Inference of Temporally Varying Bayesian Networks

When analysing gene expression time series data an often overlooked but crucial aspect of the model is that the regulatory network structure may change over time. Whilst some approaches have addressed this problem previously in the literature, many are not well suited to the sequential nature of the data. Here we present a method that allows us to infer regulatory network structures that may vary between time points, utilising a set of hidden states that describe the network structure at a given time point. To model the distribution of the hidden states we have applied the Hierarchical Dirichlet Process Hideen Markov Model, a nonparametric extension of the traditional Hidden Markov Model, that does not require us to fix the number of hidden states in advance. We apply our method to exisiting microarray expression data as well as demonstrating is efficacy on simulated test data

Echelle long-slit optical spectroscopy of evolved stars

We present echelle long-slit optical spectra of a sample of objects evolving off the AGB, most of them in the pre-planetary nebula (pPN) phase, obtained with the ESI and MIKE spectrographs at Keck-II and Magellan-I, respectively. The total wavelength range covered with ESI (MIKE) is ~3900 to 10900 A (~3600 to 7200A). In this paper, we focus our analysis mainly on the Halpha profiles. Prominent Halpha emission is detected in half of the objects, most of which show broad Halpha wings (up to ~4000 km/s). In the majority of the Halpha-emission sources, fast, post-AGB winds are revealed by P-Cygni profiles. In ~37% of the objects Halpha is observed in absorption. In almost all cases, the absorption profile is partially filled with emission, leading to complex, structured profiles that are interpreted as an indication of incipient post-AGB mass-loss. All sources in which Halpha is seen mainly in absorption have F-G type central stars, whereas sources with intense Halpha emission span a larger range of spectral types from O to G. Shocks may be an important excitation agent of the close stellar surroundings for objects with late type central stars. Sources with pure emission or P Cygni Halpha profiles have larger J-K color excess than objects with Halpha mainly in absorption, which suggests the presence of warm dust near the star in the former. The two classes of profile sources also segregate in the IRAS color-color diagram in a way that intense Halpha-emitters have dust grains with a larger range of temperatures. (abridged)Comment: 68 pages, 14 figures, accepted for publication in ApJS (abstract abridged

GlacialWater: A Dynamic Microbial Medium

Microbial communities and nutrient dynamics in glaciers and ice sheets continuously change as the hydrological conditions within and on the ice change. Glaciers and ice sheets can be considered bioreactors as microbiomes transform nutrients that enter these icy systems and alter the meltwater chemistry. Global warming is increasing meltwater discharge, affecting nutrient and cell export, and altering proglacial systems. In this review, we integrate the current understanding of glacial hydrology, microbial activity, and nutrient and carbon dynamics to highlight their interdependence and variability on daily and seasonal time scales, as well as their impact on proglacial environments

Enumeration and phenotypical analysis of distinct dendritic cell subsets in psoriatic arthritis and rheumatoid arthritis

Dendritic cells (DCs) comprise heterogeneous subsets of professional antigen-presenting cells, linking innate and adaptive immunity. Analysis of DC subsets has been hampered by a lack of specific DC markers and reliable quantitation assays. We characterised the immunophenotype and functional characteristics of psoriatic arthritis (PsA)-derived and rheumatoid arthritis (RA)-derived myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) to evaluate their potential role in arthritis. Circulating peripheral blood (PB) pDC numbers were significantly reduced in PsA patients (P = 0.0098) and RA patients (P = 0.0194), and mDCs were significantly reduced in RA patients (P = 0.0086) compared with healthy controls. The number of circulating mDCs in RA PB was significantly inversely correlated to C-reactive protein (P = 0.021). The phenotype of both DC subsets in PsA PB and RA PB was immature as compared with healthy controls. Moreover, CD62L expression was significantly decreased on both mDCs (PsA, P = 0.0122; RA, P = 0.0371) and pDCs (PsA, P = 0.0373; RA, P = 0.0367) in PB. Both mDCs and pDCs were present in PsA synovial fluid (SF) and RA SF, with the mDC:pDC ratio significantly exceeding that in matched PB (PsA SF, P = 0.0453; RA SF, P = 0.0082). pDCs isolated from RA SF and PsA SF displayed an immature phenotype comparable with PB pDCs. RA and PsA SF mDCs, however, displayed a more mature phenotype (increased expression of CD80, CD83 and CD86) compared with PB mDCs. Functional analysis revealed that both SF DC subsets matured following toll-like receptor stimulation. pDCs from PB and SF produced interferon alpha and tumour necrosis factor alpha on TLR9 stimulation, but only SF pDCs produced IL-10. Similarly, mDCs from PB and SF produced similar tumour necrosis factor alpha levels to TLR2 agonism, whereas SF mDCs produced more IL-10 than PB controls. Circulating DC subset numbers are reduced in RA PB and PsA PB with reduced CD62L expression. Maturation is incomplete in the inflamed synovial compartment. Immature DCs in SF may contribute to the perpetuation of inflammation via sampling of the inflamed synovial environment, and in situ presentation of arthritogenic antigen

The multi-risk vulnerability of global coal regions in the context of mine closure

Coal mining industries face real challenges to meet legal demands on a low carbon future. The history of coal in industrial transitions seems to come to a rapid end, accompanied by widespread boom of closing active coal mining projects. This change can result in negative ramifications for coal mining regions, involving a complex interplay of multiple risks. In this paper, we aim to analyse the complexity of environmental, social, and governance factors that can cause significant difficulties in closure of coal mining operations. We identify multi-factor risk profiles for operating mines by applying spatially explicit indicators within a proposed multi-risk framework. The indicators have not been captured by conventional market, as they tend to be more long-term oriented in the context of strategy and performance. We map eight risk categories: stability, water and climate, biodiversity, vulnerability of land uses, indigenous people, social fragility, political fragility, and regulatory environment, and analyse their effect on a global dataset of active open pit coal mines. The spatial analysis reveals that a significant proportion of the projects face accumulation of multiple risk factors. A total of 552 projects out of 916 show medium to very high-risk occurrence. In this paper, we present global risk vulnerability across the coal mining projects by indicating extent to which operators of the mines face multiple risk factors when planning for closure

Three Wide-Separation L dwarf Companions from the Two Micron All Sky Survey: Gl 337C, Gl 618.1B, and HD 89744B

We present two confirmed wide separation L-dwarf common proper motion companions to nearby stars and one candidate identified from the Two Micron All Sky Survey. Spectral types from optical spectroscopy are L0 V, L2.5 V, and L8 V. Near-infrared low resolution spectra of the companions are provided as well as a grid of known objects spanning M6 V -- T dwarfs to support spectral type assignment for these and future L-dwarfs in the z'JHK bands. Using published measurements, we estimate ages of the companions from physical properties of the primaries. These crude ages allow us to estimate companion masses using theoretical low-mass star and brown dwarf evolutionary models. The new L-dwarfs in this paper bring the number of known wide-binary (Separation >= 100 AU) L-dwarf companions of nearby stars to nine. One of the L-dwarfs is a wide separation companion to the F7 IV-V + extrasolar planet system HD89744Ab.Comment: 20 pages including 6 tables and 4 figures, AJ, in pres

Heterogeneous expression pattern of interleukin 17A (IL-17A), IL-17F and their receptors in synovium of rheumatoid arthritis, psoriatic arthritis and osteoarthritis: possible explanation for nonresponse to anti-IL-17 therapy?

Accumulating evidence suggests an important role for interleukin 17 (IL-17) in the pathogenesis of several inflammatory diseases, including rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Accordingly, clinical trials aimed at blocking IL-17 have been initiated, but clinical results between patients and across different diseases have been highly variable. The objective was to determine the variability in expression of IL-17A, IL-17F and their receptors IL-17RA and IL-17RC in the synovia of patients with arthritis. Synovial biopsies were obtained from patients with RA (n = 11), PsA (n = 15) and inflammatory osteoarthritis (OA, n = 14). For comparison, synovia from noninflamed knee joints (n = 7) obtained from controls were included. Frozen sections were stained for IL-17A, IL-17F, IL-17RA and IL-17RC and evaluated by digital image analysis. We used confocal microscopy to determine which cells in the synovium express IL-17A and IL-17F, double-staining with CD4, CD8, CD15, CD68, CD163, CD31, von Willebrand factor, peripheral lymph node address in, lymphatic vessel endothelial hyaluronan receptor 1, mast cell tryptase and retinoic acid receptor-related orphan receptor γt (RORγt). IL-17A, IL-17F, IL-17RA and IL-17RC were abundantly expressed in synovial tissues of all patient groups. Whereas IL-17RA was present mostly in the synovial sublining, IL-17RC was abundantly expressed in the intimal lining layer. Digital image analysis showed a significant (P  < 0.05) increase of only IL-17A in arthritis patients compared to noninflamed control tissues. The expression of IL-17A, IL-17F and their receptors was similar in the different patient groups, but highly variable between individual patients. CD4+ and CD8+ cells coexpressed IL-17A, and few cells coexpressed IL-17F. IL-17A and IL-17F were not expressed by CD15+ neutrophils. Mast cells were only occasionally positive for IL-17A or IL-17F. Interestingly, IL-17A and IL-17F staining was also observed in macrophages, as well as in blood vessels and lymphatics. This staining probably reflects receptor-bound cytokine staining. Many infiltrated cells were positive for the transcription factor RORγt. Colocalisation between RORγt and IL-17A and IL-17F indicates local IL-17 production. Increased expression of IL-17A is not restricted to synovial tissues of RA and PsA patients; it is also observed in inflammatory OA. The heterogeneous expression levels may explain nonresponse to anti-IL-17 therapy in subsets of patient

Phages actively challenge niche communities in Antarctic soils

By modulating the structure, diversity, and trophic outputs of microbial communities, phages play crucial roles in many biomes. In oligotrophic polar deserts, the effects of katabatic winds, constrained nutrients, and low water availability are known to limit microbial activity. Although phages may substantially govern trophic interactions in cold deserts, relatively little is known regarding the precise ecological mechanisms. Here, we provide the first evidence of widespread antiphage innate immunity in Antarctic environments using metagenomic sequence data from hypolith communities as model systems. In particular, immunity systems such as DISARM and BREX are shown to be dominant systems in these communities. Additionally, we show a direct correlation between the CRISPR-Cas adaptive immunity and the metavirome of hypolith communities, suggesting the existence of dynamic host-phage interactions. In addition to providing the first exploration of immune systems in cold deserts, our results suggest that phages actively challenge niche communities in Antarctic polar deserts. We provide evidence suggesting that the regulatory role played by phages in this system is an important determinant of bacterial host interactions in this environment. IMPORTANCE In Antarctic environments, the combination of both abiotic and biotic stressors results in simple trophic levels dominated by microbiomes. Although the past two decades have revealed substantial insights regarding the diversity and structure of microbiomes, we lack mechanistic insights regarding community interactions and how phages may affect these. By providing the first evidence of widespread antiphage innate immunity, we shed light on phage-host dynamics in Antarctic niche communities. Our analyses reveal several antiphage defense systems, including DISARM and BREX, which appear to dominate in cold desert niche communities. In contrast, our analyses revealed that genes which encode antiphage adaptive immunity were underrepresented in these communities, suggesting lower infection frequencies in cold edaphic environments. We propose that by actively challenging niche communities, phages play crucial roles in the diversification of Antarctic communities