bluuebunny/crossref_metadata_2025 huggingface dataset:
Can a common bird species be used as a surrogate to draw insights for the conservation of a rare species? A case study from the fragmented Taita Hills, Kenya
Authors: Githiru Mwangi , Matthysen Erik , Lens Luc , Bennun Leon A.
Published: May 2007

Sound knowledge of underlying mechanisms is essential for understanding how species respond to habitat fragmentation. Because most threatened species are typically the first ones to suffer local extinctions with forest fragmentation, studying why they fare poorly at the broader landscape scale is difficult. Related, sympatric but common species may be useful surrogates if they can provide insights germane for the conservation of rarer species. We illustrate this using a case study from the highly fragmented Taita Hills forests, south-eastern Kenya, of the Critically Endangered Taita thrush Turdus helleri and the more common white-starred robin Pogonocichla stellata as the surrogate. The responses of the thrush to habitat disturbance were in the same direction as the surrogate robin (e.g. higher fluctuating asymmetry, lower effective population densities and male-biased sex ratios), albeit they were detected sooner and were more severe because of its lower dispersal capacity. The key conservation measures proposed from the surrogate study largely matched those based on an independent evaluation of the thrush data. Additionally, the surrogate provided extra insights into the potential solutions for problems facing the thrush, and provided a base that could be used as a template for restoring the thrush populations in this area. Thus, our findings support the use of surrogate species in the conservation of sympatric related species in fragmented landscapes. We contend that this approach is also applicable for allopatric related species where landscapes are similar, provided that detailed data on population patterns and processes for the surrogate are available.
Seven decades of institutional learning: managing alien plant invasions in the Kruger National Park, South Africa
Authors: Foxcroft Llewellyn C. , Freitag-Ronaldson Stefanie
Published: May 2007

Long-term ecological and economic sustainability will ultimately determine the outcome of any conservation management programme. Invasive alien plants, first recorded in the Kruger National Park, South Africa, in 1937, are now recognized as one of the greatest threats to the biodiversity of this Park. Such plants have been managed in the Park since 1956, with control advancing mainly through a process of trial and error. Refinement of invasive plant management strategies has resulted in an understanding of the target plants' biology and ecology, herbicide use and herbicide-plant interactions, as well as the plant-insect interactions of biological control. Careful integration of different control methods has proved essential to ensure the most appropriate use of techniques to deliver the best possible results from the resources available and achieve long-term sustainability. We outline the development of control efforts and current control programmes and the process of their incorporation into the institutional memory of Kruger National Park over the last 7 decades.
The role of the Wilms tumour gene (WT1) in normal and malignant haematopoiesis
Authors: Ariyaratana Suzie , Loeb David M.
Published: May 2007

In addition to its loss playing a pivotal role in the development of a childhood kidney malignancy, the Wilms tumour 1 gene (WT1) has emerged as an important factor in normal and malignant haematopoiesis. Preferentially expressed in CD34+haematopoietic progenitors and down-regulated in more-differentiated cells, the WT1 transcription factor has been implicated in regulation of apoptosis, proliferation and differentiation. Putative target genes, such asBCL2, MYC, A1and cyclin E, may cooperate withWT1to modulate cell growth. However, the effects of WT1 on target gene expression appear to be isoform-specific. Certain WT1 isoforms are over-represented in leukaemia, but the exact mechanisms underlying the role of WT1 in transformation remain unclear. The ubiquity of WT1 in haematological malignancies has led to efforts to exploit it as a marker for minimal residual disease and as a prognostic factor, with conflicting results. In vitro killing of tumour cells by WT1-specific CD8+cytotoxic T lymphocytes facilitated design of Phase I vaccine trials that showed clinical regression of WT1-positive tumours. Alternative methods employing WT1-specific immunotherapy are being investigated and might ultimately be used to optimise multimodal therapy of haematological malignancies.
Consensus Nomenclature for in vivo Imaging of Reversibly Binding Radioligands
Authors: Innis Robert B , Cunningham Vincent J , Delforge Jacques , Fujita Masahiro , Gjedde Albert , Gunn Roger N , Holden James , Houle Sylvain , Huang Sung-Cheng , Ichise Masanori , Iida Hidehiro , Ito Hiroshi , Kimura Yuichi , Koeppe Robert A , Knudsen Gitte M , Knuuti Juhani , Lammertsma Adriaan A , Laruelle Marc , Logan Jean , Maguire Ralph Paul , Mintun Mark A , Morris Evan D , Parsey Ramin , Price Julie C , Slifstein Mark , Sossi Vesna , Suhara Tetsuya , Votaw John R , Wong Dean F , Carson Richard E
Published: May 2007

An international group of experts in pharmacokinetic modeling recommends a consensus nomenclature to describe in vivo molecular imaging of reversibly binding radioligands.
Quantification of Cerebral Nicotinic Acetylcholine Receptors by PET Using 2-[18F]Fluoro-A-85380 and the Multiinjection Approach
Authors: Gallezot Jean-Dominique , Bottlaender Michel A , Delforge Jacques , Valette Héric , Saba Wadad , Dollé Frédéric , Coulon Christine M , Ottaviani Michèle P , Hinnen Françoise , Syrota André , Grégoire Marie-Claude
Published: May 2007

The multiinjection approach was used to study in vivo interactions between α4β2* nicotinic acetylcholine receptors and 2-[18F]fluoro-A-85380 in baboons. The ligand kinetics was modeled by the usual nonlinear compartment model composed of three compartments (arterial plasma, free and specifically bound ligand in tissue). Arterial blood samples were collected to generate a metabolite-corrected plasma input function. The experimental protocol, which consisted of three injections of labeled or unlabeled ligand, was aiming at identifying all parameters in one experiment. Various parameters, including B'max (the binding sites density) and Kd VR (the apparent in vivo affinity of 2-[18F]fluoro-A-85380) could then be estimated in thalamus and in several receptor-poor regions. B'max estimate was 3.0±0.3 pmol/mL in thalamus, and ranged from 0.25 to 1.58 pmol/ml_ in extrathalamic regions. Although Kd VR could be precisely estimated, the association and dissociation rate constants kon/ VR and koff could not be identified separately. A second protocol was then used to estimate koff more precisely in the thalamus. Having estimated all model parameters, we performed simulations of 2-[18F]fluoro-A-85380 kinetics to test equilibrium hypotheses underlying simplified approaches. These showed that a pseudo-equilibrium is quickly reached between the free and bound compartments, a favorable situation to apply Logan graphical analysis. In contrast, the pseudo-equilibrium between the plasma and free compartments is only reached after several hours. The ratio of radioligand concentration in these two compartments then overestimates the true equilibrium value, an unfavorable situation to estimate distribution volumes from late images after a bolus injection.
Cerebral Ischemia Causes Dysregulation of Synaptic Adhesion in Mouse Synaptosomes
Authors: Costain Willard J , Rasquinha Ingrid , Sandhu Jagdeep K , Rippstein Peter , Zurakowski Bogdan , Slinn Jacqueline , MacManus John P , Stanimirovic Danica B
Published: May 2007

Synaptic pathology is observed during hypoxic events in the central nervous system in the form of altered dendrite structure and conductance changes. These alterations are rapidly reversible, on the return of normoxia, but are thought to initiate subsequent neuronal cell death. To characterize the effects of hypoxia on regulators of synaptic stability, we examined the temporal expression of cell adhesion molecules (CAMs) in synaptosomes after transient middle cerebral artery occlusion (MCAO) in mice. We focused on events preceding the onset of ischemic neuronal cell death (< 48 h). Synaptosome preparations were enriched in synaptically localized proteins and were free of endoplasmic reticulum and nuclear contamination. Electron microscopy showed that the synaptosome preparation was enriched in spheres (≈650 nm in diameter) containing secretory vesicles and postsynaptic densities. Forebrain mRNA levels of synaptically located CAMs was unaffected at 3 h after MCAO. This is contrasted by the observation of consistent downregulation of synaptic CAMs at 20 h after MCAO. Examination of synaptosomal CAM protein content indicated that certain adhesion molecules were decreased as early as 3 h after MCAO. For comparison, synaptosomal Agrn protein levels were unaffected by cerebral ischemia. Furthermore, a marked increase in the levels of p-Ctnnb1 in ischemic synaptosomes was observed. p-Ctnnb1 was detected in hippocampal fiber tracts and in cornu ammonis 1 neuronal nuclei. These results indicate that ischemia induces a dysregulation of a subset of synaptic proteins that are important regulators of synaptic plasticity before the onset of ischemic neuronal cell death.
Hypoxia-Induced Acute Mountain Sickness is Associated with Intracellular Cerebral Edema: A 3 T Magnetic Resonance Imaging Study
Authors: Schoonman Guus G , Sándor Peter S , Nirkko Arto C , Lange Thomas , Jaermann Thomas , Dydak Ulrike , Kremer Christine , Ferrari Michel D , Boesiger Peter , Baumgartner Ralf W
Published: May 2007

Acute mountain sickness is common among not acclimatized persons ascending to high altitude; the underlying mechanism is unknown, but may be related to cerebral edema. Nine healthy male students were studied before and after 6-h exposure to isobaric hypoxia. Subjects inhaled room air enriched with N2 to obtain arterial O2 saturation values of 75 to 80%. Acute mountain sickness was assessed with the environmental symptom questionnaire, and cerebral edema with 3 T magnetic resonance imaging in 18 regions of interest in the cerebral white matter. The main outcome measures were development of intra- and extracellular cerebral white matter edema assessed by visual inspection and quantitative analysis of apparent diffusion coefficients derived from diffusion-weighted imaging, and B0 signal intensities derived from T2-weighted imaging. Seven of nine subjects developed acute mountain sickness. Mean apparent diffusion coefficient increased 2.12% (baseline, 0.80±0.09; 6 h hypoxia, 0.81 ± 0.09; P = 0.034), and mean B0 signal intensity increased 4.56% (baseline, 432.1 ±98.2; 6 h hypoxia, 450.7 ± 102.5; P < 0.001). Visual inspection of magnetic resonance images failed to reveal cerebral edema. Cerebral acute mountain sickness scores showed a negative correlation with relative changes of apparent diffusion coefficients ( r = 0.83, P = 0.006); there was no correlation with relative changes of B0 signal intensities. In conclusion, isobaric hypoxia is associated with mild extracellular (vasogenic) cerebral edema irrespective of the presence of acute mountain sickness in most subjects, and severe acute mountain sickness with additional mild intracellular (cytotoxic) cerebral edema.
Introduction to the Biochemical Society Focused Meeting on Diet and Cardiovascular Health: Chylomicron Remnants and Their Emerging Roles in Vascular Dysfunction in Atherosclerosis
Authors: Botham K.M. , Wheeler-Jones C.P.D.
Published: May 2007

Although it has been known for many years that dietary lipids influence the development of atherosclerosis, in the past this has been attributed to their effects on blood cholesterol levels. Recent work, however, has shown that CMRs (chylomicron remnants), the lipoproteins which carry dietary lipids in the blood, potentially have a direct role in initiating atherogenesis by influencing vascular function. The Diet and Cardiovascular Health: Chylomicron Remnants and Their Emerging Roles in Vascular Dysfunction in Atherosclerosis Meeting focused attention on studies which have shown that CMRs influence vascular function via interactions with cells of the artery wall, including endothelial cells and macrophages, and also highlighted the part played by CMRs in the development of premature atherosclerosis in conditions such as the metabolic syndrome, which are an increasing cause of heart disease in developed countries.
Meal fatty acids and postprandial vascular reactivity
Authors: Jackson K.G. , Armah C.K. , Minihane A.M.
Published: May 2007

With increasing recognition of the pivotal role of vascular dysfunction in the progression of atherosclerosis, the vasculature has emerged as an important target for dietary therapies. Recent studies have indicated that chronic fatty acid manipulation alters vascular reactivity, when measured after an overnight fast. However, individuals spend a large proportion of the day in the postprandial (non-fasted) state. Several studies have shown that high fat meals can impair endothelial function within 3–4 h, a time period often associated with peak postprandial lipaemia. Although the impact of meal fatty acids on the magnitude and duration of the postprandial lipaemic response has been extensively studied, very little is known about their impact on vascular reactivity after a meal.
The induction of macrophage foam cell formation by chylomicron remnants
Authors: Botham K.M. , Moore E.H. , Pascale C. De , Bejta F.
Published: May 2007

The accumulation of foam cells in the artery wall causes fatty streaks, the first lesions in atherosclerosis. LDL (low-density lipoprotein) plays a major role in foam cell formation, although prior oxidation of the particles is required. Recent studies, however, have provided considerable evidence to indicate that CMRs (chylomicron remnants), which carry dietary lipids in the blood, induce foam cell formation without oxidation. We have shown that CMRs are taken up by macrophages and induce accumulation of both triacylglycerol and cholesterol, and that the rate of uptake and amount of lipid accumulated is influenced by the type of dietary fat in the particles. Furthermore, oxidation of CMRs, in striking contrast with LDL, inhibits, rather than enhances, their uptake and induction of lipid accumulation. In addition, the lipid accumulated after exposure of macrophages to CMRs is resistant to efflux, and this may be due to its sequestration in lysosomes. These findings demonstrate that CMRs induce pro-atherogenic changes in macrophages, and that their effects may be modulated by dietary factors including oxidized fats, lipophilic antioxidants and the type of fat present.
Mechanisms involved in chylomicron remnant lipid uptake by macrophages
Authors: Bravo E. , Napolitano M.
Published: May 2007

Although it is clear that chylomicron remnants are atherogenic, events leading to their internalization by macrophages are still debated. The lack of apoE (apolipoprotein E) in CRLPs (chylomicron remnant-like particles) reduces macrophage TAG (triacylglycerol) content by approx. 50%, suggesting that, as well as apoE-mediated endocytic uptake, apoE receptor-independent mechanisms are involved in the induction of foam cells by chylomicron remnants. Evaluation of the radioactivity associated with macrophages after incubation with CRLPs containing radiolabelled lipids suggests that the TAG and cholesterol carried by the particles have different kinetics of internalization. In addition, inhibition-based experiments indicate that cholesteryl ester-selective uptake and the extracellular lipoprotein lipase hydrolysis of TAG contribute to cholesterol and TAG accumulation respectively. Thus plasma TAG and cholesterol carried by remnant particles have to be considered two independent and non-interchangeable risk factors for athero-related diseases. In addition, the interaction between CRLPs and macrophages is modulated by dietary oxidized lipids and other lipophilic components. The presence of oxidized lipids, such as 7β-hydroxycholesterol and 7-oxocholesterol, the major cholesterol oxidation products found in atherosclerotic lesions, in CRLPs interferes with the mechanisms of their internalization, but does not cause quantitative changes of accumulated lipids, while the presence of the plant carotenoid, lycopene, or the antioxidant drug, probucol, enhances lipid accumulation in macrophages by increasing the rate of uptake of the particles and raising the intracellular synthesis of TAG. In conclusion, several mechanisms contribute to the macrophage uptake of postprandial lipoproteins, however, little is known of the balance and modulation between the different pathways.
Influence of minor components of olive oils on the composition and size of TRLs and on macrophage receptors involved in foam cell formation
Authors: Cabello-Moruno R. , Perona J.S. , Ruiz-Gutierrez V.
Published: May 2007

Metabolic and epidemiologic studies support the idea that the type of dietary fat is more important than the total amount of fat with respect to the development of atherosclerosis and the risk of cardiovascular heart disease. Dietary fat is carried in CMs (chylomicrons), which can be taken up by macrophages without need of further oxidation, leading to the formation of foam cells and initiating or aggravating the atherogenic process. Evidence from different studies has shown that dietary fat can influence the composition and size of TRLs (triacylglycerol-rich lipoproteins), which might modulate their atherogenicity to a certain extent. In particular, experiments in vitro have shown the anti-atherogenic effects of minor components from olive oil when forming part of TRL, as these particles give minor lipid components the opportunity to interact with the cells implicated in endothelial dysfunction and atherogenesis. However, the exact mechanisms mediating CM uptake by macrophages still remain unclear. Thus further studies are needed to understand how the modifications of TRL composition caused by dietary fats could modulate the expression of macrophage receptors and foam cell formation, or even improve the atherogenic risk of these particles.
Measurement of endogenous and exogenous triacylglycerol kinetics in the fed and fasted states
Authors: Sun F. , Stolinski M. , Shojaee-Moradie F. , Umpleby A.M.
Published: May 2007

Emerging evidence has shown that an abnormal postprandial accumulation of dietary fat is atherogenic. However, there is a lack of data describing the mechanisms for accumulation of triacylglycerol (TAG) in the postprandial period. There is therefore a need to establish a specific measure of the kinetics of endogenous and exogenous TAG in the postprandial period.
Peptide α-helices for synthetic nanostructures
Authors: Ryadnov M.G.
Published: May 2007

Supramolecular structures arising from a broad range of chemical archetypes are of great technological promise. Defining such structures at the nanoscale is crucial to access principally new types of functional materials for applications in bionanotechnology. In this vein, biomolecular self-assembly has emerged as an efficient approach for building synthetic nanostructures from the bottom up. The approach predominantly employs the spontaneous folding of biopolymers to monodisperse three-dimensional shapes that assemble into hierarchically defined mesoscale composites. An immediate interest here is the extraction of reliable rules that link the chemistry of biopolymers to the mechanisms of their assembly. Once established these can be further harnessed in designing supramolecular objects de novo. Different biopolymer classes compile a rich repertoire of assembly motifs to facilitate the synthesis of otherwise inaccessible nanostructures. Among those are peptide α-helices, ubiquitous folding elements of natural protein assemblies. These are particularly appealing candidates for prescriptive supramolecular engineering, as their well-established and conservative design rules give unmatched predictability and rationale. Recent developments of self-assembling systems based on helical peptides, including fibrous systems, nanoscale linkers and reactors will be highlighted herein.
Attachment of proteins to molecular printboards through orthogonal multivalent linkers
Authors: Ludden M.J.W. , Huskens J.
Published: May 2007

The attachment of proteins to a surface in such a way that the protein remains functional, is a key issue in many biotechnological processes. Here, we describe the controlled attachment with respect to kinetics, thermodynamics and orientation of SAv (streptavidin) through an orthogonal linker to β-cyclodextrin selfassembled monolayers. Both a univalent and a bivalent linker are used for this process. The immobilization strategy with the bivalent linker allows the stepwise adsorption of SAv on to the surface, allowing heterofunctionalization of SAv and thus the build-up of more complex bionanostructures at the surface.
Bio-based approaches to inorganic material synthesis
Authors: Tomczak M.M. , Slocik J.M. , Stone M.O. , Naik R.R.
Published: May 2007

Nature is an exquisite designer of inorganic materials using biomolecules as templates. Diatoms create intricate silica wall structures with fine features using the protein family of silaffins as templates. Marine sponges create silica spicules also using proteins, termed silicateins. In recent years, our group and others have used biomolecules as templates for the deposition of inorganic materials. In contrast with the traditional materials science approach, which requires high heat, extreme pH and non-aqueous solutions, the bio-based approaches allow the reactions to proceed usually at near ambient conditions. Additionally, the biological templates allow for the control of the inorganic nanoparticle morphology. The use of peptides and biomolecules for templating and assembling inorganics will be discussed here.
Putting the fizz into chemistry: applications of supercritical carbon dioxide in tissue engineering, drug delivery and synthesis of novel block copolymers
Authors: Tai H. , Popov V.K. , Shakesheff K.M. , Howdle S.M.
Published: May 2007

This paper describes the recent progress at Nottingham towards the exploitation of the unique properties of scCO2 (supercritical carbon dioxide) for the preparation of polymeric scaffolds for tissue engineering applications and new devices for controlled drug delivery, as well as the synthesis of novel block copolymers by the combination of eROP (enzymatic ring opening polymerization) and controlled polymerization methods for the potential use as drug carriers.
Self-assembling layers created by membrane proteins on gold
Authors: Shah D.S. , Thomas M.B. , Phillips S. , Cisneros D.A. , Le Brun A.P. , Holt S.A. , Lakey J.H.
Published: May 2007

Membrane systems are based on several types of organization. First, amphiphilic lipids are able to create monolayer and bilayer structures which may be flat, vesicular or micellar. Into these structures membrane proteins can be inserted which use the membrane to provide signals for lateral and orientational organization. Furthermore, the proteins are the product of highly specific self-assembly otherwise known as folding, which mostly places individual atoms at precise places in three dimensions. These structures all have dimensions in the nanoscale, except for the size of membrane planes which may extend for millimetres in large liposomes or centimetres on planar surfaces such as monolayers at the air/water interface. Membrane systems can be assembled on to surfaces to create supported bilayers and these have uses in biosensors and in electrical measurements using modified ion channels. The supported systems also allow for measurements using spectroscopy, surface plasmon resonance and atomic force microscopy. By combining the roles of lipids and proteins, highly ordered and specific structures can be self-assembled in aqueous solution at the nanoscale.
Three-dimensional cell culture of chondrocytes on modified di-phenylalanine scaffolds
Authors: Jayawarna V. , Smith A. , Gough J.E. , Ulijn R.V.
Published: May 2007

The design of self-assembled peptide-based structures for three-dimensional cell culture and tissue repair has been a key objective in biomaterials science for decades. In search of the simplest possible peptide system that can self-assemble, we discovered that combinations of di-peptides that are modified with aromatic stacking ligands could form nanometre-sized fibres when exposed to physiological conditions. For example, we demonstrated that a number of Fmoc (fluoren-9-ylmethyloxycarbonyl) modified di- and tri-peptides form highly ordered hydrogels via hydrogen-bonding and π–π interactions from the fluorenyl rings. These highly hydrated gels allowed for cell proliferation of chondrocytes in three dimensions [Jayawarna, Ali, Jowitt, Miller, Saiani, Gough and Ulijn (2006) Adv. Mater. 18, 611–614]. We demonstrated that fibrous architecture and physical properties of the resulting materials were dictated by the nature of the amino acid building blocks. Here, we report the self-assembly process of three di-phenylalanine analogues, Fmoc-Phe-Phe-OH, Nap (naphthalene)-Phe-Phe-OH and Cbz (benzyloxycarbonyl)-Phe-Phe-OH, to compare and contrast the self-assembly properties and cell culture conditions attributable to their protecting group difference. Fibre morphology analysis of the three structures using cryo-SEM (scanning electron microscopy) and TEM (transmission electron microscopy) suggested fibrous structures with dramatically varying fibril dimensions, depending on the aromatic ligand used. CD and FTIR (Fourier-transform IR) data confirmed β-sheet arrangements in all three samples in the gel state. The ability of these three new hydrogels to support cell proliferation of chondrocytes was confirmed for all three materials.
An alternative strategy for inhibiting multidrug-resistant mutants of the dimeric HIV-1 protease by targeting the subunit interface
Authors: Bannwarth L. , Reboud-Ravaux M.
Published: May 2007

Mutations that occur in response to the HIV-1 protease inhibitors are responsible for the development of multidrug cross-resistance to these antiproteases in AIDS treatment. One alternative to inhibiting the active site of HIV-1 protease is to target the dimer interface of the homodimeric enzyme at the antiparallel β-sheet formed by the interdigitation of the C- and N-ends of each monomer. This region is highly conserved and is responsible for approx. 75% of the dimer-stabilization energy. The strategies that have been used to design small molecules to target the interface antiparallel β-sheet have produced lipopeptides, guanidinium derivatives and peptides (or peptidomimetics) cross-linked with spacers. The mechanism of inhibition was determined using a combination of kinetic and biophysical methods. These dimerization inhibitors proved equally active in vitro against both wild-type and mutated proteases. They are therefore promising alternatives to active-site-directed inhibitors in AIDS therapy. Disruption of protein–protein interactions by small molecules is a new way to obtain potentially therapeutic molecules.
Neuropeptidomics: expanding proteomics downwards
Authors: Svensson M. , Sköld K. , Nilsson A. , Fälth M. , Svenningsson P. , Andrén P.E.
Published: May 2007

Biological function is mainly carried out by a dynamic population of proteins and peptides which may be used as markers for disease diagnosis, prognosis and as a guide for effective treatment. The study of proteins is called proteomics and it is generally performed by two-dimensional gel electrophoresis and mass spectrometric methods. However, gel-based proteomics is methodologically restricted from the low mass region, which includes important endogenous peptides. The study of endogenous peptides, peptidomics, is complicated by protein fragments produced post-mortem during conventional sample handling. Nanoflow liquid chromatography and MS, together with improved methods for sample preparation, have been used to semi-quantitatively monitor endogenous peptides in brain tissue. When rapidly heat-denatured brain tissue was analysed, these methods enabled simultaneous detection of hundreds of peptides and the identification of several endogenous peptides not previously described in the literature. In an application of the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model for Parkinson's disease, the expression of the small protein PEP-19 was compared with controls. The levels were found to be significantly decreased in the striatum of MPTP-treated animals.
Structural analysis of foot-and-mouth disease virus 3C protease: a viable target for antiviral drugs?
Authors: Curry S. , Roqué-Rosell N. , Sweeney T.R. , Zunszain P.A. , Leatherbarrow R.J.
Published: May 2007

Foot-and-mouth disease virus causes a major global agricultural problem that is difficult to control with existing vaccines. Structural analyses of the viral 3C protease not only have provided fresh insights into the catalytic mechanism of an unusual class of chymotrypsin-like cysteine proteases, but also are generating valuable information to drive the quest for effective antiviral therapies.
Organization of chromosomes in spermatozoa: an additional layer of epigenetic information?
Authors: Zalensky A. , Zalenskaya I.
Published: May 2007

Elaborate non-random organization of human sperm chromosomes at different structural levels, starting from the DNA packing by protamines up to the higher-order chromosome configuration and nuclear positioning of chromosome territories, has been discovered. Here, we put forward a hypothesis that the unique genome architecture in sperm provides a mechanism for orchestrated unpacking and ordered activation of the male genome during fertilization, thus offering an additional level of epigenetic information that will be deciphered in the descendant cells.
Sperm DNA fragmentation: awakening the sleeping genome
Authors: Shaman J.A. , Yamauchi Y. , Ward W.S.
Published: May 2007

We have recently demonstrated that mammalian spermatozoa have the ability to degrade their DNA by a mechanism that is similar to apoptosis in somatic cells. When this mechanism is activated, the DNA is first degraded into loop-sized fragments by TOP2B (topoisomerase IIB). This degradation, termed sperm chromatin fragmentation, can be reversed by EDTA, which causes TOP2B to religate the double-stranded breaks it originally produced. Under certain conditions, a nuclease then degrades the sperm DNA further, digesting the entire sperm genome. When mouse spermatozoa which have been treated to induce TOP2B-mediated DNA breaks are injected into oocytes, the paternal DNA is specifically and completely degraded. This total digestion of paternal DNA occurs at the time of DNA synthesis initiation. In the present study, we explore the significance of an active TOP2B in the nucleus for mouse sperm function.
Depressive symptoms and condom use with clients among female sex workers in China
Authors: Hong Yan , Li Xiaoming , Fang Xiaoyi , Zhao Ran
Published: May 2007

This study examines the association between depressive symptoms and condom use with clients among 278 female sex workers (FSW) in Guangxi, China. About 62% of these FSW had a high level of depressive symptoms (CES-D total score ≥16). Multiple logistic regression analyses indicated that FSW with high level of depressive symptoms were less likely to use condoms consistently (aOR = 0.50, 95% CI: 0.28–0.89) or use condoms properly (aOR = 0.44, 95% CI: 0.20–0.99). The findings suggested that HIV prevention programs targeted at FSW should take into consideration the level of depression they experience.
Chlamydia trachomatis prevalence in heterosexual men in Melbourne: a community-based study
Authors: Wade Amanda J. , Hocking Jane S. , Hellard Margaret E.
Published: May 2007

There is limited information about chlamydia prevalence in men. Our study aimed to measure the prevalence of chlamydia in 16–29-year-old heterosexual men. Recruitment was undertaken through urban sporting clubs. Participants were approached after training to complete a questionnaire and to provide a urine sample that was tested for Chlamydia trachomatis. Participants with positive results received treatment. Fifty participants were recruited and four were found to be infected (8.5%, 95% CI 2.76–21.27). There was a high prevalence of C. trachomatis in our study participants, highlighting the importance of including men in chlamydia response programs.
Chlamydia trachomatis infection among antenatal women in remote far west New South Wales, Australia
Authors: Lenton Jo-ann , Freedman Eleanor , Hoskin Kristie , Knight Vickie , Turley Darriea , Balding Bill , Kennedy Catherine , Chen Marcus Y. , McNulty Anna
Published: May 2007

Background: A prospective, cross-sectional study was undertaken of pregnant women attending antenatal services in the remote far west of New South Wales, Australia, between October 2004 and May 2006. Of 420 eligible women, 218 (52%) participated in the study. Six women (2.7%; 95% CI: 1.0–5.9) tested positive for Chlamydia trachomatis. The prevalence among pregnant, Indigenous women (n = 44) was 9.1% (95% CI: 2.5–21.7). Infection was significantly associated with Indigenous status (P = 0.003) and self-perceived risk for chlamydia (P = 0.05). Pregnant Indigenous women in remote areas may be at higher risk for chlamydia and targeted screening of this group should be considered.
Fc receptor-like 5 inhibits B cell activation via SHP-1 tyrosine phosphatase recruitment
Authors: Haga Christopher L. , Ehrhardt Götz R. A. , Boohaker Rebecca J. , Davis Randall S. , Cooper Max D.
Published: May 2007

The Fc receptor-like protein 5 (FCRL5) on B cells has both an immunoreceptor tyrosine-based activation motif (ITAM)-like sequence and two consensus immunoreceptor tyrosine-based inhibitory motifs (ITIM) in its cytoplasmic region. To evaluate its signaling potential, we expressed constructs for chimeric molecules composed of the cytoplasmic region of FCRL5 and the extracellular and transmembrane regions of the IgG Fc receptor FcγRIIB in a B cell line lacking an endogenous Fc receptor. Coligation of this fusion protein with the B cell receptor (BCR) inhibited BCR-mediated calcium mobilization, intracellular tyrosine phosphorylation, and Erk kinase activation. Our mutational analysis indicated that, whereas tyrosines in both the inhibitory and activation motifs are phosphorylated after ligation, only those in ITIMs influence BCR-mediated signaling. This FCRL5 inhibitory effect was mediated through dual ITIM recruitment of the SH2-containing protein tyrosine phosphatase, SHP-1, which in turn dephosphorylates the ITAM-based tyrosines in BCR Igα/Igβ heterodimers. An FCRL5 inhibitory effect on BCR signaling was likewise demonstrable for primary B cells. Although its ligand is presently unknown, we conclude that FCRL5 has the functional potential to serve as an inhibitory coreceptor on mature B cells in humans.
Location rather than CD62L phenotype is critical in the early establishment of influenza-specific CD8
+
T cell memory
Authors: Kedzierska Katherine , Stambas John , Jenkins Misty R. , Keating Rachael , Turner Stephen J. , Doherty Peter C.
Published: May 2007

The rapid recall of influenza virus-specific CD8
+
T cell effector function is protective, although our understanding of T cell memory remains incomplete. Recent debate has focused particularly on the CD62L lymph node homing receptor. The present analysis shows that although functional memory can be established from both CD62L
hi
and CD62L
lo
CD8
+
T cell subsets soon after initial encounter between naïve precursors and antigen, the optimal precursors are CD8
+
CD44
hi
CD25
lo
immune lymphocytes isolated from draining lymph nodes on day 3.5 after influenza virus infection. Analysis of primed T cells at different times after challenge indicates that the capacity to transfer memory is diminished at the peak of the primary cytotoxic T lymphocyte response, challenging speculations that the transition to memory first requires full differentiation to effector status. It seems that location rather than CD62Lhi/lo phenotype may be the more profitable focus for further dissection of the early establishment of T cell memory.
Insulin producing primary ovarian carcinoid tumor
Authors: MORKEN NILS‐HALVDAN , MAJAK BERNARD , KAHN JARL A.
Published: May 2007

Carcinoid tumors are slow growing and originate most frequently from gastrointestinal tissue (1). They may also appear in genital tissue like the ovaries. Primary ovarian carcinoid tumors are rare and contribute to less than 0.1% of all ovarian carcinomas (2).

We report the first case of insulin producing primary carcinoid tumor of the ovary, initially presented with amnesia and hypoglycemia and subsequently successfully treated with surgery.
Determination of a saliva cotinine cut‐off to distinguish pregnant smokers from pregnant non‐smokers
Authors: HEGAARD HANNE K. , KJÆRGAARD HANNE , MØLLER LARS F. , WACHMANN HENRIK , OTTESEN BENT
Published: May 2007

Background. Objective validation of smoking status is necessary. Earlier studies have used saliva cotinine concentrations between 14.2 and 30 ng/ml as cut‐off values to distinguish pregnant smokers from non‐smokers. However, these cut‐offs derive from studies including men and non‐pregnant women. This constitutes a problem, as recent studies have reported an accelerated metabolism in pregnant smokers. The aim of this study was to determine the optimum cut‐off cotinine level distinguishing pregnant smokers from pregnant non‐smokers. Methods. An observational study of 620 pregnant women, 359 self‐reported smokers and 261 self‐reported non‐smokers, with complete data on smoking status and saliva cotinine. The study was conducted at a large university hospital in Copenhagen, Denmark. Saliva was sampled at the first antenatal visit to the midwife and analyzed for cotinine level by gas chromatography. Participants completed a questionnaire immediately after the first visit. Results. A saliva cotinine cut‐off level of 13 ng/ml, corresponding to a sensitivity of 0.99 and specificity 0.98, was found to be the optimum cut‐off value separating pregnant smokers from non‐smokers. The sum of the sensitivity and specificity was at its maximum, 1.981. A 95% bootstrap confidence interval for the optimum cut‐off was (8–14 ng/ml). Conclusion. From the present data we recommend that in future studies on smoking cessation and pregnancy a cut‐off level of 13 ng/ml should be applied to distinguish between pregnant smokers and non‐smokers.
Denial of pregnancy ‐ characteristics of women at risk
Authors: WESSEL JENS , GAURUDER‐BURMESTER ANNETT , GERLINGER CHRISTOPH
Published: May 2007

Background.Denial of pregnancy is a woman's subjective lack of awareness of being pregnant. Denial throughout most of gestation or until delivery may be associated with significant risks for both mother and fetus. We wanted to investigate if maternal characteristics were useful in order to identify women at risk.Methods.A 1‐year prospective study was performed to recruit all women with denied pregnancies in Berlin, Germany. Maternal parameters were analysed and sociodemographic variables were compared with the regional birth register.Results.Sixty‐five women were recruited. Maternal age was between 15 and 44 years (median 27 years). Only 21 women had never been pregnant before. A large majority (83%) had a close partner. Three women had a psychiatric diagnosis of schizophrenia, and only one a current abuse of analgesics/tranquilizer.Conclusions.The group of women with denied pregnancy was heterogeneous, and a clear‐cut typology of a ‘pregnancy denier’ could not be established.
Variation in the amniotic fluid index following moderate physical activity in water during pregnancy
Authors: DERTKIGIL MARCIA SAN JUAN , CECATTI JOSE GUILHERME , SARNO MANUEL A.C. , CAVALCANTE SERGIO RICARDO , MARUSSI EMILIO FRANCISCO
Published: May 2007

Background. To evaluate changes in the amniotic fluid index (AFI) in low‐risk pregnant women before and after physical activity in water. Methods. This was a prospective trial with a before‐after approach. Women carried out moderate physical activity for 50 min, 3 times a week, while partially immersed in a swimming pool at 30°C. Women with 2 or more previous cesarean sections, with a high‐risk pregnancy or medical contra‐indications for physical activity were excluded. They were evaluated weekly by ultrasonography, from 20 weeks of pregnancy until delivery, to evaluate AFI before and after physical activity in water. A second observer also performed the AFI measurements, in order to establish inter‐observer variability. Analysis was performed using Student's t‐test or Wilcoxon tests. The linear correlation coefficient was used to assess inter‐observer variability. Results. A total of 25 pregnant women, 19–36 years of age, participated in the study between May 2003 and December 2004. A total of 232 ultrasonographic evaluations of AFI were carried out, a mean of 9.28 examinations per woman. Statistically significant increases in AFI were found following immersion at almost every week of pregnancy. The increase in AFI post‐immersion compared to pre‐immersion values ranged from 8.8 to 21.5%. There was good inter‐observer agreement. The correlation coefficient for the inter‐observer variability was 0.78 for pre‐immersion measurements, and 0.70 for post‐immersion measurements. Conclusions. Physical activity in water appears to significantly increase AFI. Since this is a non‐invasive therapy, we speculate that its clinical application may have significant value.
Are clinical symptoms more predictive than laboratory parameters for adverse maternal outcome in HELLP syndrome?
Authors: CAVKAYTAR SABRI , UGURLU EVIN NIL , KARAER ABDULLAH , TAPISIZ OMER LUTFI , DANISMAN NURI
Published: May 2007

Background. To determine the risk factors for adverse maternal outcome among women with HELLP syndrome. Methods. Sixty‐one pregnancies with hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome diagnosed antenatally were reviewed between 2003 and 2005. Maternal outcomes analyzed included eclampsia, abruptio placentae, disseminated intravascular coagulopathy (DIC), acute renal failure, need for transfusion of blood products, cesarean delivery and maternal death. Risk factors included maternal age, parity, gestational age at diagnosis, mean arterial blood pressure, headache, visual changes, nausea‐vomiting, epigastric pain, blood platelet count (≤50,000 versus>50,000 cells/mm3), and peak serum levels of aspartate aminotransferase. Results. Eclampsia was present in 52%, abruptio placentae in 11%, and DIC in 8% of 61 women with HELLP syndrome. 23% women required transfusion of blood products, 15% had acute renal failure, and 73% had cesarean section. Women with eclampsia had significantly more headache, nausea‐vomiting, visual changes and epigastric pain (p<0.05). Transfusion was significantly more frequent among women with blood platelet counts≤50,000 cells/mm3 (33 versus 21%; p<0.05). Women with a platelet count≤50,000 cells/mm3 had a higher rate of DIC compared to women with a platelet count>50,000 cells/mm3 (33.3 versus 3.8%; p<0.05). In women with acute renal failure and abruptio placentae, there were no significant differences in all the variables studied between those with and without these complications. Conclusions. Clinical symptoms, such as headache, visual changes, epigastric pain and nausea‐vomiting, are more predictive than laboratory parameters for adverse maternal outcomes.
The probability of successful IVF outcome after poor ovarian response*
Authors: SALDEEN PIA , KÄLLEN KARIN , SUNDSTRÖM PER
Published: May 2007

Background. To evaluate the relationship between age and poor ovarian response to pregnancy and cancellation rate after IVF stimulation. Methods. Poor ovarian response was defined as ≤5 follicles at ovum pick up (OPU). Out of 1,706 consecutive OPUs performed during 2003/2004, 290 poor responders were identified. This cohort of poor responders was divided into two groups, ‘older’ and ‘younger’, with a cut‐off at the median age of 37 years. The pregnancy and cancellation rates after OPU were analysed. Results. Women aged >37 years, who were poor responders, had a significantly lower pregnancy rate per OPU (3.0%) compared to normal to high responders in the same age group (22.1%, p<0.05). Also, 43.6% of women >37 years, who were classified as poor responders, did not receive an embryo transfer (ET), compared to 13.2% of normal to high responders in this age group (p<0.05). Poor responders who were ≤37 years had a significantly lower pregnancy rate/OPU compared to normal to high responders who were ≤37 years (14.0 versus 34.5%, p<0.05) and a higher cancellation rate (40.1 versus 10.5%). Logistic regression analyses showed strong correlations between treatment outcome and the number of oocytes, age, and the mean and cumulative FSH dose given. The variable with the strongest impact on negative outcome was an interactive term between mean age and mean‐FSH dose (p = 5.0×10−5), indicating that women >37 years, who receive high doses of FSH have a significantly poorer treatment outcome than can be explained by either age or FSH dose alone. Conclusions. Poor ovarian response after IVF stimulation requires thorough counselling prior to OPU, regardless of the woman's age. In poor responders >37 years of age, especially those who require high FSH doses, we suggest that the decision whether or not to proceed to OPU should include the couple after thorough counselling, even though the chance of successful outcome is extremely low.
Young women's sexual health and their views on dialogue with health professionals
Authors: WENDT EVA , HILDINGH CATHRINE , LIDELL EVY , WESTERSTÅHL ANNA , BAIGI AMIR , MARKLUND BERTIL
Published: May 2007

Background. Many women who experience sexual problems or who have been subjected to sexual abuse, do not seek help, and often health professionals avoid raising such issues. The aim of this study was to describe young women's sexual health and their views on a dialogue about aspects of sexuality in connection with a gynecologic examination. Method. Cross‐sectional study. Women, 23, 26 and 29 years of age, called for gynecologic screening between March and July 2006 (n = 488; response rate 75%). Descriptive statistics, multiple logistic regression and bivariate analysis were used. Results. The majority (95%) had a positive attitude towards sexuality, although many women reported sexual problems, and one‐fifth (22%) were dissatisfied with their sex life. Women considered it appropriate to be asked about sexuality in general (92%), while a majority (72%) found questions about sexual abuse appropriate. However, depending on the area, the majority (76–99%) had never been asked such questions. Demographic variables, aspects of life, sexuality and sexual abuse were irrelevant for whether women considered it appropriate to be asked questions about aspects of sexuality, by a midwife/doctor in connection with a gynecologic examination. Conclusion. The result can activate health professionals to initiate a dialogue about sexual issues among young women. In this way, many women who experience sexual problems or have been subjected to sexual abuse, may be provided the opportunity to improve their sexual health.