Summary
Processing of double‐stranded RNA precursors into small RNAs is an essential regulator of gene expression in plant development and stress response. Small RNA processing requires the combined ...activity of a functionally diverse group of molecular components. However, in most of the plant species, there are insufficient mutant resources to functionally characterize each encoding gene. Here, mutations in loci encoding protein machinery involved in small RNA processing in soya bean and Medicago truncatula were generated using the CRISPR/Cas9 and TAL‐effector nuclease (TALEN) mutagenesis platforms. An efficient CRISPR/Cas9 reagent was used to create a bi‐allelic double mutant for the two soya bean paralogous Double‐stranded RNA‐binding2 (GmDrb2a and GmDrb2b) genes. These mutations, along with a CRISPR/Cas9‐generated mutation of the M. truncatula Hua enhancer1 (MtHen1) gene, were determined to be germ‐line transmissible. Furthermore, TALENs were used to generate a mutation within the soya bean Dicer‐like2 gene. CRISPR/Cas9 mutagenesis of the soya bean Dicer‐like3 gene and the GmHen1a gene was observed in the T0 generation, but these mutations failed to transmit to the T1 generation. The irregular transmission of induced mutations and the corresponding transgenes was investigated by whole‐genome sequencing to reveal a spectrum of non‐germ‐line‐targeted mutations and multiple transgene insertion events. Finally, a suite of combinatorial mutant plants were generated by combining the previously reported Gmdcl1a, Gmdcl1b and Gmdcl4b mutants with the Gmdrb2ab double mutant. Altogether, this study demonstrates the synergistic use of different genome engineering platforms to generate a collection of useful mutant plant lines for future study of small RNA processing in legume crops.
There is a critical need for sensitive remote sensing approaches to monitor the parameters governing photosynthesis, at the temporal scales relevant to their natural dynamics. The photochemical ...reflectance index (PRI) and chlorophyll fluorescence (F) offer a strong potential for monitoring photosynthesis at local, regional, and global scales, however the relationships between photosynthesis and solar induced F (SIF) on diurnal and seasonal scales are not fully understood. This study examines how the fine spatial and temporal scale SIF observations relate to leaf level chlorophyll fluorescence metrics (i.e., PSII yield, YII and electron transport rate, ETR), canopy gross primary productivity (GPP), and PRI. The results contribute to enhancing the understanding of how SIF can be used to monitor canopy photosynthesis. This effort captured the seasonal and diurnal variation in GPP, reflectance, F, and SIF in the O2A (SIFA) and O2B (SIFB) atmospheric bands for corn (Zea mays L.) at a study site in Greenbelt, MD. Positive linear relationships of SIF to canopy GPP and to leaf ETR were documented, corroborating published reports. Our findings demonstrate that canopy SIF metrics are able to capture the dynamics in photosynthesis at both leaf and canopy levels, and show that the relationship between GPP and SIF metrics differs depending on the light conditions (i.e., above or below saturation level for photosynthesis). The sum of SIFA and SIFB (SIFA+B), as well as the SIFA+B yield, captured the dynamics in GPP and light use efficiency, suggesting the importance of including SIFB in monitoring photosynthetic function. Further efforts are required to determine if these findings will scale successfully to airborne and satellite levels, and to document the effects of data uncertainties on the scaling.
Background
The authors sought to identify the incidence, risk factors, and mortality impact of acute kidney injury (AKI) after general surgery using a large and representative national clinical data ...set.
Methods
The 2005-2006 American College of Surgeons-National Surgical Quality Improvement Program participant use data file is a compilation of outcome data from general surgery procedures performed in 121 US medical centers. The primary outcome was AKI within 30 days, defined as an increase in serum creatinine of at least 2 mg/dl or acute renal failure necessitating dialysis. A variety of patient comorbidities and operative characteristics were evaluated as possible predictors of AKI. A logistic regression full model fit was used to create an AKI model and risk index. Thirty-day mortality among patients with and without AKI was compared.
Results
Of 152,244 operations reviewed, 75,952 met the inclusion criteria, and 762 (1.0%) were complicated by AKI. The authors identified 11 independent preoperative predictors: age 56 yr or older, male sex, emergency surgery, intraperitoneal surgery, diabetes mellitus necessitating oral therapy, diabetes mellitus necessitating insulin therapy, active congestive heart failure, ascites, hypertension, mild preoperative renal insufficiency, and moderate preoperative renal insufficiency. The c statistic for a simplified risk index was 0.80 in the derivation and validation cohorts. Class V patients (six or more risk factors) had a 9% incidence of AKI. Overall, patients experiencing AKI had an eightfold increase in 30-day mortality.
Conclusions
Approximately 1% of general surgery cases are complicated by AKI. The authors have developed a robust risk index based on easily identified preoperative comorbidities and patient characteristics.
The authors sought to determine the incidence and risk factors for perioperative cardiac adverse events (CAEs) after noncardiac surgery using detailed preoperative and intraoperative hemodynamic ...data.
The authors conducted a prospective observational study at a single university hospital from 2002 to 2006. All American College of Surgeons-National Surgical Quality Improvement Program patients undergoing general, vascular, and urological surgery were included. The CAE outcome definition included cardiac arrest, non-ST elevation myocardial infarction, Q-wave myocardial infarction, and new clinically significant cardiac dysrhythmia within the first 30 postoperative days.
Four years of data demonstrated that of 7,740 noncardiac operations, 83 patients (1.1%) experienced a CAE within 30 days. Nine independent predictors were identified (P < or = 0.05): age > or = 68, body mass index > or = 30, emergent surgery, previous coronary intervention or cardiac surgery, active congestive heart failure, cerebrovascular disease, hypertension, operative duration > or = 3.8 h, and the administration of 1 or more units of packed red blood cells intraoperatively. The c-statistic of this model was 0.81 +/- 0.02. Univariate analysis demonstrated that high-risk patients experiencing a CAE were more likely to experience an episode of mean arterial pressure < 50 mmHg (6% vs. 24%, P = 0.02), experience an episode of 40% decrease in mean arterial pressure (26% vs. 53%, P = 0.01), and an episode of heart rate > 100 (22% vs. 34%, P = 0.05).
In comparison with current risk stratification indices, the inclusion of intraoperative elements improves the ability to predict a perioperative CAE after noncardiac surgery.
In 2015, an experiment was designed to investigate the distribution and variance of in winegrape flavonoids across the ripening phase in the Napa Valley. This Cabernet Sauvignon experiment was ...intended to evaluate the polyphenol differences across Napa Valley in order to understand parameters controlling “proanthocyanidin activity.” This method has shown promise in understanding proanthocyanidin (PA) astringency based on size distribution, pigmentation, conformation, and composition. Results from whole berry partial extractions showed that seed PA material was driving PA activity early in the ripening phase, while the formation of the pigmented polymer led to a decrease later in the growing season. Multivariate analysis showed that the main drivers of changes across the ripening phase were the molecular masses of PAs and the amount of pigmentation. Given the high amount of variability seen in the experiment between sites in such a small geographical area, the results suggest that manipulation of PA activity may be possible in the vineyard, perhaps explaining variations in wine mouthfeel attributes between locations. These results can be used to develop furthermore controlled experiments targeting the variables responsible for PA activity changes.
In patients with HCV genotype 1 infection and cirrhosis, the rate of sustained virologic response was 92% with three new antiviral agents plus ribavirin for 12 weeks and 96% with the same regimen for ...24 weeks. Two percent of patients discontinued treatment because of adverse events.
An estimated 184 million people worldwide have hepatitis C virus (HCV) infection,
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a leading cause of chronic liver disease and the leading indication for liver transplantation globally.
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,
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Approximately 25% of persons with HCV infection in the United States have cirrhosis, and this number is expected to rise to 37% by 2020.
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,
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Eradication of HCV with antiviral therapy reduces the risk of hepatic decompensation, hepatocellular carcinoma, and death from a liver-related cause or any cause.
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–
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Among patients with HCV infection and cirrhosis in whom peginterferon–ribavirin treatment has failed, rates of sustained virologic response to retreatment with interferon-containing regimens . . .
Condensed tannin extraction and stable color formation are two of the cornerstones of red wine production. Without condensed tannin, red wine would lack the tactile feeling of astringency, and ...without the formation of modified pigments, it would lack color stability for long-term aging. To understand how malvidin-3,5-diglucoside interacts with condensed tannin under nonoxidative conditions, an experiment was designed conducting model-wine skin extractions of Sauvignon blanc grapes harvested at various dates of maturity. Monomeric malvidin-3,5-diglucoside was isolated from color concentrate and added during these extractions. Following a 72 h extraction, solutions were evaluated for recovery of monomeric anthocyanins, skin tannin concentration, skin tannin extractability, and impact of anthocyanins on condensed tannin size. Anthocyanins showed a significant impact on the extraction of flavan-3-ol material in the early stages of ripening that declined in the latter stages of ripening. Furthermore, anthocyanins significantly decreased the size of the condensed tannin extracted. These results suggest that anthocyanins are not only enhancing the extractability of condensed tannin but also readily incorporating into the polymeric material, leading to a decrease in the average molecular mass of the condensed tannin polymer. The extent of reaction in 72 h suggests that the rate of interflavan bond cleavage may be higher than previously reported and merits closer scrutiny.
IMPORTANCE: Patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are at high risk for liver disease progression. However, interferon-based treatments for HCV ...infection have significant toxicities, limiting treatment uptake. OBJECTIVE: To assess the all-oral 3 direct-acting antiviral (3D) regimen of ombitasvir, paritaprevir (co-dosed with ritonavir paritaprevir/r), dasabuvir, and ribavirin in HCV genotype 1–infected adults with HIV-1 co-infection, including patients with cirrhosis. DESIGN, SETTING, AND PARTICIPANTS: TURQUOISE-I is a randomized, open-label study. Part 1a of this pilot study was conducted at 17 sites in the United States and Puerto Rico between September 2013 and August 2014 and included 63 patients with HCV genotype 1 and HIV-1 co-infection who were HCV treatment-naive or had history of prior treatment failure with peginterferon plus ribavirin therapy. The study allowed enrollment of patients, including those with cirrhosis, with a CD4+ count of 200/mm3 or greater or CD4+ percentage of 14% or more and plasma HIV-1 RNA suppressed while taking a stable atazanavir- or raltegravir-inclusive antiretroviral regimen. INTERVENTIONS: Ombitasvir/paritaprevir/r, dasabuvir, and ribavirin for 12 or 24 weeks of treatment as randomized. MAIN OUTCOMES AND MEASURES: The primary assessment was the proportion of patients with sustained virologic response (HCV RNA <25 IU/mL) at posttreatment week 12 (SVR12). RESULTS: Among patients receiving 12 or 24 weeks of 3D and ribavirin, SVR12 was achieved by 29 of 31 (94%; 95% CI, 79%-98%) and 29 of 32 patients (91%; 95% CI, 76%-97%), respectively. Of the 5 patients who did not achieve SVR, 1 withdrew consent, 2 had confirmed virologic relapse or breakthrough, and 2 patients had clinical history and phylogenetic evidence consistent with HCV reinfection. The most common treatment-emergent adverse events were fatigue (48%), insomnia (19%), nausea (18%), and headache (16%). Adverse events were generally mild, with none reported as serious or leading to discontinuation. No patient had a confirmed HIV-1 breakthrough of 200 copies/mL or greater during treatment. CONCLUSIONS AND RELEVANCE: In this open-label, randomized uncontrolled study, treatment with the all-oral, interferon-free 3D-plus-ribavirin regimen resulted in high SVR rates among patients co-infected with HCV genotype 1 and HIV-1 whether treated for 12 or 24 weeks. Further phase 3 studies of this regimen are warranted in patients with co-infection. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01939197
The authors sought to identify the incidence, risk factors, and mortality impact of acute kidney injury (AKI) after general surgery using a large and representative national clinical data set.
The ...2005-2006 American College of Surgeons-National Surgical Quality Improvement Program participant use data file is a compilation of outcome data from general surgery procedures performed in 121 US medical centers. The primary outcome was AKI within 30 days, defined as an increase in serum creatinine of at least 2 mg/dl or acute renal failure necessitating dialysis. A variety of patient comorbidities and operative characteristics were evaluated as possible predictors of AKI. A logistic regression full model fit was used to create an AKI model and risk index. Thirty-day mortality among patients with and without AKI was compared.
Of 152,244 operations reviewed, 75,952 met the inclusion criteria, and 762 (1.0%) were complicated by AKI. The authors identified 11 independent preoperative predictors: age 56 yr or older, male sex, emergency surgery, intraperitoneal surgery, diabetes mellitus necessitating oral therapy, diabetes mellitus necessitating insulin therapy, active congestive heart failure, ascites, hypertension, mild preoperative renal insufficiency, and moderate preoperative renal insufficiency. The c statistic for a simplified risk index was 0.80 in the derivation and validation cohorts. Class V patients (six or more risk factors) had a 9% incidence of AKI. Overall, patients experiencing AKI had an eightfold increase in 30-day mortality.
Approximately 1% of general surgery cases are complicated by AKI. The authors have developed a robust risk index based on easily identified preoperative comorbidities and patient characteristics.
Given the importance of young children's postures and movements to health and development, robust objective measures are required to provide high-quality evidence. This study aimed to systematically ...review the available evidence for objective measurement of young (0-5 years) children's posture and movement using machine learning and other algorithm methods on accelerometer data. From 1663 papers, a total of 20 papers reporting on 18 studies met the inclusion criteria. Papers were quality-assessed and data extracted and synthesised on sample, postures and movements identified, sensors used, model development, and accuracy. A common limitation of studies was a poor description of their sample data, yet over half scored adequate/good on their overall study design quality assessment. There was great diversity in all aspects examined, with evidence of increasing sophistication in approaches used over time. Model accuracy varied greatly, but for a range of postures and movements, models developed on a reasonable-sized (n > 25) sample were able to achieve an accuracy of >80%. Issues related to model development are discussed and implications for future research outlined. The current evidence suggests the rapidly developing field of machine learning has clear potential to enable the collection of high-quality evidence on the postures and movements of young children.
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