Phosphorylation modulates FOXC2 transcriptional program by controlling the high-order interaction with DNA.

Phosphorylation of transcription factors is a rapid and reversible process linking cell signaling and control of gene expression, therefore understanding how it controls the transcription factor functions is one of the challenges of functional genomics. We performed such analysis for the forkhead transcription factor FOXC2 mutated in human hereditary disease lymphedemadistichiasis and important for the development of venous and lymphatic valves and lymphatic collecting vessels. We found that FOXC2 is phosphorylated in a cell-cycle dependent manner on eight evolutionary conserved serine/threonine residues, seven of which are clustered within a 70 amino acid domain. Surprisingly, the mutation of phosphorylation sites or a complete deletion of the domain did not affect the transcriptional activity of FOXC2 in a synthetic reporter assay. However, overexpression of the wild type or phosphorylation-deficient mutant resulted in overlapping but distinct gene expression profiles suggesting that binding of FOXC2 to individual sites under physiological conditions is affected by phosphorylation. To gain a direct insight into the role of FOXC2 phosphorylation, we performed comparative genome-wide location analysis (ChIP-chip) of wild type and phosphorylation-deficient FOXC2 in primary lymphatic endothelial cells. The effect of loss of phosphorylation on FOXC2 binding to genomic sites ranged from no effect to nearly complete inhibition of binding, suggesting a mechanism for how FOXC2 transcriptional program can be differentially regulated depending on FOXC2 phosphorylation status. Based on these results, we propose an extension to the enhanceosome model, where a network of genomic context-dependent DNA-protein and protein-protein interactions not only distinguishes a functional site from a nonphysiological site, but also determines whether binding to the functional site can be regulated by phosphorylation. Moreover, our results indicate that FOXC2 may have different roles in quiescent versus proliferating lymphatic endothelial cells in vivo.

Executive Order Number Twenty-One, February 1, 2010

Orders that the Executive Director of the Iowa Finance Authority, shall serve as the Governor’s designee related to the issuance of Qualified Midwestern Disaster Area Bonds.

Executive Order Number Twenty-Two, February 3, 2010

Requests all state departments and agencies to consider using Project Labor Agreements on large-scale construction projects to provide structure and stability, promote efficient, on-time completion and ensure the high standards and reasonable costs on the projects in order to move Iowa’s economy forward.

Executive Order Number Twenty-Three, April 9, 2010

Establishes specific steps to be taken by the executive branch to work in concert with the legislation in the effort to contain rising insurance costs as much as possible for all Iowans.

Executive Order Number Twenty-Four, May 28, 2010

Restructures the Office of the State Long-Term Care Ombudsman by mandating that the Office become institutionally independent by means of relocating to a separate physical space and directing the Ombudsman’s Office to propose legislation that will ensure the independence of the Office, as required under the federal Older Americans Act.

Report on a review of selected general and application controls over the Iowa State University of Science and Technology (Iowa State University) Purchase Order/Requisition System for the period of March 20 through April 28, 2009

Report on a review of selected general and application controls over the Iowa State University of Science and Technology (Iowa State University) Purchase Order/Requisition System for the period of March 20 through April 28, 2009

Crescent and star shapes of members of the Chlamydiales order: impact of fixative methods.

Members of the Chlamydiales order all share a biphasic lifecycle alternating between small infectious particles, the elementary bodies (EBs) and larger intracellular forms able to replicate, the reticulate bodies. Whereas the classical Chlamydia usually harbours round-shaped EBs, some members of the Chlamydia-related families display crescent and star-shaped morphologies by electron microscopy. To determine the impact of fixative methods on the shape of the bacterial cells, different buffer and fixative combinations were tested on purified EBs of Criblamydia sequanensis, Estrella lausannensis, Parachlamydia acanthamoebae, and Waddlia chondrophila. A linear discriminant analysis was performed on particle metrics extracted from electron microscopy images to recognize crescent, round, star and intermediary forms. Depending on the buffer and fixatives used, a mixture of alternative shapes were observed in varying proportions with stars and crescents being more frequent in C. sequanensis and P. acanthamoebae, respectively. No tested buffer and chemical fixative preserved ideally the round shape of a majority of bacteria and other methods such as deep-freezing and cryofixation should be applied. Although crescent and star shapes could represent a fixation artifact, they certainly point towards a diverse composition and organization of membrane proteins or intracellular structures rather than being a distinct developmental stage.

Executive Order Number Twenty-Five, August 6, 2010

July 24, 2010, the breach of the Lake Delhi dam caused flash floods and massive damage to persons and businesses and public infrastructure in Delaware and Jones counties and surrounding areas, including Jackson County, resulting in gubernatorial declarations of emergency and applications for federal disaster assistance for these areas.

Executive Order Number Twenty-Six, October 14, 2010

Iowa Efficiency Review Report identified 90 recommendations for improving the cost effectiveness and efficiency of delivering state government services.

Executive Order Number Twenty-Seven, November 29, 2010

Iowa Efficiency Review Report identified 90 recommendations for improving the cost effectiveness and efficiency of delivering state government services.

Executive Order Number Sixty Nine, January 14, 2011

The proliferation of Project Labor Agreements as a result of Executive Order Number 22, dated February 3, 2010, issued by Governor Chet Culver has impacted the essence and the spirit of the competitive bidding process for state funded projects and has infringed upon Iowa’s Right to Work law

Executive Order Number Seventy, January 14, 2011

The act of filing an application for restoration of the rights of citizenship is an important and necessary aspect of an offender’s process of reintegration into society.

Executive Order Number Seventy Two, April 4, 2011

The act adopting regulations to protect the health, safety and welfare of the people of the State of Iowa, state agencies should seek to achieve statutory goals as effectively and efficiently as possible without imposing unnecessary burdens that reduce jobs and hurt job growth

Adult native septic arthritis: 10 years in review in order to establish local guidelines on empiric antibiotic therapy.

Objective: Antibiotic stewardship includes development of practice guidelines incorporating local microbiology and resistance patterns. In case of septic arthritis (SA), addition of vancomycin to the empiric therapy and broad-spectrum antibiotherapy in some clinical settings are subjects of discussion. Our objective was to review the local epidemiology of native septic arthritis in adults, in order to establish local guidelines for empiric therapy. Methods: Retrospective study based on positive synovial fluid cultures and hospital discharge diagnoses of SA obtained from 1999 to 2008 in patients _16 years. Medical records were reviewed to assess the diagnosis and complete relevant clinical information. Results: During this ten-year period, we identified 233 SA on native joints in 231 patients. 107 episodes (46%) were obtained through positive synovial fluid cultures, and 126 episodes (54%) through the discharge diagnosis. 147 SA (63%) were large joint infections (LJI). 35 SA (15%) occurred in intravenous drug users. Preexisting arthropathy was present in 51% of cases. 42% of patients with small joint infection (SJI) were diabetic, vs. 23% with LJI (p = 0.003). When available, synovial fluid direct examination was positive in 35% of cases. Etiologic agents are reported in the table. Five of the 11 MRSA SA (45%) occurred in known carriers. SJI were more frequently polymicrobial (24% vs. 1%, p<0.001). For LJI, an empiric treatment with amoxicillin/clavulanate (A/C) would have been appropriate in 85% of cases. MRSA (8 cases) and tuberculous (7 cases) arthritis would have been the most frequently untreated pathogens. Addition of vancomycin to A/C in MRSA carriers would rise the adequacy to 87%. In contrast, A/C would cover only 75% of SJI (82% if restricted to non-diabetic patients). MRSA (3 cases) and P. aeruginosa (9 cases, 7 monomicrobial) would be the main untreated pathogens. An anti-pseudomonal penicillin would have been appropriate in 94% of cases of SJI (P = 0.002 vs. A/C, p = 0.19 if diabetic patients not included). Conclusions: Treatment with A/C seems adequate for empiric coverage of LJI in our setting. Broad-spectrum antibiotherapy was significantly superior for SJI in diabetic patients, due to different causative bacteria. In an area of low MRSA incidence, our results do not justify a systematic empiric therapy for MRSA, which should be considered in a known carrier.