Neuronal plasticity and regeneration in the olfactory system of mammals: morphological and functional recovery following olfactory bulb deafferentation

The mammalian olfactory system has the unique property in the permanent turnover of the olfactory sensory neurons under normal conditions and following injury. This implies that the topographical map of the epithelium-to-bulb connections generated during ontogenesis has to be maintained despite neuron renewal in order to insure olfactory information processing. One way to investigate this issue has been to disrupt the peripheral connections and analyze how neural connections may be reestablished as well as how animals may perform in olfactory-mediated tasks. This review surveys the main data pertaining to both morphological and functional recoveries taking place in the peripheral olfactory system following olfactory bulb deafferentation. Conclusions from these studies are enlightened by recent data from molecular biology.     

Phylogeography of crossbills, bullfinches, grosbeaks, and rosefinches

Mitochondrial cytochrome b (cyt b) from 24 Carduelini species including crossbills, bullfinches, grosbeaks, rosefinches, and other related, but not conclusively classified species, was sequenced. These sequences were also compared with all the available sequences from the genera Carduelis, Serinus, and Passer. Phylogenetic analyses consistently gave the same groups of finches and the calculated divergence times suggest that speciation of the studied species occurred between 14 and 3 million years ago (Miocene-Pliocene), appearing before the Passer, Carduelis, and Serinus genera. Pleistocene glaciations may have been important in sub-speciation. Crossbills are integrated within the genus Carduelis, and within redpolls; the common crossbill shows subspeciation with Loxia japonica in the Pleistocene epoch. Pinicola enucleator groups together with bullfinches and is probably the ancestor of the group. Hawfinch is only distantly related to the studied groups, and might either represent an isolated genus or be related to the New World genus Hesperiphona. The grosbeak genera Eophona and Mycerobas are clearly sister groups, and species belonging to the former might have given rise to Mycerobas species. The isolated (in classification) Uragus sibiricus and Haematospiza sipahi are included within the genus Carpodacus (rosefinches); Carpodacus nipalensis is outside the genus Carpodacus in the molecular analyses and might be an isolated species or related to the genus Montifringilla.     

Genetic evidence against panmixia in the European eel

The panmixia hypothesis--that all European eel (Anguilla anguilla) migrate to the Sargasso Sea for reproduction and comprise a single, randomly mating population--is widely accepted. If true, then this peculiar life history strategy would directly impact the population genetics of this species, and eels from European and north African rivers should belong to the same breeding population through the random dispersal of larvae. To date, the panmixia hypothesis has remained unchallenged: genetic studies realized on eel's mitochondrial DNA failed to detect any genetic structure; and a similar lack of structure was found using allozymes, with the exception of clinal variation imposed by selection. Here we have used highly polymorphic genetic markers that provide better resolution to investigate genetic structure in European eel. Analysis of seven microsatellite loci among 13 samples from the north Atlantic, the Baltic Sea and the Mediterranean Sea basins reveals that there is global genetic differentiation. Moreover, pairwise Cavalli-Sforza and Edwards chord distances correlate significantly with coastal geographical distance. This pattern of genetic structure implies non-random mating and restricted gene flow among eels from different sampled locations, which therefore refute the hypothesis of panmixia. Consequently, the reproductive biology of European eel must be reconsidered.     

Recognition of haemagglutinins on virus-infected cells by NKp46 activates lysis by human NK cells

Natural killer (NK) cells destroy virus-infected and tumour cells, apparently without the need for previous antigen stimulation. In part, target cells are recognized by their diminished expression of major histocompatibility complex (MHC) class I molecules, which normally interact with inhibitory receptors on the NK cell surface. NK cells also express triggering receptors that are specific for non-MHC ligands; but the nature of the ligands recognized on target cells is undefined. NKp46 is thought to be the main activating receptor for human NK cells. Here we show that a soluble NKp46-immunoglobulin fusion protein binds to both the haemagglutinin of influenza virus and the haemagglutinin-neuraminidase of parainfluenza virus. In a substantial subset of NK cells, recognition by NKp46 is required to lyse cells expressing the corresponding viral glycoproteins. The binding requires the sialylation of NKp46 oligosaccharides, which is consistent with the known sialic binding capacity of the viral glycoproteins. These findings indicate how NKp46-expressing NK cells may recognize target cells infected by influenza or parainfluenza without the decreased expression of target-cell MHC class I protein.     

Observation of coherent optical information storage in an atomic medium using halted light pulses

Electromagnetically induced transparency is a quantum interference effect that permits the propagation of light through an otherwise opaque atomic medium; a 'coupling' laser is used to create the interference necessary to allow the transmission of resonant pulses from a 'probe' laser. This technique has been used to slow and spatially compress light pulses by seven orders of magnitude, resulting in their complete localization and containment within an atomic cloud. Here we use electromagnetically induced transparency to bring laser pulses to a complete stop in a magnetically trapped, cold cloud of sodium atoms. Within the spatially localized pulse region, the atoms are in a superposition state determined by the amplitudes and phases of the coupling and probe laser fields. Upon sudden turn-off of the coupling laser, the compressed probe pulse is effectively stopped; coherent information initially contained in the laser fields is 'frozen' in the atomic medium for up to 1 ms. The coupling laser is turned back on at a later time and the probe pulse is regenerated: the stored coherence is read out and transferred back into the radiation field. We present a theoretical model that reveals that the system is self-adjusting to minimize dissipative loss during the 'read' and 'write' operations. We anticipate applications of this phenomenon for quantum information processing.     

Genome sequence of enterohaemorrhagic Escherichia coli O157:H7

The bacterium Escherichia coli O157:H7 is a worldwide threat to public health and has been implicated in many outbreaks of haemorrhagic colitis, some of which included fatalities caused by haemolytic uraemic syndrome. Close to 75,000 cases of O157:H7 infection are now estimated to occur annually in the United States. The severity of disease, the lack of effective treatment and the potential for large-scale outbreaks from contaminated food supplies have propelled intensive research on the pathogenesis and detection of E. coli O157:H7 (ref. 4). Here we have sequenced the genome of E. coli O157:H7 to identify candidate genes responsible for pathogenesis, to develop better methods of strain detection and to advance our understanding of the evolution of E. coli, through comparison with the genome of the non-pathogenic laboratory strain E. coli K-12 (ref. 5). We find that lateral gene transfer is far more extensive than previously anticipated. In fact, 1,387 new genes encoded in strain-specific clusters of diverse sizes were found in O157:H7. These include candidate virulence factors, alternative metabolic capacities, several prophages and other new functions--all of which could be targets for surveillance.     

The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy

Hereditary inclusion body myopathy (HIBM; OMIM 600737) is a unique group of neuromuscular disorders characterized by adult onset, slowly progressive distal and proximal weakness and a typical muscle pathology including rimmed vacuoles and filamentous inclusions. The autosomal recessive form described in Jews of Persian descent is the HIBM prototype. This myopathy affects mainly leg muscles, but with an unusual distribution that spares the quadriceps. This particular pattern of weakness distribution, termed quadriceps-sparing myopathy (QSM), was later found in Jews originating from other Middle Eastern countries as well as in non-Jews. We previously localized the gene causing HIBM in Middle Eastern Jews on chromosome 9p12-13 (ref. 5) within a genomic interval of about 700 kb (ref. 6). Haplotype analysis around the HIBM gene region of 104 affected people from 47 Middle Eastern families indicates one unique ancestral founder chromosome in this community. By contrast, single non-Jewish families from India, Georgia (USA) and the Bahamas, with QSM and linkage to the same 9p12-13 region, show three distinct haplotypes. After excluding other potential candidate genes, we eventually identified mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) gene in the HIBM families: all patients from Middle Eastern descent shared a single homozygous missense mutation, whereas distinct compound heterozygotes were identified in affected individuals of families of other ethnic origins. Our findings indicate that GNE is the gene responsible for recessive HIBM.     

Mutant beta-spectrin 4 causes auditory and motor neuropathies in quivering mice

The autosomal recessive mouse mutation quivering (qv), which arose spontaneously in 1953, produces progressive ataxia with hind limb paralysis, deafness and tremor. Six additional spontaneous alleles, qvJ, qv2J, qv3J, qv4J, qvlnd and qvlnd2J, have been identified. Ear twitch responses (Preyer's reflex) to sound are absent in homozygous qv/qv mice, although cochlear morphology seems normal and cochlear potentials recorded at the round window are no different from those of control mice. However, responses from brainstem auditory nuclei show abnormal transmission of auditory information, indicating that, in contrast to the many known mutations causing deafness originating in the cochlea, deafness in qv is central in origin. Here we report that quivering mice carry loss-of-function mutations in the mouse beta-spectrin 4 gene (Spnb4) that cause alterations in ion channel localization in myelinated nerves; this provides a rationale for the auditory and motor neuropathies of these mice.     

Identification of the platelet ADP receptor targeted by antithrombotic drugs

Platelets have a crucial role in the maintenance of normal haemostasis, and perturbations of this system can lead to pathological thrombus formation and vascular occlusion, resulting in stroke, myocardial infarction and unstable angina. ADP released from damaged vessels and red blood cells induces platelet aggregation through activation of the integrin GPIIb-IIIa and subsequent binding of fibrinogen. ADP is also secreted from platelets on activation, providing positive feedback that potentiates the actions of many platelet activators. ADP mediates platelet aggregation through its action on two G-protein-coupled receptor subtypes. The P2Y1 receptor couples to Gq and mobilizes intracellular calcium ions to mediate platelet shape change and aggregation. The second ADP receptor required for aggregation (variously called P2Y(ADP), P2Y(AC), P2Ycyc or P2T(AC)) is coupled to the inhibition of adenylyl cyclase through Gi. The molecular identity of the Gi-linked receptor is still elusive, even though it is the target of efficacious antithrombotic agents, such as ticlopidine and clopidogrel and AR-C66096 (ref. 9). Here we describe the cloning of this receptor, designated P2Y12, and provide evidence that a patient with a bleeding disorder has a defect in this gene. Cloning of the P2Y12 receptor should facilitate the development of better antiplatelet agents to treat cardiovascular diseases.