Assessment Of Circulating Endothelial Cells And Their Progenitors As Potential Biomarkers Of Disease Activity And Damage Accrual In Behçet's Syndrome

PURPOSE: To explore the potential role of circulating endothelial cells (CECs) and their progenitors (EPCs) as biomarkers of disease activity and damage accrual in patients with Behçet's syndrome (BS), by using a standardised and reliable flow cytometry protocol. PATIENTS AND METHODS: CECs and EPCs were assessed in 32 BS patients and 11 gender/age/smoking habits matched healthy controls (HC). They were identified by flow cytometry as alive/nucleated/CD45-negative/CD34-bright/CD146-positive and alive/nucleated/CD45-negative/CD34-bright/CD309-positive events, respectively. In BS patients, demographic and clinical features, including disease activity (assessed by Behçet's disease current disease activity form, BDCAF) and irreversible damage accrual (by the vasculitis damage index, VDI) were recorded. Uni- and multivariate analysis were performed to compare the CECs and EPCs concentrations in BS vs HC and to identify potential associations with demographic or clinical features. RESULTS: The CECs concentration was significantly higher in the BS patients than HCs [median (IQR) 15.0 (7.5-23.0) vs 6.0 (2.0-13.0) CECs/mL, p=0.024]. In BS patients, no significant associations were found between CECs and demographic features, present and past clinical manifestations, BDCAF score and ongoing treatment. A significant association was observed between CECs and organ damage, as assessed by the VDI (rho 0.356, p=0.045). Higher levels of CECs were especially associated with vascular damage [median (IQR) 23.0 (14.0-47.0) vs 13.0 (6.0-19.0) CECs/mL, p=0.011], including arterial aneurysm and stenosis, complicated venous thrombosis, cerebrovascular accident. The concentration of EPCs did not significantly differ between the BS and HC [median 26.5 (13.0-46.0) vs 19.0 (4.0-42.0) EPCs/mL, p=0.316] and no significant associations were observed between their levels and any clinical characteristic. CONCLUSION: Our study suggests that the CECs concentration is significantly higher in BS than healthy subjects, and it mainly correlates with vascular damage. A longitudinal extension of the present study on a wider cohort would be useful to validate the potential role of CECs as a marker or, hopefully, predictor of vascular damage in BS

Recent advances in structure and function of cytosolic IMP-GMP specific 5′nucleotidase II (cN-II)

Cytosolic 5′nucleotidase II (cN-II) catalyses both the hydrolysis of a number of nucleoside monophosphates (e.g., IMP + H2O→inosine + Pi), and the phosphate transfer from a nucleoside monophosphate donor to the 5′position of a nucleoside acceptor (e.g., IMP + guanosine →inosine + GMP). The enzyme protein functions through the formation of a covalent phosphoenzyme intermediate, followed by the phosphate transfer either to water (phosphatase activity) or to a nucleoside (phosphotransferase activity). It has been proposed that cN-II regulates the intracellular concentration of IMP and GMP and the production of uric acid. The enzyme might also have a potential therapeutic importance, since it can phosphorylate some anti-tumoral and antiviral nucleoside analogues that are not substrates of known kinases. In this review we summarise our recent studies on the structure, regulation and function of cN-II. Via a site-directed mutagenesis approach, we have identified the amino acids involved in the catalytic mechanism and proposed a structural model of the active site. A series of in vitro studies suggests that cN-II might contribute to the regulation of 5-phosphoribosyl-1-pyrophosphate (PRPP) level, through the so-called oxypurine cycle, and in the production of intracellular adenosine, formed by ATP degradation

The production of ionizing photons in UV-faint z~3-7 galaxies

The demographics of the production and escape of ionizing photons from UV-faint early galaxies is a key unknown in discovering the primary drivers of reionization. With the advent of JWST it is finally possible to observe the rest-frame optical nebular emission from individual sub-L$^*$ z>3 galaxies to measure the production of ionizing photons, $\xi_\mathrm{ion}$. Here we study a sample of 380 z~3-7 galaxies spanning -23 <M$_\mathrm{UV}$ < -15.5 (median M$_\mathrm{UV}\approx$ -18) with deep multi-band HST and JWST/NIRCam photometry covering the rest-UV to optical from the GLASS and UNCOVER JWST surveys. Our sample includes 109 galaxies with Lyman-alpha emission detected in MUSE spectroscopy. We use H-alpha fluxes inferred from NIRCam photometry to estimate the production rate of ionizing photons which do not escape these galaxies $\xi_\mathrm{ion}(1-f_\mathrm{esc})$. We find median $\log_{10}\xi_\mathrm{ion}(1-f_\mathrm{esc})=25.33\pm 0.47$, with a broad intrinsic scatter 0.42 dex, implying a broad range of galaxy properties and ages in our UV-faint sample. Galaxies detected with Lyman-alpha have ~0.1 dex higher $\xi_\mathrm{ion}(1-f_\mathrm{esc})$, which is explained by their higher H-alpha EW distribution, implying younger ages, higher sSFR and thus more O/B stars. We find significant trends of increasing $\xi_\mathrm{ion}(1-f_\mathrm{esc})$ with increasing H-alpha EW, decreasing UV luminosity, and decreasing UV slope, implying the production of ionizing photons is enhanced in young, low metallicity galaxies. We find no significant evidence for sources with very high ionizing escape fraction ($f_\mathrm{esc}$>0.5) in our sample, based on their photometric properties, even amongst the Lyman-alpha selected galaxies. This work demonstrates that considering the full distribution of $\xi_\mathrm{ion}$ across galaxy properties is important for assessing the primary drivers of reionization.Comment: 10 pages, 7 figures, submitted to A&

Early results from GLASS-JWST. III: Galaxy candidates at z∼\sim9-15

We present the results of a first search for galaxy candidates at z$\sim$9--15 on deep seven-bands NIRCam imaging acquired as part of the GLASS-JWST Early Release Science Program on a flanking field of the Frontier Fields cluster A2744. Candidates are selected via two different renditions of the Lyman-break technique, isolating objects at z$\sim$9-11, and z$\sim$9-15, respectively, supplemented by photometric redshifts obtained with two independent codes. We find six color-selected candidates at z$>$9, plus one additional candidate with photometric redshift z$_{phot}\geq$9. In particular, we identify two bright candidates at $m_{F150W}\simeq 26$ that are unambiguously placed at $z\simeq 10.6$ and $z\simeq 12.3$, respectively. The total number of galaxies discovered at $z>9$ is in line with the predictions of a non-evolving LF. The two bright ones at $z>10$ are unexpected given the survey volume, although cosmic variance and small number statistics limits general conclusions. This first search demonstrates the unique power of JWST to discover galaxies at the high redshift frontier. The candidates are ideal targets for spectroscopic follow-up in cycle$-2$.Comment: Submitted to ApJL, 9 pages, 4 figure

Early results from GLASS-JWST. XX: Unveiling a population of "red-excess'' galaxies in Abell2744 and in the coeval field

We combine JWST/NIRCam imaging and MUSE data to characterize the properties of galaxies in different environmental conditions in the cluster Abell2744 ($z=0.3064$) and in its immediate surroundings. We investigate how galaxy colors, morphology and star forming fractions depend on wavelength and on different parameterizations of environment. Our most striking result is the discovery of a ``red-excess'' population in F200W$-$F444W colors both in the cluster regions and the field. These galaxies have normal F115W$-$F150W colors, but are up to 0.8 mag redder than red sequence galaxies in F200W$-$F444W. They also have rather blue rest frame B$-$V colors. {Galaxies in the field and at the cluster virial radius are overall characterized by redder colors, but galaxies with the largest color deviations are found in the field and in the cluster core. Several results} suggest that mechanisms taking place in these regions might be more effective in producing these colors. Looking at their morphology, many cluster galaxies show signatures consistent with ram pressure stripping, while field galaxies have features resembling interactions and mergers. Our hypothesis is that these galaxies are characterized by dust enshrouded star formation: a JWST/NIRSpec spectrum for one of the galaxies is dominated by a strong PAH at 3.3$\mu m$, suggestive of dust obscured star formation. Larger spectroscopic samples are needed to understand if the color excess is due exclusively to dust-obscured star formation, and the role of environment in triggering it.Comment: ApJL in pres

Early Results from GLASS-JWST. XIX: A High Density of Bright Galaxies at z≈10z\approx10 in the Abell 2744 Region

We report the detection of a high density of redshift $z\approx 10$ galaxies behind the foreground cluster Abell 2744, selected from imaging data obtained recently with NIRCam onboard {\it JWST} by three programs -- GLASS-JWST, UNCOVER, and DDT\#2756. To ensure robust estimates of the lensing magnification $\mu$, we use an improved version of our model that exploits the first epoch of NIRCam images and newly obtained MUSE spectra, and avoids regions with $\mu>5$ where the uncertainty may be higher. We detect seven bright $z\approx 10$ galaxies with demagnified rest-frame $-22 \lesssim M_{\rm UV}\lesssim -19$ mag, over an area of $\sim37$ sq. arcmin. Taking into account photometric incompleteness and the effects of lensing on luminosity and cosmological volume, we find that the density of $z\approx 10$ galaxies in the field is about $10\times$ ($3\times$) larger than the average at $M_{UV}\approx -21~ (-20)$ mag reported so far. The density is even higher when considering only the GLASS-JWST data, which are the deepest and the least affected by magnification and incompleteness. The GLASS-JWST field contains 5 out of 7 galaxies, distributed along an apparent filamentary structure of 2 Mpc in projected length, and includes a close pair of candidates with $M_{\rm UV}< -20$ mag having a projected separation of only 16 kpc. These findings suggest the presence of a $z\approx 10$ overdensity in the field. In addition to providing excellent targets for efficient spectroscopic follow-up observations, our study confirms the high density of bright galaxies observed in early {\it JWST} observations, but calls for multiple surveys along independent lines of sight to achieve an unbiased estimate of their average density and a first estimate of their clustering.Comment: Accepted for publication in ApJL, 13 pages, 4 figure

Early results from GLASS-JWST. XIV: A spectroscopically confirmed protocluster 650 million years after the Big Bang

We present the spectroscopic confirmation of a protocluster at $z=7.88$ behind the galaxy cluster Abell2744 (hereafter A2744-z7p9OD). Using JWST NIRSpec, we find seven galaxies within a projected radius of 60kpc. Although the galaxies reside in an overdensity around $>20\times$ greater than a random volume, they do not show strong Lyman-alpha emission. We place 2-$\sigma$ upper limits on the rest-frame equivalent width $<16$-$28$AA. Based on the tight upper limits to the Lyman-alpha emission, we constrain the volume-averaged neutral fraction of hydrogen in the intergalactic medium to be $x_{\rm HI} > 0.45$ (68% CI). Using an empirical $M_{\rm UV}$-$M_{\rm halo}$ relation for individual galaxies, we estimate that the total halo mass of the system is $\gtrsim 4\times10^{11}\,M_\odot$. Likewise, the line of sight velocity dispersion is estimated to be $1100 \pm 200$km/s. Using an empirical relation, we estimate the present-day halo mass of A2744-z7p9OD to be $\sim2\times10^{15}\,M_\odot$, comparable to the Coma cluster. A2744-z7p9OD is the highest redshift spectroscopically confirmed protocluster to date, demonstrating the power of JWST to investigate the connection between dark-matter halo assembly and galaxy formation at very early times with medium-deep observations at $<20$hrs total exposure time. Follow-up spectroscopy of the remaining photometric candidates of the overdensity will further refine the features of this system and help characterize the role of such overdensities in cosmic reionization.Comment: The title has been updated to reflect the published numbering; a minor change has been made to Figure 1 with regard to the MSA shutters on the rgb stamp image. NASA press release article can be found at: https://www.nasa.gov/feature/goddard/2023/webb-reveals-early-universe-prequel-to-huge-galaxy-cluste

Roadmap on printable electronic materials for next-generation sensors

The dissemination of sensors is key to realizing a sustainable, ‘intelligent’ world, where everyday objects and environments are equipped with sensing capabilities to advance the sustainability and quality of our lives—e.g., via smart homes, smart cities, smart healthcare, smart logistics, Industry 4.0, and precision agriculture. The realization of the full potential of these applications critically depends on the availability of easy-to-make, low-cost sensor technologies. Sensors based on printable electronic materials offer the ideal platform: they can be fabricated through simple methods (e.g., printing and coating) and are compatible with high-throughput roll-to-roll processing. Moreover, printable electronic materials often allow the fabrication of sensors on flexible/stretchable/biodegradable substrates, thereby enabling the deployment of sensors in unconventional settings. Fulfilling the promise of printable electronic materials for sensing will require materials and device innovations to enhance their ability to transduce external stimuli—light, ionizing radiation, pressure, strain, force, temperature, gas, vapours, humidity, and other chemical and biological analytes. This Roadmap brings together the viewpoints of experts in various printable sensing materials—and devices thereof—to provide insights into the status and outlook of the field. Alongside recent materials and device innovations, the roadmap discusses the key outstanding challenges pertaining to each printable sensing technology. Finally, the Roadmap points to promising directions to overcome these challenges and thus enable ubiquitous sensing for a sustainable, ‘intelligent’ world

Multimodal force and temperature tactile sensor based on a short-channel organic transistor with high sensitivity

Abstract In this manuscript, we report on a novel architecture for the fabrication of highly sensitive multimodal tactile transducers, for the simultaneous detection of temperature and force. Such devices are based on a flexible Organic Charge Modulated Field Effect Transistor (OCMFET) coupled with a pyro/piezoelectric element, namely a commercial film of poly-vinylene difluoride (PVDF). The reduction of the channel length, obtained by employing a low-resolution vertical channel architecture, allowed to maximize the ratio between the sensing area and the transistor’s channel area, a technological approach that allows to considerably enhance both temperature and force sensitivity, while at the same time minimize the sensor’s dimensions. Thanks to the employment of a straightforward, up-scalable, and highly reproducible fabrication process, this solution represents an interesting alternative for all those applications requiring high-density, high-sensitivity sensors such as robotics and biomedical applications

Pentose phosphates in nucleoside interconversion and catabolism

Ribose phosphates are either synthesized through the oxidative branch of the pentose phosphate pathway, or are supplied by nucleoside phosphorylases. The two main pentose phosphates, ribose-5-phosphate and ribose-1-phosphate, are readily interconverted by the action of phosphopentomutase. Ribose-5-phosphate is the direct precursor of 5-phosphoribosyl-1-pyrophosphate, for both de novo and 'salvage' synthesis of nucleotides. Phosphorolysis of deoxyribonucleosides is the main source of deoxyribose phosphates, which are interconvertible, through the action of phosphopentomutase. The pentose moiety of all nucleosides can serve as a carbon and energy source. During the past decade, extensive advances have been made in elucidating the pathways by which the pentose phosphates, arising from nucleoside phosphorolysis, are either recycled, without opening of their furanosidic ring, or catabolized as a carbon and energy source. We review herein the experimental knowledge on the molecular mechanisms by which (a) ribose-1-phosphate, produced by purine nucleoside phosphorylase acting catabolically, is either anabolized for pyrimidine salvage and 5-fluorouracil activation, with uridine phosphorylase acting anabolically, or recycled for nucleoside and base interconversion; (b) the nucleosides can be regarded, both in bacteria and in eukaryotic cells, as carriers of sugars, that are made available though the action of nucleoside phosphorylases. In bacteria, catabolism of nucleosides, when suitable carbon and energy sources are not available, is accomplished by a battery of nucleoside transporters and of inducible catabolic enzymes for purine and pyrimidine nucleosides and for pentose phosphates. In eukaryotic cells, the modulation of pentose phosphate production by nucleoside catabolism seems to be affected by developmental and physiological factors on enzyme levels