bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA search efficiency is modulated by charge composition and distribution in the intrinsically disordered tail
Authors: Vuzman Dana , Levy Yaakov
Published: November 2010

Intrinsically disordered tails are common in DNA-binding proteins and can affect their search efficiency on nonspecific DNA by promoting the brachiation dynamics of intersegment transfer. During brachiation, the protein jumps between distant DNA regions via an intermediate state in which the tail and globular moieties are bound to different DNA segments. While the disordered tail must be long and positively charged to facilitate DNA search, the effect of its residue sequence on brachiation is unknown. We explored this issue using the NK-2 and Antp homeodomain transcription factors. We designed 566 NK-2 tail-variants and 55 Antp tail-variants having different net charges and positive charge distributions and studied their dynamics and DNA search efficiencies using coarse-grained molecular dynamics simulations. More intersegment transfers occur when the tail is moderately positively charged and the positive charges are clustered together in the middle of the tail or towards its N terminus. The presence of a negatively charged residue does not significantly affect protein brachiation, although it is likely that the presence of many negatively charged residues will complicate the DNA search mechanism. A bioinformatic analysis of 1,384 wild-type homeodomains illustrates that the charge composition and distribution in their N-tail sequences are consistent with an optimal charge pattern to promote intersegment transfer. Our study thus indicates that the residue sequence of the disordered tails of DNA-binding proteins has unique characteristics that were evolutionarily selected to achieve optimized function and suggests that the sequence-structure-function paradigm known for structured proteins is valid for intrinsically disordered proteins as well.
Stable and dynamic cortical electrophysiology of induction and emergence with propofol anesthesia
Authors: Breshears Jonathan D. , Roland Jarod L. , Sharma Mohit , Gaona Charles M. , Freudenburg Zachary V. , Tempelhoff Rene , Avidan Michael S. , Leuthardt Eric C.
Published: November 2010

The mechanism(s) by which anesthetics reversibly suppress consciousness are incompletely understood. Previous functional imaging studies demonstrated dynamic changes in thalamic and cortical metabolic activity, as well as the maintained presence of metabolically defined functional networks despite the loss of consciousness. However, the invasive electrophysiology associated with these observations has yet to be studied. By recording electrical activity directly from the cortical surface, electrocorticography (ECoG) provides a powerful method to integrate spatial, temporal, and spectral features of cortical electrophysiology not possible with noninvasive approaches. In this study, we report a unique comprehensive recording of invasive human cortical physiology during both induction and emergence from propofol anesthesia. Propofol-induced transitions in and out of consciousness (defined here as responsiveness) were characterized by maintained large-scale functional networks defined by correlated fluctuations of the slow cortical potential (<0.5 Hz) over the somatomotor cortex, present even in the deeply anesthetized state of burst suppression. Similarly, phase-power coupling between θ- and γ-range frequencies persisted throughout the induction and emergence from anesthesia. Superimposed on this preserved functional architecture were alterations in frequency band power, variance, covariance, and phase–power interactions that were distinct to different frequency ranges and occurred in separable phases. These data support that dynamic alterations in cortical and thalamocortical circuit activity occur in the context of a larger stable architecture that is maintained despite anesthetic-induced alterations in consciousness.
Neural basis of the undermining effect of monetary reward on intrinsic motivation
Authors: Murayama Kou , Matsumoto Madoka , Izuma Keise , Matsumoto Kenji
Published: November 2010

Contrary to the widespread belief that people are positively motivated by reward incentives, some studies have shown that performance-based extrinsic reward can actually undermine a person's intrinsic motivation to engage in a task. This “undermining effect” has timely practical implications, given the burgeoning of performance-based incentive systems in contemporary society. It also presents a theoretical challenge for economic and reinforcement learning theories, which tend to assume that monetary incentives monotonically increase motivation. Despite the practical and theoretical importance of this provocative phenomenon, however, little is known about its neural basis. Herein we induced the behavioral undermining effect using a newly developed task, and we tracked its neural correlates using functional MRI. Our results show that performance-based monetary reward indeed undermines intrinsic motivation, as assessed by the number of voluntary engagements in the task. We found that activity in the anterior striatum and the prefrontal areas decreased along with this behavioral undermining effect. These findings suggest that the corticobasal ganglia valuation system underlies the undermining effect through the integration of extrinsic reward value and intrinsic task value.
Reconceptualizing the classification of PNAS articles
Authors: Airoldi Edoardo M. , Erosheva Elena A. , Fienberg Stephen E. , Joutard Cyrille , Love Tanzy , Shringarpure Suyash
Published: November 2010

PNAS article classification is rooted in long-standing disciplinary divisions that do not necessarily reflect the structure of modern scientific research. We reevaluate that structure using latent pattern models from statistical machine learning, also known as mixed-membership models, that identify semantic structure in co-occurrence of words in the abstracts and references. Our findings suggest that the latent dimensionality of patterns underlying PNAS research articles in the Biological Sciences is only slightly larger than the number of categories currently in use, but it differs substantially in the content of the categories. Further, the number of articles that are listed under multiple categories is only a small fraction of what it should be. These findings together with the sensitivity analyses suggest ways to reconceptualize the organization of papers published in PNAS.
Intron retention facilitates splice variant diversity in calcium-activated big potassium channel populations
Authors: Bell Thomas J. , Miyashiro Kevin Y. , Sul Jai-Yoon , Buckley Peter T. , Lee Miler T. , McCullough Ron , Jochems Jeanine , Kim Junhyong , Cantor Charles R. , Parsons Thomas D. , Eberwine James H.
Published: November 2010

We report that the stress axis–regulated exon (STREX)-containing calcium-activated big potassium (BKCa) channel splice variant expression and physiology are regulated in part by cytoplasmic splicing and intron retention. NextGen sequencing of the mRNA complement of pooled hippocampal dendrite samples found intron 17a (i17a), the intron immediately preceding STREX, in the BKCa mRNA. Further molecular analyses of i17a revealed that the majority of i17a-containing BKCa channel mRNAs associate with STREX. i17a siRNA treatment followed by STREX protein immunocytochemistry demonstrated both reduced levels and altered subcellular distribution of STREX-containing BKCa channel protein. Selective reduction of i17a-BKCa or STREX-BKCa mRNAs induced similar changes in the burst firing properties of hippocampal neurons. Collectively, these data show that STREX splice variant regulation via cytoplasmic splicing and intron retention helps generate STREX-dependent BKCa current diversity in hippocampal neurons.
MicroRNA-21 induces resistance to 5-fluorouracil by down-regulating human DNA MutS homolog 2 (hMSH2)
Authors: Valeri Nicola , Gasparini Pierluigi , Braconi Chiara , Paone Alessio , Lovat Francesca , Fabbri Muller , Sumani Khlea M. , Alder Hansjuerg , Amadori Dino , Patel Tushar , Nuovo Gerard J. , Fishel Richard , Croce Carlo M.
Published: November 2010

The overexpression of microRNA-21 (miR-21) is linked to a number of human tumors including colorectal cancer, where it appears to regulate the expression of tumor suppressor genes including p21, phosphatase and tensin homolog, TGFβ receptor II, and B-cell leukemia/lymphoma 2 -associated X protein. Here we demonstrate that miR-21 targets and down-regulates the core mismatch repair (MMR) recognition protein complex, human mutS homolog 2 (hMSH2) and 6 (hMSH6). Colorectal tumors that express a high level of miR-21 display reduced hMSH2 protein expression. Cells that overproduce miR-21 exhibit significantly reduced 5-fluorouracil (5-FU)-induced G2/M damage arrest and apoptosis that is characteristic of defects in the core MMR component. Moreover, xenograft studies demonstrate that miR-21 overexpression dramatically reduces the therapeutic efficacy of 5-FU. These studies suggest that the down-regulation of the MMR mutator gene associated with miR-21 overexpression may be an important clinical indicator of therapeutic efficacy in colorectal cancer.
p53-mediated apoptosis requires inositol hexakisphosphate kinase-2
Authors: Koldobskiy Michael A. , Chakraborty Anutosh , Werner J. Kent , Snowman Adele M. , Juluri Krishna R. , Vandiver M. Scott , Kim Seyun , Heletz Shira , Snyder Solomon H.
Published: November 2010

Inositol pyrophosphates have been implicated in numerous biological processes. Inositol hexakisphosphate kinase-2 (IP6K2), which generates the inositol pyrophosphate, diphosphoinositol pentakisphosphate (IP7), influences apoptotic cell death. The tumor suppressor p53 responds to genotoxic stress by engaging a transcriptional program leading to cell-cycle arrest or apoptosis. We demonstrate that IP6K2 is required for p53-mediated apoptosis and modulates the outcome of the p53 response. Gene disruption of IP6K2 in colorectal cancer cells selectively impairs p53-mediated apoptosis, instead favoring cell-cycle arrest. IP6K2 acts by binding directly to p53 and decreasing expression of proarrest gene targets such as the cyclin-dependent kinase inhibitor p21.
Development of self-reactive germinal center B cells and plasma cells in autoimmune FcγRIIB-deficient mice
Authors: Tiller Thomas , Kofer Juliane , Kreschel Cornelia , Busse Christian E. , Riebel Stefan , Wickert Susanne , Oden Felix , Mertes Maria M.M. , Ehlers Marc , Wardemann Hedda
Published: November 2010

Abnormalities in expression levels of the IgG inhibitory Fc gamma receptor IIB (FcγRIIB) are associated with the development of immunoglobulin (Ig) G serum autoantibodies and systemic autoimmunity in mice and humans. We used Ig gene cloning from single isolated B cells to examine the checkpoints that regulate development of autoreactive germinal center (GC) B cells and plasma cells in FcγRIIB-deficient mice. We found that loss of FcγRIIB was associated with an increase in poly- and autoreactive IgG+ GC B cells, including hallmark anti-nuclear antibody–expressing cells that possess characteristic Ig gene features and cells producing kidney-reactive autoantibodies. In the absence of FcγRIIB, autoreactive B cells actively participated in GC reactions and somatic mutations contributed to the generation of highly autoreactive IgG antibodies. In contrast, the frequency of autoreactive IgG+ B cells was much lower in spleen and bone marrow plasma cells, suggesting the existence of an FcγRIIB-independent checkpoint for autoreactivity between the GC and the plasma cell compartment.
CD14 is a coreceptor of Toll-like receptors 7 and 9
Authors: Baumann Christoph L. , Aspalter Irene M. , Sharif Omar , Pichlmair Andreas , Blüml Stephan , Grebien Florian , Bruckner Manuela , Pasierbek Pawel , Aumayr Karin , Planyavsky Melanie , Bennett Keiryn L. , Colinge Jacques , Knapp Sylvia , Superti-Furga Giulio
Published: November 2010

Recognition of pathogens by the innate immune system requires proteins that detect conserved molecular patterns. Nucleic acids are recognized by cytoplasmic sensors as well as by endosomal Toll-like receptors (TLRs). It has become evident that TLRs require additional proteins to be activated by their respective ligands. In this study, we show that CD14 (cluster of differentiation 14) constitutively interacts with the MyD88-dependent TLR7 and TLR9. CD14 was necessary for TLR7- and TLR9-dependent induction of proinflammatory cytokines in vitro and for TLR9-dependent innate immune responses in mice. CD14 associated with TLR9 stimulatory DNA in precipitation experiments and confocal imaging. The absence of CD14 led to reduced nucleic acid uptake in macrophages. Additionally, CD14 played a role in the stimulation of TLRs by viruses. Using various types of vesicular stomatitis virus, we showed that CD14 is dispensable for viral uptake but is required for the triggering of TLR-dependent cytokine responses. These data show that CD14 has a dual role in nucleic acid–mediated TLR activation: it promotes the selective uptake of nucleic acids, and it acts as a coreceptor for endosomal TLR activation.
The Effect of Legalization on Wages and Health Insurance: Evidence from the National Agricultural Workers Survey
Authors: Kandilov Amy M. G. , Kandilov Ivan T.
Published: November 2010

We estimate the effect of legalization on the wages and benefits of foreign‐born agricultural workers. Using data from the National Agricultural Workers Survey, we employ propensity score matching techniques to compare legal permanent residents in the United States with an appropriate control group of undocumented workers. Consistent with previous findings, we show that becoming a legal permanent resident results in a modest wage gain of about 5%. Further, we provide novel evidence that, in addition to higher wages, legalization leads to a significantly higher likelihood of receiving some other form of compensation, such as employer‐sponsored health insurance or a monetary bonus.
A Benefit‐Cost Analysis of U.S. Agricultural Trade Promotion
Authors: Kinnucan Henry W. , Cai Hailong
Published: November 2010

Subsidies for nonprice export promotion can harm domestic consumers by increasing price in the domestic market and by diverting funds from domestic market promotion. Taking these consumer impacts into account, we find that federal expenditures for nonprice export promotion of farm products may be too high.
SPLATCHE2: a spatially explicit simulation framework for complex demography, genetic admixture and recombination
Authors: Ray Nicolas , Currat Mathias , Foll Matthieu , Excoffier Laurent
Published: November 2010

Summary: SPLATCHE2 is a program to simulate the demography of populations and the resulting molecular diversity for a wide range of evolutionary scenarios. The spatially explicit simulation framework can account for environmental heterogeneity and fluctuations, and it can manage multiple population sources. A coalescent-based approach is used to generate genetic markers mostly used in population genetics studies (DNA sequences, SNPs, STRs or RFLPs). Various combinations of independent, fully or partially linked genetic markers can be produced under a recombination model based on the ancestral recombination graph. Competition between two populations (or species) can also be simulated with user-defined levels of admixture between the two populations. SPLATCHE2 may be used to generate the expected genetic diversity under complex demographic scenarios and can thus serve to test null hypotheses. For model parameter estimation, SPLATCHE2 can easily be integrated into an Approximate Bayesian Computation (ABC) framework.

Availability and implementation: SPLATCHE2 is a C++ program compiled for Windows and Linux platforms. It is freely available at www.splatche.com, together with its related documentation and example data.

Contact:  mathias.currat@unige.ch
Iatrogenic Femoral Neuropathy: Two Cases and Literature Update
Authors: Al-Ajmi Abdullah , Rousseff Rossen T , Khuraibet Adnan J
Published: November 2010

Iatrogenic femoral neuropathy is an uncommon surgical or obstetric complication that may be underreported. It results from compression, stretch, ischemia, or direct trauma of the nerve during hip arthroplasty, self-retaining retractor use in pelvicoabdominal surgery, lithotomy positioning for anesthesia or labor, and other more rare causes. Decreasing incidence of this complication after abdominal and gynecologic surgery but increase in its absolute numbers after hip arthroplasty has emerged over the last decade. We describe two illustrative cases related respectively to lithotomy positioning and self-retaining retractor use. The variability in clinical presentation of iatrogenic femoral nerve lesions, some new insights in their diverse pathophysiology, and in the diagnostic and treatment options are discussed with an update from the literature.
The modulated structure of the calcium aluminate Ca6(AlO2)12·Bi2O3
Authors: Pérez O. , Malo S. , Hervieu M.
Published: November 2010

Bismuth calcium aluminate, Bi2Ca6Al12O27, has been prepared as a ceramic and a single crystal. Analysis of reciprocal space using both electron and X-ray diffraction show an R-centred hexagonal unit cell: a = b = 17.3892 (4), c = 6.986 (1) Å. Additional weak reflections are observed; they require the introduction of a modulation wavevector q = 0.0453 (2)c* for indexing. The modulated structure has been solved using the superspace formalism [superspace group X\overline{3}(00\gamma)0]. A framework of corner-sharing AlO4 tetrahedra forms corrugated sixfold rings and uncommon triple rings. The Ca2+ cations exhibit an eightfold coordination sphere; edge-sharing CaO8 polyhedra form intertwinned zigzagging rows along c creating a three-dimensional net. Bi atoms are located in large hexagonal tunnels parallel to c and form Bi2O3 pairs, which adopt a trigonal bipyramidal configuration. The 6s
2 lone-electron pairs (Lp) point along c, in the opposite direction to the three Bi—O strong bonds to form two BiO3Lp tetrahedra with a common base. Different orientations of the Bi2O3Lp2 pairs, rotated by 60° around c, are observed. Their stacking modes in each of the hexagonal tunnels are described. The sequence of the stacking varies along c in each of the tunnels.
Electron density studies on hydrogen bonding in two chromone derivatives
Authors: Małecka Magdalena , Chęcińska Lilianna , Rybarczyk-Pirek Agnieszka , Morgenroth Wolfgang , Paulmann Carsten
Published: November 2010

The experimental electron densities of two chromone derivatives have been determined from X-ray synchrotron diffraction data at low temperature (100 K). Topological analysis of the electron density has been used to analyze the formation of resonance-assisted hydrogen bonds (RAHBs). Geometrical and topological parameters confirm π-electron delocalization within the hydrogen-bonded ring. In addition, weak C—H...O interactions were identified in both structures. Hydrogen-bond energies allowed medium and weak hydrogen bonds to be distinguished.
Interfering with interferon-γ signalling in intestinal epithelial cells: selective inhibition of apoptosis-maintained secretion of anti-inflammatory interleukin-18 binding protein
Authors: Schuhmann D , Godoy P , Weiß C , Gerloff A , Singer M V , Dooley S , Böcker U
Published: November 2010

The intestinal epithelial barrier represents an important component in the pathogenesis of inflammatory bowel diseases. Interferon (IFN)-γ, a T helper type 1 (Th1) cytokine, regulated by the interleukin (IL)-18/IL-18 binding protein (bp) system, modulates the integrity of this barrier. The aim of this work was to study functionally the consequences of IFN-γ on intestinal epithelial cells (IEC) and to interfere selectively with identified adverse IFN-γ effects. IEC lines were stimulated with IFN-γ. IL-18 and IL-18bp were assessed by enzyme-linked immunosorbent assay. Staining of phosphatidylserine, DNA laddering, lactate dehydrogenase (LDH) release, cleavage of poly-adenosine diphosphate-ribose-polymerase (PARP) and activation of caspase-3 were analysed to determine cell death. Inhibitors of tyrosine kinase, caspase-3 or p38 mitogen-activated kinase ((MAP) activity were used. Cytokines were measured in supernatants of colonic biopsies of healthy controls and inflammatory bowel disease (IBD) patients. In IEC lines, IFN-γ up-regulated IL-18bp selectively. Ex vivo, IFN-γ was present in supernatants from cultured biopsies and up-regulated with inflammation. Contrary to previous reports, IFN-γ alone induced apoptosis in IEC lines, as demonstrated by phosphatidylserin staining, DNA cleavage and LDH release. Further, activation of caspase-3, PARP cleavage and expression of pro-apoptotic Bad were induced. Partial inhibition of caspase-3 and of p38 but not JAK tyrosine kinase, preserved up-regulation of IL-18bp expression. Selective inhibition of IFN-γ mediated apoptosis, while preserving its beneficial consequences on the ratio of IL-18/IL-18bp, could contribute to the integrity of the mucosal barrier in intestinal inflammation.
Earthworm‐induced N mineralization in fertilized grassland increases both N2O emission and crop‐N uptake
Authors: Lubbers I. M. , Brussaard L. , Otten W. , Van Groenigen J. W.
Published: November 2010

Earthworms can increase plant nitrogen (N) availability by stimulating mineralization of organic matter. However, recent studies show that they can also cause elevated emission of the greenhouse gas nitrous oxide (N2O). It is unclear to what extent these two effects occur in fertilized grasslands, where earthworm densities are typically greatest. The aims of this study were therefore to (i) quantify the effects of earthworm activity on N uptake and N2O emissions in fertilized grasslands and (ii) link these effects to earthworm functional groups. In a 73‐day factorial mesocosm experiment, combinations of Lumbricus rubellus (Lr, epigeic), Aporrectodea longa (Al, anecic) and Aporrectodea caliginosa (Ac, endogeic) individuals were introduced into columns with grass growing on a fertilized (250 kg N ha−1) loamy soil. Introduction of Lr resulted in 50.8% (P < 0.001) larger N2O emissions and 5.4% (P = 0.032) larger grass biomass. Grass‐N uptake increased from 172 to 188 kg N ha−1 in the presence of Lr (P < 0.001), from 176 to 183 kg N ha−1 in the presence of Ac (P = 0.001), and from 168 to 199 kg N ha−1 when all three earthworm species were present (P = 0.006). Lr increased soil NH4+‐N concentrations (P = 0.010), further indicating enhanced mineralization of N caused by earthworm activity. We conclude that the previously observed beneficial effect of earthworm presence on plant‐N availability has a negative side‐effect: increased emissions of the mineralized N as N2O.
Expression of transient receptor potential vanilloid‐1 (TRPV1) in urothelial cancers of human bladder: relation to clinicopathological and molecular parameters
Authors: Kalogris Cristina , Caprodossi Sara , Amantini Consuelo , Lambertucci Federica , Nabissi Massimo , Morelli Maria Beatrice , Farfariello Valerio , Filosa Alessandra , Emiliozzi Maria Cristina , Mammana Gabriele , Santoni Giorgio
Published: November 2010

Kalogris C, Caprodossi S, Amantini C, Lambertucci F, Nabissi M, Morelli M B, Farfariello V, Filosa A, Emiliozzi M C, Mammana G & Santoni G (2010) Histopathology 57, 744–752 Expression of transient receptor potential vanilloid‐1 (TRPV1) in urothelial cancers of human bladder: relation to clinicopathological and molecular parameters

Aims:  To evaluate the expression of transient receptor potential vanilloid type‐1 channel protein (TRPV1) in normal and neoplastic urothelial tissues and to correlate TRPV1 expression with clinicopathological parameters and disease‐specific survival.

Methods and results:  TRPV1 expression was analysed in normal and neoplastic urothelial samples at both mRNA and protein levels by quantitative real time polymerase chain reaction (qPCR) and immunohistochemistry, respectively. TRPV1 downregulation was found in urothelial cancer (UC) specimens, which correlated with tumour progression. Moreover, TRPV1 mRNA levels were associated with clinicopathological parameters to assess the role of TRPV1 downregulation as a negative prognostic factor for survival. Kaplan–Meier survival analysis demonstrated a significantly shorter survival in patients showing TRPV1 mRNA downregulation. Multivariate Cox regression analysis indicated further that TRPV1 mRNA expression retained its significance as an independent risk factor.

Conclusions:  The progression of UC of human bladder is associated with a marked decrease in TRPV1 expression, with a progressive loss in high‐grade muscle invasive UC. Downregulation of TRPV1 mRNA expression may represent an independent negative prognostic factor for bladder cancer patients.
How important is peritoneal involvement in rectal cancer? A prospective study of 331 cases
Authors: Mitchard John R , Love Sharon B , Baxter Karol J , Shepherd Neil A
Published: November 2010

Mitchard J R, Love S B, Baxter K J & Shepherd N A  (2010) Histopathology57, 671–679  How important is peritoneal involvement in rectal cancer? A prospective study of 331 cases

Background and aims:  The importance of circumferential resection margin involvement in predicting locoregional recurrence and death from rectal cancer is well known. However, it is well accepted that cases of rectal carcinoma recur when this surgical margin is not compromised. The aim of this study was to analyse the influence of peritoneal involvement, among other clinicopathological variables, on locoregional recurrence and overall prognosis in an unselected prospective series of rectal cancer resections.

Methods and results:  This unselected prospective study assessed 331 rectal carcinoma cases from a colorectal cancer study that recruited more than 1000 cases. Meticulous pathological examination was performed by one pathologist, with particular attention paid to the peritoneal surface. All clinicopathological variables were entered into a database with comprehensive clinical follow‐up. Peritoneal involvement was a significant factor in prognosis on univariate analysis but not on multivariate analysis. However, in analysing the causes of locoregional recurrence specifically, it may have been a factor in causing this in up to half the cases.

Conclusions:  This study adds to the small amount of literature data on the potential importance of peritoneal involvement in predicting locoregional recurrence and overall prognosis, especially in upper rectal cancer.
Myxoid epithelioid sarcoma: a diagnostic challenge. A report on six cases
Authors: Flucke Uta , Hulsebos Theo J M , Van Krieken J Han J M , Mentzel Thomas
Published: November 2010

Flucke U, Hulsebos T J M, van Krieken J H J M & Mentzel T (2010) Histopathology57, 753–759  Myxoid epithelioid sarcoma: a diagnostic challenge. A report on six cases

Aims:  Epithelioid sarcoma (ES) is a distinct sarcoma‐type with a specific morphology and immunophenotype. Whereas focal myxoid change does occur, to our knowledge only two cases of ES with diffuse myxoid stroma have been reported previously. To characterize more clearly the myxoid variant of ES, we describe six additional cases and discuss the differential diagnoses.

Methods and results:  Cases were retrieved from the authors’ files and studied histologically, immunohistochemically and by molecular methods. The age of the patients, four females and two males, ranged from 16 to 74 years (median: 33 years). The neoplasms arose in an extremity (two cases), the abdominal wall, groin, perineum and shoulder (one case each). Histologically, four cases were of the conventional type, and two were of the proximal type and the immunophenotype was typical for ES. The tumour stroma, however, revealed prominent myxoid changes, ranging from 50 to 90% (median: 75%). Only one of the proximal type ES showed a SMARCB1 mutation, whereas the other tumours showed no mutation.

Conclusions:  The myxoid variant of ES represents a diagnostic challenge and may be confused with other benign and malignant myxoid neoplasms. The main differential diagnosis is myoepithelioma of the skin and soft tissue.
The PsbW protein stabilizes the supramolecular organization of photosystem II in higher plants
Authors: García‐Cerdán José G. , Kovács Laszlo , Tóth Tünde , Kereïche Sami , Aseeva Elena , Boekema Egbert J. , Mamedov Fikret , Funk Christiane , Schröder Wolfgang P.
Published: November 2010

PsbW, a 6.1‐kDa low‐molecular‐weight protein, is exclusive to photosynthetic eukaryotes, and associates with the photosystem II (PSII) protein complex. In vivo and in vitro comparison of Arabidopsis thaliana wild‐type plants with T‐DNA insertion knock‐out mutants completely lacking the PsbW protein, or with antisense inhibition plants exhibiting decreased levels of PsbW, demonstrated that the loss of PsbW destabilizes the supramolecular organization of PSII. No PSII‐LHCII supercomplexes could be detected or isolated in the absence of the PsbW protein. These changes in macro‐organization were accompanied by a minor decrease in the chlorophyll fluorescence parameter FV/FM, a strongly decreased PSII core protein phosphorylation and a modification of the redox state of the plastoquinone (PQ) pool in dark‐adapted leaves. In addition, the absence of PsbW protein led to faster redox changes in the PQ pool, i.e. transitions from state 1 to state 2, as measured by changes in stationary fluorescence (FS) kinetics, compared with the wild type. Despite these dramatic effects on macromolecular structure, the transgenic plants exhibited no significant phenotype under normal growth conditions. We suggest that the PsbW protein is located close to the minor antenna of the PSII complex, and is important for the contact and stability between several PSII‐LHCII supercomplexes.
Post‐transplant lymphoproliferative disorders in lung transplant recipients: 20‐yr experience at the University of Minnesota
Authors: Wudhikarn Kitsada , Holman C.J. , Linan M. , Blaes A.H. , Dunitz J.M. , Hertz M.E. , Peterson B.A.
Published: November 2010

Wudhikarn K, Holman CJ, Linan M, Blaes AH, Dunitz JM, Hertz ME, Peterson BA. Post‐transplant lymphoproliferative disorders in lung transplant recipients: 20‐yr experience at the University of Minnesota. Clin Transplant 2011: 25: 705–713. © 2010 John Wiley & Sons A/S.

Abstract: Post‐transplant lymphoproliferative disorders (PTLD) are potentially fatal complications of solid organ transplantation. The natural history of PTLD varies considerably among the different types of organs transplanted. While lung transplant recipients are highly susceptible to PTLD, there are only a few small studies that detail PTLD in this setting. We undertook this study to better describe the characteristics and treatment response in PTLD after lung transplantation. We conducted a retrospective chart review of lung and heart/lung‐transplant recipients between 1985 and 2008. A total of 32 cases (5%) of PTLD were identified in 639 patients. The median interval after transplantation to the diagnosis was 40 (3–242) months. Eight patients (25%) were diagnosed within one yr of transplantation and had PTLD predominantly within the thorax and allograft. Twenty‐four patients (75%) were diagnosed more than one yr after transplantation and their tumors mainly affected the gastrointestinal tract. Monomorphic PTLD, diffuse large B‐cell lymphoma, was diagnosed in 91%. Treatment of PTLD varied according to stage and clinical circumstances. Twenty‐four patients (75%) have died. The median overall survival was 10 (0–108) months. PTLD after lung transplantation remains a challenge as a result of its frequency, complexity and disappointing outcome.
Clinical outcomes of liver transplantation for HBV‐related hepatocellular carcinoma: data from the NIH HBV OLT study
Authors: Han Steven‐Huy , Reddy K. Rajender , Keeffe Emmet B. , Soldevila‐Pico Consuelo , Gish Robert , Chung Raymond T. , Degertekin Bulent , Lok Anna ,   the NIH HBV OLT Study Group
Published: November 2010

Han SH, Reddy KR, Keeffe EB, Soldevila‐Pico C, Gish R, Chung RT, Degertekin B, Lok ASF. Clinical outcomes of liver transplantation for HBV‐related hepatocellular carcinoma: data from the NIH HBV‐OLT study.  Clin Transplant 2011: 25: E152–E162. © 2010 John Wiley & Sons A/S.

Abstract:  Background:  Hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) is an indication for orthotopic liver transplantation (OLT) in patients with tumor stage within the United Network for Organ Sharing criteria. The number of patients listed for HBV‐related HCC is increasing, while the number of patients listed for HBV‐related cirrhosis is declining presumptively because of the availability of more effective oral nucleos(t)ide analogues. This study presents the final, long‐term outcome of patients transplanted for HBV‐related HCC in the National Institutes of Health (NIH) HBV OLT Study Group.

Results:  Ninety‐eight patients (52.4%) in the NIH HBV OLT cohort underwent OLT for HBV‐related HCC. With a mean follow‐up of 36.5 months post‐OLT, 12 (12.2%) patients developed recurrence of HCC. Multivariate analysis did not find a statistically significant role of gender, tumor stage at OLT, pre‐OLT HCC treatment, recurrence of HBV, or duration of HCC diagnosis pre‐OLT in predicting HCC recurrence. Serum alpha‐fetoprotein (AFP) level >200 ng/mL at transplant was found to be statistically significant in predicting HCC recurrence (p = 0.003). HCC recurrence was significantly associated with decreased post‐OLT survival.

Conclusion:  HCC is the most common indication for OLT in patients with chronic hepatitis B in the era of more effective oral antivirals. Serum AFP at the time of OLT is significantly associated with HCC recurrence.
Hyponatremia a valuable predictor of early mortality in patients with cirrhosis listed for liver transplantation
Authors: Moini Maryam , Hoseini‐Asl Mohammad Kazem , Taghavi Seyed Alireza , Sagheb Mohammad M. , Nikeghbalian Saman , Salahi Heshmatalah , Bahador Ali , Motazedian Motahareh , Jafari Peyman , Malek‐Hosseini Sayed Ali
Published: November 2010

Moini M, Hoseini‐Asl MK, Taghavi SA, Sagheb MM, Nikeghbalian S, Salahi H, Bahador A, Motazedian M, Jafari P, Malek‐Hosseini SA. Hyponatremia a valuable predictor of early mortality in patients with cirrhosis listed for liver transplantation. Clin Transplant 2011: 25: 638–645. © 2010 John Wiley & Sons A/S.

Abstract:  The current policy for organ allocation in liver transplantation is to give priority to the sickest patients mostly using model for end‐stage liver disease (MELD) score in ranking. However, other factors as serum sodium may be of value in predicting early mortality. In this single‐center study, patients with cirrhosis over age 14 on the liver transplant wait‐list from September 1998 to June 2007 were followed for six months from the time of listing to evaluate the value of hyponatremia on mortality. Of 612 listed patients, 51 were transplanted who were excluded from survival analysis and 55 died without transplantation within the first three months. The numbers of transplanted and dead patients during months 3–6 were 29 and 24, respectively. Both MELD score and serum sodium at the time of listing were independent predictors of early mortality. On bivariate analysis, serum sodium of <130 mEq/L beside MELD was a significant predictor of mortality within 90 and 180 d. Serum sodium level <135 mEq/L masked the difference in mortality between patients with refractory and non‐refractory ascites. Serum sodium level of <130 mEq/L and an increased MELD score are significant predictors of early mortality in patients listed for liver transplantation.
Long‐term outcome in 42 pediatric liver transplant patients with alpha 1‐antitrypsin deficiency: a single‐center experience
Authors: Hughes Michael G. , Khan Khalid M. , Gruessner Angelika C. , Sharp Harvey , Hill Mark , Jie Tun , Kandaswamy Raja , Humar Abhinav , Payne William D. , Gruessner Rainer W. G.
Published: November 2010

Hughes MG Jr, Khan KM, Gruessner AC, Sharp H, Hill M, Jie T, Kandaswamy R, Humar A, Payne WD, Gruessner RWG. Long‐term outcome in 42 pediatric liver transplant patients with alpha 1‐antitrypsin deficiency: a single‐center experience. Clin Transplant 2011: 25: 731–736. © 2010 John Wiley & Sons A/S.

Abstract:  Introduction:  We examined the long‐term outcome of transplantation for alpha 1‐antitrypsin deficiency (A1ATD).

Method:  Data were reviewed on 42 transplants in 35 children with A1ATD over 42 yr and compared with 129 transplants in 116 children with biliary atresia (BA).

Results:  Over 50% of patients were followed up for >10 yr. A1ATD were older than BA at transplantation, median age, 6.0 vs. 1.0 yr (p < 0.0001), and transplanted earlier in the course of liver failure (total bilirubin, 2.7 mg/dL [1.4–6.9] vs. 9.7 mg/dL [2.9–15.4], p = 0.005). Patient survival was greater in A1ATD than BA: one‐yr post‐transplant, 82.7% vs. 67.9%; five yr, 76.5% vs. 60.2%; and 10 yr, 76.5% vs. 55.9% (p = 0.03). Death‐censored graft survival was similar: one‐yr post‐transplant, 68.4% vs. 66.2%; five yr, 68.4% vs. 55.8%; and 10 yr, 68.4% vs. 52.5% (p = 0.2). Deaths were from infection, hemorrhage, and graft failure <6 months post‐transplant. Patient survival improved at five yr from 33.3% pre‐cyclosporine (CSA) (1969–1984) (n = 6) to 76.5% in the CSA era (1985–1994) (n = 17) and 100% with tacrolimus (1995–2006) (n = 12) (p = 0.007).

Conclusions:  The age at transplantation and the degree of liver dysfunction were related to the differences in graft and patient survival between A1AT and BA.
Detection of Bursaphelenchus xylophilus from old discs of dead Pinus armandii var. amamiana trees using a new detection kit
Authors: Kanetani S. , Kikuchi T. , Akiba M. , Nakamura K. , Ikegame H. , Tetsuka K.
Published: November 2010

We examined the effectiveness of a new Bursaphelenchus xylophilus detection kit, based on loop‐mediated isothermal amplification (LAMP), in old discs taken from the stem base of B. xylophilus‐infested dead trees of Pinus armandii var. amamiana (PAAm) occurring in their natural habitats. LAMP products, representing a past B. xylophilus infection, were detected in two consecutive trials from 16 of 20 discs collected from PAAm trees that died between 2003 and 2006. Bursaphelenchus xylophilus were more frequently detected using LAMP in wood samples taken from sapwood than from heartwood. No significant differences in the detection of B. xylophilus using LAMP were observed in relation to the disc collection time (from 3 to 6 years before the analysis). Bursaphelenchus xylophilus were not detected using LAMP in four discs, although a B. xylophilus infection had been confirmed for the original PAAm trees at the time they were found dead. This may have resulted from the small amount of wood chips needed for the LAMP test or the reduced number and uneven distribution of the nematode in the old dead trees. The results indicate that the new B. xylophilus detection kit will be a very efficient tool for conducting retrospective analysis of PAAm mortality factors.
Relationship between childhood short stature and academic achievement in adolescents and young adults – a longitudinal study
Authors: Tran Uyen N , O'Callaghan Michael J , Mamun Abdullah A , Najman Jake M , Williams Gail M , Bor William
Published: November 2010

Aim:  To determine if short stature at 14 or 21 years and patterns of ‘catch‐up’ growth from 5 to 14 or 21 years are related to academic achievement in adolescents.

Methods:  The Mater University of Queensland Study of Pregnancy is a longitudinal study of 7223 singleton infants born between 1981 and 1984. Data were available for cross‐sectional analyses of 3785 adolescents of whom 2149 were seen as young adults. Longitudinal patterns of growth were examined for 2936 subjects from 5 to 14 years and 1753 subjects from 5 to 21 years.

Results:  Adolescents or young adults with height <10th centile had a lower mean Wide Range Achievement Test (WRAT) score in adolescence and at 21 years than those of normal height (2.7 and 3.0 points, respectively) and increased odds of a WRAT score <85 (1.57 and 1.87, respectively) and learning difficulties (1.61 and 1.78, respectively). For growth patterns from 5 to 14 years, adolescents short at 5 years, irrespective of height at 14 years, had a lower mean WRAT score and increased odds of WRAT score <85 and learning difficulties. However, for growth patterns from 5 to 21 years, only the group short at both ages had increased learning difficulties.

Conclusions:  Youth short at 14 years or at 21 years and those persistently short have an increased prevalence of academic difficulties. Catch‐up growth by 21, although not 14 years, was associated with improved outcomes.
Lessons from the swine flu: Pandemic, panic and/or pandemonium?
Authors: Isaacs David
Published: November 2010

The 2009 pandemic of swine‐origin A/H1N1 influenza (swine flu) spread rapidly in Australia and there was a prolonged winter outbreak lasting 18 weeks. For Australian children, the case fatality rate of swine flu was no higher than for severe seasonal influenza. Because of the high number of children infected with swine flu, however, there were more children admitted to hospital than usual and more children died. Health‐care services (emergency departments, medical wards and intensive care units) were stretched. The introduction of special influenza clinics helped services cope. Pregnant women were at high risk of severe swine flu and seven pregnant women and seven of their babies died. Future pandemic planning should consider severity of influenza, in addition to rapidity of spread, as a criterion for escalating interventions.
Secretory leukocyte protease inhibitor inhibits neutrophil apoptosis
Authors: SUBRAMANIYAM Devipriya , HOLLANDER Camilla , WESTIN Ulla , ERJEFÄLT Jonas , STEVENS Tim , JANCIAUSKIENE Sabina
Published: November 2010

Background and objective:  The secretory leukocyte protease inhibitor (SLPI) is a major anti‐elastase barrier at the epithelial surfaces of upper respiratory tract. In addition to its anti‐protease activity, SLPI has been shown to express anti‐bacterial, anti‐viral and anti‐inflammatory properties.

Methods:  We measured SLPI concentration in nasal lavage fluid of healthy volunteers after challenge with endotoxin (LPS) and evaluated SLPI effects in vitro on neutrophil chemotaxis, adhesion, cytokine (IL‐8) release and apoptosis.

Results:  SLPI concentration in nasal lavage (n = 9) 2, 6 and 24 h after the challenge with LPS (25 µg) increased from 32% to 238% compared with baseline (226 ± 71 ng/mL). In vitro, SLPI (20–80 µg/mL) induced neutrophil chemotaxis (sixfold, P < 0.001) and decreased neutrophil apoptosis by 73% (P = 0.006), relative to controls. However, SLPI had no affect on IL‐8 release or neutrophil adhesion to fibronectin. SLPI‐positive immunoreactivity was co‐localized with neutrophils in lung specimens from patients with COPD.

Conclusions:  Our findings indicate upregulation of SLPI in response to LPS in nasal secretions and show anti‐apoptotic effects of SLPI in primary human neutrophils suggesting a new role of SLPI during neutrophilic inflammation.
Increased prevalence of primary drug‐resistant pulmonary tuberculosis in immunocompromised patients
Authors: JIANG Jung‐Rern , YEN Shiao‐Yu , WANG Jann‐Yuan
Published: November 2010

Background and objective:  Drug‐resistant tuberculosis (DR‐TB) is difficult and expensive to treat, and is associated with a higher rate of mortality. We conducted a long‐term survey to compare the prevalence of primary drug‐resistance, adverse effects of drugs and duration of treatment in immunocompetent and immunocompromised patients. Factors associated with primary drug resistance were also investigated.

Methods:  The patients studied had culture‐confirmed pulmonary TB but had not previously received anti‐TB treatment. These patients were divided into immunocompetent (IMCPe) and immunocompromised (IMCPr) groups. Baseline data, the prevalence of DR‐TB, duration of treatment and adverse effects of drugs were analysed. The rates of resistance to individual first‐line anti‐TB drugs in the two groups and in subgroups of the IMCPr group were calculated. Multinomial regression analysis was performed to investigate the risk factors associated with primary DR‐TB.

Results:  Among the 394 patients, 159 (40.4%) were in the IMCPr group. The baseline data for the two groups were similar, except that the IMCPr group was slightly older. The prevalence of drug‐resistance was higher in the IMCPr group (25.8% vs 17.0%, OR 1.69, 95% CI: 1.04–2.77), especially for isoniazid, rifampicin and streptomycin, and patients with liver cirrhosis, malignancies and those receiving immunosuppressants. The incidence of adverse drug effects was similar in the IMCPr and IMCPe groups. Multinomial regression analysis showed that being in the IMCPr group, and especially treatment with immunosuppressants, were independent risk factors for DR‐TB.

Conclusions:  Immunocompromised patients with underlying diseases had an increased prevalence of primary pulmonary DR‐TB but a similar incidence of drug‐related adverse effects. Diagnosis and investigation of drug‐resistance is important before initiating anti‐TB treatment in this group of patients.
Predicting factors of plural hospitalization with pneumonia in low‐birthweight infants
Authors: Torigoe Katsumi , Sasaki Sunao , Hoshina Jun , Torigoe Tsukasa , Hojo Moemi , Emura Shigehito , Kojima Kinuko , Onozuka Junya , Isobe Masatsugu , Numata Osamu
Published: November 2010

Background:  Children with a history of low birthweight (LBW) are often hospitalized with plural episodes of pneumonia after discharge from the neonatal intensive care unit. The aim of this study was to clarify the multiple factors predisposing them to developing three or more hospitalizations with pneumonia and whether the factors are related to their own prematurity. We also aimed to determine a predictable numerical formula for three or more episodes.

Methods:  Fourteen patients with two hospitalizations with pneumonia were grouped into group A. Fourteen patients with at least three episodes during the same investigation period were grouped into group B. The quantification theory type III was employed to investigate the similarities among the items and the gravity of each attribution in the two groups. To evaluate the items of discrimination of both groups, six items were analyzed by the quantification theory type II.

Results:  The dominant order of items contributing to the grouping was as follows: methicillin‐resistant staphylococcus aureus detection (partial correlation coefficient = 0.5284), asthmatic attack (partial correlation coefficient = 0.4138), severe motor and intellectual disability, Haemophilus influenzae, accompanying diseases and chronic lung disease. A predicting numerical formula was attained from these results. The success rate of discrimination was 85.7%. The six items seemed to be related to the patients' own prematurity.

Conclusions:  The authors emphasize that plural hospitalizations with pneumonia in the patients with LBW might be caused by the combined influence of six clinical factors as well as their own prematurity.