Thiamine and its mono-, di-, and triphosphoric esters content of normal rat tissues

Riassunto L'uso di un nuovo metodo cromatografico per la separazione della Tiamina e dei suoi esteri mono, di, e trifosforico nei tessuti animali ha permesso di definire, per la prima volta in termini quantitativi, la presenza del trifosfato nei tessuti stessi. L'organo più ricco di questo estere è il fegato, seguito dal cuore, dal rene e dal cervello nell'ordine.     

Phosphorylation of thiamine in the intestinal wall during absorption in vivo

Riassunto 2 h dopo l'introduzione di tiamina cloridrato o di tiaminpropildisolfuro nell'intestino tenue di ratto in vivo si trova un aumento significativo di tiamina fosforilata nella parete intestinale, essenzialmente a carico del tiamindifosfato.     

8-oxo-guanine bypass by human DNA polymerases in the presence of auxiliary proteins

Specialized DNA polymerases (DNA pols) are required for lesion bypass in human cells. Auxiliary factors have an important, but so far poorly understood, role. Here we analyse the effects of human proliferating cell nuclear antigen (PCNA) and replication protein A (RP-A) on six different human DNA pols--belonging to the B, Y and X classes--during in vitro bypass of different lesions. The mutagenic lesion 8-oxo-guanine (8-oxo-G) has high miscoding potential. A major and specific effect was found for 8-oxo-G bypass with DNA pols lambda and eta. PCNA and RP-A allowed correct incorporation of dCTP opposite a 8-oxo-G template 1,200-fold more efficiently than the incorrect dATP by DNA pol lambda, and 68-fold by DNA pol eta, respectively. Experiments with DNA-pol-lambda-null cell extracts suggested an important role for DNA pol lambda. On the other hand, DNA pol iota, together with DNA pols alpha, delta and beta, showed a much lower correct bypass efficiency. Our findings show the existence of an accurate mechanism to reduce the deleterious consequences of oxidative damage and, in addition, point to an important role for PCNA and RP-A in determining a functional hierarchy among different DNA pols in lesion bypass.     

Energy consumption,survey data and the prediction of industrial production in Italy: a comparison and combination of different models

We investigate the prediction of italian industrial production and first specify a model based on electricity consumption showing that the cubic trend in such a model mostly captures the evolution over time of the electricity coefficient, which can be well approximated by a smooth transition model, with no gains in predictive power. We also analyse the performance of models based on data of two different business surveys. According to the standard statistics of forecasting accuracy, the linear energy‐based model is not outperformed by any other model, nor by a combination of forecasts. However, a more comprehensive set of evaluation criteria sheds light on the relative merit of each individual model. A modelling strategy which makes full use of all information available is proposed. Copyright © 2000 John Wiley & Sons, Ltd.     

Regulatory T cells, mTOR kinase, and metabolic activity

The field that links immunity and metabolism is rapidly expanding. Apparently, non-immunological disorders such as obesity and type 2 diabetes have been linked to immune dysregulation, suggesting that metabolic alterations can be induced by or be a consequence of an altered self-immune tolerance. In this context, a key role is played by signaling systems acting as metabolic “sensors” linking energy/nutritional status to regulatory T (Treg) cell functions. We propose that a dynamic/oscillatory activity of intracellular metabolism, through mTOR modulation, might represent a shift in understanding the molecular mechanisms governing Treg cell tolerance. In particular, the decision between Treg cell proliferation and hyporesponsiveness arises from their ability to probe the extracellular milieu and, modulating the metabolic intracellular signaling, to determine different qualitative and quantitative functional outcomes.     

Gerodermia osteodysplastica is caused by mutations in SCYL1BP1, a Rab-6 interacting golgin

Gerodermia osteodysplastica is an autosomal recessive disorder characterized by wrinkly skin and osteoporosis. Here we demonstrate that gerodermia osteodysplastica is caused by loss-of-function mutations in SCYL1BP1, which is highly expressed in skin and osteoblasts. The protein localizes to the Golgi apparatus and interacts with Rab6, identifying SCYL1BP1 as a golgin. These results associate abnormalities of the secretory pathway with age-related changes in connective tissues.     

Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma

Hereditary pheochromocytoma (PCC) is often caused by germline mutations in one of nine susceptibility genes described to date, but there are familial cases without mutations in these known genes. We sequenced the exomes of three unrelated individuals with hereditary PCC (cases) and identified mutations in MAX, the MYC associated factor X gene. Absence of MAX protein in the tumors and loss of heterozygosity caused by uniparental disomy supported the involvement of MAX alterations in the disease. A follow-up study of a selected series of 59 cases with PCC identified five additional MAX mutations and suggested an association with malignant outcome and preferential paternal transmission of MAX mutations. The involvement of the MYC-MAX-MXD1 network in the development and progression of neural crest cell tumors is further supported by the lack of functional MAX in rat PCC (PC12) cells and by the amplification of MYCN in neuroblastoma and suggests that loss of MAX function is correlated with metastatic potential.