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The concept of “solution spaces” is used to explore the potential future of forestry under climate change for different types of forestry management structures. We base the analysis in New Zealand, where forestry plays an increasingly critical role in the nation’s climate policy, but the concept could be applied to any region. Understanding solution spaces and the ways in which they can be influenced at different levels of ownership is a critical step towards effective climate change adaptation. Building on the base of existing climate projections, scenarios, and economic and social science literature, we form an assessment of the capacity of each forest owner typology to influence their solution spaces into the future. Different management structures have strengths in different areas – while industrial forest managers may be able to utilise emerging technologies better than their smaller scale counterparts for example, they may be less agile and flexible. The sector as a whole may benefit from working collectively to draw on the respective strengths of each typology. Critically, planning now to expand the space into the future will be essential.

G-proteins are molecular on–off switches that are involved in transmitting a variety of extracellular signals to their intracellular targets. In animal and yeast systems, the switch property is encoded through nucleotides: a GDP-bound state is the “off-state” and the GTP-bound state is the “on-state”. The G-protein cycle consists of the switch turning on through nucleotide exchange facilitated by a G-protein coupled receptor and the switch turning off through hydrolysis of GTP back to GDP, facilitated by a protein designated REGULATOR OF G SIGNALING 1 (RGS). In plants, G-protein signaling dramatically differs from that in animals and yeast. Despite stringent conservation of the nucleotide binding and catalytic structures over the 1.6 billion years that separate the evolution of plants and animals, genetic and biochemical data indicate that nucleotide exchange is less critical for this switch to operate in plants. Also, the loss of the single RGS protein in Arabidopsis (Arabidopsis thaliana) confers unexpectedly weaker phenotypes consistent with a diminished role for the G cycle, at least under static conditions. However, under dynamic conditions, genetic ablation of RGS in Arabidopsis results in a strong phenotype. We explore explanations to this conundrum by formulating a mathematical model that takes into account the accruing evidence for the indispensable role of phosphorylation in G-protein signaling in plants and that the G-protein cycle is needed to process dynamic signal inputs. We speculate that the plant G-protein cycle and its attendant components evolved to process dynamic signals through signaling modulation rather than through on–off, switch-like regulation of signaling. This so-called change detection may impart greater fitness for plants due to their sessility in a dynamic light, temperature, and pest environment.

Samuel Miklos Stern (SMS) was the pioneer of the modern study of both Arabic and Hebrew muwashshaḥāt (a genre of stanzaic lyric poetry). This paper gives an overview of Stern’s ground-breaking cont...

A hydrogeological conceptual model of the source, circulation pathways and temporal variation of a low-enthalpy thermal spring in a fractured limestone setting is derived from a multidisciplinary approach. St. Gorman's Well is a thermal spring in east-central Ireland with a complex and variable temperature profile (maximum of 21.8 °C). Geophysical data from a three-dimensional(3D)audio-magnetotelluric(AMT) survey are combined with time-lapse hydrogeological data and information from a previously published hydrochemical analysis to investigate the operation of this intriguing hydrothermal system. Hydrochemical analysis and time-lapse measurements suggest that the thermal waters flow within the fractured limestones of the Carboniferous Dublin Basin at all times but display variability in discharge and temperature. The 3D electrical resistivity model of the subsurface revealed two prominent structures: (1) a NW-aligned faulted contact between two limestone lithologies; and (2) a dissolutionally enhanced, N-aligned, fault of probable Cenozoic age. The intersection of these two structures, which has allowed for karstification of the limestone bedrock, has created conduits facilitating the operation of relatively deep hydrothermal circulation (likely estimated depths between 240 and 1,000 m) within the limestone succession of the Dublin Basin. The results of this study support a hypothesis that the maximum temperature and simultaneous increased discharge observed at St. Gorman's Well each winter is the result of rapid infiltration, heating and recirculation of meteoric waters within a structurally controlled hydrothermal circulation system.The online version contains supplementary material available at 10.1007/s10040-021-02393-1.Un modèle conceptuel hydrogéologique de la source, des voies de circulation et de la variation temporelle d’une source thermale à faible enthalpie dans un contexte de calcaire fracturé est dérivé d’une approche multidisciplinaire. St. Gorman’s Well est une source thermale du centre-est de l’Irlande avec un profil de température complexe et variable (maximum de 21.8 °C). Les données géophysiques d’un levé audio-magnétotellurique (AMT) en trois dimensions (3D) sont combinées avec des données hydrogéologiques à intervalles de temps et des informations provenant d’une analyse hydrochimique publiée précédemment pour étudier le fonctionnement de cet intrigant système hydrothermal. L’analyse hydrochimique et les mesures à différentes périodes suggèrent que les eaux thermales s’écoulent à tout moment dans les calcaires fracturés du bassin carbonifère de Dublin, mais présentent une variabilité de débit et de température. Le modèle de résistivité électrique 3D du sous-sol a révélé deux structures importantes: (1) un contact faillé orienté NW entre deux lithologies calcaires; et (2) une faille alignée au Nord, améliorée par dissolution, d’âge cénozoïque probable. L’intersection de ces deux structures, qui a permis la karstification du socle calcaire, a créé des conduits facilitant le fonctionnement d’une circulation hydrothermale relativement profonde (profondeurs estimées vraisemblablement entre 240 et 1,000 m) au sein de la succession calcaire du bassin de Dublin. Les résultats de cette étude appuient l’hypothèse selon laquelle la température maximale et l’augmentation simultanée du débit observés à St. Gorman’s Well chaque hiver sont le résultat d’une infiltration, d’un réchauffement et d’une recirculation rapides des eaux météoriques dans un système de circulation hydrothermale structurellement contrôlé.Se deriva un modelo conceptual hidrogeológico de la fuente, las vías de circulación y la variación temporal de un manantial termal de baja entalpía en un entorno de caliza fracturada a partir de un enfoque multidisciplinar. Gorman’s Well es un manantial termal en el centro-este de Irlanda con un perfil de temperatura complejo y variable (máximo de 21.8 °C). Los datos geofísicos de un estudio audio-magnetotelúrico (AMT) tridimensional (3D) se combinan con los datos hidrogeológicos de un lapso de tiempo y la información de un análisis hidroquímico previamente publicado para investigar el funcionamiento de este intrigante sistema hidrotermal. El análisis hidroquímico y las mediciones a intervalos de tiempo sugieren que las aguas termales fluyen dentro de las calizas fracturadas de la cuenca carbonífera de Dublín en todo momento, pero muestran variabilidad en la descarga y la temperatura. El modelo de resistividad eléctrica tridimensional del subsuelo reveló dos estructuras prominentes: (1) un contacto de falla alineado al NW entre dos litologías calcáreas; y (2) una falla de disolución incrementada, alineada al N, de probable edad cenozoica. La intersección de estas dos estructuras, que ha permitido la karstificación del lecho rocoso calcáreo, ha creado conductos que facilitan el funcionamiento de una circulación hidrotermal relativamente profunda (probablemente a profundidades estimadas entre 240 y 1,000 m) dentro de la sucesión calcárea de la cuenca de Dublín. Los resultados de este estudio apoyan la hipótesis de que la temperatura máxima y el aumento simultáneo de la descarga observados en St. Gorman’s Well cada invierno son el resultado de una rápida infiltración, calentamiento y recirculación de aguas meteóricas dentro de un sistema de circulación hidrotermal estructuralmente controlado.通过多学科方法, 建立了裂缝型石灰岩环境中低焓温泉的来源、循环路径和时间变化的水文地质概念模型。圣戈尔曼井是爱尔兰中东部的温泉, 温度分布复杂多变 (最高21.8 °C)。将三维 (3D) 音频-大地电磁 (AMT) 调查的地球物理数据与延时水文地质数据和先前发布的水化学分析信息相结合, 调查了有趣的热液系统运行情况。水化学分析和延时测量表明, 热水一直在石炭系都柏林盆地的裂缝型石灰岩内流动, 但流量和温度有变异性。地下的 3D 电阻率模型揭示了两个突出的结构:(1) 两个石灰岩岩性之间的 NW 向断层接触; 和 (2) 可能新生代的溶蚀增强的和N向的断层。两个结构的交叉点使石灰岩基岩发生岩溶作用, 形成了通道, 促进了都柏林盆地石灰岩序列内相对较深的热液循环 (估计深度可能在 240 至 1,000 m 之间)作用。通过这项研究发现每年冬天在圣戈尔曼井观察到的最高温度和同时增加的排泄量是结构控制的热液循环系统中大气水快速入渗、加热和再循环的结果。.Um modelo hidrogeológico conceitual da fonte, vias de circulação e variação temporal de uma fonte termal de baixa entalpia em um ambiente de calcário fraturado é derivado de uma abordagem multidisciplinar. O poço de St. Gorman é uma fonte termal no centro-leste da Irlanda com um perfil de temperatura complexo e variável (máximo de 21.8°C). Os dados geofísicos de uma pesquisa áudio-magnetotelúrica (AMT) tridimensional (3D) são combinados com dados hidrogeológicos em intervalos de tempo e informações de uma análise hidroquimica publicada anteriormente, para investigar a operação deste intrigante sistema hidrotérmico. A análise hidroquimica e as medições em intervalos de tempo sugerem que as águas termais fluem de dentro dos calcários fraturados da Bacia Carbonifera de Dublin o tempo todo, mas exibem variabilidade na descarga e na temperatura. O modelo de resistividade elétrica 3D da subsuperfície revelou duas estruturas proeminentes: (1) um contato defeituoso alinhado a NO entre duas litologias de calcário; e (2) uma falha dissolucionalmente aumentada, alinhada a N, de provável idade Cenozóica. A intersecção dessas duas estruturas, que permitiu a carstificação da rocha calcária, criou condutos que facilitam a operação de circulação hidrotérmica relativamente profunda (profundidade estimada entre 240 e 1,000 m) dentro da sucessão de calcário da Bacia Dublin. Os resultados desse estudo suportam a hipótese de que a temperatura máxima e o aumento simultâneo da descarga observada no poço de St. Gorman a cada inverno é o resultado da rápida infiltração, aquecimento e recirculação de águas meteóricas dentro de um sistema de circulação hidrotérmica estruturalmente controlado.

Although plastid genome (plastome) structure is highly conserved across most seed plants, investigations during the past two decades revealed several disparately related lineages that experienced substantial rearrangements. Most plastomes contain a large, inverted repeat and two single-copy regions and few dispersed repeats, however the plastomes of some taxa harbor long repeat sequences (>300 bp). These long repeats make it difficult to assemble complete plastomes using short-read data leading to misassemblies and consensus sequences that have spurious rearrangements. Single-molecule, long-read sequencing has the potential to overcome these challenges, yet there is no consensus on the most effective method for accurately assembling plastomes using long-read data. We generated a pipeline,plastidGenomeAssemblyUsingLong-read data (ptGAUL), to address the problem of plastome assembly using long-read data from Oxford Nanopore Technologies (ONT) or Pacific Biosciences platforms. We demonstrated the efficacy of the ptGAUL pipeline using 16 published long-read datasets. We showed that ptGAUL produces accurate and unbiased assemblies. Additionally, we employed ptGAUL to assemble four newJuncus(Juncaceae) plastomes using ONT long reads. Our results revealed many long repeats and rearrangements inJuncusplastomes compared with basal lineages of Poales.

Effective and widely available therapies are still needed for outpatients with COVID-19. We aimed to evaluate the efficacy and safety of lopinavir/ritonavir for early treatment of non-hospitalized individuals diagnosed with COVID-19.This randomized, placebo-controlled, double-blind, multi-site decentralized clinical trial enrolled non-hospitalized adults with confirmed SARS-CoV-2 infection and six or fewer days of acute respiratory infection symptoms who were randomized to either twice daily oral lopinavir/ritonavir (400 mg/100 mg) or placebo for 14 days. Daily surveys on study days 1 through 16 and again on study day 28 evaluated symptoms, daily activities, and hospitalization status. The primary outcome was longitudinal change in an ordinal scale based on combination of symptoms, activity, and hospitalization status through Day 15 and was analyzed by use of a Bayesian longitudinal proportional odds logistic regression model for estimating the probability of a superior recovery for lopinavir/ritonavir over placebo (odds ratio [OR]1).Between June 2020 and December 2021, 448 participants were randomized to receive either lopinavir/ritonavir (n=216) or placebo (n=221). The mean symptom duration prior to randomization was 4.3 days [SD 1.3]. There were no differences between treatment groups through the first 15 days for the ordinal primary outcome (OR 0.96; 95% CrI: 0.66 to 1.41). There were 3.2% (n=7) of lopinavir/ritonavir and 2.7% (n=6) of placebo participants hospitalized by day 28. Serious adverse events did not differ between groups.Lopinavir/ritonavir did not significantly improve symptom resolution or reduce hospitalization in non-hospitalized participants with COVID-19.ClinicalTrials.gov Identifier: NCT04372628.

This article reviews the scientific literature dealing with the distribution of ethanol and water between whole blood (WB), plasma, serum, and erythrocytes (red-blood cells). Knowledge of the ethanol distribution ratio is important when analytical results derived from hospital clinical laboratories are interpreted in a forensic context, such as during the prosecution of traffic offenders. Statutory blood-alcohol concentration (BAC) limits for driving are defined as the concentration of ethanol in WB and not in plasma, serum or red-blood cells. These bio-fluids differ in their water content and thereby the concentrations of ethanol. Plasma and serum contain ~90%-92% w/w water, WB ~78%-80% w/w and erythrocytes ~64%-66% w/w. The mean plasma/WB and serum/WB distribution ratios of ethanol are therefore expected to be ~1.15:1 (91/79 = 1.15), which is in good agreement with values determined empirically. However, in individual cases, the actual distribution ratio will depend on the person's age, gender, and biochemical and hematological properties of the blood specimen, such as its hematocrit. For legal purposes, we recommend that the concentration of ethanol in plasma or serum determined at hospital laboratories is divided by a factor of 1.2, which would provide a conservative estimate of the co-existing BAC and the chance of overestimating the true value is only 1 in 2000 (0.05%).

Acute poisoning involving toxic alcohols other than ethanol is not uncommon. Poisonings from drinking isopropanol are rarely life threatening, whereas methanol and ethylene glycol without prompt treatment cause severe metabolic acidosis, organ damage, and death, mainly due to toxic metabolites. Rapid identification of the type of alcohol responsible for the poisoning requires access to 24/7 toxicological service. The analysis of alcohols is usually done with gas chromatographic (GC) methods, which are not always available at smaller or medium-sized hospitals. As a complement to GC methods, reliable enzymatic oxidation procedures are now available for the analysis of ethanol, methanol, and ethylene glycol. The present study showed good agreement (r2 = 0.996) between the results of methanol analysis with a new enzymatic method (Catachem Inc.) and with GC over the clinically relevant concentration range (1-50 mmol/l). Moreover, high concentrations of ethanol (up to 80 mmol/l), ethylene glycol (to 40 mmol/l), isopropanol (to 100 mmol/l) or acetone (to 20 mmol/l) did not interfere with the analytical results for methanol. Toxicological analysis of the two most dangerous alcohols (methanol and ethylene glycol) can now be done with rapid and specific enzymatic methods, which makes it possible to diagnose and treat poisoned patients at smaller regional hospitals.

Aims The aim of this study was to determine the differences and potential mechanistic rationale for observed adverse drug reactions (ADRs) between four approved PARP inhibitors (PARPi). Methods The Medicines and Healthcare products Regulatory Authority (MHRA) Yellow Card drug analysis profiles and NHS secondary care medicines database enabled the identification of suspected ADRs associated with the PARPi in the UK from launch to 2020. The polypharmacology of the PARPi were data-mined from several public data sources. Results The overall ADRs per 100 000 Rx identified across the four PARPi are statistically significant (χ2 test, P rucaparib > olaparib tracked with the Vd trend. Hypertension is only associated with niraparib and could be explained by the therapeutically achievable inhibition of DYRK1A and/or transporters. Arrhythmia cases are potentially linked to the structural features of hERG ion-channel inhibition found in rucaparib and niraparib. Enhanced psychiatric/nervous disorders associated with niraparib can be interpreted from the diverse neurotransporter off-targets reported. Conclusions Despite their similar mode of action, the differential polypharmacology of PARP inhibitors influences their ADR profile.

Sepsis‐induced metabolic dysfunction contributes to organ failure and death. L‐carnitine has shown promise for septic shock, but a recent phase II study of patients with vasopressor‐dependent septic shock demonstrated a non‐significant reduction in mortality. We undertook a pharmacometabolomics study of these patients (n = 250) to identify metabolic profiles predictive of a 90‐day mortality benefit from L‐carnitine. The independent predictive value of each pretreatment metabolite concentration, adjusted for L‐carnitine dose, on 90‐day mortality was determined by logistic regression. A grid‐search analysis maximizing the Z‐statistic from a binomial proportion test identified specific metabolite threshold levels that discriminated L‐carnitine responsive patients. Threshold concentrations were further assessed by hazard ratio and Kaplan‐Meier estimate. Accounting for L‐carnitine treatment and dose, 11 1H‐NMR metabolites and 12 acylcarnitines were independent predictors of 90‐day mortality. Based on the grid‐search analysis numerous acylcarnitines and valine were identified as candidate metabolites of drug response. Acetylcarnitine emerged as highly viable for the prediction of an L‐carnitine mortality benefit due to its abundance and biological relevance. Using its most statistically significant threshold concentration, patients with pretreatment acetylcarnitine greater than or equal to 35 µM were less likely to die at 90 days if treated with L‐carnitine (18 g) versus placebo (p = 0.01 by log rank test). Metabolomics also identified independent predictors of 90‐day sepsis mortality. Our proof‐of‐concept approach shows how pharmacometabolomics could be useful for tackling the heterogeneity of sepsis and informing clinical trial design. In addition, metabolomics can help understand mechanisms of sepsis heterogeneity and variable drug response, because sepsis induces alterations in numerous metabolite concentrations.

Background and aim Wherever sunlight reaches litter, there is potential for photodegradation to contribute to decomposition. Although recent studies have weighed the contribution of short wavelength visible and ultraviolet (UV) radiation as drivers of photodegradation, the relative importance of each spectral region across biomes and plant communities remains uncertain. Methods We performed a systematic meta-analysis of studies that assessed photodegradation through spectrally selective attenuation of solar radiation, by synthesizing 30 published studies using field incubations of leaf litter from 110 plant species under ambient sunlight. Results Globally, the full spectrum of sunlight significantly increased litter mass loss by 15.3% ± 1% across all studies compared to darkness. Blue light alone was responsible for most of this increase in mass loss (13.8% ± 1%), whereas neither UV radiation nor its individual constituents UV-B and UV-A radiation had significant effects at the global scale, being only important in specific environments. These waveband-dependent effects were modulated by climate and ecosystem type. Among initial litter traits, carbon content, lignin content, lignin to nitrogen ratio and SLA positively correlated with the rate of photodegradation. Global coverage of biomes and spectral regions was uneven across the meta-analysis potentially biasing the results, but also indicating where research in lacking. Conclusions Across studies attenuating spectral regions of sunlight, our meta-analysis confirms that photodegradation is a significant driver of decomposition, but this effect is highly dependent on the spectral region considered. Blue light was the predominant driver of photodegradation across biomes rather than UV radiation.

Herein, we elucidate the biophysical aspects of the interaction of an important protein, Interleukin-6 (IL6), which is involved in cytokine storm syndrome, with a natural product with anti-inflammatory activity, piperine. Despite the role of piperine in the inhibition of the transcriptional protein NF-κB pathway responsible for activation of IL6 gene expression, there are no studies to the best of our knowledge regarding the characterisation of the molecular interaction of the IL6-piperine complex. In this context, the characterisation was performed with spectroscopic experiments aided by molecular modelling. Fluorescence spectroscopy alongside van’t Hoff analyses showed that the complexation event is a spontaneous process driven by non-specific interactions. Circular dichroism aided by molecular dynamics revealed that piperine caused local α-helix reduction. Molecular docking and molecular dynamics disclosed the microenvironment of interaction as non-polar amino acid residues. Although piperine has three available hydrogen bond acceptors, only one hydrogen-bond was formed during our simulation experiments, reinforcing the major role of non-specific interactions that we observed experimentally. Root mean square deviation (RMSD) and hydrodynamic radii revealed that the IL6-piperine complex was stable during 800 ns of simulation. Taken together, these results can support ongoing IL6 drug discovery efforts.

This special section of The Leading Edge focuses on the issue of critical minerals from the perspective of recent progress in mining exploration and anticipated future needs as the global energy economy transitions to higher use of, and reliance on, renewables. The definition of a “critical mineral” is itself context dependent. For example, minerals such as lithium, nickel, cobalt, manganese, and graphite each are essential to the development of modern, high-efficiency lithium-ion batteries, and any disruptions to these minerals — whether through supply chain issues or raw, geologic access — ultimately impacts the future of this now-pervasive, and increasingly necessary, energy storage technology. Similarly, rare earth elements (REEs) have long been central to the manufacture of permanent magnets, which themselves are key components of wind turbines and electric vehicles, the latter of which account for 14% of global passenger car sales in 2022, up from 9% in the previous year. In the United States alone, the market forecast for electric vehicles is expected to grow to roughly US$137 billion in 2028, up from $24 billion in 2020. Lastly, the more “common” but still “critical” minerals copper and aluminum are the backbone of the rapidly expanding global energy distribution systems upon which our modern society is built.

The extra-large guanosine-5′-triphosphate (GTP)-binding protein 2, XLG2, is an unconventional Gα subunit of the Arabidopsis (Arabidopsis thaliana) heterotrimeric GTP-binding protein complex with a major role in plant defense. In vitro biochemical analyses and molecular dynamic simulations show that affinity of XLG2 for GTP is two orders of magnitude lower than that of the conventional Gα, AtGPA1. Here we tested the physiological relevance of GTP binding by XLG2. We generated an XLG2(T476N) variant with abolished GTP binding, as confirmed by in vitro GTPγS binding assay. Yeast three-hybrid, bimolecular fluorescence complementation, and split firefly-luciferase complementation assays revealed that the nucleotide-depleted XLG2(T476N) retained wild-type XLG2-like interactions with the Gβγ dimer and defense-related receptor-like kinases. Both wild-type and nucleotide-depleted XLG2(T476N) restored the defense responses against Fusarium oxysporum and Pseudomonas syringae compromised in the xlg2 xlg3 double mutant. Additionally, XLG2(T476N) was fully functional restoring stomatal density, root growth, and sensitivity to NaCl, but failed to complement impaired germination and vernalization-induced flowering. We conclude that XLG2 is able to function in a GTP-independent manner and discuss its possible mechanisms of action.

A publically available database of the most highly cited scientists in all disciplines was used to identify people that belonged to the subject category “forensic science and legal medicine.” This bibliometric information was derived from Elsevier’s SCOPUS database containing eight million scientists with at least five articles as author or co-author. The top 100,000 most highly cited scientists were identified and ranked according to six citation metrics; total number of citations, H-index, H-index adjusted for co-authorship, citations to single-authored papers, citations to single or first author papers and, citations to single, first, or last-authored papers. The eight million entries in the SCOPUS database were sub-divided into 22 main subject categories and 176 sub-categories, one of which was legal and forensic medicine. The citation databases were provided as supplementary material in two articles published in PLoS Biology in 2019 and 2020. Among the top 100,000 most highly cited scientists, there were only 30 allocated to the legal and forensic medicine category, according to the 2019 PLoS Biology article. The updated database from 2020 also included the names of people within the top-cited 2% of their scientific discipline. This increased the number of forensic practitioners to 215 from a total of 10,158 individuals in this subject category. This article takes a closer look at these highly cited forensic scientists, the countries where they work, the particular research field in which they publish, and their composite citation scores with and without self-citations. The top ten most cited individuals in both databases (2019 and 2020) were the same and these should therefore be considered an elite group among all forensic practitioners. Supplementary Information The online version contains supplementary material available at 10.1007/s00414-020-02491-x.

Study objective Enterobacteriaceae resistant to ceftriaxone, mediated through extended-spectrum β-lactamases (ESBLs), commonly cause urinary tract infections worldwide, but have been less prevalent in North America. Current US rates are unknown. We determine Enterobacteriaceae antimicrobial resistance rates among US emergency department (ED) patients hospitalized for urinary tract infection. Methods We prospectively enrolled adults hospitalized for urinary tract infection from 11 geographically diverse university-affiliated hospital EDs during 2018 to 2019. Among participants with culture-confirmed infection, we evaluated prevalence of antimicrobial resistance, including that caused by ESBL-producing Enterobacteriaceae, resistance risk factors, and time to in vitro–active antibiotics. Results Of 527 total participants, 444 (84%) had cultures that grew Enterobacteriaceae; 89 of 435 participants (20.5%; 95% confidence interval 16.9% to 24.5%; 4.6% to 45.4% by site) whose isolates had confirmatory testing had bacteria that were ESBL producing. The overall prevalence of ESBL-producing Enterobacteriaceae infection among all participants with urinary tract infection was 17.2% (95% confidence interval 14.0% to 20.7%). ESBL-producing Enterobacteriaceae infection risk factors were hospital, long-term care, antibiotic exposure within 90 days, and a fluoroquinolone- or ceftriaxone-resistant isolate within 1 year. Enterobacteriaceae resistance rates for other antimicrobials were fluoroquinolone 32.3%, gentamicin 13.7%, amikacin 1.3%, and meropenem 0.3%. Ceftriaxone was the most common empirical antibiotic. In vitro–active antibiotics were not administered within 12 hours of presentation to 48 participants (53.9%) with ESBL-producing Enterobacteriaceae infection, including 17 (58.6%) with sepsis. Compared with other Enterobacteriaceae infections, ESBL infections were associated with longer time to in vitro–active treatment (17.3 versus 3.5 hours). Conclusion Among adults hospitalized for urinary tract infection in many US locations, ESBL-producing Enterobacteriaceae have emerged as a common cause of infection that is often not initially treated with an in vitro–active antibiotic.

Plant survival depends on adaptive mechanisms that constantly rely on signal recognition and transduction. The predominant class of signal discriminators is receptor kinases, with a vast member composition in plants. The transduction of signals occurs in part by a simple repertoire of heterotrimeric G proteins, with a core composed of α-, β-, and γ-subunits, together with a 7-transmembrane Regulator G Signaling (RGS) protein. With a small repertoire of G proteins in plants, phosphorylation by receptor kinases is critical in regulating the active state of the G-protein complex. This review describes the in vivo detected phosphosites in plant G proteins and conservation scores, and their in vitro corresponding kinases. Furthermore, recently described outcomes, including novel arrestin-like internalization of RGS and a non-canonical phosphorylation switching mechanism that drives G-protein plasticity, are discussed.