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Attention is needed to perform goal-directed vision-guided movements. We investigated whether the direction of covert attention modulates movement outcomes and dynamics. Right-handed and left-handed volunteers attended to a spatial location while planning a reach toward the same hemifield, the opposite one, or planned a reach without constraining attention. We measured behavioral variables as outcomes of ipsilateral and contralateral reaching and the tangling of behavioral trajectories obtained through principal component analysis as a measure of the dynamics of motor control. We found that the direction of covert attention had significant effects on the dynamics of motor control, specifically during contralateral reaching. Data suggest that motor control was more feedback-driven when attention was directed leftward than when attention was directed rightward or when it was not constrained, irrespectively of handedness. These results may help to better understand the neural bases of asymmetrical neurological diseases like hemispatial neglect.

The interplay between attention, alertness, and motor planning is crucial for our manual interactions. To investigate the neural bases of this interaction and challenge the views that attention cannot be disentangled from motor planning, we instructed human volunteers of both sexes to plan and execute reaching movements while attending to the target, while attending elsewhere, or without constraining attention. We recorded reaction times to reach initiation and pupil diameter and interfered with the functions of the medial posterior parietal cortex (mPPC) with online repetitive transcranial magnetic stimulation to test the causal role of this cortical region in the interplay between spatial attention and reaching. We found that mPPC plays a key role in the spatial association of reach planning and covert attention. Moreover, we have found that alertness, measured by pupil size, is a good predictor of the promptness of reach initiation only if we plan a reach to attended targets, and mPPC is causally involved in this coupling. Different from previous understanding, we suggest that mPPC is neither involved in reach planning per se, nor in sustained covert attention in the absence of a reach plan, but it is specifically involved in attention functional to reaching. [ABSTRACT FROM AUTHOR]

Attention is needed to perform goal-directed vision-guided movements. We investigated whether the direction of covert attention modulates movement outcomes and dynamics. Right-handed and left-handed volunteers attended to a spatial location while planning a reach toward the same hemifield, the opposite one, or planned a reach without constraining attention. We measured behavioral variables as outcomes of ipsilateral and contralateral reaching and the tangling of behavioral trajectories obtained through principal component analysis as a measure of the dynamics of motor control. We found that the direction of covert attention had significant effects on the dynamics of motor control, specifically during contralateral reaching. Data suggest that motor control was more feedback-driven when attention was directed leftward than when attention was directed rightward or when it was not constrained, irrespectively of handedness. These results may help to better understand the neural bases of asymmetrical neurological diseases like hemispatial neglect. [ABSTRACT FROM AUTHOR]

Introduction: β-thalassemia is caused by autosomal mutations in the β-globin gene, which induce the absence or low-level synthesis of β-globin in erythroid cells. It is widely accepted that a high production of fetal hemoglobin (HbF) is beneficial for patients with β-thalassemia. Sirolimus, also known as rapamycin, is a lipophilic macrolide isolated from a strain of Streptomyces hygroscopicus that serves as a strong HbF inducer in vitro and in vivo . In this study, we report biochemical, molecular, and clinical results of a sirolimus-based NCT03877809 clinical trial (a personalized medicine approach for β-thalassemia transfusion-dependent patients: testing sirolimus in a first pilot clinical trial, Sirthalaclin). Methods: Accumulation of γ-globin mRNA was analyzed using reverse-transcription quantitative polymerase chain reaction (PCR), while the hemoglobin pattern was analyzed using high-performance liquid chromatography (HPLC). The immunophenotype was analyzed using a fluorescence-activated cell sorter (FACS), with antibodies against CD3, CD4, CD8, CD14, CD19, CD25 (for analysis of peripheral blood mononuclear cells), or CD71 and CD235a (for analysis of in vitro cultured erythroid precursors). Results: The results were obtained in eight patients with the β + /β + and β + /β 0 genotypes, who were treated with a starting dosage of 1 mg/day sirolimus for 24–48 weeks. The first finding of this study was that the expression of γ-globin mRNA increased in the blood and erythroid precursor cells isolated from β-thalassemia patients treated with low-dose sirolimus. This trial also led to the important finding that sirolimus influences erythropoiesis and reduces biochemical markers associated with ineffective erythropoiesis (excess free α-globin chains, bilirubin, soluble transferrin receptor, and ferritin). A decrease in the transfusion demand index was observed in most (7/8) of the patients. The drug was well tolerated, with minor effects on the immunophenotype, and an only side effect of frequently occurring stomatitis. Conclusion: The data obtained indicate that low doses of sirolimus modify hematopoiesis and induce increased expression of γ-globin genes in a subset of patients with β-thalassemia. Further clinical trials are warranted, possibly including testing of the drug in patients with less severe forms of the disease and exploring combination therapies.

The pandemic caused by the SARS-CoV-2 virus (COVID-19) is still a major health issue. The COVID-19 pandemic has forced the university teaching to consider in high priority the switch from in-presence teaching to remote teaching, including laboratory teaching. While excellent virtual-laboratory teaching has been proposed and turned out to be very useful, the need of a real-laboratory in-presence teaching is still a major need. This study was aimed at presenting a laboratory exercise focusing (a) on a very challenging therapeutic strategy, i.e. SARS-CoV-2 diagnostics, and (b) on technologies that are playing a central role in applied biochemistry and molecular biology, i.e. PCR and RT-PCR. The aims of the practical laboratory were to determine: (a) the possibility to identify SARS-CoV-2 sequences starting from a recombinant plasmid and (b) the possibility to discriminate cells with respect to the expression of SARS-CoV-2 Spike protein. This activity is simple (cell culture, RNA extraction, RT-qPCR are all well-established technologies), fast (starting from isolated and characterized RNA, few hours are just necessary), highly reproducible (therefore easily employed by even untrained students). We suggest that this laboratory practical exercises should be considered for face-to-face teaching especially if the emergency related to the COVID-19 pandemic is maintained. The teaching protocol here described might be considered in order to perform fast but meaningful in-presence teaching, making feasible the division of crowded classes in low-number cohorts of students, allowing the maintenance of the required social distance.

The external bonding of carbon fiber-reinforced polymer (CFRP) strips by two-component epoxy adhesive on the concrete surfaces of buildings and bridges is a retrofitting method accepted worldwide. The gradient anchorage (GA) is an anchoring method especially developed to anchor prestressed CFRP strips to concrete elements without a need for mechanical clamping after the installation phase. This method takes advantage of the adhesives property to undergo accelerated curing when heated. The results of more than fifteen years of research on the development of the gradient anchorage at the Swiss Federal Laboratories for Materials Science and Technology (Empa) are presented in this paper. The basic principles and application steps are explained, and the main results starting from the development of the technique up to the testing of real scale girders are described, and the new challenges posed by this innovative system are highlighted. The gradient anchorage is a valid alternative to a mechanically anchored system for prestressed FRP (P-FRP).

Abstract Over the years, electrophysiological recordings in macaque monkeys performing visuomotor tasks brought about accumulating evidence for the expression of neuronal properties (e.g., selectivity in the visuospatial and somatosensory domains, encoding of visual affordances and motor cues) in the posterior parietal area V6A that characterize it as an ideal neural substrate for online control of prehension. Interestingly, neuroimaging studies suggested a role of putative human V6A also in action preparation; moreover, pre-movement population activity in monkey V6A has been recently shown to convey grip-related information for upcoming grasping. Here we directly test whether macaque V6A neurons encode preparatory signals that effectively differentiate between dissimilar actions before movement. We recorded the activity of single V6A neurons during execution of two visuomotor tasks requiring either reach-to-press or reach-to-grasp movements in different background conditions, and described the nature and temporal dynamics of V6A activity preceding movement execution. We found striking consistency in neural discharges measured during pre-movement and movement epochs, suggesting that the former is a preparatory activity exquisitely linked to the subsequent execution of particular motor actions. These findings strongly support a role of V6A beyond the online guidance of movement, with preparatory activity implementing suitable motor programs that subsequently support action execution.

Abstract Background Nonsense mutations promote premature translational termination, introducing stop codons within the coding region of mRNAs and causing inherited diseases, including thalassemia. For instance, in β039 thalassemia the CAG (glutamine) codon is mutated to the UAG stop codon, leading to premature translation termination and to mRNA destabilization through the well described NMD (nonsense-mediated mRNA decay). In order to develop an approach facilitating translation and, therefore, protection from NMD, ribosomal read-through molecules, such as aminoglycoside antibiotics, have been tested on mRNAs carrying premature stop codons. These findings have introduced new hopes for the development of a pharmacological approach to the β039 thalassemia therapy. While several strategies, designed to enhance translational read-through, have been reported to inhibit NMD efficiency concomitantly, experimental tools for systematic analysis of mammalian NMD inhibition by translational read-through are lacking. Results We developed a human cellular model of the β039 thalassemia mutation with UPF-1 suppressed and showing a partial NMD suppression. Conclusions This novel cellular model could be used for the screening of molecules exhibiting preferential read-through activity allowing a great rescue of the mutated transcripts.