Genes controlling gp25/30 cell-surface molecules map to chromosomes X and Y and escape X-inactivation.

The monoclonal antibody AbO13 defines a cell-surface antigen that is expressed on most cultured human cells, but not on rodent cells. AbO13 precipitates glycoproteins of 25,000 and 30,000 mol. wt. from lysates of [3H]glucosamine-labeled human cells. Results of the serological typing of a panel of 25 rodent-human somatic cell hybrid clones show that reactivity with AbO13 segregates with the human X and Y chromosomes. The presence of either of these chromosomes is sufficient for O13 expression on the hybrid cell surface. Analysis of hybrid clones containing human X chromosomes with karyotypically defined deletions permitted the regional assignment of the X-linked gene locus controlling the expression of O13 to Xp22-pter. In addition, AbO13 is reactive with Chinese hamster-human hybrids derived from fibroblasts of a 49,XXXXX individual that contained only inactivated copies of the human X chromosome. These results suggest that the X-linked locus determining the expression of O13 is not subject to X-inactivation.     

Comparison of cytologic and genetic distances between long arm subtelomeric markers of human autosome 14 suggests uneven distribution of crossing-over

The analysis of two rodent X human somatic cell hybrids, carrying different inborn translocations of the human chromosome 14 long arm, has permitted us to narrow down the localization of the structural locus for alpha-1-antitrypsin (PI) to band 14q32.1, proximally to the highly polymorphic DNA locus D14S1 which has been localized by previous studies between 14q32.1 and 14q32.2. These data, evaluated in conjunction with other published information, suggest that the D14S1 locus is cytologically equidistant from both the PI locus and the complex locus for the immunoglobulin heavy chains (IGH) but, genetically, it appears much closer to the latter since the recombination frequency reported between the IGH complex and PI is six times greater than that between the IGH complex and D14S1 (lod score peaks respectively at 26% and 4% with narrow fiducial limits). The present report adds further strength to the frequently proposed hypothesis of a nonlinear relationship between cytologic and genetic distances of human genes. The possibility that this phenomenon may be a feature of frequent occurrence throughout the entire human genome is discussed.     

Comparison between airborne pollens in Torino and Perugia (Italy) 1982–83–84

Summary By means of two Burkard Volumetric Spore-Traps situated in the center of Torino and Perugia, pollen was sampled between March and August for three years (1982–83–84). The two pollen spectra, with special reference to trees, were compared for pollen levels and duration of season in the two cities. Comments on vegetation in and around Torino and Perugia and meteorological data are compared with the two pollen spectra.      

Inhibition of phosphodiesterase 4 modulates cytokine induction from toll like receptor activated,but not rhinovirus infected,primary human airway smooth muscle

Background

Virus-induced exacerbations of Chronic Obstructive Pulmonary Disease (COPD) are a significant health burden and occur even in those receiving the best current therapies. Rhinovirus (RV) infections are responsible for half of all COPD exacerbations. The mechanism by which exacerbations occur remains undefined, however it is likely to be due to virus-induced inflammation. Given that phophodiesterase 4 (PDE₄) inhibitors have an anti-inflammatory effect in patients with COPD they present a potential therapy prior to, and during, these exacerbations.

Methods

In the present study we investigated whether the PDE₄ inhibitor piclamilast (10^-6 M) could alter RV or viral mimetic (5 μg/mL of imiquimod or poly I:C) induced inflammation and RV replication in primary human airway smooth muscle cells (ASMC) and bronchial epithelial cells (HBEC). The mediators IL-6, IL-8, prostaglandin E₂ and cAMP production were assayed by ELISA and RV replication was assayed by viral titration.

Results

We found that in ASMCs the TLR3 agonist poly I:C induced IL-8 release was reduced while induced IL-6 release by the TLR7/8 agonist imiquimod was further increased by the presence of piclamilast. However, in RV infected ASMCs, virus replication and induced mediator release were unaltered by piclamilast, as was also found in HBECs. The novel findings of this study reveal that although PDE inhibitors may not influence RV-induced cytokine production in ASMCs and replication in either ASMCs or HBECs, they have the capacity to be anti-inflammatory during TLR activation by modulating the induction of these chemotactic cytokines.

Conclusion

By extrapolating our in vitro findings to exacerbations of COPD in vivo this suggests that PDE₄ inhibitors may have beneficial anti-inflammatory properties when patients are infected with bacteria or viruses other than RV.     

Nine new polymorphic microsatellite loci for the amplification of archived otolith DNA of Atlantic cod,Gadus morhua L.

Nine out of 22 microsatellite primers tested were successfully amplified on three samples of cod Gadus morhua L. (two contemporary and one archived otolith samples). All loci were polymorphic (5–23 alleles/locus). The average observed heterozygosity across loci and samples was 0.625, ranging from 0.294 to 0.895 at each locus. All loci were under Hardy–Weinberg equilibrium, except PGmo56 that showed significant excess of heterozygotes in all studied samples. The isolated loci were suitable for degraded DNA and therefore useful for conducting a long‐term temporal study with DNA obtained from archived otoliths of cod.     

The blockade of the transient receptor potential vanilloid type 1 and fatty acid amide hydrolase decreases symptoms and central sequelae in the medial prefrontal cortex of neuropathic rats

Background

Neuropathic pain is a chronic disease resulting from dysfunction within the "pain matrix". The basolateral amygdala (BLA) can modulate cortical functions and interactions between this structure and the medial prefrontal cortex (mPFC) are important for integrating emotionally salient information. In this study, we have investigated the involvement of the transient receptor potential vanilloid type 1 (TRPV1) and the catabolic enzyme fatty acid amide hydrolase (FAAH) in the morphofunctional changes occurring in the pre-limbic/infra-limbic (PL/IL) cortex in neuropathic rats.

Results

The effect of N-arachidonoyl-serotonin (AA-5-HT), a hybrid FAAH inhibitor and TPRV1 channel antagonist, was tested on nociceptive behaviour associated with neuropathic pain as well as on some phenotypic changes occurring on PL/IL cortex pyramidal neurons. Those neurons were identified as belonging to the BLA-mPFC pathway by electrical stimulation of the BLA followed by hind-paw pressoceptive stimulus application. Changes in their spontaneous and evoked activity were studied in sham or spared nerve injury (SNI) rats before or after repeated treatment with AA-5-HT. Consistently with the SNI-induced changes in PL/IL cortex neurons which underwent profound phenotypic reorganization, suggesting a profound imbalance between excitatory and inhibitory responses in the mPFC neurons, we found an increase in extracellular glutamate levels, as well as the up-regulation of FAAH and TRPV1 in the PL/IL cortex of SNI rats. Daily treatment with AA-5-HT restored cortical neuronal activity, normalizing the electrophysiological changes associated with the peripheral injury of the sciatic nerve. Finally, a single acute intra-PL/IL cortex microinjection of AA-5-HT transiently decreased allodynia more effectively than URB597 or I-RTX, a selective FAAH inhibitor or a TRPV1 blocker, respectively.

Conclusion

These data suggest a possible involvement of endovanilloids in the cortical plastic changes associated with peripheral nerve injury and indicate that therapies able to normalize endovanilloid transmission may prove useful in ameliorating the symptoms and central sequelae associated with neuropathic pain.     

A global view of the OCA2-HERC2 region and pigmentation

Mutations in the gene OCA2 are responsible for oculocutaneous albinism type 2, but polymorphisms in and around OCA2 have also been associated with normal pigment variation. In Europeans, three haplotypes in the region have been shown to be associated with eye pigmentation and a missense SNP (rs1800407) has been associated with green/hazel eyes (Branicki et al. in Ann Hum Genet 73:160-170, 2009). In addition, a missense mutation (rs1800414) is a candidate for light skin pigmentation in East Asia (Yuasa et al. in Biochem Genet 45:535-542, 2007; Anno et al. in Int J Biol Sci 4, 2008). We have genotyped 3,432 individuals from 72 populations for 21 SNPs in the OCA2-HERC2 region including those previously associated with eye or skin pigmentation. We report that the blue-eye associated alleles at all three haplotypes were found at high frequencies in Europe; however, one is restricted to Europe and surrounding regions, while the other two are found at moderate to high frequencies throughout the world. We also observed that the derived allele of rs1800414 is essentially limited to East Asia where it is found at high frequencies. Long-range haplotype tests provide evidence of selection for the blue-eye allele at the three haplotyped systems but not for the green/hazel eye SNP allele. We also saw evidence of selection at the derived allele of rs1800414 in East Asia. Our data suggest that the haplotype restricted to Europe is the strongest marker for blue eyes globally and add further inferential evidence that the derived allele of rs1800414 is an East Asian skin pigmentation allele.     

In situ mapping of the gene coding for a leucine zipper DNA binding protein (CDR62) to 16p12–16p13.1

A cDNA clone encoding the major antigen (CDR62) associated with the antibody-induced paraneoplastic cerebellar degeneration has been used to identify the chromosomal location of the corresponding structural gene(s) by screening for its retention in a panel of rodent-human somatic cell hybrids. Having established the synteny of the gene with the autosome 16, we proceeded to its precise subregional mapping by in situ fluorescence hybridization with a recombinant lambda phage containing the genomic region homologous to the cDNA gene. The latter studies pin-pointed the chromosomal localization of the structural CDR62 gene within the interval 16p12-16p13.1.     

European larch phenology in the Alps: can we grasp the role of ecological factors by combining field observations and inverse modelling?

Vegetation phenology is strongly influenced by climatic factors. Climate changes may cause phenological variations, especially in the Alps which are considered to be extremely vulnerable to global warming. The main goal of our study is to analyze European larch (Larix decidua Mill.) phenology in alpine environments and the role of the ecological factors involved, using an integrated approach based on accurate field observations and modelling techniques. We present 2 years of field-collected larch phenological data, obtained following a specifically designed observation protocol. We observed that both spring and autumn larch phenology is strongly influenced by altitude. We propose an approach for the optimization of a spring warming model (SW) and the growing season index model (GSI) consisting of a model inversion technique, based on simulated look-up tables (LUTs), that provides robust parameter estimates. The optimized models showed excellent agreement between modelled and observed data: the SW model predicts the beginning of the growing season (B(GS)) with a mean RMSE of 4 days, while GSI gives a prediction of the growing season length (L(GS)) with a RMSE of 5 days. Moreover, we showed that the original GSI parameters led to consistent errors, while the optimized ones significantly increased model accuracy. Finally, we used GSI to investigate interactions of ecological factors during springtime development and autumn senescence. We found that temperature is the most effective factor during spring recovery while photoperiod plays an important role during autumn senescence: photoperiod shows a contrasting effect with altitude decreasing its influence with increasing altitude.