Biomedical subjects

Lucia Pappalardo

Publications and source records attributed to Lucia Pappalardo.

5 recordsLinked to original sources

PubMed2006

Prematurity may be a risk factor for thyroid dysfunction in childhood.

CONTEXT: Children born prematurely and/or small for gestational age (SGA) frequently show disturbances in thyroid function. OBJECTIVE: The objective of the study was to determine the role played either by size or gestational age on subsequent thyroid function. DESIGN AND SETTING: This cross-sectional study was conducted at a tertiary referral hospital. PATIENTS: A total of 117 children, 88 of whom were SGA (mean age 7.8 +/- 2.5 yr) and 29 appropriate for gestational age (AGA) (mean age 8.1 +/- 1.9 yr), were selected for the study. MAIN OUTCOME MEASURES: We evaluated TSH, free T(4), free T(3), urinary iodine, and antithyroid antibodies, and all patients underwent a thyroid ultrasound. Insulin sensitivity was assessed with the quantitative insulin sensitivity check index. RESULTS: TSH and free T3 were not significantly different in the two groups, whereas free T4 was higher in the AGA group (P < 0.005). Interestingly, four AGA (13.8%) and 17 SGA (19.3%) patients had TSH levels above the upper limit of normality. Thyroid volume was normal and thyroid autoimmunity was excluded. Urinary iodine was also similar in the two groups (115 +/- 66 vs. 143 +/- 87); however, in both groups there were some children [15 AGA (51%) and 13 SGA (14.7%) (P < 0.001)] with a mild to moderate iodine deficiency. By multiple regression analysis, gestational age was found to be the only determinant of TSH serum levels. Insulin sensitivity was the same in both groups of children and similar to controls. CONCLUSIONS: Some children born prematurely, independently from their birth size, frequently have disturbances of the hypothalamus-pituitary-thyroid axis later in life.

Body Mass Index↗

PubMed2006

The Avellino 3780-yr-B.P. catastrophe as a worst-case scenario for a future eruption at Vesuvius.

A volcanic catastrophe even more devastating than the famous anno Domini 79 Pompeii eruption occurred during the Old Bronze Age at Vesuvius. The 3780-yr-B.P. Avellino plinian eruption produced an early violent pumice fallout and a late pyroclastic surge sequence that covered the volcano surroundings as far as 25 km away, burying land and villages. Here we present the reconstruction of this prehistoric catastrophe and its impact on the Bronze Age culture in Campania, drawn from an interdisciplinary volcanological and archaeoanthropological study. Evidence shows that a sudden, en masse evacuation of thousands of people occurred at the beginning of the eruption, before the last destructive plinian column collapse. Most of the fugitives likely survived, but the desertification of the total habitat due to the huge eruption size caused a social-demographic collapse and the abandonment of the entire area for centuries. Because an event of this scale is capable of devastating a broad territory that includes the present metropolitan district of Naples, it should be considered as a reference for the worst eruptive scenario at Vesuvius.

Journal Article↗

PubMed2005

The preferred conformation of the tripeptide Ala-Phe-Ala in water is an inverse gamma-turn: implications for protein folding and drug design.

Recent studies have provided evidence that peptides as short as tripeptides do adopt preferred conformations. Here we report that the tripeptide Ala-Phe-Ala (AFA) in aqueous solution preferentially forms an inverse gamma-turn. Circular dichroism (CD) indicated the presence of a predominant turn structure, and Fourier transform infrared (FTIR) bands suggested the presence of a gamma-turn forming a bifurcated H-bond with the solvent molecules. The high-resolution structure was obtained by a combined use of NMR spectroscopy and calculations. On the basis of 30 unambiguous ROESY-derived distance restraints (including the Halpha-NH NOE between Ala(1) and Ala(3) and a hydrogen bond between the CO group of Ala(1) and the NH group of Ala(3)), calculations clearly demonstrated the presence of an inverse gamma-turn centered on Phe(2). From NOE data, we estimated a mole fraction for the gamma-turn of 0.65. Since for AFA an extended beta-strand was also reported [Eker, F., Griebenow, K., Cao, X., Nafie, L. A., and Schweitzer-Stenner, R. (2004) Proc. Natl. Acad. Sci. U.S.A. 101, 10054-10059], we investigated the possibility that gamma-turn and beta-strand may represent two major conformations. By using a best-fit procedure that calculated experimental NOEs as weighted averages of the effects originating from both structures, we were able to calculate with good accuracy the backbone NOEs at 280 K in terms of the two limiting conformers, yielding a mole fraction for the gamma-turn and beta-strand conformations of 0.60 and 0.40, respectively, in good agreement with those found by NOE data. The implication of the existence of a preferred conformation by a small structural element is discussed in the context of the nucleation of protein folding events and the design of small peptide and peptidomimetic drugs.

Alanine↗

PubMed2004

Enhancement by effectors and substrate nucleotides of R1-R2 interactions in Escherichia coli class Ia ribonucleotide reductase.

Ribonucleotide reductases are a family of essential enzymes that catalyze the reduction of ribonucleotides to their corresponding deoxyribonucleotides and provide cells with precursors for DNA synthesis. The different classes of ribonucleotide reductase are distinguished based on quaternary structures and enzyme activation mechanisms, but the components harboring the active site region in each class are evolutionarily related. With a few exceptions, ribonucleotide reductases are allosterically regulated by nucleoside triphosphates (ATP and dNTPs). We have used the surface plasmon resonance technique to study how allosteric effects govern the strength of quaternary interactions in the class Ia ribonucleotide reductase from Escherichia coli, which like all class I enzymes has a tetrameric alpha(2) beta(2) structure. The component alpha(2)called R1 harbors the active site and two types of binding sites for allosteric effector nucleotides, whereas the beta(2) component called R2 harbors the tyrosyl radical necessary for catalysis. Our results show that only the known allosteric effector nucleotides, but not non-interacting nucleotides, promote a specific interaction between R1 and R2. Interestingly, the presence of substrate together with allosteric effector nucleotide strengthens the complex 2-3 times with a similar free energy change as the mutual allosteric effects of substrate and effector nucleotide binding to protein R1 in solution experiments. The dual allosteric effects of dATP as positive allosteric effector at low concentrations and as negative allosteric effector at high concentrations coincided with an almost 100-fold stronger R1-R2 interaction. Based on the experimental setup, we propose that the inhibition of enzyme activity in the E. coli class Ia enzyme occurs in a tight 1:1 complex of R1 and R2. Most intriguingly, we also discovered that thioredoxin, one of the physiological reductants of ribonucleotide reductases, enhances the R1-R2 interaction 4-fold.

Allosteric Regulation↗

PubMed2003

The NMR structure of the sensory domain of the membranous two-component fumarate sensor (histidine protein kinase) DcuS of Escherichia coli.

The structure of the water-soluble, periplasmic domain of the fumarate sensor DcuS (DcuS-pd) has been determined by NMR spectroscopy in solution. DcuS is a prototype for a sensory histidine kinase with transmembrane signal transfer. DcuS belongs to the CitA family of sensors that are specific for sensing di- and tricarboxylates. The periplasmic domain is folded autonomously and shows helices at the N and the C terminus, suggesting direct linking or connection to helices in the two transmembrane regions. The structure constitutes a novel fold. The nearest structural neighbor is the Per-Arnt-Sim domain of the photoactive yellow protein that binds small molecules covalently. Residues Arg107, His110, and Arg147 are essential for fumarate sensing and are found clustered together. The structure constitutes the first periplasmic domain of a two component sensory system and is distinctly different from the aspartate sensory domain of the Tar chemotaxis sensor.

Amino Acid Sequence↗