bluuebunny/crossref_metadata_2025 huggingface dataset:
Deuteration of Water Enables Self‐Organization of Phospholipid‐Based Reverse Micelles
Authors: Milhaud Jeannine , Bouchemal Nadia , Rog Tomasz , Hantz Edith
Published: February 2010

Phospholipid‐based reverse micelles are composed of branched cylinders. Their branching points are known to attract themselves and to slide along branches. The rate of this sliding is governed by the lifetime of H(D)‐bonded water bridges between phospholipid molecules. This lifetime is increased when the water is deuterated. On condition that the water contains at least 40 D atoms %, water/dipalmitoylphosphatidylcholine (DPPC)/deuterated pyridine reverse micelles with the composition 1.1:1:250 (v/v) have been shown to self‐organize into a liquid crystal in the 310–316 K temperature range. The mechanism of this self‐organization is unraveled by following the FTIR and 1H NMR spectra of more concentrated micelles upon heating. During the preparation of micelles, pyridine‐(D+)H+ ions are formed. They give rise to hydron transfers, under the influence of the DPPC electric charges, evidenced by two broad FTIR absorptions above (BB1) and below (BB2) the ν(CO) stretch. These hydron transfers occur along strong (D+)H+ bonds of pyridinium ions with pyridine (BB1) and DPPC CO groups (BB2). The proton transfers at the interface of micelles, relayed in the continuous pyridine medium, create a tenuous link between separated micelles, thus facilitating their organization. Upon heating, DPPC heads shrink and DPPC chains expand to make wedge‐shaped DPPC molecules. The micelles then change in shape: cylinders constrict and enclosed water drifts towards branching points, which swell. Branching points of neighboring micelles come into contact. Due to the deuteration of water these contacts are prolonged and H bonds are formed between DPPC molecules located in each branching point. Upon storage at 39 °C, these branching points fuse. The lateral diffusion of DPPC molecules becomes free, as evidenced by a narrowing of all 1H NMR resonances. Upon further heating, reorganization into a liquid crystal occurs.
Plasma homocysteine levels are associated with ulceration of the foot in patients with type 2 diabetes mellitus
Authors: González R. , Pedro T. , Real Jose T. , Martínez‐Hervás S. , Abellán M. R. , Lorente R. , Priego A. , Catalá M. , Chaves F. J. , Ascaso J. F. , Carmena R.
Published: February 2010

Background

To examine the association of biochemical markers of risk (plasma Hcy, microalbuminuria, lipoprotein (a)(Lp(a)) and diabetic dyslipidaemia) with the prevalence of diabetic foot ulceration in type 2 diabetic patients.

Methods

Case/control study conducted in 198 type 2 diabetic patients. 89 patients have foot ulcers and 109 have no foot ulcers (control group), in order to establish ORs for diabetic foot ulceration. In all subjects plasma Hcy, Lp(a), total cholesterol, triglycerides, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, apolipoprotein B, HbA1c and microalbuminuria were measured using standard procedures.

Results

Plasma Hcy, microalbuminuria, HbA1c and apolipoprotein B levels were significantly higher in patients with foot ulceration compared with the control group. Plasma lipids, Lp(a), vitamin B12 and folic acid values were similar in both groups. In the logistic regression model, plasma Hcy (OR 1.09; 95% CI 1.04–1.69), microalbuminuria (OR 1,01; 95% CI 1.01–1.17) and HbA1c levels (OR 1.33; 95% CI 1.04–1.69) were independent risk factors for the presence of diabetic foot ulceration.

Conclusions

In our study, for each µmol increase in plasma Hcy levels there was a 10% increase in the risk of diabetic foot ulceration. In addition, plasma homocyteine, HbA1c and microalbuminuria accounted for 50% prevalence risk of diabetic foot ulceration. Further prospective studies should be conducted to confirm the association of plasma Hcy levels with the risk of foot ulceration. Copyright © 2010 John Wiley & Sons, Ltd.
Effects of dyslexia on postural control in adults
Authors: Patel M. , Magnusson M. , Lush D. , Gomez S. , Fransson P. A.
Published: February 2010

Dyslexia has been shown to affect postural control. The aim of the present study was to investigate the difference in postural stability measured as torque variance in an adult dyslexic group (n=14, determined using the Adult Dyslexia Checklist (ADCL) and nonsense word repetition test) and an adult non‐dyslexic group (n=39) on a firm surface and on a foam block and with eyes open and eyes closed. Another aim was to investigate the correlation between ADCL scores and postural stability.

Findings showed that ADCL scores correlated with torque variance in the anteroposterior direction on foam with eyes closed (p=0.001) and in the lateral direction on the foam surface with eyes closed (p=0.040) and open (p=0.010). General Linear Model analysis showed that high dyslexia scores were associated with increased torque variance (p<0.001). However, we found no significant difference between dyslexics and non‐dyslexics, though there were indications of larger torque variance in the dyslexics.

The findings suggest that adults with high dyslexic ADCL scores may experience sub‐clinical balance deficits. Hence, assessing motor ability and postural control in those with high ADCL scores is motivated. Copyright © 2010 John Wiley & Sons, Ltd.
Thymic stromal lymphopoietin induces early human B‐cell proliferation and differentiation
Authors: Scheeren Ferenc A. , van Lent Anja U. , Nagasawa Maho , Weijer Kees , Spits Hergen , Legrand Nicolas , Blom Bianca
Published: February 2010

Thymic stromal lymphopoietin (TSLP) is a cytokine that binds the IL‐7‐receptor‐α chain and a unique TSLP receptor (TSLPR) chain. The role of TSLP in human B‐cell development has not been elucidated. We show that TSLPR transcripts are expressed most prominently in CD34+ cells from fetal liver and BM. In general, cell surface expression of TSLPR was low, except on a subset of multilineage‐commited progenitor cells. TSLP induced the tyrosine‐phosphorylation of STAT5 and the proliferation of multilineage‐commited progenitor cells, pro‐B cells and pre‐B cells. Compared with IL‐7, the levels of proliferation after stimulation of the B‐cell progenitors with TSLP were lower. Expression of the BCR on the cell surface of fetal cells was inversely correlated to TSLP or IL‐7 responsiveness. Pre‐B cells from fetal BM, but not fetal liver, were refractory to TSLP or IL‐7 stimulation. When employing an in vitro B‐cell differentiation culture system starting from CD34+CD38− multipotent HSC, IL‐7 induced a short wave of precursor cell expansion but did not result in long‐term survival of mature B cells. TSLP was capable of increasing the proportion and the absolute numbers of more mature human B cells. Overall, we provide evidence that TSLP supports human B‐cell differentiation from fetal hematopoietic progenitors.
The cyclin‐dependent kinase inhibitor R‐roscovitine down‐regulates Mcl‐1 to override pro‐inflammatory signalling and drive neutrophil apoptosis
Authors: Leitch Andrew E. , Riley Nicola A. , A. Sheldrake Tara , Festa Michela , Fox Sarah , Duffin Rodger , Haslett Christopher , Rossi Adriano G.
Published: February 2010

Successful resolution of inflammation requires inflammatory cells such as neutrophils to undergo apoptosis prior to non‐inflammatory phagocytosis by professional phagocytes. Recently, cyclin‐dependent kinase (CDK) inhibitors (e.g. R‐roscovitine) have been shown to induce neutrophil apoptosis and enhance the resolution of inflammation. Interestingly, NF‐κB and MAPK pathways and key endogenous survival proteins (typified by Mcl‐1) are involved in the regulation of neutrophil apoptosis and, in cancer‐cell lines, have been implicated as possible targets of CDK inhibitors. Here, we demonstrate that R‐roscovitine over‐rides TNF‐α and LPS‐induced survival (determined by morphological examination and binding of fluorescently labelled annexin‐V) of isolated peripheral blood neutrophils. This effect did not appear to be mediated via effects on early markers of neutrophil activation (e.g. surface marker expression, shape change, aggregation and superoxide anion generation), by direct inhibition of NF‐κB activation (assessed by cytoplasmic IκBα proteolysis and NF‐κB p65 subunit translocation) and ERK activation (determined by specific ERK phosphorylation) but due to down‐regulation (at protein and mRNA level) of the survival protein Mcl‐1 but not the pro‐apoptotic bcl‐2 homologue Bim. These findings suggest that key endogenous survival proteins may be the targets of CDK inhibitors and consequently may be of critical importance in the resolution of inflammation.
Co‐expression of TNFR2 and CD25 identifies more of the functional CD4+FOXP3+ regulatory T cells in human peripheral blood
Authors: Chen Xin , Subleski Jeffrey J. , Hamano Ryoko , Howard O. M. Zack , Wiltrout Robert H. , Oppenheim Joost J.
Published: February 2010

Previously, we found that co‐expression of CD25 and TNFR2 identified the most suppressive subset of mouse Treg. In this study, we report that human peripheral blood (PB) FOXP3+ cells present in CD25high, CD25low and even CD25– subsets of CD4+ cells expressed high levels of TNFR2. Consequently, TNFR2‐expressing CD4+CD25+ Treg included all of the FOXP3+ cells present in the CD4+CD25high subset as well as a substantial proportion of the FOXP3+ cells present in the CD4+CD25low subset. Flow cytometric analysis of PB identified five‐fold more Treg, determined by FOXP3 expression, in the CD4+CD25+TNFR2+ subset than in the CD4+CD25high subset. In addition, similar levels of FOXP3+ cells were identified in both the CD4+CD25+TNFR2+ and CD4+CD25+CD127low/− subsets. Furthermore, the CD4+CD25+TNFR2+ subset expressed high levels of CTLA‐4, CD45RO, CCR4 and low levels of CD45RA and CD127, a phenotype characteristic of Treg. Upon TCR stimulation, human PB CD4+CD25+TNFR2+ cells were anergic and markedly inhibited the proliferation and cytokine production of co‐cultured T‐responder cells. In contrast, CD4+CD25+TNFR2– and CD4+CD25–TNFR2+ T cells did not show inhibitory activity. As some non‐Treg express TNFR2, the combination of CD25 and TNFR2 must be used to identify a larger population of human Treg, a population that may prove to be of diagnostic and therapeutic benefit in cancer and autoimmune diseases.
Access to a Novel Class of Tetracyclic 1,4‐Benzodiazepin‐5‐ones Starting from α‐Amino Acids by Pd‐Catalyzed Amination/1,3‐Dipolar Cycloaddition as the Key Steps
Authors: Basolo Luca , Beccalli Egle M. , Borsini Elena , Broggini Gianluigi , Khansaa Maisaa , Rigamonti Micol
Published: February 2010

A convenient procedure for the preparation of the novel class of tetracyclic imidazo[2,1‐c]pyrazolo[1,5‐a][1,4]benzodiazepine‐5,8‐diones is reported. The protocol uses cheap andeasily accessible α‐amino acids as chiral‐pool starting materials and leads to products in an enantiopure form. An intramolecular palladium‐catalyzed amination process to form the imidazole nucleus and an intramolecular 1,3‐dipolar cycloaddition reaction to simultaneously achieve the pyrazole and 1,4‐diazepine rings are the key steps.
Oligoaryl Cruciform Structures as Model Compounds for Coordination‐Induced Single‐Molecule Switches (Eur. J. Org. Chem. 5/2010)
Authors: Grunder Sergio , Huber Roman , Wu Songmei , Schönenberger Christian , Calame Michel , Mayor Marcel
Published: February 2010

The cover picture shows the fertile combination of synthetic chemistry and experimental physics, both permanently making central contributions to hot scientific topics in spite of being classical scientific disciplines with long‐standing traditions. The displayed scientist struggles with the synthesis of cruciform structures (displayed on the black board) for single‐molecule‐transport investigations in a mechanically controlled break junction setup (sketched in the inset at the upper right corner). More information on the design and synthesis of the cruciform structures, such as their immobilization experiments, is found in the article by M. Calame, M. Mayor et al. on p. 833 ff. Serafin Pazdera is greatly acknowledged for the cover artwork.
The influence of dunes on mixing in a migrating salt‐wedge: Fraser River estuary, Canada
Authors: Kostaschuk Ray , Best Jim , Villard Paul V.
Published: February 2010

Dune bedforms and salt‐wedge intrusions are common features in many estuaries with sand beds, and yet little is known about the interactions between the two. Flow visualization with an echosounder and velocity measurements with an acoustic Doppler current profiler over areas of flat‐bed and sand dunes in the highly‐stratified Fraser River estuary, Canada, were used to examine the effect of dunes on interfacial mixing. As the salt‐wedge migrates upstream over the flat‐bed, mixing is restricted to the lower portion of the water column. However, as the salt‐wedge migrates into the dune field from the flat bed, there is a dramatic change in the flow, and large internal in‐phase waves develop over each of the larger dunes, with water from the salt‐wedge reaching the surface of the estuary. The friction Richardson number shows that bed friction is more important in interfacial mixing over the dunes than over the flat‐bed, and a plot of internal Froude Number versus obstacle (dune) height shows that the salt‐wedge flow over the dunes is mainly supercritical. Such bedforms can be expected to cause similar effects in interfacial mixing in other estuaries and sediment‐laden density currents, and may thus be influential in fluid mixing and sediment transport. Copyright © 2010 John Wiley & Sons, Ltd.
Coupling mechanisms in double sandbar systems. Part 1: patterns and physical explanation
Authors: Castelle Bruno , Ruessink B. G. , Bonneton Philippe , Marieu Vincent , Bruneau Nicolas , Price Timothy D.
Published: February 2010

Crescentic sandbars and rip channels along wave‐dominated sandy beaches are relevant to understand localized beach and dune erosion during storms. In recent years, a paradigm shift from hydrodynamic template models to self‐organization mechanisms occurred to explain the formation of these rhythmic features. In double sandbar systems, both the inner‐ and outer‐bar rip channels and crescentic planshapes are now believed to be free instabilities of the nearshore system arising through self‐organization mechanisms alone. However, the occasional occurrence of one or two inner‐bar rip channels within one outer‐bar crescent suggests a forced, morphologically coupled origin. Here we use a nonlinear morphodynamic model to show that alongshore variability in outer‐bar depth, and the relative importance of wave breaking versus wave focussing by refraction across the outer bar, is crucial to the inner‐bar rip channel development. The coupling patterns simulated by our model are similar to those observed in the field. Morphological coupling requires a template in the morphology (outer‐bar geometry) which, through the positive feedback between flow, sediment transport and the evolving morphology (that is, self‐organization) enforces the development of coupling patterns. We therefore introduce a novel mechanism that blurs the distinction between self‐organization and template mechanisms. This mechanism may also be extended to explain the dynamics of other nearshore patterns, such as beach cusps. The impact of this novel mechanism on the alongshore variability of inner‐bar rip channels is investigated in the companion paper. Copyright © 2010 John Wiley and Sons, Ltd.
Characterization of rainfall generated by dripper‐type rainfall simulator using piezoelectric transducers and its impact on splash soil erosion
Authors: Abd Elbasit Mohamed A. M. , Yasuda Hiroshi , Salmi Atte , Anyoji Hisao
Published: February 2010

Rainfall erosivity represents the primary driver for particle detachment in splash soil erosion. Several raindrop erosivity indices have been developed in order to quantify the potential of rainfall to cause soil erosion. Different types of rainfall simulators have been used to relate rainfall characteristics to soil detachment. However, rainfall produced by different rainfall simulators has different characteristics, specifically different relationships between rainfall intensity and rainfall erosivity. For this reason, the effect of rainfall characteristics produced by a dripper‐type rainfall simulator on splash soil erosion (Ds) has been investigated. The simulated rainfall kinetic energy (KE) and drop size distribution (DSD) were measured using piezoelectric transducers, modified from the Vaisala RAINCAP® rain sensor. The soil splash was evaluated under various simulated rainfall intensities ranging from 10 to 100 mm h−1 using the splash‐cup method. The simulated rainfall intensity (I) and kinetic energy relationship (I–KE) was found to be different from natural rainfall. The simulated rainfall intensity and splash soil erosion relationship (I–Ds) also followed this same trend. The I–KE relationship was found to follow the natural rainfall trend until the rainfall intensity reached 30 mm h−1 and above this limit the KE started to decrease. This emphasizes the importance of the I–KE relationship in determining the I‐Ds relationship, which can differ from one rainfall simulator to another. Ds was found to be highly correlated with KE (r = 0·85, P < 0·001), when data produced by the rainfall intensity ranged from 10 to 100 mm h−1. However, when the threshold rainfall intensity (30 mm h−1) was considered, the correlation coefficient further improved (r = 0·89, P = 0·001). Accordingly, to improve the soil splash estimation of simulated rainfall under various rainfall intensities the I–KE characterization relationship for rainfall simulators has to be taken into account. Copyright © 2010 John Wiley & Sons, Ltd.
Coupling mechanisms in double sandbar systems. Part 2: impact on alongshore variability of inner‐bar rip channels
Authors: Castelle Bruno , Ruessink B. G. , Bonneton Philippe , Marieu Vincent , Bruneau Nicolas , Price Timothy D.
Published: February 2010

Double sandbar systems are common morphological features along sandy, wave‐dominated, micro‐ to meso‐tidal coastlines. In the companion paper, we demonstrated how various alongshore inner‐bar rip‐channel patterns can develop through morphological coupling to an alongshore‐variable outer bar. The simulated coupling patterns are, however, scarcely observed in the field. Instead, inner‐bar rip channels more often possess remarkably smaller and more variable alongshore length scales, suggesting that coupling mechanisms do not play a substantial role in the overall double‐sandbar dynamics. Here we use a numerical model to show that the relative importance of self‐organization and morphological coupling changes in favour of the latter with an increase in waterdepth variability along the outer‐bar crest. Furthermore, we find that the typical alongshore variability in inner‐bar rip‐channel scale is indicative of a mixture of self‐organization and morphological coupling rather than self‐organization alone. Morphological coupling may thus be more important to understanding and predicting the evolution of inner‐bar rip channels than previously envisaged. Copyright © 2010 John Wiley and Sons, Ltd.
High resolution, basin extent observations and implications for understanding river form and process
Authors: Fonstad Mark A. , Marcus W. Andrew
Published: February 2010

Fifty years of fluvial studies have posited a variety of conceptual frameworks for characterizing river forms and processes throughout entire basins, including hydraulic geometry, the river continuum concept, self‐organized criticality, and sediment links. This article uses basin‐extent, high resolution observations of fluvial forms in the Nueces River basin, Texas, and Yellowstone National Park to evaluate the ability of these frameworks to characterize system behavior across a multitude of scales. The Nueces data were collected with remote sensing methods and the Yellowstone data were collected through extensive field surveys. The data resolution, spatial extent, and quality of these data sets allow direct comparison between the two areas.

The ‘hyperscale’ comparison supports using of each these frameworks at specific scales, but also indicates an irreducible amount of variation in both datasets across many different scales that is not captured by the conceptual frameworks. Moreover, the scales and locations where one framework, such as hydraulic geometry, works well are often not the same scales and locations where another framework, such as the river continuum concept, works well.

Because the conceptual frameworks appear to operate at scales and locations distinct from one another, the measurement approaches necessary to observe them must also be at different scales and locations. For example, ‘seeing’ self‐organized criticality in a river system is difficult without an extensive survey through space, whereas the recognition of sediment links requires quite intense sampling in specific river regions. We suggest that these separations between measurement scales represent an incommensurability issue in river studies, making it very difficult to both communicate among and test between two or more competing theories. Making simultaneous hyperscale observations of the river is one approach to minimizing the theory‐ladeness of observation, as deviations from different predictions can be plotted at every scale. Copyright © 2010 John Wiley & Sons, Ltd.
Uplink scheduling in LTE systems using distributed base stations
Authors: Yaacoub Elias , Dawy Zaher
Published: February 2010

Uplink scheduling in Long‐Term Evolution (LTE) systems with distributed base stations (DBSs) is considered. In the proposed model, users are connected to remote radio heads (RRHs) deployed throughout the cell and connected to a central base station. Centralised and distributed scheduling with a DBS are compared to centralised scheduling with a central base station. Monte Carlo simulation results show that LTE systems with DBSs achieve better throughput than systems with conventional base stations while allowing edge users better chances of accessing the resources. Copyright © 2010 John Wiley & Sons, Ltd.
Crossing the Language Barrier
Authors: Harnisch Rüdiger
Published: February 2010

The Iron Curtain not only bisected the inhabitants' homeland – in the Thuringian‐Bavarian region, the political divide also caused a surprising shift in their dialects.
In the Virtual Realm of the Myrmecologists
Authors: Pfeiffer Martin
Published: February 2010

The amazing diversity of ant fauna in Southeast Asia is showcased in a new scientific internet portal. High‐resolution automontage photographs show even the smallest of anatomical details – a valuable aid for ant researchers all over the world
“Directing Attention to the Essentials”
Authors: Unterstell Rembert
Published: February 2010

Between information and entertainment: Bernhard Fink presents his video diary “Love á la Darwin” on DFG Science TV – benefitting not only science communication but his research as well
Down-Regulation of Tyrosine Aminotransferase at A Frequently Deleted Region 16Q22 Contributes to the Pathogenesis of Hepatocellular Carcinoma
Authors: Fu Li , Dong Sui-Sui , Xie Yi-Wu , Tai Lai-Shan , Chen Leilei , Kong Kar Lok , Man Kwan , Xie Dan , Li Yan , Cheng Yingduan , Tao Qian , Guan Xin-Yuan
Published: February 2010

Loss of 16q is one of the most frequent alterations in many malignancies including hepatocellular carcinomas (HCC), suggesting the existence of a tumor suppressor gene (TSG) within the frequently deleted region. In this report we describe the identification and characterization of one candidate TSG, tyrosine aminotransferase gene (

TAT

), at 16q22.1. Loss of one

TAT

allele was detected in 27/50 (54%) of primary HCCs by quantitative real-time polymerase chain reaction. In addition, homo-deletion of

TAT

alleles was detected in two cases. Down-regulation of

TAT

was detected in 28/50 (56%) of HCCs, which was significantly associated with the loss of

TAT

allele and hypermethylation of

TAT

5′ CpG island (CGI) region (

P

< 0.001). Functional studies found that

TAT

has a strong tumor suppressive ability. Introduction of the

TAT

gene into HCC cell lines could effectively inhibit colony formation in soft agar, foci formation, and tumor formation in nude mice. Further study found that the tumor suppressive mechanism of

TAT

was associated with its proapoptotic role in a mitochondrial-dependent manner by promoting cytochrome-
c

release and activating caspase-9 and PARP.

Conclusion

: Taken together, our findings suggest that

TAT

plays an important suppressive role in the development and progression of HCC. Hepatology 2010
Serum Hepatitis B Surface Antigen and Hepatitis B E Antigen Titers: Disease Phase Influences Correlation With Viral Load and Intrahepatic Hepatitis B Virus Markers
Authors: Thompson Alexander J.V. , Nguyen Tin , Iser David , Ayres Anna , Jackson Kathy , Littlejohn Margaret , Slavin John , Bowden Scott , Gane Edward J. , Abbott William , Lau George K.K. , Lewin Sharon R. , Visvanathan Kumar , Desmond Paul V. , Locarnini Stephen A.
Published: February 2010

Although threshold levels for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) titers have recently been proposed to guide therapy for chronic hepatitis B (CHB), their relationship to circulating hepatitis B virus (HBV) DNA and intrahepatic HBV replicative intermediates, and the significance of emerging viral variants, remains unclear. We therefore tested the hypothesis that HBsAg and HBeAg titers may vary independently of viral replication

in vivo

. In all, 149 treatment-naïve CHB patients were recruited (HBeAg-positive, n = 71; HBeAg-negative, n = 78). Quantification of HBeAg and HBsAg was performed by enzyme immunoassay. Virological characterization included serum HBV DNA load, HBV genotype, basal core promoter (BCP)/precore (PC) sequence, and, in a subset (n = 44), measurement of intrahepatic covalently closed circular DNA (cccDNA) and total HBV DNA, as well as quantitative immunohistochemical (IHC) staining for HBsAg. In HBeAg-positive CHB, HBsAg was positively correlated with serum HBV DNA and intrahepatic cccDNA and total HBV DNA (

r

= 0.69, 0.71, 0.76,

P

< 0.01). HBeAg correlated with serum HBV DNA (

r

= 0.60,

P

< 0.0001), although emerging BCP/PC variants reduced HBeAg titer independent of viral replication. In HBeAg-negative CHB, HBsAg correlated poorly with serum HBV DNA (

r

= 0.28,

P

= 0.01) and did not correlate with intrahepatic cccDNA nor total HBV DNA. Quantitative IHC for hepatocyte HBsAg confirmed a relationship with viral replication only in HBeAg-positive patients.

Conclusion:

The correlation between quantitative HBsAg titer and serum and intrahepatic markers of HBV replication differs between patients with HBeAg-positive and HBeAg-negative CHB. HBeAg titers may fall independent of viral replication as HBeAg-defective variants emerge prior to HBeAg seroconversion. These findings provide new insights into viral pathogenesis and have practical implications for the use of quantitative serology as a clinical biomarker. (Hepatology 2010)
Traffic safety and vehicle choice: quantifying the effects of the ‘arms race’ on American roads
Authors: Li Shanjun
Published: February 2010

The increasing share of light trucks in the USA has been characterized as an ‘arms race’ where individual purchases of light trucks for better self‐protection nevertheless worsen traffic safety for society. This paper investigates the interrelation between traffic safety and vehicle choice by quantifying the effects of the arms race on vehicle demand, producer performance, and traffic safety. The analysis suggests that the accident externality of a light truck amounts to $ 2444 during vehicle lifetime and that 12% of new light trucks sold in 2006 and 204 traffic fatalities could have been attributed to the arms race. Copyright © 2010 John Wiley & Sons, Ltd.
Effect of bendiocarb on development of the chick embryo
Authors: Petrovová Eva , Maženský Dávid , Vdoviaková Katarína , Massanyi Peter , Luptáková Lenka , Smrčo Peter
Published: February 2010

Agrochemicals, including pesticides, are being used in increasing amounts in agriculture and are therefore potential environmental contaminants which may affect a variety of biological systems. The pesticide residues directly affect the embryos, disturbing their normal development and causing pathophysiological and morphological changes. We have observed embryotoxicity of cholinesterase inhibitor bendiocarb in the chick embryo. The pesticide dissolved in 10% acetone in water for injection was applied in a volume of 200 μl over the embryo through membrana papyracea at embryonic days (ED) 2, 3, 4, 5 and 10. The toxicity of bendiocarb was rather low, and lethal dose (LD50) decreased with advancing development from 0.97 mg per egg at ED 2 to 28.6 mg on ED 5. The malformations in surviving embryos were observed rarely (<2%) and occurred in both control and experimental groups. In the treatment at ED 5 and 10 there was a statistically significant reduction in body weight, but the maximum difference from controls was below 14%. In treated chick embryos on ED 3 and 4 was observed a small but not significant increase in number of dead cells using supravital staining. We conclude that bendiocarb possesses no significant toxicity in the avian embryo. Our analysis of bendiocarb embryotoxic potential in the chick embryo supports the earlier observations in other animal models, testifying to the relative safety of bendiocarb for the embryo or fetus. Copyright © 2010 John Wiley & Sons, Ltd.
Men with metabolic syndrome have lower bone mineral density but lower fracture risk—the MINOS study
Authors: Szulc Pawel , Varennes Annie , Delmas Pierre D , Goudable Joëlle , Chapurlat Roland
Published: February 2010

Data on the association of the metabolic syndrome (MetS) with bone mineral density (BMD) and fracture risk in men are inconsistent. We studied the association between MetS and bone status in 762 older men followed up for 10 years. After adjustment for age, body mass index, height, physical activity, smoking, alcohol intake, and serum 25-hydroxycholecalciferol D and 17β-estradiol levels, men with MetS had lower BMD at the hip, whole body, and distal forearm (2.2% to 3.2%, 0.24 to 0.27 SD, p < .05 to .005). This difference was related to abdominal obesity (assessed by waist circumference, waist-hip ratio, or central fat mass) but not other MetS components. Men with MetS had lower bone mineral content (3.1% to 4.5%, 0.22 to 0.29 SD, p < .05 to 0.001), whereas differences in bone size were milder. Men with MetS had a lower incidence of vertebral and peripheral fractures (6.7% versus 12.0%, p < .05). After adjustment for confounders, MetS was associated with a lower fracture incidence [odds ratio (OR) = 0.33, 95% confidence interval (CI) 0.15–0.76, p < .01]. Among the MetS components, hypertriglyceridemia was most predictive of the lower fracture risk (OR = 0.25, 95%CI 0.10–0.62, p < .005). Lower fracture risk in men with MetS cannot be explained by differences in bone size, rate of bone turnover rate and bone loss, or history of falls or fractures. Thus older men with MetS have a lower BMD related to the abdominal obesity and a lower risk of fracture related to hypertriglyceridemia. MetS probably is not a meaningful concept in the context of bone metabolism. Analysis of its association with bone-related variables may obscure the pathophysiologic links of its components with bone status. © 2010 American Society for Bone and Mineral Research
Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength
Authors: Ominsky Michael S , Vlasseros Fay , Jolette Jacquelin , Smith Susan Y , Stouch Brian , Doellgast George , Gong Jianhua , Gao Yongming , Cao Jin , Graham Kevin , Tipton Barbara , Cai Jill , Deshpande Rohini , Zhou Lei , Hale Michael D , Lightwood Daniel J , Henry Alistair J , Popplewell Andrew G , Moore Adrian R , Robinson Martyn K , Lacey David L , Simonet W Scott , Paszty Chris
Published: February 2010

The development of bone-rebuilding anabolic agents for treating bone-related conditions has been a long-standing goal. Genetic studies in humans and mice have shown that the secreted protein sclerostin is a key negative regulator of bone formation. More recently, administration of sclerostin-neutralizing monoclonal antibodies in rodent studies has shown that pharmacologic inhibition of sclerostin results in increased bone formation, bone mass, and bone strength. To explore the effects of sclerostin inhibition in primates, we administered a humanized sclerostin-neutralizing monoclonal antibody (Scl-AbIV) to gonad-intact female cynomolgus monkeys. Two once-monthly subcutaneous injections of Scl-AbIV were administered at three dose levels (3, 10, and 30 mg/kg), with study termination at 2 months. Scl-AbIV treatment had clear anabolic effects, with marked dose-dependent increases in bone formation on trabecular, periosteal, endocortical, and intracortical surfaces. Bone densitometry showed that the increases in bone formation with Scl-AbIV treatment resulted in significant increases in bone mineral content (BMC) and/or bone mineral density (BMD) at several skeletal sites (ie, femoral neck, radial metaphysis, and tibial metaphysis). These increases, expressed as percent changes from baseline were 11 to 29 percentage points higher than those found in the vehicle-treated group. Additionally, significant increases in trabecular thickness and bone strength were found at the lumbar vertebrae in the highest-dose group. Taken together, the marked bone-building effects achieved in this short-term monkey study suggest that sclerostin inhibition represents a promising new therapeutic approach for medical conditions where increases in bone formation might be desirable, such as in fracture healing and osteoporosis. © 2010 American Society for Bone and Mineral Research
A patient with severe hypercalcemia in multiple organ dysfunction syndrome: Role of elevated circulating 1α,25(OH)2vitamin D levels
Authors: Kazama Junichiro James , Yamamoto Takashi , Oya Hiroshi , Yamamoto Satoshi , Sato Yoshinobu , Sakurada Junko , Honda Tadayuki , Endoh Hiroshi , Narita Ichiei
Published: February 2010

A 54-year-old man was transferred to our ICU because of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). He died after 38 days of intensive care. During treatment, his serum calcium (Ca) levels continued to increase and reached 3.95 mmol/L, while the ionized Ca levels reached 2.30 mmol/L before his death. He presented with severe kidney injury, pancreatitis, and hemorrhagic gastric erosion that worsened his prognosis; these were possibly associated with the hypercalcemia. His circulating 1α,25-dihydroxyvitamin D [1,25(OH)2D] level was elevated (75.7 to 204 pg/mL), whereas the levels of 25-hydroxyvitamin D, parathyroid hormone, and parathyroid hormone–related peptide were not. Liver histology revealed immunoreactivity for 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1) in some of the hepatocytes, in which the localization pattern was similar to that of lysozyme-positive hepatocytes. Our ICU has previously encountered 22 similar MODS patients who presented with hypercalcemia over the last 8 years. SIRS with severe kidney and liver injuries are common clinical findings in hypercalcemic patients with MODS. Of the 23 hypercalcemic MODS patients, including the present patient, 17 had circulating 1,25(OH)2D levels exceeding 70 pg/mL despite severe kidney injury. Extrarenal activation of CYP27B1 seems to play a role in the development of hypercalcemia in this disease condition. Clinicians need to be aware that severe hypercalcemia may occur in MODS patients. © 2010 American Society for Bone and Mineral Research
Estimates of the proportion of older white men who would be recommended for pharmacologic treatment by the new US national osteoporosis foundation guidelines
Authors: Donaldson Meghan G , Cawthon Peggy M , Lui Lily Y , Schousboe John T , Ensrud Kristine E , Taylor Brent C , Cauley Jane A , Hillier Teresa A , Dam Thuy T , Curtis Jeff R , Black Dennis M , Bauer Douglas C , Orwoll Eric S , Cummings Steven R
Published: February 2010

The new US National Osteoporosis Foundation's (NOF's) Clinician's Guide to Prevention and Treatment of Osteoporosis includes criteria for recommending pharmacologic treatment based on history of hip or vertebral fracture, femoral neck or spine bone mineral density (BMD) T-scores of −2.5 or less, and presence of low bone mass at the femoral neck or spine plus a 10-year risk of hip fracture of 3% or greater or of major osteoporotic fracture of 20% or greater. The proportion of men who would be recommended for treatment by these guidelines is not known. We applied the NOF criteria for treatment to men participating in the Osteoporotic Fractures in Men Study (MrOS). To determine how the MrOS population differs from the general US population of Caucasian men aged 65 years and older, we compared men in MrOS with men who participated in the National Health and Nutrition Examination Survey (NHANES) III on criteria included in the NOF treatment guidelines that were common to both cohorts. Compared with NHANES III, men in MrOS had higher femoral neck BMD values. Application of NOF guidelines to MrOS data estimated that at least 34% of US white men aged 65 years and older and 49% of those aged 75 years and older would be recommended for drug treatment. Application of the new NOF guidelines would result in recommending a very large proportion of white men in the United States for pharmacologic treatment of osteoporosis, for many of whom the efficacy of treatment is unknown. © 2010 American Society for Bone and Mineral Research
Phosphoproteome reveals an atlas of protein signaling networks during osteoblast adhesion
Authors: Milani Renato , Ferreira Carmen V. , Granjeiro José M. , Paredes‐Gamero Edgar J. , Silva Rodrigo A. , Justo Giselle Z. , Nader Helena B. , Galembeck Eduardo , Peppelenbosch Maikel P. , Aoyama Hiroshi , Zambuzzi Willian F.
Published: February 2010

Cell adhesion on surfaces is a fundamental process in the emerging biomaterials field and developmental events as well. However, the mechanisms regulating this biological process in osteoblasts are not fully understood. Reversible phosphorylation catalyzed by kinases is probably the most important regulatory mechanism in eukaryotes. Therefore, the goal of this study is to assess osteoblast adhesion through a molecular prism under a peptide array technology, revealing essential signaling proteins governing adhesion‐related events. First, we showed that there are main morphological changes on osteoblast shape during adhesion up to 3 h. Second, besides classical proteins activated upon integrin activation, our results showed a novel network involving signaling proteins such as Rap1A, PKA, PKC, and GSK3β during osteoblast adhesion on polystyrene. Third, these proteins were grouped in different signaling cascades including focal adhesion establishment, cytoskeleton rearrangement, and cell‐cycle arrest. We have thus provided evidence that a global phosphorylation screening is able to yield a systems‐oriented look at osteoblast adhesion, providing new insights for understanding of bone formation and improvement of cell–substratum interactions. Altogether, these statements are necessary means for further intervention and development of new approaches for the progress of tissue engineering. J. Cell. Biochem. 109: 957–966, 2010. © 2010 Wiley‐Liss, Inc.
Intact T cell receptor signaling by CD4+ T cells cultured in the rotating wall‐vessel bioreactor
Authors: Simons D.M. , Gardner E.M. , Lelkes P.I.
Published: February 2010

T lymphocytes fail to proliferate or secrete cytokines in response to T cell receptor (TCR) agonists during culture in spaceflight or ground‐based microgravity analogs such as rotating wall‐vessel (RWV) bioreactors. In RWVs, these responses can be rescued by co‐stimulation with sub‐mitogenic doses of the diacyl glycerol (DAG) mimetic phorbol myristate acetate. Based on this result we hypothesized that TCR activation is abrogated in the RWV due to impaired DAG signaling downstream of the TCR. To test this hypothesis we compared TCR‐induced signal transduction by primary, human, CD4+ T cells in RWV, and static culture. Surprisingly, we found little evidence of impaired DAG signaling in the RWV. Upstream of DAG, the tyrosine phosphorylation of several key components of the TCR‐proximal signal was not affected by culture in the RWV. Similarly, the phosphorylation and compartmentalization of ERK and the degradation of IκB were unchanged by culture in the RWV indicating that RAS‐ and PKC‐mediated signaling downstream of DAG are also unaffected by simulated microgravity. We conclude from these data that TCR signaling through DAG remains intact during culture in the RWV, and that the loss of functional T cell activation in this venue derives from the affect of simulated microgravity on cellular processes that are independent of the canonical TCR pathway. J. Cell. Biochem. 109: 1201–1209, 2010. © 2010 Wiley‐Liss, Inc.
Integrin‐linked kinase is involved in TNF‐α‐induced inducible nitric‐oxide synthase expression in myoblasts
Authors: Tsou Hsi‐Kai , Su Chen‐Ming , Chen Hsien‐Te , Hsieh Ming‐Han , Lin Cheng‐Jyh , Lu Dah‐Yuu , Tang Chih‐Hsin , Chen Yi‐Hung
Published: February 2010

Tumor necrosis factor‐α (TNF‐α) is a pleiotropic cytokine produced by activated macrophages. Nitric oxide (NO) is a highly reactive nitrogen radical implicated in inflammatory responses. We investigated the signaling pathway involved in inducible nitric oxide synthase (iNOS) expression and NO production stimulated by TNF‐α in cultured myoblasts. TNF‐α stimulation caused iNOS expression and NO production in myoblasts (G7 cells). TNF‐α‐mediated iNOS expression was attenuated by integrin‐linked kinase (ILK) inhibitor (KP392) and siRNA. Pretreatment with Akt inhibitor, mammalian target of rapamycin (mTOR) inhibitor (rapamycin), NF‐κB inhibitor (PDTC), and IκB protease inhibitor (TPCK) also inhibited the potentiating action of TNF‐α. Stimulation of cells with TNF‐α increased ILK kinase activity. TNF‐α also increased the Akt and mTOR phosphorylation. TNF‐α mediated an increase of NF‐κB‐specific DNA–protein complex formation, p65 translocation into nucleus, NF‐κB‐luciferase activity was inhibited by KP392, Akt inhibitor, and rapamycin. Our results suggest that TNF‐α increased iNOS expression and NO production in myoblasts via the ILK/Akt/mTOR and NF‐κB signaling pathway. J. Cell. Biochem. 109: 1244–1253, 2010. © 2010 Wiley‐Liss, Inc.
Global minimum geometries of acetylene clusters (HCCH)n with n ≤ 55 obtained by a heuristic method combined with geometrical perturbations
Authors: Takeuchi Hiroshi
Published: February 2010

Geometry optimization of acetylene clusters (HCCH)n in the range of n ≤ 55 was carried out with a recently proposed intermolecular potential consisting of Morse potentials, damped dispersion terms, and damped Coulomb terms. The heuristic method developed by the present author was used in the optimization: optimal geometries were searched by using geometry perturbations and subsequent local optimizations. The calculations were repeated until the global minimum was found for each cluster at least three times. The obtained results were analyzed to examine structural evolution of the clusters. The geometries of the clusters with n ≥ 25 were similar to the geometry in the cubic crystal of acetylene whereas smaller clusters take icosahedron‐based geometries. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
Thermodynamic stability of hydrogen‐bonded systems in polar and nonpolar environments
Authors: Pašalić Hasan , Aquino Adélia J. A. , Tunega Daniel , Haberhauer Georg , Gerzabek Martin H. , Georg Herbert C. , Moraes Tatiane F. , Coutinho Kaline , Canuto Sylvio , Lischka Hans
Published: February 2010

The thermodynamic properties of a selected set of benchmark hydrogen‐bonded systems (acetic acid dimer and the complexes of acetic acid with acetamide and methanol) was studied with the goal of obtaining detailed information on solvent effects on the hydrogen‐bonded interactions using water, chloroform, and n‐heptane as representatives for a wide range in the dielectric constant. Solvent effects were investigated using both explicit and implicit solvation models. For the explicit description of the solvent, molecular dynamics and Monte Carlo simulations in the isothermal–isobaric (NpT) ensemble combined with the free energy perturbation technique were performed to determine solvation free energies. Within the implicit solvation approach, the polarizable continuum model and the conductor‐like screening model were applied. Combination of gas phase results with the results obtained from the different solvation models through an appropriate thermodynamic cycle allows estimation of complexation free energies, enthalpies, and the respective entropic contributions in solution. Owing to the strong solvation effects of water the cyclic acetic acid dimer is not stable in aqueous solution. In less polar solvents the double hydrogen bond structure of the acetic acid dimer remains stable. This finding is in agreement with previous theoretical and experimental results. A similar trend as for the acetic acid dimer is also observed for the acetamide complex. The methanol complex was found to be thermodynamically unstable in gas phase as well as in any of the three solvents. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
Evaluation of the performance of four molecular docking programs on a diverse set of protein‐ligand complexes
Authors: Li Xun , Li Yan , Cheng Tiejun , Liu Zhihai , Wang Renxiao
Published: February 2010

Many molecular docking programs are available nowadays, and thus it is of great practical value to evaluate and compare their performance. We have conducted an extensive evaluation of four popular commercial molecular docking programs, including Glide, GOLD, LigandFit, and Surflex. Our test set consists of 195 protein‐ligand complexes with high‐resolution crystal structures (resolution ≤2.5 Å) and reliable binding data [dissociation constant (Kd) or inhibition constant (Ki)], which are selected from the PDBbind database with an emphasis on diversity. The top‐ranked solutions produced by these programs are compared to the native ligand binding poses observed in crystal structures. Glide and GOLD demonstrate better accuracy than the other two on the entire test set. Their results are also less sensitive to the starting structures for docking. Comparison of the results produced by these programs at three different computation levels reveal that their accuracy are not always proportional to CPU cost as one may expect. The binding scores of the top‐ranked solutions produced by these programs are in low to moderate correlations with experimentally measured binding data. Further analyses on the outcomes of these programs on three suites of subsets of protein‐ligand complexes indicate that these programs are less capable to handle really flexible ligands and relatively flat binding sites, and they have different preferences to hydrophilic/hydrophobic binding sites. Our evaluation can help other researchers to make reasonable choices among available molecular docking programs. It is also valuable for program developers to improve their methods further. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010