Effects of sex and remifentanil dose on rats' acquisition of responding for a remifentanil-conditioned reinforcer.

Opioid-conditioned reinforcement is thought to exacerbate opioid abuse and dependence. Sex/gender can influence opioid abuse behaviors, but the effects of sex/gender on opioid-conditioned reinforcement, specifically, are unclear. In this study, we compared new-response acquisition with opioid-conditioned reinforcement in male and female rats. First, separate groups received response-independent remifentanil injections (0.0-32.0 µg/kg, intravenous) and presentations of a light-noise stimulus. In the experimental groups, injections and stimulus presentations always co-occurred [paired Pavlovian conditioning (PAV)]; in the control groups, the two occurred independently of each other (random PAV). Next, in the instrumental acquisition (ACQ) sessions, two novel nose-poke manipulanda were introduced. All animals (regardless of sex, dose, and PAV type) could respond in the active nose-poke, which produced the stimulus alone, or in the inactive nose-poke. Both males and females dose-dependently acquired nose-poke responding (active>inactive) after paired PAV, but not after random PAV. Therefore, the stimulus was a conditioned reinforcer. We identified three sex differences. First, only females acquired responding after paired PAV with 32.0 µg/kg remifentanil. Second, using a progressive ratio schedule for ACQ, both sexes acquired responding, but females made significantly more active responses. Third, when a single session of PAV was conducted, only males acquired responding. Thus, rats' sex interacts with pharmacological and environmental factors to determine opioid-conditioned reinforcement.

Assessing state stem cell programs in the United States: how has state funding affected publication trends?

Several states responded to federal funding limitations placed on human embryonic stem cell research and the potential of the field by creating state stem cell funding programs, yet little is known about the impact of these programs. Here we examine how state programs have affected publication trends in four states.

Plasma membrane recovery kinetics of a microfluidic intracellular delivery platform.

Intracellular delivery of materials is a challenge in research and therapeutic applications. Physical methods of plasma membrane disruption have recently emerged as an approach to facilitate the delivery of a variety of macromolecules to a range of cell types. We use the microfluidic CellSqueeze delivery platform to examine the kinetics of plasma membrane recovery after disruption and its dependence on the calcium content of the surrounding buffer (recovery time ∼ 5 min without calcium vs. ∼ 30 s with calcium). Moreover, we illustrate that manipulation of the membrane repair kinetics can yield up to 5× improvement in delivery efficiency without significantly impacting cell viability. Membrane repair characteristics initially observed in HeLa cells are shown to translate to primary naïve murine T cells. Subsequent manipulation of membrane repair kinetics also enables the delivery of larger materials, such as antibodies, to these difficult to manipulate cells. This work provides insight into the membrane repair process in response to mechanical delivery and could potentially enable the development of improved delivery methods.

Advances in microfluidic cell separation and manipulation.

Cellular separations are required in many contexts in biochemical and biomedical applications for the identification, isolation, and analysis of phenotypes or samples of interest. Microfluidics is uniquely suited for handling biological samples, and emerging technologies have become increasingly accessible tools for researchers and clinicians. Here, we review advances in the last few years in techniques for microfluidic cell separation and manipulation. Applications such as high-throughput cell and organism phenotypic screening, purification of heterogeneous stem cell populations, separation of blood components, and isolation of rare cells in patients highlight some of the areas in which these technologies show great potential. Continued advances in separation mechanisms and understanding of cellular systems will yield further improvements in the throughput, resolution, and robustness of techniques.