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Bacterial quorum sensing molecules not only grant the communication within bacterial communities, but also influence eukaryotic hosts. N-acyl-homoserine lactones (AHLs) produced by pathogenic or beneficial bacteria were shown to induce diverse reactions in animals and plants. In plants, the reaction to AHLs depends on the length of the lipid side chain. Here we investigated the impact of two bacteria on Arabidopsis thaliana, which usually enter a close symbiosis with plants from the Fabaceae (legumes) family and produce a long-chain AHL (Sinorhizobium meliloti) or a short-chain AHL (Rhizobium etli). We demonstrate that, similarly to the reaction to pure AHL molecules, the impact, which the inoculation with rhizosphere bacteria has on plants, depends on the type of the produced AHL. The inoculation with oxo-C14-HSL-producing S. meliloti strains enhanced plant resistance towards pathogenic bacteria, whereas the inoculation with an AttM lactonase-expressing S. meliloti strain did not. Inoculation with the oxo-C8-HSL-producing R. etli had no impact on the resistance, which is in agreement with our previous hypothesis. In addition, plants seem to influence the availability of AHLs in the rhizosphere. Taken together, this report provides new insights in the role of N-acyl-homoserine lactones in the inter-kingdom communication at the root surface.

Invasive species that proliferate after colonizing new habitats have a negative environmental and economic impact. The reason why some species become successful invaders, whereas others, even closely related species, remain noninvasive is often unclear. The harlequin ladybird Harmonia axyridis, introduced for biological pest control, has become an invader that is outcompeting indigenous ladybird species in many countries. Here, we show that Harmonia carries abundant spores of obligate parasitic microsporidia closely related to Nosema thompsoni. These microsporidia, while not harming the carrier Harmonia, are lethal pathogens for the native ladybird Coccinella septempunctata. We propose that intraguild predation, representing a major selective force among competing ladybird species, causes the infection and ultimate death of native ladybirds when they feed on microsporidia-contaminated Harmonia eggs or larvae.

Approximately 950 individual sequences of non-ribosomally biosynthesised peptides are produced by the genus Trichoderma / Hypocrea that belong to a perpetually growing class of mostly linear antibiotic oligopeptides, which are rich in the non-proteinogenic α -aminoisobutyric acid (Aib). Thus, they are comprehensively named peptaibiotics. Notably, peptaibiotics represent ca. 80 % of the total inventory of secondary metabolites currently known from Trichoderma/Hypocrea . Their unique membrane-modifying bioactivity results from amphipathicity and helicity, thus making them ideal candidates in assisting both colonisation and defence of the natural habitats by their fungal producers. Despite this, reports on the in vivo-detection of peptaibiotics have scarcely been published in the past. In order to evaluate the significance of peptaibiotic production for a broader range of potential producers, we screened nine specimens belonging to seven hitherto uninvestigated fungicolous or saprotrophic Trichoderma/Hypocrea species by liquid chromatography coupled to electrospray high resolution mass spectrometry. Sequences of peptaibiotics found were independently confirmed by analysing the peptaibiome of pure agar cultures obtained by single-ascospore isolation from the specimens. Of the nine species examined, five were screened positive for peptaibiotics. A total of 78 peptaibiotics were sequenced, 56 (= 72 %) of which are new. Notably, dihydroxyphenylalaninol and O -prenylated tyrosinol, two C -terminal residues, which have not been reported for peptaibiotics before, were found as well as new and recurrent sequences carrying the recently described tyrosinol residue at their C -terminus. The majority of peptaibiotics sequenced are 18- or 19-residue peptaibols. Structural homologies with ‘classical representatives’ of subfamily 1 (SF1)-peptaibiotics argue for the formation of transmembrane ion channels, which are prone to facilitate the producer capture and defence of its substratum.

Comments by de Jong et al ., Solter et al ., and Sloggett question the ecological relevance of the abundant microsporidia found in the invasive ladybird Harmonia axyridis . We contend that there is abundant evidence that native ladybirds feed on H. axyridis eggs and that interspecific microsporidial transfer is a common phenomenon, supporting the proposed role of these parasites as biological weapons.

Comments by de Jong et al ., Solter et al ., and Sloggett question the ecological relevance of the abundant microsporidia found in the invasive ladybird Harmonia axyridis . We contend that there is abundant evidence that native ladybirds feed on H. axyridis eggs and that interspecific microsporidial transfer is a common phenomenon, supporting the proposed role of these parasites as biological weapons.

Spinal cord injury results in permanent neurological impairment and disability due to the absence of spontaneous regeneration. NG101, a recombinant human antibody, neutralises the neurite growth-inhibiting protein Nogo-A, promoting neural repair and motor recovery in animal models of spinal cord injury. We aimed to evaluate the efficacy of intrathecal NG101 on recovery in patients with acute cervical traumatic spinal cord injury. This randomised, double-blind, placebo-controlled phase 2b clinical trial was done at 13 hospitals in the Czech Republic, Germany, Spain, and Switzerland. Patients aged 18–70 years with acute, complete or incomplete cervical spinal cord injury (neurological level of injury C1–C8) within 4–28 days of injury were eligible for inclusion. Participants were initially randomly assigned 1:1 to intrathecal treatment with 45 mg NG101 or placebo (phosphate-buffered saline); 18 months into the study, the ratio was adjusted to 3:1 to achieve a final distribution of 2:1 to improve enrolment and drug exposure. Randomisation was done using a centralised, computer-based randomisation system and was stratified according to nine distinct outcome categories with a validated upper extremity motor score (UEMS) prediction model based on clinical parameters at screening. Six intrathecal injections were administered every 5 days over 4 weeks, starting within 28 days of injury. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was change in UEMS at 6 months, analysed alongside safety in the full analysis set. The completed trial was registered at ClinicalTrials.gov, NCT03935321. From May 20, 2019, to July 20, 2022, 463 patients with acute traumatic cervical spinal cord injury were screened, 334 were deemed ineligible and excluded, and 129 were randomly assigned to an intervention (80 patients in the NG101 group and 49 in the placebo group). The full analysis set comprised 78 patients from the NG101 group and 48 patients from the placebo group. 107 (85%) patients were male and 19 (15%) patients were female, with a median age of 51·5 years (IQR 30·0–60·0). Across all patients, the primary endpoint showed no significant difference between groups (with UEMS change at 6 months 1·37 [95% CI –1·44 to 4·18]; placebo group mean 19·20 [SD 11·78] at baseline and 30·91 [SD 15·49] at day 168; NG101 group mean 18·23 [SD 15·14] at baseline and 31·31 [19·54] at day 168). Treatment-related adverse events were similar between groups (nine in the NG101 group and six in the placebo group). 25 severe adverse events were reported: 18 in 11 (14%) patients in the NG101 group and seven in six (13%) patients in the placebo group. Although no treatment-related fatalities were reported in the NG101 group, one fatality not related to treatment occurred in the placebo group. Infections were the most common adverse event affecting 44 (92%) patients in the placebo group and 65 (83%) patients in the NG101 group. NG101 did not improve UEMS in patients with acute spinal cord injury. Post-hoc subgroup analyses assessing UEMS and Spinal Cord Independence Measure of self-care in patients with motor-incomplete injury indicated potential beneficial effects that require investigation in future studies. EU program Horizon2020; Swiss State Secretariat for Education, Research and Innovation; Wings for Life; the Swiss Paraplegic Foundation; and the CeNeReg project of Wyss Zurich (University of Zurich and Eidgenössische Technische Hochschule Zurich).

This paper presents the measurement of the isolated prompt photon inclusive production cross section in pp and p–Pb collisions by the ALICE Collaboration at the LHC. The measurement is performed in p–Pb collisions at centre-of-mass energies per nucleon pair of s NN = 5.02 TeV and 8.16 TeV, as well as in pp collisions at s = 5.02 TeV and 8 TeV. The cross section is obtained at midrapidity ( | y | < 0.7 ) using a charged-track based isolation momentum p T iso, ch < 1.5 GeV / c in a cone with radius R = 0.4 . The data for both collision systems are well reproduced by perturbative QCD (pQCD) calculations at next-to-leading order (NLO) using recent parton distribution functions for free (PDF) and bound (nPDF) nucleons. Furthermore, the nuclear modification factor R pA for both collision energies is consistent with unity for p T > 20 GeV / c . However, deviations from unity ( R pA < 1 ) of up to 20% are observed for p T < 20 GeV / c with limited significance, indicating the possible presence of nuclear effects in the initial state of the collision. The suppression increases with decreasing p T with a significance of 2.3 σ for a non-zero slope and yields R pA < 1 with a significance of 1.8 σ at s NN = 8.16 TeV for p T < 20 GeV / c . In addition, a significance of 1.1 σ is observed for R pA < 1 at the lower collision energy s NN = 5.02 TeV for p T < 14 GeV / c . The magnitude and shape of the suppression are consistent with pQCD predictions at NLO using nPDFs that incorporate nuclear shadowing effects in the Pb nucleus.

Differential cross sections of charged particles in inelastic pp collisions as a function of p T have been measured at at the LHC. The p T spectra are compared to NLO-pQCD calculations. Though the differential cross section for an individual cannot be described by NLO-pQCD, the relative increase of cross section with is in agreement with NLO-pQCD. Based on these measurements and observations, procedures are discussed to construct pp reference spectra at up to p T =50 GeV/ c as required for the calculation of the nuclear modification factor in nucleus–nucleus and proton–nucleus collisions.

Activation of the Raf/MEK/ERK (MAPK) signal transduction cascade by RAS mutations has been found in a variety of human cancers. Mutations of BRAF provide an alternative route for activation of this signalling pathway. To determine the role of mutations in BRAF and KRAS2 in the neoplastic progression of Barrett's adenocarcinoma, we analysed both genes for common mutations. After microdissection, DNA of 19 Barrett's adenocarcinomas, 56 Barrett's intraepithelial neoplasias ( n =29 low-grade intraepithelial neoplasia (LGIN) and n =27 high-grade intraepithelial neoplasia (HGIN)), 30 Barrett's mucosa without neoplasia and normal squamous, as well as gastric epithelium, were analysed for BRAF and KRAS2 mutation. Activating BRAF mutations were identified in 2/19 Barrett's adenocarcinomas (11%) and in 1/27 HGIN (4%). KRAS2 mutations were found in four out of 19 (21%) Barrett's adenocarcinomas examined and in three cases of HGIN (11%). In LGIN as well as in normal gastric or oesophageal mucosa, neither BRAF nor KRAS2 mutations were detected. All lesions with KRAS2 mutations had an intact BRAF gene. The status of mismatch-repair proteins was neither related to BRAF nor KRAS2 mutations. These data indicate that RAS or BRAF mutations are detected in about 32% of all Barrett's adenocarcinomas. We conclude that the disruption of the Raf/MEK/ERK (MAPK) kinase pathway is a frequent but also early event in the development of Barrett's adenocarcinoma.

Background: The use of free tissue transfer (FTT) is efficacious for chronic, non-healing lower extremity (LE) wounds. The four pillars of managing patient comorbidities, infection control, blood flow status, and biomechanical function are critical in achieving successful limb salvage. The authors present their multidisciplinary institutional experience with a review of 300 FTTs performed for the complex LE limb salvage of chronic LE wounds. Methods: A single-institution, retrospective review of atraumatic LE FTTs performed by a single surgeon from July 2011 to January 2023 was reviewed. Data on patient demographics, comorbidities, preoperative management, intraoperative details, flap outcomes, postoperative complications, and long-term outcomes were collected. Results: A total of 300 patients who underwent LE FTT were included in our retrospective review. Patients were on average 55.9 ± 13.6 years old with a median Charlson Comorbidity Index of 4 (IQR: 3). The majority of patients were male (70.7%). The overall hospital length of stay (LOS) was 27 days (IQR: 16), with a postoperative LOS of 14 days (IQR: 9.5). The most prevalent comorbidities were diabetes (54.7%), followed by peripheral vascular disease (PVD: 35%) and chronic kidney disease (CKD: 15.7%). The average operative LE FTT time was 416 ± 115 min. The majority of flaps were anterolateral thigh (ALT) flaps (52.7%), followed by vastus lateralis (VL) flaps (25.3%). The immediate flap success rate was 96.3%. The postoperative ipsilateral amputation rate was 12.7%. Conclusions: Successful limb salvage is possible in a highly comorbid patient population with a high prevalence of diabetes mellitus, peripheral vascular disease, and end-stage renal disease. In order to optimize patients prior to their LE FTT, extensive laboratory, arterial, and venous preoperative testing and diabetes management are needed preoperatively. Postoperative monitoring and long-term follow-up with a multidisciplinary team are also crucial for long-term limb salvage success.