Activation of 5-HT(1A) receptors attenuates tachycardia induced by restraint stress in rats

To better understand the central mechanisms that mediate increases in heart rate (HR) during psychological stress, we examined the effects of systemic and intramedullary (raphe region) administration of the serotonin-1A (5-HT(1A)) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) on cardiac changes elicited by restraint in hooded Wistar rats with preimplanted ECG telemetric transmitters. 8-OH-DPAT reduced basal HR from 356 +/- 12 to 284 +/- 12 beats/min, predominantly via a nonadrenergic, noncholinergic mechanism. Restraint stress caused tachycardia (an initial transient increase from 318 +/- 3 to 492 +/- 21 beats/min with a sustained component of 379 +/- 12 beats/min). beta-Adrenoreceptor blockade with atenolol suppressed the sustained component, whereas muscarinic blockade with methylscopolamine (50 microg/kg) abolished the initial transient increase, indicating that sympathetic activation and vagal withdrawal were responsible for the tachycardia. Systemic administration of 8-OH-DPAT (10, 30, and 100 microg/kg) attenuated stress-induced tachycardia in a dose-dependent manner, and this effect was suppressed by the 5-HT(1A) antagonist WAY-100635 (100 microg/kg). Given alone, the antagonist had no effect. Systemically injected 8-OH-DPAT (100 microg/kg) attenuated the sympathetically mediated sustained component (from +85 +/- 19 to +32 +/- 9 beats/min) and the vagally mediated transient (from +62 +/- 5 to +25 +/- 3 beats/min). Activation of 5-HT(1A) receptors in the medullary raphe by microinjection of 8-OH-DPAT mimicked the antitachycardic effect of the systemically administered drug but did not affect basal HR. We conclude that tachycardia induced by restraint stress is due to a sustained increase in cardiac sympathetic activity associated with a transient vagal withdrawal. Activation of central 5-HT(1A) receptors attenuates this tachycardia by suppressing autonomic effects. At least some of the relevant receptors are located in the medullary raphe-parapyramidal area.     

Function and structure of lipid storage droplet protein 1 studied in lipoprotein complexes

Triglycerides (TG) stored in lipid droplets (LDs) are the main energy reserve in all animals. The mechanism by which animals mobilize TG is complex and not fully understood. Several proteins surrounding the LDs have been implicated in TG homeostasis such as mammalian perilipin A and insect lipid storage proteins (Lsd). Most of the knowledge on LD-associated proteins comes from studies using cells or LDs leaving biochemical properties of these proteins uncharacterized. Here we describe the purification of recombinant Lsd1 and its reconstitution with lipids to form lipoprotein complexes suitable for functional and structural studies. Lsd1 in the lipid bound state is a predominately α-helical protein. Using lipoprotein complexes containing triolein it is shown that PKA mediated phosphorylation of Lsd1 promoted a 1.7-fold activation of the main fat body lipase demonstrating the direct link between Lsd1 phosphorylation and activation of lipolysis. Serine 20 was identified as the Lsd1-phosphorylation site triggering this effect.     

Differential responses of male and female red swordtails to chemical alarm cues

Male and female red swordtails Xiphophorus helleri exposed in the laboratory to swordtail skin extract, fathead minnow Pimephales promelas skin extract and distilled water, significantly decreased activity in response to conspecific skin extract compared to minnow skin extract or distilled water. Moreover, males and females responded differentially to conspecific skin extract. Males tended to occupy the top compartment of the tank, whereas females tended to occupy the bottom compartment and seek shelter more. In a second experiment swordtails reduced activity significantly more in response to swordtail skin extract compared to closely related guppy Poecilia reticulata skin extract, minnow skin extract or distilled water. Swordtails also reduced activity significantly more to guppy skin extract compared to minnow skin and distilled water. However, males and females did not respond differentially to guppy skin extract. This suggests that chemical alarm cues are partially conserved within the Poeciliidae, but the level of response is of lower intensity to heterospecific skin extracts.     

A statistical approach for detecting genomic aberrations in heterogeneous tumor samples from single nucleotide polymorphism genotyping data

We describe a statistical method for the characterization of genomic aberrations in single nucleotide polymorphism microarray data acquired from cancer genomes. Our approach allows us to model the joint effect of polyploidy, normal DNA contamination and intra-tumour heterogeneity within a single unified Bayesian framework. We demonstrate the efficacy of our method on numerous datasets including laboratory generated mixtures of normal-cancer cell lines and real primary tumours.     

Hydroxysteroid dehydrogenase family proteins on lipid droplets through bacteria, C. elegans, and mammals

Lipid droplets (LDs) are the main fat storing sites in almost all species from bacteria to humans. The perilipin family has been found as LD proteins in mammals, Drosophila, and a couple of slime molds, but no bacterial LD proteins containing sequence conservation were identified. In this study, we reported that the hydroxysteroid dehydrogenase (HSD) family was found on LDs across all organisms by LD proteomic analysis. Imaging experiments confirmed LD targeting of three representative HSD proteins including ro01416 in RHA1, DHS-3 in C. elegans, and 17β-HSD11 in human cells. In C. elegans, 17β-HSD11 family proteins (DHS-3, DHS-4 and DHS-19) were localized on LDs in distinct tissues. In intestinal cells of C. elegans, DHS-3 targeted to cytoplasmic LDs, while DHS-9 labeled nuclear LDs. Furthermore, the N-terminal hydrophobic domains of 17β-HSD11 family were necessary for their targeting to LDs. Last, 17β-HSD11 family proteins induced LD aggregation, and deletion of DHS-3 in C. elegans caused lipid decrease. Independent of their presumptive catalytic sites, 17β-HSD11 family proteins regulated LD dynamics and lipid metabolism through affecting the LD-associated ATGL, which was conserved between C. elegans and humans. Together, these findings for HSDs provide a new insight not only into the mechanistic studies of the dynamics and functions of LDs in multiple organisms, but also into understanding the evolutionary history of the organelle.     

Webbing life type and behavioral response of the date palm mite, <Emphasis Type="Italic">Oligonychus afrasiaticus</Emphasis>, to webbing residues on leaves and fruits of date palm

The present study examined the webbing life type and behavioral response of date palm mite (DPM) Oligonychus afrasiaticus (McGregor) toward its webbing residues, in presence or absence of immature individuals, on leaves and fruits of date palm. DPM exhibited a complicated web life type on both the leaves and fruits of date palm, which is characterized by the following features: complicated irregular web structure; webbing density on the leaves is medium and on the fruits extremely high; eggs are always laid on the threads of web without web cover; fecal pellets are deposited on the substrate surface (both leaf and fruit); quiescent stages are on the silken web threads; and the preferred site for feeding and walking is under the web. Behavioral observation of DPM females revealed that the midrib of leaves and the base of fruits of date palm were the preferred sites for feeding and web construction. The number and development stage of DPM affected the behavioral response of females on date palm leaves but not on the fruits. DPM spent most time feeding under the web on both the leaves and fruits of date palm.     

P2RY1/ALK3-Expressing Cells within the Adult Human Exocrine Pancreas Are BMP-7 Expandable and Exhibit Progenitor-like Characteristics

1. Download high-res image (223KB)
2. Download full-size image