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

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

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

Microbial nitrogen cycling in antarctic soils

The Antarctic continent is widely considered to be one of the most hostile biological habitats on Earth. Despite extreme environmental conditions, the ice-free areas of the continent, which constitute some 0.44% of the total continental land area, harbour substantial and diverse communities of macro-organisms and especially microorganisms, particularly in the more “hospitable” maritime regions. In the more extreme non-maritime regions, exemplified by the McMurdo Dry Valleys of South Victoria Land, nutrient cycling and ecosystem servicing processes in soils are largely driven by microbial communities. Nitrogen turnover is a cornerstone of ecosystem servicing. In Antarctic continental soils, specifically those lacking macrophytes, cold-active free-living diazotrophic microorganisms, particularly Cyanobacteria, are keystone taxa. The diazotrophs are complemented by heterotrophic bacterial and archaeal taxa which show the genetic capacity to perform elements of the entire N cycle, including nitrification processes such as the anammox reaction. Here, we review the current literature on nitrogen cycling genes, taxa, processes and rates from studies of Antarctic soils. In particular, we highlight the current gaps in our knowledge of the scale and contribution of these processes in south polar soils as critical data to underpin viable predictions of how such processes may alter under the impacts of future climate change.http://www.mdpi.com/journal/microorganismspm2020BiochemistryGeneticsMicrobiology and Plant Patholog

Biogeographical survey of soil microbiomes across sub-Saharan Africa:structure, drivers, and predicted climate-driven changes

BACKGROUND: Top-soil microbiomes make a vital contribution to the Earth’s ecology and harbor an extraordinarily high biodiversity. They are also key players in many ecosystem services, particularly in arid regions of the globe such as the African continent. While several recent studies have documented patterns in global soil microbial ecology, these are largely biased towards widely studied regions and rely on models to interpolate the microbial diversity of other regions where there is low data coverage. This is the case for sub-Saharan Africa, where the number of regional microbial studies is very low in comparison to other continents. RESULTS: The aim of this study was to conduct an extensive biogeographical survey of sub-Saharan Africa’s top-soil microbiomes, with a specific focus on investigating the environmental drivers of microbial ecology across the region. In this study, we sampled 810 sample sites across 9 sub-Saharan African countries and used taxonomic barcoding to profile the microbial ecology of these regions. Our results showed that the sub-Saharan nations included in the study harbor qualitatively distinguishable soil microbiomes. In addition, using soil chemistry and climatic data extracted from the same sites, we demonstrated that the top-soil microbiome is shaped by a broad range of environmental factors, most notably pH, precipitation, and temperature. Through the use of structural equation modeling, we also developed a model to predict how soil microbial biodiversity in sub-Saharan Africa might be affected by future climate change scenarios. This model predicted that the soil microbial biodiversity of countries such as Kenya will be negatively affected by increased temperatures and decreased precipitation, while the fungal biodiversity of Benin will benefit from the increase in annual precipitation. CONCLUSION: This study represents the most extensive biogeographical survey of sub-Saharan top-soil microbiomes to date. Importantly, this study has allowed us to identify countries in sub-Saharan Africa that might be particularly vulnerable to losses in soil microbial ecology and productivity due to climate change. Considering the reliance of many economies in the region on rain-fed agriculture, this study provides crucial information to support conservation efforts in the countries that will be most heavily impacted by climate change. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40168-022-01297-w

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.The National Research Foundation (NRF), the South African National Antarctic Program (SANAP 110717), the University of Pretoria, the Fulbright Visiting Scholar Program and the Biotechnology and Biological Sciences Research Council (BBSRC).https://msystems.asm.orgam2021BiochemistryGeneticsMicrobiology and Plant Patholog

Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches

New Precision Orbits of Bright Double-Lined Spectroscopic Binaries. I: RR Lyncis, 12 Bootis, and HR 6169

Radial velocities from the 2.1 m telescope at McDonald Observatory supplemented with radial velocities from the coude' feed telescope at KPNO provide new precise orbits for the double-lined spectroscopic binaries RR Lyn (A3/A8/A6), 12 Boo (F8IV), and HR 6169 (A2V). We derive orbital dimensions and minimum masses with accuracies of 0.06 to 0.9 %. The three systems, which have V magnitudes of 5.54, 4.83, and 6.42, respectively, are all sufficiently bright that they are easily within the grasp of modern optical interferometers and so afford the prospect, when our spectroscopic observations are complemented by interferometric observations, of fully-determined orbits, precise masses, and distances. In the case of RR Lyn, which is also a detached eclipsing binary with a well-determined orbital inclination, we are able to determine the semimajor axis of the relative orbit, a = 29.32 +/- 0.04 Rsun, primary and secondary radii of 2.57 +/- 0.02 Rsun and 1.59 +/- 0.03 Rsun, respectively; and primary and secondary masses of 1.927 +/- 0.008 Msun and 1.507 +/- 0.004 Msun, respectively. Comparison of our new systemic velocity determination, gamma = -12.03 +/- 0.04 km/s, with an earlier one, gamma = -11.61 +/- 0.30 km/s, shows no evidence of any change in the systemic velocity in the 40 years separating the two measurements, a null result that neither confirms nor contradicts the presence of the low-mass third component proposed by Khaliullin & Khaliullina (2002). Our spectroscopic orbit of 12 Boo is more precise that that of Boden et al. (2005), but confirms their results about this system. Our analysis of HR 6169 has produced a major improvement in its orbital elements. The minimum masses of the primary and secondary are 2.20 +/- 0.01 and 1.64 +/- 0.02 Msun, respectively.Comment: To appear in the May A

Clinical Utility of a Unique Genome-Wide DNA Methylation Signature for KMT2A-Related Syndrome

Wiedemann\u2013Steiner syndrome (WDSTS) is a Mendelian syndromic intellectual disability (ID) condition associated with hypertrichosis cubiti, short stature, and characteristic facies caused by pathogenic variants in the KMT2A gene. Clinical features can be inconclusive in mild and unusual WDSTS presentations with variable ID (mild to severe), facies (typical or not) and other associated malformations (bone, cerebral, renal, cardiac and ophthalmological anomalies). Interpretation and classification of rare KMT2A variants can be challenging. A genome-wide DNA methylation episignature for KMT2A-related syndrome could allow functional classification of variants and provide insights into the pathophysiology of WDSTS. Therefore, we assessed genome-wide DNA methylation profiles in a cohort of 60 patients with clinical diagnosis for WDSTS or Kabuki and identified a unique highly sensitive and specific DNA methylation episignature as a molecular biomarker of WDSTS. WDSTS episignature enabled classification of variants of uncertain significance in the KMT2A gene as well as confirmation of diagnosis in patients with clinical presentation of WDSTS without known genetic variants. The changes in the methylation profile resulting from KMT2A mutations involve global reduction in methylation in various genes, including homeobox gene promoters. These findings provide novel insights into the molecular etiology of WDSTS and explain the broad phenotypic spectrum of the disease