bluuebunny/crossref_metadata_2025 huggingface dataset:
Enzymatic activity of the SARS coronavirus main proteinase dimer
Authors: Graziano Vito , McGrath William J. , DeGruccio Ann Marie , Dunn John J. , Mangel Walter F.
Published: April 2006

The enzymatic activity of the SARS coronavirus main proteinase dimer was characterized by a sensitive, quantitative assay. The new, fluorogenic substrate, (Ala‐Arg‐Leu‐Gln‐NH)2‐Rhodamine, contained a severe acute respiratory syndrome coronavirus (SARS CoV) main proteinase consensus cleavage sequence and Rhodamine 110, one of the most detectable compounds known, as the reporter group. The gene for the enzyme was cloned in the absence of purification tags, expressed in Escherichia coli and the enzyme purified. Enzyme activity from the SARS CoV main proteinase dimer could readily be detected at low pM concentrations. The enzyme exhibited a high K
m, and is unusually sensitive to ionic strength and reducing agents.
A translational enhancer element on the 3′‐proximal end of the Panicum mosaic virus genome
Authors: Batten Jeffrey S. , Desvoyes Benedicte , Yamamura Yoshimi , Scholthof Karen-Beth G.
Published: April 2006

Panicum mosaic virus (PMV) is a single‐stranded positive‐sense RNA virus in the family Tombusviridae. PMV genomic RNA (gRNA) and subgenomic RNA (sgRNA) are not capped or polyadenylated. We have determined that PMV uses a cap‐independent mechanism of translation. A 116‐nucleotide translational enhancer (TE) region on the 3′‐untranslated region of both the gRNA and sgRNA has been identified. The TE is required for efficient translation of viral proteins in vitro. For mutants with a compromised TE, addition of cap analog, or transposition of the cis‐active TE to another location, both restored translational competence of the 5′‐proximal sgRNA genes in vitro.
Ubiquinone (coenzyme Q10) binding sites: Low dielectric constant of the gate prevents the escape of the semiquinone
Authors: Shinkarev V.P.
Published: April 2006

The photosynthetic reaction center (RC) from purple bacteria is frequently used as a model for the interaction of ubiquinones (coenzyme Q) with membrane proteins. Single‐turnover flash activation of RC leads to formation of the semiquinone (SQ) of the secondary acceptor quinone after odd flashes and quinol after even flashes. The ubiquinol escapes the binding site in ⩽1 ms, while the SQ does not leave the binding site for at least 5 min. Observed difference between these times suggests a large energetic barrier for the SQ. However, high apparent dielectric constant in the vicinity of the quinone ring (⩾25) results in a relatively small electrostatic energy of SQ stabilization. To resolve this apparent contradiction I suggest that a significant part of the kinetic stabilization of the SQ is achieved by the special topology of the binding site in which quinone can exit the binding site only by moving its headgroup toward the center of the membrane. The large energetic penalty of transferring the charged headgroup to the membrane dielectric can explain the observed kinetic stability of the SQ.
Mouse model of human infertility: Transient and local inhibition of endometrial STAT‐3 activation results in implantation failure
Authors: Nakamura Hitomi , Kimura Tadashi , Koyama Shinsuke , Ogita Kazuhide , Tsutsui Tateki , Shimoya Koichiro , Taniguchi Takeshi , Koyama Masayasu , Kaneda Yasufumi , Murata Yuji
Published: April 2006

Embryo implantation involves a series of biochemical reactions and its failure is an important therapeutic target of infertility treatment. We established an infertile mouse model using transient and local suppression of signal transducer and activator of transcription‐3 (STAT‐3) activity by STAT‐3 decoy transfer into the uterine cavity during implantation, resulting in <30% implantation. This infertility is caused by suppression of decidualization, which is indispensable for implantation, and independent of progesterone. These conditions may mimic clinically unexplained infertility. Our results suggest that STAT‐3 could be a useful target for diagnosis and therapy of human implantation failure.
Neural mechanisms mediating responses to abutting gratings: Luminance edgesvs.illusory contours
Authors: SONG YUNING , BAKER CURTIS L.
Published: April 2006

The discontinuities of phase-shifted abutting line gratings give rise to perception of an “illusory contour” (IC) along the line terminations. Neuronal responses to such ICs have been interpreted as evidence for a specialized visual mechanism, since such responses cannot be predicted from conventional linear receptive fields. However, when the spatial scale of the component gratings (carriers) is large compared to the neuron's luminance passband, these IC responses might be evoked simply by the luminance edges at the line terminations. Thus by presenting abutting gratings at a series of carrier spatial scales to cat A18 neurons, we were able to distinguish genuine nonlinear responses from those due to luminance edges. Around half of the neurons (both simple and complex types) showed a bimodal response pattern to abutting gratings: one peak at a low carrier spatial frequency range that overlapped with the luminance passband, and a second distinct peak at much higher frequencies beyond the neuron's grating resolution. For those bimodally responding neurons, the low-frequency responses were sensitive to carrier phase, but the high-frequency responses were phase-invariant. Thus the responses at low carrier spatial frequencies could be understoodviaa linear model, while the higher frequency responses represented genuine nonlinear IC processing. IC responsive neurons also demonstrated somewhat lower spatial preference to the periodic contours (envelopes) compared to gratings, but the optimal orientation and motion direction for both were quite similar. The nonlinear responses to ICs could be explained by the same energy mechanism underlying responses to second-order stimuli such as contrast-modulated gratings. Similar neuronal preferences for ICs and for gratings may contribute to the form-cue invariant perception of moving contours.
MODERNITY AGAINST MODERNITY: WANG HUI'S CRITICAL HISTORY OF CHINESE THOUGHT
Authors: MURTHY VIREN
Published: April 2006

In the last fifteen years or so, Chinese intellectuals have been heatedly debating the complex relationships between China's prospects, China's past, and the modern predicament. In this context Wang Hui has emerged as one of China's most challenging and controversial intellectuals. His work is controversial. At a time when intellectuals take modernization as a goal, Wang has consistently voiced reservations. Readers find his works challenging because, instead of criticizing modernity or capitalism from simple moral tenets, Wang has always sought to redefine the terms of the debate through detailed and sensitive historical analysis. Hence amidst his busy life as editor, professor, and polemicist, Wang has devoted more than ten years to writing his magisterial four volume book The Rise of Modern Chinese Thought (Zhongguo sixiang de xingqi), in which he fundamentally rethinks the relationship between modernity and Chinese thought. However, Wang's book is not just an immense contribution to historical and historiographical scholarship; his work is a self-consciously political intervention. Specifically, he highlights the role of intellectual history as critique and attempts to recover repressed elements of the past in order to question the structures that govern the present. In the last line of the conclusion to his book he writes, “the history that modernity loftily and even proudly rejects contains the inspiration and possibilities for overcoming its crisis.” Taking China as his focus, Wang attempts to write this history.
Tryptophan-Niacin Metabolism in Rat with Puromycin Aminonucleoside-Induced Nephrosis
Authors: Egashira Yukari , Nagaki Shin , Sanada Hiroo
Published: April 2006

We investigated the change of tryptophan-niacin metabolism in rats with puromycin aminonucleoside PAN-induced nephrosis, the mechanisms responsible for their change of urinary excretion of nicotinamide and its metabolites, and the role of the kidney in tryptophan-niacin conversion. PAN-treated rats were intraperitoneally injected once with a 1.0% (w/v) solution of PAN at a dose of 100 mg/kg body weight. The collection of 24-hour urine was conducted 8 days after PAN injection. Daily urinary excretion of nicotinamide and its metabolites, liver and blood NAD, and key enzyme activities of tryptophan-niacin metabolism were determined. In PAN-treated rats, the sum of urinary excretion of nicotinamide and its metabolites was significantly lower compared with controls. The kidneyα-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) activity in the PAN-treated group was significantly decreased by 50%, compared with the control group. Although kidney ACMSD activity was reduced, the conversion of tryptophan to niacin tended to be lower in the PAN-treated rats. A decrease in urinary excretion of niacin and the conversion of tryptophan to niacin in nephrotic rats may contribute to a low level of blood tryptophan. The role of kidney ACMSD activity may be minimal concerning tryptophan-niacin conversion under this experimental condition.
Cloning of the Bovine β-Carotene-15,15’-Oxygenase and Expression in Gonadal Tissues
Authors: Morales Adriana , Rosas Antonio , González Adriana , Antaramian Anaid , Varela-Echavarría Alfredo , Shimada Armando , Mora Ofelia
Published: April 2006

β-carotene-15,15’-oxygenase (βCO), found mainly in intestinal mucosa and liver, is the enzyme responsible for cleaving β-carotene into retinal, which can be used or stored at these sites or carried by the bloodstream to different target cells within the body. We isolated the cDNA for bovine βCO and demonstrated its expression in gonadal tissues. A cDNA of 2130 base pairs (bp) was obtained by reverse transcriptase-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE), using degenerate oligonucleotides; the deduced protein shared an identity of 75% with its homologues from other mammalian species. In order to evaluate the expression of this enzyme, we performed RT-PCR and in situ hybridizations in the ovary and testis of bovines. RT-PCR showed the expression of βCO in testis, ovary, and cultured granulosa cells. In situ hybridization of complete ovary and testis revealed expression in granulosa cells and the corpus luteum in the ovary and in germinal and interstitial cells in the testis. These results suggest that beta-carotene could act as a local source of retinoids, which have been shown to be important during proliferation, differentiation, and maturation of both female and male germinal cells.
Melt inclusion record of the conditions of ascent, degassing, and extrusion of volatile‐rich alkali basalt during the powerful 2002 flank eruption of Mount Etna (Italy)
Authors: Spilliaert N. , Allard P. , Métrich N. , Sobolev A. V.
Published: April 2006

Two unusual, highly explosive flank eruptions succeeded on Mount Etna in July August 2001 and in October 2002 to January 2003, raising the possibility of changing magmatic conditions. Here we decipher the origin and mechanisms of the second eruption from the composition and volatile (H2O, CO2, S, Cl) content of olivine‐hosted melt inclusions in explosive products from its south flank vents. Our results demonstrate that powerful lava fountains and ash columns at the eruption onset were sustained by closed system ascent of a batch of primitive, volatile‐rich (≥4 wt %) basaltic magma that rose from ≥10 km depth below sea level (bsl) and suddenly extruded through 2001 fractures maintained opened by eastward flank spreading. This magma, the most primitive for 240 years, probably represents the alkali‐rich parental end‐member responsible for Etna lavas' evolution since the early 1970s. Few of it was directly extruded at the eruption onset, but its input likely pressurized the shallow plumbing system several weeks before the eruption. This latter was subsequently fed by the extrusion and degassing of larger amounts of the same, but slightly more evolved, magma that were ponding at 6–4 km bsl, in agreement with seismic data and with the lack of preeruptive SO2 accumulation above the initial depth of sulphur exsolution (∼3 km bsl). We find that while ponding, this magma was flushed and dehydrated by a CO2‐rich gas phase of deeper derivation, a process that may commonly affect the plumbing system of Etna and other alkali basaltic volcanoes.
Equation of state and structural properties of the Weeks-Chandler-Andersen fluid
Authors: Heyes David M. , Okumura Hisashi
Published: April 2006

Molecular dynamics simulations have been carried out for the equation of state and percolation properties of the Weeks-Chandler-Andersen (WCA) system in its fluid phase as functions of density and temperature. The compressibility factor Z collapses well for the various isotherms, using an effective particle diameter for the WCA particle which is (in the usual WCA reduced units) σe=21∕6∕(1+T)1∕6, where T is the temperature. A corresponding “effective” packing fraction is ζe=πσe3N∕6V, for N particles in volume V, which therefore scales out the effects of temperature. Using ζe the simulation derived Z can be fitted to a simple analytic form which is similar to the Carnahan-Starling hard sphere equation of state and which is valid at all temperatures and densities where the WCA fluid is thermodynamically stable. The data, however, are not scalable onto the hard sphere equation of state for the complete packing fraction range. We explored the continuum percolation behavior of the WCA fluids. The percolation distance σp for the various states collapses well onto a single curve when plotted as σp∕σe against ζe. The ratio σp∕σe exhibits a monotonic decrease with increasing ζe between the percolation line for permeable spheres and the glass transition limit, where σp∕σe≃1. The percolation packing fraction was calculated as a function of effective packing fraction and fitted to an empirical expression. The local coordination number at the percolation threshold showed a transition between the soft core and hard core limits from ca. 2:74 to 1:5, as previously demonstrated in the literature for true hard spheres. A number of simple analytic expressions that represent quite well the percolation characteristics of the WCA system are proposed.
An internal antisense RNA regulates expression of the photosynthesis gene
isiA
Authors: Dühring Ulf , Axmann Ilka M. , Hess Wolfgang R. , Wilde Annegret
Published: April 2006

Small regulatory noncoding RNAs exist in both eukaryotic and prokaryotic organisms. Most of these RNA transcripts are trans-encoded RNAs with short and only partial antisense complementarity to their target RNAs, which regulate gene expression by modifying mRNA stability and translation. In contrast, reports on the function of cis-encoded, perfectly complementary antisense RNAs in eubacteria are rare. Cyanobacteria respond to iron deficiency by expressing IsiA (iron stress-induced protein A), which forms a giant ring structure around photosystem I. Here, we show that this process is controlled by IsrR (iron stress-repressed RNA), a cis-encoded antisense RNA transcribed from the
isiA
noncoding strand. Artificial overexpression of IsrR under iron stress causes a strongly diminished number of IsiA–photosystem I supercomplexes, whereas IsrR depletion results in premature expression of IsiA. The coupled degradation of IsrR/
isiA
mRNA duplexes appears to be a reversible switch that can respond to environmental changes. IsrR is the only RNA known so far to regulate a photosynthesis component.
Ghrelin and cholecystokinin in term and preterm human breast milk
Authors: Kierson Jennifer A. , Dimatteo Darlise M. , Locke Robert G. , MacKley Amy B. , Spear Michael L.
Published: April 2006

Aim: To determine whether ghrelin and cholecystokinin (CCK) are present in significant quantities in term and preterm human breast milk, and to identify their source. Methods: Samples were collected from 10 mothers who delivered term infants and 10 mothers who delivered preterm infants. Estimated fat content was measured. Ghrelin and CCK levels were measured in whole and skim breast milk samples using radioimmunoassays (RIA). Reverse transcriptase‐polymerase chain reaction (RT‐PCR) was performed using RNA from human mammary epithelial cells (hMECs) and mammary gland with primers specific to ghrelin. Results: The median ghrelin level in whole breast milk was 2125 pg/ml, which is significantly higher than normal plasma levels. There was a direct correlation between whole milk ghrelin levels and estimated milk fat content (r=0.84, p<0.001). Both the mammary gland and hMECs produced ghrelin. While CCK was detected in some samples, levels were insignificant. Infant gestational age, birthweight, maternal age, and maternal pre‐pregnancy body mass index did not significantly affect the results.

Conclusion: Ghrelin, but not CCK, is present in breast milk. Since the mammary gland produces ghrelin message, and ghrelin levels in breast milk are higher than those found in plasma, we conclude that ghrelin is produced and secreted by the breast.
Ancient DNA forces reconsideration of evolutionary history of Mediterranean pygmy elephantids
Authors: Poulakakis Nikos , Parmakelis Aris , Lymberakis Petros , Mylonas Moysis , Zouros Eleftherios , Reese David S , Glaberman Scott , Caccone Adalgisa
Published: April 2006

During the Pleistocene pygmy elephantids, some only a quarter of their ancestors' size, were present on Mediterranean islands until about 10 000 years ago (y.a.). Using a new methodology for ancient DNA (aDNA) studies, the whole genomic multiple displacement amplification method, we were able to retrieve cytochromeb(cytb) DNA fragments from 4200 to 800 000 y.a. specimens from island and mainland samples, including pygmy and normal-sized forms. The short DNA sequence (43 bp) retrieved from the 800 000 y.a. sample is one of the oldest DNA fragment ever retrieved. Duplication of the experiments in two laboratories, the occurrence of three diagnostic sites and the results of the phylogenetic analyses strongly support its authenticity. Our results challenge the prevailing view that pygmy elephantids of the eastern Mediterranean originated exclusively fromElephas, suggesting independent histories of dwarfism and the presence of both pygmy mammoths and elephant-like taxa on these islands. Based on our molecular data, the origin of the Tilos and Cyprus elephantids from a lineage within the genusElephasis confirmed, while the DNA sequence from the Cretan sample falls clearly within the mammoth clade. Thus, the nameMammuthus creticusrather thanElephas creticus, seems to be justified for this form. Our findings also suggest a need to re-evaluate the evolutionary history of the Sicilian/Maltese species, traditionally included in the genusElephas.
Adaptive genetic complementarity in mate choice coexists with selection for elaborate sexual traits
Authors: Oh Kevin P , Badyaev Alexander V
Published: April 2006

Choice of genetically unrelated mates is widely documented, yet it is not known how self-referential mate choice can co-occur with commonly observed directional selection on sexual displays. Across 10 breeding seasons in a wild bird population, we found strong fitness benefits of matings between genetically unrelated partners and show that self-referential choice of genetically unrelated mates alternates with sexual selection on elaborate plumage. Seasonal cycles of diminishing variation in ornamentation, caused by early pairing of the most elaborated males, and influx of increasingly genetically unrelated available mates caused by female-biased dispersal, lead to temporal fluctuations in the target of mate choice and enabled coexistence of directional selection for ornament elaboration with adaptive pairing of genetically unrelated partners.
Heterogeneous three-dimensional anatomical and electrophysiological model of human atria
Authors: Seemann Gunnar , Höper Christine , Sachse Frank B , Dössel Olaf , Holden Arun V , Zhang Henggui
Published: April 2006

Investigating the mechanisms underlying the genesis and conduction of electrical excitation in the atria at physiological and pathological states is of great importance. To provide knowledge concerning the mechanisms of excitation, we constructed a biophysical detailed and anatomically accurate computer model of human atria that incorporates both structural and electrophysiological heterogeneities.

The three-dimensional geometry was extracted from the visible female dataset. The sinoatrial node (SAN) and atrium, including crista terminalis (CT), pectinate muscles (PM), appendages (APG) and Bachmann's bundle (BB) were segmented in this work. Fibre orientation in CT, PM and BB was set to local longitudinal direction.

Descriptions for all used cell types were based on modifications of the Courtemanche
et al
. model of a human atrial cell. Maximum conductances of

,

and

were modified for PM, CT, APG and atrioventricular ring to reproduce measured action potentials (AP). Pacemaker activity in the human SAN was reproduced by removing

, but including

,

, and gradients of channel conductances as described in previous studies for heterogeneous rabbit SAN.

Anisotropic conduction was computed with a monodomain model using the finite element method. The transversal to longitudinal ratio of conductivity for PM, CT and BB was 1 : 9. Atrial working myocardium (AWM) was set to be isotropic.

Simulation of atrial electrophysiology showed initiation of APs in the SAN centre. The excitation spread afterwards to the periphery near to the region of the CT and preferentially towards the atrioventricular region. The excitation extends over the right atrium along PM. Both CT and PM activated the right AWM. Earliest activation of the left atrium was through BB and excitation spread over to the APG. The conduction velocities were 0.6 m s
−1
for AWM, 1.2 m s
−1
for CT, 1.6 m s
−1
for PM and 1.1 m s
−1
for BB at a rate of 63 bpm.

The simulations revealed that bundles form dominant pathways for atrial conduction. The preferential conduction towards CT and along PM is comparable with clinical mapping. Repolarization is more homogeneous than excitation due to the heterogeneous distribution of electrophysiological properties and hence the action potential duration.
Theoretical models of adaptive energy management in small wintering birds
Authors: Brodin Anders
Published: April 2006

Many small passerines are resident in forests with very cold winters. Considering their size and the adverse conditions, this is a remarkable feat that requires optimal energy management in several respects, for example regulation of body fat reserves, food hoarding and night-time hypothermia. Besides their beneficial effect on survival, these behaviours also entail various costs. The scenario is complex with many potentially important factors, and this has made ‘the little bird in winter’ a popular topic for theoretic modellers. Many predictions could have been made intuitively, but models have been especially important when many factors interact. Predictions that hardly could have been made without models include: (i) the minimum mortality occurs at the fat level where the marginal values of starvation risk and predation risk are equal; (ii) starvation risk may also decrease when food requirement increases; (iii) mortality from starvation may correlate positively with fat reserves; (iv) the existence of food stores can increase fitness substantially even if the food is not eaten; (v) environmental changes may induce increases or decreases in the level of reserves depending on whether changes are temporary or permanent; and (vi) hoarding can also evolve under seemingly group-selectionistic conditions.
Expression of CD163 in dermatofibroma, cellular fibrous histiocytoma, and dermatofibrosarcoma protuberans: comparison with CD68, CD34, and Factor XIIIa
Authors: Sachdev Reena , Sundram Uma
Published: April 2006

Background:  Distinction between cellular fibrous histiocytomas (FHs) with a deep component and dermatofibrosarcoma protuberans (DFSPs) can pose diagnostic problems. While CD68, CD34, and Factor XIIIa are helpful in distinguishing between these entities, none are diagnostically absolute. Recent work with CD163, a hemoglobin scavenger receptor, has demonstrated that this marker has high specificity for monocytes, macrophages, and histiocytes. Our goal is to evaluate the utility of CD163 in the diagnosis of dermatofibromas (DFs), cellular FHs, and DFSPs.

Methods:  Sixty cases including 19 DFs, 23 cellular FHs with a deep component, and 18 DFSPs were tested with antibodies against CD163, CD68, CD34, and Factor XIIIa.

Results:  CD163 was expressed in 17/19 (89%) DFs, 23/23 (100%) cellular FHs, and 3/18 (17%) DFSPs. CD68 was positive in 8/19 (42%) DFs, 19/23 (83%) cellular FHs, and 1/16 (6%) DFSPs. CD34 was expressed in 1/19 (5%) DFs, 5/23 (22%) cellular FHs, and 100% of DFSPs. Factor XIIIa labeled 4/19 (21%) DFs, 11/23 (48%) cellular FHs, and 0/17 cases of DFSPs.

Conclusions:  CD163 expression is helpful in distinguishing between cellular FHs and DFSPs and will be useful in a panel of antibodies when these entities are in the differential diagnosis.
Small‐scale fluid motion mediates growth and nutrient uptake of Selenastrum capricornutum
Authors: WARNAARS T. A. , HONDZO M.
Published: April 2006

1. A fluid‐flow reactor using submersible speakers was constructed to generate small‐scale fluid motion similar to conditions measured in open water environments; flow was quantified by particle image velocimetry. Additionally a Couette‐type rotating cylinder was used to generate shear flows; flow was quantified using an optical hotwire probe and torque measurements. Growth rates of the green alga Selenastrum capricornutum were determined from changes in cell counts and viability was tested using the fluorogenic probe fluoresceine diacetate.

2. Evidence that fluid motion directly affects growth rates was obtained as a significant difference between growth in a moving versus non‐moving fluid. A near 2‐fold increase in growth rate was achieved for an energy dissipation rate of ɛ = 10−7 m2 s−3; a rate common in lakes and oceans. The onset of the viability equilibrium, identified as the day of the test period when the number of active cells equalled non‐active cells, was delayed by 2 days for moving fluid conditions as compared with a non‐moving fluid.

3. Nutrient uptake was determined by a decrease in the bulk fluid concentration and cellular phosphorus concentration was also estimated. The thickness of the diffusive sublayer surrounding a cell, a zone dominated by molecular diffusion, was estimated. Increasing fluid motion was found to decrease the thickness of this layer. The Sherwood number (ratio of total mass flux to molecular mass flux) showed that advective flux surrounding cells dominated molecular diffusion flux with regard to Péclet numbers (ratio of advective transport to molecular diffusion transport). Fluid motion facilitated uptake rates and resulted in increased growth rates, compared with no‐flow conditions. The rate‐of‐rotation and the rate‐of‐strain in a moving fluid equally mediated the diffusive sublayer thickness surrounding the cells. Our study demonstrates that small‐scale fluid motion mediates algal growth kinetics and therefore should be included in predictive models for algal blooms.
Role of TNF‐αin muscularis inflammation and motility disorder in a TNBS‐induced colitis model: clues from TNF‐α‐deficient mice
Authors: Kinoshita K. , Hori M. , Fujisawa M. , Sato K. , Ohama T. , Momotani E. , Ozaki H.
Published: April 2006

Abstract Macroscopic and histological analysis revealed that the colonic inflammation induced by 2,4,6‐trinitrobenzenesulphonic acid (TNBS) was of lower grade in tumour necrosis factor‐α(TNF‐α)−/−mice than in wild‐type mice. Myeloperoxidase activity, an indicator of neutrophilic infiltration, was also low in both the mucosal and smooth muscle layer of the TNF‐α−/−mouse colon. After the induction of inflammation with TNBS, the levels of proinflammatory cytokines, such as TNF‐α, interleukin‐1βand interleukin‐6, were elevated both in the inflamed mucosa and muscle layers in the wild‐type mice; however, the productions of these cytokines were greatly reduced in the TNF‐α−/−mouse colon. The contractions of isolated colonic smooth muscle strips induced by several stimulatory agents were significantly decreased after treatment with TNBS in wild‐type mice; however, these contractions were scarcely affected in TNF‐α−/−mice. Finally, using the organ culture method, we found that TNF‐αdirectly (independent of mucosal inflammation) disturbs the smooth muscle function. These results suggest that TNF‐αplays an essential role not only in mucosal inflammation but also in muscularis inflammation in the colon of mice with TNBS‐induced colitis, and that TNF‐αdirectly induces motor dysfunctions by acting on the smooth muscle.
Immunology of canine leishmaniasis
Authors: BARBIÉRI C. L.
Published: April 2006

The role of dogs as the main reservoir of visceral leishmaniasis has led to an increased interest in the immune responses and in Leishmania antigens implicated in protective cellular immunity in canine visceral leishmaniasis. The primary goal is to control the prevalence of human disease. Immune responses in canine visceral leishmaniasis are reviewed. Cellular immune responses toward a Th1 subset mediated by IFN‐γ and TNF‐α predominate in asymptomatic dogs exhibiting apparent resistance to visceral leishmaniasis. On the other hand, while the role of Th2 cytokines, such as IL‐4 and IL‐10, in symptomatic animals is still controversial, there is increasing evidence for a correlation of these cytokines with progressive disease. CD8+ cytotoxic T cells seem also likely to be involved in resistance to visceral leishmaniasis. Several Leishmania antigens implicated in protective immune responses are described and some pivotal points for development of an effective vaccine against canine visceral leishmaniasis are discussed.
Laser vs. settling velocity differences in silt grainsize measurements: estimation of palaeocurrent vigour
Authors: MCCAVE I. N. , HALL I. R. , BIANCHI G. G.
Published: April 2006

The use of grain‐size distribution of muds for the reconstruction of past deep ocean currents is becoming established and applied in the palaeoceanographic community. The methods are also applicable to shallow marine and tidal flat muds with similar inferences concerning the energy of wave and current sorting being drawn. Fine sediment grain‐size distributions can be obtained using a variety of instruments based on fundamentally different theoretical principles. These machines may give varying, sometimes misleading, results giving divergent interpretations of flow speed history. The new evidence presented here, combined with earlier work, suggests that of the three most commonly used analytical methods for fine silts with clays, settling velocity (Sedigraph) should be the method and instrument of choice, with electrical resistance pulse counters (e.g. Coulter Counter) as a suitable alternative. The data also show that laser particle sizers should be avoided for palaeocurrent reconstructions because the measured size of platey minerals can be dominated by their large projected area. This causes them to be recorded as the same size as larger equant grains although they have much smaller settling velocity and were deposited in aggregates. This produces results with a weaker relationship to the dynamics of deposition. The central problem is thus that some coarse clay/fine silt is recorded as medium to coarse silt, the key size in the ‘sortable silt’ mean size method of inferring changes in flow speed. For coarse silts (e.g. loess) the laser gives more satisfactory results.
Management of mutual health organizations in Ghana
Authors: Baltussen R. , Bruce E. , Rhodes G. , Narh‐Bana S. A. , Agyepong I.
Published: April 2006

Objective  Mutual Health Organizations (MHO) emerged in Ghana in the mid‐1990s. The organizational structure and financial management of private and public MHO hold important lessons for the development of national health insurance in Ghana, but there is little evidence to date on their features. This paper aims at filling this data gap, and at making recommendations to Ghanaian authorities on how to stimulate the success of MHO.

Methods  Survey among 45 private and public MHO in Ghana in 2004–2005, asking questions on their structure, financial management and financial position.

Results  Private MHO had more autonomy in setting premiums and benefit packages, and had higher community participation in meetings than public MHO. MHO in general had few measures in place to control moral hazard and reduce adverse selection, but more measures to control fraud and prevent cost escalation. The vast majority of schemes were managed by formally trained and paid staff. The financial results varied considerably.

Conclusions  Ghanaian authorities regulate the newly established public MHO, but may do good by leaving them a certain level of autonomy in decision‐making and secure community participation. The financial management of MHO is suboptimal, which indicates the need for technical assistance.
Evaluation of antifungals in the surgical intensive care unit: a multi‐institutional study
Authors: Garey Kevin W. , Neuhauser Melinda M. , Bearden David T. , Cannon Joan P. , Lewis Russell E. , Gentry Layne O. , Kontoyiannis Dimitrios P.
Published: April 2006

In the USA, >50% of candidemia episodes occur in medical or surgical intensive care units (SICU). However, studies focused on patterns and rationale for antifungal use are lacking. The objective of this study was to evaluate systemic antifungal usage in SICU patients. Retrospective audit of SICU patients receiving antifungal therapy from four American hospitals. Medical records were reviewed for demographics, hospital variables, microbiology results, antifungal regimens and indications for therapy. A total of 2411 patient‐days of antifungal use were evaluated in 225 patients. Fluconazole was the most frequently prescribed antifungal (1846 patient‐days) followed by amphotericin B deoxycholate (251 patient‐days), lipid formulations of amphotericin B (201 patient‐days), itraconazole (71 patient‐days), and caspofungin (42 patient‐days). Antifungals were prescribed empirically (44%), for preemptive therapy in critically ill patients colonised with Candida (43%), or for candidiasis (12%). Candida species were recovered from 98% of patients with positive fungal cultures most commonly from pulmonary (53%) or urinary sources (17%). Fluconazole is the most frequently prescribed antifungal agent in SICUs and is most often prescribed for empiric or preemptive indications. Research efforts to identify patients who warrant preemptive antifungal therapy for invasive candidiasis could dramatically change antifungal prescribing patterns in the SICU.
In vitro activities of new and conventional antimycotics against fluconazole‐susceptible and non‐susceptible Brazilian Candida spp. isolates
Authors: Alves S. H. , Da Matta D. A. , Azevedo A. C. , Loreto E. S. , Boff E. , Santurio J. M. , Guarro J.
Published: April 2006

The substantial increase in the rate of azole resistant Candida spp. yeast infections has become a serious treatment problem requiring new and more active antifungal agents. In this study, the in vitro activities of ravuconazole and albaconazole were compared with those of amphotericin B, flucytosine, itraconazole and fluconazole against 162 Brazilian isolates of Candida spp. from which 48 isolates had previously shown lower susceptibility or resistance to fluconazole. Ravuconazole susceptibility ranged from 84.6% (Candida albicans) to 100% for other species and albaconazole MIC90 was ≤1.0 μg ml−1 for all the species emphasising the potent activity of these triazoles. To our knowledge this is the first study evaluating the susceptibility of C. dubliniensis to albaconazole.
Evaluation of platelet kinetics in patients with liver cirrhosis: Similarity to idiopathic thrombocytopenic purpura
Authors: Kajihara Mikio , Okazaki Yuka , Kato Shinzo , Ishii Hiromasa , Kawakami Yutaka , Ikeda Yasuo , Kuwana Masataka
Published: April 2006

Background:  Thrombocytopenia is a common manifestation of liver cirrhosis (LC), but its underlying mechanism is not fully understood. The purpose of the present paper was to evaluate the platelet kinetics in LC patients by examining several non‐invasive convenient markers.

Methods:  Fifty‐seven LC patients, 32 patients with idiopathic thrombocytopenic purpura (ITP), 12 with aplastic anemia (AA), and 29 healthy individuals were studied. Plasma thrombopoietin was measured by enzyme‐linked immunosorbent assay. Absolute reticulated platelet (RP) count and plasma glycocalicin were used as indices for thrombopoiesis, and the indices for platelet turnover were the RP proportion and the plasma glycocalicin normalized to the individual platelet count (GCI).

Results:  There was no difference in thrombopoietin levels between LC patients and healthy controls. The RP proportion and GCI were significantly higher and the absolute RP count and glycocalicin significantly lower in LC patients than in healthy controls. These markers in ITP and LC patients were comparable, but significantly different from those in AA patients. The bone marrow megakaryocyte density in LC and ITP patients was similar, and significantly higher than in AA patients.

Conclusions:  Cirrhotic thrombocytopenia is a multifactorial condition involving accelerated platelet turnover and moderately impaired thrombopoiesis. Thrombopoietin deficiency is unlikely to be the primary contributor to cirrhotic thrombocytopenia.
Optimal eradication: when to stop looking for an invasive plant
Authors: Regan Tracey J. , McCarthy Michael A. , Baxter Peter W. J. , Dane Panetta F. , Possingham Hugh P.
Published: April 2006

The notion of being sure that you have completely eradicated an invasive species is fanciful because of imperfect detection and persistent seed banks. Eradication is commonly declared either on an ad hoc basis, on notions of seed bank longevity, or on setting arbitrary thresholds of 1% or 5% confidence that the species is not present. Rather than declaring eradication at some arbitrary level of confidence, we take an economic approach in which we stop looking when the expected costs outweigh the expected benefits. We develop theory that determines the number of years of absent surveys required to minimize the net expected cost. Given detection of a species is imperfect, the optimal stopping time is a trade‐off between the cost of continued surveying and the cost of escape and damage if eradication is declared too soon. A simple rule of thumb compares well to the exact optimal solution using stochastic dynamic programming. Application of the approach to the eradication programme of Helenium amarum reveals that the actual stopping time was a precautionary one given the ranges for each parameter.
Obesity risk associated with the K121Q polymorphism of the glycoprotein PC‐1 gene
Authors: Wan C. , Zhang T. , Wang B. , Han Y. , Zhang C. , Zhang Y. , Gong H. , Jin F. , Wang L.
Published: April 2006

Background:  Obesity is considered to be a multifactorial trait resulting from the combined influence of genetic and environmental determinants. Insulin resistance plays an important role in the development of obesity. Plasma‐cell membrane differentiation antigene‐1 (PC‐1) inhibits insulin receptor signalling when overexpressed and thus causes insulin resistance. PC‐1 gene polymorphism might be associated with adipocyte metabolism disturbance and energy imbalance. The purpose of this study was to determine whether K121Q polymorphism in PC‐1 gene is involved in obesity susceptibility in Chinese Han population.

Methods:  The genotype of the polymorphism was determined using polymerase chain reaction‐restriction fragment length polymorphism analysis for 338 unrelated subjects of Beijing, China. Their Body mass index (BMI), plasma glucose, total cholesterol, triglyceride, high‐density lipoprotein cholesterol (HDL), free fatty acid (FFA) and insulin level were measured. Chi‐square analyses were applied to test the significance differences in genotypic and allelic frequencies. Association studies were undertaken using the t‐test and logistic regression analyses.

Results:  The obese had significantly higher frequency of KQ/QQ genotype or Q allele than non‐obese in females (26.7% vs. 10.9%, p = 0.014 and 13.3% vs. 5.5%, p = 0.021). Significant elevation of insulin amongst the Q121 carrier women in obesity individuals and higher FFA level of Q121 carrier men in non‐obese controls (BMI ≤ 23 kg/m2) were observed. Binary logistic regression analysis revealed that PC‐1 genotype together with higher glucose, total cholesterol, triglyceride and serum HDL were independently associated with the presence of obesity.

Conclusions:  The observed genotype distributions revealed a significant association of PC‐1 K121Q with obesity. PC‐1 Q121 carriers are more likely to be insulin‐resistant or get fatter in respect to KK subjects and carriers of the Q allele are at higher risk for the development of obesity in female.
Ethische Konflikte im Gesundheitswesen
Authors: Kliemt Hartmut
Published: April 2006

The public good provided by public health care is not the maintenance of citizens’ health but rather the maintenance of the legal order and the citizens’ support for it. Several policy proposals for achieving the aim of supporting the rule of law by minimal means of public health care provision are explored. A system of assigning limited amounts of guaranteed health care that are provided in competitive processes below market clearing prices is suggested. We are seeking for minimum public health care under the constraint of maintaining the legal order rather than solving a maximization problem.
Tomato is a highly effective vehicle for expression and oral immunization with Norwalk virus capsid protein
Authors: Zhang Xiuren , Buehner Norene A. , Hutson Anne M. , Estes Mary K. , Mason Hugh S.
Published: April 2006

Norwalk virus (NV) is an important agent of epidemic gastroenteritis, and an oral subunit vaccine shows potential for protection. Recombinant Norwalk virus (rNV) capsid protein expressed in plants assembles virus‐like particles (VLPs) that are orally immunogenic in mice and humans. In this article we examine rNV expression in tomato and potato using a plant‐optimized gene, and test the immunogenicity of dried tomato fruit and potato tuber fed to mice. The synthetic gene increased rNV expression fourfold in tomato and potato plants, which assembled VLP. Four doses of 0.4 g freeze‐dried tomato fruit containing 64 µg rNV (40 µg VLPs) induced NV‐specific serum IgG and mucosal IgA in ≥ 80% of mice, while doses of 0.8 g elicited systemic and mucosal antibody responses in all mice. Feedings of 1 g freeze‐dried potato tuber containing 120 µg rNV (90 µg VLPs) were required to produce 100% responsiveness. Oxidation of phenolic compounds upon rehydration of dried tuber caused significant VLP instability, thus decreasing immunogenicity. Air‐dried tomato fruit stimulated stronger immune responses than freeze‐dried fruit of the same mass, perhaps by limiting the destruction of plant cell matrix and membrane systems that occurs with freeze‐drying. Thus, rNV in dried transgenic tomato fruit was a more potent immunogen than that in dried potato tubers, based on the total VLPs ingested. These findings support the use of stabilized, dried tomato fruit for oral delivery of subunit vaccines.
Recommendations Implicit in Policy Defaults
Authors: McKenzie Craig R.M. , Liersch Michael J. , Finkelstein Stacey R.
Published: April 2006

Should people be considered organ donors after their death unless they request not to be, or should they not be considered donors unless they request to be? Because people tend to stay with the default in a variety of domains, policymakers' choice of default has large and often important effects. In the United States, where the organ-donation policy default is “not a donor,” about 5,000 people die every year because there are too few donors. Four experiments examined two domains—being an organ donor and saving for retirement—where default effects occur and have important implications. The results indicate that default effects occur in part because policymakers' attitudes can be revealed through their choice of default, and people perceive the default as indicating the recommended course of action. Policymakers need to be aware of the implicit messages conveyed by their choice of default.
Subcellular localization of epidermal growth factor receptor in human submandibular gland
Authors: Lantini M. S. , Cossu M. , Isola M. , Piras M. , Piludu M.
Published: April 2006

The subcellular distribution of the epidermal growth factor receptor (EGFr) was demonstrated in the normal human submandibular gland by means of immunogold cytochemistry. EGFr labelling appeared in both acinar and ductal cells, where strong immunoreactivity was associated with a tubulovesicular system near the basolateral surfaces. In addition, groups of reactive vesicles were highlighted among secretory granules of both serous and mucous cells and at the apex of ductal cells. Basolateral vesicles were interpreted as being a result of EGFr internalization after activation by an exogenous ligand, although the functional meaning of those located apically remains unclear.
Rho family GTPase inhibition reveals opposing effects of mitogen‐activated protein kinase kinase/extracellular signal‐regulated kinase and Janus kinase/signal transducer and activator of transcription signaling cascades on neuronal survival
Authors: Loucks F. Alexandra , Le Shoshona S. , Zimmermann Angela K. , Ryan Kristen R. , Barth Holger , Aktories Klaus , Linseman Daniel A.
Published: April 2006

Rho family GTPases promote the survival of certain neuronal populations. However, pro‐survival and pro‐death signaling pathways regulated downstream of Rho GTPases are largely unknown. Cerebellar granule neurons (CGNs) exposed to Clostridium difficile toxin B (ToxB), a monoglucosyltransferase that specifically inhibits Rho GTPases, die by a mitochondrial apoptotic cascade. Using a high‐throughput immunoblotting screen (BD Powerblot), we found that ToxB markedly reduced the expression of Rac1 and c‐Raf, upstream components of a Rac‐dependent mitogen‐activated protein (MAP) kinase pathway. Moreover, ToxB rapidly suppressed a p21‐activated kinase/MAP kinase kinase (MEK)/extracellular signal‐regulated kinase (ERK)1/2 signaling cascade that normally promotes degradation of the Bcl‐2 homology‐3 (BH3)‐only protein Bim, a key initiator of mitochondrial apoptosis. In contrast to c‐Raf down‐regulation, ToxB enhanced expression of the transcription factor, signal transducer and activator of transcription‐1 (STAT1). Both STAT1 up‐regulation and apoptosis induced by ToxB were prevented by a pan‐inhibitor of Janus kinases (JAKs), indicating that JAK/STAT signaling was pro‐apoptotic in CGNs. Most significantly, direct inhibition of MEK was sufficient to trigger JAK‐dependent STAT1 expression, suggesting that cross‐talk between MEK/ERK and JAK/STAT pathways plays a key role in regulating neuronal survival. Finally, ERK dephosphorylation and STAT1 up‐regulation induced by ToxB were mimicked by a dominant‐negative (N17) mutant of Rac1. These data suggest that the MEK/ERK cascade functions downstream of Rac GTPase to actively repress pro‐apoptotic JAK/STAT signaling in healthy CGNs.