (i.e., those that include children who newly live apart from a parent) in a given year. While previous research has highlighted difference by marital history, the contrast between stock and flow is a new contribution. Trends are typically measured with reference to the stock of cases, even while the flow of cases, which more immediately reflects concurrent policy changes, is more relevant in many contexts. Interpretations of recent declines in child support agreements in the stock of cases-referenced as evidence for both mandating participation and the impracticality of requiring child support-may be better informed by considering the flow of cases. We find the flow of previously married mothers increasingly likely to have child support agreements while the likelihood is relatively consistent over time for never-married mothers. For both groups, using the flow measure, we find notable increases in agreements without payments due in the most recent period. These findings underscore the importance of differentiating stock and flow, and by marital history, in considering the proportion with agreements as an indicator of the effectiveness of current policy.


Assuntos
Custódia da Criança , Características da Família , Feminino , Criança , Humanos , Pais , Casamento , Mães
8.
Fam Med ; 55(8): 525-529, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37696021

RESUMO

BACKGROUND AND OBJECTIVES: As the family medicine community continues to adapt to interview season changes secondary to the effects of the COVID-19 pandemic, discussions are underway regarding new options to improve the overall success and satisfaction of resident recruiting. Tools such as preference signaling, interview capping, and supplementary applications are options that have been investigated, and in some cases implemented, by other specialties for their recruiting seasons. Family medicine as a specialty is now actively scrutinizing the benefits and drawbacks of these tools. METHODS: The fall 2021 CERA program directors' omnibus online cross-sectional survey invited family medicine program directors to provide their perceptions of these tools. Descriptive statistics and multivariate logistic regressions were conducted. RESULTS: Two-thirds of the 262 program director respondents (42% response rate, n=184) supported policies for preference signaling and a national interview cap; however, support was mixed for the use of supplemental applications. CONCLUSIONS: Because the survey results indicated a high level of support for using these innovative new tools during recruitment season, family medicine should take action to implement these programs/policies.


Assuntos
COVID-19 , Internato e Residência , Humanos , Estudos Transversais , Medicina de Família e Comunidade , Pandemias , Estações do Ano
9.
iScience ; 26(7): 106995, 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37534135

RESUMO

Emerging evidence of species divergent features of astrocytes coupled with the relative inaccessibility of human brain tissue underscore the utility of human pluripotent stem cell (hPSC) technologies for the generation and study of human astrocytes. However, existing approaches for hPSC-astrocyte generation are typically lengthy or require intermediate purification steps. Here, we establish a rapid and highly scalable method for generating functional human induced astrocytes (hiAs). These hiAs express canonical astrocyte markers, respond to pro-inflammatory stimuli, exhibit ATP-induced calcium transients and support neuronal network development. Moreover, single-cell transcriptomic analyses reveal the generation of highly reproducible cell populations across individual donors, mostly resembling human fetal astrocytes. Finally, hiAs generated from a trisomy 21 disease model identify expected alterations in cell-cell adhesion and synaptic signaling, supporting their utility for disease modeling applications. Thus, hiAs provide a valuable and practical resource for the study of basic human astrocyte function and dysfunction in disease.

10.
Chemistry ; 29(63): e202302188, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37566451

RESUMO

This work reports the effect of Pd(II) as chemical effector on an acylhydrazone-based dynamic covalent library (DCL) in biphasic systems (water/chloroform). The constituents of the DCL are self-built and distributed in the two phases, two of them are lipophilic enough to play the role of a carrier agent that may transfer Pd(II) from the aqueous phase to the organic phase. Upon addition of Pd(II), the DCL of components exhibits a strong amplification of the constituent that is the most adapted to stabilize Pd(II) in chloroform as well as its agonist in water. This evolution is driven by the combination of the interaction of the DCL with Pd(II) and the presence of the two phases. This study paves the way to a novel approach for liquid/liquid extraction and metal recovery by means of adaptive extractant species generated in situ by a DCL.

11.
J Sep Sci ; 46(20): e2300204, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37568243

RESUMO

In striving for the best possible separation, the selectivity of stationary phases as an optimization parameter is often underestimated although there are many ways to influence this powerful tool. This review serves to provide an insight into the various ways of adapting the selectivity of a separation in liquid chromatography. Approaches via temperature and flow rate tuning are discussed as a basis followed by focusing on the stationary phase as the superior optimization parameter. Highly selective stationary phases hereby provide an advantage for groups of similar analytes. For more complex mixtures, separations can be improved using mixed-mode technologies where different retention mechanisms are combined. Serial coupling, mixed-bed columns, and stationary phase optimized selectivity liquid chromatography provide solutions to various degrees. Finally, the advantages of stationary phase tuning over adaption of mobile phase and/or temperature are presented in terms of optimum application range.

12.
ACS Appl Mater Interfaces ; 15(25): 30707-30716, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37318840

RESUMO

Metal-organic frameworks (MOFs) show promise for the capture of greenhouse gases. To be used at a large scale in fixed-bed processes, their shaping under a hierarchical structure is mandatory and remains a major challenge, while keeping available their high specific surface area. For that purpose, we propose herein an original method based on the stabilization of a paraffin-in-water Pickering emulsion by a fluorinated Zr MOF (UiO-66(F4)) with polyHIPEs (polymers from high internal phase emulsions) strategy consisting of the polymerization of monomers in the external phase. After polymerization of the continuous phase and elimination of the paraffin, a hierarchically structured monolith is obtained with the UiO-66(F4) particles embedded in the polymer wall and covering the internal porosity. To avoid the pore blocking induced by the embedment of the MOF particles, our strategy was to modify their hydrophilic/hydrophobic balance with a controlled adsorption of hydrophobic molecules (perfluorooctanoic acid, PFOA) on the UiO-66(F4) particles. This will induce a displacement of the MOF position at the paraffin-water interface in the emulsion and then make the particles less embedded into the polymer wall. This leads to the formation of hierarchically structured monoliths integrating UiO-66(F4) particles with higher accessibility, maintaining their original properties and allowing their application in fixed-bed processes. This strategy was demonstrated by N2 and CO2 capture, and we believe that such original strategy could be applied to other MOF materials.

13.
Materials (Basel) ; 16(11)2023 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-37297304

RESUMO

Once on Mars, maintenance and repair will be crucial for humans as supply chains including Earth and Mars will be very complex. Consequently, the raw material available on Mars must be processed and used. Factors such as the energy available for material production play just as important a role as the quality of the material that can be produced and the quality of its surface. To develop and technically implement a process chain that meets the challenge of producing spare parts from oxygen-reduced Mars regolith, this paper addresses the issue of low-energy handling. Expected statistically distributed high roughnesses of sintered regolith analogs are approximated in this work by parameter variation in the PBF-LB/M process. For low-energy handling, a dry-adhesive microstructure is used. Investigations are carried out to determine the extent to which the rough surface resulting from the manufacturing process can be smoothed by deep-rolling in such a way that the microstructure adheres and enables samples to be transported. For the investigated AlSi10Mg samples (12 mm × 12 mm × 10 mm), the surface roughness varies in a wide range from Sa 7.7 µm to Sa 64 µm after the additive manufacturing process, and pull-off stresses of up to 6.99 N/cm2 could be realized after deep-rolling. This represents an increase in pull-off stresses by a factor of 392.94 compared to the pull-off stresses before deep-rolling, enabling the handling of even larger specimens. It is noteworthy that specimens with roughness values that were previously difficult to handle can be treated post-deep-rolling, indicating a potential influence of additional variables that describe roughness or ripples and are associated with the adhesion effect of the microstructure of the dry adhesive.

14.
Cells ; 12(6)2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36980307

RESUMO

Recently, the long-term use of sedative agents in the neonatal intensive care unit (NICU) has raised concerns about neurodevelopmental outcomes in exposed neonates. Midazolam (MDZ), a common neonatal sedative in the NICU, has been suggested to increase learning disturbances and cognitive impairment in children. However, molecular mechanisms contributing to such outcomes with long-term MDZ use during the early stages of life remain unclear. In this study, we for the first time elucidate the role of brain-derived extracellular vesicles (BDEVs), including mining the BDEV proteome post long-term MDZ exposure during early development. Employing our previously established rodent model system that mimics the exposure of MDZ in the NICU using an increasing dosage regimen, we isolated BDEVs from postnatal 21-days-old control and MDZ groups using a differential sucrose density gradient. BDEVs from the control and MDZ groups were then characterized using a ZetaView nanoparticle tracking analyzer and transmission electron microscopy analysis. Next, using RT-qPCR, we examined the expression of key ESCRT-related genes involved in EV biogenesis. Lastly, using quantitative mass spectrometry-based proteomics, we mined the BDEV protein cargo that revealed key differentially expressed proteins and associated molecular pathways to be altered post long-term MDZ exposure. Our study characterized the proteome in BDEV cargo from long-term MDZ exposure at early development. Importantly, we identified and validated the expression of YWHAH as a potential target for further characterization of its downstream mechanism and a potential biomarker for the early onset of neurodevelopment and neurodegenerative diseases. Overall, the present study demonstrated long-term exposure to MDZ at early development stages could influence BDEV protein cargo, which potentially impact neural functions and behavior at later stages of development.


Assuntos
Proteínas 14-3-3 , Vesículas Extracelulares , Midazolam , Animais , Ratos , Biomarcadores , Encéfalo , Vesículas Extracelulares/metabolismo , Hipnóticos e Sedativos/efeitos adversos , Midazolam/efeitos adversos , Midazolam/farmacologia , Modelos Biológicos , Proteoma
15.
Cell Stem Cell ; 30(3): 312-332.e13, 2023 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-36796362

RESUMO

Human genome variation contributes to diversity in neurodevelopmental outcomes and vulnerabilities; recognizing the underlying molecular and cellular mechanisms will require scalable approaches. Here, we describe a "cell village" experimental platform we used to analyze genetic, molecular, and phenotypic heterogeneity across neural progenitor cells from 44 human donors cultured in a shared in vitro environment using algorithms (Dropulation and Census-seq) to assign cells and phenotypes to individual donors. Through rapid induction of human stem cell-derived neural progenitor cells, measurements of natural genetic variation, and CRISPR-Cas9 genetic perturbations, we identified a common variant that regulates antiviral IFITM3 expression and explains most inter-individual variation in susceptibility to the Zika virus. We also detected expression QTLs corresponding to GWAS loci for brain traits and discovered novel disease-relevant regulators of progenitor proliferation and differentiation such as CACHD1. This approach provides scalable ways to elucidate the effects of genes and genetic variation on cellular phenotypes.


Assuntos
Células-Tronco Neurais , Infecção por Zika virus , Zika virus , Humanos , Células-Tronco Neurais/metabolismo , Diferenciação Celular/genética , Encéfalo/metabolismo , Zika virus/metabolismo , Expressão Gênica , Proteínas de Membrana/metabolismo , Proteínas de Ligação a RNA/metabolismo
16.
Soc Sci Res ; 110: 102850, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36796990

RESUMO

Research on child support compliance has focused on the characteristics of noncustodial parents (NCPs) that are associated with compliance, finding that compliance with child support orders is primarily related to the ability to pay support as demonstrated by earnings. Yet, there is evidence linking social support networks to both earnings and noncustodial parents' relationships with children. Using a social poverty framework, we show that relatively few NCPs are completely isolated: most have at least some people in their network who can loan money, provide a place to stay, or provide a ride. We explore whether the size of these instrumental support networks is positively linked to child support compliance both directly and indirectly through earnings. We find evidence of a direct association between instrumental support network size and child support compliance, but no evidence of an indirect association via increased earnings. These findings suggest the importance for researchers and child support practitioners to consider the contextual and relational factors of the social networks in which parents are embedded, and to more thoroughly examine the process by which support from one's network can lead to child support compliance.


Assuntos
Custódia da Criança , Pais , Criança , Humanos , Renda , Pobreza , Apoio Social
17.
Fam Med ; 55(2): 107-110, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36787518

RESUMO

BACKGROUND AND OBJECTIVES: In 2020 the Accreditation Council on Graduate Medical Education (ACGME) became the sole accrediting body for osteopathic and allopathic residency programs, with an option for programs to apply for Osteopathic Recognition (OR) to distinguish their training in osteopathic principles and practice. There is limited research regarding this transition. The goal of our study was to assess the perceived value of OR and perceived difficulty of obtaining OR for family medicine residency programs. METHODS: We performed analyses regarding the difficulty of obtaining OR status and the value of OR and Osteopathic Principles and Practice (OPP) using questions on the 2020 Council of Academic Family Medicine Educational Research Alliance (CERA) omnibus survey. RESULTS: Of the 280 program directors (PD) responding, 69 (24.6%) had OR status, 126 (45.0%) were considering applying or would apply if needed resources were available, and 85 (30.4%) were not considering OR. Of the 73 PDs reporting on experience with the OR process, 28 (38.4%) found it "very smooth," 30 (41.1%) found it "a little bumpy," and 15 (20.5%) found it "very bumpy"; 87.0% of PDs (60 of 69) with OR felt it had value in recruiting DO students and 31.8% (22/69) in recruiting MD students; 86.9% of programs with OR status perceived OPP to be somewhat or very valuable in enhancing patient satisfaction compared to 77% of those considering OR and 44.7% not considering OR. CONCLUSIONS: Program directors perceive value in OR status for recruiting and in osteopathic practice for patient care. Since 75.4% of responding program directors have or are interested in achieving OR status, further research is needed on its benefits and barriers.


Assuntos
Internato e Residência , Medicina Osteopática , Médicos Osteopáticos , Humanos , Estados Unidos , Medicina Osteopática/educação , Educação de Pós-Graduação em Medicina , Inquéritos e Questionários , Acreditação
18.
Cell Rep ; 42(1): 111988, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36640364

RESUMO

The maturation of neurons and the development of synapses, although emblematic of neurons, also relies on interactions with astrocytes and other glia. Here, to study the role of glia-neuron interactions, we analyze the transcriptomes of human pluripotent stem cell (hPSC)-derived neurons, from 80 human donors, that were cultured with or without contact with glial cells. We find that the presence of astrocytes enhances synaptic gene-expression programs in neurons when in physical contact with astrocytes. These changes in neurons correlate with increased expression, in the cocultured glia, of genes that encode synaptic cell adhesion molecules. Both the neuronal and astrocyte gene-expression programs are enriched for genes associated with schizophrenia risk. Our results suggest that astrocyte-expressed genes with synaptic functions are associated with stronger expression of synaptic genetic programs in neurons, and they suggest a potential role for astrocyte-neuron interactions in schizophrenia.


Assuntos
Astrócitos , Esquizofrenia , Humanos , Astrócitos/metabolismo , Adesão Celular/genética , Esquizofrenia/genética , Esquizofrenia/metabolismo , Neurônios/metabolismo , Neuroglia , Sinapses/fisiologia
19.
Cell Rep ; 42(1): 111896, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36596304

RESUMO

Human pluripotent stem cells (hPSCs) are a powerful tool for disease modeling of hard-to-access tissues (such as the brain). Current protocols either direct neuronal differentiation with small molecules or use transcription-factor-mediated programming. In this study, we couple overexpression of transcription factor Neurogenin2 (Ngn2) with small molecule patterning to differentiate hPSCs into lower induced motor neurons (liMoNes/liMNs). This approach induces canonical MN markers including MN-specific Hb9/MNX1 in more than 95% of cells. liMNs resemble bona fide hPSC-derived MN, exhibit spontaneous electrical activity, express synaptic markers, and can contact muscle cells in vitro. Pooled, multiplexed single-cell RNA sequencing on 50 hPSC lines reveals reproducible populations of distinct subtypes of cervical and brachial MNs that resemble their in vivo, embryonic counterparts. Combining small molecule patterning with Ngn2 overexpression facilitates high-yield, reproducible production of disease-relevant MN subtypes, which is fundamental in propelling our knowledge of MN biology and its disruption in disease.


Assuntos
Sinais (Psicologia) , Células-Tronco Pluripotentes Induzidas , Humanos , Diferenciação Celular , Neurônios Motores/metabolismo , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica , Células-Tronco Pluripotentes Induzidas/metabolismo , Proteínas de Homeodomínio/metabolismo
20.
Fam Process ; 62(3): 1196-1216, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36216325

RESUMO

Families (and sometimes courts) make important decisions regarding child physical custody arrangements post-separation, and shared parenting arrangements are increasingly common in most developed countries. Shared arrangements may be differentially associated with parental satisfaction, and these associations may vary across countries. Using data from surveys of separated mothers in Wisconsin and Finland, the present study explores this possibility and is guided by three aims: (a) to identify child and family characteristics associated with sole and shared child placements 6 or more years after separation; (b) to estimate associations of children's post-separation placements with maternal satisfaction with placements and expense sharing; (c) to examine whether the relationship between post-separation placement and maternal satisfaction varies by mothers' earnings and the quality of parents' relationships. We find that Finnish mothers with shared placement are more satisfied with their placement than are their counterparts with sole placement, while we find the inverse is true for Wisconsin mothers. Moreover, parental satisfaction with shared placement, overall and relative to sole placement, varies greatly depending on the quality of a mother's relationship with the other parent; and differences in relationship quality in Wisconsin and Finland may help explain the difference in satisfaction with shared placement in the two locations. In both Finland and Wisconsin, we find mothers with shared placement are more satisfied with the way expenses are shared between parents than are mothers with sole placement. Associations between placement and satisfaction are robust to extensive controls for child and maternal characteristics.


Assuntos
Custódia da Criança , Divórcio , Feminino , Humanos , Criança , Finlândia , Wisconsin , Mães , Satisfação Pessoal
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...