Male mastodon landscape use changed with maturation (late Pleistocene, North America)

Under harsh Pleistocene climates, migration and other forms of seasonally patterned landscape use were likely critical for reproductive success of mastodons (Mammut americanum) and other megafauna. However, little is known about how their geographic ranges and mobility fluctuated seasonally or changed with sexual maturity. We used a spatially explicit movement model that coupled strontium and oxygen isotopes from two serially sampled intervals (5+ adolescent years and 3+ adult years) in a male mastodon tusk to test for changes in landscape use associated with maturation and reproductive phenology. The mastodon’s early adolescent home range was geographically restricted, with no evidence of seasonal preferences. Following inferred separation from the matriarchal herd (starting age 12 y), the adolescent male’s mobility increased as landscape use expanded away from his natal home range (likely central Indiana). As an adult, the mastodon’s monthly movements increased further. Landscape use also became seasonally structured, with some areas, including northeast Indiana, used only during the inferred mastodon mating season (spring/summer). The mastodon died in this area (\u3e150 km from his core, nonsummer range) after sustaining a craniofacial injury consistent with a fatal blow from a competing male’s tusk during a battle over access to mates. Northeast Indiana was likely a preferred mating area for this individual and may have been regionally significant for late Pleistocene mastodons. Similarities between mammutids and elephantids in herd structure, tusk dimorphism, tusk function, and the geographic component of male maturation indicate that these traits were likely inherited from a common ancestor

Editorial: A Golden Age for Strontium Isotope Research? Current Advances in Paleoecological and Archaeological Research

Peer reviewedPublisher PD

Silver Linings at the Dawn of a ‘Golden Age'

ACKNOWLEDGMENTS We would like to thank the editors at Frontiers for their support and patience, and the careful consideration two reviewers gave to this manuscript. MJW would like to acknowledge that, at Fairbanks, he is working on the ancestral land of Troth Yeddha’, home of the Lower Tanana people. He would also like to acknowledge that the lands on which he does his work are the ancestral lands of the Dené people who stewarded those lands for thousands of years and continue to steward those lands, further he would like to thank them and respect their enduring relationship to their homelands.Peer reviewedPublisher PD

Comparing the paleoclimates of northwestern and southwestern Madagascar during the late Holocene: Implications for the role of climate in megafaunal extinction.

The relative importance of climate and humans in the disappearance of the Malagasy megafauna remains under debate. Data from southwestern Madagascar imply aridifcation contributed substantially to the late Holocene decline of the megafauna (the Aridifcation Hypothesis). Evidence for aridifcation includes carbon isotopes from tree rings, lacustrine charcoal concentrations and pollen assemblages, and changes in fossil vertebrate assemblages indicative of a local loss of pluvial conditions. In contrast, speleothem records from northwestern Madagascar suggest that megafaunal decline and habitat change resulted primarily from human activity including agropastoralism (the Subsistence Shift Hypothesis). Could there have been contrasting mechanisms of decline in different parts of Madagascar? Or are we lacking the precisely dated, high resolution records needed to fully understand the complex processes behind megafaunal decline? Reconciling these contrasting hypotheses requires additional climate records from southwestern Madagascar. We recovered a stalagmite (AF2) from Asafora Cave in the spiny thicket ecoregion, ~10 km from the southwest coast and just southeast of the Velondriake Marine Reserve. U-series and 14C dating of samples taken from the core of this stalagmite provide a highly precise chronology of the changes in hydroclimate and vegetation in this region over the past 3000 years. Speleothem stable oxygen and carbon isotope analyses provide insight into past rainfall variability and vegetation changes respectively. We compare these records with those for a stalagmite (AB2) from Anjohibe Cave in northwestern Madagascar. Lastly, odds ratio analyses of radiocarbon dates for extinct and extant subfossils allow us to describe and compare the temporal trajectories of megafaunal decline in the southwest and the northwest. Combined, these analyses allow us to test the Aridifcation Hypothesis for megafaunal extinction. The trajectories of megafaunal decline differed in northwestern and southwestern Madagascar. In the southwest, unlike the northwest, there is no evidence of decoupling of speleothem stable carbon and oxygen isotopes. Instead, habitat changes in the southwest were largely related to variation in hydroclimate (including a prolonged drought). The megafaunal collapse here occurred in tandem with the drought, and agropastoralism likely contributed to that demise only after the megafauna had already suffered drought-related population reduction. Our results offer some support for the Aridifcation Hypothesis, but with three caveats: frst, that there was no island-wide aridifcation; second, that aridifcation likely impacted megafaunal decline only in the driest parts of Madagascar; and third, that aridifcation was not the sole factor promoting Comparing the paleoclimates of northwestern and southwestern Madagascar during the late Holocene: Implications for the role of climate in megafaunal extinction Faina et al.: Comparing the paleoclimates of northwestern and southwestern Madagascar 109 megafaunal decline even in the dry southwest. A number of megafaunal species survived the prolonged drought of the first millennium, and then likely succumbed to the activities of agropastoralists

Quantitative trait locus analysis identifies Gabra3 as a regulator of behavioral despair in mice

The Tail Suspension Test (TST), which measures behavioral despair, is widely used as an animal model of human depressive disorders and antidepressant efficacy. In order to identify novel genes involved in the regulation of TST performance, we crossed an inbred strain exhibiting low immobility in the TST (RIIIS/J) with two high-immobility strains (C57BL/6J and NZB/BlNJ) to create two distinct F2 hybrid populations. All F2 offspring (n = 655) were genotyped at high density with a panel of SNP markers. Whole-genome interval mapping of the F2 populations identified statistically significant quantitative trait loci (QTLs) on mouse chromosomes (MMU) 4, 6, and X. Microarray analysis of hippocampal gene expression in the three parental strains was used to identify potential candidate genes within the MMUX QTLs identified in the NZB/BlNJ × RIIIS/J cross. Expression of Gabra3, which encodes the GABAA receptor α3 subunit, was robust in the hippocampus of B6 and RIIIS mice but absent from NZB hippocampal tissue. To verify the role of Gabra3 in regulating TST behavior in vivo, mice were treated with SB-205384, a positive modulator of the α3 subunit. SB-205384 significantly reduced TST immobility in B6 mice without affecting general activity, but it had no effect on behavior in NZB mice. This work suggests that GABRA3 regulates a behavioral endophenotype of depression and establishes this gene as a viable new target for the study and treatment of human depression

Stable carbon and nitrogen isotope enrichment in primate tissues

Isotopic studies of wild primates have used a wide range of tissues to infer diet and model the foraging ecologies of extinct species. The use of mismatched tissues for such comparisons can be problematic because differences in amino acid compositions can lead to small isotopic differences between tissues. Additionally, physiological and dietary differences among primate species could lead to variable offsets between apatite carbonate and collagen. To improve our understanding of the isotopic chemistry of primates, we explored the apparent enrichment (ε*) between bone collagen and muscle, collagen and fur or hair keratin, muscle and keratin, and collagen and bone carbonate across the primate order. We found that the mean ε* values of proteinaceous tissues were small (≤1‰), and uncorrelated with body size or phylogenetic relatedness. Additionally, ε* values did not vary by habitat, sex, age, or manner of death. The mean ε* value between bone carbonate and collagen (5.6 ± 1.2‰) was consistent with values reported for omnivorous mammals consuming monoisotopic diets. These primate-specific apparent enrichment values will be a valuable tool for cross-species comparisons. Additionally, they will facilitate dietary comparisons between living and fossil primates

Phenotypic Characterization of a Genetically Diverse Panel of Mice for Behavioral Despair and Anxiety

Animal models of human behavioral endophenotypes, such as the Tail Suspension Test (TST) and the Open Field assay (OF), have proven to be essential tools in revealing the genetics and mechanisms of psychiatric diseases. As in the human disorders they model, the measurements generated in these behavioral assays are significantly impacted by the genetic background of the animals tested. In order to better understand the strain-dependent phenotypic variability endemic to this type of work, and better inform future studies that rely on the data generated by these models, we phenotyped 33 inbred mouse strains for immobility in the TST, a mouse model of behavioral despair, and for activity in the OF, a model of general anxiety and locomotor activity.We identified significant strain-dependent differences in TST immobility, and in thigmotaxis and distance traveled in the OF. These results were replicable over multiple testing sessions and exhibited high heritability. We exploited the heritability of these behavioral traits by using in silico haplotype-based association mapping to identify candidate genes for regulating TST behavior. Two significant loci (-logp >7.0, gFWER adjusted p value <0.05) of approximately 300 kb each on MMU9 and MMU10 were identified. The MMU10 locus is syntenic to a major human depressive disorder QTL on human chromosome 12 and contains several genes that are expressed in brain regions associated with behavioral despair.We report the results of phenotyping a large panel of inbred mouse strains for depression and anxiety-associated behaviors. These results show significant, heritable strain-specific differences in behavior, and should prove to be a valuable resource for the behavioral and genetics communities. Additionally, we used haplotype mapping to identify several loci that may contain genes that regulate behavioral despair

Evaluating genetic markers and neurobiochemical analytes for fluoxetine response using a panel of mouse inbred strains

RationaleIdentification of biomarkers that establish diagnosis or treatment response is critical to the advancement of research and management of patients with depression.ObjectiveOur goal was to identify biomarkers that can potentially assess fluoxetine response and risk to poor treatment outcome.MethodsWe measured behavior, gene expression, and the levels of 36 neurobiochemical analytes across a panel of genetically diverse mouse inbred lines after chronic treatment with water or fluoxetine.ResultsGlyoxylase 1 (GLO1) and guanine nucleotide-binding protein 1 (GNB1) mostly account for baseline anxiety-like and depressive-like behavior, indicating a common biological link between depression and anxiety. Fluoxetine-induced biochemical alterations discriminated positive responders, while baseline neurobiochemical differences differentiated negative responders (p < 0.006). Results show that glial fibrillary acidic protein, S100 beta protein, GLO1, and histone deacetylase 5 contributed most to fluoxetine response. These proteins are linked within a cellular growth/proliferation pathway, suggesting the involvement of cellular genesis in fluoxetine response. Furthermore, a candidate genetic locus that associates with baseline depressive-like behavior contains a gene that encodes for cellular proliferation/adhesion molecule (Cadm1), supporting a genetic basis for the role of neuro/gliogenesis in depression.ConclusionWe provided a comprehensive analysis of behavioral, neurobiochemical, and transcriptome data across 30 mouse inbred strains that has not been accomplished before. We identified biomarkers that influence fluoxetine response, which, altogether, implicate the importance of cellular genesis in fluoxetine treatment. More broadly, this approach can be used to assess a wide range of drug response phenotypes that are challenging to address in human samples.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-011-2574-z) contains supplementary material, which is available to authorized users

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease