Improvement of clinical and laboratory parameters in a canine with idiopathic chronic hepatitis after transplantation of allogeneic mesenchymal cells derived from bone marrow - case report

ABSTRACT Chronic hepatitis (CH) is characterized by the replacement of hepatocytes for fibrotic tissue after injury, and treatment is not curative. Stem cell therapy has shown potential to reduce liver fibrosis. This report describes the management of a dog with CH with a mesenchymal cell-based approach. A 13-year old dog was presented with weight loss, vomiting, diarrhea, and lethargy. She was previously diagnosed with CH. Blood analysis showed hypoalbuminemia, increased serum activities of alanine aminotransferase (ALT) and alkaline phosphatase (ALP), and anemia. Three 2.5x106 bone marrow-derived mesenchymal cells transplantations were performed. After the first transplantation, the owner reported an improvement in clinical signs. Biochemistry evidenced a reduction in ALP activity. After the second administration, serum biochemistry showed a decrease in serum ALT and ALP activities, which kept falling after the third transplantation. There was an increase in albumin and total plasmatic proteins concentration. After six months, the dog came back for control and further improvement in clinical signs, new decrease in ALT activity and a mild increase in ALP concentration was observed. Increase in total and plasmatic protein were also observed. Stem cell-based therapy may be considered a promising alternative for liver diseases. It was safe and showed efficacy in this report

Electromagnetic transitions in an effective chiral Lagrangian with the eta-prime and light vector mesons

We consider the chiral Lagrangian with a nonet of Goldstone bosons and a nonet of light vector mesons. The mixing between the pseudoscalar mesons eta and eta-prime is taken into account. A novel counting scheme is suggested that is based on hadrogenesis, which conjectures a mass gap in the meson spectrum of QCD in the limit of a large number of colors. Such a mass gap would justify to consider the vector mesons and the eta-prime meson as light degrees of freedom. The complete leading order Lagrangian is constructed and discussed. As a first application it is tested against electromagnetic transitions of light vector mesons to pseudoscalar mesons. Our parameters are determined by the experimental data on photon decays of the omega, phi and eta-prime meson. In terms of such parameters we predict the corresponding decays into virtual photons with either dielectrons or dimuons in the final state.Comment: 17 pages, extended discussion on mixin

Chiral effective field theories of the strong interactions

Effective field theories of the strong interactions based on the approximate chiral symmetry of QCD provide a model-independent approach to low-energy hadron physics. We give a brief introduction to mesonic and baryonic chiral perturbation theory and discuss a number of applications. We also consider the effective field theory including vector and axial-vector mesons.Comment: 22 pages, 9 figures, proceedings of "Many-Body Structure of Strongly Interacting Systems", Mainz, Germany, Feb. 23-25 201

Gene family information facilitates variant interpretation and identification of disease-associated genes in neurodevelopmental disorders

Abstract Background Classifying pathogenicity of missense variants represents a major challenge in clinical practice during the diagnoses of rare and genetic heterogeneous neurodevelopmental disorders (NDDs). While orthologous gene conservation is commonly employed in variant annotation, approximately 80% of known disease-associated genes belong to gene families. The use of gene family information for disease gene discovery and variant interpretation has not yet been investigated on a genome-wide scale. We empirically evaluate whether paralog-conserved or non-conserved sites in human gene families are important in NDDs. Methods Gene family information was collected from Ensembl. Paralog-conserved sites were defined based on paralog sequence alignments; 10,068 NDD patients and 2078 controls were statistically evaluated for de novo variant burden in gene families. Results We demonstrate that disease-associated missense variants are enriched at paralog-conserved sites across all disease groups and inheritance models tested. We developed a gene family de novo enrichment framework that identified 43 exome-wide enriched gene families including 98 de novo variant carrying genes in NDD patients of which 28 represent novel candidate genes for NDD which are brain expressed and under evolutionary constraint. Conclusion This study represents the first method to incorporate gene family information into a statistical framework to interpret variant data for NDDs and to discover new NDD-associated genes

Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients

Objective To characterize, among European and Han Chinese populations, the genetic predictors of maculopapular exanthema (MPE), a cutaneous adverse drug reaction common to antiepileptic drugs. Methods We conducted a case-control genome-wide association study of autosomal genotypes, including Class I and II human leukocyte antigen (HLA) alleles, in 323 cases and 1,321 drug-tolerant controls from epilepsy cohorts of northern European and Han Chinese descent. Results from each cohort were meta-analyzed. Results We report an association between a rare variant in the complement factor H–related 4 (CFHR4) gene and phenytoin-induced MPE in Europeans (p = 4.5 × 10–11; odds ratio [95% confidence interval] 7 [3.2–16]). This variant is in complete linkage disequilibrium with a missense variant (N1050Y) in the complement factor H (CFH) gene. In addition, our results reinforce the association between HLA-A*31:01 and carbamazepine hypersensitivity. We did not identify significant genetic associations with MPE among Han Chinese patients. Conclusions The identification of genetic predictors of MPE in CFHR4 and CFH, members of the complement factor H–related protein family, suggest a new link between regulation of the complement system alternative pathway and phenytoin-induced hypersensitivity in European-ancestral patients

The Physics of Star Cluster Formation and Evolution

© 2020 Springer-Verlag. The final publication is available at Springer via https://doi.org/10.1007/s11214-020-00689-4.Star clusters form in dense, hierarchically collapsing gas clouds. Bulk kinetic energy is transformed to turbulence with stars forming from cores fed by filaments. In the most compact regions, stellar feedback is least effective in removing the gas and stars may form very efficiently. These are also the regions where, in high-mass clusters, ejecta from some kind of high-mass stars are effectively captured during the formation phase of some of the low mass stars and effectively channeled into the latter to form multiple populations. Star formation epochs in star clusters are generally set by gas flows that determine the abundance of gas in the cluster. We argue that there is likely only one star formation epoch after which clusters remain essentially clear of gas by cluster winds. Collisional dynamics is important in this phase leading to core collapse, expansion and eventual dispersion of every cluster. We review recent developments in the field with a focus on theoretical work.Peer reviewe

The design, construction, and commissioning of the KATRIN experiment

The KArlsruhe TRItium Neutrino (KATRIN) experiment, which aims to make a direct and model-independent determination of the absolute neutrino mass scale, is a complex experiment with many components. More than 15 years ago, we published a technical design report (TDR) [1] to describe the hardware design and requirements to achieve our sensitivity goal of 0.2 eV at 90% C.L. on the neutrino mass. Since then there has been considerable progress, culminating in the publication of first neutrino mass results with the entire beamline operating [2]. In this paper, we document the current state of all completed beamline components (as of the first neutrino mass measurement campaign), demonstrate our ability to reliably and stably control them over long times, and present details on their respective commissioning campaigns