Functional Adaptation Research Articles

Distribution of Polyphosphate Kinase 2 Genes in Bacteria Underscores a Dynamic Evolutionary History.

Polyphosphate kinase 2 (PPK2) enzymes catalyze phosphoryl transfer from polyphosphate to nucleotides and are divided into three classes, each presumed to have different catalytic preferences. With relevance to biotechnology, medicine, and primitive biology, there is significant interest in understanding the evolutionary history of PPK2 enzymes and predicting their functional properties. We reasoned that the distribution and pairing preferences of PPK2 gene classes across the prokaryote tree of life may shed light on these questions. PPK2 was found to be a dynamic gene family, often present in only a subset of species within a clade, even when considering a single genus. Although all possible PPK2 pairs were observed, a ~2-fold enrichment for Class I enzymes in species with multiple PPK2 genes strongly shapes pairing preferences. PPK2 class preference in the absence of PPK1, which synthesizes rather than utilizes polyphosphate, indicates the potential for functional adaptation and/or promiscuity with respect to reaction directionality for all classes, a feature that has previously been associated only with Class I. Patterns of adjacent PPK2 genes revealed signatures of gene duplication, as adjacent genes overwhelmingly belonged to the same class, as well as the potential for an added layer of PPK2 dynamics: hetero-oligomerization of single-domain Class II enzymes to recapitulate the structure of two-domain Class II enzymes. Finally, an updated PPK2 tree constructed from domains instead of genes calls into question established narratives of PPK2 evolution, putting new limits on the extent to which nucleobase promiscuity can be invoked in the early evolution of this family.

Temporal Effects of Hypoxia Exposure at High Altitudes on Compensatory Brain Function: Evidence from Functional Connectivity of Resting-State EEG Brain Networks.

Ren, Hong, Xi-Yue Yang, Rui Su, HaiLin Ma, and Hao Li. Temporal Effects of Hypoxia Exposure at High Altitudes on Compensatory Brain Function: Evidence from Functional Connectivity of Resting-State EEG Brain Networks. High Alt Med Biol. 00:00-00, 2024. Background: The aim of this study was to investigate the effects of prolonged exposure to hypobaric hypoxia at high altitude on changes in brain function measured by electroencephalography (EEG), focusing specifically on the resting-state brain network functional connectivity and compensatory adaptations in brain function among individuals with varying durations of high altitude residency. Methods: In study I, 64 participants were divided into high-altitude group (HG) and low-altitude group (LG). Ninety-six long-term migrants residing at an altitude of 3,650 m were recruited for studyII and categorized into three groups based on their duration of stay at high altitude: group A (1-2 years), group B (8-10 years), and group C (18-20 years). Resting-state EEG data were collected from each participant, and functional connectivity analysis was conducted using Phase Locking Value. Results: Study I showed that participants with HG had stronger functional connectivity in the occipital lobe than those with LG (p < 0.05). The study II findings indicate that there were significant differences in functional connectivity strength among the frontal and occipital lobes in groups A, B, and C across the α, β, δ, and θ frequency bands. Specifically, the functional connectivity strength of the frontal lobe was significantly higher in group A compared with group B, and in group B compared with group C (p < 0.05). Additionally, the functional connectivity of the occipital lobe was significantly higher in group C compared with group B, and in group B compared with group A (p < 0.05). Conclusions: The consistent results of the whole frequency band suggest that the individual's occipital lobe function is enhanced to compensate for the damage of frontal lobe function, so as to better adapt to the extreme environment at high altitude.

MAIT cell plasticity enables functional adaptation that drives antibacterial immune protection.

Mucosal-associated invariant T (MAIT) cells are known for their rapid effector functions and antibacterial immune protection. Here, we define the plasticity of interferon-γ (IFN-γ)-producing MAIT1 and interleukin-17A (IL-17A)-producing MAIT17 cell subsets in vivo. Whereas T-bet+ MAIT1 cells remained stable in all experimental settings, after adoptive transfer or acute Legionella or Francisella infection, RORγt+ MAIT17 cells could undergo phenotypic and functional conversion into both RORγt+T-bet+ MAIT1/17 and RORγt-T-bet+ MAIT1 cells. This plasticity ensured that MAIT17 cells played a dominant role in generating antibacterial MAIT1 responses in mucosal tissues. Single-cell transcriptomics revealed that MAIT17-derived MAIT1 cells were distinct from canonical MAIT1 cells yet could migrate out of mucosal tissues to contribute to the global MAIT1 pool in subsequent systemic infections. Human IL-17A-secreting MAIT cells also showed similar functional plasticity. Our findings have broad implications for understanding the role of MAIT cells in combatting infections and their potential utility in MAIT cell-targeted vaccines.

Differential timing of mitochondrial activation in rat dorsal striatum induced by procedural learning and swimming.

Stressful experiences form stronger memories due to enhanced neural plasticity mechanisms linked to glucocorticoid hormones (cortisol in humans, corticosterone in rats). Among other neural structures, the dorsal striatum plays a role in the corticosterone-induced consolidation of stressful memories, particularly in the cued water maze task. Neural plasticity is related to mitochondrial activity due to the relevance of energy production and signaling mechanisms for functional and morphological neuronal adaptations. Corticosterone has been shown to enhance brain mitochondrial activity by activating glucocorticoid receptors. In this context, striatum functions are susceptible to change in relation to mitochondrial responses. Based on this evidence, we hypothesized that training in the cued water maze would induce an increase in corticosterone levels and mitochondrial activity (mitochondrial membrane potential and calcium content) in the dorsal striatum, and that these adaptations might be related to memory consolidation of the task. We used an ELISA assay to evaluate plasma and striatal corticosterone levels; mitochondrial activity was determined with the florescent probes MitoTracker Red (mitochondrial membrane potential) and Rhod-2 (calcium content) in brain slices containing the dorsal striatum of rats trained in the cued water maze and euthanized at different times after training (0.5, 1.5, or 6.0 h). We also analyzed the effect of post-training inhibition of striatal mitochondrial activity by OXPHOS complex 1 inhibitor rotenone, on the consolidation of the cued water maze task. We found that cued water maze training induced an increase in corticosterone levels and a time-dependent elevation of mitochondrial membrane potential and mitochondrial calcium content in the dorsal striatum. Unexpectedly, rotenone administration facilitated the retention test. Altogether, our results suggest that enhanced mitochondrial activity in the dorsal striatum is relevant for cued water maze consolidation. The increase in mitochondrial activity was contextually associated with an elevation of corticosterone in plasma and the dorsal striatum. Additionally, our swimming groups also showed an increase in mitochondrial activity in the dorsal striatum, but with a different pattern, which could suggest a differential functional adaptation in this structure.

Wireless Modular Implantable Neural Device with One-touch Magnetic Assembly for Versatile Neuromodulation.

Multimodal neural interfaces open new opportunities in brain research by enabling more sophisticated and systematic neural circuit dissection. Integrating complementary features across distinct functional domains, these multifunctional neural probes have greatly advanced the interrogation of complex neural circuitry. However, introducing multiple functionalities into a compact form factor for freely behaving animals presents substantial design hurdles that complicate the device or require more than one device. Moreover, fixed functionality poses challenges in meeting the dynamic needs of chronic neuroscience inquiry, such as replacing consumable parts like batteries or drugs. To address these limitations, the modular implantable neural device (MIND) is introduced with a one-touch magnetic assembly mechanism. Leveraging the seamless exchange of neural interface modules such as optical stimulation, drug delivery, and electrical stimulation, MIND ensures functional adaptability, reusability, and scalability. The versatile design of MIND will facilitate brain research by enabling simplified access to multiple functional modalities as needed.

Molecular pathways of osmoregulation in response to salinity stress in the gills of the scalloped spiny lobster (Panulirus homarus) within survival salinity

Scalloped spiny lobster (Panulirus homarus) aquaculture is the preferred strategy to resolve the conflict between supply and demand for lobster. Environmental conditions, such as salinity, are key to the success of lobster aquaculture. However, physiological responses of P. homarus to salinity stress have not been well studied. This study investigated the gill histology, osmoregulation and gill transcriptome of the early juvenile P. homarus (weight 19.04 ± 3.95 g) cultured at salinity 28 (control), 18, and 38 for 6 weeks. The results showed that the gill filaments of P. homarus exposed to low salinity showed severe separation of the cuticle and epithelial cells due to water absorption and swelling, as well as the dissolution and thinning of the cuticle and the rupture of the septum that separates the afferent and efferent channels. The serum osmolarity of P. homarus varied proportionately with external medium salinity and remained consistently above ambient osmolarity. The serum Na+, Cl−, K+, and Mg2+ concentrations P. homarus exhibited a pattern similar to that of serum osmolality, while the concentration of Ca2+ remained unaffected at salinity 18 but significantly increased at salinity 38. Gill Na+/K+-ATPase activity of P. homarus increased (p < 0.05) under the both salinity stress. Salinity 18 significantly increased Glutamate dehydrogenase (GDH) and Glutamicpyruvic transaminase (GPT) activity in the hepatopancreas of P. homarus (p < 0.05). According to transcriptome analysis, versus control group (salinity 28), 929 and 1095 differentially expressed genes (DEGs) were obtained in the gills of P. homarus at salinity 18 and 38, respectively, with these DEGs were mainly involved in energy metabolism, transmembrane transport and oxidative stress and substance metabolism. In addition, the expression patterns of 8 key DEGs mainly related to amino acid metabolism, transmembrane transport and oxidative stress were verified by quantitative real-time PCR (RT-qPCR). The present study suggests that salinity 18 has a greater impact on P. homarus than salinity 38, and P. homarus demonstrates effective osmoregulation and handle with salinity fluctuations (18 to 38) through physiological and functional adaptations. This study provides an improved understanding of the physiological response strategies of P. homarus facing salinity stress, which is crucial for optimizing aquaculture practices for this species.

Adaptation of Left Ventricular Function and Myocardial Microstructure in Fetuses with Right Ventricular Hypoplasia

Adaptation of Left Ventricular Function and Myocardial Microstructure in Fetuses with Right Ventricular Hypoplasia

Molecular and functional adaption of Arabidopsis villins.

Villins are versatile, multifunctional actin regulatory proteins. They promote actin stabilization and remodeling mainly via their actin bundling and Ca2+-dependent severing activities, respectively. Arabidopsis subclass II and III villins normally coexist in cells, but the biological significance of their coexistence remains unknown. Here we demonstrate that subclass II villin binds to Ca2+ with high affinity and exhibits strong severing but weak bundling activity compared to subclass III villin. Subclass II villin plays a dominant role in promoting actin remodeling, which requires its Ca2+-dependent severing activity. Subclass II villin is also strictly required for physiological processes including oriented organ growth and stress tolerance. By comparison, subclass III villin binds to Ca2+ with low affinity and exhibits weak severing but strong bundling activity, and acts as the major player in controlling actin stabilization and organization. Thus, we demonstrate that multifunctional villin isovariants have diverged biochemically to ensure exquisite control of the actin cytoskeleton to meet different cellular needs in plants. This study provides new insights into the role of villins in fine-tuning actin dynamics and plant development.

The sperm hook as a functional adaptation for migration and self-organized behavior.

In most murine species, spermatozoa exhibit a falciform apical hook at the head end. The function of the sperm hook is not yet clearly understood. In this study, we investigate the role of the sperm hook in the migration of spermatozoa through the female reproductive tract in Mus musculus (C57BL/6), using a deep tissue imaging custom-built two-photon microscope. Through live reproductive tract imaging, we found evidence indicating that the sperm hook aids in the attachment of spermatozoa to the epithelium and facilitates interactions between spermatozoa and the epithelium during migration in the uterus and oviduct. We also observed synchronized sperm beating, which resulted from the spontaneous unidirectional rearrangement of spermatozoa in the uterus. Based on live imaging of spermatozoa-epithelium interaction dynamics, we propose that the sperm hook plays a crucial role in successful migration through the female reproductive tract by providing anchor-like mechanical support and facilitating interactions between spermatozoa and the female reproductive tract in the house mouse.

3D printing as assistive technology for individuals with deafblindness: perspectives of rehabilitation professionals

There is a growing body of evidence on practical applications of three-dimensional (3D) printing to support the rehabilitation of individuals with sensory impairments. However, applications in the field of deafblindness, or the combination of vision and hearing impairment, remain scarce. Therefore, the present study aimed to explore actual and potential applications of 3D printing in deafblindness rehabilitation from the perspective of rehabilitation professionals in two focus group discussions that involved orientation and mobility specialists, vision rehabilitation specialists, audiologists, and braille technicians. Participants exchanged on 1) 3D printing applications to address their clients’ rehabilitation needs, 2) factors that can impact its integration into their practice, and 3) the ideal logistics for producing and delivering 3D printed products. Educative models and functional adaptations were identified to improve communication, learning, mobility, and independent living skills for individuals with deafblindness. Professionals agreed that the main barriers limiting 3D printing adoption were linked to time constraints and insufficient awareness or knowledge about this technology, while the most crucial facilitator was the promotion of interdisciplinary collaborations with 3D printing experts. The present findings thus emphasize the need for global collaborations, knowledge dissemination, and ongoing research and validation of 3D printing applications to support individuals with deafblindness.

Endurance Exercise Training Alters Lipidomic Profiles of Plasma and Eight Tissues in Rats: a MoTrPAC study.

Endurance exercise training (ExT) induces metabolic, structural, and functional adaptations via lipidomic modifications, yet the systematic elucidation of lipidome alterations in response to ExT remains incomplete. As a part of the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we leveraged non-targeted and targeted lipidomics for the systematic discovery of lipid alterations in the brown adipose tissue, heart, hippocampus, kidney, liver, lung, skeletal muscle gastrocnemius, subcutaneous white adipose tissue, and plasma in response to 1, 2, 4 or 8 weeks of ExT in 6-month-old male and female Fischer-344 rats. This study demonstrates that these tissues, each with distinct lipidomic features, underwent dynamic, sexually dimorphic lipid remodeling. Exercise trained animals showed reduced whole-body adiposity and improved cardiorespiratory fitness, along with enhanced utilization of lipid stores and dynamic triacylglycerol remodeling compared to sedentary controls in all tissues except hippocampus. They also showed modifications in phospholipids, lysophospholipids, oxylipins, and ceramides in several tissues. Coordinated changes across tissues reflect systemic tissue communication, with liver-plasma-heart connection potentially playing a key role in systemic lipid metabolism during ExT. These data will improve our understanding of lipid-associated biological processes underlying the health-promoting benefits of ExT.

Muscular robusticity and strength in the lower extremities in elite handball players

The relationship between structural and functional of parameters of skeletal muscles in young athletes needs further observations. The analyses of their age-group differences, sexual dimorphism, asymmetry characteristics in body regions, in sports having different pattern of physical loading could serve important information in this topic. 175 elite Hungarian handball players aged between 14 and 21 years were examined in 2023. Muscle mass component of the body segments was estimated by DEXA method and muscle thickness of the anterior mid-thigh region was measured by a new ultrasonic technique. The strength of knee extensor muscles was assessed by using an isokinetic protocol (Kineosystem dynamometer). A strong association between muscle robusticity and strength in the thigh region was confirmed in males, but not in females. Asymmetry in muscle mass reflected in the asymmetry in the knee extensor strength. A new predictive equation of muscle mass in the jumping leg and the total body from the muscle thickness in the anterior mid-thigh region of jumping leg was introduced. The exploration and understanding of asymmetric structural and functional adaptations can help athletes and trainers in planning the training and training interventions to reduce the risk of injuries.

Functional dynamics analysis of endophytic microbial communities during Amorphophallus muelleri seed maturation

Konjac seeds of Amorphophallus muelleri are produced through a unique form of apomixis in triploid parthenogenesis, and typically require a longer maturation period (approximately 8 months). To date, the relevant functions of endophytic microbial taxa during A. muelleri seed development and maturation remain largely unexplored. In this study, we analyzed the functional adaptability and temporal dynamics of endophytic microbial communities during three stages of A. muelleri seed maturation. Through metagenomic sequencing, we determined that the functions of the endophytic microbiome in A. muelleri seeds were driven by the seed maturation status, and the functions of the microbial communities in the seed coats and seeds differed significantly. The species annotation results show that Proteobacteria, Actinobacteria, Ascomycota, and Basidiomycota were the dominant bacterial and fungal communities in A. muelleri seeds at different maturation stages. The KEGG and COG functional gene annotation results revealed that the seed samples during the three maturation stages had higher KO functional diversity than the seed coat samples, and the COG functional diversity of the green and red seed samples was also significantly higher than that of the seed coat samples. At different maturation stages, microbial functional genes involved in energy production and conversion as well as carbon fixation were enriched in the A. muelleri seed coats, while microbial functional genes involved in signal transduction mechanisms, amino acid transport and metabolism, carbohydrate metabolism, and lipid metabolism were more highly expressed in the seeds. Moreover, in the middle to late stages of seed maturation, the microbial functional genes involved in the biosynthesis of resistant compounds such as phenols, flavonoids, and alkaloids were significantly enriched to enhance the resistance and environmental adaptation of A. muelleri seeds. The results verified that the functions of the endophytic microbial communities change dynamically during A. muelleri seed maturation to adapt to the current needs of the host plant, which has significant implications for the exploration and utilization of functional microbial resources in A. muelleri seeds.

Can Transcriptomics Elucidate the Role of Regulation in Invasion Success?

When a species invades a novel environment, it must bridge the environment-phenotype mismatch in its new range to persist. Contemporary invasion biology research has focused on the role that trait variation and adaptation, and their underlying genomic factors, play in a species' adaptive potential, and thus facilitating invasion. Empirical studies have provided valuable insights into phenotypes that persist and arise in novel environments, coupled with 'omics tools that further the understanding of the contributions of genomic architecture in species establishment. Particularly, the use of transcriptomics to explore the role of plasticity in the initial stages of an invasion is growing. Here, we assess the role of various mechanisms relating to regulation and functional adaptation (often measured via the transcriptome) that support trait-specific plasticity in invasive species, allowing phenotypic variability without directly altering genomic diversity. First, we present a comprehensive review of the studies utilising transcriptomics in invasion biology. Second, we collate the evidence for and against the role of a range of regulatory processes in contributing to invasive species plasticity. Finally, we pose open questions in invasion biology where the use of transcriptome data may be valuable, as well as discuss the methodological limitations.

Biology and mechanobiology of the intervertebral disc : Challenges for regenerative therapies

The fibrocartilaginous intervertebral discs between the vertebrae give the spine mobility and flexibility. Age and degeneration contribute to tissue changes that affect the composition and structure of the intervertebral discs and can lead to loss of function and back pain. The intervertebral disc cells are responsible for the formation and maintenance of the tissue and are influenced by the physiological load. Degenerative changes that promote tissue degradation are influenced by cellular responses to overuse, inflammation and nutrient deficiency. The mechanobiology of intervertebral discs deals with the interrelationships of the functional adaptation of this organ down to the cellular and molecular level and contributes to the understanding of the causes and consequences of degeneration. Based on these findings, the challenges for suitable regenerative therapy concepts can be understood.

Unique insights into morphological characterization and functional adaptation of the scaly shank skin in aquatic and terrestrial birds

The avian skin is a vital barrier against external effects and undergoes modification to adapt to the different ecosystems. The current study focused on the comprehensive study of the scaly shank skin of aquatic birds, Egyptian Balady Duck (EBD) as well as terrestrial birds, Broad Breasted White Turkey (BBWT) via gross anatomy, histology, and scanning electron microscopy with ED-XRF analysis. The shank skin color was yellow to black in EBD and creamy-white in BBWT. Gross anatomy exhibited two types of scales around the shank: scute and scutella scales in EBD and four types: scute, scutella, reticula, and cancella (interstitial) scales in BBWT. Most scales were non-overlapped and separated by sulci in both birds except those on the dorsum of the shank of BBWT. SEM of the descaled skin revealed an irregular surface due to keratinocytes defining a polygonal texture in EBD and Langerhans cells (a large oval-shaped cell body with abundant long projections) attached to neighboring keratinocytes in BBWT. Histologically, the epidermal and dermal layers varied among the different skin aspects of the shanks of both birds. Langerhans cells were seen within the basal cell layer of the stratum germinativum and collagen fibers of the dermal stratum superficiale. Melanocytes were observed in the stratum basale in EBD. In both birds, abundant telocytes and fibroblasts were distributed within the dermal layers, with excessive adipose tissue in the dermis of the shank skin of EBD. According to the results of the ED-XRF analysis of the scaly shank skin, elements and oxides were present in both species. In conclusion, the findings of the present study reflect the correlations between the functional morphology of shank skin and the bird habitats.

Pathogenic proteotoxicity of cryptic splicing is alleviated by ubiquitination and ER-phagy.

RNA splicing enables the functional adaptation of cells to changing contexts. Impaired splicing has been associated with diseases, including retinitis pigmentosa, but the underlying molecular mechanisms and cellular responses remain poorly understood. In this work, we report that deficiency of ubiquitin-specific protease 39 (USP39) in human cell lines, zebrafish larvae, and mice led to impaired spliceosome assembly and a cytotoxic splicing profile characterized by the use of cryptic 5' splice sites. Disruptive cryptic variants evaded messenger RNA (mRNA) surveillance pathways and were translated into misfolded proteins, which caused proteotoxic aggregates, endoplasmic reticulum (ER) stress, and, ultimately, cell death. The detrimental consequence of splicing-induced proteotoxicity could be mitigated by up-regulating the ubiquitin-proteasome system and selective autophagy. Our findings provide insight into the molecular pathogenesis of spliceosome-associated diseases.

Delineating early life stages of Belone belone: analysis of external morphology and postcranial skeletal development of the garfish

During fish larvae development functional, morphological, and physiological adaptations are key in larval survival strategies and can determine mortality bottlenecks. For many fish groups such as needlefish, which play crucial roles in marine food webs, studies on early life stages are almost lacking. Herein, the development, with focus on the postcranial skeleton, of the garfish Belone belone (Linnaeus, 1761) is described and a staging system is introduced. Ten larval and juvenile life stages are proposed in three main phases: yolk sac, larval, and juvenile development. During the yolk sac phase the garfish deplete their yolk reservoirs and finish the development of their unpaired fins. During the larval period the lower jaw elongates and the needlenose stage is reached. In the juvenile phase, the upper jaw elongates until both jaws are almost equally long. Since B. belone larvae develop much of their postcranial skeleton in the late embryonic and yolk sac phases they might not experience a severe bottleneck in this early stage such as many other marine fish species. Therefore, young garfish could be more resilient to environmental changes.

Abstract 4135001: Right Ventricular Function and Right Ventricular-Pulmonary Arterial Adaptations in Aging Older Adults

Background: Compared to our understanding of left ventricular (LV) dysfunction in cardiac aging, there is far less depiction of right heart function, especially right ventricular (RV) remodelling in response to pulmonary arterial (PA) changes with aging. Given the importance of cardio-respiratory function in declining aerobic capacity with age, identifying sensitive metrics of RV function would complete our understanding of RV and RV-PA conduit adaptations in aging. Methods: Community older adults without cardiovascular disease underwent prospective cardiac magnetic resonance (CMR) imaging that measured RV volumes (RV end-diastolic volume, EDV; end-systolic volume, ESV), RV function (RV ejection fraction, RVEF; RV global longitudinal strain, GLS) and RV-PA coupling (end-systolic elastance to arterial elastance, computed as ratio of LV stroke volume, SV to RVESV). A RV-PA coupling threshold of &gt;1.5 (based on prior literature) implies effective RV adaptation Aerobic capacity (VO 2 ) was calculated. Multivariable regression adjusted for significant covariates. Results: We studied 251 participants (54.5% female, 70.78±9.07 years) with normal LV and RV function (mean LVEF, 65.13±7.51 %, RVEF, 64.25±6.98 %). RV-PA threshold of &lt;1.5 defined poorer RV structure and function with lower RVEF (56.6 ± 3.95 vs. 67.5 ± 5.25, p &lt; 0.001), RVGLS (28.13± 4.55 vs. 32.8 ± 5.1, p = 0.0065) and higher RVEDV index (73.2 ± 15.15 vs. 63.34 ± 12.03, p &lt; 0.001), compared to those with RVPA &gt; 1.5. Predictors of better RVGLS were female sex (β=0.189, adj. p=0.019), independent of systolic and diastolic blood pressure while predictors of RVESV were female sex (β=-0.433, adj. p&lt;0.00), age (β=-0.195, adj. p&lt;0.001) and body mass index (β=0.264, adj. p&lt;0.001). Overall, women had better RVEF and RVGLS but lower RVSV and VO 2 (30.1±4,5 vs 37.7±5.1, ml/kg/min) compared to men (all p&lt;0.001) (Table 1). Lower VO 2 among women compared to men was accompanied by higher RV-PA (2.1±0.7 vs 1.8±0.7, p&lt;0.001). Female sex (β=0.233, 95% CI [0.158, 0.506, adj. p&lt;0.001) was independently associated with RV-PA coupling on multivariable analyses. Conclusions: Novel CMR-derived right heart parameters defined RV function and RV adaptations as depicted by RV-PA interactions in older adults. Superior RV functions and RV-PA coupling in women may represent hemodynamic adaptations in women, despite lower aerobic capacities.

Abstract 4142768: Association Between Right Ventricular-Pulmonary Arterial Coupling and Outcomes in Patients with Heart Failure with Preserved Ejection Fraction

Introduction: Right ventricle (RV)-pulmonary artery (PA) coupling reflects functional adaptation of RV to afterload. Impaired RV-PA coupling is associated with worse outcomes in patients with pulmonary hypertension. However, the association between RV-PA coupling and outcomes in patients with heart failure with preserved ejection fraction (HFpEF) is not well established. Objective: To assess the association between RV-PA coupling and outcomes in patients with HFpEF and determine an optimal cutpoint of the TAPSE/RVSP ratio for prediction of adverse events. Methods: Participants with a diagnosis of HFpEF were enrolled at the University of Toledo Medical Center from March 2012 and were followed until August 2023. The ratio of tricuspid annular plain systolic excursion (TAPSE) to right ventricular systolic pressure (RVSP) on echocardiogram was used as a measure of RV-PA coupling. The primary endpoint was death or heart failure hospitalization. ROC analysis was performed to determine an optimal cutpoint point for TAPSE/RVSP. Cox proportional hazards regression model was used to assess the association between TAPSE/RVSP and outcomes. Results: 83 participants (age 68.69 ± 10.72, 67.5% female) with HFpEF and available echocardiogram data were enrolled in the study. The median TAPSE/RVSP was 0.41. Death or heart failure hospitalization occurred in 51 (56.6%) individuals. Using ROC curve analysis, we identified the optimal cutpoint of TAPSE/RVSP of 0.31 which had a sensitivity of 57% and specificity of 88% for predicting mortality (AUC 0.756, 0.622-0.889). TAPSE/RVSP less than 0.31 was associated with higher risk of death or heart failure (HF) hospitalization (HR=2.61, CI=1.28-5.33, p= 0.008), death (HR=3.40, CI=1.34-8.64, p= 0.01), and HF hospitalization (HR=2.45, CI=1.06-5.68, p= 0.03). Conclusion: Worse RV-PA coupling was associated with worse outcomes in individuals with HFpEF. The TAPSE/RVSP cutpoint of &lt;0.31 had a good specificity for prediction of adverse events including death or HF hospitalization.