The melanin-concentrating hormone (MCH) system modulates behaviors associated with psychiatric disorders

Deficits in sensorimotor gating measured by prepulse inhibition (PPI) of the startle have been known as characteristics of patients with schizophrenia and related neuropsychiatric disorders. PPI disruption is thought to rely on the activity of the mesocorticolimbic dopaminergic system and is inhibited by most antipsychotic drugs. These drugs however act also at the nigrostriatal dopaminergic pathway and exert adverse locomotor responses. Finding a way to inhibit the mesocorticolimbic- without affecting the nigrostriatal-dopaminergic pathway may thus be beneficial to antipsychotic therapies. The melanin-concentrating hormone (MCH) system has been shown to modulate dopamine-related responses. Its receptor (MCH1R) is expressed at high levels in the mesocorticolimbic and not in the nigrostriatal dopaminergic pathways. Interestingly a genomic linkage study revealed significant associations between schizophrenia and markers located in the MCH1R gene locus. We hypothesize that the MCH system can selectively modulate the behavior associated with the mesocorticolimbic dopamine pathway. Using mice, we found that central administration of MCH potentiates apomorphine-induced PPI deficits. Using congenic rat lines that differ in their responses to PPI, we found that the rats that are susceptible to apomorphine (APO-SUS rats) and exhibit PPI deficits display higher MCH mRNA expression in the lateral hypothalamic region and that blocking the MCH system reverses their PPI deficits. On the other hand, in mice and rats, activation or inactivation of the MCH system does not affect stereotyped behaviors, dopamine-related responses that depend on the activity of the nigrostriatal pathway. Furthermore MCH does not affect dizocilpine-induced PPI deficit, a glutamate related response. Thus, our data present the MCH system as a regulator of sensorimotor gating, and provide a new rationale to understand the etiologies of schizophrenia and related psychiatric disorders.     

Conspecific sperm precedence in two species of tropical sea urchins

Conspecific sperm precedence occurs when females are exposed to sperm from males of multiple species, but preferentially use sperm of a conspecific. Conspecific sperm precedence and its mechanisms have been documented widely in terrestrial species, in which complex female behaviors or reproductive tract morphologies can allow many opportunities for female choice and sperm competition, however, the opportunity for conspecific sperm precedence in free spawning marine invertebrates has been largely ignored. Two sea urchin species, Echinometra oblonga and E. sp. C, have high levels of interspecific fertilization in no-choice lab crosses, but no natural hybrids have been found. We performed competitive fertilization assays to test for conspecific sperm precedence and found that eggs of both species showed a marked preference for conspecific sperm when fertilized with heterospecific sperm mixtures. Strong rejection of heterospecific sperm would not have been predicted from no-choice assays and helps explain the lack of natural hybrids. We also found significant variation in hybridization success among crosses. Conspecific sperm precedence in free spawning invertebrates shows that the simple surfaces of eggs and sperm provide ample opportunity for egg choice and sperm competition even in the absence of intricate behavior or complex reproductive morphologies.     

Identification and characterization of keyhole limpet hemocyanin N-glycans mediating cross-reactivity with Schistosoma mansoni

Keyhole limpet hemocyanin (KLH) of the mollusc Megathura crenulata is known to serologically cross-react with Schistosoma mansoni glycoconjugates in a carbohydrate-dependent manner. To elucidate the structural basis for this cross-reactivity, KLH glycans were released from tryptic glycopeptides and fluorescently labeled. Cross-reacting glycans were identified using a polyclonal antiserum reacting with soluble S. mansoni egg antigens, isolated by a three-dimensional fractionation scheme and analyzed by different mass spectrometric techniques as well as linkage analysis and exoglycosidase treatment. The results revealed that cross-reacting species comprise approximately 4.5% of released glycans. They all represent novel types of N-glycans with a Fuc(alpha1-3)GalNAc(beta1-4)[Fuc(alpha1-3)]GlcNAc motif, which is known to occur also in schistosomal glycoconjugates. The tetrasaccharide unit is attached to the 3-linked antenna of a trimannosyl core, which can be further decorated by galactosyl residues, a xylose residue in 2-position of the central mannose and/or a fucose at the innermost N-acetylglucosamine. This study provides for the first time detailed structural data on the KLH carbohydrate entities responsible for cross-reactivity with glycoconjugates from S. mansoni.     

Identification of conjugated linoleic acid elongation and beta-oxidation products by coupled silver-ion HPLC APPI-MS

Atmospheric pressure photoionisation (APPI) was used in combination with silver-ion (Ag(+))-HPLC for detection of (conjugated) fatty acid methyl esters (FAME) by tandem-mass spectrometry. APPI-MS of methyl esters of conjugated linoleic acid showed an increase in signal-to-noise ratio by a factor of 40 compared to atmospheric pressure chemical ionization in the positive mode. It was possible to identify double bond position, configuration and chain length of FAME based on chromatographic separation and mass detection. The developed LC-MS method is useful for the analysis of CLA elongation and beta-oxidation products, especially with trans,trans-configuration, which are difficult to analyze by conventional GC-MS techniques.     

First African oryctocephalid trilobites from the Lower–Middle Cambrian boundary interval

Oryctocephalid trilobites from Lower Middle Cambrian strata of the eastern Anti-Atlas, Morocco, are the first described Oryctocephalidae known from Africa. They represent the new genus and species Shergoldiella vincenti. However, a similar species was earlier described as Tonkinella sequei Liñán et Gozalo, 1999, from coeval lower Middle Cambrian strata of the Iberian Chains, northern Spain. This Iberian species is imperfectly preserved and assigned herein to Shergoldiella with reservations. If this assignment is correct, it would reinforce earlier suggested correlations between Morocco and Spain. Nevertheless, Shergoldiella suggests a morphocline from a typical oryctocephalid-type morphology towards the Tonkinella-type morphology. Close similarity with Ovatoryctocara ovata suggests a similar stratigraphic position in accordance with earlier suggested intercontinental correlations.     

TFIIIC boxes in the genome

In this issue of Cell, Noma et al. (2006) show that B-boxes and TFIIIC limit the spread of heterochromatin at the silent mat region in the fission yeast genome. Global analysis of TFIIIC distribution revealed dispersed sites of association that coalesce at the nuclear periphery, suggesting that TFIIIC may act as a barrier throughout the genome.     

Extracellular HIV-1 Nef increases migration of monocytes

Infiltration of human immunodeficiency virus type 1 (HIV-1)-infected and uninfected monocytes/macrophages in organs and tissues is a general phenomenon observed in progression of acquired immunodeficiency syndrome (AIDS). HIV-1 protein Nef is considered as a progression factor in AIDS, and is released from HIV-1-infected cells. Here, we show that extracellular Nef increases migration of monocytes. This effect is (i) concentration-dependent, (ii) reaches the order of magnitude of that induced by formyl-methyonyl-leucyl-proline (fMLP) or CC chemokine ligand 2 (CCL2)/monocyte chemotactic protein (MCP)-1, (iii) inhibited by anti-Nef monoclonal antibodies as well as by heating, and (iv) depends on a concentration gradient of Nef. Further, Nef does not elicit monocytic THP-1 cells to express chemokines such as CCL2, macrophage inhibitory protein-1alpha (CCL3) and macrophage inhibitory protein-1beta (CCL4). These data suggest that extracellular Nef may contribute to disease progression as well as HIV-1 spreading through affecting migration of monocytes.