An Empirically Derived Three-Dimensional Laplace Resonance in the Gliese 876 Planetary System

We report constraints on the three-dimensional orbital architecture for all four planets known to orbit the nearby M dwarf Gliese 876 based solely on Doppler measurements and demanding long-term orbital stability. Our dataset incorporates publicly available radial velocities taken with the ELODIE and CORALIE spectrographs, HARPS, and Keck HIRES as well as previously unpublished HIRES velocities. We first quantitatively assess the validity of the planets thought to orbit GJ 876 by computing the Bayes factors for a variety of different coplanar models using an importance sampling algorithm. We find that a four-planet model is preferred over a three-planet model. Next, we apply a Newtonian MCMC algorithm to perform a Bayesian analysis of the planet masses and orbits using an n-body model in three-dimensional space. Based on the radial velocities alone, we find that a 99% credible interval provides upper limits on the mutual inclinations for the three resonant planets ($\Phi_{cb}<6.20^\circ$ for the "c" and "b" pair and $\Phi_{be}<28.5^\circ$ for the "b" and "e" pair). Subsequent dynamical integrations of our posterior sample find that the GJ 876 planets must be roughly coplanar ($\Phi_{cb}<2.60^\circ$ and $\Phi_{be}<7.87^\circ$), suggesting the amount of planet-planet scattering in the system has been low. We investigate the distribution of the respective resonant arguments of each planet pair and find that at least one argument for each planet pair and the Laplace argument librate. The libration amplitudes in our three-dimensional orbital model supports the idea of the outer-three planets having undergone significant past disk migration.Comment: 19 pages, 11 figures, 8 tables. Accepted to MNRAS. Posterior samples available at https://github.com/benelson/GJ87

Dual destructive and protective roles of adaptive immunity in neurodegenerative disorders.

Inappropriate T cell responses in the central nervous system (CNS) affect the pathogenesis of a broad range of neuroinflammatory and neurodegenerative disorders that include, but are not limited to, multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer\u27s disease and Parkinson\u27s disease. On the one hand immune responses can exacerbate neurotoxic responses; while on the other hand, they can lead to neuroprotective outcomes. The temporal and spatial mechanisms by which these immune responses occur and are regulated in the setting of active disease have gained significant recent attention. Spatially, immune responses that affect neurodegeneration may occur within or outside the CNS. Migration of antigen-specific CD4+ T cells from the periphery to the CNS and consequent immune cell interactions with resident glial cells affect neuroinflammation and neuronal survival. The destructive or protective mechanisms of these interactions are linked to the relative numerical and functional dominance of effector or regulatory T cells. Temporally, immune responses at disease onset or during progression may exhibit a differential balance of immune responses in the periphery and within the CNS. Immune responses with predominate T cell subtypes may differentially manifest migratory, regulatory and effector functions when triggered by endogenous misfolded and aggregated proteins and cell-specific stimuli. The final result is altered glial and neuronal behaviors that influence the disease course. Thus, discovery of neurodestructive and neuroprotective immune mechanisms will permit potential new therapeutic pathways that affect neuronal survival and slow disease progression

Two Transiting Earth-size Planets Near Resonance Orbiting a Nearby Cool Star

Discoveries from the prime Kepler mission demonstrated that small planets (< 3 Earth-radii) are common outcomes of planet formation. While Kepler detected many such planets, all but a handful orbit faint, distant stars and are not amenable to precise follow up measurements. Here, we report the discovery of two small planets transiting K2-21, a bright (K = 9.4) M0 dwarf located 65$\pm$6 pc from Earth. We detected the transiting planets in photometry collected during Campaign 3 of NASA's K2 mission. Analysis of transit light curves reveals that the planets have small radii compared to their host star, 2.60 $\pm$ 0.14% and 3.15 $\pm$ 0.20%, respectively. We obtained follow up NIR spectroscopy of K2-21 to constrain host star properties, which imply planet sizes of 1.59 $\pm$ 0.43 Earth-radii and 1.92 $\pm$ 0.53 Earth-radii, respectively, straddling the boundary between high-density, rocky planets and low-density planets with thick gaseous envelopes. The planets have orbital periods of 9.32414 days and 15.50120 days, respectively, and have a period ratio of 1.6624, very near to the 5:3 mean motion resonance, which may be a record of the system's formation history. Transit timing variations (TTVs) due to gravitational interactions between the planets may be detectable using ground-based telescopes. Finally, this system offers a convenient laboratory for studying the bulk composition and atmospheric properties of small planets with low equilibrium temperatures.Comment: Updated to ApJ accepted version; photometry available alongside LaTeX source; 10 pages, 7 figure

Development of a New Polymerase Chain Reaction Assay for the Rapid Detection of the Oral Pathogenic Bacterium, Selenomonas Noxia

Background In recent studies, periodontal health has been linked to being overweight and/or obese. Among common oral bacteria, Selenomonas noxia has been implicated in converting periodontal health to disease, and Selenomonas species have also been found in gastric ulcers. The objective of this study was to develop and validate a quantitative polymerase chain reaction (qPCR) assay for the specific and rapid detection of S. noxia. Methods Two oligonucleotide primer pairs and one probe were designed and tested to determine optimal amplification signal with three strains of S. noxia. The PCR assay was tested against fourteen non-target organisms, including closely related oral Selenomonads, one phylogenetically closely related bacterium, and two commonly isolated oral bacteria. Results One of the primer sets was more sensitive at detecting the target organism and was selected for optimization and validation experiments. The designed primers and probe amplified the target organism with 100 % specificity. PCR inhibition was observed with an internal positive control, and inhibition was resolved by diluting the DNA extract. Conclusions The qPCR assay designed in this study can be used to specifically detect S. noxiain the clinical setting and in future research involving the enhanced detection of S. noxia. The assay can also be used in epidemiological studies for understanding the role of S. noxia in disease processes including, but not limited to, oral health and obesity of infectious origin

miR-365 (microRNA): Potnetial Biomarker in Oral Squamous Cell Carcinoma Exosomes and Extracellular Vesicles

Introduction: miR-365 is a non-coding microRNA that regulates transcription and has been demonstrated to promote oncogenesis and metastasis in some cancers, while suppressing these effects in others. Many microRNAs are produced and then exported extracellularly in exosomes, which are small extracellular vesicles ranging from 30 to 100 nm that are found in eukaryotic fluids and facilitate many cellular functions. Exosomes and extracellular vesicles are produced by many cell types, including oral cancer cells—although no study to date has evaluated miR-365 and oral cancer exosomes or extracellular vesicles. Based on this information, our research question was to evaluate whether oral cancers produce exosomes or extracellular vesicles containing miR-365. Materials and Methods: Two commercially available oral cancer cell lines (SCC25 and CAL27) and a normal oral keratinocyte (OKF4) were grown in serum-free media, supplemented with exosome-depleted fetal bovine serum. Extracellular vesicles and exosomes were then isolated using the Invitrogen total exosome RNA and protein isolation kit for processing using the hsa-miR-365a-5p microRNA qPCR assay kit. Results: RNA was successfully isolated from the exosome-depleted supernatant from each cell line—SCC9, SCC15, SCC25, and CAL27 (oral squamous cell carcinomas) and OKF4 (oral epithelial cell line). Relative concentrations of RNA were similar among each cell line, which were not significantly different, p = 0.233. RNA quality was established by A260:A280 absorbance using a NanoDrop, revealing purity ranging 1.73–1.86. Expression of miR-16 was used to confirm the presence of microRNA from the extracted exosomes and extracellular vesicles. The presence of miR-365 was then confirmed and normalized to miR-16 expression, which demonstrated an increased level of miR-365 in both CAL27 and SCC25. In addition, the normalized relative quantity (RQ) for miR-365 exhibited greater variation among SCC25 (1.382–4.363) than CAL27 cells (1.248–1.536). Conclusions: These results confirm that miR-365 is not only expressed in oral cancer cell lines, but also is subsequently exported into exosomes and extracellular vesicles derived from these cultures. These data may help to contextualize the potential for this microRNA to contribute to the phenotypes and behaviors of oral cancers that express this microRNA. Future research will begin to investigate these potential mechanisms and pathways and to determine if miR-365 may be useful as an oral cancer biomarker for salivary or liquid biopsies

Controls on boron incorporation in cultured tests of the planktic foraminifer Orbulina universa

Culture experiments with living planktic foraminifers reveal that the ratio of boron to calcium (B/Ca) in Orbulina universa increases from 56 to 92 μmol mol−1 when pH is raised from 7.61+/–0.02 to 8.67+/–0.03 (total scale). Across this pH range, the abundances of carbonate, bicarbonate, and borate ions also change (+530, −500, and +170 μmol kg−1, respectively). Thus specific carbonate system control(s) on B/Ca remain unclear, complicating interpretation of paleorecords. B/Ca in cultured O. universa also increases with salinity (55–72 μmol mol−1 from 29.9–35.4‰) and seawater boron concentration (62–899 μmol mol−1 from 4–40 ppm B), suggesting that these parameters may need to be taken into account for paleorecords spanning large salinity changes (~ 2‰) and for samples grown in seawater whose boron concentration ([B]SW) differs from modern by more than 0.25 ppm. While our results are consistent with the predominant incorporation of the charged borate species B(OH)4−into foraminiferal calcite, the behavior of the partition coefficient KD (defined as [B/Ca]calcite/[B(OH)4−/HCO3−]seawater) cannot be explained by borate incorporation alone, and suggests the involvement of other pH-sensitive ions such as CO3 2− For a given increase in seawater B(OH)4−, the corresponding increase in B/Ca is stronger when B(OH)4− is raised by increasing [B]SW than when it is raised by increasing pH. These results suggest that B incorporation controls should be reconsidered. Additional insight is gained from laser-ablation ICP-MS profiles, which reveal variable B/Ca distributions within individual shells

Cranberry Polyphenols in Esophageal Cancer Inhibition: New Insights

Esophageal adenocarcinoma (EAC) is a cancer characterized by rapidly rising incidence and poor survival, resulting in the need for new prevention and treatment options. We utilized two cranberry polyphenol extracts, one proanthocyanidin enriched (C-PAC) and a combination of anthocyanins, flavonoids, and glycosides (AFG) to assess inhibitory mechanisms utilizing premalignant Barrett’s esophagus (BE) and EAC derived cell lines. We employed reverse phase protein arrays (RPPA) and Western blots to examine cancer-associated pathways and specific signaling cascades modulated by C-PAC or AFG. Viability results show that C-PAC is more potent than AFG at inducing cell death in BE and EAC cell lines. Based on the RPPA results, C-PAC significantly modulated 37 and 69 proteins in JH-EsoAd1 (JHAD1) and OE19 EAC cells, respectively. AFG treatment significantly altered 49 proteins in both JHAD1 and OE19 cells. Bioinformatic analysis of RPPA results revealed many previously unidentified pathways as modulated by cranberry polyphenols including NOTCH signaling, immune response, and epithelial to mesenchymal transition. Collectively, these results provide new insight regarding mechanisms by which cranberry polyphenols exert cancer inhibitory effects targeting EAC, with implications for potential use of cranberry constituents as cancer preventive agents

An Unidentified Filarial Species and its Impact on Fitness in Wild Populations of the Black-Footed Ferret (\u3ci\u3eMustela nigripes\u3c/i\u3e)

Disease can threaten the restoration of endangered species directly by substantially decreasing host survival or indirectly via incremental decreases in survival and reproduction. During a biomedical survey of reintroduced populations of the highly endangered black-footed ferret from 2002 to 2005, microfilariae discovered in the blood were putatively identified as Dirofilaria immitis, and widespread screening was initiated using a commercially available antigen-based ELISA test. A subset of animals (n = 16) was screened for D. immitis using a highly sensitive PCR-based assay. Microfilariae were also molecularly and morphologically characterized. Of 198 animals at six reintroduction sites, 12% had positive results using the ELISA test. No antigen-positive animals which were screened via PCR (n = 11) had positive PCR results, and all antigen-positive animals (n=24) were asymptomatic. No significant differences were found in body mass of antigen-positive (male: 1223±82 g [mean±SD], female: 726±75 g) vs. antigen-negative (male: 1,198±119 g, female: 710±53 g) individuals (P=0.4). Antigen prevalence was lower in juveniles (3%) than adults (12%; P=0.03), and higher in in situ, captive-reared individuals (33%) than wild-born individuals (10%; P=0.005). Morphologic, analysis of microfilariae revealed they were neither D. immitis nor any other previously characterized North American species. PCR amplification of the 5S spacer region of rDNA revealed that the filarial sequence shared only 76% identity with D. immitis. This previously unidentified filarial sequence was present in all antigen positive animals (11 of 11 tested). It appears that black-footed ferrets were infected with a previously undescribed species of filaria whose antigen cross-reacted with the ELISA assay, although further analysis is needed to make a conclusive statement. Nonetheless, this previously undescribed filaria does not appear to threaten recovery for this highly endangered mammal

Differential MicroRNA Expression of miR-21 and miR-155 with Oral Cancer Extracellular Vesicles in Response to Melationin

Objective: Extracellular vesicles derived from oral cancer cells, which include Exosomes and Oncosomes, are membranous vesicles secreted into the surrounding extracellular environment. These extracellular vesicles can regulate and modulate oral squamous cell carcinoma (OSCC) progression through the horizontal transfer of bioactive molecules including proteins, lipids and microRNA (miRNA). The primary objective of this study was to examine the potential to isolate and evaluate extracellular vesicles (including exosomes) from various oral cancer cell lines and to explore potential differences in miRNA content. Methods: The OSCC cell lines SCC9, SCC25 and CAL27 were cultured in DMEM containing 10% exosome-free fetal bovine serum. Cell-culture conditioned media was collected for exosome and extracellular vesicle isolation after 72 h. Isolation was completed using the Total Exosome Isolation reagent (Invitrogen) and extracellular vesicle RNA was purified using the Total Exosome RNA isolation kit (Invitrogen). Extracellular vesicle miRNA content was evaluated using primers specific for miR-16, -21, -133a and -155. Results: Extracellular vesicles were successfully isolated from all three OSCC cell lines and total extracellular vesicle RNA was isolated. Molecular screening using primers specific for several miRNA revealed differential baseline expression among the different cell lines. The addition of melatonin significantly reduced the expression of miR-155 in all of the OSCC extracellular vesicles. However, miR-21 was significantly increased in each of the three OSCC isolates. No significant changes in miR-133a expression were observed under melatonin administration. Conclusions: Although many studies have documented changes in gene expression among various cancers under melatonin administration, few studies have evaluated these effects on microRNAs. These results may be among the first to evaluate the effects of melatonin on microRNA expression in oral cancers, which suggests the differential modulation of specific microRNAs, such as miR-21, miR-133a and miR-155, may be of significant importance when evaluating the mechanisms and pathways involved in melatonin-associated anti-tumor effects

Intimate partner violence perpetration and mental health service use in England: analysis of nationally representative survey data

Background Intimate partner violence perpetration (IPVP) is associated with psychiatric disorders, but an association with mental health service use has not been fully established and is relevant for policy. Mental health service contact by perpetrators of intimate partner violence presents an opportunity for reducing harmful behaviours. Aims To examine the association between IPVP and mental health service use. Method Analysis of national probability sample data from the 2014 Adult Psychiatric Morbidity Survey, testing for associations between lifetime IPVP and mental health service use. We assessed the impact of missing data with multiple imputation and examined misreporting using probabilistic bias analysis. Results The prevalence of reported lifetime IPVP was similar for men (8.0%) and women (8.6%). Before adjustments, IPVP was associated with mental health service use (odds ratio (OR) for any mental health service use in the past year for men: 2.8 (95% CI: 1.8–4.2), for women: 2.8 (95% CI: 2.1–3.8)). Adjustments for intimate partner violence victimisation and other life adversities had an attenuative influence. Associations remained on restricting comparisons with those without criminal justice involvement (OR for any mental health service use in the past year for men: 2.9 (95% CI: 1.7–4.8), for women: 2.3 (95% CI: 1.7–3.2)). Conclusion The strong association of IPVP with mental health service use is partly attributable to the concurrent presence of intimate partner violence victimisation and other life adversities. Efforts to improve the identification and assessment of IPVP in mental health services could benefit population health