bluuebunny/crossref_metadata_2025 huggingface dataset:
Partitioning and mapping uncertainties in ensembles of forecasts of species turnover under climate change
Authors: Diniz‐Filho José Alexandre F. , Mauricio Bini Luis , Fernando Rangel Thiago , Loyola Rafael D. , Hof Christian , Nogués‐Bravo David , Araújo Miguel B.
Published: November 2009

Forecasts of species range shifts under climate change are fraught with uncertainties and ensemble forecasting may provide a framework to deal with such uncertainties. Here, a novel approach to partition the variance among modeled attributes, such as richness or turnover, and map sources of uncertainty in ensembles of forecasts is presented. We model the distributions of 3837 New World birds and project them into 2080. We then quantify and map the relative contribution of different sources of uncertainty from alternative methods for niche modeling, general circulation models (AOGCM), and emission scenarios. The greatest source of uncertainty in forecasts of species range shifts arises from using alternative methods for niche modeling, followed by AOGCM, and their interaction. Our results concur with previous studies that discovered that projections from alternative models can be extremely varied, but we provide a new analytical framework to examine uncertainties in models by quantifying their importance and mapping their patterns.
Can blood components with age‐related changes influence the ageing of endothelial cells?
Authors: Noh Ji Yeon , Oh Sang Ho , Lee Ju Hee , Kwon Yeon Sook , Ryu Dong Jin , Lee Kwang Hoon
Published: November 2009

Please cite this paper as:Can blood components with age‐related changes influence the ageing of endothelial cells? Experimental Dermatology 2009.

Abstract: Research on vascular endothelial cell ageing helps elucidate the pathogenesis of diseases associated with cell ageing. To investigate endothelial senescence, we used 2‐DE coupled with MS to perform a proteomic analysis of: (i) peripheral blood mononuclear cells (PBMCs) from donors in their 20 s (‘young’) or 60 s (‘old’) and (ii) human dermal microvascular endothelial cells (HDMECs) treated with sera from young and old donors. Identified proteins could be classified into several functional categories: (i) cytoskeletal regulators: CapG and cofilin 1; (ii) stress response and signal pathway proteins: TXNDC5 and RSU‐1; and (iii) apoptosis proteins: Annexin V. We confirmed by Western blot a decrease of RSU‐1, CapG and TXNDC5 in PBMCs from old donors. RSU‐1, which regulates signal transduction of the downstream Ras, showed decreased mRNA and protein levels in PBMCs from old donors and decreased mRNA levels in HDMECs treated with sera from old donors. In addition, Ras protein levels were increased in PBMCs from old donors. These data indicate that reduced RSU‐1 might induce Ras expression, which subsequently could provoke Ras‐induced senescence. In conclusion, our data suggest that blood components that exhibit age‐related changes, such as alterations in cytoskeletal regulators and stress proteins, may be associated with endothelial cell ageing.
Visualization of melatonin’s multiple mitochondrial levels of protection against mitochondrial Ca2+‐mediated permeability transition and beyond in rat brain astrocytes
Authors: Jou Mei‐Jie , Peng Tsung‐I , Hsu Lee‐Fen , Jou Shuo‐Bin , Reiter Russel J. , Yang Chuen‐Mao , Chiao Chuan‐Chin , Lin Yi‐Fan , Chen Chun‐Chia
Published: November 2009

Abstract: Melatonin protects cells against various types of oxidative stress‐induced apoptosis due primarily to its ability to effectively scavenge pathological and disease condition‐augmented generation of mitochondrial reactive oxygen species (mROS). Once produced, mROS indiscriminately damage mitochondrial components and more importantly they crucially activate directly the mitochondrial permeability transition (MPT), one of the critical mechanisms for initiating post mitochondrial apoptotic signaling. Whether or not melatonin targets directly the MPT, however, remains inconclusive, particularly during oxidative stress. This study, thus, investigated this possibility of an ‘oxidation free Ca2+stress’ in the presence of vitamin E after ionomycin exposure as a sole Ca2+‐mediated MPT in order to exclude melatonin’s primary antioxidative effects as well as Ca2+‐mediated oxidative stress. The studies were carried out using cultured rat brain astrocytes RBA‐1. With the application of laser scanning multiple fluorescence imaging microscopy, we visualized for the first time multiple mitochondrial protective effects provided by melatonin during Ca2+stress. First, melatonin, due to its primary antioxidative actions, completely prevented mCa2+‐induced mROS formation during ionomycin exposure. Secondly, when melatonin’s antioxidative effects were prevented due to the addition of vitamin E, melatonin significantly prevented mCa2+‐mediated MPT and apoptosis suggesting its direct targeting of the MPT. Surprisingly, in the presence of cyclosporin A, a MPT inhibitor, melatonin reduced further mCa2+‐mediated apoptosis during ionomycin exposure also suggesting its targeting beyond the MPT. As astrocytes are actively involve in regulating synaptic transmission and neurovascular coupling in the CNS, these multiple mitochondrial layers of protection provided by melatonin against mCa2+‐and/or mROS‐mediated apoptosis in astrocytes may be crucial for future therapeutic prevention and treatment of astrocyte‐mediated neurodegenerative diseases in the CNS.
Mucin‐type O‐glycosylation – putting the pieces together
Authors: Jensen Pia H. , Kolarich Daniel , Packer Nicolle H.
Published: November 2009

The O‐glycosylation of Ser and Thr by N‐acetylgalactosamine‐linked (mucin‐type) oligosaccharides is often overlooked in protein analysis. Three characteristics make O‐linked glycosylation more difficult to analyse than N‐linked glycosylation, namely: (a) no amino acid consensus sequence is known; (b) there is no universal enzyme for the release of O‐glycans from the protein backbone; and (c) the density and number of occupied sites may be very high. For significant biological conclusions to be drawn, the complete picture of O‐linked glycosylation on a protein needs to be determined. This review specifically addresses the analytical approaches that have been used, and the challenges remaining, in the characterization of both the composition and structure of mucin‐type O‐glycans, and the determination of the occupancy and heterogeneity at each amino acid attachment site.
Variability of Cloud‐free Ultraviolet Dose Rates on Global Scale Due to Modeled Scenarios of Future Ozone Recovery
Authors: Kazantzidis Andreas , Tourpali Kleareti , Bais Alkiviadis F.
Published: November 2009

Simulations of the total ozone content and vertical ozone and temperature profiles during the period 1980–2080 from three chemistry climate models (CCMs) were used and the future variability of five UV dose rate types in global scale was simulated. For each CCM, radiative transfer calculations for cloud‐free skies and constant values of aerosol optical properties and surface reflectivity were performed and the percentage difference, relative to the mean over the period 1996–2005, was calculated. The potential biological consequences of ozone recovery are quantified due to the different influence of ozone‐absorbing wavelengths on the selected UV action spectra: average percentage differences between a few and 60% are revealed during the 2070s, depending on the latitude zone and the season. Although the research into the prediction of UV radiation levels is ongoing, due to the possible future changes in cloudiness, aerosols or surface reflectivity, the long‐term changes in ozone, as projected by the CCMs in a similar way, will affect strongly some of the selected UV dose rates in the future.
Human neuroblastoma cell line SNU‐NB1 loses sensitivity to brain‐derived neurotrophic factor during establishment
Authors: Yun Woong Jae , Kim Soo Hee , Shin Eun , Jang Ja June , Lee Kyoungbun
Published: November 2009

Background and aims:The expression pattern of high affinity neurotrophin receptors dichotomizes the clinicopathologic characteristics of neuroblastoma (NB). The effects mediated by trkA have been documented in many experimental systems, whereas the effects mediated by trkB have only been investigated in limited studies.Methods:We established a new cell line of NB, “SNU‐NB1”, by primary culture and the effects mediated by trkB were addressed in this cell line.Results:NB cells in primary culture showed amplification of N‐myc and expression of trkB. Activation of trkB in primary culture by brain‐derived neurotrophic factor (BDNF) was followed by activation of extracellular signal‐regulated kinase1/2 (ERK1/2), growth inhibition, neuronal differentiation, and N‐myc down‐regulation. However, fully transformed SNU‐NB1 cells lost BDNF sensitivity while being tumorigenicin vivo. Restoration of trkB expression in SNU‐NB1 cells, by retroviral infection of trkB, induced differentiation and inhibition of growth in the cells following BDNF treatment. Although the prognosis of neuroblastomas is different according to the status of trkA and trkB mRNA expressions, the cytologic effects mediated by trkB per se are similar to those by trkA in NB.Conclusion:The patterns of trkA and trkB mRNA expression were markers for different lineages of transformed cells but were inconsistent with the clinical behavior.
Learning of content knowledge and development of scientific reasoning ability: A cross culture comparison
Authors: Bao Lei , Fang Kai , Cai Tianfang , Wang Jing , Yang Lijia , Cui Lili , Han Jing , Ding Lin , Luo Ying
Published: November 2009

We report the results of our study of the connections between students’ learning of physics content knowledge and the development of general scientific reasoning abilities. In particular, we seek to determine whether and to what extent content learning affects the development of general reasoning abilities. Pre-college-instruction data of first-year college students in the United States and China were collected using the FCI, BEMA, and Lawson’s classroom test of scientific reasoning. We find that the rigorous learning of physics knowledge in middle and high schools has made a significant impact on the ability of students in China to solve physics problems, but this knowledge does not seem to have a direct effect on their general scientific reasoning ability, which is determined to be at the same level as that of the students in the United States.
Interference with polarized light beams: Generation of spatially varying polarization
Authors: Rodríguez-Lara B. M. , Ricardez-Vargas I.
Published: November 2009

We propose a method based on a Mach–Zehnder interferometer to analyze the superposition of polarized laser beams at a given angle. The focus of our study is the spatially varying polarization state of the resulting field, also known as a polarization grating, generated by this setup. Our proposal combines a description of the resulting field in terms of its Stokes parameters with an experimental demonstration of the existence of such a polarization grating due to the effects of polarization on beam interference experiments.
Diagnosis and management of the limb girdle muscular dystrophies
Authors: Bushby Kate
Published: November 2009

Making the diagnosis of a particular type of limb girdle muscular dystrophy (LGMD) can appear challenging. In fact, various clues from the way the patient presents, and the results of simple investigations such as creatine kinase levels, can be extremely helpful in sorting out the various disease entities within this group of patients. The results of more specialised testing of the muscle biopsy and DNA sequencing offer the prospect of a clear answer in around 75% of cases. As more is understood about the clinical features of the different types of LGMD, targeted management is increasingly possible, especially focusing on those patients at high risk of cardiac and respiratory complications.
Late Cortical Disinhibition in Human Motor Cortex: A Triple-Pulse Transcranial Magnetic Stimulation Study
Authors: Cash R. F. H. , Ziemann U. , Murray K. , Thickbroom G. W.
Published: November 2009

In human motor cortex transcranial magnetic stimulation (TMS) has been used to identify short-interval intracortical inhibition (SICI) corresponding to γ-aminobutyric acid type A (GABAA) effects and long-interval intracortical inhibition (LICI) and the cortical silent period (SP) corresponding to postsynaptic GABAB effects. Presynaptic GABAB effects, corresponding to disinhibition, can also be identified with TMS and have been shown to be acting during LICI by measuring SICI after a suprathreshold priming stimulus (PS). The duration of disinhibition is not certain and, guided by studies in experimental preparations, we hypothesized that it may be longer-lasting than postsynaptic inhibition, leading to a period of late cortical disinhibition and consequently a net increase in corticospinal excitability. We tested this first by measuring the motor-evoked potential (MEP) to a test stimulus (TS), delivered after a PS at interpulse intervals (IPIs) ≤300 ms that encompassed the period of PS-induced LICI and its aftermath. MEP amplitude was initially decreased, but then increased at IPIs of 190–210 ms, reaching 160 ± 17% of baseline 200 ms after PS ( P < 0.05). SP duration was 181 ± 5 ms. A second experiment established that the onset of the later period of increased excitability correlated with PS intensity ( r2 = 0.99) and with the duration of the SP ( r2 = 0.99). The third and main experiment demonstrated that SICI was significantly reduced in strength at all IPIs ≤220 ms after PS. We conclude that TMS-induced LICI is associated with a period of disinhibition that is at first masked by LICI, but that outlasts LICI and gives rise to a period during which disinhibition predominates and net excitability is raised. Identification of this late period of disinhibition in human motor cortex may provide an opportunity to explore or modulate the behavior of excitatory networks at a time when inhibitory effects are restrained.
Treatment of Chronic Hepatitis C in a Patient Affected by Systemic Sclerosis
Authors: Poggi Guido , Villani Laura , Sottotetti Federico , Tagliaferri Barbara , Montagna Benedetta , Amatu Alessio , Bernardo Giovanni
Published: November 2009

The currently recommended treatment for patients infected with hepatitis C virus (HCV) is pegilated interferon α (IFN α) plus ribavirin. Despite the numerous benefits of this therapy, there is an increasing concern regarding his tolerance. Among the most common side effects, interferon may trigger the onset or exacerbation of autoimmune diseases. When chronic hepatitis C coexists with an autoimmune disorder, it is not clear whether using interferon is better than avoiding it. We evaluated the disease state of a 55-year old female affected by sistemic sclerosis (SSc), during and after therapy with IFNα pegilated plus ribavirin for chronic HCV infection. We were worried about the potential worsening of the autoimmune disease during the therapy, but we were confident that we would give our patient a short course of peginterferon and ribavirin. A mild, asymptomatic worsening of lung SSc was observed during IFN administration, without life threatening symptoms. After 24 months follow up we observed the maintenance of the virological response and a good control of the rheumatological disease. Thus, in liver disease at high risk of progression and concomitant SSc, the antiviral therapy with IFNα is a feasible approach.
A Novel Paradigm to Trigger Apoptosis in Chronic Lymphocytic Leukemia
Authors: Loeder Sandra , Zenz Thorsten , Schnaiter Andrea , Mertens Daniel , Winkler Dirk , Döhner Hartmut , Debatin Klaus-Michael , Stilgenbauer Stephan , Fulda Simone
Published: November 2009

Evasion of apoptosis is a hallmark of chronic lymphocytic leukemia (CLL), calling for new strategies to bypass resistance. Here, we provide first evidence that small-molecule X-linked inhibitor of apoptosis (XIAP) inhibitors in combination with the death receptor ligand tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) present a novel approach to trigger apoptosis in CLL, including subgroups with resistant disease or unfavorable prognosis. XIAP, cellular IAP (cIAP) 1, and cIAP2 are expressed at high levels in primary CLL samples. Proof-of-concept studies in CLL cell lines show that subtoxic concentrations of XIAP inhibitors significantly enhance TRAIL-induced apoptosis and also sensitize for CD95-mediated apoptosis. Importantly also in primary CLL samples, XIAP inhibitor acts in concert with TRAIL to trigger apoptosis in 18 of 27 (67%) cases. This XIAP inhibitor–induced and TRAIL-induced apoptosis involves caspase-3 activation and is blocked by the caspase inhibitor zVAD.fmk. The cooperative interaction of XIAP inhibitor and TRAIL is even evident in distinct subgroups of patients with poor prognostic features (i.e., with 17p deletion, TP53 mutation, chemotherapy-refractory disease, or unmutated VH genes). Interestingly, cases with unmutated VH genes were significantly more sensitive to XIAP inhibitor–induced and TRAIL-induced apoptosis compared with VH gene–mutated samples, pointing to a role of B-cell receptor signaling in apoptosis regulation. By showing that XIAP inhibitors in combination with TRAIL present a new strategy to trigger apoptosis even in resistant forms and poor prognostic subgroups of CLL, our findings have important implications for the development of apoptosis-based therapies in CLL. [Cancer Res 2009;69(23):8977–86]
Inositol Hexaphosphate Suppresses Growth and Induces Apoptosis in Prostate Carcinoma Cells in Culture and Nude Mouse Xenograft: PI3K-Akt Pathway as Potential Target
Authors: Gu Mallikarjuna , Roy Srirupa , Raina Komal , Agarwal Chapla , Agarwal Rajesh
Published: November 2009

Constitutive activation of phosphoinositide 3-kinase (PI3K)-Akt pathway transmits growth-regulatory signals that play a central role in promoting survival, proliferation, and angiogenesis in human prostate cancer cells. Here, we assessed the efficacy of inositol hexaphosphate (IP6) against invasive human prostate cancer PC-3 and C4-2B cells and regulation of PI3K-Akt pathway. IP6 treatment of cells suppressed proliferation, induced apoptosis along with caspase-3 and poly(ADP-ribose) polymerase (PARP) cleavage, and inhibited constitutive activation of Akt and its upstream regulators PI3K, phosphoinositide-dependent kinase-1 and integrin-linked kinase-1 (ILK1). Downstream of Akt, IP6 inhibited the phosphorylation of glycogen synthase kinase-3α/β at Ser21/9 and consequently reduced cyclin D1 expression. Efficacy studies employing PC-3 tumor xenograft growth in nude mice showed that 2% (w/v) IP6 feeding in drinking water inhibits tumor growth and weight by 52% to 59% (P < 0.001). Immunohistochemical analysis of xenografts showed that IP6 significantly reduces the expression of molecules associated with cell survival/proliferation (ILK1, phosphorylated Akt, cyclin D1, and proliferating cell nuclear antigen) and angiogenesis (platelet endothelial cell adhesion molecule-1 or CD31, vascular endothelial growth factor, endothelial nitric oxide synthase, and hypoxia-inducible factor-1α) together with an increase in apoptotic markers (cleaved caspase-3 and PARP). These findings suggest that, by targeting the PI3K-ILK1-Akt pathway, IP6 suppresses cell survival, proliferation, and angiogenesis but induces death in prostate cancer cells, which might have translational potential in preventing and controlling the growth of advanced and aggressive prostate cancer for which conventional chemotherapy is not effective. [Cancer Res 2009;69(24):9465–72]
L1 Cell Adhesion Molecule Is a Novel Independent Poor Prognostic Factor of Extrahepatic Cholangiocarcinoma
Authors: Li Shengjin , Jo Young Suk , Lee Jae-Hyek , Min Jeong-Ki , Lee Eung Seuk , Park Taewoo , Kim Jin-Man , Hong Hyo Jeong
Published: November 2009

Purpose: Cholangiocarcinomas (CC) are associated with poor survival, but diagnostic markers and therapeutic targets have not yet been elucidated. We previously found aberrant expression of L1 cell adhesion molecule in intrahepatic CC and a role for L1 in the progression of intrahepatic CC. Here, we analyzed L1 expression in extrahepatic CC (ECC) and evaluated its prognostic significance.

Experimental Design: We examined L1 expression in tumors from 75 ECC patients by immunohistochemistry. We analyzed the correlations between L1 expression and clinicopathologic factors as well as patient survival.

Results: L1 was not expressed in normal extrahepatic bile duct epithelium but was aberrantly expressed in 42.7% of ECC tumors. High expression of L1 was detected at the invasive front of tumors and was significantly associated with perineural invasion (P < 0.01). Univariate analysis indicated that various prognostic factors such as histologic grade 3, advanced pathologic T stage and clinical stage, perineural invasion, nodal metastasis, and high expression of L1 were risk factors predicting patient survival. Multivariate analyses done by Cox's proportional hazards model showed that high expression of L1 (hazard ratio, 2.171; 95% confidence interval, 1.162-4.055; P = 0.015) and nodal metastasis (hazard ratio, 2.088; 95% confidence interval, 1.159-3.764; P = 0.014) were independent risk factors for patient death.

Conclusions: L1 was highly expressed in 42.7% of ECC and its expression was significantly associated with perineural invasion. High expression of L1 and nodal metastasis were independent poor prognostic factors predicting overall survival in patients with ECC. (Clin Cancer Res 2009;15(23):7345–51)
Pharmacologically Increased Tumor Hypoxia Can Be Measured by 18F-Fluoroazomycin Arabinoside Positron Emission Tomography and Enhances Tumor Response to Hypoxic Cytotoxin PR-104
Authors: Cairns Rob A. , Bennewith Kevin L. , Graves Edward E. , Giaccia Amato J. , Chang Daniel T. , Denko Nicholas C.
Published: November 2009

Purpose: Solid tumors contain microenvironmental regions of hypoxia that present a barrier to traditional radiotherapy and chemotherapy, and this work describes a novel approach to circumvent hypoxia. We propose to overcome hypoxia by augmenting the effectiveness of drugs that are designed to specifically kill hypoxic tumor cells.

Experimental Design: We have constructed RKO colorectal tumor cells that express a small RNA hairpin that specifically knocks down the hypoxia-inducible factor 1a (HIF1a) transcription factor. We have used these cells in vitro to determine the effect of HIF1 on cellular sensitivity to the hypoxic cytotoxin PR-104, and its role in cellular oxygen consumption in response to the pyruvate dehydrogenase kinase inhibitor dichloroacetate (DCA). We have further used these cells in vivo in xenografted tumors to determine the role of HIF1 in regulating tumor hypoxia in response to DCA using 18F-fluoroazomycin arabinoside positron emission tomography, and its role in regulating tumor sensitivity to the combination of DCA and PR-104.

Results: HIF1 does not affect cellular sensitivity to PR-104 in vitro. DCA transiently increases cellular oxygen consumption in vitro and increases the extent of tumor hypoxia in vivo as measured with 18F-fluoroazomycin arabinoside positron emission tomography. Furthermore, we show that DCA-dependent alterations in hypoxia increase the antitumor activity of the next-generation hypoxic cytotoxin PR-104.

Conclusions: DCA interferes with the HIF-dependent “adaptive response,” which limits mitochondrial oxygen consumption. This approach transiently increases tumor hypoxia and represents an important method to improve antitumor efficacy of hypoxia-targeted agents, without increasing toxicity to oxygenated normal tissue. (Clin Cancer Res 2009;15(23):7170–4)
Therapeutic Potential of Adult Bone Marrow–Derived Mesenchymal Stem Cells in Prostate Cancer Bone Metastasis
Authors: Chanda Diptiman , Isayeva Tatyana , Kumar Sanjay , Hensel Jonathan A. , Sawant Anandi , Ramaswamy Girish , Siegal Gene P. , Beatty Matthew S. , Ponnazhagan Selvarangan
Published: November 2009

Purpose: Current evidence indicates that an osteoblast lesion in prostate cancer is preceded by osteolysis. Thus, prevention of osteolysis would reduce complications of bone metastasis. Bone marrow–derived mesenchymal stem cells have the ability to differentiate into osteoblast and produce osteoprotegerin, a decoy receptor for the receptor activator for nuclear factor κB ligand, naturally. The present study examined the potential of unmodified mesenchymal stem cells to prevent osteolytic bone lesions in a preclinical mouse model of prostate cancer.

Experimental Design: The human prostate cancer cell line PC3 was implanted in tibiae of severe combined immunodeficient mice. After establishment of the tumor, either unmodified or genetically engineered mesenchymal stem cells overexpressing osteoprotegerin was injected at the site of tumor growth. The effects of therapy were monitored by bioluminescence imaging, micro–computed tomography, immunohistochemistry, and histomorphometry.

Results: Data indicated significant (P < 0.001) inhibition of tumor growth and restoration of bone in mice treated with unmodified and modified mesenchymal stem cells. Detailed analysis suggested that the donor mesenchymal stem cell inhibited tumor progression by producing woven bone around the growing tumor cells in the tibiae and by preventing osteoclastogenesis.

Conclusions: Overcoming the limitation of the number of mesenchymal stem cells available in the bone can provide significant amelioration for osteolytic damage without further modification. (Clin Cancer Res 2009;15(23):7175–85)
Intravenous Immunoglobulin Reduces Infarct Volume but Not Edema Formation in Acute Stroke
Authors: Walberer Maureen , Nedelmann Max , Ritschel Nouha , Mueller Clemens , Tschernatsch Marlene , Stolz Erwin , Bachmann Georg , Blaes Franz , Gerriets Tibo
Published: November 2009

Objectives: Intravenous immunoglobulin (IVIG) is used for treatment of immunodeficiencies and autoimmune disorders. Recently, IVIG has also been shown to reduce infarct size in acute stroke. Since edema treatment can provide secondary neuroprotective effects, we conducted the present study to evaluate whether edema reduction is the underlying cause of the neuroprotective properties of IVIG in experimental stroke. Methods: Male Wistar rats received either IVIG or placebo and were subjected to temporary middle cerebral artery occlusion. 24 h after temporary middle cerebral artery occlusion, clinical evaluation and 7.0T magnetic resonance imaging were performed. Ischemic lesion volume was determined on high-resolution T2 images. T2 relaxation time and midline shift assessed on magnetic resonance imaging as well as brain water content detected by the wet/dry method after 24 h were measured to quantify edema formation. Results: Pretreatment with IVIG leads to a statistically significant reduction of the ischemic lesion volume by 42% after 24 h, as compared to placebo treatment (p < 0.05). All three methods for quantifying edema formation indicated no differences between IVIG-treated and untreated animals (p > 0.05). Conclusion: These results suggest that the neuroprotective effect of IVIG is not an indirect result of edema reduction, but is caused by direct neuronal protection. Application of IVIG is a promising treatment concept for acute stroke. To further investigate this neuroprotective effect, studies on the efficacy, the safety profile and on the underlying mechanisms are required.
Superimposed Segmental Hemangioma of Infancy
Authors: Happle Rudolf
Published: November 2009

Background: Segmental hemangioma of infancy is sometimes associated with the development of multiple nonsegmental hemangiomas. Such co-occurrences have so far remained unexplained. Methods and Results: Pertinent reports were collected from the literature. To explicate such cases, the following concept is proposed. Hemangiomas of infancy reflect a polygenic predisposition. Nonsegmental lesions result from a mutational event occurring at a late stage of intrauterine life or after birth, whereas segmental hemangioma originates from loss of heterozygosity or some other mutational event arising at an early developmental stage. Conclusion: In this way, segmental hemangioma of infancy could be taken as a further example of the superimposed segmental manifestation of a polygenic skin disorder. Future molecular research may show whether this assumption holds true.
Surgical Transpositioning of Ectopic Ovarian Tissue and Pregnancy
Authors: Halil Sait , Kucuk Mert , Çepni İsmail
Published: November 2009

Objective: Our objective was to report transpositioning an ectopic ovary, successfully using the assisted reproduction technique (ART), with the outcome of retrieving an oocyte from the transpositioned ovary during ART. Case Report: The couple, presenting with a history of 2 years of secondary infertility, was admitted to our hospital. Two years earlier, the patient had undergone a left salpingo-oophorectomy for a ruptured ectopic pregnancy. The right ovary had not been detected during the previous operation. During surgery, we observed that the right ovary was attached to the posterior abdominal wall near the hepatic flexura. It was repositioned, moved, placed and fixed to the posterior wall of the uterus. One follicle developed and was retrieved from the transpositioned ovary during in vitro fertilization. The patient now has a healthy ongoing singleton pregnancy. Conclusion: An ectopic ovary is an extremely rare gynecological entity. Transpositioning an ectopic ovary should be kept in mind as a possible procedure for the management of patients presenting with infertility where the other ovary is absent or does not respond to controlled ovarian hyperstimulation treatment.
Prospective Evaluation of Waist Circumference and Visceral Adipose Tissue in Patients with Chronic Kidney Disease
Authors: Velludo Claudia M.O. , Kamimura Maria A. , Sanches Fabiana M.R. , Lemos Marcelo M. , Canziani Maria Eugênia F. , Pupim Lara B. , Draibe Sérgio A. , Cuppari Lilian
Published: November 2009

Background: Waist circumference (WC), a simple anthropometric measure, is associated with visceral adipose tissue (VAT) in cross-sectional studies, and thus has been used as a surrogate marker for VAT. However, associations between changes over time in WC and VAT have not been studied in chronic kidney disease (CKD) patients. Methods: This prospective study included 87 nondialysis-dependent CKD patients (54 males, 56.2 ± 10.4 years, BMI 27.3 ± 5.1, GFR 35.9 ± 14.6 ml/min/1.73 m2). VAT area was measured by computed tomography (CT) and WC was measured at the umbilicus level at baseline and after 12 months. Results: Changes in WC correlated significantly but weakly with changes in VAT (r = 0.26, p = 0.016), likely due to a substantially smaller change in WC compared to changes in VAT. This was also reflected by a kappa coefficient of 0.26, i.e. indicative of poor agreement between WC and CT measurements in regards to quantification of changes in VAT. Likewise, the receiver operating characteristic curve analysis identified WC as poor predictor of changes in VAT (area under the curve = 0.62). Conclusion: Anthropometric measurement of WC is poorly correlated with changes in VAT measured by CT in nondialysis-dependent CKD patients. Therefore, caution should be taken when using WC as a surrogate marker of VAT changes in this population.
Modulation of Mitochondrial Proteome and Improved Mitochondrial Function by Biventricular Pacing of Dyssynchronous Failing Hearts
Authors: Agnetti Giulio , Kaludercic Nina , Kane Lesley A. , Elliott Steven T. , Guo Yurong , Chakir Khalid , Samantapudi Daya , Paolocci Nazareno , Tomaselli Gordon F. , Kass David A. , Van Eyk Jennifer E.
Published: November 2009

Background—

Cardiac resynchronization therapy (CRT) improves chamber mechanoenergetics and morbidity and mortality of patients manifesting heart failure with ventricular dyssynchrony; however, little is known about the molecular changes underlying CRT benefits. We hypothesized that mitochondria may play an important role because of their involvement in energy production.

Methods and Results—

Mitochondria isolated from the left ventricle in a canine model of dyssynchronous or resynchronized (CRT) heart failure were analyzed by a classical, gel-based, proteomic approach. Two-dimensional gel electrophoresis revealed that 31 mitochondrial proteins where changed when controlling the false discovery rate at 30%. Key enzymes in anaplerotic pathways, such as pyruvate carboxylation and branched-chain amino acid oxidation, were increased. These concerted changes, along with others, suggested that CRT may increase the pool of Krebs cycle intermediates and fuel oxidative phosphorylation. Nearly 50% of observed changes pertained to subunits of the respiratory chain. ATP synthase-β subunit of complex V was less degraded, and its phosphorylation modulated by CRT was associated with increased formation (2-fold,
P
=0.004) and specific activity (+20%,
P
=0.05) of the mature complex. The importance of these modifications was supported by coordinated changes in mitochondrial chaperones and proteases. CRT increased the mitochondrial respiratory control index with tightened coupling when isolated mitochondria were reexposed to substrates for both complex I (glutamate and malate) and complex II (succinate), an effect likely related to ATP synthase subunit modifications and complex quantity and activity.

Conclusions—

CRT potently affects both the mitochondrial proteome and the performance associated with improved cardiac function.
Relationship Between Regional Myocardial Oxygenation and Perfusion in Patients With Coronary Artery Disease
Authors: Karamitsos Theodoros D. , Leccisotti Lucia , Arnold Jayanth R. , Recio-Mayoral Alejandro , Bhamra-Ariza Paul , Howells Ruairidh K. , Searle Nick , Robson Matthew D. , Rimoldi Ornella E. , Camici Paolo G. , Neubauer Stefan , Selvanayagam Joseph B.
Published: November 2009

Background—

It is recognized that the interplay between myocardial ischemia, perfusion, and oxygenation in the setting of coronary artery disease (CAD) is complex and that myocardial oxygenation and perfusion may become dissociated. Blood oxygen level–dependent (BOLD) cardiovascular magnetic resonance (CMR) has the potential to noninvasively measure myocardial oxygenation, whereas positron emission tomography (PET) with oxygen-15 labeled water is the gold standard technique for myocardial blood flow quantification. Thus, we sought to apply BOLD CMR at 3 T and oxygen-15–labeled water PET in patients with CAD and normal volunteers to better understand the relationship between regional myocardial oxygenation and blood flow during vasodilator stress.

Methods and Results—

Twenty-two patients (age, 62�8 years; 16 men) with CAD (at least 1 stenosis ≥50% on quantitative coronary angiography) and 10 normal volunteers (age, 58�6 years; 6 men) underwent 3-T BOLD CMR and PET. For BOLD CMR, 4 to 6 midventricular short-axis images were acquired at rest and during adenosine stress (140 μg/kg/min). Using PET with oxygen-15–labeled water, myocardial blood flow was measured at baseline and during adenosine in the same slices. BOLD images were divided into 6 segments, and mean signal intensities calculated. Taking ≥50% stenosis on quantitative coronary angiography as the gold standard, cutoff values for stress myocardial blood flow (<2.45 mL/min/g; AUC, 0.83) and BOLD signal intensity change (<3.74%; AUC, 0.78) were determined to define ischemic segments. BOLD CMR and PET agreed on the presence or absence of ischemia in 18 of the 22 patients (82%) and in all normal subjects. On a per-segment analysis, 40% of myocardial segments with stress myocardial blood flow below the cutoff of 2.45 mL/min/g did not show deoxygenation, whereas 88% of segments with normal perfusion also had normal oxygenation measurements.

Conclusions—

Regional myocardial perfusion and oxygenation may be dissociated, indicating that in patients with CAD, reduced perfusion does not always lead to deoxygenation.
Relationship Between Baseline Inflammatory Markers, Antiplatelet Therapy, and Adverse Cardiac Events After Percutaneous Coronary Intervention
Authors: Dosh Kristofer , Berger Peter B. , Marso Steven , van Lente Fredrick , Brennan Danielle M. , Charnigo Richard , Topol Eric J. , Steinhubl Steven
Published: November 2009

Background—

We evaluated patients undergoing percutaneous coronary intervention to assess the predictive value of high-sensitivity C-reactive protein (hs-CRP) and pregnancy-associated plasma protein-A (PAPP-A) on adverse cardiac outcomes and the effect of antiplatelet therapy on these outcomes.

Methods and Results—

Baseline blood samples were available on 1468 CREDO (Clopidogrel for the Reduction of Events During Observation) patients for hs-CRP testing and 1096 patients for PAPP-A testing. The 1-year primary end point was the composite incidence of death, myocardial infarction, or stroke. Patients in the highest 2 tertiles of hs-CRP had more events compared with the lowest tertile (11.4% versus 6.4%,
P
=0.003). Treatment with clopidogrel reduced the 1-year composite end point for patients in the highest 2 tertiles of hs-CRP (9.1% clopidogrel versus 13.5% placebo,
P
=0.04) but not in the lowest tertile. Elevated PAPP-A levels were associated with a trend toward more events at 1 year that did not reach statistical significance. Patients in the highest 2 tertiles of PAPP-A randomized to clopidogrel had fewer events (7.3% clopidogrel versus 13.1% placebo,
P
=0.01), but no benefit was seen in the lowest tertile. A 46% risk reduction with randomization to clopidogrel was seen in patients in the highest 2 tertiles of both biomarkers (8.7% versus 16.2%,
P
=0.02).

Conclusions—

Patients undergoing nonurgent percutaneous coronary intervention who have elevated hs-CRP and PAPP-A have an increased incidence of adverse cardiovascular events. The clinical benefit of adding clopidogrel to aspirin seems greater in those with increased levels of these inflammatory biomarkers.
Three Ibrāhīms: Literary Production and the Remaking of the Tijāniyya Sufi Order in Twentieth-Century Sudanic Africa
Authors: Seesemann Rüdiger
Published: November 2009

In terms of the number of followers, the Tijāniyya is the largest Sufi order in sub-Saharan Africa. Geographically, it is strongest in West Africa, but also plays a significant role in the Maghreb and Eastern Sudanic Africa. This article highlights the development of the Tijāniyya in three locations during the twentieth century by focusing on three of its leading figures, who all happen to be called Ibrāhīm: Ibrāhām Niasse (1900-1975) from Kaolack (Senegal), sharīf Ibrāhīm Sālih (born 1939) from Maiduguri (Nigeria), and sharīf Ibrāhīm Sīdī (1949-1999) from El Fasher (Sudan). Through a comparative analysis of their biographies and some of their writings, the paper shows how these three personalities were instrumental in adapting Tijānī doctrines and practices to changing contexts and circumstances that reflect both local conditions and global influences. The study is based on extensive fieldwork conducted by the author over an extended period of time and proposes to view Sufi communities as dynamic entities, rather than static expressions of “traditional Islam”, in order to explain the continuing relevance of Sufism in African Muslim societies. As the paper demonstrates, the process of remaking the Tijāniyya can lead to rather contradictory results.
Administration of Justice in the World Trade Organization: Did the WTO Appellate Body Commit 'Grave Injustice'?
Authors: Petersmann Ernst-Ulrich
Published: November 2009

Judicial administration of justice through reasoned interpretation, application and clarification of legal principles and rules is among the oldest paradigms of 'constitutional justice'. The principles of procedural justice underlying WTO dispute settlement procedures, like the conformity of WTO dispute settlement rulings with principles of 'substantive justice', remain controversial. This contribution criticizes the recent, harsh condemnation of the WTO dispute settlement rulings in the Brazil Tyres case as 'committing grave injustice'. After recalling the customary law requirement of interpreting treaties and settling international disputes 'in conformity with principles of justice' and human rights, the contribution examines the WTO Appellate Body case-law from the perspective of diverse conceptions of 'conservative' and 'reformative justice', 'general' and 'particular justice', procedural and substantive justice, national and multilevel 'constitutional justice', and judicial protection of transnational rule-of-law for the benefit of citizens. The article concludes that the panel, appellate and arbitration reports in the Brazil Tyres dispute, like many other WTO Appellate Body reports, reflect a growing concern 'to administer justice' in WTO dispute settlement proceedings. WTO judges and investor-state arbitrators should follow the example of the ICJ and of European courts and clarify the 'principles of justice' justifying their settlement of international economic disputes so that 'justice is not only done, but also seen to be done', albeit subject to 'trial and error'. Legal practitioners should support – and, as part of the 'invisible college of international lawyers', hold accountable – the emergence of an 'international judiciary' as an 'epistemic community' committed to defending rule of law, peaceful settlement of disputes and 'principles of justice' in mutually beneficial economic cooperation among citizens across national frontiers.
Linking Home-School Dissonance to School-Based Outcomes for African American High School Students
Authors: Tyler Kenneth , Brown-Wright Lynda , Stevens-Watkins Danelle , Thomas Deneia , Stevens Ruby , Roan-Belle Clarissa , Gadson Nadia , Smith La Toya
Published: November 2009

The current study examined associations between home-school dissonance and several academic and psychological variables among 239 African American high school students. Regression analyses revealed that home-school dissonance significantly predicted multiple academic and psychological variables, including academic cheating, disruptive classroom behavior, performance avoidant and performance approach goal orientations, and poor self-reported English and math grades. Implications of this research include a more systematic incorporation of African American high school students’ out-of-school experiences into their classroom learning experiences.
Radiocarbon chronology of Holocene colluvial (debris-flow) events at Sletthamn, Jotunheimen, southern Norway: a window on the changing frequency of extreme climatic events and their landscape impact
Authors: Matthews John A. , Dahl Svein Olaf , Dresser P. Quentin , Berrisford Mark S. , Lie Øyvind , Nesje Atle , Owen Geraint
Published: November 2009

The history of colluvial events over the last 8500 years is reconstructed in three Norwegian alpine slope-foot mires fed by three independent debris-flow systems. Chronologies for each site are constructed based on 155 radiocarbon-dated peat samples. At the multimillennial scale, debris-flow activity was greatest during the transition from the Holocene Thermal Maximum to the late Holocene ( c. 4300—2800 cal. BP) when debris-flow events occurred with a frequency of 1 in 33 years: two peaks in activity, characterized by 1 event in 14 years and 1 event in 25 years, were reached at the beginning and end of this interval, respectively. Least activity occurred during the Holocene Thermal Maximum from c. 8000 to 7100 cal. BP, with one event in 900 years. Eight distinct century- to millennial-scale phases of high debris-flow frequency (>3 events per 100 years) are identified at c. 8300—8000, 7100—7000, 4300—3700, 3200—2800, 2200—1900, 1500—1200, 800—700 and 300—0 cal. BP. Similarities in the records from the three sites suggest underlying climatic variations linked to the frequency of intense summer and autumn rainfall events (the primary meteorological trigger of slope failure in the source areas). Differences between the records reflect local site sensitivity to the initiation of debris-flow activity and the triggering of each subsequent debris-flow event. It is also inferred that each debris-flow system passes through multimillennial stages of at first increasing and later decreasing sensitivity as its source area expands. The climatic signals in the debris-flow record appear to differ in various respects from those derived from other precipitation-sensitive proxies from southern Norway (river floods, snow avalanches and glacier variations). Debris-flow records provide, therefore, complementary information relating to extreme climatic events and demonstrate instabilities in the Holocene landscape but provide little or no support for the concept of an increasing landscape impact of debris flows in response to global warming.
Impact of river capture on hydrography and water resources: case study of Ula and Katra catchments, south Lithuania
Authors: Linkevičiene Rita
Published: November 2009

Based on cartographic material from three time periods during the nineteenth and twentieth centuries, the impact of river capture, which started in the middle of the nineteenth century, on transformations of the watershed and hydrographic network of two Lithuanian rivers, Ula and Katra, is analysed. It has been determined that river capture conditioned marked transformations of water supply and distribution. As a result of the capture, the area of Ula catchment has increased by 62% and its mean discharge by 63%, whereas the area of Katra catchment decreased by 23% and its mean discharge by 27%. The total area of the five largest lakes in the recent Ula catchment has been reduced by 95%. The transformations of water resources in the Ula catchment since the first half of the nineteenth century are the following: Ula runoff volume has increased almost by 100 million m3/yr whereas the water volume of lakes has been reduced by almost 30 million m3.
Modern pollen—vegetation relationships along an altitudinal transect in the central Pyrenees (southwestern Europe)
Authors: Cañellas-Boltà Núria , Rull Valentí , Vigo Josep , Mercadé Arnau
Published: November 2009

Modern proxy-calibration studies are a powerful tool for paleoecological interpretation. This paper analyzes the relationships among modern pollen rain, vegetation and altitude in the central Pyrenees, where several paleo-palynological studies have been developed, but a modern analog survey is still unavailable. The work analyzes the pollen content of moss polsters from different vegetation communities along an altitudinal transect, as well as the flora and vegetation using the Braun-Blanquet system. DCCA showed that altitude satisfactorily explains both vegetation ( r2 = 0.988) and pollen ( r 2 = 0.841) gradients. Besides the complexity of pollen—vegetation relationships, some regularities were found to be useful for paleoecological and paleoenvironmental interpretation. In general, altitudinal vegetation and pollen patterns show similarities, but pollen belts and boundaries are less well defined, likely because of the homogenizing effect of upward wind transport. Palynological differentiation of montane from subalpine/alpine belts is straightforward from the trends of the more significant pollen types, mainly the low-altitude deciduous trees and the high-mountain herbs. Palynological differences between subalpine and alpine belts, which boundary coincides with the treeline, are more subtle and need quantitative criteria and complementary proxies. From an individual point of view, four main groups of pollen were distinguished, in relation to their usefulness as vegetation and altitudinal indicators: (1) very good indicators, (2) good indicators, (3) non indicators, and (4) allochthonous pollen types. The first two groups resulted to be useful as indicator taxa for modern analogs for paleovegetational and paleoaltitudinal reconstruction, while the latter two groups should be interpreted with caution in paleoenvironmental studies.