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1.
Vaccine ; 42(3): 455-463, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38184392

RESUMEN

BACKGROUND: Misinformation presents a critical concern for academic and public health discourse, particularly around vaccine response. Before the COVID-19 pandemic, vaccine hesitancy was responsible for decreased immunization uptake for vaccine-preventable diseases. Misinformation connected to the novel COVID-19 vaccine has further fueled vaccine hesitancy in Colorado and the United States. Our study brings together three different perspectives - physicians, public health professionals, and parents - to understand the impact of misinformation on vaccine uptake in Colorado. Our study proposes a framework for combining the Health Belief Model with the Socio-Ecological model to account for societal factors in healthcare decision making. METHODS: Semi-structured interviews and focus groups with public health professionals, physicians, and parents (n = 31) were conducted in late spring and summer 2022. Data were coded inductively using thematic analysis. Identified themes were deductively categorized according to the Socio-Ecological Model and Health Belief Model. RESULTS: Using a theoretical framework that combined the Health Belief Model and the Socio-Ecological Model, we identified seven factors that influenced vaccine hesitancy in Colorado. Intrapersonal factors included routine vaccine hesitancy connected to perceptions of severity and susceptibility, efficacy, and benefits and barriers to vaccine uptake; interpersonal factors included social networks; institutional factors included mass mediated platforms, portrayals of uncertainty, distrust in institutional sources of information, and political influences in vaccine decision making; and structural factors included economic barriers behind vaccine hesitancy. CONCLUSIONS: Our study provides a unique, triangulated, post-positivist perspective on the role of misinformation in vaccine hesitancy in Colorado. The findings provide evidence that misinformation is an important barrier to vaccination uptake and can permeate multiple socio-ecological determinants/characteristics to influence vaccination behaviors including intrapersonal, interpersonal, institutional, and structural levels. We introduce the Social Ecology of Health Beliefs and Misinformation Framework to account for how misinformation may interrupt vaccine uptake.


Asunto(s)
Vacunas contra la COVID-19 , Vacunas , Humanos , Pandemias , Factores Sociológicos , Vacunación , Red Social , Medio Social
2.
J Microbiol Biol Educ ; 24(3)2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38107997

RESUMEN

In university STEM classrooms, the incorporation of inclusive practices improves student performance, decreases disparities in the academic success of underrepresented students, and increases student retention and persistence in Science, Technology, Engineering, and Mathematics (STEM) programs. Inclusive pedagogical practices include effective instructional choices like active learning, providing rubrics, and other strategies that have been shown to support students from disadvantaged backgrounds. Additionally, explicitly inclusive practices such as addressing microaggressions and sharing pronouns can promote a sense of belonging for students. While a plethora of literature has shown these impacts and faculty have access to resources and training about inclusive pedagogy, we were interested in whether students are noticing these practices and how student identities impact their observations of instructional practices. We surveyed undergraduates (n = 74) from diverse STEM disciplines at a large land-grant university regarding their observation of 11 different inclusive pedagogical practices. Overall, students observed inclusive instructional practices more often than they observed explicitly diversity, equity, and inclusion (DEI)-related practices. For explicitly DEI-related practices, white students observed more practices than Students of Color. This suggests that more work needs to be done to train faculty in explicit DEI-related practices, especially with the goal of supporting Students of Color who have been historically excluded from STEM.

3.
Med Teach ; 45(11): 1224-1227, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37789636

RESUMEN

What is the educational challenge?Medical schools invest significant resources into the creation of multiple-choice items for assessments. This process is costly and requires faculty training. Recently ChatGPT has been used in various areas to improve content creation efficiency, and it has otherwise been used to answer USMLE-style assessment items.What are the proposed solutions?We proposed the use of ChatGPT to create initial drafts of multiple-choice items.What are the potential benefits to a wider global audience?The use of ChatGPT to generate assessment items can decrease resources required, allowing for the creation of more items, and freeing-up faculty time to perform higher level assessment activities. ChatGPT is also able to consistently produce items using a standard format while adhering to item writing guidelines, which can be very challenging for faculty teams.What are the next steps?We plan to pilot ChatGPT drafted questions and compare item statistics for those written by ChatGPT with those written by our content experts. We also plan to further identify the types of questions that ChatGPT is most appropriate for, and incorporate media into assessment items (e.g. images, videos).


Asunto(s)
Docentes , Facultades de Medicina , Humanos , Escolaridad , Grabación de Cinta de Video , Escritura
4.
J Microbiol Biol Educ ; 24(2)2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37614885

RESUMEN

The subject of scientific literacy has never been more critical to the scientific community as well as society in general. As opportunities to spread misinformation increase with the rise of new technologies, it is critical for society to have at its disposal the means for ensuring that its citizens possess the basic scientific literacy necessary to make critical decisions on topics like climate change, biotechnology, and other science-based issues. As the Guest Editors of this themed issue of the Journal of Microbiology and Biology Education, we present a wide array of techniques that the scientific community is using to promote scientific literacy in both academic and nonacademic settings. The diversity of the techniques presented here give us confidence that the scientific community will rise to the challenge of ensuring that our society will be prepared to make fact-based and wise decisions that will preserve and improve our quality of life.

5.
PLoS One ; 18(8): e0287870, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37531388

RESUMEN

This paper investigates the relationship between scientists' communication experience and attitudes towards misinformation and their intention to correct misinformation. Specifically, the study focuses on two correction strategies: source-based correction and relational approaches. Source-based approaches combatting misinformation prioritize sharing accurate information from trustworthy sources to encourage audiences to trust reliable information over false information. On the other hand, relational approaches give priority to developing relationships or promoting dialogue as a means of addressing misinformation. In this study, we surveyed 416 scientists from U.S. land-grant universities using a self-report questionnaire. We find that scientists' engagement in science communication activities is positively related to their intention to correct misinformation using both strategies. Moreover, the scientists' attitude towards misinformation mediates the relationship between engagement in communication activities and intention to correct misinformation. The study also finds that the deficit model perception-that is, the assumption that scientists only need to transmit scientific knowledge to an ignorant public in order to increase understanding and support for science-moderates the indirect effect of engagement in science communication activities on behavioral intention to correct misinformation using relational strategies through attitude towards misinformation. Thus, the deficit model perception is a barrier to engaging in relational strategies to correct misinformation. We suggest that addressing the deficit model perception and providing science communication training that promotes inclusive worldviews and relational approaches would increase scientists' behavioral intentions to address misinformation. The study concludes that scientists should recognize their dual positionality as scientists and members of their community and engage in respectful conversations with community members about science.


Asunto(s)
Comunicación , Intención , Humanos , Actitud , Confianza , Percepción
6.
J Appl Physiol (1985) ; 134(6): 1520-1529, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37167262

RESUMEN

Skeletal muscles bulge when they contract. These three-dimensional shape changes, coupled with fiber rotation, influence a muscle's mechanical performance by uncoupling fiber velocity from muscle belly velocity (i.e., gearing). Muscle shape change and gearing are likely mediated by the interaction between internal muscle properties and contractile forces. Muscles with greater stiffness and intermuscular fat, due to aging or disuse, may limit a muscle's ability to bulge in width, subsequently causing higher gearing. The aim of this study was to determine the influence of internal muscle properties on shape change, fiber rotation, and gearing in the medial (MG) and lateral gastrocnemii (LG) during isometric plantar flexion contractions. Multimodal imaging techniques were used to measure muscle shear modulus, intramuscular fat, and fat-corrected physiological cross-sectional area (PCSA) at rest, as well as synchronous muscle architecture changes during submaximal and maximal contractions in the MG and LG of 20 young (24 ± 3 yr) and 13 older (70 ± 4 yr) participants. Fat-corrected PCSA was positively associated with fiber rotation, gearing, and changes in thickness during submaximal contractions, but it was negatively associated with changes in thickness at maximal contractions. Muscle stiffness and intramuscular fat were related to muscle bulging and reduced fiber rotation, respectively, but only at high forces. Furthermore, the MG and LG had varied internal muscle properties, which may relate to the differing shape changes, fiber rotations, and gearing behaviors observed at each contraction level. These results indicate that internal muscle properties may play an important role in mediating in vivo muscle shape change and gearing, especially during high-force contractions.NEW & NOTEWORTHY Here, we measured internal muscle properties in vivo to determine their influence on the varying shape change and gearing behaviors in the synergistic gastrocnemii muscles. These relationships have previously only been hypothesized or examined within isolated muscles during supramaximal contractions. Our results contribute to a more comprehensive understanding of the factors that influence a muscle's mechanical response to force with implications for preventing or treating muscle deficits associated with aging, disease, and disuse.


Asunto(s)
Contracción Muscular , Músculo Esquelético , Humanos , Músculo Esquelético/fisiología , Contracción Muscular/fisiología , Fenómenos Mecánicos , Contracción Isométrica/fisiología , Envejecimiento/fisiología
7.
J Microbiol Biol Educ ; 24(1)2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37089213

RESUMEN

While numerous studies have examined how scientists perceive doing public communication and engagement, there is limited research on undergraduate science, technology, engineering, and math (STEM) student attitudes toward these meaningful activities. Undergraduate students are more diverse than STEM faculty and may serve as boundary spanners in communities, so exploring their motivations and behaviors in STEM engagement is valuable. For scientists, confidence in communication skills is one driver of public engagement behavior. In this study, we utilized a survey to examine how undergraduate STEM students' science communication skills as well as their science identity and science self-efficacy may drive motivation and behaviors in STEM community engagement. Our findings revealed that STEM students are motivated to do community engagement but lack opportunities to actually do these behaviors. Regression analyses revealed that year in academic progression did not increase STEM students' attitudes and behaviors in community engagement. However, science communication skills, science identity, and science self-efficacy were all predictors of student motivation and behaviors in STEM community engagement. These findings suggest that universities should intentionally provide training in science communication, continue providing support for students developing science identity and self-efficacy, and develop opportunities for undergraduate STEM students to do science outreach and engagement activities.

8.
J Microbiol Biol Educ ; 24(1)2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37089239

RESUMEN

Training in career preparation is vital for biomedical science, microbiology, and related life science undergraduates to know the types of careers available in the field, to obtain employment after graduation, and to be successful in these careers. This is especially critical for historically marginalized students who have lower science, technology, engineering, and math (STEM) retention and lower STEM employment rates. Thus, we developed a career preparation course aimed for second- and third-year students in biomedical science, microbiology, biology, and related majors. This course introduced students to diverse careers via guest speakers and provided training and practice in key career skills, like writing CVs and cover letters. In this curriculum article, we present our course curriculum and resources, evidence of student achievement of learning objectives, and evidence that this course supported growth in constructs like science networking and confidence in future self, which are known to support student STEM retention and success.

9.
CBE Life Sci Educ ; 22(1): ar8, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36637377

RESUMEN

There has been an increased push for science, technology, engineering, and mathematics (STEM) students and scientists to be trained in science communication. Science communication researchers have outlined various models of how scientists interact with nonscientists-including deficit, dialogue, and inclusive approaches. We wanted to analyze whether published science communication curricula for STEM students and scientists exhibit features of inclusive science communication. We analyzed n = 81 published science communication trainings. We found an increase in such publications over the past two decades. We coded the trainings according to the science communication model they most closely follow, finding 40.7% deficit, 39.5% dialogue, and 19.8% inclusive. Trainings for STEM undergraduates were the least likely to provide training in the inclusive model. Finally, only 27.2% of publications included evaluation of the efficacy of the curriculum using an external scale or framework. These findings present opportunities: while it is positive that there are more published science communication curricula, science education and communication researchers should develop and publish more-inclusive science communication trainings for STEM students. Additionally, undergraduate students can and should begin their training in science communication with a focus on inclusivity not deficits. Finally, science education researchers should develop more standards for evaluating the efficacy of inclusive science communication training.


Asunto(s)
Ciencia , Estudiantes , Humanos , Ciencia/educación , Ingeniería/educación , Tecnología/educación , Curriculum , Comunicación , Matemática
10.
Genes (Basel) ; 13(4)2022 04 11.
Artículo en Inglés | MEDLINE | ID: mdl-35456479

RESUMEN

Inappropriate repair of DNA double-strand breaks (DSBs) leads to genomic instability, cell death, or malignant transformation. Cells minimize these detrimental effects by selectively activating suitable DSB repair pathways in accordance with their underlying cellular context. Here, we report that hMSH5 down-regulates NHEJ and restricts the extent of DSB end processing before rejoining, thereby reducing "excessive" deletions and insertions at repair joints. RNAi-mediated knockdown of hMSH5 led to large nucleotide deletions and longer insertions at the repair joints, while at the same time reducing the average length of microhomology (MH) at repair joints. Conversely, hMSH5 overexpression reduced end-joining activity and increased RPA foci formation (i.e., more stable ssDNA at DSB ends). Furthermore, silencing of hMSH5 delayed 53BP1 chromatin spreading, leading to increased end resection at DSB ends.


Asunto(s)
Reparación del ADN por Unión de Extremidades , Nucleótidos , Cromatina , Roturas del ADN de Doble Cadena , ADN de Cadena Simple
11.
J Biomech ; 135: 111033, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35276511

RESUMEN

The study of muscle coordination requires knowledge of the force produced by individual muscles, which can be estimated using Hill-type models. Predicted forces from Hill-type models are sensitive to the muscle's maximal force-generating capacity (Fmax), however, to our knowledge, no study has investigated the effect of different Fmax personalization methods on predicted muscle forces. The aim of this study was to determine the influence of two personalization methods on predicted force-sharing strategies between the human gastrocnemii during walking. Twelve participants performed a walking protocol where we estimated muscle activation using surface electromyography and fascicle length, velocity, and pennation angle using B-mode ultrasound to inform the Hill-type model. Fmax was determined using either a scaling method or experimental method. The scaling method used anthropometric scaling to determine both muscle volume and fiber length, which were used to estimate the Fmax of the gastrocnemius medialis and lateralis. The experimental method used muscle volume and fascicle length obtained from magnetic resonance imaging and diffusion tensor imaging, respectively. We found that the scaling and the experimental method predicted similar gastrocnemii force-sharing strategies at the group level (mean over the participants). However, substantial differences between methods in predicted force-sharing strategies was apparent for some participants revealing the limited ability of the scaling method to predict force-sharing strategies at the level of individual participants. Further personalization of muscle models using in vivo experimental data from imaging techniques is therefore likely important when using force predictions to inform the diagnosis and management of neurological and orthopedic conditions.


Asunto(s)
Imagen de Difusión Tensora , Músculo Esquelético , Electromiografía , Humanos , Contracción Muscular/fisiología , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/fisiología , Ultrasonografía , Caminata/fisiología
12.
J Anat ; 240(1): 131-144, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34411299

RESUMEN

Assessment of regional muscle architecture is primarily done through the study of animals, human cadavers, or using b-mode ultrasound imaging. However, there remain several limitations to how well such measurements represent in vivo human whole muscle architecture. In this study, we developed an approach using diffusion tensor imaging and magnetic resonance imaging to quantify muscle fibre lengths in different muscle regions along a muscle's length and width. We first tested the between-day reliability of regional measurements of fibre lengths in the medial (MG) and lateral gastrocnemius (LG) and found good reliability for these measurements (intraclass correlation coefficient [ICC] = 0.79 and ICC = 0.84, respectively). We then applied this approach to a group of 32 participants including males (n = 18), females (n = 14), young (24 ± 4 years) and older (70 ± 2 years) adults. We assessed the differences in regional muscle fibre lengths between different muscle regions and between individuals. Additionally, we compared regional muscle fibre lengths between sexes, age groups, and muscles. We found substantial variability in fibre lengths between different regions within the same muscle and between the MG and the LG across individuals. At the group level, we found no difference in mean muscle fibre length between males and females, nor between young and older adults, or between the MG and the LG. The high variability in muscle fibre lengths between different regions within the same muscle, possibly expands the functional versatility of the muscle for different task requirements. The high variability between individuals supports the use of subject-specific measurements of muscle fibre lengths when evaluating muscle function.


Asunto(s)
Imagen de Difusión Tensora , Músculo Esquelético , Animales , Imagen de Difusión Tensora/métodos , Femenino , Imagen por Resonancia Magnética , Masculino , Fibras Musculares Esqueléticas , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/fisiología , Reproducibilidad de los Resultados
13.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 7605-7608, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34892850

RESUMEN

The ability to assess balance is essential to determine a patients ability to mitigate any risk of falling. While current assessment tools exist, they either have limitations in that there is no quantitative data recorded, or that they are impractical for general use in clinical settings. In this work, we aim at assessing balance using single-camera videos. In particular, the proposed method uses OpenPose to calculate the Center of Mass and Center of Pressure trajectories. To determine the validity of this approach, estimates obtained in an experimental study were compared to recordings obtained through the use of 3D motion capture and force plate. Our results indicate that this inexpensive, easy to use, and portable alternative has the potential to act as a suitable replacement to assess balance in clinical settings.


Asunto(s)
Fenómenos Biomecánicos , Humanos , Movimiento (Física) , Rango del Movimiento Articular
14.
J Microbiol Biol Educ ; 22(3)2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34970390

RESUMEN

It is critical for science, technology, engineering, and mathematics (STEM) students to develop competencies in science communication, including science writing. However, it can be difficult for instructors and departments to assess the quality of their students' science writing. Many published science writing rubrics are specific to certain genres like lab reports. We thus developed a Universal Science Writing Rubric (USWR) that is usable regardless of the genre or audience of science writing. This tool enables students, instructors, and departments to assess science writing written to lay or scientific audiences, focusing on important rhetorical concerns like science content and interpretation rather than simply surface features like grammar. We demonstrate the use of our USWR on various life science lab reports, scientific review articles, grant proposals, and news articles, showing that the USWR is sensitive enough to highlight statistically significant differences between groups of student writing samples and valid enough to produce results that echo published and anecdotal observations of STEM student science writing skills. Thus, the USWR is a useful tool for assessment of STEM student science writing that is widely applicable in the classroom and laboratory.

15.
J Biomech ; 129: 110823, 2021 12 02.
Artículo en Inglés | MEDLINE | ID: mdl-34736086

RESUMEN

When muscles contract and change length, they also bulge in thickness and/or width. These shape changes extend the functional range of skeletal muscle by allowing individual muscle fibres to shorten at different velocities than the whole muscle. Age-related differences in muscle architecture and tissue properties influence how older muscles change shape and architecture during contractions, yet this remains unexplored in active older adults. The aim of this study was to quantify and compare in vivo muscle architecture and shape changes in the medial (MG) and lateral (LG) gastrocnemii of active younger and older adults during isometric plantarflexion contractions. Fifteen younger (21 ±â€¯2y) and 15 older (70 ±â€¯3y) participants performed contractions at 20%, 40%, 60%, 80%, and 100% of maximum voluntary contraction (MVC). B-mode ultrasound was used to measure fascicle length, pennation angle and muscle thickness in MG and LG. We found no influence of age on changes in normalized fascicle length and thickness, or absolute change in pennation angle during contractions. With increasing contraction level, MG and LG fascicle shortening (P < 0.001) and rotation (P < 0.001) increased. However, the change in muscle thickness increased at higher contraction levels in LG, and not MG. Similarly, increased changes in pennation angle were associated with increased muscle thickness in LG, but not MG at 80% and 100% MVC. These results suggest that (1) gastrocnemii shape changes are similar in active older and younger adults at matched levels of effort, and (2) the relationship between pennation angle and muscle thickness can differ between synergistics (LG and MG) and across contraction levels.


Asunto(s)
Contracción Isométrica , Músculo Esquelético , Anciano , Humanos , Contracción Muscular , Fibras Musculares Esqueléticas , Músculo Esquelético/diagnóstico por imagen , Rotación , Ultrasonografía
16.
Exp Gerontol ; 156: 111594, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34673171

RESUMEN

With aging comes reductions in the quality and size of skeletal muscle. These changes influence the force-generating capacity of skeletal muscle and contribute to movement deficits that accompany aging. Although declines in strength remain a significant barrier to mobility in older adults, the association between age-related changes in muscle structure and function remain unresolved. In this study, we compared age-related differences in (i) muscle volume and architecture, (ii) the quantity and distribution of intramuscular fat, and (iii) muscle shear modulus (an index of stiffness) in the triceps surae in 21 younger (24.6 ± 4.3 years) and 15 older (70.4 ± 2.4 years) healthy adults. Additionally, we explored the relationship between muscle volume, architecture, intramuscular fat and ankle plantar flexion strength in young and older adults. Magnetic resonance imaging was used to determine muscle volume and intramuscular fat content. B-mode ultrasound was used to quantify muscle architecture, shear-wave elastography was used to measure shear modulus, and ankle strength was measured during maximal isometric plantar flexion contractions. We found that older adults displayed higher levels of intramuscular fat yet similar muscle volumes in the medial (MG) and lateral gastrocnemius (LG) and soleus, compared to younger adults. These age-related higher levels of intramuscular fat were associated with lower muscle shear modulus in the LG and MG. We also found that muscle physiological cross-sectional area (PCSA) that accounted for age-associated differences in intramuscular fat showed a modest increase in its association with ankle strength compared to PCSA that did not account for fat content. This highlights that skeletal muscle fat infiltration plays a role in age-related strength deficits, but does not fully explain the age-related loss in muscle strength, suggesting that other factors play a more significant role.


Asunto(s)
Contracción Isométrica , Músculo Esquelético , Anciano , Articulación del Tobillo/fisiología , Humanos , Contracción Isométrica/fisiología , Pierna , Fuerza Muscular/fisiología , Músculo Esquelético/fisiología
17.
J Exp Biol ; 224(12)2021 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-34096594

RESUMEN

The functional difference between the medial gastrocnemius (MG) and lateral gastrocnemius (LG) during walking in humans has not yet been fully established. Although evidence highlights that the MG is activated more than the LG, the link with potential differences in mechanical behavior between these muscles remains unknown. In this study, we aimed to determine whether differences in activation between the MG and LG translate into different fascicle behavior during walking. Fifteen participants walked at their preferred speed under two conditions: 0% and 10% incline treadmill grade. We used surface electromyography and B-mode ultrasound to estimate muscle activation and fascicle dynamics in the MG and LG. We observed a higher normalized activation in the MG than in the LG during stance, which did not translate into greater MG normalized fascicle shortening. However, we observed significantly less normalized fascicle lengthening in the MG than in the LG during early stance, which matched with the timing of differences in activation between muscles. This resulted in more isometric behavior of the MG, which likely influences the muscle-tendon interaction and enhances the catapult-like mechanism in the MG compared with the LG. Nevertheless, this interplay between muscle activation and fascicle behavior, evident at the group level, was not observed at the individual level, as revealed by the lack of correlation between the MG-LG differences in activation and MG-LG differences in fascicle behavior. The MG and LG are often considered as equivalent muscles but the neuromechanical differences between them suggest that they may have distinct functional roles during locomotion.


Asunto(s)
Músculo Esquelético , Caminata , Fenómenos Biomecánicos , Electromiografía , Humanos , Contracción Muscular , Tendones
18.
Artículo en Inglés | MEDLINE | ID: mdl-33584945

RESUMEN

Strong communication skills are essential for future science professionals, but practical training has not been featured strongly in undergraduate curricula. To better train diverse life science majors in communication theory and skills, we created a foundational 200-level course and an advanced 400-level science communication course. Here, we outline the strategy, including lesson plans, assignments, and grading rubrics, for these courses. The science communication assignments presented are diverse in terms of audience, including communication to fellow scientists, to clinicians, and to the public, as well as in terms of format, including written, oral, and visual modes. We also provide suggestions for placing assignments designed to build upon each other into preexisting courses in a scaffolded manner to promote mastery of science communication skills.

19.
Reproduction ; 159(6): 707-717, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32191914

RESUMEN

We previously demonstrated that 5'-AMP-activated protein kinase (AMPK) is essential for normal reproductive functions in female mice. Conditional ablation of Prkaa1 and Prkaa2, genes that encode the α1 and α2 catalytic domains of AMPK, resulted in early reproductive senescence, faulty artificial decidualization, uterine inflammation and fibrotic postparturient endometrial regeneration. We also noted a delay in the timing of embryo implantation in Prkaa1/2d/d female mice, suggesting a role for AMPK in establishing uterine receptivity. As outlined in new studies here, conditional uterine ablation of Prkaa1/2 led to an increase in ESR1 in the uteri of Prkaa1/2d/d mice, resulting in prolonged epithelial cell proliferation and retention of E2-induced gene expression (e.g. Msx1, Muc1, Ltf) through the implantation window. Within the stromal compartment, stromal cell proliferation was reduced by five-fold in Prkaa1/2d/d mice, and this was accompanied by a significant decrease in cell cycle regulatory genes and aberrant expression of decidualization marker genes such as Hand2, Bmp2, Fst and Inhbb. This phenotype is consistent with our prior study, demonstrating a failure of the Prkaa1/2d/d uterus to undergo decidualization. Despite these uterine defects, ovarian function seemed to be normal following ablation of Prkaa1/2 from peri-ovulatory follicles in which ovulation, luteinization and serum progesterone levels were not different on day 5 of pregnancy or pseudopregnancy between Prkaa1/2fl/fl and Prkaa1/2d/d mice. These cumulative findings demonstrate that AMPK activity plays a prominent role in mediating several steroid hormone-dependent events such as epithelial cell proliferation, uterine receptivity and decidualization as pregnancy is established.


Asunto(s)
Proteínas Quinasas Activadas por AMP/genética , Implantación del Embrión/fisiología , Estradiol/farmacología , Receptor alfa de Estrógeno/metabolismo , Útero/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Implantación del Embrión/efectos de los fármacos , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Femenino , Ratones , Ratones Noqueados , Células del Estroma/citología , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismo , Útero/citología , Útero/efectos de los fármacos
20.
Biol Reprod ; 100(6): 1571-1580, 2019 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-30877763

RESUMEN

Progesterone receptor membrane component 1 (PGRMC1) interacts with PGRMC2, and disrupting this interaction in spontaneously immortalized granulosa cells (SIGCS) leads to an inappropriate entry into the cell cycle, mitotic arrest, and ultimately cell death. The present study revealed that PGRMC1 and PGRMC2 localize to the cytoplasm of murine granulosa cells of nonatretric follicles with their staining intensity being somewhat diminished in granulosa cells of atretic follicles. Compared to controls (Pgrmc1fl/fl), the rate at which granulosa cells entered the cell cycle increased in nonatretic and atretic follicles of mice in which Pgrmc1 was conditionally deleted (Pgrmc1d/d) from granulosa cells. This increased rate of entry into the cell cycle was associated with a ≥ 2-fold increase in follicular atresia and the nuclear localization of nuclear factor-kappa-B transcription factor P65; (NFΚB/p65, or RELA). GTPase activating protein binding protein 2 (G3BP2) binds NFΚB/p65 through an interaction with NFΚB inhibitor alpha (IκBα), thereby maintaining NFΚB/p65's cytoplasmic localization and restricting its transcriptional activity. Since PGRMC1 and PGRMC2 bind G3BP2, studies were designed to assess the functional relationship between PGRMC1, PGRMC2, and NFΚB/p65 in SIGCs. In these studies, disrupting the interaction between PGRMC1 and PGRMC2 increased the nuclear localization of NFΚB/p65, and depleting PGRMC1, PGRMC2, or G3BP2 increased NFΚB transcriptional activity and the progression into the cell cycle. Taken together, these studies suggest that PGRMC1 and 2 regulate granulosa cell cycle entry in follicles by precisely controlling the localization and thereby the transcriptional activity of NFΚB/p65.


Asunto(s)
Membrana Celular/fisiología , Células de la Granulosa/fisiología , Proteínas de la Membrana/metabolismo , Mitosis/fisiología , FN-kappa B/metabolismo , Receptores de Progesterona/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Femenino , Quinasa I-kappa B/genética , Quinasa I-kappa B/metabolismo , Proteínas de la Membrana/química , Proteínas de la Membrana/genética , Ratones , Ratones Noqueados , FN-kappa B/genética , Folículo Ovárico/fisiología , Subunidades de Proteína , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Receptores de Progesterona/química , Receptores de Progesterona/genética
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