Explosive cell lysis as a mechanism for the biogenesis of bacterial membrane vesicles and biofilms

Many bacteria produce extracellular and surface-associated components such as membrane vesicles (MVs), extracellular DNA and moonlighting cytosolic proteins for which the biogenesis and export pathways are not fully understood. Here we show that the explosive cell lysis of a sub-population of cells accounts for the liberation of cytosolic content in Pseudomonas aeruginosa biofilms. Super-resolution microscopy reveals that explosive cell lysis also produces shattered membrane fragments that rapidly form MVs. A prophage endolysin encoded within the R- and F-pyocin gene cluster is essential for explosive cell lysis. Endolysin-deficient mutants are defective in MV production and biofilm development, consistent with a crucial role in the biogenesis of MVs and liberation of extracellular DNA and other biofilm matrix components. Our findings reveal that explosive cell lysis, mediated through the activity of a cryptic prophage endolysin, acts as a mechanism for the production of bacterial MVs

5-fluorouracil modulated by leucovorin, methotrexate and mitomycin: highly effective, low-cost chemotherapy for advanced colorectal cancer

We have reported that an alternating regimen of bolus and continuous infusion 5-fluorouracil (FU) was superior to bolus FU in terms of response rate and progression-free survival in advanced colorectal cancer. Biochemical modulation was an essential part of this regimen and it was selective for the schedule of FU administration: bolus FU was in fact modulated by methotrexate (MTX) while continuous infusion FU was potentiated by 6-s-leucovorin (LV). Considering the low cost and the favourable report on the activity of mitomycin C (mito) added to CI FU, we have incorporated this agent in the infusional part of our treatment programme. 105 patients with untreated, advanced, measurable colorectal cancer were accrued from 13 Italian centres and treated with the following regimen. 2 biweekly cycles of FU bolus (600 mg/m2), modulated by MTX (24 h earlier, 200 mg/m2) were alternated with a 3-week continuous infusion of FU (200 mg/m2daily), modulated by LV (20 mg/m2weekly bolus). Mito, 7 mg/m2, was given on the first day of the infusional period. After a 1 week rest, the whole cycle (8 weeks) was repeated, if indicated. 5 complete and 34 partial responses were obtained (response rate, 37% on the intention to treat basis; 95% confidence limits, 28–46%). After a median follow-up time of 26 months, 37 patients are still alive. The median progression-free survival is 7.7 months with an overall survival of 18.8 months and a 2-year survival rate of 30%. The regimen was very well tolerated with fewer than 13% of patients experiencing WHO grade III–IV toxicity. These results are consistent with those obtained by our group in 3 previous trials of schedule specific biochemical modulation of FU. They also indicate a highly active, little toxic, inexpensive regimen of old drugs to be used (a) as an alternative to the more expensive combinations including CPT-11 or oxaliplatin or (b) as the basis for combination programmes with these agents. © 2001 Cancer Research Campaign http://www.bjcancer.co

Social and cultural origins of motivations to volunteer a comparison of university students in six countries

Although participation in volunteering and motivations to volunteer (MTV) have received substantial attention on the national level, particularly in the US, few studies have compared and explained these issues across cultural and political contexts. This study compares how two theoretical perspectives, social origins theory and signalling theory, explain variations in MTV across different countries. The study analyses responses from a sample of 5794 students from six countries representing distinct institutional contexts. The findings provide strong support for signalling theory but less so for social origins theory. The article concludes that volunteering is a personal decision and thus is influenced more at the individual level but is also impacted to some degree by macro-level societal forces

Type II supernovae from the Carnegie Supernova Project-I. I. Bolometric light curves of 74 SNe II using uBgVriYJH photometry

The present study is the first of a series of three papers where we characterise the type II supernovae (SNe~II) from the Carnegie Supernova Project-I to understand their diversity in terms of progenitor and explosion properties. In this first paper, we present bolometric light curves of 74 SNe~II. We outline our methodology to calculate the bolometric luminosity, which consists of the integration of the observed fluxes in numerous photometric bands ($uBgVriYJH$) and black-body (BB) extrapolations to account for the unobserved flux at shorter and longer wavelengths. BB fits were performed using all available broadband data except when line blanketing effects appeared. Photometric bands bluer than $r$ that are affected by line blanketing were removed from the fit, which makes near-infrared (NIR) observations highly important to estimate reliable BB extrapolations to the infrared. BB fits without NIR data produce notably different bolometric light curves, and therefore different estimates of SN~II progenitor and explosion properties when data are modelled. We present two methods to address the absence of NIR observations: (a) colour-colour relationships from which NIR magnitudes can be estimated using optical colours, and (b) new prescriptions for bolometric corrections as a function of observed SN~II colours. Using our 74 SN~II bolometric light curves, we provide a full characterisation of their properties based on several observed parameters. We measured magnitudes at different epochs, as well as durations and decline rates of different phases of the evolution. An analysis of the light-curve parameter distributions was performed, finding a wide range and a continuous sequence of observed parameters which is consistent with previous analyses using optical light curves.Comment: Accepted for publication in A&

Type II supernovae from the Carnegie Supernova Project-I. II. Physical parameter distributions from hydrodynamical modelling

Linking supernovae to their progenitors is a powerful method for furthering our understanding of the physical origin of their observed differences, while at the same time testing stellar evolution theory. In this second study of a series of three papers where we characterise SNe II to understand their diversity, we derive progenitor properties (initial and ejecta masses, and radius), explosion energy, $^{56}$Ni mass, and its degree of mixing within the ejecta for a large sample of SNe II. This dataset was obtained by the Carnegie Supernova Project-I and is characterised by a high cadence of their optical and NIR light curves and optical spectra that were homogeneously observed and processed. A large grid of hydrodynamical models and a fitting procedure based on MCMC methods were used to fit the bolometric light curve and the evolution of the photospheric velocity of 53 SNe II. We infer ejecta masses between 7.9 and 14.8 $M_{\odot}$, explosion energies between 0.15 and 1.40 foe, and $^{56}$Ni masses between 0.006 and 0.069 $M_{\odot}$. We define a subset of 24~SNe (the `gold sample') with well-sampled bolometric light curves and expansion velocities for which we consider the results more robust. Most SNe~II in the gold sample ($\sim$88%) are found with ejecta masses in the range of $\sim$8-10 $M_{\odot}$, coming from low zero-age main-sequence masses (9-12 $M_{\odot}$). The modelling of the initial-mass distribution of the gold sample gives an upper mass limit of 21.3$^{+3.8}_{-0.4}$ $M_{\odot}$ and a much steeper distribution than that for a Salpeter massive-star IMF. This IMF incompatibility is due to the large number of low-mass progenitors found -- when assuming standard stellar evolution. This may imply that high-mass progenitors lose more mass during their lives than predicted. However, a deeper analysis of all stellar evolution assumptions is required to test this hypothesis.Comment: Accepted for publication in Astronomy & Astrophysic

Type II supernovae from the Carnegie Supernova Project-I: I. Bolometric light curves of 74 SNe II using uBgVriYJH photometry

The present study is the first of a series of three papers where we characterise the type II supernovae (SNe II) from the Carnegie Supernova Project-I to understand their diversity in terms of progenitor and explosion properties. In this first paper, we present bolometric light curves of 74 SNe II. We outline our methodology to calculate the bolometric luminosity, which consists of the integration of the observed fluxes in numerous photometric bands (uBgVriYJH) and black-body (BB) extrapolations to account for the unobserved flux at shorter and longer wavelengths. BB fits were performed using all available broadband data except when line blanketing effects appeared. Photometric bands bluer than r that are affected by line blanketing were removed from the fit, which makes near-infrared (NIR) observations highly important to estimate reliable BB extrapolations to the infrared. BB fits without NIR data produce notably different bolometric light curves, and therefore different estimates of SN II progenitor and explosion properties when data are modelled. We present two methods to address the absence of NIR observations: (a) colour-colour relationships from which NIR magnitudes can be estimated using optical colours, and (b) new prescriptions for bolometric corrections as a function of observed SN II colours. Using our 74 SN II bolometric light curves, we provide a full characterisation of their properties based on several observed parameters. We measured magnitudes at different epochs, as well as durations and decline rates of different phases of the evolution. An analysis of the light-curve parameter distributions was performed, finding a wide range and a continuous sequence of observed parameters which is consistent with previous analyses using optical light curves.The work of the Carnegie Supernova Project was supported by the National Science Foundation under grants AST-0306969, AST-0607438, AST-1008343, AST-1613426, AST-1613472, and AST-1613455. L. M. acknowledges support from a CONICET fellowship. L. M. and M. O. acknowledge support from UNRN PI2018 40B885 grant. M. H. acknowledges support from the Hagler Institute of Advanced Study at Texas A&M University. S. G. G. acknowledges support by FCT under Project CRISP PTDC/FIS-AST-31546/2017 and Project No. UIDB/00099/2020. M. S. is supported by grants from the VILLUM FONDEN (grant number 28021) and the Independent Research Fund Denmark (IRFD; 8021-00170B). F. F. acknowledges support from the National Agency for Research and Development (ANID) grants: BASAL Center of Mathematical Modelling AFB-170001, Ministry of Economy, Development, and Tourism’s Millennium Science Initiative through grant IC12009, awarded to the Millennium Institute of Astrophysics, and FONDECYT Regular #1200710. L. G. acknowledges financial support from the Spanish Ministry of Science, Innovation and Universities (MICIU) under the 2019 Ramón y Cajal program RYC2019-027683 and from the Spanish MICIU project PID2020-115253GA-I00. P.H. acknowledges the support by National Science Foundation (NSF) grant AST-1715133

A combination of gemcitabine and 5-fluorouracil in advanced pancreatic cancer, a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD)

In a randomized clinical trial, gemcitabine (GEM) was more effective than 5-fluorouracil (5-FU) in advanced pancreatic cancer patients. GEM and 5-FU have different mechanisms of action and their combination, from a theoretical point of view, could result in a higher activity. To test activity and feasibility of such a combination, a multi-institutional phase II study was initiated in November 1996 by the Italian Group for the study of Digestive Tract Cancer (GISCAD). Primary objectives of this study were to determine the activity in terms of response rate and clinical benefit, while the secondary objective was toxicity. According to the optimal two-stage phase II design, 54 patients were enrolled. Schedule was: GEM 1000 mg m(-2) intravenous (i.v.), and 5-FU 600 mg m(-2) bolus i.v. weekly for 3 weeks out of every 4. All the 54 patients were symptomatic (pain, weight loss, dyspepsia). A clinical benefit was obtained in 28 patients (51\%) (95\% confidence interval (CI) 38-64\%). Two patients achieved a partial response and 34 a stable disease. Median survival for all the patients was 7 months. Side-effects were mild: no gastrointestinal or haematological grade 3-4 toxicity (WHO) were recorded. We observed only six episodes of grade 2 (WHO) leukopenia and seven episodes of thrombocytopenia. Although the non-randomized design of this study suggests caution in the interpretation of these data, in consideration of the low incidence of toxicity and the favourable results obtained in terms of clinical benefit, it may be worthwhile to test more active schedules of 5-FU (continuous infusion) in combination with gemcitabine

Broad-emission-line dominated hydrogen-rich luminous supernovae

Hydrogen-rich Type II supernovae (SNe II) are the most frequently observed class of core-collapse SNe (CCSNe). However, most studies that analyse large samples of SNe II lack events with absolute peak magnitudes brighter than -18.5 mag at rest-frame optical wavelengths. Thanks to modern surveys, the detected number of such luminous SNe II (LSNe II) is growing. There exist several mechanisms that could produce luminous SNe II. The most popular propose either the presence of a central engine (a magnetar gradually spinning down or a black hole accreting fallback material) or the interaction of supernova ejecta with circumstellar material (CSM) that turns kinetic energy into radiation energy. In this work, we study the light curves and spectral series of a small sample of six LSNe II that show peculiarities in their H$\alpha$ profile, to attempt to understand the underlying powering mechanism. We favour an interaction scenario with CSM that is not dense enough to be optically thick to electron scattering on large scales -- thus, no narrow emission lines are observed. This conclusion is based on the observed light curve (higher luminosity, fast decline, blue colours) and spectral features (lack of persistent narrow lines, broad H$\alpha$ emission, lack of H$\alpha$ absorption, weak or nonexistent metal lines) together with comparison to other luminous events available in the literature. We add to the growing evidence that transients powered by ejecta-CSM interaction do not necessarily display persistent narrow emission lines.Comment: 27 pages, 16 figures, accepted for publication in MNRA

SN 2020zbf: A fast-rising hydrogen-poor superluminous supernova with strong carbon lines

SN 2020zbf is a hydrogen-poor superluminous supernova at $z = 0.1947$ that shows conspicuous C II features at early times, in contrast to the majority of H-poor SLSNe. Its peak magnitude is $M_{\rm g}$ = $-21.2$ mag and its rise time ($\lesssim 24$ days from first light) place SN 2020zbf among the fastest rising SLSNe-I. Spectra taken from ultraviolet (UV) to near-infrared wavelengths are used for the identification of spectral features. We pay particular attention to the C II lines as they present distinctive characteristics when compared to other events. We also analyze UV and optical photometric data, and model the light curves considering three different powering mechanisms: radioactive decay of Ni, magnetar spin-down and circumstellar material interaction (CSM). The spectra of SN 2020zbf match well with the model spectra of a C-rich low-mass magnetar model. This is consistent with our light curve modelling which supports a magnetar-powered explosion with a $M_{\rm ej}$ = 1.5 $M_\odot$. However, we cannot discard the CSM-interaction model as it also may reproduce the observed features. The interaction with H-poor, carbon-oxygen CSM near peak could explain the presence of C II emission lines. A short plateau in the light curve, around 30 - 40 days after peak, in combination with the presence of an emission line at 6580 \r{A} can also be interpreted as late interaction with an extended H-rich CSM. Both the magnetar and CSM interaction models of SN 2020zbf indicate that the progenitor mass at the time of explosion is between 2 - 5 $M_\odot$. Modelling the spectral energy distribution of the host reveals a host mass of 10$^{8.7}$ $M_\odot$, a star-formation rate of 0.24$^{+0.41}_{-0.12}$ $M_\odot$ yr$^{-1}$ and a metallicity of $\sim$ 0.4 $Z_\odot$.Comment: 26 pages, 22 figures, submitted to A&

Soybean Seed Extracts Preferentially Express Genomic Loci of Bradyrhizobium japonicum in the Initial Interaction with Soybean, Glycine max (L.) Merr

Initial interaction between rhizobia and legumes actually starts via encounters of both partners in the rhizosphere. In this study, the global expression profiles of Bradyrhizobium japonicum USDA 110 in response to soybean (Glycine max) seed extracts (SSE) and genistein, a major soybean-released isoflavone for nod genes induction of B. japonicum, were compared. SSE induced many genomic loci as compared with genistein (5.0 µM), nevertheless SSE-supplemented medium contained 4.7 µM genistein. SSE markedly induced four predominant genomic regions within a large symbiosis island (681 kb), which include tts genes (type III secretion system) and various nod genes. In addition, SSE-treated cells expressed many genomic loci containing genes for polygalacturonase (cell-wall degradation), exopolysaccharide synthesis, 1-aminocyclopropane-1-carboxylate deaminase, ribosome proteins family and energy metabolism even outside symbiosis island. On the other hand, genistein-treated cells exclusively showed one expression cluster including common nod gene operon within symbiosis island and six expression loci including multidrug resistance, which were shared with SSE-treated cells. Twelve putatively regulated genes were indeed validated by quantitative RT-PCR. Several SSE-induced genomic loci likely participate in the initial interaction with legumes. Thus, these results can provide a basic knowledge for screening novel genes relevant to the B. japonicum- soybean symbiosis