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ENDOTHELIAL-DERIVED Dll4 AND PDGF-BB REPROGRAM COMMITTED SKELETAL MYOBLASTS TO A PERICYTES FATE WITHOUT ERASING THEIR MYOGENIC MEMORY
No full textPericytes are vessel associated mural cells that form the smooth muscle layer of vessels. They are able to contribute to skeletal muscle regeneration as previously demonstrated for mesoangioblasts that indeed represent their in vitro counterpart. Pericytes are a heterogeneous population characterized by different marker like Alkaline Phosphatase, Smooth muscle actin, Neuro glial2 (NG2). Endothelial cells recruit pericytes from the surrounding mesoderm progenitor through a PDGF-PDGFrB loop.
In this work I have conducted experiments whose results showed that functional pericytes may derive from direct reprogramming of already committed embryonic and, less frequently, fetal skeletal myoblasts. When co-transplanted in vivo with endothelial cells, Pax3 or Myf5 expressing myoblasts, downregulate myogenic genes, with the notable exception of Myf5, upregulate pericyte markers, adopting a perithelial position and morphology in newly formed vessel networks. The activity of endothelial cells can be replaced by exposure to PDGF-BB and Dll4 but not Dll1 or Jagged 1, while inhibition of Notch signaling via a γ-secretase inhibitor completely restores myogenesis, confirming that the skeletal myogenic program is not irreversibly erased.
Notch activation in MyoD expressing embryonic cells in vivo abolishes myogenesis but not Myf5 expression that however cannot activate myogenin
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and trigger myogenesis because Notch, beside suppressing MyoD transcription, activates Id and Twist factors that bind to and inhibit Myf5 transcriptional activity. Myf5 expressing cells activate pericyte genes and adopt a perithelial position, a phenomenon that can be rarely observed also in WT embryos.
These data demonstrate that endothelial cells are able to directly reprogram committed skeletal myoblasts to mature pericytes for the formation and stabilization of vessel wall, suggesting that reprogramming occurs as a natural developmental process that leads in a sort of competition between endothelium and muscle.European Community (OptiStem and Angioscaff), Association Française contre les Myopathies (AFM) CureDuchenne and the Italian Ministries of Research (FIRB) and Health
Corrosion behavior of bronze alloys exposed to urban and marine environment: an innovative approach to corrosion process understanding and to graphical results presentation
No full textDelving into the complexity of consumer green purchasing behaviour. A multiple method approach
No full textLa guerra russo-giapponese (1904-1905) attraverso le testimonianze dei corrispondenti della stampa e degli addetti militari italiani
No full textThe work focuses on the Russo-Japanese war, and intends to attempt to achieve a
synthesis between the technical military aspects and those concerning with the political,
economic, administrative and social reality-in the period between the late ‘800 and early
new century-of Russia and Japan as those directly involved in the conflict, and China,
as holder of the territorial and colonial interests of contention. This study is, therefore,
an attempt at innovation, as it wants to propose an organic reading of two integrated and
inextricably linked realities yet treated, almost always, separately.
Overall, the examination of archival documents and literature (also derived from other
scientific fields than military historiography, such as the history of photography, of
narrative, or of mass communication) has confirmed the initial assumptions. The
admission into the search for “enrichments” relating to different conflicts and
disciplinary areas, has been the subject of long consideration, not wanting to slip into
digressions that lead the development of the work away from the initial intent. It is
therefore conducted in a supervised way, strictly maintained in the channel of the topic
and, ultimately, subordinate to purposes of functionality.
In the selection and analysis of primary sources, the report on the Anglo Boer War of
Major Domenico Gentilini has proved to be of particular interest. It was therefore
decided to place it in cross-sectional connection with the almost contemporary Russo-
Japanese war. Despite the profound differences of structure, of context, techniques and
of conduct of military operations, the substantial comparative insights help to highlight
peculiar aspects and critical issues of the conflict protagonist of this study.
With regard, however, sources and literature “borrowed” from the history of
photography, from narrative and from social sciences, they complete the reference
framework of research and, in some cases, provide data to submit to analysis (think of
the visual and literary materials, both for official propaganda, and for personal use,
related to the Russo-Japanese War).
The general structure imposed to the work, is structured into four chapters. The first,
after an introductory part, addresses the historical and political background of the
conflict. In the first three paragraphs (on China, on Russia and on Japan) we set out to
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outline the historical, political, economic and social situation of the countries under
review, in order to provide the necessary elements to understand the causes that led to
conflict. These last are examined in more detail in the fourth paragraph. The technical
military aspects are developed in the fifth, sixth and seventh paragraph, which
examines: the location, the number and types of forces in the field; the weapons, the
strategies and the tactics used during the conflict; the strategic planning on conduct of
the military operations by the General Staffs of the belligerent powers. The eighth
paragraph, finally, is dedicated to a brief excursus at the visual and literary materials
used for propaganda purposes. I considered that, in examining all aspects of the conflict,
it was necessary one, although brief, verification on what I have called the war of
images, since representations of other nations produced by a Country are largely
instrumental in mobilizing the public opinion, and take on such importance that cannot
be neglected in considering the system of the balances of international relations.
The second chapter focuses exclusively on military operations, both ground and
maritime. According to the chronological order of the conflict. In the first analysis the
ground one, to pass then to the maritime one through the major battles that have
characterized it and with particular attention to the strategic and tactical aspects and to
the use of new technologies of war.
The third chapter examines the activities of the Italian press officer (Luigi Barzini), the
Italian military officers (Filippo Camperio and Enrico Caviglia), and the military
officer at the Italian Embassy at St. Petersburg (Paolo Ruggeri Laderchi), in order to
better understand the important political implications, through the War reports, the
memoranda, or the military-diplomatic correspondence with the Italian General Staff.
Those documents have been reported, selected in their most intense and significant
parts, compared and discussed.
The fourth chapter contains the conclusions
Complexity in Financial Markets: Modeling Psychological Behavior in Agent-Based Models and Order Book Models
No full textThe fundamental idea developed throughout this work is the introduction of new
metrics in Social Sciences (Economics, Finance, opinion dynamics, etc). The concept
of metric, that is the concept of measure, is usually neglected by mainstream
theories of Economics and Finance. Financial Markets are the natural starting
point of such an approach to Social Sciences because a systematic approach can
be undertaken and the methods of Physics has shown to be very effective. In fact
since a decade there exists a very huge amount of high frequency data from stock
exchanges which permit to perform experimental procedures as in Natural Sciences.
Financial markets appear as a perfect playground where models can be tested and
where repeatability of empirical evidences are well-established features differently
from, for instance, Macro-Economy and Micro-Economy. Thus Finance has been
the first point of contact for the interdisciplinary application of methods and tools
deriving from Physics and it has been also the starting point of this work.
We investigated the origin of the so-called Stylized Facts of financial markets (i.e.
the statistical properties of financial time series) in the framework of agent-based
models. We found that Stylized Facts can be interpreted as a finite size effect in
terms of the number of effectively independent agents (i.e. strategy) which results
to be a key variable to understand the self-organization of financial markets.
As a second issue we focused our attention on the order book dynamics both
from a theoretical and a data oriented point of view. We developed a zero intelligence
model in order to investigate the role of vanishing liquidity in the price
response to incoming orders. Within the framework of this model we have analyzed
the effect of the introduction of strategies pointing out that simple strategic
behaviors can explain bursts of intermittency and long memory effects. On the
other hand we quantitatively showed that there exists a feedback effect in markets
called self-fulfilling prophecy which is the mechanism through which technical trading
can exist and work. This feature is a very interesting quantitative evidence
of a self-reinforcement of agents’ belief. Last but not least nowadays we live in
a computerized and networked society where many of our actions leave a digital
trace and affect other people’s actions. This has lead to the emergence of a new
data-driven research field. In this work we highlighted how non financial data can
be used to track financial activity, in detail we investigate query log volumes, i.e.
the volumes of searches for a specific query done by users in a search engine, as a
proxy for trading volumes and we find that users’ activity on Yahoo! search engine
anticipates trading volume by one-two days.
Differently from Finance, Economics is far from being an ideal candidate to
export the methodology of Natural Sciences because of the lack of empirical data
since controlled (and repeatable) experiments are totally artificial while real experiments
are almost incontrollable and non repeatable due to a high degree of non
stationarity of economical systems. However, the application of method deriving
from complexity to the Economics of Growth is one of the more important achievement
of the work here developed. The basic idea is to study the network defined
by international trade flows and introduce a (non-monetary) metric to measure the
complexity and the competitiveness of countries’ productive system. In addition
we are able to define a metric for products’ quality which overcomes traditional
economic measure for the quality of products given in terms of hours of qualified
labour needed to produce a good. The method developed provides some impressive
results in predicting economical growth of countries and offers many opportunities
of improvements and generalizations
Optical studies of micron-scale flows: holographic microscopy, optical trapping and superhydrophobicity
No full textMicrofluidics is a very recent branch of science and technology. The
development and the success, it has had in the last 15 years, is mainly due to
the concept of lab-on-a-chip. Those miniaturized devices, integrating one or
more laboratory functions, have aroused great interest among several research
areas as physics, chemistry, biology and bioengineering. When a fluid is
confined in a micro or nano scale structure, its behaviour is strongly affected
by its interactions with the surrounding surfaces. In this context, the theme
of fluid/solid slippage has been widely studied both theoretically and
experimentally. Innovative technologies to enhance the surface slippage by
specifically designing the solid interfaces have reportedly demonstrated to be an
effective way to reduce the fluid/solid friction. To this end,
superhydrophobic surfaces have increasingly attracted the interest of the
scientific and technological community thanks to the large wall-slippage they
present for liquid water. Though their behaviour has been extensively
investigated through several theoretical and numerical methods, the experimental
approaches are still indispensable to test and understand the properties of
these surfaces. However, the lack of a general predicting model is also due to
the fact that no one of the several existing experimental techniques has shown
up as a very reliable one. Indeed, the reported measurements of slippage still
depends on the specific adopted method, thwarting attempts to corroborate the
proposed theoretical and numerical schemes. Therefore, it is evident that a
more sensitive and effective experimental technique is still missing.
This thesis began and developed inside the wider project of setting up an innovative
technique to investigate the fluid-solid slippage on superhydrophobic surfaces by means of optical
tweezers. Even though this project is still going on, this work reports the steps performed
along the long way towards this main goal and it consists of a collection
of several researches involving different scientific fields as optics,
microscopy, surface science, microhydrodynamics, microfluidics and
microfabrication.
The researches presented in this work can be separated in two main categories:
i) holographic micromanipulation and microscopy, ii) superhydrophobicity.
Accordingly, the thesis is divided in two Parts. In the first Part, holography
is adopted to accomplish two completely different tasks. Projecting an
hologram on a spatial light modulator, the light intensity of a coherent source
is modified at will so that several optical traps are generated in the sample
volume. In this scheme, the laser light is an input of the microscope system
and it used as an active tool to manipulate micron-scale objects and investigate
the surrounding fluid. On the other hand, illuminating the sample through a
monochromatic plane wave generates an hologram, recorded on CMOS camera, that
contains the information of the light intensity distribution in the entire
sample volume. In this case, the coherent light is the output of the microscope
system and provides a tool for three-dimensional visualization and analysis of
the examined sample. In such a context, if we regard a trapped bead as a local
probe of fluid properties, holographic optical trapping allows us to trap
multiple particles at the same time and to freely move them throughout the
sample volume.
The second Part of the thesis deals with the experimental characterization of the superhydrophobicity
and slippage properties of silicon surfaces.
Micro particle image velocimetry is adopted to provide a reference standard
characterization of microgrooved silicon superhydrophobic samples that would be
very useful in view of a validation of holographic trapping measurements of
fluid/solid slippage. However, what was initially conceived as a standard
approach has revealed some interesting aspects that have been deeply
investigated, as the role of the curvature and position of the liquid/air meniscus inside the
microgrooves and the detrimental effect of the contamination of the liquid/air interface.
As regards microfabrication,
we also discuss an easy-to-implement and very cheap procedure to turn a silicon flat sample
into a superhydrophobic surface
via porosification.
Demonstrating the capabilities of digital holographic microscopy and
holographic tweezers to locally probe the fluid properties in terms of high
accuracy measurements and high spatial resolution, the work presented in this
thesis paves the way for superhydrophobicity characterization via holographic
tweezers and digital holographic microscopy.The thesis developed within the framework of an international joint Ph.D. studentiship between University of Rome La Sapienza and University of Lyon, University Claude Bernard Lyon 1.2009 Da Vinci Research Grant, Università Franco-Italiana / 4-month Research Grant, French Embassy in Ital
Thyroid hormone and diabetes:an anti-apoptotic pro-survival opportunity for pancreatic b cells.
No full textPancreatic β cell loss is the key factor in the pathogenesis of both type 1 and type 2 diabetes, being mainly due to apoptosis of the β cell. Therefore, it is conceivable that a valuable approach to treat or even to prevent the onset of diabetes may imply an anti-apoptotic pro-survival therapy of β cell.
Ex vivo islet cell culture in the presence of stimulating factors prior to transplantation is considered a good strategy in contrast to the short conclusion of islets transplantation. Previously, I demonstrated how T3 can increase β cell function via specific activation of Akt; therefore I, firstly, hypothesized that thyroid hormone T3 can be considered a promising candidate for the in vitro expansion of islet cell mass. Rat pancreatic islets have been isolated by collagenase digestion and cultured in the presence or not of T3 10⁻⁷ M. Islets viability has been evaluated by two different dyes, one cell-permeable green fluorescent and propidium iodide, and by the analysis of core cell damage upcoming. Moreover, islets function has been evaluated by insulin secretion. The ability of β cells to counteract apoptosis induced by streptozotocin has been analyzed by TUNEL assay. In addition, core cell damage was sensibly reduced by T3, suggesting the preservation of the β cells integrity during the culture period. I demonstrated that treatment of primary cultures of rat pancreatic islets with T3 results in augmented β-cell vitality and function. Since even insulin secretion was sensibly augmented by T3 stimulation. Moreover the strong increment shown in Akt activation suggests the involvement of this pathway in the observed phenomena. This study indicate T3 as a good factor to improve ex vivo islets cell culture.
In the second part of my study I demonstrated that the thyroid hormone T3 counteracts the onset of a Streptozotocin (STZ) induced diabetes in wild type mice. To test my hypothesis diabetes has been induced in Balb/c male mice by multiple low dose Streptozotocin injection and a group of mice was contemporaneously injected with T3. After 48 h mice were tested for glucose tolerance test, insulin serum levels and then sacrificed. Whole pancreata were utilized for morphological and biochemical analyses, while protein extracts and RNA were utilized for expression analyses of specific molecules. The results showed that islets from T3 treated mice were comparable to age- and sex-matched control, untreated mice in number, shape, dimension, consistency, ultrastructure, insulin and glucagon levels, TUNEL positivity and caspases activation, while all the cited parameters and molecules were altered by STZ alone. The T3-induced pro survival effect was associated with a strong increase in phosphorylated Akt. Moreover, T3 administration prevented the STZ-dependent alterations in glucose blood level, both during fasting and after glucose challenge, as well as in insulin serum level. In conclusion I demonstrated that T3 could act as a protective factor against STZ induced diabetes
