1,354,131 research outputs found
Continuare Mies. OMA a Chicago: il McCormik tribune Campus Center, IIT (2007)
Il saggio, dedicato al progetto di Rem Koolhaas per la riqualificazione di un settore del campus IIT di Mies van der Rohe a Chicago, è parte del numero monografico della rivista "Uni.city" dedicato all'architettura per l'università
Role of TAp63 in myogenesis
La miogenesi è un processo ordinato guidato da fattori regolatori miogenici (MyoD, MyoG, MRF4) che culmina nella fusione di mioblasti in miotubi. I membri della famiglia p53 sono coinvolti nel differenziamento dei mioblasti, sebbene il ruolo delle isoforme specifiche non sia stato studiato. Precedenti esperimenti hanno indicato che TAp63isoform è l'unico membro della famiglia p53 sovra regolato durante la miogenesi in vitro, suggerendo una funzione importante per questa isoforma specifica durante tale processo. Come modelli sperimentali abbiamo usato linee cellulari di mioblasti murini stabili modificate C2C7 e C2C12 (shp63 C2C7 e TAp63 C2C12 inducibile da doxiciclina). L'analisi “microarray” delle cellule C2C7 shp63 rispetto al controllo ha rivelato cambiamenti nell'espressione dei geni che codificano per le proteine coinvolte nei processi cellulari di proliferazione e metabolici. Abbiamo confermato che i cloni shp63 hanno un aumento del loro potenziale proliferativo, valutato mediante dosaggio di clonogenicità e saggio di incorporazione di EdU, ed un ritardo nel differenziamento, valutato mediante l'analisi WB di specifici marcatori di differenziamento. Le stesse analisi hanno dimostrato che la sovra espressione di TAp63 è in grado di diminuire la proliferazione cellulare. Inoltre, abbiamo osservato un aumento della produzione di ROS mitocondriali valutato mediante tecniche citofluorimetriche ed una diminuzione del consumo di ossigeno, rilevata dall’analisi “seahorse”. Il sequenziamento dell'RNA ed il sequenziamento della ChIP per la modificazione dell'istone H3K27ac, eseguita durante il differenziamento della linea C2C7, alla quale ha seguito l’a analisi “microarray” in cellule shp63 ha rivelato anche diversi geni (codificanti e non codificanti) modulati durante il differenziamento dei mioblasti in vitro. Tra questi, abbiamo trovato Igf2. Igf2 è coinvolto nello sviluppo e nel differenziamento muscolare, sia in vivo che in vitro. Abbiamo scoperto che p63 lega le sue regioni enhancer, indicando il suo coinvolgimento nella regolazione dell'espressione di Ifg2 durante il differenziamento. È interessante notare che il “long nonj coding RNA” Airn, è sotto-regolato in assenza di p63 durante il differenziamento ed il suo silenziamento ha portato ad una diminuzione nell livello di mRNA e della proteina dei marcatori di differenziamento miogenici (MyoD e MyoG). Inoltre, con il saggio dell'attività luciferasica, abbiamo scoperto che p63 regola direttamente l'espressione di Airn, legando specifici potenziatori. In sintesi, i nostri dati rivelano un nuovo ruolo per TAp63 nel controllo della proliferazione di mioblasti, del metabolismo energetico e anche del differenziamento attraverso l'espressione di specifici geni codificanti per proteine bersaglio e geni non codificanti. Le osservazioni preliminari, utilizzando set di dati pubblici disponibili, hanno confermato che l'isoforma TAp63 è tra i membri della famiglia p53 la più espressa nel muscolo scheletrico sano umano adulto. È interessante notare che un profilo genico dell'intero genoma del muscolo scheletrico dei pazienti con distrofia muscolare (DMD) di Duchenne precoce, ha mostrato una significativa riduzione dell'espressione dell'isoforma TAp63 nei tessuti interessati. Quest'ultima osservazione indica un nuovo possibile scenario futuro per lo studio del contributo di TAp63 alle patologie degenerative muscolari.Myogenesis is an ordered process driven by myogenic regulatory factors (MyoD, MyoG, MRF4) culminating in the fusion of myoblasts in myotubes. p53 family members are involved in myoblasts differentiation, although the role of the specific isoforms has not been investigated. Previous experiments indicated that TAp63γ isoform is the only member of the p53 family up-regulated during in vitro myogenesis, suggesting an important function for this specific isoform during this process. As experimental models we used stable modified murine myoblasts cell lines C2C7 and C2C12 (shp63 C2C7 and doxycycline-inducible TAp63γ C2C12). Microarray analysis of shp63 C2C7 cells compared to control revealed changes in the expression of genes which codify for proteins involved in cellular proliferation and metabolic processes. We confirmed that shp63 clones had an increase in their proliferative potential, evaluated by clonogenicity assay and EdU incorporation assay, and a delay in differentiation, evaluated by WB analysis of specific differentiation markers. The same assays showed that TAp63γ overexpression is able to decrease cell proliferation. Moreover, we observed an increase in mitochondrial ROS production evaluated by citofluorimetric techniques and a decrease in oxygen consumption, revealed by Seahorse analyser. RNA sequencing and ChIP sequencing for histone modification H3K27ac, performed during C2C7 differentiation, followed by microarray analysis carried out in shp63 cells revealed also several genes (coding and non coding) modulated during in vitro myoblast differentiation. Among them, we found Igf2. Igf2 is involved in muscle development and differentiation, both in vivo and in vitro. We found that p63 binds its enhancer regions, indicating its involvement in regulating Ifg2 expression during differentiation. Interestingly, we found that the long non coding RNA, Airn, is down-regulated in absence of p63 during differentiation and its silencing led to a decrease in either mRNA and protein level of myogenic differentiation markers (MyoD and MyoG). Moreover, by luciferase activity assay, we found that p63 regulates Airn expression directly, binding specific enhancers. In summary, our data reveal a novel role for TAp63 in controlling myoblasts proliferation, energy metabolism and also differentiation through the expression of specific target protein coding genes and long non coding genes. Preliminary observations, using publicity available datasets, confirmed that TAp63 isoform is among the p53-family members the isoform more expressed in adult human normal skeletal muscle. Interestingly, a genome-wide gene expression profiling of skeletal muscle from early Duchenne muscular dystrophy (DMD) patients showed a significant reduction of the TAp63 isoform expression in the affected tissues. The latter observation indicate new possible scenario for studying TAp63 contribution to muscle degenerative pathologies
Low-energy phenomenology of scalarless standard-model extensions with high-energy Lorentz violation
We consider renormalizable standard model extensions that violate Lorentz symmetry at high energies, but preserve CPT, and do not contain elementary scalar fields. A Nambu-Jona-Lasinio mechanism gives masses to fermions and gauge bosons and generates composite Higgs fields at low energies. We study the effective potential at the leading order of the large-N(c) expansion, prove that there exists a broken phase, and study the phase space. In general, the minimum may break invariance under boosts, rotations, and CPT, but we give evidence that there exists a Lorentz invariant phase. We study the spectrum of composite bosons and the low-energy theory in the Lorentz phase. Our approach predicts relations among the parameters of the low-energy theory. We find that such relations are compatible with the experimental data within theoretical errors. We also study the mixing among generations, the emergence of the CKM matrix, and neutrino oscillations
Renormalization of high-energy Lorentz-violating four-fermion models
We study the one-loop renormalization of high-energy Lorentz-violating four-fermion models. We derive general formulas and then consider a number of specific models. We study the conditions for asymptotic freedom and give a practical method to determine the asymptotic-freedom domain. We also point out that in some models the renormalization-group flow contains rational Zimmermann trajectories that might hide new symmetries
Efficacy and tolerability of pregabalin as preventive treatment for migraine: a 3-month follow-up study
Motor reinnervation during muscular activity
Motor reinnervation during muscular activity
Sartini S, Bartolini F, Lattanzi D, Ciuffoli S, Ambrogini P, Cuppini R
Dept. Human, Environmental, Natural Scieces, University of Urbino “Carlo Bo”, Italy.
Following nerve injury and regeneration, a transient phase of multiple innervation of muscle cells occurs. Successively, 1:1 ratio of innervation is progressively reached. Two mechanisms has been proposed to explain these processes: nerve-terminal competition for muscle released growth factors and the different pattern of axon activity. We showed running to enhance muscle expression of BDNF, a trophic factor inducing sprouting. Thus we investigated the role of running early in post-traumatic reinnervation.
We used intracellular recordings and miography to evaluate the reinnervation of soleus muscle following nerve crush, in running and sedentary rats.
In sedentary rats, about 10% of recorded muscle cells was found to be multiply innervated from 7 to 45 days from nerve crush. In runners, multiple innervation reached 34% 10 days after nerve crush and this percentage gradually decreased during the following days, although it remained significantly higher with respect to sedentary group. This effect of running was reversible.
Both in runner and sedentary rats all axons were showed to be regenerated 10 days after nerve crush, but in runners recovery of muscle strength was higher and muscle reinnervation was almost complete.
On the basis of present results, we hypothesize that intense motoneuron-muscle activity might induce up-regulation of one or more neurotrophic factors released by muscle cells, that might induce motor nerve terminal sprouting and consequent massive muscle cell multiple innervation. This model allow to link nerve-terminal competition and axon activity hypotheses and is intriguing considering the importance of physical activity during rehabilitation and the correlated exercise protocol planning
Triage body temperature predicts outcome in cats at emergency department admission: a retrospective study of 1440 cases (January 2018 to December 2021)
OBJECTIVES: The aim of the study was to evaluate the association between triage body temperature (BT) and outcome in cats presenting to the emergency department (ED). METHODS: A retrospective observational study was conducted on cats presented to the ED. BT, clinical diagnosis and outcome were recorded. BT was categorised as follows: normothermia (37.8-39.7°C); hyperthermia (⩾39.8°C); mild hypothermia (36.8-37.7°C); moderate hypothermia (35.6-36.7°C); severe hypothermia (33.1-35.5°C); and critical hypothermia (⩽33°C). Outcome in the ED was categorised as death, euthanasia, hospital admission and discharge. Outcome at hospital discharge was evaluated in patients admitted to the intensive care unit (ICU). Systemic inflammatory response syndrome (SIRS) was identified in patients. No-SIRS cats were divided into three disease categories (urinary system, cardiovascular and miscellanea) and SIRS cats into four categories (urinary system, cardiovascular, trauma and miscellanea). The presence of sepsis was evaluated. Non-parametric statistics were used. RESULTS: A total of 1440 cats were included. The hospital mortality rate was 21.9%. Hypothermia in the ED was reported in 510 (35.4%) cats, normothermia in 849 (59%) cats and hyperthermia in 81 (5.6%) cats. In the ED, the median temperature in non-survivors (35.4°C, 95% confidence interval [CI] 34.6-36.3) was significantly lower than in survivors (38.2°C, 95% CI 38.1-38.3; P <0.0001). The risk of non-survival in the ED was significantly higher in cats with a decreased BT, progressively increasing with the severity of hypothermia (P <0.0001). Furthermore, BT was significantly associated with a higher risk of mortality in the ICU (P <0.0001). A diagnosis of sepsis was associated with a high prevalence of hypothermia (79/124 cats, 63.7%) and a higher risk of non-survival (odds ratio [OR] 2.62, 95% CI 1.52-4.54; P = 0.0006). The mortality risk significantly increased in SIRS cats with a cardiovascular disease (OR 8.27, 95% CI 4.09-16.68; P <0.0001). CONCLUSIONS AND RELEVANCE: Hypothermia is common in cats at ED admission and is significantly associated with outcome. Triage hypothermia might identify patients with sepsis or SIRS complicated by comorbidities, such as cardiovascular and urinary diseases
IL BRAND
Negli anni 70 in Italia si sviluppa la moda per un pubblico di massa, un settore che proprio a partire da quegli anni vive un'accelerazione straordinaria a livello nazionale, realizzando inaspettatamente un fenomeno industriale che diventerà primario nell'economia del paese. In questo settore in cui la creatività, la sensibilità artistica, ma anche l'intuito e la competitività commerciale sono fondamentali, Piero Guidi e tutti gli altri come lui, che vengono dalla bella provincia italiana, portano il patrimonio di creatività, sensibilità e conoscenze, ma soprattutto la voglia di emergere e la sfrontatezza, fino al limite dell'azzardo nell'affrontare il mare aperto. Per fare ciò una molla straordinaria è il desiderio e la volontà di uscire dall'orizzonte bloccato in cui sono nati per raggiungere gli spazi compressi delle grandi città in cui si celebrano con inaudito clamore assieme ai fasti del consumo, quelli del cambiamento e si muovevano i fili di un mercato che comincia ad essere internazionale
Myoblasts rely on TAp63 to control basal mitochondria respiration
p53, with its family members p63 and p73, have been shown to promote myoblast differentiation by regulation of the function of the retinoblastoma protein and by direct activation of p21(Cip)(/)(Waf1) and p57(Kip2), promoting cell cycle exit. In previous studies, we have demonstrated that the TAp63 gamma isoform is the only member of the p53 family that accumulates during in vitro myoblasts differentiation, and that its silencing led to delay in myotube fusion. To better dissect the role of TAp63 gamma in myoblast physiology, we have generated both sh-p63 and Tet-On inducible TAp63 gamma clones. Gene array analysis of sh-p63 C2C7 clones showed a significant modulation of genes involved in proliferation and cellular metabolism. Indeed, we found that sh-p63 C2C7 myoblasts present a higher proliferation rate and that, conversely, TAp63 gamma ectopic expression decreases myoblasts proliferation, indicating that TAp63 gamma specifically contributes to myoblasts proliferation, independently of p53 and p73. In addition, sh-p63 cells have a defect in mitochondria respiration highlighted by a reduction in spare respiratory capacity and a decrease in complex I, IV protein levels. These results demonstrated that, beside contributing to cell cycle exit, TAp63 gamma participates to myoblasts metabolism control
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