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Context. Classical T Tauri stars (cTTs) accrete from their circumstellar disk. The material falls onto the stellar surface, producing an accretion shock, which generates veiling in a star's spectra. In addition, the shock causes a localized accretion spot at the level of the chromosphere. Aims. Our goal is to investigate the accretion, particularly the mass accretion rates (Ṁacc), for the cTTs DK Tau, over two periods of 17 and 29 days, using two different procedures for comparison purposes. Methods. The first method relies on the derivation of the accretion luminosity via accretion-powered emission lines. The second compares the variability of the optical veiling with accretion shock models to determine mass accretion rates. We used observations taken in 2010 and 2012 with the ESPaDOnS (Echelle SpectroPolarimetric Device for the Observation of Stars) spectropolarimeter at the CFHT (Canada-France-Hawaii Telescope). Results. We find peak values of the veiling (at ∼550 nm) ranging from 0.2 to 1.3, with a steeper trend across the wavelength range for higher peak values. When using the accretion-powered emission lines, we find mass accretion rate values ranging from log (Ṁacc[M⊙ yr−1]) = −8.20 to log (Ṁacc[M⊙ yr−1]) = −7.40. This agrees with the values found in the literature, as well as the values calculated using the accretion shock models and the veiling. In addition, we identify a power-law correlation between the values of the accretion luminosity and the optical veiling. For the 2010 observations, using the values of the filling factors (which represent the area of the star covered by an accretion spot) derived from the shock models, we infer that the accretion spot was located between +45° and +75° in latitude. Conclusion. We show that both methods of determining the mass accretion rate yield similar results. We also present a helpful means of confirming the accretion luminosity values by measuring the veiling at a single wavelength in the optical. [ABSTRACT FROM AUTHOR]

Background: Onychopapilloma (OP) is a benign longitudinal nail bed tumour usually presenting as longitudinal erythronychia. Evidence‐based recommendations for proper histologic sectioning and definitive surgical management are not available. Objectives: The aim of this study was threefold. The first was to review the clinical and histopathological features of all OP diagnosed in our department. The second was to identify the most accurate histological technique. The third aim was to determine the most effective surgical procedures by examining recurrence rates and complications over the long term. Methods: This retrospective analysis collected all patients with OP in the dermatology department of Saint‐Pierre – Brugmann University Hospital (Brussels, Belgium) between January 2007 and March 2017. Clinical findings and type of surgery performed were recorded from medical files and iconographic documents. All slides were reviewed by a dermatopathologist with expertise in nail disease. Longitudinal follow‐up was performed. Results: A total of 68 patients were included (42 women, 26 men) with a median age of 46 years. Two children were 9 and 11. The histological interpretation was more difficult for the transverse sections than for the longitudinal ones (29.4% vs. 2.2%). The pathological diagnosis of OP was typical in 30.6%, suggestive in 51.6%, slightly suggestive in 12.9% and not contributive in 4.8%. 50 patients had a mean follow‐up of 50 months. 38% recovered completely and 20% recurred. 42% had mild to moderate sequelae. Conclusions: We report herein the first two paediatric cases. Classical longitudinal excision with careful removal of the lesion from the inferior face of the nail plate seems to be the most accurate surgical technique. In the pathology laboratory, longitudinal sections should be recommended. In our series, a recurrence rate of 20% was observed. This was more frequent when a tangential longitudinal excision was performed. Linked article: This article is commented on by E. Haneke, pp. 1839–1840 in this issue. To view this articlehttps://doi.org/10.1111/jdv.14966 [ABSTRACT FROM AUTHOR]

Context. Afterglows of gamma-ray bursts (GRBs) are simple in the most basic model, but can show many complex features. The ultra-long duration GRB 111209A, one of the longest GRBs ever detected, also has the best-monitored afterglow in this rare class of GRBs. Aims. We want to address the question whether GRB 111209A was a special event beyond its extreme duration alone, and whether it is a classical GRB or another kind of high-energy transient. The afterglow may yield significant clues. Methods. We present afterglow photometry obtained in seven bands with the GROND imager as well as in further seven bands with the Ultraviolet/Optical Telescope (UVOT) on-board the Neil Gehrels Swift Observatory. The light curve is analysed by multi-band modelling and joint fitting with power-laws and broken power-laws, and we use the contemporaneous GROND data to study the evolution of the spectral energy distribution. We compare the optical afterglow to a large ensemble we have analysed in earlier works, and especially to that of another ultra-long event, GRB 130925A. We furthermore undertake a photometric study of the host galaxy. Results. We find a strong, chromatic rebrightening event at ≈0.8 days after the GRB, during which the spectral slope becomes redder. After this, the light curve decays achromatically, with evidence for a break at about 9 days after the trigger. The afterglow luminosity is found to not be exceptional. We find that a double-jet model is able to explain the chromatic rebrightening. The afterglow features have been detected in other events and are not unique. Conclusions. The duration aside, the GRB prompt emission and afterglow parameters of GRB 111209A are in agreement with the known distributions for these parameters. While the central engine of this event may differ from that of classical GRBs, there are multiple lines of evidence pointing to GRB 111209A resulting from the core-collapse of a massive star with a stripped envelope. [ABSTRACT FROM AUTHOR]

Context. Deriving physical parameters from gamma-ray burst (GRB) afterglow observations remains a challenge, even 20 years after the discovery of afterglows. The main reason for the lack of progress is that the peak of the synchrotron emission is in the sub-mm range, thus requiring radio observations in conjunction with X-ray/optical/near-infrared data in order to measure the corresponding spectral slopes and consequently remove the ambiguity with respect to slow vs. fast cooling and the ordering of the characteristic frequencies. Aims. We have embarked on a multifrequency, multi-epoch observing campaign to obtain sufficient data for a given GRB that allows us to test the simplest version of the fireball afterglow model. Methods. We observed GRB 151027B, the 1000th Swift-detected GRB, with GROND in the optical–near-IR, ALMA in the sub-millimeter, ATCA in the radio band; we combined this with public Swift/XRT X-ray data. Results. While some observations at crucial times only return upper limits or surprising features, the fireball model is narrowly constrained by our data set, and allows us to draw a consistent picture with a fully determined parameter set. Surprisingly, we find rapid, large-amplitude flux density variations in the radio band which are extreme not only for GRBs, but generally for any radio source. We interpret them as scintillation effects, though their extreme nature requires the scattering screen to be at a much smaller distance than usually assumed, multiple screens, or a combination of the two. Conclusions. The data are consistent with the simplest fireball scenario for a blast wave moving into a constant-density medium, and slow-cooling electrons. All fireball parameters are constrained at or better than a factor of 2, except for the density and the fraction of the energy in the magnetic field which has a factor of 10 uncertainty in both directions. [ABSTRACT FROM AUTHOR]

Context. Short-duration gamma-ray bursts (GRBs) with extended emission form a subclass of short GRBs, comprising about 15% of the short-duration sample. Afterglow detections of short GRBs are also rare (about 30%) because of their lower luminosity. Aims.We present a multiband data set of the short burst with extended emission, GRB 150424A, comprising of GROND observations, complemented with data from Swift/UVOT, Swift/XRT, HST, Keck/LRIS, and data points from the literature. The GRB 150424A afterglow shows an extended plateau phase, lasting about 8 h. The analysis of this unique GRB afterglow might shed light on the understanding of afterglow plateau emission, the nature of which is still under debate. Methods.We present a phenomenological analysis made by applying fireball closure relations and interpret the findings in the context of the fireball model. We discuss the plausibility of a magnetar as a central engine, which would be responsible for additional and prolonged energy injection into the fireball. Results. We find convincing evidence for energy injection into the afterglow of GRB 150424A. We find that a magnetar spin-down as the source for a prolonged energy injection requires that at least 4% of the spin-down energy is converted into radiation. [ABSTRACT FROM AUTHOR]

We present new photometric observations of H1413+117 acquired during seasons between 2001 and 2008 in order to estimate the time delays between the lensed quasar images and to characterize at best the on-going micro-lensing events. We propose a highly performing photometric method called the adaptive point spread function fitting and have successfully tested this method on a large number of simulated frames. This has enabled us to estimate the photometric error bars affecting our observational results.We analysed the V- and R-band light curves and V-R colour variations of the A-D components which show short- and long-term brightness variations correlated with colour variations. Using the X2 and dispersion methods, we estimated the time delays on the basis of the R-band light curves over the seasons between 2003 and 2006. We have derived the new values: ΔtAB=-17.4 ± 2.1,ΔtAC =-18.9 ±2.8 and ΔtAD = 28.8 ± 0.7 d using the X2 method (B and C are leading, D is trailing) with 1σ confidence intervals. We also used available observational constraints (resp. the lensed image positions, the flux ratios in mid-IR and two sets of time delays derived in the present work) to update the lens redshift estimation.We obtained z1 = 1.95+0.06 which is in good agreement with previous estimations. We propose to characterize two kinds of micro-lensing events: micro-lensing for the A, B, C components corresponds to typical variations of ~10-0.10 which is in good agreement with previous estimations. We propose to characterize two kinds of micro-lensing events: micro-lensing for the A, B, C components corresponds to typical variations of ~10-4 mag d-1 during all the seasons, while the D component shows an unusually strong micro-lensing effect with variations of up to ~10-3 mag d-1 during 2004 and 2005. [ABSTRACT FROM AUTHOR]

We report on the results of a ~40-d multi-wavelength monitoring of the Be X-ray binary system IGR J05007-7047 (LXP 38.55). During that period the system was monitored in the X-rays using the Swift telescope and in the optical with multiple instruments. When the X-ray luminosity exceeded 1036 erg s-1 we triggered an XMM-Newton ToO observation. Timing analysis of the photon events collected during the XMM-Newton observation reveals coherent X-ray pulsations with a period of 38.551(3) s (1σ), making it the 17th known high-mass X-ray binary pulsar in the LMC. During the outburst, the X-ray spectrum is fitted best with a model composed of an absorbed power law (Γ = 0.63) plus a high-temperature blackbody (kT ~2 keV) component. By analysing ~12 yr of available OGLE optical data we derived a 30.776(5) d optical period, confirming the previously reported X-ray period of the system as its orbital period. During our X-ray monitoring the system showed limited optical variability while its IR flux varied in phase with the X-ray luminosity, which implies the presence of a disc-like component adding cooler light to the spectral energy distribution of the system. [ABSTRACT FROM AUTHOR]

We report the early discovery of the optical afterglow of gamma-ray burst (GRB) 140801A in the 137 deg2 3-σ error-box of the Fermi Gamma-ray Burst Monitor (GBM). MASTER is the only observatory that automatically reacts to all Fermi alerts. GRB 140801A is one of the few GRBs whose optical counterpart was discovered solely from its GBM localization. The optical afterglow of GRB 140801A was found by MASTER Global Robotic Net 53 s after receiving the alert, making it the fastest optical detection of a GRB from a GBM error-box. Spectroscopy obtained with the 10.4-m Gran Telescopio Canarias and the 6-m Big Telescope Alt-azimuth of the Special Astrophysical Observatory of the Russian Academy of Sciences reveals a redshift of z = 1.32. We performed optical and near-infrared photometry of GRB 140801A using different telescopes with apertures ranging from 0.4 to 10.4 m. GRB 140801A is a typical burst in many ways. The rest-frame bolometric isotropic energy release and peak energy of the burst are Eiso = 5.54+0.26-0.24 × 1052 erg and Ep, rest ≃280 keV, respectively, which is consistent with the Amati relation. The absence of a jet break in the optical light curve provides a lower limit on the half-opening angle of the jet θ = 6°.1. The observed Epeak is consistent with the limit derived from the Ghirlanda relation. The joint Fermi GBM and Konus-Wind analysis show that GRB 140801A could belong to the class of intermediate duration. The rapid detection of the optical counterpart of GRB 140801A is especially important regarding the upcoming experiments with large coordinate error-box areas. [ABSTRACT FROM AUTHOR]

Over the last decade there has been immense progress in the follow-up of short and long gamma-ray bursts (GRBs), resulting in a significant rise in the detection rate of X-ray and optical afterglows, in the determination of GRB redshifts, and of the identification of the underlying host galaxies. Nevertheless, our theoretical understanding of the progenitors and central engines powering these vast explosions is lagging behind, and a newly identified class of ultra-long GRBs has fuelled speculation on the existence of a new channel of GRB formation. In this paper we present high signal-to-noise X-Shooter observations of the host galaxy of GRB 130925A, which is the fourth unambiguously identified ultra-long GRB, with prompt γ-ray emission detected for ∼20 ks. The GRB line of sight was close to the host galaxy nucleus, and our spectroscopic observations cover this region along the bulge/disk of the galaxy and a bright star-forming region within the outskirts of the galaxy. From our broad wavelength coverage, we obtain accurate metallicity and dust-extinction measurements at the galaxy nucleus and at an outer star-forming region, and measure a super-solar metallicity at both locations, placing this galaxy within the 10-20% most metal-rich GRB host galaxies. Such a high metal enrichment has significant implications on the progenitor models of both long and ultra-long GRBs, although the edge-on orientation of the host galaxy does not allow us to rule out a large metallicity variation along our line of sight. The spatially resolved spectroscopic observations presented in this paper offer important insight into variations in the metal and dust abundance within GRB host galaxies. However, they also illustrate the need for integral field unit observations on a larger sample of GRB host galaxies of a variety of metallicities to provide a more quantitative view on the relation between the GRB circumburst environment and the galaxy-whole properties. [ABSTRACT FROM AUTHOR]

Fast radio bursts (FRBs) are one of the most tantalizing mysteries of the radio sky; their progenitors and origins remain unknown and until now no rapid multiwavelength follow-up of an FRB has been possible. New instrumentation has decreased the time between observation and discovery from years to seconds, and enables polarimetry to be performed on FRBs for the first time. We have discovered an FRB (FRB 140514) in real-time on 2014 May 14 at 17:14:11.06 UTC at the Parkes radio telescope and triggered follow-up at other wavelengths within hours of the event. FRB 140514 was found with a dispersion measure (DM) of 562.7(6) cm-3 pc, giving an upper limit on source redshift of z ≲ 0.5. FRB 140514 was found to be 21 ± 7 per cent (3s) circularly polarized on the leading edge with a 1σ upper limit on linear polarization <10 per cent. We conclude that this polarization is intrinsic to the FRB. If there was any intrinsic linear polarization, as might be expected from coherent emission, then it may have been depolarized by Faraday rotation caused by passing through strong magnetic fields and/or high-density environments. FRB 140514 was discovered during a campaign to re-observe known FRB fields, and lies close to a previous discovery, FRB 110220; based on the difference in DMs of these bursts and time-on-sky arguments, we attribute the proximity to sampling bias and conclude that they are distinct objects. Follow-up conducted by 12 telescopes observing from X-ray to radio wavelengths was unable to identify a variable multiwavelength counterpart, allowing us to rule out models in which FRBs originate from nearby (z < 0.3) supernovae and long duration gamma-ray bursts. [ABSTRACT FROM AUTHOR]

Abstract: We analysed Si isotopic signatures (δ30Si signature) of dissolved silicon (DSi) in the Scheldt (Belgium) tidal river (four stations) and in its main tributaries (Zenne, Dender, Grote Nete and Kleine Nete). For each station, we analysed four samples representative of the four seasons. These are the first δ30Si data at the basin and seasonal scales measured in a watershed under high anthropogenic pressure. In the Scheldt main stem, we show that the role of diatoms on the silicon biogeochemical cycle and δ30Si signatures is dominant in summer and sometimes in fall. Out of the diatoms' growing season, the Scheldt main stem exhibits unexpected large δ30Si signatures variations, especially in winter. Although these isotopic variations are not reflected in DSi concentrations, they are consistent with δ30Si signatures recorded in the main tributaries. This indicates that except for summer diatom blooms, δ30Si signatures in the tidal river result from a conservative mixing with tributaries. Overall we suggest that the variations are mainly set by land use and lithology at the sub-basin level. Forest cover (inducing clay dissolution favoured by the presence of humic acids) and wetland cover (yielding to dissolution of biogenic silica) are highly and significantly correlated with δ30Si (R2 >0.85). Both environments tend to render the tributaries δ30Si signatures lighter while agriculture cover has the reverse effect on δ30Si values (R2 =0.70, p-value<0.08). In contrast, urban zone cover does not have any noticeable effect on Si isotopic signatures of the Scheldt tributaries. Despite this effect of land use, we estimate a mean annual δ30Si signature output from the Scheldt tidal river to the saline estuary at 0.95‰, well comparable to other rivers. This results from the mixing of tributaries within the tidal river which levels off at the outlet the Si isotopic differences of the sub-basins. In the Scheldt watershed, it thus seems that Si isotopes could trace anthropogenic activities at the sub-basin scale. In contrast, at the outlet, the variety of land-use and lithology found over the whole watershed are merged into a mean isotopic signature similar to the world river average. As it is now recognised that change in land use alter the silicon biogeochemical continental cycle, our data show that use of Si isotopic signatures might constitute a useful proxy to better trace these modifications on contrasted (sub-)basins. [Copyright &y& Elsevier]

The acyclic nucleoside phosphonate (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) was used topically for the treatment of persistent mucocutaneous infections in two cases. One patient with AIDS suffered from a perineal lesion due to infection with herpes simplex virus type 2 (HSV-2) and did not respond to acyclovir and was intolerant of foscamet. A bone marrow transplant recipient developed orofacial lesions due to infection with herpes simplex virus type 1 (HSV-1) that failed to respond to therapy with both acyclovir and foscarnet. After topical application of HPMPC, the HSV-2 lesions completely resolved. However, the lesions recurred 3 weeks later, and, upon subsequent treatment with HPMPC, regressed. On recurrence, the virus was found to be sensitive to acyclovir, which the patient was given. Again HSV-2, which was resistant to acyclovir, emerged; similar observations were made after another cycle of HPMPC therapy. The HSV-1 isolates were resistant to acyclovir and foscarnet. Following local HPMPC treatment, the lesions regressed, but after 1 week, a second course of topical HPMPC therapy had to be instituted for recurrent infection. The lesions again regressed, and as the recurrent virus was sensitive to acyclovir, the patient was successfully treated with the drug. The results of this study point to the potential usefulness of topical HPMPC in the treatment of immunocompromised patients with HSV-related mucocutaneous infections that are refractory to therapy with acyclovir and/or foscarnet. [ABSTRACT FROM PUBLISHER]

Varicella is a common viral disease affecting almost the entire birth cohort. Although usually self-limiting, some cases of varicella can be serious, with 2 to 6% of cases attending a general practice resulting in complications. The hospitalisation rate for varicella in Europe ranges from 1.3 to 4.5 per 100,000 population/year and up to 10.1% of hospitalised patients report permanent or possible permanent sequelae (for example, scarring or ataxia). However, in many countries the epidemiology of varicella remains largely unknown or incomplete. In countries where routine childhood vaccination against varicella has been implemented, it has had a positive effect on disease prevention and control. Furthermore, mathematical models indicate that this intervention strategy may provide economic benefits for the individual and society. Despite this evidence and recommendations for varicella vaccination by official bodies such as the World Health Organization, and scientific experts in the field, the majority of European countries (with the exception of Germany and Greece) have delayed decisions on implementation of routine childhood varicella vaccination, choosing instead to vaccinate high-risk groups or not to vaccinate at all. In this paper, members of the Working Against Varicella in Europe group consider the practicalities of introducing routine childhood varicella vaccination in Europe, discussing the benefits and challenges of different vaccination options (vaccination vs. no vaccination, routine vaccination of infants vs. vaccination of susceptible adolescents or adults, two doses vs. one dose of varicella vaccine, monovalent varicella vaccines vs. tetravalent measles, mumps, rubella and varicella vaccines, as well as the optimal interval between two doses of measles, mumps, rubella and varicella vaccines). Assessment of the epidemiology of varicella in Europe and evidence for the effectiveness of varicella vaccination provides support for routine childhood programmes in Europe. Although European countries are faced with challenges or uncertainties that may have delayed implementation of a childhood vaccination programme, many of these concerns remain hypothetical and with new opportunities offered by combined measles, mumps, rubella and varicella vaccines, reassessment may be timely. [ABSTRACT FROM AUTHOR]

Varicella-zoster virus (VZV) encephalitis and meningitis are potential central nervous system (CNS) complications following primary VZV infection or reactivation. With Type-I interferon (IFN) signalling being an important first line cellular defence mechanism against VZV infection by the peripheral tissues, we here investigated the triggering of innate immune responses in a human neural-like environment. For this, we established and characterised 5-month matured hiPSC-derived neurospheroids (NSPHs) containing neurons and astrocytes. Subsequently, NSPHs were infected with reporter strains of VZV (VZV eGFP-ORF23 ) or Sendai virus (SeV eGFP ), with the latter serving as an immune-activating positive control. Live cell and immunocytochemical analyses demonstrated VZV eGFP-ORF23 infection throughout the NSPHs, while SeV eGFP infection was limited to the outer NSPH border. Next, NanoString digital transcriptomics revealed that SeV eGFP -infected NSPHs activated a clear Type-I IFN response, while this was not the case in VZV eGFP-ORF23 -infected NSPHs. Moreover, the latter displayed a strong suppression of genes related to IFN signalling and antigen presentation, as further demonstrated by suppression of IL-6 and CXCL10 production, failure to upregulate Type-I IFN activated anti-viral proteins (Mx1, IFIT2 and ISG15), as well as reduced expression of CD74, a key-protein in the MHC class II antigen presentation pathway. Finally, even though VZV eGFP-ORF23 -infection seems to be immunologically ignored in NSPHs, its presence does result in the formation of stress granules upon long-term infection, as well as disruption of cellular integrity within the infected NSPHs. Concluding, in this study we demonstrate that 5-month matured hiPSC-derived NSPHs display functional innate immune reactivity towards SeV infection, and have the capacity to recapitulate the strong immune evasive behaviour towards VZV., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Govaerts, Van Breedam, De Beuckeleer, Goethals, D’Incal, Di Stefano, Van Calster, Buyle-Huybrecht, Boeren, De Reu, Paludan, Thiry, Lebrun, Sadzot-Delvaux, Motaln, Rogelj, Van Weyenbergh, De Vos, Vanden Berghe, Ogunjimi, Delputte and Ponsaerts.)

Introduction: Although the treatment for pemphigus vulgaris (PV) has been revolutionized by the use of rituximab combined with corticosteroids, new effective therapies with a better safety profile are needed., Observation: A 67-year-old woman was diagnosed with severe mucosal PV, which was initially misdiagnosed as atypical Behçet's disease. Following an unsuccessful colchicine treatment, significant improvement was observed upon the introduction of apremilast: reduced pain, fewer lesions, and a stabilized weight. The discontinuation of apremilast led to a rapid relapse. Retrospective analysis through anti-Dsg3 ELISA indicated a gradual decrease in antibody levels during the apremilast treatment., Discussion: Apremilast, a phosphodiesterase 4 inhibitor approved for psoriasis and Behçet's disease's related oral ulcers treatment, demonstrated its efficacy in this PV case. This is the second case report highlighting the effectiveness of apremilast for PV treatment. Apremilast's ability to upregulate cyclic adenosine monophosphate (cAMP) levels appears to contribute to the stabilization of keratinocyte adhesion., Conclusion: Apremilast may be a promising therapeutic option for the treatment of pemphigus, with an innovative mechanism of action, no induced immunosuppression, and good tolerance. It could be a good alternative to steroids, in the treatment regimen of steroids combined with rituximab., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Delvaux, Bohelay, Sitbon, Soued, Alexandre, Cucherousset, Gilardin, Diep, Caux and Le Roux-Villet.)

A recently developed proteolytic reactor, designed for protein structural investigation, was coupled to ion mobility mass spectrometry to monitor collisional cross section (CCS) evolution of model proteins undergoing trypsin-mediated mono enzymatic digestion. As peptides are released during digestion, the CCS of the remaining protein structure may deviate from the classical 2/3 power of the CCS-mass relationship for spherical structures. The classical relationship between CCS and mass (CCS = A × M 2/3 ) for spherical structures, assuming a globular shape in the gas phase, may deviate as stabilizing elements are lost during digestion. In addition, collision-induced unfolding (CIU) experiments on partially digested proteins provided insights into the CCS resilience in the gas phase to ion activation, potentially due to the presence of stabilizing elements. The study initially investigated a model peptide ModBea (3 kDa), assessing the impact of disulfide bridges on CCS resilience in both reduced and oxidized forms. Subsequently, β-lactoglobulin (2 disulfide bridges), calmodulin (Ca 2+ coordination cation), and cytochrome c (heme) were selected to investigate the influence of common structuring elements on CCS resilience. CIU experiments probed the unfolding process, evaluating the effect of losing specific peptides on the energy landscapes of partially digested proteins. Comparisons of the TW CCS N2→He to trend curves describing the CCS/mass relationship revealed that proteins with structure-stabilizing elements consistently exhibit TW CCS N2→He and greater resilience toward CIU compared to proteins lacking these elements. The integration of online digestion, ion mobility, and CIU provides a valuable tool for identifying structuring elements in biopolymers in the gas phase.

In the tropics, more precisely in equatorial dense rainforest, xylogenesis is driven by a little distinct climatological seasonality, and many tropical trees do not show clear growth rings. This makes retrospective analyses and modeling of future tree performance difficult. This research investigates the presence, the distinctness, and the periodicity of growth ring for dominant tree species in two semi-deciduous rainforests, which contrast in terms of precipitation dynamics. Eighteen tree species common to both forests were investigated. We used the cambial marking technique and then verified the presence and periodicity of growth-ring boundaries in the wood produced between pinning and collection by microscopic and macroscopic observation. The study showed that all eighteen species can form visible growth rings in both sites. However, the periodicity of ring formation varied significantly within and between species, and within sites. Trees from the site with clearly defined dry season had a higher likelihood to form periodical growth rings compared to those from the site where rainfall seasonality is less pronounced. The distinctness of the formed rings however did not show a site dependency. Periodical growth-ring formation was more likely in fast-growing trees. Furthermore, improvements can be made by a detailed study of the cambial activity through microcores taken at high temporal resolution, to get insight on the phenology of the lateral meristem., Competing Interests: The authors declare that the research was conducted in the absence of any conflict of interest., (© 2024 The Author(s). Plant‐Environment Interactions published by New Phytologist Foundation and John Wiley & Sons Ltd.)

Background and Purpose: Deep inspiration breath-hold (DIBH) protects critical organs-at-risk (OARs) for adjuvant breast radiotherapy. Guidance systems e.g. surface guided radiation therapy (SGRT) improve the positional breast reproducibility and stability during DIBH. In parallel, OARs sparing with DIBH is enhanced through different techniques e.g. prone position, continuous positive airway pressure (CPAP). By inducing repeated DIBH with the same level of positive pressure, mechanically-assisted and non-invasive ventilation (MANIV) could potentially combine these DIBH optimizations., Materials and Methods: We conducted a randomized, open-label, multicenter and single-institution non-inferiority trial. Sixty-six patients eligible for adjuvant left whole-breast radiotherapy in supine position were equally assigned between mechanically-induced DIBH (MANIV-DIBH) and voluntary DIBH guided by SGRT (sDIBH). The co-primary endpoints were positional breast stability and reproducibility with a non-inferiority margin of 1 mm. Secondary endpoints were tolerance assessed daily via validated scales, treatment time, dose to OARs and their inter-fraction positional reproducibility., Results: Differences between both arms for positional breast reproducibility and stability occurred at a sub-millimetric level (p < 0.001 for non-inferiority). The left anterior descending artery near-max dose (14,6 ± 12,0 Gy vs. 7,7 ± 7,1 Gy, p = 0,018) and mean dose (5,0 ± 3,5 Gy vs. 3,0 ± 2,0 Gy, p = 0,009) were improved with MANIV-DIBH. The same applied for the V 5Gy of the left ventricle (2,4 ± 4,1 % vs. 0,8 ± 1,6 %, p = 0,001) as well as for the left lung V 20Gy (11,4 ± 2,8 % vs. 9,7 ± 2,7 %, p = 0,019) and V 30Gy (8,0 ± 2,6 % vs. 6,5 ± 2,3 %, p = 0,0018). Better heart's inter-fraction positional reproducibility was observed with MANIV-DIBH. Tolerance and treatment time were similar., Conclusion: Mechanical ventilation provides the same target irradiation accuracy as with SGRT while better protecting and repositioning OARs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

With Varicella-Zoster Virus (VZV) being an exclusive human pathogen, human induced pluripotent stem cell (hiPSC)-derived neural cell culture models are an emerging tool to investigate VZV neuro-immune interactions. Using a compartmentalized hiPSC-derived neuronal model allowing axonal VZV infection, we previously demonstrated that paracrine interferon (IFN)-α2 signalling is required to activate a broad spectrum of interferon-stimulated genes able to counteract a productive VZV infection in hiPSC-neurons. In this new study, we now investigated whether innate immune signalling by VZV-challenged macrophages was able to orchestrate an antiviral immune response in VZV-infected hiPSC-neurons. In order to establish an isogenic hiPSC-neuron/hiPSC-macrophage co-culture model, hiPSC-macrophages were generated and characterised for phenotype, gene expression, cytokine production and phagocytic capacity. Even though immunological competence of hiPSC-macrophages was shown following stimulation with the poly(dA:dT) or treatment with IFN-α2, hiPSC-macrophages in co-culture with VZV-infected hiPSC-neurons were unable to mount an antiviral immune response capable of suppressing a productive neuronal VZV infection. Subsequently, a comprehensive RNA-Seq analysis confirmed the lack of strong immune responsiveness by hiPSC-neurons and hiPSC-macrophages upon, respectively, VZV infection or challenge. This may suggest the need of other cell types, like T-cells or other innate immune cells, to (co-)orchestrate an efficient antiviral immune response against VZV-infected neurons., Competing Interests: CM, PR and MA-R are affiliated with the Centre for Genomics and Oncological Research (GENYO), Pfizer-University of Granada-Junta de Andalucía, whereby Pfizer is solely the owner of the build-ing and provides funding for maintenance of the building. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Van Breedam, Buyle-Huybrecht, Govaerts, Meysman, Bours, Boeren, Di Stefano, Caers, De Reu, Dirkx, Schippers, Bartholomeus, Lebrun, Sadzot-Delvaux, Rybakowska, Alarcón-Riquelme, Marañón, Laukens, Delputte, Ogunjimi and Ponsaerts.)

Varicella-zoster virus (VZV) infection of neuronal cells and the activation of cell-intrinsic antiviral responses upon infection are still poorly understood mainly due to the scarcity of suitable human in vitro models that are available to study VZV. We developed a compartmentalized human-induced pluripotent stem cell (hiPSC)-derived neuronal culture model that allows axonal VZV infection of the neurons, thereby mimicking the natural route of infection. Using this model, we showed that hiPSC-neurons do not mount an effective interferon-mediated antiviral response following VZV infection. Indeed, in contrast to infection with Sendai virus, VZV infection of the hiPSC-neurons does not result in the upregulation of interferon-stimulated genes (ISGs) that have direct antiviral functions. Furthermore, the hiPSC-neurons do not produce interferon-α (IFNα), a major cytokine that is involved in the innate antiviral response, even upon its stimulation with strong synthetic inducers. In contrast, we showed that exogenous IFNα effectively limits VZV spread in the neuronal cell body compartment and demonstrated that ISGs are efficiently upregulated in these VZV-infected neuronal cultures that are treated with IFNα. Thus, whereas the cultured hiPSC neurons seem to be poor IFNα producers, they are good IFNα responders. This could suggest an important role for other cells such as satellite glial cells or macrophages to produce IFNα for VZV infection control.

Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, which remains difficult to cure. The very high recurrence rate has been partly attributed to the presence of GBM stem-like cells (GSCs) within the tumors, which have been associated with elevated chemokine receptor 4 (CXCR4) expression. CXCR4 is frequently overexpressed in cancer tissues, including GBM, and usually correlates with a poor prognosis. We have created a CXCR4-retargeted oncolytic herpesvirus (oHSV) by insertion of an anti-human CXCR4 nanobody in glycoprotein D of an attenuated HSV-1 (ΔICP34.5, ΔICP6, and ΔICP47), thereby describing a proof of principle for the use of nanobodies to target oHSVs toward specific cellular entities. Moreover, this virus has been armed with a transgene expressing a soluble form of TRAIL to trigger apoptosis. In vitro , this oHSV infects U87MG CXCR4 + and patient-derived GSCs in a CXCR4-dependent manner and, when armed, triggers apoptosis. In a U87MG CXCR4 + orthotopic xenograft mouse model, this oHSV slows down tumor growth and significantly improves mice survival. Customizing oHSVs with diverse nanobodies for targeting multiple proteins appears as an interesting approach for tackling the heterogeneity of GBM, especially GSCs. Altogether, our study must be considered as a proof of principle and a first step toward personalized GBM virotherapies to complement current treatments., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

For decades, structural analysis of proteins have received considerable attention, from their sequencing to the determination of their 3D structures either in the free state (e.g., no host-guest system, apoproteins) or (non)covalently bound complexes. The elucidation of the 3D structures and the mapping of intra- and intermolecular interactions are valuable sources of information to understand the physicochemical properties of such systems. X-ray crystallography and nuclear magnetic resonance are methods of choice for obtaining structures at the atomic level. Nonetheless, they still present drawbacks which limit their use to highly purified systems in a relatively high amount. On the contrary, mass spectrometry (MS) has become a powerful tool thanks to its selectivity, sensitivity, and the development of structural methods both at the global shape and the residue level. The combination of several MS-based methods is mandatory to fully assign a putative structure in combination with computational chemistry and bioinformatics. In that context, we propose a strategy which complements the existing methods of structural studies (e.g., circular dichroism, hydrogen/deuterium exchange and cross-links experiments, nuclear magnetic resonance). The workflow is based on the collection of structural information on proteins from the apparition rates and the time of appearance of released peptides generated by a protease in controlled experimental conditions with online detection by electrospray high-resolution mass spectrometry. Nondenaturing, partially or fully denatured proteins were digested by the enzymatic reactor, i.e., β-lactoglobulin, cytochrome c , and β-casein. The collected data are interpreted with regard to the kinetic schemes with time-dependent rates of the enzymatic digestion established beforehand, considering kinetics parameters in the Michaelis-Menten formalism including k cat (the turnover number), k 1 (formation of the enzyme-substrate complex), k -1 (dissociation of the enzyme-substrate complex), k off (local refolding of the protein around the cleavage site), and k on (local unfolding of the protein around the cleavage site). Solvent-accessible surface analysis through digestion kinetics was also investigated. The initial apparition rates of released peptides varied according to the protein state (folded vs denatured) and informs the k off / k on ratio around the cleavage site. On the other hand, the time of appearance of a given peptide is related to its solvent accessibility and to the resilience of the residual protein structure in solution. Temperature-dependent digestion experiments allowed estimation of the type of secondary structures around the cleavage site.