Biomedical subjects

Fabio Luciani

Publications and source records attributed to Fabio Luciani.

4 recordsLinked to original sources

PubMed2006

Using approximate Bayesian computation to estimate tuberculosis transmission parameters from genotype data.

Tuberculosis can be studied at the population level by genotyping strains of Mycobacterium tuberculosis isolated from patients. We use an approximate Bayesian computational method in combination with a stochastic model of tuberculosis transmission and mutation of a molecular marker to estimate the net transmission rate, the doubling time, and the reproductive value of the pathogen. This method is applied to a published data set from San Francisco of tuberculosis genotypes based on the marker IS6110. The mutation rate of this marker has previously been studied, and we use those estimates to form a prior distribution of mutation rates in the inference procedure. The posterior point estimates of the key parameters of interest for these data are as follows: net transmission rate, 0.69/year [95% credibility interval (C.I.) 0.38, 1.08]; doubling time, 1.08 years (95% C.I. 0.64, 1.82); and reproductive value 3.4 (95% C.I. 1.4, 79.7). These figures suggest a rapidly spreading epidemic, consistent with observations of the resurgence of tuberculosis in the United States in the 1980s and 1990s.

Algorithms↗

PubMed2005

A mathematical model of protein degradation by the proteasome.

The proteasome is the major protease for intracellular protein degradation. The influx rate of protein substrates and the exit rate of the fragments/products are regulated by the size of the axial channels. Opening the channels is known to increase the overall degradation rate and to change the length distribution of fragments. We develop a mathematical model with a flux that depends on the gate size and a phenomenological cleavage mechanism. The model has Michaelis-Menten kinetics with a V(max) that is inversely related to the length of the substrate, as observed in the in vitro experiments. We study the distribution of fragment lengths assuming that proteasomal cleavage takes place at a preferred distance from the ends of a protein fragment, and find multipeaked fragment length distributions similar to those found experimentally. Opening the gates in the model increases the degradation rate, increases the average length of the fragments, and increases the peak in the distribution around a length of 8-10 amino acids. This behavior is also observed in immunoproteasomes equipped with PA28. Finally, we study the effect of re-entry of processed fragments in the degradation kinetics and conclude that re-entry is only expected to affect the cleavage dynamics when short fragments enter the proteasome much faster than the original substrate. In summary, the model proposed in this study captures the known characteristics of proteasomal degradation, and can therefore help to quantify MHC class I antigen processing and presentation.

Antigen Presentation↗

PubMed2003

Leptin fails to reduce ethanol intake in Marchigian Sardinian alcohol-preferring rats.

Leptin, a hormone secreted by the adipocytes and involved in feeding and energy balance control, has been proposed to modulate alcohol craving in mice and humans. This study evaluated whether leptin modulates alcohol intake in Marchigian Sardinian alcohol-preferring (msP) rats. Rats were offered 10% ethanol either 2h per day at the beginning of dark period of the 12:12h light/dark cycle, or 24h per day. Leptin was injected into the lateral ventricle (LV), the third ventricle (3V), or intraperitoneally (IP) once a day, 1h before the onset of the dark period. Neither acute nor chronic (9 days) leptin injections (1 or 8microg per rat) into the LV or 3V modified ethanol intake in male msP rats, offered ethanol 2h per day. Chronic LV injection of leptin (8 or 32 microg per rat in male rats and 8 or 16 microg per rat in female rats for 7 days), or chronic IP injections of leptin (1mg/kg in male rats for 5 days) failed to modify the intake of ethanol, offered 24h per day. Finally, chronic LV leptin injections (8 or 32 microg per rat for 12 days) did not modify ethanol intake in male msP rats, adapted to ad libitum access to ethanol and then tested after a 6-day period of ethanol deprivation. In contrast, in most of these conditions leptin significantly reduced food intake. These data do not support a role for leptin in alcohol intake, preference, or craving in msP rats.

Alcohol Drinking↗

PubMed2003

Lymphocyte DNA alteration by sub-chronic ethanol intake in alcohol-preferring rats.

BACKGROUND: Excessive alcohol consumption has been correlated with a higher susceptibility to infections among humans. Chromosome aberrations and other parameters have been suggested as useful biomarkers in assessing genetic damage due to ethanol intake. METHODS: Genetically selected alcohol-preferring rats were given water, 10% ethanol and water or 10% ethanol alone for 3 months as fluid to drink. Food was available ad libitum for the entire period. At the end of the sub-chronic treatment their blood and liver were collected. All blood cells were counted and both lymphocytes and hepatocytes of all three groups were tested with the Comet assay to determine whether any DNA damage had occurred. RESULTS: Only lymphocytes showed DNA damage, with differences among groups. The group that had only ethanol to drink showed greater lymphocyte DNA damage than the ethanol/water and water alone groups. On the other hand, hepatocyte DNA did not show any signs of damage. CONCLUSIONS: Ten weeks of sub-chronic ethanol treatment produces small but significant damage to lymphocytes but not to hepatocytes, a result which confirms the observations of previous authors, and extends them even to a strain of rats genetically selected for high ethanol intake.

Alcohol Drinking↗