Search

The M2 proton channel aids in the exit of mature influenza viral particles from the host plasma membrane through its ability to stabilize regions of high negative Gaussian curvature (NGC) that occur at the neck of budding virions. The channels are homo-tetramers that contain a cytoplasm-facing amphipathic helix (AH) that is necessary and sufficient for NGC generation; however, constructs containing the transmembrane spanning helix, which facilitates tetramerization, exhibit enhanced curvature generation. Here, we used all-atom molecular dynamics (MD) simulations to explore the conformational dynamics of M2 channels in lipid bilayers revealing that the AH is dynamic, quickly breaking the fourfold symmetry observed in most structures. Next, we carried out MD simulations with the protein restrained in four- and twofold symmetric conformations to determine the impact on the membrane shape. While each pattern was distinct, all configurations induced pronounced curvature in the outer leaflet, while conversely, the inner leaflets showed minimal curvature and significant lipid tilt around the AHs. The MD-generated profiles at the protein–membrane interface were then extracted and used as boundary conditions in a continuum elastic membrane model to calculate the membrane-bending energy of each conformation embedded in different membrane surfaces characteristic of a budding virus. The calculations show that all three M2 conformations are stabilized in inward-budding, concave spherical caps and destabilized in outward-budding, convex spherical caps, the latter reminiscent of a budding virus. One of the C2-broken symmetry conformations is stabilized by 4 kT in NGC surfaces with the minimum energy conformation occurring at a curvature corresponding to 33 nm radii. In total, our work provides atomistic insight into the curvature sensing capabilities of M2 channels and how enrichment in the nascent viral particle depends on protein shape and membrane geometry.

Abstract Aging is associated with cardiac contractile abnormalities, but the etiology of these contractile deficits is unclear. We hypothesized that cardiac contractile and regulatory protein expression is altered during aging. To investigate this possibility, left ventricular (LV) lysates were prepared from young (6 months) and old (24 months) Fischer344 rats. There are no age‐related changes in SERCA2 expression or phospholamban phosphorylation. Additionally, neither titin isoform expression nor phosphorylation differed. However, there is a significant increase in β‐isoform of the myosin heavy chain (MyHC) expression and phosphorylation of TnI and MyBP‐C during aging. In permeabilized strips of papillary muscle, force and Ca2+ sensitivity are reduced during aging, consistent with the increase in β‐MyHC expression and TnI phosphorylation. However, the increase in MyBP‐C phosphorylation during aging may represent a mechanism to compensate for age‐related contractile deficits. In isolated cardiomyocytes loaded with Fura‐2, the peak of the Ca2+ transient is reduced, but the kinetics of the Ca2+ transient are not altered. Furthermore, the extent of shortening and the rates of both sarcomere shortening and re‐lengthening are reduced. These results demonstrate that aging is associated with changes in contractile and regulatory protein expression and phosphorylation, which affect the mechanical properties of cardiac muscle.

Introduction: Vasodilatation in response to NO is a fundamental response of the vasculature, and during aging, the vasculature is characterized by an increase in stiffness and decrease in sensitivity to NO mediated vasodilatation. Vascular tone is regulated by the activation of smooth muscle and nonmuscle (NM) myosin, which are regulated by the activities of myosin light chain kinase (MLCK) and MLC phosphatase. MLC phosphatase is a trimeric enzyme with a catalytic subunit, myosin targeting subunit (MYPT1) and 20 kDa subunit of unknown function. Alternative mRNA splicing produces LZ+/LZ- MYPT1 isoforms and the relative expression of LZ+/LZ- MYPT1 determines the sensitivity to NO mediated vasodilatation. This study tested the hypothesis that aging is associated with changes in LZ+ MYPT1 and NM myosin expression, which alter vascular reactivity.Methods: We determined MYPT1 and NM myosin expression, force and the sensitivity of both endothelial dependent and endothelial independent relaxation in tertiary mesenteric arteries of young (6mo) and elderly (24mo) Fischer344 rats.Results: The data demonstrate that aging is associated with a decrease in both the expression of NM myosin and force, but LZ+ MYPT expression and the sensitivity to both endothelial dependent and independent vasodilatation did not change. Further, smooth muscle cell hypertrophy increases the thickness of the medial layer of smooth muscle with aging.Discussion: The reduction of NM myosin may represent an aging associated compensatory mechanism to normalize the stiffness of resistance vessels in response to the increase in media thickness observed during aging.

Abstract Sodium-dependent glucose transporters (SGLTs) couple a downhill Na+ ion gradient to actively transport sugars. Here, we investigate the impact of the membrane potential on vSGLT structure and function using sugar uptake assays, double electron-electron resonance (DEER), electrostatic calculations, and kinetic modeling. Negative membrane potentials, as present in all cell types, shift the conformational equilibrium of vSGLT towards an outward-facing conformation, leading to increased sugar transport rates. Electrostatic calculations identify gating charge residues responsible for this conformational shift that when mutated reduce galactose transport and eliminate the response of vSGLT to potential. Based on these findings, we propose a comprehensive framework for sugar transport via vSGLT, where the cellular membrane potential facilitates resetting of the transporter after cargo release. This framework holds significance not only for SGLTs but also for other transporters and channels.

The decay of the electrical energy in a resistor-vacuum capacitor circuit is shown to involve multiple relaxation processes, with dramatically different time constants. This is measured using a vacuum capacitor to eliminate the effect of a dielectric between the plates (polypropylene capacitors are shown to exhibit similar behavior). A simple phenomenological model accounts for this behavior in spite of the difficulty in applying Maxwell's equations to such a circuit. These results will lead to a revision of our understanding of the physics of circuits, having particular impact on applications that use capacitors as sensors in collecting precision data (such as found in quantum measurements and dielectric spectroscopy).

Drug resistance can evolve from a subpopulation of cancer cells that initially survive drug treatment and then gradually form a pool of drug-tolerant cells. Several studies have pinpointed the activation of a specific bypass pathway that appears to provide the critical therapeutic target for preventing drug tolerance. Here, we take a systems-biology approach, using proteomics and genomics to examine the development of drug tolerance to EGFR inhibitors in EGFR-mutant lung adenocarcinoma cells and BRAF inhibitors in BRAF-mutant melanoma cells. We found that there are numerous alternative mitogenic pathways that become activated in both cases, including YAP, STAT3, IGFR1, and phospholipase C (PLC)/protein kinase C (PKC) pathways. Our results suggest that an effective therapeutic strategy to prevent drug tolerance will need to take multiple alternative mitogenic pathways into account rather than focusing on one specific pathway.

Introduction: MET amplification is a known resistance mechanism to EGFR tyrosine kinase inhibitor (TKI) treatment in EGFR-mutant NSCLC. Dual EGFR-MET inhibition has been reported with success in overcoming such resistance and inducing clinical benefit. Resistance mechanisms to dual EGFR-MET inhibition require further investigation and characterization. Methods: Patients with NSCLC with both MET amplification and EGFR mutation who have received crizotinib, capmatinib, savolitinib, or tepotinib plus osimertinib (OSI) after progression on OSI at MD Anderson Cancer Center were included in this study. Molecular profiling was completed by means of fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS). Radiological response was assessed on the basis of Response Evaluation Criteria in Solid Tumors version 1.1. Results: From March 2016 to March 2022, 23 treatments with dual MET inhibitor and osi were identified with a total of 20 patients included. Three patients received capmatinib plus OSI after progression on crizotinib plus OSI. Median age was 64 (38–89) years old and 75% were female. MET amplification was detected by FISH in 14 patients in the tissue, NGS in 10 patients, and circulating tumor DNA in three patients. Median MET gene copy number was 13.6 (6.4–20). Overall response rate was 34.8% (eight of 23). In assessable patients, tumor shrinkage was observed in 82.4% (14 of 17). Median time on treatment was 27 months. Two of three patients responded to capmatinib plus OSI after progression on crizotinib plus OSI. Dual EGFR-MET inhibition was overall well tolerated. Two patients on crizotinib plus OSI and one pt on capmatinib plus OSI discontinued therapy due to pneumonitis. One pt discontinued crizotinib plus OSI due to gastrointestinal toxicity. Six patients were still on double TKI treatment. At disease progression to dual EGFR-MET inhibition, FISH and NGS on tumor and plasma were completed in six patients. Notable resistance mechanisms observed include acquired MET D1246H (n = 1), acquired EGFR C797S (n = 2), FGFR2 fusion (n = 1, concurrent with C797S), and EGFR G796S (n = 1, concurrent with C797S). Four patients lost MET amplification. Conclusions: Dual EGFR and MET inhibition yielded high clinical response rate after progression on OSI. Resistance mechanisms to EGFR-MET double TKI inhibition include MET secondary mutation, EGFR secondary mutation, or loss of MET amplification.

Although there is an established association between elevated triglyceride (eTG, ≥175 mg/dl) levels and adverse cardiovascular events, some studies have suggested that eTG levels may be linked to neutral or even improved clinical outcomes, particularly among patients with acute myocardial infarction. However, these studies had certain limitations, including small sample sizes, heterogeneous study populations, and inadequate statistical adjustments. To address these limitations, we conducted an analysis of 5347 patients with ST-segment elevation myocardial infarction (STEMI) between March 2003 and December 2020, using a prospective registry-based cohort from two large, regional STEMI centers. We used a triglyceride level of 175 mg/dl as the cutoff point for eTG levels. Of the study participants, 24.5% (n = 1312) had eTG levels. These patients were more likely to be younger, male, and have a higher number of cardiovascular risk factors compared to those with low TG levels. Despite these unfavorable cardiovascular risk profiles, patients with eTG levels had lower unadjusted risks of 1-year major adverse cardiac events (MACE) -a composite of myocardial infarction, stroke, and death- than those with low TG levels (8.8% vs. 11%, p = 0.034). However, after adjusting for certain clinical factors and lipid profile, eTG levels were not associated with a lower 1-year MACE (aHR: 1.10 (0.71–1.70), p = 0.7). In conclusion, a quarter of STEMI patients had eTG levels and these patients had comparable long-term cardiovascular outcomes compared to those with low TG levels after controlling for clinical factors and lipid profile.

Abstract Berkeley Madonna is a software program that provides an easy and intuitive environment for graphically building and numerically solving mathematical equations. Our users range from college undergraduates with little or no mathematical experience to academic researchers and professionals building and simulating sophisticated mathematical models that represent complex systems in the biological, chemical, and engineering fields. Here we briefly describe our recent advances including a new Java‐based user interface introduced in Version 9 and our transition from a 32‐ to 64‐bit architecture with the release of Version 10. We take the reader through an example tutorial that illustrates how to construct a mathematical model in Berkeley Madonna while highlighting some of the recent changes to the software. Specifically, we construct a standard pharmacokinetic model of the antifungal medication amphotericin B taken from the literature and discuss aspects related to model building, key numerical considerations, data fitting, and graphical visualization. We end by discussing planned functionality and features intended for future releases.

Background: Epidural analgesia (EA) is effective in patients undergoing minimal invasive repair of pectus excavatum (MIRPE) but is associated with major complications such as epidural hematomas. It is recommended to assess coagulation status in patients receiving anticoagulant therapy prior to EA, although no consensus exists in patients without a history of bleeding tendency or anticoagulant therapy. Thus, the aim of this paper was to assess 1) the prevalence of abnormal routine coagulation parameters, i.e., international normalized ratio (INR) and platelet count, and 2) the safety of EA in patients undergoing MIRPE. Methods: In this retrospective study, we identified 1,973 patients undergoing MIRPE at our center between 2001 and 2019. Complications related to EA were registered for all patients. Information on coagulation parameters was present in 929 patients. Patients with spontaneously elevated INR ≥1.5 were referred for assessment of coagulation factor VII in order to assess the cause of the elevated INR. Results: Of 929 patients with coagulation information available, 18 patients had spontaneously elevated INR ≥1.5 (1.9%). In patients with INR ≥1.5, 12 patients underwent further assessment of factor VII, with all patients having a slightly reduced factor VII close to the lower reference range. The majority of the 1,973 patients undergoing MIRPE received EA (99.6%) with very low complication rates (0.2%) and no incidence of epidural hematomas. Conclusion: In patients undergoing MIRPE, coagulation screening prior to EA should not be mandatory as it revealed no clinically relevant consequences. EA is safe with very low complication rates.

Abstract Knowledge of energy expenditure informs conservation managers for long term plans for endangered species health and habitat suitability. We measured field metabolic rate (FMR) of free-roaming giant pandas in large enclosures in a nature reserve using the doubly labeled water method. Giant pandas in zoo like enclosures had a similar FMR (14,182 kJ/day) to giant pandas in larger field enclosures (13,280 kJ/day). In winter, giant pandas raised their metabolic rates when living at − 2.4 °C (36,108 kJ/day) indicating that they were below their thermal neutral zone. The lower critical temperature for thermoregulation was about 8.0 °C and the upper critical temperature was about 28 °C. Giant panda FMRs were somewhat lower than active metabolic rates of sloth bears, lower than FMRs of grizzly bears and polar bears and 69 and 81% of predicted values based on a regression of FMR versus body mass of mammals. That is probably due to their lower levels of activity since other bears actively forage for food over a larger home range and pandas often sit in a patch of bamboo and eat bamboo for hours at a time. The low metabolic rates of giant pandas in summer, their inability to acquire fat stores to hibernate in winter, and their ability to raise their metabolic rate to thermoregulate in winter are energetic adaptations related to eating a diet composed almost exclusively of bamboo. Differences in FMR of giant pandas between our study and previous studies (one similar and one lower) appear to be due to differences in activity of the giant pandas in those studies.

ABSTRACT: OBJECTIVE: This phase I trial (NCT01912625) evaluated the safety and pharmacokinetics of definitive concurrent chemoradiotherapy (cCRT) and the radiosensitizer trametinib (MEK1/2 inhibitor) for KRAS-mutated nonmetastatic non-small cell lung cancer (NSCLC). METHODS: Patients received cCRT (carboplatin/paclitaxel and 60 Gy/30 fractions radiotherapy); oral trametinib (7 days/week) commenced on day 1 and completed on the final day of radiotherapy. Dose-finding of trametinib was done using the time-to-event continual reassessment method (TiTE-CRM); dose levels were 0.5mg (level -1), 1mg (initial, level 1), 1.5mg (level 2), and 2mg (level 3). Progression-free (PFS) and overall survival (OS) times were also recorded. RESULTS: Fifteen patients (stage III, variety of KRAS mutations) were treated, with 1/5/4/5 at dose levels -1/1/2/3, respectively. Five patients received dose reductions (n=2, levels 2 and 3; n=1, level 1). Twelve patients completed the full cCRT course. One patient (following 12d trametinib) was taken off protocol for an unrelated/unresolved grade 1 event and later experienced grade 5 sepsis/respiratory failure. There was one grade 4 retinal detachment; grade 3 events included skin rash (n=2) and ventricular dysfunction, pneumonitis, pain, fatigue, and diarrhea (n=1 each). The final dose selected by the TiTE-CRM of trametinib was 1.5 mg. Pharmacokinetic profiles were elucidated and extensively described. At median follow-up of 70 months, median PFS was 11 months and median OS was 38 months. CONCLUSIONS: The MTD for trametinib when combined with cCRT is 1.5 mg, with encouraging preliminary outcomes. This combination merits further study to combine with consolidation durvalumab in non-metastatic KRAS mutant NSCLC.

Abstract Endangered species are grouped into genetically discrete populations to direct conservation efforts. Mitochondrial control region (mtCR) haplotypes are used to elucidate deep divergences between populations, as compared to nuclear microsatellites that can detect recent structuring. When prior populations are unknown, it is useful to subject microsatellite data to clustering and/or ordination population inference. Olive ridley sea turtles (Lepidochelys olivacea) are the most abundant sea turtle, yet few studies have characterized olive ridley population structure. Recently, clustering results of olive ridleys in the Eastern Tropical Pacific Ocean suggested weak structuring (FST = 0.02) between Mexico and Central America. We analyzed mtCR haplotypes, new microsatellite genotypes from Costa Rica, and preexisting microsatellite genotypes from olive ridleys across the Eastern Tropical Pacific, to further explore population structuring in this region. We subjected inferred populations to multiple analyses to explore the mechanisms behind their structuring. We found 10 mtCR haplotypes from 60 turtles nesting at three sites in Costa Rica, but did not detect divergence between Costa Rican sites, or between Central America and Mexico. In Costa Rica, clustering suggested one population with no structuring, but ordination suggested four cryptic clusters with moderate structuring (FST = 0.08, p

Abstract Background Patients with mental illness are frequently treated in primary care, where Primary Care Providers (PCPs) report feeling ill-equipped to manage their care. Team-based models of care improve outcomes for patients with mental illness, but multiple barriers limit adoption. Barriers include practical issues and psychosocial factors associated with the reorganization of care. Practice facilitation can improve implementation, but does not directly address the psychosocial factors or gaps in PCP skills in managing mental illness. To address these gaps, we developed Relational Team Development (RELATED). Methods RELATED is an implementation strategy combining practice facilitation and psychology clinical supervision methodologies to improve implementation of team-based care. It includes PCP-level clinical coaching and a team-level practice change activity. We performed a preliminary assessment of RELATED with a convergent parallel mixed method study in 2 primary care clinics in an urban Federally Qualified Health Center in Southwest, USA, 2017-2018. Study participants included PCPs, clinic staff, and patient representatives. Clinic staff and patients were recruited for the practice change activity only. Primary outcomes were feasibility and acceptability. Feasibility was assessed as ease of recruitment and implementation. Acceptability was measured in surveys of PCPs and staff and focus groups. We conducted semi-structured focus groups with 3 participant groups in each clinic: PCPs; staff and patients; and leadership. Secondary outcomes were change in pre- post- intervention PCP self-efficacy in mental illness management and team-based care. We conducted qualitative observations to better understand clinic climate. Results We recruited 18 PCPs, 17 staff members, and 3 patient representatives. We ended recruitment early due to over recruitment. Both clinics developed and implemented practice change activities. The mean acceptability score was 3.7 (SD=0.3) on a 4-point Likert scale. PCPs had a statistically significant increase in their mental illness management self-efficacy [change = 0.9, p-value=

Background Most cell therapy trials failed to show an improvement in global left ventricular (LV) function measures after myocardial infarction (MI). Myocardial segments are heterogeneously impacted by MI. Global LV function indices are not able to detect the small treatment effects on segmental myocardial function which may have prognostic implications for cardiac events. We aimed to test the efficacy of allogeneic cardiosphere-derived cells (CDCs) for improving regional myocardial function and contractility.Methods In this exploratory analysis of a randomised clinical trial, 142 patients with post-MI with LVEF

In this study, we applied multiple reaction monitoring (MRM)-profiling to explore the relative ion intensity of lipid classes in plasma samples from sea turtles in order to profile lipids relevant to sea turtle physiology and investigate how dynamic ocean environments affect these profiles. We collected plasma samples from foraging green (Chelonia mydas, n = 28) and hawksbill (Eretmochelys imbricata, n = 16) turtles live captured in North Pacific Costa Rica in 2017. From these samples, we identified 623 MRMs belonging to 10 lipid classes (sphingomyelin, phosphatidylcholine, free fatty acid, cholesteryl ester, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, phosphatidylethanolamine, ceramide, and triacylglyceride) and one metabolite group (acyl-carnitine) present in sea turtle plasma. The relative ion intensities of most lipids (80%) were consistent between species, across seasons, and were not correlated to body size or estimated sex. Of the differences we observed, the most pronounced was the differences in relative ion intensity between species. We identified 123 lipids that had species-specific relative ion intensities. While some of this variability is likely due to green and hawksbill turtles consuming different food items, we found indications of a phylogenetic component as well. Of these, we identified 47 lipids that varied by season, most belonging to the structural phospholipid classes. Overall, more lipids (n = 39) had higher relative ion intensity in the upwelling (colder) season compared to the non-upwelling season (n = 8). Further, we found more variability in hawksbill turtles than green turtles. Here, we provide the framework in which to apply future lipid profiling in the assessment of health, physiology, and behavior in endangered sea turtles.

Background Protein supplementation has been suggested to augment endurance training adaptations by increasing mixed muscle and myofibrillar protein synthesis and lean body mass. However, a potential beneficial effect on mitochondrial adaptations is yet to be clarified. The aim of the present study was to investigate the effect of consuming whey protein hydrolysate before and whey protein hydrolysate plus carbohydrate (PRO-CHO) after each exercise session during a six-week training period compared to similarly timed intake of isocaloric CHO supplements on biomarkers of mitochondrial biogenesis, VO2max and performance in trained runners. Methods Twenty-four trained runners (VO2max 60.7 ± 3.7 ml O2 kg− 1 min1) completed a six-week block randomized controlled intervention period, consisting of progressive running training. Subjects were randomly assigned to either PRO-CHO or CHO and matched in pairs for gender, age, VO2max, training and performance status. The PRO-CHO group ingested a protein beverage (0.3 g kg− 1) before and protein-carbohydrate beverage (0.3 g protein kg− 1 and 1 g carbohydrate kg− 1) after each exercise session. The CHO group ingested an energy matched carbohydrate beverage. Resting muscle biopsies obtained pre and post intervention were analyzed for mitochondrial specific enzyme activity and mitochondrial protein content. Subjects completed a 6 K time trial (6 K TT) and a VO2max test pre, midway (only 6 K TT) and post intervention. Results Following six weeks of endurance training Cytochrome C (Cyt C) protein content was significantly higher in the PRO-CHO group compared to the CHO group (p

Sea level is expected to rise 44 to 74 cm by the year 2100, which may have critical, previously un-investigated implications for sea turtle nesting habitat on Bioko Island, Equatorial Guinea. This study investigates how nesting habitat will likely be lost and altered with various increases in sea level, using global sea level rise (SLR) predictions from the Intergovernmental Panel on Climate Change. Beach profiling datasets from Bioko's five southern nesting beaches were used in GIS to create models to estimate habitat loss with predicted increases in sea level by years 2046-2065 and 2081-2100. The models indicate that an average of 62% of Bioko's current nesting habitat could be lost by 2046-2065 and 87% by the years 2081-2100. Our results show that different study beaches showed different levels of vulnerability to increases in SLR. In addition, on two beaches erosion and tall vegetation berms have been documented, causing green turtles to nest uncharacteristically in front of the vegetation line. We also report that development plans are currently underway on the beach least susceptible to future increases in sea level, highlighting how anthropogenic encroachment combined with SLR can be particularly detrimental to nesting turtle populations. Identified habitat sensitivities to SLR will be used to inform the government of Equatorial Guinea to consider the vulnerability of their resident turtle populations and projected climate change implications when planning for future development. To our knowledge this is the first study to predict the impacts of SLR on a sea turtle nesting habitat in Africa.

Both heart failure with reduced (HFrEF) and preserved (HFpEF) ejection fraction are associated with abnormalities of the vasculature, including a resting vasoconstriction and a decrease in sensitivity to nitric oxide (NO) mediated vasodilation. Vascular tone is controlled by the expression and activation of both smooth muscle (SM) and nonmuscle (NM) myosin, and NO mediated vasodilation is regulated by the expression of the leucine zipper positive (LZ+) isoform of the myosin targeting subunit (MYPT1) of myosin light chain phosphatase (MLCP). This study was designed to determine the expression of these contractile proteins in humans with HFrEF and HFpEF vs normal controls. We isolated tertiary mesenteric vessels from remnant biospecimens of patients undergoing partial or total colectomy at Mayo Clinic Rochester from August 2017 to December 2018, and examined the expression of MYPT1 and the LZ + MYPT1 isoform with immunoblots, while 2D SDS-PAGE was used to resolve the phosphorylated and nonphosphorylated regulatory light chains of NM and SM myosin. Our data show that NM myosin expression, as a percentage of total myosin, was 12 ± 3% (controls, n = 6), 7 ± 5% (HFpEF, n = 4) and 37 ± 18% (HFrEF, n = 5, p < 0.05). Total MYPT1 expression was significantly reduced (p < 0.05) in both HFpEF (70 ± 11%) and HFrEF (48 ± 6%); and in HFrEF, LZ + MYPT1 was also depressed (62 ± 19%,

Understanding how regulators of inflammation affect nucleic acid sensing is important for targeting research against inflammatory diseases and conditions. Here, the authors identify Nrf2 as an important negative regulator of STING and suggest a link between metabolic reprogramming and antiviral cytosolic DNA sensing in human cells.

Purpose: High-load resistance exercise contributes to maintenance of muscle mass, muscle protein quality, and contractile function by stimulation of muscle protein synthesis (MPS), hypertrophy, and strength gains. However, high loading may not be feasible in several clinical populations. Low-load blood flow restricted resistance exercise (BFRRE) may provide an alternative approach. However, the long-term protein synthetic response to BFRRE is unknown and the myocellular adaptations to prolonged BFRRE are not well described.Methods: To investigate this, 34 healthy young subjects were randomized to 6 weeks of low-load BFRRE, HLRE, or non-exercise control (CON). Deuterium oxide (D2O) was orally administered throughout the intervention period. Muscle biopsies from m. vastus lateralis were collected before and after the 6-week intervention period to assess long-term myofibrillar MPS and RNA synthesis as well as muscle fiber-type-specific cross-sectional area (CSA), satellite cell content, and myonuclei content. Muscle biopsies were also collected in the immediate hours following single-bout exercise to assess signaling for muscle protein degradation. Isometric and dynamic quadriceps muscle strength was evaluated before and after the intervention.Results: Myofibrillar MPS was higher in BFRRE (1.34%/day, p

This study uses satellite telemetry to track post-nesting movements of endangered green turtles (Chelonia mydas) (n = 6) in the Gulf of Guinea. It identifies a migratory corridor linking breeding grounds of Atlantic green turtles nesting on Bioko Island, Equatorial Guinea, to foraging grounds in the coastal waters of Accra, Ghana. Track lengths of 20-198 days were analyzed, for a total of 536 movement days for the six turtles. Migratory pathways and foraging grounds were identified by applying a switching state space model to locational data, which provides daily position estimates to identify shifts between migrating and foraging behavior. Turtles exhibited a combination of coastal and oceanic migrations pathways that ranged from 957 km to 1,131 km. Of the six turtles, five completed their migration and maintained residency at the same foraging ground near the coastal waters of Accra, Ghana until transmission was lost. These five resident turtles inhabit heavily fished waters and are vulnerable to a variety of anthropogenic threats. The identification of these foraging grounds highlights the importance of these coastal waters for the protection of the endangered Atlantic green turtle.

Mangrove forests, one of the world's most endangered ecosystems, are also some of the most difficult to access. This is especially true along the Pacific coast of Costa Rica, where 99% of the country's mangroves occur. Unmanned Aerial Systems (UAS), or drones, have become a convenient tool for natural area assessment, and offer a solution to the problems of remote mangrove monitoring. This study is the first to use UAS to analyze the structure of a mangrove forests within Central America. Our goals were to (1) determine the forest structure of two estuaries in northwestern Costa Rica through traditional ground measurements, (2) assess the accuracy of UAS measurements of canopy height and percent coverage and (3) determine whether the normalized difference vegetation index (NDVI) could discriminate between the most abundant mangrove species. We flew a UAS equipped with a single NDVI sensor during the peak wet (Sept-Nov) and dry (Jan-Feb) seasons. The structure and species composition of the estuaries showed a possible transition between the wet mangroves of southern Costa Rica and the drier northern mangroves. UAS-derived measurements at 100 cm/pixel resolution of percent canopy coverage and maximum and mean canopy height were not statistically different from ground measurements (p > 0.05). However, there were differences in mean canopy height at 10 cm/pixel resolution (p = 0.043), indicating diminished returns in accuracy as resolution becomes extremely fine. Mean NDVI values of Avicennia germinans (most abundant species) changed significantly between seasons (p < 0.001). Mean NDVI of Rhizophora racemosa (second most abundant species) was significantly different from A. germinans and dry forest dominant plots during the dry season (p < 0.001), demonstrating NDVI's capability of discriminating mangrove species. This study provides the first structural assessment of the studied estuaries and a framework for future studies of mangroves using UAS.

The survival rate of penetrating cardiac trauma is dismal, with only a few patients reaching the hospital with any signs of life. Short transport time and close proximity to the trauma center are positive factors for survival. We report the successful case of a 21-year-old male with penetrating cardiac injury and tension-pneumothorax with long distance to a trauma facility. The patient was stabbed twice in the anterior left side of the thorax. The emergency services found the patient with suspicion of left tension-pneumothorax. Urgent left mini-thoracotomy was established resulting in spontaneous respiration and clinical improvement. Due to rapid clinical deterioration and clinical suspicion of pericardial tamponade, patient was transported to the local regional hospital only minutes away. Echocardiography confirmed tamponade, and urgent ultrasound-guided pericardiocentesis was performed. During the transport blood was intermittently drained from the pericardial sack until arrival at the trauma center where a penetrating injury to the left ventricle was repaired during urgent cardiac surgery. The patient was discharged 8 days after the incident. Conclusion. Well organized emergency medical transport systems increase the chance of survival in penetrating cardiac injuries. Urgent pericardiocentesis with continuous drainage can help stabilize a patient until arrival at trauma facility.

Purpose: It is well established that high-load resistance exercise (HLRE) can stimulate myofibrillar accretion. Additionally, recent studies suggest that HLRE can also stimulate mitochondrial biogenesis and respiratory function. However, in several clinical situations, the use of resistance exercise with high loading may not constitute a viable approach. Low-load blood flow restricted resistance exercise (BFRRE) has emerged as a time-effective low-load alternative to stimulate myofibrillar accretion. It is unknown if BFRRE can also stimulate mitochondrial biogenesis and respiratory function. If so, BFRRE could provide a feasible strategy to stimulate muscle metabolic health.Methods: To study this, 34 healthy previously untrained individuals (24 ± 3 years) participated in BFRRE, HLRE, or non-exercise control intervention (CON) 3 times per week for 6 weeks. Skeletal muscle biopsies were collected; (1) before and after the 6-week intervention period to assess mitochondrial biogenesis and respiratory function and; (2) during recovery from single-bout exercise to assess myocellular signaling events involved in transcriptional regulation of mitochondrial biogenesis. During the 6-week intervention period, deuterium oxide (D2O) was continuously administered to the participants to label newly synthesized skeletal muscle mitochondrial proteins. Mitochondrial respiratory function was assessed in permeabilized muscle fibers with high-resolution respirometry. Mitochondrial content was assessed with a citrate synthase activity assay. Myocellular signaling was assessed with immunoblotting.Results: Mitochondrial protein synthesis rate was higher with BFRRE (1.19%/day) and HLRE (1.15%/day) compared to CON (0.92%/day) (P < 0.05) but similar between exercise groups. Mitochondrial respiratory function increased to similar degree with both exercise regimens and did not change with CON. For instance, coupled respiration supported by convergent electron flow from complex I and II increased 38% with BFRRE and 24% with HLRE (P < 0.01). Training did not alter citrate synthase activity compared to CON. BFRRE and HLRE elicited similar myocellular signaling responses.Conclusion: These results support recent findings that resistance exercise can stimulate mitochondrial biogenesis and respiratory function to support healthy skeletal muscle and whole-body metabolism. Intriquingly, BFRRE produces similar mitochondrial adaptations at a markedly lower load, which entail great clinical perspective for populations in whom exercise with high loading is untenable.

We report a new strategy for generating a continuum of response profiles from a single luminescence-based sensor element by using phase-resolved detection. This strategy yields reliable responses that depend in a predictable manner on changes in the luminescent reporter lifetime in the presence of the target analyte, the excitation modulation frequency, and the detector (lock-in amplifier) phase angle. In the traditional steady-state mode, the sensor that we evaluate exhibits a linear, positive going response to changes in the target analyte concentration. Under phase-resolved conditions the analyte-dependent response profiles: (i) can become highly non-linear; (ii) yield negative going responses; (iii) can be biphasic; and (iv) can exhibit super sensitivity (e.g., sensitivities up to 300 fold greater in comparison to steady-state conditions).

There are two primary components that produce pulmonary arterial hypertension (PAH); aberrant structural changes (smooth muscle cell proliferation, smooth muscle cell hypertrophy, and the deposition of matrix proteins within the media of pulmonary arterial vessels), and excess vasoconstriction. However, in PAH, the target and aim of all current therapeutic agents is to reduce the contractility of the pulmonary vasculature; prostaglandins, phosphodiesterase inhibitors, guanylate cyclase stimulators, endothelin antagonists, NO inhalation and Rho kinase inhibitors all influence signaling pathways in the pulmonary vascular smooth muscle to decrease vasoconstriction, and hence, pulmonary vascular resistance (PVR). This review will therefore primarily focus on discussing the signaling pathways regulating contractility in pulmonary vascular smooth muscle, the mechanism for current treatments, as well as highlighting potential targets for the development of novel therapies.

Thermal tolerances are affected by the range of temperatures that species encounter in their habitat. Daniel Janzen hypothesized in his "Why mountain passes are higher in the tropics" that temperature gradients were effective barriers to animal movements where climatic uniformity was high. Sea turtles bury their eggs providing some thermal stability that varies with depth. We assessed the relationship between thermal uniformity and thermal tolerance in nests of three species of sea turtles. We considered that barriers were "high" when small thermal changes had comparatively large effects and "low" when the effects were small. Mean temperature was lower and fluctuated less in species that dig deeper nests. Thermal barriers were comparatively "higher" in leatherback turtle (Dermochelys coriacea) nests, which were the deepest, as embryo mortality increased at lower "high" temperatures than in olive ridley (Lepidochelys olivacea) and green turtle (Chelonia mydas) nests. Sea turtles have temperature-dependent sex determination (TSD) and embryo mortality increased as temperature approached the upper end of the transitional range of temperatures (TRT) that produces both sexes (temperature producing 100% female offspring) in leatherback and olive ridley turtles. As thermal barriers are "higher" in some species than in others, the effects of climate warming on embryo mortality is likely to vary among sea turtles. Population resilience to climate warming may also depend on the balance between temperatures that produce female offspring and those that reduce embryo survival.

The gut microbiome of herbivorous animals consists of organisms that efficiently digest the structural carbohydrates of ingested plant material. Green turtles (Chelonia mydas) provide an interesting model of change in these microbial communities because they undergo a pronounced shift from a surface-pelagic distribution and omnivorous diet to a neritic distribution and herbivorous diet. As an alternative to direct sampling of the gut, we investigated the cloacal microbiomes of juvenile green turtles before and after recruitment to neritic waters to observe any changes in their microbial community structure. Cloacal swabs were taken from individual turtles for analysis of the 16S rRNA gene sequences using Illumina sequencing. One fecal sample was also obtained, allowing for a preliminary comparison with the bacterial community of the cloaca. We found significant variation in the juvenile green turtle bacterial communities between pelagic and neritic habitats, suggesting that environmental and dietary factors support different bacterial communities in green turtles from these habitats. This is the first study to characterize the cloacal microbiome of green turtles in the context of their ontogenetic shifts, which could provide valuable insight into the origins of their gut bacteria and how the microbial community supports their shift to herbivory.

The red panda (Ailurus fulgens) has a similar diet, primarily bamboo, and shares the same habitat as the giant panda, Ailuropoda melanoleuca. There are considerable efforts underway to understand the ecology of the red panda and to increase its populations in natural reserves. Yet it is difficult to design an effective strategy for red panda reintroduction if we do not understand its basic biology. Here we report the resting metabolic rate of the red panda and find that it is higher than previously measured on animals from a zoo. The resting metabolic rate was 0.290 ml/g/h (range 0.204-0.342) in summer and 0.361 ml/g/h in winter (range 0.331-0.406), with a statistically significant difference due to season and test temperature. Temperatures in summer were probably within the thermal neutral zone for metabolism but winter temperatures were below the thermal neutral zone. There was no difference in metabolic rate between male and female red pandas and no difference due to mass. Our values for metabolic rate were much higher than those measured by McNab for 2 red pandas from a zoo. The larger sample size (17), more natural conditions at the Panda Base and improved accuracy of the metabolic instruments provided more accurate metabolism measurements. Contrary to our expectations based on their low quality bamboo diet, the metabolic rates of red pandas were similar to mammals of the same size. Based on their metabolic rates red pandas would not be limited by their food supply in natural reserves.

Two-dimensional (2D) materials are being used widely for chemical sensing applications due to their large surface-to-volume ratio and photoluminescence (PL) emission and emission exciton band tunability. To better understand how the analyte affects the PL response for a model 2D platform, we used atomic force microscopy (AFM) and co-localized photoluminescence (PL) and Raman mapping to characterize tungsten disulfide (WS2) flakes on template-stripped gold (TSG) under acetone challenge. We determined the PL-based response from single- and few-layer WS2 arises from three excitons (neutral, A0; biexciton, AA; and the trion, A−). The A0 exciton PL emission is the most strongly quenched by acetone whereas the A− PL emission exhibits an enhancement. We find the PL behavior is also WS2 layer number dependent.

The macro-epibiotic communities of sea turtles have been subject to growing interest in recent years, yet their micro-epibiotic counterparts are almost entirely unknown. Here, we provide the first evidence that diatoms are epibionts for all seven extant species of sea turtle. Using Scanning Electron Microscopy, we inspected superficial carapace or skin samples from a single representative of each turtle species. We distinguished 18 diatom taxa from these seven individuals, with each sea turtle species hosting at least two diatom taxa. We recommend that future research is undertaken to confirm whether diatom communities vary between sea turtle species and whether these diatom taxa are facultative or obligate commensals.

Increasing sand temperatures resulting from climate change may negatively impact sea turtle nests by altering sex ratios and decreasing reproductive output. We analyzed the effect of nest shading and watering on sand temperatures as climate mitigation strategies in a beach hatchery at Playa Grande, Costa Rica. We set up plots and placed thermocouples at depths of 45 cm and 75 cm. Half of the plots were shaded and half were exposed to the sun. Within these exposure treatments, we applied three watering treatments over one month, replicating local climatic conditions experienced in this area. We also examined gravimetric water content of sand by collecting sand samples the day before watering began, the day after watering was complete, and one month after completion. Shading had the largest impact on sand temperature, followed by watering and depth. All watering treatments lowered sand temperature, but the effect varied with depth. Temperatures in plots that received water returned to control levels within 10 days after watering stopped. Water content increased at both depths in the two highest water treatments, and 30 days after the end of water application remained higher than plots with low water. While the impacts of watering on sand temperature dissipate rapidly after the end of application, the impacts on water content are much more lasting. Although less effective at lowering sand temperatures than shading, watering may benefit sea turtle clutches by offsetting negative impacts of low levels of rain in particularly dry areas. Prior to implementing such strategies, the natural conditions at the location of interest (e.g. clutch depth, environmental conditions, and beach characteristics) and natural hatchling sex ratios should be taken into consideration. These results provide insight into the effectiveness of nest shading and watering as climate mitigation techniques and illustrate important points of consideration in the crafting of such strategies.

Phosphodiesterase-5 (PDE5) is highly expressed in the pulmonary vasculature, but its expression in the myocardium is controversial. Cyclic guanosine monophosphate (cGMP) activates protein kinase G (PKG), which has been hypothesized to blunt cardiac hypertrophy and negative remodeling in heart failure. Although PDE5 has been suggested to play a significant role in the breakdown of cGMP in cardiomyocytes and hence PKG regulation in the myocardium, the RELAX trial, which tested effect of PDE5 inhibition on exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF) failed to show a beneficial effect. These results highlight the controversy regarding the role and expression of PDE5 in the healthy and failing heart. This study used one- and two-dimensional electrophoresis and Western blotting to examine PDE5 expression in mouse (before and after trans-aortic constriction), dog (control and HFpEF) as well as human (healthy and failing) heart. We were unable to detect PDE5 in any cardiac tissue lysate, whereas PDE5 was present in the murine and bovine lung samples used as positive controls. These results indicate that if PDE5 is expressed in cardiac tissue, it is present in very low quantities, as PDE5 was not detected in either humans or any model of heart failure examined. Therefore in cardiac muscle, it is unlikely that PDE5 is involved the regulation of cGMP-PKG signaling, and hence PDE5 does not represent a suitable drug target for the treatment of cardiac hypertrophy. These results highlight the importance of rigorous investigation prior to clinical trial design.

While neurohumoral antagonists improve outcomes in heart failure (HF), cardiac remodeling and dysfunction progress and outcomes remain poor. Therapies superior or additive to standard HF therapy are needed. Pharmacologic mTOR inhibition by rapamycin attenuated adverse cardiac remodeling and dysfunction in experimental heart failure (HF). However, these studies used rapamycin doses that produced blood drug levels targeted for primary immunosuppression in human transplantation and therefore the immunosuppressive effects may limit clinical translation. Further, the relative or incremental effect of rapamycin combined with standard HF therapies targeting upstream regulators of cardiac remodeling (neurohumoral antagonists) has not been defined. Our objectives were to determine if anti-remodeling effects of rapamycin were preserved at lower doses and whether rapamycin effects were similar or additive to a standard HF therapy (angiotensin receptor blocker (losartan)). Experimental murine HF was produced by transverse aortic constriction (TAC). At three weeks post-TAC, male mice with established HF were treated with placebo, rapamycin at a dose producing immunosuppressive drug levels (target dose), low dose (50% target dose) rapamycin, losartan or rapamycin + losartan for six weeks. Cardiac structure and function (echocardiography, catheterization, pathology, hypertrophic and fibrotic gene expression profiles) were assessed. Downstream mTOR signaling pathways regulating protein synthesis (S6K1 and S6) and autophagy (LC3B-II) were characterized. TAC-HF mice displayed eccentric hypertrophy, systolic dysfunction and pulmonary congestion. These perturbations were attenuated to a similar degree by oral rapamycin doses achieving target (13.3±2.1 ng/dL) or low (6.7±2.5 ng/dL) blood levels. Rapamycin treatment decreased mTOR mediated regulators of protein synthesis and increased mTOR mediated regulators of autophagy. Losartan monotherapy did not attenuate remodeling, whereas Losartan added to rapamycin provided no incremental benefit over rapamycin alone. These data lend support to investigation of low dose rapamycin as a novel therapy in human HF.

Egg-burying reptiles need relatively stable temperature and humidity in the substrate surrounding their eggs for successful development and hatchling emergence. Here we show that egg and hatchling mortality of leatherback turtles (Dermochelys coriacea) in northwest Costa Rica were affected by climatic variability (precipitation and air temperature) driven by the El Niño Southern Oscillation (ENSO). Drier and warmer conditions associated with El Niño increased egg and hatchling mortality. The fourth assessment report of the Intergovernmental Panel on Climate Change (IPCC) projects a warming and drying in Central America and other regions of the World, under the SRES A2 development scenario. Using projections from an ensemble of global climate models contributed to the IPCC report, we project that egg and hatchling survival will rapidly decline in the region over the next 100 years by ∼50-60%, due to warming and drying in northwestern Costa Rica, threatening the survival of leatherback turtles. Warming and drying trends may also threaten the survival of sea turtles in other areas affected by similar climate changes.

Foraging success for pelagic vertebrates may be revealed by horizontal and vertical movement patterns. We show markedly different patterns for leatherback turtles in the North Atlantic versus Eastern Pacific, which feed on gelatinous zooplankton that are only occasionally found in high densities. In the Atlantic, travel speed was characterized by two modes, indicative of high foraging success at low speeds (

Leatherback turtles have an average global hatching success rate of ~50%, lower than other marine turtle species. Embryonic death has been linked to environmental factors such as precipitation and temperature, although, there is still a lot of variability that remains to be explained. We examined how nesting season, the time of nesting each season, the relative position of each clutch laid by each female each season, maternal identity and associated factors such as reproductive experience of the female (new nester versus remigrant) and period of egg retention between clutches (interclutch interval) affected hatching success and stage of embryonic death in failed eggs of leatherback turtles nesting at Playa Grande, Costa Rica. Data were collected during five nesting seasons from 2004/05 to 2008/09. Mean hatching success was 50.4%. Nesting season significantly influenced hatching success in addition to early and late stage embryonic death. Neither clutch position nor nesting time during the season had a significant affect on hatching success or the stage of embryonic death. Some leatherback females consistently produced nests with higher hatching success rates than others. Remigrant females arrived earlier to nest, produced more clutches and had higher rates of hatching success than new nesters. Reproductive experience did not affect stage of death or the duration of the interclutch interval. The length of interclutch interval had a significant affect on the proportion of eggs that failed in each clutch and the developmental stage they died at. Intrinsic factors such as maternal identity are playing a role in affecting embryonic death in the leatherback turtle.

Do pesticide residues persist on bush tomatoes? Apparently not — or at least not much, according to a new study. When fruit was treated directly, then washed and brushed during normal postharvest handling, most — if not all — chemical residues were reduced by 50 to 95%. Extensive sampling at commercial packing facilities showed no detectable residues.

Heart failure is associated with impairment in nitric oxide (NO) mediated vasodilatation, which has been demonstrated to result from a reduction in the relative expression of the leucine zipper positive (LZ+) isoform of the myosin targeting subunit (MYPT1) of myosin light chain phosphatase. Further, captopril preserves normal LZ+ MYPT1 expression, the sensitivity to cGMP-mediated vasodilatation and modulates the expression of genes in the p42/44 MAPK and p38 MAPK signaling cascades. This study tests whether angiotensin receptor blockade (ARB) with losartan decreases p42/44 MAPK or p38 MAPK signaling and preserves LZ+ MYPT1 expression in a rat infarct model of heart failure. In aortic smooth muscle, p42/44 MAPK activation increases and LZ+ MYPT1 expression falls after LAD ligation. Losartan treatment decreases the activation of p42/44 MAPK to the uninfarcted control level and preserves normal LZ+ MYPT1 expression. The expression and activation of p38 MAPK, however, is low and does not change following LAD ligation or with losartan therapy. These data suggest that either reducing or blocking the effects of circulating angiotensin II, both decreases the activation of the p42/44 MAPK signaling cascade and preserves LZ+ MYPT1 expression. Thus, the ability of ACE-inhibitors and ARBs to modulate the vascular phenotype, to preserve normal flow mediated vasodilatation may explain the beneficial effects of these drugs compared to other forms of afterload reduction in the treatment of heart failure.

Increasing efforts and financial resources are being invested in early cancer detection research. Blood assays detecting tumor biomarkers promise noninvasive and financially reasonable screening for early cancer with high potential of positive impact on patients' survival and quality of life. For novel tumor biomarkers, the actual tumor detection limits are usually unknown and there have been no studies exploring the tumor burden detection limits of blood tumor biomarkers using mathematical models. Therefore, the purpose of this study was to develop a mathematical model relating blood biomarker levels to tumor burden.Using a linear one-compartment model, the steady state between tumor biomarker secretion into and removal out of the intravascular space was calculated. Two conditions were assumed: (1) the compartment (plasma) is well-mixed and kinetically homogenous; (2) the tumor biomarker consists of a protein that is secreted by tumor cells into the extracellular fluid compartment, and a certain percentage of the secreted protein enters the intravascular space at a continuous rate. The model was applied to two pathophysiologic conditions: tumor biomarker is secreted (1) exclusively by the tumor cells or (2) by both tumor cells and healthy normal cells. To test the model, a sensitivity analysis was performed assuming variable conditions of the model parameters. The model parameters were primed on the basis of literature data for two established and well-studied tumor biomarkers (CA125 and prostate-specific antigen [PSA]). Assuming biomarker secretion by tumor cells only and 10% of the secreted tumor biomarker reaching the plasma, the calculated minimally detectable tumor sizes ranged between 0.11 mm(3) and 3,610.14 mm(3) for CA125 and between 0.21 mm(3) and 131.51 mm(3) for PSA. When biomarker secretion by healthy cells and tumor cells was assumed, the calculated tumor sizes leading to positive test results ranged between 116.7 mm(3) and 1.52 x 10(6) mm(3) for CA125 and between 27 mm(3) and 3.45 x 10(5) mm(3) for PSA. One of the limitations of the study is the absence of quantitative data available in the literature on the secreted tumor biomarker amount per cancer cell in intact whole body animal tumor models or in cancer patients. Additionally, the fraction of secreted tumor biomarkers actually reaching the plasma is unknown. Therefore, we used data from published cell culture experiments to estimate tumor cell biomarker secretion rates and assumed a wide range of secretion rates to account for their potential changes due to field effects of the tumor environment.This study introduced a linear one-compartment mathematical model that allows estimation of minimal detectable tumor sizes based on blood tumor biomarker assays. Assuming physiological data on CA125 and PSA from the literature, the model predicted detection limits of tumors that were in qualitative agreement with the actual clinical performance of both biomarkers. The model may be helpful in future estimation of minimal detectable tumor sizes for novel proteomic biomarker assays if sufficient physiologic data for the biomarker are available. The model may address the potential and limitations of tumor biomarkers, help prioritize biomarkers, and guide investments into early cancer detection research efforts.

Effective transboundary conservation of highly migratory marine animals requires international management cooperation as well as clear scientific information about habitat use by these species. Populations of leatherback turtles (Dermochelys coriacea) in the eastern Pacific have declined by >90% during the past two decades, primarily due to unsustainable egg harvest and fisheries bycatch mortality. While research and conservation efforts on nesting beaches are ongoing, relatively little is known about this population of leatherbacks' oceanic habitat use and migration pathways. We present the largest multi-year (2004-2005, 2005-2006, and 2007) satellite tracking dataset (12,095 cumulative satellite tracking days) collected for leatherback turtles. Forty-six females were electronically tagged during three field seasons at Playa Grande, Costa Rica, the largest extant nesting colony in the eastern Pacific. After completing nesting, the turtles headed southward, traversing the dynamic equatorial currents with rapid, directed movements. In contrast to the highly varied dispersal patterns seen in many other sea turtle populations, leatherbacks from Playa Grande traveled within a persistent migration corridor from Costa Rica, past the equator, and into the South Pacific Gyre, a vast, low-energy, low-productivity region. We describe the predictable effects of ocean currents on a leatherback migration corridor and characterize long-distance movements by the turtles in the eastern South Pacific. These data from high seas habitats will also elucidate potential areas for mitigating fisheries bycatch interactions. These findings directly inform existing multinational conservation frameworks and provide immediate regions in the migration corridor where conservation can be implemented. We identify high seas locations for focusing future conservation efforts within the leatherback dispersal zone in the South Pacific Gyre.