Foxm1 expression in prostate epithelial cells is essential for prostate carcinogenesis.

The treatment of advanced prostate cancer (PCa) remains a challenge. Identification of new molecular mechanisms that regulate PCa initiation and progression would provide targets for the development of new cancer treatments. The Foxm1 transcription factor is highly up-regulated in tumor cells, inflammatory cells, and cells of tumor microenvironment. However, its functions in different cell populations of PCa lesions are unknown. To determine the role of Foxm1 in tumor cells during PCa development, we generated two novel transgenic mouse models, one exhibiting Foxm1 gain-of-function and one exhibiting Foxm1 loss-of-function under control of the prostate epithelial-specific Probasin promoter. In the transgenic adenocarcinoma mouse prostate (TRAMP) model of PCa that uses SV40 large T antigen to induce PCa, loss of Foxm1 decreased tumor growth and metastasis. Decreased prostate tumorigenesis was associated with a decrease in tumor cell proliferation and the down-regulation of genes critical for cell proliferation and tumor metastasis, including Cdc25b, Cyclin B1, Plk-1, Lox, and Versican. In addition, tumor-associated angiogenesis was decreased, coinciding with reduced Vegf-A expression. The mRNA and protein levels of 11β-Hsd2, an enzyme playing an important role in tumor cell proliferation, were down-regulated in Foxm1-deficient PCa tumors in vivo and in Foxm1-depleted TRAMP C2 cells in vitro. Foxm1 bound to, and increased transcriptional activity of, the mouse 11β-Hsd2 promoter through the -892/-879 region, indicating that 11β-Hsd2 was a direct transcriptional target of Foxm1. Without TRAMP, overexpression of Foxm1 either alone or in combination with inhibition of a p19(ARF) tumor suppressor caused a robust epithelial hyperplasia, but was insufficient to induce progression from hyperplasia to PCa. Foxm1 expression in prostate epithelial cells is critical for prostate carcinogenesis, suggesting that inhibition of Foxm1 is a promising therapeutic approach for prostate cancer chemotherapy.

The dmf1/mid1 gene is essential for correct positioning of the division septum in fission yeast.

Little is known about the mechanisms that establish the position of the division plane in eukaryotic cells. Wild-type fission yeast cells divide by forming a septum in the middle of the cell at the end of mitosis. Dmf1 mutants complete mitosis and initiate septum formation, but the septa that form are positioned at random locations and angles in the cell, rather than in the middle. We have cloned the dmf1 gene as a suppressor of the cdc7-24 mutant. The dmf1 mutant is allelic with mid1. The gene encodes a novel protein containing a putative nuclear localization signal, and a carboxy-terminal PH domain. In wild-type cells, Dmf1p is nuclear during interphase, and relocates to form a medial ring at the cell cortex coincident with the onset of mitosis. This relocalization occurs before formation of the actin ring and is associated with increased phosphorylation of Dmf1p. The Dmf1p ring can be formed in the absence of an actin ring, but depends on some of the genes required for actin ring formation. When the septum is completed and the cells separate, Dmf1p staining is once again nuclear. These data implicate Dmf1p as an important element in assuring correct placement of the division septum in Schizosaccharomyces pombe cells.

Evaluation of Cover Aggregate Stripping Characteristics, HR-182, 1979

The purpose of Research Project HR-182 was to identify those aggregate types which would perform satisfactorily as seal coat aggregates. Aggregates were chosen from across the State to represent the various types normally encountered and were used with two different types of binder bitumens. A water spray treatment was also included to simulate the effects of rainfall. The evaluation was based upon aggregate retention. Due to the influence of unexpected variables upon the field samples, the laboratory data are reliable for only the most general observations. Namely, that gravels as a group appear to be retained better than carbonates and rain-fall shortly after seal coat placement can affect aggregate retention. The subsequent field observations and analysis of skid resistance data permit the following conclusions: 1. Aggregate retention is influenced by lithologic type with the gravels, quartzite, haydite, dolomites, and medium grained limestones performing best. 2. Aggregate retention is not influenced by binder bitumen type. 3. Friction values of seal coats are influ-enced by aggregate retention and/or lithologic type. The following recommendations have been determined: The aggregate used for cover aggregate/seal coat projects should be Type 4 or better skid resistance as identified in Iowa DOT Materials Instructional Memorandum T-203. This will result in maximizing the possibility of good aggregate retention and skid resistance.

Model development for capercaillie (Tetrao urogallus) habitat in the Jura Mountains (Western Switzerland)

Capercaillie, Tetrao urogallus, is a threatened species in central Europe, and Swiss populations declined 40 to 50 % between 1970 and 1985. Capercaillie are sensitive to forest structure, and loss of habitat is a major cause of their decline. Knowledge of habitat characteristics is therefore essential for capercaillie conservation. Here, we present models predicting capercaillie probability of occurrence, based on relevant structural habitat variables. Models were built using multiple logistic regression analyses on capercaillie presence/absence data. Vegetation survey was carried out in July 1999 in a 170-km2 forested area (Jura mountains, canton de Vaud, western Switzerland) inhabited by capercaillie and presence/absence of the species was assessed according to dropping presence/absence. The survey was based on 10-m-radius sample plots each in a 1-km2 forest patch (n = 76 with capercaillie droppings, n = 80 without). A first model included seven out of 27 measured habitat variables and a second model only four. The latter model best represents practical needs. It includes three variables which had a negative impact on capercaillie presence: tree and shrub covers and spruce, Picea excelsa, shrub cover, and one which had a positive effect: bilberry, Vaccinium myrtillus, cover, highlighting that capaercaillie selected open forest with high bilberry abundance. The model can be used to map potential capercaillie habitat distribution and to manage the habitat in favour of capercaillie (protection and adapted forestry practices) in the Swiss Jura mountains.

Essential role of Smad3 in the inhibition of inflammation-induced PPARbeta/delta expression.

Wound healing proceeds by the concerted action of a variety of signals that have been well identified. However, the mechanisms integrating them and coordinating their effects are poorly known. Herein, we reveal how PPARbeta/delta (PPAR: peroxisome proliferator-activated receptor) follows a balanced pattern of expression controlled by a crosstalk between inflammatory cytokines and TGF-beta1. Whereas conditions that mimic the initial inflammatory events stimulate PPARbeta/delta expression, TGF-beta1/Smad3 suppresses this inflammation-induced PPARbeta/delta transcription, as seen in the late re-epithelialization/remodeling events. This TGF-beta1/Smad3 action involves an inhibitory effect on AP-1 activity and DNA binding that results in an inhibition of the AP-1-driven induction of the PPARbeta/delta promoter. As expected from these observations, wound biopsies from Smad3-null mice showed sustained PPARbeta expression as compared to those of their wild-type littermates. Together, these findings suggest a mechanism for setting the necessary balance between inflammatory signals, which trigger PPARbeta/delta expression, and TGF-beta1/Smad3 that governs the timely decrease of this expression as wound healing proceeds to completion.

U.S. landowner behavior, land use and land cover changes, and climate change mitigation

Abstract

An Evaluation of Cover Aggregate Stripping Characteristics, Progress Report, HR-182, 1977

The increasing use of seal coats for surface restoration and the concurrent increase in failures of such treatments prompted the current research. Field observations indicated that certain aggregate types seemed to be more susceptible to failure, including stripping and disintegration. The research was thus designed to try to identify those aggregate types which would perform satisfactorily under normal conditions.

Effect of intercropping wheat with forage legumes on wheat production and ground cover

The use of winter legumes in southern Brazil is hindered by the slow growth of these species during establishment exposing soil surface to erosion. Introduction of these species along with spring wheat (Triticum aestivum L.) was studied as a means of increasing ground cover during their initial establishment period, without reducing wheat grain yield. Two experiments were conducted in nearby areas, one in each year. Birdsfoot trefoil (Lotus corniculatus L.), red clover (Trifolium pratense L.) cultivar Quiñequelli, white clover (T. repens L.), and arrowleaf clover (T. vesiculosum Savi) did not reduce cereal yield in either year. Wheat yield was reduced by intercropped red clover cultivar Kenland and by subclover (T. subterraneum L.) in the first year. No grain yield differences due to intercropping with any legume were detected in the second year, when rainfall was below normal. Intercropping with wheat showed to be a practical alternative to enhance ground cover at establishing forage legumes.

BCL9 is an essential component of canonical Wnt signaling that mediates the differentiation of myogenic progenitors during muscle regeneration.

Muscle stem cells and their progeny play a fundamental role in the regeneration of adult skeletal muscle. We have previously shown that activation of the canonical Wnt/beta-catenin signaling pathway in adult myogenic progenitors is required for their transition from rapidly dividing transient amplifying cells to more differentiated progenitors. Whereas Wnt signaling in Drosophila is dependent on the presence of the co-regulator Legless, previous studies of the mammalian ortholog of Legless, BCL9 (and its homolog, BCL9-2), have not revealed an essential role of these proteins in Wnt signaling in specific tissues during development. Using Cre-lox technology to delete BCL9 and BCL9-2 in the myogenic lineage in vivo and RNAi technology to knockdown the protein levels in vitro, we show that BCL9 is required for activation of the Wnt/beta-catenin cascade in adult mammalian myogenic progenitors. We observed that the nuclear localization of beta-catenin and downstream TCF/LEF-mediated transcription, which are normally observed in myogenic progenitors upon addition of exogenous Wnt and during muscle regeneration, were abrogated when BCL9/9-2 levels were reduced. Furthermore, reductions of BCL9/9-2 inhibited the promotion of myogenic differentiation by Wnt and the normal regenerative response of skeletal muscle. These results suggest a critical role of BCL9/9-2 in the Wnt-mediated regulation of adult, as opposed to embryonic, myogenic progenitors.

Insecticidal, repellent, antimicrobial activity and phytotoxicity of essential oils: With special reference to limonene and its suitability for control of insect pests : Review

Selostus: Monoterpeenit kasvinsuojelussa: erityisesti limoneenin vaikutus eri eliöryhmiin

Essential residues in the H-NS binding site of Hha, a co-regulator of horizontally acquired genes in Enterobacteria

Proteins of the Hha/YmoA family co-regulate with H-NS the expression of horizontally acquired genes in Enterobacteria. Systematic mutations of conserved acidic residues in Hha have allowed the identification of D48 as an essential residue for H-NS binding and the involvement of E25. Mutations of these residues resulted in deregulation of sensitive genes in vivo. D48 is only partially solvent accessible, yet it defines the functional binding interface between Hha and H-NS confirming that Hha has to undergo a conformational change to bind H-NS. Exposed acidic residues, such as E25, may electrostatically facilitate and direct the approach of Hha to the positively charged region of H-NS enabling the formation of the final complex when D48 becomes accessible by a conformational change of Hha.

Phosphorus analysis in soil under herbaceous perennial leguminous cover by nuclear magnetic spectroscopy

The availability and the reserves of organic phosphorus are controlled by its mineralization rate and are also influenced by changes in soil management. The objective of this study was to evaluate the influence of soil covering with different leguminous plant on soil organic P by 31P-NMR spectroscopy. Alkaline soil extracts were obtained from two depths (0-5 and 5-10 cm) of an Ultisol cultivated with herbaceous perennial leguminous plants (Arachis pintoi, Pueraria phaseoloides, Macroptilium atropurpureum). In an adjacent area, samples of the same soil cover with a secondary tropical forest and grass (Panicum maximum) were also collected. The leguminous management was divided into with removal and without removal of shoot parts after cut on soil surface. Phosphate monoesters are the dominant P species in all soil samples and P diesters accumulated on the superficial layer of secondary forest soil. The P amount of this fraction is higher for the legume covered soil when compared with the grass covered soil. The permanence of leguminous plants on the topsoil after the cut promoted an increase in P diester/P monoester ratios. These findings can be accounted for an enhancement of P availability to plants in soils cultivated with leguminous plants.

Structure-function analysis of the human TFIIB-related factor II protein reveals an essential role for the C-terminal domain in RNA polymerase III transcription.

The transcription factors TFIIB, Brf1, and Brf2 share related N-terminal zinc ribbon and core domains. TFIIB bridges RNA polymerase II (Pol II) with the promoter-bound preinitiation complex, whereas Brf1 and Brf2 are involved, as part of activities also containing TBP and Bdp1 and referred to here as Brf1-TFIIIB and Brf2-TFIIIB, in the recruitment of Pol III. Brf1-TFIIIB recruits Pol III to type 1 and 2 promoters and Brf2-TFIIIB to type 3 promoters such as the human U6 promoter. Brf1 and Brf2 both have a C-terminal extension absent in TFIIB, but their C-terminal extensions are unrelated. In yeast Brf1, the C-terminal extension interacts with the TBP/TATA box complex and contributes to the recruitment of Bdp1. Here we have tested truncated Brf2, as well as Brf2/TFIIB chimeric proteins for U6 transcription and for assembly of U6 preinitiation complexes. Our results characterize functions of various human Brf2 domains and reveal that the C-terminal domain is required for efficient association of the protein with U6 promoter-bound TBP and SNAP(c), a type 3 promoter-specific transcription factor, and for efficient recruitment of Bdp1. This in turn suggests that the C-terminal extensions in Brf1 and Brf2 are crucial to specific recruitment of Pol III over Pol II.