Two-year review of firearm-related DNA casework evidence: A triage process to improve quality and efficiency.

A two-year casework review of 617 firearm-related submissions representing 119 cases has provided a DNA testing triage template for prioritizing and processing touch evidence associated with firearms and firearm accessories. The evidence consisted of swabbings from various locations of a firearm or a firearm-related item, and each submission was assigned to one of the following descriptive groups: Body, Magazine, Trigger Area, Rifles, Gun Accessories, Barrel, Miscellaneous, or Revolvers. Ultimately, there were 543 submissions analyzed from DNA extraction through electrophoresis, and interpretable profiles evaluated to determine eligibility for entry into The Combined DNA Index System (CODIS). All samples were subjected to the same validated DNA technologies and methodologies used in the laboratory during the study's February 2020 through February 2022 time period, allowing for direct comparison of data. A DNA profile, defined as the detection of at least one allele above the analytical threshold, was detected in 478 samples (88%). Interpretable profiles, defined as a DNA profile that, as a whole or in part, is deemed to be of sufficient quality that it is suitable for comparison to known DNA standards for the purpose of inclusion or exclusion, were observed in 287 samples (53%). In this sample set, there were 12 DNA profiles generated from nine different cases that were uploaded into CODIS, resulting in three CODIS hits. Additionally, there were 163 standards associated with these cases that were entered into CODIS. As a result of this extensive review, the data strongly supported modifications to both the Forensic Biology Unit's firearm-related Case Submission Policy and the laboratory's DNA process for triaging samples from firearms.

A Selective Adenylyl Cyclase 1 Inhibitor Relieves Pain Without Causing Tolerance.

Among the ten different adenylyl cyclase isoforms, studies with knockout animals indicate that inhibition of AC1 can relieve pain and reduce behaviors linked to opioid dependence. We previously identified ST034307 as a selective inhibitor of AC1. The development of an AC1-selective inhibitor now provides the opportunity to further study the therapeutic potential of inhibiting this protein in pre-clinical animal models of pain and related adverse reactions. In the present study we have shown that ST034307 relives pain in mouse models of formalin-induced inflammatory pain, acid-induced visceral pain, and acid-depressed nesting. In addition, ST034307 did not cause analgesic tolerance after chronic dosing. We were unable to detect ST034307 in mouse brain following subcutaneous injections but showed a significant reduction in cAMP concentration in dorsal root ganglia of the animals. Considering the unprecedented selectivity of ST034307, we also report the predicted molecular interaction between ST034307 and AC1. Our results indicate that AC1 inhibitors represent a promising new class of analgesic agents that treat pain and do not result in tolerance or cause disruption of normal behavior in mice. In addition, we outline a unique binding site for ST034307 at the interface of the enzyme's catalytic domain.

Adenylyl cyclase 7 and neuropsychiatric disorders: A new target for depression?

Adenylyl cyclases (ACs) are enzymes that catalyze the production of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP). Humans express nine isoforms of membranous ACs and a soluble AC. Studies with genetic knockout or overexpression rodent models have indicated that AC isoforms may be targeted to achieve specific therapeutic outcomes. AC1, for instance, has been suggested and pursued as a target for relieving pain. Notably, previous studies examining genetically modified mice as well as human genetic polymorphisms have suggested a link between AC7 activity and depressive disorders. In the present review we present an overview on AC function and discuss the most recent developments to target AC isoforms for drug therapies. We next focus on discussing the available literature on the molecular and animal pharmacology of AC7 highlighting the available studies on the role of AC7 in depressive disorders. In addition, we discuss other possible physiological functions of AC7 relating to ethanol effects and the immune system and conclude with considerations about pharmacological modulation of AC7.