Honey bee queen health is unaffected by contact exposure to pesticides commonly found in beeswax.

Honey bee queen health is crucial for colony health and productivity, and pesticides have been previously associated with queen loss and premature supersedure. Prior research has investigated the effects of indirect pesticide exposure on queens via workers, as well as direct effects on queens during development. However, as adults, queens are in constant contact with wax as they walk on comb and lay eggs; therefore, direct pesticide contact with adult queens is a relevant but seldom investigated exposure route. Here, we conducted laboratory and field experiments to investigate the impacts of topical pesticide exposure on adult queens. We tested six pesticides commonly found in wax: coumaphos, tau-fluvalinate, atrazine, 2,4-DMPF, chlorpyriphos, chlorothalonil, and a cocktail of all six, each administered at 1, 4, 8, 16, and 32 times the concentrations typically found in wax. We found no effect of any treatment on queen mass, sperm viability, or fat body protein expression. In a field trial testing queen topical exposure of a pesticide cocktail, we found no impact on egg-laying pattern, queen mass, emergence mass of daughter workers, and no proteins in the spermathecal fluid were differentially expressed. These experiments consistently show that pesticides commonly found in wax have no direct impact on queen performance, reproduction, or quality metrics at the doses tested. We suggest that previously reported associations between high levels of pesticide residues in wax and queen failure are most likely driven by indirect effects of worker exposure (either through wax or other hive products) on queen care or queen perception.

Lampaya Medicinalis Phil. decreases lipid-induced triglyceride accumulation and proinflammatory markers in human hepatocytes and fat body of Drosophila melanogaster.

BACKGROUND: Excess hepatic triglyceride (TG) accumulation (steatosis) commonly observed in obesity, may lead to non-alcoholic fatty liver disease (NAFLD). Altered regulation of intracellular lipid droplets (LD) and TG metabolism, as well as activation of JNK-mediated proinflammatory pathways may trigger liver steatosis-related disorders. Drosophila melanogaster is an animal model used for studying obesity and its associated disorders. In Drosophila, lipids and glycogen are stored in the fat body (FB), which resembles mammalian adipose tissue and liver. Dietary oversupply leads to obesity-related disorders, which are characterized by FB dysfunction. Infusions of Lampaya medicinalis Phil. (Verbenaceae) are used in folk medicine of Chile to counteract inflammatory diseases. Hydroethanolic extract of lampaya (HEL) contains considerable amounts of flavonoids that may explain its anti-inflammatory effect. METHODS: We studied whether HEL affects palmitic acid (PA, C16:0) and oleic acid (OA; C18:1)-induced TG accumulation and proinflammatory marker content in HepG2 hepatocytes as well as impaired lipid storage and proinflammatory molecule expression in Drosophila melanogaster fed a high-fat diet (HFD). RESULTS: In HepG2 hepatocytes, exposure to OA/PA elevated TG content, FABP4, ATGL and DGAT2 expression, and the JNK proinflammatory pathway, as well as TNF-α and IL-6 production, while diminished FAS expression. These effects were prevented by HEL co-treatment. In Drosophila larvae fed a HFD, HEL prevented TG accumulation and downregulated proinflammatory JNK pathway activation. CONCLUSION: HEL effect counteracting OA/PA- and HFD-induced lipid accumulation and proinflammatory marker expression in HepG2 hepatocytes and Drosophila larvae may represent a preventive approach against hepatic steatosis and inflammation, associated to obesity and NAFLD.

Effects of short- and long-term exposure to cadmium on salivary glands and fat body of soil centipede Lithobius forficatus (Myriapoda, Chilopoda): Histology and ultrastructure.

Cadmium (Cd) is the most widely studied heavy metal in terms of food-chain accumulation and contamination because it can strongly affect all environments (e.g., soil, water, air). It can accumulate in different tissues and organs and can affect the organism at different levels of organization: from organs, tissues and cells though cell organelles and structures to activation of mechanisms of survival and cell death. In soil-dwelling organisms heavy metals gather in all tissues with accumulation properties: midgut, salivary glands, fat body. The aim of this study was to describe the effects of cadmium on the soil species Lithobius forficatus, mainly on two organs responsible for gathering different substances, the fat body and salivary glands, at the ultrastructural level. Changes caused by cadmium short- and long-term intoxication, connected with cell death (autophagy, apoptosis, necrosis), and the crosstalk between them, were analyzed. Adult specimens of L. forficatus were collected in a natural environment and divided into three experimental groups: C (the control group), Cd1 (cultured in soil with 80 mg/kg of CdCl2 for 12 days) and Cd2 (cultured in soil with 80 mg/kg of CdCl2 for 45 days). Transmission electron microscopy revealed ultrastructural alterations in both of the organs analyzed (reduction in the amount of reserve material, the appearance of vacuoles, etc.). Qualitative analysis using TUNEL assay revealed distinct crosstalk between autophagy and necrosis in the fat body adipocytes, while crosstalk between autophagy, apoptosis and necrosis in the salivary glands was detected in salivary glands of the centipedes examined here. We conclude that different organs in the body can react differently to the same stressor, as well as to the same concentration and time of exposure. Different mechanisms at the ultrastructural level activate different types of cell death and with different dynamics.

CDKI-73 is a Novel Pharmacological Inhibitor of Rab11 Cargo Delivery and Innate Immune Secretion.

Innate immunity is critical for host defence against pathogen and environmental challenge and this involves the production and secretion of immune mediators, such as antimicrobial peptides and pro-inflammatory cytokines. However, when dysregulated, innate immunity can contribute to multifactorial diseases, including inflammatory rheumatic disorders, type 2 diabetes, cancer, neurodegenerative and cardiovascular diseases and even septic shock. During an innate immune response, antimicrobial peptides and cytokines are trafficked via Rab11 multivesicular endosomes, and then sorted into Rab11 vesicles for traffic to the plasma membrane and secretion. In this study, a cyclin-dependent kinase inhibitor CDKI-73 was used to determine its effect on the innate immune response, based on previously identified targets for this compound. Our results showed that CDKI-73 inhibited the delivery of Rab11 vesicles to the plasma membrane, resulting in the accumulation of large multivesicular Rab11 endosomes near the cell periphery. In addition to the effect on endosome delivery, CDKI-73 down-regulated the amount of innate immune cargo, including the antimicrobial peptide Drosomycin and pro-inflammatory cytokines interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFα). We concluded that CDKI-73 has the potential to regulate the delivery and secretion of certain innate immune cargo, which could be used to control inflammation.

Assessing the toxicant effect of spontaneously volatilized 4-vinylcyclohexane exposure in nymphs of the lobster cockroach nauphoeta cinerea.

Vinylcyclohexene (VCH) is an environmental contaminant well known for its ovotoxicant effects in several organisms. However, the mechanisms underlying the toxicity of VCH as well as its harmful effects toward other organs are until unclear. In this work, we assess some endpoint signals of toxicity induced by volatilized VCH exposure using nymphs of the lobster cockroach Nauphoeta cinerea. Nymphs were exposed to VCH via inhalation for 70 days. The levels of volatilized VCH were quantified by headspace gas chromatography and the concentration varied between 3.41 and 7.03 nmol/µl. VCH inhalation caused a reduction of 35% in the survival rate of the exposed animals. Nymphs exposed to volatilized VCH for 35 and 70 days had a reduction in the body weight gain of 1.8- and 2.6-fold, respectively with a reduction in dissected head, fat body, and maturing reproductive organs. The exposure did not change water consumption, excepting on the 20th day (with a 3-fold change) and decreased the food intake significantly. Regarding biochemical markers, we found that the activity of GST from the dissected organs was increased by volatilized VCH after both 35 and 70 days of exposure. The fat body presented the most prominent GST activity especially after 35 days of exposure with 1.6-fold higher than the control group. Exposure also caused an increase in RS levels in the fat body of 1.35-fold and 1.47-fold after 35 and 70 days, respectively and did not affect the activity of the AChE from the head. Our findings support the harmful impact of volatilized VCH inhalation, highlighting the cockroach N.cinerea as a valuable insect model to investigate environmental toxicants.

Cytotoxicity of Piper aduncum (Piperaceae) essential oil in brown stink bug Euschistus heros (Heteroptera: Pentatomidae).

Euschistus heros (F.) (Hemiptera: Pentatomidae) is a soybean pest in Brazil, controlled with synthetic chemical insecticides, which may be harmful to the environment and humans, as well as to select pest resistant strains. The research for new pest control strategies such as the use of plant essential oils has been increased due to the selectivity and biodegradation of these molecules. The objective was to evaluate the cytological changes in the salivary glands, fat body and midgut of E. heros exposed to different concentrations of essential oil of Piper aduncum L. (Piperales: Piperaceae), which the main compounds were identified as myristicin 30.03%, aromadendrene 9.20%, dillapiole 8.43%, α-serinene 7.31%, tridecane 6.26%, γ-elemene 4.58% and o-cymene 4.20%. The essential oil of P. aduncum was toxic for E. heros with LD50 = 36.23 mg per insect and LD90 = 50.42 mg per insect. Cytological changes such as tissue disruption, increase in mitochondria population, and glycogen and lipid depletion occur in the fat body cells, whereas salivary glands and midgut are not affected by this essential oil. Results suggest that P. aduncum essential oil causes fat body cellular stress, which may compromise some physiological processes for the insect survival.

Anti-tumour effects of antimicrobial peptides, components of the innate immune system, against haematopoietic tumours in Drosophila mxc mutants.

The innate immune response is the first line of defence against microbial infections. In Drosophila, two major pathways of the innate immune system (the Toll- and Imd-mediated pathways) induce the synthesis of antimicrobial peptides (AMPs) within the fat body. Recently, it has been reported that certain cationic AMPs exhibit selective cytotoxicity against human cancer cells; however, little is known about their anti-tumour effects. Drosophila mxcmbn1 mutants exhibit malignant hyperplasia in a larval haematopoietic organ called the lymph gland (LG). Here, using RNA-seq analysis, we found many immunoresponsive genes, including those encoding AMPs, to be upregulated in these mutants. Downregulation of these pathways by either a Toll or imd mutation enhanced the tumour phenotype of the mxc mutants. Conversely, ectopic expression of each of five different AMPs in the fat body significantly suppressed the LG hyperplasia phenotype in the mutants. Thus, we propose that the Drosophila innate immune system can suppress the progression of haematopoietic tumours by inducing AMP gene expression. Overexpression of any one of the five AMPs studied resulted in enhanced apoptosis in mutant LGs, whereas no apoptotic signals were detected in controls. We observed that two AMPs, Drosomycin and Defensin, were taken up by circulating haemocyte-like cells, which were associated with the LG regions and showed reduced cell-to-cell adhesion in the mutants. By contrast, the AMP Diptericin was directly localised at the tumour site without intermediating haemocytes. These results suggest that AMPs have a specific cytotoxic effect that enhances apoptosis exclusively in the tumour cells.

Insecticide activity of Curcuma longa (leaves) essential oil and its major compound α-phellandrene against Lucilia cuprina larvae (Diptera: Calliphoridae): Histological and ultrastructural biomarkers assessment.

Lucilia cuprina, known as the Australian blowfly, is of high medico-sanitary and veterinary importance due to its ability to induce myiasis. Synthetic products are the most frequent form of fly control, but their indiscriminate use has selected for resistant populations and accounted for high levels of residues in animal products. This study aimed to assess the effect of essential oil from leaves of Curcuma longa (CLLEO), and its major compound α-phellandrene against L. cuprina L3. An additional goal was to determine the morphological alterations in target organs/tissues through ultrastructural assessment (SEM) and light microscopy, as well as macroscopic damage to cuticle induced by CLLEO. Groups of 20 L3 were placed on filter paper impregnated with increasing concentrations of CLLEO (0.15 to 2.86 µL/cm2) and α-phellandrene (0.29 to 1.47 µL/cm2). Efficacy was determined by quantifying L3 mortality 6, 24 and 48 h after contact with CLLEO and by measuring the structural damage to L3. CLLEO and α-phellandrene inhibited adult emergence by 96.22 and 100%, respectively. Macroscopic cuticle damage, appeared as diffuse pigment and darkening of larval body, was caused by both extracts. The SEM revealed dryness on the cuticle surface, distortion of the sensorial structures and general degeneration in treated L3. Furthermore, alterations in target organs (digestive tract, fat body and brain) were noticed and shall be used as biomarkers in future attempts to elucidate the mechanism of action of these compounds. The vacuolar degeneration and pyknotic profiles observed in the brain tissue of treated larvae with both extracts and the decreased motility within <6 h after treatment leads us to suggest a neurotoxic activity of the products. This work demonstrates the potential use of CLLEO and α-phellandrene as bioinsecticides to be used against L. cuprina, representing an ecofriendly alternative for myiasis control in humans and animals.

Exogenous substances regulate silkworm fat body protein synthesis through MAPK and PI3K/Akt signaling pathways.

Insect fat body is an important intermediate metabolic organ that plays an important role in protein metabolism and detoxification. In order to study the effects of TiO2 NPs and phoxim on fat body protein synthesis through MAPK and PI3K/Akt signaling pathways in silkworms, we determined the effects of TiO2 NPs and phoxim, alone and in combination, on fat body protein content of silkworms, analyzed the gene expression profile of the fat body, and verified the expression of characteristic genes. We found that TiO2 NPs and phoxim alone increased the total protein content of the fat body, and up-regulated MAPK and PI3K/Akt signaling pathway genes. TiO2 NPs up-regulated the expression of two growth and development-related genes-insulin-like peptide and neuropeptide receptor B-by 5.17 and 3.89-fold, respectively. Phoxim up-regulated the expression of detoxification genes-P450, GST, and CarE2. Pretreatment with TiO2 NPs could reduce phoxim-increased total protein content and up-regulated MAPK and PI3K/Akt signaling pathway genes and detoxification genes; the activities of detoxification enzymes were consistent with the gene expression pattern. Our results showed that MAPK and PI3K/Akt signaling pathways both regulate fat body protein synthesis in silkworms, but the target proteins induced to express were different under different inducing factors. Our finding may provide a reference for investigating the mechanism of protein synthesis regulation through MAPK and PI3K/Akt signaling pathways.

Alterations in the oxidative metabolism of Rhipicephalus (Boophilus) microplus ticks in response to exposure to the insect growth regulator fluazuron / Alterações no metabolismo oxidativo de carrapatos Rhipicephalus (Boophilus) microplus em resposta à exposição ao regulador de crescimento fluazuron

Abstract Aiming to characterize the potential off-target effects of fluazuron on ticks, biochemical analyses were conducted to evaluate changes in the carbohydrate metabolism of Rhipicephalus (Boophilus) microplus ticks after exposure to fluazuron. Hemolymph and fat body were collected from female ticks before and after (4, 8 and 15 days) exposure to fluazuron. Spectrophotometric analyses were done to quantify glucose concentration and lactate dehydrogenase (LDH) activity in the hemolymph and the concentration of glycogen in the tick’s fat body. High Performance Liquid Chromatography (HPLC) was employed to determine the concentration of carboxylic acids in the hemolymph and to evaluate changes in intermediary metabolic processes requiring oxygen consumption. Increases in the levels of LDH activity and lactic acid concentration indicated that fluazuron enhanced fermentative metabolism in ticks. Exposure to fluazuron was also found to increase glucose concentrations in the hemolymph over time, although no significant differences were noted daily. In addition to expanding the body of knowledge about the mode of action of fluazuron, investigations into these mechanisms may also be useful in discovering new and as yet unexplored secondary effects.

Resumo Com o objetivo de caracterizar os efeitos não-alvo da ação do fluazuron, foram realizados testes bioquímicos para analisar possíveis alterações no metabolismo de carboidratos em carrapatos Rhipicephalus (Boophilus) microplus após sua exposição ao composto. Foram coletados hemolinfa e corpo gorduroso de fêmeas ingurgitadas antes e após (4, 8 e 15 dias) a exposição ao fluazuron. Análises espectrofotométricas foram usadas para quantificar a concentração de glicose e a atividade da lactato desidrogenase (LDH) na hemolinfa e concentração de glicogênio no corpo gorduroso. Cromatografia Líquida de Alta Eficiência (CLAE) foi usada para determinação das concentrações de ácidos carboxílicos na hemolinfa e avaliar possíveis alterações em metabolismo intermediário em relação ao consumo de oxigênio. Aumento na atividade de LDH e concentração de ácido lático indicaram que o fluazuron pode regular o metabolismo fermentativo em carrapatos. A exposição ao fluazuron também aumentou a concentração de glicose na hemolinfa, apesar de não ter havido diferença significativa na comparação entre as médias no mesmo dia de avaliação. Além de aumentar o conhecimento sobre o modo de ação do fluazuron, investigações sobre tais mecanismos também são úteis no descobrimento de novos efeitos secundários ainda não explorados.

AUTEN-67, an autophagy-enhancing drug candidate with potent antiaging and neuroprotective effects.

Autophagy is a major molecular mechanism that eliminates cellular damage in eukaryotic organisms. Basal levels of autophagy are required for maintaining cellular homeostasis and functioning. Defects in the autophagic process are implicated in the development of various age-dependent pathologies including cancer and neurodegenerative diseases, as well as in accelerated aging. Genetic activation of autophagy has been shown to retard the accumulation of damaged cytoplasmic constituents, delay the incidence of age-dependent diseases, and extend life span in genetic models. This implies that autophagy serves as a therapeutic target in treating such pathologies. Although several autophagy-inducing chemical agents have been identified, the majority of them operate upstream of the core autophagic process, thereby exerting undesired side effects. Here, we screened a small-molecule library for specific inhibitors of MTMR14, a myotubularin-related phosphatase antagonizing the formation of autophagic membrane structures, and isolated AUTEN-67 (autophagy enhancer-67) that significantly increases autophagic flux in cell lines and in vivo models. AUTEN-67 promotes longevity and protects neurons from undergoing stress-induced cell death. It also restores nesting behavior in a murine model of Alzheimer disease, without apparent side effects. Thus, AUTEN-67 is a potent drug candidate for treating autophagy-related diseases.

Comparisons of topical and spray applications of two pesticides, triazophos and jinggangmycin, on the protein content in the ovaries and fat bodies of the brown planthopper Nilaparvata lugens Stål (Hemiptera:Delphacidae).

The pesticide-induced stimulation of reproduction in pests is one of the most important mechanisms of pest resurgence. There have been numerous reports on the insecticide-induced stimulation of reproduction. However, the relationship between pesticide application method and pest resurgence (stimulation of reproduction) has received little attention. Here, we studied the effect of two treatment methods, triazophos (TZP) and jinggangmycin (JGM), on the protein content in the ovaries and fat bodies of the brown planthopper (BPH) Nilaparvata lugens Stål. The results showed that pesticide treatment methods significantly affected the protein content in the ovaries and fat bodies of BPH. In addition, grand means (means of main effect) of the protein content at 2 and 3 days after emergence (2 and 3 DAE) for foliar sprays was significantly higher than that observed after topical treatments, which increased by 23.9% (from 1.42 to 1.76) and 8.82% (from 4.42 to 4.81), respectively. No significant differences on the protein content in the ovaries and fat bodies for the JGM topical treatment were observed compared with controls. However, the protein content for JGM foliar sprays was significantly higher than that for the controls. The protein contents in both topical and spray treatments of TZP were significantly higher than those of the controls. Ovarian protein is mainly yolk protein. There is a positive correlation between ovarian protein content and the number of eggs laid. These findings show that foliar spray of the pesticides promotes the resurgence of BPH. Therefore, the foliar spray of some pesticides, such as JGM, should be avoided for the control of pests, which is the sideeffects of the fungicide on non-target insect pests' occurrence.

Molecular analysis of Aedes aegypti classical protein tyrosine phosphatases uncovers an ortholog of mammalian PTP-1B implicated in the control of egg production in mosquitoes.

BACKGROUND: Protein Tyrosine Phosphatases (PTPs) are enzymes that catalyze phosphotyrosine dephosphorylation and modulate cell differentiation, growth and metabolism. In mammals, PTPs play a key role in the modulation of canonical pathways involved in metabolism and immunity. PTP1B is the prototype member of classical PTPs and a major target for treating human diseases, such as cancer, obesity and diabetes. These signaling enzymes are, hence, targets of a wide array of inhibitors. Anautogenous mosquitoes rely on blood meals to lay eggs and are vectors of the most prevalent human diseases. Identifying the mosquito ortholog of PTP1B and determining its involvement in egg production is, therefore, important in the search for a novel and crucial target for vector control. METHODOLOGY/PRINCIPAL FINDINGS: We conducted an analysis to identify the ortholog of mammalian PTP1B in the Aedes aegypti genome. We identified eight genes coding for classical PTPs. In silico structural and functional analyses of proteins coded by such genes revealed that four of these code for catalytically active enzymes. Among the four genes coding for active PTPs, AAEL001919 exhibits the greatest degree of homology with the mammalian PTP1B. Next, we evaluated the role of this enzyme in egg formation. Blood feeding largely affects AAEL001919 expression, especially in the fat body and ovaries. These tissues are critically involved in the synthesis and storage of vitellogenin, the major yolk protein. Including the classical PTP inhibitor sodium orthovanadate or the PTP substrate DiFMUP in the blood meal decreased vitellogenin synthesis and egg production. Similarly, silencing AAEL001919 using RNA interference (RNAi) assays resulted in 30% suppression of egg production. CONCLUSIONS/SIGNIFICANCE: The data reported herein implicate, for the first time, a gene that codes for a classical PTP in mosquito egg formation. These findings raise the possibility that this class of enzymes may be used as novel targets to block egg formation in mosquitoes.

Antioxidative capacity in the fat body of Bombyx mori is increased following oral administration of 4-methylumbelliferone.

Plant sources of umbelliferones have tumor-inhibitory effects at the cellular level. However, their physiological functions in animals are largely unresolved. In this study, we provide evidence to show that 4-methylumbelliferone (4-MU) participates in the regulation of antioxidative capacity in the fat body of Bombyx mori, a tissue similar to mammalian liver in this model invertebrate. Larvae (3rd day of the 5th instar) were orally exposed to 4 mM 4-MU, an umbelliferone, which swiftly induced the generation of a large number of ROS (e.g. H2O2 increased 6 to 8-fold), and 4-MU was detected in the fat body 8 min after administration. In addition, the activities of CAT and GPx were up-regulated 4 to 11-fold and 2 to 16-fold, respectively, and were helpful in defending fat body cells against oxidative injury in combination with NADPH. Furthermore, significant increases in the contents of T-AOC (up to approx. 2-fold), antioxidants of ASAFR (by 2 to 4-fold) and GSH were detected.

Biochemical and histological effects of gibberellic acid on Locusta migratoria migratoria fifth instar larvae.

Experiments were conducted to assess the effect of gibberellic acid (GA3), a plant growth regulator, on Locusta migratoria migratoria fifth instar larvae. Newly emerged larvae were exposed to various concentrations of GA3 administered by topical application or by forced ingestion. Results showed that treated insects exhibited toxic symptoms with a dose-dependent mortality. GA3 toxicity was also demonstrated by perturbation of the moult processes. In fact, we noted that treated insects present exuviations difficulties due to the impossibility to reject the old integuments causing mortality in the 5th instar larvae. Histological study of proventriculus revealed alterations in the epithelial cells and absence of apolysis phenomenon. Data also showed that GA3 induced significant quantitative variation of haemolymph metabolites. These changes result in a significant decrease in the total concentration of proteins and carbohydrates and an increase in the total concentration of haemolymph lipids.

Screening and identification of dietary oils and unsaturated fatty acids in inhibiting inflammatory prostaglandin E2 signaling in fat stromal cells.

BACKGROUND: The molecular mechanisms of dietary oils (such as fish oil) and unsaturated fatty acids, which are widely used by the public for anti-inflammation and vascular protection, have not been settled yet. In this study, prostaglandin E(2) (PGE(2))-mediated calcium signaling was used to screen dietary oils and eight unsaturated fatty acids for identification of their anti-inflammatory mechanisms. Isolated fat/stromal cells expressing endogenous PGE(2) receptors and an HEK293 cell line specifically expressing the recombinant human PGE(2) receptor subtype-1 (EP(1)) were cultured and used in live cell calcium signaling assays. The different dietary oils and unsaturated fatty acids were used to affect cell signaling under the specific stimulation of a pathological amount of inflammatory PGE(2). RESULTS: It was identified that fish oil best inhibited the PGE(2) signaling in the primary cultured stromal cells. Second, docosahexaenoic acid (DHA), found in abundance in fish oil, was identified as a key factor of inhibition of PGE(2) signaling. Eicosapentaenoic acid (EPA), another major fatty acid found in fish oil and tested in this study was found to have small effect on EP(1) signaling. The study suggested one of the four PGE(2) subtype receptors, EP(1) as the key target for the fish oil and DHA target. These findings were further confirmed by using the recombinant EP(1) expressed in HEK293 cells as a target. CONCLUSION: This study demonstrated the new mechanism behind the positive effects of dietary fish oils in inhibiting inflammation originates from the rich concentration of DHA, which can directly inhibit the inflammatory EP(1)-mediated PGE(2) receptor signaling, and that the inflammatory response stimulated by PGE(2) in the fat stromal cells, which directly related to metabolic diseases, could be down regulated by fish oil and DHA. These findings also provided direct evidence to support the use of dietary oils and unsaturated fatty acids for protection against heart disease, pain, and cancer resulted from inflammatory PGE(2).

Alteration of carbohydrates metabolism and midgut glucose absorption in Gromphadorhina portentosa after subchronic exposure to imidacloprid and fenitrothion.

This study was undertaken to test the hypothesis that following exposure to insecticides, changes take place in the metabolism of carbohydrates and absorption in the midgut of insects. The Madagascar hissing cockroach (Gromphadorhina portentosa) was chosen for the experiment as a model organism, due to it being easy to breed and its relatively large alimentary tract, which was important when preparing the microperfusion midgut bioassay. In each group of cockroaches treated with imidacloprid and fenitrothion, absorption of glucose, expressed as the area under the curve (AUC), was elevated compared to the control group. Glucose in the hemolymph of the examined insects was present in a vestigial amount, often below the threshold of determination, so the determinable carbohydrate indices were: hemolymph trehalose concentration and fat body glycogen content. The level of trehalose found in the hemolymph of insects when exposed to fenitrothion, and irrespective of the level of concentration mixed into food, were significantly lower when comparing to the control samples. Imidacloprid acted analogically with one exception at the concentration of 10 mg·kg(-1) dry food where trehalose concentration did not differ from the control values. Coupling with fat body glycogen concentration was less visible and appeared only at the concentrations of 5 and 10 mg imidacloprid·kg(-1) dry food. As described in this study changes in the sugar distribution and midgut glucose absorption indicate that insects cover the increased energy needs induced by insecticides; also at the gastrointestinal tract level. The result indicates that the midgut glucose absorption parameters could be considered as a non-specific biomarker of insecticide toxicity.

Royalactin induces queen differentiation in honeybees.

The honeybee (Apis mellifera) forms two female castes: the queen and the worker. This dimorphism depends not on genetic differences, but on ingestion of royal jelly, although the mechanism through which royal jelly regulates caste differentiation has long remained unknown. Here I show that a 57-kDa protein in royal jelly, previously designated as royalactin, induces the differentiation of honeybee larvae into queens. Royalactin increased body size and ovary development and shortened developmental time in honeybees. Surprisingly, it also showed similar effects in the fruitfly (Drosophila melanogaster). Mechanistic studies revealed that royalactin activated p70 S6 kinase, which was responsible for the increase of body size, increased the activity of mitogen-activated protein kinase, which was involved in the decreased developmental time, and increased the titre of juvenile hormone, an essential hormone for ovary development. Knockdown of epidermal growth factor receptor (Egfr) expression in the fat body of honeybees and fruitflies resulted in a defect of all phenotypes induced by royalactin, showing that Egfr mediates these actions. These findings indicate that a specific factor in royal jelly, royalactin, drives queen development through an Egfr-mediated signalling pathway.

Fat cells reactivate quiescent neuroblasts via TOR and glial insulin relays in Drosophila.

Many stem, progenitor and cancer cells undergo periods of mitotic quiescence from which they can be reactivated. The signals triggering entry into and exit from this reversible dormant state are not well understood. In the developing Drosophila central nervous system, multipotent self-renewing progenitors called neuroblasts undergo quiescence in a stereotypical spatiotemporal pattern. Entry into quiescence is regulated by Hox proteins and an internal neuroblast timer. Exit from quiescence (reactivation) is subject to a nutritional checkpoint requiring dietary amino acids. Organ co-cultures also implicate an unidentified signal from an adipose/hepatic-like tissue called the fat body. Here we provide in vivo evidence that Slimfast amino-acid sensing and Target of rapamycin (TOR) signalling activate a fat-body-derived signal (FDS) required for neuroblast reactivation. Downstream of this signal, Insulin-like receptor signalling and the Phosphatidylinositol 3-kinase (PI3K)/TOR network are required in neuroblasts for exit from quiescence. We demonstrate that nutritionally regulated glial cells provide the source of Insulin-like peptides (ILPs) relevant for timely neuroblast reactivation but not for overall larval growth. Conversely, ILPs secreted into the haemolymph by median neurosecretory cells systemically control organismal size but do not reactivate neuroblasts. Drosophila thus contains two segregated ILP pools, one regulating proliferation within the central nervous system and the other controlling tissue growth systemically. Our findings support a model in which amino acids trigger the cell cycle re-entry of neural progenitors via a fat-body-glia-neuroblasts relay. This mechanism indicates that dietary nutrients and remote organs, as well as local niches, are key regulators of transitions in stem-cell behaviour.