A Heterozygous Missense Variant in MAP2K2 in a Stillborn Romagnola Calf with Skeletal-Cardio-Enteric Dysplasia

RASopathies are a group of developmental disorders caused by dominant mutations in genes that encode components of the Ras/mitogen-activated protein kinase (MAPK) cell signaling pathway. The goal of this study was to characterize the pathological phenotype of a Romagnola stillborn calf with skeletal-cardio-enteric dysplasia and to identify a genetic cause by whole-genome sequencing (WGS). The calf showed reduced fetal growth, a short-spine, a long and narrow face, cardiac defects and heterotopy of the spiral colon. Genetic analysis revealed a private heterozygous missense variant in MAP2K2:p.Arg179Trp, located in the protein kinase domain in the calf, and not found in more than 4500 control genomes including its sire. The identified variant affecting a conserved residue was predicted to be deleterious and most likely occurred de novo. This represents the first example of a dominant acting, and most likely pathogenic, variant in MAP2K2 in domestic animals, thereby providing the first MAP2K2-related large animal model, especially in respect to the enteric malformation. In addition, this study demonstrates the utility of WGS-based precise diagnostics for understanding sporadic congenital syndromic anomalies in cattle and the general utility of continuous surveillance for rare hereditary defects in cattle.Skeletal dysplasias encompass a clinical-, pathological- and genetically heterogeneous group of disorders characterized by abnormal cartilage and/or bone formation, growth, and remodeling. They may belong to the so-called RASopathies, congenital conditions caused by heterozygous variants in genes that encode components of the Ras/mitogen-activated protein kinase (MAPK) cell signaling pathway. Herein, an affected calf of the Italian Romagnola breed was reported showing a skeletal-cardio-enteric dysplasia. We identified a most likely disease-causing mutation in the MAP2K2 gene by whole-genome sequencing (WGS). The MAP2K2 gene is known to be related with dominant inherited cardio-facio-cutaneous syndrome in humans, but it was so far unknown to cause a similar disease in domestic animals. We assume that the identified missense variant that was predicted to impair the function of the protein, occurred either within the germline of the dam or post-zygotically in the embryo. Rare lethal diseases such as the skeletal-cardio-enteric dysplasia in livestock are usually not characterized to the molecular level, mainly because of the lack of funds and diagnostic opportunities. Precise WGS-based diagnostics enables the understanding of rare diseases and supports the value of monitoring cattle breeding populations for fatal genetic defects

Pressure induced softening of YB_6: pressure effect on the Ginzburg-Landau parameter \kappa=\lambda/\xi

Measurements of the transition temperature T_c, the second critical filed H_{c2} and the magnetic penetration depth \lambda under hydrostatic pressure (up to 9.2 kbar) in the YB_6 superconductor were carried out. A pronounced and {\it negative} pressure effects (PE) on T_c and H_{c2} with dT_c/dp=-0.0547(4) K/kbar and \mu_0dH_{c2}(0)/dp =-4.84(20) mT/kbar, and zero PE on \lambda(0) were observed. The PE on the coherence length d\xi(0)/dp=0.28(2) nm/kbar was calculated from the measured pressure dependence of H_{c2}(0). Together with the zero PE on the magnetic penetration depth \lambda(0), our results imply that the Ginzburg-Landau parameter \kappa(0)=\xi(0)/\lambda(0) depends on pressure and that pressure "softens" YB_6, e.g. moves it to the type-I direction.Comment: 4 pages, 2 figure

A De Novo Mutation in COL1A1 in a Holstein Calf with Osteogenesis Imperfecta Type II

Osteogenesis imperfecta (OI) type II is a genetic connective tissue disorder characterized by bone fragility, severe skeletal deformities and shortened limbs. OI usually causes perinatal death of affected individuals. OI type II diagnosis in humans is established by the identification of heterozygous mutations in genes coding for collagens. The purpose of this study was to characterize the pathological phenotype of an OI type II-affected neonatal Holstein calf and to identify the causative genetic variant by whole-genome sequencing (WGS). The calf had acute as well as intrauterine fractures, abnormally shaped long bones and localized arthrogryposis. Genetic analysis revealed a private heterozygous missense variant in COL1A1 (c.3917T>A) located in the fibrillar collagen NC1 domain (p.Val1306Glu) that most likely occurred de novo. This confirmed the diagnosis of OI type II and represents the first report of a pathogenic variant in the fibrillar collagen NC domain of COL1A1 associated to OI type II in domestic animals. Furthermore, this study highlights the utility of WGS-based precise diagnostics for understanding congenital disorders in cattle and the need for continued surveillance for rare lethal genetic disorders in cattle

MSSM Higgs Couplings to Bottom Quarks: Two-Loop Corrections

We present the two-loop SUSY-QCD corrections to the effective bottom Yukawa couplings within the minimal supersymmetric extension of the Standard Model. The effective Yukawa couplings include the resummation of the non-decoupling corrections Delta m_b for large values of tg(beta). We have derived the two-loop SUSY-QCD corrections to the leading SUSY-QCD and top-induced SUSY-electroweak contributions to Delta m_b. The scale dependence of the resummed Yukawa couplings is reduced from O(10%) to the per-cent level. These results reduce the theoretical uncertainties of the MSSM Higgs branching ratios to the accuracy which can be achieved at a future linear e+e- collider.Comment: 5 pages, 4 figure

Muon-Spin Rotation Study of the Ternary Noncentrosymmetric Superconductors Li2Pd x Pt3− x B

We investigated the superconducting state of the noncentrosymmetric superconductors Li2Pd x Pt3−x B with superconducting transition temperature T c=5.16(8)K (x=2.25), 3.56(8)K (x=1.5) and 2.60K (x=0) by means of muon-spin rotation (μSR) and specific heat experiments. The μSR relaxation rate σ sc was found to be constant at low temperatures for all the compounds. Data taken at different magnetic fields show that the magnetic penetration depth λ is field-independent for Li2Pd2.25Pt0.75B and Li2Pt3B. The electronic contribution to the specific heat measured in Li2Pd1.5Pt1.5B and Li2Pt3B increases exponentially at the lowest temperatures. These features suggest that the whole family of Li2Pd x Pt3−x B comprises single-gap s-wave superconductors across the entire doping regim

DYRK1B haploinsufficiency in a Holstein cattle with epilepsy.

In this study, epilepsy with focal seizures progressing to generalized seizures was diagnosed in a 6-month-old Holstein heifer. The seizures were characterized by a brief pre-ictal phase with depression and vocalization. During the ictal phase eyelid spasms, tongue contractions, nodding and abundant salivation were observed, rapidly followed by a convulsive phase with bilateral tonic, clonic or tonic-clonic activity and loss of consciousness. Finally, during the postictal phase the heifer was obtunded and disorientated, unable to perceive obstacles and hypermetric, and pressed its head against objects. In the inter-seizure phase, the heifer was clinically normal. Neuropathology revealed axonal degeneration in the brainstem and diffuse astrocytic hypertrophic gliosis. Whole genome sequencing of the affected heifer identified a private heterozygous splice-site variant in DYRK1B (NM_001081515.1: c.-101-1G>A), most likely resulting in haploinsufficiency owing to loss-of-function. This represents a report of a DYRK1B-associated disease in cattle and adds DYRK1B to the candidate genes for epilepsy

A de novo start-lost variant in ANKRD28 in a Holstein calf with dwarfism.

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Pixel-wise parameter adaptation for single-exposure extension of the image dynamic range

High dynamic range imaging is central in application fields like surveillance, intelligent transportation and advanced driving assistance systems. In some scenarios, methods for dynamic range extension based on multiple captures have shown limitations in apprehending the dynamics of the scene. Artifacts appear that can put at risk the correct segmentation of objects in the image. We have developed several techniques for the on-chip implementation of single-exposure extension of the dynamic range. We work on the upper extreme of the range, i. e. administering the available full-well capacity. Parameters are adapted pixel-wise in order to accommodate a high intra-scene range of illuminationsPeer reviewe