Correlations Between Life-Detection Techniques and Implications for Sampling Site Selection in Planetary Analog Missions

We conducted an analog sampling expedition under simulated mission constraints to areas dominated by basaltic tephra of the Eldfell and Fimmvorouhals lava fields (Iceland). Sites were selected to be homogeneous at a coarse remote sensing resolution (10-100m) in apparent color, morphology, moisture, and grain size, with best-effort realism in numbers of locations and replicates. Three different biomarker assays (counting of nucleic-acid-stained cells via fluorescent microscopy, a luciferin/luciferase assay for adenosine triphosphate, and quantitative polymerase chain reaction (qPCR) to detect DNA associated with bacteria, archaea, and fungi) were characterized at four nested spatial scales (1m, 10m, 100m, and >1km) by using five common metrics for sample site representativeness (sample mean variance, group F tests, pairwise t tests, and the distribution-free rank sum H and u tests). Correlations between all assays were characterized with Spearman's rank test. The bioluminescence assay showed the most variance across the sites, followed by qPCR for bacterial and archaeal DNA; these results could not be considered representative at the finest resolution tested (1m). Cell concentration and fungal DNA also had significant local variation, but they were homogeneous over scales of >1km. These results show that the selection of life detection assays and the number, distribution, and location of sampling sites in a low biomass environment with limited a priori characterization can yield both contrasting and complementary results, and that their interdependence must be given due consideration to maximize science return in future biomarker sampling expeditions. Key Words: AstrobiologyBiodiversityMicrobiologyIcelandPlanetary explorationMars mission simulationBiomarker. Astrobiology 17, 1009-1021

Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU

Stem cells are proposed to segregate chromosomes asymmetrically during self-renewing divisions so that older ('immortal') DNA strands are retained in daughter stem cells whereas newly synthesized strands segregate to differentiating cells(1-6). Stem cells are also proposed to retain DNA labels, such as 5-bromo-2-deoxyuridine (BrdU), either because they segregate chromosomes asymmetrically or because they divide slowly(5,7-9). However, the purity of stem cells among BrdU-label-retaining cells has not been documented in any tissue, and the 'immortal strand hypothesis' has not been tested in a system with definitive stem cell markers. Here we tested these hypotheses in haematopoietic stem cells (HSCs), which can be highly purified using well characterized markers. We administered BrdU to newborn mice, mice treated with cyclophosphamide and granulocyte colony-stimulating factor, and normal adult mice for 4 to 10 days, followed by 70 days without BrdU. In each case, less than 6% of HSCs retained BrdU and less than 0.5% of all BrdU-retaining haematopoietic cells were HSCs, revealing that BrdU has poor specificity and poor sensitivity as an HSC marker. Sequential administration of 5-chloro-2-deoxyuridine and 5-iodo-2-deoxyuridine indicated that all HSCs segregate their chromosomes randomly. Division of individual HSCs in culture revealed no asymmetric segregation of the label. Thus, HSCs cannot be identified on the basis of BrdU-label retention and do not retain older DNA strands during division, indicating that these are not general properties of stem cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62821/1/nature06115.pd

Variation in LPA Is Associated with Lp(a) Levels in Three Populations from the Third National Health and Nutrition Examination Survey

The distribution of lipoprotein(a) [Lp(a)] levels can differ dramatically across diverse racial/ethnic populations. The extent to which genetic variation in LPA can explain these differences is not fully understood. To explore this, 19 LPA tagSNPs were genotyped in 7,159 participants from the Third National Health and Nutrition Examination Survey (NHANES III). NHANES III is a diverse population-based survey with DNA samples linked to hundreds of quantitative traits, including serum Lp(a). Tests of association between LPA variants and transformed Lp(a) levels were performed across the three different NHANES subpopulations (non-Hispanic whites, non-Hispanic blacks, and Mexican Americans). At a significance threshold of p<0.0001, 15 of the 19 SNPs tested were strongly associated with Lp(a) levels in at least one subpopulation, six in at least two subpopulations, and none in all three subpopulations. In non-Hispanic whites, three variants were associated with Lp(a) levels, including previously known rs6919246 (p = 1.18×10−30). Additionally, 12 and 6 variants had significant associations in non-Hispanic blacks and Mexican Americans, respectively. The additive effects of these associated alleles explained up to 11% of the variance observed for Lp(a) levels in the different racial/ethnic populations. The findings reported here replicate previous candidate gene and genome-wide association studies for Lp(a) levels in European-descent populations and extend these findings to other populations. While we demonstrate that LPA is an important contributor to Lp(a) levels regardless of race/ethnicity, the lack of generalization of associations across all subpopulations suggests that specific LPA variants may be contributing to the observed Lp(a) between-population variance

Entrepreneurs, Chance, and the Deterministic Concentration of Wealth

In many economies, wealth is strikingly concentrated. Entrepreneurs–individuals with ownership in for-profit enterprises–comprise a large portion of the wealthiest individuals, and their behavior may help explain patterns in the national distribution of wealth. Entrepreneurs are less diversified and more heavily invested in their own companies than is commonly assumed in economic models. We present an intentionally simplified individual-based model of wealth generation among entrepreneurs to assess the role of chance and determinism in the distribution of wealth. We demonstrate that chance alone, combined with the deterministic effects of compounding returns, can lead to unlimited concentration of wealth, such that the percentage of all wealth owned by a few entrepreneurs eventually approaches 100%. Specifically, concentration of wealth results when the rate of return on investment varies by entrepreneur and by time. This result is robust to inclusion of realities such as differing skill among entrepreneurs. The most likely overall growth rate of the economy decreases as businesses become less diverse, suggesting that high concentrations of wealth may adversely affect a country's economic growth. We show that a tax on large inherited fortunes, applied to a small portion of the most fortunate in the population, can efficiently arrest the concentration of wealth at intermediate levels

Snarky Signatures: Minimal Signatures of Knowledge from Simulation-Extractable SNARKs

We construct a pairing based simulation-extractable SNARK (SE-SNARK) that consists of only 3 group elements and has highly efficient verification. By formally linking SE-SNARKs to signatures of knowledge, we then obtain a succinct signature of knowledge consisting of only 3 group elements. SE-SNARKs enable a prover to give a proof that they know a witness to an instance in a manner which is: (1) succinct - proofs are short and verifier computation is small; (2) zero-knowledge - proofs do not reveal the witness; (3) simulation-extractable - it is only possible to prove instances to which you know a witness, even when you have already seen a number of simulated proofs. We also prove that any pairing based signature of knowledge or SE-NIZK argument must have at least 3 group elements and 2 verification equations. Since our constructions match these lower bounds, we have the smallest size signature of knowledge and the smallest size SE-SNARK possible

The p75 neurotrophin receptor is expressed by adult mouse dentate progenitor cells and regulates neuronal and non-neuronal cell genesis

<p>Abstract</p> <p>Background</p> <p>The ability to regulate neurogenesis in the adult dentate gyrus will require further identification and characterization of the receptors regulating this process. <it>In vitro </it>and <it>in vivo </it>studies have demonstrated that neurotrophins and the p75 neurotrophin receptor (p75^NTR) can promote neurogenesis; therefore we tested the hypothesis that p75^NTRis expressed by adult dentate gyrus progenitor cells and is required for their proliferation and differentiation.</p> <p>Results</p> <p>In a first series of studies focusing on proliferation, mice received a single BrdU injection and were sacrificed 2, 10 and 48 hours later. Proliferating, BrdU-positive cells were found to express p75^NTR. In a second series of studies, BrdU was administered by six daily injections and mice were sacrificed 1 day later. Dentate gyrus sections demonstrated a large proportion of BrdU/p75^NTRco-expressing cells expressing either the NeuN neuronal or GFAP glial marker, indicating that p75^NTRexpression persists at least until early stages of maturation. In p75^NTR(-/-) mice, there was a 59% decrease in the number of BrdU-positive cells, with decreases in the number of BrdU cells co-labeled with NeuN, GFAP or neither marker of 35%, 60% and 64%, respectively.</p> <p>Conclusions</p> <p>These findings demonstrate that p75^NTRis expressed by adult dentate progenitor cells and point to p75^NTRas an important receptor promoting the proliferation and/or early maturation of not only neural, but also glial and other cell types.</p

Molecular phylogenetics reveal multiple tertiary vicariance origins of the African rain forest trees

Background - Tropical rain forests are the most diverse terrestrial ecosystems on the planet. How this diversity evolved remains largely unexplained. In Africa, rain forests are situated in two geographically isolated regions: the West-Central Guineo-Congolian region and the coastal and montane regions of East Africa. These regions have strong floristic affinities with each other, suggesting a former connection via an Eocene pan-African rain forest. High levels of endemism observed in both regions have been hypothesized to be the result of either 1) a single break-up followed by a long isolation or 2) multiple fragmentation and reconnection since the Oligocene. To test these hypotheses the evolutionary history of endemic taxa within a rain forest restricted African lineage of the plant family Annonaceae was studied. Molecular phylogenies and divergence dates were estimated using a Bayesian relaxed uncorrelated molecular clock assumption accounting for both calibration and phylogenetic uncertainties. Results - Our results provide strong evidence that East African endemic lineages of Annonaceae have multiple origins dated to significantly different times spanning the Oligocene and Miocene epochs. Moreover, these successive origins (c. 33, 16 and 8 million years ¿ Myr) coincide with known periods of aridification and geological activity in Africa that would have recurrently isolated the Guineo-Congolian rain forest from the East African one. All East African taxa were found to have diversified prior to Pleistocene times. Conclusion - Molecular phylogenetic dating analyses of this large pan-African clade of Annonaceae unravels an interesting pattern of diversification for rain forest restricted trees co-occurring in West/Central and East African rain forests. Our results suggest that repeated reconnections between the West/Central and East African rain forest blocks allowed for biotic exchange while the break-ups induced speciation via vicariance, enhancing the levels of endemicity. These results provide an explanation for present day distribution patterns and origins of endemicity for African rain forest trees. Moreover, given the pre-Pleistocene origins of all the studied endemic East African genera and species, these results also offer important insights for setting conservation priorities in these highly diversified but threatene

Selective blockade of interferon-α and -β reveals their non-redundant functions in a mouse model of West Nile virus infection

Although type I interferons (IFNs) were first described almost 60 years ago, the ability to monitor and modulate the functional activities of the individual IFN subtypes that comprise this family has been hindered by a lack of reagents. The major type I IFNs, IFN-β and the multiple subtypes of IFN-α, are expressed widely and induce their effects on cells by interacting with a shared heterodimeric receptor (IFNAR). In the mouse, the physiologic actions of IFN-α and IFN-β have been defined using polyclonal anti-type I IFN sera, by targeting IFNAR using monoclonal antibodies or knockout mice, or using Ifnb-/- mice. However, the corresponding analysis of IFN-α has been difficult because of its polygenic nature. Herein, we describe two monoclonal antibodies (mAbs) that differentially neutralize murine IFN-β or multiple subtypes of murine IFN-α. Using these mAbs, we distinguish specific contributions of IFN-β versus IFN-α in restricting viral pathogenesis and identify IFN-α as the key mediator of the antiviral response in mice infected with West Nile virus. This study thus suggests the utility of these new reagents in dissecting the antiviral and immunomodulatory roles of IFN-β versus IFN-α in murine models of infection, immunity, and autoimmunity

Paleodistributions and Comparative Molecular Phylogeography of Leafcutter Ants (Atta spp.) Provide New Insight into the Origins of Amazonian Diversity

The evolutionary basis for high species diversity in tropical regions of the world remains unresolved. Much research has focused on the biogeography of speciation in the Amazon Basin, which harbors the greatest diversity of terrestrial life. The leading hypotheses on allopatric diversification of Amazonian taxa are the Pleistocene refugia, marine incursion, and riverine barrier hypotheses. Recent advances in the fields of phylogeography and species-distribution modeling permit a modern re-evaluation of these hypotheses. Our approach combines comparative, molecular phylogeographic analyses using mitochondrial DNA sequence data with paleodistribution modeling of species ranges at the last glacial maximum (LGM) to test these hypotheses for three co-distributed species of leafcutter ants (Atta spp.). The cumulative results of all tests reject every prediction of the riverine barrier hypothesis, but are unable to reject several predictions of the Pleistocene refugia and marine incursion hypotheses. Coalescent dating analyses suggest that population structure formed recently (Pleistocene-Pliocene), but are unable to reject the possibility that Miocene events may be responsible for structuring populations in two of the three species examined. The available data therefore suggest that either marine incursions in the Miocene or climate changes during the Pleistocene—or both—have shaped the population structure of the three species examined. Our results also reconceptualize the traditional Pleistocene refugia hypothesis, and offer a novel framework for future research into the area