MIR205HG/LEADR Long Noncoding RNA Binds to Primed Proximal Regulatory Regions in Prostate Basal Cells Through a Triplex- and Alu-Mediated Mechanism

Aside serving as host gene for miR-205, MIR205HG transcribes for a chromatin-associated long noncoding RNA (lncRNA) able to restrain the differentiation of prostate basal cells, thus being reannotated as LEADR (Long Epithelial Alu-interacting Differentiation-related RNA). We previously showed the presence of Alu sequences in the promoters of genes modulated upon MIR205HG/LEADR manipulation. Notably, an Alu element also spans the first and second exons of MIR205HG/LEADR, suggesting its possible involvement in target selection/binding. Here, we performed ChIRP-seq to map MIR205HG/LEADR chromatin occupancy at genome-wide level in prostate basal cells. Our results confirmed preferential binding to regions proximal to gene transcription start site (TSS). Moreover, enrichment of triplex-forming sequences was found upstream of MIR205HG/LEADR-bound genes, peaking at −1,500/−500 bp from TSS. Triplexes formed with one or two putative DNA binding sites within MIR205HG/LEADR sequence, located just upstream of the Alu element. Notably, triplex-forming regions of bound genes were themselves enriched in Alu elements. These data suggest, from one side, that triplex formation may be the prevalent mechanism by which MIR205HG/LEADR selects and physically interacts with target DNA, from the other that direct or protein-mediated Alu (RNA)/Alu (DNA) interaction may represent a further functional requirement. We also found that triplex-forming regions were enriched in specific histone modifications, including H3K4me1 in the absence of H3K27ac, H3K4me3 and H3K27me3, indicating that in prostate basal cells MIR205HG/LEADR may preferentially bind to primed proximal regulatory elements. This may underscore the need for basal cells to keep MIR205HG/LEADR target genes repressed but, at the same time, responsive to differentiation cues

Cardiac Baroreflex, HRV, and Statistics: An Interdisciplinary Approach in Hypertension

Interests about the fine underpinnings of cardiovascular beat-by-beat variability have historical roots. Over the last decades, various aspects of the relationships between arterial pressure and heart period were taken as a proxy of the baroreflex in physiology and medicine, stimulating the interest of investigators in several interconnected scientific fields, in particular, bioengineering, neurophysiology, and clinical medicine. Studies of the overall system facilitated the emergence of a simplified negative (vagal) feedback model of the baroreflex and overshadowed the simultaneous interaction with excitatory, sympathetic positive-feedback mechanisms that would, however, better suit the model of a “paired antagonistic (parasympathetic/sympathetic) innervation of the internal organs.” From the bioengineering side, the simplicity of obtaining the series of subsequent RR intervals stimulated the analysis of beat-by-beat variations, providing a multitude of heart rate variability (HRV) indices considered as proxies of the underlying sympatho-vagal balance, and participating to the management of several important clinical conditions, such as hypertension. In this context, advanced statistical methods, used in an integrated manner and controlling for age and gender biases, might help shed new light on the relationship between cardiac baroreflex, assessed by the frequency domain index α, and the HRV indices with the varying of systolic arterial pressure (SAP) levels. The focus is also on a novel unitary Autonomic Nervous System Index (ANSI) built as a synthesis of HRV considering its three most informative proxies [RR, RR variance, and the rest-stand difference in the normalized power of low-frequency (LF) variability component]. Data from a relatively large set of healthy subjects (n = 1154) with a broad range of SAP [from normal (nNt = 778) to elevated (nHt = 232)] show that, e.g., α and ANSI significantly correlate overall (r = 0.523, p < 0.001), and that this correlation is lower in hypertensives (r = 0.444, p < 0.001) and higher in pre-hypertensives (r = 0.618, p < 0.001) than in normotensives (r = 0.5, p < 0.001). That suggests the existence of curvilinear “umbrella” patterns that might better describe the effects of the SAP states on the relationships between baroreflex and HRV. By a mix of robust, non-parametric and resampling statistical techniques, we give empirical support to this study hypothesis and show that the pre-hypertensive group results at the apex/bottom in most of the studied trends

Influenza A/H1N1/2009 virus - experience of the clinical microbiology laboratory of the "L. Sacco" University Hospital in Milan

In the spring of 2009, a new variant of influenza A/H1N1 virus that had never been isolated before, was identified. From April 27 to December 31, 2009 the respiratory samples of 974 patients, obtained from suspected cases of pandemic influenza A virus infection, were analyzed at the Clinical Microbiology Laboratory of the "L. Sacco" University Hospital in Milan. The diagnosis of influenza A/H1N1 infection was performed initially through the use of different molecular biological methods: Seeplex® RV12 ACE Detection (Seegene), NUCLISENS® EASYQ® INFLUENZA A/B (bioMérieux), Influenza A/B Q-PCR Alert (Nanogen) running in parallel with rRT-PCR (CDC) to confirm the positivity to the new influenza virus, then was used a single specific test, Fast set H1N1v (Arrow Diagnostics). Retrospective study of data showed that 293 (30.1%) patients were positive for the new strain of influenza A/H1N1 virus and 8 (0.8%) for influenza A other than H1N1 virus.The distribution of influenza A/H1N1 cases showed two peaks, one on July (62.9%) and the other one on October (36%), moreover we observed that 155 patients (53%) out of 293 positive for influenza A/H1N1 virus aged under 20 years old. The first positivity peak was found in travelers and the second one, occurred 2-3 months prior to the classic seasonal epidemic influenza, was attributed to autochthonous cases , by which the virus had spread worldwide. The highest proportion of cases were among subjects aged from 0 to 20 years and, over this age the positivity rate decreased proportionally with increasing age, in agreement with data reported in other countries

A Spitzer Space Telescope survey of massive young stellar objects in the G333.2-0.4 giant molecular cloud

The G333 giant molecular cloud contains a few star clusters and H II regions, plus a number of condensations currently forming stars. We have mapped 13 of these sources with the appearance of young stellar objects (YSOs) with the Spitzer Infrared Spectrograph in the SL, SH, and LH modules (5-36 micron). We use these spectra plus available photometry and images to characterize the YSOs. The spectral energy distributions (SEDs) of all sources peak between 35 and 110 micron, thereby showing their young age. The objects are divided into two groups: YSOs associated with extended emission in IRAC band 2 at 4.5 micron (`outflow sources') and YSOs that have extended emission in all IRAC bands peaking at the longest wavelengths (`red sources'). The two groups of objects have distinctly different spectra: All the YSOs associated with outflows show evidence of massive envelopes surrounding the protostar because the spectra show deep silicate absorption features and absorption by ices at 6.0, 6.8, and 15.2 micron. We identify these YSOs with massive envelopes cool enough to contain ice-coated grains as the `bloated' protostars in the models of Hosokawa et al. All spectral maps show ionized forbidden lines and PAH emission features. For four of the red sources, these lines are concentrated to the centres of the maps, from which we infer that these YSOs are the source of ionizing photons. Both types of objects show evidence of shocks, with most of the outflow sources showing a line of [S I] in the outflows and two of the red sources showing the more highly excited [Ne III] and [S IV] lines in outflow regions at some distance from the YSOs. The 4.5 micron emission seen in the IRAC band 2 images of the outflow sources is not due to H2 lines, which are too faint in the 5-10 micron wavelength region to be as strong as is needed to account for the IRAC band 2 emission.Comment: 31 pages and 30 figures in the paper plus 11 figures from the online Supporting Information. To be published in the MNRAS. Version 2 has many small changes (typos, spelling, punctuation) and reordering of the Supporting Information figures to make this version conform to the paper that will be printed in MNRA

Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action

Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or “golden rules,” for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Tra argomentazione e interazione in italiano L2

L'articolo verte sull'uso del dibattito come attivit\ue0 per l'inasegnamento dell'italiano L2 a studenti universitari non italofoni. il dibattere \ue8 un\u2019attivit\ue0 che presenta diversi vantaggi: innanzitutto , l\u2019argomentazione mette in gioco competenze cognitive trasversali alle specifiche lingue; in secondo luogo, permette di esercitare la propria competenza interazionale in una L2; infine, al \u201csaper fare\u201d in italiano si aggiunge una dimensione di apprendimento pi\uf9 generale mediata dalla L2. Nell'articolo ci si focalizza sulla competenza interazionale, analizzando l'inizio di un dibattito tra due studentesse che ha costituito la prova d'esame finale di un lettorato di 20 ore, parte dell\u2019insegnamento opzionale di Lingua Italiana L2 (60 ore complessive per 6 CFU) diretto a studenti in mobilit\ue0 e studenti non italofoni iscritti al Corso di Laurea Triennale di Mediazione Linguistica e Interculturale del Dipartimento di Interpretazione e Traduzione (universit\ue0 di Bologna). Pi\uf9 precisamente, il dibattito \ue8 stato analizzato attraverso tre parametri, dei quali i primi due sono considerati come caratteristiche chiave per valutare la competenza interazionale, mentre il terzo \ue8 strettamente legato alla componente argomentativa del compito: - le modalit\ue0 di sviluppo del topic, in particolare la capacit\ue0 di espandere quello altrui, collegando il proprio intervento a quello del compagno; - le mosse dell\u2019ascoltatore a supporto del parlante, in particolare backchanneling, e conferma e/o verifica della comprensione, ecc. ; - il modo in cui vengono utilizzate le espressioni di accordo all\u2019interno di un task di tipo divergente e le espressioni usate in apertura di turno, che spesso sono anche strategie per esprimere accordo/disaccordo

Autonomic Differentiation Map: A Novel Statistical Tool for Interpretation of Heart Rate Variability

In spite of the large body of evidence suggesting Heart Rate Variability (HRV) alone or combined with blood pressure variability (providing an estimate of baroreflex gain) as a useful technique to assess the autonomic regulation of the cardiovascular system, there is still an ongoing debate about methodology, interpretation, and clinical applications. In the present investigation, we hypothesize that non-parametric and multivariate exploratory statistical manipulation of HRV data could provide a novel informational tool useful to differentiate normal controls from clinical groups, such as athletes, or subjects affected by obesity, hypertension, or stress. With a data-driven protocol in 1,352 ambulant subjects, we compute HRV and baroreflex indices from short-term data series as proxies of autonomic (ANS) regulation. We apply a three-step statistical procedure, by first removing age and gender effects. Subsequently, by factor analysis, we extract four ANS latent domains that detain the large majority of information (86.94%), subdivided in oscillatory (40.84%), amplitude (18.04%), pressure (16.48%), and pulse domains (11.58%). Finally, we test the overall capacity to differentiate clinical groups vs. control. To give more practical value and improve readability, statistical results concerning individual discriminant ANS proxies and ANS differentiation profiles are displayed through peculiar graphical tools, i.e., significance diagram and ANS differentiation map, respectively. This approach, which simultaneously uses all available information about the system, shows what domains make up the difference in ANS discrimination. e.g., athletes differ from controls in all domains, but with a graded strength: maximal in the (normalized) oscillatory and in the pulse domains, slightly less in the pressure domain and minimal in the amplitude domain. The application of multiple (non-parametric and exploratory) statistical and graphical tools to ANS proxies defines differentiation profiles that could provide a better understanding of autonomic differences between clinical groups and controls. ANS differentiation map permits to rapidly and simply synthesize the possible difference between clinical groups and controls, evidencing the ANS latent domains that have at least a medium strength of discrimination, while the significance diagram permits to identify the single ANS proxies inside each ANS latent domain that resulted in significant comparisons according to statistical tests