Development of hepatocellular adenomas and carcinomas in mice with liver-specific G6Pase-α deficiency

Glycogen storage disease type 1a (GSD-1a) is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α), and is characterized by impaired glucose homeostasis and a high risk of developing hepatocellular adenomas (HCAs). A globally G6Pase-α-deficient (G6pc^−/−) mouse model that shows pathological features similar to those of humans with GSD-1a has been developed. These mice show a very severe phenotype of disturbed glucose homeostasis and rarely live beyond weaning. We generated liver-specific G6Pase-α-deficient (LS‑G6pc^−/−) mice as an alternative animal model for studying the long-term pathophysiology of the liver and the potential treatment strategies, such as cell therapy. LS‑G6pc^−/− mice were viable and exhibited normal glucose profiles in the fed state, but showed significantly lower blood glucose levels than their control littermates after 6 hours of fasting. LS‑G6pc^−/− mice developed hepatomegaly with glycogen accumulation and hepatic steatosis, and progressive hepatic degeneration. Ninety percent of the mice analyzed developed amyloidosis by 12 months of age. Finally, 25% of the mice sacrificed at age 10–20 months showed the presence of multiple HCAs and in one case late development of hepatocellular carcinoma (HCC). In conclusion, LS‑G6pc^−/− mice manifest hepatic symptoms similar to those of human GSD-1a and, therefore, represent a valid model to evaluate long-term liver pathogenesis of GSD-1a.KEY WORDS: Glycogen storage disease type 1a, Glucose-6-phosphatase-α, Animal model, Hepatomegaly, Hepatic steatosis, Hepatocellular adenoma, Hepatocellular carcinoma     

Identification and Molecular Characterization of ‘Candidatus Phytoplasma mali’ Isolates in North‐western Italy

Apple proliferation (AP) is an important disease and is prevalent in several European countries. The causal agent of AP is ‘Candidatus Phytoplasma mali’ (‘Ca. Phytoplasma mali’). In this work, isolates of ‘Ca. Phytoplasma mali’ were detected and characterized through polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses of 16S rRNA gene and non‐ribosomal DNA fragment. The presence of three AP subtypes (AT‐1, AT‐2 and AP‐15) was identified in 31 symptomatic apple trees and two samples each constituted by a pool of five insects, collected in north‐western Italy, where AT‐1 is a dominant subtype. Subsequent nucleotide sequence analysis of the PCR‐amplified 1.8 kb (P1/P7) fragment, containing the 16S rDNA, the 16S–23S intergenic ribosomal region and the 5′‐end of the 23S rDNA, revealed the presence of at least two phytoplasmal genetic lineages within the AT‐1 subtype, designed AT‐1a and AT‐1b. Moreover, in silico single nucleotide polymorphism (SNP) analysis based on 16S rDNA sequence can differentiate AT‐1 subtype from AT‐2 and AP‐15 subtypes. Our data showed a high degree of genetic diversity among ‘Ca. Phytoplasma mali’ population in north‐western Italy and underlined the possible use of the 16S rDNA analysis for the identification and the geographical origin assignation of isolates of AP phytoplasma. Molecular markers on 16S rDNA, here identified, could be useful for studying the epidemiology of AP disease.     

The epithelial bell

The epithelial bell which surrounds the clitoris in most mammals arises by fusion of visceral and parietal layers of the prepuce. Adhesion of the epithelia occurs between the squamous cells and a normal connection is formed by desmosomes and other junctions. There is total absence of cornifications. The squamous epithelial double lamina splits occasionally in some patches where the free surfaces are getting back to a normal process of keratinization as in the wall of the vestibule. In the closed pits the keratin scales form squamous granules without sebaceous secretion. Sometimes a similar process occurs in the human prepuce with the same results as described in cat and rabbit. The granules of keratin are different from the smegmaliths as they do not contain sebaceous secretion.     

Anthropometric variables,lifestyle and sports in school-age children: Comparison between the cities of Bologna and Crotone

Weight disorders are rapidly increasing in childhood. In Italy a strong geographic North-South gradient of overweight and obesity has been reported. The purpose of this study is to examine anthropometric variables, physical activity and lifestyles in school-age children in the cities of Bologna and Crotone.     

An atrial hematopoietic locus in the heart of the cave salamander (urodele amphibian)

Lungless Salamanders of the family Plethodontidae have a reduced interatrial septum. The pulmonary vein is lacking. In these species, the septum as a membranous thin sheet attaches near the dorsal lip of the sino-atrial valve where a connective and muscular column, supporting the valve, extends its branches over the upper wall of the undivided atrial cavity where a sponge-like structure is formed. The meshes of this structure are the site of a erythropoietic activity as shown in the plates. Early stages in active reproduction are found in the external acid layer while in the basic inner layer the red cells undergo differentiation. This locus may be correlated to the particular anatomy of the heart concerning the lacking of the pulmonary vein, the position of the sino-arterial aperture shifted to the left side and the reduced interatrial septum. In the large upper cavity of the atrium a certain degree of blood stagnation could be possible which could allow the settlement of this locus. No ventricular erythropoiesis nor epicardial granulopoiesis have been found. This hemopoietic locus is lacking in the family Salamandridae and Anura.     

A rat mammary gland cancer cell with stem cell properties of self-renewal and multi-lineage differentiation

The cancer stem cell hypothesis posits that tumors are derived from a single cancer-initiating cell with stem cell properties. The task of identifying and characterizing cancer-initiating cells with stem cell properties at the single cell level has proven technically difficult because of the scarcity of the cancer stem cells in the tissue of origin and the lack of specific markers for cancer stem cells. Here we show that a single LA7 cell, derived from rat mammary adenocarcinoma has: the ability to serially re-generate mammospheres in long-term non-adherent cultures, the differentiation potential to generate all the cell lineages of the mammary gland and branched duct-like structures that recapitulate morphologically and functionally the ductal–alveolar-like architecture of the mammary tree. The properties of self-renewal, extensive capacity for proliferation, multi-lineage differentiation and the tubular-like structure formation potential suggest that LA7 cells is a cancer stem model system to study the dynamics of tumor formation at the single cell level. Cinzia Cocola, Sveva Sanzone and Simonetta Astigiano have contributed equally to this work.