Autophagy is defective in collagen VI muscular dystrophies and its reactivation rescues myofiber degeneration

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Complementary intestinal mucosa and microbiota responses to caloric restriction

The intestine is key for nutrient absorption and for interactions between the microbiota and its host. Therefore, the intestinal response to caloric restriction (CR) is thought to be more complex than that of any other organ. Submitting mice to 25% CR during 14 days induced a polarization of duodenum mucosa cell gene expression characterised by upregulation, and downregulation of the metabolic and immune/inflammatory pathways, respectively. The HNF, PPAR, STAT, and IRF families of transcription factors, particularly the Pparα and Isgf3 genes, were identified as potentially critical players in these processes. The impact of CR on metabolic genes in intestinal mucosa was mimicked by inhibition of the mTOR pathway. Furthermore, multiple duodenum and faecal metabolites were altered in CR mice. These changes were dependent on microbiota and their magnitude corresponded to microbial density. Further experiments using mice with depleted gut bacteria and CR-specific microbiota transfer showed that the gene expression polarization observed in the mucosa of CR mice is independent of the microbiota and its metabolites. The holistic interdisciplinary approach that we applied allowed us to characterize various regulatory aspects of the host and microbiota response to CR

Low in‑hospital mortality rate in patients with COVID‑19 receiving thromboprophylaxis: data from the multicentre observational START‑COVID Register

Abstract COVID-19 infection causes respiratory pathology with severe interstitial pneumonia and extra-pulmonary complications; in particular, it may predispose to thromboembolic disease. The current guidelines recommend the use of thromboprophylaxis in patients with COVID-19, however, the optimal heparin dosage treatment is not well-established. We conducted a multicentre, Italian, retrospective, observational study on COVID-19 patients admitted to ordinary wards, to describe clinical characteristic of patients at admission, bleeding and thrombotic events occurring during hospital stay. The strategies used for thromboprophylaxis and its role on patient outcome were, also, described. 1091 patients hospitalized were included in the START-COVID-19 Register. During hospital stay, 769 (70.7%) patients were treated with antithrombotic drugs: low molecular weight heparin (the great majority enoxaparin), fondaparinux, or unfractioned heparin. These patients were more frequently affected by comorbidities, such as hypertension, atrial fibrillation, previous thromboembolism, neurological disease,and cancer with respect to patients who did not receive thromboprophylaxis. During hospital stay, 1.2% patients had a major bleeding event. All patients were treated with antithrombotic drugs; 5.4%, had venous thromboembolism [30.5% deep vein thrombosis (DVT), 66.1% pulmonary embolism (PE), and 3.4% patients had DVT + PE]. In our cohort the mortality rate was 18.3%. Heparin use was independently associated with survival in patients aged ≥ 59 years at multivariable analysis. We confirmed the high mortality rate of COVID-19 in hospitalized patients in ordinary wards. Treatment with antithrombotic drugs is significantly associated with a reduction of mortality rates especially in patients older than 59 years

Post-translational modifications control foxo3 activity during denervation.

Loss of muscle mass occurs in a variety of diseases including cancer, chronic heart failure, AIDS, diabetes, and renal failure, often aggravating pathological progression. The atrophy process is controlled by a transcriptional program that regulates the expression of a subset of genes named atrophy-related genes. The Forkhead Box O (FoxO) family of transcription factors plays a critical role in the atrophy program being sufficient and necessary for the expression of rate-limiting enzymes of ubiquitin-proteasome and autophagy-lysosome systems. Therefore, a fine regulation of FoxOs is critical to avoid excessive proteolysis and cachexia. FoxO activity can be modulated by different mechanisms including phosphorylation, acetylation, ubiquitination, and glycosylation. Here we show that FoxO3 is progressively acetylated during denervation and concomitantly atrogin-1, the bona fide FoxO3 target, is downregulated. FoxO3 interacts with the histone acetyl-transferase p300, and its acetylation causes cytosolic relocalization and degradation. Several lysine residues of FoxOs are known to be acetylated. To identify which lysines are critical for FoxO3 activity we have generated different FoxO3 mutants that either mimic or prevent lysine acetylation. We found that FoxO3 mutants that mimic acetylation show a decrease of transcriptional activity and cytosolic localization. Importantly, acetylation induces FoxO3 degradation via proteasome system. Between the different lysines, lysine 262 is critical for translocation of FoxO3. In conclusion, we provide evidence that FoxO3 activity is negatively modulated by acetylation and ubiquitination in a time-dependent and coordinated manner. This fine-tuning mechanism of FoxO3 regulation may be important to prevent excessive muscle loss and can be used as a therapeutic approach to counteract muscle wasting

Drought adaptive traits for sugar beet improvement

Sugar beet is considered a high water-consuming crop. While available water resources for agriculture consumption are declining, concerns about the potential impact of climate change on crop yield and associated production costs raise the question of the future economic sustainability of the sugar beet crop. Drought negatively affects not only yield, but also the rate of sugar extraction. In this work the importance of wild beet germplasm in future breeding programs for drought tolerance is discussed

Relazione tra azoto disponibile in profondit\ue0\ua0 e qualit\ue0\ua0 estrattiva della barbabietola da zucchero

Nelle barbabietole da zucchero (Beta vulgaris L. ssp. vulgaris) coltivate in climi caldi si riscontra frequentemente, nel corso della raccolta, una diminuzione del grado polarimetrico e della qualit\ue0 estrattiva. Dato il notevole danno economico che ne deriva, si \ue8 voluto valutare l\u2018effetto sui parametri produttivi dell\u2018azoto presente in tutto il profilo di terreno esplorato dalle radici. La concentrazione dell\u2018azoto minerale e di altre propriet\ue0 chimiche del terreno in 27 siti campionati nel periodo 2000-2003 \ue8 stata correlata con il grado polarimetrico ed altri parametri qualitativi delle barbabietole. In ogni sito, sono stati prelevati campioni di terreno per strati di 0,25 m fino a 3 m di profondit\ue0. Tra i 2 e i 3 m, sono stati rinvenuti frequentemente percentuali di sostanza organica fino al 10% e concentrazioni di azoto minerale di oltre 100 mg/kg. Significative correlazioni negative sono state rilevate tra l\u2018azoto minerale presente fra 2,5 e 3 m sia con il grado polarimetrico (r = - 0,63), sia con il coefficiente di purezza (r = - 0,72). Per evitare dannose riduzioni qualitative, si conferma l\u2018utilit\ue0 del campionamento dei terreni fino alla profondit\ue0 raggiunta dalle radici e la necessit\ue0 di analizzare le pi\uf9 importanti forme di azoto. Per lo stesso scopo, dovrebbe essere evitata o adeguatamente considerata la presenza di strati organici nel profilo esplorato dalle radici

Apparato radicale e competitivit\uc3\ua0 della barbabietola da zucchero verso le malerbe

Il controllo delle specie infestanti, senza l\u2019impiego di erbicidi di sintesi, \ue8 uno dei principali limiti alla coltivazione della barbabietola da zucchero in una agricoltura low-input e/o biologica. Lo scopo del lavoro \ue8 stato quello di identificare, in due linee di barbabietola ad alta e bassa produttivit\ue0, i complessi genici legati a tratti morfofunzionali dell\u2019apparato radicale (lunghezza radicale totale, superficie radicale e numero di apici) utili indici della capacit\ue0 competitiva della barbabietola nei confronti delle malerbe. Questi caratteri sono stati valutati in plantule di sedici giorni allevate in soluzione idroponica, mentre in campo sono stati esaminati lo sviluppo radicale e la densit\ue0 delle infestanti. La linea caratterizzata da una maggiore lunghezza, superficie radicale, numero di apici e densit\ue0 radicale lungo il profilo del terreno ha evidenziato una superiore abilit\ue0 competitiva contro le malerbe (minore densit\ue0 di infestanti) e una maggiore produttivit\ue0 anche in loro presenza. Sulla progenie F1, ottenuta dall\u2019incrocio tra le due linee caratterizzate da maggiore e minore produttivit\ue0 e che hanno mostrato rispettivamente alto e basso accrescimento radicale, \ue8 stata svolta l\u2019analisi QTL al fine di identificare marcatori genetici associati alla lunghezza radicale totale. L\u2019analisi ha evidenziato l\u2019esistenza di quattro geni maggiori responsabili della lunghezza radicale. I marcatori morfofunzionali e molecolari identificati nel presente lavoro potranno consentire di selezionare linee di barbabietola che richiedono un minore impiego di mezzi tecnici per il controllo delle malerbe e, pertanto, maggiormente adattabili a sistemi agricoli eco-compatibili o basati su metodi biologici

IN-FIELD TESTING OF A NEW INSTRUMENT FOR QUALITY-CONTROL IN MAMMOGRAPHY

Instrument for non invasive quality contro