bluuebunny/crossref_metadata_2025 huggingface dataset:
Supramolecular ferric porphyrins and a cyclodextrin dimer as antidotes for cyanide poisoning
Authors: Yamagiwa T , Kawaguchi AT , Saito T , Inoue S , Morita S , Watanabe K , Kitagishi H , Koji K , Inokuchi S
Published: August 2013

Objectives:

This study aimed to evaluate the antidotal effect of a newly developed supramolecular complex, ferric porphyrins and a cyclodextrin dimer (FeIIIPIm3CD), that possess a higher binding constant and quicker binding rate to cyanide ions than those of hydroxocobalamin (OHCbl) in the presence of serum protein.

Methods:

First, in vitro cytochrome activity and cell viability were evaluated in murine fibroblast cells cultured with various doses of FeIIIPIm3CD and potassium cyanide (KCN). Next, BALB/c mice were pretreated with intravenous OHCbl (0.23 mmol/kg), FeIIIPIm3CD (0.23 mmol/kg), or saline and then received KCN (lethal dose 100% (LD100): 0.23 mmol/kg) through a stomach tube. Finally, as a resuscitation model, KCN-induced apnea was treated with a bolus injection of an equimolar dose of antidotes followed by a slow infusion of the same reagent.

Results:

FeIIIPIm3CD showed dose-dependent antidotal effects in vitro. Pretreatment with FeIII PIm3CD prevented KCN-induced apnea significantly better than OHCbl. Resuscitation with FeIIIPIm3CD resulted in an earlier resumption of respiration than that seen with OHCbl. However, 24-h survival was similar among the treatments (FeIIIPIm3CD, nine of nine mice; OHCbl, eight of nine mice).

Conclusion:

FeIIIPIm3CD exerted significant antidotal effects on cyanide toxicity in vitro and in vivo, with a potency equal in the mortality of cyanide-poisoned mice or superior in the respiratory status during an acute phase to those of OHCbl.
Association between endothelial nitric oxide synthase gene polymorphism (-786T>C) and interleukin-6 in acute coronary syndrome
Authors: Piccoli JCE , Manfredini V , Faoro D , Farias FM , Bodanese LC , Bogo MR
Published: August 2013

Atherosclerosis is morphologically an inflammatory disease, where endothelial dysfunction plays a key role in all the stages. The nitric oxide (NO) synthase 3 ( NOS3) gene is responsible for the synthesis of endothelial NO synthase (eNOS) in humans and some genetic polymorphisms are considered “polymorphisms associated with risk” for the development of coronary artery diseases, such as acute coronary syndrome. Thus, the present study aimed to evaluate the influence of the -786T>C polymorphism of the eNOS gene on inflammatory and oxidative process. A prospective cohort study of 125 consecutive patients with clinical diagnosis of non-ST-elevation acute coronary syndromes was conducted. Patients were assessed using a standardized questionnaire. Blood samples were drawn to measure serum levels of high-sensitivity C-reactive protein, soluble CD40 ligand, interleukin-6 (IL-6), N-terminal prohormone of brain natriuretic peptide, immunoglobulin G antibodies against oxidized low-density lipoprotein. The genotypes for the -786T>C polymorphism in the 5′-flanking region of eNOS gene were determined. The -786C allele was found in 92 of 250 alleles (38.8%). No statistical association was observed between demographic and clinical characteristics and distribution of eNOS- 786T>C polymorphism. We found that -786CC was associated with lower levels of IL-6. No significant differences were observed between the distribution of -786T>C polymorphism and other investigated markers.
Dysregulation of the immune system in Aicardi-Goutières syndrome: another example in a TREX1-mutated patient
Authors: Olivieri I , Cattalini M , Tonduti D , Piana R La , Uggetti C , Galli J , Meini A , Tincani A , Moratto D , Fazzi E , Balottin U , Orcesi S
Published: August 2013

Aicardi-Goutières syndrome (AGS) is a rare genetic encephalopathy characterized by neurological and extraneurological involvement. A clinical overlap between AGS and systemic lupus erythematosus (SLE) has been reported. We describe an AGS patient who developed autoimmune manifestations: thyroiditis, cANCA positivity, antiphospholipid antibodies and cerebral ischemia. This first description of antiphospholipid syndrome in a TREX1-mutated patient further expands the clinical spectrum of AGS. Although the clinical overlap with SLE may indicate common pathogenic mechanisms, the autoimmune manifestations in AGS are so extensive that we suggest they should be considered a clinical feature of the disease, rather than a sign of coexistent SLE.
Pseudocontingencies
Authors: Fiedler Klaus , Kutzner Florian , Vogel Tobias
Published: August 2013

The ability to extract statistical contingencies (e.g., between cause and effect, between response and feedback) is commonly presupposed as a basic module of adaptive behavior. In reality, however, stimulus input rarely contains the complete sets of correlated attributes required to assess the actual contingencies. Instead, cognitive inferences often rely on a base-rate-driven pseudocontingency rule, which links the more (or less) frequent level of one variable to the more (or less) frequent level of the other variable. Empirical evidence shows that logically unwarranted pseudocontingency inferences override genuine contingencies across many research paradigms. Although pseudocontingencies can be severely misleading, they also provide a useful proxy that accurately predicts existing contingencies most of the time.
Do Pigeons Gamble? I Wouldn’t Bet Against It
Authors: Zentall Thomas R. , Laude Jennifer R.
Published: August 2013

Human gambling generally involves suboptimal choice because the expected return is usually less than the investment. We have found that animals, too, choose suboptimally under similar choice conditions. Pigeons, like human gamblers, show an impaired ability to objectively assess overall probabilities and amounts of reinforcement when a rare, high-value outcome (analogous to a jackpot in human gambling) is presented in the context of more frequently occurring losses. More specifically, pigeons prefer a low-probability, high-reward outcome over a guaranteed low-reward outcome with a higher overall value. Furthermore, manipulations assumed to increase impulsivity (pigeons maintained at higher levels of motivation for food and pigeons housed in individual cages) result in increased suboptimal choice. They do so presumably because they function to increase attraction to the signal for the low-probability, high-reward outcomes rather than consider the more global probability of reinforcement associated with each alternative.
What Role for Multilateral Development Banks in Project Finance? Some Thoughts from the Rift Valley Railways in Kenya and Uganda
Authors: Mutambatsere E. , Nalikka A. , Pal M. , Vencatachellum D.
Published: August 2013

This case study uses primary evidence from the Rift Valley Railways concession—a complex multinational rail concession originating from Mombasa (Kenya) and to Kampala (Uganda)—to discuss strategic roles of multilateral development banks in infrastructure project finance. We find that multilateral development banks were uniquely positioned to play the roles of advisor, honest broker, guarantor and financier required in this transaction. However, we document a number of shortcomings in execution which adversely affected the performance of the concession. First, procurement flaws resulted in the choice of an under-qualified lead investor, and subsequent non-performance of the concessionaire. Second, there was failure to ensure compliance with loan disbursement pre-conditions. Third, governments had unrealistic expectations about the concessionaire’s capacity to improve the railway’s performance and make major capital investments. Extensive due diligence on the lead investor prior to concession award could have circumvented concession restructuring. As investors become more interested in opportunities in Africa, more entities should provide advisory services to African countries. However, such entities should have adequate resources and capacity to remain engaged over a long period.
Scenario of Viability Gap Funding (VGF) Concept in Indian Infrastructure Projects
Authors: Maniar Hiren
Published: August 2013

Infrastructure is a key area since it provides the main thrust and impetus area in the growth of a developing nation like India. A major area of concern for sustaining the real gross domestic product (GDP) growth in India has been the lack of adequate infrastructure, which can support the growth process. The deplorably low levels of public investment have rendered India’s physical infrastructure incompatible with large increases in the national product. Clearly, without improving the rate of infrastructure investment, the expected growth rate of 9 per cent and above at best would remain modest. The Planning Commission of India has estimated that investment in infrastructure sector defined broadly to include road, rail, air and water transport, electric power, telecommunications, water supply and irrigation will need to be of the order of about ₹45 lakh crores or US$1.4 trillion during the 12th Five-year Plan period. India has one of the largest road networks in the world, aggregating around 33 lakh km; historically, the budgetary resources from the governments have been the major source of financing for infrastructure such as road projects in India. This article focuses on Viability Gap Funding (VGF) that has been used for financing of infrastructure projects and specially for road projects in India. The purpose of this article is to examine and analyse viability of the VGF scheme for Indian road projects by studying projects being covered under the VGF option.
Vaccine Perceptions Among Oregon Health Care Providers
Authors: Bean Sandra J. , Catania Joseph A.
Published: August 2013

Health care providers exert a significant influence on parental pediatric vaccination decisions. We conducted hour-long interviews with traditional and alternative health care providers in which we explored a range of associations between vaccination perceptions and practice. A key finding was that the Health Belief Model constructs of perceived susceptibility to and severity of either an illness or an adverse vaccine event partially explained health care provider (HCP) beliefs about the risks or benefits of vaccination, especially among alternative care providers. Low or high perceived susceptibility to a vaccine-preventable disease (VPD) or of the severity of a given VPD affects whether an HCP will promote or oppose pediatric vaccination recommendations. Beyond these perceptions, health and vaccination beliefs are affected by the contextual factors of personal experience, group norms, immunology beliefs, and beliefs about industry and government. Building powerful affective heuristics might be critical to balancing the forces that defeat good public health practices.
Vibration analysis of circular annular plates subjected to peripheral rotating transverse loads
Authors: Younesian Davood , Aleghafourian Mohammad Hosein , Esmailzadeh Ebrahim
Published: August 2013

Vibration of a hollow circular plate subjected to a rotating peripheral force is analytically studied in this paper. Closed-form solutions are developed in a series form for the plate deflection as well as the distributions of the strain and stress. The Galerkin approach is adopted as the solution method and a finite element model has also been developed. Computer simulations were performed to verify the model and solution methods were adopted. Close agreement is observed when comparing the numerical results with those obtained from the analytical technique. The acoustic pressure field is eventually obtained in front of the vibrating plate surface using the Rayleigh integral method. The solution procedure presented and the numerical results obtained can be extensively utilized in the noise source separation. This has always been a significant challenge in many engineering applications such as the railway wheel-rail dynamics or that of the automotive gear trains.
The Self-Regulation Model of Sexual Offending
Authors: Kingston Drew A. , Yates Pamela M. , Olver Mark E.
Published: August 2013

The self-regulation model (SRM) is a nine-phase, four-pathway offense process model designed specifically for sexual offenders that is now being applied to the treatment of this group in many settings and jurisdictions. In the present prospective study, we evaluated the validity and utility of the SRM in a sample of 275 adult male sexual offenders treated within the Correctional Service of Canada. Results indicated that participation in treatment resulted in moderate to large sized improvements from pretreatment to posttreatment on a dynamic risk assessment measure and several self-reported treatment targets. These changes were, in some cases, differentially associated with self-regulation pathways, suggesting that offense pathway is a clinically relevant variable when evaluating treatment change and in conceptualizing sexual offender treatment. In terms of outcome, individuals following the approach pathways, particularly the approach-automatic pathway, demonstrated higher failure rates than individuals following avoidant pathways. However, many of these differences were less pronounced when taking risk for recidivism into account. Implications of these findings for the effective assessment and rehabilitation of sexual offenders are discussed.
Using Immunotoxicity Information to Improve Cancer Risk Assessment for Polycyclic Aromatic Hydrocarbon Mixtures
Authors: Zaccaria Kimberly J. , McClure Peter R.
Published: August 2013

Estimating cancer risk from environmental mixtures containing polycyclic aromatic hydrocarbons (PAHs) is challenging. Ideally, each mixture would undergo toxicity testing to derive a cancer slope factor (CSF) for use in site-specific cancer risk assessments. However, this whole mixture approach is extremely costly in terms of finances, time, and animal usage. Alternatively, if an untested mixture is “sufficiently similar” to a well-characterized mixture with a CSF, the “surrogate” CSF can be used in risk assessments. We propose that similarity between 2 mixtures could be established using an in vitro battery of genotoxic and nongenotoxic tests. An observed association between carcinogenicity and immunosuppression of PAHs suggests that the addition of immune suppression assays may improve this battery. First, using published studies of benzo[a]pyrene (BaP) and other PAHs, we demonstrated a correlation between the derived immune suppression relative potency factors (RPFs) for 9 PAHs and their respective cancer RPFs, confirming observations published previously. Second, we constructed an integrated knowledge map for immune suppression by BaP based on the available mechanistic information. The map illustrates the mechanistic complexities involved in BaP immunosuppression, suggesting that multiple in vitro tests of immune suppression involving different processes, cell types, and tissues will have greater predictive value for immune suppression in vivo than a single test. Based on these observations, research strategies are recommended to validate a battery of in vitro immune suppression tests that, along with tests for genotoxic and other nongenotoxic modes of cancer action, could be used to establish “sufficient similarity” of 2 mixtures for site-specific cancer risk assessments.
One-Session Treatment of a Specific Phobia of Swallowing Pills
Authors: Davis Thompson E. , Reuther Erin T. , Rudy Brittany M.
Published: August 2013

This case study presents the treatment of a 23-year-old single White male with a specific phobia of swallowing and choking on pills. He presented for treatment as part of a larger treatment study for specific phobia and met criteria for a specific phobia, other type (swallowing pills), and social phobia. Treatment of the specific phobia involved One-Session Treatment and was conducted per Zlomke and Davis and Davis, Ollendick, and Öst. A posttreatment assessment 3 weeks after treatment and an 8-week follow-up assessment revealed significant improvements. At both assessments following treatment, clinician severity ratings on the Anxiety Disorders Inverview Schedule—Client (ADIS-IV) decreased, indicating no significant impairment, and the ADIS-IVs at those time periods indicated he no longer met criteria for a specific phobia. Improvements were also seen in the client’s self-reported fear, on his ratings of catastrophic cognitions, on a behavioral avoidance task, and in the comorbid social phobia symptoms.
Clopidogrel-Induced Recurrent Polyarthritis
Authors: Agrawal Sahil , Harburger Joseph , Stallings Gary , Agrawal Nikhil , Garg Jalaj
Published: August 2013

Clopidogrel is an oral thienopyridine and together with aspirin is a component of dual antiplatelet therapy for the prevention of stent thrombosis after intracoronary stent placement. The common adverse effects from its use are an increased risk of bleeding, neutropenia, and rash. Arthralgia and backache are also known to occur with its use. There have been case reports linking arthritis with the use of clopidogrel. We describe the case of a 64-year-old man who reported symptoms of fever and joint pains following initiation of therapy with clopidogrel. Acute-phase reactants were elevated. Laboratory and radiologic testing were unremarkable. Incidentally, he reported experiencing a similar arthritis after he received a loading dose of clopidogrel prior to a diagnostic coronary angiography in the past. The symptoms improved dramatically on discontinuation of clopidogrel. There was no recurrence of symptoms with prasugrel. This describes possibly the second incidence of recurrent arthritis with clopidogrel therapy.
Self-Reported Preconception Care of HIV-Positive Women of Reproductive Potential
Authors: Loutfy Mona R. , Blitz Sandra , Zhang Yimeng , Hart Trevor A. , Walmsley Sharon L. , Smaill Fiona M. , Rachlis Anita R. , Yudin Mark H. , Angel Jonathan B. , Ralph Edward D. , Tharao Wangari , Raboud Janet M. ,   for the Ontario HIV Fertility Research Team
Published: August 2013

Objectives:

We determined the proportion and correlates of self-reported pregnancy planning discussions (that is preconception counseling) that HIV-positive women reported to their family physicians (FPs), HIV specialists, and obstetrician/gynecologists (OB/Gyns).

Methods:

In a cross-sectional substudy, HIV-positive women of reproductive potential were asked whether their care providers discussed pregnancy planning. Logistic regression was used to calculate odds ratios for the correlates of preconception counseling.

Results:

A total of 431 eligible participants (median age 38, interquartile range = 32-43) reported having discussion with a physician (92% FP, 96% HIV specialists, and 45% OB/Gyns). In all, 34%, 41%, and 38% had their pregnancy planning discussion with FP, HIV specialist, and Ob/Gyns, respectively; 51% overall. In the multivariable model, significant correlates of preconception counseling were age ( P = .02), marital status ( P < .01), number of years living in Canada ( P < .001), and age of youngest child ( P < .01).

Conclusions:

Preconception care in our cohort was suboptimal. We recommend that counseling on healthy preconception should be part of routine HIV care.
Horizontally transferred genes in the genome of Pacific white shrimp, Litopenaeus vannamei
Authors: Yuan Jian-Bo , Zhang Xiao-Jun , Liu Cheng-Zhang , Wei Jian-Kai , Li Fu-Hua , Xiang Jian-Hai
Published: August 2013

Background

In recent years, as the development of next-generation sequencing technology, a growing number of genes have been reported as being horizontally transferred from prokaryotes to eukaryotes, most of them involving arthropods. As a member of the phylum Arthropoda, the Pacific white shrimpLitopenaeus vannameihas to adapt to the complex water environments with various symbiotic or parasitic microorganisms, which provide a platform for horizontal gene transfer (HGT).

Results

In this study, we analyzed the genome-wide HGT events inL. vannamei. Through homology search and phylogenetic analysis, followed by experimental PCR confirmation, 14 genes with HGT event were identified: 12 of them were transferred from bacteria and two from fungi. Structure analysis of these genes showed that the introns of the two fungi-originated genes were substituted by shrimp DNA fragment, two genes transferred from bacteria had shrimp specific introns inserted in them. Furthermore, around other three bacteria-originated genes, there were three large DNA segments inserted into the shrimp genome. One segment was a transposon that fully transferred, and the other two segments contained only coding regions of bacteria. Functional prediction of these 14 genes showed that 6 of them might be related to energy metabolism, and 4 others related to defense of the organism.

Conclusions

HGT events from bacteria or fungi were happened in the genome ofL. vannamei, and these horizontally transferred genes can be transcribed in shrimp. This is the first time to report the existence of horizontally transferred genes in shrimp. Importantly, most of these genes are exposed to a negative selection pressure and appeared to be functional.
Evidence for inflammation-mediated memory dysfunction in gastropods: putative PLA2and COX inhibitors abolish long-term memory failure induced by systemic immune challenges
Authors: Hermann Petra M , Park Deborah , Beaulieu Emily , Wildering Willem C
Published: August 2013

Background

Previous studies associate lipid peroxidation with long-term memory (LTM) failure in a gastropod model (Lymnaea stagnalis) of associative learning and memory. This process involves activation of Phospholipase A2 (PLA2), an enzyme mediating the release of fatty acids such as arachidonic acid that form the precursor for a variety of pro-inflammatory lipid metabolites. This study investigated the effect of biologically realistic challenges of L. stagnalis host defense response system on LTM function and potential involvement of PLA2, COX and LOX therein.

Results

Systemic immune challenges by means of β-glucan laminarin injections induced elevated H2O2 release from L. stagnalis circulatory immune cells within 3 hrs of treatment. This effect dissipated within 24 hrs after treatment. Laminarin exposure has no direct effect on neuronal activity. Laminarin injections disrupted LTM formation if training followed within 1 hr after injection but had no behavioural impact if training started 24 hrs after treatment. Intermediate term memory was not affected by laminarin injection. Chemosensory and motor functions underpinning the feeding response involved in this learning model were not affected by laminarin injection. Laminarin’s suppression of LTM induction was reversed by treatment with aristolochic acid, a PLA2 inhibitor, or indomethacin, a putative COX inhibitor, but not by treatment with nordihydro-guaiaretic acid, a putative LOX inhibitor.

Conclusions

A systemic immune challenge administered shortly before behavioural training impairs associative LTM function in our model that can be countered with putative inhibitors of PLA2 and COX, but not LOX. As such, this study establishes a mechanistic link between the state of activity of this gastropod’s innate immune system and higher order nervous system function. Our findings underwrite the rapidly expanding view of neuroinflammatory processes as a fundamental, evolutionary conserved cause of cognitive and other nervous system disorders.
Assessing the bioconfinement potential of a Nicotianahybrid platform for use in plant molecular farming applications
Authors: Rice J Hollis , Mundell Richard E , Millwood Reginald J , Chambers Orlando D , Stewart C Neal , Davies H Maelor
Published: August 2013

Background

The introduction of pharmaceutical traits in tobacco for commercial production could benefit from the utilization of a transgene bioconfinement system. It has been observed that interspecific F1
Nicotiana hybrids (Nicotiana tabacum × Nicotiana glauca) are sterile and thus proposed that hybrids could be suitable bioconfined hosts for biomanufacturing. We genetically tagged hybrids with green fluorescent protein (GFP), which was used as a visual marker to enable gene flow tracking and quantification for field and greenhouse studies. GFP was used as a useful proxy for pharmaceutical transgenes.

Results

Analysis of DNA content revealed significant genomic downsizing of the hybrid relative to that of N. tabacum. Hybrid pollen was capable of germination in vitro, albeit with a very low frequency and with significant differences between plants. In two field experiments, one each in Tennessee and Kentucky, we detected outcrossing at only one location (Tennessee) at 1.4%. Additionally, from 50 hybrid plants at each field site, formation of 84 and 16 seed was observed, respectively. Similar conclusions about hybrid fertility were drawn from greenhouse crosses. In terms of above-ground biomass, the hybrid yield was not significantly different than that of N. tabacum in the field.

Conclusion

N. tabacum × N. glauca hybrids show potential to contribute to a bioconfinement- and biomanufacturing host system. Hybrids exhibit extremely low fertility with no difference of green biomass yields relative to N. tabacum. In addition, hybrids are morphologically distinguishable from tobacco allowing for identity preservation. This hybrid system for biomanufacturing would optimally be used where N. glauca is not present and in physical isolation of N. tabacum production to provide total bioconfinement.
Bacterial isolates and drug susceptibility patterns of ear discharge from patients with ear infection at Gondar University Hospital, Northwest Ethiopia
Authors: Muluye Dagnachew , Wondimeneh Yitayih , Ferede Getachew , Moges Feleke , Nega Tesfaye
Published: August 2013

Background

Ear infection is a common problem for both children and adults especially in developing countries. However in Ethiopia particularly in the study area, there is no recent data that shows the magnitude of the problem. The aim of this study was to determine the bacterial isolates and their drug susceptibility patterns from patients who had ear infection.

Method

A retrospective study was conducted from September, 2009 to August, 2012 at Gondar University Hospital, Northwest Ethiopia. Ear discharge samples were cultured on MacConkey agar, blood agar and chocolate agar plates. A standard biochemical procedure was used for full identification of bacterial isolates. Antimicrobial susceptibility tests were done on Mueller-Hinton agar by using disk diffusion method. Data were entered and analyzed by using SPSS version 20 software and P-value of < 0.05 was considered statistically significant.

Result

A total of 228 ear discharge samples were tested for bacterial isolation and 204 (89.5%) cases were found to have bacterial isolates. From the total bacterial isolates, 115 (56.4%) were gram negative bacteria and the predominant isolate was proteus species (27.5%). Of individuals who had ear infection, 185 (90.7%) had single bacterial infection while 19 (9.3%) had mixed infections. Under five children were more affected by ear infection. The prevalence of ear infection was significantly high in males (63.7 vs 36.3%) (P = 0.017). Of all bacterial isolates, 192 (94.1%) had multiple antibiotic resistant pattern. Non Lactose Fermenter Gram Negative Rods (46.0%), Klebsella species (47.7%) and Pseudomonas species (48.5%) were resistant against the commonly used antibiotics.

Conclusion

The prevalence of ear infection was very high in the study area. Majority of the bacterial isolates were resistant to multiple antibiotics. Hence antibiotics susceptibility test is mandatory before prescribing any antibiotics.
Qingfei Xiaoyan Wan alleviates asthma through multi-target network regulation
Authors: Zhao Zhenying , Miao Yingbo , Pan Pengwei , Cheng Binfeng , Bai Gang , Wu Hong
Published: August 2013

Background

Qingfei Xiaoyan Wan (QFXY), a traditional Chinese formula, is widely used for relieving cough, asthma, upper respiratory tract infection, bronchitis, pneumonia, and etc. in clinic. Comparing with other anti-asthma drugs, it is characterised with moderate and persistent efficacy as well as few side effects, however, the underlying action mechanism still remains elusive. This study aimed to identify QFXY multi-target network regulation as an asthma controller.

Methods

This study established asthma model induced by histamine phosphate and acetylcholine chloride (His&Ach) in guinea pigs, which then were administered orally with QFXY. Hematoxylin-Eosin staining sections were applied for evaluating QFXY effect. In both Model and QFXY groups, customized microarrays and 2D electrophoresis were adopted to detect differentially expressed genes (diff genes) and proteins (diff proteins) respectively, and some diff proteins were identified with MALDI-TOF/MS. The checked diff genes and proteins underwent Cluster, GO and KEGG analysis. Based on GAD and HPRD databases, QFXY-asthma target regulation network was constructed.

Results

His&Ach-induced asthma model of guinea pigs was established. HE sections presented anti-inflammation and anti-remodelling effects of QFXY. Comparing with the Model group, 55 diff genes and 6 diff proteins were identified in QFXY group. Validation by qPCR and Western blot showed the microarray and 2D data reliable. Furthermore, QFXY-asthma target regulation network was achieved.

Conclusions

A primarily combined genomic and proteomic screening of QFXY targets displayed a series of candidate genes and proteins, which indicated that the effect of QFXY relied on the combined mechanism, anti-inflammation and anti-remodelling, as well as influencing signal transduction in vivo.
Shikonin suppresses ERK 1/2 phosphorylation during the early stages of adipocyte differentiation in 3T3-L1 cells
Authors: Gwon So Young , Ahn Ji Yun , Jung Chang Hwa , Moon Bo Kyung , Ha Tae Youl
Published: August 2013

Background

The naphthoquinone pigment, shikonin, is a major component of Lithospermum erythrorhizon and has been shown to have various biological functions, including antimicrobial, anti-inflammatory, and antitumor effects. In this study, we investigated the effect of shikonin on adipocyte differentiation and its mechanism of action in 3T3-L1 cells.

Methods

To investigate the effects of shikonin on adipocyte differentiation, 3T3-L1 cells were induced to differentiate using 3-isobutyl-1-methylzanthine, dexamethasone, and insulin (MDI) for 8 days in the presence of 0–2 μM shikonin. Oil Red O staining was performed to determine the lipid accumulation in 3T3-L1 cells. To elucidate the anti-adipogenic mechanism of shikonin, adipogenic transcription factors, the phosphorylation levels of ERK, and adipogenic gene expression were analyzed by Western blotting and quantitative real-time PCR. To further confirm that shikonin inhibits adipogenic differentiation through downregulation of ERK 1/2 activity, 3T3-L1 cells were treated with shikonin in the presence of FGF-2, an activator, or PD98059, an inhibitor, of the ERK1/2 signaling pathway.

Results

Shikonin effectively suppressed adipogenesis and downregulated the protein levels of 2 major transcription factors, PPARγ and C/EBPα, as well as the adipocyte specific gene aP2 in a dose-dependent manner. qRT-PCR analysis revealed that shikonin inhibited mRNA expression of adipogenesis-related genes, such as PPARγ, C/EBPα, and aP2. Adipocyte differentiation was mediated by ERK 1/2 phosphorylation, which was confirmed by pretreatment with PD98059 (an ERK 1/2 inhibitor) or FGF-2 (an ERK 1/2 activator). The phosphorylation of ERK1/2 during the early stages of adipogenesis in 3T3-L1 cells was inhibited by shikonin. We also confirmed that FGF-2-stimulated ERK 1/2 activity was attenuated by shikonin.

Conclusions

These results demonstrate that shikonin inhibits adipogenic differentiation via suppression of the ERK signaling pathway during the early stages of adipogenesis.
Microsatellite genotyping of Plasmodium vivax infections and their relapses in pregnant and non-pregnant patients on the Thai-Myanmar border
Authors: Thanapongpichat Supinya , McGready Rose , Luxemburger Christine , Day Nicholas PJ , White Nicholas J , Nosten Francois , Snounou Georges , Imwong Mallika
Published: August 2013

Background

Plasmodium vivax infections in pregnancy are associated with low birth weight and anaemia. This parasites species is also characterised by relapses, erythrocytic infections initiated by the activation of the dormant liver stages, the hypnozoites, to mature. Genotyping of P. vivax using microsatellite markers has opened the way to comparative investigations of parasite populations. The aim of the study was to assess whether there were any differences between the parasites found in pregnant and non-pregnant patients, and/or between the admission infections and recurrent episodes during follow-up.

Methods

Blood samples were collected from 18 pregnant and 18 non-pregnant patients, who had at least two recurrent episodes during follow-up, that were recruited in two previous trials on the efficacy of chloroquine treatment of P. vivax infections on the Thai-Myanmar border. DNA was purified and the P. vivax populations genotyped with respect to eight polymorphic microsatellite markers. Analyses of the genetic diversity, multiplicity of infection (MOI), and a comparison of the genotypes in the samples from each patient were conducted.

Results

The P. vivax parasites present in the samples exhibited high genetic diversity (6 to 15 distinct allelic variants found for the 8 loci). Similar expected heterozygosity (H
e) values were obtained for isolates from pregnant (0.837) and non-pregnant patients (0.852). There were modest differences between the MOI values calculated for both admission and recurrence samples from the pregnant patients (2.00 and 2.05, respectively) and the equivalent samples from the non-pregnant patients (1.67 and 1.64, respectively). Furthermore, the mean number of distinct alleles enumerated in the admission samples from the pregnant (6.88) and non-pregnant (7.63) patients were significantly lower than that found in the corresponding recurrent episodes samples (9.25 and 9.63, respectively).

Conclusions

The P. vivax populations circulating in inhabitants along the Thai-Myanmar border, an area of low malaria transmission, displayed high genetic diversity. A subtle increase in the multiplicity of P. vivax infections in pregnant patients suggests a higher susceptibility to infection. The higher allelic diversity in the relapse as compared to the admission samples in both patient groups is consistent with the hypothesis that a febrile episode promotes the activation of hypnozoites.
Krüppel-like factor 4 regulates genetic stability in mouse embryonic fibroblasts
Authors: El-Karim Enas A , Hagos Engda G , Ghaleb Amr M , Yu Bing , Yang Vincent W
Published: August 2013

Background

Krüppel-like factor 4 (KLF4) is a member of the KLF family of transcription factors and regulates proliferation, differentiation, apoptosis and somatic cell reprogramming. Evidence also suggests that KLF4 is a tumor suppressor in certain cancers including colorectal cancer. We previously showed that KLF4 inhibits cell cycle progression following DNA damage and that mouse embryonic fibroblasts (MEFs) null for Klf4 are genetically unstable, as evidenced by increased rates of cell proliferation, and the presence of DNA double strand breaks (DSBs), centrosome amplification, chromosome aberrations and aneuploidy.

Methods

To determine whether re-expression of Klf4 corrects the observed genetic instability in MEFs null for Klf4 (Klf4

−/−
), we transfected Klf4

−/−
MEFs with Klf4-expressing plasmids and compared the results to wild type (Klf4

+/+
) and untransfected or mock-transfected Klf4

−/−
MEFs.

Results

We show that overexpression of Klf4 in Klf4

−/−
MEFs reduced cell proliferation rates and the proportion of cells with DSBs, abnormal centrosome numbers, aneuploidy and micronuclei. In addition, Klf4-transfected Klf4

−/−
MEFs exhibited a more robust DNA damage repair response as demonstrated by the greater rate in disappearance of γ-H2AX and 53BP1 foci following γ-irradiation.

Conclusion

Taken together these findings provide evidence that KLF4 plays a crucial role in the maintenance of genetic stability by modulating the DNA damage response and repair processes.
Association between APOE, SCARB1, PPARα polymorphisms and serum lipids in a population of Lithuanian adults
Authors: Smalinskiene Alina , Petkeviciene Janina , Luksiene Dalia , Jureniene Kristina , Klumbiene Jurate , Lesauskaite Vaiva
Published: August 2013

Background

Dyslipidemia is one of several known risk factors for coronary heart disease, a leading cause of death in Lithuania. Blood lipid levels are influenced by multiple genetic and environmental factors. Epidemiological studies demonstrated the impact of nutrition on lipid levels within the Lithuanian population although the role of genetic factors for dyslipidemias has not yet been studied. The objective of this study was to assess the distribution of the APOE, SCARB1, PPARα genotypes in the Lithuanian adult population and to determine the relationship of these genotypes with dyslipidemia.

Methods

A cross-sectional health survey was carried out in a representative random sample of the Lithuanian population aged 25–64 (n=1030). A variety of single-nucleotide polymorphisms (SNPs) of the APOE (rs429358 and rs7412), SCARB1 (rs5888) and PPARα (rs1800206) genes were assessed using real-time polymerase chain reaction. Serum lipids were determined using enzymatic methods.

Results/Principal findings

Men and women with the APOE2 genotype had the lowest level of total and low-density lipoprotein cholesterol (LDL-C). Men with the APOE2 genotype had significantly higher levels of triglycerides (TG) than those with the APOE3 genotype. In men, the carriers of the APOE4 genotype had higher odds ratios (OR) of reduced (<1.0 mmol/L) high density lipoprotein cholesterol (HDL-C) levels versus APOE3 carriers (OR=1.98; 95% CI=1.05-3.74). The odds of having elevated (>1.7 mmol/L) TG levels was significantly lower in SCARB1 genotype CT carriers compared to men with the SCARB1 genotype CC (OR=0.50; 95% CI=0.31-0.79). In men, carriers of the PPARα genotype CG had higher OR of elevated TG levels versus carriers of PPARα genotype CC (OR=2.67; 95% CI=1.15-6.16). The odds of having high LDL-C levels were lower in women with the APOE2 genotype as compared to APOE3 genotype carriers (OR=0.35; 95% CI=0.22-0.57).

Conclusions/Significance

Our data suggest a gender difference in the associations between APOE, SCARB1, PPARα genotypes and lipid levels. In men, the APOE4 genotype and PPARα genotype CG were correlated with an atherogenic lipid profile while the SCARB1 genotype CT had an atheroprotective effect. In women, APOE2 carriers had the lowest odds of high LDL-C.
A case report of de novo hepatocellular carcinoma after living donor liver transplantation
Authors: Yu Songfeng , Guo Hua , Zhuang Li , Yu Jun , Yan Sheng , Zhang Min , Wang Weilin , Zheng Shusen
Published: August 2013

Post-transplant malignancy is the major cause of later death of recipients after liver transplantation. Tumor recurrence after liver transplantation for patients with hepatocellular carcinoma in the end stage of cirrhosis has been frequently encountered. However, de novo hepatocellular carcinoma originating from the liver allograft has only rarely been reported. Here we reported a case of de novo hepatocellular carcinoma developed 2 years after living donor liver transplantation for hepatitis B-related liver cirrhosis with viral YMDD mutation. To the best of our knowledge, this is the first report of de novo hepatocellular carcinoma in a liver graft with recurrent hepatitis B virus infection after liver transplantation for hepatitis B-related liver cirrhosis with YMDD mutation. Moreover, the de novo cancer first presented as a lung mass with minimal liver involvement and was obscured by a pulmonary fungal infection.
Inferior vena cava tumor thrombus that directly infiltrated from paracaval lymph node metastases in a patient with recurrent hepatocellular carcinoma
Authors: Imada Shinya , Ishiyama Kohei , Ide Kentaro , Kobayashi Tsuyoshi , Amano Hironobu , Tashiro Hirotaka , Arihiro Koji , Aikata Hiroshi , Chayama Kazuaki , Ohdan Hideki
Published: August 2013

Herein, we present the case of a patient with recurrent hepatocellular carcinoma (HCC) who had paracaval lymph node (LN) metastases with an inferior vena cava (IVC) tumor thrombus after a hepatectomy. A 65-year-old man with chronic hepatitis B virus infection received an extended anterior segmentectomy because of two hepatic tumors, located in segments 7 and 8. Histological examination of both resected specimens showed mostly moderately differentiated HCC with some poorly differentiated areas, and liver cirrhosis (A2/F4). Because the patient had an elevated α-fetoprotein serum level, abdominal computed tomography (CT) was performed. Abdominal CT revealed a 9-mm-diameter recurrent tumor in hepatic segment 3 and paracaval LN metastases with an IVC tumor thrombus at 8 months after the first operation. The patient received transcatheter arterial chemoembolization as treatment for the intrahepatic recurrence, following resection of the paracaval LN metastases and removal of the IVC tumor thrombus. In this case, the paracaval LN metastases had directly infiltrated the IVC via the lumbar veins, resulting in an IVC tumor thrombus, which usually develops from an intrahepatic tumor via the hepatic vein. The development of an IVC tumor thrombus with HCC recurrence, as in this case, is very rare, and based on a PubMed search, we believe this report may be the first to describe this condition.
A variable step-size strategy for distributed estimation over adaptive networks
Authors: Bin Saeed Muhammad O , Zerguine Azzedine , Zummo Salam A
Published: August 2013

A lot of work has been done recently to develop algorithms that utilize the distributed structure of anad hocwireless sensor network to estimate a certain parameter of interest. One such algorithm is called diffusion least-mean squares (DLMS). This algorithm estimates the parameter of interest using the cooperation between neighboring sensors within the network. The present work proposes an improvement on the DLMS algorithm by using a variable step-size LMS (VSSLMS) algorithm. In this work, first, the well-known variants of VSSLMS algorithms are compared with each other in order to select the most suitable algorithm which provides the best trade-off between performance and complexity. Second, the detailed convergence and steady-state analyses of the selected VSSLMS algorithm are performed. Finally, extensive simulations are carried out to test the robustness of the proposed algorithm under different scenarios. Moreover, the simulation results are found to corroborate the theoretical findings very well.
Establishment of cell lines with increased susceptibility to EV71/CA16 by stable overexpression of SCARB2
Authors: Li Xiaojun , Fan Peihu , Jin Jun , Su Weiheng , An Dong , Xu Lin , Sun Shiyang , Zhang Yan , Meng Xiangyu , Gao Feng , Kong Wei , Jiang Chunlai
Published: August 2013

Background

Human enterovirus type 71 (EV71) and Coxsackievirus A group type 16 (CA16) belong to human Enterovirus species A of the family Picornaviridae. These viruses are recognized as the major pathogens responsible for epidemics of hand-foot-mouth disease (HFMD), which presents with fever and vesicular eruptions of palms, soles of the feet or mouth. Human scavenger receptor class B, member 2 (SCARB2) has been identified as the receptor for both EV71 and CA16, as overexpression of SCARB2 in cells can enhance virus replication significantly.

Methods

In this study, we used a lentivirus packaging vector to transduce the SCARB2 gene into human embryonic kidney cells (293), human rhabdomyosarcoma cells (RD) and African green monkey kidney cells (Vero) to create stable expression lines. Expression of SCARB2 in the resulting three transgenic cell lines was confirmed by real-time RT-PCR, immunofluorescence and flow cytometry.

Results

Levels of SCARB2 mRNA determined by real-time RT-PCR in 293-SCARB2 (293S) or RD-SCARB2 (RDS) transgenic cell lines were approximately 2 × 102 times higher than those in 293 and RD cells, respectively, and three times higher in Vero-SCARB2 (VeroS) than in Vero cells. Furthermore, EV71 and CA16 virus titers in 293S and RDS cells were 102–103-fold higher (detected in RD cell) than those in the parental cells, and a 10-fold higher titer of EV71 was achieved in VeroS cells compared with that in Vero cells.

Conclusions

We established for the first time three cell lines stably overexpressing SCARB2, which showed drastic increases in susceptibility to EV71/CA16 infection. These optimal cell lines may be utilized to develop inactivated vaccines for EV71/CA16 and facilitate rapid detection and isolation of HFMD pathogens or other Enterovirus serotypes. Furthermore, these stable cell lines also can serve as tools to facilitate drug screenings as well as molecular studies on virus-host interactions and pathogenesis of causative agents for HFMD.
Degradation of aqueous synthesized CdTe/ZnS quantum dots in mice: differential blood kinetics and biodistribution of cadmium and tellurium
Authors: Liu Na , Mu Ying , Chen Yi , Sun Hubo , Han Sihai , Wang Mengmeng , Wang Hui , Li Yanbo , Xu Qian , Huang Peili , Sun Zhiwei
Published: August 2013

Background

Quantum dots (QDs) have been used as novel fluorescent nanoprobes for various bioapplications. The degradation of QDs, and consequent release of free cadmium ions, have been suggested to be the causes of their overall toxicity. However, in contrast to sufficient investigations regarding the biological fate of QDs, a paucity of studies have reported their chemical fate in vivo. Therefore, the overall aim of our study was to understand the chemical fate of QDs in vivo and explore analytical techniques or methods that could be used to define the chemical fate of QDs in vivo.

Methods

Male ICR mice were administered a single intravenous dose (0.2 μmol/kg) of aqueous synthesized CdTe/ZnS aqQDs. Inductively coupled plasma-mass spectrometry (ICP-MS) was used to simultaneously measure the concentrations of cadmium (Cd) and tellurium (Te) in the blood and tissues over the course of a 28 day period. We compared the blood kinetic parameters and biodistributions of Cd and Te, and used the molar ratio of Cd:Te as a marker for QDs degradation.

Results

Cd and Te display different blood kinetics and biodistribution profiles. The Cd:Te ratio in the blood did not vary significantly within the first hour compared with intact CdTe/ZnS aqQDs. The Cd:Te ratio decreased gradually over time from the 6 h time point on. Cd accumulated in the liver, kidneys, and spleen. Te was distributed primarily to the kidneys. Sharp time-dependent increases in the Cd:Te ratio were found in liver tissues.

Conclusions

QDs can undergo degradation in vivo. In vitro, QDs are chemically stable and do not elicit the same biological responses or consequences as they do in vivo. Our methods might provide valuable information regarding the degradation of QDs in vivo and may enable the design and development of QDs for biological and biomedical applications.
Treading & threading memories: a personal encounter with forest and people in Southern Venezuela
Authors: Zent Egleé L
Published: August 2013

This brief essay, which represents the third editorial of the series "Recollections, Reflections, and Revelations: Ethnobiologists and their First Time in the Field", captures a few memories of the author's first fieldwork in the Venezuelan rainforest. It is a collage of objects, subjects, feelings, spaces, and events that pendulate in spheres of meaning straddling between the author's identities as both a student and a woman. The author's evocations of fifteen years ago are diluted in lasting reflections about what could be ethnoecology embraced by spaces of interactions and associations between organisms and their surroundings.