Identification of medullary loci critical for neurogenesis of gasping

We hypothesized that a discrete medullary locus, critical for gasping neurogenesis, could be identified. In decerebrate, cerebellectomized, vagotomized, paralyzed, and ventilated cats, activities of phrenic, hypoglossal, and recurrent laryngeal nerves were monitored. Gasping was induced by freezing the brain stem, via a fork thermode, at the pontomedullary junction. By reversible cooling of the medulla, chemical lesions with kainic acid, and radio-frequency lesions, a critical area for gasping neurogenesis was localized bilaterally 2-3 mm rostral to obex, 2.0-2.5 mm lateral to midline, and 3-4 mm ventral to medullary surface. Electrical stimulation in this area elicited premature gasps, whereas unilateral lesions or lidocaine injections eliminated gasping activities in all nerves. These procedures did not cause similar changes during eupnea. In apneusis, however, lidocaine injections markedly altered the pattern or caused apnea. We conclude that discharge of neurons in a discrete portion of the lateral tegmental field of medulla is required for gasping neurogenesis. Our results are consistent with these neurons comprising the central pattern generator for gasping.     

DNA evolutionary rates in nine-primaried passerine birds

Differences in single-copy nuclear-DNA sequences among 13 species of passerine birds were measured using DNA-DNA hybridization. A matrix of pairwise dissimilarity values (delta mode distances) was constructed from analysis of fitted thermal dissociation curves. A least-squares method of phylogenetic estimation was used to construct two topologies from the distance matrix, one constraining branch lengths of sister taxa to be equal and the other permitting such lengths to vary. These topologies were identical in the pattern of branching of taxa, and the difference in their sums of squares was not statistically significant, suggesting that rates of DNA evolution in sister groups of nine- primaried oscines are equal. A nonparametric test for nonrandom variation in distances of sister groups to outgroup taxa revealed no statistically significant deviation from random variation that would be expected as a result of measurement error. However, the level of measurement error was such that rates of DNA evolution in sister taxa could vary by as much as 10% without being detected with the statistical methods used here.      

BOOTSTRAP CORRECTION FOR DIURNAL ACTIVITY CYCLE IN CENSUS DATA FOR ANTARCTIC SEALS1

Antarctic phocid seals and particularly the crabeater (Lobodon carcinophagus) have been observed to display a diurnal cycle in their propensity to haul out on pack ice where they are visible for census. The fact that they are not visible for much of the 24-h period means that density estimates made over broad geographic areas at various times of the day statistically confound this cycle with geographic variability. Limitation of census observations to times of peak haulout results in extreme logistical difficulties and/or considerable reduction in sample size upon which to base population estimates. Reduced sample size results in high variability in population estimates and broad confidence bands. To develop a model with which to correct density estimates for variability due to diurnal cycle, a series of stationary censuses at fixed locations in the Antarctic continental ice pack was made over significant fractions of several days. A unimodal polynomial model for the observed density variation in any one location was statistically significant; a similar model combining multiple locations with densities standardized to peak daily values was also significant. The latter model was used to make corrections for time of day to density estimates in three test data sets taken over broad geographic areas of the Antarctic. Statistical simulation (bootstrap) methods were used to determine if variances of corrected density estimates were lower than those based on uncorrected observations taken only during the peak haulout times of the day. Results were that 95% interval estimates for corrected densities were narrowed to between 40% and 61% of the uncorrected estimates. While there are additional possible sources of variation in haulout tendency, pending further data collection and analyses, the model developed represents a considerably more precise methodology than either averaging over haulout variability or limiting observations to peak daily periods.     

A quantitative assessment of congruence between molecular and nonmolecular estimates of phylogeny

Summary An important means of assessing the validity of phylogenetic hypotheses is to measure congruence between different studies of the same group. We applied statistical methods to assess patterns of congruence among phylogenies taken from the literature, using strict-consensus and quartet statistics to measure congruence for 48 pairs of phylogenies of various groups of birds and mammals. The strict-consensus measures were higher on average for distance-distance comparisons than for distance-parsimony or parsimony-parsimony comparisons, and for molecular-molecular comparisons than for molecular-morphological or morphological-morphological comparisons. However, the only factor that was consistently important statistically was the number of taxa involved in the comparison, with congruence decreasing as the number of taxa increased. Quartet indices, which measure network similarity regardless of root position, also showed an effect based on number of taxa but exhibited no trend toward higher congruence in molecular-molecular and distance-distance comparisons. The number of studies with jointly unresolved quartets was small, indicating that data sets varied in the degree to which they could resolve relationships at different phylogenetic levels.The levels of congruence between phylogenies, including those employing single-copy nuclear DNA hybridization data, appear to be higher than expected in random sets of trees, cannot be explained by nonindependence of data sets, and thus provide empirical support for the validity of both distance and parsimony methods of phylogenetic inference. In specific instances, low congruence pointed to mistakes in the application of certain methods, and to the existence of problem taxa in need of additional study.     

Disasters collide at the intersection of extreme weather and infectious diseases

Natural disasters interact to affect the resilience and prosperity of communities and disproportionately affect low income families and communities of colour. However, due to lack of a common theoretical framework, these are rarely quantified. Observing severe weather events (e.g. hurricanes and tornadoes) and epidemics (e.g. COVID-19) unfolding in southeastern US communities led us to conjecture that interactions among catastrophic disturbances might be much more considerable than previously recognized. For instance, hurricane evacuations increase human aggregation, a factor that affects the transmission of acute infections like SARS-CoV-2. Similarly, weather damage to health infrastructure can reduce a community's ability to provide services to people who are ill. As globalization and human population and movement continue to increase and weather events are becoming more intense, such complex interactions are expected to magnify and significantly impact environmental and human health.     

Behavioral budgets of captive sea otter mother–pup pairs during pup development

Instantaneous sampling of eight behavior categories for a captive mother sea otter (Enhydra lutris) and her four pups was conducted continuously during the first three months following each pup's birth. Initially, pup-grooming and rest occupied the largest proportion of the mother's time. Despite a steady decline in the amount of time the mother spent pup-grooming, the mother continued to groom the pup a substantial amount of time three months after the pup's birth. The proportion of time the mother spent resting, self-grooming, or swimming did not change significantly over the study period, suggesting that these behaviors are important to the mother's self-maintenance. The newborn pups' behaviors were initially limited to rest, active, and nursing, with large proportions of time spent resting and nursing. A significant increase in self-grooming occurred regularly by week 2, followed by increases in swimming (week 3), diving (week 6), and feeding (week 7). Three months after birth, the pups' behavior budgets were similar to their mother, with the exception that pups self-groomed substantially less than their mother self-groomed. The lower proportion of pup self-grooming may be due to the continued close proximity to their mother in captivity, which afforded extended association, and allowed the mother to continue to perform this complex behavior for the pup. © 1993 Wiley-Liss, Inc.     

A ligand-mediated hydrogen bond network required for the activation of the mineralocorticoid receptor

Ligand binding is the first step in hormone regulation of mineralocorticoid receptor (MR) activity. Here, we report multiple crystal structures of MR (NR3C2) bound to both agonist and antagonists. These structures combined with mutagenesis studies reveal that maximal receptor activation involves an intricate ligand-mediated hydrogen bond network with Asn770 which serves dual roles: stabilization of the loop preceding the C-terminal activation function-2 helix and direct contact with the hormone ligand. In addition, most activating ligands hydrogen bond to Thr945 on helix 10. Structural characterization of the naturally occurring S810L mutant explains how stabilization of a helix 3/helix 5 interaction can circumvent the requirement for this hydrogen bond network. Taken together, these results explain the potency of MR activation by aldosterone, the weak activation induced by progesterone and the antihypertensive agent spironolactone, and the binding selectivity of cortisol over cortisone.     

X-ray crystal structure of the liver X receptor beta ligand binding domain: regulation by a histidine-tryptophan switch

The x-ray crystal structures of the human liver X receptor beta ligand binding domain complexed to sterol and nonsterol agonists revealed a perpendicular histidinetryptophan switch that holds the receptor in its active conformation. Hydrogen bonding interactions with the ligand act to position the His-435 imidazole ring against the Trp-457 indole ring, allowing an electrostatic interaction that holds the AF2 helix in the active position. The neutral oxysterol 24(S),25-epoxycholesterol accepts a hydrogen bond from His-435 that positions the imidazole ring of the histidine above the pyrrole ring of the tryptophan. In contrast, the acidic T0901317 hydroxyl group makes a shorter hydrogen bond with His-435 that pulls the imidazole over the electron-rich benzene ring of the tryptophan, possibly strengthening the electrostatic interaction. Point mutagenesis of Trp-457 supports the observation that the ligand-histidine-tryptophan coupling is different between the two ligands. The lipophilic liver X receptor ligand-binding pocket is larger than the corresponding steroid hormone receptors, which allows T0901317 to adopt two distinct conformations. These results provide a molecular basis for liver X receptor activation by a wide range of endogenous neutral and acidic ligands.