Body Fluid Identification in Samples Collected after Intimate and Social Contact: A Comparison of Two mRNA Profiling Methods and the Additional Information Gained by cSNP Genotypes

The ability to associate a contributor with a specific body fluid in a crime stain can aid casework investigation. The detection of body fluids combined with DNA analyses may supply essential information, but as the two tests are independent, they may not be associated. Recently, the analysis of coding region SNPs (cSNPs) within the RNA transcript has been proven to be a promising method to face this challenge. In this study, we performed targeted RNA sequencing of 158 samples (boxershorts, fingernail swabs and penile swabs) collected from 12 couples at different time points post-intimate contact and after non-intimate contact, using the Ion S5™ System and BFID-cSNP-6F assay. The aim of the study was to compare the performance of the MPS and CE methods in the detection of mRNA markers, and to associate body fluids with contributors by their cSNP genotypes. The results of the study show a lower success rate in the detection of vaginal mucosa by the MPS compared to the CE method. However, the additional information obtained with the cSNP genotypes could successfully associate body fluids with contributors in most cases

Intestinal APCs of the endogenous nanomineral pathway fail to express PD-L1 in Crohn's disease.

Crohn's disease is a chronic inflammatory condition most commonly affecting the ileum and colon. The aetiology of Crohn's disease is complex and may include defects in peptidoglycan recognition, and/or failures in the establishment of intestinal tolerance. We have recently described a novel constitutive endogenous delivery system for the translocation of nanomineral-antigen-peptidoglycan (NAP) conjugates to antigen presenting cells (APCs) in intestinal lymphoid patches. In mice NAP conjugate delivery to APCs results in high surface expression of the immuno-modulatory molecule programmed death receptor ligand 1 (PD-L1). Here we report that NAP conjugate positive APCs in human ileal tissues from individuals with ulcerative colitis and intestinal carcinomas, also have high expression of PD-L1. However, NAP-conjugate positive APCs in intestinal tissue from patients with Crohn's disease show selective failure in PD-L1 expression. Therefore, in Crohn's disease intestinal antigen taken up by lymphoid patch APCs will be presented without PD-L1 induced tolerogenic signalling, perhaps initiating disease

Síndrome da fragilidade entre idosos e fatores associados: comparação de dois municípios

Objetivo: comparar el síndrome de la fragilidad en el adulto mayor que viven en el domicilio en dos ciudades brasileiras e identificar los factores relacionados a las variables sociodemográficas y de salud. Método: estudio transversal de base poblacional por conglomerado, con 480 adultos mayores de las ciudades de Ribeirão Preto/SP y João Pessoa/PB, con aplicación de los instrumentos de Mini Examen del Estado Mental y las escalas de Fragilidad de Edmonton, Depresión Geriátrica y Lawton y Brody. Fueron utilizados el análisis descriptivo, Test Chi-cuadrado, Test de Fisher, Test t Student, Correlación de Spermann y Regresión Logística. En todos los análisis, se adoptó el nivel de significancia de p≤0,05. Resultados: en relación a la fragilidad, se verificó que vivir en Ribeirão Preto, presentar edad avanzada, baja escolaridad, múltiples enfermedades crónicas, disminución del estado cognitivo y capacidad funcional, además de los síntomas depresivos, son factores que se asocian con el síndrome de la fragilidad, en ambas ciudades. Conclusión: se identificó que el síndrome de la fragilidad en los adultos mayores de ambas ciudades tienen relación con el local donde el adulto mayor vive, con la edad, la escolaridad, el número de enfermedades, la disminución del estado cognitivo, de la capacidad funcional y presencia de síntomas depresivos.Objetivo: comparar a síndrome da fragilidade entre idosos que vivem no domicílio em dois municípios brasileiros e identificar fatores relacionados às variáveis sociodemográficas e de saúde. Método: estudo transversal de base populacional por conglomerado, com 480 idosos dos municípios de Ribeirão Preto/SP e João Pessoa/PB, com aplicação dos instrumentos do Mini Exame do Estado Mental e as escalas de Fragilidade de Edmonton, Depressão Geriátrica e Lawton e Brody. Foram utilizados a análise descritiva, Teste Qui Quadrado, Teste de Fisher, Teste t Student, Correlação de Spermann e Regressão Logística. Em todas as análises, adotou-se o nível de significância de p≤0,05. Resultados: em relação à fragilidade, verificou-se que morar em Ribeirão Preto, apresentar idade avançada, baixa escolaridade, múltiplas doenças crônicas, diminuição do estado cognitivo e capacidade funcional, além dos sintomas depressivos, são fatores que se associam com a síndrome da fragilidade, em ambas as cidades. Conclusão: identificou-se que a síndrome da fragilidade em idosos de ambos os municípios estudados tem relação com o local onde o idoso mora, com a idade, a escolaridade, o número de doenças, a diminuição do estado cognitivo, da capacidade funcional e presença de sintomas depressivos.Objective: to compare the frailty syndrome among elderly people living at home in two Brazilian cities and to identify factors related to sociodemographic and health-related variables. Method: population-based cross-sectional study with 480 elderly individuals from the cities of Ribeirão Preto/SP and João Pessoa/PB, with application of the Mini Mental State Examination instruments and the Edmonton Frailty, Geriatric Depression and Lawton and Brody scales. Descriptive analysis, Chi-square test, Fisher’s test, Student’s t-test, Spermann’s correlation and Logistic regression were used. In all analyzes, the level of significance was set at p≤0.05. Results: in relation to frailty, it was verified that living in Ribeirão Preto, presenting advanced age, low schooling, multiple chronic diseases, reduced cognitive status and functional capacity, besides depressive symptoms, are factors associated with the frailty syndrome, in both cities. Conclusion: we identified that the frailty syndrome in the elderly of both cities has a relation with the place where the elderly person lives, age, schooling, number of diseases, reduction of cognitive status, functional capacity and presence of symptoms depressive

The Mid-Infrared Environments of High-Redshift Radio Galaxies

Taking advantage of the impressive sensitivity of Spitzer to detect massive galaxies at high redshift, we study the mid-infrared environments of powerful, high-redshift radio galaxies at 1.2<z<3. Galaxy cluster member candidates were isolated using a single Spitzer/IRAC mid-infrared color criterion, [3.6]-[4.5]>-0.1 (AB), in the fields of 48 radio galaxies at 1.2<z<3. This simple IRAC color selection is effective at identifying galaxies at z>1.2. Using a counts-in-cell analysis, we identify a field as overdense when 15 or more red IRAC sources are found within 1arcmin (i.e.,~0.5Mpc at 1.2<z<3) of the radio galaxy to the 5sigma flux density limits of our IRAC data (f3.6=11.0uJy, f4.5=13.4uJy). We find that radio galaxies lie preferentially in medium to dense regions, with 73% of the targeted fields denser than average. Our (shallow) 120s data permit the rediscovery of previously known clusters and protoclusters associated with radio galaxies as well as the discovery of new promising galaxy cluster candidates at z>1.2.Comment: 14 pages, 7 figures, 3 tables, accepted for publication in Ap

Natural soda lakes provide compatible conditions for RNA and membrane function that could have enabled the origin of life

The origin of life likely occurred within environments that concentrated cellular precursors and enabled their co-assembly into cells. Soda lakes (those dominated by Na+ ions and carbonate species) can concentrate precursors of RNA and membranes, such as phosphate, cyanide, and fatty acids. Subsequent assembly of RNA and membranes into cells is a long-standing problem because RNA function requires divalent cations, e.g. Mg2+, but Mg2+ disrupts fatty acid membranes. The low solubility of Mg-containing carbonates limits soda lakes to moderate Mg2+ concentrations (∼1 mM), so we investigated whether both RNAs and membranes function within these lakes. We collected water from Last Chance Lake and Goodenough Lake in Canada. Because we sampled after seasonal evaporation, the lake water contained ∼1 M Na+ and ∼1 mM Mg2+ near pH 10. In the laboratory, nonenzymatic, RNA-templated polymerization of 2-aminoimidazole-activated ribonucleotides occurred at comparable rates in lake water and standard laboratory conditions (50 mM MgCl2, pH 8). Additionally, we found that a ligase ribozyme that uses oligonucleotide substrates activated with 2-aminoimidazole was active in lake water after adjusting pH from ∼10 to 9. We also observed that decanoic acid and decanol assembled into vesicles in a dilute solution that resembled lake water after seasonal rains, and that those vesicles retained encapsulated solutes despite salt-induced flocculation when the external solution was replaced with dry-season lake water. By identifying compatible conditions for nonenzymatic and ribozyme-catalyzed RNA assembly, and for encapsulation by membranes, our results suggest that soda lakes could have enabled cellular life to emerge on Earth, and perhaps elsewhere

Synthetic mimetics of the endogenous gastrointestinal nanomineral: Silent constructs that trap macromolecules for intracellular delivery.

Amorphous magnesium-substituted calcium phosphate (AMCP) nanoparticles (75-150nm) form constitutively in large numbers in the mammalian gut. Collective evidence indicates that they trap and deliver luminal macromolecules to mucosal antigen presenting cells (APCs) and facilitate gut immune homeostasis. Here, we report on a synthetic mimetic of the endogenous AMCP and show that it has marked capacity to trap macromolecules during formation. Macromolecular capture into AMCP involved incorporation as shown by STEM tomography of the synthetic AMCP particle with 5nm ultra-fine iron (III) oxohydroxide. In vitro, organic cargo-loaded synthetic AMCP was taken up by APCs and tracked to lysosomal compartments. The AMCP itself did not regulate any gene, or modify any gene regulation by its cargo, based upon whole genome transcriptomic analyses. We conclude that synthetic AMCP can efficiently trap macromolecules and deliver them to APCs in a silent fashion, and may thus represent a new platform for antigen delivery

Reduction of T-Helper Cell Responses to Recall Antigen Mediated by Codelivery with Peptidoglycan via the Intestinal Nanomineral-Antigen Pathway.

Naturally occurring intestinal nanomineral particles constituently form in the mammalian gut and trap luminal protein and microbial components. These cargo loaded nanominerals are actively scavenged by M cells of intestinal immune follicles, such as Peyer's patches and are passed to antigen-presenting cells. Using peripheral blood mononuclear cell populations as an in vitro model of nanomineral uptake and antigen presentation, we show that monocytes avidly phagocytose nanomineral particles bearing antigen and peptidoglycan (PGN), and that the presence of PGN within particles downregulates their cell surface MHC class II and upregulates programmed death receptor ligand 1. Nanomineral delivery of antigen suppresses antigen-specific CD4+ T cell responses, an effect that is enhanced in the presence of PGN. Blocking the interleukin-10 receptor restores CD4+ T cell responses to antigen codelivered with PGN in nanomineral form. Using human intestinal specimens, we have shown that the in vivo nanomineral pathway operates in an interleukin-10 rich environment. Consequently, the delivery of a dual antigen-PGN cargo by endogenous nanomineral in vivo is likely to be important in the establishment of intestinal tolerance, while their synthetic mimetics present a potential delivery system for therapeutic applications targeting the modulation of Peyer's patch T cell responses

Validation of Kepler's Multiple Planet Candidates. III: Light Curve Analysis & Announcement of Hundreds of New Multi-planet Systems

The Kepler mission has discovered over 2500 exoplanet candidates in the first two years of spacecraft data, with approximately 40% of them in candidate multi-planet systems. The high rate of multiplicity combined with the low rate of identified false-positives indicates that the multiplanet systems contain very few false-positive signals due to other systems not gravitationally bound to the target star (Lissauer, J. J., et al., 2012, ApJ 750, 131). False positives in the multi- planet systems are identified and removed, leaving behind a residual population of candidate multi-planet transiting systems expected to have a false-positive rate less than 1%. We present a sample of 340 planetary systems that contain 851 planets that are validated to substantially better than the 99% confidence level; the vast majority of these have not been previously verified as planets. We expect ~2 unidentified false-positives making our sample of planet very reliable. We present fundamental planetary properties of our sample based on a comprehensive analysis of Kepler light curves and ground-based spectroscopy and high-resolution imaging. Since we do not require spectroscopy or high-resolution imaging for validation, some of our derived parameters for a planetary system may be systematically incorrect due to dilution from light due to additional stars in the photometric aperture. None the less, our result nearly doubles the number of verified exoplanets.Comment: 138 pages, 8 Figures, 5 Tables. Accepted for publications in the Astrophysical Journa

Kepler-68: Three Planets, One With a Density Between That of Earth and Ice Giants

NASA's Kepler Mission has revealed two transiting planets orbiting Kepler-68. Follow-up Doppler measurements have established the mass of the innermost planet and revealed a third jovian-mass planet orbiting beyond the two transiting planets. Kepler-68b, in a 5.4 day orbit has mass 8.3 +/- 2.3 Earth, radius 2.31 +/- 0.07 Earth radii, and a density of 3.32 +/- 0.92 (cgs), giving Kepler-68b a density intermediate between that of the ice giants and Earth. Kepler-68c is Earth-sized with a radius of 0.953 Earth and transits on a 9.6 day orbit; validation of Kepler-68c posed unique challenges. Kepler-68d has an orbital period of 580 +/- 15 days and minimum mass of Msin(i) = 0.947 Jupiter. Power spectra of the Kepler photometry at 1-minute cadence exhibit a rich and strong set of asteroseismic pulsation modes enabling detailed analysis of the stellar interior. Spectroscopy of the star coupled with asteroseismic modeling of the multiple pulsation modes yield precise measurements of stellar properties, notably Teff = 5793 +/- 74 K, M = 1.079 +/- 0.051 Msun, R = 1.243 +/- 0.019 Rsun, and density 0.7903 +/- 0.0054 (cgs), all measured with fractional uncertainties of only a few percent. Models of Kepler-68b suggest it is likely composed of rock and water, or has a H and He envelope to yield its density of about 3 (cgs).Comment: 32 pages, 13 figures, Accepted to Ap