Enzymatic biomarkers as indicators of dietary cadmium in gypsy moth caterpillars.

PubMed

Vlahović, Milena; Mataruga, Vesna Perić; Mrdaković, Marija; Matić, Dragana; Lazarević, Jelica; Nenadović, Vera; Ilijin, Larisa

2013-05-01

Heavy metals damage the structure, chemistry, and function of cells, including enzyme systems inside them. Variation in the profile of biochemical biomarkers in prevalent species should be used for assessing environmental contamination. The present study pays attention to the phosphatases present in the midgut of gypsy moth fourth instar caterpillars, which had been exposed to short- and long-term cadmium intake at 10 and 30 μg Cd/g dry food. Chronic cadmium ingestion significantly inhibited the activity of all examined phosphatases, while only the activity of lysosomal phosphatase was acutely decreased. Total acid phosphatase activity recovered from both long-term cadmium treatments within 3 days. The low index of phenotypic plasticity was connected to high variability of plasticity. Dependence of phosphatase isoforms on genotype and duration of cadmium treatment was determined. We concluded that, with further investigations, profiling of total acid phosphatase activity, as well as the lysosomal fraction can be used as a biomarker for acute sublethal metal toxicity.

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).

PubMed

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 (< 2 h) locomotor hyperactivity followed by a long-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.

Lethal and sublethal effects of aniline and chlorinated anilines on zebrafish embryos and larvae.

PubMed

Horie, Yoshifumi; Yamagishi, Takahiro; Koshio, Masaaki; Iguchi, Taisen; Tatarazako, Norihisa

2017-07-01

Environmental risk assessments show increased attention to the sublethal effects of chemicals on aquatic organisms. The Organization for Economic Cooperation and Development (OECD) established the "Fish, Short-term Toxicity Test on Embryo and Sac-fry Stages" (OECD test 212) to predict lethal effects. It is still unclear, however, whether this test can predict sublethal effects. Although their sublethal effects are still unknown, chlorinated anilines are widely used in various fields. The purpose of this study, therefore, is to investigate sublethal effects of chlorinated anilines using OECD test 212 with zebrafish, and to examine the correlation of several sublethal effects between embryo and larval stages. Embryos were exposed to aniline and nine chlorinated anilines until 8 days post-fertilization. A delayed lethal effect was observed from three of the 10 anilines tested. In the control group, the swim bladder inflated after hatching, but there was no swim-bladder inflation after exposure to the chlorinated anilines. Fertilized eggs exposed to lower concentrations of test chemicals showed effects during embryogenesis that did not affect mortality rates, such as changes in body curvature and edema. Our results show that chlorinated anilines induce not only lethal effects but also a variety of sublethal effects. Moreover, a detailed estimate of these effects requires study during both embryonic and larval stages. OECD test 212 may therefore prove useful as a method for screening chemicals for lethal and sublethal effects. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Kinetic analysis of the swimming behavior of the goldfish, Carassius auratus, exposed to nickel: Hypoactivity induced by sublethal concentrations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ellgaard, E.G.; Ashley, S.E.; Langford, A.E.

1995-12-01

The discharge of nickel into aquatic environments from numerous industries poses a threat to fish populations because of its toxcity. Although little is known, however, about the precise mechanism of its toxicity in freshwater fish, it produces some of the symptoms associated with heavy-metal poisoning in general; it accumulates in fish tissues and results in alterations in gill structure, including hypertrophy of respiratory and mucous cells, separation of the epithelial layer from the pillar cell system, cauterization and sloughing, and necrosis of the epithelium. The destruction of the gill lamellae decreases the ventilation rate and if severe, as after acutemore » exposure, may cause blood hypoxia and death. The effects of short-term exposure of fish to sublethal concentrations of nickel and not as well defined. The kinetic method of Ellgaard et al., which uses locomotor activity to assess the general health of fish, is ideally suited to examine whether sublethal concentrations of nickel adversely affect fish. In previous studies, the measured changes in locomotor activity observed when fish are exposed to pollutants correlate with more specific changes, e.g., physiological, biochemical, histological or neurosensory changes, which occur under the same conditions. Thus, the kinetic method also meets the criterial for pollution early warning systems as discussed by Cairns and van der Schale. This method has previously been used to demonstrate that short-term exposure to sublethal concentrations of the heavy metals cadmium, chromium, and zinc and copper are detrimental to the health of bluegills. The present study examines the effects of short-term exposures of sublethal concentrations of nickel on the locomotor activity of the goldfish, Carassius auratus. 11 refs., 1 fig., 2 tabs.« less

Zinc oxide nanoparticles and monocytes: Impact of size, charge and solubility on activation status

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prach, Morag; Stone, Vicki; Proudfoot, Lorna, E-mail: l.proudfoot@napier.ac.uk

2013-01-01

Zinc oxide (ZnO) particle induced cytotoxicity was dependent on size, charge and solubility, factors which at sublethal concentrations may influence the activation of the human monocytic cell line THP1. ZnO nanoparticles (NP; average diameter 70 nm) were more toxic than the bulk form (< 44 μm mesh) and a positive charge enhanced cytotoxicity of the NP despite their relatively high dissolution. A positive charge of the particles has been shown in other studies to have an influence on cell viability. Centrifugal filtration using a cut off of 5 kDa and Zn element analysis by atomic absorption spectroscopy confirmed that exposuremore » of the ZnO particles and NP to 10% foetal bovine serum resulted in a strong association of the Zn{sup 2+} ion with protein. This association with protein may influence interaction of the ZnO particles and NP with THP1 cells. After 24 h exposure to the ZnO particles and NP at sublethal concentrations there was little effect on immunological markers of inflammation such as HLA DR and CD14, although they may induce a modest increase in the adhesion molecule CD11b. The cytokine TNFα is normally associated with proinflammatory immune responses but was not induced by the ZnO particles and NP. There was also no effect on LPS stimulated TNFα production. These results suggest that ZnO particles and NP do not have a classical proinflammatory effect on THP1 cells. -- Highlights: ► ZnO is cytotoxic to THP-1 monocytes. ► ZnO nanoparticles are more toxic than the bulk form. ► Positive charge enhances ZnO nanoparticle cytotoxicity. ► Sublethal doses of ZnO particles do not induce classical proinflammatory markers.« less

Pre-treatment of Stegomyia aegypti mosquitoes with a sublethal dose of imidacloprid impairs behavioural avoidance induced by lemon oil and DEET.

PubMed

Thany, S H; Tong, F; Bloomquist, J R

2015-03-01

The present study was conducted to determine whether imidacloprid can impair the avoidance behaviour of the mosquito Stegomyia aegypti. Laboratory investigations using a T-maze apparatus showed that St. aegypti mosquitoes present long term avoidance behaviour when they are exposed to repetitive trials with lemon oil and DEET. The present study tested the effect of a sublethal dose of imidacloprid on the avoidance behaviour of St. aegypti mosquitoes over a 48 h period. Data suggest that 0.5 ng of imidacloprid/mosquito reduces the avoidance behaviour of mosquitoes exposed to lemon oil, on the first day of exposure, after the second trial; whereas imidacloprid affected DEET repellency only the first day of exposure, after the second trial. Imidacloprid was toxic against St. aegypti mosquitoes, and at sublethal doses was able to impair the repellency induced by lemon oil and DEET. The present data were consistent with the finding that St. aegypti mosquitoes exhibit long term avoidance behaviour, and treatment of mosquitoes with a sublethal dose of imidacloprid under DEET application can affect the repellency of DEET against St. aegypti. © 2014 The Royal Entomological Society.

Demonstration of an adaptive response to preconditioning Frankliniella occidentalis (Pergande) to sublethal doses of spinosad: a hormetic-dose response.

PubMed

Gong, Youhui; Xu, Baoyun; Zhang, Youjun; Gao, Xiwu; Wu, Qingjun

2015-07-01

Sublethal doses of some insecticides have been reported to either stimulate or reduce the survival and fecundity of insects. Many sublethal-effect studies have been conducted after exposure of only one generation to sublethal insecticides, and there is little information about the sublethal effects on insects after long-term exposure to sublethal insecticides. In this study, changes in biological characteristics were investigated in spinosad-susceptible (Spin-S) and sublethal-spinosad-treated (Spin-Sub) strains of Frankliniella occidentalis (Pergande) after exposure to their corresponding sublethal concentrations of spinosad. The results showed that for the Spin-S strain, the LC10 concentration of spinosad slightly affected the biotic fitness both in parents and offspring of F. occidentalis. The LC25 concentration of spinosad prolonged the development time, reduced the fecundity, and significantly reduced the intrinsic rate of increase, the net reproductive rate and the finite rate of increase in the Spin-S strain. However, the negative effects were not as pronounced in the offspring (F1 generation) as in the parent generation. For the Spin-Sub strain, the LC10 and LC25 concentrations of spinosad had little negative effect on the development and fecundity, and no significant difference was found between the effects of the LC10 and LC25 treatments on the Spin-Sub strain. The Spin-Sub strain exhibited a shorter developmental time, and larger intrinsic rates of increase and net reproductive rates, compared with the corresponding treatments of the Spin-S strain. These findings combined with our previous studies suggest that the biotic fitness increased in the Spin-Sub strain and the strain became more adaptable to sublethal doses of spinosad, compared with the Spin-S strain. Physiological and biochemical adaptation may contribute to these changes after long treatment times at sublethal doses.

Use of chironomids (Diptera: Chironomidae) as bioindicators of contaminant stress: Biochemical, chromosomal and developmental measures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ciborowski, J.J.H.; Cervi, L.; Sinasac, D.

1995-12-31

Sublethal environmental stresses produce effects ranging from subtle biochemical changes that protect an organism from damage, through developmental effects that interfere with growth and compromise fitness. Benthic chironomids live in intimate contact with the sediments to which most persistent chemicals are bound. Their short life cycle and unique developmental and genetic structure make them excellent candidates as biological indicators of stress. The authors evaluated the short and long-term responses of Chironomus riparius larvae to contaminants. To determine short-term stress responses, third and fourth instar Chironomus larvae were exposed to up to 1.5 {micro}L/g creosote or up to 100 {micro}g/g Cdmore » for 12 h. Creosote-exposed larvae exhibited proteins of a molecular weight consistent with production of heat shock proteins of the HSP 70 family. Exposure to Cd induced significant enlargement of Balbiani Rings of the 4th chromosome in chironomid salivary glands, indicative of increased transcription of RNA precursors to salivary mucoproteins. Chironomus larvae individually reared from second instar larvae at [Cd] up to 40 {micro}g/g sediment exhibited increased incidence of mentum deformities, and delayed development that resulted in larger size at pupation. Thus deformities are biologically relevant indicators of stress. Overall, the results confirm the potential of chironomids as relevant bioindicators of contaminant stress.« less

Effect of single and binary combinations of plant-derived molluscicides on different enzyme activities in the nervous tissue of Achatina fulica.

PubMed

Rao, I G; Singh, Amrita; Singh, V K; Singh, D K

2003-01-01

Effect of single and binary treatments of plant-derived molluscicides on different enzymes--acetylcholinesterase (AChE), lactic dehydrogenase (LDH) and acid/alkaline phosphatase (ACP/ALP)--in the nervous tissue of the harmful terrestrial snail Achatina fulica were studied. Sublethal in vivo 24-h exposure to 40% and 80% LC(50) of Azadirachta indica oil, Cedrus deodara oil, Allium sativum bulb powder, Nerium indicum bark powder and binary combinations of A. sativum (AS) + C. deodara (CD) and CD + A. indica (AI) oils significantly altered the activity of these enzymes in the nervous tissue of Achatina fulica. The binary treatment of AS + CD was more effective against AChE, LDH, and ALP than the single ones. However, binary treatment of AI + CD was more effective against ALP. Copyright 2003 John Wiley & Sons, Ltd.

Survey and evaluation of contaminants in earthworms and in soils derived from dredged material at confined disposal facilities in the Great Lakes region

USGS Publications Warehouse

Beyer, W.N.; Stafford, C.

1993-01-01

Soils derived from dredged material were collected, together with earthworms from nine confined disposal facilities located in the Great Lakes Region. These samples were analyzed for 18 elements, 11 organochlorine pesticides, PCBs, and 24 polycyclic aromatic hydrocarbons. The concentrations detected in earthworms were evaluated in terms of their potential hazard to wildlife, which for the sake of the evaluation were assumed to prey entirely either on earthworms or on other soil invertebrates having similar concentrations. The soil concentrations (dry wt.) of the contaminants of greatest concern were < 1.9 to 32 ppm Cd, < 0.053 to 0.94 ppm Hg, 4.6 to 550 ppm Pb, and < 0.1 to 1.0 ppm PCBs. The concentrations in earthworms (dry wt., ingested soil included) were as high as 91 ppm Cd, 1.6 ppm Hg, 200 ppm Pb, and 1.8 ppm PCBs. Based on laboratory toxicity studies of relatively sensitive species, and on concentration factors calculated from the earthworm and soil data, we estimated that lethal or serious sublethal effects on wildlife might be expected at concentrations of 10 ppm Cd, 3 ppm Hg, 670 ppm Pb, and 1.7 ppm PCBs in alkaline surface soils derived from dredged material. Concentrations of polycyclic aromatic hydrocarbons in earthworms were well below those in soil.

Cadmium neurotoxicity to a freshwater planarian.

PubMed

Wu, Jui-Pin; Lee, Hui-Ling; Li, Mei-Hui

2014-11-01

Although freshwater planarians are evolutionarily primitive, they are some of the simplest bilateral animals possessing integrated neural networks similar to those in vertebrates. We attempted to develop planarian Dugesia japonica as a model for investigating the neurotoxicity of environmental pollutants such as cadmium (Cd). This study was therefore designed to study the effects of Cd on the locomotor activity, neurobehavior, and neurological enzymes of D. japonica. After planarians were exposed to Cd at high concentrations, altered neurobehavior was observed that exhibited concentration-dependent patterns. Morphological alterations in Cd-treated planarians included irregular shape, body elongation, screw-like hyperkinesia, and bridge-like position. To study the direct effects of Cd on neurological enzymes, tissue homogenates of planarians were incubated in vitro with Cd before their activity was measured. Results showed that acetylcholinesterase (AChE), adenosine triphosphatase (ATPase), and monoamine oxidase A (MAO-A) activities were inhibited in a concentration-dependent manner. MAO-B activity was significantly induced by Cd at low concentrations and inhibited at high concentrations. Changes in the in vivo activity of AChE and ATPase were also found after planarians were treated with Cd at a sublethal concentration (5.56 μM). These observations indicate that neurotransmission systems in planarians are disturbed after Cd exposure.

Sublethal Growth Effects and Mortality to Marine Bivalves and Fish from Long-Term Exposure to Tributyltin.

DTIC Science & Technology

1985-07-01

sublethal toxicity of tributyltin oxide (TBTO) and its putative environmental product, tribu- tyltin sulfide ( TBTS ) to zoeal mud crabs, RIthropanopeus...EXPOSURE TO TRIBUTYLTIN A. Valkirs . B. Davidson Computer Sciences Corporation P. Seligman Naval Ocean Systems Center -5 . - - Naval Ocean Systems...Organotin .,’vwfuf coatingsu~~ study better defines the longterm toxicity and bloaccumnulation potential of tributyltin released from antifouting

Do Biopesticides Affect the Demographic Traits of a Parasitoid Wasp and Its Biocontrol Services through Sublethal Effects?

PubMed Central

Biondi, Antonio; Zappalà, Lucia; Stark, John D.; Desneux, Nicolas

2013-01-01

Pesticide risk assessments are usually based on short-term acute toxicity tests, while longer-term population dynamic related traits, critical to the success of biological control and Integrated Pest Management (IPM) programs, are often overlooked. This is increasingly important with respect to new biopesticides that frequently cause no short-term acute effects, but that can induce multiple physiological and behavioral sublethal effects, leading to a decrease in population growth and ecosystem services. In this study we assessed the lethal and sublethal effects of six biopesticides [abamectin, azadirachtin, Bacillus thuringiensis, borax plus citrus oil (Prev-Am®), emamectin benzoate, and spinosad], used in tomato crops to control the invasive pest Tuta absoluta (Lepidoptera: Gelechiidae), on adults and pupae of the parasitoid Bracon nigricans (Hymenoptera: Braconidae). Data on female survival and production of female offspring were used to calculate population growth indexes as a measure of population recovery after pesticide exposure. Spinosad caused 100% and 80% mortality in exposed adults (even 10 d after the treatment) and pupae, respectively. Although most of the biopesticides had low levels of acute toxicity, multiple sublethal effects were observed. The biocontrol activity of both females that survived 1-h and 10-d old residues, and females that emerged from topically treated pupae was significantly affected by the application of the neurotoxic insecticides emamectin benzoate and abamectin. Furthermore, very low B. nigricans demographic growth indices were estimated for these two insecticides, indicating potential local extinction of the wasp populations. Among the tested products, Bt proved to be the safest for B. nigricans adults and pupae. Our findings emphasize that acute toxicity assessment alone cannot fully predict the actual impact of pesticides on non-target parasitoids. Thus, sublethal effects related to the species specific life-history variables must be carefully considered in order to assess pesticide risks and to incorporate new pesticides, including biopesticides, into IPM programmes. PMID:24098793

Chronic Sublethal Effects of San Francisco Bay Sediments on Nereis (Neanthes) arenaceodentata; Full Life-Cycle Exposure to Bedded Sediments

DTIC Science & Technology

1993-06-01

COMMUNITY ENZYME OSMOREGULATION ENERGY FLOW DNA/RNA BEHAVIOR NUTRIENT CYCLING END POINT MEMBRANES METABOLISM INTRASPECIFIC HISTOPATHOLOGY SURVIVAL...Miscellaneous Paper D-93-2AD-A268 207 June 1993 US Army Corps of Engineers Waterways Experiment Station Long-Term Effects of Dredging Operations...Program Chronic Sublethal Effects of San Francisco Bay Sediments on Nereis (Neanthes) arenaceodentata; Full Life-Cycle Exposure to Bedded Sediments by

Metallothionein as potential biomarker of cadmium exposure in Persian sturgeon (Acipenser persicus).

PubMed

Shariati, Fatemeh; Esaili Sari, Abbas; Mashinchian, Ali; Pourkazemi, Mohammad

2011-10-01

Metallothionein (MT) concentration in gills, liver, and kidney tissues of Persian sturgeon (Acipenser persicus) were determined following exposure to sublethal levels of waterborne cadmium (Cd) (50, 400, and 1,000 μg l(-1)) after 1, 2, 4, and 14 days. The increases of MT from background levels were 4.6-, 3-, and 2.8-fold for kidney, liver, and gills, respectively. The results showed that MT level change in the kidney is time and concentration dependent. Also, cortisol measurement revealed elevation at the day 1 of exposure and followed by MT increase in the liver. Cd concentrations in the cytosol of experimental tissues were measured, and the results indicated that Cd levels in the cytosol of liver, kidney, and gills increased 240.71-, 32.05-, and 40.16-fold, respectively, 14 days after exposure to 1,000 μg l(-1) Cd. The accumulation of Cd in cytosol of tissues is in the order of liver > gills > kidney. Pearson correlation coefficients showed that the MT content in kidney is correlated with Cd concentration, the value of which is more than in liver and gills. Thus, kidney can be considered as a tissue indicator in A. persicus for waterborne Cd contamination.

Chronic Sublethal Effects of San Francisco Bay Sediments on Nereis (Neanthes) arenaceodentata; Effect of Food Ration on Sediment Toxicity

DTIC Science & Technology

1993-09-01

developing oocytes. In effect , gametogenesis and subsequent reproductive success are largely dependent on the energy and metabolic substrates assimi- lated...Miscellaneous Paper D-93-4 September 1993 US Army Corps AD-A269 901 of Engineers Waterways Experiment i Ii Station Long- Term Effects of Dredging...Operations Program Chronic Sublethal Effects of San Francisco Bay Sediments on Nereis (Neanthes) arenaceodentata; Effect of Food Ration on Sediment

Daoy medulloblastoma cells that express CD133 are radioresistant relative to CD133- cells, and the CD133+ sector is enlarged by hypoxia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blazek, Ed R.; Foutch, Jennifer L.; Maki, Guitta

2007-01-01

Purpose: Primary medulloblastoma and glioblastoma multiforme tumor cells that express the surface marker CD133 are believed to be enriched for brain tumor stem cells because of their unique ability to initiate or reconstitute tumors in immunodeficient mice. This study sought to characterize the radiobiological properties and marker expression changes of CD133+ vs. CD133- cells of an established medulloblastoma cell line. Methods and Materials: Daoy and D283 Med cell lines were stained with fluorescently labeled anti-CD133 antibody and sorted into CD133+ and CD133- populations. The effect of oxygen (2% vs. 20%) on CD133 expression was measured. Both populations were analyzed formore » marker stability, cell cycle distribution, and radiosensitivity. Results: CD133+ Daoy cells restored nearly native CD133+ and CD133- populations within 18 days, whereas CD133- cells remained overwhelmingly CD133-. Culturing Daoy cells in 2% oxygen rather than the standard 20% oxygen increased their CD133 expression 1.6-fold. CD133+ Daoy cells were radioresistant via the {beta}-parameter of the linear-quadratic model relative to CD133- Daoy cells, although their {alpha}-parameters and cell cycle distributions were identical. Conclusions: Restoration of the original CD133+ and CD133- populations from CD133+ Daoy cells in serum is further evidence that CD133+ cells are functionally distinct from CD133- cells. The radioresistance of CD133+ compared with CD133- Daoy cells is consistent with better repair of sublethal damage. Enlargement of the CD133+ sector is a new feature of the hypoxic response.« less

Failure in generating hemopoietic stem cells is the primary cause of death from cytomegalovirus disease in the immunocompromised host

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mutter, W.; Reddehase, M.J.; Busch, F.W.

1988-05-01

We have shown in a murine model system for cytomegalovirus (CMV) disease in the immunocompromised host that CMV infection interferes with the earliest detectable step in hemopoiesis, the generation of the stem cell CFU-S-I, and thereby prevents the autoreconstitution of bone marrow after sublethal irradiation. The antihemopoietic effect could not be ascribed to a direct infection of stem cells. The failure in hemopoiesis was prevented by adoptive transfer of antiviral CD8+ T lymphocytes and could be overcome by syngeneic bone marrow transplantation. CD8+ T lymphocytes and bone marrow cells both mediated survival, although only CD8+ T lymphocytes were able tomore » limit virus multiplication in host tissues. We concluded that not the cytopathic effect of virus replication in host tissues, but the failure in hemopoiesis, is the primary cause of death in murine CMV disease.« less

Chronic Sublethal Effects of San Francisco Bay Sediments on Nereis (Neanthes) arenaceodentata; Interpretative Guidance for a Growth End Point

DTIC Science & Technology

1993-09-01

carbohydrates from the worm’s internal musculature and transfer them to developing oocytes. In effect , the energy and metabolic 22 Chapter 4 Discussion...Miscellaneous Paper D-93-5 September 1993 US Army Corps AD-A269 836 of Engineers Waterways Experiment IIii l llli, Station Long- Term Effects of...Dredging Operations Program Chronic Sublethal Effects of San Francisco Bay Sediments on Nereis (Neanthes) arenaceodentata; Interpretative Guidance for a

Sub-lethal radiation enhances anti-tumor immunotherapy in a transgenic mouse model of pancreatic cancer

PubMed Central

Cao, Zhu Alexander; Daniel, Dylan; Hanahan, Douglas

2002-01-01

Background It is not uncommon to observe circulating tumor antigen-specific T lymphocytes in cancer patients despite a lack of significant infiltration and destruction of their tumors. Thus, an important goal for tumor immunotherapy is to identify ways to modulate in vivo anti-tumor immunity to achieve clinical efficacy. We investigate this proposition in a spontaneous mouse tumor model, Rip1-Tag2. Methods Experimental therapies were carried out in two distinctive trial designs, intended to either intervene in the explosive growth of small tumors, or regress bulky end-stage tumors. Rip1-Tag2 mice received a single transfer of splenocytes from Tag-specific, CD4+ T cell receptor transgenic mice, a single sub-lethal radiation, or a combination therapy in which the lymphocyte transfer was preceded by the sub-lethal radiation. Tumor burden, the extent of lymphocyte infiltration into solid tumors and host survival were used to assess the efficacy of these therapeutic approaches. Results In either intervention or regression, the transfer of Tag-specific T cells alone did not result in significant lymphocyte infiltration into solid tumors, not did it affect tumor growth or host survival. In contrast, the combination therapy resulted in significant reduction in tumor burden, increase in lymphocyte infiltration into solid tumors, and extension of survival. Conclusions The results indicate that certain types of solid tumors may be intrinsically resistant to infiltration and destruction by tumor-specific T lymphocytes. Our data suggest that such resistance can be disrupted by sub-lethal radiation. The combinatorial approach presented here merits consideration in the design of clinical trials aimed to achieve T cell-mediated anti-tumor immunity. PMID:12019035

Sublethal doses of neonicotinoid imidacloprid can interact with honey bee chemosensory protein 1 (CSP1) and inhibit its function.

PubMed

Li, Hongliang; Tan, Jing; Song, Xinmi; Wu, Fan; Tang, Mingzhu; Hua, Qiyun; Zheng, Huoqing; Hu, Fuliang

2017-04-29

As a frequently used neonicotinoid insecticide, imidacloprid can impair the chemoreceptive behavior of honey bees even at sublethal doses, while the physiochemical mechanism has not been further revealed. Here, multiple fluorescence spectra, thermodynamic method, and molecular docking were used to study the interaction and the functional inhibition of imidacloprid to the recombinant CSP1 protein in Asian honey bee, Apis cerana. The results showed that the fluorescence intensity (λ em  = 332 nm) of CSP1 could be significantly quenched by imidacloprid in a dynamic mode. During the quenching process, ΔH > 0, ΔS > 0, indicating that the acting forces of imidacloprid with CSP1 are mainly hydrophobic interactions. Synchronous fluorescence showed that the fluorescence of CSP1 was mainly derived from tryptophan, and the hydrophobicity of tryptophan decreased with the increase of imidacloprid concentration. Molecular docking predicted the optimal pose and the amino acid composition of the binding process. Circular dichroism (CD) spectra showed that imidacloprid reduced the α-helix of CSP1 and caused the extension of the CSP1 peptide chain. In addition, the binding of CSP1 to floral scent β-ionone was inhibited by nearly 50% of the apparent association constant (K A ) in the presence of 0.28-2.53 ng/bee of imidacloprid, and the inhibition rate of nearly 95% at 3.75 ng/bee of imidacloprid at sublethal dose level. This study initially revealed the molecular physiochemical mechanism that sublethal doses of neonicotinoid still interact and inhibit the physiological function of the honey bees' chemoreceptive system. Copyright © 2017 Elsevier Inc. All rights reserved.

Acute exposure to selenium disrupts associative conditioning and long-term memory recall in honey bees (Apis mellifera).

PubMed

Burden, Christina M; Elmore, Christopher; Hladun, Kristen R; Trumble, John T; Smith, Brian H

2016-05-01

A plethora of toxic compounds - including pesticides, heavy metals, and metalloids - have been detected in honey bees (Apis mellifera) and their colonies. One such compound is selenium, which bees are exposed to by consuming nectar and pollen from flowers grown in contaminated areas. Though selenium is lethal at high concentrations, sublethal exposure may also impair honey bees' ability to function normally. Examining the effect of selenium exposure on learning and memory provides a sensitive assay with which to identify sublethal effects on honey bee health and behavior. To determine whether sublethal selenium exposure causes learning and memory deficits, we used proboscis extension reflex conditioning coupled with recall tests 30min and 24h post-conditioning. We exposed forager honey bees to a single sublethal dose of selenium, and 3h later we used an olfactory conditioning assay to train the bees to discriminate between one odor associated with sucrose-reinforcement and a second unreinforced odor. Following conditioning we tested short- and long-term recall of the task. Acute exposure to as little as 1.8ng of an inorganic form of selenium (sodium selenate) before conditioning caused a reduction in behavioral performance during conditioning. And, exposure to 18ng of either an inorganic form (sodium selenate) or an organic form (methylseleno-l-cysteine) of selenium caused a reduction in the bees' performance during the long-term recall test. These concentrations of selenium are lower than those found in the nectar of plants grown in selenium-contaminated soil, indicating that even low-grade selenium toxicity produces significant learning and memory impairments. This may reduce foragers' ability to effectively gather resources for the colony or nurse bees' ability to care for and maintain a healthy colony. Copyright © 2016. Published by Elsevier Inc.

Effects of tributyltin and benzo[a]pyrene on the immune-associated activities of hemocytes and recovery responses in the gastropod abalone, Haliotis diversicolor.

PubMed

Gopalakrishnan, Singaram; Huang, Wei-Bin; Wang, Qiang-Wei; Wu, Man-Li; Liu, Jie; Wang, Ke-Jian

2011-08-01

Our previous study reports that short-term exposure to sublethal concentrations of benzo[a]pyrene (BaP) induces immunomodulation in the gastropod abalone, Haliotis diversicolor. In the present study, it was further observed that long-term chronic exposure to sublethal concentrations of BaP modulated the immunocompetence of abalones in terms of the change in activity of the antioxidant and immune associated parameters tested. In addition, the effect of tributyltin (TBT), another important genotoxicant in the aquatic environment, was investigated. Exposure of abalones to sublethal concentrations of TBT and BaP for 21 days resulted in significant decrease of total hemocyte count, phagocytosis, membrane stability and lysozyme activity. Conversely induction of extra and intra cellular superoxide generation, nitric oxide, nitric oxide synthase and myeloperoxidase activity was present when the abalones were exposed to TBT and BaP. Most of the immune associated parameters tested showed clear time dependent response to both toxicants. Within 14 days after the 21 day exposure to BaP, recovery was observed as evidenced by most of the parameters returning to their normal level. However, no recovery was observed within 14 days after the 21 day exposure to TBT as evidenced by continued elevation of intra cellular superoxide and nitrite production and decrease in THC, membrane stability and lysozyme activity. This suggested a prolonged TBT-induced impact on the immune reaction and possibly more damage than that caused by BaP. Overall the results suggest that chronic exposure to sublethal concentrations of TBT or BaP causes modulations in the immunocompetence of abalones with most of the immune associated parameters tested being stimulated, and this might be harmful to the host. Copyright © 2011 Elsevier Inc. All rights reserved.

Mast cells in Waldenstrom's macroglobulinemia support lymphoplasmacytic cell growth through CD154/CD40 signaling.

PubMed

Tournilhac, O; Santos, D D; Xu, L; Kutok, J; Tai, Y-T; Le Gouill, S; Catley, L; Hunter, Z; Branagan, A R; Boyce, J A; Munshi, N; Anderson, K C; Treon, S P

2006-08-01

Bone marrow (BM) mast cells (MC) are commonly found in association with lymphoplasmacytic cells (LPC) in patients with Waldenström's macroglobulinemia (WM). We therefore sought to clarify the role of MC in WM. Co-culture of sublethally irradiated HMC-1 MC, KU812 basophilic cells, or autologous BM MC along with BM LPC from WM patients resulted in MC dose-dependent tumor colony formation and/or proliferation as assessed by 3H-thymidine uptake studies. Furthermore, by immunohistochemistry, multicolor flow cytometry and/or RT-PCR analysis, CD40 ligand (CD154), a potent inducer of B-cell expansion, was expressed on BM MC from 32 of 34 (94%), 11 of 13 (85%), and 7 of 9 (78%) patients, respectively. In contrast, MC from five healthy donors did not express CD154. By multicolor flow cytometry, CD154 was expressed on BM LPC from 35 of 38 (92%) patients and functionality was confirmed by CD154 and CD40 agonistic antibody stimulation, which induced proliferation, support survival and/or pERK phosphorylation of LPC. Moreover, MC induced expansion of LPC from 3 of 5 patients was blocked in a dose dependent manner by use of a CD154 blocking protein. These studies demonstrate that in WM, MC may support tumor cell expansion through constitutive CD154-CD40 signaling and therefore provide the framework for therapeutic targeting of MC and MC-WM cell interactions in WM.

Development of Cardiovascular and Neurodevelopmental Metrics as Sublethal Endpoints for the Fish Embryo Toxicity Test.

PubMed

Krzykwa, Julie C; Olivas, Alexis; Jeffries, Marlo K Sellin

2018-06-19

The fathead minnow fish embryo toxicity (FET) test has been proposed as a more humane alternative to current toxicity testing methods, as younger organisms are thought to experience less distress during toxicant exposure. However, the FET test protocol does not include endpoints that allow for the prediction of sublethal adverse outcomes, limiting its utility relative to other test types. Researchers have proposed the development of sublethal endpoints for the FET test to increase its utility. The present study 1) developed methods for previously unmeasured sublethal metrics in fathead minnows (i.e., spontaneous contraction frequency and heart rate) and 2) investigated the responsiveness of several sublethal endpoints related to growth (wet weight, length, and growth-related gene expression), neurodevelopment (spontaneous contraction frequency, and neurodevelopmental gene expression), and cardiovascular function and development (pericardial area, eye size and cardiovascular related gene expression) as additional FET test metrics using the model toxicant 3,4-dichloroaniline. Of the growth, neurological and cardiovascular endpoints measured, length, eye size and pericardial area were found to more responsive than the other endpoints, respectively. Future studies linking alterations in these endpoints to longer-term adverse impacts are needed to fully evaluate the predictive power of these metrics in chemical and whole effluent toxicity testing. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Simulated response and effects to oil exposure in an estuarine fish species

EPA Science Inventory

Experimental toxicity data alone lack ecological relevance to assess more realistic situations, such as variable exposure to a contaminant and long-term impact. Evaluating the implications of sublethal effects or behavioral response to exposure requires long-term, population-leve...

A stromal cell free culture system generates mouse pro-T cells that can reconstitute T-cell compartments in vivo.

PubMed

Gehre, Nadine; Nusser, Anja; von Muenchow, Lilly; Tussiwand, Roxane; Engdahl, Corinne; Capoferri, Giuseppina; Bosco, Nabil; Ceredig, Rhodri; Rolink, Antonius G

2015-03-01

T-cell lymphopenia following BM transplantation or diseases such as AIDS result in immunodeficiency. Novel approaches to ameliorate this situation are urgently required. Herein, we describe a novel stromal cell free culture system in which Lineage(-) Sca1(+)c-kit(+) BM hematopoietic progenitors very efficiently differentiate into pro-T cells. This culture system consists of plate-bound Delta-like 4 Notch ligand and the cytokines SCF and IL-7. The pro-T cells developing in these cultures express CD25, CD117, and partially CD44; express cytoplasmic CD3ε; and have their TCRβ locus partially D-J rearranged. They could be expanded for over 3 months and used to reconstitute the T-cell compartments of sublethally irradiated T-cell-deficient CD3ε(-/-) mice or lethally irradiated WT mice. Pro-T cells generated in this system could partially correct the T-cell lymphopenia of pre-Tα(-/-) mice. However, reconstituted CD3ε(-/-) mice suffered from a wasting disease that was prevented by co-injection of purified CD4(+) CD25(high) WT Treg cells. In a T-cell-sufficient or T-lymphopenic setting, the development of disease was not observed. Thus, this in vitro culture system represents a powerful tool to generate large numbers of pro-T cells for transplantation and possibly with clinical applications. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Variations of biomarkers response in mussels Mytilus galloprovincialis to low, moderate and high concentrations of organic chemicals and metals.

PubMed

Perić, Lorena; Nerlović, Vedrana; Žurga, Paula; Žilić, Luka; Ramšak, Andreja

2017-05-01

The changes of acetylcholinesterase activity (AChE), metallothioneins content (MTs), catalase activity (CAT) and lipid peroxidation (LPO) were assessed after 4 days exposure of mussels Mytilus galloprovincialis to a wide range of sublethal concentrations of chlorpyrifos (CHP, 0.03-100 μg/L), benzo(a)pyrene (B(a)P, 0.01-100 μg/L), cadmium (Cd, 0.2-200 μg/L) and copper (Cu, 0.2-100 μg/L). The activity of AChE in the gills decreased after exposure to CHP and Cu, whereas no change of activity was detected after exposure to B(a)P and Cd. Both induction and decrease of MTs content in digestive gland occurred after exposure to CHP and B(a)P, while a marked increase was evident at highest exposure concentrations of Cd. The content of MTs progressively decreased of MTs with increasing concentration of Cu. CAT activity and LPO in the gills did not change after exposure to any of the chemicals. The results demonstrate different response profile in relation to the type of chemical compound, and highlight the potential implications for evaluation of biological effect of contaminants in marine environment. Furthermore, the AChE activity in the gills and MTs content in the digestive gland could be modulated by CHP and Cu at environmentally relevant concentrations indicating the potential risks of short-term transient mussels exposure that may occur due to run-off from land or accidental releases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of the effects of the metals Cd, Cr, Pb and their mixture on the filtration and oxygen consumption rates in catarina scallop, Argopecten ventricosus juveniles.

PubMed

Sobrino-Figueroa, Alma S; Cáceres-Martinez, Carlos

2014-01-01

In this work, we evaluated the effect of sublethal concentrations ( LC25, LC10 and LC5) of cadmium, chromium, lead, and their mixture on the filtration rate and oxygen consumption rate of Catarina scallop, Argopecten ventricosus (Sowerby, 1842), juveniles, in order to evaluate the use of these biomarkers as a reliable tool in environmental monitoring studies, because these metals have been found at high levels in water and sediments in the Mexican Pacific systems. An inverse dose-response relationship was observed when metal concentration and exposure time increased, the filtration rate and oxygen consumption rate reduced. The physiological responses evaluated in this study were sufficiently sensitive to detect alterations in the organisms at 0.014 mg l(-1) Cd, 0.311 mg l(-1) Cr, 0.125 mg l(-1) Pb and 0.05 mg l(-1) Cd + Cr + Pb at 24 and 72 hrs. Cd showed the most drastic effect. The Catarina scallop juveniles were more sensitive to Cd, Cr and Pb as compared to other bivalves. The biomarkers evaluated are a reliable tool to carry out environmental monitoring studies.

Cadmium ion inhibition of quorum signalling in Chromobacterium violaceum.

PubMed

Thornhill, Starla G; Kumar, Manish; Vega, Leticia M; McLean, Robert J C

2017-10-01

Single-celled bacteria are capable of acting as a community by sensing and responding to population density via quorum signalling. Quorum signalling in Chromobacterium violaceum, mediated by the luxI/R homologue, cviI/R, regulates a variety of phenotypes including violacein pigmentation, virulence and biofilm formation. A number of biological and organic molecules have been described as quorum signalling inhibitors but, to date, metal-based inhibitors have not been widely tested. In this study, we show that quorum sensing is inhibited in C. violaceum in the presence of sub-lethal concentrations of cadmium salts. Notable Cd 2+ -inhibition was seen against pigmentation, motility, chitinase production and biofilm formation. Cd-inhibition of quorum-signalling genes occurred at the level of transcription. There was no direct inhibition of chitinase activity by Cd 2+ at the concentrations tested. Addition of the cognate quorum signals, N-hexanoyl homoserine lactone or N-decanoyl homoserine lactone, even at concentrations in excess of physiological levels, did not reverse the inhibition, suggesting that Cd-inhibition of quorum signaling is irreversible. This study represents the first description of heavy metal-based quorum inhibition in C. violaceum.

Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model

PubMed Central

Ishida, Tokiko; Kotani, Hirokazu; Miyao, Masashi; Kawai, Chihiro; Jemail, Leila; Abiru, Hitoshi; Tamaki, Keiji

2016-01-01

The pathogenesis of renal impairment in chronic liver diseases (CLDs) has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy), autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet–fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the pathophysiological mechanisms of sublethal tubular cell injury. PMID:26752420

Human Retinal Transmitochondrial Cybrids with J or H mtDNA Haplogroups Respond Differently to Ultraviolet Radiation: Implications for Retinal Diseases

PubMed Central

Malik, Deepika; Hsu, Tiffany; Falatoonzadeh, Payam; Cáceres-del-Carpio, Javier; Tarek, Mohamed; Chwa, Marilyn; Atilano, Shari R.; Ramirez, Claudio; Nesburn, Anthony B.; Boyer, David S.; Kuppermann, Baruch D.; Jazwinski, S. Michal; Miceli, Michael V.; Wallace, Douglas C.; Udar, Nitin; Kenney, M. Cristina

2014-01-01

Background It has been recognized that cells do not respond equally to ultraviolet (UV) radiation but it is not clear whether this is due to genetic, biochemical or structural differences of the cells. We have a novel cybrid (cytoplasmic hybrids) model that allows us to analyze the contribution of mitochondrial DNA (mtDNA) to cellular response after exposure to sub-lethal dose of UV. mtDNA can be classified into haplogroups as defined by accumulations of specific single nucleotide polymorphisms (SNPs). Recent studies have shown that J haplogroup is high risk for age-related macular degeneration while the H haplogroup is protective. This study investigates gene expression responses in J cybrids versus H cybrids after exposure to sub-lethal doses of UV-radiation. Methodology/Principal Findings Cybrids were created by fusing platelets isolated from subjects with either H (n = 3) or J (n = 3) haplogroups with mitochondria-free (Rho0) ARPE-19 cells. The H and J cybrids were cultured for 24 hours, treated with 10 mJ of UV-radiation and cultured for an additional 120 hours. Untreated and treated cybrids were analyzed for growth rates and gene expression profiles. The UV-treated and untreated J cybrids had higher growth rates compared to H cybrids. Before treatment, J cybrids showed lower expression levels for CFH, CD55, IL-33, TGF-A, EFEMP-1, RARA, BCL2L13 and BBC3. At 120 hours after UV-treatment, the J cybrids had decreased CFH, RARA and BBC3 levels but increased CD55, IL-33 and EFEMP-1 compared to UV-treated H cybrids. Conclusion/Significance In cells with identical nuclei, the cellular response to sub-lethal UV-radiation is mediated in part by the mtDNA haplogroup. This supports the hypothesis that differences in growth rates and expression levels of complement, inflammation and apoptosis genes may result from population-specific, hereditary SNP variations in mtDNA. Therefore, when analyzing UV-induced damage in tissues, the mtDNA haplogroup background may be important to consider. PMID:24919117

Connecting Model Species to Nature: Predator-Induced Long-Term Sensitization in "Aplysia Californica"

ERIC Educational Resources Information Center

Mason, Maria J.; Watkins, Amanda J.; Wakabayashi, Jordann; Buechler, Jennifer; Pepino, Christine; Brown, Michelle; Wright, William G.

2014-01-01

Previous research on sensitization in "Aplysia" was based entirely on unnatural noxious stimuli, usually electric shock, until our laboratory found that a natural noxious stimulus, a single sublethal lobster attack, causes short-term sensitization. We here extend that finding by demonstrating that multiple lobster attacks induce…

Influence of benzoporphyrin-derivative monoacid ring A (BPD-MA, verteporfin) on murine dendritic cells

NASA Astrophysics Data System (ADS)

Hunt, David W. C.; King, Diane E.; Levy, Julia G.

1997-05-01

The impact of bensoporphyrin derivative monoacid ring A, and visible light was determined for mouse splenic dendritic cells (DC), potent antigen-presenting cells (APC) of the immune system. It was discovered that sub-lethal doses of BPD-MA and light significantly altered the surface receptor pattern of DC as well as diminishing the capacity of these cells to activate allogeneic T cells. Treatment of highly purified DC with BPD-MA and 690 nm wavelength light decreased DC expression of major histocompatibility (MHC) Class I and II antigens, leukocyte common antigen CD45, intercellular adhesion molecule-1 (ICAM-1, CD54), the co- stimulatory molecules CD80 and CD86, CD95 as well as integrin CD11c. In contrast, DC expression of leukocyte function-associated-1 (LFA-1, CD11a), CD11b, CD18, CD40, and the DC DEC-205 receptor increased after the treatment. Changes in receptor levels occurred rapidly. DC MHC Class I and ICAM-1 expression declined to 40 percent of control levels by 2 hours post-PDT. DC treated with BPD-MA and light were poor stimulators of allogeneic T cells in the mixed leukocyte reaction. BPD-MA, in the absence of light, had no effect on the immunostimulatory properties of these cells. The changes in DC receptor expression pattern produced by BPD-MA and light were comparable to those produced by ultraviolet B light, a treatment known to alter the immunostimulatory characteristics of DC. Photodynamic therapy with BPD-MA represents an innovative approach for the modification of immune reactivity.

Studies on fate and toxicity of nanoalumina in male albino rats: Lethality, bioaccumulation and genotoxicity.

PubMed

Morsy, Gamal M; El-Ala, Kawther S Abou; Ali, Atef A

2016-02-01

The purpose of this study is to follow-up the distribution, lethality percentile doses (LDs) and bioaccumulation of aluminium oxide nanoparticles (Al2O3-NPs, average diameter 9.83 ± 1.61 nm) in some tissues of male albino rats, and to evaluate its genotoxicity to the brain tissues, during acute and sublethal experiments. The LDs of Al2O3-NPs, including median lethal dose (LD50), were estimated after intraperitoneal injection. The computed LD50 at 24 and 48 h were 15.10 and 12.88 g/kg body weight (b.w.), respectively. For acute experiments, the bioaccumulation of aluminium (Al) in the brain, liver, kidneys, intestine and spleen was estimated after 48 h of injection with a single acute dose (3.9, 6.4 and 8.5 g/kg b.w.), while for sublethal experiments it was after 1, 3, 7, 14 and 28 days of injection with 1.3 g/kg b.w. once in 2 days. Multi-way analysis of variance affirmed that Al uptake, in acute experiments, was significantly affected by the injected doses, organs (brain, liver, kidneys, intestine and spleen) and their interactions, while for sublethal experiments an altogether effect based on time (1, 3, 7, 14, 28 days), doses (0 and 1.3 g), organs and their interactions was reported. In addition, Al accumulated in the brain, liver, kidney, intestine and spleen of rats administered with Al2O3-NPs were significantly higher than the corresponding controls, during acute and sublethal experiments. The uptake of Al by the spleen of rats injected with acute doses was greater than that accumulated by kidney>brain>intestine>liver, whereas the brain of rats injected with sublethal dose accumulated lesser amount of Al followed by the kidney

Integrating multiple bioassays to detect and assess impacts of sublethal exposure to metal mixtures in an estuarine fish.

PubMed

Barbee, Nicole C; Ganio, Katherine; Swearer, Stephen E

2014-07-01

Estuaries are natural sinks for a wide range of urban, industrial and agricultural contaminants that accumulate at potentially toxic but non-lethal concentrations, yet we know relatively little about the long-term impacts of toxicants at these levels on aquatic organisms. In this study, we present an integrated, multi-pronged approach to detect and assess the impacts to estuarine fish of exposure to sublethal concentrations of metal mixtures. Our aims were to (1) examine the effects of sublethal metal exposure on the embryonic development of Galaxias maculatus, an estuarine spawning fish native to southeastern Australia, (2) determine whether sublethal exposure during development has knock-on effects on larval behaviour, and (3) establish whether a signature of metal exposure during embryogenesis can be detected in larval otoliths ("ear bones"). G. maculatus eggs are fertilised in water but develop aerially, in direct contact with estuarine sediments. We were thus also able to explore the relative importance of two exposure pathways, water and sediment. Embryos were exposed to two concentrations of a metal mixture containing Cu, Zn and Pb in water (during fertilisation) and on spiked sediments (during development), using a fully crossed experimental design. Overall, we found that exposure to the metal mixture reduced embryo survival and slowed embryonic development, resulting in poorer quality larvae that exhibited a reduced phototactic response. Differences in exposure to metals between treatment and control embryos were also permanently recorded in the developing otoliths. Combined these three approaches have the potential to be a powerful novel bioassessment tool as they provide a means of identifying a history of metal exposure during the embryonic period and linking it to suboptimal early growth and performance traits which could have long term fitness consequences. Copyright © 2014 Elsevier B.V. All rights reserved.

Toxicological responses of Laeonereis acuta (Polychaeta, Nereididae) after acute, subchronic and chronic exposure to cadmium.

PubMed

Dolagaratz Carricavur, Arantxa; Chiodi Boudet, Leila; Romero, María Belén; Polizzi, Paula; Marcovecchio, Jorge Eduardo; Gerpe, Marcela

2018-03-01

The objective of this study was to analyze the toxicological responses of the estuarine polychaete Laeonereis acuta after acute (96h), subchronic (7 days) and chronic (14 days) exposure to cadmium (Cd). Concentrations of metallothioneins (MT), lipid peroxidation (LPO), total Cd and metal-rich granules (MRG) were evaluated. Seasonal variations of MT and LPO levels in the wild were also measured. Polychaetes were obtained in the Quequén estuary located southeast of Buenos Aires Province, Argentina. For the acute toxicity assay, individuals were exposed to 10; 30, 65; 310; 600; 1300; 2000; 4300; 8100; 16300µgCdL -1 , which included levels of environmental relevance and median lethal concentrations (LC 50 ) for related species of polychaete. Based on 96h LC 50 values, polychaetes were exposed to sublethal doses of Cd. The concentrations for both subchronic and chronic assays were: 10; 30; 65; 310; 600; 1300; 2000; 4300µgCdL -1 . The 96h LC 50 value was 8234.9µgL -1 , which was within the values reported for other species of polychaete, indicating a high tolerance to Cd. MT induction was not observed for any time exposure. In additoin, LPO levels showed no differences with respect to control levels, which indicated an absence of oxidative damage caused by Cd. However, the total Cd and MRG-Cd concentrations in L. acuta in all tested treatments showed significant differences with respect to control levels. L. acuta were able to accumulate Cd in their tissues in the form of granules which are the main mechanism of Cd detoxification. Copyright © 2017 Elsevier Inc. All rights reserved.

Lethal Effect of CD3-Specific Antibody in Mice Deficient in TGF-β1 by Uncontrolled Flu-Like Syndrome1

PubMed Central

Perruche, Sylvain; Zhang, Pin; Maruyama, Takashi; Bluestone, Jeffrey A.; Saas, Philippe; Chen, WanJun

2010-01-01

CD3-specific Ab therapy results in a transient, self-limiting, cytokine-associated, flu-like syndrome in experimental animals and in patients, but the underlying mechanism for this spontaneous resolution remains elusive. By using an in vivo model of CD3-specific Ab-induced flu-like syndrome, we show in this paper that a single injection of sublethal dose of the Ab killed all TGF-β1−/− mice. The death of TGF-β1−/− mice was associated with occurrence of this uncontrolled flu-like syndrome, as demonstrated by a sustained storm of systemic inflammatory TNF and IFN-γ cytokines. We present evidence that deficiency of professional phagocytes to produce TGF-β1 after apoptotic T cell clearance may be responsible, together with hypersensitivity of T cells to both activation and apoptosis, for the uncontrolled inflammation. These findings indicate a key role for TGF-β1 and phagocytes in protecting the recipients from lethal inflammation and resolving the flu-like syndrome after CD3-specific Ab treatment. The study may also provide a novel molecular mechanism explaining the early death in TGF-β1−/− mice. PMID:19561097

Cell metal interactions: A comparison of natural uranium to other common metals in renal cells and bone osteoblasts

NASA Astrophysics Data System (ADS)

Milgram, S.; Carrière, M.; Thiebault, C.; Berger, P.; Khodja, H.; Gouget, B.

2007-07-01

Uranium acute intoxication has been documented to induce nephrotoxicity. Kidneys are the main target organs after short term exposures to high concentrations of the toxic, while chronic exposures lead to its accumulation in the skeleton. In this paper, chemical toxicity of uranium is investigated for rat osteoblastic bone cells and compared to results previously obtained on renal cells. We show that bone cells are less sensitive to uranium than renal cells. The influence of the chemical form on U cytotoxicity is demonstrated. For both cell types, a comparison of uranium toxicity with other metals or metalloids toxicities (Mn, Ni, Co, Cu, Zn, Se and Cd) permits classification of Cd, Zn, Se IV and Cu as the most toxic and Ni, Se VI, Mn and U as the least toxic. Chemical toxicity of natural uranium proves to be far less than that of cadmium. To try to explain the differences in sensitivities observed between metals and different cell types, cellular accumulations in cell monolayers are quantified by inductively coupled plasma-mass spectroscopy (ICP-MS), function of time or function of dose: lethal doses which simulate acute intoxications and sub-lethal doses which are more realistic with regard to environmentally metals concentrations. In addition to being more resistant, bone cells accumulated much more uranium than did renal cells. Moreover, for both cell models, Mn, U-citrate and U-bicarbonate are strongly accumulated whereas Cu, Zn and Ni are weakly accumulated. On the other hand, a strong difference in Cd behaviour between the two cell types is shown: whereas Cd is very weakly accumulated in bone cells, it is very strongly accumulated in renal cells. Finally, elemental distribution of the toxics is determined on a cellular scale using nuclear microprobe analysis. For both renal and osteoblastic cells, uranium was accumulated in as intracellular precipitates similar to those observed previously by SEM/EDS.

Haem peroxidase activity in Daphnia magna: a biomarker for sub-lethal toxicity assessments of kerosene-contaminated groundwater.

PubMed

Connon, Richard; Dewhurst, Rachel E; Crane, Mark; Callaghan, Amanda

2003-10-01

A novel biomarker was developed in Daphnia magna to detect organic pollution in groundwater. The haem peroxidase assay, which is an indirect means of measuring oxidase activity, was particularly sensitive to kerosene contamination. Exposure to sub-lethal concentrations of kerosene-contaminated groundwater resulted in a haem peroxidase activity increase by dose with a two-fold activity peak at 25%. Reproduction in D. magna remained unimpaired when exposed to concentrations below 25% for 21 days, and a decline in fecundity was only observed at concentrations above the peak in enzyme activity. The measurement of haem peroxidase activity in D. magna detected sublethal effects of kerosene in just 24 h, whilst offering information on the health status of the organisms. The biomarker may be useful in determining concentrations above which detrimental effects would occur from long-term exposure for fuel hydrocarbons. Moreover, this novel assay detects exposure to chemicals in samples that would normally be classified as non-toxic by acute toxicity tests.

RFID tracking of sublethal effects of two neonicotinoid insecticides on the foraging behavior of Apis mellifera.

PubMed

Schneider, Christof W; Tautz, Jürgen; Grünewald, Bernd; Fuchs, Stefan

2012-01-01

The development of insecticides requires valid risk assessment procedures to avoid causing harm to beneficial insects and especially to pollinators such as the honeybee Apis mellifera. In addition to testing according to current guidelines designed to detect bee mortality, tests are needed to determine possible sublethal effects interfering with the animal's vitality and behavioral performance. Several methods have been used to detect sublethal effects of different insecticides under laboratory conditions using olfactory conditioning. Furthermore, studies have been conducted on the influence insecticides have on foraging activity and homing ability which require time-consuming visual observation. We tested an experimental design using the radiofrequency identification (RFID) method to monitor the influence of sublethal doses of insecticides on individual honeybee foragers on an automated basis. With electronic readers positioned at the hive entrance and at an artificial food source, we obtained quantifiable data on honeybee foraging behavior. This enabled us to efficiently retrieve detailed information on flight parameters. We compared several groups of bees, fed simultaneously with different dosages of a tested substance. With this experimental approach we monitored the acute effects of sublethal doses of the neonicotinoids imidacloprid (0.15-6 ng/bee) and clothianidin (0.05-2 ng/bee) under field-like circumstances. At field-relevant doses for nectar and pollen no adverse effects were observed for either substance. Both substances led to a significant reduction of foraging activity and to longer foraging flights at doses of ≥0.5 ng/bee (clothianidin) and ≥1.5 ng/bee (imidacloprid) during the first three hours after treatment. This study demonstrates that the RFID-method is an effective way to record short-term alterations in foraging activity after insecticides have been administered once, orally, to individual bees. We contribute further information on the understanding of how honeybees are affected by sublethal doses of insecticides.

RFID Tracking of Sublethal Effects of Two Neonicotinoid Insecticides on the Foraging Behavior of Apis mellifera

PubMed Central

Schneider, Christof W.; Tautz, Jürgen; Grünewald, Bernd; Fuchs, Stefan

2012-01-01

The development of insecticides requires valid risk assessment procedures to avoid causing harm to beneficial insects and especially to pollinators such as the honeybee Apis mellifera. In addition to testing according to current guidelines designed to detect bee mortality, tests are needed to determine possible sublethal effects interfering with the animal's vitality and behavioral performance. Several methods have been used to detect sublethal effects of different insecticides under laboratory conditions using olfactory conditioning. Furthermore, studies have been conducted on the influence insecticides have on foraging activity and homing ability which require time-consuming visual observation. We tested an experimental design using the radiofrequency identification (RFID) method to monitor the influence of sublethal doses of insecticides on individual honeybee foragers on an automated basis. With electronic readers positioned at the hive entrance and at an artificial food source, we obtained quantifiable data on honeybee foraging behavior. This enabled us to efficiently retrieve detailed information on flight parameters. We compared several groups of bees, fed simultaneously with different dosages of a tested substance. With this experimental approach we monitored the acute effects of sublethal doses of the neonicotinoids imidacloprid (0.15–6 ng/bee) and clothianidin (0.05–2 ng/bee) under field-like circumstances. At field-relevant doses for nectar and pollen no adverse effects were observed for either substance. Both substances led to a significant reduction of foraging activity and to longer foraging flights at doses of ≥0.5 ng/bee (clothianidin) and ≥1.5 ng/bee (imidacloprid) during the first three hours after treatment. This study demonstrates that the RFID-method is an effective way to record short-term alterations in foraging activity after insecticides have been administered once, orally, to individual bees. We contribute further information on the understanding of how honeybees are affected by sublethal doses of insecticides. PMID:22253863

Sublethal Toxicity Endpoints of Heavy Metals to the Nematode Caenorhabditis elegans

PubMed Central

Wu, Yue; Wang, Qiang; Li, Huixin

2016-01-01

Caenorhabditis elegans, a free-living nematode, is commonly used as a model organism in ecotoxicological studies. The current literatures have provided useful insight into the relative sensitivity of several endpoints, but few direct comparisons of multiple endpoints under a common set of experimental conditions. The objective of this study was to determine appropriate sublethal endpoints to develop an ecotoxicity screening and monitoring system. C. elegans was applied to explore the sublethal toxicity of four heavy metals (copper, zinc, cadmium and chromium). Two physiological endpoints (growth and reproduction), three behavioral endpoints (head thrash frequency, body bend frequency and feeding) and two enzymatic endpoints (acetylcholine esterase [AChE] and superoxide dismutase [SOD]) were selected for the assessment of heavy metal toxicity. The squared correlation coefficients (R2) between the responses observed and fitted by Logit function were higher than 0.90 and the RMSE were lower than 0.10, indicating a good significance statistically. There was no significant difference among the half effect concentration (EC50) endpoints in physiological and behavioral effects of the four heavy metals, indicating similar sensitivity of physiological and behavioral effects. AChE enzyme was more sensitive to copper, zinc, and cadmium than to other physiological and behavioral effects, and SOD enzyme was most sensitive to chromium. The EC50 of copper, zinc, and cadmium, to the AChE enzyme in the nematodes were 0.68 mg/L, 2.76 mg/L, and 0.92 mg/L respectively and the EC50 of chromium to the SOD enzyme in the nematode was 1.58 mg/L. The results of this study showed that there was a good concentration-response relationship between all four heavy metals and the sublethal toxicity effects to C. elegans. Considering these sublethal endpoints in terms of simplicity, accuracy, repeatability and costs of the experiments, feeding is the relatively ideal sublethal toxicity endpoint of heavy metals to C. elegans. PMID:26824831

Impact of Chronic Neonicotinoid Exposure on Honeybee Colony Performance and Queen Supersedure

PubMed Central

Sandrock, Christoph; Tanadini, Matteo; Tanadini, Lorenzo G.; Fauser-Misslin, Aline; Potts, Simon G.; Neumann, Peter

2014-01-01

Background Honeybees provide economically and ecologically vital pollination services to crops and wild plants. During the last decade elevated colony losses have been documented in Europe and North America. Despite growing consensus on the involvement of multiple causal factors, the underlying interactions impacting on honeybee health and colony failure are not fully resolved. Parasites and pathogens are among the main candidates, but sublethal exposure to widespread agricultural pesticides may also affect bees. Methodology/Principal Findings To investigate effects of sublethal dietary neonicotinoid exposure on honeybee colony performance, a fully crossed experimental design was implemented using 24 colonies, including sister-queens from two different strains, and experimental in-hive pollen feeding with or without environmentally relevant concentrations of thiamethoxam and clothianidin. Honeybee colonies chronically exposed to both neonicotinoids over two brood cycles exhibited decreased performance in the short-term resulting in declining numbers of adult bees (−28%) and brood (−13%), as well as a reduction in honey production (−29%) and pollen collections (−19%), but colonies recovered in the medium-term and overwintered successfully. However, significantly decelerated growth of neonicotinoid-exposed colonies during the following spring was associated with queen failure, revealing previously undocumented long-term impacts of neonicotinoids: queen supersedure was observed for 60% of the neonicotinoid-exposed colonies within a one year period, but not for control colonies. Linked to this, neonicotinoid exposure was significantly associated with a reduced propensity to swarm during the next spring. Both short-term and long-term effects of neonicotinoids on colony performance were significantly influenced by the honeybees’ genetic background. Conclusions/Significance Sublethal neonicotinoid exposure did not provoke increased winter losses. Yet, significant detrimental short and long-term impacts on colony performance and queen fate suggest that neonicotinoids may contribute to colony weakening in a complex manner. Further, we highlight the importance of the genetic basis of neonicotinoid susceptibility in honeybees which can vary substantially. PMID:25084279

Impacts of neonicotinoid use on long-term population changes in wild bees in England.

PubMed

Woodcock, Ben A; Isaac, Nicholas J B; Bullock, James M; Roy, David B; Garthwaite, David G; Crowe, Andrew; Pywell, Richard F

2016-08-16

Wild bee declines have been ascribed in part to neonicotinoid insecticides. While short-term laboratory studies on commercially bred species (principally honeybees and bumblebees) have identified sub-lethal effects, there is no strong evidence linking these insecticides to losses of the majority of wild bee species. We relate 18 years of UK national wild bee distribution data for 62 species to amounts of neonicotinoid use in oilseed rape. Using a multi-species dynamic Bayesian occupancy analysis, we find evidence of increased population extinction rates in response to neonicotinoid seed treatment use on oilseed rape. Species foraging on oilseed rape benefit from the cover of this crop, but were on average three times more negatively affected by exposure to neonicotinoids than non-crop foragers. Our results suggest that sub-lethal effects of neonicotinoids could scale up to cause losses of bee biodiversity. Restrictions on neonicotinoid use may reduce population declines.

Impacts of neonicotinoid use on long-term population changes in wild bees in England

NASA Astrophysics Data System (ADS)

Woodcock, Ben A.; Isaac, Nicholas J. B.; Bullock, James M.; Roy, David B.; Garthwaite, David G.; Crowe, Andrew; Pywell, Richard F.

2016-08-01

Wild bee declines have been ascribed in part to neonicotinoid insecticides. While short-term laboratory studies on commercially bred species (principally honeybees and bumblebees) have identified sub-lethal effects, there is no strong evidence linking these insecticides to losses of the majority of wild bee species. We relate 18 years of UK national wild bee distribution data for 62 species to amounts of neonicotinoid use in oilseed rape. Using a multi-species dynamic Bayesian occupancy analysis, we find evidence of increased population extinction rates in response to neonicotinoid seed treatment use on oilseed rape. Species foraging on oilseed rape benefit from the cover of this crop, but were on average three times more negatively affected by exposure to neonicotinoids than non-crop foragers. Our results suggest that sub-lethal effects of neonicotinoids could scale up to cause losses of bee biodiversity. Restrictions on neonicotinoid use may reduce population declines.

Impacts of neonicotinoid use on long-term population changes in wild bees in England

PubMed Central

Woodcock, Ben A.; Isaac, Nicholas J. B.; Bullock, James M.; Roy, David B.; Garthwaite, David G.; Crowe, Andrew; Pywell, Richard F.

2016-01-01

Wild bee declines have been ascribed in part to neonicotinoid insecticides. While short-term laboratory studies on commercially bred species (principally honeybees and bumblebees) have identified sub-lethal effects, there is no strong evidence linking these insecticides to losses of the majority of wild bee species. We relate 18 years of UK national wild bee distribution data for 62 species to amounts of neonicotinoid use in oilseed rape. Using a multi-species dynamic Bayesian occupancy analysis, we find evidence of increased population extinction rates in response to neonicotinoid seed treatment use on oilseed rape. Species foraging on oilseed rape benefit from the cover of this crop, but were on average three times more negatively affected by exposure to neonicotinoids than non-crop foragers. Our results suggest that sub-lethal effects of neonicotinoids could scale up to cause losses of bee biodiversity. Restrictions on neonicotinoid use may reduce population declines. PMID:27529661

Peripheral Blood Biomarkers of Disease Outcome in a Monkey Model of Rift Valley Fever Encephalitis.

PubMed

Wonderlich, Elizabeth R; Caroline, Amy L; McMillen, Cynthia M; Walters, Aaron W; Reed, Douglas S; Barratt-Boyes, Simon M; Hartman, Amy L

2018-02-01

Rift Valley Fever (RVF) is an emerging arboviral disease of livestock and humans. Although the disease is caused by a mosquito-borne virus, humans are infected through contact with, or inhalation of, virus-laden particles from contaminated animal carcasses. Some individuals infected with RVF virus (RVFV) develop meningoencephalitis, resulting in morbidity and mortality. Little is known about the pathogenic mechanisms that lead to neurologic sequelae, and thus, animal models that represent human disease are needed. African green monkeys (AGM) exposed to aerosols containing RVFV develop a reproducibly lethal neurological disease that resembles human illness. To understand the disease process and identify biomarkers of lethality, two groups of 5 AGM were infected by inhalation with either a lethal or a sublethal dose of RVFV. Divergence between lethal and sublethal infections occurred as early as 2 days postinfection (dpi), at which point CD8 + T cells from lethally infected AGM expressed activated caspase-3 and simultaneously failed to increase levels of major histocompatibility complex (MHC) class II molecules, in contrast to surviving animals. At 4 dpi, lethally infected animals failed to demonstrate proliferation of total CD4 + and CD8 + T cells, in contrast to survivors. These marked changes in peripheral blood cells occur much earlier than more-established indicators of severe RVF disease, such as granulocytosis and fever. In addition, an early proinflammatory (gamma interferon [IFN-γ], interleukin 6 [IL-6], IL-8, monocyte chemoattractant protein 1 [MCP-1]) and antiviral (IFN-α) response was seen in survivors, while very late cytokine expression was found in animals with lethal infections. By characterizing immunological markers of lethal disease, this study furthers our understanding of RVF pathogenesis and will allow the testing of therapeutics and vaccines in the AGM model. IMPORTANCE Rift Valley Fever (RVF) is an important emerging viral disease for which we lack both an effective human vaccine and treatment. Encephalitis and neurological disease resulting from RVF lead to death or significant long-term disability for infected people. African green monkeys (AGM) develop lethal neurological disease when infected with RVF virus by inhalation. Here we report the similarities in disease course between infected AGM and humans. For the first time, we examine the peripheral immune response during the course of infection in AGM and show that there are very early differences in the immune response between animals that survive infection and those that succumb. We conclude that AGM are a novel and suitable monkey model for studying the neuropathogenesis of RVF and for testing vaccines and therapeutics against this emerging viral pathogen. Copyright © 2018 American Society for Microbiology.

Quantum Dot Nanotoxicity Assessment Using the Zebrafish Embryo

PubMed Central

King-Heiden, Tisha C.; Wiecinski, Paige N.; Mangham, Andrew N.; Metz, Kevin M.; Nesbit, Dorothy; Pedersen, Joel A.; Hamers, Robert J.; Heideman, Warren; Peterson, Richard E.

2009-01-01

Quantum dots (QDs) hold promise for several biomedical, life sciences and photovoltaic applications. Substantial production volumes and environmental release are anticipated. QD toxicity may be intrinsic to their physicochemical properties, or result from the release of toxic components during breakdown. We hypothesized that developing zebrafish could be used to identify and distinguish these different types of toxicity. Embryos were exposed to aqueous suspensions of CdSecore/ZnSshell QDs functionalized with either poly-L-lysine or poly(ethylene glycol) terminated with methoxy, carboxylate, or amine groups. Toxicity was influenced by the QD coating, which also contributed to the QD suspension stability. At sublethal concentrations, many QD preparations produced characteristic signs of Cd toxicity that weakly correlated with metallothionein expression, indicating that QDs are only slightly degraded in vivo. QDs also produced distinctly different toxicity that could not be explained by Cd release. Using the zebrafish model, we were able to distinguish toxicity intrinsic to QDs from that caused by released metal ions. We conclude that developing zebrafish provide a rapid, low- cost approach for assessing structure-toxicity relationships of nanoparticles. PMID:19350942

Genomic Analysis Reveals Distinct Concentration-Dependent Evolutionary Trajectories for Antibiotic Resistance in Escherichia coli

PubMed Central

Mogre, Aalap; Sengupta, Titas; Veetil, Reshma T.; Ravi, Preethi; Seshasayee, Aswin Sai Narain

2014-01-01

Evolution of bacteria under sublethal concentrations of antibiotics represents a trade-off between growth and resistance to the antibiotic. To understand this trade-off, we performed in vitro evolution of laboratory Escherichia coli under sublethal concentrations of the aminoglycoside kanamycin over short time durations. We report that fixation of less costly kanamycin-resistant mutants occurred earlier in populations growing at lower sublethal concentration of the antibiotic, compared with those growing at higher sublethal concentrations; in the latter, resistant mutants with a significant growth defect persisted longer. Using deep sequencing, we identified kanamycin resistance-conferring mutations, which were costly or not in terms of growth in the absence of the antibiotic. Multiple mutations in the C-terminal end of domain IV of the translation elongation factor EF-G provided low-cost resistance to kanamycin. Despite targeting the same or adjacent residues of the protein, these mutants differed from each other in the levels of resistance they provided. Analysis of one of these mutations showed that it has little defect in growth or in synthesis of green fluorescent protein (GFP) from an inducible plasmid in the absence of the antibiotic. A second class of mutations, recovered only during evolution in higher sublethal concentrations of the antibiotic, deleted the C-terminal end of the ATP synthase shaft. This mutation confers basal-level resistance to kanamycin while showing a strong growth defect in the absence of the antibiotic. In conclusion, the early dynamics of the development of resistance to an aminoglycoside antibiotic is dependent on the levels of stress (concentration) imposed by the antibiotic, with the evolution of less costly variants only a matter of time. PMID:25281544

Cadmium affects the mitochondrial viability and the acid soluble thiols concentration in liver, kidney, heart and gills of Ancistrus brevifilis (Eigenmann, 1920)

PubMed Central

Velasquez-Vottelerd, P.; Anton, Y.; Salazar-Lugo, R.

2015-01-01

The freshwater fish Ancistrus brevifilis, which is found in Venezuelan rivers, is considered a potential sentinel fish in ecotoxicological studies. The cadmium (Cd) effect on the mitochondrial viability (MV) and acid soluble thiols levels (AST) in A. brevifilis tissues (liver, kidney, heart, and gill) was evaluated. Forty-two fish with similar sizes and weights were randomly selected, of which 7 fish (with their respective replicate) were exposed for 7 and 30 days to a Cd sublethal concentration (0.1 mg.l-1). We determined the MV through a Janus Green B colorimetric assay and we obtained the concentration of AST by Ellman’s method. Mitochondrial viability decreased in fish exposed to Cd for 30 days with the liver being the most affected tissue. We also detected a significant decrease in AST levels was in fishes exposed to Cd for 7 days in liver and kidney tissues; these results suggests that AST levels are elevated in some tissues may act as cytoprotective and adaptive alternative mechanism related to the ROS detoxification, maintenance redox status and mitochondrial viability. Organ-specifics variations were observed in both assays. We conclude that the Cd exposure effect on AST levels and MV, vary across fish tissues and is related to the exposure duration, the molecule dynamics in different tissues, the organism and environmental conditions. PMID:26623384

c-Abl kinase inhibitors overcome CD40-mediated drug resistance in CLL: implications for therapeutic targeting of chemoresistant niches.

PubMed

Hallaert, Delfine Y H; Jaspers, Annelieke; van Noesel, Carel J; van Oers, Marinus H J; Kater, Arnon P; Eldering, Eric

2008-12-15

In lymph node (LN) proliferation centers in chronic lymphocytic leukemia (CLL), the environment protects from apoptotic and cytotoxic triggers. Here, we aimed to define the molecular basis for the increased drug resistance and searched for novel strategies to circumvent it. The situation in CLL LN could be mimicked by prolonged in vitro CD40 stimulation, which resulted in up-regulation of antiapoptotic Bcl-xL, A1/Bfl-1, and Mcl-1 proteins, and afforded resistance to various classes of drugs (fludarabine, bortezomib, roscovitine). CD40 stimulation also caused ERK-dependent reduction of Bim-EL protein, but ERK inhibition did not prevent drug resistance. Drugs combined with sublethal doses of the BH3-mimetic ABT-737 displayed partial and variable effects per individual CD40-stimulated CLL. The antiapoptotic profile of CD40-triggered CLL resembled BCR-Abl-dependent changes seen in chronic myeloid leukemia (CML), which prompted application of c-Abl inhibitors imatinib or dasatinib. Both compounds, but especially dasatinib, prevented the entire antiapoptotic CD40 program in CLL cells, and restored drug sensitivity. These effects also occurred in CLL samples with dysfunctional p53. Importantly, ex vivo CLL LN samples also displayed strong ERK activation together with high Bcl-xL and Mcl-1 but low Bim levels. These data indicate that CLL cells in chemoresistant niches may be sensitive to therapeutic strategies that include c-Abl inhibitors.

Sublethal exposure, insecticide resistance, and community stress

USDA-ARS?s Scientific Manuscript database

Although a prevalent pest management tool and anthropogenic stressors of widespread occurrence, insecticides are subject to biased perceptions and research demands largely guided by their use, market value, and regulatory requirements. As a result, short-term and simplistic efforts focusing on letha...

Costs of living for juvenile Chinook salmon (Oncorhynchus tshawytscha) in an increasingly warming and invaded world

USGS Publications Warehouse

Kuehne, Lauren M.; Olden, Julian D.; Duda, Jeffrey J.

2012-01-01

Rapid environmental change in freshwater ecosystems has created a need to understand the interactive effects of multiple stressors, with temperature and invasive predators identified as key threats to imperiled fish species. We tested the separate and interactive effects of water temperature and predation by non-native smallmouth bass (Micropterus dolomieu) on the lethal (mortality) and sublethal (behavior, physiology, and growth) effects for juvenile Chinook salmon (Oncorhynchus tshawytscha) in seminatural stream channel experiments. Over 48 h trials, there was no difference in direct predation with warmer temperatures, but significant interactive effects on sublethal responses of juvenile salmon. Warmer temperatures resulted in significantly stronger and more variable antipredator responses (surface shoaling and swimming activity), while physiological indicators (plasma glucose, plasma cortisol) suggested suppression of physiological mechanisms in response to the combined stressors. These patterns corresponded with additive negative growth in predation, temperature, and combined treatments. Our results suggest that chronic increases in temperature may not increase direct predation over short periods, but can result in significant sublethal costs with negative implications for long-term development, disease resistance, and subsequent size-selective mortality of Pacific salmon.

Immobilized Hydrolytic Enzymes Exhibit Antibiofilm Activity Against Escherichia coli at Sub-Lethal Concentrations.

PubMed

Villa, Federica; Secundo, Francesco; Polo, Andrea; Cappitelli, Francesca

2015-07-01

The effects of two commercially available immobilized enzymes (namely the glycosidase pectinase and the protease subtilisin A) at sub-lethal concentrations were investigated in terms of their influence on biofilm genesis, on the composition of the biofilm matrix, and their antibiotic synergy against Escherichia coli biofilm, used as a model system of bacterial biofilms. The best antibiofilm performance of solid-supported hydrolases was obtained at the surface concentration of 0.022 and 0.095 U/cm(2) with a reduction of 1.2 and 2.3 log CFU/biofilm for pectinase and subtilisin, respectively. At these enzyme surface concentrations, the biocatalysts affected the structural composition of the biofilm matrix, impacting biofilm thickness. Finally, the immobilized hydrolases enhanced biofilm sensitivity to a clinically relevant concentration of the antibiotic ampicillin. At the final antibiotic concentration of 0.1 mg/ml, a reduction of 2 and 3.5 log10 units in presence of 0.022 Upectinase/cm(2) and 0.095 Usubtilisin/cm(2) was obtained, respectively, in comparison the antibiotic alone. Immobilized pectinase and subtilisin at sub-lethal concentrations demonstrated a great potential for antibiofilm applications.

Sub-lethal and lethal toxicities of elevated CO2 on embryonic, juvenile, and adult stages of marine medaka Oryzias melastigma.

PubMed

Lee, Changkeun; Kwon, Bong-Oh; Hong, Seongjin; Noh, Junsung; Lee, Junghyun; Ryu, Jongseong; Kang, Seong-Gil; Khim, Jong Seong

2018-06-06

The potential leakage from marine CO 2 storage sites is of increasing concern, but few studies have evaluated the probable adverse effects on marine organisms. Fish, one of the top predators in marine environments, should be an essential representative species used for water column toxicity testing in response to waterborne CO 2 exposure. In the present study, we conducted fish life cycle toxicity tests to fully elucidate CO 2 toxicity mechanism effects. We tested sub-lethal and lethal toxicities of elevated CO 2 concentrations on marine medaka (Oryzias melastigma) at different developmental stages. At each developmental stage, the test species was exposed to varying concentrations of gaseous CO 2 (control air, 5%, 10%, 20%, and 30%), with 96 h of exposure at 0-4 d (early stage), 4-8 d (middle stage), and 8-12 d (late stage). Sub-lethal and lethal effects, including early developmental delays, cardiac edema, tail abnormalities, abnormal pigmentation, and mortality were monitored daily during the 14 d exposure period. At the embryonic stage, significant sub-lethal and lethal effects were observed at pH < 6.30. Hypercapnia can cause long-term and/or delayed developmental embryonic problems, even after transfer back to clean seawater. At fish juvenile and adult stages, significant mortality was observed at pH < 5.70, indicating elevated CO 2 exposure might cause various adverse effects, even during short-term exposure periods. It should be noted the early embryonic stage was found more sensitive to CO 2 exposure than other developmental stages of the fish life cycle. Overall, the present study provided baseline information for potential adverse effects of high CO 2 concentration exposure on fish developmental processes at different life cycle stages in marine ecosystems. Copyright © 2018 Elsevier Ltd. All rights reserved.

Bacterial Dose-Dependent Role of G Protein-Coupled Receptor Kinase 5 in Escherichia coli-Induced Pneumonia.

PubMed

Packiriswamy, Nandakumar; Steury, Michael; McCabe, Ian C; Fitzgerald, Scott D; Parameswaran, Narayanan

2016-05-01

G protein-coupled receptor kinase 5 (GRK5) is a serine/threonine kinase previously shown to mediate polymicrobial sepsis-induced inflammation. The goal of the present study was to examine the role of GRK5 in monomicrobial pulmonary infection by using an intratracheal Escherichia coli infection model of pneumonia. We used sublethal and lethal doses of E. coli to examine the mechanistic differences between low-grade and high-grade inflammation induced by E. coli infection. With a sublethal dose of E. coli, GRK5 knockout (KO) mice exhibited higher plasma CXCL1/KC levels and enhanced lung neutrophil recruitment early after infection, and lower bacterial loads, than wild-type (WT) mice. The inflammatory response was also diminished, and resolution of inflammation advanced, in the lungs of GRK5 KO mice. In contrast to the reduced bacterial loads in GRK5 KO mice following a sublethal dose, at a lethal dose of E. coli, the bacterial burdens remained high in GRK5 KO mice relative to those in WT mice. This occurred in spite of enhanced plasma CXCL1 levels as well as neutrophil recruitment in the KO mice. But the recruited neutrophils (following high-dose infection) exhibited decreased CD11b expression and reduced reactive oxygen species production, suggesting decreased neutrophil activation or increased neutrophil exhaustion in the GRK5 KO mice. In agreement with the increased bacterial burden, KO mice showed poorer survival than WT mice following E. coli infection at a lethal dose. Overall, our data suggest that GRK5 negatively regulates CXCL1/KC levels during bacterial pneumonia but that the role of GRK5 in the clinical outcome in this model is dependent on the bacterial dose. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Agar Underlay Method for Recovery of Sublethally Heat-Injured Bacteria

PubMed Central

Kang, D. H.; Siragusa, G. R.

1999-01-01

A method of recovering sublethally heat-injured bacteria was developed. The procedure (termed the agar underlay method) uses a nonselective agar underlaid with a selective medium. In a two-chambered petri dish, the Lutri plate (LP), a nonselective agar is inoculated with a population of sublethally heat-injured bacteria. After a 2-h repair incubation period, selective agar is added to the bottom chamber of the LP and incubated. By diffusing through the nonselective top agar, selective agents from the underlay medium impart selectivity to the system. By the agar underlay method, recovery rates of the heat-injured food-borne pathogens Escherichia coli O157:H7 and Salmonella typhimurium were not different (P > 0.05) from recovery rates determined with nonselective media. Sublethally heat-injured cells (60°C for 1.5 min in buffer or 80°C for 30 s on meat surfaces) grew and produced a typical colony morphology and color reaction when the agar underlay procedure was used with the appropriate respective selective agars. Unlike agar overlay methods for injury repair, the agar underlay procedure allows the typical selective-medium colony morphology to develop and allows colonies to be more easily picked for further characterization. Higher recovery rates of heat-injured fecal enterococci from bovine fecal samples and total coliforms from animal waste lagoons were obtained by the agar underlay method with selective agars than by direct plating on the respective selective media. PMID:10583985

Sublethal effects of imidacloprid on the fecundity, longevity, and enzyme activity of Sitobion avenae (Fabricius) and Rhopalosiphum padi (Linnaeus).

PubMed

Lu, Y-H; Zheng, X-S; Gao, X-W

2016-08-01

The aphid species Sitobion avenae and Rhopalosiphum padi are the most important pests in wheat growing regions of many countries. In this study, we investigated the sublethal effects of imidacloprid on fecundity, longevity, and enzyme activity in both aphid species by comparing 3-h exposure for one or three generations. Our results indicated that 3-h exposure to sublethal doses of imidacloprid for one generation had no discernible effect on the survival, fecundity, longevity, or enzyme activity levels of aphids. However, when pulse exposures to imidacloprid were sustained over three generations, both fecundity and longevity were significantly decreased in both S. avenae and R. padi. Interestingly, the fecundity of R. padi had almost recovered by the F5 generation, but its longevity was still deleteriously affected. These results indicated that R. padi laid eggs in shorter time lags and has a more fast resilience. The change in reproduction behavior may be a phenomenon of R. padi to compensate its early death. If this is stable for the next generation, it means that the next generation is more competitive than unexposed populations, which could be the reason underlying population outbreaks that occur after longer-term exposure to an insecticide. This laboratory-based study highlights the sublethal effects of imidacloprid on the longevity and fecundity of descendants and provides an empirical basis from which to consider management decisions for chemical control in the field.

Sublethal dose of phoxim and Bombyx mori nucleopolyhedrovirus interact to elevate silkworm mortality.

PubMed

Gu, ZhiYa; Li, FanChi; Hu, JingSheng; Ding, Chao; Wang, Chaoqian; Tian, JiangHai; Xue, Bin; Xu, KaiZun; Shen, WeiDe; Li, Bing

2017-03-01

Silkworm (Bombyx mori) is an economically important insect. It is relatively less resistant to certain chemicals and environment exposures such as pesticides and pathogens. After pesticide exposures, the silkworms are more susceptible to microbial infections. The mechanism underlying the susceptibility might be related to immune response and oxidative stress. A sublethal dose of phoxim combined with Bombyx mori nucleopolyhedrovirus (BmNPV) elevated the silkworm mortality at 96 h. We found a higher content of H 2 O 2 and increased levels of genes related to oxidative stress and immune response after treatment with a sublethal dose of phoxim for 24 h or 48 h. However, such response decreased with longer pesticide treatment. Mortality increased by 44% when B. mori was exposed to combined treatment with BmNPV and phoxim rather than BmNPV alone. The level of examined immune-related and oxidative-stress-related genes significantly decreased in the combined treatment group compared with the BmNPV group. Our results indicated that, with long-term exposure to pesticides such as OPs, even at sublethal dose, the oxidative stress response and immune responses in silkworm were inhibited, which may lead to further immune impairment and accumulation of oxidative stress, resulting in susceptibility to the virus and harm to the silkworm. Our study provided insights for understanding the susceptibility to pathogen after pesticide exposures, which may promote the development of better pesticide controls to avoid significant economic losses. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Contaminant Hazard Reviews. [Reports No. 1-28 on CD-ROM.

USGS Publications Warehouse

Eisler, R.

1998-01-01

This compact disc (CD) contains the first 28 reports in the Contaminant Hazard Reviews (CHR) that were published originally between 1985 and 1994 in the U.S. Department of the Interior Biological Report series. The CD was produced because printed supplies of these reviews--a total of 84,000--became exhausted and demand remained high. Each review was prepared at the request of environmental specialists of the U.S. Fish and Wildlife Service and each contained specific information on mirex, cadmium, carbofuran, toxaphene, selenium, chromium, polychlorinated biphenyls, dioxins, diazinon, mercury, polycyclic aromatic hydrocarbons, arsenic, chlorpyrifos, lead, tin, index issue, pentachlorophenol, atrazine, molybdenum, boron, chlordane, paraquat, cyanide, fenvalerate, diflubenzuron, zinc, famphur, or acrolein. Each report reviewed and synthesized the technical literature on a single contaminant and its effects on terrestrial plants and invertebrates, aquatic plants and animals, avian and mammalian wildlife, and other natural resources. The subtopics include contaminant sources and uses; physical, chemical, and metabolic properties; concentrations in field collections of abiotic materials and living organisms; deficiency effects, where appropriate; lethal and sublethal effects, including effects on survival, growth, reproduction, metabolism, mutagenicity, teratogenicity, and carcinogenicity; proposed criteria for the protection of human health and sensitive natural resources; and recommendations for additional research.

Sensivity of Adult Reproduction and Reproductive Development in Japanese Medaka Exposed to 4-Tert-octylphenol

EPA Science Inventory

In response to legislation, the USEPA is developing assessment tools for identifying chemicals likely to cause sublethal effects on reproduction and reproductive development with ultimate adverse impacts on fish populations. While fecundity and fertility data from short-term adul...

Toll-like receptors 2 and 4 contribute to sepsis-induced depletion of spleen dendritic cells.

PubMed

Pène, Frédéric; Courtine, Emilie; Ouaaz, Fatah; Zuber, Benjamin; Sauneuf, Bertrand; Sirgo, Gonzalo; Rousseau, Christophe; Toubiana, Julie; Balloy, Viviane; Chignard, Michel; Mira, Jean-Paul; Chiche, Jean-Daniel

2009-12-01

Depletion of dendritic cells (DC) in secondary lymphoid organs is a hallmark of sepsis-induced immune dysfunction. In this setting, we investigated if Toll-like receptor (TLR)-dependent signaling might modulate the maturation process and the survival of DC. Using a model of sublethal polymicrobial sepsis induced by cecal ligation and puncture, we investigated the quantitative and functional features of spleen DC in wild-type, TLR2(-/-), TLR4(-/-), and TLR2(-/-) TLR4(-/-) mice. By 24 h, a decrease in the relative percentage of CD11c(high) spleen DC occurred in wild-type mice but was prevented in TLR2(-/-), TLR4(-/-), and TLR2(-/-) TLR4(-/-) mice. In wild-type mice, sepsis dramatically affected both CD11c(+) CD8alpha(+) and CD11c(+) CD8alpha(-) subsets. In all three types of knockout mice studied, the CD11c(+) CD8alpha(+) subset followed a depletion pattern similar to that for wild-type mice. In contrast, the loss of CD11c(+) CD8alpha(-) cells was attenuated in TLR2(-/-) and TLR4(-/-) mice and completely prevented in TLR2(-/-) TLR4(-/-) mice. Accordingly, apoptosis of spleen DC was increased in septic wild-type mice and inhibited in knockout mice. In addition we characterized the functional features of spleen DC obtained from septic mice. As shown by increased expression of major histocompatibility complex class II and CD86, polymicrobial sepsis induced maturation of DC, with subsequent increased capacity to prime T lymphocytes, similarly in wild-type and knockout mice. In response to CpG DNA stimulation, production of interleukin-12 was equally impaired in DC obtained from wild-type and knockout septic mice. In conclusion, although dispensable for the DC maturation process, TLR2 and TLR4 are involved in the mechanisms leading to depletion of spleen DC following polymicrobial sepsis.

Effects of Sublethal Cadmium Exposure on Antipredator Behavioural and Antitoxic Responses in the Invasive Amphipod Dikerogammarus villosus

PubMed Central

Sornom, Pascal; Gismondi, Eric; Vellinger, Céline; Devin, Simon; Férard, Jean-François; Beisel, Jean-Nicolas

2012-01-01

Amphipods are recognised as an important component of freshwater ecosystems and are frequently used as an ecotoxicological test species. Despite this double interest, there is still a lack of information concerning toxic impacts on ecologically relevant behaviours. The present study investigated the influence of cadmium (Cd), a non-essential heavy metal, on both antipredator behaviours and antitoxic responses in the invasive amphipod Dikerogammarus villosus under laboratory conditions. Amphipod behaviour (i.e. refuge use, aggregation with conspecifics, exploration and mobility) was recorded following a 4-min test-exposure to 500 µg Cd/L with or without a 24-h Cd pre-exposure and in the presence or absence of a high perceived risk of predation (i.e. water scented by fish predators and injured conspecifics). Following behavioural tests, malondialdehyde (MDA) levels, a biomarker for toxic effect, and energy reserves (i.e. lipid and glycogen contents) were assessed. Cd exposures induced (1) cell damage reflected by high MDA levels, (2) erratic behaviour quantified by decreasing refuge use and exploration, and increasing mobility, and (3) a depletion in energy reserves. No significant differences were observed between 4-min test-exposed and 24-h pre-exposed individuals. Gammarids exposed to Cd had a disturbed perception of the alarm stimuli, reflected by increased time spent outside of refuges and higher mobility compared to gammarids exposed to unpolluted water. Our results suggest that Cd exposure rapidly disrupts the normal behavioural responses of gammarids to alarm substances and alters predator-avoidance strategies, which could have potential impacts on aquatic communities. PMID:22879985

Biomarkers assessment in the peacock blenny Salaria pavo exposed to cadmium.

PubMed

Naïja, Azza; Marchand, Justine; Kestemont, Patrick; Haouas, Zohra; Blust, Ronny; Chénais, Benoit; Helal, Ahmed Noureddine

2016-08-01

Cadmium (Cd) is one of the most toxic metals and is widely distributed in freshwater and marine environments. It has received much attention from a toxicological perspective. The aim of this study was to assess the effect of Cd in the peacock blenny Salaria pavo, a species of the family of blennies that was used as bioindicator of water pollution. We performed a sublethal contamination of fish to 2 mg CdCl2 L(-1) during 1, 4, 10, and 15 days. Cd accumulation was measured in gills and liver and displayed a significant increase of its concentration throughout the experiment, with slightly higher levels in the liver, except after 4 days. Partial-length cDNA of mt1, mt2, mnsod, cuznsod, cat, and gpx were characterized. Results from mRNA expression levels displayed an up-regulation of mt2 and mnsod. Biomarker activities were determined in gills and liver. In gills, data displayed an inhibition of EROD and GST activities. Cd exposure significantly increased GPx activities but did not affect CAT levels throughout the experiment. No LPO induction was observed in gills of exposed fish. Regarding the liver, the activity of all enzymes and MDA levels increased significantly from the beginning of the experiment except EROD that increased after 15 days of contamination only. At the histological level, fish exhibited pathological symptoms in gills and liver with a predominance of circulatory disturbances in gills and regressive changes in the liver. Our results displayed that peacock blennies are able to survive Cd toxicity due to various physiological adaptation mechanisms.

Whole-body irradiation increases the magnitude and persistence of adoptively transferred T cells associated with tumor regression in a mouse model of prostate cancer

PubMed Central

Ward-Kavanagh, Lindsay K.; Zhu, Junjia; Cooper, Timothy K.; Schell, Todd D.

2014-01-01

Adoptive immunotherapy has demonstrated efficacy in a subset of clinical and preclinical studies, but the T cells used for therapy often are rendered rapidly non-functional in tumor-bearing hosts. Recent evidence indicates that prostate cancer can be susceptible to immunotherapy, but most studies using autochthonous tumor models demonstrate only short-lived T-cell responses in the tolerogenic prostate microenvironment. Here, we assessed the efficacy of sublethal whole-body irradiation (WBI) to enhance the magnitude and duration of adoptively transferred CD8+ T cells in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. We demonstrate that WBI promoted high-level accumulation of granzyme B (GzB)-expressing donor T cells both in lymphoid organs and in the prostate of TRAMP mice. Donor T cells remained responsive to vaccination in irradiated recipients, but a single round of WBI-enhanced adoptive immunotherapy failed to impact significantly the existing disease. Addition of a second round of immunotherapy promoted regression of established disease in half of the treated mice, with no progressions observed. Regression was associated with long-term persistence of effector/memory phenotype CD8+ donor cells. Administration of the second round of adoptive immunotherapy led to reacquisition of GzB expression by persistent T cells from the first transfer. These results indicate that WBI conditioning amplifies tumor-specific T cells in the TRAMP prostate and lymphoid tissue, and suggest that the initial treatment alters the tolerogenic microenvironment to increase antitumor activity by a second wave of donor cells. PMID:24801834

"Use of acidophilic bacteria of the genus Acidithiobacillus to biosynthesize CdS fluorescent nanoparticles (quantum dots) with high tolerance to acidic pH".

PubMed

Ulloa, G; Collao, B; Araneda, M; Escobar, B; Álvarez, S; Bravo, D; Pérez-Donoso, J M

2016-12-01

The use of bacterial cells to produce fluorescent semiconductor nanoparticles (quantum dots, QDs) represents a green alternative with promising economic potential. In the present work, we report for the first time the biosynthesis of CdS QDs by acidophilic bacteria of the Acidithiobacillus genus. CdS QDs were obtained by exposing A. ferrooxidans, A. thiooxidans and A. caldus cells to sublethal Cd 2+ concentrations in the presence of cysteine and glutathione. The fluorescence of cadmium-exposed cells moves from green to red with incubation time, a characteristic property of QDs associated with nanocrystals growth. Biosynthesized nanoparticles (NPs) display an absorption peak at 360nm and a broad emission spectra between 450 and 650nm when excited at 370nm, both characteristic of CdS QDs. Average sizes of 6 and 10nm were determined for green and red NPs, respectively. The importance of cysteine and glutathione on QDs biosynthesis in Acidithiobacillus was related with the generation of H 2 S. Interestingly, QDs produced by acidophilic bacteria display high tolerance to acidic pH. Absorbance and fluorescence properties of QDs was not affected at pH 2.0, a condition that totally inhibits the fluorescence of QDs produced chemically or biosynthesized by mesophilic bacteria (stable until pH 4.5-5.0). Results presented here constitute the first report of the generation of QDs with improved properties by using extremophile microorganisms. Copyright © 2016 Elsevier Inc. All rights reserved.

Free Radical Pathology of the Body in the Long-Term Period under Combined Exposure to Gamma Radiation and Emotional Stress in the Experiment

ERIC Educational Resources Information Center

Ilderbayeva, Gulzhan O.; Suleymeneva, Dametken M.; Ilderbayev, ?ralbek Z.; Argynbekova, Ainur S.; Berekenova, Gulnar A.; Syzdykaeva, Sayrangul M.; Kabdykanov, Symbat K.

2016-01-01

We have studied the intensity of free radical and antioxidant processes in organs (liver, spleen, thymus, lymph nodes of the small intestine, and adrenal glands) and cells (lymphocytes) in the long-term period after combined exposure to a sublethal dose of ?-radiation (6 Gy) and emotional stress. Combined exposure was followed by accumulation of…

A neonicotinoid impairs olfactory learning in Asian honey bees (Apis cerana) exposed as larvae or as adults

PubMed Central

Tan, Ken; Chen, Weiwen; Dong, Shihao; Liu, Xiwen; Wang, Yuchong; Nieh, James C.

2015-01-01

Xenobiotics such as the neonicotinoid pesticide, imidacloprid, are used globally, but their effects on native bee species are poorly understood. We studied the effects of sublethal doses of imidacloprid on olfactory learning in the native honey bee species, Apis cerana, an important pollinator of agricultural and native plants throughout Asia. We provide the first evidence that imidacloprid can impair learning in A. cerana workers exposed as adults or as larvae. Adults that ingested a single imidacloprid dose as low as 0.1 ng/bee had significantly reduced olfactory learning acquisition, which was 1.6-fold higher in control bees. Longer-term learning (1-17 h after the last learning trial) was also impaired. Bees exposed as larvae to a total dose of 0.24 ng/bee did not have reduced survival to adulthood. However, these larval-treated bees had significantly impaired olfactory learning when tested as adults: control bees exhibited up to 4.8-fold better short-term learning acquisition, though longer-term learning was not affected. Thus, sublethal cognitive deficits elicited by neonicotinoids on a broad range of native bee species deserve further study. PMID:26086769

An analysis of lethal and sublethal interactions among type I and type II pyrethroid pesticide mixtures using standard Hyalella azteca water column toxicity tests.

PubMed

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.

Chronic Exposure of Corals to Fine Sediments: Lethal and Sub-Lethal Impacts

PubMed Central

Flores, Florita; Hoogenboom, Mia O.; Smith, Luke D.; Cooper, Timothy F.; Abrego, David; Negri, Andrew P.

2012-01-01

Understanding the sedimentation and turbidity thresholds for corals is critical in assessing the potential impacts of dredging projects in tropical marine systems. In this study, we exposed two species of coral sampled from offshore locations to six levels of total suspended solids (TSS) for 16 weeks in the laboratory, including a 4 week recovery period. Dose-response relationships were developed to quantify the lethal and sub-lethal thresholds of sedimentation and turbidity for the corals. The sediment treatments affected the horizontal foliaceous species (Montipora aequituberculata) more than the upright branching species (Acropora millepora). The lowest sediment treatments that caused full colony mortality were 30 mg l−1 TSS (25 mg cm−2 day−1) for M. aequituberculata and 100 mg l−1 TSS (83 mg cm−2 day−1) for A. millepora after 12 weeks. Coral mortality generally took longer than 4 weeks and was closely related to sediment accumulation on the surface of the corals. While measurements of damage to photosystem II in the symbionts and reductions in lipid content and growth indicated sub-lethal responses in surviving corals, the most reliable predictor of coral mortality in this experiment was long-term sediment accumulation on coral tissue. PMID:22662225

Systemic delivery of microencapsulated 3-bromopyruvate for the therapy of pancreatic cancer.

PubMed

Chapiro, Julius; Sur, Surojit; Savic, Lynn Jeanette; Ganapathy-Kanniappan, Shanmugasundaram; Reyes, Juvenal; Duran, Rafael; Thiruganasambandam, Sivarajan Chettiar; Moats, Cassandra Rae; Lin, MingDe; Luo, Weibo; Tran, Phuoc T; Herman, Joseph M; Semenza, Gregg L; Ewald, Andrew J; Vogelstein, Bert; Geschwind, Jean-François

2014-12-15

This study characterized the therapeutic efficacy of a systemically administered formulation of 3-bromopyruvate (3-BrPA), microencapsulated in a complex with β-cyclodextrin (β-CD), using an orthotopic xenograft mouse model of pancreatic ductal adenocarcinoma (PDAC). The presence of the β-CD-3-BrPA complex was confirmed using nuclear magnetic resonance spectroscopy. Monolayer as well as three-dimensional organotypic cell culture was used to determine the half-maximal inhibitory concentrations (IC50) of β-CD-3-BrPA, free 3-BrPA, β-CD (control), and gemcitabine in MiaPaCa-2 and Suit-2 cell lines, both in normoxia and hypoxia. Phase-contrast microscopy, bioluminescence imaging (BLI), as well as zymography and Matrigel assays were used to characterize the effects of the drug in vitro. An orthotopic lucMiaPaCa-2 xenograft tumor model was used to investigate the in vivo efficacy. β-CD-3-BrPA and free 3-BrPA demonstrated an almost identical IC50 profile in both PDAC cell lines with higher sensitivity in hypoxia. Using the Matrigel invasion assay as well as zymography, 3-BrPA showed anti-invasive effects in sublethal drug concentrations. In vivo, animals treated with β-CD-3-BrPA demonstrated minimal or no tumor progression as evident by the BLI signal as opposed to animals treated with gemcitabine or the β-CD (60-fold and 140-fold signal increase, respectively). In contrast to animals treated with free 3-BrPA, no lethal toxicity was observed for β-CD-3-BrPA. The microencapsulation of 3-BrPA represents a promising step towards achieving the goal of systemically deliverable antiglycolytic tumor therapy. The strong anticancer effects of β-CD-3-BrPA combined with its favorable toxicity profile suggest that clinical trials, particularly in patients with PDAC, should be considered. ©2014 American Association for Cancer Research.

Blue light treatment of Pseudomonas aeruginosa: Strong bactericidal activity, synergism with antibiotics and inactivation of virulence factors.

PubMed

Fila, Grzegorz; Kawiak, Anna; Grinholc, Mariusz Stanislaw

2017-08-18

Pseudomonas aeruginosa is among the most common pathogens responsible for both acute and chronic infections of high incidence and severity. Additionally, P. aeruginosa resistance to conventional antimicrobials has increased rapidly over the past decade. Therefore, it is crucial to explore new therapeutic options, particularly options that specifically target the pathogenic mechanisms of this microbe. The ability of a pathogenic bacterium to cause disease is dependent upon the production of agents termed 'virulence factors', and approaches to mitigate these agents have gained increasing attention as new antibacterial strategies. Although blue light irradiation is a promising alternative approach, only limited and preliminary studies have described its effect on virulence factors. The current study aimed to investigate the effects of lethal and sub-lethal doses of blue light treatment (BLT) on P. aeruginosa virulence factors. We analyzed the inhibitory effects of blue light irradiation on the production/activity of several virulence factors. Lethal BLT inhibited the activity of pyocyanin, staphylolysin, pseudolysin and other proteases, but sub-lethal BLT did not affect the production/expression of proteases, phospholipases, and flagella- or type IV pili-associated motility. Moreover, a eukaryotic cytotoxicity test confirmed the decreased toxicity of blue light-treated extracellular P. aeruginosa fractions. Finally, the increased antimicrobial susceptibility of P. aeruginosa treated with sequential doses of sub-lethal BLT was demonstrated with a checkerboard test. Thus, this work provides evidence-based proof of the susceptibility of drug-resistant P. aeruginosa to BLT-mediated killing, accompanied by virulence factor reduction, and describes the synergy between antibiotics and sub-lethal BLT.

Use of an innovative T-tube maze assay and the proboscis extension response assay to assess sublethal effects of GM products and pesticides on learning capacity of the honey bee Apis mellifera L.

PubMed

Han, Peng; Niu, Chang-Ying; Lei, Chao-Liang; Cui, Jin-Jie; Desneux, Nicolas

2010-11-01

Transgenic Cry1Ac+CpTI cotton (CCRI41) is a promising cotton cultivar throughout China but side effects and especially sublethal effects of this transgenic cultivar on beneficial insects remain poorly studied. More specifically potential sublethal effects on behavioural traits of the honey bee Apis mellifera L. have not been formally assessed despite the importance of honey bees for pollination. The goal of our study was to assess potential effects of CCRI41 cotton pollen on visual and olfactory learning by honey bees. After a 7-day oral chronic exposure to honey mixed with either CCRI41 pollen, imidacloprid-treated conventional pollen (used as positive sublethal control) or conventional pollen (control), learning performance was evaluated by the classical proboscis extension reflex (PER) procedure as well as a T-tube maze test. The latter assay was designed as a new device to assess potential side effects of pesticides on visual associative learning of honey bees. These two procedures were complementary because the former focused on olfactory learning while the latter was involved in visual learning based on visual orientation ability. Oral exposure to CCRI41 pollen did not affect learning capacities of honey bees in both the T-tube maze and PER tests. However, exposure to imidacloprid resulted in reduced visual learning capacities in T-tube maze evaluation and decreased olfactory learning performances measured with PER. The implications of these results are discussed in terms of risks of transgenic CCRI41 cotton crops for honey bees.

Serum microRNAs are early indicators of survival after radiation-induced hematopoietic injury

PubMed Central

Acharya, Sanket S.; Fendler, Wojciech; Watson, Jacqueline; Hamilton, Abigail; Pan, Yunfeng; Gaudiano, Emily; Moskwa, Patryk; Bhanja, Payel; Saha, Subhrajit; Guha, Chandan; Parmar, Kalindi; Chowdhury, Dipanjan

2015-01-01

Accidental radiation exposure is a threat to human health that necessitates effective clinical planning and diagnosis. Minimally invasive biomarkers that can predict long-term radiation injury are urgently needed for optimal management after a radiation accident. We have identified serum microRNA (miRNA) signatures that indicate long-term impact of total body irradiation (TBI) in mice when measured within 24 hours of exposure. Impact of TBI on the hematopoietic system was systematically assessed to determine a correlation of residual hematopoietic stem cells (HSCs) with increasing doses of radiation. Serum miRNA signatures distinguished untreated mice from animals exposed to radiation and correlated with the impact of radiation on HSCs. Mice exposed to sublethal (6.5 Gy) and lethal (8 Gy) doses of radiation were indistinguishable for 3 to 4 weeks after exposure. A serum miRNA signature detectable 24 hours after radiation exposure consistently segregated these two cohorts. Furthermore, using either a radioprotective agent before, or radiation mitigation after, lethal radiation, we determined that the serum miRNA signature correlated with the impact of radiation on animal health rather than the radiation dose. Last, using humanized mice that had been engrafted with human CD34+ HSCs, we determined that the serum miRNA signature indicated radiation-induced injury to the human bone marrow cells. Our data suggest that serum miRNAs can serve as functional dosimeters of radiation, representing a potential breakthrough in early assessment of radiation-induced hematopoietic damage and timely use of medical countermeasures to mitigate the long-term impact of radiation. PMID:25972001

Lethal and sub-lethal effects on the Asian common toad Duttaphrynus melanostictus from exposure to hexavalent chromium.

PubMed

Fernando, Vindhya A K; Weerasena, Jagathpriya; Lakraj, G Pemantha; Perera, Inoka C; Dangalle, Chandima D; Handunnetti, Shiroma; Premawansa, Sunil; Wijesinghe, Mayuri R

2016-08-01

Chromium discharged in industrial effluents frequently occurs as an environmental pollutant, but the lethal and sub-lethal effects the heavy metal might cause in animals exposed to it have been insufficiently investigated. Selecting the amphibian Duttaphrynus melanostictus, we carried out laboratory tests to investigate the effects of short and long term exposure to hexavalent chromium (Cr(VI)) in both tadpoles and adult toads. The concentrations used were 0.002, 0.02, 0.2, 1.0 and 2.0mg/L, the first three corresponding to field levels. In vitro exposures were also carried out using toad erythrocytes and Cr(VI) concentrations of 0.0015, 0.003, 0.015, 0.03, 0.15mg/L. Mortality, growth retardation, developmental delays and structural aberrations were noted in the metal-treated tadpoles, with increasing incidence corresponding to increase in Cr(VI) level and duration of exposure. Many of the sub-lethal effects were evident with long term exposure to environmentally relevant levels of the toxicant. Changes in selected blood parameters and erythrocyte morphometry were also detected in Cr(VI) exposed toads, indicating anaemic and leucopenic conditions. In the genotoxicity study, DNA damage indicated by comet assay and increased micronuclei frequency, occurred at the low Cr(VI) concentrations tested. The multiple deleterious effects of exposure to chromium signal the need for monitoring and controlling the discharge of chromium to the environment. The dose-dependency and genotoxic effects observed in this widely distributed Asian toad indicates its suitability for monitoring heavy metal pollution in aquatic systems. Copyright © 2016 Elsevier B.V. All rights reserved.

[Anti-mouse CD122 antibody promotes the hematopoietic repopulating capacity of cord blood CD34⁺ cells in NOD/SCID mice].

PubMed

Sheng, Men-Yao; Shi, Hui; Xing, Wen; Wang, Wen-Jun; Si, Xiao-Hui; Bai, Jie; Yuan, Wei-Ping; Zhou, Yuan; Yang, Feng-Chun

2014-12-01

The study was aimed to investigate the effect of anti-mouse CD122 antibody on the hematopoietic repopulating capacity of cord blood CD34⁺ cells in a humanized murine model-non obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. After sublethal irradiation with γ-ray, NOD/SCID mice were intraperitoneally injected with 200 µg mouse isotype control antibody or anti-mouse CD122 antibody. Human cord blood CD34⁺ cells or phosphate-buffered saline (PBS) were injected via the tail vein at 6-8 hours later. Cohort of the mice injected with anti-mice CD122 antibody or control antibody alone were sacrificed at different time point (at week 2, 3, and 4 weeks) after the injection, and the percentage of NK cells in the peripheral blood was analyzed by flow cytometry. To evaluate the effect of anti-mouse CD122 antibody on the repopulating capacity of cord blood CD34⁺ cells in the recipient mice, phenotype analysis was performed in the bone marrow at 6 and 8 weeks after the transplantation. The results showed that the proportion of NK cells in the peripheral blood were (4.6 ± 0.6)% and (5.7 ± 1.7)% at week 2 and 3 after anti-CD122 antibody injection respectively,which decreased by 60%, compared with the mice injected with isotype control antibody. After 6 and 8 weeks of cord blood CD34⁺ cell transplantation,the percentage of human CD45⁺ in the bone marrow of the recipient mice treated with anti-mice CD122 antibody was (63.0 ± 12.2)% and (53.2 ± 16.3)%,respectively,which were dramatically higher than that in the mice treated with isotype control antibody (7.7 ± 3.6)% and (6.1 ± 2.4)%. Moreover,at 8 weeks after transplantation,human CD34⁺ cells appeared significantly in the recipients treated with anti-CD122 antibody. It is concluded that the anti-mouse CD122 antibody enhances the hematopoietic repopulating capacity of cord blood CD34⁺ cells in the NOD/SCID mice through decreasing the proportion of NK cells.

Interlaboratory evaluation of Hyalella azteca and Chironomus tentans short-term and long-term sediment toxicity tests

USGS Publications Warehouse

Norberg-King, T. J.; Sibley, P.K.; Burton, G.A.; Ingersoll, C.G.; Kemble, N.E.; Ireland, S.; Mount, D.R.; Rowland, C.D.

2006-01-01

Methods for assessing the long-term toxicity of sediments to Hyalella azteca and Chironomus tentans can significantly enhance the capacity to assess sublethal effects of contaminated sediments through multiple endpoints. Sublethal tests allow us to begin to understand the relationship between short-term and long-term effects for toxic sediments. We present an interlaboratory evaluation with long-term and 10-d tests using control and contaminated sediments in which we assess whether proposed and existing performance criteria (test acceptability criteria [TAC]) could be achieved. Laboratories became familiar with newly developed, long-term protocols by testing two control sediments in phase 1. In phase 2, the 10-d and long-term tests were examined with several sediments. Laboratories met the TACs, but results varied depending on the test organism, test duration, and endpoints. For the long-term tests in phase 1, 66 to 100% of the laboratories consistently met the TACs for survival, growth, or reproduction using H. azteca, and 70 to 100% of the laboratories met the TACs for survival and growth, emergence, reproduction, and hatchability using C. tentans. In phase 2, fewer laboratories participated in long-term tests: 71 to 88% of the laboratories met the TAC for H. azteca, whereas 50 to 67% met the TAC for C. tentans. In the 10-d tests with H. azteca, and C. tentans, 82 and 88% of the laboratories met the TAC for survival, respectively, and 80% met the TAC for C. tentans growth. For the 10-d and long-term tests, laboratories predicted similar toxicity. Overall, the interlaboratory evaluation showed good precision of the methods, appropriate endpoints were incorporated into the test protocols, and tests effectively predicted the toxicity of sediments.

A Novel Approach for Predicting Sublethal Effects of Toxicants to Aquatic Organisms

DTIC Science & Technology

1984-11-30

sublethal levels of copper. Overall, WSF P JP-4 appears to affect osmoregulation and liver function. These effects were much more pronounced in fish...i "-’p WOSR.TR. .0 8 Lfl SA NOVEL APPROACH FOR PREDICTING SUBLETHAL EFFECTS OF SI TOXICANTS TO AQUATIC ORGANISMS FINAL SCIENTIFIC REPORT GRANT AFOSR...alan A Novel Approach for �F 2312 AS JPredicting Sublethal Effects of Tbxicants to Aymtic- 12. PERIISONAL AUTHORIS) OrganISMS -Cairns, J.,-Jr

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

PubMed

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-term versus long-term, lethal versus sublethal, and median versus no response concentration ratios each contributed factors of about 2-3 to this overall ratio. The model for internal concentrations indicated that the ratio between the short-term and the long-term LC50 will be high for large species and high octanol-water partition ratios.

Chronic Sublethal Effects of San Francisco Bay Sediments on Nereis (Neanthes) arenaceodentata; Effect of Storage Time on Sediment Toxicity

DTIC Science & Technology

1994-04-01

Operations Program Chronic Sublethal Effects of San Francisco Bay Sediments on Nereis (Neanthes) arenaceodentata; Effect of Storage Time on Sediment...Dredging Miscellaneous Paper D-94-2 Operations Program April 1994 Chronic Sublethal Effects of San Francisco Bay Sediments on Nereis (Neanthes...tWatelrway EnD A2AIM a MI F~YRA • rI~WATIMA. •7 WATCH Moore, David W. Chronic sublethal effects of San Francisco Bay sediments on Nerels (Neanthes

Memory CD8+ T cells are sufficient to alleviate impaired host resistance to influenza A virus infection caused by neonatal oxygen supplementation.

PubMed

Giannandrea, Matthew; Yee, Min; O'Reilly, Michael A; Lawrence, B Paige

2012-09-01

Supplemental oxygen administered to preterm infants is an important clinical intervention, but it is associated with life-long changes in lung development and increased sensitivity to respiratory viral infections. The precise immunological changes caused by neonatal oxygen treatment remain poorly understood. We previously reported that adult mice exposed to supplemental oxygen as neonates display persistent pulmonary inflammation and enhanced mortality after a sublethal influenza A virus infection. These changes suggest that neonatal hyperoxia impairs the cytotoxic CD8(+) T cell response required to clear the virus. In this study, we show that although host resistance to several different strains of influenza A virus is reduced by neonatal hyperoxia, this treatment does not impair viral clearance, nor does it alter the magnitude of the virus-specific CD8(+) T cell response to primary infection. Moreover, memory T cells are sufficient to ameliorate the increased morbidity and mortality and alleviate the excessive lung damage observed in mice exposed to high oxygen levels as neonates, and we attribute this sufficiency principally to virus-specific memory CD8(+) T cells. Thus, we show that neonatal hyperoxia reduces host resistance to influenza virus infection without diminishing the function of cytotoxic T lymphocytes or the generation of virus-specific memory T cells and that CD8(+) memory T cells are sufficient to provide protection from negative consequences of this important life-saving intervention. Our findings suggest that vaccines that generate robust T cell memory may be efficacious at reducing the increased sensitivity to respiratory viral infections in people born prematurely.

Recovery of Sublethally Injured Bacteria Using Selective Agar Overlays.

ERIC Educational Resources Information Center

McKillip, John L.

2001-01-01

This experiment subjects bacteria in a food sample and an environmental sample to conditions of sublethal stress in order to assess the effectiveness of the agar overlay method to recover sublethally injured cells compared to direct plating onto the appropriate selective medium. (SAH)

Multiple sublethal chemicals negatively affect tadpoles of the green frog, Rana clamitans

USGS Publications Warehouse

Boone, Michelle D.; Bridges, Christine M.; Fairchild, James F.; Little, Edward E.

2005-01-01

Many habitats may be exposed to multiple chemical contaminants, particularly in agricultural areas where fertilizer and pesticide use are common; however, the singular and interactive effects of contaminants are not well understood. The objective of our study was to examine how realistic, sublethal environmental levels of ammonium nitrate fertilizer (0, 10, 20 mg/L and ammonium chloride control) and the common insecticide carbaryl (0 or 2.5 mg/L) individually and interactively affect the development, size, and survival of green frog (Rana clamitans) tadpoles. We reared tadpoles for 95 d in outdoor 1,000-L polyethylene ponds. We found that the combination of carbaryl and nitrate had a negative effect on development and mass of tadpoles compared to the positive effect that either contaminant had alone. Presence of carbaryl was generally associated with short-term increases in algal resources, including ponds exposed to both carbaryl and nitrate. However, with exposure to nitrate and carbaryl, tadpole mass and development were not positively affected as with one chemical stressor alone. The combination of these sublethal contaminants may reduce the ability of amphibians to benefit from food-rich environments or have metabolic costs. Our study demonstrates the importance of considering multiple stressors when evaluating population-level responses.

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

PubMed

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.

Use of an innovative T-tube maze assay and the proboscis extension response assay to assess sublethal effects of GM products and pesticides on learning capacity of the honey bee Apis mellifera L.

PubMed Central

Han, Peng; Lei, Chao-Liang; Cui, Jin-Jie; Desneux, Nicolas

2010-01-01

Transgenic Cry1Ac+CpTI cotton (CCRI41) is a promising cotton cultivar throughout China but side effects and especially sublethal effects of this transgenic cultivar on beneficial insects remain poorly studied. More specifically potential sublethal effects on behavioural traits of the honey bee Apis mellifera L. have not been formally assessed despite the importance of honey bees for pollination. The goal of our study was to assess potential effects of CCRI41 cotton pollen on visual and olfactory learning by honey bees. After a 7-day oral chronic exposure to honey mixed with either CCRI41 pollen, imidacloprid-treated conventional pollen (used as positive sublethal control) or conventional pollen (control), learning performance was evaluated by the classical proboscis extension reflex (PER) procedure as well as a T-tube maze test. The latter assay was designed as a new device to assess potential side effects of pesticides on visual associative learning of honey bees. These two procedures were complementary because the former focused on olfactory learning while the latter was involved in visual learning based on visual orientation ability. Oral exposure to CCRI41 pollen did not affect learning capacities of honey bees in both the T-tube maze and PER tests. However, exposure to imidacloprid resulted in reduced visual learning capacities in T-tube maze evaluation and decreased olfactory learning performances measured with PER. The implications of these results are discussed in terms of risks of transgenic CCRI41 cotton crops for honey bees. PMID:20872243

Tolerance development in Listeria monocytogenes-Escherichia coli dual-species biofilms after sublethal exposures to pronase-benzalkonium chloride combined treatments.

PubMed

Rodríguez-López, Pedro; Cabo, Marta López

2017-10-01

This study was designed to assess the effects that sublethal exposures to pronase (PRN) and benzalkonium chloride (BAC) combined treatments have on Listeria monocytogenes-Escherichia coli dual-species biofilms grown on stainless steel in terms of tolerance development (TD) to these compounds. Additionally, fluorescence microscopy was used to observe the changes of the biofilm structure. PRN-BAC exposure was carried out using three different approaches and TD was evaluated treating biofilms with a final 100 μg/ml PRN followed by 50 μg/ml BAC combined treatment. Results showed that exposure to PRN-BAC significantly decreased the number of adhered L. monocytogenes (P < 0.05), while E. coli counts remained generally unaltered. It was also demonstrated that the incorporation of recovery periods during sublethal exposures increased the tolerance of both species of the mixed biofilm to the final PRN-BAC treatment. Moreover, control biofilms became more resistant to PRN-BAC if longer incubation periods were used. Regardless of the treatment used, log reduction values were generally lower in L. monocytogenes compared to E. coli. Additionally, microscopy images showed an altered morphology produced by sublethal PRN-BAC in exposed L. monocytogenes-E. coli dual-species biofilms compared to control samples. Results also demonstrated that L. monocytogenes-E. coli dual-species biofilms are able to develop tolerance to PRN-BAC combined treatments depending on way they have been previously exposed. Moreover, they suggest that the generation of bacterial tolerance should be included as a parameter for sanitation procedures design. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sublethal Ciprofloxacin Treatment Leads to Rapid Development of High-Level Ciprofloxacin Resistance during Long-Term Experimental Evolution of Pseudomonas aeruginosa

PubMed Central

Jørgensen, Karin Meinike; Wassermann, Tina; Jensen, Peter Østrup; Hengzuang, Wang; Molin, Søren; Høiby, Niels

2013-01-01

The dynamics of occurrence and the genetic basis of ciprofloxacin resistance were studied in a long-term evolution experiment (940 generations) in wild-type, reference strain (PAO1) and hypermutable (PAOΔmutS and PAOMY-Mgm) P. aeruginosa populations continuously exposed to sub-MICs (1/4) of ciprofloxacin. A rapid occurrence of ciprofloxacin-resistant mutants (MIC of ≥12 μg/ml, representing 100 times the MIC of the original population) were observed in all ciprofloxacin-exposed lineages of PAOΔmutS and PAOMY-Mgm populations after 100 and 170 generations, respectively, and in one of the PAO1 lineages after 240 generations. The genetic basis of resistance was mutations in gyrA (C248T and G259T) and gyrB (C1397A). Cross-resistance to beta-lactam antibiotics was observed in the bacterial populations that evolved during exposure to sublethal concentrations of ciprofloxacin. Our study shows that mutants with high-level ciprofloxacin resistance are selected in P. aeruginosa bacterial populations exposed to sub-MICs of ciprofloxacin. This can have implications for the long-term persistence of resistant bacteria and spread of antibiotic resistance by exposure of commensal bacterial flora to low antibiotic concentrations. PMID:23774442

A Locomotor Deficit Induced by Sublethal Doses of Pyrethroid and Neonicotinoid Insecticides in the Honeybee Apis mellifera.

PubMed

Charreton, Mercédès; Decourtye, Axel; Henry, Mickaël; Rodet, Guy; Sandoz, Jean-Christophe; Charnet, Pierre; Collet, Claude

2015-01-01

The toxicity of pesticides used in agriculture towards non-targeted organisms and especially pollinators has recently drawn the attention from a broad scientific community. Increased honeybee mortality observed worldwide certainly contributes to this interest. The potential role of several neurotoxic insecticides in triggering or potentiating honeybee mortality was considered, in particular phenylpyrazoles and neonicotinoids, given that they are widely used and highly toxic for insects. Along with their ability to kill insects at lethal doses, they can compromise survival at sublethal doses by producing subtle deleterious effects. In this study, we compared the bee's locomotor ability, which is crucial for many tasks within the hive (e.g. cleaning brood cells, feeding larvae…), before and after an acute sublethal exposure to one insecticide belonging to the two insecticide classes, fipronil and thiamethoxam. Additionally, we examined the locomotor ability after exposure to pyrethroids, an older chemical insecticide class still widely used and known to be highly toxic to bees as well. Our study focused on young bees (day 1 after emergence) since (i) few studies are available on locomotion at this stage and (ii) in recent years, pesticides have been reported to accumulate in different hive matrices, where young bees undergo their early development. At sublethal doses (SLD48h, i.e. causing no mortality at 48 h), three pyrethroids, namely cypermethrin (2.5 ng/bee), tetramethrin (70 ng/bee), tau-fluvalinate (33 ng/bee) and the neonicotinoid thiamethoxam (3.8 ng/bee) caused a locomotor deficit in honeybees. While the SLD48h of fipronil (a phenylpyrazole, 0.5 ng/bee) had no measurable effect on locomotion, we observed high mortality several days after exposure, an effect that was not observed with the other insecticides. Although locomotor deficits observed in the sublethal range of pyrethroids and thiamethoxam would suggest deleterious effects in the field, the case of fipronil demonstrates that toxicity evaluation requires information on multiple endpoints (e.g. long term survival) to fully address pesticides risks for honeybees. Pyrethroid-induced locomotor deficits are discussed in light of recent advances regarding their mode of action on honeybee ion channels and current structure-function studies.

A Locomotor Deficit Induced by Sublethal Doses of Pyrethroid and Neonicotinoid Insecticides in the Honeybee Apis mellifera

PubMed Central

Charreton, Mercédès; Decourtye, Axel; Henry, Mickaël; Rodet, Guy; Sandoz, Jean-Christophe; Charnet, Pierre; Collet, Claude

2015-01-01

The toxicity of pesticides used in agriculture towards non-targeted organisms and especially pollinators has recently drawn the attention from a broad scientific community. Increased honeybee mortality observed worldwide certainly contributes to this interest. The potential role of several neurotoxic insecticides in triggering or potentiating honeybee mortality was considered, in particular phenylpyrazoles and neonicotinoids, given that they are widely used and highly toxic for insects. Along with their ability to kill insects at lethal doses, they can compromise survival at sublethal doses by producing subtle deleterious effects. In this study, we compared the bee’s locomotor ability, which is crucial for many tasks within the hive (e.g. cleaning brood cells, feeding larvae…), before and after an acute sublethal exposure to one insecticide belonging to the two insecticide classes, fipronil and thiamethoxam. Additionally, we examined the locomotor ability after exposure to pyrethroids, an older chemical insecticide class still widely used and known to be highly toxic to bees as well. Our study focused on young bees (day 1 after emergence) since (i) few studies are available on locomotion at this stage and (ii) in recent years, pesticides have been reported to accumulate in different hive matrices, where young bees undergo their early development. At sublethal doses (SLD48h, i.e. causing no mortality at 48h), three pyrethroids, namely cypermethrin (2.5 ng/bee), tetramethrin (70 ng/bee), tau-fluvalinate (33 ng/bee) and the neonicotinoid thiamethoxam (3.8 ng/bee) caused a locomotor deficit in honeybees. While the SLD48h of fipronil (a phenylpyrazole, 0.5 ng/bee) had no measurable effect on locomotion, we observed high mortality several days after exposure, an effect that was not observed with the other insecticides. Although locomotor deficits observed in the sublethal range of pyrethroids and thiamethoxam would suggest deleterious effects in the field, the case of fipronil demonstrates that toxicity evaluation requires information on multiple endpoints (e.g. long term survival) to fully address pesticides risks for honeybees. Pyrethroid-induced locomotor deficits are discussed in light of recent advances regarding their mode of action on honeybee ion channels and current structure-function studies. PMID:26659095

Sublethal effect of imidacloprid on Solenopsis invicta (Hymenoptera: Formicidae) feeding, digging, and foraging behavior

USDA-ARS?s Scientific Manuscript database

There is increasing evidence that exposure to neonicotinoid insecticides at sublethal levels impairs colonies of honeybee and other pollinators. Recently, it was found that sublethal contamination with neonicotinoids also affect growth and behavior of ants. In this study, we exposed red imported fi...

Measures of fish behavior as indicators of sublethal toxicosis during standard toxicity tests

USGS Publications Warehouse

Little, E.E.; DeLonay, A.J.

1996-01-01

Behavioral functions essential for growth and survival can be dramatically altered by sublethal exposure to toxicants. Measures of these behavioral responses are effective in detecting adverse effects of sublethal contaminant exposure. Behavioral responses of fishes can be qualitatively and quantitatively evaluated during routine toxicity tests. At selected intervals of exposure, qualitative evaluations are accomplished through direct observations, whereas video recordings are used for quantitative evaluations. Standardized procedures for behavioral evaluation are readily applicable to different fish species and provide rapid, sensitive, and ecologically relevant assessments of sublethal exposure. The methods are readily applied to standardized test protocols.

Lethal and sub-lethal effects from short-term exposure of Rhyzopertha dominica on wheat treated with Storicide II®

USDA-ARS?s Scientific Manuscript database

Hard red winter wheat was treated at 0 (untreated control), 25, 50, 75, and 100% of the label rate of the insecticide Storicide II®, which is chlorpyrifos-methyl and deltamethrin applied at label rates of 3 and 0.5 ppm, respectively. Paired male and female Rhyzopertha dominica F., the lesser grain b...

Recurrent sublethal warming reduces embryonic survival, inhibits juvenile growth, and alters species distribution projections under climate change.

PubMed

Carlo, Michael A; Riddell, Eric A; Levy, Ofir; Sears, Michael W

2018-01-01

The capacity to tolerate climate change often varies across ontogeny in organisms with complex life cycles. Recently developed species distribution models incorporate traits across life stages; however, these life-cycle models primarily evaluate effects of lethal change. Here, we examine impacts of recurrent sublethal warming on development and survival in ecological projections of climate change. We reared lizard embryos in the laboratory under temperature cycles that simulated contemporary conditions and warming scenarios. We also artificially warmed natural nests to mimic laboratory treatments. In both cases, recurrent sublethal warming decreased embryonic survival and hatchling sizes. Incorporating survivorship results into a mechanistic species distribution model reduced annual survival by up to 24% compared to models that did not incorporate sublethal warming. Contrary to models without sublethal effects, our model suggests that modest increases in developmental temperatures influence species ranges due to effects on survivorship. © 2017 John Wiley & Sons Ltd/CNRS.

Chronic sublethal stress causes bee colony failure.

PubMed

Bryden, John; Gill, Richard J; Mitton, Robert A A; Raine, Nigel E; Jansen, Vincent A A

2013-12-01

Current bee population declines and colony failures are well documented yet poorly understood and no single factor has been identified as a leading cause. The evidence is equivocal and puzzling: for instance, many pathogens and parasites can be found in both failing and surviving colonies and field pesticide exposure is typically sublethal. Here, we investigate how these results can be due to sublethal stress impairing colony function. We mathematically modelled stress on individual bees which impairs colony function and found how positive density dependence can cause multiple dynamic outcomes: some colonies fail while others thrive. We then exposed bumblebee colonies to sublethal levels of a neonicotinoid pesticide. The dynamics of colony failure, which we observed, were most accurately described by our model. We argue that our model can explain the enigmatic aspects of bee colony failures, highlighting an important role for sublethal stress in colony declines. © 2013 The Authors. Ecology Letters published by John Wiley & Sons Ltd and CNRS.

Chronic sublethal stress causes bee colony failure

PubMed Central

Bryden, John; Gill, Richard J; Mitton, Robert A A; Raine, Nigel E; Jansen, Vincent A A; Hodgson, David

2013-01-01

Current bee population declines and colony failures are well documented yet poorly understood and no single factor has been identified as a leading cause. The evidence is equivocal and puzzling: for instance, many pathogens and parasites can be found in both failing and surviving colonies and field pesticide exposure is typically sublethal. Here, we investigate how these results can be due to sublethal stress impairing colony function. We mathematically modelled stress on individual bees which impairs colony function and found how positive density dependence can cause multiple dynamic outcomes: some colonies fail while others thrive. We then exposed bumblebee colonies to sublethal levels of a neonicotinoid pesticide. The dynamics of colony failure, which we observed, were most accurately described by our model. We argue that our model can explain the enigmatic aspects of bee colony failures, highlighting an important role for sublethal stress in colony declines. PMID:24112478

Biosynthetic requirements for the repair of sublethally injured Saccharomyces cerevisiae cells after pulsed electric fields.

PubMed

Somolinos, M; García, D; Condón, S; Mañas, P; Pagán, R

2008-07-01

The aim was to evaluate the biosynthetic requirements for the repair of sublethal membrane damages in Saccharomyces cerevisiae cells after exposure to pulsed electric fields (PEF). The partial loss of the integrity and functionality of the cytoplasmic membrane was assessed by adding sodium chloride to the recovery medium. More than 2 log(10) cycles of survivors were sublethally injured after PEF. Repair of sublethal membrane damages occurred when survivors to PEF were incubated in Sabouraud Broth for 4 h at room temperature. The addition of inhibitors, such as chloramphenicol, rifampicin, 5-fluorocytosine, nalidixic acid, cycloheximide, cerulenin, miconazol and sodium azide to the liquid repair medium showed that the repair of PEF-injured cells required energy and protein synthesis. The extent of the sublethal damages was greater in PEF-treated cells at pH 4.0 than at pH 7.0. This work confirms that membrane damage is an important event in the PEF-inactivation of yeast. The mechanism of yeast inactivation by PEF seems to differ from that of bacteria, as the repair of sublethal damages requires protein synthesis. Knowledge about the damages inflicted by PEF leads to a better description of the mechanism of yeast inactivation.

Impact of sublethal exposure to a pyrethroid-neonicotinoid insecticide on mating, fecundity and development in the bed bug Cimex lectularius L. (Hemiptera: Cimicidae).

PubMed

Crawley, Sydney E; Gordon, Jennifer R; Kowles, Katelyn A; Potter, Michael F; Haynes, Kenneth F

2017-01-01

Sublethal exposure to an insecticide may alter insect feeding, mating, oviposition, fecundity, development, and many other life history parameters. Such effects may have population-level consequences that are not apparent in traditional dose-mortality evaluations. Earlier, we found that a routinely used combination insecticide that includes a pyrethroid and a neonicotinoid (Temprid® SC) had deleterious effects on multiple bed bug (Cimex lectularius, L.) behaviors. Here, we demonstrate that sublethal exposure impacts physiology and reproduction as well. We report that sublethal exposure to Temprid SC has variable aberrant effects on bed bugs depending on the strain, including: a reduction in male mating success and delayed oviposition by females. However, after sublethal exposure, egg hatch rate consistently declined in every strain tested, anywhere from 34%-73%. Conversely, impact on fifth instar eclosion time was not significant. While the strains that we tested varied in their respective magnitude of sublethal effects, taken together, these effects could reduce bed bug population growth. These changes in bed bug behavior and fecundity could lead to improved efficacy of Temprid SC in the field, but recovery of impacted bugs must be considered in future studies. Sublethal effects should not be overlooked when evaluating insecticide efficacy, as it is likely that other products may also have indirect effects on population dynamics that could either aid or inhibit successful management of pest populations.

Sub-lethal glyphosate exposure alters flowering phenology and causes transient male-sterility in Brassica spp

PubMed Central

2014-01-01

Background Herbicide resistance in weedy plant populations can develop through different mechanisms such as gene flow of herbicide resistance transgenes from crop species into compatible weedy species or by natural evolution of herbicide resistance or tolerance following selection pressure. Results from our previous studies suggest that sub-lethal levels of the herbicide glyphosate can alter the pattern of gene flow between glyphosate resistant Canola®, Brassica napus, and glyphosate sensitive varieties of B. napus and B. rapa. The objectives of this study were to examine the phenological and developmental changes that occur in Brassica crop and weed species following sub-lethal doses of the herbicides glyphosate and glufosinate. We examined several vegetative and reproductive traits of potted plants under greenhouse conditions, treated with sub-lethal herbicide sprays. Results Our results indicate that exposure of Brassica spp. to a sub-lethal dose of glyphosate results in altering flowering phenology and reproductive function. Flowering of all sensitive species was significantly delayed and reproductive function, specifically male fertility, was suppressed. Higher dosage levels typically contributed to an increase in the magnitude of phenotypic changes. Conclusions These results demonstrate that Brassica spp. plants that are exposed to sub-lethal doses of glyphosate could be subject to very different pollination patterns and an altered pattern of gene flow that would result from changes in the overlap of flowering phenology between species. Implications include the potential for increased glyphosate resistance evolution and spread in weedy communities exposed to sub-lethal glyphosate. PMID:24655547

Sub-lethal glyphosate exposure alters flowering phenology and causes transient male-sterility in Brassica spp.

PubMed

Londo, Jason Paul; McKinney, John; Schwartz, Matthew; Bollman, Mike; Sagers, Cynthia; Watrud, Lidia

2014-03-21

Herbicide resistance in weedy plant populations can develop through different mechanisms such as gene flow of herbicide resistance transgenes from crop species into compatible weedy species or by natural evolution of herbicide resistance or tolerance following selection pressure. Results from our previous studies suggest that sub-lethal levels of the herbicide glyphosate can alter the pattern of gene flow between glyphosate resistant Canola®, Brassica napus, and glyphosate sensitive varieties of B. napus and B. rapa. The objectives of this study were to examine the phenological and developmental changes that occur in Brassica crop and weed species following sub-lethal doses of the herbicides glyphosate and glufosinate. We examined several vegetative and reproductive traits of potted plants under greenhouse conditions, treated with sub-lethal herbicide sprays. Our results indicate that exposure of Brassica spp. to a sub-lethal dose of glyphosate results in altering flowering phenology and reproductive function. Flowering of all sensitive species was significantly delayed and reproductive function, specifically male fertility, was suppressed. Higher dosage levels typically contributed to an increase in the magnitude of phenotypic changes. These results demonstrate that Brassica spp. plants that are exposed to sub-lethal doses of glyphosate could be subject to very different pollination patterns and an altered pattern of gene flow that would result from changes in the overlap of flowering phenology between species. Implications include the potential for increased glyphosate resistance evolution and spread in weedy communities exposed to sub-lethal glyphosate.

Tissue-specific accumulation of cadmium in subcellular compartments of eastern oysters Crassostrea virginica Gmelin (Bivalvia: Ostreidae).

PubMed

Sokolova, I M; Ringwood, A H; Johnson, C

2005-09-10

Cadmium distribution was studied in different subcellular fractions of gill and hepatopancreas tissues of eastern oysters Crassostrea virginica. Oysters were exposed for up to 21 days to low sublethal Cd concentrations (25 microg L(-1)). Gill and hepatopancreas tissues were sampled and divided into organelle fractions and cytosol by differential centrifugation. Organelle content of different fractions was verified by activities of marker enzymes, citrate synthase and acid phosphatase for mitochondria and lysosomes, respectively. In both tissue types, there was a significant accumulation of cadmium in cytosol reaching 230-350 ng mg(-1) protein. Among organelles, mitochondria were the main target for Cd bioaccumulation in gills (250-300 ng mg(-1) protein), whereas in hepatopancreas tissues, the highest cadmium accumulation occurred in lysosomes (90-94 ng mg(-1) protein). Although 75-83% of total cadmium burden was associated with the cytosol reflecting high volume fraction of this compartment, Cd concentrations in organelle fractions reached levels that could cause dysfunction of mitochondria and lysosomes. Organ- and organelle-specific patterns of cadmium bioaccumulation support our previous in vivo studies, which showed adverse effects of cadmium exposures on mitochondrial oxidation in gills and on the lysosomal system of hepatopancreas. This may have important implications for the development of biomarkers of effect for heavy metals and for understanding the mechanisms of toxic effects of metals.

Modeling Population and Ecosystem Response to Sublethal Toxicant Exposure

DTIC Science & Technology

2000-09-30

Modeling Population and Ecosystem Response to Sublethal Toxicant Exposure Principal Investigator: Roger M. Nisbet Department of Ecology, Evolution...DATES COVERED 00-00-2000 to 00-00-2000 4. TITLE AND SUBTITLE Modeling Population and Ecosystem Response to Sublethal Toxicant Exposure 5a...those of real populations. We have also investigated how toxicants may affect the stability of the system. If the toxicant effect is primarily an

Long-term hematopoietic stem cell damage in a murine model of the hematopoietic syndrome of the acute radiation syndrome.

PubMed

Chua, Hui Lin; Plett, P Artur; Sampson, Carol H; Joshi, Mandar; Tabbey, Rebeka; Katz, Barry P; MacVittie, Thomas J; Orschell, Christie M

2012-10-01

Residual bone marrow damage (RBMD) persists for years following exposure to radiation and is believed to be due to decreased self-renewal potential of radiation-damaged hematopoietic stem cells (HSC). Current literature has examined primarily sublethal doses of radiation and time points within a few months of exposure. In this study, the authors examined RBMD in mice surviving lethal doses of total body ionizing irradiation (TBI) in a murine model of the Hematopoietic Syndrome of the Acute Radiation Syndrome (H-ARS). Survivors were analyzed at various time points up to 19 mo post-TBI for hematopoietic function. The competitive bone marrow (BM) repopulating potential of 150 purified c-Kit+ Sca-1+ lineage- CD150+ cells (KSLCD150+) remained severely deficient throughout the study compared to KSLCD150+ cells from non-TBI age-matched controls. The minimal engraftment from these TBI HSCs is predominantly myeloid, with minimal production of lymphocytes both in vitro and in vivo. All classes of blood cells as well as BM cellularity were significantly decreased in TBI mice, especially at later time points as mice aged. Primitive BM hematopoietic cells (KSLCD150+) displayed significantly increased cell cycling in TBI mice at all time points, which may be a physiological attempt to maintain HSC numbers in the post-irradiation state. Taken together, these data suggest that the increased cycling among primitive hematopoietic cells in survivors of lethal radiation may contribute to long-term HSC exhaustion and subsequent RBMD, exacerbated by the added insult of aging at later time points.

Modeling Population and Ecosystem Response to Sublethal Toxicant Exposure

DTIC Science & Technology

2001-09-30

mutualism utilized modified Lotka - Volterra (L-V) competition equations in which the sign of the interspecific interaction term was changed from...within complex communities and ecosystems. Prior to the current award, the PIs formulated and tested general dynamic energy budget models...Nisbet, 1998; chapter 7) make a convincing case that ecosystems do truly have dynamics that can be described by relatively simple, general , models

Effect of sublethal heat treatment on the later stage of germination-to-outgrowth of Clostridium perfringens spores.

PubMed

Sakanoue, Hideyo; Yasugi, Mayo; Miyake, Masami

2018-05-04

Sublethal heating of spores has long been known to stimulate or activate germination, but the underlying mechanisms are not yet fully understood. In this study, we visualized the entire germination-to-outgrowth process of spores from an anaerobic sporeformer, C. perfringens, at single-cell resolution. Quantitative analysis revealed that sublethal heating significantly reduced the time from completion of germination to the beginning of the first cell division. The results indicate that sublethal heating of C. perfringens spores not only sensitizes the responsiveness of germinant receptors but also directly or indirectly facilitates multiple steps during the bacterial regrowth process. © 2018 The Societies and John Wiley & Sons Australia, Ltd.

Cyclic AMP-Elevating Capacity of Adenylate Cyclase Toxin-Hemolysin Is Sufficient for Lung Infection but Not for Full Virulence of Bordetella pertussis

PubMed Central

Skopova, Karolina; Tomalova, Barbora; Kanchev, Ivan; Rossmann, Pavel; Svedova, Martina; Adkins, Irena; Bibova, Ilona; Tomala, Jakub; Masin, Jiri; Guiso, Nicole; Osicka, Radim; Sedlacek, Radislav; Kovar, Marek

2017-01-01

ABSTRACT The adenylate cyclase toxin-hemolysin (CyaA, ACT, or AC-Hly) of Bordetella pertussis targets phagocytic cells expressing the complement receptor 3 (CR3, Mac-1, αMβ2 integrin, or CD11b/CD18). CyaA delivers into cells an N-terminal adenylyl cyclase (AC) enzyme domain that is activated by cytosolic calmodulin and catalyzes unregulated conversion of cellular ATP into cyclic AMP (cAMP), a key second messenger subverting bactericidal activities of phagocytes. In parallel, the hemolysin (Hly) moiety of CyaA forms cation-selective hemolytic pores that permeabilize target cell membranes. We constructed the first B. pertussis mutant secreting a CyaA toxin having an intact capacity to deliver the AC enzyme into CD11b-expressing (CD11b+) host phagocytes but impaired in formation of cell-permeabilizing pores and defective in cAMP elevation in CD11b− cells. The nonhemolytic AC+ Hly− bacteria inhibited the antigen-presenting capacities of coincubated mouse dendritic cells in vitro and skewed their Toll-like receptor (TLR)-triggered maturation toward a tolerogenic phenotype. The AC+ Hly− mutant also infected mouse lungs as efficiently as the parental AC+ Hly+ strain. Hence, elevation of cAMP in CD11b− cells and/or the pore-forming capacity of CyaA were not required for infection of mouse airways. The latter activities were, however, involved in bacterial penetration across the epithelial layer, enhanced neutrophil influx into lung parenchyma during sublethal infections, and the exacerbated lung pathology and lethality of B. pertussis infections at higher inoculation doses (>107 CFU/mouse). The pore-forming activity of CyaA further synergized with the cAMP-elevating activity in downregulation of major histocompatibility complex class II (MHC-II) molecules on infiltrating myeloid cells, likely contributing to immune subversion of host defenses by the whooping cough agent. PMID:28396322

Listeriosis downregulates hepatic cytochrome P450 enzymes in sublethal murine infection.

PubMed

Kummer, Anne; Nishanth, Gopala; Koschel, Josephin; Klawonn, Frank; Schlüter, Dirk; Jänsch, Lothar

2016-10-01

Listeria monocytogenes (Lm) can cross the intestinal barrier in humans and then disseminates into different organs. Invasion of the liver occurs even in sublethal infections, however, knowledge of affected physiological processes is scarce. This study employed a sublethal murine infection model to investigate liver responses systematically by proteomics. Liver samples from three stages of the sublethal infection covering the initial invasion, the peak of infection, and the clearance phase (1, 3, 9 days postinoculation) were analyzed in comparison to samples from noninfected mice. Apart from flow cytometry and RT-PCRs for immune status control, liver responses were analyzed by quantitative peptide sequencing (HPLC-Orbitrap Fusion) using 4-plex iTRAQ-labeling. Accurate MS characterized about 3600 proteins and statistics revealed 15% of the hepatic proteome as regulated. Immunological data as well as protein regulation dynamics strongly indicate stage-specific hepatic responses in sublethal infections. Most notably, this study detected a comprehensive deregulation of drug metabolizing enzymes at all stages, including 25 components of the cytochrome P450 system. Sublethal Lm infection deregulates hepatic drug metabolizing pathways. This finding indicates the need to monitor drug administration along Lm infections, especially in all patients needing constant medication. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lethal and sub-lethal effects of spinosad on bumble bees (Bombus impatiens Cresson).

PubMed

Morandin, Lora A; Winston, Mark L; Franklin, Michelle T; Abbott, Virginia A

2005-07-01

Recent developments of new families of pesticides and growing awareness of the importance of wild pollinators for crop pollination have stimulated interest in potential effects of novel pesticides on wild bees. Yet pesticide toxicity studies on wild bees remain rare, and few studies have included long-term monitoring of bumble bee colonies or testing of foraging ability after pesticide exposure. Larval bees feeding on exogenous pollen and exposed to pesticides during development may result in lethal or sub-lethal effects during the adult stage. We tested the effects of a naturally derived biopesticide, spinosad, on bumble bee (Bombus impatiens Cresson) colony health, including adult mortality, brood development, weights of emerging bees and foraging efficiency of adults that underwent larval development during exposure to spinosad. We monitored colonies from an early stage, over a 10-week period, and fed spinosad to colonies in pollen at four levels: control, 0.2, 0.8 and 8.0 mg kg(-1), during weeks 2 through 5 of the experiment. At concentrations that bees would likely encounter in pollen in the wild (0.2-0.8 mg kg(-1)) we detected minimal negative effects to bumble bee colonies. Brood and adult mortality was high at 8.0 mg kg(-1) spinosad, about twice the level that bees would be exposed to in a 'worst case' field scenario, resulting in colony death two to four weeks after initial pesticide exposure. At more realistic concentrations there were potentially important sub-lethal effects. Adult worker bees exposed to spinosad during larval development at 0.8 mg kg(-1) were slower foragers on artificial complex flower arrays than bees from low or no spinosad treated colonies. Inclusion of similar sub-lethal assays to detect effects of pesticides on pollinators would aid in development of environmentally responsible pest management strategies. Copyright 2005 Society of Chemical Industry

The Oslo definitions for coeliac disease and related terms

PubMed Central

Ludvigsson, Jonas F; Leffler, Daniel A; Bai, Julio; Biagi, Federico; Fasano, Alessio; Green, Peter HR; Hadjivassiliou, Marios; Kaukinen, Katri; Kelly, Ciaran; Leonard, Jonathan N; Lundin, Knut E; Murray, Joseph A; Sanders, David S; Walker, Marjorie M; Zingone, Fabiana; Ciacci, Carolina

2012-01-01

Background The literature suggests a lack of consensus on the use of terms related to coeliac disease (CD) and gluten. Methods A multi-disciplinary task force of 16 physicians from 7 countries used the electronic database PubMed to review the literature with regards to CD-related terms up to January 2011. Teams of physicians then suggested a definition for each term, followed by feedback of these definitions through a web survey on definitions, discussions during a meeting in Oslo, and phone conferences. We evaluated the following terms (in alphabetical order): Coeliac disease and the following descriptors of CD: asymptomatic, atypical, classical, latent, non-classical, overt, paediatric classical, potential, refractory, silent, subclinical, symptomatic, typical, CD serology, CD autoimmunity, genetically at risk of CD, dermatitis herpetiformis, gluten, gluten ataxia, gluten intolerance, gluten sensitivity, and gliadin-specific antibodies. Results CD was defined as “a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals”. Classical CD was defined as “CD presenting with signs and symptoms of malabsorption. Diarrhoea, steatorrhoea, weight loss or growth failure is required.” We suggest that “gluten-related disorders” is the umbrella term for all diseases triggered by gluten and that the term gluten intolerance is not to be used. Other definitions are presented in the paper. Conclusion This paper presents the Oslo definitions for CD-related terms. PMID:22345659

The SOS response increases bacterial fitness, but not evolvability, under a sublethal dose of antibiotic.

PubMed

Torres-Barceló, Clara; Kojadinovic, Mila; Moxon, Richard; MacLean, R Craig

2015-10-07

Exposure to antibiotics induces the expression of mutagenic bacterial stress-response pathways, but the evolutionary benefits of these responses remain unclear. One possibility is that stress-response pathways provide a short-term advantage by protecting bacteria against the toxic effects of antibiotics. Second, it is possible that stress-induced mutagenesis provides a long-term advantage by accelerating the evolution of resistance. Here, we directly measure the contribution of the Pseudomonas aeruginosa SOS pathway to bacterial fitness and evolvability in the presence of sublethal doses of ciprofloxacin. Using short-term competition experiments, we demonstrate that the SOS pathway increases competitive fitness in the presence of ciprofloxacin. Continued exposure to ciprofloxacin results in the rapid evolution of increased fitness and antibiotic resistance, but we find no evidence that SOS-induced mutagenesis accelerates the rate of adaptation to ciprofloxacin during a 200 generation selection experiment. Intriguingly, we find that the expression of the SOS pathway decreases during adaptation to ciprofloxacin, and this helps to explain why this pathway does not increase long-term evolvability. Furthermore, we argue that the SOS pathway fails to accelerate adaptation to ciprofloxacin because the modest increase in the mutation rate associated with SOS mutagenesis is offset by a decrease in the effective strength of selection for increased resistance at a population level. Our findings suggest that the primary evolutionary benefit of the SOS response is to increase bacterial competitive ability, and that stress-induced mutagenesis is an unwanted side effect, and not a selected attribute, of this pathway. © 2015 The Authors.

The SOS response increases bacterial fitness, but not evolvability, under a sublethal dose of antibiotic

PubMed Central

Torres-Barceló, Clara; Kojadinovic, Mila; Moxon, Richard; MacLean, R. Craig

2015-01-01

Exposure to antibiotics induces the expression of mutagenic bacterial stress–response pathways, but the evolutionary benefits of these responses remain unclear. One possibility is that stress–response pathways provide a short-term advantage by protecting bacteria against the toxic effects of antibiotics. Second, it is possible that stress-induced mutagenesis provides a long-term advantage by accelerating the evolution of resistance. Here, we directly measure the contribution of the Pseudomonas aeruginosa SOS pathway to bacterial fitness and evolvability in the presence of sublethal doses of ciprofloxacin. Using short-term competition experiments, we demonstrate that the SOS pathway increases competitive fitness in the presence of ciprofloxacin. Continued exposure to ciprofloxacin results in the rapid evolution of increased fitness and antibiotic resistance, but we find no evidence that SOS-induced mutagenesis accelerates the rate of adaptation to ciprofloxacin during a 200 generation selection experiment. Intriguingly, we find that the expression of the SOS pathway decreases during adaptation to ciprofloxacin, and this helps to explain why this pathway does not increase long-term evolvability. Furthermore, we argue that the SOS pathway fails to accelerate adaptation to ciprofloxacin because the modest increase in the mutation rate associated with SOS mutagenesis is offset by a decrease in the effective strength of selection for increased resistance at a population level. Our findings suggest that the primary evolutionary benefit of the SOS response is to increase bacterial competitive ability, and that stress-induced mutagenesis is an unwanted side effect, and not a selected attribute, of this pathway. PMID:26446807

Behavioural and biochemical responses to metals tested alone or in mixture (Cd-Cu-Ni-Pb-Zn) in Gammarus fossarum: From a multi-biomarker approach to modelling metal mixture toxicity.

PubMed

Lebrun, Jérémie D; Uher, Emmanuelle; Fechner, Lise C

2017-12-01

Metals are usually present as mixtures at low concentrations in aquatic ecosystems. However, the toxicity and sub-lethal effects of metal mixtures on organisms are still poorly addressed in environmental risk assessment. Here we investigated the biochemical and behavioural responses of Gammarus fossarum to Cu, Cd, Ni, Pb and Zn tested individually or in mixture (M2X) at concentrations twice the levels of environmental quality standards (EQSs) from the European Water Framework Directive. The same metal mixture was also tested with concentrations equivalent to EQSs (M1X), thus in a regulatory context, as EQSs are proposed to protect aquatic biota. For each exposure condition, mortality, locomotion, respiration and enzymatic activities involved in digestive metabolism and moult were monitored over a 120h exposure period. Multi-metric variations were summarized by the integrated biomarker response index (IBR). Mono-metallic exposures shed light on biological alterations occurring at environmental exposure levels in gammarids and depending on the considered metal and gender. As regards mixtures, biomarkers were altered for both M2X and M1X. However, no additive or synergistic effect of metals was observed comparing to mono-metallic exposures. Indeed, bioaccumulation data highlighted competitive interactions between metals in M2X, decreasing subsequently their internalisation and toxicity. IBR values indicated that the health of gammarids was more impacted by M1X than M2X, because of reduced competitions and enhanced uptakes of metals for the mixture at lower, EQS-like concentrations. Models using bioconcentration data obtained from mono-metallic exposures generated successful predictions of global toxicity both for M1X and M2X. We conclude that sub-lethal effects of mixtures identified by the multi-biomarker approach can lead to disturbances in population dynamics of gammarids. Although IBR-based models offer promising lines of enquiry to predict metal mixture toxicity, further studies are needed to confirm their predictive quality on larger ranges of metallic combinations before their use in field conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

Long-term erythropoietic repopulating ability of old, young, and fetal stem cells.

PubMed

Harrison, D E

1983-05-01

It is possible that erythropoietic stem cells do not age. This would mean that stem cells from old donors can function as well as those from young or fetal donors. The competitive repopulation assay has been used to test long-term stem cell function by directly comparing how well competing stem cells repopulate a recipient and produce differentiated cell types. C57BL/6J (B6) mice were used as donors, while recipients and competitors were WBB6F1 hybrids with genetically distinguishable hemoglobin. Lethally irradiated young WBB6F1 recipients were given a mixture of 2.5 X 10(6) cells from B6 old marrow, young marrow, or fetal liver donors; each recipient also received a standard dose of 1 X 10(6) marrow cells from a pool of young WBB6F1 competitors. Surprisingly, the old marrow cells competed the best in repopulating the recipients. This pattern was maintained even after recovery from sublethal irradiation, a treatment that severely stresses stem cells. This stress was demonstrated when sublethal irradiation caused a 20-fold decline in repopulating ability measured using hemoglobin markers, and a 3- to 7-fold decline using chromosome markers. Stem cells from old marrow competed better than young or fetal cells in similar experiments using immunologically crippled recipients or using unirradiated W/Wv recipients that are immunologically intact. In both types of recipients, the advantage of old marrow cells again persisted after recovery from sublethal irradiation. Other genotypes were tested, and marrow cells from old B6CBAF1 donors competed better than those from young donors of that genotype. However, marrow cells from young CBA donors completed better than those from old CBA donors. These results support the hypothesis that stem cells do not age, and suggest that regulatory changes with age promote rapid stem cell repopulation in B6 and B6CBAF1 mice, but inhibit it in CBA mice.

Long-term evaluation of lethal and sublethal toxicity of industrial effluents using Daphnia magna and Moina macrocopa.

PubMed

Yi, Xianliang; Kang, Sung-Wook; Jung, Jinho

2010-06-15

Acute toxicity and feeding rate inhibition of effluent from a wastewater treatment plant and its adjacent stream water on Daphnia magna and Moina macrocopa were comparatively studied. The acute toxicity of the final effluent (FE) fluctuated greatly over the sampling period from January to August 2009. Toxicity identification results of the FE in July 2009 showed that Cu originating from the Fenton's reagent was likely a key toxicant. In addition, the feeding rate of both species was still inhibited by the FEs in which acute toxicity was not observed. These findings indicate that the feeding response would be a useful tool for monitoring sublethal effects of industrial effluents. For the acute toxicity test, M. macrocopa was more sensitive than D. magna, but the opposite result was true in the case of the feeding rate inhibition. These suggest that different species have different sensitivities to toxic chemicals and to the test methods. Copyright 2010 Elsevier B.V. All rights reserved.

Physiological effects of toxic substances on wildlife species

USGS Publications Warehouse

Haseltine, S.D.; Kacmar, Peter; Legath, J.

1983-01-01

Study of the physiological effects of contaminants on wildlife species has expanded as more sophisticated medical techniques are adapted to wildlife and as the mode of action of new classes of pesticides increase the number of organ systems which may be sublethally or lethally impacted. This paper summarizes some of the latest data published on toxicant affects on organ systems of warm-blooded vertebrates. Reporting on effects with enzyme systems concentrates on cholinesterase in blood and plasma after sublethal and lethal exposure to organophosphate end carbamate pesticides, but also covers, recent work with Na+, k+-ATPases, AST, AAT, and AL.AD. A discussion of recent work on hormones, biogenlc amines, and other compounds which indicate alteration of specific organ systems, is followed by examples of histopathological lesions associated both pathognomically and non-specifically with widely-used and/or severely toxic contaminants. All these specific effects and lesions are then discussed in terms of their potential for use diagnostically in field problems and their practical and possible impact on wildlife populations.

Quorum Sensing: A transcriptional Regulatory System Involved in the Pathogenicity of Burkholderia mallei

DTIC Science & Technology

2004-11-01

contributes to the pathogenicity of B. mallei in vivo. 15. SUBJECT TERMS Burkholderia mallei , glanders , pseudomallei, quorum sensing, transcription...and D. M. Waag. 2000. Mouse model of sublethal and lethal intraperitoneal glanders ( Burkholderia mallei ). Vet. Pathol. 37:626–636. 10. Fuqua, C., M...sequence typing and evolutionary relationships among the causative agents of melioidosis and glanders , Burk- holderia pseudomallei and Burkholderia mallei

Induction of high tolerance to artemisinin by sub-lethal administration: A new in vitro model of P. falciparum.

PubMed

De Lucia, Serena; Tsamesidis, Ioannis; Pau, Maria Carmina; Kesely, Kristina R; Pantaleo, Antonella; Turrini, Francesco

2018-01-01

Artemisinin resistance is a major threat to malaria control efforts. Resistance is characterized by an increase in the Plasmodium falciparum parasite clearance half-life following treatment with artemisinin-based combination therapies (ACTs) and an increase in the percentage of surviving parasites. The remarkably short blood half-life of artemisinin derivatives may contribute to drug-resistance, possibly through factors including sub-lethal plasma concentrations and inadequate exposure. Here we selected for a new strain of artemisinin resistant parasites, termed the artemisinin resistant strain 1 (ARS1), by treating P. falciparum Palo Alto (PA) cultures with sub-lethal concentrations of dihydroartemisinin (DHA). The resistance phenotype was maintained for over 1 year through monthly maintenance treatments with low doses of 2.5 nM DHA. There was a moderate increase in the DHA IC50 in ARS1 when compared with parental strain PA after 72 h of drug exposure (from 0.68 nM to 2 nM DHA). In addition, ARS1 survived treatment physiologically relevant DHA concentrations (700 nM) observed in patients. Furthermore, we confirmed a lack of cross-resistance against a panel of antimalarials commonly used as partner drugs in ACTs. Finally, ARS1 did not contain Pfk13 propeller domain mutations associated with ART resistance in the Greater Mekong Region. With a stable growth rate, ARS1 represents a valuable tool for the development of new antimalarial compounds and studies to further elucidate the mechanisms of ART resistance.

Effect of methylparaben in Artemia franciscana.

PubMed

Comeche, Amparo; Martín-Villamil, María; Picó, Yolanda; Varó, Inma

2017-09-01

In this study, the toxicity of methylparaben (MeP) an emerging contaminant, was analysed in the sexual species Artemia franciscana, due to its presence in coastal areas and marine saltworks in the Mediterranean region. The acute toxicity (24h-LC 50 ) of MeP in nauplii was tested and its chronic effect (9days) evaluated by measuring survival and growth under two sublethal concentrations (0.0085 and 0.017mg/L). Also, the effect on several key enzymes involved in: antioxidant defences (catalase (CAT) and gluthathion-S-transferase (GST)), neural activity (cholinesterase (ChE)) and xenobiotic biotransformation (carboxylesterase (CbE), was assessed after 48h under sublethal exposure. The results of acute exposure indicate that MeP is harmful to A. franciscana (24h-LC 50 =36.7mg/L). MeP causes a decrease in CAT activity after 48h exposure to both concentration tested, that points out at the oxidative stress effect of MeP in A. franciscana. However, no significant effect on ChE, CbE and GST activities was found. In addition, MeP does not affect survival and growth in chronic exposure at the sublethal concentrations tested. The results of this study indicate that MeP is not a threat for A. franciscana under the experimental conditions used. Additional studies should be done considering long-term exposure and reproduction studies to analyse the potential risk of MeP as emerging contaminant in marine and hypersaline environments. Published by Elsevier Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giggleman, M.A.; Fitzpatrick, L.C.; Goven, A.J.

Phagocytosis, a host-defense mechanism phylogenetically conserved throughout the animal kingdom, by earthworm (Lumbricus terrestris) coelomocytes has potential as a surrogate for vertebrates to be used as an environmentally acceptable endpoint to assess sublethal immunotoxic risks of contaminated soils to environmental (eg. higher wildlife) and public health. Coelomocytes can be exposed in vivo to complex contaminated parent soils by placing earthworms in situ at hazardous waste sites (HWS) or into soil samples and their dilutions with artificial soil (AS) in the laboratory, or in vitro to soil extracts and their fractionations. Here the authors report on phagocytosis by coelomocytes in earthwormsmore » exposed to pentachlorophenol (PCP) contaminated soils from a wood treatment HWS, PCP-spiked AS and PCP treated filter paper (FP). HWS soil was diluted to 25% with AS to a sublethal concentration (ca. 125 mg kg{sup {minus}1}) and earthworms exposed for 14d at 10 C under light conditions. AS was spiked at ca. 125 mg kg{sup {minus}1} PCP and earthworms were similarly exposed. Controls for both consisted of earthworms exposed to 100% AS. Earthworms were exposed to FP treated with a sublethal PCP concentration (15 {micro}g cm{sup {minus}2}) at 10 C under dark conditions for 96H. Controls were similarly exposed without PCP. Phagocytosis by coelomocytes in earthworms exposed to HWS soil, spiked AS and treated FP was suppressed 37, 41 and 29%, respectively. Results are discussed in terms of PCP body burdens and exposure protocols.« less

Toxicity of sediments from a mangrove forest patch in an urban area in Pernambuco (Brazil).

PubMed

Oliveira, D D; Souza-Santos, L P; Silva, H K P; Macedo, S J

2014-06-01

Industrial and urban residues are discharged every day to the rivers and may arrive at the mangrove forest and prejudice the quality of the environment and the organisms present there. The mangrove forest patch studied is encircled by an urban area of the city of Recife (Brazil) that has approximate 1.5 million inhabitants and is one of the most industrialized centers in Northeast Brazil. The aim of this study was to assess the quality of the sediments of this mangrove patch in terms of metal contamination and ecotoxicology. Samples of surface sediment were collected in six stations for toxicological tests and trace metal determination (Cr, Zn, Mn, Fe, Cu, Pb, Co and Ni), in July and August, 2006 (rainy season); and in January and February 2007 (dry season). Toxicity tests with solid-phase sediments were carried out with the copepod Tisbe biminiensis in order to observe lethal and sub-lethal endpoints and correlate them with chemical data. In June, there were no observed lethal effect, but two stations presented sub-lethal effects. In January, lethal effect occurred in three stations and sub-lethal in one station. The levels for Zn and Cr were at higher levels than international proposed guidelines (NOAA). There was a negative significant correlation between the copepods׳ fecundity, and Zn and Cr concentrations. Therefore, the studied sediments can be considered to have potential toxic to benthos due to the high content of Zn and Cr. Copyright © 2014 Elsevier Inc. All rights reserved.

Relationship between Sublethal Injury and Microbial Inactivation by the Combination of High Hydrostatic Pressure and Citral or tert-Butyl Hydroquinone ▿

PubMed Central

Somolinos, Maria; García, Diego; Pagán, Rafael; Mackey, Bernard

2008-01-01

The aim was to investigate (i) the occurrence of sublethal injury in Listeria monocytogenes, Escherichia coli, and Saccharomyces cerevisiae after high hydrostatic pressure (HHP) treatment as a function of the treatment medium pH and composition and (ii) the relationship between the occurrence of sublethal injury and the inactivating effect of a combination of HHP and two antimicrobial compounds, tert-butyl hydroquinone (TBHQ) and citral. The three microorganisms showed a high proportion of sublethally injured cells (up to 99.99% of the surviving population) after HHP. In E. coli and L. monocytogenes, the extent of inactivation and sublethal injury depended on the pH and the composition of the treatment medium, whereas in S. cerevisiae, inactivation and sublethal injury were independent of medium pH or composition under the conditions tested. TBHQ alone was not lethal to E. coli or L. monocytogenes but acted synergistically with HHP and 24-h refrigeration, resulting in a viability decrease of >5 log10 cycles of both organisms. The antimicrobial effect of citral depended on the microorganism and the treatment medium pH. Acting alone for 24 h under refrigeration, 1,000 ppm of citral caused a reduction of 5 log10 cycles of E. coli at pH 7.0 and almost 3 log10 cycles of L. monocytogenes at pH 4.0. The combination of citral and HHP also showed a synergistic effect. Our results have confirmed that the detection of sublethal injury after HHP may contribute to the identification of those treatment conditions under which HHP may act synergistically with other preserving processes. PMID:18952869

Vertical transmission of sublethal granulovirus infection in the Indian meal moth, Plodia interpunctella.

PubMed

Burden, J P; Griffiths, C M; Cory, J S; Smith, P; Sait, S M

2002-03-01

Knowledge of the mechanisms of pathogen persistence in relation to fluctuations in host density is crucial to our understanding of disease dynamics. In the case of insect baculoviruses, which are typically transmitted horizontally via a lifestage that can persist outside the host, a key issue that remains to be elucidated is whether the virus can also be transmitted vertically as a sublethal infection. We show that RNA transcripts for the Plodia interpunctella GV granulin gene are present in a high proportion of P. interpunctella insects that survive virus challenge. Granulin is a late-expressed gene that is only transcribed after viral genome replication, its presence thus strongly indicates that viral genome replication has occurred. Almost all insects surviving the virus challenge tested positive for viral RNA in the larval and pupal stage. However, this proportion declined in the emerging adults. Granulin mRNA was also detected in both the ovaries and testes, which may represent a putative mechanism by which reduced fecundity in sublethally affected hosts might be manifested. RNA transcripts were also detected in 60-80% of second-generation larvae that were derived from mating surviving adults, but there was no difference between the sexes, with both males and females capable of transmitting a sublethal infection to their offspring. The data indicate that low-level persistent infection, with at least limited gene expression, can occur in P. interpunctella following survival of a granulovirus challenge. We believe that this is the first demonstration of a persistent, sublethal infection by a baculovirus to be initiated by a sublethal virus dose. We hypothesize that the 'latent' baculovirus infections frequently referred to in the literature may also be low level persistent, sublethal infections resulting from survival from initial baculovirus exposure.

Colony impact of pesticide-induced sublethal effects on honeybee workers: A simulation study using BEEHAVE.

PubMed

Thorbek, Pernille; Campbell, Peter J; Thompson, Helen M

2017-03-01

Research on neonicotinoids and honeybees have changed focus from direct mortality to sublethal effects. In the present study, a published honeybee model, BEEHAVE, is used to compare induced colony level impact of pesticides including direct mortality, poor brood care, disorientation, and increased handling time in oilseed rape and sunflower crops. Actual effects on individual bees will depend on exposure concentrations, but in the present study large effects were enforced. In oilseed rape, poor brood care had the largest colony impact, because it created a bottleneck for spring build-up of the workforce, and colony impact for all effect types peaked 1 mo after exposure ceased. In sunflower, the later exposure changed the response so colony impact peaked during exposure, and the bottleneck was honey store build-up. In all scenarios, good forage mitigated effects substantially. It is concluded that field studies should continue at least 1 mo after exposure to ensure detection of ecologically relevant sublethal effects. The results indicated that even if a sublethal effect is difficult to detect in the field, subsequent ecologically relevant colony level impacts would be clear if studies are continued for 1 mo after exposure. Guidance for regulatory studies recommends extended observation periods, and published field studies already use extended observation periods, so it is concluded that current methods are adequate for detecting ecologically relevant sublethal effects. Although published laboratory and semifield studies conducted under controlled exposure conditions suggest that sublethal effects may occur, published field studies with neonicotinoid seed treatments, naturally foraging bees, and extended observation periods do not report colony-level effects, suggesting that in these studies no ecologically relevant sublethal effects occurred. Environ Toxicol Chem 2017;36:831-840. © 2016 SETAC. © 2016 SETAC.

Fipronil promotes motor and behavioral changes in honey bees (Apis mellifera) and affects the development of colonies exposed to sublethal doses.

PubMed

Zaluski, Rodrigo; Kadri, Samir Moura; Alonso, Diego Peres; Martins Ribolla, Paulo Eduardo; de Oliveira Orsi, Ricardo

2015-05-01

Bees play a crucial role in pollination and generate honey and other hive products; therefore, their worldwide decline is cause for concern. New broad-spectrum systemic insecticides such as fipronil can harm bees and their use has been discussed as a potential threat to bees' survival. In the present study, the authors evaluate the in vitro toxicity of fipronil and note behavioral and motor activity changes in Africanized adult Apis mellifera that ingest or come into contact with lethal or sublethal doses of fipronil. The effects of sublethal doses on brood viability, population growth, behavior, and the expression of the defensin 1 gene in adult bees were studied in colonies fed with contaminated sugar syrup (8 µg fipronil L(-1) ). Fipronil is highly toxic to bees triggering agitation, seizures, tremors, and paralysis. Bees that are exposed to a lethal or sublethal doses showed reduced motor activity. The number of eggs that hatched, the area occupied by worker eggs, and the number of larvae and pupae that developed were reduced, adult bees showed lethargy, and colonies were abandoned when they were exposed to sublethal doses of fipronil. No change was seen in the bees' expression of defensin 1. The authors conclude that fipronil is highly toxic to honey bees and even sublethal doses may negatively affect the development and maintenance of colonies. © 2015 SETAC.

Kinetics of plasma procalcitonin, soluble CD14, CCL2 and IL-10 after a sublethal infusion of lipopolysaccharide in horses.

PubMed

Bonelli, Francesca; Meucci, Valentina; Divers, Thomas J; Wagner, Bettina; Intorre, Luigi; Sgorbini, Micaela

2017-02-01

Endotoxemia represents a significant clinical and economic problem for the equine industry. This study assesses the kinetics of soluble CD14 (sCD14), chemokine (CC motif) ligand 2 (CCL2), interleukin 10 (IL-10) and plasma procalcitonin (PCT) in healthy horses after the intravenous infusion of lipopolysaccharide (LPS). The aim was to contribute to the basic understanding of the equine species-specific kinetics of these molecules in response to LPS exposure, which could support further findings in clinical studies and identify valuable inflammatory biomarkers for equine practice. Eleven healthy horses were involved in this experimental in vivo study. Horses were classified as healthy before the LPS infusion. After the pre-infusion blood collection (T0), all horses received an infusion of E. coli endotoxin (30ng/kg over 30min). Data and samples were collected 1h (T1), 2 (T2), 3 (T3) and 24h (T24) after infusion. Plasma sCD14, CCL2 and IL-10 were evaluated with a fluorescent bead-based assay, while PCT was evaluated with an equine PCT ELISA assay. A one-way ANOVA test was performed between each blood-sampling time for PCT, sCD14 and IL-10, and a Friedman test was performed for CCL2. Plasma PCT, IL-10 and CCL2 concentrations increased statistically significantly at T1, T2 and T3 compared to T0. No statistically significant differences were found between plasma IL-10 and CCL2 concentrations between T0 vs T24, although plasma PCT values remained high 24h after LPS infusion. Plasma sCD14 concentration showed no statistically significant differences for any of sampling times. Our results demonstrate that LPS injection into healthy horses results in PCT, CCL2 and IL-10 increases in plasma without an increase in sCD14. The increases in PCT, CCL2 and IL-10 are related to the inflammatory response induced by circulating lipopolysaccharide. Copyright © 2016 Elsevier B.V. All rights reserved.

High-level dietary cadmium exposure is associated with global DNA hypermethylation in the gastropod hepatopancreas

PubMed Central

Popescu, Cristina; Draghici, George A.; Andrica, Florina-Maria; Privistirescu, Ionela A.; Gergen, Iosif I.; Stöger, Reinhard

2017-01-01

5-methylcytosine (5mC) is a key epigenetic mark which influences gene expression and phenotype. In vertebrates, this epigenetic mark is sensitive to Cd exposure, but there is no information linking such an event with changes in global 5mC levels in terrestrial gastropods despite their importance as excellentecotoxicological bioindicators of metal contamination. Therefore, we first evaluated total 5mC content in DNA of the hepatopancreas of adult Cantareus aspersus with the aim to determine whether this epigenetic mark is responsive to Cd exposure. The experiment was conducted under laboratory conditions and involved a continuous exposure, multiple dose- and time-point (14, 28, and 56 days) study design. Hepatopancreas cadmium levels were measured using Flame Atomic Absorption Spectrometry and the percentage of 5-mC in samples using an ELISA-based colorimetric assay. Snail death rates were also assessed. Our results, for the first time, reveal the presence of 5mC in C. aspersus and provide evidence for Cd-induced changes in global 5mC levels in DNA of gastropods and mollusks. Although less sensitive than tissue accumulation, DNA methylation levels responded in a dose- and time-dependent manner to dietary cadmium, with exposure dose having a much stronger effect than exposure duration. An obvious trend of increasing 5mC levels was observed starting at 28 days of exposure to the second highest dose and this trend persisted at the two highest treatments for close to one month, when the experiment was terminated after 56 days. Moreover, a strong association was identified between Cd concentrations in the hepatopancreas and DNA methylation levels in this organ. These data indicate an overall trend towards DNA hypermethylation with elevated Cd exposure. No consistent lethal effect was observed, irrespective of time point and Cd-dosage. Overall, our findings suggest that the total 5mC content in DNA of the hepatopancreas of land snails is responsive to sublethal Cd exposure and give new insights into invertebrate environmental epigenetics. PMID:28877233

Effect of disinfectants on stability and transmissibility of R-plasmid in E. coli isolated from drinking water.

PubMed

Tewari, Suman; Ramteke, Pramod W; Garg, S K

2003-03-01

Drug resistant enteropathogenic E. coli (EPEC, 086 serotype) isolated from contaminated piped drinking water supply (Fecal coliform 160/100 ml) was studied for effect of disinfectants (chlorine and UVB) on stability and transmissibility of R-plasmid. The strain was resistant to streptomycin and bacitracin and tolerant to multiple metal ions of Cd, Cr, Co, As, Ni, Zn and Hg. A plasmid of molecular size of 3.7 Kb was detected in the organism. After exposure to sublethal doses of disinfectants, complete elimination of resistances to streptomycin and Cr was observed. Partial loss of resistance to Hg due to chlorine was detected. Although UVB did not effected the pattern of transmissibility effect on frequency of transfer was observed. Surprisingly, in UVB irradiated cells, significantly enhanced rate of transfer was noted.

The Glyphosate-Based Herbicide Roundup Does not Elevate Genome-Wide Mutagenesis of Escherichia coli.

PubMed

Tincher, Clayton; Long, Hongan; Behringer, Megan; Walker, Noah; Lynch, Michael

2017-10-05

Mutations induced by pollutants may promote pathogen evolution, for example by accelerating mutations conferring antibiotic resistance. Generally, evaluating the genome-wide mutagenic effects of long-term sublethal pollutant exposure at single-nucleotide resolution is extremely difficult. To overcome this technical barrier, we use the mutation accumulation/whole-genome sequencing (MA/WGS) method as a mutagenicity test, to quantitatively evaluate genome-wide mutagenesis of Escherichia coli after long-term exposure to a wide gradient of the glyphosate-based herbicide (GBH) Roundup Concentrate Plus. The genome-wide mutation rate decreases as GBH concentration increases, suggesting that even long-term GBH exposure does not compromise the genome stability of bacteria. Copyright © 2017 Tincher et al.

Effects of Multiple Routes of Cadmium Exposure on the Hibernation Success of the American Toad (Bufo americanus)

USGS Publications Warehouse

James, S.M.; Little, E.E.; Semlitsch, R.D.

2004-01-01

The effects of multiple routes of cadmium exposure on juvenile American toads (Bufo americanus) were evaluated using environmentally relevant concentrations. During or after exposure, toads were individually hibernated for 172 days at approximately 4??C. The following experiments were conducted: (1) dermal exposure (hibernation in soil contaminated with up to 120 ??g Cd/ g (dry weight)); (2) injection exposure (single injection with cadmium to achieve a maximum whole-body nominal concentration of 3 ??g Cd/g (wet weight) 12 days before hibernation in uncontaminated soil); and, (3) oral exposure (feeding with mealworms containing ???16 ??g Cd/g (dry weight) for 50 days before hibernation in uncontaminated soil)., We hypothesized that sublethal levels of cadmium would become lethal during hibernation because of combined chemical and cold stress. No prehibernation mortality occurred in the injection and oral exposure studies. There was a significant treatment effect on whole-body cadmium concentration in toads orally or dermally exposed and on percent of cadmium retention in toads orally exposed. There was also a trend of increased time-to-burrowing and more toads partially buried with greater cadmium concentration in the dermal study, which indicated avoidance. In all 3 experiments, no significant differences were found among cadmium treatments in hibernation survival, percent of mass loss, or locomotor performance. However, toads fed mealworms averaging 4.7 ??g Cd/g (dry weight) had only 56% survival compared with 100% survival for controls. Although our results suggest that environmentally relevant levels of cadmium do not pose a great risk to American toads, factors such as soil type or prey species may increase cadmium bioavailability, and other amphibian species may be more sensitive to cadmium than B. americanus.

Toxicity of organic and inorganic nanoparticles to four species of white-rot fungi.

PubMed

Galindo, T P S; Pereira, R; Freitas, A C; Santos-Rocha, T A P; Rasteiro, M G; Antunes, F; Rodrigues, D; Soares, A M V M; Gonçalves, F; Duarte, A C; Lopes, I

2013-08-01

The rapid development of nanoparticles (NP) for industrial applications and large-volume manufacturing, with its subsequent release into the environment, raised the need to understand and characterize the potential effects of NP to biota. Accordingly, this work aimed to assess sublethal effects of five NP to the white-rot fungi species Trametes versicolor, Lentinus sajor caju, Pleurotus ostreatus, and Phanerochaete chrysosporium. Each species was exposed to serial dilutions of the following NP: organic-vesicles of SDS/DDAB and of Mo/NaO; gold-NP, quantum dot CdSe/ZnS, and Fe/Co. Fungi growth rate was monitored every day, and at the end of assay the mycelium from each replicate was collected to evaluate possible changes in its chemical composition. For all NP-suspensions the following parameters were characterized: hydrodynamic diameter, surface charge, aggregation index, zeta potential, and conductivity. All tested NP tended to aggregate when suspended in aqueous media. The obtained results showed that gold-NP, CdSe/ZnS, Mo/NaO, and SDS/DDAB significantly inhibited the growth of fungi with effects on the mycelium chemical composition. Among the tested NP, gold-NP and CdSe/ZnS were the ones exerting a higher effect on the four fungi. Finally to our knowledge, this is the first study reporting that different types of NP induce changes in the chemical composition of fungi mycelium. Copyright © 2013 Elsevier B.V. All rights reserved.

Oxidative stress in freshwater fish, Labeo rohita as a biomarker of malathion exposure.

PubMed

Patil, Vineetkumar K; David, Muniswamy

2013-12-01

This study examined the effect of lethal (4.5 μg/l) and sublethal (0.45 μg/l) malathion levels on oxidative stress responses of the freshwater edible fish, Labeo rohita. Fish were exposed to lethal (1-4 days) and sublethal (1, 5, 10, and 15 days) periods. In the present study, catalase and protease activity, hydrogen peroxide, malondialdehyde, protein carbonyls, and free amino acids levels increased in the gill, liver, and kidney tissues of fish exposed to lethal and sublethal concentrations of malathion except protein content. Time- and concentration-dependent induction/reduction of the above parameters by lethal and sublethal concentrations of malathion was observed in the tissues (the gill, liver, and kidney) of L. rohita. Thus, the results clearly infer oxidative damage and decline in antioxidant defense due to malathion-induced oxidative stress.

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

PubMed

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.

Acute and persistent toxicity of Cd(II) to the microbial community of Anammox process.

PubMed

Zhang, Xiaojing; Chen, Zhao; Ma, Yongpeng; Zhao, Jianguo; Chen, Tao; Fu, Haoqiang; Zhai, Hanfei

2018-08-01

In this study, the short- and long-term effects of Cd(II) on the bioactivity, nitrogen removal and microbial community of the anaerobic ammonia oxidation (Anammox) process were investigated by step-wise increasing Cd(II). The self-recovery ability of Anammox was also studied after long-term exposure in Cd(II). The bioactivity of anaerobic ammonia-oxidizing bacteria (AAOB) within short-term exposure of Cd(II) were detected by batch experiments. Results showed that Cd(II) had both acute and persistent toxicity to Anammox, the IC 50 in short-term exposure was calculated as 5.43 mg L -1 . Long-term exposure led to the microbial diversity increase, as well as the relative abundance decrease of AAOB in Anammox system. AAOB was continuously suppressed by Cd(II) in 1-20 mg L -1 , while it had self-adaption to Cd(II) in 1-10 mg L -1 . Anammox biofilm showed prominent adsorbing ability for cadmium, and the cadmium in biofilm was the key factor affecting Anammox. Copyright © 2018 Elsevier Ltd. All rights reserved.

Trace element concentrations in feathers and blood of Northern goshawk (Accipiter gentilis) nestlings from Norway and Spain.

PubMed

Dolan, Kevin J; Ciesielski, Tomasz M; Lierhagen, Syverin; Eulaers, Igor; Nygård, Torgeir; Johnsen, Trond V; Gómez-Ramírez, Pilar; García-Fernández, Antonio J; Bustnes, Jan O; Ortiz-Santaliestra, Manuel E; Jaspers, Veerle L B

2017-10-01

Information on trace element pollution in the terrestrial environment and its biota is limited compared to the marine environment. In the present study, we collected body feathers and blood of 37 Northern goshawk (Accipiter gentilis) nestlings from Tromsø (northern Norway), Trondheim (central Norway), and Murcia (southeastern Spain) to study regional exposure, hypothesizing the potential health risks of metals and other trace elements. Blood and body feathers were analyzed by a high resolution inductively coupled plasma mass spectrometer (HR-ICP-MS) for aluminum (Al), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), cadmium (Cd), mercury (Hg) and lead (Pb). The influence of regional differences, urbanization and agricultural land usage in proximity to the nesting Northern goshawks was investigated using particular spatial analysis techniques. Most trace elements were detected below literature blood toxicity thresholds, except for elevated concentrations (mean ± SD µgml -1 ww) found for Zn (5.4 ± 1.5), Cd (0.00023 ± 0.0002), and Hg (0.021 ± 0.01). Corresponding mean concentrations in feathers (mean ± SD µgg -1 dw) were 82.0 ± 12.4, 0.0018 ± 0.002, and 0.26 ± 0.2 for Zn, Cd and Hg respectively. Multiple linear regressions indicated region was a significant factor influencing Al, Zn, Se and Hg feather concentrations. Blood Cd and Hg concentrations were significantly influenced by agricultural land cover. Urbanization did not have a significant impact on trace element concentrations in either blood or feathers. Overall metal and trace element levels do not indicate a high risk for toxic effects in the nestlings. Levels of Cd in Tromsø and Hg in Trondheim were however above sub-lethal toxic threshold levels. For holistic risk assessment purposes it is important that the concentrations found in the nestlings of this study indicate that terrestrial raptors are exposed to various trace elements. Copyright © 2017 Elsevier Inc. All rights reserved.

Recombination-activating gene 1 (Rag1)-deficient mice with severe combined immunodeficiency treated with lentiviral gene therapy demonstrate autoimmune Omenn-like syndrome.

PubMed

van Til, Niek P; Sarwari, Roya; Visser, Trudi P; Hauer, Julia; Lagresle-Peyrou, Chantal; van der Velden, Guus; Malshetty, Vidyasagar; Cortes, Patricia; Jollet, Arnaud; Danos, Olivier; Cassani, Barbara; Zhang, Fang; Thrasher, Adrian J; Fontana, Elena; Poliani, Pietro L; Cavazzana, Marina; Verstegen, Monique M A; Villa, Anna; Wagemaker, Gerard

2014-04-01

Recombination-activating gene 1 (RAG1) deficiency results in severe combined immunodeficiency (SCID) caused by a complete lack of T and B lymphocytes. If untreated, patients succumb to recurrent infections. We sought to develop lentiviral gene therapy for RAG1-induced SCID and to test its safety. Constructs containing the viral spleen-focus-forming virus (SF), ubiquitous promoters, or cell type-restricted promoters driving sequence-optimized RAG1 were compared for efficacy and safety in sublethally preconditioned Rag1(-/-) mice undergoing transplantation with transduced bone marrow progenitors. Peripheral blood CD3(+) T-cell reconstitution was achieved with SF, ubiquitous promoters, and cell type-restricted promoters but 3- to 18-fold lower than that seen in wild-type mice, and with a compromised CD4(+)/CD8(+) ratio. Mitogen-mediated T-cell responses and T cell-dependent and T cell-independent B-cell responses were not restored, and T-cell receptor patterns were skewed. Reconstitution of mature peripheral blood B cells was approximately 20-fold less for the SF vector than in wild-type mice and often not detectable with the other promoters, and plasma immunoglobulin levels were abnormal. Two months after transplantation, gene therapy-treated mice had rashes with cellular tissue infiltrates, activated peripheral blood CD44(+)CD69(+) T cells, high plasma IgE levels, antibodies against double-stranded DNA, and increased B cell-activating factor levels. Only rather high SF vector copy numbers could boost T- and B-cell reconstitution, but mRNA expression levels during T- and B-cell progenitor stages consistently remained less than wild-type levels. These results underline that further development is required for improved expression to successfully treat patients with RAG1-induced SCID while maintaining low vector copy numbers and minimizing potential risks, including autoimmune reactions resembling Omenn syndrome. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Pre-treatment with Lactobacillus plantarum prevents severe pathogenesis in mice infected with Leptospira interrogans and may be associated with recruitment of myeloid cells

PubMed Central

Potula, Hari-Hara; Richer, Luciana; Werts, Catherine

2017-01-01

Recent estimates on global morbidity and mortality caused by Leptospirosis point to one million cases and almost 60,000 deaths a year worldwide, especially in resource poor countries. We analyzed how a commensal probiotic immunomodulator, Lactobacillus plantarum, affects Leptospira interrogans pathogenesis in a murine model of sub-lethal leptospirosis. We found that repeated oral pre-treatment of mice with live L. plantarum restored body weight to normal levels in mice infected with L. interrogans. Pre-treatment did not prevent L. interrogans access to the kidney but it affected the inflammatory response and it reduced histopathological signs of disease. Analysis of the immune cell profiles in lymphoid tissues of mice pre-treated with L. plantarum showed increased numbers of B cells as well as naïve and memory CD4+ helper T cell populations in uninfected mice that shifted towards increased numbers of effector CD4+ helper T in infected mice. CD8+ cytotoxic T cell profiles in pre-treated uninfected and infected mice mirrored the switch observed for CD4+ except that CD8+ memory T cells were not affected. In addition, pre-treatment led to increased populations of monocytes in lymphoid tissues of uninfected mice and to increased populations of macrophages in the same tissues of infected mice. Immunohistochemistry of kidney sections of pre-treated infected mice showed an enrichment of neutrophils and macrophages and a reduction of total leucocytes and T cells. Our results suggest that complex myeloid and T cell responses orchestrate the deployment of monocytes and other cells from lymphoid tissue and the recruitment of neutrophils and macrophages to the kidney, and that, the presence of these cells in the target organ may be associated with reductions in pathogenesis observed in infected mice treated with L. plantarum. PMID:28841659

Mechanical Blood Trauma in Assisted Circulation: Sublethal RBC Damage Preceding Hemolysis

PubMed Central

Olia, Salim E.; Maul, Timothy M.; Antaki, James F.; Kameneva, Marina V.

2016-01-01

After many decades of improvements in mechanical circulatory assist devices (CADs), blood damage remains a serious problem during support contributing to variety of adverse events, and consequently affecting patient survival and quality of life. The mechanisms of cumulative cell damage in continuous-flow blood pumps are still not fully understood despite numerous in vitro, in vivo, and in silico studies of blood trauma. Previous investigations have almost exclusively focused on lethal blood damage, namely hemolysis, which is typically negligible during normal operation of current generation CADs. The measurement of plasma free hemoglobin (plfHb) concentration to characterize hemolysis is straightforward, however sublethal trauma is more difficult to detect and quantify since no simple direct test exists. Similarly, while multiple studies have focused on thrombosis within blood pumps and accessories, sublethal blood trauma and its sequelae have yet to be adequately documented or characterized. This review summarizes the current understanding of sublethal trauma to red blood cells (RBCs) produced by exposure of blood to flow parameters and conditions similar to those within CADs. It also suggests potential strategies to reduce and/or prevent RBC sublethal damage in a clinically-relevant context, and encourages new research into this relatively uncharted territory. PMID:27034320

EVALUATION OF SUBLETHAL EFFECTS OF Ipomoea cairica LINN. EXTRACT ON LIFE HISTORY TRAITS OF DENGUE VECTORS

PubMed Central

ZUHARAH, Wan Fatma; AHBIRAMI, Rattanam; DIENG, Hamady; THIAGALETCHUMI, Maniam; FADZLY, Nik

2016-01-01

Plant derived insecticides have considerable potential for mosquito control because these products are safer than conventional insecticides. This study aimed to investigate sublethal activities of Ipomoea carica or railway creeper crude acethonilic extract against life history trait of dengue vectors, Aedes albopictus and Aedes aegypti. The late third instar larvae of Ae. albopictus and Ae. aegypti were exposed to a sublethal dose at LC50 and larvae that survived were further cultured. Overall, Ipomea cairica crude extracts affected the whole life history of both Aedes species. The study demonstrated significantly lower egg production (fecundity) and eggs hatchability (fertility) in Ae. albopictus. The sublethal dose of crude extracts reduced significantly the width of larval head capsule and the wing length of both sexes in both Aedes species. The significance of sublethal effects of I. cairica against Aedes mosquitoes was an additional hallmark to demonstrate further activity of this plant despite its direct toxicity to the larvae. The reduced reproductive capacity as well as morphological and physiological anomalies are some of the effects that make I. cairica a potential candidate to be used as a new plant-based insecticide to control dengue vectors. PMID:27253746

Green-synthesized CdS nano-pesticides: Toxicity on young instars of malaria vectors and impact on enzymatic activities of the non-target mud crab Scylla serrata.

PubMed

Sujitha, Vasu; Murugan, Kadarkarai; Dinesh, Devakumar; Pandiyan, Amuthvalli; Aruliah, Rajasekar; Hwang, Jiang-Shiou; Kalimuthu, Kandasamy; Panneerselvam, Chellasamy; Higuchi, Akon; Aziz, Al Thabiani; Kumar, Suresh; Alarfaj, Abdullah A; Vaseeharan, Baskaralingam; Canale, Angelo; Benelli, Giovanni

2017-07-01

Currently, nano-formulated mosquito larvicides have been widely proposed to control young instars of malaria vector populations. However, the fate of nanoparticles in the aquatic environment is scarcely known, with special reference to the impact of nanoparticles on enzymatic activity of non-target aquatic invertebrates. In this study, we synthesized CdS nanoparticles using a green protocol relying on the cheap extract of Valoniopsis pachynema algae. CdS nanoparticles showed high toxicity on young instars of the malaria vectors Anopheles stephensi and A. sundaicus. The antimalarial activity of the nano-synthesized product against chloroquine-resistant (CQ-r) Plasmodium falciparum parasites was investigated. From a non-target perspective, we focused on the impact of this novel nano-pesticide on antioxidant enzymes acetylcholinesterase (AChE) and glutathione S-transferase (GST) activities of the mud crab Scylla serrata. The characterization of nanomaterials was carried out by UV-vis and FTIR spectroscopy, as well as SEM and XRD analyses. In mosquitocidal assays, LC 50 of V. pachynema-synthesized CdS nanoparticles on A. stephensi ranged from 16.856 (larva I), to 30.301μg/ml (pupa), while for An. sundaicus they ranged from 13.584 to 22.496μg/ml. The antiplasmodial activity of V. pachynema extract and CdS nanoparticles was evaluated against CQ-r and CQ-sensitive (CQ-s) strains of Plasmodium falciparum. IC 50 of V. pachynema extract was 58.1μg/ml (CQ-s) and 71.46μg/ml (CQ-r), while nano-CdS IC 50 was 76.14μg/ml (CQ-s) and 89.21μg/ml (CQ-r). In enzymatic assays, S. serrata crabs were exposed to sub-lethal concentrations, i.e. 4, 6 and 8μg/ml of CdS nanoparticles, assessing changes in GST and AChE activity after 16days. We observed significantly higher activity of GST, if compared to the control, during the whole experiment period. In addition, a single treatment with CdS nanoparticles led to a significant decrease in AChE activity over time. The toxicity of CdS nanoparticles and Cd ions in aqueous solution was also assessed in mud crabs, showing higher toxicity of aqueous Cd ions if compared to nano-CdS. Overall, our results underlined the efficacy of green-synthesized CdS nanoparticles in malaria vector control, outlining also significant impacts on the enzymatic activity of non-target aquatic organisms, with special reference to mud crabs. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessment of Potential Sublethal Effects of Various Insecticides on Key Biological Traits of The Tobacco Whitefly, Bemisia tabaci

PubMed Central

He, Yuxian; Zhao, Jianwei; Zheng, Yu; Weng, Qiyong; Biondi, Antonio; Desneux, Nicolas; Wu, Kongming

2013-01-01

The tobacco whitefly Bemisia tabaci is one of the most devastating pests worldwide. Current management of B. tabaci relies upon the frequent applications of insecticides. In addition to direct mortality by typical acute toxicity (lethal effect), insecticides may also impair various key biological traits of the exposed insects through physiological and behavioral sublethal effects. Identifying and characterizing such effects could be crucial for understanding the global effects of insecticides on the pest and therefore for optimizing its management in the crops. We assessed the effects of sublethal and low-lethal concentrations of four widely used insecticides on the fecundity, honeydew excretion and feeding behavior of B. tabaci adults. The probing activity of the whiteflies feeding on treated cotton seedlings was recorded by an Electrical Penetration Graph (EPG). The results showed that imidacloprid and bifenthrin caused a reduction in phloem feeding even at sublethal concentrations. In addition, the honeydew excretions and fecundity levels of adults feeding on leaf discs treated with these concentrations were significantly lower than the untreated ones. While, sublethal concentrations of chlorpyrifos and carbosulfan did not affect feeding behavior, honeydew excretion and fecundity of the whitefly. We demonstrated an antifeedant effect of the imidacloprid and bifenthrin on B. tabaci, whereas behavioral changes in adults feeding on leaves treated with chlorpyrifos and carbosulfan were more likely caused by the direct effects of the insecticides on the insects' nervous system itself. Our results show that aside from the lethal effect, the sublethal concentration of imidacloprid and bifenthrin impairs the phloem feeding, i.e. the most important feeding trait in a plant protection perspective. Indeed, this antifeedant property would give these insecticides potential to control insect pests indirectly. Therefore, the behavioral effects of sublethal concentrations of imidacloprid and bifenthrin may play an important role in the control of whitefly pests by increasing the toxicity persistence in treated crops. PMID:23494876

Age and CD4 count at initiation of antiretroviral therapy in HIV-infected children: effects on long-term T-cell reconstitution.

PubMed

Lewis, Joanna; Walker, A Sarah; Castro, Hannah; De Rossi, Anita; Gibb, Diana M; Giaquinto, Carlo; Klein, Nigel; Callard, Robin

2012-02-15

Effective therapies and reduced AIDS-related morbidity and mortality have shifted the focus in pediatric human immunodeficiency virus (HIV) from minimizing short-term disease progression to maintaining optimal long-term health. We describe the effects of children's age and pre-antiretroviral therapy (ART) CD4 count on long-term CD4 T-cell reconstitution. CD4 counts in perinatally HIV-infected, therapy-naive children in the Paediatric European Network for the Treatment of AIDS 5 trial were monitored following initiation of ART for a median 5.7 years. In a substudy, naive and memory CD4 counts were recorded. Age-standardized measurements were analyzed using monophasic, asymptotic nonlinear mixed-effects models. One hundred twenty-seven children were studied. Older children had lower age-adjusted CD4 counts in the long term and at treatment initiation (P < .001). At all ages, lower counts before treatment were associated with impaired recovery (P < .001). Age-adjusted naive CD4 counts increased on a timescale comparable to overall CD4 T-cell reconstitution, whereas age-adjusted memory CD4 counts increased less, albeit on a faster timescale. It appears the immature immune system can recover well from HIV infection via the naive pool. However, this potential is progressively damaged with age and/or duration of infection. Current guidelines may therefore not optimize long-term immunological health.

Sublethal Dosage of Imidacloprid Reduces the Microglomerular Density of Honey Bee Mushroom Bodies

PubMed Central

Peng, Yi-Chan; Yang, En-Cheng

2016-01-01

The dramatic loss of honey bees is a major concern worldwide. Previous studies have indicated that neonicotinoid insecticides cause behavioural abnormalities and have proven that exposure to sublethal doses of imidacloprid during the larval stage decreases the olfactory learning ability of adults. The present study shows the effect of sublethal doses of imidacloprid on the neural development of the honey bee brain by immunolabelling synaptic units in the calyces of mushroom bodies. We found that the density of the synaptic units in the region of the calyces, which are responsible for olfactory and visual functions, decreased after being exposed to a sublethal dose of imidacloprid. This not only links a decrease in olfactory learning ability to abnormal neural connectivity but also provides evidence that imidacloprid damages the development of the nervous system in regions responsible for both olfaction and vision during the larval stage of the honey bee. PMID:26757950

Short and long-term effects of three neurotoxic insecticides on biological and behavioural attributes of the orb-web spider Alpaida veniliae (Araneae, Araneidae): implications for IPM programs.

PubMed

Benamú, Marco A; Schneider, Marcela I; González, Alda; Sánchez, Norma E

2013-09-01

Soybean pest control in Argentina is done just by chemical control using broad-spectrum pesticides. Alpaida veniliae (Araneae, Araneidae) is one of the most abundant spider species of the orb web weaver guild in soybean, and it is considered a very important polyphagous predator, attacking different insects' families. The objective of this study was to determine if neurotoxic insecticides commonly used in soybean crops and a new active ingredient registered in Argentina (spinosad) adversely affected survival, prey consumption, mating behaviour, web building and reproductive capacity of A. veniliae females, under standard laboratory conditions. Spinosad was the most harmful insecticide due to high acute toxicity, even at lower concentrations than those registered for its field use and for its sublethal effects also. Cypermethrin caused several sublethal effects although its acute toxicity on spider was lower than other insecticides. It reduced prey consumption, affected web building, caused abnormalities in eggs sacs and decreased drastically the fecundity and fertility at sublethal concentrations. Endosulfan did not reduce prey consumption but it affected web building, caused abnormalities in eggs sacs and egg masses, and decreased the fecundity and fertility. Spinosad was also the compound with the most drastic effect on web building, it did not reduce prey consumption and fecundity, but fertility was reduced and abnormalities in egg sacs and egg masses were observed. The use of these insecticides in IPM programs according to their potential toxicity on spider communities is discussed.

Larval Mid-Gut Responses to Sub-Lethal Dose of Cry Toxin in Lepidopteran Pest Achaea janata.

PubMed

Chauhan, Vinod K; Dhania, Narender K; Chaitanya, R K; Senthilkumaran, Balasubramanian; Dutta-Gupta, Aparna

2017-01-01

The lack of homogeneity in field application of Bacillus thuringiensis formulation often results in ingestion of sub-lethal doses of the biopesticide by a fraction of pest population and there by promotes the toxin tolerance and resistance in long term. Gut regeneration seems to be one of the possible mechanism by which this is accomplished. However, the existing information is primarily derived from in vitro studies using mid-gut cell cultures. Present study illustrates cellular and molecular changes in mid-gut epithelium of a Bt -susceptible polyphagous insect pest castor semilooper, Achaea janata in response to a Cry toxin formulation. The present report showed that prolonged exposure to sub-lethal doses of Cry toxin formulation has deleterious effect on larval growth and development. Histological analysis of mid-gut tissue exhibits epithelial cell degeneration, which is due to necrotic form of cell death followed by regeneration through enhanced proliferation of mid-gut stem cells. Cell death is demonstrated by confocal microscopy, flow-cytometry, and DNA fragmentation analysis. Cell proliferation in control vs. toxin-exposed larvae is evaluated by bromodeoxyuridine (BrdU) labeling and toluidine blue staining. Intriguingly, in situ mRNA analysis detected the presence of arylphorin transcripts in larval mid-gut epithelial cells. Quantitative PCR analysis further demonstrates altered expression of arylphorin gene in toxin-exposed larvae when compared with the control. The coincidence of enhanced mid-gut cell proliferation coincides with the elevated arylphorin expression upon Cry intoxication suggests that it might play a role in the regeneration of mid-gut epithelial cells.

Effects of sublethal doses of glyphosate on honeybee navigation.

PubMed

Balbuena, María Sol; Tison, Léa; Hahn, Marie-Luise; Greggers, Uwe; Menzel, Randolf; Farina, Walter M

2015-09-01

Glyphosate (GLY) is a herbicide that is widely used in agriculture for weed control. Although reports about the impact of GLY in snails, crustaceans and amphibians exist, few studies have investigated its sublethal effects in non-target organisms such as the honeybee Apis mellifera, the main pollen vector in commercial crops. Here, we tested whether exposure to three sublethal concentrations of GLY (2.5, 5 and 10 mg l(-1): corresponding to 0.125, 0.250 and 0.500 μg per animal) affects the homeward flight path of honeybees in an open field. We performed an experiment in which forager honeybees were trained to an artificial feeder, and then captured, fed with sugar solution containing traces of GLY and released from a novel site either once or twice. Their homeward trajectories were tracked using harmonic radar technology. We found that honeybees that had been fed with solution containing 10 mg l(-1) GLY spent more time performing homeward flights than control bees or bees treated with lower concentrations. They also performed more indirect homing flights. Moreover, the proportion of direct homeward flights performed after a second release from the same site increased in control bees but not in treated bees. These results suggest that, in honeybees, exposure to levels of GLY commonly found in agricultural settings impairs the cognitive capacities needed to retrieve and integrate spatial information for a successful return to the hive. Therefore, honeybee navigation is affected by ingesting traces of the most widely used herbicide worldwide, with potential long-term negative consequences for colony foraging success. © 2015. Published by The Company of Biologists Ltd.

Effects of sub-lethal doses of glyphosate on honeybee navigation.

PubMed

Sol Balbuena, María; Tison, Léa; Hahn, Marie-Luise; Greggers, Uwe; Menzel, Randolf; Farina, Walter M

2015-07-10

Glyphosate (GLY) is a herbicide that is widely used in agriculture for weed control. Although reports about the impact of GLY in snails, crustaceans and amphibians exist, few studies have investigated its sub-lethal effects in non-target organisms such as the honeybee Apis mellifera, the main pollen vector in commercial crops. Here, we tested whether exposure to three sub-lethal concentrations of GLY (2.5, 5 and 10 mg/L corresponding to 0.125, 0.250 and 0.500 µg/animal) affects the homeward flight path of honeybees in an open field. We performed an experiment in which forager honeybees were trained to an artificial feeder, and then captured, fed with sugar solution containing GLY traces and released from a novel site (the release site, RS) either once or twice. Their homeward trajectories were tracked using harmonic radar technology. We found that honeybees that had been fed with solution containing 10 mg/L GLY spent more time performing homeward flights than control bees or bees treated with lower GLY concentrations. They also performed more indirect homing flights. Moreover, the proportion of direct homeward flights performed after a second release at the RS increased in control bees but not in treated bees. These results suggest that, in honeybees, exposure to GLY doses commonly found in agricultural settings impairs the cognitive capacities needed to retrieve and integrate spatial information for a successful return to the hive. Therefore, honeybee navigation is affected by ingesting traces of the most widely used herbicide worldwide, with potential long-term negative consequences for colony foraging success. © 2015. Published by The Company of Biologists Ltd.

Interleukin-12 Induces a Th1-like Response to Burkholderia mallei and Limited Protection in BALB/c Mice

DTIC Science & Technology

2005-09-02

protection from a lethal challenge. 15. SUBJECT TERMS Burkholderia mallei , glanders , cytokines, immune response, humoral, cellular, laboratory animals...model of sublethal and lethal intraperitoneal glanders ( Burkholderia mallei ). Vet Pathol 2000;37:626–36. [34] Jankovic D, Caspar P, Zweig M, Garcia...Vaccine 24 (2006) 1413–1420 Interleukin-12 induces a Th1-like response to Burkholderia mallei and limited protection in BALB/c mice Kei Amemiya

Molecular responses in digestive tract of juvenile common carp after chronic exposure to sublethal tributyltin.

PubMed

Li, Zhi-Hua; Li, Ping; Shi, Ze-Chao

2014-11-01

The effect of long-term exposure to tributyltin (TBT) on the intestine-related biochemical biomarkers in common carp was investigated in this study. Fish were exposed at sub-lethal concentrations of TBT (75 ng/L, 0.75 and 7.5 μg/L) for 60 days. Multiple biomarkers were measured, including digestive enzymes (trypsin, lipase and amylase), antioxidant responses (malondialdehyde (MDA) and total antioxidative capacity (T-AOC)), RNA/DNA ratio and the expression of digestive-related genes (try, lipc and amy). TBT exposure at 0.75 and 7.5 μg/L led to significantly inhibited activities of all digestive enzymes. At higher concentration of TBT, oxidative stress was apparent as reflected by the significant higher MDA content in the fish intestine, associated with an inhibition of T-AOC activities. After 60 days, the RNA/DNA ratio in fish intestine was significantly lower in groups exposed to TBT at higher concentrations (0.75 and 7.5 μg/L). In addition, the expression levels of try, lipc and amy in intestine of all treated fish were inhibited, even at the environmental concentration (75 ng/L). Our results suggest that long-term exposure to TBT could result in different responses of intestine-related biochemical biomarkers in fish, which could be used as new potential indicators for monitoring residual TBT present in aquatic environment. Copyright © 2014 Elsevier Inc. All rights reserved.

Ageing and long-term CD4 cell count trends in HIV-positive patients with 5 years or more combination antiretroviral therapy experience.

PubMed

Wright, S T; Petoumenos, K; Boyd, M; Carr, A; Downing, S; O'Connor, C C; Grotowski, M; Law, M G

2013-04-01

The aim of this study was to describe the long-term changes in CD4 cell counts beyond 5 years of combination antiretroviral therapy (cART). If natural ageing leads to a long-term decline in the immune system via low-grade chronic immune activation/inflammation, then one might expect to see a greater or earlier decline in CD4 counts in older HIV-positive patients with increasing duration of cART. Retrospective and prospective data were examined from long-term virologically stable HIV-positive adults from the Australian HIV Observational Database. We estimated mean CD4 cell count changes following the completion of 5 years of cART using linear mixed models. A total of 37 916 CD4 measurements were observed for 892 patients over a combined total of 9753 patient-years. Older patients (> 50 years old) at cART initiation had estimated mean (95% confidence interval) changes in CD4 counts by year-5 CD4 count strata (< 500, 500-750 and > 750 cells/μL) of 14 (7 to 21), 3 (-5 to 11) and -6 (-17 to 4) cells/μL/year. Of the CD4 cell count rates of change estimated, none were indicative of long-term declines in CD4 cell counts. Our results suggest that duration of cART and increasing age do not result in decreasing mean changes in CD4 cell counts for long-term virologically suppressed patients, indicating that the level of immune recovery achieved during the first 5 years of treatment is sustained through long-term cART. © 2012 British HIV Association.

Ageing & long-term CD4 cell count trends in HIV-positive patients with 5 years or more combination antiretroviral therapy experience

PubMed Central

WRIGHT, ST; PETOUMENOS, K; BOYD, M; CARR, A; DOWNING, S; O’CONNOR, CC; GROTOWSKI, M; LAW, MG

2012-01-01

Background The aim of this analysis is to describe the long-term changes in CD4 cell counts beyond 5 years of combination antiretroviral therapy (cART). If natural ageing leads to a long-term decline in the immune system via low-grade chronic immune activation/inflammation, then one might expect to see a greater or earlier decline in CD4 counts in older HIV-positive patients with increasing duration of cART. Methods Retrospective and prospective data were examined from long-term virologically stable HIV-positive adults from the Australian HIV Observational Database. We estimated mean CD4 cell counts changes following the completion of 5 years of cART using linear mixed models. Results A total of 37,916 CD4 measurements were observed for 892 patients over a combined total of 9,753 patient years. Older patients (>50 years) at cART initiation had estimated mean(95% confidence interval) change in CD4 counts by Year-5 CD4 count strata (<500, 501–750 and >750 cells/μL) of 14(7 to 21), 3(−5 to 11) and −6(−17 to 4) cells/μL/year. Of the CD4 cell count rates of change estimated, none were indicative of long-term declines in CD4 cell counts. Conclusions Our results suggest that duration of cART and increasing age does not result in decreasing mean changes in CD4 cell counts for long-term virologically suppressed patients. Indicating that level of immune recovery achieved during the first 5 years of treatment are sustained through long-term cART. PMID:23036045

Resistance to Biocides in Listeria monocytogenes Collected in Meat-Processing Environments

PubMed Central

Conficoni, Daniele; Losasso, Carmen; Cortini, Enzo; Di Cesare, Andrea; Cibin, Veronica; Giaccone, Valerio; Corno, Gianluca; Ricci, Antonia

2016-01-01

The emergence of microorganisms exerting resistance to biocides is a challenge to meat-processing environments. Bacteria can be intrinsically resistant to biocides but resistance can also be acquired by adaptation to their sub-lethal concentrations. Moreover, the presence of biocide resistance determinants, which is closely linked to antibiotic resistance determinants, could lead to co-selection during disinfection practices along the food chain, and select cross-resistant foodborne pathogens. The purpose of this work was to test the resistance of wild strains of Listeria monocytogenes, isolated from pork meat processing plants, toward benzalkonium chloride (BC), used as proxy of quaternary ammonium compounds. Furthermore, the expression of two non-specific efflux pumps genes (lde and mdrL) under biocide exposure was evaluated. L. monocytogenes were isolated from five processing plants located in the Veneto region (northeast of Italy) before and after cleaning and disinfection (C&D) procedures. A total of 45 strains were collected: 36 strains before and nine after the C&D procedures. Collected strains were typed according to MLST and ERIC profiles. Strains sampled in the same site, isolated before, and after the C&D procedures and displaying the same MLST and ERIC profiles were tested for their sensitivity to different concentrations of BC, in a time course assay. The expression of non-specific efflux pumps was evaluated at each time point by qPCR using tufA gene as housekeeping. A differential expression of the two investigated genes was observed: lde was found to be more expressed by the strains isolated before C&D procedures while its expression was dose-dependent in the case of the post C&D procedures strain. On the contrary, the expression of mdrL was inhibited under low biocidal stress (10 ppm BC) and enhanced in the presence of high stress (100 ppm BC). These findings suggests a possible role for C&D procedures to select L. monocytogenes persisters, pointing out the importance of dealing with the identification of risk factors in food plants sanification procedures that might select more tolerant strains. PMID:27807430

Simultaneous enhancement of phenolic compound degradations by Acinetobacter strain V2 via a step-wise continuous acclimation process.

PubMed

Lin, Johnson; Sharma, Vikas; Milase, Ridwaan; Mbhense, Ntuthuko

2016-06-01

Phenol degradation enhancement of Acinetobacter strain V2 by a step-wise continuous acclimation process was investigated. At the end of 8 months, three stable adapted strains, designated as R, G, and Y, were developed with the sub-lethal concentration of phenol at 800, 1100, and 1400 mg/L, respectively, from 400 mg/L of V2 parent strain. All strains degraded phenol at their sub-lethal level within 24 h, their growth rate increased as the acclimation process continued and retained their degradation properties even after storing at -80 °C for more than 3 years. All adapted strains appeared coccoid with an ungranulated surface under electron microscope compared to typical rod-shaped parental strain V2 . The adapted Y strain also possessed superior degradation ability against aniline, benzoate, and toluene. This study demonstrated the use of long term acclimation process to develop efficient and better pollutant degrading bacterial strains with potentials in industrial and environmental bioremediation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goven, A.J.; Fitzpatrick, L.C.; Venables, B.J.

Understanding the toxic potential and mechanisms of action of environmental xenobiotics is fundamental for assessing risk to public and environmental health. Current established protocols with earthworms focus primarily on defining the lethal effects of chemicals associated with soil contamination. Development of sublethal assays, until recently, has been largely ignored. Here the authors develop rationale for use of earthworms as a model organism for comprehensive assessment of risks to higher wildlife from contaminated soils and hazardous waste sites. They present a panel of lethal (LC/LD50`s) and sublethal measurement endpoint biomarkers, developed within the framework of the National Toxicology Program`s tiered immunotoxicitymore » protocol for mice and according to published criteria for good measurement endpoints, that represent sensitive phylogenetically-conserved processes. Specifically the authors discuss immunosuppressive effects of terrestrial heavy metal and organic contamination on the innate, nonspecific and specific immune responses of earthworm, Lumbricus terrestris, coelomocytes in terms of total and differential cell counts, lysozyme activity, nitroblue tetrazolium dye reduction, phagocytic activity and secretary rosette formation. Findings indicate that sensitive phylogenetically conserved immune responses present in invertebrates can be used to assess or predict risk to wildlife from contaminated soils.« less

Immunophenotyping and activation status of maternal peripheral blood leukocytes during pregnancy and labour, both term and preterm.

PubMed

Zhang, Jianhong; Shynlova, Oksana; Sabra, Sally; Bang, Annie; Briollais, Laurent; Lye, Stephen J

2017-10-01

The onset of labour in rodents and in humans is associated with physiological inflammation which is manifested by infiltration of activated maternal peripheral leukocytes (mPLs) into uterine tissues. Here, we used flow cytometry to immunophenotype mPLs throughout gestation and labour, both term and preterm. Peripheral blood was collected from non-pregnant women and pregnant women in the 1st, 2nd and 3rd trimesters. Samples were also collected from women in active labour at term (TL) or preterm (PTL) and compared with women term not-in-labour (TNIL) and preterm not-in-labour (PTNIL). Different leukocyte populations were identified by surface markers such as CD45, CD14, CD15, CD3, CD4, CD8, CD19 and CD56. Their activation status was measured by the expression levels of CD11b, CD44, CD55, CD181 and CD192 proteins. Of all circulating CD45+ leukocytes, we detected significant increases in CD15+ granulocytes (i) in pregnant women versus non-pregnant; (ii) in TL women versus TNIL and versus pregnant women in the 1st/2nd/3rd trimester; (iii) in PTL women versus PTNIL. TL was characterized by (iv) increased expressions of CD11b, CD55 and CD192 on granulocytes; (v) increased mean fluorescent intensity (MFI) of CD55 and CD192 on monocytes; (vi) increased CD44 MFI on CD3+ lymphocytes as compared to late gestation. In summary, we have identified sub-populations of mPLs that are specifically activated in association with gestation (granulocytes) or with the onset of labour (granulocytes, monocytes and lymphocytes). Additionally, beta regression analysis created a set of reference values to rank this association between immune markers of pregnancy and to identify activation status with potential prognostic and diagnostic capability. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Acute toxicity assessment of Polish (waste) water with a microplate-based Hydra attenuata assay: a comparison with the Microtox test.

PubMed

Pardos, M; Benninghoff, C; Guéguen, C; Thomas, R; Dobrowolski, J; Dominik, J

1999-12-15

The use of Hydra attenuata in acute toxicity assessment is a potentially useful tool in (waste) water biomonitoring. The purpose of this study was to compare the sensitivity of H. attenuata with the extensively used Microtox test on 14 (waste) water samples from the Kraków region (South Poland). To this end, specific morphological changes displayed by the freshwater cnidarian Hydra attenuata (lethal LC50s and sublethal EC50s effects) and bioluminescence of the marine bacteria Vibrio fisheri (Microtox) were compared. Clearly, the Hydra assay was the more sensitive indicator of toxicity. No relationship was found among Hydra toxicological responses and water levels of As, Cd, Co, Cu, Pb and Zn. However, it appeared that toxicity to Hydra might be due to ammonia levels. Additional studies to better circumscribe the tolerance of H. attenuata to 'natural' water characteristics are needed.

Metals, Parasites, and Environmental Conditions Affecting Breeding Populations of Spotted Salamanders (Ambystoma maculatum) in Northern Arkansas, USA.

PubMed

DeMali, Heather M; Trauth, Stanley E; Bouldin, Jennifer L

2016-06-01

The spotted salamander (Ambystoma maculatum) is indigenous to northern Arkansas, and several breeding sites are known to exist in the region. Spotted salamanders (n = 17) were collected and examined for parasites and only three females harbored nematodes (Physaloptera spp.). Chronic aquatic bioassays were conducted using water collected from eight breeding ponds during different hydroperiod events. No lethal or sublethal effects were measured in Ceriodaphnia dubia; however, decreased growth and survival were seen in Pimephales promelas. Aqueous, sediment, and salamander hepatic samples were analyzed for As, Cd, Cu, Pb, and Ni. Metal analysis revealed possible increased metal exposure following precipitation, with greatest metal concentrations measured in sediment samples. Hepatic metal concentrations were similar in parasitized and non-parasitized individuals, and greatest Pb concentrations were measured following normal precipitation events. Determining environmental stressors of amphibians, especially during their breeding and subsequent larval life stage, is imperative to improve species conservation.

HSP70 expression in Biomphalaria glabrata snails exposed to cadmium.

PubMed

da Silva Cantinha, Rebeca; Borrely, Sueli Ivone; Oguiura, Nancy; de Bragança Pereira, Carlos Alberto; Rigolon, Marcela M; Nakano, Eliana

2017-06-01

In this study, the effects of the heavy metal cadmium on the stress protein HSP70 are investigated in freshwater mollusks Biomphalaria glabrata. Adult snails were exposed for 96h to CdCl 2 at concentrations ranging from 0.09 to 0.7mgL -1 (LC 50/96h =0.34 (0.30-0.37). Time and concentration-dependent increases in the expression of HSP70 were observed at sub-lethal levels in the immunoblotting assay. Further, an increased survival to a lethal heat shock was observed in animals pre-exposed to a nonlethal concentration of cadmium, evidencing the induction of acquired tolerance. The present study demonstrated the inducibility of B. glabrata HSP70 by cadmium, a relevant environmental contaminant, at non-lethal levels, providing evidences that the assessment of HSP70 in B. glabrata can be regarded as a suitable biomarker for ecotoxicological studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of DDT on bobwhite quail adrenal gland

USGS Publications Warehouse

Lehman, J.W.; Peterle, T.J.; Mulls, C.M.

1974-01-01

A wide range of responses to sublethal levels of DDT exist, many of which are species specific and vary within each species depending upon age, sex, and physiological state. Sublethal levels of DDT do cause an increase in the adrenal cortical tissue of bobwhite quail, which may cause increased secretion of corticosteroids, and in turn affect reproduction. A delicate homeostatic balance exists within the avian endocrine system which may be disturbed by feeding sublethal levels of chlorinated hydrocarbon pesticides. This adverse effect on the endocrine system may cause subtle reproductive failures which go unnoticed until the population is greatly reduced.

Behavioral effects of sublethal exposure to a combination of β-cyfluthrin and imidacloprid in the bed bug, Cimex lectularius L.

PubMed

Crawley, Sydney E; Kowles, Katelyn A; Gordon, Jennifer R; Potter, Michael F; Haynes, Kenneth F

2017-03-01

Bed bugs (Cimex lectularius) are blood-feeding insect pests with public health relevance. Their rapid evolution of resistance to pyrethroids has prompted a shift to combination products that include both a pyrethroid and neonicotinoid insecticide. Insecticides have both a direct impact on mortality and an indirect effect on behavior. Thus, we assessed the sublethal effects of a widely used combination product containing β-cyfluthrin (a pyrethroid) and imidacloprid (a neonicotinoid), as unexpected behavioral changes after exposure have been known to affect efficacy of insecticides. We found that bed bugs exposed to sublethal doses of a combination product containing β-cyfluthrin and imidacloprid did not feed as effectively as untreated bugs. Their locomotion behavior was also reduced. However, aggregation in response to the presence of conspecific harborages was not affected by sublethal exposure. Bed bugs exhibit behavioral changes after sublethal exposure to a combination product that could affect pest management choices and outcomes. A reduction in host-finding efficiency and feeding could complement the lethal effects of the insecticide. Alternatively, reduced locomotion following exposure could limit ongoing contact with insecticide deposits. However, an overall reduction in movement indicates that treatments are unlikely to cause dispersal of bugs to adjacent dwellings. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

TUBERCULOSIS AND LETHAL AS WELL AS SUBLETHAL WHOLE-BODY X-RAY IRRADIATION OF GUINEA PIGS (in German)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gabler, E.

1964-02-01

Lethally total-body-x-ray-irradiated (550 r) and simultaneously Tb- infected guinea pigs died earlier (1.5 to 3.2 days) than lethally irradiated control animals. A tuberculous focus formation could not be found microscopically or macroscopically in these guinea pigs or in sublethally irradiated and simultaneously infected animals. However, in tubcrculous control animals, which were killed at this time, specific foci could be found in liver, spleen, and lungs. Using sublethal irradiation (300 r) and simultaneous Tb inoculation half of the animals died a radiation death and the rest died of tuberculosis. It was found that 86.4% of the animals die a radiation deathmore » and 13.5% because of tuberculosis when irradiated sublethally 30 days after infection. The greatest tuberculosis foci in these animais appeared in lungs, spleen, and especially in the liver ( destroyed iiver''). Tuberculous giant cells of the Langhans-type were missing in case of irradiation and simultaneous tuberculosis. They appeared again about 20 to 30 days after irradiation. The native resistance to tuberculosis was very reduced in cases of simultaneous exposure; radioinduced cell shortage and cell damage permit tuberculous focus formation only after overcoming the acute radiation syndrome in case of sublethal irradiations. (auth)« less

Sex-Specific Sub-Lethal Effects and Immune Response in Ceratitis capitata Wied. (Diptera: Tephritidae) Challenged with Spinosad.

PubMed

Mura, Maria Elena; Ruiu, Luca

2018-06-21

The main objective of this study was to investigate the effects of the insecticidal compound spinosad on the survival, reproduction, and immune functions of the Mediterranean fruit fly. The lethal and sub-lethal effects were determined on Ceratitis capitata Wied. (Diptera: Tephritidae) challenged with different concentrations of spinosad. A median lethal concentration of 0.28 ppm was observed on flies feeding for 5 days on a treated diet. A significant and concentration-dependent decrease in fecundity, egg hatch rate, and lifespan was also detected in treated compared with control flies. Gene expression analyses conducted on treated insects by RT-qPCR revealed an immunomodulatory action of sub-lethal concentrations of spinosad. Target transcripts included several genes involved in medfly immunity and male or female reproductive functions. While a significant upregulation was detected in treated males a short time after spinosad ingestion, most target genes were downregulated in treated females. Our study confirmed the high toxicity of spinosad to C. capitata , highlighting an indirect effect on insect lifespan and reproductive performance at sub-lethal doses. In addition to defining the acute and sub-lethal toxicity of spinosad against the fly, this study provides new insights on the interaction of this compound with insect physiology.

Lethal and sublethal effects of chlorantraniliprole on Spodoptera cosmioides (Lepidoptera: Noctuidae).

PubMed

Lutz, Alejandra L; Bertolaccini, Isabel; Scotta, Roberto R; Curis, María C; Favaro, María A; Fernandez, Laura N; Sánchez, Daniel E

2018-05-16

Spodoptera cosmioides (Walker, 1858) population has increased in Bt soybean crops in Argentina. As there are no registered products for its control, the recommended insecticides for S. frugiperda are used. The aim of this study was therefore to determine the lethal concentration (LC) and sublethal effects of chlorantraniliprole on the biological and reproductive functions of S. cosmioides, an emerging soybean pest in Argentina. An ingestion toxicity bioassay showed that chlorantraniliprole was active against larvae of the second instar, and after 48 h exposure LC50 was 0.054 μg/ml H2O. In the study of sublethal effect, chlorantraniliprole induced changes in the life cycle of exposed S. cosmioides, which required more time to complete all stages of development (larval, pupal and adult stages). Pupal weight was also higher in larvae exposed to sublethal concentrations of chlorantraniliprole. Adult fecundity was decreased: the number of eggs laid by each adult female moth, as compared to control females, was two (LC 15 ) and eight (LC 30 ) times smaller. These results indicate that chlorantraniliprole has toxicity against S. cosmioides larvae. Sublethal effects on the biological and reproductive performance of this species can help optimize integrated pest management programs. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Sublethal Effects of Insecticide Exposure on Megacopta cribraria (Fabricius) Nymphs: Key Biological Traits and Acetylcholinesterase Activity.

PubMed

Miao, Jin; Reisig, Dominic D; Li, Guoping; Wu, Yuqing

2016-01-01

Megacopta cribraria F. (Hemiptera: Plataspidae), the kudzu bug, is an invasive insect pest of U.S. soybean. At present, insecticide application is the primary and most effective control option for M. cribraria In this study, the potential effects of sublethal and low-lethal concentrations (LC10 and LC40) of three common insecticides on key biological traits and acetylcholinesterase (AChE) activity of the treated nymphal stage of insect were assessed. The results show that the sublethal concentration of imidacloprid significantly reduced adult emergence rate of M. cribraria A low-lethal concentration of imidacloprid significantly increased nymphal development time, but significantly decreased adult emergence rate and adult longevity. Both sublethal and low-lethal concentrations of acephate caused an increase in nymphal development time and a reduction in adult emergence rate and adult longevity. Fecundity of females was significantly reduced only by exposure to low-lethal concentrations of acephate. Sublethal and low-lethal concentrations of bifenthrin increased nymphal development time, but significantly decreased adult emergence rate. In addition, we found that the AChE activity of M. cribraria was significantly increased only by LC40 imidacloprid, but strongly inhibited by acephate. © The Author 2016. Published by Oxford University Press on behalf of the Entomological Society of America.

Sub-lethal oxidative stress induces lysosome biogenesis via a lysosomal membrane permeabilization-cathepsin-caspase 3-transcription factor EB-dependent pathway.

PubMed

Leow, San Min; Chua, Shu Xian Serene; Venkatachalam, Gireedhar; Shen, Liang; Luo, Le; Clement, Marie-Veronique

2017-03-07

Here we provide evidence to link sub-lethal oxidative stress to lysosome biogenesis. Exposure of cells to sub-lethal concentrations of exogenously added hydrogen peroxide resulted in cytosol to nuclear translocation of the Transcription Factor EB (TFEB), the master controller of lysosome biogenesis and function. Nuclear translocation of TFEB was dependent upon the activation of a cathepsin-caspase 3 signaling pathway, downstream of lysosomal membrane permeabilization and accompanied by a significant increase in lysosome numbers as well as induction of TFEB-dependent lysosome-associated genes expression such as Ctsl, Lamp2 and its spliced variant Lamp2a, Neu1and Ctsb and Sqstm1 and Atg9b. The effects of sub-lethal oxidative stress on lysosomal gene expression and biogenesis were rescued upon gene silencing of caspase 3 and TFEB. Notably, caspase 3 activation was not associated with phenotypic hallmarks of apoptosis, evidenced by the absence of caspase 3 substrate cleavage, such as PARP, Lamin A/C or gelsolin. Taken together, these data demonstrate for the first time an unexpected and non-canonical role of a cathepsin-caspase 3 axis in the nuclear translocation of TFEB leading to lysosome biogenesis under conditions of sub-lethal oxidative stress.

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

PubMed

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.

Contaminant Hazard Reviews (compilation)

USGS Publications Warehouse

Eisler, R.; Munro, R.E.; Loges, L.M.; Boone, K.; Paul, M.M.; Garrett, L.J.

2000-01-01

This compact disc (CD) contains the 35 reports in the Contaminant Hazard Reviews (CHR) that were published originally between 1985 and 1999 in the U.S. Department of the Interior Biological Report series. The CD was produced because printed supplies of these reviews--a total of 105,000--became exhausted and demand remained high. Each review was prepared at the request of environmental specialists of the U.S. Fish and Wildlife Service and each contained specific information on the following: mirex, cadmium, carbofuran, toxaphene, selenium, chromium, polychlorinated biphenyls, dioxins, diazinon, mercury, polycyclic aromatic hydrocarbons, arsenic, chlorpyrifos, lead, tin, index issue, pentachlorophenol, atrazine, molybdenum, boron, chlordane, paraquat, cyanide, fenvalerate, diflubenzuron, zinc, famphur, acrolein, radiation, sodium monofluoroacetate, planar PCBs, silver, copper, nickel, and a cumulative index to chemicals and species. Each report reviewed and synthesized the technical literature on a single contaminant and its effects on terrestrial plants and invertebrates, aquatic plants and animals, avian and mammalian wildlife, and other natural resources. The subtopics include contaminant sources and uses; physical, chemical, and metabolic properties; concentrations in field collections of abiotic materials and living organisms; deficiency effects, where appropriate; lethal and sublethal effects, including effects on survival, growth, reproduction, metabolism, mutagenicity, teratogenicity, and carcinogenicity; proposed criteria for the protection of human health and sensitive natural resources; and recommendations for additional research.

Freshwater Fish Sublethal Tests: A Review of the Sublethal Tests

EPA Science Inventory

Pressure on animal testing has traditionally been the purview of mammalian toxicological science, but in the past few years, more attention is given also to environmental safety. As with higher vertebrate animal alternatives, balance between reduce animal use without impairing o...

Comparative analysis of the transcriptome responses of zebrafish embryos after exposure to low concentrations of cadmium, cobalt and copper.

PubMed

Sonnack, Laura; Klawonn, Thorsten; Kriehuber, Ralf; Hollert, Henner; Schäfers, Christoph; Fenske, Martina

2018-03-01

Metal toxicity is a global environmental challenge. Fish are particularly prone to metal exposure, which can be lethal or cause sublethal physiological impairments. The objective of this study was to investigate how adverse effects of chronic exposure to non-toxic levels of essential and non-essential metals in early life stage zebrafish may be explained by changes in the transcriptome. We therefore studied the effects of three different metals at low concentrations in zebrafish embryos by transcriptomics analysis. The study design compared exposure effects caused by different metals at different developmental stages (pre-hatch and post-hatch). Wild-type embryos were exposed to solutions of low concentrations of copper (CuSO 4 ), cadmium (CdCl 2 ) and cobalt (CoSO 4 ) until 96h post-fertilization (hpf) and microarray experiments were carried out to determine transcriptome profiles at 48 and 96hpf. We found that the toxic metal cadmium affected the expression of more genes at 96hpf than 48hpf. The opposite effect was observed for the essential metals cobalt and copper, which also showed enrichment of different GO terms. Genes involved in neuromast and motor neuron development were significantly enriched, agreeing with our previous results showing motor neuron and neuromast damage in the embryos. Our data provide evidence that the response of the transcriptome of fish embryos to metal exposure differs for essential and non-essential metals. Copyright © 2017 Elsevier Inc. All rights reserved.

Sublethal Exposure to Clove and Cinnamon Essential Oils Induces Hormetic-Like Responses and Disturbs Behavioral and Respiratory Responses in Sitophilus zeamais (Coleoptera: Curculionidae).

PubMed

Haddi, Khalid; Oliveira, Eugênio E; Faroni, Lêda R A; Guedes, Daniela C; Miranda, Natalie N S

2015-12-01

Essential oils have been suggested as suitable alternatives for controlling insect pests. However, the potential adaptive responses elicited in insects for mitigating the actions of these compounds have not received adequate attention. Furthermore, as is widely reported with traditional insecticides, sublethal exposure to essential oils might induce stimulatory responses or contribute to the development of resistance strategies that can compromise the management of insect pests. The current study evaluated the locomotory and respiratory responses as well as the number of larvae per grain produced by the maize weevil, Sitophilus zeamais Motschulsky, after being sublethally exposed to the essential oils of clove, Syzygium aromaticum L., and cinnamon, Cinnamomum zeylanicum L. The essential oils showed similar insecticidal toxicity (exposure route: contact with dried residues; Clove LC95 = 3.96 [2.78-6.75] µl/cm(2); Cinnamon LC95 = 3.47 [2.75-4.73] µl/cm(2)). A stimulatory effect on the median survival time (TL50) was observed when insects were exposed to low concentrations of each oil. Moreover, a higher number of larvae per grain was produced under sublethal exposure to clove essential oil. S. zeamais avoided the treated areas (in free-choice experiments) and altered their mobility when sublethally exposed to both essential oils. The respiratory rates of S. zeamais (i.e., CO2 production) were significantly reduced under low concentrations of the essential oils. We recommend the consideration of the potential sublethal effects elicited by botanical pesticides during the development of integrated pest management programs aiming to control S. zeamais. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Interactions between Entomopathogenic Fungus, Metarhizium anisopliae and Sublethal Doses of Spinosad for Control of House Fly, Musca domestica

PubMed Central

Sharififard, M; Mossadegh, MS; Vazirianzadeh, B; Zarei-Mahmoudabadi, A

2011-01-01

Background: Metarhizium anisopliae strain IRAN 437C is one of the most virulent fungal isolates against house fly, Musca domestica. The objective of this study was to determine the interaction of this isolate with sublethal doses of spinosad against housefly. Methods: In adult bioassay, conidia of entomopathogenic fungus were applied as inoculated bait at 105 and 107 spore per gram and spinosad at 0.5, 1 and 1.5 μg (A.I.) per gram bait. In larval bioassay, conidia were applied as combination of spore with larval bedding at 106 and 108 spore per gram and spinosad at sublethals of 0.002, 0.004 and 0.006 μg (AI) per gram medium. Results: Adult mortality was 48% and 72% for fungus alone but ranged from 66–87% and 89–95% in combination treatments of 105 and 107 spore/g with sublethal doses of spinosad respectively. The interaction between 105 spore/g with sublethals exhibited synergistic effect, but in combination of 107 spore in spite of higher mortality, the interaction was additive. There was significant difference in LT50 among various treatments. LT50 values in all combination treatments were smaller than LT50 values in alone ones. Larval mortality was 36% and 69% for fungus alone but ranged from 58%–78% and 81%–100% in combination treatments of 106 and 108 spore/g medium with sublethals of spinosad respectively. The interaction was synergistic in all combination treatments of larvae. Conclusion: The interaction between M. anispliae and spinosad indicated a synergetic effect that increased the house fly mortality as well as reduced the lethal time. PMID:22808408

Early Short-Term Antiretroviral Therapy Is Associated with a Reduced Prevalence of CD8+FoxP3+ T Cells in Simian Immunodeficiency Virus-Infected Controller Rhesus Macaques

PubMed Central

George, Jeffy; Cofano, Egidio Brocca; Lybarger, Elizabeth; Louder, Mark; Lafont, Bernard A.P.; Mascola, John R.; Robert-Guroff, Marjorie

2011-01-01

Abstract Regulatory T cells contain a mix of CD4 and CD8 T cell subsets that can suppress immune activation and at the same time suppress immune responses, thereby contributing to disease progression. Recent studies have shown that an increased prevalence of CD8+FoxP3+ T regulatory cells was associated with immune suppression and diminished viral control in simian immunodeficiency virus (SIV)-infected rhesus macaques. Preventing an increase in the prevalence of CD8 T regulatory subsets is likely to lead to a better long-term outcome. Here we show that short-term antiretroviral therapy initiated within 1 week after SIV infection was associated with lower viral set point and immune activation after withdrawal of therapy as compared to untreated animals. Early short-term treated controller animals were found to have better SIV-specific immune responses and a significantly lower prevalence of immunosuppressive CD8+FoxP3+ T cells. Lower levels of CD8+FoxP3+ T cells coincided with preservation of CD4+FoxP3+ T cells at homeostatic levels, and significantly correlated with lower immune activation, suggesting a role for viral infection-driven immune activation in the expansion of CD8+FoxP3+ T cells. Interestingly, initiation of continuous therapy later in infection did not reduce the increased prevalence of CD8+FoxP3+ T cells to homeostatic levels. Taken together, our results suggest that early antiretroviral therapy preserves the integrity of the immune system leading to a lower viral set point in controller animals, and prevents alterations in the homeostatic balance between CD4+ and CD8+ T regulatory cells that could aid in better long-term outcome. PMID:21142402

A Convenient Model of Severe, High Incidence Autoimmune Gastritis Caused by Polyclonal Effector T Cells and without Perturbation of Regulatory T Cells

PubMed Central

Tu, Eric; Ang, Desmond K. Y.; Hogan, Thea V.; Read, Simon; Chia, Cheryl P. Z.; Gleeson, Paul A.; van Driel, Ian R.

2011-01-01

Autoimmune gastritis results from the breakdown of T cell tolerance to the gastric H+/K+ ATPase. The gastric H+/K+ ATPase is responsible for the acidification of gastric juice and consists of an α subunit (H/Kα) and a β subunit (H/Kβ). Here we show that CD4+ T cells from H/Kα-deficient mice (H/Kα−/−) are highly pathogenic and autoimmune gastritis can be induced in sublethally irradiated wildtype mice by adoptive transfer of unfractionated CD4+ T cells from H/Kα−/− mice. All recipient mice consistently developed the most severe form of autoimmune gastritis 8 weeks after the transfer, featuring hypertrophy of the gastric mucosa, complete depletion of the parietal and zymogenic cells, and presence of autoantibodies to H+/K+ ATPase in the serum. Furthermore, we demonstrated that the disease significantly affected stomach weight and stomach pH of recipient mice. Depletion of parietal cells in this disease model required the presence of both H/Kα and H/Kβ since transfer of H/Kα−/− CD4+ T cells did not result in depletion of parietal cells in H/Kα−/− or H/Kβ−/− recipient mice. The consistency of disease severity, the use of polyclonal T cells and a specific T cell response to the gastric autoantigen make this an ideal disease model for the study of many aspects of organ-specific autoimmunity including prevention and treatment of the disease. PMID:22096532

UVB radiation and human monocyte accessory function: Differential effects on pre-mitotic events in T-cell activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krutmann, J.K.; Kammer, G.M.; Toossi, Z.

Purified T lymphocytes fail to proliferate in response to antigenic and mitogenic stimuli when cultured in the presence of accessory cells that have been exposed in vitro to sublethal doses of UVB radiation. Because proliferation represents a final stage in the T-cell activation process, the present study was conducted to determine whether T cells were able to progress through any of the pre-mitotic stages when UVB-irradiated monocytes were used as model accessory cells. In these experiments, monoclonal anti-CD3 antibodies were employed as the mitogenic stimulus. Culture of T cells with UVB-irradiated monocytes did allow the T cells to undergo anmore » increase in intracellular free calcium, which is one of the first steps in the activation sequence. The T cells expressed interleukin-2 receptors, although at a reduced level. However, T cells failed to produce interleukin-2 above background levels when they were placed in culture with monocytes exposed to UVB doses as low as 50 J/m2. Incubation of T cells with UVB-irradiated monocytes did not affect the subsequent capacity of T cells to proliferate, since they developed a normal proliferative response in secondary culture when restimulated with anti-CD3 antibodies and unirradiated monocytes. These studies indicate that T lymphocytes become partially activated when cultured with UVB-irradiated monocytes and mitogenic anti-CD3 monoclonal antibodies. In addition, they suggest that interleukin-2 production is the T-cell activation step most sensitive to inhibition when UVB-irradiated monocytes are employed as accessory cells.« less

Preterm Cord Blood Contains a Higher Proportion of Immature Hematopoietic Progenitors Compared to Term Samples

PubMed Central

Podestà, Marina; Bruschettini, Matteo; Cossu, Claudia; Sabatini, Federica; Dagnino, Monica; Romantsik, Olga; Spaggiari, Grazia Maria; Ramenghi, Luca Antonio; Frassoni, Francesco

2015-01-01

Background Cord blood contains high number of hematopoietic cells that after birth disappear. In this paper we have studied the functional properties of the umbilical cord blood progenitor cells collected from term and preterm neonates to establish whether quantitative and/or qualitative differences exist between the two groups. Methods and Results Our results indicate that the percentage of total CD34+ cells was significantly higher in preterm infants compared to full term: 0.61% (range 0.15–4.8) vs 0.3% (0.032–2.23) p = 0.0001 and in neonates <32 weeks of gestational age (GA) compared to those ≥32 wks GA: 0.95% (range 0.18–4.8) and 0.36% (0.15–3.2) respectively p = 0.0025. The majority of CD34+ cells co-expressed CD71 antigen (p<0.05 preterm vs term) and grew in vitro large BFU-E, mostly in the second generation. The subpopulations CD34+CD38- and CD34+CD45- resulted more represented in preterm samples compared to term, conversely, Side Population (SP) did not show any difference between the two group. The absolute number of preterm colonies (CFCs/10microL) resulted higher compared to term (p = 0.004) and these progenitors were able to grow until the third generation maintaining an higher proportion of CD34+ cells (p = 0.0017). The number of colony also inversely correlated with the gestational age (Pearson r = -0.3001 p<0.0168). Conclusions We found no differences in the isolation and expansion capacity of Endothelial Colony Forming Cells (ECFCs) from cord blood of term and preterm neonates: both groups grew in vitro large number of endothelial cells until the third generation and showed a transitional phenotype between mesenchymal stem cells and endothelial progenitors (CD73, CD31, CD34 and CD144)The presence, in the cord blood of preterm babies, of high number of immature hematopoietic progenitors and endothelial/mesenchymal stem cells with high proliferative potential makes this tissue an important source of cells for developing new cells therapies. PMID:26417990

Preterm Cord Blood Contains a Higher Proportion of Immature Hematopoietic Progenitors Compared to Term Samples.

PubMed

Podestà, Marina; Bruschettini, Matteo; Cossu, Claudia; Sabatini, Federica; Dagnino, Monica; Romantsik, Olga; Spaggiari, Grazia Maria; Ramenghi, Luca Antonio; Frassoni, Francesco

2015-01-01

Cord blood contains high number of hematopoietic cells that after birth disappear. In this paper we have studied the functional properties of the umbilical cord blood progenitor cells collected from term and preterm neonates to establish whether quantitative and/or qualitative differences exist between the two groups. Our results indicate that the percentage of total CD34+ cells was significantly higher in preterm infants compared to full term: 0.61% (range 0.15-4.8) vs 0.3% (0.032-2.23) p = 0.0001 and in neonates <32 weeks of gestational age (GA) compared to those ≥32 wks GA: 0.95% (range 0.18-4.8) and 0.36% (0.15-3.2) respectively p = 0.0025. The majority of CD34+ cells co-expressed CD71 antigen (p<0.05 preterm vs term) and grew in vitro large BFU-E, mostly in the second generation. The subpopulations CD34+CD38- and CD34+CD45- resulted more represented in preterm samples compared to term, conversely, Side Population (SP) did not show any difference between the two group. The absolute number of preterm colonies (CFCs/10microL) resulted higher compared to term (p = 0.004) and these progenitors were able to grow until the third generation maintaining an higher proportion of CD34+ cells (p = 0.0017). The number of colony also inversely correlated with the gestational age (Pearson r = -0.3001 p<0.0168). We found no differences in the isolation and expansion capacity of Endothelial Colony Forming Cells (ECFCs) from cord blood of term and preterm neonates: both groups grew in vitro large number of endothelial cells until the third generation and showed a transitional phenotype between mesenchymal stem cells and endothelial progenitors (CD73, CD31, CD34 and CD144)The presence, in the cord blood of preterm babies, of high number of immature hematopoietic progenitors and endothelial/mesenchymal stem cells with high proliferative potential makes this tissue an important source of cells for developing new cells therapies.

Impact of imidacloprid on new queens of imported fire ants, Solenopsis invicta (Hymenoptera: Formicidae)

USDA-ARS?s Scientific Manuscript database

Neonicotinoid insecticides are commonly used in managing pest ants, including the imported fire ant, Solenopsis invicta Buren. There is increasing evidence that neonicotinoid insecticides at sublethal concentrations have profound effects on social insects. However, the sublethal effect of neonicot...

Sublethal effects of pesticides on queen rearing success

USDA-ARS?s Scientific Manuscript database

The effects of sublethal pesticide exposure on queen emergence and virus titers were examined. Queen rearing colonies were fed pollen with chlorpyrifos (CPF) alone (pollen-1) and with CPF and the fungicide Pristine ® (pollen-2). Fewer queens emerged when larvae from open foraging ...

Behavioral indicators of sublethal toxicity in rainbow trout

USGS Publications Warehouse

Little, Edward E.; Archeski, Richard D.; Flerov, Boris A.; Kozlovskaya, Vera I.

1990-01-01

Four measures of behavior-spontaneous swimming activity, swimming capacity, feeding behavior, and vulnerability to predation-were assessed as indicators of sublethal toxicity in rainbow trout (Oncorhynchus mykiss) in 96-hr exposures to sublethal concentrations of six agricultural chemicals: carbaryl, chlordane, dimethylamine salt of 2,4-dichlorophenoxyacetic acid (2,4-DMA), tributyl phosphorotrithioate (DBF 1), methyl parathion, and pentachlorophenol. After exposures, behavioral changes consistently demonstrated sublethal toxicity, but effects on specific behaviors varied with contaminants and their concentrations were altered by the water quality criterion concentration for chlordane (2 μg/L), and at a concentration of DEF (5 μg/L) that had previously been shown to inhibit growth and survival after a 90-day exposure. Feeding behavior was inhibited most by exposure to DEF, 2,4-DMA, and methyl parathion. Vulnerability to predation was heightened most by exposure to carbaryl and pentachlorophenol. Although all chemicals inhibited spontaneous swimming activity, only carbaryl, DEF, and 2,4-DMA influenced swimming capacity.

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

USDA-ARS?s Scientific Manuscript database

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...

Early life exposure to PCB126 results in delayed mortality and growth impairment in the zebrafish larvae.

PubMed

Di Paolo, Carolina; Groh, Ksenia J; Zennegg, Markus; Vermeirssen, Etiënne L M; Murk, Albertinka J; Eggen, Rik I L; Hollert, Henner; Werner, Inge; Schirmer, Kristin

2015-12-01

The occurrence of chronic or delayed toxicity resulting from the exposure to sublethal chemical concentrations is an increasing concern in environmental risk assessment. The Fish Embryo Toxicity (FET) test with zebrafish provides a reliable prediction of acute toxicity in adult fish, but it cannot yet be applied to predict the occurrence of chronic or delayed toxicity. Identification of sublethal FET endpoints that can assist in predicting the occurrence of chronic or delayed toxicity would be advantageous. The present study characterized the occurrence of delayed toxicity in zebrafish larvae following early exposure to PCB126, previously described to cause delayed effects in the common sole. The first aim was to investigate the occurrence and temporal profiles of delayed toxicity during zebrafish larval development and compare them to those previously described for sole to evaluate the suitability of zebrafish as a model fish species for delayed toxicity assessment. The second aim was to examine the correlation between the sublethal endpoints assessed during embryonal and early larval development and the delayed effects observed during later larval development. After exposure to PCB126 (3-3000ng/L) until 5 days post fertilization (dpf), larvae were reared in clean water until 14 or 28 dpf. Mortality and sublethal morphological and behavioural endpoints were recorded daily, and growth was assessed at 28 dpf. Early life exposure to PCB126 caused delayed mortality (300 ng/L and 3000 ng/L) as well as growth impairment and delayed development (100 ng/L) during the clean water period. Effects on swim bladder inflation and cartilaginous tissues within 5 dpf were the most promising for predicting delayed mortality and sublethal effects, such as decreased standard length, delayed metamorphosis, reduced inflation of swim bladder and column malformations. The EC50 value for swim bladder inflation at 5 dpf (169 ng/L) was similar to the LC50 value at 8 dpf (188 and 202 ng/L in two experiments). Interestingly, the patterns of delayed mortality and delayed effects on growth and development were similar between sole and zebrafish. This indicates the comparability of critical developmental stages across divergent fish species such as a cold water marine flatfish and a tropical freshwater cyprinid. Additionally, sublethal effects in early embryo-larval stages were found promising for predicting delayed lethal and sublethal effects of PCB126. Therefore, the proposed method with zebrafish is expected to provide valuable information on delayed mortality and delayed sublethal effects of chemicals and environmental samples that may be extrapolated to other species. Copyright © 2015 Elsevier B.V. All rights reserved.

Analysis of persistent changes to γ-aminobutyric acid receptor gene expression in Plutella xylostella subjected to sublethal amounts of spinosad.

PubMed

Yin, X-H; Wu, Q-J; Zhang, Y-J; Long, Y-H; Wu, X-M; Li, R-Y; Wang, M; Tian, X-L; Jiao, X-G

2016-07-25

A multi-generational approach was used to investigate the persistent effects of a sub-lethal dose of spinosad in Plutella xylostella. The susceptibility of various sub-populations of P. xylostella to spinosad and the effects of the insecticide on the gene expression of γ-aminobutyric acid receptor (GABAR) were determined. The results of a leaf dip bioassay showed that the sensitivity of P. xylostella to spinosad decreased across generations. The sub-strains had been previously selected based on a determined LC25 of spinosad. Considering that GABA-gated chloride channels are the primary targets of spinosad, the cDNA of P. xylostella was used to clone GABARα by using reverse transcription-polymerase chain reaction (RT-PCR). The mature peptide cDNA was 1477-bp long and contained a 1449-bp open reading frame encoding a protein of 483 amino acids. The resulting amino acid sequence was used to generate a neighbor-joining dendrogram, and homology search was conducted using NCBI BLAST. The protein had high similarity with the known GABAR sequence from P. xylostella. Subsequent semi-quantitative RT-PCR and real-time PCR analyses indicated that the GABAR transcript levels in the spinosad-resistant strain (RR, 145.82-fold) and in Sub1 strain (selected with LC25 spinosad for one generation) were the highest, followed by those in the spinosad-susceptible strain, the Sub10 strain (selected for ten generations), and the Sub5 strain (selected for five generations). This multi-generational study found significant correlations between spinosad susceptibility and GABAR gene expression, providing insights into the long-term effects of sub-lethal insecticide exposure and its potential to lead to the development of insecticide-resistant insect populations.

Effect of sublethal preculturing on the survival of probiotics and metabolite formation in set-yoghurt.

PubMed

Settachaimongkon, Sarn; van Valenberg, Hein J F; Winata, Vera; Wang, Xiaoxi; Nout, M J Robert; van Hooijdonk, Toon C M; Zwietering, Marcel H; Smid, Eddy J

2015-08-01

The objective of this study was to investigate the effect of preculturing of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB12 under sublethal stress conditions on their survival and metabolite formation in set-yoghurt. Prior to co-cultivation with yoghurt starters in milk, the two probiotic strains were precultured under sublethal stress conditions (combinations of elevated NaCl and low pH) in a batch fermentor. The activity of sublethally precultured probiotics was evaluated during fermentation and refrigerated storage by monitoring bacterial population dynamics, milk acidification and changes in volatile and non-volatile metabolite profiles of set-yoghurt. The results demonstrated adaptive stress responses of the two probiotic strains resulting in their viability improvement without adverse influence on milk acidification. A complementary metabolomic approach using SPME-GC/MS and (1)H-NMR resulted in the identification of 35 volatiles and 43 non-volatile polar metabolites, respectively. Principal component analysis revealed substantial impact of the activity of sublethally precultured probiotics on metabolite formation demonstrated by distinctive volatile and non-volatile metabolite profiles of set-yoghurt. Changes in relative abundance of various aroma compounds suggest that incorporation of stress-adapted probiotics considerably influences the organoleptic quality of product. This study provides new information on the application of stress-adapted probiotics in an actual food-carrier environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multi-OMIC profiling of survival and metabolic signaling networks in cells subjected to photodynamic therapy.

PubMed

Weijer, Ruud; Clavier, Séverine; Zaal, Esther A; Pijls, Maud M E; van Kooten, Robert T; Vermaas, Klaas; Leen, René; Jongejan, Aldo; Moerland, Perry D; van Kampen, Antoine H C; van Kuilenburg, André B P; Berkers, Celia R; Lemeer, Simone; Heger, Michal

2017-03-01

Photodynamic therapy (PDT) is an established palliative treatment for perihilar cholangiocarcinoma that is clinically promising. However, tumors tend to regrow after PDT, which may result from the PDT-induced activation of survival pathways in sublethally afflicted tumor cells. In this study, tumor-comprising cells (i.e., vascular endothelial cells, macrophages, perihilar cholangiocarcinoma cells, and EGFR-overexpressing epidermoid cancer cells) were treated with the photosensitizer zinc phthalocyanine that was encapsulated in cationic liposomes (ZPCLs). The post-PDT survival pathways and metabolism were studied following sublethal (LC 50 ) and supralethal (LC 90 ) PDT. Sublethal PDT induced survival signaling in perihilar cholangiocarcinoma (SK-ChA-1) cells via mainly HIF-1-, NF-кB-, AP-1-, and heat shock factor (HSF)-mediated pathways. In contrast, supralethal PDT damage was associated with a dampened survival response. PDT-subjected SK-ChA-1 cells downregulated proteins associated with EGFR signaling, particularly at LC 90 . PDT also affected various components of glycolysis and the tricarboxylic acid cycle as well as metabolites involved in redox signaling. In conclusion, sublethal PDT activates multiple pathways in tumor-associated cell types that transcriptionally regulate cell survival, proliferation, energy metabolism, detoxification, inflammation/angiogenesis, and metastasis. Accordingly, tumor cells sublethally afflicted by PDT are a major therapeutic culprit. Our multi-omic analysis further unveiled multiple druggable targets for pharmacological co-intervention.

Long-Term Cultured Human Term Placenta-Derived Mesenchymal Stem Cells of Maternal Origin Displays Plasticity

PubMed Central

Sabapathy, Vikram; Ravi, Saranya; Srivastava, Vivi; Srivastava, Alok; Kumar, Sanjay

2012-01-01

Mesenchymal stem cells (MSCs) are an alluring therapeutic resource because of their plasticity, immunoregulatory capacity and ease of availability. Human BM-derived MSCs have limited proliferative capability, consequently, it is challenging to use in tissue engineering and regenerative medicine applications. Hence, placental MSCs of maternal origin, which is one of richest sources of MSCs were chosen to establish long-term culture from the cotyledons of full-term human placenta. Flow analysis established bonafied MSCs phenotypic characteristics, staining positively for CD29, CD73, CD90, CD105 and negatively for CD14, CD34, CD45 markers. Pluripotency of the cultured MSCs was assessed by in vitro differentiation towards not only intralineage cells like adipocytes, osteocytes, chondrocytes, and myotubules cells but also translineage differentiated towards pancreatic progenitor cells, neural cells, and retinal cells displaying plasticity. These cells did not significantly alter cell cycle or apoptosis pattern while maintaining the normal karyotype; they also have limited expression of MHC-II antigens and are Naive for stimulatory factors CD80 and CD 86. Further soft agar assays revealed that placental MSCs do not have the ability to form invasive colonies. Taking together all these characteristics into consideration, it indicates that placental MSCs could serve as good candidates for development and progress of stem-cell based therapeutics. PMID:22550499

Modulation of ionizing radiation-induced apoptosis and cell cycle arrest by all-trans retinoic acid in promyelocytic leukemia cells (HL-60).

PubMed

Mareková, M; Vávrová, J; Vokurková, D; Psutka, J

2003-01-01

Acute promyelocytic leukemia is characterized by a block of myeloid differentiation. The incubation of cells with 1 micromol/l all-trans retinoic acid (ATRA) for 72 h induced differentiation of HL-60 cells and increased the number of CD11b positive cells. Morphological and functional changes were accompanied by a loss of proliferative capacity. Differentiation caused by preincubation of leukemic cells HL-60 with ATRA is accompanied by loss of clonogenicity (control cells: 870 colonies/10(3) cells, cells preincubated with ATRA: 150 colonies/10(3) cells). D0 for undifferentiated cells was 2.35 Gy, for ATRA differentiated cells 2.46 Gy. Statistical comparison of clonogenity curves indicated that in the whole range 0.5-10 Gy the curves are not significantly different, however, in the range 0.5-3 Gy ATRA differentiated cells were significantly more radioresistant than non-differentiated cells. When HL-60 cells preincubated with 1 micromol/l ATRA were irradiated by a sublethal dose of 6 Gy, more marked increase of apoptotic cells number was observed 24 h after irradiation and the surviving cells were mainly in the G1 phase of the cell cycle, while only irradiated cells were accumulated in G(2) phase. Our results imply that preincubation of cells with ATRA accelerates apoptosis occurrence (24 h) after irradiation by high sublethal dose of 6 Gy. Forty-eight hours after 6 Gy irradiation, late apoptotic cells were found in the group of ATRA pretreated cells, as determined by APO2.7 positivity. This test showed an increased effect (considering cell death induction) in comparison to ATRA or irradiation itself.

Short-Term Exposure to Lambda-Cyhalothrin Negatively Affects the Survival and Memory-Related Characteristics of Worker Bees Apis mellifera.

PubMed

Liao, Chun-Hua; He, Xu-Jiang; Wang, Zi-Long; Barron, Andrew B; Zhang, Bo; Zeng, Zhi-Jiang; Wu, Xiao-Bo

2018-07-01

Pesticides are considered one of the major contemporary stressors of honey bee health. In this study, the effects of short-term exposure to lambda-cyhalothrin on lifespan, learning, and memory-related characteristics of Apis mellifera were systematically examined. Short-term exposure to lambda-cyhalothrin in worker bees reduced lifespan, affected learning and memory performance, reduced the homing ability, and influenced the expression levels of two learning and memory-related genes of A. mellifera. This research identifies the nature of the sublethal effects of lambda-cyhalothrin on bees and the level of exposure that can be harmful to bee health. This new information will assist in establishing guidelines for the safe use of lambda-cyhalothrin in the field.

Monitoring colony-level effects of sublethal pesticide exposure on honey bees

USDA-ARS?s Scientific Manuscript database

The effects of sublethal pesticide exposure to honey bee colonies may be significant but difficult to detect in the field using standard visual assessment methods. Here we describe methods to measure the quantities of adult bees, brood and food resources by weighing hives and hive parts, by photogra...

EFFECTS OF SUBLETHAL X-RAY DOSES ON ORGANS WITH HIGH RADIATION SENSITIVITY ESPECIALLY ON FEMALE GENITAL GLANDS AND ON FOETUSES IN UTERO

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trautmann, J.

1961-01-01

S>The effects of small radiation doses are reviewed. Changes in organs of mice and rabbits after irradiation with sublethal doses are studied. Damages in female genital glands and fetuses of mice are investigated. (Gmelin Inst.)

CD40-CD40 Ligand Pathway is a Major Component of Acute Neuroinflammation and Contributes to Long-term Cognitive Dysfunction after Sepsis.

PubMed

Michels, Monique; Danieslki, Lucinéia Gainski; Vieira, Andriele; Florentino, Drielly; Dall'Igna, Dhébora; Galant, Letícia; Sonai, Beatriz; Vuolo, Francieli; Mina, Franciele; Pescador, Bruna; Dominguini, Diogo; Barichello, Tatiana; Quevedo, João; Dal-Pizzol, Felipe; Petronilho, Fabrícia

2015-03-26

Sepsis-associated encephalopathy (SAE) is associated with an increased rate of morbidity and mortality. It is not understood what the exact mechanism is for the brain dysfunction that occurs in septic patients, but brain inflammation and oxidative stress are a possible theory. Such events can occur through the alteration of molecules that perpetuate the inflammatory response. Thus, it is possible to postulate that CD40 may be involved in this process. The aim of this work is to evaluate the role of CD40-CD40L pathway activation in brain dysfunction associated with sepsis in an animal model. Microglia activation induces the upregulation of CD40-CD40L, both in vitro and in vivo. The inhibition of microglia activation decreases levels of CD40-CD40L in the brain and decreases brain inflammation, oxidative damage and blood brain barrier dysfunction. Despite this, anti-CD40 treatment does not improve mortality in this model. However, it is able to improve long-term cognitive impairment in sepsis survivors. In conclusion, there is a major involvement of the CD40-CD40L signaling pathway in long-term brain dysfunction in an animal model of sepsis.

CD40–CD40 Ligand Pathway Is a Major Component of Acute Neuroinflammation and Contributes to Long-term Cognitive Dysfunction after Sepsis

PubMed Central

Michels, Monique; Danieslki, Lucinéia Gainski; Vieira, Andriele; Florentino, Drielly; Dall’Igna, Dhébora; Galant, Letícia; Sonai, Beatriz; Vuolo, Francieli; Mina, Franciele; Pescador, Bruna; Dominguini, Diogo; Barichello, Tatiana; Quevedo, João; Dal-Pizzol, Felipe; Petronilho, Fabrícia

2015-01-01

Sepsis-associated encephalopathy (SAE) is associated with an increased rate of morbidity and mortality. It is not understood what the exact mechanism is for the brain dysfunction that occurs in septic patients, but brain inflammation and oxidative stress are a possible theory. Such events can occur through the alteration of molecules that perpetuate the inflammatory response. Thus, it is possible to postulate that CD40 may be involved in this process. The aim of this work is to evaluate the role of CD40–CD40L pathway activation in brain dysfunction associated with sepsis in an animal model. Microglia activation induces the upregulation of CD40–CD40L, both in vitro and in vivo. The inhibition of microglia activation decreases levels of CD40–CD40L in the brain and decreases brain inflammation, oxidative damage and blood brain barrier dysfunction. Despite this, anti-CD40 treatment does not improve mortality in this model. However, it is able to improve long-term cognitive impairment in sepsis survivors. In conclusion, there is a major involvement of the CD40–CD40L signaling pathway in long-term brain dysfunction in an animal model of sepsis. PMID:25822797

Modeling marrow damage from response data: Evolution from radiation biology to benzene toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, T.D.; Morris, M.D.; Hasan, J.S.

1996-12-01

Consensus principles from radiation biology were used to describe a generic set of nonlinear, first-order differential equations for modeling toxicity-induced compensatory cell kinetics in terms of sublethal injury, repair, direct killing, killing of cells with unrepaired sublethal injury, and repopulation. This cellular model was linked to a probit model of hematopoietic mortality that describes death from infection and/or hemorrhage between 5 and 30 days. Mortality data from 27 experiments with 851 dose-response groups, in which doses were protracted by rate and/or fractionation, were used to simultaneously estimate all rate constants by maximum-likelihood methods. Data used represented 18,940 test animals: 12,827more » mice, 2925 rats, 1676 sheep, 829 swine, 479 dogs, and 204 burros. Although a long-term, repopulating hematopoietic stem cell is ancestral to all lineages needed to restore normal homeostasis, the dose-response data from the protracted irradiations indicate clearly that the particular lineage that is critical to hematopoietic recovery does not resemble stemlike cells with regard to radiosensitivity and repopulation rates. Instead, the weakest link in the chain of hematopoiesis was found to have an intrinsic radioresistance equal to or greater than stromal cells and to repopulate at the same rates. Model validation has been achieved by predicting the LD50 and/or fractional group mortality in 38 protracted-dose experiments (rats and mice) that were not used in the fitting of model coefficients. 29 refs., 5 figs., 5 tabs.« less

Incomplete Recovery of CD4 count, CD4 Percentage, and CD4/CD8 ratio in HIV-Infected Patients on Long-Term Antiretroviral Therapy with Suppressed Viremia.

PubMed

Mutoh, Yoshikazu; Nishijima, Takeshi; Inaba, Yosuke; Tanaka, Noriko; Kikuchi, Yoshimi; Gatanaga, Hiroyuki; Oka, Shinichi

2018-03-02

The extent and duration of long-term recovery of CD4 count, CD4%, and CD4/CD8 ratio after initiation of combination antiretroviral therapy (cART) in patients with suppressed viral load are largely unknown. HIV-1 infected patients who started cART between January 2004 and January 2012 and showed persistent viral suppression (<200 copies/mL) for at least 4 years were followed up at AIDS Clinical Center, Tokyo. Change point analysis was used to determine the time point where CD4 count recovery shows a plateau, and linear mixed model was applied to estimate CD4 count at the change point. Data of 752 patients were analyzed [93% males, median age 38, median baseline CD4 count 172/µL (IQR, 62-253), CD4% 13.8% (IQR, 7.7-18.5), and CD4/8 ratio 0.23 (IQR, 0.12-0.35)]. The median follow-up period was 81.2 months and 91 (12.1%) patients were followed for >10 years. Change point analysis showed that CD4 count, CD4%, and CD4/CD8 ratio, continued to increase until 78.6, 62.2, and 64.3 months, respectively, with adjusted mean of 590 /µL (95%CI 572-608), 29.5% (29-30.1), and 0.89 (0.86-0.93), respectively, at the change point. Although 73.8% of the study patients achieved CD4 count ≥500 /μL, 48.2% of the patients with baseline CD4 count <100 /μL did not achieve CD4 count ≥500 /μL. Neither CD4% nor CD4/CD8 ratio normalized in a majority of patients. The results showed lack of normalization of CD4 count, CD4%, and CD4/CD8 ratio to the levels seen in healthy individuals even after long-term successful cART in patients with suppressed viral load.

Central memory CD4 T cells are associated with incomplete restoration of the CD4 T cell pool after treatment-induced long-term undetectable HIV viraemia.

PubMed

Rallón, Norma; Sempere-Ortells, José M; Soriano, Vincent; Benito, José M

2013-11-01

It is unclear to what extent T cell reconstitution may be possible in HIV-1-infected individuals on continuous successful highly active antiretroviral therapy (HAART). Herein, we analysed distinct phenotypic markers of immune recovery in patients with undetectable viraemia for 8 years, taking as reference untreated patients and healthy controls. Seventy-two subjects were examined: 28 HIV-1+ patients on successful long-term HAART, 24 HIV-1+ untreated viraemic patients and 20 age-matched healthy controls. Analysis of naive and memory CD4 and CD8 T cells was combined with measurements of activation status (expression of CD38) and with thymic function (expression of CD31). Statistical significance was determined by non-parametric tests. After long-term HAART, the majority of parameters were normalized compared with age-matched control values, including T cell activation and thymic function. However, absolute counts of naive and central memory CD4 T cells remained below normal levels. The only parameters significantly associated with CD4 counts at the end of follow-up were the pre-HAART CD4 count ( β ± SD = 0.54 ± 0.16, P = 0.003) and the level of CD4 central memory cells at the end of follow-up (β ± SD = 1.18 ± 0.23, P < 0.0001). Only patients starting HAART with CD4 counts >350 cells/mm(3) reached a complete normalization of CD4 counts. Even after long-term successful HAART, complete CD4 restoration may be attainable only in patients starting therapy with moderately high CD4 counts, prompting early initiation of antiretroviral therapy. Incomplete CD4 restoration may be associated with a defective restoration of central memory CD4 T cells, a cell subset with a pivotal role in T cell homeostasis.

Toxic effects of selenium and copper on the planarian, Dugesia dorotocephala

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rauscher, J.D.

1988-01-01

Aquatic toxicologists have become increasingly concerned with the effects of sublethal concentrations of toxicants on aquatic organisms. Sublethal effects of toxicants on freshwater invertebrates were reviewed. Selenium (Se) and copper (Cu) are both essential trace elements and toxicants. Se has been reported to alter the toxicity of heavy metals. Planarians, Dugesia dorotocephala, were used as test animals. The objectives of this study were to determine: (1) acute toxicity of Se on planarians and the effect of the number of planarians per test chamber, (2) interaction of the acute toxicity of Se and Cu on planarians, and (3) sublethal effects ofmore » Se and Cu on planarians.« less

A COMPARISON OF THE LETHAL AND SUBLETHAL TOXICITY OF ORGANIC CHEMICAL MIXTURES TO THE FATHEAD MINNOW (PIMEPHALES PROMELAS)

EPA Science Inventory

This study was designed to define the degree of concentration addition found for mixtures of certain xenobiotics that are thought to act through a similar or different mode of toxic action for the acute mortality and sublethal growth toxicity endpoints, and for a freshwater fish ...

Assessment of chronic sublethal effects of imidacloprid on honey bee colony health

USDA-ARS?s Scientific Manuscript database

Here we present results of a three-year study to determine the fate of imidacloprid residues in hive matrices and to assess chronic sublethal effects on whole honey bee colonies fed supplemental pollen diet containing imidacloprid at 5, 20 and 100 µg/kg over multiple brood cycles. Various endpoints ...

Sublethal effects of Imidacloprid on honey bee colony growth and activity at three sites in the U.S.

USDA-ARS?s Scientific Manuscript database

Field experiments in southern Arizona, central Arkansas and southern Mississippi were conducted to evaluate the effects of sublethal concentrations (0, 5, 20 and 100 ppb) of imidacloprid in sugar syrup on honey bee colony growth and activity. Response variables included discrete data from hive inspe...

Low, medium and high heat tolerant strains of Listeria monocytogenes and increased heat stress resistance after exposure to sublethal heat

USDA-ARS?s Scientific Manuscript database

Listeria monocytogenes exhibits sophisticated adaptive mechanisms to counteract higher levels of lethal acid, heat, salt or oxidative stresses after pre-exposure to sublethal concentrations of homogenous stress. A group of 37 strains representing all 13 serotypes of Listeria monocytogenes with initi...

Behavioural sensitivity of a key Southern Ocean species (Antarctic krill, Euphausia superba) to p,p'-DDE exposure.

PubMed

Poulsen, Anita H; Kawaguchi, So; King, Catherine K; King, Robert A; Bengtson Nash, Susan M

2012-01-01

Persistent organic pollutants (POPs) have been frequently measured throughout the Southern Ocean food web for which little information is available to assess the potential risks of POP exposure. The current study evaluated the toxicological sensitivity of a key Southern Ocean species, Antarctic krill, to aqueous exposure of p,p'-dichlorodiphenyl dichloroethylene (p,p'-DDE). Behavioural endpoints were used as indicators of sublethal toxicity. Immediate behavioural responses (partial immobility and tail flicking) most likely reflect neurotoxicity, while the p,p'-DDE body residue causing a median level of sublethal toxicity in Antarctic krill following 96h exposure (IEC50(sublethal toxicity)=3.9±0.21mmol/kg lipid weight) is comparable to those known to cause sublethal narcosis in temperate aquatic species. Critical body residues (CBRs) were more reproducible across tests than effective seawater concentrations. These findings support the concept of the CBR approach, that effective tissue residues are comparable across species and geographical ranges despite differences in environmental factors. Copyright © 2011 Elsevier Inc. All rights reserved.

Quantification of midkine gene expression in Patella caerulea (Mollusca, Gastropoda) exposed to cadmium

NASA Astrophysics Data System (ADS)

Stillitano, Francesca; Mugelli, Alessandro; Cerbai, Elisabetta; Vanucci, Silvana

2007-10-01

The release of cadmium into many coastal areas represents a threat to ecosystems and human health; cadmium is carcinogenic in mammals and in both marine invertebrates and vertebrates. The use of molluscs to assess the ecologic risk associated with contaminants is strongly recommended on account of their ecological role and on their highly conserved control and regulatory pathways that are often homologous to vertebrate systems. We previously identified a midkine family protein in the limpet Patella caerulea; the midkine is a recently discovered cytokines family with unequivocal informative value on repairing injury and neoplastic processes in mammals. Here we report on midkine ( mdk) and α-tubulin ( α-tub) gene expression patterns in P. caerulea exposed to cadmium. Limpets, collected on two occasions from a breakwater at a marina (Tyrrhenian Sea) were exposed to sublethal cadmium concentrations (0.5 and 1 mg l -1 Cd) over a 10-day exposure period. RNA was extracted from the viscera of unexposed and exposed specimens. Real time TaqMan RT-PCR was performed to measure the relative mdk and α-tub gene expression levels. A remarkable mdk over-expression was observed in all exposed animals with respect to unexposed ones; mdk over-expression was significantly higher in both treatments when compared with un-treatment (mean expression levels: 23- and 38-fold, for 0.5 and 1 mg l -1 Cd treatment, respectively; ANOVA, for both P < 0.01). The study also indicates that the mdk up-regulation was significantly Cd-concentration dependent ( P < 0.05). A significant up-regulation of the constitutive α-tub gene was also observed in 1 mg l -1 Cd-treated animals (mean expression level: 4-fold; ANOVA, P < 0.05). In conclusion, these data provide the first evidence paving the way for the use of the midkine as a promising new biomarker of effect in the environment risk assessment policy.

Context- and Cell-Dependent Effects of Delta-Like 4 Targeting in the Bone Marrow Microenvironment

PubMed Central

Remédio, Leonor; Carvalho, Tânia; Caiado, Francisco; Bastos-Carvalho, Ana; Martins, Diana; Duarte, António; Yagita, Hideo; Dias, Sergio

2012-01-01

Delta-like 4 (Dll4) is a ligand of the Notch pathway family which has been widely studied in the context of tumor angiogenesis, its blockade shown to result in non-productive angiogenesis and halted tumor growth. As Dll4 inhibitors enter the clinic, there is an emerging need to understand their side effects, namely the systemic consequences of Dll4:Notch blockade in tissues other than tumors. The present study focused on the effects of systemic anti-Dll4 targeting in the bone marrow (BM) microenvironment. Here we show that Dll4 blockade with monoclonal antibodies perturbs the BM vascular niche of sub-lethally irradiated mice, resulting in increased CD31+, VE-Cadherin+ and c-kit+ vessel density, and also increased megakaryocytes, whereas CD105+, VEGFR3+, SMA+ and lectin+ vessel density remained unaltered. We investigated also the expression of angiocrine genes upon Dll4 treatment in vivo, and demonstrate that IGFbp2, IGFbp3, Angpt2, Dll4, DHH and VEGF-A are upregulated, while FGF1 and CSF2 are reduced. In vitro treatment of endothelial cells with anti-Dll4 reduced Akt phosphorylation while maintaining similar levels of Erk 1/2 phosphorylation. Besides its effects in the BM vascular niche, anti-Dll4 treatment perturbed hematopoiesis, as evidenced by increased myeloid (CD11b+), decreased B (B220+) and T (CD3+) lymphoid BM content of treated mice, with a corresponding increase in myeloid circulating cells. Moreover, anti-Dll4 treatment also increased the number of CFU-M and -G colonies in methylcellulose assays, independently of Notch1. Finally, anti-Dll4 treatment of donor BM improved the hematopoietic recovery of lethally irradiated recipients in a transplant setting. Together, our data reveals the hematopoietic (BM) effects of systemic anti-Dll4 treatment result from qualitative vascular changes and also direct hematopoietic cell modulation, which may be favorable in a transplant setting. PMID:23285048

iTRAQ-based proteomic analysis reveals the mechanisms of silicon-mediated cadmium tolerance in rice (Oryza sativa) cells.

PubMed

Ma, Jie; Sheng, Huachun; Li, Xiuli; Wang, Lijun

2016-07-01

Silicon (Si) can alleviate cadmium (Cd) stress in rice (Oryza sativa) plants, however, the understanding of the molecular mechanisms at the single-cell level remains limited. To address these questions, we investigated suspension cells of rice cultured in the dark environment in the absence and presence of Si with either short- (12 h) or long-term (5 d) Cd treatments using a combination of isobaric tags for relative and absolute quantitation (iTRAQ), fluorescent staining, and inductively coupled plasma mass spectroscopy (ICP-MS). We identified 100 proteins differentially regulated by Si under the short- or long-term Cd stress. 70% of these proteins were down-regulated, suggesting that Si may improve protein use efficiency by maintaining cells in the normal physiological status. Furthermore, we showed two different mechanisms for Si-mediated Cd tolerance. Under the short-term Cd stress, the Si-modified cell walls inhibited the uptake of Cd ions into cells and consequently reduced the expressions of glycosidase, cell surface non-specific lipid-transfer proteins (nsLTPs), and several stress-related proteins. Under the long-term Cd stress, the amount of Cd in the cytoplasm in Si-accumulating (+Si) cells was decreased by compartmentation of Cd into vacuoles, thus leading to a lower expression of glutathione S-transferases (GST). These results provide protein-level insights into the Si-mediated Cd detoxification in rice single cells. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Lethal and sub-lethal responses of native freshwater mussels exposed to granular Bayluscide®, a sea lamprey larvicide

USGS Publications Warehouse

Newton, Teresa; Boogaard, Michael A.; Gray, Brian R.; Hubert, Terrance D.; Schloesser, Nicholas

2017-01-01

The invasive sea lamprey (Petromyzon marinus) poses a substantial threat to fish communities in the Great Lakes. Efforts to control sea lamprey populations typically involve treating tributary streams with lampricides on a recurring cycle. The presence of a substantial population of larval sea lampreys in the aquatic corridor between Lakes Huron and Erie prompted managers to propose a treatment using the granular formulation of Bayluscide® that targets larval sea lampreys that reside in sediments. However, these treatments could cause adverse effects on native freshwater mussels—imperiled animals that also reside in sediments. We estimated the risk of mortality and sub-lethal effects among eight species of adult and sub-adult mussels exposed to Bayluscide® for durations up to 8 h to mimic field applications. Mortality was appreciable in some species, especially in sub-adults (range, 23–51%). The lethal and sub-lethal effects were positively associated with the duration of exposure in most species and life stage combinations. Estimates of the median time of exposure that resulted in lethal and sub-lethal effects suggest that sub-adults were often affected by Bayluscide® earlier than adults. Siphoning activity and burrowing position of mussels during exposure may have moderated the uptake of Bayluscide® and may have influenced lethal and sub-lethal responses. Given that the various species and life stages were differentially affected, it will be difficult to predict the effects of Bayluscide® treatments on mussels.

[Ex vivo expansion and clonal variation of CD34(+)CD59(+) cells from bone marrow in children with paroxysmal nocturnal hemoglobinuria].

PubMed

Xiao, Juan; Wu, Yong-Ji; Han, Bing; Dong, Hong-Yan; Chen, Shi-Ping

2013-08-01

To investigate the isolation, purification and ex vivo expansion of CD34(+)CD59(+) cells from the bone marrow of children with paroxysmal nocturnal hemoglobinuria (PNH), to evaluate the capability of long-term hematopoietic reconstruction of the expanded CD34(+)CD59(+) cells, and to provide a laboratory basis for novel treatment of PNH. CD34(+)CD59(+) cells were isolated from the bone marrow mononuclear cells of children with PNH using immunomagnetic beads and flow cytometer in sequence. The isolated cells were subjected to ex vivo expansion in the presence of different combinations of hematopoietic growth factors for two weeks. The colony-forming cells and long-term culture-initiating cells (LTC-ICs) were cultured and counted. The optimal combination of hematopoietic growth factors for ex vivo expansion was stem cell factor+interleukin (IL)-3+IL-6+FLT3 ligand+thrombopoietin+ery-thropoietin, and maximum expansion (30.4 ± 6.7 folds) was seen on day 7 of days 4 to 14 of ex vivo expansion. After ex vivo expansion, CD34(+)CD59(+) cells remained CD59-positive, retained strong capability of forming colony-forming units, and could still form LTC-ICs. There was no significant difference in capability of forming LTC-ICs between CD34(+)CD59(+) cells before and after expansion. The expansion capability of CD34(+)CD59(+) cells from children with PNH was significantly lower than that of CD34(+) cells from normal controls (P<0.01). The CD34(+)CD59(+) cells from children with PNH can be expanded in vitro. Post-expansion CD34(+)CD59(+) cells retain capability of long-term hematopoietic reconstruction. CD34(+)CD59(+) cells showed no trend towards PNH clone during culture. Ex vivo expansion of CD34(+)CD59(+) cells from children with PNH might be practical in performing autologous transplantation clinically for these children.

Effects of turbidity, sediment, and polyacrylamide on native freshwater mussels

USGS Publications Warehouse

Buczek, Sean B.; Cope, W. Gregory; McLaughlin, Richard A.; Kwak, Thomas J.

2018-01-01

Turbidity is a ubiquitous pollutant adversely affecting water quality and aquatic life in waterways globally. Anionic polyacrylamide (PAM) is widely used as an effective chemical flocculent to reduce suspended sediment (SS) and turbidity. However, no information exists on the toxicity of PAM‐flocculated sediments to imperiled, but ecologically important, freshwater mussels (Unionidae). Thus, we conducted acute (96 h) and chronic (24 day) laboratory tests with juvenile fatmucket (Lampsilis siliquoidea) and three exposure conditions (nonflocculated settled sediment, SS, and PAM‐flocculated settled sediment) over a range of turbidity levels (50, 250, 1,250, and 3,500 nephelometric turbidity units). Survival and sublethal endpoints of protein oxidation, adenosine triphosphate (ATP) production, and protein concentration were used as measures of toxicity. We found no effect of turbidity levels or exposure condition on mussel survival in acute or chronic tests. However, we found significant reductions in protein concentration, ATP production, and oxidized proteins in mussels acutely exposed to the SS condition, which required water movement to maintain sediment in suspension, indicating responses that are symptoms of physiological stress. Our results suggest anionic PAM applied to reduce SS may minimize adverse effects of short‐term turbidity exposure on juvenile freshwater mussels without eliciting additional lethal or sublethal toxicity.

Assessment of Sublethal and Transgenerational Effects of Pirimicarb on the Wheat Aphids Rhopalosiphum padi and Sitobion avenae

PubMed Central

Desneux, Nicolas; Han, Peng; Gao, Xiwu

2015-01-01

The wheat aphids, Rhopalosiphum padi (Linnaeus) and Sitobion avenae (Fabricius), are key pests on wheat crops worldwide. Management practices rely primarily on insecticides. The pirimicarb (carbamate) is used extensively as an effective insecticide to control these two aphids. In addition to the mortality caused by pirimicarb, various sublethal effects may occur in aphids when exposed to low lethal or sublethal doses. Understanding the general effect of pirimicarb on aphids could help increasing rational use of this insecticide. Under laboratory conditions, we assessed the sublethal effects of a low lethal concentration of pirimicarb (LC25) on biological traits and acetylcholinesterase (AChE) activity of R. padi and S. avenae. Both direct and transgenerational effects, i.e. on parent and the F1 generations were assessed, respectively. We found that R. padi and S. avenae responded differentially to the LC25 of pirimicarb. The parent generation of R. padi showed a 39% decrease in fecundity and multiple transgenerational effects were observed in the F1 generation; overall juvenile development, reproductive period, adult longevity and lifespan were longer than those of the control group. By contrast, LC25 of pirimicarb showed almost no effects on S. avenae biological traits in both the parent and F1 generations; only the pre-reproductive duration was reduced in F1 generations. Demographic parameter estimates (e.g. rm) showed similar trend, i.e. significant negative effect on R. padi population growth and no effect on S. avenae. However, AChE activity decreased in both R. padi and S. avenae treated by the LC25 of pirimicarb. We demonstrated sublethal and transgenerational effects of pirimicarb in the two wheat aphid species; it hinted at the importance of considering sublethal effects (including hormesis) of pirimicarb for optimizing Integrated Pest Management (IPM) of wheat aphids. PMID:26121265

Is the risk for soil arthropods covered by new data requirements under the EU PPP Regulation No. 1107/2009?

PubMed

Kohlschmid, E; Ruf, D

2016-12-01

Testing of effects on earthworms and non-target foliar arthropods is an integral part of the ecotoxicological risk assessment for the authorization of plant protection products. According to the new data requirements, which came into force in 2014 for active substances and in 2016 for plant protection products, the chronic earthworm toxicity test with Eisenia fetida based on reproductive, growth, and behavioral effects instead of the acute earthworm toxicity test based on mortality, has to be conducted routinely. Additional testing of effects on soil arthropods (Folsomia candida, Hyposaspis aculeifer) is required if the risk assessment of foliar applications raises concerns regarding non-target foliar arthropods (Aphidius rhopalosiphi, Typhlodromus pyri) or if the product is applied directly on or into the soil. Thus, it was investigated whether the sublethal earthworm endpoint is more sensitive than the sublethal soil arthropod endpoint for different types of pesticides and whether the risk assessment for non-target arthropods would trigger the testing of effects on soil arthropods in the cases where soil arthropods are more sensitive than earthworms. Toxicity data were obtained from Swiss ecotoxicological database, EFSA Conclusions and scientific literature. For insecticides and herbicides, no general conclusion regarding differences in sensitivity of either earthworms or soil arthropods based on sublethal endpoints were possible. For fungicides, the data indicated that in general, earthworms seemed to be more sensitive than soil arthropods. In total, the sublethal F. candida or H. aculeifer endpoint was lower than the sublethal E. fetida endpoint for 23 (34 %) out of 68 active substances. For 26 % of these 23 active substances, testing of soil arthropods would not have been triggered due to the new data requirement. These results based on sublethal endpoints show that earthworms and soil arthropods differ in sensitivity toward certain active substances and that the risk assessment for non-target foliar arthropods did not always trigger soil arthropod testing in the cases where soil arthropods were more sensitive than earthworms.

Long-term efficiency of mesenchymal stromal cell-mediated CD-MSC/5FC therapy in human melanoma xenograft model.

PubMed

Kucerova, L; Skolekova, S; Demkova, L; Bohovic, R; Matuskova, M

2014-10-01

Mesenchymal stromal cells (MSC) can be exploited as cellular delivery vehicles for the enzymes converting non-toxic prodrugs to toxic substances. Because of their inherent chemoresistance, they exert potent bystander and antitumor effect. Here we show that the human adipose tissue-derived MSC expressing fusion yeast cytosine deaminase::uracil phosphoribosyltransferase (CD-MSC) in combination with 5-fluorocytosine (5FC) mediated a long-term tumor-free survival in the 83.3% of tumor-bearing animals. CD-MSC/5FC treatment induced cytotoxicity against model human melanoma cells EGFP-A375. Only 4% of the therapeutic CD-MSC cells eliminated >98.5% of the tumor cells in vitro. Long-term tumor-free survival was confirmed in 15 out of the 18 animals. However, repeatedly used CD-MSC/5FC therapeutic regimen generated more aggressive and metastatic variant of the melanoma cells EGFP-A375/Rel3. These cells derived from the refractory xenotransplants exhibited increased resistance to the CD-MSC/5FC treatment, altered cell adhesion, migration, tumorigenic and metastatic properties. However, long-term curative effect was achieved by the augmentation of the CD-MSC/5FC regimen along with the inhibition of c-Met/hepatocyte growth factor signaling axis in this aggressive melanoma derivative. In summary, the CD-MSC/5FC regimen can be regarded as a very effective antitumor approach to achieve long-term tumor-free survival as demonstrated on a mouse model of aggressive human melanoma xenografts.

T-Cell-Mediated Immune Responses in Patients with Cutaneous or Mucosal Leishmaniasis: Long-Term Evaluation after Therapy

PubMed Central

Da-Cruz, Alda Maria; Bittar, Rita; Mattos, Marise; Oliveira-Neto, Manuel P.; Nogueira, Ricardo; Pinho-Ribeiro, Vanessa; Azeredo-Coutinho, Rilza Beatriz; Coutinho, Sergio G.

2002-01-01

T-cell immune responses in patients with cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) were studied during the active disease, at the end of therapy, and 1 to 17 years posttherapy (long-term follow-up). Lymphocyte proliferative responses, phenotypic characterization of CD4+ and CD8+ Leishmania-reactive T cells, and cytokine production were assayed. Patients with active ML and CL showed higher proportions of CD4+ than CD8+ T cells. In CL, the healing process was associated with a decrease of CD4+ and an increase of CD8+, leading to similar CD4+ and CD8+ proportions. This pattern was only seen in ML after long-term therapy. Long-term follow-up of patients with CL showed a positive CD4+/CD8+ ratio as observed during the active disease, although the percentages of these T cell subsets were significantly lower. Patients with CL did not show significant differences between gamma interferon (IFN-γ) and interleukin-5 (IL-5) production during the period of study. Patients with active ML presented higher IFN-γ and IL-5 levels compared to patients with active CL. IL-4 was only detected during active disease. Patients long term after cure from ML showed increasing production of IFN-γ, significant decrease of IL-5, and no IL-4 production. Two apparently beneficial immunological parameters were detected in tegumentary leishmaniasis: (i) decreasing proportions of CD4+ Leishmania-reactive T cells in the absence of IL-4 production associated with cure of CL and ML and (ii) decreasing levels of IL-5 long after cure, better detected in patients with ML. The observed T-cell responses maintained for a long period in healed patients could be relevant for immunoprotection against reinfection and used as a parameter for determining the prognosis of patients and selecting future vaccine preparations. PMID:11874860

Monitoring of metal pollution in waterways across Bangladesh and ecological and public health implications of pollution.

PubMed

Kibria, Golam; Hossain, Md Maruf; Mallick, Debbrota; Lau, T C; Wu, Rudolf

2016-12-01

Using innovative artificial mussels technology for the first time, this study detected eight heavy metals (Cd, Cu, Fe, Mn, Ni, Pb, U, Zn) on a regular basis in waterways across Bangladesh (Chittagong, Dhaka and Khulna). Three heavy metals, viz. Co, Cr and Hg were always below the instrumental detection levels in all the sites during the study period. Through this study, seven metal pollution "hot spots" have been identified, of which, five "hot spots" (Cu, Fe, Mn, Ni, Pb) were located in the Buriganga River, close to the capital Dhaka. Based on this study, the Buriganga River can be classified as the most polluted waterway in Bangladesh compared to waterways monitored in Khulna and Chittagong. Direct effluents discharged from tanneries, textiles are, most likely, reasons for elevated concentrations of heavy metals in the Buriganga River. In other areas (Khulna), agriculture and fish farming effluents may have caused higher Cu, U and Zn in the Bhairab and Rupsa Rivers, whereas untreated industrial discharge and ship breaking activities can be linked to elevated Cd in the coastal sites (Chittagong). Metal pollution may cause significant impacts on water quality (irrigation, drinking), aquatic biodiversity (lethal and sub-lethal effects), food contamination/food security (bioaccumulation of metals in crops and seafood), human health (diseases) and livelihoods of people associated with wetlands. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Effect of different oxygen concentrations on biological properties of bone marrow hematopoietic stem cells of mice].

PubMed

Ma, Yi-Ran; Ren, Si-Hua; He, Yu-Xin; Wang, Lin-Lin; Jin, Li; Hao, Yi-Wen

2012-10-01

This study purposed to investigate the effects of different oxygen concentrations and reactive oxygen species (ROS) on the biological characteristics of hematopoietic stem cells (HSC) and their possible mechanisms through simulating oxygen environment to which the peripheral blood HSC are subjected in peripheral blood HSCT. The proliferation ability, cell cycle, directed differentiation ability, ROS level and hematopoietic reconstitution ability of Lin(-)c-kit(+)Sca-1(+) BMHSC were detected by using in vitro amplification test, directional differentiation test, cell cycle analysis, ROS assay and transplantation of Lin(-)c-kit(+)Sca-1(+) HSC from sublethally irradiated mice respectively. The results showed that oxygen concentrations lower than normal oxygen concentration, especially in hypoxic oxygen environment, could reduce ROS generation and amplify more primitive CD34(+)AC133(+) HSC and active CD34(+) HSC, and maintain more stem cells in the G(0)/G(1) phase, which is more helpful to the growth of CFU-S and viability of mice. At the same time, BMHSC exposed to normal oxygen level or inconstant and greatly changed oxygen concentrations could produce a high level of ROS, and the above-mentioned features and functional indicators are relatively low. It is concluded that ROS levels of HSC in BMHSCT are closely related with the oxygen concentration surrounding the cells and its stability. Low oxygen concentration and antioxidant intervention are helpful to transplantation of BMHSC.

Developing acute-to-chronic toxicity ratios for lead, cadmium, and zinc using rainbow trout, a mayfly, and a midge

USGS Publications Warehouse

Mebane, C.A.; Hennessy, D.P.; Dillon, F.S.

2008-01-01

In order to estimate acute-to-chronic toxicity ratios (ACRs) relevant to a coldwater stream community, we exposed rainbow trout (Oncorhynchus mykiss) to cadmium (Cd), lead (Pb), and zinc (Zn) in 96-h acute and 60+ day early-life stage (ELS) exposures. We also tested the acute and sublethal responses of a mayfly (Baetis tricaudatus) and a midge (Chironomus dilutus, formerly C. tentans) with Pb. We examine the statistical interpretation of test endpoints and the acute-to-chronic ratio concept. Increasing the number of control replicates by 2 to 3x decreased the minimum detectable differences by almost half. Pb ACR estimates mostly increased with increasing acute resistance of the organisms (rainbow trout ACRs

Improving Gene Therapy Efficiency through the Enrichment of Human Hematopoietic Stem Cells.

PubMed

Masiuk, Katelyn E; Brown, Devin; Laborada, Jennifer; Hollis, Roger P; Urbinati, Fabrizia; Kohn, Donald B

2017-09-06

Lentiviral vector (LV)-based hematopoietic stem cell (HSC) gene therapy is becoming a promising clinical strategy for the treatment of genetic blood diseases. However, the current approach of modifying 1 × 10 8 to 1 × 10 9 CD34 + cells per patient requires large amounts of LV, which is expensive and technically challenging to produce at clinical scale. Modification of bulk CD34 + cells uses LV inefficiently, because the majority of CD34 + cells are short-term progenitors with a limited post-transplant lifespan. Here, we utilized a clinically relevant, immunomagnetic bead (IB)-based method to purify CD34 + CD38 - cells from human bone marrow (BM) and mobilized peripheral blood (mPB). IB purification of CD34 + CD38 - cells enriched severe combined immune deficiency (SCID) repopulating cell (SRC) frequency an additional 12-fold beyond standard CD34 + purification and did not affect gene marking of long-term HSCs. Transplant of purified CD34 + CD38 - cells led to delayed myeloid reconstitution, which could be rescued by the addition of non-transduced CD38 + cells. Importantly, LV modification and transplantation of IB-purified CD34 + CD38 - cells/non-modified CD38 + cells into immune-deficient mice achieved long-term gene-marked engraftment comparable with modification of bulk CD34 + cells, while utilizing ∼7-fold less LV. Thus, we demonstrate a translatable method to improve the clinical and commercial viability of gene therapy for genetic blood cell diseases. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Oxidative stress, endocrine disruption, and malformation of Bufo gargarizans embryo exposed to sub-lethal cadmium concentrations.

PubMed

Wu, Chao; Zhang, Yuhui; Chai, Lihong; Wang, Hongyuan

2017-01-01

Thyroid hormone (TH) is critical for vertebrate postembryonic development as well as embryonic development. Chinese toad (Bufo gargarizans) embryos were exposed to different concentrations of cadmium (5, 50, 100, 200 and 500μg Cd L -1 ) for 7days. Malformations were monitored daily, and growth and development of embryos were measured at day 4 and 7, and type 2 and 3 iodothyronine deiodinase (Dio2 and Dio3), thyroid hormone receptors (TRα and TRβ) mRNA levels were also measured to assess disruption of TH synthesis. In addition, superoxide dismutase (SOD), glutathione peroxidase (GPx) and heat shock proteins (HSPs) mRNA expression were examined to evaluate the ability of scavenging ROS. Our results demonstrated a bimodal inhibitory effect of Cd on the embryo growth and development of Bufo gargarizans. Reduced mean stage, total length and weight were observed at 5, 50, 200 and 500, but not at 100μg Cd L -1 . Embryos malformation occurred in all cadmium treatments. Morphological abnormalities of embryos are characterized by axial flexures, abdominal edema, stunted growth and fin flexure. Real-time PCR results show that exposure to cadmium down-regulated TRα and Dio3 mRNA expression and up-regulated Dio2 mRNA level. SOD and GPx mRNA expression was significantly up-regulated after cadmium exposure. We concluded that cadmium could change mRNA expression of TRα, Dio2 and Dio3 leading the inhibition of growth and development of B. gargarizans embryo, which suggests that cadmium might have the endocrine-disrupting effect in embryos. Moreover, the reduced ability of scavenging ROS induced by cadmium might be responsible for the teratogenic effects of cadmium. Copyright © 2016 Elsevier B.V. All rights reserved.

Blockade of p38 Mitogen-Activated Protein Kinase Inhibits Murine Sclerodermatous Chronic Graft-versus-Host Disease.

PubMed

Matsushita, Takashi; Date, Mutsumi; Kano, Miyu; Mizumaki, Kie; Tennichi, Momoko; Kobayashi, Tadahiro; Hamaguchi, Yasuhito; Hasegawa, Minoru; Fujimoto, Manabu; Takehara, Kazuhiko

2017-04-01

Bone marrow transplantation (BMT) of B10.D2 mice into sublethally irradiated BALB/c mice across minor histocompatibility loci is a well-established animal model for human sclerodermatous chronic graft-versus-host disease (Scl-cGVHD) and systemic sclerosis (SSc). The p38 mitogen-activated protein kinase (MAPK) pathway is a key regulator of inflammation and cytokine production. Furthermore, the activation of p38 MAPK plays an important role in collagen production in SSc. We investigated the effects of p38 MAPK inhibitor, VX-702, on Scl-cGVHD mice. VX-702 was orally administered to Scl-cGVHD mice from day 7 to 35 after BMT. We compared skin fibrosis of Scl-cGVHD mice between the VX-702-treated group and control group. Allogeneic BMT increased the phosphorylation of p38 MAPK in the skin. The administration of VX-702 attenuated the skin fibrosis of Scl-cGVHD compared to the control mice. Immunohistochemical staining showed that VX-702 suppressed the infiltration of CD4 + T cells, CD8 + T cells, and CD11b + cells into the dermis of Scl-cGVHD mice compared to the control mice. VX-702 attenuated the mRNA expression of extracellular matrix and fibrogenic cytokines, such as IL-6 and IL-13, in the skin of Scl-cGVHD mice. In addition, VX-702 directly inhibited collagen production from fibroblasts in vitro. VX-702 was shown to be a promising candidate for use in treating patients with Scl-cGVHD and SSc. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Effects of heavy metals on Cyanothece sp. CCY 0110 growth, extracellular polymeric substances (EPS) production, ultrastructure and protein profiles.

PubMed

Mota, Rita; Pereira, Sara B; Meazzini, Marianna; Fernandes, Rui; Santos, Arlete; Evans, Caroline A; De Philippis, Roberto; Wright, Phillip C; Tamagnini, Paula

2015-04-29

The effects of several heavy metals on the growth/survival, EPS production, ultrastructure and protein profiles of the highly efficient extracellular polymeric substances (EPS)-producer cyanobacterium Cyanothece sp. CCY 0110 were evaluated. Our results clearly show that each heavy metal affects the cells in a particular manner, triggering distinctive responses. Concerning chronic exposure, cells were more affected by Cu(2+) followed by Pb(2+), Cd(2+), and Li(+). The presence of metal leads to remarkable ultrastructural changes, mainly at the thylakoid level. The comparison of the proteomes (iTRAQ) allowed to follow the stress responses and to distinguish specific effects related to the time of exposure and/or the concentration of an essential (Cu(2+)) and a non-essential (Cd(2+)) metal. The majority of the proteins identified and with fold changes were associated with photosynthesis, CO2 fixation and carbohydrate metabolism, translation, and nitrogen and amino acid metabolism. Moreover, our results indicate that during chronic exposure to sub-lethal concentrations of Cu(2+), the cells tune down their metabolic rate to invest energy in the activation of detoxification mechanisms, which eventually result in a remarkable recovery. In contrast, the toxic effects of Cd(2+) are cumulative. Unexpectedly, the amount of released polysaccharides (RPS) was not enhanced by the presence of heavy metals. This work shows the holistic effects of different heavy metals on the cells of the highly efficient EPS-producer the cyanobacterium Cyanothece sp. CCY 0110. The growth/survival, EPS production, ultrastructure, protein profiles and stress response were evaluated. The knowledge generated by this study will contribute to the implementation of heavy-metal removal systems based on cyanobacteria EPS or their isolated polymers. Copyright © 2015. Published by Elsevier B.V.

Establishment of a novel endothelial target mouse model of a typhus group rickettsiosis: evidence for critical roles for gamma interferon and CD8 T lymphocytes.

PubMed

Walker, D H; Popov, V L; Feng, H M

2000-09-01

A mouse model of typhus rickettsiosis that reproduces the hematogenous dissemination to the critical target organs, including brain, lungs, heart, and kidneys, primary endothelial and, to a lesser degree, macrophage intracellular rickettsial infection, and typical vascular-based lesions of louse-borne typhus and murine typhus was established. Intravenous inoculation of C3H/HeN mice with Rickettsia typhi caused disease with a duration of the incubation period and mortality rate that were dependent on the infective dose of rickettsiae. Lethal infection was associated with high concentrations of R. typhi in the lungs and brain, despite a brisker humoral immune response to the rickettsiae than in the sublethal infection. Gamma interferon and CD8 T lymphocytes were demonstrated to be crucial to clearance of the rickettsiae and recovery from infection in experiments in which specific monoclonal antibodies were administered to deplete these components. Death of animals depleted of gamma interferon or CD8 T lymphocytes was associated with overwhelming rickettsial infection demonstrated by titers of infectious rickettsiae and by immunohistochemistry. An effective antirickettsial immune response was associated with elevated serum concentrations of IL-12 on Day 5 and increased secretion of IL-12 by concanavalin-A-stimulated spleen cells on Day 5. Evidence for transient suppression of the immune response consisted of marked reduction in the secretion of IL-2 and IL-12 by concanavalin-A-stimulated spleen cells on Days 10 and 15. This model offers excellent opportunities for study of attenuation and pathogenetic mechanisms of typhus rickettsiae, which are established biologic weapons of potential use in bioterrorism.

[Monitoring early toxicity of heavy metals including Hg using a HSE-SEAP reporter gene].

PubMed

Yu, Zhan-Jiang; Yang, Qin; Yang, Xiao-Da; Wang, Kui

2006-08-01

To develop a cellular assay based on heat shock signal pathway and secreted alkaline phosphatase (SEAP) reporter gene for investigating/predicting the early toxicity of heavy metals on HeLa cells in Chinese traditional medicine (TCM). The pHSE-SEAP plasmid was transfected into HeLa cells to build a HSE-SEAP-HeLa cell model. For validation of the model, the transfected cells were treated by either heating at 42 degrees C for 1 h or incubated with 5 mol x L(-1) CdCl2 for 4 h. Then the cells were covered in complete DMEM culture medium for 48 h and the activity of SEAP (reflecting the cellular level of heat shock protein) in cultural supernatants was measured; meanwhile, cell viability was determined by MTT assays. In addition, the cells were treated by four mercury compounds, HgCl2, merthilate sodium, HgS and cinnabar at the sub-lethal concentrations (determined by MTT assays). Then the heat shock response was detected likewise. Significant level of secreted alkaline phosphatase (SEAP) was found in pHSE-SEAP transfected HeLa cells treated either by heating (42 degrees C) or incubating with CdCl2. The heat shock protein was induced by CdCl2 before decrease of cell viability was observed. All four mercury compounds induced heat shock response in both time and concentration-dependant manner. However, there were big differences among the mercury compounds, suggesting potential differences for early-stage toxicity in vivo. The pHSE-SEAP transfected HeLa cells respond effectively to heat shock and metal stresses, and therefore provide a practical and repeatable assay for investigating/predicting the early toxicity of heavy metals and mineral-containing drugs in TCM.

RIG-I-like helicases induce immunogenic cell death of pancreatic cancer cells and sensitize tumors toward killing by CD8+ T cells

PubMed Central

Duewell, P; Steger, A; Lohr, H; Bourhis, H; Hoelz, H; Kirchleitner, S V; Stieg, M R; Grassmann, S; Kobold, S; Siveke, J T; Endres, S; Schnurr, M

2014-01-01

Pancreatic cancer is characterized by a microenvironment suppressing immune responses. RIG-I-like helicases (RLH) are immunoreceptors for viral RNA that induce an antiviral response program via the production of type I interferons (IFN) and apoptosis in susceptible cells. We recently identified RLH as therapeutic targets of pancreatic cancer for counteracting immunosuppressive mechanisms and apoptosis induction. Here, we investigated immunogenic consequences of RLH-induced tumor cell death. Treatment of murine pancreatic cancer cell lines with RLH ligands induced production of type I IFN and proinflammatory cytokines. In addition, tumor cells died via intrinsic apoptosis and displayed features of immunogenic cell death, such as release of HMGB1 and translocation of calreticulin to the outer cell membrane. RLH-activated tumor cells led to activation of dendritic cells (DCs), which was mediated by tumor-derived type I IFN, whereas TLR, RAGE or inflammasome signaling was dispensable. Importantly, CD8α+ DCs effectively engulfed apoptotic tumor material and cross-presented tumor-associated antigen to naive CD8+ T cells. In comparison, tumor cell death mediated by oxaliplatin, staurosporine or mechanical disruption failed to induce DC activation and antigen presentation. Tumor cells treated with sublethal doses of RLH ligands upregulated Fas and MHC-I expression and were effectively sensitized towards Fas-mediated apoptosis and cytotoxic T lymphocyte (CTL)-mediated lysis. Vaccination of mice with RLH-activated tumor cells induced protective antitumor immunity in vivo. In addition, MDA5-based immunotherapy led to effective tumor control of established pancreatic tumors. In summary, RLH ligands induce a highly immunogenic form of tumor cell death linking innate and adaptive immunity. PMID:25012502

A COMPARISON OF THE LETHAL AND SUBLETHAL TOXICITY OF ORGANIC CHEMICAL MIXTURES TO THE FATHEAD MINNOW (PIMEPHALES PROMELAS)

EPA Science Inventory

The joint toxic effects of known binary and multiple organic chemical mixtures to the fathead minnow (Pimephales promelas) were defined at both the 96-h 50% lethal effect concentration (LC50) and sublethal (32-d growth) response levels for toxicants with a narcosis I, narcosis II...

Sublethal effects of cadmium on physiological responses in the pocketbook mussel, Lampsilis ventricosa

USGS Publications Warehouse

Naimo, T.J.; Atchison, G.J.; Holland Bartels, L. E.

1992-01-01

Several physiological responses have been used to evaluate the effects of contaminants on marine bivalves. Respiration rate, food clearance rate, ammonia excretion rate, and food assimilation efficiency can be quantified and incorporated into a bioenergetics model known as scope for growth. This model estimates an organism's instantaneous energy budget and quantifies the available energy for growth and reproduction. We applied some of these physiological techniques to freshwater mussels to determine the sublethal effects of cadmium. The objective of our study was to quantify the physiological responses of adult pocketbook mussels, Lampsilis ventricosa , exposed to sublethal concentrations of cadmium. We selected L. ventricosa for study because it is abundant in the upper Mississippi River and its life history has been partially documented.

Dynamic Interaction- and Phospho-Proteomics Reveal Lck as a Major Signaling Hub of CD147 in T Cells.

PubMed

Supper, Verena; Hartl, Ingrid; Boulègue, Cyril; Ohradanova-Repic, Anna; Stockinger, Hannes

2017-03-15

Numerous publications have addressed CD147 as a tumor marker and regulator of cytoskeleton, cell growth, stress response, or immune cell function; however, the molecular functionality of CD147 remains incompletely understood. Using affinity purification, mass spectrometry, and phosphopeptide enrichment of isotope-labeled peptides, we examined the dynamic of the CD147 microenvironment and the CD147-dependent phosphoproteome in the Jurkat T cell line upon treatment with T cell stimulating agents. We identified novel dynamic interaction partners of CD147 such as CD45, CD47, GNAI2, Lck, RAP1B, and VAT1 and, furthermore, found 76 CD147-dependent phosphorylation sites on 57 proteins. Using the STRING protein network database, a network between the CD147 microenvironment and the CD147-dependent phosphoproteins was generated and led to the identification of key signaling hubs around the G proteins RAP1B and GNB1, the kinases PKCβ, PAK2, Lck, and CDK1, and the chaperone HSPA5. Gene ontology biological process term analysis revealed that wound healing-, cytoskeleton-, immune system-, stress response-, phosphorylation- and protein modification-, defense response to virus-, and TNF production-associated terms are enriched within the microenvironment and the phosphoproteins of CD147. With the generated signaling network and gene ontology biological process term grouping, we identify potential signaling routes of CD147 affecting T cell growth and function. Copyright © 2017 by The American Association of Immunologists, Inc.

CD133-targeted gene transfer into long-term repopulating hematopoietic stem cells.

PubMed

Brendel, Christian; Goebel, Benjamin; Daniela, Abriss; Brugman, Martijn; Kneissl, Sabrina; Schwäble, Joachim; Kaufmann, Kerstin B; Müller-Kuller, Uta; Kunkel, Hana; Chen-Wichmann, Linping; Abel, Tobias; Serve, Hubert; Bystrykh, Leonid; Buchholz, Christian J; Grez, Manuel

2015-01-01

Gene therapy for hematological disorders relies on the genetic modification of CD34(+) cells, a heterogeneous cell population containing about 0.01% long-term repopulating cells. Here, we show that the lentiviral vector CD133-LV, which uses a surface marker on human primitive hematopoietic stem cells (HSCs) as entry receptor, transfers genes preferentially into cells with high engraftment capability. Transduction of unstimulated CD34(+) cells with CD133-LV resulted in gene marking of cells with competitive proliferative advantage in vitro and in immunodeficient mice. The CD133-LV-transduced population contained significantly more cells with repopulating capacity than cells transduced with vesicular stomatitis virus (VSV)-LV, a lentiviral vector pseudotyped with the vesicular stomatitis virus G protein. Upon transfer of a barcode library, CD133-LV-transduced cells sustained gene marking in vivo for a prolonged period of time with a 6.7-fold higher recovery of barcodes compared to transduced control cells. Moreover, CD133-LV-transduced cells were capable of repopulating secondary recipients. Lastly, we show that this targeting strategy can be used for transfer of a therapeutic gene into CD34(+) cells obtained from patients suffering of X-linked chronic granulomatous disease. In conclusion, direct gene transfer into CD133(+) cells allows for sustained long-term engraftment of gene corrected cells.

Mesenchymal stem cells from the Wharton's jelly of umbilical cord segments provide stromal support for the maintenance of cord blood hematopoietic stem cells during long-term ex vivo culture.

PubMed

Bakhshi, Tiki; Zabriskie, Ryan C; Bodie, Shamanique; Kidd, Shannon; Ramin, Susan; Paganessi, Laura A; Gregory, Stephanie A; Fung, Henry C; Christopherson, Kent W

2008-12-01

Hematopoietic stem cells (HSCs) are routinely obtained from marrow, mobilized peripheral blood, and umbilical cord blood. Mesenchymal stem cells (MSCs) are traditionally isolated from marrow. Bone marrow-derived MSCs (BM-MSCs) have previously demonstrated their ability to act as a feeder layer in support of ex vivo cord blood expansion. However, the use of BM-MSCs to support the growth, differentiation, and engraftment of cord blood may not be ideal for transplant purposes. Therefore, the potential of MSCs from a novel source, the Wharton's jelly of umbilical cords, to act as stromal support for the long-term culture of cord blood HSC was evaluated. Umbilical cord-derived MSCs (UC-MSCs) were cultured from the Wharton's jelly of umbilical cord segments. The UC-MSCs were then profiled for expression of 12 cell surface receptors and tested for their ability to support cord blood HSCs in a long-term culture-initiating cell (LTC-IC) assay. Upon culture, UC-MSCs express a defined set of cell surface markers (CD29, CD44, CD73, CD90, CD105, CD166, and HLA-A) and lack other markers (CD45, CD34, CD38, CD117, and HLA-DR) similar to BM-MSCs. Like BM-MSCs, UC-MSCs effectively support the growth of CD34+ cord blood cells in LTC-IC assays. These data suggest the potential therapeutic application of Wharton's jelly-derived UC-MSCs to provide stromal support structure for the long-term culture of cord blood HSCs as well as the possibility of cotransplantation of genetically identical, HLA-matched, or unmatched cord blood HSCs and UC-MSCs in the setting of HSC transplantation.

Hematopoietic Stem Cells in Neonates: Any Differences between Very Preterm and Term Neonates?

PubMed Central

Wisgrill, Lukas; Schüller, Simone; Bammer, Markus; Berger, Angelika; Pollak, Arnold; Radke, Teja Falk; Kögler, Gesine; Spittler, Andreas; Helmer, Hanns; Husslein, Peter; Gortner, Ludwig

2014-01-01

Background In the last decades, human full-term cord blood was extensively investigated as a potential source of hematopoietic stem and progenitor cells (HSPCs). Despite the growing interest of regenerative therapies in preterm neonates, only little is known about the biological function of HSPCs from early preterm neonates under different perinatal conditions. Therefore, we investigated the concentration, the clonogenic capacity and the influence of obstetric/perinatal complications and maternal history on HSPC subsets in preterm and term cord blood. Methods CD34+ HSPC subsets in UCB of 30 preterm and 30 term infants were evaluated by flow cytometry. Clonogenic assays suitable for detection of the proliferative potential of HSPCs were conducted. Furthermore, we analyzed the clonogenic potential of isolated HSPCs according to the stem cell marker CD133 and aldehyde dehydrogenase (ALDH) activity. Results Preterm cord blood contained a significantly higher concentration of circulating CD34+ HSPCs, especially primitive progenitors, than term cord blood. The clonogenic capacity of HSPCs was enhanced in preterm cord blood. Using univariate analysis, the number and clonogenic potential of circulating UCB HSPCs was influenced by gestational age, birth weight and maternal age. Multivariate analysis showed that main factors that significantly influenced the HSPC count were maternal age, gestational age and white blood cell count. Further, only gestational age significantly influenced the clonogenic potential of UCB HSPCs. Finally, isolated CD34+/CD133+, CD34+/CD133– and ALDHhigh HSPC obtained from preterm cord blood showed a significantly higher clonogenic potential compared to term cord blood. Conclusion We demonstrate that preterm cord blood exhibits a higher HSPC concentration and increased clonogenic capacity compared to term neonates. These data may imply an emerging use of HSPCs in autologous stem cell therapy in preterm neonates. PMID:25181353

IFNy+ and IFNy- Treg subsets with stable and unstable Foxp3 expression in kidney transplant recipients with good long-term graft function.

PubMed

Trojan, Karina; Unterrainer, Christian; Aly, Mostafa; Zhu, Li; Weimer, Rolf; Bulut, Nuray; Morath, Christian; Opelz, Gerhard; Daniel, Volker

2016-10-29

Treg are a heterogenous cell population. In the present study we attempted to identify Treg subsets that might contribute to stable and good long-term graft function. Lymphocyte and Treg subsets were studied in 136 kidney transplant recipients with good long-term graft function and in 52 healthy control individuals using eight-color-fluorescence flow cytometry. Foxp3 TSDR methylation status was investigated in enriched IFNy+ and IFNy- Treg preparations using high resolution melt analysis. Compared with healthy controls, patients showed strong associations of IFNy secreting Helios+ and Helios- Treg with Treg that co-expressed perforin and/or CTLA4 (CD152; p<0.01). Moreover they showed associations of IFNy-Helios+ Treg with Treg that produced TGFβ and/or perforin and of IFNy-Helios- Treg with TGFβ production (all p<0.01). Only in patients, but not in healthy controls, were IFNy- Helios+ and Helios- Treg associated with higher CD45+, CD3+, (CD4+), CD19+ lymphocyte counts (p<0.001). In addition IFNy-Helios+ Treg were associated with CD16+56+ lymphocytes (p<0.001). Enriched IFNy- Treg from female but not male patients showed an association of Foxp3 methylation with higher total Treg and higher Helios+IFNy-, CXCR3+Lselectin+ (CD183+CD62L+), CXCR3-Lselectin+ and CD28+HLADR+ Treg subsets (p<0.01). Enriched IFNy+ Treg from male patients showed an association of demethylated Foxp3 with total Treg and IL10-TFGβ+ Treg counts, and in enriched IFNy- Treg an association of methylated Foxp3 with APO1/FasR+FasL+ (CD95+CD178+) Treg (p<0.01). Kidney recipients with good long-term graft function possess IFNy+ and IFNy- Treg with stable and unstable Foxp3 expression in the blood. They co-express CD28, HLADR, CTLA4, CXCR3, Lselectin, TGFβ, perforin and FasL and might contribute to the establishment and maintenance of good long-term graft function. Copyright © 2016. Published by Elsevier B.V.

Lethal and sublethal effects of chlorine, phenol, and chlorine-phenol mixtures on the mud crab, Panopeus herbstii.

PubMed

Key, P B; Scott, G I

1986-11-01

The mud crab, Panopeus herbstii, was acutely exposed (96-hr) to chlorine-produced oxidants (CPO), phenol, and a CPO-phenolic mixture (1:1) to determine lethal and sublethal effects. The 96-hr (LC50) values were determined for each individual compound and mixture. Additionally, whole-animal respiration rates were measured following acute exposure to sublethal concentrations of each compound or mixture. Phenol uptake/depuration rates were measured in the phenol and CPO-phenol mixture concentrations. Results indicated 96-hr LC50 values of 1.06 mg/L for CPO (fiducial limits (FL) = 0.53-2.01 mg/L), 52.8 mg/L for phenol (FL = 45.6-64.5 mg/L), and 184.7 mg/L total toxicant units (TTU) for the CPO-phenol mixture (FL = 143.7-250.2 mg/L TTU). Statistical analysis indicated that the acute toxicity of the CPO-phenol mixture was less than additive. Sublethal studies indicated that only acute exposure to sublethal concentrations of CPO caused altered respiration rates. After 96-hr depuration, metabolic rates in all CPO-exposure crabs generally returned to control rates. Uptake/depuration rate studies indicated significantly lower phenol uptake rates in crabs exposed to the CPO-phenol mixture. These findings suggest that the less-than-additive toxicity of the CPO-phenol mixture may result from lowered uptake/depuration rate kinetics and indicate that the discharge of chlorinated-phenolic waste may not result in additive and/or synergistic interactions, but rather in less-than-additive effects on decapod aquatic species.

Spinosad- and Deltamethrin-Induced Impact on Mating and Reproductive Output of the Maize Weevil Sitophilus zeamais.

PubMed

Vélez, Mayra; Botina, Lorena L; Turchen, Leonardo M; Barbosa, Wagner F; Guedes, Raul Narciso C

2018-04-02

Assessments of acute insecticide toxicity frequently focus on the lethal effects on individual arthropod pest species and populations neglecting the impacts and consequences of sublethal exposure. However, the sublethal effects of insecticides may lead to harmful, neutral, or even beneficial responses that may affect (or not) the behavior and sexual fitness of the exposed insects. Intriguingly, little is known about such effects on stored product insect pests in general and the maize weevil in particular. Thus, we assessed the sublethal effects of spinosad and deltamethrin on female mate-searching, mating behavior, progeny emergence, and grain consumption by maize weevils. Insecticide exposure did not affect the resting time, number of stops, and duration of mate-searching by female weevils, but their walking velocity was compromised. Maize weevil couples sublethally exposed to deltamethrin and spinosad exhibited altered reproductive behavior (walking, interacting, mounting, and copulating), but deltamethrin caused greater impairment. Curiously, higher grain consumption and increased progeny emergence were observed in deltamethrin-exposed insects, suggesting that this pyrethroid insecticide elicits hormesis in maize weevils that may compromise control efficacy by this compound. Although spinosad has less of an impact on weevil reproductive behavior than deltamethrin, this bioinsecticide also benefited weevil progeny emergence, but did not affect grain consumption. Therefore, our findings suggest caution using either compound, and particularly deltamethrin, for controlling the maize weevil, as they may actually favor this species population growth when in sublethal exposure requiring further assessments. The same concern may be valid for other insecticides as well, what deserves future attention.

Crop-emptying rate and the design of pesticide risk assessment schemes in the honey bee and wild bees (Hymenoptera: Apidae).

PubMed

Fournier, Alice; Rollin, Orianne; Le Féon, Violette; Decourtye, Axel; Henry, Mickaël

2014-02-01

Recent scientific literature and reports from official sanitary agencies have pointed out the deficiency of current pesticide risk assessment processes regarding sublethal effects on pollinators. Sublethal effects include troubles in learning performance, orientation skills, or mobility, with possible contribution to substantial dysfunction at population scale. However, the study of sublethal effects is currently limited by considerable knowledge gaps, particularly for the numerous pollinators other than the honey bee Apis mellifera L.--the traditional model for pesticide risk assessment in pollinators. Here, we propose to use the crop-emptying time as a rule of thumb to guide the design of oral exposure experiments in the honey bee and wild bees. The administration of contaminated sucrose solutions is typically followed by a fasting time lapse to allow complete assimilation before the behavioral tests. The fasting duration should at least encompass the crop-emptying time, because no absorption takes place in the crop. We assessed crop-emptying rate in fasted bees and how it relates 1) with sucrose solution concentration in the honey bee and 2) with body mass in wild bees. Fasting duration required for complete crop emptying in honey bees fed 20 microl of a 50% sucrose solution was nearly 2 h. Actual fasting durations are usually shorter in toxicological studies, suggesting incomplete crop emptying, and therefore partial assimilation of experimental solutions that could imply underestimation of sublethal effects. We also found faster crop-emptying rates in large wild bees compared with smaller wild bees, and suggest operative rules to adapt sublethal assessment schemes accordingly.

Sublethal Triclosan Exposure Decreases Susceptibility to Gentamicin and Other Aminoglycosides in Listeria monocytogenes▿

PubMed Central

Christensen, Ellen G.; Gram, Lone; Kastbjerg, Vicky G.

2011-01-01

The human food-borne pathogen Listeria monocytogenes is capable of persisting in food processing plants despite cleaning and sanitation and is likely exposed to sublethal biocide concentrations. This could potentially affect susceptibility of the bacterium to biocides and other antimicrobial agents. The purpose of the present study was to determine if sublethal biocide concentrations affected antibiotic susceptibility in L. monocytogenes. Exposure of L. monocytogenes strains EGD and N53-1 to sublethal concentrations of Incimaxx DES (containing peroxy acids and hydrogen peroxide) and Triquart Super (containing quaternary ammonium compound) in four consecutive cultures did not alter the frequency of antibiotic-tolerant isolates, as determined by plating on 2× the MIC for a range of antibiotics. Exposure of eight strains of L. monocytogenes to 1 and 4 μg/ml triclosan did not alter triclosan sensitivity. However, all eight strains became resistant to gentamicin (up to 16-fold increase in MIC) after exposure to sublethal triclosan concentrations. Gentamicin-resistant isolates of strains N53-1 and 4446 were also resistant to other aminoglycosides, such as kanamycin, streptomycin, and tobramycin. Gentamicin resistance remained at a high level also after five subcultures without triclosan or gentamicin. Aminoglycoside resistance can be caused by mutations in the target site, the 16S rRNA gene. However, such mutations were not detected in the N53-1-resistant isolates. A combination of gentamicin and ampicillin is commonly used in listeriosis treatment. The triclosan-induced resistance is, hence, of great concern. Further investigations are needed to determine the molecular mechanisms underlying the effect of triclosan. PMID:21746948

Azadirachtin-induced hormesis mediating shift in fecundity-longevity trade-off in the Mexican bean weevil (Chrysomelidae: Bruchinae).

PubMed

Mallqui, K S Vilca; Vieira, J L; Guedes, R N C; Gontijo, L M

2014-04-01

Insecticides can have lethal or sublethal effects upon targeted pest species, and sublethal effects may even favor pest outbreaks if insecticide-induced hormesis occurs. Hormesis is a biphasic dose-response of a given chemical compound that is stimulatory at low doses and toxic at high doses. The former response may result from the disruption of animal homeostasis leading to trade-off shifts between basic ecophysiological processes. A growing interest in the use of biorational insecticides, such as azadirachtin to control stored-product pests, raises concerns about potential sublethal effects. In this study, we explored the hypothesis that azadirachtin can negatively impact the reproductive capacity of the Mexican bean weevil, Zabrotes subfasciatus (Boheman) (Chrysomelidae: Bruchinae), a key pest of stored beans. In addition, we investigated whether adults of this species could compensate for any sublethal effect that might have affected any of their reproductive parameters by adjusting the allocation of its reproductive efforts. The results showed that females of Z. subfasciatus increased fecundity daily to compensate for azadirachtin-induced decreased longevity. In addition, a stage-structured matrix study revealed that populations of Z. subfasciatus engendered from females exposed to azadirachtin exhibited a higher rate of population increase (r) and a higher net reproductive rate (R(o)). Finally, a projection matrix analysis showed notably higher densities along the generations for azadirachtin-exposed Z. subfasciatus populations. Thus, our study provides empirical evidence for the capacity of Z. subfasciatus to adapt to sublethal effects caused by biorational insecticides; consequently, this study highlights the importance of understanding this phenomenon when devising pest management strategies.

CD8+ T Cells Primed in the Periphery Provide Time-Bound Immune-Surveillance to the Central Nervous System

PubMed Central

Young, Kevin G.; MacLean, Susanne; Dudani, Renu; Krishnan, Lakshmi; Sad, Subash

2016-01-01

After vaccination, memory CD8+ T cells migrate to different organs to mediate immune surveillance. In most nonlymphoid organs, following an infection, CD8+ T cells differentiate to become long-lived effector-memory cells, thereby providing long-term protection against a secondary infection. In this study, we demonstrated that Ag-specific CD8+ T cells that migrate to the mouse brain following a systemic Listeria infection do not display markers reminiscent of long-term memory cells. In contrast to spleen and other nonlymphoid organs, none of the CD8+ T cells in the brain reverted to a memory phenotype, and all of the cells were gradually eliminated. These nonmemory phenotype CD8+ T cells were found primarily within the choroid plexus, as well as in the cerebrospinal fluid-filled spaces. Entry of these CD8+ T cells into the brain was governed primarily by CD49d/VCAM-1, with the majority of entry occurring in the first week postinfection. When CD8+ T cells were injected directly into the brain parenchyma, cells that remained in the brain retained a highly activated (CD69hi) phenotype and were gradually lost, whereas those that migrated out to the spleen were CD69low and persisted long-term. These results revealed a mechanism of time-bound immune surveillance to the brain by CD8+ T cells that do not reside in the parenchyma. PMID:21715683

DIFFERENTIAL RESPONSE TO ALLOGENIC AND XENOGENIC SKIN GRAFTS BY SUBLETHALLY IRRADIATED (670 RAD) AND NON-IRRADIATED MICE SENSITIZED BY VARIOUS MEANS

DTIC Science & Technology

consecutive BALB/c or rat skin tail grafts. One week following the last injection or the rejection of the second, skin graft , the mice either were grafted...resulted in prolonged survival of subsequent allogenic skin grafts in sublethally irradiated mice. The second-set response to a xenogenic skin graft was

DIFFERENTIAL EFFECTS OF SPECIFIC ANTISERA ON THE REJECTION OF ALLOGENIC AND XENOGENIC SKIN GRAFTS BY SUBLETHALLY X-IRRADIATED MICE

DTIC Science & Technology

an allogenic skin graft can be significantly inhibited, in sublethally irrsdiated mice, by specific antisera, while the first-set response to a...xenogenic skin graft remains resistant to similar treatient. Specific antisera had no effect upon a pre-existing second-set response. The significance of these data is discussed.

Physiological stress and ethanol accumulation in tree stems and woody tissues at sublethal temperatures from fire

Treesearch

Rick G. Kelsey; Douglas J. Westlind

2017-01-01

The lethal temperature limit is 60 degrees Celsius (°C) for plant tissues, including trees, with lower temperatures causing heat stress. As fire injury increases on tree stems, there is an accompanying rise in tissue ethanol concentrations, physiologically linked to impaired mitochondrial oxidative phosphorylation energy production. We theorize that sublethal tissue...

Transmission electron microscopy study of Listeria monocytogenes serotype 1/2a cells exposed to sublethal heat stress and carvacrol

USDA-ARS?s Scientific Manuscript database

The objective of this study was to investigate the morphological changes that occurred in Listeria monocytogenes serotype 1/2a cells as visualized by transmission electron microscopy (TEM) after exposure to sublethal heat stress at 48°C for 60 min and in combination with lethal concentration of carv...

A flowthrough fecundity test with Nitocra spinipes (Harpacticoidea Crustacea) for aquatic toxicity.

PubMed

Bengtsson, B E; Bergström, B

1987-12-01

A sublethal flowthrough fecundity test with the euryhaline harpacticoid copepod Nitocra spinipes has been developed as a complement to the acute toxicity test (for 48 or 96 hr LC50) with the same species (B-E. Bengtsson, 1981, Mar. Pollut. Biol. 9,238-241). Bacterial suspension as feed and test water are continuously fed by a peristaltic pump to the system. Newly fertilized females with ovigerous bands are harvested from laboratory cultures and put into the test vessels at the start of the experiment. They are then exposed to a series of concentrations of chemicals or industrial effluents for 13 days. The amount of live offspring (metanauplia and copepodids) are recorded and an EC50 for fecundity is calculated. The report gives a detailed technical description of the test system and presents the results from 11 tests with pure chemicals (Zn, Cd, As, and pentachlorophenate) and six industrial effluents (pulp industry, textile industry, and refinery) in salinities ranging from 3 to 25%.

Sublethal effects of spirodiclofen, abamectin and pyridaben on life-history traits and life-table parameters of two-spotted spider mite, Tetranychus urticae (Acari: Tetranychidae).

PubMed

Saber, Moosa; Ahmadi, Zeinab; Mahdavinia, Gholamreza

2018-05-01

Two-spotted spider mite, Tetranychus urticae Koch, is one of the economically most important pests on a wide range of crops in greenhouses and orchards worldwide. Control of T. urticae has been largely based on the use of acaricides. Sublethal effects of spirodiclofen, pyridaben and abamectin were studied on life-table parameters of T. urticae females treated with the acaricides. LC 25 values of spirodiclofen, abamectin and pyridaben (3.84, 0.04 and 136.96 µg a.i./ml, respectively) were used for sublethal studies. All acaricides showed significant effects on T. urticae biological parameters including developmental time, survival rate, and fecundity. The females treated with spirodiclofen, abamectin and pyridaben at LC 25 exhibited significantly reduced net reproductive rate (R 0 ), finite rate of increase (λ) and intrinsic rate of increase (r). The intrinsic rate of increase in spirodiclofen, abamectin and pyridaben treated groups and control were 0.0138, 0.0273, 0.039 and 0.2481 female offspring per female per day, respectively. The results indicated that sublethal concentrations of tested pesticides strongly affected the life characteristics of spider mite and consequently may influence mite population growth in future generations.

Alternative control of Aedes aegypti resistant to pyrethroids: lethal and sublethal effects of monoterpene bioinsecticides.

PubMed

Silva, Indira Ma; Martins, Gustavo F; Melo, Carlisson R; Santana, Alisson S; Faro, Ruan Rn; Blank, Arie F; Alves, Péricles B; Picanço, Marcelo C; Cristaldo, Paulo F; Araújo, Ana Paula A; Bacci, Leandro

2018-04-01

The mosquito Aedes aegypti is intensively controlled because it is a vector of viruses that cause numerous diseases, especially in tropical regions. As a consequence of the indiscriminate use of insecticides, populations from different regions have become resistant to pyrethroids. Here, we analyzed the lethal and sublethal effects of essential oil of Aristolochia trilobata and its major compounds on A. aegypti from susceptible and pyrethroid-resistant populations. Our results showed that the toxicity of the different compounds and behavioral changes in response to them are dependent on the stage of the insect life cycle. The monoterpene ρ-cymene caused high mortality in both larvae and adult females of A. aegypti, including those from the pyrethroid-resistant population. The monoterpenes limonene and linalool caused a sublethal effect in the larvae, triggering changes in the swimming pattern. This study highlights the potential of the essential oil of A. trilobata and its major compounds ρ-cymene and limonene for the control of A. aegypti and reveals the importance of analyzing sublethal effects on the population dynamics of the A. aegypti mosquito. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Costs and benefits of sublethal Drosophila C virus infection.

PubMed

Gupta, V; Stewart, C O; Rund, S S C; Monteith, K; Vale, P F

2017-07-01

Viruses are major evolutionary drivers of insect immune systems. Much of our knowledge of insect immune responses derives from experimental infections using the fruit fly Drosophila melanogaster. Most experiments, however, employ lethal pathogen doses through septic injury, frequently overwhelming host physiology. While this approach has revealed several immune mechanisms, it is less informative about the fitness costs hosts may experience during infection in the wild. Using both systemic and oral infection routes, we find that even apparently benign, sublethal infections with the horizontally transmitted Drosophila C virus (DCV) can cause significant physiological and behavioural morbidity that is relevant for host fitness. We describe DCV-induced effects on fly reproductive output, digestive health and locomotor activity, and we find that viral morbidity varies according to the concentration of pathogen inoculum, host genetic background and sex. Notably, sublethal DCV infection resulted in a significant increase in fly reproduction, but this effect depended on host genotype. We discuss the relevance of sublethal morbidity for Drosophila ecology and evolution, and more broadly, we remark on the implications of deleterious and beneficial infections for the evolution of insect immunity. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

PFOS, PFNA, and PFOA Sub-Lethal Exposure to Embryonic Zebrafish Have Different Toxicity Profiles in Terms of Morphometrics, Behavior and Gene Expression

PubMed Central

Jantzen, Carrie E.; Annunziato, Kate A.; Bugel, Sean M.; Cooper, Keith R.

2016-01-01

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 µM – 2.0 µM; 20–2000 ppb) 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, 2.0 µM) 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. PMID:27058923

Effects of field-realistic doses of glyphosate on honeybee appetitive behaviour.

PubMed

Herbert, Lucila T; Vázquez, Diego E; Arenas, Andrés; Farina, Walter M

2014-10-01

Glyphosate (GLY) is a broad-spectrum herbicide used for weed control. The sub-lethal impact of GLY on non-target organisms such as insect pollinators has not yet been evaluated. Apis mellifera is the main pollinator in agricultural environments and is a well-known model for behavioural research. Honeybees are also accurate biosensors of environmental pollutants and their appetitive behavioural response is a suitable tool with which to test sub-lethal effects of agrochemicals. We studied the effects of field-realistic doses of GLY on honeybees exposed chronically or acutely to the herbicide. We focused on sucrose sensitivity, elemental and non-elemental associative olfactory conditioning of the proboscis extension response (PER), and foraging-related behaviour. We found a reduced sensitivity to sucrose and learning performance for the groups chronically exposed to GLY concentrations within the range of recommended doses. When olfactory PER conditioning was performed with sucrose reward with the same GLY concentrations (acute exposure), elemental learning and short-term memory retention decreased significantly compared with controls. Non-elemental associative learning was also impaired by an acute exposure to GLY traces. Altogether, these results imply that GLY at concentrations found in agro-ecosystems as a result of standard spraying can reduce sensitivity to nectar reward and impair associative learning in honeybees. However, no effect on foraging-related behaviour was found. Therefore, we speculate that successful forager bees could become a source of constant inflow of nectar with GLY traces that could then be distributed among nestmates, stored in the hive and have long-term negative consequences on colony performance. © 2014. Published by The Company of Biologists Ltd.

Effects of the brominated flame retardants hexabromocyclododecane (HBCDD), and tetrabromobisphenol A (TBBPA), on hepatic enzymes and other biomarkers in juvenile rainbow trout and feral eelpout.

PubMed

Ronisz, D; Finne, E Farmen; Karlsson, H; Förlin, L

2004-08-25

Brominated flame retardants (BFRs) leak out in the environment, including the aquatic one. Despite this, sublethal effects of these chemicals are poorly investigated in fish. In this study, a screening of selected biomarkers in juvenile rainbow trout (Oncorhynchus mykiss) and feral eelpout (Zoarces viviparus) was performed after exposure to hexabromocyclododecane (HBCDD) and tetrabromobisphenol A (TBBPA). Rainbow trout was injected intraperitoneally (i.p.) with HBCDD or TBBPA. Two out of four short-term experiments with HBCDD showed an increase in the activity of catalase. A 40% increase in liver somatic index (LSI) could be observed after 28 days. HBCDD did also seem to have an inhibitory effect on CYP1A's activity (ethoxyresorufin-O-deethylase (EROD)). A putative peroxisome proliferating activity of the compound was investigated without giving a definite answer. HBCDD did not seem to be estrogenic or genotoxic. TBBPA increased the activity of glutathione reductase (GR) after 4, 14 and 28 days in rainbow trout suggesting a possible role of this compound in inducing oxidative stress. The compound did not seem to be estrogenic. TBBPA seemed to compete with the artificial substrate ethoxyresorufin in vitro, during the EROD assay. In eelpout, only one 5 days in vivo experiment was performed. Neither of the compounds gave rise to any effect in this fish. This was the first screening of sublethal effects of the two chemicals in fish, using high doses. Our results indicate that there is a need for further studies of long-term, low-dose effects of these two widely used flame retardants.

Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors.

PubMed

Kochenderfer, James N; Rosenberg, Steven A

2013-05-01

Most B-cell malignancies express CD19, and a majority of patients with B-cell malignancies are not cured by current standard therapies. Chimeric antigen receptors (CARs) are fusion proteins consisting of antigen recognition moieties and T-cell activation domains. T cells can be genetically modified to express CARs, and adoptive transfer of anti-CD19 CAR T cells is now being tested in clinical trials. Effective clinical treatment with anti-CD19 CAR T cells was first reported in 2010 after a patient with advanced-stage lymphoma treated at the NCI experienced a partial remission of lymphoma and long-term eradication of normal B cells. Additional patients have subsequently obtained long-term remissions of advanced-stage B-cell malignancies after infusions of anti-CD19 CAR T cells. Long-term eradication of normal CD19(+) B cells from patients receiving infusions of anti-CD19 CAR T cells demonstrates the potent antigen-specific activity of these T cells. Some patients treated with anti-CD19 CAR T cells have experienced acute adverse effects, which were associated with increased levels of serum inflammatory cytokines. Although anti-CD19 CAR T cells are at an early stage of development, the potent antigen-specific activity observed in patients suggests that infusions of anti-CD19 CAR T cells might become a standard therapy for some B-cell malignancies.

Recognition of prostate-specific antigenic peptide determinants by human CD4 and CD8 T cells.

PubMed

Corman, J M; Sercarz, E E; Nanda, N K

1998-11-01

It is now becoming accepted that one is not tolerant to all the determinants of self proteins: the T cell repertoire directed to some sequences in self proteins is intact and can be activated. When a self protein is exclusively expressed by tumour cells, the T cell repertoire directed to the particular self antigen can potentially be activated to attack the tumour: this would amount to induction of a beneficial autoimmune response. Prostate cancer offers a unique opportunity for activation of a tumour-specific immune response owing to the exclusive synthesis of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) by prostatic tissue and prostate tumour cells. In this study we examine the CD4 and CD8 T cell repertoires specific for peptides of PSA and PSM in normal human male individuals, using short-term, peptide antigen-driven CD4 and CD8 T cell lines. We show that short-term, CD4 T cell lines derived from six HLA-DR4 individuals showed strong proliferative responses to six of 10 tested peptides of PSA, selected as to contain a DR4 binding motif. Short-term, CD8 T cell lines from three HLA-A1 individuals showed specific cytolytic activity for autologous targets loaded with five of five tested peptides of PSA and PSM, selected to possess an HLA-A1 binding motif. One of the peptides chosen is termed a 'dual-motif' peptide, as it encodes determinants for both CD4 and CD8 T cells. These results, indicating the existence of CD4 and CD8 T cells against determinants of the self proteins, PSA and PSM, in healthy male individuals reveal the potential of the T cell repertoire from the typical prostate cancer patient to eradicate prostate tumours upon being appropriately activated.

Thrombopoietin treatment of one graft in a double cord blood transplant provides early platelet recovery while contributing to long-term engraftment in NSG mice.

PubMed

van der Garde, Mark; van Hensbergen, Yvette; Brand, Anneke; Slot, Manon C; de Graaf-Dijkstra, Alice; Mulder, Arend; Watt, Suzanne M; Zwaginga, Jaap Jan

2015-01-01

Human cord blood (CB) hematopoietic stem cell (HSC) transplants demonstrate delayed early neutrophil and platelet recovery and delayed longer term immune reconstitution compared to bone marrow and mobilized peripheral blood transplants. Despite advances in enhancing early neutrophil engraftment, platelet recovery after CB transplantation is not significantly altered when compared to contemporaneous controls. Recent studies have identified a platelet-biased murine HSC subset, maintained by thrombopoietin (TPO), which has enhanced capacity for short- and long-term platelet reconstitution, can self-renew, and can give rise to myeloid- and lymphoid-biased HSCs. In previous studies, we have shown that transplantation of human CB CD34(+) cells precultured in TPO as a single graft accelerates early platelet recovery as well as yielding long-term repopulation in immune-deficient mice. In this study, using a double CB murine transplant model, we investigated whether TPO cultured human CB CD34(+) cells have a competitive advantage or disadvantage over untreated human CB CD34(+) cells in terms of (1) short-term and longer term platelet recovery and (2) longer term hematological recovery. Our studies demonstrate that the TPO treated graft shows accelerated early platelet recovery without impairing the platelet engraftment of untreated CD34(+) cells. Notably, this was followed by a dominant contribution to platelet production through the untreated CD34(+) cell graft over the intermediate to longer term. Furthermore, although the contribution of the TPO treated graft to long-term hematological engraftment was reduced, the TPO treated and untreated grafts both contributed significantly to long-term chimerism in vivo.

Transition of late-stage effector T cells to CD27+ CD28+ tumor-reactive effector memory T cells in humans after adoptive cell transfer therapy

PubMed Central

Powell, Daniel J.; Dudley, Mark E.; Robbins, Paul F.; Rosenberg, Steven A.

2007-01-01

In humans, the pathways of memory T-cell differentiation remain poorly defined. Recently, adoptive cell transfer (ACT) of tumor-reactive T lymphocytes to metastatic melanoma patients after nonmyeloablative chemotherapy has resulted in persistence of functional, tumor-reactive lymphocytes, regression of disease, and induction of melanocyte-directed autoimmunity in some responding patients. In the current study, longitudinal phenotypic analysis was performed on melanoma antigen–specific CD8+ T cells during their transition from in vitro cultured effector cells to long-term persistent memory cells following ACT to 6 responding patients. Tumor-reactive T cells used for therapy were generally late-stage effector cells with a CD27Lo CD28Lo CD45RA− CD62 ligand− (CD62L−) CC chemokine receptor 7− (CCR7−) interleukin-7 receptor αLo (IL-7RαLo) phenotype. After transfer, rapid up-regulation and continued expression of IL-7Rα in vivo suggested an important role for IL-7R in immediate and long-term T-cell survival. Although the tumor antigen–specific T-cell population contracted between 1 and 4 weeks after transfer, stable numbers of CD27+ CD28+ tumor-reactive T cells were maintained, demonstrating their contribution to the development of long-term, melanoma-reactive memory CD8+ T cells in vivo. At 2 months after transfer, melanoma-reactive T cells persisted at high levels and displayed an effector memory phenotype, including a CD27+ CD28+ CD62L− CCR7− profile, which may explain in part their ability to mediate tumor destruction. PMID:15345595

Consumer direction in long-term care policy: overcoming barriers to promoting older adults' opportunity for self-direction.

PubMed

Ruggiano, Nicole

2012-01-01

There has been a growing trend in long-term care policy to offer individuals with disabilities the option of consumer direction (CD), where responsibility of managing care and support services is transferred from agencies to care recipients, thus supporting clients' self-determination. Although CD has been accepted as an option for non-elderly individuals with disabilities, barriers persist to promoting older adults' autonomy through CD. This article reviews the incorporation of CD in long-term care policy, addresses the current barriers to providing older adults the right to self-direct, and makes recommendations for overcoming these barriers through social work practice, policy, and research.

Promoting long-term survival of insulin-producing cell grafts that differentiate from adipose tissue-derived stem cells to cure type 1 diabetes.

PubMed

Zhang, Shuzi; Dai, Hehua; Wan, Ni; Moore, Yolonda; Dai, Zhenhua

2011-01-01

Insulin-producing cell clusters (IPCCs) have recently been generated in vitro from adipose tissue-derived stem cells (ASCs) to circumvent islet shortage. However, it is unknown how long they can survive upon transplantation, whether they are eventually rejected by recipients, and how their long-term survival can be induced to permanently cure type 1 diabetes. IPCC graft survival is critical for their clinical application and this issue must be systematically addressed prior to their in-depth clinical trials. Here we found that IPCC grafts that differentiated from murine ASCs in vitro, unlike their freshly isolated islet counterparts, did not survive long-term in syngeneic mice, suggesting that ASC-derived IPCCs have intrinsic survival disadvantage over freshly isolated islets. Indeed, β cells retrieved from IPCC syngrafts underwent faster apoptosis than their islet counterparts. However, blocking both Fas and TNF receptor death pathways inhibited their apoptosis and restored their long-term survival in syngeneic recipients. Furthermore, blocking CD40-CD154 costimulation and Fas/TNF signaling induced long-term IPCC allograft survival in overwhelming majority of recipients. Importantly, Fas-deficient IPCC allografts exhibited certain immune privilege and enjoyed long-term survival in diabetic NOD mice in the presence of CD28/CD40 joint blockade while their islet counterparts failed to do so. Long-term survival of ASC-derived IPCC syngeneic grafts requires blocking Fas and TNF death pathways, whereas blocking both death pathways and CD28/CD40 costimulation is needed for long-term IPCC allograft survival in diabetic NOD mice. Our studies have important clinical implications for treating type 1 diabetes via ASC-derived IPCC transplantation. © 2011 Zhang et al.

Promoting Long-Term Survival of Insulin-Producing Cell Grafts That Differentiate from Adipose Tissue-Derived Stem Cells to Cure Type 1 Diabetes

PubMed Central

Zhang, Shuzi; Dai, Hehua; Wan, Ni; Moore, Yolonda; Dai, Zhenhua

2011-01-01

Background Insulin-producing cell clusters (IPCCs) have recently been generated in vitro from adipose tissue-derived stem cells (ASCs) to circumvent islet shortage. However, it is unknown how long they can survive upon transplantation, whether they are eventually rejected by recipients, and how their long-term survival can be induced to permanently cure type 1 diabetes. IPCC graft survival is critical for their clinical application and this issue must be systematically addressed prior to their in-depth clinical trials. Methodology/Principal Findings Here we found that IPCC grafts that differentiated from murine ASCs in vitro, unlike their freshly isolated islet counterparts, did not survive long-term in syngeneic mice, suggesting that ASC-derived IPCCs have intrinsic survival disadvantage over freshly isolated islets. Indeed, β cells retrieved from IPCC syngrafts underwent faster apoptosis than their islet counterparts. However, blocking both Fas and TNF receptor death pathways inhibited their apoptosis and restored their long-term survival in syngeneic recipients. Furthermore, blocking CD40-CD154 costimulation and Fas/TNF signaling induced long-term IPCC allograft survival in overwhelming majority of recipients. Importantly, Fas-deficient IPCC allografts exhibited certain immune privilege and enjoyed long-term survival in diabetic NOD mice in the presence of CD28/CD40 joint blockade while their islet counterparts failed to do so. Conclusions/Significance Long-term survival of ASC-derived IPCC syngeneic grafts requires blocking Fas and TNF death pathways, whereas blocking both death pathways and CD28/CD40 costimulation is needed for long-term IPCC allograft survival in diabetic NOD mice. Our studies have important clinical implications for treating type 1 diabetes via ASC-derived IPCC transplantation. PMID:22216347

Effects of Sublethal Concentrations of the Chitin Synthesis Inhibitor, Hexaflumuron, on the Development and Hemolymph Physiology of the Cutworm, Spodoptera litura

PubMed Central

Zhu, Qiqi; He, Yuan; Yao, Jing; Liu, Yinzhao; Tao, Liming; Huang, Qingchun

2012-01-01

The effects of sublethal concentrations 0.1, 0.5, and 1.2 µg mL-1of the chitin synthesis inhibitor, hexaflumuron, on larval growth and development, the count and proportion of hemocytes, and carbohydrate content (trehalose and glyceride) in hemolymph were investigated in the cutworm, Spodoptera litura (Fabricious) (Lepidoptera: Noctuidae). When 3rdinstar larvae were subjected to the sublethal concentrations, there were dose-dependent effects on larval weight and length of each instar larvae, percent pupation and the duration of development. Most of the larvae died during the molting process at all concentrations. Few individuals from 0.5 and 1.2 µg mL -1concentrations could develop to the 6thinstar, while the pupae emerging from the 0.1 µg mL -1concentrations did not exceed 16% of the number of the initial larvae. In 5thinstar S. litura, the total number of hemocytes was significantly increased at 24 hours post—treatment, whereas the proliferation of hemocytes was inhibited, plasmatocyte pseudopodia contracted, and granulocyte expanded at 96 hours post—treatment. The increases of plasmatocyte count and the decreases of granulocyte count were dose—dependent. The longer treatment time of the sublethal concentrations increased the content of total carbohydrate and trehalose in hematoplasma, and was dose—dependent in hemocytes. The content of glyceride in hemolymph was significantly higher at 24 hours post—treatment, but gradually returned to normal levels at 96 hours post—treatment as compared with the control. The results suggested that sublethal concentrations of hexaflumuron reduced S. litura larval survival and interfered with hemolymph physiological balances. PMID:22958164

Prey Foraging Under Sublethal Lambda-Cyhalothrin Exposure on Pyrethroid-Susceptible and -Resistant Lady Beetles (Eriopis connexa (Coleoptera: Coccinelidae)).

PubMed

D'Ávila, V A; Reis, L C; Barbosa, W F; Cutler, G C; Torres, J B; Guedes, R N C

2018-05-28

Sublethal insecticide exposure may affect foraging of insects, including natural enemies, although the subject is usually neglected. The lady beetle Eriopis connexa (Germar, 1824) (Coleoptera: Coccinelidae) is an important predator of aphids with existing pyrethroid-resistant populations that are undergoing scrutiny for potential use in pest management systems characterized by frequent insecticide use. However, the potential effect of sublethal pyrethroid exposure on this predator's foraging activity has not yet been assessed and may compromise its use in biological control. Therefore, our objective was to assess the effect of sublethal lambda-cyhalothrin exposure on three components of the prey foraging activity (i.e., walking, and prey searching and handling), in both pyrethroid-susceptible and -resistant adults of E. connexa. Both lady beetle populations exhibited similar walking patterns without insecticide exposure in noncontaminated arenas, but in partially contaminated arenas walking differed between strains, such that the resistant insects exhibited greater walking activity. Behavioral avoidance expressed as repellence to lambda-cyhalothrin was not observed for either the susceptible or resistant populations of E. connexa, but the insecticide caused avoidance by means of inducing irritability in 40% of the individuals, irrespective of the strain. Insects remained in the insecticide-contaminated portion of the arena for extended periods resulting in greater exposure. Although lambda-cyhalothrin exposure did not affect prey searching by susceptible lady beetles, prey searching was extended for exposed resistant predators. In contrast, prey handling was not affected by population or by lambda-cyhalothrin exposure. Thus, sublethal exposure to the insecticide in conjunction with the insect resistance profile can affect prey foraging with pyrethroid-exposed resistant predators exhibiting longer prey searching time associated with higher walking activity reducing its predatory performance.

A Preclinical Population Pharmacokinetic Model for Anti‐CD20/CD3 T‐Cell‐Dependent Bispecific Antibodies

PubMed Central

Reyes, Arthur; Sun, Liping L.; Cheu, Melissa; Oldendorp, Amy; Ramanujan, Saroja; Stefanich, Eric G.

2018-01-01

Abstract CD20 is a cell‐surface receptor expressed by healthy and neoplastic B cells and is a well‐established target for biologics used to treat B‐cell malignancies. Pharmacokinetic (PK) and pharmacodynamic (PD) data for the anti‐CD20/CD3 T‐cell‐dependent bispecific antibody BTCT4465A were collected in transgenic mouse and nonhuman primate (NHP) studies. Pronounced nonlinearity in drug elimination was observed in the murine studies, and time‐varying, nonlinear PK was observed in NHPs, where three empirical drug elimination terms were identified using a mixed‐effects modeling approach: i) a constant nonsaturable linear clearance term (7 mL/day/kg); ii) a rapidly decaying time‐varying, linear clearance term (t½ = 1.6 h); and iii) a slowly decaying time‐varying, nonlinear clearance term (t½ = 4.8 days). The two time‐varying drug elimination terms approximately track with time scales of B‐cell depletion and T‐cell migration/expansion within the central blood compartment. The mixed‐effects NHP model was scaled to human and prospective clinical simulations were generated. PMID:29351372

Fear and loathing in the benthos: Responses of aquatic insect larvae to the pesticide imidacloprid in the presence of chemical signals of predation risk.

PubMed

Pestana, João L T; Loureiro, Susana; Baird, Donald J; Soares, Amadeu M V M

2009-06-28

The influence of interactions between pesticide exposure and perceived predation risk on the lethal and sub-lethal responses of two aquatic insects was investigated using the pesticide imidacloprid, and a combination of predator-release kairomones from trout and alarm substances from conspecifics. Laboratory experiments examined feeding and respiration rates of the caddisfly Sericostoma vittatum as well as the growth, emergence and respiration rates of the midge Chironomus riparius, exposed to sub-lethal concentrations of imidacloprid. The effects of the two stressors on burrowing behaviour of both species were also assessed. The results show significant effects of environmentally relevant concentrations of imidacloprid on all endpoints studied. Perceived predation risk also elicited sub-lethal effects in C. riparius and S. vittatum, the latter species being less responsive to predation cues. The effects of simultaneous exposure to both types of stressors were assessed using two different approaches: analysis of variance and conceptual models [concentration addition (CA) and independent action (IA)] normally used for the evaluation of contaminant mixture exposure. Both statistical approaches showed no significant interactions on responses in simultaneous exposures in the majority of parameters assessed with only a signification deviation from the reference CA and IA models being found for C. riparius respiration data contrary to the ANOVA results. Exposure to imidacloprid also compromised antipredator behavioural responses of both insect species, with potential negative consequences in terms of mortality from predation in the field. The results obtained demonstrate that natural and anthropogenic stressors can be treated within the same framework providing compatible data for modelling. For an improved interpretation of ecological effects it will be important to expand the mechanistic study of effects of combined exposure to pesticides and perceived predation risk by measuring different endpoints over a wider range of pesticide concentrations.

Use of sublethal endpoints in sediment toxicity tests with the amphipod Hyalella azteca

USGS Publications Warehouse

Ingersoll, Chris G.; Brunson, Eric L.; Dwyer, F. James; Hardesty, Douglas K.; Kemble, Nile E.

1998-01-01

Short-term sediment toxicity tests that only measure effects on survival can be used to identify high levels of contamination but may not be able to identify marginally contaminated sediments. The objective of the present study was to develop a method for determining the potential sublethal effects of contaminants associated with sediment on the amphipod Hyalella azteca (e.g., reproduction). Exposures to sediment were started with 7- to 8-d-old amphipods. On day 28, amphipods were isolated from the sediment and placed in water-only chambers where reproduction was measured on day 35 and 42. Typically, amphipods were first in amplexus at about day 21 to 28 with release of the first brood between day 28 to 42. Endpoints measured included survival (day 28, 35, and 42), growth (as length and weight on day 28 and 42), and reproduction (number of young/female produced from day 28 to 42). This method was used to evaluate a formulated sediment and field-collected sediments with low to moderate concentrations of contaminants. Survival of amphipods in these sediments was typically >85% after the 28-d sediment exposures and the 14-d holding period in water to measure reproduction. Reproduction was more variable than growth; hence, more replicates might be needed to establish statistical differences among treatments. Previous studies have demonstrated that growth of H. azteca in sediment tests often provides unique information that can be used to discriminate toxic effects of exposure to contaminants. Either length or weight can be measured in sediment tests with H. azteca. However, additional statistical options are available if length is measured on individual amphipods, such as nested analysis of variance that can account for variance in length within replicates. Ongoing water-only studies testing select contaminants will provide additional data on the relative sensitivity and variability of sublethal endpoints in toxicity tests with H. azteca.

The use of growth and behavioral endpoints to assess the effects of pesticide mixtures upon aquatic organisms.

PubMed

Hasenbein, Simone; Lawler, Sharon P; Geist, Juergen; Connon, Richard E

2015-05-01

Aquatic communities are often subject to complex contaminant mixtures, usually at sublethal concentrations, that can cause long-term detrimental effects. Chemicals within mixtures can effectively interact, resulting in synergism, antagonism or additivity. We investigated the tertiary mixture effects of two pyrethroids, lambda-cyhalothrin and permethrin, and the organophosphate chlorpyrifos, evaluating sublethal endpoints; immobility and growth, on Chironomus dilutus in 10-day exposures. We utilized a toxic units (TU) approach, based on median lethal concentrations (LC50) for each compound. The concepts of independent action and concentration addition were used to compare predicted mixture toxicity to observed mixture toxicity. Increased immobility resulted from mixture concentrations ≥1 TU (7.45 ng/L lambda-cyhalothrin × 24.90 ng/L permethrin × 129.70 ng/L chlorpyrifos), and single pesticides concentrations ≥0.25 TU (5.50 ng/L lambda-cyhalothrin, 24.23 ng/L permethrin, 90.92 ng/L chlorpyrifos, respectively). Growth was inhibited by pesticide mixtures ≥0.125 TU (1.04 ng/L lambda-cyhalothrin × 3.15 ng/L permethrin × 15.47 ng/L chlorpyrifos), and singly by lambda-cyhalothrin ≥0.25 TU (5.50 ng/L), and permethrin ≥0.167 TU (18.21 ng/L). The no observed effect concentrations (NOEC) for immobility and growth, for both mixture and single-pyrethroid exposure, were up to 8.0 and 12.0 times respectively lower than the corresponding NOEC for survival. The median effective concentrations (EC50) for growth (mixture and single-pyrethroid exposure) were up to 7.0 times lower than the respective LC50. This study reinforces that the integration of sublethal endpoints in monitoring efforts is powerful in discerning toxic effects that would otherwise be missed by solely utilizing traditional toxicity assessments.

Temperature dependency of the repair of sublethal damage in cultured fish cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitani, H.; Egami, N.

1984-01-01

Established culture fish cells, CAF-MMMI, derived form the goldfish, Carassium auratus, were able to grow and form colonies over a temperature range from 20 to 33/sup 0/ C. While the growth rate of these cells was dependent on incubation temperature, colony formation had no effect on cell survival after ..gamma.. irradiation at high dose rates. The lethal effect of ..gamma.. rays was decreased at low dose rates at 20-33/sup 0/ C, but not at 6/sup 0/ C. Similarly, split-dose experiments showed that recovery from sublethal damage occurred at the higher temperatures, but not at 6/sup 0/ C. These data aremore » consistent with the in vivo data on the effect of temperature on the radiosensitivity and repair of sublethal damage reported previously for live fish.« less

Mesenchymal stem cells from the Wharton’s jelly of umbilical cord segments provide stromal support for the maintenance of cord blood hematopoietic stem cells during long-term ex vivo culture

PubMed Central

Bakhshi, Tiki; Zabriskie, Ryan C.; Bodie, Shamanique; Kidd, Shannon; Ramin, Susan; Paganessi, Laura A.; Gregory, Stephanie A.; Fung, Henry C.; Christopherson, Kent W.

2012-01-01

BACKGROUND Hematopoietic stem cells (HSCs) are routinely obtained from marrow, mobilized peripheral blood, and umbilical cord blood. Mesenchymal stem cells (MSCs) are traditionally isolated from marrow. Bone marrow–derived MSCs (BM-MSCs) have previously demonstrated their ability to act as a feeder layer in support of ex vivo cord blood expansion. However, the use of BM-MSCs to support the growth, differentiation, and engraftment of cord blood may not be ideal for transplant purposes. Therefore, the potential of MSCs from a novel source, the Wharton’s jelly of umbilical cords, to act as stromal support for the long-term culture of cord blood HSC was evaluated. STUDY DESIGN AND METHODS Umbilical cord–derived MSCs (UC-MSCs) were cultured from the Wharton’s jelly of umbilical cord segments. The UC-MSCs were then profiled for expression of 12 cell surface receptors and tested for their ability to support cord blood HSCs in a long-term culture-initiating cell (LTC-IC) assay. RESULTS Upon culture, UC-MSCs express a defined set of cell surface markers (CD29, CD44, CD73, CD90, CD105, CD166, and HLA-A) and lack other markers (CD45, CD34, CD38, CD117, and HLA-DR) similar to BM-MSCs. Like BM-MSCs, UC-MSCs effectively support the growth of CD34+ cord blood cells in LTC-IC assays. CONCLUSION These data suggest the potential therapeutic application of Wharton’s jelly–derived UC-MSCs to provide stromal support structure for the long-term culture of cord blood HSCs as well as the possibility of cotransplantation of genetically identical, HLA-matched, or unmatched cord blood HSCs and UC-MSCs in the setting of HSC transplantation. PMID:18798803

Characterization and functional analyses of a novel chicken CD8a variant X1 (CD8a1)

USDA-ARS?s Scientific Manuscript database

We provide the first description of cloning, as well as structural and functional analysis of a novel variant in the chicken CD8alpha family, termed the CD8-alpha X1 (CD8alpha1) gene. Multiple alignment of CD8alpha1 with known CD8alpha and beta sequences of other species revealed relatively low con...

Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy. INCAS Study Group.

PubMed

Pakker, N G; Kroon, E D; Roos, M T; Otto, S A; Hall, D; Wit, F W; Hamann, D; van der Ende, M E; Claessen, F A; Kauffmann, R H; Koopmans, P P; Kroon, F P; ten Napel, C H; Sprenger, H G; Weigel, H M; Montaner, J S; Lange, J M; Reiss, P; Schellekens, P T; Miedema, F

1999-02-04

Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term. In this study, long-term immune reconstitution was investigated during highly active antiretroviral therapy. Patients enrolled in the INCAS study in The Netherlands were treated for 102 weeks (range 52-144 weeks) with nevirapine (NVP) + zidovudine (ZDV) (n = 9), didanosine (ddl) + ZDV (n = 10), or NVP + ddl + ZDV (n = 10). Memory and naïve CD4+ and CD8+ T cells were measured using CD45RA and CD27 monoclonal antibodies (mAb), T-cell function was assayed by CD3 + CD28 mAb stimulation, and plasma HIV-1 RNA load was measured by ultra-direct assay (cut-off < 20 copies/ml). Compared to both double combination regimens the triple combination regimen resulted in the most sustained increase in CD4+ T cells (change in CD4+, + 253 x 10(6) cells/l; standard error, 79 x 10(6) cells/l) and reduction of plasma HIV-1 RNA. In nine patients (31%) (ddl + ZDV, n = 2; NVP + ddl + ZDV, n = 7) plasma HIV-1 RNA levels remained below cut-off for at least 2 years. On average, these long-term virological responders demonstrated a significantly higher increase of naïve and memory CD4+ T cells (P = 0.01 and 0.02, respectively) as compared with patients with a virological failure, and showed improved T-cell function and normalization of the naïve; memory CD8+ T-cell ratio. However, individual virological success or failure did not predict the degree of immunological response. T-cell patterns were independent of baseline CD4+ T-cell count, T-cell function, HIV-1 RNA load or age. Low numbers of naïve CD4+ T cells at baseline resulted in modest long-term naïve T-cell recovery. Patients with prolonged undetectable plasma HIV-1 RNA levels during antiretroviral therapy do not invariably show immune restoration. Naïve T-cell recovery in the setting of complete viral suppression is a gradual process, similar to that reported for immune recovery in adults after chemotherapy and bone marrow transplantation.

Effects of glyphosate-based herbicides on survival, development and growth of invasive snail (Pomacea canaliculata).

PubMed

Xu, Yanggui; Li, Adela Jing; Li, Kaibin; Qin, Junhao; Li, Huashou

2017-12-01

This study tests the hypotheses that whether environmental relevance of glyphosate would help control spread of the invasive snail Pomacea canaliculata, or benefit its population growth worldwide. Our results showed that glyphosate induced acute toxicity to the snail only at high concentrations (96h LC50 at 175mg/L) unlikely to occur in the environment. Long-term exposures to glyphosate at sublethal levels (20 and 120mg/L) caused inhibition of food intake, limitation of growth performance and alterations in metabolic profiles of the snail. It is worth noting that glyphosate at 2mg/L benefited growth performance in P. canaliculata. Chronic exposures of glyphosate significantly enhanced overall metabolic rate and altered catabolism from protein to carbohydrate/lipid mode. Cellular responses in enzyme activities showed that the exposed snails could increase tolerance by their defense system against glyphosate-induced oxidative stress, and adjustment of metabolism to mitigate energy crisis. Our study displayed that sublethal concentrations of glyphosate might be helpful in control of the invasive species by food intake, growth performance and metabolic interruption; whether environmental relevance of glyphosate (≤2mg/L) benefits population growth of P. canaliculata is still inconclusive, which requires further field study. Copyright © 2017 Elsevier B.V. All rights reserved.

Delayed Hippocampal Effects From a Single Exposure of Prepubertal Guinea Pigs to sub-lethal dose of Chlorpyrifos: A Magnetic Resonance Imaging and Spectroscopy Study

PubMed Central

Mullins, Roger J.; Xu, Su; Pereira, Edna F.R.; Mamczarz, Jacek; Albuquerque, Edson X.; Gullapalli, Rao P.

2013-01-01

This study was designed to test the hypothesis that in vivo Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) can detect in adulthood the neurotoxic effects of a single exposure of prepubertal guinea pigs to the organophosphorus pesticide chlorpyrifos. Twelve female guinea pigs were given either a single dose of chlorpyrifos (0.6xLD50 or 300 mg/kg, sc) or peanut oil (vehicle; 0.5 ml/kg, sc) at 35–40 days of age. One year after the exposure, the animals were tested in the Morris water maze. Three days after the end of the behavioral testing, the metabolic and structural integrity of the brain of the animals was examined by means of MRI/MRS. In the Morris water maze, the chlorpyrifos-exposed guinea pigs showed significant memory deficit. Although no significant anatomical differences were found between the chlorpyrifos-exposed guinea pigs and the control animals by in vivo MRI, the chlorpyrifos-exposed animals showed significant decreases in hippocampal myo-inositol concentration using MRS. The present results indicate that a single sub-lethal exposure of prepubertal guinea pigs to the organophosphorus pesticide chlorpyrifos can lead to long-term memory deficits that are accompanied by significant reductions in the levels of hippocampal myo-inositol. PMID:23411083

Long-term outcomes of children treated for Cushing's disease: a single center experience.

PubMed

Yordanova, Galina; Martin, Lee; Afshar, Farhad; Sabin, Ian; Alusi, Ghassan; Plowman, Nicholas P; Riddoch, Fiona; Evanson, Jane; Matson, Matthew; Grossman, Ashley B; Akker, Scott A; Monson, John P; Drake, William M; Savage, Martin O; Storr, Helen L

2016-12-01

Pediatric Cushing's disease (CD) is rare and there are limited data on the long-term outcomes. We assessed CD recurrence, body composition, pituitary function and psychiatric comorbidity in a cohort of pediatric CD patients. Retrospective review of 21 CD patients, mean age at diagnosis 12.1 years (5.7-17.8), managed in our center between 1986 and 2010. Mean follow-up from definitive treatment was 10.6 years (2.9-27.2). Fifteen patients were in remission following transsphenoidal surgery (TSS) and 5 were in remission following TSS + external pituitary radiotherapy (RT). One patient underwent bilateral adrenalectomy (BA). CD recurrence occurred in 3 (14.3 %) patients: 2 at 2 and 6 years after TSS and 1 7.6 years post-RT. The BA patient developed Nelson's syndrome requiring pituitary RT 0.6 years post-surgery. Short-term growth hormone deficiency (GHD) was present in 14 patients (81 % patients tested) (11 following TSS and 3 after RT) and 4 (44 % of tested) had long-term GHD. Gonadotropin deficiency caused impaired pubertal development in 9 patients (43 %), 4 requiring sex steroid replacement post-puberty. Four patients (19 %) had more than one pituitary hormone deficiency, 3 after TSS and 1 post-RT. Five patients (24 %) had long-term psychiatric co-morbidities (cognitive dysfunction or mood disturbance). There were significant long-term improvements in growth, weight and bone density but not complete reversal to normal in all patients. The long-term consequences of the diagnosis and treatment of CD in children is broadly similar to that seen in adults, with recurrence of CD after successful treatment uncommon but still seen. Pituitary hormone deficiencies occurred in the majority of patients after remission, and assessment and appropriate treatment of GHD is essential. However, while many parameters improve, some children may still have mild but persistent defects.

A BTLA-mediated bait-and-switch strategy permits Listeria expansion in CD8α+ DCs to promote long term T cell responses

PubMed Central

Yang, Xuanming; Zhang, Xunmin; Sun, Yonglian; Tu, Tony; Fu, May Lynne; Miller, Mendy; Fu, Yang-Xin

2014-01-01

SUMMARY Listeria monocytogenes infected CD8α+ DCs in the spleen are essential for CD8+ T cell generation. CD8α+ DCs are also necessary for Listeria expansion and dissemination within the host. The mechanisms that regulate CD8α+ DCs to allow Listeria expansion are unclear. We find that activating the B and T lymphocyte attenuator (BTLA), a co-inhibitory receptor on CD8α+ DCs, suppresses, while blocking BTLA enhances both the primary and memory CD8 T cell responses against Listeria. Btla−/− mice have lower effector and memory CD8+ T cells while paradoxically also being more resistant to Listeria. Although bacterial entry into Btla−/− CD8α+ DCs is unaffected, Listeria fails to expand within these cells. BTLA signaling limits Fas/FasL-mediated suppression of Listeria expansion within CD8α+ DCs to more effectively alert adaptive immune cells. This study uncovers a BTLA-mediated strategy used by the host that permits Listeria proliferation to enable increasing T cell responses for long-term protection. PMID:25011109

Effects of sublethal concentrations of silver nanoparticles on Escherichia coli and Bacillus subtilis under aerobic and anaerobic conditions.

PubMed

Garuglieri, Elisa; Cattò, Cristina; Villa, Federica; Zanchi, Raffaella; Cappitelli, Francesca

2016-12-16

The present work is aimed at comparing the effects of sublethal concentrations of silver nanoparticles (AgNPs) on the growth kinetic, adhesion ability, oxidative stress, and phenotypic changes of model bacteria (Escherichia coli and Bacillus subtilis) under both aerobic and anaerobic conditions. Growth kinetic tests conducted in 96-well microtiter plates revealed that sublethal concentrations of AgNPs do not affect E. coli growth, whereas 1 μg/ml AgNPs increased B. subtilis growth rate under aerobic conditions. At the same concentration, AgNPs promoted B. subtilis adhesion, while it discouraged E. coli attachment to the surface in the presence of oxygen. As determined by 2,7-dichlorofluorescein-diacetate assays, AgNPs increased the formation of intracellular reactive oxygen species, but not at the highest concentrations, suggesting the activation of scavenging systems. Finally, motility assays revealed that 0.01 and 1 μg/ml AgNPs, respectively, promoted surface movement in E. coli and B. subtilis under aerobic and anaerobic conditions. The results demonstrate that E. coli and B. subtilis react differently from AgNPs over a wide range of sublethal concentrations examined under both aerobic and anaerobic conditions. These findings will help elucidate the behavior and impact of engineered nanoparticles on microbial ecosystems.

Chronic Sublethal Effects of Cantharidin on the Diamondback Moth Plutella xylostella (Lepidoptera: Plutellidae).

PubMed

Huang, Zhengyu; Zhang, Yalin

2015-05-29

The diamondback moth, Plutella xylostella (Linnaeus) (Lepidoptera: Plutellidae), is a major pest of cruciferous vegetables worldwide. Cantharidin, a natural toxin isolated from blister beetles, has been reported to be toxic to P. xylostella. However, little is known on the chronic sublethal effects of cantharidin on this species. In this study, we assessed the changes of susceptibility, development, reproduction and other demographic parameters in both the selected P. xylostella strain (Sub, selected by LC25 cantharidin for consecutive 12 generations) and the revertant strain (SubR, derived from the Sub strain without being exposed to cantharidin for 12 generations). Results revealed that the two strains maintained a relatively high-level susceptibility to cantharidin. Severe adverse effects on the population dynamics and fitness in Sub strain were observed. In addition, repeated exposure of P. xylostella to sublethal concentration of cantharidin resulted in negative effects on adult performance and deformities in adults. Although morphologically normal for individuals, the SubR strain exhibited a disadvantage in population growth rate. Our results showed that sublethal concentration of cantharidin exhibited severe negative effects on population growth for longtime. These findings would be useful for assessing the potential effects and risk of cantharidin on P. xylostella and for developing effective integrated pest management.

Synergistic Effect of Combining Plutella xylostella Granulovirus and Bacillus thuringiensis at Sublethal Dosages on Controlling of Diamondback Moth (Lepidoptera: Plutellidae).

PubMed

Han, Guangjie; Li, Chuanming; Liu, Qin; Xu, Jian

2015-10-01

Plutella xylostella granulovirus (PxGV) and Bacillus thuringiensis (Bt) are both entomo-pathogens to the diamondback moth, Plutella xylostella (L.). The purpose of the present study was to measure the effect of the combination of PxGV and Bt at sublethal dosages on the development and mortality of diamondback moth in a laboratory setting. Bt and PxGV exhibited synergistic effect on diamondback moth larval mortality and effectively controlled diamondback moth populations with low dose combination treatment. The combination of three parts per million Bt and 1.3 × 10(3) occlusion bodies per milliliter of PxGV revealed a higher larval mortality compared with the treatment of Bt or PxGV alone. Combination of Bt and PxGV at sublethal concentrations also increased larval duration, reduced oviposition and decreased adult longevity remarkably, resulting in the lowest population trend index among the treatments. The results suggested that the combination of Bt and PxGV at sublethal dosages might provide a valuable way to improve the control efficacy of diamondback moth compared with treatment of Bt or PxGV alone. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Chronic Sublethal Effects of Cantharidin on the Diamondback Moth Plutella xylostella (Lepidoptera: Plutellidae)

PubMed Central

Huang, Zhengyu; Zhang, Yalin

2015-01-01

The diamondback moth, Plutella xylostella (Linnaeus) (Lepidoptera: Plutellidae), is a major pest of cruciferous vegetables worldwide. Cantharidin, a natural toxin isolated from blister beetles, has been reported to be toxic to P. xylostella. However, little is known on the chronic sublethal effects of cantharidin on this species. In this study, we assessed the changes of susceptibility, development, reproduction and other demographic parameters in both the selected P. xylostella strain (Sub, selected by LC25 cantharidin for consecutive 12 generations) and the revertant strain (SubR, derived from the Sub strain without being exposed to cantharidin for 12 generations). Results revealed that the two strains maintained a relatively high-level susceptibility to cantharidin. Severe adverse effects on the population dynamics and fitness in Sub strain were observed. In addition, repeated exposure of P. xylostella to sublethal concentration of cantharidin resulted in negative effects on adult performance and deformities in adults. Although morphologically normal for individuals, the SubR strain exhibited a disadvantage in population growth rate. Our results showed that sublethal concentration of cantharidin exhibited severe negative effects on population growth for longtime. These findings would be useful for assessing the potential effects and risk of cantharidin on P. xylostella and for developing effective integrated pest management. PMID:26035491

Umbilical cord CD71+ erythroid cells are reduced in neonates born to women in spontaneous preterm labor.

PubMed

Gomez-Lopez, Nardhy; Romero, Roberto; Xu, Yi; Miller, Derek; Unkel, Ronald; C MacKenzie, Tippi; Frascoli, Michela; Hassan, Sonia S

2016-10-01

Preterm neonates are highly susceptible to infection. Neonatal host defense against infection seems to be maintained by the temporal presence of immunosuppressive CD71+ erythroid cells. The aim of this study was to investigate whether umbilical cord CD71+ erythroid cells are reduced in neonates born to women who undergo spontaneous preterm labor/birth. Umbilical cord blood samples (n=155) were collected from neonates born to women who delivered preterm with (n=39) and without (n=12) spontaneous labor or at term with (n=82) and without (n=22) spontaneous labor. Time-matched maternal peripheral blood samples were also included (n=111). Mononuclear cells were isolated from these samples, and CD71+ erythroid cells were identified and quantified as CD3-CD235a+CD71+ cells by flow cytometry. (i) The proportion of CD71+ erythroid cells was 50-fold higher in cord blood than in maternal blood; (ii) a reduced number and frequency of umbilical cord CD71+ erythroid cells were found in neonates born to women who underwent spontaneous preterm labor compared to those born to women who delivered preterm without labor; (iii) umbilical cord CD71+ erythroid cells were fewer in neonates born to term pregnancies, regardless of the process of labor, than in those born to women who delivered preterm without labor; and (iv) no differences were seen in umbilical cord CD71+ erythroid cells between neonates born to women who underwent spontaneous preterm labor and those born to women who delivered at term with labor. Umbilical cord CD71+ erythroid cells are reduced in neonates born to women who had undergone spontaneous preterm labor. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Decreased frequency of peripheral CD4(+) CD161(+) Th(17) -precursor cells in kidney transplant recipients on long-term therapy with Belatacept.

PubMed

Vondran, Florian Wolfgang Rudolf; Timrott, Kai; Kollrich, Sonja; Klempnauer, Juergen; Schwinzer, Reinhard; Becker, Thomas

2012-04-01

Clinical trials have pointed out the promising role of co-stimulation blocker Belatacept for improvement of graft function and avoidance of undesired side-effects associated with calcineurin-inhibitors (CNI). However, due to the worldwide limited availability of appropriate patients, almost no data exist to assess the effects of sustained application of this immunomodulator on the recipient's immune system. The aim of this study was to reveal specific alterations in the composition of immunologic subpopulations potentially involved in development of tolerance or chronic graft rejection following long-term Belatacept therapy. For this, peripheral lymphocyte subsets of kidney recipients treated with Belatacept (n=5; average 7.8years) were determined by flow-cytometry and compared with cells from matched patients on CNI (n=9) and healthy controls (n=10). T cells capable of producing IL-17 and serum levels of soluble CD30 were quantified. Patients on CNI showed a higher frequency of CD4(+) CD161(+) Th(17) -precursors and IL-17-producing CD4(+) T cells than Belatacept patients and controls. Significantly higher serum levels of soluble CD30 were observed in CNI patients, indicating a possible involvement of the CD30/CD30L-system in Th(17) -differentiation. No differences were found concerning CD4(+) CD25(+) CD127(low) FoxP3(+) regulatory T cells. In conclusion, patients on therapy with Belatacept did not show a comparable Th(17) -profile to that seen in individuals with chronic intake of CNI. The distinct effects of Belatacept on Th(17) -immunity might prove beneficial for the long-term outcome following kidney transplantation. © 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.

Long-term cadmium exposure influences the abundance of proteins that impact the cell wall structure in medicago sativa stems.

PubMed

Gutsch, Annelie; Keunen, Els; Guerriero, Gea; Renaut, Jenny; Cuypers, Ann; Hausman, Jean-François; Sergeant, Kjell

2018-06-15

Cadmium (Cd) is a non-essential, toxic heavy metal that poses serious threats to both the ecosystem and the health of humans. Plants employ various cellular and molecular mechanisms to minimize the impact of Cd toxicity and the cell walls function as defensive barrier during Cd exposure. In this study, we adopted a quantitative gel-based proteomic approach (two-dimensional difference gel electrophoresis) to investigate changes in the abundance of cell wall- and soluble proteins in stems of Medicago sativa L. upon long-term exposure to Cd (at 10 mg Cd per kg soil as CdSO 4 ). Obtained protein data were complemented with targeted gene expression analyses. Plants were affected by Cd exposure at an early growth stage but seemed to recover at a more mature plant stage as no difference in biomass was observed. The accumulation of Cd was highest in the roots followed by stems and leaves. Quantitative proteomics revealed a changed abundance for 179 cell wall proteins and 30 proteins in the soluble fraction upon long-term Cd exposure. These proteins are involved in cell wall remodeling, defense response, carbohydrate metabolism and promotion of the lignification process. The data indicate that Cd exposure alters the cell wall proteome and underline the role of cell wall proteins in defense against Cd stress. The identified proteins are linked to alterations in the cell wall structure and lignification process in stems of M. sativa, underpinning the function of the cell wall as an effective barrier against Cd stress. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Altered neural processing of emotional faces in remitted Cushing's disease.

PubMed

Bas-Hoogendam, Janna Marie; Andela, Cornelie D; van der Werff, Steven J A; Pannekoek, J Nienke; van Steenbergen, Henk; Meijer, Onno C; van Buchem, Mark A; Rombouts, Serge A R B; van der Mast, Roos C; Biermasz, Nienke R; van der Wee, Nic J A; Pereira, Alberto M

2015-09-01

Patients with long-term remission of Cushing's disease (CD) demonstrate residual psychological complaints. At present, it is not known how previous exposure to hypercortisolism affects psychological functioning in the long-term. Earlier magnetic resonance imaging (MRI) studies demonstrated abnormalities of brain structure and resting-state connectivity in patients with long-term remission of CD, but no data are available on functional alterations in the brain during the performance of emotional or cognitive tasks in these patients. We performed a cross-sectional functional MRI study, investigating brain activation during emotion processing in patients with long-term remission of CD. Processing of emotional faces versus a non-emotional control condition was examined in 21 patients and 21 matched healthy controls. Analyses focused on activation and connectivity of two a priori determined regions of interest: the amygdala and the medial prefrontal-orbitofrontal cortex (mPFC-OFC). We also assessed psychological functioning, cognitive failure, and clinical disease severity. Patients showed less mPFC activation during processing of emotional faces compared to controls, whereas no differences were found in amygdala activation. An exploratory psychophysiological interaction analysis demonstrated decreased functional coupling between the ventromedial PFC and posterior cingulate cortex (a region structurally connected to the PFC) in CD-patients. The present study is the first to show alterations in brain function and task-related functional coupling in patients with long-term remission of CD relative to matched healthy controls. These alterations may, together with abnormalities in brain structure, be related to the persisting psychological morbidity in patients with CD after long-term remission. Copyright © 2015 Elsevier Ltd. All rights reserved.

Glioblastoma-targeted CD4+ CAR T cells mediate superior antitumor activity.

PubMed

Wang, Dongrui; Aguilar, Brenda; Starr, Renate; Alizadeh, Darya; Brito, Alfonso; Sarkissian, Aniee; Ostberg, Julie R; Forman, Stephen J; Brown, Christine E

2018-05-17

Chimeric antigen receptor-modified (CAR-modified) T cells have shown promising therapeutic effects for hematological malignancies, yet limited and inconsistent efficacy against solid tumors. The refinement of CAR therapy requires an understanding of the optimal characteristics of the cellular products, including the appropriate composition of CD4+ and CD8+ subsets. Here, we investigated the differential antitumor effect of CD4+ and CD8+ CAR T cells targeting glioblastoma-associated (GBM-associated) antigen IL-13 receptor α2 (IL13Rα2). Upon stimulation with IL13Rα2+ GBM cells, the CD8+ CAR T cells exhibited robust short-term effector function but became rapidly exhausted. By comparison, the CD4+ CAR T cells persisted after tumor challenge and sustained their effector potency. Mixing with CD4+ CAR T cells failed to ameliorate the effector dysfunction of CD8+ CAR T cells, while surprisingly, CD4+ CAR T cell effector potency was impaired when coapplied with CD8+ T cells. In orthotopic GBM models, CD4+ outperformed CD8+ CAR T cells, especially for long-term antitumor response. Further, maintenance of the CD4+ subset was positively correlated with the recursive killing ability of CAR T cell products derived from GBM patients. These findings identify CD4+ CAR T cells as a highly potent and clinically important T cell subset for effective CAR therapy.

Glioblastoma-targeted CD4+ CAR T cells mediate superior antitumor activity

PubMed Central

Wang, Dongrui; Starr, Renate; Alizadeh, Darya; Brito, Alfonso; Sarkissian, Aniee; Ostberg, Julie R.; Forman, Stephen J.; Brown, Christine E.

2018-01-01

Chimeric antigen receptor–modified (CAR-modified) T cells have shown promising therapeutic effects for hematological malignancies, yet limited and inconsistent efficacy against solid tumors. The refinement of CAR therapy requires an understanding of the optimal characteristics of the cellular products, including the appropriate composition of CD4+ and CD8+ subsets. Here, we investigated the differential antitumor effect of CD4+ and CD8+ CAR T cells targeting glioblastoma-associated (GBM-associated) antigen IL-13 receptor α2 (IL13Rα2). Upon stimulation with IL13Rα2+ GBM cells, the CD8+ CAR T cells exhibited robust short-term effector function but became rapidly exhausted. By comparison, the CD4+ CAR T cells persisted after tumor challenge and sustained their effector potency. Mixing with CD4+ CAR T cells failed to ameliorate the effector dysfunction of CD8+ CAR T cells, while surprisingly, CD4+ CAR T cell effector potency was impaired when coapplied with CD8+ T cells. In orthotopic GBM models, CD4+ outperformed CD8+ CAR T cells, especially for long-term antitumor response. Further, maintenance of the CD4+ subset was positively correlated with the recursive killing ability of CAR T cell products derived from GBM patients. These findings identify CD4+ CAR T cells as a highly potent and clinically important T cell subset for effective CAR therapy. PMID:29769444

Long-term protection against SHIV89.6P replication in HIV-1 Tat vaccinated cynomolgus monkeys.

PubMed

Maggiorella, Maria Teresa; Baroncelli, Silvia; Michelini, Zuleika; Fanales-Belasio, Emanuele; Moretti, Sonia; Sernicola, Leonardo; Cara, Andrea; Negri, Donatella R M; Buttò, Stefano; Fiorelli, Valeria; Tripiciano, Antonella; Scoglio, Arianna; Caputo, Antonella; Borsetti, Alessandra; Ridolfi, Barbara; Bona, Roberta; ten Haaft, Peter; Macchia, Iole; Leone, Pasqualina; Pavone-Cossut, Maria Rosaria; Nappi, Filomena; Ciccozzi, Massimo; Heeney, Jonathan; Titti, Fausto; Cafaro, Aurelio; Ensoli, Barbara

2004-09-03

Vaccination with a biologically active Tat protein or tat DNA contained infection with the highly pathogenic SHIV89.6P virus, preventing CD4 T-cell decline and disease onset. Here we show that protection was prolonged, since neither CD4 T-cell decline nor active virus replication was observed in all vaccinated animals that controlled virus replication up to week 104 after the challenge. In contrast, virus persisted and replicated in peripheral blood mononuclear cells and lymph nodes of infected animals, two of which died. Tat-specific antibody, CD4 and CD8 T-cell responses were high and stable only in the animals controlling the infection. In contrast, Gag-specific antibody production and CD4 and CD8 T-cell responses were consistently and persistently positive only in the monkeys that did not control primary virus replication. These results indicate that vaccination with Tat protein or DNA induced long-term memory Tat-specific immune responses and controlled primary infection at its early stages allowing a long-term containment of virus replication and spread in blood and tissues.

A MECHANISM OF THE GLYCOGENOLYTIC ACTION OF BACTERIAL ENDOTOXIN

PubMed Central

Sanford, Jay P.; Barnett, Jack A.; Gott, Cora

1960-01-01

These experiments have demonstrated that liver glycogen may rise or fall after endotoxin administration, depending upon the antecedent diet and that total adrenalectomy followed by corticosteroid replacement abolishes the glycogenolytic effect of sublethal doses of endotoxin. It is concluded that the derangements of carbohydrate metabolism observed following the administration of sublethal quantities of bacterial endotoxin represent, not a direct hepatotoxic effect of endotoxin, but rather the passive consequence of epinephrine release. PMID:13746229

Sublethal pesticide doses negatively affect survival and the cellular responses in American foulbrood-infected honeybee larvae

NASA Astrophysics Data System (ADS)

López, Javier Hernández; Krainer, Sophie; Engert, Antonia; Schuehly, Wolfgang; Riessberger-Gallé, Ulrike; Crailsheim, Karl

2017-02-01

Disclosing interactions between pesticides and bee infections is of most interest to understand challenges that pollinators are facing and to which extent bee health is compromised. Here, we address the individual and combined effect that three different pesticides (dimethoate, clothianidin and fluvalinate) and an American foulbrood (AFB) infection have on mortality and the cellular immune response of honeybee larvae. We demonstrate for the first time a synergistic interaction when larvae are exposed to sublethal doses of dimethoate or clothianidin in combination with Paenibacillus larvae, the causative agent of AFB. A significantly higher mortality than the expected sum of the effects of each individual stressor was observed in co-exposed larvae, which was in parallel with a drastic reduction of the total and differential hemocyte counts. Our results underline that characterizing the cellular response of larvae to individual and combined stressors allows unmasking previously undetected sublethal effects of pesticides in colony health.

Effects of sublethal exposure to boric acid sugar bait on adult survival, host-seeking, bloodfeeding behavior, and reproduction of Stegomyia albopicta.

PubMed

Ali, Arshad; Xue, Rui-De; Barnard, Donald R

2006-09-01

Effects of sublethal exposure to 0.1% boric acid sugar bait on adult survival, host-seeking, bloodfeeding behavior, and reproduction of Stegomyia albopicta were studied in the laboratory. Survival of males as well as females was significantly reduced when exposed to the bait, compared to control adults. The host-seeking and bloodfeeding activities in the baited females decreased, but the mean duration of blood engorgement (probing to voluntary withdrawal of proboscis) was not significantly different between the baited and control females. The landing and biting rates (human forearm) were significantly reduced in the baited females compared to nonbaited controls. Fecundity and fertility (based on number of laid eggs per female and percentage egg hatch, respectively) in the baited females were significantly reduced, and ovarian development was retarded. Sublethal exposure to sugar-based boric acid bait has the potential to reduce adult populations of St. albopicta.

Pesticide risk assessment in free-ranging bees is weather and landscape dependent.

PubMed

Henry, Mickaël; Bertrand, Colette; Le Féon, Violette; Requier, Fabrice; Odoux, Jean-François; Aupinel, Pierrick; Bretagnolle, Vincent; Decourtye, Axel

2014-07-10

The risk assessment of plant protection products on pollinators is currently based on the evaluation of lethal doses through repeatable lethal toxicity laboratory trials. Recent advances in honeybee toxicology have, however, raised interest on assessing sublethal effects in free-ranging individuals. Here, we show that the sublethal effects of a neonicotinoid pesticide are modified in magnitude by environmental interactions specific to the landscape and time of exposure events. Field sublethal assessment is therefore context dependent and should be addressed in a temporally and spatially explicit way, especially regarding weather and landscape physiognomy. We further develop an analytical Effective Dose (ED) framework to help disentangle context-induced from treatment-induced effects and thus to alleviate uncertainty in field studies. Although the ED framework involves trials at concentrations above the expected field exposure levels, it allows to explicitly delineating the climatic and landscape contexts that should be targeted for in-depth higher tier risk assessment.

Evaluation of sublethal effects of polymer-based essential oils nanoformulation on the german cockroach.

PubMed

González, Jorge Werdin; Yeguerman, Cristhian; Marcovecchio, Diego; Delrieux, Claudio; Ferrero, Adriana; Band, Beatriz Fernández

2016-08-01

The German cockroach, Blattella germanica (L.), is a serious household and public health pest worldwide. The aim of the present study was to evaluate the sublethal activity of polymer-based essential oils (EOs) nanoparticles (NPs) on adults of B. germanica. The LC50 and LC25 for contact toxicity were determined. To evaluate the repellency of EOs and NPs at LC25, a software was specially created in order to track multiple insects on just-recorded videos, and generate statistics using the obtained information. The effects of EOs and NPs at LC25 and LC50 on the nutritional physiology were also evaluated. The results showed that NPs exerted sublethal effects on the German cockroach, since these products enhance the repellent effects of the EOs and negatively affected the nutritional indices and the feeding deterrence index. Copyright © 2016 Elsevier Inc. All rights reserved.

Sublethal pesticide doses negatively affect survival and the cellular responses in American foulbrood-infected honeybee larvae.

PubMed

López, Javier Hernández; Krainer, Sophie; Engert, Antonia; Schuehly, Wolfgang; Riessberger-Gallé, Ulrike; Crailsheim, Karl

2017-02-01

Disclosing interactions between pesticides and bee infections is of most interest to understand challenges that pollinators are facing and to which extent bee health is compromised. Here, we address the individual and combined effect that three different pesticides (dimethoate, clothianidin and fluvalinate) and an American foulbrood (AFB) infection have on mortality and the cellular immune response of honeybee larvae. We demonstrate for the first time a synergistic interaction when larvae are exposed to sublethal doses of dimethoate or clothianidin in combination with Paenibacillus larvae, the causative agent of AFB. A significantly higher mortality than the expected sum of the effects of each individual stressor was observed in co-exposed larvae, which was in parallel with a drastic reduction of the total and differential hemocyte counts. Our results underline that characterizing the cellular response of larvae to individual and combined stressors allows unmasking previously undetected sublethal effects of pesticides in colony health.

Sublethal Lead Exposure Alters Movement Behavior in Free-Ranging Golden Eagles.

PubMed

Ecke, Frauke; Singh, Navinder J; Arnemo, Jon M; Bignert, Anders; Helander, Björn; Berglund, Åsa M M; Borg, Hans; Bröjer, Caroline; Holm, Karin; Lanzone, Michael; Miller, Tricia; Nordström, Åke; Räikkönen, Jannikke; Rodushkin, Ilia; Ågren, Erik; Hörnfeldt, Birger

2017-05-16

Lead poisoning of animals due to ingestion of fragments from lead-based ammunition in carcasses and offal of shot wildlife is acknowledged globally and raises great concerns about potential behavioral effects leading to increased mortality risks. Lead levels in blood were correlated with progress of the moose hunting season. Based on analyses of tracking data, we found that even sublethal lead concentrations in blood (25 ppb, wet weight), can likely negatively affect movement behavior (flight height and movement rate) of free-ranging scavenging Golden Eagles (Aquila chrysaetos). Lead levels in liver of recovered post-mortem analyzed eagles suggested that sublethal exposure increases the risk of mortality in eagles. Such adverse effects on animals are probably common worldwide and across species, where game hunting with lead-based ammunition is widespread. Our study highlights lead exposure as a considerably more serious threat to wildlife conservation than previously realized and suggests implementation of bans of lead ammunition for hunting.

Impact of imidacloprid on new queens of imported fire ants, Solenopsis invicta (Hymenoptera: Formicidae)

PubMed Central

Wang, Lei; Zeng, Ling; Chen, Jian

2015-01-01

Neonicotinoid insecticides are commonly used in managing pest insects, including the imported fire ant, Solenopsis invicta Buren. There is increasing evidence that neonicotinoid insecticides at sublethal concentrations have profound effects on social insects. However, the sublethal effect of neonicotinoids on S. invicta has never been investigated. In this study, the newly mated queens were fed with water containing 0.01 or 0.25 μg/ml imidacloprid. Imidacloprid at both concentrations did not cause any increase in queen mortality during the founding stage; however, it significantly reduced queens’ brood tending ability. In the 0.25 μg/ml imidacloprid treatment, the time to larval emergence was significantly delayed and no pupae or adult workers were produced. This study provides clear evidence that imidacloprid at sublethal concentrations has a significant detrimental impact on S. invicta queens and the development of incipient colonies. PMID:26643971

A Preclinical Population Pharmacokinetic Model for Anti-CD20/CD3 T-Cell-Dependent Bispecific Antibodies.

PubMed

Ferl, Gregory Z; Reyes, Arthur; Sun, Liping L; Cheu, Melissa; Oldendorp, Amy; Ramanujan, Saroja; Stefanich, Eric G

2018-05-01

CD20 is a cell-surface receptor expressed by healthy and neoplastic B cells and is a well-established target for biologics used to treat B-cell malignancies. Pharmacokinetic (PK) and pharmacodynamic (PD) data for the anti-CD20/CD3 T-cell-dependent bispecific antibody BTCT4465A were collected in transgenic mouse and nonhuman primate (NHP) studies. Pronounced nonlinearity in drug elimination was observed in the murine studies, and time-varying, nonlinear PK was observed in NHPs, where three empirical drug elimination terms were identified using a mixed-effects modeling approach: i) a constant nonsaturable linear clearance term (7 mL/day/kg); ii) a rapidly decaying time-varying, linear clearance term (t ½  = 1.6 h); and iii) a slowly decaying time-varying, nonlinear clearance term (t ½  = 4.8 days). The two time-varying drug elimination terms approximately track with time scales of B-cell depletion and T-cell migration/expansion within the central blood compartment. The mixed-effects NHP model was scaled to human and prospective clinical simulations were generated. © 2018 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Relationship of long-term highly active antiretroviral therapy on salivary flow rate and CD4 Count among HIV-infected patients.

PubMed

Kumar, J Vijay; Baghirath, P Venkat; Naishadham, P Parameswar; Suneetha, Sujai; Suneetha, Lavanya; Sreedevi, P

2015-01-01

To determine if long-term highly active antiretroviral therapy (HAART) therapy alters salivary flow rate and also to compare its relation of CD4 count with unstimulated and stimulated whole saliva. A cross-sectional study was performed on 150 individuals divided into three groups. Group I (50 human immunodeficiency virus (HIV) seropositive patients, but not on HAART therapy), Group II (50 HIV-infected subjects and on HAART for less than 3 years called short-term HAART), Group III (50 HIV-infected subjects and on HAART for more than or equal to 3 years called long-term HAART). Spitting method proposed by Navazesh and Kumar was used for the measurement of unstimulated and stimulated salivary flow rate. Chi-square test and analysis of variance (ANOVA) were used for statistical analysis. The mean CD4 count was 424.78 ± 187.03, 497.82 ± 206.11 and 537.6 ± 264.00 in the respective groups. Majority of the patients in all the groups had a CD4 count between 401 and 600. Both unstimulated and stimulated whole salivary (UWS and SWS) flow rates in Group I was found to be significantly higher than in Group II (P < 0.05). Unstimulated salivary flow rate between Group II and III subjects were also found to be statistically significant (P < 0.05). ANOVA performed between CD4 count and unstimulated and stimulated whole saliva in each group demonstrated a statistically significant relationship in Group II (P < 0.05). There were no significant results found between CD4 count and stimulated whole saliva in each groups. The reduction in CD4 cell counts were significantly associated with salivary flow rates of HIV-infected individuals who are on long-term HAART.

[Relationship among the Oxygen Concentration, Reactive Oxygen Species and the Biological Characteristics of Mouse Bone Marrow Hematopoietic Stem Cells].

PubMed

Ren, Si-Hua; He, Yu-Xin; Ma, Yi-Ran; Jin, Jing-Chun; Kang, Dan

2016-02-01

To investigate the effects of oxygen concentration and reactive oxygen species (ROS) on the biological characteristics of hematopoietic stem cells (HSC) and to analyzed the relationship among the oxygen concentration, ROS and the biological characteristics of mouse HSC through simulation of oxygen environment experienced by PB HSC during transplantation. The detection of reactive oxygen species (ROS), in vitro amplification, directional differentiation (BFU-E, CFU-GM, CFU-Mix), homing of adhesion molecules (CXCR4, CD44, VLA4, VLA5, P-selectin), migration rate, CFU-S of NOD/SCID mice irradiated with sublethal dose were performed to study the effect of oxgen concentration and reactive oxygen species on the biological characteristics of mouse BM-HSC and the relationship among them. The oxygen concentrations lower than normal oxygen concentration (especially hypoxic oxygen environment) could reduce ROS level and amplify more Lin(-) c-kit(+) Sca-1(+) BM HSC, which was more helpful to the growth of various colonies (BFU-E, CFU-GM, CFU-Mix) and to maintain the migratory ability of HSC, thus promoting CFU-S growth significantly after the transplantation of HSC in NOD/SCID mice irradiated by a sublethal dose. BM HSC exposed to oxygen environments of normal, inconstant oxygen level and strenuously thanging of oxygen concentration could result in higher level of ROS, at the same time, the above-mentioned features and functional indicators were relatively lower. The ROS levels of BM HSC in PB HSCT are closely related to the concentrations and stability of oxygen surrounding the cells. High oxygen concentration results in an high level of ROS, which is not helpful to maintain the biological characteristics of BM HSC. Before transplantation and in vitro amplification, the application of antioxidancs and constant oxygen level environments may be beneficial for transplantation of BMMSC.

Intersex and liver alterations induced by long-term sublethal exposure to 17α-ethinylestradiol in adult male Cnesterodon decemmaculatus (Pisces: Poeciliidae).

PubMed

Young, Brian Jonathan; López, Gabriela Carina; Cristos, Diego Sebastián; Crespo, Diana Cristina; Somoza, Gustavo Manuel; Carriquiriborde, Pedro

2017-07-01

The aim of the present study was to assess the responses of the gonopodium morphology and the gonadal and liver histology of adult male Cnesterodon decemmaculatus to sublethal long-term exposure concentrations of 17α-ethinylestradiol (EE2). Two experiments were conducted exposing the fish to waterborne concentrations of EE2 ranging from 20 ng/L to 200 ng/L for 8 wk, 12 wk, and 16 wk. Intersex gonads were observed after 8 wk and 16 wk in fish exposed to 200 ng EE2/L and 100 ng EE2/L, respectively. Oocytes' development from testis germ cells and replacement of the efferent duct periodic acid-Schiff-positive secretion surrounding spermatozeugmata by parenchymal tissue and duct structure alterations were the major observed changes in the gonads. In contrast, no response was observed in the gonopodium morphology. Liver histology was also altered, showing increasing steatosis, single-cell necrosis to generalized necrosis, and disruption of acinar organization from 100 ng EE2/L to 200 ng EE2/L. In summary, the present results showed that although EE2 was not able to alter the morphology of a developed gonopodium, it was capable of inducing development of testicular oocytes in adult male C. decemmaculatus at environmentally relevant concentrations. Thus, externally normal but intersex C. decemmaculatus males would be expected in the wastewater-receiving streams that the species inhabits. According to the literature, the present study would be the first indicating estrogen-induced intersex in adult male poeciliid. Environ Toxicol Chem 2017;36:1738-1745. © 2016 SETAC. © 2016 SETAC.

Selective CD28 Antagonist Blunts Memory Immune Responses and Promotes Long-Term Control of Skin Inflammation in Nonhuman Primates.

PubMed

Poirier, Nicolas; Chevalier, Melanie; Mary, Caroline; Hervouet, Jeremy; Minault, David; Baker, Paul; Ville, Simon; Le Bas-Bernardet, Stephanie; Dilek, Nahzli; Belarif, Lyssia; Cassagnau, Elisabeth; Scobie, Linda; Blancho, Gilles; Vanhove, Bernard

2016-01-01

Novel therapies that specifically target activation and expansion of pathogenic immune cell subsets responsible for autoimmune attacks are needed to confer long-term remission. Pathogenic cells in autoimmunity include memory T lymphocytes that are long-lived and present rapid recall effector functions with reduced activation requirements. Whereas the CD28 costimulation pathway predominantly controls priming of naive T cells and hence generation of adaptive memory cells, the roles of CD28 costimulation on established memory T lymphocytes and the recall of memory responses remain controversial. In contrast to CD80/86 antagonists (CTLA4-Ig), selective CD28 antagonists blunt T cell costimulation while sparing CTLA-4 and PD-L1-dependent coinhibitory signals. Using a new selective CD28 antagonist, we showed that Ag-specific reactivation of human memory T lymphocytes was prevented. Selective CD28 blockade controlled both cellular and humoral memory recall in nonhuman primates and induced long-term Ag-specific unresponsiveness in a memory T cell-mediated inflammatory skin model. No modification of memory T lymphocytes subsets or numbers was observed in the periphery, and importantly no significant reactivation of quiescent viruses was noticed. These findings indicate that pathogenic memory T cell responses are controlled by both CD28 and CTLA-4/PD-L1 cosignals in vivo and that selectively targeting CD28 would help to promote remission of autoimmune diseases and control chronic inflammation. Copyright © 2015 by The American Association of Immunologists, Inc.

Release from quiescence of CD34+ CD38- human umbilical cord blood cells reveals their potentiality to engraft adults.

PubMed Central

Cardoso, A A; Li, M L; Batard, P; Hatzfeld, A; Brown, E L; Levesque, J P; Sookdeo, H; Panterne, B; Sansilvestri, P; Clark, S C

1993-01-01

Using optimal culture conditions in which the transforming growth factor beta 1 (TGF-beta 1) inhibitory loop has been interrupted by antisense TGF-beta 1 oligonucleotides or anti-TGF-beta serum, we have compared the proliferative capacities and the abilities of the CD34+ CD38- cell populations from bone marrow and umbilical cord blood to generate early progenitors in long-term cultures. The CD34+ CD38- fraction of umbilical cord blood accounts for 4% of the CD34+ fraction compared to only 1% in bone marrow, indicating that umbilical cord blood may be relatively enriched in stem cells. We estimate that the CD34+ CD38- cells from a typical umbilical cord blood sample produce equivalent numbers of colony-forming units (CFU)-granulocyte/erythrocyte/macrophage/megakaryocyte, twice as many CFU-granulocyte/macrophage (GM) and 3 times as many burst-forming units-erythroid as the same population from an average bone marrow sample used in adult transplantation. In addition, the colonies resulting from the umbilical cord blood samples were significantly larger than those from bone marrow, indicating a greater growth potential. However, the content of later progenitors, which may be important for short-term reconstitution, was less in umbilical cord blood-derived than in bone marrow-derived cell preparations, as estimated by a 4-fold lower production of CFU-GM in long-term cultures of CD34+ CD38+ cells. This deficit is partially compensated by the higher growth capacity of the resulting CFU-GM. These studies suggest that umbilical cord blood is a suitable source of cells for adult transplantation. PMID:7690969

Long-term parenteral administration of 2-hydroxypropyl-β-cyclodextrin causes bone loss.

PubMed

Kantner, Ingrid; Erben, Reinhold G

2012-07-01

Cyclodextrins are oligosaccharides which are used in the pharmaceutical industry and research as vehicles for application of apolar substances such as steroids. The aim of this study was to examine the long-term effects of parenteral administration of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) on bone. Sham-operated (SHAM) or ovariectomized (OVX) adult rats were subcutaneously injected with physiological saline, 50, or 200 mg/kg HP-β-CD daily. After 4 months, body weight in OVX rats and uterine weight in SHAM rats were significantly lower after administration of 200 mg/kg HP-β-CD, relative to vehicle controls. At 200 mg/kg, HP-β-CD was hepatotoxic as measured by increased serum transaminases, and reduced serum albumin. Moreover, 200 mg/kg HP-β-CD led to decreased vertebral and tibial bone mineral density (BMD), and to cortical thinning at the tibial shaft. Bone loss in HP-β-CD-treated rats was associated with increased bone resorption as measured by increased renal deoxypyridinoline excretion. Although 50 mg/kg HP-β-CD was devoid of overt signs of organ toxicity and did not impair BMD, bone resorption was already increased. In summary, subcutaneous long-term administration of HP-β-CD at a daily dose of 200 mg/kg led to increased bone resorption and subsequent bone loss. Minor alterations in bone metabolism were also seen at 50 mg/kg.

Influence of modified atmospheric storage, lactic acid, and NaCl on survival of sublethally heat-injured Listeria monocytogenes.

PubMed

Williams, R C; Golden, D A

2001-03-20

The effect of package atmosphere on survival of uninjured and sublethally heat-injured Listeria monocytogenes, inoculated onto tryptose phosphate agar containing 0.85% lactic acid and 2% NaCl (TPALAS) was investigated. Inoculated TPALAS plates were packaged in air, 100% N2 (N2), 30% CO2-70% N2 (CO2-N2), and vacuum and stored at 4 and 20 degrees C for up to 31 days. Recovery of L. monocytogenes from TPALAS was influenced by the injury status (i.e., injured and uninjured) of the inoculum, storage atmosphere (air, N2, CO2-N2, and vacuum), storage temperature (4 and 20 degrees C), and recovery media [tryptose phosphate agar (TPA) and modified Oxford agar (MOX)] (P <0.05). Overall, storage at 4 degrees C supported greater survival than storage at 20 degrees C (P< 0.05). Uninjured L. monocytogenes stored at 4 degrees C was recovered on TPA better than sublethally heat-injured L. monocytogenes stored at 40 degrees C (P < 0.05). Recovery of sublethally heat-injured L. monocytogenes stored at 4 degrees C followed the order N2 > CO2-N2 > air > vacuum (P < 0.05), whereas recovery of uninjured L. monocyrogenes stored at 4 degrees C followed the order N2 > CO2-N2 > vacuum > air (P < 0.05). Air and vacuum atmospheres supported greater survival of uninjured and heat-injured L. monocytogenes than N2 and CO2-N2 atmospheres at 20 degrees C (P < 0.05). Recovery of sublethally heat-injured L. monocytogenes stored at 20 degrees C followed the order vacuum > air> CO2-N2 = N2 (P <0.05), whereas recovery of uninjured L. monocytogenes stored at 20 degrees C followed the order vacuum > air> CO2-N2 > N2 (P<0.05). Uninjured L. monocytogenes stored under N2 at 4 degrees C was recovered best, whereas sublethally heat-injured L. monocytogenes stored under N2 at 20 degrees C was recovered poorest (P < 0.05). Factors such as package atmosphere and storage temperature, involved in the production, storage, and distribution of fermented foods must be thoroughly evaluated when determining strategies for control and detection of L. monocytogenes in such products.

Lethal and sublethal effects of azadirachtin on the bumblebee Bombus terrestris (Hymenoptera: Apidae).

PubMed

Barbosa, Wagner Faria; De Meyer, Laurens; Guedes, Raul Narciso C; Smagghe, Guy

2015-01-01

Azadirachtin is a biorational insecticide commonly reported as selective to a range of beneficial insects. Nonetheless, only few studies have been carried out with pollinators, usually emphasizing the honeybee Apis mellifera and neglecting other important pollinator species such as the bumblebee Bombus terrestris. Here, lethal and sublethal effects of azadirachtin were studied on B. terrestris via oral exposure in the laboratory to bring out the potential risks of the compound to this important pollinator. The compound was tested at different concentrations above and below the maximum concentration that is used in the field (32 mg L(-1)). As most important results, azadirachtin repelled bumblebee workers in a concentration-dependent manner. The median repellence concentration (RC50) was estimated as 504 mg L(-1). Microcolonies chronically exposed to azadirachtin via treated sugar water during 11 weeks in the laboratory exhibited a high mortality ranging from 32 to 100 % with a range of concentrations between 3.2 and 320 mg L(-1). Moreover, no reproduction was scored when concentrations were higher than 3.2 mg L(-1). At 3.2 mg L(-1), azadirachtin significantly inhibited the egg-laying and, consequently, the production of drones during 6 weeks. Ovarian length decreased with the increase of the azadirachtin concentration. When azadirachtin was tested under an experimental setup in the laboratory where bumblebees need to forage for food, the sublethal effects were stronger as the numbers of drones were reduced already with a concentration of 0.64 mg L(-1). Besides, a negative correlation was found between the body mass of male offspring and azadirachtin concentration. In conclusion, our results as performed in the laboratory demonstrated that azadirachtin can affect B. terrestris with a range of sublethal effects. Taking into account that sublethal effects are as important as lethal effects for the development and survival of the colonies of B. terrestris, this study confirms the need to test compounds on their safety, especially when they have to perform complex tasks such as foraging. The latter agrees with the recent European Food Safety Authority guidelines to assess 'potentially deleterious' compounds for sublethal effects on behavior.

Changes in cosmonauts' innate immunity after the long-term space flights

NASA Astrophysics Data System (ADS)

Ponomarev, Sergey; Rykova, Marina; Boris, Morukov; Berendeeva, Tatiana; Antropova, Evgeniya

It’s well known that the immune system is exposed to adverse influence during the space flight. For the purpose of finding out the character of similar changes in innate immunity using the flow cytometry research was spent an estimation of some key parameters characterizing a condition of natural resistance system of 8 cosmonauts before and after the long-term space flights, such as expression of Toll-like receptors (TLR2, TLR4, TLR6), adhesion molecules (CD54, CD24, CD11b, CD18), an Fc-receptor (CD16), a scavenger-receptor (CD36), a mannose receptor (CD206. Furthermore using enzyme-linked immunosorbent assay the level of the main TLR4 and TLR6 ligand - heat-shock protein 70 (HSP70) was explored. Also we defined the level of cytokine production after the lipopolysaccharide (LPS) monocyte activation in vitro. The study was conducted for 60 days before the flight, as well as at 1 and 7 days after the completion of the space missions. We found no reliable changes in the content of monocytes expressing on their surface in CD54, CD24, CD11b, CD18, CD1 and CD206. But the level of TLR2+, TLR4+, TLR6+ monocytes in all 8 cosmonauts was significantly increased on the 1 day after landing compared with the baseline values. At the same time we saw the significant increase of HSP70 in the cosmonauts’ serum on the 1 day after landing compared also with the baseline values. In spite of the increased TLR4+ monocyte level on the 1 day after landing, the LPS-induced cytokine production in the same period in cell cultures in vitro was lower than before flights. Moreover, this negative trend persisted at 7 day after the completion of long-term space missions. Such a dynamics can reflect an exhaustion of innate immunity reserve possibilities which in turn may lead to increase the infection and autoimmune diseases.

Long-term patterns in CD4 response are determined by an interaction between baseline CD4 cell count, viral load, and time: The Asia Pacific HIV Observational Database (APHOD).

PubMed

Egger, Sam; Petoumenos, Kathy; Kamarulzaman, Adeeba; Hoy, Jennifer; Sungkanuparph, Somnuek; Chuah, John; Falster, Kathleen; Zhou, Jialun; Law, Matthew G

2009-04-15

Random effects models were used to explore how the shape of CD4 cell count responses after commencing combination antiretroviral therapy (cART) develop over time and, in particular, the role of baseline and follow-up covariates. Patients in Asia Pacific HIV Observational Database who first commenced cART after January 1, 1997, and who had a baseline CD4 cell count and viral load measure and at least 1 follow-up measure between 6 and 24 months, were included. CD4 cell counts were determined at every 6-month period after the commencement of cART for up to 6 years. A total of 1638 patients fulfilled the inclusion criteria with a median follow-up time of 58 months. Lower post-cART mean CD4 cell counts were found to be associated with increasing age (P < 0.001), pre-cART hepatitis C coinfection (P = 0.038), prior AIDS (P = 0.019), baseline viral load < or equal to 100,000 copies per milliliter (P < 0.001), and the Asia Pacific region compared with Australia (P = 0.005). A highly significant 3-way interaction between the effects of time, baseline CD4 cell count, and post-cART viral burden (P < 0.0001) was demonstrated. Higher long-term mean CD4 cell counts were associated with lower baseline CD4 cell count and consistently undetectable viral loads. Among patients with consistently detectable viral load, CD4 cell counts seemed to converge for all baseline CD4 levels. Our analysis suggest that the long-term shape of post-cART CD4 cell count changes depends only on a 3-way interaction between baseline CD4 cell count, viral load response, and time.

Neuropathological Consequences of Exposure to Sublethal Doses of Cyanide

DTIC Science & Technology

1992-11-01

identify by block number) Experiments focused on the effects of cyanide on brain energy metabolism , microdialysis studies (to measure acid products of...Discussion 15 Brain metabolism studies 15 Table L Effect of cyanide on local cerebral glucose 17 use (pmol/lO0 glmin). Microdialysis studies 18 Figure 2. Local...Brain metabolism studies: To determine the brain regions affected by sublethal doses of cyanide, male rats were given saline or NaCN by controlled iv

The Effect of Acclimation to Sublethal Temperature on Subsequent Susceptibility of Sitophilus zeamais Mostchulsky (Coleoptera: Curculionidae) to High Temperatures

PubMed Central

Lü, Jianhua; Zhang, Huina

2016-01-01

Heat treatment is a popular alternative to synthetic pesticides in disinfesting food-processing facilities and empty grain storages. Sitophilus zeamais Mostchulsky is one of the most cosmopolitan and destructive insects found in empty grain storage facilities and processing facilities. The effect of acclimation in S. zeamais adults to sublethal high temperature on their subsequent susceptibility to high temperatures was investigated. S. zeamais adults were acclimated to 36°C for 0 (as a control), 1, 3, and 5 h, and then were exposed at 43, 47, 51, and 55°C for different time intervals respectively. Acclimation to sublethal high temperature significantly reduced subsequent susceptibility of S. zeamais adults to lethal high temperatures of 43, 47, 51, and 55°C, although the mortality of S. zeamais adults significantly increased with increasing exposure time at lethal high temperatures. The mortality of S. zeamais adults with 1, 3, and 5 h of acclimation to 36°C was significantly lower than that of S. zeamais adults without acclimation when exposed to the same lethal high temperatures. The present results suggest that the whole facility should be heated to target lethal high temperature as soon as possible, avoiding decreasing the control effectiveness of heat treatment due to the acclimation in stored product insects to sublethal temperature. PMID:27462906

Repeated exposure to sublethal doses of the organophosphorus compound VX activates BDNF expression in mouse brain.

PubMed

Pizarro, Jose M; Chang, Wenling E; Bah, Mariama J; Wright, Linnzi K M; Saviolakis, George A; Alagappan, Arun; Robison, Christopher L; Shah, Jinesh D; Meyerhoff, James L; Cerasoli, Douglas M; Midboe, Eric G; Lumley, Lucille A

2012-04-01

The highly toxic organophosphorus compound VX [O-ethyl S-[2-(diisopropylamino)ethyl]methylphosphonate] is an irreversible inhibitor of the enzyme acetylcholinesterase (AChE). Prolonged inhibition of AChE increases endogenous levels of acetylcholine and is toxic at nerve synapses and neuromuscular junctions. We hypothesized that repeated exposure to sublethal doses of VX would affect genes associated with cell survival, neuronal plasticity, and neuronal remodeling, including brain-derived neurotrophic factor (BDNF). We examined the time course of BDNF expression in C57BL/6 mouse brain following repeated exposure (1/day × 5 days/week × 2 weeks) to sublethal doses of VX (0.2 LD(50) and 0.4 LD(50)). BDNF messenger RNA expression was significantly (p < 0.05) elevated in multiple brain regions, including the dentate gyrus, CA3, and CA1 regions of the hippocampal formation, as well as the piriform cortex, hypothalamus, amygdala, and thalamus, 72 h after the last 0.4 LD(50) VX exposure. BDNF protein expression, however, was only increased in the CA3 region of the hippocampus. Whether increased BDNF in response to sublethal doses of VX exposure is an adaptive response to prevent cellular damage or a precursor to impending brain damage remains to be determined. If elevated BDNF is an adaptive response, exogenous BDNF may be a potential therapeutic target to reduce the toxic effects of nerve agent exposure.

Sublethal effects of buprofezin on development and reproduction in the white-backed planthopper, Sogatella furcifera (Hemiptera: Delphacidae).

PubMed

Ali, Ehsan; Liao, Xun; Yang, Peng; Mao, Kaikai; Zhang, Xiaolei; Shakeel, Muhammad; Salim, Abdalla M A; Wan, Hu; Li, Jianhong

2017-12-05

In the present study, the effects of sublethal concentrations of buprofezin on life-table traits of S. furcifera were evaluated for two consecutive generations (F0 and F1). Our results exhibited that the fecundity, life span (longevity) and hatchability of the F0 and F1 generations were significantly decreased at LC 30 compared to the control. However, copulation was not significantly affected for the F0 or F1 generations at sublethal concentrations. The female life span was affected negatively at both treatments in F0 and at LC 30 in F1, compared to the control. Furthermore, significant effects of the sublethal concentrations were found on the developmental rate of all instars except the 3 rd instar of F1. However, the pre-adult period, total pre-oviposition period (TPOP) and adult pre-oviposition period (APOP) significantly increased in F1 individuals at LC 30 and LC 10 compared to the control. Our findings revealed that demographic characters (survival rate, intrinsic rate of increase (ri), finite rate of increase (λ), net reproductive rate (R 0 ), and gross reproductive rate (GRR)) of the F1 generation (from F0 parents) significantly decreased compared to the untreated group; however, the generation time (T) increased at LC 10 . Therefore, the results suggested that buprofezin could adversely affect individuals in the successive generation.

Effects of sublethal exposure to zinc chloride on the reproduction of the water flea, Moina irrasa (cladocera)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zou, E.

1997-03-01

As a result of industrial activities, aquatic ecosystems have been contaminated increasingly by metals. Such occurrences pose a threat to aquatic organisms in particular and to the whole ecosystem in general. Because of their importance as part of the food chains in the freshwater ecosystem, as well as their high vulnerability to metal contaminants, the cladoceran crustaceans have attracted attention by toxicologists. The acute toxicity of metals to cladocerans has been well documented by. However, most of the investigations in chronic toxicity deal with metals not essential for life such as mercury and cadmium. It is well known that exposuremore » to mercury and cadmium can generally render inhibitory effects. However, the effects of sublethal exposure of cladocerans to metals such as zinc and selenium, which are essential for life at trace level, are not as well known. As one of the major metal contaminants in freshwater ecosystems, zinc is of ecotoxicological interest. The effects of sublethal zinc exposure, especially at low concentrations, on the reproduction of cladocerans are poorly understood. The objective of this study was to investigate the effects of exposure to a wide range of sublethal concentrations of zinc chloride on the reproduction of Moina irrasa, a cladoceran commonly found in the freshwaters of the Yangtze delta of China. 11 refs., 1 tab.« less

Japanese quail acute exposure to methamidophos: experimental design, lethal, sub-lethal effects and cholinesterase biochemical and histochemical expression.

PubMed

Foudoulakis, Manousos; Balaskas, Christos; Csato, Attila; Szentes, Csaba; Arapis, Gerassimos

2013-04-15

We exposed the Japanese quail (Coturnix coturnix japonica) to the organophosphate methamidophos using acute oral test. Mortality and sub-lethal effects were recorded in accordance to internationally accepted protocols. In addition cholinesterases were biochemically estimated in tissues of the quail: brain, liver and plasma. Furthermore, brain, liver and duodenum cryostat sections were processed for cholinesterase histochemistry using various substrates and inhibitors. Mortalities occurred mainly in the first 1-2h following application. Sub-lethal effects, such as ataxia, ruffled feathers, tremor, salivation and reduced or no reaction to external stimuli were observed. Biochemical analysis in the brain, liver and plasma indicates a strong cholinesterase dependent inhibition with respect to mortality and sub-lethal effects of the quail. The histochemical staining also indicated a strong cholinesterase inhibition in the organs examined and the analysis of the stained sections allowed for an estimation and interpretation of the intoxication effects of methamidophos, in combination with tissue morphology visible by Haematoxylin and Eosin staining. We conclude that the use of biochemistry and histochemistry for the biomarker cholinesterase, may constitute a significantly novel approach for understanding the results obtained by the acute oral test employed in order to assess the effects of methamidophos and other chemicals known to inhibit this very important nervous system enzyme. Copyright © 2012 Elsevier B.V. All rights reserved.

Fumigant Toxicity and Sublethal Effects of Artemisia khorassanica and Artemisia sieberi on Sitotroga cerealella (Lepidoptera: Gelechiidae)

PubMed Central

Abedi, Z; Abdolmaleki, A; Jafary-Jahed, M; Borzoui, E; Mozaffar Mansouri, Seyed

2017-01-01

Abstract Fumigant toxicity and sublethal effects of essential oils from Artemisia khorassanica Podl. and Artemisia sieberi Bess were investigated against adults of Sitotroga cerealella Olivier. To assess the sublethal effects, adult moths were exposed to the LC30 of each essential oil, and life table parameters of the surviving S. cerealella were studied. Higher fumigant toxicity of A. khorassanica (LC50: 7.38 µl/liter air) than A. sieberi (LC50: 9.26 µl/liter air) was observed against S. cerealella. Also, the insecticidal effects of A. khorassanica (LT50: 9.01 h) were faster than A. sieberi (LT50: 14.37 h). A significant extension was observed in the developmental time (egg to adult) of S. cerealella treated with the essential oils. In addition, fecundity of S. cerealella reduced by 25.29 and 35.78% following exposure to sublethal concentrations of A. sieberi and A. khorassanica, respectively. Both tested essential oils caused a significant reduction in the gross and net reproductive rates, intrinsic rate of increase (rm), and finite rate of increase of S. cerealella. The rm values following exposure to A. sieberi, A. khorassanica, and control were 0.098, 0.094, and 0.107 d−1, respectively. The results of this study suggest that tested essential oils have a good potential to apply in integrated pest management of S. cerealella. PMID:29117375

Staphylococcus aureus methicillin resistance detected by HPLC-MS/MS targeted metabolic profiling.

PubMed

Schelli, Katie; Rutowski, Joshua; Roubidoux, Julia; Zhu, Jiangjiang

2017-03-15

Recently, novel bioanalytical methods, such as NMR and mass spectrometry based metabolomics approaches, have started to show promise in providing rapid, sensitive and reproducible detection of Staphylococcus aureus antibiotic resistance. Here we performed a proof-of-concept study focused on the application of HPLC-MS/MS based targeted metabolic profiling for detecting and monitoring the bacterial metabolic profile changes in response to sub-lethal levels of methicillin exposure. One hundred seventy-seven targeted metabolites from over 20 metabolic pathways were specifically screened and one hundred and thirty metabolites from in vitro bacterial tests were confidently detected from both methicillin susceptible and methicillin resistant Staphylococcus aureus (MSSA and MRSA, respectively). The metabolic profiles can be used to distinguish the isogenic pairs of MSSA strains from MRSA strains, without or with sub-lethal levels of methicillin exposure. In addition, better separation between MSSA and MRSA strains can be achieved in the latter case using principal component analysis (PCA). Metabolite data from isogenic pairs of MSSA and MRSA strains were further compared without and with sub-lethal levels of methicillin exposure, with metabolic pathway analyses additionally performed. Both analyses suggested that the metabolic activities of MSSA strains were more susceptible to the perturbation of the sub-lethal levels of methicillin exposure compared to the MRSA strains. Copyright © 2016 Elsevier B.V. All rights reserved.

Selection based on CD133 and high aldehyde dehydrogenase activity isolates long-term reconstituting human hematopoietic stem cells

PubMed Central

Hess, David A.; Wirthlin, Louisa; Craft, Timothy P.; Herrbrich, Phillip E.; Hohm, Sarah A.; Lahey, Ryan; Eades, William C.; Creer, Michael H.; Nolta, Jan A.

2006-01-01

The development of novel cell-based therapies requires understanding of distinct human hematopoietic stem and progenitor cell populations. We recently isolated reconstituting hematopoietic stem cells (HSCs) by lineage depletion and purification based on high aldehyde dehydrogenase activity (ALDHhiLin- cells). Here, we further dissected the ALDHhi-Lin- population by selection for CD133, a surface molecule expressed on progenitors from hematopoietic, endothelial, and neural lineages. ALDHhiCD133+Lin- cells were primarily CD34+, but also included CD34-CD38-CD133+ cells, a phenotype previously associated with repopulating function. Both ALDHhiCD133-Lin- and ALDHhiCD133+Lin- cells demonstrated distinct clonogenic progenitor function in vitro, whereas only the ALDHhiCD133+Lin- population seeded the murine bone marrow 48 hours after transplantation. Significant human cell repopulation was observed only in NOD/SCID and NOD/SCID β2M-null mice that received transplants of ALDHhiCD133+Lin- cells. Limiting dilution analysis demonstrated a 10-fold increase in the frequency of NOD/SCID repopulating cells compared with CD133+Lin- cells, suggesting that high ALDH activity further purified cells with repopulating function. Transplanted ALDHhiCD133+Lin- cells also maintained primitive hematopoietic phenotypes (CD34+CD38-) and demonstrated enhanced repopulating function in recipients of serial, secondary transplants. Cell selection based on ALDH activity and CD133 expression provides a novel purification of HSCs with long-term repopulating function and may be considered an alternative to CD34 cell selection for stem cell therapies. PMID:16269619

RADIATION EFFECTS ON IMMUNE MECHANISMS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stoner, R.D.; Hale, W.M.

1963-03-01

Experiments were performed on pathogen-free Swiss albino mice to determine the repressive effect of ionizing radiation on immune mechanisms. In animals given sublethal doses of Co/sup 60/ gamma radiation by acute short-term exposure or by chronic long-term exposure at a low dose rate, ability to produce antibody was inhibited or abolished, and natural resistance and active and passive immunity to pneumococcal and Trichinella infections were severely depressed. It appears that the repression resulted from damage to the cellular defensive mechanisms of the host. Active immunity and natural resistance to influenza virus infections were not altered significantly by radiation. Exposure tomore » radiation enhanced the severity of anaphylactic shock markedly in mice previously sensitized to tetanus toxoid and challenged with tetanus toxoid after radiation. Chronic exposure to radiation caused immediate increased sensitivity to fatal anaphylaxis. (auth)« less

Genes are differentially expressed at transcriptional level of Neocaridina denticulata following short-term exposure to nonylphenol.

PubMed

Liu, Chang-Lun; Sung, Hung-Hung

2011-09-01

To assess the toxicity of nonylphenol towards aquatic crustaceans, Neocaridina denticulata were exposed short-term to sublethal concentration (0.001-0.5 mg/L). Following treatment, differentially expressed genes were identified using suppression subtractive hybridization on samples prepared from whole specimens. There were 20 differentially expressed sequence tags that corresponded to known genes and could be divided into six functional classes: defence, translation, metabolism, ribosomal gene expression, respiration, and genes involved in the stress response. Using semi-quantitative RT-PCR, we found that 14 of the differentially expressed sequence tags significantly responded to nonylphenol, including six at a nominal concentration of 0.01 mg/L; among them, 12 genes were down-regulated. These results suggest that under non-lethal concentrations of nonylphenol, the polluted aquatic environment may still present a potential risk to N. denticulata.

CD8+ lymphocytes are required to maintain virus suppression in SIV-infected macaques treated with short-term antiretroviral therapy

PubMed Central

Cartwright, Emily K.; Spicer, Lori; Smith, S. Abigail; Lee, David; Fast, Randy; Paganini, Sara; Lawson, Benton O.; Nega, Melon; Easley, Kirk; Schmitz, Joern E.; Bosinger, Steven E.; Paiardini, Mirko; Chahroudi, Ann; Vanderford, Thomas H.; Estes, Jacob D.; Lifson, Jeffrey D.; Derdeyn, Cynthia A.; Silvestri, Guido

2016-01-01

Infection with HIV persists despite suppressive antiretroviral therapy (ART) and treatment interruption results in rapid viral rebound. Antibody-mediated CD8+ lymphocyte depletion in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) shows these cells contribute to virus control in untreated animals. However, the contribution of CD8+ lymphocytes to maintaining virus suppression under ART remains unknown. We showed that in SIV-infected RMs treated with short-term ART (i.e., 8-32 weeks), depletion of CD8+ lymphocytes resulted in increased plasma viremia in all animals, and that repopulation of CD8+ T cells was associated with prompt reestablishment of virus control. Although the number of SIV-DNA-positive cells remained unchanged after CD8 depletion and reconstitution, the frequency of SIV-infected CD4+ T cells pre-depletion positively correlated with both peak and area-under-the-curve of viremia post-depletion. These results suggest a role for CD8+ T cells in controlling virus production during ART, thus providing rationale to explore immunotherapeutic approaches in ART-treated HIV-infected individuals. PMID:27653601

Thermal inactivation and sublethal injury kinetics of Salmonella enterica and Listeria monocytogenes in broth versus agar surface.

PubMed

Wang, Xiang; Devlieghere, Frank; Geeraerd, Annemie; Uyttendaele, Mieke

2017-02-21

The objective of the present study was to compare the thermal inactivation and sublethal injury kinetics of Salmonella enterica and Listeria monocytogenes in broth (suspended cells) and on solid surface (agar-seeded cells). A 3-strain cocktail of S. enterica or L. monocytogenes inoculated in broth or on agar was subjected to heating in a water bath at various set temperatures (55.0, 57.5 and 60.0°C for S. enterica and 60.0, 62.5 and 65°C for L. monocytogenes). The occurrence of sublethally injured cells was determined by comparing enumerations on nonselective (TSAYE) and selective (XLD or ALOA) media. Results showed that the inactivation curves obtained from selective media were log-linear, and significant shoulders (p<0.05) were observed on some of the inactivation curves from TSAYE media. The D-values derived from the total population were higher than those from the uninjured cells. Generally, cells on agar surface exhibited higher heat resistance than those in broth. For S. enterica, cell injury increased with the exposure time, no difference was observed when treated at temperatures from 55.0 to 60.0°C, while for L. monocytogenes, cell injury increased significantly with heating time and treatment temperature (from 60.0 to 65°C). Moreover, the degree of sublethal injury affected by thermal treatment in broth or on agar surface depended upon the target microorganism. Higher proportions of injured S. enterica cells were observed for treatment in broth than on agar surface, while the opposite was found for L. monocytogenes. The provided information may be used to assess the efficacy of thermal treatment processes on surfaces for inactivation of S. enterica and L. monocytogenes, and it provides insight into the sublethally injured survival state of S. enterica and L. monocytogenes treated in liquid or on solid food. Copyright © 2016 Elsevier B.V. All rights reserved.

Pregnancy persistently affects memory T cell populations.

PubMed

Kieffer, Tom E C; Faas, Marijke M; Scherjon, Sicco A; Prins, Jelmer R

2017-02-01

Pregnancy is an immune challenge to the maternal immune system. The effects of pregnancy on maternal immunity and particularly on memory T cells during and after pregnancy are not fully known. This observational study aims to show the short term and the long term effects of pregnancy on the constitution, size and activation status of peripheral human memory T-lymphocyte populations. Effector memory (EM) and central memory (CM) T-lymphocytes were analyzed using flow cytometry of peripheral blood from 14 nulligravid, 12 primigravid and 15 parous women that were on average 18 months postpartum. The short term effects were shown by the significantly higher CD4+ EM cell and activated CD4+ memory cell proportions in primigravid women compared to nulligravid women. The persistent effects found in this study were the significantly higher proportions of CD4+ EM, CD4+ CM and activated memory T cells in parous women compared to nulligravid women. In contrast to CD4+ cells, activation status of CD8+ memory cells did not differ between the groups. This study shows that pregnancy persistently affects the pre-pregnancy CD4+ memory cell pool in human peripheral blood. During pregnancy, CD4+ T-lymphocytes might differentiate into EM cells followed by persistent higher proportions of CD4+ CM and EM cells postpartum. The persistent effects of pregnancy on memory T cells found in this study support the hypothesis that memory T cells are generated during pregnancy and that these cells could be involved in the lower complication risks in multiparous pregnancies in humans. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

IL-7 promotes long-term in vitro survival of unique long-lived memory subset generated from mucosal effector memory CD4+ T cells in chronic colitis mice.

PubMed

Takahara, Masahiro; Nemoto, Yasuhiro; Oshima, Shigeru; Matsuzawa, Yu; Kanai, Takanori; Okamoto, Ryuichi; Tsuchiya, Kiichiro; Nakamura, Tetsuya; Yamamoto, Kazuhide; Watanabe, Mamoru

2013-01-01

Colitogenic memory CD4(+) T cells are important in the pathogenesis of inflammatory bowel disease (IBD). Although memory stem cells with high survival and self-renewal capacity were recently identified in both mice and humans, it is unclear whether a similar subset is present in chronic colitis mice. We sought to identify and purify a long-lived subset of colitogenic memory CD4(+) T cells, which may be targets for treatment of IBD. A long-lived subset of colitogenic memory CD4(+) T cells was purified using a long-term culture system. The characteristics of these cells were assessed. Interleukin (IL)-7 promoted the in vitro survival for >8 weeks of lamina propria (LP) CD4(+) T cells from colitic SCID mice previously injected with CD4(+)CD45RB(high) T cells. These cells were in a quiescent state and divided a maximum of 5 times in 4 weeks. LP CD4(+) T cells expressed higher levels of Bcl-2, integrin-α4β7, CXCR3 and CD25 after than before culture, as well as secreting high concentrations of IL-2 and low concentrations of IFN-γ and IL-17 in response to intestinal bacterial antigens. LP CD4(+) T cells from colitic mice cultured with IL-7 for 8 weeks induced more severe colitis than LP CD4(+) T cells cultured for 4 weeks. We developed a novel culture system to purify a long-lived, highly pathogenic memory subset from activated LP CD4(+) T cells. IL-7 promoted long-term in vitro survival of this subset in a quiescent state. This subset will be a novel, effective target for the treatment of IBD. Copyright © 2013 Elsevier B.V. All rights reserved.

[Sublethal microcephalic chondrodysplasia. Taybi-Linder syndrome, primordial microcephalic nanism types I and III].

PubMed

Maroteaux, P; Badoual, J

1990-02-01

The authors describe a case of microcephalic dwarfism observed in a newborn until 10 months of age and discuss the diagnostic challenge. They show that the Taybi-Linder syndrome and the primordial dwarfism type I and type III of Majewski are an identical recessive autosomal entity. The radiological evolution explains the initial separation of type I and type III. Because of the skeletal lesions, lacking in the Seckel syndrome, the name of sublethal microcephalic chondrodysplasia is proposed for this disease.

Some physiological aspects of sublethal heat stress in the juvenile steelhead trout (Salmo gairdneri) and coho salmon (Oncorhynchus kisutch)

USGS Publications Warehouse

Wedemeyer, Gary

1973-01-01

A rapid (3 min) but sublethal temperature increase from 10 to 20 imposed a greater stress on juvenile coho salmon (Oncorhynchus kisutch) than on juvenile steelhead trout (Salmo gairdneri). Both species suffered hyperglycemia, hypocholesterolemia, increased blood hemoglobin, and decreased blood sugar regulatory precision, but the steelhead recovered more quickly. Acid–base equilibrium was essentially unaffected, and only the coho suffered any significant interrenal vitamin C depletion. Vitamin C normalization required about 24 hr.

Effects of long-term fertilization practices on heavy metal cadmium accumulation in the surface soil and rice plants of double-cropping rice system in Southern China.

PubMed

Xu, Yilan; Tang, Haiming; Liu, Tangxing; Li, Yifeng; Huang, Xinjie; Pi, Jun

2018-05-08

Fertilizer regime is playing an important role in heavy metal cadmium (Cd) accumulation in paddy soils and crop plant. It is necessary to assess the Cd accumulation in soils and rice (Oryza sativa L.) plants under long-term fertilization managements, and the results which help to assess the environmental and food risk in Southern China. However, the effects of different organic manure and chemical fertilizers on Cd accumulation in soils and rice plant remain unclear under intensively cultivated rice conditions. Therefore, the objective was to explore Cd accumulation in paddy soils and rice plant at mature stage under different long-term fertilization managements in the double-cropping rice system. Cd accumulation in the surface soils (0-20 cm) and rice plant with chemical fertilizer alone (MF), rice straw residue and chemical fertilizer (RF), 30% organic matter and 70% chemical fertilizer (LOM), 60% organic matter and 40% chemical fertilizer (HOM), and without fertilizer input (CK) basis on 32 years long-term fertilization experiment were analyzed. The results showed that the soil total Cd content was increased by 0.296 and 0.351 mg kg -1 and 0.261 and 0.340 mg kg -1 under LOM and HOM treatments at early and late rice mature stages, respectively, compared with the CK treatment. And the soil available Cd content was increased by 0.073 and 0.137 mg kg -1 and 0.102 and 0.160 mg kg -1 under LOM and HOM treatments at early and late rice mature stages, respectively, compared with the CK treatment. The bioconcentration factor of Cd across different parts of rice plant was the highest in root, followed by stem and grain, and the lowest in leaves. At early and late rice mature stages, the root Cd concentration of rice plant was increased by 0.689 and 0.608 mg kg -1 with HOM treatment, the stem Cd concentration of rice plant was increased by 0.666 and 0.758 mg kg -1 with RF treatment, and the leaf and grain Cd concentration of rice plant was increased 0.094 and 0.082 mg kg -1 and 0.086 and 0.083 mg kg -1 with LOM treatment, respectively, compared with the CK treatment. The soil Cd single-factor contaminant index (P Cd ) under different fertilization treatments was as the following HOM > LOM > RF > MF > CK. Meanwhile, the P Cd with LOM and HOM treatments was higher than that of the MF, RF, and CK treatments, but there is no significant difference between that of MF and RF treatments. Therefore, long-term application of rice straw residue and chemical fertilizer had no obvious effect on the accumulation of Cd in paddy soils and grain, and soil Cd accumulation was increased as application of organic fertilizer.

SLAM family markers are conserved among hematopoietic stem cells from old and reconstituted mice and markedly increase their purity

PubMed Central

Yilmaz, Ömer H.; Kiel, Mark J.; Morrison, Sean J.

2006-01-01

Recent advances have increased the purity of hematopoietic stem cells (HSCs) isolated from young mouse bone marrow. However, little attention has been paid to the purity of HSCs from other contexts. Although Thy-1lowSca-1+Lineage-c-kit+ cells from young bone marrow are highly enriched for HSCs (1 in 5 cells gives long-term multilineage reconstitution after transplantation into irradiated mice), the same population from old, reconstituted, or cytokine-mobilized mice engrafts much less efficiently (1 in 78 to 1 in 185 cells gives long-term multilineage reconstitution). To test whether we could increase the purity of HSCs isolated from these contexts, we examined the SLAM family markers CD150 and CD48. All detectable HSCs from old, reconstituted, and cyclophosphamide/G-CSF-mobilized mice were CD150+CD48-, just as in normal young bone marrow. Thy-1lowSca-1+Lineage-c-kit+ cells from old, reconstituted, or mobilized mice included mainly CD48+ and/or CD150- cells that lacked reconstituting ability. CD150+CD48-Sca-1+Lineage-c-kit+ cells from old, reconstituted, or mobilized mice were much more highly enriched for HSCs, with 1 in 3 to 1 in 7 cells giving long-term multilineage reconstitution. SLAM family receptor expression is conserved among HSCs from diverse contexts, and HSCs from old, reconstituted, and mobilized mice engraft relatively efficiently after transplantation when contaminating cells are eliminated. PMID:16219798

SLAM family markers are conserved among hematopoietic stem cells from old and reconstituted mice and markedly increase their purity.

PubMed

Yilmaz, Omer H; Kiel, Mark J; Morrison, Sean J

2006-02-01

Recent advances have increased the purity of hematopoietic stem cells (HSCs) isolated from young mouse bone marrow. However, little attention has been paid to the purity of HSCs from other contexts. Although Thy-1 low Sca-1+ Lineage- c-kit+ cells from young bone marrow are highly enriched for HSCs (1 in 5 cells gives long-term multilineage reconstitution after transplantation into irradiated mice), the same population from old, reconstituted, or cytokine-mobilized mice engrafts much less efficiently (1 in 78 to 1 in 185 cells gives long-term multilineage reconstitution). To test whether we could increase the purity of HSCs isolated from these contexts, we examined the SLAM family markers CD150 and CD48. All detectable HSCs from old, reconstituted, and cyclophosphamide/G-CSF-mobilized mice were CD150+ CD48-, just as in normal young bone marrow. Thy-1 low Sca-1+ Lineage- c-kit+ cells from old, reconstituted, or mobilized mice included mainly CD48+ and/or CD150- cells that lacked reconstituting ability. CD150+ CD48- Sca-1+ Lineage- c-kit+ cells from old, reconstituted, or mobilized mice were much more highly enriched for HSCs, with 1 in 3 to 1 in 7 cells giving long-term multilineage reconstitution. SLAM family receptor expression is conserved among HSCs from diverse contexts, and HSCs from old, reconstituted, and mobilized mice engraft relatively efficiently after transplantation when contaminating cells are eliminated.

Systemic Delivery of Microencapsulated 3-Bromopyruvate for the Therapy of Pancreatic Cancer

PubMed Central

Chapiro, Julius; Sur, Surojit; Savic, Lynn Jeanette; Ganapathy-Kanniappan, Shanmugasundaram; Reyes, Juvenal; Duran, Rafael; Thiruganasambandam, Sivarajan Chettiar; Moats, Cassandra Rae; Lin, MingDe; Luo, Weibo; Tran, Phuoc T.; Herman, Joseph M.; Semenza, Gregg L.; Ewald, Andrew J.; Vogelstein, Bert; Geschwind, Jean-François

2015-01-01

Purpose This study characterized the therapeutic efficacy of a systemically administered formulation of 3-bromopyruvate (3-BrPA), microencapsulated in a complex with β-cyclodextrin (β-CD), using an orthotopic xenograft mouse model of pancreatic ductal adenocarcinoma (PDAC). Experimental Design The presence of the β-CD–3-BrPA complex was confirmed using nuclear magnetic resonance spectroscopy. Monolayer as well as three-dimensional organotypic cell culture was used to determine the half-maximal inhibitory concentrations (IC50) of β-CD–3-BrPA, free 3-BrPA, β-CD (control), and gemcitabine in MiaPaCa-2 and Suit-2 cell lines, both in normoxia and hypoxia. Phase-contrast microscopy, bioluminescence imaging (BLI), as well as zymography and Matrigel assays were used to characterize the effects of the drug in vitro. An orthotopic lucMiaPaCa-2 xenograft tumor model was used to investigate the in vivo efficacy. Results β-CD–3-BrPA and free 3-BrPA demonstrated an almost identical IC50 profile in both PDAC cell lines with higher sensitivity in hypoxia. Using the Matrigel invasion assay as well as zymography, 3-BrPA showed anti-invasive effects in sublethal drug concentrations. In vivo, animals treated with β-CD–3-BrPA demonstrated minimal or no tumor progression as evident by the BLI signal as opposed to animals treated with gemcitabine or the β-CD (60-fold and 140-fold signal increase, respectively). In contrast to animals treated with free 3-BrPA, no lethal toxicity was observed for β-CD–3-BrPA. Conclusion The microencapsulation of 3-BrPA represents a promising step towards achieving the goal of systemically deliverable antiglycolytic tumor therapy. The strong anticancer effects of β-CD–3-BrPA combined with its favorable toxicity profile suggest that clinical trials, particularly in patients with PDAC, should be considered. PMID:25326230

Dysregulated miR34a/diacylglycerol kinase ζ interaction enhances T-cell activation in acquired aplastic anemia.

PubMed

Sun, Yuan-Xin; Li, Hui; Feng, Qi; Li, Xin; Yu, Ying-Yi; Zhou, Li-Wei; Gao, Yan; Li, Guo-Sheng; Ren, Juan; Ma, Chun-Hong; Gao, Cheng-Jiang; Peng, Jun

2017-01-24

Acquired aplastic anemia is an idiopathic paradigm of human bone marrow failure syndrome, which involves active destruction of hematopoietic stem cells and progenitors by cytotoxic T cells in the bone marrow. Aberrant expression of microRNAs in T cells has been shown to lead to development of certain autoimmune diseases. In the present study, we performed a microarray analysis of miRNA expression in bone marrow CD3+ T cells from patients with aplastic anemia and healthy controls. Overexpression of miR34a and underexpression of its target gene diacylglycerol kinase (DGK) ζ in bone marrow mononuclear cells were validated in 41 patients and associated with the severity of aplastic anemia. Further, the level of miR34a was higher in naïve T cells from patients than from controls. The role of miR34a and DGKζ in aplastic anemia was investigated in a murine model of immune-mediated bone marrow failure using miR34a-/- mice. After T-cell receptor stimulation in vitro, lymph node T cells from miR34a-/- mice demonstrated reduced activation and proliferation accompanied with a less profound down-regulation of DGKζ expression and decreased ERK phosphorylation compared to those from wild-type C57BL6 control mice. Infusion of 5 × 106 miR34a-/- lymph node T cells into sublethally irradiated CB6F1 recipients led to increased Lin-Sca1+CD117+ cells and less vigorous expansion of CD8+ T cells than injection of same number of wild-type lymph node cells. Our study demonstrates that the miR34a/DGKζ dysregulation enhances T-cell activation in aplastic anemia and targeting miR34a may represent a novel molecular therapeutic approach for patients with aplastic anemia.

Predicting plant uptake of cadmium: validated with long-term contaminated soils.

PubMed

Lamb, Dane T; Kader, Mohammed; Ming, Hui; Wang, Liang; Abbasi, Sedigheh; Megharaj, Mallavarapu; Naidu, Ravi

2016-10-01

Cadmium accumulates in plant tissues at low soil loadings and is a concern for human health. Yet at higher levels it is also of concern for ecological receptors. We determined Cd partitioning constants for 41 soils to examine the role of soil properties controlling Cd partitioning and plant uptake. From a series of sorption and dose response studies, transfer functions were developed for predicting Cd uptake in Cucumis sativa L. (cucumber). The parameter log K f was predicted with soil pH ca , logCEC and log OC. Transfer of soil pore-water Cd 2+ to shoots was described with a power function (R 2  = 0.73). The dataset was validated with 13 long-term contaminated soils (plus 2 control soils) ranging in Cd concentration from 0.2 to 300 mg kg -1 . The series of equations predicting Cd shoot from pore-water Cd 2+ were able to predict the measured data in the independent dataset (root mean square error = 2.2). The good relationship indicated that Cd uptake to cucumber shoots could be predicted with Cd pore and Cd 2+ without other pore-water parameters such as pH or Ca 2+ . The approach may be adapted to a range of plant species.

Isotope Tracing of Long-Term Cadmium Fluxes in an Agricultural Soil.

PubMed

Salmanzadeh, Mahdiyeh; Hartland, Adam; Stirling, Claudine H; Balks, Megan R; Schipper, Louis A; Joshi, Chaitanya; George, Ejin

2017-07-05

Globally widespread phosphate fertilizer applications have resulted in long-term increases in the concentration of cadmium (Cd) in soils. The accumulation of this biotoxic, and bioaccumulative metal presents problems for the management of soil-plant-animal systems, because the magnitude and direction of removal fluxes (e.g., crop uptake, leaching) have been difficult to estimate. Here, Cd isotopic compositions (δ 114/110 Cd) of archived fertilizer and soil samples from a 66 year-long agricultural field trial in Winchmore, New Zealand, were used to constrain the Cd soil mass balance between 1959 and 2015 AD, informing future soil Cd accumulation trajectories. The isotopic partitioning of soil Cd sources in this system was aided by a change in phosphate source rocks in 1998 AD, and a corresponding shift in fertilizer isotope composition. The dominant influence of mixing between isotopically distinct Cd end-members was confirmed by a Bayesian modeling approach. Furthermore, isotope mass balance modeling revealed that Cd removal processes most likely increased in magnitude substantially between 2000 and 2015 AD, implying an increase in Cd bioaccumulation and/or leaching over that interval. Natural-abundance stable isotopes are introduced here as a powerful tool for tracing the fate of Cd in agricultural soils, and potentially the wider environment.

A Novel Double Subculture Method and Its Theory for the Enumeration of Injured Cells in Stressed Microbial Population.

PubMed

Tsuchido, Tetsuaki

2017-01-01

　A novel double subculture method, termed DiVSaL (Differential Viabilities between Solid and Liquid media) method, for the enumeration of injured cell population of a microorganism, which occurs after some sublethal to lethal treatment, was proposed. In this method injured cells were enumerated as the differential value between viabilities determined with two different techniques, the conventional plate counting using a solid agar medium and the growth delay analysis using a liquid medium. In the former technique, the viable cell number is obtained as colony forming unit (CFU) formed on an agar medium where sublethally injured cells are as much rescued as possible. In the latter technique, on the other hand," the integrated viability" defined by Takano and Tsuchido (1982) is introduced and is calculated from the growth delay of a stressed population, referred to unstressed one. For the growth delay analysis, in this paper, not only the original theoretical model, where the specific growth rate (and therefore the defined G 10 value) does not change after the exposure to a stress treatment, but also a novel modified theory, where the parameter changes, is proposed. On the theoretical background, this DiVSaL method as a double subculture method can be used to enumerate the injured cells without selection by addition of some inhibitor or by nutritional shortage.

Effects of sublethal fenitrothion ingestion on cholinesterase inhibition, standard metabolism, thermal preference, and prey-capture ability in the Australian central bearded dragon (Pogona vitticeps, Agamidae).

PubMed

Bain, David; Buttemer, William A; Astheimer, Lee; Fildes, Karen; Hooper, Michael J

2004-01-01

The central bearded dragon (Pogona vitticeps) is a medium-sized lizard that is common in semiarid habitats in Australia and that potentially is at risk of fenitrothion exposure from use of the chemical in plague locust control. We examined the effects of single sublethal doses of this organophosphate (OP; low dose = 2.0 mg/kg; high dose = 20 mg/kg; control = vehicle alone) on lizard thermal preference, standard metabolic rate, and prey-capture ability. We also measured activities of plasma total cholinesterase (ChE) and acetylcholinesterase before and at 0, 2, 8, 24, 120, and 504 h after OP dosing. Predose plasma total ChE activity differed significantly between sexes and averaged 0.66 +/- 0.06 and 0.45 +/- 0.06 micromol/min/ml for males and females, respectively. Approximately 75% of total ChE activity was attributable to butyrylcholinesterase. Peak ChE inhibition reached 19% 2 h after OP ingestion in the low-dose group, and 68% 8 h after ingestion in high-dose animals. Neither OP doses significantly affected diurnal body temperature, standard metabolic rate, or feeding rate. Plasma total ChE levels remained substantially depressed up to 21 d after dosing in the high-dose group, making this species a useful long-term biomonitor of OP exposure in its habitat.

Alterations in carbohydrates and the protein metabolism of the harmful freshwater vector snail Lymnaea acuminata induced by the Euphorbia tirucalli latex extract.

PubMed

Tiwari, Sudhanshu; Singh, A

2005-11-01

To know the short- as well as long-term effect of aqueous latex extracts of Euphorbia tirucalli on carbohydrate and protein metabolism, the snail Lymnaea acuminata was exposed to sublethal doses of 0.37 and 0.55 mg/L for a 24-h and 0.20 and 0.31 mg/L for a 96-h exposure period. Significant (P<0.05) alterations in the glycogen, pyruvate, lactate, total protein, and free amino acid level, as well as in the activity of enzyme lactic dehydrogenase, succinic dehydrogenase, cytochrome oxidase, protease, aspartate aminotransaminase, and alanine aminotransaminase were observed in the nervous, hepatopancreatic, and ovotestis tissues of the freshwater vector snail L. acuminata exposed to sublethal doses of E. tirucalli latex extract. The alterations in all biochemical parameters were significantly (P<0.05) time and dose dependent. After the 7th day of the withdrawal of treatment, there was significant (P<0.05) recovery in glycogen, pyruvate, lactate, total protein, and the free amino acid level and in the activity of the lactic dehydrogenase, succinic dehydrogenase, cytochrome oxidase, protease, aspartate aminotransaminase and alanine aminotransaminase enzymes in all three of the studied tissues of the snail, which supports the view that the plant product is safe for use as a molluscicide for the control of harmful freshwater vector snails in the aquatic environment.

Bacterial bioluminescence response to long-term exposure to reverse osmosis treated effluents from dye industries.

PubMed

Ravindran, J; Manikandan, B; Shirodkar, P V; Francis, K X; Mani Murali, R; Vethamony, P

2014-10-01

The bacterial bioluminescence assay is one of the novel means for toxicity detection. The bioluminescence response of 2 marine bioluminescent bacteria was tested upon their long-term exposure to 9 different reverse osmosis (RO) rejects with varying chemical composition sampled from various dye industries. Bioluminescent bacteria were cultured in the RO reject samples, at different concentrations, and their growth rate and luminescence was measured for 24 h. The RO reject samples caused sublethal effects upon exposure and retarded the growth of bacteria, confirming their toxic nature. Further, continuation of the exposure showed that the initial luminescence, though reduced, recovered and increased beyond the control cultures irrespective of cell density, and finally decreased once again. The present study emphasizes the need of evolving a long-term exposure assay and shows that the method followed in this study is suitable to evaluate the toxicants that exert delayed toxicity, using lower concentrations of toxicants as well as coloured samples.

Sublethal doses of imidacloprid disrupt sexual communication and host finding in a parasitoid wasp

NASA Astrophysics Data System (ADS)

Tappert, Lars; Pokorny, Tamara; Hofferberth, John; Ruther, Joachim

2017-02-01

Neonicotinoids are widely used insecticides, but their use is subject of debate because of their detrimental effects on pollinators. Little is known about the effect of neonicotinoids on other beneficial insects such as parasitoid wasps, which serve as natural enemies and are crucial for ecosystem functioning. Here we show that sublethal doses of the neonicotinoid imidacloprid impair sexual communication and host finding in the parasitoid wasp Nasonia vitripennis. Depending on the dose, treated females were less responsive to the male sex pheromone or unable to use it as a cue at all. Courtship behaviour of treated couples was also impeded resulting in a reduction of mating rates by up to 80%. Moreover, treated females were no longer able to locate hosts by using olfactory cues. Olfaction is crucial for the reproductive success of parasitoid wasps. Hence, sublethal doses of neonicotinoids might compromise the function of parasitoid wasps as natural enemies with potentially dire consequences for ecosystem services.

Histopathology of the fish Corydoras paleatus contaminated with sublethal levels of organophosphorus in water and food.

PubMed

Fanta, Edith; Rios, Flávia Sant'Anna; Romão, Silvia; Vianna, Ana Cristina Casagrande; Freiberger, Sandra

2003-02-01

The effects of contamination, through water or food, of a sublethal dose of the organophosphate methyl parathion were analyzed in tissues that are responsible for absorption (gills, intestine) and metabolism (liver), in the freshwater fish Corydoras paleatus. In gill respiratory lamellae, epithelial hyperplasia, edema, and detachment occurred, diminishing sooner after contamination by food than after contamination through water. In the intestine, lipoid vacuolization of enterocytes, apical cytoplasm, and an increase in goblet cell activity occurred mainly after ingestion of contaminated food. The liver exhibited cloudy swelling, bile stagnation, focal necrosis, atrophy, and vacuolization after contamination through both absorption routes, the highest degeneration being between T(8) and T(24). Metabolic processes that depend on liver function were equally impaired by the two routes of contamination, but secondary effects vary with gill and intestine pathologies as a consequence of water and food contamination, respectively. Therefore, a "safe" sublethal dose of methyl parathion causes serious health problems in C. paleatus.

Potential hepatic toxicity of buprofezin at sublethal concentrations: ROS-mediated conversion of energy metabolism.

PubMed

Ji, Xiaotong; Ku, Tingting; Zhu, Na; Ning, Xia; Wei, Wei; Li, Guangke; Sang, Nan

2016-12-15

Buprofezin is known for its broad-spectrum action and environmental safety. The popularity of buprofezin has raised concerns about its potentially adverse effects on human health and risk to the environment. In this study, we first identified the liver as one of the major organs in which buprofezin accumulated, and we detected a severe oxidative stress response. Next, we demonstrated that sublethal concentrations of buprofezin promoted the conversion of energy metabolism from the aerobic tricarboxylic acid (TCA) cycle and oxidative phosphorylation to anaerobic glycolysis. Importantly, reactive oxygen species (ROS) generation partially accounted for the shunting of the energy metabolism through the buprofezin-mediated inhibition of cytochrome c oxidase activity. ROS directly perturbed the activities of several key TCA cycle enzymes, stimulated glycolysis, and indirectly disturbed the activity of the respiratory chain complex by altering mitochondrial DNA (mtDNA). These findings clarify the potential mechanisms of buprofezin toxicity and provide biomarkers for buprofezin-mediated hepatotoxicity at sublethal concentrations. Copyright © 2016 Elsevier B.V. All rights reserved.

Gene expression changes in honey bees induced by sublethal imidacloprid exposure during the larval stage.

PubMed

Wu, Ming-Cheng; Chang, Yu-Wen; Lu, Kuang-Hui; Yang, En-Cheng

2017-09-01

Honey bee larvae exposed to sublethal doses of imidacloprid show behavioural abnormalities as adult insects. Previous studies have demonstrated that this phenomenon originates from abnormal neural development in response to imidacloprid exposure. Here, we further investigated the global gene expression changes in the heads of newly emerged adults and observed that 578 genes showed more than 2-fold changes in gene expression after imidacloprid exposure. This information might aid in understanding the effects of pesticides on the health of pollinators. For example, the genes encoding major royal jelly proteins (MRJPs), a group of multifunctional proteins with significant roles in the sustainable development of bee colonies, were strongly downregulated. These downregulation patterns were further confirmed through analyses using quantitative reverse transcription-polymerase chain reaction on the heads of 6-day-old nurse bees. To our knowledge, this study is the first to demonstrate that sublethal doses of imidacloprid affect mrjp expression and likely weaken bee colonies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Both genome and cytosol dynamics change in E. coli challenged with sublethal rifampicin

NASA Astrophysics Data System (ADS)

Wlodarski, Michal; Raciti, Bianca; Kotar, Jurij; Cosentino Lagomarsino, Marco; Fraser, Gillian M.; Cicuta, Pietro

2017-02-01

While the action of many antimicrobial drugs is well understood at the molecular level, a systems-level physiological response to antibiotics remains largely unexplored. This work considers fluctuation dynamics of both the chromosome and cytosol in Escherichia coli, and their response to sublethal treatments of a clinically important antibiotic, rifampicin. We precisely quantify the changes in dynamics of chromosomal loci and cytosolic aggregates (a rheovirus nonstructural protein known as μNS-GFP), measuring short time-scale displacements across several hours of drug exposure. To achieve this we develop an empirical method correcting for photo-bleaching and loci size effects. This procedure allows us to characterize the dynamic response to rifampicin in different growth conditions, including a customised microfluidic device. We find that sub-lethal doses of rifampicin cause a small but consistent increase in motility of both the chromosomal loci and cytosolic aggregates. Chromosomal and cytosolic responses are consistent with each other and between different growth conditions.

Combination of counterpropagation artificial neural networks and antioxidant activities for comprehensive evaluation of associated-extraction efficiency of various cyclodextrins in the traditional Chinese formula Xue-Zhi-Ning.

PubMed

Sun, Lili; Yang, Jianwen; Wang, Meng; Zhang, Huijie; Liu, Yanan; Ren, Xiaoliang; Qi, Aidi

2015-11-10

Xue-Zhi-Ning (XZN) is a widely used traditional Chinese medicine formula to treat hyperlipidemia. Recently, cyclodextrins (CDs) have been extensively used to minimize problems relative to medicine bioavailability, such as low solubility and poor stability. The objective of this study was to determine the associated-extraction efficiency of various CDs in XZN. Three various type CDs were evaluated, including native CDs (α-CD, β-CD), hydrophilic CD derivatives (HP-β-CD and Me-β-CD), and ionic CD derivatives (SBE-β-CD and CM-β-CD). An ultra high-performance liquid chromatography (UHPLC) fingerprint was applied to determine the components in CD extracts and original aqueous extract (OAE). A counterpropagation artificial neural network (CP-ANN) was used to analyze the components in different extracts and compare the selective extraction of various CDs. Extraction efficiencies of the various CDs in terms of extracted components follow the ranking, ionic CD derivatives>hydrophilic CD derivatives>native CDs>OAE. Besides, different types of CDs have their own selective extraction and ionic CD derivatives present the strongest associated-extraction efficiency. Antioxidant potentials of various extracts were evaluated by determining the inhibition of spontaneous, H2O2-induced, CCl4-induced and Fe(2+)/ascorbic acid-induced lipid peroxidation (LPO) and analyzing the scavenging capacity for DPPH and hydroxyl radicals. The order of extraction efficiencies of the various CDs relative to antioxidant activities is as follows: SBE-β-CD>CM-β-CD>HP-β-CD>Me-β-CD>β-CD>α-CD. It can be demonstrated that all of the CDs studied increase the extraction efficiency and that ionic CD derivatives (SBE-β-CD and CM-β-CD) present the highest extraction capability in terms of amount extracted and antioxidant activities of extracts. Copyright © 2015 Elsevier B.V. All rights reserved.

Distinctions Among Circulating Antibody Secreting Cell Populations, Including B-1 Cells, in Human Adult Peripheral Blood1

PubMed Central

Quách, Tâm D.; Rodríguez-Zhurbenko, Nely; Hopkins, Thomas J.; Guo, Xiaoti; Vázquez, Ana María Hernández; Li, Wentian; Rothstein, Thomas L.

2015-01-01

Human antibody secreting cell (ASC) populations in circulation are not well studied. In addition to B-1 (CD20+CD27+CD38lo/intCD43+) cell and the conventional plasmablast (CD20-CD27hiCD38hi) cell populations, here we identified a novel B cell population termed 20+38hi B cells (CD20+CD27hiCD38hi) that spontaneously secretes antibody. At steady state, 20+38hi B cells are distinct from plasmablasts on the basis of CD20 expression, amount of antibody production, frequency of mutation, and diversity of B cell receptor repertoire. However, cytokine treatment of 20+38hi B cells induces loss of CD20 and acquisition of CD138, suggesting that 20+38hi B cells are precursors to plasmablasts, or pre-plasmablasts. We then evaluated similarities and differences between CD20+CD27+CD38lo/intCD43+ B-1 cells, CD20+CD27hiCD38hi 20+38hi B cells, CD20-CD27hiCD38hi plasmablasts, and CD20+CD27+CD38lo/intCD43- memory B cells. We found that B-1 cells differ from 20+38hi B cells and plasmablasts in numbers of ways, including antigen expression, morphological appearance, transcriptional profiling, antibody skewing, antibody repertoire, and secretory response to stimulation. In terms of gene expression, B-1 cells align more closely with memory B cells than with 20+38hi B cells or plasmablasts, but differ in that memory B cells do not express antibody secretion related genes. We found that, B-1 cell antibodies utilize Vh4-34, which is often associated with autoreactivity, 3 to 6-fold more often than other B cell populations. Along with selective production of IgM anti-PC, this data suggests that human B-1 cells might be preferentially selected for autoreactivity/natural-specificity. In sum, our results indicate that human healthy adult peripheral blood at steady state consists of 3 distinct ASC populations. PMID:26740107

Optimization of myocardial deformation imaging in term and preterm infants.

PubMed

Poon, Chuen Y; Edwards, Julie M; Joshi, Suchita; Kotecha, Sailesh; Fraser, Alan G

2011-03-01

Myocardial deformation imaging is now used to assess regional ventricular function in infants but their small size presents particular technical challenges. We therefore investigated the determinants of reproducibility of myocardial longitudinal strain (ε) in term and preterm infants, in order to determine optimal technical settings. Repeated longitudinal ε measurements of the mid-segments of the septum, and the left and right ventricular free walls, were performed using five different computation distances (CDs; also called strain length) in 20 infants. The coefficients of variation (CV) were calculated for each CD. Overall, ε measurements were most reproducible with a CD of 6 mm (CV 11.7%). In preterm infants (<34 weeks gestation; mean ± SD diastolic LV length, 20.3 ± 3.5 mm), ε measurements were most reproducible with CD of 6 mm (CV 7.2%); in term infants (>37 weeks gestation; mean ± SD diastolic LV length, 29.6 ± 3.0 mm), ε measurements were most reproducible with CD of 10 mm (CV 13.2%). The reproducibility of measuring ε increased with higher frame rates, from CV of 17.3% at frame rates <180 per s to 11.7% for frame rates >180 per s and 9.6% for rates >248 per s. In newborn infants, tissue Doppler loops should be acquired at frame rates above 180 per s. Myocardial deformation analysis of preterm infants should be performed using a CD of 6 mm, whereas a CD of 10 mm is more reproducible in term infants.

[Isolation,culture and identification of adipose-derived stem cells from SD rat adipose tissues subjected to long-term cryopreservation].

PubMed

Liu, Qin; Wang, Liping; Chen, Fang; Zhang, Yi

2017-02-01

To study the feasibility of isolation and culture of adipose-derived stem cells( ADSCs) from SD rat adipose tissues subjected to long-term cryopreservation. We took inguinal fat pads from healthy SD rats. Adipose tissues were stored with 100 m L / L dimethyl sulfoxide( DMSO) combined with 900 m L / L fetal bovine serum( FBS) in liquid nitrogen. Three months later,the adipose tissues were resuscitated for the isolation and culture of ADSCs. The growth status and morphology were observed. The growth curve and cell surface markers CD29,CD45,CD90 of the 3rd passage cells were analyzed respectively by CCK-8 assay and immunocytochemistry. The 3rd passage cells were induced towards adipogenic lineages and osteogenic lineages by different inducers,and the resulting cells were examined separately by oil red O staining and alizarin red staining. The ADSCs obtained from SD rat adipose tissues subjected to long-term cryopreservation showed a spindle-shape appearance and had a good proliferation ability. The cell growth curve was typical "S " curve.Immunocytochemistry showed that the 3rd passage cells were positive for CD29 and CD90,while negative for CD45. The cells were positive for oil red O staining after adipogenic induction,and also positive for alizarin red staining after osteogenic induction. The ADSCs can be isolated from SD rat adipose tissues subjected to long-term cryopreservation.

Short-term azithromycin treatment promotes cornea allograft survival in the rat.

PubMed

Wacker, Katrin; Denker, Sophy; Hildebrand, Antonia; Eberwein, Philipp; Reinhard, Thomas; Schwartzkopff, Johannes

2013-01-01

Any inflammatory response following corneal transplantation may induce rejection and irreversible graft failure. The purpose of this study is to analyze the anti-inflammatory effect of azithromycin (AZM) following experimental keratoplasty in rats. Corneal transplants were performed between Fisher-donor and Lewis-recipient rats. Recipients were postoperatively treated three times daily with AZM, miglyol, ofloxacin or dexamethasone eye drops. As an additional control, AZM was applied following syngeneic keratoplasty. Furthermore, short-term treatments with AZM for seven days perioperatively or with AZM only three days prior to the transplantation were compared to appropriate controls. All transplants were monitored clinically for opacity, edema, and vascularization. Infiltrating CD45(+), CD4(+), CD8(+), CD25(+), CD161(+) and CD163(+) cells were quantified via immunohistochemistry. AZM significantly promoted corneal graft survival compared with miglyol or ofloxacin treatment. This effect was comparable to topical dexamethasone. No adverse AZM effect was observed. Histology confirmed a significant reduction of infiltrating leukocytes. The short-term application of AZM for three days prior to transplantation or for seven days perioperatively reduced corneal graft rejection significantly compared with the controls. Along with antibiotic properties, topical AZM has a strong anti-inflammatory effect. Following keratoplasty, this effect is comparable to topical dexamethasone without the risk of steroid-induced adverse effects. Short-term treatment with AZM three days prior to the transplantation was sufficient to promote graft survival in the rat keratoplasty model. We therefore suggest further assessing the anti-inflammatory function of topical AZM following keratoplasty in humans.

The Wiggle Index: An Open Source Bioassay to Assess Sub-Lethal Insecticide Response in Drosophila melanogaster

PubMed Central

Denecke, Shane; Nowell, Cameron J.; Fournier-Level, Alexandre; Perry, Trent; Batterham, Phil

2015-01-01

Toxicological assays measuring mortality are routinely used to describe insecticide response, but sub-lethal exposures to insecticides can select for resistance and yield additional biological information describing the ways in which an insecticide impacts the insect. Here we present the Wiggle Index (WI), a high-throughput method to quantify insecticide response by measuring the reduction in motility during sub-lethal exposures in larvae of the vinegar fly Drosophila melanogaster. A susceptible wild type strain was exposed to the insecticides chlorantraniliprole, imidacloprid, spinosad, and ivermectin. Each insecticide reduced larval motility, but response times and profiles differed among insecticides. Two sets of target site mutants previously identified in mortality studies on the basis of imidacloprid or spinosad resistance phenotypes were tested. In each case the resistant mutant responded significantly less than the control. The WI was also able to detect a spinosad response in the absence of the primary spinosad target site. This response was not detected in mortality assays suggesting that spinosad, like many other insecticides, may have secondary targets affecting behaviour. The ability of the WI to detect changes in insecticide metabolism was confirmed by overexpressing the imidacloprid metabolizing Cyp6g1 gene in digestive tissues or the central nervous system. The data presented here validate the WI as an inexpensive, generic, sub-lethal assay that can complement information gained from mortality assays, extending our understanding of the genetic basis of insecticide response in D. melanogaster. PMID:26684454

Performance of honey bee colonies under a long-lasting dietary exposure to sublethal concentrations of the neonicotinoid insecticide thiacloprid.

PubMed

Siede, Reinhold; Faust, Lena; Meixner, Marina D; Maus, Christian; Grünewald, Bernd; Büchler, Ralph

2017-07-01

Substantial honey bee colony losses have occurred periodically in the last decades. The drivers for these losses are not fully understood. The influence of pests and pathogens are beyond dispute, but in addition, chronic exposure to sublethal concentrations of pesticides has been suggested to affect the performance of honey bee colonies. This study aims to elucidate the potential effects of a chronic exposure to sublethal concentrations (one realistic worst-case concentration) of the neonicotinoid thiacloprid to honey bee colonies in a three year replicated colony feeding study. Thiacloprid did not significantly affect the colony strength. No differences between treatment and control were observed for the mortality of bees, the infestation with the parasitic mite Varroa destructor and the infection levels of viruses. No colony losses occurred during the overwintering seasons. Furthermore, thiacloprid did not influence the constitutive expression of the immunity-related hymenoptaecin gene. However, upregulation of hymenoptaecin expression as a response to bacterial challenge was less pronounced in exposed bees than in control bees. Under field conditions, bee colonies are not adversely affected by a long-lasting exposure to sublethal concentrations of thiacloprid. No indications were found that field-realistic and higher doses exerted a biologically significant effect on colony performance. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Toxic and hormetic-like effects of three components of citrus essential oils on adult Mediterranean fruit flies (Ceratitis capitata)

PubMed Central

Papanastasiou, Stella A.; Bali, Eleftheria-Maria D.; Ioannou, Charalampos S.; Papachristos, Dimitrios P.; Zarpas, Kostas D.

2017-01-01

Plant essential oils (EOs) and a wide range of their individual components are involved in a variety of biological interactions with insect pests including stimulatory, deterrent, toxic and even hormetic effects. Both the beneficial and toxic properties of citrus EOs on the Mediterranean fruit fly (medfly) have been experimentally evidenced over the last years. However, no information is available regarding the toxic or beneficial effects of the major components of citrus EOs via contact with the adults of the Mediterranean fruit fly. In the present study, we explored the toxicity of limonene, linalool and α-pinene (3 of the main compounds of citrus EOs) against adult medflies and identified the effects of sub-lethal doses of limonene on fitness traits in a relaxed [full diet (yeast and sugar)] and in a stressful (sugar only) feeding environment. Our results demonstrate that all three compounds inferred high toxicity to adult medflies regardless of the diet, with males being more sensitive than females. Sub-lethal doses of limonene (LD20) enhanced the lifespan of adult medflies when they were deprived of protein. Fecundity was positively affected when females were exposed to limonene sub-lethal doses. Therefore, limonene, a major constituent of citrus EOs, induces high mortality at increased doses and positive effects on life history traits of medfly adults through contact at low sub-lethal doses. A hormetic-like effect of limonene to adult medflies and its possible underlying mechanisms are discussed. PMID:28520791

Influence of Lactobacillus plantarum WCFS1 on post-acidification, metabolite formation and survival of starter bacteria in set-yoghurt.

PubMed

Settachaimongkon, Sarn; van Valenberg, Hein J F; Gazi, Inge; Nout, M J Robert; van Hooijdonk, Toon C M; Zwietering, Marcel H; Smid, Eddy J

2016-10-01

The objectives of this study were to evaluate the growth and survival of the model probiotic strain Lactobacillus plantarum WCFS1 in co-culture with traditional yoghurt starters and to investigate the impact of preculturing on their survival and metabolite formation in set-yoghurt. L. plantarum WCFS1 was precultured under sublethal stress conditions (combinations of elevated NaCl and low pH) in a batch fermentor before inoculation in milk. Adaptive responses of L. plantarum WCFS1 were evaluated by monitoring bacterial population dynamics, milk acidification and changes in volatile and non-volatile metabolite profiles of set-yoghurt. The results demonstrated that sublethal preculturing did not significantly affect survival of L. plantarum WCFS1. On the other hand, incorporation of sublethally precultured L. plantarum WCFS1 significantly impaired the survival of Lactobacillus delbrueckii subsp. bulgaricus which consequently reduced the post-acidification of yoghurt during refrigerated storage. A complementary metabolomics approach using headspace SPME-GC/MS and (1)H NMR combined with multivariate statistical analysis revealed substantial impact of sublethally precultured L. plantarum WCFS1 on the metabolite profiles of set-yoghurt. This study provides insight in the technological implications of non-dairy model probiotic strain L. plantarum WCFS1, such as its good stability in fermented milk and the inhibitory effect on post-acidification. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sub-Lethal Dose of Shiga Toxin 2 from Enterohemorrhagic Escherichia coli Affects Balance and Cerebellar Cytoarchitecture

PubMed Central

Pinto, Alipio; Cangelosi, Adriana; Geoghegan, Patricia A.; Tironi-Farinati, Carla; Brener, Gabriela J.; Goldstein, Jorge

2016-01-01

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 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 1 ηg 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. PMID:26904009

Influence of sub-lethal stresses on the survival of lactic acid bacteria after spray-drying in orange juice.

PubMed

Barbosa, J; Borges, S; Teixeira, P

2015-12-01

The demand for new functional non-dairy based products makes the production of a probiotic orange juice powder an encouraging challenge. However, during drying process and storage, loss of viability of the dried probiotic cultures can occur, since the cells are exposed to various stresses. The influence of sub-lethal conditions of temperature, acidic pH and hydrogen peroxide on the viability of Pediococcus acidilactici HA-6111-2 and Lactobacillus plantarum 299v during spray drying in orange juice and subsequent storage under different conditions was investigated. At the end of storage, the survival of both microorganisms through simulated gastro-intestinal tract (GIT) conditions was also determined. The viability of cells previously exposed to each stress was not affected by the drying process. However, during 180 days of storage at room temperature, unlike P. acidilactici HA-6111-2, survival of L. plantarum 299v was enhanced by prior exposure to sub-lethal conditions. Previous exposure to sub-lethal stresses of each microorganism did not improve their viability after passage through simulated GIT. Nevertheless, as cellular inactivation during 180 days of storage was low, both microorganisms were present in numbers of ca. 10(7) cfu/mL at the end of GIT. This is an indication that both bacteria are good candidates for use in the development of an orange juice powder with functional characteristics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Lethal and sub-lethal effects of cyproconazole on freshwater organisms: a case study with Chironomus riparius and Dugesia tigrina.

PubMed

Saraiva, Althiéris S; Sarmento, Renato A; Golovko, Oksana; Randak, Tomas; Pestana, João L T; Soares, Amadeu M V M

2018-04-01

The fungicide cyproconazole (CPZ) inhibits the biosynthesis of ergosterol, an essential sterol component in fungal cell membrane and can also affect non-target organisms by its inhibitory effects on P450 monooxygenases. The predicted environmental concentration of CPZ is up to 49.05 μg/L and 145.89 μg/kg in surface waters and sediments, respectively, and information about CPZ toxicity towards non-target aquatic organisms is still limited. This study aimed to address the lack of ecotoxicological data for CPZ, and thus, an evaluation of the lethal and sub-lethal effects of CPZ was performed using two freshwater invertebrates (the midge Chironomus riparius and the planarian Dugesia tigrina). The estimated CPZ 48 h LC 50 (95% CI) was 17.46 mg/L for C. riparius and 47.38 mg/L for D. tigrina. The emergence time (EmT 50 ) of C. riparius was delayed by CPZ exposure from 0.76 mg/L. On the other hand, planarians showed higher tolerance to CPZ exposure. Sub-lethal effects of CPZ on planarians included reductions in locomotion (1.8 mg/L), delayed photoreceptors regeneration (from 0.45 mg/L), and feeding inhibition (5.6 mg/L). Our results confirm the moderate toxicity of CPZ towards aquatic invertebrates but sub-lethal effects observed also suggest potential chronic effects of CPZ with consequences for population dynamics.

Metabolic Response of Escherichia coli upon Treatment with Hypochlorite at Sub-Lethal Concentrations

PubMed Central

Winter, Jeannette; Eisenreich, Wolfgang

2015-01-01

Hypochlorite is a reactive oxygen species that is worldwide as an antibacterial disinfectant. Hypochlorite exposure is known to cause oxidative damage to DNA and proteins. As a response to these effects, the metabolite profiles of organisms treated with sub-lethal doses of hypochlorite are assumed to be severely modified; however, the nature of these changes is hardly understood. Therefore, using nuclear magnetic resonance spectroscopy and gas chromatography-coupled mass spectrometry, we analyzed the time-dependent impact of hypochlorite exposure with a sub-lethal concentration (50 µM) on the metabolite profile of the Escherichia coli strain MG1655. Principle component analysis clearly distinguished between the metabolite profiles of bacteria treated for 0, 5,10, 20, 40, or 60 min. Major changes in the relative amounts of fatty acids, acetic acid, and formic acid occurred within the first 5 min. Comparative gas chromatography-coupled mass spectrometry analyses revealed that the amounts of free methionine and alanine were significantly decreased in the treated cells, demonstrating their susceptibility to hypochlorite exposure. The concentrations of succinate, urea, orotic acid, 2-aminobutyric acid, and 2-hydroxybutyric acid were also severely affected, indicating general changes in the metabolic network by hypochlorite. However, most metabolite levels relaxed to the reference values of untreated cells after 40–60 min, reflecting the capability of E. coli to rapidly adapt to environmental stress factors such as the presence of sub-lethal oxidant levels. PMID:25932918

Major role of the PI3K/Akt pathway in ischemic tolerance induced by sublethal oxygen-glucose deprivation in cortical neurons in vitro.

PubMed

Bhuiyan, Mohammad Iqbal Hossain; Jung, Seo Yun; Kim, Hyoung Ja; Lee, Yong Sup; Jin, Changbae

2011-06-01

Ischemic preconditioning can provide protection to neurons from subsequent lethal ischemia. The molecular mechanisms of neuronal ischemic tolerance, however, are still not well-known. The present study, therefore, examined the role of MAPK and PI3K/Akt pathways in ischemic tolerance induced by preconditioning with sublethal oxygen-glucose deprivation (OGD) in cultured rat cortical neurons. Ischemic tolerance was simulated by preconditioning of the neurons with sublethal 1-h OGD imposed 12 h before lethal 3-h OGD. The time-course studies of relative phosphorylation and expression levels of ERK1/2, JNK and p38 MAPK showed lack of their involvement in ischemic tolerance. However, there were significant increases in Akt phosphorylation levels during the reperfusion period following preconditioned lethal OGD. In addition, Bcl-2 associated death promoter (Bad) and GSK-3β were also found to be inactivated during that reperfusion period. Finally, treatment with an inhibitor of PI3K, wortmannin, applied from 15 min before and during lethal OGD abolished not only the preconditioning-induced neuroprotection but also the Akt activation. Concomitant with blockade of the Akt activation, PI3K inhibition also resulted in activation of Bad and GSK-3β. The results suggest that ischemic tolerance induced by sublethal OGD preconditioning is primarily mediated through activation of the PI3K/Akt pathway, but not the MAPK pathway, in rat cortical neurons.

Fumigant Toxicity and Sublethal Effects of Artemisia khorassanica and Artemisia sieberi on Sitotroga cerealella (Lepidoptera: Gelechiidae).

PubMed

Naseri, B; Abedi, Z; Abdolmaleki, A; Jafary-Jahed, M; Borzoui, E; Mozaffar Mansouri, Seyed

2017-09-01

Fumigant toxicity and sublethal effects of essential oils from Artemisia khorassanica Podl. and Artemisia sieberi Bess were investigated against adults of Sitotroga cerealella Olivier. To assess the sublethal effects, adult moths were exposed to the LC30 of each essential oil, and life table parameters of the surviving S. cerealella were studied. Higher fumigant toxicity of A. khorassanica (LC50: 7.38 µl/liter air) than A. sieberi (LC50: 9.26 µl/liter air) was observed against S. cerealella. Also, the insecticidal effects of A. khorassanica (LT50: 9.01 h) were faster than A. sieberi (LT50: 14.37 h). A significant extension was observed in the developmental time (egg to adult) of S. cerealella treated with the essential oils. In addition, fecundity of S. cerealella reduced by 25.29 and 35.78% following exposure to sublethal concentrations of A. sieberi and A. khorassanica, respectively. Both tested essential oils caused a significant reduction in the gross and net reproductive rates, intrinsic rate of increase (rm), and finite rate of increase of S. cerealella. The rm values following exposure to A. sieberi, A. khorassanica, and control were 0.098, 0.094, and 0.107 d-1, respectively. The results of this study suggest that tested essential oils have a good potential to apply in integrated pest management of S. cerealella. © The Author 2017. Published by Oxford University Press on behalf of Entomological Society of America.

Splenectomy Fails to Provide Long-Term Protection Against Ischemic Stroke.

PubMed

Ran, Yuanyuan; Liu, Zongjian; Huang, Shuo; Shen, Jiamei; Li, Fengwu; Zhang, Wenxiu; Chen, Chen; Geng, Xiaokun; Ji, Zhili; Du, Huishan; Hu, Xiaoming

2018-06-01

Splenectomy before or immediately after stroke provides early brain protection. This study aims to explore the effect of splenectomy on long-term neurological recovery after stroke, which is currently lacking in the field. Adult male rats were randomized into splenectomy or sham groups and then subjected to 90 min of middle cerebral artery occlusion (MCAO). Spleen was removed right upon reperfusion or 3d after MCAO. Infarct volume, neurological functions, and peripheral immune cell populations were assessed up to 28d after stroke. The results show that delayed removal of spleen did not reduce brain tissue loss and showed no effect on sensorimotor function (Rotarod, beam balance, forelimb placing, grid walk, and adhesive removal tests) or cognitive function (Morris water maze). Spleen removal immediately upon reperfusion, although significantly reduced the infarct size and immune cell infiltration 3d after MCAO, also failed to promote long-term recovery. Flow cytometry analysis demonstrated that immediate splenectomy after MCAO resulted in a prolonged decrease in the percentage of CD3 + CD4 + and CD3 + CD8 + T cells in total lymphocytes as compared to non-splenectomy MCAO rats. In contrast, the percentage of CD3 - CD45RA + B cells was significantly elevated after splenectomy. As a result, the ratio of T/B cells was significantly reduced in stroke rats with splenectomy. In conclusion, delayed splenectomy failed to provide long-term protection to the ischemic brain or improve functional recovery. The acute neuroprotective effect achieved by early splenectomy after stroke cannot last for long term. This loss of neuroprotection might be related to the prolonged disturbance in the T cell to B cell ratio.

Down-regulation of FcεRI-mediated CD63 basophil response during short-term VIT determined venom-nonspecific desensitization.

PubMed

Čelesnik Smodiš, Nina; Šilar, Mira; Eržen, Renato; Rijavec, Matija; Košnik, Mitja; Korošec, Peter

2014-01-01

We recently showed a desensitization of FcεRI-mediated basophil response after short-term VIT. Our aim was to evaluate the allergen specificity of this desensitization. In 11 Hymenoptera-venom double positive subjects, basophil threshold sensitivity (CD-sens) to anti-FcεRI, honeybee, and Vespula venom was assessed at the beginning and just before the first maintenance dose (MD) of single ultra-rush VIT. In some patients we also monitored CD-sens to rApi m 1 and/or rVes v 5 or other co-sensitizations (i.e., grass pollen). In additional 7 patients, basophils were stripped and sensitized with house dust mite (HDM) IgEs at the same time points. We demonstrated a marked reduction of CD-sens to anti-FcεRI and VIT-specific venom before the first MD in all 18 subjects included. Furthermore, in 10 out of 11 double positive subjects, a significant and comparable decrease before the first MD was also evident for non-VIT venom; this nonspecific decrease was further supported by the opposite recombinant species-specific major allergen. In one subject with additional grass pollen allergy, a decrease of CD-sens to grass allergen was also demonstrated. Similarly, in 7 cases of patients with passively HDM-sensitized basophils, a significant reduction of CD-sens was also evident to de novo sensitized HDM allergen. Short-term VIT induced basophil desensitization to VIT-specific as well as to VIT-nonspecific venom. As opposed to long-term VIT, which induces venom-specific changes, the effect of short-term VIT seems to be venom-nonspecific.

Down-Regulation of FcεRI-Mediated CD63 Basophil Response during Short-Term VIT Determined Venom-Nonspecific Desensitization

PubMed Central

Čelesnik Smodiš, Nina; Šilar, Mira; Eržen, Renato; Rijavec, Matija; Košnik, Mitja; Korošec, Peter

2014-01-01

Background We recently showed a desensitization of FcεRI-mediated basophil response after short-term VIT. Our aim was to evaluate the allergen specificity of this desensitization. Methods In 11 Hymenoptera-venom double positive subjects, basophil threshold sensitivity (CD-sens) to anti-FcεRI, honeybee, and Vespula venom was assessed at the beginning and just before the first maintenance dose (MD) of single ultra-rush VIT. In some patients we also monitored CD-sens to rApi m 1 and/or rVes v 5 or other co-sensitizations (i.e., grass pollen). In additional 7 patients, basophils were stripped and sensitized with house dust mite (HDM) IgEs at the same time points. Results We demonstrated a marked reduction of CD-sens to anti-FcεRI and VIT-specific venom before the first MD in all 18 subjects included. Furthermore, in 10 out of 11 double positive subjects, a significant and comparable decrease before the first MD was also evident for non-VIT venom; this nonspecific decrease was further supported by the opposite recombinant species-specific major allergen. In one subject with additional grass pollen allergy, a decrease of CD-sens to grass allergen was also demonstrated. Similarly, in 7 cases of patients with passively HDM-sensitized basophils, a significant reduction of CD-sens was also evident to de novo sensitized HDM allergen. Conclusions Short-term VIT induced basophil desensitization to VIT-specific as well as to VIT-nonspecific venom. As opposed to long-term VIT, which induces venom-specific changes, the effect of short-term VIT seems to be venom-nonspecific. PMID:24733549

Long-Term Effects of Highly Active Antiretroviral Therapy on CD4+ Cell Evolution among Children and Adolescents Infected with HIV: 5 Years and Counting

PubMed Central

Patel, Kunjal; Hernán, Miguel A.; Williams, Paige L.; Seeger, John D.; McIntosh, Kenneth; Van Dyke, Russell B.; Seage, George R.

2011-01-01

Background Lower percentages of CD4+ T lymphocytes are associated with adverse clinical outcomes among children and adolescents infected with human immunodeficiency virus (HIV). CD4+ lymphocyte percentage generally increases with receipt of highly active antiretroviral therapy (HAART), but long-term follow-up is required to assess whether these increases in CD4+ cell percentage are maintained and whether they lead to normal CD4+ cell percentages in children with severe immunosuppression. Methods The study population included 1236 children and adolescents perinatally infected with HIV who were enrolled in a US-based multicenter prospective cohort study (Pediatric AIDS Clinical Trials Group 219/219C) and who were not receiving HAART at study initiation. We estimated the effects of HAART, HAART with protease inhibitors, and HAART with nonnucleoside reverse-transcriptase inhibitors on CD4+ cell percentage, using marginal structural models to account for confounding by severity. Results Initiation of any type of HAART increased CD4+ cell percentage by 2.34% (95% confidence interval, 1.35%–3.33%) in the first year, relative to noninitiation of HAART. The substantial increases in CD4+ cell percentage observed after the first year of experience with these combination therapies were followed by relatively smaller increases that continued for 5 years after initiation. Although larger increases in CD4+ cell percentage were observed among children with a greater degree of immunosuppression at baseline, the mean CD4+ cell percentage after 5 years of HAART did not reach normal levels. Conclusions Our study supports the initiation of HAART in children before severe immunosuppression occurs for long-term maintenance of normal CD4+ cell percentages. This beneficial result must be weighed against the evidence of potential adverse events associated with the prolonged use of such therapy. PMID:18426371

Phenotype and specificity of T cells in primary human cytomegalovirus infection during pregnancy: IL-7Rpos long-term memory phenotype is associated with protection from vertical transmission.

PubMed

Mele, Federico; Fornara, Chiara; Jarrossay, David; Furione, Milena; Arossa, Alessia; Spinillo, Arsenio; Lanzavecchia, Antonio; Gerna, Giuseppe; Sallusto, Federica; Lilleri, Daniele

2017-01-01

Congenital human cytomegalovirus (HCMV) infection is the major cause of birth defects and a precise definition of the HCMV-specific T-cell response in primary infection may help define reliable correlates of immune protection during pregnancy. In this study, a high throughput method was used to define the frequency of CD4+ and CD8+ T cells specific for four HCMV proteins in the naïve compartment of seronegative subjects and the effector/memory compartments of subjects with primary/remote HCMV infection. The naïve repertoire displayed comparable frequencies of T cells that were reactive with HCMV structural (pp65, gB and the pentamer gHgLpUL128L) and non-structural (IE-1) proteins. Whereas, following natural infection, the majority of effector/memory CD4+ and CD8+ T cells recognized either gB or IE-1, respectively, and pp65. The pattern of T cell reactivity was comparable at early and late stages of infection and in pregnant women with primary HCMV infection transmitting or not transmitting the virus to the fetus. At an early stage of primary infection, about 50% of HCMV-reactive CD4+ T cells were long-term IL-7Rpos memory cells, while 6-12 months later, the frequency of these cells increased to 70%, approaching 100% in remote infections. In contrast, only 10-20% of HCMV-specific CD8+ T cells were long-term memory cells up to 12 months after infection onset, thereafter increasing to 70% in remote infections. Interestingly, a significantly higher frequency of HCMV-specific CD4+ T cells with a long-term IL-7Rpos memory phenotype was observed in non-transmitting compared to transmitting women. These findings indicate that immunodominance in HCMV infection is not predetermined in the naïve compartment, but is the result of virus-host interactions and suggest that prompt control of HCMV infection in pregnancy is associated with the rapid development of long-term IL-7Rpos memory HCMV-specific CD4+ T cells and a low risk of virus transmission to the fetus.

Vedolizumab Induces Long-term Mucosal Healing in Patients With Crohn's Disease and Ulcerative Colitis.

PubMed

Noman, Maja; Ferrante, Marc; Bisschops, Raf; De Hertogh, Gert; Van den Broeck, Karolien; Rans, Karen; Rutgeerts, Paul; Vermeire, Séverine; Van Assche, Gert

2017-09-01

Vedolizumab has proven efficacy in inflammatory bowel disease [IBD], but long-term mucosal healing in Crohn's disease [CD], as well as the incidence of colorectal neoplasia in IBD, among patients treated with vedolizumab have not been studied. We aimed to document mucosal healing and to explore the risk of colorectal neoplasia with vedolizumab maintenance therapy. Surveillance colonoscopy was prospectively scheduled for patients with longstanding ulcerative coltis [UC] or CD at a tertiary referral centre, in the open-label extension phase (vedolizumab 300 mg intravenously [IV] every 4 weeks) of the Gemini studies [GEMINI LTS, study number NCT00790933]. Mayo score ≤ 1 or ulcer disappearance [in CD] was defined as mucosal healing. Targeted biopsies were graded for inflammation and dysplasia. Of 68 patients [29 CD/39 UC] treated for ≥ 1 year [median 3.2 years, range 1.1-6.1], 58 [24 CD/34 UC] were endoscopically monitored. Durable endoscopic healing corrected by non-responder imputation was found in 7/24, 29% [CD] and 17/34, 50% [UC]. Combined histological and mucosal healing was observed in 5/24 [CD] and 11/34 [UC] of those with endoscopic healing. Low-grade dysplasia was detected in 10% of patients and high-grade dysplasia in the resection specimen of one patient with biopsy-proven low-grade dysplasia. Long-term endoscopic and histological healing was observed in a proportion of patients treated with vedolizumab long-term. The dysplasia risk with vedolizumab deserves further study. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

Cisplatin selects for stem-like cells in osteosarcoma by activating Notch signaling

PubMed Central

Yang, Jian; Gao, Tian; Simões, Bruno M.; Eyre, Rachel; Guo, Weichun; Clarke, Robert B.

2016-01-01

Notch signaling regulates normal stem cells and is also thought to regulate cancer stem cells (CSCs). Recent data indicate that Notch signaling plays a role in the development and progression of osteosarcoma, however the regulation of Notch in chemo-resistant stem-like cells has not yet been fully elucidated. In this study we generated cisplatin-resistant osteosarcoma cells by treating them with sub-lethal dose of cisplatin, sufficient to induce DNA damage responses. Cisplatin-resistant osteosarcoma cells exhibited lower proliferation, enhanced spheroid formation and more mesenchymal characteristics than cisplatin-sensitive cells, were enriched for Stro-1+/CD117+ cells and showed increased expression of stem cell-related genes. A similar effect was observed in vivo, and in addition in vivo tumorigenicity was enhanced during serial transplantation. Using several publicly available datasets, we identified that Notch expression was closely associated with osteosarcoma stem cells and chemotherapy resistance. We confirmed that cisplatin-induced enrichment of osteosarcoma stem cells was mediated through Notch signaling in vitro, and immunohistochemistry showed that cleaved Notch1 (NICD1) positive cells were significantly increased in a relapsed xenograft which had received cisplatin treatment. Furthermore, pretreatment with a γ-secretase inhibitor (GSI) to prevent Notch signalling inhibited cisplatin-enriched osteosarcoma stem cell activity in vitro, including Stro-1+/CD117+ double positive cells and spheroid formation capacity. The Notch inhibitor DAPT also prevented tumor recurrence in resistant xenograft tumors. Overall, our results show that cisplatin induces the enrichment of osteosarcoma stem-like cells through Notch signaling, and targeted inactivation of Notch may be useful for the elimination of CSCs and overcoming drug resistance. PMID:27102300

Radiation combined with thermal injury induces immature myeloid cells.

PubMed

Mendoza, April Elizabeth; Neely, Crystal Judith; Charles, Anthony G; Kartchner, Laurel Briane; Brickey, Willie June; Khoury, Amal Lina; Sempowski, Gregory D; Ting, Jenny P Y; Cairns, Bruce A; Maile, Robert

2012-11-01

The continued development of nuclear weapons and the potential for thermonuclear injury necessitates the further understanding of the immune consequences after radiation combined with injury (RCI). We hypothesized that sublethal ionization radiation exposure combined with a full-thickness thermal injury would result in the production of immature myeloid cells. Mice underwent either a full-thickness contact burn of 20% total body surface area or sham procedure followed by a single whole-body dose of 5-Gy radiation. Serum, spleen, and peripheral lymph nodes were harvested at 3 and 14 days after injury. Flow cytometry was performed to identify and characterize adaptive and innate cell compartments. Elevated proinflammatory and anti-inflammatory serum cytokines and profound leukopenia were observed after RCI. A population of cells with dual expression of the cell surface markers Gr-1 and CD11b were identified in all experimental groups, but were significantly elevated after burn alone and RCI at 14 days after injury. In contrast to the T-cell-suppressive nature of myeloid-derived suppressor cells found after trauma and sepsis, myeloid cells after RCI augmented T-cell proliferation and were associated with a weak but significant increase in interferon γ and a decrease in interleukin 10. This is consistent with previous work in burn injury indicating that a myeloid-derived suppressor cell-like population increases innate immunity. Radiation combined injury results in the increase in distinct populations of Gr-1CD11b cells within the secondary lymphoid organs, and we propose these immature inflammatory myeloid cells provide innate immunity to the severely injured and immunocompromised host.

Innovative 'Artificial Mussels' technology for assessing spatial and temporal distribution of metals in Goulburn-Murray catchments waterways, Victoria, Australia: effects of climate variability (dry vs. wet years).

PubMed

Kibria, Golam; Lau, T C; Wu, Rudolf

2012-12-01

The "Artificial mussel" (AM), a novel passive sampling technology, was used for the first time in Australia in freshwater to monitor and assess the risk of trace metals (Cd, Cu, Hg, Pb, and Zn). AMs were deployed at 10 sites within the Goulburn-Murray Water catchments, Victoria, Australia during a dry year (2009-2010) and a wet year (2010-2011). Our results showed that the AMs accumulated all the five metals. Cd, Pb, Hg were detected during the wet year but below detection limits during the dry year. At some sites close to orchards, vine yards and farming areas, elevated levels of Cu were clearly evident during the dry year, while elevated levels of Zn were found during the wet year; the Cu indicates localized inputs from the agricultural application of copper fungicide. The impacts from old mines were significantly less compared 'hot spots'. Our study demonstrated that climate variability (dry, wet years) can influence the metal inputs to waterways via different transport pathways. Using the AMs, we were able to identify various 'hot spots' of heavy metals, which may pose a potential risk to aquatic ecosystems (sub-lethal effects to fish) and public (via food chain metal bioaccumulation and biomagnification) in the Goulburn-Murray Water catchments. The State Protection Policy exempted artificial channels and drains from protection of beneficial use (including protection of aquatic ecosystems) and majority of sites ('hot spots') were located within artificial irrigation channels. Copyright © 2012 Elsevier Ltd. All rights reserved.

Using organic-certified rather than synthetic pesticides may not be safer for biological control agents: selectivity and side effects of 14 pesticides on the predator Orius laevigatus.

PubMed

Biondi, Antonio; Desneux, Nicolas; Siscaro, Gaetano; Zappalà, Lucia

2012-05-01

The generalist predator Orius laevigatus (Fieber) (Hemiptera: Anthocoridae) is a key natural enemy of various arthropods in agricultural and natural ecosystems. Releases of this predator are frequently carried out, and it is included in the Integrated Pest Management (IPM) programs of several crops. The accurate assessment of the compatibility of various pesticides with predator activity is key for the success of this strategy. We assessed acute and sublethal toxicity of 14 pesticides on O. laevigatus adults under laboratory conditions. Pesticides commonly used in either conventional or organic farming were selected for the study, including six biopesticides, three synthetic insecticides, two sulfur compounds and three adjuvants. To assess the pesticides' residual persistence, the predator was exposed for 3d to pesticide residues on tomato sprouts that had been treated 1 h, 7 d or 14 d prior to the assay. The percentage of mortality and the sublethal effects on predator reproductive capacity were summarized in a reduction coefficient (E(x)) and the pesticides were classified according to the IOBC (International Organization for Biological Control) toxicity categories. The results showed that the pesticides greatly differed in their toxicity, both in terms of lethal and sub lethal effects, as well as in their persistence. In particular, abamectin was the most noxious and persistent, and was classified as harmful up to 14 d after the treatment, causing almost 100% mortality. Spinosad, emamectin, metaflumizone were moderately harmful until 7 d after the treatment, while the other pesticides were slightly harmful or harmless. The results, based on the combination of assessment of acute mortality, predator reproductive capacity pesticides residual and pesticides residual persistence, stress the need of using complementary bioassays (e.g. assessment of lethal and sublethal effects) to carefully select the pesticides to be used in IPM programs and appropriately time the pesticides application (as function of natural enemies present in crops) and potential releases of natural enemies like O. laevigatus. Copyright © 2012 Elsevier Ltd. All rights reserved.

Gemcitabine enhances cell invasion via activating HAb18G/CD147-EGFR-pSTAT3 signaling.

PubMed

Xu, Bao-Qing; Fu, Zhi-Guang; Meng, Yao; Wu, Xiao-Qing; Wu, Bo; Xu, Liang; Jiang, Jian-Li; Li, Ling; Chen, Zhi-Nan

2016-09-20

Pancreatic cancer, one of the most lethal cancers, has very poor 5-year survival partly due to gemcitabine resistance. Recently, it was reported that chemotherapeutic agents may act as stressors to induce adaptive responses and to promote chemoresistance in cancer cells. During long-term drug treatment, the minority of cancer cells survive and acquire an epithelial-mesenchymal transition phenotype with increased chemo-resistance and metastasis. However, the short-term response of most cancer cells remains unclear. This study aimed to investigate the short-term response of pancreatic cancer cells to gemcitabine stress and to explore the corresponding mechanism. Our results showed that gemcitabine treatment for 24 hours enhanced pancreatic cancer cell invasion. In gemcitabine-treated cells, HAb18G/CD147 was up-regulated; and HAb18G/CD147 down-regulation or inhibition attenuated gemcitabine-enhanced invasion. Mechanistically, HAb18G/CD147 promoted gemcitabine-enhanced invasion by activating the EGFR (epidermal growth factor receptor)-STAT3 (signal transducer and activator of transcription 3) signaling pathway. Inhibition of EGFR-STAT3 signaling counteracted gemcitabine-enhanced invasion, and which relied on HAb18G/CD147 levels. In pancreatic cancer tissues, EGFR was highly expressed and positively correlated with HAb18G/CD147. These data indicate that pancreatic cancer cells enhance cell invasion via activating HAb18G/CD147-EGFR-pSTAT3 signaling. Our findings suggest that inhibiting HAb18G/CD147 is a potential strategy for overcoming drug stress-associated resistance in pancreatic cancer.

Effects of salinity on short-term waterborne zinc uptake, accumulation and sub-lethal toxicity in the green shore crab (Carcinus maenas).

PubMed

Niyogi, Som; Blewett, Tamzin A; Gallagher, Trevor; Fehsenfeld, Sandra; Wood, Chris M

2016-09-01

Waterborne zinc (Zn) is known to cause toxicity to freshwater animals primarily by disrupting calcium (Ca) homeostasis during acute exposure, but its effects in marine and estuarine animals are not well characterized. The present study investigated the effects of salinity on short-term Zn accumulation and sub-lethal toxicity in the euryhaline green shore crab, Carcinus maenas. The kinetic and pharmacological properties of short-term branchial Zn uptake were also examined. Green crabs (n=10) were exposed to control (no added Zn) and 50μM (3.25mgL(-1)) of waterborne Zn (∼25% of 96h LC50 in 100 seawater) for 96h at 3 different salinity regimes (100%, 60% and 20% seawater). Exposure to waterborne Zn increased tissue-specific Zn accumulation across different salinities. However, the maximum accumulation occurred in 20% seawater and no difference was recorded between 60% and 100% seawater. Gills appeared to be the primary site of Zn accumulation, since the accumulation was significantly higher in the gills relative to the hepatopancreas, haemolymph and muscle. Waterborne Zn exposure induced a slight increase in haemolymph osmolality and chloride levels irrespective of salinity. In contrast, Zn exposure elicited marked increases in both haemolymph and gill Ca levels, and these changes were more pronounced in 20% seawater relative to that in 60% or 100% seawater. An in vitro gill perfusion technique was used to examine the characteristics of short-term (1-4h) branchial Zn uptake over an exposure concentration range of 3-12μM (200-800μgL(-1)). The rate of short-term branchial Zn uptake did not change significantly after 2h, and no difference was recorded in the rate of uptake between the anterior (respiratory) and posterior (ion transporting) gills. The in vitro branchial Zn uptake occurred in a concentration-dependent manner across different salinities. However, the rate of uptake was consistently higher in 20% seawater relative to 60% or 100% seawater - similar to the trend observed with tissue Zn accumulation during in vivo exposure. The short-term branchial Zn uptake was found to be inhibited by lanthanum (a blocker of voltage-independent Ca channels), suggesting that branchial Zn uptake occurs via the Ca transporting pathways, at least in part. Overall, our findings indicate that acute exposure to waterborne Zn leads to the disruption of Zn and Ca homeostasis in green crab, and these effects are exacerbated at the lower salinity. Copyright © 2016 Elsevier B.V. All rights reserved.

[Influence of pre-transplant serum level of soluble CD30 on the long-term survival rates of kidney transplant recipients and grafts].

PubMed

Chen, Jiang-hua; Lü, Rong; Chen, Ying; Wu, Jian-yong; He, Qiang; Huang, Hong-feng; Qu, Li-hui

2005-06-15

To investigate the influence of pre-transplant sCD30 level on the long-term survival rates of kidney transplant recipients and grafts among Chinese. A retrospective cohort of 707 patients undergoing cadaver renal transplants between Dec.1998 and Aug 2003, 467 males and 240 females, aged 40 +/- 11, with their blood samples preserved was studied. The plasma levels of sCD30 were determined by ELISA. The 5-year graft survival/functional rates of the high sCD30 group were 77.7% +/- 3.5%/85.0% +/- 3.2%, significantly lower than those of the low and intermediate groups, 84.7% +/- 2.1%/98.9% +/- 1.1% and 88.1% +/- 2.9%/95.1% +/- 1.6% respectively (all P < 0.05). The 5-year recipient survival rate of the intermediate sCD30 group was 92.4% +/- 1.6%, higher than those of the low and high sCD30 groups, 84.7% +/- 3.9% and 87.1% +/- 2.7% respectively with a significant difference between the intermediate and high sCD30 groups (P = 0.032). Pre-transplant serum level of sCD30 reflects the immune status. Recipients with high sCD30 are prone to rejection while those with low sCD30 are prone to infections.

Increased peripheral CD4+ regulatory T cells persist after successful direct-acting antiviral treatment of chronic hepatitis C.

PubMed

Langhans, Bettina; Nischalke, Hans Dieter; Krämer, Benjamin; Hausen, Annekristin; Dold, Leona; van Heteren, Peer; Hüneburg, Robert; Nattermann, Jacob; Strassburg, Christian P; Spengler, Ulrich

2017-05-01

CD4 + regulatory T cells (Tregs) expand during chronic hepatitis C virus (HCV) infection, inhibit antiviral immunity and promote fibrosis. Direct-acting antiviral agents (DAA) have revolutionized HCV therapy. However, it is unclear if Tregs are normalized after DAA-induced HCV elimination. We analyzed Tregs before (baseline), at end of therapy (EOT), 12 and 24weeks (SVR12, SVR24) and long-term (51±14weeks) after EOT in 26 genotype-1-infected patients who were successfully treated with sofosbuvir (SOF) plus interferon (IFN)/ribavirin (n=12) and IFN-free DAA regimens (SOF plus daclatasvir or simeprevir; n=14). Frequency, phenotype and suppressor function of peripheral Foxp3 + CD25 + CD4 + T cells were studied by multi-color flow cytometry and co-culture inhibition assays. Frequencies and activation status of Foxp3 + CD25 + CD4 + T cells remained elevated above those of normal controls in both treatment groups even long-term after HCV elimination. Co-culture assays indicated a dose-response relationship for functional inhibition of autologous CD4 + effector T cells and confirmed that activation of Tregs remained largely unchanged over the observation period. Unlike IFN-free regimens, SOF plus IFN/ribavirin induced a transiently increased frequency of Foxp3 + CD25 + CD4 + T cells at EOT (5.0% at baseline to 6.1% at EOT; p=0.001). These Foxp3 + CD25 + CD4 + T cells co-expressed the activation markers glycoprotein A repetitions predominant (GARP; p=0.012) and tumor necrosis factor receptor superfamily, member 4 (OX-40; p=0.001) but showed unchanged in vitro inhibitory activity. Although IFN-based DAA therapy induced transient expansion of activated Foxp3 + CD25 + CD4 + T cells, neither IFN-based nor IFN-free DAA regimens normalized frequencies and activation status of Tregs one year after viral elimination. Persistence of immunosuppressive Tregs may thus contribute to complications of liver disease even long-term after HCV cure. In chronic hepatitis C virus (HCV) infection, CD4 + regulatory T cells (Tregs) can reduce antiviral immune responses, promote liver fibrosis and may increase the risk for liver cancer, because they gradually expand during disease. Modern direct-acting antiviral agents (DAA) can "cure" hepatitis C in almost all treated patients. However, our study shows that DAA do not normalize the increased frequency and activation status of Tregs even long-term after HCV elimination. Tregs may persistently modulate functions of the immune system even after "cure" of hepatitis C. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Effects of Copper Exposure on Photosynthesis and Growth of the Seagrass Cymodocea nodosa: An Experimental Assessment.

PubMed

Llagostera, Izaskun; Cervantes, Daniel; Sanmartí, Neus; Romero, Javier; Pérez, Marta

2016-09-01

Seagrasses form some of the most important coastal habitats. They may be negatively affected by trace metal contamination in certain coastal areas. In this study we experimentally assessed selected morphological and physiological traits of the seagrass Cymodocea nodosa, with increasing concentrations of copper (Cu) under controlled laboratory conditions. Short term (21 days) sub-lethal effects such as decreased maximum quantum yield, increased leaf necrosis and decreased shoot growth and shoot recruitment were clearly observed at the highest Cu exposure (5 mg L(-1)), while the effects were weaker at the intermediate concentration (2.5 mg L(-1)) and almost absent at the lowest concentration (1 mg L(-1)), indicating that this species is highly tolerant to copper exposure, at least in the short term. This fact could help to explain its distribution in relatively polluted coastal waters.

Lung cancer tumorigenicity and drug resistance are maintained through ALDH(hi)CD44(hi) tumor initiating cells.

PubMed

Liu, Jing; Xiao, Zhijie; Wong, Sunny Kit-Man; Tin, Vicky Pui-Chi; Ho, Ka-Yan; Wang, Junwen; Sham, Mai-Har; Wong, Maria Pik

2013-10-01

Limited improvement in long term survival of lung cancer patients has been achieved by conventional chemotherapy or targeted therapy. To explore the potentials of tumor initiating cells (TIC)-directed therapy, it is essential to identify the cell targets and understand their maintenance mechanisms. We have analyzed the performance of ALDH/CD44 co-expression as TIC markers and treatment targets of lung cancer using well-validated in vitro and in vivo analyses in multiple established and patient-derived lung cancer cells. The ALDH(hi)CD44(hi) subset showed the highest enhancement of stem cell phenotypic properties compared to ALDH(hi)CD44(lo), ALDH(lo)CD44(hi), ALDH(lo)CD44(lo) cells and unsorted controls. They showed higher invasion capacities, pluripotency genes and epithelial-mesenchymal transition transcription factors expression, lower intercellular adhesion protein expression and higher G2/M phase cell cycle fraction. In immunosuppressed mice, the ALDH(hi)CD44(hi)xenografts showed the highest tumor induction frequency, serial transplantability, shortest latency, largest volume and highest growth rates. Inhibition of sonic Hedgehog and Notch developmental pathways reduced ALDH+CD44+ compartment. Chemotherapy and targeted therapy resulted in higher AALDH(hi)CD44(hi) subset viability and ALDH(lo)CD44(lo) subset apoptosis fraction. ALDH inhibition and CD44 knockdown led to reduced stemness gene expression and sensitization to drug treatment. In accordance, clinical lung cancers containing a higher abundance of ALDH and CD44-coexpressing cells was associated with lower recurrence-free survival. Together, results suggested theALDH(hi)CD44(hi)compartment was the cellular mediator of tumorigenicity and drug resistance. Further investigation of the regulatory mechanisms underlying ALDH(hi)CD44(hi)TIC maintenance would be beneficial for the development of long term lung cancer control.

Transient CD15-positive endothelial phenotype in the human placenta correlates with physiological and pathological fetoplacental immaturity.

PubMed

Seidmann, L; Suhan, T; Unger, R; Gerein, V; Kirkpatrick, C J

2014-09-01

Placental growth and villous maturation are critical parameters of placental function at the end of pregnancy. A failure in these processes leads to the development of placental dysfunction, as well as fetal and neonatal mortality and morbidity. The aim of the study was to determine the relevant diagnostic markers associated with pathological placental development. Forty tissue samples from normal placentas of different gestational age and 68 pathological term placentas with defective villous maturation (GDM, idiopathic IUFD, preeclamsia, HELLP syndrome) comprised the comparative immunohistochemical study (CD15, CD45 and CD34). Positive immunohistochemical reactions were quantitatively assessed in the chorionic plate and vessels of the villi of different histological type. Physiologically immature placentas of the first and second trimester and pathologically immature term placentas were characterized by marked endothelial CD15-immunostaining. A significant loss of CD15-positive endothelium of the placentas was associated with a physiological and accelerated villous maturity. A spatio-temporal correlation was shown for CD15+ endothelial cells (ECs) and the number of CD45+ stromal cells (SCs). A negative temporal correlation was shown for CD15+ ECs and CD15+ myelomonocytes in the fetal blood. CD34 expression in the ECs was stable during the pregnancy. A correlation between a transient CD15-positive endothelial phenotype and a physiological and pathological fetoplacental immaturity was demonstrated. Physiological and accelerated placental maturation was accompanied by a significant disappearance of CD15-positive endothelium. We propose that "immature" CD15+ endothelium is an important diagnostic marker of the physiological and pathological fetoplacental immaturity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Reduced sCD36 following weight loss corresponds to improved insulin sensitivity, dyslipidemia and liver fat in obese children.

PubMed

Knøsgaard, L; Kazankov, K; Birkebæk, N H; Holland-Fischer, P; Lange, A; Solvig, J; Hørlyck, A; Kristensen, K; Rittig, S; Vilstrup, H; Grønbæk, H; Handberg, A

2016-09-01

Childhood obesity is a major health problem with serious long-term metabolic consequences. CD36 is important for the development of obesity-related complications among adults. We aimed to investigate circulating sCD36 during weight loss in childhood obesity and its associations with insulin resistance, dyslipidemia, hepatic fat accumulation and low-grade inflammation. The impact of a 10-week weight loss camp for obese children (N=113) on plasma sCD36 and further after a 12-month follow-up (N=68) was investigated. Clinical and biochemical data were collected, and sCD36 was measured by an in-house assay. Liver fat was estimated by ultrasonography and insulin resistance by the homeostasis model assessment (HOMA-IR). Along with marked weight loss, sCD36 was reduced by 21% (P=0.0013) following lifestyle intervention, and individual sCD36 reductions were significantly associated with the corresponding decreases in HOMA-IR, triglycerides and total cholesterol. The largest sCD36 decrease occurred among children who reduced HOMA-IR and liver fat. After 12 months of follow-up, sCD36 was increased (P=0.014) and the metabolic improvements were largely lost. Weight-loss-induced sCD36 reduction, coincident with improved insulin resistance, circulating lipids and hepatic fat accumulation, proposes that sCD36 may be an early marker of long-term health risk associated with obesity-related complications.

The cryo-thermal therapy eradicated melanoma in mice by eliciting CD4+ T-cell-mediated antitumor memory immune response.

PubMed

He, Kun; Liu, Ping; Xu, Lisa X

2017-03-23

Tumor metastasis is a major concern in tumor therapy. In our previous studies, a novel tumor therapeutic modality of the cryo-thermal therapy has been presented, highlighting its effect on the suppression of distal metastasis and leading to long-term survival in 4T1 murine mammary carcinoma model. To demonstrate the therapeutic efficacy in other aggressive tumor models and further investigate the mechanism of long-term survival induced, in this study, spontaneous metastatic murine B16F10 melanoma model was used. The cryo-thermal therapy induced regression of implanted melanoma and prolonged long-term survival while inhibiting lung metastasis. It also promoted the activation of CD4 + CD25 - conventional T cells, while reduced the percentage of CD4 + CD25 + regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in the spleen, lung and blood. Furthermore, the cryo-thermal therapy enhanced the cytolytic function of CD8 + T cells and induced differentiation of CD8 + T cells into memory stem T cell (T SCM ), and differentiation of CD4 + T cells into dominant CD4-CTL, Th1 and Tfh subsets in the spleen for 90 days after the treatment. It was found that good therapeutic effect was mainly dependent on CD4 + T cells providing a durable memory antitumor immune response. At the same time, significant increase of serum IFN-γ was also observed to provide an ideal microenvironment of antitumor immunity. Further study showed that the rejection of re-challenge of B16F10 but not GL261 tumor in the treated mice in 45 or 60 days after the treatment, implied a strong systemic and melanoma-specific memory antitumor immunity induced by the treatment. Thus the cryo-thermal therapy would be considered as a new therapeutic strategy to prevent tumor recurrence and metastasis with potential clinical applications in the near future.

Short-Term Azithromycin Treatment Promotes Cornea Allograft Survival in the Rat

PubMed Central

Hildebrand, Antonia; Eberwein, Philipp; Reinhard, Thomas; Schwartzkopff, Johannes

2013-01-01

Background Any inflammatory response following corneal transplantation may induce rejection and irreversible graft failure. The purpose of this study is to analyze the anti-inflammatory effect of azithromycin (AZM) following experimental keratoplasty in rats. Methods Corneal transplants were performed between Fisher-donor and Lewis-recipient rats. Recipients were postoperatively treated three times daily with AZM, miglyol, ofloxacin or dexamethasone eye drops. As an additional control, AZM was applied following syngeneic keratoplasty. Furthermore, short-term treatments with AZM for seven days perioperatively or with AZM only three days prior to the transplantation were compared to appropriate controls. All transplants were monitored clinically for opacity, edema, and vascularization. Infiltrating CD45+, CD4+, CD8+, CD25+, CD161+ and CD163+ cells were quantified via immunohistochemistry. Results AZM significantly promoted corneal graft survival compared with miglyol or ofloxacin treatment. This effect was comparable to topical dexamethasone. No adverse AZM effect was observed. Histology confirmed a significant reduction of infiltrating leukocytes. The short-term application of AZM for three days prior to transplantation or for seven days perioperatively reduced corneal graft rejection significantly compared with the controls. Conclusions Along with antibiotic properties, topical AZM has a strong anti-inflammatory effect. Following keratoplasty, this effect is comparable to topical dexamethasone without the risk of steroid-induced adverse effects. Short-term treatment with AZM three days prior to the transplantation was sufficient to promote graft survival in the rat keratoplasty model. We therefore suggest further assessing the anti-inflammatory function of topical AZM following keratoplasty in humans. PMID:24349336

Decreased Superoxide Production, Degranulation, Tumor Necrosis Factor Alpha Secretion, and CD11b/CD18 Receptor Expression by Adherent Monocytes from Preterm Infants

PubMed Central

Kaufman, David; Kilpatrick, Laurie; Hudson, R. Guy; Campbell, Donald E.; Kaufman, Ann; Douglas, Steven D.; Harris, Mary C.

1999-01-01

Preterm infants have an increased incidence of infection, which is principally due to deficiencies in neonatal host defense mechanisms. Monocyte adherence is important in localizing cells at sites of infection and is associated with enhanced antimicrobial functions. We isolated cord blood monocytes from preterm and full-term infants to study their adhesion and immune functions, including superoxide (O2−) generation, degranulation, and cytokine secretion and their adhesion receptors. O2− production and degranulation were significantly diminished, by 28 and 37%, respectively, in adherent monocytes from preterm infants compared to full-term infants (P < 0.05); however, these differences were not seen in freshly isolated cells. We also observed a significant decrease of 35% in tumor necrosis factor alpha secretion by lipopolysaccharide-stimulated adherent monocytes from preterm infants compared to full-term infants (P < 0.05); however, this difference was not observed in interleukin-1β or interleukin-6 production by the monocytes. The cell surface expression of the CD11b/CD18 adhesion receptor subunits was significantly decreased (by 60 and 52%, respectively) in monocytes from preterm infants compared to full-term infants (P < 0.01). The cascade of the immune response to infection involves monocyte upregulation and adherence via CD11b/CD18 receptors followed by cell activation and the release of cytokines and bactericidal products. We speculate that monocyte adherence factors may be important in the modulation of immune responses in preterm infants. PMID:10391855

Natural killer cells in highly exposed hepatitis C-seronegative injecting drug users.

PubMed

Mina, M M; Cameron, B; Luciani, F; Vollmer-Conna, U; Lloyd, A R

2016-06-01

Injecting drug use remains the major risk factor for hepatitis C (HCV) transmission. A minority of long-term injecting drug users remain seronegative and aviraemic, despite prolonged exposure to HCV - termed highly exposed seronegative subjects. Natural killer (NK) cells have been implicated in this apparent protection. A longitudinal nested, three group case-control series of subjects was selected from a prospective cohort of seronegative injecting drug users who became incident cases (n = 11), remained seronegative (n = 11) or reported transient high-risk behaviour and remained uninfected (n = 11). The groups were matched by age, sex and initial risk behaviour characteristics. Stored peripheral blood mononuclear cells were assayed in multicolour flow cytometry to enumerate natural killer cell subpopulations and to assess functional activity using Toll-like receptor ligands before measurement of activation, cytokine production and natural cytotoxicity receptor expression. Principal components were derived to describe the detailed phenotypic characteristics of the major NK subpopulations (based on CD56 and CD16 co-expression), before logistic regression analysis to identify associations with exposed, seronegative individuals. The CD56(dim) CD16(+) (P = 0.05, OR 6.92) and CD56(dim) CD16(-) (P = 0.05, OR 6.07) principal components differed between exposed, seronegative individuals and pre-infection samples of the other two groups. These included CD56(dim) CD16(+) and CD56(dim) CD16(-) subsets with CD56(dim) CD16(+) IFN-γ and TNF-α on unstimulated cells, and CD56(dim) CD16(-) CD69(+) , CD107a(+) , IFN-γ and TNF-α following TLR stimulation. The cytotoxic CD56(dim) NK subset thus distinguished highly exposed, seronegative subjects, suggesting NK cytotoxicity may contribute to protection from HCV acquisition. Further investigation of the determinants of this association and prospective assessment of protection against HCV infection are warranted. © 2016 John Wiley & Sons Ltd.

CD-ROM versus Online.

ERIC Educational Resources Information Center

Wiedemer, John David; Boelio, David B.

1995-01-01

Compares compact discs (CD-ROMs) and online services in terms of cost of information delivery; system advantages and disadvantages; future possibilities; and role in the National Information Infrastructure. Analysis reveals that CD-ROMs have the lowest information delivery cost and are endorsed by the marketplace as a cost-effective way to deliver…

Serials Information on CD-ROM: A Reference Perspective.

ERIC Educational Resources Information Center

Karch, Linda S.

1990-01-01

Describes Ulrich's PLUS (a CD-ROM version of Ulrich's serials directories) and EBSCO's CD-ROM version of "The Serials Directory," and compares the two in terms of their use as reference tools. Areas discussed include database content, user aids, system features, search features, and a comparison of search results. Equipment requirements…

Long-Term Effects of Stem Cells on Total-Body Irradiated Mice

NASA Astrophysics Data System (ADS)

Vyalkina, M. V.; Alchinova, I. B.; Yakovenko, E. N.; Medvedeva, Yu S.; Saburina, I. N.; Karganov, M. Yu

2017-01-01

C57Bl/6 mice were exposed to γ-radiation in a sublethal dose of 7.5 Gy. In 3 hours injection 106/mouse of bone marrow multipotent mesenchymal stromal cells stem cells intravenously to experimental group was done. Methods used: body weight measurement, open field behavior, subfraction composition of blood serum (laser correlation spectroscopy, LCS), histological examination of the spleen, liver, and pancreas, count of T and B cells, white blood formula. After 1.5 and 3 months the general trend towards intermediate position of the parameters observed in the experimental between those in intact and irradiated controls attests to partial protective/restorative effects of the injected cells.

Subchronic exposure to sublethal dose of imidacloprid changes electrophysiological properties and expression pattern of nicotinic acetylcholine receptor subtypes in insect neurosecretory cells.

PubMed

Benzidane, Yassine; Goven, Delphine; Abd-Ella, Aly Ahmed; Deshayes, Caroline; Lapied, Bruno; Raymond, Valérie

2017-09-01

Neonicotinoids are the most important class of insecticides used in agriculture over the last decade. They act as selective agonists of insect nicotinic acetylcholine receptors (nAChRs). The emergence of insect resistance to these insecticides is one of the major problems, which limit the use of neonicotinoids. The aim of our study is to better understand physiological changes appearing after subchronic exposure to sublethal doses of insecticide using complementary approaches that include toxicology, electrophysiology, molecular biology and calcium imaging. We used cockroach neurosecretory cells identified as dorsal unpaired median (DUM) neurons, known to express two α-bungarotoxin-insensitive (α-bgt-insensitive) nAChR subtypes, nAChR1 and nAChR2, which differ in their sensitivity to imidacloprid. Although nAChR1 is sensitive to imidacloprid, nAChR2 is insensitive to this insecticide. In this study, we demonstrate that subchronic exposure to sublethal dose of imidacloprid differentially changes physiological and molecular properties of nAChR1 and nAChR2. Our findings reported that this treatment decreased the sensitivity of nAChR1 to imidacloprid, reduced current density flowing through this nAChR subtype but did not affect its subunit composition (α3, α8 and β1). Subchronic exposure to sublethal dose of imidacloprid also affected nAChR2 functions. However, these effects were different from those reported on nAChR1. We observed changes in nAChR2 conformational state, which could be related to modification of the subunit composition (α1, α2 and β1). Finally, the subchronic exposure affecting both nAChR1 and nAChR2 seemed to be linked to the elevation of the steady-state resting intracellular calcium level. In conclusion, under subchronic exposure to sublethal dose of imidacloprid, cockroaches are capable of triggering adaptive mechanisms by reducing the participation of imidacloprid-sensitive nAChR1 and by optimizing functional properties of nAChR2, which is insensitive to this insecticide. Copyright © 2017 Elsevier B.V. All rights reserved.

Gamma rays induce DNA damage and oxidative stress associated with impaired growth and reproduction in the copepod Tigriopus japonicus.

PubMed

Han, Jeonghoon; Won, Eun-Ji; Lee, Bo-Young; Hwang, Un-Ki; Kim, Il-Chan; Yim, Joung Han; Leung, Kenneth Mei Yee; Lee, Yong Sung; Lee, Jae-Seong

2014-07-01

Nuclear radioisotope accidents are potentially ecologically devastating due to their impact on marine organisms. To examine the effects of exposure of a marine organism to radioisotopes, we irradiated the intertidal copepod Tigriopus japonicus with several doses of gamma radiation and analyzed the effects on mortality, fecundity, and molting by assessing antioxidant enzyme activities and gene expression patterns. No mortality was observed at 96h, even in response to exposure to a high dose (800Gy) of radiation, but mortality rate was significantly increased 120h (5 days) after exposure to 600 or 800Gy gamma ray radiation. We observed a dose-dependent reduction in fecundity of ovigerous females; even the group irradiated with 50Gy showed a significant reduction in fecundity, suggesting that gamma rays are likely to have a population level effect. In addition, we observed growth retardation, particularly at the nauplius stage, in individuals after gamma irradiation. In fact, nauplii irradiated with more than 200Gy, though able to molt to copepodite stage 1, did not develop into adults. Upon gamma radiation, T. japonicus showed a dose-dependent increase in reactive oxygen species (ROS) levels, the activities of several antioxidant enzymes, and expression of double-stranded DNA break damage genes (e.g. DNA-PK, Ku70, Ku80). At a low level (sub-lethal dose) of gamma irradiation, we found dose-dependent upregulation of p53, implying cellular damage in T. japonicus in response to sub-lethal doses of gamma irradiation, suggesting that T. japonicus is not susceptible to sub-lethal doses of gamma irradiation. Additionally, antioxidant genes, phase II enzyme (e.g. GSTs), and cellular chaperone genes (e.g. Hsps) that are involved in cellular defense mechanisms also showed the same expression patterns for sublethal doses of gamma irradiation (50-200Gy). These findings indicate that sublethal doses of gamma radiation can induce oxidative stress-mediated DNA damage and increase the expression of antioxidant enzymes and proteins with chaperone-related functions, thereby significantly affecting life history parameters such as fecundity and molting in the copepod T. japonicus. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of sub-lethal neurite outgrowth inhibitory concentrations of chlorpyrifos oxon on cytoskeletal proteins and acetylcholinesterase in differentiating N2a cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flaskos, J., E-mail: flaskos@vet.auth.gr; Nikolaidis, E.; Harris, W.

2011-11-15

Previous work in our laboratory has shown that sub-lethal concentrations (1-10 {mu}M) of chlorpyrifos (CPF), diazinon (DZ) and diazinon oxon (DZO) inhibit the outgrowth of axon-like neurites in differentiating mouse N2a neuroblastoma cells concomitant with altered levels and/or phosphorylation state of axonal cytoskeleton and growth-associated proteins. The aim of the present work was to determine whether chlorpyrifos oxon (CPO) was capable of inhibiting N2a cell differentiation in a similar manner. Using experimental conditions similar to our previous work, sub-lethal concentrations (1-10 {mu}M) of CPO were found to inhibit N2a cell differentiation. However, unlike previous studies with DZ and DZO, theremore » was a high level of sustained inhibition of acetylcholinesterase (AChE) in CPO treated cells. Impairment of neurite outgrowth was also associated with reduced levels of growth associated protein-43 and neurofilament heavy chain (NFH), and the distribution of NFH in cells stained by indirect immunofluorescence was disrupted. However, in contrast to previous findings for DZO, the absolute level of phosphorylated NFH was unaffected by CPO exposure. Taken together, the findings suggest that sub-lethal concentrations of CPO inhibit axon outgrowth in differentiating N2a cells and that this effect involves reduced levels of two proteins that play key roles in axon outgrowth and maintenance. Although the inhibition of neurite outgrowth is unlikely to involve AChE inhibition directly, further work will help to determine whether the persistent inhibition of AChE by CPO can account for the different effects induced by CPO and DZO on the levels of total and phosphorylated NFH. -- Highlights: Black-Right-Pointing-Pointer Sub-lethal levels of chlorpyrifos oxon inhibit neurite outgrowth in N2a cells Black-Right-Pointing-Pointer Acetylcholinesterase exhibits sustained inhibition throughout exposure Black-Right-Pointing-Pointer The levels of neurofilament heavy chain and GAP-43 protein are reduced Black-Right-Pointing-Pointer Neurofilament heavy chain forms aggregates in cell bodies Black-Right-Pointing-Pointer Thus at least two axon-associated cytoskeletal proteins are disrupted by this agent.« less

Frequent and seasonally variable sublethal anthrax infections are accompanied by short-lived immunity in an endemic system

PubMed Central

Cizauskas, Carrie A.; Bellan, Steven E.; Turner, Wendy C.; Vance, Russell E.; Getz, Wayne M.

2014-01-01

Summary Few studies have examined host-pathogen interactions in wildlife from an immunological perspective, particularly in the context of seasonal and longitudinal dynamics. In addition, though most ecological immunology studies employ serological antibody assays, endpoint titer determination is usually based on subjective criteria and needs to be made more objective. Despite the fact that anthrax is an ancient and emerging zoonotic infectious disease found worldwide, its natural ecology is not well understood. In particular, little is known about the adaptive immune responses of wild herbivore hosts against Bacillus anthracis. Working in the natural anthrax system of Etosha National Park, Namibia, we collected 154 serum samples from plains zebra (Equus quagga), 21 from springbok (Antidorcas marsupialis), and 45 from African elephants (Loxodonta africana) over 2-3 years, resampling individuals when possible for seasonal and longitudinal comparisons. We used enzyme-linked immunosorbent assays to measure anti-anthrax antibody titers and developed three increasingly conservative models to determine endpoint titers with more rigorous, objective mensuration. Between 52-87% of zebra, 0-15% of springbok, and 3-52% of elephants had measurable anti-anthrax antibody titers, depending on the model used. While the ability of elephants and springbok to mount anti-anthrax adaptive immune responses is still equivocal, our results indicate that zebra in ENP often survive sublethal anthrax infections, encounter most B. anthracis in the wet season, and can partially booster their immunity to B. anthracis. Thus, rather than being solely a lethal disease, anthrax often occurs as a sublethal infection in some susceptible hosts. Though we found that adaptive immunity to anthrax wanes rapidly, subsequent and frequent sublethal B. anthracis infections cause maturation of anti-anthrax immunity. By triggering host immune responses, these common sublethal infections may act as immunomodulators and affect population dynamics through indirect immunological and co-infection effects. In addition, with our three endpoint titer models, we introduce more mensuration rigor into serological antibody assays, even under the often-restrictive conditions that come with adapting laboratory immunology methods to wild systems. With these methods we identified significantly more zebras responding immunologically to anthrax than have previous studies using less comprehensive titer analyses. PMID:24499424

Long-term field phytoextraction of zinc/cadmium contaminated soil by Sedum plumbizincicola under different agronomic strategies.

PubMed

Deng, Lin; Li, Zhu; Wang, Jie; Liu, Hongyan; Li, Na; Wu, Longhua; Hu, Pengjie; Luo, Yongming; Christie, Peter

2016-01-01

In two long-term field experiments the zinc (Zn)/cadmium (Cd) hyperaccumulator Sedum plumbizincicola (S. plumbizincicola) was examined to optimize the phytoextraction of metal contaminated soil by two agronomic strategies of intercropping with maize (Zea mays) and plant densities. Soil total Zn and Cd concentrations decreased markedly after long-term phytoextraction. But shoot biomass and Cd and Zn concentrations showed no significant difference with increasing remediation time. In the intercropping experiment the phytoremediation efficiency in the treatment "S. plumbizincicola intercropped with maize" was higher than in S. plumbizincicola monocropping, and Cd concentrations of corn were below the maximum national limit. In the plant density experiment the phytoremediation efficiency increased with increasing plant density and 440,000 plants ha(-1) gave the maximum rate. These results indicated that S. plumbizincicola at an appropriate planting density and intercropped with maize can achieve high remediation efficiency to contaminated soil without affecting the cereal crop productivity. This cropping system combines adequate agricultural production with soil heavy metal phytoextraction.

Impacts of Sublethal Mercury Exposure on Birds: A Detailed Review.

PubMed

Whitney, Margaret C; Cristol, Daniel A

Mercury is a ubiquitous environmental contaminant known to accumulate in, and negatively affect, fish-eating and oceanic bird species, and recently demonstrated to impact some terrestrial songbirds to a comparable extent. It can bioaccumulate to concentrations of >1 μg/g in tissues of prey organisms such as fish and insects. At high enough concentrations, exposure to mercury is lethal to birds. However, environmental exposures are usually far below the lethal concentrations established by dosing studies.The objective of this review is to better understand the effects of sublethal exposure to mercury in birds. We restricted our survey of the literature to studies with at least some exposures >5 μg/g. The majority of sublethal effects were subtle and some studies of similar endpoints reached different conclusions. Strong support exists in the literature for the conclusion that mercury exposure reduces reproductive output, compromises immune function, and causes avoidance of high-energy behaviors. For some endpoints, notably certain measures of reproductive success, endocrine and neurological function, and body condition, there is weak or contradictory evidence of adverse effects and further study is required. There was no evidence that environmentally relevant mercury exposure affects longevity, but several of the sublethal effects identified likely do result in fitness reductions that could adversely impact populations. Overall, 72% of field studies and 91% of laboratory studies found evidence of deleterious effects of mercury on some endpoint, and thus we can conclude that mercury is harmful to birds, and the many effects on reproduction indicate that bird population declines may already be resulting from environmental mercury pollution.

Chronic sublethal effects of San Francisco Bay sediments on nereis (neanthes) arenaceodentata; effect of food ration on sediment toxicity. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moore, D.W.; Dillon, T.M.

1993-09-01

This report is designed to address concerns regarding the effect of food ration on toxicity during chronic sublethal sediment bioassays. To this end, a contaminated San Francisco Bay sediment and a clean control sediment were evaluated in a chronic sublethal test under a series of different food rations, with the marine polychaete worm Nereis (Neanthes) arenaceodentata. Animals were exposed from early juvenile stage through the onset of gametogenesis. Treatments were 2.OX, 1.OX, 0.5X, and 0.25X where X is the recommended food ration for laboratory cultures. Test end points were survival, growth, and reproduction. The contaminated sediment was a composite ofmore » several cores taken to project depth (38 ft (11.6 m) below mean low water mark) from an area in Oakland Inner Harbor known to be contaminated with polycyclic aromatic hydrocarbons and metals. Comparisons were made with a clean control sediment. The control sediment is used in the laboratory cultures of N. arenaceodentata and was collected from Sequim, WA. Mean percent survival of Neanthes was high (>90 percent) in both the contaminated and control sediment across all food ration treatments. Individual wet weights were significantly reduced with decreasing food ration in both contaminated and control sediments. Significant differences in wet weight between sediment types were observed at the 1.OX, 0.5X, and 0.25X rations. Reproduction (fecundity and emergent juvenile (EJ) production) was also Chronic sublethal, Neanthes, Dredged material, San Francisco Bay, Food ration, Sediment.« less

Suppression of HIV Replication by Lymphoid Tissue CD8+ Cells Correlates with the Clinical State of HIV-Infected Individuals

NASA Astrophysics Data System (ADS)

Blackbourn, David J.; Mackewicz, Carl E.; Barker, Edward; Hunt, Thomas K.; Herndier, Brian; Haase, Ashley T.; Levy, Jay A.

1996-11-01

Lymphoid tissues from asymptomatic HIV-infected individuals, as compared with symptomatic HIV-infected subjects, show limited histopathological changes and lower levels of HIV expression. In this report we correlate the control of HIV replication in lymph nodes to the non-cytolytic anti-HIV activity of lymphoid tissue CD8+ cells. Five subjects at different stages of HIV-related disease were studied and the ability of their CD8+ cells, isolated from both lymphoid tissue and peripheral blood, to inhibit HIV replication was compared. CD8+ cells from lymphoid tissue and peripheral blood of two HIV-infected long-term survivors suppressed HIV replication at a low CD8+:CD4+ cell ratio of 0.1. The CD8+ cells from the lymphoid tissue of a third asymptomatic subject suppressed HIV replication at a CD8+:CD4+ cell ratio of 0.25; the subject's peripheral blood CD8+ cells showed this antiviral response at a lower ratio of 0.05. The lymphoid tissue CD8+ cells from two AIDS patients were not able to suppress HIV replication, and the peripheral blood CD8+ cells of only one of them suppressed HIV replication. The plasma viremia, cellular HIV load as well as the extent of pathology and virus expression in the lymphoid tissue of the two long-term survivors, were reduced compared with these parameters in the three other subjects. The data suggest that the extent of anti-HIV activity by CD8+ cells from lymphoid tissue relative to peripheral blood correlates best with the clinical state measured by lymphoid tissue pathology and HIV burden in lymphoid tissues and blood. The results and further emphasis to the importance of this cellular immune response in controlling HIV pathogenesis.

A Regional Outbreak of Clostridium difficile PCR-Ribotype 027 Infections in Southeastern France from a Single Long-Term Care Facility.

PubMed

Cassir, Nadim; Delarozière, Jean-Christophe; Dubourg, Gregory; Delord, Marion; Lagier, Jean-Christophe; Brouqui, Phillipe; Fenollar, Florence; Raoult, Didier; Fournier, Pierre Edouard

2016-11-01

OBJECTIVE To describe and analyze a large outbreak of Clostridium difficile 027 (CD-027) infections. METHODS Confirmed CD-027 cases were defined as CD infection plus real-time polymerase chain reaction assay (PCR) positive for CD-027. Clinical and microbiological data on patients with CD-027 infection were collected from January 2013 to December 2015 in the Provence-Alpes-Côte-d'Azur region (southeastern France). RESULTS In total, 19 healthcare facilities reported 144 CD-027 infections (112 confirmed and 32 probable CD-027 infections) during a 22-month period outbreak. Although the incidence rate per 10,000 bed days was lower in long-term care facilities (LTCFs) than in acute care facilities (0.05 vs 0.14; P<.001), cases occurred mainly in LTCFs, one of which was the probable source of this outbreak. After centralization of CD testing, the rate of confirmed CD-027 cases from LTCFs or residential-care homes increased significantly (69% vs 92%; P<.001). Regarding confirmed CD-027 patients, the sex ratio and the median age were 0.53 and 84.2 years, respectively. The 30-day crude mortality rate was 31%. Most patients (96%) had received antibiotics within 3 months prior to the CD colitis diagnosis. During the study period, the rate of patients with CD-027 (compared with all patients tested in the point-of-care laboratories) decreased significantly (P=.03). CONCLUSIONS A large CD-027 outbreak occurred in southeastern France as a consequence of an initial cluster of cases in a single LTCF. Successful interventions included rapid isolation and testing of residents with potentially infectious diarrhea and cohorting of case patients in a specialized infectious diseases ward to optimize management. Infect Control Hosp Epidemiol 2016;1-5.

Long-term mortality in HIV-positive individuals virally suppressed for >3 years with incomplete CD4 recovery.

PubMed

Engsig, Frederik N; Zangerle, Robert; Katsarou, Olga; Dabis, Francois; Reiss, Peter; Gill, John; Porter, Kholoud; Sabin, Caroline; Riordan, Andrew; Fätkenheuer, Gerd; Gutiérrez, Félix; Raffi, Francois; Kirk, Ole; Mary-Krause, Murielle; Stephan, Christoph; de Olalla, Patricia Garcia; Guest, Jodie; Samji, Hasina; Castagna, Antonella; d'Arminio Monforte, Antonella; Skaletz-Rorowski, Adriane; Ramos, Jose; Lapadula, Giuseppe; Mussini, Cristina; Force, Lluís; Meyer, Laurence; Lampe, Fiona; Boufassa, Faroudy; Bucher, Heiner C; De Wit, Stéphane; Burkholder, Greer A; Teira, Ramon; Justice, Amy C; Sterling, Tim R; M Crane, Heidi; Gerstoft, Jan; Grarup, Jesper; May, Margaret; Chêne, Geneviève; Ingle, Suzanne M; Sterne, Jonathan; Obel, Niels

2014-05-01

Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/µL after 3 years of sustained viral suppression and (2) the association of the achieved CD4 count with subsequent mortality. We included treated HIV-infected adults from 2 large international HIV cohorts, who had viral suppression (≤500 HIV type 1 RNA copies/mL) for >3 years with CD4 count ≤200 cells/µL at start of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery (≤200 cells/µL) and Cox regression to identify associations with mortality. Of 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/µL after 3 years of suppression. Increasing age, lower initial CD4 count, male heterosexual and injection drug use transmission, cART initiation after 1998, and longer time from initiation of cART to start of the virally suppressed period were risk factors for not achieving a CD4 count >200 cells/µL. Individuals with CD4 ≤200 cells/µL after 3 years of viral suppression had substantially increased mortality (adjusted hazard ratio, 2.60; 95% confidence interval, 1.86-3.61) compared with those who achieved CD4 count >200 cells/µL. The increased mortality was seen across different patient groups and for all causes of death. Virally suppressed HIV-positive individuals on cART who do not achieve a CD4 count >200 cells/µL have substantially increased long-term mortality.

Spontaneous Self-Assembly of Polymeric Nanoparticles in Aqueous Media: New Insights From Microfluidics, In Situ Size Measurements, and Individual Particle Tracking.

PubMed

Li, Xue; Salzano, Giuseppina; Zhang, Jiwen; Gref, Ruxandra

2017-01-01

Supramolecular cyclodextrin-based nanoparticles (CD-NPs) mediated by host-guest interactions have gained increased popularity because of their "green" and simple preparation procedure, as well as their versatility in terms of inclusion of active molecules. Herein, we showed that original CD-NPs of around 100 nm are spontaneously formed in water, by mixing 2 aqueous solutions of (1) a CD polymer and (2) dextran grafted with benzophenone moieties. For the first time, CD-NPs were instantaneously produced in a microfluidic interaction chamber by mixing 2 aqueous solutions of neutral polymers, in the absence of organic solvents. Whatever the mixing conditions, CD-NPs with narrow size distributions were immediately formed upon contact of the 2 polymeric solutions. In situ size measurements showed that the CD-NPs were spontaneously formed. Nanoparticle tracking analysis was used to individually follow the CD-NPs in their Brownian motions, to gain insights on their size distribution, concentration, and stability on extreme dilution. Nanoparticle tracking analysis allowed to establish that despite their non-covalent nature, and the CD-NPs were remarkably stable in terms of concentration and size distribution, even on extreme dilution (concentrations as low as 100 ng/mL). Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Contribution diversity and incremental learning promote cooperation in public goods games

NASA Astrophysics Data System (ADS)

Liu, Penghui; Liu, Jing

2017-11-01

Understanding the evolution of cooperation in nature has long been a challenge and how to promote cooperation in public goods games (PGG) has attracted lots of attention recently. Social diversity has been found helpful to explain the emergence of cooperation in the absence of reputation and punishment. However, further refinement on how individuals reallocate their contribution to each PGG remains an open question. Moreover, individuals in existing works mostly teach or learn from neighbors according to their payoff in the last generation only. However, individuals in reality are preferred to learn from others with a long-term good performance. Therefore, in this paper, a new contribution diversity (CD) is designed and incremental learning (IL) is introduced. We investigate how these two may influence the evolution of cooperation in PGG. Based on the simulation results, we found that both the CD and IL can promote the cooperation in PGGs. Moreover, when cooperators are shaken in their strategy, CD may fail in reallocating contribution of individuals properly. However, IL is found effective to stabilize faith of cooperators and cooperators under IL reflect a long-term advantage over defectors in terms of benefits. Therefore, we further find IL and CD can mutually benefit each other in promoting cooperation, as CD can reasonably adjust the investment of cooperators while IL can provide more information to CD.

Cyclosporine therapy in inflammatory bowel disease: short-term and long-term results.

PubMed

Gurudu, S R; Griffel, L H; Gialanella, R J; Das, K M

1999-09-01

Intravenous cyclosporine therapy followed by oral cyclosporine therapy reduce the need for urgent surgery in steroid-refractory inflammatory bowel disease (IBD). Our objective is to report short- and long-term results of cyclosporine therapy in IBD patients. Thirteen patients with steroid-refractory IBD, seven patients with ulcerative colitis (UC), and six patients with Crohn's disease (CD) were treated with intravenous cyclosporine (4 mg/kg/day) for a mean period of 11.4+/-2.8 days (range, 4-15 days). Subsequently the patients were started on oral cyclosporine (8 mg/kg/day) and followed for a mean of 10.3+/-10 months (range, 1-30 months). Twelve patients responded to intravenous cyclosporine therapy. One patient with UC developed sepsis on the fourth day of intravenous cyclosporine therapy and needed urgent colectomy. Nine of 12 initial responders (6 patients with UC and 3 patients with CD) relapsed during follow-up despite oral cyclosporine and underwent elective surgery. One patient with CD relapsed 3 months after discontinuation of oral cyclosporine. Only two patients with CD are in long-term remission. There were no long-term side effects in any of the 13 treated patients. In conclusion, intravenous cyclosporine was effective in inducing remission or significant improvement in 12 of 13 patients with steroid-refractory IBD. However, with subsequent oral cyclosporine the remission could be maintained only for a short while. Each of the six patients with UC needed colectomy and three of the five patients with CD had intestinal resection within 12 months despite oral cyclosporine therapy.

Progesterone and HMOX-1 promote fetal growth by CD8+ T cell modulation

PubMed Central

Solano, María Emilia; Kowal, Mirka Katharina; O’Rourke, Greta Eugenia; Horst, Andrea Kristina; Modest, Kathrin; Plösch, Torsten; Barikbin, Roja; Remus, Chressen Catharina; Berger, Robert G.; Jago, Caitlin; Ho, Hoang; Sass, Gabriele; Parker, Victoria J.; Lydon, John P.; DeMayo, Francesco J.; Hecher, Kurt; Karimi, Khalil; Arck, Petra Clara

2015-01-01

Intrauterine growth restriction (IUGR) affects up to 10% of pregnancies in Western societies. IUGR is a strong predictor of reduced short-term neonatal survival and impairs long-term health in children. Placental insufficiency is often associated with IUGR; however, the molecular mechanisms involved in the pathogenesis of placental insufficiency and IUGR are largely unknown. Here, we developed a mouse model of fetal-growth restriction and placental insufficiency that is induced by a midgestational stress challenge. Compared with control animals, pregnant dams subjected to gestational stress exhibited reduced progesterone levels and placental heme oxygenase 1 (Hmox1) expression and increased methylation at distinct regions of the placental Hmox1 promoter. These stress-triggered changes were accompanied by an altered CD8+ T cell response, as evidenced by a reduction of tolerogenic CD8+CD122+ T cells and an increase of cytotoxic CD8+ T cells. Using progesterone receptor– or Hmox1-deficient mice, we identified progesterone as an upstream modulator of placental Hmox1 expression. Supplementation of progesterone or depletion of CD8+ T cells revealed that progesterone suppresses CD8+ T cell cytotoxicity, whereas the generation of CD8+CD122+ T cells is supported by Hmox1 and ameliorates fetal-growth restriction in Hmox1 deficiency. These observations in mice could promote the identification of pregnancies at risk for IUGR and the generation of clinical interventional strategies. PMID:25774501

Toxicity and motor changes in Africanized honey bees (Apis mellifera L.) exposed to fipronil and imidacloprid.

PubMed

Bovi, Thaís S; Zaluski, Rodrigo; Orsi, Ricardo O

2018-01-01

This study evaluated the in vitro toxicity and motor activity changes in African-derived adult honey bees (Apis mellifera L.) exposed to lethal or sublethal doses of the insecticides fipronil and imidacloprid. Mortality of bees was assessed to determine the ingestion and contact lethal dose for 24 h using probit analysis. Motor activities in bees exposed to lethal (LD50) and sublethal doses (1/500th of the lethal dose) of both insecticides were evaluated in a behavioral observation box at 1 and 4 h. Ingestion and contact lethal doses of fipronil were 0.2316 ? 0.0626 and 0.0080 ? 0.0021 μg/bee, respectively. Ingestion and contact lethal doses of imidacloprid were 0.1079 ? 0.0375 and 0.0308 ? 0.0218 μg/bee, respectively. Motor function of bees exposed to lethal doses of fipronil and imidacloprid was impaired; exposure to sublethal doses of fipronil but not imidacloprid impaired motor function. The insecticides evaluated in this study were highly toxic to African-derived A. mellifera and caused impaired motor function in these pollinators.

Size-selective toxicity effects of the antimicrobial tylosin on estuarine phytoplankton communities.

PubMed

Kline, Allison; Pinckney, James L

2016-09-01

The purpose of this study was to determine the lethal and sublethal effects of the antimicrobial tylosin on natural estuarine phytoplankton communities. Bioassays were used in experimental treatments with final concentrations of 5 to 1000 μg tylosin l(-1). Maximum percent inhibition ranged from 57 to 85% at concentrations of 200-400 μg tylosin l(-1). Half maximum inhibition concentrations of tylosin were ca. 5x lower for small phytoplankton (<20 μm) relative to larger phytoplankton (>20 μm) and suggests that small phytoplankton are more sensitive to tylosin exposure. Sublethal effects occurred at concentrations as low as 5 μg tylosin l(-1). Environmental concentrations of tylosin (e.g., 0.2-3 μg l(-1)) may have a significant sublethal effect that alters the size structure and composition of phytoplankton communities. The results of this study highlight the potential importance of cell size on toxicity responses of estuarine phytoplankton. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sublethal effects of phenanthrene, nicotine, and pinane on Daphnia pulex

USGS Publications Warehouse

Savino, Jacqueline F.; Tanabe, Lila L.

1989-01-01

Chronic studies of Daphnia Pulex exposed to different concentrations of phenanthrene, nicotine, and pinane produced consistent sublethal effects among replicates and concentrations. The LOEC's for growth and fecundity with each chemical tested were 3 to 30% of the 48-hr EC50's. Growth decreased as concentration increased for each chemical tested, and fecundity approached zero at 2 to 5 times the LOEC for each chemical. In this study chemicals representing PAHs, heterocyclic nitrogen compounds, and cyclic alkanes, produced detectable sublethal effects in daphnids at less than 0.1 ppm in water. These chronic studies, in conjuction with the more extensive acute toxicity testing (Passino and Smith 1987; Perry and Smith 1988; Smith et al. 1988), provided a relatively quick but thorough toxicological assessment of a large array of chemicals and demonstrated the relative importance of different classes of compounds in changing growth and survival trends in given populations of native organisms. Classic toxicity tests continue to provide a reliable backdrop of results with which the effects of new chemicals or mixtures can be compared.

Sublethal effects of acaricides and Nosema ceranae infection on immune related gene expression in honeybees.

PubMed

Garrido, Paula Melisa; Porrini, Martín Pablo; Antúnez, Karina; Branchiccela, Belén; Martínez-Noël, Giselle María Astrid; Zunino, Pablo; Salerno, Graciela; Eguaras, Martín Javier; Ieno, Elena

2016-04-26

Nosema ceranae is an obligate intracellular parasite and the etiologic agent of Nosemosis that affects honeybees. Beside the stress caused by this pathogen, honeybee colonies are exposed to pesticides under beekeeper intervention, such as acaricides to control Varroa mites. These compounds can accumulate at high concentrations in apicultural matrices. In this work, the effects of parasitosis/acaricide on genes involved in honeybee immunity and survival were evaluated. Nurse bees were infected with N. ceranae and/or were chronically treated with sublethal doses of coumaphos or tau-fluvalinate, the two most abundant pesticides recorded in productive hives. Our results demonstrate the following: (1) honeybee survival was not affected by any of the treatments; (2) parasite development was not altered by acaricide treatments; (3) coumaphos exposure decreased lysozyme expression; (4) N. ceranae reduced levels of vitellogenin transcripts independently of the presence of acaricides. However, combined effects among stressors on imagoes were not recorded. Sublethal doses of acaricides and their interaction with other ubiquitous parasites in colonies, extending the experimental time, are of particular interest in further research work.

Lethal and sublethal effects of four essential oils on the egg parasitoids Trissolcus basalis.

PubMed

Werdin González, Jorge Omar; Laumann, Raúl Alberto; da Silveira, Samantha; Moraes, Maria Carolina Blassioli; Borges, Miguel; Ferrero, Adriana Alicia

2013-07-01

The essential oils from leaves of Schinus molle var. areira, Aloysia citriodora, Origanum vulgare and Thymus vulgaris have showed potential as phytoinsecticides against the green stink bug, Nezara viridula. In this work were evaluated their toxicological and behavioral effects on the parasitoid Trissolcus basalis, a biological control agent of this pest insect. Essential oils were obtained via hydrodestillation from fresh leaves. Insecticide activity in T. basalis females was evaluated in direct contact and fumigation bioassays. Behavioral effects were evaluated in olfactometer bioassays. To evaluate the residual toxicity, females of the parasitoids were exposed to oil residues; in these insects, the sublethal effects were evaluated (potential parasitism and survivorship of immature stages). The essential oils from O. vulgare and T. vulgaris proved to be highly selective when used as fumigant and did not change parasitoid behavior. After one week, the residues of these oils were harmless and did not show sublethal effects against T. basalis. According with these results, essential oils have potential applications for the integrated management of N. viridula. Published by Elsevier Ltd.

Effect of single and binary combinations of plant-derived molluscicides on reproduction and survival of the snail Achatina fulica.

PubMed

Rao, I G; Singh, D K

2000-11-01

The effects of sublethal treatments (20% and 60% of LC(50)/24 h) with plant-derived molluscicides on the reproduction of the giant African snail Achatina fulica were studied. Azadirachta indica oil, Cedrus deodara oil, Allium sativum bulb powder, and Nerium indicum bark powder singly and binary combinations on reproduction and survival of A. fulica were investigated. Repeated treatment occurred on day 0, day 15, and day 30. These plant-derived molluscicides significantly reduced fecundity, egg viability, and survival of A. fulica within 15 days. Discontinuation of the treatments after day 30 did not lead to a recovery trend in the next 30 days. Day 0 sublethal treatment of all the molluscicides caused a maximum reduction in protein, amino acid, DNA, RNA, and phospholipid levels and simultaneous increase in lipid peroxidation in the ovotestis of treated A. fulica. It is believed that sublethal exposure of these molluscicides on snail reproduction is a complex process, involving more than one factor in reducing the reproductive capacity of A. fulica.

Sublethal Effects of Essential Oils From Eucalyptus staigeriana (Myrtales: Myrtaceae), Ocimum gratissimum (Lamiales: Laminaceae), and Foeniculum vulgare (Apiales: Apiaceae) on the Biology of Spodoptera frugiperda (Lepidoptera: Noctuidae).

PubMed

Cruz, G S; Wanderley-Teixeira, V; Oliveira, J V; Lopes, F S C; Barbosa, D R S; Breda, M O; Dutra, K A; Guedes, C A; Navarro, D M A F; Teixeira, A A C

2016-04-01

Spodoptera frugiperda (Smith 1797) (Lepidoptera: Noctuidae) is a major pest of maize, Zea mays L. Its control is often achieved through repeated applications per season of insecticides, which may lead to adverse effects on the ecosystem. Thus, the study of alternative methods with less environmental impact has expanded to include the use of essential oils. These oils are products of the secondary metabolism in plants, and their insecticidal activity has been widely demonstrated in populations of many pest insects. This study evaluated the insecticidal activities of essential oils from Eucalyptus staigeriana, Ocimum gratissimum, and Foeniculum vulgare on Spodoptera frugiperda. Gas chromatography–mass spectrometry profiles and contact toxicity of these oils as well as their sublethal effects on larvae and reproductive parameters in adults were evaluated. All three oils had sublethal effects on S. frugiperda; however, the oil of O. gratissimum showed the best results at all doses tested. These essential oils may have promise for control of S. frugiperda.

Effects of effluent from electoplating industry on the immune response in the freshwater fish, Cyprinus carpio.

PubMed

Borgia, V J Florence; Thatheyus, A J; Murugesan, A G; Alexander, S Catherine P; Geetha, I

2018-08-01

The present study was designed to assess the effect of sublethal concentrations of electoplating industry effluent (EIE) on the non-specific and specific immune responses in the freshwater fish, Cyprinus carpio. Sublethal concentrations of electroplating industry effluent such as 0.004, 0.007, 0.010 and 0.013% were chosen based on the LC 50 values. Experimental fish were exposed to these sublethal concentrations of EIE for 28 days. After 7, 14, 21 and 28 days of treatment, non-specific immune response by serum lysozyme activity, myeloperoxidase activity and antiprotease activity and specific immune response by antibody response to Aeromonas hydrophila using bacterial agglutination assay and ELISA were assessed. The results showed that chronic exposure of fish to 0.004, 0.007, 0.010 and 0.013% EIE, dose-dependently decreased the non-specific and specific immune responses on all the days tested compared to control fish whereas statistically significant suppressive effects were observed in fish exposed to 0.013% of EIE on all activities tested. Copyright © 2018 Elsevier Ltd. All rights reserved.

Enhancement of committed hematopoietic stem cell colony formation by nandrolone decanoate after sublethal whole body irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gallicchio, V.S.; Chen, M.G.; Watts, T.D.

1984-11-01

The ability of an anabolic steroid, nandrolone decanoate, to increase committed topoietic stem cell (CFU-gm, CFU-e, and BFU-e) colony formation after sublethal irradiation was evaluated. Immediately after receiving whole body irradiation and on the next two days, each mouse was injected intraperitoneally with nandrolone decanoate (1.25 mg) in propylene glycol. Irradiated control mice received only propylene glycol. Compared to controls, drug-treated mice showed marked peripheral blood leukocytosis and more stable packed red cell volume. Drug-treated mice also demonstrated increased erythropoiesis, as CFU-e/BFU-e concentrations from both marrow (9% to 581%) and spleen (15% to 797%) were elevated. Granulopoiesis was increased similarly,more » as CFU-gm concentrations from marrow (38% to 685%) and spleen (9% to 373%) were elevated. These results demonstrate that nandrolone decanoate enhances hematopoietic stem cell recovery after sublethal whole body irradiation. This suggests that following hematopoietic suppression, nandrolone decanoate may stimulate the recovery of hematopoiesis at the stem cell level and in peripheral blood.« less

Modelling cadmium contamination in paddy soils under long-term remediation measures: Model development and stochastic simulations.

PubMed

Peng, Chi; Wang, Meie; Chen, Weiping

2016-09-01

A pollutant accumulation model (PAM) based on the mass balance theory was developed to simulate long-term changes of heavy metal concentrations in soil. When combined with Monte Carlo simulation, the model can predict the probability distributions of heavy metals in a soil-water-plant system with fluctuating environmental parameters and inputs from multiple pathways. The model was used for evaluating different remediation measures to deal with Cd contamination of paddy soils in Youxian county (Hunan province), China, under five scenarios, namely the default scenario (A), not returning paddy straw to the soil (B), reducing the deposition of Cd (C), liming (D), and integrating several remediation measures (E). The model predicted that the Cd contents of soil can lowered significantly by (B) and those of the plants by (D). However, in the long run, (D) will increase soil Cd. The concentrations of Cd in both soils and rice grains can be effectively reduced by (E), although it will take decades of effort. The history of Cd pollution and the major causes of Cd accumulation in soil were studied by means of sensitivity analysis and retrospective simulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Distinctive phytotoxic effects of Cd and Ni on membrane functionality.

PubMed

Sanz, Amparo; Llamas, Andreu; Ullrich, Cornelia I

2009-10-01

Metal ions essential for plant growth, such as Fe, Mn, Ni, Cu or Zn, are taken up by plants from the soil solution through metal transporters at the plasma membrane, mainly of the ZIP and Nramp families. These transport systems, however, can also give entry to other metals (Al, Cd, Hg, Pb). Non-nutritive elements, as well as the essential nutrients at higher than metabolic concentrations, can cause phytotoxicity. We have studied previously the effects of an essential (Ni) and a non essential (Cd) heavy metal on root cell plasma membranes, the first selective barrier encountered when entering the plant, using rice as model plant. Distinctive effects of Cd and Ni on membrane function (i.e., Em and membrane permeability) were observed in the short term. We have now confirmed the pattern of Em changes caused by Cd and Ni using barley roots and have also followed the effects of both metals in longer term in rice. Our data indicate that the distinct effects caused by Cd and Ni are due to differences in cellular responses, triggered when entering the cytoplasm (i.e., an efficient detoxifying mechanism for Cd), more than to different direct effects on membranes.

Long-term botulinum toxin treatment increases employment rate in patients with cervical dystonia.

PubMed

Skogseid, Inger Marie; Røislien, Jo; Claussen, Bjørgulf; Kerty, Emilia

2005-12-01

We examined the impact of cervical dystonia (CD) and long-term botulinum toxin (BTX) treatment on employment status. Data on employment status at onset of CD, at initiation of BTX treatment, and at evaluation of long-term treatment were obtained from 62 CD patients aged 31-66 years (median, 53 years; 61% females) who had been treated for a median of 5 years (range, 1.5-10 years). The employment rate fell from 84% at the onset of CD to 47% before initiation of BTX treatment. With long-term BTX treatment, 72% of those who worked at the initiation of treatment stayed employed, and 67% of those on sick leave returned to work. A younger age and a higher level of education increased the probability of being employed and avoiding disability benefits. Among those who were younger than 55 years at evaluation of BTX treatment (n = 40), the employment rate increased from 47% to 65% with treatment, and among the male patients, it reached the level of the general population (86%). About half of the 34% who received disability benefits did so already before the BTX treatment was initiated.

Characterization of Effector and Memory T Cell Subsets in the Immune Response to Bovine Tuberculosis in Cattle

PubMed Central

Maggioli, Mayara F.; Palmer, Mitchell V.; Thacker, Tyler C.; Vordermeier, H. Martin; Waters, W. Ray

2015-01-01

Cultured IFN-γ ELISPOT assays are primarily a measure of central memory T cell (Tcm) responses with humans; however, this important subset of lymphocytes is poorly characterized in cattle. Vaccine-elicited cultured IFN-γ ELISPOT responses correlate with protection against bovine tuberculosis in cattle. However, whether this assay measures cattle Tcm responses or not is uncertain. The objective of the present study was to characterize the relative contribution of Tcm (CCR7+, CD62Lhi, CD45RO+), T effector memory (Tem, defined as: CCR7-, CD62Llow/int, CD45RO+), and T effector cells (CCR7-, CD62L-/low, CD45RO-), in the immune response to Mycobacterium bovis. Peripheral blood mononuclear cells (PBMC) from infected cattle were stimulated with a cocktail of M. bovis purified protein derivative, rTb10.4 and rAg85A for 13 days with periodic addition of fresh media and rIL-2. On day 13, cultured PBMC were re-stimulated with medium alone, rESAT-6:CFP10 or PPDb with fresh autologous adherent cells for antigen presentation. Cultured cells (13 days) or fresh PBMCs (ex vivo response) from the same calves were analyzed for IFN-γ production, proliferation, and CD4, CD45RO, CD62L, CD44, and CCR7 expression via flow cytometry after overnight stimulation. In response to mycobacterial antigens, ~75% of CD4+ IFN-γ+ cells in long-term cultures expressed a Tcm phenotype while less than 10% of the ex vivo response consisted of Tcm cells. Upon re-exposure to antigen, long-term cultured cells were highly proliferative, a distinctive characteristic of Tcm, and the predominant phenotype within the long-term cultures switched from Tcm to Tem. These findings suggest that proliferative responses of Tcm cells to some extent occurs simultaneously with reversion to effector phenotypes (mostly Tem). The present study characterizes Tcm cells of cattle and their participation in the response to M. bovis infection. PMID:25879774

Enhanced Photoelectrochemical Activity by Autologous Cd/CdO/CdS Heterojunction Photoanodes with High Conductivity and Separation Efficiency.

PubMed

Xie, Shilei; Zhang, Peng; Zhang, Min; Liu, Peng; Li, Wei; Lu, Xihong; Cheng, Faliang; Tong, Yexiang

2017-07-18

The development for hydrogen from solar energy has attracted great attention due to the global demand for clean, environmentally friendly energy. Herein, autologous Cd/CdO/CdS heterojunctions were prepared in a carefully controlled process with metallic Cd as the inner layer and CdO as the interlayer. Further research revealed that the transportation and separation of photogenerated pairs were enhanced due to low resistance of the Cd inner layer and the type II CdO/CdS heterojunction. As a result, the optimized Cd/CdO/CdS heterojunction photoanode showed outstanding and long-term photoelectrochemical activity for water splitting, with a current density of 3.52 mA cm -2 , or a benchmark specific hydrogen production rate of 1.65 μmol cm -2  min -1 at -0.3 V versus Ag/AgCl, by using the environmental pollutants of sulfide and sulfite as sacrificial agents. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Antigen Presenting Properties of a Myeloid Dendritic-Like Cell in Murine Spleen.

PubMed

Hey, Ying-Ying; O'Neill, Helen C

This paper distinguishes a rare subset of myeloid dendritic-like cells found in mouse spleen from conventional (c) dendritic cells (DC) in terms of phenotype, function and gene expression. These cells are tentatively named "L-DC" since they resemble dendritic-like cells produced in longterm cultures of spleen. L-DC can be distinguished on the basis of their unique phenotype as CD11bhiCD11cloMHCII-CD43+Ly6C-Ly6G-Siglec-F- cells. They demonstrate similar ability as cDC to uptake and retain complex antigens like mannan via mannose receptors, but much lower ability to endocytose and retain soluble antigen. While L-DC differ from cDC by their inability to activate CD4+ T cells, they are capable of antigen cross-presentation for activation of CD8+ T cells, although less effectively so than the cDC subsets. In terms of gene expression, CD8- cDC and CD8+ cDC are quite distinct from L-DC. CD8+ cDC are distinguishable from the other two subsets by expression of CD24a, Clec9a, Xcr1 and Tlr11, while CD8- cDC are distinguished by expression of Ccnd1 and H-2Eb2. L-DC are distinct from the two cDC subsets through upregulated expression of Clec4a3, Emr4, Itgam, Csf1r and CD300ld. The L-DC gene profile is quite distinct from that of cDC, confirming a myeloid cell type with distinct antigen presenting properties.

Oxidative stress and antioxidant responses in juvenile Brazilian flounder Paralichthys orbignyanus exposed to sublethal levels of nitrite.

PubMed

Maltez, Lucas Campos; Barbas, Luis André Luz; Nitz, Lilian Fiori; Pellegrin, Lucas; Okamoto, Marcelo Hideo; Sampaio, Luís André; Monserrat, José Maria; Garcia, Luciano

2018-06-01

This study evaluated the effects of short-term exposure to sublethal levels of nitrite on oxidative stress parameters and histology of juvenile Brazilian flounder Paralichthys orbignyanus. An assessment of fish recovery was also performed. Fish were exposed to 0.08 (control), 5.72, 10.43, and 15.27 NO 2 -N mg L -1 for 10 days followed by the same recovery time. Gill, liver, and muscle samples were collected after 1, 5, and 10 days of exposure and after recovery for the measurement of antioxidant capacity against peroxyl radicals (ACAP), glutathione-S-transferase (GST) activity, content of non-protein (NPSH) and protein thiols (PSH), and lipid peroxidation levels by thiobarbituric acid-reactive substances (TBARS) content. Nitrite exposure induced alterations which compromised the overall antioxidant system (reduced ACAP and GST activity) and enhanced oxidative damage in lipids and proteins. Increases in GST activity and NPSH and PSH contents were also demonstrated. The recovery period allowed for resumption of basal levels for all (treatment 5.72 NO 2 -N mg L -1 ) or some of the evaluated parameters (other treatments). In conclusion, exposure to nitrite concentrations from 5.72 to 15.27 NO 2 -N mg L -1 induced oxidative stress and antioxidant responses in juvenile Brazilian flounder. The 10-day recovery period was sufficient for a complete resumption of basal physiological condition of fish exposed to concentrations of up to 5.72 NO 2 -N mg L -1 .

Soil bioretention protects juvenile salmon and their prey from the toxic impacts of urban stormwater runoff.

PubMed

McIntyre, J K; Davis, J W; Hinman, C; Macneale, K H; Anulacion, B F; Scholz, N L; Stark, J D

2015-08-01

Green stormwater infrastructure (GSI), or low impact development, encompasses a diverse and expanding portfolio of strategies to reduce the impacts of stormwater runoff on natural systems. Benchmarks for GSI success are usually framed in terms of hydrology and water chemistry, with reduced flow and loadings of toxic chemical contaminants as primary metrics. Despite the central goal of protecting aquatic species abundance and diversity, the effectiveness of GSI treatments in maintaining diverse assemblages of sensitive aquatic taxa has not been widely evaluated. In the present study we characterized the baseline toxicity of untreated urban runoff from a highway in Seattle, WA, across six storm events. For all storms, first flush runoff was toxic to the daphniid Ceriodaphnia dubia, causing up to 100% mortality or impairing reproduction among survivors. We then evaluated whether soil media used in bioretention, a conventional GSI method, could reduce or eliminate toxicity to juvenile coho salmon (Oncorhynchus kisutch) as well as their macroinvertebrate prey, including cultured C. dubia and wild-collected mayfly nymphs (Baetis spp.). Untreated highway runoff was generally lethal to salmon and invertebrates, and this acute mortality was eliminated when the runoff was filtered through soil media in bioretention columns. Soil treatment also protected against sublethal reproductive toxicity in C. dubia. Thus, a relatively inexpensive GSI technology can be highly effective at reversing the acutely lethal and sublethal effects of urban runoff on multiple aquatic species. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Combined Non-Target Effects of Insecticide and High Temperature on the Parasitoid Bracon nigricans

PubMed Central

Abbes, Khaled; Biondi, Antonio; Kurtulus, Alican; Ricupero, Michele; Russo, Agatino; Siscaro, Gaetano; Chermiti, Brahim; Zappalà, Lucia

2015-01-01

We studied the acute toxicity and the sublethal effects, on reproduction and host-killing activity, of four widely used insecticides on the generalist parasitoid Bracon nigricans (Hymenoptera: Braconidae), a natural enemy of the invasive tomato pest, Tuta absoluta (Lepidoptera: Gelechiidae). Laboratory bioassays were conducted applying maximum insecticide label rates at three constant temperatures, 25, 35 and 40°C, considered as regular, high and very high, respectively. Data on female survival and offspring production were used to calculate population growth indexes as a measure of population recovery after pesticide exposure. Spinetoram caused 80% mortality at 25°C and 100% at higher temperatures, while spinosad caused 100% mortality under all temperature regimes. Cyantraniliprole was slightly toxic to B. nigricans adults in terms of acute toxicity at the three temperatures, while it did not cause any sublethal effects in egg-laying and host-killing activities. The interaction between the two tested factors (insecticide and temperature) significantly influenced the number of eggs laid by the parasitoid, which was the lowest in the case of females exposed to chlorantraniliprole at 35°C. Furthermore, significantly lower B. nigricans demographic growth indexes were estimated for all the insecticides under all temperature conditions, with the exception of chlorantraniliprole at 25°C. Our findings highlight an interaction between high temperatures and insecticide exposure, which suggests a need for including natural stressors, such as temperature, in pesticide risk assessments procedures. PMID:26382245

A Quantitative Comparison of Anti-HIV Gene Therapy Delivered to Hematopoietic Stem Cells versus CD4+ T Cells

PubMed Central

Savkovic, Borislav; Nichols, James; Birkett, Donald; Applegate, Tanya; Ledger, Scott; Symonds, Geoff; Murray, John M.

2014-01-01

Gene therapy represents an alternative and promising anti-HIV modality to highly active antiretroviral therapy. It involves the introduction of a protective gene into a cell, thereby conferring protection against HIV. While clinical trials to date have delivered gene therapy to CD4+T cells or to CD34+ hematopoietic stem cells (HSC), the relative benefits of each of these two cellular targets have not been conclusively determined. In the present analysis, we investigated the relative merits of delivering a dual construct (CCR5 entry inhibitor + C46 fusion inhibitor) to either CD4+T cells or to CD34+ HSC. Using mathematical modelling, we determined the impact of each scenario in terms of total CD4+T cell counts over a 10 year period, and also in terms of inhibition of CCR5 and CXCR4 tropic virus. Our modelling determined that therapy delivery to CD34+ HSC generally resulted in better outcomes than delivery to CD4+T cells. An early one-off therapy delivery to CD34+ HSC, assuming that 20% of CD34+ HSC in the bone marrow were gene-modified (G+), resulted in total CD4+T cell counts ≥180 cells/ µL in peripheral blood after 10 years. If the uninfected G+ CD4+T cells (in addition to exhibiting lower likelihood of becoming productively infected) also exhibited reduced levels of bystander apoptosis (92.5% reduction) over non gene-modified (G-) CD4+T cells, then total CD4+T cell counts of ≥350 cells/ µL were observed after 10 years, even if initially only 10% of CD34+ HSC in the bone marrow received the protective gene. Taken together our results indicate that: 1.) therapy delivery to CD34+ HSC will result in better outcomes than delivery to CD4+T cells, and 2.) a greater impact of gene therapy will be observed if G+ CD4+T cells exhibit reduced levels of bystander apoptosis over G- CD4+T cells. PMID:24945407

Conventional CD4+ T cells present bacterial antigens to induce cytotoxic and memory CD8+ T cell responses.

PubMed

Cruz-Adalia, Aránzazu; Ramirez-Santiago, Guillermo; Osuna-Pérez, Jesús; Torres-Torresano, Mónica; Zorita, Virgina; Martínez-Riaño, Ana; Boccasavia, Viola; Borroto, Aldo; Martínez Del Hoyo, Gloria; González-Granado, José María; Alarcón, Balbino; Sánchez-Madrid, Francisco; Veiga, Esteban

2017-11-17

Bacterial phagocytosis and antigen cross-presentation to activate CD8 + T cells are principal functions of professional antigen presenting cells. However, conventional CD4 + T cells also capture and kill bacteria from infected dendritic cells in a process termed transphagocytosis (also known as transinfection). Here, we show that transphagocytic T cells present bacterial antigens to naive CD8 + T cells, which proliferate and become cytotoxic in response. CD4 + T-cell-mediated antigen presentation also occurs in vivo in the course of infection, and induces the generation of central memory CD8 + T cells with low PD-1 expression. Moreover, transphagocytic CD4 + T cells induce protective anti-tumour immune responses by priming CD8 + T cells, highlighting the potential of CD4 + T cells as a tool for cancer immunotherapy.

Subclinical HSV-1 infections provide site-specific resistance to an unrelated pathogen

PubMed Central

Rowe, Alexander M.; Yun, Hongming; Treat, Benjamin R.; Kinchington, Paul R.; Hendricks, Robert L.

2016-01-01

Herpes Simplex Virus-1 (HSV-1) infections of the cornea range in severity from minor transient discomfort to the blinding disease Herpes Stromal Keratitis (HSK), yet most patients experience a single episode of epithelial keratitis followed by reestablishment of a clear cornea. We asked if a single transient episode of HSV-1 epithelial keratitis causes long-term changes in the corneal microenvironment that influence immune responses to subsequent corneal infection or trauma. We showed that C57BL/6 mouse corneas infected with HSV-1 KOS, which induces transient herpes epithelial keratitis without HSK sequelae, possessed a significant leukocytic infiltrate comprised primarily of CD4+ T cells and macrophages along with elevated chemokines and cytokines that persisted without loss of corneal clarity (subclinical inflammation). Chemokine and cytokine expression was CD4+T cell-dependent, in that their production was significantly reduced by systemic CD4+T cell depletion starting before infection, although short-term (3 day) local CD4+ T cell depletion after infection did not influence chemokine levels in cornea. Corneas with subclinical inflammation developed significantly greater trauma-induced inflammation when they were recipients of syngeneic corneal transplants, but also exhibited significantly increased resistance to infections by unrelated pathogens such as pseudorabies virus (PRV). The resistance to PRV was CD4+ T cell-dependent, since it was eliminated by local CD4+T cell-depletion from the cornea. We conclude that transient HSV-1 corneal infections cause long-term alterations of the corneal microenvironment that provide CD4-dependent innate resistance to subsequent infections by antigenically unrelated pathogens. PMID:28062697

Intracoronary injection of CD34-cells in chronic ischemic heart failure: 7 years follow-up of the DanCell study.

PubMed

Hansen, Morten; Nyby, Sebastian; Eifer Møller, Jacob; Videbæk, Lars; Kassem, Moustapha; Barington, Torben; Thayssen, Per; Diederichsen, Axel Cosmus Pyndt

2014-01-01

Seven years ago, the DanCell study was carried out to test the hypothesis of improvement in left ventricular ejection fraction (LVEF) following repeated intracoronary injections of autologous bone marrow-derived stem cells (BMSCs) in patients suffering from chronic ischemic heart failure. In this post hoc analysis, the long-term effect of therapy is assessed. 32 patients [mean age 61 (SD ± 9), 81% males] with systolic dysfunction (LVEF 33 ± 9%) received two repeated intracoronary infusions (4 months apart) of autologous BMSCs (1,533 ± 765 × 10(6) BMSCs including 23 ± 11 × 10(6) CD34(+) cells and 14 ± 7 × 10(6) CD133(+) cells). Patients were followed for 7 years and deaths were recorded. During follow-up, 10 patients died (31%). In univariate regression analysis, the total number of BMSCs, CD34(+) cell count and CD133(+) cell count did not significantly correlate with survival (hazard ratio: 0.999, 95% CI: 0.998-1.000, p = 0.24; hazard ratio: 0.94, 95% CI: 0.88-1.01, p = 0.10, and hazard ratio: 0.96, 95% CI: 0.87-1.07, p = 0.47, respectively). After adjustment for baseline variables in multivariate regression analysis, the CD34(+) cell count was significantly associated with survival (hazard ratio: 0.90, 95% CI: 0.82-1.00, p = 0.04). Intracoronary injections of a high number of CD34(+) cells may have a beneficial effect on chronic ischemic heart failure in terms of long-term survival.

Spatial variability of soil total and DTPA-extractable cadmium caused by long-term application of phosphate fertilizers, crop rotation, and soil characteristics.

PubMed

Jafarnejadi, A R; Sayyad, Gh; Homaee, M; Davamei, A H

2013-05-01

Increasing cadmium (Cd) accumulation in agricultural soils is undesirable due to its hazardous influences on human health. Thus, having more information on spatial variability of Cd and factors effective to increase its content on the cultivated soils is very important. Phosphate fertilizers are main contamination source of cadmium (Cd) in cultivated soils. Also, crop rotation is a critical management practice which can alter soil Cd content. This study was conducted to evaluate the effects of long-term consumption of the phosphate fertilizers, crop rotations, and soil characteristics on spatial variability of two soil Cd species (i.e., total and diethylene triamine pentaacetic acid (DTPA) extractable) in agricultural soils. The study was conducted in wheat farms of Khuzestan Province, Iran. Long-term (27-year period (1980 to 2006)) data including the rate and the type of phosphate fertilizers application, the respective area, and the rotation type of different regions were used. Afterwards, soil Cd content (total or DTPA extractable) and its spatial variability in study area (400,000 ha) were determined by sampling from soils of 255 fields. The results showed that the consumption rate of di-ammonium phosphate fertilizer have been varied enormously in the period study. The application rate of phosphorus fertilizers was very high in some subregions with have extensive agricultural activities (more than 95 kg/ha). The average and maximum contents of total Cd in the study region were obtained as 1.47 and 2.19 mg/kg and DTPA-extractable Cd as 0.084 and 0.35 mg/kg, respectively. The spatial variability of Cd indicated that total and DTPA-extractable Cd contents were over 0.8 and 0.1 mg/kg in 95 and 25 % of samples, respectively. The spherical model enjoys the best fitting and lowest error rate to appraise the Cd content. Comparing the phosphate fertilizer consumption rate with spatial variability of the soil cadmium (both total and DTPA extractable) revealed the high correlation between the consumption rate of P fertilizers and soil Cd content. Rotation type was likely the main effective factor on variations of the soil DTPA-extractable Cd contents in some parts (eastern part of study region) and could explain some Cd variation. Total Cd concentrations had significant correlation with the total neutralizing value (p < 0.01), available P (p < 0.01), cation exchange capacity (p < 0.05), and organic carbon (p < 0.05) variables. The DTPA-extractable Cd had significant correlation with OC (p < 0.01), pH, and clay content (p < 0.05). Therefore, consumption rate of the phosphate fertilizers and crop rotation are important factors on solubility and hence spatial variability of Cd content in agricultural soils.

The Risk of Relapse after Anti-TNF Discontinuation in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis.

PubMed

Gisbert, Javier P; Marín, Alicia C; Chaparro, María

2016-05-01

To perform a meta-analysis of the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC), to evaluate risk factors for relapse, and to assess the response to retreatment with the same anti-TNF. Studies evaluating the incidence of relapse after anti-TNF discontinuation in patients with CD or UC who reached clinical remission with anti-TNFs were included. Bibliographies up to January 2015 were searched. Frequency of relapse after discontinuation of anti-TNF agents was determined; meta-analyses were performed using the inverse-variance method. We included 27 studies (21 infliximab and 6 infliximab/adalimumab). The overall risk of relapse after discontinuation of anti-TNF therapy was 44% for CD (95% confidence interval (CI) 36-51%; I(2)=79%; 912 patients) and 38% for UC (23-52%; I(2)=82%; 266 patients). In CD, the relapse rate was 38% at 6 months after discontinuation (short term), 40% at 12 months (medium term), and 49% at >25 months (long term). In UC, 28% of patients relapsed at 12 months. In CD, when clinical remission was the only criterion for stopping anti-TNF therapy, the relapse rate after 1 year was 42%, which decreased to 26% when endoscopic remission was also required. Retreatment with the same anti-TNF induced remission again in 80% of cases (68-91%). Approximately one-third of patients with inflammatory bowel disease in remission under anti-TNF treatment relapsed 1 year after discontinuation. This proportion increased to half in the long term. In CD patients, the risk of relapse was lower when the criterion for discontinuation was endoscopic remission and not only clinical remission. Response to retreatment with the same anti-TNF agent was favorable.

Bacterial sulfite dehydrogenases in organotrophic metabolism: separation and identification in Cupriavidus necator H16 and in Delftia acidovorans SPH-1.

PubMed

Denger, Karin; Weinitschke, Sonja; Smits, Theo H M; Schleheck, David; Cook, Alasdair M

2008-01-01

The utilization of organosulfonates as carbon sources by aerobic or nitrate-reducing bacteria usually involves a measurable, uncharacterized sulfite dehydrogenase. This is tacitly assumed to be sulfite : ferricytochrome-c oxidoreductase [EC 1.8.2.1], despite negligible interaction with (eukaryotic) cytochrome c: the enzyme is assayed at high specific activity with ferricyanide as electron acceptor. Purified periplasmic sulfite dehydrogenases (SorAB, SoxCD) are known from chemoautotrophic growth and are termed 'sulfite oxidases' by bioinformatic services. The catalytic unit (SorA, SoxC; termed 'sulfite oxidases' cd02114 and cd02113, respectively) binds a molybdenum-cofactor (Moco), and involves a cytochrome c (SorB, SoxD) as electron acceptor. The genomes of several bacteria that express a sulfite dehydrogenase during heterotrophic growth contain neither sorAB nor soxCD genes; others contain at least four paralogues, for example Cupriavidus necator H16, which is known to express an inducible sulfite dehydrogenase during growth with taurine (2-aminoethanesulfonate). This soluble enzyme was enriched 320-fold in four steps. The 40 kDa protein (denatured) had an N-terminal amino acid sequence which started at position 42 of the deduced sequence of H16_B0860 (termed 'sulfite oxidase' cd02114), which we named SorA. The neighbouring gene is an orthologue of sorB, and the sorAB genes were co-transcribed. Cell fractionation showed SorA to be periplasmic. The corresponding enzyme in Delftia acidovorans SPH-1 was enriched 270-fold, identified as Daci_0055 (termed 'sulfite oxidase' cd02110) and has a cytochrome c encoded downstream. We presume, from genomic data for bacteria and archaea, that there are several subgroups of sulfite dehydrogenases, which all contain a Moco, and transfer electrons to a specific cytochrome c.

Neonatal Desensitization Supports Long-Term Survival and Functional Integration of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells in Rat Joint Cartilage Without Immunosuppression

PubMed Central

Zhang, Shufang; Jiang, Yang Zi; Zhang, Wei; Chen, Longkun; Tong, Tong; Liu, Wanlu; Mu, Qin; Liu, Hua; Ji, Junfeng; Ouyang, Hong Wei

2013-01-01

Immunological response hampers the investigation of human embryonic stem cells (hESCs) or their derivates for tissue regeneration in vivo. Immunosuppression is often used after surgery, but exhibits side effects of significant weight loss and allows only short-term observation. The purpose of this study was to investigate whether neonatal desensitization supports relative long-term survival of hESC-derived mesenchymal stem cells (hESC-MSCs) and promotes cartilage regeneration. hESC-MSCs were injected on the day of birth in rats. Six weeks after neonatal injection, a full-thickness cylindrical cartilage defect was created and transplanted with a hESC-MSC-seeded collagen bilayer scaffold (group d+s+c) or a collagen bilayer scaffold (group d+s). Rats without neonatal injection were transplanted with the hESC-MSC-seeded collagen bilayer scaffold to serve as controls (group s+c). Cartilage regeneration was evaluated by histological analysis, immunohistochemical staining, and biomechanical test. The role of hESC-MSCs in cartilage regeneration was analyzed by CD4 immunostaining, cell death detection, and visualization of human cells in regenerated tissues. hESC-MSCs expressed CD105, CD73, CD90, CD29, and CD44, but not CD45 and CD34, and possessed trilineage differentiation potential. Group d+s+c exhibited greater International Cartilage Repair Society (ICRS) scores than group d+s or group s+c. Abundant collagen type II and improved mechanical properties were detected in group d+s+c. There were less CD4+ inflammatory cell infiltration and cell death at week 1, and hESC-MSCs were found to survive as long as 8 weeks after transplantation in group d+s+c. Our study suggests that neonatal desensitization before transplantation may be an efficient way to develop a powerful tool for preclinical study of human cell-based therapies in animal models. PMID:22788986

Neonatal desensitization supports long-term survival and functional integration of human embryonic stem cell-derived mesenchymal stem cells in rat joint cartilage without immunosuppression.

PubMed

Zhang, Shufang; Jiang, Yang Zi; Zhang, Wei; Chen, Longkun; Tong, Tong; Liu, Wanlu; Mu, Qin; Liu, Hua; Ji, Junfeng; Ouyang, Hong Wei; Zou, Xiaohui

2013-01-01

Immunological response hampers the investigation of human embryonic stem cells (hESCs) or their derivates for tissue regeneration in vivo. Immunosuppression is often used after surgery, but exhibits side effects of significant weight loss and allows only short-term observation. The purpose of this study was to investigate whether neonatal desensitization supports relative long-term survival of hESC-derived mesenchymal stem cells (hESC-MSCs) and promotes cartilage regeneration. hESC-MSCs were injected on the day of birth in rats. Six weeks after neonatal injection, a full-thickness cylindrical cartilage defect was created and transplanted with a hESC-MSC-seeded collagen bilayer scaffold (group d+s+c) or a collagen bilayer scaffold (group d+s). Rats without neonatal injection were transplanted with the hESC-MSC-seeded collagen bilayer scaffold to serve as controls (group s+c). Cartilage regeneration was evaluated by histological analysis, immunohistochemical staining, and biomechanical test. The role of hESC-MSCs in cartilage regeneration was analyzed by CD4 immunostaining, cell death detection, and visualization of human cells in regenerated tissues. hESC-MSCs expressed CD105, CD73, CD90, CD29, and CD44, but not CD45 and CD34, and possessed trilineage differentiation potential. Group d+s+c exhibited greater International Cartilage Repair Society (ICRS) scores than group d+s or group s+c. Abundant collagen type II and improved mechanical properties were detected in group d+s+c. There were less CD4+ inflammatory cell infiltration and cell death at week 1, and hESC-MSCs were found to survive as long as 8 weeks after transplantation in group d+s+c. Our study suggests that neonatal desensitization before transplantation may be an efficient way to develop a powerful tool for preclinical study of human cell-based therapies in animal models.

Lethal and sublethal effects of marine sediment extracts on fish cells and chromosomes

NASA Astrophysics Data System (ADS)

Landolt, Marsha L.; Kocan, Richard M.

1984-03-01

The cost of conducting conventional chronic bioassays with every potentially toxic compound found in marine ecosystems is prohibitive; therefore short-term toxicity tests which can be used for rapid screening were developed. The tests employ cultured fish cells to measure lethal, sublethal or genotoxic effects of pure compounds and complex mixtures. The sensitivity of these tests has been proven under laboratory conditions; the following study used two of these tests, the anaphase aberration test and a cytotoxicity assay, under field conditions. Sediment was collected from 97 stations within Puget Sound, Washington. Serial washings of the sediment in methanol and dichloromethane yielded an organic extract which was dried, dissolved in DMSO and incubated as a series of dilutions with rainbow trout gonad (RTG-2) cells. The toxic effects of the extract were measured by examining the rate of cell proliferation and the percentage of damaged anaphase figures. Anaphase figures were considered to be abnormal if they exhibited non-disjunctions, chromosome fragments, or chromosome bridges. A second cell line (bluegill fry, BF-2) was also tested for cell proliferation and was included because, unlike the RTG-2 cell line, it contains little or no mixed function oxygenase activity. Of 97 stations tested, 35 showed no genotoxic activity, 42 showed high genotoxic activity (P≤.01) and the remainder were intermediate. Among the toxic sites were several deep water stations adjacent to municipal sewage outfalls and four urban waterways contaminated by industrial and municipal effluents. Extracts from areas that showed genotoxic effects also inhibited cell proliferation and were cytotoxic to RTG-2 cells. Few effects were noted in the MFO deficient BF-2 cells. Short term in vitro tests provide aquatic toxicologists with a versatile and cost effective tool for screening complex environments. Through these tests one can identify compounds or geographic regions that exhibit high cytotoxic or genotoxic potential.

Long-term survival in HIV positive patients with up to 15 Years of antiretroviral therapy.

PubMed

McManus, Hamish; O'Connor, Catherine C; Boyd, Mark; Broom, Jennifer; Russell, Darren; Watson, Kerrie; Roth, Norman; Read, Phillip J; Petoumenos, Kathy; Law, Matthew G

2012-01-01

Life expectancy has increased for newly diagnosed HIV patients since the inception of combination antiretroviral treatment (cART), but there remains a need to better understand the characteristics of long-term survival in HIV-positive patients. We examined long-term survival in HIV-positive patients receiving cART in the Australian HIV Observational Database (AHOD), to describe changes in mortality compared to the general population and to develop longer-term survival models. Data were examined from 2,675 HIV-positive participants in AHOD who started cART. Standardised mortality ratios (SMR) were calculated by age, sex and calendar year across prognostic characteristics using Australian Bureau of Statistics national data as reference. SMRs were examined by years of duration of cART by CD4 and similarly by viral load. Survival was analysed using Cox-proportional hazards and parametric survival models. The overall SMR for all-cause mortality was 3.5 (95% CI: 3.0-4.0). SMRs by CD4 count were 8.6 (95% CI: 7.2-10.2) for CD4<350 cells/µl; 2.1 (95% CI: 1.5-2.9) for CD4 = 350-499 cells/µl; and 1.5 (95% CI: 1.1-2.0) for CD4≥500 cells/µl. SMRs for patients with CD4 counts <350 cells/µL were much higher than for patients with higher CD4 counts across all durations of cART. SMRs for patients with viral loads greater than 400 copies/ml were much higher across all durations of cART. Multivariate models demonstrated improved survival associated with increased recent CD4, reduced recent viral load, younger patients, absence of HBVsAg-positive ever, year of HIV diagnosis and incidence of ADI. Parametric models showed a fairly constant mortality risk by year of cART up to 15 years of treatment. Observed mortality remained fairly constant by duration of cART and was modelled accurately by accepted prognostic factors. These rates did not vary much by duration of treatment. Changes in mortality with age were similar to those in the Australian general population.

Long-Term Survival in HIV Positive Patients with up to 15 Years of Antiretroviral Therapy

PubMed Central

McManus, Hamish; O'Connor, Catherine C.; Boyd, Mark; Broom, Jennifer; Russell, Darren; Watson, Kerrie; Roth, Norman; Read, Phillip J.; Petoumenos, Kathy; Law, Matthew G.

2012-01-01

Background Life expectancy has increased for newly diagnosed HIV patients since the inception of combination antiretroviral treatment (cART), but there remains a need to better understand the characteristics of long-term survival in HIV-positive patients. We examined long-term survival in HIV-positive patients receiving cART in the Australian HIV Observational Database (AHOD), to describe changes in mortality compared to the general population and to develop longer-term survival models. Methods Data were examined from 2,675 HIV-positive participants in AHOD who started cART. Standardised mortality ratios (SMR) were calculated by age, sex and calendar year across prognostic characteristics using Australian Bureau of Statistics national data as reference. SMRs were examined by years of duration of cART by CD4 and similarly by viral load. Survival was analysed using Cox-proportional hazards and parametric survival models. Results The overall SMR for all-cause mortality was 3.5 (95% CI: 3.0–4.0). SMRs by CD4 count were 8.6 (95% CI: 7.2–10.2) for CD4<350 cells/µl; 2.1 (95% CI: 1.5–2.9) for CD4 = 350–499 cells/µl; and 1.5 (95% CI: 1.1–2.0) for CD4≥500 cells/µl. SMRs for patients with CD4 counts <350 cells/µL were much higher than for patients with higher CD4 counts across all durations of cART. SMRs for patients with viral loads greater than 400 copies/ml were much higher across all durations of cART. Multivariate models demonstrated improved survival associated with increased recent CD4, reduced recent viral load, younger patients, absence of HBVsAg-positive ever, year of HIV diagnosis and incidence of ADI. Parametric models showed a fairly constant mortality risk by year of cART up to 15 years of treatment. Conclusion Observed mortality remained fairly constant by duration of cART and was modelled accurately by accepted prognostic factors. These rates did not vary much by duration of treatment. Changes in mortality with age were similar to those in the Australian general population. PMID:23144991

Short-term cadmium exposure induces gas exchanges, morphological and ultrastructural disturbances in mangrove Avicennia schaueriana young plants.

PubMed

Garcia, Janaina S; Dalmolin, Ândrea C; Cortez, Priscila A; Barbeira, Paulo S; Mangabeira, Pedro A O; França, Marcel G C

2018-06-01

Mangroves have been subject to more metal contamination, including cadmium (Cd). This study evaluated if a relatively short Cd exposure may induce metabolic, morphological and ultrastructural cell disturbance in Avicennia schaueriana. Cd induced evident constraints to seedlings since there was reduction in leaf gas exchanges and the plants did not survive for more than 10 days at a higher Cd exposure in controlled conditions. The highest Cd accumulation was observed in roots and gradually less in stem and leaves. Cadmium induced lignin deposition was observed in xylem cells of all vegetative organs. Intense sclerification in xylem cells, endoderm and change in the hypoderm organization were also detected. Cadmium clearly induced chloroplast deformities with ruptures of its membranes, thylakoids and core and provoked cytoplasm disorganization. These metal constraints under natural conditions for long term can lead to the accumulation of cellular and metabolic damages and jeopardize seedlings establishment and local biodiversity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Chronic Exposure to Tributyltin Induces Brain Functional Damage in Juvenile Common Carp (Cyprinus carpio)

PubMed Central

Li, Zhi-Hua; Li, Ping; Shi, Ze-Chao

2015-01-01

The aim of the present study was to investigate the effect of Tributyltin (TBT) on brain function and neurotoxicity of freshwater teleost. The effects of long-term exposure to TBT on antioxidant related indices (MDA, malondialdehyde; SOD, superoxide dismutase; CAT, catalase; GR, glutathione reductase; GPx, glutathione peroxidase), Na+-K+-ATPase and neurological parameters (AChE, acetylcholinesterase; MAO, monoamine oxidase; NO, nitric oxide) in the brain of common carp were evaluated. Fish were exposed to sublethal concentrations of TBT (75 ng/L, 0.75 μg/L and 7.5 μg/L) for 15, 30, and 60 days. Based on the results, a low level and short-term TBT-induced stress could not induce the notable responses of the fish brain, but long-term exposure (more than 15 days) to TBT could lead to obvious physiological-biochemical responses (based on the measured parameters). The results also strongly indicated that neurotoxicity of TBT to fish. Thus, the measured physiological responses in fish brain could provide useful information to better understand the mechanisms of TBT-induced bio-toxicity. PMID:25879203

Chronic exposure to Tributyltin induces brain functional damage in juvenile common carp (Cyprinus carpio).

PubMed

Li, Zhi-Hua; Li, Ping; Shi, Ze-Chao

2015-01-01

The aim of the present study was to investigate the effect of Tributyltin (TBT) on brain function and neurotoxicity of freshwater teleost. The effects of long-term exposure to TBT on antioxidant related indices (MDA, malondialdehyde; SOD, superoxide dismutase; CAT, catalase; GR, glutathione reductase; GPx, glutathione peroxidase), Na+-K+-ATPase and neurological parameters (AChE, acetylcholinesterase; MAO, monoamine oxidase; NO, nitric oxide) in the brain of common carp were evaluated. Fish were exposed to sublethal concentrations of TBT (75 ng/L, 0.75 μg/L and 7.5 μg/L) for 15, 30, and 60 days. Based on the results, a low level and short-term TBT-induced stress could not induce the notable responses of the fish brain, but long-term exposure (more than 15 days) to TBT could lead to obvious physiological-biochemical responses (based on the measured parameters). The results also strongly indicated that neurotoxicity of TBT to fish. Thus, the measured physiological responses in fish brain could provide useful information to better understand the mechanisms of TBT-induced bio-toxicity.

Sublethal Effects of ActiveGuard Exposure on Feeding Behavior and Fecundity of the Bed Bug (Hemiptera: Cimicidae).

PubMed

Jones, Susan C; Bryant, Joshua L; Sivakoff, Frances S

2015-05-01

Sublethal exposure to pesticides can alter insect behavior with potential for population-level consequences. We investigated sublethal effects of ActiveGuard, a permethrin-impregnated fabric, on feeding behavior and fecundity of bed bugs (Cimex lectularius L.) from five populations that ranged from susceptible to highly pyrethroid resistant. After exposure to ActiveGuard fabric or untreated fabric for 1 or 10 min, adult virgin female bed bugs were individually observed when offered a blood meal to determine feeding attempts and weight gain. Because bed bug feeding behavior is tightly coupled with its fecundity, all females were then mated, and the number of eggs laid and egg hatch rate were used as fecundity measures. We observed that pyrethroid-resistant and -susceptible bugs were not significantly different for all feeding and fecundity parameters. Bed bugs exposed to ActiveGuard for 10 min were significantly less likely to attempt to feed or successfully feed, and their average blood meal size was significantly smaller compared with individuals in all other groups. Independent of whether or not feeding occurred, females exposed to ActiveGuard for 10 min were significantly more likely to lay no eggs. Only a single female exposed to ActiveGuard for 10 min laid any eggs. Among the other fabric treatment-exposure time groups, there were no observable differences in egg numbers or hatch rates. Brief exposure of 10 min to ActiveGuard fabric appeared to decrease feeding and fecundity of pyrethroid-resistant and susceptible bed bugs, suggesting the potentially important role of sublethal exposure for the control of this ectoparasitic insect. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Sublethal effects of four insecticides on folding and spinning behavior in the rice leaffolder, Cnaphalocrocis medinalis (Guenée) (Lepidoptera: Pyralidae).

PubMed

Yang, Yajun; Wang, Caiyun; Xu, Hongxing; Lu, Zhongxian

2018-03-01

The rice leaffolder, Cnaphalocrocis medinalis, is an important rice pest. The sublethal effects of chlorpyrifos, chlorantraniliprole, emamectin benzoate and spinosad were investigated on the folding and spinning behaviors of third- to fifth-instar C. medinalis larvae (L3 - L5) after insecticidal exposure of the second instar. A 25% lethal concentration (LC 25 ) of chlorpyrifos prolonged the leaf selection time of L5, and reduced the number of binds per primary fold for L4 and L5. An LC 10 of chlorantraniliprole reduced the number of binds per primary fold for L4 and increased the number of head swings per bind for L5. An LC 10 of emamectin benzoate shortened the primary fold length for L5 and decreased the number of head swings per primary fold for L3 and L4 and the number of head swings per bind for L3, while an LC 25 of emamectin benzoate shortened the fold length per 24 h for L5 and folding time for L3. An LC 10 of spinosad lowered the fold length per 24 h and the number of head swings for L5. An LC 25 of spinosad prolonged leaf selection time, and decreased primary fold length, binds per primary fold, binds per fold and fold length per 24 h in L5. Emamectin benzoate and spinosad exerted stronger sublethal effects on the folding and spinning behavior of C. medinalis than chlorpyrifos and chlorantraniliprole. These results provide better understanding of the sublethal effects of interactions of insecticides on C. medinalis. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Lethal and sublethal toxicity of the industrial chemical epichlorohydrin on Rhinella arenarum (Anura, Bufonidae) embryos and larvae.

PubMed

Hutler Wolkowicz, Ianina R; Aronzon, Carolina M; Pérez Coll, Cristina S

2013-12-15

Lethal and sublethal toxicity of the major chemical used in epoxide compounds, epichlorohydrin (ECH) was evaluated on the early life cycle of the common South American toad, Rhinella arenarum (Anura, Bufonidae). The stages evaluated were (according to Del Conte and Sirlin): early blastula (S.3-S.4), gastrula (S.10-S.12), rotation (S.15), tail bud (S.17), muscular response (S.18), gill circulation (S.20), open mouth (S.21), opercular folds (S.23) and complete operculum (S.25). The LC50 and EC50 values for lethal and sublethal effects were calculated. The early blastula was the most sensitive stage to ECH both for continuously and pulse-exposures (LC50-24h=50.9 mg L(-1)), while S.20 was the most resistant (LC50-24h=104.9 mg L(-1)). Among sublethal effects, early blastula was also the most sensitive stage (LOEC-48 h=20 mg L(-1)) and it has a Teratogenic Index of 2.5, which indicates the teratogenic potential of the substance. The main abnormalities were persistent yolk plugs, cell dissociation, tumors, hydropsy, oral malformations, axial/tail flexures, delayed development and reduced body size. ECH also caused neurotoxicity including scarce response to stimuli, reduction in the food intake, general weakness, spasms and shortening, erratic or circular swimming. Industrial contamination is considered an important factor on the decline of amphibian populations. Considering the available information about ECH's toxicity and its potential hazard to the environment, this work shows the first results of its developmental toxicity on a native amphibian species, Rhinella arenarum. Copyright © 2013 Elsevier B.V. All rights reserved.

[Sublethal effects of spinetoram and azadirachtin on development and reproduction of Frankliniella occidentalis (Pergande).

PubMed

Yang, Guang Ming; Zhi, Jun Rui; Li, Shun Xin; Liu, Li

2016-11-18

To evaluate the sublethal effects of spinetoram and azadirachtin on western flower thrips, Frankliniella occidentalis, leaf dipping method was used to determine their sublethal concentrations (LC 25 ) on the 2 nd instar nymph, and their influences on development and reproduction of F. occidentalis were studied. The results showed exposure of sublethal concentrations of spinetoram and azadirachtin to F. accidentalis had different degrees of effects on this insect pest. Under bisexual reproduction, the LC 25 spinetoram had no significant influences on pre-oviposition period, female adult longevity and fecundity, but male adult longevity was significantly shorter than the control. The LC 25 azadirachtin significantly reduced fecundity and prolonged pre-oviposition period. Under parthenogenesis, the LC 25 spinetoram and azadirachtin extended the pre-oviposition duration, whereas the LC 25 azadirachtin shortened the female adult longevity and significantly decreased fecundity. The LC 25 spinetoram and azadirachtin had different influences on developmental duration of each stage of next generation. The immature stage in treatment group of the LC 25 spinetoram was shorter than that in treatment group of the LC 25 azadirachtin, under bisexual reproduction or parthenogenesis. Intrinsic rate of increase (r m ) and finite rate of increase (λ) of population treated by the LC 25 spinetoram were higher than those of the control, whereas the r m , R 0 , and λ of population treated by the LC 25 azadirachtin were lower than those of the control. The findings indicated that the effects of the LC 25 spinetoram and azadirachtin on the development and reproduction of F. accidentalis were different. The LC 25 spinetoram had certain stimulating effect, whereas the LC 25 azadirach-tinon had significant inhibitory effect. Two biopesticides' influences were related with the reproductive patterns of F. accidentalis.

Fast screening of Bifidobacterium longum sublethal stress conditions in a novel two-stage continuous culture strategy.

PubMed

Mozzetti, V; Grattepanche, F; Berger, B; Rezzonico, E; Arigoni, F; Lacroix, C

2013-06-01

A central issue in the application of probiotics as food additives is their fastidious production and their sensitivity to many environmental stresses. The importance of inducible cell-protective mechanisms triggered by application of sublethal stresses for survival under stress conditions has been demonstrated. Continuous cultures could be a suitable and more efficient method to test stress factors on one culture instead of several repeated batch cultures. In this study, the application of a two-stage continuous culture of Bifidobacterium longum NCC2705 was investigated. The first reactor was operated under fixed conditions at 37 °C and pH 6.0 and used to produce cells with controlled physiology, mimicking cells in the late exponential growth phase. Stress pretreatment combinations of pH (6.0, 5.0 and 4.0), temperature (37, 45 and 47 °C) and NaCl (0, 5 and 10%) were tested in the second reactor. Of all tested combinations, only those of pH 4.0 significantly decreased cell viability in the second reactor compared to control conditions (37 °C, pH 6.0, 0% NaCl) and, therefore, could not be considered as sublethal stresses. Pretreatments with 5 or 10% NaCl had a negative effect on cell viability after gastric lethal stress. A significant improvement in cell resistance to heat lethal stress (56 °C, 5 min) was observed for cells pretreated at 47 °C. In contrast, heat pretreatment negatively affected cell viability after freeze drying and osmotic lethal stresses. The two-stage continuous culture allowed for efficient screening of several stress pretreatments during the same experiment with up to four different conditions tested per day. Optimal sublethal stress conditions can also be applied for producing cells with traditional batch cultures.

Sublethal red tide toxin exposure in free-ranging manatees (Trichechus manatus) affects the immune system through reduced lymphocyte proliferation responses, inflammation, and oxidative stress.

PubMed

Walsh, Catherine J; Butawan, Matthew; Yordy, Jennifer; Ball, Ray; Flewelling, Leanne; de Wit, Martine; Bonde, Robert K

2015-04-01

The health of many Florida manatees (Trichechus manatus latirostris) is adversely affected by exposure to blooms of the toxic dinoflagellate, Karenia brevis. K. brevis blooms are common in manatee habitats of Florida's southwestern coast and produce a group of cyclic polyether toxins collectively referred to as red tide toxins, or brevetoxins. Although a large number of manatees exposed to significant levels of red tide toxins die, several manatees are rescued from sublethal exposure and are successfully treated and returned to the wild. Sublethal brevetoxin exposure may potentially impact the manatee immune system. Lymphocyte proliferative responses and a suite of immune function parameters in the plasma were used to evaluate effects of brevetoxin exposure on health of manatees rescued from natural exposure to red tide toxins in their habitat. Blood samples were collected from rescued manatees at Lowry Park Zoo in Tampa, FL and from healthy, unexposed manatees in Crystal River, FL. Peripheral blood leukocytes (PBL) isolated from whole blood were stimulated with T-cell mitogens, ConA and PHA. A suite of plasma parameters, including plasma protein electrophoresis profiles, lysozyme activity, superoxide dismutase (SOD) activity, and reactive oxygen/nitrogen (ROS/RNS) species, was also used to assess manatee health. Significant decreases (p<0.05) in lymphocyte proliferation were observed in ConA and PHA stimulated lymphocytes from rescued animals compared to non-exposed animals. Significant correlations were observed between oxidative stress markers (SOD, ROS/RNS) and plasma brevetoxin concentrations. Sublethal exposure to brevetoxins in the wild impacts some immune function components, and thus, overall health, in the Florida manatee. Copyright © 2015 Elsevier B.V. All rights reserved.

BCR-crosslinking induces a transcription of protein phosphatase component G5PR that is required for mature B-cell survival

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huq Ronny, Faisal Mahmudul; Igarashi, Hideya; Core Research for Evolutional Science and Technology

2006-02-03

BCR-crosslinking triggers activation-induced cell death (AICD) selectively in the restricted stage of B-cell differentiation. We examined the transcription of a protein phosphatase subunit G5PR in immature and mature B-cells, because absence of this factor augmented cell sensitivity to AICD, associated with increased activation of JNK and Bim. BCR-crosslinking-induced G5pr transcription in AICD-resistant mature splenic IgM{sup lo}IgD{sup hi} B-cells but not in AICD susceptible immature IgM{sup hi}IgD{sup lo} B-cells. Thus, G5pr induction correlated with the prevention of AICD; High in mature splenic CD23{sup hi} B-cells but low in immature B-cells of neonatal mice, sub-lethally irradiated mice, or xid mice. Lack ofmore » G5pr upregulation was associated with the prolonged activation of JNK. The G5pr cDNA transfection protected an immature B-cell line WEHI-231 from BCR-mediated AICD. The differential expression of G5PR might be responsible for the antigen-dependent selection of B-cells.« less

Clinical and economic outcomes in a population-based European cohort of 948 ulcerative colitis and Crohn's disease patients by Markov analysis.

PubMed

Odes, S; Vardi, H; Friger, M; Esser, D; Wolters, F; Moum, B; Waters, H; Elkjaer, M; Bernklev, T; Tsianos, E; O'Morain, C; Stockbrügger, R; Munkholm, P; Langholz, E

2010-04-01

Forecasting clinical and economic outcomes in ulcerative colitis (UC) and Crohn's disease (CD) patients is complex, but necessary. To determine: the frequency of treatment-classified clinical states; the probability of transition between states; and the economic outcomes. Newly diagnosed UC and CD patients, allocated into seven clinical states by medical and surgical treatments recorded in serial 3-month cycles, underwent Markov analysis. Over 10 years, 630 UC and 318 CD patients had 22,823 and 11,871 cycles. The most frequent clinical outcomes were medical/surgical remission (medication-free) and mild disease (on 5-aminosalicylates, antibiotics, topical corticosteroids), comprising 28% and 62% of UC cycles and 24% and 51% of CD cycles respectively. The probability of drug-response in patients receiving systemic corticosteroids/immunomodulators was 0.74 in UC, 0.66 in CD. Both diseases had similar likelihood of persistent drug-dependency or drug-refractoriness. Surgery was more probable in CD, 0.20, than UC, 0.08. In terms of economic outcomes, surgery was costlier in UC per cycle, but the outlay over 10 years was greater in CD. Drug-refractory UC and CD cases engendered high costs in the cohort. Most patients on 5-aminosalicylates, corticosteroids and immunomodulators had favourable clinical and economic outcomes over 10 years. Drug-refractory and surgical patients exhibited greater long-term expenses.

CD8+CD28+ T cells might mediate injury of cardiomyocytes in acute myocardial infarction.

PubMed

Zhang, Lili; Wang, Zhiyan; Wang, Di; Zhu, Jumo; Wang, Yi

2018-06-07

CD8 + T cells accumulate in the necrotic myocardium of acute myocardial infarction (AMI). It is unclear whether CD8 + CD28 + T cells, a specific subset of CD8 + T cells, contribute to myocardial injury. In this study, 92 consecutive patients with AMI and 28 healthy control subjects were enrolled. The frequency of CD8 + CD28 + T cells in peripheral blood samples was assayed by flow cytometry. Plasma cardiac troponin I (TNI) and left ventricular ejection fraction (LVEF) were determined. Long-term prognosis of the patients was evaluated by major adverse cardiac and cerebrovascular events (MACCE) over a 12-month follow-up period. Our findings indicated that patients with AMI who presented with high numbers of CD8 + CD28 + T cells had an increased infarction size and aggravated ventricular function. We proposed that cytotoxic CD8 + CD28 + T cell-mediated myocardial necrosis may act as a novel and alternative pathway of AMI. Copyright © 2018 Elsevier Ltd. All rights reserved.

In vitro production of human antigen presenting cells issued from bone marrow of patients with cancer.

PubMed

Coulon, V; Ravaud, A; Huet, S; Gualde, N

1997-10-01

In the prospect of producing autologous antigen presenting cells (APC) to actively immunize patients with cancer against their own tumor we were interested in the in vitro generation of MC and/or dendritic cells. We observed that the best yielding in CD14+ cells was obtained by adding SCF and GM-CSF into RPMI 1640 completed medium and by using Teflon bags as culture-containers. The others growth factors tested (LIF, IL3 and M-CSF) were useless in term of production of macrophages. After a month of culture we usually obtained an average of 80% of CD14, CD33, CD64, CD11a, CD11b, CD11c and HLA-DR positive cells expressing the MGG staining phenotype of MC. For DC the best association of growth factors combined GM-CSF, IL-4 and SCF. Hence we could obtained at least 60% of CD1a+, CD14-, CD54+, CD58+, CD80+ and HLA DR+ dendritic cells.

Role of the CD34+ 38- cells in posttransplant hematopoietic recovery.

PubMed

Hénon, P; Sovalat, H; Bourderont, D; Ojeda-Uribe, M; Arkam, Y; Wunder, E; Raidot, J P; Husseini, F; Audhuy, B

1998-01-01

Using three different statistical tests in parallel, we showed in a preliminary study that neither mononuclear cells, CD34+ 33+ or 33- cells, nor CD34+ 38+ cells significantly correlated with engraftment kinetics following autologous blood cell transplantation (ABCT). We additionally demonstrated here, in a series of patients suffering from malignant diseases, that the graft content in CD34+ 38- cells is individually a more sensitive indicator of the earliest, as well as the latest post-ABCT trilineage hematopoietic recovery than the colony-forming units-granulocyte-macrophage and even the total CD34+ cell content. This suggests that the CD34+ 38- cell population is itself subdivided into two more subsets, one being already lineage-committed and responsible for short-term engraftment, the other containing only very primitive hematopoietic cells responsible for sustained engraftment. Strong arguments favor the probability that these subsets correspond to HLA-DR+ and DR cells, respectively. We also defined an optimal threshold value of 0.05 x 10(6) CD34+ 38- cells/kg of the patient's body weight (b.w.) above which a rapid and sustained trilineage engraftment safely occurs. In fact, infusion of lower numbers of cells seems to have a more significant impact on long-term compared to short-term neutrophil recovery and on platelet kinetics engraftment. We additionally looked for the eventual influence on engraftment time of the type of disease, and of post-ABCT administration of hematopoietic growth factors (HGF). When the type of disease appeared to have no influence on the engraftment time, posttransplant HGF administration significantly reduced the time to trilineage engraftment in patients transplanted with < 0.05 x 10(6) CD34+ 38- cells, thus justifying it in case of reinfusion of low numbers of CD34+ 38- cells. On the other hand, the administration of HGF after infusion of more than 0.05 x 10(6) CD34+ 38- cells/kg b.w. did not hasten more, or only very little, the engraftment time, thus becoming not only unprofitable for the patients but costly as well.

Metal exposure and effects in voles and small birds near a mining haul road in Cape Krusenstern National Monument, Alaska.

PubMed

Brumbaugh, William G; Mora, Miguel A; May, Thomas W; Phalen, David N

2010-11-01

Voles and small passerine birds were live-captured near the Delong Mountain Regional Transportation System (DMTS) haul road in Cape Krusenstern National Monument in northwest Alaska to assess metals exposure and sub-lethal biological effects. Similar numbers of animals were captured from a reference site in southern Cape Krusenstern National Monument for comparison. Histopathological examination of selected organs, and analysis of cadmium, lead, and zinc concentrations in liver and blood samples were performed. Voles and small birds captured from near the haul road had about 20 times greater blood and liver lead concentrations and about three times greater cadmium concentrations when compared to those from the reference site, but there were no differences in zinc tissue concentrations. One vole had moderate metastatic mineralization of kidney tissue, otherwise we observed no abnormalities in internal organs or DNA damage in the blood of any of the animals. The affected vole also had the greatest liver and blood Cd concentration, indicating that the lesion might have been caused by Cd exposure. Blood and liver lead concentrations in animals captured near the haul road were below concentrations that have been associated with adverse biological effects in other studies; however, subtle effects resulting from lead exposure, such as the suppression of the activity of certain enzymes, cannot be ruled out for some individual animals. Results from our 2006 reconnaissance-level study indicate that overall, voles and small birds obtained from near the DMTS road in Cape Krusenstern National Monument were not adversely affected by metals exposure; however, because of the small sample size and other uncertainties, continued monitoring of lead and cadmium in terrestrial habitats near the DMTS road is advised.

Metal exposure and effects in voles and small birds near a mining haul road in Cape Krusenstern National Monument, Alaska

USGS Publications Warehouse

Brumbaugh, William G.; Mora, Miguel A.; May, Thomas W.; Phalen, David N.

2010-01-01

Voles and small passerine birds were live-captured near the Delong Mountain Regional Transportation System (DMTS) haul road in Cape Krusenstern National Monument in northwest Alaska to assess metals exposure and sub-lethal biological effects. Similar numbers of animals were captured from a reference site in southern Cape Krusenstern National Monument for comparison. Histopathological examination of selected organs, and analysis of cadmium, lead, and zinc concentrations in liver and blood samples were performed. Voles and small birds captured from near the haul road had about 20 times greater blood and liver lead concentrations and about three times greater cadmium concentrations when compared to those from the reference site, but there were no differences in zinc tissue concentrations. One vole had moderate metastatic mineralization of kidney tissue, otherwise we observed no abnormalities in internal organs or DNA damage in the blood of any of the animals. The affected vole also had the greatest liver and blood Cd concentration, indicating that the lesion might have been caused by Cd exposure. Blood and liver lead concentrations in animals captured near the haul road were below concentrations that have been associated with adverse biological effects in other studies; however, subtle effects resulting from lead exposure, such as the suppression of the activity of certain enzymes, cannot be ruled out for some individual animals. Results from our 2006 reconnaissance-level study indicate that overall, voles and small birds obtained from near the DMTS road in Cape Krusenstern National Monument were not adversely affected by metals exposure; however, because of the small sample size and other uncertainties, continued monitoring of lead and cadmium in terrestrial habitats near the DMTS road is advised.

Zebrafish Transgenic Line huORFZ Is an Effective Living Bioindicator for Detecting Environmental Toxicants

PubMed Central

Chu, Chien; Li, Hong-Ping; Tsai, Huai-Jen

2014-01-01

Reliable animal models are invaluable for monitoring the extent of pollution in the aquatic environment. In this study, we demonstrated the potential of huORFZ, a novel transgenic zebrafish line that harbors a human upstream open reading frame of the chop gene fused with GFP reporter, as an animal model for monitoring environmental pollutants and stress-related cellular processes. When huORFZ embryos were kept under normal condition, no leaked GFP signal could be detected. When treated with hazardous chemicals, including heavy metals and endocrine-disrupting chemicals near their sublethal concentrations (LC50), huORFZ embryos exhibited different tissue-specific GFP expression patterns. For further analysis, copper (Cu2+), cadmium (Cd2+) and Chlorpyrifos were applied. Cu2+ triggered GFP responses in skin and muscle, whereas Cd2+ treatment triggered GFP responses in skin, olfactory epithelium and pronephric ducts. Moreover, fluorescence intensity, as exhibited by huORFZ embryos, was dose-dependent. After surviving treated embryos were returned to normal condition, survival rates, as well as TUNEL signals, returned to pretreatment levels with no significant morphological defects observed. Such results indicated the reversibility of treatment conditions used in this study, as long as embryos survived such conditions. Notably, GFP signals decreased along with recovery, suggesting that GFP signaling of huORFZ embryos likely reflected the overall physiological condition of the individual. To examine the performance of the huORFZ line under real-world conditions, we placed huORFZ embryos in different river water samples. We found that the huORFZ embryos correctly detected the presence of various kinds of pollutants. Based on these findings, we concluded that such uORFchop-based system can be integrated into a first-line water alarm system monitoring the discharge of hazardous pollutants. PMID:24594581

Downregulation of Melanoma Cell Adhesion Molecule (MCAM/CD146) Accelerates Cellular Senescence in Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells.

PubMed

Jin, Hye Jin; Kwon, Ji Hye; Kim, Miyeon; Bae, Yun Kyung; Choi, Soo Jin; Oh, Wonil; Yang, Yoon Sun; Jeon, Hong Bae

2016-04-01

Therapeutic applications of mesenchymal stem cells (MSCs) for treating various diseases have increased in recent years. To ensure that treatment is effective, an adequate MSC dosage should be determined before these cells are used for therapeutic purposes. To obtain a sufficient number of cells for therapeutic applications, MSCs must be expanded in long-term cell culture, which inevitably triggers cellular senescence. In this study, we investigated the surface markers of human umbilical cord blood-derived MSCs (hUCB-MSCs) associated with cellular senescence using fluorescence-activated cell sorting analysis and 242 cell surface-marker antibodies. Among these surface proteins, we selected the melanoma cell adhesion molecule (MCAM/CD146) for further study with the aim of validating observed expression differences and investigating the associated implications in hUCB-MSCs during cellular senescence. We observed that CD146 expression markedly decreased in hUCB-MSCs following prolonged in vitro expansion. Using preparative sorting, we found that hUCB-MSCs with high CD146 expression displayed high growth rates, multilineage differentiation, expression of stemness markers, and telomerase activity, as well as significantly lower expression of the senescence markers p16, p21, p53, and senescence-associated β-galactosidase, compared with that observed in hUCB-MSCs with low-level CD146 expression. In contrast, CD146 downregulation with small interfering RNAs enhanced the senescence phenotype. In addition, CD146 suppression in hUCB-MSCs caused downregulation of other cellular senescence regulators, including Bmi-1, Id1, and Twist1. Collectively, our results suggest that CD146 regulates cellular senescence; thus, it could be used as a therapeutic marker to identify senescent hUCB-MSCs. One of the fundamental requirements for mesenchymal stem cell (MSC)-based therapies is the expansion of MSCs during long-term culture because a sufficient number of functional cells is required. However, long-term growth inevitably induces cellular senescence, which potentially causes poor clinical outcomes by inducing growth arrest and the loss of stem cell properties. Thus, the identification of markers for evaluating the status of MSC senescence during long-term culture may enhance the success of MSC-based therapy. This study provides strong evidence that CD146 is a novel and useful marker for predicting senescence in human umbilical cord blood-derived MSCs (hUCB-MSCs), and CD146 can potentially be applied in quality-control assessments of hUCB-MSC-based therapy. ©AlphaMed Press.

MHC class I antigens and tumour-infiltrating leucocytes in laryngeal cancer: long-term follow-up.

PubMed Central

Esteban, F.; Redondo, M.; Delgado, M.; Garrido, F.; Ruiz-Cabello, F.

1996-01-01

Alteration in MHC class I expression may be used by cancer cells to avoid immune destruction. Much experimental evidence supports this idea, although survival studies are very scarce. To investigate whether the presence or absence of HLA-A, -B and -C antigens in laryngeal carcinoma influences survival, a series of 60 primary laryngeal tumours treated surgically and normal tissues were evaluated in frozen sections for the expression of MHC class I antigens and tumour-infiltrating leucocytes (CD3, CD4, CD8, CD11b, CD1, CD20 and CD16), using monoclonal antibodies and the APAAP, technique. Long-term follow-up from the patients is available, ranging from 6 to 10 years. Thirteen tumours presented total HLA-ABC loss, five selective losses of HLA-A antigens and one absence of HLA-B antigens. Total losses were statistically associated with several clinical and pathological parameters, but there were no differences regarding tumour-infiltrating leucocytes. After conducting a prospective study, only T and N staging and scoring according to Glanz's malignancy classification were found to be independently related to patients' outcome. From our data, we conclude that neither complete loss of HLA class I antigens nor tumour-infiltrating leucocytes appear to influence survival in squamous cell carcinoma of the larynx. PMID:8956796

HTLV-1 Tax-mediated inhibition of FOXO3a activity is critical for the persistence of terminally differentiated CD4+ T cells.

PubMed

Olagnier, David; Sze, Alexandre; Bel Hadj, Samar; Chiang, Cindy; Steel, Courtney; Han, Xiaoying; Routy, Jean-Pierre; Lin, Rongtuan; Hiscott, John; van Grevenynghe, Julien

2014-12-01

The mechanisms involved in the persistence of activated CD4+ T lymphocytes following primary human T leukemia/lymphoma virus type 1 (HTLV-1) infection remain unclear. Here, we demonstrate that the HTLV-1 Tax oncoprotein modulates phosphorylation and transcriptional activity of the FOXO3a transcription factor, via upstream activation of the AKT pathway. De novo HTLV-1 infection of CD4+ T cells or direct lentiviral-mediated introduction of Tax led to AKT activation and AKT-dependent inactivation of FOXO3a, via phosphorylation of residues Ser253 and Thr32. Inhibition of FOXO3a signalling led to the long-term survival of a population of highly activated, terminally differentiated CD4+Tax+CD27negCCR7neg T cells that maintained the capacity to disseminate infectious HTLV-1. CD4+ T cell persistence was reversed by chemical inhibition of AKT activity, lentiviral-mediated expression of a dominant-negative form of FOXO3a or by specific small interfering RNA (siRNA)-mediated silencing of FOXO3a. Overall this study provides new mechanistic insight into the strategies used by HTLV-1 to increase long-term maintenance of Tax+CD4+ T lymphocytes during the early stages of HTLV-1 pathogenesis.

HTLV-1 Tax-Mediated Inhibition of FOXO3a Activity Is Critical for the Persistence of Terminally Differentiated CD4+ T Cells

PubMed Central

Bel Hadj, Samar; Chiang, Cindy; Steel, Courtney; Han, Xiaoying; Routy, Jean-Pierre; Lin, Rongtuan; Hiscott, John; van Grevenynghe, Julien

2014-01-01

The mechanisms involved in the persistence of activated CD4+ T lymphocytes following primary human T leukemia/lymphoma virus type 1 (HTLV-1) infection remain unclear. Here, we demonstrate that the HTLV-1 Tax oncoprotein modulates phosphorylation and transcriptional activity of the FOXO3a transcription factor, via upstream activation of the AKT pathway. De novo HTLV-1 infection of CD4+ T cells or direct lentiviral-mediated introduction of Tax led to AKT activation and AKT-dependent inactivation of FOXO3a, via phosphorylation of residues Ser253 and Thr32. Inhibition of FOXO3a signalling led to the long-term survival of a population of highly activated, terminally differentiated CD4+Tax+CD27negCCR7neg T cells that maintained the capacity to disseminate infectious HTLV-1. CD4+ T cell persistence was reversed by chemical inhibition of AKT activity, lentiviral-mediated expression of a dominant-negative form of FOXO3a or by specific small interfering RNA (siRNA)-mediated silencing of FOXO3a. Overall this study provides new mechanistic insight into the strategies used by HTLV-1 to increase long-term maintenance of Tax+CD4+ T lymphocytes during the early stages of HTLV-1 pathogenesis. PMID:25521510

Metronomic cyclophosphamide eradicates large implanted GL261 gliomas by activating antitumor Cd8+ T-cell responses and immune memory

PubMed Central

Wu, Junjie; Waxman, David J

2015-01-01

Cancer chemotherapy using cytotoxic drugs can induce immunogenic tumor cell death; however, dosing regimens and schedules that enable single-agent chemotherapy to induce adaptive immune-dependent ablation of large, established tumors with activation of long-term immune memory have not been identified. Here, we investigate this issue in a syngeneic, implanted GL261 glioma model in immune-competent mice given cyclophosphamide on a 6-day repeating metronomic schedule. Two cycles of metronomic cyclophosphamide treatment induced sustained upregulation of tumor-associated CD8+ cytotoxic T lymphocyte (CTL) cells, natural killer (NK) cells, macrophages, and other immune cells. Expression of CTL- and NK–cell-shared effectors peaked on Day 6, and then declined by Day 9 after the second cyclophosphamide injection and correlated inversely with the expression of the regulatory T cell (Treg) marker Foxp3. Sustained tumor regression leading to tumor ablation was achieved after several cyclophosphamide treatment cycles. Tumor ablation required CD8+ T cells, as shown by immunodepletion studies, and was associated with immunity to re-challenge with GL261 glioma cells, but not B16-F10 melanoma or Lewis lung carcinoma cells. Rejection of GL261 tumor re-challenge was associated with elevated CTLs in blood and increased CTL infiltration in tumors, consistent with the induction of long-term, specific CD8+ T-cell anti-GL261 tumor memory. Co-depletion of CD8+ T cells and NK cells did not inhibit tumor regression beyond CD8+ T-cell depletion alone, suggesting that the metronomic cyclophosphamide-activated NK cells function via CD8a+ T cells. Taken together, these findings provide proof-of-concept that single-agent chemotherapy delivered on an optimized metronomic schedule can eradicate large, established tumors and induce long-term immune memory. PMID:26137402

Hemoglobin and hematocrit values in the fish Oreochromis mossambicus (Peters) after short term exposure to copper and mercury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cyriac, P.J.; Antony, A.; Nambisan, P.N.K.

1989-08-01

Hematology is used as an index of health status in a number of fish species. Hematological changes have been detected following different types of stress conditions like exposure to pollutants, diseases, hypoxia, etc. Copper and mercury are two known aquatic pollutants. Though copper is an essential micro-nutrient, it is highly toxic at high concentrations. Mercury has no biological function to serve and causes serious impairment in the metabolic and physiological functions of the body. In this paper hematocrit and hemoglobin (Hb) values in the fish Oreochromis mossambicus separately exposed to two different sublethal concentrations of copper and mercury for amore » period of 168 h are reported.« less

Effect of ammonia on the gene expression levels of the freshwater cyclopoid Eucyclops serrulatus.

PubMed

Di Lorenzo, Tiziana; Melita, Marco; Cifoni, Marco; Galassi, Diana M P; Iannucci, Alessio; Biricolti, Stefano; Gori, Massimo; Baratti, Mariella

2017-04-01

Ammonia pollution is a critical issue in Europe, since more than half of the European freshwater bodies actually fail to meet EU quality standards for this chemical. In this study, the response of stress-related genes to a sublethal ammonia concentration has been investigated in the adults of the freshwater cyclopoid Eucyclops serrulatus. Two short-term exposures (12h and 24h) at 12mg/L NH 4 + have been tested. Results indicate that 12mg/L NH 4 + causes a significant increase in the expression of some proteins, namely CAT, HSP90 and HSP40, suggesting an activation of the protecting antioxidant system after both 12h and 24h. Copyright © 2017. Published by Elsevier B.V.

Soil geochemical factors regulate Cd accumulation by metal hyperaccumulating Noccaea caerulescens (J. Presl & C. Presl) F.K. Mey in field-contaminated soils.

PubMed

Rosenfeld, Carla E; Chaney, Rufus L; Martínez, Carmen E

2018-03-01

Cadmium contamination in soil is a substantial global problem, and of significant concern due to high food-chain transfer. Cadmium hyperaccumulators are of particular interest because of their ability to tolerate and take up significant amounts of heavy metal pollution from soils. One particular plant, Noccaea caerulescens (formerly, Thlaspi caerulescens), has been extensively studied in terms of its capacity to accumulate heavy metals (specifically Zn and Cd), though these studies have primarily utilized hydroponic and metal-spiked model soil systems. We studied Cd and nutrient uptake by two N. caerulescens ecotypes, Prayon (Zn-only hyperaccumulator) and Ganges (Zn- and Cd-hyperaccumulator) in four long-term field-contaminated soils. Our data suggest that individual soil properties such as total soil Cd, Zn:Cd molar ratio, or soil pH do not accurately predict Cd uptake by hyperaccumulating plants. Additionally, total Cd uptake by the hyperaccumulating Ganges ecotype was substantially less than its physiological capacity, which is likely due to Cd-containing solid phases (primarily iron oxides) and pH that play an important role in regulating and limiting Cd solubility. Increased P accumulation in the Ganges leaves, and greater plant Fe accumulation from Cd-containing soils suggests that rhizosphere alterations via proton, and potentially organic acid, secretion may also play a role in nutrient and Cd acquisition by the plant roots. The current study highlights the role that soil geochemical factors play in influencing Cd uptake by hyperaccumulating plants. While these plants may have high physiological potential to accumulate metals from contaminated soils, individual soil geochemical factors and the plant-soil interactions in that soil will dictate the actual amount of phytoextractable metal. This underlines the need for site-specific understanding of metal-containing solid phases and geochemical properties of soils before undertaking phytoextraction efforts. Copyright © 2017 Elsevier B.V. All rights reserved.

Long-term quality of life in cervical dystonia after treatment with abobotulinum toxin A: a 2-year prospective study.

PubMed

Kongsaengdao, Subsai; Maneeton, Narong; Maneeton, Benchalak

2018-01-01

The short-term quality of life (QoL) in cervical dystonia (CD) after treating with abobotulinum toxin A (Abo-BTX A) and neubotulinum toxin A (Neu-BTX A) have been studied in Thai CD patients. However; the long-term study has not been published. The aim of the present study was to determine long-term improvement of the health-related quality of life (HRQoL) after eight injections of Abo-BTX A over 2 years in CD patients. A 2-year prospective study on the QoL of CD patients, as measured by HRQoL, before and after receiving eight injections of Abo-BTX A at 3-month intervals over a 2-year treatment period was performed. The disease-specific HRQoL was assessed before and after the treatment by using the Cervical Dystonia Impact Profile-58 (CDIP-58) questionnaire. The general HRQoL was assessed by using the Medical Outcomes 36-Item Short Form Health Survey (SF-36), while depressive disorder screening was assessed by using the Center of Epidemiologic Studies-Depression (CES-D) questionnaire. The SF-36 and CES-D questionnaire were administered before treatment and every 3 months before the next injection for a 2-year period. A total of 20 CD patients were enrolled from January 2013 to December 2015. CDIP-58 showed a significant improvement after long-term injections of Abo-BTX A in all domains ( P < 0.001). However, only vitality domain of SF-36, which assessed general HRQoL, showed a significant improvement after long-term injections ( P = 0.037). There was no prevalence of depressive disorder in all patients (CES-D score <20) in this study. The Abo-BTX A injections at 3-month intervals over a 2-year period improved the CDIP-58 scores, which assess disease-specific HRQoL, as well as an increased vitality domain of general HRQoL. No patient suffered from depression in this study.

Ustekinumab therapy for Crohn's disease during pregnancy: a case report and review of the literature.

PubMed

Cortes, X; Borrás-Blasco, J; Antequera, B; Fernandez-Martinez, S; Casterá, E; Martin, S; Molés, J R

2017-04-01

The safety of continued ustekinumab (UST) therapy during pregnancy remains unclear in patients with Crohn's disease (CD). There are no meta-analysis reports of exposure to UST during pregnancy. The objective was to describe a case of a pregnant patient with CD who was successfully treated with UST maintenance therapy throughout the pregnancy and delivered a baby boy without any congenital malformations, neurological abnormalities or birth defects. A 37-year-old patient with CD treated with UST became pregnant. She had been receiving UST for 8 months at the time. After discussion with the patient and the obstetric team, the UST therapy was continued. The result of treatment was an uneventful pregnancy with delivery, at term, of a healthy boy and the maintenance of clinical, biological and endoscopic remission of CD during and after pregnancy. To our knowledge, this is the first reported use of continued UST therapy for CD throughout a pregnancy. The result of treatment was an uncomplicated pregnancy with the mother giving birth to a healthy boy at term and the maintenance of clinical biological and endoscopic remission of CD during and after pregnancy. © 2016 John Wiley & Sons Ltd.

Carbon Ion Irradiated Neural Injury Induced the Peripheral Immune Effects in Vitro or in Vivo

PubMed Central

Lei, Runhong; Zhao, Tuo; Li, Qiang; Wang, Xiao; Ma, Hong; Deng, Yulin

2015-01-01

Carbon ion radiation is a promising treatment for brain cancer; however, the immune system involved long-term systemic effects evoke a concern of complementary and alternative therapies in clinical treatment. To clarify radiotherapy caused fundamental changes in peripheral immune system, examinations were performed based on established models in vitro and in vivo. We found that brain-localized carbon ion radiation of neural cells induced complex changes in the peripheral blood, thymus, and spleen at one, two, and three months after its application. Atrophy, apoptosis, and abnormal T-cell distributions were observed in rats receiving a single high dose of radiation. Radiation downregulated the expression of proteins involved in T-cell development at the transcriptional level and increased the proportion of CD3+CD4−CD8+ T-cells in the thymus and the proportion of CD3+CD4+CD8− T-cells in the spleen. These data show that brain irradiation severely affects the peripheral immune system, even at relatively long times after irradiation. In addition, they provide valuable information that will implement the design of biological-based strategies that will aid brain cancer patients suffering from the long-term side effects of radiation. PMID:26633364

Mass-dependent cadmium isotopic variations in nature with emphasis on the marine environment

NASA Astrophysics Data System (ADS)

Schmitt, Anne-Désirée; Galer, Stephen J. G.; Abouchami, Wafa

2009-01-01

We report a survey of natural mass-dependent cadmium isotope fractionation measured by thermal ionization mass spectrometry using a double-spike technique (DS-TIMS). Over sixty samples of natural terrestrial Cd from diverse environments, including MORB, OIB, continental loess, hydrogenic and hydrothermal ferromanganese deposits, and sphalerites (both oceanic and from major continental ore deposits) were analysed. Our results are expressed in terms of ɛ 112/110Cd, which are deviations in 112Cd/ 110Cd from our in-house JMC Cd standard in parts per 10 4. The total ɛ 112/110Cd variation is relatively small, with a range of only 5 ɛ-units, and is one-to-two orders of magnitude smaller than that previously found in meteorites. The MORB, OIB and loess ɛ 112/110Cd values are similar and provide a good estimate for the bulk silicate Earth (BSE) value which is - 0.95 ± 0.12 relative to our Cd standard (ɛ 112/110Cd = + 0.16 relative to Münster JMC Cd). Taken together, these data suggest little Cd isotope fractionation takes place during crust-mantle segregation. Cd isotopic compositions of continental sphalerite (ZnS) deposits worldwide and high-temperature oceanic hydrothermal sulphides show remarkably similar ɛ 112/110Cd values, consistent with our estimate for the BSE. In contrast, mid-temperature oceanic sulphides from a single extinct hydrothermal chimney display over 4 ɛ-units variation — along with the most negative values. These variations are most probably caused by precipitation/redissolution of sulphide phases en route within the hydrothermal system. The ɛ 112/110Cd variability found in worldwide marine Fe-Mn deposits reflects the seawater Cd isotope signal upon precipitation from ambient seawater. A decrease in ɛ 112/110Cd is observed in passing from shallow-water Fe-Mn deposits to those from deeper waters (> 2000 m depth). This shift is explained by biological fractionation related to the uptake of dissolved seawater Cd by phytoplankton in the upper water column. The relatively uniform ɛ 112/110Cd values close to zero at great depths are consistent with regeneration and remineralization of Cd at depth. Our data suggest that Cd isotopes - much like the Cd/Ca ratio in foraminifera - could potentially serve as a proxy for past changes in biological productivity. The temporal Cd isotope record in a Fe-Mn crust archive at 2000 m depth from the NE Atlantic suggests no gross long-term changes in Cd cycling took place over the past 8 Ma.

Lethal and sublethal effects of seven insecticides on three beneficial insects in laboratory assays and field trials.

PubMed

Fernandes, Maria E S; Alves, Flávia M; Pereira, Renata C; Aquino, Leonardo A; Fernandes, Flávio L; Zanuncio, José C

2016-08-01

Lethal and sublethal effects of insecticides on target and non-target arthropods are a concern of pest management programs. Cycloneda sanguinea, Orius insidiosus and Chauliognathus flavipes are important biological control agents for aphids, whitefly, lepidopterus eggs, thrips and mites. All three test species were subjected to a toxicity study using the insecticides acephate, bifenthrin, chlorantraniliprole, chlorpyrifos, deltamethrin, imidacloprid, and thiamethoxam. Experiments were done in the lab and field. In the laboratory we evaluated the mortality and sublethal effects of the concentration that killed 20% of the population (LC20) on feeding, repellence and reproduction of the species tested. The lethal effects of these insecticides at the recommended doses was evaluated in the field. Concentration-response bioassays indicated chlorantraniliprole had the lowest toxicity, while chlorpyrifos and acephate were the most toxic. Test species exposed to filter paper surfaces treated with pyrethroids, neonicotinoids and organophosphates were repelled. On the other hand, test species were not repelled from surfaces treated with chlorantraniliprole. Chlorantraniliprole therefore seemed to be the least dangerous insecticide for these three beneficial arthropod test species. Copyright © 2016 Elsevier Ltd. All rights reserved.

In vitro effects of thiamethoxam on larvae of Africanized honey bee Apis mellifera (Hymenoptera: Apidae).

PubMed

Tavares, Daiana Antonia; Roat, Thaisa Cristina; Carvalho, Stephan Malfitano; Silva-Zacarin, Elaine Cristina Mathias; Malaspina, Osmar

2015-09-01

Several investigations have revealed the toxic effects that neonicotinoids can have on Apis mellifera, while few studies have evaluated the impact of these insecticides can have on the larval stage of the honeybee. From the lethal concentration (LC50) of thiamethoxam for the larvae of the Africanized honeybee, we evaluated the sublethal effects of this insecticide on morphology of the brain. After determine the LC50 (14.34 ng/μL of diet) of thiamethoxam, larvae were exposed to a sublethal concentration of thiamethoxam equivalent to 1.43 ng/μL by acute and subchronic exposure. Morphological and immunocytochemistry analysis of the brains of the exposed bees, showed condensed cells and early cell death in the optic lobes. Additional dose-related effects were observed on larval development. Our results show that the sublethal concentrations of thiamethoxam tested are toxic to Africanized honeybees larvae and can modulate the development and consequently could affect the maintenance and survival of the colony. These results represent the first assessment of the effects of thiamethoxam in Africanized honeybee larvae and should contribute to studies on honey bee colony decline. Copyright © 2015 Elsevier Ltd. All rights reserved.

Lethal and Sublethal Effects of Clothianidin on the Development and Reproduction of Bemisia tabaci (Hemiptera: Aleyrodidae) MED and MEAM1

PubMed Central

Fang, Yong; Wang, Jinda; Luo, Chen; Wang, Ran

2018-01-01

Abstract The Bemisia tabaci (Gennadius) cryptic species complex includes important crop pests, and among them, the cryptic species Mediterranean (MED) and Middle East-Asia Minor 1 (MEAM1) cause substantial crop losses in China. The second-generation neonicotinoid clothianidin acts as an agonist of the nicotinic acetylcholine receptor in the insect nervous system and has both stomach and contact activity. In this study, the toxicity of clothianidin and five other insecticides to MED and MEAM1 was examined. The sublethal effects of clothianidin on the development and reproduction of MED and MEAM1 were also investigated. Among the six insecticides tested, clothianidin showed toxicities to both MED and MEAM1 adults with LC50 values of 5.23 and 5.18 mg/liter, respectively. The sublethal effects of clothianidin were assessed by treating MED and MEAM1 adults with the LC25 of 1.58 and 1.13 mg/liter, respectively. The LC25 treatments accelerated the development of the F1 generation but reduced survival and fecundity of both species. Our results indicate that clothianidin could be useful for the management of B. tabaci MED and MEAM1. PMID:29718499

Response of Leuconostoc strains against technological stress factors: Growth performance and volatile profiles.

PubMed

Cicotello, Joaquín; Wolf, Irma V; D'Angelo, Luisa; Guglielmotti, Daniela M; Quiberoni, Andrea; Suárez, Viviana B

2018-08-01

The ability of twelve strains belonging to three Leuconostoc species (Leuconostoc mesenteroides, Leuconostoc lactis and Leuconostoc pseudomesenteroides) to grow under diverse sub-lethal technological stress conditions (cold, acidic, alkaline and osmotic) was evaluated in MRS broth. Two strains, Leuconostoc lactis Ln N6 and Leuconostoc mesenteroides Ln MB7, were selected based on their growth under sub-lethal conditions, and volatile profiles in RSM (reconstituted skim milk) at optimal and under stress conditions were analyzed. Growth rates under sub-lethal conditions were strain- and not species-dependent. Volatilomes obtained from the two strains studied were rather diverse. Particularly, Ln N6 (Ln. lactis) produced more ethanol and acetic acid than Ln MB7 (Ln. mesenteroides) and higher amounts and diversity of the rest of volatile compounds as well, at all times of incubation. For the two strains studied, most of stress conditions applied diminished the amounts of ethanol and acetic acid produced and the diversity and levels of the rest of volatile compounds. These results were consequence of the different capacity of the strains to grow under each stress condition tested. Copyright © 2018 Elsevier Ltd. All rights reserved.

Acute, sublethal, and combination effects of azadirachtin and Bacillus thuringiensis on the cotton bollworm, Helicoverpa armigera

PubMed Central

Abedi, Zahra; Saber, Moosa; Vojoudi, Samad; Mahdavi, Vahid; Parsaeyan, Ehsan

2014-01-01

Abstract The cotton bollworm, Helicoverpa armigera Hübner (Lepidoptera: Noctuidae) is a polyphagous and cosmopolitan insect pest that causes damage to various plants. In this study, the lethal and sublethal effects of azadirachtin and Bacillus thuringiensis Berliner sub sp . kurstaki (Bacillales: Bacillaceae) were evaluated on third instar H. armigera under laboratory conditions. The LC50 values of azadirachtin and Bt were 12.95 and 96.8 µg a.i./mL, respectively. A total mortality of 56.7% was caused on third instar larvae when LC20 values of the insecticides were applied in combination with each other. The LT50 values of azadirachtin and Bt were 4.8 and 3.6 days, respectively. The results of the sublethal study showed that the application of LC30 value of azadirachtin and Bt reduced the larval and pupal weight and increased larval and pupal duration of H. armigera . The longevity and fecundity of female adults were affected significantly by the insecticides. Female fecundity was reduced by the treatments, respectively. The lowest adult emergence ratio and pupation ratio were observed in the azadirachtin treatment. The results indicated that both insecticides have high potential for controlling of the pest. PMID:25373177

Gene expression in Listeria monocytogenes exposed to sublethal concentration of benzalkonium chloride.

PubMed

Tamburro, Manuela; Ripabelli, Giancarlo; Vitullo, Monia; Dallman, Timothy James; Pontello, Mirella; Amar, Corinne Francoise Laurence; Sammarco, Michela Lucia

2015-06-01

In this study, tolerance at sublethal concentration of benzalkonium chloride and transcription levels of mdrL, ladR, lde, sigB and bcrABC genes in Listeria monocytogenes strains were evaluated. Viable cells reduction occurred in 45% of strains and clinical isolates showed lower sensitivity than isolates from foods. An increased transcription of an efflux system encoding gene was found in 60% of strains, and simultaneous mdrL overexpression and ladR underexpression occurred in 30% of isolates. A significant association between reduced benzalkonium chloride activity and both mdrL and sigB overexpression was observed; sigB expression also correlated with both mdrL and ladR genes. The bcrABC gene was only found in six strains, all isolated from foods and sensitive to benzalkonium chloride, and in four strains an underexpression was observed. Disinfection at sublethal concentration was less effective in clinical isolates, and mdrL and sigB expression was significantly affected by disinfection. Further insights are needed to understand the adaptation to benzalkonium chloride and to evaluate whether changes in gene expression could affect the L. monocytogenes virulence traits and persistence in the environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goven, A.J.; Chen, S.C.; Fitzpatrick, L.C.

Lysozyme activity in earthworm (Lumbricus terrestris) coelomic fluid and coelomocytes appears sufficiently sensitive for use as a nonmammalian biomarker to detect toxic effects of sublethal body burdens of Cu[sup 2+]. Lysozyme, a phylogenetically conserved enzyme, is capable of bactericidal activity via action on peptidoglycan of gram-positive bacterial cell walls and functions as a component of an organism's innate antimicrobial defense mechanism. Coelomic fluid and coelomocyte lysozyme activities, which exhibit temperature-response patterns similar to those of human saliva, plasma, serum and leukocyte extracts, were sensitive to Cu[sup 2+] exposure. Lysozyme activity of coelomic fluid and coelomocyte extracts from earthworms exposed formore » 5 d to CuSO[sub 4], using filter paper contact exposure, decreased with increasing sublethal Cu[sup 2+] concentrations of 0.05 and 0.1 [mu]g/cm[sup 2]. Compared to controls, coelomic fluid lysozyme activity was suppressed significantly at both exposure concentrations, whereas coelomocyte extract lysozyme activity was suppressed significantly at the 0.1-[mu]g/cm[sup 2] exposure concentration. Low inherent natural variability and sensitivity to sublethal Cu[sup 2+] body burdens indicate that lysozyme activity has potential as a biomarker for assaying immunotoxicity of metals.« less

Therapeutic use of recombinant human G-CSF (RHG-CSF) in a canine model of sublethal and lethal whole-body irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Macvittie, T.J.; Monroy, R.L.; Patchen, M.L.

The short biologic half-life of the peripheral neutrophil (PMN) requires an active granulopoietic response to replenish functional PMSs and to remain a competent host defence in irradiated animals. Recombinant human G-CSF (rhG-CSF) was studied for its ability to modulate hemopoiesis in normal dogs as well as to decrease therapeutically the severity and duration of neutropenia in sublethally and lethally irradiated dogs. For the normal dog, subcutaneous administration of rhG-CSF induced neutrophilia within hours after the first injection; total PMSs continued to increase (with plateau phases) to mean peak values of 1000 per cent of baseline at the end of themore » treatment period (12-14 days). Bone-marrow-derived granulocyte-macrophage colony-forming cells (GM-CFC) increased significantly during treatment. For a sublethal 200 cGy dose, treatment with rhG-CSF for 14 consecutive days decreased the severity and shortened the duration of neutropenia and thrombocytopenia. The radiation-induced lethality of 60 per cent after a dose of 350 cGy was associated with marrow-derived GM-CFC survival of 1 per cent.« less

Survival of Escherichia coli and Salmonella spp. in estuarine environments.

PubMed Central

Rhodes, M W; Kator, H

1988-01-01

Survival of Escherichia coli and Salmonella spp. in estuarine waters was compared over a variety of seasonal temperatures during in situ exposure in diffusion chambers. Sublethal stress was measured by both selective-versus-resuscitative enumeration procedures and an electrochemical detection method. E. coli and Salmonella spp. test suspensions, prepared to minimize sublethal injury, were exposed in a shallow tidal creek and at a site 7.1 km further downriver. Bacterial die-off and sublethal stress in filtered estuarine water were inversely related to water temperature. Salmonella spp. populations exhibited significantly less die-off and stress than did E. coli at water temperatures of less than 10 degrees C. Although the most pronounced reductions (ca. 3 log units) in test bacteria occurred during seasonally warm temperatures in the presence of the autochthonous microbiota, 10(2) to 10(4) test cells per ml remained after 2 weeks of exposure to temperatures of greater than 15 degrees C. Reductions in test bacteria were associated with increases in the densities of microflagellates and plaque-forming microorganisms. These studies demonstrated the survival potential of enteric bacteria in estuarine waters and showed that survival was a function of interacting biological and physical factors. PMID:3066291

Complex physiological traits as biomarkers of the sub-lethal toxicological effects of pollutant exposure in fishes.

PubMed

McKenzie, D J; Garofalo, E; Winter, M J; Ceradini, S; Verweij, F; Day, N; Hayes, R; van der Oost, R; Butler, P J; Chipman, J K; Taylor, E W

2007-11-29

Complex physiological traits, such as routine aerobic metabolic rate or exercise performance, are indicators of the functional integrity of fish that can reveal sub-lethal toxicological effects of aquatic pollutants. These traits have proved valuable in laboratory investigations of the sub-lethal effects of heavy metals, ammonia and various xenobiotics. It is not known, however, whether they can also function as biomarkers of the complex potential range of effects upon overall functional integrity caused by exposure to mixtures of chemicals in polluted natural environments. The current study used portable swimming respirometers to compare exercise performance and respiratory metabolism of fish exposed in cages for three weeks to either clean or polluted sites on three urban European river systems: the river Lambro, Milan, Italy; the rivers Blythe, Cole and Tame, Birmingham, UK; and the river Amstel, Amsterdam, The Netherlands. The UK and Italian rivers were variously polluted with high levels of both bioavailable heavy metals and organics, and the Amstel by mixtures of bioavailable organics at high concentrations. In both the UK and Italy, indigenous chub (Leuciscus cephalus) exposed to clean or polluted sites swam equally well in an initial performance test, but the chub from polluted sites could not repeat this performance after a brief recovery interval. These animals were unable to raise the metabolic rate and allocate oxygen towards exercise in the second trial, an effect confirmed in successive campaigns in Italy. Swimming performance was therefore a biomarker indicator of pollutant exposure in chub exposed at these sites. Exposure to polluted sites on the river Amstel did not affect the repeat swimming performance of cultured cloned carp (Cyprinus carpio), indicating either a species-specific tolerance or relative absence of heavy metals. However, measurements of oxygen uptake during swimming revealed increased rates of routine aerobic metabolism in both chub and carp at polluted sites in all of the rivers studied, indicating a sub-lethal metabolic loading effect. Therefore, the physiological traits of exercise performance and metabolic rate have potential as biomarkers of the overall sub-lethal toxic effects of exposure to complex mixtures of pollutants in rivers, and may also provide insight into why fish do not colonize some polluted environments.

[Blastic plasmacytoid dendritic cell neoplasm revealed by ecchymotic lesions on the face].

PubMed

Ahogo, K-C; Wantz, M; Cliquennois, M; Gosset, P; Lebas, D; Modiano, P

2014-01-01

Cutaneous CD4+CD56+ malignant tumor proliferation was previously called "CD4/CD56 hematodermic neoplasm". However, the most recent studies have shown that the disease develops from plasmacytoid dendritic cells and the tumor has been renamed "Blastic Plasmacytoid Dendritic Cell Neoplasm" (BPDCN). It is an aggressive disease with a poor prognosis and behaves like acute leukemia in the short to moderate term. A 65-year-old man with no particular history consulted for a left laterocervical lesion of ecchymotic aspect that had appeared one year earlier. Topical corticosteroid therapy had been unsuccessful. Examination of biopsies with lymphocyte typing enabled a diagnosis of BPDCN to be made. At the histopathological level, biopsy showed an infiltrate comprising medium to large cells. Immunohistochemical examination was remarkable for the absence of expression of markers of T- and B-cell lines. However, these tumor cells expressed CD4, CD56 and TCL1. Staging of the disease was normal. Treatment with chemotherapy was initiated in collaboration with a team of hematologists. Autologous bone marrow transplant was then performed. BPDCN is a rare malignant blood dyscrasia. It is distinguished by inaugural skin involvement, with systemic manifestations occurring much later. Histopathological examination of a skin biopsy with immunostaining establishes the diagnosis. In terms of phenotype, the tumor population is highly characteristic. The cells are negative for antigens of T- and B- cell lines. However, these cells express CD4, CD56 and TCL1, which are markers of plasmacytoid dendritic cells. The disease carries a poor prognosis and evolves in the short to middle term in the same way as acute leukemia. First-line treatment consists of the chemotherapy regimens used in aggressive lymphoma or acute leukemia. A bone marrow graft is sometimes performed at the time of initial relapse. Average survival is 12 months for chemotherapy alone and 30 months for transplant after first relapse. Early bone marrow transplantation has been shown to improve survival. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Phenotypic differences in leucocyte populations among healthy preterm and full-term newborns.

PubMed

Quinello, C; Silveira-Lessa, A L; Ceccon, M E J R; Cianciarullo, M A; Carneiro-Sampaio, M; Palmeira, P

2014-07-01

The immune system of neonates has been considered functionally immature, and due to their high susceptibility to infections, the aim of this study was to analyse the phenotypic differences in leucocyte populations in healthy preterm and full-term newborns. We evaluated the absolute numbers and frequencies of dendritic cells (DCs) and DC subsets, monocytes and T and B lymphocytes and subsets in the cord blood of healthy moderate and very preterm (Group 1), late preterm (Group 2) and full-term (Group 3) newborns and in healthy adults, as controls, by flow cytometry. The analyses revealed statistically higher absolute cell numbers in neonates compared with adults due to the characteristic leucocytosis of neonates. We observed a lower frequency of CD80(+) myeloid and plasmacytoid DCs in Group 1 and reduced expression of TLR-4 on myeloid DCs in all neonates compared with adults. TLR-2(+) monocytes were reduced in Group 1 compared with Groups 2 and 3, and TLR-4(+) monocytes were reduced in Groups 1 and 2 compared with Group 3. The frequencies and numbers of naïve CD4(+) T and CD19(+) B cells were higher in the three groups of neonates compared with adults, while CD4(+) effector and effector memory T cells and CD19(+) memory B cells were elevated in adults compared with neonates, as expected. Our study provides reference values for leucocytes in cord blood from term and preterm newborns, which may facilitate the identification of immunological deficiencies in protection against extracellular pathogens. © 2014 John Wiley & Sons Ltd.

Short-term and persistent impacts on behaviors related to locomotion, anxiety, and startle responses of Japanese medaka (Oryzias latipes) induced by acute, sublethal exposure to chlorpyrifos.

PubMed

Qiu, Xuchun; Nomichi, Sayaka; Chen, Kun; Honda, Masato; Kang, Ik Joon; Shimasaki, Yohei; Oshima, Yuji

2017-11-01

Although most exposures to chlorpyrifos (CPF) in natural flowing waters are brief and episodic, there have been a few reports of the persistence of abnormal fish behaviors caused by such acute exposure. The present study focused on the behavioral and biochemical responses of Japanese medaka (Oryzias latipes) to acute, sublethal exposure to CPF, as well as the persistence of the effects during a 3-week recovery test in CPF-free water. The medaka became hyperactive and exhibited an elevated anxiety state after a 4-day exposure to 0.024mg/L of CPF, but they recovered from these abnormal behavioral responses within 7days of recovery treatment. In contrast, persistent impacts on some startle responses to a sudden stimulation (induced by a ball drop) were observed in medaka exposed to CPF. The reaction latency did not change immediately after the 4-day exposure, but was significantly prolonged by as much as 21days after the termination of exposure. The post-stimulus swimming distance within 5s significantly decreased on the day immediately after the 4-day exposure, but it significantly increased after 7days of recovery treatment. The activity of acetylcholinesterase (AChE) in the brains of medaka was significantly inhibited on the day immediately after the 4-day exposure, but it returned to 80% and 110% of that in control fish on days 7 and 21 of the recovery period, respectively. However, AChE activities in the eyes of exposed medaka were persistently inhibited and declined to 33%, 71%, and 72% of that in control fish on days 0 (immediately after the 4-day exposure), 7, and 21 of recovery, respectively. Correlation analysis suggested that the changes of AChE activities in the brains of medaka may underlie some of the observed acute behavioral changes, and the changes of AChE activities in the eyes may contribute to the persistence of the abnormalities in the reaction latency of the startle response. Our findings suggest that medaka need a long time to recover from acute, sublethal exposure to CPF, and the persistence of the behavioral abnormalities might affect their fitness in natural habitats. Copyright © 2017 Elsevier B.V. All rights reserved.

Long term cryopreservation in 5% DMSO maintains unchanged CD34(+) cells viability and allows satisfactory hematological engraftment after peripheral blood stem cell transplantation.

PubMed

Abbruzzese, L; Agostini, F; Durante, C; Toffola, R T; Rupolo, M; Rossi, F M; Lleshi, A; Zanolin, S; Michieli, M; Mazzucato, M

2013-07-01

Peripheral blood stem cell cryopreservation is associated with cell damage and decreased viability. We evaluated the impact of up to 10 years of cryopreservation (5% DMSO) on viability of CD34(+) cells utilizing graft samples of consecutive patients (2002-2012) with different malignancies who underwent stem cell collection and transplantation. Viability of CD34(+) cells from oncohaematological patients measured after 5 weeks (97·2 ± 0·6%) or after 9-10 years of cryopreservation (95·9 ± 0·5%) was unaffected. Haemoglobin, granulocyte and platelet recovery after transplantation of long-term cryopreserved grafts occurred within 8-13 days. CD34(+) stem cells can be safely stored up to 9-10 years, without affecting cell viability and clinical effectiveness. © 2013 International Society of Blood Transfusion.

Differential Requirements for T Cells in Viruslike Particle- and Rotavirus-Induced Protective Immunity▿

PubMed Central

Blutt, Sarah E.; Warfield, Kelly L.; Estes, Mary K.; Conner, Margaret E.

2008-01-01

Correlates of protection from rotavirus infection are controversial. We compared the roles of B and T lymphocytes in protective immunity induced either by intranasally administered nonreplicating viruslike particles or inactivated virus or by orally administered murine rotavirus. We found that protection induced by nonreplicating vaccines requires CD4+ T cells and CD40/CD40L. In contrast, T cells were not required for short-term protective immunity induced by infection, but both T-cell-dependent and -independent mechanisms contributed to long-term maintenance of protection. Our findings indicate that more than one marker of protective immunity exists and that these markers depend on the vaccine that is administered. PMID:18184712

Structural and {sup 31}P NMR investigation of Bi(MM'){sub 2}PO{sub 6} statistic solid solutions: Deconvolution of lattice constraints and cationic influences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Colmont, Marie; Delevoye, Laurent; Ketatni, El Mostafa

2006-07-15

Two solid solutions BiM{sub x} Mg{sub (2-x)}PO{sub 6} (with M {sup 2+}=Zn or Cd) have been studied through {sup 31}P MAS NMR. The analysis has been performed on the basis of refined crystal structures through X-ray diffraction and neutron diffraction. The BiZn {sub x} Mg{sub (2-x)}PO{sub 6} does not provide direct evidence for sensitive changes in the phosphorus local symmetry. This result is in good agreement with structural data which show nearly unchanged lattices and atomic separations through the Zn{sup 2+} for Mg{sup 2+} substitution. On the other hand, the Cd{sup 2+} for Mg{sup 2+} substitution behaves differently. Indeed, upmore » to five resonances are observed, each corresponding to one of the five first-cationic neighbour distributions, i.e. 4Mg/0Cd, 3Mg/1Cd, 2Mg/2Cd, 1Mg/3Cd and 0Mg/4Cd. Their intensities match rather well the expected weight for each configuration of the statistical Cd{sup 2+}/Mg{sup 2+} mixed occupancy. The match is further improved when one takes into account the influence of the 2nd cationic sphere that is available from high-field NMR data (18.8 T). Finally, the fine examination of the chemical shift for each resonance versus x allows to de-convolute the mean Z/a {sup 2} effective field into two sub-effects: a lattice constraint-only term and a chemical-only term whose effects are directly quantifiable. - Graphical abstract: First (CdMg){sub 4} cationic sphere influence on the {sup 31}P NMR signal in Bi(Cd,Mg){sub 2}PO{sub 6}. Display Omitted.« less

T Cell Receptor-Major Histocompatibility Complex Interaction Strength Defines Trafficking and CD103+ Memory Status of CD8 T Cells in the Brain.

PubMed

Sanecka, Anna; Yoshida, Nagisa; Kolawole, Elizabeth Motunrayo; Patel, Harshil; Evavold, Brian D; Frickel, Eva-Maria

2018-01-01

T cell receptor-major histocompatibility complex (TCR-MHC) affinities span a wide range in a polyclonal T cell response, yet it is undefined how affinity shapes long-term properties of CD8 T cells during chronic infection with persistent antigen. Here, we investigate how the affinity of the TCR-MHC interaction shapes the phenotype of memory CD8 T cells in the chronically Toxoplasma gondii- infected brain. We employed CD8 T cells from three lines of transnuclear (TN) mice that harbor in their endogenous loci different T cell receptors specific for the same Toxoplasma antigenic epitope ROP7. The three TN CD8 T cell clones span a wide range of affinities to MHCI-ROP7. These three CD8 T cell clones have a distinct and fixed hierarchy in terms of effector function in response to the antigen measured as proliferation capacity, trafficking, T cell maintenance, and memory formation. In particular, the T cell clone of lowest affinity does not home to the brain. The two higher affinity T cell clones show differences in establishing resident-like memory populations (CD103 + ) in the brain with the higher affinity clone persisting longer in the host during chronic infection. Transcriptional profiling of naïve and activated ROP7-specific CD8 T cells revealed that Klf2 encoding a transcription factor that is known to be a negative marker for T cell trafficking is upregulated in the activated lowest affinity ROP7 clone. Our data thus suggest that TCR-MHC affinity dictates memory CD8 T cell fate at the site of infection.

The brown seaweed Sargassum cymosum: changes in metabolism and cellular organization after long-term exposure to cadmium.

PubMed

Costa, Giulia B; Simioni, Carmen; Pereira, Débora T; Ramlov, Fernanda; Maraschin, Marcelo; Chow, Fungyi; Horta, Paulo A; Bouzon, Zenilda L; Schmidt, Éder C

2017-03-01

Sargassum cymosum was exposed to cadmium (Cd) to determine any physiological and ultrastructural effects. To accomplish this, S. cymosum samples were cultivated under photosynthetic active radiation (PAR) and Cd (0, 0.1, 0.2, 0.4 and 0.8 mg L -1 ) during 7 and 14 days in laboratory-controlled conditions (0 mg L -1 Cd at both exposure times as control). Seaweeds had high retention capacity (over 90 %) for both exposure times. Growth rates showed significant increases by 14 days, especially for 0.1 and 0.4 mg L -1 Cd. Photosynthetic parameters were unaffected by Cd treatments. Chlorophyll contents were present in higher concentrations for all Cd treatments compared to respective control. Carotenoid profile showed significant differences in total composition and proportion of fucoxanthin and β-carotene, and no lutein was detected at 14 days. Phenolic and flavonoid compounds showed major accumulation at 14 days. Transmission electron microscopy (TEM) analyses presented major alterations in Cd-treated samples, when compared with respective control, in particular disorganization of cell wall fibrils. When compared to respective control samples, multivariate analyses showed disparate and complex interactions among metabolites in Cd-exposed seaweeds, giving evidence of physiological defence response. Thus, it can be concluded that Cd is a stressor for S. cymosum, resulting in physiological and structural alterations related to defence mechanisms against oxidative stress and toxicological effects resulting from long-term metal exposure. However, in the present paper, some observed changes also appear to result from acclimation mechanisms under lower concentration of Cd relative to the tolerance of S. cymosum to experimental conditions.

Cyclodextrin-based metal-organic frameworks particles as efficient carriers for lansoprazole: Study of morphology and chemical composition of individual particles.

PubMed

Li, Xue; Guo, Tao; Lachmanski, Laurent; Manoli, Francesco; Menendez-Miranda, Mario; Manet, Ilse; Guo, Zhen; Wu, Li; Zhang, Jiwen; Gref, Ruxandra

2017-10-15

Cyclodextrin-based metal-organic frameworks (CD-MOFs) represent an environment-friendly and biocompatible class of MOFs drawing increasing attention in drug delivery. Lansoprazole (LPZ) is a proton-pump inhibitor used to reduce the production of acid in the stomach and recently identified as an antitubercular prodrug. Herein, LPZ loaded CD-MOFs were successfully synthesized upon the assembly with γ-CD in the presence of K + ions using an optimized co-crystallization method. They were characterized in terms of morphology, size and crystallinity, showing almost perfect cubic morphologies with monodispersed size distributions. The crystalline particles, loaded or not with LPZ, have mean diameters of around 6μm. The payloads reached 23.2±2.1% (wt) which corresponds to a molar ratio of 1:1 between LPZ and γ-CD. It was demonstrated that even after two years storage, the incorporated drug inside the CD-MOFs maintained its spectroscopic characteristics. Molecular modelling provided a deeper insight into the interaction between the LPZ and CD-MOFs. Raman spectra of individual particles were recorded, confirming the formation of inclusion complexes within the tridimensional CD-MOF structures. Of note, it was found that each individual particle had the same chemical composition. The LPZ-loaded particles had remarkable homogeneity in terms of both drug loading and size. These results pave the way towards the use of CD-MOFs for drug delivery purposes. Copyright © 2017 Elsevier B.V. All rights reserved.

Impact of deformed extreme-ultraviolet pellicle in terms of CD uniformity

NASA Astrophysics Data System (ADS)

Kim, In-Seon; Yeung, Michael; Barouch, Eytan; Oh, Hye-Keun

2015-07-01

The usage of the extreme ultraviolet (EUV) pellicle is regarded as the solution for defect control since it can protect the mask from airborne debris. However some obstacles disrupt real-application of the pellicle such as structural weakness, thermal damage and so on. For these reasons, flawless fabrication of the pellicle is impossible. In this paper, we discuss the influence of deformed pellicle in terms of non-uniform intensity distribution and critical dimension (CD) uniformity. It was found that non-uniform intensity distribution is proportional to local tilt angle of pellicle and CD variation was linearly proportional to transmission difference. When we consider the 16 nm line and space pattern with dipole illumination (σc=0.8, σr=0.1, NA=0.33), the transmission difference (max-min) of 0.7 % causes 0.1 nm CD uniformity. Influence of gravity caused deflection to the aerial image is small enough to ignore. CD uniformity is less than 0.1 nm even for the current gap of 2 mm between mask and pellicle. However, heat caused EUV pellicle wrinkle might cause serious image distortion because a wrinkle of EUV pellicle causes a transmission loss variation as well as CD non-uniformity. In conclusion, local angle of a wrinkle, not a period or an amplitude of a wrinkle is a main factor to CD uniformity, and local angle of less than ~270 mrad is needed to achieve 0.1 nm CD uniformity with 16 nm L/S pattern.

Accumulation of Multipotent Progenitor Cells on Polymethylpentene Membranes During Extracorporeal Membrane Oxygenation.

PubMed

Lehle, Karla; Friedl, Lucas; Wilm, Julius; Philipp, Alois; Müller, Thomas; Lubnow, Matthias; Schmid, Christof

2016-06-01

Multipotent progenitor cells were mobilized during pediatric extracorporeal membrane oxygenation (ECMO). We hypothesize that these cells also adhered onto polymethylpentene (PMP) fibers within the membrane oxygenator (MO) during adult ECMO support. Mononuclear cells were removed from the surface of explanted PMP-MOs (n = 16). Endothelial-like outgrowth and mesenchymal-like cells were characterized by flow cytometric analysis using different surface markers. Spindle-shaped attaching cells were identified early, but without proliferative activity. After long-term cultivation palisading type or cobblestone-type outgrowth cells with high proliferative activity appeared and were characterized as (i) leukocytoid CD45+/CD31+ (CD133+/VEGFR-II+/CD90+/CD14+/CD146dim/CD105dim); (ii) endothelial-like CD45-/CD31+ (VEGF-RII+/CD146+/CD105+/CD133-/CD14-/CD90-); and (iii) mesenchymal-like cells CD45-/CD31- (CD105+/CD90+/CD133dim/VEGFR-II-/CD146-/CD14-). The distribution of the cell populations depended on the MO and cultivation time. Endothelial-like cells formed capillary-like structures and did uptake Dil-acetylated low-density lipoprotein. Endothelial- and mesenchymal-like cells adhered on the surface of PMP-MOs. Further research is needed to identify the clinical relevance of these cells. Copyright © 2015 The Authors. Artificial Organs published by Wiley Periodicals, Inc. on behalf of International Center for Artificial Organs and Transplantation (ICAOT).

Redefining Myeloid Cell Subsets in Murine Spleen

PubMed Central

Hey, Ying-Ying; Tan, Jonathan K. H.; O’Neill, Helen C.

2016-01-01

Spleen is known to contain multiple dendritic and myeloid cell subsets, distinguishable on the basis of phenotype, function and anatomical location. As a result of recent intensive flow cytometric analyses, splenic dendritic cell (DC) subsets are now better characterized than other myeloid subsets. In order to identify and fully characterize a novel splenic subset termed “L-DC” in relation to other myeloid cells, it was necessary to investigate myeloid subsets in more detail. In terms of cell surface phenotype, L-DC were initially characterized as a CD11bhiCD11cloMHCII−Ly6C−Ly6G− subset in murine spleen. Their expression of CD43, lack of MHCII, and a low level of CD11c was shown to best differentiate L-DC by phenotype from conventional DC subsets. A complete analysis of all subsets in spleen led to the classification of CD11bhiCD11cloMHCII−Ly6CloLy6G− cells as monocytes expressing CX3CR1, CD43 and CD115. Siglec-F expression was used to identify a specific eosinophil population, distinguishable from both Ly6Clo and Ly6Chi monocytes, and other DC subsets. L-DC were characterized as a clear subset of CD11bhiCD11cloMHCII−Ly6C−Ly6G− cells, which are CD43+, Siglec-F− and CD115−. Changes in the prevalence of L-DC compared to other subsets in spleens of mutant mice confirmed the phenotypic distinction between L-DC, cDC and monocyte subsets. L-DC development in vivo was shown to occur independently of the BATF3 transcription factor that regulates cDC development, and also independently of the FLT3L and GM-CSF growth factors which drive cDC and monocyte development, so distinguishing L-DC from these commonly defined cell types. PMID:26793192

Immunosuppression With CD40 Costimulatory Blockade Plus Rapamycin for Simultaneous Islet-Kidney Transplantation in Nonhuman Primates.

PubMed

Oura, T; Hotta, K; Lei, J; Markmann, J; Rosales, I; Dehnadi, A; Kawai, K; Ndishabandi, D; Smith, R-N; Cosimi, A B; Kawai, T

2017-03-01

The lack of a reliable immunosuppressive regimen that effectively suppresses both renal and islet allograft rejection without islet toxicity hampers a wider clinical application of simultaneous islet-kidney transplantation (SIK). Seven MHC-mismatched SIKs were performed in diabetic cynomolgus monkeys. Two recipients received rabbit antithymocyte globulin (ATG) induction followed by daily tacrolimus and rapamycin (ATG/Tac/Rapa), and five recipients were treated with anti-CD40 monoclonal antibody (mAb) and rapamycin (aCD40/Rapa). Anti-inflammatory therapy, including anti-interleukin-6 receptor mAb and anti-tumor necrosis factor-α mAb, was given in both groups. The ATG/Tac/Rapa recipients failed to achieve long-term islet allograft survival (19 and 26 days) due to poor islet engraftment and cytomegalovirus pneumonia. In contrast, the aCD40/Rapa regimen provided long-term islet and kidney allograft survival (90, 94, >120, >120, and >120 days), with only one recipient developing evidence of allograft rejection. The aCD40/Rapa regimen was also tested in four kidney-alone transplant recipients. All four recipients achieved long-term renal allograft survival (100% at day 120), which was superior to renal allograft survival (62.9% at day 120) with triple immunosuppressive regimen (tacrolimus, mycophenolate mofetil, and steroids). The combination of anti-CD40 mAb and rapamycin is an effective and nontoxic immunosuppressive regimen that uses only clinically available agents for kidney and islet recipients. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Increased prevalence of psychopathology and maladaptive personality traits after long-term cure of Cushing's disease.

PubMed

Tiemensma, Jitske; Biermasz, Nienke R; Middelkoop, Huub A M; van der Mast, Roos C; Romijn, Johannes A; Pereira, Alberto M

2010-10-01

Psychopathology and maladaptive personality traits are often observed during the active phase of Cushing's disease (CD). We hypothesized that patients with long-term cure of CD show persistent psychopathology and maladaptive personality traits. Four questionnaires on frequently occurring psychopathology in somatic illnesses were used, including the Apathy Scale, Irritability Scale, Hospital Anxiety and Depression Scale, and Mood and Anxiety Symptoms Questionnaire short-form. Personality was assessed using the Dimensional Assessment of Personality Pathology short-form (DAPPs). We included 51 patients cured of CD (16% men, 53 ± 13 yr) and 51 matched controls. In addition, we included 55 patients treated for nonfunctioning pituitary macroadenomas (55% men, 62 ± 10 yr), and 55 matched controls. Mean duration of remission was 11 yr (range 1-32 yr). Compared with matched controls, patients cured from CD scored significantly worse on virtually all questionnaires. Compared with nonfunctioning pituitary macroadenoma patients, patients treated for CD scored worse on apathy (P < 0.001), irritability (P < 0.001), anxiety (P < 0.001), negative affect and lack of positive affect (P < 0.001 on both scales), somatic arousal (P < 0.001), and 11 of 18 subscales of the Dimensional Assessment of Personality Pathology short-form (P < 0.05). Patients with long-term cured CD show an increased prevalence of psychopathology and maladaptive personality traits. These observations suggest irreversible effects of previous glucocorticoid excess on the central nervous system rather than an effect of pituitary tumors and/or their treatment in general. This may also be of relevance for patients treated with high doses of exogenous glucocorticoids.

Inhibition effect of glyphosate on the acute and subacute toxicity of cadmium to earthworm Eisenia fetida.

PubMed

Zhou, Chui-Fan; Wang, Yu-Jun; Sun, Rui-Juan; Liu, Cun; Fan, Guang-Ping; Qin, Wen-Xiu; Li, Cheng-Cheng; Zhou, Dong-Mei

2014-10-01

The acute and subacute toxicities of cadmium (Cd) to earthworm Eisenia fetida in the presence and absence of glyphosate were studied. Although Cd is highly toxic to E. fetida, the presence of glyphosate markedly reduced the acute toxicity of Cd to earthworm; both the mortality rate of the earthworms and the accumulation of Cd decreased with the increase of the glyphosate/Cd molar ratio. The subcellular distribution of Cd in E. fetida tissues showed that internal Cd was dominant in the intact cells fraction and the heat-stable proteins fraction. The presence of glyphosate reduced the concentration of Cd in all fractions, especially the intact cells. During a longer period of exposure, the weight loss of earthworm and the total Cd absorption was alleviated by glyphosate. Thus, the herbicide glyphosate can reduce the toxicity and bioavailability of Cd in the soil ecosystems at both short- and long-term exposures. © 2014 SETAC.

Humoral and cellular immunity in cosmonauts after the ISS missions

NASA Astrophysics Data System (ADS)

Rykova, M. P.; Antropova, E. N.; Larina, I. M.; Morukov, B. V.

Spaceflight effects on the immune system were studied in 30 cosmonauts flown onto the International Space Station (ISS) for long- (125-195 d, n=15) and short-term (8-10 d, n=15) missions. Immunological investigations before launch and after landing were performed by using methods for quantitative and functional evaluation of the immunologically competent cells. Specific assays include: peripheral leukocyte distribution, natural killer (NK) cell cytotoxic activity, phagocytic activity of monocytes and granulocytes, proliferation of T-cells in response to a mitogen, levels of immunoglobulins IgA, IgM, IgG, virus-specific antibody and cytokine in serum. It was noticed that after long-term spaceflights the percentage of NK (CD3-/CD16+/CD56+) cells was significantly reduced compared with pre-flight data (p<0.05) and NK activity was suppressed by 20-85% as compared with pre-flight data in 12 out of 15 cosmonauts. T-lymphocyte activity was decreased by 25-39% as compared with pre-flight data in 5 out of 13 cosmonauts. However, the relative number of CD3+, CD4+ and CD8+ T-cells did not change. The functional activity of NK and T-cells decreased in some of the cosmonauts after short-term missions. On the other hand, a moderate trend upward of NK cytotoxic activity and proliferative activity of T-cells was observed in some individuals. Concentrations immunoglobulins (IgA, IgM, IgG) and levels of M and G antibodies to herpes simplex virus (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV) and herpes virus type 6 (HV6) in serum did not reveal significant changes after long- and short-term flights. Concentrations of cytokines (IL- 1β, IL-2, IL-4 and TNF- α) in serum changed in an apparently random manner as compared with values before long- and short-term missions. Despite the fact that many improvements have been made to the living conditions of aboard the ISS our investigations demonstrate the remarkable depression of the immunological function after the ISS missions. These results suggest that the clinical health risk (related to immune dysfunction) will occur during exploration class missions.

Primed tumor-reactive multifunctional CD62L+ human CD8+T-cells for immunotherapy

PubMed Central

Wölfl, Matthias; Merker, Katharina; Morbach, Henner; Van Gool, Stefaan W.; Eyrich, Matthias; Greenberg, Philip D.; Schlegel, Paul G.

2011-01-01

T-cell mediated immunotherapy against malignancies has been shown to be effective for certain types of cancer. However ex vivo expansion of tumor-reactive T-cells has been hindered by the low precursor frequency of such cells, often requiring multiple rounds of stimulation, resulting in full differentiation, loss of homing receptors and potential exhaustion of the expanded T-cells. Here we show that when using highly purified naïve CD8+ T-cells, a single stimulation with peptide pulsed, IFNγ/LPS-matured dendritic cells in combination with the sequential use of IL-21, IL-7 and IL-15 is sufficient for extensive expansion of antigen-specific T-cells. Short-term expanded T-cells were tumor-reactive, multifunctional and retained a central memory-like phenotype (CD62L+, CCR7+, CD28+). The procedure is highly reproducible and robust as demonstrated for different healthy donors and for cancer patients. Such short-term tumor-antigen-primed, multifunctional T-cells may therefore serve as a platform to target different malignancies accessible to immunotherapy. PMID:20972785

The Control of the Specificity of CD4 T Cell Responses: Thresholds, Breakpoints, and Ceilings

PubMed Central

Sant, Andrea J.; Chaves, Francisco A.; Leddon, Scott A.; Tung, Jacqueline

2013-01-01

It has been known for over 25 years that CD4 T cell responses are restricted to a finite number of peptide epitopes within pathogens or protein vaccines. These selected peptide epitopes are termed “immunodominant.” Other peptides within the antigen that can bind to host MHC molecules and recruit CD4 T cells as single peptides are termed “cryptic” because they fail to induce responses when expressed in complex proteins or when in competition with other peptides during the immune response. In the last decade, our laboratory has evaluated the mechanisms that underlie the preferential specificity of CD4 T cells and have discovered that both intracellular events within antigen presenting cells, particular selective DM editing, and intercellular regulatory pathways, involving IFN-γ, indoleamine 2,3-dioxygenase, and regulatory T cells, play a role in selecting the final peptide specificity of CD4 T cells. In this review, we summarize our findings, discuss the implications of this work on responses to pathogens and vaccines and speculate on the logic of these regulatory events. PMID:24167504

The phototoxic effects of fluoranthene on bullfrog tadpoles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walker, S.E.; Taylor, D.H.; Oris, J.T.

1995-12-31

The objective of this study was to determine the phototoxic effects of fluoranthene on bullfrog larvae by examining the relationship between median time to death and fluoranthene concentration and by examining the effects of short-term sublethal fluoranthene exposure on behavior and body condition. To determine the relationship between median time to death and fluoranthene concentration, tadpoles were exposed to either 0, 60, 80, 100 or 120 mg fluoranthene/L, and monitored for 144h under SUVR (40--50 mW/cm{sup 2} UVA, 4--6 mW/cm{sup 2} UVB). To examine the effects of fluoranthene on behavior and body condition, 20 tadpoles were exposed to either 0,more » 10, or 40 mg fluoranthene/L with simulated SUVR for either 48 or 96 h. At either 48 or 96 h ten individuals were removed and their locomotor activity was monitored and the body length and mass determined. Median time to death decreased with increased fluoranthene concentration and appears to do so in a linear fashion. Body condition was determined using a ratio index (mass/length{sup 3}) and a residual index was determined using the residuals of a regression of body length and body mass. Both exposure time and concentration affected both condition indices. Body burden was significantly affected at 10 mg fluoranthene/L. Exposure to fluoranthene for 48 h caused no significant effect on locomotor activity. However, at 96 h hyperactivity was noted in the highest fluoranthene exposure concentration. These results indicate that exposure to fluoranthene under environmentally realistic conditions can cause both lethal and sublethal effects on amphibian larvae.« less

Interactive effects of temperature and glyphosate on the behavior of blue ridge two-lined salamanders (Eurycea wilderae).

PubMed

Gandhi, Jaina S; Cecala, Kristen K

2016-09-01

The objective of the present study was to evaluate the potential interactive effects of stream temperatures and environmentally relevant glyphosate-based herbicide concentrations on movement and antipredator behaviors of larval Eurycea wilderae (Blue Ridge two-lined salamander). Larval salamanders were exposed to 1 of 4 environmentally relevant glyphosate concentrations (0.00 µg acid equivalent [a.e.]/L, 0.73 µg a.e./L, 1.46 µg a.e./L, and 2.92 µg a.e./L) at either ambient (12 °C) or elevated (23 °C) water temperature. Behaviors observed included the exploration of a novel habitat, use of refuge, habitat selection relative to a potential predator, and burst movement distance. In the absence of glyphosate, temperature consistently affected movement and refuge-use behavior, with individuals moving longer distances more frequently and using refuge less at warm temperatures; however, when glyphosate was added, the authors observed inconsistent effects of temperature that may have resulted from differential toxicity at various temperatures. Larval salamanders made shorter, more frequent movements and demonstrated reduced burst distance at higher glyphosate concentrations. The authors also found that lower glyphosate concentrations sometimes had stronger effects than higher concentrations (i.e., nonmonotonic dose responses), suggesting that standard safety tests conducted only at higher glyphosate concentrations might overlook important sublethal effects on salamander behavior. These data demonstrate that sublethal effects of glyphosate-based herbicides on natural behaviors of amphibians can occur with short-term exposure to environmentally relevant concentrations. Environ Toxicol Chem 2016;35:2297-2303. © 2016 SETAC. © 2016 SETAC.

Associations between CD24 gene polymorphisms and inflammatory bowel disease: A meta-analysis.

PubMed

Huang, Xiao-Li; Xu, Dong-Hua; Wang, Guo-Pin; Zhang, Shu; Yu, Cheng-Gong

2015-05-21

To evaluate the relationships between CD24 gene polymorphisms and the risk of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). The PubMed, Web of Science and Cochrane Library databases were searched (up to May 30, 2014). The search terms "CD24", "inflammatory bowel disease", "Crohn's disease", "Ulcerative colitis", "IBD", "CD" or "UC"; and "polymorphism", "mutation" or "variant" were used. Association studies were limited to the English language, but no limitations in terms of race, ethnicity or geographic area were employed. Stata SE12 software was used to calculate the pooled odds ratios (ORs) with 95% confidence intervals (CIs). P < 0.05 was considered statistically significant. The information was independently extracted from each eligible study by two investigators. Two common polymorphisms, C170T (rs8734) and TG1527del (rs3838646), in the CD24 gene were assessed. A total of three case-control studies including 2342 IBD patients and 1965 healthy controls were involved in this meta-analysis. The patients and controls were from Caucasian cohorts. The three articles included in this meta-analysis all conformed to Hardy-Weinberg equilibrium. This meta-analysis revealed that there were no significant associations between the two CD24 polymorphisms and the risk for IBD (all P > 0.05). However, in a disease subgroup analysis, we found that the CD24 C170T polymorphism was associated with an increased risk of UC in a dominant model (OR = 1.79, 95%CI: 1.15-2.77, P = 0.009) and an additive model (OR = 1.87, 95%CI: 1.19-2.93, P = 0.007), but this relationship was not present for CD. The CD24 TG1570del polymorphism was significantly associated with CD in the additive model (OR = 1.24, 95%CI: 1.01-1.52, P = 0.037). Our findings provide evidence that the CD24 C170T polymorphism might contribute to the susceptibility to UC, and the CD24 TG1527del polymorphism might be associated with the risk of CD.

Identification of CD34+ and CD34− leukemia-initiating cells in MLL-rearranged human acute lymphoblastic leukemia

PubMed Central

Aoki, Yuki; Watanabe, Takashi; Saito, Yoriko; Kuroki, Yoko; Hijikata, Atsushi; Takagi, Masatoshi; Tomizawa, Daisuke; Eguchi, Mariko; Eguchi-Ishimae, Minenori; Kaneko, Akiko; Ono, Rintaro; Sato, Kaori; Suzuki, Nahoko; Fujiki, Saera; Koh, Katsuyoshi; Ishii, Eiichi; Shultz, Leonard D.; Ohara, Osamu; Mizutani, Shuki

2015-01-01

Translocation of the mixed-lineage leukemia (MLL) gene with AF4, AF9, or ENL results in acute leukemia with both lymphoid and myeloid involvement. We characterized leukemia-initiating cells (LICs) in primary infant MLL-rearranged leukemia using a xenotransplantation model. In MLL-AF4 patients, CD34+CD38+CD19+ and CD34−CD19+ cells initiated leukemia, and in MLL-AF9 patients, CD34−CD19+ cells were LICs. In MLL-ENL patients, either CD34+ or CD34− cells were LICs, depending on the pattern of CD34 expression. In contrast, in patients with these MLL translocations, CD34+CD38−CD19−CD33− cells were enriched for normal hematopoietic stem cells (HSCs) with in vivo long-term multilineage hematopoietic repopulation capacity. Although LICs developed leukemic cells with clonal immunoglobulin heavy-chain (IGH) rearrangement in vivo, CD34+CD38−CD19−CD33− cells repopulated recipient bone marrow and spleen with B cells, showing broad polyclonal IGH rearrangement and recipient thymus with CD4+ single positive (SP), CD8+ SP, and CD4+CD8+ double-positive (DP) T cells. Global gene expression profiling revealed that CD9, CD32, and CD24 were over-represented in MLL-AF4, MLL-AF9, and MLL-ENL LICs compared with normal HSCs. In patient samples, these molecules were expressed in CD34+CD38+ and CD34− LICs but not in CD34+CD38−CD19−CD33− HSCs. Identification of LICs and LIC-specific molecules in primary human MLL-rearranged acute lymphoblastic leukemia may lead to improved therapeutic strategies for MLL-rearranged leukemia. PMID:25538041

Herbicide impact on the growth and reproduction of characteristic and rare arable weeds of winter cereal fields.

PubMed

Rotchés-Ribalta, Roser; Boutin, Céline; Blanco-Moreno, José M; Carpenter, David; Sans, F Xavier

2015-07-01

The decline of arable species characteristic of winter cereal fields has often been attributed to different factors related to agricultural intensification but most importantly to herbicide use. Herbicide phytotoxicity is most frequently assessed using short-term endpoints, primarily aboveground biomass. However, short-term sensitivity is usually not sufficient to detect actual effects because plants may or may not recover over time following sublethal herbicide exposures. Therefore, it is important to assess the long-term effects of herbicide applications. Annual species rely on renewable seed production to ensure their persistence; hence, assessment of herbicide sensitivity is more accurately estimated through effects on reproduction. Here we aim to assess the phytotoxicity of two commonly used herbicides: tribenuron and 2,4-D on eight plant species belonging to four families, each with one rare and one more common species. Specifically we examined the pattern of sensitivity using short-term and long-term endpoints (total aboveground biomass, total seed biomass and number of seeds) of these species; we determined the levels of and time to recovery in terms of stem length and fruit number, and assessed whether their rarity relates to their sensitivity to herbicide application. Our results suggest that although differences in herbicide sensitivity are not a direct cause of rarity for all species, it may be an important driver of declining arable plants.

Cells Isolated from Human Periapical Cysts Express Mesenchymal Stem Cell-like Properties

PubMed Central

Marrelli, Massimo; Paduano, Francesco; Tatullo, Marco

2013-01-01

We provide a detailed description of mesenchymal stem cells (MSCs) isolated from human periapical cysts, which we have termed hPCy-MSCs. These cells have a fibroblast-like shape and adhere to tissue culture plastic surfaces. hPCy-MSCs possess high proliferative potential and self-renewal capacity properties. We characterised the immunophenotype of hPCy-MSCs (CD73+, CD90+, CD105+, CD13+, CD29+, CD44+, CD45-, STRO-1+, CD146+) by flow cytometry and immunofluorescence. hPCy-MSCs possess the potential to differentiate into osteoblast- and adipocyte-like cells in vitro. Multi-potentiality was evaluated with culture-specific staining and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis for osteo/odontogenic and adipogenic markers. This is the first report to indicate that human periapical cysts contain cells with MSC-like properties. Taken together, our findings indicate that human periapical cysts could be a rich source of MSCs. PMID:24250252

Cells isolated from human periapical cysts express mesenchymal stem cell-like properties.

PubMed

Marrelli, Massimo; Paduano, Francesco; Tatullo, Marco

2013-01-01

We provide a detailed description of mesenchymal stem cells (MSCs) isolated from human periapical cysts, which we have termed hPCy-MSCs. These cells have a fibroblast-like shape and adhere to tissue culture plastic surfaces. hPCy-MSCs possess high proliferative potential and self-renewal capacity properties. We characterised the immunophenotype of hPCy-MSCs (CD73(+), CD90(+), CD105(+), CD13(+), CD29(+), CD44(+), CD45(-), STRO-1(+), CD146(+)) by flow cytometry and immunofluorescence. hPCy-MSCs possess the potential to differentiate into osteoblast- and adipocyte-like cells in vitro. Multi-potentiality was evaluated with culture-specific staining and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis for osteo/odontogenic and adipogenic markers. This is the first report to indicate that human periapical cysts contain cells with MSC-like properties. Taken together, our findings indicate that human periapical cysts could be a rich source of MSCs.

Follow-up on long-term antiretroviral therapy for cats infected with feline immunodeficiency virus.

PubMed

Medeiros, Sheila de Oliveira; Abreu, Celina Monteiro; Delvecchio, Rodrigo; Ribeiro, Anísia Praxedes; Vasconcelos, Zilton; Brindeiro, Rodrigo de Moraes; Tanuri, Amilcar

2016-04-01

Feline immunodeficiency virus (FIV) is a lentivirus that induces AIDS-like disease in cats. Some of the antiretroviral drugs available to treat patients with HIV type 1 are used to treat FIV-infected cats; however, antiretroviral therapy (ART) is not used in cats as a long-term treatment. In this study, the effects of long-term ART were evaluated in domestic cats treated initially with the nucleoside transcriptase reverse inhibitor (NTRI) zidovudine (AZT) over a period ranging from 5-6 years, followed by a regimen of the NTRI lamivudine (3TC) plus AZT over 3 years. Viral load, sequencing of pol (reverse transcriptase [RT]) region and CD4:CD8 lymphocyte ratio were evaluated during and after treatment. Untreated cats were evaluated as a control group. CD4:CD8 ratios were lower, and uncharacterized resistance mutations were found in the RT region in the group of treated cats. A slight increase in viral load was observed in some cats after discontinuing treatment. The data strongly suggest that treated cats were resistant to therapy, and uncharacterized resistance mutations in the RT gene of FIV were selected for by AZT. Few studies have been conducted to evaluate the effect of long-term antiretroviral therapy in cats. To date, resistance mutations have not been described in vivo. © ISFM and AAFP 2015.

[Morpho-functional reaction of spleen natural killer cells and macrophages to melatonin administration to the animals kept on different illumination regimens].

PubMed

Shatskikh, O A; Luzikova, E M

2012-01-01

The aim this investigation was to study the changes in the numbers of spleen CD57+ and CD68+ cells (natural killer cells and macrophages respectively) after melatonin administration to the animals kept on different illumination regimens. The experimental animals were given melatonin in dose of 0.03 mg per day for 2 and 4 weeks under conditions of natural illumination or artificial darkening. Spleen paraffin sections were stained using immunohistochemical methods for detection of CD57+ and CD68+ cells. It was shown that long-term administration of melatonin under conditions of natural illumination had an immunosuppressive effect, that was manifested by the depopulation of the marginal zones, white pulp and all the zones of the red pulp, parenchyma loosening and denudation of the reticular stroma of the organ. However, long-term hormone administration under conditions of artificial darkening had an immunostimulatory effect as evidenced by the increased inflow of immunocompetent cells into the spleen, their migration from the white pulp into the marginal zones and emigration into peripheral blood flow, concomitant with the increase in the number of lymphoid nodules. The number of CD57+ and CD68+ cells was increased in splenic periarterial lymphoid sheaths and decreased in B-dependent zones of the organ.

Does oral exposure to cadmium and lead mediate susceptibility to colitis? The dark-and-bright sides of heavy metals in gut ecology

NASA Astrophysics Data System (ADS)

Breton, Jérôme; Daniel, Catherine; Vignal, Cécile; Body-Malapel, Mathilde; Garat, Anne; Plé, Coline; Foligné, Benoît

2016-01-01

Although the heavy metals cadmium (Cd) and lead (Pb) are known environmental health concerns, their long-term impacts on gut ecology and susceptibility to gastrointestinal autoimmune diseases have not been extensively investigated. We sought to determine whether subchronic oral exposure to Cd or Pb is a risk factor for the development and progression of inflammatory bowel disease (IBD). Mice were exposed to various doses of CdCl2 or PbCl2 in drinking water for 1, 4 or 6 weeks prior to infection with Salmonella, the induction of colitis with dextran sodium sulfate (DSS) or trinitrobenzene sulfonic acid (TNBS). In human cell-based models, exposure to Cd and Pb is associated with reduced transepithelial electric resistance and changes in bacteria-induced cytokine responses. Although 1- and 6-week exposures did not have clear effects on the response to Salmonella infectious challenges, 1-week short-term treatments with CdCl2 tended to enhance intestinal inflammation in mice. Unexpectedly, subchronic exposure to Cd and (to a lesser extent) Pb significantly mitigated some of the symptoms of DSS-induced colitis and reduced the severity of TNBS colitis in a dose-dependent manner. The possible adaptive and immunosuppressive mechanisms by which heavy metals might reduce intestinal inflammation are explored and discussed.

Significant IFNγ responses of CD8+ T cells in CMV-seropositive individuals with autoimmune arthritis.

PubMed

Almanzar, Giovanni; Schmalzing, Marc; Trippen, Raimund; Höfner, Kerstin; Weißbrich, Benedikt; Geissinger, Eva; Meyer, Thomas; Liese, Johannes; Tony, Hans-Peter; Prelog, Martina

2016-04-01

Latent Cytomegalovirus (CMV) infection accelerates immunosenescence in elderly with reactivations reported in Rheumatoid Arthritis (RA) and abnormal responses towards CMV in Juvenile Idiopathic Arthritis (JIA). Considering the signs of premature T-cell immunosenescence in arthritis patients, the known effect of CMV latency on speeding up many of these signs in an age-dependent manner and the role of CMV on IFNγ-mediated inflammation in healthy elderly and RA, we hypothesized that latent CMV infection accelerates TCR repertoire restriction, loss of CD28, peripheral T-cell proliferation and aberrant IFNγ responses in arthritis patients. Unspecific and CMVpp65-specific IFNγ responses were investigated in peripheral CD8+ T-cells in RA or JIA patients and healthy, age-matched controls. Despite higher prevalence and concentrations of IgG-anti-CMV, arthritis patients showed lower unspecific IFNγ production, lower CD69-mediated activation and lower CD8+ T-cell proliferation. CMV-seropositive RA patients showed higher intracellular IFNγ production and increased proportions of CD28-CD8+ T-cells after specific CMVpp65 long-term stimulation which was not altered by in vitro blockade of TNFα or IL-6. A skewed TCR repertoire towards oligoclonality and less polyclonality was found in JIA. CMVpp65-specific IFNγ production with expansion of CD28-CD8+ T-cells suggests an efficient control of latent CMV regardless of immunosuppressive therapy or in vitro blockade of TNFα or IL-6 in CMV-seropositive arthritis patients. Increased IgG-anti-CMV antibody concentrations and increased proportions of intracellular IFNγ-producing CMVpp65-specific CD8+ T-cells in long-term cultures propose a possibly role of endogenous CMV reactivations boosting antibody levels and a higher possibly CMV-driven IFNγ-mediated inflammatory potential of CD8+ T-cells in arthritis patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Functional Mimetics of the HIV-1 CCR5 Co-Receptor Displayed on the Surface of Magnetic Liposomes.

PubMed

Kuzmina, Alona; Vaknin, Karin; Gdalevsky, Garik; Vyazmensky, Maria; Marks, Robert S; Taube, Ran; Engel, Stanislav

2015-01-01

Chemokine G protein coupled receptors, principally CCR5 or CXCR4, function as co-receptors for HIV-1 entry into CD4+ T cells. Initial binding of the viral envelope glycoprotein (Env) gp120 subunit to the host CD4 receptor induces a cascade of structural conformational changes that lead to the formation of a high-affinity co-receptor-binding site on gp120. Interaction between gp120 and the co-receptor leads to the exposure of epitopes on the viral gp41 that mediates fusion between viral and cell membranes. Soluble CD4 (sCD4) mimetics can act as an activation-based inhibitor of HIV-1 entry in vitro, as it induces similar structural changes in gp120, leading to increased virus infectivity in the short term but to virus Env inactivation in the long term. Despite promising clinical implications, sCD4 displays low efficiency in vivo, and in multiple HIV strains, it does not inhibit viral infection. This has been attributed to the slow kinetics of the sCD4-induced HIV Env inactivation and to the failure to obtain sufficient sCD4 mimetic levels in the serum. Here we present uniquely structured CCR5 co-receptor mimetics. We hypothesized that such mimetics will enhance sCD4-induced HIV Env inactivation and inhibition of HIV entry. Co-receptor mimetics were derived from CCR5 gp120-binding epitopes and functionalized with a palmitoyl group, which mediated their display on the surface of lipid-coated magnetic beads. CCR5-peptidoliposome mimetics bound to soluble gp120 and inhibited HIV-1 infectivity in a sCD4-dependent manner. We concluded that CCR5-peptidoliposomes increase the efficiency of sCD4 to inhibit HIV infection by acting as bait for sCD4-primed virus, catalyzing the premature discharge of its fusion potential.