Background: Previous work from our laboratory showed that (i) vertebrate genomes are mosaics of isochores, typically megabase-size DNA segments that are fairly homogeneous in base composition; (ii) isochores belong to a small number of families (five in the human genome) characterized by different GC levels; (iii) isochore family patterns are different in fishes/amphibians and mammals/birds, the latter showing GC-rich isochore families that are absent or very scarce in the former; (iv) there are two modes of genome evolution, a conservative one in which isochore patterns basically do not change (e.g., among mammalian orders), and a transitional one, in which they do change (e.g., between amphibians and mammals); and (v) isochores are tightly linked to a number of basic biological properties, such as gene density, gene expression, replication timing and recombination. Results: The present availability of a number of fully sequenced genomes ranging from fishes to mammals allowed us to carry out investigations that (i) more precisely quantified our previous conclusions; (ii) showed that the different isochore families of vertebrate genomes are largely conserved in GC levels and dinucleotide frequencies, as well as in isochore size; and (iii) isochore family patterns can be either conserved or change within both warm- and cold-blooded vertebrates. Conclusion: On the basis of the results presented, we propose that (i) the large conservation of GC levels and dinucleotide frequencies may reflect the conservation of chromatin structures; (ii) the conservation of isochore size may be linked to the role played by isochores in chromosome structure and replication; (iii) the formation, the maintainance and the changes of isochore patterns are due to natural selection.
Sirtuins genes are widely distributed by evolution and have been found in eubacteria, archaea and eukaryotes. While prokaryotic and archeal species usually have one or two sirtuin homologs, in humans as well as in eukaryotes we found multiple versions and in mammals this family is comprised of seven different homologous proteins being all NAD-dependent de-acylases. 3D structures of human SIRT2, SIRT3, and SIRT5 revealed the overall conformation of the conserved core domain but they were unable to give a structural information about the presence of very flexible and dynamically disordered regions, the role of which is still structurally and functionally unclear. Recently, we modeled the 3D-structure of human SIRT1, the most studied member of this family, that unexpectedly emerged as a member of the intrinsically disordered proteins with its long disordered terminal arms. Despite clear similarities in catalytic cores between the human sirtuins little is known of the general structural characteristics of these proteins. The presence of disorder in human SIRT1 and the propensity of these proteins in promoting molecular interactions make it important to understand the underlying mechanisms of molecular recognition that reasonably should involve terminal segments. The mechanism of recognition, in turn, is a prerequisite for the understanding of any functional activity. Aim of this work is to understand what structural properties are shared among members of this family in humans as well as in other organisms.
Enzymes play key roles in different cellular processes, for example, in signal transduction, cell differentiation and proliferation, metabolic processes, DNA damage repair, apoptosis, and response to stress. A deregulation of enzymes has been considered one of the first causes of several diseases, including cancers. In the last several years, enzyme inhibitors, being good candidates as drugs in the pathogenic processes, have received an increasing amount of attention for their potential application in pharmacology. The marine environment is considered a challenging source of enzyme inhibitors for pharmacological applications. In this review, we report on secondary metabolites with enzyme inhibitory activity, focusing our attention on marine sponges and bacteria as promising sources. In the case of sponges, we only reported the kinase inhibitors, because this class was the most representative isolated so far from these marine organisms.
Previous investigations from our laboratory were largely focused on the genome organization of vertebrates. We showed that these genomes are mosaics of isochores, megabase-size DNA sequences that are fairly homogeneous in base composition yet belong to a small number of families that cover a wide compositional spectrum. A question raised by these results concerned how far back in evolution an isochore organization of the eukaryotic genome arose.
Diatoms are unicellular eukaryotic organisms that play a key ecological and biogeochemical role in oceans as major primary producers. Recently, these microalgae have also attracted interest as a promising source of functional products with widespread relevance. Progress in the knowledge of cell and molecular biology of diatoms is envisaged as a key step to understanding regulation of their life cycle in marine environments as well as facilitating their full and profitable exploitation by biotechnological platforms. Recently, we identified sterol sulfates (StS) as regulatory molecules of cell death in the diatom Skeletonema marinoi. As these compounds may have a general role in diatom physiology and chemical signals in aquatic systems, we investigated a suitable tool for their analysis in laboratory and field samples. Herein, we describe a sensitive, fast, and efficient ultra performance liquid chromatography–mass spectrometry (UPLC–MS) method for qualitative and quantitative analysis of StS from crude extract of diatoms and other microalgae. The method was applied to 13 different strains of our collection of marine protists. This first study suggested a species-specific distribution of StS and identified the sulfated derivatives of 24-methylene cholesterol and 24-methyl cholesterol as the most common members in diatoms.