Two key events associated with a transposable element burst occurred during rice domestication

Transposable elements shape genome evolution through periodic bursts of amplification. In this study we exploited knowledge of the components of the mPing/Ping/Pong TE family in four rice strains undergoing mPing bursts to track their copy numbers and distribution in a large collection of genomes from the wild progenitor Oryza rufipogon and domesticated Oryza sativa (rice). We characterized two events that occurred to the autonomous Ping element and appear to be critical for mPing hyperactivity. First, a point mutation near the end of the element created a Ping variant ( Ping16A ) with reduced transposition. The proportion of strains with Ping16A has increased during domestication while the original Ping (Ping16G) has been dramatically reduced. Second, transposition of Ping16A into a Stowaway element generated a locus ( Ping16A_Stow ) whose presence correlates with strains that have high mPing copies. Finally, demonstration that Pong elements have been stably silenced in all strains analyzed indicates that sustained activity of the mPing/Ping family during domestication produced the components necessary for the mPing burst, not the loss of epigenetic regulation

Detecting Heart Disease from Multi-View Ultrasound Images via Supervised Attention Multiple Instance Learning

Aortic stenosis (AS) is a degenerative valve condition that causes substantial morbidity and mortality. This condition is under-diagnosed and under-treated. In clinical practice, AS is diagnosed with expert review of transthoracic echocardiography, which produces dozens of ultrasound images of the heart. Only some of these views show the aortic valve. To automate screening for AS, deep networks must learn to mimic a human expert's ability to identify views of the aortic valve then aggregate across these relevant images to produce a study-level diagnosis. We find previous approaches to AS detection yield insufficient accuracy due to relying on inflexible averages across images. We further find that off-the-shelf attention-based multiple instance learning (MIL) performs poorly. We contribute a new end-to-end MIL approach with two key methodological innovations. First, a supervised attention technique guides the learned attention mechanism to favor relevant views. Second, a novel self-supervised pretraining strategy applies contrastive learning on the representation of the whole study instead of individual images as commonly done in prior literature. Experiments on an open-access dataset and an external validation set show that our approach yields higher accuracy while reducing model size.Comment: multiple-instance learning; self-supervised learning; semi-supervised learning; medical imagin

Short-Term Effects of Ketamine and Isoflurane on Left Ventricular Ejection Fraction in an Experimental Swine Model

Background. General anesthesia is an essential element of experimental medical procedures. Ketamine and isoflurane are agents commonly used to induce and maintain anesthesia in animals. The cardiovascular effects of these anesthetic agents are diverse, and the response of global myocardial function is unknown. Methods. In a series of 15 swine, echocardiography measurements of left ventricular ejection fraction (LVEF) were obtained before the animals received anesthesia (baseline), after an intramuscular injection of ketamine (postketamine) and after inhaled isoflurane (postisoflurane). Results. The mean LVEF of an unanesthetized swine was 47 ± 3%. There was a significant decrease in the mean LVEF after administration of ketamine to 41 + 6.5% (P = 0.003). The addition of inhaled isoflurane did not result in further decrease in mean LVEF (mean LVEF 38 ± 7.2%, P = 0.22). Eight of the swine had an increase in their LVEF with sympathetic stimulation. Conclusions. In our experimental model the administration of ketamine was associated with decreased LV function. The decrease may be largely secondary to a blunting of sympathetic tone. The addition of isoflurane to ketamine did not significantly change LV function. A significant number of animals had returned to preanesthesia LV function with sympathetic stimulation

Transesophageal echocardiography in cryptogenic stroke and patent foramen ovale: analysis of putative high-risk features from the risk of paradoxical embolism database

BACKGROUND Patent foramen ovale (PFO) is associated with cryptogenic stroke (CS), although the pathogenicity of a discovered PFO in the setting of CS is typically unclear. Transesophageal echocardiography features such as PFO size, associated hypermobile septum, and presence of a right-to-left shunt at rest have all been proposed as markers of risk. The association of these transesophageal echocardiography features with other markers of pathogenicity has not been examined. METHODS AND RESULTS We used a recently derived score based on clinical and neuroimaging features to stratify patients with PFO and CS by the probability that their stroke is PFO-attributable. We examined whether high-risk transesophageal echocardiography features are seen more frequently in patients more likely to have had a PFO-attributable stroke (n=637) compared with those less likely to have a PFO-attributable stroke (n=657). Large physiologic shunt size was not more frequently seen among those with probable PFO-attributable strokes (odds ratio [OR], 0.92; P=0.53). The presence of neither a hypermobile septum nor a right-to-left shunt at rest was detected more often in those with a probable PFO-attributable stroke (OR, 0.80; P=0.45; OR, 1.15; P=0.11, respectively). CONCLUSIONS We found no evidence that the proposed transesophageal echocardiography risk markers of large PFO size, hypermobile septum, and presence of right-to-left shunt at rest are associated with clinical features suggesting that a CS is PFO-attributable. Additional tools to describe PFOs may be useful in helping to determine whether an observed PFO is incidental or pathogenically related to CS

Inhibitors of Helicobacter pylori Protease HtrA Found by ‘Virtual Ligand’ Screening Combat Bacterial Invasion of Epithelia

Background: The human pathogen Helicobacter pylori (H. pylori) is a main cause for gastric inflammation and cancer. Increasing bacterial resistance against antibiotics demands for innovative strategies for therapeutic intervention. Methodology/Principal Findings: We present a method for structure-based virtual screening that is based on the comprehensive prediction of ligand binding sites on a protein model and automated construction of a ligand-receptor interaction map. Pharmacophoric features of the map are clustered and transformed in a correlation vector (‘virtual ligand’) for rapid virtual screening of compound databases. This computer-based technique was validated for 18 different targets of pharmaceutical interest in a retrospective screening experiment. Prospective screening for inhibitory agents was performed for the protease HtrA from the human pathogen H. pylori using a homology model of the target protein. Among 22 tested compounds six block E-cadherin cleavage by HtrA in vitro and result in reduced scattering and wound healing of gastric epithelial cells, thereby preventing bacterial infiltration of the epithelium. Conclusions/Significance: This study demonstrates that receptor-based virtual screening with a permissive (‘fuzzy’) pharmacophore model can help identify small bioactive agents for combating bacterial infection

Blood pressure changes during routine transthoracic echocardiography

Background: Increased afterload affects many of the flow dependent metrics assessed during transthoracic echocardiography (TTE) especially in the evaluation valvular disease. A single timepoint blood pressure (BP) may not accurately reflect the afterload present at the time of flow-dependent imaging and quantification. We assessed the magnitude of change in BP at discrete timepoints during routine TTE. Method: We conducted a prospective study where participants underwent automated BP measurement while undergoing a clinically indicated TTE. The first reading was obtained right after the patient lay supine and subsequent readings were taken at 10-min intervals during image acquisition. Result: We included 50 participants (66% were male, with a mean age of 64 years). After 10 min, 40 (80%) participants had a drop in systolic BP of >10 mmHg. Compared to the baseline, there was a significant drop in systolic BP (mean decrease 20.0 ± 12.8 mmHg; P < 0.05), and diastolic BP (mean decrease 15.7 ± 13.2 mmHg; P < 0.05) at 10 min. The systolic BP remained different from the baseline value throughout the duration of the study (average decrease from baseline to study end was 12.4 ± 16.0 mmHg, p < 0.05). Conclusion: BP recorded just prior to TTE does not accurately reflect the afterload present during most of the study. This finding has important implications for valvular heart disease imaging protocols that incorporate flow dependent metrics, where the presence or absence of hypertension may lead to under- or over-estimation of disease severity

Two key events associated with a transposable element burst occurred during rice domestication

Transposable elements shape genome evolution through periodic bursts of amplification. In this study we exploited knowledge of the components of the mPing/Ping/Pong TE family in four rice strains undergoing mPing bursts to track their copy numbers and distribution in a large collection of genomes from the wild progenitor Oryza rufipogon and domesticated Oryza sativa (rice). We characterized two events that occurred to the autonomous Ping element and appear to be critical for mPing hyperactivity. First, a point mutation near the end of the element created a Ping variant ( Ping16A ) with reduced transposition. The proportion of strains with Ping16A has increased during domestication while the original Ping (Ping16G) has been dramatically reduced. Second, transposition of Ping16A into a Stowaway element generated a locus ( Ping16A_Stow ) whose presence correlates with strains that have high mPing copies. Finally, demonstration that Pong elements have been stably silenced in all strains analyzed indicates that sustained activity of the mPing/Ping family during domestication produced the components necessary for the mPing burst, not the loss of epigenetic regulation