The thermal QCD transition with two flavours of twisted mass fermions

We investigate the thermal QCD transition with two flavors of maximally twisted mass fermions for a set of pion masses, 300 MeV \textless $m_\pi$ \textless 500 MeV, and lattice spacings $a$ \textless 0.09 fm. We determine the pseudo-critical temperatures and discuss their extrapolation to the chiral limit using scaling forms for different universality classes, as well as the scaling form for the magnetic equation of state. For all pion masses considered we find resonable consistency with O(4) scaling plus leading corrections. However, a true distinction between the O(4) scenario and a first order scenario in the chiral limit requires lighter pions than are currently in use in simulations of Wilson fermions.Comment: 11 pages, 11 figure

Computational approaches to shed light on molecular mechanisms in biological processes

Computational approaches based on Molecular Dynamics simulations, Quantum Mechanical methods and 3D Quantitative Structure-Activity Relationships were employed by computational chemistry groups at the University of Milano-Bicocca to study biological processes at the molecular level. The paper reports the methodologies adopted and the results obtained on Aryl hydrocarbon Receptor and homologous PAS proteins mechanisms, the properties of prion protein peptides, the reaction pathway of hydrogenase and peroxidase enzymes and the defibrillogenic activity of tetracyclines. © Springer-Verlag 2007

Differential allelic expression of SOS1 and hyperexpression of the activating SOS1 c.755C variant in a Noonan syndrome family

Noonan syndrome (NS) is a genetic condition characterized by congenital heart defects, short stature and characteristic facial features. We here present the case of a girl with moderate learning disabilities, delayed language development, craniofacial features and skin anomalies reminiscent of NS. After a mutation screening of the known NS genes PTPN11, SOS1, RAF1, KRAS, GRB2, BRAF and SHOC2 we found the heterozygous c.755T>C variant in SOS1 causing the p.I252T amino-acid substitution, which was considered possibly pathogenetic by bioinformatic predictions. The same variant was present in the proband's mother, displaying some NS features, and mateRNAl grandfather showing no NS traits, but also by a healthy subject in 1000 genomes project database without phenotype informations. The functional analysis revealed that SOS1 c.755C activated the RAS-ERK intracellular pathway, whereas no effects on RAC-JNK cascade have been detected. After a comparison between the sequence of SOS1 cDNA from peripheral blood and SOS1 genomic DNA, we showed for the first time a differential allelic expression of the SOS1 gene in healthy individuals, thus occurring as a physiologic condition. Interestingly, we found that the mutated allele C was 50% more expressed than the wild-type allele T in all familial carriers. The comparable amount of SOS1 mRNA between mutated individuals and the controls indicates that the variant does not affect SOS1 expression. The present study provides a first evidence of allelic imbalance of SOS1 and pinpoints this condition as a possible mechanism underlying a different penetrance of some SOS1-mutated alleles in unrelated carriers

9q34.3 microduplications lead to neurodevelopmental disorders through EHMT1 overexpression

Both copy number losses and gains occur within subtelomeric 9q34 region without common breakpoints. The microdeletions cause Kleefstra syndrome (KS), whose responsible gene is EHMT1. A 9q34 duplication syndrome (9q34 DS) had been reported in literature, but it has never been characterized by a detailed molecular analysis of the gene content and endpoints. To the best of our knowledge, we report on the first patient carrying the smallest 9q34.3 duplication containing EHMT1 as the only relevant gene. We compared him with 21 reported patients described here as carrying 9q34.3 duplications encompassing the entire gene and extending within ~\u20093 Mb. By surveying the available clinical and molecular cytogenetic data, we were able to discover that similar neurodevelopmental disorders (NDDs) were shared by patient carriers of even very differently sized duplications. Moreover, some facial features of the 9q34 DS were more represented than those of KS. However, an accurate in silico analysis of the genes mapped in all the duplications allowed us to support EHMT1 as being sufficient to cause a NDD phenotype. Wider patient cohorts are needed to ascertain whether the rearrangements have full causative role or simply confer the susceptibility to NDDs and possibly to identify the cognitive and behavioral profile associated with the increased dosage of EHMT1

Gout and kidney during XVII and XIX centuries

The authors briefly describe the history of gout, mainly focusing their attention on the renal involvement. They report some works and theories on gout of great ancient physicians, such as Paracelsus, Sydenham, Boerhaave, Van Swieten and Morgagni

PT-symmetry breaking in complex nonlinear wave equations and their deformations

We investigate complex versions of the Korteweg-deVries equations and an Ito type nonlinear system with two coupled nonlinear fields. We systematically construct rational, trigonometric/hyperbolic, elliptic and soliton solutions for these models and focus in particular on physically feasible systems, that is those with real energies. The reality of the energy is usually attributed to different realisations of an antilinear symmetry, as for instance PT-symmetry. It is shown that the symmetry can be spontaneously broken in two alternative ways either by specific choices of the domain or by manipulating the parameters in the solutions of the model, thus leading to complex energies. Surprisingly the reality of the energies can be regained in some cases by a further breaking of the symmetry on the level of the Hamiltonian. In many examples some of the fixed points in the complex solution for the field undergo a Hopf bifurcation in the PT-symmetry breaking process. By employing several different variants of the symmetries we propose many classes of new invariant extensions of these models and study their properties. The reduction of some of these models yields complex quantum mechanical models previously studied.Comment: 50 pages, 39 figures (compressed in order to comply with arXiv policy; higher resolutions maybe obtained from the authors upon request

Magnetothermodynamics of BPS baby skyrmions

The magnetothermodynamics of skyrmion type matter described by the gauged BPS baby Skyrme model at zero temperature is investigated. We prove that the BPS property of the model is preserved also for boundary conditions corresponding to an asymptotically constant magnetic field. The BPS bound and the corresponding BPS equations saturating the bound are found. Further, we show that one may introduce pressure in the gauged model by a redefinition of the superpotential. Interestingly, this is related to non-extremal type solutions in the so-called fake supersymmetry method. Finally, we compute the equation of state of magnetized BSP baby skyrmions inserted into an external constant magnetic field $H$ and under external pressure $P$, i.e., $V=V(P,H)$, where $V$ is the "volume" (area) occupied by the skyrmions. We show that the BPS baby skyrmions form a ferromagnetic medium.Comment: Latex, 39 pages, 14 figures. v2: New results and references added, physical interpretation partly change

Novel mutations in the CDKL5 gene, predicted effects and associated phenotypes

It has been found that CDKL5 gene mutations are responsible for early-onset epilepsy and drug resistance. We screened a population of 92 patients with classic/atypical Rett syndrome, 17 Angelman/Angelman-like patients and six idiopathic autistic patients for CDKL5 mutations and exon deletions and identified seven novel mutations: six in the Rett subset and one in an Angelman patient. This last, an insertion in exon 11, c.903_904 dupGA, p.Leu302Aspfx49X, is associated with a relatively mild clinical presentation as the patient is the only one capable of sitting and walking alone. Of the six mutations, two are de novo missense changes affecting highly conserved aminoacid residues, c.215 T > C p.Ile72Thr and c.380A > G p.His127Arg (present in a mosaic condition) found in two girls with the most severe clinical presentation, while the remaining are the splicing c.145 + 2 T > C and c.2376 + 5G > A, the c.1648C > T p.Arg550X and the MPLA-identified c.162_99del261 mutation. RNA characterisation of four mutations revealed the aberrant transcript of the missense allele (case 2) and not the stop mutation (case 3), but also allowed the splicing mutation (case 1) and the c.-162_99del261 (case 4) to be ategorised as truncating. The obtained data reinforce the view that a more severe phenotype is due more to an altered protein than haploinsufficiency. Furthermore, the mutational repertoire of the CDKL5 gene is shown to be expanded by testing patients with phenotypical overlap to Rett syndrome and applying multiplex ligation-dependent probe amplification

Comparative analysis of homology models of the Ah receptor ligand binding domain: Verification of structure-function predictions by site-directed mutagenesis of a nonfunctional receptor

The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that mediates the biological and toxic effects of a wide variety of structurally diverse chemicals, including the toxic environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). While significant interspecies differences in AHR ligand binding specificity, selectivity, and response have been observed, the structural determinants responsible for those differences have not been determined, and homology models of the AHR ligand-binding domain (LBD) are available for only a few species. Here we describe the development and comparative analysis of homology models of the LBD of 16 AHRs from 12 mammalian and nonmammalian species and identify the specific residues contained within their ligand binding cavities. The ligand-binding cavity of the fish AHR exhibits differences from those of mammalian and avian AHRs, suggesting a slightly different TCDD binding mode. Comparison of the internal cavity in the LBD model of zebrafish (zf) AHR2, which binds TCDD with high affinity, to that of zfAHR1a, which does not bind TCDD, revealed that the latter has a dramatically shortened binding cavity due to the side chains of three residues (Tyr296, Thr386, and His388) that reduce the amount of internal space available to TCDD. Mutagenesis of two of these residues in zfAHR1a to those present in zfAHR2 (Y296H and T386A) restored the ability of zfAHR1a to bind TCDD and to exhibit TCDD-dependent binding to DNA. These results demonstrate the importance of these two amino acids and highlight the predictive potential of comparative analysis of homology models from diverse species. The availability of these AHR LBD homology models will facilitate in-depth comparative studies of AHR ligand binding and ligand-dependent AHR activation and provide a novel avenue for examining species-specific differences in AHR responsiveness. © 2013 American Chemical Society