Host Survival Rates Research Articles

The modulation of intestinal commensal bacteria possibly contributes to the growth and immunity promotion in Epinephelus akaara after feeding the antimicrobial peptide Scy-hepc.

Our previous study revealed that feeding the antimicrobial peptide (AMP) product Scy-hepc significantly enhances the growth of mariculture fish through the activation of the GH-Jak2-STAT5-IGF1 axis. However, the contribution of gut microbiota to this growth enhancement remains unclear. This study aimed to elucidate the potential mechanism involved in intestinal absorption and modulation of gut microbiota in Epinephelus akaara following Scy-hepc feeding. The results showed that a 35day regimen of Scy-hpec markedly promoted the growth of E. akaara compared to groups supplemented with either florfenicol, B. subtilis, or a vector. The growth enhancement is likely attributed to alterations in microbiota colonization in the foregut and midgut, characterized by an increasing abundance of potential probiotics (Rhizobiaceae and Lysobacter) and a decreased abundance of opportunistic pathogens (Psychrobacter and Brevundimonas) as determined by 16S rRNA analysis. Additionally, similar to the effect of florfenicol feeding, Scy-hepc significantly improved host survival rate by over 20% in response to a lethal dose challenge with Edwardsiella tarda. Further investigations demonstrated that Scy-hepc is absorbed by the fish foregut (20-40min) and midgut (20-30min) as confirmed by Western blot, ELISA, and Immunofluorescence. The absorption of Scy-hepc affected the swimming, swarming and surfing motility of Vibrio harveyi and Bacillus thuringiensis isolated from E. akaara's gut. Moreover, Scy-hepc induced the downregulation of 40 assembly genes and the upregulation expression of 5, with the most significant divergence in gene expression between opportunistic pathogens and probiotics concentrated in their motility genes (PomA/B, MotA/B). In summary, this study shows that feeding AMP Scy-hepc can promote growth and bolster immunity in E. akaara. These beneficial effects are likely due to the absorption of Scy-hepc in the fish's foregut and midgut, which modulates the colonization and motility of commensal bacteria, leading to favorable changes in the composition of the foregut and midgut microbiota. Therefore, a profound understanding of the mechanisms by which antimicrobial peptides affect host gut microbiota will contribute to a comprehensive assessment of their advantages and potential application prospects as substitutes for antibiotics in fish health and improving aquaculture practices.

Overexpression of chitinase PbChia1 from Plasmodiophora brassicae improves broad-spectrum disease resistance of Arabidopsis

ABSTRACT Chitinase plays an important role in plant resistance against chitin-containing pathogens through hydrolysis of chitin. Clubroot caused by Plasmodiophora brassicae is a major disease for cruciferous crops and vegetables worldwide. The cell wall of P. brassicae resting spores contains chitin. Chitinase is regarded as capable of improving plant resistance to fungal diseases. However, there has been no report about the function of chitinase in P. brassicae. Here, wheat germ agglutinin staining and commercial chitinase treatment demonstrated that chitin is a functional component in P. brassicae. In addition, Chitinase PbChia1 was identified by chitin pull-down assay combined with LC-MS/MS. PbChia1 was found to be a typical secreted chitinase, which could bind chitin with chitinase activity in vitro. PbChia1 could significantly decrease the resting spores of P. brassicae and therefore relieve the severity of clubroot symptom, with a biocontrol effect of 61.29%. Overexpression of PbChia1 in Arabidopsis thaliana improved its resistance to P. brassicae, increased host survival rate and seed yield, enhanced PAMPs-triggered reactive oxygen species burst, MAPK activation and expression of immune-related genes. PbChia1 transgenic plants also showed resistance to other pathogens, such as biotrophic bacterium Pst DC3000, necrotrophic fungi Sclerotinia sclerotiorum and Rhizoctonia solani. These findings indicate that chitinase PbChia1 is a candidate gene that can confer broad-spectrum disease resistance in breeding.

C1q Confers Protection Against Cryptococcal Lung Infection by Alleviating Inflammation and Reducing Cryptococcal Virulence.

To define the role of C1qa in host defense against Cryptococcus neoformans lung infection, we investigated its susceptibility to cryptococcal lung infection in mice deficient in complement factor C1qa (C1qa-/- ). We established a wild-type (WT) and C1qa-deficient murine inhalation model with C. neoformans. We compared the host survival rate, inflammatory responses, and pathogenicity of C. neoformans during the infection course between WT and C1qa-/- mice. The mortality rate of C1qa-deficient mice was significantly higher than that of wild-type mice. The increased formation of Titan cells in the lungs was associated with augmented inflammation in C1qa-deficient mice. The capacity of lung homogenate supernatant from C1qa-deficient mice to induce Titan formation in vitro was greater compared with that of wild-type mice. The C. neoformans isolated from the lungs of infected C1qa-deficient mice was more resistant to macrophage killing in vitro and caused significantly higher mortality after administration to mice compared with that isolated from WT mice. These findings reveal a novel role of C1qa in host defense against C. neoformans infection by regulating host inflammation and pathogen virulence and provide new insight into the C1q-mediated lung environment underlying the transition from yeast to Titan cell.

Effect of Ascosphaera apis Infestation on the Activities of Four Antioxidant Enzymes in Asian Honey Bee Larval Guts.

Ascosphaera apis infects exclusively bee larvae and causes chalkbrood, a lethal fungal disease that results in a sharp reduction in adult bees and colony productivity. However, little is known about the effect of A. apis infestation on the activities of antioxidant enzymes in bee larvae. Here, A. apis spores were purified and used to inoculate Asian honey bee (Apis cerana) larvae, followed by the detection of the host survival rate and an evaluation of the activities of four major antioxidant enzymes. At 6 days after inoculation (dpi) with A. apis spores, obvious symptoms of chalkbrood disease similar to what occurs in Apis mellifera larvae were observed. PCR identification verified the A. apis infection of A. cerana larvae. Additionally, the survival rate of larvae inoculated with A. apis was high at 1-2 dpi, which sharply decreased to 4.16% at 4 dpi and which reached 0% at 5 dpi, whereas that of uninoculated larvae was always high at 1~8 dpi, with an average survival rate of 95.37%, indicating the negative impact of A. apis infection on larval survival. As compared with those in the corresponding uninoculated groups, the superoxide dismutase (SOD) and catalase (CAT) activities in the 5- and 6-day-old larval guts in the A. apis-inoculated groups were significantly decreased (p < 0.05) and the glutathione S-transferase (GST) activity in the 4- and 5-day-old larval guts was significantly increased (p < 0.05), which suggests that the inhibition of SOD and CAT activities and the activation of GST activity in the larval guts was caused by A. apis infestation. In comparison with that in the corresponding uninoculated groups, the polyphenol oxidase (PPO) activity was significantly increased (p < 0.05) in the 5-day-old larval gut but significantly reduced (p < 0.01) in the 6-day-old larval gut, indicating that the PPO activity in the larval guts was first enhanced and then suppressed. Our findings not only unravel the response of A. cerana larvae to A. apis infestation from a biochemical perspective but also offer a valuable insight into the interaction between Asian honey bee larvae and A. apis.

A mannose-sensing AraC-type transcriptional activator regulates cell–cell aggregation of Vibrio cholerae

In addition to catalyzing coupled transport and phosphorylation of carbohydrates, the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) regulates various physiological processes in most bacteria. Therefore, the transcription of genes encoding the PTS is precisely regulated by transcriptional regulators depending on substrate availability. As the distribution of the mannose-specific PTS (PTSMan) is limited to animal-associated bacteria, it has been suggested to play an important role in host-bacteria interactions. In Vibrio cholerae, mannose is known to inhibit biofilm formation. During host infection, the transcription level of the V. cholerae gene encoding the putative PTSMan (hereafter referred to as manP) significantly increases, and mutations in this gene increase host survival rate. Herein, we show that an AraC-type transcriptional regulator (hereafter referred to as ManR) acts as a transcriptional activator of the mannose operon and is responsible for V. cholerae growth and biofilm inhibition on a mannose or fructose-supplemented medium. ManR activates mannose operon transcription by facilitating RNA polymerase binding to the promoter in response to mannose 6-phosphate and, to a lesser extent, to fructose 1-phosphate. When manP or manR is impaired, the mannose-induced inhibition of biofilm formation was reversed and intestinal colonization was significantly reduced in a Drosophila melanogaster infection model. Our results show that ManR recognizes mannose and fructose in the environment and facilitates V. cholerae survival in the host.

Modelling management strategies for chronic disease in wildlife: Predictions for the control of respiratory disease in bighorn sheep

Abstract Controlling persistent infectious disease in wildlife populations is an ongoing challenge for wildlife managers and conservationists worldwide, and chronic diseases in particular remain a pernicious problem. Here, we develop a dynamic pathogen transmission model capturing key features of Mycoplasma ovipneumoniae infection, a major cause of population declines in North American bighorn sheep Ovis canadensis. We explore the effects of model assumptions and parameter values on disease dynamics, including density‐ versus frequency‐dependent transmission, the inclusion of a carrier class versus a longer infectious period, host survival rates, disease‐induced mortality and recovery rates and the epidemic growth rate. Along the way, we estimate the basic reproductive ratio, R0, for M. ovipneumoniae in bighorn sheep to fall between approximately 1.36 and 1.74. We apply the model to compare efficacies across a suite of management actions following an epidemic, including test‐and‐remove, depopulation‐and‐reintroduction, range expansion, herd augmentation and density reduction. Our results suggest that test‐and‐remove, depopulation‐and‐reintroduction and range expansion could help persistently infected bighorn sheep herds recovery following an epidemic. By contrast, augmentation could lead to worse outcomes than those expected in the absence of management. Other management actions that improve host survival or reduce disease‐induced mortality are also likely to improve population size and persistence of chronically infected herds. Synthesis and applications. Dynamic transmission models like the one employed here offer a structured, logical approach for exploring hypotheses, planning field experiments and designing adaptive management. We find that management strategies that removed infected animals or isolated them within a structured metapopulation were most successful at facilitating herd recovery from a low‐prevalence, chronic pathogen. Ideally, models like ours should operate iteratively with field experiments to triangulate on better approaches for managing wildlife diseases.

Different Stress Tolerances of Juveniles of the Coral Acropora tenuis Associated with Clades C1 and D Symbiodinium.

Ikuko Yuyama, Takashi Nakamura, Tomihiko Higuchi, and Michio Hidaka (2016) Reef-building corals are often associated with multiple clades of symbiotic dinoflagellate Symbiodinium spp., where the relative composition of Symbiodinium can alter the phylogenetic properties (e.g., stress responsiveness, growth rate) of the host coral. The genus Symbiodinium contains nine clades, some of which behave differently in response to strong light and/or temperature stresses, for example, clade D Symbiodinium are thermally tolerant. However, previous studies are based on corals present in the field, and it is possible that the corals used in previous experiments did not contain single Symbiodinium clades. For an accurate assessment of the effects of each Symbiodinium clade on host thermal stress resistance, monoclonal cultures of clades C1 and D were inoculated into aposymbiotic juvenile polyps. Photosynthetic efficiency (maximum quantum yield: F v /F m) showed a decline at 30°C than at 25°C in both clades. Symbiodinium clade C1 showed a consistently higher rETRmax with larger fluctuations than clade D, with a lower survival rate of juveniles during thermal stress treatment. Under strong light exposure, corals containing clade C1 showed a greater decline in F v /F m (-74%), compared to decline in corals associated with clade D (-50%) after 3 hours. This is the first study to assess stress tolerances of juvenile corals in association with the monoclonal Symbiodinium clades C and D, and our results indicated greater tolerance of corals associated with clade D to strong light (500 μmol m-2 s-1). However, it is difficult to determine the impact of high-temperature stress on coral-algae symbiosis from photosynthetic activity. At high temperatures, clade C1 Symbiodinium exhibited high photosynthetic activity, but host survival rates were higher in corals associated with clade D Symbiodinium. Since clade C1 has a relatively high photosynthetic activity under high temperatures, clade C1 symbiosis at high temperatures might have a negative impact on corals compared with clade D.

A novel mechanism of host cell death by ESAT-6 like protein of Mycobacterium tuberculosis

Background: Mycobacterium tuberculosis (Mtb), causative agent of human tuberculosis (TB), manipulates the host immune responses for its survival. Several secretary proteins exported through ESX secretion system modulate the antibacterial effector functions of macrophages. Here we attempted to functionally elucidate the role of one of the previously uncharacterized ESAT-6 family protein in Mtb pathogenesis. Methods & Materials: Mtb gene is cloned and expressed in Mycobacterium smegmatis. Invasion assay is performed in HeLa cells where as survival assays were carried out in both mouse and human macrophages. Survival mechanisms were studied by quantifying free radicals formation and host survival rate. Induction of autophagic pathway is studied by the expression of LC3. Nuclear and chromosomal aberrations were studied using micronucleus assay. The level of cytokine expressions were measured using qPCR. Results: Recombinant Mycobacterium smegmatis strain expressing ESAT-6 family protein showed more invasion in human epithelial cells (HeLa) and survival in mouse macrophages (RAW264.7) and human monocyte derived macrophages (THP-1). The survival mechanistic studies revealed, infection induced host cell death and also up regulation of the level of nitric oxide, inducible nitric oxide synthase, reactive oxygen species, superoxide dismutase and catalase activities. Moreover, Mycobacterium smegmatis expressing ESAT-6 infection reduced T-cell survival, caused loss of mitochondrial membrane integrity, activated autophagy and also induced the expression of NF-κB and late endosomal markers such as Rab10, LAMP-2, Cathepsin-B and Cathepsin-Z in macrophages. An up regulation of both pro-inflammatory (TNF-α, IL-12) and anti-inflammatory (IL-10, TGF-β) cytokines was also observed after infection in macrophages. Genome stability studies showed that recombinant Mycobacterium smegmatis strain expressing ESAT-6 family protein infection led to several chromosomal abnormalities such as micronuclei formation in cytokinesis blocked cells, chromosomal malsegregation and nuclear fragmentation. Conclusion: We envision that this study offers a novel mechanism of host cell death by Mtb infection. Taken together, this study has identified a novel ESAT-6 like family protein that acts as virulence as well as an immunomodulatory factor to evade killing by host, and thus it may provide a novel drug target.

A novel serum protein signature associated with resistance to epidermal growth factor receptor tyrosine kinase inhibitors in head and neck squamous cell carcinoma

BackgroundAcquired resistance to tyrosine kinase inhibitors (TKIs) is becoming a major challenge in the treatment of many cancers. Epidermal growth factor receptor (EGFR) is overexpressed in squamous carcinomas, notably those of the head and neck (HNSCC), and can be targeted with several TKIs. We aimed to identify soluble proteins suitable for development as markers of EGFR TKI resistance in cancer patients to aid in early and minimally invasive assessment of therapeutic responses. MethodsResistant HNSCC cell lines were generated by exposure to an EGFR TKI, gefitinib, in vitro. Cell lines were characterised for their biological behaviour in vitro (using growth inhibition assays, flow cytometry, western blots, antibody arrays and/or immunoassays) and in vivo (using subcutaneous tumour xenografts). Sera from EGFR-treated and -untreated HNSCC patients were analysed by immunoassay. ResultsTwo independent sublines of CAL 27 and a PJ34 subline with acquired resistance to EGFR TKIs (gefitinib, erlotinib and afatinib) were developed. Resistant cells grew as highly aggressive xenografts leading to reduced host survival rates compared with EGFR-TKI sensitive cells. This suggested a link between resistance in vitro and poor prognosis in vivo. A significant upregulation of proteins linked to tumour angiogenesis and invasion was identified in resistant cells. This ‘resistance-associated protein signature’ (RAPS) was detected in the sera of a small cohort of HNSCC patients and was associated with reduced survival. ConclusionWe have identified a protein signature associated with EGFR-TKI resistance that may also be linked to poor prognosis and warrants further investigation as a potential clinical biomarker.

Comparison of Autotransporter and Ice Nucleation Protein as Carrier Proteins for Antibody Display on The Cell Surface of Escherichia coli

Antibody surface display technology is critical for novel antibody screening and antibody affinity maturation. Currently most frequently used display methods are phage display and yeast display. Although Escherichia coli (E. coli) is easily cultured and genetically manipulated, thus is potentially an excellent display host, the display technology based on E. coli has not been widely used. One of the problems is lack of efficient display of antibodies on the surface of E. coli. Many proteins have been tested as display carriers in outer membrane display in E. coli. Display systems based on autotransporter protein (AT) and ice nucleation protein (INP) is the most extensively studied. Another problem is unstable survival rates of E. coli when antibody is displayed. In this study, we systematically examined display level, antigen-binding affinity of displayed antibody and survival rate of E. coli using Ag43茁 (茁 domain of Antigen43, an AT protein) and INPNC (fragment of N-terminal and C-terminal of INP) as carrier proteins and T7, lac, araBAD as promoters for antibody expression. We found that the antigen-binding ability of the Ag43茁 based display was superior to that of the INPNC based system. As expected, T7, lac and araBAD promoters drove high, medium and low expressions of antibody. The host survival rate using T7 promoter was extremely low (INPNC: 0.0033% , Ag43茁: 0.02% , the host bearing araBAD promoter had the highest survival rate (INPNC: 37.80%, Ag43茁: 90.23%), and the lac based system had a survival rate of 2.04% (INPNC) and 13.27% (Ag43茁). Balancing the antigen-binding abilities, antibody expression levels and survival rates, a system using Ag43茁 as carrier protein and lac as promoter is the best choice for antibody display on E. coli.

Individual and Population-Level Impacts of an Emerging Poxvirus Disease in a Wild Population of Great Tits

Emerging infectious diseases of wildlife can have severe effects on host populations and constitute a pressing problem for biodiversity conservation. Paridae pox is an unusually severe form of avipoxvirus infection that has recently been identified as an emerging infectious disease particularly affecting an abundant songbird, the great tit (Parus major), in Great Britain. In this study, we study the invasion and establishment of Paridae pox in a long-term monitored population of wild great tits to (i) quantify the impact of this novel pathogen on host fitness and (ii) determine the potential threat it poses to population persistence. We show that Paridae pox significantly reduces the reproductive output of great tits by reducing the ability of parents to fledge young successfully and rear those young to independence. Our results also suggested that pathogen transmission from diseased parents to their offspring was possible, and that disease entails severe mortality costs for affected chicks. Application of multistate mark-recapture modelling showed that Paridae pox causes significant reductions to host survival, with particularly large effects observed for juvenile survival. Using an age-structured population model, we demonstrate that Paridae pox has the potential to reduce population growth rate, primarily through negative impacts on host survival rates. However, at currently observed prevalence, significant disease-induced population decline seems unlikely, although pox prevalence may be underestimated if capture probability of diseased individuals is low. Despite this, because pox-affected model populations exhibited lower average growth rates, this emerging infectious disease has the potential to reduce the resilience of populations to other environmental factors that reduce population size.

Evaluation of immunomodulatory and antitumor activity of all trans retinoic acid (ATRA) in solid tumor bearing mice

Natural or synthetic agents can modify the immune system and, in some cases, impart a therapeutic benefit. Cancer, a disease of uncontrolled growth and spread of abnormal cells, is a major cause of death. The Vitamin A metabolite all-trans retinoic acid (ATRA) and its other active derivatives are potent modulators of cell growth and differentiation, and because it has an influence on cancer, it can be used as a chemotherapeutic and -preventive agent. To evaluate the immunomodulatory activity of ATRA, the impact of treatment on various parameters, e.g. delayed-type hypersensitivity (DTH), bone marrow cellularity, hematology, and levels of esterase-positive cells, was assessed in Balb/c mice. To evaluate antitumor effects of ATRA, tumor volume and host survival rate were monitored in B16F10 melanoma cell-injected mice. The results showed that administration of ATRA (0.60 mg/kg/dose, IP) caused a decrease in DTH (footpad thickness) in response to challenge with sheep red blood cells (SRBC) in SRBC-sensitized hosts. ATRA also caused increases in WBC counts and bone marrow cell numbers. In tumor-inoculated mice, ATRA caused tumor growth suppression and gave rise to a heightened survival rate. It was also found that ATRA had differential effects on serum levels of reduced glutathione (GSH) and nitric oxide (NO) was reduced in serum. Based on these results, we conclude that ATRA has a potent immunomodulatory potential but also could significantly impact upon solid tumor growth and prolong host survival.

Sodium Chloride Inhibits the Growth and Infective Capacity of the Amphibian Chytrid Fungus and Increases Host Survival Rates

The amphibian chytrid fungus Batrachochytrium dendrobatidis is a recently emerged pathogen that causes the infectious disease chytridiomycosis and has been implicated as a contributing factor in the global amphibian decline. Since its discovery, research has been focused on developing various methods of mitigating the impact of chytridiomycosis on amphibian hosts but little attention has been given to the role of antifungal agents that could be added to the host's environment. Sodium chloride is a known antifungal agent used routinely in the aquaculture industry and this study investigates its potential for use as a disease management tool in amphibian conservation. The effect of 0–5 ppt NaCl on the growth, motility and survival of the chytrid fungus when grown in culture media and its effect on the growth, infection load and survivorship of infected Peron's tree frogs (Litoria peronii) in captivity, was investigated. The results reveal that these concentrations do not negatively affect the survival of the host or the pathogen. However, concentrations greater than 3 ppt significantly reduced the growth and motility of the chytrid fungus compared to 0 ppt. Concentrations of 1–4 ppt NaCl were also associated with significantly lower host infection loads while infected hosts exposed to 3 and 4 ppt NaCl were found to have significantly higher survival rates. These results support the potential for NaCl to be used as an environmentally distributed antifungal agent for the prevention of chytridiomycosis in susceptible amphibian hosts. However, further research is required to identify any negative effects of salt exposure on both target and non-target organisms prior to implementation.

Betanodavirus induces oxidative stress-mediated cell death that prevented by anti-oxidants and zfcatalase in fish cells.

The role of oxidative stress in the pathogenesis of RNA nervous necrosis virus infection is still unknown. Red-spotted grouper nervous necrosis virus (RGNNV) induced free radical species (ROS) production at 12–24 h post-infection (pi; early replication stage) in fish GF-1 cells, and then at middle replication stage (24–48 h pi), this ROS signal may upregulate some expressions of the anti-oxidant enzymes Cu/Zn SOD and catalase, and eventually expression of the transcription factor Nrf2. Furthermore, both antioxidants diphenyliodonium and N-acetylcysteine or overexpression of zebrafish catalase in GF-1 cells also reduced ROS production and protected cells for enhancing host survival rate due to RGNNV infection.Furthermore, localization of ROS production using esterase activity and Mitotracker staining assays found that the ROS generated can affect mitochondrial morphology changes and causes ΔΨ loss, both of which can be reversed by antioxidant treatment. Taken together, our data suggest that RGNNV induced oxidative stress response for playing dual role that can initiate the host oxidative stress defense system to upregulate expression of antioxidant enzymes and induces cell death via disrupting the mitochondrial morphology and inducing ΔΨ loss, which can be reversed by anti-oxidants and zfcatalase, which provide new insight into betanodavirus-induced ROS-mediated pathogenesis.

Egg dispersion is more important than competition type for herbivores attacked by a parasitoid

Herbivore fitness can be altered by a combination of interacting organisms, such as its food plant, conspecifics, and predators/parasitoids. Here, we tested relative effects of plant species, herbivore intraspecific competition type, and spatial distribution of the herbivore among plant units on herbivore survival and whether parasitoids modified these effects. We used an endophagous bruchine seed predator Callosobruchusmaculatus for the herbivore, and a braconid wasp Heterospilusprosopidis for the parasitoid. The survival rate of C. maculatus was measured for each of 16 combinations of two plants (bean species, Vigna unguiculata and V. radiata), two competition types of C. maculatus larvae (contest and scramble), two spatial distributions of hosts [sparse (1 C. maculatus larva per seed over 20 seeds) and dense (2 C. maculatus larvae per seed over ten seeds)], and with/without a parasitoid pair. In the absence of the parasitoid, C. maculatus survival rate was lower with V. radiata and in the contest type. With the parasitoid, the proportion parasitized hosts was independent of total host density. Neither the proportion of parasitized hosts nor host survival rate was affected by plant species or host strain, but they were affected by host spatial distribution. When host distribution was dense, a higher proportion of hosts were parasitized, and C. maculatus survival rate was lower. Here we discuss parasitoid potential as a selective agent for the sparse within-pod distribution of its hosts in the field.

Optimal release strategies for captive-bred animals in reintroduction programs: Experimental infections using the guppy as a model organism

Reintroduction of captive-bred individuals for supplementation or re-establishment of wild populations has become increasingly important to prevent the extinction of many endangered species. Despite the importance of reintroductions for conservation biology, few studies have empirically evaluated the potential impacts of reintroductions of naïve organisms on disease outbreaks in native wild populations. Here, we use a model organism, the guppy ( Poecilia reticulata) and its ubiquitous parasite ( Gyrodactylus turnbulli) to evaluate: (i) the most effective release procedure (i.e. en masse vs. gradual release) that minimises host mortality and parasite load, (ii) the effect of pre-exposure to the parasite on host susceptibility, and (iii) the potential advantage of removing the most susceptible individuals before release. We could not detect a statistically significant difference in host survival rates between release protocols and pre-exposure regime. However, the parasite population went extinct significantly more often when pre-exposed fish were released. Furthermore, the parasite load of individual guppies by the end of the reintroduction was significantly lower in treatments where fish had been pre-exposed to parasites than in treatments with naïve guppies. Additionally, pre-exposure of hosts provided important information about their level of resistance when reintroduced. These findings suggest that pre-exposure to native parasites could be beneficial for the survival rate of captive-bred animals when reintroduced in the wild. We discuss the practicalities of these potential release strategies.

P38 MAPK-Dependent Phagocytic Encapsulation Confers Infection Tolerance in Drosophila

Hosts employ a combination of two distinct yet compatible strategies to defend themselves against parasites: resistance, the ability to limit parasite burden, and tolerance, the ability to limit damage caused by a given parasite burden. Animals typically exhibit considerable genetic variation in resistance to a variety of pathogens; however, little is known about whether animals can evolve tolerance. Using a bacterial infection model in Drosophila, we uncovered a p38 MAP kinase-mediated mechanism of tolerance to intracellular bacterial infection as measured by the extent to which the host's survival rate increased or was maintained despite increasing bacterial burden. This increased survival was conferred primarily by a tolerance strategy whereby p38-dependent phagocytic encapsulation of bacteria resulted in enlarged phagocytes that trap bacteria. These results suggest that phagocytic responses are not restricted to resistance mechanisms but can also be applied to tolerance strategies for intracellular encapsulation of pathogens during the invertebrate immune response.

This Month in Anesthesiology

Mechanisms underlying the alleged cancer-promoting effects of blood transfusion are unknown, including the involvement of donors' leukocytes, erythrocytes, and soluble factors. Two tumor models were used in rats to study the impact of blood transfusion on the host ability to clear circulating cancer cells and host survival rates. The potential deleterious characteristics of the transfusion were also studied. Blood transfusion, in conjunction with blood storage time, was found to be an independent and significant risk factor for cancer progression, and aged erythrocytes mediated the effects. In rats, transfusion of fresh blood is less harmful than transfusion of stored blood. These results have implications for cancer patients receiving erythrocyte transfusions. See the accompanying Editorial View on page 951 This study examined the effect of isoflurane on γ-aminobutyric acid (GABA) levels in pontine reticular formation and the effect of drugs that increase or decrease GABA levels in the pontine reticular formation in experimental animals. Compared with wakefulness, GABA levels were significantly decreased by isoflurane. Nipecotic acid increased GABA levels and increased isoflurane induction time, whereas 3-mercaptopropionic acid decreased GABA levels and decreased isoflurane induction time. These results indicate that decreasing rather than increasing pontine reticular formation GABA levels is one mechanism by which isoflurane causes loss of consciousness and altered cortical excitability. See the accompanying Editorial View on page 948 Using a new risk scale developed for children, the effect size was calculated for treatments recommended for the pediatric population in the new Guidelines for the Management of Postoperative Nausea and Vomiting. Six single-drug therapies and five combination treatments were analyzed for risk reduction. With single-agent therapy using the 5-hydroxytryptamine receptor antagonists or dexamethasone, a 50–60% relative risk reduction is expected. Droperidol offers only a 40% decrease. With the combinations of a 5-hydroxytryptamine receptor antagonist and dexamethasone, a relative risk reduction in vomiting of about 80% is expected.In the senescent heart, β-adrenergic responsiveness is altered in parallel with β1- and β2-adrenoceptor down-regulation. This study tested the hypothesis that the β3-adrenoceptor plays a role in β-adrenergic receptor dysfunction in the senescent heart. β-adrenergic responses were investigated in vivo using echocardiography and in vitro using isolated left ventricular papillary muscle in young adult and senescent rats. An impaired positive inotropic effect in parallel with β3-adrenoceptor up-regulation was confirmed in senescent hearts both in vivo and in vitro . In the senescent group, the positive inotropic effect of β-adrenergic agonists was partially restored by nitric oxide synthase inhibitors. This was not the case in the young adult group. These results indicate β3-adrenoceptor overexpression plays a role in the altered β-adrenergic response in senescent cardiomyopathy via the induction of nitric oxide. See the accompanying Editorial View on page 956 Supervision of anesthesia residents by an attending anesthesiologist is associated with a decreased incidence of complications during emergent intubations outside the operating room. See the accompanying Editorial View on page 945 Training for fiberoptic orotracheal intubation using a high-fidelity simulator was not different than training with a low-fidelity simulator.Desmopressin is associated with a significant reduction in transfusion of blood products.This review evaluates different methods for determination of sympathetic nervous system activity and describes its role in human neurohumoral circulatory control. The effects of general anesthesia on sympathetic nervous system activity and their relevance for clinical anesthesia are discussed.

Blood Transfusion Promotes Cancer Progression: A Critical Role for Aged Erythrocytes

In cancer patients, allogeneic blood transfusion is associated with poorer prognosis, but the independent effect of the transfusion is controversial. Moreover, mediating mechanisms underlying the alleged cancer-promoting effects of blood transfusion are unknown, including the involvement of donors' leukocytes, erythrocytes, and soluble factors. Two syngeneic tumor models were used in Fischer 344 rats, the MADB106 mammary adenocarcinoma and the CRNK-16 leukemia. Outcomes included host ability to clear circulating cancer cells, and host survival rates. The independent impact of blood transfusion was assessed, and potential deleterious characteristics of the transfusion were studied, including blood storage duration; the role of erythrocytes, leukocyte, and soluble factors; and the kinetics of the effects. Blood transfusion was found to be an independent and significant risk factor for cancer progression in both models, causing up to a fourfold increase in lung tumor retention and doubling mortality rates. Blood storage time was the critical determinant of these deleterious effects, regardless of whether the transfused blood was allogeneic or autogenic. Surprisingly, aged erythrocytes (9 days and older), rather than leukocytes or soluble factors, mediated the effects, which occurred in both operated and nonoperated animals. The effects of erythrocytes transfusion in the MADB106 model emerged immediately and dissipated within 24 h. In rats, transfusion of fresh blood is less harmful than transfusion of stored blood in the context of progressing malignancies. Further studies should address mediating mechanisms through which erythrocytes' storage duration can impact the rate of complications while treating malignant diseases and potentially other pathologies.

The Effect of Carrier Substrate, Dose Rate and Time of Application on Biocontrol Efficacy of Fungal Antagonists Against Armillaria Root Rot of Strawberry Plants

ABSTRACT In a glasshouse experiment using potted strawberry plants (cv. Cambridge Favourite) as hosts, the effect of selected fungal antagonists grown on 25 or 50 g of mushroom compost containing autoclaved mycelia of Agaricus bisporus, or wheat bran was evaluated against Armillaria mellea. Another glasshouse experiment tested the effect of application time of the antagonists in relation to inoculations with the pathogen. A significant interaction was found between the antagonists, substrates and dose rates. All the plants treated with Chaetomium olivaceum isolate Co on 50 g wheat bran survived until the end of the experiment which lasted 482 days, while none of them survived when this antagonist was added to the roots of the plants on 25 g wheat bran or 25 or 50 g mushroom compost. Dactylium dendroides isolate SP had a similar effect, although with a lower host survival rate of 33.3%. Trichoderma hamatum isolate Tham1 and T. harzianum isolate Th23 protected 33.3% of the plants when added on 50 g and none when added on 25 g of either substrate, while 66.7% of the plants treated with T. harzianum isolate Th2 on 25 g, or T. viride isolate Tv3 on 50 g wheat bran, survived. Application of the antagonists on mushroom compost initially resulted in development of more leaves and healthier plants, but this effect was not sustained. Eventually, plants treated with the antagonists on wheat bran had significantly more leaves and higher health scores. The plants treated with isolate Th2 and inoculated with Armillaria at the same time had a survival rate of 66.7% for the duration of the experiment (475 days), while none of them survived that long when the antagonist and pathogen were applied with an interval of 85 days in either sequence. C. olivaceum isolate Co showed a protective effect only, as 66.7% of the plants survived when they were treated with the antagonist 85 days before inoculation with the pathogen, while none of them survived when the antagonist and pathogen were applied together or the infection preceded protection.