Solutrean hypothesis: genetics, the mammoth in the room

© 2014 Taylor & Francis. This is an Accepted Manuscript of an article published by Taylor & Francis Group in World Archaeology on 31/10/2014, available online: http://www.tandfonline.com/10.1080/00438243.2014.966273.The Solutrean Hypothesis for the origin of the Clovis archaeological culture has received numerous challenges and critiques. Oft-repeated contra-assertions, predominantly from archaeologists, range from: “NO genetic evidence”, to: it must have been either a sole Beringian or European origin, so Beringia wins, to: the troublesome fifth American mtDNA lineage “X2a” overlanded from West-Eurasia to Beringia, leaving no trace en-route, to: there is no evidence from the rest of the genome to parallel X2a. We refute these contra-assertions, detailing published contrary evidence, supporting a West-Eurasian origin for some Native American ancestors, mainly found in north-eastern America, in parallel to the majority arriving from Beringia. Specifically this includes mtDNA-X2a found in ancient and modern Native American populations, with no evidence to support migration of X2a through Siberia. Prima facie (i.e. under-researched) published evidence also exists for equivalent levels of West-Eurasian Y-chromosomes and autosomal markers in the same regions

SeaWiFS Technical Report Series

The Sea-viewing Wide Field-of-view Sensor (SeaWiFS) mission will provide operational ocean color that will be superior to the previous Coastal Zone Color Sensor (CZCS) proof-of-concept mission. An algorithm is needed that exploits the full functionality of SeaWiFS whilst remaining compatible in concept with algorithms used for the CZCS. This document describes the theoretical rationale of radiance band-ratio methods for determining chlorophyll-a and other important biogeochemical parameters, and their implementation for the SeaWIFS mission. Pigment interrelationships are examined to explain the success of the CZCS algorithms. In the context where chlorophyll-a absorbs only weakly at 520 nm, the success of the 520 nm to 550 nm CZCS band ratio needs to be explained. This is explained by showing that in pigment data from a range of oceanic provinces chlorophyll-a (absorbing at less than 490 nm), carotenoids (absorbing at greater than 460 nm), and total pigment are highly correlated. Correlations within pigment groups particularly photoprotectant and photosynthetic carotenoids are less robust. The sources of variability in optical data are examined using the NIMBUS Experiment Team (NET) bio-optical data set and bio-optical model. In both the model and NET data, the majority of the variance in the optical data is attributed to variability in pigment (chlorophyll-a), and total particulates, with less than 5% of the variability resulting from pigment assemblage. The relationships between band ratios and chlorophyll is examined analytically, and a new formulation based on a dual hyperbolic model is suggested which gives a better calibration curve than the conventional log-log linear regression fit. The new calibration curve shows the 490:555 ratio is the best single-band ratio and is the recommended CZCS-type pigment algorithm. Using both the model and NET data, a number of multiband algorithms are developed; the best of which is an algorithm based on the 443:555 and 490:555 ratios. From model data, the form of potential algorithms for other products, such as total particulates and dissolved organic matter (DOM), are suggested

SeaWiFS Technical Report Series. Volume 29: SeaWiFS CZCS-type pigment algorithm

The Sea-viewing Wide Field-of-view Sensor (SeaWiFS) mission will provide operational ocean color that will be superior to the previous Coastal Zone Color Sensor (CZCS) proof-of-concept mission. an algorithm is needed that exploits the full functionality of SeaWiFS whilst remaining compatible in concept with algorithms used for the CZCS. This document describes the theoretical rationale of radiance band-radio methods for determining chlorophyll alpha and other important biogeochemical parameters, and their implementation for the SeaWiFS mission. Pigment interrelationships are examined to explain the success of the CZCS algorithms. In the context where chlorophyll alpha absorbs only weakly at 520 nm, the success of the 520 nm to 550 nm CZCS band ratio needs to be explained. This is explained by showing that in pigment data from a range of oceanic provinces chlorophyll alpha (absorbing at less than 490 nm), carotenoids (absorbing at greater than 460 nm), and total pigment are highly correlated. Correlations within pigment groups particularly photoprotectant and photosynthetic carotenoids are less robust. The sources of variability in optical data re examined using the NIMBUS Experiment Team (NET) bio-optical data set and bio-optical model. In both the model and NET data, the majority of the variance in the optical data is attributed to variability in pigment (chlorophyll alpha, and total particulates, with less than 5% of the variability resulting from pigment assemblage. The relationships between band ratios and chlorophyll is examined analytically, and a new formulation based on a dual hyperbolic model is suggested which gives a better calibration curve than the conventional log-log linear regression fit. The new calibration curve shows that 490:555 ratio is the best single-band ratio and is the recommended CZCS-type pigment algorithm. Using both the model and NET data, a number of multiband algorithms are developed; the best of which is an algorithm based on the 443:555 and 490:555 ratios. From model data, the form of potential algorithms for other products, such as total particulates and dissolved organic matter (DOM), are suggested

The Multi-Epoch Nearby Cluster Survey: type Ia supernova rate measurement in z~0.1 clusters and the late-time delay time distribution

We describe the Multi-Epoch Nearby Cluster Survey (MENeaCS), designed to measure the cluster Type Ia supernova (SN Ia) rate in a sample of 57 X-ray selected galaxy clusters, with redshifts of 0.05 < z < 0.15. Utilizing our real time analysis pipeline, we spectroscopically confirmed twenty-three cluster SN Ia, four of which were intracluster events. Using our deep CFHT/Megacam imaging, we measured total stellar luminosities in each of our galaxy clusters, and we performed detailed supernova detection efficiency simulations. Bringing these ingredients together, we measure an overall cluster SN Ia rate within R_{200} (1 Mpc) of 0.042^{+0.012}_{-0.010}^{+0.010}_{-0.008} SNuM (0.049^{+0.016}_{-0.014}^{+0.005}_{-0.004} SNuM) and a SN Ia rate within red sequence galaxies of 0.041^{+0.015}_{-0.015}^{+0.005}_{-0.010} SNuM (0.041^{+0.019}_{-0.015}^{+0.005}_{-0.004} SNuM). The red sequence SN Ia rate is consistent with published rates in early type/elliptical galaxies in the `field'. Using our red sequence SN Ia rate, and other cluster SNe measurements in early type galaxies up to $z\sim1$, we derive the late time (>2 Gyr) delay time distribution (DTD) of SN Ia assuming a cluster early type galaxy star formation epoch of z_f=3. Assuming a power law form for the DTD, \Psi(t)\propto t^s, we find s=-1.62\pm0.54. This result is consistent with predictions for the double degenerate SN Ia progenitor scenario (s\sim-1), and is also in line with recent calculations for the double detonation explosion mechanism (s\sim-2). The most recent calculations of the single degenerate scenario delay time distribution predicts an order of magnitude drop off in SN Ia rate \sim 6-7 Gyr after stellar formation, and the observed cluster rates cannot rule this out.Comment: 35 pages, 14 figures, ApJ accepte

High-throughput screen using a single-cell tyrosine phosphatase assay reveals biologically active inhibitors of tyrosine phosphatase CD45

Many cellular signaling events are regulated by tyrosine phosphorylation and mediated by the opposing actions of protein tyrosine kinases and phosphatases. Protein tyrosine phosphatases are emerging as drug targets, but poor cell permeability of inhibitors has limited the development of drugs targeting these enzymes [Tautz L, et al. (2006) Expert Opin Ther Targets 10:157–177]. Here we developed a method to monitor tyrosine phosphatase activity at the single-cell level and applied it to the identification of cell-permeable inhibitors. The method takes advantage of the fluorogenic properties of phosphorylated coumaryl amino propionic acid (pCAP), an analog of phosphotyrosine, which can be incorporated into peptides. Once delivered into cells, pCAP peptides were dephosphorylated by protein tyrosine phosphatases, and the resulting cell fluorescence could be monitored by flow cytometry and high-content imaging. The robustness and sensitivity of the assay was validated using peptides preferentially dephosphorylated by CD45 and T-cell tyrosine phosphatase and available inhibitors of these two enzymes. The assay was applied to high-throughput screening for inhibitors of CD45, an important target for autoimmunity and infectious diseases [Hermiston ML, et al. (2003) Annu Rev Immunol 21:107–137]. We identified four CD45 inhibitors that showed activity in T cells and macrophages. These results indicate that our assay can be applied to primary screening for inhibitors of CD45 and of other protein tyrosine phosphatases to increase the yield of biologically active inhibitors

The colour-magnitude relation of Elliptical and Lenticular galaxies in the ESO Distant Cluster Survey

We study the colour-magnitude relation (CMR) for a sample of 172 morphologically-classified E/S0 cluster galaxies from the ESO Distant Cluster Survey (EDisCS) at 0.4<z<0.8. The intrinsic colour scatter about the CMR is very small (0.076) in rest-frame U-V. Only 7% of the galaxies are significantly bluer than the CMR. The scarcity of blue S0s indicates that, if they are the descendants of spirals, these were already red when they became S0s. We observe no dependence of the CMR scatter with redshift or cluster velocity dispersion. This implies that by the time cluster E/S0s achieve their morphology, the vast majority have already joined the red sequence. We estimate the galaxy formation redshift z_F for each cluster and find that it does not depend on the cluster velocity dispersion. However, z_F increases weakly with cluster redshift. This trend becomes clearer when including higher-z clusters from the literature, suggesting that, at any given z, in order to have a population of fully-formed E and S0s they needed to have formed most of their stars 2-4 Gyr prior to observation. In other words, the galaxies that already have early-type (ET) morphologies also have reasonably-old stellar populations. This is partly a manifestation of the "progenitor bias", but also a consequence of the fact that the vast majority of the ETs in clusters (in particular the massive ones) were already red by the time they achieved their morphology. E and S0 galaxies exhibit very similar colour scatter, implying similar stellar population ages. We also find that fainter ETs finished forming their stars later, consistent with the cluster red sequence being built over time and the brightest galaxies reaching the red sequence earlier than fainter ones. Finally, we find that the ET cluster galaxies must have had their star formation truncated over an extended period of at least 1 Gyr. [abridged]Comment: 14 pages, 12 figures, accepted for publication in MNRA

A Happy Abundance : Tales, Memoirs and More Past and Present in Wayne, Maine

https://digitalmaine.com/wayne_books/1002/thumbnail.jp

Antibody mediated targeting of the FGFR1c isoform increases glucose uptake in white and brown adipose tissue in male mice

The increased prevalence of obesity and its cardiometabolic implications demonstrates the imperative to identify novel therapeutic targets able to effect meaningful metabolic changes in this population. Antibody-mediated targeting of fibroblast growth factor receptor 1c isoform (FGFR1c) has been shown to ameliorate hyperglycaemia and protect from diet- and genetically-induced obesity in rodents and non-human primates. However, it is currently unknown which tissue(s) contribute to this glucose lowering effect. Thus, to elucidate this effect we treated euglycaemic mice with H7, a monoclonal antibody which selectively targets the FGFR1c isoform, and employed whole body positron emission computed tomography with a glucose tracer (18F-flurodeoxyglucose). Treatment with H7 increased basal glucose uptake in white and brown adipose tissues (WAT and BAT respectively), the brain and liver, but reduced it in the quadricep muscles. Consequentially, blood glucose was significantly reduced in response to treatment. Under insulin-stimulated conditions, the effects of H7 were maintained in WAT, BAT, liver and muscle. Treatment with H7 decreased triglyceride content and increased adipose triglyceride lipase content in white adipose tissue, whilst increasing activation of acetyl coenzyme A carboxylase, suggesting futile cycling of triglycerides, albeit favouring net hydrolysis. We demonstrated, in vitro, this is a direct effect of treatment in adipose tissue as basal cellular respiration and glucose uptake were increased in response to treatment. Taken together, these data suggest that antibody-mediated targeting of FGFR1c exerts its powerful glucose-lowering efficacy primarily due to increased glucose uptake in adipose tissue

Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease

Two Novel Susceptibility Loci for Prostate Cancer in Men of African Ancestry

Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, and genetic influences. To investigate the genetic basis of prostate cancer in men of African ancestry, we performed a genome-wide association meta-analysis using two-sided statistical tests in 10 202 case subjects and 10 810 control subjects. We identified novel signals on chromosomes 13q34 and 22q12, with the risk-associated alleles found only in men of African ancestry (13q34: rs75823044, risk allele frequency = 2.2%, odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.37 to 1.76, P = 6.10 × 10−12; 22q12.1: rs78554043, risk allele frequency = 1.5%, OR = 1.62, 95% CI = 1.39 to 1.89, P = 7.50 × 10−10). At 13q34, the signal is located 5’ of the gene IRS2 and 3’ of a long noncoding RNA, while at 22q12 the candidate functional allele is a missense variant in the CHEK2 gene. These findings provide further support for the role of ancestry-specific germline variation in contributing to population differences in prostate cancer risk