Characterization of the DNA-unwinding activity of human RECQ1, a helicase specifically stimulated by human replication protein A.

The RecQ helicases are involved in several aspects of DNA metabolism. Five members of the RecQ family have been found in humans, but only two of them have been carefully characterized, BLM and WRN. In this work, we describe the enzymatic characterization of RECQ1. The helicase has 3' to 5' polarity, cannot start the unwinding from a blunt-ended terminus, and needs a 3'-single-stranded DNA tail longer than 10 nucleotides to open the substrate. However, it was also able to unwind a blunt-ended duplex DNA with a "bubble" of 25 nucleotides in the middle, as previously observed for WRN and BLM. We show that only short DNA duplexes (30 bp) can be unwound by RECQ1 alone, but the addition of human replication protein A (hRPA) increases the processivity of the enzyme (100 bp). Our studies done with Escherichia coli single-strand binding protein (SSB) indicate that the helicase activity of RECQ1 is specifically stimulated by hRPA. This finding suggests that RECQ1 and hRPA may interact also in vivo and function together in DNA metabolism. Comparison of the present results with previous studies on WRN and BLM provides novel insight into the role of the N- and C-terminal domains of these helicases in determining their substrate specificity and in their interaction with hRPA

Sex Differences in Cardiovascular Diseases: A Matter of Estrogens, Ceramides, and Sphingosine 1-Phosphate

The medical community recognizes sex-related differences in pathophysiology and cardiovascular disease outcomes (CVD), culminating with heart failure. In general, pre-menopausal women tend to have a better prognosis than men. Explaining why this occurs is not a simple matter. For decades, sex hormones like estrogens (Es) have been identified as one of the leading factors driving these sex differences. Indeed, Es seem protective in women as their decline, during and after menopause, coincides with an increased CV risk and HF development. However, clinical trials demonstrated that E replacement in post-menopause women results in adverse cardiac events and increased risk of breast cancer. Thus, a deeper understanding of E-related mechanisms is needed to provide a vital gateway toward better CVD prevention and treatment in women. Of note, sphingolipids (SLs) and their metabolism are strictly related to E activities. Among the SLs, ceramide and sphingosine 1-phosphate play essential roles in mammalian physiology, particularly in the CV system, and appear differently modulated in males and females. In keeping with this view, here we explore the most recent experimental and clinical observations about the role of E and SL metabolism, emphasizing how these factors impact the CV system

Role of iron and ferritin in TNFα-induced apoptosis in HeLa cells

AbstractWe found that tumor necrosis factor α (TNFα)-induced apoptosis in HeLa cells was accompanied by a ∼2-fold increase in H- and L-ferritin and a decrease in transferrin receptor, two indices of increased iron availability. Iron supplementation and overexpression of H-ferritin or its mutant with an inactivated ferroxidase center reduced by about ∼50% the number of apoptotic cells after TNFα-treatment, while overexpression of L-ferritin was ineffective. The data indicate that H-ferritin has an anti-apoptotic activity unrelated to its ferroxidase activity and to its capacity to modify cellular iron metabolism

Environmental impacts of using desalinated water in concrete production in areas affected by freshwater scarcity

Up to 500 litres of water may be consumed at the batching plant per cubic meter of ready mix concrete, if water for washing mixing trucks and equipment is included. Demand for concrete is growing almost everywhere, regardless of local availability of freshwater. The use of freshwater for concrete production exacerbates stress on natural water resources. In water-stressed coastal countries such as Israel, desalinated seawater (DSW) is often used in the production of concrete. However, the environmental impacts of this practice have not yet been assessed. In this study the effect of using DSW on the water and carbon footprints of concrete was investigated using life cycle assessment. Water footprint results highlight the benefits of using DSW rather than freshwater to produce concrete in Israel. In contrast, because desalination is an energy intensive process, using DSW increases the greenhouse gas intensity of concrete. Nevertheless, this increase (0.27 kg CO2e/m3 concrete) is small, if compared to the life cycle greenhouse gas emissions of concrete. Our results show that using untreated seawater in the mix (transported by truck from the coast) in place of DSW, would be beneficial in terms of water and carbon footprints if the batching plant were located less than 13 km from the withdrawal point. However, use of untreated seawater increases steel reinforcement corrosion, resulting in loss of structural integrity of the reinforced concrete composite. Sustainability of replacing steel with non-corrosive materials should be explored as a way to reduce both water and carbon footprints of concrete

Human Mitochondrial Ferritin Expressed in HeLa Cells Incorporates Iron and Affects Cellular Iron Metabolism

Mitochondrial ferritin (MtF) is a newly identified ferritin encoded by an intronless gene on chromosome 5q23.1. The mature recombinant MtF has a ferroxidase center and binds iron in vitro similarly to H-ferritin. To explore the structural and functional aspects of MtF, we expressed the following forms in HeLa cells: the MtF precursor (approximately 28 kDa), a mutant MtF precursor with a mutated ferroxidase center, a truncated MtF lacking the approximately 6-kDa mitochondrial leader sequence, and a chimeric H-ferritin with this leader sequence. The experiments show that all constructs with the leader sequence were processed into approximately 22-kDa subunits that assembled into multimeric shells electrophoretically distinct from the cytosolic ferritins. Mature MtF was found in the matrix of mitochondria, where it is a homopolymer. The wild type MtF and the mitochondrially targeted H-ferritin both incorporated the (55)Fe label in vivo. The mutant MtF with an inactivated ferroxidase center did not take up iron, nor did the truncated MtF expressed transiently in cytoplasm. Increased levels of MtF both in transient and in stable transfectants resulted in a greater retention of iron as MtF in mitochondria, a decrease in the levels of cytosolic ferritins, and up-regulation of transferrin receptor. Neither effect occurred with the mutant MtF with the inactivated ferroxidase center. Our results indicate that exogenous iron is as available to mitochondrial ferritin as it is to cytosolic ferritins and that the level of MtF expression may have profound consequences for cellular iron homeostasis

Neurocognitive Impairment in HIV-Infected Naïve Patients with Advanced Disease: The Role of Virus and Intrathecal Immune Activation

Objective. To investigate intrathecal immune activation parameters and HIV-RNA in HIV-associated neurocognitive disorders (HAND) of advanced naïve HIV-infected patients and to evaluate their dynamics before and after initiation of antiretroviral therapy (ART). Methods. Cross-sectional and longitudinal analysis of HIV RNA, proinflammatory cytokines (IL-6, IL-10, INF-γ, TNF-α, TGF-β1, and TGF-β2) and chemokines (MIP-1α, MIP-1β, and MCP-1) in plasma and cerebrospinal fluid (CSF) of HIV-infected patients with CD4 <200/μL. Results. HAND was diagnosed at baseline in 6/12 patients. Baseline CSF HIV-RNA was comparable in patients with or without HAND, whereas CSF concentration of IL-6 and MIP-1β, proinflammatory cytokines, was increased in HAND patients. CSF evaluation at 12 weeks was available in 10/12 cases. ART greatly reduced HIV-RNA in all patients. Nevertheless, IL-6 and MIP-1β remained elevated after 12 weeks of therapy in HAND patients, in whom CSF HIV RNA decay was slower than the plasmatic one as well. Conclusion. Immune activation, as indicated by inflammatory cytokines, but not higher levels of HIV-RNA is observed in advanced naïve HIV-infected patients with HAND. In HAND patients, ART introduction resulted in a less rapid clearance of CSF viremia compared to plasma and no modifications of intratechal immune activation

Restituire un museo alla cittadinanza. Il caso del MusAB

Nato nel 2015 come museo dell’Istituto Nazionale di Astrofisica e riconosciuto dalla Regione Lombardia come collezione museale, il Museo Astronomico di Brera (MusAB) è una straordinaria collezione di strumenti utilizzati dal personale dell’Osservatorio astronomico di Brera nel corso di 250 anni di storia. Oggi, grazie a un finanziamento della Regione Lombardia, nell’ambito di un’iniziativa volta al miglioramento dei luoghi della cultura, il MusAB ha l’ambizione di rispondere alla domanda: cosa fa l’astronomo/a? Osservare, scoprire, misurare, rappresentare, sono le operazioni che caratterizzano il loro lavoro e che la nuova esposizione cerca di illustrare con l’aiuto degli antichi strumenti della Specola di Brera. La realizzazione di questo nuovo allestimento ha coinvolto diverse figure professionali che hanno trovato soluzioni per raccontare difficili argomenti scientifici al grande pubblico, attraverso i testi discorsivi, una nuova distribuzione nello spazio degli strumenti e immagini evocative. La comunicazione del progetto ha sfruttato i canali dell’Osservatorio, valorizzando la nuova identità visiva del museo e il portale web. In attesa della riapertura sono stati realizzati materiali divulgativi e multimediali con studenti delle scuole superiori e stagisti in master in divulgazione della scienza. Il museo ha inaugurato il nuovo allestimento il 5 marzo 2021, in occasione di Milano MuseoCity in diretta sul canale YouTube dell’INAF-Osservatorio Astronomico di Brera, ma ha riaperto ufficialmente, a causa dell’emergenza pandemica, solamente il 7 dicembre 2021. Nella parte finale di questo documento analizziamo l’impatto sul pubblico di questo progetto attraverso i dati raccolti in questa prima giornata di apertura

Is Delirium the Cognitive Harbinger of Frailty in Older Adults? A Review about the Existing Evidence

Frailty is a clinical syndrome defined by the age-related depletion of the individual's homeostatic reserves, determining an increased susceptibility to stressors and disproportionate exposure to negative health changes. The physiological systems that are involved in the determination of frailty are mutually interrelated, so that when decline starts in a given system, implications may also regard the other systems. Indeed, it has been shown that the number of abnormal systems is more predictive of frailty than those of the abnormalities in any particular system. Delirium is a transient neurocognitive disorder, characterized by an acute onset and fluctuating course, inattention, cognitive dysfunction, and behavioral abnormalities, that complicates one out of five hospital admissions. Delirium is independently associated with the same negative outcomes of frailty and, like frailty, its pathogenesis is usually multifactorial, depending on complex inter-relationships between predisposing and precipitating factors. By definition, a somatic cause should be identified, or at least suspected, to diagnose delirium. Delirium and frailty potentially share multiple pathophysiologic mechanisms and pathways, meaning that they could be thought of as the two sides to the same coin. This review aims at summarizing the existing evidence, referring both to human and animal models, to postulate that delirium may represent the cognitive harbinger of a state of frailty in older persons experiencing an acute clinical event

Il riallestimento del Museo Astronomico di Brera

Grazie a uno stanziamento della Regione Lombardia ottenuto tramite il bando “Progetti di valorizzazione e promozione di Istituti, Luoghi della cultura, siti UNESCO, itinerari culturali e di catalogazione del patrimonio culturale - ambito museo 2019” tra il maggio e il dicembre 2020 è stato realizzato il nuovo allestimento della galleria del MusAB. Il MusAB ha in questa nuova esposizione l’ambizione di rispondere alla domanda “Cosa fa l’astronoma/o”? “Osservare, scoprire, misurare, rappresentare, sono queste le operazioni che compiono gli astronomi; noi cercheremo di illustrarle con l’aiuto degli antichi strumenti della Specola di Brera.” Così si legge nella rinnovata pannellistica del Museo mentre il telescopio Gualtieri, il Magnetometro, Boscovich e Napoleone ci guidano in prima persona alla scoperta di questa straordinaria disciplina. Van Gogh, Shakespeare, Tomasi di Lampedusa fanno da cornice alla visita e ci conducono fino a Marte dove il ricco patrimonio archivistico dell’INAF – Osservatorio Astronomico di Brera viene illustrato grazie alle riproduzioni digitali

Local spin dynamics at low temperature in the slowly relaxing molecular chain [Dy(hfac)3NIT(C6H4OPh)]: A &#956;+ spin relaxation study

The spin dynamics of the molecular magnetic chain [Dy(hfac)3NIT(C6H4OPh)] were investigated by means of the Muon Spin Relaxation (\u3bc+SR) technique. This system consists of a magnetic lattice of alternating Dy(III) ions and radical spins, and exhibits single-chain-magnet behavior. The magnetic properties of [Dy(hfac)3NIT(C6H4OPh)] have been studied by measuring the magnetization vs. temperature at different applied magnetic fields (H = 5, 3500, and 16500 Oe) and by performing \u3bc+SR experiments vs. temperature in zero field and in a longitudinal applied magnetic field H = 3500 Oe. The muon asymmetry P(t) was fitted by the sum of three components, two stretched-exponential decays with fast and intermediate relaxation times, and a third slow exponential decay. The temperature dependence of the spin dynamics has been determined by analyzing the muon longitudinal relaxation rate \u3bbinterm(T), associated with the intermediate relaxing component. The experimental \u3bbinterm(T) data were fitted with a corrected phenomenological Bloembergen-Purcell-Pound law by using a distribution of thermally activated correlation times, which average to \u3c4 = \u3c40 exp(\u394/kBT), corresponding to a distribution of energy barriers \u394. The correlation times can be associated with the spin freezing that occurs when the system condenses in the ground state