Investigating postsynaptic effects of a Drosophila neuropeptide on muscle contraction.

The Drosophila neuropeptide, DPKQDFMRFamide, was previously shown to enhance excitatory junctional potentials (EJPs) and muscle contraction by both presynaptic and postsynaptic actions. Since the peptide acts on both sides of the synaptic cleft, it has been difficult to examine postsynaptic modulatory mechanisms, particularly when contractions are elicited by nerve stimulation. Here, postsynaptic actions are examined in 3rd instar larvae by applying peptide and the excitatory neurotransmitter, l-glutamate, in the bathing solution to elicit contractions after silencing motor output by removing the central nervous system (CNS). DPKQDFMRFamide enhanced glutamate-evoked contractions at low concentrations (EC50 1.3 nM), consistent with its role as a neurohormone, and the combined effect of both substances was supra-additive. Glutamate-evoked contractions were also enhanced when transmitter release was blocked in temperature-sensitive (Shibire) mutants, confirming the peptide's postsynaptic action. The peptide increased membrane depolarization in muscle when co-applied with glutamate, and its effects were blocked by nifedipine, an L-type channel blocker, indicating effects at the plasma membrane involving calcium influx. DPKQDFMRFamide also enhanced contractions induced by caffeine in the absence of extracellular calcium, suggesting increased calcium release from the sarcoplasmic reticulum (SR) or effects downstream of calcium release from the SR. The peptide's effects do not appear to involve calcium/calmodulin-dependent protein kinase II (CaMKII), previously shown to mediate presynaptic effects. The approach used here might be useful for examining postsynaptic effects of neurohormones and cotransmitters in other systems.NEW & NOTEWORTHY Distinguishing presynaptic and postsynaptic effects of neurohormones is a long-standing challenge in many model organisms. Here, postsynaptic actions of DPKQDFMRFamide are demonstrated by assessing its ability to potentiate contractions elicited by direct application of the neurotransmitter, glutamate, when axons are silent and when transmitter release is blocked. The peptide acts at multiple sites to increase contraction, increasing glutamate-induced depolarization at the cell membrane, acting on L-type channels, and acting downstream of calcium release from the sarcoplasmic reticulum.

Leucokinins: Multifunctional Neuropeptides and Hormones in Insects and Other Invertebrates.

Leucokinins (LKs) constitute a neuropeptide family first discovered in a cockroach and later identified in numerous insects and several other invertebrates. The LK receptors are only distantly related to other known receptors. Among insects, there are many examples of species where genes encoding LKs and their receptors are absent. Furthermore, genomics has revealed that LK signaling is lacking in several of the invertebrate phyla and in vertebrates. In insects, the number and complexity of LK-expressing neurons vary, from the simple pattern in the Drosophila larva where the entire CNS has 20 neurons of 3 main types, to cockroaches with about 250 neurons of many different types. Common to all studied insects is the presence or 1-3 pairs of LK-expressing neurosecretory cells in each abdominal neuromere of the ventral nerve cord, that, at least in some insects, regulate secretion in Malpighian tubules. This review summarizes the diverse functional roles of LK signaling in insects, as well as other arthropods and mollusks. These functions include regulation of ion and water homeostasis, feeding, sleep-metabolism interactions, state-dependent memory formation, as well as modulation of gustatory sensitivity and nociception. Other functions are implied by the neuronal distribution of LK, but remain to be investigated.

The effects of melatonin on neurohormonal regulation in cardiac cachexia: A mechanistic review.

Heart failure (HF) is one of the prominent health concerns and its morbidity is comparable to many malignancies. Cardiac cachexia (CC), characterized by significant weight loss and muscle wasting, frequently occurs in progressive stage of HF. The pathophysiology of CC is multifactorial including nutritional and gastrointestinal alterations, immunological and neurohormonal activation, and anabolic/catabolic imbalance. Neurohormones are critically involved in the development of both HF and CC. Melatonin is known as an anti-inflammatory and antioxidant hormone. It seems that melatonin possibly regulates the neurohormonal signaling pathway related to muscle wasting in CC, but limited comprehensive data is available on the mechanistic aspects of its activity. In this, we reviewed the reports regarding the role of neurohormones in CC occurrence and possible activity of melatonin in modulation of HF and subsequently CC via neurohormonal regulation. In addition, we have discussed proposed mechanisms of action for melatonin considering its possible interactions with neurohormones. In conclusion, melatonin likely regulates the signaling pathways related to muscle wasting in CC by reducing tumor necrosis factor α levels and activating the gene expression of insulin-like growth factor-1. Also, this hormone inhibits the proteolytic pathway by inhibiting nuclear factor-κB (NF-κB), renin-angiotensin system and forkhead box protein O1 pathways and could increase protein synthesis by activating Akt and mammalian target of rapamycin. To elucidate the positive role of melatonin in CC and exact mechanisms related to muscle wasting more cellular and clinical trial studies are needed.

AMGSEFLamide, a member of a broadly conserved peptide family, modulates multiple neural networks in Homarus americanus.

Recent genomic/transcriptomic studies have identified a novel peptide family whose members share the carboxyl terminal sequence -GSEFLamide. However, the presence/identity of the predicted isoforms of this peptide group have yet to be confirmed biochemically, and no physiological function has yet been ascribed to any member of this peptide family. To determine the extent to which GSEFLamides are conserved within the Arthropoda, we searched publicly accessible databases for genomic/transcriptomic evidence of their presence. GSEFLamides appear to be highly conserved within the Arthropoda, with the possible exception of the Insecta, in which sequence evidence was limited to the more basal orders. One crustacean in which GSEFLamides have been predicted using transcriptomics is the lobster, Homarus americanus Expression of the previously published transcriptome-derived sequences was confirmed by reverse transcription (RT)-PCR of brain and eyestalk ganglia cDNAs; mass spectral analyses confirmed the presence of all six of the predicted GSEFLamide isoforms - IGSEFLamide, MGSEFLamide, AMGSEFLamide, VMGSEFLamide, ALGSEFLamide and AVGSEFLamide - in H. americanus brain extracts. AMGSEFLamide, of which there are multiple copies in the cloned transcripts, was the most abundant isoform detected in the brain. Because the GSEFLamides are present in the lobster nervous system, we hypothesized that they might function as neuromodulators, as is common for neuropeptides. We thus asked whether AMGSEFLamide modulates the rhythmic outputs of the cardiac ganglion and the stomatogastric ganglion. Physiological recordings showed that AMGSEFLamide potently modulates the motor patterns produced by both ganglia, suggesting that the GSEFLamides may serve as important and conserved modulators of rhythmic motor activity in arthropods.

Predatory behavior changes with satiety or increased insulin levels in the praying mantis (Tenodera sinensis).

At any given moment, behavior is controlled by a combination of external stimuli and an animal's internal state. As physiological conditions change, vastly different behaviors might result from the same stimuli. For example, the motivation to hunt and hunting strategy are influenced by satiety. Here, we describe how sensory responsiveness and motor activity of a praying mantis (Tenodera sinensis) change as the insect feeds, leading to an altered hunting strategy. We further show that these changes can be induced by injection of insulin, which likely functions as a metabotropic indicator. Praying mantises directed their attention toward real and simulated prey less often as they fed and became sated. The range of distance and azimuth at which prey was detected decreased as did pursuit of prey, while opportunistic close-range attacks persisted. Together, these sensorimotor changes are indicative of a behavioral paradigm shift from 'pursuit' to 'ambush'. A similar effect was induced in starved praying mantises injected with 0.05 ml of 200 µg ml-1 bovine insulin. These experiments showed that insulin injection into the circulating hemolymph is sufficient to decrease prey orientation as well as in prey-directed locomotor behaviors (tracking and pursuit). The effects of prey consumption and insulin injection were similarly dose dependent. These results suggest that insulin is a signal of internal, physiological conditions that can modify responses to external stimuli. A change in hunting strategy thus results from coordinated effects of a neurohormone on a set of independent sensorimotor processes and the overall activity level of the animal.

Three members of a peptide family are differentially distributed and elicit differential state-dependent responses in a pattern generator-effector system.

C-type allatostatins (AST-Cs) are pleiotropic neuropeptides that are broadly conserved within arthropods; the presence of three AST-C isoforms, encoded by paralog genes, is common. However, these peptides are hypothesized to act through a single receptor, thereby exerting similar bioactivities within each species. We investigated this hypothesis in the American lobster, Homarus americanus, mapping the distributions of AST-C isoforms within relevant regions of the nervous system and digestive tract, and comparing their modulatory influences on the cardiac neuromuscular system. Immunohistochemistry showed that in the pericardial organ, a neuroendocrine release site, AST-C I and/or III and AST-C II are contained within distinct populations of release terminals. Moreover, AST-C I/III-like immunoreactivity was seen in midgut epithelial endocrine cells and the cardiac ganglion (CG), whereas AST-C II-like immunoreactivity was not seen in these tissues. These data suggest that AST-C I and/or III can modulate the CG both locally and hormonally; AST-C II likely acts on the CG solely as a hormonal modulator. Physiological studies demonstrated that all three AST-C isoforms can exert differential effects, including both increases and decreases, on contraction amplitude and frequency when perfused through the heart. However, in contrast to many state-dependent modulatory changes, the changes in contraction amplitude and frequency elicited by the AST-Cs were not functions of the baseline parameters. The responses to AST-C I and III, neither of which is COOH-terminally amidated, are more similar to one another than they are to the responses elicited by AST-C II, which is COOH-terminally amidated. These results suggest that the three AST-C isoforms are differentially distributed in the lobster nervous system/midgut and can elicit distinct behaviors from the cardiac neuromuscular system, with particular structural features, e.g., COOH-terminal amidation, likely important in determining the effects of the peptides. NEW & NOTEWORTHY Multiple isoforms of many peptides exert similar effects on neural circuits. In this study we show that each of the three isoforms of C-type allatostatin (AST-C) can exert differential effects, including both increases and decreases in contraction amplitude and frequency, on the lobster cardiac neuromuscular system. The distribution of effects elicited by the nonamidated isoforms AST-C I and III are more similar to one another than to the effects of the amidated AST-C II.

Bacterial and fungal infections induce bursts of dopamine in the haemolymph of the Colorado potato beetle Leptinotarsa decemlineata and greater wax moth Galleria mellonella.

Dopamine (DA) is known as a hormone neurotrasnmitter molecule involved in several stress reactions in both vertebrates and invertebrates. Following infections with the fungi Metarhizium robertsii or Beauveria bassiana and the bacterium Bacillus thuringiensis, dopamine the concentration was measured at different time points in the haemolymph of the Colorado potato beetle, Leptinotarsa decemlineata and the larvae of the greater wax moth Galleria mellonella. The infection with M. robertsii increased (4 to 12-fold) DA concentrations in the haemolymph of the potato beetle larvae and the oral infection by B. thuringiensis also lead to a 30 and 45-fold increase. During infection of the greater wax moth larvae with Beauveria bassiana and B. thuringiensis DA increased 4 to 20-fold and about 2 to 2,5-fold respectively, compared to non-infected insects. The relative DA concentrations varied between the two insects and depended on the pathogens and post infection time.

Neurohormone levels remain elevated in continuous flow left ventricular assist device recipients.

INTRODUCTION: The levels of neurohormones were assessed in continuous-flow left ventricular assist device (CF-LVAD) recipients and compared to patients with heart failure (HF) and to healthy controls (HCs), and CF-LVAD recipients with closed or open aortic valves (AVs). METHODS: Aldosterone, norepinephrine, and renin levels were assessed in a total of 46 participants, including CF-LVAD recipients (n = 18), HF patients (n = 14), and HC individuals (n = 14). Echocardiographic assessments were performed to evaluate cardiac functions and aortic valve status and neurohormone levels were compared between CF-LVAD recipients with closed or open AVs. RESULTS: Aldosterone, norepinephrine, and renin levels were elevated to a similar extent in CF-LVAD recipients and HF patients, compared to HC individuals. In the CF-LVAD group, no differences were found between the levels of norepinephrine and aldosterone between recipients with AV opened or closed. With an open AVs, CF-LVAD recipients had higher levels of renin compared to recipients with closed AVs. However, an open AV was only a weak predictor of higher levels of renin. CONCLUSION: The findings that aldosterone, norepinephrine, and renin were elevated after restoration of hemodynamic functions during LVAD support suggest that the levels of neurohormones did not normalize. Future studies should investigate whether AV status in CF-LVAD recipients affects the levels of RAAS neurohormones and the mechanisms and clinical implications of elevated levels of neurohormones in CF-LVAD patients.

The association of heart failure-related microRNAs with neurohormonal signaling.

Heart failure (HF) is a widely prevalent syndrome imposing a significant burden of morbidity and mortality world-wide. Differential circulating microRNA profiles observed in HF cohorts suggest the diagnostic utility of microRNAs as biomarkers. Given their function in fine tuning gene expression, alternations in microRNA landscape could reflecting the underlying mechanisms of disease and present potential therapeutic targets. Using multiple computational target predicting algorithms together with the luciferase-based reporting platform, the interactions between HF-related microRNAs and the 3' untranslated regions (3'UTRs) of neurohormone associated genes were examined and compared. Our results indicate that although in silico prediction provides an overview of possible microRNA-mRNA target pairs, less than half of the predicted interactions were experimentally confirmed by reporter assays in HeLa cells. Thus, the establishment of microRNA/3'UTR reporters is essential to systemically evaluate the roles of microRNAs for signaling cascades of interest, including cardiovascular neurohormonal signaling. The physiological relevance of HF-related microRNAs on the expression of putative gene targets was further established by using gain-of-function assays in two human cardiac-derived cells. Our findings, for the first time, provide direct evidence of the regulatory effects of HF-related microRNAs on the neurohormonal signaling in cardiac cells. More importantly, our study presents a rational approach to further exploring microRNA profiling data in deciphering the role of microRNA in complex syndromes such as HF. This article is part of a Special Issue entitled: Genetic and epigenetic control of heart failure - edited by Jun Ren & Megan Yingmei Zhang.

Prediction of a peptidome for the western tarnished plant bug Lygus hesperus.

Many strategies for controlling insect pests require an understanding of their hormonal signaling agents, peptides being the largest and most diverse single class of these molecules. Lygus hesperus is a pest species of particular concern, as it is responsible for significant damage to a wide variety of commercially important plant crops. At present, little is known about the peptide hormones of L. hesperus. Here, transcriptomic data were used to predict a peptidome for L. hesperus. Fifty-three L. hesperus transcripts encoding peptide precursors were identified, with a subset amplified by PCR for sequence verification. The proteins deduced from these transcripts allowed for the prediction of a 119-sequence peptidome for L. hesperus. The predicted peptides include isoforms of allatostatin A, allatostatin B (AST-B), allatostatin C, allatotropin, bursicon, CCHamide, corazonin, crustacean cardioactive peptide, crustacean hyperglycemic hormone/ion transport peptide, diuretic hormone 31, GSEFLamide, insulin-like peptide, myosuppressin, neuroparsin, neuropeptide F, orcokinin, orcomyotropin, pyrokinin, short neuropeptide F, SIFamide, sulfakinin and tachykinin-related peptide. Of note were several isoforms of AST-B that possess -WX7Wamide carboxyl-termini rather than the stereotypical -WX6Wamide (e.g., KWQDMQNPGWamide), an allatotropin ending in -SARGFamide rather than -TARGFamide (GLKNGPLNSARGFamide), a GSEFLamide ending in -GTEFLamide (TVGTEFLamide), several orcokinins with PMDEIDR- rather than NFDEIDR- amino-termini (e.g., PMDEIDRAGFTHFV), and an eight rather than 12 amino acid long isoform of SIFamide (PPFNGSIFamide). Collectively, the L. hesperus peptidome predicted here provides a resource for initiating physiological investigations of peptidergic signaling in this species, including studies directed at the biological control of this agricultural pest.

Prediction of a neuropeptidome for the eyestalk ganglia of the lobster Homarus americanus using a tissue-specific de novo assembled transcriptome.

In silico transcriptome mining is a powerful tool for crustacean peptidome prediction. Using homology-based BLAST searches and a simple bioinformatics workflow, large peptidomes have recently been predicted for a variety of crustaceans, including the lobster, Homarus americanus. Interestingly, no in silico studies have been conducted on the eyestalk ganglia (lamina ganglionaris, medulla externa, medulla interna and medulla terminalis) of the lobster, although the eyestalk is the location of a major neuroendocrine complex, i.e., the X-organ-sinus gland system. Here, an H. americanus eyestalk ganglia-specific transcriptome was produced using the de novo assembler Trinity. This transcriptome was generated from 130,973,220 Illumina reads and consists of 147,542 unique contigs. Eighty-nine neuropeptide-encoding transcripts were identified from this dataset, allowing for the deduction of 62 distinct pre/preprohormones. Two hundred sixty-two neuropeptides were predicted from this set of precursors; the peptides include members of the adipokinetic hormone-corazonin-like peptide, allatostatin A, allatostatin B, allatostatin C, bursicon α, CCHamide, corazonin, crustacean cardioactive peptide, crustacean hyperglycemic hormone (CHH), CHH precursor-related peptide, diuretic hormone 31, diuretic hormone 44, eclosion hormone, elevenin, FMRFamide-like peptide, glycoprotein hormone α2, glycoprotein hormone ß5, GSEFLamide, intocin, leucokinin, molt-inhibiting hormone, myosuppressin, neuroparsin, neuropeptide F, orcokinin, orcomyotropin, pigment dispersing hormone, proctolin, pyrokinin, red pigment concentrating hormone, RYamide, short neuropeptide F, SIFamide, sulfakinin, tachykinin-related peptide and trissin families. The predicted peptides expand the H. americanus eyestalk ganglia neuropeptidome approximately 7-fold, and include 78 peptides new to the lobster. The transcriptome and predicted neuropeptidome described here provide new resources for investigating peptidergic signaling within/from the lobster eyestalk ganglia.

Preclinical efficacy of growth hormone-releasing hormone antagonists for androgen-dependent and castration-resistant human prostate cancer.

Advanced hormone-sensitive prostate cancer responds to androgen-deprivation therapy (ADT); however, therapeutic options for recurrent castration-resistant disease are limited. Because growth hormone-releasing hormone (GHRH) and GHRH receptor (GHRH-R) are regulated in an autocrine fashion in prostate cancer, inhibition of GHRH-R represents a compelling approach to treatment. We investigated the effects of the latest series of improved, highly potent GHRH antagonists--MIA-602, MIA-606, and MIA-690--on the growth of androgen-dependent as well as castration-resistant prostate cancer (CRPC) cells in vitro and in vivo. GHRH-R and its splice variant, SV1, were present in 22Rv1, LNCaP, and VCaP human prostate cancer cell lines. Androgen-dependent LNCaP and VCaP cells expressed higher levels of GHRH-R protein compared with castration-resistant 22Rv1 cells; however, 22Rv1 expressed higher levels of SV1. In vitro, MIA-602 decreased cell proliferation of 22Rv1, LNCaP, and VCaP prostate cancer cell lines by 70%, 61%, and 20%, respectively (all P < 0.05), indicating direct effects of MIA-602. In vivo, MIA-602 was more effective than MIA-606 and MIA-690 and decreased 22Rv1 xenograft tumor volumes in mice by 63% after 3 wk (P < 0.05). No noticeable untoward effects or changes in body weight occurred. In vitro, the VCaP cell line was minimally inhibited by MIA-602, but in vivo, this line showed a substantial reduction in growth of xenografts in response to MIA-602, indicating both direct and systemic inhibitory effects. MIA-602 also further inhibited VCaP xenografts when combined with ADT. This study demonstrates the preclinical efficacy of the GHRH antagonist MIA-602 for treatment of both androgen-dependent and CRPC.

Prediction of Scylla olivacea (Crustacea; Brachyura) peptide hormones using publicly accessible transcriptome shotgun assembly (TSA) sequences.

The aquaculture of crabs from the genus Scylla is of increasing economic importance for many Southeast Asian countries. Expansion of Scylla farming has led to increased efforts to understand the physiology and behavior of these crabs, and as such, there are growing molecular resources for them. Here, publicly accessible Scylla olivacea transcriptomic data were mined for putative peptide-encoding transcripts; the proteins deduced from the identified sequences were then used to predict the structures of mature peptide hormones. Forty-nine pre/preprohormone-encoding transcripts were identified, allowing for the prediction of 187 distinct mature peptides. The identified peptides included isoforms of adipokinetic hormone-corazonin-like peptide, allatostatin A, allatostatin B, allatostatin C, bursicon ß, CCHamide, corazonin, crustacean cardioactive peptide, crustacean hyperglycemic hormone/molt-inhibiting hormone, diuretic hormone 31, eclosion hormone, FMRFamide-like peptide, HIGSLYRamide, insulin-like peptide, intocin, leucokinin, myosuppressin, neuroparsin, neuropeptide F, orcokinin, pigment dispersing hormone, pyrokinin, red pigment concentrating hormone, RYamide, short neuropeptide F, SIFamide and tachykinin-related peptide, all well-known neuropeptide families. Surprisingly, the tissue used to generate the transcriptome mined here is reported to be testis. Whether or not the testis samples had neural contamination is unknown. However, if the peptides are truly produced by this reproductive organ, it could have far reaching consequences for the study of crustacean endocrinology, particularly in the area of reproductive control. Regardless, this peptidome is the largest thus far predicted for any brachyuran (true crab) species, and will serve as a foundation for future studies of peptidergic control in members of the commercially important genus Scylla.

Expansion of the neuropeptidome of the globally invasive marine crab Carcinus maenas.

Carcinus maenas is widely recognized as one of the world's most successful marine invasive species; its success as an invader is due largely to its ability to thrive under varied environmental conditions. The physiological/behavioral control systems that allow C. maenas to adapt to new environments are undoubtedly under hormonal control, the largest single class of hormones being peptides. While numerous studies have focused on identifying native C. maenas peptides, none has taken advantage of mining transcriptome shotgun assembly (TSA) sequence data, a strategy proven highly successful for peptide discovery in other crustaceans. Here, a C. maenas peptidome was predicted via in silico transcriptome mining. Thirty-seven peptide families were searched for in the extant TSA database, with transcripts encoding precursors for 29 groups identified. The pre/preprohormones deduced from the identified sequences allowed for the prediction of 263 distinct mature peptides, 193 of which are new discoveries for C. maenas. The predicted peptides include isoforms of adipokinetic hormone-corazonin-like peptide, allatostatin A, allatostatin B, allatostatin C, bursicon, CCHamide, corazonin, crustacean cardioactive peptide, crustacean hyperglycemic hormone, diuretic hormone 31, diuretic hormone 44, eclosion hormone, FMRFamide-like peptide, HIGSLYRamide, intocin, leucokinin, myosuppressin, neuroparsin, neuropeptide F, orcokinin, pigment dispersing hormone, proctolin, pyrokinin, red pigment concentrating hormone, RYamide, short neuropeptide F, SIFamide, and tachykinin-related peptide. This peptidome is the largest predicted from any single crustacean using the in silico approach, and provides a platform for investigating peptidergic signaling in C. maenas, including control of the processes that allow for its success as a global marine invader.

Peptidergic signaling in the crab Cancer borealis: Tapping the power of transcriptomics for neuropeptidome expansion.

The crab Cancer borealis has long been used as a model for understanding neural control of rhythmic behavior. One significant discovery made through its use is that even numerically simple neural circuits are capable of producing an essentially infinite array of distinct motor outputs via the actions of locally released and circulating neuromodulators, the largest class being peptides. While much work has focused on elucidating the peptidome of C. borealis, no investigation has used in silico transcriptome mining for peptide discovery in this species, a strategy proven highly effective for identifying neuropeptides in other crustaceans. Here, we mined a C. borealis neural transcriptome for putative peptide-encoding transcripts, and predicted 200 distinct mature neuropeptides from the proteins deduced from these sequences. The identified peptides include isoforms of allatostatin A, allatostatin B, allatostatin C, CCHamide, crustacean cardioactive peptide, crustacean hyperglycemic hormone, diuretic hormone 31 (DH31), diuretic hormone 44 (DH44), FMRFamide-like peptide, GSEFLamide, HIGSLYRamide, insulin-like peptide (ILP), intocin, leucokinin, neuroparsin, pigment dispersing hormone, pyrokinin, red pigment concentrating hormone, short neuropeptide F and SIFamide. While some of the predicted peptides were known previously from C. borealis, most (159) are new discoveries for the species, e.g., the isoforms of CCHamide, DH31, DH44, GSEFLamide, ILP, intocin and neuroparsin, which are the first members of these peptide families identified from C. borealis. Collectively, the peptides predicted here approximately double the peptidome known for C. borealis, and in so doing provide an expanded platform from which to launch new investigations of peptidergic neuromodulation in this species.

Developmental and hormone-induced changes of mitochondrial electron transport chain enzyme activities during the last instar larval development of maize stem borer, Chilo partellus (Lepidoptera: Crambidae).

The energy demand for structural remodelling in holometabolous insects is met by cellular mitochondria. Developmental and hormone-induced changes in the mitochondrial respiratory activity during insect metamorphosis are not well documented. The present study investigates activities of enzymes of mitochondrial electron transport chain (ETC) namely, NADH:ubiquinone oxidoreductase or complex I, Succinate: ubiquinone oxidoreductase or complex II, Ubiquinol:ferricytochrome c oxidoreductase or complex III, cytochrome c oxidase or complex IV and F1F0ATPase (ATPase), during Chilo partellus development. Further, the effect of juvenile hormone (JH) analog, methoprene, and brain and corpora-allata-corpora-cardiaca (CC-CA) homogenates that represent neurohormones, on the ETC enzyme activities was monitored. The enzymatic activities increased from penultimate to last larval stage and thereafter declined during pupal development with an exception of ATPase which showed high enzyme activity during last larval and pupal stages compared to the penultimate stage. JH analog, methoprene differentially modulated ETC enzyme activities. It stimulated complex I and IV enzyme activities, but did not alter the activities of complex II, III and ATPase. On the other hand, brain homogenate declined the ATPase activity while the injected CC-CA homogenate stimulated complex I and IV enzyme activities. Cumulatively, the present study is the first to show that mitochondrial ETC enzyme system is under hormone control, particularly of JH and neurohormones during insect development.

MicroRNA and Heart Failure.

Heart failure (HF) imposes significant economic and public health burdens upon modern society. It is known that disturbances in neurohormonal status play an important role in the pathogenesis of HF. Therapeutics that antagonize selected neurohormonal pathways, specifically the renin-angiotensin-aldosterone and sympathetic nervous systems, have significantly improved patient outcomes in HF. Nevertheless, mortality remains high with about 50% of HF patients dying within five years of diagnosis thus mandating ongoing efforts to improve HF management. The discovery of short noncoding microRNAs (miRNAs) and our increasing understanding of their functions, has presented potential therapeutic applications in complex diseases, including HF. Results from several genome-wide miRNA studies have identified miRNAs differentially expressed in HF cohorts suggesting their possible involvement in the pathogenesis of HF and their potential as both biomarkers and as therapeutic targets. Unravelling the functional relevance of miRNAs within pathogenic pathways is a major challenge in cardiovascular research. In this article, we provide an overview of the role of miRNAs in the cardiovascular system. We highlight several HF-related miRNAs reported from selected cohorts and review their putative roles in neurohormonal signaling.

The Emerging Potential of the Apelin-APJ System in Heart Failure.

The apelin-APJ system is a novel neurohormonal pathway, with studies to date suggesting that it may be of pathophysiologic relevance in heart failure and may indeed be a viable therapeutic target in this syndrome. This interest is driven primarily by the demonstration of its vasodilator, inotropic, and aquaretic actions as well as its apparent antagonistic relationship with the renin-angiotensin system. However, its promise is heightened further by the observation that, unlike other and more established cardioprotective pathways, it appears to be down-regulated in heart failure, suggesting that augmentation of this axis may have a powerful effect on the heart failure syndrome. We review the literature regarding the apelin-APJ system in heart failure and suggest areas requiring further research.

Neuropeptide discovery in the Araneae (Arthropoda, Chelicerata, Arachnida): elucidation of true spider peptidomes using that of the Western black widow as a reference.

The public deposition of large transcriptome shotgun assembly (TSA) datasets for the Araneae (true spiders) provides a resource for determining the structures of the native neuropeptides present in members of this chelicerate order. Here, the Araneae TSA data were mined for putative peptide-encoding transcripts using the recently deduced neuropeptide precursors from the Western black widow Latrodectus hesperus as query templates. Neuropeptide-encoding transcripts from five spiders, Latrodectus tredecimguttatus, Stegodyphus mimosarum, Stegodyphus lineatus, Stegodyphus tentoriicola and Acanthoscurria geniculata, were identified, including ones encoding members of the allatostatin A, allatostatin B, allatostatin C, allatotropin, CAPA/periviscerokinin/pyrokinin, crustacean cardioactive peptide, crustacean hyperglycemic hormone/ion transport peptide, diuretic hormone 31, diuretic hormone 44, eclosion hormone, FMRFamide-like peptide (FLP), GSEFLamide, insulin-like peptide, orcokinin, proctolin, short neuropeptide F, SIFamide, sulfakinin and tachykinin-related peptide (TRP) families. A total of 156 distinct peptides were predicted from the precursor proteins deduced from the S. mimosarum transcripts, with 65, 26, 21 and 12 peptides predicted from those deduced from the A. geniculata, L. tredecimguttatus, S. lineatus and S. tentoriicola sequences, respectively. Among the peptides identified were variant isoforms of FLP, orcokinin and TRP, peptides whose structures are similar to ones previously identified from L. hesperus. The prediction of these atypical peptides from multiple spiders suggests that they may be broadly conserved within the Araneae rather than being species-specific variants. Taken collectively, the data described here greatly expand the number of known Araneae neuropeptides, providing a foundation for future functional studies of peptidergic signaling in this important Chelicerate order.

Neuropeptide discovery in Eucyclops serrulatus (Crustacea, Copepoda): in silico prediction of the first peptidome for a member of the Cyclopoida.

Crustaceans of the subclass Copepoda are key components of essentially all aquatic ecosystems as they serve both as the primary consumers of phytoplankton and/or as major food sources for a wide variety of higher-level consumers. The dominant group of copepods in most freshwater ecosystems is the Cyclopoida; members of this order are routinely used as environmental indicators, and some predatory species are used for the biological control of disease-causing mosquitoes. Given their ecological and disease control importance, it is surprising that little is known about endocrine control in cyclopoids. Here, as part of an ongoing effort to identify and characterize the neurochemical signaling systems of members of the Copepoda, the extant transcriptome shotgun assembly for Eucyclops serrulatus, a member of the Cyclopoida, was mined for transcripts encoding putative peptide hormone-encoding transcripts. Via queries using known arthropod pre/preprohormone sequences, primarily ones from other copepod species, 36 E. serrulatus peptide-encoding transcripts were identified. The proteins deduced from these sequences allowed for the prediction of 160 unique mature neuropeptides, including the first copepod isoform of pigment dispersing hormone, as well as isoforms of adipokinetic hormone-corazonin-like peptide, allatostatin A, allatostatin B, allatostatin C, allatotropin, crustacean hyperglycemic hormone, diuretic hormone 31, DXXRLamide, FLRFamide, FXGGXamide, GSEFLamide, insulin-like peptide, intocin, leucokinin, myosuppressin, neuroparsin, neuropeptide F and tachykinin-related peptide. These peptides are currently the only ones known from any member of the Cyclopoida, and as such, provide a new resource for investigating peptidergic signaling in this important copepod order.