Neurosecretory Cells Of Brain Research Articles

Dietary compounds activate an insect gustatory receptor on enteroendocrine cells to elicit myosuppressin secretion.

Sensing of midgut internal contents is important for ensuring appropriate hormonal response and digestion following the ingestion of dietary components. Studies in mammals have demonstrated that taste receptors (TRs), a subgroup of G protein-coupled receptors (GPCRs), are expressed in gut enteroendocrine cells (EECs) to sense dietary compounds and regulate the production and/or secretion of peptide hormones. Although progress has been made in identifying expression patterns of gustatory receptors (GRs) in gut EECs, it is currently unknown whether these receptors, which act as ligand-gated ion channels, serve similar functions as mammalian GPCR TRs to elicit hormone production and/or secretion. A Bombyx mori Gr, BmGr6, has been demonstrated to express in cells by oral sensory organs, midgut and nervous system; and to sense isoquercitrin and chlorogenic acid, which are non-nutritional secondary metabolites of host mulberry. Here, we show that BmGr6 co-expresses with Bommo-myosuppressin (BMS) in midgut EECs, responds to dietary compounds and is involved in regulation of BMS secretion. The presence of dietary compounds in midgut lumen after food intake resulted in an increase of BMS secretions in hemolymph of both wild-type and BmGr9 knockout larvae, but BMS secretions in BmGr6 knockout larvae decreased relative to wild-type. In addition, loss of BmGr6 led to a significant decrease in weight gain, excrement, hemolymph carbohydrates levels and hemolymph lipid levels. Interestingly, although BMS is produced in both midgut EECs and brain neurosecretory cells (NSCs), BMS levels in tissue extracts suggested that the increase in hemolymph BMS during feeding conditions is primarily due to secretion from midgut EECs. Our studies indicate that BmGr6 expressed in midgut EECs responds to the presence of dietary compounds in the lumen by eliciting BMS secretion in B. mori larvae.

Differential expression of ITP and ITPL indicate multiple functions in the silkworm Bombyx mori.

Ion transport peptide (ITP) and a longer ITP-like (ITPL) are alternatively spliced insect neuropeptides involved in the regulation of development and water homeostasis. Using in situ hybridisation and immunohistochemistry, we determined site- and stage-specific expression of each peptide in Bombyx mori. Each peptide was differentially expressed, except for the prominent overlapping expression of both peptides in six pairs of the brain neurosecretory cells Ia2. After metamorphosis, ITP appeared in the male-specific neurons of the abdominal neuromere 9 (MAN9) that innervate the reproductive organs. ITPL was detected in a pair of dorsolateral interneurons (IN-DL) in each thoracic and abdominal ganglion, and in the thoracic neurosecretory cells (NS-VTL2) which terminate in the vicinity of the prothoracic gland. Feeding larvae showed ITPL expression in the abdominal neurosecretory cells M5. ITPL was also expressed in the peripheral L1 neurons that project axons into the thoracic and abdominal transverse nerves. Our results suggest that ITP and ITPL exhibit different sex- and stage-specific functions that may include regulation of reproduction and steroid production. For future functional studies, we identified an upstream regulatory region controlling ITP/ITPL expression in the brain and L1 neurons, and prepared stable transgenic line pITP-Gal4.2 using the piggyBac system.

BmGr4 responds to sucrose and glucose and expresses in tachykinin-related peptide-secreting enteroendocrine cells

The regulatory hormones known as tachykinin-related peptides (TRPs) are identified as brain-gut peptides in insects. Dietary components from mulberry leaves, including glucose, induce secretion of TRPs from Bombyx mori midgut. However, the sensory molecules that recognize these compounds are still unknown. Here, we identified the gustatory receptor, BmGr4, as a sucrose and glucose receptor using Ca2+ imaging. Immunostaining revealed BmGr4 expression not only in the midgut, but also in the brain. In addition, BmGr4 expression was found to co-localize with TRP-expressing cells in both midgut enteroendocrine cells (EECs) and brain neurosecretory cells (NSCs). Furthermore, dietary nutrients after food intake result in an increase of TRP-level in hemolymph of silkworm larvae. These results provide significant circumstantial evidence for the involvement of the sucrose and glucose receptor, BmGr4, in the elicitation of TRP secretion in midgut EECs and brain NSCs.

Parasite reliance on its host gut microbiota for nutrition and survival

Studying the microbial symbionts of eukaryotic hosts has revealed a range of interactions that benefit host biology. Most eukaryotes are also infected by parasites that adversely affect host biology for their own benefit. However, it is largely unclear whether the ability of parasites to develop in hosts also depends on host-associated symbionts, e.g., the gut microbiota. Here, we studied the parasitic wasp Leptopilina boulardi (Lb) and its host Drosophila melanogaster. Results showed that Lb successfully develops in conventional hosts (CN) with a gut microbiota but fails to develop in axenic hosts (AX) without a gut microbiota. We determined that developing Lb larvae consume fat body cells that store lipids. We also determined that much larger amounts of lipid accumulate in fat body cells of parasitized CN hosts than parasitized AX hosts. CN hosts parasitized by Lb exhibited large increases in the abundance of the bacterium Acetobacter pomorum in the gut, but did not affect the abundance of Lactobacillus fructivorans which is another common member of the host gut microbiota. However, AX hosts inoculated with A. pomorum and/or L. fructivorans did not rescue development of Lb. In contrast, AX larvae inoculated with A. pomorum plus other identified gut community members including a Bacillus sp. substantially rescued Lb development. Rescue was further associated with increased lipid accumulation in host fat body cells. Insulin-like peptides increased in brain neurosecretory cells of parasitized CN larvae. Lipid accumulation in the fat body of CN hosts was further associated with reduced Bmm lipase activity mediated by insulin/insulin-like growth factor signaling (IIS). Altogether, our results identify a previously unknown role for the gut microbiota in defining host permissiveness for a parasite. Our findings also identify a new paradigm for parasite manipulation of host metabolism that depends on insulin signaling and the gut microbiota.

A local insulin reservoir in Drosophila alpha cell homologs ensures developmental progression under nutrient shortage

Insulin/insulin-like growth factor (IGF) signaling (IIS) controls many aspects of development and physiology. In Drosophila, a conserved family of insulin-like peptides called Dilps is produced by brain neurosecretory cells, and it regulates organismal growth and developmental timing. To accomplish these systemic functions, the Dilps are secreted into the general circulation, and they signal to peripheral tissues in an endocrine fashion. Here, we describe the local uptake and storage of Dilps in the corpora cardiaca (CC), an endocrine organ composed of alpha cell homologs known to produce the glucagon-like adipokinetic hormone (AKH). We show that Dilp uptake by the CC relies on the expression of an IGF-binding protein called ImpL2. Following their uptake, immunogold staining demonstrates that Dilps are co-packaged with AKH in dense-core vesicles for secretion. In response to nutrient shortage, this specific Dilp reservoir is released and activates IIS in a paracrine manner in the prothoracic gland. This stimulates the production of the steroid hormone ecdysone and initiates entry into pupal development. We therefore uncover a sparing mechanism whereby insulin stores in CC serve to locally activate IIS and the production of ecdysone in the PG, accelerating developmental progression in adverse food conditions.

The adverse effects of injected functionalized multi-walled carbon nanotube (f-MWCNT) on in vivo neurosecretory brain cells of Jamaican field cricket, Gryllus assimilis.

Carbon nanotubes (CNTs) have been increasingly more prevalent due to their use in product technology owing to their exceptional electrical and thermal conductivity and tensile strength because of their nanostructure and strength of the bonds among carbon atoms. The potential increase of CNTs in the environment is a concern, and studies to assess the toxic effects of these nanomaterials (NMs) are needed. However, so far, most of the studies are focused on aquatic species and much less is understood about the effects of NM in terrestrial organisms. This investigation used a functionalized multi-walled carbon nanotube (f-MWCNT) and the Jamaican cricket Gryllus assimilis to assess the effects of this NM. Cricket nymphs were injected with f-MWCNT suspension-at three different concentrations. The insecticide Fipronil was used as a positive control. Survival was monitored, and histological analysis was made in the brains. Pyknotic cells were quantified in two brain regions, a neurosecretory called Pars intercerebralis (PI), and an associative region called mushroom body (MB). No mortality was observed in any f-MWCNT concentration tested. A significant increase in pyknotic cells was observed as sub-lethal effect for the intermediate concentration of f-MWCNT, at PI, while any significant change was observed at the Kenyon cells of the MB. These results are discussed in the context of agglomeration and dispersion of the f-MWCNT at different concentrations, and availability of the f-MWCNT on the circulatory system, as well as the natural decay of pyknotic cells with time and different patterns of adult cricket neurogenesis. Our results showed that f-MWCNT had negative effects in the neurosecretory region of the brain.

Neuroendocrine control of cocoon production in native earthworm Perionyx ceylanensis subjected to seasonal variation

Aim: The aim of the present study was to observe the role of cerebral ganglionic neurosecretory cells (NSCs) during cocoon production in native earthworm species Perionyx ceylanensis subjected to amputation and seasonal variations. Methodology: Histological studies (using Aldehyde Fuchsin and Chrome Alum Haematoxylin Phloxin stain) were carried out on brain NSCs in the two groups of earthworms (Group I and Group II) maintained in earthen culture pots (2L) with cowdung as food. Group I comprised of brain amputed earthworms was subjected to observe the role of brain NSCs in production of cocoon and Group II earthworms subjected to seasonal changes in the cerebral NSCs during cocoon production. Five replications were kept for Group I (1 individual per pot) and Group II (1 pair per pot). Results: Group I debrained earthworms started to lay cocoons from the 31st day following regeneration of cerebral ganglionic type A NSCs. In group II worms the highest neurosecretory activity was registered in the cerebral type A cells, especially during monsoon coinciding with the hike of cocoon generation. Interpretation: Appearance of type A NSCs in regenerated brain and peak of type A neurosecretory cell activity during peak reproductive period of earthworm species (as indicated by peak of cocoon production) indicates the possible role of cerebral type A NSCs in cocoon laying.

Immunocytochemical localization of leptin hormone in the neurosecretory cells of brain–suboesophageal ganglion complex of tropical tasar silkworm, Antheraea mylitta (D.) eco-race Bhandara

Immunocytochemical localization of leptin hormone in the neurosecretory cells of brain–suboesophageal ganglion complex of tropical tasar silkworm, Antheraea mylitta (D.) eco-race Bhandara

Resolving Transcriptional States and Predicting Lineages in the Annelid Capitella teleta Using Single-Cell RNAseq

Evolution and diversification of cell types has contributed to animal evolution. However, gene regulatory mechanisms underlying cell fate acquisition during development remains largely uncharacterized in spiralians. Here we use a whole-organism, single-cell transcriptomic approach to map larval cell types in the annelid Capitella teleta at 24- and 48-h post gastrulation (stages 4 and 5). We identified eight unique cell clusters (undifferentiated precursors, ectoderm, muscle, ciliary-band, gut, neurons, neurosecretory cells, and protonephridia), thus helping to identify uncharacterized molecular signatures such as previously unknown neurosecretory cell markers in C. teleta. Analysis of coregulatory programs in individual clusters revealed gene interactions that can be used for comparisons of cell types across taxa. We examined the neural and neurosecretory clusters more deeply and characterized a differentiation trajectory starting from dividing precursors to neurons using Monocle3 and velocyto. Pseudotime analysis along this trajectory identified temporally-distinct cell states undergoing progressive gene expression changes over time. Our data revealed two potentially distinct neural differentiation trajectories including an early trajectory for brain neurosecretory cells. This work provides a valuable resource for future functional investigations to better understanding neurogenesis and the transitions from neural precursors to neurons in an annelid.

Histological investigation of the effects of fenoxycarb on neurosecretory cells in the silkworm, Bombyx mori brain.

Fenoxycarb 0-ethyl N-(2-(4-pheoxyphenoxy)-ethyl) carbamate is the most potent juvenile hormone analogue against a variety of insect species including the silkworm Bombyx mori. In this study, the effects of fenoxycarb on silkworm Bombyx mori brain neurosecretory cells in 5th instar were investigated. Fenoxycarb (1ng/10µl) was applied topically along the dorsa-medial line to the animals in the spinning behavior on day 1 of the experimental group. Brains removed by dissection were histologically examined by hematoxylin eosin (hem&eosin) and paraldehyde fuchsin staining. Three types of neurosecretory cells (NSCs) were identified, NSC-1, NSC-2 and NSC-3. It was determined that cell secretions were in different density on different days. It was shown that the secretion density of cells on different days was not the same as the experimental and control groups. The fenoxycarb was found to suppress the bombyxin (insulin-like peptides) secretion of cells in the spinning behavior on day 2. Also, it stimulated the division of NSCs on the spinning behavior on day 5.

Proline‑rich polypeptide‑1 decreases cancer stem cell population by targeting BAFF chromatin‑remodeling complexes in human chondrosarcoma JJ012 cells.

Chondrosarcoma is the second most common primary malignant bone tumor and is resistant to chemotherapy and radiation. Inadequate treatment response and poor prognosis requires novel therapeutic approaches. Proline‑rich polypeptide‑1 (PRP‑1), synthesized by brain neurosecretory cells, has demonstrated antitumor properties in JJ012‑cells; however, its underlying molecular mechanism remains unclear. The present study aimed to investigate the epigenetic regulation by which PRP‑1 inhibits chondrosarcoma cancer stem cell (CSC) proliferation and to elucidate additional CSC biomarkers in human chondrosarcoma other than ALDH1A1. Human chondrosarcoma JJ012‑cells were treated with PRP‑1 prior to performing an Aldefluor™ assay and fluorescence‑activated cell sorting in order to determine aldehyde dehydrogenase (ALDH) expression levels and isolate ALDHhigh and ALDHlow cell populations. ALDH is an established marker of CSCs in several neoplasms, including chondrosarcoma. The cells were collected and lysed for gel electrophoresis, followed by western blot analysis. The Aldefluor™ assay was used to assess the expression levels of well‑established CSC biomarkers, including CD133, CD4, CD10, CD144, CD177, CD221, CD271, leucine‑rich repeat‑containing G protein‑coupled receptor 5, SOX2 and B lymphoma Mo‑MLV insertion region 1 homolog (BMI‑1), within the ALDHhigh population of JJ012 cells. The results confirmed that ALDHA1 was the biomarker for chondrosarcoma CSCs. PRP‑1 was demonstrated to inhibit the ALDHhigh population colony and sarcosphere formation; 5µg/ml PRP‑1 was indicated to be the optimum concentration in eliminating colonies formed by JJ012 cells (92%, P<0.001) and by the ALDHhigh CSC‑population (80.5%, P<0.001) in the clonogenic dose‑response assay. Spheroid growth unequivocally decreased with an increase in PRP‑1 dose. In order to determine the molecular mechanism by which PRP‑1 decreased the CSC population, the regulation of the mammalian Switch/sucrose non‑fermenting (SWI/SNF) complex, also referred to as BRG1‑associated factor (BAF) complex, which either activates or represses transcription, thus acting as an oncogene or tumor suppressor in human cells, was analyzed. PRP‑1 was demonstrated to decrease the expression levels of BRG, BAF170 and BRM; therefore, in JJ012 cells, these key players of the SWI/SNF (BAF) complex served an oncogenic role. The results of the present study demonstrated that PRP‑1 targets chromatin‑remodeling complexes; therefore, future efforts will be directed towards determining the interconnection between CSC maintenance, self‑renewal capacity and BAF complexes.

Regulatory Roles of Drosophila Insulin-Like Peptide 1 (DILP1) in Metabolism Differ in Pupal and Adult Stages.

The insulin/IGF-signaling pathway is central in control of nutrient-dependent growth during development, and in adult physiology and longevity. Eight insulin-like peptides (DILP1–8) have been identified in Drosophila, and several of these are known to regulate growth, metabolism, reproduction, stress responses, and lifespan. However, the functional role of DILP1 is far from understood. Previous work has shown that dilp1/DILP1 is transiently expressed mainly during the pupal stage and the first days of adult life. Here, we study the role of dilp1 in the pupa, as well as in the first week of adult life, and make some comparisons to dilp6 that displays a similar pupal expression profile, but is expressed in fat body rather than brain neurosecretory cells. We show that mutation of dilp1 diminishes organismal weight during pupal development, whereas overexpression increases it, similar to dilp6 manipulations. No growth effects of dilp1 or dilp6 manipulations were detected during larval development. We next show that dilp1 and dilp6 increase metabolic rate in the late pupa and promote lipids as the primary source of catabolic energy. Effects of dilp1 manipulations can also be seen in the adult fly. In newly eclosed female flies, survival during starvation is strongly diminished in dilp1 mutants, but not in dilp2 and dilp1/dilp2 mutants, whereas in older flies, only the double mutants display reduced starvation resistance. Starvation resistance is not affected in male dilp1 mutant flies, suggesting a sex dimorphism in dilp1 function. Overexpression of dilp1 also decreases survival during starvation in female flies and increases egg laying and decreases egg to pupal viability. In conclusion, dilp1 and dilp6 overexpression promotes metabolism and growth of adult tissues during the pupal stage, likely by utilization of stored lipids. Some of the effects of the dilp1 manipulations may carry over from the pupa to affect physiology in young adults, but our data also suggest that dilp1 signaling is important in metabolism and stress resistance in the adult stage.

Integration of some biopesticides against potato tuber moth, Phthorimaea operculella (Zell.), during storage with reference to histopathological changes detected by a transmission electron microscope in the endocrine system

Integration of some biopesticides against potato tuber moth, Phthorimaea operculella (Zell.), during storage with reference to histopathological changes detected by a transmission electron microscope in the endocrine system

Blood feeding activates the vitellogenic stage of oogenesis in the mosquito Aedes aegypti through inhibition of glycogen synthase kinase 3 by the insulin and TOR pathways

Most mosquitoes, including Aedes aegypti, only produce eggs after blood feeding on a vertebrate host. Oogenesis in A. aegypti consists of a pre-vitellogenic stage before blood feeding and a vitellogenic stage after blood feeding. Primary egg chambers remain developmentally arrested during the pre-vitellogenic stage but complete oogenesis to form mature eggs during the vitellogenic stage. In contrast, the signaling factors that maintain primary egg chambers in pre-vitellogenic arrest or that activate vitellogenic growth are largely unclear. Prior studies showed that A. aegypti females release insulin-like peptide 3 (ILP3) and ovary ecdysteroidogenic hormone (OEH) from brain neurosecretory cells after blood feeding. Here, we report that primary egg chambers exit pre-vitellogenic arrest by 8 h post-blood meal as evidenced by proliferation of follicle cells, endoreplication of nurse cells, and formation of cytoophidia. Ex vivo assays showed that ILP3 and OEH stimulate primary egg chambers to exit pre-vitellogenic arrest in the presence of nutrients but not in their absence. Characterization of associated pathways indicated that activation of insulin/insulin growth factor signaling (IIS) by ILP3 or OEH inactivated glycogen synthase kinase 3 (GSK3) via phosphorylation by phosphorylated Akt. GSK3 inactivation correlated with accumulation of the basic helix-loop-helix transcription factor Max and primary egg chambers exiting pre-vitellogenic arrest. Direct inhibition of GSK3 by CHIR-99021 also stimulated Myc/Max accumulation and primary egg chambers exiting pre-vitellogenic arrest. Collectively, our results identify GSK3 as a key factor in regulating the pre- and vitellogenic stages of oogenesis in A. aegypti.

Configuration of nerve cord and characterization of brain neurosecretory cells in adult firefly, Luciola gorhami (Coleoptera: Lampyridae)

Nerve cord configuration and brain neurosecretory cell (NSC) characteristics were studied in adult firefly, Luciola gorhami, applying two methods, in situ and section staining. Nerve cord was of primitive type and consisted of brain, subesophageal ganglion, three thoracic and seven abdominal ganglia which were connected to each other serially through a pair of longitudinal connectives. Thoracic ganglia were separated and had the same size. All abdominal ganglia had the same size except the last one which was twice larger than the others. Abdominal ganglia were not fused with thoracic ganglia. Using in situ staining, 26 neurosecretory cells (NSCs) stained as median neurosecretory cells (MNSCs) and lateral neurosecretory cells (LNSCs). MNSCs consisted of 20 cells in three groups in pars intercerebralis. MNSCs had a U shaped arrangement in such a way that 4 round and large cells were located in front and two parallel groups (8 pryiform to round cells in each group) located in back. LNSCs were comprised of 6 large cells in two groups (one group on each lateral lobe of protocerebrum). MNSCs pathways were not clear but LNSCs pathways were clear and ipsilateral. Using section staining, large number of NSCs in pars intercerebralis stained gray and purple in color. Gray cells were large, more in number and appeared in many sections. Purple cells were large and grouped in the middle of gray cells. Both types of cells were on the surface area of brain and had large nucleus. Their axons were bundled together and extended backwards to the rear of brain.

Insect hormones: more than 50-years after the discovery of insect juvenile hormone analogues (JHA, juvenoids)

Insect hormones: more than 50-years after the discovery of insect juvenile hormone analogues (JHA, juvenoids)

Insulin-like and IGF-like peptides in the silkmoth Bombyx mori: discovery, structure, secretion, and function.

A quarter of a century has passed since bombyxin, the first insulin-like peptide identified in insects, was discovered in the silkmoth Bombyx mori. During these years, bombyxin has been studied for its structure, genes, distribution, hemolymph titers, secretion control, as well as physiological functions, thereby stimulating a wide range of studies on insulin-like peptides in other insects. Moreover, recent studies have identified a new class of insulin family peptides, IGF-like peptides, in B. mori and Drosophila melanogaster, broadening the base of the research area of the insulin-related peptides in insects. In this review, we describe the achievements of the studies on insulin-like and IGF-like peptides mainly in B. mori with short histories of their discovery. Our emphasis is that bombyxins, secreted by the brain neurosecretory cells, regulate nutrient-dependent growth and metabolism, whereas the IGF-like peptides, secreted by the fat body and other peripheral tissues, regulate stage-dependent growth of tissues.

Conserved role for the Dachshund protein with Drosophila Pax6 homolog Eyeless in insulin expression

Members of the insulin family peptides have conserved roles in the regulation of growth and metabolism in a wide variety of metazoans. The Drosophila genome encodes seven insulin-like peptide genes, dilp1-7, and the most prominent dilps (dilp2, dilp3, and dilp5) are expressed in brain neurosecretory cells known as "insulin-producing cells" (IPCs). Although these dilps are expressed in the same cells, the expression of each dilp is regulated independently. However, the molecular mechanisms that regulate the expression of individual dilps in the IPCs remain largely unknown. Here, we show that Dachshund (Dac), which is a highly conserved nuclear protein, is a critical transcription factor that specifically regulates dilp5 expression. Dac was strongly expressed in IPCs throughout development. dac loss-of-function analyses revealed a severely reduced dilp5 expression level in young larvae. Dac interacted physically with the Drosophila Pax6 homolog Eyeless (Ey), and these proteins synergistically promoted dilp5 expression. In addition, the mammalian homolog of Dac, Dach1/2, facilitated the promoting action of Pax6 on the expression of islet hormone genes in cultured mammalian cells. These observations indicate the conserved role of Dac/Dach in controlling insulin expression in conjunction with Ey/Pax6.

MTORC1 inhibition and ECM–cell adhesion-independent drug resistance via PI3K–AKT and PI3K–RAS–MAPK feedback loops

Mammalian target of rapamycin (mTOR) serine threonine kinase is the enzyme that regulates cancer cell growth by altering nutrient supplies to cancer cells. The neuropeptide (proline-rich peptide 1 (PRP-1)), galarmin, produced by the brain neurosecretory cells is a mTOR kinase inhibitor with powerful 80% antiproliferative cytostatic effect in a high-grade chondosarcoma and other mesenchymal tumors. However, the negative feedback loop of phosphatidylinositol 3 kinase-Protein kinase B (PKB), PI3K-AKT and PI3K-rat sarcoma (RAS)-mitogen-activated protein kinase (MAPK) activation is well documented for mTOR inhibitors. This study explored the involvement of those loops in drug resistance after the treatment with mTOR complex 1 (mTORC1) inhibitor, PRP-1. Multidrug resistance assay (MDR) demonstrated that this cytokine did not inhibit permeability glycoprotein-mediated MDR in chondrosarcoma. Phospho-MAPK array in human chondrosarcoma cell line treated with galarmin (10μg/ml,) showed a strong upregulation of phosphorylated glycogen synthase kinase 3β (GSK3β) via activation of PI3K-AKT and MAPK feedback loops. Such GSK3β inactivation leads to β-catenin accumulation that entails drug resistance. The ability of cells to metastasize is reflected in their capacity to adhere to extracellular matrix and endothelium. Laminin cell adhesion assay demonstrated that PRP-1 in the same concentrations that inhibit mTOR kinase inhibited JJ012 chondrosarcoma cell adhesion. The neuropeptide did not have any effect on the expression of total focal adhesion kinase and its phosphorylated form. Thus, it was not accompanied by total HAT downregulation and total HDAC upregulation. Combinatorial treatments of PRP-1 with MAPK and PI3K/AKT inhibitors most probably will lead to full cytotoxicity overcoming drug resistance.

Neuropeptide Y-like signalling and nutritionally mediated gene expression and behaviour in the honey bee

Previous research has led to the idea that derived traits can arise through the evolution of novel roles for conserved genes. We explored whether neuropeptide Y (NPY)-like signalling, a conserved pathway that regulates food-related behaviour, is involved in a derived, nutritionally-related trait, the division of labour in worker honey bees. Transcripts encoding two NPY-like peptides were expressed in separate populations of brain neurosecretory cells, consistent with endocrine functions. NPY-related genes were upregulated in the brains of older foragers compared with younger bees performing brood care ('nurses'). A subset of these changes can be attributed to nutrition, but neuropeptide F peptide treatments did not influence sugar intake. These results contrast with recent reports of more robust associations between division of labour and the related insulin-signalling pathway and suggest that some elements of molecular pathways associated with feeding behaviour may be more evolutionarily labile than others.