Two brains in action: joint-action coding in the primate frontal cortex

Daily life often requires the coordination of our actions with those of another partner. After sixty years (1968-2018) of behavioral neurophysiology of motor control, the neural mechanisms which allow such coordination in primates are unknown. We studied this issue by recording cell activity simultaneously from dorsal premotor cortex (PMd) of two male interacting monkeys trained to coordinate their hand forces to achieve a common goal. We found a population of 'joint-action cells' that discharged preferentially when monkeys cooperated in the task. This modulation was predictive in nature, since in most cells neural activity led in time the changes of the "own" and of the "other" behavior. These neurons encoded the joint-performance more accurately than 'canonical action-related cells', activated by the action per se, regardless of the individual vs. interactive context. A decoding of joint-action was obtained by combining the two brains activities, using cells with directional properties distinguished from those associated to the 'solo' behaviors. Action observation-related activity studied when one monkey observed the consequences of the partner's behavior, i.e. the cursor's motion on the screen, did not sharpen the accuracy of 'joint-action cells' representation, suggesting that it plays no major role in encoding joint-action. When monkeys performed with a non-interactive partner, such as a computer, 'joint-action cells' representation of the "other" (non-cooperative) behavior was significantly degraded. These findings provide evidence of how premotor neurons integrate the time-varying representation of the self-action with that of a co-actor, thus offering a neural substrate for successful visuo-motor coordination between individuals.SIGNIFICANT STATEMENTThe neural bases of inter-subject motor coordination were studied by recording cell activity simultaneously from the frontal cortex of two interacting monkeys, trained to coordinate their hand forces to achieve a common goal. We found a new class of cells, preferentially active when the monkeys cooperated, rather than when the same action was performed individually. These 'joint-action neurons' offered a neural representation of joint-behaviors by far more accurate than that provided by the canonical action-related cells, modulated by the action per se regardless of the individual/interactive context. A neural representation of joint-performance was obtained by combining the activity recorded from the two brains. Our findings offer the first evidence concerning neural mechanisms subtending interactive visuo-motor coordination between co-acting agents

Extensive reuse of soda-lime waste glass in fly ash-based geopolymers

The possibility of extensive incorporation of soda-lime waste glass in the synthesis of fly ash-based geopolymers was investigated. Using waste glass as silica supplier avoids the use of water glass solution as chemical activator. The influence of the addition of waste glass on the microstructure and strength of fly ash-based geopolymers was studied through microstructural and mechanical characterization. Leaching analyses were also carried out. The samples were developed changing the SiO2/Al2O3 molar ratio and the molarity of the sodium hydroxide solution used as alkaline activator. The results suggest that increasing the amount of waste glass as well as increasing the molarity of the solution lead to the formation of zeolite crystalline phases and an improvement of the mechanical strength. Leaching results confirmed that the new geopolymers have the capability to immobilize heavy metal ions

Alamethicin self-assembling in lipid membranes: concentration dependence from pulsed EPR of spin labels

The antimicrobial action of the peptide antibiotic alamethicin (Alm) is commonly related to peptide self-assembling resulting in the formation of voltage-dependent channels in bacterial membranes, which induces ion permeation. To obtain a deeper insight into the mechanism of channel formation, it is useful to know the dependence of self-assembling on peptide concentration. With this aim, we studied Alm F50/5 spin-labeled analogs in a model 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membrane, for peptide-to-lipid (P/L) ratios varying between 1/1500 and 1/100. Pulsed electron-electron double resonance (PELDOR) spectroscopy reveals that even at the lowest concentration investigated, the Alm molecules assemble into dimers. Moreover, under these conditions, electron spin echo envelope modulation (ESEEM) spectroscopy of D2O-hydrated membranes shows an abrupt change from the in-plane to the trans-membrane orientation of the peptide. Therefore, we hypothesize that dimer formation and peptide reorientation are concurrent processes and represent the initial step of peptide self-assembling. By increasing peptide concentration, higher oligomers are formed. A simple kinetic model of equilibrium among monomers, dimers, and pentamers allows for satisfactorily describing the experimental PELDOR data. The inter-label distances in the oligomers obtained from PELDOR experiments become better resolved with increasing P/L ratio, thus suggesting that the supramolecular organization of the higher-order oligomers becomes more defined

JAK2-STAT5 signaling: A novel mechanism of resistance to targeted PI3K/mTOR inhibition

A recent article published by Britschgi et al. in Cancer Cell, “JAK2/STAT5 Inhibition Circumvents Resistance to PI3K/mTOR Blockade: A Rationale for Cotargeting These Pathways in Metastatic Breast Cancer,” describes a positive feedback loop of JAK2/STAT5 activation that drives resistance to PI3K/mTOR inhibition in breast cancer. The authors found that genetic or pharmacological inhibition of JAK2 circumvents resistance to PI3K/mTOR inhibition and go on to show the efficacy of combined PI3K/mTOR and JAK2 inhibition on reducing cancer cell number, tumor growth, and metastasis as well as increasing in vivo survival. These results provide strong support for combination therapy with JAK2/STAT5 and PI3K/mTOR inhibitors in breast cancer. Here we discuss how the article by Britschgi et al. proposes a novel mechanism to explain how breast cancer cells overcome inhibition of a key signaling pathway driving cell proliferation. We also discuss the interplay between activation of the transcription factors STAT5 and STAT3 in breast cancer