Surficial Geology of the Des Moines Lobe of Iowa Hancock, Kossuth, Winnebago and Wright Counties

https://ir.uiowa.edu/igs_ofm/1019/thumbnail.jp

Specific oligomerization of the 5-HT1A receptor in the plasma membrane

In the present study we analyze the oligomerization of the 5-HT1A receptor within living cells at the sub-cellular level. Using a 2-excitation Förster Resonance Energy Transfer (FRET) method combined with spectral microscopy we are able to estimate the efficiency of energy transfer based on donor quenching as well as acceptor sensitization between CFP-and YFP-tagged 5-HT1A receptors at the plasma membrane. Through the analysis of the level of apparent FRET efficiency over the various relative amounts of donor and acceptor, as well as over a range of total surface expressions of the receptor, we verify the specific interaction of these receptors. Furthermore we study the role of acylation in this interaction through measurements of a palmitoylation-deficient 5-HT1A receptor mutant. Palmitoylation increases the tendency of a receptor to localize in lipid rich microdomains of the plasma membrane. This increases the effective surface density of the receptor and provides for a higher level of stochastic interaction

Dynamically and Statistically Downscaled Seasonal Simulations of Maximum Surface Air Temperature Over the Southeastern United States

Coarsely resolved surface air temperature (2 m height) seasonal integrations from the Florida State University/Center for Ocean-Atmospheric Prediction Studies Global Spectral Model (FSU/COAPS GSM) (~1.8º lon.-lat. (T63)) for the period of 1994 to 2002 (March through September each year) are downscaled to a fine spatial scale of ~20 km. Dynamical and statistical downscaling methods are applied for the southeastern United States region, covering Florida, Georgia, and Alabama. Dynamical downscaling is conducted by running the FSU/COAPS Nested Regional Spectral Model (NRSM), which is nested into the domain of the FSU/COAPS GSM. We additionally present a new statistical downscaling method. The rationale for the statistical approach is that clearer separation of prominent climate signals (e.g., seasonal cycle, intraseasonal, or interannual oscillations) in observation and GSM, respectively, over the training period can facilitate the identification of the statistical relationship in climate variability between two data sets. Cyclostationary Empirical Orthogonal Function (CSEOF) analysis and multiple regressions are trained with those data sets to extract their statistical relationship, which eventually leads to better prediction of regional climate from the large-scale simulations. Downscaled temperatures are compared with the FSU/COAPS GSM fields and observations. Downscaled seasonal anomalies exhibit strong agreement with observations and a reduction in bias relative to the direct GSM simulations. Interannual temperature change is also reasonably simulated at local grid points. A series of evaluations including mean absolute errors, anomaly correlations, frequency of extreme events, and categorical predictability reveal that both downscaling techniques can be reliably used for numerous seasonal climate applications

Cytokines and Inflammatory Mediators [30-39]: 30. The LPS Stimulated Production of Interleukin-10 is not Associated with -819C/T and -592C/A Promoter Polymorphisms in Healthy Indian Subjects

Background: Interleukin-10 is a pivotal immunoregulatory cytokine with pleiotropic effects on the immune system. IL-10 promoter polymorphisms have been associated with disease susceptibility and the ability to secrete IL-10 in vitro. We suspected that the association of the widely studied -819C/T and -592C/A polymorphisms with the IL-10 production might vary between ethnic groups. Therefore, we examined the association of -819 C/T and -592 C/A promoter polymorphisms with in vitro LPS stimulated secretion of IL-10 in normal healthy Indian volunteers. Methods: Peripheral blood was collected from 103 healthy volunteers and diluted whole blood cultures were set up with 100 ng/ml of LPS as stimulant: supernatant was collected at 24 h and IL-10 levels were assayed by ELISA. Genotyping was done for -819C/T polymorphism in 101 individuals and -592C/A polymorphism in 68 individuals by polymerase chain reaction followed by RFLP. The differences in IL-10 production between the genotypes were analysed by ANOVA. Results: There were 30, 47 and 24 individuals with the CC, CT and TT genotypes with a minor allele (T) frequency of 47% for the -819C/T polymorphism. The CC and TT genotypes at position -819 were strongly associated with CC and AA genotypes at -592 position suggestive of strong linkage disequilibrium. There was no association between the -819 genotype and the in vitro LPS stimulated IL-10 levels. Conclusions: The -819C/T and the -592 C/A polymorphisms of the IL-10 promoter region are not significantly associated with LPS stimulated IL-10 production healthy Indian subjects. Disclosure statement: All authors have declared no conflicts of interes

Phytophthora Have Distinct Endogenous Small RNA Populations That Include Short Interfering and microRNAs

In eukaryotes, RNA silencing pathways utilize 20-30-nucleotide small RNAs to regulate gene expression, specify and maintain chromatin structure, and repress viruses and mobile genetic elements. RNA silencing was likely present in the common ancestor of modern eukaryotes, but most research has focused on plant and animal RNA silencing systems. Phytophthora species belong to a phylogenetically distinct group of economically important plant pathogens that cause billions of dollars in yield losses annually as well as ecologically devastating outbreaks. We analyzed the small RNA-generating components of the genomes of P. infestans, P. sojae and P. ramorum using bioinformatics, genetic, phylogenetic and high-throughput sequencing-based methods. Each species produces two distinct populations of small RNAs that are predominantly 21- or 25-nucleotides long. The 25-nucleotide small RNAs were primarily derived from loci encoding transposable elements and we propose that these small RNAs define a pathway of short-interfering RNAs that silence repetitive genetic elements. The 21-nucleotide small RNAs were primarily derived from inverted repeats, including a novel microRNA family that is conserved among the three species, and several gene families, including Crinkler effectors and type III fibronectins. The Phytophthora microRNA is predicted to target a family of amino acid/auxin permeases, and we propose that 21-nucleotide small RNAs function at the post-transcriptional level. The functional significance of microRNA-guided regulation of amino acid/auxin permeases and the association of 21-nucleotide small RNAs with Crinkler effectors remains unclear, but this work provides a framework for testing the role of small RNAs in Phytophthora biology and pathogenesis in future work

Serotonylation of Vascular Proteins Important to Contraction

BACKGROUND:Serotonin (5-hydroxytryptamine, 5-HT) was named for its source (sero-) and ability to modify smooth muscle tone (tonin). The biological effects of 5-HT are believed to be carried out by stimulation of serotonin receptors at the plasma membrane. Serotonin has recently been shown to be synthesized in vascular smooth muscle and taken up from external sources, placing 5-HT inside the cell. The enzyme transglutaminase uses primary amines such as 5-HT to covalently modify proteins on glutamine residues. We tested the hypothesis that 5-HT is a substrate for transglutaminase in arterial vascular smooth muscle, with protein serotonylation having physiological function. METHODOLOGY/PRINCIPAL FINDINGS:The model was the rat aorta and cultured aortic smooth muscle cells. Western analysis demonstrated that transglutaminase II was present in vascular tissue, and transglutaminase activity was observed as a cystamine-inhibitable incorporation of the free amine pentylamine-biotin into arterial proteins. Serotonin-biotin was incorporated into alpha-actin, beta-actin, gamma-actin, myosin heavy chain and filamin A as shown through tandem mass spectrometry. Using antibodies directed against biotin or 5-HT, immunoprecipitation and immunocytochemistry confirmed serotonylation of smooth muscle alpha-actin. Importantly, the alpha-actin-dependent process of arterial isometric contraction to 5-HT was reduced by cystamine. CONCLUSIONS:5-HT covalently modifies proteins integral to contractility and the cytoskeleton. These findings suggest new mechanisms of action for 5-HT in vascular smooth muscle and consideration for intracellular effects of primary amines

Common Features at the Start of the Neurodegeneration Cascade

A single-molecule study reveals that neurotoxic proteins share common structural features that may trigger neurodegeneration, thus identifying new targets for therapy and diagnosis

FungalRV: adhesin prediction and immunoinformatics portal for human fungal pathogens

<p>Abstract</p> <p>Background</p> <p>The availability of sequence data of human pathogenic fungi generates opportunities to develop Bioinformatics tools and resources for vaccine development towards benefitting at-risk patients.</p> <p>Description</p> <p>We have developed a fungal adhesin predictor and an immunoinformatics database with predicted adhesins. Based on literature search and domain analysis, we prepared a positive dataset comprising adhesin protein sequences from human fungal pathogens <it>Candida albicans, Candida glabrata, Aspergillus fumigatus, Coccidioides immitis, Coccidioides posadasii, Histoplasma capsulatum, Blastomyces dermatitidis, Pneumocystis carinii, Pneumocystis jirovecii and Paracoccidioides brasiliensis</it>. The negative dataset consisted of proteins with high probability to function intracellularly. We have used 3945 compositional properties including frequencies of mono, doublet, triplet, and multiplets of amino acids and hydrophobic properties as input features of protein sequences to Support Vector Machine. Best classifiers were identified through an exhaustive search of 588 parameters and meeting the criteria of best Mathews Correlation Coefficient and lowest coefficient of variation among the 3 fold cross validation datasets. The "FungalRV adhesin predictor" was built on three models whose average Mathews Correlation Coefficient was in the range 0.89-0.90 and its coefficient of variation across three fold cross validation datasets in the range 1.2% - 2.74% at threshold score of 0. We obtained an overall MCC value of 0.8702 considering all 8 pathogens, namely, <it>C. albicans, C. glabrata, A. fumigatus, B. dermatitidis, C. immitis, C. posadasii, H. capsulatum </it>and <it>P. brasiliensis </it>thus showing high sensitivity and specificity at a threshold of 0.511. In case of <it>P. brasiliensis </it>the algorithm achieved a sensitivity of 66.67%. A total of 307 fungal adhesins and adhesin like proteins were predicted from the entire proteomes of eight human pathogenic fungal species. The immunoinformatics analysis data on these proteins were organized for easy user interface analysis. A Web interface was developed for analysis by users. The predicted adhesin sequences were processed through 18 immunoinformatics algorithms and these data have been organized into MySQL backend. A user friendly interface has been developed for experimental researchers for retrieving information from the database.</p> <p>Conclusion</p> <p>FungalRV webserver facilitating the discovery process for novel human pathogenic fungal adhesin vaccine has been developed.</p