The signature of long-standing balancing selection at the human defensin β-1 promoter

Analysis of the human beta defensin 1 promoter region in six human populations reveals a signature of balancing selection

Both selective and neutral processes drive GC content evolution in the human genome

<p>Abstract</p> <p>Background</p> <p>Mammalian genomes consist of regions differing in GC content, referred to as isochores or GC-content domains. The scientific debate is still open as to whether such compositional heterogeneity is a selected or neutral trait.</p> <p>Results</p> <p>Here we analyze SNP allele frequencies, retrotransposon insertion polymorphisms (RIPs), as well as fixed substitutions accumulated in the human lineage since its divergence from chimpanzee to indicate that biased gene conversion (BGC) has been playing a role in within-genome GC content variation. Yet, a distinct contribution to GC content evolution is accounted for by a selective process. Accordingly, we searched for independent evidences that GC content distribution does not conform to neutral expectations. Indeed, after correcting for possible biases, we show that intron GC content and size display isochore-specific correlations.</p> <p>Conclusion</p> <p>We consider that the more parsimonious explanation for our results is that GC content is subjected to the action of both weak selection and BGC in the human genome with features such as nucleosome positioning or chromatin conformation possibly representing the final target of selective processes. This view might reconcile previous contrasting findings and add some theoretical background to recent evidences suggesting that GC content domains display different behaviors with respect to highly regulated biological processes such as developmentally-stage related gene expression and programmed replication timing during neural stem cell differentiation.</p

Il Complesso funerario di Neferhotep (Luxor): una lunga storia di ‘riutilizzi’. Progetto, metodologie, tecnologie, scavo e protocolli archeometrici integrati

AbstractThe project is focusing on a monumental funerary complex which is located in the Valley of the Nobles at Luxor. The topographic context is certainly very interesting, both because it is not very well known and deeply investigated, as well as because it appears to have been densely exploited in antiquity and for long time. It was then intensively inhabited in the last two centuries, fact that determined the obliteration ofnumerous tombs, but also the loss of the sense of context of this section of the ancient necropolis of Luxor. It was certainly in antiquity an important section of the necropolis, looking at the monumentality of some of the tombs, and it has been continuously used for centuries for funerarypurposes, not only during the “pharaonic period”, but also during later periods, as clearly suggested by Ptolemaic tombs, Greco-Roman inscriptions and finds. A large team is collaborating at the project, including very different scholars and senior students working together from the excavation to the topographic survey, from the diagnostic apping to the conservation, from the anthropometric analysis to the archaeometric studies, from the epigraphic interpretation to the historical reconstruction. A multidisciplinary approach to the study of this funerary complex can guarantee both an interdisciplinary interpretation of the monuments, as well as of their evolution and use throughout a long period.Too often, in fact, the monuments in Egypt are analysed just looking at their original plan and use in the pharaonic period; nevertheless, in the Theban necropolis the interesting phenomenon of the ‘re-use’ iswidely attested, and the tombs present frequent enlargements, later openings, junctions with neighbor tombs, later passages transforming the original plans.The Neferhotep’s Complex represents one of the most interesting in this sense because about six tombs have been built around a large courtyard in the late Bronze period, but about three more phases are clearly attested now by the new excavations and surveys, showing that also in the ‘later periods’, from the 7th to the 1st centuries BC, the tombs in this complex were continuously reused for burials and widely reorganized, transforming slowly their original shapes. In Roman times, the presence of the legions in the area, has determined a partial change of use of some of the areas of the necropolis, while some other contexts have continued to be used for funerary purposes.The plan of the funerary complex is quite articulated (fig.1), with a central square courtyard, crowning and emphasizing the larger tomb, which is known as TT49. It was built just at the end of the XVIII dynasty and still preserves the original spectacular paintings. The conservation of the decorations is based on the use of a non-invasive laser methodology. A German team (PROCON) is conservating the tomb, and within the last eight seasons a large portion of the paintings in the funerary chapel have been completely cleaned and consolidated.An equip of Egyptologists, both Argentinian (the University of Buenos Aires and the CONICET) and Brasilian (of the National Museum of Rio de Janeiro) is studying and interpreting hieroglyphics and iconographies. Moreover, a team of archaeologists, geologists and topographers from the University of Chieti is working at the excavations of other two tombs of this architectonic complex and at the mapping of the context and of the tombs. During the last seasons also a team of anthropologists and palaeo-botanists from the Museum of Chieti University has joined the team, especially because of the large quantity of human and organic remains coming from the excavations. The aim of this paper is to present the project, its interdisciplinary methodologies and the preliminary results of the last seasons. Moreover, the complex is presented here analyzing not only the main original tombs and monuments, but including the numerous phases through the centuries till recent times.

Loggerhead Sea Turtle as Possible Source of Transmission for Zoonotic Listeriosis in the Marine Environment

Listeria monocytogenes is an ubiquitous pathogen isolated from different host species including fish, crustaceans, and molluscs, but it is rarely a pathogenic microorganism to marine reptiles. In particular, only two cases of fatal disseminated listeriosis have been described in the loggerhead sea turtle (Caretta caretta). In this study, we describe a lethal case of L. monocytogenes infection in a loggerhead sea turtle. The turtle was found alive, stranded on a beach in North-eastern Italy, but perished soon after being rescued. The autoptic examination revealed that heart, lung, liver, spleen, and urinary bladder were disseminated with multiple, firm, 0.1–0.5 mm sized, nodular, white-green lesions. Microscopically, these lesions corresponded with heterophilic granulomas with Gram+ bacteria within the necrotic center. Furthermore, the Ziehl–Neelsen stain was negative for acid-fast organisms. Colonies isolated from heart and liver were tested through MALDI-TOF for species identification, revealing the presence of L. monocytogenes. Whole Genome Sequencing on L. monocytogenes isolates was performed and the subsequent in silico genotyping revealed the belonging to Sequence Type 6 (ST 6); the virulence profile was evaluated, showing the presence of pathogenicity islands commonly observed in ST 6. Our results further confirm that L. monocytogenes should be posed in differential diagnosis in case of nodular lesions of loggerhead sea turtles; thus, given the zoonotic potential of the microorganism, animals should be treated with particular caution. In addition, wildlife animals can play an active role as carriers of possibly pathogenetic and virulent strains and contribute to the distribution of L. monocytogenes in the environment

A dynamic system analysis of dyadic flexibility and stability across the Face-to-Face Still-Face procedure: application of the State Space Grid

The Face-to-Face Still-Face (FFSF) paradigm allows to study the mother–infant dyad as a dynamic system coping with social stress perturbations. The State Space Grid (SSG) method is thought to depict both flexibility and stability of the dyad across perturbations, but previous SSG evidence for the FFSF is limited. The main aims were: (1) to investigate mother–infant dyadic flexibility and stability across the FFSF using the SSG; (2) to evaluate the influence of dyadic functioning during Play on infant Still-Face response and of infant stress response in affecting dyadic functioning during Reunion. Forty 4-month-old infants and their mothers were micro-analytically coded during a FFSF and eight SSG dyadic states were obtained. Dyadic flexibility and attractor states were assessed during Play and Reunion. Infants’ stress response was coded as negative engagement during the Still-Face episode. Two dyadic states, “maternal hetero-regulation” and “affective mismatch”, showed significant changes in the number of visits from Play to Reunion. During Play “maternal positive support to infant play” emerged as attractor state, whereas during Reunion a second attractor emerged, namely “affective mismatch”. Dyadic affective mismatch during Play correlated with infants’ negative engagement during Still-Face, whereas infants’ response to Still-Face resulted in minor social matching during Reunion. Findings provide new insights into the flexible, yet stable, functioning of the mother–infant dyad as a dynamic system. Evidence of a reciprocal influence between dyadic functioning and infant social stress response are discussed

Gene function and expression level influence the insertion/fixation dynamics of distinct transposon families in mammalian introns

Background: Transposable elements (TEs) represent more than 45% of the human and mouse genomes. Both parasitic and mutualistic features have been shown to apply to the host-TE relationship but a comprehensive scenario of the forces driving TE fixation within mammalian genes is still missing. Results: We show that intronic multispecies conserved sequences (MCSs) have been affecting TE integration frequency over time. We verify that a selective economizing pressure has been acting on TEs to decrease their frequency in highly expressed genes. After correcting for GC content, MCS density and intron size, we identified TE-enriched and TE-depleted gene categories. In addition to developmental regulators and transcription factors, TE-depleted regions encompass loci that might require subtle regulation of transcript levels or precise activation timing, such as growth factors, cytokines, hormones, and genes involved in the immune response. The latter, despite having reduced frequencies of most TE types, are significantly enriched in mammalian-wide interspersed repeats (MIRs). Analysis of orthologous genes indicated that MIR over-representation also occurs in dog and opossum immune response genes, suggesting, given the partially independent origin of MIR sequences in eutheria and metatheria, the evolutionary conservation of a specific function for MIRs located in these loci. Consistently, the core MIR sequence is over-represented in defense response genes compared to the background intronic frequency. Conclusion: Our data indicate thatgene function, expression level, and sequence conservation influence TE insertion/fixation in mammalian introns. Moreover, we provide the first report showing that a specific TE family is evolutionarily associated with a gene function category

Silencer elements as possible inhibitors of pseudoexon splicing

Human pre-mRNAs contain a definite number of exons and several pseudoexons which are located within intronic regions. We applied a computational approach to address the question of how pseudoexons are neglected in favor of exons and to possibly identify sequence elements preventing pseudoexon splicing. A search for possible splicing silencers was carried out on a pseudoexon selection that resembled exons in terms of splice site strength and exon splicing enhancer (ESE) representation; three motifs were retrieved through hexamer composition comparisons. One of these functions as a powerful silencer in transfection-based splicing assays and matches a previously identified silencer sequence with hnRNP H binding ability. The other two motifs are novel and failed to induce skipping of a constitutive exon, indicating that they might act as weak repressors or in synergy with other unidentified elements. All three motifs are enriched in pseudoexons compared with intronic regions and display higher frequencies in intronless gene-coding sequences compared with exons. We consider that a subpopulation of pseudoexons might rely on negative regulators for splicing repression; this hypothesis, if experimentally verified, might improve our understanding of exonic splicing regulatory sequences and provide the identification of a novel mutation target for human genetic diseases