The auxin efflux carrier PIN1a regulates vascular patterning in cereal roots.

Barley (Hordeum vulgare) is an important global cereal crop and a model in genetic studies. Despite advances in characterising barley genomic resources, few mutant studies have identified genes controlling root architecture and anatomy, which plays a critical role in capturing soil resources. Our phenotypic screening of a TILLING mutant collection identified line TM5992 exhibiting a short-root phenotype compared with wild-type (WT) Morex background. Outcrossing TM5992 with barley variety Proctor and subsequent SNP array-based bulk segregant analysis, fine mapped the mutation to a cM scale. Exome sequencing pinpointed a mutation in the candidate gene HvPIN1a, further confirming this by analysing independent mutant alleles. Detailed analysis of root growth and anatomy in Hvpin1a mutant alleles exhibited a slower growth rate, shorter apical meristem and striking vascular patterning defects compared to WT. Expression and mutant analyses of PIN1 members in the closely related cereal brachypodium (Brachypodium distachyon) revealed that BdPIN1a and BdPIN1b were redundantly expressed in root vascular tissues but only Bdpin1a mutant allele displayed root vascular defects similar to Hvpin1a. We conclude that barley PIN1 genes have sub-functionalised in cereals, compared to Arabidopsis (Arabidopsis thaliana), where PIN1a sequences control root vascular patterning.

Overexpressing Vitamin C Defective 2 reduces fertility and alters Ca2+ signals in Arabidopsis pollen.

A potential strategy to mitigate oxidative damage in plants is to increase the abundance of antioxidants, such as ascorbate (i.e. vitamin C). In Arabidopsis (A. thaliana), a rate-limiting step in ascorbate biosynthesis is a phosphorylase encoded by Vitamin C Defective 2 (VTC2). To specifically overexpress VTC2 (VTC2 OE) in pollen, the coding region was expressed using a promoter from a gene with ∼150-fold higher expression in pollen, leading to pollen grains with an eight-fold increased VTC2 mRNA. VTC2 OE resulted in a near-sterile phenotype with a 50-fold decrease in pollen transmission efficiency and a five-fold reduction in the number of seeds per silique. In vitro assays revealed pollen grains were more prone to bursting (greater than two-fold) or produced shorter, morphologically abnormal pollen tubes. The inclusion of a genetically encoded Ca2+ reporter, mCherry-GCaMP6fast (CGf), revealed pollen tubes with altered tip-focused Ca2+ dynamics and increased bursting frequency during periods of oscillatory and arrested growth. Despite these phenotypes, VTC2 OE pollen failed to show expected increases in ascorbate or reductions in reactive oxygen species, as measured using a redox-sensitive dye or a roGFP2. However, mRNA expression analyses revealed greater than two-fold reductions in mRNA encoding two enzymes critical to biosynthetic pathways related to cell walls or glyco-modifications of lipids and proteins: GDP-d-mannose pyrophosphorylase (GMP) and GDP-d-mannose 3',5' epimerase (GME). These results support a model in which the near-sterile defects resulting from VTC2 OE in pollen are associated with feedback mechanisms that can alter one or more signaling or metabolic pathways critical to pollen tube growth and fertility.

A synchronized, large-scale field experiment using Arabidopsis thaliana reveals the significance of the UV-B photoreceptor UVR8 under natural conditions.

This study determines the functional role of the plant ultraviolet-B radiation (UV-B) photoreceptor, UV RESISTANCE LOCUS 8 (UVR8) under natural conditions using a large-scale 'synchronized-genetic-perturbation-field-experiment'. Laboratory experiments have demonstrated a role for UVR8 in UV-B responses but do not reflect the complexity of outdoor conditions where 'genotype × environment' interactions can mask laboratory-observed responses. Arabidopsis thaliana knockout mutant, uvr8-7, and the corresponding Wassilewskija wild type, were sown outdoors on the same date at 21 locations across Europe, ranging from 39°N to 67°N latitude. Growth and climatic data were monitored until bolting. At the onset of bolting, rosette size, dry weight, and phenolics and glucosinolates were quantified. The uvr8-7 mutant developed a larger rosette and contained less kaempferol glycosides, quercetin glycosides and hydroxycinnamic acid derivatives than the wild type across all locations, demonstrating a role for UVR8 under field conditions. UV effects on rosette size and kaempferol glycoside content were UVR8 dependent, but independent of latitude. In contrast, differences between wild type and uvr8-7 in total quercetin glycosides, and the quercetin-to-kaempferol ratio decreased with increasing latitude, that is, a more variable UV response. Thus, the large-scale synchronized approach applied demonstrates a location-dependent functional role of UVR8 under natural conditions.

The evolution of the duckweed ionome mirrors losses in structural complexity.

BACKGROUND AND AIMS: The duckweeds (Lemnaceae) consist of 36 species exhibiting impressive phenotypic variation, including the progressive evolutionary loss of a fundamental plant organ, the root. Loss of roots and reduction of vascular tissues in recently derived taxa occur in concert with genome expansions of ≤14-fold. Given the paired loss of roots and reduction in structural complexity in derived taxa, we focus on the evolution of the ionome (whole-plant elemental contents) in the context of these fundamental changes in body plan. We expect that progressive vestigiality and eventual loss of roots might have both adaptive and maladaptive consequences that are hitherto unknown. METHODS: We quantified the ionomes of 34 accessions in 21 species across all duckweed genera, spanning 70 Myr in this rapidly cycling plant (doubling times are as rapid as ~24 h). We related both micro- and macroevolutionary ionome contrasts to body plan remodelling and showed nimble microevolutionary shifts in elemental accumulation and exclusion in novel accessions. KEY RESULTS: We observed a robust directional trend in calcium and magnesium levels, decreasing from the ancestral representative Spirodela genus towards the derived rootless Wolffia, with the latter also accumulating cadmium. We also identified abundant within-species variation and hyperaccumulators of specific elements, with this extensive variation at the fine (as opposed to broad) scale. CONCLUSIONS: These data underscore the impact of root loss and reveal the very fine scale of microevolutionary variation in hyperaccumulation and exclusion of a wide range of elements. Broadly, they might point to trade-offs not well recognized in ionomes.

Societal shifts due to COVID-19 reveal large-scale complexities and feedbacks between atmospheric chemistry and climate change.

The COVID-19 global pandemic and associated government lockdowns dramatically altered human activity, providing a window into how changes in individual behavior, enacted en masse, impact atmospheric composition. The resulting reductions in anthropogenic activity represent an unprecedented event that yields a glimpse into a future where emissions to the atmosphere are reduced. Furthermore, the abrupt reduction in emissions during the lockdown periods led to clearly observable changes in atmospheric composition, which provide direct insight into feedbacks between the Earth system and human activity. While air pollutants and greenhouse gases share many common anthropogenic sources, there is a sharp difference in the response of their atmospheric concentrations to COVID-19 emissions changes, due in large part to their different lifetimes. Here, we discuss several key takeaways from modeling and observational studies. First, despite dramatic declines in mobility and associated vehicular emissions, the atmospheric growth rates of greenhouse gases were not slowed, in part due to decreased ocean uptake of CO2 and a likely increase in CH4 lifetime from reduced NO x emissions. Second, the response of O3 to decreased NO x emissions showed significant spatial and temporal variability, due to differing chemical regimes around the world. Finally, the overall response of atmospheric composition to emissions changes is heavily modulated by factors including carbon-cycle feedbacks to CH4 and CO2, background pollutant levels, the timing and location of emissions changes, and climate feedbacks on air quality, such as wildfires and the ozone climate penalty.

Psoas Muscle Area as a Predictor of Transcatheter Aortic Valve Implantation Outcomes.

BACKGROUND: Frailty is a well-recognised predictor of outcomes after transcatheter aortic valve implantation (TAVI). Psoas muscle area (PMA) is a surrogate marker for sarcopaenia and is a validated assessment tool for frailty. The objective of this study was to examine frailty as a predictor of outcomes in TAVI patients and assess the prognostic usefulness of adding PMA to established frailty assessments. METHODS: Frailty assessments were performed on 220 consecutive patients undergoing TAVI. These assessments used four markers (serum albumin, handgrip strength, gait speed, and a cognitive assessment), which were combined to form a composite frailty score. Preprocedural computed tomography scans were used to calculate cross-sectional PMA for each patient. The primary outcomes were all-cause mortality at 1-year and post-procedure length of hospital stay. RESULTS: Frailty status, as defined by the composite frailty score, was independently predictive of length of hospital stay (p=0.001), but not predictive of 1-year mortality (p=0.161). Albumin (p=0.036) and 5-metre walk test (p=0.003) were independently predictive of 1-year mortality. The PMA, when adjusted for gender, and normalised according to body surface area, was not predictive of 1-year mortality. Normalised PMA was associated with increased post-procedure length of stay within the female population (p=0.031). CONCLUSIONS: A low PMA is associated with increased length of hospital stay in female TAVI patients but does not provide additional predictive value over traditional frailty scores. The PMA was not shown to correlate with TAVI-related complications or 1-year mortality.

Repurposing FDA-approved drugs as inhibitors of therapy-induced invadopodia activity in glioblastoma cells.

Glioblastoma (GBM) is the most prevalent primary central nervous system tumour in adults. The lethality of GBM lies in its highly invasive, infiltrative, and neurologically destructive nature resulting in treatment failure, tumour recurrence and death. Even with current standard of care treatment with surgery, radiotherapy and chemotherapy, surviving tumour cells invade throughout the brain. We have previously shown that this invasive phenotype is facilitated by actin-rich, membrane-based structures known as invadopodia. The formation and matrix degrading activity of invadopodia is enhanced in GBM cells that survive treatment. Drug repurposing provides a means of identifying new therapeutic applications for existing drugs without the need for discovery or development and the associated time for clinical implementation. We investigate several FDA-approved agents for their ability to act as both cytotoxic agents in reducing cell viability and as 'anti-invadopodia' agents in GBM cell lines. Based on their cytotoxicity profile, three agents were selected, bortezomib, everolimus and fludarabine, to test their effect on GBM cell invasion. All three drugs reduced radiation/temozolomide-induced invadopodia activity, in addition to reducing GBM cell viability. These drugs demonstrate efficacious properties warranting further investigation with the potential to be implemented as part of the treatment regime for GBM.

Latitudinal gradient in species diversity provides high niche opportunities for a range-expanding phytophagous insect.

When species undergo poleward range expansions in response to anthropogenic change, they likely encounter less diverse communities in new locations. If low diversity communities provide weak biotic interactions, such as reduced competition or predation, range-expanding species may experience high niche opportunities. Here, we investigated if oak gall wasp communities follow a latitudinal diversity gradient (LDG) and if lower diversity communities provide weaker interactions at the poles for a range-expanding community member, Neuroterus saltatorius. We performed systematic surveys of gall wasps on a dominant oak, Quercus garryana, throughout most of its range, from northern California to Vancouver Island, British Columbia. On 540 trees at 18 sites, we identified 23 oak gall wasp morphotypes in three guilds (leaf detachable, leaf integral, and stem galls). We performed regressions between oak gall wasp diversity, latitude, and other abiotic (e.g. temperature) and habitat (e.g. oak patch size) factors to reveal if gall wasp communities followed an LDG. To uncover patterns in local interactions, we first performed partial correlations of gall wasp morphotype occurrences on trees within regions). We then performed regressions between abundances of co-occurring gall wasps on trees to reveal if interactions are putatively competitive or antagonistic. Q. garryana-gall wasp communities followed an LDG, with lower diversity at higher latitudes, particularly with a loss of detachable leaf gall morphotypes. Detachable leaf gall wasps, including the range-expanding species, co-occurred most on trees, with weak co-occurrences on trees in the northern expanded region. Abundances of N. saltatorius and detachable and integral leaf galls co-occurring on trees were negatively related, suggesting antagonistic interactions. Overall, we found that LDGs create communities with weaker associations at the poles that might facilitate ecological release in a range-expanding community member. Given the ubiquity of LDGs in nature, poleward range-expanding species are likely moving into low diversity communities. Yet, understanding if latitudinal diversity pattern provides weak biotic interactions for range-expanding species is not well explored. Our large-scale study documenting diversity in a related community of phytophagous insects that co-occur on a host plant reveals that LDGs create high niche opportunities for a range-expanding community member. Biogeographical patterns in diversity and species interactions are likely important mechanisms contributing to altered biotic interactions under range-expansions.

Cuando las especies se expanden hacia los polos en respuesta al cambio antropogénico, es probable que las encuentren comunidades menos diversas en sus nuevos lugares. Si las comunidades de baja diversidad proporcionan interacciones bióticas débiles, como competencia reducida o depredación, las especies que se expanden pueden tener 'oportunidades de alto nicho'. Aquí, investigamos si las comunidades de avispas de las agallas muestran un gradiente de diversidad latitudinal (LDG) y si las comunidades de menor diversidad proporcionan interacciones antagónicas más débiles en los polos para las comunidades que se expanden. Específicamente, investigamos estas relaciones en la comunidad de Neuroterus saltatorius. Realizamos estudios sistemáticos de las avispas de las agallas en un roble dominante, Quercus garryana en la mayor parte de su área de distribución, desde el norte de California hasta la isla de Vancouver, en la Columbia Británica. Sobre 540 árboles en 18 sitios y 6 regiones, nos identificamos 23 mofotipos de avispas de las agallas en tres gremios (hoja desmontable, hoja integral y agallas del tallo). Ejecutamos regresiones entre la diversidad de avispas de las agallas, la latitud, y otros factores abióticos (p. ej., temperatura) y de hábitat (p. ej., tamaño del parche de roble) para revelar si las comunidades de avispas de las agallas siguieron un LDG. Para descubrir tendencias en las interacciones locales, primero ejecutamos correlaciones parciales de ocurrencias de morfotipos de avispas de las agallas en árboles dentro de las regiones. Luego ejecutamos regresiones entre las coocurrencias de las abundancias deavispas de las agallas en los árboles para revelar si las interacciones son supuestamente competitivas o antagónicas. Las comunidades de avispas Q. garryana-gall, siguieron un LDG, con menor diversidad en latitudes más altas, particularmente con una pérdida de morfotipos de agallas de hoja desmontable. Las avispas de las agallas de las hojas desprendibles, incluidas a las especies que se expanden su hábitat, se encontraron en sobre todos los árboles, con coocurrencias débiles en los árboles de la región expandida del norte. Las coocurrencias de las las abundancias de N. saltatorius,las agallas foliares desmontables, e agallas integrales en los árboles se relacionaron negativamente, lo que sugiere interacciones antagónicas. En general, encontramos que los LDG crean comunidades con asociaciones más débiles en los polos que podrían facilitar la liberación ecológica en un miembro de la comunidad que se expanden. Debido de la ubicuidad de los LDG en la naturaleza, es probable que las especies que se expanden hacia los polos se estén trasladando a comunidades de baja diversidad. Sin embargo, no se explora bien la comprensión de si las tendenciasde diversidad latitudinal proporcionan interacciones bióticas débiles para las especies que se expanden. Nuestro estudio degran escala documenta la diversidad en una comunidad relacionada de insectos fitófagos que coexisten en una planta hospedante. Como resultado, revela que los LDG pueden crear oportunidades de grandes nichos para un miembro de la comunidad que se expande. Los patrones biogeográficos en la diversidad y las interacciones entre especies son probablemente mecanismos importantes que contribuyen a las interacciones bióticas alteradas bajo la expansión del hábitat.

Hypoxia-induced switch in SNAT2/SLC38A2 regulation generates endocrine resistance in breast cancer.

Tumor hypoxia is associated with poor patient outcomes in estrogen receptor-α-positive (ERα+) breast cancer. Hypoxia is known to affect tumor growth by reprogramming metabolism and regulating amino acid (AA) uptake. Here, we show that the glutamine transporter, SNAT2, is the AA transporter most frequently induced by hypoxia in breast cancer, and is regulated by hypoxia both in vitro and in vivo in xenografts. SNAT2 induction in MCF7 cells was also regulated by ERα, but it became predominantly a hypoxia-inducible factor 1α (HIF-1α)-dependent gene under hypoxia. Relevant to this, binding sites for both HIF-1α and ERα overlap in SNAT2's cis-regulatory elements. In addition, the down-regulation of SNAT2 by the ER antagonist fulvestrant was reverted in hypoxia. Overexpression of SNAT2 in vitro to recapitulate the levels induced by hypoxia caused enhanced growth, particularly after ERα inhibition, in hypoxia, or when glutamine levels were low. SNAT2 up-regulation in vivo caused complete resistance to antiestrogen and, partially, anti-VEGF therapies. Finally, high SNAT2 expression levels correlated with hypoxia profiles and worse outcome in patients given antiestrogen therapies. Our findings show a switch in the regulation of SNAT2 between ERα and HIF-1α, leading to endocrine resistance in hypoxia. Development of drugs targeting SNAT2 may be of value for a subset of hormone-resistant breast cancer.

Phospholipid membranes drive abdominal aortic aneurysm development through stimulating coagulation factor activity.

Abdominal aortic aneurysm (AAA) is an inflammatory vascular disease with high mortality and limited treatment options. How blood lipids regulate AAA development is unknown. Here lipidomics and genetic models demonstrate a central role for procoagulant enzymatically oxidized phospholipids (eoxPL) in regulating AAA. Specifically, through activating coagulation, eoxPL either promoted or inhibited AAA depending on tissue localization. Ang II administration to ApoE-/- mice increased intravascular coagulation during AAA development. Lipidomics revealed large numbers of eoxPL formed within mouse and human AAA lesions. Deletion of eoxPL-generating enzymes (Alox12 or Alox15) or administration of the factor Xa inhibitor rivaroxaban significantly reduced AAA. Alox-deficient mice displayed constitutively dysregulated hemostasis, including a consumptive coagulopathy, characterized by compensatory increase in prothrombotic aminophospholipids (aPL) in circulating cell membranes. Intravenously administered procoagulant PL caused clotting factor activation and depletion, induced a bleeding defect, and significantly reduced AAA development. These data suggest that Alox deletion reduces AAA through diverting coagulation away from the vessel wall due to eoxPL deficiency, instead activating clotting factor consumption and depletion in the circulation. In mouse whole blood, ∼44 eoxPL molecular species formed within minutes of clot initiation. These were significantly elevated with ApoE-/- deletion, and many were absent in Alox-/- mice, identifying specific eoxPL that modulate AAA. Correlation networks demonstrated eoxPL belonged to subfamilies defined by oxylipin composition. Thus, procoagulant PL regulate AAA development through complex interactions with clotting factors. Modulation of the delicate balance between bleeding and thrombosis within either the vessel wall or circulation was revealed that can either drive or prevent disease development.

Impact of Surgical and Transcatheter Aortic Valve Replacement on Frailty Score.

OBJECTIVE: Frailty is common in the aortic stenosis (AS) population and impacts outcomes after both transcatheter and surgical aortic valve replacement (TAVR and sAVR, respectively). Frailty can significantly impact the decision regarding the suitability of a patient for aortic valve intervention, with frail patients often excluded. Since many frailty tools use indicators which may be influenced by AS itself, some of which are subjectively symptom driven, we sought to determine the impact of intervention on frailty scores. METHODS: A prospective, observational cohort study included patients being assessed for aortic valve (AV) intervention with either TAVR or sAVR due to severe aortic stenosis. Patients were assessed for symptoms at baseline, and 1- and 6-months post intervention subjectively, using the New York Heart Association (NYHA) class and the Kansas City Cardiomyopathy Questionnaire (KCCQ), and objectively, using a 6-minute walk test (6MWT). These were compared with frailty at baseline and final review using the Fried Frailty Scale (FFS). RESULTS AND CONCLUSIONS: Sixty-six (66) patients completed pre- and post-intervention reviews. The mean FFS score was significantly lower, indicating less frailty, at 6 months relative to pre procedure (1.18 vs 1.73, p=0.002). This correlated with the change in symptoms (p<0.001). Between intervention groups, the final mean FFS of both groups decreased significantly, with TAVR to 1.33 (p=0.030) and sAVR to 0.8 (p=0.015). There was no difference in the degree of improvement between interventions (p=0.517). Aortic valve intervention improves frailty scores in both TAVR and sAVR treated patients.

Spatial co-localisation of extreme weather events: a clear and present danger.

Extreme weather events have become a dominant feature of the narrative surrounding changes in global climate with large impacts on ecosystem stability, functioning and resilience; however, understanding of their risk of co-occurrence at the regional scale is lacking. Based on the UK Met Office's long-term temperature and rainfall records, we present the first evidence demonstrating significant increases in the magnitude, direction of change and spatial co-localisation of extreme weather events since 1961. Combining this new understanding with land-use data sets allowed us to assess the likely consequences on future agricultural production and conservation priority areas. All land-uses are impacted by the increasing risk of at least one extreme event and conservation areas were identified as the hotspots of risk for the co-occurrence of multiple event types. Our findings provide a basis to regionally guide land-use optimisation, land management practices and regulatory actions preserving ecosystem services against multiple climate threats.

trans-3-Methylglutaconyl CoA isomerization-dependent protein acylation.

3-methylglutaconic (3MGC) aciduria is associated with a growing number of discrete inborn errors of metabolism. Herein, an antibody-based approach to detection/quantitation of 3MGC acid has been pursued. When trans-3MGC acid conjugated keyhole limpet hemocyanin (KLH) was inoculated into rabbits a strong immune response was elicited. Western blot analysis provided evidence that immune serum, but not pre-immune serum, recognized 3MGC-conjugated bovine serum albumin (BSA). In competition ELISAs using isolated immune IgG, the limit of detection for free trans-3MGC acid was compared to that for cis-3MGC acid and four structurally related short-chain dicarboxylic acids. Surprisingly, cis-3MGC acid yielded a much lower limit of detection (∼0.1 mg/ml) than trans-3MGC acid (∼1.0 mg/ml) while all other dicarboxylic acids tested were poor competitors. The data suggest trans-3MGC- isomerized during, or after, conjugation to KLH such that the immunogen was actually comprised of KLH harboring a mixture of cis- and trans-3MGC haptens. To investigate this unexpected isomerization reaction, trans-3MGC CoA was prepared and incubated at 37 °C in the presence of BSA. Evidence was obtained that non-enzymatic isomerization of trans-3MGC CoA to cis-3MGC CoA precedes intramolecular catalysis to form cis-3MGC anhydride plus CoASH. Anhydride-dependent acylation of BSA generated 3MGCylated BSA, as detected by anti-3MGC immunoblot. The results presented provide an explanation for the unanticipated detection of 3MGCylated proteins in a murine model of primary 3MGC aciduria. Furthermore, non-enzymatic hydrolysis of cis-3MGC anhydride represents a potential source of cis-3MGC acid found in urine of subjects with 3MGC aciduria.

The spectrum of Epstein-Barr virus infections of the central nervous system after organ transplantation.

BACKGROUND: Epstein-Barr virus (EBV)-related neurologic complications have a diverse presentation in transplant recipients, creating diagnostic and therapeutic challenges for clinicians. In this case series, we report unique manifestations of EBV related neurologic complications following solid organ transplant and highlight pitfalls in management. CASE PRESENTATIONS: A retrospective search of the electronic medical record of all patients from January 2015 to December 2020 who underwent solid organ transplantation and had central nervous system complications as determined by ICD-10 codes were included. Three patients with unique manifestation of EBV-related neurologic complications after liver transplantation were identified. The first was a 52-year-old man with a live-donor liver transplant 11 years prior for Budd-Chiari syndrome presented with several weeks of headache and several lesions on brain MRI; he was diagnosed with primary central nervous system post-transplant lymphoproliferative disorder. The second patient was a 63-year-old man with a deceased-donor liver transplant 16 years prior for alpha-1-antitrypsin deficiency and was found to have a stroke; he was diagnosed with EBV encephalitis. The final patient was a 75-year-old woman with a deceased-donor liver transplant six years prior for primary biliary cirrhosis who presented with four months of gait instability; she was diagnosed with EBV myelitis. A review of the literature was performed to supplement description of the different diseases. CONCLUSIONS: EBV-related central nervous infection in post-transplant patients can manifest in a variety of neurologic syndromes, which can be challenging to diagnose. Careful correlation of clinical, pathologic, and radiologic findings and a high index of suspicion are crucial in identification and appropriate management.

Unexpected slowdown of US pollutant emission reduction in the past decade.

Ground and satellite observations show that air pollution regulations in the United States (US) have resulted in substantial reductions in emissions and corresponding improvements in air quality over the last several decades. However, large uncertainties remain in evaluating how recent regulations affect different emission sectors and pollutant trends. Here we show a significant slowdown in decreasing US emissions of nitrogen oxides (NO x ) and carbon monoxide (CO) for 2011-2015 using satellite and surface measurements. This observed slowdown in emission reductions is significantly different from the trend expected using US Environmental Protection Agency (EPA) bottom-up inventories and impedes compliance with local and federal agency air-quality goals. We find that the difference between observations and EPA's NO x emission estimates could be explained by: (i) growing relative contributions of industrial, area, and off-road sources, (ii) decreasing relative contributions of on-road gasoline, and (iii) slower than expected decreases in on-road diesel emissions.

Controlled comparisons between soil and hydroponic systems reveal increased water use efficiency and higher lycopene and ß-carotene contents in hydroponically grown tomatoes.

There are many different types of systems used to grow food that are distinguished by ideology or the technology used. It is often difficult to directly compare yield and quality in different growth systems due to the complicated interactions between genotype, physiology and environment. Many published comparisons do not identify and acknowledge confounding factors. However, there is urgency to undertake controlled comparisons to identify the most efficient and effective food production systems, because the world faces considerable challenges to food supply with population rise, ongoing environmental degradation and the threat of climatic change. Here we compared soil with two hydroponic growth systems, drip irrigation and deep-water culture (DWC). It is often claimed that such systems differ in water use, yield and crop quality; however, such comparisons are often confounded by assessing plant and system parameters in different growth environments or where factors that are difficult to standardise between systems, such as nutrient status, are not controlled. We grew tomato (Solanum lycopersicum L.) in the three growth systems in two replicated experiments, in either a polytunnel or glasshouse. We controlled and monitored water use and nutrient levels across all systems as different fertilizer applications can influence the nutritional values of produce. Plants in the two hydroponic systems transpired less water and were more water-efficient with a lower product water use than plants grown in soil. Fruit yield was similar and total soluble solids and sugar levels were not significantly different between the three growing systems. However, levels of lycopene and ß-carotene were either similar or significantly higher in DWC compared to growth systems using soil or drip irrigation. Our results identify hydroponic systems as more water use efficient with DWC also capable of producing higher quality produce.

Case report describing late balloon dilatation as a treatment for paravalvular leak with intuity elite rapid deployment valve.

Use of sutureless bioprostheses for aortic valve replacement has increased in recent years as compared to conventional prostheses, though with the potential issue of paravalvular leak, which requires close follow-up. We present this case report describing the successful treatment of paravalvular leak in a 65 year old man, who had NYHA class III symptoms post implantation of a 21 mm Intuity Elite rapid deployment bioprosthesis (Edwards Lifesciences, Irvine, CA). Diagnosis was established using TTE, TOE, and Cardiac MRI. Performing balloon dilatation using an Atlas Gold balloon (BARD Peripheral Vascular Inc., Tempe, AZ) treated the likely inadequate expansion of the subvalvular stent, leading to significant reduction in the paravalvular leak. At one month follow-up patient reported complete resolution of his symptoms. Successful percutaneous treatment of paravalvular leak following implantation of rapid deployment sutureless bioprosthesis provides a new treatment strategy for these patients; this strategy requires further validation.

Effect of Balloon Aortic Valvuloplasty on Mortality in Patients With Severe Aortic Stenosis Prior to Conservative Treatment and Surgical or Transcatheter Aortic Valve Replacement.

BACKGROUND: Outcomes following an initial strategy of balloon aortic valvuloplasty (BAV) prior to medical therapy or intervention with surgical or transcatheter aortic valve replacement (SAVR or TAVR) are unclear in the modern transcatheter intervention era. METHODS: A retrospective, observational cohort study of the echocardiography, cardiothoracic surgery and TAVR databases between 1 January 2006 and 31 December 2016 was performed to compare outcomes between all patients with severe aortic stenosis (AS) treated with or without BAV prior to medical or invasive therapy. RESULTS: 3,142 patients were available for analysis. 223 BAV treated patients had lower mortality relative to medically treated patients, particularly early (20.1% v. 7.6% at 6 months, 58.1% v. 52.5% at 5 years). Over 5 years, the adjusted hazard ratio (HR) was 0.62 (95% CI 0.48-0.80, p < 0.001). Compared with 630 patients proceeding directly to intervention, 75 patients receiving BAV experienced a higher mortality (HR = 2.76, 95% CI 2.07-3.66, p < 0.001). No subsequent excess perioperative mortality was observed with BAV compared with those receiving surgery directly (HR = 1.45, 95% CI 0.91-2.31, p = 0.117). CONCLUSIONS: The risk associated with BAV is low, and improves mortality compared with medical therapy. Balloon aortic valvuloplasty treated patients have poorer outcomes, but treatment with BAV does not increase perioperative mortality and may lessen it.

Quantifying the Impact of Atmospheric Transport Uncertainty on CO2 Surface Flux Estimates.

We show that transport differences between two commonly used global chemical transport models, GEOS-Chem and TM5, lead to systematic space-time differences in modeled distributions of carbon dioxide and sulfur hexafluoride. The distribution of differences suggests inconsistencies between the transport simulated by the models, most likely due to the representation of vertical motion. We further demonstrate that these transport differences result in systematic differences in surface CO2 flux estimated by a collection of global atmospheric inverse models using TM5 and GEOS-Chem and constrained by in situ and satellite observations. While the impact on inferred surface fluxes is most easily illustrated in the magnitude of the seasonal cycle of surface CO2 exchange, it is the annual carbon budgets that are particularly relevant for carbon cycle science and policy. We show that inverse model flux estimates for large zonal bands can have systematic biases of up to 1.7 PgC/year due to large-scale transport uncertainty. These uncertainties will propagate directly into analysis of the annual meridional CO2 flux gradient between the tropics and northern midlatitudes, a key metric for understanding the location, and more importantly the processes, responsible for the annual global carbon sink. The research suggests that variability among transport models remains the largest source of uncertainty across global flux inversion systems and highlights the importance both of using model ensembles and of using independent constraints to evaluate simulated transport.

A Retrospective Analysis of Treatment and Clinical Outcomes among Patients with Methicillin-Susceptible Staphylococcus aureus Bloodstream Isolates Possessing Detectable mecA by a Commercial PCR Assay Compared to Patients with Methicillin-Resistant Staphylococcus aureus Bloodstream Isolates.

mecA-positive Staphylococcus aureus isolates phenotypically susceptible to cefoxitin (mecA-methicillin-sensitive S. aureus [MSSA]) have been identified. We describe the treatment and outcomes among patients with mecA-MSSA bloodstream infections (BSI) and MRSA BSI matched 1:1 for age, BSI origin, and BSI type (n = 17 per group). Compared to MRSA BSI patients, mecA-MSSA BSI patients more often experienced clinical failure (58.8% and 11.8%, P = 0.010), driven largely by persistent bacteremia (35.3% and 11.8%). mecA-MSSA BSI patients may be at higher risk for poor clinical outcomes.