National Institute on Drug Abuse - Intramural Research Program
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The opinions expressed are the NIDA IRP POTM Committee members’ own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government.
FARESHARE: An open-source apparatus for assessing drinking microstructure in socially housed rats. NPP—Digit Psychiatry Neurosci.
The authors describe an open-source and cost-effective system for monitoring drinking behavior in group housed rodents. The fully customizable system can measure both the volume consumed and drinking bouts microstructure in context of social behaviors.
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Adaptable, turn-on maturation (ATOM) fluorescent biosensors for multiplexed detection in cells Nature Methods
This paper by Sekhon et al, 2023 describes the creation of turn-on fluorescence sensors coupled to either monobody or nanobody. The fluorescent sensors can be paired with a monobody/nanobody to your protein of interest and optimized for fluorescence intensity.
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Investigation of daily patterns for smartphone keystroke dynamics based on loneliness and social isolation. Biomed Eng Lett
The current paper used a custom Android keyboard to study human behavioral patterns linked to loneliness over a five-week period and found distinctive patterns within the severe loneliness group. The study showcases a new digital biomarker to decode mental health conditions.
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Using a novel rapid alternating steering angles pulse sequence to evaluate the impact of theranostic ultrasound-mediated ultra-short pulse length on blood-brain barrier opening volume and closure, cavitation mapping, drug delivery feasibility, and safety Theranostics.
The current study from the Konofagou lab describes an advancement in FUS delivery parameters and instrumentation that allows the simultaneous opening and monitoring of BBB in two brain regions simultaneously. This preclinical study highlights new developments in FUS that expand its capabilities for safe, non-invasive gene and drug delivery to the brain for the potential treatment of neurological diseases. FUS may be a useful tool for evaluating therapeutics for substance use disorder.
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Complete biosynthesis of cannabinoids and their unnatural analogues in yeast. Nature
The study and medicinal use of cannabinoids has been hampered by the legal scheduling of Cannabis, the low in planta abundances of nearly all of the dozens of known cannabinoids, and their structural complexity, which limits bulk chemical synthesis. Here we report the complete biosynthesis of the major cannabinoids cannabigerolic acid, Δ9-tetrahydrocannabinolic acid, cannabidiolic acid, Δ9-tetrahydrocannabivarinic acid and cannabidivarinic acid in Saccharomyces cerevisiae, from the simple sugar galactose. Furthermore, we established a biosynthetic approach that harnessed the promiscuity of several pathway genes to produce cannabinoid analogues. Feeding different fatty acids to our engineered strains yielded cannabinoid analogues with modifications in the part of the molecule that is known to alter receptor binding affinity and potency [Read More]
The acceptability of overdose alert and response technologies: introducing the TPOM-ODART framework. Harm Reduct J
A TPOM-ODART framework, a model of overdose alert and response technologies (ODART) based on the existing health information technology TPOM dataset, was developed to better understand factors involved in harm reduction technology acceptability to people who use opioids (PWUO). Concerns of trust, readiness, accessibility, and capacity were found to be key factors in engaging and retaining PWUO in ODRAT interventions. [Read More]
Sensitive multicolor indicators for monitoring norepinephrine in vivo. Nat Methods.
Existing GPCR-based Norepinephrine sensors are based on alpha-2a adrenergic receptors and do not exhibit the kinetic properties needed to investigate in vivo NE dynamics in response to different drugs. Kagiampaki et al. developed a new set of fluorescent indicators based on the alpha-1a adrenergic receptors. The nLight sensors combined with fiber photometry and two-photon imaging could be used to investigate spatial and temporal aspects of Norepinephrine signaling in animal models of substance use disorder. [Read More]
Highly accurate protein structure prediction for the human proteome Nature.
Determining complete protein structures is difficult as sufficient quantities need to be purified; protein size, transmembrane domains, and susceptibility to conformational changes create inconsistencies; and the work can take months to years. Tunyasuvunakool et al. applied AlphaFold to predict full-length structures with detailed chemical components of nearly the entire human proteome (98.5%) as well as ~20 other organisms and provided this data in a public database. Since publication, the authors updated AlphaFold (version 2) shortening days-long prediction computation to minutes/hours and the database now has over 200 million protein structures. [Read More]
Engineering of NEMO as calcium indicators with large dynamics and high sensitivity. Nat Methods.
Current genetically encoded calcium indicators have suboptimal dynamic range and peak signal-to-baseline ratios. Li et al. engineered a new series of mNG-based calcium indicators (NEMO) that exhibit fast kinetics with up to 100-fold increase in dynamic range and 20-fold increase in signal-to-baseline ratios when NEMO sensors were compared to GCaMP6m or NCaMP7. Increased fluorescence and dynamic range of NEMO should facilitate the in vivo monitoring of calcium changes in deep brain structures and cellular organelles. [Read More]
Revealing the structure of pharmacobehavioral space through motion sequencing. Nat Neurosci.
Standard behavioral assays that are used for screening candidate therapeutic drugs, such as the elevated plus maze and forced swim test, yield only one or two dimensions of information. Wiltschko et al. used a machine learning algorithm called MoSeq (for motion sequencing) to analyze 3D video recordings of twenty minutes of open field mouse activity, thereby obtaining a much higher dimensional readout of behavior in response to a wide variety of psychoactive drugs and doses. [Read More]
