p53 Suppression partially rescues the mutant phenotype in mouse models of DiGeorge syndrome.

T-box 1 (Tbx1), a gene encoding a T-box transcription factor, is required for embryonic development in humans and mice. Half dosage of this gene in humans causes most of the features of the DiGeorge or Velocardiofacial syndrome phenotypes, including aortic arch and cardiac outflow tract abnormalities. Here we found a strong genetic interaction between Tbx1 and transformation related protein 53 (Trp53).

Incontinentia pigmenti: report on data from 2000 to 2013.

We report here on the building-up of a database of information related to 386 cases of Incontinentia Pigmenti collected in a thirteen-year activity (2000-2013) at our centre of expertise. The database has been constructed on the basis of a continuous collection of patients (27.6/year), the majority diagnosed as sporadic cases (75.

Cripto haploinsufficiency affects in vivo colon tumor development.

Colorectal cancer is one of the most common and aggressive cancers arising from alterations in various signaling pathways, such as the WNT, RAS-MAPK, PI3K and transforming growth factor-β (TGF-β) pathways. Cripto (also called Teratocarcinoma-derived growth factor), the original member of the vertebrate EGF-CFC family, plays a key role in all of these pathways and is deeply involved in early embryo development and cancer progression. The role of Cripto in colon and breast cancer, in particular, has been investigated, as it is still not clearly understood.

Identification of NuRSERY, a new functional HDAC complex composed by HDAC5, GATA1, EKLF and pERK present in human erythroid cells.

To clarify the role of HDACs in erythropoiesis, expression, activity and function of class I (HDAC1, HDAC2, HDAC3) and class IIa (HDAC4, HDAC5) HDACs during in vitro maturation of human erythroblasts were compared. During erythroid maturation, expression of HDAC1, HDAC2 and HDAC3 remained constant and activity and GATA1 association (its partner of the NuRD complex), of HDAC1 increased. By contrast, HDAC4 content drastically decreased and HDAC5 remained constant in content but decreased in activity.

Insight into IKBKG/NEMO locus: report of new mutations and complex genomic rearrangements leading to incontinentia pigmenti disease.

Incontinentia pigmenti (IP) is an X-linked-dominant Mendelian disorder caused by mutation in the IKBKG/NEMO gene, encoding for NEMO/IKKgamma, a regulatory protein of nuclear factor kappaB (NF-kB) signaling. In more than 80% of cases, IP is due to recurrent or nonrecurrent deletions causing loss-of-function (LoF) of NEMO/IKKgamma. We review how the local architecture of the IKBKG/NEMO locus with segmental duplication and a high frequency of repetitive elements favor de novo aberrant recombination through different mechanisms producing genomic microdeletion.

De novo DNMTs and DNA methylation: novel insights into disease pathogenesis and therapy from epigenomics.

DNA methylation plays an important role in epigenetics signaling, having an impact on gene regulation, chromatin structure and development. Within the family of de novo DNA methyltransferases two active enzymes, DNMT3A and DNMT3B, are responsible for the establishment of the proper cytosine methylation profile during development. Defects in DNMT3s function correlate with pathogenesis and progression of monogenic diseases and cancers.

The origin of the genetic code in the ocean abysses: new comparisons confirm old observations.

I have analysed the amino acid substitution pattern between two pairs of nonbarophilic-barophilic organisms in order to confirm previous results. Indeed, the pattern deriving from a different pair of such organisms led to establish that the origin of the genetic code might have occurred in the ocean abysses. The hydrostatic pressure asymmetry indices computable from these matrices of amino acid substitutions confirm the correlation previously observed, even when differences in GC content are accounted for.

A polyphyletic model for the origin of tRNAs has more support than a monophyletic model.

The monophyletic and polyphyletic origins of tRNAs are compared. The monophyletic hypothesis of the origin of the tRNA molecule would turn out to be strictly true only if a universal tRNA, possessing a number of anticodons with which to read primitive mRNAs, was present at the Last Universal Common Ancestor (LUCA) stage. On the other hand, whether a tRNA precursor less complex than it - for instance a hairpin - was present at the LUCA stage, then one should imperatively predict a phase of evolutionary convergence towards the cloverleaf structure typical of tRNAs, equivalent to a polyphyletic origin, also in presence of a real monophyletic origin.

The discovery of placenta growth factor and its biological activity.

Angiogenesis is a complex biological phenomenon crucial for a correct embryonic development and for post-natal growth. In adult life, it is a tightly regulated process confined to the uterus and ovary during the different phases of the menstrual cycle and to the heart and skeletal muscles after prolonged and sustained physical exercise. Conversly, angiogenesis is one of the major pathological changes associated with several complex diseases like cancer, atherosclerosis, arthritis, diabetic retinopathy and age-related macular degeneration.

Genomic architecture at the Incontinentia Pigmenti locus favours de novo pathological alleles through different mechanisms.

IKBKG/NEMO gene mutations cause an X-linked, dominant neuroectodermal disorder named Incontinentia Pigmenti (IP). Located at Xq28, IKBKG/NEMO has a unique genomic organization, as it is part of a segmental duplication or low copy repeat (LCR1-LCR2, >99% identical) containing the gene and its pseudogene copy (IKBKGP). In the opposite direction and outside LCR1, IKBKG/NEMO partially overlaps G6PD, whose mutations cause a common X-linked human enzymopathy.

A nonsynonymous TNFRSF11A variation increases NFκB activity and the severity of Paget's disease.

Mutations in the SQSTM1 gene were identified as a common cause of Paget's disease of bone (PDB) but experimental evidence demonstrated that SQSTM1 mutation is not sufficient to induce PDB in vivo. Here, we identified two nonsynonymous single nucleotide polymorphisms (SNPs) (C421T, H141Y and T575C, V192A) in the TNFRSF11A gene, associated with PDB and with the severity of phenotype in a large population of 654 unrelated patients that were previously screened for SQSTM1 gene mutations. The largest effect was found for the T575C variant, yielding an odds ratio of 1.

piR_015520 belongs to Piwi-associated RNAs regulates expression of the human melatonin receptor 1A gene.

Piwi-associated RNAs (piRNAs) are a distinct class of 24- to 30-nucleotide-long RNAs produced by a Dicer-independent mechanism, and are associated with Piwi-class Argonaute proteins. In contrast to the several hundred species of microRNAs (miRNAs) identified thus far, piRNAs consist of more than 30,000 different species in humans. Studies in flies, fish and mice implicate these piRNAs in regulating germ line development, the silencing of selfish DNA elements, and maintaining germ line DNA integrity.

The last universal common ancestor (LUCA) and the ancestors of archaea and bacteria were progenotes.

The tRNA split genes of Nanoarchaeum equitans and the Met-tRNA(fMet) → fMet-tRNA(fMet) pathway, identifiable as ancestral traits, and the late appearance of DNA are used to understand the evolutionary stage at which the progenote → genote transition took place. The arguments are such as to impose that not only was the last universal common ancestor (LUCA) a progenote, but the ancestors of Archaea and Bacteria were too. Therefore, the progenote → genote transition took place in a very advanced stage of the evolution of the tree of life, and only when the ancestors of Archaea and Bacteria were already defined.

PPARG: Gene Expression Regulation and Next-Generation Sequencing for Unsolved Issues.

Peroxisome proliferator-activated receptor gamma (PPARγ) is one of the most extensively studied ligand-inducible transcription factors (TFs), able to modulate its transcriptional activity through conformational changes. It is of particular interest because of its pleiotropic functions: it plays a crucial role in the expression of key genes involved in adipogenesis, lipid and glucid metabolism, atherosclerosis, inflammation, and cancer. Its protein isoforms, the wide number of PPARγ target genes, ligands, and coregulators contribute to determine the complexity of its function.

Biological evidence against the panspermia theory.

The following idea is analysed. Given that evolution on Earth seems to have passed through protocellular evolutionary stages of progenotes, this would appear to be incompatible with the panspermia theory because this observation would imply that the infection bringing life to the Earth started in these protocells, for which a low or null infective power is generally expected.

Nutritional genomics era: opportunities toward a genome-tailored nutritional regimen.

There is increasing evidence indicating that nutritional genomics represents a promise to improve public health. This goal will be reached by highlighting the mechanisms through which diet can reduce the risk of monogenic and common polygenic diseases. Indeed, nutrition is a very relevant environmental factor involved in the development and progression of metabolic disorders, as well as other kind of diseases.

Formal proof that the split genes of tRNAs of Nanoarchaeum equitans are an ancestral character.

A proof is given that the genes of the tRNA molecule of Nanoarchaeum equitans split into the 5' and 3' halves are an ancestral trait. First, the existence of a natural succession of evolutionary stages will be proven, formed in the order of the three gene structures of tRNAs known today: (i) the split genes of tRNAs, (ii) the genes of tRNAs with introns, and (iii) the genes of tRNAs continuously codifying for the tRNA molecule. This succession of evolutionary stages identifies the split genes of tRNAs as a pleisiomorphic character.

Microdeletion/duplication at the Xq28 IP locus causes a de novo IKBKG/NEMO/IKKgamma exon4_10 deletion in families with Incontinentia Pigmenti.

The Incontinentia Pigmenti (IP) locus contains the IKBKG/NEMO/IKKgamma gene and its truncated pseudogene copy, IKBKGP/deltaNEMO. The major genetic defect in IP is a heterozygous exon4_10 IKBKG deletion (IKBKGdel) caused by a recombination between two consecutive MER67B repeats. We analyzed 91 IP females carrying the IKBKGdel, 59 of whom carrying de novo mutations (65%).

A methanogen hosted the origin of the genetic code.

A comparison is made between orthologous proteins from a methanogen (Methanopyrus kandleri) and from a non-methanogen (Pyrococcus abyssi) in order to determine the amino acid substitution pattern. This analysis makes it possible to establish which amino acids are significantly and asymmetrically utilised by these two organisms. A methanophily index (MI) based on this asymmetry makes it possible for any protein to be associated with a numerical value which, when calculated for the same orthologous protein from methanogenic and non-methanogenic organisms, turns out to have the power to discriminate between these two groups of organisms, even if only for about 20% of the analysed proteins.

The close relationship between the biosynthetic families of amino acids and the organisation of the genetic code.

By generating random codes and applying Fisher's exact test, we confirm that the biosynthetic families of amino acids are intimately involved in the organisation of the genetic code. This observation corroborates the coevolution theory of genetic code origin. As the amino acids belonging to the single biosynthetic families have codons that are contiguous in the genetic code, they must have entered the code itself by means of a clustering mechanism, which must clearly have been compatible with the mechanism on which this theory is based because this too envisages the clustering of biosynthetically correlated amino acids within the code.

An extension of the coevolution theory of the origin of the genetic code.

Background: The coevolution theory of the origin of the genetic code suggests that the genetic code is an imprint of the biosynthetic relationships between amino acids. However, this theory does not seem to attribute a role to the biosynthetic relationships between the earliest amino acids that evolved along the pathways of energetic metabolism. As a result, the coevolution theory is unable to clearly define the very earliest phases of genetic code origin.

The origin of genes could be polyphyletic.

The paradigm of the monophyletic origin of genes is deeply rooted in us all. For instance, this stems from the observation that the possibility of obtaining a good multiple alignment using the same protein from organisms from the three domains of life (Bacteria, Archaea and Eukarya) would seem to imply that the last universal common ancestor (LUCA) must have had that protein and, therefore, the origin of that gene must necessarily be monophyletic. The hypothesis of a polyphyletic origin of genes has to explain how it was possible to evolve highly conserved regions of multiple alignments of orthologous proteins from the three domains of life when these regions clearly seem to define a monophyletic origin of genes.