An auxin-regulable oscillatory circuit drives the root clock in Arabidopsis

CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA)In Arabidopsis, the root clock regulates the spacing of lateral organs along the primary root through oscillating gene expression. The core molecular mechanism that drives the root clock periodicity and how it is modified by exogenous cues such as auxin and gravity remain unknown. We identified the key elements of the oscillator (AUXIN RESPONSE FACTOR 7, its auxin-sensitive inhibitor IAA18/POTENT, and auxin) that form a negative regulatory loop circuit in the oscillation zone. Through multilevel computer modeling fitted to experimental data, we explain how gene expression oscillations coordinate with cell division and growth to create the periodic pattern of organ spacing. Furthermore, gravistimulation experiments based on the model predictions show that external auxin stimuli can lead to entrainment of the root clock. Our work demonstrates the mechanism underlying a robust biological clock and how it can respond to external stimuli.This work was funded by the Ministerio de Economía y Competitividad of Spain (MINECO) and/or the ERDF (BFU2016-80315-P to M.A.M.-R., BIO2017-82209-R to J.C.d.P., and TIN2016-81079-R to A.R.-P.), the Comunidad de Madrid and/or ERDF and ESF (2017-T1/BIO-5654 to K.W. and S2017/BMD-3691 to A.R.-P.), the Howard Hughes Medical Institute and the NIH (R35-GM131725 to P.N.B.), the Fonds Wetenschappelijk Onderzoek (FWO Flanders) (G022516N, G020918N, and G024118N to T.B.), and the “Severo Ochoa Program for Centres of Excellence in R&D” from the Agencia Estatal de Investigacion of Spain [SEV-2016-0672 (2017–2021)] to K.W., P.P.-G., and M.A.M.-R. through CBGP. M.M. was supported by a postdoctoral contract associated to SEV-2016-0672, E.B.-A. by Ayudante de Investigacion contract PEJ-2017-AI/BIO-7360 from the Comunidad de Madrid, A.S.-C. and L.S.-R. by FPI contracts from MINECO (BES-2014-068852 and BES-2017-080155, respectively), J.C. by a Juan de la Cierva contract from MINECO (FJCI-2016-28607), P.P.-G. by a Juan de la Cierva contract from MINECO (FJCI-2015-24905) and Programa Atraccion Talento from Comunidad Madrid (2017-T2/BIO-3453), A.S. by a Torres Quevedo contract from MINECO (PTQ-15-07915), and K.W. by program PGC2018-093387-A-I00 from the Ministerio de Ciencia e Innovacion (MICIU)Peer reviewe

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. Conclusion: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective