Cyclic Signaling Research Articles

Fault Stage Feature Extraction Method Based on Antinoise Gradient Operator Morphological Filters

The cyclical impact signal aroused by mechanical fault contains feature information, such as fault type and fault stage. However, a transient impact component is usually modulated on the fundamental frequency and mixed with a large amount of noise. Thus, it is difficult to be extracted effectively. A feature extraction method of faults stage is presented based on morphological filter theory. An antinoise morphological gradient operator is applied to signal filtering. This operator can weaken the noise and clearly highlight the impact characteristics of different fault stages. The kurtosis of the spectrum band, including the passing frequencies of mechanical components, is used to differentiate fault stages. The applications on simulation signals and bearing test data indicate that this method can realize accurate extraction of fault characteristic frequency submerged in noise and effective distinction of different fault stages.

Identification of ligand-specific G protein-coupled receptor states and prediction of downstream efficacy via data-driven modeling.

Ligand binding stabilizes different G protein-coupled receptor states via a complex allosteric process that is not completely understood. Here, we have derived free energy landscapes describing activation of the β2 adrenergic receptor bound to ligands with different efficacy profiles using enhanced sampling molecular dynamics simulations. These reveal shifts toward active-like states at the Gprotein-binding site for receptors bound to partial and full agonists, and that the ligands modulate the conformational ensemble of the receptor by tuning protein microswitches. We indeed find an excellent correlation between the conformation of the microswitches close to the ligand binding site and in the transmembrane region and experimentally reported cyclic adenosine monophosphate signaling responses. Dimensionality reduction further reveals the similarity between the unique conformational states induced by different ligands, and examining the output of classifiers highlights two distant hotspots governing agonism on transmembrane helices 5 and 7.

Effect of fuel injection parameters on performance characteristics and emissions of a thermoacoustic system

The present study experimentally investigates the effects of different fuel injection parameters on performance characteristics and emissions of a thermoacoustic pulse combustor. Several fuel nozzles were designed to enable various injection schemes. Pressure, photoelectric and radical spectra signals were measured for different fuel nozzles under the same fuel supply pressure; evaluation indexes, to describe the running performance of the pulse combustor, were introduced based on the pressure signal. Preliminary analysis of the pressure signals and evaluation indexes showed that the fuel nozzle with a small top angle was beneficial to the operation performance of the pulse combustor, and there exist an optimal spacing of nozzle holes to enhance the combustor performance most effectively. To further study the influence mechanism, a detailed analysis of the cyclic behaviors of pressure and photoelectric signals was then conducted. Several crests were observed in the cyclic photoelectric signal, all showed different characteristics for different fuel nozzle parameters. It was found that these crests influenced heat release distribution, and therefore, the thermoacoustic behavior and operation performance of the pulse combustor. Rayleigh's efficiency was calculated to quantitatively analyze the effect of various crests on the thermoacoustic coupling in the combustor. In addition to operation performance, radical emissions for different fuel nozzle parameters were also investigated. The obtained radical signals have five spectra peaks (309.35 nm, 430.48 nm, 516.19 nm, 766.19 nm and 927.12 nm) for liquefied petroleum gas. The larger spectra peaks of the free radicals generally indicated higher combustion chemical reaction intensity. Results showed that the fuel nozzle with the small top angle has large spectra peak values and an optimal spacing of nozzle holes that maximized the combustion intensity. This study benefits the optimal design of the nozzle and the improvement of performance as well as efficiency of the combustor.

Optimal Capacity Allocation for Heavy-Traffic Fixed-Cycle Traffic-Light Queues and Intersections

Setting traffic light signals is a classical topic in traffic engineering, and important in heavy-traffic conditions when green times become scarce and longer queues are inevitably formed. For the fixed-cycle traffic-light queue, an elementary queueing model for one traffic light with cyclic signaling, we obtain heavy-traffic limits that capture the long-term queue behavior. We leverage the limit theorems to obtain sharp performance approximations for one queue in heavy traffic. We also consider optimization problems that aim for optimal division of green times among multiple conflicting traffic streams. We show that inserting heavy-traffic approximations leads to tractable optimization problems and close-to-optimal signal prescriptions.

Cyclical Signals from the Labor Market

We consider which labor market variables are the most informative for estimating and now-casting the U.S. output gap using a multivariate trend-cycle decomposition. Although the unemployment rate clearly contains important cyclical information, it also appears to reflect more persistent movements related to labor force participation that could distort inferences about the output gap. Instead, we show that the alternative U-2 unemployment rate (job losers as a percentage of the labor force) provides a more purely cyclical indicator of labor market conditions. To a lesser extent, but consistent with a link of the output gap to real labor costs in a New Keynesian setting, we also find that average hourly earnings are informative about the output gap.

Characteristics of neural growth and cryopreservation of the dorsal root ganglion using three-dimensional collagen hydrogel culture versus conventional culture.

In vertebrates, most somatosensory pathways begin with the activation of dorsal root ganglion (DRG) neurons. The development of an appropriate DRG culture method is a prerequisite for establishing in vitro peripheral nerve disease models and for screening therapeutic drugs. In this study, we compared the changes in morphology, molecular biology, and transcriptomics of chicken embryo DRG cultured on tissue culture plates (T-DRG) versus three-dimensional collagen hydrogels (C-DRG). Our results showed that after 7 days of culture, the transcriptomics of T-DRG and C-DRG were quite different. The upregulated genes in C-DRG were mainly related to neurogenesis, axon guidance, and synaptic plasticity, whereas the downregulated genes in C-DRG were mainly related to cell proliferation and cell division. In addition, the genes related to cycles/pathways such as the synaptic vesicle cycle, cyclic adenosine monophosphate signaling pathway, and calcium signaling pathway were activated, while those related to cell-cycle pathways were downregulated. Furthermore, neurogenesis- and myelination-related genes were highly expressed in C-DRG, while epithelial-mesenchymal transition-, apoptosis-, and cell division-related genes were suppressed. Morphological results indicated that the numbers of branches, junctions, and end-point voxels per C-DRG were significantly greater than those per T-DRG. Furthermore, cells were scattered in T-DRG and more concentrated in C-DRG, with a higher ratio of 5-ethynyl-2'-deoxyuridine (EdU)-positive cells in T-DRG compared with C-DRG. C-DRG also had higher S100 calcium-binding protein B (S100B) and lower α-smooth muscle actin (α-SMA) expression than T-DRG, and contained fewer terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells after 48 hours of serum starvation. After cryopreservation, C-DRG maintained more intact morphological characteristics, and had higher viability and less TUNEL-positive cells than T-DRG. Furthermore, newly formed nerve bundles were able to grow along the existing Schwann cells in C-DRG. These results suggest that C-DRG may be a promising in vitro culture model, with better nerve growth and anti-apoptotic ability, quiescent Schwann cells, and higher viability. Results from this study provide a reference for the construction, storage, and transportation of tissue-engineered nerves. The study was approved by the Ethics Committee of Aier School of Ophthalmology, Central South University, China (approval No. 2020-IRB16), on March 15, 2020.

Concept of design, requirements and generalized architectures of components of the integrated onto-oriented information environment of simulation and processing of cyclic signals

The article gives the reasoning to the relevance of developing a generalized architecture of integrated onto-oriented information environment for simulation and processing of cyclic signals based on the theory of cyclic functional relations, as well as formulates the general requirements to it and its developingt. The research deals with statement of and creating the generalized architectures of the components of the integrated onto-oriented information environment for simulation and processing of cyclic signals, namely, for information-oriented reference system in the field of simulation and processing of cyclic signals; knowledge base of the integrated information environment, the core of which is the corresponding ontology; onto-oriented expert decision support system in the field of simulation and processing of cyclic signals; information system with onto-oriented architecture for simulation and processing of cyclic signals.

Fault Identification in Hydraulic Rock Drills from Indirect Measurement During Operation

This work presents a method for on-line condition monitoring of a hydraulic rock drill, though some of the findings can likely be applied in other applications. A fundamental difficulty for the rock drill application is discussed, namely the similarity between frequencies of internal standing waves and rock drill operation. This results in unpredictable pressure oscillations and superposition, which makes synchronization between measurement and model difficult. To overcome this, a data driven approach is proposed. The number and types of sensors are restricted due to harsh environmental conditions, and only operational data is available. Some faults are shown to be detectable using hand-crafted engineering features, with a direct physical connection to the fault of interest. Such features are easily interpreted and are shown to be robust against disturbances. Other faults are detected by classifying measured signals against a known reference. Dynamic Time Warping is shown to be an efficient way to measure similarity for cyclic signals with stochastic elements from disturbances, wave propagation and different durations, and also for cases with very small differences in measured pressure signals. Together, the two methods enables a step towards condition monitoring of a rock drill, robustly detecting very small changes in behaviour using a minimum amount of sensors.

CryoEM map of Pseudomonas aeruginosa PilQ enables structural characterization of TsaP

The type IV pilus machinery is a multi-protein complex that polymerizes and depolymerizes a pilus fiber used for attachment, twitching motility, phage adsorption, natural competence, protein secretion, and surface-sensing. An outer membrane secretin pore is required for passage of the pilus fiber out of the cell. Herein, the structure of the tetradecameric secretin, PilQ, from the Pseudomonas aeruginosa type IVa pilus system was determined to 4.3Å and 4.4Å resolution in the presence and absence of C7 symmetric spikes, respectively. The heptameric spikes were found to be two tandem C-terminal domains of TsaP. TsaP forms a belt around PilQ and while it is not essential for twitching motility, overexpression of TsaP triggers a signal cascade upstream of PilY1 leading to cyclic di-GMP up-regulation. These results resolve the identity of the spikes identified with Proteobacterial PilQ homologs and may reveal a new component of the surface-sensing cyclic di-GMP signal cascade.

A Luminescence-Based Coupled Enzyme Assay Enables High-Throughput Quantification of the Bacterial Second Messenger 3'3'-Cyclic-Di-AMP.

Cyclic dinucleotide signaling systems, which are found ubiquitously throughout nature, allow organisms to rapidly and dynamically sense and respond to alterations in their environments. In recent years, the second messenger, cyclic di-(3',5')-adenosine monophosphate (c-di-AMP), has been identified as an essential signaling molecule in a diverse array of bacterial genera. We and others have shown that defects in c-di-AMP homeostasis result in severe physiological defects and virulence attenuation in many bacterial species. Despite significant advancements in the field, there is still a major gap in the understanding of the environmental and cellular factors that influence c-di-AMP dynamics due to a lack of tools to sensitively and rapidly monitor changes in c-di-AMP levels. To address this limitation, we describe here the development of a luciferase-based coupled enzyme assay that leverages the cyclic nucleotide phosphodiesterase, CnpB, for the sensitive and high-throughput quantification of 3'3'-c-di-AMP. We also demonstrate the utility of this approach for the quantification of the cyclic oligonucleotide-based anti-phage signaling system (CBASS) effector, 3'3'-cGAMP. These findings establish CDA-Luc as a more affordable and sensitive alternative to conventional c-di-AMP detection tools with broad utility for the study of bacterial cyclic dinucleotide physiology.

Cyclic di-GMP signaling controlling the free-living lifestyle of alpha-proteobacterial rhizobia.

Cyclic-di-GMP (c-di-GMP) is a ubiquitous bacterial second messenger which has been associated with a motile to sessile lifestyle switch in many bacteria. Here, we review recent insights into c-di-GMP regulated processes related to environmental adaptations in alphaproteobacterial rhizobia, which are diazotrophic bacteria capable of fixing nitrogen in symbiosis with their leguminous host plants. The review centers on Sinorhizobium meliloti, which in the recent years was intensively studied for its c-di-GMP regulatory network.

Spatial organization enhances versatility and specificity in cyclic di-GMP signaling.

The second messenger cyclic di-GMP regulates a variety of processes in bacteria, many of which are centered around the decision whether to adopt a sessile or a motile life style. Regulatory circuits include pathogenicity, biofilm formation, and motility in a wide variety of bacteria, and play a key role in cell cycle progression in Caulobacter crescentus. Interestingly, multiple, seemingly independent c-di-GMP pathways have been found in several species, where deletions of individual c-di-GMP synthetases (DGCs) or hydrolases (PDEs) have resulted indistinct phenotypes that would not be expected based on a freely diffusible second messenger. Several recent studies have shown that individual signaling nodes exist,and additionally, that protein/protein interactions between DGCs, PDEs and c-di-GMP receptors play an important role in signaling specificity. Additionally, subcellular clustering has been shown to be employed by bacteria to likely generate local signaling of second messenger, and/or to increase signaling specificity. This review highlights recent findings that reveal how bacteria employ spatial cues to increase the versatility of second messenger signaling.

Abstract 16003: Genetic Variation Associated With Favorable Exercise Response in Patients With Systolic Heart Failure: A Hf-action Trial Substudy

Background: Exercise has shown benefit in patients with systolic heart failure, including in the clinical trial Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION). There is heterogeneity in who derives benefit from exercise, and the biologic mechanisms of favorable response to exercise in systolic heart failure are not well understood. Hypothesis: Genetic variation is an underlying factor influencing heterogeneity in response to exercise in patients with systolic heart failure. Methods: The HF-ACTION trial randomized individuals with systolic heart failure (left ventricular ejection fraction <35%) to supervised exercise versus usual care. In this study, we performed a genome wide association study (GWAS) in the HF-ACTION biorepository using the Axiom Biobank1 genotyping array (13,403,591 single nucleotide polymorphisms [SNPs] after quality control on directly genotyped and 1000 genomes imputed data), in N=377 study subjects who completed the supervised exercise arm. Using change in peak VO2 as our outcome, we ran within-ancestry GWASes, modeling SNP effects as both additive and dominant, and conducted across-ancestry meta-analysis within each genetic model. Results: Five loci met genome-wide significance in the European ancestry analyses, 5 loci in the African ancestry, and 8 in the meta-analyses. The two most significantly associated loci across both additive and dominant meta-analysis models were rs111577308 located in the histone acetylation for transcription elongator complex 3 gene ( ELP3, p=1.212x10 -9 ) and rs75444785 located in the phosphodiesterase 4D gene ( PDE4D , p=1.565x10 -9 ). ELP3 is responsible for histone modifications related to DNA transcription factor complexes, and PDE4D is involved in cyclic AMP cell signaling. In silico analysis of these loci showed that they are in linkage with regions associated with skeletal muscle and peripheral vascular disease phenotypes. Conclusions: Using a genome-wide association study in a well-phenotyped clinical trial of exercise in systolic heart failure, we found common genetic variants in genes involved in DNA transcription histone modification and cyclic AMP cell signaling that are associated with a more favorable response to exercise.

5-hydroxymethyl-2-furaldehyde purified from Japanese pear (Pyrus pyrifolia Nakai cv. Nijisseiki) juice concentrate inhibits melanogenesis in B16 mouse melanoma cells

Pear juice concentrate prepared by boiling Japanese pear (Pyrus pyrifolia Nakai cv. Nijisseiki) juice can significantly inhibit the activity of tyrosinase, a key enzyme in melanin synthesis in human skin. Using the ethanol extract of pear juice concentrate, we homogeneously purified an active compound that was identified as 5-hydroxymethyl-2-furaldehyde (5-HMF) through 1H- and 13C-NMR and mass spectroscopy. We observed that 5-HMF inhibited the monophenolase and diphenolase activities of mushroom tyrosinase as a mixed-type inhibitor (K i values of 3.81 and 3.70mmol/L, respectively). In B16 mouse melanoma cells, treatment with 170µmol/L of 5-HMF significantly reduced α-melanocyte-stimulated melanin synthesis by suppressing the cyclic adenosine monophosphate-dependent signaling pathway involved in melanogenesis. The results of our study indicated that 5-HMF can be potentially used as a skin-lightening agent in the cosmetic industry. Abbreviations: AC: adenylate cyclase; CREB: cAMP response element-binding protein; dhFAME: S-(-)-10,11-Dihydroxyfarnesoic acid methyl ester; DMEM: dulbecco's modified eagle medium; l-DOPA: 3-(3,4-Dihydroxyphenyl)- l-alanine; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HEPES: 4-(2-Hydroxyethyl)-1-piperazine ethane sulfonic acid; 5-HMF: 5-Hydroxymethyl-2-furaldehyde; MITF: microphthalmia-associated transcription factor; α-MSH: α-Melanocyte-stimulating hormone; PKA: protein kinase A; PVDF: polyvinylidene difluoride; SDS: sodium dodecyl sulfate; TRP1: tyrosinase-related protein 1; TRP2: tyrosinase-related protein 2.

Disfunción eréctil de causa vascular

La disfunción eréctil es un grave problema de salud a nivel global, se estima que, a nivel mundial, su prevalencia para el año 2025 alcance los 322 millones de casos. Los vínculos fisiopatológicos entre la disfunción eréctil y la enfermedad cardiovascular están bien caracterizados y ambos procesos comparten la disfunción endotelial como patología común. Las dos principales explicaciones que se ofrecen están: 1. la aterosclerosis y el impacto que genera en la vía de señalización del óxido nítrico-Guanosín Monofosfato Cíclico, y 2. la hipótesis del tamaño de la arteria. En cuanto al diagnóstico, la ecografía dúplex de pene es el estudio de elección indicado siempre que se presente disfunción eréctil vascular. Con respecto al tratamiento, la farmacoterapia con Inhibidores de la fosfodiesterasa 5 ha sido ampliamente estudiada y se conocen muy bien sus indicaciones actuales.

Electrochemical detection of ascorbic acid in artificial sweat using a\xa0flexible alginate/CuO-modified electrode

A flexible sensor is presented for electrochemical detection of ascorbic acid in sweat based on single-step modified gold microelectrodes. The modification consists of electrodeposition of alginate membrane with trapped CuO nanoparticles. The electrodes are fabricated at a thin polyimide support and the soft nature of the membrane can withstand mechanical stress beyond requirements for skin monitoring. After characterization of the membrane via optical and scanning electron microscopy and cyclic voltammetry, the oxidative properties of CuO are exploited toward ascorbic acid for amperometric measurement at micromolar levels in neutral buffer and acidic artificial sweat, at ultralow applied potential (− 5 mV vs. Au pseudo-reference electrode). Alternatively, measurement of the horizontal shift of redox peaks by cyclic voltammetry is also possible. Obtaining a limit of detection of 1.97 μM, sensitivity of 0.103 V log (μM)−1 of peak shift, and linear range of 10–150 μM, the effect of possible interfering species present in sweat is minimized, with no observable cross-reaction, thus maintaining a high degree of selectivity despite the absence of enzymes in the fabrication scheme. With a lateral flow approach for sample delivery, repeated measurements show recovery in few seconds, with relative standard deviation of about 20%, which can serve to detect increased loss or absence of vitamin, and yet be improved in future by optimized device designs. This sensor is envisioned as a promising component of wearable devices for e.g. non-invasive monitoring of micronutrient loss through sweat, comprising features of light weight, low cost, and easy fabrication needed for such application.Graphical Schematic depiction of the cyclic voltammetry signal change as the sweat flows over the sensor surface.

Design of Cyclic Shifted PAM-DMT Signals in HACO-OFDM Visible Light Communication

This letter proposed a novel design of the hybrid asymmetrically clipped optical orthogonal frequency division multiplexing (HACO-OFDM) system with cyclic shifted PAM-DMT signals called CSPAM-HACO-OFDM for visible light communication. The transmitted signal generated by the CSPAM-HACO-OFDM system combines the PAM-DMT signals with cyclic shift equivalents by using even subcarriers and the ACO-OFDM signals by using odd subcarriers. Peak-to-average power ratio (PAPR) reduction with remarkably low computational complexity is achieved, and side information is not required. A near-optimal side information detector, which has a similar detection error probability as the perfect-side information detector, is used at the receiver side. Simulation results demonstrate the effectiveness of the CSPAM-HACO-OFDM system in terms of PAPR reduction and average bit error rate.

Continuous and Noninvasive Estimation of Right Ventricle Systolic Blood Pressure Using Heart Sound Signal by Deep Bidirectional LSTM Network

Objective: Timely monitoring right ventricular systolic blood pressure (RVSBP) is helpful in the early detection of pulmonary hypertension (PH). However, it is not easy to monitor RVSBP directly. The objective of this paper is to develop a deep learning technique for RVSBP noninvasive estimation using heart sound (HS) signals supported by (electrocardiography) ECG signals without complex features extraction. Methods: Five beagle dog subjects were used. The medicine U-44069 was injected into the subjects to induce a wide range of RVSBP variation. The blood pressure in right ventricle, ECG of lead I and HS signals were recorded simultaneously. Thirty-two records were collected. The relations between RVSBP and cyclic HS signals were modeled by the Bidirectional Long Short-Term Memory (Bi-LSTM) network. Results: The mean absolute error (MAE) ± standard deviation (SD) inside record was 1.85 ± 1.82 mmHg. It was 4.37 ± 2.49 mmHg across record but within subject. The corrective factors were added after training the Bi-LSTM network across subjects. Finally, the MAE ± SD from 12.46 ± 6.56 mmHg dropped to 6.37 ± 4.90 mmHg across subjects. Significance: Our work was the first to apply the Bi-LSTM network to build relations between the HS signal and RVSBP. This work suggested a noninvasive and continuous RVSBP estimation using the HS signal supported by the ECG signal by deep learning architecture without the need of healthcare professionals.

Evolutionary and functional classification of the CARF domain superfamily, key sensors in prokaryotic antivirus defense.

CRISPR-associated Rossmann Fold (CARF) and SMODS-associated and fused to various effector domains (SAVED) are key components of cyclic oligonucleotide-based antiphage signaling systems (CBASS) that sense cyclic oligonucleotides and transmit the signal to an effector inducing cell dormancy or death. Most of the CARFs are components of a CBASS built into type III CRISPR-Cas systems, where the CARF domain binds cyclic oligoA (cOA) synthesized by Cas10 polymerase-cyclase and allosterically activates the effector, typically a promiscuous ribonuclease. Additionally, this signaling pathway includes a ring nuclease, often also a CARF domain (either the sensor itself or a specialized enzyme) that cleaves cOA and mitigates dormancy or death induction. We present a comprehensive census of CARF and SAVED domains in bacteria and archaea, and their sequence- and structure-based classification. There are 10 major families of CARF domains and multiple smaller groups that differ in structural features, association with distinct effectors, and presence or absence of the ring nuclease activity. By comparative genome analysis, we predict specific functions of CARF and SAVED domains and partition the CARF domains into those with both sensor and ring nuclease functions, and sensor-only ones. Several families of ring nucleases functionally associated with sensor-only CARF domains are also predicted.

Abstract 545: Sex Difference in Right Ventricular Response to Pressure Overload is Associated With Differential Fibrotic Remodeling and Cyclic Guanosine Monophosphate Signaling

Background: In HFpEF and PAH, men are more likely than women to develop right ventricular dysfunction (RVD) and die. Mechanisms underlying these sex differences are not well understood. In advanced HF patients, RVD is associated with RV fibrosis. Sex differences in cGMP anti-fibrotic cardioprotection have been reported. Hypothesis: Sex differences in RV response to pressure overload may be due to differential anti-fibrotic cGMP signaling in the RV. Methods: Adult male and female C57BL6/J mice underwent pulmonary artery banding (PAB, 25g) vs. thoracotomy (Sham). RV remodeling was assessed by echocardiography, pressure-volume loop recordings, morphometrics, and histology. Expression of transcripts encoding various cGMP signaling proteins ( Nppa, Nppb, Npr1, Npr2, Npr3, Gucy1a3, Gucy1b3, Pde5, Pde9a, Pkg1a ), the fetal gene program, tissue fibrosis and ECM remodeling ( Ace, Tgfβs, Smads, Ctgf, αSma, Postn, Col1α1, Lum, Igfbp5, Mmp2-3, Timp1-2) were assessed at 9wks. Results: Post-PAB survival rate did not differ between sexes (log-rank HR 1.02, 95% CI 0.30-3.48, P=NS), but median time-to-death was 20 days (IQR 15-32) for M-PAB vs. 35.5 days (IQR 10.8-41.5) for F-PAB. PAB increased RV mass in both sexes (Fulton’s index 0.45±0.07 M-PAB vs 0.21±0.01 M-Sham, P<0.01; 0.49±0.06 F-PAB vs 0.22±0.01 F-Sham, P<0.01). RV myocyte hypertrophy was greater in M-PAB (cardiomyocyte area 592.7±6μm 2 vs 397.7±21.6μm 2 F-PAB, P<0.01). RV dilation and decreased TAPSE and RV S’ were present in all PAB mice. Only M-PAB had depressed RV FAC (29.9±1.9% vs. 38.1±2.4% F-PAB, P=0.02). M-PAB had worse diastolic function than F-PAB (Tau 32.8±2.9ms M-PAB vs 14.2±2.1ms M-Sham, P<0.01; 25.6±5.3ms F-PAB vs 15.0±2.1ms M-Sham, P=NS). In male but not female mice, PAB induced upregulation of Nppa, Nppb, Npr1, Npr2, Npr3, Gucy1a3, Gucy1b3, Pde5 and Pkg1a in the RV. RV transcript levels of Ace, Col1α1, Ctgf, Igfbp5, Mmp2, and Timp2 were also higher in M-PAB than F-PAB. Conclusions: Males have worse RV functional response to PAB than do females. This sex difference was also associated with increased mRNA levels of cGMP signaling mediators and upregulation of pro-hypertrophic and pro-fibrotic genes in male PAB mice. Further studies are needed to elucidate sex-dependent regulation of RV remodeling.