Small molecule APOL1 inhibitors as a precision medicine approach for APOL1-mediated kidney disease.

Chronic kidney disease affects ~10% of people worldwide and there are no disease modifying therapeutics that address the underlying cause of any form of kidney disease. Genome wide association studies have identified the G1 and G2 variants in the apolipoprotein L1 (APOL1) gene as major contributors to a subtype of proteinuric kidney disease now referred to as APOL1-mediated kidney disease (AMKD). We hypothesized that inhibition of APOL1 could have therapeutic potential for this genetically-defined form of kidney disease.

Aeromedical evacuation-relevant hypobaria following traumatic brain injury in rats contributes to cerebral blood flow depression, altered neurochemistry, and increased neuroinflammation.

Aircraft cabins are routinely pressurized to the equivalent of 8000 ft altitude. Exposure of lab animals to aeromedical evacuation relevant hypobaria after traumatic brain injury worsens neurological outcomes, which is paradoxically exacerbated by hyperoxia. This study tested the hypothesis that exposure of rats to hypobaria following cortical impact reduces cerebral blood flow, increases neuroinflammation, and alters brain neurochemistry.

Behavioral assessment of well-being in the naïve laboratory ferret (Mustela putorius furo).

Domestic ferrets (Mustela putorius furo) are an emerging model species in biomedical research. While behavioral studies are a critical translational tool for evaluating neurologic function in disease models and toxicology studies, there is a lack of ferret-specific behavioral assays and corresponding data on baseline behavior. Play behavior is a promising target for evaluation of psychological well-being, particularly because ferrets engage in solitary and social play well into adulthood.

Clinical study design strategies to mitigate confounding effects of time-dependent clearance on dose optimization of therapeutic antibodies.

Time-dependent pharmacokinetics (TDPK) is a frequent confounding factor that misleads exposure-response (ER) analysis of therapeutic antibodies, where a decline in clearance results in increased drug exposure over time in patients who respond to therapy, causing a false-positive ER finding. The object of our simulation study was to explore the influence of clinical trial designs on the frequency of false-positive ER findings. Two previously published population PK models representative of slow- (pembrolizumab) and fast-onset (rituximab) TDPK were used to simulate virtual patient cohorts with time-dependent clearance and the frequency of false-positive ER findings.

Warm temperature inhibits cytoplasmic incompatibility induced by endosymbiotic Rickettsiella in spider hosts.

Bacterial endosymbionts manipulate reproduction in arthropods to increase their prevalence in the host population. One such manipulation is cytoplasmic incompatibility (CI), wherein the bacteria sabotage sperm in infected males to reduce the hatch rate when mated with uninfected females, but zygotes are 'rescued' when that male mates with an infected female. In the spider Mermessus fradeorum (Linyphiidae), Rickettsiella symbionts cause variable levels of CI.