bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti‐HIV adaptive immunity: determinants for viral persistence
Authors: Yamamoto Hiroyuki , Matano Tetsuro
Published: April 2008

The immense difficulty in primary control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection by adaptive immune responses has been a topic of exceptional importance. CD8+ cytotoxic T lymphocytes (CTLs) do play a central role in primary resolution of viremia, but their potency in viral control is generally constrained in the natural courses of HIV/SIV infections. The overall repertoire of CTLs is dependent on both the host and the virus genetic polymorphisms, and the potency of each individual CTL is affected by immunological and virological determinants. HIV/SIV infections lack early appearance of neutralising antibodies (NAbs), and our recent finding has suggested a possibility of their absence contributing to diminished virus‐specific CD4+ T‐cell responses leading to failure in primary viral control. Extrapolations from studies in macaque models of SIV infection and analyses of the cohorts of HIV control in humans have to date delineated the numerous requirements for attainment of viral control. Understanding of the individual components of adaptive immune responses and their optimal concert required for HIV/SIV control would contribute to development of an effective AIDS vaccine. Here, we discuss current insights into CTLs and NAbs, and speculate their possible protective mechanism against establishment of persistent HIV/SIV infection. Copyright © 2008 John Wiley & Sons, Ltd.
Joint spatial survival modeling for the age at diagnosis and the vital outcome of prostate cancer
Authors: Zhou Huafeng , Lawson Andrew B. , Hebert James R. , Slate Elizabeth H. , Hill Elizabeth G.
Published: April 2008

Prostate cancer (PrCA) is the most common malignancy in men and a leading cause of cancer mortality among males in the United States. Large geographical variation and racial disparities exist in both the incidence of PrCA and the survival rate after diagnosis. In this population‐based study, a joint spatial survival model is constructed to investigate factors that affect the age at diagnosis of PrCA and the subsequent survival. The joint model for these two time‐to‐event outcomes is specified through parametric models for age at diagnosis and survival time conditional on diagnosis age. To account for possible correlation in these outcomes among men from the same geographical region, frailty terms are included in the survival model. Both spatially correlated and uncorrelated frailties are incorporated in each model considered. The deviance information criterion is used to select a best‐fitting model within the Bayesian framework. The results from our final best‐fitting model indicate that race, marital status at diagnosis, and cancer stage are significantly associated with both of the two time‐to‐event outcomes. No pattern emerged in the geographical distribution of age at PrCA diagnosis. In contrast, a spatially clustered pattern was observed in the geographic distribution of survival experience post diagnosis. Copyright © 2008 John Wiley & Sons, Ltd.
Measurement error correction for nutritional exposures with correlated measurement error: Use of the method of triads in a longitudinal setting
Authors: Rosner Bernard , Michels Karin B. , Chen Ya‐Hua , Day Nicholas E.
Published: April 2008

Nutritional exposures are often measured with considerable error in commonly used surrogate instruments such as the food frequency questionnaire (FFQ) (denoted by Qi for the ith subject). The error can be both systematic and random. The diet record (DR) denoted by Ri for the ith subject is considered an alloyed gold standard. However, some authors have reported both systematic and random errors with this instrument as well.

One goal in measurement error research is to estimate the regression coefficient of Ti (true intake for the ith subject) on Qi denoted by λTQ. If the systematic errors in Qi and Ri (denoted by qi and ri) are uncorrelated, then one can obtain an unbiased estimate of λTQ by λRQ obtained by regressing Ri on Qi. However, if Corr(qi, ri)>0, then λRQ>λTQ.

In this paper, we propose a method for indirectly estimating λTQ even in the presence of correlated systematic error based on a longitudinal design where Qi (surrogate measure of dietary intake), Ri (a reference measure of dietary intake), and Mi (a biomarker) are available on the same subjects at 2 time points. In addition, between‐person variation in mean levels of Mi among people with the same dietary intake is also accounted for. The methodology is illustrated for dietary vitamin C intake based on longitudinal data from 323 subjects in the European Prospective Investigation of Cancer (EPIC)‐Norfolk study who provided two measures of dietary vitamin C intake from the FFQ (Qi) and a 7‐day DR (Ri) and plasma vitamin C (Mi) 4 years apart. Copyright © 2008 John Wiley & Sons, Ltd.
Sample size for equivalence trials: A case study from a vaccine lot consistency trial
Authors: Ganju Jitendra , Izu Allen , Anemona Alessandra
Published: April 2008

For some trials, simple but subtle assumptions can have a profound impact on the size of the trial. A case in point is a vaccine lot consistency (or equivalence) trial. Standard sample size formulas used for designing lot consistency trials rely on only one component of variation, namely, the variation in antibody titers within lots. The other component, the variation in the means of titers between lots, is assumed to be equal to zero. In reality, some amount of variation between lots, however small, will be present even under the best manufacturing practices. Using data from a published lot consistency trial, we demonstrate that when the between‐lot variation is only 0.5 per cent of the total variation, the increase in the sample size is nearly 300 per cent when compared with the size assuming that the lots are identical. The increase in the sample size is so pronounced that in order to maintain power one is led to consider a less stringent criterion for demonstration of lot consistency. The appropriate sample size formula that is a function of both components of variation is provided. We also discuss the increase in the sample size due to correlated comparisons arising from three pairs of lots as a function of the between‐lot variance. Copyright © 2008 John Wiley & Sons, Ltd.
Modern management of amenorrhoea
Authors: Maruthini Deivanayagam , Balen Adam
Published: April 2008

It is essential to differentiate between an oestrogen‐deficient state and an adequate or surplus state to define an holistic approach to the treatment of amenorrhoea. The authors summarise the initial assessment, investigations and management options for primary and secondary amenorrhoea. Copyright © 2008 Wiley Interface Ltd
ROCK and PRK‐2 mediate the inhibitory effect of Y‐27632 on polyglutamine aggregation
Authors: Shao Jieya , Welch William J. , Diamond Marc I.
Published: April 2008

Polyglutamine expansion in huntingtin (Htt) and the androgen receptor (AR) causes untreatable neurodegenerative diseases. Y‐27632, a therapeutic lead, reduces Htt and AR aggregation in cultured cells, and Htt‐induced neurodegeneration in Drosophila. Y‐27632 inhibits both Rho‐associated kinases ROCK and PRK‐2, making its precise intracellular target uncertain. Over‐expression of either kinase increases Htt and AR aggregation. Three ROCK inhibitors (Y‐27632, HA‐1077, and H‐1152P), and a specific ROCK inhibitory peptide reduce polyglutamine protein aggregation, as does knockdown of ROCK or PRK‐2 by RNAi. RNAi also indicates that each kinase is required for the inhibitory effects of Y‐27632 to manifest fully. These two actin regulatory kinases are thus involved in polyglutamine aggregation, and their simultaneous inhibition may be an important therapeutic goal.
Neuropeptide Y expression in vaginal epithelium of women with pelvic organ prolapse and stress urinary incontinence
Authors: Zhu Lan , Lang Jinghe , Jiang Xueying , Jiang Fang , Chen Jie , Wong Felix
Published: April 2008

Objectives

To determine the role of neuropeptide Y (NPY) in anterior and posterior vaginal epithelium in the etiologic development of pelvic organ prolapse (POP) and stress urinary incontinence (SUI).

Methods

Forty biopsy specimens from anterior and posterior vaginal epithelium were obtained from 40 POP/SUI patients and controls. The specimens were stained using hematoxylin and eosin and NPY immunohistochemical staining. NPY was measured semiquantitatively and NPY mRNA expression was assessed using DNA hybridization in situ.

Results

There were no significant differences in NPY between anterior and posterior vaginal epithelium. NPY profiles in posterior vaginal epithelium in the SUI group were significantly lower than in the POP (P < 0.05) and control (P < 0.05) groups. In the POP group, the NPY profile correlated negatively with advancing age and years post menopause.

Conclusion

The reduction in NPY in the anterior and posterior vaginal wall epithelium might be related to nerve damage or degeneration, resulting in a change in blood flow, atrophy, and pelvic floor laxity in patients with POP and SUI, especially post menopause and with advancing age.
Pensée 2: Egregious Abuses Warrant a Boycott
Authors: Bisharat George
Published: April 2008

Recent calls to boycott Israel, including its academic institutions, have stimulated heated debate over the relationship between boycotts and academic freedom. Academic boycotts admittedly raise complex issues, as they typically trammel academic freedom to some degree. Nonetheless, I do not favor a blanket refusal to engage in them. Although applying a negative presumption, we should consider academic boycotts on a case-by-case basis.
EMPIRE AND THE HAJJ: PILGRIMS, PLAGUES, AND PAN-ISLAM UNDER BRITISH SURVEILLANCE, 1865–1908
Authors: Low Michael Christopher
Published: April 2008

From the mid-19th to the early 20th centuries, the forces unleashed by the age of European imperialism and its rapid encroachment ondār al-Islāmincreasingly brought the hajj under the scrutiny and regulation of non-Muslim powers. The driving force behind these dramatic changes in administration of the hajj was the expansion of the British Empire. As Britain's power in the Indian subcontinent grew, so too did its maritime supremacy throughout the Indian Ocean basin. Looking to secure its access to India, ward off its European competitors, and expand its commercial interests in southwestern Arabia, the Red Sea, and the Gulf of Aden, Britain's role in the region was intensified by the transit opportunities that emerged with the development of regular steamship routes between the Mediterranean and India from the 1830s to the 1860s and the eventual opening of the Suez Canal in 1869. With the exponential growth of maritime traffic that accompanied these technological advances came a similarly dramatic rise in the oceangoing pilgrim traffic from and through British India. Owing to this expansion in the number of seaborne pilgrims, the hajj soon came to be recognized as the primary conduit for the globalization of epidemic diseases, such as cholera and plague.
Trimodal cloudiness and tropical stable layers in simulations of radiative convective equilibrium
Authors: Posselt D. J. , van den Heever S. C. , Stephens G. L.
Published: April 2008

In this paper, we examine the tropical environment at radiative convective equilibrium using a large‐domain cloud system resolving numerical model. As in observed studies of convectively active periods over warm tropical oceans (in particular the tropical western Pacific), we find a trimodal cloud structure that is closely associated with the presence of three distinct stable layers, including a prominent stable layer located near the zero‐degree Celsius level. In addition, the simulation exhibits three separate large scale zonal overturning circulations, with two of these circulations located above the trade wind inversion and separated by the freezing level stable layer. At equilibrium, latent heat release associated with freezing and melting processes is dwarfed by that of vapor transitions, and simulation results suggest that this stable layer can be maintained by subsidence in the presence of longwave radiative cooling above the zero‐degree level.
Geotail and LFM comparisons of plasma sheet climatology: 1. Average values
Authors: Guild Timothy B. , Spence Harlan E. , Kepko E. Larry , Merkin Viacheslav , Lyon John G. , Wiltberger Michael , Goodrich Charles C.
Published: April 2008

We compare the statistics of central plasma sheet properties from 6 years of Geotail observations with 2 months of Lyon‐Fedder‐Mobarry (LFM) global MHD simulations. This statistical validation effort represents an inherently new method of systematically characterizing and quantifying global MHD model performance. For our comparison, we identify the central plasma sheet in the observations and simulation by identical criteria and select the simulation interval to ensure statistically similar distributions of solar wind conditions in both studies. After verifying our plasma sheet selection by inspecting the magnetic signatures of both studies, we compare the resultant number densities, thermal pressures, thermal energies, and bulk flows as functions of position across the equatorial plane. We find that the LFM model successfully reproduces the gross features of the global plasma sheet in a statistical sense. However, our comparison also reveals certain systematic discrepancies between the model and the observations. The LFM predicts a plasma sheet which is too dense, too cool, and exhibits faster globally averaged bulk flows than the observed plasma sheet. By quantifying the LFM overestimate of ionospheric transpolar potential and showing that ΦPC correlates with plasma sheet flow speed, we demonstrate that 15% of the plasma sheet velocity discrepancy is reflected in a ΦPC overestimate. This statistical validation effort represents an essential first step toward the rigorous, quantitative evaluation of a global MHD model in the plasma sheet.
Effect of 6‐Month Calorie Restriction and Exercise on Serum and Liver Lipids and Markers of Liver Function
Authors: Larson‐Meyer D. Enette , Newcomer Bradley R. , Heilbronn Leonie K. , Volaufova Julia , Smith Steven R. , Alfonso Anthony J. , Lefevre Michael , Rood Jennifer C. , Williamson Donald A. , Ravussin Eric ,   The Pennington CALERIE Team
Published: April 2008

Objective: Nonalcoholic fatty liver disease (NAFLD) and its association with insulin resistance are increasingly recognized as major health burdens. The main objectives of this study were to assess the relation between liver lipid content and serum lipids, markers of liver function and inflammation in healthy overweight subjects, and to determine whether caloric restriction (CR) (which improves insulin resistance) reduces liver lipids in association with these same measures.

Methods and Procedures: Forty‐six white and black overweight men and women (BMI = 24.7–31.3 kg/m2) were randomized to “control (CO)” = 100% energy requirements; “CR” = 25%; “caloric restriction and increased structured exercise (CR+EX)”= 12.5% CR + 12.5% increase in energy expenditure through exercise; or “low‐calorie diet (LCD)” = 15% weight loss by liquid diet followed by weight‐maintenance, for 6 months. Liver lipid content was assessed by magnetic resonance spectroscopy (MRS) and computed tomography (CT). Lipid concentrations, markers of liver function (alanine aminotransferase (ALT), alkaline phosphatase (ALK)), and whole‐body inflammation (tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), high‐sensitivity C‐reactive protein (hsCRP)) were measured in fasting blood.

Results: At baseline, increased liver lipid content (by MRS) correlated (P < 0.05) with elevated fasting triglyceride (r = 0.52), ALT (r = 0.42), and hsCRP (r = 0.33) concentrations after adjusting for sex, race, and alcohol consumption. With CR, liver lipid content was significantly lowered by CR, CR+EX, and LCD (detected by MRS only). The reduction in liver lipid content, however, was not significantly correlated with the reduction in triglycerides (r = 0.26; P = 0.11) or with the changes in ALT, high‐density lipoprotein (HDL)‐cholesterol, or markers of whole‐body inflammation.

Discussion: CR may be beneficial for reducing liver lipid and lowering triglycerides in overweight subjects without known NAFLD.
Effects of the New C1q/TNF‐related Protein (CTRP‐3) “Cartonectin” on the Adipocytic Secretion of Adipokines
Authors: Wölfing Britta , Buechler Christa , Weigert Johanna , Neumeier Markus , Aslanidis Charalampos , Schöelmerich Juergen , Schäffler Andreas
Published: April 2008

Background: Cartonectin (collagenous repeat‐containing sequence of 26‐kDa protein; CORS‐26) was described as a new adipokine of the C1q/TNF molecular superfamily C1q/TNF‐related protein‐3 (CTRP‐3), secreted by the adipocytes of mice and humans. The receptor and function of cartonectin are unknown and the recombinant protein is not commercially available.

Objective: To investigate the effects of recombinant cartonectin on the secretion of adipokines such as adiponectin, leptin, and resistin from adipocytes of human and murine origin. The effect of the BMI of the adipocyte donor was also investigated.

Methods and Procedures: Human adipocytes from pooled lean and preobese healthy individuals and murine 3T3‐L1 adipocytes were used for stimulation experiments. Recombinant cartonectin was expressed in insect H5 cells. Adipokine secretion was measured using enzyme‐linked immunosorbent assay. In addition, western blot analysis and luciferase reporter gene assays were employed.

Results: Cartonectin (1, 10, 50, and 250 ng/ml) in higher doses stimulates the secretion of adiponectin and resistin from murine adipocytes. This effect is not caused by an induction of peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) protein expression, as confirmed by western blot analysis. Also, luciferase reporter gene assay revealed that cartonectin failed to induce luciferase activity at the peroxisome proliferator‐activated receptor responsive element site containing the adiponectin/luciferase promoter fragment. Human adipocytes from lean individuals secrete higher amounts of adiponectin and leptin when compared with adipocytes of individuals with a preobesity BMI (25–30 kg/m2). Cartonectin failed to stimulate adiponectin or leptin secretion from human adipocytes, irrespective of the BMI value.

Discussion: Cartonectin is a new adipokine that differentially regulates the secretion of classical adipokines, with marked differences between the human and the murine systems. These effects are species‐dependent, while basal adipokine secretion is influenced by the BMI.
Physical Activity and Healthy Weight Maintenance From Childhood to Adulthood
Authors: Cleland Verity J. , Dwyer Terence , Venn Alison J.
Published: April 2008

The objective of this study was to determine whether change in physical activity was associated with maintaining a healthy weight from childhood to adulthood. This prospective cohort study examined 1,594 young Australian adults (48.9% female) aged 27–36 years who were first examined at age 9–15 years as part of a national health and fitness survey. BMI was calculated from measured height and weight, and physical activity was self‐reported at both time points; pedometers were also used at follow‐up. Change in physical activity was characterized by calculating the difference between baseline and follow‐upz‐scores. Change scores were categorized as decreasing (large, moderate), stable, or increasing (large, moderate). Healthy weight was defined in childhood as a BMI less than international overweight cutoff points, and in adulthood as BMI<25 kg/m2. Healthy weight maintainers were healthy weight at both time points. Compared with those who demonstrated large relative decreases in physical activity, females in all other groups were 25–37% more likely to be healthy weight maintainers, although associations differed according to the physical activity measure used at follow‐up and few reached statistical significance. Although younger males whose relative physical activity moderately or largely increased were 27–34% more likely to be healthy weight maintainers than those whose relative physical activity largely decreased, differences were not statistically significant. In conclusion, relatively increasing and stable physical activity from childhood to adulthood was only weakly associated with healthy weight maintenance. Examining personal, social, and environmental factors associated with healthy weight maintenance will be an important next step in understanding why some groups avoid becoming overweight.
11β‐Hydroxysteroid Dehydrogenase 2 Activity Is Elevated in Severe Obesity and Negatively Associated With Insulin Sensitivity
Authors: Müssig Karsten , Remer Thomas , Haupt Axel , Gallwitz Baptist , Fritsche Andreas , Häring Hans‐Ulrich , Maser‐Gluth Christiane
Published: April 2008

Alterations in glucocorticoid (GC) metabolism may contribute to the development of obesity and insulin resistance. We aimed to study the role of 11β‐hydroxysteroid dehydrogenase type 2 (11β‐HSD2) in human adiposity, paying special attention to the association between altered GC metabolism and insulin sensitivity. In 24‐h urine samples of 72 extremely obese (mean BMI 45.5 ± 1.1 kg/m2), but otherwise healthy patients urinary free cortisol (UFF), urinary free cortisone (UFE), tetrahydrocortisol (THF), 5α‐tetrahydrocortisol (5α‐THF), and tetrahydrocortisone (THE) were quantified by radioimmunoassay. The sum of the three major tetrahydrometabolites is an estimate for daily GC secretion, and the sum of UFF and UFE represents potentially bioactive‐free‐GCs. Thirty healthy lean subjects (BMI 22.3 ± 0.3 kg/m2) served as controls. In obese subjects, absolute daily GC secretion and the potentially bioactive‐free‐GCs were significantly (P < 0.005) higher than in lean controls (11.8 ± 0.7 vs. 8.0 ± 0.6 mg/d; and 171.8 ± 11.2 vs. 117.6 ± 9.2 μg/d, respectively). However, when these values were corrected for body surface area (BSA), significant differences were no longer detectable. While enzyme activity indices for 5α‐reductase and 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) were similar in lean and obese subjects, 11β‐HSD2 was markedly elevated in adiposity (3.7 ± 0.2 vs. 2.1 ± 0.1; P < 0.0001). This increase was accompanied by a significant reduction in UFF excretion corrected for BSA (16.5 ± 1.2 vs. 21.7 ± 2.0 μg/d/m2; P = 0.0222). Besides, 11β‐HSD2 activity was significantly correlated with insulin sensitivity (P = 0.0262). When body size is accounted for, both adrenal GC secretion and potentially bioactive‐free‐GCs are indistinguishable between lean and extremely obese subjects. However in obesity, the kidney appears to intensify its supply of the direct substrate cortisone for extrarenal 11β‐HSD1, which may fuel visceral adiposity and insulin resistance.
State Ranks of Incident Cancer Burden due to Overweight and Obesity in the United States, 2003
Authors: Chang Shine , Mâsse Louise C. , Moser Richard P. , Dodd Kevin W. , Arganaraz Facundo , Fuemmler Bernard F. , Jemal Ahmedin
Published: April 2008

Objective: Given links between obesity and cancer, we estimated incident cancer burden due to overweight and obesity at the state level in the United States.

Methods and Procedures: Using state rankings by per capita burden of incident cancer cases diagnosed in 2003 that were related to overweight and obesity, we examined the frequency with which states ranked in the highest and lowest quintiles of weight‐related burden for cancers of the postmenopausal breast, endometrium, kidney, colon, and prostate. In this study, data from the Behavioral Risk Factor Surveillance System (BRFSS), US Census, US Mortality Public Use Data Tapes, and National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program were used.

Results: Western states had the lowest weight‐related cancer burden for both sexes. Iowa, South Dakota, and West Virginia had the highest burden for all three types of male cancers. West Virginia is the only state that ranked in the quintile of highest weight‐related burden for all four cancers considered in women.

Discussion: For certain cancers, including endometrial, postmenopausal breast, and colon cancers, states with high burdens clustered in geographic regions, warranting further inquiry. Although state ranks for the total cancer burden and the prevalence of overweight and obesity correlated with state ranks for weight‐related incident cancer burden, they often served poorly as its proxy. Such a finding cautions against simply targeting states with high overweight and obesity or high total burdens of cancers for which overweight and obesity are risk factors, as this approach may not reach areas of unrecognized burden.
Evaluation of affinity constants of Cu, Cd, Ca and H for active soil surfaces for a solid phase-controlled soil ligand model
Authors: Rachou Julien , Sauvé Sébastien
Published: April 2008

Environmental context. The speciation of metals in soils is controlled by the equilibrium between the solid and aqueous phases and by several parameters such as pH and total metal concentrations. The integration of affinity constants between several cations and active soil surfaces of different soils in the chemical equilibrium modelling software MINEQL+ allows a good evaluation of the chemical speciation of the metals.

Abstract. A new approach, derived from the concept of the biotic ligand model, was used for the determination of the affinity constants of Ca, Cu, Cd and H to the active surfaces of different kinds of soils. This approach allowed us to obtain consistent data and to integrate these values in the chemical equilibrium modelling software MINEQL+ and eventually into a solid phase-controlled soil ligand model. This could then very easily be transformed into a terrestrial biotic ligand model by adding constants for biological components. We obtained the chemical speciation of the metals of interest by integrating the initial characteristics of the soil (pH; cation exchange capacity, CEC; total metal concentrations in soil extracts; ionic strength; and CO2 pressure). Comparison of the predicted and measured values of free Cu2+ is excellent using soil-specific affinity constants as well as average values. The average affinity constants between the active soil surfaces (S) and the target cations are log KCa–S = –0.84 (±0.01), log KCu–S = 5.3 (±0.1), log KCd–S = 4.4 (±0.2) and log KH–S = 4.1 (±0.2). External soils have been used to validate the conceptual model and the results show a very good correlation between the predicted and the measured free Cu (pCu) except for an acidic soil (pH < 5.2), highlighting the importance of integrating Al into the model.
IMMIGRANT ‘SPACE’ IN ITALY: WHEN AN EMIGRANT SENDING BECOMES AN IMMIGRANT RECEIVING SOCIETY
Authors: Hellman Judith Adler
Published: April 2008

This article examines the social and political responses to the new flow of immigrants to Italy from outside the European Union. First, the Italian experience is compared with the rest of Europe with respect to such questions as the characteristics of the immigrants themselves, and the response to them on the part of political parties, the church, the unions, and the state at local, regional and national levels. Next, broader comparisons are drawn between the Italian case and that of classic ‘societies of immigration’, particularly with regard to the structure of economic opportunity available to the extracomunitari in Italy.
Umberto Bossi: charisma, personality and leadership
Authors: Barraclough Richard
Published: April 2008

The Northern League is sometimes referred to as a ‘charismatic party’. The reason for this description is the presence of a highly visible—and audible—leader: Umberto Bossi. This article aims to demonstrate that Bossi is perceived as a charismatic leader largely thanks to a constructed personality and image which is designed to symbolize the League's identity. Since it is this image, along with Bossi's organizational skills and tactical abilities, rather than his ‘charisma’ which is the basis of his authority within the League, it is erroneous to regard the League as a true example of a charismatic party.
Nature, Craft, Domesticity, and the Culture of Consumption: the Feminine Face of Design in Italy, 1945–70
Authors: Sparke Penny
Published: April 2008

This article sets out to outline the way in which existing narratives dealing with the development of modern design in post-1945 Italy have ignored those aspects of the story which do not concur with a characterization of that phenomenon that relies on the concepts of rationality, mass production and the impact of new materials. By focusing on and elaborating a number of ‘other’ themes—namely those of nature, craft, domesticity and the culture of consumption—this study sets out to redress this imbalance and to introduce the possibility of a new reading of modern design in Italy which can be seen to be rooted in a set of cultural values which are more obviously feminine’ in nature.
Flightless-I regulates proinflammatory caspases by selectively modulating intracellular localization and caspase activity
Authors: Li Juying , Yin Helen L. , Yuan Junying
Published: April 2008

Caspase-1 and caspase-11 are proinflammatory caspases that regulate cytokine production and leukocyte migration during pathogen infection. In an attempt to identify new intracellular regulators of caspase-11, we found that Flightless-I, a member of the gelsolin superfamily of actin-remodeling proteins, interacts and regulates both caspase-11 and caspase-1. Flightless-I targets caspase-11 to the Triton X-100–insoluble cytoskeleton fraction and the cell leading edge. In addition, Flightless-I inhibits caspase-1 activation and caspase-1–mediated interleukine-1β (IL-1β) maturation. The physiological relevance of these findings is supported by the opposing effects of Flightless-I overexpression and knockdown on caspase-1 activity and IL-1β maturation. Our results suggest that Flightless-I may be a bona fide caspase-1 inhibitor that acts through a mechanism similar to that of cytokine response modifier A, a potent caspase-1 inhibitor from the cowpox virus. Our study provides a new mechanism controlling the localization and activation of proinflammatory caspases.
Spinophilin and the immune synapse
Authors: Seed Brian , Xavier Ramnik
Published: April 2008

Extensive alterations in cellular organization are known to accompany the responses of sensitized T cells to target cells presenting an antigen of interest. Now, equally if not more dramatic changes are found to take place in cells presenting an antigen. With the help of a spinophilin-GFP fusion protein, Bloom et al. (Bloom, O., J.J. Unternaehrer, A. Jiang, J.-S. Shin, L. Delamarre, P. Allen, and I. Mellman. 2008. J. Cell Biol. 181:203–211) have captured a remarkable polarization of the cellular architecture of dendritic cells presenting an antigen to T cells.
A Role for DPPX Modulating External TEA Sensitivity of Kv4 Channels
Authors: Colinas Olaia , Pérez-Carretero Francisco D. , López-López José R. , Pérez-García M. Teresa
Published: April 2008

Shal-type (Kv4) channels are expressed in a large variety of tissues, where they contribute to transient voltage-dependent K+ currents. Kv4 are the molecular correlate of the A-type current of neurons (ISA), the fast component of ITO current in the heart, and also of the oxygen-sensitive K+ current (KO2) in rabbit carotid body (CB) chemoreceptor cells. The enormous degree of variability in the physiological properties of Kv4-mediated currents can be attributable to the complexity of their regulation together with the large number of ancillary subunits and scaffolding proteins that associate with Kv4 proteins to modify their trafficking and their kinetic properties. Among those, KChIPs and DPPX proteins have been demonstrated to be integral components of ISA and ITO currents, as their coexpression with Kv4 subunits recapitulates the kinetics of native currents. Here, we explore the presence and functional contribution of DPPX to KO2 currents in rabbit CB chemoreceptor cells by using DPPX functional knockdown with siRNA. Additionally, we investigate if the presence of DPPX endows Kv4 channels with new pharmacological properties, as we have observed anomalous tetraethylammonium (TEA) sensitivity in the native KO2 currents. DPPX association with Kv4 channels induced an increased TEA sensitivity both in heterologous expression systems and in CB chemoreceptor cells. Moreover, TEA application to Kv4-DPPX heteromultimers leads to marked kinetic effects that could be explained by an augmented closed-state inactivation. Our data suggest that DPPX proteins are integral components of KO2 currents, and that their association with Kv4 subunits modulate the pharmacological profile of the heteromultimers.
Hemodynamic Changes Associated with Spinal Anesthesia for Cesarean Delivery in Severe Preeclampsia
Authors: Dyer Robert A. , Piercy Jenna L. , Reed Anthony R. , Lombard Carl J. , Schoeman Leann K. , James Michael F.
Published: April 2008

Background

Hemodynamic responses to spinal anesthesia (SA) for cesarean delivery in patients with severe preeclampsia are poorly understood. This study used a beat-by-beat monitor of cardiac output (CO) to characterize the response to SA. The hypothesis was that CO would decrease from baseline values by less than 20%.

Methods

Fifteen patients with severe preeclampsia consented to an observational study. The monitor employed used pulse wave form analysis to estimate nominal stroke volume. Calibration was by lithium dilution. CO and systemic vascular resistance were derived from the measured stroke volume, heart rate, and mean arterial pressure. In addition, the hemodynamic effects of phenylephrine, the response to delivery and oxytocin, and hemodynamics during recovery from SA were recorded. Hemodynamic values were averaged for defined time intervals before, during, and after SA.

Results

Cardiac output remained stable from induction of SA until the time of request for analgesia. Mean arterial pressure and systemic vascular resistance decreased significantly from the time of adoption of the supine position until the end of surgery. After oxytocin administration, systemic vascular resistance decreased and heart rate and CO increased. Phenylephrine, 50 mug, increased mean arterial pressure to above target values and did not significantly change CO. At the time of recovery from SA, there were no clinically relevant changes from baseline hemodynamic values.

Conclusions

Spinal anesthesia in severe preeclampsia was associated with clinically insignificant changes in CO. Phenylephrine restored mean arterial pressure but did not increase maternal CO. Oxytocin caused transient marked hypotension, tachycardia, and increases in CO.
Utility of the Photoplethysmogram in Circulatory Monitoring
Authors: Reisner Andrew , Shaltis Phillip A. , McCombie Devin , Asada H Harry , Warner David S. , Warner Mark A.
Published: April 2008

The photoplethysmogram is a noninvasive circulatory signal related to the pulsatile volume of blood in tissue and is displayed by many pulse oximeters and bedside monitors, along with the computed arterial oxygen saturation. The photoplethysmogram is similar in appearance to an arterial blood pressure waveform. Because the former is noninvasive and nearly ubiquitous in hospitals whereas the latter requires invasive measurement, the extraction of circulatory information from the photoplethysmogram has been a popular subject of contemporary research. The photoplethysmogram is a function of the underlying circulation, but the relation is complicated by optical, biomechanical, and physiologic covariates that affect the appearance of the photoplethysmogram. Overall, the photoplethysmogram provides a wealth of circulatory information, but its complex etiology may be a limitation in some novel applications.
Effects of Anemia and Hypotension on Porcine Optic Nerve Blood Flow and Oxygen Delivery
Authors: Lee Lorri A. , Deem Steven , Glenny Robb W. , Townsend Ian , Moulding Jennifer , An Dowon , Treggiari Miriam M. , Lam Arthur
Published: April 2008

Background

Perioperative ischemic optic neuropathy occurs after major surgical procedures, which are often associated with hypotension, anemia, or venous congestion. However, the effects of these conditions on optic nerve (ON) blood flow are unknown and cannot be studied adequately in humans.

Methods

Farm-raised pigs were anesthetized with isoflurane, kept normocapnic and normothermic, and subjected to conditions of euvolemic or hypovolemic hypotension (mean arterial pressure 50-55 mm Hg), anemia (hematocrit 17%), venous congestion, and combinations thereof. Control animals were kept euvolemic and normotensive for the entire experiment. Fluorescent microspheres were used to measure cerebral blood flow (CBF) and ON blood flow at baseline and after experimental conditions, and to calculate oxygen delivery (DO2).

Results

No significant changes in CBF or ON blood flow or DO2 occurred with euvolemic hypotension (n = 5), compared with controls (n = 12). Hypovolemic hypotension (n = 4) resulted in stable CBF and cerebral DO2, but significant reductions in ON DO2 (P = 0.032). The significant increase in CBF associated with anemia (n = 6) resulted in stable cerebral DO2. In contrast, ON blood flow did not significantly change with anemia, with (n = 5) or without (n = 6) euvolemic hypotension, resulting in significant reductions in ON DO2 (P < 0.01).

Conclusion

Compensatory mechanisms for porcine CBF maintain stable DO2 under specified conditions of hypotension or anemia, whereas ON compensatory mechanisms were unable to maintain blood flow and to preserve DO2. The authors conclude that the porcine ON is more susceptible to physiologic perturbations than the brain.
Restriction of human herpesvirus 6B replication by p53
Authors: Øster Bodil , Kofod-Olsen Emil , Bundgaard Bettina , Höllsberg Per
Published: April 2008

Human herpesvirus 6B (HHV-6B) induces significant accumulation of p53 in both the nucleus and cytoplasm during infection. Activation of p53 by DNA damage is known to induce either growth arrest or apoptosis; nevertheless, HHV-6B-infected cells are arrested in their cell cycle independently of p53, and only a minor fraction of the infected cells undergoes apoptosis. Using pifithrin-α, a p53 inhibitor, and p53-null cells, this study showed that infected epithelial cells accumulated viral transcripts and proteins to a significantly higher degree in the absence of active p53. Moreover, HHV-6B-induced cytopathic effects were greatly enhanced in the absence of p53. This suggests that, in epithelial cells, some of the functions of p53 leading to cell-cycle arrest and apoptosis are restrained by HHV-6B infection, whereas other cellular defences, causing inhibition of virus transcription, are partially retained.
DNA vaccination in combination or not with lamivudine treatment breaks humoral immune tolerance and enhances cccDNA clearance in the duck model of chronic hepatitis B virus infection
Authors: Thermet Alexandre , Buronfosse Thierry , Werle-Lapostolle Bettina , Chevallier Michele , Pradat Pierre , Trepo Christian , Zoulim Fabien , Cova Lucyna
Published: April 2008

This study used a duck hepatitis B virus (DHBV) model to evaluate whether a novel DNA vaccination protocol alone or associated with antiviral (lamivudine) treatment was able to clear the intrahepatic covalently closed, circular viral DNA (cccDNA) pool responsible for persistence of infection. DHBV carriers received DNA vaccine (on weeks 6, 10, 13, 14, 28 and 35) targeting the large envelope and/or core proteins alone or combined with lamivudine treatment (on weeks 1–8) or lamivudine monotherapy. After 10 months of follow-up, a dramatic decrease in viraemia and liver DHBV cccDNA (below 0.08 cccDNA copies per cell) was observed in 9/30 ducks (30 %) receiving DNA mono- or combination therapy, compared with 0/12 (0 %) from lamivudine monotherapy or the control groups, suggesting a significant antiviral effect of DNA immunization. However, association with the drug did not significantly improve DHBV DNA vaccine efficacy (33 % cccDNA clearance for the combination vs 27 % for DNA monotherapy), probably due to the low antiviral potency of lamivudine in the duck model. Seroconversion to anti-preS was observed in 6/9 (67 %) ducks showing cccDNA clearance, compared with 1/28 (3.6 %) without clearance, suggesting a significant correlation (P<0.001) between humoral response restoration and cccDNA elimination. Importantly, an early (weeks 10–12) drop in viraemia was observed in seroconverted animals, and virus replication did not rebound following the cessation of immunotherapy, indicating a sustained effect. This study provides the first evidence that therapeutic DNA vaccination is able to enhance hepadnaviral cccDNA clearance, which is tightly associated with a break in humoral immune tolerance. These results also highlight the importance of antiviral drug potency and an effective DNA immunization protocol for the design of therapeutic vaccines against chronic hepatitis B.
Identification of amino acids of the beet necrotic yellow vein virus p25 protein required for induction of the resistance response in leaves of Beta vulgaris plants
Authors: Chiba Soutaro , Miyanishi Masaki , Andika Ida Bagus , Kondo Hideki , Tamada Tetsuo
Published: April 2008

The RNA3-encoded p25 protein of beet necrotic yellow vein virus (BNYVV) is responsible for the production of rhizomania symptoms of sugar beet roots (Beta vulgaris subsp. vulgaris). Here, it was found that the presence of the p25 protein is also associated with the resistance response in rub-inoculated leaves of sugar beet and wild beet (Beta vulgaris subsp. maritima) plants. The resistance phenotype displayed a range of symptoms from no visible lesions to necrotic or greyish lesions at the inoculation site, and only very low levels of virus and viral RNA accumulated. The susceptible phenotype showed large, bright yellow lesions and developed high levels of virus accumulation. In roots after Polymyxa betae vector inoculation, however, no drastic differences in virus and viral RNA accumulation levels were found between plants with susceptible and resistant phenotypes, except at an early stage of infection. There was a genotype-specific interaction between BNYVV strains and two selected wild beet lines (MR1 and MR2) and sugar beet cultivars. Sequence analysis of natural BNYVV isolates and site-directed mutagenesis of the p25 protein revealed that 3 aa residues at positions 68, 70 and 179 are important in determining the resistance phenotype, and that host-genotype specificity is controlled by single amino acid changes at position 68. The mechanism of the occurrence of resistance-breaking BNYVV strains is discussed.
Genetic-linkage mapping of complex hereditary disorders to a whole-genome molecular-interaction network
Authors: Iossifov Ivan , Zheng Tian , Baron Miron , Gilliam T. Conrad , Rzhetsky Andrey
Published: April 2008

Common hereditary neurodevelopmental disorders such as autism, bipolar disorder, and schizophrenia are most likely both genetically multifactorial and heterogeneous. Because of these characteristics traditional methods for genetic analysis fail when applied to such diseases. To address the problem we propose a novel probabilistic framework that combines the standard genetic linkage formalism with whole-genome molecular-interaction data to predict pathways or networks of interacting genes that contribute to common heritable disorders. We apply the model to three large genotype–phenotype data sets, identify a small number of significant candidate genes for autism (24), bipolar disorder (21), and schizophrenia (25), and predict a number of gene targets likely to be shared among the disorders.
Case of anaphylaxis caused by ingestion of royal jelly
Authors: KATAYAMA Mirei , AOKI Mikako , KAWANA Seiji
Published: April 2008

Anaphylaxis is a severe form of allergic disease. Royal jelly is widely consumed in Japan, but a few cases of anaphylaxis caused by royal jelly have been reported. We encountered a 26‐year‐old Japanese woman who developed anaphylaxis after drinking a beverage of crude royal jelly including honey. She had a history of bronchial asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis and food allergy (abalone). Prick tests were performed with the beverage of crude royal jelly including honey and with two other beverages including honey. Only the crude royal jelly beverage showed a positive reaction. An oral challenge test with the crude royal jelly beverage was not performed, but a similar test with a beverage including honey caused no symptoms. A positive response to the beverage of crude royal jelly was not observed in normal volunteers. A positive diagnosis of anaphylaxis due to royal jelly was made based on the positive prick test, systemic clinical symptoms and the negative prick tests in healthy volunteers. Moreover, the patient had no symptoms when taking lemon and orange, which were present as essences in the crude royal jelly beverage, and also had no response to honey after anaphylaxis. Increased consumption of royal jelly in health food supplements may increase the incidence of royal jelly‐related allergic reactions. Therefore, royal jelly should be considered as a causative allergen in food‐induced anaphylaxis.
Destiny matters: distal developmental influences on adult alcohol use and abuse
Authors: Schulenberg John E. , Maggs Jennifer L.
Published: April 2008

A foundational assumption in the fields of addiction and developmental psychopathology is that child and adolescent experiences set the stage for adult functioning and adjustment. However, the empirical literature documenting life‐span linkages with adult alcohol (and other drug) use and abuse is sparse. This gap is due to a slow adoption of life‐span developmental conceptualizations and the lack of long‐term prospective longitudinal studies. This supplemental issue provides evidence for such linkages from six long‐term longitudinal studies, which together follow individuals from birth through to the late 40s. The data sets include national and regional samples from Britain, Finland and the United States. In this introductory paper, we consider conceptual issues concerning linkages across the life‐span culminating in adult alcohol use and disorders, and provide a summary of the purposes and common themes.
Season of grazing and stocking rate interactively affect fuel loads in Baikiaea plurijuga Harms woodland in northwestern Zimbabwe
Authors: Gambiza J. , Campbell B. M. , Moe S. R. , Mapaure I.
Published: April 2008

Wildfire is a major disturbance in Baikiaea plurijuga Harms woodland savannas. We tested the hypothesis that the timing and intensity of herbivory influence fuel loads. We used three stocking rates namely light (three cows and four goats ha−1), medium (six cows and eight goats ha−1) and heavy (eleven cows and sixteen goats ha−1) and three times of grazing namely early‐, middle‐ and late‐growing seasons. Season of grazing and stocking rate influenced herbaceous phytomass. Phytomass was generally the highest (53.5 g DM m−2) in paddocks grazed during the early growing season and the lowest (27.8 g DM m−2) in those grazed during the late growing season. Phytomass was also generally the highest (40.4 g DM m−2) in lightly stocked paddocks and the lowest (32.7 g DM m−2) in heavily stocked ones. Litter mass was the lowest (160.8 g DM m−2) in paddocks grazed during the early season whereas there were no differences in ungrazed paddocks and those grazed during either mid‐ or late growing seasons (205.4 g DM m−2). There was a negative relationship between litter mass and stocking rate. Baikiaea Benth. woodlands should be grazed during either the mid‐ or late‐growing season at stocking rates greater than 0.1 LU ha−1 to reduce grass fuel loads.