11β-HSD2 SUMOylation Modulates Cortisol-induced Mineralocorticoid Receptor Nuclear Translocation Independently of Effects on Transactivation

The enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) has an essential role in aldosterone target tissues, conferring aldosterone selectivity for the mineralocorticoid receptor (MR) by converting 11β-hydroxyglucocorticoids to inactive 11-ketosteroids. Congenital deficiency of 11β-HSD2 causes a form of salt-sensitive hypertension known as the syndrome of apparent mineralocorticoid excess. The disease phenotype, which ranges from mild to severe, correlates well with reduction in enzyme activity. Furthermore, polymorphisms in the 11β-HSD2 coding gene (HSD11B2) have been linked to high blood pressure and salt sensitivity, major cardiovascular risk factors. 11β-HSD2 expression is controlled by different factors such as cytokines, sex steroids, or vasopressin, but posttranslational modulation of its activity has not been explored. Analysis of 11β-HSD2 sequence revealed a consensus site for conjugation of small ubiquitin-related modifier (SUMO) peptide, a major posttranslational regulatory event in several cellular processes. Our results demonstrate that 11β-HSD2 is SUMOylated at lysine 266. Non-SUMOylatable mutant K266R showed slightly higher substrate affinity and decreased Vmax, but no effects on protein stability or subcellular localization. Despite mild changes in enzyme activity, mutant K266R was unable to prevent cortisol-dependent MR nuclear translocation. The same effect was achieved by coexpression of wild-type 11β-HSD2 with sentrin-specific protease 1, a protease that catalyzes SUMO deconjugation. In the presence of 11β-HSD2-K266R, increased nuclear MR localization did not correlate with increased response to cortisol or increased recruitment of transcriptional coregulators. Taken together, our data suggests that SUMOylation of 11β-HSD2 at residue K266 modulates cortisol-mediated MR nuclear translocation independently of effects on transactivation

Telomere Roles in Fungal Genome Evolution and Adaptation

Telomeres form the ends of linear chromosomes and usually comprise protein complexes that bind to simple repeated sequence motifs that are added to the 3′ ends of DNA by the telomerase reverse transcriptase (TERT). One of the primary functions attributed to telomeres is to solve the “end-replication problem” which, if left unaddressed, would cause gradual, inexorable attrition of sequences from the chromosome ends and, eventually, loss of viability. Telomere-binding proteins also protect the chromosome from 5′ to 3′ exonuclease action, and disguise the chromosome ends from the double-strand break repair machinery whose illegitimate action potentially generates catastrophic chromosome aberrations. Telomeres are of special interest in the blast fungus, Pyricularia, because the adjacent regions are enriched in genes controlling interactions with host plants, and the chromosome ends show enhanced polymorphism and genetic instability. Previously, we showed that telomere instability in some P. oryzae strains is caused by novel retrotransposons (MoTeRs) that insert in telomere repeats, generating interstitial telomere sequences that drive frequent, break-induced rearrangements. Here, we sought to gain further insight on telomeric involvement in shaping Pyricularia genome architecture by characterizing sequence polymorphisms at chromosome ends, and surrounding internalized MoTeR loci (relics) and interstitial telomere repeats. This provided evidence that telomere dynamics have played historical, and likely ongoing, roles in shaping the Pyricularia genome. We further demonstrate that even telomeres lacking MoTeR insertions are poorly preserved, such that the telomere-adjacent sequences exhibit frequent presence/absence polymorphism, as well as exchanges with the genome interior. Using TERT knockout experiments, we characterized chromosomal responses to failed telomere maintenance which suggested that much of the MoTeR relic-/interstitial telomere-associated polymorphism could be driven by compromised telomere function. Finally, we describe three possible examples of a phenomenon known as “Adaptive Telomere Failure,” where spontaneous losses of telomere maintenance drive rapid accumulation of sequence polymorphism with possible adaptive advantages. Together, our data suggest that telomere maintenance is frequently compromised in Pyricularia but the chromosome alterations resulting from telomere failure are not as catastrophic as prior research would predict, and may, in fact, be potent drivers of adaptive polymorphism

An ocean-colour time series for use in climate studies: the experience of the ocean-colour climate change initiate (OC-CCI)

Ocean colour is recognised as an Essential Climate Variable (ECV) by the Global Climate Observing System (GCOS); and spectrally-resolved water-leaving radiances (or remote-sensing reflectances) in the visible domain, and chlorophyll-a concentration are identified as required ECV products. Time series of the products at the global scale and at high spatial resolution, derived from ocean-colour data, are key to studying the dynamics of phytoplankton at seasonal and inter-annual scales; their role in marine biogeochemistry; the global carbon cycle; the modulation of how phytoplankton distribute solar-induced heat in the upper layers of the ocean; and the response of the marine ecosystem to climate variability and change. However, generating a long time series of these products from ocean colour data is not a trivial task: algorithms that are best suited for climate studies have to be selected from a number that are available for atmospheric correction of the satellite signal and for retrieval of chlorophyll-a concentration; since satellites have a finite life span, data from multiple sensors have to be merged to create a single time series, and any uncorrected inter-sensor biases could introduce artefacts in the series, e.g., different sensors monitor radiances at different wavebands such that producing a consistent time series of reflectances is not straightforward. Another requirement is that the products have to be validated against in situ observations. Furthermore, the uncertainties in the products have to be quantified, ideally on a pixel-by-pixel basis, to facilitate applications and interpretations that are consistent with the quality of the data. This paper outlines an approach that was adopted for generating an ocean-colour time series for climate studies, using data from the MERIS (MEdium spectral Resolution Imaging Spectrometer) sensor of the European Space Agency; the SeaWiFS (Sea viewingWide-Field-of-view Sensor) and MODIS-Aqua (Moderate-resolution Imaging Spectroradiometer-Aqua) sensors from the National Aeronautics and Space Administration (USA); and VIIRS (Visible and Infrared Imaging Radiometer Suite) from the National Oceanic and Atmospheric Administration (USA). The time series now covers the period from late 1997 to end of 2018. To ensure that the products meet, as well as possible, the requirements of the user community, marine-ecosystem modellers, and remote-sensing scientists were consulted at the outset on their immediate and longer-term requirements as well as on their expectations of ocean-colour data for use in climate research. Taking the user requirements into account, a series of objective criteria were established, against which available algorithms for processing ocean-colour data were evaluated and ranked. The algorithms that performed best with respect to the climate user requirements were selected to process data from the satellite sensors. Remote-sensing reflectance data from MODIS-Aqua, MERIS, and VIIRS were band-shifted to match the wavebands of SeaWiFS. Overlapping data were used to correct for mean biases between sensors at every pixel. The remote-sensing reflectance data derived from the sensors were merged, and the selected in-water algorithm was applied to the merged data to generate maps of chlorophyll concentration, inherent optical properties at SeaWiFS wavelengths, and the diffuse attenuation coefficient at 490 nm. The merged products were validated against in situ observations. The uncertainties established on the basis of comparisons with in situ data were combined with an optical classification of the remote-sensing reflectance data using a fuzzy-logic approach, and were used to generate uncertainties (root mean square difference and bias) for each product at each pixel

Comparative genome structure, secondary metabolite, and effector coding capacity across Cochliobolus pathogens.

The genomes of five Cochliobolus heterostrophus strains, two Cochliobolus sativus strains, three additional Cochliobolus species (Cochliobolus victoriae, Cochliobolus carbonum, Cochliobolus miyabeanus), and closely related Setosphaeria turcica were sequenced at the Joint Genome Institute (JGI). The datasets were used to identify SNPs between strains and species, unique genomic regions, core secondary metabolism genes, and small secreted protein (SSP) candidate effector encoding genes with a view towards pinpointing structural elements and gene content associated with specificity of these closely related fungi to different cereal hosts. Whole-genome alignment shows that three to five percent of each genome differs between strains of the same species, while a quarter of each genome differs between species. On average, SNP counts among field isolates of the same C. heterostrophus species are more than 25× higher than those between inbred lines and 50× lower than SNPs between Cochliobolus species. The suites of nonribosomal peptide synthetase (NRPS), polyketide synthase (PKS), and SSP-encoding genes are astoundingly diverse among species but remarkably conserved among isolates of the same species, whether inbred or field strains, except for defining examples that map to unique genomic regions. Functional analysis of several strain-unique PKSs and NRPSs reveal a strong correlation with a role in virulence

BLAST redundancy cleaner: a bioinformatics tool that allows for easy viewing of complex genomic repeat BLAST results

Most presently characterized genomic repeat elements contain internal repeat sequences, causing bioinformatics program like BLAST to return redundant hits. To combat this problem, we have developed BLASTrec: a command-line tool implemented in Python v3+ that can flexibly clean BLAST reports to remove redundancy. Results are returned in in file formats that allow for easy and compact viewing in visualizers such as IGV. BLASTrec tool supports an assortment of options that control the cleanliness of the final output, final output filetypes, and provide the ability to run BLASTn-short in addition to BLASTn. Furthermore, BLASTrec can be used in a wide variety of genomic studies, including characterizing the movement of known genomic repeat elements and identifying potential novel repeat elements through genome self-comparison. This works is a part of the NSF project to investigate telomere roles in fungal genome evolution: Dr. Mark Farman (PI)

Association between findings on palmarodorsal radiographic images and detection of a fracture in the proximal sesamoid bones of forelimbs obtained from cadavers of racing Thoroughbreds

abstract: Objective: Sample Population: Procedure: Results: Conclusions and Clinical Relevance: To determine the distribution for limbs and bones in horses with fractures of the proximal sesamoid bones and relationships with findings on palmarodorsal radiographic images.Proximal sesamoid bones obtained from both forelimbs of cadavers of 328 racing Thoroughbreds.Osteophytes; large vascular channels; and fracture location, orientation, configuration, and margin distinctness were categorized by use of high-detail contact palmarodorsal radiographs. Distributions of findings were determined. Relationships between radiographic findings and fracture characteristics were examined by use of chi2 and logistic regression techniques.Fractures were detected in 136 (41.5%) horses. Biaxial fractures were evident in 109 (80%) horses with a fracture. Osteophytes and large vascular channels were evident in 266 (81%) and 325 (99%) horses, respectively. Medial bones typically had complete transverse or split transverse simple fractures, indistinct fracture margins, > 1 vascular channel that was > 1 mm in width, and osteophytes in abaxial wing and basilar middle or basilar abaxial locations. Lateral bones typically had an oblique fracture and distinct fracture margins. Odds of proximal sesamoid bone fracture were approximately 2 to 5 times higher in bones without radiographic evidence of osteophytes or large vascular channels, respectively.Biaxial fractures of proximal sesamoid bones were common in cadavers of racing Thoroughbreds. Differences between medial and lateral bones for characteristics associated with fracture may relate to differences in fracture pathogeneses for these bones. Osteophytes and vascular channels were common findings; however, fractures were less likely to occur in bones with these features