Phosphorylation-dependent degradation of MEF2C contributes to regulate G2/M transition

The Myocyte Enhancer Factor 2C (MEF2C) transcription factor plays a critical role in skeletal muscle differentiation, promoting muscle-specific gene transcription. Here we report that in proliferating cells MEF2C is degraded in mitosis by the Anaphase Promoting Complex/Cyclosome (APC/C) and that this downregulation is necessary for an efficient progression of the cell cycle. We show that this mechanism of degradation requires the presence on MEF2C of a D-box (R-X-X-L) and 2 phospho-motifs, pSer98 and pSer110. Both the D-box and pSer110 motifs are encoded by the ubiquitous alternate α1 exon. These two domains mediate the interaction between MEF2C and CDC20, a co-activator of APC/C. We further report that in myoblasts, MEF2C regulates the expression of G2/M checkpoint genes (14-3-3γ, Gadd45b and p21) and the sub-cellular localization of CYCLIN B1. The importance of controlling MEF2C levels during the cell cycle is reinforced by the observation that modulation of its expression affects the proliferation rate of colon cancer cells. Our findings show that beside the well-established role as pro-myogenic transcription factor, MEF2C can also function as a regulator of cell proliferation

Design methodology of an active back-support exoskeleton with adaptable backbone-based kinematics

Abstract Manual labor is still strongly present in many industrial contexts (such as aerospace industry). Such operations commonly involve onerous tasks requiring to work in non-ergonomic conditions and to manipulate heavy parts. As a result, work-related musculoskeletal disorders are a major problem to tackle in workplace. In particular, back is one of the most affected regions. To solve such issue, many efforts have been made in the design and control of exoskeleton devices, relieving the human from the task load. Besides upper limbs and lower limbs exoskeletons, back-support exoskeletons have been also investigated, proposing both passive and active solutions. While passive solutions cannot empower the human's capabilities, common active devices are rigid, without the possibility to track the human's spine kinematics while executing the task. The here proposed paper describes a methodology to design an active back-support exoskeleton with backbone-based kinematics. On the basis of the (easily implementable) scissor hinge mechanism, a one-degree of freedom device has been designed. In particular, the resulting device allows tracking the motion of a reference vertebra, i.e., the vertebrae in the correspondence of the connection between the scissor hinge mechanism and the back of the operator. Therefore, the proposed device is capable to adapt to the human posture, guaranteeing the support while relieving the person from the task load. In addition, the proposed mechanism can be easily optimized and realized for different subjects, involving a subject-based design procedure, making possible to adapt its kinematics to track the spine motion of the specific user. A prototype of the proposed device has been 3D-printed to show the achieved kinematics. Preliminary tests for discomfort evaluation show the potential of the proposed methodology, foreseeing extensive subjects-based optimization, realization and testing of the device

Effect of Mixed Lipoic Acid, Vitamin D, Phosphatidylserine and Homotaurine to Obtain a New Formulation for Brain Ageing Prevention

By 2050, it is estimated that there will be two billion people aged 60 or over, of which 131 million are expected to be affected by dementia, while depression is expected to be the second-largest cause of disability worldwide in 2020. Preventing or delaying the onset of these disorders should therefore be a priority for public health systems. There is some evidence linking certain substances present in most common food supplements with a reduced risk of neuronal degeneration improving brain health. Recently, many compounds or extracts from natural products slowing aging and extending lifespan have been reported. The main goal of this study is to develop a new formulation that delay age-related diseases in human. For this reason, the effects of selected agents (such as lipoic acid, vitamin D3, phosphatidylserine and homotaurine) were assessed in order to find a new formulation able to slow down the physiological decay linked to brain ageing. Cell viability, radical oxygen species production, inflammatory marker along with some intracellular pathways have been evaluated. The results show that the new combination is highly effective to counteract the negative effects of oxidative stress and inflammation acting through some important brain markers involved in cell survival, enhancing viability of astrocyte

Role of Vitamin D3 and Alginates in Prevention of NSAID-Dependent Cellular Injury

About 30 million people use nonsteroidal anti-inflammatory drugs. Therefore, they have a high risk of developing gastropathic and enteropathic damages. These patients receive anti-acid treatment, but a number of clinical studies provided evidence of the ineffectiveness of proton-pump inhibitors. Vitamin D, on the other hand, appears to have high preventive and therapeutic potential. Recently, it has been introduced a product that, in addition to anti-acid properties of alginates, claims to possess gastroprotective properties deriving from vitamin D3 and from plant extractsThis study was planned to verify the effectiveness of vitamin D3 combined with alginates to prevent the damage induced in cul-tured gastric cells by diclofenac during acidic or hyperacidic exposition measuring cell viability, radical oxygen species production along with apoptotic and survival pathways.Around 30 million people consume nonsteroidal anti-inflammatory drugs (NSAID) globally every day [1] since they are widely pre-scribed because of their efficacy in the management of pain, inflammation, and fever [2]. Generally, the action mechanism of these drugs consists in the inhibition of the biosynthesis of prostaglandins, the inactivation of cyclooxygenase, and an increase in leukotrienes produc-tion [3]. Adverse events associated with NSAID, such as alterations in renal function, effects on blood pressure, hepatic injury, and plate-let inhibition, are a challenge in clinical treatment optimization [4]. However, severe gastrointestinal disorder accompanied by gastric mucosal perforation and bleeding is a major concern as well as the worst outcome of prolonged NSAID-therapy [5]: indeed, they induce gastric mucosal lesions because of their acidic properties [3]. Gastric mucosal erosions, ulceration, bleeding, and perforation, as well as an increased risk of bleeding from pre-existing peptic ulcers are major causes of gastrointestinal iatrogenic diseases [6]. The mechanism behind gastric damage involves a highly acidic gastric environment that favours the migration of nonionized lipophilic NSAID into the Findings show that this combination is more potent to counteract the negative effects of diclofenac and hyperacidic conditions than some other gastroprotective agents on epithelial gastric cells. This was confirmed by the maintenance of p53 expression at physiological level. In addition, when added before diclofenac, it can exert beneficial effects counteracting the negative effect of diclof-enac alone. These data were similar to the sample treated with pantoprazole, supporting the hypothesis that the combination could act as a gastroprotector to prevent cell loss. These results have pointed out the gastroprotective effect of the combination when compared to other commercial natural ex-tracts, this effect is obtained via antioxidant pathway, inhibiting apoptosis, enhancing cell viability and activating survival kinase

La utilidad de las Tecnologías de la Información y la Comunicación (TICs) para la prevención de la depresión

Setzenes Jornades de Foment de la Investigació (Any 2011)Los problemas de salud mental generan costes importantes, tanto desde un punto de vista personal como económico y social. La Organización Mundial de la Salud estima que los problemas de salud mental suponen entre el 3% y 4% del PNB de los estados miembros de la Unión Europea (Gabriel, 2000). Estas enfermedades se refieren, principalmente, a los trastornos del estado de ánimo y a los trastornos de ansiedad. Estos datos subrayan la importancia de desarrollar estrategias y procedimientos para ayudar a las personas que padecen depresión, y también diseñar mejores herramientas para identificar a las personas en riesgo, así como programas de prevención. Tomando todo esto en consideración, en el marco del proyecto OPTIMI (Online Predictive Tools for Intervention in Mental Illness), financiado por el VII Programa marco de la Unión Europea, hemos diseñado herramientas basadas en las nuevas Tecnologías de la Información y la Comunicación (TICs) para la detección temprana y la prevención de la depresión. La hipótesis central del proyecto OPTIMI es que existe una relación importante entre depresión, estrés, y la capacidad de afrontamiento de la persona. En OPTIMI hemos desarrollado estrategias para monitorizar el comportamiento de personas expuestas a altos niveles de estrés. Contamos con herramientas de monitorización cognitiva, fisiológica y del comportamiento (verbal y motor), utilizando sensores de tasa cardiaca, actividad, electroencefalografía, reconocimiento de la voz, etc. Se han llevado a cabo una serie de ensayos de calibración que han servido para poner a prueba estos sensores en personas de alto riesgo con el objetivo de detectar los cambios asociados al estrés, el estado de ánimo y la capacidad de afrontamiento. Estas mediciones proporcionadas por los sensores se han complementado con información proporcionada por los participantes y por el clínico. El propósito de esta comunicación es presentar el diseño seguido en los estudios de calibración y algunos datos preliminares

CONSERVATION AT THE INDIVIDUAL LEVEL: SUCCESSFUL REHABILITATION AND POST-RELEASE MONITORING OF AN ITALIAN WOLF (Canis lupus italicus) INJURED IN A CAR ACCIDENT.

This case report describes the rescue of an eight-month-old male Italian wolf (Canis lupus italicus), the victim of a car accident that caused it a pulmonary contusion, a fracture of the shaft of right femur, and a metaphyseal fracture of the left stifle. A lateral surgical approach was performed to treat the animal\u2019s multiple contusions and fractures. Afterwards the wolf was transferred to a wild animal recovery center for its rehabilitation, where it fully recovered. After 35 days in captivity the wolf was thus released into the supposed home-range of its original pack, and its movements were monitored by a GPS satellite collar. The collar worked correctly for 479 days. During that period the collar acquired a total of 1202 locations, indicating that the wolf had traveled at least 1590 km, with an average monthly distance (\ub1 SD) of 102 \ub1 40 km, exploring an overall area of about 270 km2. During the first 10 days after its release, the wolf remained in the area of its supposed native pack, whereas at about the age of 10 months the wolf began to make wide extraterritorial movements. The wolf\u2019s last localization was acquired on 13th May 2018, about 17 months after its release, at a linear distance of about 65 km from the release site. This preliminary data showed that the wolf was alive and travelled long distances after its release, and demonstrates how a multidisciplinary management approach can support the recovery and successful release into nature of a rescued wild animal belonging to a flagship species with a notable ecological role, such as the Italian wolf

Očuvanje na individualnoj razini: uspješna rehabilitacija i praćenje talijanskog vuka (Canis lupus italicus) nastradalog na prometnici nakon puštanja na slobodu

This case report describes the rescue of an eight-month-old male Italian wolf (Canis lupus italicus), the victim of a car accident that caused it a pulmonary contusion, a fracture of the shaft of right femur, and a metaphyseal fracture of the left stifle. A lateral surgical approach was performed to treat the animal’s multiple contusions and fractures. Afterwards the wolf was transferred to a wild animal recovery center for its rehabilitation, where it fully recovered. After 35 days in captivity the wolf was thus released into the supposed home-range of its original pack, and its movements were monitored by a GPS satellite collar. The collar worked correctly for 479 days. During that period the collar acquired a total of 1202 locations, indicating that the wolf had traveled at least 1590 km, with an average monthly distance (± SD) of 102 ± 40 km, exploring an overall area of about 270 km2. During the first 10 days after its release, the wolf remained in the area of its supposed native pack, whereas at about the age of 10 months the wolf began to make wide extraterritorial movements. The wolf’s last localization was acquired on 13th May 2018, about 17 months after its release, at a linear distance of about 65 km from the release site. These preliminary data showed that the wolf was alive and travelled long distances after its release, and demonstrates how a multidisciplinary management approach can support the recovery and successful release into nature of a rescued wild animal belonging to a flagship species with a notable ecological role, such as the Italian wolf.Ovaj prikaz slučaja opisuje spašavanje osmomjesečnog mužjaka talijanskog vuka (Canis lupus italicus) koji je bio žrtva naleta vozila s posljedičnim nagnječenjem pluća, prijelomom vrata desne bedrene kosti prijelomom u području metafize lijevoga koljena. Primijenjen je lateralni kirurški pristup kako bi se sanirala višestruka nagnječenja i prijelomi u životinje. Nakon toga je vuk prevezen u centar za oporavak divljih životinja gdje se potpuno oporavio. Nakon 35 dana u zatočeništvu vuk je pušten u okoliš nalik na njegov prirodni te je praćen preko GPS ogrlice. Ogrlica je ispravno radila 479 dana. Za to je vrijeme pokazala 1202 lokacije, upućujući na to da je vuk prešao 1590 km, u prosjeku mjesečno 102 ± 40 km (± SD), istražujući područje od 270 km2. Prvih 10 dana nakon oslobađanja vuk je ostao u području nalik na njegov prirodni okoliš, no u dobi od 10 mjeseci počeo je odlaziti na šire područje. Posljednja je njegova lokacija zabilježena 13. svibnja 2018., oko 17 mjeseci nakon puštanja, na zračnoj udaljenosti od oko 65 km od mjesta ispuštanja. Ovaj preliminarni podatak pokazuje da je vuk bio živ i prelazio velike udaljenosti nakon oslobađanja. Također pokazuje da multidisciplinarni pristup spašavanju može pospješiti oporavak i uspješno vraćanje u prirodu divljih životinja koje pripadaju vodećim vrstama s velikom ekološkom važnošću, kao što je talijanski vuk

Cholecalciferol (vitamin D3) has a direct protective activity against interleukin 6-induced atrophy in C2C12 myotubes

We previously determined that different vitamin D metabolites can have opposite effects on C2C12 myotubes, depending on the sites of hydroxylation or doses. Specifically, 25(OH)D3 (25VD) has an anti-atrophic activity, 1,25(OH)2D3 induces atrophy, and 24,25(OH)2D3 is anti-atrophic at low concentrations and atrophic at high concentrations. This study aimed to clarify whether cholecalciferol (VD3) too, the non-hydroxylated upstream metabolite, has a direct effect on muscle cells. Assessing the effects of VD3 treatment on mouse C2C12 skeletal muscle myotubes undergoing atrophy induced by interleukin 6 (IL6), we demonstrated that VD3 has a protective action, preserving C2C12 myotubes size, likely through promoting the differentiation and fusion of residual myoblasts and by modulating the IL6-induced autophagic flux. The lack, in C2C12 myotubes, of the hydroxylase transforming VD3 in the anti-atrophic 25VD metabolite suggests that VD3 may have a direct biological activity on the skeletal muscle. Furthermore, we found that the protective action of VD3 depended on VDR, implying that VD3 too might bind to and activate VDR. However, despite the formation of VDR-RXR heterodimers, VD3 effects do not depend on RXR activity. In conclusion, VD3, in addition to its best-known metabolites, may directly impact on skeletal muscle homeostasis

The Kepler-10 planetary system revisited by HARPS-N: A hot rocky world and a solid Neptune-mass planet

Kepler-10b was the first rocky planet detected by the Kepler satellite and con- firmed with radial velocity follow-up observations from Keck-HIRES. The mass of the planet was measured with a precision of around 30%, which was insufficient to constrain models of its internal structure and composition in detail. In addition to Kepler-10b, a second planet transiting the same star with a period of 45 days was sta- tistically validated, but the radial velocities were only good enough to set an upper limit of 20 Mearth for the mass of Kepler-10c. To improve the precision on the mass for planet b, the HARPS-N Collaboration decided to observe Kepler-10 intensively with the HARPS-N spectrograph on the Telescopio Nazionale Galileo on La Palma. In to- tal, 148 high-quality radial-velocity measurements were obtained over two observing seasons. These new data allow us to improve the precision of the mass determina- tion for Kepler-10b to 15%. With a mass of 3.33 +/- 0.49 Mearth and an updated radius of 1.47 +0.03 -0.02 Rearth, Kepler-10b has a density of 5.8 +/- 0.8 g cm-3, very close to the value -0.02 predicted by models with the same internal structure and composition as the Earth. We were also able to determine a mass for the 45-day period planet Kepler-10c, with an even better precision of 11%. With a mass of 17.2 +/- 1.9 Mearth and radius of 2.35 +0.09 -0.04 Rearth, -0.04 Kepler-10c has a density of 7.1 +/- 1.0 g cm-3. Kepler-10c appears to be the first strong evidence of a class of more massive solid planets with longer orbital periods.Comment: 44 pages, 8 figures, accepted for publication in Ap