Opiate-Induced Neuroplastic Alterations to Dopamine Signaling in the Basolateral Amygdala-Prefrontal Cortical Pathway

Opiate addiction is a chronic disorder with high rates of relapse. The failure to maintain sobriety after prolonged abstinence is believed to be due in part to the persistence of potent memories associated with the drug-taking experience. Activation of these memories by re-exposure to drug-related cues can trigger craving in many individuals. Thus, understanding the neurobiological processes underlying the formation of these memories may provide insight into the persistence of addiction. The mammalian basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) comprise a functionally interconnected circuit that is critical for processing opiate-related associative memories. There is some evidence that chronic opiate exposure results in alterations to the function of dopamine (DA) D1 and D2 receptors and their intracellular targets within the BLA, but critical questions remain in regards to these effects within the BLA-mPFC circuit. For instance, opiate-induced alterations to intra-mPFC DA signaling in the context of associative opiate memories has not yet been explored. Furthermore, the role of the DA D3 receptor has not yet been investigated. Finally, there is little understanding of the temporal dynamics underlying these changes in DAergic signaling. Using behavioural models of associative memory formation (conditioned place preference and conditioned place aversion) paired with analyses of protein expression, we further characterized how chronic opiate exposure results in neuroplastic changes to DA receptor expression and signaling in the BLA-mPFC pathway. Here, we report that chronic opiate exposure results in a series of alterations to D1, D2 and D3 signaling within the BLA-mPFC circuit in the context of both opiate reward and withdrawal aversion memories. Specifically, we highlighted the importance of D2 and CaMKIIα signaling within the mPFC, identified the role of intra-BLA D3-Cdk5-calcineurin signaling in reward and aversion memory formation, and temporally mapped opiate-induced alterations to intra-BLA memory molecules. Together, these results provide a more complete understanding of how opiate exposure profoundly alters DA signaling between the dependent and non-dependent states. Interestingly, we found that many of the changes induced by chronic opiate exposure are not only transient, but may be functionally reversible, thus providing an avenue for future development of pharmacological interventions for opiate addiction

Eco-epidemiological approach to management of tuberculosis in free-ranging and captive wildlife, An

2018 Summer.Includes bibliographical references.Tuberculosis (TB) is a disease of global importance affecting millions of humans, livestock, and wildlife. Control and eventual eradication of TB depends on dedicated management actions for all species. Accurately diagnosing TB can be challenging in wildlife species, for which validated tests may be unavailable or of limited sensitivity or specificity. Managing TB in wildlife poses additional difficulties, requiring considerable time and resources to implement at an appropriately broad scale. Each unique ecosystem where TB occurs requires management interventions designed to meet the area's conservation, ecological, social, and financial needs. In this dissertation, I explored the diagnosis and management of tuberculosis in wildlife in three different settings: free-ranging European badgers (Meles meles) in Ireland, working African elephants (Loxodonta africana) in Zimbabwe, and captive African and Asian elephants (Elephas maximus) in North America. Badgers are a reservoir of bovine TB in Ireland, while captive elephants around the world are at risk of TB from their human handlers. Badgers have historically been managed by culling, but there is a current transitioning to vaccination as the primary management tool. In contrast, captive elephants in high-resource settings are typically treated for TB upon diagnosis, although this option may be limited in low-income countries. The first objective of this research was to assess the impact of environmental factors in management of TB over three different studies. I explored how biotic and abiotic factors influence trapping success of badgers being managed for bovine TB in Ireland. In a second study of badgers, I estimated density of a population undergoing vaccination in relation to environmental variables and prior management history. Underlying badger density is an important driver in the TB disease dynamics between cattle and badgers, and can be used in predictions about and assessment of outcomes under vaccination. Finally, I examined potential risk factors for TB seropositive status in working African elephants in Zimbabwe, and identified unique potential exposures from the environment. The second objective of this dissertation was to study the performance of diagnostic tests in a novel setting and interpret the results in the context of exposures within the ecosystem. This study employed two serological tests, STAT-PAK and DPP, for the first time in working African elephants in a range country. I interpreted the results suggestive of exposure to mycobacteria in some elephants based on possible interactions with the complex community of humans, livestock, wildlife, and mycobacteria. The third objective of this dissertation was to develop recommendations for TB management programs based on surveys, capture data, and consideration of individual, population, and community factors. The results from our badger trapping study in Ireland formed the basis of suggested conditions under which vaccine delivery can be increased, because captures are most likely. We used mark-recapture data to estimate badger density in a vaccination area, which adds an important dimension to the Irish TB management program that includes badgers and cattle. Population density is an important factor in pathogen transmission and estimating density using these methods may be a priority for other wildlife populations being managed for TB. Our study of TB treatment in elephants provided a compilation of empirical data for elephant managers and veterinarians to inform clinical decision making. It also underscores the need for improved diagnostics to more confidently identify when animals are no longer infectious. For working African elephants, we documented other wildlife species with host potential on and around facilities, and considered these as possible sources for mycobacterial transmission. Our management guidelines for TB prevention specifically include measures to reduce direct and indirect contact with potential host species. Management of TB across humans and animal species remains a challenging prospect. A One Health approach that incorporates data and techniques across disciplines to build a complete picture of disease control is ideal for TB in wildlife. I drew from ecology and epidemiology to implement a holistic approach to diagnosing and managing TB in species of conservation concern, provide insight into the challenges of diagnosing and managing TB in free-ranging and captive wildlife, describe the benefits of a transdisciplinary approach, and expose areas in need of further research

Feasibility of Measuring Tobacco Smoke Air Pollution in Homes: Report from a Pilot Study.

Tobacco smoke air pollution (TSAP) measurement may persuade parents to adopt smoke-free homes and thereby reduce harm to children from tobacco smoke in the home. In a pilot study involving 29 smoking families, a Sidepak was used to continuously monitor home PM(2.5) during an 8-h period, Sidepak and/or Dylos monitors provided real-time feedback, and passive nicotine monitors were used to measure home air nicotine for one week. Feedback was provided to participants in the context of motivational interviews. Home PM(2.5) levels recorded by continuous monitoring were not well-accepted by participants because of the noise level. Also, graphs from continuous monitoring showed unexplained peaks, often associated with sources unrelated to indoor smoking, such as cooking, construction, or outdoor sources. This hampered delivery of a persuasive message about the relationship between home smoking and TSAP. By contrast, immediate real-time PM(2.5) feedback (with Sidepak or Dylos monitor) was feasible and provided unambiguous information; the Dylos had the additional advantages of being more economical and quieter. Air nicotine sampling was complicated by the time-lag for feedback and questions regarding shelf-life. Improvement in the science of TSAP measurement in the home environment is needed to encourage and help maintain smoke-free homes and protect vulnerable children. Recent advances in the use of mobile devices for real-time feedback are promising and warrant further development, as do accurate methods for real-time air nicotine air monitoring

Monitoring secondhand tobacco smoke remotely in real-time: A simple low-cost approach

Introduction: Secondhand smoke (SHS) in the home is a serious cause of ill-health, especially for children. SHS indoors can be indirectly measured using particulate matter monitors, and interventions have been developed using feedback from these monitors to encourage smoke-free homes. These interventions often use data that are several days out of date, as the data must be downloaded manually from monitors. It would be advantageous to access this information remotely in real-time to provide faster feedback to intervention participants. Methods: Using off-the-shelf computer components and the Dylos DC1700 air quality monitor, a portable internet-connected monitor was developed that can send data to a server remotely. Four of these monitors were tested in homes in Israel to test the reliability of the connection. Data were downloaded from the monitor’s onboard memory and compared to the data sent to the server. Results: Eight homes were monitored for 4 to 6 days, with a combined total count of 44 days. Less than 1% of data was lost, with no outage lasting longer than 1 hour 45 minutes. There was no significant difference in the mean concentrations measured in homes between mobile-transmitted data and data downloaded directly. Conclusions: This system appears to be a reliable way to monitor remotely home air quality for use in intervention studies, and could potentially have applications in other related research. Laboratories that own Dylos DC1700s may wish to consider converting them to such a system to obtain a cost-effective way of overcoming limitations in the Dylos design

Cohesin cleavage by separase is enhanced by a substrate motif distinct from the cleavage site.

Chromosome segregation begins when the cysteine protease, separase, cleaves the Scc1 subunit of cohesin at the metaphase-to-anaphase transition. Separase is inhibited prior to metaphase by the tightly bound securin protein, which contains a pseudosubstrate motif that blocks the separase active site. To investigate separase substrate specificity and regulation, here we develop a system for producing recombinant, securin-free human separase. Using this enzyme, we identify an LPE motif on the Scc1 substrate that is distinct from the cleavage site and is required for rapid and specific substrate cleavage. Securin also contains a conserved LPE motif, and we provide evidence that this sequence blocks separase engagement of the Scc1 LPE motif. Our results suggest that rapid cohesin cleavage by separase requires a substrate docking interaction outside the active site. This interaction is blocked by securin, providing a second mechanism by which securin inhibits cohesin cleavage

Archeota, Spring/Summer 2022

Archeota is a platform for SJSU iSchool students to contribute to the archival conversation. It is written BY students, FOR students. It provides substantive content on archival concerns and issues and promotes professional development in the field of archival studies. Archeota upholds the core values of the archival profession. Contents: From Ashes to Archive: Photojournalist Elizabeth Sunflower’s Body of Work By Laura Darlington Accessibility in Archival Spaces: Breaking Down Barriers for Archival Workers with Disabilities By Kate Goodwin Queer Zine Archive Project: Building a Community Archive of Living History By Alice Wynne Brewster Kahle’s Vision for the Future of Libraries Interview with the Founder of the Internet Archive By Claire Kelley Text, Prose & RocknRoll Podcast: Preserving the Diverse History of Popular Music By Sharon Kosach Farewell to Our Spring 2022 Graduates Interviews With SAA Student Chapter Leaders A Jew in a Catholic Domain: Internship at Schools of the Sacred Heart San Francisco By Max Rosen Summer Reading Recommendations Time to Curl Up With a Good Book! Past Event Archive SJSU SAA Student Chapter events AY 2021-2022https://scholarworks.sjsu.edu/saasc_archeota/1015/thumbnail.jp

Specification of osteoblast cell fate by canonical Wnt signaling requires Bmp2

Enhanced BMP or canonical Wnt (cWnt) signaling are therapeutic strategies employed to enhance bone formation and fracture repair, but the mechanisms each pathway utilizes to specify cell fate of bone-forming osteoblasts remain poorly understood. Among all BMPs expressed in bone, we find that singular deficiency of Bmp2 blocks the ability of cWnt signaling to specify osteoblasts from limb bud or bone marrow progenitors. When exposed to cWnts, Bmp2-deficient cells fail to progress through the Runx2/Osx1 checkpoint and thus do not upregulate multiple genes controlling mineral metabolism in osteoblasts. Cells lacking Bmp2 after induction of Osx1 differentiate normally in response to cWnts, suggesting that pre-Osx1(+) osteoprogenitors are an essential source and a target of BMP2. Our analysis furthermore reveals Grainyhead-like 3 (Grhl3) as a transcription factor in the osteoblast gene regulatory network induced during bone development and bone repair, which acts upstream of Osx1 in a BMP2-dependent manner. The Runx2/Osx1 transition therefore receives crucial regulatory inputs from BMP2 that are not compensated for by cWnt signaling, and this is mediated at least in part by induction and activation of Grhl3.National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH-NIAMS)Harvard Sch Dent Med, Dept Dev Biol, 188 Longwood Ave, Boston, MA 02115 USASaitama Med Univ, Res Ctr Genom Med, Div Pathophysiol, 1397-1 Yamane, Hidaka, Saitama 3501241, JapanUniv Fed Sao Paulo, Inst Ciencia & Tecnol, Rua Talim 330, BR-12231280 Sao Jose Dos Campos, SP, BrazilUniversidade Federal de São Paulo, Rua Talim, 330, São José dos Campos, São Paulo, CEP 12231-280, BrazilNIH-NIAMS: R01 AR055904Web of Scienc

Matter Couplings and Equivalence Principles for Soft Scalars

Scalar effective field theories with enhanced soft limits behave in many ways like gauge theories and gravity. In particular, symmetries fix the structure of interactions and the tree-level S-matrix in both types of theories. We explore how this analogy persists in the presence of matter by considering theories with additional fields coupled to the Dirac-Born-Infeld (DBI) scalar or the special galileon in a way that is consistent with their symmetries. Using purely on-shell arguments, we show that these theories obey analogues of the S-matrix equivalence principle whereby all matter fields must couple to the DBI scalar or the special galileon through a particular quartic vertex with a universal coupling. These equivalence principles imply the universality of the leading double soft theorems in these theories, which are scalar analogues of Weinberg's gravitational soft theorem, and can be used to rule out interactions with massless higher-spin fields when combined with analogues of the generalized Weinberg-Witten theorem. We verify in several examples that amplitudes with external matter fields nontrivially exhibit enhanced single soft limits and we show that such amplitudes can be constructed using soft recursion relations when they have sufficiently many external DBI or special galileon legs, including amplitudes with massive higher-spin fields. As part of our analysis we construct a recently conjectured special galileon-vector effective field theory.Comment: 43 pages; v2: minor changes, matches the published versio