Chromatin dynamics of the developmentally regulated P. lividus neural alpha tubulin gene

Over 40 years ago, Allfrey and colleagues (1964) suggested that two histone modifications, namely acetylation and methylation, might regulate RNA synthesis. Nowadays it is universally accepted that activation of gene expression strictly depends on enzymatic mechanisms able to dynamically modify chromatin structure. Here, using techniques including DNaseI hypersensitive site analysis, chomatin immunoprecipitation and quantitative PCR analysis, we have analyzed the dynamics of histone post-translation modifications involved in developmentally/spatially controlled activation of the sea urchin PlTalpha2 tubulin gene. We have demonstrated that only when the PlTalpha2 core promoter chromatin is acetylated on H3K9, tri-methylated on H3K4 and not di-methylated on H3K27, RNA pol II can be enrolled. In contrast, we have shown that when chromatin is methylated both on H3K9 (me2/3) and H3K27 (me2) and mono methylated on H3K4 the promoter is not accessible to RNA pol II. Our results suggest that, during P. lividus embryogenesis, both HAT/HDAC and HMT/HDM activities, which are able to regulate accessibility of the PlTalpha2 basal promoter to RNA polymerase II, are coordinately switched-on

Augmented Project Management: Integrating Generative AI into the Agile Framework

openNegli ultimi anni i Large Language Models si stanno consolidando come uno strumento fondamentale per il supporto di lavoratori negli ambiti più disparati, in grado di aumentare l'efficienza e di ridurre il carico di lavoro per low level tasks. L'elaborato si propone quindi di esplorare le possibili applicazioni di questa tecnologia nel campo del Project Management concentrandosi in particolare sull'approccio Agile, il quale offre processi e metodologie chiave per i progetti dell'ambito software/ICT. Attraverso un'analisi delle tecniche di prompt engineering, il lavoro svolto mira quindi all'implementazione di un possibile approccio al Project Management (nello specifico Agile), basato sull'utilizzo di LLMs. L'obbiettivo è mostrare come una Generative AI possa essere usata come strumento per guidare e facilitare progetti Agile, contribuendo all'efficacia e alle competenze dei project manager e degli sviluppatori.Over the last few years, Large Language Models have consolidated themselves as an essential tool that offers support to workers in many different job positions, enhancing efficiency by reducing the amount of work in low level tasks and more. The study's aim is to explore the possible applications of this new technology in the field of Project Management, focusing specifically on the (relatively) new Agile approach, which offers key insights on processes and methods for software/ICT projects. Through the analysis of prompt engineering techniques, the thesis aims to integrate an approach to Project Management ( Agile PM) based on the employment of LLMs. The ultimate goal is to show how Generative AI can be used as a tool to guide and facilitate the management of Agile projects, contributing to the effectiveness and proficiency of project managers and developers

IGF-I induces upregulation of DDR1 collagen receptor in breast cancer cells by suppressing MIR-199a-5p through the PI3K/AKT pathway.

Discoidin Domain Receptor 1 (DDR1) is a collagen receptor tyrosine-kinase that contributes to epithelial-to-mesenchymal transition and enhances cancer progression. Our previous data indicate that, in breast cancer cells, DDR1 interacts with IGF-1R and positively modulates IGF-1R expression and biological responses, suggesting that the DDR1-IGF-IR cross-talk may play an important role in cancer.In this study, we set out to evaluate whether IGF-I stimulation may affect DDR1 expression. Indeed, in breast cancer cells (MCF-7 and MDA-MB-231) IGF-I induced significant increase of DDR1 protein expression, in a time and dose dependent manner. However, we did not observe parallel changes in DDR1 mRNA. DDR1 upregulation required the activation of the PI3K/AKT pathway while the ERK1/2, the p70/mTOR and the PKC pathways were not involved. Moreover, we observed that DDR1 protein upregulation was induced by translational mechanisms involving miR-199a-5p suppression through PI3K/AKT activation. This effect was confirmed by both IGF-II produced by cancer-associated fibroblasts from human breast cancer and by stable transfection of breast cancer cells with a human IGF-II expression construct. Transfection with a constitutively active form of AKT was sufficient to decrease miR-199a-5p and upregulate DDR1. Accordingly, IGF-I-induced DDR1 upregulation was inhibited by transfection with pre-miR-199a-5p, which also impaired AKT activation and cell migration and proliferation in response to IGF-I.These results demonstrate that, in breast cancer cells, a novel pathway involving AKT/miR-199a-5p/DDR1 plays a role in modulating IGFs biological responses. Therefore, this signaling pathway may represent an important target for breast cancers with over-activation of the IGF-IR axis

Sulla rilevanza dei piani regolatori dei porti (nota a Cons. Stato, Sez. VI, 28 dicembre 2020 n. 8356)

La nota muove alcuni rilievi critici all'interpretazione offerta dal Consiglio di Stato alla disciplina dettata dalla legge n. 84 del 1994 in materia di pianificazione portuale e all'inquadramento dato dal Giudice amministrativo al rapporto tra piani regolatori portuali e pianificazione urbanistic

A BIOMECHANICAL STUDY SHOULDER PAIN IN ELITE GYMNASTS

Introduction: Shoulder problems are common in overhead sports like baseball, basketball and volleyball. Although gymnastics consists of overhead activities, there are few studies of shoulder problems in this sport. During 1992-1995 we treated five young competitive gymnasts for shoulder pain. Arthroscopy revealed that all suffered from SLAP-lesions or other labral pathologies although they had never dislocated their shoulders. Since four of these athletes stated that they first became aware of acute shoulder pain during ring exercises in suspension, we decided to make an EMG-study of the shoulder musculature during exercises on the parallel bars and rings. Methods: Three elite gymnasts were investigated with telemetric surface EMG of the pect.maj., deltoid, biceps, triceps, trapezius and lat.dorsi. The gymnasts performed the standard bar and ring program. Results: During the ring exercises in suspension there was a ‘critical phase’ during which muscle activity around the shoulder was very low, leading to great articular stresses at the end of the ‘giant swing’, when their shoulders were suddenly exposed to a load of several times their body weight. EMG of biceps brachii was 67 µV just before the end of the giant swing and increased to 698µV. A similar tenfold increase was found in the other muscles as well. This probably explains the occurrence the SLAP lesions. A very strong pull in the long biceps tendon (before the muscle contracts) could tear loose the superior labrum and cause this socalled SLAP-lesion. Modifications of the rings or the ring exercises might decrease the occurrence of SLAP-lesions. Conclusion: Telemetric EMG analysis of the shoulder musculature during ring exercises provided an explanation for the occurrence of SLAP-lesions in gymnasts

Knowledge, attitudes and practices towards patients with HIV/AIDS in staff nurses in one university hospital in Sicily

Background: nurses’ knowledge, attitudes and practices towards patients with HIV/AIDS are of ongoing interest, especially in developing countries. Nothing or very little is known about Italian nurses. Methods: HIV/AIDS knowledge, attitudes and behaviours of the nurses (n=107) from one university hospital inCatania,Sicily, were documented. Comparisons among nurses belonging to different Operative Units (O.U.) were conducted by the chi-square test (P<0.05). Results: although HIV was nurses’ main concern in regard to contracting infections in the workplace (54%), the vast majority of them (98%) had never refused an HIV/AIDS patient care assignment. Moreover, despite their concern of being more at risk of contracting HIV than the general population (41%), a not negligible percentage of nurses did not use gloves routinely (21%) and only a few treated all patients as potentially HIV-positive (9%). The vast majority of the respondents knew the meaning of AIDS (87%) and of a positive serological test (78%). On the contrary, a relatively low percentage of them knew what is the ‘window period’ (62%) and were acquainted with HIV pathophysiology (65%). No statistically significant differences in terms of risk perception were found between nurses who had previously attended an HIV/AIDS workshop, lecture or specific course (43%) and nurses who did not (57%). Level of knowledge was positively associated to age (P=0.000) and to education (P=0.016), and it was found higher in nurses working in a O.U. of Infectious Diseases. Conclusions: data from our study show that also in developed countries, such as Italy, nurses could have some misconceptions and concerns about HIV/AIDS. The importance of examining the impact of continuing education on nurses’ preparedness to care for patients with HIV/AIDS and to prevent the risks of occupational HIV transmission is discussed.&nbsp

Unveil Intrahepatic Cholangiocarcinoma Heterogeneity through the Lens of Omics and Multi-Omics Approaches

Simple Summary Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive primary liver cancer leading to death in 10-15% of cases. In recent years, the iCCA worldwide incidence has been increasing, and research is currently focused on identifying valuable diagnostic biomarkers and developing specific therapies to counteract the disease despite its high heterogeneity. The use of cutting-edge and broad-spectrum applications like omics represents a successful approach to studying the intricate pathobiology of iCCA. In this review, we discuss how both single- and multi-omics studies can pave the way for identifying potential biomarkers, and more importantly, for stratifying iCCA patients. This stratification aims to enhance the therapeutic intervention through personalized medicine (PM).Abstract Intrahepatic cholangiocarcinoma (iCCA) is recognized worldwide as the second leading cause of morbidity and mortality among primary liver cancers, showing a continuously increasing incidence rate in recent years. iCCA aggressiveness is revealed through its rapid and silent intrahepatic expansion and spread through the lymphatic system leading to late diagnosis and poor prognoses. Multi-omics studies have aggregated information derived from single-omics data, providing a more comprehensive understanding of the phenomena being studied. These approaches are gradually becoming powerful tools for investigating the intricate pathobiology of iCCA, facilitating the correlation between molecular signature and phenotypic manifestation. Consequently, preliminary stratifications of iCCA patients have been proposed according to their "omics" features opening the possibility of identifying potential biomarkers for early diagnosis and developing new therapies based on personalized medicine (PM). The focus of this review is to provide new and advanced insight into the molecular pathobiology of the iCCA, starting from single- to the latest multi-omics approaches, paving the way for translating new basic research into therapeutic practices

The Intra-Group Baryons in the LEO I Pair From the VST Early-Type GAlaxy Survey

In this paper we present the deep, wide-field and multi-band imaging of the LEO I pair NGC 3379-NGC 3384, from the VST Early-type GAlaxy Survey (VEGAS). The main goal of this study is to map the intra-group baryons in the pair, in the form of diffuse light and globular clusters (GCs). Taking advantage from the large covered area, which extends for ∼ 3.9 square degrees around the pair, and the long integration time, we can map the light distribution out to ∼ 63 kpc and down to ∼ 30 mag/arcsec2 in the g band and ∼ 29 mag/arcsec2 in the r band, deeper than previous data available for this target. The map of the intra-group light (IGL) presents two very faint (μg ∼ 28-29 mag/arcsec2) streams protruding from the brightest group member NGC 3379 and elongated toward North-West and South. We estimate that the fraction of the stellar halo around NGC 3379 plus the intra-group light is (Formula presented.) in both g and r bands, with an average color g-r = 0.75 ± 0.04 mag. The color distribution of the GCs appears multi-modal, with two dominant peaks at (u-r) = 1.8 mag and (u-r) = 2.1 mag, respectively. The GC population stretches from North-East to South-West and from North-West to South of the pair, in the last case overlapping with the streams of IGL, as well as the PNe distribution found by Hartke et al. (Hartke et al., A&amp;A, 2020, 642, A46) and Hartke et al. (Hartke et al., 2022). Since these structures are elongated in the direction of the two nearby galaxies M96 and NGC 3338, they could be the remnant of a past gravitational interactions with the pair.</p

Advancements in the treatment of hypothyroidism with L-T4 liquid formulation or soft gel capsule: an update

INTRODUCTION: The most recent advance concerning levothyroxine (L-T4) therapy is the development of novel oral formulations: the liquid preparation, and the soft gel capsule. AREAS COVERED: This review evaluates the most recent clinical studies about these new formulations. The liquid formulation has been shown to overcome: the food and beverages intereference with L-T4 tablets absorption, caused by food or coffee at breakfast; malabsorption induced by the increased gastric pH, resulting from atrophic gastritis, or due to proton-pump inhibitors; and malabsorption after bariatric surgery. The use of liquid L-T4 has been studied also in pregnancy, newborns and infants, suggesting a better bioequivalence than tablets. Finally, liquid L-T4 is more active than tablets in the control of thyroid-stimulating hormone (TSH) in hypothyroid patients without malabsorption, drug interference, or gastric disorders, leading to a hypothesized higher absorption of liquid L-T4 also in these patients. Few studies have evaluated soft gel L-T4 with promising results in patients with malabsorption related to coffee or gastritis. EXPERT OPINION: Liquid L-T4 (and soft gel capsules) are more active than the tablet L-T4 in the control of TSH in hypothyroid patients with gastric disorders, malabsorption, or drug interference, but also in patients without absorption disorders