bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure of the deacetylase LpxC bound to the antibiotic CHIR-090: Time-dependent inhibition and specificity in ligand binding
Authors: Barb Adam W. , Jiang Ling , Raetz Christian R. H. , Zhou Pei
Published: November 2007

The UDP-3-
O
-(
R
-3-hydroxyacyl)-
N
-acetylglucosamine deacetylase LpxC is an essential enzyme of lipid A biosynthesis in Gram-negative bacteria and a promising antibiotic target. CHIR-090, the most potent LpxC inhibitor discovered to date, displays two-step time-dependent inhibition and kills a wide range of Gram-negative pathogens as effectively as ciprofloxacin or tobramycin. In this study, we report the solution structure of the LpxC–CHIR-090 complex. CHIR-090 exploits conserved features of LpxC that are critical for catalysis, including the hydrophobic passage and essential active-site residues. CHIR-090 is adjacent to, but does not occupy, the UDP-binding pocket of LpxC, suggesting that a fragment-based approach may facilitate further optimization of LpxC inhibitors. Additionally, we identified key residues in the Insert II hydrophobic passage that modulate time-dependent inhibition and CHIR-090 resistance. CHIR-090 shares a similar, although previously unrecognized, chemical scaffold with other small-molecule antibiotics such as L-161,240 targeting LpxC, and provides a template for understanding the binding mode of these inhibitors. Consistent with this model, we provide evidence that L-161,240 also occupies the hydrophobic passage.
Technological Change and the Form of Science Research Teams: Dealing with the Digitals
Authors: Meyer Eric T.
Published: November 2007

During the late 1990s, photography moved from being a primarily analogue medium to being an almost entirely digital medium. The development of digital cameras and software for working with photographs has led to the wholesale computerization of photography in many different domains. This paper reports on the findings of a study of the social and organizational changes experienced by marine mammal scientists who have changed from film‐based photography to digital photography. This technical change might be viewed as a simple substitution of a digital for an analogue camera, with little significance for how scientists do what they do. However, a perspective anchored in social informatics leads to the expectation that such incremental technical changes can have significant outcomes, changing not only how scientists work, but also the outcomes of their research. This present study finds that key consequences of this change have been the composition of the personnel working on the scientific research teams for marine biology projects and the ways in which these scientists allocate their time.
The Use of Touch‐Screen Technology for Health‐Related Information in Indigenous Communities: Some Economic Issues
1
Authors: Doessel D. P. , Travers Helen , Hunter Ernest
Published: November 2007

The low health status of indigenous communities in Australia, and other countries, has been a continuing societal problem. One way to improve health status involves the provision of health‐related information. Computer‐based systems offer new ways to provide such information: thus their application can be seen as process innovations. This paper describes the use of touch‐screen technology to present health information in a culturally relevant fashion for Aboriginal and Torres Strait Islanders in Queensland, Australia. Touch‐screen kiosks incorporate both computer hardware and software. The paper also outlines some of the key economic concepts relevant to an economic analysis of an information system employing touch‐screen technology. It is shown that the economic analysis involves a two‐stage process, and it is somewhat more complex than setting up an Internet website.
Review Article: The Rise of Studying Happiness, but what of the Shadow of Unhappiness from Mental Illness?
1
Authors: Doessel D. P.
Published: November 2007

This essay is concerned with describing some issues associated with a relatively recent development in economics, viz. the economics of happiness literature. After providing a very brief account of the history of the concept of happiness, and the recent literature in economics, the focus turns to two issues that have been relatively neglected. First, there has been little attention in this recent literature to the concept of virtue or a flourishing life, or a moral disposition to happiness. Second, it is argued that the focus on aggregate happiness for a society in general may be misplaced: focus on subgroups, such as the mentally ill, may be more appropriate.
Republicans and Socialists and the Origins of Italian Political Parties
Authors: Morisi Paolo
Published: November 2007

A central debate in political science centres on the origins of political parties and specifically on the question as to whether they emerged as a result of the rise of parliamentary institutions. Regarding the Italian party system, the commonly held view is that Italian parties emerged as a consequence of national unification and the establishment of parliament. This article contributes to the debate on the origins of Italian parties by presenting empirical evidence on the timing of their initial formation, analysing data regarding the social base, membership, organisational articulation and policy-making accomplishments of the two major political movements active before and after the establishment of the national parliament. The article argues that, at least in the Italian case, parties did not originate in the legislature; rather, similar to countries such as Germany and Spain, Italian parties developed as a result of a major national crisis.
The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions
Authors: Nahrendorf Matthias , Swirski Filip K. , Aikawa Elena , Stangenberg Lars , Wurdinger Thomas , Figueiredo Jose-Luiz , Libby Peter , Weissleder Ralph , Pittet Mikael J.
Published: November 2007

Healing of myocardial infarction (MI) requires monocytes/macrophages. These mononuclear phagocytes likely degrade released macromolecules and aid in scavenging of dead cardiomyocytes, while mediating aspects of granulation tissue formation and remodeling. The mechanisms that orchestrate such divergent functions remain unknown. In view of the heightened appreciation of the heterogeneity of circulating monocytes, we investigated whether distinct monocyte subsets contribute in specific ways to myocardial ischemic injury in mouse MI. We identify two distinct phases of monocyte participation after MI and propose a model that reconciles the divergent properties of these cells in healing. Infarcted hearts modulate their chemokine expression profile over time, and they sequentially and actively recruit Ly-6Chi and -6Clo monocytes via CCR2 and CX3CR1, respectively. Ly-6Chi monocytes dominate early (phase I) and exhibit phagocytic, proteolytic, and inflammatory functions. Ly-6Clo monocytes dominate later (phase II), have attenuated inflammatory properties, and express vascular–endothelial growth factor. Consequently, Ly-6Chi monocytes digest damaged tissue, whereas Ly-6Clo monocytes promote healing via myofibroblast accumulation, angiogenesis, and deposition of collagen. MI in atherosclerotic mice with chronic Ly-6Chi monocytosis results in impaired healing, underscoring the need for a balanced and coordinated response. These observations provide novel mechanistic insights into the cellular and molecular events that regulate the response to ischemic injury and identify new therapeutic targets that can influence healing and ventricular remodeling after MI.
Estimating node degree in bait-prey graphs
Authors: Scholtens Denise , Chiang Tony , Huber Wolfgang , Gentleman Robert
Published: November 2007

Motivation: Proteins work together to drive biological processes in cellular machines. Summarizing global and local properties of the set of protein interactions, the interactome, is necessary for describing cellular systems. We consider a relatively simple per-protein feature of the interactome: the number of interaction partners for a protein, which in graph terminology is the degree of the protein.

Results: Using data subject to both stochastic and systematic sources of false positive and false negative observations, we develop an explicit probability model and resultant likelihood method to estimate node degree on portions of the interactome assayed by bait-prey technologies. This approach yields substantial improvement in degree estimation over the current practice that naïvely sums observed edges. Accurate modeling of observed data in relation to true but unknown parameters of interest gives a formal point of reference from which to draw conclusions about the system under study.

Availability: All analyses discussed in this text can be performed using the ppiStats and ppiData packages available through the Bioconductor project (http://www.bioconductor.org).

Contact:  dscholtens@northwestern.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
Effects of symmetry crossover in quantum transport in graphene and nanotubes
Authors: Ando Tsuneya
Published: November 2007

A brief review is given here on transport properties of carbon nanotubes mainly from a theoretical point of view. The topics include an effective-mass description of electronic states and the absence of backscattering and the presence of a perfectly conducting channel except for scatterers with a potential range smaller than the lattice constant. The dynamical conductivity in the presence of a perfect channel and effects of symmetry crossover are also discussed.
Forms and behaviour of vacuum emission electronic devices comprising diamond or other carbon cold cathode emitters
Authors: Davidson J.L , Kang W.P , Subramanian K , Wong Y.M
Published: November 2007

Nanocarbon-derived electron emission devices, specifically nanodiamond lateral field emission (FE) diodes and gated carbon nanotube (CNT) triodes, are new configurations for robust nanoelectronic devices. These novel micro/nanostructures provide an alternative and efficient means of accomplishing electronics that are impervious to temperature and radiation. For example, nitrogen-incorporated nanocrystalline diamond has been lithographically micropatterned to use the material as an electron field emitter. Arrays of laterally arranged ‘finger-like’ nanodiamond emitters constitute the cathode in a versatile diode configuration with a small interelectrode separation. A low diode turn-on voltage of 7 V and a high emission current of 90 μA at an anode voltage of 70 V (electric field of approx. 7 V μm
−1
) are reported for the nanodiamond lateral device. Also, a FE triode amplifier based on aligned CNTs with a low turn-on voltage and a small gate leakage current has been developed.
Saturation mutagenesis of Asn152 reveals a substrate selectivity switch in P99 cephalosporinase
Authors: Lefurgy Scott T. , de Jong René M. , Cornish Virginia W.
Published: November 2007

In class C β‐lactamases, the strictly conserved Asn152 forms part of an extended active‐site hydrogen‐bonding network. To probe its role in catalysis, all 19 mutants of Enterobacter cloacae P99 cephalosporinase Asn152 were simultaneously constructed and screened in Escherichia coli for their in vivo activity. The screen identified the previously uncharacterized mutants Asn152Ser, Asn152Thr, and Asn152Gly, which possess significant activity and altered substrate selectivity. In vitro measurement of Michaelis‐Menten kinetic constants revealed that the Asn152Ser mutation causes a selectivity switch for penicillin G versus cefoxitin. Asn152Thr showed a 63‐fold increase in kcat for oxacillin, a slow substrate for wild‐type cephalosporinase. The results contribute to a growing body of data showing that mutation of highly conserved residues in the active site can result in substrate selectivity changes. The library screening method presented here would be applicable to substrate selectivity determination in other readily screenable enzymes.
Large‐scale preparation of the homogeneous LolA–lipoprotein complex and efficient in vitro transfer of lipoproteins to the outer membrane in a LolB‐dependent manner
Authors: Watanabe Shoji , Oguchi Yuki , Yokota Naoko , Tokuda Hajime
Published: November 2007

An ATP‐binding cassette transporter LolCDE complex of Escherichia coli releases lipoproteins destined to the outer membrane from the inner membrane as a complex with a periplasmic chaperone, LolA. Interaction of the LolA–lipoprotein complex with an outer membrane receptor, LolB, then causes localization of lipoproteins to the outer membrane. As far as examined, formation of the LolA–lipoprotein complex strictly depends on ATP hydrolysis by the LolCDE complex in the presence of LolA. It has been speculated, based on crystallographic and biochemical observations, that LolA undergoes an ATP‐dependent conformational change upon lipoprotein binding. Thus, preparation of a large amount of the LolA–lipoprotein complex is difficult. Moreover, lipoproteins bound to LolA are heterogeneous. We report here that the coexpression of LolA and outer membrane‐specific lipoprotein Pal from a very efficient plasmid causes the unusual accumulation of the LolA–Pal complex in the periplasm. The complex was purified to homogeneity and shown to be a functional intermediate of the lipoprotein localization pathway. In vitro incorporation of Pal into outer membranes revealed that a single molecule of LolB catalyzes the incorporation of more than 100 molecules of Pal into outer membranes. Moreover, the LolB‐dependent incorporation of Pal was not affected by excess‐free LolA, indicating that LolB specifically interacts with liganded LolA. Finally, the LolB depletion caused the accumulation of a significant amount of Pal in the periplasm, thereby establishing the conditions for preparation of the homogeneous LolA–lipoprotein complex.
Characterization of the binding surface of the translocated intimin receptor, an essential protein for EPEC and EHEC cell adhesion
Authors: Ross Nathan T. , Miller Benjamin L.
Published: November 2007

The translocated intimin receptor (TIR) of enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC) is required for EPEC and EHEC infections, which cause widespread illness across the globe. TIR is translocated via a type‐III secretion system into the intestinal epithelial cell membrane, where it serves as an anchor for E. coli attachment via its binding partner intimin. While many aspects of EPEC and EHEC infection are now well understood, the importance of the intermolecular contacts made between intimin and TIR have not been thoroughly investigated. Herein we report site‐directed mutagenesis studies on the intimin‐binding domain of EPEC TIR, and how these mutations affect TIR‐intimin association, as analyzed by isothermal titration calorimetry and circular dichroism. These results show how two factors govern TIR's binding to intimin: A three‐residue TIR hot spot is identified that largely mediates the interaction, and mutants that alter the β‐hairpin structure of TIR severely diminish binding affinity. In addition, peptides incorporating key TIR residues identified by mutagenesis are incapable of binding intimin. These results indicate that hot spot residues and structural orientation/preorganization are required for EPEC, and likely EHEC, TIR‐intimin binding.
The Staphylococcus aureus extracellular adherence protein (Eap) adopts an elongated but structured conformation in solution
Authors: Hammel Michal , Němeček Daniel , Keightley J. Andrew , Thomas George J. , Geisbrecht Brian V.
Published: November 2007

The extracellular adherence protein (Eap) of Staphylococcus aureus participates in a wide range of protein–protein interactions that facilitate the initiation and dissemination of Staphylococcal disease. In this report, we describe the use of a multidisciplinary approach to characterize the solution structure of full‐length Eap. In contrast to previous reports suggesting that a six‐domain isoform of Eap undergoes multimerization, sedimentation equilibrium analytical ultracentrifugation data revealed that a four‐domain isoform of Eap is a monomer in solution. In vitro proteolysis and solution small angle X‐ray scattering studies both indicate that Eap adopts an extended conformation in solution, where the linkers connecting sequential EAP modules are solvent exposed. Construction of a low‐resolution model of full‐length Eap using a combination of ab initio deconvolution of the SAXS data and rigid body modeling of the EAP domain crystal structure suggests that full‐length Eap may present several unique concave surfaces capable of participating in ligand binding. These results also raise the possibility that such surfaces may be held together by additional interactions between adjacent EAP modules. This hypothesis is supported by a comparative Raman spectroscopic analysis of full‐length Eap and a stoichiometric solution of the individual EAP modules, which indicates the presence of additional secondary structure and a greater extent of hydrogen/deuterium exchange protection in full‐length Eap. Our results provide the first insight into the solution structure of full‐length Eap and an experimental basis for interpreting the EAP domain crystal structures within the context of the full‐length molecule. They also lay a foundation for future studies into the structural and molecular bases of Eap‐mediated protein–protein interactions with its many ligands.
Personality differences in monozygotic twins discordant for cannabis use
Authors: Vink Jacqueline M. , Nawijn Laura , Boomsma Dorret I. , Willemsen Gonneke
Published: November 2007

Aims  To explore the association between cannabis and personality scores when genetic background and shared environment are controlled for.

Design  The co‐twin control design. This design provides a powerful method for controlling for the effects of potentially confounding familial factors that may act to predispose subjects both to cannabis use and a particular personality profile.

Participants  118 monozygotic twin pairs discordant for cannabis use.

Measurements  Data on personality and cannabis use were obtained through a questionnaire survey. The Dutch Sensation Seeking List was used to assess various aspects of sensation seeking. The Amsterdamse Biografische Vragenlijst assessed extraversion, neuroticism, somatic complaints and test attitude.

Findings  The affected twins scored higher on all scales than their unaffected co‐twins, especially on experience seeking (P = 0.004), total sensation seeking score (P = 0.004) and neuroticism (P = 0.039). Differences were also observed when items on drug use were removed from the experience seeking scale (P = 0.037) and total sensation seeking score (P = 0.009) although these differences were no longer significant after Bonferoni correction (P < 0.005).

Conclusions  Cannabis use is associated with a higher score on personality scales. This result was obtained in a sample of monozygotic twins discordant for cannabis use. Thus, at least part of the association between cannabis use and experience seeking cannot be attributed to underlying genetic or shared environmental factors that influence both personality and cannabis use and must be explained by unique environmental influences.
Varenicline in the routine treatment of tobacco dependence: a pre–post comparison with nicotine replacement therapy and an evaluation in those with mental illness
Authors: Stapleton John A. , Watson Lucy , Spirling Lucy I. , Smith Robert , Milbrandt Andrea , Ratcliffe Marina , Sutherland Gay
Published: November 2007

Aims  To compare the effectiveness of varenicline with nicotine replacement for smoking cessation and to evaluate the safety and effectiveness of varenicline in people with mental illness.

Design  Evaluation of consecutive routine cases before and after the introduction of varenicline.

Setting  National Health Service (NHS) tobacco dependence clinic in London, UK.

Participants  A total of 412 cases receiving routine care.

Intervention  Seven group support sessions over 6 weeks with either nicotine replacement therapy (NRT) (n = 204) or varenicline (n = 208).

Measurements  Verified abstinence 4 weeks after quit day, severity of withdrawal symptoms, incidence and severity of adverse drug symptoms, cost per patient treated and cost per successful short‐term quitter.

Findings  Short‐term cessation rates were higher with varenicline than NRT (odds ratio = 1.70, 95% confidence interval = 1.09–2.67). Varenicline was equally effective in those with and without mental illness. Craving to smoke, but not adverse mood, was less severe with varenicline than NRT. The cost per quitter was similar for varenicline and NRT. There was a higher incidence of adverse drug symptoms among those taking varenicline, but these were tolerated by most smokers. There was no evidence that varenicline exacerbated mental illness.

Conclusions  In this setting and with group support varenicline appears to improve success rates over those achieved with NRT, and is equally effective and safe in those with and without a mental illness.
Inferior outcomes for overweight children undergoing allogeneic stem cell transplantation
Authors: Bulley Sean , Gassas Adam , Dupuis L. Lee , Aplenc Richard , Beyene Joseph , Greenberg Mark L , Doyle John J , Sung Lillian
Published: November 2007

This retrospective cohort study aimed at determining whether overweight children undergoing allogeneic stem cell transplantation (SCT) had inferior overall survival compared with children who were not overweight. Children ≥2 years of age who received allogeneic SCT were included. Overweight was defined as a body mass index ≥ 95th percentile; 54/325 (17%) children were overweight. Overall survival at 5 years was significantly inferior at 46·6 ± 7·3% in the overweight group compared with 59·5 ± 3·2% in the non‐overweight group (P = 0·02). Our study demonstrated that overweight children who undergo allogeneic SCT had inferior survival compared with children who were not overweight.
The GOAL study: a prospective examination of the impact of factor V Leiden and ABO(H) blood groups on haemorrhagic and thrombotic pregnancy outcomes
Authors: Clark Peter , Walker Isobel D. , Govan Lindsay , Wu Olivia , Greer Ian A.
Published: November 2007

Factor V Leiden (FVL) and ABO(H) blood groups are the common influences on haemostasis and retrospective studies have linked FVL with pregnancy complications. However, only one sizeable prospective examination has taken place. As a result, neither the impact of FVL in unselected subjects, any interaction with ABO(H) in pregnancy, nor the utility of screening for FVL is defined. A prospective study of 4250 unselected pregnancies was carried out. A venous thromboembolism (VTE) rate of 1·23/1000 was observed, but no significant association between FVL and pre‐eclampsia, intra‐uterine growth restriction or pregnancy loss was seen. No influence of FVL and/or ABO(H) on ante‐natal bleeding or intra‐partum or postpartum haemorrhage was observed. However, FVL was associated with birth‐weights >90th centile [odds ratio (OR) 1·81; 95% confidence interval (CI95) 1·04–3·31] and neonatal death (OR 14·79; CI95 2·71–80·74). No association with ABO(H) alone, or any interaction between ABO(H) and FVL was observed. We neither confirmed the protective effect of FVL on pregnancy‐related blood loss reported in previous smaller studies, nor did we find the increased risk of some vascular complications reported in retrospective studies.
Drug allergy claims in children: from self‐reporting to confirmed diagnosis
Authors: Rebelo Gomes E. , Fonseca J. , Araujo L. , Demoly P.
Published: November 2007

BackgroundPoorly documented self‐reported drug allergy (DAll) is a frequent problem in daily clinical practice and has a considerable impact on prescription choices. The diagnostic work‐up of drug hypersensitivity (DHs) allows a better classification of the reactions and provides patients with more reliable information and recommendations for future treatments.

ObjectiveTo assess the prevalence of self‐reported adverse drug reactions (ADRs) and DAll in a paediatric population and to investigate children reporting suspected DAll in order to achieve a firm diagnosis.

DesignThe first phase was based on a cross‐sectional survey assessing the life occurrence of ADRs and self‐reported DAll carried out at the outpatient clinic of a paediatric hospital. The second phase was based on the diagnostic work‐up in children with parent‐reported DAll, including detailed anamnesis andin vitroandin vivoinvestigations (skin and provocation tests).

ParticipantsOne thousand four hundred and twenty‐six parents responded to the initial survey. Sixty of the 67 patients with reported DAll were evaluated at the allergy clinic.

ResultsThe prevalences of self‐reported ADRs and DAll were 10.2% and 6.0%, respectively. Most of the suspected allergic reactions were non‐immediate cutaneous events attributable to β‐lactam antibiotics and occurred in very young children. Thirty‐nine of the 60 patients consulting for evaluation had a plausible clinical history and were recommended further investigation. DHs was diagnosed in three children only, based on positive responses in skin (n=1) and oral provocation (n=2) tests.

ConclusionADRs are frequently reported in children, and many children are classified as having a DAll. After complete evaluation, only a few of these reactions can be attributed to DHs and DAll. Most of the patients (94% in this study) could actually tolerate the initially suspected drug.
Immunologic analysis of monoclonal and immunoglobulin E antibody epitopes on natural and recombinant Amb a 1
Authors: Wopfner N. , Bauer R. , Thalhamer J. , Ferreira F. , Chapman M.
Published: November 2007

Background
Amb a 1 is the major allergen from ragweed pollen and more than 90% of ragweed‐allergic patients react with this protein. Although Amb a 1 was cloned and sequenced in 1991, little is known of the specificity of anti‐Amb a 1 antibodies or of the immunologic properties of the recombinant allergen.

Objective
To compare binding of monoclonal antibodies (mAb) and IgE antibodies to purified natural Amb a 1 (nAmb a 1) and recombinant Amb a 1 (rAmb a 1).

Methods
Binding of a panel of anti‐Amb a 1 mAb and IgE antibodies to nAmb a 1 or rAmb a 1 was compared by immunoblotting. Chimeric ELISA was used to measure specific IgE to these allergens using 89 ragweed‐allergic sera from Austria, Italy, Canada and the United States.

Results
The 8 mAb bound to a 38 kDa Amb a 1 band in ragweed pollen extract and a subset of 5 mAb also bound to the 26 kDa chain of nAmb a 1. A two‐site ELISA was developed using a mAb pair, which was ∼10‐fold more sensitive to rAmb a 1. There was a significant correlation between IgE antibody binding to nAmb a 1 and rAmb a 1 (n=89, r=0.79, P<0.001). A subset of ∼40% of patients showed greater reactivity to nAmb a 1 than to rAmb a 1.

Conclusions
The data suggest that there is less reactivity of human IgE to rAmb a 1 compared with nAmb a 1. The development of more sensitive, quantitative ELISA for Amb a 1 will require the production of new mAb especially directed against nAmb a 1.
Molecular characterization of five Italian families with inherited severe factor XIII deficiency
Authors: CASTAMAN G. , GIACOMELLI S. H. , IVASKEVICIUS V. , SCHROEDER V. , KOHLER H. P. , DRAGANI A. , BIASIOLI C. , OLDENBURG J. , MADEO D. , RODEGHIERO F.
Published: November 2007

Summary.  Factor XIII (FXIII) deficiency is a very rare (1:2 000 000) severe autosomal recessive bleeding disorder, mostly due to mutations in the coagulation FXIII A‐subunit gene. We have studied the molecular basis of FXIII deficiency in five unrelated Italian families. The coding region, intron–exon boundaries and 5′‐ and 3′‐untranslated regions of the FXIII gene encoding the A subunit were amplified and directly sequenced. Candidate mutations were identified in all the patients. Three novel mutations occurred in three patients. These include a novel homozygous deletion of two base pairs (bp) in exon 14 (c.2002–2003 DelCT). This deletion causes a frameshift from Leu667 and the formation of a stop codon at amino acid position 681. The second patient presents a novel homozygous (c.2126 G>A) transition in exon 15, predicting a Ser708Asn in Barrel 2 domain. The third patient is compound heterozygote for two missense mutations, a previously reported Arg260His substitution, and a novel transition in exon 4 (c.560 C>T) predicting a Pro186Leu in the core domain. The remaining two patients have two previously reported mutations: a 4‐bp homozygous deletion in exon 11 (c.1392–1395 Del AATT), previously reported to occur in the Vicenza Area, and a homozygous nonsense mutation in exon 8 (c.979 C>T) predicting an Arg326X in the core domain. The novel mutations occurred at amino acid residues highly conserved among different species (pig, monkey, mouse and dog) and were not detected in 110 normal alleles. Structural analysis shows that Pro186Leu mutation leads to the replacement of the rigid proline pyrrolidine ring by the larger and more flexible leucine side chain and Ser708Asn may probably disrupt the hydrogen bond with Ala291.
A subset of dendritic cells express joining chain (J‐chain) protein
Authors: Källberg Eva , Leanderson Tomas
Published: November 2007

Joining chain (J‐chain) is well known as an integrated component of dimeric immunoglobulin A (IgA) and pentameric IgM. We show here that the J‐chain protein is also expressed in a subset of CD11c+ dendritic cells (DC) in C57BL/6 mice. J‐chain knockout mice (J−/− mice) had a reduced fraction of CD4−/CD8α+ and mPDCA‐1+ DC in the spleen. J−/− mice also had reduced levels of RNA for the immunoregulatory enzyme indoleamine 2,3‐dioxygenase (IDO) in the spleen. Furthermore, in lymph nodes from C57BL/6 mice the majority of J‐chain‐expressing CD11c+ cells also expressed IDO, while the number of IDO‐expressing cells in lymph nodes and the amount of IDO protein in splenic CD11c+ cells were reduced in J−/− mice. Also, J−/− mice had a lower ratio of kynurenine/tryptophan in serum compared to C57BL/6 mice, indicating a lower overall IDO activity in J−/− mice. We also show that J−/− mice are less susceptible to tolerance induction than C57BL/6 mice. In conclusion, our data show that J‐chain protein is expressed outside the B‐cell compartment in a subset of immunoregulatory DC that are compromised in animals that cannot express J‐chain.
Idiopathic generalized apical root resorption: a report of three cases
Authors: McMULLIN AILBHE , FLEMING PADHRAIG S. , DiBIASE ANDREW T.
Published: November 2007

Background.  Idiopathic apical root resorption usually presents as a chance radiographic finding. It may be widespread, affecting the majority of teeth, with implications for the longevity of the dentition.

Case report.  Three cases of significant idiopathic apical resorption resulting, respectively, in prevention, abandonment, and alternative methods of orthodontic treatment are described.

Conclusion.  Significant idiopathic resorption may present as a chance radiographic finding, as pain, or excessive mobility. The prognosis for affected teeth is often poor with very limited scope for orthodontic movement due to the likelihood of uncontrolled resorption. Definitive prosthetic rehabilitation is often best deferred until adulthood due to the potential for further resorption during adolescence in addition to vertical growth considerations.
Size distribution, density and disturbance in two Mediterranean gorgonians: Paramuricea clavata and Eunicella singularis
Authors: Linares Cristina , Coma Rafel , Garrabou Joaquim , Díaz David , Zabala Mikel
Published: November 2007

Gorgonians are long‐lived engineering species and their conservation is crucial to maintaining the biodiversity of marine communities. The slow dynamics displayed by these species make them especially vulnerable when faced with increasing disturbances.

The sessile nature and structural role of gorgonians provide several ecological similarities with trees, allowing the application of different approaches developed by forest ecology studies to overcome the constraint of long time‐scales to collect valuable dynamic data. Using these approaches, we examined the distribution and demography of two representative Mediterranean gorgonian species, Paramuricea clavata and Eunicella singularis, along a regional spatial scale as well as their response to disturbances.

The regular spatial distribution and the upper distribution limit of E. singularis suggest that this species is more tolerant to a wide range of environmental conditions than P. clavata, which exhibited a more asymmetrical spatial distribution and variation in the upper distribution limit on the latitudinal scale.

Size distributions of both species showed contrasting population dynamics. The size distribution of E. singularis was characterized by initial stages of populations (0–10 cm) in contrast to the scarcity of this stage displayed by P. clavata. This suggests differences in recruitment between species. Furthermore, only P. clavata populations displayed a strong negative correlation between density and biomass with a slope close to –3/2, indicating a self‐thinning mechanism and therefore the existence of a carrying capacity. This result and the trajectories of disturbed populations below the self‐thinning line revealed this approach as a useful method to identify the effects of biological or physical disturbance.

Synthesis and applications. The approaches used in this study provide insights into management needs in face of the difficulty of having to deal with the population dynamics of very slow‐growing threatened species. In particular, gorgonian populations can be used as an indicator of the effects of climatic anomalies on the coralligenous community.
A new paradigm in leaf‐level photosynthesis: direct and diffuse lights are not equal
Authors: BRODERSEN CRAIG R. , VOGELMANN THOMAS C. , WILLIAMS WILLIAM E. , GORTON HOLLY L.
Published: November 2007

Global‐change scenarios suggest a trend of increasing diffuse light due to expected increases in cloud cover. Canopy‐level measurements of plant‐community photosynthesis under diffuse light show increased productivity attributed to more uniform distribution of light within the forest canopy, yet the effect of the directional quality of light at the leaf level is unknown. Here we show that leaf‐level photosynthesis in sun leaves of both C3 and C4 plants can be 10–15% higher under direct light compared to equivalent absorbed irradiances of diffuse light. High‐light‐grown leaves showed significant photosynthetic enhancement in direct light, while shade‐adapted leaves showed no preference for direct or diffuse light at any irradiance. High‐light‐grown leaves with multiple palisade layers may be adapted to better utilize direct than diffuse light, while shade leaf structure does not appear to discriminate light based on its directionality. Based upon our measurements, it appears that leaf‐level and canopy‐level photosynthetic processes react differently to the directionality of light, and previously observed increases in canopy‐level photosynthesis occur even though leaf‐level photosynthesis decreases under diffuse light.
Global movement and population biology of Mycosphaerella nubilosa infecting leaves of cold‐tolerant Eucalyptus globulus and E. nitens
Authors: Hunter G. C. , Van Der Merwe N. A. , Burgess T. I. , Carnegie A. J. , Wingfield B. D. , Crous P. W. , Wingfield M. J.
Published: November 2007

Using 10 polymorphic DNA‐based microsatellite markers, the genetic diversity of eight Mycosphaerella nubilosa populations from Eucalyptus, comprising 497 isolates from five different countries, was studies using a hierarchical sampling regime. Mycosphaerella nubilosa from eastern Australia (New South Wales) had higher gene (0·506) and genotypic (76%) diversity than other populations, supporting the view that this represents the origin of the pathogen. It was also evident that M. nubilosa populations from Europe and Tanzania were clonal, with the same multilocus haplotypes occurring in South Africa, but being absent in Australia. This suggests that M. nubilosa may have been introduced into Europe via Africa, with a pathway of gene flow from Australia to South Africa, further into Africa and finally to Europe.
Berry infection and the development of bunch rot in grapes caused by Aspergillus carbonarius
Authors: Kazi B. A. , Emmett R. W. , Nancarrow N. , Partington D. L.
Published: November 2007

The effects of different levels of inoculum of Aspergillus carbonarius and time of inoculation on berry infection and the development of aspergillus bunch rot on grapevines (cv. Sultana) were studied under field conditions. Inflorescences at full bloom were inoculated with aqueous spore suspensions of A. carbonarius containing 0 or 1 × 106 spores mL−1 in 2004/05 and 0, 1 × 102 or 1 × 105 spores mL−1 in 2005/06. In both years, the incidence of infection in inoculated berries was significantly higher than in uninoculated berries. Incidence of infection in berries from veraison until harvest was higher than at earlier stages of bunch development (berry set to berries that were still hard and green). Inoculation of bunches at veraison did not significantly increase A. carbonarius infection prior to harvest, at harvest, 6 days after harvest or when berries were over‐ripe. Bunches inoculated at harvest did not significantly increase infection 6 days after harvest or when berries were over‐ripe. Aspergillus carbonarius was isolated more frequently from the pedicel end (53·1%) than from the middle section (37·5%) and distal end (35·0%) of berries that were inoculated with 105 spores mL−1.
Complications related to blood donation: a population‐based study
Authors: Sorensen B. S. , Johnsen S. P. , Jorgensen J.
Published: November 2007

Background  Population‐based data on the rate and outcome of complications related to blood donation are sparse.

Study Design and Methods  Data from a survey conducted in 2003 in Aarhus County, Denmark, were used to assess the overall rate of donor complications. Additional nationwide data on moderate and severe donor complications were obtained from the Danish Register of Complications Related to Blood Donation, with records of all moderate and severe donor complications in Denmark occurring during the period 1997–2003.

Results  In the regional survey, we identified 340 complications of any type among 41 274 donations, corresponding to a rate of 824/100 000 donations [95% confidence interval (CI): 741–916]. All complications were either needle injuries or vasovagal reactions. In the nationwide register, a total of 752 moderate and severe complications were recorded among 2 575 264 donations, corresponding to a rate of 29/100 000 donations (95% CI: 27–31). The rates of complications leading to long‐term morbidity or disablement (> 5% loss of working capacity) were 5/100 000 donations (95% CI: 4·2–5·9) and 2·3/100 000 donations (95% CI: 1·8–2·9), respectively.

Conclusion  The risk of complications related to blood donation is low. However, attention towards donor complications is warranted, given the non‐negligible rate of complications resulting in long‐term morbidity and disablement.
Post‐thaw viable CD34+ cell count is a valuable predictor of haematopoietic stem cell engraftment in autologous peripheral blood stem cell transplantation
Authors: Lee S. , Kim S. , Kim H. , Baek E. J. , Jin H. , Kim J. , Kim H. O.
Published: November 2007

Background and Objectives  In peripheral blood stem cell transplantation, the number of CD34+ cells infused is considered a predictor of haematopoietic engraftment. However, the currently accepted minimal threshold of CD34+ cells/kg was determined by counting CD34+ cells before freezing, and the loss of viable CD34+ cells during freezing, cryopreservation or thawing prior to reinfusion has not been assessed.

Materials and Methods  Total and viable CD34+ cells were quantified using single platform flow cytometry and viability dye, 7‐amino actinomycin D (7‐ADD), at the time of collection and prior to reinfusion in 46 peripheral haematopoietic stem cell grafts from 36 patients. The time to engraftment of neutrophil and platelet was assessed by routine peripheral blood cell counts performed daily.

Results  The median number of viable CD34+ cells harvested was 3·6 × 106/kg (range 0·05–21·2), and the median viability was 98% (range 70–100%) before freezing. After thawing, the median number of viable CD34+ cells was reduced to 2·2 × 106/kg (range 0·04–14·8) and the median viability was reduced to 71% (range 31–89%). The number of viable CD34+ cells/kg before freezing and after thawing significantly correlated with engraftment of neutrophils (P < 0·0001 both) and platelets (P = 0·007 and 0·006, respectively). Although the minimum dose for engraftment (2·0 × 106 CD34+ cells/kg) was harvested in 37 of 46 cases (85%), only 25 cases (54%) met this threshold at the time of reinfusion. For platelet engraftment, determination of viable CD34+ cells prior to reinfusion was more important than enumeration at the time of collection.

Conclusion  Quantification of post‐thaw viable CD34+ cells better represents the actual composition of the graft and may be a more accurate predictor of haematopoietic engraftment than post‐thaw total CD34+ cell counts, or prefreeze determinations, especially for platelet engraftment. It is necessary to develop good quality controls for freezing and thawing procedures to minimize variance in cell viability.
Occurrence and decay patterns of common wood‐decay fungi in hazardous trees felled in the Helsinki City
Authors: Terho M. , Hantula J. , Hallaksela A.‐M.
Published: November 2007

To improve the management of ageing urban trees, the role of wood‐decay fungi as potential causes of stem breakage was investigated among hazardous trees removed in the Helsinki City area during 2001–2004. The study material comprised 194 trees, and included 76 Tilia spp. trees, 58 Betula spp. and 60 Acer spp. Thirteen species or genera of commonly occurring decay fungi were identified on the basis of fruiting bodies and pure cultures. The occurrence of the fungi was investigated in terms of frequency, visibility and as potential causes for stem breakage. Most hazardous fungi caused extensive horizontal decay in the stem; such fungi were Ganoderma lipsiense on Tilia and Acer, Phellinus igniarius on Acer, Inonotus obliquus and Cerrena unicolor on Betula and Kretzschmaria deusta on Acer, Tilia and Betula. Typically, Rigidoporus populinus was frequently present in weak fork formations on Acer trees. Agaric fungi (Pholiota, Armillaria, Pleurotus and Hypholoma) were frequently recorded but were of minor importance from the point of view of tree breakage hazard.
Rupture of hepatic aneurysm complicating hereditary hemorrhagic telangiectasia (Osler–Weber–Rendu disease) for which hepatic arterial coil embolization was effective
Authors: Miyabe Katsuyuki , Akita Shinji , Kitajima Yasuhiro , Hirai Masaaki , Naitoh Itaru , Hayashi Kazuki , Okamoto Tetsu , Okayama Yasutaka , Gotoh Kazuo , Ohara Hirotaka , Joh Takashi , Yokoyama Yoshifumi , Itoh Makoto
Published: November 2007

A 74‐year‐old woman was transferred to our hospital for further examinations because of abdominal fullness and abnormal levels of serum liver/biliary enzyme persisting for 3 weeks. She had anemia and dilatation of many capillary vessels in her fingers, palms, and tongue in addition to reporting frequent incidences of nasal bleeding in herself and her family. Abdominal ultrasonography detected a cystic lesion in the right hepatic lobe, connected to a dilated tortuous hepatic artery. A low‐echoic hepatic phyma was also detected in the back of the cystic lesion. Abdominal computed tomography and magnetic resonance imaging indicated that the cystic lesion was an aneurysm and the low‐echoic phyma was a hematoma. Hepatic arteriography confirmed a hepatic aneurysm, tortuous dilatation of the hepatic artery, and the complication of an arteriovenous shunt in the liver. Taking all of these findings into consideration, this case was diagnosed as hereditary hemorrhagic telangiectasia (HTT) complicated by a hepatic aneurysm causing intrahepatic hematoma. To prevent re‐rupture of the aneurysm, we performed a hepatic arterial coil embolization. After therapy, no blood flow to the aneurysm was detected by ultrasonic color Doppler method and the hematoma gradually diminished. There have been no reports of a case in which hepatic arterial embolization was effective for HHT‐associated hepatic aneurysm causing intrahepatic hematoma. This very rare case provides important clinical information regarding abdominal vascular complications of HTT and a less invasive treatment for them.
Association of chronic hepatitis B virus infection with insulin resistance and hepatic steatosis
Authors: Wang Chia‐Chi , Hsu Ching‐Sheng , Liu Chun‐Jen , Kao Jia‐Horng , Chen Ding‐Shinn
Published: November 2007

Background and Aim:  Chronic viral infections such as human immunodeficiency virus and hepatitis C virus (HCV) may decrease tissue response to insulin, thereby causing insulin resistance. In addition, insulin resistance is associated with hepatic steatosis. However, whether these phenomena hold true for chronic hepatitis B virus (HBV) infection remains largely unknown. The present study therefore aimed to investigate the association of chronic HBV infection with insulin resistance and hepatic steatosis.

Methods:  A total of 507 subjects (243 men and 264 women; mean age 46.56 years) less than 60 years‐old attending a health examination center were enrolled in the study. All the subjects were negative for antibodies against HCV and consumed less than 140 g alcohol/week. Demographic, anthropometric, clinical, and laboratory data were obtained from each subject. Insulin resistance index was determined using homeostasis model assessment (HOMA‐IR). Hepatic steatosis was identified by ultrasound examination.

Results:  Of the 507 subjects, 50 (9.9%) were positive for hepatitis B surface antigen (HBsAg) and designated HBV carriers. All variables were comparable between HBV carriers and non‐HBV carriers, except that HBV carriers had significantly higher serum alanine aminotransferase and aspartate aminotransferase levels (P < 0.05). By multivariate linear regression, HBV carriers were not associated with insulin resistance. In addition, multivariate regression analyses showed that HBV carriers were not associated with the presence of ultrasonographic fatty liver.

Conclusions:  Chronic HBV infection seems not to be associated with insulin resistance or hepatic steatosis in HBV carriers.
Pharmacology and new perspectives of angiotensin II receptor blocker in prostate cancer treatment
Authors: Uemura Hiroji , Ishiguro Hitoshi , Kubota Yoshinobu
Published: November 2007

Abstract:  Although a low prevalence of cancer in hypertensive patients receiving angiotensin converting enzyme inhibitors has been reported, the molecular mechanisms have not been elucidated. It is known that angiotensin‐II (Ang‐II) plays a fundamental role not only as a vasoconstrictor in controlling blood pressure and electrolyte and fluid homeostasis, but also as a mitogenic factor through the Ang‐II type‐1 (AT1) receptor in cardiovascular cells. Interestingly, there is increasing evidence that the renin‐angiotensin system (RAS) is implicated in the development of various cancers. As we previously reported, AT1 receptor blockers (ARBs), a class of antihypertensive agent, have the potential to inhibit the growth of prostate cancer cells and tumors through the AT1 receptor. This review provides an insight into the key role of Ang‐II and the AT1 receptor, and the possibility of ARBs for molecular targeting of mitogenesis and angiogenesis in prostate cancer.