Acidic microenvironment plays a key role in human melanoma progression through a sustained exosome mediated transfer of clinically relevant metastatic molecules

Background: Microenvironment cues involved in melanoma progression are largely unknown. Melanoma is highly influenced in its aggressive phenotype by the changes it determinates in its microenvironment, such as pH decrease, in turn influencing cancer cell invasiveness, progression and tissue remodelling through an abundant secretion of exosomes, dictating cancer strategy to the whole host. A role of exosomes in driving melanoma progression under microenvironmental acidity was never described. Methods: We studied four differently staged human melanoma lines, reflecting melanoma progression, under microenvironmental acidic pHs pressure ranging between pH 6.0-6.7. To estimate exosome secretion as a function of tumor stage and environmental pH, we applied a technique to generate native fluorescent exosomes characterized by vesicles integrity, size, density, markers expression, and quantifiable by direct FACS analysis. Functional roles of exosomes were tested in migration and invasion tests. Then we performed a comparative proteomic analysis of acid versus control exosomes to elucidate a specific signature involved in melanoma progression. Results: We found that metastatic melanoma secretes a higher exosome amount than primary melanoma, and that acidic pH increases exosome secretion when melanoma is in an intermediate stage, i.e. metastatic non-invasive. We were thus able to show that acidic pH influences the intercellular cross-talk mediated by exosomes. In fact when exposed to exosomes produced in an acidic medium, pH naïve melanoma cells acquire migratory and invasive capacities likely due to transfer of metastatic exosomal proteins, favoring cell motility and angiogenesis. A Prognoscan-based meta-analysis study of proteins enriched in acidic exosomes, identified 11 genes (HRAS, GANAB, CFL2, HSP90B1, HSP90AB1, GSN, HSPA1L, NRAS, HSPA5, TIMP3, HYOU1), significantly correlating with poor prognosis, whose high expression was in part confirmed in bioptic samples of lymph node metastases. Conclusions: A crucial step of melanoma progression does occur at melanoma intermediate -stage, when extracellular acidic pH induces an abundant release and intra-tumoral uptake of exosomes. Such exosomes are endowed with pro-invasive molecules of clinical relevance, which may provide a signature of melanoma advancement

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

The GAPS Programme at TNG. XXI. A GIARPS case study of known young planetary candidates: confirmation of HD 285507 b and refutation of AD Leonis b

Context. The existence of hot Jupiters is still not well understood. Two main channels are thought to be responsible for their current location: a smooth planet migration through the protoplanetary disk or the circularization of an initial highly eccentric orbit by tidal dissipation leading to a strong decrease in the semimajor axis. Different formation scenarios result in different observable effects, such as orbital parameters (obliquity and eccentricity) or frequency of planets at different stellar ages. Aims: In the context of the GAPS Young Objects project, we are carrying out a radial velocity survey with the aim of searching and characterizing young hot-Jupiter planets. Our purpose is to put constraints on evolutionary models and establish statistical properties, such as the frequency of these planets from a homogeneous sample. Methods: Since young stars are in general magnetically very active, we performed multi-band (visible and near-infrared) spectroscopy with simultaneous GIANO-B + HARPS-N (GIARPS) observing mode at TNG. This helps in dealing with stellar activity and distinguishing the nature of radial velocity variations: stellar activity will introduce a wavelength-dependent radial velocity amplitude, whereas a Keplerian signal is achromatic. As a pilot study, we present here the cases of two known hot Jupiters orbiting young stars: HD 285507 b and AD Leo b. Results: Our analysis of simultaneous high-precision GIARPS spectroscopic data confirms the Keplerian nature of the variation in the HD 285507 radial velocities and refines the orbital parameters of the hot Jupiter, obtaining an eccentricity consistent with a circular orbit. Instead, our analysis does not confirm the signal previously attributed to a planet orbiting AD Leo. This demonstrates the power of the multi-band spectroscopic technique when observing active stars. Photometry, RV, and time series are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/cat/J/A+A/638/A5 Based on observations made with the Italian Telescopio Nazionale Galileo (TNG) operated by the Fundación Galileo Galilei (FGG) of the Istituto Nazionale di Astrofisica (INAF) at the Observatorio del Roque de los Muchachos (La Palma, Canary Islands, Spain). Partly based on data obtained with the STELLA robotic telescopes in Tenerife, an AIP facility jointly operated by AIP and IAC

Concentric-flow electrokinetic injector enables serial crystallography of ribosome and photosystem II.

We describe a concentric-flow electrokinetic injector for efficiently delivering microcrystals for serial femtosecond X-ray crystallography analysis that enables studies of challenging biological systems in their unadulterated mother liquor. We used the injector to analyze microcrystals of Geobacillus stearothermophilus thermolysin (2.2-Å structure), Thermosynechococcus elongatus photosystem II (<3-Å diffraction) and Thermus thermophilus small ribosomal subunit bound to the antibiotic paromomycin at ambient temperature (3.4-Å structure)

GIARPS: commissioning and first scientific results

GIARPS (GIAno and haRPS) is a project devoted to have on the same focal station of the Telescopio Nazionale Galileo (TNG) both high resolution spectrographs, HARPS-N (VIS) and GIANO-B (NIR), working simultaneously. This could be considered the first and unique worldwide instrument providing cross-dispersed echelle spectroscopy at a resolution of 50,000 in the NIR range and 115,000 in the VIS and over in a wide spectral range (0.383-2.45 μm) in a single exposure. The science case is very broad, given the versatility of such an instrument and its large wavelength range. A number of outstanding science cases encompassing mainly extra-solar planet science starting from rocky planets search and hot Jupiters to atmosphere characterization can be considered. Furthermore both instruments can measure high precision radial velocities by means the simultaneous thorium technique (HARPS-N) and absorbing cell technique (GIANO-B) in a single exposure. Other science cases are also possible. GIARPS, as a brand new observing mode of the TNG started after the moving of GIANO-A (fiber fed spectrograph) from Nasmyth-A to Nasmyth-B where it was re-born as GIANO-B (no more fiber feed spectrograph). The official Commissioning finished on March 2017 and then it was offered to the community. Despite the work is not finished yet. In this paper we describe the preliminary scientific results obtained with GIANO-B and GIARPS observing mode with data taken during commissioning and first open time observations

Concentric-flow electrokinetic injector enables serial crystallography of ribosome and photosystem II.

We describe a concentric-flow electrokinetic injector for efficiently delivering microcrystals for serial femtosecond X-ray crystallography analysis that enables studies of challenging biological systems in their unadulterated mother liquor. We used the injector to analyze microcrystals of Geobacillus stearothermophilus thermolysin (2.2-Å structure), Thermosynechococcus elongatus photosystem II (<3-Å diffraction) and Thermus thermophilus small ribosomal subunit bound to the antibiotic paromomycin at ambient temperature (3.4-Å structure)

La conservazione ex situ della biodiversit\ue0 delle specie vegetali spontanee e coltivate in Italia. Stato dell'arte, criticit\ue0 e azioni da compiere.

Il presente documento riguarda lo stato della conservazione ex situ della biodiversit\ue0 vegetale in Italia, le criticit\ue0 riscontrate relativamente alle diverse componenti della flora (specie spontanee autoctone, forestali e coltivate) e le azioni da compiere in via prioritaria per risolvere i problemi pi\uf9acuti. Seppure destinati a \u201dinvecchiare\u201d, in molti casi sono stati elaborati i costi di alcune delle azioni da compiere per rendere concreto l\u2019impegno economico che, in taluni casi, la difesa della biodiversit\ue0 comporta. Sebbene perfettibile, il lavoro tenta di fornire una sintesi, con base rigorosamente scientifica, sulla conservazione ex situ della biodiversit\ue0 delle specie vegetali ed \ue8 perci\uf2 un contributo alla Strategia nazionale per la biodiversit\ue0