Apoptotic pathways in the pathogenesis of pemphigus: targets for new therapies

Pemphigus is a group of rare autoimmune blistering diseases of the skin in which autoantibodies to desmosome cadherins, desmogleins, induce loss of cell-cell adhesion (acantholysis). In addition to steric hindrance and activation of intracellular phosphorylation cascade signaling pathways, apoptosis has been suggested to contribute to the mechanism by which pathogenic IgG induces acantholysis. We review the literature examining the role of apoptosis in pemphigus. Current data recognize a central role of apoptosis in the mechanisms of blister induction. In particular, here we stress the key role of FasL in pemphigus, as it is able to first induce apoptosis, then acantholysis. Being pro-apoptotic molecules important in blister formation, they could represent new specific targets for pemphigus treatment

Survivin: a dual player in healthy and diseased skin

Survivin belongs to the inhibitor of apoptosis (IAP) protein family, and, in addition to the antiapoptotic functions, it also regulates the cell cycle. The survivin gene generates five major isoforms with diverse and opposite functions. Survivin is highly expressed in cancer and in few normal adult tissues, including skin. It is mostly detected in the nucleus of keratinocyte stem cells (KSCs), but it is also expressed in melanocytes and fibroblasts. Survivin isoforms are differentially detected in subpopulations of human keratinocytes, exerting contrasting activities. Survivin has an important role in the regulation of cell cycle in keratinocytes, and it protects these cells from anoikis and UV-induced apoptosis. In melanoma, survivin is abundantly expressed, and its subcellular localization varies depending upon tumor thickness and invasiveness. Survivin overexpression has been shown in squamous cell carcinoma (SCC), and it is also involved in UVB-induced carcinogenesis. The presence of survivin both in the nucleus and in the cytoplasm throughout the epidermal layers of psoriatic lesions suggests the involvement of this protein in the keratinocyte alterations typical of this disease. Additional studies on the expression of survivin isoforms and their subcellular localization in relation to function will confirm the key role of survivin in the skin and will open the field to new therapeutic strategies for many cutaneous condition

Entangled symmetric states and copositive matrices

Entanglement in symmetric quantum states and the theory of copositive matrices are intimately related concepts. For the simplest symmetric states, i.e., the diagonal symmetric (DS) states, it has been shown that there exists a correspondence between exceptional (non-exceptional) copositive matrices and non-decomposable (decomposable) Entanglement Witnesses (EWs). Here we show that EWs of symmetric, but not DS, states can also be constructed from extended copositive matrices, providing new examples of bound entangled symmetric states, together with their corresponding EWs, in arbitrary odd dimensions

CD271 downregulation promotes melanoma progression and invasion in 3-dimensional models and in zebrafish

CD271 is a neurotrophin receptor variably expressed in melanoma. While contradictory data are reported on its role as a marker of tumor initiating cells, little is known on its function in tumor progression. CD271 expression was higher in spheroids derived from freshly isolated cells of primary melanomas and in primary WM115 and WM793-B cell lines, while it decreased during progression to advanced stages in cells isolated from metastatic melanomas and in metastatic WM266-4 and 1205Lu cell lines. Moreover, CD271 was scarcely detected in the highly invasive spheroids (SKMEL28 and 1205Lu). CD271, originally expressed in the epidermis of skin reconstructs, disappeared when melanoma started to invade the dermis. SKMEL8 CD271(-) cells showed greater proliferation and invasiveness in vitro, and were associated with a higher number of metastases in zebrafish, as compared to CD271(+) cells. CD271 silencing in WM115 induced a more aggressive phenotype in vitro and in vivo. On the contrary, CD271 overexpression in SKMEL28 cells reduced invasion in vitro, and CD271 overexpressing 1205Lu cells was associated with a lower percentage of metastases in zebrafish. A reduced cell-cell adhesion was also observed in absence of CD271. Taken together, these results indicate that CD271 loss is critical for melanoma progression and metastasis

Thermal patterning of superconducting films

Includes bibliographical references (page 600).The transient shape control of a superconducting high Tc film by selective optical heating has been addressed in this work, using a non-conventional technique that combines the application of a pulsed magnetic field and the optical heating of the superconducting film by a synchronized pulsed laser. A zero field cooled (ZFC) film was partially protected by a mask before exposing it to the laser radiation. The temperature at the illuminated area rises causing very fast local lowering of the vortex pinning force or may even rise above Tc. As a result, flux penetrates completely the heated area and an effective smaller sample remains in a superconducting critical state. Flux penetration is measured with a pick-up coil for different positions of the mask. Results are described within the critical state model for a strip, where the time integrated voltage signal is approximated to the flux difference between the initial ZFC sample and the final critical state of the "new" (cold) ZFC sample

Design of a fluorescence technique using double laser pulse excitation for the measurement of molecular Brownian dynamics

Includes bibliographical references (page 234).A complete analysis of a novel method to evaluate the rotational diffusion time of fluorescent molecules is presented. It is based on the study of the total fluorescence produced after excitation with two consecutive short laser pulses. Expressions for the total fluorescence energy emitted in this case are derived, which would allow the evaluation of the rotational diffusion time. The main advantages of the proposed method are its simple setup, a time resolution only limited by the exciting laser pulsewidth, and the fact that it does not require fast time response detectors

Short pulse generation in solid state lasers by a novel passive technique

Includes bibliographical references (page 216).A novel passive Q-switching technique based on self-focusing is studied theoretically and experimentally. In this paper we present results obtained with a simple aberrationless gaussian model that describes the short pulse generation dynamics for different cavity configurations and different nonlinear characteristics of the focusing medium. Experimental results are also presented that are in good agreement with the predictions of the theoretical model. Preliminary results in ultrashort pulse generation are also presented

Do DLX3 and CD271 Protect Human Keratinocytes from Squamous Tumor Development?

Well-regulated epidermal homeostasis depends on the function of different classes of factors, such as transcription regulators and receptors. Alterations in this homeostatic balance may lead to the development of cutaneous squamous tumorigenesis. The homeobox transcription factor DLX3 is determinant for a p53-dependent regulation of epidermal differentiation and modulates skin carcinogenesis. The maintenance of skin homeostasis also involves the action of neurotrophins (NTs) and their receptors, Trk and CD271. While Trk receptor overexpression is a hallmark of cancer, there are conflicting data on CD271 expression and function in cutaneous SCC (cSCC). Previous studies have reported NT receptors expression in head and neck SSC (HNSCC). We show that CD271 is expressed at low levels in primary cSCC cells and the number of CD271+ cells correlates with cell cohesion in SCC spheroids. In normal epidermis, CD271 is expressed in proliferative progenitor cells and DLX3 in terminally differentiated keratinocytes. Brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) increase DLX3 expression. In the absence of a functional BDNF receptor TrkB in keratinocytes, we hypothesize that the BDNF-dependent DLX3 response could be mediated via CD271. Altogether, our results support a putative CD271-DLX3 connection in keratinocytes, which might be crucial to preventing squamous skin cancer

Structured Prediction for CRiSP Inverse Kinematics Learning with Misspecified Robot Models

With the recent advances in machine learning, problems that traditionally would require accurate modeling to be solved analytically can now be successfully approached with data-driven strategies. Among these, computing the inverse kinematics of a redundant robot arm poses a significant challenge due to the non-linear structure of the robot, the hard joint constraints and the non-invertible kinematics map. Moreover, most learning algorithms consider a completely data-driven approach, while often useful information on the structure of the robot is available and should be positively exploited. In this work, we present a simple, yet effective, approach for learning the inverse kinematics. We introduce a structured prediction algorithm that combines a data-driven strategy with the model provided by a forward kinematics function -- even when this function is misspecified -- to accurately solve the problem. The proposed approach ensures that predicted joint configurations are well within the robot's constraints. We also provide statistical guarantees on the generalization properties of our estimator as well as an empirical evaluation of its performance on trajectory reconstruction tasks.Comment: Accepted for publication in IEEE Robotics and Automation Letters (2021) and presentation at IEEE International Conference on Robotics and Automation (2021) Updated funding informatio