The La Prele Mammoth Site, Converse County, Wyoming, USA

The La Prele Mammoth site is a Clovis archaeolog- ical site in Converse County, Wyoming (U.S.A.) that preserves chipped stone artifacts in spatial as- sociation with the remains of a subadult Columbi- an mammoth (Mammuthus columbi). The site was discovered in 1986 and initially tested by George Frison in 1987, but work ceased there until 2014 due to a disagreement with the landowner. In the intervening years, questions arose as to whether the artifacts and mammoth remains were truly associated, and the site was largely dismissed by American archaeologists. Recent excavations have not only demonstrated that La Prele was the loca- tion of a mammoth kill by Clovis hunters around 12,850 years ago, but it also preserves a campsite in close proximity to the kill. The camp includes multiple hearth-centered activity areas that appear to represent domestic spaces, reflected by the pres- ence of a diversity of stone tool forms, bone nee- dles, a bone bead, a large area of hematite-stained matrix, and the butchered and cooked remains of at least one other large mammal species. The site has the potential to inform us about aspects of the social organization of Clovis bands, particularly with respect to mammoth hunting and butchery.The symposium and the volume "Human-elephant interactions: from past to present" were funded by the Volkswagen Foundation

Natural variation and the capacity to adapt to ocean acidification in the keystone sea urchin Strongylocentrotus purpuratus

A rapidly growing body of literature documents the potential negative effects of CO2-driven ocean acidification (OA) on marine organisms. However, nearly all this work has focused on the effects of future conditions on modern populations, neglecting the role of adaptation. Rapid evolution can alter demographic responses to environmental change, ultimately affecting the likelihood of population persistence, but the capacity for adaptation will differ among populations and species. Here, we measure the capacity of the ecologically important purple sea urchin Strongylocentrotus purpuratus to adapt to OA, using a breeding experiment to estimate additive genetic variance for larval size (an important component of fitness) under future high-pCO2/low-pH conditions. Although larvae reared under future conditions were smaller than those reared under present-day conditions, we show that there is also abundant genetic variation for body size under elevated pCO2, indicating that this trait can evolve. The observed heritability of size was 0.40 ± 0.32 (95% CI) under low pCO2, and 0.50 ± 0.30 under high-pCO2 conditions. Accounting for the observed genetic variation in models of future larval size and demographic rates substantially alters projections of performance for this species in the future ocean. Importantly, our model shows that after incorporating the effects of adaptation, the OA-driven decrease in population growth rate is up to 50% smaller, than that predicted by the \u27no-adaptation\u27 scenario. Adults used in the experiment were collected from two sites on the coast of the Northeast Pacific that are characterized by different pH regimes, as measured by autonomous sensors. Comparing results between sites, we also found subtle differences in larval size under high-pCO2 rearing conditions, consistent with local adaptation to carbonate chemistry in the field. These results suggest that spatially varying selection may help to maintain genetic variation necessary for adaptation to future OA. © 2013 John Wiley & Sons Ltd

SUMO modification of the neuroprotective protein TDP1 facilitates chromosomal single-strand break repair

Breaking and sealing one strand of DNA is an inherent feature of chromosome metabolism to overcome torsional barriers. Failure to reseal broken DNA strands results in protein-linked DNA breaks, causing neurodegeneration in humans. This is typified by defects in tyrosyl DNA phosphodiesterase 1 (TDP1), which removes stalled topoisomerase 1 peptides from DNA termini. Here we show that TDP1 is a substrate for modification by the small ubiquitin-like modifier SUMO. We purify SUMOylated TDP1 from mammalian cells and identify the SUMOylation site as lysine 111. While SUMOylation exhibits no impact on TDP1 catalytic activity, it promotes its accumulation at sites of DNA damage. A TDP1 SUMOylation-deficient mutant displays a reduced rate of repair of chromosomal single-strand breaks arising from transcription-associated topoisomerase 1 activity or oxidative stress. These data identify a role for SUMO during single-strand break repair, and suggest a mechanism for protecting the nervous system from genotoxic stress

The DSM diagnostic criteria for female orgasmic disorder

This is the post-print version of the article. The official published version can be found at the link below.This article reviews the DSM diagnostic criteria for Female Orgasmic Disorder (FOD). Following an overview of the concept of female orgasm, research on the prevalence and associated features of FOD is briefly reviewed. Specific aspects of the DSM-IV-TR criteria for FOD are critically reviewed and key issues that should be considered for DSM-V are discussed. The DSM-IV-TR text on FOD focused on the physiological changes that may (or may not) accompany orgasm in women; one of the major recommendations here is that greater emphasis be given to the subjective aspects of the experience of orgasm. Additional specific recommendations are made for revision of diagnostic criteria, including the use of minimum severity and duration criteria, and better acknowledgment of the crucial role of relationship factors in FOD

Comparing proton momentum distributions in A=2A=2 and 3 nuclei via 2^2H 3^3H and 3^3He (e,e′p)(e, e'p) measurements

We report the first measurement of the $(e,e'p)$ reaction cross-section ratios for Helium-3 ($^3$He), Tritium ($^3$H), and Deuterium ($d$). The measurement covered a missing momentum range of $40 \le p_{miss} \le 550$ MeV$/c$, at large momentum transfer ($\langle Q^2 \rangle \approx 1.9$ (GeV$/c$)$^2$) and $x_B>1$, which minimized contributions from non quasi-elastic (QE) reaction mechanisms. The data is compared with plane-wave impulse approximation (PWIA) calculations using realistic spectral functions and momentum distributions. The measured and PWIA-calculated cross-section ratios for $^3$He$/d$ and $^3$H$/d$ extend to just above the typical nucleon Fermi-momentum ($k_F \approx 250$ MeV$/c$) and differ from each other by $\sim 20\%$, while for $^3$He/$^3$H they agree within the measurement accuracy of about 3\%. At momenta above $k_F$, the measured $^3$He/$^3$H ratios differ from the calculation by $20\% - 50\%$. Final state interaction (FSI) calculations using the generalized Eikonal Approximation indicate that FSI should change the $^3$He/$^3$H cross-section ratio for this measurement by less than 5\%. If these calculations are correct, then the differences at large missing momenta between the $^3$He/$^3$H experimental and calculated ratios could be due to the underlying $NN$ interaction, and thus could provide new constraints on the previously loosely-constrained short-distance parts of the $NN$ interaction.Comment: 8 pages, 3 figures (4 panels

Predicting spring phenology in deciduous broadleaf forests: NEON phenology forecasting community challenge

480181-19C90 - Virginia Polytechinic Institute and State University; National Science FoundationPublished versio

Niemann-Pick disease type C

Niemann-Pick C disease (NP-C) is a neurovisceral atypical lysosomal lipid storage disorder with an estimated minimal incidence of 1/120 000 live births. The broad clinical spectrum ranges from a neonatal rapidly fatal disorder to an adult-onset chronic neurodegenerative disease. The neurological involvement defines the disease severity in most patients but is typically preceded by systemic signs (cholestatic jaundice in the neonatal period or isolated spleno- or hepatosplenomegaly in infancy or childhood). The first neurological symptoms vary with age of onset: delay in developmental motor milestones (early infantile period), gait problems, falls, clumsiness, cataplexy, school problems (late infantile and juvenile period), and ataxia not unfrequently following initial psychiatric disturbances (adult form). The most characteristic sign is vertical supranuclear gaze palsy. The neurological disorder consists mainly of cerebellar ataxia, dysarthria, dysphagia, and progressive dementia. Cataplexy, seizures and dystonia are other common features. NP-C is transmitted in an autosomal recessive manner and is caused by mutations of either the NPC1 (95% of families) or the NPC2 genes. The exact functions of the NPC1 and NPC2 proteins are still unclear. NP-C is currently described as a cellular cholesterol trafficking defect but in the brain, the prominently stored lipids are gangliosides. Clinical examination should include comprehensive neurological and ophthalmological evaluations. The primary laboratory diagnosis requires living skin fibroblasts to demonstrate accumulation of unesterified cholesterol in perinuclear vesicles (lysosomes) after staining with filipin. Pronounced abnormalities are observed in about 80% of the cases, mild to moderate alterations in the remainder ("variant" biochemical phenotype). Genotyping of patients is useful to confirm the diagnosis in the latter patients and essential for future prenatal diagnosis. The differential diagnosis may include other lipidoses; idiopathic neonatal hepatitis and other causes of cholestatic icterus should be considered in neonates, and conditions with cerebellar ataxia, dystonia, cataplexy and supranuclear gaze palsy in older children and adults. Symptomatic management of patients is crucial. A first product, miglustat, has been granted marketing authorization in Europe and several other countries for specific treatment of the neurological manifestations. The prognosis largely correlates with the age at onset of the neurological manifestations

Exome-wide Rare Variant Analysis Identifies TUBA4A Mutations Associated with Familial ALS

Exome sequencing is an effective strategy for identifying human disease genes. However, this methodology is difficult in late-onset diseases where limited availability of DNA from informative family members prohibits comprehensive segregation analysis. To overcome this limitation, we performed an exome-wide rare variant burden analysis of 363 index cases with familial ALS (FALS). The results revealed an excess of patient variants within TUBA4A, the gene encoding the Tubulin, Alpha 4A protein. Analysis of a further 272 FALS cases and 5,510 internal controls confirmed the overrepresentation as statistically significant and replicable. Functional analyses revealed that TUBA4A mutants destabilize the microtubule network, diminishing its repolymerization capability. These results further emphasize the role of cytoskeletal defects in ALS and demonstrate the power of gene-based rare variant analyses in situations where causal genes cannot be identified through traditional segregation analysis