Entorhinal Denervation Induces Homeostatic Synaptic Scaling of Excitatory Postsynapses of Dentate Granule Cells in Mouse Organotypic Slice Cultures

Denervation-induced changes in excitatory synaptic strength were studied following entorhinal deafferentation of hippocampal granule cells in mature (≥3 weeks old) mouse organotypic entorhino-hippocampal slice cultures. Whole-cell patch-clamp recordings revealed an increase in excitatory synaptic strength in response to denervation during the first week after denervation. By the end of the second week synaptic strength had returned to baseline. Because these adaptations occurred in response to the loss of excitatory afferents, they appeared to be in line with a homeostatic adjustment of excitatory synaptic strength. To test whether denervation-induced changes in synaptic strength exploit similar mechanisms as homeostatic synaptic scaling following pharmacological activity blockade, we treated denervated cultures at 2 days post lesion for 2 days with tetrodotoxin. In these cultures, the effects of denervation and activity blockade were not additive, suggesting that similar mechanisms are involved. Finally, we investigated whether entorhinal denervation, which removes afferents from the distal dendrites of granule cells while leaving the associational afferents to the proximal dendrites of granule cells intact, results in a global or a local up-scaling of granule cell synapses. By using computational modeling and local electrical stimulations in Strontium (Sr2+)-containing bath solution, we found evidence for a lamina-specific increase in excitatory synaptic strength in the denervated outer molecular layer at 3–4 days post lesion. Taken together, our data show that entorhinal denervation results in homeostatic functional changes of excitatory postsynapses of denervated dentate granule cells in vitro

Increased mortality in groups of cattle administered the β-adrenergic agonists ractopamine hydrochloride and zilpaterol hydrochloride

The United States Food and Drug Administration (FDA) approved two β-adrenergic agonists (βAA) for in-feed administration to cattle fed in confinement for human consumption. Anecdotal reports have generated concern that administration of βAA might be associated with an increased incidence of cattle deaths. Our objectives, therefore, were to a) quantify the association between βAA administration and mortality in feedlot cattle, and b) explore those variables that may confound or modify this association. Three datasets were acquired for analysis: one included information from randomized and controlled clinical trials of the βAA ractopamine hydrochloride, while the other two were observational data on zilpaterol hydrochloride administration to large numbers of cattle housed, fed, and cared for using routine commercial production practices in the U.S. Various population and time at-risk models were developed to explore potential βAA relationships with mortality, as well as the extent of confounding and effect modification. Measures of effect were relatively consistent across datasets and models in that the cumulative risk and incidence rate of death was 75 to 90% greater in animals administered the βAA compared to contemporaneous controls. During the exposure period, 40 to 50% of deaths among groups administered the βAA were attributed to administration of the drug. None of the available covariates meaningfully confounded the relationship between βAA and increased mortality. Only month of slaughter, presumably a proxy for climate, consistently modified the effect in that the biological association was generally greatest during the warmer months of the year. While death is a rare event in feedlot cattle, the data reported herein provide compelling evidence that mortality is nevertheless increased in response to administration of FDA-approved βAA and represents a heretofore unquantified adverse drug event

The highly cross-fertile coral species, Acropora hyacinthus and Acropora cytherea, constitute statistically distinguishable lineages

A major challenge for understanding the evolutionary genetics of mass-spawning corals is to explain the maintenance of discrete morphospecies in view of high rates of interspecific fertilization in vitro and nonmonophyletic patterns in molecular phylogenies. In this study, we focused on Acropora cytherea and A. hyacinthus, which have one of the highest potentials for interspecific fertilization. Using sequences of a nuclear intron, we performed phylogenetic and nested clade analyses (NCA). Both species were polyphyletic in molecular phylogenies, but the NCA indicated that they constitute statistically distinguishable lineages. Phylogenetic analysis using an intergenic region of the mitochondrial DNA (mtDNA), was inconclusive because of low levels of variability in this marker. The position of these two species differed between the nuclear DNA (nDNA) and mtDNA phylogenies and was also at odds with a cladistic analysis based on morphology. We conclude that despite the potential for high levels of hybridization and introgression, A. cytherea and A. hyacinthus constitute statistically distinguishable lineages and their taxonomic status is consistent with the cohesion species concept