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Anderson, J. M.

Publications and source records attributed to Anderson, J. M..

5 recordsLinked to original sources

Gestational psychedelic exposure disrupts brain development and offspring behavior in mice

AbstractClassic serotonergic psychedelics engage 5-HT receptors throughout the nervous system, but how maternal exposure intersects with embryonic brain interfaces is poorly defined. Here we tested in mice whether maternally administered lysergic acid diethylamide (LSD) accesses embryonic cerebrospinal fluid (CSF) and whether embryonic choroid plexus (ChP) - a CSF-secreting epithelium enriched for Htr2c - mounts an acute response. Following a single maternal injection (0.3 mg kg-{superscript 1}, subcutaneous), LSD was detectable in embryonic CSF within 5-15 minutes at E12.5 and E16.5. Thirty minutes after maternal dosing, LSD induced Fos in embryonic ChP across ventricles and was accompanied by rapid apical remodeling and increased embryonic CSF protein. In parallel cohorts, psilocybin, 5-MeO-DMT, and the 5-HT2C agonist WAY-161503 elicited a similar Fos response in ChP. Prenatal LSD exposure during mid-gestation was associated with altered S1 cortical cellularity and projection-neuron subtype marker composition at P8; regimen-dependent effects included male-biased changes in SATB2 and CTIP2 populations after repeated exposure. In adulthood, offspring exhibited modest, male-predominant reductions in prepulse inhibition and increased rotational stereotypy. Together, these data identify embryonic CSF as a rapidly accessible compartment for maternal LSD and support a model in which serotonergic agonists can acutely engage ChP epithelium during cerebral cortical development. SignificancePsychedelic use during pregnancy is increasing, but the speed and extent to which these drugs access the embryonic CNS remain unknown. We show that a single maternal dose of LSD appears in mouse embryonic cerebrospinal fluid within five minutes and provokes an immediate response in the choroid plexus, a serotonin receptor-rich epithelium that regulates CSF composition. Psilocybin, 5-MeO-DMT, and a selective 5-HT2C agonist trigger a similar response. Mid-gestational exposure alters cortical neuron composition in neonates and produces persistent behavioral abnormalities in adult offspring, including stereotypies evident from weaning. These data reveal that maternal serotonergic agonists rapidly access embryonic CSF, acutely activate choroid plexus epithelium, and are associated with lasting changes in cortical composition and offspring behavior.

neuroscience↗

Discovery of an Adaptive Neuroimmune Response Driving Itch and Fast Tick Removal with Implications for Preventing Pathogen Transmission

Acquired tick resistance (ATR) is well characterized in tick-exposed animals, compromising tick fitness through antibody-mediated activation of basophils. Yet, anti-tick vaccines inducing ATR have had limited success. Here, we describe a neuroimmune event preceding ATR that leads to rapid host-mediated tick removal. Tick-sensitized guinea pigs mechanically remove ticks within 3-6 hours via an acquired neuroimmune-induced itch response that correlates with increased dermal expression of itch-associated genes like OSM and skin infiltration by T cells and macrophages, independently of IgG and IgE antibodies. When we expose humans to ticks, a similar immune response is observed. Blocking T cells before tick sensitization prevents immune cell infiltration to bite sites and abrogates scratching and tick removal. This neuroimmune response is independent of Trpv1 as tick-sensitized guinea pigs treated with resiniferatoxin remove ticks effectively. Itch-induced tick removal or IITR offers a novel approach to tick-borne disease prevention through early tick detection and removal.

neuroscience↗

Free-living food intake and repopulation of the gut microbiota after a health-screening colonoscopy

ObjectiveRole of microbiome has been highly studied for its association with various medical conditions. After a colonoscopy, repopulation of colonic microbial load is known to occur, however the quality and timing of natural repopulation has not been investigated after a bowel preparation. Further, no study has documented detailed free-living dietary intakes concurrently with gut microbiome repopulation post-colonoscopy. Here we sought to determine the early pattern of repopulation relative to dietary intake. MethodsHealthy adults (n=15 [4 female/11 male], BMI=27.2{+/-}3.9 kg/m2, age 51.4{+/-}7.2 y) who were scheduled to undergo a screening colonoscopy were recruited from the Gastroenterology Clinic at the University of Missouri. Within two weeks before the colonoscopy (baseline), subjects completed detailed food records for 3 days. Post-colonoscopy, subjects ate their free-living diets and detailed food records were collected on Days 0, 1, 2, 4, 7, 10, and 13. Fecal samples were obtained pre-colonoscopy and on post-colonoscopy Days 3, 5, 8, 11, and 14. Gut microbiome composition was assessed by 16S rRNA amplicon sequencing. ResultsWithin 5 days after the procedure, subjects reported consuming more total daily energy relative to baseline, presumably to make up for the low energy intake that occurred during the bowel-prep. At baseline, fiber intake (21.0{+/-}9.1 g/d) was higher than on the day of the colonoscopy, Day 0 (16.1{+/-}11.2, P=0.0159). Thereafter, daily fiber intake was the same as baseline. Marked intersubject microbiome beta diversity was observed by principal coordinate analysis using weighted and unweighted dissimilarities (P=0.0001, F=15.23, one-way PERMANOVA). Select taxa were depleted acutely post-colonoscopy (e.g., within the phylum Bacillota). Specifically, significant effects of time were observed between baseline and Day 3 fecal samples (pairwise P=0.0013, F=2.9). These changes trended to return to baseline by Day 5 and with subsequent samples, taxa remained similar to baseline when tested using a weighted dissimilarity analysis (Bray-Curtis). ConclusionsThese results quantitatively demonstrate the magnitude of the significant changes in microbial relative abundance and diversity immediately post-colonoscopy. The timing of repopulation aligned with changes in fiber intake after the procedure. These data highlight the importance of nutrition after a screening colonoscopy in reestablishing a healthy microbiome.

microbiology↗

Developing and deploying an integrated workshop curriculum teaching computational skills for reproducible research

Inspired by well-established material and pedagogy provided by The Carpentries (Wilson 2016), we developed a two-day workshop curriculum that teaches introductory R programming for managing, analyzing, plotting and reporting data using packages from the tidyverse (Wickham et al. 2019), the Unix shell, version control with git, and GitHub. While the official Software Carpentry curriculum is comprehensive, we found that it contains too much content for a two-day workshop. We also felt that the independent nature of the lessons left learners confused about how to integrate the newly acquired programming skills in their own work. Thus, we developed a new curriculum that aims to teach novices how to implement reproducible research principles in their own data analysis. The curriculum integrates live coding lessons with individual-level and group-based practice exercises, and also serves as a succinct resource that learners can reference both during and after the workshop. Moreover, it lowers the entry barrier for new instructors as they do not have to develop their own teaching materials or sift through extensive content. We developed this curriculum during a two-day sprint, successfully used it to host a two-day virtual workshop with almost 40 participants, and updated the material based on instructor and learner feedback. We hope that our new curriculum will prove useful to future instructors interested in teaching workshops with similar learning objectives.

scientific communication and education↗

The effect of mentee and mentor gender on scientific productivity of applicants for NIH training fellowships

Several studies have suggested that women in science are less productive than men, and that this gap contributes to their under-representation in the ranks of senior researchers. However, few studies have examined the role of mentoring, and in particular mentor gender, on the productivity of female scientists early in their careers. Such efforts are limited by the difficulties of unambiguously linking mentees to their mentors and measuring the research productivity resulting from those relationships. Here we use our novel author disambiguation solution to investigate the role of self-identified gender in mentorship of 12,932 trainees who either successfully or unsuccessfully applied to the National Institutes of Health for research fellowships between fiscal years 2011 and 2017, applying a multi-dimensional framework to assess productivity. We found that, after normalizing for the funding level of mentors, the productivity of female and male mentees is indistinguishable; it is also independent of the gender of the mentor, other than in measures of clinical impact, where women mentored by women outperform other mentee-mentor dyads.

scientific communication and education↗