The multiform motor cortical output: kinematic, predictive and response coding

Observing actions performed by others entails a subliminal activation of primary motor cortex reflecting the components encoded in the observed action. One of the most debated issues concerns the role of this output: Is it a mere replica of the incoming flow of information (kinematic coding), is it oriented to anticipate the forthcoming events (predictive coding) or is it aimed at responding in a suitable fashion to the actions of others (response coding)? The aim of the present study was to disentangle the relative contribution of these three levels and unify them into an integrated view of cortical motor coding. We combined transcranial magnetic stimulation (TMS) and electromyography recordings at different timings to probe the excitability of corticospinal projections to upper and lower limb muscles of participants observing a soccer player performing: (i) a penalty kick straight in their direction and then coming to a full stop, (ii) a penalty kick straight in their direction and then continuing to run, (iii) a penalty kick to the side and then continuing to run. The results show a modulation of the observer's corticospinal excitability in different effectors at different times reflecting a multiplicity of motor coding. The internal replica of the observed action, the predictive activation, and the adaptive integration of congruent and non-congruent responses to the actions of others can coexist in a not mutually exclusive way. Such a view offers reconciliation among different (and apparently divergent) frameworks in action observation literature, and will promote a more complete and integrated understanding of recent findings on motor simulation, motor resonance and automatic imitation

Lentiviral Hematopoietic Stem Cell Gene Therapy in Patients with Wiskott-Aldrich Syndrome.

iskott-Aldrich syndrome (WAS) is an inherited immunodeficiency caused by mutations in the gene encoding WASP, a protein regulating the cytoskeleton. Hematopoietic stem/progenitor cell (HSPC) transplants can be curative, but, when matched donors are unavailable, infusion of autologous HSPCs modified ex vivo by gene therapy is an alternative approach. We used a lentiviral vector encoding functional WASP to genetically correct HSPCs from three WAS patients and reinfused the cells after a reduced-intensity conditioning regimen. All three patients showed stable engraftment of WASP-expressing cells and improvements in platelet counts, immune functions, and clinical scores. Vector integration analyses revealed highly polyclonal and multilineage haematopoiesis resulting from the gene-corrected HSPCs. Lentiviral gene therapy did not induce selection of integrations near oncogenes, and no aberrant clonal expansion was observed after 20 to 32 months. Although extended clinical observation is required to establish long-term safety, lentiviral gene therapy represents a promising treatment for WAS

Cortical Representation of Lateralized Grasping in Chimpanzees (Pan troglodytes): A Combined MRI and PET Study

Functional imaging studies in humans have localized the motor-hand region to a neuroanatomical landmark call the KNOB within the precentral gyrus. It has also been reported that the KNOB is larger in the hemisphere contralateral to an individual's preferred hand, and therefore may represent the neural substrate for handedness. The KNOB has also been neuronatomically described in chimpanzees and other great apes and is similarly associated with handedness. However, whether the chimpanzee KNOB represents the hand region is unclear from the extant literature. Here, we used PET to quantify neural metabolic activity in chimpanzees when engaged in unilateral reach-and-grasping responses and found significantly lateralized activation of the KNOB region in the hemisphere contralateral to the hand used by the chimpanzees. We subsequently constructed a probabilistic map of the KNOB region in chimpanzees in order to assess the overlap in consistency in the anatomical landmarks of the KNOB with the functional maps generated from the PET analysis. We found significant overlap in the anatomical and functional voxels comprising the KNOB region, suggesting that the KNOB does correspond to the hand region in chimpanzees. Lastly, from the probabilistic maps, we compared right- and left-handed chimpanzees on lateralization in grey and white matter within the KNOB region and found that asymmetries in white matter of the KNOB region were larger in the hemisphere contralateral to the preferred hand. These results suggest that neuroanatomical asymmetries in the KNOB likely reflect changes in connectivity in primary motor cortex that are experience dependent in chimpanzees and possibly humans

The stain of the original salt: Red heats on chrome tanned leathers and Purple spots on ancient parchments are two sides of the same ecological coin

Animal hides are one of man’s earliest and mostly used materials; many rawhide products, primarily leather, have for centuries been used for several purposes. The peculiar mechanical properties of leather depend on the hide composition, a dense collagen feltwork. Unfortunately, due to their proteic composition, rawhides may undergo microbial attack and biodeterioration. Over centuries, different processes and treatments (brining, vegetal or chrome tanning, tawing, etc.) were set up to face the biological attack and modify/stabilise the hide’s mechanical properties. Nevertheless, even present-day rawhides are subjected to biological colonisation, and traces of this colonisation are clearly shown in Chrome(III) tanned leathers (in the wet blue stage), with obvious economic damages. The colonisation traces on tanned leathers consist of isolated or coalescent red patches, known as red heat deterioration. Parchments are rawhide products, too; they derive from another manufacturing procedure. Even parchments undergo microbial attack; the parchment biodeterioration seems comparable to leather red heat deterioration and is known as purple spots. Recently, an ecological succession model explained the process of historical parchment purple spot deterioration; the haloarchaea Halobacterium salinarum is the pioneer organism triggering this attack. The marine salt used to prevent rawhide rotting is the carrier of haloarchaea colonisers (Migliore et al., 2019). The aim of this study was to investigate the dynamics of biodeterioration on Chrome(III) tanned leathers and its effects on the stability/integrity of collagen structure. To this end, standard cultivation methods were integrated with three updated technologies, Next-Generation Sequencing (NGS), Raman spectroscopy, and Light Transmitted Analysis (LTA). A bioinformatic comparison between chrome tanned leather vs. historical parchment colonisers was performed to evaluate if leather and parchment share common culprits; furthermore, the effect of the biodeterioration on the physical properties of the hide product was evaluated

Wiskott-Aldrich Syndrome protein deficiency perturbs the homeostasis of B-cell compartment in humans

Wiskott-Aldrich Syndrome protein (WASp) regulates the cytoskeleton in hematopoietic cells and mutations in its gene cause the Wiskott-Aldrich Syndrome (WAS), a primary immunodeficiency with microthrombocytopenia, eczema and a higher susceptibility to develop tumors. Autoimmune manifestations, frequently observed in WAS patients, are associated with an increased risk of mortality and still represent an unsolved aspect of the disease. B cells play a crucial role both in immune competence and self-tolerance and defects in their development and function result in immunodeficiency and/or autoimmunity. We performed a phenotypical and molecular analysis of central and peripheral B-cell compartments in WAS pediatric patients. We found a decreased proportion of immature B cells in the bone marrow correlating with an increased presence of transitional B cells in the periphery. These results could be explained by the defective migratory response of WAS B cells to SDF-1alpha, essential for the retention of immature B cells in the BM. In the periphery, we observed an unusual expansion of CD21low B-cell population and increased plasma BAFF levels that may contribute to the high susceptibility to develop autoimmune manifestations in WAS patients. WAS memory B cells were characterized by a reduced in vivo proliferation, decreased somatic hypermutation and preferential usage of IGHV4-34, an immunoglobulin gene commonly found in autoreactive B cells. In conclusion, our findings demonstrate that WASp-deficiency perturbs B-cell homeostasis thus adding a new layer of immune dysregulation concurring to the increased susceptibility to develop autoimmunity in WAS patient