Predictors of Psychedelic Experience: A Thematic Analysis

Research on the therapeutic potential of psychedelic substances is rapidly expanding. A major limitation within this field is the unpredictability of individual responses to psychedelic substances. A better understanding of factors that can predict psychedelic experience is essential to both clinical progress and wider harm reduction frameworks. Ketamine, MDMA, LSD and psilocybin were selected for comparison due to their promising therapeutic effects and different mechanisms of action. The current study aimed to (a) identify factors that predict both positive and adverse psychedelic experience, and (b) compare these predictors across the four psychedelic substances. A thematic analysis was conducted on twenty-four subjective, first-person reports of psychedelic use (six per substance), sourced from the Erowid online database. The analysis revealed three external predictors (nature, music and preparation) and three internal predictors (understanding, mindset and motivation). Each predictor contained two sub-themes that further elucidated their meaning and impact. Nature and music emerged as potential tools for de-escalating adverse reactions to psychedelics, which was a novel finding. A comparison between substances further revealed that these predictors actually had different impacts, depending on the substance being taken. Finally, the importance of, and interrelationship between, preparation, mindset, understanding and motivation was made clear. The broader clinical and sociological implications of this were discussed, with particular reference to developing harm reduction frameworks. As psychedelic therapy and research continues to gain momentum, these findings constitute an early step in developing a more nuanced understanding of the factors shaping psychedelic experience.

Novel Trypanocidal Inhibitors that Block Glycosome Biogenesis by Targeting PEX3–PEX19 Interaction

Human pathogenic trypanosomatid parasites harbor a unique form of peroxisomes termed glycosomes that are essential for parasite viability. We and others previously identified and characterized the essential Trypanosoma brucei ortholog TbPEX3, which is the membrane-docking factor for the cytosolic receptor PEX19 bound to the glycosomal membrane proteins. Knockdown of TbPEX3 expression leads to mislocalization of glycosomal membrane and matrix proteins, and subsequent cell death. As an early step in glycosome biogenesis, the PEX3–PEX19 interaction is an attractive drug target. We established a high-throughput assay for TbPEX3–TbPEX19 interaction and screened a compound library for small-molecule inhibitors. Hits from the screen were further validated using an in vitro ELISA assay. We identified three compounds, which exhibit significant trypanocidal activity but show no apparent toxicity to human cells. Furthermore, we show that these compounds lead to mislocalization of glycosomal proteins, which is toxic to the trypanosomes. Moreover, NMR-based experiments indicate that the inhibitors bind to PEX3. The inhibitors interfering with glycosomal biogenesis by targeting the TbPEX3–TbPEX19 interaction serve as starting points for further optimization and anti-trypanosomal drug development.

Antarctic Fish as a Global Pollution Sensor: Metals Biomonitoring in a Twelve-Year Period

Antarctica represents a unique natural laboratory for ecotoxicological studies as it is characterized by low internal pollutants emissions but high external contamination levels. Indeed, warm temperatures promote pollutant evaporation (low latitudes), while cool temperatures (high latitudes) promote its deposition from the atmosphere on land/water. Metals are the most important pollutants in ecosystems and represent a serious and global threat to aquatic and terrestrial organisms. Since 2000, the risks posed by metals have led many States to ratify protocols aimed at reducing their emissions. Endemic Antarctic organisms represent excellent bioindicators in order to evaluate the efficacy of global measures adopted to mitigate pollutants release into the environment. In this study (supported by PNRA18-00133), we estimated the metals contamination levels and the metallothionein-1 expression in liver samples of two Antarctic fish species, the icefish Chionodraco hamatus and the red-blooded Trematomus bernacchii, collected in the same area during 2002 and 2014. The chosen area is located in the Ross Sea, a unique area as it is also isolated from the rest of the Southern Ocean. The analysis of contamination trends throughout this period showed, in both species, a significant increase over time of metals bioaccumulation and metallothionein-1 expression. In addition, our result clearly indicated that the detoxifying ability of the two organisms analyzed greatly differs, probably due to haemoglobin presence/absence. Our work represents an important early step to obtain valuable information in conservation strategies for both Antarctic and non-Antarctic ecosystems.

Molecular Manipulation of the miR396 and miR399 Expression Modules Alters the Response of Arabidopsis thaliana to Phosphate Stress

In plant cells, the molecular and metabolic processes of nucleic acid synthesis, phospholipid production, coenzyme activation and the generation of the vast amount of chemical energy required to drive these processes relies on an adequate supply of the essential macronutrient, phosphorous (P). The requirement of an appropriate level of P in plant cells is evidenced by the intricately linked molecular mechanisms of P sensing, signaling and transport. One such mechanism is the posttranscriptional regulation of the P response pathway by the highly conserved plant microRNA (miRNA), miR399. In addition to miR399, numerous other plant miRNAs are also required to respond to environmental stress, including miR396. Here, we exposed Arabidopsis thaliana (Arabidopsis) transformant lines which harbor molecular modifications to the miR396 and miR399 expression modules to phosphate (PO4) starvation. We show that molecular alteration of either miR396 or miR399 abundance afforded the Arabidopsis transformant lines different degrees of tolerance to PO4 starvation. Furthermore, RT-qPCR assessment of PO4-starved miR396 and miR399 transformants revealed that the tolerance displayed by these plant lines to this form of abiotic stress most likely stemmed from the altered expression of the target genes of these two miRNAs. Therefore, this study forms an early step towards the future development of molecularly modified plant lines which possess a degree of tolerance to growth in a PO4 deficient environment.

Tips on Halterbreaking Cattle

Many youth join 4-H with visions of exhibiting dairy or beef cattle. For those youth new to a dairy or beef project, halterbreaking their project animals is an early step to help prepare their project animal for exhibition. This new 2-page publication of the UF/IFAS 4-H Youth Development Program provides a brief list of tips for halterbreaking an animal. Written by Chris DeCubellis.https://edis.ifas.ufl.edu/4h421

Meta-analysis on reporting practices as a source of heterogeneity in in vitro cancer research

Background: Heterogeneity of results of exact same research experiments oppose a significant socio-economic burden. In vitro research presents the early step of basic science and drug development projects. Insufficient methodological reporting is likely to be one of the contributors to results heterogeneity, however, little knowledge on reporting habits of in vitro cancer research and their effects on results reproducibility is available. Glioblastoma is a form of brain cancer with largely unmet clinical need. Methods: Here we use systematic review to describe reporting practices in in vitro glioblastoma research using the U87-MG cell line and perform multilevel random-effects meta-analysis followed by meta-regression to explore sources of heterogeneity within that literature, and any associations between reporting characteristics and reported findings. Results: In 137 identified articles, the overall methodological reporting is disappointing, e.g., the control type, mediums glucose level and cell density are reported in only 36.5, 21.2 and 16.8 percent of the articles, respectively. After adjustments for different drug concentrations and treatment durations, a three-level meta-analysis proves meaningful results heterogeneity across the studies (I2 = 70.1%). Conclusions: Our results further support the ongoing efforts of establishing consensus reporting practices to elevate durability of results. By doing so, we hope that this work will raise awareness of how stricter reporting may help to improve the frequency of successful translation of preclinical results into human application, not only in neuro-oncology. Funding: We received no specific funding for this project.

Establishing a baseline of science communication skills in an undergraduate environmental science course

Background Seminal reports, based on recommendations by educators, scientists, and in collaboration with students, have called for undergraduate curricula to engage students in some of the same practices as scientists—one of which is communicating science with a general, non-scientific audience (SciComm). Unfortunately, very little research has focused on helping students develop these skills. An important early step in creating effective and efficient curricula is understanding what baseline skills students have prior to instruction. Here, we used the Essential Elements for Effective Science Communication (EEES) framework to survey the SciComm skills of students in an environmental science course in which they had little SciComm training. Results Our analyses revealed that, despite not being given the framework, students included several of the 13 elements, especially those which were explicitly asked for in the assignment instructions. Students commonly targeted broad audiences composed of interested adults, aimed to increase the knowledge and awareness of their audience, and planned and executed remote projects using print on social media. Additionally, students demonstrated flexibility in their skills by slightly differing their choices depending on the context of the assignment, such as creating more engaging content than they had planned for. Conclusions The students exhibited several key baseline skills, even though they had minimal training on the best practices of SciComm; however, more support is required to help students become better communicators, and more work in different contexts may be beneficial to acquire additional perspectives on SciComm skills among a variety of science students. The few elements that were not well highlighted in the students’ projects may not have been as intuitive to novice communicators. Thus, we provide recommendations for how educators can help their undergraduate science students develop valuable, prescribed SciComm skills. Some of these recommendations include helping students determine the right audience for their communication project, providing opportunities for students to try multiple media types, determining the type of language that is appropriate for the audience, and encouraging students to aim for a mix of communication objectives. With this guidance, educators can better prepare their students to become a more open and communicative generation of scientists and citizens.

VAL1 as an assembly platform co-ordinating co-transcriptional repression and chromatin regulation at Arabidopsis FLC

Polycomb (PcG) silencing is crucial for development across eukaryotes, but how PcG targets are regulated is still incompletely understood. The slow timescale of cold-induced PcG silencing at Arabidopsis thaliana FLOWERING LOCUS C (FLC) makes it an excellent system to dissect this mechanism. Binding of the DNA binding protein VAL1 to an FLC intronic RY motif within the PcG nucleation region is an early step in the silencing process. VAL1 interacts with APOPTOSIS AND SPLICING ASSOCIATED PROTEIN (ASAP) complex and POLYCOMB REPRESSIVE COMPLEX 1 (PRC1). Here, we show that ASAP and PRC1 function as co-repressors that quantitatively regulate FLC transcription. Upon the shift to cold PRC1-mediated H2Aub accumulates only at the nucleation region, is transiently maintained after transfer back to warm, but unlike the PRC2-delivered H3K27me3 does not spread across the locus. H2K27me3 thus provides long-term epigenetic silencing, whereas H2Aub is a transient repression signal. Overall, our work highlights how a DNA sequence-specific binding protein can act as an assembly platform co-ordinating the co-transcriptional repression and chromatin regulation necessary for Polycomb silencing.