Gonadal steroids modulate CNS plasticity, including phrenic long-term facilitation (pLTF), a form of spinal respiratory neuroplasticity resulting in increased phrenic nerve motor output following exposure to acute intermittent hypoxia (aIH; three 5 min episodes, 10.5% O 2 ). Despite the importance of respiratory system neuroplasticity, and its dependence on estrogen in males, little is known about pLTF expression or mechanisms of estrogen signaling in females. Here, we tested the hypotheses that (1) pLTF expression in young, gonadally intact female rats would be expressed during estrous cycle stages in which 17␤-estradiol (E2) is naturally high (e.g., proestrus vs estrus), (2) pLTF would be absent in ovariectomized (OVX) rats and in physiological conditions in which serum progesterone, but not E2, is elevated (e.g., lactating rats, 3-10 d postpartum), and (3) acute E2 administration would be sufficient to restore pLTF in OVX rats. Recordings of phrenic nerve activity in female Sprague Dawley rats (3-4 months) revealed a direct correlation between serum E2 levels and pLTF expression in cycling female rats. pLTF was abolished with OVX, but was re-established by acute E2 replacement (3 h, intraperitoneal). To identify underlying E2 signaling mechanisms, we intrathecally applied BSA-conjugated E2 over the spinal phrenic motor nucleus and found that pLTF expression was restored within 15 min, suggesting nongenomic E2 effects at membrane estrogen receptors. These data are the first to investigate the role of ovarian E2 in young cycling females, and to identify a role for nongenomic estrogen signaling in any form of respiratory system neuroplasticity.

When informed of the diagnosis and treatment options in an unhurried, supportive setting, and when encouraged to seek further consultations as desired, breast cancer patients make appropriate therapeutic choices about mastectomy or breast conservation therapy.

Although inflammation is prevalent in many clinical disorders challenging breathing, we are only beginning to understand the impact of inflammation on neural mechanisms of respiratory control. We recently demonstrated one form of respiratory motor plasticity is extremely sensitive to even mild inflammation induced by a single night (8 h) of intermittent hypoxia (IH-1), mimicking aspects of obstructive sleep apnea. Specifically, phrenic long-term facilitation (pLTF) following moderate acute intermittent hypoxia (AIH) is abolished by IH-1, but restored by high doses of the non-steroidal anti-inflammatory drug, ketoprofen. Since a major target of ketoprofen is cyclooxygenase (COX) enzymes, we tested the involvement of COX in IH-1 suppression of pLTF using the selective COX inhibitor NS-398. Systemic COX inhibition (3 mg/kg, i.p., 3 h before AIH) had no effect on pLTF in normoxia treated rats (76 ± 40% change from baseline, n = 6), and did not restore pLTF in IH-1 treated rats (-9 ± 7% baseline, n = 6). Similarly, spinal COX inhibition (27 mM, 12 μl, i.t.) had no effect on pLTF in normoxic rats (76 ± 34% baseline, n = 7), and did not significantly restore pLTF after IH-1 (37 ± 18% baseline, n = 7). COX-2 protein is expressed in identified phrenic motor neurons of both normoxia and IH-1 exposed rats, but immunolabeling was minimal in surrounding microglia; IH-1 had no discernable effect on COX-2 immunoreactivity. We conclude that the inflammatory impairment of pLTF by IH-1 is independent of COX enzyme activity or upregulated COX-2 expression.

Crop variety mixtures can provide many benefits, including pathogen suppression and increased yield and yield stability. However, these benefits do not necessarily occur in all mixtures, and the benefits of diversity may be compromised by disadvantages due to increased crop heterogeneity. In-field development of mixtures by assembling many combinations of crop genotypes without prior expectation about which genotypes need to be combined to produce well-performing mixtures results in prohibitively large designs. Therefore, effective tools are required to narrow down the number of promising variety mixtures, and to then identify in experiments which of these deliver the highest benefits. Here, we first review current knowledge about the mechanisms underlying effects in ecological diversity experiments and in current agricultural applications. We then discuss some of the principal difficulties arising in the application of this knowledge to develop good variety mixtures. We also discuss non-conventional approaches to solve some of these issues. In particular, we highlight the potential and limitations of trait-based methods to determine good variety mixing partners, and argue that non-traditional traits and trait-derived metrics may be needed for the trait-based approach to deliver its full potential. Specifically, we argue that good mixing partners can be identified using modern genetic and genomic approaches. Alternatively, good mixtures may be obtained by combining varieties that respond differently to environmental variation; such varieties could easily be identified in standard variety testing trials. Preliminary analyses show that niche differences underlying the different environmental responses can indicate functional complementarity and promote mixture yield and yield stability.