1,890 research outputs found

    Genotoxicity evaluation of the insecticide ethion in root of Allium cepa L.

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    In this study, the genotoxic effects of ethion were investigated in the mitotic cell division of Allium cepa. Primary roots of A. cepa were treated with various concentrations (25, 50, 75, and 100%) of ethion solutions for different duration of time. The result revealed that increase in the concentration and duration of treatment decreases the mitotic indices. 24 h treatment at 100% concentration of ethion induced lowest mitotic index (20.08%) than that of the control (36.37%). The percentage of chromosomal abnormalities in different mitotic stages was significantly generally higher than that of the control in all the treatment period and concentrations. These abnormalities appeared in various degrees depending on the treatment duration and concentrations of ethion. The abnormalities in dividing cell reached a maximum value of 11.30% after 12 h of treatment at 75% concentration. The type of abnormalitiesproduced were scattered prophase, non-synchronized condensation of chromosome, disturbed prophase, equatorial plate shifting, sticky chromosomes, C-metaphase and sticky metaphase. Overall, it can be concluded that ethion has a potential genotoxic effects on mitotic divisions in A. cepa root tip cells. So, it will be necessary to test the mutagenic potential of ethion on a more intensive and extensive basis especially on non-target systems before it is recommended for wider use in agriculturalfield

    The Hydration Structure at Yttria-Stabilized Cubic Zirconia (110)-Water Interface with Sub-Angstrom Resolution

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    The interfacial hydration structure of yttria-stabilized cubic zirconia (110) surface in contact with water was determined with ~0.5 Å resolution by high-resolution X-ray reflectivity measurement. The terminal layer shows a reduced electron density compared to the following substrate lattice layers, which indicates there are additional defects generated by metal depletion as well as intrinsic oxygen vacancies, both of which are apparently filled by water species. Above this top surface layer, two additional adsorbed layers are observed forming a characteristic interfacial hydration structure. The first adsorbed layer shows abnormally high density as pure water and likely includes metal species, whereas the second layer consists of pure water. The observed interfacial hydration structure seems responsible for local equilibration of the defective surface in water and eventually regulating the long-term degradation processes. The multitude of water interactions with the zirconia surface results in the complex but highly ordered interfacial structure constituting the reaction front.ope

    Age groups and spread of influenza: implications for vaccination strategy

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    <p>Abstract</p> <p>Background</p> <p>The unpredictable nature of the potentially devastating impact of 2009 pH1N1 influenza pandemic highlights the need for pandemic preparedness planning, where modeling studies could be most useful for simulations of possible future scenarios.</p> <p>Methods</p> <p>A compartmental model with pre-symptomatic and asymptomatic influenza infections is proposed which incorporates age groups as well as intervention measures such as age-specific vaccination, in order to study spread of influenza in a community.</p> <p>Results</p> <p>We derive the basic reproduction number and other effective reproduction numbers under various intervention measures. For illustration, we make use of the Pneumonia and Influenza (P&I) mortality data and vaccination data of the very young (age 0-2) and the very old (age >64) during 2004-2005 Taiwan winter influenza season to fit our model and to compute the relevant reproduction numbers. The reproduction number for this winter flu season is estimated to be slightly above one (~1.0001).</p> <p>Conclusions</p> <p>Comparatively large errors in fitting the P&I mortality data of the elderly (>64) were observed shortly after winter school closings in January, which may indicate the impact of younger, more active age groups transmitting influenza to other age groups outside of the school settings; in particular, to the elderly in the households. Pre-symptomatic infections seemed to have little effect on the model fit, while asymptomatic infection by asymptomatic infectives has a more pronounced impact on the model fit for the elderly mortality, perhaps indicating a larger role in disease transmission by asymptomatic infection. Simulations indicate that the impact of vaccination on the disease incidence might not be fully revealed in the change (or the lack thereof) in the effective reproduction number with interventions, but could still be substantial. The estimated per contact transmission probability for susceptible elderly is significantly higher than that of any other age group, perhaps highlighting the vulnerability of the elderly due to close contacts with their caretakers from other age groups. The relative impact of targeting the very young and the very old for vaccination was weakened by their relative inactivity, thus giving evidence of the lack of impact of vaccinating these two groups on the overall transmissibility of the disease in the community. This further underscores the need for morbidity-based strategy to prevent elderly mortality.</p

    A transient homotypic interaction model for the influenza A virus NS1 protein effector domain

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    Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal 'tail'. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed 'helix-closed' and 'helix-open') in virus-infected cells. 'Helix-closed' conformations appear to enhance dsRNA binding, and 'helix-open' conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins

    Systems biology approaches applied to regenerative medicine

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    Systems biology is the creation of theoretical and mathematical models for the study of biological systems, as an engine for hypothesis generation and to provide context to experimental data. It is underpinned by the collection and analysis of complex datasets from different biological systems, including global gene, RNA, protein and metabolite profiles. Regenerative medicine seeks to replace or repair tissues with compromised function (for example, through injury, deficiency or pathology), in order to improve their functionality. In this paper, we will address the application of systems biology approaches to the study of regenerative medicine, with a particular focus on approaches to study modifications to the genome, transcripts and small RNAs, proteins and metabolites

    Does a small central Nd:YAG posterior capsulotomy improve peripheral fundal visualisation for the Vitreoretinal surgeon?

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    BACKGROUND: To evaluate the effect of Nd:YAG capsulotomy for posterior capsular opacification (PCO) on visualisation of the peripheral fundus with scleral indentation. METHODS: Patients undergoing Nd:YAG capsulotomy for PCO were examined pre- and four weeks post- Nd:YAG capsulotomy. In order to give a quantitative measure of visualisation of the peripheral retina, a novel scalar measurement was developed. Changes in the degree of visualisation following Nd:YAG capsulotomy were calculated. RESULTS: There was a significant improvement in fundal visualisation of the retinal periphery with scleral indentation following Nd:YAG capsulotomy (p = 0.001). CONCLUSION: Peripheral fundal visualisation with scleral indentation improves following a small central Nd:YAG capsulotomy. This finding is important in relation to the detection of peripheral pseudophakic retinal breaks, particularly in those patients deemed at high risk following Nd:YAG capsulotomy

    RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord

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    ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned \u3e50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of differentially expressed genes (DEG’s). Ingenuity Pathways Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF) found to be a major pathway regulator (IPA) and TNFα-induced protein 2 (TNFAIP2) as a major network “hub” gene (WGCNA). Using the oPOSSUM algorithm, we analyzed transcription factors (TF) controlling expression of the nine DEG/hub genes in the ALS samples and identified TF’s involved in inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms) reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be helpful in ALS patients

    Tetramethylpyrazine attenuates spinal cord ischemic injury due to aortic cross-clamping in rabbits

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    BACKGROUND: Lower limb paralysis occurs in 11% of patients after surgical procedure of thoracic or thoracoabdominal aneurysms and is an unpredictable and distressful complication. The aim of this study was to investigate the effects of tetramethylpyrazine (TMP), an intravenous drug made from traditional Chinese herbs, on the neurologic outcome and hisotpathology after transient spinal cord ischemia in rabbits. METHODS: Forty-five male New Zealand white rabbits were anesthetized with isoflurane and spinal cord ischemia was induced for 20 min by infrarenal aortic occlusion. Animals were randomly allocated to one of five groups (n = 8 each). Group C received no pharmacologic intervention. Group P received intravenous infusion of 30 mg·kg(-1) TMP within 30 min before aortic occlusion. Group T(1), Group T(2) and Group T(3) received intravenous infusion of 15, 30 and 60 mg·kg(-1) TMP respectively within 30 min after reperfusion. In the sham group (n = 5), the animals underwent the same procedures as the control group except infrarental aortic unocclusion. Neurologic status was scored by using the Tarlov criteria (in which 4 is normal and 0 is paraplegia) at 4 h, 8 h, 12 h, 24 h, and 48 h after reperfusion. All animals were sacrificed at 48 h after reperfusion and the spinal cords (L(5)) were removed immediately for histopathologic study. RESULTS: All animals in the control group became paraplegic. Neurologic status and histopathology (48 h) in the Groups P, T(2) and T(3) were significantly better than those in the control group (P < 0.05). There was a strong correlation between the final neurologic scores and the number of normal neurons in the anterior spinal cord (r = 0.776, P < 0.01). CONCLUSION: Tetramethylpyrazine significantly reduces neurologic injury related to spinal cord ischemia and reperfusion after aortic occlusion within a certain range of dose
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