bluuebunny/crossref_metadata_2025 huggingface dataset:
Within-stand variation in understorey vegetation affects fire behaviour in longleaf pine xeric sandhills
Authors: Wenk Evelyn S. , Wang G. Geoff , Walker Joan L.
Published: October 2011

The frequent fires typical of the longleaf pine ecosystem in the south-eastern USA are carried by live understorey vegetation and pine litter. Mature longleaf pine stands in the xeric sandhills region have a variable understorey vegetation layer, creating several fuel complexes at the within-stand scale (20 m2). We identified three fuel complexes found in frequently burned stands on the Carolina Sandhills National Wildlife Refuge, and used prescribed fire to test whether distinct sets of fire conditions were associated with each fuel complex. Study plots were dominated by either turkey oak or wiregrass in the understorey, or lacked understorey vegetation and contained only longleaf pine litter. Turkey oak-dominated plots had the highest fuel loads, and during burns they had higher total net heat flux than wiregrass- or longleaf pine litter-dominated plots, and longer burn durations than wiregrass-dominated plots. Across all plots, the quantity of litter fragments had the greatest effect on fire temperature and duration of burn. These results show that the patchy understorey vegetation within longleaf pine stands will create heterogeneous fires, and areas dominated by turkey oak may have increased fire intensity and soil heating compared with the other two fuel complexes.
Capsular polysaccharide vaccine for Group BNeisseria meningitidis,Escherichia coliK1, andPasteurella haemolyticaA2
Authors: Robbins John B. , Schneerson Rachel , Xie Guilin , Hanson Lars Å. , Miller Mark A.
Published: October 2011

We reviewed the literature that is the basis for our proposal that (2→8)-α-Neu5Ac conjugates will be safe and effective vaccines for Group B meningococci (GBMs),Escherichia coliK1, andPasteurella haemolyticaA2. Although (2→8)-α-Neu5Ac is a virulence factor and a protective antigen of these three pathogens, it is also a component of normal tissues (neural cell adhesion molecule). Natural, anti–(2→8)-α-Neu5Ac present in most adults, vaccine-induced antibodies, and even high levels of spontaneously appearing monoclonal anti–(2→8)-α-Neu5Ac did not cause autoimmunity. Although it is not possible to prove a null hypothesis, there are no epidemiologic, serologic, immunologic, or clinical data to indicate that (2→8)-α-Neu5Ac antibodies will induce pathology or an autoimmune disease. No increased pathology caused by these antibodies was found, even in neonates and infants of mothers recovered from GBM meningitis. The lack of pathology mediated by anti–(2→8)-α-Neu5Ac may be explained by different presentations of (2→8)-α-Neu5Ac on bacterial and mammalian cells and by the unusual physicochemical properties of anti–(2→8)-α-Neu5Ac. Based on clinical and experimental data collected over 30 y and because (2→8)-α-Neu5Ac is an essential virulence factor and a protective antigen for GBM,E. coliK1, andP. haemolyticaA2, protein conjugates of it are easy to prepare using inexpensive and plentiful ingredients, and they would be compatible with routinely administered infant vaccines, clinical studies of these conjugates should proceed.
Control of skin cancer by the circadian rhythm
Authors: Gaddameedhi Shobhan , Selby Christopher P. , Kaufmann William K. , Smart Robert C. , Sancar Aziz
Published: October 2011

Skin cancer is the most common form of cancer in the United States. The main cause of this cancer is DNA damage induced by the UV component of sunlight. In humans and mice, UV damage is removed by the nucleotide excision repair system. Here, we report that a rate-limiting subunit of excision repair, the xeroderma pigmentosum group A (XPA) protein, and the excision repair rate exhibit daily rhythmicity in mouse skin, with a minimum in the morning and a maximum in the afternoon/evening. In parallel with the rhythmicity of repair rate, we find that mice exposed to UV radiation (UVR) at 4:00 AM display a decreased latency and about a fivefold increased multiplicity of skin cancer (invasive squamous cell carcinoma) than mice exposed to UVR at 4:00 PM. We conclude that time of day of exposure to UVR is a contributing factor to its carcinogenicity in mice, and possibly in humans.
Canoe binds RanGTP to promote PinsTPR/Mud-mediated spindle orientation
Authors: Wee Brett , Johnston Christopher A. , Prehoda Kenneth E. , Doe Chris Q.
Published: October 2011

Regulated spindle orientation maintains epithelial tissue integrity and stem cell asymmetric cell division. In Drosophila melanogaster neural stem cells (neuroblasts), the scaffolding protein Canoe (Afadin/Af-6 in mammals) regulates spindle orientation, but its protein interaction partners and mechanism of action are unknown. In this paper, we use our recently developed induced cell polarity system to dissect the molecular mechanism of Canoe-mediated spindle orientation. We show that a previously uncharacterized portion of Canoe directly binds the Partner of Inscuteable (Pins) tetratricopeptide repeat (TPR) domain. The Canoe–PinsTPR interaction recruits Canoe to the cell cortex and is required for activation of the PinsTPR-Mud (nuclear mitotic apparatus in mammals) spindle orientation pathway. We show that the Canoe Ras-association (RA) domains directly bind RanGTP and that both the CanoeRA domains and RanGTP are required to recruit Mud to the cortex and activate the Pins/Mud/dynein spindle orientation pathway.
Single-channel Ca2+ imaging implicates Aβ1–42 amyloid pores in Alzheimer’s disease pathology
Authors: Demuro Angelo , Smith Martin , Parker Ian
Published: October 2011

Oligomeric forms of Aβ peptides are implicated in Alzheimer’s disease (AD) and disrupt membrane integrity, leading to cytosolic calcium (Ca2+) elevation. Proposed mechanisms by which Aβ mediates its effects include lipid destabilization, activation of native membrane channels, and aggregation of Aβ into Ca2+-permeable pores. We distinguished between these using total internal reflection fluorescence (TIRF) microscopy to image Ca2+ influx in Xenopus laevis oocytes. Aβ1–42 oligomers evoked single-channel Ca2+ fluorescence transients (SCCaFTs), which resembled those from classical ion channels but which were not attributable to endogenous oocyte channels. SCCaFTs displayed widely variable open probabilities (Po) and stepwise transitions among multiple amplitude levels reminiscent of subconductance levels of ion channels. The proportion of high Po, large amplitude SCCaFTs grew with time, suggesting that continued oligomer aggregation results in the formation of highly toxic pores. We conclude that formation of intrinsic Ca2+-permeable membrane pores is a major pathological mechanism in AD and introduce TIRF imaging for massively parallel single-channel studies of the incorporation, assembly, and properties of amyloidogenic oligomers.
MHC class I–specific antibody binding to nonhematopoietic cells drives complement activation to induce transfusion-related acute lung injury in mice
Authors: Strait Richard T. , Hicks Wyenona , Barasa Nathaniel , Mahler Ashley , Khodoun Marat , Köhl Jörg , Stringer Keith , Witte David , Van Rooijen Nico , Susskind Brian M. , Finkelman Fred D.
Published: October 2011

Transfusion-related acute lung injury (TRALI), a form of noncardiogenic pulmonary edema that develops during or within 6 h after a blood transfusion, is the most frequent cause of transfusion-associated death in the United States. Because development of TRALI is associated with donor antibodies (Abs) reactive with recipient major histocompatibility complex (MHC), a mouse model has been studied in which TRALI-like disease is caused by injecting mice with anti–MHC class I monoclonal Ab (mAb). Previous publications with this model have concluded that disease is caused by FcR-dependent activation of neutrophils and platelets, with production of reactive oxygen species that damage pulmonary vascular endothelium. In this study, we confirm the role of reactive oxygen species in the pathogenesis of this mouse model of TRALI and show ultrastructural evidence of pulmonary vascular injury within 5 min of anti–MHC class I mAb injection. However, we demonstrate that disease induction in this model involves macrophages rather than neutrophils or platelets, activation of complement and production of C5a rather than activation of FcγRI, FcγRIII, or FcγRIV, and binding of anti–MHC class I mAb to non-BM–derived cells such as pulmonary vascular endothelium. These observations have important implications for the prevention and treatment of TRALI.
Th17 lymphocytes traffic to the central nervous system independently of α4 integrin expression during EAE
Authors: Rothhammer Veit , Heink Sylvia , Petermann Franziska , Srivastava Rajneesh , Claussen Malte C. , Hemmer Bernhard , Korn Thomas
Published: October 2011

The integrin α4β1 (VLA-4) is used by encephalitogenic T cells to enter the central nervous system (CNS). However, both Th1 and Th17 cells are capable of inducing experimental autoimmune encephalomyelitis (EAE), and the molecular cues mediating the infiltration of Th1 versus Th17 cells into the CNS have not yet been defined. We investigated how blocking of α4 integrins affected trafficking of Th1 and Th17 cells into the CNS during EAE. Although antibody-mediated inhibition of α4 integrins prevented EAE when MOG35-55-specific Th1 cells were adoptively transferred, Th17 cells entered the brain, but not the spinal cord parenchyma, irrespective of α4 blockade. Accordingly, T cell–conditional α4-deficient mice were not resistant to actively induced EAE but showed an ataxic syndrome with predominantly supraspinal infiltrates of IL-23R+CCR6+CD4+ T cells. The entry of α4-deficient Th17 cells into the CNS was abolished by blockade of LFA-1 (αLβ2 integrin). Thus, Th1 cells preferentially infiltrate the spinal cord via an α4 integrin–mediated mechanism, whereas the entry of Th17 cells into the brain parenchyma occurs in the absence of α4 integrins but is dependent on the expression of αLβ2. These observations have implications for the understanding of lesion localization, immunosurveillance, and drug design in multiple sclerosis.
In situ induction of dendritic cell–based T cell tolerance in humanized mice and nonhuman primates
Authors: Jung Kyeong Cheon , Park Chung-Gyu , Jeon Yoon Kyung , Park Hyo Jin , Ban Young Larn , Min Hye Sook , Kim Eun Ji , Kim Ju Hyun , Kang Byung Hyun , Park Seung Pyo , Bae Youngmee , Yoon Il-Hee , Kim Yong-Hee , Lee Jae-Il , Kim Jung-Sik , Shin Jun-Seop , Yang Jaeseok , Kim Sung Joo , Rostlund Emily , Muller William A. , Park Seong Hoe
Published: October 2011

Induction of antigen-specific T cell tolerance would aid treatment of diverse immunological disorders and help prevent allograft rejection and graft versus host disease. In this study, we establish a method of inducing antigen-specific T cell tolerance in situ in diabetic humanized mice and Rhesus monkeys receiving porcine islet xenografts. Antigen-specific T cell tolerance is induced by administration of an antibody ligating a particular epitope on ICAM-1 (intercellular adhesion molecule 1). Antibody-mediated ligation of ICAM-1 on dendritic cells (DCs) led to the arrest of DCs in a semimature stage in vitro and in vivo. Ablation of DCs from mice completely abrogated anti–ICAM-1–induced antigen-specific T cell tolerance. T cell responses to unrelated antigens remained unaffected. In situ induction of DC-mediated T cell tolerance using this method may represent a potent therapeutic tool for preventing graft rejection.
Graph accordance of next-generation sequence assemblies
Authors: Yao Guohui , Ye Liang , Gao Hongyu , Minx Patrick , Warren Wesley C. , Weinstock George M.
Published: October 2011

Motivation: No individual assembly algorithm addresses all the known limitations of assembling short-length sequences. Overall reduced sequence contig length is the major problem that challenges the usage of these assemblies. We describe an algorithm to take advantages of different assembly algorithms or sequencing platforms to improve the quality of next-generation sequence (NGS) assemblies.

Results: The algorithm is implemented as a graph accordance assembly (GAA) program. The algorithm constructs an accordance graph to capture the mapping information between the target and query assemblies. Based on the accordance graph, the contigs or scaffolds of the target assembly can be extended, merged or bridged together. Extra constraints, including gap sizes, mate pairs, scaffold order and orientation, are explored to enforce those accordance operations in the correct context. We applied GAA to various chicken NGS assemblies and the results demonstrate improved contiguity statistics and higher genome and gene coverage.

Availability: GAA is implemented in OO perl and is available here: http://sourceforge.net/projects/gaa-wugi/.

Contact:  lye@genome.wustl.edu
Statistical Analysis of Endorsement Experiments: Measuring Support for Militant Groups in Pakistan
Authors: Bullock Will , Imai Kosuke , Shapiro Jacob N.
Published: October 2011

Political scientists have long been interested in citizens' support level for such actors as ethnic minorities, militant groups, and authoritarian regimes. Attempts to use direct questioning in surveys, however, have largely yielded unreliable measures of these attitudes as they are contaminated by social desirability bias and high nonresponse rates. In this paper, we develop a statistical methodology to analyze endorsement experiments, which recently have been proposed as a possible solution to this measurement problem. The commonly used statistical methods are problematic because they cannot properly combine responses across multiple policy questions, the design feature of a typical endorsement experiment. We overcome this limitation by using item response theory to estimate support levels on the same scale as the ideal points of respondents. We also show how to extend our model to incorporate a hierarchical structure of data in order to uncover spatial variation of support while recouping the loss of statistical efficiency due to indirect questioning. We illustrate the proposed methodology by applying it to measure political support for Islamist militant groups in Pakistan. Simulation studies suggest that the proposed Bayesian model yields estimates with reasonable levels of bias and statistical power. Finally, we offer several practical suggestions for improving the design and analysis of endorsement experiments.
Tirosin Kinase Inhibitors in Chronic Graft versus Host Disease: From Bench to Bedside
Authors: Olivieri Jacopo , Coluzzi Sabrina , Attolico Imma , Olivieri Attilio
Published: October 2011

Chronic Graft Versus Host Disease (cGVHD) is a major complication of allogeneic stem-cell transplantation (SCT). In many inflammatory fibrotic diseases, such as Systemic Scleroderma (SSc) and cGVHD with fibrotic features, an abnormal activation of transforming growth factor (TGFβ) and platelet-derived growth factor receptor (PDGF-R) pathways have been observed. Tyrosin Kinase Inhibitors (TKIs), which are currently used for treatment of patients with Chronic Myeloid Leukemia (CML), share potent antifibrotic and antiinflammatory properties, being powerful dual inhibitors of both PDGF-R and TGFβpathways. Moreover accumulating in vitro data confirm that TKIs, interacting with the TCR and other signalling molecules, carry potent immunomodulatory effects, being involved in both T-cell and B-cell response. Translation to the clinical setting revealed that treatment with Imatinib can achieve encouraging responses in patients with autoimmune diseases and steroid-refractory cGVHD, showing a favourable toxicity profile. While the exact mechanisms leading to such efficacy are still under investigation, use of TKIs in the context of clinical trials should be promoted, aiming to evaluate the biological changes induced in vivo by TKIs and to assess the long term outcome of these patients. Second-generation TKIs, with more favourable toxicity profile are under evaluation in the same setting.
Cellular Sequestration of Cadmium in the Hyperaccumulator Plant Species Sedum alfredii
Authors: Tian Shengke , Lu Lingli , Labavitch John , Yang Xiaoe , He Zhenli , Hu Hening , Sarangi Ritimukta , Newville Matt , Commisso Joel , Brown Patrick
Published: October 2011

Spatial imaging of cadmium (Cd) in the hyperaccumulator Sedum alfredii was investigated in vivo by laser ablation inductively coupled plasma mass spectrometry and x-ray microfluorescence imaging. Preferential Cd accumulation in the pith and cortex was observed in stems of the Cd hyperaccumulating ecotype (HE), whereas Cd was restricted to the vascular bundles in its contrasting nonhyperaccumulating ecotype. Cd concentrations of up to 15,000 μg g−1 were measured in the pith cells, which was many fold higher than the concentrations in the stem epidermis and vascular bundles in the HE plants. In the leaves of the HE, Cd was mainly localized to the mesophyll and vascular cells rather than the epidermis. The distribution pattern of Cd in both stems and leaves of the HE was very similar to calcium but not zinc, irrespective of Cd exposure levels. Extended x-ray absorption fine structure spectroscopy analysis showed that Cd in the stems and leaves of the HE was mainly associated with oxygen ligands, and a larger proportion (about 70% in leaves and 47% in stems) of Cd was bound with malic acid, which was the major organic acid in the shoots of the plants. These results indicate that a majority of Cd in HE accumulates in the parenchyma cells, especially in stems, and is likely associated with calcium pathways and bound with organic acid (malate), which is indicative of a critical role of vacuolar sequestration of Cd in the HE S. alfredii.
Schooling behaviour of juvenile Pacific bluefin tuna Thunnus orientalis depends on their vision development
Authors: Torisawa S. , Fukuda H. , Suzuki K. , Takagi T.
Published: October 2011

The effects of vision development and light intensity on schooling behaviour during growth in juvenile Pacific bluefin tuna Thunnus orientalis were investigated using both behavioural and histological approaches. The schooling behaviour of three age groups [25, 40 and 55 days post hatching (dph)] of juvenile T. orinetalis were examined under various light intensities. Subsequently, schooling variables, such as the nearest neighbour distance (DNN) and the separation swimming index (ISS), were also measured under different light intensities. Furthermore, retinal indices of light adaptation in juvenile fish at each experimental light intensity and visual acuities in six stages (25–55 dph) of juveniles were examined histologically. During growth, the light intensity thresholds of ISS decreased from 5 to 0·05 lx, and DNN under light conditions (>300 lx) also decreased from 9·2 times the standard length (LS) to 1·2 times LS. The thresholds of light intensities for the light adaptation of retinas in juveniles (25–55 dph) similarly decreased from 5 to 0·05 lx with growth. In addition, the visual acuities of juveniles developed from 0·04 to 0·17 with decreasing DNN. These data clearly indicate that the characteristics of schooling behaviour strongly correspond to the degree of vision development. Juvenile T. orinetalis also appear to be more dependent on cone rather than rod cells under low light intensity conditions, resulting in a relatively high light intensity threshold for schooling. These results suggest that juveniles can adapt to darker conditions during growth by developing improved visual capabilities.
Association of the (CA)n repeat polymorphism of insulin‐like growth factor‐I and −202 A/C IGF‐binding protein‐3 promoter polymorphism with adult height in patients with severe growth hormone deficiency
Authors: Miletta Maria Consolata , Scheidegger Ursina A. , Giordano Mara , Bozzola Mauro , Pagani Sara , Bona Gianni , Dattani Mehul , Hindmarsh Peter C. , Petkovic Vibor , Oser‐Meier Monika , Flück Christa E. , Mullis Primus‐E.
Published: October 2011

Objective  A number of mathematical models for predicting growth and final height outcome have been proposed to enable the clinician to ‘individualize’ growth‐promoting treatment. However, despite optimizing these models, many patients with isolated growth hormone deficiency (IGHD) do not reach their target height. The aim of this study was to analyse the impact of polymorphic genotypes [CA repeat promoter polymorphism of insulin‐like growth factor‐I (IGF‐I) and the −202 A/C promoter polymorphism of IGF‐Binding Protein‐3 (IGFBP‐3)] on variable growth factors as well as final height in severe IGHD following GH treatment.

Design, Patients and Controls  One hundred seventy eight (IGF‐I) and 167 (IGFBP‐3) subjects with severe growth retardation because of IGHD were studied. In addition, the various genotypes were also studied in a healthy control group of 211 subjects.

Results  The frequency of the individual IGF‐I (CA)n repeats ranging from 10 to 24, with the most frequent allele containing CA19, was similar in controls and in IGHD subjects. However, in controls, the pooled CA19 and CA20 as well as −202 A IGFBP‐3 alleles were significantly (P < 0·01 and P < 0·001) more common in the taller [≥2 to 0 standard deviation score (SDS)] when compared with the shorter subgroup (<0 to ≤−2 SDS). Overall, the effect of recombinant human growth hormone (rhGH) replacement did not reveal any difference between the various genotypes in terms of final height. Independent of their genotype, all subjects showed a slightly lower adult height SDS compared with midparental height SDS.

Conclusion  Our results indicate that in patients with severe IGHD, although the various IGF‐I and IGFBP‐3 genotypes may play a role in GH responsiveness, there was no effect on final height.
Safety of zoster vaccine in adults from a large managed‐care cohort: a Vaccine Safety Datalink study
Authors: Tseng H. F. , Liu A. , Sy L. , Marcy S. M. , Fireman B. , Weintraub E. , Baggs J. , Weinmann S. , Baxter R. , Nordin J. , Daley M. F. , Jackson L. , Jacobsen S. J. ,   for the Vaccine Safety Datalink (VSD) Team
Published: October 2011

Abstract.  Tseng HF, Liu A, Sy L, Marcy SM, Fireman B, Weintraub E, Baggs J, Weinmann S, Baxter R, Nordin J, Daley MF, Jackson L, Jacobsen SJ, for the Vaccine Safety Datalink (VSD) Team (Kaiser Permanente, Pasadena, CA; Kaiser Permanente, Oakland, CA; Centers for Disease Control and Prevention, Atlanta, GA; Kaiser Permanente, Portland, OR; HealthPartners Research Foundation, Minneapolis, MN; Kaiser Permanente, Denver, CO; and Group Health Cooperative of Puget Sound, Seattle, WA; USA). Safety of zoster vaccine in adults from a large managed‐care cohort: a Vaccine Safety Datalink study. J Intern Med 2012; 271: 510–520.

Objectives.  The aim of this study was to examine a large cohort of adults who received the zoster vaccine for evidence of an increased risk of prespecified adverse events requiring medical attention.

Design.  Two self‐comparison approaches, including a case‐centred approach and a self‐controlled case series (SCCS) analysis were used.

Setting.  Eight managed‐care organizations participating in the Vaccine Safety Datalink project in the United States.

Subjects.  A total of 193 083 adults aged 50 and older receiving a zoster vaccine from 1 January 2007 to 31 December 2008 were included.

Main outcome measures.  Prespecified adverse events were identified by aggregated International Classification of Diseases, Ninth Revision (ICD‐9) codes in automated health plan datasets.

Results.  The risk of allergic reaction was significantly increased within 1–7 days of vaccination [relative risk = 2.13, 95% confidence interval (CI): 1.87–2.40 by case‐centred method and relative rate = 2.32, 95% CI: 1.85–2.91 by SCCS]. No increased risk was found for the following adverse event groupings: cerebrovascular events; cardiovascular events; meningitis; encephalitis; and encephalopathy; and Ramsay‐Hunt syndrome and Bell’s palsy.

Conclusions.  The results of this study support the findings from the prelicensure clinical trials, providing reassurance that the zoster vaccine is generally safe and well‐tolerated with a small increased risk of allergic reactions in 1–7 days after vaccination.
Risk of ischaemic heart disease and cardiomyopathy in patients with haemochromatosis and in their first‐degree relatives: a nationwide, population‐based study
Authors: Elmberg M. , Hultcrantz R. , Simard J. F. , Stål P. , Pehrsson K. , Askling J.
Published: October 2011

Abstract.  Elmberg M, Hultcrantz R, Simard JF, Stål P, Pehrsson K, Askling J (Karolinska University Hospital and Karolinska Institutet, Solna; Karolinska Institutet, Huddinge; Karolinska Institutet, Solna; Karolinska Institutet, Huddinge, Karolinska University Hospital; Karolinska Institutet, Solna; Sweden). Risk of ischaemic heart disease and cardiomyopathy in patients with haemochromatosis and in their first‐degree relatives: a nationwide, population‐based study. J Intern Med 2012; 272: 45–54.

Background  Iron‐loaded macrophages increase atherosclerosis formation. Genetic haemochromatosis (GH) is an autosomal recessive disease characterized by iron overload, for example in the myocardium, but the reticuloendothelial system is depleted of iron. In contrast to the elevated risk of cardiomyopathy in GH, the risk of ischaemic heart disease (IHD) may therefore not be increased. Little is known of these risks among heterozygotes also being first‐degree relatives (FDRs), thus sharing other factors for phenotypic expression of GH.

Objective  To assess the risks of IHD and cardiomyopathy among haemochromatosis patients and their FDRs.

Design  Population‐based cohort study.

Setting and subjects  A total of 3531 haemochromatosis patients and 11 794 FDRs were identified using nationwide, population‐based health and census registers. Matched (1:10) population controls were randomly selected. Individuals with a record of IHD and cardiomyopathy during 1997–2005 were identified through linkage with the National Patient Register. Relative risks were estimated using Cox proportional hazard regression.

Results  Of the 3531 patients, 259 were diagnosed with IHD compared with 3077 of the 37 369 controls [hazard ratio (HR) = 1.17; 95% CI, 1.03–1.33]. Based on 30 patients versus 115 controls, the HR for cardiomyopathy was 3.21 (95% CI, 2.15–4.81). Of 11 794 FDRs of haemochromatosis patients, 582 were registered with IHD compared with 6197 among FDRs of controls (HR = 1.05; 95% CI, 0.97–1.15). Based on 28 FDRs of patients versus 291 FDRs of controls registered with cardiomyopathy, the HR for cardiomyopathy was 1.06 (95% CI, 0.72–1.56).

Conclusions  In patients with haemochromatosis, the increased risk of cardiomyopathy is much more pronounced than that of IHD, which is barely elevated. FDRs of haemochromatosis patients are not at increased risk of cardiomyopathy or IHD.
Therapeutic Effects of Combination Using Glucosamine Plus Tacrolimus (FK‐506) on The Development of Atopic Dermatitis‐Like Skin Lesions in NC/Nga Mice
Authors: Kim C.‐H. , Cheong K. A. , Park C. D. , Lee A.‐Y.
Published: October 2011

Tacrolimus (FK‐506) has been found to exhibit potent inhibitory effects on spontaneously developed dermatitis. We previously showed that glucosamine prevents the development of Atopic dermatitis (AD)‐like skin lesions in NC/Nga mice. The aims of our study were to investigate the synergistic therapeutic efficacy of combination of glucosamine plus FK‐506 in dermatophagoides farina (Df)‐induced AD‐like skin lesions in NC/Nga mice and to determine the underlying therapeutic mechanisms. The Df‐induced NC/Nga mice with a clinical score of 8 were used for treatment with glucosamine (500 mg/kg) alone, FK‐506 (1.0 mg/kg) or in combination. The synergistic effects of combination therapy were evaluated by dermatitis scores, skin histology and immunological parameters such as IgE, Th2‐mediated cytokines and chemokines, CD3+ T cells and CLA+ T cells. Combined therapy using glucosamine plus FK‐506 improved the development of AD‐like skin lesions as exemplified by a significant decrease in total skin symptom severity scores. The suppression of dermatitis by combined therapy was accompanied by a decrease in the plasma level of IgE and in the splenic level of IL‐5, IL‐13, TARC and eotaxin. Histological finding indicated that the dermal infiltration of inflammatory cells including mast cells and eosinophils was greatly reduced. Particularly, immunohistological evaluation reveals a reduction in CD3+ T cells and CLA+ cells in the combined therapy. Our findings suggest that combination therapy of glucosamine plus FK‐506 was more synergistic efficacy than single‐modality treatment with either alone to improve the development of established dermatitis in NC/Nga mice model. This combined immunosuppressive therapy may provide an effective therapeutic strategy for the treatment of AD.
Elongator complex is critical for cell cycle progression and leaf patterning in Arabidopsis
Authors: Xu Deyang , Huang Weihua , Li Yang , Wang Hua , Huang Hai , Cui Xiaofeng
Published: October 2011

The mitotic cell cycle in higher eukaryotes is of pivotal importance for organ growth and development. Here, we report that Elongator, an evolutionarily conserved histone acetyltransferase complex, acts as an important regulator of mitotic cell cycle to promote leaf patterning in Arabidopsis. Mutations in genes encoding Elongator subunits resulted in aberrant cell cycle progression, and the altered cell division affects leaf polarity formation. The defective cell cycle progression is caused by aberrant DNA replication and increased DNA damage, which activate the DNA replication checkpoint to arrest the cell cycle. Elongator interacts with proliferating cell nuclear antigen (PCNA) and is required for efficient histone 3 (H3) and H4 acetylation coupled with DNA replication. Levels of chromatin‐bound H3K56Ac and H4K5Ac known to associate with replicons during DNA replication were reduced in the mutants of both Elongator and chromatin assembly factor 1 (CAF‐1), another protein complex that physically interacts with PCNA for DNA replication‐coupled chromatin assembly. Disruptions of CAF‐1 also led to severe leaf polarity defects, which indicated that Elongator and CAF‐1 act, at least partially, in the same pathway to promote cell cycle progression. Collectively, our results demonstrate that Elongator is an important regulator of mitotic cell cycle, and the Elongator pathway plays critical roles in promoting leaf polarity formation.
Reproductive Performance is Improved During Seasonal Anoestrus when Female and Male Murciano–Granadina Goats Receive Melatonin Implants and in Payoya Goats when Females are thus Treated
Authors: Zarazaga LA , Gatica MC , Celi I , Guzmán JL
Published: October 2011

Contents

This work investigates whether the reproductive performance of Mediterranean goats achieved using melatonin implants at around the spring equinox is affected by the protocol followed, i.e. implanting females only, males only, both sexes or neither sex. In a first experiment, Murciano–Granadina females (n = 419, 510 and 631 for three consecutive years) were divided into four groups: treated with melatonin (FM) and not treated with melatonin (FC), mounted by males treated with melatonin (MM) or not (MC). In a second experiment, performed during 2009, the same protocols were used with 635 Payoya females and the results compared with those obtained for the same year for the Murciano–Granadina breed. Fertility (percentage of goats kidding), litter size (number of kids born per female kidded) and productivity (number of kids per female in each mating group) were calculated. In the first experiment, better reproductive performances were obtained when females (overall fertility: 71.1% vs 57.0% for the FM and FC animals; productivity 1.37 ± 0.04 kids per female vs 1.12 ± 0.03 kids per female for the FM and FC animals; p < 0.01) or males (overall fertility: 65.9% vs 58.4 for the MM and MC animals; productivity 1.28 ± 0.03 kids per female vs 1.13 ± 0.04 kids per female for MM and MC groups, respectively; p < 0.01) were implanted with melatonin. Moreover, the interaction sex × melatonin treatment had a significant effect (p < 0.05) on productivity. In the second experiment, for the Murciano–Granadina breed, the greatest increase in the number of kids born per female was obtained when the females were treated with melatonin, in either the FM/MC or FM/MM protocols (0.54 extra kids and 0.53 extra kids per female, respectively) (p < 0.01). In the Payoya breed, the greatest increase was obtained using the FM/MC protocol (0.19 extra kids per female). Thus, improved reproductive performances are obtained when female Murciano–Granadina and Payoya goats are implanted with melatonin, although important differences in reproductive performance are seen between the breeds.
Effect of gelatinase inhibition on adipogenesis and adipose tissue development
Authors: Van Hul M , Bauters D , Himmelreich U , Kindt N , Noppen B , Vanhove M , Lijnen HR
Published: October 2011

1. The potential of the matrix metalloproteinase (MMP) inhibitor ABT‐518 to affect pre‐adipocyte differentiation in vitro and adipose tissue development in vivo was investigated using mouse models of adipogenesis and obesity.

2. Differentiation of 3T3‐F442A pre‐adipocytes into mature adipocytes was enhanced in a dose‐dependent manner by the addition of ABT‐518 (0–100 μmol/L). This was associated with increased expression of the adipogenic markers adipocyte fatty acid‐binding protein 2 (AP2), peroxisome proliferator‐activated receptor γ and adiponectin.

3. Feeding 5‐week‐old male wild‐type mice with a high‐fat diet, with or without ABT‐518 (to achieve a dose of 100 mg/kg per day), for 16 weeks resulted in a significant reduction in bodyweight throughout the experimental period. Magnetic resonance spectroscopy revealed that the lipid : water ratio was significantly lower in ABT‐518‐treated mice. The total weight of isolated subcutaneous or gonadal fat depots did not differ significantly following ABT‐518 treatment, but adipocyte and blood vessel size were significantly reduced in the gonadal fat.

4. Administration of ABT‐518–2 (100 mg/kg per day for 10 weeks) to 5‐week‐old male wild‐type mice with established obesity maintained on a high‐fat diet had no effect on total bodyweight at the end of the experiment, but was associated with reduced blood vessel size in the fat depots.

5. Thus, the MMP inhibitor ABT‐518 stimulates differentiation of 3T3‐F442A pre‐adipocytes in vitro. It mildly reduces bodyweight gain in a murine model of diet‐induced obesity, but does not affect established obesity.
Efficacy and safety of cinacalcet for the treatment of secondary hyperparathyroidism in patients with advanced chronic kidney disease before initiation of regular dialysis
Authors: MONTENEGRO JESÚS , CORNAGO IÑAKI , GALLARDO ISABEL , GARCÍA‐LEDESMA PAULA , HERNANDO AINHOA , MARTINEZ ISABEL , MUÑOZ ROSA I , ROMERO MARCO A
Published: October 2011

Aim:  To evaluate the compassionate use of cinacalcet for the management of secondary hyperparathyroidism in patients who are not on dialysis.

Methods:  Patients with stage 4–5 chronic kidney disease (CKD) who were not on dialysis, had an intact parathyroid hormone (iPTH) level greater than 300 pg/mL, and had not responded satisfactorily to treatment with phosphate binders and vitamin D were prospectively studied. Patients received 6 months of compassionate treatment with cinacalcet, which was initiated at a dose of 30 mg/day orally and flexibly dosed thereafter based on iPTH levels.

Results:  Twenty‐six patients with a mean age ± standard deviation (SD) of 58.8 ± 16.1 years were enrolled in the study and included in the statistical analysis. The mean percentage change in iPTH levels from baseline after 6 months of treatment was −67.9 ± 17.0%, with 92.3% (95% confidence interval (CI), 75.9–97.9) of patients showing an iPTH level within the limits recommended by Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. The mean serum calcium concentrations had decreased significantly at the end of the study (−8.0 ± 6.9%), while the mean serum phosphorus concentration had significantly increased (+8.3 ± 17.0%).

Conclusion:  Our results suggest that cinacalcet may be a useful alternative for the treatment of secondary hyperparathyroidism in pre‐dialysis patients who are unresponsive to other treatments. The hypocalcemia and hyperphosphatemia reported in previous studies may not occur if a moderate dose of calcimimetics is used in patients with marginal glomerular filtration rates, especially if combined with vitamin D analogues and calcium‐based phosphate binders.
Dorsal penile nerve block for male pediatric circumcision – randomized comparison of ultrasound‐guided vs anatomical landmark technique
Authors: O’Sullivan Michael J. , Mislovic Branislav , Alexander Elise
Published: October 2011

Background:  Dorsal penile nerve block (DPNB) is a commonly performed regional anesthetic technique for male circumcision. Traditionally, DPNB is based on an anatomical landmark technique. Recently, an ultrasound‐guided technique for DPNB has been described.

Objectives:  The aim of our study was to compare the anatomical landmark technique with this ultrasound‐guided technique. The hypothesis to be tested was that ultrasound guidance of DPNB would lead to less administration of opioid when compared to the anatomical landmark technique.

Methods:  Boys of ASA status I/II scheduled for day case circumcision were prospectively recruited and randomized. DPNB was performed under general anesthesia using the anatomical landmark technique or ultrasound guidance. Fentanyl was administered intraoperatively and immediately postoperatively if patients demonstrated signs of pain. Similarly, oral codeine was given prior to discharge if required. The primary outcome measure was the number of patients requiring fentanyl. Secondary outcome measures included initial pain score on emergence from general anesthesia, requirement for codeine predischarge, and time to perform block.

Results:  A total of 32 patients were recruited to the landmark group and 34 to the ultrasound group. There was no significant difference between the two groups in terms of fentanyl administration. The ultrasound technique took longer to perform but was associated with a reduction in codeine requirement prior to discharge.

Conclusions:  This study does not support the routine use of ultrasound for the performance of DPNB in male pediatric circumcision. Nonetheless, an associated reduction in codeine administration postoperatively suggests some benefit in terms of postoperative pain.
Dynamic Parameter Identification of Secondary Mass Dampers Based on Full‐Scale Tests
Authors: Cho Bong‐Ho , Jo Ji‐Seong , Joo Seok‐Jun , Kim Hongjin
Published: October 2011

Abstract:  For a secondary mass damper such as tuned liquid damper (TLD) or tuned liquid column damper (TLCD), whose moving mass is liquid, it is impossible to prefabricate the damper in a factory for the identification of dynamic properties. Also, it is not easy to prefabricate a concrete tuned mass damper (TMD), whose moving mass is made of concrete, in a factory. In this article, an identification method for finding dynamic properties of secondary mass dampers based on the full‐scale field test is presented. Decoupled equations of motion are derived from a coupled equation of motion of building and damper. The decoupled equations of motion are then used for system identification using the response of the damper as an input and the response of the building as an output. The proposed method is applied to numerical examples and an actual TMD and TLCD installed in buildings.
An empirical analysis of the determinants of technology roadmap utilization
Authors: Lee Jung Hoon , Phaal Robert , Lee Chihoon
Published: October 2011

For many years now, firms have managed their research and development (R&D) by applying various approaches drawn from the discipline of technology roadmapping (TRM). The underlying rationale of these roadmapping approaches is to align firms' product and technology developments with their business goals. By visually representing firms' technology strategy, roadmaps support intra‐firm communication and facilitate the coordination of strategic decisions and activities within the technology management domain. Most previously published research on TRMs has focused on the design and implementation of roadmapping processes; that is, relatively few empirical or quantitative studies describe the use and evaluation of roadmapping techniques. This paper seeks to address this gap by conducting a survey of 186 different R&D units within stock market‐listed companies in Korea that have implemented TRM. The paper attempts to identify the antecedent factors behind firms' successful use of roadmaps, further identifying correlations between these antecedent factors through an analysis of the R&D units. It also empirically highlights these antecedent factors by empirically analyzing and verifying correlations between roadmap utilization and R&D performance.
Is there evidence for the use of art therapy in treatment of psychosomatic disorders, eating disorders and crisis? A comparative study of two different systems for evaluation
Authors: HOLMQVIST GÄRD , PERSSON CRISTINA LUNDQVIST
Published: October 2011

Holmqvist, G. & Lundqvist Persson, C. (2012). Is there evidence for the use of art therapy in treatment of psychosomatic disorders, eating disorders and crisis? A comparative study of two different systems for evaluation. Scandinavian Journal of Psychology 53, 47–53.

As with any type of treatment the requirement for evidence based practice (EBP) has also affected art therapy (AT) when used as an intervention. This review evaluates the available evidence for using AT for psychosomatic disorders, eating disorders and crisis. The search in Cochrane, Best Practice, AMED, CINAHL, PION, PsycINFO and PubMed from 1987 until now resulted in a huge number of articles but only 32 articles met our criteria for evaluations. The articles were assessed with two evaluation systems, the GRADE system used by the Swedish Council on Health Technology Assessment (SBU) and the US Preventive Services Task Force (USPSTF/Task Force). When comparing the results we found that the GRADE evaluation system rejected the quality in 84% of the 32 studies and the USPSTF/Task Force 41% of these studies. An evidence base for AT was found only according to the criteria of USPSTF/Task Force. Hence, the evidence concept is not explicit, which means that effective treatments run a risk of not being implemented in health care. We suggest a broader view of what constitutes evidence in order to make it possible to include different types of research designs and methods.
Executive function deficits in preschool children with ADHD and DBD
Authors: Schoemaker Kim , Bunte Tessa , Wiebe Sandra A. , Espy Kimberly Andrews , Deković Maja , Matthys Walter
Published: October 2011

Background:  Impairments in executive functions (EF) are consistently associated with attention deficit hyperactivity disorder (ADHD) and to a lesser extent, with disruptive behavior disorder (DBD), that is, oppositional defiant disorder or conduct disorder, in school‐aged children. Recently, larger numbers of children with these disorders are diagnosed earlier in development, yet knowledge about impairments in clinically diagnosed preschool children and the role of comorbidity is limited. Therefore, the aim of the current study was to examine EF in clinically referred preschool children with a clinical diagnosis of ADHD, DBD and ADHD + DBD.

Method:  Participants were 202 children aged 3.5–5.5 years, 61 with ADHD only, 33 with DBD only, 52 with comorbid ADHD + DBD and 56 typically developing children. Five EF tasks were administered.

Results:  Confirmatory factor analysis showed that the two‐factor model (inhibition and working memory) fit the data better than a one‐factor model in this clinical sample. Preschoolers with ADHD displayed inhibition deficits, also after controlling for IQ. Likewise, preschoolers with DBD displayed impaired inhibition, but when IQ was controlled differences were carried mostly by the effect on the task where motivational demands were high (i.e. when tangible rewards were used). This pattern was also found in the interaction between ADHD and DBD; impaired inhibition in the comorbid group, however, was more severe than in the DBD group. Regarding working memory, few group differences were found.

Conclusions:  Clinically diagnosed preschool children with ADHD showed robust inhibition deficits, whereas preschool children with DBD showed impaired inhibition especially where motivational incentives were prominent. Severity of inhibition impairment in the comorbid group was similar to the ADHD group.
Longitudinal study of neurological soft signs in first‐episode early‐onset psychosis
Authors: Mayoral M. , Bombín I. , Castro‐Fornieles J. , González‐Pinto A. , Otero S. , Parellada M. , Moreno D. , Baeza I. , Graell M. , Rapado M. , Arango C.
Published: October 2011

Background:  In recent decades, the assessment of neurological soft signs (NSS) in patients with psychosis has become a subject of special interest. The study of the progression of NSS during adolescence will provide valuable information about the role of NSS as endophenotypes or biomarkers and about brain development at a stage in which brain maturation has not yet been completed.

Methods:  Neurological soft signs were assessed in a sample of 110 first episodes of early‐onset psychosis (EOP) and 98 healthy children and adolescents at two different times in a 2‐year follow‐up period.

Results:  Patients with EOP showed more NSS than controls both at baseline (p < .001) and the 2‐year follow‐up (p < .001). No differences were found in the number of signs among the different diagnostic subgroups (schizophrenia, bipolar disorder, and other psychoses). When we examined the changes in NSS over the follow‐up, the reduction of NSS in the patients was greater than the controls for ‘Motor coordination’ (p = .032), ‘Others’ (p < .001), and ‘Total score’ (p < .001) of the NES.

Conclusion:  Despite the greater reduction of NSS in patients than in controls along the follow‐up, patients still have more neurological signs than healthy controls; therefore, these signs may be considered a trait marker. NSS do not seem to be specific to schizophrenia as they are present in different EOPs.
Seroprevalence of xenotropic murine leukemia virus–related virus in normal and retrovirus‐infected blood donors
Authors: Qiu Xiaoxing , Swanson Priscilla , Tang Ning , Leckie Gregor W. , Devare Sushil G. , Schochetman Gerald , Hackett Jr John
Published: October 2011

BACKGROUND: Xenotropic murine leukemia virus–related virus (XMRV) has been reported in patients with prostate cancer and chronic fatigue syndrome. Although results have been conflicting, the potential of XMRV as an infectious human retrovirus has raised concerns about transfusion safety. To address this issue, normal and retrovirus‐infected blood donors were screened for evidence of XMRV infection.

STUDY DESIGN AND METHODS: Plasma from 1000 US, 100 human immunodeficiency virus Type 1–infected Cameroonian, and 642 human T‐lymphotropic virus Type I (HTLV‐I)‐infected or uninfected Japanese blood donors as well as 311 sexually transmitted disease diagnostic specimens were screened for antibodies to XMRV gp70 and p15E using chemiluminescent immunoassays (CMIAs). CMIA‐reactive samples were evaluated by p30 CMIA, Western blot, and real‐time reverse transcriptase polymerase chain reaction.

RESULTS: XMRV seroreactivity was low (0%‐0.6%) with the exception of the HTLV‐I–infected donors (4.9%). Antibody was detected against only a single XMRV protein (p15E or gp70); none of the seroreactive samples had detectable XMRV pol or env sequences. The elevated seroreactivity in HTLV‐I–infected donors was due to an increased p15E seroreactive rate (4.1%). Inspection of XMRV and HTLV sequences revealed a high level of conservation within the immunodominant region (IDR) of the transmembrane protein. In some cases, HTLV IDR peptide competitively reduced the XMRV p15E signal.

CONCLUSIONS: Based on the low prevalence of seroreactivity, detection of antibody to only a single XMRV protein and the absence of XMRV sequences, this study finds no compelling evidence of XMRV in normal or retrovirus‐infected blood donors. The increased p15E seroreactivity observed in HTLV infection is likely due to cross‐reactive antibodies.