Chondrodysplasia-Like Dwarfism in the Miniature Horse

Dwarfism is considered one of the most recognized congenital defects of animals and humans and can be hereditary or sporadic in cause and expression. There are two general morphologic categories within this vastly diverse disease. These categories are disproportionate and proportionate dwarfism and within each of these there are numerous phenotypes which have been extensively described in humans, and to a lesser extent in dogs, cattle, mice, chickens, and other domestic species. Ponies and Miniature horses largely differ from full size horses only by their stature. Ponies are often defined as those whose height is not greater than 14.2 hands; however the maximum height for Miniature horses is constitutionally defined as 8.2 hands. Dwarfism is not considered a desirable genetic trait for Miniature horses. A majority of these conformationally inferior horses showed consistent physical abnormalities typical of disproportionate dwarfisms as seen in other mammal species. A whole genome scan with the Illumina Equine SNP50 chip clearly implicated a region on ECA1 as being associated with dwarfism of horses. The region implicated on the horse chromosome 1 (Equus Caballus; ECA1) contained a candidate gene for dwarfism, aggrecan (ACAN). Mutations were found in Exons 2, 6, 11 and 15 with each mutation associated with a distinct type of dwarfism. These mutations are independently transmitted throughout the population. Absence of normal homozygotes for these mutations and absence of normal horses which were heterozygous for these mutations indicated that these alleles caused dwarfism in those genotypes. These genotypes did not explain all observed dwarves in this population

Equine Arteritis Virus Uses Equine CXCL16 as an Entry Receptor

Previous studies in our laboratory have identified equine CXCL16 (EqCXCL16) to be a candidate molecule and possible cell entry receptor for equine arteritis virus (EAV). In horses, the CXCL16 gene is located on equine chromosome 11 (ECA11) and encodes a glycosylated, type I transmembrane protein with 247 amino acids. Stable transfection of HEK-293T cells with plasmid DNA carrying EqCXCL16 (HEK-EqCXCL16 cells) increased the proportion of the cell population permissive to EAV infection from \u3c 3% to almost 100%. The increase in permissiveness was blocked either by transfection of HEK-EqCXCL16 cells with small interfering RNAs (siRNAs) directed against EqCXCL16 or by pretreatment with guinea pig polyclonal antibody against EqCXCL16 protein (Gp anti-EqCXCL16 pAb). Furthermore, using a virus overlay protein-binding assay (VOPBA) in combination with far-Western blotting, gradient-purified EAV particles were shown to bind directly to the EqCXCL16 protein in vitro. The binding of biotinylated virulent EAV strain Bucyrus at 4°C was significantly higher in HEK-EqCXCL16 cells than nontransfected HEK-293T cells. Finally, the results demonstrated that EAV preferentially infects subpopulations of horse CD14+ monocytes expressing EqCXCL16 and that infection of these cells is significantly reduced by pretreatment with Gp anti-EqCXCL16 pAb. The collective data from this study provide confirmatory evidence that the transmembrane form of EqCXCL16 likely plays a major role in EAV host cell entry processes, possibly acting as a primary receptor molecule for this virus

Allelic Variation in \u3cem\u3eCXCL16\u3c/em\u3e Determines CD3\u3csup\u3e+\u3c/sup\u3e T Lymphocyte Susceptibility to Equine Arteritis Virus Infection and Establishment of Long-Term Carrier State in the Stallion

Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA), a respiratory, systemic, and reproductive disease of horses and other equid species. Following natural infection, 10–70% of the infected stallions can become persistently infected and continue to shed EAV in their semen for periods ranging from several months to life. Recently, we reported that some stallions possess a subpopulation(s) of CD3+ T lymphocytes that are susceptible to in vitro EAV infection and that this phenotypic trait is associated with long-term carrier status following exposure to the virus. In contrast, stallions not possessing the CD3+ T lymphocyte susceptible phenotype are at less risk of becoming long-term virus carriers. A genome wide association study (GWAS) using the Illumina Equine SNP50 chip revealed that the ability of EAV to infect CD3+ T lymphocytes and establish long-term carrier status in stallions correlated with a region within equine chromosome 11. Here we identified the gene and mutations responsible for these phenotypes. Specifically, the work implicated three allelic variants of the equine orthologue of CXCL16 (EqCXCL16) that differ by four non-synonymous nucleotide substitutions (XM_00154756; c.715 A → T, c.801 G → C, c.804 T → A/G, c.810 G → A) within exon 1. This resulted in four amino acid changes with EqCXCL16S (XP_001504806.1) having Phe, His, Ile and Lys as compared to EqCXL16R having Tyr, Asp, Phe, and Glu at 40, 49, 50, and 52, respectively. Two alleles (EqCXCL16Sa, EqCXCL16Sb) encoded identical protein products that correlated strongly with long-term EAV persistence in stallions (P \u3c 0.000001) and are required for in vitro CD3+ T lymphocyte susceptibility to EAV infection. The third (EqCXCL16R) was associated with in vitro CD3+ T lymphocyte resistance to EAV infection and a significantly lower probability for establishment of the long-term carrier state (viral persistence) in the male reproductive tract. EqCXCL16Sa and EqCXCL16Sb exert a dominant mode of inheritance. Most importantly, the protein isoform EqCXCL16S but not EqCXCL16R can function as an EAV cellular receptor. Although both molecules have equal chemoattractant potential, EqCXCL16S has significantly higher scavenger receptor and adhesion properties compared to EqCXCL16R

Identification of high-spin proton configurations in Ba 136 and Ba 137

19 pags., 11 figs., 3 tabs.The high-spin structures of Ba136 and Ba137 are investigated after multinucleon-transfer (MNT) and fusion-evaporation reactions. Ba136 is populated in a Xe136+U238 MNT reaction employing the high-resolution Advanced GAmma Tracking Array (AGATA) coupled to the magnetic spectrometer PRISMA at the Laboratori Nazionali di Legnaro, Italy, and in two Be9+Te130 fusion-evaporation reactions using the High-efficiency Observatory for γ-Ray Unique Spectroscopy (HORUS) at the FN tandem accelerator of the University of Cologne, Germany. Furthermore, both isotopes are populated in an elusive reaction channel in the B11+Te130 fusion-evaporation reaction utilizing the HORUS γ-ray array. The level scheme above the Jπ=10+ isomer in Ba136 is revised and extended up to an excitation energy of approximately 5.5 MeV. From the results of angular-correlation measurements, the Ex=3707- and Ex=4920-keV states are identified as the bandheads of positive- and negative-parity cascades. While the high-spin regimes of both Te132 and Xe134 are characterized by high-energy 12+→10+ transitions, the Ba136E2 ground-state band is interrupted by negative-parity states only a few hundred keV above the Jπ=10+ isomer. Furthermore, spins are established for several hitherto unassigned high-spin states in Ba137. The new results close a gap along the high-spin structure of N<82 Ba isotopes. Experimental results are compared to large-scale shell-model calculations employing the GCN50:82, Realistic SM, PQM130, and SN100PN interactions. The calculations suggest that the bandheads of the positive-parity bands in both isotopes are predominantly of proton character.Furthermore, we express our thanks to Dr. E. Teruya and Dr. N. Yoshinaga from Saitama University, Japan, for providing the results of their shellmodel calculation with the PQM130 interaction. The research leading to these results has received funding from the German BMBF under Contracts No. 05P15PKFN9 TP1 and No. 05P18PKFN9 TP1, from the European Union Seventh Framework Programme FP7/2007-2013 under Grant Agreement No. 262010 - ENSAR, from the Spanish Ministerio de Ciencia e Innovación under Contract No. FPA2011-29854- C04, from the Spanish Ministerio de Economía y Competitividad under Contract No. FPA2014-57196-C5, and from the UK Science and Technology Facilities Council (STFC). L.K. and A.V. thank the Bonn-Cologne Graduate School of Physics and Astronomy (BCGS) for financial support. One of the authors (A. Gadea) has been supported by the Generalitat Valenciana, Spain, under Grant No. PROMETEOII/2014/019, and EU under the FEDER program

Isospin dependence of electromagnetic transition strengths among an isobaric triplet

Electric quadrupole matrix elements, M, for the J=2→0, ΔT=0, T=1 transitions across the A=46 isobaric multiplet Cr-V-Ti have been measured at GSI with the FRS-LYCCA-AGATA setup. This allows direct insight into the isospin purity of the states of interest by testing the linearity of M with respect to T. Pairs of nuclei in the T=1 triplet were studied using identical reaction mechanisms in order to control systematic errors. The M values were obtained with two different methodologies: (i) a relativistic Coulomb excitation experiment was performed for Cr and Ti; (ii) a “stretched target” technique was adopted here, for the first time, for lifetime measurements in V and Ti. A constant value of M across the triplet has been observed. Shell-model calculations performed within the fp shell fail to reproduce this unexpected trend, pointing towards the need of a wider valence space. This result is confirmed by the good agreement with experimental data achieved with an interaction which allows excitations from the underlying sd shell. A test of the linearity rule for all published data on complete T=1 isospin triplets is presented.Peer Reviewe

Shape evolution in the neutron-rich osmium isotopes:Prompt γ-ray spectroscopy of Os 196

The shape transition in the neutron-rich Os isotopes is studied by investigating the neutron-rich 196Os nucleus through in-beam γ-ray spectroscopy using a two-proton transfer reaction from a 198Pt target to a 82Se beam. The beam-like recoils were detected and identified with the large-acceptance magnetic spectrometer PRISMA, and the coincident γ rays were measured with the advanced gamma tracking array (AGATA) demonstrator. The de-excitation of the low-lying levels of the yrast-band of 196Os were identified for the first time. The results are compared with state-of-the-art beyond-mean-field calculations, performed for the even-even 188-198Os isotopes. The new results suggest a smooth transition in the Os isotopes from a more axial rotational behavior towards predominately vibrational nuclei through triaxial configurations. An almost perfect γ-unstable/triaxial rotor yrast band is predicted for 196Os which is in agreement with the experimentally measured excited state

High-spin structures in Xe 132 and Xe 133 and evidence for isomers along the N=79 isotones

The transitional nuclei Xe132 and Xe133 are investigated after multinucleon-transfer (MNT) and fusion-evaporation reactions. Both nuclei are populated (i) in Xe136+Pb208 MNT reactions employing the high-resolution Advanced GAmma Tracking Array (AGATA) coupled to the magnetic spectrometer PRISMA, (ii) in the Xe136+Pt198 MNT reaction employing the GAMMASPHERE spectrometer in combination with the gas-detector array CHICO, and (iii) as an evaporation residue after a Te130(α,xn)Xe134-xn fusion-evaporation reaction employing the HORUS γ-ray array at the University of Cologne. The high-spin level schemes are considerably extended above the Jπ=(7-) and (10+) isomers in Xe132 and above the 11/2- isomer in Xe133. The results are compared to the high-spin systematics of the Z=54 as well as the N=78 and N=79 chains. Furthermore, evidence is found for a long-lived (T1/2â‰1μs) isomer in Xe133 which closes a gap along the N=79 isotones. Shell-model calculations employing the SN100PN and PQM130 effective interactions reproduce the experimental findings and provide guidance to the interpretation of the observed high-spin features