Health consultation : Hills, Iowa perchlorate groundwater contamination site, Hills, Johnson County, EPA facility ID: IAN 000704368 (2004)

The U. S. Environmental Protection Agency (EPA) Region 7, as well as concerned citizens, asked the Iowa Department of Public Health (IDPH) Hazardous Waste Site Health Assessment Program to perform a health consultation for the Hills, Iowa Perchlorate Groundwater Contamination Site. Specifically, IDPH was asked to determine if EPA’s action of providing bottled water to residents whose private wells had concentrations of greater than 18 μg/L (micrograms per liter) or 18 parts per billion (ppb) perchlorate is protective of public health, and to address some community health concerns. The information included in this health consultation was current at the time of writing. Data that emerges later could alter this document’s conclusions and recommendations.

Identification of in vitro phosphorylation sites in the growth cone protein SCG10. Effect Of phosphorylation site mutants on microtubule-destabilizing activity.

SCG10 is a neuron-specific, membrane-associated protein that is highly concentrated in growth cones of developing neurons. Previous studies have suggested that it is a regulator of microtubule dynamics and that it may influence microtubule polymerization in growth cones. Here, we demonstrate that in vivo, SCG10 exists in both phosphorylated and unphosphorylated forms. By two-dimensional gel electrophoresis, two phosphoisoforms were detected in neonatal rat brain. Using in vitro phosphorylated recombinant protein, four phosphorylation sites were identified in the SCG10 sequence. Ser-50 and Ser-97 were the target sites for protein kinase A, Ser-62 and Ser-73 for mitogen-activated protein kinase and Ser-73 for cyclin-dependent kinase. We also show that overexpression of SCG10 induces a disruption of the microtubule network in COS-7 cells. By expressing different phosphorylation site mutants, we have dissected the roles of the individual phosphorylation sites in regulating its microtubule-destabilizing activity. We show that nonphosphorylatable mutants have increased activity, whereas mutants in which phosphorylation is mimicked by serine-to-aspartate substitutions have decreased activity. These data suggest that the microtubule-destabilizing activity of SCG10 is regulated by phosphorylation, and that SCG10 may link signal transduction of growth or guidance cues involving serine/threonine protein kinases to alterations of microtubule dynamics in the growth cone.

Effect of thinning on stem form and wood characteristics of teak (Tectona grandis) in a humid tropical site in Costa Rica

Abstract

dKDM5/LID regulates H3K4me3 dynamics at the transcription-start site (TSS) of actively transcribed developmental genes

H3K4me3 is a histone modification that accumulates at the transcription-start site (TSS) of active genes and is known to be important for transcription activation. The way in which H3K4me3 is regulated at TSS and the actual molecular basis of its contribution to transcription remain largely unanswered. To address these questions, we have analyzed the contribution of dKDM5/LID, the main H3K4me3 demethylase in Drosophila, to the regulation of the pattern of H3K4me3. ChIP-seq results show that, at developmental genes, dKDM5/LID localizes at TSS and regulates H3K4me3. dKDM5/LID target genes are highly transcribed and enriched in active RNApol II and H3K36me3, suggesting a positive contribution to transcription. Expression-profiling show that, though weakly, dKDM5/LID target genes are significantly downregulated upon dKDM5/LID depletion. Furthermore, dKDM5/LID depletion results in decreased RNApol II occupancy, particularly by the promoter-proximal Pol lloser5 form. Our results also show that ASH2, an evolutionarily conserved factor that locates at TSS and is required for H3K4me3, binds and positively regulates dKDM5/LID target genes. However, dKDM5/LID and ASH2 do not bind simultaneously and recognize different chromatin states, enriched in H3K4me3 and not, respectively. These results indicate that, at developmental genes, dKDM5/LID and ASH2 coordinately regulate H3K4me3 at TSS and that this dynamic regulation contributes to transcription.

Evaluating spine micro-architectural texture (via TBS) discriminates major osteoporotic fractures from controls both as well as and independent of site matched BMD: the Eastern European TBS study.

The aim of the study was to assess the clinical performance of the model combining areal bone mineral density (aBMD) at spine and microarchitecural texture (TBS) for the detection of the osteoporotic fracture. The Eastern European Study is a multicenter study (Serbia, Bulgaria, Romania and Ukraine) evaluating the role of TBS in routine clinical practice as a complement to aBMD. All scans were acquired on Hologic Discovery and GE Prodigy densitometers in a routine clinical manner. The additional clinical values of aBMD and TBS were analyzed using a two steps classification tree approach (aBMD followed by TBS tertiles) for all type of osteoporotic fracture (All-OP Fx). Sensitivity, specificity and accuracy of fracture detection as well as the Net Reclassification Index (NRI) were calculated. This study involves 1031 women subjects aged 45 and older recruited in east European countries. Clinical centers were cross-calibrated in terms of BMD and TBS. As expected, areal BMD (aBMD) at spine and TBS were only moderately correlated (r (2) = 0.19). Prevalence rate for All-OP Fx was 26 %. Subjects with fracture have significant lower TBS and aBMD than subjects without fracture (p < 0.01). TBS remains associated with the fracture even after adjustment for age and aBMD with an OR of 1.27 [1.07-1.51]. When using aBMD T-score of -2.5 and the lowest TBS tertile thresholds, both BMD and TBS were similar in terms of sensitivity (35 vs. 39 %), specificity (78 vs. 80 %) and accuracy (64 vs. 66 %). aBMD and TBS combination, induced a significant improvement in sensitivity (+28 %) and accuracy (+17 %) compared to aBMD alone whereas a moderate improvement was observed in terms of specificity (+9 %). The overall combination gain was 36 % as expressed using the NRI. aBMD and TBS combination decrease significantly the number of subjects needed to diagnose from 7 for aBMD alone to 2. In a multi-centre Eastern European cohort, we have shown that the use of TBS in addition to the aBMD permit to reclassified correctly more than one-third of the overall subjects. Furthermore, the number of subjects needed to diagnose fell to 2 subjects. Economical studies have to be performed to evaluate the gain induced by the use of TBS for the healthcare system.

Role of Toll-Like Receptor 9 Signaling in Experimental Leishmania braziliensis Infection.

Infection with Leishmania braziliensis causes cutaneous or mucocutaneous leismaniasis in humans. Toll-like receptor 9 (TLR9) expression has been found in granulomas of lesions in L. braziliensis-infected individuals. L. braziliensis inoculation in mice induces very small lesions that are self-healing, whereas deficiency in the TLR adaptor molecule, MyD88, renders mice susceptible to infection. The TLR involved has not been identified, prompting us to investigate if TLR9 triggering by the parasite contributes to the strong resistance to infection observed in L. braziliensis-inoculated mice. The parasites activated wild-type (WT) dendritic cells (DCs) in vitro but not DCs derived from TLR9(-/-) mice. TLR9(-/-) mice inoculated with L. braziliensis exhibited a transient susceptibility characterized by increased lesion size and parasite burden compared to those of WT mice. Surprisingly, elevated levels of gamma interferon (IFN-γ) were measured at the site of infection and in draining lymph node T cells of TLR9(-/-) mice at the peak of susceptibility, suggesting that unlike observations in vitro, the parasite could induce DC activation leading to the development of Th1 cells in the absence of TLR9 expression. Taken together, these data show that TLR9 signaling is important for the early control of lesion development and parasite burden but is dispensable for the differentiation of Th1 cells secreting IFN-γ, and the high levels of this cytokine are not sufficient to control early parasite replication following L. braziliensis infection.

Measures to prevent surgical site infections: what surgeons (should) do.

BACKGROUND: The present study was designed to evaluate surgeons' strategies and adherence to preventive measures against surgical site infections (SSIs). MATERIALS AND METHODS: All surgeons participating in a prospective Swiss multicentric surveillance program for SSIs received a questionnaire developed from the 2008 National (United Kingdom) Institute for Health and Clinical Excellence (NICE) clinical guidelines on prevention and treatment of SSIs. We focused on perioperative management and surgical technique in hernia surgery, cholecystectomy, appendectomy, and colon surgery (COL). RESULTS: Forty-five of 50 surgeons contacted (90%) responded. Smoking cessation and nutritional screening are regularly propagated by 1/3 and 1/2 of surgeons, respectively. Thirty-eight percent practice bowel preparation before COL. Preoperative hair removal is routinely (90%) performed in the operating room with electric clippers. About 50% administer antibiotic prophylaxis within 30 min before incision. Intra-abdominal drains are common after COL (43%). Two thirds of respondents apply nonocclusive wound dressings that are manipulated after hand disinfection (87%). Dressings are usually changed on postoperative day (POD) 2 (75%), and wounds remain undressed on POD 2-3 or 4-5 (36% each). CONCLUSIONS: Surgeons' strategies to prevent SSIs still differ widely. The adherence to the current NICE guidelines is low for many procedures regardless of the available level of evidence. Further research should provide convincing data in order to justify standardization of perioperative management.

Multispectral remote sensing for site-specific nitrogen fertilizer management

The objective of this work was to evaluate the use of multispectral remote sensing for site-specific nitrogen fertilizer management. Satellite imagery from the advanced spaceborne thermal emission and reflection radiometer (Aster) was acquired in a 23 ha corn-planted area in Iran. For the collection of field samples, a total of 53 pixels were selected by systematic randomized sampling. The total nitrogen content in corn leaf tissues in these pixels was evaluated. To predict corn canopy nitrogen content, different vegetation indices, such as normalized difference vegetation index (NDVI), soil-adjusted vegetation index (Savi), optimized soil-adjusted vegetation index (Osavi), modified chlorophyll absorption ratio index 2 (MCARI2), and modified triangle vegetation index 2 (MTVI2), were investigated. The supervised classification technique using the spectral angle mapper classifier (SAM) was performed to generate a nitrogen fertilization map. The MTVI2 presented the highest correlation (R²=0.87) and is a good predictor of corn canopy nitrogen content in the V13 stage, at 60 days after cultivating. Aster imagery can be used to predict nitrogen status in corn canopy. Classification results indicate three levels of required nitrogen per pixel: low (0-2.5 kg), medium (2.5-3 kg), and high (3-3.3 kg).

Homing phenotypes of tumor-specific CD8 T cells are predetermined at the tumor site by crosspresenting APCs.

Expression of tissue-specific homing molecules directs antigen-experienced T cells to particular peripheral tissues. In studies using soluble antigens that focused on skin and gut, antigen-presenting cells (APCs) within regional lymphoid tissues were proposed to be responsible for imprinting homing phenotypes. Whether this occurs in other sites and after physiologic antigen processing and presentation is unknown. We define in vivo imprinting of distinct homing phenotypes on monospecific T cells responding to antigens expressed by tumors in intracerebral, subcutaneous, and intraperitoneal sites with efficient brain-tropism of CD8 T cells crossprimed in the cervical lymph nodes (LNs). Multiple imprinting programs could occur simultaneously in the same LN when tumors were present in more than one site. Thus, the identity of the LN is not paramount in determining the homing phenotype; this critical functional parameter is dictated upstream at the site of antigen capture by crosspresenting APCs.

Multi-site -sertifikaatin vaatimukset ympäristöjohtamisjärjestelmän rakentamisessa

Diplomityö muodostuu kahdesta kokonaisuudesta. Työn teoriaosa kertoo mitä ympäristöjohtaminen on, millaisia ovat multi-site -organisaatio ja multi-site -johtamisjärjestelmä sekä mitä vaatimuksia nämä asettavat yritykselle. Työssä esitetään malli, jota käyttämällä kansainvälisten johtamisjärjestelmästandardien mukaan rakennetut laatu-, ympäristö-, terveys- ja turvallisuusjärjestelmät voidaan yhdistää yhdeksi kokonaisuudeksi, multi-site - johtamisjärjestelmäksi. Malli rakentuu kolmesta tasosta, joita ovat paikallinen, maakohtainen ja konsernitaso. Esimerkkien avulla kerrotaan miteneri lähtökohdista voidaan näiden tasojen kautta edetä kohti yhtä johtamiskokonaisuutta. Esille tuodaan myös multi-site -johtamisjärjestelmän käyttöönottoa puoltavat ja vastustavat näkökohdat. Työn konkreettinen osa on johtamisjärjestelmämallin paikallisen tason toteuttaminen. Ympäristöjohtamisjärjestelmän rakentaminen standardin EN ISO 14001:2004 vaatimusten mukaiseksi Kvaerner Power Oy:n Suomen toimipaikoille sekä tämän järjestelmän yhdistäminen sertifioituun EN ISO 9001 -standardin mukaiseen laatujärjestelmään. Työssä kerrotaan miten ympäristöjohtamisjärjestelmä on rakennettu ja miten laatu- ja ympäristöjärjestelmät on liitetty yhdeksi kokonaisuudeksi. Työn tuloksena syntyi malli johtamisjärjestelmien yhdistämisestä sekä sertifioitu ympäristöjohtamisjärjestelmä, jonka yhdistäminen laatujärjestelmään toteutettiin tavoitteiden mukaisesti.

LRCW.NET: A web site with a virtual laboratory for the study of coarse and cooking wares in the Late Antique Mediterranean

This contribution presents the LRCW.net a website with a virtual laboratory intranet devoted to the study of coarse and cooking wares in the late Antique Mediterranean. It is designed as a public website with a virtual laboratory intranet. There, all institutions and researchers interested in the subject can work together towards a specific purpose such as the creation of an on-line ‘encyclopedia’ for these categories of ceramics. The LRCW.net website and the associated virtual laboratory are just a small part of a wider initiative that aims to create an on-line Encyclopedia for Ancient Ceramics in the Mediterranean.

1,2,3,4-Tetrahydrobenzo[h][1,6]naphthyridines as a new family of potent peripheral-to-midgorge-site inhibitors of acetylcholinesterase: synthesis, pharmacological evaluation and mechanistic studies

A series of 1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridines differently substituted at positions 1, 5, and 9 have been designed from the pyrano[3,2-c]quinoline derivative 1, a weak inhibitor of acetylcholinesterase (AChE) with predicted ability to bind to the AChE peripheral anionic site (PAS), at the entrance of the catalytic gorge. Fourteen novel benzonaphthyridines have been synthesized through synthetic sequences involving as the key step a multicomponent Povarov reaction between an aldehyde, an aniline and an enamine or an enamide as the activated alkene. The novel compounds have been tested against Electrophorus electricus AChE (EeAChE), human recombinant AChE (hAChE), and human serum butyrylcholinesterase (hBChE), and their brain penetration has been assessed using the PAMPA-BBB assay. Also, the mechanism of AChE inhibition of the most potent compounds has been thoroughly studied by kinetic studies, a propidium displacement assay, and molecular modelling. We have found that a seemingly small structural change such as a double O → NH bioisosteric replacement from the hit 1 to 16a results in a dramatic increase of EeAChE and hAChE inhibitory activities (>217- and >154-fold, respectively), and in a notable increase in hBChE inhibitory activity (> 11-fold), as well. An optimized binding at the PAS besides additional interactions with AChE midgorge residues seem to account for the high hAChE inhibitory potency of 16a (IC50 = 65 nM), which emerges as an interesting anti-Alzheimer lead compound with potent dual AChE and BChE inhibitory activities.