NPR1 is required for root colonization and the establishment of a mutualistic symbiosis between the beneficial bacterium Rhizobium radiobacter and barley.

Non-expressor of pathogenesis-related genes 1 (NPR1) is a key regulator of plant innate immunity and systemic disease resistance. The model for NPR1 function is based on experimental evidence obtained largely from dicots; however, this model does not fit all aspects of Poaceae family, which includes major crops such as wheat, rice and barley. In addition, there is little scientific data on NPR1's role in mutualistic symbioses. We assessed barley (Hordeum vulgare) HvNPR1 requirement during the establishment of mutualistic symbiosis between barley and beneficial Alphaproteobacterium Rhizobium radiobacter F4 (RrF4). Upon RrF4 root-inoculation, barley NPR1-knockdown (KD-hvnpr1) plants lost the typical spatiotemporal colonization pattern and supported less bacterial multiplication. Following RrF4 colonization, expression of salicylic acid marker genes were strongly enhanced in wild-type roots; whereas in comparison, KD-hvnpr1 roots exhibited little to no induction. Both basal and RrF4-induced root-initiated systemic resistance against virulent Blumeria graminis were impaired in leaves of KD-hvnpr1. Besides these immune-related differences, KD-hvnpr1 plants displayed higher root and shoot biomass than WT. However, RrF4-mediated growth promotion was largely compromised in KD-hvnpr1. Our results demonstrate a critical role for HvNPR1 in establishing a mutualistic symbiosis between a beneficial bacterium and a cereal crop.

Automatic precursor recognition and real-time forecasting of sudden explosive volcanic eruptions at Whakaari, New Zealand.

Sudden steam-driven eruptions strike without warning and are a leading cause of fatalities at touristic volcanoes. Recent deaths following the 2019 Whakaari eruption in New Zealand expose a need for accurate, short-term forecasting. However, current volcano alert systems are heuristic and too slowly updated with human input. Here, we show that a structured machine learning approach can detect eruption precursors in real-time seismic data streamed from Whakaari. We identify four-hour energy bursts that occur hours to days before most eruptions and suggest these indicate charging of the vent hydrothermal system by hot magmatic fluids. We developed a model to issue short-term alerts of elevated eruption likelihood and show that, under cross-validation testing, it could provide advanced warning of an unseen eruption in four out of five instances, including at least four hours warning for the 2019 eruption. This makes a strong case to adopt real-time forecasting models at active volcanoes.

RNA-based technologies for insect control in plant production.

RNA interference (RNAi) is a biological process in which small RNA (sRNA) molecules sequence-specifically silence gene expression at the transcriptional or post-transcriptional level, either by directing inhibitory chromatin modifications or by decreasing the stability or translation potential of the targeted mRNA. The trigger for gene silencing is double-stranded RNA (dsRNA) generated from an endogenous genomic locus or a foreign source, such as a transgene or virus. The process of gene silencing can be exploited in agriculture to control plant diseases and pests. Of the pests that impact crop yield (including nematodes, arthropods, rodents, snails, slugs and birds), insects constitute the largest and most diverse group. Here, we review the "pros" and "cons" of using RNAi technology mediated by dsRNA-expressing transgenic plants (host-induced gene silencing, HIGS) or direct application of chemically synthesized dsRNA to control plant-damaging insects. Rapid progress in elucidating RNAi mechanisms has led to the first commercial products on the market. Given the high potential of RNAi strategies, their use in agriculture, horticulture, and forestry will likely be extensive in the future. However, further studies are needed to improve the efficacy of RNAi-based plant protection strategies and to assess their associated safety risks.

A genome-wide screen for human salicylic acid (SA)-binding proteins reveals targets through which SA may influence development of various diseases.

Salicylic acid (SA) is the major metabolite and active ingredient of aspirin; both compounds reduce pain, fever, and inflammation. Despite over a century of research, aspirin/SA's mechanism(s) of action is still only partially understood. Here we report the results of a genome-wide, high-throughput screen to identify potential SA-binding proteins (SABPs) in human HEK293 cells. Following photo-affinity crosslinking to 4-azidoSA and immuno-selection with an anti-SA antibody, approximately 2,000 proteins were identified. Among these, 95 were enriched more than 10-fold. Pathway enrichment analysis with these 95 candidate SABPs (cSABPs) revealed possible involvement of SA in multiple biological pathways, including (i) glycolysis, (ii) cytoskeletal assembly and/or signaling, and (iii) NF-κB-mediated immune signaling. The two most enriched cSABPs, which corresponded to the glycolytic enzymes alpha-enolase (ENO1) and pyruvate kinase isozyme M2 (PKM2), were assessed for their ability to bind SA and SA's more potent derivative amorfrutin B1 (amoB1). SA and amoB1 bound recombinant ENO1 and PKM2 at low millimolar and micromolar concentrations, respectively, and inhibited their enzymatic activities in vitro. Consistent with these results, low millimolar concentrations of SA suppressed glycolytic activity in HEK293 cells. To provide insights into how SA might affect various human diseases, a cSABP-human disorder/disease network map was also generated.

Impact of body mass index on minimally invasive ventral hernia repair: an ACS-NSQIP analysis.

PURPOSE: Body mass index (BMI) ≥ 35 kg/m2 is a known independent risk factor for complications following open ventral hernia repair (VHR). We sought to examine the relationship between BMI and minimally invasive VHR. METHODS: The ACS-NSQIP database was queried for all patients age ≥ 18 years undergoing minimally invasive VHR (2005-2015). Patients were stratified into seven BMI classes: underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5-24.9), overweight (25-29.9), obese (30-34.5), severely obese (35-39.9), morbidly obese (40-49.9), and super obese (BMI ≥ 50), as well as by hernia type (reducible vs. strangulated) and time of repair (initial vs. recurrent). Multivariate logistic regression was employed to assess the risk of complication by BMI class. RESULTS: A total of 55,180 patients met inclusion criteria, and 61.4% had a BMI > 30 kg/m2. When stratified by BMI class, we found significant differences in age, gender, race, comorbidities, and pre-operative characteristics across groups. The overall complication rate was 4.0%, ranging from 3.0% for normal BMI patients, to 6.9% for patients with a BMI ≥ 50 kg/m2. Recurrent repairs and strangulated hernias both demonstrated higher complication rates. All complications (surgical and medical) were significantly associated with BMI class after adjustment (p < 0.0001). Patients with a BMI ≥ 50 kg/m2 had a 1.4 times greater risk for complications than patients with normal BMIs (18-24.9 kg/m2, p = 0.01). CONCLUSION: BMI ≥ 50 kg/m2 was determined to be an independent risk factor for surgical and medical complications after minimally invasive VHR.

Systemic Acquired Resistance and Salicylic Acid: Past, Present, and Future.

This article is part of the Distinguished Review Article Series in Conceptual and Methodological Breakthroughs in Molecular Plant-Microbe Interactions. Salicylic acid (SA) is a critical plant hormone that regulates numerous aspects of plant growth and development as well as the activation of defenses against biotic and abiotic stress. Here, we present a historical overview of the progress that has been made to date in elucidating the role of SA in signaling plant immune responses. The ability of plants to develop acquired immunity after pathogen infection was first proposed in 1933. However, most of our knowledge about plant immune signaling was generated over the last three decades, following the discovery that SA is an endogenous defense signal. During this timeframe, researchers have identified i) two pathways through which SA can be synthesized, ii) numerous proteins that regulate SA synthesis and metabolism, and iii) some of the signaling components that function downstream of SA, including a large number of SA targets or receptors. In addition, it has become increasingly evident that SA does not signal immune responses by itself but, rather, as part of an intricate network that involves many other plant hormones. Future efforts to develop a comprehensive understanding of SA-mediated immune signaling will therefore need to close knowledge gaps that exist within the SA pathway itself as well as clarify how crosstalk among the different hormone signaling pathways leads to an immune response that is both robust and optimized for maximal efficacy, depending on the identity of the attacking pathogen.

MORC Proteins: Novel Players in Plant and Animal Health.

Microrchidia (MORC) proteins comprise a family of proteins that have been identified in prokaryotes and eukaryotes. They are defined by two hallmark domains: a GHKL-type ATPase and an S5 fold. MORC proteins in plants were first discovered via a genetic screen for Arabidopsis mutants compromised for resistance to a viral pathogen. Subsequent studies expanded their role in plant immunity and revealed their involvement in gene silencing and transposable element repression. Emerging data suggest that MORC proteins also participate in pathogen-induced chromatin remodeling and epigenetic gene regulation. In addition, biochemical analyses recently demonstrated that plant MORCs have topoisomerase II (topo II)-like DNA modifying activities that may be important for their function. Interestingly, animal MORC proteins exhibit many parallels with their plant counterparts, as they have been implicated in disease development and gene silencing. In addition, human MORCs, like plant MORCs, bind salicylic acid and this inhibits some of their topo II-like activities. In this review, we will focus primarily on plant MORCs, although relevant comparisons with animal MORCs will be provided.

How does the multifaceted plant hormone salicylic acid combat disease in plants and are similar mechanisms utilized in humans?

Salicylic acid (SA) is an important plant hormone that regulates many aspects of plant growth and development, as well as resistance to (a)biotic stress. Efforts to identify SA effector proteins have revealed that SA binds to and alters the activity of multiple plant proteins-this represents a shift from the paradigm that hormones mediate their functions via one or a few receptors. SA and its derivatives also have multiple targets in animals; some of these proteins, like their plant counterparts, are associated with pathological processes. Together, these findings suggest that SA exerts its defense-associated effects in both kingdoms via a large number of targets.

Lymph node evaluation and survival after curative-intent resection of duodenal adenocarcinoma: A matched cohort study.

BACKGROUND: Lymph node (LN) metastasis in patients with duodenal adenocarcinoma is associated with poor prognosis; however, the optimal extent of LN assessment and the interaction between LN assessment and adjuvant systemic therapy is poorly understood. METHODS: Resected non-metastatic duodenal adenocarcinoma patients (n = 1743) were identified in the National Cancer Database (1998-2011). Logistic regression analysis identified covariates associated with LN metastasis. The influence of increasing LN cut-off points on overall survival (OS) was analysed using the log-rank test and Cox proportional hazards modelling. Adjuvant chemotherapy (AC) and surgery alone cohorts were matched (1:1) by propensity scores based on the likelihood of nodal metastasis or survival hazard on Cox modelling. OS in the matched cohort was compared by Kaplan-Meier estimates. RESULTS: LN metastases were present in 865 (49.6%) patients. Increasing LN assessment was associated with an increased likelihood of nodal involvement (P = 0.008). In node-negative patients, increasing LN assessment was associated with a decreased risk of death, with the largest actuarial survival differences observed for ≥15 LN (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.48-0.82, P = 0.001). In the propensity score-matched cohort of node-negative patients, AC was associated with non-significant improvements in 5-year actuarial (66.1% versus 58.7%, HR 0.79, 95% CI 0.53-1.18, P = 0.249), and did not vary by adequacy of LN counts (<15 LNs: HR 0.79, 95% CI 0.51-1.24, P = 0.305; ≥15 LNs: HR 0.90, 95% CI 0.35-2.30, P = 0.900). CONCLUSIONS: The extent of LN identification has prognostic significance in resected node-negative duodenal adenocarcinoma, but cannot be implicated in the selection of node-negative patients for AC.

Tracking the changes in virus taxonomy.

A database and website ( http://www.ictvonline.org/taxonomyReleases.asp ) have been established where the history of changes in virus taxonomy from 1971 to the present day can easily be traced. Each change is linked to a source document confirming the change or, for most changes since 2002, to the taxonomic proposal approved by the International Committee on Taxonomy of Viruses (ICTV).

Re-examining the BMI threshold for bariatric surgery in the USA.

BACKGROUND: The optimal BMI threshold above which gastric bypass surgery should be offered to obese patients is controversial. The objective of this study was to compare the impact of Roux-en-Y gastric bypass (RYGB) vs. diet and exercise (D&E) on life expectancy to find the BMI at which patients experience an improvement in their life expectancy by undergoing surgery. METHODS: A Markov state transition model was designed to implement a decision tree that simulated the lives of obese patients. Life expectancies following RYGB and 2 years of D&E were estimated and compared. Ten thousand patients' lives were simulated in each weight-loss intervention group in the model. In addition to base case analysis (45 kg/m(2) BMI pre-intervention), sensitivity analysis of initial BMI at the start of the study was completed. Markov model parameters were extracted from the literature. RESULTS: The impact of RYGB on survival relative to D&E depended on the patient's initial BMI. Compared to patients who underwent 2 years of "optimal" diet and exercise (7 % total body weight loss/year), RYGB improved long-term survival for patients above a BMI of 31.3 kg/m(2). CONCLUSIONS: Roux-en-Y gastric bypass can improve long-term survival for patients with class I obesity. This study suggests that RYGB should not be reserved solely for patients with class II or III obesity.

Genetic and pharmacokinetic determinants of response to transdermal nicotine in white, black, and Asian nonsmokers.

The aim of the study was to examine genetic, pharmacokinetic, and demographic factors that influence sensitivity to nicotine in never-smokers. Sixty never-smokers, balanced for gender and race (white, black, and Asian), wore 7-mg nicotine skin patches for up to 8 h. Serial plasma nicotine concentrations and subjective and cardiovascular effects were measured, and genetic variation in the CYP2A6 gene, encoding the primary enzyme responsible for nicotine metabolism, was assessed. Nicotine toxicity requiring patch removal developed in nine subjects and was strongly associated with rate of increase and peak concentrations of plasma nicotine. Toxicity and subjective and cardiovascular effects of nicotine were associated with the presence of reduced-function CYP2A6 alleles, presumably reflecting slow nicotine metabolic inactivation. This study has implications for understanding individual differences in responses to nicotine medications, particularly when they are used for treating medical conditions in nonsmokers, and possibly in vulnerability to developing nicotine dependence.

CYP2A6 genotype but not age determines cotinine half-life in infants and children.

The formation of cotinine, the main proximate metabolite and a biomarker of nicotine exposure, is mediated primarily by cytochrome P450 (CYP)2A6. Our aim was to determine whether higher cotinine levels in young children exposed to secondhand smoke (SHS) are a result of age-related differences in pharmacokinetics. Forty-nine participants, aged 2-84 months, received oral deuterium-labeled cotinine, with daily urine samples for up to 10 days for cotinine half-life measurement. DNA from saliva was used for CYP2A6 genotyping. The estimate of half-life using a mixed-effect model was 17.9 h (95% confidence interval: 16.5, 19.3), similar to that reported in adults. There was no statistically significant effect of sex, race, age, or weight. Children with normal-activity CYP2A6*1/*1 genotypes had a shorter half-life than those with one or two reduced-activity variant alleles. Our data suggest that higher cotinine levels in SHS-exposed young children as compared with adults are due to greater SHS exposure rather than to different cotinine pharmacokinetics.

SOS - too many signals for systemic acquired resistance?

Following pathogen infection, activation of systemic acquired resistance (SAR) in uninfected tissues requires transmission of a signal(s) from the infected tissue via the vasculature. Several candidates for this long-distance signal have been identified, including methyl salicylate (MeSA), an SFD1/GLY1-derived glycerol-3-phosphate (G3P)-dependent signal, the lipid-transfer protein DIR1, the dicarboxylic acid azelaic acid (AzA), the abietane diterpenoid dehydroabietinal (DA), jasmonic acid (JA), and the amino acid-derivative pipecolic acid (Pip). Some of these signals work cooperatively to activate SAR and/or regulate MeSA metabolism. However, Pip appears to activate SAR via an independent pathway that may impinge on these other signaling pathway(s) during de novo salicylic acid (SA) biosynthesis in the systemic tissue. Thus, a complex web of cross-interacting signals appears to activate SAR.

Splenic injury during colonoscopy--a complication that warrants urgent attention.

INTRODUCTION: Colonoscopy is a safe procedure that is performed routinely worldwide. There is, however, a small but significant risk of splenic injury that is often under-recognized. Due to a lack of awareness about this injury, the diagnosis may be delayed, which can lead to an increased risk of morbidity as well as mortality. This paper presents a comprehensive review of the medical literature on colonoscopy-associated splenic injury and describes the clinical presentation and management of this rare but potentially life-threatening complication. MATERIALS AND METHODS: A comprehensive literature search identified 102 patients worldwide, including patients from our experience, with splenic injury during colonoscopy. A meta-regression analysis was completed using a mixed generalized linear model for repeated measures to identify risk factors for this rare complication. RESULTS: A total of 75 articles were identified and 102 patients were studied. The majority of the papers were in English (92 %). Only 23.4 % of patients (26/102) were reported prior to the year 2000. Among the patients reported after the year 2000, the majority (84.2 %, 64/76) were reported after 2005. There were more females (76.5 %), median age was 65 years (range, 29-90 years), and most of the colonoscopies were performed without difficulty (66.6 %). Nearly 67 % of patients presented within 24 h of colonoscopy with complaints ranging from abdominal pain to dizziness. The most common symptom was left upper quadrant pain (58 %), and CT scan was found to be the most sensitive tool for diagnosis. Seventy-three patients underwent operative intervention; 96 % of these were treated with splenectomy. Hemoglobin drop of more than 3 gm/dL was identified as the only significant predictor of operative intervention. The overall mortality rate was 5 %. CONCLUSION: Splenic injury during colonoscopy is rare; however, it is associated with significant morbidity and mortality. Splenic injury warrants a high degree of clinical suspicion critical to prompt diagnosis, and early surgical consultation is warranted.

Multilayer vascular grafts based on collagen-mimetic proteins.

A major roadblock in the development of an off-the-shelf, small-caliber vascular graft is achieving rapid endothelialization of the conduit while minimizing the risk of thrombosis, intimal hyperplasia, and mechanical failure. To address this need, a collagen-mimetic protein derived from group A Streptococcus, Scl2.28 (Scl2), was conjugated into a poly(ethylene glycol) (PEG) hydrogel to generate bioactive hydrogels that bind to endothelial cells (ECs) and resist platelet adhesion. The PEG-Scl2 hydrogel was then reinforced with an electrospun polyurethane mesh to achieve suitable biomechanical properties. In the current study, initial evaluation of this multilayer design as a potential off-the-shelf graft was conducted. First, electrospinning parameters were varied to achieve composite burst pressure, compliance, and suture retention strength that matched reported values of saphenous vein autografts. Composite stability following drying, sterilization, and physiological conditioning under pulsatile flow was then demonstrated. Scl2 bioactivity was also maintained after drying and sterilization as indicated by EC adhesion and spreading. Evaluation of platelet adhesion, aggregation, and activation indicated that PEG-Scl2 hydrogels had minimal platelet interactions and thus appear to provide a thromboresistant blood contacting layer. Finally, evaluation of EC migration speed demonstrated that PEG-Scl2 hydrogels promoted higher migration speeds than PEG-collagen analogs and that migration speed was readily tuned by altering protein concentration. Collectively, these results indicate that this multilayer design warrants further investigation and may have the potential to improve on current synthetic options.

Trends and perioperative outcomes of inpatient antireflux surgery in the United States, 1993-2006.

Antireflux surgery is an effective treatment for gastroesophageal reflux disease, but postoperation complications and durability may be problematic. The objective of the study was to determine whether inpatient antireflux surgery continued to decline in the United States due to concerns about its long-term effectiveness and the popularity of gastric bypass surgery and to assess recent changes in its perioperative outcomes. Using the Nationwide Inpatient Sample, we identified adult patients undergoing inpatient antireflux surgery during 1993-2006 and compared the trends of inpatient antireflux surgery with inpatient gastric bypass surgery. Perioperative complications included laceration, splenectomy, transfusion, esophageal dilation, total parenteral nutrition, and infection. Inpatient antireflux surgery increased from 9173 in 1993 to 32 980 in 2000 (+260%) but then decreased to 19 668 in 2006 (-40%). Compared with 2000, patients undergoing inpatient antireflux surgery in 2006 were older (49.9 ± 32.4 vs. 54.6 ± 33.6 years) and had a longer length of stay (3.1 ± 10.0 vs. 3.7 ± 13.4 days), more complications (4.7% vs. 6.1%), and higher mortality (0.26% vs. 0.54%) (all P < 0.05). Compared with inpatient gastric bypass surgery, length of stay was longer and mortality was higher for inpatient antireflux surgery in 2006, but neither was significant controlling for age. In 2006, perioperative outcomes of inpatient antireflux surgery were better in high-volume hospitals (all P < 0.01). Inpatient antireflux surgery continued to decline in the United States from 2000 to 2006, concomitant with a dramatic increase in inpatient gastric bypass surgery. Older patient age and worsening perioperative outcomes for inpatient antireflux surgery suggest increased medical complexity and possibly a larger share of reoperations over time. Designating centers of excellence for antireflux surgery based on local expertise may improve outcomes.

Salicylic Acid biosynthesis and metabolism.

Salicylic acid (SA) has been shown to regulate various aspects of growth and development; it also serves as a critical signal for activating disease resistance in Arabidopsis thaliana and other plant species. This review surveys the mechanisms involved in the biosynthesis and metabolism of this critical plant hormone. While a complete biosynthetic route has yet to be established, stressed Arabidopsis appear to synthesize SA primarily via an isochorismate-utilizing pathway in the chloroplast. A distinct pathway utilizing phenylalanine as the substrate also may contribute to SA accumulation, although to a much lesser extent. Once synthesized, free SA levels can be regulated by a variety of chemical modifications. Many of these modifications inactivate SA; however, some confer novel properties that may aid in long distance SA transport or the activation of stress responses complementary to those induced by free SA. In addition, a number of factors that directly or indirectly regulate the expression of SA biosynthetic genes or that influence the rate of SA catabolism have been identified. An integrated model, encompassing current knowledge of SA metabolism in Arabidopsis, as well as the influence other plant hormones exert on SA metabolism, is presented.

Salicylic Acid, a multifaceted hormone to combat disease.

For more than 200 years, the plant hormone salicylic acid (SA) has been studied for its medicinal use in humans. However, its extensive signaling role in plants, particularly in defense against pathogens, has only become evident during the past 20 years. This review surveys how SA in plants regulates both local disease resistance mechanisms, including host cell death and defense gene expression, and systemic acquired resistance (SAR). Genetic studies reveal an increasingly complex network of proteins required for SA-mediated defense signaling, and this process is amplified by several regulatory feedback loops. The interaction between the SA signaling pathway and those regulated by other plant hormones and/or defense signals is also discussed.

Risks and benefits of nicotine to aid smoking cessation in pregnancy.

Cigarette smoking during pregnancy is the single largest modifiable risk for pregnancy-related morbidity and mortality in the US. Addiction to nicotine prevents many pregnant women who wish to quit smoking from doing so. The safety and efficacy of nicotine replacement therapy (NRT) for smoking cessation during pregnancy have not been well studied. Nicotine is classified by the US Food and Drug Administration as a Pregnancy Category D drug. Animal studies indicate that nicotine adversely affects the developing fetal CNS, and nicotine effects on the brain may be involved in the pathophysiology of sudden infant death syndrome (SIDS). It has been assumed that the cardiovascular effects of nicotine resulting in reduced blood flow to the placenta (uteroplacental insufficiency) is the predominant mechanism of the reproductive toxicity of cigarette smoking during pregnancy. Short term high doses of nicotine in pregnant animals do adversely affect the maternal and fetal cardiovascular systems. However, studies of the acute effects of NRT in pregnant humans indicate that nicotine alone has minimal effects upon the maternal and fetal cardiovascular systems. Cigarette smoking delivers thousands of chemicals, some of which are well documented reproductive toxins (e.g. carbon monoxide and lead). A myriad of cellular and molecular biological abnormalities have been documented in placentas, fetuses, and newborns of pregnant women who smoke. The cumulative abnormalities produced by the various toxins in cigarette smoke are probably responsible for the numerous adverse reproductive outcomes associated with smoking. It is doubtful that the reproductive toxicity of cigarette smoking is primarily related to nicotine. We recommend the following. Efficacy trials of NRT as adjunctive therapy for smoking cessation during pregnancy should be conducted. The initial dose of nicotine in NRT should be similar to the dose of nicotine that the pregnant woman received from smoking. Intermittent-use formulations of NRT (gum, spray, inhaler) are preferred because the total dose of nicotine delivered to the fetus will be less than with continuous-use formulations (transdermal patch). A national registry for NRT use during pregnancy should be created to prospectively collect obstetrical outcome data from NRT efficacy trials and from individual use. The goal of this registry would be to determine the safety of NRT use during pregnancy, especially with respect to uncommon outcomes such as placental abruption. Finally, our review of the data indicate that minimal amounts of nicotine are excreted into breast milk and that NRT can be safely used by breast-feeding mothers.