Integrating archaeology and ancient DNA analysis to address invasive species colonization in the Gulf of Alaska

The intentional and unintentional movement of plants and animals by humans has transformed ecosystems and landscapes globally. Assessing when and how a species was introduced are central to managing these transformed landscapes, particularly in island environments. In the Gulf of Alaska, there is considerable interest in the history of mammal introductions and rehabilitating Gulf of Alaska island environments by eradicating mammals classified as invasive species. The Arctic ground squirrel (Urocitellus parryii) is of concern because it affects vegetation and seabirds on Gulf of Alaska islands. This animal is assumed to have been introduced by historic settlers; however, ground squirrel remains in the prehistoric archaeological record of Chirikof Island, Alaska, challenge this timeline and suggest they colonized the islands long ago. We used 3 lines of evidence to address this problem: direct radiocarbon dating of archaeological squirrel remains; evidence of prehistoric human use of squirrels; and ancient DNA analysis of dated squirrel remains. Chirikof squirrels dated to at least 2000 years ago, and cut marks on squirrel bones suggested prehistoric use by people. Ancient squirrels also shared a mitochondrial haplotype with modern Chirikof squirrels. These results suggest that squirrels have been on Chirikof longer than previously assumed and that the current population of squirrels is closely related to the ancient population. Thus, it appears ground squirrels are not a recent, human‐mediated introduction and may have colonized the island via a natural dispersal event or an ancient human translocation.We thank T. Rick, D. Grayson, R. Fleischer, M. Hawkins, A. West, and C. Mikeska for their contributions to this research. We also thank 3 reviewers and the editors of Conservation Biology who greatly improved this paper. This work was funded by the National Geographic Society, the University of Maine, the Smithsonian Institution, and Boston University. The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the U.S. Fish and Wildlife Service. (National Geographic Society; University of Maine; Smithsonian Institution; Boston University)Published versio

Using Cartesian Coordinate Systems to Create, Classify, and Retrieve Biomedical Time-Series: Applications to 24-hour Ambulatory Blood Pressure Monitoring

Background: Ambulatory Blood Pressure Measurement (ABPM) allows physicians to monitor blood pressure variability under everyday living conditions and predicts clinical outcomes better than conventional blood-pressure measurement. ABPM can demonstrate mean arterial pressure (MAP) behavior over 24 hours relevant to clinical practice, such as nocturnal hypertension or increased blood pressure variability. We hypothesized that individuals with the same cardiovascular health status would have the same MAP signal (MAPs) waveform. Methods: This study reutilizes a data subset from the IDACO Consortium to create 24-hour MAPs. We assigned all the MAPs to data matrix X, performed principal components analysis (PCA) to X, and calculated the percentage of the total variance explained by each of the 82 principal components (PC). The first three PC explained 85.03%, 9.47%, and 5.50% of the total variance. We used every MAP signal\u27s first three PC scores as their three-dimensional Euclidean Space (x, y, z) coordinates and assigned them to matrix C. Then, we calculated hierarchical clusters of the rows of C with Ward\u27s linkage minimum variance algorithm and a Euclidian metric and encoded this information on the agglomerative hierarchical cluster tree Z. We determined the gap statistic in Z to obtain the optimal number of clusters. We created seven agglomerative clusters from the linkages stored in Z, using Ward’s distance as the criterion for defining the clusters. Finally, we plotted and colored the mapped MAPs by their assigned cluster number at the locations specified by their (x, y, z) coordinates. Results: The MAPs cartesian representations show that MAPs with similar waveforms cluster in the same three-dimensional Euclidean subspace. These patterns identified individuals with dipping and non-dipping blood pressure behavior, which is relevant to clinical management. Conclusions: Mapping a set of physiological signals into a Euclidian space creates a mathematical formalism that provides a statistical framework to classify physiological signals by their waveform. By applying our method to existing electrophysiological and physiological databases, we can cluster any biomedical time-series (blood pressure, ECG, EEG, EMG, patch-clamp, single-unit recordings, etc.) by physiologic or pathological waveform, so further epidemiological and genetic studies can be conducted on the subjects or tissue samples sharing similar patterns

A small molecule ApoE4-targeted therapeutic candidate that normalizes sirtuin 1 levels and improves cognition in an Alzheimer's disease mouse model.

We describe here the results from the testing of a small molecule first-in-class apolipoprotein E4 (ApoE4)-targeted sirtuin1 (SirT1) enhancer, A03, that increases the levels of the neuroprotective enzyme SirT1 while not affecting levels of neurotoxic sirtuin 2 (SirT2) in vitro in ApoE4-transfected cells. A03 was identified by high-throughput screening (HTS) and found to be orally bioavailable and brain penetrant. In vivo, A03 treatment increased SirT1 levels in the hippocampus of 5XFAD-ApoE4 (E4FAD) Alzheimer's disease (AD) model mice and elicited cognitive improvement while inducing no observed toxicity. We were able to resolve the enantiomers of A03 and show using in vitro models that the L-enantiomer was more potent than the corresponding D-enantiomer in increasing SirT1 levels. ApoE4 expression has been shown to decrease the level of the NAD-dependent deacetylase and major longevity determinant SirT1 in brain tissue and serum of AD patients as compared to normal controls. A deficiency in SirT1 level has been recently implicated in increased tau acetylation, a dominant post-translational modification and key pathological event in AD and tauopathies. Therefore, as a novel approach to therapeutic development for AD, we targeted identification of compounds that enhance and normalize brain SirT1 levels

The Benefits of Using XML Technologies in Astronomical Data Retrieval and Interpretation

This paper describes a solution found during recent research that could provide improvements in the efficiency, reliability and cost of retrieving stored astronomical data. This solution uses XML Technologies in showing that when querying a variety of astronomical data sources a standardised data structure can be output into an XML query results Document. This paper shows the astronomical XMLSchema that has been partially developed in conjunction with simple custom supporting system software. It also discusses briefly possible future implications

To What Extent do Fiscal Regimes Equalize Opportunities for Income Acquisition Among Citizens?

This project employs the theory of equality of opportunity, described in Roemer's book (Equality of Opportunity, Harvard University Press, 1998), to compute the extent to which tax-and-transfer regimes in ten countries equalize opportunities among citizens for income acquisition. Roughly speaking, equality of opportunity for incomes has been achieved in a country when it is the case that the distributions of post-fisc income are the same for different types of citizen, where a citizen's type is defined by the socioeconomic status of his parents. Intuitively, a country will have equalized opportunity if the chances of earning high (or low) income are equal for citizens from all family backgrounds. Of course, pre-fisc income distributions, by type, will not be identical, as long as the educational system does not entirely make up for the disadvantage that children, who come from poor families face, but the tax-and-transfer system can play a role in rectifying that inequality. We include, in our computation, two numbers that summarize the extent to which each country's current fiscal regime achieves equalization of opportunities for income, and the deadweight loss that would be incurred by moving to the regime that does.

Energy Evaluation of Pumping Systems in a Clean Water Plant: A Study Case

This paper presents a methodology based on the ISO-50001 standard to assess the energy impact of replacing standard efficiency motors with high-efficiency motors driven by variable speed drives in an industrial pumping system. The methodology includes the inspection and installation of the new technology, measurements, and data processing, as well as the analysis of the results. In addition, an energy efficiency indicator, an energy baseline, and a Pareto diagram are used, while the harmonics generated by new technologies are evaluated. The contribution of the methodology is that it allows for a comprehensive energy diagnosis using easily measurable data like electricity consumption and water flow, replacing the measurement of the motor\u27s mechanical power in industrial conditions, which is a current challenge. The methodology applied in the case study showed that the technological changes made saved 36% of energy, and that the variable speed drives increased current harmonics by 10%

The electrochemistry of 5-halocytosines at carbon based electrodes towards epigenetic sensing

Epigenetic modifications in DNA are strongly linked to the triggering and development of pathophysiological disorders and cancer diseases. The halogenation of DNA via radical species, particularly the formation of 5-chlorocytosine (ClC), has recently emerged as epigenetic modification. This work deals for the first time with the exploration of the electrochemical behaviour of ClC on different carbon electrodes such as glassy carbon and boron-doped diamond using cyclic voltammetry and square wave voltammetry. When comparing both carbon materials, the use of glassy carbon turned out to be the appropriate in terms of a more well-defined anodic wave and higher sensitivity. The electrochemical oxidation potential of ClC resulted to be linearly dependent on the pH with a maximum current intensity in acetic acid buffer solution under the conditions used. Moreover, a linear response between peak current intensity and ClC concentration was obtained within the range of 200 and 1000 μM with a limit of detection of 200 μM. In order to elucidate the reaction mechanism of the process, the main oxidation products after a preparative electrolysis were detected by HPLC-MS. Simultaneous detection of ClC in the presence of the unmodified cytosine and mixtures containing other nucleic bases such as guanine, adenine and thymine was also addressed. Finally, the effect of the halogen atom (X = F, Cl, Br) located at position C-5 of the cytosine entity upon the electrooxidation process was examined by theoretical calculations, too.I.S.M., N.H.I. and J.I. thank the Ministerio de Economia y Competitividad MINECO, Spain for its financial support by the research projects CTQ2013-48280-C3-3-R and CTQ2016-76231-C2-2-R

A comparison of RNA amplification techniques at sub-nanogram input concentration

<p>Abstract</p> <p>Background</p> <p>Gene expression profiling of small numbers of cells requires high-fidelity amplification of sub-nanogram amounts of RNA. Several methods for RNA amplification are available; however, there has been little consideration of the accuracy of these methods when working with very low-input quantities of RNA as is often required with rare clinical samples. Starting with 250 picograms-3.3 nanograms of total RNA, we compared two linear amplification methods 1) modified T7 and 2) Arcturus RiboAmp HS and a logarithmic amplification, 3) Balanced PCR. Microarray data from each amplification method were validated against quantitative real-time PCR (QPCR) for 37 genes.</p> <p>Results</p> <p>For high intensity spots, mean Pearson correlations were quite acceptable for both total RNA and low-input quantities amplified with each of the 3 methods. Microarray filtering and data processing has an important effect on the correlation coefficient results generated by each method. Arrays derived from total RNA had higher Pearson's correlations than did arrays derived from amplified RNA when considering the entire unprocessed dataset, however, when considering a gene set of high signal intensity, the amplified arrays had superior correlation coefficients than did the total RNA arrays.</p> <p>Conclusion</p> <p>Gene expression arrays can be obtained with sub-nanogram input of total RNA. High intensity spots showed better correlation on array-array analysis than did unfiltered data, however, QPCR validated the accuracy of gene expression array profiling from low-input quantities of RNA with all 3 amplification techniques. RNA amplification and expression analysis at the sub-nanogram input level is both feasible and accurate if data processing is used to focus attention to high intensity genes for microarrays or if QPCR is used as a gold standard for validation.</p

Isolated Diastolic Hypertension in the IDACO Study: An Age-Stratified Analysis Using 24-Hour Ambulatory Blood Pressure Measurements

The prognostic implications of isolated diastolic hypertension (IDH), as defined by 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines, have not been tested using ambulatory blood pressure (BP) monitor thresholds (ie, 24-hour mean systolic BP \u3c125 mm Hg and diastolic BP ≥75 mm Hg). We analyzed data from 11 135 participants in the IDACO (International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes). Using 24-hour mean ambulatory BP monitor values, we performed Cox regression testing independent associations of IDH with death or cardiovascular events. Analyses were conducted in the cohort overall, as well as after age stratification (\u3c50 years versus ≥50 years). The median age at baseline was 54.7 years and 49% were female. Over a median follow-up of 13.8 years, 2836 participants died, and 2049 experienced a cardiovascular event. Overall, irrespective of age, IDH on 24-hour ambulatory BP monitor defined by 2017 American College of Cardiology/American Heart Association criteria was not significantly associated with death (hazard ratio, 0.95 [95% CI, 0.79–1.13]) or cardiovascular events (hazard ratio, 1.14 [95% CI, 0.94–1.40]), compared with normotension. However, among the subgroup \u3c50 years old, IDH was associated with excess risk for cardiovascular events (2.87 [95% CI, 1.72–4.80]), with evidence for effect modification based on age (P interaction \u3c0.001). In conclusion, using ambulatory BP monitor data, this study suggests that IDH defined by 2017 American College of Cardiology/American Heart Association criteria is not a risk factor for cardiovascular disease in adults aged 50 years or older but is a risk factor among younger adults. Thus, age is an important consideration in the clinical management of adults with IDH