Effects of Cannabichromene on Pain and Neuroinflammation in HIV-1 TAT Transgenic Mice

HIV-1 TransActivator of Transcription (Tat) is a vital regulatory protein involved in HIV replication and implicated in development of HIV-associated pain and neurocognitive deficits. Tat is thought to contribute to these pathologies through proinflammatory pathways. Developing mechanisms to curb Tat-mediated inflammation is a key step in improving the quality of life of those living with HIV. Both recreational and medicinal cannabis use is prevalent among many people living with HIV; given this prevalence and the perceived anti-inflammatory benefits of cannabis use, it is important to investigate how chemical constituents of cannabis may impact HIV. In the present study, the effects of Cannabichromene (CBC) were studied in relation to Tat-mediated pain and inflammation in female mice. In the acetic acid writhing test for visceral pain, CBC reduced pain behaviors, and Tat expression increased pain response. However, in the formalin test, CBC showed no significant effect on pain behaviors, and Tat-expression reduced total pain behaviors. In situ analysis of microglial Periaqueductal Gray (PAG) tissue samples revealed that CBC decreased microglial activation, a marker of inflammation, and Tat expression increased microglial activation. Taken together, these results encourage further investigation into the potential interactions of CBC and Tat to elucidate the impact of CBC administration on Tat-mediated pain and inflammation

Roles of Extracellular Vesicles in Opioid Addiction: Potential Applications

Extracellular Vesicles (EVs) are lipid-bilayer membranous vesicles that facilitate intercellular communication via their secretion. EVs contain a variety of cargoes that reflect the intracellular environment of their host cells, and these cargoes can induce functional changes in recipient cells. A wide body of previous research has demonstrated that EVs play a role in a diverse range of disease pathologies as well as regular function and have emerged as promising vehicles for therapeutics and drug-delivery systems. Unsurprisingly, some work has recently been published implicating EVs in drug addiction pathways and therapeutics. Given the pressing scope of the opioid misuse and abuse in the U.S., it is necessary to consider the role of EVs in the development of opioid dependence and tolerance, as well as their role in potential therapeutics. The current review seeks to identify work investigating the role of EVs in opioid addiction and identify gaps and future directions in the literature.https://digitalcommons.unmc.edu/surp2020/1024/thumbnail.jp

Role of Extracellular Vesicles in Substance Abuse and HIV-Related Neurological Pathologies

Extracellular vesicles (EVs) are a broad, heterogeneous class of membranous lipid-bilayer vesicles that facilitate intercellular communication throughout the body. As important carriers of various types of cargo, including proteins, lipids, DNA fragments, and a variety of small noncoding RNAs, including miRNAs, mRNAs, and siRNAs, EVs may play an important role in the development of addiction and other neurological pathologies, particularly those related to HIV. In this review, we summarize the findings of EV studies in the context of methamphetamine (METH), cocaine, nicotine, opioid, and alcohol use disorders, highlighting important EV cargoes that may contribute to addiction. Additionally, as HIV and substance abuse are often comorbid, we discuss the potential role of EVs in the intersection of substance abuse and HIV. Taken together, the studies presented in this comprehensive review shed light on the potential role of EVs in the exacerbation of substance use and HIV. As a subject of growing interest, EVs may continue to provide information about mechanisms and pathogenesis in substance use disorders and CNS pathologies, perhaps allowing for exploration into potential therapeutic options

The Structure of Episodic Memory: Ganeri's ‘Mental Time Travel and Attention’

We offer a framework for assessing what the structure of episodic memory might be, if one accepts the Buddhist denial of persisting selves. This paper is a response to Jonardon Ganeri's paper "Mental time travel and attention", which explores Buddhaghosa's ideas about memory. (It will eventually be published with a reply by Ganeri)

Transcriptional regulatory networks underlying gene expression changes in Huntington's disease

Abstract Transcriptional changes occur presymptomatically and throughout Huntington's disease (HD), motivating the study of transcriptional regulatory networks (TRNs) in HD. We reconstructed a genome‐scale model for the target genes of 718 transcription factors (TFs) in the mouse striatum by integrating a model of genomic binding sites with transcriptome profiling of striatal tissue from HD mouse models. We identified 48 differentially expressed TF‐target gene modules associated with age‐ and CAG repeat length‐dependent gene expression changes in Htt CAG knock‐in mouse striatum and replicated many of these associations in independent transcriptomic and proteomic datasets. Thirteen of 48 of these predicted TF‐target gene modules were also differentially expressed in striatal tissue from human disease. We experimentally validated a specific model prediction that SMAD3 regulates HD‐related gene expression changes using chromatin immunoprecipitation and deep sequencing (ChIP‐seq) of mouse striatum. We found CAG repeat length‐dependent changes in the genomic occupancy of SMAD3 and confirmed our model's prediction that many SMAD3 target genes are downregulated early in HD

Heart failure in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies conference

The incidence and prevalence of heart failure (HF) and chronic kidney disease (CKD) are increasing, and as such a better understanding of the interface between both conditions is imperative for developing optimal strategies for their detection, prevention, diagnosis, and management. To this end, Kidney Disease: Improving Global Outcomes (KDIGO) convened an international, multidisciplinary Controversies Conference titled Heart Failure in CKD. Breakout group discussions included (i) HF with preserved ejection fraction (HFpEF) and nondialysis CKD, (ii) HF with reduced ejection fraction (HFrEF) and nondialysis CKD, (iii) HFpEF and dialysis-dependent CKD, (iv) HFrEF and dialysis-dependent CKD, and (v) HF in kidney transplant patients. The questions that formed the basis of discussions are available on the KDIGO website http://kdigo.org/conferences/heart-failure-in-ckd/, and the deliberations from the conference are summarized here

The visual perception of emotion from masks.

Fifty-one adults evaluated visually-perceived emotions from 32 masks. These masks (held in the collection of the Kentucky Museum, located on the campus of Western Kentucky University) were created by artists from a wide variety of cultures spanning multiple continents. Each participant evaluated every mask along six dimensions: happiness, sadness, anger, fear, surprise, and disgust. No previous scientific study has ever studied the general effectiveness of masks (other than Japanese Noh masks) in producing perceptions of human emotion. The results showed that the masks were effective in producing substantial variations in perceived happiness, sadness, anger, fear, surprise, and disgust. The ability of the masks to produce effective perceptions of emotion was due to the artists' inclusion of facial features that reliably signal emotions in everyday life