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Genetically encoded dopamine sensors based on green fluorescent protein (GFP) enable high-resolution imaging of dopamine dynamics in behaving animals. However, these GFP-based variants cannot be readily combined with commonly used optical sensors and actuators, due to spectral overlap. We therefore engineered red-shifted variants of dopamine sensors called RdLight1, based on mApple. RdLight1 can be combined with GFP-based sensors with minimal interference and shows high photostability, permitting prolonged continuous imaging. We demonstrate the utility of RdLight1 for receptor-specific pharmacological analysis in cell culture, simultaneous assessment of dopamine release and cell-type-specific neuronal activity and simultaneous subsecond monitoring of multiple neurotransmitters in freely behaving rats. Dual-color photometry revealed that dopamine release in the nucleus accumbens evoked by reward-predictive cues is accompanied by a rapid suppression of glutamate release. By enabling multiplexed imaging of dopamine with other circuit components in vivo, RdLight1 opens avenues for understanding many aspects of dopamine biology.

This research examines the effectiveness of early intervention on academic success for at-risk students. An intervention program is implemented in a minority serving public university by providing counseling and advising to academically at-risk students. Student performance is monitored and evaluated to explore whether early intervention impacts the likelihood of success for at-risk students. Adopting the matching sample method, our preliminary results show that at-risk students who receive additional advising are more likely to pass the course than those who don't receive such advising. We also find that student's prior GPA and gender have a statistically significant impact on students' eventual academic performance. These results provide further evidence that early intervention strategies can be effective in improving student success.

This paper describes research in progress concerning the development and use of a newly created tool, the Decision-Making Grid, which was designed to teach undergraduate management students to develop and use metacognitive regulation skills to improve decision-making by requiring students to construct improved decision-making models in a boundedly rational manner. When students are required to use the metacognitive skills of planning, monitoring and evaluating focused on important and relevant decision-criteria, students are better positioned to commit to appropriate academic preparation. The null hypothesis proposing that there would be no variance in means in the measure of commitment to academic preparation was rejected using data from three academic years of data. Qualitative analyses provide evidence that the Grid can help students commit to academic preparation.

Introduction: A hallmark of T cell dysregulation during sepsis is the downregulation of costimulatory molecules. CD28 is one of T cell costimulatory molecules significantly altered on memory T cells during sepsis. We recently showed that treatment with a aCD28 agonist in septic immunologically experienced mice led to improved survival. Therefore, here we aimed to identify the cell subset(s) necessary for the survival benefit observed in the context of CD28 agonism, and to further investigate the mechanism by which CD28 agonism improves sepsis survival in immunologically experienced mice. Methods: Mice received specific pathogen inoculation to generate memory T cell populations similar in frequency to that of adult humans. Once these infections were cleared and the T cell response had transitioned to the memory phase, animals were rendered septic via cecal ligation and puncture in the presence or absence of an agonistic anti-CD28 mAb. Results: Results demonstrated that CD8+ T cells, and not bulk CD4+ T cells or CD25+ regulatory T cells, were necessary for the survival benefit observed in CD28 agonist-treated septic immunologically experienced mice. Upon examination of these CD8+ T cells, we found that CD28 agonism in septic immunologically experienced mice was associated with an increase in Foxp3+ CD8+ T cells as compared to vehicle-treated controls. When CD8+ T cells were depleted in septic immunologically experienced mice in the setting of CD28 agonism, a significant increase in levels of inflammatory cytokines in the blood was observed. Discussion: Taken together, these results indicate that CD28 agonism in immunologically experienced mice effectively suppresses inflammation via a CD8+-dependent mechanism to decrease mortality during sepsis. [ABSTRACT FROM AUTHOR]

In this investigation, the authors analyzed the cost effectiveness of receiving passing scores for Black students on Advanced Placement exams in three states (Texas, New York, and Florida) for a 16-year period (e.g., 1997 through 2012). College Board data were downloaded and analyzed for all Advanced Placement exams for Black students in these three states for this time period. Cost effectiveness ratios (i.e., the ratio of passing score costs to failing score costs) were negative for every year for Black students in all three states. As such, a lack of equity was clearly present in the overall Advanced Placement exam performance of Black students in these three states. Given the limited education budgets in many states, it is important for these dollars to be spent wisely. Implications of the findings are discussed, particularly with respect to policy regarding college preparatory programs.

Proximity labeling with genetically encoded enzymes is widely used to study protein–protein interactions in cells. However, the accuracy of proximity labeling is limited by a lack of control over the enzymatic labeling process. Here, we present a light-activated proximity labeling technology for mapping protein–protein interactions at the cell membrane with high accuracy and precision. Our technology, called light-activated BioID (LAB), fuses the two halves of the split-TurboID proximity labeling enzyme to the photodimeric proteins CRY2 and CIB1. We demonstrate, in multiple cell lines, that upon illumination with blue light, CRY2 and CIB1 dimerize, reconstitute split-TurboID and initiate biotinylation. Turning off the light leads to the dissociation of CRY2 and CIB1 and halts biotinylation. We benchmark LAB against the widely used TurboID proximity labeling method by measuring the proteome of E-cadherin, an essential cell–cell adhesion protein. We show that LAB can map E-cadherin-binding partners with higher accuracy and significantly fewer false positives than TurboID. [ABSTRACT FROM AUTHOR]

Preterm pediatric patients with bronchopulmonary dysplasia (BPD) represent a subgroup previously deemed high risk candidates for ECLS (extracorporeal life support) due to suspected high mortality or increased post ECLS morbidity. The aim of this study was to determine outcomes for patients with an established history of BPD who subsequently required ECLS.A single center retrospective review was performed between 01/2010-06/2022 for patients less than 2 years of age, born prematurely (<32 weeks) with a subsequent diagnosis of BPD, and who required ECLS for respiratory failure. Demographic and clinical data, including ECLS data, were collected. Speech, language, feeding/swallowing, cognitive, hearing, vision, or motor function deficits were obtained with a median follow up of 42 months following discharge.Nineteen patients met criteria. The median birth weight and gestational age was 0.86 kg (IQR 0.73, 1.0) and 26 weeks (IQR 25, 27), respectively. The median chronological age at cannulation was 12.1 months. The most common etiologies for respiratory failure requiring ECLS were viral (68.4%) and bacterial (21.1%) pneumonia. Survival to decannulation was 78.9% (15/19) and survival to hospital discharge was 63.2% (12/19). Amongst survivors to discharge, 42% (5/12) required new or additional home oxygen and 50% (6/12) were noted to have neurodevelopmental/behavioral concerns on follow up at 1 year with 25% (3/12) with concerns beyond a year.Patients with underlying BPD who require ECLS have comparable mortality and long-term neurodevelopmental outcomes to non-BPD patients with respiratory failure. This information can be useful when considering ECLS candidacy and providing family counseling. [ABSTRACT FROM AUTHOR]