Combinatorial Conflicting Homozygosity (CCH) analysis enables the rapid identification of shared genomic regions in the presence of multiple phenocopies.

The ability to identify regions of the genome inherited with a dominant trait in one or more families has become increasingly valuable with the wide availability of high throughput sequencing technology. While a number of methods exist for mapping of homozygous variants segregating with recessive traits in consanguineous families, dominant conditions are conventionally analysed by linkage analysis, which requires computationally demanding haplotype reconstruction from marker genotypes and, even using advanced parallel approximation implementations, can take substantial time, particularly for large pedigrees. In addition, linkage analysis lacks sensitivity in the presence of phenocopies (individuals sharing the trait but not the genetic variant responsible). Combinatorial Conflicting Homozygosity (CCH) analysis uses high density biallelic single nucleotide polymorphism (SNP) marker genotypes to identify genetic loci within which consecutive markers are not homozygous for different alleles. This allows inference of identical by descent (IBD) inheritance of a haplotype among a set or subsets of related or unrelated individuals

A novel COL4A1 frameshift mutation in familial kidney disease: the importance of the C-terminal NC1 domain of type IV collagen

BACKGROUND: Hereditary microscopic haematuria often segregates with mutations of COL4A3, COL4A4 or COL4A5 but in half of families a gene is not identified. We investigated a Cypriot family with autosomal dominant microscopic haematuria with renal failure and kidney cysts. METHODS: We used genome-wide linkage analysis, whole exome sequencing and cosegregation analyses. RESULTS: We identified a novel frameshift mutation, c.4611_4612insG:p.T1537fs, in exon 49 of COL4A1. This mutation predicts truncation of the protein with disruption of the C-terminal part of the NC1 domain. We confirmed its presence in 20 family members, 17 with confirmed haematuria, 5 of whom also had stage 4 or 5 chronic kidney disease. Eleven family members exhibited kidney cysts (55% of those with the mutation), but muscle cramps or cerebral aneurysms were not observed and serum creatine kinase was normal in all individuals tested. CONCLUSIONS: Missense mutations of COL4A1 that encode the CB3 [IV] segment of the triple helical domain (exons 24 and 25) are associated with HANAC syndrome (hereditary angiopathy, nephropathy, aneurysms and cramps). Missense mutations of COL4A1 that disrupt the NC1 domain are associated with antenatal cerebral haemorrhage and porencephaly, but not kidney disease. Our findings extend the spectrum of COL4A1 mutations linked with renal disease and demonstrate that the highly conserved C-terminal part of the NC1 domain of the α1 chain of type IV collagen is important in the integrity of glomerular basement membrane in humans

Expansion and evaporation of hot nuclei: Comparison between semi-classical and quantal mean-field approaches

We present a general discussion of the mean field dynamics of finite nuclei prepared under extreme conditions of temperature and pressure. We compare the prediction of semi-classical approximation with complete quantum simulations. Many features of the dynamics are carefully studied such as the collective expansion, the evaporation process, the different time-scale... This study points out many quantitative differences between quantum and semi-classical approaches. Part of the differences are related to numerical features inherent in semi-classical simulations but most of them are a direct consequence of the non treatment of nuclei as quantal objects. In particular, we show that because of a too strong damping in semi-classical approaches the expansion of hot nuclei is quenched and the speed of the collective motion reduced.Comment: 41 pages including 14 figure

Hadronic Spectral Functions in Lattice QCD

QCD spectral functions of hadrons in the pseudo-scalar and vector channels are extracted from lattice Monte Carlo data of the imaginary time Green's functions. The maximum entropy method works well for this purpose, and the resonance and continuum structures in the spectra are obtained in addition to the ground state peaks.Comment: 4 pages, 3 eps-figures, revtex (minor modifications in the text and an added reference). To appear in Physical Review D Rapid Communication

Heavy Quark Potentials in Quenched QCD at High Temperature

Heavy quark potentials are investigated at high temperatures. The temperature range covered by the analysis extends from $T$ values just below the deconfinement temperature up to about $4 T_c$ in the deconfined phase. We simulated the pure gauge sector of QCD on lattices with temporal extents of 4, 6 and 8 with spatial volumes of $32^3$. On the smallest lattice a tree level improved action was employed while in the other two cases the standard Wilson action was used. Below $T_c$ we find a temperature dependent logarithmic term contributing to the confinement potential and observe a string tension which decreases with rising temperature but retains a finite value at the deconfinement transition. Above $T_c$ the potential is Debye-screened, however simple perturbative predictions do not apply.Comment: 20 pages, 9 figure

Recurrence of complement factor H-related protein 5 nephropathy in a renal transplant.

Complement factor H-related protein 5 (CFHR5) nephropathy is a familial renal disease endemic in Cyprus. It is characterized by persistent microscopic hematuria, synpharyngitic macroscopic hematuria and progressive renal impairment. Isolated glomerular accumulation of complement component 3 (C3) is typical with variable degrees of glomerular inflammation. Affected individuals have a heterozygous internal duplication in the CFHR5 gene, although the mechanism through which this mutation results in renal disease is not understood. Notably, the risk of progressive renal failure in this condition is higher in males than females. We report the first documented case of recurrence of CFHR5 nephropathy in a renal transplant in a 53-year-old Cypriot male. Strikingly, histological changes of CFHR5 nephropathy were evident in the donor kidney 46 days post-transplantation. This unique case demonstrates that renal-derived CFHR5 protein cannot prevent the development of CFHR5 nephropathy

Isospin Physics in Heavy-Ion Collisions at Intermediate Energies

In nuclear collisions induced by stable or radioactive neutron-rich nuclei a transient state of nuclear matter with an appreciable isospin asymmetry as well as thermal and compressional excitation can be created. This offers the possibility to study the properties of nuclear matter in the region between symmetric nuclear matter and pure neutron matter. In this review, we discuss recent theoretical studies of the equation of state of isospin-asymmetric nuclear matter and its relations to the properties of neutron stars and radioactive nuclei. Chemical and mechanical instabilities as well as the liquid-gas phase transition in asymmetric nuclear matter are investigated. The in-medium nucleon-nucleon cross sections at different isospin states are reviewed as they affect significantly the dynamics of heavy ion collisions induced by radioactive beams. We then discuss an isospin-dependent transport model, which includes different mean-field potentials and cross sections for the proton and neutron, and its application to these reactions. Furthermore, we review the comparisons between theoretical predictions and available experimental data. In particular, we discuss the study of nuclear stopping in terms of isospin equilibration, the dependence of nuclear collective flow and balance energy on the isospin-dependent nuclear equation of state and cross sections, the isospin dependence of total nuclear reaction cross sections, and the role of isospin in preequilibrium nucleon emissions and subthreshold pion production.Comment: 101 pages with embedded epsf figures, review article for "International Journal of Modern Physics E: Nuclear Physics". Send request for a hard copy to 1/author

Cardiovascular, endocrine and behavioural responses to suckling and permanent separation in goats

<p>Abstract</p> <p>Background</p> <p>Suckling can be a peaceful or vulnerable event for goats and kids, whereas, separation is suggested as stressful. The aim of this study was to investigate physiology and behaviour in these two different situations in dairy goats.</p> <p>Methods</p> <p>Four studies were performed with seven goats kept with their first-born kid in individual boxes. The goats were videotaped and heart rate and arterial blood pressure were recorded every minute by telemetry from parturition until 24 hours after separation. One to two days after parturition, Study 1 was performed with analyses of heart rate and blood pressure around a suckling. In Study 2, performed 3-5 days after parturition, blood sampling was done before, during and after suckling. Study 3 was performed 4-6 days post partum, with blood sampling before and after a permanent goat and kid separation. In addition, vocalisations were recorded after separation. Blood samples were obtained from a jugular vein catheter and analysed for plasma cortisol, β-endorphin, oxytocin, and vasopressin concentrations. Study 4 was performed during the first (N1) and second nights (N2) after parturition and the nights after Study 2 (N3) and 3 (N4). Heart rate, blood pressure and time spent lying down were recorded.</p> <p>Results</p> <p>The kids suckled 2 ± 0.2 times per hour and each suckling bout lasted 43 ± 15 s. In Study 1, heart rate and blood pressure did not change significantly during undisturbed suckling. In Study 2, plasma cortisol (P ≤ 0.05 during suckling and P ≤ 0.01 five minutes after suckling) and β-endorphin (P ≤ 0.05) concentrations increased during suckling, but oxytocin and vasopressin concentrations did not change. In Study 3, the goats and kids vocalised intensively during the first 20 minutes after separation, but the physiological variables were not affected. In Study 4, heart rate and arterial blood pressure declined gradually after parturition and were lowest during N4 (P ≤ 0.05) when the goats spent longer time lying down than during earlier nights (P ≤ 0.01 during N1 and N3 and P ≤ 0.05 during N2).</p> <p>Conclusions</p> <p>Suckling elevated plasma cortisol and β-endorphin concentrations in the goats. The intensive vocalisation in the goats after separation, earlier suggested to indicate stress, was not accompanied by cardiovascular or endocrine responses.</p