704 research outputs found

    Winter Movements of Louisiana Pine Snakes (Pituophis ruthveni) in Texas and Louisiana

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    Despite concerns that the Louisiana Pine Snake (Pituophis ruthveni) has been extirpated from large portions of its historic range, only a limited number of studies on their movement patterns have been published. Winter movement patterns are of particular interest since it has been hypothesized that impacts of management practices would be reduced during the winter. Using radiotelemetry, we determined winter movement patterns of Louisiana Pine Snakes (11 males, 8 females) in 5 study areas (2 in Louisiana and 3 in Texas). Movements during winter (November–February) were greatly curtailed compared to the remainder of the year; however, snakes occasionally undertook substantial movements. Relocations were typically within the snake’s previous active-season home range, and movements were more frequent in the early portion of winter. All hibernation sites were within Baird’s Pocket Gopher (Geomys breviceps) burrow systems at depths ranging from 13–25 cm. Louisiana Pine Snakes did not use communal hibernacula, nor did individual snakes return to previously used sites in successive years

    Changes in Îł-secretase activity and specificity caused by the introduction of consensus aspartyl protease active motif in Presenilin 1

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    Presenilin (PS1 or PS2) is an essential component of the active γ-secretase complex that liberates the Aβ peptides from amyloid precursor protein (APP). PS1 is regarded as an atypical aspartyl protease harboring two essential aspartic acids in the context of the sequence D257LV and D385FI, respectively, rather than the typical DTG...DTG catalytic motif of classical aspartyl proteases. In the present studies, we introduced the sequence DTG in PS1 at and around the catalytic D257 and D385 residues to generate three PS1 mutants: D257TG, D385TG, and the double-mutant D257TG/D385TG. The effects of these changes on the γ-secretase activity in the presence or absence of γ-secretase inhibitors and modulators were investigated. The results showed that PS1 mutants having D385TG robustly enhanced Aβ42 production compared to the wild type (wt), and were more sensitive than wt to inhibition by a classical aspartyl protease transition state mimic, and fenchylamine, a sulfonamide derivative. Unlike wt PS1 and some of its clinical mutants, all three PS1 artificial mutants decreased cleavage of Notch S3-site, suggesting that these artificial mutations may trigger conformational changes at the substrate docking and catalytic site that cause alteration of substrate specificity and inhibition pattern. Consistent with this notion, we have found that NSAID enzymatic inhibitors of COX, known modulators of the γ-secretase activity, cause PS1 mutants containing D385TG to produce higher levels of both Aβ38 and Aβ42, but to reduce levels of Aβ39, showing a pattern of Aβ formation different from that observed with wild type PS1 and its clinical mutants. This study provides an important structural clue for the rational design of drugs to inhibit processing of APP at the γ-site without interfering with Notch processing

    Osteomacs interact with megakaryocytes and osteoblasts to regulate murine hematopoietic stem cell function

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    Networking between hematopoietic stem cells (HSCs) and cells of the hematopoietic niche is critical for stem cell function and maintenance of the stem cell pool. We characterized calvariae-resident osteomacs (OMs) and their interaction with megakaryocytes to sustain HSC function and identified distinguishing properties between OMs and bone marrow (BM)–derived macrophages. OMs, identified as CD45+F4/80+ cells, were easily detectable (3%-5%) in neonatal calvarial cells. Coculture of neonatal calvarial cells with megakaryocytes for 7 days increased OM three- to sixfold, demonstrating that megakaryocytes regulate OM proliferation. OMs were required for the hematopoiesis-enhancing activity of osteoblasts, and this activity was augmented by megakaryocytes. Serial transplantation demonstrated that HSC repopulating potential was best maintained by in vitro cultures containing osteoblasts, OMs, and megakaryocytes. With or without megakaryocytes, BM-derived macrophages were unable to functionally substitute for neonatal calvarial cell–associated OMs. In addition, OMs differentiated into multinucleated, tartrate resistant acid phosphatase–positive osteoclasts capable of bone resorption. Nine-color flow cytometric analysis revealed that although BM-derived macrophages and OMs share many cell surface phenotypic similarities (CD45, F4/80, CD68, CD11b, Mac2, and Gr-1), only a subgroup of OMs coexpressed M-CSFR and CD166, thus providing a unique profile for OMs. CD169 was expressed by both OMs and BM-derived macrophages and therefore was not a distinguishing marker between these 2 cell types. These results demonstrate that OMs support HSC function and illustrate that megakaryocytes significantly augment the synergistic activity of osteoblasts and OMs. Furthermore, this report establishes for the first time that the crosstalk between OMs, osteoblasts, and megakaryocytes is a novel network supporting HSC function

    Ethnic variation in validity of the estimated obesity prevalence using self-reported weight and height measurements

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    <p>Abstract</p> <p>Background</p> <p>We examined ethnic differences between levels of body mass index (BMI) based on self-reported and measured body height and weight and the validity of self-reports used to estimate the prevalence of obesity (BMI≥30 kg/m<sup>2</sup>) in Turkish, Moroccan, and Dutch people in the Netherlands. Furthermore, we investigated whether BMI levels and the prevalence of obesity in Turkish and Moroccan people with incomplete self-reports (missing height or weight) differ from those with complete self-reports.</p> <p>Methods</p> <p>Data on self-reported and measured height and weight were collected in a population-based survey among 441 Dutch, 414 Turks and 344 Moroccans aged 18 to 69 years in Amsterdam, the Netherlands in 2004. BMI and obesity were calculated from self-reported and measured height and weight.</p> <p>Results</p> <p>The difference between measured and estimated BMI was larger in Turkish and Moroccan women than in Dutch women, which was explained by the higher BMI of the Turkish and Moroccan women. In men we found no ethnic differences between measured and estimated BMI. Sensitivity to detect obesity was low and specificity was high. In participants with available self-reported and measured height and weight, self-reports produced a similar underestimation of the obesity prevalence in all ethnic groups. However, many obese Turkish and Moroccan women had incomplete self-reports, missing height or weight, resulting in an additional underestimation of the prevalence of obesity. Among men (all ethnicities) and Dutch women, the availability of height or weight by self-report did not differ between obese and non obese participants.</p> <p>Conclusions</p> <p>BMI based on self-reports is underestimated more by Turkish and Moroccan women than Dutch women, which is explained by the higher BMI of Turkish and Moroccan women. Further, in women, ethnic differences in the estimation of obesity prevalence based on self-reports do exist and are due to incomplete self-reports in obese Turkish and Moroccan women. In men, ethnicity is not associated with discrepancies between levels of BMI and obesity prevalence based on measurements and self-reports. Hence, our results indicate that using measurements to accurately determine levels of BMI and obesity prevalence in public health research seems even more important in Turkish and Moroccan migrant women than in other populations.</p

    Why nature matters: A systematic review of intrinsic, instrumental, and relational values

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    \ua9 2023 The Author(s). Published by Oxford University Press on behalf of the American Institute of Biological Sciences. In this article, we present results from a literature review of intrinsic, instrumental, and relational values of nature conducted for the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services, as part of the Methodological Assessment of the Diverse Values and Valuations of Nature. We identify the most frequently recurring meanings in the heterogeneous use of different value types and their association with worldviews and other key concepts. From frequent uses, we determine a core meaning for each value type, which is sufficiently inclusive to serve as an umbrella over different understandings in the literature and specific enough to help highlight its difference from the other types of values. Finally, we discuss convergences, overlapping areas, and fuzzy boundaries between different value types to facilitate dialogue, reduce misunderstandings, and improve the methods for valuation of nature\u27s contributions to people, including ecosystem services, to inform policy and direct future research

    Integrating Machine Learning for Planetary Science: Perspectives for the Next Decade

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    Machine learning (ML) methods can expand our ability to construct, and draw insight from large datasets. Despite the increasing volume of planetary observations, our field has seen few applications of ML in comparison to other sciences. To support these methods, we propose ten recommendations for bolstering a data-rich future in planetary science.Comment: 10 pages (expanded citations compared to 8 page submitted version for decadal survey), 3 figures, white paper submitted to the Planetary Science and Astrobiology Decadal Survey 2023-203

    Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.

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    Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 Ă— 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma

    Asthma-susceptibility variants identified using probands in case-control and family-based analyses

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    <p>Abstract</p> <p>Background</p> <p>Asthma is a chronic respiratory disease whose genetic basis has been explored for over two decades, most recently via genome-wide association studies. We sought to find asthma-susceptibility variants by using probands from a single population in both family-based and case-control association designs.</p> <p>Methods</p> <p>We used probands from the Childhood Asthma Management Program (CAMP) in two primary genome-wide association study designs: (1) probands were combined with publicly available population controls in a case-control design, and (2) probands and their parents were used in a family-based design. We followed a two-stage replication process utilizing three independent populations to validate our primary findings.</p> <p>Results</p> <p>We found that single nucleotide polymorphisms with similar case-control and family-based association results were more likely to replicate in the independent populations, than those with the smallest p-values in either the case-control or family-based design alone. The single nucleotide polymorphism that showed the strongest evidence for association to asthma was rs17572584, which replicated in 2/3 independent populations with an overall p-value among replication populations of 3.5E-05. This variant is near a gene that encodes an enzyme that has been implicated to act coordinately with modulators of Th2 cell differentiation and is expressed in human lung.</p> <p>Conclusions</p> <p>Our results suggest that using probands from family-based studies in case-control designs, and combining results of both family-based and case-control approaches, may be a way to augment our ability to find SNPs associated with asthma and other complex diseases.</p

    Comprehensive genetic assessment of a functional TLR9 promoter polymorphism: no replicable association with asthma or asthma-related phenotypes

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    <p>Abstract</p> <p>Background</p> <p>Prior studies suggest a role for a variant (rs5743836) in the promoter of toll-like receptor 9 (TLR9) in asthma and other inflammatory diseases. We performed detailed genetic association studies of the functional variant rs5743836 with asthma susceptibility and asthma-related phenotypes in three independent cohorts.</p> <p>Methods</p> <p>rs5743836 was genotyped in two family-based cohorts of children with asthma and a case-control study of adult asthmatics. Association analyses were performed using chi square, family-based and population-based testing. A luciferase assay was performed to investigate whether rs5743836 genotype influences TLR9 promoter activity.</p> <p>Results</p> <p>Contrary to prior reports, rs5743836 was not associated with asthma in any of the three cohorts. Marginally significant associations were found with FEV<sub>1 </sub>and FVC (p = 0.003 and p = 0.008, respectively) in one of the family-based cohorts, but these associations were not significant after correcting for multiple comparisons. Higher promoter activity of the CC genotype was demonstrated by luciferase assay, confirming the functional importance of this variant.</p> <p>Conclusion</p> <p>Although rs5743836 confers regulatory effects on TLR9 transcription, this variant does not appear to be an important asthma-susceptibility locus.</p

    Development and quantitative analyses of a universal rRNA-subtraction protocol for microbial metatranscriptomics

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    Metatranscriptomes generated by pyrosequencing hold significant potential for describing functional processes in complex microbial communities. Meeting this potential requires protocols that maximize mRNA recovery by reducing the relative abundance of ribosomal RNA, as well as systematic comparisons to identify methodological artifacts and test for reproducibility across data sets. Here, we implement a protocol for subtractive hybridization of bacterial rRNA (16S and 23S) that uses sample-specific probes and is applicable across diverse environmental samples. To test this method, rRNA-subtracted and unsubtracted transcriptomes were sequenced (454 FLX technology) from bacterioplankton communities at two depths in the oligotrophic open ocean, yielding 10 data sets representing ~350 Mbp. Subtractive hybridization reduced bacterial rRNA transcript abundance by 40–58%, increasing recovery of non-rRNA sequences up to fourfold (from 12% to 20% of total sequences to 40–49%). In testing this method, we established criteria for detecting sequences replicated artificially via pyrosequencing errors and identified such replicates as a significant component (6–39%) of total pyrosequencing reads. Following replicate removal, statistical comparisons of reference genes (identified via BLASTX to NCBI-nr) between technical replicates and between rRNA-subtracted and unsubtracted samples showed low levels of differential transcript abundance (<0.2% of reference genes). However, gene overlap between data sets was remarkably low, with no two data sets (including duplicate runs from the same pyrosequencing library template) sharing greater than 17% of unique reference genes. These results indicate that pyrosequencing captures a small subset of total mRNA diversity and underscores the importance of reliable rRNA subtraction procedures to enhance sequencing coverage across the functional transcript pool.Agouron InstituteGordon and Betty Moore FoundationUnited States. Dept. of Energy. Office of ScienceNational Science Foundation (U.S.) (NSF Science and Technology Center Award EF0424599
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