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1.
PLoS One ; 19(3): e0301576, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38547093

RESUMO

[This corrects the article DOI: 10.1371/journal.pone.0291682.].

2.
Opt Lett ; 49(5): 1297-1300, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38426997

RESUMO

The successful demonstration of long-lived nitric oxide (NO) fluorescence for molecular tagging velocimetry (MTV) measurements is described in this Letter. Using 1 + 1 resonance-enhanced multiphoton ionization (REMPI) of NO at a wavelength near 226 nm, targeting the overlapping Q1(7) and Q21(7) lines of the A-X (0, 0) electronic system, the lifetime of the NO MTV signal was observed to be approximately 8.6 µs within a 100-Torr cell containing 2% NO in nitrogen. This is in stark contrast to the commonly reported single photon NO fluorescence, which has a much shorter calculated lifetime of approximately 43 ns at this pressure and NO volume fraction. While the shorter lifetime fluorescence can be useful for molecular tagging velocimetry with single laser excitation within very high-speed flows at some thermodynamic conditions, the longer lived fluorescence shows the potential for an order of magnitude more accurate and precise velocimetry, particularly within lower speed regions of hypersonic flow fields such as wakes and boundary layers. The physical mechanism responsible for the generation of this long-lived signal is detailed. Furthermore, the effectiveness of this technique is showcased in a high-speed jet flow, where it is employed for precise flow velocity measurements.

3.
Appl Opt ; 63(5): 1247-1257, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38437304

RESUMO

An injection-seeded, burst-mode optical parametric oscillator (OPO) operating at a repetition rate of 100 kHz is used to demonstrate the multiline molecular tagging velocimetry of an underexpanded jet using nitric oxide fluorescence. The very narrow linewidth of the OPO system, along with the relatively high pulse energies of the burst-mode system, enables efficient single-photon excitation of nitric oxide along multiple laser beam lines at a high repetition rate. Simultaneous one-dimensional velocity profile measurements were obtained of an underexpanded jet system at six different locations using a reference initial image and single-shot delayed images. A methodology for calculating the uncertainty of single-shot velocity is also described. Mean and root-mean-square velocity profiles are obtained at multiple locations simultaneously over a sampling time of 1 ms. The high-repetition-rate velocity measurements also appear to capture the onset of velocity oscillations and has the potential to reveal velocity frequency content occurring in the tens of kHz. The demonstrated velocimetry technique could be paired with other emerging burst-mode laser capabilities for a quantitative multiparameter gas property or multicomponent gas velocity measurements for supersonic and hypersonic flows, especially within ground test facilities that are limited to very short run durations.

4.
PLoS One ; 18(9): e0291682, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37725630

RESUMO

BACKGROUND: Community-related health assessments have been shown to improve several outcomes in socioeconomically disadvantaged populations with comorbid chronic health conditions. However, while it is recognized that modifiable social determinant of health (SDH) factors might be responsible for up to 60% of preventable deaths, it is not yet standard of care to routinely screen and address these at preventive health appointments. The objective of this study was to identify the social needs of socioeconomically disadvantaged patients. METHODS: We performed a retrospective review of the socioeconomic screening questionnaires distributed to under- and uninsured patients seen at a medical student-run free primary care-based community clinic. This study included participants of all ages (0 and up), genders, languages, and ethnicities who filled out the social screening questionnaire. Socioeconomic screening questionnaires assessed the need for critical resources such as food, housing, utilities, finances, transportation, childcare, employment, education, legal support, companionship, health literacy, and community assistance. The primary study outcome was to identify unmet social needs of our medical student-run free clinic patients. We secondarily sought to identify associations between these needs and chronic health conditions. We hypothesized that patients with multiple chronic health problems and financial stressors would have the highest requests for resources. RESULTS: Our retrospective review identified 264 uninsured participants who were evaluated for social needs using a screening questionnaire. Participants who reported unmet social needs had significantly more cardiovascular risk factors than those who did not. Cardiovascular comorbidities and a history of psychiatric illness were the two most common medical problems significantly associated with several unmet social needs. CONCLUSION: This study provides support for the preemptive identification and appropriate management of physical, mental, and social care to improve disproportionate disparities in long-term health outcomes.


Assuntos
Sistema Cardiovascular , Saúde Pública , Humanos , Feminino , Masculino , Criança , Instituições de Assistência Ambulatorial , Cuidado da Criança , Saúde da Criança
5.
Stem Cell Reports ; 18(7): 1405-1420, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37295424

RESUMO

Sarcomeres are fundamental to cardiac muscle contraction. Their impairment can elicit cardiomyopathies, leading causes of death worldwide. However, the molecular mechanism underlying sarcomere assembly remains obscure. We used human embryonic stem cell (hESC)-derived cardiomyocytes (CMs) to reveal stepwise spatiotemporal regulation of core cardiac myofibrillogenesis-associated proteins. We found that the molecular chaperone UNC45B is highly co-expressed with KINDLIN2 (KIND2), a marker of protocostameres, and later its distribution overlaps with that of muscle myosin MYH6. UNC45B-knockout CMs display essentially no contractility. Our phenotypic analyses further reveal that (1) binding of Z line anchor protein ACTN2 to protocostameres is perturbed because of impaired protocostamere formation, resulting in ACTN2 accumulation; (2) F-ACTIN polymerization is suppressed; and (3) MYH6 becomes degraded, so it cannot replace non-muscle myosin MYH10. Our mechanistic study demonstrates that UNC45B mediates protocostamere formation by regulating KIND2 expression. Thus, we show that UNC45B modulates cardiac myofibrillogenesis by interacting spatiotemporally with various proteins.


Assuntos
Chaperonas Moleculares , Miosinas , Humanos , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Desenvolvimento Muscular , Miócitos Cardíacos/metabolismo , Miosinas/metabolismo , Sarcômeros/metabolismo
6.
Inflamm Bowel Dis ; 29(10): 1602-1612, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37235748

RESUMO

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease are 2 types of inflammatory bowel disease (IBD), a group of chronic digestive disorders caused by aberrant immune responses to intestinal microbes. Although changes in the composition of immune cell subsets in the context of IBD have been previously described, the interactions and communication among cells are less well understood. Moreover, the precise mechanisms of action underlying many biologic therapies, including the anti-α4ß7 integrin antagonist vedolizumab, remain incompletely understood. Our study aimed to explore possible additional mechanisms through which vedolizumab acts. METHODS: We performed cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) on peripheral blood and colon immune cells derived from patients with ulcerative colitis treated with the anti-α4ß7 integrin antagonist vedolizumab. We applied a previously published computational approach, NicheNet, to predict immune cell-cell interactions, revealing putative ligand-receptor pairs and key transcriptional changes downstream of these cell-cell communications (CCC). RESULTS: We observed decreased proportions of T helper 17 (TH17) cells in UC patients who responded to vedolizumab and therefore focused the study on identifying cell-cell communications and signals of TH17 cells with other immune cells. For example, we observed that colon TH17 cells from vedolizumab nonresponders were predicted to have a greater degree of interactions with classical monocytes compared with responders, whereas colon TH17 cells from vedolizumab responders exhibited more interactions with myeloid dendritic cells compared with nonresponders. CONCLUSIONS: Overall, our results indicate that efforts to elucidate cell-cell communications among immune and nonimmune cell types may increase the mechanistic understanding of current and investigational therapies for IBD.


Compared to ulcerative patients unresponsive to vedolizumab, immune cell networks of ulcerative colitis patients responsive to vedolizumab have decreased proportion of TH17 and less pro-inflammatory signaling in the gut. Decreased pro-TH17 and interleukin (IL)-1 signaling from classical monocytes and innate immunocytes may mediate this phenotype.


Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Humanos , Colite Ulcerativa/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Integrinas , Comunicação Celular , Fármacos Gastrointestinais/uso terapêutico , Fármacos Gastrointestinais/farmacologia
7.
Appl Opt ; 62(6): A25-A30, 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36821296

RESUMO

Krypton Tagging Velocimetry (KTV) and Picosecond Laser Electronic Excitation Tagging (PLEET) velocimetry at a 100-kHz rate were demonstrated in Mach 18 flow conditions at the Arnold Engineering Development Center (AEDC) Tunnel 9 employing a burst-mode laser system and a custom optical parametric oscillator (OPO). The measured freestream flow velocities from both KTV and PLEET agreed well with the theoretical calculation. The increase in repetition rate provides better capability to perform time-resolved velocimetry measurements in hypersonic flow environments.

8.
Appl Opt ; 62(6): A59-A75, 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36821300

RESUMO

The recent progress in high-speed (≥100k H z) laser diagnostics for hypersonic flows is reviewed. Owing to the ultrahigh flow speed, a laser frequency of 100 kHz or higher is required for hypersonic diagnostics. Here, two main laser diagnostic techniques are discussed: focused laser differential interferometry (FLDI) and pulse-burst laser-based diagnostics. Single- and multiple-point FLDI measurements have been widely applied to hypersonic flows for flow velocity and density fluctuation measurements. The progress of pulse-burst laser-based hypersonic diagnostics, including flow velocity measurements and 2D flow visualization, is also discussed.

9.
Appl Opt ; 62(6): LAC1-LAC3, 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36821332

RESUMO

The eighteenth topical meeting on Laser Applications to Chemical, Security, and Environmental Analysis (LACSEA) was held in Vancouver, Canada from 11-15 July 2022, as part of the Optica Optical Sensors and Sensing Congress in a hybrid format allowing on-site and online attendance. The meeting featured a broad range of distinguished papers focusing on recent advances in laser and optical spectroscopy. A total of 52 contributed and invited papers were presented during the meeting, including topics such as photo-acoustic spectroscopy, imaging, non-linear technologies, frequency combs, remote sensing, environmental monitoring, aerosols, combustion diagnostics, hypersonic flow diagnostics, nuclear diagnostics, fs/ps applications, and machine learning and computational sensing.

10.
Clin Transl Gastroenterol ; 14(5): e00576, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36854061

RESUMO

INTRODUCTION: Crohn's disease (CD) is a major subtype of inflammatory bowel disease (IBD), a spectrum of chronic intestinal disorders caused by dysregulated immune responses to gut microbiota. Although transcriptional and functional changes in a number of immune cell types have been implicated in the pathogenesis of IBD, the cellular interactions and signals that drive these changes have been less well-studied. METHODS: We performed Cellular Indexing of Transcriptomes and Epitopes by sequencing on peripheral blood, colon, and ileal immune cells derived from healthy subjects and patients with CD. We applied a previously published computational approach, NicheNet, to predict immune cell types interacting with CD8 + T-cell subsets, revealing putative ligand-receptor pairs and key transcriptional changes downstream of these cell-cell communications. RESULTS: As a number of recent studies have revealed a potential role for CD8 + T-cell subsets in the pathogenesis of IBD, we focused our analyses on identifying the interactions of CD8 + T-cell subsets with other immune cells in the intestinal tissue microenvironment. We identified ligands and signaling pathways that have implicated in IBD, such as interleukin-1ß, supporting the validity of the approach, along with unexpected ligands, such as granzyme B, which may play previously unappreciated roles in IBD. DISCUSSION: Overall, these findings suggest that future efforts focused on elucidating cell-cell communications among immune and nonimmune cell types may further our understanding of IBD pathogenesis.


Assuntos
Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Ligantes , Doenças Inflamatórias Intestinais/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Comunicação Celular
11.
J Public Health Dent ; 83(1): 87-93, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36651134

RESUMO

OBJECTIVES: This study describes the supply of Latino dentists in the United States from 1980 to 2019, as tabulated by the Census. The number of Latino dentists per 100,000 Latino population was compared to the number of non-Hispanic White (NHW) dentists per 100,000 NHW population. These four-decade comparisons were made for the entire country as well as the five states having the largest Latino populations. METHODS: Data from the decennial census and the American Community Survey were used to identify the nationwide population, the number of dentists, and their respective Spanish-language abilities, stratified by race/ethnic group (Latinos and non-Hispanic Whites). RESULTS: In 1980, there were only 18 Latino dentists for every 100,000 Latino population in the entire nation, compared to 70 NHW dentists per 100,000 NHW population. While there was an increase to 21 Latino dentists per 100,000 in 1990, the supply remained virtually the same over this almost 40-year period, ending back at 18 per 100,000 in 2019. In comparison, there were about four times as many non-Hispanic White dentists as Latino dentists. This national discrepancy was also reflected in the five states that were evaluated. Similarly, Latino dentists were far more likely to speak Spanish than NHW dentists at both the national and state levels. CONCLUSIONS: The Latino dentist supply, already inadequate in 1980, has remained virtually unchanged over the past almost 40 years. The authors believe that this deficiency will have profound consequences, and recommend that initiatives be undertaken to increase the number of Latino dentists.


Assuntos
Censos , Odontólogos , Hispânico ou Latino , Humanos , Etnicidade , Idioma , Estados Unidos
12.
Immunity ; 56(1): 207-223.e8, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36580919

RESUMO

Tissue-resident memory CD8+ T (TRM) cells are a subset of memory T cells that play a critical role in limiting early pathogen spread and controlling infection. TRM cells exhibit differences across tissues, but their potential heterogeneity among distinct anatomic compartments within the small intestine and colon has not been well recognized. Here, by analyzing TRM cells from the lamina propria and epithelial compartments of the small intestine and colon, we showed that intestinal TRM cells exhibited distinctive patterns of cytokine and granzyme expression along with substantial transcriptional, epigenetic, and functional heterogeneity. The T-box transcription factor Eomes, which represses TRM cell formation in some tissues, exhibited unexpected context-specific regulatory roles in supporting the maintenance of established TRM cells in the small intestine, but not in the colon. Taken together, these data provide previously unappreciated insights into the heterogeneity and differential requirements for the formation vs. maintenance of intestinal TRM cells.


Assuntos
Linfócitos T CD8-Positivos , Células T de Memória , Linfócitos T CD8-Positivos/metabolismo , Memória Imunológica , Intestino Delgado , Colo
13.
NPJ Digit Med ; 5(1): 166, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36323795

RESUMO

Diabetic kidney disease is the leading cause of end-stage kidney disease worldwide; however, the integration of high-dimensional trans-omics data to predict this diabetic complication is rare. We develop artificial intelligence (AI)-assisted models using machine learning algorithms to identify a biomarker signature that predisposes high risk patients with diabetes mellitus (DM) to diabetic kidney disease based on clinical information, untargeted metabolomics, targeted lipidomics and genome-wide single nucleotide polymorphism (SNP) datasets. This involves 618 individuals who are split into training and testing cohorts of 557 and 61 subjects, respectively. Three models are developed. In model 1, the top 20 features selected by AI give an accuracy rate of 0.83 and an area under curve (AUC) of 0.89 when differentiating DM and non-DM individuals. In model 2, among DM patients, a biomarker signature of 10 AI-selected features gives an accuracy rate of 0.70 and an AUC of 0.76 when identifying subjects at high risk of renal impairment. In model 3, among non-DM patients, a biomarker signature of 25 AI-selected features gives an accuracy rate of 0.82 and an AUC of 0.76 when pinpointing subjects at high risk of chronic kidney disease. In addition, the performance of the three models is rigorously verified using an independent validation cohort. Intriguingly, analysis of the protein-protein interaction network of the genes containing the identified SNPs (RPTOR, CLPTM1L, ALDH1L1, LY6D, PCDH9, B3GNTL1, CDS1, ADCYAP and FAM53A) reveals that, at the molecular level, there seems to be interconnected factors that have an effect on the progression of renal impairment among DM patients. In conclusion, our findings reveal the potential of employing machine learning algorithms to augment traditional methods and our findings suggest what molecular mechanisms may underlie the complex interaction between DM and chronic kidney disease. Moreover, the development of our AI-assisted models will improve precision when diagnosing renal impairment in predisposed patients, both DM and non-DM. Finally, a large prospective cohort study is needed to validate the clinical utility and mechanistic implications of these biomarker signatures.

14.
Int J Mol Sci ; 23(20)2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36293566

RESUMO

Gilbert's syndrome is mainly diagnosed through genetic analysis and is primarily detected through a mutation in the promoter region of the UGT1A1 gene. However, most of the research has been conducted on Caucasian populations. In this study, we studied the Han population in Taiwan to investigate the possibility of other mutations that could cause Gilbert's syndrome. This study comprised a test group of 45 Taiwanese individuals with Gilbert's syndrome and 180 healthy Taiwanese individuals as a control group. We extracted DNA from the blood samples and then used Axiom Genome-Wide TWB 2.0 array plates for genotyping. Out of 302,771 single nucleotide polymorphisms (SNPs) from 225 subjects, we detected 57 SNPs with the most significant shift in allele frequency; 27 SNPs among them were located in the UGT1A region. Most of the detected SNPs highly correlated with each other and are located near the first exon of UGT1A1, UGT1A3, UGT1A6, and UGT1A7. We used these SNPs as an input for the machine learning algorithms and developed prediction models. Our study reveals a good association between the 27 SNPs detected and Gilbert's syndrome. Hence, this study provides a reference for diagnosing Gilbert's syndrome in the Taiwanese population in the future.


Assuntos
Doença de Gilbert , Humanos , Doença de Gilbert/genética , Doença de Gilbert/diagnóstico , Genótipo , Glucuronosiltransferase/genética , Povo Asiático/genética , Mutação , Éxons
15.
Adv Sci (Weinh) ; 9(25): e2201409, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35822667

RESUMO

The quest for rejuvenation and prolonged lifespan through transfusion of young blood has been studied for decades with the hope of unlocking the mystery of the key substance(s) that exists in the circulating blood of juvenile organisms. However, a pivotal mediator has yet been identified. Here, atypical findings are presented that are observed in a knockin mouse model carrying a lysine to arginine substitution at residue 74 of Krüppel-like factor 1 (KLF1/EKLF), the SUMOylation-deficient Klf1K74R/K74R mouse, that displayed significant improvement in geriatric disorders and lifespan extension. Klf1K74R/K74R mice exhibit a marked delay in age-related physical performance decline and disease progression as evidenced by physiological and pathological examinations. Furthermore, the KLF1(K74R) knockin affects a subset of lymphoid lineage cells; the abundance of tumor infiltrating effector CD8+ T cells and NKT cells is increased resulting in antitumor immune enhancement in response to tumor cell administration. Significantly, infusion of hematopoietic stem cells (HSCs) from Klf1K74R/K74R mice extends the lifespan of the wild-type mice. The Klf1K74R/K74R mice appear to be an ideal animal model system for further understanding of the molecular/cellular basis of aging and development of new strategies for antiaging and prevention/treatment of age-related diseases thus extending the healthspan as well as lifespan.


Assuntos
Longevidade , Sumoilação , Animais , Linfócitos T CD8-Positivos , Células-Tronco Hematopoéticas , Longevidade/genética , Camundongos
16.
Appl Opt ; 61(9): 2192-2197, 2022 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-35333233

RESUMO

A 100 kHz krypton (Kr) tagging velocimetry (KTV) technique was demonstrated in a Mach-6 Ludwieg tube using a burst-mode laser-pumped optical parametric oscillator system. The single-beam KTV scheme at 212 nm produced an insufficient signal in this large hypersonic wind tunnel because of its low Kr seeding (≤5%), low static pressure (∼2.5torr), and long working distance (∼1m). To overcome these issues, a new scheme using two excitation beams was developed to enhance KTV performance. A 355 nm laser beam was combined with the 212 nm beam to promote efficient two-photon Kr excitation at 212 nm, and increase the probability of 2 + 1 resonant-enhanced multiphoton ionization by adding a 355 nm beam. A signal enhancement of approximately six times was obtained. Using this two-excitation beam approach, strong long-lasting KTV was successfully demonstrated at a 100 kHz repetition rate in a Mach-6 flow.

17.
Biomedicines ; 10(1)2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-35052795

RESUMO

An increased risk of cardiovascular events was identified in patients with peripheral artery disease (PAD). Clopidogrel is one of the most widely used antiplatelet medications. However, there are heterogeneous outcomes when clopidogrel is used to prevent cardiovascular events in PAD patients. Here, we use an artificial intelligence (AI)-assisted methodology to identify genetic factors potentially involved in the clopidogrel-resistant mechanism, which is currently unclear. Several discoveries can be pinpointed. Firstly, a high proportion (>50%) of clopidogrel resistance was found among diabetic PAD patients in Taiwan. Interestingly, our result suggests that platelet function test-guided antiplatelet therapy appears to reduce the post-interventional occurrence of major adverse cerebrovascular and cardiac events in diabetic PAD patients. Secondly, AI-assisted genome-wide association study of a single-nucleotide polymorphism (SNP) database identified a SNP signature composed of 20 SNPs, which are mapped into 9 protein-coding genes (SLC37A2, IQSEC1, WASHC3, PSD3, BTBD7, GLIS3, PRDM11, LRBA1, and CNR1). Finally, analysis of the protein connectivity map revealed that LRBA, GLIS3, BTBD7, IQSEC1, and PSD3 appear to form a protein interaction network. Intriguingly, the genetic factors seem to pinpoint a pathway related to endocytosis and recycling of P2Y12 receptor, which is the drug target of clopidogrel. Our findings reveal that a combination of AI-assisted discovery of SNP signatures and clinical parameters has the potential to develop an ethnic-specific precision medicine for antiplatelet therapy in diabetic PAD patients.

18.
Circ Res ; 130(1): 112-129, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34816743

RESUMO

BACKGROUND: Mutations in genes encoding sarcomeric proteins lead to failures in sarcomere assembly, the building blocks of contracting muscles, resulting in cardiomyopathies that are a leading cause of morbidity and mortality worldwide. Splicing variants of sarcomeric proteins are crucial at different stages of myofibrillogenesis, accounting for sarcomeric structural integrity. RBM24 (RNA-binding motif protein 24) is known as a tissue-specific splicing regulator that plays an essential role in cardiogenesis. However, it had been unclear if the developmental stage-specific alternative splicing facilitated by RBM24 contributes to sarcomere assembly and cardiogenesis. Our aim is to study the molecular mechanism by which RBM24 regulates cardiogenesis and sarcomere assembly in a temporal-dependent manner. METHODS: We ablated RBM24 from human embryonic stem cells (hESCs) using CRISPR/Cas9 techniques. RESULTS: Although RBM24-/- hESCs still differentiated into sarcomere-hosting cardiomyocytes, they exhibited disrupted sarcomeric structures with punctate Z-lines due to impaired myosin replacement during early myofibrillogenesis. Transcriptomics revealed >4000 genes regulated by RBM24. Among them, core myofibrillogenesis proteins (eg, ACTN2 [α-actinin 2], TTN [titin], and MYH10 [non-muscle myosin IIB]) were misspliced. Consequently, MYH6 (muscle myosin II) cannot replace nonmuscle myosin MYH10, leading to myofibrillogenesis arrest at the early premyofibril stage and causing disrupted sarcomeres. Intriguingly, we found that the ABD (actin-binding domain; encoded by exon 6) of the Z-line anchor protein ACTN2 is predominantly excluded from early cardiac differentiation, whereas it is consistently included in human adult heart. CRISPR/Cas9-mediated deletion of exon 6 from ACTN2 in hESCs, as well as forced expression of full-length ACTN2 in RBM24-/- hESCs, further corroborated that inclusion of exon 6 is critical for sarcomere assembly. Overall, we have demonstrated that RBM24-facilitated inclusion of exon 6 in ACTN2 at distinct stages of cardiac differentiation is evolutionarily conserved and crucial to sarcomere assembly and integrity. CONCLUSIONS: RBM24 acts as a master regulator to modulate the temporal dynamics of core myofibrillogenesis genes and thereby orchestrates sarcomere organization.


Assuntos
Processamento Alternativo , Células-Tronco Embrionárias Humanas/metabolismo , Desenvolvimento Muscular , Miócitos Cardíacos/metabolismo , Proteínas de Ligação a RNA/metabolismo , Actinina/genética , Actinina/metabolismo , Diferenciação Celular , Linhagem Celular , Conectina/genética , Conectina/metabolismo , Células-Tronco Embrionárias Humanas/citologia , Humanos , Miócitos Cardíacos/citologia , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Miosina não Muscular Tipo IIB/genética , Miosina não Muscular Tipo IIB/metabolismo , Proteínas de Ligação a RNA/genética
19.
Acad Med ; 97(3): 398-405, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34524137

RESUMO

PURPOSE: Some progress has been made in gender diversity in undergraduate medical education and the physician workforce, but much remains to be done to improve workforce disparities for women, particularly women from underrepresented populations, such as Latinas. This study examines the current level of representation and demographic characteristics of Latina physicians, including age, language use, nativity, and citizenship status. METHOD: The authors used data from the 2014-2018 U.S. Census Bureau's American Community Survey (ACS) 5-year estimates for their analyses. During the time period covered by this analysis, ACS response rates ranged from 92.0% to 96.7%. The authors included in this study individuals who self-reported their occupation as physician and who self-identified their race/ethnicity as either non-Hispanic White (NHW) or Hispanic/Latino, regardless of race. The authors used person-level sampling weights provided by the ACS to convert the original 1% sample to a 100% enumeration of the population. RESULTS: According to the ACS 2014-2018 5-year estimates, NHW physicians make up 65.8% (660,031/1,002,527) of physicians in the United States. Women comprise 36.1% (361,442) of the total U.S. physician population; however, Hispanic/Latina women comprise only 2.4% (24,411). The female physician population is younger than the male physician population, and Hispanic female physicians are the youngest. Latina physicians are far more likely to speak Spanish at home than NHW physicians. Immigrants make up 40.1% (9,782/24,411) of the Hispanic female physician population, and 12.3% (3,012/24,411) of Hispanic female physicians are not U.S. citizens. CONCLUSIONS: This study suggests that Latina physicians in the United States are younger, more likely to be bilingual and speak Spanish at home, and very underrepresented, compared with NHW female and male physicians. Increasing their share of the U.S. physician workforce would benefit the pursuit of health equity for an ever more diverse population.


Assuntos
Equidade em Saúde , Médicos , Etnicidade , Feminino , Hispânico ou Latino , Humanos , Masculino , Estados Unidos , Recursos Humanos
20.
Opt Lett ; 46(21): 5489-5492, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34724508

RESUMO

A burst-mode nitrogen (N2) picosecond vibrational coherent anti-Stokes Raman scattering (ps-VCARS) system is presented for accurate flame thermometry at 100 kHz repetition rate. A frequency-tripled ps burst-mode laser is used to pump a custom optical parametric generator/amplifier to produce 607 nm broadband Stokes pulses with 120cm-1 bandwidth, along with a narrowband 532 nm pump/probe beam. A simultaneous shot-to-shot nonresonant background (NRB) measurement is implemented to account for Stokes spectral profile and beam overlap fluctuations. The 100 kHz ps-VCARS data are benchmarked in a near-adiabatic CH4/air Hencken calibration flame with an accuracy of 1.5% and precision of 4.7% up to peak flame temperatures. The use of N2 VCARS and simultaneous NRB measurements enables high-speed thermometry for a wide range of fuels and combustion applications.

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