Identifying nonalcoholic fatty liver disease patients with active fibrosis by measuring extracellular matrix remodeling rates in tissue and blood.

Excess collagen synthesis (fibrogenesis) in the liver plays a causal role in the progression of nonalcoholic fatty liver disease (NAFLD). Methods are needed to identify patients with more rapidly progressing disease and to demonstrate early response to treatment. We describe here a novel method to quantify hepatic fibrogenesis flux rates both directly in liver tissue and noninvasively in blood. Twenty-one patients with suspected NAFLD ingested heavy water (2 H2 O, 50-mL aliquots) two to three times daily for 3-5 weeks prior to a clinically indicated liver biopsy. Liver collagen fractional synthesis rate (FSR) and plasma lumican FSR were measured based on 2 H labeling using tandem mass spectrometry. Patients were classified by histology for fibrosis stage (F0-F4) and as having nonalcoholic fatty liver or nonalcoholic steatohepatitis (NASH). Magnetic resonance elastography measurements of liver stiffness were also performed. Hepatic collagen FSR in NAFLD increased with advancing disease stage (e.g., higher in NASH than nonalcoholic fatty liver, positive correlation with fibrosis score and liver stiffness) and correlated with hemoglobin A1C. In addition, plasma lumican FSR demonstrated a significant correlation with hepatic collagen FSR.ConclusionUsing a well-characterized cohort of patients with biopsy-proven NAFLD, this study demonstrates that hepatic scar in NASH is actively remodeled even in advanced fibrosis, a disease that is generally regarded as static and slowly progressive. Moreover, hepatic collagen FSR correlates with established risks for fibrotic disease progression in NASH, and plasma lumican FSR correlates with hepatic collagen FSR, suggesting applications as direct or surrogate markers, respectively, of hepatic fibrogenesis in humans. (Hepatology 2017;65:78-88)

Two-loop representations of low-energy pion form factors and pi-pi scattering phases in the presence of isospin breaking

Dispersive representations of the pi-pi scattering amplitudes and pion form factors, valid at two-loop accuracy in the low-energy expansion, are constructed in the presence of isospin-breaking effects induced by the difference between the charged and neutral pion masses. Analytical expressions for the corresponding phases of the scalar and vector pion form factors are computed. It is shown that each of these phases consists of the sum of a "universal" part and a form-factor dependent contribution. The first one is entirely determined in terms of the pi-pi scattering amplitudes alone, and reduces to the phase satisfying Watson's theorem in the isospin limit. The second one can be sizeable, although it vanishes in the same limit. The dependence of these isospin corrections with respect to the parameters of the subthreshold expansion of the pi-pi amplitude is studied, and an equivalent representation in terms of the S-wave scattering lengths is also briefly presented and discussed. In addition, partially analytical expressions for the two-loop form factors and pi-pi scattering amplitudes in the presence of isospin breaking are provided.Comment: 57 pages, 12 figure

What is the (epsilon'/epsilon)_exp Telling Us ?

Nature might be kinder than previously thought as far as epsilon'/epsilon is concerned. We show that the recently obtained experimental value for epsilon'/epsilon does not require sizeable 1/N and isospin-breaking corrections. We propose to display the theoretical results for epsilon'/epsilon in a (P^{1/2}, P^{3/2}) plane in which the experimental result is represented by a (epsilon'/epsilon)_exp-path. This should allow to exhibit transparently the role of 1/N and isospin-breaking corrections in different calculations of epsilon'/epsilon. From now on theorists are allowed to walk only along this (epsilon'/epsilon)_exp-path.Comment: latex-file, 1 figure, 12 page

Assessment of Three Mitochondrial Genes (16S, Cytb, CO1) for Identifying Species in the Praomyini Tribe (Rodentia: Muridae)

The Praomyini tribe is one of the most diverse and abundant groups of Old World rodents. Several species are known to be involved in crop damage and in the epidemiology of several human and cattle diseases. Due to the existence of sibling species their identification is often problematic. Thus an easy, fast and accurate species identification tool is needed for non-systematicians to correctly identify Praomyini species. In this study we compare the usefulness of three genes (16S, Cytb, CO1) for identifying species of this tribe. A total of 426 specimens representing 40 species (sampled across their geographical range) were sequenced for the three genes. Nearly all of the species included in our study are monophyletic in the neighbour joining trees. The degree of intra-specific variability tends to be lower than the divergence between species, but no barcoding gap is detected. The success rate of the statistical methods of species identification is excellent (up to 99% or 100% for statistical supervised classification methods as the k-Nearest Neighbour or Random Forest). The 16S gene is 2.5 less variable than the Cytb and CO1 genes. As a result its discriminatory power is smaller. To sum up, our results suggest that using DNA markers for identifying species in the Praomyini tribe is a largely valid approach, and that the CO1 and Cytb genes are better DNA markers than the 16S gene. Our results confirm the usefulness of statistical methods such as the Random Forest and the 1-NN methods to assign a sequence to a species, even when the number of species is relatively large. Based on our NJ trees and the distribution of all intraspecific and interspecific pairwise nucleotide distances, we highlight the presence of several potentially new species within the Praomyini tribe that should be subject to corroboration assessments

Intrageneric relationships within Gerbilliscus (Rodentia, Muridae, Gerbillinae), with characterization of an additional West African species

International audienceThe systematics of the African rodent genus Gerbilliscus is still a matter of debate. At the genus level it has been said to include the related genus Gerbillurus, and at the species level some species still need to be definitely recognized as distinct. To tackle these questions, we gathered and analyzed mitochondrial (cytochrome b) and nuclear (BRCA1) gene sequences in a number of specimens representing ten species of Gerbilliscus and three species of Gerbillurus. Phylogenetic reconstructions confirm that Gerbillurus should be considered a synonym of Gerbilliscus. They also clearly show that species diversity in this group is spatially organized, with geographically well-defined species groups covering major areas of sub-Saharan Africa, namely Southern, Eastern and Western Africa. In the latter area, a well-supported genetic lineage appears to correspond to a hitherto overlooked species, also characterized by a distinctive karyotype. This species is characterized by an overall large size, a relatively long tail, a distinct karyotype, and represents a well-differentiated genetic cluster. It ranges from Benin to Guinea in Sudano-Guinean forest-savanna mosaic habitats, where it can be sympatric with the congeneric species G. kempi and G. guineae. Detailed body and skull morphological and biometrical analyses performed on samples of the West African species, including type specimens described in this region, suggest that this species may correspond to G. kempi. If confirmed, this would imply that what is currently named G. kempi would deserve another species name, the most likely of which would be G. giffardi

Intrageneric relationships and description of a new West African species in Gerbilliscus (Rodentia, Muridae, Gerbillinae)

International audienceThe systematics of the African rodent genus Gerbilliscus is still a matter of debate. At the genus level it has been said to include the related genus Gerbillurus, and at the species level some species still need to be definitely recognized as distinct. To tackle these questions, we gathered and analyzed mitochondrial (cytochrome b) and nuclear (BRCA1) gene sequences in a number of specimens representing ten species of Gerbilliscus and three species of Gerbillurus. Phylogenetic reconstructions confirm that Gerbillurus should be considered a synonym of Gerbilliscus. They also clearly show that species diversity in this group is spatially organized, with geographically well-defined species groups covering major areas of sub-Saharan Africa, namely Southern, Eastern and Western Africa. In the latter area, a well-supported genetic lineage appears to correspond to a hitherto overlooked species, also characterized by a distinctive karyotype. This species is characterized by an overall large size, a relatively long tail, a distinct karyotype, and represents a well-differentiated genetic cluster. It ranges from Benin to Guinea in Sudano-Guinean forest-savanna mosaic habitats, where it can be sympatric with the congeneric species G. kempi and G. guineae. Detailed body and skull morphological and biometrical analyses performed on samples of the West African species, including type specimens described in this region, suggest that this species may correspond to G. kempi. If confirmed, this would imply that what is currently named G. kempi would deserve another species name, the most likely of which would be G. giffardi

Intrageneric relationships within Gerbilliscus (Rodentia, Muridae, Gerbillinae), with characterization of an additional West African species

International audienceThe systematics of the African rodent genus Gerbilliscus is still a matter of debate. At the genus level it has been said to include the related genus Gerbillurus, and at the species level some species still need to be definitely recognized as distinct. To tackle these questions, we gathered and analyzed mitochondrial (cytochrome b) and nuclear (BRCA1) gene sequences in a number of specimens representing ten species of Gerbilliscus and three species of Gerbillurus. Phylogenetic reconstructions confirm that Gerbillurus should be considered a synonym of Gerbilliscus. They also clearly show that species diversity in this group is spatially organized, with geographically well-defined species groups covering major areas of sub-Saharan Africa, namely Southern, Eastern and Western Africa. In the latter area, a well-supported genetic lineage appears to correspond to a hitherto overlooked species, also characterized by a distinctive karyotype. This species is characterized by an overall large size, a relatively long tail, a distinct karyotype, and represents a well-differentiated genetic cluster. It ranges from Benin to Guinea in Sudano-Guinean forest-savanna mosaic habitats, where it can be sympatric with the congeneric species G. kempi and G. guineae. Detailed body and skull morphological and biometrical analyses performed on samples of the West African species, including type specimens described in this region, suggest that this species may correspond to G. kempi. If confirmed, this would imply that what is currently named G. kempi would deserve another species name, the most likely of which would be G. giffardi