Advanced workstations and collaborative robots: exploiting eye-tracking and cardiac activity indices to unveil senior workers' mental workload in assembly tasks.

Introduction: As a result of Industry 5.0's technological advancements, collaborative robots (cobots) have emerged as pivotal enablers for refining manufacturing processes while re-focusing on humans. However, the successful integration of these cutting-edge tools hinges on a better understanding of human factors when interacting with such new technologies, eventually fostering workers' trust and acceptance and promoting low-fatigue work. This study thus delves into the intricate dynamics of human-cobot interactions by adopting a human-centric view. Methods: With this intent, we targeted senior workers, who often contend with diminishing work capabilities, and we explored the nexus between various human factors and task outcomes during a joint assembly operation with a cobot on an ergonomic workstation. Exploiting a dual-task manipulation to increase the task demand, we measured performance, subjective perceptions, eye-tracking indices and cardiac activity during the task. Firstly, we provided an overview of the senior workers' perceptions regarding their shared work with the cobot, by measuring technology acceptance, perceived wellbeing, work experience, and the estimated social impact of this technology in the industrial sector. Secondly, we asked whether the considered human factors varied significantly under dual-tasking, thus responding to a higher mental load while working alongside the cobot. Finally, we explored the predictive power of the collected measurements over the number of errors committed at the work task and the participants' perceived workload. Results: The present findings demonstrated how senior workers exhibited strong acceptance and positive experiences with our advanced workstation and the cobot, even under higher mental strain. Besides, their task performance suffered increased errors and duration during dual-tasking, while the eye behavior partially reflected the increased mental demand. Some interesting outcomes were also gained about the predictive power of some of the collected indices over the number of errors committed at the assembly task, even though the same did not apply to predicting perceived workload levels. Discussion: Overall, the paper discusses possible applications of these results in the 5.0 manufacturing sector, emphasizing the importance of adopting a holistic human-centered approach to understand the human-cobot complex better.

ATM kinase activity modulates cFLIP protein levels: potential interplay between DNA damage signalling and TRAIL-induced apoptosis.

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has been proposed as a potent tool to trigger apoptosis in cancer therapy. However, since ∼60% of tumour cell lines and most primary cancers are resistant to TRAIL-induced apoptosis, several combined therapy approaches aimed to sensitize cells to TRAIL have been developed. One of the major targets of these approaches are cFLIP proteins as they interfere with the initiation of apoptosis induction by TRAIL, are over-expressed in many cancers and their down-regulation enhances TRAIL sensitivity. Although, DNA-damaging agents such as 5-fluorouracil (5-FU), etoposide and adriamycin have been successfully employed due to their ability to trigger cFLIP(L) and cFLIP(s) down-regulation the molecular mechanisms underneath their action have been only partially elucidated. We have recently identified ataxia telangiectasia mutated (ATM) as a modulator of cFLIP(L) and cFLIP(S) protein levels in the DNA damage response. Here, we provide genetic evidence that ATM kinase activity is required to trigger 5-FU- and neocarzinostatin-dependent cFLIP(L) and cFLIP(S) down-regulation, which in turn sensitize hepatocellular carcinoma (HCC) cell lines to TRAIL. ATM activity triggers cFLIP proteins down-regulation in HCC cells independently on p53 and enhances cFLIP(L) ubiquitination in response to DNA damage. Therefore, we propose that ATM kinase mediates the interplay between DNA damage and death receptor signalling and suggest that expression of catalytically competent ATM in tumour cells may play a key role for successful combinatorial use of TRAIL receptor agonists and DNA-damaging drugs in cancer therapy.

Proteomic profiling of ATM kinase proficient and deficient cell lines upon blockage of proteasome activity.

Ataxia Telangiectasia Mutated (ATM) protein kinase is a key effector in the modulation of the functionality of some important stress responses, including DNA damage and oxidative stress response, and its deficiency is the hallmark of Ataxia Telangiectasia (A-T), a rare genetic disorder. ATM modulates the activity of hundreds of target proteins, essential for the correct balance between proliferation and cell death. The aim of this study is to evaluate the phenotypic adaptation at the protein level both in basal condition and in presence of proteasome blockage in order to identify the molecules whose level and stability are modulated through ATM expression. We pursued a comparative analysis of ATM deficient and proficient lymphoblastoid cells by label-free shotgun proteomic experiments comparing the panel of proteins differentially expressed. Through a non-supervised comparative bioinformatic analysis these data provided an insight on the functional role of ATM deficiency in cellular carbohydrate metabolism's regulation. This hypothesis has been demonstrated by targeted metabolic fingerprint analysis SRM (Selected Reaction Monitoring) on specific thermodynamic checkpoints of glycolysis. This article is part of a Special Issue entitled: Translational Proteomics.

c-Abl acetylation by histone acetyltransferases regulates its nuclear-cytoplasmic localization.

c-Abl function is strictly dependent on its subcellular localization. Using an in vitro approach, we identify c-Abl as a new substrate for p300, CBP (CREB-binding protein) and PCAF (p300/CBP-associated factor) histone acetyltransferases. Remarkably, acetylation markedly alters its subcellular localization. Point mutagenesis indicated that Lys 730, located in the second nuclear localization signal, is the main target of p300 activity. It has previously been reported that c-Abl accumulates in the cytoplasm during myogenic differentiation. Here, we show that c-Abl protein is acetylated at early stages of myogenic differentiation. Indeed, acetylation on Lys 730 drives c-Abl accumulation in the cytoplasm and promotes differentiation. Thus, Lys 730 acetylation is a novel post-translational modification of c-Abl and a novel mechanism for modulating its subcellular localization that contributes to myogenic differentiation.