Normal levels of p27Xic1 are necessary for somite segmentation and determining pronephric organ size

The Xenopus laevis cyclin dependent kinase inhibitor p27Xic1 has been shown to be involved in exit from the cell cycle and differentiation of cells into a quiescent state in the nervous system, muscle tissue, heart and retina. We show that p27Xic1 is expressed in the developing kidney in the nephrostomal regions. Using over-expression and morpholino oligonucleotide (MO) knock-down approaches we show normal levels of p27Xic1 regulate pronephros organ size by regulating cell cycle exit. Knock-down of p27Xic1 expression using a MO prevented myogenesis, as previously reported; an effect that subsequently inhibits pronephrogenesis. Furthermore, we show that normal levels of p27Xic1 are required for somite segmentation also through its cell cycle control function. Finally, we provide evidence to suggest correct paraxial mesoderm segmentation is not necessary for pronephric induction in the intermediate mesoderm. These results indicate novel developmental roles for p27Xic1, and reveal its differentiation function is not universally utilised in all developing tissues

Genetic architecture of sporadic frontotemporal dementia and overlap with Alzheimer's and Parkinson's diseases

BACKGROUND: Clinical, pathological and genetic overlap between sporadic frontotemporal dementia (FTD), Alzheimer's disease (AD) and Parkinson's disease (PD) has been suggested; however, the relationship between these disorders is still not well understood. Here we evaluated genetic overlap between FTD, AD and PD to assess shared pathobiology and identify novel genetic variants associated with increased risk for FTD. METHODS: Summary statistics were obtained from the International FTD Genomics Consortium, International PD Genetics Consortium and International Genomics of AD Project (n>75 000 cases and controls). We used conjunction false discovery rate (FDR) to evaluate genetic pleiotropy and conditional FDR to identify novel FTD-associated SNPs. Relevant variants were further evaluated for expression quantitative loci. RESULTS: We observed SNPs within the HLA, MAPT and APOE regions jointly contributing to increased risk for FTD and AD or PD. By conditioning on polymorphisms associated with PD and AD, we found 11 loci associated with increased risk for FTD. Meta-analysis across two independent FTD cohorts revealed a genome-wide signal within the APOE region (rs6857, 3′-UTR=PVRL2, p=2.21×10–12), and a suggestive signal for rs1358071 within the MAPT region (intronic=CRHR1, p=4.91×10−7) with the effect allele tagging the H1 haplotype. Pleiotropic SNPs at the HLA and MAPT loci associated with expression changes in cis-genes supporting involvement of intracellular vesicular trafficking, immune response and endo/lysosomal processes. CONCLUSIONS: Our findings demonstrate genetic pleiotropy in these neurodegenerative diseases and indicate that sporadic FTD is a polygenic disorder where multiple pleiotropic loci with small effects contribute to increased disease risk

Transcription profiling reveals potential mechanisms of dysbiosis in the oral microbiome of rhesus macaques with chronic untreated SIV infection.

A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Due to the impracticalities of conducting host-microbe systems-based studies in HIV infected patients, we have evaluated the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. We present the first description of the rhesus macaque oral microbiota and show that a mixture of human commensal bacteria and "macaque versions" of human commensals colonize the tongue dorsum and dental plaque. Our findings indicate that SIV infection results in chronic activation of antiviral and inflammatory responses in the tongue mucosa that may collectively lead to repression of epithelial development and impact the microbiome. In addition, we show that dysbiosis of the lingual microbiome in SIV infection is characterized by outgrowth of Gemella morbillorum that may result from impaired macrophage function. Finally, we provide evidence that the increased capacity of opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated with reduced production of antimicrobial peptides

Localisation of RNAs into the germ plasm of vitellogenic xenopus oocytes

We have studied the localisation of mRNAs in full-grown Xenopus laevis oocytes by injecting fluorescent RNAs, followed by confocal microscopy of the oocyte cortex. Concentrating on RNA encoding the Xenopus Nanos homologue, nanos1 (formerly Xcat2), we find that it consistently localised into aggregated germ plasm ribonucleoprotein (RNP) particles, independently of cytoskeletal integrity. This implies that a diffusion/entrapment-mediated mechanism is active, as previously reported for previtellogenic oocytes. Sometimes this was accompanied by localisation into scattered particles of the “late”, Vg1/VegT pathway; occasionally only late pathway localisation was seen. The Xpat RNA behaved in an identical fashion and for neither RNA was the localisation changed by any culture conditions tested. The identity of the labelled RNP aggregates as definitive germ plasm was confirmed by their inclusion of abundant mitochondria and co-localisation with the germ plasm protein Hermes. Further, the nanos1/Hermes RNP particles are interspersed with those containing the germ plasm protein Xpat. These aggregates may be followed into the germ plasm of unfertilized eggs, but with a notable reduction in its quantity, both in terms of injected molecules and endogenous structures. Our results conflict with previous reports that there is no RNA localisation in large oocytes, and that during mid-oogenesis even germ plasm RNAs localise exclusively by the late pathway. We find that in mid oogenesis nanos1 RNA also localises to germ plasm but also by the late pathway. Late pathway RNAs, Vg1 and VegT, also may localise into germ plasm. Our results support the view that mechanistically the two modes of localisation are extremely similar, and that in an injection experiment RNAs might utilise either pathway, the distinction in fates being very subtle and subject to variation. We discuss these results in relation to their biological significance and the results of others

Adolescent brain maturation and cortical folding: evidence for reductions in gyrification

Evidence from anatomical and functional imaging studies have highlighted major modifications of cortical circuits during adolescence. These include reductions of gray matter (GM), increases in the myelination of cortico-cortical connections and changes in the architecture of large-scale cortical networks. It is currently unclear, however, how the ongoing developmental processes impact upon the folding of the cerebral cortex and how changes in gyrification relate to maturation of GM/WM-volume, thickness and surface area. In the current study, we acquired high-resolution (3 Tesla) magnetic resonance imaging (MRI) data from 79 healthy subjects (34 males and 45 females) between the ages of 12 and 23 years and performed whole brain analysis of cortical folding patterns with the gyrification index (GI). In addition to GI-values, we obtained estimates of cortical thickness, surface area, GM and white matter (WM) volume which permitted correlations with changes in gyrification. Our data show pronounced and widespread reductions in GI-values during adolescence in several cortical regions which include precentral, temporal and frontal areas. Decreases in gyrification overlap only partially with changes in the thickness, volume and surface of GM and were characterized overall by a linear developmental trajectory. Our data suggest that the observed reductions in GI-values represent an additional, important modification of the cerebral cortex during late brain maturation which may be related to cognitive development

The gas morphology of nearby star-forming galaxies

A galaxya-s morphology stems from the secular and environmental processes taking place over the course of its evolutionary history. Thus, it has consistently served as an important tool for gaining insights into galaxy evolution. In this work, we visually classified morphologies on cloud-scales based on the molecular gas distribution of a large sample of 79 nearby main sequence galaxies, using 1a-3; resolution CO(2a-1) ALMA observations taken as part of the PHANGS survey. For this purpose, we devised a morphology classification scheme for different types of bars, spiral arms (grand-design, flocculent, multi-Arm and smooth), and rings (central and non-central rings) that are similar to the well established optical ones. Furthermore, we introduced bar lane classes. In general, our cold gas-based morphologies is in good agreement with the ones based on stellar light. Both of our bars, as well as the grand-design spiral arms, are preferentially found at the higher mass end of our sample. Our gas-based classification indicates a potential for a misidentification of unbarred galaxies in the optical when massive star formation is present. Central or nuclear rings are present in a third of the sample, with a strong preference seen for barred galaxies (59%). As stellar bars are present in 45a-±a-5% of our sample galaxies, we explore the utility of molecular gas as tracer of bar lane properties. We find that more curved bar lanes have a shorter radial extent in molecular gas and reside in galaxies with lower molecular to stellar mass ratios than those with straighter geometries. Galaxies display a wide range of CO morphologies and this work is aimed at providing a catalogue of morphological features in a representative sample of nearby galaxies

The census as an information source in public policy-making

This paper provides an assessment of the value of national population censuses as information sources with specific reference toUK census data and its use in policy-making. Mixed methods were adopted to collect quantitative and qualitative data from twosources: (1) a content analysis of policy documents, and (2) interviews with policy-makers in Scotland. The findings highlight thatalthough the general value of the census is recognised, policy-makers are not necessarily closely engaged with the census as a toolfor directing the development and implementation of policy. This is evident, for example in a lack of awareness of proposed changesto the census, and infrequent deployment of available data. The opportunity to change perceptions among policy-makers, and toexpand the application of census data in public policy, is identified. With a novel focus on the deployment of censuses as sources ofevidence for policy-making that includes the views of policy-makers from both within and beyond government, this workcontributes to an established body of global research on international censuses

Genetic pleiotropy between multiple sclerosis and schizophrenia but not bipolar disorder : differential involvement of immune-related gene loci

J. Saarela työryhmäjäsen.Peer reviewe

Sub-kiloparsec empirical relations and excitation conditions of HCN and HCO+ J=3-2 in nearby star-forming galaxies

We present new HCN and HCO+ (J = 3–2) images of the nearby star-forming galaxies (SFGs) NGC 3351, NGC 3627, and NGC 4321. The observations, obtained with the Morita ALMA Compact Array, have a spatial resolution of ∼290–440 pc and resolve the inner Rgal ≲ 0.6–1 kpc of the targets, as well as the southern bar end of NGC 3627. We complement this data set with publicly available images of lower excitation lines of HCN, HCO+, and CO and analyse the behaviour of a representative set of line ratios: HCN(3–2)/HCN(1–0), HCN(3–2)/HCO+(3–2), HCN(1–0)/CO(2–1), and HCN(3–2)/CO(2–1). Most of these ratios peak at the galaxy centres and decrease outwards. We compare the HCN and HCO+ observations with a grid of one-phase, non-local thermodynamic equilibrium (non-LTE) radiative transfer models and find them compatible with models that predict subthermally excited and optically thick lines. We study the systematic variations of the line ratios across the targets as a function of the stellar surface density (Σstar), the intensity-weighted CO(2–1) (⟨ICO⟩), and the star formation rate surface density (ΣSFR). We find no apparent correlation with ΣSFR, but positive correlations with the other two parameters, which are stronger in the case of ⟨ICO⟩. The HCN/CO–⟨ICO⟩ relations show ≲0.3 dex galaxy-to-galaxy offsets, with HCN(3–2)/CO(2–1)–⟨ICO⟩ being ∼2 times steeper than HCN(1–0)/CO(2–1). In contrast, the HCN(3–2)/HCN(1–0)–⟨ICO⟩ relation exhibits a tighter alignment between galaxies. We conclude that the overall behaviour of the line ratios cannot be ascribed to variations in a single excitation parameter (e.g., density or temperature)

Impacts of climate change on plant diseases – opinions and trends

There has been a remarkable scientific output on the topic of how climate change is likely to affect plant diseases in the coming decades. This review addresses the need for review of this burgeoning literature by summarizing opinions of previous reviews and trends in recent studies on the impacts of climate change on plant health. Sudden Oak Death is used as an introductory case study: Californian forests could become even more susceptible to this emerging plant disease, if spring precipitations will be accompanied by warmer temperatures, although climate shifts may also affect the current synchronicity between host cambium activity and pathogen colonization rate. A summary of observed and predicted climate changes, as well as of direct effects of climate change on pathosystems, is provided. Prediction and management of climate change effects on plant health are complicated by indirect effects and the interactions with global change drivers. Uncertainty in models of plant disease development under climate change calls for a diversity of management strategies, from more participatory approaches to interdisciplinary science. Involvement of stakeholders and scientists from outside plant pathology shows the importance of trade-offs, for example in the land-sharing vs. sparing debate. Further research is needed on climate change and plant health in mountain, boreal, Mediterranean and tropical regions, with multiple climate change factors and scenarios (including our responses to it, e.g. the assisted migration of plants), in relation to endophytes, viruses and mycorrhiza, using long-term and large-scale datasets and considering various plant disease control methods