Understanding motor planning and action recognition of pantomimed grasps

The ability to manipulate objects with considerable skill is one of the defining features of primates. In both humans and non-human primates, grasping is typically directed toward a visible object and results in contact with the object. Humans - and perhaps some other species - are also capable of grasping imaginary objects in a pantomimed prehension. Pantomimed grasps are well studied, both for theoretical and clinical interests, to explore the double function of human hands, as instrumental as well as communicative devices. The present thesis aims to investigate both aspects of pantomimed grasps in terms of motor control, action understanding and neural activation during action observation. The first experiment explored whether the way pantomimed grasps are executed can convey weight information of imaginary objects. The second experiment tested whether observers can exploit movement kinematics to discriminate between real (i.e., movements directed toward a physically present object) and pantomimed grasps. The third study investigated if perception of real and pantomimed grasps might automatically drive object representation. The fourth experiment inspected whether having a motor expertise on pantomimed grasp execution impacts pantomimed grasp processing. The fifth experiment shed new insights on the neural underpinnings of action understanding mechanisms by exploring electroencephalography (EEG) signals during real and pantomimed grasp observation

CD38 and bone marrow microenvironment.

This review summarizes the events ruled by CD38 shaping the bone marrow environment, recapitulating old and new aspects derived from the body of knowledge on the molecule. The disease models considered were myeloma and chronic lymphocytic leukemia (CLL). CD38 has been analyzed considering its twin function as receptor and enzyme, roles usually not considered in clinics, where it is used as a routine marker. Another aspect pertaining basic science concerns the role of the molecule as a member of an ectoenzyme network, potentially metabolizing soluble factors not yet analyzed (e.g., NAD+, ATP, NAM) or influencing hormone secretion (e.g., oxytocin). The last point is focused on the use of CD38 as a target of an antibody-mediated therapeutic approach in myeloma and CLL. A recent observation is that CD38 may run an escape circuit leading to the production of adenosine. The generation of local anergy may be blocked by using anti-CD38 antibodies. Consequently, not only might CD38 be a prime target for mAb-mediated therapy, but its functional block may contribute to general improvement in cancer immunotherapy and outcomes

Cytokine-induced killer cells express CD39, CD38, CD203a, CD73 ectoenzymes and P1 adenosinergic receptors

Cytokine-induced killer (CIK) cells, a heterogeneous T cell population obtained by in vitro differentiation of peripheral blood mononuclear cells (PBMC), represent a promising immunological approach in cancer. Numerous studies have explored the role of CD38, CD39, CD203a/PC-1, and CD73 in generating extracellular adenosine (ADO) and thus in shaping the tumor niche in favor of proliferation. The findings shown here reveal that CIK cells are able to produce extracellular ADO via traditional (CD39/CD73) and/or alternative (CD38/CD203a/CD73 or CD203a/CD73) pathways. Transcriptome analysis showed the mRNA expression of these molecules and their modulation during PBMC to CIK differentiation. When PBMC from normal subjects or cancer bearing patients were differentiated into CIK cells under normoxic conditions, CD38 and CD39 were greatly up-regulated while the number of CD203a, and CD73 positive cells underwent minor changes. Since hypoxic conditions are often found in tumors, we asked whether CD39, CD38, CD203a, and CD73 expressed by CIK cells were modulated by hypoxia. PBMC isolated from cancer patients and differentiated into CIK cells in hypoxic conditions did not show relevant changes in CD38, CD39, CD73, CD203a, and CD26. CIK cells also expressed A1, A2A, and A2B ADO receptors and they only underwent minor changes as a consequence of hypoxia. The present study sheds light on a previously unknown functional aspect of CIK cells, opening the possibility of pharmacologically modulated ADO-generating ectoezymes to improve CIK cells performance

CD38 promotes pristane-induced chronic inflammation and increases susceptibility to experimental lupus by an apoptosis-driven and TRPM2-dependent mechanism

In this study, we investigated the role of CD38 in a pristane-induced murine model of lupus. CD38-deficient (Cd38-/-) but not ART2-deficient (Art2-/-) mice developed less severe lupus compared to wild type (WT) mice, and their protective phenotype consisted of (i) decreased IFN-I-stimulated gene expression, (ii) decreased numbers of peritoneal CCR2hiLy6Chi inflammatory monocytes, TNF-α-producing Ly6G+ neutrophils and Ly6Clo monocytes/macrophages, (iii) decreased production of anti-single-stranded DNA and anti-nRNP autoantibodies, and (iv) ameliorated glomerulonephritis. Cd38-/- pristane-elicited peritoneal exudate cells had defective CCL2 and TNF-α secretion following TLR7 stimulation. However, Tnf-α and Cxcl12 gene expression in Cd38-/- bone marrow (BM) cells was intact, suggesting a CD38-independent TLR7/TNF-α/CXCL12 axis in the BM. Chemotactic responses of Cd38-/- Ly6Chi monocytes and Ly6G+ neutrophils were not impaired. However, Cd38-/- Ly6Chi monocytes and Ly6Clo monocytes/macrophages had defective apoptosis-mediated cell death. Importantly, mice lacking the cation channel TRPM2 (Trpm2-/-) exhibited very similar protection, with decreased numbers of PECs, and apoptotic Ly6Chi monocytes and Ly6Clo monocytes/macrophages compared to WT mice. These findings reveal a new role for CD38 in promoting aberrant inflammation and lupus-like autoimmunity via an apoptosis-driven mechanism. Furthermore, given the implications of CD38 in the activation of TRPM2, our data suggest that CD38 modulation of pristane-induced apoptosis is TRPM2-dependent.We would like to thank Dr. Yasuo Mori for providing the Tr pm 2−/− mice, Clara Sánchez for animal husbandry at the IPBLN-CSIC Animal Facility, and Thomas S. Simpler and Uma Mudunuru for animal husbandry at the University of Alabama at Birmingham (UAB). We would also like to thank Laura Montosa from the Centro de Instrumentación Cientifica (CIC) at the Universidad de Granada (UGR) for technical support with microscopy, as well as Mohamed Tassi and Ana Santos at CIC, UGR, and Sandra García-Jiménez, Victoria Romero-del-Amo, Gemma Palencia-López, and Samuel Ruiz-Santiago at Campus Formación Granada for tissue preparations, H&E staining, and other staining procedures. Work performed in the Sancho lab was supported in part by the European Commission in collaboration with the following Funding Agencies: (i) Junta de Andalucía (J.A.), Consejería Innovación Ciencia y Empresa y Consejería Educación y Ciencia, Project: PC08-CTS-04046 to J.S. and M.Z., and (ii) Ministerio de Economía y Competitividad (MINECO), Projects: SAF-2011-27261 to J.S. and M.Z. and SAF2014-55088-R to R.M. Work performed in the Lund lab was supported by funds provided by UAB.S

Roles and modalities of ectonucleotidases in remodeling the multiple myeloma niche

Ectoenzymes are cell surface molecules, which represent functional bridges between the environment and the cytoplasm. One set of ectoenzymes-CD39, CD38, CD203a, and CD73-leads to the generation of adenosine (ADO) by metabolizing ATP and NAD+. While ADO is known to control inflammation and suppress immune responses, other aspects of ADO function are still obscure, mainly due to its short half-life in biological fluids. Human multiple myeloma (MM) grows in the closed system of the bone marrow (BM) niche representing an ideal setting for studying ectoenzymes and their products. Another source of information on ectoenzyme function may derive from in vivo results of anti-CD38 antibody therapy in MM. Current results, obtained from in vitro models and from preliminary in vivo findings, indicate that ectoenzymes produce ADO locally in the BM niche. Furthermore, MM cells release microvesicles (MV), which thanks to their molecular cargo and surface ectoenzymes may function as particulate communicators outside of the niche. During anti-CD38 antibody therapy, the MV carry therapeutic IgG, determining that the prevalent orientation of MV will be toward cells and tissues expressing receptors for the IgG Fc domain. The resulting picture is one where MM adopts an immune escape strategy based on reshaping the environmental niche. This adaptation is followed by actions of MV that are exerted in biological fluids and circulating immune cells. By coating FcRs+cells, MV modify pericellular spaces, reproducing the metabolic halo generated by ectoenzymes within closed systems

Preventing action slows down performance in perceptual judgment

Action and vision are known to be tightly coupled with each other. In a previous study, we found that repeatedly grasping an object without any visual feedback might result in a perceptual aftereffect when the object was visually presented in the context of a perceptual judgement task. In this study, we explored whether and how such an effect could be modulated by presenting the object behind a transparent barrier. Our conjecture was that if perceptual judgment relies, in part at least, on the same processes and representations as those involved in action, then one should expect to find a slowdown in judgment performance when the target object looks to be out of reach. And this was what we actually found. This indicates that not only acting upon an object but also being prevented from acting upon it can affect how the object is perceptually judged