Search PubMed⌕ Search

Biomedical subjects

F Taddei

Publications and source records attributed to F Taddei.

At least 37 records · Page 2Linked to original sources

Counteraction by MutT protein of transcriptional errors caused by oxidative damage.

Oxidized guanine (8-oxo-7,8-dihydroguanine; 8-oxo-G) is a potent mutagen because of its ambiguous pairing with cytosine and adenine. The Escherichia coli MutT protein specifically hydrolyzes both 8-oxo-deoxyguanosine triphosphate (8-oxo-dGTP) and 8-oxo-guanosine triphosphate (8-oxo-rGTP), which are otherwise incorporated in DNA and RNA opposite template A. In vivo, this cleaning of the nucleotide pools decreases both DNA replication and transcription errors. The effect of mutT mutation on transcription fidelity was shown to depend on oxidative metabolism. Such control of transcriptional fidelity by the ubiquitous MutT function has implications for evolution of RNA-based life, phenotypic expression, adaptive mutagenesis, and functional maintenance of nondividing cells.

Aerobiosis↗

Molecular keys to speciation: DNA polymorphism and the control of genetic exchange in enterobacteria.

Speciation involves the establishment of genetic barriers between closely related organisms. The extent of genetic recombination is a key determinant and a measure of genetic isolation. The results reported here reveal that genetic barriers can be established, eliminated, or modified by manipulating two systems which control genetic recombination, SOS and mismatch repair. The extent of genetic isolation between enterobacteria is a simple mathematical function of DNA sequence divergence. The function does not depend on hybrid DNA stability, but rather on the number of blocks of sequences identical in the two mating partners and sufficiently large to allow the initiation of recombination. Further, there is no obvious discontinuity in the function that could be used to define a level of divergence for distinguishing species.

Biological Evolution↗

Role of mutator alleles in adaptive evolution.

Because most newly arising mutations are neutral or deleterious, it has been argued that the mutation rate has evolved to be as low as possible, limited only by the cost of error-avoidance and error-correction mechanisms. But up to one per cent of natural bacterial isolates are 'mutator' clones that have high mutation rates. We consider here whether high mutation rates might play an important role in adaptive evolution. Models of large, asexual, clonal populations adapting to a new environment show that strong mutator genes (such as those that increase mutation rates by 1,000-fold) can accelerate adaptation, even if the mutator gene remains at a very low frequency (for example, 10[-5]). Less potent mutators (10 to 100-fold increase) can become fixed in a fraction of finite populations. The parameters of the model have been set to values typical for Escherichia coli cultures, which behave in a manner similar to the model in long-term adaptation experiments.

Adaptation, Physiological↗

Genetic variability and adaptation to stress.

Besides an immediate cellular adaptation to stress, organisms can resist such challenges through changes in their genetic material. These changes can be due to mutation or acquisition of pre-evolved functions via horizontal transfer. In this chapter we will review evidence from bacterial genetics that suggests that the frequency of such events can increase in response to stress by activating mutagenic response (e.g. the SOS response) and by inhibiting antimutagenic activities (e.g. mismatch repair system, MRS). Natural selection, by favoring adaptations, can also select for the mechanism(s) that has/have generated the adaptive changes by hitchhiking. These mutator mechanisms can sometimes respond very specifically, though blindly, to the challenge of the environment. Such stress-induced increases in mutation rates enhance genetic polymorphism, which is the structural component of the barrier to genetic exchange. Since SOS and MRS are the enzymatic controls of this barrier, the modulation of these systems can lead to a burst of speciation.

Adaptation, Physiological↗

Genetic analysis of mutagenesis in aging Escherichia coli colonies.

Bacteria live in unstructured and structured environments, experiencing feast and famine lifestyles. Bacterial colonies can be viewed as model structured environments. SOS induction and mutagenesis have been observed in aging Escherichia coli colonies, in the absence of exogenous sources of DNA damage. This cAMP-dependent mutagenesis occurring in Resting Organisms in a Structured Environment (ROSE) is unaffected by a umuC mutation and therefore differs from both targeted UV mutagenesis and recA730 (SOS constitutive) untargeted mutagenesis. As a recB mutation has only a minor effect on ROSE mutagenesis it also differs from both adaptive reversion of the lacI33 allele and from iSDR (inducible Stable DNA Replication) mutagenesis. Besides its recA and lexA dependence, ROSE mutagenesis is also uvrB and polA dependent. These genetic requirements are reminiscent of the untargeted mutagenesis in lambda phage observed when unirradiated lambda infects UV-irradiated E. coli. These mutations, which are not observed in aging liquid cultures, accumulate linearly with the age of the colonies. ROSE mutagenesis might offer a good model for bacterial mutagenesis in structured environments such as biofilms and for mutagenesis of quiescent eukaryotic cells.

Bacterial Proteins↗

[Doppler examination of the fetal left and right pulmonary artery. Relation to fetal position and gestational age: a methodological study].

UNLABELLED: A Methodical Study: AIM OF THE STUDY: To analyse the feasibility of colour and spectral Doppler assessment of blood flow in the fetal right (RPA) and left (LPA) main pulmonary arteries in relation to fetal position and to gestational age. STUDY DESIGN: The fetal position was a priori divided into 3 types, depending on whether the fetal heart was visualised apically (Type 1), from the right side (Type 2) or from the left side (Type 3). Three groups A (19-25 weeks gestation), B (26-32) and C (33-39) including 33 consecutive pregnancies each, were examined to document the fetal position as well as the rate of the successful Doppler examinations of the RPA and/or LPA. RESULTS: The fetal position Type 2 was most common throughout gestation (in group A = 42%, B = 36%, C = 51%) followed by the type 3 and then type 1. The rate of successful Doppler records from the RPA and LPA depended on the fetal position: In Type 2 RPA in 98%; in Type 3, LPA in 100%; but the apical approach was not effective (< 40%). Depending on gestational age, the success rates for a Doppler examination of at least one vessel were high (> 85%), whereas successful examination of both vessels was unlikely (12%). CONCLUSIONS: In the second half of pregnancy, independent of fetal position, Doppler examination of at least one pulmonary artery is successful in most cases, whereas the assessment of both vessels is rather difficult.

Female↗

Genetic barriers among bacteria.

Barriers to chromosomal gene transfer between bacterial species control their genetic isolation. These barriers, such as different microhabitats, the host ranges of genetic exchange vectors and restriction-modification systems, limit gene exchange, but the major limitation is genomic sequence divergence. The mismatch-repair system inhibits interspecies recombination, the inducible SOS system stimulates interspecies recombination, while natural selection determines the effective recombination frequencies.

Bacteria↗

Blood flow velocity waveforms from peripheral pulmonary arteries in normally grown and growth-retarded fetuses.

The objective of this study was to describe blood flow velocity waveforms of fetal peripheral pulmonary arteries in normally grown and growth-retarded fetuses. Doppler studies were performed in 182 normally grown fetuses (gestational age 18-40 weeks) and in 61 growth-retarded fetuses (gestational age 24-36 weeks) that were free from structural and chromosomal abnormalities and whose umbilical and middle cerebral artery Doppler findings suggested uteroplacental insufficiency as the most likely etiology of the growth defect. The pulsatility index was used to quantify the velocity waveforms. Successful recordings were obtained in 90.1% of the normally grown and 93.4% of the growth-retarded fetuses. In normally grown fetuses the pulsatility index values significantly decreased with advancing gestation. In growth-retarded fetuses the pulsatility index values were significantly elevated compared to those of normal fetuses. A significant relationship was observed between the severity of hypoxia and pulsatility index values from the peripheral pulmonary arteries in 29 fetuses in which Doppler recordings were obtained immediately before cordocentesis. In conclusion, these data show that in normal fetuses the Doppler-measured impedance to flow in the peripheral pulmonary circulation decreases with advancing gestation. Impedance to flow in the lungs is elevated in the presence of growth retardation and this increase is related to the severity of fetal hypoxia.

Acid-Base Equilibrium↗

Evidence of strategic effects in the modulation of orienting of attention.

Two models of visual orienting of attention are frequently described. Voluntary orienting is usually induced by central cues that direct subjects' attention to a given location in the visual space. Automatic orienting is provoked by presentation of peripheral cues. It is shown that automatic orienting induces greater attentional costs and benefits, and is less under a subject's control (Jonides 1981). Furthermore, it is not similarly affected by factors such as signal eccentricity (Umiltà et al. 1991). The present experiment was undertaken to investigate how sensitive automatic orienting produced by peripheral cues is to voluntary modulations of attention. In experiment 1, subjects facing situations daily in which attentional requirements are high, were compared to non-practiced ones. In experiment 2, other groups of practiced subjects facing high or low attentional-demanding situations were tested. In both experiments, subjects were asked to respond to signals, presented in rapid succession, in one of two possible locations in space, on each side of central fixation point. The cue signal automatically oriented attention to one of the two locations in which a first stimulus was presented with 100% probability; 100 ms after the first response (RT1), a second response signal (RT2) was delivered either in the same location (valid condition) or in the opposite location (invalid condition). Four cue probabilities were manipulated for this second stimulus: 100%/0%, 80%/20%, 50%/50%, and 20%/80%. Two eccentricities of 3 degrees and 6 degrees were tested. RT2 data demonstrated that (1) there was no eccentricity effect; (2) the higher the cue probability, the greater were the attentional costs; (3) the attentional effects were smaller in the practiced subjects who faced attention-demanding situations daily, than in the other groups. Put together, these data suggest that automatic orienting of attention can be modulated by voluntary attentional processes, according to cue probability. Furthermore, experienced subjects seem to be able to better distribute their attentional resources in space, with increased task requirements. The adoption of an optimal criterion might lead to the use of a cost minimizing strategy.

Adult↗

[Functional aspects of the fetal urinary apparatus in relation to growth].

The normal and regular development of the fetal renal function is related to fetal growth and to the correct development of the fetal lung. Besides, the fetal kidneys plays an important role in the regulation of the hydro-electrolytic balance and in the modulation of the fetal arterial pressure. The postnatal renal failure is one of the most dangerous factors which may occur in the very small preterm babies (birth weight below 1000 g) and their therapeutical answer depends on the degree of kidney maturation. The knowledge of the kidney maturation process is one of the actual controversies in perinatal medicine. The development of the renal nephron and of the excretory system continues until 32-36 weeks of gestation, their maturation process ends only some months after birth. At 9 weeks of gestation the embryonic kidney may be seen in a transvaginal ultrasonographic scanning; the calico-pelvic system is visible from the 11th week of gestation and the bladder may be seen by ultrasound from the 12 weeks' gestation. The fetal glomerular ultrafiltration process starts at the 10-11 week of gestation and the most important factors that improve the volume of glomerular ultrafiltrate is the total renal mass which is related to the number of functional nephron units. The Doppler velocimetry performed on the fetal renal artery has shown that the fetal renal blood flow increases with the increase of the renal volume and gestational age and it depends on the cardiac output. In the renal artery the resistance to blood flow decreases with gestational age. During fetal hypoxia there is a reduction of the amniotic fluid production; this phenomenon is related to the redistribution of the fetal blood flow with a decrease of the perfusion of peripheric organs (as the kidney) and an increase of the perfusion of brain, heart, liver and adrenals. The hypoxic fetal kidney is ischemic; moreover, the urine production rate is diminished and the humoral response of the kidney increase the fetal arterial pressure which maintains the haemodynamic compensation to hypoxia. When this situation is prolonged, there is possibly renal failure. The fetal renal ultrasonographic examination can give important information about the maturity degree of the fetal kidney and the evaluation of Doppler velocimetry on renal artery and the evaluation of the amniotic fluid allow the monitoring of fetal hypoxia. In future the Doppler velocimetry of intrarenal arteries and the biochemical evaluation of the amniotic fluid may a real evaluation of the fetal renal function.

Adult↗

cAMP-dependent SOS induction and mutagenesis in resting bacterial populations.

The inducible SOS system increases the survival of bacteria exposed to DNA-damaging agents by increasing the capacity of error-free and error-prone DNA repair systems. The inducible mutator effect is expected to contribute to the adaptation of bacterial populations to these adverse life conditions by increasing their genetic variability. The evolutionary impact of the SOS system would be even greater if it was also induced under conditions common in nature, such as in resting bacterial populations. The results presented here show that SOS induction and mutagenesis do occur in bacteria in aging colonies on agar plates. The observed SOS induction and mutagenesis are controlled by the LexA repressor and are RecA- and cAMP-dependent.

Bacterial Proteins↗

Editing DNA replication and recombination by mismatch repair: from bacterial genetics to mechanisms of predisposition to cancer in humans.

A hereditary form of colon cancer, hereditary non-polyposis colon cancer (HNPCC), is characterized by high instability of short repeated sequences known as microsatellites. Because the genes controlling microsatellite stability were known in bacteria and yeast, as was their evolutionary conservation, the search for human genes responsible for HNPCC became a 'targeted' search for known sequences. Mismatch-repair deficiency in bacteria and yeast produces multiple phenotypes as a result of its dual involvement in the editing of both replication errors and recombination intermediates. In addition, mismatch-repair functions are specialized in eukaryotes, characterized by specific mitotic (versus meiotic) functions, and nuclear (versus mitochondrial) localization. Given the number of phenotypes observed so far, we predict other links between mismatch-repair deficiency and human genetic disorders. For example, a similar type of sequence instability has been found in HNPCC tumours and in a number of neuro-muscular genetic disorders. Several human mitochondrial disorders display genomic instabilities reminiscent of yeast mitochondrial mismatch-repair mutants. In general, the process of mismatch repair is responsible for the constant maintenance of genome stability and its faithful transmission from one generation to the next. However, without genetic alteration, species would not be able to adapt to changing environments. It appears that nature has developed both negative and positive controls for genetic diversity. In bacteria, for example, an inducible system (sos) exists which generates genetic alterations in response to environmental stress (e.g. radiation, chemicals, starvation). Hence, the cost of generating diversity to adapt to changing conditions might be paid as sporadic gene alterations associated with disease.

Amino Acid Sequence↗

[Doppler echocardiographic analysis of blood flow through the fetal aorta and pulmonary valve in the second half of pregnancy].

Pulsed Doppler velocimetry of the fetal aortic and pulmonary valves derived in the five-chamber-view and short-axis view were performed in 88 uncomplicated pregnancies between the 20th and 40th week of gestation. The maximal and mean velocities were assessed for both semilunar valves. Considering the valve diameters and heart rate the stroke volume and cardiac output for both ventricles were calculated. Furthermore, the common stroke volume, common cardiac output and the ratio of right to left cardiac output were calculated. Normal ranges for all these parameters were constructed and correlated with gestational age. The maximal velocities were higher in the aorta than in the pulmonary trunk, but no differences were found in the mean velocities. The stroke volume and cardiac output of the right ventricle were in higher ratio 1.3:1 than that of the left ventricle as an expression of the right ventricular dominance in the fetus. Intracardiac Doppler flow velocimetry gives an insight into the physiology of fetal circulation and is a basis for the analysis of blood flow under pathological conditions.

Aorta↗

Tumor necrosis factor alpha induces apoptosis in mammary adenocarcinoma cells by an increase in intranuclear free Ca2+ concentration and DNA fragmentation.

The incubation of human mammary adenocarcinoma cells (BT-20) with tumor necrosis factor alpha in the absence or presence of cycloheximide resulted in progressive DNA fragmentation. This was preceded by a sustained increase in intracellular free Ca2+ concentration and was not detected in cells pretreated with intracellular Ca2+ chelators, calmodulin antagonists, or activators of protein kinase C. Image analysis of fura-2-loaded BT-20 cells treated with tumor necrosis factor alpha revealed that, in many cells, the initial increase in Ca2+ level occurred in a cellular region that corresponded to the localization of the nucleus. Our findings suggest that tumor necrosis factor alpha can promote an increase in intranuclear free Ca2+ which, in turn, may stimulate Ca(2+)-dependent endonuclease activity, resulting in DNA fragmentation and apoptosis.

Adenocarcinoma↗

Acute effects of intravenous phosphodiesterase inhibition in chronic heart failure: simultaneous pre- and afterload reduction with a single agent.

Intravenous phosphodiesterase inhibition with milrinone is known to have a beneficial effect on haemodynamics in chronic heart failure. Its effect on lower limb capacitance vessels has not been previously investigated. We have studied the effect of intravenous milrinone in 10 patients with severe chronic heart failure. Thirty minutes after commencement of treatment mean cardiac index had risen by 26% and pulmonary artery wedge pressure, systemic vascular resistance and right atrial pressure had fallen by 51, 24 and 89%, respectively (p less than 0.05 for all changes). These changes were maintained for the 2 h observation period with no evidence of tolerance and were accompanied by a 17% increase in venous volume (p less than 0.01) and a 42% increase in ejection fraction (p less than 0.001) at 30 min; at 120 min the improvement in ejection fraction had been maintained and a further increase in venous volume to 38% above baseline was evident. The increase in venous volume was strongly correlated with the decrease in mean pulmonary artery wedge pressure and mean right atrial pressure at 30 min and 2 h (r = -0.80 and -0.69 for mean pulmonary artery wedge pressure, r = -0.88 and -0.56 for mean right atrial pressure). Milrinone therefore has clinically important venodilating properties, in addition to its known effects as an arterial vasodilator and a positive inotrope.

Aged↗