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C-C Chemokine Receptor 7 (CCR7) mediates T-cell acute lymphoblastic leukemia (T-ALL) invasion of the central nervous system (CNS) mediated by chemotactic migration to C-C chemokine ligand 19 (CCL19). To determine if a CCL19 antagonist, CCL198-83, could inhibit CCR7-induced chemotaxis and signaling via CCL19 but not CCL21, we used transwell migration and Ca2+ mobilization signaling assays. We found that in response to CCL19, human T-ALL cells employ ß2 integrins to invade human brain microvascular endothelial cell monolayers. In vivo, using an inducible mouse model of T-ALL, we found that we were able to increase the survival of the mice treated with CCL198-83 when compared to non-treated controls. Overall, our results describe a targetable cell surface receptor, CCR7, which can be inhibited to prevent ß2-integrin-mediated T-ALL invasion of the CNS and potentially provides a platform for the pharmacological inhibition of T-ALL cell entry into the CNS.
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Antígenos CD18 , Quimiocina CCL19 , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Receptores CCR7 , Receptores CCR7/metabolismo , Receptores CCR7/genética , Animales , Humanos , Ratones , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Quimiocina CCL19/metabolismo , Antígenos CD18/metabolismo , Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/patología , Línea Celular Tumoral , Quimiotaxis/efectos de los fármacos , Quimiocina CCL21/metabolismo , Movimiento Celular/efectos de los fármacos , Invasividad NeoplásicaRESUMEN
Research training is an important intervention for preparing undergraduate students to pursue further studies and develop research skills. Furthermore, there is mounting evidence indicating that mentored research impacts student success metrics. At the University of Texas at El Paso, a Freshman Year Research Intensive Sequence (FYRIS) was developed to prepare first-year students for research experiences. The FYRIS courses combine research foundations and research-intensive courses. In this manuscript, we present findings demonstrating the impact of FYRIS and subsequent mentored research experiences on 4-year retention and graduation. Results suggest that participation in FYRIS and independent mentored research has a large positive impact on 4-year retention and graduation, while other historical socioeconomic variables have minimal to no impact.
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BACKGROUND: The goal of this study was to elucidate the fundamental connectivity-resting-state connectivity-within and between nodes in the olfactory and prosocial (PS) cores, which permits the expression of social monogamy in males; and how differential connectivity accounts for differential expression of prosociality and aggression. METHODS: Using resting-state functional magnetic resonance imaging, we integrated graph theory analysis to compare functional connectivity between two culturally/behaviorally distinct male prairie voles (Microtusochrogaster). RESULTS: Illinois males display significantly higher levels of prosocial behavior and lower levels of aggression than KI (Kansas dam and Illinois sire) males, which are associated with differences in underlying neural mechanisms and brain microarchitecture. Shared connectivity 1) between the anterior hypothalamic area and the paraventricular nucleus and 2) between the medial preoptic area and bed nucleus of the stria terminalis and the nucleus accumbens core suggests essential relationships required for male prosocial behavior. In contrast, Illinois males displayed higher levels of global connectivity and PS intracore connectivity, a greater role for the bed nucleus of the stria terminalis and anterior hypothalamic area, which were degree connectivity hubs, and greater PS and olfactory intercore connectivity. CONCLUSIONS: These findings suggest that behavioral differences are associated with PS core degree of connectivity and postsignal induction. This transgenerational system may serve as powerful mental health and drug abuse translational model in future studies.
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Conducta Sexual Animal , Conducta Social , Animales , Arvicolinae/metabolismo , Encéfalo/metabolismo , Pradera , Humanos , MasculinoRESUMEN
Summer undergraduate research experience (SURE) programs are proven interventions that provide undergraduate students with opportunities to develop research skills under the mentorship of a faculty member. These are essential programs, particularly for members of underrepresented minorities, because SUREs are known to broaden their participation and increase retention. We present the results of a study investigating the influence of faculty mentorship quality on the quality of research presentations for undergraduate students attending a 10-week, distributed, multi-institutional SURE program focused on biomedical research training. Upon returning to the home institution, students presented research posters at a local symposium. Poster presentations were judged using a scale validated as part of this project. Combining collected information on student demographics and their self-reported assessments of research gains and belonging to the scientific community, we made use of data analytics methodologies to appropriately merge and analyze the data to address the overarching research question: What are the independent and combined effects of the quality of faculty mentorship and student characteristics on the quality of SURE student poster presentations? Results show that faculty mentor quality functions as a moderating influence for student characteristics on research presentation quality. Implications and recommendations for SURE program implementation are discussed.
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Investigación Biomédica , Docentes , Mentores , Investigación Biomédica/educación , Humanos , Estudiantes/estadística & datos numéricosRESUMEN
One of the key challenges many peer-to-peer mentoring programs face is the lack of high-quality mentor training. In order to address this issue, the BUILDing SCHOLARS (BUILD) program at The University of Texas at El Paso (UTEP) implements a structured peer mentor training and provides the training to BUILD fellows at UTEP for four academic years. This paper focuses on introducing the BUILD Peer Mentor Training (BPMT) model and investigates its impacts on students using program evaluation data. Our results reveal that BUILD peer mentors were satisfied with the BPMT and their relationships with the mentees. They also reported that the training greatly improved their problem solving and action planning skills, and slightly improved their communication skills and ability to assess a mentee's understanding. Finally, four practical recommendations are provided for institutions and programs that might be interested in implementing a similar peer mentor training.
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Course-based undergraduate research experiences (CUREs) serve to increase student access to authentic scientific opportunities. Current evidence within the literature indicates that engagement in CUREs promotes students' science identity development, science self-efficacy, motivation, and ability to "think like a scientist." Despite the importance of these findings, few studies have examined the behaviors and interactions occurring within CURE and non-CURE settings and the impact of those behaviors on said student outcomes. To address these concerns, we conducted a mixed-methods study to explore student and instructor behaviors in four CURE and four non-CURE introductory biology laboratory sections. Representative video data were collected in each section and coded using the Laboratory Observation Protocol for Undergraduate STEM. In addition, pre/postsemester affective survey data were obtained from CURE and non-CURE participants. Results indicated that CURE students and instructors engaged in more interactive behaviors (e.g., one-on-one dialogue, questioning) than their non-CURE counterparts, a finding confirmed by analyzing behavioral patterns via construction of partial correlation networks. Multiple regression analyses further revealed that both student and instructor interactive behaviors and enrollment in a CURE were strong predictors of pre/postsemester shifts in student motivation, science identity development, collaboration, and perceived opportunities to make relevant scientific discoveries.
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Motivación , Ciencia , Ambiente , Humanos , Laboratorios , Aprendizaje , Ciencia/educación , Estudiantes , UniversidadesRESUMEN
Habitat heterogeneity and local resource distribution play key roles in animal search patterns. Optimal strategies are often considered for foraging organisms, but many of the same predictions are applicable to mate searching. We quantified movement and space use by a pitviper to test whether Native Habitats (NH) and human-made Resource Hotspots (RH) facilitate alternative seasonal spatial strategies as a result of critical resources, including potential mating partners, being widely dispersed in NH and clustered in RH. Independent of habitat category, seasonal patterns resembled an intermediate mating system with elements of prolonged male mate-searching and female-defense. However, individuals using primarily NH or RH exhibited alternative strategies. NH rattlesnakes displayed greater movement and larger home ranges than RH rattlesnakes across behavioral seasons. NH males increased movement distances and home ranges during the mating season, while RH males displayed minimal or no seasonal shifts. NH females also elevated movement distances during the mating season, while RH females showed no significant seasonal differences. Despite contrasting spatial patterns, mating success and female-defense effort were not significantly affected by habitat category. This unique study system highlights the potential for interactions among sexual selection, habitat heterogeneity, and behavioral plasticity to facilitate divergent search tactics within populations.
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Migración Animal , Ecosistema , Ambiente , Preferencia en el Apareamiento Animal , Reproducción , Estaciones del Año , Viperidae/fisiología , Distribución Animal , Animales , Femenino , Geografía , Humanos , Masculino , Análisis EspacialRESUMEN
INTRODUCTION: Lead (Pb) exposure yielding blood lead levels (BLL) as low as 2 µg/dl in children is an international problem. More common in US low-income neighborhoods, childhood Pb exposure can cause behavioral and cognitive deficits, including working memory impairments, which can persist into adulthood. So far, studies characterized short-term effects of high Pb exposure on neuronal structure and function. However, long-term consequences of early chronic Pb exposure on neuronal activity are poorly documented. METHODS: Here, we exposed male and female mice (PND [postnatal day] 0 to PND 28) to one of three Pb treatments: 0 ppm (sodium-treated water, control), 30 ppm (low dose), and 330 ppm (high dose) lead acetate. Once the male and female mice were 9-12 months old, extracellular field recordings on hippocampal slices were performed. RESULTS: We show that at CA3 to CA1 synapses, synaptic transmission was decreased and neuronal fiber activity was increased in males exposed to lowest level Pb. In contrast, both synaptic transmission and neuronal fiber activity were increased in females exposed to high Pb. The ventral hippocampus-medial prefrontal cortex (vHPC-mPFC) synapses are crucial for working memory in rodents. The lowest level Pb decreased vHPC-mPFC synaptic transmission, whereas high Pb decreased short-term synaptic depression. CONCLUSIONS: Overall, we show for the first time that early exposure to either high or lowest level Pb has long-term consequences on different synaptic properties of at least two hippocampal synapses. Such consequences of early Pb exposure might worsen the cognitive decline observed in aging men and women. Our results suggest that additional efforts should focus on the consequences of early Pb exposure especially in at-risk communities.