Remarkable Ancient Divergences Amongst Neglected Lorisiform Primates

Lorisiform primates (Primates: Strepsirrhini: Lorisiformes) represent almost 10% of the living primate species and are widely distributed in sub-Saharan Africa and South/South-East Asia; however, their taxonomy, evolutionary history, and biogeography are still poorly understood. In this study we report the largest molecular phylogeny in terms of the number of represented taxa. We sequenced the complete mitochondrial cytochrome b gene for 86 lorisiform specimens, including ∼80% of all the species currently recognized. Our results support the monophyly of the Galagidae, but a common ancestry of the Lorisinae and Perodicticinae (family Lorisidae) was not recovered. These three lineages have early origins, with the Galagidae and the Lorisinae diverging in the Oligocene at about 30 Mya and the Perodicticinae emerging in the early Miocene. Our mitochondrial phylogeny agrees with recent studies based on nuclear data, and supports Euoticus as the oldest galagid lineage and the polyphyletic status of Galagoides. Moreover, we have elucidated phylogenetic relationships for several species never included before in a molecular phylogeny. The results obtained in this study suggest that lorisiform diversity remains substantially underestimated and that previously unnoticed cryptic diversity might be present within many lineages, thus urgently requiring a comprehensive taxonomic revision of this primate group

Attenuated PDGF signaling drives alveolar and microvascular defects in neonatal chronic lung disease

Neonatal chronic lung disease (nCLD) affects a significant number of neonates receiving mechanical ventilation with oxygen-rich gas (MV-O2). Regardless, the primary molecular driver of the disease remains elusive. We discover significant enrichment for SNPs in the PDGF-Rα gene in preterms with nCLD and directly test the effect of PDGF-Rα haploinsufficiency on the development of nCLD using a preclinical mouse model of MV-O2. In the context of MV-O2, attenuated PDGF signal

Study of J/ψ→ppˉJ/\psi\to p\bar{p} and J/ψ→nnˉJ/\psi\to n\bar{n}

The decays $J/\psi\to p\bar{p}$ and $J/\psi\to n\bar{n}$ have been investigated with a sample of 225.2 million $J/\psi$ events collected with the BESIII detector at the BEPCII $e^+e^-$ collider. The branching fractions are determined to be $\mathcal{B}(J/\psi\to p\bar{p})=(2.112\pm0.004\pm0.031)\times10^{-3}$ and $\mathcal{B}(J/\psi\to n\bar{n})=(2.07\pm0.01\pm0.17)\times10^{-3}$. Distributions of the angle $\theta$ between the proton or anti-neutron and the beam direction are well described by the form $1+\alpha\cos^2\theta$, and we find $\alpha=0.595\pm0.012\pm0.015$ for $J/\psi\to p\bar{p}$ and $\alpha=0.50\pm0.04\pm0.21$ for $J/\psi\to n\bar{n}$. Our branching-fraction results suggest a large phase angle between the strong and electromagnetic amplitudes describing the $J/\psi\to N\bar{N}$ decay.Comment: 16 pages, 13 figures, the 2nd version, submitted to PR

First observation of the M1 transition ψ(3686)→γηc(2S)\psi(3686)\to \gamma\eta_c(2S)

Using a sample of 106 million \psi(3686) events collected with the BESIII detector at the BEPCII storage ring, we have made the first measurement of the M1 transition between the radially excited charmonium S-wave spin-triplet and the radially excited S-wave spin-singlet states: \psi(3686)\to\gamma\eta_c(2S). Analyses of the processes \psi(2S)\to \gamma\eta_c(2S) with \eta_c(2S)\to \K_S^0 K\pi and K^+K^-\pi^0 gave an \eta_c(2S) signal with a statistical significance of greater than 10 standard deviations under a wide range of assumptions about the signal and background properties. The data are used to obtain measurements of the \eta_c(2S) mass (M(\eta_c(2S))=3637.6\pm 2.9_\mathrm{stat}\pm 1.6_\mathrm{sys} MeV/c^2), width (\Gamma(\eta_c(2S))=16.9\pm 6.4_\mathrm{stat}\pm 4.8_\mathrm{sys} MeV), and the product branching fraction (\BR(\psi(3686)\to \gamma\eta_c(2S))\times \BR(\eta_c(2S)\to K\bar K\pi) = (1.30\pm 0.20_\mathrm{stat}\pm 0.30_\mathrm{sys})\times 10^{-5}). Combining our result with a BaBar measurement of \BR(\eta_c(2S)\to K\bar K \pi), we find the branching fraction of the M1 transition to be \BR(\psi(3686)\to\gamma\eta_c(2S)) = (6.8\pm 1.1_\mathrm{stat}\pm 4.5_\mathrm{sys})\times 10^{-4}.Comment: 7 pages, 1 figure, 1 tabl

Two-photon widths of the χc0,2\chi_{c0, 2} states and helicity analysis for \chi_{c2}\ar\gamma\gamma}

Based on a data sample of 106 M $\psi^{\prime}$ events collected with the BESIII detector, the decays \psi^{\prime}\ar\gamma\chi_{c0, 2},\chi_{c0, 2}\ar\gamma\gamma are studied to determine the two-photon widths of the $\chi_{c0, 2}$ states. The two-photon decay branching fractions are determined to be {\cal B}(\chi_{c0}\ar\gamma\gamma) = (2.24\pm 0.19\pm 0.12\pm 0.08)\times 10^{-4} and {\cal B}(\chi_{c2}\ar\gamma\gamma) = (3.21\pm 0.18\pm 0.17\pm 0.13)\times 10^{-4}. From these, the two-photon widths are determined to be $\Gamma_{\gamma \gamma}(\chi_{c0}) = (2.33\pm0.20\pm0.13\pm0.17)$ keV, $\Gamma_{\gamma \gamma}(\chi_{c2}) = (0.63\pm0.04\pm0.04\pm0.04)$ keV, and $\cal R$ $=\Gamma_{\gamma \gamma}(\chi_{c2})/\Gamma_{\gamma \gamma}(\chi_{c0})=0.271\pm 0.029\pm 0.013\pm 0.027$, where the uncertainties are statistical, systematic, and those from the PDG {\cal B}(\psi^{\prime}\ar\gamma\chi_{c0,2}) and $\Gamma(\chi_{c0,2})$ errors, respectively. The ratio of the two-photon widths for helicity $\lambda=0$ and helicity $\lambda=2$ components in the decay \chi_{c2}\ar\gamma\gamma is measured for the first time to be $f_{0/2} =\Gamma^{\lambda=0}_{\gamma\gamma}(\chi_{c2})/\Gamma^{\lambda=2}_{\gamma\gamma}(\chi_{c2}) = 0.00\pm0.02\pm0.02$.Comment: 10 pages, 4 figure

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Probing the bradycardic drug binding receptor of HCN-encoded pacemaker channels

If (or Ih), encoded by the hyperpolarization-activated, cyclic nucleotide-gated (HCN1–4) channel gene family, contributes significantly to cardiac pacing. Bradycardic agents such as ZD7288 that target HCN channels have been developed, but the molecular configuration of their receptor is poorly defined. Here, we probed the drug receptor by systematically introducing alanine scanning substitutions into the selectivity filter (C347A, I348A, G349A, Y350A, G351A in the P-loop), outer (P355A, V356A, S357A, M358A in the P-S6 linker), and inner (M377A, F378A, V379A in S6) pore vestibules of HCN1 channels. When heterologously expressed in human embryonic kidney 293 cells for patch-clamp recordings, I348A, G349A, Y350A, G351A, P355A, and V356A did not produce measurable currents. The half-blocking concentration (IC50) of wild type (WT) for ZD7288 was 25.8 ± 9.7 μM. While the IC50 of M358A was identical to WT, those of C347A, S357A, F378A, and V379A markedly increased to 137.6 ± 56.4, 113.3 ± 34.1, 587.1 ± 167.5, and 1726.3 ± 673.4 μM, respectively (p < 0.05). Despite the proximity of the S6 residues studied, M377A was hypersensitive (IC50 = 5.1 ± 0.7 μM; p < 0.05) implicating site specificity. To explore the energetic interactions among the S6 residues, double and triple substitutions (M377A/F378A, M377A/V379A, F378A/V379A, and M377A/F378A/V379A) were generated for thermodynamic cycle analysis. Specific interactions with coupling energies (ΔΔG) >1 kT for M377–F378 and F378–V379 but not M377–V379 were identified. Based on these new data and others, we proposed a refined drug-blocking model that may lead to improved antiarrhythmics and bioartificial pacemaker designs