Preferential binding to elk-1 by sle-associated il10 risk allele upregulates il10 expression

Immunoregulatory cytokine interleukin-10 (IL-10) is elevated in sera from patients with systemic lupus erythematosus (SLE) correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s) and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported IL10 variant, rs3024505 located at 1 kb downstream of IL10, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA) (P = 2.7×10−8, OR = 1.30), but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10, respectively), and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G) allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating IL10 expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1) detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the IL10 rs3122605-G allele upregulates IL10 expression and confers increased risk for SLE in European Americans.

Long-term depression activates transcription of immediate early transcription factor genes: involvement of serum response factor/Elk-1

Long-term depression (LTD) is one of the paradigms used in vivo or ex vivo for studying memory formation. In order to identify genes with potential relevance for memory formation we used mouse organotypic hippocampal slice cultures in which chemical LTD was induced by applications of 3,5-dihydroxyphenylglycine (DHPG). The induction of chemical LTD was robust, as monitored electrophysiologically. Gene expression analysis after chemical LTD induction was performed using cDNA microarrays containing >7,000 probes. The DHPG-induced expression of immediate early genes (c-fos, junB, egr1 and nr4a1) was subsequently verified by TaqMan polymerase chain reaction. Bioinformatic analysis suggested a common regulator element [serum response factor (SRF)/Elk-1 binding sites] within the promoter region of these genes. Indeed, here we could show a DHPG-dependent binding of SRF at the SRF response element (SRE) site within the promoter region of c-fos and junB. However, SRF binding to egr1 promoter sites was constitutive. The phosphorylation of the ternary complex factor Elk-1 and its localization in the nucleus of hippocampal neurones after DHPG treatment was shown by immunofluorescence using a phosphospecific antibody. We suggest that LTD leads to SRF/Elk-1-regulated gene expression of immediate early transcription factors, which could in turn promote a second broader wave of gene expression.

The role of the seed coat in phytochrome-controlled seed germination in Lactuca sativa L. cv. Grand Rapids

The effect of scarification with sodium hypochloride on light sensitivity in seeds of Lactuca sativa L. cv. Grand Rapids is presented in the paper. Light-requiring lettuce seeds germinated in both dark and continuous light after scarification and 36 degrees C pre-incubation restored light sensitivity at 25 degrees C. Curves of dose-response indicated that chemical scarification induced a change in the control of seed germination from Low Fluence Response to the Very Low Fluence Response. Pre-incubation at 36 degrees C return the control to the Low Fluence Response of phytochrome action.

Comparison of Gross Pathology, Histopathology, and Mycobacterial Culture for the Diagnosis of Tuberculosis in Elk (Cervus elaphus)

Using the isolation of Mycobacterium bovis as the reference standard, this study evaluated the sensitivity, specificity and kappa statistic of gross pathology (abattoir postmortem inspection), histopathology, and parallel or series combinations of the two for the diagnosis of tuberculosis in 430 elk and red deer. Two histopathology interpretations were evaluated: histopathology I, where the presence of lesions compatible with tuberculosis was considered positive, and histopathology II, where lesions compatible with tuberculosis or a select group of additional possible diagnoses were considered positive. In the 73 animals from which M. bovis was isolated, gross lesions of tuberculosis were most often in the lung (48), the retropharyngeal lymph nodes (36), the mesenteric lymph nodes (35), and the mediastinal lymph nodes (16). Other mycobacterial isolates included: 11 M. paratuberculosis, 11 M. avium, and 28 rapidly growing species or M. terrae complex. The sensitivity estimates of gross pathology and histopathology I were 93% (95% confidence limits [CL] 84,97%) and 88% [CL 77,94%], respectively, and the specificity of both was 89% [CL 85,92%]). The sensitivity and specificity of histopathology II were 89% (CL 79,95%) and 77% (CL 72,81%), respectively. The highest sensitivity estimates (93- 95% [CL 84,98%]) were obtained by interpreting gross pathology and histopathology in parallel (where an animal had to be positive on at least one of the two, to be classified as combination positive). The highest specificity estimates (94-95% [CL 91-97%]) were generated when the two tests were interpreted in series (an animal had to be positive on both tests to be classified as combination positive). The presence of gross or microscopic lesions showed moderate to good agreement with the isolation of M. bovis (Kappa = 65-69%). The results show that post-mortem inspection, histopathology and culture do not necessarily recognize the same infected animals and that the spectra of animals identified by the tests overlaps.

Simulation of Ground-Water Flow in the Cedar River Alluvial Aquifer Flow System, Cedar Rapids, Iowa Scientific

The Cedar River alluvial aquifer is the primary source of municipal water in the Cedar Rapids, Iowa, area. Since 1992, the U.S. Geological Survey, in cooperation with the City of Cedar Rapids, has investigated the hydrogeology and water quality of the Cedar River alluvial aquifer. This report describes a detailed analysis of the ground-water flow system in the alluvial aquifer, particularly near well field areas. The ground-water flow system in the Cedar Rapids area consists of two main components, the unconsolidated Quaternary deposits and the underlying carbonate bedrock that has a variable fracture density. Quaternary deposits consist of eolian sand, loess, alluvium, and glacial till. Devonian and Silurian bedrock aquifers overlie the Maquoketa Shale (Formation) of Ordovician age, a regional confining unit. Ground-water and surface-water data were collected during the study to better define the hydrogeology of the Cedar River alluvial aquifer and Devonian and Silurian aquifers. Stream stage and discharge, ground-water levels, and estimates of aquifer hydraulic properties were used to develop a conceptual ground-water flow model and to construct and calibrate a model of the flow system. This model was used to quantify the movement of water between the various components of the alluvial aquifer flow system and provide an improved understanding of the hydrology of the alluvial aquifer.

Increased Risk of Chronic Wasting Disease in Rocky Mountain Elk Associated With Decreased Magnesium and Increased Manganese in Brain Tissue

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of Rocky Mountain elk in North America. Recent studies suggest that tissue and blood mineral levels may be valuable in assessing TSE infection in sheep and cattle. The objectives of this study were to examine baseline levels of copper, manganese, magnesium, zinc, selenium, and molybdenum in the brains of Rocky Mountain elk with differing prion genotypes and to assess the association of mineral levels with CWD infection. Elk with leucine at prion position 132 had significantly lower magnesium levels than elk with 2 copies of methionine. Chronic wasting disease-positive elk had significantly lower magnesium than control elk. The incorporation of manganese levels in addition to magnesium significantly refined explanatory ability, even though manganese alone was not significantly associated with CWD. This study demonstrated that mineral analysis may provide an additional disease correlate for assessing CWD risk, particularly in conjunction with genotype.

Elk in Nebraska: Opportunity or Another Private-Public Land Conundrum

We conducted a comprehensive research project on elk in the Pine Ridge region of northwestern Nebraska from 1995 to 2002 to determine ecological factors that could be used to improve management and reduce damage. The population ranged from 120 to 150 animals, with an average calf:cow ratio of 0.5:1 and bull:cow ratio of 0.4:1. We located 21 radio-collared female elk 6,311 times during 1995 to 1997. Seasonal home ranges of 2 herds were 10 and 44 km2, while average annual home ranges of the herds were much larger (483 and 440 km2, respectively). All wintering areas (n = 21) and 80% of the calving areas (n = 22) were located on privately-owned land. Active timber harvest temporarily displaced elk, most notably during the calving season. Elk shifted home ranges in association with the seasonal availability of agricultural crops, in particular, alfalfa, oats, and winter wheat. Population models indicated that static levels of hunting mortality would lead to a stable population of about 130 elk over 10 years. Most landowners in the Pine Ridge (57%) favored free-ranging elk, but 26% were concerned about damage to agricultural crops and competition with livestock. Habitat suitability models and estimates of social carrying capacity indicate that up to 600 elk could be sustained in the Pine Ridge without significant impacts to landowners. We recommended an integrated management program used to enhance elk habitat on publicly-owned land and redistribute elk from privately-owned land.

La lingua e l'estraneità: Franco Biondi e la letteratura dell'immigrazione in Germania. Proposta di traduzione di "Und nun schieben sie mich ab"

In questo lavoro è presentata una proposta di traduzione del racconto Und nun schieben sie mich ab (Biondi, 1985: 168- 174), di Franco Biondi, un autore di origini italiane residente in Germania dal 1965 (Amodeo, 2007: 6). Data la sua biografia, Biondi è un autore emblematico tanto della letteratura italiana della migrazione, quanto della letteratura dell’immigrazione in Germania, a testimonianza di come questa letteratura sia riuscita a superare i confini letterari nazionali per entrare a far parte di una «letteratura mondiale della transculturalità» (Amodeo, 2000: 327) . Considerati il terreno comune su cui si sono sviluppate le opere di autori di varie nazionalità in Germania, e l’eterogeneità dei contesti letterari e sociali degli autori italiani nei vari Paesi, si è ritenuto più efficace focalizzare i capitoli teorici del lavoro sulla letteratura dell’immigrazione in Germania, con un’attenzione particolare agli autori di origine italiana. La proposta di traduzione sarà preceduta da un inquadramento storico degli albori della letteratura dell’immigrazione in Germania, nata negli anni Sessanta del Novecento. Da lì si procederà presentando gli sviluppi di questa letteratura fino agli anni più recenti: si partirà dalla letteratura dell’immigrazione in Germania prodotta da autori di varie nazionalità, entrando poi nel merito degli autori di origine italiana attivi in Germania. Il terzo capitolo è dedicato a Franco Biondi, di cui saranno presentate una breve biografia e le opere più significative. Il quarto e il quinto capitolo sono dedicati interamente al racconto Und nun schieben sie mich ab (Biondi, 1985): in particolare, il quarto capitolo contiene un’analisi del tema e del contenuto del racconto, contestualizzato poi all’interno della raccolta “Passavantis Rückkehr” (Ibid.) e dell’opera dell’autore; in questo capitolo inoltre viene presentata un’analisi linguistica e stilistica del racconto. Il quinto capitolo contiene la proposta di traduzione, seguita da un commento della traduzione e delle strategie utilizzate.