Lethality Index 2008-2014: Less shootings, same lethality, more opacity

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Carlos Silva Forné

2017-11-01

Full Text Available This article evaluates the use of lethal force by Mexican federal security forces during shootings with presumed members of organized crime from 2008-2014. The authors use official data and press reports on deaths and wounded in shootings to construct indicators such as the number of dead civilians over the number of dead officials from the federal security forces and the number of dead civilians over the number of wounded civilians. In a context where certain factors that contribute to an excessive use of force become more common, the results of the study show a growing use of lethal force. This raises questions over the possible excessive use of lethal force as a normal or systematic practice. The study also shows a growing context of opacity in the information available to evaluate the use of lethal force and the general lack of a legal framework to regulate the use of lethal force in Mexico.

Relationship between chromosomal aberration of germ cells and dominant lethal mutation in male mice after low dosage of X-irradiation

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Mingdong, Wang; Baochen, Yang; Yuke, Jin [Bethune (N.) Medical Univ., Changchun, JL (China). Dept. of Gentics

1989-01-01

The relationship between chromosomal aberration adn dominant mutation in spermatocytes of late pachytene phase in male mice after a single X-irridiation was reported. It was found that the frequency of aberrant cells was correlative to the rate of fetal death, the latter was being about 2.5 times as high as the former. The frequency of dominant lethal mutation induced by X-irradiation is 2.1995x10{sup -3} gamete {center dot} 10 mGy.

Histopathological effects of lethal and sub-lethal concentrations of ...

African Journals Online (AJOL)

The histopathological effects of lethal and sub-lethal concentrations of glyphosate on African catfish Clarias gariepinus were investigated. C. gariepinus juveniles were assessed in a static renewal bioassay for 96 hours (acute toxicity) and 28 days (chronic toxicity) using varying concentrations (0.0 mg/l 20.0 mg/l, 30.0 mg/l, ...

Lethal and sublethal effects of pesticides in the management of Polyphagotarsonemus latus (Banks) (Acari: Tarsonemidae) on Capsicum annuum L.

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Breda, Mariana O; Oliveira, José V; Esteves Filho, Alberto B; Barbosa, Douglas Rs; Santos, Andrezo A

2017-10-01

The evaluation of lethal and sublethal effects is of great importance for a complete assessment of the total impact of chemical compounds upon pest populations and the development of management strategies. In this study, we evaluated the lethal and sublethal effects of different synthetic and botanical products on the broad mite Polyphagotarsonemus latus (Banks), a major pest of Capsicum annuum L. and other crops. Abamectin had the highest lethal effect on P. latus, followed by spiromesifen, azadirachtin, neem oil and nitrogen fertiliser + citric acid. The sublethal effects of the products were indicated by the influence on mite population growth, affecting the numbers of females, males, larvae, pupae and eggs. Furthermore, a negative instantaneous rate of increase in P. latus and repellent effects were observed. The lethal and sublethal effects of abamectin, spiromesifen, azadirachtin and neem oil significantly affect P. latus population growth, as well as causing repellence to this mite on C. annuum, and they should be considered in the integrated pest management of this mite. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Semi-lethal high temperature and heat tolerance of eight Camellia species

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He, XY; Ye, H; Ma, JL; Zhang, RQ; Chen, GC; Xia, YY

2012-01-01

Annual leaf segments of eight Camellia species were used to study the heat tolerance by an electrical conductivity method, in combination with a Logistic equation to ascertain the semi-lethal high temperature by fitting the cell injury rate curve. Te relationship between the processing temperature and the cell injury rate in Camellia showed a typical "S" shaped curve, following the Logistic model. Te correlation coeficient was above 0.95. Te semi-lethal high temperature LT50 of the eight Came...

Inactivation of CDK2 is synthetically lethal to MYCN over-expressing cancer cells

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Molenaar, Jan J.; Ebus, Marli E.; Geerts, Dirk; Koster, Jan; Lamers, Fieke; Valentijn, Linda J.; Westerhout, Ellen M.; Versteeg, Rogier; Caron, Huib N.

2009-01-01

Two genes have a synthetically lethal relationship when the silencing or inhibiting of 1 gene is only lethal in the context of a mutation or activation of the second gene. This situation offers an attractive therapeutic strategy, as inhibition of such a gene will only trigger cell death in tumor cells with an activated second oncogene but spare normal cells without activation of the second oncogene. Here we present evidence that CDK2 is synthetically lethal to neuroblastoma cells with MYCN amplification and over-expression. Neuroblastomas are childhood tumors with an often lethal outcome. Twenty percent of the tumors have MYCN amplification, and these tumors are ultimately refractory to any therapy. Targeted silencing of CDK2 by 3 RNA interference techniques induced apoptosis in MYCN-amplified neuroblastoma cell lines, but not in MYCN single copy cells. Silencing of MYCN abrogated this apoptotic response in MYCN-amplified cells. Inversely, silencing of CDK2 in MYCN single copy cells did not trigger apoptosis, unless a MYCN transgene was activated. The MYCN induced apoptosis after CDK2 silencing was accompanied by nuclear stabilization of P53, and mRNA profiling showed up-regulation of P53 target genes. Silencing of P53 rescued the cells from MYCN-driven apoptosis. The synthetic lethality of CDK2 silencing in MYCN activated neuroblastoma cells can also be triggered by inhibition of CDK2 with a small molecule drug. Treatment of neuroblastoma cells with roscovitine, a CDK inhibitor, at clinically achievable concentrations induced MYCN-dependent apoptosis. The synthetically lethal relationship between CDK2 and MYCN indicates CDK2 inhibitors as potential MYCN-selective cancer therapeutics. PMID:19525400

UV-induced lethal sectoring and pure mutant clones in yeast.

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Hannan, M A; Duck, P; Nasim, A

1976-08-01

The induction of lethal sectoring and pure mutant clones by ultraviolet light has been studied in a homogeneous G1 population of Saccharomyces cerevisiae grown in a normal growth medium. At the lowest UV dose of 250 ergs, which corresponds to a shoulder in the survival curve, all mutants appeared as pure clones. At higher doses the frequency of mosaic mutants progressively increased. These results indicate a relationship between the highest frequency of complete mutants and the maximum repair activity. In addition, the frequency of lethal sectoring at all doses tested was too low to account for the origin of pure mutant clones.

Theories of Lethal Mutagenesis: From Error Catastrophe to Lethal Defection.

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Tejero, Héctor; Montero, Francisco; Nuño, Juan Carlos

2016-01-01

RNA viruses get extinct in a process called lethal mutagenesis when subjected to an increase in their mutation rate, for instance, by the action of mutagenic drugs. Several approaches have been proposed to understand this phenomenon. The extinction of RNA viruses by increased mutational pressure was inspired by the concept of the error threshold. The now classic quasispecies model predicts the existence of a limit to the mutation rate beyond which the genetic information of the wild type could not be efficiently transmitted to the next generation. This limit was called the error threshold, and for mutation rates larger than this threshold, the quasispecies was said to enter into error catastrophe. This transition has been assumed to foster the extinction of the whole population. Alternative explanations of lethal mutagenesis have been proposed recently. In the first place, a distinction is made between the error threshold and the extinction threshold, the mutation rate beyond which a population gets extinct. Extinction is explained from the effect the mutation rate has, throughout the mutational load, on the reproductive ability of the whole population. Secondly, lethal defection takes also into account the effect of interactions within mutant spectra, which have been shown to be determinant for the understanding the extinction of RNA virus due to an augmented mutational pressure. Nonetheless, some relevant issues concerning lethal mutagenesis are not completely understood yet, as so survival of the flattest, i.e. the development of resistance to lethal mutagenesis by evolving towards mutationally more robust regions of sequence space, or sublethal mutagenesis, i.e., the increase of the mutation rate below the extinction threshold which may boost the adaptability of RNA virus, increasing their ability to develop resistance to drugs (including mutagens). A better design of antiviral therapies will still require an improvement of our knowledge about lethal

A multivariate model of stakeholder preference for lethal cat management.

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Wald, Dara M; Jacobson, Susan K

2014-01-01

Identifying stakeholder beliefs and attitudes is critical for resolving management conflicts. Debate over outdoor cat management is often described as a conflict between two groups, environmental advocates and animal welfare advocates, but little is known about the variables predicting differences among these critical stakeholder groups. We administered a mail survey to randomly selected stakeholders representing both of these groups (n=1,596) in Florida, where contention over the management of outdoor cats has been widespread. We used a structural equation model to evaluate stakeholder intention to support non-lethal management. The cognitive hierarchy model predicted that values influenced beliefs, which predicted general and specific attitudes, which in turn, influenced behavioral intentions. We posited that specific attitudes would mediate the effect of general attitudes, beliefs, and values on management support. Model fit statistics suggested that the final model fit the data well (CFI=0.94, RMSEA=0.062). The final model explained 74% of the variance in management support, and positive attitudes toward lethal management (humaneness) had the largest direct effect on management support. Specific attitudes toward lethal management and general attitudes toward outdoor cats mediated the relationship between positive (pstakeholder intention to support non-lethal cat management. Our findings suggest that stakeholders can simultaneously perceive both positive and negative beliefs about outdoor cats, which influence attitudes toward and support for non-lethal management.

Suicide Lethality: A Concept Analysis.

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DeBastiani, Summer; De Santis, Joseph P

2018-02-01

Suicide is a significant health problem internationally. Those who complete suicide may have different behaviors and risk factors than those who attempt a non-fatal suicide. The purpose of this article is to analyze the concept of suicide lethality and propose a clear definition of the concept through the identification of antecedents, attributes, and consequences. A literature search for articles published in the English language between 1970 and 2016 was conducted using MEDLINE, the Cochrane Library, Pubmed, Psychlit, Ovid, PsycINFO, and Proquest. The bibliographies of all included studies were also reviewed to identify additional relevant citations. A concept analysis was conducted on the literature findings using six stages of Walker and Avant's method. The concept analysis differentiated between suicide, lethality, suicidal behavior, and suicide lethality. Presence of a suicide plan or a written suicide note was not found to be associated with the majority of completed suicides included in the definition of suicide lethality. There are a few scales that measure the lethality of a suicide attempt, but none that attempt to measure the concept of suicide lethality as described in this analysis. Clarifying the concept of suicide lethality encourages awareness of the possibility of different suicidal behaviors associated with different suicide outcomes and will inform the development of future nursing interventions. A clearer definition of the concept of suicide lethality will guide clinical practice, research, and policy development aimed at suicide prevention.

Inhibitory action of chlorophyllin of autosome recessive lethals induced by irradiation

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Salceda, V.M.; Pimentel, P.A.E.; Cruces, M.P.

2006-01-01

The chlorophyllin is a sodium salt of the chlorophyll that has a strong protective action of the damage induced by different agents so much physical as chemical. In Drosophila there is reported this effect in somatic cells. In contrast, in germinal cells using tests with the sexual chromosomes has not been found such inhibitory action. For this reason, in this occasion we will refer to the effect of the lethality induced in autosome chromosomes, in particular to the chromosome II of this species. For such effect groups of males of the line Canton-S its were pre-treated for 24h with or without 69 mm of CCS and later on treaties with or without 40 Gy of gamma irradiation. The males were then subjected to the technical Cy L / Pm for the detection of recessive lethals. In the third generation the respective counts of the descendant of each one of them to determine the corresponding categories for each extracted chromosome were made. To be mendelian crosses it is expected for a normal chromosome a proportion 2:1 of individuals with genotype Cy L / +: +/+. The absence of individuals +/+ it is indicative of a lethal gene, until 10% of these individuals of each male's total descendant, it is considered that is carrying of a semi lethal gene. The sum of lethal and semi lethals constitutes the category detrimental. The obtained results indicated that the pre-treatment with CCS reduces in a significant way the frequency of induced lethals by 40 Gy of gamma rays. The fact that an effect inhibitor has not been observed in the test of recessive lethal bound to the sex obtained previously, it contrasts with the effect observed in the chromosome II, results of this study and with the one observed in the chromosome III in somatic cells. The above-mentioned shows a differential action of the CCS between sexual chromosomes and autosomal before the effect of the gamma radiation. At the moment we don't have an explanation to these evidences. To evaluate the action of the chlorophyllin

Impulsivity, aggression and brain structure in high and low lethality suicide attempters with borderline personality disorder.

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Soloff, Paul; White, Richard; Diwadkar, Vaibhav A

2014-06-30

Impulsivity and aggressiveness are trait dispositions associated with the vulnerability to suicidal behavior across diagnoses. They are associated with structural and functional abnormalities in brain networks involved in regulation of mood, impulse and behavior. They are also core characteristics of borderline personality disorder (BPD), a disorder defined, in part, by recurrent suicidal behavior. We assessed the relationships between personality traits, brain structure and lethality of suicide attempts in 51 BPD attempters using multiple regression analyses on structural MRI data. BPD was diagnosed by the Diagnostic Interview for Borderline Patients-revised, impulsivity by the Barratt Impulsiveness Scale (BIS), aggression by the Brown-Goodwin Lifetime History of Aggression (LHA), and high lethality by a score of 4 or more on the Lethality Rating Scale (LRS). Sixteen High Lethality attempters were compared to 35 Low Lethality attempters, with no significant differences noted in gender, co-morbidity, childhood abuse, BIS or LHA scores. Degree of medical lethality (LRS) was negatively related to gray matter volumes across multiple fronto-temporal-limbic regions. Effects of impulsivity and aggression on gray matter volumes discriminated High from Low Lethality attempters and differed markedly within lethality groups. Lethality of suicide attempts in BPD may be related to the mediation of these personality traits by specific neural networks. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Comparative studies of dose-response curves for recessive lethal mutations induced by ethylnitrosourea in spermatogonia and in spermatozoa of Drosophila melanogaster

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Yoshikawa, I.; Ayaki, T.; Ohshima, K.

1984-01-01

Induction of recessive lethal mutation by N-ethyl-N-nitrosourea (ENU) was studied for the second chromosome of spermatogonia and spermatozoa in Drosophila melanogaster. ENU (0.03, 0.3, and 1.0 mM) was given to flies by dissolving it in feeding sucrose solution. When plotted against absorbed doses of ENU, the observed frequencies to recessive lethals showed a linear relationship for induction in spermatozoa but a sigmoidal relationship for induction in spermatogonia. These results suggest that in spermatogonia ENU-induced mutational damage is more repairable in a lower dose range of ENU. Mosaic lethal mutations were induced by ENU but not in spermatogonia.

The organisational structure of protein networks: revisiting the centrality-lethality hypothesis.

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Raman, Karthik; Damaraju, Nandita; Joshi, Govind Krishna

2014-03-01

Protein networks, describing physical interactions as well as functional associations between proteins, have been unravelled for many organisms in the recent past. Databases such as the STRING provide excellent resources for the analysis of such networks. In this contribution, we revisit the organisation of protein networks, particularly the centrality-lethality hypothesis, which hypothesises that nodes with higher centrality in a network are more likely to produce lethal phenotypes on removal, compared to nodes with lower centrality. We consider the protein networks of a diverse set of 20 organisms, with essentiality information available in the Database of Essential Genes and assess the relationship between centrality measures and lethality. For each of these organisms, we obtained networks of high-confidence interactions from the STRING database, and computed network parameters such as degree, betweenness centrality, closeness centrality and pairwise disconnectivity indices. We observe that the networks considered here are predominantly disassortative. Further, we observe that essential nodes in a network have a significantly higher average degree and betweenness centrality, compared to the network average. Most previous studies have evaluated the centrality-lethality hypothesis for Saccharomyces cerevisiae and Escherichia coli; we here observe that the centrality-lethality hypothesis hold goods for a large number of organisms, with certain limitations. Betweenness centrality may also be a useful measure to identify essential nodes, but measures like closeness centrality and pairwise disconnectivity are not significantly higher for essential nodes.

Passive dosing of polycyclic aromatic hydrocarbon (PAH) mixtures to terrestrial springtails: linking mixture toxicity to chemical activities, equilibrium lipid concentrations, and toxic units.

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Schmidt, Stine N; Holmstrup, Martin; Smith, Kilian E C; Mayer, Philipp

2013-07-02

A 7-day mixture toxicity experiment with the terrestrial springtail Folsomia candida was conducted, and the effects were linked to three different mixture exposure parameters. Passive dosing from silicone was applied to tightly control exposure levels and compositions of 12 mixture treatments, containing the polycyclic aromatic hydrocarbons (PAHs) naphthalene, phenanthrene, and pyrene. Springtail lethality was then linked to sum chemical activities (∑a), sum equilibrium lipid concentrations (∑C(lipid eq.)), and sum toxic units (∑TU). In each case, the effects of all 12 mixture treatments could be fitted to one sigmoidal exposure-response relationship. The effective lethal chemical activity (La50) of 0.027 was well within the expected range for baseline toxicity of 0.01-0.1. Linking the effects to the lipid-based exposure parameter yielded an effective lethal concentration (LC(lipid eq 50)) of 133 mmol kg(-1) lipid in good correspondence with the lethal membrane burden for baseline toxicity (40-160 mmol kg(-1) lipid). Finally, the effective lethal toxic unit (LTU50) of 1.20 was rather close to the expected value of 1. Altogether, passive dosing provided tightly controlled mixture exposure in terms of both level and composition, while ∑a, ∑C(lipid eq.), and ∑TU allowed baseline toxicity to be linked to mixture exposure.

Plasma microRNA profiles distinguish lethal injury in acetaminophen toxicity: A research study

Institute of Scientific and Technical Information of China (English)

Jeanine Ward; Shashi Bala; Jan Petrasek; Gyongyi Szabo

2012-01-01

AIM:To investigate plasma microRNA (miRNA) profiles indicative of hepatotoxicity in the setting of lethal acetaminophen (APAP) toxicity in mice.METHODS:Using plasma from APAP poisoned mice,either lethally (500 mg/kg) or sublethally (150 mg/kg) dosed,we screened commercially available murine microRNA libraries (SABiosciences,Qiagen Sciences,MD) to evaluate for unique miRNA profiles between these two dosing parameters.RESULTS:We distinguished numerous,unique plasma miRNAs both up- and downregulated in lethally compared to sublethally dosed mice.Of note,many of the greatest up- and downregulated miRNAs,namely 574-5p,466g,466f-3p,375,29c,and 148a,have been shown to be associated with asthma in prior studies.Interestingly,a relationship between APAP and asthma has been previously well described in the literature,with an as yet unknown mechanism of pathology.There was a statistically significant increase in alanine aminotransferase levels in the lethal compared to sublethal APAP dosing groups at the 12 h time point (P ＜0.001).There was 90％ mortality in the lethally compared to sublethally dosed mice at the 48 h time point (P =0.011).CONCLUSION:We identified unique plasma miRNAs both up- and downregulated in APAP poisoning which are correlated to asthma development.

Hematologic syndrome in man modeled from mammalian lethality

International Nuclear Information System (INIS)

Jones, T.D.

1981-01-01

Data on acute radiation lethality due to failure of the hematologic system in rats, mice, dogs, swine, monkeys and man are analyzed. Based on the available data, the mortality incidences for 1-100% levels can be computed directly if one has only an estimate of the dose lethal to 50% of the population (LD 50 ) for the mammalian strain and radiation environment of interest. The sole restriction is that the dose profile to the marrow be moderately uniform. If an LD 50 for any exposure situation has been measured, then one can readily scale to any desired situation through implicit-biological and empirical-physical relationships. The LD 50 for man, exposed to an isotropic cloud of photons, and knowledge of the bone-marrow dose profiles readily permit evaluation of the model for other levels of human mortality from different irradiating particles, partial body irradiation and spatially dependent and/or mixed radiation environments. (author)

Lethal and mutagenic effects of radiation and chemicals on cultured fish cells derived the erythrophoroma of goldfish (Carassius auratus)

Energy Technology Data Exchange (ETDEWEB)

Mitani, H. (Tokyo Univ. (Japan). Inst. of Zoology)

1983-01-01

GEM 199 cells derived from an eryhtrophoroma of goldfish (Carassius auratus), which had a high plating efficiency, were used to investigate the lethal and mutational effects of radiations (UV and ..gamma..-rays) and chemicals (4NQO and MNNG). The cells were more resistant to rays than mammalian cells and CAF-MM1 cells derived from the normal fin tissue of goldfish. They were also more resistant to UV-irradiation than CAF-MM1 cells. Photoreactivation after UV-irradiation was present in GEM 199 cells for both survival and mutation. The initial shoulder of the survival curve of UV-irradiated cells was reduced greatly by caffeine, suggesting a high activity of the post-replication repair. The spontaneous mutation frequency to ouabain resistance was 1-5x10/sup -6/ clones per viable cell. MNNG was effective in inducing ouabain-resistant mutation, while 4NQO and ..gamma..-rays did not induce mutation.

Induction of dominant lethal mutations by alkylating agnets in germ-cells of the silkworm, Bombyx mori

International Nuclear Information System (INIS)

Murota, Tetsuo; Murakami, Akio.

1977-01-01

The comparison of the intensity of activity was made by measuring radiation equivalent chemical (REC) dose in the experiment of the induction of dominant lethal mutation, using the germ cells of pupae five days before the moths will be hatched. The alkylating agents employed in the experiment are methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS), diethyl sulfate (DSC) and mitomycine-C (MC). X-ray irradiation was employed in order to indicate the capability of inducing mutation of the alkylating agents with the radiation equivalent chemical dose (REC dose). The dose-hatchability curves for the alkylating agents showed sigmoidal fashion as observed in X-ray, regardless of germ cells. The REC value at LD (50) was estimated by comparing the relative mutagenic capability of these chemicals. In sperm, EMS and DES with concentration of 1.0 x 10 -7 M/g showed the same lethality as about 2.3 kR and 0.6 kR of X-ray. However, no significant reduction of embryonic lethality after the treatment of pupae with MC (up to 2.1 x 10 -7 M/g) and MMS (up to 1.0 x 10 -6 M/g) was observed. As the results, the order of mutagenic effectiveness was as follows: EMS>DES>MMS approximately equal to MC. When oocytes in the mid-pupae were treated with MMS, EMS and MC with concentration of 1.0 x 10 -7 M/g, MMS and EMS showed the same effects as 12.8 kR and 0.6 kR. Surprisingly, MC showed the same lethality as 232.3 kR. This extremely high sensitivity of oocytes to MC may be ascribed to the inhibiting effect of the drug on the meiotic division. (Iwakiri, K.)

Inductions of reproduction and population growth in the generalist predator Cyrtorhinus lividipennis (Hemiptera: Miridae) exposed to sub-lethal concentrations of insecticides.

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Lu, Weiwei; Xu, Qiujing; Zhu, Jun; Liu, Chen; Ge, Linquan; Yang, Guoqing; Liu, Fang

2017-08-01

The miridbug, Cyrtorhinus lividipennis, is a significant predacious enemy of rice planthoppers. The effects of sub-lethal concentrations of triazophos, deltamethrin and imidacloprid on fecundity, egg hatchability, expression levels of genes associated with reproduction, and population growth in C. lividipennis were investigated. The fecundities for three pair combinations (♀ c × ♂ t , ♀ t × ♂ c and ♀ t × ♂ t ) treated with sub-lethal concentrations of the insecticides triazophos, deltamethrin and imidacloprid (LC 10 and LC 20 ) showed a significant increase compared to the untreated pairs (♀ c × ♂ c ). However, sub-lethal concentration treatments did not affect the egg hatchability. The ClVg expression levels of female adults exposed to triazophos, deltamethrin and imidacloprid (LC 20 ) increased by 52.6, 48.9 and 91.2%, respectively. The ClSPATA13 expression level of adult males exposed to triazophos, deltamethrim and imidacloprid (LC 20 ) increased by 80.7, 41.3 and 48.3%, respectively. Furthermore, sub-lethal concentrations of insecticides (LC 20 ) caused increased population numbers in C. lividipennis. Sub-lethal concentrations of triazophos, deltamethrin and imidacloprid stimulated reproduction and enhanced population growth of C. lividipennis. The reproductive stimulation might result from the up-regulation of ClVg or ClSPATA13. These findings may be useful in mediating populations of planthoppers. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Factors influencing circadian rhythms in acetaminophen lethality.

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Schnell, R C; Bozigian, H P; Davies, M H; Merrick, B A; Park, K S; McMillan, D A

1984-01-01

Experiments were conducted to examine the effects of changes in lighting schedules and food consumption on circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice. Under a normal lighting schedule (light: 06.00-18.00 h), male mice exhibited a circadian rhythm in acetaminophen lethality (peak: 18.00 h; nadir: 06.00, 10.00 h) and an inverse rhythm in hepatic glutathione concentrations (peak: 06.00, 10.00 h; nadir: 18.00 h). Under a reversed lighting schedule (light: 18.00-06.00 h) the glutathione rhythm was reversed and the rhythm in acetaminophen lethality was altered showing greater sensitivity to the drug. Under continuous light, there was a shift in the acetaminophen lethality and the hepatic glutathione rhythms. Under continuous dark, both rhythms were abolished. Under a normal lighting regimen, hepatic glutathione levels were closely correlated with food consumption; i.e., both were increased during the dark phase and decreased during the light phase. Fasting the mice for 12 h abolished the rhythms in acetaminophen lethality and hepatic glutathione levels; moreover, the lethality was increased and the hepatic glutathione levels were decreased. These experiments show that both lighting schedules and feeding can alter the circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice.

Relationship of DNA repair and chromosome aberrations to potentially lethal damage repair in X-irradiated mammalian cells

International Nuclear Information System (INIS)

Fornace, A.J. Jr.; Nagasawa, H.; Little, J.B.

1980-01-01

By the alkaline elution technique, the repair of x-ray-induced DNA single strand breaks and DNA-protein cross-links was investigated in stationary phase, contact-inhibited mouse cells. During the first hour of repair, approximately 90% of x-ray induced single strand breaks were rejoined whereas most of the remaining breaks were rejoined more slowly during the next 5 h. The number of residual non-rejoined single strand breaks was approximately proportional to the x-ray dose at early repair times. DNA-protein cross-links were removed at a slower rate - T 1/2 approximately 10 to 12 h. Cells were subcultured at low density at various times after irradiation and scored for colony survival, and chromosome aberrations in the first mitosis after sub-culture. Both cell lethality and the frequency of chromosome aberrations decreased during the first several hours of repair, reaching a minimum level by 6 h; this decrease correlated temporally with the repair of the slowly rejoining DNA strand breaks. The possible relationship of DNA repair to changes in survival and chromosome aberrations is discussed

Evaluating the lethal and pre-lethal effects of a range of fungi against adult Anopheles stephensi mosquitoes

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Blanford Simon

2012-11-01

Full Text Available Abstract Background Insecticide resistance is seriously undermining efforts to eliminate malaria. In response, research on alternatives to the use of chemical insecticides against adult mosquito vectors has been increasing. Fungal entomopathogens formulated as biopesticides have received much attention and have shown considerable potential. This research has necessarily focused on relatively few fungal isolates in order to ‘prove concept’. Further, most attention has been paid to examining fungal virulence (lethality and not the other properties of fungal infection that might also contribute to reducing transmission potential. Here, a range of fungal isolates were screened to examine variation in virulence and how this relates to additional pre-lethal reductions in feeding propensity. Methods The Asian malaria vector, Anopheles stephensi was exposed to 17 different isolates of entomopathogenic fungi belonging to species of Beauveria bassiana, Metarhizium anisopliae, Metarhizium acridum and Isaria farinosus. Each isolate was applied to a test substrate at a standard dose rate of 1×109 spores ml-1 and the mosquitoes exposed for six hours. Subsequently the insects were removed to mesh cages where survival was monitored over the next 14 days. During this incubation period the mosquitoes’ propensity to feed was assayed for each isolate by offering a feeding stimulant at the side of the cage and recording the number probing. Results and conclusions Fungal isolates showed a range of virulence to A. stephensi with some causing >80% mortality within 7 days, while others caused little increase in mortality relative to controls over the study period. Similarly, some isolates had a large impact on feeding propensity, causing >50% pre-lethal reductions in feeding rate, whereas other isolates had very little impact. There was clear correlation between fungal virulence and feeding reduction with virulence explaining nearly 70% of the variation in

Lethal and sub-lethal effects of five pesticides used in rice farming on the earthworm Eisenia fetida

NARCIS (Netherlands)

Rico, Andreu; Sabater, Consuelo; Castillo, María Ángeles

2016-01-01

The toxicity of five pesticides typically used in rice farming (trichlorfon, dimethoate, carbendazim, tebuconazole and prochloraz) was evaluated on different lethal and sub-lethal endpoints of the earthworm Eisenia fetida. The evaluated endpoints included: avoidance behaviour after an exposure

Lethal Epistaxis.

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Byard, Roger W

2016-09-01

Epistaxis or nosebleed refers to bleeding from the nostrils, nasal cavity, or nasopharynx. Occasional cases may present with torrential lethal hemorrhage. Three cases are reported to demonstrate particular features: Case 1: A 51-year-old woman with lethal epistaxis with no obvious bleeding source; Case 2: A 77-year-old man with treated nasopharyngeal carcinoma who died from epistaxis arising from a markedly neovascularized tumor bed; Case 3: A 2-year-old boy with hemophilia B who died from epistaxis with airway obstruction in addition to gastrointestinal bleeding. Epistaxis may be associated with trauma, tumors, vascular malformations, bleeding diatheses, infections, pregnancy, endometriosis, and a variety of different drugs. Careful dissection of the nasal cavity is required to locate the site of hemorrhage and to identify any predisposing conditions. This may be guided by postmortem computerized tomographic angiography (PCTA). Despite careful dissection, however, a source of bleeding may never be identified. © 2016 American Academy of Forensic Sciences.

The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques: A Systematic Review of the Lethal Dose Response Relationship.

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MacVittie, Thomas J; Farese, Ann M; Jackson, William

2015-11-01

Well characterized animal models that mimic the human response to potentially lethal doses of radiation are required to assess the efficacy of medical countermeasures under the criteria of the U.S. Food and Drug Administration "animal rule." Development of a model requires the determination of the radiation dose response relationship and time course of mortality and morbidity across the hematopoietic acute radiation syndrome. The nonhuman primate, rhesus macaque, is a relevant animal model that may be used to determine the efficacy of medical countermeasures to mitigate major signs of morbidity and mortality at selected lethal doses of total body irradiation. A systematic review of relevant studies that determined the dose response relationship for the hematopoietic acute radiation syndrome in the rhesus macaque relative to radiation quality, dose rate, and exposure uniformity has never been performed. The selection of data cohorts was made from the following sources: Ovid Medline (1957-present), PubMed (1954-present), AGRICOLA (1976-present), Web of Science (1954-present), and U.S. HHS REPORT (2002 to present). The following terms were used: Rhesus, total body-irradiation, total body x irradiation, TBI, irradiation, gamma radiation, hematopoiesis, LD50/60, Macaca mulatta, whole-body irradiation, nonhuman primate, NHP, monkey, primates, hematopoietic radiation syndrome, mortality, and nuclear radiation. The reference lists of all studies, published and unpublished, were reviewed for additional studies. The total number of hits across all search sites was 3,001. There were a number of referenced, unpublished, non-peer reviewed government reports that were unavailable for review. Fifteen studies, 11 primary (n = 863) and four secondary (n = 153) studies [n = 1,016 total nonhuman primates (NHP), rhesus Macaca mulatta] were evaluated to provide an informative and consistent review. The dose response relationships (DRRs) were determined for uniform or non-uniform total

Survival of bone marrow-engrafted mice subsequent to protection from lethal radiation by WR 2721

International Nuclear Information System (INIS)

Kinnamon, K.E.; Ketterling, L.L.; Ledney, G.D.; Lorenz, G.B.; Mioduszewski, R.J.; Stampfli, H.F.

1980-01-01

For the first time data are presented for animals treated with bone marrow cells after lethal radiation exposure while protected with WR 2721 (the single radioprotective chemical compound with the highest known dose reduction factor). The LD 50 30 (lethal dose to 50% in 30 days) for mice exposed to whole-body 60 Co radiation was elevated from 824 +- 8 rad in unprotected and untreated mice to (a) 1181 +- 33 rad in animals which received syngeneic bone marrow cells after exposure; (b) 1342 +- 27 rad in animals which received WR 2721 before radiation exposure; and (c) 1608 +- 33 rad in animals receiving both the radioprotective agent before exposure and bone marrow engraftment after exposure

Lethal congenital contracture syndrome (LCCS) and other lethal arthrogryposes in Finland--an epidemiological study.

Science.gov (United States)

Pakkasjärvi, Niklas; Ritvanen, Annukka; Herva, Riitta; Peltonen, Leena; Kestilä, Marjo; Ignatius, Jaakko

2006-09-01

Arthrogryposis multiplex congenita is a heterogeneous group of disorders characterized by multiple contractures with an estimated frequency of 1 in 3,000 births. With improving diagnostic methods, increasing numbers of fetuses with arthrogryposis are found. The pathogenetic mechanisms are relatively well known but the epidemiology and genetics of the prenatally lethal forms of arthrogryposis are less well known. In this study we collected all cases of a multiple contractures diagnosed in Finland during 1987-2002 including live born infants, stillbirths, and terminated pregnancies. Ninety-two cases of 214 suffered intrauterine demise (68 selective pregnancy terminations and 24 stillbirths) and 58 died in infancy. In 141 out of these cases the diagnosis could be included within lethal arthrogryposes, with a prevalence of 1 in 6,985 (1.43/10,000) births. Of these, 59 had spinal cord pathology at autopsy and thus were of neurogenic origin. Thirty-nine cases had lethal congenital contracture syndrome (LCCS) clinically characterized by total immobility of the fetus at all ultrasound examinations (12 weeks or later), multiple joint contractures in both upper and lower limbs, hydrops, and fetal death before the 32nd week of pregnancy. LCCS is noted as a unique Finnish disorder with a prevalence of 1 in 25,250 (0.40/10,000) births and is a major cause of lethal arthrogryposis in Finland.

Cytoplasmic superoxide dismutase and catalase activity and resistance to radiation lethality in murine tumor cells

International Nuclear Information System (INIS)

Davy, C.A.; Tesfay, Z.; Jones, J.; Rosenberg, R.C.; McCarthy, C.; Rosenberg, S.O.

1986-01-01

Reduced species of molecular oxygen are produced by the interaction of ionizing radiation with aqueous solutions containing molecular oxygen. The enzymes catalase and superoxide dismutase (SOD) are thought to function in vivo as scavengers of metabolically produced peroxide and superoxide respectively. SOD has been shown to protect against the lethal effects of ionizing radiation in vitro and in vivo. The authors have investigated the relationship between the cytosolic SOD catalase content and the sensitivity to radiation lethality of a number of murine cell lines (402AX, EL-4, MB-2T3, MB-4, MEL, P-815, SAI, SP-2, and SV-3T3). K/sub i/(CN - ) for murine Cu-Zn-SOD was determined to be 6.8 x 10 -6 M. No cytosolic Mn-SOD activity was found in any of the cell lines studied. No correlation was found between the cytosolic Cu-Zn-SOD or cytosolic catalase activity and the resistance to radiation lethality or the murine cell lines studied

Lethal coalitionary aggression and long-term alliance formation among Yanomamö men.

Science.gov (United States)

Macfarlan, Shane J; Walker, Robert S; Flinn, Mark V; Chagnon, Napoleon A

2014-11-25

Some cross-cultural evidence suggests lethal coalitionary aggression in humans is the product of residence and descent rules that promote fraternal interest groups, i.e., power groups of coresident males bonded by kinship. As such, human lethal coalitions are hypothesized to be homologous to chimpanzee (Pan troglodytes) border patrols. However, humans demonstrate a unique metagroup social structure in which strategic alliances allow individuals to form coalitions transcending local community boundaries. We test predictions derived from the fraternal interest group and strategic alliance models using lethal coalition data from a lowland South American population, the Yanomamö. Yanomamö men who kill an enemy acquire a special status, termed unokai. We examine the social characteristics of co-unokais or men who jointly kill others. Analyses indicate co-unokais generally are (i) from the same population but from different villages and patrilines, (ii) close age mates, and (iii) maternal half-first cousins. Furthermore, the incident rate for co-unokai killings increases if men are similar in age, from the same population, and from different natal communities. Co-unokais who have killed more times in the past and who are more genetically related to each other have a higher probability of coresidence in adulthood. Last, a relationship exists between lethal coalition formation and marriage exchange. In this population, internal warfare unites multiple communities, and co-unokais strategically form new residential groups and marriage alliances. These results support the strategic alliance model of coalitionary aggression, demonstrate the complexities of human alliance formation, and illuminate key differences in social structure distinguishing humans from other primates.

The role of cell progression in potentiation of radiation lethality by hyperthermia and by chemical means

International Nuclear Information System (INIS)

Djordjevic, B.; Lange, C.S.

1984-01-01

Aerobic stationary dense cultures of HeLa cells show very little potentiation of radiation lethality when irradiated cells are incubated with procaine HCl for two hours at 37 0 C, but if cells are diluted in fresh medium after irradiation and incubated for two hours with procaine, a high degree of radiopotentiation is obtained. This effect is not cell density dependent, since the addition of heavily irradiated cells to achieve comparable densities did not diminish lethality in the diluted culture. Procaine radiopotentiation at 37 0 C could be prevented by simultaneous administration with procaine of the protein synthesis inhibitor cycloheximide. Since cycloheximide inhibits cell cycle progression (with block points in G1 and G2) progression is strongly implicated in the phenomenon of radiopotentiation. Cell progression may be also involved in hyperthermic radiopotentiation: adding cycloheximide during heating of irradiated cells at 41 0 C for two hours increased survival. This effect of cycloheximide is even more pronounced in cells also treated with procaine during heating, thus diminishing the interaction of heat and procaine in radiopotentiation. Data pertaining to cell progression in synchronous cultures of HeLa cells under various treatment conditions are presented and discussed

DNA polymerase I is crucial for the repair of potentially lethal damage caused by the indirect effects of X irradiation in Escherichia coli

International Nuclear Information System (INIS)

Billen, D.

1985-01-01

The radiosensitivity of an Escherichia coli mutant deficient in DNA polymerase I was measured in the presence of OH radical scavengers. The extreme X-ray sensitivity of the mutant could be abolished by OH radical scavengers if a sufficiently high level of radioprotector was present. There was a direct correlation between the OH radical scavenging activity of the chemicals tested (NO 2 - , n-butanol, glycerol, t-amyl alcohol, and t-butanol) and their protective ability. The author interprets the data as showing that the indirect actions of X rays (primarily OH radicals) result in major damage to the bacterial DNA which in large part consists of potentially lethal lesions. This potentially lethal damage is repaired through an enzymatic pathway requiring DNA polymerase I. I. In the mutant lacking DNA polymerase I, these potentially lethal lesions are expressed as cell lethality

Structure activity relationships to assess new chemicals under TSCA

Energy Technology Data Exchange (ETDEWEB)

Auletta, A.E. [Environmental Protection Agency, Washington, DC (United States)

1990-12-31

Under Section 5 of the Toxic Substances Control Act (TSCA), manufacturers must notify the US Environmental Protection Agency (EPA) 90 days before manufacturing, processing, or importing a new chemical substance. This is referred to as a premanufacture notice (PMN). The PMN must contain certain information including chemical identity, production volume, proposed uses, estimates of exposure and release, and any health or environmental test data that are available to the submitter. Because there is no explicit statutory authority that requires testing of new chemicals prior to their entry into the market, most PMNs are submitted with little or no data. As a result, EPA has developed special techniques for hazard assessment of PMN chemicals. These include (1) evaluation of available data on the chemical itself, (2) evaluation of data on analogues of the PMN, or evaluation of data on metabolites or analogues of metabolites of the PMN, (3) use of quantitative structure activity relationships (QSARs), and (4) knowledge and judgement of scientific assessors in the interpretation and integration of the information developed in the course of the assessment. This approach to evaluating potential hazards of new chemicals is used to identify those that are most in need of addition review of further testing. It should not be viewed as a replacement for testing. 4 tabs.

Cell-mediated mutagenesis and cell transformation of mammalian cells by chemical carcinogens

International Nuclear Information System (INIS)

Huberman, E.; Langenbach, R.

1977-01-01

We have developed a cell-mediated mutagenesis assay in which cells with the appropriate markers for mutagenesis are co-cultivated with either lethally irradiated rodent embryonic cells that can metabolize carcinogenic hydrocarbons or with primary rat liver cells that can metabolize chemicals carcinogenic to the liver. During co-cultivation, the reactive metabolites of the procarcinogen appear to be transmitted to the mutable cells and induce mutations in them. Assays of this type make it possible to demonstrate a relationship between carcinogenic potency of the chemicals and their ability to induce mutations in mammalian cells. In addition, by simultaneously comparing the frequencies of transformation and mutation induced in normal diploid hamster cells by benzo(a)pyrene (BP) and one of its metabolites, it is possible to estimate the genetic target size for cell transformation in vitro

Rifaximin diminishes neutropenia following potentially lethal whole-body radiation.

Science.gov (United States)

Jahraus, Christopher D; Schemera, Bettina; Rynders, Patricia; Ramos, Melissa; Powell, Charles; Faircloth, John; Brawner, William R

2010-07-01

Terrorist attacks involving radiological or nuclear weapons are a substantial geopolitical concern, given that large populations could be exposed to potentially lethal doses of radiation. Because of this, evaluating potential countermeasures against radiation-induced mortality is critical. Gut microflora are the most common source of systemic infection following exposure to lethal doses of whole-body radiation, suggesting that prophylactic antibiotic therapy may reduce mortality after radiation exposure. The chemical stability, easy administration and favorable tolerability profile of the non-systemic antibiotic, rifaximin, make it an ideal potential candidate for use as a countermeasure. This study evaluated the use of rifaximin as a countermeasure against low-to-intermediate-dose whole-body radiation in rodents. Female Wistar rats (8 weeks old) were irradiated with 550 cGy to the whole body and were evaluated for 30 d. Animals received methylcellulose, neomycin (179 mg/kg/d) or variably dosed rifaximin (150-2000 mg/kg/d) one hour after irradiation and daily throughout the study period. Clinical assessments (e.g. body weight) were made daily. On postirradiation day 30, blood samples were collected and a complete blood cell count was performed. Animals receiving high doses of rifaximin (i.e. 1000 or 2000 mg/kg/d) had a greater increase in weight from the day of irradiation to postirradiation day 30 compared with animals that received placebo or neomycin. For animals with an increase in average body weight from irradiation day within 80-110% of the group average, methylcellulose rendered an absolute neutrophil count (ANC) of 211, neomycin rendered an ANC of 334, rifaximin 300 mg/kg/d rendered an ANC of 582 and rifaximin 1000 mg/kg/d rendered an ANC of 854 (P = 0.05 for group comparison). Exposure to rifaximin after near-lethal whole-body radiation resulted in diminished levels of neutropenia.

Hyperthermic radiosensitization of synchronous Chinese hamster cells: relationship between lethality and chromosomal aberrations

International Nuclear Information System (INIS)

Dewey, W.C.; Sapareto, S.A.; Betten, D.A.

1978-01-01

Synchronous Chinese hamster cells in vitro were obtained by mitotic selection. The cells were heated at 45.5 0 C for 4 min in mitosis, 11 min in G 1 , or 7 min in S sphase and then x-irradiated immediately thereafter. Colony survival from heat alone was 0.30 to 0.45, and the frequency of chromosomal aberrations induced by heat was 0.00, 0.14, or 0.97 for heat treatments during M, G 1 , or S, respectively. As shown previously, lethality from hyperthermia alone is due to chromosomal aberrations only when the cells are heated during S phase. The log survival (D 0 /sup approximately/ = 80 rad) and aberration frequency curves for cells irradiated during mitosis were linear, and the only effect of hyperthermia was to shift the curves in accord with the effect from heat alone. Thus, hyperthermia did not radiosensitize the mitotic cells. The cells irradiated in G 1 were more resistant (D 0 /sup approximately/ = 100 rad) than those irradiated in mitosis, and the survival and aberration frequency curves both had shoulders. The primary effect of hyperthermia was to greatly reduce the shoulders of the curves and to increase the slopes by about 23%. The cells irradiated in S were the most resistant (D 0 /sup approximately/ = 140 rad), and the survival and aberration frequency curves both had large shoulders. For both end points of lethality and chromosomal aberrations, heat selectively radiosensitized S-phase cells relative to G 1 cells by removing most of the shoulder and increasing the slope by about 45%. For cells treated in G 1 or S, the increase in radiosensitization following hyperthermia can be accounted for by an increase in the frequency of chromosomal aberrations

"Human Nature": Chemical Engineering Students' Ideas about Human Relationships with the Natural World

Science.gov (United States)

Goldman, Daphne; Assaraf, Orit Ben-Zvi; Shemesh, Julia

2014-01-01

While importance of environmental ethics, as a component of sustainable development, in preparing engineers is widely acknowledged, little research has addressed chemical engineers' environmental concerns. This study aimed to address this void by exploring chemical engineering students' values regarding human-nature relationships. The study was…

15 CFR 710.6 - Relationship between the Chemical Weapons Convention Regulations and the Export Administration...

Science.gov (United States)

2010-01-01

... INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS GENERAL INFORMATION AND OVERVIEW OF THE CHEMICAL WEAPONS CONVENTION REGULATIONS (CWCR) § 710.6 Relationship between the Chemical Weapons Convention Regulations and the Export Administration Regulations, the International...

Mining of lethal recessive genetic variation in Danish cattle

DEFF Research Database (Denmark)

Das, Ashutosh

2015-01-01

in fertility. The primary objective of this PhD projekt was to identify recessive lethal gentic variants in the main Danish dairy cattle breed. Holstein-Friesian utilzing next generation sequencing (NGS) data. This study shows a potential for the use of the NGS-based reverse genetic approach in identifying...... lethal or semi-lethal recessive gentic variation...

Development of quantitative structure-activity relationship (QSAR) models to predict the carcinogenic potency of chemicals

International Nuclear Information System (INIS)

Venkatapathy, Raghuraman; Wang Chingyi; Bruce, Robert Mark; Moudgal, Chandrika

2009-01-01

Determining the carcinogenicity and carcinogenic potency of new chemicals is both a labor-intensive and time-consuming process. In order to expedite the screening process, there is a need to identify alternative toxicity measures that may be used as surrogates for carcinogenic potency. Alternative toxicity measures for carcinogenic potency currently being used in the literature include lethal dose (dose that kills 50% of a study population [LD 50 ]), lowest-observed-adverse-effect-level (LOAEL) and maximum tolerated dose (MTD). The purpose of this study was to investigate the correlation between tumor dose (TD 50 ) and three alternative toxicity measures as an estimator of carcinogenic potency. A second aim of this study was to develop a Classification and Regression Tree (CART) between TD 50 and estimated/experimental predictor variables to predict the carcinogenic potency of new chemicals. Rat TD 50 s of 590 structurally diverse chemicals were obtained from the Cancer Potency Database, and the three alternative toxicity measures considered in this study were estimated using TOPKAT, a toxicity estimation software. Though poor correlations were obtained between carcinogenic potency and the three alternative toxicity (both experimental and TOPKAT) measures for the CPDB chemicals, a CART developed using experimental data with no missing values as predictor variables provided reasonable estimates of TD 50 for nine chemicals that were part of an external validation set. However, if experimental values for the three alternative measures, mutagenicity and logP are not available in the literature, then either the CART developed using missing experimental values or estimated values may be used for making a prediction

Left ventricular function during lethal and sublethal endotoxemia in swine

International Nuclear Information System (INIS)

Goldfarb, R.D.; Nightingale, L.M.; Kish, P.; Weber, P.B.; Loegering, D.J.

1986-01-01

Previous studies suggested that after a median lethal dose (LD 50 ) of endotoxin, cardiac contractility was depressed in nonsurviving dogs. The canine cardiovascular system is unlike humans in that dogs have a hepatic vein sphincter that is susceptible to adrenergic stimulation capable of raising hepatic and splanchnic venous pressures. The authors retested the hypothesis that lethality after endotoxin administration is associated with cardiac contractile depression in pigs, because of the hepatic circulation in this species is similar to that of humans. They compared cardiac mechanical function of pigs administered a high dose (250 μg/kg) or a low dose (100 μg/kg) endotoxin by use of the slope of the end-systolic pressure-diameter relationship (ESPDR) as well as other measurements of cardiac performance. In all the pigs administered a high dose, ESPDR demonstrated a marked, time-dependent depression whereas we observed no significant ESPDR changes after low endotoxin doses. The other cardiodynamic variables were uninterpretable, due to the significant changes in heart rate, end-diastolic diameter (preload), and aortic diastolic pressure (afterload). Plasma myocardia depressant factor activity accumulated in all endotoxin-administered animals, tending to be greater in the high-dose group. In this group, both subendocardial blood flow and global function were depressed, whereas pigs administered the low dose endotoxin demonstrated slight, but nonsignificant, increases in flow and function. These observations indicate that myocardial contractile depression is associated with a lethal outcome to high doses of endotoxin. Myocardial perfusion was measured using radiolabeled microspheres infused into the left atria

[Assessment of the relationship of properties of chemical compounds and their toxicity to a unified hygienic standardization for chemicals].

Science.gov (United States)

Trushkov, V F; Perminov, K A; Sapozhnikova, V V; Ignatova, O L

2013-01-01

The connection of thermodynamic properties and parameters of toxicity of chemical substances was determined. Obtained data are used for the evaluation of toxicity and hygienic rate setting of chemical compounds. The relationship between enthalpy and toxicity of chemical compounds has been established. Orthogonal planning of the experiment was carried out in the course of the investigations. Equation of unified hygienic rate setting in combined, complex, conjunct influence on the organism is presented. Prospects of determination of toxicity and methodology of unified hygienic rate setting in combined, complex, conjunct influence on the organism are presented

Lethality of Rendang packaged in multilayer retortable pouch with sterilization process

Science.gov (United States)

Praharasti, A. S.; Kusumaningrum, A.; Frediansyah, A.; Nurhikmat, A.; Khasanah, Y.; Suprapedi

2017-01-01

Retort Pouch had become a choice to preserve foods nowadays, besides the used of the can. Both had their own advantages, and Retort Pouch became more popular for the reason of cheaper and easier to recycle. General Method usually used to estimate the lethality of commercial heat sterilization process. Lethality value wa s used for evaluating the efficacy of the thermal process. This study aimed to find whether different layers of pouch materials affect the lethality value and to find differences lethality in two types of multilayer retort pouch, PET/Aluminum Foil/Nylon/RCPP and PET/Nylon/Modified Aluminum/CPP. The result showed that the different layer arrangement was resulted different Sterilization Value (SV). PET/Nylon/Modified Aluminum/CPP had better heat penetration, implied by the higher value of lethality. PET/Nylon/Modified Aluminum/CPP had the lethality value of 6,24 minutes, whereas the lethality value of PET/Aluminum Foil/Nylon/RCPP was 3,54 minutes.

Analysis of Lethality and Malformations During Zebrafish (Danio rerio) Development.

Science.gov (United States)

Raghunath, Azhwar; Perumal, Ekambaram

2018-01-01

The versatility offered by zebrafish (Danio rerio) makes it a powerful and an attractive vertebrate model in developmental toxicity and teratogenicity assays. Apart from the newly introduced chemicals as drugs, xenobiotics also induce abnormal developmental abnormalities and congenital malformations in living organisms. Over the recent decades, zebrafish embryo/larva has emerged as a potential tool to test teratogenicity potential of these chemicals. Zebrafish responds to compounds as mammals do as they share similarities in their development, metabolism, physiology, and signaling pathways with that of mammals. The methodology used by the different scientists varies enormously in the zebrafish embryotoxicity test. In this chapter, we present methods to assess lethality and malformations during zebrafish development. We propose two major malformations scoring systems: binomial and relative morphological scoring systems to assess the malformations in zebrafish embryos/larvae. Based on the scoring of the malformations, the test compound can be classified as a teratogen or a nonteratogen and its teratogenic potential is evaluated.

[Bladder tumor lethality. Results in the autonomous community of Rioja between 1975-1991].

Science.gov (United States)

Fernández Fernández, A; Gil Fabra, J; Fernández Ruíz, M; Angulo Castellanos, M G; Blanco Martín, E; Otero Mauricio, G

1998-01-01

Between 1975-1991, a total of 557 cases of bladder carcinoma were identified in the Autonomous Community of La Rioja (CAR) which were followed up to December 1994. The overall lethality was 21.9%. 492 cases with 22.35% lethality were identified in males. In females, however, there was 65 cases with 18.46% lethality. The comparison of males and females lethality resulted in p = 0.525. Lethality between cases diagnosed within each 5-year period analyzed is: 1975-1981: 177 cases, lethality 23.72%. 1982-1986: 168 cases, lethality 30.95%. 1987-1991: 212 cases, lethality 13.20%. Between the first and the second 5-year periods, p = 0.132; between the first and third 5-year periods p = 0.007 and between the second and third 5-year periods p CAR for a 22.35% lethality. Lethality is higher in males that in females but the difference is not statistically significant. In the last 5-year period assessed, 1987-1991, a reduction of lethality from bladder neoplasms has been documented.

Humanitarian Algorithms : A Codified Key Safety Switch Protocol for Lethal Autonomy

OpenAIRE

Nyagudi, Nyagudi Musandu

2014-01-01

With the deployment of lethal autonomous weapons, there is the requirement that any such platform complies with the precepts of International Humanitarian Law. Humanitarian Algorithms[9: p. 9] ensure that lethal autonomous weapon systems perform military/security operations, within the confines of International Humanitarian Law. Unlike other existing techniques of regulating lethal autonomy this scheme advocates for an approach that enables Machine Learning. Lethal autonomous weapons must be ...

Dominant lethal effect of gamma radiation of 60Co in Biomphalaria glabrata (SAY, 1818)

International Nuclear Information System (INIS)

Tallarico, Lenita de Freitas

2003-01-01

Germ cell mutations are used in ecotoxicological studies as biomarkers of population effects and indicators of ecological changes. Biomphalaria glabrata, a freshwater mollusk, is a good experimental model for biomonitoring studies due to its biological characteristics and the ecological importance of this invertebrate group. The dominant lethal test was established in B. glabrata for the detection of germ cell mutations. Results with chemical mutagens showed that this system is efficient, specific and sensitive in the evaluation of germ cell mutations induced by reference mutagens. In this work, the dominant lethal effects of gamma radiation of 60 Co were studied. A preliminary experiment was done to establish the dose range and to estimate the chronology of spermatogenesis in B. glabrata. This estimate is possible because of the uniformity in response to ionizing radiation between germ cells at homologous stages of spermatogenesis in widely different species. In general, pre-meiotic germ cells are less sensitive to the induction of lethal dominant mutations than post-meiotic cells. This effect can be attributed to: young gametogenic cells - mitotically active - have greater repair ability from sub-lethal DNA damage and there is a selective elimination of the damaged cells. In our system: induction of lethal dominant mutations causes an increase in the frequency of malformations and, cytotoxic effect is displayed as a reduction in the crossing rates. Total duration of spermatogenesis was estimated in approximately 36 days, with the following distribution of stages: 1 to 13 days - spermatogonia, 14 to 20 days - spermatocytes, 21 to 36 days - spermatids and spermatozoa. Based on this chronology, irradiated wild-type snails with 2,5; 10 and 20Gy and crossed with non-irradiated albino snails after 7, 17, 23, 30 and 36 days. The frequencies of malformations in the heterozygous wild-type offspring of the nonirradiated albino snails were used as indicator of germ cell

Non-Lethal Weapons Program

Science.gov (United States)

Sheets Frequently Asked Questions Non-Lethal Weapons FAQs Active Denial System FAQs Human Electro -Muscular Incapacitation FAQs Related Links Business Opportunities Contact JNLWD Congressional Engagement , Wednesday, Sept 20, 2017. The Active Denial System, blunt-impact munitions, dazzling lasers, LRAD 100X

Lethal effects of selected novel pesticides on immature stages of Trichogramma pretiosum (Hymenoptera: Trichogrammatidae).

Science.gov (United States)

Khan, Muhammad Ashraf; Ruberson, John R

2017-12-01

Trichogramma pretiosum Riley is an important egg parasitoid and biological control agent of caterpillar pests. We studied the acute toxicity of 20 pesticides (14 insecticides/miticides, three fungicides and three herbicides) exposed to recommended field rates. Egg, larval, and pupal stages of the parasitoid in their hosts were dipped in formulated solutions of the pesticides and evaluated 10 days later for percentage of host eggs with holes, number of parasitoids emerged per egg with holes, and stage-specific mortality of immature as well as adult wasps within the host eggs. Seven insecticides (buprofezin, chlorantraniliprole, spirotetramat, flonicamid, flubendiamide) and miticides (spiromesifen, cyflumetofen), one herbicide (nicosulfuron), and three fungicides (myclobutanil, pyraclostrobin, trifloxystrobin + tebuconazole) caused no significant mortality to immature stages or pre-emergent adult parasitoids relative to controls. By contrast, seven insecticides/miticides (abamectin, acetamiprid, dinotefuran, fipronil, novaluron, spinetoram, tolfenpyrad) adversely affected immature and pre-emergent adult T. pretiosum, with tolfenpyrad being particularly lethal. Two herbicides had moderate (glufosinate ammonium) to severe (s-metolachlor) acute lethal effects on the immature parasitoids. This study corroborates earlier findings with adult T. pretiosum. Over half of the pesticides - and all the fungicides - tested in the current study would appear to be compatible with the use of T. pretiosum in integrated pest management programs, with respect to acute parasitoid mortality. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Psychosocial influences on prisoner suicide: a case-control study of near-lethal self-harm in women prisoners.

Science.gov (United States)

Marzano, Lisa; Hawton, Keith; Rivlin, Adrienne; Fazel, Seena

2011-03-01

We examined the psychosocial influences on female prisoner suicide by carrying out a study of near-lethal self-harm. We interviewed 60 women prisoners who had recently engaged in near-lethal self-harm (cases) and 60 others who had never carried out near-lethal acts in prison (controls) from all closed female prison establishments in England and Wales, using mixed quantitative and qualitative methods. We gathered information on socio-demographic and criminological variables, life events and childhood trauma, exposure to suicidal behaviour, contributory and precipitating factors for near-lethal self-harm, social support and psychological characteristics. While socio-demographic factors were only modestly associated with near-lethal self-harm, being on remand, in single cell accommodation, and reporting negative experiences of imprisonment were strong correlates. Recent life events and past trauma, including different forms of childhood abuse, were also significantly associated with near-lethal self-harm, as were a family history of suicide and high scores on measures of depression, aggression, impulsivity and hostility, and low levels of self-esteem and social support. Our findings underline the importance of both individual and prison-related factors for suicide in custody, and hence the need for a comprehensive approach to suicide prevention in women's prisons. Given the multiple needs of female prisoners at-risk of self-harm and suicide, complex psychosocial interventions are likely to be required, including interventions for abused and bereaved women, and initiatives to improve staff-prisoner relationships and reduce bullying. The findings of this research may provide insights into factors leading to suicidal behaviour in other forensic and institutional settings, such as detention centres and psychiatric hospitals, and may assist in developing suicide prevention policies for prisoners and other at-risk populations. Copyright © 2011 Elsevier Ltd. All rights

Test of the acute lethal toxicity of pollutants to marine fish and invertebrates

International Nuclear Information System (INIS)

1989-01-01

This reference method describes the measurement of the acute lethal toxicity of pollutants to marine animals (fish and invertebrates) by a static (non-continuous flow) method. Procedures are given for the determination of the toxicity curve (survival time-concentration relationship) and for the estimation of median lethal concentrations (LC50). The method is suitable for use with fish and macro-invertebrate species. It is not suitable for planktonic organisms nor for determining the toxicity of oil, oil dispersants or other petroleum products. Those methods are described in Reference Methods Nos. 44 and 45, respectively. The test animals are exposed, in groups of approximately ten, to each of several concentrations of the pollutant. The animals are observed, at intervals, for several days, the test solutions being renewed regularly. A record is maintained of the survival times of individual animals exposed to each concentration of pollutant. The medial survival time of each group of animals is determined from a graphical plot of the raw data after a log-probability transformation. Median survival times and their confidence limits are plotted against concentrations of test substance to give a toxicity curve. Additionally, the same experimental data can be used to estimate the median lethal concentration (LC50) of the test substance to the animals after different periods of exposure. 3 refs, 5 figs, 3 tabs

Non-Lethal Weapons: Opportunities for R&D

Science.gov (United States)

2004-12-01

during the Vietnam War. US; emulsifying agents are used in food processing, drilling fluids, cosmetics , pharmaceuticals, heavy- duty cleaners, textile...conducted in a professional manner, with no threat to public safety or the environment. 11 References [1] Fenton , G., (2001). NLW Technology Taxonomy...W.A., Mason, R.L., Collins, K.R., (2000). Non-Lethal Applicants of Slippery Substances. NDIA Non-Lethal Defense IV. [24] Fenton , G., (2000). Overview

Evaluation of effects of long term exposure on lethal toxicity with mammals.

Science.gov (United States)

Verma, Vibha; Yu, Qiming J; Connell, Des W

2014-02-01

The relationship between exposure time (LT50) and lethal exposure concentration (LC50) has been evaluated over relatively long exposure times using a novel parameter, Normal Life Expectancy (NLT), as a long term toxicity point. The model equation, ln(LT50) = aLC50(ν) + b, where a, b and ν are constants, was evaluated by plotting lnLT50 against LC50 using available toxicity data based on inhalation exposure from 7 species of mammals. With each specific toxicant a single consistent relationship was observed for all mammals with ν always mammals and then be extended to estimate toxicity at any exposure time with other mammals. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Lethal synergy involving bicyclomycin: an approach for reviving old antibiotics.

Science.gov (United States)

Malik, Muhammad; Li, Liping; Zhao, Xilin; Kerns, Robert J; Berger, James M; Drlica, Karl

2014-12-01

One way to address the growing problem of antimicrobial resistance is to revive old compounds that may have intrinsic lethal activity that is obscured by protective factors. Bicyclomycin is an old inhibitor of the Rho transcription terminator that by itself shows little rapid lethal activity. However, bicyclomycin participates in bacteriostatic synergy, which raises the possibility that conditions for lethal synergy may exist, perhaps through a suppression of protective factors. Bicyclomycin was combined with bacteriostatic inhibitors of gene expression, and bactericidal activity was measured with several cultured Gram-negative pathogens. When used alone, bicyclomycin failed to rapidly kill growing cultures of Escherichia coli; however, the additional presence of bacteriostatic concentrations of tetracycline, chloramphenicol or rifampicin led to rapid killing. Four other pathogen species, Acinetobacter baumannii, Klebsiella pneumoniae, Salmonella enterica serotype Typhimurium and Shigella dysenteriae, also exhibited enhanced killing when bicyclomycin was combined with tetracycline or rifampicin. This lethal synergy was achieved at low concentrations (slightly above the MIC) for all agents tested in combinations. Follow-up work with E. coli indicated that lethal synergy arose from a blockage of transcription elongation. Moreover, lethal synergy was reduced when bicyclomycin was added 60 min before tetracycline, suggesting that bicyclomycin induces a protective factor. The action of bicyclomycin illustrates the potential present in a largely abandoned antibacterial agent; it exhibits lethal synergy when coadministered with known, bacteriostatic inhibitors of gene expression. The identification of protective factors, which are currently uncharacterized, may reveal new ways to promote the lethal action of some old antibiotics. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved

Evaluation of effects of long term exposure on lethal toxicity with mammals

International Nuclear Information System (INIS)

Verma, Vibha; Yu, Qiming J.; Connell, Des W.

2014-01-01

The relationship between exposure time (LT 50 ) and lethal exposure concentration (LC 50 ) has been evaluated over relatively long exposure times using a novel parameter, Normal Life Expectancy (NLT), as a long term toxicity point. The model equation, ln(LT 50 ) = aLC 50 ν + b, where a, b and ν are constants, was evaluated by plotting lnLT 50 against LC 50 using available toxicity data based on inhalation exposure from 7 species of mammals. With each specific toxicant a single consistent relationship was observed for all mammals with ν always <1. Use of NLT as a long term toxicity point provided a valuable limiting point for long exposure times. With organic compounds, the Kow can be used to calculate the model constants a and v where these are unknown. The model can be used to characterise toxicity to specific mammals and then be extended to estimate toxicity at any exposure time with other mammals. -- Highlights: • Model introduces a new parameter, normal life expectancy, to explain changes in toxicity with time. • Model is innovatory as it can be used to calculate toxicity at any, particularly long exposure times. • Toxicity is influenced by normal life expectancy of the organism particularly longer exposure times. • The model was applicable to all the mammals (7 species) evaluated. • The model can be used to predict toxicity at different exposure times with untested mammals species. -- The RLE model provides a mathematical description of the change in toxicity over time for a particular chemical. This represents a major advance on the use of Haber's Rule in toxicology

Chemical radiosensitization and quality of cellular damage in bacteria exposed to gamma rays

International Nuclear Information System (INIS)

Nair, C.K.K.; Pradhan, D.S.; Sreenivasan, A.

1976-01-01

Iodoacetic acid (IAA) and N-ethylmaleimide (NEM) when present during exposure of Streptococcus faecalis cells to gamma radiation enhance radiation-induced lethality under both anoxic and aerated conditions. The changes brought about by this radiosensitization in cellular functions have been studied with a view to elucidating the mechanism responsible for the increased loss of viability. The quality of cellular damage in chemical radiosensitization was investigated by correlating survival and the biosynthetic capacity of an irradiated cell population. The relationship between surviving fraction and extent of incorporation of 3 H-thymidine into DNA was found to be unaffected regardless of whether the sensitizers (IAA or NEM) were present or absent during irradiation under anoxia. However, under the oxic condition of irradiation the survival--DNA-labeling relationship was completely different in the presence and in the absence of the sensitizers

Organic chemicals jeopardize the health of freshwater ecosystems on the continental scale.

Science.gov (United States)

Malaj, Egina; von der Ohe, Peter C; Grote, Matthias; Kühne, Ralph; Mondy, Cédric P; Usseglio-Polatera, Philippe; Brack, Werner; Schäfer, Ralf B

2014-07-01

Organic chemicals can contribute to local and regional losses of freshwater biodiversity and ecosystem services. However, their overall relevance regarding larger spatial scales remains unknown. Here, we present, to our knowledge, the first risk assessment of organic chemicals on the continental scale comprising 4,000 European monitoring sites. Organic chemicals were likely to exert acute lethal and chronic long-term effects on sensitive fish, invertebrate, or algae species in 14% and 42% of the sites, respectively. Of the 223 chemicals monitored, pesticides, tributyltin, polycyclic aromatic hydrocarbons, and brominated flame retardants were the major contributors to the chemical risk. Their presence was related to agricultural and urban areas in the upstream catchment. The risk of potential acute lethal and chronic long-term effects increased with the number of ecotoxicologically relevant chemicals analyzed at each site. As most monitoring programs considered in this study only included a subset of these chemicals, our assessment likely underestimates the actual risk. Increasing chemical risk was associated with deterioration in the quality status of fish and invertebrate communities. Our results clearly indicate that chemical pollution is a large-scale environmental problem and requires far-reaching, holistic mitigation measures to preserve and restore ecosystem health.

Indirect effects are involved in the production of potentially lethal damage in X irradiated escherichia coli

International Nuclear Information System (INIS)

Billen, D.

1985-01-01

When living cells are exposed to low LET radiation, 60 to 70% of the resulting lethality is said to be due to indirect effects. Using the OH radical scavengers: glycerol n-butanol, t-butanol, and NO/sub 2//sup -/. The authors observed that a radiosensitive E. coli K-12 mutant (W 3110 thy/sup -/ polAl/sup -/) lacking DNA polymerase 1 displays a markedly enhanced radioresistance when exposed to X rays in the presence of these chemicals. The extent of protection afforded by these chemicals correlated with their OH radical scavenging ability over the limited range of concentrations of the chemicals studied. (Only non-toxic concentrations of the chemicals were used). The presence of 2M glycerol during irradiation of the PolAl/sup -/ cells results in a survival level higher than that seen for the unprotected parent strain (W 3110 thy polA/sup +/)

Influence Analysis of Shell Material and Charge on Shrapnel Lethal Power

Directory of Open Access Journals (Sweden)

Wang Lin

2015-01-01

Full Text Available To compare the shrapnel lethal power with different shell material and charge, LS-DYNA was used to numerically simulate four kinds of shrapnel lethal power. The shell material was 58SiMn, 50SiMnVB or 40Cr, whereas the charge was RL-F. And the shell material was 58SiMn, whereas the charge was TNT. The shell rupture process and lethal power test were analyzed. The results show that, the lethal power of RL-F charge increase by 25%, 45%, 14% compared with the TNT charge, whereas the shell material was 58SiMn, 50SiMnVB, 40Cr. And then the guarantee range and lethal power can be improved by using the high explosive and changing shell material, whereas the projectile shape coefficient is invariable.

Lethal and Sub-lethal Effects of Four Insecticides on the Aphidophagous Coccinellid Adalia bipunctata (Coleoptera: Coccinellidae).

Science.gov (United States)

Depalo, Laura; Lanzoni, Alberto; Masetti, Antonio; Pasqualini, Edison; Burgio, Giovanni

2017-12-05

Conventional insecticide assays, which measure the effects of insecticide exposure on short-term mortality, overlook important traits, including persistence of toxicity or sub-lethal effects. Therefore, such approaches are especially inadequate for prediction of the overall impact of insecticides on beneficial arthropods. In this study, the side effects of four modern insecticides (chlorantraniliprole, emamectin benzoate, spinosad, and spirotetramat) on Adalia bipunctata (L.) (Coleoptera: Coccinellidae) were evaluated under laboratory conditions by exposition on treated potted plants. In addition to investigation of acute toxicity and persistence of harmful activity in both larvae and adults of A. bipunctata, demographic parameters were evaluated, to provide a comprehensive picture of the nontarget effects of these products. Field doses of the four insecticides caused detrimental effects to A. bipunctata; but in different ways. Overall, spinosad showed the best toxicological profile among the products tested. Emamectin benzoate could be considered a low-risk insecticide, but had high persistence. Chlorantraniliprole exhibited lethal effects on early instar larvae and adults, along with a long-lasting activity, instead spirotetramat showed a low impact on larval and adult mortality and can be considered a short-lived insecticide. However, demographic analysis demonstrated that chlorantraniliprole and spirotetramat caused sub-lethal effects. Our findings highlight that sole assessment of mortality can lead to underestimation of the full impact of pesticides on nontarget insects. Demographic analysis was demonstrated to be a sensitive method for detection of the sub-lethal effects of insecticides on A. bipunctata, and this approach should be considered for evaluation of insecticide selectivity. © The Author(s) 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Experiences in therapy for lethal midline granuloma

International Nuclear Information System (INIS)

Tosaka, Kaoru; Ishikawa, Takeru

1982-01-01

Four cases of the lethal midline granuloma or malignant granuloma of the nose were treated by irradiation and chemotherapy, which are generally prescribed for malignant lymphomas. Clinical, histological and laboratory examination indicated that they were the lethal midline granuloma and clearly differentiated from Wegener's granulomatosis or malignant lymphoma. All of the cases exhibited primary remission. The four cases were observed up to 38, 22, 14, and 10 months since the beginning of the therapy, showing no local or general recurrence. (author)

Back to the future: revisiting HIV-1 lethal mutagenesis

Science.gov (United States)

Dapp, Michael J.; Patterson, Steven E.; Mansky, Louis M.

2012-01-01

The concept of eliminating HIV-1 infectivity by elevating the viral mutation rate was first proposed over a decade ago, even though the general concept had been conceived earlier for RNA viruses. Lethal mutagenesis was originally viewed as a novel chemotherapeutic approach for treating HIV-1 infection in which use of a viral mutagen would over multiple rounds of replication lead to the lethal accumulation of mutations, rendering the virus population non infectious – known as the slow mutation accumulation model. There have been limitations in obtaining good efficacy data with drug leads, leaving some doubt into clinical translation. More recent studies of the APOBEC3 proteins as well as new progress in the use of nucleoside analogs for inducing lethal mutagenesis have helped to refocus attention on rapid induction of HIV-1 lethal mutagenesis in a single or limited number of replication cycles leading to a rapid mutation accumulation model. PMID:23195922

Relationships between chemical structure, mechanical properties and materials processing in nanopatterned organosilicate fins

Directory of Open Access Journals (Sweden)

Gheorghe Stan

2017-04-01

Full Text Available The exploitation of nanoscale size effects to create new nanostructured materials necessitates the development of an understanding of relationships between molecular structure, physical properties and material processing at the nanoscale. Numerous metrologies capable of thermal, mechanical, and electrical characterization at the nanoscale have been demonstrated over the past two decades. However, the ability to perform nanoscale molecular/chemical structure characterization has only been recently demonstrated with the advent of atomic-force-microscopy-based infrared spectroscopy (AFM-IR and related techniques. Therefore, we have combined measurements of chemical structures with AFM-IR and of mechanical properties with contact resonance AFM (CR-AFM to investigate the fabrication of 20–500 nm wide fin structures in a nanoporous organosilicate material. We show that by combining these two techniques, one can clearly observe variations of chemical structure and mechanical properties that correlate with the fabrication process and the feature size of the organosilicate fins. Specifically, we have observed an inverse correlation between the concentration of terminal organic groups and the stiffness of nanopatterned organosilicate fins. The selective removal of the organic component during etching results in a stiffness increase and reinsertion via chemical silylation results in a stiffness decrease. Examination of this effect as a function of fin width indicates that the loss of terminal organic groups and stiffness increase occur primarily at the exposed surfaces of the fins over a length scale of 10–20 nm. While the observed structure–property relationships are specific to organosilicates, we believe the combined demonstration of AFM-IR with CR-AFM should pave the way for a similar nanoscale characterization of other materials where the understanding of such relationships is essential.

Perinatal-lethal Gaucher disease presenting as hydrops fetalis.

Science.gov (United States)

BenHamida, Emira; Ayadi, Imene; Ouertani, Ines; Chammem, Maroua; Bezzine, Ahlem; BenTmime, Riadh; Attia, Leila; Mrad, Ridha; Marrakchi, Zahra

2015-01-01

Perinatal-lethal Gaucher disease is very rare and is considered a variant of type 2 Gaucher disease that occurs in the neonatal period. The most distinct features of perinatal-lethal Gaucher disease are non-immune hydrops fetalis. Less common signs of the disease are hepatosplenomegaly, ichthyosis and arthrogryposis. We report a case of Gaucher's disease (type 2) diagnosed in a newborn who presented with Hydrops Fetalis.

Efficient chemical-disease identification and relationship extraction using Wikipedia to improve recall.

Science.gov (United States)

Lowe, Daniel M; O'Boyle, Noel M; Sayle, Roger A

2016-01-01

Awareness of the adverse effects of chemicals is important in biomedical research and healthcare. Text mining can allow timely and low-cost extraction of this knowledge from the biomedical literature. We extended our text mining solution, LeadMine, to identify diseases and chemical-induced disease relationships (CIDs). LeadMine is a dictionary/grammar-based entity recognizer and was used to recognize and normalize both chemicals and diseases to Medical Subject Headings (MeSH) IDs. The disease lexicon was obtained from three sources: MeSH, the Disease Ontology and Wikipedia. The Wikipedia dictionary was derived from pages with a disease/symptom box, or those where the page title appeared in the lexicon. Composite entities (e.g. heart and lung disease) were detected and mapped to their composite MeSH IDs. For CIDs, we developed a simple pattern-based system to find relationships within the same sentence. Our system was evaluated in the BioCreative V Chemical-Disease Relation task and achieved very good results for both disease concept ID recognition (F1-score: 86.12%) and CIDs (F1-score: 52.20%) on the test set. As our system was over an order of magnitude faster than other solutions evaluated on the task, we were able to apply the same system to the entirety of MEDLINE allowing us to extract a collection of over 250 000 distinct CIDs. © The Author(s) 2016. Published by Oxford University Press.

Are Trp53 rescue of Brca1 embryonic lethality and Trp53/Brca1 breast cancer association related?

International Nuclear Information System (INIS)

McAllister, Kimberly A; Wiseman, Roger W

2002-01-01

Brca1 is involved in multiple biological pathways including DNA damage repair, transcriptional regulation, and cell-cycle progression. A complex pattern of interactions of Brca1 with Trp53 has also emerged. Xu and coworkers found that haploid loss of Trp53 significantly reduces the embryonic lethality observed in mice with a homozygous in-frame deletion of Brca1 exon 11. They report that widespread apoptosis correlates with the embryonic lethality resulting from this homozygous Δ11 Brca1 mutation. A mechanism responsible for Brca1-associated carcinogenesis is proposed. These experiments extend our knowledge of a complex Brca1/Trp53 relationship. However, the precise mechanisms through which Brca1 interacts with Trp53 to suppress mammary tumor formation have yet to be elucidated

X-ray induced dominant lethal mutations in mature and immature oocytes of guinea-pigs and golden hamsters

International Nuclear Information System (INIS)

Cox, B.D.; Lyon, M.F.

1975-01-01

The induction of dominant lethal mutations by doses of 100-400 rad X-rays in oocytes of the guinea-pig and golden hamster was studied using criteria of embryonic mortality. For both species higher yields were obtained from mature than from immature oocytes. Data on fertility indicated that in the golden hamster immature oocytes were more sensitive to killing by X-rays than mature oocytes but that the converse was true in the guinea-pig. The dose-response relationship for mutation to dominant lethals in pre-ovulatory oocytes of guinea-pigs and golden hamsters was linear, both when based on pre- and post-implantation loss only. The rate per unit dose was higher for the golden hamster, and the old golden hamsters were possibly slightly more sensitive than young ones

Lethal neonatal short-limbed dwarfism

International Nuclear Information System (INIS)

Kim, Ok Hwa; Yim, Chung Ik; Bahk, Yong Whee

1986-01-01

We have detailed our experiences on 6 cases of neonatal lethal short-limbed dwarfism and reviewed the articles. They include, achondrogenesis, thanatophoric dysplasia, asphyxiating thoracic dysplasia, osteogenesis imperfect a congenita, and hypophosphatasia lethals. Five babies were born alive but died soon after birth and one was a stillbirth. The main cause of failure to thrive was respiratory insufficiency. Each case was having quite characteristic radiologic findings, even if the general appearances were similar to the achondroplasts clinically. Precise diagnosis is very important for genetic counselling of the parents and alarm to them the possibility of bone dysplasias to the next offsprings. For this purpose, the radiologists play major role for the correct diagnosis. We stress that when the baby is born with short-limbed dwarfism, whole body radiogram should be taken including lateral view and postmortem radiogram is also very precious.

Lethal neonatal short-limbed dwarfism

Energy Technology Data Exchange (ETDEWEB)

Kim, Ok Hwa; Yim, Chung Ik; Bahk, Yong Whee [Catholic Medical College, Seoul (Korea, Republic of)

1986-02-15

We have detailed our experiences on 6 cases of neonatal lethal short-limbed dwarfism and reviewed the articles. They include, achondrogenesis, thanatophoric dysplasia, asphyxiating thoracic dysplasia, osteogenesis imperfect a congenita, and hypophosphatasia lethals. Five babies were born alive but died soon after birth and one was a stillbirth. The main cause of failure to thrive was respiratory insufficiency. Each case was having quite characteristic radiologic findings, even if the general appearances were similar to the achondroplasts clinically. Precise diagnosis is very important for genetic counselling of the parents and alarm to them the possibility of bone dysplasias to the next offsprings. For this purpose, the radiologists play major role for the correct diagnosis. We stress that when the baby is born with short-limbed dwarfism, whole body radiogram should be taken including lateral view and postmortem radiogram is also very precious.

Integrative Chemical-Biological Read-Across Approach for Chemical Hazard Classification

Science.gov (United States)

Low, Yen; Sedykh, Alexander; Fourches, Denis; Golbraikh, Alexander; Whelan, Maurice; Rusyn, Ivan; Tropsha, Alexander

2013-01-01

Traditional read-across approaches typically rely on the chemical similarity principle to predict chemical toxicity; however, the accuracy of such predictions is often inadequate due to the underlying complex mechanisms of toxicity. Here we report on the development of a hazard classification and visualization method that draws upon both chemical structural similarity and comparisons of biological responses to chemicals measured in multiple short-term assays (”biological” similarity). The Chemical-Biological Read-Across (CBRA) approach infers each compound's toxicity from those of both chemical and biological analogs whose similarities are determined by the Tanimoto coefficient. Classification accuracy of CBRA was compared to that of classical RA and other methods using chemical descriptors alone, or in combination with biological data. Different types of adverse effects (hepatotoxicity, hepatocarcinogenicity, mutagenicity, and acute lethality) were classified using several biological data types (gene expression profiling and cytotoxicity screening). CBRA-based hazard classification exhibited consistently high external classification accuracy and applicability to diverse chemicals. Transparency of the CBRA approach is aided by the use of radial plots that show the relative contribution of analogous chemical and biological neighbors. Identification of both chemical and biological features that give rise to the high accuracy of CBRA-based toxicity prediction facilitates mechanistic interpretation of the models. PMID:23848138

Chemical modifications of antisense morpholino oligomers enhance their efficacy against Ebola virus infection.

Science.gov (United States)

Swenson, Dana L; Warfield, Kelly L; Warren, Travis K; Lovejoy, Candace; Hassinger, Jed N; Ruthel, Gordon; Blouch, Robert E; Moulton, Hong M; Weller, Dwight D; Iversen, Patrick L; Bavari, Sina

2009-05-01

Phosphorodiamidate morpholino oligomers (PMOs) are uncharged nucleic acid-like molecules designed to inactivate the expression of specific genes via the antisense-based steric hindrance of mRNA translation. PMOs have been successful at knocking out viral gene expression and replication in the case of acute viral infections in animal models and have been well tolerated in human clinical trials. We propose that antisense PMOs represent a promising class of therapeutic agents that may be useful for combating filoviral infections. We have previously shown that mice treated with a PMO whose sequence is complementary to a region spanning the start codon of VP24 mRNA were protected against lethal Ebola virus challenge. In the present study, we report on the abilities of two additional VP24-specific PMOs to reduce the cell-free translation of a VP24 reporter, to inhibit the in vitro replication of Ebola virus, and to protect mice against lethal challenge when the PMOs are delivered prior to infection. Additionally, structure-activity relationship evaluations were conducted to assess the enhancement of antiviral efficacy associated with PMO chemical modifications that included conjugation with peptides of various lengths and compositions, positioning of conjugated peptides to either the 5' or the 3' terminus, and the conferring of charge modifications by the addition of piperazine moieties. Conjugation with arginine-rich peptides greatly enhanced the antiviral efficacy of VP24-specific PMOs in infected cells and mice during lethal Ebola virus challenge.

Radiation-induced mutagenicity and lethality in Salmonella typhimurium

International Nuclear Information System (INIS)

Isildar, M.; Bakale, G.

1983-01-01

The mutagenic and lethal effects of ionizing radiation on histidine-deficient auxotrophs of Salmonella typhimurium were studied to improve the understanding of radiation damage to DNA. The auxotrophs were divided into two groups - one which is sensitive to base-pair substitutions and another sensitive to frameshifts. These groups were composed of parent-daughter pairs in which the chemical mutagenicity enhancing plasmid, pKM101, is absent in the parent strain and present in the daughter. Co-60 #betta#-radiation and 250 kV x-rays were used to irradiate the bacteria. Irradiation of the frameshift - sensitive strains which carry the pKm101 plasmid doubled the absolute number of induced revertants whereas irradiation of the base-pair substitution sensitive strain which also carries the pKm101 plasmid produced nearly no change in the number of induced revertants. A nearly negligible effect on the mutation rate was observed for all parent strains

Lethal interpersonal violence in the Middle Pleistocene.

Directory of Open Access Journals (Sweden)

Nohemi Sala

Full Text Available Evidence of interpersonal violence has been documented previously in Pleistocene members of the genus Homo, but only very rarely has this been posited as the possible manner of death. Here we report the earliest evidence of lethal interpersonal violence in the hominin fossil record. Cranium 17 recovered from the Sima de los Huesos Middle Pleistocene site shows two clear perimortem depression fractures on the frontal bone, interpreted as being produced by two episodes of localized blunt force trauma. The type of injuries, their location, the strong similarity of the fractures in shape and size, and the different orientations and implied trajectories of the two fractures suggest they were produced with the same object in face-to-face interpersonal conflict. Given that either of the two traumatic events was likely lethal, the presence of multiple blows implies an intention to kill. This finding shows that the lethal interpersonal violence is an ancient human behavior and has important implications for the accumulation of bodies at the site, supporting an anthropic origin.

Lethal interpersonal violence in the Middle Pleistocene.

Science.gov (United States)

Sala, Nohemi; Arsuaga, Juan Luis; Pantoja-Pérez, Ana; Pablos, Adrián; Martínez, Ignacio; Quam, Rolf M; Gómez-Olivencia, Asier; Bermúdez de Castro, José María; Carbonell, Eudald

2015-01-01

Evidence of interpersonal violence has been documented previously in Pleistocene members of the genus Homo, but only very rarely has this been posited as the possible manner of death. Here we report the earliest evidence of lethal interpersonal violence in the hominin fossil record. Cranium 17 recovered from the Sima de los Huesos Middle Pleistocene site shows two clear perimortem depression fractures on the frontal bone, interpreted as being produced by two episodes of localized blunt force trauma. The type of injuries, their location, the strong similarity of the fractures in shape and size, and the different orientations and implied trajectories of the two fractures suggest they were produced with the same object in face-to-face interpersonal conflict. Given that either of the two traumatic events was likely lethal, the presence of multiple blows implies an intention to kill. This finding shows that the lethal interpersonal violence is an ancient human behavior and has important implications for the accumulation of bodies at the site, supporting an anthropic origin.

Redox biotransformation and delivery of anthracycline anticancer antibiotics: How interpretable structure-activity relationships of lethality using electrophilicity and the London formula for dispersion interaction work.

Science.gov (United States)

Pang, Siu-Kwong

2017-03-30

Quantum chemical methods and molecular mechanics approaches face a lot of challenges in drug metabolism study because of their either insufficient accuracy or huge computational cost, or lack of clear molecular level pictures for building computational models. Low-cost QSAR methods can often be carried out even though molecular level pictures are not well defined; however, they show difficulty in identifying the mechanisms of drug metabolism and delineating the effects of chemical structures on drug toxicity because a certain amount of molecular descriptors are difficult to be interpreted. In order to make a breakthrough, it was proposed that mechanistically interpretable molecular descriptors were used to correlate with biological activity to establish structure-activity plots. The mechanistically interpretable molecular descriptors used in this study include electrophilicity and the mathematical function in the London formula for dispersion interaction, and they were calculated using quantum chemical methods. The biological activity is the lethality of anthracycline anticancer antibiotics denoted as log LD50, which were obtained by intraperitoneal injection into mice. The results reveal that the plots for electrophilicity, which can be interpreted as redox reactivity of anthracyclines, can describe oxidative degradation for detoxification and reductive bioactivation for toxicity induction. The plots for the dispersion interaction function, which represent the attraction between anthracyclines and biomolecules, can describe efflux from and influx into target cells of toxicity. The plots can also identify three structural scaffolds of anthracyclines that have different metabolic pathways, resulting in their different toxicity behavior. This structure-dependent toxicity behavior revealed in the plots can provide perspectives on design of anthracycline anticancer antibiotics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Transporting Patients with Lethal Contagious Infections

National Research Council Canada - National Science Library

Swartz, Colleen

2002-01-01

.... The AIT is a unique military medical team capable of worldwide air evacuation and management of a limited number of patients who are potentially exposed to known and unknown lethal communicable...

A bacterial cocaine esterase protects against cocaine-induced epileptogenic activity and lethality.

Science.gov (United States)

Jutkiewicz, Emily M; Baladi, Michelle G; Cooper, Ziva D; Narasimhan, Diwahar; Sunahara, Roger K; Woods, James H

2009-09-01

Cocaine toxicity results in cardiovascular complications, seizures, and death and accounts for approximately 20% of drug-related emergency department visits every year. Presently, there are no treatments to eliminate the toxic effects of cocaine. The present study hypothesizes that a bacterial cocaine esterase with high catalytic efficiency would provide rapid and robust protection from cocaine-induced convulsions, epileptogenic activity, and lethality. Cocaine-induced paroxysmal activity and convulsions were evaluated in rats surgically implanted with radiotelemetry devices (N=6 per treatment group). Cocaine esterase was administered 1 minute after a lethal dose of cocaine or after cocaine-induced convulsions to determine the ability of the enzyme to prevent or reverse, respectively, the effects of cocaine. The cocaine esterase prevented all cocaine-induced electroencephalographic changes and lethality. This effect was specific for cocaine because the esterase did not prevent convulsions and death induced by a cocaine analog, (-)-2beta-carbomethoxy-3beta-phenyltropane. The esterase prevented lethality even after cocaine-induced convulsions occurred. In contrast, the short-acting benzodiazepine, midazolam, prevented cocaine-induced convulsions but not the lethal effects of cocaine. The data showed that cocaine esterase successfully degraded circulating cocaine to prevent lethality and that cocaine-induced convulsions alone are not responsible for the lethal effects of cocaine in this model. Therefore, further investigation into the use of cocaine esterase for treating cocaine overdose and its toxic effects is warranted.

A linear solvation energy relationship model of organic chemical partitioning to dissolved organic carbon.

Science.gov (United States)

Kipka, Undine; Di Toro, Dominic M

2011-09-01

Predicting the association of contaminants with both particulate and dissolved organic matter is critical in determining the fate and bioavailability of chemicals in environmental risk assessment. To date, the association of a contaminant to particulate organic matter is considered in many multimedia transport models, but the effect of dissolved organic matter is typically ignored due to a lack of either reliable models or experimental data. The partition coefficient to dissolved organic carbon (K(DOC)) may be used to estimate the fraction of a contaminant that is associated with dissolved organic matter. Models relating K(DOC) to the octanol-water partition coefficient (K(OW)) have not been successful for many types of dissolved organic carbon in the environment. Instead, linear solvation energy relationships are proposed to model the association of chemicals with dissolved organic matter. However, more chemically diverse K(DOC) data are needed to produce a more robust model. For humic acid dissolved organic carbon, the linear solvation energy relationship predicts log K(DOC) with a root mean square error of 0.43. Copyright © 2011 SETAC.

A lethal ovitrap-based mass trapping scheme for dengue control in Australia: I. Public acceptability and performance of lethal ovitraps.

Science.gov (United States)

Ritchie, S A; Rapley, L P; Williams, C; Johnson, P H; Larkman, M; Silcock, R M; Long, S A; Russell, R C

2009-12-01

We report on the first field evaluation of the public acceptability and performance of two types of lethal ovitrap (LO) in three separate trials in Cairns, Australia. Health workers were able to set standard lethal ovitraps (SLOs) in 75 and 71% of premise yards in the wet and dry season, respectively, and biodegradable lethal ovitraps (BLOs) in 93% of yards. Public acceptance, measured as retention of traps by residents, was high for both trap types, with porous (grass, soil and mulch) versus solid (tiles, concrete, wood and stone) substrates. The SLOs and the BLOs were readily acceptable to ovipositing Aedes aegypti L. (Diptera: Culicidae); the mean number of eggs/trap was 6 and 15, for the dry season and wet season SLO trial, respectively, and 15 for the BLO wet season trial. Indeed, 84-94% of premise yards had egg positive SLOs or BLOs. A high percentage of both wet and dry season SLOs (29 and 70%, respectively) and BLOs (62%) that were dry after 4 weeks were egg positive, indicating the traps had functioned. Lethal strips from SLOs and BLOs that had been exposed for 4 weeks killed 83 and 74%, respectively, of gravid Ae. aegypti in laboratory assays. These results indicate that mass trapping schemes using SLOs and BLOs are not rejected by the public and effectively target gravid Ae. aegypti. The impact of the interventions on mosquito populations is described in a companion paper.

Lethal mechanisms in gastric volvulus.

Science.gov (United States)

Omond, Kimberley J; Byard, Roger W

2017-01-01

A 55-year-old wheelchair-bound woman with severe cerebral palsy was found at autopsy to have marked distention of the stomach due to a volvulus. The stomach was viable, and filled with air and fluid and had pushed the left dome of the diaphragm upwards causing marked compression of the left lung with a mediastinal shift to the right (including the heart). There was no evidence of gastric perforation, ischaemic necrosis or peritonitis. Removal of the organ block revealed marked kyphoscoliosis. Histology confirmed the viability of the stomach and biochemistry showed no dehydration. Death in cases of acute gastric volvulus usually occurs because of compromise of the gastric blood supply resulting in ischaemic necrosis with distention from swallowed air and fluid resulting in perforation with lethal peritonitis. Hypovolaemic shock may also occur. However, the current case demonstrates an alternative lethal mechanism, that of respiratory compromise due to marked thoracic organ compression.

The lethal injection quandary: how medicine has dismantled the death penalty.

Science.gov (United States)

Denno, Deborah W

2007-10-01

On February 20, 2006, Michael Morales was hours away from execution in California when two anesthesiologists declined to participate in his lethal injection procedure, thereby halting all state executions. The events brought to the surface the long-running schism between law and medicine, raising the question of whether any beneficial connection between the professions ever existed in the execution context. History shows it seldom did. Decades of botched executions prove it. This Article examines how states ended up with such constitutionally vulnerable lethal injection procedures, suggesting that physician participation in executions, though looked upon with disdain, is more prevalent--and perhaps more necessary--than many would like to believe. The Article also reports the results of this author's unique nationwide study of lethal injection protocols and medical participation. The study demonstrates that states have continued to produce grossly inadequate protocols that severely restrict sufficient understanding of how executions are performed and heighten the likelihood of unconstitutionality. The analysis emphasizes in particular the utter lack of medical or scientific testing of lethal injection despite the early and continuous involvement of doctors but ongoing detachment of medical societies. Lastly, the Article discusses the legal developments that led up to the current rush of lethal injection lawsuits as well as the strong and rapid reverberations that followed, particularly with respect to medical involvement. This Article concludes with two recommendations. First, much like what occurred in this country when the first state switched to electrocution, there should be a nationwide study of proper lethal injection protocols. An independent commission consisting of a diverse group of qualified individuals, including medical personnel, should conduct a thorough assessment of lethal injection, especially the extent of physician participation. Second, this

Empirical complexities in the genetic foundations of lethal mutagenesis.

Science.gov (United States)

Bull, James J; Joyce, Paul; Gladstone, Eric; Molineux, Ian J

2013-10-01

From population genetics theory, elevating the mutation rate of a large population should progressively reduce average fitness. If the fitness decline is large enough, the population will go extinct in a process known as lethal mutagenesis. Lethal mutagenesis has been endorsed in the virology literature as a promising approach to viral treatment, and several in vitro studies have forced viral extinction with high doses of mutagenic drugs. Yet only one empirical study has tested the genetic models underlying lethal mutagenesis, and the theory failed on even a qualitative level. Here we provide a new level of analysis of lethal mutagenesis by developing and evaluating models specifically tailored to empirical systems that may be used to test the theory. We first quantify a bias in the estimation of a critical parameter and consider whether that bias underlies the previously observed lack of concordance between theory and experiment. We then consider a seemingly ideal protocol that avoids this bias-mutagenesis of virions-but find that it is hampered by other problems. Finally, results that reveal difficulties in the mere interpretation of mutations assayed from double-strand genomes are derived. Our analyses expose unanticipated complexities in testing the theory. Nevertheless, the previous failure of the theory to predict experimental outcomes appears to reside in evolutionary mechanisms neglected by the theory (e.g., beneficial mutations) rather than from a mismatch between the empirical setup and model assumptions. This interpretation raises the specter that naive attempts at lethal mutagenesis may augment adaptation rather than retard it.

Calcium-Sensing Receptor Tumor Expression and Lethal Prostate Cancer Progression.

Science.gov (United States)

Ahearn, Thomas U; Tchrakian, Nairi; Wilson, Kathryn M; Lis, Rosina; Nuttall, Elizabeth; Sesso, Howard D; Loda, Massimo; Giovannucci, Edward; Mucci, Lorelei A; Finn, Stephen; Shui, Irene M

2016-06-01

Prostate cancer metastases preferentially target bone, and the calcium-sensing receptor (CaSR) may play a role in promoting this metastatic progression. We evaluated the association of prostate tumor CaSR expression with lethal prostate cancer. A validated CaSR immunohistochemistry assay was performed on tumor tissue microarrays. Vitamin D receptor (VDR) expression and phosphatase and tensin homolog tumor status were previously assessed in a subset of cases by immunohistochemistry. Cox proportional hazards models adjusting for age and body mass index at diagnosis, Gleason grade, and pathological tumor node metastasis stage were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of CaSR expression with lethal prostate cancer. The investigation was conducted in the Health Professionals Follow-up Study and Physicians' Health Study. We studied 1241 incident prostate cancer cases diagnosed between 1983 and 2009. Participants were followed up or cancer-specific mortality or development of metastatic disease. On average, men were followed up 13.6 years, during which there were 83 lethal events. High CaSR expression was associated with lethal prostate cancer independent of clinical and pathological variables (HR 2.0; 95% CI 1.2-3.3). Additionally, there was evidence of effect modification by VDR expression; CaSR was associated with lethal progression among men with low tumor VDR expression (HR 3.2; 95% CI 1.4-7.3) but not in cases with high tumor VDR expression (HR 0.8; 95% CI 0.2-3.0). Tumor CaSR expression is associated with an increased risk of lethal prostate cancer, particularly in tumors with low VDR expression. These results support further investigating the mechanism linking CaSR with metastases.

Effect of lethality on the extinction and on the error threshold of quasispecies.

Science.gov (United States)

Tejero, Hector; Marín, Arturo; Montero, Francisco

2010-02-21

In this paper the effect of lethality on error threshold and extinction has been studied in a population of error-prone self-replicating molecules. For given lethality and a simple fitness landscape, three dynamic regimes can be obtained: quasispecies, error catastrophe, and extinction. Using a simple model in which molecules are classified as master, lethal and non-lethal mutants, it is possible to obtain the mutation rates of the transitions between the three regimes analytically. The numerical resolution of the extended model, in which molecules are classified depending on their Hamming distance to the master sequence, confirms the results obtained in the simple model and shows how an error catastrophe regime changes when lethality is taken in account. (c) 2009 Elsevier Ltd. All rights reserved.

Suicide Intent and Accurate Expectations of Lethality: Predictors of Medical Lethality of Suicide Attempts

Science.gov (United States)

Brown, Gregory K.; Henriques, Gregg R.; Sosdjan, Daniella; Beck, Aaron T.

2004-01-01

The degree of intent to commit suicide and the severity of self-injury were examined in individuals (N = 180) who had recently attempted suicide. Although a minimal association was found between the degree of suicide intent and the degree of lethality of the attempt, the accuracy of expectations about the likelihood of dying was found to moderate…

Lethality of patients with rheumatoid arthritis depending on adalimumab administration: imitation modeling

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D V Goryachev

2009-01-01

Full Text Available Lethality of pts with rheumatoid arthritis (RA exceeds mortality values in general population. Possibility of disease modifying anti-rheumatic drugs (DMARD influence on RA pts lethality has been widely discussed lately in scientific works. Objective. To determine possible lethality diminishment in Russian population of RA pts with one of biological drugs TNFα antagonist adalimumab. Material and methods. Model construction is based on the fact of lethality dependence on pt functional state assessed by HAQ. Model simulating progression of functional disability in pts with RA visiting medical institutions of Russia was made (RAISER study. 3 model variants for imitation of consecutive change of DMARDs including adalimumab were done. First consecution assessed DMARD change in the next chain: adalimumab-methotrexate-sulfasalazine-leflunomide-azathioprine-cyclosporine-palliative therapy. Second consecution: adalimumab administration after failure of first 3 DMARDs. Third consecution considered only change of synthetic DMARDs without adalimumab inclusion. Model imitated participation of 3000 pts in every consecution. Prognosis horizon was 12 years. Age of pts and initial HAQ distribution were get from results of epidemiological RAISER study. Calculation was done on the base of elevation of standardized lethality level (SLL in population of RA pts in average from 135% to 300%. SLL values from 80 to 320% were used depending on functional disability degree with converting to Russian values of age-specific lethality coefficient for 1999. Results. Lethality in treatment consecutions including adalimumab was significantly lower. To the end of 12th year in group not using adalimumab, using it at once and using it after 376 DMARDs respectively 65,1%, 71,6% and 71,1% of pts were still alive. Conclusion. Significant decrease of lethality with adalimumab inclusion in consecution of DMARD change during treatment of RA pts was demonstrated with imitation modeling

Inhibitory action of chlorophyllin of autosome recessive lethals induced by irradiation; Accion inhibidora de la clorofilina de letales recesivos autosonicos inducidos por irradiacion

Energy Technology Data Exchange (ETDEWEB)

Salceda, V.M.; Pimentel, P.A.E.; Cruces, M.P. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)]. e-mail: vmss@nuclear.inin.mx

2006-07-01

The chlorolin is a sodium salt of the chlorophyll that has a strong protective action of the damage induced by different agents so much physical as chemical. In Drosophila there is reported this effect in somatic cells. In contrast, in germinal cells using tests with the sexual chromosomes has not been found such inhibitory action. For this reason, in this occasion we will refer to the effect of the lethality induced in autosome chromosomes, in particular to the chromosome II of this species. For such effect groups of males of the line Canton-S its were pre-treated for 24h with or without 69 mm of CCS and later on treaties with or without 40 Gy of gamma irradiation. The males were then subjected to the technical Cy L / Pm for the detection of recessive lethals. In the third generation the respective counts of the descendant of each one of them to determine the corresponding categories for each extracted chromosome were made. To be mendelian crosses it is expected for a normal chromosome a proportion 2:1 of individuals with genotype Cy L / +: +/+. The absence of individuals +/+ it is indicative of a lethal gene, until 10% of these individuals of each male's total descendant, it is considered that is carrying of a semi lethal gene. The sum of lethal and semi lethals constitutes the category detrimental. The obtained results indicated that the pre-treatment with CCS reduces in a significant way the frequency of induced lethals by 40 Gy of gamma rays. The fact that an effect inhibitor has not been observed in the test of recessive lethal bound to the sex obtained previously, it contrasts with the effect observed in the chromosome II, results of this study and with the one observed in the chromosome III in somatic cells. The above-mentioned shows a differential action of the CCS between sexual chromosomes and autosomal before the effect of the gamma radiation. At the moment we don't have an explanation to these evidences. To evaluate the action of the

Inhibitory action of chlorophyllin of autosome recessive lethals induced by irradiation; Accion inhibidora de la clorofilina de letales recesivos autosonicos inducidos por irradiacion

Energy Technology Data Exchange (ETDEWEB)

Salceda, V M; Pimentel, P A.E.; Cruces, M P [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

2006-07-01

The chlorolin is a sodium salt of the chlorophyll that has a strong protective action of the damage induced by different agents so much physical as chemical. In Drosophila there is reported this effect in somatic cells. In contrast, in germinal cells using tests with the sexual chromosomes has not been found such inhibitory action. For this reason, in this occasion we will refer to the effect of the lethality induced in autosome chromosomes, in particular to the chromosome II of this species. For such effect groups of males of the line Canton-S its were pre-treated for 24h with or without 69 mm of CCS and later on treaties with or without 40 Gy of gamma irradiation. The males were then subjected to the technical Cy L / Pm for the detection of recessive lethals. In the third generation the respective counts of the descendant of each one of them to determine the corresponding categories for each extracted chromosome were made. To be mendelian crosses it is expected for a normal chromosome a proportion 2:1 of individuals with genotype Cy L / +: +/+. The absence of individuals +/+ it is indicative of a lethal gene, until 10% of these individuals of each male's total descendant, it is considered that is carrying of a semi lethal gene. The sum of lethal and semi lethals constitutes the category detrimental. The obtained results indicated that the pre-treatment with CCS reduces in a significant way the frequency of induced lethals by 40 Gy of gamma rays. The fact that an effect inhibitor has not been observed in the test of recessive lethal bound to the sex obtained previously, it contrasts with the effect observed in the chromosome II, results of this study and with the one observed in the chromosome III in somatic cells. The above-mentioned shows a differential action of the CCS between sexual chromosomes and autosomal before the effect of the gamma radiation. At the moment we don't have an explanation to these evidences. To evaluate the action of the chlorophyllin on

Lethal body concentrations and accumulation patterns determine time-dependent toxicity of cadmium in soil arthropods

Energy Technology Data Exchange (ETDEWEB)

Crommentuijn, T.; Doodeman, C.J.A.M.; Doornekamp, A.; Pol, J.J.C. van der; Bedaux, J.J.M.; Gestel, C.A.M. van (Vrije Univ., Amsterdam (Netherlands))

1994-11-01

Time-dependent toxicity in bioassays is usually explained in terms of uptake and elimination kinetics of the toxicant. By comparing different species with essentially different accumulation kinetics, a firm test of this concept may be made. This article compares the sensitivity of six soil arthropods, the collembolans Orchesella cincta and Tomocerus minor, the oribatid mite Platynothrus peltifer, the isopods Porcellio scaber and Oniscus asellus, and the diplopod Cylindroiulus britannicus, when exposed to cadmium in the food. Survival was determined at various time intervals; accumulation of cadmium in the animals was measured at one time interval. Kinetic-based toxicity models were fitted to the data, and estimates were obtained for lethal body concentration, uptake rate constant, elimination rate constant, and ultimate LC50. Two different accumulation patterns could be discerned; these were correlated with time-survival relationships. One, species that have the possibility to eliminate cadmium will reach an equilibrium for the internal concentration and also an ultimate LC50. Two, species that are unable to eliminate cadmium but store it in the body will have an ultimate LC50 equal to zero. For these species the time in which the lethal body concentration is reached is more important. Taxonomically related species appeared to have comparable accumulation patterns, but lethal body concentrations differed. It is concluded that knowledge of the accumulation pattern is indispensable for the evaluation of species' sensitivities to toxicants.

Revertant mutation releases confined lethal mutation, opening Pandora's box: a novel genetic pathogenesis.

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Yasushi Ogawa

2014-05-01

Full Text Available When two mutations, one dominant pathogenic and the other "confining" nonsense, coexist in the same allele, theoretically, reversion of the latter may elicit a disease, like the opening of Pandora's box. However, cases of this hypothetical pathogenic mechanism have never been reported. We describe a lethal form of keratitis-ichthyosis-deafness (KID syndrome caused by the reversion of the GJB2 nonsense mutation p.Tyr136X that would otherwise have confined the effect of another dominant lethal mutation, p.Gly45Glu, in the same allele. The patient's mother had the identical misssense mutation which was confined by the nonsense mutation. The biological relationship between the parents and the child was confirmed by genotyping of 15 short tandem repeat loci. Haplotype analysis using 40 SNPs spanning the >39 kbp region surrounding the GJB2 gene and an extended SNP microarray analysis spanning 83,483 SNPs throughout chromosome 13 in the family showed that an allelic recombination event involving the maternal allele carrying the mutations generated the pathogenic allele unique to the patient, although the possibility of coincidental accumulation of spontaneous point mutations cannot be completely excluded. Previous reports and our mutation screening support that p.Gly45Glu is in complete linkage disequilibrium with p.Tyr136X in the Japanese population. Estimated from statisitics in the literature, there may be approximately 11,000 p.Gly45Glu carriers in the Japanese population who have this second-site confining mutation, which acts as natural genetic protection from the lethal disease. The reversion-triggered onset of the disesase shown in this study is a previously unreported genetic pathogenesis based on Mendelian inheritance.

Early events of lethal action by tobramycin in Pseudomonas aeruginosa

International Nuclear Information System (INIS)

Raulston, J.E.

1988-01-01

The immediate activities of the aminoglycoside antibiotic, tobramycin, were investigated in Pseudomonas aeruginosa PAO1. The influence of carbon growth substate and the antibiotic exposure environment in the magnitude of activity were examined. Lethality by 8 μg/ml tobramycin occurred rapidly (1 to 3 minutes). The release of specific cellular components into the supernatant was associated with lethality. This material was initially detected as an increase in UV-absorbance. Magnesium in the reaction mixture provided protection against lethality and leakage, but did not reverse lethal damage after a 3 minute tobramycin treatment. Also, uptake of 3 H-tobramycin was reduced in the presence of magnesium. Cells grown with glucose as a carbon source were more susceptible than organic acid grown cells as was the rapidity and amount of cell damage. Analyses of the leakage material revealed a 2-fold increase of protein in the supernatant after a 1-3 minute treatment which paralleled lethality. A prominent 29 kDa protein was observed by SDS-PAGE in the released material, which has been identified as the periplasmic enzyme, β-lactamase. The immediate activities of tobramycin did not involve (i) release of overall cell protein, (ii) massive loss of total pool amino acids, (iii) cell lysis, (iv) inhibition of proline uptake, (v) release of lipopolysaccharide, or (vi) leakage of ATP. Electron microscopy showed no apparent damage after a 3 minute exposure. 40% inhibition of protein synthesis had occurred by 3 minutes of exposure, while release of UV-absorbing material and lethality were detectable after only 1 minute. Resistant cystic fibrosis isolates of P. aeruginosa did not leak under the same experimental conditions, but one of two susceptible strains examined did show increased UV-absorbance following treatment

Reproductive-phase and interphase lethal cell damage after irradiation and treatment with cytostatics

International Nuclear Information System (INIS)

Hagemann, G.

1979-01-01

After X-ray irradiation of manual cells, two lethal fractions occur due to reproductive and interphase death under low and high radiation doses. The damage kinetics on which this fact is based is compared with hypothetical tumour frequencies and leucemia induction caused in experiments. The reproductive-lethal damage can be manifested by means of colony size spectrometry, with the median colony size class differences (MCD) serving as measure for the damage found. The simultaneous effects of the cytostatics BLEOMYCIN or ICRF 159 and X-rays on reproductive lethal and interphase-lethal damage are measured by means of MCD and survival fraction, and the additive and intensifying effect' is judged with the help of suitably defined terms. This shows that the clinically used ICRF 159 has an additive effect on interphase-lethal and a sub-additive effect on reproductive-lethal cell damage. Thus, favourable results may be expected for the electivity factor in fractionated irradiation and with regard to delayed damage in healthy tissue. (orig.) 891 MG/orig. 892 RDG [de

Effective lethal mutagenesis of influenza virus by three nucleoside analogs.

Science.gov (United States)

Pauly, Matthew D; Lauring, Adam S

2015-04-01

Lethal mutagenesis is a broad-spectrum antiviral strategy that exploits the high mutation rate and low mutational tolerance of many RNA viruses. This approach uses mutagenic drugs to increase viral mutation rates and burden viral populations with mutations that reduce the number of infectious progeny. We investigated the effectiveness of lethal mutagenesis as a strategy against influenza virus using three nucleoside analogs, ribavirin, 5-azacytidine, and 5-fluorouracil. All three drugs were active against a panel of seasonal H3N2 and laboratory-adapted H1N1 strains. We found that each drug increased the frequency of mutations in influenza virus populations and decreased the virus' specific infectivity, indicating a mutagenic mode of action. We were able to drive viral populations to extinction by passaging influenza virus in the presence of each drug, indicating that complete lethal mutagenesis of influenza virus populations can be achieved when a sufficient mutational burden is applied. Population-wide resistance to these mutagenic agents did not arise after serial passage of influenza virus populations in sublethal concentrations of drug. Sequencing of these drug-passaged viral populations revealed genome-wide accumulation of mutations at low frequency. The replicative capacity of drug-passaged populations was reduced at higher multiplicities of infection, suggesting the presence of defective interfering particles and a possible barrier to the evolution of resistance. Together, our data suggest that lethal mutagenesis may be a particularly effective therapeutic approach with a high genetic barrier to resistance for influenza virus. Influenza virus is an RNA virus that causes significant morbidity and mortality during annual epidemics. Novel therapies for RNA viruses are needed due to the ease with which these viruses evolve resistance to existing therapeutics. Lethal mutagenesis is a broad-spectrum strategy that exploits the high mutation rate and the low

Photoreactivable sector of lethal damage in ultraviolet-irradiated Escherichia coli cells

International Nuclear Information System (INIS)

Balgavy, P.

1976-01-01

The photoreactivable sector of lethal damage in Escherichia coli Bsub(s-1), Escherichia coli B/r Hcr - and Escherichia coli B/r Hcr + cells after ultraviolet irradiation at 254 nm is 0.823 +- 0.004, 0.70 +- 0.01 and 0.53 +- 0.06, respectively, at 99% confidence limits. For the low values of the photoreactivable sector in the B/r Hcr - and B/r Hcr + strains are likely to be responsible dark repair processes which eliminate lethal damage, brought about by pyrimidine dimers, preferably in comparison with lethal damage caused by photoproducts of another type. (author)

Heterochromatin position effects on circularized sex chromosomes cause filicidal embryonic lethality in Drosophila melanogaster.

Science.gov (United States)

Ferree, Patrick M; Gomez, Karina; Rominger, Peter; Howard, Dagnie; Kornfeld, Hannah; Barbash, Daniel A

2014-04-01

Some circularized X-Y chromosomes in Drosophila melanogaster are mitotically unstable and induce early embryonic lethality, but the genetic basis is unknown. Our experiments suggest that a large region of X-linked satellite DNA causes anaphase bridges and lethality when placed into a new heterochromatic environment within certain circularized X-Y chromosomes. These results reveal that repetitive sequences can be incompatible with one another in cis. The lethal phenotype also bears a remarkable resemblance to a case of interspecific hybrid lethality.

Stress response of the black coral Leiopathes glaberrima when exposed to sub-lethal amounts of crude oil and dispersant

Directory of Open Access Journals (Sweden)

Dannise V. Ruiz-Ramos

2017-12-01

Full Text Available The 2010 Deep Water Horizon oil well failure released billions of gallons of crude oil into the deep Gulf of Mexico, and, combined with chemical dispersants, this oil caused significant coral mortality. However, the mechanisms by which oil and dispersed oil impact deep marine fauna are not well understood. Here, we investigate the effects of oil and dispersed oil on a black coral common in the deep Gulf of Mexico, 'Leiopathes glaberrima. 'This coral occurs in several color morphs that show ecological and genetic differences. We hypothesized that dispersed oil would be more detrimental to coral health than oil alone and that this difference would be detectable in the gene expression response of the colonies even at sub-lethal concentrations. In two experiments, four and six colonies of red and white color morphs were exposed to oil, dispersant, and dispersed oil for a minimum of 96 hours. Visual assessment indicated that indeed dispersant and dispersed oil treatments were more damaging than oil alone, for target concentrations of 25 mg L–1. Decline in health was observed for all treatments, independently of color morphotype, but the decline was faster in the white colonies exposed to dispersant. The responses to the treatments were also investigated by monitoring gene expression after 24 hours of sub-lethal chemical exposure. Coral gene expression differed by chemical stressor. Interestingly, the polycyclic aromatic hydrocarbon biomarker gene, cytochrome P450, was only up-regulated in dispersed oil but not oil alone, suggesting that the dispersant increased the availability of such hydrocarbons in the tissue. The gene expression response was apparent at 24 hours when visual impacts were not (yet detectable. The use of chemical dispersants in oil-spill remediation may cause health declines in deep-water corals and deserves further study.

Sub-lethal effects of the neurotoxic pyrethroid insecticide Fastac 50EC on the general motor and locomotor activities of the non-targeted beneficial carabid beetle Platynus assimilis (Coleoptera: Carabidae).

Science.gov (United States)

Tooming, Ene; Merivee, Enno; Must, Anne; Sibul, Ivar; Williams, Ingrid

2014-06-01

Sub-lethal effects of pesticides on behavioural endpoints are poorly studied in carabids (Coleoptera: Carabidae) though changes in behaviour caused by chemical stress may affect populations of these non-targeted beneficial insects. General motor activity and locomotion are inherent in many behavioural patterns, and changes in these activities that result from xenobiotic influence mirror an integrated response of the insect to pesticides. Influence of pyrethroid insecticides over a wide range of sub-lethal doses on the motor activities of carabids still remains unclear. Video tracking of Platynus assimilis showed that brief exposure to alpha-cypermethrin at sub-lethal concentrations ranged from 0.01 to 100 mg L(-1) caused initial short-term (24 h) locomotor hypo-activity. In addition, significant short- and long-term concentration and time-dependent changes occurred in general motor activity patterns and rates. Conspicuous changes in motor activity of Platynus assimilis beetles treated at alpha-cypermethrin concentrations up to 75,000-fold lower than maximum field recommended concentration (MFRC) suggest that many, basic fitness-related behaviours might be severely injured as well. These changes may negatively affect carabid populations in agro-ecosystems. Long-term hypo-activity could directly contribute to decreased trap captures of carabids frequently observed after insecticide application in the field. © 2013 Society of Chemical Industry.

The bureaucratization of war: moral challenges exemplified by the covert lethal drone

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Richard Adams

2013-12-01

Full Text Available This article interrogates the bureaucratization of war, incarnate in the covert lethal drone. Bureaucracies are criticized typically for their complexity, inefficiency, and inflexibility. This article is concerned with their moral indifference. It explores killing, which is so highly administered, so morally remote, and of such scale, that we acknowledge a covert lethal program. This is a bureaucratized program of assassination in contravention of critical human rights. In this article, this program is seen to compromise the advance of global justice. Moreover, the bureaucratization of lethal force is seen to dissolve democratic ideals from within. The bureaucracy isolates the citizens from lethal force applied in their name. People are killed, in the name of the State, but without conspicuous justification, or judicial review, and without informed public debate. This article gives an account of the risk associated with the bureaucratization of the State's lethal power. Exemplified by the covert drone, this is power with formidable reach. It is power as well, which requires great moral sensitivity. Considering the drone program, this article identifies challenges, which will become more prominent and pressing, as technology advances.

Leaf gas exchange performance and the lethal water potential of five European species during drought.

Science.gov (United States)

Li, Shan; Feifel, Marion; Karimi, Zohreh; Schuldt, Bernhard; Choat, Brendan; Jansen, Steven

2016-02-01

Establishing physiological thresholds to drought-induced mortality in a range of plant species is crucial in understanding how plants respond to severe drought. Here, five common European tree species were selected (Acer campestre L., Acer pseudoplatanus L., Carpinus betulus L., Corylus avellana L. and Fraxinus excelsior L.) to study their hydraulic thresholds to mortality. Photosynthetic parameters during desiccation and the recovery of leaf gas exchange after rewatering were measured. Stem vulnerability curves and leaf pressure-volume curves were investigated to understand the hydraulic coordination of stem and leaf tissue traits. Stem and root samples from well-watered and severely drought-stressed plants of two species were observed using transmission electron microscopy to visualize mortality of cambial cells. The lethal water potential (ψlethal) correlated with stem P99 (i.e., the xylem water potential at 99% loss of hydraulic conductivity, PLC). However, several plants that were stressed beyond the water potential at 100% PLC showed complete recovery during the next spring, which suggests that the ψlethal values were underestimated. Moreover, we observed a 1 : 1 relationship between the xylem water potential at the onset of embolism and stomatal closure, confirming hydraulic coordination between leaf and stem tissues. Finally, ultrastructural changes in the cytoplasm of cambium tissue and mortality of cambial cells are proposed to provide an alternative approach to investigate the point of no return associated with plant death. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A quick method for testing recessive lethal damage with a diploid strain of Aspergillus nidulans

International Nuclear Information System (INIS)

Morpurgo, G.; Puppo, S.; Gualandi, G.; Conti, L.

1978-01-01

A simple method capable of detecting recessive lethal damage in a diploid strain of Aspergillus nidulans is described. The method scores the recessive lethals on the 1st, the 3rd and the 5th chromosomes, which represent about 40% of the total map of A. nidulans. Two examples of induced lethals, with ultraviolet irradiation and methyl methanesulfonate are shown. The frequency of lethals may reach 36% of the total population with UV irradiation. (Auth.)

Lethal mutagenesis: targeting the mutator phenotype in cancer.

Science.gov (United States)

Fox, Edward J; Loeb, Lawrence A

2010-10-01

The evolution of cancer and RNA viruses share many similarities. Both exploit high levels of genotypic diversity to enable extensive phenotypic plasticity and thereby facilitate rapid adaptation. In order to accumulate large numbers of mutations, we have proposed that cancers express a mutator phenotype. Similar to cancer cells, many viral populations, by replicating their genomes with low fidelity, carry a substantial mutational load. As high levels of mutation are potentially deleterious, the viral mutation frequency is thresholded at a level below which viral populations equilibrate in a traditional mutation-selection balance, and above which the population is no longer viable, i.e., the population undergoes an error catastrophe. Because their mutation frequencies are fine-tuned just below this error threshold, viral populations are susceptible to further increases in mutational load and, recently this phenomenon has been exploited therapeutically by a concept that has been termed lethal mutagenesis. Here we review the application of lethal mutagenesis to the treatment of HIV and discuss how lethal mutagenesis may represent a novel therapeutic approach for the treatment of solid cancers. Copyright © 2010 Elsevier Ltd. All rights reserved.

A new lethal sclerosing bone dysplasia

International Nuclear Information System (INIS)

Kingston, H.M.; Freeman, J.S.; Hall, C.M.

1991-01-01

A neonate is described with a lethal sclerosing bone dysplasia associated with prenatal fractures and craniofacial abnormalities including microcephaly, exophthalmos, hypoplastic nose and mid-face, small jaw and nodular hyperplasia of the gums. Parental consanguinity suggests that an autosomal recessive mutation is the likely aetiology. (orig.)

Lethal toxicity of industrial chemicals to early life stages of Tilapia guineensis.

Science.gov (United States)

Ezemonye, L I N; Ogeleka, D F; Okieimen, F E

2008-08-30

The toxic effects of industrial chemicals on three early life stages of an economically important fish, Tilapia guineensis were investigated using the Organisation for Economic Cooperation and Development (OECD) # 203 recommended semi-static renewal bioassay. The assessment was necessary for the uncontrollable disposal of Neatex (liquid detergent) and Norust CR 486 (corrosion inhibitor) into the Niger Delta environment of Nigeria. The estimated 96-h LC(50) for 7-, 14- and 28-day-old fish in Norust CR 486 exposure was considered "more toxic" than Neatex in all life stages and was dependent on species age, exposure duration and environment. In the fresh water test, for Neatex and Norust CR 486 exposures for day 7, 14 and 28, the 96-h LC50 were 8.79, 17.10 and 82.42 mg/l and 5.55, 13.58 and 20.21 mg/l, respectively. In the brackish test, 15.42 and 46.52 mg/l, not determined (ND) and 7.35, 13.95 and 24.50mg/l were obtained. Differential toxicity was observed in the fresh and brackish water fish for the two chemicals and controls at pchemicals provides a rationale for regulatory surveillance and monitoring of both chemicals in the fragile Niger Delta environment.

New type of lethal short-limbed dwarfism

Energy Technology Data Exchange (ETDEWEB)

Nairn, E.R.; Chapman, S.

1989-05-01

Details are presented of a most unusual osteo-chondrodysplasia which presents with lethal neonatal short-limbed dwarfism, defective ossification and nodular calcification with cartilage. The features resemble one case previously described in the literature.

Quantitative aspects of repair of potentially lethal damage in mammalian cells

International Nuclear Information System (INIS)

Iliakis, G.; Pohlit, W.

1979-01-01

Stationary cultures of Ehrlich ascites tumour cells were irradiated with X-rays and then immediately or after a time interval tsub(rep) plated to measure the survival. The increase in survival observed after delayed plating was interpreted as repair of potentially lethal damage. A cybernetic model was used to analyse these data. Three states of damage were assumed for the cells. In state A the cells could grow to macrocolonies, in state B the cells suffered potentially lethal damage and could grow to macrocolonies only if they were allowed to repair the damage and in state C the cells were lethally damaged. A method of deriving the values of the parameters of the model from the experimental data was given. The dependence of the reaction rate constant of the repair potentially lethal damage on the dose D was used to derive a possible mechanism for the production of the shoulder in the dose effect curve. Finally this model was compared with other models of radiation action in living cells. (author)

Genetics Home Reference: Amish lethal microcephaly

Science.gov (United States)

... 1 in 500 newborns in the Old Order Amish population of Pennsylvania. It has not been found outside this population. Related Information What information about a genetic condition can statistics provide? Why are some genetic ... gene cause Amish lethal microcephaly . The SLC25A19 gene provides instructions for ...

Lethals induced by γ-radiation in drosophila somatic cells

International Nuclear Information System (INIS)

Ivanov, A.I.

1989-01-01

Exposure of 3-hour drosophila male embryos to γ-radiation during the topographic segregation of the germ anlage nuclei caused recessive sex-linked lethals in somatic cells only. The selectivity of the screening was determined by the ratio of mutation frequencies induced in embryos and adult males. Analysis of lethal mutations shows that a minimal rate of the divergence between germinal and somatic patterns of the cell development is observed in the embryogenesis, the 3d instar larva and prepupa, and maximal in the 1st and 2nd larva and pupa

Dominant lethal mutations in male mice fed γ-irradiated diet

International Nuclear Information System (INIS)

Chauhan, P.S.; Aravindakshan, M.; Aiyer, A.S.; Sundaram, K.

1975-01-01

Three groups of Swiss male mice were fed a stock ration of an unirradiated or irradiated (2.5 Mrad) test diet for 8 wk. After the feeding period, the males were mated with groups of untreated female mice for 4 consecutive weeks. The females were autopsied at mid-term pregnancy for evaluation of dominant lethal mutations. Numbers of dead implantations, including deciduomas and dead embryos, showed no significant differences among the different groups, thus producing no evidence of any induced post-implantation lethality in mice fed on irradiated diet. Similarly, there was no indication of preimplantation lethality, since implantation rates remained comparable among different groups. Consumption of irradiated diet did not affect the fertility of mice. Total pre- and post-implantation loss, as indicated by the numbers of live implantations remained comparable among all the groups of mice. (author)

The Relationship between Perceived Sleep Quality, Polysomnographic Measures and Depressive Symptoms in Chemically-Injured Veterans: A Pilot Study.

Science.gov (United States)

Moshkani Farahani, Davood; Tavallaie, Abbas; Vahedi, Ensieh; Rezaiemaram, Peyman; Naderi, Zohreh; Talaie, Akram

2014-07-01

Sleep complaints are common among Iranian chemically-injured veterans. The growing body of research has investigated (in) equalities between such subjective complaints and objective sleep records. Moreover, sleep complaints are associated with depressive symptoms. Depressive symptoms, also, have been frequently reported in chemically-injured veterans. Therefore, the purpose of this pilot study was to investigate the relationship between perceived sleep quality, polysomnographic measures and depressive symptoms in Iranian veterans with chemical injuries. In this pilot study, 35 Iranian veterans with chemical injuries complaining of a sleep problem were selected. Initially, participants were evaluated via all-night polysomnography, then, they completed the research questionnaires. Collected data were analyzed using Pearson correlation coefficients. Data analyses showed that there was no significant correlation between many of self-reposted variables and polysomnogaphic recordings, however, remarkable relationships were found between the Pittsburgh Sleep Quality Index and the Beck Depression Inventory scores. The findings indicated that sleep complaints of chemically-injured veterans are not equivalent to objective sleep disturbances, however, these complaints are largely associated with level of depression. This study emphasizes the important role of mood in sleep evaluation. Further, the findings suggest using a combination of both subjective and objective measures for accurate assessment of sleep quality in Iranian veterans with chemical injuries (i.e., multimethod approach).

Consortium for Osteogenesis Imperfecta Mutations in the Helical Domain of Type I Collagen: Regions Rich in Lethal Mutations Align With Collagen Binding Sites for Integrins and Proteoglycans

Science.gov (United States)

Marini, Joan C.; Forlino, Antonella; Cabral, Wayne A.; Barnes, Aileen M.; San Antonio, James D.; Milgrom, Sarah; Hyland, James C.; Körkkö, Jarmo; Prockop, Darwin J.; De Paepe, Anne; Coucke, Paul; Symoens, Sofie; Glorieux, Francis H.; Roughley, Peter J.; Lund, Alan M.; Kuurila-Svahn, Kaija; Hartikka, Heini; Cohn, Daniel H.; Krakow, Deborah; Mottes, Monica; Schwarze, Ulrike; Chen, Diana; Yang, Kathleen; Kuslich, Christine; Troendle, James; Dalgleish, Raymond; Byers, Peter H.

2014-01-01

Osteogenesis imperfecta (OI) is a generalized disorder of connective tissue characterized by fragile bones and easy susceptibility to fracture. Most cases of OI are caused by mutations in type I collagen. We have identified and assembled structural mutations in type I collagen genes (COL1A1 and COL1A2, encoding the proα1(I) and proα2(I) chains, respectively) that result in OI. Quantitative defects causing type I OI were not included. Of these 832 independent mutations, 682 result in substitution for glycine residues in the triple helical domain of the encoded protein and 150 alter splice sites. Distinct genotype–phenotype relationships emerge for each chain. One-third of the mutations that result in glycine substitutions in α1(I) are lethal, especially when the substituting residues are charged or have a branched side chain. Substitutions in the first 200 residues are nonlethal and have variable outcome thereafter, unrelated to folding or helix stability domains. Two exclusively lethal regions (helix positions 691–823 and 910–964) align with major ligand binding regions (MLBRs), suggesting crucial interactions of collagen monomers or fibrils with integrins, matrix metalloproteinases (MMPs), fibronectin, and cartilage oligomeric matrix protein (COMP). Mutations in COL1A2 are predominantly nonlethal (80%). Lethal substitutions are located in eight regularly spaced clusters along the chain, supporting a regional model. The lethal regions align with proteoglycan binding sites along the fibril, suggesting a role in fibril–matrix interactions. Recurrences at the same site in α2(I) are generally concordant for outcome, unlike α1(I). Splice site mutations comprise 20% of helical mutations identified in OI patients, and may lead to exon skipping, intron inclusion, or the activation of cryptic splice sites. Splice site mutations in COL1A1 are rarely lethal; they often lead to frameshifts and the mild type I phenotype. In α2(I), lethal exon skipping events are

Relative Risks for Lethal Prostate Cancer Based on Complete Family History of Prostate Cancer Death.

Science.gov (United States)

Albright, Frederick S; Stephenson, Robert A; Agarwal, Neeraj; Cannon-Albright, Lisa A

2017-01-01

There are few published familial relative risks (RR) for lethal prostate cancer. This study estimates RRs for lethal prostate cancer based on comprehensive family history data, with the goal of improving identification of those men at highest risk of dying from prostate cancer. We used a population-based genealogical resource linked to a statewide electronic SEER cancer registry and death certificates to estimate relative risks (RR) for death from prostate cancer based upon family history. Over 600,000 male probands were analyzed, representing a variety of family history constellations of lethal prostate cancer. RR estimates were based on the ratio of the observed to the expected number of lethal prostate cancer cases using internal rates. RRs for lethal prostate cancer based on the number of affected first-degree relatives (FDR) ranged from 2.49 (95% CI: 2.27, 2.73) for exactly 1 FDR to 5.30 (2.13, 10.93) for ≥3 affected FDRs. In an absence of affected FDRs, increased risk was also significant for increasing numbers of affected second-degree or third degree relatives. Equivalent risks were observed for similar maternal and paternal family history. This study provides population-based estimates of lethal prostate cancer risk based on lethal prostate cancer family history. Many family history constellations associated with two to greater than five times increased risk for lethal prostate cancer were identified. These lethal prostate cancer risk estimates hold potential for use in identification, screening, early diagnosis, and treatment of men at high risk for death from prostate cancer. Prostate77:41-48, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

BRINE SHRIMP LETHALITY TEST (BSLT DARI BERBAGAI FRAKSI EKSTRAK DAGING BUAH DAN KULIT BIJI MAHKOTA DEWA (Phaleria macrocarpa

Directory of Open Access Journals (Sweden)

Vivi Lisdawati

2012-10-01

Full Text Available Biological activity of a natural product involved in several certain characteristics will influence its pharmaceutical application. Secondary metabolites, considered as chemical compounds, are now thought to mediate plant defense mechanism by providing chemical barriers against animal and microbial predators. Brine Shrimp Lethality Test (BSLT method has been used as preliminary test for screening the activity of chemical compounds in n­ hexane, ethyl acetate, and methanol extracts from mesocarp and seeds of Phaleria macrocarpa, fam. Thymelaeaceae. BSLT method used shrimp larvas of Artemia salina L. to study the mortality effect that was caused by the sample extracts. All of crude extracts showed bioactivity with LC50 values from 0.16 to 11.83 µg/ml (baseline 1000 µg/ml. It means, at the concentration the crude extracts can cause 50% mortality of A. salina L. shrimp larvas, after 24 hours incubation. These results clearly indicate that crude extracts of P. macrocarpa showed high potential biological activity.

Indirect effects of non-lethal predation on bivalve activity and sediment reworking

NARCIS (Netherlands)

Maire, O.; Merchant, J.N.; Bulling, M.; Teal, L.R.; Gremare, A.; Duchene, J.C.; Solan, M.

2010-01-01

Deposit-feeders are the dominant bioturbators of aquatic sediments, where they profoundly impact biogeochemical processes, but they are also vulnerable to both lethal and non-lethal predation by a large variety of predators. In this study, we performed a series of experiments to test the effects of

Sonographic features of lethal multiple pterygium syndrome at 14 weeks.

Science.gov (United States)

Chen, Min; Chan, Gavin Shueng Wai; Lee, Chin Peng; Tang, Mary Hoi Yin

2005-06-01

Lethal multiple pterygium syndrome is a rare inherited disorder. Previous reports suggest that the diagnosis may be based on prenatal sonographic demonstration of severe limb flexion, absence of fetal motion, and a large cystic hygroma in the second and third trimesters. We present the sonographic features and postmortem features of a fetus with lethal multiple pterygium syndrome at 13 weeks of gestation, which shows that the condition can possibly be diagnosed in the first trimester of pregnancy.

Influence of temperature and pressure on the lethality of ultrasound

International Nuclear Information System (INIS)

Raso, J.; Pagan, R.; Condon, S.; Sala, F.J.

1998-01-01

A specially designed resistometer was constructed, and the lethal effect on Yersinia enterocolitica of ultrasonic waves (UW) at different static pressures (manosonication [MS]) and of combined heat-UW under pressure treatments (manothermosonication [MTS]) was investigated. During MS treatments at 30 degrees C and 200 kPa, the increase in the amplitude of UW of 20 kHz from 21 to 150 micrometers exponentially decreased decimal reduction time values (D(MS)) from 4 to 0.37 min. When pressure was increased from 0 to 600 kPa at a constant amplitude (150 micrometers) and temperature (30 degrees C), D(MS) values decreased from 1.52 to 0.20 min. The magnitude of this decrease in D(MS) declined progressively as pressure was increased. The influence of pressure on D(MS) values was greater with increased amplitude of UW. Pressure alone of as much as 600 kPa did not influence the heat resistance of Y. enterocolitica (D60 = 0.094; zeta = 5.65). At temperatures of as much as 58 degrees C, the lethality of UW under pressure was greater than that of heat treatment alone at the same temperature. At higher temperatures, this difference disappeared. Heat and UW under pressure seemed to act independently. The lethality of MTS treatments appeared to result from the added effects of UW under pressure and the lethal effect of heat. The individual contributions of heat and of UW under pressure to the total lethal effect of MTS depended on temperature. The inactivating effect of UW was not due to titanium particles eroded from the sonication horn. The addition to the MS media of cysteamine did not increase the resistance of Y. enterocolitica to MS treatment. MS treatment caused cell disruption

Annotating novel genes by integrating synthetic lethals and genomic information

Directory of Open Access Journals (Sweden)

Faty Mahamadou

2008-01-01

Full Text Available Abstract Background Large scale screening for synthetic lethality serves as a common tool in yeast genetics to systematically search for genes that play a role in specific biological processes. Often the amounts of data resulting from a single large scale screen far exceed the capacities of experimental characterization of every identified target. Thus, there is need for computational tools that select promising candidate genes in order to reduce the number of follow-up experiments to a manageable size. Results We analyze synthetic lethality data for arp1 and jnm1, two spindle migration genes, in order to identify novel members in this process. To this end, we use an unsupervised statistical method that integrates additional information from biological data sources, such as gene expression, phenotypic profiling, RNA degradation and sequence similarity. Different from existing methods that require large amounts of synthetic lethal data, our method merely relies on synthetic lethality information from two single screens. Using a Multivariate Gaussian Mixture Model, we determine the best subset of features that assign the target genes to two groups. The approach identifies a small group of genes as candidates involved in spindle migration. Experimental testing confirms the majority of our candidates and we present she1 (YBL031W as a novel gene involved in spindle migration. We applied the statistical methodology also to TOR2 signaling as another example. Conclusion We demonstrate the general use of Multivariate Gaussian Mixture Modeling for selecting candidate genes for experimental characterization from synthetic lethality data sets. For the given example, integration of different data sources contributes to the identification of genetic interaction partners of arp1 and jnm1 that play a role in the same biological process.

Modeling response of species to microcontaminants: comparative ecotoxicology by (sub)lethal body burdens as a function of species size and partition ratio of chemicals.

Science.gov (United States)

Hendriks, A J

1995-11-01

A model was designed and calibrated with accumulation data to calculate the internal concentrations of microcontaminants in organisms as a function of a few constants and variables. The main factors are the exposure time, the external exposure concentration, the partition ratio of the compound, and the size of the taxon concerned. The model was applied to calculate the lethal and sublethal body burdens of several priority compounds and some major taxa. Estimations were generally confirmed at the order of magnitude level by measured residues and applied doses if available. According to the estimations, most priority compounds chosen were critical for most taxa above internal concentrations of 0.1 mmol.kg-1 wet wt. Trichloromethane, 1,2,4-trichlorobenzene, and hexachlorobenzene were lethal above this level only, whereas other organic microcontaminants affected at least some taxa at lower body burdens. The log(Kow) of the organic compounds ranged from 2.0 to 7.0. Keeping in mind that bioconcentration and -magnification ratios for metals may be quite variable, the lowest critical residues estimated were just below the value of 0.1 mmol.kg-1 wet wt. Here, external concentrations encountered in natural habitats seem to be a promising tool for predictive comparative ecotoxicology. The critical body burdens for plants and invertebrates may have been overestimated due to uncertainty about the parameters. Among the different taxa, however, the fish families chosen (Salmonidae and Cyprinidae) seem to be most sensitive to most compounds. Internal response concentrations of the herbicide atrazine were the lowest in micro- and macrophytes, whereas parathion affected invertebrates at low levels. The database that provided the external response concentrations was also consulted to estimate so-called extrapolation or safety factors. On average, long-term no effect concentrations in water are estimated to be about 10-30 times below short-term median lethal levels. In general, short

Clostridium sordellii lethal toxin kills mice by inducing a major increase in lung vascular permeability.

Science.gov (United States)

Geny, Blandine; Khun, Huot; Fitting, Catherine; Zarantonelli, Leticia; Mazuet, Christelle; Cayet, Nadège; Szatanik, Marek; Prevost, Marie-Christine; Cavaillon, Jean-Marc; Huerre, Michel; Popoff, Michel R

2007-03-01

When intraperitoneally injected into Swiss mice, Clostridium sordellii lethal toxin reproduces the fatal toxic shock syndrome observed in humans and animals after natural infection. This animal model was used to study the mechanism of lethal toxin-induced death. Histopathological and biochemical analyses identified lung and heart as preferential organs targeted by lethal toxin. Massive extravasation of blood fluid in the thoracic cage, resulting from an increase in lung vascular permeability, generated profound modifications such as animal dehydration, increase in hematocrit, hypoxia, and finally, cardiorespiratory failure. Vascular permeability increase induced by lethal toxin resulted from modifications of lung endothelial cells as evidenced by electron microscopy. Immunohistochemical analysis demonstrated that VE-cadherin, a protein participating in intercellular adherens junctions, was redistributed from membrane to cytosol in lung endothelial cells. No major sign of lethal toxin-induced inflammation was observed that could participate in the toxic shock syndrome. The main effect of the lethal toxin is the glucosylation-dependent inactivation of small GTPases, in particular Rac, which is involved in actin polymerization occurring in vivo in lungs leading to E-cadherin junction destabilization. We conclude that the cells most susceptible to lethal toxin are lung vascular endothelial cells, the adherens junctions of which were altered after intoxication.

Evaluating the Predictive Validity of Suicidal Intent and Medical Lethality in Youth

Science.gov (United States)

Sapyta, Jeffrey; Goldston, David B.; Erkanli, Alaattin; Daniel, Stephanie S.; Heilbron, Nicole; Mayfield, Andrew; Treadway, S. Lyn

2012-01-01

Objectives: To examine whether suicidal intent and medical lethality of past suicide attempts are predictive of future attempts, the association between intent and lethality, and the consistency of these characteristics across repeated attempts among youth. Method: Suicide attempts in a 15-year prospective study of 180 formerly psychiatrically…

`Human nature': Chemical engineering students' ideas about human relationships with the natural world

Science.gov (United States)

Goldman, Daphne; Ben-Zvi Assaraf, Orit; Shemesh, Julia

2014-05-01

While importance of environmental ethics, as a component of sustainable development, in preparing engineers is widely acknowledged, little research has addressed chemical engineers' environmental concerns. This study aimed to address this void by exploring chemical engineering students' values regarding human-nature relationships. The study was conducted with 247 3rd-4th year chemical engineering students in Israeli Universities. It employed the New Ecological Paradigm (NEP)-questionnaire to which students added written explanations. Quantitative analysis of NEP-scale results shows that the students demonstrated moderately ecocentric orientation. Explanations to the NEP-items reveal diverse, ambivalent ideas regarding the notions embodied in the NEP, strong scientific orientation and reliance on technology for addressing environmental challenges. Endorsing sustainability implies that today's engineers be equipped with an ecological perspective. The capacity of Higher Education to enable engineers to develop dispositions about human-nature interrelationships requires adaptation of curricula towards multidisciplinary, integrative learning addressing social-political-economic-ethical perspectives, and implementing critical-thinking within the socio-scientific issues pedagogical approach.

Identification of Lilial as a fragrance sensitizer in a perfume by bioassay-guided chemical fractionation and structure-activity relationships.

Science.gov (United States)

Arnau, E G; Andersen, K E; Bruze, M; Frosch, P J; Johansen, J D; Menné, T; Rastogi, S C; White, I R; Lepoittevin, J P

2000-12-01

Fragrance materials are among the most common causes of allergic contact dermatitis. The aim of this study was to identify in a perfume fragrance allergens not included in the fragrance mix, by use of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships (SARs). The basis for the investigation was a 45-year-old woman allergic to her own perfume. She had a negative patch test to the fragrance mix and agreed to participate in the study. Chemical fractionation of the perfume concentrate was used for repeated patch testing and/or repeated open application test on the pre-sensitized patient. The chemical composition of the fractions giving a positive patch-test response and repeated open application test reactions was obtained by gas chromatography-mass spectrometry. From the compounds identified, those that contained a "structural alert" in their chemical structure, indicating an ability to modify skin proteins and thus behave as a skin sensitizer, were tested on the patient. The patient reacted positively to the synthetic fragrance p-t-butyl-alpha-methylhydrocinnamic aldehyde (Lilial), a widely used fragrance compound not present in the fragrance mix. The combination of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships seems to be a valuable tool for the investigation of contact allergy to fragrance materials.

Straightening Beta: Overdispersion of Lethal Chromosome Aberrations following Radiotherapeutic Doses Leads to Terminal Linearity in the Alpha–Beta Model

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Igor Shuryak

2017-12-01

Full Text Available Recent technological advances allow precise radiation delivery to tumor targets. As opposed to more conventional radiotherapy—where multiple small fractions are given—in some cases, the preferred course of treatment may involve only a few (or even one large dose(s per fraction. Under these conditions, the choice of appropriate radiobiological model complicates the tasks of predicting radiotherapy outcomes and designing new treatment regimens. The most commonly used model for this purpose is the venerable linear-quadratic (LQ formalism as it applies to cell survival. However, predictions based on the LQ model are frequently at odds with data following very high acute doses. In particular, although the LQ predicts a continuously bending dose–response relationship for the logarithm of cell survival, empirical evidence over the high-dose region suggests that the survival response is instead log-linear with dose. Here, we show that the distribution of lethal chromosomal lesions among individual human cells (lymphocytes and fibroblasts exposed to gamma rays and X rays is somewhat overdispersed, compared with the Poisson distribution. Further, we show that such overdispersion affects the predicted dose response for cell survival (the fraction of cells with zero lethal lesions. This causes the dose response to approximate log-linear behavior at high doses, even when the mean number of lethal lesions per cell is well fitted by the continuously curving LQ model. Accounting for overdispersion of lethal lesions provides a novel, mechanistically based explanation for the observed shapes of cell survival dose responses that, in principle, may offer a tractable and clinically useful approach for modeling the effects of high doses per fraction.

Differential expression of the lethal gene Luteus-Pa in cacao of the Parinari series.

Science.gov (United States)

Rehem, B C; Almeida, A-A F; Figueiredo, G S F; Gesteira, A S; Santos, S C; Corrêa, R X; Yamada, M M; Valle, R R

2016-02-22

The recessive lethal character Luteus-Pa is found in cacao (Theobroma cacao) genotypes of the Parinari series (Pa) and is characterized by expression of leaf chlorosis and seedling death. Several genotypes of the Pa series are bearers of the gene responsible for the expression of the Luteus-Pa character, which can be used as a tool for determining relationships between genotypes of this group. To evaluate this phenomenon, we analyzed the differential expression of genes between mutant seedlings and wild-type hybrid Pa 30 x 169 seedlings, with the aim of elucidating the possible lethal mechanisms of the homozygous recessive character Luteus-Pa. Plant material was harvested from leaves of wild and mutant seedlings at different periods to construct a subtractive library and perform quantitative analysis using real-time PCR. The 649 sequences obtained from the subtractive library had an average length of 500 bp, forming 409 contigs. The probable proteins encoded were grouped into 10 functional categories. Data from ESTs identified genes associated with Rubisco, peroxidases, and other proteins and enzymes related to carbon assimilation, respiration, and photosystem 2. Mutant seedlings were characterized by synthesizing defective PsbO and PsbA proteins, which were overexpressed from 15 to 20 days after seedling emergence.

Public Laws Authorization and Appropriations Acts 1969-2007 for the U.S. Army Chemical Materials Agency

Science.gov (United States)

2006-11-06

agents, chemical herbicides , smoke and other obscuration materials. (2) The term "lethal chemical agent and munition" means a chemical agent or...military purposes and harmless to human beings under normal circumstances. (k) EFFECTIVE DATE -- The provisions of this section shall take effect on...the ecological and physiological dangers inherent in the use of herbicides , and (B) the 117 ecological and Physiological effects of the defoliation

The Effects of Anthrax Lethal Toxin on Host Barrier Function

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David M. Frucht

2011-06-01

Full Text Available The pathological actions of anthrax toxin require the activities of its edema factor (EF and lethal factor (LF enzyme components, which gain intracellular access via its receptor-binding component, protective antigen (PA. LF is a metalloproteinase with specificity for selected mitogen-activated protein kinase kinases (MKKs, but its activity is not directly lethal to many types of primary and transformed cells in vitro. Nevertheless, in vivo treatment of several animal species with the combination of LF and PA (termed lethal toxin or LT leads to morbidity and mortality, suggesting that LT-dependent toxicity is mediated by cellular interactions between host cells. Decades of research have revealed that a central hallmark of this toxicity is the disruption of key cellular barriers required to maintain homeostasis. This review will focus on the current understanding of the effects of LT on barrier function, highlighting recent progress in establishing the molecular mechanisms underlying these effects.

Analysis of time of death of prenatally lethal Steeloid mutations

International Nuclear Information System (INIS)

Rinchik, E.M.; Cummings, C.C.; Bangham, J.W.; Hunsicker, P.R.; Phipps, E.L.; Stelzner, K.F.

1987-01-01

Deletion mutations have been extremely useful in initiating the functional and molecular dissections of regions of the mouse genome. For the d-se and c regions, for example, it was observed that radiation mutations carrying lethal factors separable, by complementation analysis, from the primary d, se, or c mutation itself, could often be associated at both the genetic and molecular levels with multilocus chromosomal deletions. Since many of the Oak Ridge Sld mutations arose in radiation mutagenesis experiments, a substantial number may carry chromosomal deletions that involve the Sl locus in chromosome 10. Because of the great value of deletion mutations for the genetic and molecular analysis of chromosomal regions and complex genetic loci, they have initiated a series of experiments designed to test whether radiation-induced Sld mutations carry other lethal factors, in addition to the lethality caused by severe alleles of the Sl locus itself, as one prescreen for identifying Sld's that are caused by deletions

The evolution of lethal intergroup violence

OpenAIRE

Kelly, Raymond C.

2005-01-01

Recent findings and analyses in evolutionary biology, archaeology, and ethnology provide a favorable conjuncture for examining the evolution of lethal intergroup violence among hominids during the 2.9-million-year Paleolithic time span. Here, I seek to identify and investigate the main turning points in this evolutionary trajectory and to delineate the periodization that follows from this inquiry.

The evolution of lethal intergroup violence.

Science.gov (United States)

Kelly, Raymond C

2005-10-25

Recent findings and analyses in evolutionary biology, archaeology, and ethnology provide a favorable conjuncture for examining the evolution of lethal intergroup violence among hominids during the 2.9-million-year Paleolithic time span. Here, I seek to identify and investigate the main turning points in this evolutionary trajectory and to delineate the periodization that follows from this inquiry.

77 FR 6548 - Notice of Availability of Ballistic Survivability, Lethality and Vulnerability Analyses

Science.gov (United States)

2012-02-08

... DEPARTMENT OF DEFENSE Department of the Army Notice of Availability of Ballistic Survivability, Lethality and Vulnerability Analyses AGENCY: Department of the Army, DoD. ACTION: Notice of availability. SUMMARY: The US Army Research Laboratory's (ARL's), Survivability, Lethality Analysis Directorate (SLAD...

The Relationship between Perceived Sleep Quality, Polysomnographic Measures and Depressive Symptoms in Chemically-Injured Veterans: A Pilot Study.

Directory of Open Access Journals (Sweden)

Davood Moshkani Farahani

2014-09-01

Full Text Available Sleep complaints are common among Iranian chemically-injured veterans. The growing body of research has investigated (in equalities between such subjective complaints and objective sleep records. Moreover, sleep complaints are associated with depressive symptoms. Depressive symptoms, also, have been frequently reported in chemically-injured veterans. Therefore, the purpose of this pilot study was to investigate the relationship between perceived sleep quality, polysomnographic measures and depressive symptoms in Iranian veterans with chemical injuries.In this pilot study, 35 Iranian veterans with chemical injuries complaining of a sleep problem were selected. Initially, participants were evaluated via all-night polysomnography, then, they completed the research questionnaires. Collected data were analyzed using Pearson correlation coefficients.Data analyses showed that there was no significant correlation between many of self-reposted variables and polysomnogaphic recordings, however, remarkable relationships were found between the Pittsburgh Sleep Quality Index and the Beck Depression Inventory scores.The findings indicated that sleep complaints of chemically-injured veterans are not equivalent to objective sleep disturbances, however, these complaints are largely associated with level of depression. This study emphasizes the important role of mood in sleep evaluation. Further, the findings suggest using a combination of both subjective and objective measures for accurate assessment of sleep quality in Iranian veterans with chemical injuries (i.e., multimethod approach.

Exploring sets of molecules from patents and relationships to other active compounds in chemical space networks

Science.gov (United States)

Kunimoto, Ryo; Bajorath, Jürgen

2017-09-01

Patents from medicinal chemistry represent a rich source of novel compounds and activity data that appear only infrequently in the scientific literature. Moreover, patent information provides a primary focal point for drug discovery. Accordingly, text mining and image extraction approaches have become hot topics in patent analysis and repositories of patent data are being established. In this work, we have generated network representations using alternative similarity measures to systematically compare molecules from patents with other bioactive compounds, visualize similarity relationships, explore the chemical neighbourhood of patent molecules, and identify closely related compounds with different activities. The design of network representations that combine patent molecules and other bioactive compounds and view patent information in the context of current bioactive chemical space aids in the analysis of patents and further extends the use of molecular networks to explore structure-activity relationships.

Lethal Zika Virus Disease Models in Young and Older Interferon α/β Receptor Knock Out Mice

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Andrea Marzi

2018-04-01

Full Text Available The common small animal disease models for Zika virus (ZIKV are mice lacking the interferon responses, but infection of interferon receptor α/β knock out (IFNAR−/− mice is not uniformly lethal particularly in older animals. Here we sought to advance this model in regard to lethality for future countermeasure efficacy testing against more recent ZIKV strains from the Asian lineage, preferably the American sublineage. We first infected IFNAR−/− mice subcutaneously with the contemporary ZIKV-Paraiba strain resulting in predominantly neurological disease with ~50% lethality. Infection with ZIKV-Paraiba by different routes established a uniformly lethal model only in young mice (4-week old upon intraperitoneal infection. However, intraperitoneal inoculation of ZIKV-French Polynesia resulted in uniform lethality in older IFNAR−/− mice (10–12-weeks old. In conclusion, we have established uniformly lethal mouse disease models for efficacy testing of antivirals and vaccines against recent ZIKV strains representing the Asian lineage.

Lethal action of soluble metallic salts on fishes

Energy Technology Data Exchange (ETDEWEB)

Carpenter, K E

1927-01-01

A study of pollution of Welsh rivers by lead-mine effluents revealed the fact that fishes were killed by the action of soluble salts of lead, which proved lethal at concentrations so low as pb i : 3,000,000. A physiological investigation of the action of lead-salts revealed the following facts: the action does not correspond to the normal toxic type. The graph of survival-times in different concentrations closely follows the equation: K = i/t log i/conc. The speed of the reaction is dependent upon the total quantity of metallic ion present, as well as upon the actual concentrations. The speed of the reaction varies in inverse relation to the size and weight of fishes employed. The most marked symptom is the formation of a film over gills and skin, by interaction of the metallic ion with a mucus-constituent. Death by suffocation is the final result. Where insufficient lead ion is present, the film is shed off, and complete recovery takes place. The speed of the reaction varies in direct relation to the temperature. Chemical analysis of residues shows that no trace of metallic ion penetrates into the body itself. The action is thus held to be purely external in process, chemical in type, and mechanical in effect; i.e., it is not a toxic action in the ordinary sense of the term. The action of soluble salts of zinc, iron, copper, cadmium, and mercury is shown to follow the same law as that of lead. Attention is directed to the economic importance of the facts, in connection with the pollution of rivers.

RBE-LET relationships for different types of lethal radiation damage in mammalian cells: comparison with DNA dsb and an interpretation of differences in radiosensitivity

NARCIS (Netherlands)

Barendsen, G. W.

1994-01-01

Relative biological effectiveness (RBE), as a function of linear energy transfer (LET), is evaluated for different types of damage contributing to mammalian cell reproductive death. Survival curves are analysed assuming a linear-quadratic dose dependence of lethal lesions. The linear term represents

Effect of ionizing radiation on chemical and biological properties of Salmonella minnesota R595 lipopolysaccharide

Energy Technology Data Exchange (ETDEWEB)

El Sabbagh, M; Galanos, C; Luederitz, O [Max-Planck-Institut fuer Immunbiologie, Freiburg (Germany, F.R.); Bertok, L [Orszagos Frederic Joliot-Curie Sugarbiologiai es Sugaregeszseguegyi Kutato Intezet, Budapest (Hungary); Fuest, Gy [Orszagos Haema--tologiai es Vertranszfuzios Intezet, Budapest (Hungary)

1982-01-01

The effects of /sup 60/Co irradiation performed with various doses on the biological and chemical properties of the endotoxin of the Salmonella minnesota R595 were compared with those of unirradiated ones. The biological activity was measured using the lethal toxicity test, the local Schwartzman reaction and by activating the complementary system. Increasing the irradiation dose from 50 to 200 kGy the preparation became less active in the biological tests but the protective activity against the lethal action of the endotoxin remained uneffected. The irradiation resulted in a dose-dependent decrease of the amounts of 2-keto-3-deoxy-octonate, glucosamine, fatty acids, but did not affect all the degradation products identified. Therefore, no correlation between the chemical composition and the absence of endotoxin activity was found.

Damage to E. coli cells induced by tritium decay: secondary lethality under nongrowth conditions

International Nuclear Information System (INIS)

Koukalova, B.; Kuhrova, V.

1980-01-01

Cells containing incorporated 3 H-thymidine are damaged by its decay. It was found with E.coli TAU-bar cells that a small part of the damage is lethal whereas most of it is reparable and only potentially lethal. If cells are subjected to nongrowth conditions, the potentially lethal damage changes to lethal damage. This process is called secondary lethality (SL). The extent of SL and some changes in DNA under three different modes of growth inhibition were determined. It was found that: (i) SL is maximal under conditions of amino acid starvation (-AA), the viable count decreasing by two orders of magnitude. (ii) SL is 4 times lower in the presence of chloramphenicol (-AA+CLP) and 6.5 times lower under +AA+CLP conditions. Changes in the sedimentation rate of DNA determined in alkaline sucrose gradient correlate with the differences in SL: under -AA conditions the sedimentation rate of DNA decreases whereas in the presence of CLP no decrease occurs. The results suggest that certain enzymatic processes take place under -AA conditions which lead to irreparable changes in DNA. (author)

Damage to E. coli cells induced by tritium decay: secondary lethality under nongrowth conditions

Energy Technology Data Exchange (ETDEWEB)

Koukalova, B; Kuhrova, V [Ceskoslovenska Akademie Ved, Brno. Biofysikalni Ustav

1980-05-01

Cells containing incorporated /sup 3/H-thymidine are damaged by its decay. It was found with E.coli TAU-bar cells that a small part of the damage is lethal whereas most of it is reparable and only potentially lethal. If cells are subjected to nongrowth conditions, the potentially lethal damage changes to lethal damage. This process is called secondary lethality (SL). The extent of SL and some changes in DNA under three different modes of growth inhibition were determined. It was found that: (i) SL is maximal under conditions of amino acid starvation (-AA), the viable count decreasing by two orders of magnitude. (ii) SL is 4 times lower in the presence of chloramphenicol (-AA+CLP) and 6.5 times lower under +AA+CLP conditions. Changes in the sedimentation rate of DNA determined in alkaline sucrose gradient correlate with the differences in SL: under -AA conditions the sedimentation rate of DNA decreases whereas in the presence of CLP no decrease occurs. The results suggest that certain enzymatic processes take place under -AA conditions which lead to irreparable changes in DNA.

Modeling Chemical Interaction Profiles: I. Spectral Data-Activity Relationship and Structure-Activity Relationship Models for Inhibitors and Non-inhibitors of Cytochrome P450 CYP3A4 and CYP2D6 Isozymes

OpenAIRE

McPhail, Brooks; Tie, Yunfeng; Hong, Huixiao; Pearce, Bruce A.; Schnackenberg, Laura K.; Ge, Weigong; Valerio, Luis G.; Fuscoe, James C.; Tong, Weida; Buzatu, Dan A.; Wilkes, Jon G.; Fowler, Bruce A.; Demchuk, Eugene; Beger, Richard D.

2012-01-01

An interagency collaboration was established to model chemical interactions that may cause adverse health effects when an exposure to a mixture of chemicals occurs. Many of these chemicals—drugs, pesticides, and environmental pollutants—interact at the level of metabolic biotransformations mediated by cytochrome P450 (CYP) enzymes. In the present work, spectral data-activity relationship (SDAR) and structure-activity relationship (SAR) approaches were used to develop machine-learning classifi...

Efficiency of interaction between various radiation and chemicals

International Nuclear Information System (INIS)

Kim, Jin Kyu; Song, H. S.; Kim, J. S.; Chun, K. J.; Lee, Y. K.; Lee, B. H.; Shin, H. S.; Lee, K. H.; Petin, Vladislav G.

2002-01-01

KAERI and INP (Poland) have been carried out parallel study and joint experiments on the major topics according to MOU about their cooperative project. Major experimental techniques were TSH assay, comet assay, and synergism assay. The research consisted of the following workscopes. 1) Application of TSH bioindicator for studying the biological efficiency of radiation, 2) Relative biological efficiency of californium-252 neutrons in the induction of gene and lethal mutations in TSH cells normal and enriched with boron compound, 3) Effect of pesticide on radiation-induced mutations in TSH cells, 4) Interaction of radiation with pesticide on DNA damage in human peripheral blood lymphocytes, 5) Radiomodifying effect of boron and gadolinium compounds in human peripheral blood lymphocytes, 6) Mathematical description of synergistic interactions, 7) General regularities of synergistic interactions, and 8) Determinant of synergistic interaction between radiation, heat and chemicals in cell killing. Both institutes have established wide variety of research techniques applicable to various radiation research through the cooperation. The results of research can make the role of fundamental basis for the better relationship between Korea and Poland

Synthetic Lethal Therapeutic Approaches for ARID1A-Mutated Ovarian Cancer

Science.gov (United States)

2017-10-01

Award Number: W81XWH-16-1-0496 TITLE: Synthetic lethal therapeutic approaches for ARID1A-mutated ovarian cancer PRINCIPAL INVESTIGATOR: Rugang...AND SUBTITLE Synthetic lethal therapeutic approaches for ARID1A-mutated ovarian cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0496 5c...Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological

Exposure-dependent variation in cryolite induced lethality in the nontarget insect, Drosophila melanogaster

Directory of Open Access Journals (Sweden)

Podder Sayanti

2014-03-01

Full Text Available The starting point of toxicity testing of any chemical in an organism is the determination of its Lethal Concentration 50 (LC50. In the present study, LC50 of a fluorinated insecticide cryolite is determined in a non-target insect model, Drosophila melanogaster. Interestingly, the result shows that acute LC50 of cryolite was much greater in comparison to the chronic one in case of Drosophila larvae. Larvae which were exposed to 65,000 to 70,000 μg/ml cryolite through food showed 50% mortality after 18 hours of acute exposure, whereas only 150 to 160 μg/ml cryolite was sufficient to cause 50% mortality in case of chronic exposure. Thus cryolite in a small amount when applied once cannot produce noticeable changes in Drosophila, whereas the same amount when used continuously can be fatal. The non-feeding pupal stage was also seen to be affected by chemical treatment. This suggests that the test chemical affects the developmental fate and results in failure of adult emergence. Absence of chemical-induced mortality in adults assumes that the toxicity of cryolite might be restricted to the preimaginal stages of the organism. Reduction in body size of larvae after ingestion of cryolite (with food in acute treatment schedule is another interesting finding of this study. Some individuals consuming cryolite containing food cannot survive whereas the few survivors manifest a significant growth retardation which might be due to a tendency of refusal in feeding. Hence the present findings provide a scope of assessment of risk of other similar non-target groups

Differential response of human and rodent cell lines to chemical inhibition of the repair of potentially lethal damage

Energy Technology Data Exchange (ETDEWEB)

Little, J.B.; Ueno, A.M.; Dahlberg, W.K.

1989-07-01

We have examined the effects of several classes of metabolic inhibitors on the repair of potentially lethal damage in density-inhibited cultures of two rodent and two human cell systems which differ in their growth characteristics. Aphidicolin, 1-..beta..-D-arabinofuranosylcytosine (ara-C) and hydroxyurea showed no effect on PLD repair, whereas the effects of 9-..beta..-D-arabinofuranosyladenine (ara-A) and 3-aminobenzamide (3-AB) were cell line dependent. For example, 3-AB suppressed PLD repair almost completely in CHO cells, but showed no inhibitory effects in human diploid fibroblasts. These results indicate that inhibitors of DNA replication and poly(ADP-ribose) synthesis are not efficient inhibitors of cellular recovery in irradiated cells and, moreover, that such effects may be cell line dependent.

Lethal domestic violence in eastern North Carolina.

Science.gov (United States)

Gilliland, M G; Spence, P R; Spence, R L

2000-01-01

Strategies for preventing domestic violence can be tailored to a particular geographic or socioeconomic area if the patterns of domestic violence in the area are known. National statistics, although widely available, may not be applicable to a specific region. We reviewed homicide deaths in Eastern North Carolina between 1978 and 1999 to identify patterns in this rural area. Approximately 20% of the homicide deaths in eastern North Carolina are caused by intimate partners. Women accounted for 53% of the victims in 1976, similar to national figures but not rising to 72% as seen nationally in 1998. Latinos are an increasing presence in the area, but had only one recorded episode of lethal violence against an intimate partner. Gunshots accounted for most of the deaths (59% in men, 72% in women). Knowledge of such patterns can assist in selecting prevention strategies for this particular area. Over the last 25 years increasing attention has been devoted to domestic violence (DV), initially defined as abuse committed against a spouse, former spouse, fiancée, boy- or girlfriend, or cohabitant. As time has passed, the definition has been broadened to include other family members--elders, children, and siblings. The Centers for Disease Control and Prevention (CDC) now uses the term "intimate partner violence" for intentional emotional or physical abuse inflicted by a spouse, ex-spouse, a present or former boy- or girlfriend, or date. For the purposes of this paper, we consider DV interchangeable with intimate partner violence. There has been a national concern that abusive events are under-reported. The National Crime Victimization Survey, an anonymous household survey, indicated nearly 1 million incidents of non-lethal intimate partner violence per year between 1992 and 1996. The number decreased from 1.1 million in 1993 to 840,000 in 1996. Attempts to validate such data for a given geographic area often require subjects to violate anonymity--this may account for lower

Variability in mutational fitness effects prevents full lethal transitions in large quasispecies populations

Science.gov (United States)

Sardanyés, Josep; Simó, Carles; Martínez, Regina; Solé, Ricard V.; Elena, Santiago F.

2014-04-01

The distribution of mutational fitness effects (DMFE) is crucial to the evolutionary fate of quasispecies. In this article we analyze the effect of the DMFE on the dynamics of a large quasispecies by means of a phenotypic version of the classic Eigen's model that incorporates beneficial, neutral, deleterious, and lethal mutations. By parameterizing the model with available experimental data on the DMFE of Vesicular stomatitis virus (VSV) and Tobacco etch virus (TEV), we found that increasing mutation does not totally push the entire viral quasispecies towards deleterious or lethal regions of the phenotypic sequence space. The probability of finding regions in the parameter space of the general model that results in a quasispecies only composed by lethal phenotypes is extremely small at equilibrium and in transient times. The implications of our findings can be extended to other scenarios, such as lethal mutagenesis or genomically unstable cancer, where increased mutagenesis has been suggested as a potential therapy.

Electroshock weapons can be lethal!

Science.gov (United States)

Lundquist, Marjorie

2008-03-01

Electroshock weapons (EWs)-stun guns, tasers, riot shields-are electroconductive devices designed to safely incapacitate healthy men neuromuscularly, so they are called nonlethal or less-lethal. EW firms seeking large nonmilitary markets targeted law enforcement and corrections personnel, who began using EWs in prisons/jails and on public patrol in 1980 in the USA. This shifted the EW-shocked population from healthy soldiers to a heterogeneous mix of both sexes, ages 6-92, in a wide variety of health conditions! An EW operates by disrupting normal physiological processes, producing transient effects in healthy people. But if a person's health is sufficiently compromised, the margin of safety can be lost, resulting in death or permanent health problems. 325 people have died after EW shock since 1980. Did the EW cause these deaths? Evidence indicates that EWs do play a causal role in most such deaths. EWs can be lethal for people in diabetic shock^1 (hypoglycemia), which may be why Robert Dziekanski-a Polish immigrant to Canada-died so quickly after he was tasered at Vancouver Airport: not having eaten for over 10 hours, he likely was severely hypoglycemic. The EW death rate in North America is 30 times higher than need be, because EW users have not been properly trained to use EWs on a heterogeneous population safely! ^1J. Clinical Engineering 30(3):111(2005).

A new type of lethal short-limbed dwarfism

International Nuclear Information System (INIS)

Nairn, E.R.; Chapman, S.

1989-01-01

Details are presented of a most unusual osteo-chondrodysplasia which presents with lethal neonatal short-limbed dwarfism, defective ossification and nodular calcification with cartilage. The features resemble one case previously described in the literature. (orig.)

Overall view of chemical and biochemical weapons.

Science.gov (United States)

Pitschmann, Vladimír

2014-06-04

This article describes a brief history of chemical warfare, which culminated in the signing of the Chemical Weapons Convention. It describes the current level of chemical weapons and the risk of using them. Furthermore, some traditional technology for the development of chemical weapons, such as increasing toxicity, methods of overcoming chemical protection, research on natural toxins or the introduction of binary technology, has been described. In accordance with many parameters, chemical weapons based on traditional technologies have achieved the limit of their development. There is, however, a big potential of their further development based on the most recent knowledge of modern scientific and technical disciplines, particularly at the boundary of chemistry and biology. The risk is even higher due to the fact that already, today, there is a general acceptance of the development of non-lethal chemical weapons at a technologically higher level. In the future, the chemical arsenal will be based on the accumulation of important information from the fields of chemical, biological and toxin weapons. Data banks obtained in this way will be hardly accessible and the risk of their materialization will persist.

Overall View of Chemical and Biochemical Weapons

Directory of Open Access Journals (Sweden)

Vladimír Pitschmann

2014-06-01

Full Text Available This article describes a brief history of chemical warfare, which culminated in the signing of the Chemical Weapons Convention. It describes the current level of chemical weapons and the risk of using them. Furthermore, some traditional technology for the development of chemical weapons, such as increasing toxicity, methods of overcoming chemical protection, research on natural toxins or the introduction of binary technology, has been described. In accordance with many parameters, chemical weapons based on traditional technologies have achieved the limit of their development. There is, however, a big potential of their further development based on the most recent knowledge of modern scientific and technical disciplines, particularly at the boundary of chemistry and biology. The risk is even higher due to the fact that already, today, there is a general acceptance of the development of non-lethal chemical weapons at a technologically higher level. In the future, the chemical arsenal will be based on the accumulation of important information from the fields of chemical, biological and toxin weapons. Data banks obtained in this way will be hardly accessible and the risk of their materialization will persist.

The Relationship between Perceived Sleep Quality, Polysomnographic Measures and Depressive Symptoms in Chemically-Injured Veterans: A Pilot Study

OpenAIRE

Moshkani Farahani, Davood; Tavallaie, Abbas; Vahedi, Ensieh; Rezaiemaram, Peyman; Naderi, Zohreh; Talaie, Akram

2014-01-01

Objective Sleep complaints are common among Iranian chemically-injured veterans. The growing body of research has investigated (in) equalities between such subjective complaints and objective sleep records. Moreover, sleep complaints are associated with depressive symptoms. Depressive symptoms, also, have been frequently reported in chemically-injured veterans. Therefore, the purpose of this pilot study was to investigate the relationship between perceived sleep quality, polysomnographic meas...

Effects of lethal and non-lethal malaria on the mononuclear phagocyte system

Directory of Open Access Journals (Sweden)

Carlos Eduardo Tosta

1983-03-01

Full Text Available The effects ofone non-lethal species ofmalarialparasite, Plasmodium yoelii, and one lethal species, P. berghei, on the mononuclear phagocyte system (MPS of BALB/c mice were studied. P. yoelii caused a greater and more sustained expansion and activation of the MPS, and the two major populations of spleen phagocytic cells-red pulp and marginal zone macrophages - exhibited a greater increase in numbers in this infection. During the course of P. berghei mataria, the spleen was progressively occupied by haematopoietic tissue and, at the terminal stage of infection, an extensive depletion of lymphocytes and macrophages was apparent. The possibility was suggested that the outcome of mataria may be inftuenced by the particular way the parasite interacts with the MPS.Estudou-se o efeito da infecção causada por espécie letal (Plasmodium berghei e não- letal (P. yoelii de plasmódio sobre o sistema de fagócitos mononucleares de camundongo BALB/c. O P. yoelii causou maior e mais prolongada expansão e ativação do sistema de macrófagos. As duas mais importantes populações de fagócitos esplênicos - macrófagos de polpa vermelha e da zona marginal - exibiam maior aumento do número de células nesta infecção. Durante a evolução da malária por P. berghei, o baço foi progressivamente ocupado por tecido hematopoiético e, na fase terminal da infecção, observou-se significativa depleção dos linfócitos e macrófagos esplênicos. Os dados apresentados indicam que a evolução da malária depende do tipo de interação entre o plasmódio e o sistema de fagócitos mononucleares.

Metabolic responses of Eisenia fetida after sub-lethal exposure to organic contaminants with different toxic modes of action

Energy Technology Data Exchange (ETDEWEB)

McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda A. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada); Alaee, Mehran [Environment Canada, 867 Lakeshore Rd., P.O. Box 5050, Burlington, ON L7R 4A6 (Canada); Simpson, Andre J. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada); Simpson, Myrna J., E-mail: myrna.simpson@utoronto.ca [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada)

2011-12-15

Nuclear magnetic resonance (NMR) - based metabolomics has the potential to identify toxic responses of contaminants within a mixture in contaminated soil. This study evaluated the metabolic response of Eisenia fetida after exposure to an array of organic compounds to determine whether contaminant-specific responses could be identified. The compounds investigated in contact tests included: two pesticides (carbaryl and chlorpyrifos), three pharmaceuticals (carbamazephine, estrone and caffeine), two persistent organohalogens (Aroclor 1254 and PBDE 209) and two industrial compounds (nonylphenol and dimethyl phthalate). Control and contaminant-exposed metabolic profiles were distinguished using principal component analysis and potential contaminant-specific biomarkers of exposure were found for several contaminants. These results suggest that NMR-based metabolomics offers considerable promise for differentiating between the different toxic modes of action (MOA) associated with sub-lethal toxicity to earthworms. - Highlights: > NMR-based earthworm metabolomic analysis of the toxic mode of action of various environmental contaminants. > Organic chemicals with different toxic modes of action resulted in varied metabolomic responses for E. fetida. > NMR-based metabolomics differentiates between the different modes of action associated with sub-lethal toxicity. - {sup 1}H NMR metabolomics was used to identify potential biomarkers of organic contaminant exposure in Eisenia fetida earthworms.

Dominant lethal and ovarian effects of plutonium-239 in female mice

International Nuclear Information System (INIS)

Searle, A.G.; Beechey, C.V.; Green, D.; Howells, G.R.

1982-01-01

(C3H x 101)F 1 female mice were injected intravenously with 239 Pu in trisodium citrate, then mated in pairs to strain CBA males, to test for dominant lethality. In the first experiment 10μCi kg -1 and in the second 20μCi kg -1 body mass was injected. Matings were after 6 days in the first experiment (estimated ovarian absorbed dose of 0.1 Gy) and after 3,6 or 12 weeks in the second (estimated ovarian doses of 1.11, 2.45 and 5.91 Gy respectively). No evidence of dominant lethal induction was found in the first experiment, but in the second there was a significant increase over controls in pre-implantation loss in all three series. Post-implantation lethality increased significantly (by 12%) only after 12 weeks' exposure. With the 6- and 12-week exposures (especially the latter) luteal counts fell, fewer females becoming pregnant than in controls. This is attributed to oocyte killing by the α-particles. Histological and autoradiographic investigations showed a marked reduction in ovarian size and follicular numbers with fission-tracks clustered mainly over the medullary stroma. The preimplantation loss may stem from lowered fertilization of oocytes because of their damage, so that the best measure of dominant lethality is that based on post-implantation death. (author)

Reduction of radio-contamination of vines by the method of 'non-lethal defoliation'

International Nuclear Information System (INIS)

Arapis, G.

1998-01-01

This study is included in the European Commission Programme RESSAC (Rehabilitation of Soils and Surfaces after a nuclear Accident). Its objective is to investigate the possibility of using 'non-lethal defoliation' as a countermeasure to mitigate the foliar uptake of radionuclides by plant leaves. We experimented on vines in productive agricultural fields in Spata - Attica, Greece. Interception factors and translocation of radionuclides studies were performed by using 134 Cs as marker. The deposition of 134 Cs was dry. Two pesticides, Harvade 60% FL and Basta 20 S.L., were used as defoliants. Our data showed that the recommended commercial doses of these chemicals resulted in defoliating up to 80% of the plants. We observed a reduction of radioactivity translocation to grapes by half, related to the defoliating degree. The efficacy of Harvade seemed higher than that of Basta. (authors)

Non-Lethal Chemical Weapons

National Research Council Canada - National Science Library

Weilacher, Lester A

2003-01-01

Little more than a month after terrorists took control of four passenger aircraft in the United States and unleashed the horror of 9/11, 50 Chechen terrorists armed with automatic weapons and carrying...

Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy.

Science.gov (United States)

Kandadi, Machender R; Yu, Xuejun; Frankel, Arthur E; Ren, Jun

2012-11-07

Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Wild type (WT) and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.)). Cardiomyocyte contractile and intracellular Ca(2+) properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca(2+) handling), the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca(2+) anomalies, possibly through regulation of autophagy and mitochondrial function.

Pedigree analyses of yeast cells recovering from DNA damage allow assignment of lethal events to individual post-treatment generations

International Nuclear Information System (INIS)

Klein, F.; Karwan, A.; Wintersberger, U.

1990-01-01

Haploid cells of Saccharomyces cerevisiae were treated with different DNA damaging agents at various doses. A study of the progeny of individual such cells allowed the assignment of lethal events to distinct post treatment generations. By microscopically inspecting those cells which were not able to form visible colonies the authors could discriminate between cells dying from immediately effective lethal hits and those generating microcolonies probably as a consequence of lethal mutation(s). The experimentally obtained numbers of lethal events were mathematically transformed into mean probabilities of lethal fixations at taking place in cells of certain post treatment generations. Such analyses give detailed insight into the kinetics of lethality as a consequence of different kinds of DNA damage. For example, X-irradiated cells lost viability mainly by lethal hits, only at a higher dose also lethal mutations fixed in the cells that were in direct contact with the mutagen, but not in later generations, occurred. Ethyl methanesulfonate (EMS)-treated cells were hit by 00-fixations in a dose dependent manner. The distribution of all sorts of lethal fixations taken together, which occurred in the EMS-damaged cell families, was not random. For comparison analyses of cells treated with methyl methanesulfonate, N-methyl-N'-nitro-N-nitrosoguanidine and nitrous acid are also reported

Fine Mapping and Transcriptome Analysis Reveal Candidate Genes Associated with Hybrid Lethality in Cabbage (Brassica Oleracea).

Science.gov (United States)

Xiao, Zhiliang; Hu, Yang; Zhang, Xiaoli; Xue, Yuqian; Fang, Zhiyuan; Yang, Limei; Zhang, Yangyong; Liu, Yumei; Li, Zhansheng; Liu, Xing; Liu, Zezhou; Lv, Honghao; Zhuang, Mu

2017-06-05

Hybrid lethality is a deleterious phenotype that is vital to species evolution. We previously reported hybrid lethality in cabbage ( Brassica oleracea ) and performed preliminary mapping of related genes. In the present study, the fine mapping of hybrid lethal genes revealed that BoHL1 was located on chromosome C1 between BoHLTO124 and BoHLTO130, with an interval of 101 kb. BoHL2 was confirmed to be between insertion-deletion (InDels) markers HL234 and HL235 on C4, with a marker interval of 70 kb. Twenty-eight and nine annotated genes were found within the two intervals of BoHL1 and BoHL2 , respectively. We also applied RNA-Seq to analyze hybrid lethality in cabbage. In the region of BoHL1 , seven differentially expressed genes (DEGs) and five resistance (R)-related genes (two in common, i.e., Bo1g153320 and Bo1g153380 ) were found, whereas in the region of BoHL2 , two DEGs and four R-related genes (two in common, i.e., Bo4g173780 and Bo4g173810 ) were found. Along with studies in which R genes were frequently involved in hybrid lethality in other plants, these interesting R-DEGs may be good candidates associated with hybrid lethality. We also used SNP/InDel analyses and quantitative real-time PCR to confirm the results. This work provides new insight into the mechanisms of hybrid lethality in cabbage.

Potentially lethal damage and its repair

International Nuclear Information System (INIS)

Utsumi, Hiroshi

1989-01-01

Two forms termed fast-and slow-potentially lethal lethal damage (PLD) are introduced and discussed. The effect on the survival of x-irradiated Chinese hamster cells (V79) of two different post-treatments is examined in plateau- and in log-phases of growth. The postirradiation treatments used : a) incubation in hypertonic solution, and b) incubation in conditioned medium obtained from plateau-phase. Similar reduction in survival was caused by postirradiation treatment with hypertonic phosphate buffered saline, and similar increased in survival was effected by treatment in conditioned medium in plateau- and in log-phases cells. However, repair of PLD sensitive to hypertonic treatment was faster (half time, 5-10 min)(f-PLD repair) and independent from the repair of PLD (half time, 1-2 hour)(s-PLD repair) observed in conditioned medium. The results indicate the induction of two forms of PLD by radiation. Induction of both PLD was found to decrease with increasing LET of the radiation used. Identification of the molecular processes underlying repair and fixation of PLD is a task of particular interest, since it may allow replacement of a phenomenological definition with a molecular definition. Evidence is reviewed indicating the DNA double strand breaks (directly or indirectly induced) may be the DNA lesions underlying PLD. (author)

Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy

Directory of Open Access Journals (Sweden)

Kandadi Machender R

2012-11-01

Full Text Available Abstract Background Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Methods Wild type (WT and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.. Cardiomyocyte contractile and intracellular Ca2+ properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Results Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca2+ handling, the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Conclusions Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca2+ anomalies, possibly through regulation of autophagy and mitochondrial function.

Linear solvation energy relationships for toxicity of selected organic chemicals to Daphnia pulex and Daphnia magna

Science.gov (United States)

Passino, Dora R.M.; Hickey, James P.; Frank, Anthony M.

1988-01-01

In the Laurentian Great Lakes, more than 300 contaminants have been identified in fish, other biota, water, and sediment. Current hazard assessment of these chemicals by the National Fisheries Research Center-Great Lakes is based on their toxicity, occurrence in the environment, and source. Although scientists at the Center have tested over 70 chemicals with the crustacean Daphnia pulex, the number of experimental data needed to screen the huge array of chemicals in the Great Lakes exceeds the practical capabilities of conducting bioassays. This limitation can be partly circumvented, however, by using mathematical models based on quantitative structure-activity relationships (QSAR) to provide rapid, inexpensive estimates of toxicity. Many properties of chemicals, including toxicity, bioaccumulation and water solubility are well correlated and can be predicted by equations of the generalized linear solvation energy relationships (LSER). The equation we used to model solute toxicity is Toxicity = constant + mVI/100 + s (π* + dδ) + bβm + aαm where VI = intrinsic (Van der Waals) molar volume; π* = molecular dipolarity/polarizability; δ = polarizability 'correction term'; βm = solute hydrogen bond acceptor basicity; and αm = solute hydrogen bond donor acidity. The subscript m designates solute monomer values for α and β. We applied the LSER model to 48-h acute toxicity data (measured as immobilization) for six classes of chemicals detected in Great Lakes fish. The following regression was obtained for Daphnia pulex (concentration = μM): log EC50 = 4.86 - 4.35 VI/100; N = 38, r2 = 0.867, sd = 0.403 We also used the LSER modeling approach to analyze to a large published data set of 24-h acute toxicity for Daphnia magna; the following regression resulted, for eight classes of compounds (concentration = mM): log EC50 = 3.88 - 4.52 VI/100 - 1.62 π* + 1.66 βm - 0.916 αm; N = 62, r2 = 0.859, sd = 0.375 In addition we developed computer software that identifies

Identification of Lilial as a fragrance sensitizer in a perfume by bioassay-guided chemical fractionation and structure-activity relationships

DEFF Research Database (Denmark)

Gimenéz-Arnau, Elena; Andersen, K E; Bruze, M

2000-01-01

Fragrance materials are among the most common causes of allergic contact dermatitis. The aim of this study was to identify in a perfume fragrance allergens not included in the fragrance mix, by use of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships...... (SARs). The basis for the investigation was a 45-year-old woman allergic to her own perfume. She had a negative patch test to the fragrance mix and agreed to participate in the study. Chemical fractionation of the perfume concentrate was used for repeated patch testing and/or repeated open application...

Modification of the repair of potentially lethal damage in plateau-phase Chinese hamster cells by 2-chlorodeoxyadenosine

International Nuclear Information System (INIS)

Tanabe, Kiyoshi; Hiraoka, Wakako; Kuwabara, Mikinori; Matsuda, Akira; Ueda, Tohru; Sato, Fumiaki.

1988-01-01

The ability of 2-chlorodeoxyadenosine, a ribonucleotide reductase inhibitor, to inhibit the repair of potentially lethal damage was demonstrated in Chinese hamster V79 cells after X irradiation in plateau-phase cultures. This ability of the drug was completely diminished when deoxycytidine was added at the same time, though this was slightly affected by the addition of adenosine, suggesting that this drug was phosphorylated by deoxycytidine kinase to serve as an inhibitor of the repair of potentially lethal damage. Compared with hydroxyurea, another ribonucleotide reductase inhibitor, this drug appeared to contain its own activity which suppressed the repair of potentially lethal damage. A combined study of post-irradiation treatment with hypertonic salt solution and with this drug on the fixation of potentially lethal damage revealed that this drug inhibited the repair of hypertonic-insensitive potentially lethal damage. (author)

Modification of the repair of potentially lethal damage in plateau-phase Chinese hamster cells by 2-chlorodeoxyadenosine

Energy Technology Data Exchange (ETDEWEB)

Tanabe, Kiyoshi; Hiraoka, Wakako; Kuwabara, Mikinori; Matsuda, Akira; Ueda, Tohru; Sato, Fumiaki.

1988-09-01

The ability of 2-chlorodeoxyadenosine, a ribonucleotide reductase inhibitor, to inhibit the repair of potentially lethal damage was demonstrated in Chinese hamster V79 cells after X irradiation in plateau-phase cultures. This ability of the drug was completely diminished when deoxycytidine was added at the same time, though this was slightly affected by the addition of adenosine, suggesting that this drug was phosphorylated by deoxycytidine kinase to serve as an inhibitor of the repair of potentially lethal damage. Compared with hydroxyurea, another ribonucleotide reductase inhibitor, this drug appeared to contain its own activity which suppressed the repair of potentially lethal damage. A combined study of post-irradiation treatment with hypertonic salt solution and with this drug on the fixation of potentially lethal damage revealed that this drug inhibited the repair of hypertonic-insensitive potentially lethal damage.

A reliable method for reconstituting thymectomized, lethally irradiated guinea pigs with bone marrow cells

International Nuclear Information System (INIS)

Terata, N.; Tanio, Y.; Zbar, B.

1984-01-01

The authors developed a reliable method for reconstituting thymectomized, lethally irradiated guinea pigs. Injection of 2.5-10 x 10 7 syngeneic bone marrow cells into adult thymectomized, lethally irradiated guinea pigs produced survival of 46-100% of treated animals. Gentamycin sulfate (5 mg/kg of body weight) for 10 days was required for optimal results. Acidified drinking water (pH 2.5) appeared to be required for optimal results. Thymectomized, lethally irradiated, bone marrow reconstituted ('B') guinea pigs had impaired ability to develop delayed cutaneous hypersensitivity to mycobacterial antigens and cutaneous basophil hypersensitivity to keyhole limpet hemocyanin; proliferative responses to phytohemagglutinin were impaired. (Auth.)

Lethal concentrations of heavy metals in tissue of earthworms. Interim report No. 1, June-July 1987

Energy Technology Data Exchange (ETDEWEB)

Bouche, M.B.; Brun, P.; Gal, J.Y.; Reza, A.

1987-07-01

The objective of this phase of Toxicological Research on Lethal Concentrations of Heavy Metals in Tissue of Earthworms is to improve both ecotoxicological tests in a chemically defined medium and a procedure of bioavailability study in field. In this first period the authors worked on breeding stock of earthworms (species Eisenia fetida andrei) in decomposing manure heaps to increase them and make them grow. They also installed two chambers with thermostats fixed at 20 C to do toxicity tests and chose chemical species of heavy-metal contaminants. For field procedure, they improved a practical way to sample both earthworms and soil in very close connections, avoiding artifacts. For both field procedure and laboratory tests, they tried to standardize a method to dissolve earthworms in acids and to analyze the concentrations of heavy metals inside. A preliminary set of samples in calcareous soils was started and analysis of them are in progress. For lab tests, the first part of the test (preliminary test) was started with the different contaminants (cadmium, copper, arsenic, mercury) in an artificial medium named Artisol.

Beliefs and attitudes toward lethal management of deer in Cuyahoga Valley National Park

Science.gov (United States)

Fulton, D.C.; Skerl, K.; Shank, E.M.; Lime, D.W.

2004-01-01

We used the theory of reasoned action to help understand attitudes and beliefs about lethal management of deer (Odocoileus virginianus) in Cuyahoga Valley National Park (CVNP), Ohio. We used a mail-back survey to collect data from Ohio residents in the surrounding 9-county area. Two strata were defined: residents control of deer was acceptable (near 71%??4.7%, far 62%??5.5%) and taking no action to reduce deer populations was unacceptable (near 75%??4.5%, far 72%??5.1%). Beliefs about outcomes of lethal control and evaluation of those outcomes proved to be strong predictors of the acceptability of lethal control of deer in CVNP. Lethal control was more acceptable if it was done to prevent severe consequences for humans (e.g., spread of disease, car collisions) or the natural environment (e.g., maintain a healthy deer herd) than to prevent negative aesthetic impacts or personal property damage. Results from the study can be used to assist managers at CVNP as they make decisions regarding alternatives for deer management in the park and to inform others managing abundant deer populations of socially relevant impacts of management actions.

Papaya Lethal Yellowing Virus (PLYV) Infects Vasconcellea cauliflora

NARCIS (Netherlands)

Amaral, P.P.R.; Resende, de R.O.; Souza, M.T.

2006-01-01

Papaya lethal yellowing virus (PLYV) é um dos três vírus descritos infectando mamoeiros (Carica papaya L.) no Brasil. Vasconcellea cauliflora (Jacq.) A. DC., antes denominada de Carica cauliflora (Jacq.), é uma reconhecida fonte de resistência natural ao Papaya ringspot virus (PRSV), causador da

Lethal Surveillance: Drones and the Geo-History of Modern War

Science.gov (United States)

Kindervater, Katharine Hall

Interdisciplinary both in scope and method, my dissertation, Lethal Surveillance: Drones and the Geo-History of Modern War, examines the history of drone technology from the start of the 20th century to the present in order to understand the significance of the increasing centrality of drones to current American military engagements and security practices more generally. Much of the scholarship on drones and many other contemporary military technologies tends to view the technology as radically new, missing both the historical development of these objects as well as the perspectives and rationalities that are embedded in their use. For this research, I focused on three main periods of drone research and development: the early years of World War I and II in the UK, the Cold War, and the 1990s. In studying this history of the drone, I found that two key trends emerge as significant: the increasing importance of information to warfare under the rubric of intelligence, reconnaissance and surveillance; and a shift toward more dynamic, speedier, and individualized targeting practices. I argue that the widespread use of drones today thus represents the culmination of attempts in war to effectively link these two trends, creating a practice I call lethal surveillance -- with the armed Predator effectively closing the loop between identifying and killing targets. The concept of lethal surveillance, which in my dissertation I place squarely within the histories of modern scientific thinking and Western liberal governance, allows us to see how techniques of Western state power and knowledge production are merging with practices of killing and control in new ways, causing significant changes to both the operations of the state and to practices of war. Framing the drone through the lens of lethal surveillance, therefore, allows us to see the longer histories the drone is embedded in as well as other security practices it is connected to.

1H NMR-based metabolomics of time-dependent responses of Eisenia fetida to sub-lethal phenanthrene exposure

International Nuclear Information System (INIS)

Lankadurai, Brian P.; Wolfe, David M.; Simpson, Andre J.; Simpson, Myrna J.

2011-01-01

1 H NMR-based metabolomics was used to examine the response of the earthworm Eisenia fetida after exposure to sub-lethal concentrations of phenanthrene over time. Earthworms were exposed to 0.025 mg/cm 2 of phenanthrene (1/64th of the LC 50 ) via contact tests over four days. Earthworm tissues were extracted using a mixture of chloroform, methanol and water, resulting in polar and non-polar fractions that were analyzed by 1 H NMR after one, two, three and four days. NMR-based metabolomic analyses revealed heightened E. fetida responses with longer phenanthrene exposure times. Amino acids alanine and glutamate, the sugar maltose, the lipids cholesterol and phosphatidylcholine emerged as potential indicators of phenanthrene exposure. The conversion of succinate to fumarate in the Krebs cycle was also interrupted by phenanthrene. Therefore, this study shows that NMR-based metabolomics is a powerful tool for elucidating time-dependent relationships in addition to the mode of toxicity of phenanthrene in earthworm exposure studies. - Highlights: → NMR-based earthworm metabolomic analysis of the mode of action of phenanthrene is presented. → The earthworm species E. fetida were exposed to sub-lethal phenanthrene concentrations. → Both polar and non-polar metabolites of E. fetida tissue extracts were analyzed by 1 H NMR. → Longer phenanthrene exposure times resulted in heightened earthworm responses. → An interruption of the Krebs cycle was also observed due to phenanthrene exposure. - 1 H NMR metabolomics is used to determine the relationship between phenanthrene exposure and the metabolic response of the earthworm E. fetida over time and also to elucidate the phenanthrene mode of toxicity.

The changing employment relationship in the chemical industry : the role of the employment- and psychological contract / Elsabé Keyser.

OpenAIRE

Keyser, Elsabé

2010-01-01

Understanding the employment relationship in the chemical industry in South Africa and organisational change within it is crucial to the understanding of the changing employment and psychological contract within this industry. This study focused on the employment- and psychological contracts, as well as employees ' work-outcomes (organisational commitment, job insecurity, job performance and intention to quit). Employees from the chemical industry were targeted and a cross-sectional survey...

Metabolic responses of Eisenia fetida after sub-lethal exposure to organic contaminants with different toxic modes of action

International Nuclear Information System (INIS)

McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda A.; Alaee, Mehran; Simpson, Andre J.; Simpson, Myrna J.

2011-01-01

Nuclear magnetic resonance (NMR) - based metabolomics has the potential to identify toxic responses of contaminants within a mixture in contaminated soil. This study evaluated the metabolic response of Eisenia fetida after exposure to an array of organic compounds to determine whether contaminant-specific responses could be identified. The compounds investigated in contact tests included: two pesticides (carbaryl and chlorpyrifos), three pharmaceuticals (carbamazephine, estrone and caffeine), two persistent organohalogens (Aroclor 1254 and PBDE 209) and two industrial compounds (nonylphenol and dimethyl phthalate). Control and contaminant-exposed metabolic profiles were distinguished using principal component analysis and potential contaminant-specific biomarkers of exposure were found for several contaminants. These results suggest that NMR-based metabolomics offers considerable promise for differentiating between the different toxic modes of action (MOA) associated with sub-lethal toxicity to earthworms. - Highlights: → NMR-based earthworm metabolomic analysis of the toxic mode of action of various environmental contaminants. → Organic chemicals with different toxic modes of action resulted in varied metabolomic responses for E. fetida. → NMR-based metabolomics differentiates between the different modes of action associated with sub-lethal toxicity. - 1 H NMR metabolomics was used to identify potential biomarkers of organic contaminant exposure in Eisenia fetida earthworms.

Influence Of Quinolone Lethality on Irradiated Anaerobic Growth of Escherichia Coli

International Nuclear Information System (INIS)

Ibrahim, I.M.; El-Kabbany, H.M.; El-Esseily, E.SH.

2012-01-01

Bacteriostatic and bactericidal activities were measured with wild type cells and isomerase mutants of Escherichia coli for ciprofloxacin, formation of quinolone-gyrase-DNA complexes, observed as a sodium dodecyl sulfate (SDS) dependent drop in cell lysate viscosity, occurred during aerobic and anaerobic growth and in the presence and in the absence of chloramphenicol. Quinolone activity against Escherichia coli was examined during aerobic growth, aerobic treatment with chloramphenicol, and anaerobic growth. Nalidixic acid, norfloxacin and ciprofloxacin were lethal for cultures growing aerobically, and the bacteriostatic activity of each quinolone was unaffected by anaerobic growth. However, lethal activity was distinct for each quinolone with cells treated aerobically with chloramphenicol or grown anaerobically. Nalidixic acid failed to kill cells under both conditions, norfloxacin killed cells when they were grown anaerobically but not when they were treated with chloramphenicol, ciprofloxacin killed cells under both conditions but required higher concentrations than those required with cells grown aerobically, C-methoxy fluoro quinolone was equally lethal under all conditions. However, lethal chromosome fragmentation, detected as a drop in viscosity in the absence of SDS, was occurred with nalidixic acid treatment only under aerobic conditions in the absence of chloramphenicol, thus, all quinolones tested appeared to form reversible bacteriostatic complexes containing broken DNA during aerobic growth, during anaerobic growth, and when protein synthesis is blocked. The ability to fragment chromosomes rapidly kill cells under these conditions depends on quinolone structure. The radiation of sublethal dose was 3 Gy at rate of 0.6 Gy/min was shown as non-significant result

Neonatal lethal dwarfism with distinct skeletal malformations - a separate entity?

Energy Technology Data Exchange (ETDEWEB)

Rosendahl, K.; Maurseth, K.; Olsen, Oe.E. [Dept. of Paediatric Radiology, Haukeland University Hospital, Bergen (Norway); Halvorsen, O.J. [Dept. of Pathology, Haukeland University Hospital, Bergen (Norway); Gjelland, K. [Dept. of Gynaecology, Haukeland University Hospital, Bergen (Norway); Engebretsen, L. [Dept. of Genetics, Haukeland University Hospital, Bergen (Norway)

2001-09-01

We describe a case of neonatal lethal dwarfism characterised by short trunk, short, stick-like tubular bones, deficient ossification of the axial skeleton and broad, sclerotic horizontal ribs. Two similar cases have previously been reported as examples of the Neu-Laxova syndrome. However, the radiological findings of the Neu-Laxova syndrome, as reported in 16 out of 40 documented cases, show a heterogeneous pattern of minor features, which differ distinctively from those found in the previous two cases and by us. A literature research did not reveal similar cases, and we therefore suggest that our case, together with the two previous cases, may represent a new distinctive form of neonatal lethal dwarfism. (orig.)

Neonatal lethal dwarfism with distinct skeletal malformations - a separate entity?

International Nuclear Information System (INIS)

Rosendahl, K.; Maurseth, K.; Olsen, Oe.E.; Halvorsen, O.J.; Gjelland, K.; Engebretsen, L.

2001-01-01

We describe a case of neonatal lethal dwarfism characterised by short trunk, short, stick-like tubular bones, deficient ossification of the axial skeleton and broad, sclerotic horizontal ribs. Two similar cases have previously been reported as examples of the Neu-Laxova syndrome. However, the radiological findings of the Neu-Laxova syndrome, as reported in 16 out of 40 documented cases, show a heterogeneous pattern of minor features, which differ distinctively from those found in the previous two cases and by us. A literature research did not reveal similar cases, and we therefore suggest that our case, together with the two previous cases, may represent a new distinctive form of neonatal lethal dwarfism. (orig.)

Pacman dysplasia: a lethal skeletal dysplasia with variable radiographic features

Energy Technology Data Exchange (ETDEWEB)

Miller, S.F. [Dept. of Radiology, Children' s Hospital of the King' s Daughters, Norfolk (United States); Proud, V.K. [Dept. of Genetics, Children' s Hospital of the King' s Daughters, Norfolk (United States); Werner, A.L. [Dept. of Pathology, Children' s Hospital of the King' s Daughters, Norfolk (United States); Field, F.M.; Wilcox, W.F.; Lachman, R.S.; Rimoin, D.L. [International Skeletal Dysplasia Registry, Cedars-Sinai Medical Center, Los Angeles (United States)

2003-04-01

Background: Punctate or stippled cartilaginous calcifications are associated with many conditions, including chromosomal, infectious, endocrine, and teratogenic etiologies. Some of these conditions are clinically mild, while others are lethal. Accurate diagnosis can prove instrumental in clinical management and in genetic counseling. Objective: To describe the diagnostic radiographic features seen in Pacman dysplasia, a distinct autosomal recessive, lethal skeletal dysplasia. Materials and methods: We present the fourth reported case of Pacman dysplasia and compare the findings seen in our patient with the three previously described patients. Results: Invariable and variable radiographic findings were seen in all four cases of histologically proven Pacman dysplasia. Conclusion: Pacman dysplasia presents both constant and variable diagnostic radiographic features. (orig.)

QTL mapping of inbreeding-related cold sensitivity and conditional lethality in Drosophila melanogaster

DEFF Research Database (Denmark)

Vermeulen, Corneel J.; Bijlsma, R.; Loeschcke, Volker

2008-01-01

of inbreeding-related and conditionally expressed lethality in Drosophila melanogaster. The lethal effect was triggered by exposure to a cold shock. We used a North Carolina crossing Design 3 to establish the mapping population, as well as to estimate the average dominance ratio and heritability. We found two......Inbreeding depression is a central theme within genetics, and is of specific interest for researchers within evolutionary and conservation genetics and animal and plant breeding. Inbreeding effects are thought to be caused by the joint expression of conditional and unconditional deleterious alleles....... Whenever the expression of deleterious alleles is conditional, this can result in extreme environmental sensitivity in certain inbred lineages. Analysis of conditional lethal effects can reveal some of the loci that are sensitive to inbreeding. We performed a QTL (quantitative trait locus) mapping study...

Dominant lethal mutations research in mice fed with irradiated black beams

International Nuclear Information System (INIS)

Andrade, Z.P.

1982-01-01

To evaluate the potential mutagenic effects of irradiated black beans (Phaseolus vulgaris) with conservation purpose, in germ cells of mice, dominant lethal assay were employed. Three groups of albino swiss male mice (S W-55) were fed with a normal ration, or unirradiated or irradiated (0,2; 0,5; 1; 5; 10; 15 e 20 KGy) test diets for eight weeks. After the feeding period the males were mated with groups of untreated females mice for four consecutive weeks. Numbers of pregnancy rates females were observed. The females were autopsied at mid-term pregnancy for evaluation of dominant lethal mutations. (author)

Comparative analysis of pharmaceuticals versus industrial chemicals acute aquatic toxicity classification according to the United Nations classification system for chemicals. Assessment of the (Q)SAR predictability of pharmaceuticals acute aquatic toxicity and their predominant acute toxic mode-of-action.

Science.gov (United States)

Sanderson, Hans; Thomsen, Marianne

2009-06-01

Pharmaceuticals have been reported to be ubiquitously present in surface waters prompting concerns of effects of these bioactive substances. Meanwhile, there is a general scarcity of publicly available ecotoxicological data concerning pharmaceuticals. The aim of this paper was to compile a comprehensive database based on OECD's standardized measured ecotoxicological data and to evaluate if there is generally cause of greater concern with regards to pharmaceutical aquatic toxicological profiles relative to industrial chemicals. Comparisons were based upon aquatic ecotoxicity classification under the United Nations Global Harmonized System for classification and labeling of chemicals (GHS). Moreover, we statistically explored whether the predominant mode-of-action (MOA) for pharmaceuticals is narcosis. We found 275 pharmaceuticals with 569 acute aquatic effect data; 23 pharmaceuticals had chronic data. Pharmaceuticals were found to be more frequent than industrial chemicals in GHS category III. Acute toxicity was predictable (>92%) using a generic (Q)SAR ((Quantitative) Structure Activity Relationship) suggesting a narcotic MOA. Analysis of model prediction error suggests that 68% of the pharmaceuticals have a non-specific MOA. Additionally, the acute-to-chronic ratio (ACR) for 70% of the analyzed pharmaceuticals was below 25 further suggesting a non-specific MOA. Sub-lethal receptor-mediated effects may however have a more specific MOA.

Testing of candidate non-lethal sampling methods for detection of Renibacterium salmoninarum in juvenile Chinook salmon Oncorhynchus tshawytscha

Science.gov (United States)

Elliott, Diane G.; McKibben, Constance L.; Conway, Carla M.; Purcell, Maureen K.; Chase, Dorothy M.; Applegate, Lynn M.

2015-01-01

Non-lethal pathogen testing can be a useful tool for fish disease research and management. Our research objectives were to determine if (1) fin clips, gill snips, surface mucus scrapings, blood draws, or kidney biopsies could be obtained non-lethally from 3 to 15 g Chinook salmon Oncorhynchus tshawytscha, (2) non-lethal samples could accurately discriminate between fish exposed to the bacterial kidney disease agent Renibacterium salmoninarum and non-exposed fish, and (3) non-lethal samples could serve as proxies for lethal kidney samples to assess infection intensity. Blood draws and kidney biopsies caused ≥5% post-sampling mortality (Objective 1) and may be appropriate only for larger fish, but the other sample types were non-lethal. Sampling was performed over 21 wk following R. salmoninarum immersion challenge of fish from 2 stocks (Objectives 2 and 3), and nested PCR (nPCR) and real-time quantitative PCR (qPCR) results from candidate non-lethal samples were compared with kidney tissue analysis by nPCR, qPCR, bacteriological culture, enzyme-linked immunosorbent assay (ELISA), fluorescent antibody test (FAT) and histopathology/immunohistochemistry. R. salmoninarum was detected by PCR in >50% of fin, gill, and mucus samples from challenged fish. Mucus qPCR was the only non-lethal assay exhibiting both diagnostic sensitivity and specificity estimates >90% for distinguishing between R. salmoninarum-exposed and non-exposed fish and was the best candidate for use as an alternative to lethal kidney sample testing. Mucus qPCR R. salmoninarum quantity estimates reflected changes in kidney bacterial load estimates, as evidenced by significant positive correlations with kidney R. salmoninaruminfection intensity scores at all sample times and in both fish stocks, and were not significantly impacted by environmentalR. salmoninarum concentrations.

Induction of dominant lethal mutations by gamma irradiation of Gallus domesticus spermatozoa

Energy Technology Data Exchange (ETDEWEB)

Baumgartner, J; Grom, A; Csuka, J; Kindlova, L [Poultry Research Institute, Ivanka pri Dunaji (Czechoslovakia)

1977-01-01

Mixed semen of Gallus domesticus cocks was gamma irradiated in vitro with exposures of 500, 1000, 2000, and 3000 R at the exposure rate of 5.86 Rs/sup -1/. After the irradiation the semen was applied to experimental and control layer hens, the embryonic mortality in F/sub 1/ was observed, the total number of incubated eggs was 3344. Irradiation with 500 R had a favourable influence on embryonic vitality, the exposures 1000, 2000, and 3000 R resulted in increased embryonic mortality, for 2100 R a 50% mortality of offspring was found. Induced dominant lethality was manifest during embryonic and oviduct development. The frequency of induced dominant lethality for exposures used was 19.2, 9.9, 48.3, and 69.1%, the values of mutation rate were 0.087, 0.104, 0.659, and 1.174. The mutation rate had a linear course, the value of the lethal hit per gamete for 1 R was 1.04x10/sup -4/.

Induction of dominant lethal mutations by gamma irradiation of Gallus domesticus spermatozoa

International Nuclear Information System (INIS)

Baumgartner, J.; Grom, A.; Csuka, J.; Kindlova, L.

1977-01-01

Mixed semen of Gallus domesticus cocks was gamma irradiated in vitro with exposures of 500, 1000, 2000 and 3000 R at the exposure rate of 5.86 Rs -1 . After the irradiation the semen was applied to experimental and control layer hens, the embryonic mortality in F 1 was observed, the total number of incubated eggs was 3344. Irradiation with 500 R had a favourable influence on embryonic vitality, the exposures 1000, 2000 and 3000 R resulted in increased embryonic mortality, for 2100 R a 50% mortality of offspring was found. Induced dominant lethality was manifest during embryonic and oviduct development. The frequency of induced dominant lethality for exposures used was 19.2, 9.9, 48.3, and 69.1%, the values of mutation rate were 0.087, 0.104, 0.659, and 1.174. The mutation rate had linear course, the value of the lethal hit per gamete for 1 R was 1.04x10 -4 . (author)

5-Lipoxygenase Deficiency Reduces Acetaminophen-Induced Hepatotoxicity and Lethality

Directory of Open Access Journals (Sweden)

Miriam S. N. Hohmann

2013-01-01

Full Text Available 5-Lipoxygenase (5-LO converts arachidonic acid into leukotrienes (LTs and is involved in inflammation. At present, the participation of 5-LO in acetaminophen (APAP-induced hepatotoxicity and liver damage has not been addressed. 5-LO deficient (5-LO-/- mice and background wild type mice were challenged with APAP (0.3–6 g/kg or saline. The lethality, liver damage, neutrophil and macrophage recruitment, LTB4, cytokine production, and oxidative stress were assessed. APAP induced a dose-dependent mortality, and the dose of 3 g/kg was selected for next experiments. APAP induced LTB4 production in the liver, the primary target organ in APAP toxicity. Histopathological analysis revealed that 5-LO-/- mice presented reduced APAP-induced liver necrosis and inflammation compared with WT mice. APAP-induced lethality, increase of plasma levels of aspartate aminotransferase and alanine aminotransferase, liver cytokine (IL-1β, TNF-α, IFN-γ, and IL-10, superoxide anion, and thiobarbituric acid reactive substances production, myeloperoxidase and N-acetyl-β-D-glucosaminidase activity, Nrf2 and gp91phox mRNA expression, and decrease of reduced glutathione and antioxidant capacity measured by 2,2′-azinobis(3-ethylbenzothiazoline 6-sulfonate assay were prevented in 5-LO-/- mice compared to WT mice. Therefore, 5-LO deficiency resulted in reduced mortality due to reduced liver inflammatory and oxidative damage, suggesting 5-LO is a promising target to reduce APAP-induced lethality and liver inflammatory/oxidative damage.

An improved brine shrimp larvae lethality microwell test method.

Science.gov (United States)

Zhang, Yi; Mu, Jun; Han, Jinyuan; Gu, Xiaojie

2012-01-01

This article described an improved brine shrimp larvae lethality microwell test method. A simply designed connecting vessel with alternative photoperiod was used to culture and collect high yield of active Artemia parthenogenetica nauplii for brine shrimp larvae lethality microwell test. Using this method, pure A. parthenogenetica nauplii suspension was easily cultured and harvested with high density about 100-150 larvae per milliliter and the natural mortality was reduced to near zero by elimination of unnecessary artificial disturbance. And its sensitivity was validated by determination of LC(50)-24 h of different reference toxicants including five antitumor agents, two pesticides, three organic pollutants, and four heavy metals salts, most of which exhibited LC(50)-24 h between 0.07 and 58.43 mg/L except for bleomycin and mitomycin C with LC(50)-24 h over 300 mg/L.

Assessing dose-response relationships for endocrine disrupting chemicals (EDCs): a focus on non-monotonicity.

Science.gov (United States)

Zoeller, R Thomas; Vandenberg, Laura N

2015-05-15

The fundamental principle in regulatory toxicology is that all chemicals are toxic and that the severity of effect is proportional to the exposure level. An ancillary assumption is that there are no effects at exposures below the lowest observed adverse effect level (LOAEL), either because no effects exist or because they are not statistically resolvable, implying that they would not be adverse. Chemicals that interfere with hormones violate these principles in two important ways: dose-response relationships can be non-monotonic, which have been reported in hundreds of studies of endocrine disrupting chemicals (EDCs); and effects are often observed below the LOAEL, including all environmental epidemiological studies examining EDCs. In recognition of the importance of this issue, Lagarde et al. have published the first proposal to qualitatively assess non-monotonic dose response (NMDR) relationships for use in risk assessments. Their proposal represents a significant step forward in the evaluation of complex datasets for use in risk assessments. Here, we comment on three elements of the Lagarde proposal that we feel need to be assessed more critically and present our arguments: 1) the use of Klimisch scores to evaluate study quality, 2) the concept of evaluating study quality without topical experts' knowledge and opinions, and 3) the requirement of establishing the biological plausibility of an NMDR before consideration for use in risk assessment. We present evidence-based logical arguments that 1) the use of the Klimisch score should be abandoned for assessing study quality; 2) evaluating study quality requires experts in the specific field; and 3) an understanding of mechanisms should not be required to accept observable, statistically valid phenomena. It is our hope to contribute to the important and ongoing debate about the impact of NMDRs on risk assessment with positive suggestions.

Lethal midline granuloma syndrome: a diagnostic dilemma

International Nuclear Information System (INIS)

Ribeiro, Bruno Niemeyer de Freitas; Bahia, Paulo Roberto Valle; Oliveira, Ana Luiza Vianna Sobral de Magalhaes; Marchon Junior, Joao Luiz

2012-01-01

The rare lethal midline granuloma syndrome is difficult to diagnose because of the wide array of related diseases and lack of knowledge by the majority of physicians. In the present report, the authors describe the case of a patient with this disease, caused by squamous cell carcinoma, drawing attention to differential diagnoses and to clinical and radiological findings that may be useful to define the diagnosis. (author)

Lethal midline granuloma syndrome: a diagnostic dilemma

Energy Technology Data Exchange (ETDEWEB)

Ribeiro, Bruno Niemeyer de Freitas; Bahia, Paulo Roberto Valle [Radiology, Hospital Universitario Clementino Fraga Filho - Universidade Federal do Rio de Janeiro (HUCFF-UFRJ), Rio de Janeiro, RJ (Brazil); Oliveira, Ana Luiza Vianna Sobral de Magalhaes [Resident of Medical Practice, Hospital Federal da Lagoa, Rio de Janeiro, RJ (Brazil); Marchon Junior, Joao Luiz [Unit of Computed Tomography, Hospital Federal da Lagoa, Rio de Janeiro, RJ (Brazil)

2012-11-15

The rare lethal midline granuloma syndrome is difficult to diagnose because of the wide array of related diseases and lack of knowledge by the majority of physicians. In the present report, the authors describe the case of a patient with this disease, caused by squamous cell carcinoma, drawing attention to differential diagnoses and to clinical and radiological findings that may be useful to define the diagnosis. (author)

Development of non-lethal methods for investigation of actinide uptake by wildlife

Energy Technology Data Exchange (ETDEWEB)

Johansen, M.; Child, D.; Davis, E.; Harrison, J.; Hotchkis, M.; Payne, T.; Thiruvoth, S. [Australian Nuclear Science and Technology Org. (Australia); Wood, M. [University of Salford (United Kingdom)

2014-07-01

There is growing interest in the use of non-lethal methods in radioecology and an International Union of Radioecology Task Group has been established to facilitate international cooperation in this field (http://iur-uir.org/en/task-groups/id-19-non-lethal-methods-in-radioecology). In this paper, we evaluate the use of lethally-, and non-lethally obtained samples (various body tissues, excreta and blood withdrawals as well as parasites and found bones) as indicators of contamination. Samples of mammals and reptiles were collected from the semi-arid former weapons test site at Maralinga, Australia and analysed for thorium, plutonium, and uranium isotopes by accelerator mass spectrometry and alpha-spectrometry. Most samples were of low mass and presented analytical challenges as a result. The plutonium concentrations in blood withdrawn from the marginal ear veins of Oryctolagus cuniculus (European rabbit) were successfully analysed using small samples (0.2 -7.9 ml, below the ∼10 ml threshold for safe extraction of blood from these rabbits). The results demonstrate that small-volume blood samples can serve as indicators of the presence of plutonium absorbed within other tissues (e.g., muscle, bone). However, the magnitude of the blood plutonium masses were poorly correlated with those in muscle and bone due to the presence of a small number of outliers (without the outliers, correlations improved to r = +0.66 and r = +0.51 for muscle and bone respectively). The activity concentrations in parasitic ticks were relatively high compared with those of their hosts Pseudomys hermannsburgensis (sandy inland mouse) and Ctenophorus cristatus (crested dragon lizard). Successful measurement of tick samples indicates a potential for use of parasites as general indicators of contamination within host organisms. The concentrations of actinides in found bones of Macropus rufus (red kangaroo) and O. cuniculus demonstrated potential for their use as indicators of the areal extent of

Tolerization with BLP down-regulates HMGB1 a critical mediator of sepsis-related lethality.

LENUS (Irish Health Repository)

Coffey, J Calvin

2012-02-03

Tolerization with bacterial lipoprotein (BLP) affords a significant survival benefit in sepsis. Given that high mobility group box protein-1 (HMGB1) is a recognized mediator of sepsis-related lethality, we determined if tolerization with BLP leads to alterations in HMGB1. In vitro, BLP tolerization led to a reduction in HMGB1 gene transcription. This was mirrored at the protein level, as HMGB1 protein expression and release were reduced significantly in BLP-tolerized human THP-1 monocytic cells. BLP tolerance in vivo led to a highly significant, long-term survival benefit following challenge with lethal dose BLP in C57BL\\/6 mice. This was associated with an attenuation of HMGB1 release into the circulation, as evidenced by negligible serum HMGB1 levels in BLP-tolerized mice. Moreover, HMGB1 levels in peritoneal macrophages from BLP-tolerized mice were reduced significantly. Hence, tolerization with BLP leads to a down-regulation of HMGB1 protein synthesis and release. The improved survival associated with BLP tolerance could thus be explained by a reduction in HMGB1, were the latter associated with lethality in BLP-related sepsis. In testing this hypothesis, it was noted that neutralization of HMGB1, using anti-HMGB1 antibodies, abrogated BLP-associated lethality almost completely. To conclude, tolerization with BLP leads to a down-regulation of HMGB1, thus offering a novel means of targeting the latter. HMGB1 is also a mediator of lethality in BLP-related sepsis.

[Gunshot wounds caused by non-lethal ammunition on the porcine model post-mortem].

Science.gov (United States)

Jabrocký, Peter; Pivko, Juraj; Vondráková, Mária; Tažký, Boris

2013-10-01

In this article we focus on the effects of so called non-lethal ammunition. We studied possible mechanism of firearm injury formation as a consequence of using firearm on the body, to present a more comprehensive material in wound ballistics. We pointed out possible actions of a projectile causes on human, respectively other animal organisms, as well as to a manner in which an injury is caused by rifles or shotguns using non-lethal ammunition with rubber projectiles. In the experiment, we have focused on macroscopic analysis of the tissue penetrated by a rubber projectile fired from a long firearm and pump-action shotgun while focusing on the anatomical-morphological analysis of entry wounds to determine the effectiveness respectively, the wounding potential of the projectile. The results of the experiment based on the macroscopic analysis of entry wounds, cavities and exit wounds, show that when a rubber projectile penetrates the body it causes loss of the tissue (i.e. the minus effect) and mechanical disruption of the tissue similar to lethal projectile. Based on the measures and ballistic computations we concluded that in specific cases, like for example in a close range hit, a penetration of vital organs can cause serious or even lethal injuries.

Anti-Cancer Drug Discovery Using Synthetic Lethal Chemogenetic (SLC) Analysis

National Research Council Canada - National Science Library

Bellows, David S

2004-01-01

I am developing a novel cell-based small-molecule screening approach that can identify inhibitors of any non-essential protein function through a surrogate synthetic lethal phenotype in the baker's...

Anti-Cancer Drug Discovery Using Synthetic Lethal Chemogenetic (SLC) Analysis

National Research Council Canada - National Science Library

Bellows, David S

2006-01-01

I am developing a novel cell-based small-molecule screening approach that can identify inhibitors of any non-essential protein function through a surrogate synthetic lethal phenotype in the baker's...

Immune Protection against Lethal Fungal-Bacterial Intra-Abdominal Infections.

Science.gov (United States)

Lilly, Elizabeth A; Ikeh, Melanie; Nash, Evelyn E; Fidel, Paul L; Noverr, Mairi C

2018-01-16

Polymicrobial intra-abdominal infections (IAIs) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation with Candida albicans or other virulent non- albicans Candida (NAC) species plus Staphylococcus aureus resulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis). Surprisingly, inoculation with Candida dubliniensis or Candida glabrata with S. aureus resulted in minimal mortality, and rechallenge of these mice with lethal C. albicans / S. aureus (i.e., coninfection) resulted in >90% protection. The purpose of this study was to define requirements for C. dubliniensis / S. aureus -mediated protection and interrogate the mechanism of the protective response. Protection was conferred by C. dubliniensis alone or by killed C. dubliniensis plus live S. aureus S. aureus alone was not protective, and killed S. aureus compromised C. dubliniensis -induced protection. C. dubliniensis / S. aureus also protected against lethal challenge by NAC plus S. aureus and could protect for a long-term duration (60 days between primary challenge and C. albicans/S. aureus rechallenge). Unexpectedly, mice deficient in T and B cells (Rag-1 knockouts [KO]) survived both the initial C. dubliniensis/S. aureus challenge and the C. albicans/S. aureus rechallenge, indicating that adaptive immunity did not play a role. Similarly, mice depleted of macrophages prior to rechallenge were also protected. In contrast, protection was associated with high numbers of Gr-1 hi polymorphonuclear leukocytes (PMNLs) in peritoneal lavage fluid within 4 h of rechallenge, and in vivo depletion of Gr-1 + cells prior to rechallenge abrogated protection. These results suggest that Candida species can induce protection against a lethal C. albicans / S. aureus IAI that is mediated by PMNLs and postulated to be a unique form of

76 FR 6054 - Use of Less-Than-Lethal Force: Delegation

Science.gov (United States)

2011-02-03

... report any medical problems encountered by subjects being subdued and arrested, and no medical problems.... Therefore, for accuracy in terminology, we replace the term ``non-lethal'' with the more accurate term...

{sup 1}H NMR-based metabolomics of time-dependent responses of Eisenia fetida to sub-lethal phenanthrene exposure

Energy Technology Data Exchange (ETDEWEB)

Lankadurai, Brian P.; Wolfe, David M.; Simpson, Andre J. [Department of Chemistry, University of Toronto, 1265 Military Trail, Toronto, Ontario M1C 1A4 Canada (Canada); Simpson, Myrna J., E-mail: myrna.simpson@utoronto.ca [Department of Chemistry, University of Toronto, 1265 Military Trail, Toronto, Ontario M1C 1A4 Canada (Canada)

2011-10-15

{sup 1}H NMR-based metabolomics was used to examine the response of the earthworm Eisenia fetida after exposure to sub-lethal concentrations of phenanthrene over time. Earthworms were exposed to 0.025 mg/cm{sup 2} of phenanthrene (1/64th of the LC{sub 50}) via contact tests over four days. Earthworm tissues were extracted using a mixture of chloroform, methanol and water, resulting in polar and non-polar fractions that were analyzed by {sup 1}H NMR after one, two, three and four days. NMR-based metabolomic analyses revealed heightened E. fetida responses with longer phenanthrene exposure times. Amino acids alanine and glutamate, the sugar maltose, the lipids cholesterol and phosphatidylcholine emerged as potential indicators of phenanthrene exposure. The conversion of succinate to fumarate in the Krebs cycle was also interrupted by phenanthrene. Therefore, this study shows that NMR-based metabolomics is a powerful tool for elucidating time-dependent relationships in addition to the mode of toxicity of phenanthrene in earthworm exposure studies. - Highlights: > NMR-based earthworm metabolomic analysis of the mode of action of phenanthrene is presented. > The earthworm species E. fetida were exposed to sub-lethal phenanthrene concentrations. > Both polar and non-polar metabolites of E. fetida tissue extracts were analyzed by {sup 1}H NMR. > Longer phenanthrene exposure times resulted in heightened earthworm responses. > An interruption of the Krebs cycle was also observed due to phenanthrene exposure. - {sup 1}H NMR metabolomics is used to determine the relationship between phenanthrene exposure and the metabolic response of the earthworm E. fetida over time and also to elucidate the phenanthrene mode of toxicity.

Wood Chemical Composition in Species of Cactaceae: The Relationship between Lignification and Stem Morphology

Science.gov (United States)

Canché-Escamilla, Gonzalo; Soto-Hernández, Marcos

2015-01-01

In Cactaceae, wood anatomy is related to stem morphology in terms of the conferred support. In species of cacti with dimorphic wood, a unique process occurs in which the cambium stops producing wide-band tracheids (WBTs) and produces fibers; this is associated with the aging of individuals and increases in size. Stem support and lignification have only been studied in fibrous tree-like species, and studies in species with WBTs or dimorphic wood are lacking. In this study, we approach this process with a chemical focus, emphasizing the role of wood lignification. We hypothesized that the degree of wood lignification in Cactaceae increases with height of the species and that its chemical composition varies with wood anatomy. To test this, we studied the chemical composition (cellulose, hemicellulose, and lignin content) in 13 species (2 WBTs wood, 3 dimorphic, and 8 fibrous) with contrasting growth forms. We also analyzed lignification in dimorphic and fibrous species to determine the chemical features of WBTs and fibers and their relationship with stem support. The lignin contents were characterized by Fourier transform infrared spectroscopy and high performance liquid chromatography. We found that 11 species have a higher percentage (>35%) of lignin in their wood than other angiosperms or gymnosperms. The lignin chemical composition in fibrous species is similar to that of other dicots, but it is markedly heterogeneous in non-fibrous species where WBTs are abundant. The lignification in WBTs is associated with the resistance to high water pressure within cells rather than the contribution to mechanical support. Dimorphic wood species are usually richer in syringyl lignin, and tree-like species with lignified rays have more guaiacyl lignin. The results suggest that wood anatomy and lignin distribution play an important role in the chemical composition of wood, and further research is needed at the cellular level. PMID:25880223

Wood chemical composition in species of Cactaceae: the relationship between lignification and stem morphology.

Directory of Open Access Journals (Sweden)

Jorge Reyes-Rivera

Full Text Available In Cactaceae, wood anatomy is related to stem morphology in terms of the conferred support. In species of cacti with dimorphic wood, a unique process occurs in which the cambium stops producing wide-band tracheids (WBTs and produces fibers; this is associated with the aging of individuals and increases in size. Stem support and lignification have only been studied in fibrous tree-like species, and studies in species with WBTs or dimorphic wood are lacking. In this study, we approach this process with a chemical focus, emphasizing the role of wood lignification. We hypothesized that the degree of wood lignification in Cactaceae increases with height of the species and that its chemical composition varies with wood anatomy. To test this, we studied the chemical composition (cellulose, hemicellulose, and lignin content in 13 species (2 WBTs wood, 3 dimorphic, and 8 fibrous with contrasting growth forms. We also analyzed lignification in dimorphic and fibrous species to determine the chemical features of WBTs and fibers and their relationship with stem support. The lignin contents were characterized by Fourier transform infrared spectroscopy and high performance liquid chromatography. We found that 11 species have a higher percentage (>35% of lignin in their wood than other angiosperms or gymnosperms. The lignin chemical composition in fibrous species is similar to that of other dicots, but it is markedly heterogeneous in non-fibrous species where WBTs are abundant. The lignification in WBTs is associated with the resistance to high water pressure within cells rather than the contribution to mechanical support. Dimorphic wood species are usually richer in syringyl lignin, and tree-like species with lignified rays have more guaiacyl lignin. The results suggest that wood anatomy and lignin distribution play an important role in the chemical composition of wood, and further research is needed at the cellular level.

Wood chemical composition in species of Cactaceae: the relationship between lignification and stem morphology.

Science.gov (United States)

Reyes-Rivera, Jorge; Canché-Escamilla, Gonzalo; Soto-Hernández, Marcos; Terrazas, Teresa

2015-01-01

In Cactaceae, wood anatomy is related to stem morphology in terms of the conferred support. In species of cacti with dimorphic wood, a unique process occurs in which the cambium stops producing wide-band tracheids (WBTs) and produces fibers; this is associated with the aging of individuals and increases in size. Stem support and lignification have only been studied in fibrous tree-like species, and studies in species with WBTs or dimorphic wood are lacking. In this study, we approach this process with a chemical focus, emphasizing the role of wood lignification. We hypothesized that the degree of wood lignification in Cactaceae increases with height of the species and that its chemical composition varies with wood anatomy. To test this, we studied the chemical composition (cellulose, hemicellulose, and lignin content) in 13 species (2 WBTs wood, 3 dimorphic, and 8 fibrous) with contrasting growth forms. We also analyzed lignification in dimorphic and fibrous species to determine the chemical features of WBTs and fibers and their relationship with stem support. The lignin contents were characterized by Fourier transform infrared spectroscopy and high performance liquid chromatography. We found that 11 species have a higher percentage (>35%) of lignin in their wood than other angiosperms or gymnosperms. The lignin chemical composition in fibrous species is similar to that of other dicots, but it is markedly heterogeneous in non-fibrous species where WBTs are abundant. The lignification in WBTs is associated with the resistance to high water pressure within cells rather than the contribution to mechanical support. Dimorphic wood species are usually richer in syringyl lignin, and tree-like species with lignified rays have more guaiacyl lignin. The results suggest that wood anatomy and lignin distribution play an important role in the chemical composition of wood, and further research is needed at the cellular level.

Parental response to severe or lethal prenatal diagnosis

DEFF Research Database (Denmark)

Lou, Stina; Jensen, Lotte Groth; Petersen, Olav Bjørn

2017-01-01

Objective A severe or lethal prenatal diagnosis places great demands on prospective parents, who face choices of far-reaching consequences, such as continuing or terminating the pregnancy. How best to support these parents is a clinical challenge. This systematic review aimed to identify and synt......Objective A severe or lethal prenatal diagnosis places great demands on prospective parents, who face choices of far-reaching consequences, such as continuing or terminating the pregnancy. How best to support these parents is a clinical challenge. This systematic review aimed to identify...... and synthesize the qualitative evidence regarding prospective parents’ responses to such prenatal diagnoses. Methods Following PRISMA guidelines, four databases were systematically searched and 28 studies met the inclusion criteria. Thematic analysis guided data extraction and synthesis of findings. The CERQual....... Prospective parents who continued the pregnancy wished to be acknowledged as parents, and engaged in planning to obtain a sense of meaning and control. Selective disclosure and concerns about negative responses were issues both for the parents who terminated and those who continued a pregnancy. Conclusion...

Cell-cycle variation in the induction of lethality and mitotic recombination after treatment with UV and nitrous acid in the yeast, Saccharomyces cerevisiae

International Nuclear Information System (INIS)

Davies, P.J.; Tippins, R.S.; Parry, J.M.

1978-01-01

Exponentially growing yeast cultures separated into discrete periods of the cell cycle by zonal rotor centrifugation show cyclic variation in both UV and nitrous acid induced cell lethality, mitotic gene conversion and mitotic crossing-over. Maximum cell survival after UV treatment was observed in the S and G2 phases of the cell cycle at a time when UV induction of both types of mitotic recombination was at a minumum. In contrast, cell inactivation by the chemical mutagen nitrous acid showed a single discrete period of sensitivity which occurred in S phase cells which are undergoing DNA synthesis. Mitotic gene conversion ahd mitotic crossing-over were induced by nitrous acid in cells at all stages of the cell cycle with a peak of induction of both events occurring at the time of maximum cell lethality. The lack of correlation observed between maximum cell survival and the maximum induction of mitotic intragenic recombination suggest that other DNA-repair mechanisms besides DNA-recombination repair are involved in the recovery of inactivated yeast cells during the cell cycle. (Auth.)

Lethal Effect of Gamma Irradiation on the Potato Tuber Moth, Phthorimaea operculella (Zeller) and its Effect on Certain Physicochemical Properties of Potato Tubers

International Nuclear Information System (INIS)

Aly, G.M.; Rizk, S. A.; Abdalla, R.S.; Sobeiha, A.M.K.; Dahroug, S.M.

2012-01-01

Exposure of 4-day-old eggs of Phthorimaea operculella (Zeller) to a dose level of 800 Gy of gamma radiation caused complete mortality and prevent egg hatching after 4 days from exposure to radiation. This dose level was considered as the lethal dose for the egg stage. The dose levels of 700 and 2800 Gy were considered lethal for the full grown larvae after periods of 9 and 1 days elapsed respectively from exposure to gamma radiation .The percent larval mortality increased with the increase of both the dose level applied and the time elapsed after exposure to gamma radiation. Irradiation of full grown pupae at the dose level 1900 Gy resulted in a complete reduction of adult emergence, reached 100 % . It could be concluded that gamma irradiation with a dose level 2800 Gy caused complete mortality to different stages of Phthorimaea operculella. Moreover, the physical and chemical properties of irradiated potato tubers did not significantly differ as compared to unirradiated tubers .This obtained, fatal irradiation dose did not exceed the safe limits recommended by the international organization FAO/WHO.

Interaction of radiation, Dihydroxyanthraquinone, and Adriamycin on the induction of acute lethality in mice

International Nuclear Information System (INIS)

Kimler, B.F.; Cox, G.G.; Reddy, E.K.

1984-01-01

The acute lethality induced by combinations of radiation, Dihydroxyanthraquinone (DHAQ), and Adriamycin (ADR) was investigated in mice. Whole-body irradiation produced acute lethality, with an LD-50/30 of approximately 6.5 Gy. ADR and DHAQ produced LD-50/30's of 14 and 4 mg/kg, respectively. When 10 mg/kg doses were fractionated into 5 x 2 mg/kg daily doses, both drugs were equally or more efficient at producing mortality, 90% by day 30. When 4 Gy radiation was combined with 5 mg/kg ADR or 5 mg/kg DHAQ, a response no greater than that produced by drug alone was obtained. However, when 5 mg/kg ADR was administered concomitantly with 5 mg/kg DHAQ, there was a less-than-additive induction of lethality, resulting in only 21% mortality by day 20. ADR and DHAQ (at doses of 5 mg/kg) were combined but with a 1 day interval between drugs, the protective effect was lost and animals died earlier than after either agent alone. At present, no definite explanation is available for this unusual protective effect of ADR against acute lethality induced by DHAQ

Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy

OpenAIRE

Kandadi, Machender R; Yu, Xuejun; Frankel, Arthur E; Ren, Jun

2012-01-01

Abstract Background Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Methods Wild type (WT) and cardiac-specific catalase overexpression mice were challenged...

Improved chemical radioprotection following activation with dextran sulfate

International Nuclear Information System (INIS)

Bartonickova, A.; Vacek, A.; Rotkovska, D.

1982-01-01

The radioresistance was observed of mice after sublethal and lethal gamma irradiation following a combined application of dextran sulphate and the chemical radioprotectors cystamine and mexamine. The mechanism of the radioprotection by mexamine and cystamine is connected with their effect on the oxygen tension in tissues. With the application of dextran sulphate an increase was observed in metabolic activity of tissues and a reduced oxygen tension in the medium will result in a deeper cell hypoxia in the tissue. (M.D.)

Recovery from UV-induced potentially lethal damage in systemic lupus erythematosus skin fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Zamansky, G B

1986-08-01

The repair of ultraviolet light-induced potentially lethal damage was investigated in density-inhibited skin fibroblast cell strains derived from patients with systemic lupus erythematosus. The effect of exposure to polychromatic ultraviolet light composed of environmentally relevant wavelengths or to the more commonly studied, short wavelength (254 nm) ultraviolet light was studied. Systemic lupus erythematosus cells, which are hypersensitive to ultraviolet light under growth promoting conditions, were able to repair potentially lethal damage as well as normal cells.

Recovery from UV-induced potentially lethal damage in systemic lupus erythematosus skin fibroblasts

International Nuclear Information System (INIS)

Zamansky, G.B.

1986-01-01

The repair of ultraviolet light-induced potentially lethal damage was investigated in density-inhibited skin fibroblast cell strains derived from patients with systemic lupus erythematosus. The effect of exposure to polychromatic ultraviolet light composed of environmentally relevant wavelengths or to the more commonly studied, short wavelength (254 nm) ultraviolet light was studied. Systemic lupus erythematosus cells, which are hypersensitive to ultraviolet light under growth promoting conditions, were able to repair potentially lethal damage as well as normal cells. (author)

A comparative study of proliferative nodules and lethal melanomas in congenital nevi from children.

Science.gov (United States)

Yélamos, Oriol; Arva, Nicoleta C; Obregon, Roxana; Yazdan, Pedram; Wagner, Annette; Guitart, Joan; Gerami, Pedram

2015-03-01

Differentiating proliferative nodules (PNs) from melanomas arising in congenital nevi (CN) is a considerable challenge for dermatopathologists. Most of the specimens dermatopathologists assess that deal with this differential diagnosis involve proliferations of melanocytes arising in the dermis. In this study, we compare the clinical, histologic, and molecular findings of these 2 conditions. In our database, we found 22 examples of PNs arising in the dermis of CN and 2 cases of lethal melanomas arising from the dermis/epidermis of CN of children. Importantly, we found that among dermal melanocytic proliferations arising from CN in children, PNs are far more common than lethal melanomas. Clinically, multiplicity of lesions favored a diagnosis of PNs, whereas ulceration was infrequent in PNs compared with lethal melanomas. Histologically, PNs showed several distinct patterns including expansile nodules of epithelioid melanocytes with mitotic counts lower than that seen in the melanomas (1.67 vs. 12.5 mitoses/mm), a small round blue cell pattern often highly mitotically active, neurocristic-like, blue nevus-like, a nevoid melanoma-like pattern, or an undifferentiated spindle cell pattern. The lethal melanomas both featured expansile nodules of epithelioid melanocytes with high mitotic counts (range, 5 to 20 mitoses/mm) and an ulcerated overlying epidermis. At the molecular level, the PNs showed mostly whole chromosomal copy number aberrations, which in some cases were accompanied by rare partial chromosomal aberrations, whereas both lethal melanomas showed highly elevated copy number aberrations involving 6p25 without gains of the long arm of chromosome 6.

Caffeine and D2O medium interact in affecting the expression of radiation-induced potentially lethal damage

International Nuclear Information System (INIS)

Utsumi, H.; Elkind, M.M.

1991-01-01

Earlier work has been extended to compare the killing of long-phase V79 Chinese hamster cells by ionizing radiation when they are treated immediately after irradiation with medium containing either caffeine or 90% D 2 O. The object was to determine if the enhanced killing due to post-treatment with caffeine, or D 2 O, resulted from action on the same sector of potentially lethal damage as appeared to be the case for hypertonic shock and D 2 O medium. The treatments by themselves were not toxic to unirradiated cells. We found that the enhanced expression of potentially lethal damage by post-treatment with caffeine or D 2 O medium is similar. For example, the kinetic of the repair of the potentially lethal damage expressible by either post-treatment was similar, and an additive enhancement of potentially lethal damage occurred when the two treatments were administered sequentially. These findings suggest that caffeine and D 2 O medium affect the same sector of potentially lethal damage. When the two treatments were combined, however, they competed with each other. Thus, although caffeine and D 2 O medium act on the same sector of potentially lethal damage they do so differently, suggesting that more than one pathway of the expression of radiation damage can result in the same phenotypic effect. (author)

Fighting Lethal Yellowing Disease for Coconut Farmers (CIFSRF ...

International Development Research Centre (IDRC) Digital Library (Canada)

Copra is the dried kernel of the coconut, which is used to extract coconut oil. Coconut is the main income source for the coastal region's poor farmers. Over the past 10 years, Côte d'Ivoire lethal yellowing disease has destroyed more than 350 hectares of coconut and caused losses of 12,000 tons of copra per year.

Perforated appendicitis presenting as a thigh abscess: A lethal ...

African Journals Online (AJOL)

Typical cases of acute appendicitis have excellent treatment outcomes, if managed appropriately.1 We discuss an unusual case of perforated retrocaecal appendicitis that presented as a right thigh abscess without prominent abdominal symptoms, which highlights the lethal nature of advanced appendicitis even when ...

Metformin is synthetically lethal with glucose withdrawal in cancer cells.

Science.gov (United States)

Menendez, Javier A; Oliveras-Ferraros, Cristina; Cufí, Sílvia; Corominas-Faja, Bruna; Joven, Jorge; Martin-Castillo, Begoña; Vazquez-Martin, Alejandro

2012-08-01

Glucose deprivation is a distinctive feature of the tumor microecosystem caused by the imbalance between poor supply and an extraordinarily high consumption rate. The metabolic reprogramming from mitochondrial respiration to aerobic glycolysis in cancer cells (the "Warburg effect") is linked to oncogenic transformation in a manner that frequently implies the inactivation of metabolic checkpoints such as the energy rheostat AMP-activated protein kinase (AMPK). Because the concept of synthetic lethality in oncology can be applied not only to genetic and epigenetic intrinsic differences between normal and cancer cells but also to extrinsic ones such as altered microenvironment, we recently hypothesized that stress-energy mimickers such as the AMPK agonist metformin should produce metabolic synthetic lethality in a glucose-starved cell culture milieu imitating the adverse tumor growth conditions in vivo. Under standard high-glucose conditions, metformin supplementation mostly caused cell cycle arrest without signs of apoptotic cell death. Under glucose withdrawal stress, metformin supplementation circumvented the ability of oncogenes (e.g., HER2) to protect breast cancer cells from glucose-deprivation apoptosis. Significantly, representative cell models of breast cancer heterogeneity underwent massive apoptosis (by >90% in some cases) when glucose-starved cell cultures were supplemented with metformin. Our current findings may uncover crucial issues regarding the cell-autonomous metformin's anti-cancer actions: (1) The offently claimed clinically irrelevant, non-physiological concentrations needed to observe the metformin's anti-cancer effects in vitro merely underlie the artifactual interference of erroneous glucose-rich experimental conditions that poorly reflect glucose-starved in vivo conditions; (2) the preferential killing of cancer stem cells (CSC) by metformin may simply expose the best-case scenario for its synthetically lethal activity because an increased

Differential replication of Foot-and-mouth disease viruses in mice determine lethality.

Science.gov (United States)

Cacciabue, Marco; García-Núñez, María Soledad; Delgado, Fernando; Currá, Anabella; Marrero, Rubén; Molinari, Paula; Rieder, Elizabeth; Carrillo, Elisa; Gismondi, María Inés

2017-09-01

Adult C57BL/6J mice have been used to study Foot-and-mouth disease virus (FMDV) biology. In this work, two variants of an FMDV A/Arg/01 strain exhibiting differential pathogenicity in adult mice were identified and characterized: a non-lethal virus (A01NL) caused mild signs of disease, whereas a lethal virus (A01L) caused death within 24-48h independently of the dose used. Both viruses caused a systemic infection with pathological changes in the exocrine pancreas. Virus A01L reached higher viral loads in plasma and organs of inoculated mice as well as increased replication in an ovine kidney cell line. Complete consensus sequences revealed 6 non-synonymous changes between A01L and A10NL genomes that might be linked to replication differences, as suggested by in silico prediction studies. Our results highlight the biological significance of discrete genomic variations and reinforce the usefulness of this animal model to study viral determinants of lethality. Copyright © 2017 Elsevier Inc. All rights reserved.

Highly predictive support vector machine (SVM) models for anthrax toxin lethal factor (LF) inhibitors.

Science.gov (United States)

Zhang, Xia; Amin, Elizabeth Ambrose

2016-01-01

Anthrax is a highly lethal, acute infectious disease caused by the rod-shaped, Gram-positive bacterium Bacillus anthracis. The anthrax toxin lethal factor (LF), a zinc metalloprotease secreted by the bacilli, plays a key role in anthrax pathogenesis and is chiefly responsible for anthrax-related toxemia and host death, partly via inactivation of mitogen-activated protein kinase kinase (MAPKK) enzymes and consequent disruption of key cellular signaling pathways. Antibiotics such as fluoroquinolones are capable of clearing the bacilli but have no effect on LF-mediated toxemia; LF itself therefore remains the preferred target for toxin inactivation. However, currently no LF inhibitor is available on the market as a therapeutic, partly due to the insufficiency of existing LF inhibitor scaffolds in terms of efficacy, selectivity, and toxicity. In the current work, we present novel support vector machine (SVM) models with high prediction accuracy that are designed to rapidly identify potential novel, structurally diverse LF inhibitor chemical matter from compound libraries. These SVM models were trained and validated using 508 compounds with published LF biological activity data and 847 inactive compounds deposited in the Pub Chem BioAssay database. One model, M1, demonstrated particularly favorable selectivity toward highly active compounds by correctly predicting 39 (95.12%) out of 41 nanomolar-level LF inhibitors, 46 (93.88%) out of 49 inactives, and 844 (99.65%) out of 847 Pub Chem inactives in external, unbiased test sets. These models are expected to facilitate the prediction of LF inhibitory activity for existing molecules, as well as identification of novel potential LF inhibitors from large datasets. Copyright © 2015 Elsevier Inc. All rights reserved.

Molecular analysis of two mouse dilute locus deletion mutations: Spontaneous dilute lethal20J and radiation-induced dilute prenatal lethal Aa2 alleles

International Nuclear Information System (INIS)

Strobel, M.C.; Seperack, P.K.; Copeland, N.G.; Jenkins, N.A.

1990-01-01

The dilute (d) coat color locus of mouse chromosome 9 has been identified by more than 200 spontaneous and mutagen-induced recessive mutations. With the advent of molecular probes for this locus, the molecular lesion associated with different dilute alleles can be recognized and precisely defined. In this study, two dilute mutations, dilute-lethal20J (dl20J) and dilute prenatal lethal Aa2, have been examined. Using a dilute locus genomic probe in Southern blot analysis, we detected unique restriction fragments in dl20J and Aa2 DNA. Subsequent analysis of these fragments showed that they represented deletion breakpoint fusion fragments. DNA sequence analysis of each mutation-associated deletion breakpoint fusion fragment suggests that both genomic deletions were generated by nonhomologous recombination events. The spontaneous dl20J mutation is caused by an interstitial deletion that removes a single coding exon of the dilute gene. The correlation between this discrete deletion and the expression of all dilute-associated phenotypes in dl20J homozygotes defines the dl20J mutation as a functional null allele of the dilute gene. The radiation-induced Aa2 allele is a multilocus deletion that, by complementation analysis, affects both the dilute locus and the proximal prenatal lethal-3 (pl-3) functional unit. Molecular analysis of the Aa2 deletion breakpoint fusion fragment has provided access to a previously undefined gene proximal to d. Initial characterization of this new gene suggests that it may represent the genetically defined pl-3 functional unit

Models for pulmonary lethality and morbidity after irradiation from internal and external sources

International Nuclear Information System (INIS)

Scott, B.R.; Filipy, R.E.; Hahn, E.F.

1989-05-01

This report provides a hazard-function model for estimating the risk of death from radiation pneumonitis and/or pulmonary fibrosis following a light-water nuclear power accident. A similar model is also provided for estimating the prevalence of respiratory functional morbidity among those that survive death from acute effects. Hazard-function models for lethality and for morbidity were constructed using the cumulative hazard estimator H, which is related to the risk estimator R through the equation R = 1-exp(-H). The estimator H can be calculated using information provided in the report. The method of calculation depends on the exposure scenario. In general, the total normalized dose X for lethality or for morbidity is calculated. For lethality, X = 1 corresponds to a median lethal dose (LD 50 ); for morbidity, X = 1 corresponds to a median effective dose (ED 50 ). H is related to X by the equation H = 1n(2)X/sup V/, where V depends on the type of radiation (or radiations) involved. Contributions to X can arise from each of two main modes of exposure: (1) brief exposure of the lung, at a relatively high dose rate, to mainly external gammas, followed by (2) chronic internal alpha, and/or beta, and/or gamma irradiation of the lung. Equations are provided for calculating the contributions to X from both modes of exposure. 73 refs., 16 figs., 2 tabs

Potentiation of radiation lethality by Topotecan, a Topoisomerase I inhibitor

International Nuclear Information System (INIS)

Lamond, J.P.; Kinsella, T.J.; Boothman, D.A.

1995-01-01

Purpose/Objective: Topotecan is a water soluble Topoisomerase I (Topo I) inhibitor that has demonstrated antineoplastic activity in phase I/II trials of solid tumors (such as non-small cell lung, small cell lung, ovarian, esophageal and head and neck primaries) and leukemias. We sought to determine (1) if Topotecan potentiated the lethal effects of ionizing radiation, and (2) the characteristics of the synergistic effect. Materials and Methods: Human radioresistant melanoma (U1-Mel) and glioma (D54) cells were grown in Dulbecco's modified Eagle's medium (DME) with 10% fetal calf serum (FCS) until confluence-arrest. Cells were x-irradiated (0-700 cGy) and exposed to various Topotecan concentrations (2-100μM), either before (for 4 hours), during, or after (for 4 hours) irradiation. Appropriate controls were also performed. Survival was determined via colony forming assays. Survival curves were normalized to correct for drug cytotoxicities and variations in initial viable cells plated. In another set of experiments, U1-Mel cells were exposed to 10 μM Topotecan either before, during or after 400 cGy, as described above. A modification of the SDS and KCl assay was used to quantify Topo I-DNA complexes via glass fiber filter binding. All experiments were performed at least 7 times in duplicate. Results: Potentiation of radiation lethality was seen in the U1-Mel and D54 cell lines. The synergistic effects were (1) dependent on drug concentration, with lethality enhancement and minimal drug lethality alone in the 2-10 μM range (2) dependent on timing, with synergy present only when the drug was present at the time of, or shortly after irradiation, and (3) irreversible, with inhibition of potential lethal damage repair (PLDR). The dose enhancement ratios (DER) for 4 μM Topotecan in the U1-Mel cells was 1.7 - 2.4, depending on the survival endpoints that were used. The DER for 2 μM Topotecan in D54 cells was 3.0 - 4.0. The U1-Mel cells that were exposed to Topotecan

Comparative study of different sexis mutability: recessive sex-linked and dominant lethals in Drosophila melanogaster

International Nuclear Information System (INIS)

Vatti, K.V.; Dzhaparidze, L.A.; Mamon, L.A.

1980-01-01

The frequency of recessive sex-linked lethal mutations (RSLLM) and those realizing in embryogenesis of dominant lethals, which form in oo- and spermatogenesis of Drosophila and fly productivity under the effect of X-rays and N-nitroso-N methylourea (NMU), is studied. In the case of effect of both mutagens RSLLM form in spermatocytes with higher frequency as compared with oocytes. Dominant lethal mutations (DLM) during irradiation are also often registered in spermatocytes. NMU induces DLM in mitotic male cells with a very high frequency but is not effective during the effect on oocytes. When both mutagens affect males and X-rays affect females, the decrease of productivity is mainly conditioned by DLM. As NMU does not induce DLM in females realizing in embryogenesis but reduces productivity, a later lethal realization connected with their different nature is supposed. Differences in mole and female mutability found in the course of X-ray and NMU effect are discussed in connection with peculiarities of their mitotic cells and the nature of effect of mutagens applied [ru

9 CFR 430.4 - Control of Listeria monocytogenes in post-lethality exposed ready-to-eat products.

Science.gov (United States)

2010-01-01

... post-lethality exposed ready-to-eat products. 430.4 Section 430.4 Animals and Animal Products FOOD... Control of Listeria monocytogenes in post-lethality exposed ready-to-eat products. (a) Listeria... comes into direct contact with a food contact surface which is contaminated with L. monocytogenes. (b...

The role of pH in lethal effect of glucose load malignant cells

International Nuclear Information System (INIS)

Shmakova, N.L.; Yarmonenko, S.P.; Laser, K.; Fomenkova, T.E.; Kozubek, S.; Korogodin, V.I.

1985-01-01

The lethal effect of variuos pH values on Erlich ascites tumour (EAT) calls has been investigated. Different pH values were obtained by means of both glucose load and phosphate buffers. The effect has been investigated by observing cell death in vitro, determining cancerogenity of EAT cells and determining their radiosensitivity. The results of all methods enabled us to conclude that the same values of pH lead to the same effect on EAT cells independently of the way by which the given pH value was reached. The lethal effect markedly increased when the value of pH was lower than 5.6. It is concluded that the basis of the mechanism of glucose load lethal effect is their ''self-acidisation''. The measurement of pH in tumours is proposed as a basic test for determining the suitability of the use of hyperglycemia in clinics and for comparison of the efficiency of various modes of treatment

Myxoma virus M130R is a novel virulence factor required for lethal myxomatosis in rabbits.

Science.gov (United States)

Barrett, John W; Werden, Steven J; Wang, Fuan; McKillop, William M; Jimenez, June; Villeneuve, Danielle; McFadden, Grant; Dekaban, Gregory A

2009-09-01

Myxoma virus (MV) is a highly lethal, rabbit-specific poxvirus that induces a disease called myxomatosis in European rabbits. In an effort to understand the function of predicted immunomodulatory genes we have deleted various viral genes from MV and tested the ability of these knockout viruses to induce lethal myxomatosis. MV encodes a unique 15 kD cytoplasmic protein (M130R) that is expressed late (12h post infection) during infection. M130R is a non-essential gene for MV replication in rabbit, monkey or human cell lines. Construction of a targeted gene knockout virus (vMyx130KO) and infection of susceptible rabbits demonstrate that the M130R knockout virus is attenuated and that loss of M130R expression allows the rabbit host immune system to effectively respond to and control the lethal effects of MV. M130R expression is a bona fide poxviral virulence factor necessary for full and lethal development of myxomatosis.

Relationship between chemical structure of soil organic matter and intra-aggregate pore structure: evidence from X-ray computed micro-tomography

Science.gov (United States)

Kravchenko, Alexandra; Grandy, Stuart A.

2014-05-01

Understanding chemical structure of soil organic matter (SOM) and factors that affect it are vital for gaining understanding of mechanisms of C sequestration by soil. Physical protection of C by adsorption to mineral particles and physical disconnection between C sources and microbial decomposers is now regarded as the key component of soil C sequestration. Both of the processes are greatly influenced by micro-scale structure and distribution of soil pores. However, because SOM chemical structure is typically studied in disturbed (ground and sieved) soil samples the experimental evidence of the relationships between soil pore structure and chemical structure of SOM are still scarce. Our study takes advantage of the X-ray computed micro-tomography (µ-CT) tools that enable non-destructive analysis of pore structure in intact soil samples. The objective of this study is to examine the relationship between SOM chemical structure and pore-characteristics in intact soil macro-aggregates from two contrasting long-term land uses. The two studied land use treatments are a conventionally tilled corn-soybean-wheat rotation treatment and a native succession vegetation treatment removed from agricultural use >20 years ago. The study is located in southwest Michigan, USA, on sandy-loam Typic Hapludalfs. For this study we used soil macro-aggregates 4-6 mm in size collected at 0-15 cm depth. The aggregate size was selected so as both to enable high resolution of µ-CT and to provide sufficient amount of soil for C measurements. X-ray µ-CT scanning was conducted at APS Argonne at a scanning resolution of 14 µm. Two scanned aggregates (1 per treatment) were used in this preliminary study. Each aggregate was cut into 7 "geo-referenced" sections. Analyses of pore characteristics in each section were conducted using 3DMA and ImageJ image analysis tools. SOM chemistry was analyzed using pyrolysis/gas chromatography-mass spectroscopy. Results demonstrated that the relationships

Phleomycin-induced lethality and DNA degradation in Escherichia coli K12

Energy Technology Data Exchange (ETDEWEB)

Nakayama, H

1975-01-01

The cell lethality and DNA fragmentation caused by phleomycin (PM) were studied in E. coli K12 strains with special reference to the effects of repair or recombination deficiencies and metabolic inhibitors. Unlike excision-defective derivatives of E. coli B, uvrA, uvrB, and uvrC mutants of strain K12 showed no peculiarities compared with wild type in regard to cell survival. Likewise, mutant alleles at uvrD and polA loci had no effect. In contrast, rec mutants were more sensitive to PM-killing than were rec/sup +/ strains. PM-induced strand breakage in DNA was observed in all strains tested including the above-mentioned mutants. There was no significant distinction between the uvr mutants and the wild type strain, indicating that the uvr-endonuclease was not responsible for the strand breaks. Involvement of endonuclease I was also ruled out. At least some of the PM-induced strand breaks were repairable. PM-induced lethality and strand breakage were totally dependent on energy supply. Inhibition of protein synthesis resulted in a partial and parallel suppression of the two effects. Our results suggest that the lethality is due to DNA strand breakage and the repair of such damage is postulated to be controlled by rec genes.

Some aspects of chemical ecology of the sponges of the Caribbean, Axinyssa ambrosia and Aplysina insularis

International Nuclear Information System (INIS)

Puyana Monica; Petrichtcheva, Natalia; Morales, Alicia; Duque Carmenza

2002-01-01

Axinyssamine hydrochloride (compound 1) was recently found in the marine sponge Axinyssa ambrosia at concentrations in the order of 10 mg/ml. Lethality assays using compound 1 against the coral Madracis mirabilis allowed determining that the mentioned compound is lethal to coral polyps at the natural concentration present in the sponge. Additionally, by performing exudation experiments in aquaria and chemical detection by HRGC-MS (scan and sim modes) it was found that the compounds ll-formamide-7β-H-eudesm-5-ene (2) and 4 α-formamidogorgon-ll-ene (3) are continually exuded by Axinyssa ambrosia creating a protective chemical barrier around the sponge. Exudation rates increase 3.80 and 2.47 fold respectively for each compound, under stress conditions or aggression. These results suggest that the sponge Axinyssa ambrosia may use the above-mentioned three metabolites as chemical defenses. Other experiments were carried out with the sponge Aplysina insularis in situ, under ecologically relevant conditions, with the purpose of determining if the chemical composition (Brominated metabolites) changes over variable time periods after inflicting wounds on the sponge surface. Metabolites were detected and identified by LC-MS. No evidence of chemical transformation of high molecular weight compounds into the compounds Aeroplysinin-l (4) and/or the dibromo cyclohexadienone (5) was obtained as a consequence of tissue damage, both in short (2,5 minutes) and long duration experiments (120 minutes). These results suggest that the conversion of high molecular weight compounds into small, active forms does not take place in Aplysina insularis as a chemical defense mechanism

The population genetics of X-autosome synthetic lethals and steriles.

Science.gov (United States)

Lachance, Joseph; Johnson, Norman A; True, John R

2011-11-01

Epistatic interactions are widespread, and many of these interactions involve combinations of alleles at different loci that are deleterious when present in the same individual. The average genetic environment of sex-linked genes differs from that of autosomal genes, suggesting that the population genetics of interacting X-linked and autosomal alleles may be complex. Using both analytical theory and computer simulations, we analyzed the evolutionary trajectories and mutation-selection balance conditions for X-autosome synthetic lethals and steriles. Allele frequencies follow a set of fundamental trajectories, and incompatible alleles are able to segregate at much higher frequencies than single-locus expectations. Equilibria exist, and they can involve fixation of either autosomal or X-linked alleles. The exact equilibrium depends on whether synthetic alleles are dominant or recessive and whether fitness effects are seen in males, females, or both sexes. When single-locus fitness effects and synthetic incompatibilities are both present, population dynamics depend on the dominance of alleles and historical contingency (i.e., whether X-linked or autosomal mutations occur first). Recessive synthetic lethality can result in high-frequency X-linked alleles, and dominant synthetic lethality can result in high-frequency autosomal alleles. Many X-autosome incompatibilities in natural populations may be cryptic, appearing to be single-locus effects because one locus is fixed. We also discuss the implications of these findings with respect to standing genetic variation and the origins of Haldane's rule.

Lethal Interpersonal Violence in the Middle Pleistocene

OpenAIRE

Sala, Nohemi; Arsuaga, Juan Luis; Pantoja-P?rez, Ana; Pablos, Adri?n; Mart?nez, Ignacio; Quam, Rolf M.; G?mez-Olivencia, Asier; Berm?dez de Castro, Jos? Mar?a; Carbonell, Eudald

2015-01-01

Evidence of interpersonal violence has been documented previously in Pleistocene members of the genus Homo, but only very rarely has this been posited as the possible manner of death. Here we report the earliest evidence of lethal interpersonal violence in the hominin fossil record. Cranium 17 recovered from the Sima de los Huesos Middle Pleistocene site shows two clear perimortem depression fractures on the frontal bone, interpreted as being produced by two episodes of localized blunt force ...

Identification of Lilial as a fragrance sensitizer in a perfume by bioassay-guided chemical fractionation and structure-activity relationships

DEFF Research Database (Denmark)

Arnau, E G; Andersen, Klaus Ejner; Bruze, M

2000-01-01

Fragrance materials are among the most common causes of allergic contact dermatitis. The aim of this study was to identify in a perfume fragrance allergens not included in the fragrance mix, by use of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships...... (SARs). The basis for the investigation was a 45-year-old woman allergic to her own perfume. She had a negative patch test to the fragrance mix and agreed to participate in the study. Chemical fractionation of the perfume concentrate was used for repeated patch testing and/or repeated open application......" in their chemical structure, indicating an ability to modify skin proteins and thus behave as a skin sensitizer, were tested on the patient. The patient reacted positively to the synthetic fragrance p-t-butyl-alpha-methylhydrocinnamic aldehyde (Lilial), a widely used fragrance compound not present in the fragrance...

Development of System Architecture to Investigate the Impact of Integrated Air and Missile Defense in a Distributed Lethality Environment

Science.gov (United States)

2017-12-01

SYSTEM ARCHITECTURE TO INVESTIGATE THE IMPACT OF INTEGRATED AIR AND MISSILE DEFENSE IN A DISTRIBUTED LETHALITY ENVIRONMENT by Justin K. Davis...TO INVESTIGATE THE IMPACT OF INTEGRATED AIR AND MISSILE DEFENSE IN A DISTRIBUTED LETHALITY ENVIRONMENT 5. FUNDING NUMBERS 6. AUTHOR(S) Justin K...ARCHITECTURE TO INVESTIGATE THE IMPACT OF INTEGRATED AIR AND MISSILE DEFENSE IN A DISTRIBUTED LETHALITY ENVIRONMENT Justin K. Davis Lieutenant

Tityus serrulatus venom--A lethal cocktail.

Science.gov (United States)

Pucca, Manuela Berto; Cerni, Felipe Augusto; Pinheiro Junior, Ernesto Lopes; Bordon, Karla de Castro Figueiredo; Amorim, Fernanda Gobbi; Cordeiro, Francielle Almeida; Longhim, Heloisa Tavoni; Cremonez, Caroline Marroni; Oliveira, Guilherme Honda; Arantes, Eliane Candiani

2015-12-15

Tityus serrulatus (Ts) is the main scorpion species of medical importance in Brazil. Ts venom is composed of several compounds such as mucus, inorganic salts, lipids, amines, nucleotides, enzymes, kallikrein inhibitor, natriuretic peptide, proteins with high molecular mass, peptides, free amino acids and neurotoxins. Neurotoxins are considered the most responsible for the envenoming syndrome due to their pharmacological action on ion channels such as voltage-gated sodium (Nav) and potassium (Kv) channels. The major goal of this review is to present important advances in Ts envenoming research, correlating both the crude Ts venom and isolated toxins with alterations observed in all human systems. The most remarkable event lies in the Ts induced massive releasing of neurotransmitters influencing, directly or indirectly, the entire body. Ts venom proved to extremely affect nervous and muscular systems, to modulate the immune system, to induce cardiac disorders, to cause pulmonary edema, to decrease urinary flow and to alter endocrine, exocrine, reproductive, integumentary, skeletal and digestive functions. Therefore, Ts venom possesses toxins affecting all anatomic systems, making it a lethal cocktail. However, its low lethality may be due to the low venom mass injected, to the different venom compositions, the body characteristics and health conditions of the victim and the local of Ts sting. Furthermore, we also described the different treatments employed during envenoming cases. In particular, throughout the review, an effort will be made to provide information from an extensive documented studies concerning Ts venom in vitro, in animals and in humans (a total of 151 references). Copyright © 2015 Elsevier Ltd. All rights reserved.

Relationship between chemical composition and biological function of Pseudomonas aeruginosa lipopolysaccharide: effect on human neutrophil chemotaxis and oxidative burst

DEFF Research Database (Denmark)

Kharazmi, A; Fomsgaard, A; Conrad, R S

1991-01-01

There are conflicting data on the effect of bacterial lipopolysaccharides (LPS) on the function of human neutrophils. The present study was designed to examine the relationship between chemical composition and the modulatory effect of LPS on human neutrophil function. LPS was extracted from five...

The "Lethal Chamber": Further Evidence of the Euthanasia Option.

Science.gov (United States)

Elks, Martin A.

1993-01-01

Historical discussions of the euthanasia or "lethal chamber" option in relation to people with mental retardation are presented. The paper concludes that eugenic beliefs in the primacy of heredity over environment and the positive role of natural selection may have condoned the poor conditions characteristic of large, segregated institutions and…

Presence of virus neutralizing antibodies in cerebral spinal fluid correlates with non-lethal rabies in dogs.

Directory of Open Access Journals (Sweden)

Clement W Gnanadurai

Full Text Available Rabies is traditionally considered a uniformly fatal disease after onset of clinical manifestations. However, increasing evidence indicates that non-lethal infection as well as recovery from flaccid paralysis and encephalitis occurs in laboratory animals as well as humans.Non-lethal rabies infection in dogs experimentally infected with wild type dog rabies virus (RABV, wt DRV-Mexico correlates with the presence of high level of virus neutralizing antibodies (VNA in the cerebral spinal fluid (CSF and mild immune cell accumulation in the central nervous system (CNS. By contrast, dogs that succumbed to rabies showed only little or no VNA in the serum or in the CSF and severe inflammation in the CNS. Dogs vaccinated with a rabies vaccine showed no clinical signs of rabies and survived challenge with a lethal dose of wild-type DRV. VNA was detected in the serum, but not in the CSF of immunized dogs. Thus the presence of VNA is critical for inhibiting virus spread within the CNS and eventually clearing the virus from the CNS.Non-lethal infection with wt RABV correlates with the presence of VNA in the CNS. Therefore production of VNA within the CNS or invasion of VNA from the periphery into the CNS via compromised blood-brain barrier is important for clearing the virus infection from CNS, thereby preventing an otherwise lethal rabies virus infection.

The frequency of allelic lethals and complementation maps in natural populations of drosophila melanogaster from Mexico

Directory of Open Access Journals (Sweden)

Salceda Victor M.

2004-01-01

Full Text Available Departing from a previous study on the genetic loads affecting the second chromosome of Drosophila melanogaster in four natural populations, 171 lethal chromosomes were recovered and maintained as a balanced stocks in the condition Cy L / 1 (l=lethal; of those lethais 24 correspond to population A, 50 to populations B and C and 47 to population D. later on an intra-population allelism test for the four populations was performed for each one. A total of 3807 inter lethal crosses were done yielding a total of i 10 allelic combinations, from them the respective percentage of allelism for each population was calculated and they are as follow: 3.98 % for population A, 1.80 % for population B, 3.67 % for population C and 2.96 % for population D. the observed values for the frequency of allelism in these populations are not significantly different from those reported by other authors in similar studies in natural and/or experimental populations. Beside these values the frequency for singles, doubles, triplets and even quadruplets present in each population were determined, they shown the presence of various complementation maps due to the clustering of few different lethals: also a large complementation map formed by a large cluster involving the presence of 26 different lethals found in population D all of them combined constituting a single unit was found.

Therapeutic efficacy of antibodies lacking Fcγ receptor binding against lethal dengue virus infection is due to neutralizing potency and blocking of enhancing antibodies [corrected].

Directory of Open Access Journals (Sweden)

Katherine L Williams

2013-02-01

Full Text Available Dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS are life-threatening complications following infection with one of the four serotypes of dengue virus (DENV. At present, no vaccine or antiviral therapies are available against dengue. Here, we characterized a panel of eight human or mouse-human chimeric monoclonal antibodies (MAbs and their modified variants lacking effector function and dissected the mechanism by which some protect against antibody-enhanced lethal DENV infection. We found that neutralizing modified MAbs that recognize the fusion loop or the A strand epitopes on domains II and III of the envelope protein, respectively, act therapeutically by competing with and/or displacing enhancing antibodies. By analyzing these relationships, we developed a novel in vitro suppression-of-enhancement assay that predicts the ability of modified MAbs to act therapeutically against antibody-enhanced disease in vivo. These studies provide new insight into the biology of DENV pathogenesis and the requirements for antibodies to treat lethal DENV disease.

Direct measurement of the lethal isotherm for radiofrequency ablation of myocardial tissue.

Science.gov (United States)

Wood, Mark; Goldberg, Scott; Lau, Melissa; Goel, Aneesh; Alexander, Daniel; Han, Frederick; Feinstein, Shawn

2011-06-01

The lethal isotherm for radiofrequency catheter ablation of cardiac myocardium is widely accepted to be 50°C, but this has not been directly measured. The purpose of this study was to directly measure the tissue temperature at the edge of radiofrequency lesions in real time using infrared thermal imaging. Fifteen radiofrequency lesions of 6 to 240 seconds in duration were applied to the left ventricular surface of isolated perfused pig hearts. At the end of radiofrequency delivery, a thermal image of the tissue surface was acquired with an infrared camera. The lesion was then stained and an optical image of the lesion was obtained. The thermal and optical images were electronically merged to allow determination of the tissue temperature at the edge of the lesion at the end of radiofrequency delivery. By adjusting the temperature overlay display to conform with the edge of the radiofrequency lesion, the lethal isotherm was measured to be 60.6°C (interquartile ranges, 59.7° to 62.4°C; range, 58.1° to 64.2°C). The areas encompassed by the lesion border in the optical image and the lethal isotherm in the thermal image were statistically similar and highly correlated (Spearman ρ=0.99, Pradiofrequency delivery or to lesion size (both P>0.64). The areas circumscribed by 50°C isotherms were significantly larger than the areas of the lesions on optical imaging (P=0.002). By direct measurement, the lethal isotherm for cardiac myocardium is near 61°C for radiofrequency energy deliveries radiofrequency ablation is important to clinical practice as well as mathematical modeling of radiofrequency lesions.

Soluble factor(s) from bone marrow cells can rescue lethally irradiated mice by protecting endogenous hematopoietic stem cells.

Science.gov (United States)

Zhao, Yi; Zhan, Yuxia; Burke, Kathleen A; Anderson, W French

2005-04-01

Ionizing radiation-induced myeloablation can be rescued via bone marrow transplantation (BMT) or administration of cytokines if given within 2 hours after radiation exposure. There is no evidence for the existence of soluble factors that can rescue an animal after a lethal dose of radiation when administered several hours postradiation. We established a system that could test the possibility for the existence of soluble factors that could be used more than 2 hours postirradiation to rescue animals. Animals with an implanted TheraCyte immunoisolation device (TID) received lethal-dose radiation and then normal bone marrow Lin- cells were loaded into the device (thereby preventing direct interaction between donor and recipient cells). Animal survival was evaluated and stem cell activity was tested with secondary bone marrow transplantation and flow cytometry analysis. Donor cell gene expression of five antiapoptotic cytokines was examined. Bone marrow Lin- cells rescued lethally irradiated animals via soluble factor(s). Bone marrow cells from the rescued animals can rescue and repopulate secondary lethally irradiated animals. Within the first 6 hours post-lethal-dose radiation, there is no significant change of gene expression of the known radioprotective factors TPO, SCF, IL-3, Flt-3 ligand, and SDF-1. Hematopoietic stem cells can be protected in lethally irradiated animals by soluble factors produced by bone marrow Lin- cells.

Caffeine and D sub 2 O medium interact in affecting the expression of radiation-induced potentially lethal damage

Energy Technology Data Exchange (ETDEWEB)

Utsumi, H. (Kyoto Univ. (Japan). Radiation Biology Center); Elkind, M.M. (Colorado State Univ., Fort Collins, CO (United States). Dept. of Radiological Health Sciences)

1991-10-01

Earlier work has been extended to compare the killing of long-phase V79 Chinese hamster cells by ionizing radiation when they are treated immediately after irradiation with medium containing either caffeine or 90% D{sub 2}O. The object was to determine if the enhanced killing due to post-treatment with caffeine, or D{sub 2}O, resulted from action on the same sector of potentially lethal damage as appeared to be the case for hypertonic shock and D{sub 2}O medium. The treatments by themselves were not toxic to unirradiated cells. We found that the enhanced expression of potentially lethal damage by post-treatment with caffeine or D{sub 2}O medium is similar. For example, the kinetic of the repair of the potentially lethal damage expressible by either post-treatment was similar, and an additive enhancement of potentially lethal damage occurred when the two treatments were administered sequentially. These findings suggest that caffeine and D{sub 2}O medium affect the same sector of potentially lethal damage. When the two treatments were combined, however, they competed with each other. Thus, although caffeine and D{sub 2}O medium act on the same sector of potentially lethal damage they do so differently, suggesting that more than one pathway of the expression of radiation damage can result in the same phenotypic effect. (author).

What Are Reasons for the Large Gender Differences in the Lethality of Suicidal Acts? An Epidemiological Analysis in Four European Countries.

Science.gov (United States)

Mergl, Roland; Koburger, Nicole; Heinrichs, Katherina; Székely, András; Tóth, Mónika Ditta; Coyne, James; Quintão, Sónia; Arensman, Ella; Coffey, Claire; Maxwell, Margaret; Värnik, Airi; van Audenhove, Chantal; McDaid, David; Sarchiapone, Marco; Schmidtke, Armin; Genz, Axel; Gusmão, Ricardo; Hegerl, Ulrich

2015-01-01

In Europe, men have lower rates of attempted suicide compared to women and at the same time a higher rate of completed suicides, indicating major gender differences in lethality of suicidal behaviour. The aim of this study was to analyse the extent to which these gender differences in lethality can be explained by factors such as choice of more lethal methods or lethality differences within the same suicide method or age. In addition, we explored gender differences in the intentionality of suicide attempts. Methods. Design: Epidemiological study using a combination of self-report and official data. Setting: Mental health care services in four European countries: Germany, Hungary, Ireland, and Portugal. Data basis: Completed suicides derived from official statistics for each country (767 acts, 74.4% male) and assessed suicide attempts excluding habitual intentional self-harm (8,175 acts, 43.2% male). Main Outcome Measures and Data Analysis. We collected data on suicidal acts in eight regions of four European countries participating in the EU-funded "OSPI-Europe"-project (www.ospi-europe.com). We calculated method-specific lethality using the number of completed suicides per method * 100 / (number of completed suicides per method + number of attempted suicides per method). We tested gender differences in the distribution of suicidal acts for significance by using the χ2-test for two-by-two tables. We assessed the effect sizes with phi coefficients (φ). We identified predictors of lethality with a binary logistic regression analysis. Poisson regression analysis examined the contribution of choice of methods and method-specific lethality to gender differences in the lethality of suicidal acts. Suicidal acts (fatal and non-fatal) were 3.4 times more lethal in men than in women (lethality 13.91% (regarding 4106 suicidal acts) versus 4.05% (regarding 4836 suicidal acts)), the difference being significant for the methods hanging, jumping, moving objects, sharp objects

Daily ingestion of the probiotic Lactobacillus paracasei ST11 decreases Vaccinia virus dissemination and lethality in a mouse model.

Science.gov (United States)

Dos Santos Pereira Andrade, A C; Lima, M Teixeira; Oliveira, G Pereira; Calixto, R Silva; de Sales E Souza, É Lorenna; da Glória de Souza, D; de Almeida Leite, C M; Ferreira, J M Siqueira; Kroon, E G; de Oliveira, D Bretas; Dos Santos Martins, F; Abrahão, J S

2017-02-07

Vaccinia virus (VACV) is an important pathogen. Although studies have shown relationships between probiotics and viruses, the effect of probiotics on VACV infection is unknown. Therefore, this work aims to investigate the probiotics effects on VACV infection. Mice were divided into four groups, two non-infected groups, one receiving the probiotic, the other one not receiving it, and two groups infected intranasally with VACV Western Reserve (VACV-WR) receiving or not receiving the probiotic. Viral titres in organs and cytokine production in the lungs were analysed. Lung samples were also subjected to histological analysis. The intake of probiotic results in reduction in viral spread with a significant decrease of VACV titer on lung, liver and brain of treated group. In addition,treatment with the probiotic results in attenuated mice lung inflammation showing fewer lesions on histological findings and decreased lethality in mice infected with VACV. The ingestion of Lactobacillus paracasei ST11 (LPST11) after VACV infection resulted in 2/9 animal lethality compared with 4/9 in the VACV group. This is the first study on probiotics and VACV interactions, providing not only information about this interaction, but also proposing a model for future studies involving probiotics and other poxvirus.

Genetic interaction motif finding by expectation maximization – a novel statistical model for inferring gene modules from synthetic lethality

Directory of Open Access Journals (Sweden)

Ye Ping

2005-12-01

Full Text Available Abstract Background Synthetic lethality experiments identify pairs of genes with complementary function. More direct functional associations (for example greater probability of membership in a single protein complex may be inferred between genes that share synthetic lethal interaction partners than genes that are directly synthetic lethal. Probabilistic algorithms that identify gene modules based on motif discovery are highly appropriate for the analysis of synthetic lethal genetic interaction data and have great potential in integrative analysis of heterogeneous datasets. Results We have developed Genetic Interaction Motif Finding (GIMF, an algorithm for unsupervised motif discovery from synthetic lethal interaction data. Interaction motifs are characterized by position weight matrices and optimized through expectation maximization. Given a seed gene, GIMF performs a nonlinear transform on the input genetic interaction data and automatically assigns genes to the motif or non-motif category. We demonstrate the capacity to extract known and novel pathways for Saccharomyces cerevisiae (budding yeast. Annotations suggested for several uncharacterized genes are supported by recent experimental evidence. GIMF is efficient in computation, requires no training and automatically down-weights promiscuous genes with high degrees. Conclusion GIMF effectively identifies pathways from synthetic lethality data with several unique features. It is mostly suitable for building gene modules around seed genes. Optimal choice of one single model parameter allows construction of gene networks with different levels of confidence. The impact of hub genes the generic probabilistic framework of GIMF may be used to group other types of biological entities such as proteins based on stochastic motifs. Analysis of the strongest motifs discovered by the algorithm indicates that synthetic lethal interactions are depleted between genes within a motif, suggesting that synthetic

Restoring efficiency of hemopoietic cell transplantation in a mouse lethally irradiated by a total exposure to X rays

International Nuclear Information System (INIS)

Doria, Gino

1959-10-01

This research thesis reports the study of possibility of treatments (or restoration) of a mouse which has been submitted to a lethal dose of X rays. More particularly, the author compared the restoring efficiency of bone marrow and fetal liver injected in a mouse which had been lethally irradiated by a total exposure to X rays. He also studied the functional status of the hemopoietic graft, and the emergence of the secondary disease in mice which had been as well lethally irradiated and then restored by injection of bone marrow and fetal liver. The author then addressed the influence of the induction of immune tolerance of the host with respect to the donor on the survival of a mouse lethally irradiated and restored by homologue bone marrow [fr

Development of polyparameter linear free energy relationship models for octanol-air partition coefficients of diverse chemicals.

Science.gov (United States)

Jin, Xiaochen; Fu, Zhiqiang; Li, Xuehua; Chen, Jingwen

2017-03-22

The octanol-air partition coefficient (K OA ) is a key parameter describing the partition behavior of organic chemicals between air and environmental organic phases. As the experimental determination of K OA is costly, time-consuming and sometimes limited by the availability of authentic chemical standards for the compounds to be determined, it becomes necessary to develop credible predictive models for K OA . In this study, a polyparameter linear free energy relationship (pp-LFER) model for predicting K OA at 298.15 K and a novel model incorporating pp-LFERs with temperature (pp-LFER-T model) were developed from 795 log K OA values for 367 chemicals at different temperatures (263.15-323.15 K), and were evaluated with the OECD guidelines on QSAR model validation and applicability domain description. Statistical results show that both models are well-fitted, robust and have good predictive capabilities. Particularly, the pp-LFER model shows a strong predictive ability for polyfluoroalkyl substances and organosilicon compounds, and the pp-LFER-T model maintains a high predictive accuracy within a wide temperature range (263.15-323.15 K).

Effects of radiation and other influences on chemical lymphomagenesis

Energy Technology Data Exchange (ETDEWEB)

Seidel, H.J.

1987-06-01

Methylnitrosourea (MNU) or butylnitrosourea (BNU) was used to induce T cell lymphomas (thymomas) in BDF/sub 1/ mice. In addition to the chemical, X-rays in various dose schedules were applied. An effect of the irradiation (shortening of the latency period) was seen with 12 x 0.25 Gy in protocols with a prolonged median induction time in the controls as a result of a dose reduction of the chemical (median induction time 27-36 weeks instead of 16-18 weeks under optimal conditions using 50 mg kg/sup -1/ of MNU). Preirradiation 2-5 weeks before 40 mg kg/sup -1/ of MNU resulted in enhanced leukaemogenesis. Also, mice with regenerating lympho-haemopoiesis after lethal irradiation and bone marrow transplantation were more sensitive to the effect of both chemicals than were the controls. Treatment with anti-thy 1.2 and with corynebacterium parvum during the latency period had no influence.

What Are Reasons for the Large Gender Differences in the Lethality of Suicidal Acts? An Epidemiological Analysis in Four European Countries.

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Roland Mergl

Full Text Available In Europe, men have lower rates of attempted suicide compared to women and at the same time a higher rate of completed suicides, indicating major gender differences in lethality of suicidal behaviour. The aim of this study was to analyse the extent to which these gender differences in lethality can be explained by factors such as choice of more lethal methods or lethality differences within the same suicide method or age. In addition, we explored gender differences in the intentionality of suicide attempts.Methods. Design: Epidemiological study using a combination of self-report and official data. Setting: Mental health care services in four European countries: Germany, Hungary, Ireland, and Portugal. Data basis: Completed suicides derived from official statistics for each country (767 acts, 74.4% male and assessed suicide attempts excluding habitual intentional self-harm (8,175 acts, 43.2% male. Main Outcome Measures and Data Analysis. We collected data on suicidal acts in eight regions of four European countries participating in the EU-funded "OSPI-Europe"-project (www.ospi-europe.com. We calculated method-specific lethality using the number of completed suicides per method * 100 / (number of completed suicides per method + number of attempted suicides per method. We tested gender differences in the distribution of suicidal acts for significance by using the χ2-test for two-by-two tables. We assessed the effect sizes with phi coefficients (φ. We identified predictors of lethality with a binary logistic regression analysis. Poisson regression analysis examined the contribution of choice of methods and method-specific lethality to gender differences in the lethality of suicidal acts.Suicidal acts (fatal and non-fatal were 3.4 times more lethal in men than in women (lethality 13.91% (regarding 4106 suicidal acts versus 4.05% (regarding 4836 suicidal acts, the difference being significant for the methods hanging, jumping, moving objects, sharp

Immune Protection against Lethal Fungal-Bacterial Intra-Abdominal Infections

Science.gov (United States)

Lilly, Elizabeth A.; Ikeh, Melanie; Nash, Evelyn E.; Fidel, Paul L.

2018-01-01

ABSTRACT Polymicrobial intra-abdominal infections (IAIs) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation with Candida albicans or other virulent non-albicans Candida (NAC) species plus Staphylococcus aureus resulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis). Surprisingly, inoculation with Candida dubliniensis or Candida glabrata with S. aureus resulted in minimal mortality, and rechallenge of these mice with lethal C. albicans/S. aureus (i.e., coninfection) resulted in >90% protection. The purpose of this study was to define requirements for C. dubliniensis/S. aureus-mediated protection and interrogate the mechanism of the protective response. Protection was conferred by C. dubliniensis alone or by killed C. dubliniensis plus live S. aureus. S. aureus alone was not protective, and killed S. aureus compromised C. dubliniensis-induced protection. C. dubliniensis/S. aureus also protected against lethal challenge by NAC plus S. aureus and could protect for a long-term duration (60 days between primary challenge and C. albicans/S. aureus rechallenge). Unexpectedly, mice deficient in T and B cells (Rag-1 knockouts [KO]) survived both the initial C. dubliniensis/S. aureus challenge and the C. albicans/S. aureus rechallenge, indicating that adaptive immunity did not play a role. Similarly, mice depleted of macrophages prior to rechallenge were also protected. In contrast, protection was associated with high numbers of Gr-1hi polymorphonuclear leukocytes (PMNLs) in peritoneal lavage fluid within 4 h of rechallenge, and in vivo depletion of Gr-1+ cells prior to rechallenge abrogated protection. These results suggest that Candida species can induce protection against a lethal C. albicans/S. aureus IAI that is mediated by PMNLs and postulated to be a unique form of

Immune Protection against Lethal Fungal-Bacterial Intra-Abdominal Infections

Directory of Open Access Journals (Sweden)

Elizabeth A. Lilly

2018-01-01

Full Text Available Polymicrobial intra-abdominal infections (IAIs are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation with Candida albicans or other virulent non-albicans Candida (NAC species plus Staphylococcus aureus resulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis. Surprisingly, inoculation with Candida dubliniensis or Candida glabrata with S. aureus resulted in minimal mortality, and rechallenge of these mice with lethal C. albicans/S. aureus (i.e., coninfection resulted in >90% protection. The purpose of this study was to define requirements for C. dubliniensis/S. aureus-mediated protection and interrogate the mechanism of the protective response. Protection was conferred by C. dubliniensis alone or by killed C. dubliniensis plus live S. aureus. S. aureus alone was not protective, and killed S. aureus compromised C. dubliniensis-induced protection. C. dubliniensis/S. aureus also protected against lethal challenge by NAC plus S. aureus and could protect for a long-term duration (60 days between primary challenge and C. albicans/S. aureus rechallenge. Unexpectedly, mice deficient in T and B cells (Rag-1 knockouts [KO] survived both the initial C. dubliniensis/S. aureus challenge and the C. albicans/S. aureus rechallenge, indicating that adaptive immunity did not play a role. Similarly, mice depleted of macrophages prior to rechallenge were also protected. In contrast, protection was associated with high numbers of Gr-1hi polymorphonuclear leukocytes (PMNLs in peritoneal lavage fluid within 4 h of rechallenge, and in vivo depletion of Gr-1+ cells prior to rechallenge abrogated protection. These results suggest that Candida species can induce protection against a lethal C. albicans/S. aureus IAI that is mediated by PMNLs and postulated to be a unique form of

Generalized concept of the LET-RBE relationship of radiation-induced chromosome aberration and cell death

International Nuclear Information System (INIS)

Takatsuji, Toshihiro; Yoshikawa, Isao; Sasaki, Masao S.

1999-01-01

The frequency of chromosome aberrations per traversal of a nucleus by a charged particle at the low dose limit increases proportionally to the square of the linear energy transfer (LET), peaks at about 100 keV/μm and then decreases with further increase of LET. This has long been interpreted as an excessive energy deposition over the necessary energy required to produce a biologically effective event. Here, we present an alternative interpretation. Cell traversed by a charged particle has certain probability to receive lethal damage leading to direct death. Such events may increase with an increase of LET and the number of charged particles traversing the cell. Assuming that the lethal damage is distributed according to a Poisson distribution, the probability that a cell has no such damage is expressed by e -cLx , where c is a constant, L is LET, and x is the number of charged particles traversing the cell. From these assumptions, the frequency of chromosome aberration in surviving cells can be described by Y=αSD+βS 2 D 2 with the empirical relation Y=αD+βD 2 in the low LET region, where S=e -cL , α is a value proportional to LET, β is a constant, and D is the absorbed dose. This model readily explains the empirically established relationship between LET and relative biological effectiveness (RBE). The model can also be applied to clonogenic survival. If cells can survive and they have neither unstable chromosome aberrations nor other lethal damage, the LET-RBE relationship for clonogenic survival forms a humped curve. The relationship between LET and inactivation cross-section becomes proportional to the square of LET in the low LET region when the frequency of a directly lethal events is sufficiently smaller than unity, and the inactivation cross-section saturates to the cell nucleus cross-sectional area with an increase in LET in the high LET region. (author)

Discovery and Development of Therapeutic Drugs against Lethal Human RNA Viruses: a Multidisciplinary Assault.

Science.gov (United States)

1991-07-16

AD-A239 742 AD GRANT NO: DAMD17-89-Z-9021 TITLE: DISCOVERY AND DEVELOPMENT OF THERAPEUTIC DRUGS AGAINST LETHAL HUMAN RNA VIRUSES: A MULTIDISCIPLINARY...62787A871 AB WrJDA317987 11. TITLE (Include Securty Classification) DISCOVERY AND DEVELOPMENT OF THERAPEUTIC DRUGS AGAINST LETHAL HUMAN RNA VIRUSES: A...G. R. Pettit, III, D.-S. Huang, and G. R. Pettit, 23rd Int’l. Horticulture Congress, Italy, 8/27 - 9/1/90. "Bryostatins Define the Role of Protein

Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge

Science.gov (United States)

Konduru, Krishnamurthy; Shurtleff, Amy C.; Bradfute, Steven B.; Nakamura, Siham; Bavari, Sina; Kaplan, Gerardo

2016-01-01

Ebola virus (EBOV), a member of the Filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. Currently, there are no licensed vaccines or therapeutics to prevent and treat EBOV infection. Several vaccines based on the EBOV glycoprotein (GP) are under development, including vectored, virus-like particles, and protein-based subunit vaccines. We previously demonstrated that a subunit vaccine containing the extracellular domain of the Ebola ebolavirus (EBOV) GP fused to the Fc fragment of human IgG1 (EBOVgp-Fc) protected mice against EBOV lethal challenge. Here, we show that the EBOVgp-Fc vaccine formulated with QS-21, alum, or polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) adjuvants induced strong humoral immune responses in guinea pigs. The vaccinated animals developed anti-GP total antibody titers of approximately 105−106 and neutralizing antibody titers of approximately 103 as assessed by a BSL-2 neutralization assay based on vesicular stomatitis virus (VSV) pseudotypes. The poly-ICLC formulated EBOVgp-Fc vaccine protected all the guinea pigs against EBOV lethal challenge performed under BSL-4 conditions whereas the same vaccine formulated with QS-21 or alum only induced partial protection. Vaccination with a mucin-deleted EBOVgp-Fc construct formulated with QS-21 adjuvant did not have a significant effect in anti-GP antibody levels and protection against EBOV lethal challenge compared to the full-length GP construct. The bulk of the humoral response induced by the EBOVgp-Fc vaccine was directed against epitopes outside the EBOV mucin region. Our findings indicate that different adjuvants can eliciting varying levels of protection against lethal EBOV challenge in guinea pigs vaccinated with EBOVgp-Fc, and suggest that levels of total anti-GP antibodies elicit by protein-based GP subunit vaccines do not correlate with protection. Our data further support

Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge.

Science.gov (United States)

Konduru, Krishnamurthy; Shurtleff, Amy C; Bradfute, Steven B; Nakamura, Siham; Bavari, Sina; Kaplan, Gerardo

2016-01-01

Ebola virus (EBOV), a member of the Filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. Currently, there are no licensed vaccines or therapeutics to prevent and treat EBOV infection. Several vaccines based on the EBOV glycoprotein (GP) are under development, including vectored, virus-like particles, and protein-based subunit vaccines. We previously demonstrated that a subunit vaccine containing the extracellular domain of the Ebola ebolavirus (EBOV) GP fused to the Fc fragment of human IgG1 (EBOVgp-Fc) protected mice against EBOV lethal challenge. Here, we show that the EBOVgp-Fc vaccine formulated with QS-21, alum, or polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) adjuvants induced strong humoral immune responses in guinea pigs. The vaccinated animals developed anti-GP total antibody titers of approximately 105-106 and neutralizing antibody titers of approximately 103 as assessed by a BSL-2 neutralization assay based on vesicular stomatitis virus (VSV) pseudotypes. The poly-ICLC formulated EBOVgp-Fc vaccine protected all the guinea pigs against EBOV lethal challenge performed under BSL-4 conditions whereas the same vaccine formulated with QS-21 or alum only induced partial protection. Vaccination with a mucin-deleted EBOVgp-Fc construct formulated with QS-21 adjuvant did not have a significant effect in anti-GP antibody levels and protection against EBOV lethal challenge compared to the full-length GP construct. The bulk of the humoral response induced by the EBOVgp-Fc vaccine was directed against epitopes outside the EBOV mucin region. Our findings indicate that different adjuvants can eliciting varying levels of protection against lethal EBOV challenge in guinea pigs vaccinated with EBOVgp-Fc, and suggest that levels of total anti-GP antibodies elicit by protein-based GP subunit vaccines do not correlate with protection. Our data further support

Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge.

Directory of Open Access Journals (Sweden)

Krishnamurthy Konduru

Full Text Available Ebola virus (EBOV, a member of the Filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. Currently, there are no licensed vaccines or therapeutics to prevent and treat EBOV infection. Several vaccines based on the EBOV glycoprotein (GP are under development, including vectored, virus-like particles, and protein-based subunit vaccines. We previously demonstrated that a subunit vaccine containing the extracellular domain of the Ebola ebolavirus (EBOV GP fused to the Fc fragment of human IgG1 (EBOVgp-Fc protected mice against EBOV lethal challenge. Here, we show that the EBOVgp-Fc vaccine formulated with QS-21, alum, or polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC adjuvants induced strong humoral immune responses in guinea pigs. The vaccinated animals developed anti-GP total antibody titers of approximately 105-106 and neutralizing antibody titers of approximately 103 as assessed by a BSL-2 neutralization assay based on vesicular stomatitis virus (VSV pseudotypes. The poly-ICLC formulated EBOVgp-Fc vaccine protected all the guinea pigs against EBOV lethal challenge performed under BSL-4 conditions whereas the same vaccine formulated with QS-21 or alum only induced partial protection. Vaccination with a mucin-deleted EBOVgp-Fc construct formulated with QS-21 adjuvant did not have a significant effect in anti-GP antibody levels and protection against EBOV lethal challenge compared to the full-length GP construct. The bulk of the humoral response induced by the EBOVgp-Fc vaccine was directed against epitopes outside the EBOV mucin region. Our findings indicate that different adjuvants can eliciting varying levels of protection against lethal EBOV challenge in guinea pigs vaccinated with EBOVgp-Fc, and suggest that levels of total anti-GP antibodies elicit by protein-based GP subunit vaccines do not correlate with protection. Our data

Effects of β-arabinofuranosyladenine on the growth and repair of potentially lethal damage in Ehrlich ascites tumor cells

International Nuclear Information System (INIS)

Iliakis, G.

1980-01-01

β-D-Arabinofuranosyladenine (β-araA) inhibit the growth of Ehrlich ascites tumor cells by selective inhibition of DNA polymerases. RNA and protein synthesis are not significantly affected. Addition of β-araA to the cells after irradiation resulted in a concentration-dependent decrease in survival, presumably due to the inhibition of the repair of potentially lethal damage. Since β-araA selectively inhibits DNA polymerases it is suggested that repair of potentially lethal damage involves steps at the DNA level which require some polymerization. These repair steps take place in the DNA with a velocity comparable to that of the repair of potentially lethal damage. The inhibition of the repair of potentially lethal damage by β-araA was modified by the addition of deoxyadenosine; this supports the finding that β-araA acts competitively against dATP at the molecular level. The inhibition of the repair of potentially lethal damage by β-araA, which is partly reversible, resulted in a concentration-dependent modification of the survival curve. At low concentrations of β-araA a dose-modifying decrease in survival was observed. At higher concentrations (more than 12 μM) the decrease in survival resulted in a decrease of the shoulder width of the survival curve. Eventually an exponential curve was obtained. We suggest therefore that the shoulder of the survival curve results from some repair or potentially lethal damage. Preliminary information has been obtained on the time course of this repair

Lethal infection thresholds of Paenibacillus larvae for honeybee drone and worker larvae (Apis mellifera).

Science.gov (United States)

Behrens, Dieter; Forsgren, Eva; Fries, Ingemar; Moritz, Robin F A

2010-10-01

We compared the mortality of honeybee (Apis mellifera) drone and worker larvae from a single queen under controlled in vitro conditions following infection with Paenibacillus larvae, a bacterium causing the brood disease American Foulbrood (AFB). We also determined absolute P. larvae cell numbers and lethal titres in deceased individuals of both sexes up to 8 days post infection using quantitative real-time PCR (qPCR). Our results show that in drones the onset of infection induced mortality is delayed by 1 day, the cumulative mortality is reduced by 10% and P. larvae cell numbers are higher than in worker larvae. Since differences in bacterial cell titres between sexes can be explained by differences in body size, larval size appears to be a key parameter for a lethal threshold in AFB tolerance. Both means and variances for lethal thresholds are similar for drone and worker larvae suggesting that drone resistance phenotypes resemble those of related workers. © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.

Acute lethality data for Ontario's electric power generation sector effluents covering the period from December 1990 to May 1991

International Nuclear Information System (INIS)

Poirier, D.G.; Lee, J.T.; Mueller, M.C.; Westlake, G.F.

1995-01-01

Regulations require that electric power generation facilities monitor their liquid effluents. Acute lethality tests are simple, rapid standard methods for measuring potential impacts on aquatic ecosystems. These toxicity tests will detect harmful concentrations of chemicals and mixtures of compounds in effluents, but compliance with end of pipe limits for acute toxicity will not necessarily control all adverse environmental effects. In these tests, aquatic organisms were exposed to undiluted effluent, as well as a series of effluent dilutions for a fixed period of time. This report is a compilation of six months of test results. Typically the most toxic samples were taken from the waste treatment plant (WTP) neutral sumps. This was true for fossil fueled as well as for nuclear generating stations. tabs., figs

An Immature Myeloid/Myeloid-Suppressor Cell Response Associated with Necrotizing Inflammation Mediates Lethal Pulmonary Tularemia.

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Sivakumar Periasamy

2016-03-01

Full Text Available Inhalation of Francisella tularensis (Ft causes acute and fatal pneumonia. The lung cytokine milieu favors exponential Ft replication, but the mechanisms underlying acute pathogenesis and death remain unknown. Evaluation of the sequential and systemic host immune response in pulmonary tularemia reveals that in contrast to overwhelming bacterial burden or cytokine production, an overt innate cellular response to Ft drives tissue pathology and host mortality. Lethal infection with Ft elicits medullary and extra-medullary myelopoiesis supporting recruitment of large numbers of immature myeloid cells and MDSC to the lungs. These cells fail to mature and die, leading to subsequent necrotic lung damage, loss of pulmonary function, and host death that is partially dependent upon immature Ly6G+ cells. Acceleration of this process may account for the rapid lethality seen with Ft SchuS4. In contrast, during sub-lethal infection with Ft LVS the pulmonary cellular response is characterized by a predominance of mature neutrophils and monocytes required for protection, suggesting a required threshold for lethal bacterial infection. Further, eliciting a mature phagocyte response provides transient, but dramatic, innate protection against Ft SchuS4. This study reveals that the nature of the myeloid cell response may be the primary determinant of host mortality versus survival following Francisella infection.

An Immature Myeloid/Myeloid-Suppressor Cell Response Associated with Necrotizing Inflammation Mediates Lethal Pulmonary Tularemia

Science.gov (United States)

Periasamy, Sivakumar; Avram, Dorina; McCabe, Amanda; MacNamara, Katherine C.; Sellati, Timothy J.; Harton, Jonathan A.

2016-01-01

Inhalation of Francisella tularensis (Ft) causes acute and fatal pneumonia. The lung cytokine milieu favors exponential Ft replication, but the mechanisms underlying acute pathogenesis and death remain unknown. Evaluation of the sequential and systemic host immune response in pulmonary tularemia reveals that in contrast to overwhelming bacterial burden or cytokine production, an overt innate cellular response to Ft drives tissue pathology and host mortality. Lethal infection with Ft elicits medullary and extra-medullary myelopoiesis supporting recruitment of large numbers of immature myeloid cells and MDSC to the lungs. These cells fail to mature and die, leading to subsequent necrotic lung damage, loss of pulmonary function, and host death that is partially dependent upon immature Ly6G+ cells. Acceleration of this process may account for the rapid lethality seen with Ft SchuS4. In contrast, during sub-lethal infection with Ft LVS the pulmonary cellular response is characterized by a predominance of mature neutrophils and monocytes required for protection, suggesting a required threshold for lethal bacterial infection. Further, eliciting a mature phagocyte response provides transient, but dramatic, innate protection against Ft SchuS4. This study reveals that the nature of the myeloid cell response may be the primary determinant of host mortality versus survival following Francisella infection. PMID:27015566

A screen for F1 hybrid male rescue reveals no major-effect hybrid lethality loci in the Drosophila melanogaster autosomal genome.

Science.gov (United States)

Cuykendall, Tawny N; Satyaki, P; Ji, Shuqing; Clay, Derek M; Edelman, Nathaniel B; Kimchy, Alexandra; Li, Ling-Hei; Nuzzo, Erin A; Parekh, Neil; Park, Suna; Barbash, Daniel A

2014-10-27

Hybrid sons between Drosophila melanogaster females and D. simulans males die as 3rd instar larvae. Two genes, D. melanogaster Hybrid male rescue (Hmr) on the X chromosome, and D. simulans Lethal hybrid rescue (Lhr) on chromosome II, interact to cause this lethality. Loss-of-function mutations in either gene suppress lethality, but several pieces of evidence suggest that additional factors are required for hybrid lethality. Here we screen the D. melanogaster autosomal genome by using the Bloomington Stock Center Deficiency kit to search for additional regions that can rescue hybrid male lethality. Our screen is designed to identify putative hybrid incompatibility (HI) genes similar to Hmr and Lhr which, when removed, are dominant suppressors of lethality. After screening 89% of the autosomal genome, we found no regions that rescue males to the adult stage. We did, however, identify several regions that rescue up to 13% of males to the pharate adult stage. This weak rescue suggests the presence of multiple minor-effect HI loci, but we were unable to map these loci to high resolution, presumably because weak rescue can be masked by genetic background effects. We attempted to test one candidate, the dosage compensation gene male specific lethal-3 (msl-3), by using RNA interference with short hairpin microRNA constructs targeted specifically against D. simulans msl-3 but failed to achieve knockdown, in part due to off-target effects. We conclude that the D. melanogaster autosomal genome likely does not contain additional major-effect HI loci. We also show that Hmr is insufficient to fully account for the lethality associated with the D. melanogaster X chromosome, suggesting that additional X-linked genes contribute to hybrid lethality. Copyright © 2014 Cuykendall et al.

Aberrations of holokinetic chromosomes and associated lethality after X-irradiation of meiotic stages in Tetranychus urticae Koch (acari, tetranychidae)

International Nuclear Information System (INIS)

Tempelaar, M.J.

1979-01-01

Chromosomes of the holokinetic organization type were irradiated with X-rays in various stages of meiosis in unfertillized eggs of Tetranychus urticae Koch. Visible cytological aberrations, lethality and sterility were investigated in subsequent generations. Chromosome fragments are the most frequently occuring light-microscopically visible chromosome aberrations; bridges are not formed. Contrary to expectations, the presence of fragments appears to be positively correlated with the occurrence of lethality; loss of fragments, missegregation and the measure of damage of the broken chromosome parts are involved. In contrast with monokinetic chromosomes the earliest lethality occurs only after about 10 divisions. The ratios between different embryonic lethality types (early vs. late) differ depending on the stage irradiated: in more compact chromatin, more serious damage (i.e. more early lethality syndromes) is induced than in less compact chromatin. In the progeny of the surviving males, neither translocations nor independent fragments are found; indirect evidence indicated the occasional presence of inversions. The presumtive inversions are induced more frequently in a chromatin-compact stage (metaphase I) than in a less compact one (telophase I). (Auth.)

Non-Lethal Weapons: A Technology Gap or Lack or Available Systems, Training, and Proper Application

Science.gov (United States)

2016-06-10

102-104. 31 Ibid., 103-104. 32 Michael Wines , “The Aftermath in Moscow: Post-Mortem in Moscow; Russia Names Drug in Raid, Defending Use,” New York...during the past three decades have increased awareness of the benefit of non- lethal options, but increased advocacy within the services has not led to a...during the execution of suitable missions that could benefit from less than lethal technology. Research and Development Once the directorate

Toxicity studies of drugs and chemicals in animals: An overview

OpenAIRE

S. Saganuwan

2017-01-01

Toxicity study is the investigation of either short or long-term toxic effects of a drug or chemical on animals. The toxicity is dose-dependent as asserted by Paracelsus over 500 years ago. However, short-term toxic effect is determined using median lethal dose (LD50) first introduced by Trevan in 1927 and revised many times. Presently there is a growing preponderance of rejection of scientific papers on acute toxicity study, simply because of the belief that in the current hazard and safety ...

Dominant lethals following administration of tritium (THO) to rat males

International Nuclear Information System (INIS)

Yagova, A.; Baev, I.; Bajrakova, A.

1976-01-01

Adult rat males were given a single intraperitoneal tritium (THO) injection at 0,01 or 0,001 mCi/g body weight (1/100 or 1/1000 of LDsub(50/30), respectively). Twelve days after treatment each male was mated to 3-5 intact females, and the latter were replaced by fresh ones every 12 following days over a 120-day period. Mated females were killed to score conceptions, corpora lutea, and live and dead embryos. Estimations were made of F 1 prenatal death rate (according to Bateman, 1958) and the frequency of induction of dominant lethal mutations (according to Roehrborn, 1970). The results observed indicated paternal exposure to tritium (THO) to produce dominant lethals both in pre- and post-meiotic germ cells in the rat. The extent of the genetic damage studied was found to depend on the amount of activity administered as well as on the time interval between treatment and conception. (author)

ZOOPLANKTON DIVERSITY AND ITS RELATIONSHIP WITH PHYSICO-CHEMICAL PARAMETERS IN MANI RESERVOIR OF WESTERN GHATS, REGION, HOSANAGAR TALUK, SHIVAMOGA DISTRICT KARNATAKA, INDIA

Directory of Open Access Journals (Sweden)

D. N. Veerendra

2012-01-01

Full Text Available Studies on relationship between zooplankton abundance and water quality parameter in Mani reservoir were made between January 2008 and December 2008. In the current investigation, impact of different physico-chemical parameters on zooplankton population was found. Ten genera of zooplankton were identified. The relationship between zooplankton and water quality parameters was varied from place to place depending upon the condition of the reservoir water.

Lethal/sublethal responses of Daphnia magna to acute norfloxacin contamination and changes in phytoplankton-zooplankton interactions induced by this antibiotic

Science.gov (United States)

Pan, Ying; Yan, Shi-Wei; Li, Ruo-Zhu; Hu, Yi-Wen; Chang, Xue-Xiu

2017-01-01

Although the well-known antibiotic norfloxacin (NOR) is recognized as an important environmental pollutant, little is known about its impacts on ecological processes, particularly on species interactions. In this paper, we quantified Daphnia magna (Crustacea, Cladocera) responses in mortality rate at lethal NOR concentrations (0, 25, 50, 100, 200, 300 and 400 mg L-1), and in heartbeat rate, swimming behavior and feeding rate (on the green alga Chlorella pyrenoidosa) at sublethal NOR concentrations (0, 25, 50 and 100 mg L-1) to determine the effects of this antibiotic in plankton systems. In 96-h-long lethal experiment, mortality rates of D. magna increased significantly with increasing NOR concentration and exposure time. In sublethal experiments, heartbeat rate decreased, while time ratio of vertical to horizontal swimming (TVH) and the duration of quiescence increased in D. magna individuals exposed to increasing NOR concentrations after 4 and 12 h of exposure. These collectively led to decreases in both average swimming ability and feeding rate, consistent with the positive relationship between average swimming ability and feeding rate. Overall, results indicate that, by affecting zooplankton heartbeat rate and behavior, NOR decreased feeding efficiency of D. magna even at low doses, therefore, it might seriously compromise ecosystem health and function.

Lethal and mutagenic effects of ion beams and γ-rays in Aspergillus oryzae.

Science.gov (United States)

Toyoshima, Yoshiyuki; Takahashi, Akemi; Tanaka, Hisaki; Watanabe, Jun; Mogi, Yoshinobu; Yamazaki, Tatsuo; Hamada, Ryoko; Iwashita, Kazuhiro; Satoh, Katsuya; Narumi, Issay

2012-12-01

Aspergillus oryzae is a fungus that is used widely in traditional Japanese fermentation industries. In this study, the lethal and mutagenic effects of different linear energy transfer (LET) radiation in freeze-dried conidia of A. oryzae were investigated. The lethal effect, which was evaluated by a 90% lethal dose, was dependent on the LET value of the ionizing radiation. The most lethal ionizing radiation among that tested was (12)C(5+) ion beams with an LET of 121keV/μm. The (12)C(5+) ion beams had a 3.6-times higher lethal effect than low-LET (0.2keV/μm) γ-rays. The mutagenic effect was evaluated by the frequency of selenate resistant mutants. (12)C(6+) ion beams with an LET of 86keV/μm were the most effective in inducing selenate resistance. The mutant frequency following exposure to (12)C(6+) ion beams increased with an increase in dose and reached 3.47×10(-3) at 700Gy. In the dose range from 0 to 700Gy, (12)C(5+) ion beams were the second most effective in inducing selenate resistance, the mutant frequency of which reached a maximum peak (1.67×10(-3)) at 400Gy. To elucidate the characteristics of mutation induced by ionizing radiation, mutations in the sulphate permease gene (sB) and ATP sulfurylase gene (sC) loci, the loss of function of which results in a selenate resistant phenotype, were compared between (12)C(5+) ion beams and γ-rays. We detected all types of transversions and transitions. For frameshifts, the frequency of a +1 frameshift was the highest in all cases. Although the incidence of deletions >2bp was generally low, deletions >20bp were characteristic for (12)C(5+) ion beams. γ-rays had a tendency to generate mutants carrying a multitude of mutations in the same locus. Both forms of radiation also induced genome-wide large-scale mutations including chromosome rearrangements and large deletions. These results provide new basic insights into the mutation breeding of A. oryzae using ionizing radiation. Crown Copyright © 2012. Published

Deletion of Indian hedgehog gene causes dominant semi-lethal Creeper trait in chicken

Science.gov (United States)

Jin, Sihua; Zhu, Feng; Wang, Yanyun; Yi, Guoqiang; Li, Junying; Lian, Ling; Zheng, Jiangxia; Xu, Guiyun; Jiao, Rengang; Gong, Yu; Hou, Zhuocheng; Yang, Ning

2016-01-01

The Creeper trait, a classical monogenic phenotype of chicken, is controlled by a dominant semi-lethal gene. This trait has been widely cited in the genetics and molecular biology textbooks for illustrating autosomal dominant semi-lethal inheritance over decades. However, the genetic basis of the Creeper trait remains unknown. Here we have utilized ultra-deep sequencing and extensive analysis for targeting causative mutation controlling the Creeper trait. Our results indicated that the deletion of Indian hedgehog (IHH) gene was only found in the whole-genome sequencing data of lethal embryos and Creeper chickens. Large scale segregation analysis demonstrated that the deletion of IHH was fully linked with early embryonic death and the Creeper trait. Expression analysis showed a much lower expression of IHH in Creeper than wild-type chickens. We therefore suggest the deletion of IHH to be the causative mutation for the Creeper trait in chicken. Our findings unravel the genetic basis of the longstanding Creeper phenotype mystery in chicken as the same gene also underlies bone dysplasia in human and mouse, and thus highlight the significance of IHH in animal development and human haploinsufficiency disorders. PMID:27439785

Calculation of baryon chemical potential and strangeness chemical potential in resonance matter

International Nuclear Information System (INIS)

Fu Yuanyong; Hu Shouyang; Lu Zhongdao

2006-01-01

Based on the high energy heavy-ion collisions statistical model, the baryon chemical potential and strangeness chemical potential are calculated for resonance matter with net baryon density and net strangeness density under given temperature. Furthermore, the relationship between net baryon density, net strangeness density and baryon chemical potential, strangeness chemical potential are analyzed. The results show that baryon chemical potential and strangeness chemical potential increase with net baryon density and net strangeness density increasing, the change of net baryon density affects baryon chemical potential and strangeness chemical potential more strongly than the change of net strangeness density. (authors)

Predicting chemically-induced skin reactions. Part II: QSAR models of skin permeability and the relationships between skin permeability and skin sensitization

Science.gov (United States)

Alves, Vinicius M.; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

2015-01-01

Skin permeability is widely considered to be mechanistically implicated in chemically-induced skin sensitization. Although many chemicals have been identified as skin sensitizers, there have been very few reports analyzing the relationships between molecular structure and skin permeability of sensitizers and non-sensitizers. The goals of this study were to: (i) compile, curate, and integrate the largest publicly available dataset of chemicals studied for their skin permeability; (ii) develop and rigorously validate QSAR models to predict skin permeability; and (iii) explore the complex relationships between skin sensitization and skin permeability. Based on the largest publicly available dataset compiled in this study, we found no overall correlation between skin permeability and skin sensitization. In addition, cross-species correlation coefficient between human and rodent permeability data was found to be as low as R2=0.44. Human skin permeability models based on the random forest method have been developed and validated using OECD-compliant QSAR modeling workflow. Their external accuracy was high (Q2ext = 0.73 for 63% of external compounds inside the applicability domain). The extended analysis using both experimentally-measured and QSAR-imputed data still confirmed the absence of any overall concordance between skin permeability and skin sensitization. This observation suggests that chemical modifications that affect skin permeability should not be presumed a priori to modulate the sensitization potential of chemicals. The models reported herein as well as those developed in the companion paper on skin sensitization suggest that it may be possible to rationally design compounds with the desired high skin permeability but low sensitization potential. PMID:25560673

The Effects of Posture, Body Armor and Other Equipment on Rifleman Lethality

National Research Council Canada - National Science Library

Kramlich, Gary R., II

2005-01-01

...? This study quantifies the effects of Soldier equipment on lethality through multi-factor logistic regression using data from range experiments with the 1st Brigade, 1st Infantry Division (Mechanized...

A phenomenological model for the structure-composition relationship of the high Tc cuprates based on simple chemical principles

International Nuclear Information System (INIS)

Alarco, J.A.; Talbot, P.C.

2012-01-01

A simple phenomenological model for the relationship between structure and composition of the high Tc cuprates is presented. The model is based on two simple crystal chemistry principles: unit cell doping and charge balance within unit cells. These principles are inspired by key experimental observations of how the materials accommodate large deviations from stoichiometry. Consistent explanations for significant HTSC properties can be explained without any additional assumptions while retaining valuable insight for geometric interpretation. Combining these two chemical principles with a review of Crystal Field Theory (CFT) or Ligand Field Theory (LFT), it becomes clear that the two oxidation states in the conduction planes (typically d 8 and d 9 ) belong to the most strongly divergent d-levels as a function of deformation from regular octahedral coordination. This observation offers a link to a range of coupling effects relating vibrations and spin waves through application of Hund’s rules. An indication of this model’s capacity to predict physical properties for HTSC is provided and will be elaborated in subsequent publications. Simple criteria for the relationship between structure and composition in HTSC systems may guide chemical syntheses within new material systems.

Estimation of the acute inhalation hazards of chemicals based on route-to-route and local endpoint extrapolation: Experience from Bulk Maritime Transport

NARCIS (Netherlands)

Höfer, T.; James, D.; Syversen, T.; Bowmer, T.

2011-01-01

Data on acute lethal inhalation toxicity from animal studies are commonly required for assessing the hazards to human health of volatile, gaseous and dusty chemicals or their mixtures. The International Maritime Organisation (IMO) made the provision of acute inhalation toxicity data a mandatory

Prymnesium parvum revisited: Relationship between allelopathy, ichthyotoxicity, and chemical profiles in 5 strains

Energy Technology Data Exchange (ETDEWEB)

Blossom, Hannah E., E-mail: hblossom@bio.ku.dk [Marine Biological Section, University of Copenhagen, Strandpromenaden 5, 3000 Helsingør (Denmark); Rasmussen, Silas A. [Department of Systems Biology, Technical University of Denmark, Søltofts Plads, Building 221, 2800 Kgs Lyngby (Denmark); Andersen, Nikolaj G. [Marine Biological Section, University of Copenhagen, Strandpromenaden 5, 3000 Helsingør (Denmark); Larsen, Thomas O.; Nielsen, Kristian F. [Department of Systems Biology, Technical University of Denmark, Søltofts Plads, Building 221, 2800 Kgs Lyngby (Denmark); Hansen, Per J. [Marine Biological Section, University of Copenhagen, Strandpromenaden 5, 3000 Helsingør (Denmark)

2014-12-15

Highlights: • Five strains of P. parvum were tested for toxicity towards rainbow trout and microalgae. • Toxicity towards microalgae was not correlated to toxicity towards fish. • A microalgal bioassay cannot be used as a reliable proxy for ichthyotoxicity. • Concentrations of GATs were low and not correlated to effects on fish or on algae. • P. parvum does not produce oleamide based on {sup 13}C labeling and extraction in glass. - Abstract: Bioassay-guided discovery of ichthyotoxic algal compounds using in vivo fish assays is labor intensive, costly, and highly regulated. Since the mode of action of most known algal-mediated fish-killing toxins is damage to the cell membranes in the gills, various types of cell-based bioassays are often used for bioassay guided purification of new ichthyotoxins. Here we tested the hypothesis that allelopathy is related to ichthyotoxicity and thus that a microalgal bioassay can be used as a proxy for ichthyotoxicity by comparing the toxicity of five strains of Prymnesium parvum toward rainbow trout (Oncorhynchus mykiss, 10 g) and the microalga Teleaulax acuta. No relationship between median effective concentrations (EC{sub 50}s) on fish and median lethal concentrations (LC{sub 50}s) on algae was observed in the 5 strains showing that a microalgal bioassay cannot be used as a proxy for ichthyotoxicity. Fish were more sensitive to P. parvum with EC{sub 50}s ranging from 6 × 10{sup 3} to 40 × 10{sup 3} cells ml{sup −1}, compared to the test alga where LC{sub 50}s ranged from 30 × 10{sup 3} to nearly non-toxic at 500 × 10{sup 3} cells ml{sup −1}. In addition, the cellular concentrations of two recently suggested ichthyotoxins produced by P. parvum, the “golden algae toxins”, GAT 512 and a novel GAT 510, did not show any relationship to either ichthyotoxicity or allelopathy, and are not the biologically relevant toxins, but are simply lipids found in algal chloroplasts. Finally, we demonstrate that the recently

Quantitative structure-activation barrier relationship modeling for Diels-Alder ligations utilizing quantum chemical structural descriptors.

Science.gov (United States)

Nandi, Sisir; Monesi, Alessandro; Drgan, Viktor; Merzel, Franci; Novič, Marjana

2013-10-30

In the present study, we show the correlation of quantum chemical structural descriptors with the activation barriers of the Diels-Alder ligations. A set of 72 non-catalysed Diels-Alder reactions were subjected to quantitative structure-activation barrier relationship (QSABR) under the framework of theoretical quantum chemical descriptors calculated solely from the structures of diene and dienophile reactants. Experimental activation barrier data were obtained from literature. Descriptors were computed using Hartree-Fock theory using 6-31G(d) basis set as implemented in Gaussian 09 software. Variable selection and model development were carried out by stepwise multiple linear regression methodology. Predictive performance of the quantitative structure-activation barrier relationship (QSABR) model was assessed by training and test set concept and by calculating leave-one-out cross-validated Q2 and predictive R2 values. The QSABR model can explain and predict 86.5% and 80% of the variances, respectively, in the activation energy barrier training data. Alternatively, a neural network model based on back propagation of errors was developed to assess the nonlinearity of the sought correlations between theoretical descriptors and experimental reaction barriers. A reasonable predictability for the activation barrier of the test set reactions was obtained, which enabled an exploration and interpretation of the significant variables responsible for Diels-Alder interaction between dienes and dienophiles. Thus, studies in the direction of QSABR modelling that provide efficient and fast prediction of activation barriers of the Diels-Alder reactions turn out to be a meaningful alternative to transition state theory based computation.

Thermodynamic chemical energy transfer mechanisms of non-equilibrium, quasi-equilibrium, and equilibrium chemical reactions

International Nuclear Information System (INIS)

Roh, Heui-Seol

2015-01-01

Chemical energy transfer mechanisms at finite temperature are explored by a chemical energy transfer theory which is capable of investigating various chemical mechanisms of non-equilibrium, quasi-equilibrium, and equilibrium. Gibbs energy fluxes are obtained as a function of chemical potential, time, and displacement. Diffusion, convection, internal convection, and internal equilibrium chemical energy fluxes are demonstrated. The theory reveals that there are chemical energy flux gaps and broken discrete symmetries at the activation chemical potential, time, and displacement. The statistical, thermodynamic theory is the unification of diffusion and internal convection chemical reactions which reduces to the non-equilibrium generalization beyond the quasi-equilibrium theories of migration and diffusion processes. The relationship between kinetic theories of chemical and electrochemical reactions is also explored. The theory is applied to explore non-equilibrium chemical reactions as an illustration. Three variable separation constants indicate particle number constants and play key roles in describing the distinct chemical reaction mechanisms. The kinetics of chemical energy transfer accounts for the four control mechanisms of chemical reactions such as activation, concentration, transition, and film chemical reactions. - Highlights: • Chemical energy transfer theory is proposed for non-, quasi-, and equilibrium. • Gibbs energy fluxes are expressed by chemical potential, time, and displacement. • Relationship between chemical and electrochemical reactions is discussed. • Theory is applied to explore nonequilibrium energy transfer in chemical reactions. • Kinetics of non-equilibrium chemical reactions shows the four control mechanisms

Lethal modifications of DNA via the transmutation of 32P and 33P incorporated in the genome of the S13 bacteriophage

International Nuclear Information System (INIS)

Cols, P.; Apelgot, S.; Guille, E.

1988-01-01

When circular single-standard DNA of phage S13 is labelled with 32 P or 33 P, the transmutations very efficiently bring about a loss of phage infectiousness (efficiency = 1 for 32 P and 0.73 for 33 P). For both radionuclides, the lethal efficiencies as well as the lethal events are different. In the case of 32 P, the lethal event is the loss of the circular integrity of the DNA molecule, occurring as a consequence of a systematic single strand-break caused by each 32 P decay (100%). Conversely, in the case of 33 P, the lethal events are either a single strand-break (40%) or a local stereochemical modification (33%). The same primary event, the substitution at each 33 P decay of a phosphate by a sulfate molecule, leads to one of these lethal events in relation to the decay site. Moreover, neither the phage adsorption nor its genome injection into bacteria depends on the physical state of the genome, and thus lethality is revealed at only the genetic level. (orig.)

Lethal and nonlethal violence against an intimate female partner: comparing male murderers to nonlethal abusers.

Science.gov (United States)

Dobash, R Emerson; Dobash, Russell P; Cavanagh, Kate; Medina-Ariza, Juanjo

2007-04-01

Men's lethal and nonlethal violence against an intimate female partner are compared. Various risk factors are examined to compare men's lethal and nonlethal violence against an intimate woman partner. Relative to abusers, men who kill are generally more conventional with respect to childhood backgrounds, education, employment, and criminal careers, are more likely to be possessive and jealous, and are more likely to be separated from their partner at the time of the event. Men who kill are more likely to have used violence against a previous partner, to have sexually assaulted and strangled the victim, and to have used a weapon or instrument. However, they were less likely to have been drunk at the time of the event and/or to have previously used violence against the woman they killed. Overall, the findings do not support the notion of a simple progression from nonlethal to lethal violence and raise some dilemmas for the growing area of risk assessment.

Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish

Directory of Open Access Journals (Sweden)

Liling Yang

2017-10-01

Full Text Available Background/Aims: Forsythia suspensa Vahl. (Oleaceae fruits are widely used in traditional Chinese medicine to treat pneumonia, typhoid, dysentery, ulcers and oedema. Antibacterial and anti-inflammatory activities have been reported for phillyrin (PHN, the main ingredient in Forsythia suspensa Vahl fruits, in vitro. However, the underlying mechanisms in vivo remain poorly defined. In this study, we discovered that PHN exerted potent anti-inflammatory effects in lethal LPS-induced neutrophil inflammation by suppressing the MyD88-dependent signalling pathway in zebrafish. Methods: LPS-yolk microinjection was used to induce a lethal LPS-infected zebrafish model. The effect of PHN on the survival of zebrafish challenged with lethal LPS was evaluated using survival analysis. The effect of PHN on neutrophil inflammation grading in vivo was assessed by tracking neutrophils with a transgenic line. The effects of PHN on neutrophil production and migration were analysed by SB+ cell counts during consecutive hours after modelling. Additionally, key cytokines and members of the MyD88 signalling pathway that are involved in inflammatory response were detected using quantitative RT-PCR. To assess gene expression changes during consecutive hours after modelling, the IL-1β, IL-6, TNF-α, MyD88, TRIF, ERK1/2, JNK, IκBa and NF-κB expression levels were measured. Results: PHN could protect zebrafish against a lethal LPS challenge in a dose-dependent manner, as indicated by decreased neutrophil infltration, reduced tissue necrosis and increased survival rates. Up-regulated IL-1β, IL-6 and TNF-α expression also showed the same tendencies of depression by PHN. Critically, PHN significantly inhibited the LPS-induced activation of MyD88, IκBa, and NF-κB but did not affect the expression of ERK1/2 MAPKs or JNK MAPKs in LPS-stimulated zebrafish. Additionally, PHN regulated the MyD88/IκBα/NF-κB signalling pathway by controlling IκBα, IL-1β, IL-6, and TNF

Ultraviolet-B lethal damage on Pseudomonas aeruginosa

International Nuclear Information System (INIS)

Degiorgi, C.F.; Fernandez, R.O.; Pizarro, R.A.

1996-01-01

Pseudomonas aeruginosa has shown an increased sensitivity compared with that of Escherichia coli and Enterobacter cloacae, when they were exposed to 0.4 kJ/m2 of ultraviolet-B radiation. The rapid decay in cell viability observed in Pseudomonas aeruginosa after the irradiation was influenced by factors such as culture media and the presence of pyocyanine during the irradiation. The radioinduced lethal damage could be prevented by photoreactivating treatment, indicating that pyrimidine dimer formation was the mechanism causing bacterial death. The results indicate that several environmental conditions may act as protective agents against ultraviolet-B-induced damage

Why the United States Must Adopt Lethal Autonomous Weapon Systems

Science.gov (United States)

2017-05-25

intelligence , Lethal Autonomous Weapon Systems, energy production, energy storage, three-dimensional printing , bandwidth improvements, computer...views on the morality of artificial intelligence (AI) and robotics technology. Eastern culture sees artificial intelligence as an economic savior...capable of improving their society. In contrast, Western culture regards artificial intelligence with paranoia, anxiety, and skepticism. As Eastern

Lethal and sublethal effects of selected insecticides and an insect growth regulator on the boll weevil (Coleoptera: Curculionidae) ectoparasitoid Catolaccus grandis (Hymenoptera: Pteromalidae).

Science.gov (United States)

Elzen, G W; Maldonado, S N; Rojas, M G

2000-04-01

A laboratory culture of Catolaccus grandis (Burks), an ectoparasitoid of the boll weevil, Anthonomus grandis grandis Boheman, was exposed to lethal and sublethal doses of insecticides and an insect growth regulator using a spray chamber bioassay. Materials tested were azinphos-methyl, endosulfan, fipronil, malathion, cyfluthrin, dimethoate, spinosad, methyl parathion, acephate, oxamyl, and tebufenozide. At full rates, spinosad was significantly less toxic to female C. grandis than other treatments except endosulfan. Fipronil and malathion were significantly more toxic to females than other treatments. Most of the chemicals tested were highly toxic to male C. grandis; spinosad was least toxic. At reduced rates, most of 4 selected chemicals tested were low in toxicity to C. grandis; however, a reduced rate of malathion was significantly more toxic to females than other treatments. No C. grandis pupae developed from parasitism during a 24-h treatment period with malathion or spinosad. The sex ratio of progeny from sprayed adults appeared to be unaffected by the treatments.

Antagonism at combined effects of chemical fertilizers and carbamate insecticides on the rice-field N2-fixing cyanobacterium Cylindrospermum sp. in vitro

OpenAIRE

Padhy Rabindra N.; Nayak Nabakishore; Rath Shakti

2014-01-01

Effects of chemical fertilizers (urea, super phosphate and potash) on toxicities of two carbamate insecticides, carbaryl and carbofuran, individually to the N2-fixing cyanobacterium, Cylindrospermum sp. were studied in vitro at partially lethal levels (below highest permissive concentrations) of each insecticide. The average number of vegetative cells between two polar heterocysts was 16.3 in control cultures, while the mean value of filament length increased in the presence of chemical ferti...

Combining chemical genomics screens in yeast to reveal spectrum of effects of chemical inhibition of sphingolipid biosynthesis

Directory of Open Access Journals (Sweden)

Giaever Guri

2009-01-01

Full Text Available Abstract Background Single genome-wide screens for the effect of altered gene dosage on drug sensitivity in the model organism Saccharomyces cerevisiae provide only a partial picture of the mechanism of action of a drug. Results Using the example of the tumor cell invasion inhibitor dihydromotuporamine C, we show that a more complete picture of drug action can be obtained by combining different chemical genomics approaches – analysis of the sensitivity of ρ0 cells lacking mitochondrial DNA, drug-induced haploinsufficiency, suppression of drug sensitivity by gene overexpression and chemical-genetic synthetic lethality screening using strains deleted of nonessential genes. Killing of yeast by this chemical requires a functional mitochondrial electron-transport chain and cytochrome c heme lyase function. However, we find that it does not require genes associated with programmed cell death in yeast. The chemical also inhibits endocytosis and intracellular vesicle trafficking and interferes with vacuolar acidification in yeast and in human cancer cells. These effects can all be ascribed to inhibition of sphingolipid biosynthesis by dihydromotuporamine C. Conclusion Despite their similar conceptual basis, namely altering drug sensitivity by modifying gene dosage, each of the screening approaches provided a distinct set of information that, when integrated, revealed a more complete picture of the mechanism of action of a drug on cells.

Sub-lethal effects of Vip3A toxin on survival, development and fecundity of Heliothis virescens and Plutella xylostella.

Science.gov (United States)

Gulzar, Asim; Wright, Denis J

2015-11-01

The assessment of sub-lethal effects is important to interpret the overall insecticide efficacy in controlling insect pest populations. In addition to the lethal effect, sub-lethal effects may also occur in exposed insects. Vegetative insecticidal proteins (Vips) have shown a broad spectrum of insecticidal activity against many insect pest species. In this study the sub-lethal effects of the Bacillus thuringiensis vegetative insecticidal toxin Vip3A on the development and reproduction of Heliothis virescens F. and Plutella xylostella L. were evaluated in the laboratory. The results indicated that the sub-lethal concentration of Vip3A increased the duration of the larval and pupal stages as compared with the control treatment for both species. The percent pupation and percent adult emergence were significantly lower for Vip3A-treated insects. The proportion of pairs that produced eggs and the longevity of adults were not significantly different between treatments. H. virescens and P. xylostella treated with Vip3A showed an 11 and 17 % decrease in their intrinsic rate of increase (rm) respectively compared with untreated insects. The results from this study will be helpful to develop the strategy to incorporate Vip 3A containing crops in an integrated pest management programme.

Transplantation of bone marrow cells into lethally irradiated mice

International Nuclear Information System (INIS)

Viktora, L.; Hermanova, E.

1978-01-01

Morphological changes were studied of megakaryocytes in the bone marrow and spleen of lethally irradiated mice (0.2 C/kg) after transplantation of living bone marrow cells. It was observed that functional trombopoietic megakaryocytes occur from day 15 after transplantation and that functional active megakaryocytes predominate in bone marrow and spleen from day 20. In addition, other types of cells, primarily granulocytes, were detected in some megakaryocytes. (author)

Dose-response tests and semi-field evaluation of lethal and sub-lethal effects of slow release pyriproxyfen granules (Sumilarv®0.5G) for the control of the malaria vectors Anopheles gambiae sensu lato.

Science.gov (United States)

Mbare, Oscar; Lindsay, Steven W; Fillinger, Ulrike

2013-03-14

Recently research has shown that larviciding can be an effective tool for integrated malaria vector control. Nevertheless, the uptake of this intervention has been hampered by the need to re-apply larvicides frequently. There is a need to explore persistent, environmentally friendly larvicides for malaria vector control to reduce intervention efforts and costs by reducing the frequency of application. In this study, the efficacy of a 0.5% pyriproxyfen granule (Surmilarv®0.5G, Sumitomo Chemicals) was assessed for the control of Anopheles gambiae sensu stricto and Anopheles arabiensis, the major malaria vectors in sub-Saharan Africa. Dose-response and standardized field tests were implemented following standard procedures of the World Health Organization's Pesticide Evaluation Scheme to determine: (i) the susceptibility of vectors to this formulation; (ii) the residual activity and appropriate retreatment schedule for field application; and, (iii) sub-lethal impacts on the number and viability of eggs laid by adults after exposure to Sumilarv®0.5G during larval development. Anopheles gambiae s.s. and An. arabiensis were highly susceptible to Sumilarv®0.5G. Estimated emergence inhibition (EI) values were very low and similar for both species. The minimum dosage that completely inhibited adult emergence was between 0.01-0.03 parts per million (ppm) active ingredient (ai). Compared to the untreated control, an application of 0.018 ppm ai prevented 85% (95% confidence interval (CI) 82%-88%) of adult emergence over six weeks under standardized field conditions. A fivefold increase in dosage of 0.09 ppm ai prevented 97% (95% CI 94%-98%) emergence. Significant sub-lethal effects were observed in the standardized field tests. Female An. gambiae s.s. that were exposed to 0.018 ppm ai as larvae laid 47% less eggs, and females exposed to 0.09 ppm ai laid 74% less eggs than females that were unexposed to the treatment. Furthermore, 77% of eggs laid by females exposed to 0

Dose–response tests and semi-field evaluation of lethal and sub-lethal effects of slow release pyriproxyfen granules (Sumilarv®0.5G) for the control of the malaria vectors Anopheles gambiae sensu lato

Science.gov (United States)

2013-01-01

Background Recently research has shown that larviciding can be an effective tool for integrated malaria vector control. Nevertheless, the uptake of this intervention has been hampered by the need to re-apply larvicides frequently. There is a need to explore persistent, environmentally friendly larvicides for malaria vector control to reduce intervention efforts and costs by reducing the frequency of application. In this study, the efficacy of a 0.5% pyriproxyfen granule (Surmilarv®0.5G, Sumitomo Chemicals) was assessed for the control of Anopheles gambiae sensu stricto and Anopheles arabiensis, the major malaria vectors in sub-Saharan Africa. Methods Dose–response and standardized field tests were implemented following standard procedures of the World Health Organization’s Pesticide Evaluation Scheme to determine: (i) the susceptibility of vectors to this formulation; (ii) the residual activity and appropriate retreatment schedule for field application; and, (iii) sub-lethal impacts on the number and viability of eggs laid by adults after exposure to Sumilarv®0.5G during larval development. Results Anopheles gambiae s.s. and An. arabiensis were highly susceptible to Sumilarv®0.5G. Estimated emergence inhibition (EI) values were very low and similar for both species. The minimum dosage that completely inhibited adult emergence was between 0.01-0.03 parts per million (ppm) active ingredient (ai). Compared to the untreated control, an application of 0.018 ppm ai prevented 85% (95% confidence interval (CI) 82%-88%) of adult emergence over six weeks under standardized field conditions. A fivefold increase in dosage of 0.09 ppm ai prevented 97% (95% CI 94%-98%) emergence. Significant sub-lethal effects were observed in the standardized field tests. Female An. gambiae s.s. that were exposed to 0.018 ppm ai as larvae laid 47% less eggs, and females exposed to 0.09 ppm ai laid 74% less eggs than females that were unexposed to the treatment. Furthermore, 77

Computed tomography of lethal medline granuloma

International Nuclear Information System (INIS)

Lee, Ho Suk; Kim, Tae Ho; Suh, Kyung Jin; Kim, Tae Hun; Kim, Yong Joo; Kang, Duk Sik

1991-01-01

In order to clarify the CT findings of lethal midline granuloma (LMG) diagnosed clinically or histopathologically, the authors retrospectively analyzed 12 patients who were seen at Kyungpook National University Hospital from February 1985 to August 1989. CT showed nasal mucosal thickening and / or soft tissue mass (9 case), spreading of the lesions along the facial subcutaneous fat plane (8 cases), invasion into the paranasal sinuses (5 cases), bone destruction (5 cases), nasopharyngeal mass lesion (2 cases), and extension of the lesion into the infratemporal fossa (1 case). In spite of the fact that CT does not make definitive diagnosis of LMG, it permits evaluation of the extent of the lesion, detection of the combined lesion, differential diagnosis, and close monitoring of its evolution under treatment

[Lethal effect after transmutation of 33P incorporated into bacteriophage S 13 and mechanisms of DNA double helix rupture].

Science.gov (United States)

Apelgot, S

1980-04-01

The experiments show the lethal effect of the beta decay of 33P incorporated in DNA of bacteriophage S 13. The lethal efficiency is high, 0.72 at 0 degrees C and 0.55 at--197 degrees C. The presence of a radical scavenger like AET has no influence. It was found previously that for such phages with single-stranded DNA, the lethal efficiency of 32P decay is unity, and that the lethal event is a DNA single-strand break, owing to the high energy of the nucleogenic 32S atom. As the recoil energy of the 33S atom is too low to account for such a break, it is suggested that the reorganization of the phosphate molecule into sulphate is able to bring about a DNA single-strand break with an efficiency as high as 0.7, at 0 degrees C. A model for the DNA double-strand-break produced by a transmutation processes is suggested.

[Study on the chemical components of edible oil fume in kitchen and its genotoxity on Drosophila].

Science.gov (United States)

Li, S; Wang, Y; Zhang, J; Zhao, X

1999-01-30

To study the chemical components of the condensate of edible oil fume in kitchen and its genotoxicity on Drosophila. Analysis for the chemical components was carried out by gas chromatography and mass spectra (GC/MS) and its genotoxicity was studied by sex linked recessive lethal (SLRL) test in Drosophila. A total of 74 organic compounds were found in samples of condensed oil from the fume in kitchen. It included hydroxylic acids, hydrocarbons, alcohols, esters, aldehydes, ketones, aromatic compounds, and steroids, etc. The total mutagenicity rates in SLRL test induced by the samples at concentrations of 110,320 and 960 mg/L were 0.1732%, 0.4306% and 0.1707% respectively. The sterility rates of the first broods were 2.564%, 2.056% and 2.845% at above 3 concentrations respectively(P < 0.05, as compared with the control). The mutagenicity rate of the second brood at 320 mg/L was 0.530% and that of the third brood at 110 mg/L 0.540%(P < 0.001). Some of the compounds in the condensate of edible oil fume were proved to have high recessive lethal effect and genotoxic effect on the reproductive system of Drosophila.

Toxicology Studies on Lewisite and Sulfur Mustard Agents: Modified Dominant Lethal Study of Sulfur Mustard in Rats Final Report

Energy Technology Data Exchange (ETDEWEB)

Sasser, L. B.; Cushing, J. A.; Kalkwarf, D. R.; Buschbom, R. L.

1989-05-01

Occupational health standards have not been established for sulfur mustard (HD) [bis{2-chloroethyl)-sulfide) ' a strong alkylating agent with known mutagenic properties. Little, however, is known about the mutagenic activity of HD in mammalian species and data regarding the dominant lethal effects of HD are ambiguous. The purpose of this study was to determine the dominant lethal effect in male and female rats orally exposed to HD. The study was conducted in two phases; a female dominant lethal phase and a male dominant lethal phase. Sprague-Dawley rats of each sex were administered 0.08, 0.20, or 0.50 mg/kg HD in sesame oil 5 days/week for 10 weeks. For the female phase, treated or untreated males were mated with treated females and their fetuses were evaluated at approximately 14 days after copulation. For the male dominant lethal phase, treated males cohabited with untreated femal (during 5 days of each week for 10 weeks) and females were sacrificed for fetal evaluation 14 days after the midweek of cohabitation during each of the 10 weeks. The appearance and behavior of the rats were unremarkable throughout the experiment and there were no treatment-related deaths. Growth rates were reduced in both female and male rats treated with 0.50 mg/kg HD. Indicators of reproductive performance did not demonstrate significant female dominant lethal effects, although significant male dominant lethal effects were observed at 2 and 3 week post-exposure. These effects included increases of early fetal resorptions and preimplantation losses and decreases of total live embryo implants. These effects were most consistently observed at a dose of 0.50 mg/kg, but frequently occurred at the lower doses. Although no treatment-related effects on male reproductive organ weights or sperm motility were found, a significant increase in the percentage of abnormal sperm was detected in males exposed to 0. 50 mg/kg HD. The timing of these effects is consistent with an effect during the

Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities.

Science.gov (United States)

Peters, Diane E; Hoover, Benjamin; Cloud, Loretta Grey; Liu, Shihui; Molinolo, Alfredo A; Leppla, Stephen H; Bugge, Thomas H

2014-09-01

We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5-3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. Published by Elsevier Inc.

PENGARUH PENGGUNAAN LETHAL OVITRAP TERHADAP POPULASI NYAMUK AEDES SP SEBAGAI VEKTOR DEMAM BERDARAH DENGUE

Directory of Open Access Journals (Sweden)

Tri Ramadhani

2013-09-01

Full Text Available ABSTRACT. Field evaluation against lethal ovitrap (LO to control dengue vector Aedes mosquitoes carried intwo endemic areas (Bojongsari and Ledug in Banyumas. Lethal ovitrap made ?with the intent to kill mosquito,because mosquitoes will lay eggs containing ovistrip contact with the insecticide and the relatively short time todie.The aim of research to assess the effect of LO applications with the Aedes of mosquito populations sp. Thisstudy includes a quasi experimental design with pretest-posttest control group without randomization. Researchsites in dengue endemic areas with a total sample of 100 houses in each treatment and control areas. Populationsof Aedes sp measured every week for three weeks prior to the intervention and twelve weeks during theintervention. The mean density of Aedes sp compared before and after intervention and between the treatment andcontrol. Results showed mean mosquito density before and after the intervention in the treatment group of 0.07(p-value 0.044, whereas in the control group by 0037 ( p-value 0341. Use LO made ?with the addition ofinsecticide active cypermetrin on ovistrip impact on the density of Aedes sp in the residential neighborhood.Keywords: lethal ovitrap, DHF, Aedes sp

Sterilization and lethal gamma radiation doses on adults and eggs of Sitotroga Cerealella (OLIVIER)

International Nuclear Information System (INIS)

Wiendl, F.M.; Bovi, O.A.; Arthur, V.

1975-04-01

The influence of lethal doses of radiation from a cobalt 60 gamma source on eggs, adults and fertitility of Sitotroga Cerealella (Olivier) is described. Eggs irradiated with a dose of 14 Krad still showed viability of 16.1%. On longevity doses up to 70 Krad were usually non lethal but some variation could be observed related to the larval diet. Females fertilized by males irradiated with a dose of 70 Krad produced 36% fertile eggs. When the females were irradiated with the same dose, their fertility dropped to 2.2% and when both sexes were irradiated with a 60 Krad dose, the fertility was 28.8%

A novel plant glutathione S-transferase/peroxidase suppresses Bax lethality in yeast

DEFF Research Database (Denmark)

Kampranis, S C; Damianova, R; Atallah, M

2000-01-01

The mammalian inducer of apoptosis Bax is lethal when expressed in yeast and plant cells. To identify potential inhibitors of Bax in plants we transformed yeast cells expressing Bax with a tomato cDNA library and we selected for cells surviving after the induction of Bax. This genetic screen allows...... for the identification of plant genes, which inhibit either directly or indirectly the lethal phenotype of Bax. Using this method a number of cDNA clones were isolated, the more potent of which encodes a protein homologous to the class theta glutathione S-transferases. This Bax-inhibiting (BI) protein was expressed...... in Escherichia coli and found to possess glutathione S-transferase (GST) and weak glutathione peroxidase (GPX) activity. Expression of Bax in yeast decreases the intracellular levels of total glutathione, causes a substantial reduction of total cellular phospholipids, diminishes the mitochondrial membrane...

Lethal Encephalitozoon cuniculi genotype III infection in Steppe lemmings (Lagurus lagurus)

Czech Academy of Sciences Publication Activity Database

Hofmannová, L.; Sak, Bohumil; Jekl, V.; Mináriková, A.; Škorič, M.; Kváč, Martin

2014-01-01

Roč. 205, 1-2 (2014), s. 357-360 ISSN 0304-4017 R&D Projects: GA ČR(CZ) GAP505/11/1163 Institutional support: RVO:60077344 Keywords : Encephalitozoon cuniculi genotype III * Steppe lemmings * Lethal infection * PCR * Histology Subject RIV: EG - Zoology Impact factor: 2.460, year: 2014

Late radiation effects in animals surviving lethal irradiation

International Nuclear Information System (INIS)

Dimitrov, L.A.

1974-01-01

Animals (rats, mice, dogs) survived lethal irradiation by means of prophylactic-therapeutic treatments or previously irradiated, were studied for late radiation effects: life span, cachexia and fat growing of hypophysical type, tissue or organ hypoplasia manifested by disturbed hemopoiesis, suppressed function of adrenal gland, etc., suppressed immune reactivity of the irradiated organism, atypical biochemical changes in DNA and protein metabolism, epilation, chronic dermatitis, ulcerations, reduced reproductivity or full sterility, damage of kidneys leading to nephrosclerosis, dishormonal states, cataracts, diffuse sclerotic processes, various kinds of malignant and non-malignant tumors. In these cases hemopoiesis compensated for a definite time peripheral blood composition, but during the late period it showed features of incompleteness: shorter life survival of erythrocytes and thrombocytes manifested by a decreased binding of labelled methionine in these blood elements, anemia and relative thrombocytopenia sometimes with an increased number of polychromatic erythrocytes in peripheral blood and a decreased number of reticulocytes at the same time; lymphopenia and relative leucopenia with an increased number of hypersegmented neutrophils. Decreased reproductivity and atypical biochemical changes available in the first generation of the irradiated animals showed the probable role of mutagenic factors in the emergence of some late radiation effects. A significant part of late radiation sequences were due to neuro-endocrine desintegrations which lead to a disturbed supply of the vessels and afterwards to their sclerosis. Some of the described late radiation effects were also observed in biological controls as festures of ageing while in irradiated animals they were manifested in an earlier period. After application of optimal amounts radioprotectors (AET, cysteamine, serotonin) a more marked protective effect is demonstrated in the early reactions (time survival

Fluorescent-light-induced lethality and DNA repair in normal and xeroderma pigmentosum fibroblasts

International Nuclear Information System (INIS)

Ritter, M.A.; Williams, J.R.

1981-01-01

Cell survival and induction of endonuclease-sensitive sites in DNA were measured in human fibroblast cells exposed to fluorescent light or germicidal ultraviolet light. Cells from a xeroderma pigmentosum patient were hypersensitive to cell killing by fluorescent light, although less so than for germicidal ultraviolet light. Xeroderma pigmentosum cells were deficient in the removal of fluorescent light-induced endonuclease sites that are probably pyrimidine dimers, and both the xeroderma pigmentosum and normal cells removed these sites with kinetics indistinguishable from those for ultraviolet light-induced sites. A comparison of fluorescent with ultraviolet light data demonstrates that there are markedly fewer pyrimidine dimers per lethal event for fluorescent than for ultraviolet light, suggesting a major role for non-dimer damage in fluorescent lethality. (Auth.)

Dominant lethal mutations and histological changes produced in mouse oocytes by gamma irradiation

International Nuclear Information System (INIS)

Vyglenov, A.; Baev, I.; Rupova, I.; Kusheva, R.

1976-01-01

Mouse female were exposed to a total dose of 500 or 1000 rad 137 Cs gamma rays delivered at 0.01 rad/min. Effects were scored at 1, 5, 7, and 10 weeks after cessation of treatment. Histologically, ovaria in the 500 rad group showed a decrease up to 11% in follicle numbers as compared to controls; with the prolongation of the time after exposure, a further fall in follicle numbers is observed. In the 1000 rad group, depopulation of ovaria was complete. With the 500 rad dose, total dominant lethality was found to be increased for any of the time intervals between radiation exposure and conception; postimplantation dominant lethality was comparatively low, with similar scores between the weeks investigated. (author)

Galantamine is a novel post-exposure therapeutic against lethal VX challenge

International Nuclear Information System (INIS)

Hilmas, Corey J.; Poole, Melissa J.; Finneran, Kathryn; Clark, Matthew G.; Williams, Patrick T.

2009-01-01

The ability of galantamine hydrobromide (GAL HBr) treatment to antagonize O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothiolate (VX)-induced lethality, impairment of muscle tension, and electroencephalographic (EEG) changes was assessed in guinea pigs. Guinea pigs were challenged with 16.8 μg/kg VX (2LD50). One min after challenge, animals were administered 0.5 mg/kg atropine sulfate (ATR) and 25 mg/kg pyridine-2-aldoxime methochloride (2-PAM). In addition, guinea pigs were given 0, 1, 2, 4, 8 or 10 mg/kg GAL as a post-exposure treatment immediately prior to ATR and 2-PAM. Animals were either monitored for 24-h survival, scheduled for electroencephalography (EEG) recording, or euthanized 60 min later for measurement of indirectly-elicited muscle tension in the hemidiaphragm. Post-exposure GAL therapy produced a dose-dependent increase in survival from lethal VX challenge. Optimal clinical benefits were observed in the presence of 10 mg/kg GAL, which led to 100% survival of VX-challenged guinea pigs. Based on muscle physiology studies, GAL post-exposure treatment protected the guinea pig diaphragm, the major effector muscle of respiration, from fatigue, tetanic fade, and muscular paralysis. Protection against the paralyzing effects of VX was dose-dependent. In EEG studies, GAL did not alter seizure onset for all doses tested. At the highest dose tested (10 mg/kg), GAL decreased seizure duration when administered as a post-exposure treatment 1 min after VX. GAL also reduced the high correlation associated between seizure activity and lethality after 2LD50 VX challenge. GAL may have additional benefits both centrally and peripherally that are unrelated to its established mechanism as a reversible acetylcholinesterase inhibitor (AChEI).

Derangement of cellular plasma membranes due to non-lethal radiation doses

International Nuclear Information System (INIS)

Koeteles, G.J.; Kubasova, T.; Somosy, Z.; Horvath, L.

1983-01-01

Earlier observations in the laboratory on fibroblasts and various blood cells of animal and human origins pointed to alteration of concanavalin A binding sites of plasma membranes as well as to concomitant morphological changes and scanning electron microscopic appearance of cell surfaces following sub-lethal doses of X-, fission neutron and beta irradiations. The effects appeared early and existed temporarily; their intensities and the restitution of membrane function depended on radiation doses, types and conditions of cells. In the present paper further aspects of structural and functional derangements of plasma membranes are introduced which were provoked by X- and tritium beta irradiation in the dose range up to 2.5 Gy and in the concentration range from 3.7 kBq/mL, respectively. The state of membrane structure was followed by bindings of various ligands of different receptor requirements, concanavalin A, cationized ferritin and polio virus. In the case of X-irradiation the binding conditions suggest the shift of overall negative surface charges to less negative ones. It was also found that radiation-induced phenomena appear on the cell surface unevenly. Long- and short-term treatments of cells with 3 H-thymidine and 3 H-water also perturb the plasma membrane; beta irradiation affects it directly. Membrane structure and function are suggested to offer good biological models to study correlation of energy deposition and biological effects, both restricted to domains of nanometre range. The data give evidence for radiation-induced membrane alterations in the sub-lethal or non-lethal ranges which might have consequences in the development of stochastic and non-stochastic effects. (author)

Behavioral responses of the estuarine calanoid copepod Eurytemora affinis to sub-lethal concentrations of waterborne pollutants

International Nuclear Information System (INIS)

Michalec, François-Gaël; Holzner, Markus; Menu, Dominique; Hwang, Jiang-Shiou; Souissi, Sami

2013-01-01

Highlights: •We studied the effects of sub-lethal exposure to pollutants on Eurytemora affinis swimming behavior. •Nonylphenol, cadmium and polycyclic aromatic hydrocarbons caused hyperactivity. •Effects were observable within 30 min of exposure and persisted during a depuration period. •The response resembles an escape reaction allowing copepods to evade stressful conditions. -- Abstract: Estuarine waters contain a variety of chemicals which affect to various extents the behavior of aquatic organisms. Little is known, however, on the behavioral response of copepods. The present study shows the results of laboratory experiments investigating the immediate effects of sub-lethal concentrations of three commonly found contaminants on the three-dimensional swimming behavior of the estuarine calanoid copepod Eurytemora affinis. Nonylphenol at 2 μg L −1 , cadmium at 45 ng L −1 and a mixture of low to medium molecular weight polycyclic aromatic hydrocarbons at 40 ng L −1 all affected the swimming behavior of E. affinis adults, increasing both swimming speed and activity. In most cases, effects were observable within 30 min of exposure and persisted or faded during a period of depuration in uncontaminated water of similar duration. In ovigerous females exposed to Cd and PAHs, effects appeared to be more pronounced during the depuration period, suggesting that carrying ovisacs may impair recovery. We quantified differences in the distribution of swimming speed values by considering the relative frequencies of periods of break, slow and fast swimming and we observed a trend toward faster movements in the presence of pollutants. The degree of trajectory complexity, estimated through their fractal dimension, was unaffected by pollutants. Since both narcotic and non-narcotic pollutants induced hyperactivity, our results suggest that changes in behavior after a short-term exposure may be independent of the general mode of action of the chemicals. The increase in

Behavioral responses of the estuarine calanoid copepod Eurytemora affinis to sub-lethal concentrations of waterborne pollutants

Energy Technology Data Exchange (ETDEWEB)

Michalec, François-Gaël [Université Lille Nord de France, F-59000 Lille (France); USTL, LOG, Station Marine de Wimereux, F-62930 Wimereux (France); CNRS, UMR 8187, F-62930 Wimereux (France); National Taiwan Ocean University, Institute of Marine Biology, Keelung, Taiwan, ROC (China); Holzner, Markus [Institute of Environmental Engineering, ETH Zürich (Switzerland); Menu, Dominique [Université Lille Nord de France, F-59000 Lille (France); USTL, LOG, Station Marine de Wimereux, F-62930 Wimereux (France); CNRS, UMR 8187, F-62930 Wimereux (France); Hwang, Jiang-Shiou [National Taiwan Ocean University, Institute of Marine Biology, Keelung, Taiwan, ROC (China); Souissi, Sami, E-mail: sami.souissi@univ-lille1.fr [Université Lille Nord de France, F-59000 Lille (France); USTL, LOG, Station Marine de Wimereux, F-62930 Wimereux (France); CNRS, UMR 8187, F-62930 Wimereux (France)

2013-08-15

Highlights: •We studied the effects of sub-lethal exposure to pollutants on Eurytemora affinis swimming behavior. •Nonylphenol, cadmium and polycyclic aromatic hydrocarbons caused hyperactivity. •Effects were observable within 30 min of exposure and persisted during a depuration period. •The response resembles an escape reaction allowing copepods to evade stressful conditions. -- Abstract: Estuarine waters contain a variety of chemicals which affect to various extents the behavior of aquatic organisms. Little is known, however, on the behavioral response of copepods. The present study shows the results of laboratory experiments investigating the immediate effects of sub-lethal concentrations of three commonly found contaminants on the three-dimensional swimming behavior of the estuarine calanoid copepod Eurytemora affinis. Nonylphenol at 2 μg L{sup −1}, cadmium at 45 ng L{sup −1} and a mixture of low to medium molecular weight polycyclic aromatic hydrocarbons at 40 ng L{sup −1} all affected the swimming behavior of E. affinis adults, increasing both swimming speed and activity. In most cases, effects were observable within 30 min of exposure and persisted or faded during a period of depuration in uncontaminated water of similar duration. In ovigerous females exposed to Cd and PAHs, effects appeared to be more pronounced during the depuration period, suggesting that carrying ovisacs may impair recovery. We quantified differences in the distribution of swimming speed values by considering the relative frequencies of periods of break, slow and fast swimming and we observed a trend toward faster movements in the presence of pollutants. The degree of trajectory complexity, estimated through their fractal dimension, was unaffected by pollutants. Since both narcotic and non-narcotic pollutants induced hyperactivity, our results suggest that changes in behavior after a short-term exposure may be independent of the general mode of action of the chemicals. The

Spondyloepiphyseal dysplasia congenita. A cause of lethal neonatal dwarfism

Energy Technology Data Exchange (ETDEWEB)

Macpherson, R.I.; Wood, B.P.

1980-07-01

Spondyloepiphyseal dysplasia congenita is a form of primarily short trunk dwarfism, that is manifest at birth but generally has not been regarded as a cause of lethal neonatal dwarfism. Seven neonates with severe dwarfism are presented. The first survived the newborn period, but the other six were early neonatal deaths. All displayed the clinical and radiologic features of spondyloepiphyseal dysplasia congenita. The striking similarities between spondyloepiphyseal dysplasia congenita and achondrogenesis type 2 are discussed.

Torrance type of lethal neonatal short-limbed platyspondylic dwarfism

Energy Technology Data Exchange (ETDEWEB)

Kaibara, N.; Yokoyama, K.; Nakano, H.

1983-06-01

A rare case of lethal neonatal short-limbed platyspondylic dwarfism is described. Roentgenographic features of this case, distinctly different from those of the classical thanatophoric dysplasia, are indistinguishable from the other three types of short-limbed platyspondylic dwarfism. Histologic features of the cartilage in this case are not very different from those of the Torrance type, but the presence of focal disruption of column formation in this case suggests a wider spectrum for this entity.

Doctor of Philosophy Thesis in Military Informatics : Lethal Autonomy of Weapons is Designed and/or Recessive

OpenAIRE

Nyagudi, Nyagudi Musandu

2016-01-01

p { margin-bottom: 0.1in; line-height: 120%; } My original contribution to knowledge is : Any weapon that exhibits intended and/or untended lethal autonomy in targeting and interdiction – does so by way of design and/or recessive flaw(s) in its systems of control – any such weapon is capable of war-fighting and other battle-space interaction in a manner that its Human Commander does not anticipate. A lethal autonomous weapons is therefore independently capable of ex...

Relationships between botanical and chemical composition of forages: a multivariate approach to grasslands in the Western Italian Alps.

Science.gov (United States)

Ravetto Enri, Simone; Renna, Manuela; Probo, Massimiliano; Lussiana, Carola; Battaglini, Luca M; Lonati, Michele; Lombardi, Giampiero

2017-03-01

Plant composition of species-rich mountain grasslands can affect the sensorial and chemical attributes of dairy and meat products, with implications for human health. A multivariate approach was used to analyse the complex relationships between vegetation characteristics (botanical composition and plant community variables) and chemical composition (proximate constituents and fatty acid profile) in mesophilic and dry vegetation ecological groups, comprising six different semi-natural grassland types in the Western Italian Alps. Mesophilic and dry grasslands were comparable in terms of phenology, biodiversity indices and proportion of botanical families. The content of total fatty acids and that of the most abundant fatty acids (alpha-linolenic, linoleic and palmitic acids) were mainly associated to nutrient-rich plant species, belonging to the mesophilic grassland ecological group. Mesophilic grasslands showed also higher values of crude protein, lower values of fibre content and they were related to higher pastoral values of vegetation compared to dry grasslands. The proximate composition and fatty acid profile appeared mainly single species dependent rather than botanical family dependent. These findings highlight that forage from mesophilic grasslands can provide higher nutritive value for ruminants and may be associated to ruminant-derived food products with a healthier fatty acid profile. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Predicting chemically-induced skin reactions. Part II: QSAR models of skin permeability and the relationships between skin permeability and skin sensitization

Energy Technology Data Exchange (ETDEWEB)

Alves, Vinicius M. [Laboratory of Molecular Modeling and Design, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO 74605-220 (Brazil); Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Muratov, Eugene [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Laboratory of Theoretical Chemistry, A.V. Bogatsky Physical–Chemical Institute NAS of Ukraine, Odessa 65080 (Ukraine); Fourches, Denis [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Strickland, Judy; Kleinstreuer, Nicole [ILS/Contractor supporting the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), P.O. Box 13501, Research Triangle Park, NC 27709 (United States); Andrade, Carolina H. [Laboratory of Molecular Modeling and Design, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO 74605-220 (Brazil); Tropsha, Alexander, E-mail: alex_tropsha@unc.edu [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States)

2015-04-15

Skin permeability is widely considered to be mechanistically implicated in chemically-induced skin sensitization. Although many chemicals have been identified as skin sensitizers, there have been very few reports analyzing the relationships between molecular structure and skin permeability of sensitizers and non-sensitizers. The goals of this study were to: (i) compile, curate, and integrate the largest publicly available dataset of chemicals studied for their skin permeability; (ii) develop and rigorously validate QSAR models to predict skin permeability; and (iii) explore the complex relationships between skin sensitization and skin permeability. Based on the largest publicly available dataset compiled in this study, we found no overall correlation between skin permeability and skin sensitization. In addition, cross-species correlation coefficient between human and rodent permeability data was found to be as low as R{sup 2} = 0.44. Human skin permeability models based on the random forest method have been developed and validated using OECD-compliant QSAR modeling workflow. Their external accuracy was high (Q{sup 2}{sub ext} = 0.73 for 63% of external compounds inside the applicability domain). The extended analysis using both experimentally-measured and QSAR-imputed data still confirmed the absence of any overall concordance between skin permeability and skin sensitization. This observation suggests that chemical modifications that affect skin permeability should not be presumed a priori to modulate the sensitization potential of chemicals. The models reported herein as well as those developed in the companion paper on skin sensitization suggest that it may be possible to rationally design compounds with the desired high skin permeability but low sensitization potential. - Highlights: • It was compiled the largest publicly-available skin permeability dataset. • Predictive QSAR models were developed for skin permeability. • No concordance between skin

Predicting chemically-induced skin reactions. Part II: QSAR models of skin permeability and the relationships between skin permeability and skin sensitization

International Nuclear Information System (INIS)

Alves, Vinicius M.; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

2015-01-01

Skin permeability is widely considered to be mechanistically implicated in chemically-induced skin sensitization. Although many chemicals have been identified as skin sensitizers, there have been very few reports analyzing the relationships between molecular structure and skin permeability of sensitizers and non-sensitizers. The goals of this study were to: (i) compile, curate, and integrate the largest publicly available dataset of chemicals studied for their skin permeability; (ii) develop and rigorously validate QSAR models to predict skin permeability; and (iii) explore the complex relationships between skin sensitization and skin permeability. Based on the largest publicly available dataset compiled in this study, we found no overall correlation between skin permeability and skin sensitization. In addition, cross-species correlation coefficient between human and rodent permeability data was found to be as low as R 2 = 0.44. Human skin permeability models based on the random forest method have been developed and validated using OECD-compliant QSAR modeling workflow. Their external accuracy was high (Q 2 ext = 0.73 for 63% of external compounds inside the applicability domain). The extended analysis using both experimentally-measured and QSAR-imputed data still confirmed the absence of any overall concordance between skin permeability and skin sensitization. This observation suggests that chemical modifications that affect skin permeability should not be presumed a priori to modulate the sensitization potential of chemicals. The models reported herein as well as those developed in the companion paper on skin sensitization suggest that it may be possible to rationally design compounds with the desired high skin permeability but low sensitization potential. - Highlights: • It was compiled the largest publicly-available skin permeability dataset. • Predictive QSAR models were developed for skin permeability. • No concordance between skin sensitization and

Alpha-beta T cells provide protection against lethal encephalitis in the murine model of VEEV infection

International Nuclear Information System (INIS)

Paessler, Slobodan; Yun, Nadezhda E.; Judy, Barbara M.; Dziuba, Natallia; Zacks, Michele A.; Grund, Anna H.; Frolov, Ilya; Campbell, Gerald A.; Weaver, Scott C.; Estes, D. Mark

2007-01-01

We evaluated the safety and immunogenicity of a chimeric alphavirus vaccine candidate in mice with selective immunodeficiencies. This vaccine candidate was highly attenuated in mice with deficiencies in the B and T cell compartments, as well as in mice with deficient gamma-interferon responsiveness. However, the level of protection varied among the strains tested. Wild type mice were protected against lethal VEEV challenge. In contrast, alpha/beta (αβ) TCR-deficient mice developed lethal encephalitis following VEEV challenge, while mice deficient in gamma/delta (γδ) T cells were protected. Surprisingly, the vaccine potency was diminished by 50% in animals lacking interferon-gamma receptor alpha chain (R1)-chain and a minority of vaccinated immunoglobulin heavy chain-deficient (μMT) mice survived challenge, which suggests that neutralizing antibody may not be absolutely required for protection. Prolonged replication of encephalitic VEEV in the brain of pre-immunized mice is not lethal and adoptive transfer experiments indicate that CD3 + T cells are required for protection

Combination of opium smoking and hypercholesterolemia augments susceptibility for lethal cardiac arrhythmia and atherogenesis in rabbit.

Science.gov (United States)

Najafipour, Hamid; Joukar, Siyavash

2012-09-01

Opium consumption is increasing in some eastern societies, where it is grown. We investigated the effect of opium smoking on plasma atherogenic index and incidence of lethal cardiac arrhythmia, i.e. ventricular tachycardia (VT) and ventricular fibrillation (VF) in rabbits. Animals were divided into two-, normo- and hyper-cholesterolemic main groups fed with normal or high cholesterol diet prior and during short-term and long-term exposure to opium smoke. Then, isoproterenol (3mg/kg, i.p.) was injected to induce cardiac ischemia and animals were followed for 3h for counting of lethal arrhythmia incidence. Long-term opium smoking significantly increased the plasma atherogenic index. In ischemic hearts, opium smoking along with hypercholesterolemia significantly enhanced the incidence of fatal arrhythmia. This vulnerability was not mediated by changes in QT interval. These data suggest that opium smoking, especially in hypercholesterolemic conditions, can be a predisposing factor for atherogenesis and lethal arrhythmia. Copyright © 2012 Elsevier B.V. All rights reserved.

Thermodynamics of the living organisms. Allometric relationship between the total metabolic energy, chemical energy and body temperature in mammals

Science.gov (United States)

Atanasov, Atanas Todorov

2017-11-01

The study present relationship between the total metabolic energy (ETME(c), J) derived as a function of body chemical energy (Gchem, J) and absolute temperature (Tb, K) in mammals: ETME(c) =Gchem (Tb/Tn). In formula the temperature Tn =2.73K appears normalization temperature. The calculated total metabolic energy ETME(c) differs negligible from the total metabolic energy ETME(J), received as a product between the basal metabolic rate (Pm, J/s) and the lifespan (Tls, s) of mammals: ETME = Pm×Tls. The physical nature and biological mean of the normalization temperature (Tn, K) is unclear. It is made the hypothesis that the kTn energy (where k= 1.3806×10-23 J/K -Boltzmann constant) presents energy of excitation states (modes) in biomolecules and body structures that could be in equilibrium with chemical energy accumulated in body. This means that the accumulated chemical energy allows trough all body molecules and structures to propagate excitations states with kTn energy with wavelength in the rage of width of biological membranes. The accumulated in biomolecules chemical energy maintains spread of the excited states through biomolecules without loss of energy.

Arrest of irradiated G1, S, or G2 cells at mitosis using nocodazole promotes repair of potentially lethal damage

International Nuclear Information System (INIS)

Iliakis, G.; Nuesse, M.

1984-01-01

The ability of synchronized Ehrlich ascites tumor cells, irradiated in G1, S, and G2 phases, to repair potentially lethal damage when arrested at mitosis by using 0.4 μg/ml nocodazole, a specific inhibitor of microtubule polymerization, has been studied. Cells irradiated in these phases were found to repair potentially lethal damage at mitosis. The extent of this repair was similar to that observed for cells irradiated at the same stages in the cell cycle but allowed to repair potentially lethal damage by incubating in balanced salt solution for 6 hr after X irradiation

Lethal mutation of internal irradiation brown planthopper (Nilaparvita lugens Stal)

International Nuclear Information System (INIS)

Wahid, R.A.

1988-01-01

The moulting IVth of BPH nympha were irradiated internally with radiophosphorous 32-P 1 uCi/ml, 10 uCi/ml, 50 uCi/ml, 100 uCi/ml, and 500 uCi/ml concentrations respectivelly. An observation was carried out to determines heredity of hopper sterilities from the mating groups of R male x N female, R male x R female, and N male x R female. The 32-P concentration below of 50 uCi/ml seemed to be the substerile dose, however, the dominant lethal mutation has been visually shown by R male x R female F1 mating group. The hereditary lines of F1, F2, F3, and F4 of the hopper sterilities wich were indicated by the nympha hatch ability have some significant correlations (r1= -0.77, r2= -0.92, r3= -0.93 and r4= -0.85). Thus, the resesif lethal mutations visually showed by F3 and F4 from all of the 100 uCi/ml and 50 uCi/ml treated groups. (author). 10 refs, 2 figs, 2 tabs

Lethal photosensitization of biofilm-grown bacteria

Science.gov (United States)

Wilson, Michael

1997-12-01

Antibacterial agents are increasingly being used for the prophylaxis and treatment of oral diseases. As these agents can be rendered ineffective by resistance development in the target organisms there is a need to develop alternative antimicrobial approaches. Light-activated antimicrobial agents release singlet oxygen and free radicals which can kill adjacent bacteria and a wide range of cariogenic and periodontopathogenic bacteria has been shown to be susceptible to such agents. In the oral cavity these organisms are present as biofilms (dental plaques) which are less susceptible to traditional antimicrobial agents than bacterial suspensions. The results of these studies have shown that biofilm-grown oral bacteria are also susceptible to lethal photosensitization although the light energy doses required are grater than those needed to kill the organisms when they are grown as aqueous suspensions.

Sub-lethal effects of neonicitinoids on the alfalfa leafcutter bee, Megachile rotundata

Science.gov (United States)

Neonicotinoids are commonly used pesticides in U.S. agriculture. For many beneficial insect species, lethal effects of neonicotinoids are well-documented; however, much less is known about sublethal exposure. The alfalfa leaf cutter bee Megachile rotundata is a managed pollinator that constructs com...

The Slimeball: The Development of Broad-Scale Maritime Non-Lethal Weaponry

Science.gov (United States)

2009-04-01

commercial applications from waste management to horticulture to baby diapers. By some estimates, it can absorb one thousand times its volume in water...www.nytimes.com/2008/10/31/world/africa/31pirates.html?pagewanted=1&_r=1. Goolsby, Tommy D. “Aqueous Foam as a Less-Than-Lethal Technology for Prison

Molecular basis of the mutagenic and lethal effects of ultraviolet irradiation

International Nuclear Information System (INIS)

Grossman, L.

1982-01-01

Using bacteria as a model, the molecular basis of the mutagenic and lethal effects of uv radiation is being studied. Attention is focused on the mechanism of action of uv-1 specific endonucleases in the repair of damaged DNA. The isolation and identification of similar enzymes in human cells are being conducted concurrently

Control of lethal browning by using ascorbic acid on shoot tip ...

African Journals Online (AJOL)

The use of ascorbic acid during explants preparation and the effect of different concentrations of ascorbic acid in controlling lethal browning and survival of the explants in local banana cv. Mzuzu banana were investigated. The explants were taken from young suckers. The shoot tips were cultured on Murashige and Skoog's ...

Relationship of Non-Structural Forms of Social Interaction with Problems of Social and Psychological Adaptation of Students Prone to Chemical Addictions

Science.gov (United States)

Gilemkhanova, Elvira N.

2016-01-01

The changes in contemporary social and cultural environment determine the necessity to increase the efficiency of adaptive mechanisms, especially for those categories of people who are subject to social risks. One of those categories is students prone to chemical addictions. To study the relationship of forms of social interaction with problems of…

Torrance type of lethal neonatal short-limbed platyspondylic dwarfism

International Nuclear Information System (INIS)

Kaibara, N.; Yokoyama, K.; Nakano, H.

1983-01-01

A rare case of lethal neonatal short-limbed platyspondylic dwarfism is described. Roentgenographic features of this case, distinctly different from those of the classical thanatophoric dysplasia, are indistinguishable from the other three types of short-limbed platyspondylic dwarfism. Histologic features of the cartilage in this case are not very different from those of the Torrance type, but the presence of focal disruption of column formation in this case suggests a wider spectrum for this entity. (orig.)

Genome Replikin Count Predicts Increased Infectivity/Lethality of Viruses

OpenAIRE

Samuel Bogoch; Elenore S. Bogoch

2012-01-01

The genomes of all groups of viruses whose sequences are listed on Pubmed, specimens since 1918, analyzed by a software from Bioradar UK Ltd., contain Replikins which range in concentration from a Replikin Count (number of Replikins per 100 amino acids) of less than 1 to 30 (see accompanying communications for higher Counts in tuberculosis, malaria, and cancer, associated with higher lethality). Counts of less than 4.0 were found in ‘resting’ virus states; Counts greater than 4....

Lethal and mutagenic effects of ion beams and γ-rays in Aspergillus oryzae

International Nuclear Information System (INIS)

Toyoshima, Yoshiyuki; Takahashi, Akemi; Tanaka, Hisaki; Watanabe, Jun; Mogi, Yoshinobu; Yamazaki, Tatsuo; Hamada, Ryoko; Iwashita, Kazuhiro; Satoh, Katsuya; Narumi, Issay

2012-01-01

Highlights: ► We investigated the effects of different LET radiation in A. oryzae. ► Both γ-rays and ion beams induced base substitutions, frameshifts, deletions. ► Both γ-rays and ion beams induced genome-wide large-scale mutations in A. oryzae. ► Some differences in the types and frequencies of mutations were found. ► Our results provide new basic insights into the mutation breeding of A. oryzae. - Abstract: Aspergillus oryzae is a fungus that is used widely in traditional Japanese fermentation industries. In this study, the lethal and mutagenic effects of different linear energy transfer (LET) radiation in freeze-dried conidia of A. oryzae were investigated. The lethal effect, which was evaluated by a 90% lethal dose, was dependent on the LET value of the ionizing radiation. The most lethal ionizing radiation among that tested was 12 C 5+ ion beams with an LET of 121 keV/μm. The 12 C 5+ ion beams had a 3.6-times higher lethal effect than low-LET (0.2 keV/μm) γ-rays. The mutagenic effect was evaluated by the frequency of selenate resistant mutants. 12 C 6+ ion beams with an LET of 86 keV/μm were the most effective in inducing selenate resistance. The mutant frequency following exposure to 12 C 6+ ion beams increased with an increase in dose and reached 3.47 × 10 −3 at 700 Gy. In the dose range from 0 to 700 Gy, 12 C 5+ ion beams were the second most effective in inducing selenate resistance, the mutant frequency of which reached a maximum peak (1.67 × 10 −3 ) at 400 Gy. To elucidate the characteristics of mutation induced by ionizing radiation, mutations in the sulphate permease gene (sB) and ATP sulfurylase gene (sC) loci, the loss of function of which results in a selenate resistant phenotype, were compared between 12 C 5+ ion beams and γ-rays. We detected all types of transversions and transitions. For frameshifts, the frequency of a +1 frameshift was the highest in all cases. Although the incidence of deletions >2 bp was generally low

First diagnosed lethal case of lyssavirus infection in Primorsky krai

OpenAIRE

Leonova, G.; Chentsova, I.; Petukhova, S.; Somova, L.; Belikov, S.; Kondratov, I.; Kryilova, N.; Plekhova, N.; Pavlenko, E.; Romanova, E.; Matsak, V.; Smirnov, G.; Novikov, D.

2010-01-01

The paper provides data of comprehensive study of lethal case of lyssavirus infection first diagnosed in Yakovlevsky municipal district in Primorsky Krai. The data of epidemiologic analysis (contact with a rattle mouse), clinical picture and results of virologic, morphological and molecular genetic tests allow attributing this case to lyssavirus infection. This is the first diagnosed case of lyssavirus infection in the Siberia and Far East.

Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error.

Science.gov (United States)

Shipitsin, M; Small, C; Choudhury, S; Giladi, E; Friedlander, S; Nardone, J; Hussain, S; Hurley, A D; Ernst, C; Huang, Y E; Chang, H; Nifong, T P; Rimm, D L; Dunyak, J; Loda, M; Berman, D M; Blume-Jensen, P

2014-09-09

Key challenges of biopsy-based determination of prostate cancer aggressiveness include tumour heterogeneity, biopsy-sampling error, and variations in biopsy interpretation. The resulting uncertainty in risk assessment leads to significant overtreatment, with associated costs and morbidity. We developed a performance-based strategy to identify protein biomarkers predictive of prostate cancer aggressiveness and lethality regardless of biopsy-sampling variation. Prostatectomy samples from a large patient cohort with long follow-up were blindly assessed by expert pathologists who identified the tissue regions with the highest and lowest Gleason grade from each patient. To simulate biopsy-sampling error, a core from a high- and a low-Gleason area from each patient sample was used to generate a 'high' and a 'low' tumour microarray, respectively. Using a quantitative proteomics approach, we identified from 160 candidates 12 biomarkers that predicted prostate cancer aggressiveness (surgical Gleason and TNM stage) and lethal outcome robustly in both high- and low-Gleason areas. Conversely, a previously reported lethal outcome-predictive marker signature for prostatectomy tissue was unable to perform under circumstances of maximal sampling error. Our results have important implications for cancer biomarker discovery in general and development of a sampling error-resistant clinical biopsy test for prediction of prostate cancer aggressiveness.

Relationship between fat globule size and chemical and fatty acid composition of cow's milk in mid lactation

Directory of Open Access Journals (Sweden)

Cosima Scolozzi

2010-01-01

Full Text Available The milk in 57 Italian Fresian cows in mid lactation was analysed in order to define the relationship between some qualitative milk parameters and the size of milk fat globules. The study focused on the morphometric evaluation of milk fat globules, chemical parameteres and fatty acid composition of the milk. The results show that a prevalence of milk fat globules with a diameter 6 um was associated (P<0.01 with greater milk yield nad a higher percentage of lactose, non-fat dry matter and ash............

Relationship between fat globule size and chemical and fatty acid composition of cow's milk in mid lactation

Directory of Open Access Journals (Sweden)

Mina Martini

2006-01-01

Full Text Available The milk in 57 Italian Fresian cows in mid lactation was analysed in order to define the relationship between some qualitative milk parameters and the size of milk fat globules. The study focused on the morphometric evaluation of milk fat globules, chemical parameteres and fatty acid composition of the milk. The results show that a prevalence of milk fat globules with a diameter 6 um was associated (P<0.01 with greater milk yield nad a higher percentage of lactose, non-fat dry matter and ash............

Proposals for chemical weapons during the American Civil War.

Science.gov (United States)

Hasegawa, Guy R

2008-05-01

Proposals for chemical weapons that arose during the American Civil War are described. Most incendiary and all biological agents are excluded. The described proposals appeared primarily in periodicals or letters to government officials on both sides. The weapons were usually meant to temporarily disable enemy combatants, but some might have been lethal, and Civil War caregivers were ill-prepared to deal with the weapons' effects. Evidently, none of the proposed weapons were used. In only one instance was use against civilians mentioned. Among the agents most commonly proposed were cayenne pepper or other plant-based irritants such as black pepper, snuff, mustard, and veratria. Other suggested agents included chloroform, chlorine, hydrogen cyanide, arsenic compounds, sulfur, and acids. Proponents usually suggested that the chemicals be included in explosive artillery projectiles. Less commonly proposed vehicles of delivery included fire engines, kites, and manned balloons. Some of the proposed weapons have modern counterparts.

Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities

International Nuclear Information System (INIS)

Peters, Diane E.; Hoover, Benjamin; Cloud, Loretta Grey; Liu, Shihui; Molinolo, Alfredo A.; Leppla, Stephen H.; Bugge, Thomas H.

2014-01-01

We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5–3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. - Highlights: • Toxicity and anti

Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities

Energy Technology Data Exchange (ETDEWEB)

Peters, Diane E. [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Program of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA (United States); Hoover, Benjamin [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Cloud, Loretta Grey [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Liu, Shihui [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Molinolo, Alfredo A. [Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Leppla, Stephen H. [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Bugge, Thomas H., E-mail: thomas.bugge@nih.go [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States)

2014-09-01

We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5–3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. - Highlights: • Toxicity and anti

Late radiation effects in animals surviving lethal irradiation

Energy Technology Data Exchange (ETDEWEB)

Dimitrov, L A

1974-01-01

Animals (rats, mice, dogs) survived lethal irradiation by means of prophylactic-therapeutic treatments or previously irradiated, were studied for late radiation effects: life span, cachexia and fat growing of hypophysical type, tissue or organ hypoplasia manifested by disturbed hemopoiesis, suppressed function of adrenal gland, etc., suppressed immune reactivity of the irradiated organism, atypical biochemical changes in DNA and protein metabolism, epilation, chronic dermatitis, ulcerations, reduced reproductivity or full sterility, damage of kidneys leading to nephrosclerosis, dishormonal states, cataracts, diffuse sclerotic processes, various kinds of malignant and non-malignant tumors. In these cases hemopoiesis compensated for a definite time peripheral blood composition, but during the late period it showed features of incompleteness: shorter life survival of erythrocytes and thrombocytes manifested by a decreased binding of labelled methionine in these blood elements, anemia and relative thrombocytopenia sometimes with an increased number of polychromatic erythrocytes in peripheral blood and a decreased number of reticulocytes at the same time; lymphopenia and relative leucopenia with an increased number of hypersegmented neutrophils. Decreased reproductivity and atypical biochemical changes available in the first generation of the irradiated animals showed the probable role of mutagenic factors in the emergency of some late radiation effects. A significant part of late radiation sequences were due to neuro-endocrine disintegrations. Some of the described late radiation effects were also observed in biological controls as features of ageing. After application of radioprotectors (AET, cysteamine, serotonin) a more marked protective effect is demonstrated in the early reactions (time survival till 30th day, DNA and protein metabolism, immune reactions) of the lethally irradiated animals.

1H NMR metabolomics of earthworm exposure to sub-lethal concentrations of phenanthrene in soil

International Nuclear Information System (INIS)

Brown, Sarah A.E.; McKelvie, Jennifer R.; Simpson, Andre J.; Simpson, Myrna J.

2010-01-01

1 H NMR metabolomics was used to monitor earthworm responses to sub-lethal (50-1500 mg/kg) phenanthrene exposure in soil. Total phenanthrene was analyzed via soxhlet extraction, bioavailable phenanthrene was estimated by hydroxypropyl-β-cyclodextrin (HPCD) and 1-butanol extractions and sorption to soil was assessed by batch equilibration. Bioavailable phenanthrene (HPCD-extracted) comprised ∼65-97% of total phenanthrene added to the soil. Principal component analysis (PCA) showed differences in responses between exposed earthworms and controls after 48 h exposure. The metabolites that varied with exposure included amino acids (isoleucine, alanine and glutamine) and maltose. PLS models indicated that earthworm response is positively correlated to both total phenanthrene concentration and bioavailable (HPCD-extracted) phenanthrene in a freshly spiked, unaged soil. These results show that metabolomics is a powerful, direct technique that may be used to monitor contaminant bioavailability and toxicity of sub-lethal concentrations of contaminants in the environment. These initial findings warrant further metabolomic studies with aged contaminated soils. - 1 H NMR metabolomics is used to directly monitor metabolic responses of Eisenia fetida after 48 h of exposure to sub-lethal concentrations of phenanthrene in soil.

Hormone-dependence of sarin lethality in rats: Sex differences and stage of the estrous cycle

Energy Technology Data Exchange (ETDEWEB)

Smith, Carl D., E-mail: carl.d.smith179.mil@mail.mil; Wright, Linnzi K.M.; Garcia, Gregory E.; Lee, Robyn B.; Lumley, Lucille A.

2015-09-15

Chemical warfare nerve agents (CWNAs) are highly toxic compounds that cause a cascade of symptoms and death, if exposed casualties are left untreated. Numerous rodent models have investigated the toxicity and mechanisms of toxicity of CWNAs, but most are limited to male subjects. Given the profound physiological effects of circulating gonadal hormones in female rodents, it is possible that the daily cyclical fluctuations of these hormones affect females' sensitivity to the lethal effects of CWNAs, and previous reports that included female subjects did not control for the stage of the hormonal cycle. The aim of the current study was to determine the 24-hour median lethal dose (LD{sub 50}) of the CWNA sarin in male, ovariectomized (OVEX) female, and female rats during different stages of the estrous cycle (diestrus, proestrus, and estrus). Additionally, baseline activity levels of plasma acetylcholinesterase, butyrylcholinesterase, and carboxylesterase were measured to determine differences among the groups. Results indicated that females in proestrus had a significantly higher LD{sub 50} of sarin compared to OVEX and estrous females. Although some sex differences were observed in the activity levels of plasma esterases, they were not consistent and likely not large enough to significantly affect the LD{sub 50}s. These results suggest that hormonal cyclicity can influence the outcome of CWNA-related studies using female rodents, and that this variability can be minimized by controlling for the stage of the cycle. Additional research is necessary to determine the precise mechanism of the observed differences because it is unlikely to be solely explained by plasma esterase activity. - Highlights: • The LD{sub 50} of sarin was determined in female rats throughout the stages of the estrous cycle. • Females in proestrus had a significantly higher LD{sub 50} compared to estrous or ovariectomized females. • No sex differences were observed between male and female

Crowd Behavior, Crowd Control, and the Use of Non-Lethal Weapons

Science.gov (United States)

2001-01-01

that U.S. forces know these repertoires of actions when they operate in different cultures. Dr. Waddington provided the example of the Zulu tribe in...6 The History of Hostile Crowds and Riots...Mobs, and Non-lethal Weapons,” by Lieutenant Sid Heal. The History of Hostile Crowds and Riots Dr. Wendy Gilpin conducted background research on hostile

Relationship Between the Dose-Response Curves for Lethality and Severe Effects for Chemical Warfare Nerve Agents

National Research Council Canada - National Science Library

Sommerville, Douglas R

2005-01-01

... (involving acute inhalation exposures to G-type nerve agents) were reviewed and analyzed. For all three studies, slightly more than one standard deviation separated an effective concentration (ECxx...

Comparative toxicity of chemicals to earthworms

Energy Technology Data Exchange (ETDEWEB)

Callahan, C.A.; Shirazi, M.A. (Environmental Protection Agency, Corvallis, OR (United States)); Neuhauser, E.F. (Niagara Mohawk Power Corp., Syracuse, NY (United States))

1994-02-01

The concentration-response (mortality) relationships of four species of earthworms, Eisenia fetida (Savigny), Allolobophora tuberculata (Eisen), Eudrilus eugeniae (Kinberg), and Perionyx excavatus (Perrier) are summarized for 62 chemicals and two test protocols. A Weibull function is used to summarize these data for each chemical in terms of sensitivity and toxicity, in addition to the LC50. The estimation of the Weibull parameters a and k summarize the entire concentration-response relationship. This technique should be applicable to a variety of testing protocols with different species whenever the goal is summarizing the shape of the concentration-response curves to fully evaluate chemical impact on organisms. In some cases for these data four orders of magnitude separate LC50s of the soil test and the contact test for the same chemical and species. All four species appear to be similar in range of toxicity and tolerance to these chemicals, suggesting that Eisenia fetida and may be representative of these four species and these chemicals.

When Suicide Kills: An Empirical Analysis of the Lethality of Suicide Terrorism

Directory of Open Access Journals (Sweden)

Burcu Pinar Alakoc

2017-12-01

Full Text Available Why are some suicide terrorist attacks deadlier than others? Suicide bombers, unlike stationary bombs, are self-guided human weapons; they can deliver and detonate explosives at a specific time and place with precision. Coding and analyzing new data on over four hundred suicide terrorist incidents from all around the world between 1998 and 2015, this paper argues that the number of fatalities resulting from suicide attacks is a function of strategic choices made by the perpetrators, such as where to attack and whom to target. Results of this analysis show that suicide attacks that seize targets of opportunity are the most lethal. Specifically, suicide attacks that target civilians in enclosed and easily accessible places, and that are undertaken by multiple perpetrators result in the highest numbers of fatalities. Understanding these strategic tactical attributes of suicide terrorism is fundamental to devising effective counterterrorism strategies that aim at hardening soft targets and minimizing the lethal impact of these attacks.

Points of Influence for Lethal Means Counseling and Safe Gun Storage Practices.

Science.gov (United States)

Runyan, Carol W; Brooks-Russell, Ashley; Betz, Marian E

2018-06-07

Counseling about reducing access to lethal means of suicide, especially firearms, is a recommended practice in emergency departments (EDs) but does not occur routinely. Understanding influencers of decisions makers in health care (ED nurse leaders, mental health providers) and temporary firearm storage (law enforcement and gun retailers) could enhance practice. We surveyed these 4 groups in the 8-state region of the Mountain West. For ED nurse leaders (n = 190), hospital legal, risk management, and quality improvement representatives, and the ED nursing director were most often cited as influential, whereas mental health providers (n = 67) cited their own team. Law enforcement officials (n = 448) identified the overall community and leaders of mental health or general health organizations as influential. Firearm retailers (n = 95) cited local law enforcement and national firearm organizations. Advocacy from influential groups may encourage efforts to provide lethal means counseling and temporary off-site storage of firearms for suicide prevention.

Ants defend aphids against lethal disease

Science.gov (United States)

Nielsen, Charlotte; Agrawal, Anurag A.; Hajek, Ann E.

2010-01-01

Social insects defend their own colonies and some species also protect their mutualist partners. In mutualisms with aphids, ants typically feed on honeydew produced by aphids and, in turn guard and shelter aphid colonies from insect natural enemies. Here we report that Formica podzolica ants tending milkweed aphids, Aphis asclepiadis, protect aphid colonies from lethal fungal infections caused by an obligate aphid pathogen, Pandora neoaphidis. In field experiments, bodies of fungal-killed aphids were quickly removed from ant-tended aphid colonies. Ant workers were also able to detect infective conidia on the cuticle of living aphids and responded by either removing or grooming these aphids. Our results extend the long-standing view of ants as mutualists and protectors of aphids by demonstrating focused sanitizing and quarantining behaviour that may lead to reduced disease transmission in aphid colonies. PMID:19923138

Gluconeogenesis in lethally X-irradiated rats

International Nuclear Information System (INIS)

Paulikova, E.; Ahlers, I.; Praslicka, M.

1983-01-01

The in vivo incorporation of U- 14 C-alanine into blood glucose and liver glycogen was measured in rats irradiated with a single whole body lethal dose of X-rays. Changes in gluconeogenic enzyme activities were studied in the liver. Increased incorporation of 14 C-alanine into blood glucose and liver glycogen were found after irradiation. Liver phosphoenolpyruvate carboxykinase and glycogenic activity underwent almost parallel changes and were significantly elevated from the 6th to the 48th hour, with resultant accumulation of glycogen. Glucose-6-phosphatase activity was depressed and there was a negative correlation between it and liver glycogen concentration. Maximum fructose-1,6-diphosphatase activity was found at 48 hours. The results show that glycogen accumulation in the liver and the raised blood glucose level in X-irradiated rats are based on raised gluconeogenesis. (author)

Gluconeogenesis in lethally X-irradiated rats

Energy Technology Data Exchange (ETDEWEB)

Paulikova, E.; Ahlers, I.; Praslicka, M. (Univerzita P.J. Safarika, Kosice (Czechoslovakia). Katedra Vseobecnej Biologie)

1983-02-01

The in vivo incorporation of U-/sup 14/C-alanine into blood glucose and liver glycogen was measured in rats irradiated with a single whole body lethal dose of X-rays. Changes in gluconeogenic enzyme activities were studied in the liver. Increased incorporation of /sup 14/C-alanine into blood glucose and liver glycogen were found after irradiation. Liver phosphoenolpyruvate carboxykinase and glycogenic activity underwent almost parallel changes and were significantly elevated from the 6th to the 48th hour, with resultant accumulation of glycogen. Glucose-6-phosphatase activity was depressed and there was a negative correlation between it and liver glycogen concentration. Maximum fructose-1,6-diphosphatase activity was found at 48 hours. The results show that glycogen accumulation in the liver and the raised blood glucose level in X-irradiated rats are based on raised gluconeogenesis.

Recurrent late cardiac tamponade following cardiac surgery : a deceiving and potentially lethal complication

NARCIS (Netherlands)

Harskamp, Ralf E.; Meuzelaar, Jacobus J.

2010-01-01

Background - Cardiac tamponade, characterized by inflow obstruction of the heart chambers by extracardiac compression, is a potentially lethal complication following cardiac surgery. Case report - We present a case of recurrent cardiac tamponade following valve surgery. At first presentation,

Guidance on health effects of toxic chemicals. Safety Analysis Report Update Program

Energy Technology Data Exchange (ETDEWEB)

Foust, C.B.; Griffin, G.D.; Munro, N.B.; Socolof, M.L.

1994-02-01

Martin Marietta Energy Systems, Inc. (MMES), and Martin Marietta Utility Services, Inc. (MMUS), are engaged in phased programs to update the safety documentation for the existing US Department of Energy (DOE)-owned facilities. The safety analysis of potential toxic hazards requires a methodology for evaluating human health effects of predicted toxic exposures. This report provides a consistent set of health effects and documents toxicity estimates corresponding to these health effects for some of the more important chemicals found within MMES and MMUS. The estimates are based on published toxicity information and apply to acute exposures for an ``average`` individual. The health effects (toxicological endpoints) used in this report are (1) the detection threshold; (2) the no-observed adverse effect level; (3) the onset of irritation/reversible effects; (4) the onset of irreversible effects; and (5) a lethal exposure, defined to be the 50% lethal level. An irreversible effect is defined as a significant effect on a person`s quality of life, e.g., serious injury. Predicted consequences are evaluated on the basis of concentration and exposure time.

Crowd Confrontation and Non-Lethal Weapons: A Literature Review and Conceptual Model

Science.gov (United States)

2008-03-01

counterterrorist situations, when there is a need to incapacitate one or several terrorists operating from within a larger group of harmless individuals. In such...weapons include some microbes capable of degrading fuel, an herbicide (“Agent Orange”), as well as non-lethal anti-personnel mines. It is concluded

Relationship between bacterial density and chemical composition of ...

African Journals Online (AJOL)

TUOYO

Key words: Bacterial density, chemical composition, oxidation pond, sewage, tropics. INTRODUCTION ... pond for about two weeks during which algae, bacteria and other organisms act ..... Chloride can serve as nutrient for micro- organisms ...

Lethal Means Counseling for Parents of Youth Seeking Emergency Care for Suicidality

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Carol W. Runyan, MPH, PhD

2016-01-01

Full Text Available Introduction: A youth’s emergency department (ED visit for suicidal behaviors or ideation provides an opportunity to counsel families about securing medications and firearms (i.e., lethal means counseling. Methods: In this quality improvement project drawing on the Counseling on Access to Lethal Means (CALM model, we trained 16 psychiatric emergency clinicians to provide lethal means counseling with parents of patients under age 18 receiving care for suicidality and discharged home from a large children’s hospital. Through chart reviews and follow-up interviews of parents who received the counseling, we examined what parents recalled, their reactions to the counseling session, and actions taken after discharge. Results: Between March and July 2014, staff counseled 209 of the 236 (89% parents of eligible patients. We conducted follow-up interviews with 114 parents, or 55% of those receiving the intervention; 48% of those eligible. Parents had favorable impressions of the counseling and good recall of the main messages. Among the parents contacted at follow up, 76% reported all medications in the home were locked as compared to fewer than 10% at the time of the visit. All who had indicated there were guns in the home at the time of the visit reported at follow up that all were currently locked, compared to 67% reporting this at the time of the visit. Conclusion: Though a small project in just one hospital, our findings demonstrate the feasibility of adding a counseling protocol to the discharge process within a pediatric psychiatric emergency service. Our positive findings suggest that further study, including a randomized control trial in more facilities, is warranted.

hERG trafficking inhibition in drug-induced lethal cardiac arrhythmia.

Science.gov (United States)

Nogawa, Hisashi; Kawai, Tomoyuki

2014-10-15

Acquired long QT syndrome induced by non-cardiovascular drugs can cause lethal cardiac arrhythmia called torsades de points and is a significant problem in drug development. The prolongation of QT interval and cardiac action potential duration are mainly due to reduced physiological function of the rapidly activating voltage-dependent potassium channels encoded by human ether-a-go-go-related gene (hERG). Structurally diverse groups of drugs are known to directly inhibit hERG channel conductance. Therefore, the ability of acute hERG inhibition is routinely assessed at the preclinical stages in pharmaceutical testing. Recent findings indicated that chronic treatment with various drugs not only inhibits hERG channels but also decreases hERG channel expression in the plasma membrane of cardiomyocytes, which has become another concern in safety pharmacology. The mechanisms involve the disruption of hERG trafficking to the surface membrane or the acceleration of hERG protein degradation. From this perspective, we present a brief overview of mechanisms of drug-induced trafficking inhibition and pathological regulation. Understanding of drug-induced hERG trafficking inhibition may provide new strategies for predicting drug-induced QT prolongation and lethal cardiac arrhythmia in pharmaceutical drug development. Copyright © 2014 Elsevier B.V. All rights reserved.

Using Simulation to Increase Yields in Chemical Engineering

Directory of Open Access Journals (Sweden)

William C. Conley

2003-06-01

Full Text Available Trying to increase the yields or profit or efficiency (less pollution of chemical processes is a central goal of the chemical engineer in theory and practice. Certainly sound training in chemistry, business and pollution control help the engineer to set up optimal chemical processes. However, the ever changing demands of customers and business conditions, plus the multivariate complexity of the chemical business can make optimization challenging. Mathematical tools such as statistics and linear programming have certainly been useful to chemical engineers in their pursuit of optimal efficiency. However, some processes can be modeled linearly and some can not. Therefore, presented here will be an industrial chemical process with potentially five variables affecting the yield. Data from over one hundred runs of the process has been collected, but it is not known initially whether the yield relationship is linear or nonlinear. Therefore, the CTSP multivariate correlation coefficient will be calculated for the data to see if a relationship exists among the variables. Then once it is proven that there is a statistically significant relationship, an appropriate linear or nonlinear equation can be fitted to the data, and it can be optimized for use in the chemical plant.

Quantitative structure-activity relationships for predicting potential ecological hazard of organic chemicals for use in regulatory risk assessments.

Science.gov (United States)

Comber, Mike H I; Walker, John D; Watts, Chris; Hermens, Joop

2003-08-01

The use of quantitative structure-activity relationships (QSARs) for deriving the predicted no-effect concentration of discrete organic chemicals for the purposes of conducting a regulatory risk assessment in Europe and the United States is described. In the United States, under the Toxic Substances Control Act (TSCA), the TSCA Interagency Testing Committee and the U.S. Environmental Protection Agency (U.S. EPA) use SARs to estimate the hazards of existing and new chemicals. Within the Existing Substances Regulation in Europe, QSARs may be used for data evaluation, test strategy indications, and the identification and filling of data gaps. To illustrate where and when QSARs may be useful and when their use is more problematic, an example, methyl tertiary-butyl ether (MTBE), is given and the predicted and experimental data are compared. Improvements needed for new QSARs and tools for developing and using QSARs are discussed.

The distribution of and complementation relationships between spontaneous X-linked recessive lethal mutations recovered from crossing long-term laboratory stocks of Drosophila melanogaster

International Nuclear Information System (INIS)

Schalet, A.P.

1986-01-01

Drosophila melanogaster males from a wild-type laboratory stock, were mated with virgin females of the M-6 stock, and 149 spontaneous independent non-mosaically transmitted, as well as 8 incidentally detected, mosaically transmitted, X-linked recessive lethal mutations were recovered from 95 704 F 2 cultures. 152 mutations were mapped over the entire length of the X-chromosome by complementation and/or crossover tests. Although there were far too few spontaneous mutations to make a meaningful comparison of relative mutability on a locus-by-locus basis, those loci displaying a relatively higher X-ray mutability, when taken as a group, tend to display a relatively higher spontaneous mutability, and those loci displaying a relatively lower X-ray mutability, when taken as a group, tend to display a relatively lower spontaneous mutability. (Auth.)

Lethal and Sublethal Effects of Insecticides Used on Citrus, on the Ectoparasitoid Tamarixia radiata.

Science.gov (United States)

Beloti, Vitor Hugo; Alves, Gustavo Rodrigues; Araújo, Diogo Feliciano Dias; Picoli, Mateus Manara; Moral, Rafael de Andrade; Demétrio, Clarice Garcia Borges; Yamamoto, Pedro Takao

2015-01-01

Huanglongbing (HLB) is a disease associated with the bacteria "Candidatus Liberibacter spp." and has been devastating citrus orchards around the world. Its management involves control of the insect vector, the Asian citrus psyllid Diaphorina citri Kuwayama. However, the indiscriminate use of chemicals has caused pest outbreaks and eliminated the natural enemies of the vector, such as the parasitoid Tamarixia radiata (Waterston), the main agent for biological control of D. citri. This study assessed the lethal and sublethal effects of insecticides recommended for integrated production of citrus on the parasitoid T. radiata. When adult parasitoids were exposed to residues of 25 insecticides, 20% of them, i.e., gamma-cyhalothrin, etofenprox, azadirachtin, tebufenozide and pyriproxyfen, were considered as harmless (Class 1), 12% as slightly harmful (Class 2), 12% as moderately harmful (Class 3) and 56% as harmful (Class 4), according to the classification proposed by the IOBC/WPRS. Afterward, 14 insecticides (5 harmless and 9 harmful) were sprayed on the parasitoid pupae. Of the 14 insecticides tested, only the organophosphates dimethoate and chlorpyrifos affected the parasitoid emergence. The effects of insecticides on the parasitism capacity of adults exposed to residues of azadirachtin, etofenprox, gamma-cyhalothrin, pyriproxyfen and tebufenozide (harmless) were also evaluated. Tebufenozide and gamma-cyhalothrin affected the parasitism of the F0 generation, but did not affect the emergence of the F1 and F2 generations. Therefore, for an effective IPM program, selective insecticides or harmful pesticides to adult parasitoids could be used in the field, provided that the adults do not occur naturally and the chemical applications do not coincide with parasitoid releases.

Lethal and Sublethal Effects of Insecticides Used on Citrus, on the Ectoparasitoid Tamarixia radiata.

Directory of Open Access Journals (Sweden)

Vitor Hugo Beloti

Full Text Available Huanglongbing (HLB is a disease associated with the bacteria "Candidatus Liberibacter spp." and has been devastating citrus orchards around the world. Its management involves control of the insect vector, the Asian citrus psyllid Diaphorina citri Kuwayama. However, the indiscriminate use of chemicals has caused pest outbreaks and eliminated the natural enemies of the vector, such as the parasitoid Tamarixia radiata (Waterston, the main agent for biological control of D. citri. This study assessed the lethal and sublethal effects of insecticides recommended for integrated production of citrus on the parasitoid T. radiata. When adult parasitoids were exposed to residues of 25 insecticides, 20% of them, i.e., gamma-cyhalothrin, etofenprox, azadirachtin, tebufenozide and pyriproxyfen, were considered as harmless (Class 1, 12% as slightly harmful (Class 2, 12% as moderately harmful (Class 3 and 56% as harmful (Class 4, according to the classification proposed by the IOBC/WPRS. Afterward, 14 insecticides (5 harmless and 9 harmful were sprayed on the parasitoid pupae. Of the 14 insecticides tested, only the organophosphates dimethoate and chlorpyrifos affected the parasitoid emergence. The effects of insecticides on the parasitism capacity of adults exposed to residues of azadirachtin, etofenprox, gamma-cyhalothrin, pyriproxyfen and tebufenozide (harmless were also evaluated. Tebufenozide and gamma-cyhalothrin affected the parasitism of the F0 generation, but did not affect the emergence of the F1 and F2 generations. Therefore, for an effective IPM program, selective insecticides or harmful pesticides to adult parasitoids could be used in the field, provided that the adults do not occur naturally and the chemical applications do not coincide with parasitoid releases.

Proteomic characterization of a temperature-sensitive conditional lethal in Drosophila melanogaster

DEFF Research Database (Denmark)

Pedersen, Kamilla Sofie; Codrea, M.C; Vermeulen, Corneel

2010-01-01

Genetic variation that is expressed only under specific environmental conditions can contribute to additional adverse effects of inbreeding if environmental conditions change. We present a proteomic characterization of a conditional lethal found in an inbred line of Drosophila melanogaster. The l...

Recurrent late cardiac tamponade following cardiac surgery: a deceiving and potentially lethal complication

NARCIS (Netherlands)

Harskamp, Ralf E.; Meuzelaar, Jacobus J.

2010-01-01

Cardiac tamponade, characterized by inflow obstruction of the heart chambers by extracardiac compression, is a potentially lethal complication following cardiac surgery. We present a case of recurrent cardiac tamponade following valve surgery. At first presentation, diagnosis was delayed because of

Chemical toxicity approach for emergency response

International Nuclear Information System (INIS)

Bauer, T.

2009-01-01

In the event of an airborne release of chemical agent or toxic industrial chemical by accidental or intentional means, emergency responders must have a reasonable estimate of the location and size of the resulting hazard area. Emergency responders are responsible for warning persons downwind of the hazard to evacuate or shelter-in-place and must know where to look for casualties after the hazard has passed or dissipated. Given the same source characterization, modern hazard assessment models provide comparable concentration versus location and time estimates. Even urban hazard assessment models often provide similar predictions. There is a major shortcoming, though, in applying model output to estimating human toxicity effects. There exist a variety of toxicity values for non-lethal effects ranging from short-term to occupational to lifetime exposures. For health and safety purposes, these estimates are all safe-sided in converting animal data to human effects and in addressing the most sensitive subset of the population. In addition, these values are usually based on an assumed 1 hour exposure duration at constant concentration and do not reflect either a passing clouds concentration profile or duration. Emergency responders need expected value toxicity parameters rather than the existing safe-sided ones. This presentation will specify the types of toxicity values needed to provide appropriate chemical hazard estimates to emergency responders and will demonstrate how dramatically their use changes the hazard area.(author)

Effect of salinity on the upper lethal temperature tolerance of early-juvenile red drum.

Science.gov (United States)

McDonald, Dusty; Bumguardner, Britt; Cason, Paul

2015-10-01

Previous work investigating the temperature tolerance of juvenile red drum ranging 18-50mm TL found evidence for positive size dependence (smaller fish less tolerant to higher temperatures) suggesting smaller size classes (temperatures. Here, we explored the upper lethal temperature tolerance (ULT) in smaller-sized red drum which ranged from 10 to 20mm TL across multiple salinities to further understand the thermal limitations of this propagated game fish. In order to investigate the combined effect of temperature and salinity on ULT, temperature trials were conducted under three levels of salinity which commonly occur along the coast of Texas (25, 35, and 45ppt). The rate of temperature increase (+0.25°C/h) was designed to mimic a natural temperature increase of a summer day in Texas. We determined that the lethal temperature at 50% (LT50) did not differ between the three salinities examined statistically; median lethal temperature for individuals exposed to 25ppt ranged from 36.4 to 37.7°C, 35ppt ranged from 36.4 to 37.7°C, and 45ppt ranged from 36.1 to 37.4°C. Further, LT50 data obtained here for early-juvenile red drum did not differ from data of a similar experiment examining 25mm TL sized fish. Published by Elsevier Ltd.

Lethal and mutagenic effects of ion beams and γ-rays in Aspergillus oryzae

Energy Technology Data Exchange (ETDEWEB)

Toyoshima, Yoshiyuki, E-mail: toyoshima@yamasa.com [Soy Sauce Laboratory, Yamasa Corporation, 2-10-1 Araoicho, Choshi, Chiba 288-0056 (Japan); Takahashi, Akemi; Tanaka, Hisaki; Watanabe, Jun; Mogi, Yoshinobu; Yamazaki, Tatsuo [Soy Sauce Laboratory, Yamasa Corporation, 2-10-1 Araoicho, Choshi, Chiba 288-0056 (Japan); Hamada, Ryoko; Iwashita, Kazuhiro [Fundamental Research Division, National Research Institute of Brewing, 3-7-1 Kagamiyama, Higashihiroshima, Hiroshima 739-0046 (Japan); Satoh, Katsuya; Narumi, Issay [Ion Beam Mutagenesis Research Group, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki, Takasaki, Gunma 370-1292 (Japan)

2012-12-15

Highlights: ► We investigated the effects of different LET radiation in A. oryzae. ► Both γ-rays and ion beams induced base substitutions, frameshifts, deletions. ► Both γ-rays and ion beams induced genome-wide large-scale mutations in A. oryzae. ► Some differences in the types and frequencies of mutations were found. ► Our results provide new basic insights into the mutation breeding of A. oryzae. - Abstract: Aspergillus oryzae is a fungus that is used widely in traditional Japanese fermentation industries. In this study, the lethal and mutagenic effects of different linear energy transfer (LET) radiation in freeze-dried conidia of A. oryzae were investigated. The lethal effect, which was evaluated by a 90% lethal dose, was dependent on the LET value of the ionizing radiation. The most lethal ionizing radiation among that tested was {sup 12}C{sup 5+} ion beams with an LET of 121 keV/μm. The {sup 12}C{sup 5+} ion beams had a 3.6-times higher lethal effect than low-LET (0.2 keV/μm) γ-rays. The mutagenic effect was evaluated by the frequency of selenate resistant mutants. {sup 12}C{sup 6+} ion beams with an LET of 86 keV/μm were the most effective in inducing selenate resistance. The mutant frequency following exposure to {sup 12}C{sup 6+} ion beams increased with an increase in dose and reached 3.47 × 10{sup −3} at 700 Gy. In the dose range from 0 to 700 Gy, {sup 12}C{sup 5+} ion beams were the second most effective in inducing selenate resistance, the mutant frequency of which reached a maximum peak (1.67 × 10{sup −3}) at 400 Gy. To elucidate the characteristics of mutation induced by ionizing radiation, mutations in the sulphate permease gene (sB) and ATP sulfurylase gene (sC) loci, the loss of function of which results in a selenate resistant phenotype, were compared between {sup 12}C{sup 5+} ion beams and γ-rays. We detected all types of transversions and transitions. For frameshifts, the frequency of a +1 frameshift was the highest in all

Soil physical properties regulate lethal heating during burning of woody residues

Science.gov (United States)

Matt Busse; Carol Shestak; Ken Hubbert; Eric Knapp

2010-01-01

Temperatures well in excess of the lethal threshold for roots (60°C) have been measured in forest soils when woody fuels are burned. Whether this heat pulse is strongly moderated by soil moisture or soil texture is not fully understood, however. We measured soil heat profi les during 60 experimental burns, identifying changes in maximum soil temperature and heat...

Clinical and symptomatological study of pigs subjected to a lethal dose of integral gamma irradiation

International Nuclear Information System (INIS)

Vaiman, M.; Guenet, J.-L.; Maas, J.; Nizza, P.

1966-05-01

Results are reported from a clinical and haematological study on a Corsican species of pigs wholly exposed to an approximately lethal dose of γ radiation. The aim of this work was to examine the changes in the irradiation syndrome of irradiation for pigs to make it thus possible to devise further experiments, in particular in the therapeutic field. The dose received was 285 rads (measured as the absorption in the vertical antero-posterior medial plane). Data are presented on cyto-haematological changes in the blood circulating immediately after irradiation, and followed up to death, and changes in the medullary cytology after irradiation. The clinical picture of lethal radiation injury in swine is described. (authors) [fr

A linear-quadratic model of cell survival considering both sublethal and potentially lethal radiation damage

International Nuclear Information System (INIS)

Rutz, H.P.; Coucke, P.A.; Mirimanoff, R.O.

1991-01-01

The authors assessed the dose-dependence of repair of potentially lethal damage in Chinese hamster ovary cells x-irradiated in vitro. The recovery ratio (RR) by which survival (SF) of the irradiated cells was enhanced increased exponentially with a linear and a quadratic component namely ζ and ψ: RR=exp(ζD+ψD 2 ). Survival of irradiated cells can thus be expressed by a combined linear-quadratic model considering 4 variables, namely α and β for the capacity of the cells to accumulate sublethal damage, and ζ and ψ for their capacity to repair potentially lethal damage: SF=exp((ζ-α)D+ (ψ-β)D 2 ). author. 26 refs.; 1 fig.; 1 tab

Comparative influence of dose rate and radiation nature, on lethality after big mammals irradiation

International Nuclear Information System (INIS)

Destombe, C.; Le Fleche, Ph.; Grasseau, A.; Reynal, A.

1997-01-01

For the same dose and the 30 days lethality as biological criterion, the dose rate influence is more important than the radiation nature on the results of an big mammals total body irradiation. (authors)

The effects of 'cell age' upon the lethal effects of physical and chemical mutagens in the yeast, Saccharomyces cerevisiae

International Nuclear Information System (INIS)

Parry, J.M.

1976-01-01

Yeast cultures progressing from the exponential to the stationary phase of growth showed changes in cell sensitivity to physical agents such as UV light, heat shock at 52 0 C and the chemical mutagens ethyl methane sulphonate, nitrous acid and mitomycin C. Exponential phase cells showed maximum resistance to heat shock and the three chemicals. The increased resistance of exponential phase cells to UV light was shown to be dependent upon the functional integrity of the RAD 50 gene. Treatment of growing yeast cultures with radioactively labelled ethyl methane sulphonate indicated the preferential uptake of radioactivity during the sensitive exponential stage of growth. The results indicated that the differential uptake of the chemical mutagens was responsible for at least a fraction of the variations in cell sensitivity observed in yeast cultures at different phases of growth. (orig.) [de

Adapted Lethality: What We Can Learn from Guinea Pig-Adapted Ebola Virus Infection Model.

Science.gov (United States)

Cheresiz, S V; Semenova, E A; Chepurnov, A A

2016-01-01

Establishment of small animal models of Ebola virus (EBOV) infection is important both for the study of genetic determinants involved in the complex pathology of EBOV disease and for the preliminary screening of antivirals, production of therapeutic heterologic immunoglobulins, and experimental vaccine development. Since the wild-type EBOV is avirulent in rodents, the adaptation series of passages in these animals are required for the virulence/lethality to emerge in these models. Here, we provide an overview of our several adaptation series in guinea pigs, which resulted in the establishment of guinea pig-adapted EBOV (GPA-EBOV) variants different in their characteristics, while uniformly lethal for the infected animals, and compare the virologic, genetic, pathomorphologic, and immunologic findings with those obtained in the adaptation experiments of the other research groups.

Adapted Lethality: What We Can Learn from Guinea Pig-Adapted Ebola Virus Infection Model

Directory of Open Access Journals (Sweden)

S. V. Cheresiz

2016-01-01

Full Text Available Establishment of small animal models of Ebola virus (EBOV infection is important both for the study of genetic determinants involved in the complex pathology of EBOV disease and for the preliminary screening of antivirals, production of therapeutic heterologic immunoglobulins, and experimental vaccine development. Since the wild-type EBOV is avirulent in rodents, the adaptation series of passages in these animals are required for the virulence/lethality to emerge in these models. Here, we provide an overview of our several adaptation series in guinea pigs, which resulted in the establishment of guinea pig-adapted EBOV (GPA-EBOV variants different in their characteristics, while uniformly lethal for the infected animals, and compare the virologic, genetic, pathomorphologic, and immunologic findings with those obtained in the adaptation experiments of the other research groups.

Synthetic lethality between gene defects affecting a single non-essential molecular pathway with reversible steps.

Directory of Open Access Journals (Sweden)

Andrei Zinovyev

2013-04-01

Full Text Available Systematic analysis of synthetic lethality (SL constitutes a critical tool for systems biology to decipher molecular pathways. The most accepted mechanistic explanation of SL is that the two genes function in parallel, mutually compensatory pathways, known as between-pathway SL. However, recent genome-wide analyses in yeast identified a significant number of within-pathway negative genetic interactions. The molecular mechanisms leading to within-pathway SL are not fully understood. Here, we propose a novel mechanism leading to within-pathway SL involving two genes functioning in a single non-essential pathway. This type of SL termed within-reversible-pathway SL involves reversible pathway steps, catalyzed by different enzymes in the forward and backward directions, and kinetic trapping of a potentially toxic intermediate. Experimental data with recombinational DNA repair genes validate the concept. Mathematical modeling recapitulates the possibility of kinetic trapping and revealed the potential contributions of synthetic, dosage-lethal interactions in such a genetic system as well as the possibility of within-pathway positive masking interactions. Analysis of yeast gene interaction and pathway data suggests broad applicability of this novel concept. These observations extend the canonical interpretation of synthetic-lethal or synthetic-sick interactions with direct implications to reconstruct molecular pathways and improve therapeutic approaches to diseases such as cancer.

Exome sequencing for gene discovery in lethal fetal disorders--harnessing the value of extreme phenotypes.

Science.gov (United States)

Filges, Isabel; Friedman, Jan M

2015-10-01

Massively parallel sequencing has revolutionized our understanding of Mendelian disorders, and many novel genes have been discovered to cause disease phenotypes when mutant. At the same time, next-generation sequencing approaches have enabled non-invasive prenatal testing of free fetal DNA in maternal blood. However, little attention has been paid to using whole exome and genome sequencing strategies for gene identification in fetal disorders that are lethal in utero, because they can appear to be sporadic and Mendelian inheritance may be missed. We present challenges and advantages of applying next-generation sequencing approaches to gene discovery in fetal malformation phenotypes and review recent successful discovery approaches. We discuss the implication and significance of recessive inheritance and cross-species phenotyping in fetal lethal conditions. Whole exome sequencing can be used in individual families with undiagnosed lethal congenital anomaly syndromes to discover causal mutations, provided that prior to data analysis, the fetal phenotype can be correlated to a particular developmental pathway in embryogenesis. Cross-species phenotyping allows providing further evidence for causality of discovered variants in genes involved in those extremely rare phenotypes and will increase our knowledge about normal and abnormal human developmental processes. Ultimately, families will benefit from the option of early prenatal diagnosis. © 2014 John Wiley & Sons, Ltd.

Deciphering the Mechanisms of Developmental Disorders (DMDD: a new programme for phenotyping embryonic lethal mice

Directory of Open Access Journals (Sweden)

Timothy Mohun

2013-05-01

International efforts to test gene function in the mouse by the systematic knockout of each gene are creating many lines in which embryonic development is compromised. These homozygous lethal mutants represent a potential treasure trove for the biomedical community. Developmental biologists could exploit them in their studies of tissue differentiation and organogenesis; for clinical researchers they offer a powerful resource for investigating the origins of developmental diseases that affect newborns. Here, we outline a new programme of research in the UK aiming to kick-start research with embryonic lethal mouse lines. The ‘Deciphering the Mechanisms of Developmental Disorders’ (DMDD programme has the ambitious goal of identifying all embryonic lethal knockout lines made in the UK over the next 5 years, and will use a combination of comprehensive imaging and transcriptomics to identify abnormalities in embryo structure and development. All data will be made freely available, enabling individual researchers to identify lines relevant to their research. The DMDD programme will coordinate its work with similar international efforts through the umbrella of the International Mouse Phenotyping Consortium [see accompanying Special Article (Adams et al., 2013] and, together, these programmes will provide a novel database for embryonic development, linking gene identity with molecular profiles and morphology phenotypes.

Study on investigation and evaluation methods of deep seated sedimentary rocks. Chemical weathering, pore water squeezing and relationships of physical properties of sedimentary rocks

International Nuclear Information System (INIS)

Oyama, Takahiro; Suzuki, Koichi

2006-01-01

Chemical weathering, porewater squeezing and physical properties for the sedimentary rocks were examined. Chemical weathering potential of rocks was described by the sulfur as a acceleration factor of weathering and carbonate contents as a neutralization factor of it. The carbonate contents in the rocks were measured accurately by the gas pressure measurement method. Pore water squeezing method was applied for the semi-hard sedimentary rocks (Opalinusclay). The chemical change of extracted pore water under high pressure conditions was estimated. Physical property of sedimentary rocks have relationship among the porosity and permeability and resistivity coefficient in the same rock types. It is possible to estimate the water permeability from the geophysical tests. (author)

Radiation injuries of plasmatic membrane and lethal action of radiation on cells

Energy Technology Data Exchange (ETDEWEB)

Fomenko, B S; Akoev, I G [AN SSSR, Pushchino-na-Oke. Inst. Biologicheskoj Fiziki

1984-01-01

Data on modification of procaryotes and eukaryotes cell injuries using preparations not penetrating into cells and also membrane-specific drugs localized in cells in a lipid phase are generalized. A conclusion is drawn that radiation injuries of plasmatic membrane of prokaryotes and eukaryotes contribute considerably to lethal action of radiation on cells.

Radiation injuries of plasmatic membrane and lethal action of radiation on cells

International Nuclear Information System (INIS)

Fomenko, B.S.; Akoev, I.G.

1984-01-01

Data on modification of procaryotes and eukaryotes cell injuries using preparations not penetrating into cells and also membrane-specific drugs localized in cells in a lipid phase are generalized. A conclusion is drawn that radiation injuries of plasmatic membrane of prokaryotes and eukaryotes contribute considerably to lethal action of radiation on cells

USP22 regulates oncogenic signaling pathways to drive lethal cancer progression.

Science.gov (United States)

Schrecengost, Randy S; Dean, Jeffry L; Goodwin, Jonathan F; Schiewer, Matthew J; Urban, Mark W; Stanek, Timothy J; Sussman, Robyn T; Hicks, Jessica L; Birbe, Ruth C; Draganova-Tacheva, Rossitza A; Visakorpi, Tapio; DeMarzo, Angelo M; McMahon, Steven B; Knudsen, Karen E

2014-01-01

Increasing evidence links deregulation of the ubiquitin-specific proteases 22 (USP22) deubitiquitylase to cancer development and progression in a select group of tumor types, but its specificity and underlying mechanisms of action are not well defined. Here we show that USP22 is a critical promoter of lethal tumor phenotypes that acts by modulating nuclear receptor and oncogenic signaling. In multiple xenograft models of human cancer, modeling of tumor-associated USP22 deregulation demonstrated that USP22 controls androgen receptor accumulation and signaling, and that it enhances expression of critical target genes coregulated by androgen receptor and MYC. USP22 not only reprogrammed androgen receptor function, but was sufficient to induce the transition to therapeutic resistance. Notably, in vivo depletion experiments revealed that USP22 is critical to maintain phenotypes associated with end-stage disease. This was a significant finding given clinical evidence that USP22 is highly deregulated in tumors, which have achieved therapeutic resistance. Taken together, our findings define USP22 as a critical effector of tumor progression, which drives lethal phenotypes, rationalizing this enzyme as an appealing therapeutic target to treat advanced disease.

Sub-lethal effects of pesticide residues in brood comb on worker honey bee (Apis mellifera development and longevity.

Directory of Open Access Journals (Sweden)

Judy Y Wu

Full Text Available BACKGROUND: Numerous surveys reveal high levels of pesticide residue contamination in honey bee comb. We conducted studies to examine possible direct and indirect effects of pesticide exposure from contaminated brood comb on developing worker bees and adult worker lifespan. METHODOLOGY/PRINCIPAL FINDINGS: Worker bees were reared in brood comb containing high levels of known pesticide residues (treatment or in relatively uncontaminated brood comb (control. Delayed development was observed in bees reared in treatment combs containing high levels of pesticides particularly in the early stages (day 4 and 8 of worker bee development. Adult longevity was reduced by 4 days in bees exposed to pesticide residues in contaminated brood comb during development. Pesticide residue migration from comb containing high pesticide residues caused contamination of control comb after multiple brood cycles and provided insight on how quickly residues move through wax. Higher brood mortality and delayed adult emergence occurred after multiple brood cycles in contaminated control combs. In contrast, survivability increased in bees reared in treatment comb after multiple brood cycles when pesticide residues had been reduced in treatment combs due to residue migration into uncontaminated control combs, supporting comb replacement efforts. Chemical analysis after the experiment confirmed the migration of pesticide residues from treatment combs into previously uncontaminated control comb. CONCLUSIONS/SIGNIFICANCE: This study is the first to demonstrate sub-lethal effects on worker honey bees from pesticide residue exposure from contaminated brood comb. Sub-lethal effects, including delayed larval development and adult emergence or shortened adult longevity, can have indirect effects on the colony such as premature shifts in hive roles and foraging activity. In addition, longer development time for bees may provide a reproductive advantage for parasitic Varroa destructor

B cells are not essential for Lactobacillus-mediated protection against lethal pneumovirus infection*

Science.gov (United States)

Percopo, Caroline M.; Dyer, Kimberly D.; Garcia-Crespo, Katia E.; Gabryszewski, Stanislaw J.; Shaffer, Arthur L.; Domachowske, Joseph B.; Rosenberg, Helene F.

2014-01-01

We have shown previously that priming of respiratory mucosa with live Lactobacillus species promotes robust and prolonged survival from an otherwise lethal infection with pneumonia virus of mice (PVM), a property known as heterologous immunity. Lactobacillus-priming results in a moderate reduction in virus recovery and a dramatic reduction in virus-induced proinflammatory cytokine production; the precise mechanisms underlying these findings remain to be elucidated. As B cells have been shown to promote heterologous immunity against respiratory virus pathogens under similar conditions, here we explore the role of B cells in Lactobacillus-mediated protection against acute pneumovirus infection. We found that Lactobacillus-primed mice feature elevated levels of airway immunoglobulins IgG, IgA and IgM and lung tissues with dense, B cell (B220+) enriched peribronchial and perivascular infiltrates with germinal centers consistent with descriptions of bronchus-associated lymphoid tissue. No B cells were detected in lung tissue of Lactobacillus-primed B-cell deficient μMT mice or Jh mice, and Lactobacillus-primed μMT mice had no characteristic infiltrates or airway immunoglobulins. Nonetheless, we observed diminished virus recovery and profound suppression of virus-induced proinflammatory cytokines CCL2, IFN-gamma, and CXCL10 in both wild-type and Lactobacillus-primed μMT mice. Furthermore, L. plantarum-primed, B-cell deficient μMT and Jh mice were fully protected from an otherwise lethal PVM infection, as were their respective wild-types. We conclude that B cells are dispensable for Lactobacillus-mediated heterologous immunity and were not crucial for promoting survival in response to an otherwise lethal pneumovirus infection. PMID:24748495

Immunobiotic Lactobacillus administered post-exposure averts the lethal sequelae of respiratory virus infection.

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Percopo, Caroline M; Rice, Tyler A; Brenner, Todd A; Dyer, Kimberly D; Luo, Janice L; Kanakabandi, Kishore; Sturdevant, Daniel E; Porcella, Stephen F; Domachowske, Joseph B; Keicher, Jesse D; Rosenberg, Helene F

2015-09-01

We reported previously that priming of the respiratory tract with immunobiotic Lactobacillus prior to virus challenge protects mice against subsequent lethal infection with pneumonia virus of mice (PVM). We present here the results of gene microarray which document differential expression of proinflammatory mediators in response to PVM infection alone and those suppressed in response to Lactobacillus plantarum. We also demonstrate for the first time that intranasal inoculation with live or heat-inactivated L. plantarum or Lactobacillus reuteri promotes full survival from PVM infection when administered within 24h after virus challenge. Survival in response to L. plantarum administered after virus challenge is associated with suppression of proinflammatory cytokines, limited virus recovery, and diminished neutrophil recruitment to lung tissue and airways. Utilizing this post-virus challenge protocol, we found that protective responses elicited by L. plantarum at the respiratory tract were distinct from those at the gastrointestinal mucosa, as mice devoid of the anti-inflammatory cytokine, interleukin (IL)-10, exhibit survival and inflammatory responses that are indistinguishable from those of their wild-type counterparts. Finally, although L. plantarum interacts specifically with pattern recognition receptors TLR2 and NOD2, the respective gene-deleted mice were fully protected against lethal PVM infection by L. plantarum, as are mice devoid of type I interferon receptors. Taken together, L. plantarum is a versatile and flexible agent that is capable of averting the lethal sequelae of severe respiratory infection both prior to and post-virus challenge via complex and potentially redundant mechanisms. Published by Elsevier B.V.

B cells are not essential for Lactobacillus-mediated protection against lethal pneumovirus infection.

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Percopo, Caroline M; Dyer, Kimberly D; Garcia-Crespo, Katia E; Gabryszewski, Stanislaw J; Shaffer, Arthur L; Domachowske, Joseph B; Rosenberg, Helene F

2014-06-01

We have shown previously that priming of respiratory mucosa with live Lactobacillus species promotes robust and prolonged survival from an otherwise lethal infection with pneumonia virus of mice, a property known as heterologous immunity. Lactobacillus priming results in a moderate reduction in virus recovery and a dramatic reduction in virus-induced proinflammatory cytokine production; the precise mechanisms underlying these findings remain to be elucidated. Because B cells have been shown to promote heterologous immunity against respiratory virus pathogens under similar conditions, in this study we explore the role of B cells in Lactobacillus-mediated protection against acute pneumovirus infection. We found that Lactobacillus-primed mice feature elevated levels of airway Igs IgG, IgA, and IgM and lung tissues with dense, B cell (B220(+))-enriched peribronchial and perivascular infiltrates with germinal centers consistent with descriptions of BALT. No B cells were detected in lung tissue of Lactobacillus-primed B cell deficient μMT mice or Jh mice, and Lactobacillus-primed μMT mice had no characteristic infiltrates or airway Igs. Nonetheless, we observed diminished virus recovery and profound suppression of virus-induced proinflammatory cytokines CCL2, IFN-γ, and CXCL10 in both wild-type and Lactobacillus-primed μMT mice. Furthermore, Lactobacillus plantarum-primed, B cell-deficient μMT and Jh mice were fully protected from an otherwise lethal pneumonia virus of mice infection, as were their respective wild-types. We conclude that B cells are dispensable for Lactobacillus-mediated heterologous immunity and were not crucial for promoting survival in response to an otherwise lethal pneumovirus infection.

[Underlying Mechanisms of Methamphetamine-Induced Self-Injurious Behavior and Lethal Effects in Mice].

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Mori, Tomohisa; Sawaguchi, Toshiko

2018-01-01

Relatively high doses of psychostimulants induce neurotoxicity on the dopaminergic system and self-injurious behavior (SIB) in rodents. However the underlying neuronal mechanisms of SIB remains unclear. Dopamine receptor antagonists, N-methyl-D-aspartic acid (NMDA) receptor antagonists, Nitric Oxide Synthase (NOS) inhibitors and free radical scavengers significantly attenuate methamphetamine-induced SIB. These findings indicate that activation of dopamine as well as NMDA receptors followed by radical formation and oxidative stress, especially when mediated by NOS activation, is associated with methamphetamine-induced SIB. On the other hand, an increase in the incidence of polydrug abuse is a major problem worldwide. Coadministered methamphetamine and morphine induced lethality in more than 80% in mice, accompanied by an increase in the number of poly (ADP-ribose) polymerase (PARP)-immunoreactive cells in the heart, kidney and liver. The lethal effect and the increase in the incidence of rupture or PARP-immunoreactive cells induced by the coadministration of methamphetamine and morphine were significantly attenuated by pretreatment with a phospholipase A2 inhibitor or a radical scavenger, or by cooling of body from 30 to 90 min after drug administration. These results suggest that free radicals play an important role in the increased lethality induced by the coadministration of methamphetamine and morphine. Therefore, free radical scavengers and cooling are beneficial for preventing death that is induced by the coadministration of methamphetamine and morphine. These findings may help us better understand for masochistic behavior, which is a clinical phenomenon on SIB, as well as polydrug-abuse-induced acute toxicity.

Lethal and sublethal effects of glyphosate (roundup active) to embryos of colombian anurans

International Nuclear Information System (INIS)

Triana Velasquez, Teofila Maria; Montes Rojas, Claudia; Bernal Bautista, Manuel Hernando

2013-01-01

Glyphosate is an herbicide widely used in agriculture, which may affect non-target species. the aim of this study was to determine the lethal (median lethal concentration - LC 5 0) and sublethal effects (changes on body size and development) of glyphosate (roundup active) to embryos of four anuran species, exposed during 96 hours under laboratory and microcosm tests. under laboratory conditions, engystomops pustulosus was the most tolerant species (LC 5 0 = 3033,18 ?g a.e./L) and rhinella marina was the most sensitive (lc50 = 1421,46 ?g a.e./L), which also showed a delayed development and significantly reduced body size. The other species had an intermediate LC50 (Rhinella humboldti = 2899.54 ?g a.e./L; hypsiboas crepitans = 2151,88 ?g a.e./L). In all cases, the laboratory LC 5 0 was lower than the concentration used in field (5392.92 ?g a.e./L), indicating a high toxic effect. In the microcosm tests, embryos of e. pustulosus were the most tolerant (LC 5 0 = 19,41 kg a.e./ha), while R. humboldti were the most sensitive (LC 5 0 = 10,61 kg a.e./ha). In this case, all four study species had a higher LC 5 0 than the concentration sprayed in field (3,69 kg a.e./ ha), so a lower lethal effect, and there were no significant differences in body size and development. This result shows that the glyphosate, as the commercial presentation roundup active, produce a moderate mortality on anuran embryos.

A hepatic protein, fetuin-A, occupies a protective role in lethal systemic inflammation.

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Wei Li

2011-02-01

Full Text Available A liver-derived protein, fetuin-A, was first purified from calf fetal serum in 1944, but its potential role in lethal systemic inflammation was previously unknown. This study aims to delineate the molecular mechanisms underlying the regulation of hepatic fetuin-A expression during lethal systemic inflammation (LSI, and investigated whether alterations of fetuin-A levels affect animal survival, and influence systemic accumulation of a late mediator, HMGB1.LSI was induced by endotoxemia or cecal ligation and puncture (CLP in fetuin-A knock-out or wild-type mice, and animal survival rates were compared. Murine peritoneal macrophages were challenged with exogenous (endotoxin or endogenous (IFN-γ stimuli in the absence or presence of fetuin-A, and HMGB1 expression and release was assessed. Circulating fetuin-A levels were decreased in a time-dependent manner, starting between 26 h, reaching a nadir around 24-48 h, and returning towards base-line approximately 72 h post onset of endotoxemia or sepsis. These dynamic changes were mirrored by an early cytokine IFN-γ-mediated inhibition (up to 50-70% of hepatic fetuin-A expression. Disruption of fetuin-A expression rendered animals more susceptible to LSI, whereas supplementation of fetuin-A (20-100 mg/kg dose-dependently increased animal survival rates. The protection was associated with a significant reduction in systemic HMGB1 accumulation in vivo, and parallel inhibition of IFN-γ- or LPS-induced HMGB1 release in vitro.These experimental data suggest that fetuin-A is protective against lethal systemic inflammation partly by inhibiting active HMGB1 release.

An alternative approach to risk rank chemicals on the threat they pose to the aquatic environment.

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Johnson, Andrew C; Donnachie, Rachel L; Sumpter, John P; Jürgens, Monika D; Moeckel, Claudia; Pereira, M Gloria

2017-12-01

This work presents a new and unbiased method of risk ranking chemicals based on the threat they pose to the aquatic environment. The study ranked 12 metals, 23 pesticides, 11 other persistent organic pollutants (POPs), 13 pharmaceuticals, 10 surfactants and similar compounds and 2 nanoparticles (total of 71) of concern against one another by comparing their median UK river water and median ecotoxicity effect concentrations. To complement this, by giving an assessment on potential wildlife impacts, risk ranking was also carried out by comparing the lowest 10th percentile of the effects data with the highest 90th percentile of the exposure data. In other words, risk was pared down to just toxicity versus exposure. Further modifications included incorporating bioconcentration factors, using only recent water measurements and excluding either lethal or sub-lethal effects. The top ten chemicals, based on the medians, which emerged as having the highest risk to organisms in UK surface waters using all the ecotoxicity data were copper, aluminium, zinc, ethinylestradiol (EE2), linear alkylbenzene sulfonate (LAS), triclosan, manganese, iron, methomyl and chlorpyrifos. By way of contrast, using current UK environmental quality standards as the comparator to median UK river water concentrations would have selected 6 different chemicals in the top ten. This approach revealed big differences in relative risk; for example, zinc presented a million times greater risk then metoprolol and LAS 550 times greater risk than nanosilver. With the exception of EE2, most pharmaceuticals were ranked as having a relatively low risk. Copyright © 2017 Elsevier B.V. All rights reserved.

Protection of melanized Cryptococcus neoformans from lethal dose gamma irradiation involves changes in melanin's chemical structure and paramagnetism.

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Abdelahad Khajo

Full Text Available Certain fungi thrive in highly radioactive environments including the defunct Chernobyl nuclear reactor. Cryptococcus neoformans (C. neoformans, which uses L-3,4-dihydroxyphenylalanine (L-DOPA to produce melanin, was used here to investigate how gamma radiation under aqueous aerobic conditions affects the properties of melanin, with the aim of gaining insight into its radioprotective role. Exposure of melanized fungal cell in aqueous suspensions to doses of γ-radiation capable of killing 50 to 80% of the cells did not lead to a detectable loss of melanin integrity according to EPR spectra of melanin radicals. Moreover, upon UV-visible (Xe-lamp illumination of melanized cells, the increase in radical population was unchanged after γ-irradiation. Gamma-irradiation of frozen cell suspensions and storage of samples for several days at 77 K however, produced melanin modification noted by a reduced radical population and reduced photoresponse. More direct evidence for structural modification of melanin came from the detection of soluble products with absorbance maxima near 260 nm in supernatants collected after γ-irradiation of cells and cell-free melanin. These products, which include thiobarbituric acid (TBA-reactive aldehydes, were also generated by Fenton reagent treatment of cells and cell-free melanin. In an assay of melanin integrity based on the metal (Bi(+3 binding capacity of cells, no detectable loss in binding was detected after γ-irradiation. Our results show that melanin in C. neoformans cells is susceptible to some damage by hydroxyl radical formed in lethal radioactive aqueous environments and serves a protective role in melanized fungi that involves sacrificial breakdown.

Mutagenic Potential of Nitroguanidine in the Drosophila melanogaster Sex-Linked Recessive Lethal Test

Science.gov (United States)

1988-07-01

Security Classification) Mtutagenic potential of nitroguan idine in the Drosophila melano- gaster sex-linked recessive lethal test 12. PERSONAL AUTHOR(S...Frederick, MD 21701-5012 Commander Commandant US Army Environmental Hygine Academy of Health Sciences. US Army Agency ATTN: AHS-CDM ATTN: Librarian, HSDH

{sup 1}H NMR metabolomics of earthworm exposure to sub-lethal concentrations of phenanthrene in soil

Energy Technology Data Exchange (ETDEWEB)

Brown, Sarah A.E.; McKelvie, Jennifer R.; Simpson, Andre J. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, Ontario, M1C 1A4 (Canada); Simpson, Myrna J., E-mail: myrna.simpson@utoronto.c [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, Ontario, M1C 1A4 (Canada)

2010-06-15

{sup 1}H NMR metabolomics was used to monitor earthworm responses to sub-lethal (50-1500 mg/kg) phenanthrene exposure in soil. Total phenanthrene was analyzed via soxhlet extraction, bioavailable phenanthrene was estimated by hydroxypropyl-beta-cyclodextrin (HPCD) and 1-butanol extractions and sorption to soil was assessed by batch equilibration. Bioavailable phenanthrene (HPCD-extracted) comprised approx65-97% of total phenanthrene added to the soil. Principal component analysis (PCA) showed differences in responses between exposed earthworms and controls after 48 h exposure. The metabolites that varied with exposure included amino acids (isoleucine, alanine and glutamine) and maltose. PLS models indicated that earthworm response is positively correlated to both total phenanthrene concentration and bioavailable (HPCD-extracted) phenanthrene in a freshly spiked, unaged soil. These results show that metabolomics is a powerful, direct technique that may be used to monitor contaminant bioavailability and toxicity of sub-lethal concentrations of contaminants in the environment. These initial findings warrant further metabolomic studies with aged contaminated soils. - {sup 1}H NMR metabolomics is used to directly monitor metabolic responses of Eisenia fetida after 48 h of exposure to sub-lethal concentrations of phenanthrene in soil.

Todralazine protects zebra fish from lethal doses of ionizing radiation: role of hematopoietic stem cell expansion

International Nuclear Information System (INIS)

Dimri, Manali; Joshi, Jaidev; Indracanti, Prem Kumar

2013-01-01

Radiation induced cell killing and hematopoietic stem cell depletion leads to compromised immune functions and opportunistic infections which significantly affect the recovery and survival upon irradiation. Any agent which can expand residual hematopoietic stem cells in irradiated organism can render protection from the effects of lethal doses of ionizing radiation. Johns Hopkins Clinical compound library (JHCCL) was screened for protection against lethal doses of ionizing radiation using developing zebra fish as a model organism. Modulation of radiation induced reactive oxygen species by the small molecules were done by DCFDA staining and for visual identification and quantification of apoptosis acridine orange assay, flow cytometry were employed respectively. Hematopoietic stem cell expansion potential was assessed by quantifying runx1 expression, a marker for definitive stem cells, were done by RT-PCR and by the kinetics of recovery from chemically induced anaemia. Todralazine hydrochloride from JHCCL exhibited promising results with potential anti radiation effects. A dose of 5μM was found to be the most effective and has rendered significant organ and whole body protection (100% survival advantage over a period of 6 days) against 20 Gy. However todralazine did not modulated radiation induced free radicals (monitored within 2 h of irradiation) and apoptosis in zebra fish embryos analysed at 8 and 24h post irradiation. Flow cytometric quantification of pre G1 population suggested the same. Chemoinformatics approaches were further carried out to elucidate possible targets which are contributing to its radioprotection potential. Structural similarity search suggested several targets and possible hematopoietic stem cell expanding potential. Treatment of zebra fish embryos with todralazine has lead to significant proliferation of hematopoietic stem cell as indicated by increase in expression of runx1. HSC expanding potential of todralazine was further supported by

Prion protein protects mice from lethal infection with influenza A viruses.

Directory of Open Access Journals (Sweden)

Junji Chida

2018-05-01

Full Text Available The cellular prion protein, designated PrPC, is a membrane glycoprotein expressed abundantly in brains and to a lesser extent in other tissues. Conformational conversion of PrPC into the amyloidogenic isoform is a key pathogenic event in prion diseases. However, the physiological functions of PrPC remain largely unknown, particularly in non-neuronal tissues. Here, we show that PrPC is expressed in lung epithelial cells, including alveolar type 1 and 2 cells and bronchiolar Clara cells. Compared with wild-type (WT mice, PrPC-null mice (Prnp0/0 were highly susceptible to influenza A viruses (IAVs, with higher mortality. Infected Prnp0/0 lungs were severely injured, with higher inflammation and higher apoptosis of epithelial cells, and contained higher reactive oxygen species (ROS than control WT lungs. Treatment with a ROS scavenger or an inhibitor of xanthine oxidase (XO, a major ROS-generating enzyme in IAV-infected lungs, rescued Prnp0/0 mice from the lethal infection with IAV. Moreover, Prnp0/0 mice transgenic for PrP with a deletion of the Cu-binding octapeptide repeat (OR region, Tg(PrPΔOR/Prnp0/0 mice, were also highly susceptible to IAV infection. These results indicate that PrPC has a protective role against lethal infection with IAVs through the Cu-binding OR region by reducing ROS in infected lungs. Cu content and the activity of anti-oxidant enzyme Cu/Zn-dependent superoxide dismutase, SOD1, were lower in Prnp0/0 and Tg(PrPΔOR/Prnp0/0 lungs than in WT lungs. It is thus conceivable that PrPC functions to maintain Cu content and regulate SOD1 through the OR region in lungs, thereby reducing ROS in IAV-infected lungs and eventually protecting them from lethal infection with IAVs. Our current results highlight the role of PrPC in protection against IAV infection, and suggest that PrPC might be a novel target molecule for anti-influenza therapeutics.

Patterning and gastrulation defects caused by the tw18 lethal are due to loss of Ppp2r1a

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Lisette Lange

2017-06-01

Full Text Available The mouse t haplotype, a variant 20 cM genomic region on Chromosome 17, harbors 16 embryonic control genes identified by recessive lethal mutations isolated from wild mouse populations. Due to technical constraints so far only one of these, the tw5 lethal, has been cloned and molecularly characterized. Here we report the molecular isolation of the tw18 lethal. Embryos carrying the tw18 lethal die from major gastrulation defects commencing with primitive streak formation at E6.5. We have used transcriptome and marker gene analyses to describe the molecular etiology of the tw18 phenotype. We show that both WNT and Nodal signal transduction are impaired in the mutant epiblast, causing embryonic patterning defects and failure of primitive streak and mesoderm formation. By using a candidate gene approach, gene knockout by homologous recombination and genetic rescue, we have identified the gene causing the tw18 phenotype as Ppp2r1a, encoding the PP2A scaffolding subunit PR65alpha. Our work highlights the importance of phosphatase 2A in embryonic patterning, primitive streak formation, gastrulation, and mesoderm formation downstream of WNT and Nodal signaling.

Lethal drugs in capital punishment in USA: History, present, and future perspectives.

Science.gov (United States)

Kas, Kristen; Yim, Richard; Traore, Salematou; ElFadaly, Marwa; Lang, Lynn; Freeman, Robert A; Parmar, Jayesh R; Kharel, Madan K

Lethal injection is the preferred method for the execution of condemned prisoners in the United States. A recent decision of The European Union to prohibit the export of drugs used in capital punishment to the USA along with domestic firms ceasing to manufacture these drugs has resulted in a drug shortage and a search for alternative drugs and new drug combinations that have not been previously validated for inducing death. As a consequence, some of the executions did not proceed as expected and sparked public debate regarding whether recent executions by lethal injection serve the purpose of avoiding "cruel and unusual punishment" in executions. Moreover, a cottage industry comprised of compounding pharmacies as emerged as a source of drug combinations used in capital punishment. Although there is a growing trend toward the abolishment of capital punishment in United States, the controversy concerning the efficacy of drug and involvement of health care professionals in the execution procedure is far from over. Copyright © 2015 Elsevier Inc. All rights reserved.

Lethal trap trees: a potential option for emerald ash borer (Agrilus planipennis Fairmaire) management.

Science.gov (United States)

McCullough, Deborah G; Poland, Therese M; Lewis, Phillip A

2016-05-01

Economic and ecological impacts of ash (Fraxinus spp.) mortality resulting from emerald ash borer (EAB) (Agrilus planipennis Fairmaire) invasion are severe in forested, residential and urban areas. Management options include girdling ash trees to attract ovipositing adult beetles and then destroying infested trees before larvae develop or protecting ash with a highly effective, systemic emamectin benzoate insecticide. Injecting this insecticide and then girdling injected trees a few weeks later could effectively create lethal trap trees, similar to a bait-and-kill tactic, if girdling does not interfere with insecticide translocation. We compared EAB larval densities on girdled trees, trees injected with the emamectin benzoate insecticide, trees injected with the insecticide and then girdled 18-21 days later and untreated controls at multiple sites. Pretreatment larval densities did not differ among treatments. Current-year larval densities were higher on girdled and control trees than on any trees treated with insecticide at all sites. Foliar residue analysis and adult EAB bioassays showed that girdling trees after insecticide injections did not reduce insecticide translocation. Girdling ash trees to attract adult EAB did not reduce efficacy of emamectin benzoate trunk injections applied ≥ 18 days earlier and could potentially be used in integrated management programs to slow EAB population growth. © 2015 Society of Chemical Industry.

Noise and neurotoxic chemical exposure relationship to workplace traumatic injuries: A review.

Science.gov (United States)

Estill, Cheryl Fairfield; Rice, Carol H; Morata, Thais; Bhattacharya, Amit

2017-02-01

More than 5,000 fatalities and eight million injuries occurred in the workplace in 2007 at a cost of $6 billion and $186 billion, respectively. Neurotoxic chemicals are known to affect central nervous system functions among workers, which include balance and hearing disorders. However, it is not known if there is an association between exposure to noise and solvents and acute injuries. A thorough review was conducted of the literature on the relationship between noise or solvent exposures and hearing loss with various health outcomes. The search resulted in 41 studies. Health outcomes included: hearing loss, workplace injuries, absence from work due to sickness, fatalities, hospital admissions due to workplace accidents, traffic accidents, hypertension, balance, slip, trips, or falls, cognitive measures, or disability retirement. Important covariates in these studies were age of employee, type of industry or occupation, or length of employment. Most authors that evaluated noise exposure concluded that higher exposure to noise resulted in more of the chosen health effect but the relationship is not well understood. Studies that evaluated hearing loss found that hearing loss was related to occupational injury, disability retirement, or traffic accidents. Studies that assessed both noise exposure and hearing loss as risk factors for occupational injuries reported that hearing loss was related to occupational injuries as much or more than noise exposure. Evidence suggests that solvent exposure is likely to be related to accidents or other health consequences such balance disorders. Many authors reported that noise exposures and hearing loss, respectively, are likely to be related to occupational accidents. Practical applications: The potential significance of the study is that findings could be used by managers to reduce injuries and the costs associated with those injures. Published by Elsevier Ltd.

Incompatibility between X chromosome factor and pericentric heterochromatic region causes lethality in hybrids between Drosophila melanogaster and its sibling species.

Science.gov (United States)

Cattani, M Victoria; Presgraves, Daven C

2012-06-01

The Dobzhansky-Muller model posits that postzygotic reproductive isolation results from the evolution of incompatible epistatic interactions between species: alleles that function in the genetic background of one species can cause sterility or lethality in the genetic background of another species. Progress in identifying and characterizing factors involved in postzygotic isolation in Drosophila has remained slow, mainly because Drosophila melanogaster, with all of its genetic tools, forms dead or sterile hybrids when crossed to its sister species, D. simulans, D. sechellia, and D. mauritiana. To circumvent this problem, we used chromosome deletions and duplications from D. melanogaster to map two hybrid incompatibility loci in F(1) hybrids with its sister species. We mapped a recessive factor to the pericentromeric heterochromatin of the X chromosome in D. simulans and D. mauritiana, which we call heterochromatin hybrid lethal (hhl), which causes lethality in F(1) hybrid females with D. melanogaster. As F(1) hybrid males hemizygous for a D. mauritiana (or D. simulans) X chromosome are viable, the lethality of deficiency hybrid females implies that a dominant incompatible partner locus exists on the D. melanogaster X. Using small segments of the D. melanogaster X chromosome duplicated onto the Y chromosome, we mapped a dominant factor that causes hybrid lethality to a small 24-gene region of the D. melanogaster X. We provide evidence suggesting that it interacts with hhl(mau). The location of hhl is consistent with the emerging theme that hybrid incompatibilities in Drosophila involve heterochromatic regions and factors that interact with the heterochromatin.

The role of non-protein sulphydryls in determining the chemical repair rates of free radical precursors of DNA damage and cell killing in Chinese hamster V79 cells

International Nuclear Information System (INIS)

Prise, K.M.; Davies, S.; Stratford, M.R.L.; Michael, B.D.

1992-01-01

Chinese hamster V79 fibroblasts were irradiated in the gas explosion apparatus and the chemical repair rates of the oxygen-dependent free radical precursors of DNA double-strand breaks (dsb) and lethal lesions measured using filter elution (pH 9.6) and a clonogenic assay. Depletion of cellular GSH levels, from 4.16 fmol/cell to 0.05 fmol/cell, by treatment with buthionine sulphoximine (50 μmol dm -3 ; 18 h), led to sensitization as regards DNA dsb induction and cell killing. This was evident at all time settings but was particularly pronounced when the oxygen shot was given 1 ms after the irradiation pulse. A detailed analysis of the chemical repair kinetics showed that depletion of GSH led to a reduction in the first-order rate constant for dsb precursors from 385 s -1 to 144 s -1 , and for lethal lesion precursors from 533 s -1 to 165 s -1 . (Author)

Protection of lethally irradiated mice with allogeneic fetal liver cells: influence of irradiation dose on immunologic reconstitution

International Nuclear Information System (INIS)

Tulunay, O.; Good, R.A.; Yunis, E.J.

1975-01-01

After lethal irradiation long-lived, immunologically vigorous C3Hf mice were produced by treatment with syngeneic fetal liver cells or syngeneic newborn or adult spleen cells. Treatment of lethally irradiated mice with syngeneic or allogeneic newborn thymus cells or allogeneic newborn or adult spleen cells regularly led to fatal secondary disease or graft-versus-host reactions. Treatment of the lethally irradiated mice with fetal liver cells regularly yielded long-lived, immunologically vigorous chimeras. The introduction of the fetal liver cells into the irradiated mice appeared to be followed by development of immunological tolerance of the donor cells. The findings suggest that T-cells at an early stage of differentiation are more susceptible to tolerance induction than are T-lymphocytes at later stages of differentiation. These investigations turned up a perplexing paradox which suggests that high doses of irradiation may injure the thymic stroma, rendering it less capable of supporting certain T-cell populations in the peripheral lymphoid tissue. Alternatively, the higher and not the lower dose of irradiation may have eliminated a host cell not readily derived from fetal liver precursors which represents an important helper cell in certain cell-mediated immune functions, e.g., graft-versus-host reactions, but which is not important in others, e.g., allograft rejections. The higher dose of lethal irradiation did not permit development or maintenance of a population of spleen cells that could initiate graft-versus-host reactions but did permit the development of a population of donor cells capable of achieving vigorous allograft rejection

Cell lethality after selective irradiation of the DNA replication fork

International Nuclear Information System (INIS)

Hofer, K.G.; Warters, R.L.

1985-01-01

It has been suggested that nascent DNA located at the DNA replication fork may exhibit enhanced sensitivity to radiation damage. To evaluate this hypothesis, Chinese hamster ovary cells (CHO) were labeled with 125 I-iododeoxyuridine ( 125 IUdR) either in the presence or absence of aphidicolin. Aphidicolin (5 μg/ml) reduced cellular 125 IUdR incorporation to 3-5% of the control value. The residual 125 I incorporation appeared to be restricted to low molecular weight (sub-replicon sized) fragments of DNA which were more sensitive to micrococcal nuclease attack and less sensitive to high salt DNase I digestion than randomly labeled DNA. These findings suggest that DNA replicated in the presence of aphidicolin remains localized at the replication fork adjacent to the nuclear matrix. Based on these observations an attempt was made to compare the lethal consequences of 125 I decays at the replication fork to that of 125 I decays randomly distributed over the entire genome. Regardless of the distribution of decay events, all treatment groups exhibited identical dose-response curves (D 0 : 101 125 I decays/cell). Since differential irradiation of the replication complex did not result in enhanced cell lethality, it can be concluded that neither the nascent DNA nor the protein components (replicative enzymes, nuclear protein matrix) associated with the DNA replication site constitute key radiosensitive targets within the cellular genome. (orig.)

Induction of dominant lethals in male mice treated as embryos with 35S

International Nuclear Information System (INIS)

Reddy, K.S.; Reddy, P.P.; Reddy, O.S.

1980-01-01

Pregnant female mice were injected (ip) with 20 μCi of 35 S or 0.5 ml of saline (control) on 3.5 day of gestation. The animals were allowed to litter and the (CBA female x C 3 H/He male) F 1 males treated as embryos were tested at maturity (8-10 weeks) for dominant lethal incidence. Each male was mated to 3 untreated virgin females for a period of 3 weeks. The pregnant animals were killed at mid gestation and the uterine contents and corpora lutea were examined. There was a significant increase in the frequency of dominant lethals both at pre- and post-implantation stages in the treated group when compared to controls. As a result a significant increase in dead implantations/female and reduction in live implantations/female were noticed in the treated group. Thus the results clearly delineate the genetic effects of sulfur-35 in mice. (auth.)

Oxygen-dependent radiosensitivity of Escherichia coli and mitigation in lethality by superoxide dismutase

International Nuclear Information System (INIS)

Niwa, Taeko; Yamaguchi, Hikoyuki; Yano, Keiji

1978-01-01

Oxygen-dependent radiosensitivity of Escherichia coli W3623 his - was confirmed. Regarding cellular superoxide dismutase (SOD), cells grown oxically gained higher activity than those anoxically, however, the reinforced enzyme level could not compensate the oxygen effect, i.e., the enhanced lethal effect of oxic γ-irradiation. Rather, the enhancement of oxygen effect was found in cells grown oxically compared with those anoxically. Oxygen enhanced lethality was mitigated to the extent by the amount of added SOD into the cell suspension to be irradiated. The results supported a proposal that superoxide anion, O 2 - , is involved in the oxygen effect, with the most likely site of the damage in the outer structure of cell but not in the cell matrix. Reverse oxygen effect could be found with lambda phage DNA in transfecting ability. Added SOD protected phage DNA somewhat in oxic irradiation. While considerable protections were found in anoxic one with the added SOD even autoclaved but their function was still unknown. (auth.)

Human cooperation by lethal group competition.

Science.gov (United States)

Egas, Martijn; Kats, Ralph; van der Sar, Xander; Reuben, Ernesto; Sabelis, Maurice W

2013-01-01

Why humans are prone to cooperate puzzles biologists, psychologists and economists alike. Between-group conflict has been hypothesized to drive within-group cooperation. However, such conflicts did not have lasting effects in laboratory experiments, because they were about luxury goods, not needed for survival ("looting"). Here, we find within-group cooperation to last when between-group conflict is implemented as "all-out war" (eliminating the weakest groups). Human subjects invested in helping group members to avoid having the lowest collective pay-off, whereas they failed to cooperate in control treatments with random group elimination or with no subdivision in groups. When the game was repeated, experience was found to promote helping. Thus, not within-group interactions alone, not random group elimination, but pay-off-dependent group elimination was found to drive within-group cooperation in our experiment. We suggest that some forms of human cooperation are maintained by multi-level selection: reciprocity within groups and lethal competition among groups acting together.

Experimental Salmonella typhimurium infections in rats. II. Active and passive immunization as protection against a lethal bacterial dose

DEFF Research Database (Denmark)

Hougen, H P; Jensen, E T; Klausen, B

1990-01-01

Immunization against a lethal dose of Salmonella typhimurium was studied in athymic and thymus-bearing LEW rats. Active immunization was performed with formalin-killed whole cell vaccine or sublethal infection prior to the lethal infection. After vaccination with killed bacteria the euthymic...... from immunized thymus grafted animals provided only limited protective effect, and treatment with cells from athymic animals had no effect. The study shows that although isogeneic thymus-grafted nude rats become resistent to reinfection with S. typhimurium, only large doses of spleen cells from...

Differential replication of foot-and-mouth disease viruses in mice determine lethality

Science.gov (United States)

Adult C57BL/6J mice have been used to study foot-and-mouth disease virus (FMDV) biology. In this work, two variants of an FMDV A/Arg/01 strain exhibiting differential pathogenicity in adult mice were identified and characterized: a non-lethal virus (A01NL) caused mild signs of disease, whereas a let...

Mutagenicity assayed by dominant lethality testing in mice fed a combined gamma-irradiated diet

International Nuclear Information System (INIS)

Rupova, I.; Katsarova, Ts.; Bajrakova, A.; Baev, I.; Tencheva, S.

1980-01-01

Mice fed a combined gamma-irradiated diet were examined for a mutagenic effect using the dominant lethality test. Their feed contained the following irradiated ingredients: 20% maize, 10% dried plums, and 5% walnut kernels. Taking into account cycle duration in spermatogenesis and oogenesis, males were fed this special diet throughout 56 days, and females throughout 21 days. The experiments involved three animal groups: (1) fed the special diet containing irradiated ingredients; (2) fed the special diet but with the ingredients nonirradiated; and (3) fed standard vivarium diet. Matings to provide the first generation were between one parent fed the special diet and a partner fed standard diet. With an adequate number of implants examined on day 16 of gestation, embryonic death rate was not found to be increased; hence, induction of dominant lethality from consumption of irradiated diet failed to be demonstrated

Additive vs non-additive genetic components in lethal cadmium tolerance of Gammarus (Crustacea): Novel light on the assessment of the potential for adaptation to contamination

International Nuclear Information System (INIS)

Chaumot, Arnaud; Gos, Pierre; Garric, Jeanne; Geffard, Olivier

2009-01-01

Questioning the likelihood that populations adapt to contamination is critical for ecotoxicological risk assessment. The appraisal of genetic variance in chemical sensitivities within populations is currently used to evaluate a priori this evolutionary potential. Nevertheless, conclusions from this approach are questionable since non-additive genetic components in chemical tolerance could limit the response of such complex phenotypic traits to selection. Coupling quantitative genetics with ecotoxicology, this study illustrates how the comparison between cadmium sensitivities among Gammarus siblings enabled discrimination between genetic variance components in chemical tolerance. The results revealed that, whereas genetically determined differences in lethal tolerance exist within the studied population, such differences were not significantly heritable since genetic variance mainly relied on non-additive components. Therefore the potential for genetic adaptation to acute Cd stress appeared to be weak. These outcomes are discussed in regard to previous findings for asexual daphnids, which suggest a strong potency of genetic adaptation to environmental contamination, but which contrast with compiled field observations where adaptation is not the rule. Hereafter, we formulate the reconciling hypothesis of a widespread weakness of additive components in tolerance to contaminants, which needs to be further tested to gain insight into the question of the likelihood of adaptation to contamination.

Anatase thin film with diverse epitaxial relationship grown on yttrium stabilized zirconia substrate by chemical vapor deposition

International Nuclear Information System (INIS)

Miyagi, Takahira; Ogawa, Tomoyuki; Kamei, Masayuki; Wada, Yoshiki; Mitsuhashi, Takefumi; Yamazaki, Atsushi

2003-01-01

An anatase epitaxial thin film with diverse epitaxial relationship, YSZ (001) // anatase (001), YSZ (010) // anatase (110), was grown on a single crystalline yttrium stabilized zirconia (YSZ) (001) substrate by metal organic chemical vapor deposition (MOCVD). The full width at half maximum (FWHM) of the (004) reflection of this anatase epitaxial film was 0.4deg, and the photoluminescence of this anatase epitaxial film showed visible emission with broad spectral width and large Stokes shift at room temperature. These results indicate that this anatase epitaxial film possessed almost equal crystalline quality compared with that grown under identical growth conditions on single crystalline SrTiO 3 substrate. (author)

Acute lethal toxicity following passive immunization for treatment of murine cryptococcosis.

OpenAIRE

Savoy, A C; Lupan, D M; Manalo, P B; Roberts, J S; Schlageter, A M; Weinhold, L C; Kozel, T R

1997-01-01

Passive immunization with monoclonal antibodies (MAbs) specific for the major capsular polysaccharide of Cryptococcus neoformans alters the course of murine cryptococcosis. During studies of passive immunization for treatment of murine cryptococcosis, we noted the occurrence of an acute, lethal toxicity. Toxicity was characterized by scratching, lethargy, respiratory distress, collapse, and death within 20 to 60 min after injection of antibody. The toxic effect was observed only in mice with ...

Perinatally lethal short rib-polydactyly syndromes. Pt. 1

International Nuclear Information System (INIS)

Sillence, D.; Kozlowski, K.; Bar-ziv, J.; Fuhrmann-Rieger, A.; Fuhrmann, W.; Pascu, F.

1987-01-01

Thirteen newborns with lethal short rib-polydactyly (SRP) have been reviewed, 11 with SRP type 3 (Verma-Naumoff) and 2 with SRP tye 2 (Majewski). In the former group there were three sets of siblings. The excess of males with SRP type III (Verma-Naumoff) is confirmed in this present study. A high frequency of phenotypic females including sex-reversed constitutional males with SRP type 1 (Saldino-Noonan) is in marked contrast to these findings in SRP type 3. Possible hypotheses include variable expressivity in non-Majewski short rib-polydactyly syndromes with sex-reversed and constitutional female cases tending to show more severe phenotypic expression both in terms of major anomalies and skeletal dysplastic effects. (orig.)

Disruption of the Sec24d gene results in early embryonic lethality in the mouse.

Directory of Open Access Journals (Sweden)

Andrea C Baines

Full Text Available Transport of newly synthesized proteins from the endoplasmic reticulum (ER to the Golgi is mediated by the coat protein complex COPII. The inner coat of COPII is assembled from heterodimers of SEC23 and SEC24. Though mice with mutations in one of the four Sec24 paralogs, Sec24b, exhibit a neural tube closure defect, deficiency in humans or mice has not yet been described for any of the other Sec24 paralogs. We now report characterization of mice with targeted disruption of Sec24d. Early embryonic lethality is observed in mice completely deficient in SEC24D, while a hypomorphic Sec24d allele permits survival to mid-embryogenesis. Mice haploinsufficient for Sec24d exhibit no phenotypic abnormality. A BAC transgene containing Sec24d rescues the embryonic lethality observed in Sec24d-null mice. These results demonstrate an absolute requirement for SEC24D expression in early mammalian development that is not compensated by the other three Sec24 paralogs. The early embryonic lethality resulting from loss of SEC24D in mice contrasts with the previously reported mild skeletal phenotype of SEC24D deficiency in zebrafish and restricted neural tube phenotype of SEC24B deficiency in mice. Taken together, these observations suggest that the multiple Sec24 paralogs have developed distinct functions over the course of vertebrate evolution.

Combined genetic effects of chemicals and radiation

International Nuclear Information System (INIS)

Kada, T.; Inoue, T.; Yokoiyama, A.; Russell, L.B.

1979-01-01

The interactions of chemicals and radiation are complex, and there may exist other unexpected patterns. The photodynamic induction of mutation by fluorescein dyes, and the radiosensitization with iodine compounds are classified as the interactions of chemicals and radiation outside cells. On the other hand, the antimutagenic effects of cobaltous chloride is concerned with the events taking place in the cells that had already been exposed to mutagenic agents. It is likely that the action of mutagenic agents is not direct, and that cellular functions, such as mutators or repair systems, are involved in the mutagenesis initiated by the agents. Such cellular functions can be affected by a second agent. In sexually reproducing organisms, two agents can also act on separate cells (male and female germ cells) which subsequently fuse. In mice, the experiments combining the radiation applied to one sex with the chemicals given to the other sex are only in early stages. Males were irradiated with X-ray (spermatozoa and spermatids sampled) and females (mature oocytes) were treated with caffeine. When the endpoint was dominant lethal, the level of X-ray effect induced in the male genome was independent of the caffeine treatment of the female. However, when the endpoint was sex-chromosome-loss, and a different strain of female was used, the caffeine potentiation was statistically significant at 5% level. (Yamashita, S.)

BRINE SHRIMP LETHALITY BIOASSAY OF GLAUCIUM GRANDIFLORUM VAR. GRANDIFLORUM

OpenAIRE

A. SARI, Ç. ÜNSAL, İ. SARIOĞLU, A. SARI, Ç. ÜNSAL, İ. SARIOĞLU

2013-01-01

Türkiye'nin 3 farklı bölgesinden toplanan Glaucium grandiflorum Boiss. et Huet var. grandiflorum örneklerinin toprak üstü kısımlarından elde edilen alkaloit ekstreleri ve bu ekstrelerden elde edilen majör alkaloitler allokriptopin, protopİn, (+)-izokoridin, (+)-korİdin üzerinde brİne shrimp lethality testi yapılarak sitotoksisiteleri İncelenmiştir. Glaucium grandiflorum var. grandiflorum türünün 3 örneği de önemli oranda sitotoksik aktİvite göstermiştir. Allokriptopin, protopin, (+)-izok...

An analysis of lethal and sublethal interactions among type I and type II pyrethroid pesticide mixtures using standard Hyalella azteca water column toxicity tests.

Science.gov (United States)

Hoffmann, Krista Callinan; Deanovic, Linda; Werner, Inge; Stillway, Marie; Fong, Stephanie; Teh, Swee

2016-10-01

A novel 2-tiered analytical approach was used to characterize and quantify interactions between type I and type II pyrethroids in Hyalella azteca using standardized water column toxicity tests. Bifenthrin, permethrin, cyfluthrin, and lambda-cyhalothrin were tested in all possible binary combinations across 6 experiments. All mixtures were analyzed for 4-d lethality, and 2 of the 6 mixtures (permethrin-bifenthrin and permethrin-cyfluthrin) were tested for subchronic 10-d lethality and sublethal effects on swimming motility and growth. Mixtures were initially analyzed for interactions using regression analyses, and subsequently compared with the additive models of concentration addition and independent action to further characterize mixture responses. Negative interactions (antagonistic) were significant in 2 of the 6 mixtures tested, including cyfluthrin-bifenthrin and cyfluthrin-permethrin, but only on the acute 4-d lethality endpoint. In both cases mixture responses fell between the additive models of concentration addition and independent action. All other mixtures were additive across 4-d lethality, and bifenthrin-permethrin and cyfluthrin-permethrin were also additive in terms of subchronic 10-d lethality and sublethal responses. Environ Toxicol Chem 2016;35:2542-2549. © 2016 SETAC. © 2016 SETAC.

A pharmacological screen for compounds that rescue the developmental lethality of a Drosophila ATM mutant.

Science.gov (United States)

Rimkus, Stacey A; Wassarman, David A

2018-01-01

Ataxia-telangiectasia (A-T) is a neurodegenerative disease caused by mutation of the A-T mutated (ATM) gene. ATM encodes a protein kinase that is activated by DNA damage and phosphorylates many proteins, including those involved in DNA repair, cell cycle control, and apoptosis. Characteristic biological and molecular functions of ATM observed in mammals are conserved in Drosophila melanogaster. As an example, conditional loss-of-function ATM alleles in flies cause progressive neurodegeneration through activation of the innate immune response. However, unlike in mammals, null alleles of ATM in flies cause lethality during development. With the goals of understanding biological and molecular roles of ATM in a whole animal and identifying candidate therapeutics for A-T, we performed a screen of 2400 compounds, including FDA-approved drugs, natural products, and bioactive compounds, for modifiers of the developmental lethality caused by a temperature-sensitive ATM allele (ATM8) that has reduced kinase activity at non-permissive temperatures. Ten compounds reproducibly suppressed the developmental lethality of ATM8 flies, including Ronnel, which is an organophosphate. Ronnel and other suppressor compounds are known to cause mitochondrial dysfunction or to inhibit the enzyme acetylcholinesterase, which controls the levels of the neurotransmitter acetylcholine, suggesting that detrimental consequences of reduced ATM kinase activity can be rescued by inhibiting the function of mitochondria or increasing acetylcholine levels. We carried out further studies of Ronnel because, unlike the other compounds that suppressed the developmental lethality of homozygous ATM8 flies, Ronnel was toxic to the development of heterozygous ATM8 flies. Ronnel did not affect the innate immune response of ATM8 flies, and it further increased the already high levels of DNA damage in brains of ATM8 flies, but its effects were not harmful to the lifespan of rescued ATM8 flies. These results provide

Highly variable penetrance of abnormal phenotypes in embryonic lethal knockout mice

Science.gov (United States)

Wilson, Robert; Geyer, Stefan H.; Reissig, Lukas; Rose, Julia; Szumska, Dorota; Hardman, Emily; Prin, Fabrice; McGuire, Christina; Ramirez-Solis, Ramiro; White, Jacqui; Galli, Antonella; Tudor, Catherine; Tuck, Elizabeth; Mazzeo, Cecilia Icoresi; Smith, James C.; Robertson, Elizabeth; Adams, David J.; Mohun, Timothy; Weninger, Wolfgang J.

2017-01-01

Background: Identifying genes that are essential for mouse embryonic development and survival through term is a powerful and unbiased way to discover possible genetic determinants of human developmental disorders. Characterising the changes in mouse embryos that result from ablation of lethal genes is a necessary first step towards uncovering their role in normal embryonic development and establishing any correlates amongst human congenital abnormalities. Methods: Here we present results gathered to date in the Deciphering the Mechanisms of Developmental Disorders (DMDD) programme, cataloguing the morphological defects identified from comprehensive imaging of 220 homozygous mutant and 114 wild type embryos from 42 lethal and subviable lines, analysed at E14.5. Results: Virtually all mutant embryos show multiple abnormal phenotypes and amongst the 42 lines these affect most organ systems. Within each mutant line, the phenotypes of individual embryos form distinct but overlapping sets. Subcutaneous edema, malformations of the heart or great vessels, abnormalities in forebrain morphology and the musculature of the eyes are all prevalent phenotypes, as is loss or abnormal size of the hypoglossal nerve. Conclusions: Overall, the most striking finding is that no matter how profound the malformation, each phenotype shows highly variable penetrance within a mutant line. These findings have challenging implications for efforts to identify human disease correlates. PMID:27996060

Caffeine protects mice against whole-body lethal dose of {gamma}-irradiation

Energy Technology Data Exchange (ETDEWEB)

George, K.C.; Hebbar, S.A.; Kale, S.P.; Kesavan, P.C. [Biosciences Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India)

1999-06-01

Administration of caffeine (1,3,7-trimethylxanthine), a major component of coffee, to Swiss mice at doses of 80 or 100 mg/kg body weight 60 min prior to whole-body lethal dose of {gamma}-irradiation (7.5 Gy) resulted in the survival of 70 and 63% of animals, respectively, at the above doses in contrast to absolutely no survivors (LD-100/25 days) in the group exposed to radiation alone. Pre-treatment with a lower concentration of caffeine (50 mg/kg) did not confer any radioprotection. The protection exerted by caffeine (80 mg/kg), however, was reduced from 70 to 50% if administered 30 min prior to irradiation. The trend statistics reveal that a dose of 80 mg/kg administered 60 min before whole-body exposure to 7.5 Gy is optimal for maximal radioprotection. However, caffeine (80 mg/kg) administered within 3 min after irradiation offered no protection. While there is documentation in the literature that caffeine is an antioxidant and radioprotector against the toxic pathway of radiation damage in a wide range of cells and organisms, this is the first report demonstrating unequivocally its potent radioprotective action in terms of survival of lethally whole-body irradiated mice. (author)

Human synthetic lethal inference as potential anti-cancer target gene detection

Directory of Open Access Journals (Sweden)

Solé Ricard V

2009-12-01

Full Text Available Abstract Background Two genes are called synthetic lethal (SL if mutation of either alone is not lethal, but mutation of both leads to death or a significant decrease in organism's fitness. The detection of SL gene pairs constitutes a promising alternative for anti-cancer therapy. As cancer cells exhibit a large number of mutations, the identification of these mutated genes' SL partners may provide specific anti-cancer drug candidates, with minor perturbations to the healthy cells. Since existent SL data is mainly restricted to yeast screenings, the road towards human SL candidates is limited to inference methods. Results In the present work, we use phylogenetic analysis and database manipulation (BioGRID for interactions, Ensembl and NCBI for homology, Gene Ontology for GO attributes in order to reconstruct the phylogenetically-inferred SL gene network for human. In addition, available data on cancer mutated genes (COSMIC and Cancer Gene Census databases as well as on existent approved drugs (DrugBank database supports our selection of cancer-therapy candidates. Conclusions Our work provides a complementary alternative to the current methods for drug discovering and gene target identification in anti-cancer research. Novel SL screening analysis and the use of highly curated databases would contribute to improve the results of this methodology.

Simulation and Validation of Cisco Lethal Conditions in Minnesota Lakes under Past and Future Climate Scenarios Using Constant Survival Limits

Directory of Open Access Journals (Sweden)

Liping Jiang

2016-07-01

Full Text Available Fish habitat in lakes is strongly constrained by water temperature (T and available dissolved oxygen (DO that are changed under climate warming. A one dimensional, dynamic water quality model MINLAKE2012 was used for T and DO simulation over 48 years. A fish habitat model FishHabitat2013 using simulated T and DO profiles as input was developed to determine lethal conditions of cisco Corgenous artedi in Minnesota lakes. Twenty-three lakes that had observations of cisco mortality or survival in the unusually warm summer of 2006 were used for model validation. The cisco habitat model used a lethal temperature of 22.1 °C and DO survival limit of 3 mg/L determined through model validation and sensitivity analysis. Cisco lethal conditions in 12 shallow, 16 medium-depth, and 30 deep virtual lakes were then simulated. Isopleths of total number of years with cisco kill and average cisco kill days for the years with kills under past (1961–2008 and future climate were generated to understand/extrapolate climate impacts on cisco in 620 Minnesota lakes. Shallow and medium-depth lakes are projected to not be good candidates for cisco refuge lakes, but deep lakes are possible cisco refuge lakes based on lethal condition projection under future warmer climate.

Identification and Prioritization of Relationships between Environmental Stressors and Adverse Human Health Impacts.

Science.gov (United States)

Bell, Shannon M; Edwards, Stephen W

2015-11-01

There are > 80,000 chemicals in commerce with few data available describing their impacts on human health. Biomonitoring surveys, such as the NHANES (National Health and Nutrition Examination Survey), offer one route to identifying possible relationships between environmental chemicals and health impacts, but sparse data and the complexity of traditional models make it difficult to leverage effectively. We describe a workflow to efficiently and comprehensively evaluate and prioritize chemical-health impact relationships from the NHANES biomonitoring survey studies. Using a frequent itemset mining (FIM) approach, we identified relationships between chemicals and health biomarkers and diseases. The FIM method identified 7,848 relationships between 219 chemicals and 93 health outcomes/biomarkers. Two case studies used to evaluate the FIM rankings demonstrate that the FIM approach is able to identify published relationships. Because the relationships are derived from the vast majority of the chemicals monitored by NHANES, the resulting list of associations is appropriate for evaluating results from targeted data mining or identifying novel candidate relationships for more detailed investigation. Because of the computational efficiency of the FIM method, all chemicals and health effects can be considered in a single analysis. The resulting list provides a comprehensive summary of the chemical/health co-occurrences from NHANES that are higher than expected by chance. This information enables ranking and prioritization on chemicals or health effects of interest for evaluation of published results and design of future studies. Bell SM, Edwards SW. 2015. Identification and prioritization of relationships between environmental stressors and adverse human health impacts. Environ Health Perspect 123:1193-1199; http://dx.doi.org/10.1289/ehp.1409138.

Estimation of the contribution of ionization and excitation to the lethal effect of ionizing radiation

International Nuclear Information System (INIS)

Petin, V.G.; Komarov, V.P.

1982-01-01

A simple theoretical model is proposed for estimating the differential contribution of ionization and excitation to the lethal effect of ionizing radiation. Numerical results were obtained on the basis of published experimental data on the ability of bacterial cells Escherichia coli to undergo photoreactivation of radiation-induced damage. It was shown that inactivation by excitation may be highly significant for UV-hypersensitive cells capable of photoreactivation; inactivation by excitation increased with the energy of ionizing radiation and the volume of irradiated suspensions. The data are in qualitative agreement with the assumption of a possible contribution of the UV-component of Cerenkov radiation to the formation of excitations responsible for the lethal effect and the phenomenon of photoreactivation after ionizing radiation. Some predictions from the model are discussed. (orig.)

Lethal subarachnoid bleeding under immunosuppressive therapy due to mycotic arteritis

International Nuclear Information System (INIS)

Weigel, S.; Kloska, S.; Freund, M.; Kehl, H.G.

2003-01-01

A subarachnoid haemorrhage (SAH) occurred 67 days after cardiac transplantation in 10-year-old girl with consecutive immunocompromising therapy. Neither digital subtraction angiography (DSA) nor computed tomographic angiography showed signs of intracranial vascular malformations. One month before the lethal SAH occurred, she had developed arterial hypertension and attacks of severe headache with cerebrospinal fluid (CSF) pleocytosis while CT scans showed an infarct of the left thalamus. Pathologic findings established the rare diagnosis of SAH due to aspergillosis-related mycotic arteritis. Imaging characteristics are presented. (orig.)

Detecting Chemical Weapons: Threats, Requirements, Solutions, and Future Challenges

Science.gov (United States)

Boso, Brian

2011-03-01

Although chemicals have been reportedly used as weapons for thousands of years, it was not until 1915 at Ypres, France that an industrial chemical, chlorine, was used in World War I as an offensive weapon in significant quantity, causing mass casualties. From that point until today the development, detection, production and protection from chemical weapons has be an organized endeavor of many of the world's armed forces and in more recent times, non-governmental terrorist organizations. The number of Chemical Warfare Agents (CWAs) has steadily increased as research into more toxic substances continued for most of the 20 th century. Today there are over 70 substances including harassing agents like tear gas, incapacitating agents, and lethal agents like blister, blood, chocking, and nerve agents. The requirements for detecting chemical weapons vary depending on the context in which they are encountered and the concept of operation of the organization deploying the detection equipment. The US DoD, for example, has as a requirement, that US forces be able to continue their mission, even in the event of a chemical attack. This places stringent requirements on detection equipment. It must be lightweight (developed for this application, including, but not limited to: mass spectroscopy, IR spectroscopy, RAMAN spectroscopy, MEMs micro-cantilever sensors, surface acoustic wave sensors, differential mobility spectrometry, and amplifying fluorescence polymers. In the future the requirements for detection equipment will continue to become even more stringent. The continuing increase in the sheer number of threats that will need to be detected, the development of binary agents requiring that even the precursor chemicals be detected, the development of new types of agents unlike any of the current chemistries, and the expansion of the list of toxic industrial chemical will require new techniques with higher specificity and more sensitivity.

PFOS, PFNA, and PFOA sub-lethal exposure to embryonic zebrafish have different toxicity profiles in terms of morphometrics, behavior and gene expression.

Science.gov (United States)

Jantzen, Carrie E; Annunziato, Kate A; Bugel, Sean M; Cooper, Keith R

2016-06-01

Polyfluorinated compounds (PFC) are a class of anthropogenic, persistent and toxic chemicals. PFCs are detected worldwide and consist of fluorinated carbon chains of varying length, terminal groups, and industrial uses. Previous zebrafish studies in the literature as well as our own studies have shown that exposure to these chemicals at a low range of concentrations (0.02-2.0μM; 20-2000ppb) resulted in chemical specific developmental defects and reduced post hatch survival. It was hypothesized that sub-lethal embryonic exposure to perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), or perfluorooctanoic acid (PFOA) would result in different responses with regard to morphometric, behavior, and gene expression in both yolk sac fry and larval zebrafish. Zebrafish were exposed to PFOS, PFOA, and PFNA (0.02, 0.2, 2.0μM) for the first five days post fertilization (dpf) and analyzed for morphometrics (5 dpf, 14 dpf), targeted gene expression (5 dpf, 14 dpf), and locomotive behavior (14 dpf). All three PFCs commonly resulted in a decrease in total body length, increased tfc3a (muscle development) expression and decreased ap1s (protein transport) expression at 5dpf, and hyperactive locomotor activity 14 dpf. All other endpoints measured at both life-stage time points varied between each of the PFCs. PFOS, PFNA, and PFOA exposure resulted in significantly altered responses in terms of morphometric, locomotion, and gene expression endpoints, which could be manifested in field exposed teleosts. Copyright © 2016 Elsevier B.V. All rights reserved.

Therapeutic use of recombinant human G-CSF (rhG-CSF) in a canine model of sublethal and lethal whole-body irradiation

International Nuclear Information System (INIS)

MacVittie, T.J.; Monroy, R.L.; Patchen, M.L.; Souza, L.M.

1990-01-01

Recombinant human G-CSF (rhG-CSF) was studied for its ability to modulate haemopoiesis in normal dogs as well as to decrease therapeutically the severity and duration of neutropenia in sublethally and lethally irradiated dogs. Data indicate that in the lethally irradiated dog, effective cytokine therapy with rhG-CSF will increase survival through the induction of earlier recovery of neutrophils and platelets. (author)

The (noneffects of lethal population control on the diet of Australian dingoes.

Directory of Open Access Journals (Sweden)

Benjamin L Allen

Full Text Available Top-predators contribute to ecosystem resilience, yet individuals or populations are often subject to lethal control to protect livestock, managed game or humans from predation. Such management actions sometimes attract concern that lethal control might affect top-predator function in ways ultimately detrimental to biodiversity conservation. The primary function of a predator is predation, which is often investigated by assessing their diet. We therefore use data on prey remains found in 4,298 Australian dingo scats systematically collected from three arid sites over a four year period to experimentally assess the effects of repeated broad-scale poison-baiting programs on dingo diet. Indices of dingo dietary diversity and similarity were either identical or near-identical in baited and adjacent unbaited treatment areas in each case, demonstrating no control-induced change to dingo diets. Associated studies on dingoes' movement behaviour and interactions with sympatric mesopredators were similarly unaffected by poison-baiting. These results indicate that mid-sized top-predators with flexible and generalist diets (such as dingoes may be resilient to ongoing and moderate levels of population control without substantial alteration of their diets and other related aspects of their ecological function.

Evaluation of the performance of three elastomers for non-lethal projectile applications

Science.gov (United States)

Thota, N.; Epaarachchi, J.; Lau, K. T.

2015-09-01

Less lethal kinetic ammunitions with soft noses such as eXact iMpact 1006, National Sports Spartan and B&T have been commonly used by military and law enforcement officers in the situations where lethal force is not warranted. In order to explore new materials to be used as nose in such ammunitions, a scholastic study using finite element simulations has been carried out to evaluate the effectiveness of two rubber like elastomers and a polyolefinic foam (low density, highly compressible, stiff and closed cell type of thermos plastic elastomer). State-of-the art thorax surrogate MTHOTA has been employed for the evaluation of blunt thoracic trauma. Force-rigid wall method was employed for the evaluation of head damage curves for each material. XM 1006 has been used as the benchmark projectile for the purpose of comparison. Both blunt thoracic trauma and head damage criterion point of view, both rubbers (R1 and R2) have yielded high values of VCmax and peak impact force. Polyolefinic foam (F1) considered in the study has yielded very promising VCmax values and very less peak impact force when compared with those of bench mark projectile XM 1006.

The Influence of criminal history on the likelihood of committing lethal versus nonlethal violence

NARCIS (Netherlands)

Ganpat, Soenita M.; Liem, Marieke; van der Leun, Joanne; Nieuwbeerta, Paul

2014-01-01

This study focuses on the criminal history of serious violent offenders. Our aim is to determine: (a) to what extent the criminal history of lethally violent offenders differs from nonlethally violent offenders and (b) to what extent one's criminal history influences the likelihood that violence

Lethal Nipah virus infection induces rapid overexpression of CXCL10.

Directory of Open Access Journals (Sweden)

Cyrille Mathieu

Full Text Available Nipah virus (NiV is a recently emerged zoonotic Paramyxovirus that causes regular outbreaks in East Asia with mortality rate exceeding 75%. Major cellular targets of NiV infection are endothelial cells and neurons. To better understand virus-host interaction, we analyzed the transcriptome profile of NiV infection in primary human umbilical vein endothelial cells. We further assessed some of the obtained results by in vitro and in vivo methods in a hamster model and in brain samples from NiV-infected patients. We found that NiV infection strongly induces genes involved in interferon response in endothelial cells. Among the top ten upregulated genes, we identified the chemokine CXCL10 (interferon-induced protein 10, IP-10, an important chemoattractant involved in the generation of inflammatory immune response and neurotoxicity. In NiV-infected hamsters, which develop pathology similar to what is seen in humans, expression of CXCL10 mRNA was induced in different organs with kinetics that followed NiV replication. Finally, we showed intense staining for CXCL10 in the brain of patients who succumbed to lethal NiV infection during the outbreak in Malaysia, confirming induction of this chemokine in fatal human infections. This study sheds new light on NiV pathogenesis, indicating the role of CXCL10 during the course of infection and suggests that this chemokine may serve as a potential new marker for lethal NiV encephalitis.

Oxygen and SO2 Consumption Rates in White and Rosé Wines: Relationship with and Effects on Wine Chemical Composition.

Science.gov (United States)

Carrascón, Vanesa; Bueno, Mónica; Fernandez-Zurbano, Purificación; Ferreira, Vicente

2017-11-01

This Article addresses the study of O 2 and SO 2 consumption rates of white and rosé wines, their relationship to the initial chemical composition, and their effects on the chemical changes experienced by wine during oxidation. Eight wines were subjected to five consecutive air-saturation cycles. O 2 was monitored periodically; SO 2 , color, and antioxidant indexes were determined after each cycle, and the initial and final compositions of the wines were thoroughly determined. Wines consumed oxygen at progressively decreasing rates. In the last cycles, after a strong decrease, consistent increases of oxygen levels were seen. Oxygen consumption rates were satisfactorily modeled, being proportional to wine copper, quercetin, and kaempherol contents and negatively proportional to cinnamic acids. SO 2 consumption rates were highly diverse between wines and were positively related to free SO 2 , Mn, and pH, among others. In the last saturations, SO 2 consumption took place regardless of O 2 consumption, implying that SO 2 should reduce chemical species oxidized in previous saturations. Some volatile phenols seem to be the end point of radical-mediated oxidation of polyphenols taking place preferably in the first saturation.

The lethal effect of longwave ultraviolet light and PUVA. An analysis based upon human mesenchymal cells in vitro

International Nuclear Information System (INIS)

Jongh, G. de; Bergers, M.; Boezeman, J.B.M.; Verhagen, A.R.; Mier, P.D.

1984-01-01

The lethal effect of UVA and PUVA radiation was studied in cultures of fresh and mature monocytes. UVA radiation alone was shown to possess a lethal effect at doses which are attained in the dermis in vivo. The synergistic action of 8-methoxypsoralen and UVA radiation predominated in PUVA radiation, but again a residual effect of UVA alone was demonstrated mathematically. Mature cells were less sensitive than fresh monocytes. The results indicate that a monolayer culture of non-dividing, mesenchymal cells offers considerable advantages over in vivo systems as a model for the study of phototoxicity. (author)

Intercellular distribution of mutations induced in oopcytes of Drosophila melanogaster by chemical and physical mutagens

International Nuclear Information System (INIS)

Traut, H.

1979-01-01

When females of Drosophila melanogaster are treated with chemical or physical mutagens, not only in one but also in both of the two homologous X chromosomes of a given oocyte, a recessive sex-linked lethal mutation may be induced. A method is described that discriminates between such single and double mutations. A theory is developed to show how a comparison betweeen the expected and the observer frequency of double mutations yields an indication of the intercellular distribution (random or nonrandom) of recessive lethal mutations induced by mutagenic agents in oocytes and, consequently, of the distribution (homogenous or nonhomogeneous) of those agents. Three agents were tested: FUdR (12.5, 50.0 and 81.0 μg/ml), mitomycin C (130.0 μg/ml) and x rays (2000 R, 150 kV). After FUdR feeding, no increase in the mutation frequency usually observed in D. melanogaster without mutagenic treatment was obtained (u = 0.13%, namely three single mutations among 2332 chromosomes tested). After mitomycin C feeding 104 single and three double mutations were obtained. All of the 50 mutations observed after x irradiation were single mutations. The results obtained in the mitomycin C and radiation experiments favor the assumption of a random intercellular distribution of recessive lethal mutations induced by these two agents in oocytes of D. melanogaster. Reasons are discussed why for other types of mutagenic agents nonrandom distributions may be observed with our technique

Lethal effects of solar radiation in proficient and deficient bacteria in repair systems

International Nuclear Information System (INIS)

Sousa Neto, A. de.

1980-01-01

A study of the lethal action of solar radiation on strains of E.coli K12, proficient or deficient in repair systems, as well as the wild type strain gene products are involved in repair of damage induced by solar radiation. The inactivation of the various bacterial strains (normalized to a dose equivalent to radiation at a wavelength 254 nm) suggests that the more energetic wavelengths of the solar spectrum (290-320 nm) could be responsible for the primary damage that occurs in the DNA. The reduction in the shoulder of the survival curve in wild type strains in indicative of induction of sub-lethal damage in this region of the curve. Analysing solar inactivation curves of the bacterial strains (normalised by spore dosimetry) together with those of the same strains irradiated with UV at 254 nm, it was evident that 254 nm is not the ideal wavelength for comparison. This analysis also indicated that in addition to damage to DNA, other factors are involved in the solar radiation inactivation of wild type strains. (author)

On Theft with Lethal Weapons in Criminal Law%论刑法中的携带凶器盗窃

Institute of Scientific and Technical Information of China (English)

安军

2012-01-01

我国刑法中携带凶器型盗窃的立法意图及模式为具体理解与适用提供了基准。作为规范构成要件要素的凶器,除了需要考察凶器的客观因素外,还必须考虑行为人的主观因素,即在具体的案件中应以客观的及主观的要素为根据综合判断。携带凶器的时间段应包括着手实行盗窃行为至盗窃罪构成要件完成（既遂）的全过程。在这一过程中,行为人认识到自己携带了凶器,认识到自己在盗窃他人财物,希望通过携带的凶器排除或阻止他人的反抗,以便非法占有他人财物。与普通盗窃相比,携带凶器型盗窃除了属于行为犯外,更具有抽象危险犯的特征,二者并行不悖。%In Chinese criminal law,the legislative intent and model of theft with lethal weapons provides a benchmark for specific understanding and application.As normative elements of constitutive requirements of lethal weapons,the behavior of subjective factors should also be considered in addition to the objective factors of the weapon;in other words,the judgment should be based on objective and subjective elements in specific cases.The period of carrying lethal weapons should be from the start of acting to execute theft to complete offense of theft.The subject recognized carrying lethal weapons and his stealing behaviors,wished to exclude or block resistance and occupy property of others by carrying lethal weapons in this process.Compared with ordinary theft,theft with lethal weapons has more features of abstract potential damage offense in addition to belonging to behavioral offense,two of which are not contradictary to each other.

Chloroquine Improves Survival and Hematopoietic Recovery After Lethal Low-Dose-Rate Radiation

International Nuclear Information System (INIS)

Lim Yiting; Hedayati, Mohammad; Merchant, Akil A.; Zhang Yonggang; Yu, Hsiang-Hsuan M.; Kastan, Michael B.; Matsui, William; DeWeese, Theodore L.

2012-01-01

Purpose: We have previously shown that the antimalarial agent chloroquine can abrogate the lethal cellular effects of low-dose-rate (LDR) radiation in vitro, most likely by activating the ataxia-telangiectasia mutated (ATM) protein. Here, we demonstrate that chloroquine treatment also protects against lethal doses of LDR radiation in vivo. Methods and Materials: C57BL/6 mice were irradiated with a total of 12.8 Gy delivered at 9.4 cGy/hour. ATM null mice from the same background were used to determine the influence of ATM. Chloroquine was administered by two intraperitoneal injections of 59.4 μg per 17 g of body weight, 24 hours and 4 hours before irradiation. Bone marrow cells isolated from tibia, fibula, and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retroorbital injection. Chimerism was assessed by flow cytometry. In vitro methylcellulose colony-forming assay of whole bone marrow cells and fluorescence activated cell sorting analysis of lineage depleted cells were used to assess the effect of chloroquine on progenitor cells. Results: Mice pretreated with chloroquine before radiation exhibited a significantly higher survival rate than did mice treated with radiation alone (80% vs. 31%, p = 0.0026). Chloroquine administration before radiation did not affect the survival of ATM null mice (p = 0.86). Chloroquine also had a significant effect on the early engraftment of bone marrow cells from the irradiated donor mice 6 weeks after transplantation (4.2% vs. 0.4%, p = 0.015). Conclusion: Chloroquine administration before radiation had a significant effect on the survival of normal but not ATM null mice, strongly suggesting that the in vivo effect, like the in vitro effect, is also ATM dependent. Chloroquine improved the early engraftment of bone marrow cells from LDR-irradiated mice, presumably by protecting the progenitor cells from radiation injury. Chloroquine thus could serve as a very useful drug for protection

Chemical and non-chemical stressors affecting childhood obesity: a systematic scoping review.

Science.gov (United States)

Lichtveld, Kim; Thomas, Kent; Tulve, Nicolle S

2018-01-01

Childhood obesity in the United States has doubled over the last three decades and currently affects 17% of children and adolescents. While much research has focused on individual behaviors impacting obesity, little research has emphasized the complex interactions of numerous chemical and non-chemical stressors found in a child's environment and how these interactions affect a child's health and well-being. The objectives of this systematic scoping review were to (1) identify potential chemical stressors in the context of non-chemical stressors that impact childhood obesity; and, (2) summarize our observations for chemical and non-chemical stressors in regards to child-specific environments within a community setting. A review was conducted to identify chemical and non-chemical stressors related to childhood obesity for the childhood life stages ranging from prenatal to adolescence. Stressors were identified and grouped into domains: individual behaviors, family/household behaviors, community stressors, and chemical exposures. Stressors were related to the child and the child's everyday environments and used to characterize child health and well-being. This review suggests that the interactions of chemical and non-chemical stressors are important for understanding a child's overall health and well-being. By considering these relationships, the exposure science research community can better design and implement strategies to reduce childhood obesity.

Expression and Genetic Variation in Neuroendocrine Signaling Pathways in Lethal and Nonlethal Prostate Cancer among Men Diagnosed with Localized Disease.

Science.gov (United States)

Lu, Donghao; Carlsson, Jessica; Penney, Kathryn L; Davidsson, Sabina; Andersson, Swen-Olof; Mucci, Lorelei A; Valdimarsdóttir, Unnur; Andrén, Ove; Fang, Fang; Fall, Katja

2017-12-01

Background: Recent data suggest that neuroendocrine signaling pathways may play a role in the progression of prostate cancer, particularly for early-stage disease. We aimed to explore whether expression of selected genes in the adrenergic, serotoninergic, glucocorticoid, and dopaminergic pathways differs in prostate tumor tissue from men with lethal disease compared with men with nonlethal disease. Methods: On the basis of the Swedish Watchful Waiting Cohort, we included 511 men diagnosed with incidental prostate cancer through transurethral resection of the prostate during 1977-1998 with follow-up up to 30 years. For those with tumor tissue ( N = 262), we measured mRNA expression of 223 selected genes included in neuroendocrine pathways. Using DNA from normal prostate tissue ( N = 396), we genotyped 36 SNPs from 14 receptor genes. Lethal prostate cancer was the primary outcome in analyses with pathway gene expression and genetic variants. Results: Differential expression of genes in the serotoninergic pathway was associated with risk of lethal prostate cancer ( P = 0.007); similar but weaker associations were noted for the adrenergic ( P = 0.014) and glucocorticoid ( P = 0.020) pathways. Variants of the HTR2A (rs2296972; P = 0.002) and NR3CI (rs33388; P = 0.035) genes (within the serotoninergic and glucocorticoid pathways) were associated with lethal cancer in overdominant models. These genetic variants were correlated with expression of several genes in corresponding pathways ( P pathways, particularly serotoninergic pathway, are associated with lethal outcome in the natural course of localized prostate cancer. Impact: This study provides evidence of the role of neuroendocrine pathways in prostate cancer progression that may have clinical utility. Cancer Epidemiol Biomarkers Prev; 26(12); 1781-7. ©2017 AACR . ©2017 American Association for Cancer Research.

Non-lethality in reality: a defence technology assessment of its political and military potential

NARCIS (Netherlands)

Orbons, J.B.J.

2013-01-01

Het gebruik van non-lethal weapons (NLW’s, niet-dodelijke wapens zoals traangas en plastic kogels) bij het winnen van hearts and minds van de bevolking is alleen effectief als de bevolking een politiek perspectief wordt geboden. Zonder een aanvaardbaar politiek perspectief worden NLW’s toenemend

CD4 T cell-mediated protection from lethal influenza: perforin and antibody-mediated mechanisms give a one-two punch.

Science.gov (United States)

Brown, Deborah M; Dilzer, Allison M; Meents, Dana L; Swain, Susan L

2006-09-01

The mechanisms whereby CD4 T cells contribute to the protective response against lethal influenza infection remain poorly characterized. To define the role of CD4 cells in protection against a highly pathogenic strain of influenza, virus-specific TCR transgenic CD4 effectors were generated in vitro and transferred into mice given lethal influenza infection. Primed CD4 effectors conferred protection against lethal infection over a broad range of viral dose. The protection mediated by CD4 effectors did not require IFN-gamma or host T cells, but did result in increased anti-influenza Ab titers compared with untreated controls. Further studies indicated that CD4-mediated protection at high doses of influenza required B cells, and that passive transfer of anti-influenza immune serum was therapeutic in B cell-deficient mice, but only when CD4 effectors were present. Primed CD4 cells also acquired perforin (Pfn)-mediated cytolytic activity during effector generation, suggesting a second mechanism used by CD4 cells to confer protection. Pfn-deficient CD4 effectors were less able to promote survival in intact BALB/c mice and were unable to provide protection in B cell-deficient mice, indicating that Ab-independent protection by CD4 effectors requires Pfn. Therefore, CD4 effectors mediate protection to lethal influenza through at least two mechanisms: Pfn-mediated cytotoxicity early in the response promoted survival independently of Ab production, whereas CD4-driven B cell responses resulted in high titer Abs that neutralized remaining virus.

Low survival of mice following lethal gamma-irradiation after administration of inhibitors of prostaglandin synthesis

International Nuclear Information System (INIS)

Hofer, M.; Pospisil, M.; Tkadlecek, L.; Viklicka, S.; Pipalova, I.; Hola, J.

1992-01-01

An impairment was observed of the survival of mice subjected to whole-body gamma-irradiation with a lethal dose of 10 Gy and treated with a repeated postirradiation administration of the prostaglandin synthesis inhibitors (PGSIs) indomethacin or diclofenac. Morphological examination of the gastrointestinal tract and estimation of the blood loss into its lumen in animals treated with diclofenac did not show serious damage such as hemorrhages or perforation, but revealed structural injury to the intestinal mucosa indicating inflammatory processes. The lesions found are supposed to be connected with increased intestinal permeability which leads to endotoxin escape from the gut and a subsequent increased mortality rate of irradiated animals. It may be concluded that PGSIs are not suitable for the management of radiation sickness after an exposure to lethal doses of ionizing radiation. (author) 2 tabs., 4 figs., 20 refs

Interactive lethal and mutagenic effects of ultraviolet light and bleomycin in yeast: synergism or antagonism?

Science.gov (United States)

Lillo, O L; Severgnini, A A; Nunes, E M

1997-11-01

The mutagenic interactions of ultraviolet light and bleomycin in haploid populations of Saccharomyces cerevisiae were analyzed. Survival and mutation frequency as a function of different bleomycin concentrations after one conditioning dose of UV radiation were determined. Furthermore, corresponding interaction functions and sensitization factors were calculated. A synergistic interaction between UV light and bleomycin was shown for both lethal and mutagenic events when the cells were in nutrient broth during the treatments. Conversely, the interaction between UV light and bleomycin was antagonistic when the cells were in deionized water during the treatment. The magnitude of lethal and mutagenic interactions depends on dose, and thus presumably on the number of lesions. The observed interactions between UV light and bleomycin suggest that the mechanism that is most likely involved is the induction of repair systems with different error probabilities during the delay of cell division.

Minimally invasive transcriptome profiling in salmon: detection of biological response in rainbow trout caudal fin following exposure to environmental chemical contaminants.

Science.gov (United States)

Veldhoen, Nik; Stevenson, Mitchel R; Skirrow, Rachel C; Rieberger, Kevin J; van Aggelen, Graham; Meays, Cynthia L; Helbing, Caren C

2013-10-15

An increasing number of anthropogenic chemicals have demonstrated potential for disruption of biological processes critical to normal growth and development of wildlife species. Both anadromous and freshwater salmon species are at risk of exposure to environmental chemical contaminants that may affect migratory behavior, environmental fitness, and reproductive success. A sensitive metric in determination of the presence and impact of such environmental chemical contaminants is through detection of changes in the status of gene transcript levels using a targeted quantitative real-time polymerase chain reaction assay. Ideally, the wildlife assessment strategy would incorporate conservation-centered non-lethal practices. Herein, we describe the development of such an assay for rainbow trout, Oncorhynchus mykiss, following an acute 96 h exposure to increasing concentrations of either 17α-ethinyl estradiol or cadmium. The estrogenic screen included measurement of mRNA encoding estrogen receptor α and β isoforms, vitellogenin, vitelline envelope protein γ, cytochrome p450 family 19 subfamily A, aryl hydrocarbon receptor, and the stress indicator, catalase. The metal exposure screen included evaluation of the latter two mRNA transcripts along with those encoding the metallothionein A and B isoforms. Exposure-dependent transcript abundance profiles were detected in both liver and caudal fin supporting the use of the caudal fin as a non-lethally obtained tissue source. The potential for both transcriptome profiling and genotypic sex determination from fin biopsy was extended, in principle, to field-captured Chinook salmon (Oncorhynchus tshawytscha). Copyright © 2013 Elsevier B.V. All rights reserved.

Noninvasive risk stratification of lethal ventricular arrhythmias and sudden cardiac death after myocardial infarction

Directory of Open Access Journals (Sweden)

Kenji Yodogawa, MD

2014-08-01

Full Text Available Prediction of lethal ventricular arrhythmias leading to sudden cardiac death is one of the most important and challenging problems after myocardial infarction (MI. Identification of MI patients who are prone to ventricular tachyarrhythmias allows for an indication of implantable cardioverter-defibrillator placement. To date, noninvasive techniques such as microvolt T-wave alternans (MTWA, signal-averaged electrocardiography (SAECG, heart rate variability (HRV, and heart rate turbulence (HRT have been developed for this purpose. MTWA is an indicator of repolarization abnormality and is currently the most promising risk-stratification tool for predicting malignant ventricular arrhythmias. Similarly, late potentials detected by SAECG are indices of depolarization abnormality and are useful in risk stratification. However, the role of SAECG is limited because of its low predictive accuracy. Abnormal HRV and HRT patterns reflect autonomic disturbances, which may increase the risk of lethal ventricular arrhythmias, but the existing evidence is insufficient. Further studies of noninvasive assessment may provide a new insight into risk stratification in post-MI patients.

LSD1 activates a lethal prostate cancer gene network independently of its demethylase function.

Science.gov (United States)

Sehrawat, Archana; Gao, Lina; Wang, Yuliang; Bankhead, Armand; McWeeney, Shannon K; King, Carly J; Schwartzman, Jacob; Urrutia, Joshua; Bisson, William H; Coleman, Daniel J; Joshi, Sunil K; Kim, Dae-Hwan; Sampson, David A; Weinmann, Sheila; Kallakury, Bhaskar V S; Berry, Deborah L; Haque, Reina; Van Den Eeden, Stephen K; Sharma, Sunil; Bearss, Jared; Beer, Tomasz M; Thomas, George V; Heiser, Laura M; Alumkal, Joshi J

2018-05-01

Medical castration that interferes with androgen receptor (AR) function is the principal treatment for advanced prostate cancer. However, clinical progression is universal, and tumors with AR-independent resistance mechanisms appear to be increasing in frequency. Consequently, there is an urgent need to develop new treatments targeting molecular pathways enriched in lethal prostate cancer. Lysine-specific demethylase 1 (LSD1) is a histone demethylase and an important regulator of gene expression. Here, we show that LSD1 promotes the survival of prostate cancer cells, including those that are castration-resistant, independently of its demethylase function and of the AR. Importantly, this effect is explained in part by activation of a lethal prostate cancer gene network in collaboration with LSD1's binding protein, ZNF217. Finally, that a small-molecule LSD1 inhibitor-SP-2509-blocks important demethylase-independent functions and suppresses castration-resistant prostate cancer cell viability demonstrates the potential of LSD1 inhibition in this disease.

The chemical evolution of galaxies

International Nuclear Information System (INIS)

Chiosi, Cesare

1986-01-01

The chemical evolution of galaxies is reviewed with particular attention to the theoretical interpretation of the distribution and abundances of elements in stars and the interstellar medium. The paper was presented to the conference on ''The early universe and its evolution'', Erice, Italy, 1986. The metallicity distribution of the solar vicinity, age metallicity relationship, abundance gradients in the galaxy, external galaxies, star formation and evolution, major sites of nucleosynthesis, yields of chemical elements, chemical models, and the galactic disk, are all discussed. (U.K.)

ATM inhibition induces synthetic lethality and enhances sensitivity of PTEN-deficient breast cancer cells to cisplatin.

Science.gov (United States)

Li, Ke; Yan, Huaying; Guo, Wenhao; Tang, Mei; Zhao, Xinyu; Tong, Aiping; Peng, Yong; Li, Qintong; Yuan, Zhu

2018-05-01

PTEN deficiency often causes defects in DNA damage repair. Currently, effective therapies for breast cancer are lacking. ATM is an attractive target for cancer treatment. Previous studies suggested a synthetic lethality between PTEN and PARP. However, the synthetically lethal interaction between PTEN and ATM in breast cancer has not been reported. Moreover, the mechanism remains elusive. Here, using KU-60019, an ATM kinase inhibitor, we investigated ATM inhibition as a synthetically lethal strategy to target breast cancer cells with PTEN defects. We found that KU-60019 preferentially sensitizes PTEN-deficient MDA-MB-468 breast cancer cells to cisplatin, though it also slightly enhances sensitivity of PTEN wild-type breast cancer cells. The increased cytotoxic sensitivity is associated with apoptosis, as evidenced by flow cytometry and PARP cleavage. Additionally, the increase of DNA damage accumulation due to the decreased capability of DNA repair, as indicated by γ-H2AX and Rad51 foci, also contributed to this selective cytotoxicity. Mechanistically, compared with PTEN wild-type MDA-MB-231 cells, PTEN-deficient MDA-MB-468 cells have lower level of Rad51, higher ATM kinase activity, and display the elevated level of DNA damage. Moreover, these differences could be further enlarged by cisplatin. Our findings suggest that ATM is a promising target for PTEN-defective breast cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

Determination of the Median Lethal Dose and Electrophoretic Pattern of Hottentotta saulcyi (Scorpiones, Buthidae Scorpion Venom

Directory of Open Access Journals (Sweden)

ErsenAydın Yağmur

2015-10-01

Full Text Available Background: In this study, we investigated the lethal potency, electrophoretic protein pattern and in vivo effects of Hottentotta saulcyi scorpion venom in mice.Methods: Scorpions were collected at night, by using a UV lamp from Mardin Province, Turkey. Venom was obtained from mature H. saulcyi scorpions by electrical stimulation of the telson. The lethality of the venom was determined by i.v. injections using Swiss mice. In vivo effects of the venom were assessed by using the intraperitoneal route (ip injections into mice (20±1g and monitored for 24 h. The protein profiles of the scorpion venom were analyzed by NuPAGE® Novex® 4–12 % gradient Bis-Tris gel followed by Coomassie blue staining.Results: The lethal assay of the venom was 0.73 mg/kg in mice. We determined the electrophoretic protein pattern of this scorpion venom to be 4, 6, 9, 31, 35, 40, 46 and 69 kDa by SDS-PAGE. Analysis of electrophoresis indicated that H. saulcyi scorpion intoxicated mice exhibited autonomic nervous system symptoms (tachypnea, restlessness, hyperexcitability, convulsions, salivation, lacrimation, weakness.Conclusions: Hottentotta saulcyi scorpion venom includes short-chain neurotoxins and long-chain neurotoxins according to the electrophoretic protein patterns. The stings of H. saulcyi scorpion must be considered of risk for humans in the southeastern region, Turkey.

Extra lethal damage due to residual incompletely repaired sublethal damage in hyperfractionated and continuous radiation treatment

Energy Technology Data Exchange (ETDEWEB)

Chen, J.; van de Geijn, J.; Goffman, T. (ROB, DCT, NCI, NIH, Bethesda, Maryland 20892 (US))

1991-05-01

In the conventional linear--quadratic model of single-dose response, the {alpha} and {beta} terms reflect lethal damage created {ital during} the delivery of a dose, from two different presumed molecular processes, one linear with dose, the other quadratic. With the conventional one-fraction-per-day (or less) regimens, the sublethal damage (SLD), presumably repairing exponentially over time, is essentially completely fixed by the time of the next dose of radiation. If this assumption is true, the effects of subsequent fractions of radiation should be independent, that is, there should be little, if any, reversible damage left from previous fractions, at the time of the next dose. For multiple daily fractions, or for the limiting case, continuous radiation, this simplification may overlook damaged cells that have had insufficient time for repair. A generalized method is presented for accounting for extra lethal damage (ELD) arising from such residual SLD for hyperfractionation and continuous irradiation schemes. It may help to predict differences in toxicity and tumor control, if any, obtained with unconventional'' treatment regimens. A key element in the present model is the finite size and the dynamic character of the pool of sublethal damage. Besides creating the usual linear and quadratic components of lethal damage, each new fraction converts a certain fraction of the existing SLD into ELD, and creates some new SLD.

Extra lethal damage due to residual incompletely repaired sublethal damage in hyperfractionated and continuous radiation treatment

International Nuclear Information System (INIS)

Chen, J.; van de Geijn, J.; Goffman, T.

1991-01-01

In the conventional linear--quadratic model of single-dose response, the α and β terms reflect lethal damage created during the delivery of a dose, from two different presumed molecular processes, one linear with dose, the other quadratic. With the conventional one-fraction-per-day (or less) regimens, the sublethal damage (SLD), presumably repairing exponentially over time, is essentially completely fixed by the time of the next dose of radiation. If this assumption is true, the effects of subsequent fractions of radiation should be independent, that is, there should be little, if any, reversible damage left from previous fractions, at the time of the next dose. For multiple daily fractions, or for the limiting case, continuous radiation, this simplification may overlook damaged cells that have had insufficient time for repair. A generalized method is presented for accounting for extra lethal damage (ELD) arising from such residual SLD for hyperfractionation and continuous irradiation schemes. It may help to predict differences in toxicity and tumor control, if any, obtained with ''unconventional'' treatment regimens. A key element in the present model is the finite size and the dynamic character of the pool of sublethal damage. Besides creating the usual linear and quadratic components of lethal damage, each new fraction converts a certain fraction of the existing SLD into ELD, and creates some new SLD

Lethal and Sublethal Effects of Fenpropathrin on the Biological Performance of Scolothrips longicornis (Thysanoptera: Thripidae)

DEFF Research Database (Denmark)

Pakyari, Hajar; Enkegaard, Annie

2013-01-01

Determination of negative nontarget effects of pesticides on beneficial organisms by measuring only lethal effects is likely to underestimate effects of sublethal doses. In this study, the sublethal effects of fenpropathrin on the predatory thrips Scolothrips longicornis Priesner (Thysanoptera: T...

Radiation and chemically induced potentially lethal lesions in noncycling mammalian cells: recovery analysis in terms of x-ray- and ultraviolet-like-systems

International Nuclear Information System (INIS)

Hahn, G.M.

1975-01-01

Recovery from and fixation of potentially lethal damage after exposure of Chinese hamster cells to uv and to x irradiation were investigated, as was recovery after exposure to chemotherapeutic agents. Recovery after uv radiation has a T/sub 1 / 2 / of about 20 hr; the fraction of cells able to undergo recovery depends upon nutritional factors both before and after exposure. After x irradiation, recovery proceeds with a T/sub 1 / 2 / of approximately 2 hr and is much less influenced by nutritional factors. Fixation after serum stimulation has a T/sub 1 / 2 / of 3 to 4 hr in uv-irradiated cells, a T/sub 1 / 2 / of 30 min in x-irradiated cells. Recovery kinetics after nitrogen mustard and bleomycin exposures mimic those for x-ray exposure; after methyl methane sulfonate the kinetics are mainly uv-like, though with an x-ray-like component. Recovery by cells with BUdR-substituted DNA and irradiated with visible light is primarily x-ray-like, though with a uv-like component. There is no recovery by cells exposed to adriamycin or to 1,3-bis(2-chloroethyl)-1-nitrosourea

Modification of radiation-induced sex-linked recessive lethal mutation frequency by tocopherol

International Nuclear Information System (INIS)

Beckman, C.; Roy, R.M.; Sproule, A.

1982-01-01

The present study evaluates the effect of supplementing culture medium with α-tocopherol acetate on the yield of sex-linked recessive lethal mutants induced by X-irradiation in mature sperm of Drosophila. Although tocopherol treatment of males had no impact on the yield of mutations, a drastic reduction in mutation frequency was observed when irradiated males were mated to females raised and subsequently maintained on tocopherol-enriched diet. (orig./MG)

The effects of radiation dose-rate and quality on the induction of dominant lethals in mouse spermatids

International Nuclear Information System (INIS)

Searle, A.G.; Beechey, G.V.

1981-01-01

Hybrid male mice were given 3 Gy (300 rad) doses of X- or γ-irradiation at dose-rates of either 0.6 or 0.002 Gy/min for each radiation. Germ-cells treated as spermatids were tested for dominant lethality. Effects on spermatogonia were evaluated by studying testis-weight, sperm-count and sperm abnormalities. The rate of induction of dominant lethal mutations was 2.1 times as high after acute X-irradiation as after protracted γ-irradiation. Most of this difference resulted from the change in radiation quality, since the relative effectiveness of X- versus γ-irradiation was 1.9 at low and 1.6 at high dose rates. For each radiation, however, fewer dominant lethals were induced at low dose-rates than at high (low/high ratios of 0.8 and 0.9 respectively) although differences did not reach a significant level. There were no statistically significant effects of dose rate on testis-weight of sperm-count in the X-ray series, but there were significantly less severe effects on both with protraction of the γ-irradiation. Evidence for effects of radiation quality on these characters was conflicting. Frequencies of abnormal spermatozoa were markedly increased 7 weeks after irradiation but there were no consistent effects of radiation intensity or quality. (orig.)

Novel synthetic lethality screening method identifies TIP60-dependent radiation sensitivity in the absence of BAF180.

Science.gov (United States)

Hopkins, Suzanna R; McGregor, Grant A; Murray, Johanne M; Downs, Jessica A; Savic, Velibor

2016-10-01

In recent years, research into synthetic lethality and how it can be exploited in cancer treatments has emerged as major focus in cancer research. However, the lack of a simple to use, sensitive and standardised assay to test for synthetic interactions has been slowing the efforts. Here we present a novel approach to synthetic lethality screening based on co-culturing two syngeneic cell lines containing individual fluorescent tags. By associating shRNAs for a target gene or control to individual fluorescence labels, we can easily follow individual cell fates upon siRNA treatment and high content imaging. We have demonstrated that the system can recapitulate the functional defects of the target gene depletion and is capable of discovering novel synthetic interactors and phenotypes. In a trial screen, we show that TIP60 exhibits synthetic lethality interaction with BAF180, and that in the absence of TIP60, there is an increase micronuclei dependent on the level of BAF180 loss, significantly above levels seen with BAF180 present. Moreover, the severity of the interactions correlates with proxy measurements of BAF180 knockdown efficacy, which may expand its usefulness to addressing synthetic interactions through titratable hypomorphic gene expression. Copyright © 2016. Published by Elsevier B.V.

Insect radiosensitivity: dose curves and dose-fractionation studies of dominant lethal mutations in the mature sperm of 4 insect species

International Nuclear Information System (INIS)

LaChance, L.E.; Graham, C.K.

1984-01-01

Males of 4 species of insects: Musca domestica L. (housefly) (Diptera), Oncopeltus fasciatus (Dallas) (milkweed bug) (Hemiptera), Anagasta kuhniella (Zeller) (mealmoth) (Lepidoptera) and Heliothis virescens (Fab.) (tobacco budworm) (Lepidoptera) were irradiated as adults. Dose-response curves for the induction of dominant lethal mutations in the mature sperm were constructed. The curves were analyzed mathematically and compared with theoretical computer simulated curves requiring 1, 2, 4, 8 and 16 'hits' for the induction of a dominant lethal mutation. The 4 species belonging to 3 different orders of insects showed a wide range in radiation sensitivity and vastly different dose-response curves. When the data were analyzed by several mathematical models the authors found that a logistic response curve gave reasonably good fit with vastly different parameters for the 4 species. Dose-fractionation experiments showed no reduction in the frequency of lethal mutations induced in any species when an acute dose was fractionated into 2 equal exposures separated by an 8-h period. (Auth.)

Relationship between physico-chemical characteristics and potential toxicity of PM10.

Science.gov (United States)

Megido, Laura; Suárez-Peña, Beatriz; Negral, Luis; Castrillón, Leonor; Suárez, Susana; Fernández-Nava, Yolanda; Marañón, Elena

2016-11-01

PM10 was sampled at a suburban location affected by traffic and industry in the north of Spain. The samples were analysed to determine the chemical components of PM10 (organic and elemental carbon, soluble chemical species and metals). The aim of this study was to assess the toxicity of PM10 in terms of the bulk analysis and the physico-chemical properties of the particles. Total carbon, sulphates, ammonium, chlorides and nitrates were found to be the major constituents of PM10. The contribution of the last of these was found to increase significantly with PM10 concentration (Pearson coefficient correlation of 0.7, p-value major risk to human health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mercury monitoring in fish using a non-lethal tissue biopsy method

Science.gov (United States)

Ackerson, J; Schmitt, Christopher J.; McKee, J; Brumbaugh, W. G.

2010-01-01

The occurrence of mercury in fish is well-known and often occurs at levels that warrant restricted consumption by sensitive human populations. Because of this, local wildlife and health agencies have developed monitoring programs to identify the magnitude of fish contamination and changes through time. Monitoring mercury levels in fish typically requires killing fish for removal of a fillet. Recently, researchers have proposed the use of a non-lethal tissue biopsy plug method as a surrogate for analysis of the entire fillet.

Bipyridine (2,2′-dipyridyl) potentiates Escherichia coli lethality induced by nitrogen mustard mechlorethamine

International Nuclear Information System (INIS)

De Alencar, T.A.M.; Wilmart-Gonçalves, T.C.; Vidal, L.S.; Fortunato, R.S.; Leitão, A.C.; Lage, C.

2014-01-01

Highlights: • Reduction of Fe 2+ ensues a respiratory burst to reduce the oxidized iron pool. • Through Harber–Weiss recycling, superoxide electrons can reduce oxidized iron. • Redox imbalance sensitized repair proficient Escherichia coli to mustard lethal crosslinks. • A stronger synergism impacted survival of a superoxide dismutase-deficient strain. • Anti-cancer cocktails added of an iron chelator may impact hypoxia and genotoxicity. - Abstract: Alkylating agents are used in anti-tumor chemotherapy because they bind covalently to DNA and generate adducts that may lead to cell death. Bifunctional (HN2) and monofunctional (HN1) nitrogen are two such agents, and HN2 was the first drug successfully employed in anti-leukemia chemotherapy. Currently, HN2 is used either alone or combined with other drugs to treat Hodgkin's disease. It is well known that several crosslinking agents require metabolic activation via reactive oxygen species (ROS) to exert their lethal effects. The objective of this work was therefore to determine whether the abovementioned mustards would also require metabolic activation to exert lethal action against Escherichia coli. For this purpose, we measured survival following exposure to HN2 in E. coli strains that were deficient in nucleotide excision repair (uvrA NER mutant), base excision repair (xthA nfo nth fpg BER mutant) or superoxide dismutase (sodAB mutant) activity. We also performed the same experiments in cells pretreated with an iron chelator (2,2′-dipyridyl, DIP). The NER and BER mutants were only sensitive to HN2 treatment (survival rates similar to those of the wild-type were achieved with 5-fold lower HN2 doses). However, wild-type and sodAB strains were not sensitive to treatment with HN2. In all tested strains, survival dropped by 2.5-fold following pretreatment with DIP compared to treatment with HN2 alone. Furthermore, DIP treatment increased ROS generation in both wild type and sodAB-deficient strains. Based

Bipyridine (2,2′-dipyridyl) potentiates Escherichia coli lethality induced by nitrogen mustard mechlorethamine

Energy Technology Data Exchange (ETDEWEB)

De Alencar, T.A.M.; Wilmart-Gonçalves, T.C.; Vidal, L.S.; Fortunato, R.S.; Leitão, A.C. [Laboratório de Radiobiologia Molecular (Brazil); Lage, C., E-mail: claudia_lage_dna@yahoo.com.br [Laboratório de Radiações em Biologia (Brazil)

2014-07-15

Highlights: • Reduction of Fe{sup 2+} ensues a respiratory burst to reduce the oxidized iron pool. • Through Harber–Weiss recycling, superoxide electrons can reduce oxidized iron. • Redox imbalance sensitized repair proficient Escherichia coli to mustard lethal crosslinks. • A stronger synergism impacted survival of a superoxide dismutase-deficient strain. • Anti-cancer cocktails added of an iron chelator may impact hypoxia and genotoxicity. - Abstract: Alkylating agents are used in anti-tumor chemotherapy because they bind covalently to DNA and generate adducts that may lead to cell death. Bifunctional (HN2) and monofunctional (HN1) nitrogen are two such agents, and HN2 was the first drug successfully employed in anti-leukemia chemotherapy. Currently, HN2 is used either alone or combined with other drugs to treat Hodgkin's disease. It is well known that several crosslinking agents require metabolic activation via reactive oxygen species (ROS) to exert their lethal effects. The objective of this work was therefore to determine whether the abovementioned mustards would also require metabolic activation to exert lethal action against Escherichia coli. For this purpose, we measured survival following exposure to HN2 in E. coli strains that were deficient in nucleotide excision repair (uvrA NER mutant), base excision repair (xthA nfo nth fpg BER mutant) or superoxide dismutase (sodAB mutant) activity. We also performed the same experiments in cells pretreated with an iron chelator (2,2′-dipyridyl, DIP). The NER and BER mutants were only sensitive to HN2 treatment (survival rates similar to those of the wild-type were achieved with 5-fold lower HN2 doses). However, wild-type and sodAB strains were not sensitive to treatment with HN2. In all tested strains, survival dropped by 2.5-fold following pretreatment with DIP compared to treatment with HN2 alone. Furthermore, DIP treatment increased ROS generation in both wild type and sodAB-deficient strains

An orally available, small-molecule polymerase inhibitor shows efficacy against a lethal morbillivirus infection in a large animal model.

Science.gov (United States)

Krumm, Stefanie A; Yan, Dan; Hovingh, Elise S; Evers, Taylor J; Enkirch, Theresa; Reddy, G Prabhakar; Sun, Aiming; Saindane, Manohar T; Arrendale, Richard F; Painter, George; Liotta, Dennis C; Natchus, Michael G; von Messling, Veronika; Plemper, Richard K

2014-04-16

Measles virus is a highly infectious morbillivirus responsible for major morbidity and mortality in unvaccinated humans. The related, zoonotic canine distemper virus (CDV) induces morbillivirus disease in ferrets with 100% lethality. We report an orally available, shelf-stable pan-morbillivirus inhibitor that targets the viral RNA polymerase. Prophylactic oral treatment of ferrets infected intranasally with a lethal CDV dose reduced viremia and prolonged survival. Ferrets infected with the same dose of virus that received post-infection treatment at the onset of viremia showed low-grade viral loads, remained asymptomatic, and recovered from infection, whereas control animals succumbed to the disease. Animals that recovered also mounted a robust immune response and were protected against rechallenge with a lethal CDV dose. Drug-resistant viral recombinants were generated and found to be attenuated and transmission-impaired compared to the genetic parent virus. These findings may pioneer a path toward an effective morbillivirus therapy that could aid measles eradication by synergizing with vaccination to close gaps in herd immunity due to vaccine refusal.

Alternative methods for the median lethal dose (LD(50)) test: the up-and-down procedure for acute oral toxicity.

Science.gov (United States)

Rispin, Amy; Farrar, David; Margosches, Elizabeth; Gupta, Kailash; Stitzel, Katherine; Carr, Gregory; Greene, Michael; Meyer, William; McCall, Deborah

2002-01-01

The authors have developed an improved version of the up-and-down procedure (UDP) as one of the replacements for the traditional acute oral toxicity test formerly used by the Organisation for Economic Co-operation and Development member nations to characterize industrial chemicals, pesticides, and their mixtures. This method improves the performance of acute testing for applications that use the median lethal dose (classic LD50) test while achieving significant reductions in animal use. It uses sequential dosing, together with sophisticated computer-assisted computational methods during the execution and calculation phases of the test. Staircase design, a form of sequential test design, can be applied to acute toxicity testing with its binary experimental endpoints (yes/no outcomes). The improved UDP provides a point estimate of the LD50 and approximate confidence intervals in addition to observed toxic signs for the substance tested. It does not provide information about the dose-response curve. Computer simulation was used to test performance of the UDP without the need for additional laboratory validation.

Gastrointestinal decontamination in healthy and lethally irradiated monkeys

International Nuclear Information System (INIS)

Hendriks, W.D.H.

1980-01-01

In periods of extreme immunosuppression, infections which are often life-threatening, frequently occur. In an attempt to prevent such infections in lethally irradiated rhesus monkeys, the animals were subjected to strict reverse isolation prior to irradiation and administrated orally with nonabsorbable antibiotics in order to eliminate their microflora. The antibiotic combination was selected on the basis of a sensitivity test and was added to the liquid food supply. To rapidly achieve a high bactericidal concentration in the intestine, the same antibiotics were additionally given orally for 5 days. The microflora was reduced rapidly; within a few days sterile cultures were obtained. Particularly after discontinuation of the administration of the additional antibiotics were colonizations found. In contrast to colonizations persisting from the first day of treatment on, the first were rather easy to suppress. (Auth.)

A novel approach: chemical relational databases, and the role of the ISSCAN database on assessing chemical carcinogenicity.

Science.gov (United States)

Benigni, Romualdo; Bossa, Cecilia; Richard, Ann M; Yang, Chihae

2008-01-01

Mutagenicity and carcinogenicity databases are crucial resources for toxicologists and regulators involved in chemicals risk assessment. Until recently, existing public toxicity databases have been constructed primarily as "look-up-tables" of existing data, and most often did not contain chemical structures. Concepts and technologies originated from the structure-activity relationships science have provided powerful tools to create new types of databases, where the effective linkage of chemical toxicity with chemical structure can facilitate and greatly enhance data gathering and hypothesis generation, by permitting: a) exploration across both chemical and biological domains; and b) structure-searchability through the data. This paper reviews the main public databases, together with the progress in the field of chemical relational databases, and presents the ISSCAN database on experimental chemical carcinogens.

Fine-tuning synthesis of Yersinia pestis LcrV from runaway-like replication balanced-lethal plasmid in a Salmonella enterica serovar typhimurium vaccine induces protection against a lethal Y. pestis challenge in mice.

Science.gov (United States)

Torres-Escobar, Ascención; Juárez-Rodríguez, María Dolores; Gunn, Bronwyn M; Branger, Christine G; Tinge, Steven A; Curtiss, Roy

2010-06-01

A balanced-lethal plasmid expression system that switches from low-copy-number to runaway-like high-copy-number replication (pYA4534) was constructed for the regulated delayed in vivo synthesis of heterologous antigens by vaccine strains. This is an antibiotic resistance-free maintenance system containing the asdA gene (essential for peptidoglycan synthesis) as a selectable marker to complement the lethal chromosomal DeltaasdA allele in live recombinant attenuated Salmonella vaccines (RASVs) such as Salmonella enterica serovar Typhimurium strain chi9447. pYA4534 harbors two origins of replication, pSC101 and pUC (low and high copy numbers, respectively). The pUC replication origin is controlled by a genetic switch formed by the operator/promoter of the P22 cro gene (O/P(cro)) (P(R)), which is negatively regulated by an arabinose-inducible P22 c2 gene located on both the plasmid and the chromosome (araC P(BAD) c2). The absence of arabinose, which is unavailable in vivo, triggers replication to a high-copy-number plasmid state. To validate these vector attributes, the Yersinia pestis virulence antigen LcrV was used to develop a vaccine against plague. An lcrV sequence encoding amino acids 131 to 326 (LcrV196) was optimized for expression in Salmonella, flanked with nucleotide sequences encoding the signal peptide (SS) and the carboxy-terminal domain (CT) of beta-lactamase, and cloned into pYA4534 under the control of the P(trc) promoter to generate plasmid pYA4535. Our results indicate that the live Salmonella vaccine strain chi9447 harboring pYA4535 efficiently stimulated a mixed Th1/Th2 immune response that protected mice against lethal challenge with Y. pestis strain CO92 introduced through either the intranasal or subcutaneous route.

Fine-Tuning Synthesis of Yersinia pestis LcrV from Runaway-Like Replication Balanced-Lethal Plasmid in a Salmonella enterica Serovar Typhimurium Vaccine Induces Protection against a Lethal Y. pestis Challenge in Mice▿

Science.gov (United States)

Torres-Escobar, Ascención; Juárez-Rodríguez, María Dolores; Gunn, Bronwyn M.; Branger, Christine G.; Tinge, Steven A.; Curtiss, Roy

2010-01-01

A balanced-lethal plasmid expression system that switches from low-copy-number to runaway-like high-copy-number replication (pYA4534) was constructed for the regulated delayed in vivo synthesis of heterologous antigens by vaccine strains. This is an antibiotic resistance-free maintenance system containing the asdA gene (essential for peptidoglycan synthesis) as a selectable marker to complement the lethal chromosomal ΔasdA allele in live recombinant attenuated Salmonella vaccines (RASVs) such as Salmonella enterica serovar Typhimurium strain χ9447. pYA4534 harbors two origins of replication, pSC101 and pUC (low and high copy numbers, respectively). The pUC replication origin is controlled by a genetic switch formed by the operator/promoter of the P22 cro gene (O/Pcro) (PR), which is negatively regulated by an arabinose-inducible P22 c2 gene located on both the plasmid and the chromosome (araC PBAD c2). The absence of arabinose, which is unavailable in vivo, triggers replication to a high-copy-number plasmid state. To validate these vector attributes, the Yersinia pestis virulence antigen LcrV was used to develop a vaccine against plague. An lcrV sequence encoding amino acids 131 to 326 (LcrV196) was optimized for expression in Salmonella, flanked with nucleotide sequences encoding the signal peptide (SS) and the carboxy-terminal domain (CT) of β-lactamase, and cloned into pYA4534 under the control of the Ptrc promoter to generate plasmid pYA4535. Our results indicate that the live Salmonella vaccine strain χ9447 harboring pYA4535 efficiently stimulated a mixed Th1/Th2 immune response that protected mice against lethal challenge with Y. pestis strain CO92 introduced through either the intranasal or subcutaneous route. PMID:20308296

Genotoxicity test of irradiated spice mixture by dominant lethal test

Energy Technology Data Exchange (ETDEWEB)

Barna, J

1986-03-01

Dominant lethal test (DLT) was performed in Sprague Dawley male rats prefed with 25% irradiated spice mixture which was composed of 55% non-pungent ground paprika, 14% black pepper, 9% allspice, 9% coriander, 7% marjoram, 4% cumin, 2% nutmeg. Microbial count of the spice mixture was reduced with 15 kGy from a sup(60)Co source. Control groups received spice-free or untreated spice diet or were administered to cyclophosphamide i.p., respectively. DTL parameters altered significantly in the latter group but neither untreated nor irradiated spice mixture proved to be germ cell mutagens. 24 refs.; 8 figs.

Structure-Antioxidative and Anti-Inflammatory Activity Relationships of Purpurin and Related Anthraquinones in Chemical and Cell Assays

Directory of Open Access Journals (Sweden)

Woo Nam

2017-02-01

Full Text Available Anthraquinone (9,10-anthraquinone and several hydroxy derivatives, including purpurin (1,2,4-trihydroxyanthraquinone, anthrarufin (1,5-dihydroxyanthraquinone, and chrysazin (1,8-dihydroxyanthraquinone, were evaluated for antioxidative and anti-inflammatory activities in chemical assays and mammalian cells (murine macrophage RAW 264.7 cells. Several tests were used to assess their activities: 1,1-diphenyl-2-picrylhydrazyl (DPPH free radical; ABTS radical cation; hydrogen peroxide scavenging; reduction of potassium ferricyanide; chelation of ferrous ions; inhibition of lipid peroxidation; inhibition of nitric oxide generation; scavenging of the intracellular hydroxyl radical; expression of NLRP3 polypeptide for inflammasome assembly; and quantitation of proinflammatory cytokine interleukin 1β (IL-1β for inflammasome activation. The results show that purpurin, from the root of the madder plant (Rubia tinctorum L., exhibited the highest antioxidative activity in both chemical and cultured cell antioxidant assays. The antioxidative activities of the other three anthraquinones were lower than that of purpurin. In addition, purpurin could down-regulate NLRP3 inflammasome assembly and activation, suggesting that it might protect foods against oxidative damage and prevent in vivo oxidative stress and inflammation. Structure-activity relationships and the significance of the results for food quality and human health are discussed.

MHC Class II and Non-MHC Class II Genes Differentially Influence Humoral Immunity to Bacillus anthracis Lethal Factor and Protective Antigen

OpenAIRE

Garman, Lori; Dumas, Eric K.; Kurella, Sridevi; Hunt, Jonathan J.; Crowe, Sherry R.; Nguyen, Melissa L.; Cox, Philip M.; James, Judith A.; Farris, A. Darise

2012-01-01

Anthrax Lethal Toxin consists of Protective Antigen (PA) and Lethal Factor (LF), and current vaccination strategies focus on eliciting antibodies to PA. In human vaccination, the response to PA can vary greatly, and the response is often directed toward non-neutralizing epitopes. Variable vaccine responses have been shown to be due in part to genetic differences in individuals, with both MHC class II and other genes playing roles. Here, we investigated the relative contribution of MHC class I...

Thermodynamics of nuclear track chemical etching

Science.gov (United States)

Rana, Mukhtar Ahmed

2018-05-01

This is a brief paper with new and useful scientific information on nuclear track chemical etching. Nuclear track etching is described here by using basic concepts of thermodynamics. Enthalpy, entropy and free energy parameters are considered for the nuclear track etching. The free energy of etching is determined using etching experiments of fission fragment tracks in CR-39. Relationship between the free energy and the etching temperature is explored and is found to be approximately linear. The above relationship is discussed. A simple enthalpy-entropy model of chemical etching is presented. Experimental and computational results presented here are of fundamental interest in nuclear track detection methodology.

Reliability of non-lethal assessment methods of body composition and energetic status exemplified by applications to eel (Anguilla anguilla) and carp (Cyprinus carpio)

DEFF Research Database (Denmark)

Klefoth, Thomas; Skov, Christian; Aarestrup, Kim

2013-01-01

tNon-lethal assessments of proximate body composition of fish can help unravelling the physiologicaland condition-dependent mechanisms of individual responses to ecological challenges. Common non-lethal methods designed to index nutrient composition in fish include the relative condition factor (Kn......),bioelectric impedance-based assessments of body composition (BIA), and microwave-based “fat” meters(FM). Previous studies have revealed mixed findings as to the reliability of each of these. We compared theperformance of Kn, BIA and FM at different temperatures to predict energetic status of the whole bodiesof live eel...... approach isthe most suitable method to non-lethally estimate energetic status in both, carp and eel, whereas BIA is oflimited use for energetic measurements in the same species, in contrast to other reports in the literature...

Pregnancy continuation and organizational religious activity following prenatal diagnosis of a lethal fetal defect are associated with improved psychological outcome.

Science.gov (United States)

Cope, Heidi; Garrett, Melanie E; Gregory, Simon; Ashley-Koch, Allison

2015-08-01

The aim of the article is to examine the psychological impact, specifically symptoms of grief, post-traumatic stress and depression, in women and men who either terminated or continued a pregnancy following prenatal diagnosis of a lethal fetal defect. This project investigated a diagnostically homogeneous group composed of 158 women and 109 men who lost a pregnancy to anencephaly, a lethal neural tube defect. Participants completed the Perinatal Grief Scale, Impact of Event Scale - Revised and Beck Depression Inventory-II, which measure symptoms of grief, post-traumatic stress and depression, respectively. Demographics, religiosity and pregnancy choices were also collected. Gender-specific analysis of variance was performed for instrument total scores and subscales. Women who terminated reported significantly more despair (p = 0.02), avoidance (p = 0.008) and depression (p = 0.04) than women who continued the pregnancy. Organizational religious activity was associated with a reduction in grief (Perinatal Grief Scale subscales) in both women (p = 0.02, p = 0.04 and p = 0.03) and men (p = 0.047). There appears to be a psychological benefit to women to continue the pregnancy following a lethal fetal diagnosis. Following a lethal fetal diagnosis, the risks and benefits, including psychological effects, of termination and continuation of pregnancy should be discussed in detail with an effort to be as nondirective as possible. © 2015 John Wiley & Sons, Ltd.

Epithelial Plasticity in Castration-Resistant Prostate Cancer: Biology of the Lethal Phenotype

Science.gov (United States)

2011-07-01

647, cytokeratin (AbD Serotec #MCA 1907HT) labeled with Alexa 555, and Vimentin (BD Biosciences, San Jose , CA #550513) labeled with Alexa 488. Nuclear...importance of the transitional phenotypic state to lethal cancer biology. In: Proceedings of the Genitourinary Cancers Symposium; 5–7 March 2010; San ...resulting gene list was used to determine the significantly differentially expressed genes between AT3-M and AT3-T using the "Filtering on Volcano

Protective Monotherapy Against Lethal Ebola Virus Infection by a Potently Neutralizing Antibody

Science.gov (United States)

2016-07-11

were 49   identified and enrolled in VRC200 clinical trial #NCT00067054 after giving signed 50   informed consent . Peripheral blood mononuclear...illness 56   when administered one day after lethal challenge. Treatment with a single human 57   mAb suggests a simplified therapeutic strategy for...efforts to simplify the ZMapp regimen to contain fewer mAbs have not been successful in 75   the macaque EVD model (7). We sought to isolate

An evaluation of chemical photoreactivity and the relationship to phototoxicity.

Science.gov (United States)

Kleinman, Mark H; Smith, Mark D; Kurali, Edit; Kleinpeter, Sarah; Jiang, Kaina; Zhang, Yongxia; Kennedy-Gabb, Sonya A; Lynch, Anthony M; Geddes, Chris D

2010-11-01

The existing regulatory guidance for photosafety testing of new drug products states that studies are warranted for those chemicals that both absorb light in the range of 290-700 nm, and that are either applied locally/topically, or "reach" (EMEA)/"significantly partition" (FDA) to the skin or eyes. The initial in vitro study recommended for the assessment of phototoxic potential is the 3T3 Neutral Red Uptake (NRU) Assay. The current study was undertaken to establish superior triggers for the initiation of biological photosafety testing. In this study, photophysical and photochemical parameters for 40 drug or drug-like molecules were studied. Principal Component Analysis (PCA), Partial Least Squares-Discriminant Analysis (PLS-DA), and a fivefold cross-validation PLS algorithm were used to evaluate the relationship between subsets of photophysical and photochemical parameters with the 3T3 NRU PIF/MPE (Photo Irritation Factor/Mean Photo Effect) results. The parameters most indicative of a 3T3 NRU positive PIF or MPE score were the extent of degradation in solution, the quantum yield of formation of singlet oxygen and the relative formation of superoxide anion. The results demonstrate that while absorption of light is critical to the induction of a light-induced process, it is the resultant events that may be used to predict the 3T3 NRU assay result. It is therefore proposed that the trigger for photosafety testing be revised to include a molecular basis for photoreactivity. From this limited investigation, estimated thresholds leading to 3T3 NRU positive results due to photodegradation, formation of singlet oxygen quantum yield or a relative superoxide anion formation value are proposed. Copyright © 2010 Elsevier Inc. All rights reserved.

Lethal doses of ionizing radiation versus endogenous level of superoxide dismutase

Energy Technology Data Exchange (ETDEWEB)

Lipecka, K; Domanski, T; Dniaszewska, K; Grabowska, B; Pietrowicz, D; Lindner, P; Cisowska, B; Gorski, H [Military Medical Academy, Lodz (Poland). Inst. of Occupational Medicine

1982-06-22

The stability of superoxide dismutase (SOD) as well as its activity distribution in a human population were investigated. The SOD activity level of the erythrocytes proved to be an index for the endogenous SOD activity in the whole body. In a rat population, having similar SOD frequency distribution as a human population, the mortality due to acute irradiation depended on the SOD level; after a single acute dose approximating the lethal dose (LD/sub 50/30/) the survival depended distinctly on the endogenous SOD activity level.

Determination of gamma radiation lethal dose (LD50) and resveratrol cytotoxicity level in tumor cells line

International Nuclear Information System (INIS)

Magalhaes, Vanessa D.; Rogero, Sizue O.; Rogero, Jose R.; Cruz, Aurea S.

2011-01-01

Cancer is a disease with high incidence and it is considered a worldwide public health problem. Resveratrol is a polyphenol occurring naturally in a wide variety of plants according to response of ultraviolet radiation (UV) exposition or according to mechanical stress resulting of pathogens or chemical and physical agents. This polyphenol possesses a pharmacological activity of carcinogenesis inhibition in multiple levels. It also protects cells by scavenging the free radicals which are considered toxic products. These free radicals are formed of natural process of cell aging and also by incidence of ionizing radiation in the organism. Thus, resveratrol is considered as a cell radioprotector. On the other hand, in some elevated concentrations resveratrol may be considered as a radiosensitizing. The aim of this work was the determination of radiation lethal dose (LD 50 ) and also verifies the cytotoxicity level of resveratrol in tumor cells line: muco epidermoid pulmonary carcinoma cells (NCI-H292) and rhabdomyosarcoma cells (RD). The cytotoxicity test was performed by neutral red uptake assay. The results of resveratrol IC 50% in NCI-H292 cells was 192μM and in RD cells was 128μM; and RD cells gamma radiation LD 50 was 435Gy. (author)

Investigation of the lethal and behavioral effects of commercial insecticides on the parasitoid wasp Copidosoma truncatellum.

Science.gov (United States)

Ramos, Rodrigo S; de Araújo, Vitor C R; Pereira, Renata R; Martins, Júlio C; Queiroz, Obiratanea S; Silva, Ricardo S; Picanço, Marcelo C

2018-01-01

Copidosoma truncatellum (Hymenoptera: Encyrtidae) is an important parasitoid wasp of the soybean looper, Chrysodeixis includens, but its effectiveness can be severely curtailed by the application of certain insecticides. Therefore, to identify insecticides that are potentially compatible with C. truncatellum, the lethal and behavioral effects of nine chemicals used to control the soybean looper were evaluated for their toxicity to the wasp. Chlorantraniliprole, chlorfenapyr, flubendiamide, and indoxacarb were the least toxic insecticides to the parasitoid, resulting in mortalities of less than 25%. In contrast, cartap, deltamethrin, and methomyl caused 100% mortality, and acephate and spinosad caused 76% and 78% mortality, respectively. At least one of the detoxifying enzymes (monooxygenase, glutathione S-transferase, and/or esterases) may be involved in the mechanisms underlying the selectivity of chlorantraniliprole, chlorfenapyr, flubendiamide, and indoxacarb for the parasitoid based on the results for the insecticide plus synergist treatment. Changes in the behavioral patterns (walking time and resting time) of the parasitoid were found with exposure to acephate, flubendiamide, indoxacarb and methomyl, but behavioral avoidance was not observed. Our results indicate that the insecticides chlorantraniliprole and chlorfenapyr are the most suitable for inclusion in integrated pest management strategies for the control of C. includens. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sub-Lethal Dose of Shiga toxin 2 from Enterohemorrhagic Escherichia coli Affects Balance and Cerebellar Cythoarquitecture.

Directory of Open Access Journals (Sweden)

Luciana eD’Alessio

2016-02-01

Full Text Available Shiga toxin producing Escherichia coli may damage the central nervous system before or concomitantly to manifested hemolytic uremic syndrome symptoms. The cerebellum is frequently damaged during this syndrome, however the deleterious effects of Shiga toxin 2 has never been integrally reported by ultrastructural, physiological and behavioral means. The aim of this study was to determine the cerebellar compromise after intravenous administration of a sub-lethal dose of Shiga toxin 2 by measuring the cerebellar blood brain barrier permeability, behavioral task of cerebellar functionality (inclined plane test, and ultrastructural analysis (transmission electron microscope. Intravenous administration of vehicle (control group, sub-lethal dose of 0.5 ηg and 1 ηg of Stx2 per mouse were tested for behavioral and ultrastructural studies. A set of three independent experiments were performed for each study (n=6. Blood–Brain Barrier resulted damaged and consequently its permeability was significantly increased. Lower scores obtained in the inclined plane task denoted poor cerebellar functionality in comparison to their controls. The most significant lower score was obtained after 5 days of 1ηg of toxin administration. Transmission electron microscope micrographs from the Stx2-treated groups showed neurons with a progressive neurodegenerative condition in a dose dependent manner. As sub-lethal intravenous Shiga toxin 2 altered the blood brain barrier permeability in the cerebellum the toxin penetrated the cerebellar parenchyma and produced cell damaged with significant functional implications in the test balance.

Standardization of anti-lethal toxin potency test of antivenoms prepared from two different Agkistrodon halys venoms

Directory of Open Access Journals (Sweden)

K. H. Lee

2006-01-01

Full Text Available In Korea, antivenoms for the treatment of patients bitten by venomous snakes have been imported from Japan or China. Although there is cross-reactivity between these antibodies and venoms from snakes indigenous to Korea (e.g. Agkistrodon genus, protection is not optimal. Antivenoms specifically prepared to neutralize Korean snake venoms could be more effective, with fewer side effects. To this end, we established an infrastructure to develop national standards and created a standardized method to evaluate the efficacy of two horse-derived antivenoms using mouse lethal toxin test. Additionally, we determined the antivenoms neutralizing activity against lethal doses (LD50 of Agkistrodon halys (from Japan and Jiangzhe Agkistrodon halys (from China venoms. We also performed cross-neutralization tests using probit analysis on each pairing of venom and antivenom in order to check the possibility of using Jiangzhe A. halys venom as a substitute for A. halys venom, the current standard. Slope of A. halys venom with A. halys antivenom was 10.2 and that of A. halys venom with Jiangzhe A. halys antivenom was 9.6. However, Slope of Jiangzhe A. halys venom with A. halys antivenom was 4.7 while that of Jiangzhe A. halys venom with Jiangzhe A. halys antivenom was 11.5. Therefore, the significant difference in slope patterns suggests that Jiangzhe A. halys venom cannot be used as a substitute for the standard venom to test the anti-lethal toxin activity of antivenoms (p<0.05.

Non-allergic cutaneous reactions in airborne chemical sensitivity--a population based study

DEFF Research Database (Denmark)

Berg, Nikolaj Drimer; Linneberg, Allan; Thyssen, Jacob Pontoppidan

2011-01-01

the relationship between cutaneous reactions from patch testing and self-reported severity of chemical sensitivity to common airborne chemicals. A total of 3460 individuals participating in a general health examination, Health 2006, were patch tested with allergens from the European standard series and screened...... for chemical sensitivity with a standardised questionnaire dividing the participants into four severity groups of chemical sensitivity. Both allergic and non-allergic cutaneous reactions--defined as irritative, follicular, or doubtful allergic reactions--were analysed in relationship with severity of chemical...... most severe groups of self-reported sensitivity to airborne chemicals. When adjusting for confounding, associations were weakened, and only non-allergic cutaneous reactions were significantly associated with individuals most severely affected by inhalation of airborne chemicals (odds ratio = 2.5, p = 0...

Enhanced understanding of the relationship between chemical modification and mechanical properties of wood

Science.gov (United States)

Charles R. Frihart; Daniel J. Yelle; John Ralph; Robert J. Moon; Donald S. Stone; Joseph E. Jakes

2008-01-01

Chemical additions to wood often change its bulk properties, which can be determined using conventional macroscopic mechanical tests. However, the controlling interactions between chemicals and wood take place at and below the scale of individual cells and cell walls. To better understand the effects of chemical additions to wood, we have adapted and extended two...

When a Fly Has to Fly to Reproduce: Selection against Conditional Recessive Lethals in "Drosophila"

Science.gov (United States)

Plunkett, Andrea D.; Yampolsky, Lev Y.

2010-01-01

We propose an experimental model suitable for demonstrating allele frequency change in Drosophila melanogaster populations caused by selection against an easily scorable conditional lethal, namely recessive flightless alleles such as apterous and vestigial. Homozygotes for these alleles are excluded from reproduction because the food source used…

The Rise of Robots: The Military’s Use of Autonomous Lethal Force

Science.gov (United States)

2015-02-17

2 (2007): 91-106. Musandu , Nyagudi . “ Humanitarian Algorithms : A Codified Key Safety Switch Protocol for Lethal Autonomy.” Independent Researcher...proportionality.48 However, it is not clear that the proper discriminating sensor inputs are currently, or would ever be available to feed such algorithms ...proportionality algorithm , and the potential difficulties in terminating a robot vs. robot army war. Currently, many of these concerns are assumed away

The effects of oil sands wastewater on fish resulting from exposure to sub-lethal concentrations

International Nuclear Information System (INIS)

Birkholz, D.A.; Goudey, J.S.; Balch, G.C.; Nelson, L.R.; MacKinnon, M.

1995-01-01

Rainbow trout, Oncorhynchus mykiss, were exposed to sub-lethal concentrations of oil sands wastewater in flow through laboratory experiments as well as to artificial ponds containing sub-lethal concentrations of tailings pond water and fine tails in order to study the viability of the wet landscape remediation option. Large (200--300 g) fish were used for all the exposures in this preliminary study and the following data were collected: blood cell counts, sex hormone concentrations, sexual maturation, stress protein concentrations, PAH-metabolites in bile, condition factors, liver somatic indices, mixed function oxygenase induction, PAHs in muscle, external condition and the condition of internal organs. The data obtained from this study revealed no adverse effects upon fish during extended field exposures. Given similar exposure conditions in the release waters of a wet landscape reclamation, the data suggest that there may be no adverse effects upon fish, however, longer term studies, other indicator organisms and additional chronic tests should be conducted

Experimental aerosolized guinea pig-adapted Zaire ebolavirus (variant: Mayinga) causes lethal pneumonia in guinea pigs.

Science.gov (United States)

Twenhafel, N A; Shaia, C I; Bunton, T E; Shamblin, J D; Wollen, S E; Pitt, L M; Sizemore, D R; Ogg, M M; Johnston, S C

2015-01-01

Eight guinea pigs were aerosolized with guinea pig-adapted Zaire ebolavirus (variant: Mayinga) and developed lethal interstitial pneumonia that was distinct from lesions described in guinea pigs challenged subcutaneously, nonhuman primates challenged by the aerosol route, and natural infection in humans. Guinea pigs succumbed with significant pathologic changes primarily restricted to the lungs. Intracytoplasmic inclusion bodies were observed in many alveolar macrophages. Perivasculitis was noted within the lungs. These changes are unlike those of documented subcutaneously challenged guinea pigs and aerosolized filoviral infections in nonhuman primates and human cases. Similar to findings in subcutaneously challenged guinea pigs, there were only mild lesions in the liver and spleen. To our knowledge, this is the first report of aerosol challenge of guinea pigs with guinea pig-adapted Zaire ebolavirus (variant: Mayinga). Before choosing this model for use in aerosolized ebolavirus studies, scientists and pathologists should be aware that aerosolized guinea pig-adapted Zaire ebolavirus (variant: Mayinga) causes lethal pneumonia in guinea pigs. © The Author(s) 2014.

Feelings of women regarding end-of-life decision making after ultrasound diagnosis of a lethal fetal malformation.

Science.gov (United States)

Benute, Gláucia R G; Nomura, Roseli M Y; Liao, Adolfo W; Brizot, Maria de Lourdes; de Lucia, Mara C S; Zugaib, M

2012-08-01

this study investigated the feelings of women regarding end-of-life decision making after ultrasound diagnosis of a lethal fetal malformation. The aim of this study was to present the decision making process of women that chose for pregnancy termination and to present selected speeches of women about their feelings. open psychological interviews conducted by a psychologist immediately after the diagnosis of fetal malformation by ultrasound. Analysis of the results was performed through a content analysis technique. the study was carried out at a public university hospital in Brazil. 249 pregnant women who had received the diagnosis of a severe lethal fetal malformation. fetal anencephaly was the most frequent anomaly detected in 135 cases (54.3%). Termination of pregnancy was decided by 172 (69.1%) patients and legally authorised by the judiciary (66%). The reason for asking for termination was to reduce suffering in all of them. In the 77 women who chose not to terminate pregnancy (30.9%), the reasons were related to feelings of guilt (74%). the results support the importance of psychological counselling for couples when lethal fetal malformation is diagnosed. The act of reviewing moral and cultural values and elements of the unconscious provides assurance in the decision-making process and mitigates the risk of emotional trauma and guilt that can continue long after the pregnancy is terminated. Copyright © 2011 Elsevier Ltd. All rights reserved.

Acute and sub-lethal exposure to copper oxide nanoparticles causes oxidative stress and teratogenicity in zebrafish embryos.

Science.gov (United States)

Ganesan, Santhanamari; Anaimalai Thirumurthi, Naveenkumar; Raghunath, Azhwar; Vijayakumar, Savitha; Perumal, Ekambaram

2016-04-01

Nano-copper oxides are a versatile inorganic material. As a result of their versatility, the immense applications and usage end up in the environment causing a concern for the lifespan of various beings. The ambiguities surround globally on the toxic effects of copper oxide nanoparticles (CuO-NPs). Hence, the present study endeavored to study the sub-lethal acute exposure effects on the developing zebrafish embryos. The 48 hpf LC50 value was about 64 ppm. Therefore, we have chosen the sub-lethal dose of 40 and 60 ppm for the study. Accumulation of CuO-NPs was evidenced from the SEM-EDS and AAS analyzes. The alterations in the AChE and Na(+)/K(+)-ATPase activities disrupted the development process. An increment in the levels of oxidants with a concomitant decrease in the antioxidant enzymes confirmed the induction of oxidative stress. Oxidative stress triggered apoptosis in the exposed embryos. Developmental anomalies were observed with CuO-NPs exposure in addition to oxidative stress in the developing embryos. Decreased heart rate and hatching delay hindered the normal developmental processes. Our work has offered valuable data on the connection between oxidative stress and teratogenicity leading to lethality caused by CuO-NPs. A further molecular mechanism unraveling the uncharted connection between oxidative stress and teratogenicity will aid in the safe use of CuO-NPs. Copyright © 2015 John Wiley & Sons, Ltd.

Bypass of lethality with mosaic mice generated by Cre-loxP-mediated recombination.

Science.gov (United States)

Betz, U A; Vosshenrich, C A; Rajewsky, K; Müller, W

1996-10-01

The analysis of gene function based on the generation of mutant mice by homologous recombination in embryonic stem cells is limited if gene disruption results in embryonic lethality. Mosaic mice, which contain a certain proportion of mutant cells in all organs, allow lethality to be circumvented and the potential of mutant cells to contribute to different cell lineages to be analyzed. To generate mosaic animals, we used the bacteriophage P1-derived Cre-loxP recombination system, which allows gene alteration by Cre-mediated deletion of loxP-flanked gene segments. We generated nestin-cre transgenic mouse lines, which expressed the Cre recombinase under the control of the rat nestin promoter and its second intron enhancer. In crosses to animals carrying a loxP-flanked target gene, partial deletion of the loxP-flanked allele occurred before day 10.5 post coitum and was detectable in all adult organs examined, including germ-line cells. Using this approach, we generated mosaic mice containing cells deficient in the gamma-chain of the interleukin-2 receptor (IL-2R gamma); in these animals, the IL-2R gamma-deficient cells were underrepresented in the thymus and spleen. Because mice deficient in DNA polymerase beta die perinatally, we studied the effects of DNA polymerase beta deficiency in mosaic animals. We found that some of the mosaic polymerase beta-deficient animals were viable, but were often reduced in size and weight. The fraction of DNA polymerase beta-deficient cells in mosaic embryos decreased during embryonic development, presumably because wild-type cells had a competitive advantage. The nestin-cre transgenic mice can be used to generate mosaic animals in which target genes are mutated by Cre-mediated recombination of loxP-flanked target genes. By using mosaic animals, embryonic lethality can be bypassed and cell lineages for whose development a given target gene is critical can be identified. In the case of DNA polymerase beta, deficient cells are already

Lethal midline granuloma histologically. Management with radiation therapy

International Nuclear Information System (INIS)

Barriga T, L.; Misad, O.; Moscol, A.; Pinillos G, L.; Barriga T, O.; Heredia, A.; Pinillos A, L.; Mayer Z, T.

1995-01-01

From 1973 through 1990, 24 patients with lethal midline granuloma histologically demonstrated were treated with radiation therapy at the Radiation Oncology Department of the National Institute of Neoplasmic Diseases from Peru. The authors reports the results of their experience, reviewed the literature and present a clinic and pathologic discussion of this rare entity. All the patients received radiotherapy as the main treatment and 12 of them received chemotherapy. The male to female ratio was 5:3 with a mean age of 29.33 years (range 6 to 84 years old). Symptoms of nasal obstruction were presented 45.83%, nasal enlargement in 33.33%, nasal discharge in 29.16% and fever in 29.16%, principally. We believe that radiotherapy is the treatment of choice in this report we can not demonstrate it because of the small number of patients. (authors). 28 refs., 10 tabs

The lethality test used for estimating the potency of antivenoms against Bothrops asper snake venom: pathophysiological mechanisms, prophylactic analgesia, and a surrogate in vitro assay.

Science.gov (United States)

Chacón, Francisco; Oviedo, Andrea; Escalante, Teresa; Solano, Gabriela; Rucavado, Alexandra; Gutiérrez, José María

2015-01-01

The potency of antivenoms is assessed by analyzing the neutralization of venom-induced lethality, and is expressed as the Median Effective Dose (ED50). The present study was designed to investigate the pathophysiological mechanisms responsible for lethality induced by the venom of Bothrops asper, in the experimental conditions used for the evaluation of the neutralizing potency of antivenoms. Mice injected with 4 LD50s of venom by the intraperitoneal route died within ∼25 min with drastic alterations in the abdominal organs, characterized by hemorrhage, increment in plasma extravasation, and hemoconcentration, thus leading to hypovolemia and cardiovascular collapse. Snake venom metalloproteinases (SVMPs) play a predominat role in lethality, as judged by partial inhibition by the chelating agent CaNa2EDTA. When venom was mixed with antivenom, there was a venom/antivenom ratio at which hemorrhage was significantly reduced, but mice died at later time intervals with evident hemoconcentration, indicating that other components in addition to SVMPs also contribute to plasma extravasation and lethality. Pretreatment with the analgesic tramadol did not affect the outcome of the neutralization test, thus suggesting that prophylactic (precautionary) analgesia can be introduced in this assay. Neutralization of lethality in mice correlated with neutralization of in vitro coagulant activity in human plasma. Copyright © 2014 Elsevier Ltd. All rights reserved.

Loss of ATM kinase activity leads to embryonic lethality in mice

DEFF Research Database (Denmark)

Daniel, J.A.; Pellegrini, M.; Filsuf, D.

2012-01-01

whether the functions of ATM are mediated solely by its kinase activity, we generated two mouse models containing single, catalytically inactivating point mutations in Atm. In this paper, we show that, in contrast to Atm-null mice, both D2899A and Q2740P mutations cause early embryonic lethality in mice......, without displaying dominant-negative interfering activity. Using conditional deletion, we find that the D2899A mutation in adult mice behaves largely similar to Atm-null cells but shows greater deficiency in homologous recombination (HR) as measured by hypersensitivity to poly (adenosine diphosphate...

Characterization of conditionally expressed mutants affecting age-specific Drosophila melanogaster : Lethal conditions and temperature-sensitive periods

NARCIS (Netherlands)

Vermeulen, CJ; Bijlsma, R

The specific genetic basis of inbreeding depression is poorly understood. To address this question, two conditionally expressed lethal effects that were found to cause line-specific life span reductions in two separate inbred lines of Drosophila melanogaster. were characterized phenotypically and