bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relative Sensitivity of Two Bunchgrass Species to Fire
Authors: Robberecht R , Defosse GE
Published: October 2005

The response of two bunchgrass species, Festuca idahoensis and Agropyron spicatum, to fire was examined under three levels of fire severity. The fire treatment was applied with an instrument system that allowed precise control over the intensity and duration of fire, and full documentation of the temperatures experienced in various regions of each plant during the fire and postfire cooling phases. A quantitative index of fire exposure, or severity, for each plant was obtained by integrating the temperature curve for the meristematic crown region over the fire and postfire cooling periods. No significant plant mortality was observed at any fire severity level. Although tissue damage in newly initiated culms was observed for Festuca, this did not significantly affect culm or biomass productivity. Culm production was initiated earlier and more rapidly in Festuca than Agropyron, and within 60 days after fire exposure the total number of culms produced in Festuca was nearly that of unburned plants. Above ground biomass for both species was significantly less than that of unburned plants at the end of this 60-day period. Agropyron exhibited significantly less culm and biomass production at a moderate fire severity, whereas high fire severity was required for this reduction in Festuca. Contrary to previous studies, Festuca thus appears less sensitive to fire injury than Agropyron.
Slope and Fuel Load Effects on Fire Behavior: Laboratory Experiments in Pine Needles Fuel Beds
Authors: Dupuy JL
Published: October 2005

Laboratory fire experiments were conducted in both Pinus pinaster and Pinus halepensis litters in order to investigate the effect of slope on fire behaviour for different levels of fuel load. Simulated slopes ranged between -30 degrees and +30 degrees. The results are reported in terms of rate of spread and rate of mass loss when observed fire was quasi-steady. Upslope fires were observed, on the present devices, to be unsteady, and their flame to be three-dimensionnal, when slope and fuel load exceeded certain limits. The heat transfers involved in the explanation of the observed behaviours are discussed, especially on the base of the quite different results obtained in the two tested fuel. beds.
The Missing Tail and Other Considerations for the Use of Fire History Models
Authors: Finney MA
Published: October 2005

This paper reviews methods used for testing the fit of the cumulative form of a negative exponential distribution to the cumulative distribution of forest age-classes. It is shown that existing methods can lead to a greater chance of falsely rejecting the fit of the negative exponential model and inferring that fire frequencies have changed through time. This results when the old-age tail of a negative exponential distribution is mathematically assumed to be present at the end of the age-class distribution. In reality, the tail is censored from sample distributions of forest age-classes. Censoring alters the shape of a cumulative age-class distribution from the straight line expected for a semi-log graph of the cumulative negative exponential model. A solution to this problem is proposed that restricts the tests-of-fit to the portion of the negative exponential distribution that overlaps with the data to be tested. The cumulative age-class distribution can then be compared directly with the cumulative of a truncated negative exponential distribution. Considerations for interpreting a poor fit are then discussed.
A Comparison of Water Additives for Mopping-up After Forest Fires
Authors: Rawet D , Smith R , Kravainis G
Published: October 2005

A trial was carried out to compare the effectiveness of six extinguishants currently used in forest fire mopping up operations by the Western Australian Department of Conservation and Land Management. The extinguishants; water alone, water with retardant, foam, retardant plus foam, wetting agent and retardant plus wetting agent were compared by applying them to burning heaps of dry pine logs. There were twelve replicates of each extinguishant treatment, with one of each type being applied each day over twelve days. Foam, used alone or with retardant, was most effective in extinguishing flaming combustion, both in terms of the time taken and the amount of water used, but was least effective in preventing the re-ignition of hot, smouldering logs. Retardant plus foam required significantly less total water than the other extinguishants because of the effect of the retardant in delaying re-ignition. In terms of total water used the most expensive treatment was straight water, requiring 17% more than retardant plus foam but only about 7% more than the other four treatments. The poor performance of the foam treatments in preventing re-ignitions, may have been due to the method of application. The observed advantage of foam in terms of knockdown capability needs further validation.
Postfire Effects on Soil Properties and Nutrient Losses
Authors: Andreu V , Rubio JL , Forteza J , Cerni R
Published: October 2005

The effects of an August, 1992, wildfire on nutrient losses by water erosion have been studied. The fire affected an area of 9498 ha of pine forest and shrub, located in Sierra Calderona (Valencia, Spain). In the burned area, six stations of erosion measurement were set up immediately after the end of the fire. The results obtained in these stations are reported. Topographical, edaphological and vegetation characteristics of each station are described. Fourteen episodes of erosive rain with production of runoff and sediments, between August,1992, and November, 1993, were studied, mainly in relation to changes in the soil chemical characteristics. Data show that the highest soil and nutrient losses were produced in the period immediately after the fire. However, fire intensity is the factor that determines the soil status with respect to its response to nutrient losses.
Effects of Heating on the Microbial Populations of a Grassland Soil
Authors: Grasso GM , Ripabelli G , Sammarco ML , Mazzoleni S
Published: October 2005

Effects of burning on soil bacteria were studied under laboratory conditions on grassland soil samples. Low intensity fire conditions were simulated in a muffle furnace (temperature of 450°C for 3 min). The number of aerobic heterotrophic bacteria and sporeformers was studied in heated and unheated samples. Immediately after burning, the number of bacteria decreased; an increase resulted however after 24 hours and after 10 days. Thirty days after treatment the number of bacteria decreased again in the treated samples, achieving values similar to the unburned soil. The laboratory procedure presented in the paper seems to be a useful approach to simulate field conditions where fire experiments are difficult to manage.
Vegetation Composition in a Post-Fire Successional Gradient of Pinus Halepensis Forests in Attica, Greece
Authors: Kazanis D , Arianoutsou M
Published: October 2005

The vegetation composition of a post-fire succession in Aleppo pine forests of Attica, Greece, was studied by a synchronic method. The sites form a post-fire chronosequence and have typical Mediterranean climate. Data on the flora of the burned sites, growth and life forms of the various plant taxa, as well as on vegetation structure are provided. The burned ecosystems recovered quite rapidly. During the first four years of the post-fire succession, herbaceous taxa dominate the flora of the forests, peaking at the second year. After 15 years little change in the vegetation was observed. The richest family in terms of the number of taxa was the Leguminosae, especially in the two first years of succession. Most of these taxa were herbaceous. The relative contribution of legumes to the flora after two years is gradually restricted.
Fire History in Interior Ponderosa Pine Communities of the Black Hills, South Dakota, USA
Authors: Brown PM , Sieg CH
Published: October 2005

Chronologies of fire events were reconstructed from crossdated fire-scarred ponderosa pine trees for four sites in the south-central Black Hills. Compared to other ponderosa pine forests in the southwest US or southern Rocky Mountains, these communities burned less frequently. For all sites combined, and using all fires detected, the mean fire interval (MFI), or number of years between fire years, was 16 years (± 14 SD) for the period 1388 to 1900. When a yearly minimum percentage of trees recording scars of ≥ 25% is imposed, the MFI was 20 years (± 14 SD). The length of the most recent fire-free period (104 years, from 1890 to 1994) exceeds the longest intervals in the pre-settlement era (before ca. 1874), and is likely the result of human-induced land use changes. Based on fire scar position within annual rings, most past fires occurred late in the growing season or after growth had ceased for the year. These findings have important implications for management of ponderosa pine forests in the Black Hills and for understanding the role of fire in pre-settlement ecosystem function.
Towards Automated Fire Monitoring From Space: Semi-Automated Mapping of the January 1994 New South Wales Wildfires Using AVHRR Data.
Authors: Harris AJL
Published: October 2005

The Advanced Very High Resolution Radiometer (AVHRR) is capable of providing low cost thermal data in which wild-fires can easily be detected. Data are available for large areas (~ 3000 x 6000 km) at-least 4 times a day, and can be received directly by the user. An automated hot-spot detection technique inserted into the data stream could therefore provide timely fire information for wild-fire monitoring. Such an automated technique is applied to AVHRR data acquired for the wild-fires which burnt extensive areas in New South Wales, Australia, during January 1994. The technique allows rapid production of fire maps. These revealed a number of major fires burning mainly within the National Parks, impacting on settlements and roads. Such a synoptic view of these fire events would be difficult to obtain using any other means.
Physical Properties of Woody Fuel Particles of Sierra Nevada Conifers
Authors: Van Wagdendonk JW , Benedict JM , Sydoriak WM
Published: October 2005

A study of the physical properties of Sierra Nevada conifer fuel particles showed that average diameter, squared quadratic mean diameter, surface-area-to-volume ratio, and specific gravity varied significantly by species for all four timelag fuel diameter size classes. The nonhorizontal angle was not significantly affected by size class, and the developmental stage of the overstory did not affect any of the properties. These values are used to calculate fuel weight and predict fire behavior. Regional variation in physical properties can result in fuel weight estimates for the Sierra Nevada that differ from under 40.8 percent to over 8.3 percent from those calculated from Rocky Mountain values. These differences made small changes in predicted fire behavior.
Influence of Simulated Burning of Soil-Litter From Low Sagebrush, Squirreltail, Cheatgrass, and Medusahead on Water-Soluble Anions and Cations
Authors: Blank RR , Allen FL , Young JA
Published: October 2005

We evaluated the influence of temperature and heating time on water-soluble anions and cations of soil-litters of low sagebrush (Artemisia arbuscula ssp. longicaulis), squirreltail (Elymus elymoides), cheatgrass (Bromus tectorum), and medusahead (Taeniatherum caputmeduase ssp. asperum). Soil-litters were collected from volcanic tablelands north of Honey Lake, California. These high clay, montmorillonitic, soils have rarely experienced wildfires. Soil-litter samples, in a 50 mt crucible, were placed in a preheated muffle furnace using a time-temperature matrix of 150, 250, 350, and 450°C at 1, 5,and 15 min. High performance ion-exchange chromatography was used to quantify water-soluble cations and anions. For most measured solutes, there was either a significant (P less than or equal to 0.05) burn time × temperature or a significant burn time × temperature × soil-litter type interaction. As compared to pre-burn values, heating of soil generally increased the concentration of the water-soluble solutes measured; nitrate was the exception. Maximum solute values were generally obtained at a temperature of 350°C at 5 and 15 min heating time. A temperature of 450°C at 15 min heating time resulted in the significant reduction of solute concentration below the maximum values. Nitrate was significantly higher in squirreltail soil-litter than the other soil-litters when the burn time was 1 min. Heating, in general, fostered an increase in water-soluble ammonium. For most solutes, heat-induced increases were greatest for the low sagebrush soil-litter.
Determining the age of adult wild dogs (Canis lupus dingo, C. l. domesticus and their hybrids). I. Pulp cavity:tooth width ratios
Authors: Kershaw Kristan , Allen Lee , Lisle Allan , Withers Kerry
Published: October 2005

In order to determine the age of adult wild dogs, we compared two methods (that of Thomson and Rose (TR method) and that of Knowlton and Whittemore (KW method)) of measuring and calculating pulp cavity : tooth width ratios on upper and lower canine teeth from 68 mixed-sex, known-age wild dogs of 9 months to 13 years of age reared at two localities. Although significant relationships (P = 0.0001) were found between age and pulp cavity ratios by both methods, the TR ratio calculation and measurement showed heteroscedasity in error variance whereas the KW ratios had a more stable error variance and were normally distributed. The KW method also found significant differences between pulp cavity ratios between teeth of the upper and lower jaws (P < 0.0001) and sex (P = 0.01) but not geographic origin (P = 0.1). Regressions and formulae for fitted curves are presented separately for male and female wild dogs. Males show greater variability in pulp cavity decrements with age than do females, suggesting a physiological difference between the sexes. We conclude that the KW method of using pulp cavity as a proportion of tooth width, measured 15 mm from the root tip and averaged over both upper canines, is the more accurate method of estimating the age of adult wild dogs.
Comparative phylogenomics of the food-borne pathogen
Campylobacter jejuni
reveals genetic markers predictive of infection source
Authors: Champion Olivia L. , Gaunt Michael W. , Gundogdu Ozan , Elmi Abdi , Witney Adam A. , Hinds Jason , Dorrell Nick , Wren Brendan W.
Published: October 2005

Campylobacter jejuni
is the predominant cause of bacterial gastroenteritis worldwide, but traditional typing methods are unable to discriminate strains from different sources that cause disease in humans. We report the use of genomotyping (whole-genome comparisons of microbes using DNA microarrays) combined with Bayesian-based algorithms to model the phylogeny of this major food-borne pathogen. In this study 111
C. jejuni
strains were examined by genomotyping isolates from humans with a spectrum of
C. jejuni
-associated disease (70 strains), chickens (17 strains), bovines (13 strains), ovines (5 strains), and the environment (6 strains). From these data, the Bayesian phylogeny of the isolates revealed two distinct clades unequivocally supported by Bayesian probabilities (
P
= 1); a livestock clade comprising 31/35 (88.6%) of the livestock isolates and a “nonlivestock” clade comprising further clades of environmental isolates. Several genes were identified as characteristic of strains in the livestock clade. The most prominent was a cluster of six genes (
cj1321
to
cj1326
) within the flagellin glycosylation locus, which were confirmed by PCR analysis as genetic markers in six additional chicken-associated strains. Surprisingly these studies show that the majority (39/70, 55.7%) of
C. jejuni
human isolates were found in the nonlivestock clade, suggesting that most
C. jejuni
infections may be from nonlivestock (and possibly nonagricultural) sources. This study has provided insight into a previously unidentified reservoir of
C. jejuni
infection that may have implications in disease-control strategies. The comparative phylogenomics approach described provides a robust methodological prototype that should be applicable to other microbes.
RETRACTED: Complete and persistent phenotypic correction of phenylketonuria in mice by site-specific genome integration of murine phenylalanine hydroxylase cDNA
Authors: Chen Li , Woo Savio L. C.
Published: October 2005

We explored the potential of using a bacteriophage integrase system to achieve site-specific genome integration of murine phenylalanine hydroxylase cDNA in the livers of phenylketonuric (PKU) mice. The phiBT1 phage integrase is an enzyme that catalyses the efficient recombination between unique sequences in the phage and bacterial genomes, leading to the site-specific integration of the former into the latter in a unidirectional manner. Here we showed that this phage integrase functions efficiently in mouse cells, and several naturally occurring pseudo-attP sites located in the intergenic regions of the mouse genome have been identified and molecularly characterized. We further demonstrated that the addition of nuclear localization signal sequences to the C terminus of the phage integrase enhanced the efficiency for transgene integration into the mouse genome. Using this phage integration system, we delivered mouse phenylalanine hydroxylase cDNA to the livers of PKU mice by hydrodynamic injection of plasmid DNA and showed that the severity of the hyperphenylalaninemic phenotype in the treated mice decreased significantly. After three applications, serum phenylalanine levels in all treated PKU mice were reduced to the normal range and remained stable thereafter. Their fur color also changed from gray to black, indicating the reconstitution of melanin biosynthesis as a result of available tyrosine derived from reconstituted phenylalanine hydroxylation in the liver. Thus, the phiBT1 bacteriophage integrase represents an effective site-specific genome integration system in mammalian cells and can be of great value in DNA-mediated gene therapy for a multitude of genetic disorders.
Molecular signatures for sex in the Placozoa
Authors: Signorovitch Ana Y. , Dellaporta Stephen L. , Buss Leo W.
Published: October 2005

Placozoans, the simplest free-living animals, have never been observed to reproduce sexually. Here, we describe molecular evidence for sexual reproduction within one clade of the Placozoa. In a population sample of 10 individuals, within-individual and overall nucleotide diversity were similar to each other and consistent with levels observed in sexually reproducing species. Intergenic recombination as well as the sharing of alleles between heterozygous and homozygous individuals was also observed. These hallmarks of sexual reproduction establish that sex is indeed present in this phylum.
The discovery of ubiquitin-dependent proteolysis
Authors: Wilkinson Keith D.
Published: October 2005

In early 1980, Irwin A. Rose, Avram Hershko, and Aaron Ciechanover published two papers in PNAS that reported the astounding observation that energy-dependent intracellular proteolysis was far more complicated than the previously accepted models of lysosomal proteolysis or the action of ATP-dependent proteases such as bacterial lon. In fact, it has turned out to be even more complicated than they could have suspected. The general model of covalently attaching a small protein as a targeting signal has proved to be every bit as important to eukaryotic cells as the better understood modifications such as phosphorylation or acetylation. The key player in this modification, a small protein called ubiquitin (APF-1 in these papers), is the founding member of a large family of proteins containing the β-grasp fold and is used as a posttranslational targeting signal to modify the structure, function, and/or localization of other proteins. The story of this discovery is a textbook example of the confluence of intellectual curiosity, unselfish collaboration, chance, luck, and preparation.
A conserved motif in transmembrane helix 1 of diphtheria toxin mediates catalytic domain delivery to the cytosol
Authors: Ratts Ryan , Trujillo Carolina , Bharti Ajit , vanderSpek Johanna , Harrison Robert , Murphy John R.
Published: October 2005

A 10-aa motif in transmembrane helix 1 of diphtheria toxin that is conserved in anthrax edema factor, anthrax lethal factor, and botulinum neurotoxin serotypes A, C, and D was identified by
blast
,
clustal w
, and
meme
computational analysis. Using the diphtheria toxin-related fusion protein toxin DAB
389
IL-2, we demonstrate that introduction of the L221E mutation into a highly conserved residue within this motif results in a nontoxic catalytic domain translocation deficient phenotype. To further probe the function of this motif in the process by which the catalytic domain is delivered from the lumen of early endosomes to the cytosol, we constructed a gene encoding a portion of diphtheria toxin transmembrane helix 1, T1, which carries the motif and is expressed from a CMV promoter. We then isolated stable transfectants of Hut102/6TG cells that express the T1 peptide, Hut102/6TG-T1. In contrast to the parental cell line, Hut102/6TG-T1 cells are
ca.
10
4
-fold more resistant to the fusion protein toxin. This resistance is completely reversed by coexpression of small interfering RNA directed against the gene encoding the T1 peptide in Hut102/6TG-T1 cells. We further demonstrate by GST-DT140-271 pull-down experiments in the presence and absence of synthetic T1 peptides the specific binding of coatomer protein complex subunit β to this region of the diphtheria toxin transmembrane domain.
The changing demographic, legal, and technological contexts of political representation
Authors: Forest Benjamin
Published: October 2005

Three developments have created challenges for political representation in the U.S. and particularly for the use of territorially based representation (election by district). First, the demographic complexity of the U.S. population has grown both in absolute terms and in terms of residential patterns. Second, legal developments since the 1960s have recognized an increasing number of groups as eligible for voting rights protection. Third, the growing technical capacities of computer technology, particularly Geographic Information Systems, have allowed political parties and other organizations to create election districts with increasingly precise political and demographic characteristics. Scholars have made considerable progress in measuring and evaluating the racial and partisan biases of districting plans, and some states have tried to use Geographic Information Systems technology to produce more representative districts. However, case studies of Texas and Arizona illustrate that such analytic and technical advances have not overcome the basic contradictions that underlie the American system of territorial political representation.
Human decidual NK cells form immature activating synapses and are not cytotoxic
Authors: Kopcow Hernan D. , Allan David S. J. , Chen Xi , Rybalov Basya , Andzelm Milena M. , Ge Baoxue , Strominger Jack L.
Published: October 2005

In early pregnancy invading fetal trophoblasts encounter abundant maternal decidual natural killer cells (dNK). dNK express perforin, granzymes A and B and the activating receptors NKp30, NKp44, NKp46, NKG2D, and 2B4 as well as LFA-1. Even though they are granular and express the essential molecules required for lysis, fresh dNK displayed very reduced lytic activity on classical MHC I negative targets K562 and 721.221, ≈15% of that of peripheral NK cells. dNK formed conjugates and activating immune synapses with 721.221 and K562 cells in which CD2, LFA-1 and actin were polarized toward the contact site. However, in contrast to peripheral NK cells, they failed to polarize their microtubule organizing centers and perforin-containing granules to the synapse, accounting for their lack of cytotoxicity.
Insulin-like growth factors 1 and 2 induce lymphangiogenesis
in vivo
Authors: Björndahl Meit , Cao Renhai , Nissen L. Johan , Clasper Steve , Johnson Louise A. , Xue Yuan , Zhou Zhongjun , Jackson David , Jon Hansen Anker , Cao Yihai
Published: October 2005

Lymphangiogenesis is an important process that contributes to the spread of cancer. Here we show that insulin-like growth factors 1 (IGF-1) and 2 (IGF-2) induce lymphangiogenesis
in vivo
. In a mouse cornea assay, IGF-1 and IGF-2 induce lymphangiogenesis as detected with LYVE-1, a specific marker for lymphatic endothelium. Interestingly, IGF-1-induced lymphangiogenesis could not be blocked by a soluble vascular endothelial growth factor receptor 3, suggesting that the vascular endothelial growth factor receptor 3-signaling pathway is not required for IGF-induced lymphangiogenesis.
In vitro
, IGF-1 and IGF-2 significantly stimulated proliferation and migration of primary lymphatic endothelial cells. IGF-1 and IGF-2 induced phosphorylation of intracellular signaling components, such as Akt, Src, and extracellular signal-regulated kinase in lymphatic endothelial cells. Immunohistochemistry, RT-PCR, and Affymetrix GeneChip microarray analysis showed that the receptors for IGFs are present in lymphatic endothelium. Together, our findings suggest that IGFs might act as direct lymphangiogenic factors, although any indirect roles in the induction of lymphangiogenesis cannot be excluded. Because members of the IGF ligand and receptor families are widely expressed in various types of solid tumors, our findings suggest that these factors are likely to contribute to lymphatic metastasis.
Spatial and temporal regulation of cofilin activity by LIM kinase and Slingshot is critical for directional cell migration
Authors: Nishita Michiru , Tomizawa Chinatsu , Yamamoto Masahiro , Horita Yuji , Ohashi Kazumasa , Mizuno Kensaku
Published: October 2005

Cofilin mediates lamellipodium extension and polarized cell migration by accelerating actin filament dynamics at the leading edge of migrating cells. Cofilin is inactivated by LIM kinase (LIMK)–1-mediated phosphorylation and is reactivated by cofilin phosphatase Slingshot (SSH)-1L. In this study, we show that cofilin activity is temporally and spatially regulated by LIMK1 and SSH1L in chemokine-stimulated Jurkat T cells. The knockdown of LIMK1 suppressed chemokine-induced lamellipodium formation and cell migration, whereas SSH1L knockdown produced and retained multiple lamellipodial protrusions around the cell after cell stimulation and impaired directional cell migration. Our results indicate that LIMK1 is required for cell migration by stimulating lamellipodium formation in the initial stages of cell response and that SSH1L is crucially involved in directional cell migration by restricting the membrane protrusion to one direction and locally stimulating cofilin activity in the lamellipodium in the front of the migrating cell. We propose that LIMK1- and SSH1L-mediated spatiotemporal regulation of cofilin activity is critical for chemokine-induced polarized lamellipodium formation and directional cell movement.
A telomeric repeat sequence adjacent to a DNA double-stranded break produces an anticheckpoint
Authors: Michelson Rhett J. , Rosenstein Saul , Weinert Ted
Published: October 2005

Telomeres are complex structures that serve to protect chromosome ends. Here we provide evidence that in Saccharomyces cerevisiae telomeres may contain an anticheckpoint activity that prevents chromosome ends from signaling cell cycle arrest. We found that an internal tract of telomeric repeats inhibited DNA damage checkpoint signaling from adjacent double-strand breaks (DSBs); cell cycle arrest lasted 8-12 h from a normal DSB, whereas it lasted only 1-2 h from a DSB adjacent to a telomeric repeat. The shortened or abridged arrest was not the result of DNA repair, nor reduced amounts of single-stranded DNA, nor of adaptation. The molecular identity of this telomere repeat-associated anticheckpoint activity is unknown, though it is not dependent upon telomerase or telomere-proximal gene silencing. The anticheckpoint may inhibit the ATR yeast ortholog Mec1 because Rad9 and Rad53 became dephosphorylated and inactivated during the abridged arrest. The anticheckpoint acts regionally; it inhibited signaling from DNA breaks up to 0.6 kb away from the telomeric repeat but not from a DSB present on a separate chromosome. We propose that after formation of the DSB near the telomeric repeat, a mature telomere forms in 1-2 h, and the telomere then contains proteins that inhibit checkpoint signaling from nearby DNA breaks.
A histone code in meiosis: the histone kinase, NHK-1, is required for proper chromosomal architecture in Drosophila oocytes
Authors: Ivanovska Irena , Khandan Tulasi , Ito Takashi , Orr-Weaver Terry L.
Published: October 2005

To promote faithful propagation of the genetic material during sexual reproduction, meiotic chromosomes undergo specialized morphological changes that ensure accurate segregation of homologous chromosomes. The molecular mechanisms that establish the meiotic chromosomal structures are largely unknown. We describe a mutation in a recently identified Histone H2A kinase, nhk-1, in Drosophila that leads to female sterility due to defects in the formation of the meiotic chromosomal structures. The metaphase I arrest and the karyosome, a critical prophase I chromosomal structure, require nucleosomal histone kinase-1 (NHK-1) function. The defects are a result of failure to disassemble the synaptonemal complex and to load condensin onto the mutant chromosomes. Embryos laid by nhk-1-/- mutant females arrest with aberrant polar bodies and mitotic spindles, revealing that mitosis is affected as well. We analyzed the role of Histone H2A phosphorylation with respect to the histone code hypothesis and found that it is required for acetylation of Histone H3 and Histone H4 in meiosis. These studies reveal a critical role for histone modifications in chromosome dynamics in meiosis and mitosis.
Bem1p, a scaffold signaling protein, mediates cyclin-dependent control of vacuolar homeostasis in Saccharomyces cerevisiae
Authors: Han Bong-Kwan , Bogomolnaya Lydia M. , Totten James M. , Blank Heidi M. , Dangott Lawrence J. , Polymenis Michael
Published: October 2005

How proliferating cells maintain the copy number and overall size of their organelles is not clear. We had previously reported that in the budding yeast Saccharomyces cerevisiae the G1 cyclin Cln3p is required for vacuolar (lysosomal) homotypic fusion and loss of Cln3p leads to vacuolar fragmentation. The Cdc42p GTPase is also required for vacuole fusion. Here we show that the scaffold protein Bem1p, a critical regulator of Cdc42p activity, is a downstream effector of Cln3p and the cyclin-dependent kinase (Cdk) Cdc28p. Our results suggest that Bem1p is phosphorylated in a Cdk-dependent manner to promote vacuole fusion. Replacing Ser72 with Asp, to mimic phosphorylation at an optimal Cdk-consensus site located in the first SH3 domain of Bem1p, suppressed vacuolar fragmentation in cells lacking Cln3p. Using in vivo and in vitro assays, we found that Cln3p was unable to promote vacuole fusion in the absence of Bem1p or in the presence of a nonphosphorylatable Bem1p-Ser72Ala mutant. Furthermore, activation of Cdc42p also suppressed vacuolar fragmentation in the absence of Cln3p. Our results provide a mechanism that links cyclin-dependent kinase activity with vacuole fusion through Bem1p and the Cdc42p GTPase cycle.
The potential interactions between polyunsaturated fatty acids and colonic inflammatory processes
Authors: Mills S C , Windsor A C , Knight S C
Published: October 2005

n-3 Polyunsaturated fatty acids (PUFAs) are recognized as having an anti-inflammatory effect, which is initiated and propagated via a number of mechanisms involving the cells of the immune system. These include: eicosanoid profiles, membrane fluidity and lipid rafts, signal transduction, gene expression and antigen presentation. The wide-range of mechanisms of action of n-3 PUFAs offer a number of potential therapeutic tools with which to treat inflammatory diseases. In this review we discuss the molecular, animal model and clinical evidence for manipulation of the immune profile by n-3 PUFAs with respect to inflammatory bowel disease. In addition to providing a potential therapy for inflammatory bowel disease there is also recent evidence that abnormalities in fatty acid profiles, both in the plasma phospholipid membrane and in perinodal adipose tissue, may be a key component in the multi-factorial aetiology of inflammatory bowel disease. Such abnormalities are likely to be the result of a genetic susceptibility to the changing ratios of n-3 : n-6 fatty acids in the western diet. Evidence that the fatty acid components of perinodal adipose are fuelling the pro- or anti-inflammatory bias of the immune response is also reviewed.
The costimulatory molecules CD80, CD86 and OX40L are up-regulated inAspergillus fumigatussensitized mice
Authors: Barrios C S , Johnson B D , D. Henderson J , Fink J N , Kelly K J , Kurup V P
Published: October 2005

Aspergillus fumigatus (Af) is a fungus associated with allergic bronchopulmonary aspergillosis (ABPA) and other allergic diseases. Immune responses in these diseases are due to T and B cell responses. T cell activation requires both Af-specific engagement of the T-cell-receptor as well as interaction of antigen independent costimulatory molecules including CD28-CD80/CD86 and OX40–OX40L interactions. Since these molecules and their interactions have been suggested to have a potential involvement in the pathogenesis of ABPA, we have investigated their role in a model of experimental allergic aspergillosis. BALB/c mice were primed and sensitized with Af allergens, with or without exogenous IL-4. Results showed up-regulation of both CD86 and CD80 molecules on lung B cells from Af-sensitized mice (79% CD86+ and 24% CD80+) and Af/rIL-4-treated mice (90% CD86+ and 24% CD80+) compared to normal controls (36% and 17%, respectively). Lung macrophages in Af-sensitized mice treated or not with IL-4 showed enhanced expression of these molecules. OX40L expression was also up-regulated on lung B cells and macrophages from both Af-sensitized and Af/rIL-4 exposed mice as compared to normal controls. All Af-sensitized animals showed peripheral blood eosinophilia, enhanced total serum IgE and allergen-specific IgG1 antibodies and characteristic lung inflammation. The up-regulation of CD80, CD86 and OX40L molecules on lung B cells and macrophages from Af-allergen exposed mice suggests a major role for these molecules in the amplification and persistence of immunological and inflammatory responses in ABPA.
Abrogation of IFN-γ mediated epithelial barrier disruption by serine protease inhibition
Authors: Willemsen L E M , Hoetjes J P , Van Deventer S J H , Van Tol E A F
Published: October 2005

The intestinal barrier function is often impaired in a variety of diseases including chronic inflammatory bowel disease. Increased intestinal permeability during episodes of active disease correlates with destruction or rearrangement of the tight junction protein complex. IFN-γ has been widely studied for its effect on barrier function and tight junction structures but its mode of action remains unclear. Since the claudin family of tight junction proteins is proposed to be involved in barrier maintenance we studied the effect of IFN-γ on claudin expression in relation to epithelial barrier function. Cycloheximide and protease inhibitors were used to study mechanisms of IFN-γ mediated barrier disruption. Intestinal epithelial cells were exposed to IFN-γ and permeability was evaluated by horse radish peroxidase (HRP) and 4 kD FITC-dextran fluxes. Occludin and claudin-1, -2, -3, and -4 tight junction protein expression was determined by Western blotting. Occludin and claudin-2 protein expression was dramatically reduced after IFN-γ exposure, which correlated with increased permeability for HRP and FITC-dextran. Interestingly, cleavage of claudin-2 was observed after incubation with IFN-γ. Serine protease inhibitor AEBSF completely abrogated IFN-γ mediated barrier disruption which was associated with preservation of claudin-2 expression. Moreover, IFN-γ induced loss of barrier integrity was found to affect claudin-2 and occludin expression through different mechanisms. Since inhibition of serine protease activity abrogates IFN-γ mediated barrier disruption this may be an important target for therapeutic intervention.
Chemokines in onchocerciasis patients after a single dose of ivermectin
Authors: Fendt J , Hamm D M , Banla M , Schulz-Key H , Wolf H , Helling-Giese G , Heuschkel C , Soboslay P T
Published: October 2005

Ivermectin treatment will effectively diminish microfilariae (Mf) of Onchocerca volvulus in the skin of patients, but therapy is associated with adverse host inflammatory responses. To investigate the association of proinflammatory chemokines with the intensity of infection and clinical adverse reactions, chemokine serum levels were measured in patients following ivermectin treatment (100 µg/kg, 150 µg/kg or 200 µg/kg) or placebo. The density of O. volvulus Mf per mg skin decreased by 85%, 97%, 97% and 90% at day 3, at month 3, month 6 and at 1 year post-ivermectin. The cutaneous T cell-attracting chemokine (CTACK/CCL27) was found highly elevated in onchocerciasis patients compared to infection-free European controls (P = 0·0004) and it did not change following ivermectin or placebo to 1 year post-therapy. The chemokine RANTES/CCL5 (regulated on activated and normally T cell-expressed) was similarly high in onchocerciasis patients and infection-free European controls; the RANTES/CCL5 levels did not change following treatment until 6 months post-therapy but were slightly elevated at 1 year post-therapy (P < 0·02). In contrast, the Th2-type chemoattractants, thymus and activation regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22), were activated at 3 days post-ivermectin (P < 0·0001) to return to pretreatment or lower levels thereafter. The Th1-type chemoattractants, macrophage inflammatory protein (MIP)-1α/CCL3 and MIP-1β/CCL4 were low before ivermectin treatment, but following clearance of microfilariae of O. volvulus their levels increased from 6 months post-therapy onwards (for both at 12 months post-therapy, P < 0·0001). The adverse reaction scores (RS) in treated patients increased significantly on day 3 (P < 0·02) while it remained unchanged in those who received placebo (P = 0·22); RS interacted with the microfilarial density (P = 0·01), but not with the dose of ivermectin or with the serum levels of MIP-1α/CCL3, MIP-1β/CCL4, TARC/CCL17, MDC/CCL22 and CTACK/CCL27. Our observations suggest that following ivermectin, macrophages as well as memory Th2-type lymphocytes and B cells, attracted and activated by MDC/CCL22, TARC/CCL17 and CTACK/CCL27, may contribute to dermal immune responses and O. volvulus Mf killing and clearance. The transient changes of TARC/CCL17 and MDC/CCL22 were not associated with clinical adverse responses, and the later rise of MIP-1α/CCL3 and MIP-1β/CCL4 showed a reactivation of Type 1 immune responses associated with persistent low levels of O. volvulus microfilariae and an expiring O. volvulus infection.
The immune responses to human and microbial heat shock proteins in periodontal disease with and without coronary heart disease
Authors: Hasan A , Sadoh D , Palmer R , Foo M , Marber M , Lehner T
Published: October 2005

The human 60 kDa and microbial 65 kDa heat shock proteins (HSP) have been implicated in the pathogenesis of chronic periodontitis (P) and coronary heart disease (CHD). We have studied four male non-smoking cohorts of 81 subjects, matched for age. Group (a) consisted of a healthy group with minimal gingivitis (n = 18), group (b) were patients with P (n = 23), group (c) patients with CHD and minimal gingivitis (n = 20) and group (d) patients with CHD and P (n = 20). T cells separated from peripheral blood were found to be primed to both microbial HSP65 and human HSP60 but significant CD4, human leucocyte antigen (HLA) class II-restricted proliferative responses were found only with the human HSP60 in patients with P (P < 0·001) and CHD without (P < 0·001) or with (P < 0·00001) periodontitis. Dose-dependent inhibition of T cell proliferative responses was carried out to determine the receptors involved in recognition of HSP60 and HSP65. Monoclonal antibodies to CD14 showed inhibition of T cell proliferation stimulated by both HSP60 and HSP65, consistent with the role of CD14 as a receptor for these HSPs in P and CHD. The toll-like receptor 2 (TLR-) and TLR-4 were then studied and these showed that TLR-4 was recognized by microbial HSP65, whereas TLR-2 was recognised by human HSP60 in both P and CHD. However, a dissociation was found in the HSP60 and TLR4 interaction, as TLR4 appeared to have been recognized by HSP60 in P but not in CHD. The results suggest an autoimmune or cross-reactive CD4+ class II-restricted T cell response to the human HSP60 in P and CHD. Further studies are required to determine if there is a common epitope within HSP60 that stimulates T cell proliferation in P and CHD.
Sexual medicine in the medical curriculum
Authors: WAGNER G.
Published: October 2005

The new field of Sexual Medicine has now changed to the primary care physician because of the new symptom‐treating pharmacological possibilities, a fact not to be foreseen 10 years ago. The future, therefore, is to create the platform for the ‘basic doctor’ to identify and correctly treat male and female sexual dysfunction on the basis of a sufficient knowledge (obtained through formalized, pre‐graduate education) within the field of Sexual Medicine. All this will need positive support and good strategies, as well as evidence‐based new knowledge created by endocrinology, gynaecology, andrology, genetics, neurology, angiology, but also psychology, sociology, anthropology and related disciplines to help the medical clinician to fulfil his Hippocratic Oath: to assist the individual who needs help – in sexual dilemmas as well.
Why humans need type 5 phosphodiesterase inhibitors
Authors: CELLERINO A. , JANNINI E. A.
Published: October 2005

Erectile dysfunction (ED) is a widespread medical condition affecting millions of males at any age and requiring medical treatment. ED may simply reflect a limit of human physiology, yet ED equates to genetic death and the high prevalence of ED is a clear evolutionary paradox. Why is a condition which totally blocks reproduction so widespread? Epidemiology shows that impotence is a common symptom of almost all major diseases and male reproductive physiology is sensitive to general health and to environmental, psychological, and physical stressors. Moreover, erectile dysfunction is a predictor of myocardial infarction and stroke. Briefly, efficient erection is a marker of good health and good health prognosis. In the animal kingdom, mate choice is often based on extravagant and cumbersome physical traits (such as the peacock's tail). These traits, that are necessary for gene propagation, are at the same time efficient handicaps which reduce the survival of the carrier. What animal studies show, is that these handicaps can function as honest indicators of the individual's fitness. In other words, their expression is condition‐dependent and only individuals with high phenotypic quality present the trait. By mating with males which express the trait, females indirectly select for individuals of superior fitness which will be inherited by the offspring. Erection is very clearly a condition‐dependent trait in the human species. We suggest that the fragility of male sexual physiology is a sexually selected handicap which hampers the reproduction of individuals with lower phenotypic quality.
Central hormonal regulation and dimorphism of arousal
Authors: BENVENGA S.
Published: October 2005

From studies in animals, we have learned that differences in sexual behaviour between males and females reflect anatomical and biochemical differences between the male and female brain. A masculine behaviour (and therefore a masculine brain) results from the biological effect on the developing brain exerted by testosterone, which is secreted by the gonads and aromatized into oestrogens in the brain. However, congenital disorders of the androgen as well as oestrogen signalling in human males have failed to show any appreciable derangement in sexual behaviour. Based on other evidence in animals, sexual differences in brain (and behaviour) are not hormonally triggered but genetically determined. This other theory states that sexual behaviour is determined by the chromosomal sex existing in cells, including brain cells. A number of excitatory and inhibitory signals modulate the activity of certain brain structures. Scientists have begun to test some of these chemicals or their synthetic analogues/antagonists in humans.
Vascular aetiology of erectile dysfunction
Authors: FRANCAVILLA S. , BOCCHIO M. , PELLICCIONE F. , NECOZIONE S. , FRANCAVILLA F.
Published: October 2005

Erectile dysfunction (ED) shares the same vascular risk factors (VRFs) with coronary arteries disease (CAD). A reduced biological activity of endothelium‐derived nitric oxide links human atherosclerosis to ED and underscores the role of an altered endothelium in the pathogenesis of both conditions. ED is associated to a systemic endothelial cell activation/dysfunction independent from VRFs or from a diffuse vascular damage, indicating that ED is a marker of an early systemic endothelial damage, a relevant determinant of atherosclerosis. A diffuse vascular damage of carotid arteries indicative of pre‐clinical atherosclerosis is significantly associated to an increased risk of severe ED in men with VRFs but without clinical atherosclerosis and ED was the most efficient predictor of angiographically verified silent CAD among different VRFs in uncomplicated type 2 diabetes. In conclusion, ED may be the only clinical correlate of a diffuse, unrecognized vascular damage that is associated to a documented future risk of acute vascular events. Searching ED might be of relevance in men with VRFs but no other clinical atherosclerosis to identify patients that should aggressively reduce their VRFs while treating ED.
Diagnosing erectile dysfunction: instruments for endocrine diagnosis
Authors: LOMBARDO F. , GANDINI L. , JANNINI E. A. , SGRÒ P. , GILIO B. , TOSELLI L. , DONDERO F. , LENZI A.
Published: October 2005

Endocrine factors represent an important and potentially treatable cause of sexual dysfunction. The availability of a correct endocrinological diagnosis allows correct identification of most cases of sexual dysfunction in which the endocrine apparatus is involved. Not only the most frequent causes of endocrine sexual dysfunction, such as hypogonadism and hyperprolactinaemia, but almost all extra‐gonadal endocrinopathies (hyper‐and hypothyroidism, hyper‐ and hypocortisolism, steroidal secreting tumours, etc.) may have importance to a greater or lesser extent in sexual function. It is, therefore, necessary that the diagnostic process for sexual dysfunctions of an endocrine nature be as integrated and wide as possible, especially as such pathologies are normally extremely responsive to medical or surgical therapy.
Diagnosing Erectile Dysfunction: flow‐chart
Authors: FORESTA C. , CARETTA N. , PALEGO P. , SELICE R. , GAROLLA A. , FERLIN A.
Published: October 2005

Erectile dysfunction (ED) has been defined by the National Institute of Health (NIH) as the inability to achieve and/or maintain an erection for a satisfactory sexual intercourse. Discordant data have been reported on ED epidemiology with prevalence ranging from 12% to 52%. A recent study reported an ED prevalence of 12.8% in Italy. ED is a symptom, sometimes the first, of different internal diseases. ED can mark the point where evaluation and prevention of important diseases (such as diabetes, arterial hypertension, atherosclerosis) hitherto unknown by the patients, can begin. The andrologist's cultural baggage must include the ability to identify the pathology that can determine ED and the capacity to programme a specific diagnostic workup.