Mammalian telomeres and their partnership with lamins

Chromosome ends are complex structures, which require a panel of factors for their elongation, replication, and protection. We describe here the mechanics of mammalian telomeres, dynamics and maintainance in relation to lamins. Multiple biochemical connections, including association of telomeres to the nuclear envelope and matrix, of telomeric proteins to lamins, and of lamin-associated proteins to chromosome ends, underline the interplay between lamins and telomeres. Paths toward senescence, such as defective telomere replication, altered heterochromatin organization, and impaired DNA repair, are common to lamins' and telomeres' dysfunction. The convergence of phenotypes can be interpreted through a model of dynamic, lamin-controlled functional platforms dedicated to the function of telomeres as fragile sites. The features of telomeropathies and laminopathies, and of animal models underline further overlapping aspects, including the alteration of stem cell compartments. We expect that future studies of basic biology and on aging will benefit from the analysis of this telomere-lamina interplay

CAV-2 Vector Development and Gene Transfer in the Central and Peripheral Nervous Systems

The options available for genetic modification of cells of the central nervous system (CNS) have greatly increased in the last decade. The current panoply of viral and nonviral vectors provides multifunctional platforms to deliver expression cassettes to many structures and nuclei. These cassettes can replace defective genes, modify a given pathway perturbed by diseases, or express proteins that can be selectively activated by drugs or light to extinguish or excite neurons. This review focuses on the use of canine adenovirus type 2 (CAV-2) vectors for gene transfer to neurons in the brain, spinal cord, and peripheral nervous system. We discuss (1) recent advances in vector production, (2) why CAV-2 vectors preferentially transduce neurons, (3) the mechanism underlying their widespread distribution via retrograde axonal transport, (4) how CAV-2 vectors have been used to address structure/function, and (5) their therapeutic applications

Bend sensor arrays for hand movement tracking in biomedical systems

Bend sensor’s electrical feature and mechanical pliability allow to easily realize a cost effective and reliable system to measure human postures. With this kind of sensors we realized a data glove capable to accurately measure all degree of freedom of a human hand. In particular, in collaboration with the Flexpoint Sensor Systems Inc., we designed and realized a unique device capable to measure at the same time the flex-extension movements of the three joints of one finger. Experimental results demonstrated good performances obtained in terms of accuracy and repeatability of the measures

Fast-slow bursters in the unfolding of a high codimension singularity and the ultra-slow transitions of classes

Bursting is a phenomenon found in a variety of physical and biological systems. For example, in neuroscience, bursting is believed to play a key role in the way information is transferred in the nervous system. In this work, we propose a model that, appropriately tuned, can display several types of bursting behaviors. The model contains two subsystems acting at different timescales. For the fast subsystem we use the planar unfolding of a high codimension singularity. In its bifurcation diagram, we locate paths that underly the right sequence of bifurcations necessary for bursting. The slow subsystem steers the fast one back and forth along these paths leading to bursting behavior. The model is able to produce almost all the classes of bursting predicted for systems with a planar fast subsystems. Transitions between classes can be obtained through an ultra-slow modulation of the model's parameters. A detailed exploration of the parameter space allows predicting possible transitions. This provides a single framework to understand the coexistence of diverse bursting patterns in physical and biological systems or in models.Comment: 22 pages, 15 figure

Methods and hints to linearise the resistance values vs. bending angle relationship of bend sensors

The correct measure of static and dynamic postures of patients is a fundamental element for dispensing correct rehabilitation procedures. Nowadays there are different sensors and transducers useful to reach the aim of measuring human postures, even in a non uncomfortable way, during normal activities of everyday life. Among all these sensors we selected the flex ones stand their cheapness an good performances in terms of reliability and stability of electrical signal they provide. It is possible to measure flex-extension of human joints simply laying the flex sensors on wrist, knee, elbow, ankle, etc. But a drawback is paid for these sensors, because of a non linear function of their electrical resistance variation vs. bending angle. The non linearity involves a time consuming calibration, more complexity of the conditioning electronics, more troubles for drift problems and the issue to establish the best fit algorithm. So here we propose methodologies and hints to linearise the sensor’s electrical function

Electrical Resistance Profiling of Bend Sensors adopted to Measure Spatial Arrangment of the Human Body

We report some techniques we adopted to electrically characterize some commercially available bend sensors, in terms of their resistance variations when curved or angular shaped. This study has the aim of a correct exploitation of the bend sensors in order to adopt them for proper measures of the static postures and kinematics of the total human body, in regards for both the trunk and the limb

Genomic instability and DNA replication defects in progeroid syndromes

Progeroid syndromes induced by mutations in lamin A or in its interactors – named progeroid laminopathies – are model systems for the dissection of the molecular pathways causing physio- logical and premature aging. A large amount of data, based mainly on the Hutchinson Gilford Progeria syndrome (HGPS), one of the best characterized progeroid laminopathy, has highlighted the role of lamins in multiple DNA activities, including replication, repair, chromatin organization and telomere function. On the other hand, the phenotypes generated by mutations affecting genes directly acting on DNA function, as mutations in the helicases WRN and BLM or in the polymerase polδ, share many of the traits of progeroid laminopathies. These evidences support the hypothesis of a concerted implication of DNA function and lamins in aging. We focus here on these aspects to contribute to the comprehension of the driving forces acting in progeroid syndromes and premature aging

The Effects of Partial Employment Protection Reforms: Evidence from Italy (joint with Sabrina Di Addario and Diego Daruich)

Concerns over labor market flexibility have been at the center of the European political debate for the past three decades. In response to the widespread belief that rigid employment protection laws (EPL) depress employment, many countries including France, Spain, and Italy undertook reforms that substantially relaxed legal constraints on the use of temporary employment contracts. Importantly, however, these reforms were often only partial in that the degree of employment protection granted to workers hired via permanent employment contracts remained unchanged, leading to a fundamentally dual labor market. This dissertation examines detailed Italian social security records matched with firm financial data and a difference-in-differences research design to provide a comprehensive empirical evaluation of an Italian partial reform signed into law in 2001 which help illuminate how the reform affected overall employment and labor income, what factors contributed to success or failure in raising wages and employment, and were there heterogenous effects across different worker and firm groups