Stretch activation in muscle: a Ca²⁺ independent mechanism?

The aim of this thesis has been the understanding at the molecular level of stretch activation in muscles. Stretch activation is a feature common to all types of muscle. Such a mechanism is particularly important in cardiac muscles in vertebrates and in indirect flight muscles in insects. Here, the three-dimensional structure of Lethocerus troponin C isoform (F1), recently discovered to be crucial in regulating stretch-activated contraction, is presented. The interactions between F1 and the other subunits of the Lethocerus troponin trimer are also analyzed. Finally a model for stretch activation in muscle, based on the experimental data produced during this thesis, is proposed

Variational approach to gravitational theories with two independent connections

A new variational approach for general relativity and modified theories of gravity is presented. In addition to the metric tensor, two independent affine connections enter the action as dynamical variables. In the matter action the dependence upon one of the connections is left completely unspecified. When the variation is applied to the Einstein-Hilbert action the Einstein field equations are recovered. However when applied to $f(R)$ and Scalar-Tensor theories, it yields gravitational field equations which differ from their equivalents obtained with a metric or Palatini variation and reduce to the former ones only when no connections appear in the matter action.Comment: 11 pages, no figure

Inflationary Perturbations in Palatini Generalised Gravity

We examine the generation of primordial perturbations during an inflationary epoch in generalised theories of gravity when the equations of motion are derived using the Palatini variational principle. Both f(R) and Scalar-Tensor theories are considered and we compare our results with those obtained under the conventional metric formalism. Non-linear generalisations of the action lead to different theories under the two variational choices and we obtain distinct results for scalar and tensor spectral indices and their ratio. We find the following general result; inflation driven solely by f(R) modifications alone do not result in suitable curvature perturbations whilst Scalar-Tensor theories generate nearly scalar invariant curvature perturbations but no tensor modes.Comment: 9 page

Retinoic Acid Specifically Enhances Embryonic Stem Cell Metastate Marked by Zscan4

Pluripotency confers Embryonic Stem Cells (ESCs) the ability to differentiate in ectoderm, endoderm, and mesoderm derivatives, producing the majority of cell types. Although the majority of ESCs divide without losing pluripotency, it has become evident that ESCs culture consists of multiple cell populations with different degrees of potency that are spontaneously induced in regular ESC culture conditions. Zscan4, a key pluripotency factor, marks ESC subpopulation that is referred to as high-level of pluripotency metastate. Here, we report that in ESC cultures treated with retinoic acid (RA), Zscan4 ESCs metastate is strongly enhanced. In particular, we found that induction of Zscan4 metastate is mediated via RA receptors (RAR-alpha, RAR-beta, and RAR-gamma), and it is dependent on phosphoinositide-3-kinase (PI3K) signaling. Remarkably, Zscan4 metastate induced by RA lacks canonical pluripotency genes Oct3/4 and Nanog but retained both self-renewal and pluripotency capabilities. Finally we demonstrated that the conditional ablation of Zscan4 subpopulation is dispensable for both endoderm and mesoderm but is required for ectoderm lineage. In conclusion, our research provides new insights about the role of RA signaling during ESCs high pluripotency metastate fluctuation

Comparative study on the occurrence of polycyclic aromatic hydrocarbons in breast milk and infant formula and risk assessment

The study compared the polycyclic aromatic hydrocarbons (PAH) profile of human milk collected from Italian mothers and different brands of infant formula available on Italian market. Levels of 14 PAHs most frequently occurred in food, PAH markers listed by Commission Regulation (EC) No. 1881/2006, and carcinogenic PAHs classified by the International Agency for Research on Cancer, were determined by high-pressure liquid chromatography with fluorescence detector. The average concentrations of total PAHs were 114.93 in breast milk and 53.68 μg kg-1in infant formula. Furthermore, Benzo(a)pyrene (BaP) and the sum of ∑PAH4 markers (BaP, Chrysene, Benzo(a,h)anthracene and Benzo(b)fluoranthene) were higher than the permissible limit of 1 μg kg-1in 43% and 86% for breast milk and in 10% and 76% for infant formula samples, respectively. Breast milk showed higher levels (P < 0.05) of carcinogenic, and possible carcinogenic hydrocarbons than infant formula samples. Both in human and commercial milk, data showed the occurrence of low and high molecular weight PAHs, respectively from petrogenic and pyrolytic environmental sources, characterizing the infant and mother exposure. Particularly, waste incineration could have represented an important exposure source for infants during breastfeeding, through exposition of mothers resident in some areas of Southern Italy. High PAH levels detected in infant formula enriched with LC-PUFA might be related to the contamination of the vegetable oils added as ingredients. Results showed a high percentage of samples of both breast milk and infant formulas with margin of exposure (MOE) value indicating a potential concern for consumer health

Cesarean scar pregnancy treated by artery embolisation combined with diode laser: a novel approach for a rare disease

Cesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy which represents a consequence of a previous cesarean section. It is associated with major maternal morbidity and mortality and has potential implications on future fertility. Because of possible serious complications, CSP should be swiftly diagnosed and treated. There is no management protocol for this rare, life-threatening condition, and each patient should be evaluated individually. Several types of conservative treatment have been used to treat cesarean scar pregnancy: dilation and curettage (D&C), excision of trophoblastic tissues, local or systemic administration of methotrexate, bilateral hypogastric artery ligation, and selective uterine artery embolization with curettage and/or methotrexate administration. In our study we present a cesarean scar pregnancy of a 40-year-old woman who was treated with angiographic uterine artery embolization (UAE) followed by hysteroscopic diode laser resection. Our combined UAE-hysteroscopic laser surgery appears to offer an effective, safe, and minimally invasive surgical treatment

Voices of the great war: A richly annotated corpus of Italian texts on the first world war

Voci della Grande Guerra (“Voices of the Great War”) is the first large corpus of Italian historical texts dating back to the period ofFirst World War. This corpus differs from other existing resources in several respects. First, from the linguistic point of view it givesaccount of the wide range of varieties in which Italian was articulated in that period, namely from a diastratic (educated vs. uneducatedwriters), diaphasic (low/informal vs. high/formal registers) and diatopic (regional varieties, dialects) points of view. From the historicalperspective, through a collection of texts belonging to different genres it represents different views on the war and the various styles ofnarrating war events and experiences. The final corpus is balanced along various dimensions, corresponding to the textual genre, thelanguage variety used, the author type and the typology of conveyed contents. The corpus is annotated with lemmas, part-of-speech,terminology, and named entities. Significant corpus samples representative of the different “voices” have also been enriched withmeta-linguistic and syntactic information. The layer of syntactic annotation forms the first nucleus of an Italian historical treebankcomplying with the Universal Dependencies standard. The paper illustrates the final resource, the methodology and tools used to buildit, and the Web Interface for navigating it

Characterization of the human STAT5A and STAT5B promoters: evidence of a positive and negative mechanism of transcriptional regulation

AbstractWe recently published the genomic characterization of the STAT5A and STAT5B paralogous genes that are located head to head in the 17q21 chromosome and share large regions of sequence identity. We here demonstrate by transient in vitro transfection that STAT5A and STAT5B promoters are able to direct comparable levels of transcription. The expression of basal promoters is enhanced after Sp1 up-regulation in HeLa and SL2 cells while DNA methylation associated to the recruitment of MeCP2 methyl CpG binding protein down-regulates STAT5A and B promoters by interfering with Sp1-induced transcription. In addition, cross-species sequence comparison identified a bi-directional negative cis-acting regulatory element located in the STAT5 intergenic region