bluuebunny/crossref_metadata_2025 huggingface dataset:
Species delimitation and distribution in Aporometra (Crinoidea:Echinodermata): endemic Australian featherstars
Authors: Helgen Lauren E. , Rouse Greg W.
Published: June 2006

Aporometra Clark, 1938, which belongs to the monotypic Aporometridae, is a crinoid genus endemic to temperate Australian waters. It has been described as being ‘viviparous’ and is among the smallest of comatulids. The small size of specimens, and poor morphological justifications for specific diagnoses have created uncertainty over the number of species in the genus and their distributions. This study identified a suite of characters using data from scanning electron microscopy and mtDNA sequencing (CO1 and ND2) to assess the number of species of Aporometra. Specimens were obtained from museums and collected from Western Australia, South Australia, Victoria and New South Wales. Type material was also examined when possible. Phylogenetic hypotheses were generated using maximum parsimony-based analyses of the separate and combined datasets. The results support the monophyly of Aporometra and the presence of two species, Aporometra wilsoni (Bell, 1888) and Aporometra occidentalis A. H. Clark, 1938, along the southern Australian coast. The status of the third nominal species, Aporometra paedophora (H. L. Clark, 1909), remains to be resolved, but it may be a junior synonym of A. wilsoni. Morphological diagnoses are reviewed. Aporometra occidentalis was only found in Western Australia, while A. wilsoni was found from Western Australia to Victoria. Phylogeographic differentiation between the western and southern populations of A. wilsoni is briefly discussed.
Ionizing radiation induces caspase-dependent but Chk2- and p53-independent cell death in
Drosophila melanogaster
Authors: Wichmann Anita , Jaklevic Burnley , Su Tin Tin
Published: June 2006

Ionizing radiation (IR) can induce apoptosis via p53, which is the most commonly mutated gene in human cancers. Loss of p53, however, can render cancer cells refractory to therapeutic effects of IR. Alternate p53-independent pathways exist but are not as well understood as p53-dependent apoptosis. Studies of how IR induces p53-independent cell death could benefit from the existence of a genetically tractable model. In
Drosophila melanogaster
, IR induces apoptosis in the imaginal discs of larvae, typically assayed at 4–6 hr after exposure to a LD
50
dose. In mutants of
Drosophila
Chk2 or p53 homologs, apoptosis is severely diminished in these assays, leading to the widely held belief that IR-induced apoptosis depends on these genes in
Drosophila
. In this article, we show that IR-induced apoptosis still occurs in the imaginal discs of
chk2
and
p53
mutant larvae, albeit with a delay. We demonstrate that this phenomenon is a true apoptotic response because it requires caspase activity and the chromosomal locus that encodes the pro-apoptotic genes
reaper
,
hid
, and
grim
. We also show that Chk2- and p53-independent apoptosis is IR dose-dependent and is therefore probably triggered by a DNA damage signal. We conclude that
Drosophila
has Chk2- and p53-independent pathways to activate caspases and induce apoptosis in response to IR. This work establishes
Drosophila
as a model for p53-independent apoptosis, which is of potential therapeutic importance for inducing cell death in p53-deficient cancer cells.
Discovery of a small-molecule HIV-1 integrase inhibitor-binding site
Authors: Al-Mawsawi Laith Q. , Fikkert Valery , Dayam Raveendra , Witvrouw Myriam , Burke Terrence R. , Borchers Christoph H. , Neamati Nouri
Published: June 2006

Herein, we report the identification of a unique HIV-1 integrase (IN) inhibitor-binding site using photoaffinity labeling and mass spectrometric analysis. We chemically incorporated a photo-activatable benzophenone moiety into a series of coumarin-containing IN inhibitors. A representative of this series was covalently photo-crosslinked with the IN core domain and subjected to HPLC purification. Fractions were subsequently analyzed by using MALDI-MS and electrospray ionization (ESI)-MS to identify photo-crosslinked products. In this fashion, a single binding site for an inhibitor located within the tryptic peptide
128
AACWWAGIK
136
was identified. Site-directed mutagenesis followed by
in vitro
inhibition assays resulted in the identification of two specific amino acid residues, C130 and W132, in which substitutions resulted in a marked resistance to the IN inhibitors. Docking studies suggested a specific disruption in functional oligomeric IN complex formation. The combined approach of photo-affinity labeling/MS analysis with site-directed mutagenesis/molecular modeling is a powerful approach for elucidating inhibitor-binding sites of proteins at the atomic level. This approach is especially important for the study of proteins that are not amenable to traditional x-ray crystallography and NMR techniques. This type of structural information can help illuminate processes of inhibitor resistance and thereby facilitate the design of more potent second-generation inhibitors.
Nociceptin/orphanin FQ presynaptically decreases GABAergic transmission and blocks the ethanol-induced increase of GABA release in central amygdala
Authors: Roberto Marisa , Siggins George R.
Published: June 2006

Behavioral studies show that the GABAergic system in the central amygdala (CeA) nucleus has a complex role in the reinforcing effects effects of ethanol and the anxiogenic response to ethanol withdrawal. Opioid peptides and nociceptin/orphanin FQ (nociceptin) within the CeA are implicated also in regulating voluntary ethanol consumption and ethanol relapse. Recently, we reported that basal GABAergic transmission was increased in ethanol-dependent rats, and that acute ethanol increases GABA
A
receptor-mediated inhibitory postsynaptic currents (IPSCs) in CeA neurons from both naïve and ethanol-dependent rats to the same extent, suggesting lack of tolerance for the acute effect of ethanol. Here, we investigated the effect of nociceptin on IPSCs in CeA neurons and its interaction with ethanol effects on these GABA synapses. We found that nociceptin moderately decreased IPSC amplitudes, acting mostly presynaptically as it increased paired-pulse facilitation ratio of IPSCs and decreased miniature IPSC frequencies (but not amplitudes). Nociceptin also prevented the ethanol-induced augmentation of IPSCs in CeA of naïve rats. Interestingly, in CeA of ethanol-dependent rats, the nociceptin-induced inhibition of IPSCs was increased, indicating an enhanced sensitivity to nociceptin. Nociceptin also blocked the ethanol-induced augmentation of IPSCs in ethanol-dependent rats. Our data suggest that nociceptin has a role in regulating the GABAergic system and opposing the effect elicited by ethanol. Thus, nociceptin may represent a therapeutic target for alleviating alcohol dependence.
Hippocampal disconnection contributes to memory dysfunction in individuals at risk for Alzheimer’s disease
Authors: Stoub Travis R. , deToledo-Morrell Leyla , Stebbins Glenn T. , Leurgans Sue , Bennett David A. , Shah Raj C.
Published: June 2006

The concept of amnestic mild cognitive impairment (MCI) describes older people who show a decline predominantly in memory function, but who do not meet criteria for dementia. Because such individuals are at high risk for developing Alzheimer’s disease, they are of great interest for understanding the prodromal stages of the disease process. The mechanism underlying memory dysfunction in people with MCI is not fully understood. The present study uses quantitative, high-resolution structural MRI techniques to investigate,
in vivo
, the anatomical substrate of memory dysfunction associated with MCI. Changes in brain structures were assessed with two imaging techniques: (
i
) whole-brain, voxel-based morphometry to determine regions of reduced white matter volume and (
ii
) sensitive volumetric segmentation of the entorhinal cortex and hippocampus, gray matter regions that are critically important for memory function. In participants with amnestic MCI, compared with age-matched controls, results showed a significant decrease in white matter volume in the region of the parahippocampal gyrus that includes the perforant path. There was also significant atrophy in both the entorhinal cortex and the hippocampus. Regression models demonstrated that both hippocampal volume and parahippocampal white matter volume were significant predictors of declarative memory performance. These results suggest that, in addition to hippocampal atrophy, disruption of parahippocampal white matter fibers contributes to memory decline in elderly individuals with MCI by partially disconnecting the hippocampus from incoming sensory information.
Low-dimensional, free-energy landscapes of protein-folding reactions by nonlinear dimensionality reduction
Authors: Das Payel , Moll Mark , Stamati Hernán , Kavraki Lydia E. , Clementi Cecilia
Published: June 2006

The definition of reaction coordinates for the characterization of a protein-folding reaction has long been a controversial issue, even for the “simple” case in which one single free-energy barrier separates the folded and unfolded ensemble. We propose a general approach to this problem to obtain a few collective coordinates by using nonlinear dimensionality reduction. We validate the usefulness of this method by characterizing the folding landscape associated with a coarse-grained protein model of src homology 3 as sampled by molecular dynamics simulations. The folding free-energy landscape projected on the few relevant coordinates emerging from the dimensionality reduction can correctly identify the transition-state ensemble of the reaction. The first embedding dimension efficiently captures the evolution of the folding process along the main folding route. These results clearly show that the proposed method can efficiently find a low-dimensional representation of a complex process such as protein folding.
Pegasoferae, an unexpected mammalian clade revealed by tracking ancient retroposon insertions
Authors: Nishihara Hidenori , Hasegawa Masami , Okada Norihiro
Published: June 2006

Despite the recent large-scale efforts dedicated to comprehensive phylogenetic analyses using mitochondrial and nuclear DNA sequences, several relationships among mammalian orders remain controversial. Here, we present an extensive application of retroposon (L1) insertion analysis to the phylogenetic relationships among almost all mammalian orders. In addition to demonstrating the validity of Glires, Euarchontoglires, Laurasiatheria, and Boreoeutheria, we demonstrate an interordinal clade that links Chiroptera, Carnivora, and Perissodactyla within Laurasiatheria. Re-examination of a large DNA sequence data set yielded results consistent with our conclusion. We propose a superordinal name “Pegasoferae” for this clade of Chiroptera + Perissodactyla + Carnivora + Pholidota. The presence of a single incongruent L1 locus generates a tree in which the group of Carnivora + Perissodactyla associates with Cetartiodactyla but not with Chiroptera. This result suggests that incomplete lineage sorting of an ancestral dimorphism occurred with regard to the presence or absence of retroposon alleles in a common ancestor of Scrotifera (Pegasoferae + Cetartiodactyla), which was followed by rapid divergence into the extant orders over an evolutionarily short period. Accordingly, Euungulata (Cetartiodactyla + Perissodactyla) and Fereuungulata (Carnivora + Pholidota + Perissodactyla + Cetartiodactyla) cannot be validated as natural groups. The interordinal mammalian relationships presented here provide a cornerstone for future studies in the reconstruction of mammalian classifications, including extinct species, on evolution of large genomic sequences and structure, and in developmental analysis of morphological diversification.
Formation of two methylenedioxy bridges by a
Sesamum
CYP81Q protein yielding a furofuran lignan, (+)-sesamin
Authors: Ono Eiichiro , Nakai Masaaki , Fukui Yuko , Tomimori Namino , Fukuchi-Mizutani Masako , Saito Masayuki , Satake Honoo , Tanaka Takaharu , Katsuta Masumi , Umezawa Toshiaki , Tanaka Yoshikazu
Published: June 2006

(+)-Sesamin, a furofuran class lignan, is widespread in vascular plants and represented by
Sesamum
spp. (+)-Sesamin has been of rapidly growing interest because of its beneficial biological effects in mammals, but its biosynthesis and physiological roles in plants remain to be clarified. It is speculated to be synthesized from (+)-pinoresinol by means of (+)-piperitol by formation of two methylenedioxy bridges mediated by two distinct
Sesamum indicum
cytochrome P450 (SiP450) proteins. Here, we report an SiP450, CYP81Q1, that alone catalyzes (+)-sesamin biosynthesis from (+)-pinoresinol by means of (+)-piperitol by forming two methylenedioxy bridges. The CYP81Q1 gene expression profile was temporally consistent with the accumulation pattern of (+)-sesamin during seed development. The CYP81Q1-GFP chimera protein was colocalized with an endoplasmic reticulum (ER)-targeting chimera protein, indicating that (+)-sesamin biosynthesis occurs on the ER cytoplasmic surface. Moreover, we isolated two CYP81Q1 homologs from other
Sesamum
spp.
Sesamum radiatum
CYP81Q2 showed dual (+)-piperitol/(+)-sesamin synthetic activity. CYP81Q2, as well as CYP81Q1, therefore, corresponds to a (+)-piperitol/(+)-sesamin synthase in lignan biosynthesis. In contrast,
Sesamum alatum
CYP81Q3 showed no activity, in accord with (+)-sesamin being deficient in
S. alatum
. Our findings not only provide insight into lignan biosynthesis but also unravel a unique mode of cytochrome P450 action.
Involvement of human left dorsolateral prefrontal cortex in perceptual decision making is independent of response modality
Authors: Heekeren H. R. , Marrett S. , Ruff D. A. , Bandettini P. A. , Ungerleider L. G.
Published: June 2006

Perceptual decision making typically entails the processing of sensory signals, the formation of a decision, and the planning and execution of a motor response. Although recent studies in monkeys and humans have revealed possible neural mechanisms for perceptual decision making, much less is known about how the decision is subsequently transformed into a motor action and whether or not the decision is represented at an abstract level, i.e., independently of the specific motor response. To address this issue, we used functional MRI to monitor changes in brain activity while human subjects discriminated the direction of motion in random-dot visual stimuli that varied in coherence and responded with either button presses or saccadic eye movements. We hypothesized that areas representing decision variables should respond more to high- than to low-coherence stimuli independent of the motor system used to express a decision. Four areas were found that fulfilled this condition: left posterior dorsolateral prefrontal cortex (DLPFC), left posterior cingulate cortex, left inferior parietal lobule, and left fusifom/parahippocampal gyrus. We previously found that, when subjects made categorical decisions about degraded face and house stimuli, left posterior DLPFC showed a greater response to high- relative to low-coherence stimuli. Furthermore, the left posterior DLPFC appears to perform a comparison of signals from sensory processing areas during perceptual decision making. These data suggest that the involvement of left posterior DLPFC in perceptual decision making transcends both task and response specificity, thereby enabling a flexible link among sensory evidence, decision, and action.
Visualization of a group II intron in the 23S rRNA of a stable ribosome
Authors: Slagter-Jäger Jacoba G. , Allen Gregory S. , Smith Dorie , Hahn Ingrid A. , Frank Joachim , Belfort Marlene
Published: June 2006

Thousands of introns have been localized to rRNA genes throughout the three domains of life. The consequences of the presence of either a spliced or an unspliced intron in a rRNA for ribosome assembly and packaging are largely unknown. To help address these questions, and to begin an intron imaging study, we selected a member of the self-splicing group II intron family, which is hypothesized to be the progenitor not only of spliceosomal introns but also of non-LTR retrotransposons. We cloned the self-splicing group II Ll.LtrB intron from
Lactococcus lactis
into
L. lactis
23S rRNA. The 2,492-nt Ll.LtrB intron comprises a catalytic core and an ORF, which encodes a protein, LtrA. LtrA forms a ribonucleoprotein (RNP) complex with the intron RNA to mediate splicing and mobility. The chimeric 23S–intron RNA was shown to be splicing proficient in its native host in the presence of LtrA. Furthermore, a low-resolution cryo-EM reconstruction of the
L. lactis
ribosome fused to the intron–LtrA RNP of a splicing-defective Ll.LtrB intron was obtained. The image revealed the intron as a large, well defined structure. The activity and structural integrity of the intron indicate not only that it can coexist with the ribosome but also that its presence permits the assembly of a stable ribosome. Additionally, we view our results as a proof of principle that ribosome chimeras may be generally useful for studying a wide variety of structured RNAs and RNP complexes that are not amenable to NMR, crystallographic, or single-particle cryo-EM methodologies.
Traditional Toxicity Documentation of Chinese Materia Medica—An Overview
Authors: Leung Albert Y.
Published: June 2006

Documentation of Chinese materia medica (CMM) dates back to around 1,100 BC when only dozens of drugs were first described. By the end of the 16th century, the number of drugs documented had reached close to 1,900. And by the end of the last century, published records of CMM have reached 12,800 drugs. The recorded traditional information includes toxicities, incompatibilities, cautions, precautions and contraindications. Thus, contrary to a general misconception, toxicity data on Chinese herbs exist and are not meager. If consulted properly before embarking on a study of CMM, it will save researchers much time and efforts and the frustration of not obtaining consistent or expected results. The history of documentation is reviewed with examples of major classic and contemporary works highlighting and emphasizing the manner in which CMM toxicities have traditionally been documented through clinical experience as opposed to most modern toxicity data that are based on animal experimentation.
Criminal justice policies: Trends and their impact on prison health
Authors: Christie Nils
Published: June 2006

The general theme for this conference is ‘prisons and public health’. Therefore, let me begin with an obvious, but often ignored point, by saying: the best tool for improved prison health is to reduce the prison population. Such a measure would also reduce crime, but I ignore that point here, and concentrate on health. Punishment is intended delivery of pain. Prisons represent a major instrument for the delivery of that pain. Those working in the prisons do much to alleviate pain, as beautifully illustrated by Alison Liebling (2004) in her book Prisons and their moral performance. In individual cases, prisoners might also profit from spending some time in prison.2 None the less, prisons are close relatives to capital punishment. Not the whole life, but parts, of a person’s life is taken. I have never been able to forget an elderly man I once met in the major prison in Oslo. ‘Spring is the worst’, he said. ‘Not because of the explosions in green pleasures outside, but because it was in spring that I was imprisoned. Each new spring is a reminder that one more year is lost. There are not so many left.’
Quality of life following emergency liver transplantation for acute liver failure
Authors: Sargent Suzanne , Wainwright Steven P.
Published: June 2006

Introduction. Liver transplantation is an accepted and successful therapy for both acute and chronic liver diseases (CLDs), with good survival outcomes. Whilst the study of health‐related quality of life (HRQoL) post transplantation for CLDs have been well documented, there is little data measuring HRQoL following liver transplantation for acute liver failure (ALF) patients. Patients and methods. Data were collected using between‐method triangulation; however, only the quantitative element of the study is reported here. Measuring eight health domains, we distributed the short form 36 (SF‐36) questionnaire by post to 96 acute and chronic transplant recipients. Differences between the groups were measured using both parametric and non‐parametric t‐tests. Results. Overall, the patients showed a satisfactory HRQoL; there were no differences between either acute or chronic transplant groups in seven of the eight domains of quality of life. Among the patients transplanted for ALF, there were no differences in HRQoL between patients transplanted for paracetamol hepatotoxicity compared with other indications, and no variations in HRQoL related to recipient gender, employment or length of survival post transplantation. When compared with the UK SF‐36 normal values to the ALF transplant recipients, there was a significantly lower physical functioning and role emotional scores. Conclusion. Regardless of aetiology, most of recipients transplanted for ALF have a HRQoL comparable with chronic transplant recipients.
A critical discourse analysis of provision of end‐of‐life care in key UK critical care documents
Authors: Pattison Natalie
Published: June 2006

This article highlights certain practical and professional difficulties in providing end‐of‐life (EOL) care for patients in critical care units and explores discourses arising from guidelines for critical care services. Background : A significant number of patients die in critical care after decisions to withdraw or withhold treatment. Guidelines for provision of critical care suggest, wherever possible, moving patients out of critical care at the EOL. This may not necessarily be conducive to a ‘good death’ for patients or their loved ones. There is a moral responsibility for both nurses and doctors to ensure that decision‐making around EOL issues is sensitively implemented, that decisions about care includes families, patients when able, nurses and doctors, and that good EOL care is provided. Methods : A critical discourse analysis (CDA) of four key UK critical care documents published since 1996. Findings and recommendations : The key documents give little clear guidance about how to provide EOL care in critical care. Discourses include the power dynamic in critical care between professions, families and patients, and how this impacts on provision of EOL care. Difficulties encountered include dilemmas at discharge and paternalism in decision‐making. The technological environment can act as a barrier to good EOL care, and critical care nurses are at risk of assuming the dominant medical model of care. Nurses, however, are in a prime position to ensure that decision‐making is an inclusive process, patient needs are paramount, the practical aspects of withdrawal lead to a smooth transition in goals of care and that comfort measures are implemented.
Does the efficacy of supplemental oxygen for the prevention of postoperative nausea and vomiting depend on the measured outcome, observational period or site of surgery?
Authors: Turan A. , Apfel C. C. , Kumpch M. , Danzeisen O. , Eberhart L. H. J. , Forst H. , Heringhaus C. , Isselhorst C. , Trenkler S. , Trick M. , Vedder I. , Kerger H.
Published: June 2006

High intra‐operative oxygen concentration reportedly reduces postoperative nausea and vomiting (PONV), but recent data are conflicting. Therefore, we tested whether the effectiveness of supplemental oxygen depends on the endpoint (nausea vs. vomiting), observation interval (early vs. late) or surgical field (abdominal vs. non‐abdominal). We randomly assigned 560 adult patients undergoing various elective procedures with a PONV risk of at least 40% to intra‐operative 80% (supplemental) or 30% oxygen (control). Potential confounding factors were similar between groups. Incidences of nausea were similar in the groups during early (12% (supplemental) vs. 10% (control), p = 0.43) and late intervals, 26%vs. 20%, p = 0.09, as were the incidences of vomiting (early: 2%vs. 3%, p = 0.40; late: 8%vs. 9%, p = 0.75). Supplemental oxygen was no more effective at reducing PONV in abdominal (40%vs. 31%, p = 0.37) than in non‐abdominal surgery (25%vs. 21%, p = 0.368). Thus, supplemental oxygen was unable to reduce PONV independent of the endpoint, observational period or site of surgery.
Proteasome inhibition as novel treatment strategy in leukaemia
Authors: Vink J. , Cloos J. , Kaspers G. J. L.
Published: June 2006

Following its success in multiple myeloma (MM), proteasome inhibition has become a topic of interest as novel treatment strategy of cancer. By simultaneously affecting multiple pathways in the cancer cell, such as deregulation of the programmed degradation of many cellular proteins, proteasome inhibition causes rapid apoptosis of these cells. Both in rapidly proliferating leukaemic cell lines and in primary leukaemic cells isolated from patients, proteasome inhibition results in antileukaemic activity. The normal counterparts of these cells are much more resistant to proteasome inhibitors (PI), thereby resulting in a favourable therapeutic index. Importantly, while leukaemic stem cells are sensitive to proteasome inhibition, normal haematopoietic stem cells are still viable after drug exposure. Nowadays, many PIs are being identified; bortezomib is the most well known since obtaining Food and Drug Administration approval for clinical use in MM. This review summarises the biological and clinical aspects of proteasome inhibition and discusses the potential role of these inhibitors in the treatment of leukaemia.
Manipulation of prothrombin concentration improves response to high‐dose factor VIIa in a cell‐based model of haemophilia
Authors: Allen Geoffrey A. , Hoffman Maureane , Roberts Harold R. , Monroe Dougald M.
Published: June 2006

Clinical reports suggest that treatment regimens employing both activated prothrombin complex concentrates (aPCCs) and recombinant activated factor VII (rFVIIa) may control the bleeding in patients with haemophilia who fail to respond to either agent alone. We hypothesised that increased concentrations of prothrombin, as may be observed after the infusion of aPCCs, favourably influence parameters of thrombin generation in haemophilia treated with high‐dose rFVIIa. We examined the effect of varied prothrombin and rFVIIa concentrations on thrombin generation in a model of haemophilia. At all concentrations of rFVIIa, increased prothrombin concentrations led to increases in the peak and rate of thrombin generation. In assays with the highest concentrations of prothrombin and rFVIIa, peak thrombin actually equalled that measured in the model of normal haemostasis. The significant impact of prothrombin concentration on the effect of rFVIIa in vitro may explain the improved haemostasis reported with concurrent use of aPCCs and rFVIIa. These results imply that persons with plasma prothrombin levels at either end of the ‘normal’ range could have significantly different responses to similar rFVIIa doses. Furthermore, these results suggest that increasing plasma prothrombin concentration prior to rFVIIa administration may offer advantages over the use of rFVIIa alone in the treatment of haemophilic bleeding.
Costimulation of naive human CD4+ T cells through intercellular adhesion molecule‐1 promotes differentiation to a memory phenotype that is not strictly the result of multiple rounds of cell division
Authors: Kohlmeier Jacob E. , Chan Marcia A. , Benedict Stephen H.
Published: June 2006

The process by which naive T cells become activated, differentiate into effector cells and ultimately generate long‐lived memory cells is dependent upon a number of factors, including the costimulatory signals received by the T cell. To best understand the multiple events involved, it is important to understand the potential contributions by individual signalling proteins using both in vitro and in vivo studies. Here, the potential for costimulation through intercellular adhesion molecule‐1 (ICAM‐1; CD54), resident on the surface of naive human T cells, to influence differentiation was investigated. Costimulation of naive T cells through ICAM‐1 resulted in expansive cell division, high interleukin‐2 production, and protection from apoptosis. Prolonged culture led to outgrowth of a subpopulation of cells with a highly differentiated CD45RA– CD11ahi CD27– phenotype. In this respect, costimulation through ICAM‐1 was similar to costimulation through CD28 and different from costimulation through leucocyte function‐associated antigen‐1. The CD45RA– CD11ahi CD27– cells responded to suboptimal stimulation through the T‐cell receptor alone with a more robust proliferative response compared with naive cells from the same subject. These cells also secreted higher levels of T helper type 1 cytokines in response to lower levels of stimulation than their naive counterparts. The surface phenotype and more sensitive response characteristics suggest the creation of a memory T‐cell subpopulation as a result of costimulation through ICAM‐1. Finally, generation of this memory population was the result of specific costimulatory signals, and not merely because of a high number of cell divisions. These data reveal a new role for resident ICAM‐1 to influence the differentiation of naive T cells.
Noninvasive ratio indexes to evaluate fibrosis staging in chronic hepatitis C: role of platelet count/spleen diameter ratio index.
Authors: TESTA R. , TESTA E. , GIANNINI E. , BORRO P. , MILAZZO S. , ISOLA L. , CEPPA P. , LANTIERI P. B. , RISSO D.
Published: June 2006

Objectives.  Noninvasive evaluation of fibrosis is an on‐going effort in the management of chronic hepatitis C. This study was planned to noninvasively evaluate fibrosis staging.

Design.  We evaluated the biochemical, functional [aminopyrine breath test (ABT)] and ultrasonographic variables of 75 chronic hepatitis C patients.

Results.  Clinical [body mass index (BMI)], biochemical [aspartate aminotransferase (AST), alanine aminotransferase (ALT) and platelets (PLT)] and ratio indexes, together with the ABT, showed a higher relationship with fibrosis: initial (score ≤ 2) versus evident (score > 2) fibrosis: BMI (24 ± 2 vs. 26 ± 2, P = 0.0007), AST (56 ± 36 vs. 88 ± 65, P = 0.0159), ALT (92 ± 54 vs. 139 ± 108, P = 0.0290), PLT (220 ± 64 vs. 173 ± 61, P = 0.0007), PLT/spleen diameter ratio (PLT/SPD) (2133 ± 786 vs. 1540 ± 681, P = 0.0003), AST/platelet count ratio index (APRI) (0.80 ± 0.87 vs. 1.51 ± 1.47, P = 0.0010), ABT%d/h30 min (10.8 ± 4.5 vs. 7.6 ± 3.8, P = 0.0007), ABT%d/cum120 min (8.9 ± 3.3 vs. 6.5 ± 3.1, P = 0.0007). Considering the differences between fibrosis score 2 and 3 patients, BMI, ABT and PLT/SPD ratio proved to be statistically significant. Multivariate stepwise analysis (with and without BMI) identified two models for distinguishing between initial and evident fibrosis: Model 1: −0.569 +(BMI × 0.107) + (APRI × 0.169)−(PLT/SPD × 0.304), and Model 2: 2.376 + (APRI × 0.152)−(ABTd/h30 × 0.043)−(PLT/SPD × 0.249). These models showed concordance in identifying or ruling out evident fibrosis in 76% and 78.7% of the patients respectively. The PLT/SPD ratio also showed 78.7% concordance with the histological score.

Conclusion.  These results suggest that noninvasive evaluation of fibrosis in chronic hepatitis C may be considered an effective tool thanks to the use of an inexpensive, reproducible ratio index.
Migration and recovery of the genetic diversity during the increasing density phase in cyclic vole populations
Authors: BERTHIER K. , CHARBONNEL N. , GALAN M. , CHAVAL Y. , COSSON J.‐F.
Published: June 2006

In cyclic populations, high genetic diversity is currently reported despite the periodic low numbers experienced by the populations during the low phases. Here, we report spatio‐temporal monitoring at a very fine scale of cyclic populations of the fossorial water vole (Arvicola terrestris) during the increasing density phase. This phase marks the transition from a patchy structure (demes) during low density to a continuous population in high density. We found that the genetic diversity was effectively high but also that it displayed a local increase within demes over the increasing phase. The genetic diversity remained relatively constant when considering all demes together. The increase in vole abundance was also correlated with a decrease of genetic differentiation among demes. Such results suggest that at the end of the low phase, demes are affected by genetic drift as the result of being small and geographically isolated. This leads to a loss of local genetic diversity and a spatial differentiation among demes. This situation is counterbalanced during the increasing phase by the spatial expansion of demes and the increase of the effective migration among differentiated demes. We provide evidences that in cyclic populations of the fossorial water voles, the relative influence of drift operating during low density populations and migration occurring principally while population size increases interacts closely to maintain high genetic diversity.
Evidence for Golgi‐independent transport from the early secretory pathway to the plastid in malaria parasites
Authors: Tonkin Christopher J. , Struck Nicole S. , Mullin Kylie A. , Stimmler Luciana M. , McFadden Geoffrey I.
Published: June 2006

The malaria parasite Plasmodium falciparum harbours a relict plastid (termed the apicoplast) that has evolved by secondary endosymbiosis. The apicoplast is surrounded by four membranes, the outermost of which is believed to be part of the endomembrane system. Nuclear‐encoded apicoplast proteins have a two‐part N‐terminal extension that is necessary and sufficient for translocation across these four membranes. The first domain of this N‐terminal extension resembles a classical signal peptide and mediates translocation into the secretory pathway, whereas the second domain is homologous to plant chloroplast transit peptides and is required for the remaining steps of apicoplast targeting. We explored the initial, secretory pathway component of this targeting process using green fluorescent reporter protein constructs with modified leaders. We exchanged the apicoplast signal peptide with signal peptides from other secretory proteins and observed correct targeting, demonstrating that apicoplast targeting is initiated at the general secretory pathway of P. falciparum. Furthermore, we demonstrate by immunofluorescent labelling that the apicoplast resides on a small extension of the endoplasmic reticulum (ER) that is separate from the cis‐Golgi. To define the position of the apicoplast in the endomembrane pathway in relation to the Golgi we tracked apicoplast protein targeting in the presence of the secretory inhibitor Brefeldin A (BFA), which blocks traffic between the ER and Golgi. We observe apicoplast targeting in the presence of BFA despite clear perturbation of ER to Golgi traffic by the inhibitor, which suggests that the apicoplast resides upstream of the cis‐Golgi in the parasite's endomembrane system. The addition of an ER retrieval signal (SDEL) – a sequence recognized by the cis‐Golgi protein ERD2 – to the C‐terminus of an apicoplast‐targeted protein did not markedly affect apicoplast targeting, further demonstrating that the apicoplast is upstream of the Golgi. Apicoplast transit peptides are thus dominant over an ER retention signal. However, when the transit peptide is rendered non‐functional (by two point mutations or by complete deletion) SDEL‐specific ER retrieval takes over, and the fusion protein is localized to the ER. We speculate either that the apicoplast in P. falciparum resides within the ER directly in the path of the general secretory pathway, or that vesicular trafficking to the apicoplast directly exits the ER.
An evolutionarily conserved translation initiation mechanism regulates nuclear or mitochondrial targeting of DNA ligase 1 in Arabidopsis thaliana
Authors: Sunderland Paul A. , West Christopher E. , Waterworth Wanda M. , Bray Clifford M.
Published: June 2006

The Arabidopsis DNA ligase 1 gene (AtLIG1) is indispensable for cell viability. AtLIG1 expresses one major and two minor mRNA transcripts differing only in the length of the 5′ untranslated leader sequences preceding a common ORF. Control of AtLIG1 isoform production and intracellular targeting depends upon mechanisms controlling the choice of translation initiation site within the AtLIG1 ORF. Confocal laser scanning microscopy of green fluorescent protein‐tagged AtLIG1 isoforms expressed in Arabidopsis revealed that translation of AtLIG1 mRNA transcripts from the first in‐frame start codon produces an AtLIG1 isoform that is targeted exclusively to the mitochondria. Translation initiation from the second in‐frame start codon produces an AtLIG1 isoform targeted only to the nucleus. There is no evidence for AtLIG1–GFP being targeted to chloroplasts. The mitochondrial AtLIG1 isoform possesses both an N‐terminal mitochondrial‐targeting signal and an internal bipartite nuclear localization signal (NLS) yet is targeted only to mitochondria, demonstrating a hierarchical dominance of the mitochondrial presequence over the NLS. The length of the 5′‐UTR and more significantly the nucleotide context around alternative start codons in the AtLIG1 transcripts affect translation initiation to ensure a balanced synthesis of both nuclear and mitochondrial AtLIG1 isoforms, probably via a context‐dependent leaky ribosome scanning mechanism.
Cooperative Goals, Leader People and Productivity Values: Their Contribution to Top Management Teams in China*
Authors: Chen Guoquan , Tjosvold Dean , Liu Chunhong
Published: June 2006

abstract  This study proposes that when top management team members are convinced that their leader is committed to people and productivity, they conclude that their leader is effective and contribute to making their organization innovative. Cooperative goals among top management team members may be credible evidence that their leader has people and production values. Executives from over 100 organizations in China completed measures of their cooperative, competitive, and independent goals, their leader's people and production values, and their leader's effectiveness. CEOs from these firms rated their organization's innovativeness. Structural equation analysis suggested that cooperative goals among top management teams convince them that their leader values people and production and that these values in turn result in leader effectiveness and organizational innovation. Results, coupled with previous research, were interpreted as suggesting that cooperative goals and leader people and production values are foundations for leader and top management team effectiveness in China.
Board Characteristics and Involvement in Strategic Decision Making: Evidence from Swiss Companies*
Authors: Ruigrok Winfried , Peck Simon I. , Keller Hansueli
Published: June 2006

abstract Boards of directors have a number of roles. The board's monitoring function has been the subject of much work. Less examined is the role that the board has in setting company strategy. This paper uses agency and network perspectives in developing and testing the relationship between board characteristics and involvement in strategic decision making. Using primary and secondary data, our results suggest that the level of board involvement in strategic decision making is related to a number of governance variables. We demonstrate that involvement is generally lower where boards are highly interlocked. We also show that certain types of board interlocks – namely horizontal (same industry) and those involving direct links with the banking sector – are particularly associated with this negative effect. There is weaker evidence that board strategic involvement is lower where the roles of company chief executive and chair are combined. We find no evidence that factors such as board size, or the percentage of outside directors per se are related to board involvement in strategic decision making. In doing so, this paper adds to the growing literature synthesizing the structural features and processes of boards.
Quantitative Sensory Testing in Cluster Headache: Increased Sensory Thresholds
Authors: Ladda J , Straube A , Förderreuther S , Krause P , Eggert T
Published: June 2006

To determine if recently reported changes in sensory thresholds during migraine attacks can also be seen in cluster headache (CH), we performed quantitative sensory testing (QST) in 10 healthy subjects and in 16 patients with CH. Eight of the patients had an episodic CH and the other eight a chronic CH. The tests were performed on the right and left cheeks and on the right and left side of the back of the hands to determine the subjects' perception and pain thresholds for thermal (use of a thermode) and mechanical (vibration, pressure pain thresholds, pin prick, von Frey hairs) stimuli. Six patients were examined in the attack-free period. Three were also willing to repeat the tests a second time during an acute headache attack, which was elicited with nitroglycerin. The healthy subjects performed the experiments in the morning and evening of the same day to determine if sensory thresholds are independent of the time of day. If they were, this would allow estimation of the influence of the endogenous cortisone concentration on these thresholds. The control group showed no influence of the time of day on the thresholds. There was a significant difference in pain sensitivity between the back of the hands and the cheeks ( P < 0.05): higher thresholds were found on the back of the hands. The thresholds generally exhibited little intersubject variability, indicating that QST is a reliable method. There was also a significant difference between the test areas in the patient group ( P < 0.001): the cheeks were also more sensitive than the back of the hands. In comparison with reference data of healthy volunteers, the detection thresholds were increased in the patients on both test areas. These were statistically significant for warmth, thermal sensory limen (TSL), heat and pressure on the back of the hands ( P < 0.04) and for the warmth and TSL thresholds on the cheeks ( P < 0.05). There were no differences in the thresholds regardless of whether the patients were examined in or outside of a cluster bout. Furthermore, we found no cutaneous allodynia in the three patients tested during an attack. The increased sensory thresholds on the cheeks as well as on the back of the hands are in agreement with an increased activation of the patients' antinociceptive system. The seasonal variation and the temporal regularity of single attacks as well as the findings in imaging studies indicate that the hypothalamus is involved in the pathophysiology of CH. In view of the strong connectivity between the hypothalamus and areas involved in the antinociceptive system in the brainstem, we hypothesize that this connection is the reason for the increased sensory thresholds in CH patients found in our study.
Sampling and analysis of geothermal fluids
Authors: ARNÓRSSON S. , BJARNASON J. Ö. , GIROUD N. , GUNNARSSON I. , STEFÁNSSON A.
Published: June 2006

Sampling of geothermal fluids presents some problems not encountered when sampling surface and nonthermal ground waters. Specific collection techniques are required to obtain representative samples because of the elevated temperature and boiling of these fluids, the effect of exposing them to the atmosphere and cooling of the samples. Sample treatment during collection depends on the analytical method to be used. When sampling wet‐steam wells, both the liquid and the vapour fractions should be collected at the same fluid separation pressure. When sampling fumarole steam, maximum information is obtained if the total discharge is collected into a single container without separating the gas and the steam condensate fractions. Silica polymerization affects the solution pH. The only way to obtain reliable pH measurement of a water sample supersaturated with respect to amorphous silica is to measure it on site, before the onset of polymerization. This paper provides an outline of the geothermal sampling techniques and analytical methods currently in use in Iceland. Sampling of hot‐water and wet‐steam wells is described, as is sampling of hot springs, fumaroles and gas bubbling through hot‐spring waters. Detailed procedures are given for the analysis of total carbonate carbon and total sulphide sulphur in geothermal water and steam condensate samples.
Habitat use of the endangered butterflyEuphydryas maturnaand forestry in Central Europe
Authors: Freese A. , Benes J. , Bolz R. , Cizek O. , Dolek M. , Geyer A. , Gros P. , Konvicka M. , Liegl A. , Stettmer C.
Published: June 2006

The knowledge of ecological requirements of declining butterflies of European woodlands remains limited, which hinders conservation management of their localities. This also applies for continentally threatened scarce fritillaryEuphydryas maturna. On the basis of the largest data set on its habitat use ever collected in Central Europe, we analyse habitat requirements of its populations in Austria (A), the Czech Republic (Cz) and Germany (D). All studied populations inhabit open‐canopy sites within woodlands, but larval survival decreases under full sun and preferred sites are relatively humid and sheltered. Nests of pre‐hibernation larvae occur at terminal branches ofFraxinus excelsior, 1.5–3 m above the ground. Pre‐hibernation mortality reaches 70% (Cz, D). Another limiting factor is quality of woodland vegetation: post‐hibernation larvae consume a wide range of herbs and shrubs, and adult distribution is linked to nectar availability. The butterfly thus depends on highly heterogeneous early successional stages of deciduous woods, historically maintained by coppicing (Cz, D) and forest pasture (A). Restoration of these traditional methods offers the only chance for survival ofE. maturnain Central Europe, and the butterfly may become a flagship for other threatened organisms of open‐canopy woodlands.
Legal considerations in cosmetic laser surgery
Authors: Goldberg David J
Published: June 2006

Cosmetic laser surgery is a continuously evolving field of medicine. According to the American Society for Dermatologic Surgery, over 100 million laser and light source cosmetic procedures were performed by its members. Procedures including hair removal, nonablative treatments, as well as removal of pigmented lesions, tattoos, and unwanted vascular lesions have revolutionized this field. With an increasing number of physicians and nonphysicians performing these procedures, and with the availability of increasingly powerful laser technologies, the potential for problems and their legal consequences continue to increase. This chapter will deal with the concept of negligence and the potential for a resultant medical malpractice that may arise in such a setting. An understanding of the basic principles of a cause of action in medical malpractice will likely protect a physician from losing such a case in a court of law.