To make or take: bacterial lipid homeostasis during Infection

Bacterial fatty acids are critical components of the cellular membrane. A shift in environmental conditions or in the bacterium’s lifestyle may result in the requirement for a distinct pool of fatty acids with unique biophysical properties. This can be achieved by the modification of existing fatty acids or via de novo synthesis. Furthermore, bacteria have evolved efficient means to acquire these energy-rich molecules from their environment. However, the balance between de novo fatty acid synthesis and exogenous acquisition during pathogenesis is poorly understood. Here, we studied the mouse fatty acid landscape prior to and after infection with Acinetobacter baumannii, a Gram-negative, opportunistic human pathogen. The lipid fluxes observed following infection revealed fatty acid- and niche-specific changes. Lipidomic profiling of A. baumannii isolated from the pleural cavity of mice identified novel A. baumannii membrane phospholipid species and an overall increased abundance of unsaturated fatty acid species. Importantly, we found that A. baumannii relies largely upon fatty acid acquisition in all but one of the studied niches, the blood, where the pathogen biosynthesizes its own fatty acids. This work is the first to reveal the significance of balancing the making and taking of fatty acids in a Gram-negative bacterium during infection, which provides new insights into the validity of targeting fatty acid synthesis as a treatment strategy.Felise G. Adams, Claudia Trappetti, Jack K. Waters, Maoge Zang, Erin B. Brazel, James C. Paton, Marten F. Snel, Bart A. Eijkelkam

Supersymmetric Regularization, Two-Loop QCD Amplitudes and Coupling Shifts

We present a definition of the four-dimensional helicity (FDH) regularization scheme valid for two or more loops. This scheme was previously defined and utilized at one loop. It amounts to a variation on the standard 't Hooft-Veltman scheme and is designed to be compatible with the use of helicity states for "observed" particles. It is similar to dimensional reduction in that it maintains an equal number of bosonic and fermionic states, as required for preserving supersymmetry. Supersymmetry Ward identities relate different helicity amplitudes in supersymmetric theories. As a check that the FDH scheme preserves supersymmetry, at least through two loops, we explicitly verify a number of these identities for gluon-gluon scattering (gg to gg) in supersymmetric QCD. These results also cross-check recent non-trivial two-loop calculations in ordinary QCD. Finally, we compute the two-loop shift between the FDH coupling and the standard MS-bar coupling, alpha_s. The FDH shift is identical to the one for dimensional reduction. The two-loop coupling shifts are then used to obtain the three-loop QCD beta function in the FDH and dimensional reduction schemes.Comment: 44 pages, minor corrections and clarifications include

Detrimental immediate and medium-term clinical effects of right ventricular pacing in patients with myocardial fibrosis.

Background: Long-term right ventricular (RV) pacing leads to heart failure or a decline in left ventricular (LV) function in up to a fifth of patients. We aimed to establish whether patients with focal fibrosis detected on late gadolinium enhancement cardiovascular magnetic resonance (CMR) have deterioration in LV function after RV pacing. Methods: We recruited 84 patients with LV ejection fraction ≥40% into 2 observational CMR studies. Patients (n=34) with a dual-chamber device and preserved atrioventricular conduction underwent CMR in 2 asynchronous pacing modes (atrial asynchronous and dual-chamber asynchronous) to compare intrinsic atrioventricular conduction with forced RV pacing. Patients (n=50) with high-grade atrioventricular block underwent CMR before and 6 months after pacemaker implantation to investigate the medium-term effects of RV pacing. Results: The key findings were (1) initiation of RV pacing in patients with fibrosis, compared with those without, was associated with greater immediate changes in both LV end-systolic volume index (5.3±3.5 versus 2.1±2.4 mL/m2; P1.1 g of fibrosis with 90% sensitivity and 70% specificity. Conclusions: Fibrosis detected on CMR is associated with immediate- and medium-term deterioration in LV function following RV pacing and could be used to identify those at risk of heart failure before pacemaker implantation

4D Flow Cardiac MR in Primary Mitral Regurgitation

Background Four-dimensional-flow cardiac MR (4DF-MR) offers advantages in primary mitral regurgitation. The relationship between 4DF-MR-derived mitral regurgitant volume (MR-Rvol) and the post-operative left ventricular (LV) reverse remodeling has not yet been established. Purpose To ascertain if the 4DF-MR-derived MR-Rvol correlates with the LV reverse remodeling in primary mitral regurgitation. Study Type Prospective, single-center, two arm, interventional vs. nonintervention observational study. Population Forty-four patients (male N = 30; median age 68 [59–75]) with at least moderate primary mitral regurgitation; either awaiting mitral valve surgery (repair [MVr], replacement [MVR]) or undergoing “watchful waiting” (WW). Field Strength/Sequence 5 T/Balanced steady-state free precession (bSSFP) sequence/Phase contrast imaging/Multishot echo-planar imaging pulse sequence (five shots). Assessment Patients underwent transthoracic echocardiography (TTE), phase-contrast MR (PMRI), 4DF-MR and 6-minute walk test (6MWT) at baseline, and a follow-up PMRI and 6MWT at 6 months. MR-Rvol was quantified by PMRI, 4DF-MR, and TTE by one observer. The pre-operative MR-Rvol was correlated with the post-operative decrease in the LV end-diastolic volume index (LVEDVi). Statistical Tests Included Student t-test/Mann–Whitney test/Fisher's exact test, Bland–Altman plots, linear regression analysis and receiver operating characteristic curves. Statistical significance was defined as P < 0.05. Results While Bland–Altman plots demonstrated similar bias between all the modalities, the limits of agreement were narrower between 4DF-MR and PMRI (bias 15; limits of agreement −36 mL to 65 mL), than between 4DF-MR and TTE (bias −8; limits of agreement −106 mL to 90 mL) and PMRI and TTE (bias −23; limits of agreement −105 mL to 59 mL). Linear regression analysis demonstrated a significant association between the MR-Rvol and the post-operative decrease in the LVEDVi, when the MR-Rvol was quantified by PMRI and 4DF-MR, but not by TTE (P = 0.73). 4DF-MR demonstrated the best diagnostic performance for reduction in the post-operative LVEDVi with the largest area under the curve (4DF-MR 0.83; vs. PMRI 0.78; and TTE 0.51; P = 0.89). Data Conclusion This study demonstrates the potential clinical utility of 4DF-MR in the assessment of primary mitral regurgitation

State of the world’s plants and fungi 2020

Kew’s State of the World’s Plants and Fungi project provides assessments of our current knowledge of the diversity of plants and fungi on Earth, the global threats that they face, and the policies to safeguard them. Produced in conjunction with an international scientific symposium, Kew’s State of the World’s Plants and Fungi sets an important international standard from which we can annually track trends in the global status of plant and fungal diversity

Global Retinoblastoma Presentation and Analysis by National Income Level

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4) were female. Most patients (n = 3685 84.7%) were from low-and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 62.8%), followed by strabismus (n = 429 10.2%) and proptosis (n = 309 7.4%). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 95% CI, 12.94-24.80, and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 95% CI, 4.30-7.68). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs. © 2020 American Medical Association. All rights reserved