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Carr, A. L.

Publications and source records attributed to Carr, A. L..

4 recordsLinked to original sources

Striatal dopamine availability peaks in adulthood and undergoes age-dependent modulation

Age is a risk factor for several psychiatric disorders. An adolescent peak in striatal dopamine availability is thought to contribute to the neuropsychiatric vulnerability. However, the lifespan trajectory of striatal dopamine release capacity is undefined in most species. Here, we measured lifespan trajectories of striatal dopamine in primates and rodents and identified a delayed developmental peak in adulthood and age-dependent changes in dopamine release regulation by GABA and acetylcholine across species.

neuroscience↗

Human research islet cell culture outcomes at the Alberta Diabetes Institute IsletCore

Human islets from deceased organ donors have made important contributions to our understanding of pancreatic endocrine function and continue to be an important resource for research studies aimed at understanding, treating, and preventing diabetes. Understanding the impacts of isolation and culture upon the yield of human islets for research is important for planning research studies and islet distribution to distant laboratories. Here we examine islet isolation and cell culture outcomes at the Alberta Diabetes Institute (ADI) IsletCore (n=197). Research-focused isolations typically have a lower yield of islet equivalents (IEQ), with a median of 252,876 IEQ, but a higher purity (median 85%) than clinically-focused isolations before culture. The median recovery of IEQs after culture was 75%, suggesting some loss. This was associated with a shift towards smaller islet particles, indicating possible islet fragmentation, and occurred within 24 hours with no further loss after longer periods of culture (up to 136 hours). No overall change in stimulation index as a measure of islet function was seen with culture time. These findings were replicated in a representative cohort of clinical islet preparations from the Clinical Islet Transplant Program at the University of Alberta. Thus, loss of islets occurs within 24 hours of isolation and there is no further impact of extended culture prior to islet distribution for research.

cell biology↗

Transcriptome Profiles of Anopheles gambiae Harboring Natural Low-Level Plasmodium Infection Reveal Adaptive Advantages for the Mosquito

Anopheline mosquitoes are the sole vectors for the Plasmodium pathogens responsible for malaria, which is among the oldest and most devastating of human diseases. The continuing global impact of malaria reflects the evolutionary success of a complex vector-pathogen relationship that accordingly has been the long-term focus of both debate and study. An open question in the biology of malaria transmission is the impact of naturally occurring low-level Plasmodium infections of the vector on the mosquitos health and longevity as well as critical behaviors such as host- preference/seeking. To begin to answer this, we have completed a comparative RNAseq-based transcriptome profile study examining the effect of biologically salient, salivary gland transmission- stage Plasmodium infection on the molecular physiology of Anopheles gambiae s.s. head, sensory appendage, and salivary glands. When compared with their uninfected counterparts, Plasmodium infected mosquitoes exhibit increased transcript abundance of genes associated with olfactory acuity as well as a range of synergistic processes that align with increased fitness based on both anti-aging and reproductive advantages. Taken together, these data argue against the long-held paradigm that malaria infection is pathogenic for anophelines and, instead, suggests there are biological and evolutionary advantages for the mosquito that drive the preservation of its high vectorial capacity.

molecular biology↗

Ticks Home in on Body Heat: A New Understanding of Ectoparasite Host-Seeking and Repellent Action

Ticks are second only to mosquitoes as vectors of disease to humans and animals. Commercial insect repellents reduce or prevent potentially infectious tick bites by disrupting tick host-seeking behavior. Tick host-seeking is mainly ascribed to the Hallers organ, a complex sensory structure on the tick foreleg that detects odors, carbon dioxide and heat 4-7, but these host-seeking mechanisms and the mechanism of their disruption by repellents are not well understood1,2. There is anecdotal evidence that ticks and other ectoparasites are attracted to heat, but it has never been demonstrated that they use radiant heat to detect hosts at a distance. In fact, previous attempts to do this have concluded that radiant heat is not used by ticks. Here we show that Amblyomma americanum and Dermacentor variabilis ticks can sense and home in on a human from several meters away, guided by radiant heat sensed by the Hallers organ, and specifically the capsule, a covered spherical pit organ. An aperture in the capsule cover confers directionality and highly reflective interior surfaces of the capsule provide high sensitivity. Low concentrations of the insect repellents DEET, picaridin, 2-undecanone, citronellal and nootkatone eliminate thermotaxis without affecting olfactory-stimulated host-seeking behavior. Our results demonstrate that the tick Hallers organ capsule is a radiant heat sensor used in host-finding and that repellents disrupt this sense at concentrations that do not disrupt olfaction. We anticipate this discovery to significantly aid insect repellent research and development of innovative strategies for protection against ectoparasites and vector-borne disease.

neuroscience↗