bluuebunny/crossref_metadata_2025 huggingface dataset:
Motivation of human resources for health: a case study at rural district level in Tanzania
Authors: Zinnen Véronique , Paul Elisabeth , Mwisongo Aziza , Nyato Daniel , Robert Annie
Published: June 2012

An increasing number of studies explore the association between financial and non‐financial incentives and the retention of health workers in developing countries. This study aims to contribute to empirical evidence on human resource for health motivation factors to assist policy makers in promoting effective and realistic interventions. A cross‐sectional survey was conducted in four rural Tanzanian districts to explore staff stability and health workers' motivation. Data were collected using qualitative and quantitative techniques, covering all levels and types of health facilities. Stability of staff was found to be quite high. Public institutions remained very attractive with better job security, salary and retirement benefits. Satisfaction over working conditions was very low owing to inadequate working equipment, work overload, lack of services, difficult environment, favouritism and ‘empty promotions’. Positive incentives mentioned were support for career development and supportive supervision. Attracting new staff in rural areas appeared to be more difficult than retaining staff in place. The study concluded that strategies to better motivate health personnel should focus on adequate remuneration, positive working and living environment and supportive management. However, by multiplying health facilities, the latest Tanzanian human resource for health plan could jeopardize current positive results. Copyright © 2012 John Wiley & Sons, Ltd.
Soil moisture and rainfall intensity thresholds for runoff generation in southwestern Wisconsin agricultural watersheds
Authors: Radatz Timothy F. , Thompson Anita M. , Madison Frederick W.
Published: June 2012

The goal of this study was to improve understanding of the factors that influence runoff generation during non‐frozen ground periods in small agricultural watersheds in southwestern Wisconsin where the landscapes are controlled by dolostone bedrock in order to provide agricultural producers with a manure management tool. Six small watersheds (ranging from 6 to 17 ha) within two southwestern Wisconsin farm sites (Discovery Farms Program (DFP) and Pioneer Farm (PF)) were instrumented, and surface runoff was continuously monitored from 2004 to 2007. The soils in all watersheds were formed in deep (~1 m) loessial sites. A direct‐plant management strategy and corn‐soybean crop rotation were utilized within watersheds at DFP. A conventional tillage system (chisel plow in the fall followed by soil finisher in the spring) and a corn‐oat‐alfalfa crop rotation were utilized within watersheds at PF. At PF, the amount of precipitation leaving the landscape as surface runoff (1.8%) was two times greater compared to DFP (0.9%), indicating that the direct‐plant management system was better at retaining precipitation than the chisel plow/soil finisher system. Using breakpoint regression analysis, a non‐linear response in runoff generation with antecedent soil moisture (ASM) was observed with a threshold ASM of 0.39 cm3cm−3(approximately 80% of total porosity) for all six watersheds. Below this threshold, runoff coefficients were near zero. Above this threshold, runoff coefficients increased with ASM. A non‐linear response in runoff generation with maximum 30 min rainfall intensity (I30) was also observed, and threshold I30 values increased as ASM decreased and as crop cover increased. Copyright © 2012 John Wiley & Sons, Ltd.
NOS‐2 signaling and cancer therapy
Authors: Bian Ka , Ghassemi Farshid , Sotolongo Alex , Siu Alan , Shauger Lauren , Kots Alex , Murad Ferid
Published: June 2012

The role of NO and cGMP signaling in tumor biology has been extensively studied during the past three decades. However, whether the pathway is beneficial or detrimental in cancer is still open to question. We suggest several reasons for this ambiguity: first, although NO participates in normal signaling (e.g., vasodilation and neurotransmission), NO is also a cytotoxic or apoptotic molecule when produced at high concentrations by inducible nitric‐oxide synthase (iNOS or NOS‐2). In addition, the cGMP‐dependent (NO/sGC/cGMP pathway) and cGMP‐independent (NO oxidative pathway) components may vary among different tissues and cell types. Furthermore, solid tumors contain two compartments: the parenchyma (neoplastic cells) and the stroma (nonmalignant supporting tissues including connective tissue, blood vessels, and inflammatory cells) with different NO biology. Thus, the NO/sGC/cGMP signaling molecules in tumors as well as the surrounding tissue must be further characterized before targeting this signaling pathway for tumor therapy. In this review, we focus on the NOS‐2 expression in tumor and surrounding cells and summarized research outcome in terms of cancer therapy. We propose that a normal function of the sGC‐cGMP signaling axis may be important for the prevention and/or treatment of malignant tumors. Inhibiting NOS‐2 overexpression and the tumor inflammatory microenvironment, combined with normalization of the sGC/cGMP signaling may be a favorable alternative to chemotherapy and radiotherapy for malignant tumors. © 2012 IUBMB IUBMB Life, 64(8): 676–683, 2012
TRAF3 negatively regulates calcineurin‐NFAT pathway by targeting calcineurin B subunit for degradation
Authors: Wang Xinyu , Huang Yi , Li Li , Wei Qun
Published: June 2012

Calcineurin (CN) is the only serine/threonine specific protein phosphatase regulated by Ca2+/calmodulin (CaM), which is composed of catalytic A subunit (CNA) and regulatory B subunit (CNB). Tumor necrosis factor (TNF) receptor associated factor 3 (TRAF3) is an essential component in the Toll like receptors and TNF receptors (TNFRs) pathways. The TRAF domain of TRAF3 interacts with a large range of proteins, which share consensus sequences known as TRAF interacting motifs (TIMs). By sequence alignment, we identified two potential TIMs in CNB. However, the relation between TRAF3 and CN has not been reported before. To explore this, we highly expressed the former insoluble TRAF domain of TRAF3 in soluble form by using CaM fusion system for the first time. We demonstrated that the TRAF domain of TRAF3 interacted with CNB. On further investigation, over‐expression of TRAF3 inhibited endogenous CN's activity, which decreased NFAT reporter activity and IL‐2 production. Knock‐down of TRAF3 partially enhanced CN's activity. The possible mechanism was that TRAF3 functioned as ubiquitin E3 ligase for CN and promoted its degradation. © 2012 IUBMB IUBMB Life IUBMB Life, 64(9): 748–756, 2012
HOW EFFECTIVE ARE UNEMPLOYMENT BENEFIT SANCTIONS? LOOKING BEYOND UNEMPLOYMENT EXIT
Authors: Arni Patrick , Lalive Rafael , Van Ours Jan C.
Published: June 2012

This paper provides a comprehensive evaluation of the effects of benefit sanctions on post‐unemployment outcomes such as post‐unemployment employment stability and earnings. We use rich register data which allow us to distinguish between a warning that a benefit reduction may take place in the near future and the actual withdrawal of unemployment benefits. Adopting a multivariate mixed proportional hazard approach to address selectivity, we find that warnings do not affect subsequent employment stability but do reduce post‐unemployment earnings. Actual benefit reductions lower the quality of post‐unemployment jobs both in terms of job duration as well as in terms of earnings. Copyright © 2012 John Wiley & Sons, Ltd.
Expedited analysis of DFT outputs: Introducing moanalyzer
Authors: Delgado‐Jaime Mario Ulises , DeBeer Serena
Published: June 2012

MOAnalyzer, a Matlab‐based program, has been developed to facilitate the analysis of density functional theory output files from ORCA. The program allows the user to define fragments within a molecule and then provides information on the contribution of each fragment to the molecular orbitals based on the Loewdin population analysis. Correlations to spectroscopy (X‐ray absorption and X‐ray emission) are also obtained, and the resulting information can be visualized in tables or MO diagrams. © 2012 Wiley Periodicals, Inc.
MOVIPAC: Vibrational spectroscopy with a robust meta‐program for massively parallel standard and inverse calculations
Authors: Weymuth Thomas , Haag Moritz P. , Kiewisch Karin , Luber Sandra , Schenk Stephan , Jacob Christoph R. , Herrmann Carmen , Neugebauer Johannes , Reiher Markus
Published: June 2012

We present the software package MOVIPAC for calculations of vibrational spectra, namely infrared, Raman, and Raman Optical Activity (ROA) spectra, in a massively parallelized fashion. MOVIPAC unites the latest versions of the programs SNF and AKIRA alongside with a range of helpful add‐ons to analyze and interpret the data obtained in the calculations. With its efficient parallelization and meta‐program design, MOVIPAC focuses in particular on the calculation of vibrational spectra of very large molecules containing on the order of a hundred atoms. For this purpose, it also offers different subsystem approaches such as Mode‐ and Intensity‐Tracking to selectively calculate specific features of the full spectrum. Furthermore, an approximation to the entire spectrum can be obtained using the Cartesian Tensor Transfer Method. We illustrate these capabilities using the example of a large π‐helix consisting of 20 (S)‐alanine residues. In particular, we investigate the ROA spectrum of this structure and compare it to the spectra of α‐ and 310‐helical analogs. © 2012 Wiley Periodicals, Inc.
OBGMX: A web‐based generator of GROMACS topologies for molecular and periodic systems using the universal force field
Authors: Garberoglio Giovanni
Published: June 2012

OBGMX is a web service providing topologies for the GROMACS molecular dynamics software package according to the Universal Force Field, as implemented in the Open Babel package. OBGMX can deal with molecular and periodic systems. The geometrical parameters appearing in the potential energy functions for the bonded interactions can be set to those measured in the input configuration. The performance of OBGMX in reproducing the structure of periodic systems is analyzed by calculating the root mean‐squared displacements of optimized configurations of a large set of metal–organic frameworks. OBGMX is available at http://software‐lisc.fbk.eu/obgmx/. © 2012 Wiley Periodicals, Inc.
Over‐sulfated chondroitin sulfate Derivatives induce osteogenic differentiation of hMSC independent of BMP‐2 and TGF‐β1 signalling
Authors: Büttner Marianne , Möller Stephanie , Keller Mario , Huster Daniel , Schiller Jürgen , Schnabelrauch Matthias , Dieter Peter , Hempel Ute
Published: June 2012

Natural glycosaminoglycans (GAGs) and chemically modified GAG derivatives are known to support osteogenic differentiation of mesenchymal stromal cells (MSC). This effect has mainly been described to be mediated by increasing the effectiveness of bone anabolic growth factors such as bone morphogenetic proteins (BMPs) due to the binding and presentation of the growth factor or by modulating its signal transduction pathway. In the present study, the influence of chondroitin sulfate (CS) and two chemically over‐sulfated CS derivatives on osteogenic differentiation of human mesenchymal stromal cells (hMSC) and on BMP‐2 and transforming growth factor β1 (TGF‐β1) signalling was investigated. Over‐sulfated CS derivatives induced an increase of tissue non‐specific alkaline phosphatase (TNAP) activity and calcium deposition, whereas collagen synthesis was slightly decreased. The BMP‐2‐induced Smad1/5 activation was inhibited in the presence of over‐sulfated CS derivatives leading to a loss of BMP‐2‐induced TNAP activity and calcium deposition. In contrast, the TGF‐β1‐induced activation of Smad2/3 and collagen synthesis were not affected by the over‐sulfated CS derivatives. BMP‐2 and TGF‐β1 did not activate the extracellular signal‐regulated kinase 1/2 or mitogen‐activated protein kinase p38 in hMSC. These data suggest that over‐sulfated CS derivatives themselves are able to induce osteogenic differentiation, probably independent of BMP‐2 and TGF‐β1 signalling, and offer therefore an interesting approach for the improvement of bone healing. J. Cell. Physiol. 228: 330–340, 2013. © 2012 Wiley Periodicals, Inc.
Cyclooxygenase‐2 up‐regulates CCR7 expression via AKT‐mediated phosphorylation and activation of Sp1 in breast cancer cells
Authors: Chuang Chun‐Wei , Pan Mei‐Ren , Hou Ming‐Feng , Hung Wen‐Chun
Published: June 2012

Up‐regulation of cyclooxygenase‐2 (COX‐2) is frequently found in human cancers and is significantly associated with tumor metastasis. Our previous results demonstrate that COX‐2 and its metabolite prostaglandin E2 (PGE2) stimulate the expression of CCR7 chemokine receptor via EP2/EP4 receptors to promote lymphatic invasion in breast cancer cells. In this study, we address the underlying mechanism of COX‐2/PGE2‐induced CCR7 expression. We find that COX‐2/PGE2 increase CCR7 expression via the AKT signaling pathway in breast cancer cells. Promoter deletion and mutation assays identify the Sp1 site located at the −60/−57 region of CCR7 gene promoter is critical for stimulation. Chromatin immunoprecipitation (ChIP) assay confirms that in vivo binding of Sp1 to human CCR7 promoter is increased by COX‐2 and PGE2. Knockdown of Sp1 by shRNA reduces the induction of CCR7 by PGE2. We demonstrate for the first time that AKT may directly phosphorylate Sp1 at S42, T679, and S698. Phosphorylation‐mimic Sp1 protein harboring S42D, T679D, and S698D mutation strongly activates CCR7 expression. In contrast, change of these three residues to alanine completely blocks the induction of CCR7 by PGE2. Pathological investigation demonstrates that CCR7 expression is strongly associated with phospho‐AKT and Sp1 in 120 breast cancer tissues. Collectively, our results demonstrate that COX‐2 up‐regulates CCR7 expression via AKT‐mediated phosphorylation and activation of Sp1 and this pathway is highly activated in metastatic breast cancer. J. Cell. Physiol. 228: 341–348, 2013. © 2012 Wiley Periodicals, Inc.
Preeclampsia‐associated stresses activate Gadd45a signaling and sFlt‐1 in placental explants
Authors: Xiong Yali , Liebermann Dan A. , Holtzman Eliezer J. , Jeronis Stacey , Hoffman Barbara , Geifman‐Holtzman Ossie
Published: June 2012

Accumulating evidence suggests that placental stresses during pregnancy can play an important role in the pathogenesis of preeclampsia. A common signal pathway that senses and converts placental stresses into intracellular stress response may be contributing to this pathology. Based on our previous findings, we extended our investigation to establish that Gadd45a stress signaling regulates sFlt‐1 levels, particularly in placenta, when exposed to various preeclampsia‐associated stresses including AT‐1 receptor agonist (Angiotensin II), hypoxia, and inflammatory cytokines. Using a placental explant model, we found that Gadd45a was induced in response to all the preeclampsia stresses stated above. Although stress induced Gadd45a was associated with the activation of its downstream effectors phospho‐p38 and phospho‐JNK, the subsequent regulation of sFlt‐1 levels occurred through either one of these effectors, but not both. These observations indicate that Gadd45a signaling may work as a hub connecting placental stresses and the pathogenesis of preeclampsia. It also provides evidence to justify testing the role of Gadd45 in the etiology of preeclampsia using in vivo mouse (i.e., Gadd45a null mice) models. J. Cell. Physiol. 228: 362–370, 2013. © 2012 Wiley Periodicals, Inc.
Impaired pulmonary defense against Pseudomonas aeruginosa in VEGF gene inactivated mouse lung
Authors: Breen Ellen C. , Malloy Jaret L. , Tang Kechun , Xia Feng , Fu Zhenxing , Hancock Robert E.W. , Overhage Joerg , Wagner Peter D. , Spragg Roger G.
Published: June 2012

Repeated bacterial and viral infections are known to contribute to worsening lung function in several respiratory diseases, including asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD). Previous studies have reported alveolar wall cell apoptosis and parenchymal damage in adult pulmonary VEGF gene ablated mice. We hypothesized that VEGF expressed by type II cells is also necessary to provide an effective host defense against bacteria in part by maintaining surfactant homeostasis. Therefore, Pseudomonas aeruginosa (PAO1) levels were evaluated in mice following lung‐targeted VEGF gene inactivation, and alterations in VEGF‐dependent type II cell function were evaluated by measuring surfactant homeostasis in mouse lungs and isolated type II cells. In VEGF‐deficient lungs increased PAO1 levels and pro‐inflammatory cytokines, TNFα and IL‐6, were detected 24 h after bacterial instillation compared to control lungs. In vivo lung‐targeted VEGF gene deletion (57% decrease in total pulmonary VEGF) did not alter alveolar surfactant or tissue disaturated phosphatidylcholine (DSPC) levels. However, sphingomyelin content, choline phosphate cytidylyltransferase (CCT) mRNA, and SP‐D expression were decreased. In isolated type II cells an 80% reduction of VEGF protein resulted in decreases in total phospholipids (PL), DSPC, DSPC synthesis, surfactant associated proteins (SP)‐B and ‐D, and the lipid transporters, ABCA1 and Rab3D. TPA‐induced DSPC secretion and apoptosis were elevated in VEGF‐deficient type II cells. These results suggest a potential protective role for type II cell‐expressed VEGF against bacterial initiated infection. J. Cell. Physiol. 228: 371–379, 2013. © 2012 Wiley Periodicals, Inc.
HGF regulates the activation of TGF‐β1 in rat hepatocytes and hepatic stellate cells
Authors: Narmada Balakrishnan Chakrapani , Chia Ser‐Mien , Tucker‐Kellogg Lisa , Yu Hanry
Published: June 2012

Hepatocyte growth factor (HGF) ameliorates experimental liver fibrosis through many mechanisms, including degradation of accumulated collagen and decreased expression of fibrotic genes. Investigating an upstream mechanism in which HGF could decrease many fibrotic effectors, we asked whether HGF regulates activation of the fibrotic cytokine transforming growth factor‐beta 1 (TGF‐β1). Specifically, we tested whether HGF decreases the levels of active TGF‐β1, and whether such decrease depends on the predominantly hepatocyte‐secreted protease plasmin, and whether it depends on the TGF‐β1 activator thrombospondin‐1 (TSP‐1). With hepatocyte monocultures, we found HGF‐induced hepatocyte proliferation did increase total levels of plasmin, while decreasing gene expression of fibrotic markers (PAI‐1, TGF‐β1, and TIMP‐2). With in vitro models of fibrotic liver (HSC‐T6 hepatic stellate cells, or co‐cultures of HSC‐T6 and hepatocytes), we found high levels of fibrosis‐associated proteins such as TSP‐1, active TGF‐β1, and Collagen I. HGF treatment on these fibrotic cultures stimulated plasmin levels; increased TSP‐1 protein cleavage; and decreased the levels of active TGF‐β1 and Collagen I. When plasmin was blocked by the inhibitor aprotinin, HGF could no longer decrease TGF‐β1 activation and Collagen I. Meanwhile, the TSP‐1‐specific peptide inhibitor, LSKL, reduced TGF‐β1 to the same level as in the HGF‐treated cultures; combining LSKL and HGF treatments caused no further decrease, suggesting that HGF affects the TSP‐1 dependent pathway of TGF‐β1 activation. Therefore, HGF can decrease TGF‐β1 activation and TGF‐β1‐dependent fibrotic markers, by stimulating hepatocytes to produce plasmin, and by antagonizing TSP‐1‐dependent activation of TGF‐β1. J. Cell. Physiol. 228: 393–401, 2013. © 2012 Wiley Periodicals, Inc.
Treatment of wastewater from acrylonitrile‐butadiene‐styrene (ABS) resin manufacturing by biological activated carbon (BAC)
Authors: Lai Bo , Zhou Yuexi , Yang Ping
Published: June 2012

Background: The wastewater originating from the production of acrylonitrile‐butadiene‐styrene (ABS) resin is a toxic and refractory industrial wastewater. The purpose of this work is to investigate the characteristics of adsorption and biodegradation of biological activated carbon (BAC) for ABS resin wastewater.

Results: More than 80% of chemical oxygen demand (COD), total organic carbon (TOC) and organic nitrogen (Org‐N) was removed after the 100th run in BAC with the help of bioregeneration, and the treatment efficiency of BAC was higher than that of adsorption and biodegradation alone. The initial Org‐N was mainly transformed into NH4+‐N, and the transform efficiency reached 65% after the 100th run. After bioregeneration, the COD and TOC removal efficiencies of BAC reactor reached 88.97% and 86.26%, respectively. The BAC had different bioregeneration efficiencies of 94.41, 64.82, 61.05 and 40.04% for 3, 3‐imminodipropiononitrile, 3, 3‐oxydipropiononitrile, α, α‐dimethyl‐benzylalcohol and acetophenone, respectively, which mainly resulted from the different polarity of the compounds.

Conclusion: BAC could protect microorganisms from shock loadings of toxic, refractory and complicated ABS resin wastewater. The mechanism of the organic pollutants removal by BAC consisted of three phases including adsorption, bioregeneration and stability. © 2012 Society of Chemical Industry
Extraction and recovery of pectic fragments from citrus processing waste for co–production with ethanol
Authors: Grohman Karel , Cameron Randall , Kim Yang , Widmer Wilbur , Luzio Gary
Published: June 2012

BACKGROUND: Approximately 0.7 − 1 × 106 dry tons of citrus processing waste (CPW) are produced annually in the United States. CPW is sold as animal feed but often the financial return does not exceed the production cost. Polysaccharides comprise 40% of the total dry matter of which pectin is the major component. CPW was steam treated to extract pectin fragments (PFs) as a value added co–product prior to fermentation of other sugars for biofuels production.

RESULTS: PFs were extracted in high yields, along with polymeric arabinans, galactans and arabinogalactans. The extracted polysaccharides ranged in size from small oligomers to polymers of ∼700 000 g mol−1. Acidified treatments led to greater fragmentation of water soluble polysaccharides, but did not enhance fragmentation of pectins to small oligomers (> 30 mer). Methylesterified PFs, arabinans and galactans were recovered by ethanol precipitation while demethylesterified PFs were recovered and purified by precipitation with dilute HCl.

CONCLUSION: Steam treatment of CPW provides for rapid, efficient fragmentation of protopectin into highly methylesterified PFs that could be recovered by precipitation. The steaming process for preparation of PFs is environmentally friendly. No toxic chemicals are introduced and the remaining CPW can be used in fermentations to produce ethanol and other compounds. © 2012 Society of Chemical Industry
Persistence of endodontic methacrylate‐based cement residues on dentin adhesive surface treated with different chemical removal protocols
Authors: Kuga Milton Carlos , Só Marcus Vinicius Reis , De Campos Edson Alves , Faria Gisele , Keine Kátia Cristina , Dantas Andrea Abi Rached , Faria‐ Norberto Batista
Published: June 2012

The aim of this study was to evaluate the persistence of methacrylate‐based cement residues on the dentin, after dentin surface cleaning with ethanol or acetone, with or without previous application of a dentin adhesive. Forty bovine crown fragments were obtained and the dentin surface was washed with 1.0 mL of 2.5% sodium hypochlorite (NaOCl), followed by 0.1 mL of 17% ethylenediaminetetraacetic acid application for 3 min, and final irrigation with 2.5% NaOCl. The specimens were air dried and resin‐based cement was rubbed onto the dentine surface with a microbrush applicator. In 20 specimens, previously to cement, a dentin adhesive was applied in all surfaces. After 15 min, the surface was scrubbed with a cotton pellet and moistened with ethanol or acetone, compounding the following groups: G1—99.5% ethanol and G2—acetone, without previous use of dentin adhesive; G3—99.5% ethanol and G4—acetone, with previous use of dentin adhesive. The dentin surface was scrubbed until the cement residues could not be visually detected. Sections were then processed for scanning electron microscopy and evaluated at 500× magnification and scores were attributed to each image according to the area covered by residual sealer, and data were subjected to Kruskal–Wallis at 5% significance. The lower residue presence was observed in G3 (P = 0.005). All surface presented cement residues when acetone was used as cleaning solution (P = 0.0005). The cleaning solutions were unable to completely remove the cement residues from both surfaces. The ethanol used after previous application of the dentin adhesive promoted the lower presence of residues. Microsc. Res. Tech. 2012. © 2012 Wiley Periodicals, Inc.
Nanoscale imaging of morphological changes of umbilical cord in pre‐eclampsia
Authors: Kim Kyung Sook , Kim Young‐Sun , Lim Jin Ik , Jung Min Hyung , Park Hun‐Kuk
Published: June 2012

It is known that pre‐eclampsia affects the structure of the umbilical cord including changes in diameter and wall thickness. In this work, the morphological changes of umbilical cords associated with pre‐eclampsia were investigated using scanning electron microscopy (SEM) and atomic force microscopy (AFM). The SEM images showed the overall structural changes in the umbilical cord, and the AFM imaged the surface of the cord in the nanometer range. The amount of Wharton's jelly was reduced in the cords of pre‐eclampsia patients and it was holed along the boundary. Compared to a normal pregnancy, the surface of a pre‐eclampsia cord was relatively smooth. In all components (Wharton's jelly, veins, and arteries), the values for surface roughness, Sa (average value of the roughness), Sq (root mean square), and Sz (peak to peak value), were smaller than those of the control (P < 0.05). Especially, the values for Sa of veins were ∼fourfold less than those of the controls (P < 0.05). In pre‐eclamptic cords, the amount of elastin in veins was increased while that of the artery was decreased. Microsc. Res. Tech. 2012. © 2012 Wiley Periodicals, Inc.
Examining the Role of Similarity Coefficients and the Value of Behavioural Themes in Attempts to Link Serial Arson Offences
Authors: Ellingwood Holly , Mugford Rebecca , Bennell Craig , Melnyk Tamara , Fritzon Katarina
Published: June 2012

When relying on crime scene behaviours to link serial crimes, linking accuracy may be influenced by the measure used to assess across‐crime similarity and the types of behaviours included in the analysis. To examine these issues, the present study compared the level of linking accuracy achieved by using the simple matching index (S) to that of the commonly used Jaccard's coefficient (J) across themes of arson behaviour. The data consisted of 42 crime scene behaviours, separated into three behavioural themes, which were exhibited by 37 offenders across 114 solved arsons. The results of logistic regression and receiver operating characteristic analysis indicate that, with the exception of one theme where S was more effective than J at discriminating between linked and unlinked crimes, no significant differences emerged between the two similarity measures. In addition, our results suggest that thematically unrelated behaviours can be used to link crimes with the same degree of accuracy as thematically related behaviours, potentially calling into the question the importance of theme‐based approaches to behavioural linkage analysis. Copyright © 2012 John Wiley & Sons, Ltd.
Dnmt3a regulates both proliferation and differentiation of mouse neural stem cells
Authors: Wu Zhourui , Huang Kevin , Yu Juehua , Le Thuc , Namihira Masakasu , Liu Yupeng , Zhang Jun , Xue Zhigang , Cheng Liming , Fan Guoping
Published: June 2012

DNA methylation is known to regulate cell differentiation and neuronal function in vivo. Here we examined whether deficiency of a de novo DNA methyltransferase, Dnmt3a, affects in vitro differentiation of mouse embryonic stem cells (mESCs) to neuronal and glial cell lineages. Early‐passage neural stem cells (NSCs) derived from Dnmt3a‐deficient ESCs exhibited a moderate phenotype in precocious glial differentiation compared with wild‐type counterparts. However, successive passaging to passage 6 (P6), when wild‐type NSCs become gliogenic, revealed a robust phenotype of precocious astrocyte and oligodendrocyte differentiation in Dnmt3a−/− NSCs, consistent with our previous findings in the more severely hypomethylated Dnmt1−/− NSCs. Mass spectrometric analysis revealed that total levels of methylcytosine in Dnmt3a−/− NSCs at P6 were globally hypomethylated. Moreover, the Dnmt3a−/− NSC proliferation rate was significantly increased compared with control from P6 onward. Thus, our work revealed a novel role for Dnmt3a in regulating both the timing of neural cell differentiation and the cell proliferation in the paradigm of mESC‐derived‐NSCs. © 2012 Wiley Periodicals, Inc.
Standardized extract of Bacopa monniera (BESEB CDRI‐08) attenuates contextual associative learning deficits in the aging rat's brain induced by D‐galactose
Authors: Prisila Dulcy Charles , Singh Hemant K. , Preethi Jayakumar , Emmanuvel Rajan Koilmani
Published: June 2012

In this study, we examined the neuroprotective effect of standardized Bacopa monniera extract (BME: BESEB CDRI‐08) against the D‐galactose (D‐gal)‐induced brain aging in rats. Experimental groups were subjected to contextual‐associative learning task. We found that the administration of BME in the D‐gal‐treated group attenuated contextual‐associative learning deficits; the individuals showed more correct responses and retrieved the reward with less latency. Subsequent analysis showed that the BME administration significantly decreased advance glycation end product (AGE) in serum and increased the activity of antioxidant response element (ARE) and the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), and nuclear transcription factor NF‐E2‐related factor 2 (Nrf2), accompanied by a reduction in the level of serotonin (5‐HT) in the hippocampus. The BME treatment also reversed D‐gal‐induced brain aging by upregulating the levels of the presynaptic proteins synaptotagmin I (SYT1) and synaptophysin (SYP) and the postsynaptic proteins Ca2+/calmodulin dependent protein kinase II (αCaMKII) and postsynaptic density protein‐95 (PSD‐95) in the hippocampus during synaptic plasticity. A significant finding is that the D‐gal‐ + BME‐treated rats exhibited more correct responses in contextual‐associative learning than D‐gal alone‐treated rats. Our findings suggest that BME treatment attenuates D‐gal‐induced brain aging and regulates the level of antioxidant enzymes, Nrf2 expression, and the level of 5‐HT, which was accompanied by concomitantly increased levels of synaptic proteins SYT1, SYP, αCaMKII, p‐αCaMKII, and PSD‐95. © 2012 Wiley Periodicals, Inc.
Transforming growth factor‐β stimulates β amyloid uptake by microglia through Smad3‐dependent mechanisms
Authors: Tichauer Juan E. , von Bernhardi Rommy
Published: June 2012

Inflammatory cytokines and β amyloid (Aβ) induce activation of glial cells, leading to both protective and deleterious changes that are relevant for the pathogenesis of Alzheimer disease (AD). We have shown that astrocytes downregulate microglial cell cytotoxic activation through secretion of transforming growth factor‐β (TGFβ1), and there is evidence that TGFβ1 modifies Aβ removal through the modulation of microglia. However, inflammatory activation of microglia is increased and Aβ clearance is reduced in AD patients, regardless of the fact that TGFβ1 is increased in their nervous system. We propose that changes in TGFβ Smad3 signal transduction could modify the regulation mediated by TGFβ1. Here we evaluated the participation of the TGFβ Smad3 pathway in regulation of the expression pattern of scavenger receptors (SR) and activation of microglia through nitric oxide (NO·) secretion and phagocytosis of Aβ. We found that TGFβ1 increased SR‐A by 2.4‐fold and decreased SR‐BI expression by 79% at 48 hr, whereas it did not change SR‐MARCO or CD36 expression. In addition, we observed a 51% increase of Aβ uptake and an 83% decrease of NO· production induced by lipopolysaccharide in microglial cell cultures. Increased expression of SR‐A, phagocytosis, and downregulation of NO· by TGFβ1 were prevented by the inhibition of the TGFβ Smad3 pathway. Our results indicate that the modulation of microglial cell activation by TGFβ1, leading to increased clearance of Aβ and reduced cytotoxicity, is at least partially mediated by the Smad pathway. © 2012 Wiley Periodicals, Inc.
Altered global and regional brain mean diffusivity in patients with obstructive sleep apnea
Authors: Kumar Rajesh , Chavez Alexa S. , Macey Paul M. , Woo Mary A. , Yan‐Go Frisca L. , Harper Ronald M.
Published: June 2012

Obstructive sleep apnea (OSA) is a common and progressive disorder accompanied by severe cardiovascular and neuropsychological sequelae, presumably induced by brain injury resulting from the intermittent hypoxia and cardiovascular processes accompanying the syndrome. However, whether the predominant brain tissue pathology is acute or chronic in newly‐diagnosed, untreated OSA subjects is unclear; this assessment is essential for revealing pathological processes. Diffusion tensor imaging (DTI)‐based mean diffusivity (MD) procedures can detect and differentiate acute from chronic pathology and may be useful to reveal processes in the condition. We collected four DTI series from 23 newly‐diagnosed, treatment‐naïve OSA and 23 control subjects, using a 3.0‐Tesla magnetic resonance imaging scanner. Mean diffusivity maps were calculated from each series, realigned, averaged, normalized to a common space, and smoothed. Global brain MD values for each subject were calculated using normalized MD maps and a global brain mask. Mean global brain MD values and smoothed MD maps were compared between groups by using analysis of covariance (covariate: age). Mean global brain MD values were significantly reduced in OSA compared with controls (P = 0.01). Multiple brain sites in OSA, including medullary, cerebellar, basal ganglia, prefrontal and frontal, limbic, insular, cingulum bundle, external capsule, corpus callosum, temporal, occipital, and corona radiata regions showed reduced regional MD values compared with controls. The results suggest that global brain MD values are significantly reduced in OSA, with certain regional sites especially affected, presumably a consequence of axonal, glial, and other cell changes in those areas. The findings likely represent acute pathological processes in newly‐diagnosed OSA subjects. © 2012 Wiley Periodicals, Inc.
Signalling routes and developmental regulation of group I metabotropic glutamate receptors in rat auditory midbrain neurons
Authors: Martinez‐Galan Juan R. , Perez‐Martinez Francisco C. , Juiz Jose M.
Published: June 2012

Group I metabotropic glutamate receptors (mGluRs) are linked to intracellular Ca2+ signalling and play important roles related to synaptic plasticity and development. In neurons from the central nucleus of the inferior colliculus (CIC), the activation of these receptors evokes large [Ca2+]i responses. By using optical imaging of the fluorescent Ca2+‐sensitive dye Fura‐2, we have explored which [Ca2+]i routes are triggered by group I mGluR activation in young CIC neurons and whether mGluR‐induced [Ca2+]i responses are regulated during postnatal development. In addition, real‐time quantitative RT‐PCR was used to study the developmental expression of both group I mGluR subtypes, mGluR1 and mGluR5. Application of DHPG, a specific agonist of group I mGluRs, was used on CIC slices from young rats to elicit [Ca2+]i responses. A majority of responses consisted of an initial thapsigargin‐sensitive Ca2+ peak, related to store depletion, followed by a plateau phase, sensitive to the store‐operated Ca2+ entry blocker 2‐APB. During postnatal development, from P6 to P17, DHPG‐induced [Ca2+]i responses changed. The largest Ca2+ responses were reached at P6, whereas lower peak and plateau responses were found after hearing onset, at P13–P14 and P17. qRT‐PCR analysis also revealed important differences in the expression of both mGluR1 and mGluR5 subtypes during development, with the highest levels of both subtypes at P7 and a developmental decrease of both transcripts. Our results suggest both intra‐ and extracellular routes for [Ca2+]i increases linked to group I mGluRs in CIC neurons and a regulation of group I mGluR activity and expression during auditory development. © 2012 Wiley Periodicals, Inc.
Hypoactivity of the central dopaminergic system and autistic‐like behavior induced by a single early prenatal exposure to lipopolysaccharide
Authors: Kirsten Thiago B. , Chaves‐Kirsten Gabriela P. , Chaible Lucas M. , Silva Ana C. , Martins Daniel O. , Britto Luiz R.G. , Dagli Maria L.Z. , Torrão Andrea S. , Palermo‐Neto João , Bernardi Maria M.
Published: June 2012

The aim of the present study was to evaluate the behavioral patterns associated with autism and the prevalence of these behaviors in males and females, to verify whether our model of lipopolysaccharide (LPS) administration represents an experimental model of autism. For this, we prenatally exposed Wistar rats to LPS (100 μg/kg, intraperitoneally, on gestational day 9.5), which mimics infection by gram‐negative bacteria. Furthermore, because the exact mechanisms by which autism develops are still unknown, we investigated the neurological mechanisms that might underlie the behavioral alterations that were observed. Because we previously had demonstrated that prenatal LPS decreases striatal dopamine (DA) and metabolite levels, the striatal dopaminergic system (tyrosine hydroxylase [TH] and DA receptors D1a and D2) and glial cells (astrocytes and microglia) were analyzed by using immunohistochemistry, immunoblotting, and real‐time PCR. Our results show that prenatal LPS exposure impaired communication (ultrasonic vocalizations) in male pups and learning and memory (T‐maze spontaneous alternation) in male adults, as well as inducing repetitive/restricted behavior, but did not change social interactions in either infancy (play behavior) or adulthood in females. Moreover, although the expression of DA receptors was unchanged, the experimental animals exhibited reduced striatal TH levels, indicating that reduced DA synthesis impaired the striatal dopaminergic system. The expression of glial cell markers was not increased, which suggests that prenatal LPS did not induce permanent neuroinflammation in the striatum. Together with our previous finding of social impairments in males, the present findings demonstrate that prenatal LPS induced autism‐like effects and also a hypoactivation of the dopaminergic system. © 2012 Wiley Periodicals, Inc.
Deficiency of ganglioside GM1 correlates with Parkinson's disease in mice and humans
Authors: Wu Gusheng , Lu Zi‐Hua , Kulkarni Neil , Ledeen Robert W.
Published: June 2012

Several studies have successfully employed GM1 ganglioside to treat animal models of Parkinson's disease (PD), suggesting involvement of this ganglioside in PD etiology. We recently demonstrated that genetically engineered mice (B4galnt1−/−) devoid of GM1 acquire characteristic symptoms of this disorder, including motor impairment, depletion of striatal dopamine, selective loss of tyrosine hydroxylase‐expressing neurons, and aggregation of α‐synuclein. The present study demonstrates similar symptoms in heterozygous mice (HTs) that express only partial GM1 deficiency. Symptoms were alleviated by administration of L‐dopa or LIGA‐20, a membrane‐permeable analog of GM1 that penetrates the blood–brain barrier and accesses intracellular compartments. Immunohistochemical analysis of paraffin sections from PD patients revealed significant GM1 deficiency in nigral dopaminergic neurons compared with age‐matched controls. This was comparable to the GM1 deficiency of HT mice and suggests that GM1 deficiency may be a contributing factor to idiopathic PD. We propose that HT mice with partial GM1 deficiency constitute an especially useful model for PD, reflecting the actual pathophysiology of this disorder. The results point to membrane‐permeable analogs of GM1 as holding promise as a form of GM1 replacement therapy. © 2012 Wiley Periodicals, Inc.
Immunohistochemical study of semicarbazide‐sensitive amine oxidase/vascular adhesion protein‐1 in the hippocampal vasculature: Pathological synergy of Alzheimer's disease and diabetes mellitus
Authors: Valente Tony , Gella Alejandro , Solé Montse , Durany Núria , Unzeta Mercedes
Published: June 2012

Semicarbazide‐sensitive amine oxidase/vascular adhesion protein‐1 (SSAO/VAP‐1) is involved in vascular endothelial damage as well as in the vascular degeneration underlying diabetes mellitus and Alzheimer's disease (AD). Recent evidence suggests that classic pathological features of AD are more pronounced in diabetic mellitus patients. To investigate the expression and distribution of SSAO/VAP‐1 in the two pathologies, we have performed an immunohistochemical study in human hippocampal vessels of AD, AD with diabetic mellitus (ADD), diabetic mellitus (DM), and nondemented (ND) patients. The present results demonstrate major vessel accumulation of both SSAO/VAP‐1 and amyloid‐β immunolabeling intensity in ADD compared with AD patients. Interestingly, nearly damaged vessels with high levels of SSAO/VAP‐1 also showed increased oxidative damage markers (AGE, RAGE, and SOD‐1) and glial activation (GFAP and HLA). Overall, this work suggests that high vascular SSAO/VAP‐1 levels in human hippocampus may contribute to vascular degeneration, which can explain the severe progression in patients with both pathologies. © 2012 Wiley Periodicals, Inc.
Calpain inhibition attenuated morphological and molecular changes in skeletal muscle of experimental allergic encephalomyelitis rats
Authors: Park Sookyoung , Nozaki Kenkichi , Guyton M. Kelly , Smith Joshua A. , Ray Swapan K. , Banik Naren L.
Published: June 2012

Muscle weakness and atrophy are important manifestations of multiple sclerosis (MS). To investigate the pathophysiological mechanisms of skeletal muscle change in MS, we induced experimental autoimmune encephalomyelitis (EAE) in Lewis male rats and examined morphological and molecular changes in skeletal muscle. We also treated EAE rats with calpepetin, a calpain inhibitor, to examine its beneficial effects on skeletal muscle damage. Morphological changes in muscle tissue of EAE rats included smaller and irregularly shaped muscle fibers and fibrosis. Western blot analysis demonstrated increased calpain:calpastatin ratio, inflammation‐related transcription factors (nuclear factor‐κB:inhibitor of κB α ratio), and proinflammatory enzymes (cyclooxygenase‐2). TUNEL‐positive myonuclei in skeletal muscle cells of EAE rats indicated cell death. In addition, markers of apoptotic cell death (Bax:Bcl‐2 ratio and caspase‐12 protein levels) were elevated. Expression of muscle‐specific ubiquitin ligases (muscle atrophy F‐box and muscle ring finger protein 1), was upregulated in muscle tissue of EAE‐vehicle animals. Both prophylactic and therapeutic treatment with calpeptin partially attenuated muscle changes noted in EAE animals. These results indicate that morphological and molecular changes including apoptotic cell death and protein breakdown develop in skeletal muscle of EAE animals and that these changes can be reversed by calpain inhibition. © 2012 Wiley Periodicals, Inc.
The effect of induced yellowing on the physicochemical properties of specialty rice
Authors: Bryant Rolfe J , Yeater Kathleen M , Belefant‐Miller Helen
Published: June 2012

BACKGROUND: Postharvest yellowing (PHY) of rice kernels can be a major problem in the rice industry. This is especially true with high‐valued specialty rice, because profit loss will be greater. The objective of this work was to determine whether a significant change occurs in the physicochemical properties (apparent amylose and protein concentrations, viscosity profile and gelatinisation temperature) as a result of induced PHY.

RESULTS: In this study, four specialty rices (Basmati, Jasmine, Arborio and Sushi) were yellowed using a laboratory method. PHY increased apparent amylose concentration. It also significantly increased onset and peak gelatinisation temperatures. However, peak, breakdown and setback Rapid ViscoAnalyzer viscosities were decreased by PHY. Trough viscosity for Basmati and Jasmine decreased, whereas it increased for Arborio. Moisture and protein concentrations were unchanged by the yellowing process. Attempts to rehydrate the kernels after induced PHY caused them to fracture, thus making them unsuitable for their intended purpose.

CONCLUSION: This study indicates that rice that has been subjected to PHY shows a reduction not only in appearance but also in cooking and processing quality, decreasing its value. However, the changes differed for each rice type, with Jasmine being affected the least. Published 2012 by John Wiley & Sons, Ltd.
Selenium increases chlorogenic acid, chlorophyll and carotenoids of Lycium chinense leaves
Authors: Dong Jing Z , Wang Ying , Wang Shu H , Yin Ling P , Xu Guan J , Zheng Cheng , Lei Can , Zhang Ming Z
Published: June 2012

BACKGROUND: Leaves of Lycium chinense L. are widely used in traditional Chinese medicine and as functional food in China and south‐east Asia. Polyphenols are important active compounds in leaves of L. chinense L, but their compositions are still not very clear. Selenium has been reported to increase some components of plants. In this study, the composition of polyphenols of L. chinense leaves were analysed, and the effects of selenium on the polyphenols and other components were studied.

RESULTS: The main polyphenols were identified as rutin, chlorogenic acid, quercetin, kaempferol and apigenin‐7‐O‐(6′‐O‐acetyl) glucose‐rhamnose. Chlorogenic acid showed the highest average content of 78.36 g kg−1. Rutin, quercetin and kaempferol were determined at low contents from 3.85 g kg−1 to 7.08 g kg−1. Correlation coefficients between selenium and chlorogenic acid, chlorophyll a, chlorophyll b and carotenoids were: R2 = 0.963 (P = 0.002), 0.943 (P = 0.005), 0.957 (P = 0.003) and 0.943 (P = 0.005), respectively. Selenium (0.01–0.05 g kg−1) significantly increased chlorogenic acid, chlorophyll and carotenoids by 200–400% and reduced rutin by 400–900%.

CONCLUSION: L. chinense can be an alternative source of chlorogenic acid. Selenium significantly increased chlorogenic acid, chlorophyll a, chlorophyll b and carotenoids, hence increasing the medicinal value of L. chinense leaves. Rutin, quercetin, kaempferol and apigenin‐7‐O‐(6′‐O‐acetyl) glucose‐rhamnose proved to be not significantly influenced by selenium. Copyright © 2012 Society of Chemical Industry
Radionuclide therapy of adrenal tumors
Authors: Carrasquillo Jorge A. , Pandit‐Taskar Neeta , Chen Clara C.
Published: June 2012

Adrenal tumors arising from chromaffin cells will often accumulate radiolabeled metaiodobenzylguanidine (MIBG) and thus are amenable to therapy with I‐131 MIBG. More recently, therapy studies have targeted the somatostatin receptors using Lu‐177 or Y‐90 radiolabeled somatostatin analogs. Because pheochromocytoma (PHEO)/paraganglioma (PGL) and neuroblastoma (NB), which often arise from the adrenals, express these receptors, clinical trials have been performed with these reagents. We will review the experience using radionuclide therapy for targeting PHEO/PGL and NBs. J. Surg. Oncol. 2012; 106:632–642. © 2012 Wiley Periodicals, Inc.