Innate versus learned odour processing in the mouse olfactory bulb

The mammalian olfactory system mediates various responses, including aversive behaviours to spoiled foods and fear responses to predator odours. In the olfactory bulb, each glomerulus represents a single species of odorant receptor. Because a single odorant can interact with several different receptor species, the odour information received in the olfactory epithelium is converted to a topographical map of multiple glomeruli activated in distinct areas in the olfactory bulb. To study how the odour map is interpreted in the brain, we generated mutant mice in which olfactory sensory neurons in a specific area of the olfactory epithelium are ablated by targeted expression of the diphtheria toxin gene. Here we show that, in dorsal-zone-depleted mice, the dorsal domain of the olfactory bulb was devoid of glomerular structures, although second-order neurons were present in the vacant areas. The mutant mice lacked innate responses to aversive odorants, even though they were capable of detecting them and could be conditioned for aversion with the remaining glomeruli. These results indicate that, in mice, aversive information is received in the olfactory bulb by separate sets of glomeruli, those dedicated for innate and those for learned responses.     

Metabolic priming by a secreted fungal effector

Maize smut caused by the fungus Ustilago maydis is a widespread disease characterized by the development of large plant tumours. U. maydis is a biotrophic pathogen that requires living plant tissue for its development and establishes an intimate interaction zone between fungal hyphae and the plant plasma membrane. U. maydis actively suppresses plant defence responses by secreted protein effectors. Its effector repertoire comprises at least 386 genes mostly encoding proteins of unknown function and expressed exclusively during the biotrophic stage. The U. maydis secretome also contains about 150 proteins with probable roles in fungal nutrition, fungal cell wall modification and host penetration as well as proteins unlikely to act in the fungal-host interface like a chorismate mutase. Chorismate mutases are key enzymes of the shikimate pathway and catalyse the conversion of chorismate to prephenate, the precursor for tyrosine and phenylalanine synthesis. Root-knot nematodes inject a secreted chorismate mutase into plant cells likely to affect development. Here we show that the chorismate mutase Cmu1 secreted by U. maydis is a virulence factor. The enzyme is taken up by plant cells, can spread to neighbouring cells and changes the metabolic status of these cells through metabolic priming. Secreted chorismate mutases are found in many plant-associated microbes and might serve as general tools for host manipulation.     

The role of Epac in the heart

As one of the most important second messengers, 3′,5′-cyclic adenosine monophosphate (cAMP) mediates various extracellular signals including hormones and neurotransmitters, and induces appropriate responses in diverse types of cells. Since cAMP was formerly believed to transmit signals through only two direct target molecules, protein kinase A and the cyclic nucleotide-gated channel, the sensational discovery in 1998 of another novel direct effecter of cAMP [exchange proteins directly activated by cAMP (Epac)] attracted a great deal of scientific interest in cAMP signaling. Numerous studies on Epac have since disclosed its important functions in various tissues in the body. Recently, observations of genetically manipulated mice in various pathogenic models have begun to reveal the in vivo significance of previous in vitro or cellular-level findings. Here, we focused on the function of Epac in the heart. Accumulating evidence has revealed that both Epac1 and Epac2 play important roles in the structure and function of the heart under physiological and pathological conditions. Accordingly, developing the ability to regulate cAMP-mediated signaling through Epac may lead to remarkable new therapies for the treatment of cardiac diseases.     

Recombinant expression of perchloric acid-soluble protein reduces cell proliferation

Perchloric acid-soluble protein (PSP) may play an important role in the regulation of cellular physiological functions because it has been highly conserved throughout evolution; however, this role has not been well elucidated. In previous reports, we suggested that PSP regulates cell proliferation. In this study, we examined the effect of PSP expression on proliferation of the normal rat kidney cell line NRK-52E, the rat hepatocyte cell line RLN-10, and the rat hepatoma cell line dRLh-84. Cells transfected with pcDNA-sense-PSP (pcDNA-S-PSP) over-expressed PSP mRNA and protein, and cell proliferation of the transfected cells was suppressed compared with that of cells transfected with pcDNA-empty (pcDNA-E). Cell viability of pcDNA-S-PSP-transfected cells was similar to that of pcDNA-E-transfected cells. Thus, over-expression of PSP suppresses cell proliferation without any influence on cell viability. These findings are the first to report an inhibitory activity of PSP on cell proliferation. Received 27 April 2001; received after revision 8 June 2001; accepted 8 June 2001     

Expression and cellular distribution of perchloric acid-soluble protein is dependent on the cell-proliferating states of NRK-52E cells

To clarify the biological role of kidney perchloric acid-soluble protein 1 (K-PSP1), its expression and intracellular distribution were examined in normal rat kidney epithelial NRK-52E cells. K-PSP1 expression was low during the proliferating phase and high in the stationary phase, and shown to have a negative relationship with the protein-synthesizing activity of the cells. Immunocytochemical studies revealed that K-PSP1 is predominantly located in the cytosol, especially in endoplasmic reticulum and Golgi apparatus of proliferating cells. In the stationary phase, K-PSP1 was not detected immunologically even though protein and mRNA expression were high. This disappearance of reactivity with anti-serum seems to be due to a conformational change in K-PSP1 induced by unknown factors. These results suggest that the role of K-PSP1 is to regulate cell proliferation, and this may be related to a previously reported ability to inhibit protein synthesis.     

Regulated expression and neural functions of human natural killer-1 (HNK-1) carbohydrate

Human natural killer-1 (HNK-1) carbohydrate, comprising a unique trisaccharide HSO₃-3GlcAβ1-3Galβ1-4GlcNAc, shows well-regulated expression and unique functions in the nervous system. Recent studies have revealed sophisticated and complicated expression mechanisms for HNK-1 glycan. Activities of biosynthetic enzymes are controlled through the formation of enzyme-complexes and regulation of subcellular localization. Functional aspects of HNK-1 carbohydrate were examined by overexpression, knockdown, and knockout studies of these enzymes. HNK-1 is involved in several neural functions such as synaptic plasticity, learning and memory, and the underlying molecular mechanisms have been illustrated upon identification of the target carrier glycoproteins of HNK-1 such as the glutamate receptor subunit GluA2 or tenascin-R. In this review, we describe recent findings about HNK-1 carbohydrate that provide further insights into the mechanism of its expression and function in the nervous system.     

Role of active oxygen species in diethyldithiocarbamate-induced gastric ulcer in the rat

Diethyldithiocarbamate, an inhibitor of Cu,Zn-superoxide dismutase, was recently found to be ulcerogenic in the rat stomach, and active oxygen species were found to be responsible for its ulcerogenicity. To clarify which active oxygen species play a role in ulcerogenesis, the effects of various scavengers and iron-chelators were studied. As superoxide dismutase and catalase reduced the ulcerogenesis induced by diethyldithiocarbamate, the superoxide radical and hydrogen peroxide were considered to play a pathogenic role in this ulcer model.     

Loss of Siglec-14 reduces the risk of chronic obstructive pulmonary disease exacerbation

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. COPD exacerbation, or episodic worsening of symptoms, often results in hospitalization and increased mortality rates. Airway infections by new bacterial strains, such as nontypeable Haemophilus influenzae (NTHi), are a major cause of COPD exacerbation. NTHi express lipooligosaccharides that contain sialic acids, and may interact with Siglec-14, a sialic acid recognition protein on myeloid cells that serves as an activating signal transduction receptor. A null allele polymorphism in SIGLEC14 may attenuate the inflammatory responses to NTHi by eliminating Siglec-14 expression. We asked if the loss of Siglec-14 attenuates the inflammatory response by myeloid cells against NTHi, and if the SIGLEC14-null polymorphism has any effect on COPD exacerbation. We found that NTHi interacts with Siglec-14 to enhance proinflammatory cytokine production in a tissue culture model. Inhibitors of the Syk tyrosine kinase suppress this response. Loss of Siglec-14, due to SIGLEC14-null allele homozygosity, is associated with a reduced risk of COPD exacerbation in a Japanese patient population. Taken together, Siglec-14 and its downstream signaling pathway facilitate the “infection–inflammation–exacerbation” axis of COPD disease progression, and may represent promising targets for therapeutic intervention.     

Photonics: lasers producing tailored beams

Compact lasers that can produce a range of beam patterns are important for progress in several areas, including the improvement of optical tweezers, ultra-high-density optical memory and microfluidics. Here we engineer photonic crystals to generate semiconductor lasers that produce a range of beam patterns while maintaining stable single-mode oscillation. Our results could contribute to the realization of compact lasers that are capable of producing diverse beam patterns on demand.