bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved dynamic geomagnetic rigidity cutoff modeling: Testing predictive accuracy
Authors: Clilverd Mark A. , Rodger Craig J. , Moffat‐Griffin Tracy , Verronen Pekka T.
Published: August 2007

In the polar atmosphere, significant chemical and ionization changes occur during solar proton events (SPEs). The access of solar protons to this region is limited by the dynamically changing geomagnetic field. In this study, we have used riometer absorption observations to investigate the accuracy of a model to predict Kp‐dependent geomagnetic rigidity cutoffs, and hence the changing proton fluxes. The imaging riometer at Halley, Antarctica is ideally situated for such a study, as the rigidity cutoff sweeps back and forth across the instrument's field of view, providing a severe test of the rigidity cutoff model. Using observations from this riometer during five solar proton events, we have confirmed the basic accuracy of this rigidity model. However, we find that the model can be improved by setting a lower Kp limit (i.e., Kp = 5 instead of 6) at which the rigidity modeling saturates. We also find that, for L > 4.5, the apparent L‐shell of the beam moves equatorward. In addition, the Sodankylä Ion and Neutral Chemistry (SIC) model is used to determine an empirical relationship between integral proton precipitation fluxes and nighttime ionosphere riometer absorption, in order to allow consideration of wintertime SPEs. We find that during the nighttime, the proton flux energy threshold is lowered to include protons with energies of >5 MeV in comparison with >10 MeV for the daytime empirical relationships. In addition, we provide an indication of the southern and northern geographic regions inside which SPEs play a role in modifying the neutral chemistry of the stratosphere and mesosphere.
The role of type I interferons in TLR responses
Authors: Noppert Susie J , Fitzgerald Katherine A , Hertzog Paul J
Published: July 2007

Recent advances in unravelling the complexities of the signalling pathways that constitute innate immunity have highlighted type I interferon as a key component in the response to infection. Here we focus on the emerging field of pattern‐recognition receptor signalling, specifically Toll‐like receptors and retinoic acid inducible gene‐like helicases, from the perspective of this 50‐year‐old cytokine. The type I interferon gene family encompasses more than 20 subtypes, whose nature and properties have been extensively studied during its relatively long history. In this review we update and integrate available data on the mechanics of activation of the interferon genes and the role of this cytokine family in the innate immune response.
Effects of Ru substitution for Mn on La0.7Sr0.3MnO3 perovskites
Authors: Wang L. M. , Lai Jian-Hong , Wu Jyh-Iuan , Kuo Y.-K. , Chang C. L.
Published: July 2007

We report the investigations of crystal structure, electrical resistivity (ρ), magnetization (M), x-ray photoelectron spectroscopy (XPS), specific heat (CP), thermal conductivity (κ), and thermoelectric power (TEP) on La0.7Sr0.3(Mn1−xRux)O3 (LSMRO) compounds with x=0 to 0.90. From the analyzes of crystal structure and magnetization measurements, it is inferred that Ru should have a mixed valence of Ru3+ and Ru4+ for LSMRO with low level of Ru substitution, and an additional mixed valence of Ru4+ and Ru5+ with higher Ru substitution. Such a finding is further confirmed by the XPS measurements. Besides, it is found that all measured physical properties undergo pronounced anomalies due to the ferromagnetic-paramagnetic phase transition, and the observed transport properties of LSMRO can be reasonably understood from the viewpoint of polaronic transport. The Curie temperatures TC determined from the magnetization measurements are consistently higher than those of the metal-insulator transitions TMI determined from the transport measurements. By replacing Mn with Ru, both TC and TMI decrease concurrently and the studied materials are driven toward the insulating phase with larger value of x. It is also found that the entropy change during the phase transition is reduced with more Ru substitution. These observations indicate that the existence of Ru has the effect of weakening the ferromagnetism and metallicity of the LSMRO perovskites.
Ductile ultrafine-grained Ti-based alloys with high yield strength
Authors: Zhang Lai-Chang , Lu Hai-Bo , Mickel Christine , Eckert Jürgen
Published: July 2007

The authors report on ductile ultrafine-grained (Ti0.72Fe0.28)100−xTax (0⩽x⩽4) alloys with not only high fracture strength but simultaneously high yield strength exceeding 2000MPa along with distinct plasticity, which are superior to high-strength Ti-based bulk metallic glasses and bimodal composites. All alloys mainly consist of β-Ti and FeTi solid solutions but display different microstructures. The alloys exhibit a high fracture strength >2500MPa and a high yield strength >2000MPa as well as large plasticity of ∼5%–7.5%. The microstructure-property correlation of these ultrafine-grained alloys is discussed.
Detection of nanomechanical vibrations by dynamic force microscopy in higher cantilever eigenmodes
Authors: San Paulo Alvaro , Black Justin P. , White Richard M. , Bokor Jeffrey
Published: August 2007

The authors present a method based on dynamic force microscopy to characterize subnanometer-scale mechanical vibrations in resonant micro- and nanoelectromechanical systems. The method simultaneously employs the first eigenmode of the microscope cantilever for topography imaging and the second eigenmode for the detection of the resonator vibration. Here, they apply this scheme for the characterization of a 1.6GHz film bulk acoustic resonator, showing that it overcomes the main limitations of acoustic imaging in contact-mode atomic force microscopy. The method provides nanometer-scale lateral resolution on arbitrarily high resonant frequency systems, which makes it applicable to a wide diversity of electromechanical systems.
Ti-rich and Cu-poor grain-boundary layers of CaCu3Ti4O12 detected by x-ray photoelectron spectroscopy
Authors: Wang C. , Zhang H. J. , He P. M. , Cao G. H.
Published: August 2007

Cleaved and polished surfaces of CaCu3Ti4O12 ceramics have been investigated by x-ray photoelectron spectroscopy (XPS) and energy dispersive x-ray spectroscopy (EDX), respectively. While EDX technique shows the identical CaCu3Ti4O12 stoichiometry for the two surfaces, XPS indicates that the cleaved surface with grain-boundary layers is remarkably Ti-rich and Cu-poor. The core-level spectrum of Cu 2p unambiguously shows the existence of monovalent copper only for the cleaved surface. Possible grain-boundary structure and its formation are discussed.
Highly sensitive optochemical gas detection by luminescent marine diatoms
Authors: Setaro A. , Lettieri S. , Maddalena P. , De Stefano L.
Published: August 2007

The modifications of photoluminescence properties of silica frustules of different marine diatoms induced by adsorption of nitrogen dioxide, methane, and carbon monoxide are reported. Different species of diatoms were found to exhibit different relative responses and different gas concentration ranges of sensitivity, depending on the morphology and porosity of their frustules. The photoluminescence quenching shows surface signature, exhibiting a coverage-limited kinetics according to a Langmuir mechanism. Due to the large variety of dimensions, porosities, and surface morphologies available in nature, these materials appear to be promising to improve the selectivity of gas sensing based on photoluminescence optochemical transduction.
A general model for allometric covariation in botanical form and function
Authors: Price Charles A. , Enquist Brian J. , Savage Van M.
Published: July 2007

The West, Brown, and Enquist (WBE) theory for the origin of allometric scaling laws is centered on the idea that the geometry of the vascular network governs how a suite of organismal traits covary with each other and, ultimately, how they scale with organism size. This core assumption has been combined with other secondary assumptions based on physiological constraints, such as minimizing the scaling of transport and biomechanical costs while maximally filling a volume. Together, these assumptions give predictions for specific “quarter-power” scaling exponents in biology. Here we provide a strong test of the core assumption of WBE by examining how well it holds when the secondary assumptions have been relaxed. Our relaxed version of WBE predicts that allometric exponents are highly constrained and covary according to specific quantitative functions. To test this core prediction, we assembled several botanical data sets with measures of the allometry of morphological traits. A wide variety of plant taxa appear to obey the predictions of the model. Our results (i) underscore the importance of network geometry in governing the variability and central tendency of biological exponents, (ii) support the hypothesis that selection has primarily acted to minimize the scaling of hydrodynamic resistance, and (iii) suggest that additional selection pressures for alternative branching geometries govern much of the observed covariation in biological scaling exponents. Understanding how selection shapes hierarchical branching networks provides a general framework for understanding the origin and covariation of many allometric traits within a complex integrated phenotype.
Translational up-regulation of the EGFR by tumor hypoxia provides a nonmutational explanation for its overexpression in human cancer
Authors: Franovic Aleksandra , Gunaratnam Lakshman , Smith Karlene , Robert Isabelle , Patten David , Lee Stephen
Published: August 2007

Overexpression of the EGF receptor (EGFR) is a recurrent theme in human cancer and is thought to cause aggressive phenotypes and resistance to standard therapy. There has, thus, been a concerted effort in identifying EGFR gene mutations to explain misregulation of EGFR expression as well as differential sensitivity to anti-EGFR drugs. However, such genetic alterations have proven to be rare occurrences in most types of cancer, suggesting the existence of a more general physiological trigger for aberrant EGFR expression. Here, we provide evidence that overexpression of wild-type EGFR can be induced by the hypoxic microenvironment and activation of hypoxia-inducible factor 2-α (HIF2α) in the core of solid tumors. Our data suggest that hypoxia/HIF2α activation represents a common mechanism for EGFR overexpression by increasing EGFR mRNA translation, thereby diminishing the necessity for gene mutations. This allows for the accumulation of elevated EGFR levels, increasing its availability for the autocrine signaling required for tumor cell growth autonomy. Taken together, our findings provide a nonmutational explanation for EGFR overexpression in human tumors and highlight a role for HIF2α activation in the regulation of EGFR protein synthesis.
LRH-1-mediated glucocorticoid synthesis in enterocytes protects against inflammatory bowel disease
Authors: Coste Agnes , Dubuquoy Laurent , Barnouin Romain , Annicotte Jean-Sebastien , Magnier Benjamin , Notti Mario , Corazza Nadia , Antal Maria Cristina , Metzger Daniel , Desreumaux Pierre , Brunner Thomas , Auwerx Johan , Schoonjans Kristina
Published: August 2007

Liver receptor homolog-1 (LRH-1) is a nuclear receptor involved in intestinal lipid homeostasis and cell proliferation. Here we show that haploinsufficiency of LRH-1 predisposes mice to the development of intestinal inflammation. Besides the increased inflammatory response, LRH-1 heterozygous mice exposed to 2,4,6-trinitrobenzene sulfonic acid show lower local corticosterone production as a result of an impaired intestinal expression of the enzymes CYP11A1 and CYP11B1, which control the local synthesis of corticosterone in the intestine. Local glucocorticoid production is strictly enterocyte-dependent because it is robustly reduced in epithelium-specific LRH-1-deficient mice. Consistent with these findings, colon biopsies of patients with Crohn's disease and ulcerative colitis show reduced expression of LRH-1 and genes involved in the production of glucocorticoids. Hence, LRH-1 regulates intestinal immunity in response to immunological stress by triggering local glucocorticoid production. These findings underscore the importance of LRH-1 in the control of intestinal inflammation and the pathogenesis of inflammatory bowel disease.
Hemodynamic cerebral correlates of sleep spindles during human non-rapid eye movement sleep
Authors: Schabus M. , Dang-Vu T. T. , Albouy G. , Balteau E. , Boly M. , Carrier J. , Darsaud A. , Degueldre C. , Desseilles M. , Gais S. , Phillips C. , Rauchs G. , Schnakers C. , Sterpenich V. , Vandewalle G. , Luxen A. , Maquet P.
Published: August 2007

In humans, some evidence suggests that there are two different types of spindles during sleep, which differ by their scalp topography and possibly some aspects of their regulation. To test for the existence of two different spindle types, we characterized the activity associated with slow (11–13 Hz) and fast (13–15 Hz) spindles, identified as discrete events during non-rapid eye movement sleep, in non-sleep-deprived human volunteers, using simultaneous electroencephalography and functional MRI. An activation pattern common to both spindle types involved the thalami, paralimbic areas (anterior cingulate and insular cortices), and superior temporal gyri. No thalamic difference was detected in the direct comparison between slow and fast spindles although some thalamic areas were preferentially activated in relation to either spindle type. Beyond the common activation pattern, the increases in cortical activity differed significantly between the two spindle types. Slow spindles were associated with increased activity in the superior frontal gyrus. In contrast, fast spindles recruited a set of cortical regions involved in sensorimotor processing, as well as the mesial frontal cortex and hippocampus. The recruitment of partially segregated cortical networks for slow and fast spindles further supports the existence of two spindle types during human non-rapid eye movement sleep, with potentially different functional significance.
Solution mapping of T cell receptor docking footprints on peptide-MHC
Authors: Varani Luca , Bankovich Alexander J. , Liu Corey W. , Colf Leremy A. , Jones Lindsay L. , Kranz David M. , Puglisi Joseph D. , Garcia K. Christopher
Published: August 2007

T cell receptor (TCR) recognition of peptide-MHC (pMHC) is central to the cellular immune response. A large database of TCR–pMHC structures is needed to reveal general structural principles, such as whether the repertoire of TCR/MHC docking modes is dictated by a “recognition code” between conserved elements of the TCR and MHC genes. Although ≈17 cocrystal structures of unique TCR–pMHC complexes have been determined, cocrystallization of soluble TCR and pMHC remains a major technical obstacle in the field. Here we demonstrate a strategy, based on NMR chemical shift mapping, that permits rapid and reliable analysis of the solution footprint made by a TCR when binding onto the pMHC surface. We mapped the 2C TCR binding interaction with its allogeneic ligand H–2Ld–QL9 and identified a group of NMR-shifted residues that delineated a clear surface of the MHC that we defined as the TCR footprint. We subsequently found that the docking footprint described by NMR shifts was highly accurate compared with a recently determined high-resolution crystal structure of the same complex. The same NMR footprint analysis was done on a high-affinity mutant of the TCR. The current work serves as a foundation to explore the molecular dynamics of pMHC complexes and to rapidly determine the footprints of many Ld-specific TCRs.
Dynamic donor–acceptor [2]catenanes
Authors: Miljanić Ognjen Š , Stoddart J. Fraser
Published: August 2007

Donor–acceptor [2]catenanes based on cyclobis(paraquat-
p
-phenylene) as the π-acceptor ring have been used prominently in the construction of functional molecular devices. We report here their thermodynamically controlled synthesis from isolated π-donor and π-acceptor rings under the catalytic influence of tetra butylammonium iodide. The initial nucleophilic attack of iodide ion, which opens up the π-acceptor ring, is followed by complexation to the π-donor ring and the subsequent catenation of the π-donor ring by the π-acceptor ring [2]catenane. The reaction is general in scope and proceeds in high yields, without giving rise to side-products.
Antifungal hydrogels
Authors: Zumbuehl Andreas , Ferreira Lino , Kuhn Duncan , Astashkina Anna , Long Lisa , Yeo Yoon , Iaconis Tiffany , Ghannoum Mahmoud , Fink Gerald R. , Langer Robert , Kohane Daniel S.
Published: July 2007

Fungi are increasingly identified as major pathogens in bloodstream infections, often involving indwelling devices. Materials with antifungal properties may provide an important deterrent to these infections. Here we describe amphogel, a dextran-based hydrogel into which amphotericin B is adsorbed. Amphogel kills fungi within 2 h of contact and can be reused for at least 53 days without losing its effectiveness against
Candida albicans
. The antifungal material is biocompatible
in vivo
and does not cause hemolysis in human blood. Amphogel inoculated with
C. albicans
and implanted in mice prevents fungal infection. Amphogel also mitigates fungal biofilm formation. An antifungal matrix with these properties could be used to coat a variety of medical devices such as catheters as well as industrial surfaces.
Use of Decolonization to Prevent Staphylococcal Infections in Various Healthcare Settings: Results of an Emerging Infections Network Survey
Authors: West Sarah Klizas , Plantenga Melissa S. , Strausbaugh Larry J. ,   Infectious Diseases Society of America Emerging Infections Network
Published: August 2007

Less than 20% of infectious diseases consultants work in hospitals that routinely employ decolonization therapy for individuals with staphylococcal carriage undergoing elective surgical procedures or for infection control efforts to limit nosocomial transmission of methicillin-resistantStaphylococcus aureus(MRSA). However, infectious diseases consultants frequently encounter patients with recurrent MRSA furunculosis and attempt to decolonize them.
Outcomes for and Risk Factors Associated With Vancomycin-ResistantEnterococcus faecalisand Vancomycin-ResistantEnterococcus faeciumBacteremia in Cancer Patients
Authors: Ghanem G. , Hachem R. , Jiang Y. , Chemaly R. F. , Raad I.
Published: August 2007

Objective.

Vancomycin-resistant enterococci (VRE) are a major cause of nosocomial infection. We sought to compare vancomycin-resistant (VR)Enterococcus faecalisbacteremia and VREnterococcus faeciumbacteremia in cancer patients with respect to risk factors, clinical presentation, microbiological characteristics, antimicrobial therapy, and outcomes.

Methods.

We identified 210 cancer patients with VRE bacteremia who had been treated between January 1996 and December 2004; 16 of these 210 had VRE. faecalisbacteremia and were matched with 32 patients with VRE. faeciumbacteremia and 32 control patients. A retrospective review of medical records was conducted.

Results.

Logistic regression analysis showed that, compared with VRE. faecalisbacteremia, VRE. faeciumbacteremia was associated with a worse clinical response to therapy (odds ratio [OR], 0.3 [95% confidence interval (CI), 0.07-0.98];P= .046) and a higher overall mortality rate (OR, 8.3 [95% CI, 1.9-35.3];P= .004), but the VRE-related mortality rate did not show a statistically significant difference (OR, 6.8 [95% CI, 0.7-61.8];P= .09). Compared with control patients, patients with VRE. faecalisbacteremia were more likely to have received an aminoglycoside in the 30 days before the onset of bacteremia (OR, 5.8 [95% CI, 1.2-27.6];P= .03), whereas patients with VRE. faeciumbacteremia were more likely to have received a carbapenem in the 30 days before the onset of bacteremia (OR, 11.7 [95% CI, 3.6-38.6];P<.001). In a multivariate model that compared patients with VRE. faeciumbacteremia and control patients, predictors of mortality included acute renal failure on presentation (OR, 15.1 [95% CI, 2.3-99.2];P= .004) and VRE. faeciumbacteremia (OR, 11 [95% CI, 2.7-45.1];P<.001). No difference in outcomes was found between patients with VRE. faecalisbacteremia and control patients.

Conclusions.

VRE. faeciumbacteremia in cancer patients was associated with a poorer outcome than was VRE. faecalisbacteremia. Recent receipt of carbapenem therapy was an independent risk factor for VRE. faeciumbacteremia, and recent receipt of aminoglycoside therapy was independent risk factor forE. faecalisbacteremia.
Shu Proteins Promote the Formation of Homologous Recombination Intermediates That Are Processed by Sgs1-Rmi1-Top3
Authors: Mankouri Hocine W. , Ngo Hien-Ping , Hickson Ian D.
Published: August 2007

CSM2, PSY3, SHU1, and SHU2 (collectively referred to as the SHU genes) were identified in Saccharomyces cerevisiae as four genes in the same epistasis group that suppress various sgs1 and top3 mutant phenotypes when mutated. Although the SHU genes have been implicated in homologous recombination repair (HRR), their precise role(s) within this pathway remains poorly understood. Here, we have identified a specific role for the Shu proteins in a Rad51/Rad54-dependent HRR pathway(s) to repair MMS-induced lesions during S-phase. We show that, although mutation of RAD51 or RAD54 prevented the formation of MMS-induced HRR intermediates (X-molecules) arising during replication in sgs1 cells, mutation of SHU genes attenuated the level of these structures. Similar findings were also observed in shu1 cells in which Rmi1 or Top3 function was impaired. We propose a model in which the Shu proteins act in HRR to promote the formation of HRR intermediates that are processed by the Sgs1-Rmi1-Top3 complex.
Bayesian inference for dynamic transcriptional regulation; the Hes1 system as a case study
Authors: Heron Elizabeth A. , Finkenstädt Bärbel , Rand David A.
Published: July 2007

Motivation: In this study, we address the problem of estimating the parameters of regulatory networks and provide the first application of Markov chain Monte Carlo (MCMC) methods to experimental data. As a case study, we consider a stochastic model of the Hes1 system expressed in terms of stochastic differential equations (SDEs) to which rigorous likelihood methods of inference can be applied. When fitting continuous-time stochastic models to discretely observed time series the lengths of the sampling intervals are important, and much of our study addresses the problem when the data are sparse.

Results: We estimate the parameters of an autoregulatory network providing results both for simulated and real experimental data from the Hes1 system. We develop an estimation algorithm using MCMC techniques which are flexible enough to allow for the imputation of latent data on a finer time scale and the presence of prior information about parameters which may be informed from other experiments as well as additional measurement error.

Availability: supplementary information is submitted with the article.

Contact: B.F.Finkenstadt@Warwick.ac.uk

Supplementary information: Supplementary data are available at Bioinformatics online.
Data-based identifiability analysis of non-linear dynamical models
Authors: Hengl S. , Kreutz C. , Timmer J. , Maiwald T.
Published: July 2007

Motivation: Mathematical modelling of biological systems is becoming a standard approach to investigate complex dynamic, non-linear interaction mechanisms in cellular processes. However, models may comprise non-identifiable parameters which cannot be unambiguously determined. Non-identifiability manifests itself in functionally related parameters, which are difficult to detect.

Results: We present the method of mean optimal transformations, a non-parametric bootstrap-based algorithm for identifiability testing, capable of identifying linear and non-linear relations of arbitrarily many parameters, regardless of model size or complexity. This is performed with use of optimal transformations, estimated using the alternating conditional expectation algorithm (ACE). An initial guess or prior knowledge concerning the underlying relation of the parameters is not required. Independent, and hence identifiable parameters are determined as well. The quality of data at disposal is included in our approach, i.e. the non-linear model is fitted to data and estimated parameter values are investigated with respect to functional relations. We exemplify our approach on a realistic dynamical model and demonstrate that the variability of estimated parameter values decreases from 81 to 1% after detection and fixation of structural non-identifiabilities.

Availability: Our algorithm is written in Matlab and R. It is available from the authors on request. An implementation of ACE, written in Matlab as well as in C, is available online at www.stefanhengl.de

Contact:  hengl@fdm.uni-freiburg.de

Supplementary information: Supplementary data are available at Bioinformatics online.
Flavitrack: an annotated database of flavivirus sequences
Authors: Misra Milind , Schein Catherine H.
Published: July 2007

Motivation: Properly annotated sequence data for flaviviruses, which cause diseases, such as tick-borne encephalitis (TBE), dengue fever (DF), West Nile (WN) and yellow fever (YF), can aid in the design of antiviral drugs and vaccines to prevent their spread. Flavitrack was designed to help identify conserved sequence motifs, interpret mutational and structural data and track evolution of phenotypic properties.

Summary: Flavitrack contains over 590 complete flavivirus genome/protein sequences and information on known mutations and literature references. Each sequence has been manually annotated according to its date and place of isolation, phenotype and lethality. Internal tools are provided to rapidly determine relationships between viruses in Flavitrack and sequences provided by the user.

Availability:  http://carnot.utmb.edu/flavitrack

Contact:  chschein@utmb.edu

Supplementary information:  http://carnot.utmb.edu/flavitrack/B1S1.html
Reorganization of learning-associated prefrontal synaptic plasticity between the recall of recent and remote fear extinction memory
Authors: Hugues Sandrine , Garcia Rene
Published: August 2007

We have previously shown that fear extinction is accompanied by an increase of synaptic efficacy in inputs from the ventral hippocampus (vHPC) and mediodorsal thalamus (MD) to the medial prefrontal cortex (mPFC) and that disrupting these changes to mPFC synaptic transmission compromises extinction processes. The aim of this study was to examine whether these extinction-related changes undergo further plasticity as the memory of extinction becomes more remote. Changes in synaptic efficacy in both vHPC-mPFC and MD-mPFC inputs were consequently analyzed when the memory was either 1 d or 7 d old. Increases of synaptic efficacy in the vHPC-mPFC pathway were observed when the memory was 1 d old, but not 7 d after initial extinction. In contrast, potentiation of synaptic efficacy in the MD-mPFC pathway increased over time. In rats that received low-frequency vHPC stimulation immediately after extinction, both vHPC-mPFC and MD-mPFC inputs failed to develop potentiation, and the recall of extinction (both recent and remote memories) was impaired. These findings suggest that post-extinction potentiation in vHPC-mPFC inputs may be necessary for both the recall of recent memory and post-extinction potentiation in the MD-mPFC inputs. This late potentiation process may be required for the recall of remote extinction memory.
Immunodeficiency and immunotherapy in multiple myeloma
Authors: Pratt Guy , Goodyear Oliver , Moss Paul
Published: August 2007

Multiple myeloma is a malignant tumour of plasma cells that remains incurable for the vast majority of patients, with a median survival of 2–3 years. It is characterized by the patchy accumulation of tumour cells within bone marrow leading to variable anaemia, bone destruction, hypercalcaemia, renal failure and infections. Immune dysfunction is an important feature of the disease and leads to infections that are both a major cause of morbidity and mortality and may promote tumour growth and resistance to chemotherapy. Numerous defects of the immune system have been described in multiple myeloma although the relative clinical importance of these remains elusive. There has been considerable interest in the identification of an autologous response against myeloma. Although T cells and humoral responses directed against myeloma‐associated antigens have been described, it is uncertain if the immune system plays a role in preventing or controlling myeloma cell growth. There is increasing interest in the potential role of immunotherapy but the success of these interventions is likely to be modified by the immunologically hostile environment associated with multiple myeloma. This review attempts to summarize the current knowledge relating to the immune defects found in multiple myeloma.
Haematopoietic stem cells participate in muscle regeneration
Authors: Abedi Mehrdad , Foster Bethany M. , Wood Kyle D. , Colvin Gerald A. , McLean Scott D. , Johnson Kevin W. , Greer Deborah A.
Published: August 2007

It has previously been shown that bone marrow cells contribute to skeletal muscle regeneration, but the nature of marrow cell(s) involved in this process is unknown. We used an immunocompetent and an immunocompromised model of bone marrow transplantation to characterize the type of marrow cells participating regenerating skeletal muscle fibres. Animals were transplanted with different populations of marrow cells from Green Fluorescent Protein (GFP) transgenic mice and the presence of GFP(+) muscle fibres were evaluated in the cardiotoxin‐injured tibialis anterior muscles. GFP(+) muscle fibres were found mostly in animals that received either CD45(−), lineage(−), c‐Kit(+), Sca‐1(+) or Flk‐2(+) populations of marrow cells, suggesting that haematopoietic stem cells (HSC) rather than mesenchymal cells or more differentiated haematopoietic cells are responsible for the formation of GFP(+) muscle fibres. Mac‐1 positive population of marrow cells was also associated with the emergence of GFP(+) skeletal muscle fibres. However, most of this activity was limited to either Mac‐1(+) Sca(+) or Mac‐1(+)c‐Kit(+) cells with long‐term haematopoietic repopulation capabilities, indicating a stem cell phenotype for these cells. Experiments in the immunocompromised transplant model showed that participation of HSC in the skeletal muscle fibre formation could occur without haematopoietic chimerism.
Measurement of global haemostasis in severe haemophilia A following factor VIII infusion
Authors: Lewis S. J. , Stephens E. , Florou G. , Macartney N. J. , Hathaway L. S. , Knipping J. , Collins P. W.
Published: August 2007

Patients with haemophilia requires different amounts of FVIII to prevent and treat bleeds. We hypothesise that this is because FVIII has variable effects on individual patients’ global haemostasis. Twelve patients with severe haemophilia A were infused with 50 IU/kg FVIII and thrombin generation in platelet rich (PRP) and platelet poor plasma (PPP) and velocity of changing clot elasticity were measured preinfusion and at nine subsequent time points over 72 h. Despite a close correlation between median FVIII and median initial rate of thrombin generation (R2 0·94), endogenous thrombin potential (ETP; R2 0·94) and peak thrombin (R2 0·91) in PPP, there was wide inter‐patient variability at each time point. There was, however, a highly predictable intra‐patient relationship between FVIII level and thrombin generation. Inter‐patient variability was due to both differences in FVIII levels and the variable effect FVIII had on an individuals’ thrombin generation. The utility of PRP was limited because, at low‐FVIII levels, only rate of thrombin generation was measurable. At low‐FVIII concentrations, the rate of thrombin generation in PPP was the most useful test whilst at higher levels ETP and peak thrombin could also be used.
High host specificity of obligate ectoparasites
Authors: DICK CARL W.
Published: July 2007

Abstract 1. Host specificity is the degree to which a parasite species occurs in association with a host species.

2. The degree to which obligate ectoparasites are host specific has been debated, but effects of sampling contamination were usually not addressed. Data from a controlled mammal–ectoparasite survey were used to assess host specificity of an obligate group of ectoparasites – streblid bat flies.

3. Host–parasite associations were categorised as primary or non‐primary. Non‐primary host associations were evaluated against primary associations via proportional comparison.

4. Results indicate that host specificity was high, exceeding previous reports. Natural host transfers were rare.

5. Non‐primary host associations were almost completely explained by disturbance transfers during sampling of the host or by contamination upon sampling the parasite. These conclusions likely hold for other taxa of obligate parasites.
Including species interactions in risk assessments for global change
Authors: SUTHERST R. W. , MAYWALD G. F. , BOURNE A. S.
Published: August 2007

Most ecological risk assessments for global change are restricted to the effects of trends in climate or atmospheric carbon dioxide. In order to move beyond investigation of the effects of climate alone, the climex™ model was extended to investigate the effects of species interactions, in the same or different trophic levels, along environmental gradients on a geographical scale. Specific needs that were revealed during the investigations include: better treatment of the effects of temporal and spatial climatic variation; elucidation of the nature of boundaries of species ranges; data to quantify the role of species traits in interspecies interactions; integrated observational, experimental, and modelling studies on mechanisms of species interactions along environmental gradients; and high‐resolution global environmental datasets. Greater acknowledgement of the shared limitations of simplified models and experimental studies is also needed. Above all, use of the scientific method to understand representative species ranges is essential. This requires the use of mechanistic approaches capable of progressive enhancement.
Interspecific phylogenetic analysis enhances intraspecific phylogeographical inference: a case study inPinus lambertiana
Authors: LISTON AARON , PARKER‐DEFENIKS MARIAH , SYRING JOHN V. , WILLYARD ANN , CRONN RICHARD
Published: July 2007

Pinus lambertiana(sugar pine) is an economically and ecologically important conifer with a 1600‐km latitudinal range extending from Oregon, USA, to northern Baja California, Mexico. Like all North American white pines (subsect.Strobus), sugar pine is highly susceptible to white pine blister rust, a disease caused by the fungusCronartium ribicola. We conducted a chloroplast DNA (cpDNA) survey ofPinussubsect.Strobuswith comprehensive geographical sampling ofP. lambertiana. Sequence analysis of 12 sugar pine individuals revealed strong geographical differentiation for two chloroplast haplotypes. A diagnostic restriction site survey of an additional 72 individuals demarcated a narrow 150‐km contact zone in northeastern California. In the contact zone, maternal (megagametophtye) and paternal (embryo) haplotypes were identified in 31 single seeds, demonstrating bidirectional pollen flow extending beyond the range of maternal haplotypes. The frequencies of theCr1allele for white pine blister rust major gene resistance, previously determined for 41 seed zones, differ significantly among seed zones that are fixed for the alternate haplotypes, or contain a mixture of both haplotypes. Interspecific phylogenetic analysis reveals that the northern sugar pine haplotype belongs to a clade that includesPinus albicaulis(whitebark pine) and all of the East Asian white pines. Furthermore, there is little cpDNA divergence between northern sugar pine and whitebark pine (dS = 0.00058). These results are consistent with a Pleistocene migration of whitebark pine into North America and subsequent chloroplast introgression from whitebark pine to sugar pine. This study demonstrates the importance of placing phylogeographical results in a broader phylogenetic context.
Disruption of arabinogalactan proteins disorganizes cortical microtubules in the root of Arabidopsis thaliana
Authors: Nguema‐Ona Eric , Bannigan Alex , Chevalier Laurence , Baskin Tobias I. , Driouich Azeddine
Published: August 2007

The cortical array of microtubules inside the cell and arabinogalactan proteins on the external surface of the cell are each implicated in plant morphogenesis. To determine whether the cortical array is influenced by arabinogalactan proteins, we first treated Arabidopsis roots with a Yariv reagent that binds arabinogalactan proteins. Cortical microtubules were markedly disorganized by 1 μmβ‐d‐glucosyl (active) Yariv but not by up to 10 μmβ‐d‐mannosyl (inactive) Yariv. This was observed for 24‐h treatments in wild‐type roots, fixed and stained with anti‐tubulin antibodies, as well as in living roots expressing a green fluorescent protein (GFP) reporter for microtubules. Using the reporter line, microtubule disorganization was evident within 10 min of treatment with 5 μm active Yariv and extensive by 30 min. Active Yariv (5 μm) disorganized cortical microtubules after gadolinium pre‐treatment, suggesting that this effect is independent of calcium influx across the plasma membrane. Similar effects on cortical microtubules, over a similar time scale, were induced by two anti‐arabinogalactan‐protein antibodies (JIM13 and JIM14) but not by antibodies recognizing pectin or xyloglucan epitopes. Active Yariv, JIM13, and JIM14 caused arabinogalactan proteins to aggregate rapidly, as assessed either in fixed wild‐type roots or in the living cells of a line expressing a plasma membrane‐anchored arabinogalactan protein from tomato fused to GFP. Finally, electron microscopy of roots prepared by high‐pressure freezing showed that treatment with 5 μm active Yariv for 2 h significantly increased the distance between cortical microtubules and the plasma membrane. These findings demonstrate that cell surface arabinogalactan proteins influence the organization of cortical microtubules.
An acute haemolytic transfusion reaction caused by anti‐Wra
Authors: Cherian G , Search S , Thomas E , Poole J , Davies S. V , Massey E
Published: July 2007

summary The Wright (Wra) antigen is found on the red blood cells of approximately 1 : 1000 Caucasians. Anti‐Wra has been reported to be present in 1 : 25 to 1 : 100 healthy blood donors and an even higher proportion of hospital patients. Incompatibility due to anti‐Wra might therefore be expected to occur in approximately 1 in 50 000 blood transfusions. Reports of haemolytic transfusion reactions (HTR) and haemolytic disease of the newborn due to anti‐Wra are, however, rare. We report an acute HTR due to anti‐Wra in a 58‐year‐old man with myelodysplastic syndrome associated with rigors, shortness of breath and a significant rise in serum bilirubin from 16 μmol L−1 pretransfusion to 110 μmol L−1 immediately afterwards. This was accompanied by the appearance of bilirubin and urobilinogen in his urine and a fall in haemoglobin of nearly 2 g dL−1 following the transfusion. Anti‐Wra was the only antibody implicated. When tested against the recipients plasma, Wr(a+) panel cells and the transfused unit responsible for the reaction were 2–3+ by indirect antiglobulin test (IAT) and the donation typed as Wr(a+). The recipient had the common Wr(a−) phenotype. The reaction resulted in the patient being admitted to hospital for 2 days. The increasing use of electronic issue may result in more frequent reports of reactions due to anti‐Wra using current screening cells.
Red cell damage after pumping by two infusion control devices (Arcomed VP 7000 and IVAC 572)
Authors: Parfitt H. S. , Davies S. V. , Tighe P. , Ewings P.
Published: July 2007

summary The aim of this study was to assess the performance in terms of red cell damage of two peristaltic volumetric infusion pumps – the Alaris IVAC 572 (San Diego, CA, USA) and Arcomed Volumed VP7000 (Regensdorf, Switzerland).

Various infusion pumps are available to transfuse blood at a predetermined rate. It is recommended that each machine should be individually assessed.

This experiment used six units of single‐donor‐transfusable packed red cells and ran each unit through both pumps. This was carried out at 9, 28 and 35 days post‐donation at rates from 2 to 150 mL h−1. Post‐pumping samples from these experiments, and a pre‐pumping sample in each case, were analysed for levels of potassium and free haemoglobin (Hb). They were also examined microscopically for evidence of cell damage.

Potassium levels showed no significant change with pumping on any occasion, but rose significantly as the samples aged. Free Hb showed some variation, but the only consistent finding was a similar rise in value with increasing pack age. Microscopic examination revealed no cell damage under any condition.

Both pumps performed to an acceptable level and appear safe to be used for red cell transfusion.
Efficacy of long‐term sublingual immunotherapy as an adjunct to pharmacotherapy in house dust mite‐allergic children with asthma
Authors: Ozdemir Cevdet , Yazi Didem , Gocmen Izlem , Yesil Ozlem , Aydogan Metin , Semic‐Jusufagic Aida , Bahceciler Nerin N. , Barlan Isil B.
Published: August 2007

Although sublingual immunotherapy (SLIT) is accepted to be a viable alternative of specific‐allergen immunotherapy, the efficacy of long‐term SLIT in asthmatic children is not well established. The efficacy of 3 yr of SLIT in addition to pharmacotherapy was compared with pharmacotherapy alone in a prospective, open, parallel‐group, controlled study. Children with asthma aged 4–16 yr, sensitive to house dust mite (HDM) were followed up for a run‐in period of 1 yr and then grouped as those who would receive SLIT + pharmacotherapy (n = 62) or pharmacotherapy alone (n = 28). All patients were evaluated based on symptom‐medication scores and lung function tests every 3 months, as well as skin‐prick test and serum total immunoglobulin E (IgE) levels annually for 3 yr. Children in the SLIT + pharmacotherapy group demonstrated significantly lower mean daily dose and annual duration of inhaled corticosteroid (ICS) usage when compared with controls. At the end of the 3 yr, within‐group comparisons revealed statistically significant decreases in the dose and duration of ICS only in the SLIT group. Furthermore, 52.4% of subjects in the SLIT + pharmacotherapy group were able to discontinue ICS treatment for at least 6 months, which was only 9.1% for the pharmacotherapy group. Three years of SLIT as an adjunct to pharmacotherapy resulted in reduction of both the duration and dose of ICSs and successful discontinuation of ICSs along with improvement in lung functions in HDM‐allergic children with asthma.
Continuation versus discontinuation of lithium in recurrent bipolar illness: a naturalistic study
Authors: Biel Matthew G , Peselow Eric , Mulcare Loretta , Case Brady G , Fieve Ron
Published: August 2007

Objectives:  Lithium's efficacy in prophylaxis of mood episodes in bipolar disorder (BD) is well established in the clinical trial setting, but may be less robust in routine clinical practice. We compared illness recurrence in bipolar patients naturalistically continued on or discontinued from lithium after an extended period of clinical stability on lithium monotherapy, and evaluated other potential risk factors for relapse.

Methods:  We followed 213 patients who were stable for 2 years on lithium monotherapy following resolution of acute symptoms marking their last manic episode. Based upon patient preference and clinical judgment, 159 patients were continued on lithium monotherapy and 54 patients were slowly discontinued. Survival differences between the continued and discontinued groups were assessed using the Kaplan–Meier product limit method, and risk factors for relapse were evaluated in Cox proportional hazards regression.

Results:  Patients continued on lithium prophylaxis experienced risk of recurrence equivalent to a third of that suffered by discontinued patients during the first year of treatment (0.15 versus 0.45), and significant survival differences persisted throughout follow‐up. Median survival time to illness recurrence for patients continued on lithium was 7.33 years [95% confidence interval (CI) 5.67–9.67]; that for patients discontinued from lithium was 1.33 years (95% CI 0.33–2.33). After controlling for all significant covariates, lithium discontinuation was associated with a hazard ratio of 4.85. Inter‐episode manic and depressive symptoms conferred increased risk for subsequent recurrence of illness in both groups, while lower lithium levels recorded during the two years of clinical stability preceding study onset were protective.

Conclusions:  Despite considerable rates of illness recurrence in both groups, those who continued on lithium sustained markedly lower rates of recurrence over a lengthy follow‐up period. Lithium discontinuation in BD after successful maintenance monotherapy is not advisable. If discontinuation is considered, lithium levels previously required to maintain clinical stability, and breakthrough or residual mood symptoms experienced during remission, should inform clinical decision making.
White matter abnormalities observed in bipolar disorder: a diffusion tensor imaging study
Authors: Yurgelun‐Todd Deborah A , Silveri Marisa M , Gruber Staci A , Rohan Michael L , Pimentel Patricia J
Published: August 2007

Objectives:  An increased incidence in white matter abnormalities is among the most frequently reported brain change in patients with bipolar disorder. The objective of the present study was to examine white matter tract integrity, using diffusion tensor imaging (DTI), in bipolar patients and healthy comparison subjects.

Methods:  Eleven DSM‐IV bipolar I patients and 10 healthy age‐ and sex‐matched controls were studied. DTI data were acquired on a 1.5 Tesla scanner. Fractional anisotropy (FA) and diffusivity (trace) were determined from axial images using region of interest (ROI) analyses. The ROIs were manually placed in the midline and forward projecting arms of the genu (anterior) and the midline of the splenium (posterior) of the corpus callosum.

Results:  Bipolar patients had significantly higher FA in the midline of the genu compared with healthy controls. Regional white matter differences were also observed, with significantly lower FA in the genu than forward projecting regions in both groups and lower FA in the genu than the splenium in controls.

Conclusions:  Diffusion tensor imaging revealed significant microstructural differences in the genu, as measured by elevated FA in bipolar patients compared with healthy controls. These preliminary findings further support the hypothesis that anomalous frontal brain mechanisms may be associated with bipolar disorder.