Charmed states and flavour symmetry breaking

Extending the SU(3) flavour symmetry breaking expansion from up, down and strange sea quark masses to partially quenched valence quark masses allows an extrapolation to the charm quark mass. This approach leads to a determination of charmed quark hadron masses and decay constants. We describe our recent progress and give preliminary results in particular with regard to the recently discovered doubly charmed baryon by the LHCb Collaboration.Comment: 8 pages, 9 figures, talk presented at the 35th International Symposium on Lattice Field Theory, 18-24 June 2017, Granada, Spai

Genotyping of black grouse MHC class II B using reference Strand-Mediated Conformational Analysis (RSCA)

<p>Abstract</p> <p>Background</p> <p>The Major Histocompatibility Complex (MHC) is a cluster of genes involved in the vertebrate immune system and includes loci with an extraordinary number of alleles. Due to the complex evolution of MHC genes, alleles from different loci within the same MHC class can be very similar and therefore difficult to assign to separate loci. Consequently, single locus amplification of MHC genes is hard to carry out in species with recently duplicated genes in the same MHC class, and multiple MHC loci have to be genotyped simultaneously. Since amplified alleles have the same length, accurate genotyping is difficult. Reference Strand-Mediated Conformational Analysis (RSCA), which is increasingly used in studies of natural populations with multiple MHC genes, is a genotyping method capable to provide high resolution and accuracy in such cases.</p> <p>Findings</p> <p>We adapted the RSCA method to genotype multiple MHC class II B (BLB) genes in black grouse (<it>Tetrao tetrix</it>), a non-model galliform bird species, using a 96-Capillary Array Electrophoresis, the MegaBACE™ 1000 DNA Analysing System (GE Healthcare). In this study we used fluorescently labelled reference strands from both black grouse and hazel grouse and observed good agreement between RSCA and cloning/sequencing since 71 alleles were observed by cloning/sequencing and 76 alleles by RSCA among the 24 individuals included in the comparison. At the individual level however, there was a trend towards more alleles scored with RSCA (1-6 per individual) than cloning/sequencing (1-4 per individual). In 63% of the pair-wise comparison, the identical allele was scored in RSCA as in cloning/sequencing. Nine out of 24 individuals had the same number of alleles in RSCA as in cloning/sequencing. Our RSCA protocol allows a faster RSCA genotyping than presented in many other RSCA studies.</p> <p>Conclusions</p> <p>In this study, we have developed the RSCA typing method further to work on a 96-Capillary Array Electrophoresis (MegaBACE™ 1000). Our RSCA protocol can be applied to fast and reliable screening of MHC class II B diversity of black grouse populations. This will facilitate future large-scale population studies of black grouse and other galliformes species with multiple inseparable MHC loci.</p

Characterisation of the anti-apoptotic function of survivin-ΔEx3 during TNFα−mediated cell death

Survivin is an oncogenic protein involved in cell division and acts as an anti-apoptotic factor. It is highly expressed in most cancers and is associated with chemotherapy resistance, increased tumour recurrence, and shorter patient survival. This makes anti-survivin therapy an attractive cancer treatment strategy. These functions are mediated by several survivin spliced variants, whose expression may correlate with cancer progression. One of the spliced variants, survivin-ΔEx3, is known to inhibit apoptosis, through undefined mechanisms. Here, we characterised these mechanisms upon TNFα−mediated apoptosis, and showed that survivin-ΔEx3 acts as an adaptor, allowing the formation of a complex between Bcl-2 and activated caspase-3. The Bcl-2/survivin-ΔEx3 complex, but not survivin-ΔEx3 itself, inhibits the activity of caspase-3. Bcl-2 is therefore linked to the postmitochondrial apoptotic machinery by survivin-ΔEx3. Thus, survivin-ΔEx3 plays a key role in the inhibition of caspase-3 activity, and in the control of the mitochondrial checkpoint of apoptosis. This study suggests that targeting survivin-ΔEx3, rather than survivin alone, could be relevant for treating human cancers

In silico assessment of the effects of quinidine, disopyramide and E-4031 on short QT syndrome variant 1 in the human ventricles.

Aims Short QT syndrome (SQTS) is an inherited disorder associated with abnormally abbreviated QT intervals and an increased incidence of atrial and ventricular arrhythmias. SQT1 variant (linked to the rapid delayed rectifier potassium channel current, IKr) of SQTS, results from an inactivation-attenuated, gain-of-function mutation (N588K) in the KCNH2-encoded potassium channels. Pro-arrhythmogenic effects of SQT1 have been well characterized, but less is known about the possible pharmacological antiarrhythmic treatment of SQT1. Therefore, this study aimed to assess the potential effects of E-4031, disopyramide and quinidine on SQT1 using a mathematical model of human ventricular electrophysiology. Methods The ten Tusscher et al. biophysically detailed model of the human ventricular action potential (AP) was modified to incorporate IKr Markov chain (MC) formulations based on experimental data of the kinetics of the N588K mutation of the KCNH2-encoded subunit of the IKr channels. The modified ventricular cell model was then integrated into one-dimensional (1D) strand, 2D regular and realistic tissues with transmural heterogeneities. The channel-blocking effect of the drugs on ion currents in healthy and SQT1 cells was modeled using half-maximal inhibitory concentration (IC50) and Hill coefficient (nH) values from literatures. Effects of drugs on cell AP duration (APD), effective refractory period (ERP) and pseudo-ECG traces were calculated. Effects of drugs on the ventricular temporal and spatial vulnerability to re-entrant excitation waves were measured. Re-entry was simulated in both 2D regular and realistic ventricular tissue. Results At the single cell level, the drugs E-4031 and disopyramide had hardly noticeable effects on the ventricular cell APD at 90% repolarization (APD90), whereas quinidine caused a significant prolongation of APD90. Quinidine prolonged and decreased the maximal transmural AP heterogeneity (δV); this led to the decreased transmural heterogeneity of APD across the 1D strand. Quinidine caused QT prolongation and a decrease in the T-wave amplitude, and increased ERP and decreased temporal susceptibility of the tissue to the initiation of re-entry and increased the minimum substrate size necessary to prevent re-entry in the 2D regular model, and further terminated re-entrant waves in the 2D realistic model. Quinidine exhibited significantly better therapeutic effects on SQT1 than E-4031 and disopyramide. Conclusions The simulated pharmacological actions of quinidine exhibited antiarrhythmic effects on SQT1. This study substantiates a causal link between quinidine and QT interval prolongation in SQT1 and suggests that quinidine may be a potential pharmacological agent for treating SQT1 patients

Portland Daily Press: May 10,1883

https://digitalmaine.com/pdp_1883/1093/thumbnail.jp

Late-Night Overeating or Low-Quality Food Choices Late at Night Are Associated with Subclinical Vascular Damage in Patients at Increased Cardiovascular Risk

Late-night overeating (LNO) is associated with several cardiovascular disease (CVD) risk factors. Limited data exist regarding the association between late-night (LN) systematic food consumption, LNO, and LN poor food quality with subclinical vascular damage (SVD) which precedes the onset of CVD. This study aimed to investigate the above associations with SVD in a large sample of adults, free of established CVD, with one or more CVD risk factors. In total, 901 adults (45.2% males) underwent anthropometric, dietary (through two 24 h dietary recalls) and vascular assessment. LN systematic eating was defined as consumption of food after 19:00 h in both dietary recalls and LNO was defined as systematic consumption of >40% of daily total energy intake (dTEI) after 19:00 h. Systematic LN food consumption was inversely associated with diastolic blood pressure (DBP) (−1.44 95% C.I. (−2.76, −0.12)) after adjusting for age, sex, hypertension, diabetes, dyslipidemia, smoking, BMI and dTEI. LNO was positively associated with existence of carotid plaques (1.70 95% C.I. (1.07, 2.68)), while LN increased consumption of red meat, refined grains and wine and low consumption of whole wheat grains was positively associated with Aix (Augmentation Index) (0.84 95% C.I. (0.09, 1.59)), after adjusting for all the mentioned confounders. Systematic LN eating is associated with lower DBP while systematic LNO and consumption of poor-quality food late at night, is associated with SVD. Further research is needed to define more accurately the impact of LN eating habits on vascular health

State mixing and masses of the π0\pi^0, η\eta and η′\eta^\prime mesons from nf=1+1+1n_f=1+1+1 lattice QCD+QED

We present a lattice analysis of the light pseudoscalar mesons with consideration for the mixing between the flavour-neutral states $\pi^0$, $\eta$ and $\eta^\prime$. We extract the masses and flavour compositions of the pseudoscalar meson nonet in $n_f=1+1+1$ lattice QCD+QED around an SU(3)-flavour symmetric point, and observe flavour-symmetry features of the extracted data, along with preliminary extrapolation results for the flavour compositions at physical pion mass via a novel method. A key result of this work is the observed mass splitting between the $\pi^0$ and $\eta$ on our ensembles, which is found to exhibit behaviour that is simply related to the corresponding flavour compositions

State mixing and masses of the pi(0), eta and eta ' mesons from n(f)=1+1+1 lattice QCD plus QED

We present a lattice analysis of the light pseudoscalar mesons with consideration for the mixing between the flavour-neutral states $\pi^0$, $\eta$ and $\eta^\prime$. We extract the masses and flavour compositions of the pseudoscalar meson nonet in $n_f=1+1+1$ lattice QCD+QED around an SU(3)-flavour symmetric point, and observe flavour-symmetry features of the extracted data, along with preliminary extrapolation results for the flavour compositions at the physical point. A key result of this work is the observed mass splitting between the $\pi^0$ and $\eta$ on our ensembles, which is found to exhibit behaviour that is simply related to the corresponding flavour compositions.Comment: 9 pages, 4 figures. Some small changes and added discussion. Version to appear in PR