Bread wheat (Triticum aestivum) has a large, complex and hexaploid genome consisting of A, B and D homoeologous chromosome sets. Therefore each wheat gene potentially exists as a trio of A, B and D ...homoeoloci, each of which may contribute differentially to wheat phenotypes. We describe a novel approach combining wheat cytogenetic resources (chromosome substitution 'nullisomic-tetrasomic' lines) with next generation deep sequencing of gene transcripts (RNA-Seq), to directly and accurately identify homoeologue-specific single nucleotide variants and quantify the relative contribution of individual homoeoloci to gene expression.
We discover, based on a sample comprising ~5-10% of the total wheat gene content, that at least 45% of wheat genes are expressed from all three distinct homoeoloci. Most of these genes show strikingly biased expression patterns in which expression is dominated by a single homoeolocus. The remaining ~55% of wheat genes are expressed from either one or two homoeoloci only, through a combination of extensive transcriptional silencing and homoeolocus loss.
We conclude that wheat is tending towards functional diploidy, through a variety of mechanisms causing single homoeoloci to become the predominant source of gene transcripts. This discovery has profound consequences for wheat breeding and our understanding of wheat evolution.
Scant information exists about the epidemiological characteristics and outcome of patients in the intensive care unit (ICU) at risk of acute respiratory distress syndrome (ARDS) and how ventilation ...is managed in these individuals. We aimed to establish the epidemiological characteristics of patients at risk of ARDS, describe ventilation management in this population, and assess outcomes compared with people at no risk of ARDS.
PRoVENT (PRactice of VENTilation in critically ill patients without ARDS at onset of ventilation) is an international, multicentre, prospective study undertaken at 119 ICUs in 16 countries worldwide. All patients aged 18 years or older who were receiving mechanical ventilation in participating ICUs during a 1-week period between January, 2014, and January, 2015, were enrolled into the study. The Lung Injury Prediction Score (LIPS) was used to stratify risk of ARDS, with a score of 4 or higher defining those at risk of ARDS. The primary outcome was the proportion of patients at risk of ARDS. Secondary outcomes included ventilatory management (including tidal volume V
expressed as mL/kg predicted bodyweight PBW, and positive end-expiratory pressure PEEP expressed as cm H
O), development of pulmonary complications, and clinical outcomes. The PRoVENT study is registered at ClinicalTrials.gov, NCT01868321. The study has been completed.
Of 3023 patients screened for the study, 935 individuals fulfilled the inclusion criteria. Of these critically ill patients, 282 were at risk of ARDS (30%, 95% CI 27-33), representing 0·14 cases per ICU bed over a 1-week period. V
was similar for patients at risk and not at risk of ARDS (median 7·6 mL/kg PBW IQR 6·7-9·1 vs 7·9 mL/kg PBW 6·8-9·1; p=0·346). PEEP was higher in patients at risk of ARDS compared with those not at risk (median 6·0 cm H
O IQR 5·0-8·0 vs 5·0 cm H
O 5·0-7·0; p<0·0001). The prevalence of ARDS in patients at risk of ARDS was higher than in individuals not at risk of ARDS (19/260 7% vs 17/556 3%; p=0·004). Compared with individuals not at risk of ARDS, patients at risk of ARDS had higher in-hospital mortality (86/543 16% vs 74/232 32%; p<0·0001), ICU mortality (62/533 12% vs 66/227 29%; p<0·0001), and 90-day mortality (109/653 17% vs 88/282 31%; p<0·0001). V
did not differ between patients who did and did not develop ARDS (p=0·471 for those at risk of ARDS; p=0·323 for those not at risk).
Around a third of patients receiving mechanical ventilation in the ICU were at risk of ARDS. Pulmonary complications occur frequently in patients at risk of ARDS and their clinical outcome is worse compared with those not at risk of ARDS. There is potential for improvement in the management of patients without ARDS. Further refinements are needed for prediction of ARDS.
None.
AIM: Some regions donate more invaders from particular taxonomic and functional groups than they receive. We demonstrate a particularly striking donor–recipient asymmetry in invasion ecology in ...grasses. Specifically, we explore whether low numbers of invasive grasses in South Africa can be explained by sampling biases, introduction dynamics, species traits or invasibility of ecosystems. LOCATION: South Africa, Australia, Chile, Europe and the USA. METHODS: We tested for a donor–recipient asymmetry using lists of native and non‐native grasses in five regions across the globe. Then, using distribution, trait and environmental data, we tested whether regions differed in: (1) herbarium sampling effort; (2) introduction dynamics of non‐native grasses (primary uses, area of origin and minimum residence time of non‐native grasses); (3) traits of native and non‐native grasses (leaf size, height, life history, growth form, C₃:C₄ ratio and taxonomic placement); and (4) fire frequency. RESULTS: South Africa has fewer invasive grasses, and fewer widespread invasive grasses, than other regions; while grasses native to South Africa are much more likely to be invasive elsewhere than other grasses. This asymmetry cannot be explained by sampling biases, historical trade links or minimum residence time. Rather it is likely to be due to a combination of: (1) the massive scale of the introduction of South African grasses around the world; (2) specific traits that make South African grasses successful competitors; and (3) the high fire frequency of many South African ecosystems to which many native grasses are adapted, but introduced grasses are not. MAIN CONCLUSION: South Africa has a high diversity of grasses that possess specific traits to cope with fire, grazing and disturbance. This makes them more competitive. Moreover, the high diversity of certain grass lineages in South Africa acts as a reservoir of potential invaders and possibly helps limit invasions in South Africa by promoting fire.
Despite recommendations from numerous health care bodies, some hospitals that care for children have struggled to establish or expand pediatric pharmacy services. The current state of dedicated ...pediatric operational and clinical pharmacy services was characterized by results from a survey of hospitals that provide care to pediatric patients. The discussion of quality of care, safety, and financial impact is meant to provide concepts for justification of pediatric pharmacy service expansion.
The analysis of polyploid genomes is problematic because homeologous subgenome sequences are closely related. This relatedness makes it difficult to assign individual sequences to the specific ...subgenome from which they are derived, and hinders the development of polyploid whole genome assemblies.
We here present a next-generation sequencing (NGS)-based approach for assignment of subgenome-specific base-identity at sites containing homeolog-specific polymorphisms (HSPs): 'HSP base Assignment using NGS data through Diploid Similarity' (HANDS). We show that HANDS correctly predicts subgenome-specific base-identity at >90% of assayed HSPs in the hexaploid bread wheat (Triticum aestivum) transcriptome, thus providing a substantial increase in accuracy versus previous methods for homeolog-specific base assignment.
We conclude that HANDS enables rapid and accurate genome-wide discovery of homeolog-specific base-identity, a capability having multiple applications in polyploid genomics.
Screening for Barrett's oesophagus relies on endoscopy, which is invasive and few who undergo the procedure are found to have the condition. We aimed to use machine learning techniques to develop and ...externally validate a simple risk prediction panel to screen individuals for Barrett's oesophagus.
In this prospective study, machine learning risk prediction in Barrett's oesophagus (MARK-BE), we used data from two case-control studies, BEST2 and BOOST, to compile training and validation datasets. From the BEST2 study, we analysed questionnaires from 1299 patients, of whom 880 (67·7%) had Barrett's oesophagus, including 40 with invasive oesophageal adenocarcinoma, and 419 (32·3%) were controls. We randomly split (6:4) the cohort using a computer algorithm into a training dataset of 776 patients and a testing dataset of 523 patients. We compiled an external validation cohort from the BOOST study, which included 398 patients, comprising 198 patients with Barrett's oesophagus (23 with oesophageal adenocarcinoma) and 200 controls. We identified independently important diagnostic features of Barrett's oesophagus using the machine learning techniques information gain and correlation-based feature selection. We assessed multiple classification tools to create a multivariable risk prediction model. Internal validation of the model using the BEST2 testing dataset was followed by external validation using the BOOST external validation dataset. From these data we created a prediction panel to identify at-risk individuals.
The BEST2 study included 40 diagnostic features. Of these, 19 added information gain but after correlation-based feature selection only eight showed independent diagnostic value including age, sex, cigarette smoking, waist circumference, frequency of stomach pain, duration of heartburn and acidic taste, and taking antireflux medication, of which all were associated with increased risk of Barrett's oesophagus, except frequency of stomach pain, with was inversely associated in a case-control population. Logistic regression offered the highest prediction quality with an area under the receiver-operator curve (AUC) of 0·87 (95% CI 0·84–0·90; sensitivity set at 90%; specificity of 68%). In the testing dataset, AUC was 0·86 (0·83–0·89; sensitivity set at 90%; specificity of 65%). In the external validation dataset, the AUC was 0·81 (0·74–0·84; sensitivity set at 90%; specificity of 58%).
Our diagnostic model offers valid predictions of diagnosis of Barrett's oesophagus in patients with symptomatic gastro-oesophageal reflux disease, assisting in identifying who should go forward to invasive confirmatory testing. Our predictive panel suggests that overweight men who have been taking antireflux medication for a long time might merit particular consideration for further testing. Our risk prediction panel is quick and simple to administer but will need further calibration and validation in a prospective study in primary care.
Charles Wolfson Charitable Trust and Guts UK.
LADY MACBETH Carly Brown
The Art of Being Dangerous,
05/2021
Book Chapter
This fictional story is told from the perspective of Elisabet Ney, a celebrated female sculptor and feminist in the 19th century, who is known for her statues of famous personages in Europe and, ...later, Texas. Two years before her death, she completed her last major work: a statue of Shakespeare’s Lady Macbeth, featured overleaf thanks to the Smithsonian American Art Museum.
When I told everyone I was making a sculpture of her, they were surprised. Probably because she is fictional, and I usually sculpt people who are alive. Men, typically. Famous men. Statesmen, war heroes, prominent doctors. I look at
Ionizing radiation has long been known to induce heritable mutagenic change in DNA sequence. However, the genome-wide effect of radiation is not well understood. Here we report the molecular ...properties and frequency of mutations in phenotypically selected mutant lines isolated following exposure of the genetic model flowering plant Arabidopsis thaliana to fast neutrons (FNs). Previous studies suggested that FNs predominantly induce deletions longer than a kilobase in A. thaliana. However, we found a higher frequency of single base substitution than deletion mutations. While the overall frequency and molecular spectrum of fast-neutron (FN)-induced single base substitutions differed substantially from those of "background" mutations arising spontaneously in laboratory-grown plants, G:C>A:T transitions were favored in both. We found that FN-induced G:C>A:T transitions were concentrated at pyrimidine dinucleotide sites, suggesting that FNs promote the formation of mutational covalent linkages between adjacent pyrimidine residues. In addition, we found that FNs induced more single base than large deletions, and that these single base deletions were possibly caused by replication slippage. Our observations provide an initial picture of the genome-wide molecular profile of mutations induced in A. thaliana by FN irradiation and are particularly informative of the nature and extent of genome-wide mutation in lines selected on the basis of mutant phenotypes from FN-mutagenized A. thaliana populations.
Polycystic ovary syndrome(PCOS) is the most common endocrine disorder in reproductive-aged women. Women with PCOS frequently have metabolic complications including insulin resistance(IR), early ...diabetes, hypertension and dyslipidemia. Recent studies have demonstrated an association between PCOS and another metabolic complication: nonalcoholic fatty liver disease(NAFLD). NAFLD occurs as a result of abnormal lipid handling by the liver, which sensitizes the liver to injury and inflammation. It can progress to nonalcoholic steatohepatitis(NASH), which is characterized by hepatocyte injury and apoptosis. With time and further inflammation, NASH can progress to cirrhosis. Thus, given the young age at which NAFLD may occur in PCOS, these women may be at significant risk for progressive hepatic injury over the course of their lives. Many potential links between PCOS and NAFLD have been proposed, most notably IR and hyperandrogenemia. Further studies are needed to clarify the association between PCOS and NAFLD. In the interim, clinicians should be aware of this connection and consider screening for NAFLD in PCOS patients who have other metabolic risk factors. The optimal method of screening is unknown. However, measuring alanine aminotransferase and/or obtaining ultrasound on high-risk patients can be considered. First line treatment consists of lifestyle interventions and weight loss, with possible pharmacologic interventions in some cases.
Three possible indicators of desiccation-tolerance in ang10sperms: sucrose accumulation and hexose sugar flux, an increase in hexokinase activity, and accumulation of LEA-like proteins, were ...investigated and compared during dehydration between two moncotyledonous poikilochlorophyllous resurrection angiosperm species; Xerophyta schlecterii and Xerophyta humilis, and a dicotyledonous homiochlorophyllous resurrection species, Craterostigma wilmsii. Comparisons were also made with Xerophyta viscosa, using data from Whittaker et al, (2001). Soluble sugar concentrations and hexokinase activities were also examined during rehydration of the three species. Sucrose was accumulated during dehydration in all species examined. However, C. wilmsii had completed sucrose accumulation by the intermediate stages of drying, whereas Xhumilis exhibited a late accumulation. It was not clear if Xschlecterii exhibited late sucrose accumulation due to high standard deviations in the results. C. wilmsii accumulated higher sucrose levels than the two poikilochlorophyllous species. During rehydration the sucrose concentrations dropped in all three species, and was probably being used as an energy source for the resumption of metabolism. Glucose and fructose concentrations were relatively constant during dehydration in all three species, and did not appear to be contributing greatly to sucrose accumulation. This was further confirmed by the low levels of activity of hexokinase found in all three species during dehydration and rehydration, which suggests that the channelling of glucose and fructose into sucrose biosynthesis is not being upregulated during dehydration. C. wilmsii had an increased level of hexokinase late in dehydration, that may have been in preparation for the rapid rehydration experienced by this homiochlorophyllous species, where hexokinase would need to rapidly channel glucose and fructose into metabolism. There was not an increase in activity at the period of highest sucrose accumulation in this species. The activity of hexokinase was relatively constant throughout dehydration and rehydration for Xschlecterii, as it was for Xhumilis. Glucose and fructose levels dropped slightly in C. wilmsii during rehydration but remained relatively constant in the two poikilochlorophyllous species. The presence of LEA-like proteins was found in all three species, although the bands were very faint for X viscosa and Xhumilis. In Xschlecterii the bands were clear in the dehydrated leaf sample, but were faint or absent in the hydrated sample. It is possible that the proteins in this species were upregulated or induced by drying. A protein common to all three species in dehydrated and hydrated samples was observed between the 22.5 kDa and the 15.3 kDa molecular markers.
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