bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors influencing large wildland fire suppression expenditures
Authors: Liang Jingjing , Calkin Dave E. , Gebert Krista M. , Venn Tyron J. , Silverstein Robin P.
Published: October 2008

There is an urgent and immediate need to address the excessive cost of large fires. Here, we studied large wildland fire suppression expenditures by the US Department of Agriculture Forest Service. Among 16 potential non-managerial factors, which represented fire size and shape, private properties, public land attributes, forest and fuel conditions, and geographic settings, we found only fire size and private land had a strong effect on suppression expenditures. When both were accounted for, all the other variables had no significant effect. A parsimonious model to predict suppression expenditures was suggested, in which fire size and private land explained 58% of variation in expenditures. Other things being equal, suppression expenditures monotonically increased with fire size. For the average fire size, expenditures first increased with the percentage of private land within burned area, but as the percentage exceeded 20%, expenditures slowly declined until they stabilised when private land reached 50% of burned area. The results suggested that efforts to contain federal suppression expenditures need to focus on the highly complex, politically sensitive topic of wildfires on private land.
The effect of ash on runoff and erosion after a severe forest wildfire, Montana, USA
Authors: Woods Scott W. , Balfour Victoria N.
Published: October 2008

Ash formed by the combustion of vegetation and the litter and duff layers may affect runoff and erosion rates in the period immediately following wildfires, but only a handful of studies have specifically measured its effect. Approximately 1 month after the 2005 Tarkio Fire in western Montana, we applied simulated rainfall for 1 h at a mean intensity of 7.5 cm h–1 to six pairs of 0.5-m2 plots in an area burned at high severity and with a continuous 1-cm to 3.5-cm ash layer on the surface. The ash was retained in one plot per pair and removed from the other plot with a fine brush. The ash layer provided an additional 1.5 cm of water storage capacity and protected the underlying mineral soil from surface sealing, so that the time of ponding in the ash-covered plots was 12 ± 10 min longer, the final runoff rate was 2.1 ± 0.4 cm h–1 lower and the total infiltration was 2.0 ± 1.2 cm higher than in the plots without ash. The reduced runoff from the ash-covered plots in combination with reduced rainsplash detachment resulted in a 74% reduction in sediment yield relative to the plots without ash. Nine months after the fire, the ash was patchy and just a few millimetres thick, and a second set of simulations showed no significant differences in the time of ponding, final runoff rate, total infiltration or sediment yield between plots with and without ash. Ash may significantly reduce the runoff and erosion from severely burned areas in the period shortly after a fire. Consequently, the largest post-fire hydrogeomorphic hazard will occur after the ash layer has been removed by wind and water erosion, but before there has been substantial vegetative regrowth.
Laboratory determination of factors influencing successful point ignition in the litter layer of shrubland vegetation
Authors: Plucinski Matt P. , Anderson Wendy R.
Published: October 2008

Factors affecting ignition thresholds of the litter layer of shrubland vegetation were investigated using reconstructed litter beds in a laboratory. The factors investigated were fuel moisture content (FMC), litter type (primarily species), pilot ignition source, and wind. Litter beds made from 11 different litter types were ignited with point ignition sources. Litter from Allocasuarina nana (Sieber ex Spreng.) L.A.S. Johnson was used as the standard type across all experiments. Successful ignition was defined as fire spreading a fixed distance from the ignition point. Ignition success was modelled as a logistic function of FMC. Litter type had a major effect on ignitibility. The bulk density of the litter bed and the surface area of litter per volume of litter bed provided reasonably good predictors of the effect of litter type on ignition success. Low-density litter beds ignited at higher FMCs than dense litter beds. The two densest litter beds failed to ignite with the procedures used here. The ignition sources tested had significantly different effects on ignition success. Larger ignition sources were able to ignite wetter fuels than smaller sources. The presence of wind was found to have a different effect on ignition success depending on the location of the ignition source with respect to the litter bed. Wind decreased ignition success when the ignition source was located on top of the litter bed, but aided ignition when the ignition source was located within the litter bed.
Effectiveness of aerial seeding and straw mulch for reducing post-wildfire erosion, north-western Montana, USA
Authors: Groen Amy H. , Woods Scott W.
Published: October 2008

Various methods are available to reduce post-wildfire erosion, but there is limited quantitative information on the relative effectiveness of these techniques. We used rainfall simulations to compare the erosion and runoff rates from adjacent 0.5-m2 plots treated with aerial grass seeding and straw mulch with untreated control plots following the July 2002 Fox Creek Fire in north-west Montana. In the first summer after the fire, plots seeded at a rate of 9 kg ha–1 had a mean of less than 5% ground cover and the seeding treatment had no effect on the rainsplash erosion rate. In contrast, straw mulch application at a rate of 2.24 Mg ha–1 resulted in ~100% ground cover and an 87% reduction in rainsplash erosion relative to the control (P = 0.001). Measurements on a subset of the plots in the second summer after the fire indicated that ground cover in the treatments and the control averaged 39%, and neither treatment provided a significant increase in ground cover or reduction in erosion relative to the control. These results add to the growing weight of evidence that straw mulch application is highly effective in reducing erosion in the first year after fire, whereas grass seeding is often ineffective because of the limited increase in ground cover that it produces.
Quantifying parametric uncertainty in the Rothermel model
Authors: Jimenez Edwin , Hussaini M. Yousuff , Goodrick Scott
Published: October 2008

The purpose of the present work is to quantify parametric uncertainty in the Rothermel wildland fire spread model (implemented in software such as BehavePlus3 and FARSITE), which is undoubtedly among the most widely used fire spread models in the United States. This model consists of a non-linear system of equations that relates environmental variables (input parameter groups) such as fuel type, fuel moisture, terrain, and wind to describe the fire environment. This model predicts important fire quantities (output parameters) such as the head rate of spread, spread direction, effective wind speed, and fireline intensity. The proposed method, which we call sensitivity derivative enhanced sampling, exploits sensitivity derivative information to accelerate the convergence of the classical Monte Carlo method. Coupled with traditional variance reduction procedures, it offers up to two orders of magnitude acceleration in convergence, which implies that two orders of magnitude fewer samples are required for a given level of accuracy. Thus, it provides an efficient method to quantify the impact of input uncertainties on the output parameters.
Recurrent wildfires constrain long-term reproduction ability in Pinus halepensis Mill.
Authors: Espelta Josep Maria , Verkaik Iraima , Eugenio Màrcia , Lloret Francisco
Published: October 2008

Increasing fire recurrence is a major problem threatening Mediterranean-type ecosystems. Moreover, this pattern is predicted to increase owing to global change. Although a reduction in the density and growth of post-fire regeneration is usually observed in recurrently burnt areas, the potential effects on reproductive ability have seldom been explored. The aim of the present study is to investigate whether structural changes induced by fire recurrence may constrain reproduction ability of Pinus halepensis forests. We conducted the current study in Catalonia (NE Spain) in 12 study sites, consisting of two adjacent areas differing in the number of fire events suffered throughout the last 16 years (one v. two fires). Twice-burnt areas showed a lower density of pines, lower pine height and a lower reproductive ability, namely (i) a 3-year delay in the onset of pine reproduction; (ii) a reduction of 52% in the number of reproductive pines; and (iii) a 36% lower mean cone crop per tree. The lower mean cone production per tree coupled with a lower density resulted in an ~80% lower canopy seed bank in twice-burnt areas. These results suggest that the occurrence of a third fire event in twice-burnt areas would severely constrain natural regeneration.
Manager-based valuations of alternative fire management regimes on Cape York Peninsula, Australia
Authors: Drucker Adam G. , Garnett Stephen T. , Luckert Marty K. , Crowley Gabriel M. , Gobius Niilo
Published: October 2008

Decisions about fire management on pastoral properties are often made with little empirical knowledge. Proper accounting of the interactions between land, pasture, trees and livestock within the context of climatic variability and market conditions is required in order to assess financial implications of alternative fire management regimes. The present paper aims to facilitate such accounting through the development of a manager-driven decision-support tool. This approach is needed to account for variable property conditions and to provide direction towards considering optimal practices among a vast array of potential activities. The tool is an interactive model, developed for a hypothetical property, which analyses the costs and benefits of a baseline (no fires) against a historically based probability of wildfire overlaid by four alternative fire management regimes, representing cumulatively increasing levels of fire management intensity. These are: Regime 1, no action taken to prevent or stop wildfires; Regime 2, fire suppression (reactive fighting of wildfire); Regime 3, Regime 2 plus prevention (early dry-season burning); and Regime 4, Regime 3 combined with storm-burning (burning soon after the first wet-season storm). The model, which shows that fire and fire management have significant influences on the gross margin of Cape York Peninsula cattle properties, can be used as a decision-support tool in developing fire management strategies for individual properties. Specific fire management recommendations follow, together with the identification of potential areas of future work needed to facilitate use of the tool by clients.
Rapid Virulence Annotation (RVA): Identification of virulence factors using a bacterial genome library and multiple invertebrate hosts
Authors: Waterfield Nicholas R. , Sanchez-Contreras Maria , Eleftherianos Ioannis , Dowling Andrea , Yang Guowei , Wilkinson Paul , Parkhill Julian , Thomson Nicholas , Reynolds Stuart E. , Bode Helge B. , Dorus Steven , ffrench-Constant Richard H.
Published: October 2008

Current sequence databases now contain numerous whole genome sequences of pathogenic bacteria. However, many of the predicted genes lack any functional annotation. We describe an assumption-free approach, Rapid Virulence Annotation (RVA), for the high-throughput parallel screening of genomic libraries against four different taxa: insects, nematodes, amoeba, and mammalian macrophages. These hosts represent different aspects of both the vertebrate and invertebrate immune system. Here, we apply RVA to the emerging human pathogen
Photorhabdus asymbiotica
using “gain of toxicity” assays of recombinant
Escherichia coli
clones. We describe a wealth of potential virulence loci and attribute biological function to several putative genomic islands, which may then be further characterized using conventional molecular techniques. The application of RVA to other pathogen genomes promises to ascribe biological function to otherwise uncharacterized virulence genes.
Temperature increase of 21st century mitigation scenarios
Authors: Van Vuuren D. P. , Meinshausen M. , Plattner G.-K. , Joos F. , Strassmann K. M. , Smith S. J. , Wigley T. M. L. , Raper S. C. B. , Riahi K. , de la Chesnaye F. , den Elzen M. G. J. , Fujino J. , Jiang K. , Nakicenovic N. , Paltsev S. , Reilly J. M.
Published: October 2008

Estimates of 21st Century global-mean surface temperature increase have generally been based on scenarios that do not include climate policies. Newly developed multigas mitigation scenarios, based on a wide range of modeling approaches and socioeconomic assumptions, now allow the assessment of possible impacts of climate policies on projected warming ranges. This article assesses the atmospheric CO
2
concentrations, radiative forcing, and temperature increase for these new scenarios using two reduced-complexity climate models. These scenarios result in temperature increase of 0.5–4.4°C over 1990 levels or 0.3–3.4°C less than the no-policy cases. The range results from differences in the assumed stringency of climate policy and uncertainty in our understanding of the climate system. Notably, an average minimum warming of ≈1.4°C (with a full range of 0.5–2.8°C) remains for even the most stringent stabilization scenarios analyzed here. This value is substantially above previously estimated committed warming based on climate system inertia alone. The results show that, although ambitious mitigation efforts can significantly reduce global warming, adaptation measures will be needed in addition to mitigation to reduce the impact of the residual warming.
Combination therapy with AT1 blocker and vitamin D analog markedly ameliorates diabetic nephropathy: Blockade of compensatory renin increase
Authors: Zhang Zhongyi , Zhang Yan , Ning Gang , Deb Dilip K. , Kong Juan , Li Yan Chun
Published: October 2008

The renin–angiotensin system (RAS) plays a critical role in the development of diabetic nephropathy, and blockade of the RAS is currently used for treatment of diabetic nephropathy. One major problem for the current RAS inhibitors is the compensatory renin increase, which reduces the efficacy of RAS inhibition. We have shown that vitamin D exerts renoprotective actions by transcriptionally suppressing renin. Here we demonstrated that combination therapy with an AT1 receptor blocker and a vitamin D analog markedly ameliorated renal injury in the streptozotocin (STZ)-induced diabetes model due to the blockade of the compensatory renin rise by the vitamin D analog, leading to more effective RAS inhibition. STZ-treated diabetic DBA/2J mice developed progressive albuminuria and glomerulosclerosis within 13 weeks, accompanied by increased intrarenal production of angiotensin (Ang) II, fibronection, TGF-β, and MCP-1 and decreased expression of slit diaphragm proteins. Treatment of the diabetic mice with losartan or paricalcitol (19-nor-1,25-dihydroxyvitamin D
2
, an activated vitamin D analog) alone moderately ameliorated kidney injury; however, combined treatment with losartan and paricalcitol completely prevented albuminuria, restored glomerular filtration barrier structure, and markedly reduced glomerulosclerosis. The combined treatment suppressed the induction of fibronection, TGF-β, and MCP-1 and reversed the decline of slit diaphragm proteins nephrin, Neph-1, ZO-1, and α-actinin-4. These were accompanied by blockade of intrarenal renin and Ang II accumulation induced by hyperglycemia and losartan. These data demonstrate that inhibition of the RAS with combination of vitamin D analogs and RAS inhibitors effectively prevents renal injury in diabetic nephropathy.
Oviduct-specific glycoprotein and heparin modulate sperm–zona pellucida interaction during fertilization and contribute to the control of polyspermy
Authors: Coy Pilar , Cánovas Sebastián , Mondéjar Irene , Saavedra Maria Dolores , Romar Raquel , Grullón Luis , Matás Carmen , Avilés Manuel
Published: October 2008

Polyspermy is an important anomaly of fertilization in placental mammals, causing premature death of the embryo. It is especially frequent under
in vitro
conditions, complicating the successful generation of viable embryos. A block to polyspermy develops as a result of changes after sperm entry (i.e., cortical granule exocytosis). However, additional factors may play an important role in regulating polyspermy by acting on gametes before sperm–oocyte interaction. Most studies have used rodents as models, but ungulates may differ in mechanisms preventing polyspermy. We hypothesize that zona pellucida (ZP) changes during transit of the oocyte along the oviductal ampulla modulate the interaction with spermatozoa, contributing to the regulation of polyspermy. We report here that periovulatory oviductal fluid (OF) from sows and heifers increases (both, con- and heterospecifically) ZP resistance to digestion with pronase (a parameter commonly used to measure the block to polyspermy), changing from digestion times of ≈1 min (pig) or 2 min (cattle) to 45 min (pig) or several hours (cattle). Exposure of oocytes to OF increases monospermy after
in vitro
fertilization in both species, and in pigs, sperm–ZP binding decreases. The resistance of OF-exposed oocytes to pronase was abolished by exposure to heparin-depleted medium; in a medium with heparin it was not altered. Proteomic analysis of the content released in the heparin-depleted medium after removal of OF-exposed oocytes allowed the isolation and identification of oviduct-specific glycoprotein. Thus, an oviduct-specific glycoprotein–heparin protein complex seems to be responsible for ZP changes in the oviduct before fertilization, affecting sperm binding and contributing to the regulation of polyspermy.
Anisotropic rheology and directional mechanotransduction in vascular endothelial cells
Authors: del Álamo Juan C. , Norwich Gerard N. , Li Yi-shuan Julie , Lasheras Juan C. , Chien Shu
Published: October 2008

Adherent cells remodel their cytoskeleton, including its directionality, in response to directional mechanical stimuli with consequent redistribution of intracellular forces and modulation of cell function. We analyzed the temporal and spatial changes in magnitude and directionality of the cytoplasmic creep compliance (Γ) in confluent cultures of bovine aortic endothelial cells subjected to continuous laminar flow shear stresses. We extended particle tracking microrheology to determine at each point in the cytoplasm the principal directions along which Γ is maximal and minimal. Under static condition, the cells have polygonal shapes without specific alignment. Although Γ of each cell exhibits directionality with varying principal directions, Γ averaged over the whole cell population is isotropic. After continuous laminar flow shear stresses, all cells gradually elongate and the directions of maximal and minimal Γ become, respectively, parallel and perpendicular to flow direction. This mechanical alignment is accompanied by a transition of the cytoplasm to be more fluid-like along the flow direction and more solid-like along the perpendicular direction; at the same time Γ increases at the downstream part of the cells. The resulting directional anisotropy and spatial inhomogeneity of cytoplasmic rheology may play an important role in mechanotransduction in adherent cells by providing a means to sense the direction of mechanical stimuli.
Parallel pathways of repression and antirepression governing the transition to stationary phase in
Bacillus subtilis
Authors: Banse Allison V. , Chastanet Arnaud , Rahn-Lee Lilah , Hobbs Errett C. , Losick Richard
Published: October 2008

The AbrB protein of the spore-forming bacterium
Bacillus subtilis
is a repressor of numerous genes that are switched on during the transition from the exponential to the stationary phase of growth. The gene for AbrB is under the negative control of the master regulator for entry into sporulation, Spo0A∼P. It has generally been assumed that derepression of genes under the negative control of AbrB is achieved by Spo0A∼P-mediated repression of
abrB
followed by rapid degradation of the AbrB protein. Here, we report that AbrB levels do decrease during the transition to stationary phase, but that this decrease is not the entire basis by which AbrB-controlled genes are derepressed. Instead, AbrB is inactivated by the product of a uncharacterized gene,
abbA
(formerly
ykzF
), whose transcription is switched on by Spo0A∼P. The
abbA
gene encodes an antirepressor that binds to AbrB and prevents it from binding to DNA. Combining our results with previous findings, we conclude that Spo0A∼P sets in motion two parallel pathways of repression and antirepression to trigger the expression of diverse categories of genes during the transition to stationary phase.
Genome-wide studies highlight indirect links between human replication origins and gene regulation
Authors: Cadoret Jean-Charles , Meisch Françoise , Hassan-Zadeh Vahideh , Luyten Isabelle , Guillet Claire , Duret Laurent , Quesneville Hadi , Prioleau Marie-Noëlle
Published: October 2008

To get insights into the regulation of replication initiation, we systematically mapped replication origins along 1% of the human genome in HeLa cells. We identified 283 origins, 10 times more than previously known. Origin density is strongly correlated with genomic landscapes, with clusters of closely spaced origins in GC-rich regions and no origins in large GC-poor regions. Origin sequences are evolutionarily conserved, and half of them map within or near CpG islands. Most of the origins overlap transcriptional regulatory elements, providing further evidence of a connection with gene regulation. Moreover, we identify c-JUN and c-FOS as important regulators of origin selection. Half of the identified replication initiation sites do not have an open chromatin configuration, showing the absence of a direct link with gene regulation. Replication timing analyses coupled with our origin mapping suggest that a relatively strict origin-timing program regulates the replication of the human genome.
Inhibition of Hsp90 activates osteoclast c-Src signaling and promotes growth of prostate carcinoma cells in bone
Authors: Yano Akihiro , Tsutsumi Shinji , Soga Shiro , Lee Min-Jung , Trepel Jane , Osada Hiroyuki , Neckers Len
Published: October 2008

Hsp90 inhibitors are being evaluated extensively in patients with advanced cancers. However, the impact of Hsp90 inhibition on signaling pathways in normal tissues and the effect that this may have on the antitumor activity of these molecularly targeted drugs have not been rigorously examined. Breast and prostate carcinomas are among those cancers that respond to Hsp90 inhibitors in animal xenograft models and in early studies in patients. Because these cancers frequently metastasize to bone, it is important to determine the impact of Hsp90 inhibitors in the bone environment. In the current study, we show that, in contrast to its activity against prostate cancer cells
in vitro
and its inhibition of s.c. prostate cancer xenografts, the Hsp90 inhibitor 17-AAG stimulates the intraosseous growth of PC-3M prostate carcinoma cells. This activity is mediated not by a direct effect on the tumor but by Hsp90-dependent stimulation of osteoclast maturation. Hsp90 inhibition transiently activates osteoclast Src kinase and promotes Src-dependent Akt activation. Both kinases are key drivers of osteoclast maturation, and three agents that block osteoclastogenesis, the Src inhibitor dasatinib, the bisphosphonate alendronate, and the osteoclast-specific apoptosis-inducer reveromycin A, markedly reduced 17-AAG-stimulated tumor growth in bone. These data emphasize the importance of understanding the complex role played by Hsp90 in regulating signal transduction pathways in normal tissues as well as in cancer cells, and they demonstrate that drug-dependent modulation of the local tumor environment may profoundly affect the antitumor efficacy of Hsp90-directed therapy.
Atom by atom: HRTEM insights into inorganic nanotubes and fullerene-like structures
Authors: Sadan Maya Bar , Houben Lothar , Enyashin Andrey N. , Seifert Gotthard , Tenne Reshef
Published: October 2008

The characterization of nanostructures down to the atomic scale is essential to understand some physical properties. Such a characterization is possible today using direct imaging methods such as aberration-corrected high-resolution transmission electron microscopy (HRTEM), when iteratively backed by advanced modeling produced by theoretical structure calculations and image calculations. Aberration-corrected HRTEM is therefore extremely useful for investigating low-dimensional structures, such as inorganic fullerene-like particles and inorganic nanotubes. The atomic arrangement in these nanostructures can lead to new insights into the growth mechanism or physical properties, where imminent commercial applications are unfolding. This article will focus on two structures that are symmetric and reproducible. The first structure that will be dealt with is the smallest stable symmetric closed-cage structure in the inorganic system, a MoS
2
nanooctahedron. It is investigated by means of aberration-corrected microscopy which allowed validating the suggested DFTB-MD model. It will be shown that structures diverging from the energetically most stable structures are present in the laser ablated soot and that the alignment of the different shells is parallel, unlike the bulk material where the alignment is antiparallel. These findings correspond well with the high-energy synthetic route and they provide more insight into the growth mechanism. The second structure studied is WS
2
nanotubes, which have already been shown to have a unique structure with very desirable mechanical properties. The joint HRTEM study combined with modeling reveals new information regarding the chirality of the different shells and provides a better understanding of their growth mechanism.
Evolutionary emergence of responsive and unresponsive personalities
Authors: Wolf Max , van Doorn G. Sander , Weissing Franz J.
Published: October 2008

In many animal species, individuals differ consistently in suites of correlated behaviors, comparable with human personalities. Increasing evidence suggests that one of the fundamental factors structuring personality differences is the responsiveness of individuals to environmental stimuli. Whereas some individuals tend to be highly responsive to such stimuli, others are unresponsive and show routine-like behaviors. Much research has focused on the proximate causes of these differences but little is known about their evolutionary origin. Here, we provide an evolutionary explanation. We develop a simple but general evolutionary model that is based on two key ingredients. First, the benefits of responsiveness are frequency-dependent; that is, being responsive is advantageous when rare but disadvantageous when common. This explains why responsive and unresponsive individuals can coexist within a population. Second, positive-feedback mechanisms reduce the costs of responsiveness; that is, responsiveness is less costly for individuals that have been responsive before. This explains why individuals differ consistently in their responsiveness, across contexts and over time. As a result, natural selection gives rise to stable individual differences in responsiveness. Whereas some individuals respond to environmental stimuli in all kinds of contexts, others consistently neglect such stimuli. Interestingly, such differences induce correlations among all kinds of other traits (e.g., boldness and aggressiveness), thus providing an explanation for environment-specific behavioral syndromes.
Developmental plasticity of cutaneous water loss and lipid composition in stratum corneum of desert and mesic nestling house sparrows
Authors: Muñoz-Garcia Agustí , Williams Joseph B.
Published: October 2008

Intercellular lipids of the stratum corneum (SC), the outer layer of the epidermis, form a barrier to water vapor diffusion through the skin. Previously, we measured cutaneous water loss (CWL) and lipid composition of the SC of adult house sparrows from two populations, one living in the deserts of Saudi Arabia and another living in mesic Ohio. Adult desert house sparrows had a lower CWL, a lower proportion of free fatty acids, and a higher proportion of ceramides and cerebrosides in the SC compared with mesic sparrows. In this study, we investigated developmental plasticity of CWL and lipid composition of the SC in desert and mesic nestling house sparrows reared in low and high humidity and compared our results with previous work on adults. We measured CWL of nestlings and analyzed the lipid composition of the SC using thin-layer chromatography. We showed that nestling house sparrows from both localities had higher CWL than adults in their natural environment, a result of major modifications of the lipid composition of the SC. The expression of plasticity in CWL seems to be a response to opposed selection pressures, thermoregulation and water conservation, at different life stages, on which regulation of CWL plays a crucial role. Desert nestlings showed a greater degree of plasticity in CWL and lipid composition of the SC than did mesic nestlings, a finding consistent with the idea that organisms exposed to more environmental stress ought to be more plastic than individuals living in more benign environments.
Implantation of the human embryo requires Rac1-dependent endometrial stromal cell migration
Authors: Grewal Seema , Carver Janet G. , Ridley Anne J. , Mardon Helen J.
Published: October 2008

Failure of the human embryo to implant into the uterine wall during the early stages of pregnancy is a major cause of infertility. Implantation involves embryo apposition and adhesion to the endometrial epithelium followed by penetration through the epithelium and invasion of the embryonic trophoblast through the endometrial stroma. Although gene-knockdown studies have highlighted several molecules that are important for implantation in the mouse, the molecular mechanisms controlling implantation in the human are unknown. Here, we demonstrate in an
in vitro
model for human implantation that the Rho GTPases Rac1 and RhoA in human endometrial stromal cells modulate invasion of the human embryo through the endometrial stroma. We show that knockdown of Rac1 expression in human endometrial stromal cells inhibits human embryonic trophoblast invasion into stromal cell monolayers, whereas inhibition of RhoA activity promotes embryo invasion. Furthermore, we demonstrate that Rac1 is required for human endometrial stromal cell migration and that the motility of the stromal cells increases at implantation sites. This increased motility correlates with a localized increase in Rac1 activation and a reciprocal decrease in RacGAP1 levels. These results reveal embryo-induced and localized endometrial responses that may govern implantation of the human embryo.
A farnesyltransferase inhibitor prevents both the onset and late progression of cardiovascular disease in a progeria mouse model
Authors: Capell Brian C. , Olive Michelle , Erdos Michael R. , Cao Kan , Faddah Dina A. , Tavarez Urraca L. , Conneely Karen N. , Qu Xuan , San Hong , Ganesh Santhi K. , Chen Xiaoyan , Avallone Hedwig , Kolodgie Frank D. , Virmani Renu , Nabel Elizabeth G. , Collins Francis S.
Published: October 2008

Hutchinson-Gilford progeria syndrome (HGPS) is the most dramatic form of human premature aging. Death occurs at a mean age of 13 years, usually from heart attack or stroke. Almost all cases of HGPS are caused by a
de novo
point mutation in the lamin A (
LMNA
) gene that results in production of a mutant lamin A protein termed progerin. This protein is permanently modified by a lipid farnesyl group, and acts as a dominant negative, disrupting nuclear structure. Treatment with farnesyltransferase inhibitors (FTIs) has been shown to prevent and even reverse this nuclear abnormality in cultured HGPS fibroblasts. We have previously created a mouse model of HGPS that shows progressive loss of vascular smooth muscle cells in the media of the large arteries, in a pattern that is strikingly similar to the cardiovascular disease seen in patients with HGPS. Here we show that the dose-dependent administration of the FTI tipifarnib (R115777, Zarnestra) to this HGPS mouse model can significantly prevent both the onset of the cardiovascular phenotype as well as the late progression of existing cardiovascular disease. These observations provide encouraging evidence for the current clinical trial of FTIs for this rare and devastating disease.
The variable immunological self: Genetic variation and nongenetic noise in Aire-regulated transcription
Authors: Venanzi Emily S. , Melamed Rachel , Mathis Diane , Benoist Christophe
Published: October 2008

The Aire transcription factor plays an important role in immunological self-tolerance by mediating the ectopic expression of peripheral self-antigens by thymic medullary epithelial cells (MECs), and the deletion of thymocytes that recognize them. In Aire-deficient humans or mice, central tolerance is incomplete and multiorgan autoimmune disease results. We examined the variability of Aire's effects on ectopic transcription among individual mice of three different inbred strains. Aire's function was, overall, quite similar in the three backgrounds, although generally stronger in C57BL/6 than in BALB/c or NOD mice, and a minority of Aire-regulated genes did show clear differences. Gene expression profiling of wild-type MECs from single mice, or from the two thymic lobes of the same mouse, revealed significantly greater variability in Aire-controlled ectopic gene expression than in Aire-independent transcripts. This “noisy” ectopic expression did not result from parental or early developmental imprinting, but from programming occurring after the formation of the thymic anlage, resulting from epigenetic effects or from the stochastic nature of Aire activity. Together, genetic and nongenetic variability in ectopic expression of peripheral antigens in the thymus make for differences in the portion of self determinants presented for tolerance induction. This variable self may be beneficial in preventing uniform holes in the T-cell repertoire in individuals of a species, but at the cost of variable susceptibility to autoimmunity.
Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria
Authors: Cereghetti G. M. , Stangherlin A. , de Brito O. Martins , Chang C. R. , Blackstone C. , Bernardi P. , Scorrano L.
Published: October 2008

Changes in mitochondrial morphology that occur during cell cycle, differentiation, and death are tightly regulated by the balance between fusion and fission processes. Excessive fragmentation can be caused by inhibition of the fusion machinery and is a common consequence of dysfunction of the organelle. Here, we show a role for calcineurin-dependent translocation of the profission dynamin related protein 1 (Drp1) to mitochondria in dysfunction-induced fragmentation. When mitochondrial depolarization is associated with sustained cytosolic Ca
2+
rise, it activates the cytosolic phosphatase calcineurin that normally interacts with Drp1. Calcineurin-dependent dephosphorylation of Drp1, and in particular of its conserved serine 637, regulates its translocation to mitochondria as substantiated by site directed mutagenesis. Thus, fragmentation of depolarized mitochondria depends on a loop involving sustained Ca
2+
rise, activation of calcineurin, and dephosphorylation of Drp1 and its translocation to the organelle.
Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood
Authors: Fan H. Christina , Blumenfeld Yair J. , Chitkara Usha , Hudgins Louanne , Quake Stephen R.
Published: October 2008

We directly sequenced cell-free DNA with high-throughput shotgun sequencing technology from plasma of pregnant women, obtaining, on average, 5 million sequence tags per patient sample. This enabled us to measure the over- and underrepresentation of chromosomes from an aneuploid fetus. The sequencing approach is polymorphism-independent and therefore universally applicable for the noninvasive detection of fetal aneuploidy. Using this method, we successfully identified all nine cases of trisomy 21 (Down syndrome), two cases of trisomy 18 (Edward syndrome), and one case of trisomy 13 (Patau syndrome) in a cohort of 18 normal and aneuploid pregnancies; trisomy was detected at gestational ages as early as the 14th week. Direct sequencing also allowed us to study the characteristics of cell-free plasma DNA, and we found evidence that this DNA is enriched for sequences from nucleosomes.
Coordinate regulation of enzyme markers for inflammation and for protection against oxidants and electrophiles
Authors: Liu Hua , Dinkova-Kostova Albena T. , Talalay Paul
Published: October 2008

An elaborate network of highly inducible phase 2 proteins protects aerobic cells against the cumulative damaging effects of reactive oxygen intermediates and toxic electrophiles, which are the major causes of malignancy and chronic degenerative diseases. Many chemical and phytochemical agents, all of which react with thiol groups, induce the phase 2 response through their reactivity with critical cysteine thiols of Keap1. We recently found that the anti-inflammatory potencies (suppression of iNOS and COX-2 expression) of a series of triterpenoids with Michael reaction centers were closely correlated with the potencies of these agents to induce the phase 2 response. We now report that representatives of seven recognized chemical classes of inducers, including isothiocyanates, bisbenzylidenes, arsenicals, heavy metals, and vicinal dithiols, showed highly correlated inducer and anti-inflammatory potencies spanning more than six orders of magnitude of concentrations in established cells and in primary mouse peritoneal macrophages. Potency measurements were expressed as the

D
m

values (median effect concentration) by use of the Median Effect Equation. Whereas the phase 2 induction required the functional integrity of both the repressor Keap1 and the transcription factor Nrf2, the effectiveness of inducers in blocking the up-regulation of iNOS by inflammatory cytokines was related to the nature of the cytokine and the inducer concentration. These studies identify suppression of inflammation as a consistent property of inducers of the phase 2 response and strongly suggest that this property is a central aspect of their chemoprotective actions.
A functional nitric oxide reductase model
Authors: Collman James P. , Yang Ying , Dey Abhishek , Decréau Richard A. , Ghosh Somdatta , Ohta Takehiro , Solomon Edward I.
Published: October 2008

A functional heme/nonheme nitric oxide reductase (NOR) model is presented. The fully reduced diiron compound reacts with two equivalents of NO leading to the formation of one equivalent of N
2
O and the bis-ferric product. NO binds to both heme Fe and nonheme Fe complexes forming individual ferrous nitrosyl species. The mixed-valence species with an oxidized heme and a reduced nonheme Fe
B
does not show NO reduction activity. These results are consistent with a so-called “
trans
” mechanism for the reduction of NO by bacterial NOR.
TLR3 is an endogenous sensor of tissue necrosis during acute inflammatory events
Authors: Cavassani Karen A. , Ishii Makoto , Wen Haitao , Schaller Matthew A. , Lincoln Pamela M. , Lukacs Nicholas W. , Hogaboam Cory M. , Kunkel Steven L.
Published: October 2008

Ligands from dying cells are a source of Toll-like receptor (TLR) activating agents. Although TLR3 is known to respond to RNA from necrotic cells, the relative importance of this response in vivo during acute inflammatory processes has not been fully explored. We observed the involvement of TLR3 activation during experimental polymicrobial septic peritonitis and ischemic gut injury in the absence of an exogenous viral stimulus. In TLR3-deficient mice, increased chemokine/cytokine levels and neutrophil recruitment characterized the initial inflammatory responses in both injury models. However, the levels of inflammatory chemokines and tumor necrosis factor α quickly returned to baseline in tlr3−/− mice, and these mice were protected from the lethal effects of sustained inflammation. Macrophages from tlr3−/− mice responded normally to other TLR ligands but did not respond to RNA from necrotic neutrophils. Importantly, an immunoneutralizing antibody directed against TLR3 attenuated the generation of inflammatory chemokines evoked by byproducts from necrotic neutrophils cultured with wild-type macrophages. In vivo, anti-TLR3 antibody attenuated the tissue injury associated with gut ischemia and significantly decreased sepsis-induced mortality. Collectively, these data show that TLR3 is a regulator of the amplification of immune response and serves an endogenous sensor of necrosis, independent of viral activation.
Executive Summary: A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals
Authors: Yokoe Deborah S. , Mermel Leonard A. , Anderson Deverick J. , Arias Kathleen M. , Burstin Helen , Calfee David P. , Coffin Susan E. , Dubberke Erik R. , Fraser Victoria , Gerding Dale N. , Griffin Frances A. , Gross Peter , Kaye Keith S. , Klompas Michael , Lo Evelyn , Marschall Jonas , Nicolle Lindsay , Pegues David A. , Perl Trish M. , Podgorny Kelly , Saint Sanjay , Salgado Cassandra D. , Weinstein Robert A. , Wise Robert , Classen David
Published: October 2008

Preventable healthcare-associated infections (HAIs) occur in US hospitals. Preventing these infections is a national priority, with initiatives led by healthcare organizations, professional associations, government and accrediting agencies, legislators, regulators, payers, and consumer advocacy groups. To assist acute care hospitals in focusing and prioritizing efforts to implement evidence-based practices for prevention of HAIs, the Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America Standards and Practice Guidelines Committee appointed a task force to create a concise compendium of recommendations for the prevention of common HAIs. This compendium is implementation focused and differs from most previously published guidelines in that it highlights a set of basic HAI prevention strategies plus special approaches for use in locations and/or populations within the hospital when infections are not controlled by use of basic practices, recommends that accountability for implementing infection prevention practices be assigned to specific groups and individuals, and includes proposed performance measures for internal quality improvement efforts.
Introduction: Improving Patient Safety Through Infection Control: A New Healthcare Imperative
Authors: Yokoe Deborah S. , Classen David
Published: October 2008

Many healthcare organizations, professional associations, government and accrediting agencies, legislators, regulators, payers, and consumer advocacy groups have advanced the prevention of healthcare-associated infections as a national imperative, stimulating the creation of “A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals” in this supplement. In this introduction, we provide background and context and discuss the major issues that shaped the recommendations included in the compendium.
Signaller: receiver coordination and the timing of communication in Amazonian birds
Authors: Luther David A
Published: October 2008

The efficacy of communication relies on the detection of signals against background noise. Some species are known to alter the timing of vocalizations to avoid acoustic interference from similar signals of other species, but nothing is known about the possibility of coordinated adjustments in the timing of receivers' attention. I examined the possibility that co-occurring species might respond as well as vocalize at different times in a diverse tropical avifauna by presenting playbacks of recordings to territorial birds at typical and atypical times for singing during the dawn chorus. The results show that co-occurring species of birds in a diverse avifauna partition the timing of both production and response in a way that would reduce acoustic interference between species.
Life history of a basal bird: morphometrics of the Early Cretaceous
Confuciusornis
Authors: Chiappe Luis M , Marugán-Lobón Jesús , Ji Shu'an , Zhou Zhonghe
Published: October 2008

Confuciusornis sanctus
stands out among the remarkable diversity of Mesozoic birds recently unearthed from China. Not only is this primitive beaked pygostylian (birds with abbreviated caudal vertebrae fused into a pygostyle) much more abundant than other avian taxa of this age but differences in plumage between specimens—some having a pair of long stiff tail feathers—have been interpreted as evidence for the earliest example of sexual dimorphism in birds. We report the results of a multivariate morphometric study involving measurements of more than 100 skeletons of
C. sanctus
. Our analyses do not show any correlation between size distribution and the presence or absence of blade-like rectrices (tail feathers), thus implying, that if these feathers are sexual characters, they are not correlated with sexual size dimorphism. Our results also provide insights into the taxonomy and life history of confuciusornithids, suggesting that these birds may have retained ancestral dinosaurian growth patterns characterized by a midlife exponential growth stage.
A threat to coral reefs multiplied? Four species of crown-of-thorns starfish
Authors: Vogler Catherine , Benzie John , Lessios Harilaos , Barber Paul , Wörheide Gert
Published: October 2008

In the face of ever-increasing threats to coral reef ecosystems, it is essential to understand the impact of natural predators in order to devise appropriate management strategies. Destructive population explosions of the crown-of-thorns starfishAcanthaster plancihave devastated coral reefs throughout the Indo-Pacific for decades. But despite extensive research, the causes of outbreaks are still unclear. An important consideration in this research is thatA. plancihas been regarded as a single taxonomic entity. Using molecular data from its entire distribution, we find thatA. planciis in fact a species complex. This discovery has important consequences for future coral reef research, and might prove critical for successful reef conservation management.
Schoenoplectus corymbosus: a tropical Old‐World sedge (Cyperaceae) discovered in Spain and Morocco
Authors: Jiménez‐Mejías Pedro , Luceño Modesto , Castroviejo Santiago
Published: October 2008

Schoenoplectus corymbosusis a sedge from tropical wetlands widely distributed in Pakistan, India and Africa. Recent collections confirm its presence in wetlands of southern Spain and Morocco. We consider the presence of this plant in the western extreme of the Mediterranean as a consequence of recent colonization, because it was not collected here until 1999, in spite of its medium–large size. Additionally, it grows in much visited areas like nature reserves (such as Doñana National Park). The populations from Spain and Morocco are characterized here, a description ofS.corymbosusand a key forSchoenoplectusfrom Europe and north Africa is supplied. Finally, the possible natural and recent colonization processes of these new populations are discussed.
Validation of Prunus hainanensis (Rosaceae)
Authors: Yu Hui , Xia Nian‐He , Ye Hua‐Gu
Published: October 2008

The name Prunushainanensis (G. A. Fu & Y. S. Lin) W. C. Chen is invalid because only the basionym was cited and without reference. According to the Art. 32.4 of ICBN, Prunus hainanensis (G. A. Fu et Y. S. Lin) H. Yu, N. H. Xia & H. G. Ye is the correct name. This new combination is proposed herein.