DNA-binding by Haemophilus influenzae and Escherichia coli YbaB, members of a widely-distributed bacterial protein family

BACKGROUND: Genes orthologous to the ybaB loci of Escherichia coli and Haemophilus influenzae are widely distributed among eubacteria. Several years ago, the three-dimensional structures of the YbaB orthologs of both E. coli and H. influenzae were determined, revealing a novel tweezer -like structure. However, a function for YbaB had remained elusive, with an early study of the H. influenzae ortholog failing to detect DNA-binding activity. Our group recently determined that the Borrelia burgdorferi YbaB ortholog, EbfC, is a DNA-binding protein. To reconcile those results, we assessed the abilities of both the H. influenzae and E. coli YbaB proteins to bind DNA to which B. burgdorferi EbfC can bind. RESULTS: Both the H. influenzae and the E. coli YbaB proteins bound to tested DNAs. DNA-binding was not well competed with poly-dI-dC, indicating some sequence preferences for those two proteins. Analyses of binding characteristics determined that both YbaB orthologs bind as homodimers. Different DNA sequence preferences were observed between H. influenzae YbaB, E. coli YbaB and B. burgdorferi EbfC, consistent with amino acid differences in the putative DNA-binding domains of these proteins. CONCLUSION: Three distinct members of the YbaB/EbfC bacterial protein family have now been demonstrated to bind DNA. Members of this protein family are encoded by a broad range of bacteria, including many pathogenic species, and results of our studies suggest that all such proteins have DNA-binding activities. The functions of YbaB/EbfC family members in each bacterial species are as-yet unknown, but given the ubiquity of these DNA-binding proteins among Eubacteria, further investigations are warranted

Mycorrhizal feedbacks influence global forest structure and diversity

One mechanism proposed to explain high species diversity in tropical systems is strong negative conspecific density dependence (CDD), which reduces recruitment of juveniles in proximity to conspecific adult plants. Although evidence shows that plant-specific soil pathogens can drive negative CDD, trees also form key mutualisms with mycorrhizal fungi, which may counteract these effects. Across 43 large-scale forest plots worldwide, we tested whether ectomycorrhizal tree species exhibit weaker negative CDD than arbuscular mycorrhizal tree species. We further tested for conmycorrhizal density dependence (CMDD) to test for benefit from shared mutualists. We found that the strength of CDD varies systematically with mycorrhizal type, with ectomycorrhizal tree species exhibiting higher sapling densities with increasing adult densities than arbuscular mycorrhizal tree species. Moreover, we found evidence of positive CMDD for tree species of both mycorrhizal types. Collectively, these findings indicate that mycorrhizal interactions likely play a foundational role in global forest diversity patterns and structure

Carbon carrying capacity in primary forests shows potential for mitigation achieving the European Green Deal 2030 target

13 Pág.Carbon accounting in the land sector requires a reference level from which to calculate past losses of carbon and potential for gains using a stock-based target. Carbon carrying capacity represented by the carbon stock in primary forests is an ecologically-based reference level that allows estimation of the mitigation potential derived from protecting and restoring forests to increase their carbon stocks. Here we measured and collated tree inventory data at primary forest sites including from research studies, literature and forest inventories (7982 sites, 288,262 trees, 27 countries) across boreal, temperate, and subtropical Global Ecological Zones within Europe. We calculated total biomass carbon stock per hectare (above- and below-ground, dead biomass) and found it was 1.6 times larger on average than modelled global maps for primary forests and 2.3 times for all forests. Large trees (diameter greater than 60 cm) accounted for 50% of biomass and are important carbon reservoirs. Carbon stock foregone by harvesting of 12–52% demonstrated the mitigation potential. Estimated carbon gain by protecting, restoring and ongoing growth of existing forests equated to 309 megatons carbon dioxide equivalents per year, additional to, and higher than, the current forest sink, and comparable to the Green Deal 2030 target for carbon dioxide removals.We thank the many people involved with the collection and provision of the site data and recognise the significant resources, people and time required to collect this invaluable data. The research for the synthesis, analysis and writing (H.K., Z.K., S.H., B.M.) was supported by a grant from a charitable organisation which neither seeks nor permits publicity for its efforts. The funder had no involvement in the study design, results or publication of the paper. Site data from Spain was funded by the Spanish Ministry of Science, Innovation and Universities [AGL2016-76769-C2-2-R]. C.P.C. was supported by the Spanish Ministry of Science and Innovation [RYC2018-024939-I]. J.A.M.V. was supported by the Ramón Areces Foundation Grants for Postdoctoral Studies. Contribution of D.A., K.K. and P.S. as well as data collection and processing from Czech natural forests was supported by Czech Science Foundation, project no. 24-11119S. D.M.-B. was funded by projects AGL2015-73190-JIN, PID2019-110273RB-I00 and contract RYC-2017-23389 by the Spanish Ministry of Science and Innovation MCIN/AEI. V.B. and I.D. were supported by the FORCLIMIT project funded in the frame of the ERA-NET FACCE ERA-GAS and with national support from Romanian National Authority for Scientific Research and Innovation, CCCDI \u2013 UEFISCDI [grant number 82/2017]. FACCE ERA-GAS has received funding from the European Union\u2019s Horizon 2020 research and innovation programme [grant agreement 696356. T.Z. was funded by The WWF Bulgaria through the project IKEA \u2116 9E0710.05 and by The National Roadmap for Research Infrastructure (2020-2027), Ministry of Education and Science of Republic of Bulgaria, through agreements No DO1-405/18.12.2020 and DO1-163/28.07.2022 (LTER-BG). L.D. was funded by the project of the National Research, Development and Innovation Office NKFIH K 131837. T.N. received support from the Slovenian Research Agency (Project No. J4-1765). For additional assistance with site data, we thank Dr. Ra\u00FAl Sanchez-Salguero and Dr. Andrea Hevia for evaluating the age in the dendrochronological samples in Spain, and Nesibe K\u00F6se, Mehmet Do\u011Fan, Daniel Bishop, Marco Mina, Timothy Thrippleton, Neil Pederson, Guillermo Gea-Izquierdo and Macarena F\u00E9rriz for their help during fieldwork, and Cengiz Cihan and the Turkish General Directorate of Forestry (OGM) in Bor\u00E7ka (Artvin) for their assistance in the field in Turkey.Peer reviewe

Mycorrhizal feedbacks influence global forest structure and diversity

One mechanism proposed to explain high species diversity in tropical systems is strong negative conspecific density dependence (CDD), which reduces recruitment of juveniles in proximity to conspecific adult plants. Although evidence shows that plant-specific soil pathogens can drive negative CDD, trees also form key mutualisms with mycorrhizal fungi, which may counteract these effects. Across 43 large-scale forest plots worldwide, we tested whether ectomycorrhizal tree species exhibit weaker negative CDD than arbuscular mycorrhizal tree species. We further tested for conmycorrhizal density dependence (CMDD) to test for benefit from shared mutualists. We found that the strength of CDD varies systematically with mycorrhizal type, with ectomycorrhizal tree species exhibiting higher sapling densities with increasing adult densities than arbuscular mycorrhizal tree species. Moreover, we found evidence of positive CMDD for tree species of both mycorrhizal types. Collectively, these findings indicate that mycorrhizal interactions likely play a foundational role in global forest diversity patterns and structure

Approval of Syringe Exchange Programs in California: Results From a Local Approach to HIV Prevention

Objectives. We studied the effect of local approval of syringe exchange programs in California (through Assembly AB136) on program availability and performance

DNA-binding by <it>Haemophilus influenzae </it>and <it>Escherichia coli </it>YbaB, members of a widely-distributed bacterial protein family

Abstract Background Genes orthologous to the ybaB loci of Escherichia coli and Haemophilus influenzae are widely distributed among eubacteria. Several years ago, the three-dimensional structures of the YbaB orthologs of both E. coli and H. influenzae were determined, revealing a novel "tweezer"-like structure. However, a function for YbaB had remained elusive, with an early study of the H. influenzae ortholog failing to detect DNA-binding activity. Our group recently determined that the Borrelia burgdorferi YbaB ortholog, EbfC, is a DNA-binding protein. To reconcile those results, we assessed the abilities of both the H. influenzae and E. coli YbaB proteins to bind DNA to which B. burgdorferi EbfC can bind. Results Both the H. influenzae and the E. coli YbaB proteins bound to tested DNAs. DNA-binding was not well competed with poly-dI-dC, indicating some sequence preferences for those two proteins. Analyses of binding characteristics determined that both YbaB orthologs bind as homodimers. Different DNA sequence preferences were observed between H. influenzae YbaB, E. coli YbaB and B. burgdorferi EbfC, consistent with amino acid differences in the putative DNA-binding domains of these proteins. Conclusion Three distinct members of the YbaB/EbfC bacterial protein family have now been demonstrated to bind DNA. Members of this protein family are encoded by a broad range of bacteria, including many pathogenic species, and results of our studies suggest that all such proteins have DNA-binding activities. The functions of YbaB/EbfC family members in each bacterial species are as-yet unknown, but given the ubiquity of these DNA-binding proteins among Eubacteria, further investigations are warranted.</p

A Matching-adjusted Indirect Comparison of Nivolumab Plus Cabozantinib Versus Pembrolizumab Plus Axitinib in Patients with Advanced Renal Cell Carcinoma

Background: The comparative efficacy and health-related quality of life (HRQoL) outcomes of nivolumab plus cabozantinib versus pembrolizumab plus axitinib as first-line treatments for advanced renal cell carcinoma (aRCC) have not been assessed in head-to-head trials. Objective: To assess the efficacy and HRQoL outcomes of nivolumab plus cabozantinib versus pembrolizumab plus axitinib. Design, setting, and participants: Patient-level data for nivolumab plus cabozantinib from the CheckMate 9ER trial and published data for pembrolizumab plus axitinib from the KEYNOTE-426 trial were used. CheckMate 9ER data were reweighted to match the key baseline characteristics as reported in KEYNOTE-426. Intervention: Nivolumab (240 mg every 2 wk) plus cabozantinib (40 mg once daily) and pembrolizumab (200 mg every 3 wk) plus axitinib (5 mg twice daily, initially). Outcome measurements and statistical analysis: Hazard ratios (HRs) for progression-free survival (PFS), duration of response, overall survival (OS), and deterioration in HRQoL were assessed using weighted Cox proportional-hazard models, with sunitinib as a common anchor. Objective response rates (ORRs) and changes in HRQoL scores from baseline were assessed as difference-in-differences for the two treatments relative to sunitinib. Results and limitations: After balancing patient characteristics between the trials, nivolumab plus cabozantinib was associated with significantly improved PFS (HR [95% confidence interval {CI}] 0.70 [0.53-0.93]; p&nbsp;=&nbsp;0.01) and a significantly decreased risk of confirmed deterioration in HRQoL (Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease-related Symptoms: HR [95% CI] 0.48 [0.34-0.69]) versus pembrolizumab plus axitinib. OS was similar between treatments (HR [95% CI] 0.99 [0.67-1.44]; p&nbsp;=&nbsp;0.94). Nivolumab plus cabozantinib was associated with numerically greater ORRs (difference-in-difference [95% CI] 8.4% [-1.7 to 18.4]; p&nbsp;=&nbsp;0.10) and longer duration of response (HR [95% CI] 0.79 [0.47-1.31]; p&nbsp;=&nbsp;0.36) than pembrolizumab plus axitinib. Comparative studies using data with a longer duration of follow-up are warranted. Conclusions: Nivolumab plus cabozantinib significantly improved PFS and HRQoL compared with pembrolizumab plus axitinib as first-line treatment for aRCC. Patient summary: This study was conducted to indirectly compare the results of two immunotherapy-based combinations-nivolumab plus cabozantinib versus pembrolizumab plus axitinib-for patients who have not received any treatment for advanced renal cell carcinoma. Patients who received nivolumab plus cabozantinib had a significant improvement in the length of time without worsening of their disease and in their perceived physical and mental health compared with pembrolizumab plus axitinib; patients remained alive for a similar length of time from the start of either treatment. This analysis further adds to our current knowledge of the relative benefits of these two treatment regimens and will help with physician and patient treatment decisions

The Toronto Upper Gastrointestinal Cleaning Score: a prospective validation study

Background Assessment of mucosal visualization during esophagogastroduodenoscopy (EGD) can be improved with a standardized scoring system. To address this need, we created the Toronto Upper Gastrointestinal Cleaning Score (TUGCS). Methods We developed the TUGCS using Delphi methodology, whereby an international group of endoscopy experts iteratively rated their agreement with proposed TUGCS items and anchors on a 5-point Likert scale. After each Delphi round, we analyzed responses and refined the TUGCS using an 80% agreement threshold for consensus. We used the intraclass correlation coefficient (ICC) to assess inter-rater and test-retest reliability. We assessed internal consistency with Cronbach's alpha and item-total and inter-item correlations with Pearson's correlation coefficient. We compared TUGCS ratings with an independent endoscopist's global rating of mucosal visualization using Spearman's rho. Results We achieved consensus with 14 invited participants after three Delphi rounds. Inter-rater reliability was high at 0.79 (95%CI 0.64-0.88). Test-retest reliability was excellent at 0.83 (95%CI 0.77-0.87). Cronbach's alpha was 0.81, item-total correlation range was 0.52-0.70, and inter-item correlation range was 0.38-0.74. There was a positive correlation between TUGCS ratings and a global rating of visualization (r=0.41, P=0.002). TUGCS ratings for EGDs with global ratings of excellent were significantly higher than those for EGDs with global ratings of fair (P=0.01). Conclusion The TUGCS had strong evidence of validity in the clinical setting. The international group of assessors, broad variety of EGD indications, and minimal assessor training improves the potential for dissemination