A versatile palindromic amphipathic repeat coding sequence horizontally distributed among diverse bacterial and eucaryotic microbes

<p>Abstract</p> <p>Background</p> <p>Intragenic tandem repeats occur throughout all domains of life and impart functional and structural variability to diverse translation products. Repeat proteins confer distinctive surface phenotypes to many unicellular organisms, including those with minimal genomes such as the wall-less bacterial monoderms, <it>Mollicutes</it>. One such repeat pattern in this clade is distributed in a manner suggesting its exchange by horizontal gene transfer (HGT). Expanding genome sequence databases reveal the pattern in a widening range of bacteria, and recently among eucaryotic microbes. We examined the genomic flux and consequences of the motif by determining its distribution, predicted structural features and association with membrane-targeted proteins.</p> <p>Results</p> <p>Using a refined hidden Markov model, we document a 25-residue protein sequence motif tandemly arrayed in variable-number repeats in ORFs lacking assigned functions. It appears sporadically in unicellular microbes from disparate bacterial and eucaryotic clades, representing diverse lifestyles and ecological niches that include host parasitic, marine and extreme environments. Tracts of the repeats predict a malleable configuration of recurring domains, with conserved hydrophobic residues forming an amphipathic secondary structure in which hydrophilic residues endow extensive sequence variation. Many ORFs with these domains also have membrane-targeting sequences that predict assorted topologies; others may comprise reservoirs of sequence variants. We demonstrate expressed variants among surface lipoproteins that distinguish closely related animal pathogens belonging to a subgroup of the <it>Mollicutes</it>. DNA sequences encoding the tandem domains display dyad symmetry. Moreover, in some taxa the domains occur in ORFs selectively associated with mobile elements. These features, a punctate phylogenetic distribution, and different patterns of dispersal in genomes of related taxa, suggest that the repeat may be disseminated by HGT and intra-genomic shuffling.</p> <p>Conclusions</p> <p>We describe novel features of PARCELs (<b>P</b>alindromic <b>A</b>mphipathic <b>R</b>epeat <b>C</b>oding <b>EL</b>ements), a set of widely distributed repeat protein domains and coding sequences that were likely acquired through HGT by diverse unicellular microbes, further mobilized and diversified within genomes, and co-opted for expression in the membrane proteome of some taxa. Disseminated by multiple gene-centric vehicles, ORFs harboring these elements enhance accessory gene pools as part of the "mobilome" connecting genomes of various clades, in taxa sharing common niches.</p

The Max-Planck-Institute global ocean/sea ice model with orthogonal curvilinear coordinates

The Hamburg Ocean Primitive Equation model has undergone significant development in recent years. Most notable is the treatment of horizontal discretisation which has undergone transition from a staggered E-grid to an orthogonal curvilinear C-grid. The treatment of subgridscale mixing has been improved by the inclusion of a new formulation of bottom boundary layer (BBL) slope convection, an isopycnal diffusion scheme, and a Gent and McWilliams style eddy-induced mixing parameterisation. The model setup described here has a north pole over Greenland and a south pole on the coast of the Weddell Sea. This gives relatively high resolution in the sinking regions associated with the thermohaline circulation. Results are presented from a 450 year climatologically forced integration. The forcing is a product of the German Ocean Model Intercomparison Project and is derived from the European Centre for Medium Range Weather Forecasting reanalysis. The main emphasis is on the model's representation of key quantities that are easily associated with the ocean's role in the global climate system. The global and Atlantic northward poleward heat transports have peaks of 1.43 and 0.84 PW, at 18degrees and 21degrees N respectively. The Atlantic meridional overturning streamfunction has a peak of 15.7 Sv in the North Atlantic and an outflow of 11.9 Sv at 30degrees S. Comparison with a simulation excluding BBL shows that the scheme is responsible for up to a 25% increase in North Atlantic heat transport, with significant improvement of the depths of convection in the Greenland, Labrador and Irminger Seas. Despite the improvements, comparison with observations shows the heat transport still to be too weak. Other outstanding problems include an incorrect Gulf Stream pathway, a too strong Antarctic Circumpolar Current, and a too weak renewal of Antarctic Intermediate Water. Nevertheless, the model has been coupled to the atmospheric GCM ECHAM5 and run successfully for over 250 years without any surface flux corrections. (C) 2002 Elsevier Science Ltd. All rights reserved

Histone deacetylases 1, 2 and 3 are highly expressed in prostate cancer and HDAC2 expression is associated with shorter PSA relapse time after radical prostatectomy

High activity of histone deacetylases (HDACs) causes epigenetic alterations associated with malignant cell behaviour. Consequently, HDAC inhibitors have entered late-phase clinical trials as new antineoplastic drugs. However, little is known about expression and function of specific HDAC isoforms in human tumours including prostate cancer. We investigated the expression of class I HDACs in 192 prostate carcinomas by immunohistochemistry and correlated our findings to clinicopathological parameters including follow-up data. Class I HDAC isoforms were strongly expressed in the majority of the cases (HDAC1: 69.8%, HDAC2: 74%, HDAC3: 94.8%). High rates of HDAC1 and HDAC2 expression were significantly associated with tumour dedifferentiation. Strong expression of all HDACs was accompanied by enhanced tumour cell proliferation. In addition, HDAC2 was an independent prognostic marker in our prostate cancer cohort. In conclusion, we showed that the known effects of HDACs on differentiation and proliferation of cancer cells observed in vitro can also be confirmed in vivo. The class I HDAC isoforms 1, 2 and 3 are differentially expressed in prostate cancer, which might be important for upcoming studies on HDAC inhibitors in this tumour entity. Also, the highly significant prognostic value of HDAC2 clearly deserves further study

Enhancing methane production from lignocellulosic biomass by combined steam‑explosion pretreatment and bioaugmentation with cellulolytic bacterium Caldicellulosiruptor bescii

Background: Biogas production from lignocellulosic biomass is generally considered to be challenging due to the recalcitrant nature of this biomass. In this study, the recalcitrance of birch was reduced by applying steam-explosion (SE) pretreatment (210 °C and 10 min). Moreover, bioaugmentation with the cellulolytic bacterium Caldicellulosiruptor bescii was applied to possibly enhance the methane production from steam-exploded birch in an anaerobic digestion (AD) process under thermophilic conditions (62 °C). Results: Overall, the combined SE and bioaugmentation enhanced the methane yield up to 140% compared to untreated birch, while SE alone contributed to the major share of methane enhancement by 118%. The best methane improvement of 140% on day 50 was observed in bottles fed with pretreated birch and bioaugmentation with lower dosages of C. bescii (2 and 5% of inoculum volume). The maximum methane production rate also increased from 4-mL CH4/ g VS (volatile solids)/day for untreated birch to 9-14-mL CH4/ g VS/day for steam-exploded birch with applied bioaugmentation. Bioaugmentation was particularly effective for increasing the initial methane production rate of the pretreated birch yielding 21-44% more methane than the pretreated birch without applied bioaugmentation. The extent of solubilization of the organic matter was increased by more than twofold when combined SE pretreatment and bioaugmentation was used in comparison with the methane production from untreated birch. The beneficial effects of SE and bioaugmentation on methane yield indicated that biomass recalcitrance and hydrolysis step are the limiting factors for efficient AD of lignocellulosic biomass. Microbial community analysis by 16S rRNA amplicon sequencing showed that the microbial community composition was altered by the pretreatment and bioaugmentation processes. Notably, the enhanced methane production by pretreatment and bioaugmentation was well correlated with the increase in abundance of key bacterial and archaeal communities, particularly the hydrolytic bacterium Caldicoprobacter, several members of syntrophic acetate oxidizing bacteria and the hydrogenotrophic Methanothermobacter. Conclusion: Our findings demonstrate the potential of combined SE and bioaugmentation for enhancing methane production from lignocellulosic biomass

Serum IL-6, sAXL, and YKL-40 as systemic correlates of reduced brain structure and function in Alzheimer’s disease: results from the DELCODE study

Background Neuroinflammation constitutes a pathological hallmark of Alzheimer’s disease (AD). Still, it remains unresolved if peripheral inflammatory markers can be utilized for research purposes similar to blood-based beta-amyloid and neurodegeneration measures. We investigated experimental inflammation markers in serum and analyzed interrelations towards AD pathology features in a cohort with a focus on at-risk stages of AD. Methods Data of 74 healthy controls (HC), 99 subjective cognitive decline (SCD), 75 mild cognitive impairment (MCI), 23 AD relatives, and 38 AD subjects were obtained from the DELCODE cohort. A panel of 20 serum biomarkers was determined using immunoassays. Analyses were adjusted for age, sex, APOE status, and body mass index and included correlations between serum and CSF marker levels and AD biomarker levels. Group-wise comparisons were based on screening diagnosis and routine AD biomarker-based schematics. Structural imaging data were combined into composite scores representing Braak stage regions and related to serum biomarker levels. The Preclinical Alzheimer’s Cognitive Composite (PACC5) score was used to test for associations between the biomarkers and cognitive performance. Results Each experimental marker displayed an individual profile of interrelations to AD biomarkers, imaging, or cognition features. Serum-soluble AXL (sAXL), IL-6, and YKL-40 showed the most striking associations. Soluble AXL was significantly elevated in AD subjects with pathological CSF beta-amyloid/tau profile and negatively related to structural imaging and cognitive function. Serum IL-6 was negatively correlated to structural measures of Braak regions, without associations to corresponding IL-6 CSF levels or other AD features. Serum YKL-40 correlated most consistently to CSF AD biomarker profiles and showed the strongest negative relations to structure, but none to cognitive outcomes. Conclusions Serum sAXL, IL-6, and YKL-40 relate to different AD features, including the degree of neuropathology and cognitive functioning. This may suggest that peripheral blood signatures correspond to specific stages of the disease. As serum markers did not reflect the corresponding CSF protein levels, our data highlight the need to interpret serum inflammatory markers depending on the respective protein’s specific biology and cellular origin. These marker-specific differences will have to be considered to further define and interpret blood-based inflammatory profiles for AD research

A global heat and freshwater forcing dataset for ocean models

A global dataset based on the ECMWF Re-Analyses (ERA) is presented that can be used as surface boundary conditions for ocean models with sea-ice components. The definition of these conditions is based on bulk formulae. To study the mean ocean circulation, a mean annual cycle on a daily basis was constructed from ERA for all relevant parameters including wind stress. Continental runoff is considered by using information about the catchment areas of the rivers and about the main drainage basins. The bulk formulae were extended by using sea ice concentration. To estimate meridional heat transports (MHT) and to avoid any drift in ocean model simulations, the heat and fresh water budgets have been closed by applying an inverse procedure to fine-tune the fluxes towards observed transports. To improve the MHTs on the Southern Hemisphere the winds and the short wave radiation at southern higher latitudes should be corrected. Furthermore, tests were performed concerning short wave radiation which was increased in the tropics and decreased in the subsidence zones. The heat and fresh water fluxes are assessed by using a scheme of Macdonald and Wunsch based on hydrographic sections. The net heat fluxes of ERA and of the forcing dataset are consistent with the heat flux divergences and convergences estimated by this scheme except for parts of the South Atlantic and the Indian Ocean sector of the Southern Ocean where none of these datasets is consistent with these estimates. In the subtropical South Indian Ocean the forcing dataset is consistent with these estimates while ERA are not. The flux components of ERA and the forcing dataset were compared to several observational datasets (SRB, SOC, HOAPS, GPCP, and CMAP). For each component, at least one of these datasets (especially HOAPS) supports the effects of the inverse procedure and the bulk formulae almost globally with some regional exceptions: short wave radiation in the tropical oceans and the subtropical North Atlantic, latent heat flux at higher latitudes, and precipitation in the northern North Atlantic. [References: 99

Global oceanic heat and fresh water forcing datasets based on ERA-40 and ERA-15

A global heat and fresh water dataset based on the data of the second ECMWF Re-Analysis project (ERA-40) is presented that is constructed in the same way as the dataset based on the data of the first project (ERA-15) and can be used as surface boundary conditions for ocean models with sea ice components. The definition of these conditions is based on bulk formulae. A mean annual cycle on a daily basis was constructed from ERA-40 for all relevant parameters including wind stress. Continental runoff is considered by using a runoff model. To estimate implied meridional oceanic heat transports and to avoid temporal drifts of globally averaged deep ocean temperature and salinity in ocean model simulations, the heat and fresh water budgets have been closed by applying an inverse procedure to fine-tune the fluxes towards observed transports. Winds and short wave radiation at Southern higher latitudes and short and long wave radiation in the subsidence zones are corrected. Applied to any ocean/sea-ice model, the forcing dataset would induce only a relative small net sea-surface buoyancy loss. A comparison of both datasets shows that the effects of the changes in the assimilation system of ERA are larger than the effects due to the different periods. The latter effects reveal a southward shift of the Intertropical Convergence Zone (ITCZ) in time and a pattern in the difference of the net heat flux corresponding to a low phase of the North Atlantic Oscillation (NAO). This pattern is essentially determined by a similar pattern in the latent heat flux with a gradient across the North American basin of about 15 to 20 Wm-2 for the annual mean. That confirms that the first dataset is biased towards a NAO high phase whereas the second one covers a whole NAO period

An atlas of surface fluxes based on the ECMWF Re-Analysis- a climatological dataset to force global ocean general circulation models

A climatological dataset for forcing global ocean models has been derived from the Re-Analysis (ERA) of the European Centre for Medium-Range Weather Forecasts. This dataset has been constructed for an Ocean Model Intercomparison Project (OMIP), in which the Max-Planck-Institute for Meteorology (MPI), the German Climate Computing Center in Hamburg, and the Alfred Wegener Institute Foundation for Polar and Marine Research in Bremerhaven were involved. The dataset is referred to as \OMIP-Forcing". In OMIP, the focus was on the intercomparison of the mean global circulation simulated by different ocean models. Therefore, a mean annual cycle has been produced from the 15 years of ERA by using Gaussian filltering with daily fluctuations superimposed. The precipitation and evaporation over the continents have been transformed into runoff A scheme has been used which is based on the main drainage basins as well as the catchment areas and annual runoff observations of the 35 largest rivers. The scheme is run independently of the ocean models. The budgets of the heat and the fresh water uxes have been closed by modifying the bulk formulae. All three forecast cycles of ERA have been examined with respect to the demands for the closure procedure. The 24 hour cycle has the best properties. Therefore, this cycle has been chosen to be the base of the OMIP-Forcing. The dataset is compared to six other climatologies: the direct output of ERA, the Re-Analysis of the National Center for Environmental Prediction and the National Center for Atmosperic Research (NCEP/NCAR), the Comprehensive Ocean Atmosphere Data Sets (COADS) in three dierent versions (Oberhuber, da Silva, and the Southampton Oceanographic Centre), and the output of the atmospheric model ECHAM4 of the MPI