Anti-apoptotic MCL-1 Localizes to the Mitochondrial Matrix and Couples Mitochondrial Fusion to Respiration

MCL-1, an anti-apoptotic BCL-2 family member that is essential for the survival of multiple cell lineages, is also among the most highly amplified genes in cancer. Although MCL-1 is known to oppose cell death, precisely how it functions to promote survival of normal and malignant cells is poorly understood. Here, I report that different forms of MCL-1 reside in distinct mitochondrial locations and exhibit separable functions. On the outer mitochondrial membrane, a MCL-1 isoform acts like other anti-apoptotic BCL-2 molecules to antagonize apoptosis, whereas an amino-terminally truncated isoform of MCL-1 that is imported into the mitochondrial matrix is necessary to facilitate normal mitochondrial fusion, ATP production, membrane potential, respiration, cristae ultrastructure, and maintenance of oligomeric ATP synthase. My results provide insight into how MCL-1\u27s surprisingly diverse salutary functions may control the survival of both normal and cancer cells

Evidence for a functional subdivision of Premotor Ear-Eye Field (Aera 8B)

The Supplementary EyeField (SEF) and the Frontal Eye Field (FEF) have been described as participating in gaze shift control. Recent evidence suggests, however, that other areas of the dorso medial prefrontal cortex also influence gaze shift. Herein, we haveinvestigated electrically evoked ear-and eye movements from the PremotorEar-Eye Field, or PEEF (area8B) of macaque monkeys. We stimulated PEEF during spontaneous condition (outside the task performance) and during the execution of a visual fixation task(VFT). In the first case, we functionally identified two regions within the PEEF: a core and a belt. In the core region, stimulation elicited forward ear movements; regarding the evoked eye movements, in some penetrations, stimulation elicited contraversive fixed-vectors with a mean amplitude of 5.14◦; while in other penetrations, we observed prevalently contralateral goal-directed eye movements having end-points that fell within15◦ inrespect to the primary eye position. On the contrary, in the belt region,stimulation elicited backward ear movements; regarding the eye movements, in some penetrations stimulation elicited prevalently contralateral goal-directed eye movements having end-points that fell within 15◦ in respect to the primary eye position, while in the lateral edge of the investigated region, stimulation elicited contralateral goal-directedey emovements having end-points that fell beyond 15◦in respect to the primary eye position. Stimulation during VFT either did not elicit eye movements or evoked saccades of only a few degrees. Finally, even though no head rotation movements were observed during the stimulation period, we viewed a relationship between the duration of stimulation and the neck forces exerted by the monkey’shead. We propose an updated vision of the PEEF composed of two functional regions, core and belt, which may beinvolved in integrating auditory and visual information important to the programming of gaze orienting movements

Auditory and visual systems organization in Brodmann Area 8 for gaze-shift control: where we do not see, we can hear

Hearing is especially important for most primate species as they live in habitats of dense vegetation that limits vision. Stebbins (1980) summed up the evolution of the auditory system by assuming that earliest mammals exploited nocturnal niches since they were relatively free of many of the large, diurnal, predacious reptiles. Therefore, hearing and smell were more useful at night than vision. Our vision is limited not only in the dark but also outside the visual field. In fact, if we observe the behavior of a predator like a feline, oriented toward its prey, and at the same time a sound occurs behind, we might note three principal different behaviors: the predator could maintain its gaze and ears on the prey neglecting the sound source; the predator could maintain its gaze on the prey rotating ears and then shifting its auditory attention toward the sound source; finally the predator could break its attention and orient gaze and ears toward the sound source. A similar behavior is seen in human beings during social interaction with two or more interlocutors. In humans, orienting movements are carried out by the eyes, head, and/or body operating alone or in various combinations depending on the behavioral situation. However, in non-human primates, such as macaque monkeys, head orienting movements and, more generally, gaze-shift are accompanied by ear orienting movements, which allow the shifting of auditory attention toward a sound of interest (Bon and Lucchetti, 1994, 2006; Lucchetti et al., 2008; Lanzilotto et al., 2013; Yin, 2013). Considering all these assumptions, the auditory system could have an important role to detect information even from regions of the space that the visual system cannot explore without orienting movements. In other words, where we cannot see, we can hear. Through this opinion article, we argue that Brodmann Area 8 receives information from both auditory and visual systems and organizes a transformation of these sensory signals into gaze-shift motor commands. Our hypothesis is that this sensory-motor transformation is spatially organized, from both anatomical and functional points of view. Anatomical and functional properties of the Brodmann Area 8 (consisting in Area 8A plus Area 8B) support a medio-lateral organization for both auditory and visual systems. In particular, the lateral portion, corresponding to Area 8A or Frontal Eye Field (FEF), could play a role in receiving visual and auditory information from a central part of the visual field and then in organizing gaze-shift motor commands toward it. Otherwise, the medial portion, corresponding to Area 8B or Premotor Ear-Eye Field (PEEF), could play a role in receiving principally auditory information from a peripheral region of the space and then in organizing gaze-shift motor commands toward it

Coherent excitation transport through ring-shaped networks

The coherent quantum transport of matter wave through a ring-shaped circuit attached to leads defines an iconic system in mesoscopic physics that has allowed both to explore fundamental questions in quantum science and to draw important avenues for conceiving devices of practical use. Here we study the source-to-drain transport of excitations going through a ring-network, without propagation of matter waves. We model the circuit in terms of a spin system with specific long-range interactions that are relevant for quantum technology, such as Rydberg atoms trapped in optical tweezers or ion traps. Inspired by the logic of rf- and dc-SQUIDs, we consider rings with one and two local energy offsets, or detunings. As a combination of specific phase shifts in going though the localized detunings and as a result of coherent tunneling, we demonstrate how the transport of excitations can be controlled, with a distinctive dependence on the range of interactions.Comment: Main text: 9 pages, 4 figures. Appendix: 16 pages, 10 figure

Neuronal Encoding of Self and Others' Head Rotation in the Macaque Dorsal Prefrontal Cortex.

Following gaze is a crucial skill, in primates, for understanding where and at what others are looking, and often requires head rotation. The neural basis underlying head rotation are deemed to overlap with the parieto-frontal attention/gaze-shift network. Here, we show that a set of neurons in monkey's Brodmann area 9/46dr (BA 9/46dr), which is involved in orienting processes and joint attention, becomes active during self head rotation and that the activity of these neurons cannot be accounted for by saccade-related activity (head-rotation neurons). Another set of BA 9/46dr neurons encodes head rotation performed by an observed agent facing the monkey (visually triggered neurons). Among these latter neurons, almost half exhibit the intriguing property of encoding both execution and observation of head rotation (mirror-like neurons). Finally, by means of neuronal tracing techniques, we showed that BA 9/46dr takes part into two distinct networks: a dorso/mesial network, playing a role in spatial head/gaze orientation, and a ventrolateral network, likely involved in processing social stimuli and mirroring others' head. The overall results of this study provide a new, comprehensive picture of the role of BA 9/46dr in encoding self and others' head rotation, likely playing a role in head-following behaviors

Controlled flow of excitations in a ring-shaped network of Rydberg atoms

Highly excited Rydberg atoms are a powerful platform for quantum simulation and information processing. Here, we propose atomic ring networks to study chiral currents of Rydberg excitations. The currents are controlled by a phase pattern imprinted via a Raman scheme and can persist even in the presence of dephasing. Depending on the interplay between the Rabi coupling of Rydberg states and the dipole-dipole atom interaction, the current shows markedly different features. The excitations propagate with a velocity displaying a characteristic peak in time, reflecting the chiral nature of the current. We find that the time-averaged current in a quench behaves similarly to the ground-state current. This analysis paves the way for the development of new methods to transport information in atomic networks.Comment: 6 pages main, 6 figures + appendice

Flexibility of Gender Stereotypes: Italian Study on Comparative Gender-consistent and Gender-inconsistent Information

The topic of this study is flexibility in gender stereotyping linked to attribution of toys, socio-cognitive traits, and occupations in 160 Italian children aged 6 to 12 years. We used the Gender Toys Choice, the Gender Traits Choice, and the Gender Jobs Choice, a selected set of colored cards containing masculine and feminine stimuli to assign to a male or female or both male and female silhouette (the flexible-choice technique). In order to verify the change of flexibility in gender stereotyping, we made use of four cartoon stories with male and female characters with typical or atypical traits and performing gender-consistent or gender-inconsistent activities. Results indicated that the exposure to cartoon stories with gender-inconsistent information rather than cartoon stories with gender-consistent information increased flexibility in gender stereotyping, showing age differences in favor of children aged 11-12. Implications in relation to the developmental-constructivist approach were noted

Effects of age and sex on epigenetic modification induced by an acute physical exercise

It has been observed that, after 2\u200ahours of aerobic exercise, plasma interleukin-6 (IL-6) increases whereas nuclear concentrations of enzyme DNA methyltransferase (DNMT) 3B significantly decreased in peripheral blood mononuclear cells (PBMCs), with no change observed in DNMT3A. The aim of the present study was to detect differences in these changes induced by exercise in plasma IL-6 levels as well as in PBMC nuclear concentrations of DNMT3A and DNMT3B, in relation to age and sex. Four groups were studied: 12 young men (24.8\u200a\ub1\u200a1.77 years old), 12 young women (23.8\u200a\ub1\u200a1.81 years old), 12 adult men (45.8\u200a\ub1\u200a1.82 years old), 12 adult women (mean 44.5\u200a\ub1\u200a2.07 years old). Participants had to run at 60% of maximal oxygen consumption (VO2max) for 120\u200aminutes, interspersed with sprints at 90% of VO2max for the last 30\u200aseconds of every 10\u200aminutes. About 250\u200a\u3bcL of PBMCs (1\u200a 7\u200a10 cells) were treated with 100\u200a\u3bcL of either pre-exercise plasma or post-exercise plasma and nuclear DNMT3A and DNMT3B concentrations were quantified. No change in nuclear concentration of DNMT3A following the exercise was observed. Conversely, nuclear concentrations of DNMT3B significantly decreased, with a reduction of about 78% in young men, 72% in young women, 61% in adult men, and 53% in adult women. Moreover, a strong positive correlation between the nuclear concentration of DNMT3B in PBMC following stimulation with post-exercise plasma and post-exercise plasma concentrations of IL-6 was observed in all the 4 studied groups. This study confirms that a single bout of endurance exercise is sufficient to decrease nuclear concentrations of DNMT3B and thus protein upregulation. Moreover, the epigenetic mechanisms induced by exercise apparently cause more intense changes in men than in women and that, in both of them, this effect seems to decrease with age

La distribuzione della pratica nell’apprendimento di un nuovo atto motorio in età preadolescenziale

The purpose of the present study was to evaluate if, and to what extent, in elementary school children, different methods of timing distribution of training sessions are able to significantly affect the learning of a new motor task. Almost 1,000 children, aged between 6 and 10 years, participated the  study. The children had to learn an oculo-manual coordination task, completely new to them, using different ways of practice’s distributing (concentrated or distributed).The children were divided into three groups (A, B and C) and each group was subdivided into five sub-groups, correponding to the five classes of the first grade schools. The training involved 120 total launches to be carried out in a week, distributed as follows: group A performed a training distributedover 6 consecutive days; b) group B, played a training distributed in 3 alternating days (Monday, Wednesday, Friday), group C, carried out a training distributed over 3 consecutive days (Monday, Tuesday, Wednesday). Seven days after the end of the acquisition period each group repeated a session of 20 launches, divided into blocks of 10 with 5 minutes of recovery.It has been observed that, in terms of improvement, the learning of a new task, performed using the concentrated practice, appears less advantageous than that performed with distributed practice.However, what is learned with concentrated practice seems to last longer than what is learned with distributed practice. It has also been seen that the learning speed in males is greater than in females.Scopo del presente studio è stato quello di valutare se, e in che misura, in bambini di scuola elementare, differenti modalità di distribuzione temporale delle sedute di allenamento siano in grado di incidere significativamente sull’apprendimento di un nuovo compito motorio. All’esperimento hanno preso parte quasi 1.000 bambini, di età compresa tra i 6 e i 10 anni, frequentanti le Scuole Elementari.I bambini venivano avviati all’apprendimento di un compito di coordinamento oculomanuale, del tutto nuovo per loro, utilizzando differenti modalità di distribuzione della pratica (concentrata o distribuita).I bambini sono stati suddivisi in tre gruppi (A, B e C) e ogni gruppo era suddiviso in 5 sottogruppi, da ricondurre alle cinque classi delle scuole di primo grado. L’allenamento prevedeva 120 lanci complessivi da effettuarsi in una settimana, così distribuiti: il gruppo A svolgeva un allenamento distribuito in 6 giorni consecutivi; b) il gruppo B, svolgeva un allenamento distribuito in 3 giorni alternati (lunedì, mercoledì, venerdì), il gruppo C, svolgeva un allenamento distribuito in 3 giorni consecutivi (per es., lunedì, martedì, mercoledì). Sette giorni dopo la fine del periodo di acquisizione ogni gruppo ripeteva una sessione di 20 lanci, suddivisi in blocchi da 10 con 5 minuti di recupero.Si è osservato come, in termini di miglioramento, l’apprendimento di un compito, svolto utilizzando la pratica concentrata appare meno vantaggioso rispetto a quello eseguito con pratica distribuita.Tuttavia, quello che viene appreso con la pratica concentrata sembra durare di più rispetto a ciò che viene appreso con la pratica distribuita. Si è visto, inoltre, che la velocità di apprendimento nei maschi è maggiore rispetto alle femmine