Craniofacial growth and development in modern humans and Neanderthals

This thesis assesses craniofacial growth, development and the dynamics of developmental interactions among cranial regions in modern humans and Neanderthals. To these ends, virtual segmentation, landmarking and Geometric Morphometrics (GM) are applied to an ontogenetic series of the whole crania of 68 H. sapiens and 12 H. neanderthalensis. First, the ontogenetic shape and form changes in the cranial vault, base and face are explored, and the locations and magnitudes of these changes are discussed. Secondly, allometric scaling is tested for differences among different age classes in the three regions of the cranium. In addition, the degree of covariation among these and how it changes over time is investigated.The study then focuses on interactions among facial regions. First, similar analyses as those used in the study of the cranium are applied to compare growth, development and covariation among parts of the face in different age classes. Additionally, a sample of 227 modern humans from 0 to 6 years of age is analysed using path analysis, to investigate the cascade of interactions and relative contributions of soft tissue and skeletal elements to the overall growth and development of the face. Last, the facial morphology of H. sapiens is compared to that of H. neanderthalensis and their ontogenetic trajectories are tested for divergence. Novel method registration-free colour maps are used to visualise regional changes during growth and development and to compare the morphologies of the two species. Covariation among facial elements is also compared to assess potential differences in developmental interactions. In modern humans, the results show that allometry and covariation change significantly among age classes and between cranial regions during ontogeny and that covariation is stronger in younger subadults than in older subadults and adults. Among modern humans, significantly divergent trajectories are observed between age classes during ontogeny in all three cranial regions. In the modern human face, allometric scaling also differs among age stages in each region. Interestingly, covariation among facial regions becomes progressively non-significant with time, with the exception of those including the nose and maxilla. Path analysis in modern humans shows a large contribution of the proxy used for nasal septum to the overall facial development. Soft tissues contribute only locally to the development of some skeletal elements of the face. Major aspects of the differences between adult modern humans and Neanderthals are already present in the youngest individuals. However, additional differences arise through differences in the degree of change in facial size and significantly divergent allometric trajectories. Analyses of covariation among Neanderthal facial regions suffer from small sample size but, where significant, suggest that the interactions among cranial components are similar to those in modern humans, with some differences

The genetic susceptibility in the development of malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a cancer of the pleural cavity whose main risk factor is exposure to asbestos. However, it has been shown that only a minority of exposed people develops MPM. In fact, the incidence among professionally exposed workers was shown to vary between 0.5% and 18.0%. Various hints suggested that other important cofactors could play a role, in particular the genetic susceptibility. Impressive is the case of Cappadocians families exposed to erionite and affected by an "epidemic" of MPM with about half of the inhabitants dying for the disease. However, no results for a "Cappadocia" gene of susceptibility to MPM have been obtained yet and more studies are needed. Among asbestos-exposed workers, several studies reported familial cases of MPM, suggesting that heredity could be important in the tumor development. However, large studies on familial clusters showed only weak increased risks that could be attributable also to indirect exposures in a contaminated household. Moreover, the risk of developing MPM is increased of a limited extent among people exposed to asbestos with a positive history of familial cancers. A particular is represented by carriers of germline mutations within BAP1 gene. In families and in animal models, mutations within BAP1 are strongly predisposing to develop MPM. However, also other types of cancer (such as uveal melanoma) are present, thus BAP1 mutations are considered as responsible for a hereditary form of a multi-cancer syndrome. In any case, among sporadic MPM, the prevalence of germline BAP1 mutations is negligible. Finally, genetic studies highlighted the presence of low-risk susceptibility alleles, such as those within XRCC3, NAT2 or GSTM1. Two different genome-wide association studies could not find positive associations reaching the genome-wide statistical significance threshold, however, both were concordant in showing a weak signal within the SDK1 gene region. Overall, it could be concluded that, as for other types of sporadic cancers, the susceptibility to develop MPM following asbestos exposure is modulated moderately by the individual genetic background. Further studies on larger series could help in a better characterization of more genes predisposing to MPM, being this tumor a rare disease

More targets, more pathways and more clues for mutant p53.

Mutations in the transcription factor p53 are among the most common genetic alterations in human cancer, and missense p53 mutations in cancer cells can lead to aggressive phenotypes. So far, only few studies investigated transcriptional reprogramming under mutant p53 expression as a means to identify deregulated targets and pathways. A review of the literature was carried out focusing on mutant p53-dependent transcriptome changes with the aims of (i) verifying whether different p53 mutations can be equivalent for their effects, or whether there is a mutation-specific transcriptional reprogramming of target genes, (ii) understanding what is the main mechanism at the basis of upregulation or downregulation of gene expression under the p53 mutant background, (iii) identifying novel candidate target genes of WT and/or mutant p53 and (iv) defining cellular pathways affected by the mutant p53-dependent gene expression reprogramming. Nearly 600 genes were consistently found upregulated or downregulated upon ectopic expression of mutant p53, regardless of the specific p53 mutation studied. Promoter analysis and the use of ChIP-seq data indicate that, for most genes, the expression changes could be ascribed to a loss both of WT p53 transcriptional activation and repressor functions. Pathway analysis indicated changes in the metabolism/catabolism of amino acids such as aspartate, glutamate, arginine and proline. Novel p53 candidate target genes were also identified, including ARID3B, ARNT2, CLMN, FADS1, FTH1, KPNA2, LPHN2, PARD6B, PDE4C, PIAS2, PRPF40A, PYGL and RHOBTB2, involved in the metabolism, xenobiotic responses and cell differentiation

A passivity-based strategy for manual corrections in human-robot coaching

In recent years, new programming techniques have been developed in the human-robot collaboration (HRC) field. For example, walk-through programming allows to program the robot in an easy and intuitive way. In this context, a modification of a portion of the trajectory usually requires the teaching of the path from the beginning. In this paper we propose a passivity-based method to locally change a trajectory based on a manual human correction. At the beginning the robot follows the nominal trajectory, encoded through the Dynamical Movement Primitives, by setting high control gains. When the human grasps the end-effector, the robot is made compliant and he/she can drive it along the correction. The correction is optimally joined to the nominal trajectory, resuming the path tracking. In order to avoid unstable behaviors, the variation of the control gains is performed exploiting energy tanks, preserving the passivity of the interaction. Finally, the correction is spatially fixed so that a variation in the boundary conditions (e.g., the initial/final points) does not affect the modification

The Effect of Age and NT-proBNP on the Association of Central Obesity with 6-Years Cardiovascular Mortality of Middle-Aged and Elderly Diabetic People: The Population-Based Casale Monferrato Study

BACKGROUND: Among people with type 2 diabetes the relationship between central obesity and cardiovascular mortality has not been definitely assessed. Moreover, NT-proBNP is negatively associated with central obesity, but no study has examined their combined effect on survival. We have examined these issues in a well-characterized population-based cohort. METHODS AND FINDINGS: Survival data of 2272 diabetic people recruited in 2000 who had no other chronic disease have been updated to 31 December 2006. NT-proBNP was measured in a subgroup of 1690 patients. Cox proportional hazards modeling was employed to estimate the independent associations between cardiovascular and all-cause mortality and waist circumference. Mean age was 67.9 years, 49.3% were men. Both age and NT-proBNP were negatively correlated with waist circumference (r = -0.11, p<0.001 and r = -0.07, p = 0.002). Out of 2272 subjects, 520 deaths (221 for CV mortality) occurred during a median follow-up of 5.4 years. Central obesity was not associated with CV mortality (hazard ratio, HR, adjusted for age, sex, diabetes duration, 1.14, 95% CI 0.86-1.52). NTproBNP was a negative confounder and age a strong modifier of this relationship (p for interaction<0.001): age<70 years, fully adjusted model HR = 3.52 (1.17-10.57) and age ≥70 years, HR = 0.80 (0.46-1.40). Respective HRs for all-cause mortality were 1.86 (1.03-3.32) and 0.73 (0.51-1.04). CONCLUSIONS: In diabetic people aged 70 years and lower, central obesity was independently associated with increased cardiovascular mortality, independently of the negative effect of NT-proBNP. In contrast, no effect on 6-years survival was evident in diabetic people who have yet survived up to 70 years

walk through programming for industrial applications

Abstract Collaboration between humans and robots is increasingly desired in several application domains, including the manufacturing domain. The paper describes a software control architecture for industrial robotic applications allowing human-robot cooperation during the programming phase of a robotic task. The control architecture is based on admittance control and tool dynamics compensation for implementing walk-through programming and manual guidance. Further steps to integrate this system on a real set-up include the robot kinematics and a socket communication that sends a binary file to the robot

Homo sapiens natriuretic peptide precursor type C (NPPC) mRNA,partial cds and 3\u27 UTR.

LOCUS HQ419060 318 bp mRNA linear PRI 24-NOV-2010 DEFINITION Homo sapiens natriuretic peptide precursor type C (NPPC) mRNA, partial cds and 3\u27 UTR. ACCESSION HQ419060 VERSION HQ419060.1 GI:312261407 KEYWORDS . SOURCE Homo sapiens (human) ORGANISM Homo sapiens Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. REFERENCE 1 (bases 1 to 318) AUTHORS Landi,S., Melaiu,O., Cabiati,M., Landi,D., Caselli,C., Prescimone,T., Giannessi,D., Gemignani,F. and Del Ry,S. TITLE Direct Submission JOURNAL Submitted (20-OCT-2010) Laboratory of Cardiovascular Biochemistry, Institute of Clinical Physiology, Via Moruzzi 1, Pisa, PI 56100, Italy FEATURES Location/Qualifiers source 1..318 /organism="Homo sapiens" /mol_type="mRNA" /db_xref="taxon:9606" /cell_line="SKNBE" /PCR_primers="fwd_seq: gtcagaagaagggcgacaag, rev_seq: gcgtttaaacgcgcacgcgt" gene <1..318 /gene="NPPC" CDS <1..188 /gene="NPPC" /codon_start=3 /product="natriuretic peptide precursor type C" /protein_id="ADQ54381.1" /db_xref="GI:312261408" /translation="GDRSRLLRDLRVDTKSRAAWARLLQEHPNARKYKGANKKGLSKG CFGLKLDRIGSMSGLGC" 3\u27UTR 189..318 /gene="NPPC" ORIGIN 1 agggcgaccg gtcgcgactg ctccgggacc tgcgcgtgga caccaagtcg cgggcagcgt 61 gggctcgcct tctgcaagag caccccaacg cgcgcaaata caaaggagcc aacaagaagg 121 gcttgtccaa gggctgcttc ggcctcaagc tggaccgaat cggctccatg agcggcctgg 181 gatgttagtg cggcgccccc tggcggcggg agaagaatga ttctgacact tggggaccag 241 ccttcagtag ctacccttgg aatgcctttg ctctcttctc tcctgtctaa acaacaaaga 301 gacggagtct gaggcct

Sixteenth-Century Italian Literature and Author Philology: Three Examples (Marino, Stigliani, Tesauro)

Para el siglo XVII la filología de autor registra, con escasas excepciones, una penuria tanto de ediciones modernas y críticas como de estudios filológicos. Los tres casos que se estudian aquí, aunque muy diferentes entre sí, muestran cómo la investigación en este campo permite reunir valiosa información sobre la forma de trabajar de los autores del Barroco. Por lo que atañe a Marino, se revisa la situación de las Rime, la Galeria y el Adoney se brinda una primera valoración de las circunstancias y de los problemas de la tradición textual, a partir de los varios tipos de documentos supérstites (originales y ediciones al cuidado del autor). En cuanto a Stigliani, se ofrece una visión general de la gran variedad de materiales hoy disponibles: impresos, manuscritos y apostillas, que atestiguan un incansable proceso de reelaboración, en el cual influyeron de forma acusada las vicisitudes personales del propio escritor. El caso de Tesauro, final-mente, se presenta a través de su obra más conocida, Il Cannocchiale aristotelico, para la cual el cotejo de las ediciones significativas ha puesto de relieve las variaciones tanto en la estructura general del libro como en porciones aisladas del texto.In the field of the authorial philology, with very few exceptions, for the 17th century there is a dramatic lack of both modern and critical editions and, consequently, of philological studies. The three cases presented here, although very different from each other, show how research in this field allows us to gather valuable information on the way seventeenth-century authors worked. For Marino, by reviewing the cases of Rime, Galeria and Adone, an initial assessment of the aspects and problems of the tradition of Marino’s texts has been attempted, starting with the typology of the surviving elaborative materials. In the case of Stigliani, a general overview is offered of the great mass of material available, consisting of prints, manuscripts and marginalia, witnesses to a tireless process of re-elaboration that was largely influenced by the author’s personal vicissitudes. The case of Tesauro is instead presented through his best-known work, Il Cannocchiale Aristotelico, for which a comparison of the most significant editions has highlighted the variations in both the general structure of the book and the individual textual portions

Identification of MiR-21-5p as a functional regulator of mesothelin expression using microRNA capture affinity coupled with next generation sequencing

MicroRNAs (miRNAs) are small non-coding RNAs that regulate mRNA expression mainly by silencing target transcripts via binding to miRNA recognition elements (MREs) in the 3′untranslated region (3′UTR). The identification of bona fide targets is challenging for researchers working on the functional aspect of miRNAs. Recently, we developed a method (miR-CATCH) based on biotinylated DNA antisense oligonucleotides that capture the mRNA of interest and facilitates the characterisation of miRNAs::mRNA interactions in a physiological cellular context. Here, the miR-CATCH technique was applied to the mesothelin (MSLN) gene and coupled with next generation sequencing (NGS), to identify miRNAs that regulate MSLN mRNA and that may be responsible for its increased protein levels found in malignant pleural mesothelioma (MPM). Biotinylated MSLN oligos were employed to isolate miRNA::MSLN mRNA complexes from a normal cell line (Met-5A) which expresses low levels of MSLN. MiRNAs targeting the MSLN mRNA were identified by NGS and miR-21-5p and miR-100-5p were selected for further validation analyses. MiR-21-5p was shown to be able to modulate MSLN expression in miRNA mimic experiments in a panel of malignant and non-malignant cell lines. Further miRNA inhibitor experiments and luciferase assays in Mero-14 cells validated miR-21-5p as a true regulator of MSLN. Moreover, in vitro experiments showed that treatment with miR-21-5p mimic reduced proliferation of MPM cell lines. Altogether, this work shows that the miR-CATCH technique, coupled with NGS and in vitro validation, represents a reliable method to identify native miRNA::mRNA interactions. MiR-21-5p is suggested as novel regulator of MSLN with a possible functional role in cellular growth