bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphometric and taphonomic study of a ray-finned fish assemblage (Lepidotes buddhabutrensis, Semionotidae) from the Late Jurassic-earliest Cretaceous of NE Thailand
Authors: Deesri Uthumporn , Cavin Lionel , Claude Julien , Suteethorn Varavudh , Yuangdetkla Phisit
Published: May 2009

Most Mesozoic vertebrate species are represented by scarce and incomplete specimens, preventing statistical studies of morphometric features. Moreover, rich vertebrate assemblages are rarely excavated in conditions that allow taphonomical studies.Lepidotes buddhabutrensisis a common species found in the Late Jurassic–Early Cretaceous locality of Phu Nam Jun, Phu Kradung Formation, in NE Thailand. Individuals, collected during systematic excavation since 2002, show great variations in preservation states and body postures. In this paper we study the mode of variation of morphometric features of the fish population, the growth mode, and the relationship between morphology and size. We assess the range of variation in preservation and taphonomy, based on arbitrarily defined scales, to test if vertical variations occur in the sample of individuals within the site. We test possible favoured orientation of specimens within the assemblage. In contrast to preliminary field observations, statistical analyses show that all individuals belong to a single Gaussian population and that gross morphological shape variations are related only to size during fish growth.L. buddhabutrensisshows a positive allometric growth for the pectoral to dorsal, and pectoral to anal fin distances, and a negative allometric growth for the unpaired fins (dorsal and anal fins lengths). We detected no relationships between the vertical location of the fishes within the fossiliferous deposit and the body shape of the specimens, nor between the state of preservation and the taphonomy, but there are significant differences in the state of preservation according to the position of the fishes in the fossiliferous deposit. The occurrence of a single Gaussian population and the absence of morphological and preservational variations through the depositional column are evidence that the fish assemblage is probably the result of a single mass mortality event. The apparent diversity in morphology is probably due to variations in the mode of preservation. The fish appear to have been oriented by a current at the time of deposition at the top of the fossiliferous deposit only.
Elevated hydrostatic pressure activates sodium/hydrogen exchanger-1 in rat optic nerve head astrocytes
Authors: Mandal Amritlal , Shahidullah Mohammad , Delamere Nicholas A. , Terán Marcos A.
Published: May 2009

Optic nerve head astrocytes become abnormal in eyes that have elevated intraocular pressure, and cultured astrocytes display altered protein expression after being subjected for ≥1 days to elevated hydrostatic pressure. Here we show that 2-h elevated hydrostatic pressure (15 or 30 mmHg) causes phosphorylation of ERK1/2, ribosomal S6 protein kinase (p90RSK), and Na/H exchanger (NHE)1 in cultured rat optic nerve head astrocytes as judged by Western blot analysis. The MEK/ERK inhibitor U0126 abolished phosphorylation of NHE1 and p90RSK as well as ERK1/2. To examine NHE1 activity, cytoplasmic pH (pHi) was measured with BCECF and, in some experiments, cells were acidified by 5-min exposure to 20 mM ammonium chloride. Although baseline pHi was unaltered, the rate of pHi recovery from acidification was fourfold higher in pressure-treated astrocytes. In the presence of either U0126 or dimethylamiloride (DMA), an NHE inhibitor, hydrostatic pressure did not change the rate of pHi recovery. The findings are consistent with NHE1 activation due to phosphorylation of ERK1/2, p90RSK, and NHE1 that occurs in response to hydrostatic pressure. These responses may precede long-term changes of protein expression known to occur in pressure-stressed astrocytes.
Role of γ-glutamyl transpeptidase in redox regulation of K+ channel remodeling in postmyocardial infarction rat hearts
Authors: Zheng Ming-Qi , Tang Kang , Zimmerman Matthew C. , Liu Liping , Xie Bin , Rozanski George J.
Published: May 2009

γ-Glutamyl transpeptidase (γ-GT) is a key enzyme in GSH metabolism that regulates intracellular GSH levels in response to extracellular GSH (GSHo). The objective of this study was to identify the role of γ-GT in reversing pathogenic K+ channel remodeling in the diseased heart. Chronic ventricular dysfunction was induced in rats by myocardial infarction (MI), and studies were done after 6–8 wk. Biochemical assays of tissue extracts from post-MI hearts revealed significant increases in γ-GT activity in left ventricle (47%) and septum (28%) compared with sham hearts, which paralleled increases in protein abundance and mRNA. Voltage-clamp studies of isolated left ventricular myocytes from post-MI hearts showed that downregulation of transient outward K+ current ( Ito) was reversed after 4–5 h by 10 mmol/l GSHo or N-acetylcysteine (NACo), and that the effect of GSHo but not NACo was blocked by the γ-GT inhibitors, acivicin or S-hexyl-GSH. Inhibition of γ-glutamylcysteine synthetase by buthionine sulfoximine did not prevent upregulation of Ito by GSHo, suggesting that intracellular synthesis of GSH was not directly involved. However, pretreatment of post-MI myocytes with an SOD mimetic [manganese (III) tetrapyridylporphyrin] and catalase completely blocked recovery of Ito by GSHo. Confocal microscopy using the fluorogenic dye 2′,7′-dichlorodihydrofluorescein diacetate confirmed that GSHo increased reactive oxygen species (ROS) generation by post-MI myocytes and to a lesser extent in myocytes from sham hearts. Furthermore, GSHo-mediated upregulation of Ito was blocked by inhibitors of tyrosine kinase (genistein, lavendustin A, and AG1024) and thioredoxin reductase (auranofin and 13- cis-retinoic acid). These data suggest that GSHo elicits γ-GT- and ROS-dependent transactivation of tyrosine kinase signaling that upregulates K+ channel activity or expression via redox-mediated mechanisms. The signaling events stimulated by γ-GT catalysis of GSHo may be a therapeutic target to reverse pathogenic electrical remodeling of the failing heart.
Hypotension- and osmotically induced thirst in old Brown Norway rats
Authors: Thunhorst Robert L. , Beltz Terry G. , Johnson Alan Kim
Published: May 2009

Compared to young cohorts, old rats drink less water in response to several thirst-inducing stimuli. In these experiments, we characterized water drinking in response to hypotension and cellular dehydration in young (4 mo), middle-aged adult (12 mo) and old (29–30 mo) male Brown Norway rats. We injected the vasodilator, minoxidil as an intravenous bolus in a range of doses (0–20 mg/kg), so that drinking responses could be compared at equivalent reductions of arterial pressure. Old rats had greatly diminished reflex tachycardia and became significantly more hypotensive after minoxidil compared with young and middle-aged rats. When compared at equivalent reductions of arterial pressure, old rats drank one-third as much as middle-aged rats, and one-fifth as much as young rats. In addition, there were age-related deficits in drinking in response to a range of administered loads of sodium (0.15–2 M NaCl, 2 ml/100 g body wt). Urinary excretion of water and sodium in response to the loads was equivalent across ages. Both middle-aged and old rats were less able than young rats to repair their water deficits after sodium loading, attributable almost entirely to their reduced drinking responses compared with young rats. Lastly, age-related declines in drinking appeared to be more severe in response to hypotension than in response to cellular dehydration.
A Controlled Trial of Objective Measures of Sunscreen and Moisturizing Lotion
Authors: Elliott Tom , Nehl Eric J. , Glanz Karen
Published: May 2009

Taking an alcohol swab of a person's forearm and analyzing it using a spectrophotometer has been shown to be a reliable method for detecting the presence of sunscreen. The aims of this study were to determine if moisturizing lotions or other non-sunscreen products influence the absorbance readings from skin swabs in a controlled setting, and to establish the cutoff point in determining the presence or absence of sunscreen using a crystal cuvette instead of a plastic one. In a controlled trial of 30 volunteer office workers, absorbance readings from two popular brands of sunscreen with sun-protection factors (SPF) of 30 and 45 were compared with absorbance readings from two different moisturizing lotions, one with an SPF of 15 and another with no stated SPF. Moisturizers with SPF 15 tested positive for sunscreen, with absorbance readings (mean, 3.77; min, 3.30) comparable to sunblock with SPF 30 or 45 (mean, 3.51; min, 2.02). Moisturizers with no stated SPF factor tested negative for the presence of sunscreen, with extremely low absorbance readings (mean, 0.06; max, 0.19) similar to control readings. The skin swabbing technique remains a valid and useful method for detecting the presence of sunscreen and does not result in false positives when moisturizers with no stated SPF are present. Using a conservative cutoff point of 0.30 with a crystal cuvette reduces any chance of false-positive readings and remains robust when sunscreen of SPF 15 or higher is present. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1399–402)
Correlates of Carotid Plaque Presence and Composition as Measured by MRI
Authors: Wagenknecht Lynne , Wasserman Bruce , Chambless Lloyd , Coresh Josef , Folsom Aaron , Mosley Thomas , Ballantyne Christie , Sharrett Richey , Boerwinkle Eric
Published: May 2009

Background—

The composition of atherosclerotic plaque affects the likelihood of an atherothrombotic event, but prospective studies relating risk factors to carotid wall and plaque characteristics measured by MRI are lacking. We hypothesized that traditional risk factors are predictors of carotid wall and plaque characteristics measured 2 decades later.

Methods and Results—

A high-resolution contrast-enhanced MRI examination of the carotid artery was performed in 1769 participants. Measures of carotid wall volume and maximum thickness; lipid core presence, volume and maximum area; and fibrous cap thickness were performed centrally. The sample was, on average, 70 years of age, 57% female, 81% white, and 19% black. Greater age, total and low-density lipoprotein cholesterol, male sex, white race, diabetes, hypertension, and smoking as measured at baseline were all significant predictors of increased wall volume and maximum wall thickness 18 years later. An analysis of lipid core was restricted to the 1180 participants with maximum wall thickness ≥1.5 mm. Lipid core was observed in 569 individuals (weighted percentage, 42%). Baseline age and total and low-density lipoprotein cholesterol were predictors of presence of lipid core 18 years later; however, these relationships were attenuated after adjustment for wall thickness. Concurrently measured low-density lipoprotein cholesterol was associated with greater lipid core volume, independent of wall thickness. Concurrently measured glucose and body mass index were inversely associated fibrous cap thickness.

Conclusions—

Traditional atherosclerosis risk factors are related to increased wall volume and wall thickness 2 decades later, but they do not discriminate characteristics of plaque composition (core and cap) independent of wall size.
Cardiac Dysfunction Assessed by Echocardiographic Tissue Doppler Imaging Is an Independent Predictor of Mortality in the General Population
Authors: Mogelvang Rasmus , Sogaard Peter , Pedersen Sune A. , Olsen Niels T. , Marott Jacob L. , Schnohr Peter , Goetze Jens P. , Jensen Jan S.
Published: May 2009

Background—

Tissue Doppler imaging (TDI) detects left ventricular dysfunction in patients with heart failure and normal ejection fraction, but the prognostic significance of left ventricular dysfunction by TDI in the general population is unknown.

Methods and Results—

Within the Copenhagen City Heart Study, a large community-based population study, cardiac function was evaluated in 1036 participants by both conventional echocardiography and TDI. Averages of peak systolic (s′), early diastolic (e′), and late diastolic (a′) velocities from 6 mitral annular sites were used. TDI was furthermore quantified by a combined index (eas index) of diastolic and systolic performance: e′/(a′×s′). During follow-up (median, 5.3 years), 90 participants died. Left ventricular dysfunction by TDI, in terms of low s′ (hazard ratio, 1.23 per 1-cm/s decrease;
P
<0.05) and a′ (hazard ratio, 1.20 per 1-cm/s decrease;
P
=0.001), were significant predictors of death in Cox proportional-hazards models adjusted for clinical variables (age, sex, body mass index, heart rate, hypertension, diabetes mellitus, and ischemic heart disease) and conventional echocardiography. The adjusted hazard ratio for death in the third tertile compared with the first tertile of the combined index of systolic and diastolic performance by TDI was 2.5 (
P
<0.005).

Conclusions—

In the general population, in which most are free of left ventricular systolic dysfunction and restrictive diastolic filling using conventional echocardiographic parameters, left ventricular dysfunction by TDI is a powerful and independent predictor of death, especially when systolic performance and diastolic performance are considered together, recognizing their interdependency and their complex relation to deteriorating cardiac function.
Effects of Neuronal Nitric Oxide Synthase on Human Coronary Artery Diameter and Blood Flow In Vivo
Authors: Seddon Michael , Melikian Narbeh , Dworakowski Rafal , Shabeeh Husain , Jiang Benyu , Byrne Jonathan , Casadei Barbara , Chowienczyk Philip , Shah Ajay M.
Published: May 2009

Background—

Nitric oxide (NO)–mediated local regulation of vascular tone is considered to involve endothelial NO synthase (eNOS). However, we recently reported that human forearm basal microvascular tone in vivo is tonically regulated by neuronal NO synthase (nNOS), in contrast to an acetylcholine-stimulated reduction in tone, which is eNOS dependent. Here, we investigated the in vivo effects of an nNOS-selective inhibitor, S-methyl-
l
-thiocitrulline (SMTC), on the human coronary circulation and on flow-mediated dilatation in the forearm.

Methods and Results—

In patients with angiographically normal coronary arteries, intracoronary infusion of SMTC (0.625 μmol/min) reduced basal coronary blood flow by 34.1±5.2% (n=10;
P
<0.01) and epicardial coronary diameter by 3.6±1.2% (
P
=0.02) but had no effect on increases in flow evoked by intracoronary substance P (20 pmol/min). The nonselective NOS inhibitor
N
G
-monomethyl-
l
-arginine (25 μmol/min) also reduced basal coronary flow (by 22.3±5.3%; n=8;
P
<0.01) but, in contrast to SMTC, inhibited substance P–induced increases in flow (
P
<0.01). In healthy volunteers, local infusion of SMTC (0.2 μmol/min) reduced radial artery blood flow by 36.0±6.4% (n=10;
P
=0.03) but did not affect flow-mediated dilatation (
P
=0.55). In contrast,
N
G
-monomethyl-
l
-arginine (2 μmol/min) infusion reduced radial blood flow to a similar degree (by 39.7±11.8%;
P
=0.02) but also inhibited flow-mediated dilatation by ≈80% (
P
<0.01).

Conclusions—

These data indicate that local nNOS-derived NO regulates basal blood flow in the human coronary vascular bed, whereas substance P–stimulated vasodilatation is eNOS mediated. Thus, nNOS and eNOS have distinct local roles in the physiological regulation of human coronary vascular tone in vivo.
Lowering Plasma Cholesterol Levels Halts Progression of Aortic Valve Disease in Mice
Authors: Miller Jordan D. , Weiss Robert M. , Serrano Kristine M. , Brooks Robert M. , Berry Christopher J. , Zimmerman Kathy , Young Stephen G. , Heistad Donald D.
Published: May 2009

Background—

Treatment of hyperlipidemia produces functional and structural improvements in atherosclerotic vessels. However, the effects of treating hyperlipidemia on the structure and function of the aortic valve have been controversial, and any effects could be confounded by pleiotropic effects of hypolipidemic treatment. The goal of this study was to determine whether reducing elevated plasma lipid levels with a “genetic switch” in Reversa mice (
Ldlr
−/−/

Apob
100/100

/

Mttp
fl/fl

/Mx1-

Cre
+/+

) reduces oxidative stress, reduces pro-osteogenic signaling, and retards the progression of aortic valve disease.

Methods and Results—

After 6 months of hypercholesterolemia, Reversa mice exhibited increases in superoxide, lipid deposition, myofibroblast activation, calcium deposition, and pro-osteogenic protein expression in the aortic valve. Maximum aortic valve cusp separation, as judged by echocardiography, was not altered. During an additional 6 months of hypercholesterolemia, superoxide levels, valvular lipid deposition, and myofibroblast activation remained elevated. Furthermore, calcium deposition and pro-osteogenic gene expression became more pronounced, and the aortic cusp separation decreased from 0.85±0.04 to 0.70±0.04 mm (mean±SE;
P
<0.05). Rapid normalization of cholesterol levels at 6 months of age (by inducing expression of
Cre
recombinase) normalized aortic valve superoxide levels, decreased myofibroblast activation, reduced valvular calcium burden, suppressed pro-osteogenic signaling cascades, and prevented reductions in aortic valve cusp separation.

Conclusions—

Collectively, these data indicate that reducing plasma lipid levels by genetic inactivation of the
mttp
gene in hypercholesterolemic mice with early aortic valve disease normalizes oxidative stress, reduces pro-osteogenic signaling, and halts the progression of aortic valve stenosis.
Adenosine Contributes to Blood Flow Regulation in the Exercising Human Leg by Increasing Prostaglandin and Nitric Oxide Formation
Authors: Mortensen Stefan P. , Nyberg Michael , Thaning Pia , Saltin Bengt , Hellsten Ylva
Published: May 2009

Adenosine can induce vasodilation in skeletal muscle, but to what extent adenosine exerts its effect via formation of other vasodilators and whether there is redundancy between adenosine and other vasodilators remain unclear. We tested the hypothesis that adenosine, prostaglandins, and NO act in synergy to regulate skeletal muscle hyperemia by determining the following: (1) the effect of adenosine receptor blockade on skeletal muscle exercise hyperemia with and without simultaneous inhibition of prostaglandins (indomethacin; 0.8 to 1.8 mg/min) and NO (
N
G
-mono-methyl-
l
-arginine; 29 to 52 mg/min); (2) whether adenosine-induced vasodilation is mediated via formation of prostaglandins and/or NO; and (3) the femoral arterial and venous plasma adenosine concentrations during leg exercise with the microdialysis technique in a total of 24 healthy, male subjects. Inhibition of adenosine receptors (theophylline; 399±9 mg, mean ± SEM) or combined inhibition of prostaglandins and NO formation inhibited the exercise-induced increase in leg blood flow by 14±1% and 29±2% (
P
<0.05), respectively, but combined inhibition of prostaglandins, NO, and adenosine receptors did not result in an additive reduction of leg blood flow (31±5%). Femoral arterial infusion of adenosine increased leg blood flow from ≈0.3 to ≈2.5 L/min. Inhibition of prostaglandins or NO, or prostaglandins and NO combined, inhibited the adenosine-induced increase in leg blood flow by 51±3%, 39±8%, and 66±8%, respectively (
P
<0.05). Arterial and venous plasma adenosine concentrations were similar at rest and during exercise. These results suggest that adenosine contributes to the regulation of skeletal muscle blood flow by stimulating prostaglandin and NO synthesis.
“So We Die before Our Own Eyes”: Willful Sterility in The Country of the Pointed Firs
Authors: Jackson Holly
Published: May 2009

This essay locates Sarah Orne Jewett's The Country of the Pointed Firs in relation to contemporaneous sociological discourse decrying New England's diminished birthrate as a harbinger of national decline. Jewett's pairing of nativist nostalgia with a progressive vision of women's independence illuminates the conflicting demands of white nationalism and feminism in Roosevelt's America.
“And Do Not Forget Emily”: Con{f}idante Abby Wood on Dickinson's Lonely Religious Rebellion
Authors: Longsworth Polly
Published: May 2009

Confidante Abby Wood describes Emily Dickinson's tortured mind during the Great Revival of 1850. “She treated me as if she were insane,” Abby writes after a call. “The spirit of God is striving in her bosom and she is perfectly wretched.” While Wood is converted, Dickinson “grieves away” her opportunity.
Computational Cost and Accuracy in Calculating Three-Dimensional Radiative Transfer: Results for New Implementations of Monte Carlo and SHDOM
Authors: Pincus Robert , Evans K. Franklin
Published: May 2009

This paper examines the tradeoffs between computational cost and accuracy for two new state-of-the-art codes for computing three-dimensional radiative transfer: a community Monte Carlo model and a parallel implementation of the Spherical Harmonics Discrete Ordinate Method (SHDOM). Both codes are described and algorithmic choices are elaborated. Two prototype problems are considered: a domain filled with stratocumulus clouds and another containing scattered shallow cumulus, absorbing aerosols, and molecular scatterers. Calculations are performed for a range of resolutions and the relationships between accuracy and computational cost, measured by memory use and time to solution, are compared.

Monte Carlo accuracy depends primarily on the number of trajectories used in the integration. Monte Carlo estimates of intensity are computationally expensive and may be subject to large sampling noise from highly peaked phase functions. This noise can be decreased using a range of variance reduction techniques, but these techniques can compromise the excellent agreement between the true error and estimates obtained from unbiased calculations. SHDOM accuracy is controlled by both spatial and angular resolution; different output fields are sensitive to different aspects of this resolution, so the optimum accuracy parameters depend on which quantities are desired as well as on the characteristics of the problem being solved. The accuracy of SHDOM must be assessed through convergence tests and all results from unconverged solutions may be biased.

SHDOM is more efficient (i.e., has lower error for a given computational cost) than Monte Carlo when computing pixel-by-pixel upwelling fluxes in the cumulus scene, whereas Monte Carlo is more efficient in computing flux divergence and downwelling flux in the stratocumulus scene, especially at higher accuracies. The two models are comparable for downwelling flux and flux divergence in cumulus and upwelling flux in stratocumulus. SHDOM is substantially more efficient when computing pixel-by-pixel intensity in multiple directions; the models are comparable when computing domain-average intensities. In some cases memory use, rather than computation time, may limit the resolution of SHDOM calculations.
In-Flight Spectral Characterization and Calibration Stability Estimates for the Clouds and the Earth’s Radiant Energy System (CERES)
Authors: Matthews Grant
Published: May 2009

It is essential to maintain global measurements of the earth radiation budget (ERB) from space, the scattered solar and emitted thermal radiative fluxes leaving the planet. These are required for the purpose of validating current climate model predictions of the planet’s future response to anthropogenic greenhouse gas forcing. The measurement accuracy and calibration stability required to resolve the magnitude of model-suggested cloud–climate feedbacks on the ERB have recently been estimated. The suggestion is for ERB data to strive for a calibration stability of ±0.3% decade−1 for scattered solar, ±0.5% decade−1 for emitted thermal, and an overall absolute accuracy of 1 W m−2. The Clouds and the Earth’s Radiant Energy System (CERES) is currently the only satellite program to make global ERB measurements, beginning in January 1998. However, the new climate calibration standards are beyond those originally specified by the NASA CERES program for its edition 2 data release. Furthermore, the CERES instrument optics have been discovered to undergo substantial in-flight degradation because of contaminant issues. This is not directly detectable by using established calibration methods. Hence, user-applied revisions for edition 2 shortwave (SW) data were derived to compensate for this effect, which is described as “spectral darkening.” Also, an entirely new in-flight calibration protocol has been developed for CERES that uses deep convective cloud albedo as a primary solar wavelength stability metric. This is then combined with a sophisticated contamination mobilization/polymerization model. The intention is to assign spectral coloration to any optical degradation occurring to the different CERES Earth observing telescopes. This paper quantifies the stability of revised edition 2 data. It also calculates stability, which the new protocols could give CERES measurements if used. The conclusion is that the edition 2 revisions restore the originally specified stability of CERES SW data. It is also determined that the climate calibration stability goals are reachable by using the new in-flight methodologies presented in this paper. However, this will require datasets of longer than approximately 10 yr. It will also require obtaining regular raster scans of the Moon by all operational CERES instruments.
Maternal Interactional Quality in Two Cultural Environments
Authors: Yovsi Relindis D. , Kärtner Joscha , Keller Heidi , Lohaus Arnold
Published: May 2009

This study compares German urban middle class with Cameroonian rural Nso mothers interacting with their 4-, 8-, and 12-week-olds on two dimensions of parenting: sensitivity and responsive control. Although the first concept is well-established in the literature, we suggest responsive control as the essence of good parenting leading to optimal development according to Nso mothers' ethnotheories. Although the two concepts differentiate between the two samples, the validity of responsive control in terms of developmental implications still has to be established.
Options to Improve Livelihoods and Protect Natural Resources in Dry Environments
Authors: La Rovere Roberto , Bruggeman Adriana , Turkelboom Francis , Aw-Hassan Aden , Thomas Richard , Al-Ahmad Kasem
Published: May 2009

This article reviews work that had the objective of introducing agricultural technologies in a marginal dryland area, the Khanasser Valley, northwestern Syria. The highly variable rainfall is barely sufficient to support livelihoods in this traditional barley—livestock production system. The valley is representative of other marginal dryland areas in West Asia and North Africa. We used a farmer-participatory approach to evaluate the performance of agricultural technologies for dry marginal areas in terms of their contribution to livelihoods and effect on the environment. The integrated approach allowed comprehensively comparing and evaluating the viability of promising technologies, including novel crops, intercropping, soil management techniques, and livestock rearing. The results show that improved barley varieties, olives, cumin, and lamb fattening can improve livelihoods, particularly for the land-owning households, whereas other households can benefit indirectly in terms of employment spillovers. These options are also environmentally friendly and sustain the natural resource base.
Propofol Protects Against Hemorrhagic Shock-Induced Organ Damage in Conscious Spontaneously Hypertensive Rats
Authors: Lee Chung-Jen , Lee Ru-Ping , Subeq Yi-Maun , Lee Chia-Chi , Peng Tai-Chu , Hsu Bang-Gee
Published: May 2009

Patients with hypertension have higher mortality rates from hemorrhagic shock (HS) than normotensive patients. Several inflammatory mediators such as tumor necrosis factor a (TNF-a) and interleukin 10 (IL-10) can be produced by HS and lead to multiple organ dysfunction and death. We investigated the effects of high dose (10 mg/kg/hr) and low dose (1 mg/kg/hr) propofol treatment after HS in conscious spontaneously hypertensive rats (SHRs). By withdrawing 40% of total blood volume from a femoral arterial catheter (6 ml/100 g body weight [BW]) for more than 30 min, HS was induced. The mean arterial pressure (MAP) and heart rate (HR) were monitored continuously for 24 hr after the start of blood withdrawal. Levels of biochemical parameters, including glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine (Cre), creatine phosphokinase (CPK), and lactic dehydrogenase (LDH) were measured 30 min before and 0, 1, 3, 6, 9, 12, 18, and 24 hr after the 30-min blood withdrawal period. Cytokine levels, including TNF-a and IL-10 in the serum, were measured 1 hr after HS. The kidney, liver, and lung were removed for pathology assessment at 48 hr after HS. HS significantly increased blood GOT, GPT, BUN, LDH, CPK, TNF-a, and IL-10 levels in conscious SHRs. Posttreatment propofol decreased serum TNF-a level, increased serum IL-10 level, attenuated the severity of organ damage, and improved survival rate after HS. This treatment protected SHRs against HS-induced organ damage. Moreover, high-dose propofol had a more protective effect than low-dose propofol against HS in conscious SHRs.
Modelling zero-inflated spatio-temporal processes
Authors: Fernandes Marcus VM , Schmidt Alexandra M , Migon Helio S
Published: May 2009

We consider models for spatio-temporal processes which assume either non-negative values, and often are observed as zero, or discrete values and are also inflated by zeros. Typically, in the first case, the spatial observations are obtained at fixed locations (point-referenced data) over a region D; whereas in the second, the region D is divided into a finite number of regular or irregular subregions (areal level), resulting in observations for each subregion. Our main idea is based on those of zeroinflated models, by assuming that the value observed at location s and time t, Yt (s), is a realization of a mixture between a Bernoulli distribution with a probability of success θt (s) and a probability density function or probability function p( yt (s) | .) For both cases, we include spatio-temporal latent processes in the model to account for the possible extra variation present in the mean structure of θt (s) and/or p(yt(s) | .). In the context of point-referenced data, we model the amount of rainfall over the city of Rio de Janeiro during 75 weeks; whereas in the areal data level case, we consider weekly cases of dengue fever in the city of Rio de Janeiro during the years of 2001–02.
Punctuating the home page: image as language in an online newspaper
Authors: Knox John S.
Published: May 2009

Between February 2002 and April 2006, the Sydney Morning Herald online [www.smh.com.au], an influential Australian newspaper which went online in 1995, showed a remarkable degree of change in the design of its home page. However, over the same time period, the use of images in hard-news stories on its home page was remarkably consistent, both diachronically and synchronically. These hard-news images are small `thumbnails', and are most typically close crops of faces. Their small size, their consistent and limited subject matter, and their positioning in news stories represent a new practice in hard-news reporting, and raise questions about the role they play in the multimodal story-telling practices of the newspaper, and about the discursive practices of online newspapers more generally. This article presents an analysis of these thumbnails using tools from systemic functional semiotics, and an investigation from three socio-historical perspectives (news photography, typography, and punctuation). On this basis, I argue that in the specific discursive context of the home page of the Sydney Morning Herald online during the time period studied, thumbnails function less as images and more as an expression of the expanding system of language in computer-mediated communication.
Estimating parameters for generalized mass action models with connectivity information
Authors: Ko Chih-Lung , Voit Eberhard O , Wang Feng-Sheng
Published: May 2009

Background

Determining the parameters of a mathematical model from quantitative measurements is the main bottleneck of modelling biological systems. Parameter values can be estimated from steady-state data or from dynamic data. The nature of suitable data for these two types of estimation is rather different. For instance, estimations of parameter values in pathway models, such as kinetic orders, rate constants, flux control coefficients or elasticities, from steady-state data are generally based on experiments that measure how a biochemical system responds to small perturbations around the steady state. In contrast, parameter estimation from dynamic data requires time series measurements for all dependent variables. Almost no literature has so far discussed the combined use of both steady-state and transient data for estimating parameter values of biochemical systems.

Results

In this study we introduce a constrained optimization method for estimating parameter values of biochemical pathway models using steady-state information and transient measurements. The constraints are derived from the flux connectivity relationships of the system at the steady state. Two case studies demonstrate the estimation results with and without flux connectivity constraints. The unconstrained optimal estimates from dynamic data may fit the experiments well, but they do not necessarily maintain the connectivity relationships. As a consequence, individual fluxes may be misrepresented, which may cause problems in later extrapolations. By contrast, the constrained estimation accounting for flux connectivity information reduces this misrepresentation and thereby yields improved model parameters.

Conclusion

The method combines transient metabolic profiles and steady-state information and leads to the formulation of an inverse parameter estimation task as a constrained optimization problem. Parameter estimation and model selection are simultaneously carried out on the constrained optimization problem and yield realistic model parameters that are more likely to hold up in extrapolations with the model.
A network-based integrative approach to prioritize reliable hits from multiple genome-wide RNAi screens in Drosophila
Authors: Wang Li , Tu Zhidong , Sun Fengzhu
Published: May 2009

Background

The recently developed RNA interference (RNAi) technology has created an unprecedented opportunity which allows the function of individual genes in whole organisms or cell lines to be interrogated at genome-wide scale. However, multiple issues, such as off-target effects or low efficacies in knocking down certain genes, have produced RNAi screening results that are often noisy and that potentially yield both high rates of false positives and false negatives. Therefore, integrating RNAi screening results with other information, such as protein-protein interaction (PPI), may help to address these issues.

Results

By analyzing 24 genome-wide RNAi screens interrogating various biological processes in Drosophila, we found that RNAi positive hits were significantly more connected to each other when analyzed within a protein-protein interaction network, as opposed to random cases, for nearly all screens. Based on this finding, we developed a network-based approach to identify false positives (FPs) and false negatives (FNs) in these screening results. This approach relied on a scoring function, which we termed NePhe, to integrate information obtained from both PPI network and RNAi screening results. Using a novel rank-based test, we compared the performance of different NePhe scoring functions and found that diffusion kernel-based methods generally outperformed others, such as direct neighbor-based methods. Using two genome-wide RNAi screens as examples, we validated our approach extensively from multiple aspects. We prioritized hits in the original screens that were more likely to be reproduced by the validation screen and recovered potential FNs whose involvements in the biological process were suggested by previous knowledge and mutant phenotypes. Finally, we demonstrated that the NePhe scoring system helped to biologically interpret RNAi results at the module level.

Conclusion

By comprehensively analyzing multiple genome-wide RNAi screens, we conclude that network information can be effectively integrated with RNAi results to produce suggestive FPs and FNs, and to bring biological insight to the screening results.
Measuring differential gene expression by short read sequencing: quantitative comparison to 2-channel gene expression microarrays
Authors: Bloom Joshua S , Khan Zia , Kruglyak Leonid , Singh Mona , Caudy Amy A
Published: May 2009

Background

High-throughput cDNA synthesis and sequencing of poly(A)-enriched RNA is rapidly emerging as a technology competing to replace microarrays as a quantitative platform for measuring gene expression.

Results

Consequently, we compared full length cDNA sequencing to 2-channel gene expression microarrays in the context of measuring differential gene expression. Because of its comparable cost to a gene expression microarray, our study focused on the data obtainable from a single lane of an Illumina 1 G sequencer. We compared sequencing data to a highly replicated microarray experiment profiling two divergent strains of S. cerevisiae.

Conclusion

Using a large number of quantitative PCR (qPCR) assays, more than previous studies, we found that neither technology is decisively better at measuring differential gene expression. Further, we report sequencing results from a diploid hybrid of two strains of S. cerevisiae that indicate full length cDNA sequencing can discover heterozygosity and measure quantitative allele-specific expression simultaneously.
Paracoccidioides brasiliensis pancreatic destruction in Calomys callosusexperimentally infected
Authors: Fortes Rogério M , Kipnis André , Junqueira-Kipnis Ana Paula
Published: May 2009

Background

The wild rodent Calomys callosus is notably resistant to Trypanosoma cruzi infection. In order to better characterize this animal model for experimental infections, we inoculated C. callosus intraperitoneally with Paracoccidioides brasiliensis, a thermally dimorphic fungus that causes a chronic disease with severe granuloma formation in the mouse and humans. The dissemination of P. brasiliensis cells through the lungs, liver, pancreas, and spleen was assessed by histological analysis.

Results

The animals were susceptible to infection and showed a granulomatous reaction. C. callosus presented peritonitis characterized by the presence of exudates containing a large number of yeast cells. Extensive accumulation of yeast cells with intense destruction of the parenchyma was observed in the pancreas, which reduced the glucose levels of infected animals. These lesions were regressive in the liver, spleen, and lungs until complete recovery. The role of estrogen during C. callosus infection with P. brasiliensis was addressed by infecting ovariectomized animals. It was observed a reduced inflammatory response as well as reduced extension of tissue damage. Removal of ovaries reestablished the normal glucose levels during infection.

Conclusion

Taken together, the results presented here reveal the pancreas as being an important organ for the persistence of P. brasiliensis during infection of C. callosus and that estrogen plays an important role in the susceptibility of the animals to this pathogen.
Revised Mimivirus major capsid protein sequence reveals intron-containing gene structure and extra domain
Authors: Azza Saïd , Cambillau Christian , Raoult Didier , Suzan-Monti Marie
Published: May 2009

Background

Acanthamoebae polyphaga Mimivirus (APM) is the largest known dsDNA virus. The viral particle has a nearly icosahedral structure with an internal capsid shell surrounded with a dense layer of fibrils. A Capsid protein sequence, D13L, was deduced from the APM L425 coding gene and was shown to be the most abundant protein found within the viral particle. However this protein remained poorly characterised until now. A revised protein sequence deposited in a database suggested an additional N-terminal stretch of 142 amino acids missing from the original deduced sequence. This result led us to investigate the L425 gene structure and the biochemical properties of the complete APM major Capsid protein.

Results

This study describes the full length 3430 bp Capsid coding gene and characterises the 593 amino acids long corresponding Capsid protein 1. The recombinant full length protein allowed the production of a specific monoclonal antibody able to detect the Capsid protein 1 within the viral particle. This protein appeared to be post-translationnally modified by glycosylation and phosphorylation. We proposed a secondary structure prediction of APM Capsid protein 1 compared to the Capsid protein structure of Paramecium Bursaria Chlorella Virus 1, another member of the Nucleo-Cytoplasmic Large DNA virus family.

Conclusion

The characterisation of the full length L425 Capsid coding gene of Acanthamoebae polyphaga Mimivirus provides new insights into the structure of the main Capsid protein. The production of a full length recombinant protein will be useful for further structural studies.
Reducing stillbirths: prevention and management of medical disorders and infections during pregnancy
Authors: Menezes Esme V , Yakoob Mohammad Yawar , Soomro Tanya , Haws Rachel A , Darmstadt Gary L , Bhutta Zulfiqar A
Published: May 2009

Background

An estimated two-thirds of the world's 3.2 million stillbirths occur antenatally, prior to labour, and are often overlooked in policy and programs. Poorly recognised, untreated or inadequately treated maternal infections such as syphilis and malaria, and maternal conditions including hypertensive disorders, are known risk factors for stillbirth.

Methods

We undertook a systematic review of the evidence for 16 antenatal interventions with the potential to prevent stillbirths. We searched a range of sources including PubMed and the Cochrane Library. For interventions with prior Cochrane reviews, we conducted additional meta-analyses including eligible newer randomised controlled trials following the Cochrane protocol. We focused on interventions deliverable at the community level in low-/middle-income countries, where the burden of stillbirths is greatest.

Results

Few of the studies we included reported stillbirth as an outcome; most that did were underpowered to assess this outcome. While Cochrane reviews or meta-analyses were available for many interventions, few focused on stillbirth or perinatal mortality as outcomes, and evidence was frequently conflicting. Several interventions showed clear evidence of impact on stillbirths, including heparin therapy for certain maternal indications; syphilis screening and treatment; and insecticide-treated bed nets for prevention of malaria. Other interventions, such as management of obstetric intrahepatic cholestasis, maternal anti-helminthic treatment, and intermittent preventive treatment of malaria, showed promising impact on stillbirth rates but require confirmatory studies. Several interventions reduced known risk factors for stillbirth (e.g., anti-hypertensive drugs for chronic hypertension), yet failed to show statistically significant impact on stillbirth or perinatal mortality rates. Periodontal disease emerged as a clear risk factor for stillbirth but no interventions have reduced stillbirth rates.

Conclusion

Evidence for some newly recognised risk factors for stillbirth, including periodontal disease, suggests the need for large, appropriately designed randomised trials to test whether intervention can minimise these risks and prevent stillbirths. Existing evidence strongly supports infection control measures, including syphilis screening and treatment and malaria prophylaxis in endemic areas, for preventing antepartum stillbirths. These interventions should be incorporated into antenatal care programs based on attributable risks and burden of disease.
Tracking the global dispersal of a cosmopolitan insect pest, the peach potato aphid
Authors: Margaritopoulos John T , Kasprowicz Louise , Malloch Gaynor L , Fenton Brian
Published: May 2009

Background

Global commerce and human transportation are responsible for the range expansion of various insect pests such as the plant sucking aphids. High resolution DNA markers provide the opportunity to examine the genetic structure of aphid populations, identify aphid genotypes and infer their evolutionary history and routes of expansion which is of value in developing management strategies. One of the most widespread aphid species is the peach-potato aphid Myzus persicae, which is considered as a serious pest on various crops in many parts of the world. The present study examined the genetic variation of this aphid at a world scale and then related this to distribution patterns. In particular, 197 aphid parthenogenetic lineages from around the world were analysed with six microsatellite loci.

Results

Bayesian clustering and admixture analysis split the aphid genotypes into three genetic clusters: European M. persicae persicae, New Zealand M. persicae persicae and Global M. persicae nicotianae. This partition was supported by F
ST and genetic distance analyses. The results showed two further points, a possible connection between genotypes found in the UK and New Zealand and globalization of nicotianae associated with colonisation of regions where tobacco is not cultivated. In addition, we report the presence of geographically widespread clones and for the first time the presence of a nicotianae genotype in the Old and New World. Lastly, heterozygote deficiency was detected in some sexual and asexual populations.

Conclusion

The study revealed important genetic variation among the aphid populations we examined and this was partitioned according to region and host-plant. Clonal selection and gene flow between sexual and asexual lineages are important factors shaping the genetic structure of the aphid populations. In addition, the results reflected the globalization of two subspecies of M. persicae with successful clones being spread at various scales throughout the world. A subspecies appears to result from direct selection on tobacco plants. This information highlights the ultimate ability of a polyphagous aphid species to generate and maintain ecologically successful gene combinations through clonal propagation and the role of human transportation and global commerce for expanding their range.