Review and Call for Improved Cannabis Measurement and the Potential for Leveraging Cannabis Seed-To-Sale Systems.

International consensus has emerged, which proposes that the measurement and standardization of the quantity of THC potency, or dose (mgTHC), is a requisite for identifying consistent relationships between patterns of cannabis use and the risk for negative health outcomes, especially critical given the increasing number of U.S. states and European countries considering legalizing cannabis for recreational use.

Delay discounting is associated with addiction and mental health measures while controlling for health behaviors and health barriers in a large US sample.

Background: Excessive discounting of future rewards [delay discounting (DD)] may be a transdiagnostic process and treatment target underlying behavioral health outcomes, including trauma, depression, anxiety, and problematic substance use. However, multiple health behaviors and barriers are also related to these outcomes, including social media usage, adverse childhood experiences (ACEs), sleep quality, healthcare access, housing status, and exercise. To extend research examining DD as transdiagnostic process, we recruited a large, heterogenous sample to examine the association between DD, problematic substance use, and mental health outcomes while controlling for certain health behaviors and health barriers.

Role of PIP39 in oxidative stress response appears conserved in kinetoplastids.

Kinetoplastids, a group of flagellated protists that are often insect intestinal parasites, encounter various sources of oxidative stress. Such stressors include reactive oxygen species, both internally produced within the protist, and induced externally by host immune responses. This investigation focuses on the role of a highly conserved aspartate-based protein phosphatase, PTP-Interacting protein (PIP39) in managing oxidative stress.

Blastocrithidia nonstop mitochondrial genome and its expression are remarkably insulated from nuclear codon reassignment.

The canonical stop codons of the nuclear genome of the trypanosomatid Blastocrithidia nonstop are recoded. Here, we investigated the effect of this recoding on the mitochondrial genome and gene expression. Trypanosomatids possess a single mitochondrion and protein-coding transcripts of this genome require RNA editing in order to generate open reading frames of many transcripts encoded as 'cryptogenes'.

Kinetoplast Genome of spp. Is under Strong Purifying Selection.

Instability is an intriguing characteristic of many protist genomes, and trypanosomatids are not an exception in this respect. Some regions of trypanosomatid genomes evolve fast. For instance, the trypanosomatid mitochondrial (kinetoplast) genome consists of fairly conserved maxicircle and minicircle molecules that can, nevertheless, possess high nucleotide substitution rates between closely related strains.

Circular mitochondrial-encoded mRNAs are a distinct subpopulation of mitochondrial mRNA in Trypanosoma brucei.

Since the first identification of circular RNA (circRNA) in viral-like systems, reports of circRNAs and their functions in various organisms, cell types, and organelles have greatly expanded. Here, we report the first evidence, to our knowledge, of circular mRNA in the mitochondrion of the eukaryotic parasite, Trypanosoma brucei. While using a circular RT-PCR technique developed to sequence mRNA tails of mitochondrial transcripts, we found that some mRNAs are circularized without an in vitro circularization step normally required to produce PCR products.

Circular mitochondrial-encoded mRNAs are a distinct subpopulation of mitochondrial mRNA in .

Since the first identification of circular RNA (circRNA) in viral-like systems, reports of circRNAs and their functions in various organisms, cell types, and organelles have greatly expanded. Here, we report the first evidence of circular mRNA in the mitochondrion of the eukaryotic parasite, . While using a circular RT-PCR technique developed to sequence mRNA tails of mitochondrial transcripts, we found that some mRNAs are circularized without an circularization step normally required to produce PCR products.

Mitochondrial RNA editing in : New tools, new revelations.

The kinetoplastids are unicellular flagellates that derive their name from the 'kinetoplast', a region within their single mitochondrion harboring its organellar genome of high DNA content, called kinetoplast (k) DNA. Some protein products of this mitochondrial genome are encoded as cryptogenes; their transcripts require editing to generate an open reading frame. This happens through RNA editing, whereby small regulatory guide (g)RNAs direct the proper insertion and deletion of one or more uridines at each editing site within specific transcript regions.

strain and starvation-driven mitochondrial RNA editing and transcriptome variability.

is a unicellular protistan parasitic species that is comprised of strains and isolates exhibiting high levels of genetic and metabolic variability. In the insect vector, it is known to be highly responsive to starvation, a signal for progression to a life stage in which it can infect mammalian cells. Most mRNAs encoded in its mitochondrion require the targeted insertion and deletion of uridines to become translatable transcripts.

Using a Community-Based Participatory Approach to Address Gender Equity in Academic Medicine: The Center for Women in Medicine and Science at the University of Minnesota.

Many medical schools are instituting gender equity initiatives to address long-standing inequities (e.g., salary, leadership positions, resource distribution) between women and men in academic medicine.

Reintegrating Biology Through the Nexus of Energy, Information, and Matter.

Information, energy, and matter are fundamental properties of all levels of biological organization, and life emerges from the continuous flux of matter, energy, and information. This perspective piece defines and explains each of the three pillars of this nexus. We propose that a quantitative characterization of the complex interconversions between matter, energy, and information that comprise this nexus will help us derive biological insights that connect phenomena across different levels of biological organization.

Complete minicircle genome of Leptomonas pyrrhocoris reveals sources of its non-canonical mitochondrial RNA editing events.

Uridine insertion/deletion (U-indel) editing of mitochondrial mRNA, unique to the protistan class Kinetoplastea, generates canonical as well as potentially non-productive editing events. While the molecular machinery and the role of the guide (g) RNAs that provide required information for U-indel editing are well understood, little is known about the forces underlying its apparently error-prone nature. Analysis of a gRNA:mRNA pair allows the dissection of editing events in a given position of a given mitochondrial transcript.

The Remarkable Metabolism of : Genomic Predictions.

A recently redescribed two-flagellar trypanosomatid is insensitive to the classical inhibitors of respiration and thrives under anaerobic conditions. Using genomic and transcriptomic data, we analyzed its genes of the core metabolism and documented that subunits of the mitochondrial respiratory complexes III and IV are ablated, while those of complexes I, II, and V are all present, along with an alternative oxidase. This explains the previously reported conversion of glucose to acetate and succinate by aerobic fermentation.

Probabilistic models of biological enzymatic polymerization.

In this study, hierarchies of probabilistic models are evaluated for their ability to characterize the untemplated addition of adenine and uracil to the 3' ends of mitochondrial mRNAs of the human pathogen Trypanosoma brucei, and for their generative abilities to reproduce populations of these untemplated adenine/uridine "tails". We determined the most ideal Hidden Markov Models (HMMs) for this biological system. While our HMMs were not able to generatively reproduce the length distribution of the tails, they fared better in reproducing nucleotide composition aspects of the tail populations.

A Global Analysis of Enzyme Compartmentalization to Glycosomes.

In kinetoplastids, the first seven steps of glycolysis are compartmentalized into a glycosome along with parts of other metabolic pathways. This organelle shares a common ancestor with the better-understood eukaryotic peroxisome. Much of our understanding of the emergence, evolution, and maintenance of glycosomes is limited to explorations of the dixenous parasites, including the enzymatic contents of the organelle.

A link between mitochondrial gene expression and life stage morphologies in Trypanosoma cruzi.

The protozoan Trypanosoma cruzi has a complicated dual-host life cycle, and starvation can trigger transition from the replicating insect stage to the mammalian-infectious nonreplicating insect stage (epimastigote to trypomastigote differentiation). Abundance of some mature RNAs derived from its mitochondrial genome increase during culture starvation of T. cruzi for unknown reasons.

Revisiting Trypanosome Mitochondrial Genome Mysteries: Broader and Deeper.

What do the products of a genome do, and when and why are they needed? For the protein products of the trypanosomatid parasites' mitochondrial genomes, the total expressed protein repertoire and the identities of the more difficult-to-characterize products have been challenging to acquire. Comparative genomics and new technologies may resolve that.

High throughput sequencing revolution reveals conserved fundamentals of U-indel editing.

Among Euglenozoans, mitochondrial RNA editing occurs in the diplonemids and in the kinetoplastids that include parasitic trypanosomes. Yet U-indel editing, in which open reading frames (ORFs) on mRNAs are generated by insertion and deletion of uridylates in locations dictated by guide RNAs, appears confined to kinetoplastids. The nature of guide RNA and edited mRNA populations has been cursorily explored in a surprisingly extensive number of species over the years, although complete sets of fully edited mRNAs for most kinetoplast genomes are largely missing.

Gene expression to mitochondrial metabolism: Variability among cultured Trypanosoma cruzi strains.

The insect-transmitted protozoan parasite Trypanosoma cruzi experiences changes in nutrient availability and rate of flux through different metabolic pathways across its life cycle. The species encompasses much genetic diversity of both the nuclear and mitochondrial genomes among isolated strains. The genetic or expression variation of both genomes are likely to impact metabolic responses to environmental stimuli, and even steady state metabolic function, among strains.

Trypanosomatid mitochondrial RNA editing: dramatically complex transcript repertoires revealed with a dedicated mapping tool.

RNA editing by targeted insertion and deletion of uridine is crucial to generate translatable mRNAs from the cryptogenes of the mitochondrial genome of kinetoplastids. This type of editing consists of a stepwise cascade of reactions generally proceeding from 3' to 5' on a transcript, resulting in a population of partially edited as well as pre-edited and completely edited molecules for each mitochondrial cryptogene of these protozoans. Often, the number of uridines inserted and deleted exceed the number of nucleotides that are genome-encoded.

Tail characteristics of Trypanosoma brucei mitochondrial transcripts are developmentally altered in a transcript-specific manner.

The intricate life cycle of Trypanosoma brucei requires extensive regulation of gene expression levels of the mtRNAs for adaptation. Post-transcriptional gene regulatory programs, including unencoded mtRNA 3' tail additions, potentially play major roles in this adaptation process. Intriguingly, T.

A putative ATP/GTP binding protein affects Leishmania mexicana growth in insect vectors and vertebrate hosts.

Background: Leishmania virulence factors responsible for the complicated epidemiology of the various leishmaniases remain mainly unidentified. This study is a characterization of a gene previously identified as upregulated in two of three overlapping datasets containing putative factors important for Leishmania's ability to establish mammalian intracellular infection and to colonize the gut of an insect vector.

Methodology/principal Findings: The investigated gene encodes ATP/GTP binding motif-containing protein related to Leishmania development 1 (ALD1), a cytosolic protein that contains a cryptic ATP/GTP binding P-loop.