Que Se Sepa: Perspectives from the Puerto Rican Diaspora in Hartford

Que Se Sepa focuses on the perspectives of individuals of Puerto Rican descent living in the Diaspora here in the city of Hartford, Connecticut. These individuals represent a community that comprises of first, second, and third generation Puerto Ricans. Through discussions surrounding the topics of food, religion, politics, race, language, and music/arts, Que Se Sepa presents an array of perspectives regarding experiences both in Hartford’s Puerto Rican Diaspora and in Puerto Rico. Que Se Sepa is two things: an effort to promote dialogue and a personal journey. Que Se Sepa the dialogue gives direct agency to a community. Within the documentary, the voice of the researcher is taken out which allows 18 individuals featured in the film to directly share their story with an audience. Before embarking on this research project, I profess to knowing relatively little about vibrant community beyond the gates of Trinity College. Que Se Sepa has allowed me to establish a personal connection and appreciation for the individuals living and working within the Hartford community. I hope that both the documentary and written essay ignites a yearning for greater communication and understanding within and outside the city of Hartford

Teacher perspectives on language learning psychology

Research into the psychology of language learning has grown exponentially in the last decade, yet, teacher perspectives on the field have been surprisingly absent from this body of research. The present study was designed to address this gap. Drawing on a survey with 311 foreign language teachers working at different school levels in 3 European countries, and on individual, semi-structured interviews with 11 teachers, the study focuses on the psychological aspects of language learning which teachers felt were particularly important in their own settings. In particular, teachers’ beliefs, experiences and teaching strategies were explored. The data also revealed strong interconnections between language learning psychology constructs, differences across contexts, and a perceived link between learner and teacher psychology

Correction: HUNK phosphorylates EGFR to regulate breast cancer metastasis

Erratum for 10.1038/s41388-019-1046-

A prospective study of hearing changes after beginning zidovudine or didanosine in HIV-1 treatment-naïve people

BACKGROUND: While hearing loss in HIV-infected people after beginning nucleoside reverse transcriptase inhibitors (NRTIs) has been reported, there have been no prospective studies that measured hearing changes longitudinally in treatment-naïve HIV-infected subjects following initiation of regimens containing NRTIs. The goal of this study was to conduct a prospective assessment of the contribution of zidovudine (ZDV) and didanosine (ddI) to hearing loss METHODS/DESIGN: A prospective observational pilot study to determine whether ZDV or ddI, alone or in combination, are associated with sensorineural hearing loss in HIV-infected persons. Changes in hearing levels at all frequencies and in low and high frequency pure tone averages were measured at baseline, 16, and 32 weeks after initiating antiretroviral therapy. DISCUSSION: Treatment with ZDV and ddI did not result in loss of hearing, even after taking into account noise exposure, immune status and age. The results of this prospective pilot study do not support the notion that treatment with nucleoside antiretrovirals damages hearing

Coronaridine congeners attenuate fentanyl seeking during prolonged abstinence

Background: The prevalence of opioid use disorder (OUD) has reached epidemic proportions with a record-breaking number of overdose deaths. Over 70% of the record-breaking number of overdose deaths are caused by synthetic opioids, including fentanyl. Fentanyl is commonly administered intravenously or by inhalation (smoking/vaping), which results in rapid drug bioavailability in the brain. There is a current need to identify a novel pharmacologic therapy to treat OUD, and there is increasing evidence to support the use of novel compounds referred to as coronaridine congeners to treat OUD and other psychiatric illnesses. In preclinical models, coronaridine congeners have been shown to decrease self-administration of drugs of abuse and induce antidepressant and anxiolytic effects. Here we used a preclinical fentanyl vapor self-administration model and fast-scan cyclic voltammetry (FSCV) to study the anti-addictive effects of two coronaridine congeners, 18-methoxycoronaridine (18-MC) and catharanthine (Cath).Methods: C57BL/6J mice were trained to self-administer vaporized fentanyl (5 mg/mL) or vehicle in airtight operant chambers. Mice self-administered vapor for 1 hour per day for 10 days (sessions were conducted for 5 consecutive days, followed by 2 days off). Chambers were equipped with two nosepokes, one active and one inactive. A successful response in the active nosepoke resulted in a vapor delivery that coincided with the presentation of a cue light, followed by a 1-minute timeout period. Mice learned to self-administer vapor with 3-second vapor deliveries for the first 3 days of training, which was then reduced to 1.5-second vapor deliveries the remaining 7 days. After training, mice were returned to their home cages for a forced abstinence period. Cue-induced drug seeking tests were conducted on abstinence days (AD) 20 and 25. During cue-induced seeking tests, successful responses in the active nosepoke resulted in presentation of the drug-associated cue, but no vapor was delivered (i.e. extinction conditions). Cue-induced drug seeking tests were conducted using a crossover design where half of subjects received coronaridine treatment (18-MC or Cath), while the other half received vehicle (ddH2O), on AD20. On AD25, subjects received the opposite treatment compared to AD20. Mice were injected (i.p.) with either vehicle or coronaridine treatment 1 hour before seeking tests. To examine the molecular mechanism of coronaridine congeners, FSCV was conducted on dopaminergic pre-synaptic terminals in the nucleus accumbens (NAc) neurons to measure dopamine (DA) release in the presence of 18-MC and Cath with or without nicotinic acetylcholine receptor antagonists.Results: We found that both 18-MC and Cath significantly reduced fentanylseeking during prolonged abstinence with no effect on mice that had previously self-administered vehicle. Furthermore, FSCV revealed that 18-MC and Cath significantly reduced DA release onto NAc neurons.Conclusion: In this study, we report that both 18-MC and Cath decrease fentanyl seeking during prolonged abstinence. DA release is important for opioid-related behaviors, and we found that 18-MC and Cath reduce DA release in the NAc, a mechanism that may underlie the effect of coronaridine congeners on fentanyl seeking. Together, these results provide evidence that coronaridine congeners may be promising novel compounds for the pharmacotherapeutic treatment of OUD

Identification of Transcription Factors Regulating CTNNAL1 Expression in Human Bronchial Epithelial Cells

Adhesion molecules play important roles in airway hyperresponsiveness or airway inflammation. Our previous study indicated catenin alpha-like 1 (CTNNAL1), an alpha-catenin-related protein, was downregulated in asthma patients and animal model. In this study, we observed that the expression of CTNNAL1 was increased in lung tissue of the ozone-stressed Balb/c mice model and in acute ozone stressed human bronchial epithelial cells (HBEC). In order to identify the possible DNA-binding proteins regulating the transcription of CTNNAL1 gene in HBEC, we designed 8 oligo- nucleotide probes corresponding to various regions of the CTNNAL1 promoter in electrophoretic mobility shift assays (EMSA). We detected 5 putative transcription factors binding sites within CTNNAL1 promoter region that can recruit LEF-1, AP-2α and CREB respectively by EMSA and antibody supershift assay. Chromatin immunoprecipitation (ChIP) assay verified that AP-2 α and LEF-1 could be recruited to the CTNNAL1 promoter. Therefore we further analyzed the functions of putative AP-2 and LEF-1 sites within CTNNAL1 promoter by site-directed mutagenesis of those sites within pGL3/FR/luc. We observed a reduction in human CTNNAL1 promoter activity of mutants of both AP-2α and LEF-1 sites. Pre-treatment with ASOs targeting LEF-1and AP-2α yielded significant reduction of ozone-stress-induced CTNNAL1 expression. The activation of AP-2α and LEF-1, followed by CTNNAL1 expression, showed a correlation during a 16-hour time course. Our data suggest that a robust transcriptional CTNNAL1 up-regulation occurs during acute ozone-induced stress and is mediated at least in part by ozone-induced recruitments of LEF-1 and AP-2α to the human CTNNAL1 promoter

Targeting CXCR4 (CXC Chemokine Receptor Type 4) for Molecular Imaging of Aldosterone-Producing Adenoma

Primary aldosteronism is the most frequent cause of secondary hypertension and is associated with increased morbidity and mortality compared with hypertensive controls. The central diagnostic challenge is the differentiation between bilateral and unilateral disease, which determines treatment options. Bilateral adrenal venous sampling, currently recommended for differential diagnosis, is an invasive procedure with several drawbacks, making it desirable to develop novel noninvasive diagnostic tools. When investigating the expression pattern of chemokine receptors by quantitative real-time polymerase chain reaction and immunohistochemistry, we observed high expression of CXCR4 (CXC chemokine receptor type 4) in aldosterone-producing tissue in normal adrenals, adjacent adrenal cortex from adrenocortical adenomas, and in aldosterone-producing adenomas (APA), correlating strongly with the expression of CYP11B2 (aldosterone synthase). In contrast, CXCR4 was not detected in the majority of nonfunctioning adenomas that are frequently found coincidently. The specific CXCR4 ligand 68Ga-pentixafor has recently been established as radiotracer for molecular imaging of CXCR4 expression and showed strong and specific binding to cryosections of APAs in our study. We further investigated 9 patients with primary aldosteronism because of APA by 68Ga-pentixafor-positron emission tomography. The tracer uptake was significantly higher on the side of increased adrenocortical aldosterone secretion in patients with APAs compared with patients investigated by 68Ga-pentixafor-positron emission tomography for other causes. Molecular imaging of aldosterone-producing tissue by a CXCR4-specific ligand may, therefore, be a highly promising tool for noninvasive characterization of patients with APAs