Miracle-dz/UniFAR-FTUs huggingface dataset:
Bacillus anthracis Virulence Regulator AtxA Binds Specifically to the pagA Promoter Region

Anthrax toxin activator (AtxA) regulates the major virulence genes in Bacillus anthracis. The bacterium produces the anthrax toxins, and understanding the mechanism of toxin production may facilitate the development of therapeutics for B. anthracis infection. Since the discovery of AtxA 25 years ago, the mechanism by which it regulates its targets has largely remained a mystery. Here, we provide evidence that AtxA binds to the promoter region of the pagA gene encoding the main central protective antigen (PA) component of the anthrax toxin. These data suggest that AtxA binding plays a direct role in gene regulation. Our work also assists in clarifying the role of CO2 in AtxA’s gene regulation and provides more evidence for the role of AtxA phosphorylation in virulence gene regulation. ABSTRACT Anthrax toxin activator (AtxA) is the master virulence gene regulator of Bacillus anthracis. It regulates genes on the chromosome as well as the pXO1 and pXO2 plasmids. It is not clear how AtxA regulates these genes, and direct binding of AtxA to its targets has not been shown. It has been previously suggested that AtxA and other proteins in the Mga/AtxA global transcriptional regulators family bind to the curvature of their DNA targets, although this has never been experimentally proven. Using electrophoretic mobility shift assays, we demonstrate that AtxA binds directly to the promoter region of pagA upstream of the RNA polymerase binding site. We also demonstrate that in vitro, CO2 appears to have no role in AtxA binding. However, phosphomimetic and phosphoablative substitutions in the phosphotransferase system (PTS) regulation domains (PRDs) do appear to influence AtxA binding and pagA regulation. In silico, in vitro, and in vivo analyses demonstrate that one of two hypothesized stem-loops located upstream of the RNA polymerase binding site in the pagA promoter region is important for AtxA binding in vitro and pagA regulation in vivo. Our study clarifies the mechanism by which AtxA interacts with one of its targets. IMPORTANCE Anthrax toxin activator (AtxA) regulates the major virulence genes in Bacillus anthracis. The bacterium produces the anthrax toxins, and understanding the mechanism of toxin production may facilitate the development of therapeutics for B. anthracis infection. Since the discovery of AtxA 25 years ago, the mechanism by which it regulates its targets has largely remained a mystery. Here, we provide evidence that AtxA binds to the promoter region of the pagA gene encoding the main central protective antigen (PA) component of the anthrax toxin. These data suggest that AtxA binding plays a direct role in gene regulation. Our work also assists in clarifying the role of CO2 in AtxA’s gene regulation and provides more evidence for the role of AtxA phosphorylation in virulence gene regulation.
Dynamics of wrinkling in ultrathin elastic sheets

Significance Elastic instabilities provide a means of generating regular topographies with a well-defined wavelength. For example, a thin elastic film attached to a softer substrate buckles into an array of regular wrinkles under quasistatic compression. The wrinkle wavelength is selected by the mechanical properties of the system so that different wavelengths are typically attained through variation of the film thickness. Here, we show that, for a film of given thickness, variation in the wrinkle wavelength can be achieved dynamically. Our study of impact-induced wrinkling demonstrates that the inertial response of the substrate results in an evolving wrinkle wavelength, opening the route toward dynamic tuning of wrinkle-patterned topographies. The wrinkling of thin elastic objects provides a means of generating regular patterning at small scales in applications ranging from photovoltaics to microfluidic devices. Static wrinkle patterns are known to be governed by an energetic balance between the object’s bending stiffness and an effective substrate stiffness, which may originate from a true substrate stiffness or from tension and curvature along the wrinkles. Here, we investigate dynamic wrinkling induced by the impact of a solid sphere onto an ultrathin polymer sheet floating on water. The vertical deflection of the sheet’s center induced by impact draws material radially inward, resulting in an azimuthal compression that is relieved by the wrinkling of the entire sheet. We show that this wrinkling is truly dynamic, exhibiting features that are qualitatively different to those seen in quasistatic wrinkling experiments. Moreover, we show that the wrinkles coarsen dynamically because of the inhibiting effect of the fluid inertia. This dynamic coarsening can be understood heuristically as the result of a dynamic stiffness, which dominates the static stiffnesses reported thus far, and allows control of wrinkle wavelength.
Opportunities in Interventional and Diagnostic Imaging by Using High-performance Low-Field-Strength MRI.

Background Commercial low-field-strength MRI systems are generally not equipped with state-of-the-art MRI hardware, and are not suitable for demanding imaging techniques. An MRI system was developed that combines low field strength (0.55 T) with high-performance imaging technology. Purpose To evaluate applications of a high-performance low-field-strength MRI system, specifically MRI-guided cardiovascular catheterizations with metallic devices, diagnostic imaging in high-susceptibility regions, and efficient image acquisition strategies. Materials and Methods A commercial 1.5-T MRI system was modified to operate at 0.55 T while maintaining high-performance hardware, shielded gradients (45 mT/m; 200 T/m/sec), and advanced imaging methods. MRI was performed between January 2018 and April 2019. T1, T2, and T2* were measured at 0.55 T; relaxivity of exogenous contrast agents was measured; and clinical applications advantageous at low field were evaluated. Results There were 83 0.55-T MRI examinations performed in study participants (45 women; mean age, 34 years ± 13). On average, T1 was 32% shorter, T2 was 26% longer, and T2* was 40% longer at 0.55 T compared with 1.5 T. Nine metallic interventional devices were found to be intrinsically safe at 0.55 T (<1°C heating) and MRI-guided right heart catheterization was performed in seven study participants with commercial metallic guidewires. Compared with 1.5 T, reduced image distortion was shown in lungs, upper airway, cranial sinuses, and intestines because of improved field homogeneity. Oxygen inhalation generated lung signal enhancement of 19% ± 11 (standard deviation) at 0.55 T compared with 7.6% ± 6.3 at 1.5 T (P = .02; five participants) because of the increased T1 relaxivity of oxygen (4.7e-4 mmHg-1sec-1). Efficient spiral image acquisitions were amenable to low field strength and generated increased signal-to-noise ratio compared with Cartesian acquisitions (P < .02). Representative imaging of the brain, spine, abdomen, and heart generated good image quality with this system. Conclusion This initial study suggests that high-performance low-field-strength MRI offers advantages for MRI-guided catheterizations with metal devices, MRI in high-susceptibility regions, and efficient imaging. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Grist in this issue.
Derepression of the smvA Efflux System Arises in Clinical Isolates of Proteus mirabilis and Reduces Susceptibility to Chlorhexidine and Other Biocides

Proteus mirabilis is a common pathogen of the catheterized urinary tract and often described as intrinsically resistant to the biocide chlorhexidine (CHD). Here, we demonstrate that derepression of the smvA efflux system has occurred in clinical isolates of P. mirabilis and reduces susceptibility to CHD and other cationic biocides. ABSTRACT Proteus mirabilis is a common pathogen of the catheterized urinary tract and often described as intrinsically resistant to the biocide chlorhexidine (CHD). Here, we demonstrate that derepression of the smvA efflux system has occurred in clinical isolates of P. mirabilis and reduces susceptibility to CHD and other cationic biocides. Compared with other isolates examined, P. mirabilis RS47 exhibited a significantly higher CHD MIC (≥512 μg/ml) and significantly greater expression of smvA. Comparison of the RS47 smvA and cognate smvR repressor with sequences from other isolates indicated that RS47 carries an inactivated smvR. Complementation of RS47 with a functional smvR from isolate RS50a (which exhibited the lowest smvA expression and lowest CHD MIC) reduced smvA expression by ∼59-fold and markedly lowered the MIC of CHD and other cationic biocides. Although complementation of RS47 did not reduce MICs to concentrations observed in isolate RS50a, the significantly lower polymyxin B MIC of RS50a indicated that differences in lipopolysaccharide (LPS) structure are also a factor in P. mirabilis CHD susceptibility. To determine if exposure to CHD can select for mutations in smvR, clinical isolates with the lowest CHD MICs were adapted to grow at increasing concentrations of CHD up to 512 μg/ml. Analysis of the smvR in adapted populations indicated that mutations predicted to inactivate smvR occurred following CHD exposure in some isolates. Collectively, our data show that smvA derepression contributes to reduced biocide susceptibility in P. mirabilis, but differences in LPS structure between strains are also likely to be an important factor.
Novel Genetic Markers for Early Detection of Elevated Breast Cancer Risk in Women

This study suggests that two newly discovered variants in the MSH2 gene, which codes for a DNA mismatch repair (MMR) protein, can be associated with a high risk of breast cancer. While variants in the MSH2 gene are known to be linked with an elevated cancer risk, the MSH2 gene is not a part of the standard kit for testing patients for elevated breast cancer risk. Here we used the results of genetic testing of women diagnosed with breast cancer, but who did not have variants in BRCA1 and BRCA2 genes. Instead, the test identified four variants with unknown significance (VUS) in the MSH2 gene. Here, we carried in silico analysis to develop a classifier that can distinguish pathogenic from benign mutations in MSH2 genes taken from ClinVar. The classifier was then used to classify VUS in MSH2 genes, and two of them, p.Ala272Val and p.Met592Val, were predicted to be pathogenic mutations. These two mutations were found in women with breast cancer who did not have mutations in BRCA1 and BRCA2 genes, and thus they are suggested to be considered as new bio-markers for the early detection of elevated breast cancer risk. However, before this is done, an in vitro validation of mutation pathogenicity is needed and, moreover, the presence of these mutations should be demonstrated in a higher number of patients or in families with breast cancer history.
Extracellular miRNAs as Biomarkers of Head and Neck Cancer Progression and Metastasis

Head and neck squamous cell carcinomas (HNSCCs) contribute to over 300,000 deaths every year worldwide. Although the survival rates have improved in some groups of patients, mostly due to new treatment options and the increasing percentage of human papillomavirus (HPV)-related cancers, local recurrences and second primary tumors remain a great challenge for the clinicians. Presently, there is no biomarker for patient surveillance that could help identify patients with HNSCC that are more likely to experience a relapse or early progression, potentially requiring closer follow-up or salvage treatment. MicoRNAs (miRNAs) are non-coding RNA molecules that posttranscriptionally modulate gene expression. They are highly stable and their level can be measured in biofluids including serum, plasma, and saliva, enabling quick results and allowing for repeated analysis during and after the completion of therapy. This has cemented the role of miRNAs as biomarkers with a huge potential in oncology. Since altered miRNA expression was described in HNSCC and many miRNAs play a role in radio- and chemotherapy resistance, cancer progression, and metastasis, they can be utilized as biomarkers of these phenomena. This review outlines recent discoveries in the field of extracellular miRNA-based biomarkers of HNSCC progression and metastasis, with a special focus on HPV-related cancers and radioresistance.
Association of Epicardial Adipose Tissue Thickness with Extent and Complexity of Coronary Artery Disease in Patients with Acute Coronary Syndrome.

Background Epicardial adipose tissue (EAT) secretes proatherogenic and proinflammatory cytokines and affects cardiac morphology and functions. The aim of this study was to measure EAT thickness in patients without previous coronary artery disease (CAD) who were admitted with acute coronary syndrome (ACS), and determine its relationship to ACS clinical risk scores, and the severity and complexity of CAD. Methods This study enrolled 150 patients (mean age 59.7 ± 11.1 years, 83% men), including 75 with non-ST elevated myocardial infarction (NSTEMI group) and 75 with ST elevated myocardial infarction (STEMI group). Cardiovascular risk factors and laboratory analyses were recorded. The Global Registry of Acute Coronary Events (GRACE) risk score, TIMI clinical, SYNTAX and Gensini angiographic scores were calculated according to guidelines. EAT thickness was measured by echocardiography above the free wall of the right ventricle, perpendicular to the aortic annulus. Results There were no significant differences in CAD risk factors, clinical, demographic features, anthropometric measurements, or EAT thickness (mean 5.94 ± 1.17 mm) between the two groups. In the patients with ACS, there were no direct correlations between EAT thickness and TIMI, GRACE, SYNTAX and Gensini scores. There were positive and significant correlations between the thickness of EAT and SYNTAX (r = 0.243, p = 0.035) and Gensini (r = 0.394, p < 0.001) scores only in the NSTEMI group. Multivariate linear regression analysis showed that EAT predicted SYNTAX (β = 0.06, p < 0.001) and Gensini (β = 0.04, p = 0.006) scores, but not TIMI score (β = 0.1, p = 0.06) in the patients overall. Conclusions EAT thickness measured by 2D echocardiography was not correlated with the extent or complexity of CAD in the ACS patients. However, after adjusting for confounding factors, multivariate linear regression analysis showed that EAT predicted SYNTAX and Gensini scores in these patients.
Surgical Explantation of Bone-Anchored Hearing Devices: A 10-year Single Institution Review

Objective To identify clinical variables associated with the decision to surgically discontinue bone-anchored hearing device function. Study Design Retrospective chart review. Setting Tertiary neurotology referral center. Subjects and Methods This study examines surgical interventions performed on existing bone-anchored hearing devices at a single institution from 2008 to 2018. Patient characteristics, indications for implantation, and complications prompting surgical intervention were assessed. Results Seventy-seven cases were included in this study. Among patients in the younger cohort (<37 years old), 100% (13 of 13) of those discontinuing their device had a contralateral normal-hearing ear. Conversely, 0% (0 of 14) of the younger patients with bilateral hearing loss surgically discontinued their devices. Within the older cohort (≥37 years old), female patients (P = .002) and those with an increased body mass index (P = .035) were more likely to surgically discontinue their devices. Multivariate analysis revealed that a contralateral normal-hearing ear (P = .001) and infection without soft tissue overgrowth of the abutment (P = .026) were the strongest predictors of device discontinuation, after adjusting for potential confounders. Conclusion Surgical discontinuation is associated with several clinical variables. Targeted interventions that are viable alternatives to removal, such as device relocation, should be presented to younger patients with a contralateral normal-hearing ear who experience persistent complications. Patients with persistent infection in the absence of soft tissue overgrowth would especially benefit from enhanced counseling on proper hygiene.
Potential of on‐scalp MEG: Robust detection of human visual gamma‐band responses

Electrophysiological signals recorded intracranially show rich frequency content spanning from near‐DC to hundreds of hertz. Noninvasive electromagnetic signals measured with electroencephalography (EEG) or magnetoencephalography (MEG) typically contain less signal power in high frequencies than invasive recordings. Particularly, noninvasive detection of gamma‐band activity (>30 Hz) is challenging since coherently active source areas are small at such frequencies and the available imaging methods have limited spatial resolution. Compared to EEG and conventional SQUID‐based MEG, on‐scalp MEG should provide substantially improved spatial resolution, making it an attractive method for detecting gamma‐band activity. Using an on‐scalp array comprised of eight optically pumped magnetometers (OPMs) and a conventional whole‐head SQUID array, we measured responses to a dynamic visual stimulus known to elicit strong gamma‐band responses. OPMs had substantially higher signal power than SQUIDs, and had a slightly larger relative gamma‐power increase over the baseline. With only eight OPMs, we could obtain gamma‐activity source estimates comparable to those of SQUIDs at the group level. Our results show the feasibility of OPMs to measure gamma‐band activity. To further facilitate the noninvasive detection of gamma‐band activity, the on‐scalp OPM arrays should be optimized with respect to sensor noise, the number of sensors and intersensor spacing.
When facilitation meets clonal integration in forest canopies.

Few studies have explored how - within the same system - clonality and positive plant-plant interactions might interact to regulate plant community composition. Canopy-dwelling epiphytes in species-rich forests provide an ideal system for studying this because many epiphytic vascular plants undertake clonal growth and because vascular epiphytes colonize canopy habitats after the formation of non-vascular epiphyte (i.e. bryophyte and lichen) mats. We investigated how clonal integration of seven dominant vascular epiphytes influenced inter-specific interactions between vascular epiphytes and non-vascular epiphyte mats in a subtropical montane moist forest in Southwest China. Both clonal integration and environmental buffering from non-vascular epiphytes increased survival and growth of vascular epiphytes. The benefits of clonal integration for vascular epiphytes were higher when non-vascular epiphytes were removed. Similarly, facilitation from non-vascular epiphytes played a more important role when clonal integration of vascular epiphytes was eliminated. Overall, clonal integration had greater benefits than inter-specific facilitation. This study provides novel evidence for interactive effects of clonality and facilitation between vascular and non-vascular species, and has implications for our understanding of a wide range of ecosystems where both high levels of clonality and facilitation are expected to occur.
Non-compaction cardiomyopathy in pregnancy: a case report of spongy myocardium in both mother and foetus and systematic review of literature

Abstract Purpose Cardiovascular disease is the main nonobstetric cause of maternal death during pregnancy and is present in 0.5–4% of pregnancies in the western world. While hypertensive disorders remain the most frequent events, occurring in 6–8% of all pregnancies, cardiomyopathies are rare but encompass high complication rates. The aim of this systematic review is to report all data available up to date regarding pregnancies in patients with left ventricular noncompaction (LVNC) cardiomyopathy. Methods PubMed, Medline, Cochrane, Scopus and Embase were searched, up to January 2019, using combinations of these terms: left ventricular noncompaction, hypertrabeculation cardiomyopathy, spongy myocardium, spongiform cardiomyopathy and delivery, gestation, pregnancy, cesarean section (CS). After careful selection, 22 articles, reporting a total of 30 cases, including our own were included in the review. Results Fifteen out of 26 women (58%) were diagnosed with LVNC before pregnancy. Around 56% of women presented with symptoms during pregnancy while 44% were asymptomatic. Heart failure is by far the most common symptom occurring in almost half the cases. Uncommon clinical presentations included a heart attack, a stroke, and pulmonary hypertension. Timing of delivery was reported preterm in 58% of cases and at term in 42%. Eleven women gave birth through vaginal delivery, while 15 (58%) underwent a CS. Our reported case is the first case of a pregnancy where both mother and fetus are affected by LVNC and the fetus is diagnosed prenatally. Conclusions LVNC is not a contraindication for pregnancy, but clearly increases the risk of preterm birth and the rate of cesarean section. On the other hand, pregnancy in a LVNC patient exposes her to increased risk of clinical deterioration. Further studies are needed to better characterize the management of pregnancies in women with cardiomyopathies.
An Efficient Destination Prediction Approach Based on Future Trajectory Prediction and Transition Matrix Optimization

Destination prediction is an essential task in various mobile applications and up to now many methods have been proposed. However, existing methods usually suffer from the problems of heavy computational burden, data sparsity, and low coverage. Therefore, a novel approach named DestPD is proposed to tackle the aforementioned problems. Differing from an earlier approach that only considers the starting and current location of a partial trip, DestPD first determines the most likely future location and then predicts the destination. It comprises two phases, the offline training and the online prediction. During the offline training, transition probabilities between two locations are obtained via Markov transition matrix multiplication. In order to improve the efficiency of matrix multiplication, we propose two data constructs, Efficient Transition Probability (ETP) and Transition Probabilities with Detours (TPD). They are capable of pinpointing the minimum amount of needed computation. During the online prediction, we design Obligatory Update Point (OUP) and Transition Affected Area (TAA) to accelerate the frequent update of ETP and TPD for recomputing the transition probabilities. Moreover, a new future trajectory prediction approach is devised. It captures the most recent movement based on a query trajectory. It consists of two components: similarity finding through Best Path Notation (BPN) and best node selection. Our novel BPN similarity finding scheme keeps track of the nodes that induces inefficiency and then finds similarity fast based on these nodes. It is particularly suitable for trajectories with overlapping segments. Finally, the destination is predicted by combining transition probabilities and the most probable future location through Bayesian reasoning. The DestPD method is proved to achieve one order of cut in both time and space complexity. Furthermore, the experimental results on real-world and synthetic datasets have shown that DestPD consistently surpasses the state-of-the-art methods in terms of both efficiency (approximately over 100 times faster) and accuracy.