Adaptive remodeling of the bacterial proteome by specific ribosomal modification regulates Pseudomonas infection and niche colonisation

Post-transcriptional control of protein abundance is a highly important, underexplored regulatory process by which organisms respond to their environments. Here we describe an important and previously unidentified regulatory pathway involving the ribosomal modification protein RimK, its regulator proteins RimA and RimB, and the widespread bacterial second messenger cyclic-di-GMP (cdG). Disruption of rimK affects motility and surface attachment in pathogenic and commensal Pseudomonas species, with rimK deletion significantly compromising rhizosphere colonisation by the commensal soil bacterium P. fluorescens, and plant infection by the pathogens P. syringae and P. aeruginosa. RimK functions as an ATP-dependent glutamyl ligase, adding glutamate residues to the C-terminus of ribosomal protein RpsF and inducing specific effects on both ribosome protein complement and function. Deletion of rimK in P. fluorescens leads to markedly reduced levels of multiple ribosomal proteins, and also of the key translational regulator Hfq. In turn, reduced Hfq levels induce specific downstream proteomic changes, with significant increases in multiple ABC transporters, stress response proteins and non-ribosomal peptide synthetases seen for both ΔrimK and Δhfq mutants. The activity of RimK is itself controlled by interactions with RimA, RimB and cdG. We propose that control of RimK activity represents a novel regulatory mechanism that dynamically influences interactions between bacteria and their hosts; translating environmental pressures into dynamic ribosomal changes, and consequently to an adaptive remodeling of the bacterial proteome

Stationary cocycles and Busemann functions for the corner growth model

We study the directed last-passage percolation model on the planar square lattice with nearest-neighbor steps and general i.i.d. weights on the vertices, out- side of the class of exactly solvable models. Stationary cocycles are constructed for this percolation model from queueing fixed points. These cocycles serve as bound- ary conditions for stationary last-passage percolation, solve variational formulas that characterize limit shapes, and yield existence of Busemann functions in directions where the shape has some regularity. In a sequel to this paper the cocycles are used to prove results about semi-infinite geodesics and the competition interface

Dimerisation induced formation of the active site and the identification of three metal sites in EAL-phosphodiesterases

The bacterial second messenger cyclic di-3′,5′-guanosine monophosphate (c-di-GMP) is a key regulator of bacterial motility and virulence. As high levels of c-di-GMP are associated with the biofilm lifestyle, c-di-GMP hydrolysing phosphodiesterases (PDEs) have been identified as key targets to aid development of novel strategies to treat chronic infection by exploiting biofilm dispersal. We have studied the EAL signature motif-containing phosphodiesterase domains from the Pseudomonas aeruginosa proteins PA3825 (PA3825EAL) and PA1727 (MucREAL). Different dimerisation interfaces allow us to identify interface independent principles of enzyme regulation. Unlike previously characterised two-metal binding EAL-phosphodiesterases, PA3825EAL in complex with pGpG provides a model for a third metal site. The third metal is positioned to stabilise the negative charge of the 5′-phosphate, and thus three metals could be required for catalysis in analogy to other nucleases. This newly uncovered variation in metal coordination may provide a further level of bacterial PDE regulation

Geodesics and the competition interface for the corner growth model

We study the directed last-passage percolation model on the planar square lattice with nearest-neighbor steps and general i.i.d. weights on the vertices, out- side of the class of exactly solvable models. Stationary cocycles are constructed for this percolation model from queueing fixed points. These cocycles serve as bound- ary conditions for stationary last-passage percolation, solve variational formulas that characterize limit shapes, and yield existence of Busemann functions in directions where the shape has some regularity. In a sequel to this paper the cocycles are used to prove results about semi-infinite geodesics and the competition interface

A Rac/Cdc42 exchange factor complex promotes formation of lateral filopodia and blood vessel lumen morphogenesis

During angiogenesis, Rho GTPases influence endothelial cell migration and cell-cell adhesion; however it is not known whether they control formation of vessel lumens, which are essential for blood flow. Here, using an organotypic system that recapitulates distinct stages of VEGF-dependent angiogenesis, we show that lumen formation requires early cytoskeletal remodelling and lateral cell-cell contacts, mediated through the RAC1 guanine nucleotide exchange factor (GEF) DOCK4. DOCK4 signalling is necessary for lateral filopodial protrusions and tubule remodelling prior to lumen formation, whereas proximal, tip filopodia persist in the absence of DOCK4. VEGF-dependent Rac activation via DOCK4 is necessary for CDC42 activation to signal filopodia formation and depends on the activation of RHOG through the RHOG GEF, SGEF. VEGF promotes interaction of DOCK4 with the CDC42 GEF DOCK9. These studies identify a novel Rho-family GTPase activation cascade for the formation of endothelial cell filopodial protrusions necessary for tubule remodelling, thereby influencing subsequent stages of lumen morphogenesis

Effectiveness and Safety of Radiofrequency Catheter Ablation Using Three-Dimensional Electroanatomic Mapping Systems in Treating Ventricular Arrhythmias: A Single-Center Prospective Cohort Study in Vietnam

Le Uyen Phuong Tran,1 Ngoc Dung Kieu,1 Cao Dat Tran,1 Tri-Thuc Nguyen,1 Van Sy Hoang,2 Truc Thanh Thai3 1Department of Arrhythmology, Cho Ray Hospital, Ho Chi Minh City, Vietnam; 2Department of Internal Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam; 3Department of Medical Statistics and Informatics, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, VietnamCorrespondence: Truc Thanh Thai, Department of Medical Statistics and Informatics, University of Medicine and Pharmacy at Ho Chi Minh City, 217 Hong Bang Street, Ward 11, District 5, Ho Chi Minh City, 700000, Vietnam, Tel +84 908381266, Email [email protected]: Advanced catheter ablation using three-dimensional electroanatomic mapping (EAM) has shown favorable outcomes in high-income countries, but real-world evidence from low- and middle-income settings is scarce. This study aimed to assess the clinical characteristics, procedural features, and outcomes of radiofrequency ablation using EAM in patients with ventricular tachycardia (VT) or premature ventricular contractions (PVCs) at a tertiary cardiac center in Vietnam.Methods: We analyzed 233 patients who underwent VT and PVC ablation at Cho Ray Hospital from March 2021 to December 2023. Patients were categorized into two groups based on left ventricular ejection fraction (LVEF) with the cut-off value of 50%: reduced (LVEF < 50%, n = 39) and preserved (LVEF ≥ 50%, n = 194). Data on demographics, arrhythmia burden, ablation protocol, and follow-up outcomes were collected and compared.Results: Patients with reduced LVEF more frequently presented with ventricular tachycardia (23.1% vs 6.7%, p < 0.001), ischemic heart disease (23.1% vs 7.7%, p = 0.008), and were more likely to require irrigated catheters (46.2% vs 20.1%, p = 0.001). The PVC burden prior to ablation was significantly different between groups (36.3% ± 17.2 vs 27.8% ± 12.2, p = 0.014) and patients with reduced LVEF exhibited remarkable recovery after ablation, with LVEF improving from 33.7 ± 8.1 to 55.2 ± 9.1 (p < 0.001). The acute ablation success rate was 100% in both groups. The procedure demonstrated high levels of safety, with a non-severe complication rate of 4.7% (n = 11) and low radiation exposure (median 16 mGy [inter-quartile range: 11– 26]).Conclusion: Catheter ablation is highly effective and safe in treating ventricular arrhythmias across different LVEF, especially in ventricular arrhythmia-induced cardiomyopathy group, leading to rapid recovery of left ventricular function and reduction in arrhythmia burden. These findings provide important real-world evidence from a resource limited setting, providing multiple use of catheters and skin patches.Keywords: safety, effectiveness, ventricular arrhythmias induced cardiomyopathy, radiofrequency catheter ablation, heart failur

Efficient low-loaded ternary Pd-In2O3-Al2O3 catalysts for methanol production

Pd-In2O3 catalysts are among the most promising alternatives to Cu-ZnO-Al2O3 for synthesis of CH3OH from CO2. However, the intrinsic activity and stability of In2O3 per unit mass should be increased to reduce the content of this scarcely available element and to enhance the catalyst lifetime. Herein, we propose and demonstrate a strategy for obtaining highly dispersed Pd and In2O3 nanoparticles onto an Al2O3 matrix by a one-step coprecipitation followed by calcination and activation. The activity of this catalyst is comparable with that of a Pd-In2O3 catalyst (0.52 vs 0.55 gMeOH h−1 gcat-1 at 300 °C, 30 bar, 40,800 mL h−1 gcat-1) but the In2O3 loading decreases from 98 to 12 wt% while improving the long-term stability by threefold at 30 bar. In the new Pd-In2O3-Al2O3 system, the intrinsic activity of In2O3 is highly increased both in terms of STY normalized to In specific surface area and In2O3 mass (4.32 vs 0.56 g gMeOH h−1 gIn2O3-1 of a Pd- In2O3 catalyst operating at 300 °C, 30 bar, 40,800 mL h−1 gcat-1).The combination of ex situ and in situ catalyst characterizations during reduction provides insights into the interaction between Pd and In and with the support. The enhanced activity is likely related to the close proximity of Pd and In2O3, wherein the H2 splitting activity of Pd promotes, in combination with CO2 activation over highly dispersed In2O3 particles, facile formation of CH3OH

Air pollution and the incidence of ischaemic and haemorrhagic stroke in the South London stroke register: A case-cross-over analysis

Background Few European studies investigating associations between short-term exposure to air pollution and incident stroke have considered stroke subtypes. Using information from the South London Stroke Register for 2005-2012, we investigated associations between daily concentrations of gaseous and particulate air pollutants and incident stroke subtypes in an ethnically diverse area of London, UK. Methods Modelled daily pollutant concentrations based on a combination of measurements and dispersion modelling were linked at postcode level to incident stroke events stratified by haemorrhagic and ischaemic subtypes. The data were analysed using a time-stratified case-cross-over approach. Conditional logistic regression models included natural cubic splines for daily mean temperature and daily mean relative humidity, a binary term for public holidays and a sine-cosine annual cycle. Of primary interest were same day mean concentrations of particulate matter < 2.5 and < 10 mm in diameter (PM 2.5 , PM 10 ), ozone (O 3 ), nitrogen dioxide (NO 2 ) and NO 2+ nitrogen oxide (NO X ). Results Our analysis was based on 1758 incident strokes (1311 were ischaemic and 256 were haemorrhagic). We found no evidence of an association between all stroke or ischaemic stroke and same day exposure to (PM 2.5 , PM 10 ), (O 3 ), (NO 2 ) or (NO X ). For haemorrhagic stroke, we found a negative association with PM10 suggestive of a 14.6% (95% CI 0.7% to 26.5%) fall in risk per 10 mg/m3 increase in pollutant. Conclusions Using data from the South London Stroke Register, we found no evidence of a positive association between outdoor air pollution and incident stroke or its subtypes. These results, though in contrast to recent meta-analyses, are not inconsistent with the mixed findings of other UK studies