Mitochondrial energetics in liver and skeletal muscle after energy restriction in young rats.

The present study investigated the effect of 2 weeks of energy restriction on whole body, liver and skeletal muscle energy handling. We measured whole-body oxygen consumption, as well as mitochondrial protein mass, respiratory capacity and energetic coupling in liver and skeletal muscle from food-restricted (FR) rats, age- and weight-matched controls. We also assessed markers of oxidative damage and antioxidant defences. The present results show that, in response to energy restriction, an adaptive decrease in whole-body energy expenditure is coupled with structural and functional changes in mitochondrial compartment, both in liver and skeletal muscle. In fact, liver mitochondrial mass per g of liver significantly increased, whereas total hepatic mitochondrial oxidative capacity was lower in FR than in control rats, because of a significant decrease in liver contribution to total body weight. In skeletal muscle, sub-sarcolemmal (SS) mitochondrial respiratory capacity, as well as SS and inter-myofibrillar (IMF) mitochondrial protein mass per g of tissue, was significantly lower in FR rats, compared to controls. Finally, a decrease in oxidative damage was found in liver but not in skeletal muscle mitochondria from FR rats, whereas an increase in antioxidant defence was found in both tissues. From the present results, it appears that skeletal muscle is involved in the decrease in energy expenditure induced by energy restriction. Energy sparing is achieved through changes in the activity (SS), mass (SS and IMF) and efficiency (IMF) of mitochondrial compartment.</jats:p

Mitochondrial energetics in liver and skeletal muscle after energy restriction in young rats

The present study investigated the effect of 2 weeks of energy restriction on whole body, liver and skeletal muscle energy handling. We measured whole-body oxygen consumption, as well as mitochondrial protein mass, respiratory capacity and energetic coupling in liver and skeletal muscle from food-restricted (FR) rats, age- and weight-matched controls. We also assessed markers of oxidative damage and antioxidant defences. The present results show that, in response to energy restriction, an adaptive decrease in whole-body energy expenditure is coupled with structural and functional changes in mitochondrial compartment, both in liver and skeletal muscle. In fact, liver mitochondrial mass per g of liver significantly increased, whereas total hepatic mitochondrial oxidative capacity was lower in FR than in control rats, because of a significant decrease in liver contribution to total body weight. In skeletal muscle, sub-sarcolemmal (SS) mitochondrial respiratory capacity, as well as SS and inter-myofibrillar (IMF) mitochondrial protein mass per g of tissue, was significantly lower in FR rats, compared to controls. Finally, a decrease in oxidative damage was found in liver but not in skeletal muscle mitochondria from FR rats, whereas an increase in antioxidant defence was found in both tissues. From the present results, it appears that skeletal muscle is involved in the decrease in energy expenditure induced by energy restriction. Energy sparing is achieved through changes in the activity (SS), mass (SS and IMF) and efficiency (IMF) of mitochondrial compartmen

Piconewton Mechanical Forces Promote Neurite Growth

Investigations over half a century have indicated that mechanical forces induce neurite growth, with neurites elongating at a rate of 0.1–0.3 μm h−1 pN−1 when mechanical force exceeds a threshold, with this being identified as 400–1000 pN for neurites of PC12 cells. In this article, we demonstrate that neurite elongation of PC12 cells proceeds at the same previously identified rate on application of mechanical tension of ∼1 pN, which is significantly lower than the force generated in vivo by axons and growth cones. This observation raises the possibility that mechanical tension may act as an endogenous signal used by neurons for promoting neurite elongation

Costruire l’identità della nazione italiana attraverso la danza: Carlo Blasis e le sue «storie del ballo» (1870-1878)

Après l’Unification italienne, le chorégraphe et théoricien Carlo Blasis publia deux textes, Histoire de la danse à partir des Etrusques et jusqu’aux temps récents (1870-1878), et Histoire de la danse et de son action simultanée avec la musique, la poésie, la sculpture, la peinture et les beaux-arts (1871-1878). Les deux textes, incomplets et longtemps oubliés, ont été récemment découverts et montrent la façon où le chorégraphe prit part au procès de construction de l’identité italienne. Quel usage fit-il du répertoire des concepts et des thématiques qui caractérisait le récit que l’on faisait à ce temps sur l’histoire de la danse et des usages appartenant aux diverses populations qui avaient vécu en Italie ? Quel rôle jouèrent les représentations façonnées par le mouvement du Risorgimento dans la terminologie qu’il adopta, dans les métaphores et les symboles qu’il utilisa ? Dans ses deux « Histoires de la Danse » les argumentations et les thématiques interagissent et se renforcent réciproquement. L’analyse de ces textes montre la façon où un chorégraphe se fit un patriote : en syntonie avec plusieurs intellectuels de son époque, il fit de son mieux pour contribuer à « régénérer » la danse, les arts et la science, et pour démontrer l’existence de ce « génie italien » que l’on croyait perdu.After the Italian Unification (1861), the Italian dance theoretician and choreographer Carlo Blasis published two texts in periodicals, Storia del ballo in Italia dagli Etruschi sino all’epoca recente (1870-1878), and Storia del ballo e loro azione simultanea con la musica, la poesia, la scultura, la pittura e le altre arti belle (1871-1878). Both texts, unfinished and long forgotten, have recently come to light. They show the way how this choreographer took part to the process of construction of the Italian national identity. How did Blasis use the repertory of concepts and themes which were part of the way how the history of the dance and the habits belonging to the several populations which had lived in Italy, was narrated in his time? What role did the canonical representations shaped by the so-called Risorgimento movement play in the terminology he adopted, in the metaphors and symbols he shaped? In his two «Dance Histories» themes and arguments interact, and strengthen one another. Blasis shows the way how a choreographer became a patriot: in tune with other intellectuals of his time, he did his best to «regenerate» dance, arts and science, and contributed to assert the existence of the Italian «genius» which was reputed forever lost.La recente scoperta di due saggi incompleti e dimenticati del trattatista e coreografo italiano Carlo Blasis, Storia del ballo in Italia dagli Etruschi sino all’epoca recente (1870-1878), e la Storia del ballo e loro azione simultanea con la musica, la poesia, la scultura, la pittura e le altre arti belle (1871-1878), ambedue usciti su periodici dopo l’Unificazione italiana (1870), consente di indagare sul modo in cui il grande teorico si è adoperato alla costruzione dell’identità nazionale. Come usò Blasis in quei testi il repertorio di concetti e di tematiche che appartenevano alla storia della danza così come era narrata a quei tempi, ed anche alla storia degli usi e dei costumi dei popoli vissuti sul suolo italico? Nella terminologia, nella simbologia e nelle metafore che adottò, che ruolo giocarono le rappresentazioni che facevano parte del canone risorgimentale di costruzione della nazione? Nelle sue due «Storie del ballo», gli argomenti interagiscono, facendo da reciproca cassa di risonanza. Così Blasis dimostra il modo in cui un coreografo può diventare patriota: in sintonia con altri intellettuali del suo tempo, egli si adoperò per la «rigenerazione» della danza, delle arti e delle scienze, contribuendo a rivendicare i lumi di quel «genio italico» che si credevano perduti

Dysregulation of microRNA biogenesis in cancer: the impact of mutant p53 on Drosha complex activity

A widespread decrease of mature microRNAs is often observed in human malignancies giving them potential to act as tumor suppressors. Thus, microRNAs may be potential targets for cancer therapy. The global miRNA deregulation is often the result of defects in the miRNA biogenesis pathway, such as genomic mutation or aberrant expression/localization of enzymes and cofactors responsible of miRNA maturation. Alterations in the miRNA biogenesis machinery impact on the establishment and development of cancer programs. Accumulation of pri-microRNAs and corresponding depletion of mature microRNAs occurs in human cancers compared to normal tissues, strongly indicating an impairment of crucial steps in microRNA biogenesis. In agreement, inhibition of microRNA biogenesis, by depletion of Dicer1 and Drosha, tends to enhance tumorigenesis in vivo. The p53 tumor suppressor gene, TP53, is mutated in half of human tumors resulting in an oncogene with Gain-Of-Function activities. In this review we discuss recent studies that have underlined a role of mutant p53 (mutp53) on the global regulation of miRNA biogenesis in cancer. In particular we describe how a new transcriptionally independent function of mutant p53 in miRNA maturation, through a mechanism by which this oncogene is able to interfere with the Drosha processing machinery, generally inhibits miRNA processing in cancer and consequently impacts on carcinogenesis

Triplet vs doublet lenalidomide-containing regimens for the treatment of elderly patients with newly diagnosed multiple myeloma

Lenalidomide-dexamethasone improved outcome in newly diagnosed elderly multiple myeloma patients. We randomly assigned 662 patients who were age \u202165 years or transplantation-ineligible to receive induction with melphalan-prednisone-lenalidomide (MPR) or cyclophosphamide-prednisone-lenalidomide (CPR) or lenalidomide plus lowdose dexamethasone (Rd). The primary end point was progression-free survival (PFS) in triplet (MPR and CPR) vs doublet (Rd) lenalidomide-containing regimens. After a median follow-up of 39 months, the medianPFSwas22 months for the triplet combinations and 21 months for the doublet (P 5 .284). The median overall survival (OS) was not reached in either arms, and the 4-year OS was 67% for the triplet and 58% for the doublet arms (P 5 .709). By considering the 3 treatment arms separately, no difference in outcome was detected among MPR, CPR, and Rd. The most common grade \u20213 toxicity was neutropenia: 64% in MPR, 29% in CPR, and 25% in Rd patients (P < .0001). Grade \u20213 nonhematologic toxicities were similar among arms and were mainly infections (6.5% to 11%), constitutional (3.5% to 9.5%), and cardiac (4.5% to 6%), with no difference among the arms. In conclusion, in the overall population, the alkylator-containing tripletsMPRandCPRwere not superior to the alkylator-free doublet Rd, which was associated with lower toxicit

Flaring Behavior of the Quasar 3C~454.3 across the Electromagnetic Spectrum

We analyze the behavior of the parsec-scale jet of the quasar 3C~454.3 during pronounced flaring activity in 2005-2008. Three major disturbances propagated down the jet along different trajectories with Lorentz factors $\Gamma>$10. The disturbances show a clear connection with millimeter-wave outbursts, in 2005 May/June, 2007 July, and 2007 December. High-amplitude optical events in the $R$-band light curve precede peaks of the millimeter-wave outbursts by 15-50 days. Each optical outburst is accompanied by an increase in X-ray activity. We associate the optical outbursts with propagation of the superluminal knots and derive the location of sites of energy dissipation in the form of radiation. The most prominent and long-lasting of these, in 2005 May, occurred closer to the black hole, while the outbursts with a shorter duration in 2005 Autumn and in 2007 might be connected with the passage of a disturbance through the millimeter-wave core of the jet. The optical outbursts, which coincide with the passage of superluminal radio knots through the core, are accompanied by systematic rotation of the position angle of optical linear polarization. Such rotation appears to be a common feature during the early stages of flares in blazars. We find correlations between optical variations and those at X-ray and $\gamma$-ray energies. We conclude that the emergence of a superluminal knot from the core yields a series of optical and high-energy outbursts, and that the mm-wave core lies at the end of the jet's acceleration and collimation zone.Comment: 57 pages, 23 figures, 8 tables (submitted to ApJ

Risk adjusted mortality after hip replacement surgery. A retrospective study

Introduction: Hip replacement (HR) operations are increasing. Short term mortality is an indicator of quality; few studies include risk adjustment models to predict HR outcomes. We evaluated in-hospital and 30-day mortality in hospitalized patients for HR and compared the performance of two risk adjustment algorithms. Materials and methods: A retrospective cohort study on hospital discharge records of patients undergoing HR from 2000 to 2005 in Tuscany Region, Italy, applied All-Patient Refined Diagnosis Related Groups (APR-DRG) and Elixhauser Index (EI) risk adjustment models to predict outcomes. Logistic regression was used to analyse the performance of the two models; C statistic (C) was used to define their discriminating ability. Results: 25,850 hospital discharge records were studied. In-hospital and 30-day crude mortality were 1.3% and 3%, respectively. Female gender was a significant (p&lt;0.001) protective factor under both models and had the following Odds Ratios (OR):  0.64 for in-hospital and 0.51 for 30-day mortality using APR-DRG and 0.55 and 0.48, respectively, with EI. Among EI comorbidities, heart failure and liver disease were associated with in-hospital (OR 9.29 and 5.60; p&lt;0.001) and 30-day (OR 6.36 and 3.26; p&lt;0.001) mortality. Increasing age and APR-DRG risk class were predictive of all the outcomes. Discriminating ability for in-hospital and 30-day mortality was reasonable with EI (C 0.79 and 0.68) and good with APR-DRG (C 0.86 and 0.82). Conclusions: Our study found that gender, age, EI comorbidities and APR-DRG risk of death are predictive factors of in-hospital and 30-day mortality outcomes in patients undergoing HR. At least one risk adjustment algorithm should always be implemented in patient management