Generic finite-size enhancement of pairing in mesoscopic Fermi systems

The finite-size-dependent enhancement of pairing in mesoscopic Fermi systems is studied under the assumption that the BCS approach is valid and that the two-body force is size independent. Different systems are investigated such as superconducting metallic grains and films as well as atomic nuclei. It is shown that the finite size enhancement of pairing in these systems is in part due to the presence of a surface which accounts quite well for the data of nuclei and explains a good fraction of the enhancement in Al grains.

Pairing with polarization effects in low-density neutron matter

We study the properties of the 1S0 pairing gap in low-density neutron matter. Different corrections to the lowest-order scattering length approximation are explored, resulting in a strong suppression with respect to the BCS result.

Nuclear pairing: surface or bulk?

We analyze how the spatial localization properties of pairing correlations are changing in a major neutron shell of heavy nuclei. It is shown that the radial distribution of the pairing density depends strongly on whether the chemical potential is close to a low or a high angular momentum level and has little sensitivity to whether the pairing force acts at the surface or in the bulk. The pairing density averaged over one major shell is, however, rather flat, exhibiting little dependence on the pairing force. Hartree-Fock-Bogoliubov calculations for the isotopic chain 100-132Sn are presented for demonstration purposes.

Density matrix functional theory that includes pairing correlations

The extension of density functional theory (DFT) to include pairing correlations without formal violation of the particle-number conservation condition is described. This version of the theory can be considered as a foundation of the application of existing DFT plus pairing approaches to atoms, molecules, ultracooled and magnetically trapped atomic Fermi gases, and atomic nuclei where the number of particles is conserved exactly. The connection with Hartree-Fock-Bogoliubov (HFB) theory is discussed, and the method of quasilocal reduction of the nonlocal theory is also described. This quasilocal reduction allows equations of motion to be obtained which are much simpler for numerical solution than the equations corresponding to the nonlocal case. Our theory is applied to the study of some even Sn isotopes, and the results are compared with those obtained in the standard HFB theory and with the experimental ones.

Functional genomics of the Drosophila melanogaster X chromosome and the role of DWnt5 during development

The collection of X chromosome insertions (PX) lethal lines, which was isolated from a screen for essential genes on the X chromosome, was characterized by means of cloning the insertion sites, mapping the sites within genomic DNA and determination of the associated reporter gene expresssion patterns. The established STS flanking the P element insertion sites were submitted to EMBL nucleotide databases and their in situ data together with the enhancer trap expression patterns have been deposited in the FlyView database. The characterized lines are now available to be used by the scientific community for a detailed analysis of the newly established lethal gene functions. One of the isolated genes on the X chromosome was the Drosophila gene Wnt5 (DWnt5). From two independent screens, one lethal and three homozygous viable alleles were recovered, allowing the identification of two distinct functions for DWnt5 in the fly. Observations on the developing nervous system of mutant embryos suggest that DWnt5 activity affects axon projection pattern. Elevated levels of DWNT5 activity in the midline cells of the central nervous system causes improper establishment and maintenance of the axonal pathways. Our analysis of the expression and mutant phenotype indicates that DWnt5 function in a process needed for proper organization of the nervous system. A second and novel function of DWnt5 is the control of the body size by regulation of the cell number rather than affecting the size of cells. Moreover, experimentally increased DWnt5 levels in a post-mitotic region of the eye imaginal disc causes abnormal cell cycle progression, resulting in additional ommatidia in the adult eye when compared to wild type. The increased cell number and the effects on the cell cycle after exposure to high DWNT5 levels is the result of a failure to downregulate cyclin B and therefore the unsuccessful establishment of a G1 arrest.

Retargeting of pre-set regions on chromosome for high gene expression in mammalian cells

We have developed a system to hunt and reuse special gene integration sites that allow for high and stable gene expression. A vector, named pRGFP8, was constructed. The plasmid pRGFP8 contains a reporter gene, gfp2 and two extraneous DNA fragments. The gene gfp2 makes it possible to screen the high expression regions on the chromosome. The extraneous DNA fragments can help to create the unique loci on the chromosome and increase the gene targeting frequency by increasing the homology. After transfection into Chinese hamster ovary cells (CHO) cells, the linearized pRGFP8 can integrate into the chromosome of the host cells and form the unique sites. With FACS, 90 millions transfected cells were sorted and the cells with strongest GFP expression were isolated, and then 8 stable high expression GFP CHO cell lines were selected as candidates for the new host cell. Taking the unique site created by pRGFP8 on the chromosome in the new host cells as a targeting locus, the gfp2 gene was replaced with the gene of interest, human ifngamma, by transfecting the targeting plasmid pRIH-IFN. Then using FACS, the cells with the dimmest GFP fluorescence were selected. These cells showed they had strong abilities to produce the protein of interest, IFN-gamma. During the gene targeting experiment, we found there is positive correlation between the fluorescence density of the GFP CHO host cells and the specific production rate of IFN-gamma. This result shows that the strategy in our expression system is correct: the production of the interesting protein increases with the increase fluorescence of the GFP host cells. This system, the new host cell lines and the targeting vector, can be utilized for highly expressing the gene of interest. More importantly, by using FACS, we can fully screen all the transfected cells, which can reduce the chances of losing the best cells.

"Refined mapping of a quantitative trait locus on chromosome 1 responsible for mouse embryonic death"

Recurrent spontaneous abortion (RSA) is defined as the loss of three or more consecutive pregnancies during the first trimester of embryonic intrauterine development. This kind of human infertility is frequent among the general population since it affects 1 to 5% of women. In half of the cases the etiology remains unelucidated. In the present study, we used interspecific recombinant congenic mouse strains (IRCS) in the aim to identify genes responsible for embryonic lethality. Applying a cartographic approach using a genotype/phenotype association, we identified a minimal QTL region, of about 6 Mb on chromosome 1, responsible for a high rate of embryonic death (,30%). Genetic analysis suggests that the observed phenotype is linked to uterine dysfunction. Transcriptomic analysis of the uterine tissue revealed a preferential deregulation of genes of this region compared to the rest of the genome. Some genes from the QTL region are associated with VEGF signaling, mTOR signaling and ubiquitine/proteasome-protein degradation pathways. This work may contribute to elucidate the molecular basis of a multifactorial and complex human disorder as RSA.

"Genome-Wide Linkage in a Highly Consanguineous Pedigree Reveals Two Novel Loci on Chromosome 7 for Non-Syndromic Familial Premature Ovarian Failure"

Background: The human condition known as Premature Ovarian Failure (POF) is characterized by loss of ovarian function before the age of 40. A majority of POF cases are sporadic, but 10–15% are familial, suggesting a genetic origin of the disease. Although several causal mutations have been identified, the etiology of POF is still unknown for about 90% of the patients. Methodology/Principal Findings: We report a genome-wide linkage and homozygosity analysis in one large consanguineous Middle-Eastern POF-affected family presenting an autosomal recessive pattern of inheritance. We identified two regions with a LODmax of 3.26 on chromosome 7p21.1-15.3 and 7q21.3-22.2, which are supported as candidate regions by homozygosity mapping. Sequencing of the coding exons and known regulatory sequences of three candidate genes (DLX5, DLX6 and DSS1) included within the largest region did not reveal any causal mutations. Conclusions/Significance: We detect two novel POF-associated loci on human chromosome 7, opening the way to the identification of new genes involved in the control of ovarian development and function.

Refined mapping of a quantitative trait locus on chromosome 1 responsible for mouse embryonic death

Recurrent spontaneous abortion (RSA) is defined as the loss of three or more consecutive pregnancies during the first trimester of embryonic intrauterine development. This kind of human infertility is frequent among the general population since it affects 1 to 5% of women. In half of the cases the etiology remains unelucidated. In the present study, we used interspecific recombinant congenic mouse strains (IRCS) in the aim to identify genes responsible for embryonic lethality. Applying a cartographic approach using a genotype/phenotype association, we identified a minimal QTL region, of about 6 Mb on chromosome 1, responsible for a high rate of embryonic death (similar to 30%). Genetic analysis suggests that the observed phenotype is linked to uterine dysfunction. Transcriptomic analysis of the uterine tissue revealed a preferential deregulation of genes of this region compared to the rest of the genome. Some genes from the QTL region are associated with VEGF signaling, mTOR signaling and ubiquitine/proteasome-protein degradation pathways. This work may contribute to elucidate the molecular basis of a multifactorial and complex human disorder as RSA.

A novel variant on chromosome 7q22.3 associated with mean platelet volume, counts, and function

Mean platelet volume (MPV) and platelet count (PLT) are highly heritable and tightly regulated traits. We performed a genome-wide association study for MPV and identified one SNP, rs342293, as having highly significant and reproducible association with MPV (per-G allele effect 0.016 +/- 0.001 log fL; P < 1.08 x 10(-24)) and PLT (per-G effect -4.55 +/- 0.80 10(9)/L; P < 7.19 x 10(-8)) in 8586 healthy subjects. Whole-genome expression analysis in the 1-MB region showed a significant association with platelet transcript levels for PIK3CG (n = 35; P = .047). The G allele at rs342293 was also associated with decreased binding of annexin V to platelets activated with collagen-related peptide (n = 84; P = .003). The region 7q22.3 identifies the first QTL influencing platelet volume, counts, and function in healthy subjects. Notably, the association signal maps to a chromosome region implicated in myeloid malignancies, indicating this site as an important regulatory site for hematopoiesis. The identification of loci regulating MPV by this and other studies will increase our insight in the processes of megakaryopoiesis and proplatelet formation, and it may aid the identification of genes that are somatically mutated in essential thrombocytosis. (Blood. 2009; 113: 3831-3837)

Amino acid pairing preferences in parallel beta-sheets in proteins

Statistical approaches have been applied to examine amino acid pairing preferences within parallel beta-sheets. The main chain hydrogen bonding pattern in parallel beta-sheets means that, for each residue pair, only one of the residues is involved in main chain hydrogen bonding with the strand containing the partner residue. We call this the hydrogen bonded (HB) residue and the partner residue the non-hydrogen bonded (nHB) residue, and differentiate between the favorability of a pair and that of its reverse pair, e.g. Asn(HB)-Thr(nHB)versus Thr(HB)-Asn(nHB). Significantly (p < or = 0.000001) favoured pairings were rationalised using stereochemical arguments. For instance, Asn(HB)-Thr(nHB) and Arg(HB)-Thr(nHB) were favoured pairs, where the residues adopted favoured chi1 rotamer positions that allowed side-chain interactions to occur. In contrast, Thr(HB)-Asn(nHB) and Thr(HB)-Arg(nHB) were not significantly favoured, and could only form side-chain interactions if the residues involved adopted less favourable chi1 conformations. The favourability of hydrophobic pairs e.g. Ile(HB)-Ile(nHB), Val(HB)-Val(nHB) and Leu(HB)-Ile(nHB) was explained by the residues adopting their most preferred chi1 and chi2 conformations, which enabled them to form nested arrangements. Cysteine-cysteine pairs are significantly favoured, although these do not form intrasheet disulphide bridges. Interactions between positively and negatively charged residues were asymmetrically preferred: those with the negatively charged residue at the HB position were more favoured. This trend was accounted for by the presence of general electrostatic interactions, which, based on analysis of distances between charged atoms, were likely to be stronger when the negatively charged residue is the HB partner. The Arg(HB)-Asp(nHB) interaction was an exception to this trend and its favorability was rationalised by the formation of specific side-chain interactions. This research provides rules that could be applied to protein structure prediction, comparative modelling and protein engineering and design. The methods used to analyse the pairing preferences are automated and detailed results are available (http://www.rubic.rdg.ac.uk/betapairprefsparallel/).