Novel therapeutic approaches based on the pathological role of gut dysbiosis on the link between nonalcoholic fatty liver disease and insulin resistance.

The growing global epidemic of obesity and type 2 diabetes mellitus has determined an increased prevalence of NAFLD (non-alcoholic fatty liver disease), making it the most common chronic liver disease in the Western world and a leading cause of liver transplantation. In the last few years, a rising number of studies conducted both on animal and human models have shown the existence of a close association between insulin resistance (IR), dysbiosis, and steatosis. However, all the mechanisms that lead to impaired permeability, inflammation, and fibrosis have not been fully clarified. Recently, new possible treatment modalities have received much attention. To reach the review purpose, a broad-ranging literature search on multidisciplinary research databases was performed using the following terms alone or in combination: "NAFLD", "gut dysbiosis", "insulin resistance", "inflammation", "probiotics", "Chinese herbs". The use of probiotics, prebiotics, symbiotics, postbiotics, fecal microbiota transplant (FMT), Chinese herbal medicine, antibiotics, diet (polyphenols and fasting diets), and minor therapies such as carbon nanoparticles, the MCJ protein, water rich in molecular hydrogen, seems to be able to improve the phenotypic pattern in NAFLD patients. In this review, we provide an overview of how IR and dysbiosis contribute to the development and progression of NAFLD, as well as the therapeutic strategies currently in use.

Chloroplast Microsatellite Diversity in Phaseolus vulgaris.

Evolutionary studies that are aimed at defining the processes behind the present level and organization of crop genetic diversity represent the fundamental bases for biodiversity conservation and use. A Mesoamerican origin of the common bean Phaseolus vulgaris was recently suggested through analysis of nucleotide polymorphism at the nuclear level. Here, we have used chloroplast microsatellites to investigate the origin of the common bean, on the basis of the specific characteristics of these markers (no recombination, haploid genome, uniparental inheritance), to validate these recent findings. Indeed, comparisons of the results obtained through analysis of nuclear and cytoplasmic DNA should allow the resolution of some of the contrasting information available on the evolutionary processes. The main outcomes of the present study are: (i) confirmation at the chloroplast level of the results obtained through nuclear data, further supporting the Mesoamerican origin of P. vulgaris, with central Mexico representing the cradle of its diversity; (ii) identification of a putative ancestral plastidial genome, which is characteristic of a group of accessions distributed from central Mexico to Peru, but which have not been highlighted beforehand through analyses at the nuclear level. Finally, the present study suggests that when a single species is analyzed, there is the need to take into account the complexity of the relationships between P. vulgaris and its closely related and partially intercrossable species P. coccineus and P. dumosus. Thus, the present study stresses the importance for the investigation of the speciation processes of these taxa through comparisons of both plastidial and nuclear variability. This knowledge will be fundamental not only from an evolutionary point of view, but also to put P. coccineus and P. dumosus germplasm to better use as a source of useful diversity for P. vulgaris breeding.

Nucleotide diversity of a genomic sequence similar to SHATTERPROOF (PvSHP1) in domesticated and wild common bean (Phaseolus vulgaris L.).

Evolutionary studies in plant and animal breeding are aimed at understanding the structure and organization of genetic variations of species. We have identified and characterized a genomic sequence in Phaseolus vulgaris of 1,200 bp (PvSHP1) that is homologous to SHATTERPROOF-1 (SHP1), a gene involved in control of fruit shattering in Arabidopsis thaliana. The PvSHP1 fragment was mapped to chromosome Pv06 in P. vulgaris and is linked to the flower and seed color gene V. Amplification of the PvSHP1 sequence from the most agronomically important legume species showed a high degree of interspecies diversity in the introns within the Phaseoleae, while the coding region was conserved across distant taxa. Sequencing of the PvSHP1 sequence in a sample of 91 wild and domesticated genotypes that span the geographic distribution of this species in the centers of origin showed that PvSHP1 is highly polymorphic and, therefore, particularly useful to further investigate the origin and domestication history of P. vulgaris. Our data confirm the gene pool structure seen in P. vulgaris along with independent domestication processes in the Andes and Mesoamerica; they provide additional evidence for a single domestication event in Mesoamerica. Moreover, our results support the Mesoamerican origin of this species. Finally, we have developed three indel-spanning markers that will be very useful for bean germplasm characterization, and particularly to trace the distribution of the domesticated Andean and Mesoamerican gene pools.

Genetic diversity and geographic differentiation in the alternative legume Tripodion tetraphyllum (L.) Fourr. in North African populations.

Wild legumes constitute an important component of widespread pastures in the Mediterranean basin. This region is experiencing remarkable effects from climate change, and continuous monitoring of species and population dynamics is important in order to plan and enact valuable conservation programmes. Tripodion tetraphyllum (L.) Fourr. [=Anthyllis tetraphylla L.] (2n=16), belongs to the tribe Loteae (Fabaceae), and could be very important for soil protection and sward improvement in abandoned or degraded Mediterranean areas. This alternative pasture legume is very closely related to Lotus japonicus and has some important characteristics for survival of the species in difficult and overgrazed Mediterranean areas. In this study, we have investigated the molecular diversity and population structure of T. tetraphyllum from North Africa using ISSR markers and plastidial microsatellites. To date, this is the first study concerning the genetic diversity and geographic differentiation of T. tetraphyllum. Ninety genotypes from three North African countries were analysed according to ISSRs, cpSSRs and one phenotypic trait. T. tetraphyllum shows a clear geographical structure, with differentiation associated with longitudinal differences; moreover, there is a general reduction in genetic diversity from Morocco to Tunisia. With all the markers used, strong differentiation was seen among collection sites. Our data highlight a genetic diversity gradient and cline of distribution, indicating that T. tetraphyllum has extended its area of distribution from Morocco to Tunisia.

Genetic diversity and structure of a worldwide collection of Phaseolus coccineus L.

Phaseolus coccineus L. is closely related to P. vulgaris and is the third most important cultivated Phaseolus species. Little is known about the patterns of its diversity. In this work, a representative collection of its worldwide diversity was initially developed. The collection includes 28 wild forms (WFs) and 52 landraces (LRs) from Mesoamerica (the crop domestication area), and 148 LRs from Europe (where the crop was introduced in the sixteenth century). The collection was studied by using 12 SSR molecular markers that were developed for the P. vulgaris genome. They were proved to be effective and reliable in P. coccineus in this work. Fourteen LRs of P. dumosus (previously identified as a subspecies of P. coccineus) were also studied. The genetic diversity, population structure and phylogenetic relationships were investigated. The results indicate that: (a) the European and Mesoamerican gene pools are clearly differentiated, (b) a certain reduction of diversity occurred with introduction into Europe, and (c) the Mesoamerican LRs (P. dumosus included) and WFs are closely related and are connected by a high gene flow. Inferences on the domestication process of P. coccineus are also presented. This study provides a picture of the genetic diversity distribution and outcomes with introduction into the Old World, which was not available before. It also underlines that the genetic diversity of both WFs and LRs is an important source for Phaseolus spp. breeding programs and deserves to be preserved in situ and ex situ.

Beans in Europe: origin and structure of the European landraces of Phaseolus vulgaris L.

This study focuses on the expansion of Phaseolus vulgaris in Europe. The pathways of distribution of beans into and across Europe were very complex, with several introductions from the New World that were combined with direct exchanges between European and other Mediterranean countries. We have analyzed here six chloroplast microsatellite (cpSSR) loci and two unlinked nuclear loci (for phaseolin types and Pv-shatterproof1). We have assessed the genetic structure and level of diversity of a large collection of European landraces of P. vulgaris (307) in comparison to 94 genotypes from the Americas that are representative of the Andean and Mesoamerican gene pools. First, we show that most of the European common bean landraces (67%) are of Andean origin, and that there are no strong differences across European regions for the proportions of the Andean and Mesoamerican gene pools. Moreover, cytoplasmic diversity is evenly distributed across European regions. Secondly, the cytoplasmic bottleneck that was due to the introduction of P. vulgaris into the Old World was very weak or nearly absent. This is in contrast to evidence from nuclear analyses that have suggested a bottleneck of greater intensity. Finally, we estimate that a relatively high proportion of the European bean germplasm (about 44%) was derived from hybridization between the Andean and Mesoamerican gene pools. Moreover, although hybrids are present everywhere in Europe, they show an uneven distribution, with high frequencies in central Europe, and low frequencies in Spain and Italy. On the basis of these data, we suggest that the entire European continent and not only some of the countries therein can be regarded as a secondary diversification center for P. vulgaris. Finally, we outline the relevance of these inter-gene pool hybrids for plant breeding.

Introgression from modern hybrid varieties into landrace populations of maize (Zea mays ssp. mays L.) in central Italy.

Landraces are domesticated local plant varieties that did not experience a deliberate and intensive selection during a formal breeding programme. In Europe, maize landraces are still cultivated, particularly in marginal areas where traditional farming is often practiced. Here, we have studied the evolution of flint maize landraces from central Italy over 50 years of on-farm cultivation, when dent hybrid varieties were introduced and their use was widespread. We have compared an 'old' collection, obtained during the 1950s, before the introduction of hybrids, and a recent collection of maize landraces. For comparison, a sample of maize landraces from north Italy, and of improved germplasm, including hybrids and inbred lines were also used. A total of 296 genotypes were analysed using 21 microsatellites. Our results show that the maize landraces collected in the last 5-10 years have evolved directly from the flint landrace gene pool cultivated in central Italy before the introduction of modern hybrids. The population structure, diversity and linkage disequilibrium analyses indicate a significant amount of introgression from hybrid varieties into the recent landrace populations. No evidence of genetic erosion of the maize landraces was seen, suggesting that in situ conservation of landraces is an efficient strategy for preserving genetic diversity. Finally, the level of introgression detected was very variable among recent landraces, with most of them showing a low level of introgression; this suggests that coexistence between different types of agriculture is possible, with the adoption of correct practices that are aimed at avoiding introgression from undesired genetic sources.

Prenatal diagnosis of focal nodular hyperplasia of the liver.

A case of focal nodular hyperplasia of the liver presenting in a 36-week-old fetus is reported. The tumour appeared on antenatal ultrasound as a 4.0 cm x 3.0 cm x 2.7 cm hypoechoic mass at the periphery of the right lobe of the liver. Colour Doppler imaging showed it to have prominent vascularity. Postnatally, sonography confirmed the presence of a vascular mass within the liver. The tumour was removed at laparotomy and was diagnosed as an area of focal nodular hyperplasia on histopathological examination.

Blood lead levels in children living in three communities, at different risks of lead pollution.

We carried out a survey on blood lead levels in children living in three different communities in Umbria, Italy: Corciano, a small community (12,500 inhabitants), free of lead-using factories and with light traffic; Perugia, a medium-sized city (146,500 inhabitants); Deruta, a small community (7500 inhabitants) whose economy is based mainly on the production of artistic pottery, mostly in small home-operated factories. The study sample was made up of 539 children (275 boys and 264 girls); 156 of them attended nursery school (aged 3-6) and 383 primary school (aged 6-11). The mean blood lead level was significantly higher in Deruta than in Corciano (9.7 vs 8.3 micrograms/dl); Deruta children whose parents were occupationally exposed to lead had significantly higher blood lead levels than children of lead-unexposed parents (10.7 vs 9.0 micrograms/dl). The mean blood lead level was higher in Perugia than in Corciano children. On the average boys had higher blood lead levels than girls in all of the groups. We conclude that blood lead levels were low in the groups of children studied. Nevertheless children of ceramic workers and children living in a medium-sized city had greater lead absorption than children living in the control area.