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The humphead wrasse Cheilinus undulatus is an iconic, ecologically important and Endangered fish species associated with coral reefs in the Indo-Pacific region. Due to its large size and complex life history characteristics, it is vulnerable to overfishing and has undergone substantial population declines in parts of its range. Knowledge of the species’ movement ecology is currently limited to only 2 previous studies, and very little is known about populations in the western Indian Ocean. The present study aimed to use passive acoustic telemetry to investigate the importance of a remote coral reef to a population of humphead wrasse in the Republic of Seychelles, and subsequently assess the efficacy of a proposed marine protected area at this location for protection of the species. Tagged fish (n = 20) exhibited persistent (>500 d) site fidelity, with low dispersal distances (mean ± SD: 6.44 ± 4.0 km) and restricted core activity spaces (50% Brownian bridge kernel utilization density: 0.91 ± 0.61 km2). Additionally, the study site was home to a group of large (total length 97.9 ± 20.6 cm) and currently unexploited humphead wrasse that showed long-term predictable site fidelity and thus could be vulnerable to over-exploitation. The establishment of a proposed no-take marine protected area at the study site would encompass the core home range area of all tagged humphead wrasse and could effectively conserve this stronghold of Endangered fish to ensure the persistence of the species in Seychelles waters.

Monkeypox (Mpox) has emerged as a global threat since 2022. We reported 14 cases of Mpox in 10 people with HIV (PWH) and 4 people without HIV (PWoH), of whom 64.3% had sexually transmitted co-infections. Severe complications of Mpox and prolonged viral shedding might occur in both PWH and PWoH., (Copyright © 2024. Published by Elsevier B.V.)

Background: The KCNQ1+KCNE1 (I Ks ) potassium channel plays a crucial role in cardiac adaptation to stress, in which β-adrenergic stimulation phosphorylates the I Ks channel through the cyclic adenosine monophosphate (cAMP)/PKA (protein kinase A) pathway. Phosphorylation increases the channel current and accelerates repolarization to adapt to an increased heart rate. Variants in KCNQ1 can cause long-QT syndrome type 1 (LQT1), and those with defective cAMP effects predispose patients to the highest risk of cardiac arrest and sudden death. However, the molecular connection between I Ks channel phosphorylation and channel function, as well as why high-risk LQT1 mutations lose cAMP sensitivity, remain unclear., Methods: Regular patch clamp and voltage clamp fluorometry techniques were utilized to record pore opening and voltage sensor movement of wild-type and mutant KCNQ1/I Ks channels. The clinical phenotypic penetrance of each LQT1 mutation was analyzed as a metric for assessing their clinical risk. The patient-specific-induced pluripotent stem-cell model was used to test mechanistic findings in physiological conditions., Results: By systematically elucidating mechanisms of a series of LQT1 variants that lack cAMP sensitivity, we identified molecular determinants of I Ks channel regulation by phosphorylation. These key residues are distributed across the N-terminus of KCNQ1 extending to the central pore region of I Ks . We refer to this pattern as the I Ks channel PKA phosphorylation axis. Next, by examining LQT1 variants from clinical databases containing 10 579 LQT1 carriers, we found that the distribution of the most high-penetrance LQT1 variants extends across the I Ks channel PKA phosphorylation axis, demonstrating its clinical relevance. Furthermore, we found that a small molecule, ML277, which binds at the center of the phosphorylation axis, rescues the defective cAMP effects of multiple high-risk LQT1 variants. This finding was then tested in high-risk patient-specific induced pluripotent stem cell-derived cardiomyocytes, where ML277 remarkably alleviates the beating abnormalities., Conclusions: Our findings not only elucidate the molecular mechanism of PKA-dependent I Ks channel phosphorylation but also provide an effective antiarrhythmic strategy for patients with high-risk LQT1 variants., Competing Interests: None.

Cantú syndrome (CS), a multisystem disease with a complex cardiovascular phenotype, is caused by gain-of-function (GoF) variants in the Kir6.1/SUR2 subunits of ATP-sensitive potassium (KATP) channels and is characterized by low systemic vascular resistance, as well as tortuous, dilated, vessels, and decreased pulse-wave velocity. Thus, CS vascular dysfunction is multifactorial, with both hypomyotonic and hyperelastic components. To dissect whether such complexities arise cell autonomously within vascular smooth muscle cells (VSMCs) or as secondary responses to the pathophysiological milieu, we assessed electrical properties and gene expression in human induced pluripotent stem cell-derived VSMCs (hiPSC-VSMCs), differentiated from control and CS patient-derived hiPSCs, and in native mouse control and CS VSMCs. Whole-cell voltage clamp of isolated aortic and mesenteric arterial VSMCs isolated from wild-type (WT) and Kir6.1[V65M] (CS) mice revealed no clear differences in voltage-gated K+ (Kv) or Ca2+ currents. Kv and Ca2+ currents were also not different between validated hiPSC-VSMCs differentiated from control and CS patient-derived hiPSCs. While pinacidil-sensitive KATP currents in control hiPSC-VSMCs were similar to those in WT mouse VSMCs, they were considerably larger in CS hiPSC-VSMCs. Under current-clamp conditions, CS hiPSC-VSMCs were also hyperpolarized, consistent with increased basal K conductance and providing an explanation for decreased tone and decreased vascular resistance in CS. Increased compliance was observed in isolated CS mouse aortae and was associated with increased elastin mRNA expression. This was consistent with higher levels of elastin mRNA in CS hiPSC-VSMCs and suggesting that the hyperelastic component of CS vasculopathy is a cell-autonomous consequence of vascular KATP GoF. The results show that hiPSC-VSMCs reiterate expression of the same major ion currents as primary VSMCs, validating the use of these cells to study vascular disease. Results in hiPSC-VSMCs derived from CS patient cells suggest that both the hypomyotonic and hyperelastic components of CS vasculopathy are cell-autonomous phenomena driven by KATP overactivity within VSMCs ., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Physiological Society.)

Humans alter ecosystems through both consumptive and non-consumptive effects. Consumptive effects occur through hunting, fishing and collecting, while non-consumptive effects occur due to the responses of wildlife to human presence. While marine conservation efforts have focused on reducing consumptive effects, managing human presence is also necessary to maintain and restore healthy ecosystems. Area closures and the tourism freeze related to the COVID-19 pandemic provided a unique natural experiment to measure the effects of decreased tourism on fish behavior in a high use no-take marine protected area (MPA) in Hawai`i. We found that when tourism shut down due to COVID restrictions in 2020, fish biomass increased and predatory species increased usage of shallow habitats, where tourists typically concentrate. When tourism resumed, fish biomass and habitat use returned to pre-pandemic levels. These displacement effects change fish community composition and biomass, which could affect key processes such as spawning, foraging and resting, and have knock-on effects that compromise ecosystem function and resilience. Managing non-consumptive uses, especially in heavily-visited MPAs, should be considered for sustainability of these ecosystems., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Weng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Doctors, nowadays, primarily use auditory-perceptual evaluation, such as the grade, roughness, breathiness, asthenia, and strain scale, to evaluate voice quality and determine the treatment. However, the results predicted by individual physicians often differ, because of subjective perceptions, and diagnosis time interval, if the patient's symptoms are hard to judge. Therefore, an accurate computerized pathological voice quality assessment system will improve the quality of assessment., Method: This study proposes a self_attention-based system, with a deep learning technology, named self_attention-based bidirectional long-short term memory (SA BiLSTM). Different pitches [low, normal, high], and vowels [/a/, /i/, /u/], were added into the proposed model, to make it learn how professional doctors evaluate the grade, roughness, breathiness, asthenia, and strain scale, in a high dimension view., Results: The experimental results showed that the proposed system provided higher performance than the baseline system. More specifically, the macro average of the F1 score, presented as decimal, was used to compare the accuracy of classification. The (G, R, and B) of the proposed system were (0.768±0.011, 0.820±0.009, and 0.815±0.009), which is higher than the baseline systems: deep neural network (0.395±0.010, 0.312±0.019, 0.321±0.014) and convolution neural network (0.421±0.052, 0.306±0.043, 0.3250±0.032) respectively., Conclusions: The proposed system, with SA BiLSTM, pitches, and vowels, provides a more accurate way to evaluate the voice. This will be helpful for clinical voice evaluations and will improve patients' benefits from voice therapy., (Copyright © 2023 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Atrial fibrillation (AF) is the most common arrhythmia in the United States, affecting approximately 1 in 10 adults, and its prevalence is expected to rise as the population ages. Treatment options for AF are limited; moreover, the development of new treatments is hindered by limited (1) knowledge regarding human atrial electrophysiological endpoints (e.g., conduction velocity [CV]) and (2) accurate experimental models. Here, we measured the CV and refractory period, and subsequently calculated the conduction wavelength, in vivo (four subjects with AF and four controls), and ex vivo (atrial slices from human hearts). Then, we created an in vitro model of human atrial conduction using induced pluripotent stem (iPS) cells. This model consisted of iPS-derived human atrial cardiomyocytes plated onto a micropatterned linear 1D spiral design of Matrigel. The CV (34-41 cm/s) of the in vitro model was nearly five times faster than 2D controls (7-9 cm/s) and similar to in vivo (40-64 cm/s) and ex vivo (28-51 cm/s) measurements. Our iPS-derived in vitro model recapitulates key features of in vivo atrial conduction and may be a useful methodology to enhance our understanding of AF and model patient-specific disease., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements.

Advances in the design and synthesis of nanomaterials with desired biophysicochemical properties can be harnessed to develop non-invasive neuromodulation technologies. Here, the reversible modulation of the electrical activity of neurons and cardiomyocytes is demonstrated using polydopamine (PDA) nanoparticles as photothermal nanotransducers. In addition to their broad light absorption and excellent photothermal activity, PDA nanoparticles are highly biocompatible and biodegradable, making them excellent candidates for both in vitro and in vivo applications. The modulation of the activity (i.e., spike rate of the neurons and beating rate of cardiomyocytes) of excitable cells can be finely controlled by varying the excitation power density and irradiation duration. Under optimal conditions, reversible suppression (≈100%) of neural activity and reversible enhancement (two-fold) in the beating rate of cardiomyocytes is demonstrated. To improve the ease of interfacing of photothermal transducers with these excitable cells and enable spatial localization of the photothermal stimulus, a collagen/PDA nanoparticle foam is realized, which can be used as an "add-on patch" for photothermal stimulation. The non-genetic optical neuromodulation approach using biocompatible and biodegradable nanoparticles represents a minimally invasive method for controlling the activity of excitable cells with potential applications in nano-neuroscience and engineering., (© 2021 Wiley-VCH GmbH.)

Artificial reefs act as high-rugosity habitats and are often deployed to enhance fishing; however, the effects of man-made features on fish communities can be unpredictable and are poorly understood in deeper waters. In this study, we used a submersible to describe a deep-water artificial reef complex (93-245 m) off of Ewa Beach, Oahu, Hawaii, USA, and evaluated possible conservation and/or fisheries-related contributions. Sixty-eight species were recorded, with larger features supporting greater diversity of species. Species composition changed strongly with depth and a faunal break was detected from 113-137 m. While the features supported diverse fish communities, they were not similar to those on natural substrates, and were numerically dominated by only two species, Lutjanis kasmira and Chromis verater. Depth-generalist and endemic species were present at levels comparable to natural substrates, but were less abundant and species-rich than at biogenic Leptoseris reefs at similar depths. While the non-native L. kasmira was highly abundant, its presence and abundance were not associated with discernable changes in the fish community, and was not present deeper than 120 m. Finally, five species of commercially- and recreationally-important 'Deep 7' fisheries species were also observed, but the artificial reef complex was mostly too shallow to provide meaningful benefits., Competing Interests: The authors have declared that no competing interests exist.

Cobia ( Rachycentron canadum ) support recreational fisheries along the US mid- and south-Atlantic states and have been recently subjected to increased fishing effort, primarily during their spawning season in coastal habitats where increasing temperatures and expanding hypoxic zones are occurring due to climate change. We therefore undertook a study to quantify the physiological abilities of cobia to withstand increases in temperature and hypoxia, including their ability to recover from exhaustive exercise. Respirometry was conducted on cobia from Chesapeake Bay to determine aerobic scope, critical oxygen saturation, ventilation volume and the time to recover from exhaustive exercise under temperature and oxygen conditions projected to be more common in inshore areas by the middle and end of this century. Cobia physiologically tolerated predicted mid- and end-of-century temperatures (28-32°C) and oxygen concentrations as low as 1.7-2.4 mg l -1 . Our results indicated cobia can withstand environmental fluctuations that occur in coastal habitats and the broad environmental conditions their prey items can tolerate. However, at these high temperatures, some cobia did suffer post-exercise mortality. It appears cobia will be able to withstand near-future climate impacts in coastal habitats like Chesapeake Bay, but as conditions worsen, catch-and-release fishing may result in higher mortality than under present conditions., Competing Interests: The authors have no competing interests., (© 2020 The Authors.)

Cancer remains a leading health threat in the United States, and cardiovascular drug toxicity is a primary cause to eliminate a drug from FDA approval. As a result, the demand to develop new anticancer drugs without cardiovascular toxicity is high. Human induced pluripotent stem (iPS) cell-derived tissue chips provide potentially a cost-effective preclinical drug testing platform, including potential avenues for personalized medicine. We have developed a three-dimensional microfluidic device that simultaneously cultures tumor cell spheroids with iPS-derived cardiomyocytes (iPS-CMs) and iPS-derived endothelial cells (iPS-EC). The iPS-derived cells include a GCaMP6 fluorescence reporter to allow real-time imaging to monitor intracellular calcium transients. The multiple-chambered tissue chip features electrodes for pacing of the cardiac tissue to assess cardiomyocyte function such as the maximum capture rate and conduction velocity. We measured the inhibition concentration (IC 50 ) of the anticancer drugs, Doxorubicin (0.1 μM) and Oxaliplatin (4.2 μM), on the tissue chip loaded with colon cancer cells (SW620). We simultaneously evaluated the cardiotoxicity of these anticancer drugs by assessing the drug effect on the spontaneous beat frequency and conduction velocity of iPS-derived cardiac tissue. Consistent with in vivo observations, Doxorubicin reduced the spontaneous beating rate and maximum capture rate at or near the IC 50 (0.04 and 0.22 μM, respectively), whereas the toxicity of Oxaliplatin was only observed at concentrations beyond the IC 50 (33 and 9.9 μM, respectively). Our platform demonstrates the feasibility to simultaneously assess cardiac toxicity and antitumor effects of drugs and could be used to enhance personalized drug testing safety and efficacy. Impact statement Drug development using murine models for preclinical testing is no longer adequate nor acceptable both financially for the pharmaceutical industry as well as for generalized or personalized assessment of safety and efficacy. Innovative solutions using human cells and tissues provide exciting new opportunities. In this study, we report on the creation of a 3D microfluidic device that simultaneously cultures human tumor cell spheroids with cardiomyocytes and endothelial cells derived from the same induced pluripotent stem cell line. The platform provides the opportunity to assess efficacy of anticancer agents while simultaneously screening for potential cardiovascular toxicity in a format conducive for personalized medicine.

Climate change is causing the warming and deoxygenation of coastal habitats like Chesapeake Bay that serve as important nursery habitats for many marine fish species. As conditions continue to change, it is important to understand how these changes impact individual species' behavioral and metabolic performance. The sandbar shark ( Carcharhinus plumbeus ) is an obligate ram-ventilating apex predator whose juveniles use Chesapeake Bay as a nursery ground up to 10 years of age. The objective of this study was to measure juvenile sandbar shark metabolic and behavioral performance as a proxy for overall performance (i.e. fitness or success) when exposed to warm and hypoxic water. Juvenile sandbar sharks (79.5-113.5 cm total length) were collected from an estuary along the eastern shore of Virginia and returned to lab where they were fitted with an accelerometer, placed in a respirometer and exposed to varying temperatures and oxygen levels. Juvenile sandbar shark overall performance declined substantially at 32°C or when dissolved oxygen concentration was reduced below 3.5 mg l -1 (51% oxygen saturation between 24-32°C). As the extent of warm hypoxic water increases in Chesapeake Bay, we expect that the available sandbar shark nursery habitat will be reduced, which may negatively impact the population of sandbar sharks in the western Atlantic as well as the overall health of the ecosystem within Chesapeake Bay.

A strength of physiological ecology is its incorporation of aspects of both species' ecology and physiology; this holistic approach is needed to address current and future anthropogenic stressors affecting elasmobranch fishes that range from overexploitation to the effects of climate change. For example, physiology is one of several key determinants of an organism's ecological niche (along with evolutionary constraints and ecological interactions). The fundamental role of physiology in niche determination led to the development of the field of physiological ecology. This approach considers physiological mechanisms in the context of the environment to understand mechanistic variations that beget ecological trends. Physiological ecology, as an integrative discipline, has recently experienced a resurgence with respect to conservation applications, largely in conjunction with technological advances that extended physiological work from the lab into the natural world. This is of critical importance for species such as elasmobranchs (sharks, skates and rays), which are an especially understudied and threatened group of vertebrates. In 2017, at the American Elasmobranch Society meeting in Austin, Texas, the symposium entitled `Applications of Physiological Ecology in Elasmobranch Research' provided a platform for researchers to showcase work in which ecological questions were examined through a physiological lens. Here, we highlight the research presented at this symposium, which emphasized the strength of linking physiological tools with ecological questions. We also demonstrate the applicability of using physiological ecology research as a method to approach conservation issues, and advocate for a more available framework whereby results are more easily accessible for their implementation into management practices.

While adult white sharks (Carcharodon carcharias) are apex predators with a circumglobal distribution, juvenile white sharks (JWS) feed primarily on bottom dwelling fishes and tend to be coastally associated. Despite the assumedly easier access to juveniles compared to large, migratory adults, limited information is available on the movements, environments, and distributions of individuals during this life stage. To quantify movement and understand their distribution in the southern California Bight, JWS were captured and fitted with dorsal fin-mounted satellite transmitters (SPOT tags; n = 18). Nine individuals crossed the U.S. border into Baja California, Mexico. Individuals used shallow habitats (134.96 ± 191.1 m) close to shore (7.16 ± 5.65 km). A generalized linear model with a binomial distribution was used to predict the presence of individuals based on several environmental predictors from these areas. Juveniles were found to select shallow habitats (< 1000 m deep) close to land (< 30 km of the shoreline) in waters ranging from 14 to 24°C. Southern California was found to be suitable eight months of the year, while coastal habitats in Baja California were suitable year-round. The model predicted seasonal movement with sharks moving from southern California to Baja California during winter. Additionally, habitat distribution changed inter-annually with sharks having a more northerly distribution during years with a higher Pacific Decadal Oscillation index, suggesting sharks may forego their annual fall migrations to Baja California, Mexico, during El Niño years. Model predictions aligned with fishery-dependent catch data, with a greater number of sharks being captured during periods and/or areas of increased habitat suitability. Thus, habitat models could be useful for predicting the presence of JWS in other areas, and can be used as a tool for potentially reducing fishery interactions during seasons and locations where there is increased susceptibility of incidental catch., Competing Interests: The authors have declared that no competing interests exist.

Background/purposes: Human adenovirus (HAdV) infection is prevalent and has an important clinical impact on children. We aim to investigate the molecular epidemiology of HAdV infection and discover the correlations between clinical features and HAdV species in an HAdV outbreak of 2014., Methods: This is a retrospective study, enrolling patients under 19 years of age with HAdV infection at the National Taiwan University Hospital in 2014. We gathered the demographic and clinical data, carried out molecular typing and constructed a phylogenetic tree. Statistical analyses were performed in terms of HAdV species and hospitalization., Results: A total of 531 patients with HAdV infection were identified. HAdV-B accounted for the largest proportion (n = 387, 73%). On average, patients infected with HAdV-E were oldest, whereas those with HAdV-C infection were youngest (p < 0.001). Patients with HAdV-B (HAdV-3) infection were associated with a lower incidence of co-infection with other viruses (p < 0.001). Complications occurred in 203 (38%) patients. There were 149 (28%) patients requiring hospitalization. The risk factors for hospitalization included underlying neurological abnormalities, prematurity and the diagnosis of pneumonia. Five patients (1%) had severe HAdV infection requiring intensive care; all of them fully recovered. The phylogenetic study showed that the partial hexon genes of HAdV-1, HAdV-3, HAdV-4 and HAdV-5 remain stable over time., Conclusion: We established the molecular epidemiology of HAdV infection and demonstrated the relationship between clinical features and HAdV species., (Copyright © 2018. Published by Elsevier B.V.)

During their migrations, marine predators experience varying levels of protection and face many threats as they travel through multiple countries' jurisdictions and across ocean basins. Some populations are declining rapidly. Contributing to such declines is a failure of some international agreements to ensure effective cooperation by the stakeholders responsible for managing species throughout their ranges, including in the high seas, a global commons. Here we use biologging data from marine predators to provide quantitative measures with great potential to inform local, national and international management efforts in the Pacific Ocean. We synthesized a large tracking data set to show how the movements and migratory phenology of 1,648 individuals representing 14 species-from leatherback turtles to white sharks-relate to the geopolitical boundaries of the Pacific Ocean throughout species' annual cycles. Cumulatively, these species visited 86% of Pacific Ocean countries and some spent three-quarters of their annual cycles in the high seas. With our results, we offer answers to questions posed when designing international strategies for managing migratory species.

Background: Passive acoustic telemetry using coded transmitter tags and stationary receivers is a popular method for tracking movements of aquatic animals. Understanding the performance of these systems is important in array design and in analysis. Close proximity detection interference (CPDI) is a condition where receivers fail to reliably detect tag transmissions. CPDI generally occurs when the tag and receiver are near one another in acoustically reverberant settings. Here we confirm transmission multipaths reflected off the environment arriving at a receiver with sufficient delay relative to the direct signal cause CPDI. We propose a ray-propagation based model to estimate the arrival of energy via multipaths to predict CPDI occurrence, and we show how deeper deployments are particularly susceptible., Methods: A series of experiments were designed to develop and validate our model. Deep (300 m) and shallow (25 m) ranging experiments were conducted using Vemco V13 acoustic tags and VR2-W receivers. Probabilistic modeling of hourly detections was used to estimate the average distance a tag could be detected. A mechanistic model for predicting the arrival time of multipaths was developed using parameters from these experiments to calculate the direct and multipath path lengths. This model was retroactively applied to the previous ranging experiments to validate CPDI observations. Two additional experiments were designed to validate predictions of CPDI with respect to combinations of deployment depth and distance. Playback of recorded tags in a tank environment was used to confirm multipaths arriving after the receiver's blanking interval cause CPDI effects., Results: Analysis of empirical data estimated the average maximum detection radius (AMDR), the farthest distance at which 95% of tag transmissions went undetected by receivers, was between 840 and 846 m for the deep ranging experiment across all factor permutations. From these results, CPDI was estimated within a 276.5 m radius of the receiver. These empirical estimations were consistent with mechanistic model predictions. CPDI affected detection at distances closer than 259-326 m from receivers. AMDR determined from the shallow ranging experiment was between 278 and 290 m with CPDI neither predicted nor observed. Results of validation experiments were consistent with mechanistic model predictions. Finally, we were able to predict detection/nondetection with 95.7% accuracy using the mechanistic model's criterion when simulating transmissions with and without multipaths., Discussion: Close proximity detection interference results from combinations of depth and distance that produce reflected signals arriving after a receiver's blanking interval has ended. Deployment scenarios resulting in CPDI can be predicted with the proposed mechanistic model. For deeper deployments, sea-surface reflections can produce CPDI conditions, resulting in transmission rejection, regardless of the reflective properties of the seafloor., Competing Interests: The authors declare that they have no competing interests.

The 2011 release of Fukushima-derived radionuclides into the Pacific Ocean made migratory sharks, teleosts, and marine mammals a source of speculation and anxiety regarding radiocesium ( 134+137 Cs) contamination, despite a lack of actual radiocesium measurements for these taxa. We measured radiocesium in a diverse suite of large predators from the North Pacific Ocean and report no detectable (i.e., ≥ 0.1 Bq kg -1 dry wt) Fukushima-derived 134 Cs in all samples, except in one olive ridley sea turtle (Lepidochelys olivacea) with trace levels (0.1 Bq kg -1 ). Levels of 137 Cs varied within and across taxa, but were generally consistent with pre-Fukushima levels and were lower than naturally occurring 40 K by one to one to two orders of magnitude. Predator size had a weaker effect on 137 Cs and 40 K levels than tissue lipid content. Predator stable isotope values (δ 13 C and δ 15 N) were used to infer recent migration patterns, and showed that predators in the central, eastern, and western Pacific should not be assumed to accumulate detectable levels of radiocesium a priori. Nondetection of 134 Cs and low levels of 137 Cs in diverse marine megafauna far from Fukushima confirms negligible increases in radiocesium, with levels comparable to those prior to the release from Fukushima. Reported levels can inform recently developed models of cesium transport and bioaccumulation in marine species.

We investigate the effect of the Rashba interaction on two dimensional superconductivity. The presence of the Rashba interaction lifts the spin degeneracy and gives rise to the spectrum of two bands. There are intraband and interband pairs scattering which result in the coupled gap equations. We find that there are isotropic and anisotropic components in the gap function. The latter has the form of cos φk where . The former is suppressed because the intraband and the interband scatterings nearly cancel each other. Hence, -the system should exhibit the p-wave superconductivity. We perform a detailed study of electron-phonon interaction for 2DEG and find that, if only normal processes are considered, the effective coupling strength constant of this new superconductivity is about one-half of the s-wave case in the ordinary 2DEG because of the angular average of the additional in the anisotropic gap function. By taking into account of Umklapp processes, we find they are the major contribution in the electron-phonon coupling in superconductivity and enhance the transition temperature Tc.

Background: Mesp1 is critical for early cardiomyocyte differentiation and heart development. We previously observed down-regulation of Mesp1 expression in YY1-ablated mouse embryonic hearts. However, how Mesp1 expression is mediated by YY1 is not well understood., Results: We excised YY1 in the murine embryos using Sox2-cre and found that Mesp1 was down-regulated in the embryonic day (E) 7.5 mutant embryos. Also, YY1 activated the 6 kb Mesp1 regulatory element fused to a luciferase reporter. We identified two putative YY1 binding sites in the proximal promoter region of Mesp1 gene, and found that mutation of these sites significantly reduced YY1-induced activation of the Mesp1 promoter. We also uncovered one cognitive site for SP1, one of the earliest binding partners of YY1 identified. Mutation of this SP1 site repressed SP1-induced activation of the Mesp1 promoter. Moreover, YY1 and SP1 synergistically activated the Mesp1 promoter. Consistently, while Lacz expression driven by the wild-type 6 kb regulatory element of Mesp1 gene was robust in E7.5 mouse embryos, the mutation of these binding sites in the context of this 6 kb sequence substantially reduced the LacZ expression during embryogenesis., Conclusions: YY1 and SP1 independently and cooperatively govern the Mesp1 expression during embryogenesis., (© 2015 Wiley Periodicals, Inc.)

MESP1 is considered the first sign of the nascent cardiac mesoderm and plays a critical role in the appearance of cardiac progenitors, while exhibiting a transient expression in the developing embryo. We profiled the transcriptome of a pure population of differentiating MESP1-marked cells and found that they chiefly contribute to the mesendoderm lineage. High-throughput sequencing of endogenous MESP1-bound DNA revealed that MESP1 preferentially binds to two variants of E-box sequences and activates critical mesendoderm modulators, including Eomes, Gata4, Wnt5a, Wnt5b, Mixl1, T, Gsc, and Wnt3. These mesendoderm markers were enriched in the MESP1 marked population before the appearance of cardiac progenitors and myocytes. Further, MESP1-binding is globally associated with H(3)K(27) acetylation, supporting a novel pivotal role of it in regulating target gene epigenetics. Therefore, MESP1, the pioneer cardiac factor, primarily directs the appearance of mesendoderm, the intermediary of the earliest progenitors of mesoderm and endoderm organogenesis., (© 2015 AlphaMed Press.)

White sharks are highly migratory and segregate by sex, age and size. Unlike marine mammals, they neither surface to breathe nor frequent haul-out sites, hindering generation of abundance data required to estimate population size. A recent tag-recapture study used photographic identifications of white sharks at two aggregation sites to estimate abundance in "central California" at 219 mature and sub-adult individuals. They concluded this represented approximately one-half of the total abundance of mature and sub-adult sharks in the entire eastern North Pacific Ocean (ENP). This low estimate generated great concern within the conservation community, prompting petitions for governmental endangered species designations. We critically examine that study and find violations of model assumptions that, when considered in total, lead to population underestimates. We also use a Bayesian mixture model to demonstrate that the inclusion of transient sharks, characteristic of white shark aggregation sites, would substantially increase abundance estimates for the adults and sub-adults in the surveyed sub-population. Using a dataset obtained from the same sampling locations and widely accepted demographic methodology, our analysis indicates a minimum all-life stages population size of >2000 individuals in the California subpopulation is required to account for the number and size range of individual sharks observed at the two sampled sites. Even accounting for methodological and conceptual biases, an extrapolation of these data to estimate the white shark population size throughout the ENP is inappropriate. The true ENP white shark population size is likely several-fold greater as both our study and the original published estimate exclude non-aggregating sharks and those that independently aggregate at other important ENP sites. Accurately estimating the central California and ENP white shark population size requires methodologies that account for biases introduced by sampling a limited number of sites and that account for all life history stages across the species' range of habitats.

RNA interference (RNAi) is an endogenous post-transcriptional gene regulatory mechanism, where non-coding, double-stranded RNA molecules interfere with the expression of certain genes in order to silence it. Since its discovery, this phenomenon has evolved as powerful technology to diagnose and treat diseases at cellular and molecular levels. With a lot of attention, short interfering RNA (siRNA) therapeutics has brought a great hope for treatment of various undruggable diseases, including genetic diseases, cancer, and resistant viral infections. However, the challenge of their systemic delivery and on how they are integrated to exhibit the desired properties and functions remains a key bottleneck for realizing its full potential. Nanoparticles are currently well known to exhibit a number of unique properties that could be strategically tailored into new advanced siRNA delivery systems. This review summarizes the various nanoparticulate systems developed so far in the literature for systemic delivery of siRNA, which include silica and silicon-based nanoparticles, metal and metal oxides nanoparticles, carbon nanotubes, graphene, dendrimers, polymers, cyclodextrins, lipids, hydrogels, and semiconductor nanocrystals. Challenges and barriers to the delivery of siRNA and the role of different nanoparticles to surmount these challenges are also included in the review.

Virtually all cellular functions involve protein-protein interactions (PPIs). As an increasing number of PPIs are identified and vast amount of information accumulated, researchers are finding different ways to interrogate the data and understand the interactions in context. However, it is widely recognized that a significant portion of the data is scattered, redundant, not considered high quality, and not readily accessible to researchers in a systematic fashion. In addition, it is challenging to identify the optimal protein targets in the current PPI networks. The GeneSense server was developed to integrate gene annotation and PPI networks in an expandable architecture that incorporates selected databases with the aim to assemble, analyze, evaluate and disseminate protein-protein association information in a comprehensive and user-friendly manner. Three network models including nodenet, leafnet and loopnet are used to identify the optimal protein targets in the complex networks. GeneSense is freely available at www.biomedsense.org/genesense.php.

Aim: The aim of this work is to evaluate combining targeting strategy and convection-enhanced delivery in brain tumor models by imaging quantum dot-immunoliposome hybrid nanoparticles., Materials & Methods: An EGF receptor-targeted, quantum dot-immunoliposome hybrid nanoparticle (QD-IL) was synthesized. In vitro uptake was measured by flow cytometry and intracellular localization was imaged by confocal microscopy. In the in vivo study, QD-ILs were delivered to intracranial xenografts via convection-enhanced delivery and fluorescence was monitored noninvasively in real-time., Results: QD-ILs exhibited specific and efficient uptake in vitro and exhibited approximately 1.3- to 5.0-fold higher total fluorescence compared with nontargeted counterpart in intracranial brain tumor xenografts in vivo., Conclusion: QD-ILs serve as an effective imaging agent in vitro and in vivo, and the data suggest that ligand-directed liposomal nanoparticles in conjunction with convection-enhanced delivery may offer therapeutic benefits for glioblastoma treatment as a result of specific and efficient uptake by malignant cells.

Unique insights for the reprograming of cell lineages have come from embryonic development in the ascidian Ciona, which is dependent upon the transcription factors Ci-ets1/2 and Ci-mesp to generate cardiac progenitors. We tested the idea that mammalian v-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) and mesoderm posterior (MESP) homolog may be used to convert human dermal fibroblasts into cardiac progenitors. Here we show that murine ETS2 has a critical role in directing cardiac progenitors during cardiopoiesis in embryonic stem cells. We then use lentivirus-mediated forced expression of human ETS2 to convert normal human dermal fibroblasts into replicative cells expressing the cardiac mesoderm marker KDR(+). However, although neither ETS2 nor the purported cardiac master regulator MESP1 can by themselves generate cardiac progenitors de novo from fibroblasts, forced coexpression of ETS2 and MESP1 or cell treatment with purified proteins reprograms fibroblasts into cardiac progenitors, as shown by the de novo appearance of core cardiac transcription factors, Ca(2+) transients, and sarcomeres. Our data indicate that ETS2 and MESP1 play important roles in a genetic network that governs cardiopoiesis.

This study presents the first data on movement, habitat use and behaviour for yellowfin tuna Thunnus albacares in the Atlantic Basin. Six individuals were tracked in the Gulf of Mexico using pop-up satellite archival tags. Records up to 80 days in length were obtained, providing information on depth and temperature preferences as well as horizontal movements. Thunnus albacares in the Gulf of Mexico showed a strong preference for the mixed layer and thermocline, consistent with findings for this species in other ocean basins. Fish showed a diel pattern in depth distribution, remaining in surface and mixed layer waters at night and diving to deeper waters during the day. The vertical extent of T. albacares habitat appeared to be temperature limited, with fish generally avoiding waters that were >6 degrees C cooler than surface waters. The vertical and thermal habitat usage of T. albacares differs from that of bigeye Thunnus obesus and bluefin Thunnus thynnus, Thunnus orientalis and Thunnus maccoyii tunas. These results are consistent with the results of earlier studies conducted on T. albacares in other oceans.

Targeted drug delivery systems that combine imaging and therapeutic modalities in a single macromolecular construct may offer advantages in the development and application of nanomedicines. To incorporate the unique optical properties of luminescent quantum dots (QDs) into immunoliposomes for cancer diagnosis and treatment, we describe the synthesis, biophysical characterization, tumor cell-selective internalization, and anticancer drug delivery of QD-conjugated immunoliposome-based nanoparticles (QD-ILs). Pharmacokinetic properties and in vivo imaging capability of QD-ILs were also investigated. Freeze-fracture electron microscopy was used to visualize naked QDs, liposome controls, nontargeted QD-conjugated liposomes (QD-Ls), and QD-ILs. QD-ILs prepared by insertion of anti-HER2 scFv exhibited efficient receptor-mediated endocytosis in HER2-overexpressing SK-BR-3 and MCF-7/HER2 cells but not in control MCF-7 cells as analyzed by flow cytometry and confocal microscopy. In contrast, nontargeted QD-Ls showed minimal binding and uptake in these cells. Doxorubicin-loaded QD-ILs showed efficient anticancer activity, while no cytotoxicity was observed for QD-ILs without chemotherapeutic payload. In athymic mice, QD-ILs significantly prolonged circulation of QDs, exhibiting a plasma terminal half-life ( t 1/2) of approximately 2.9 h as compared to free QDs with t 1/2 < 10 min. In MCF-7/HER2 xenograft models, localization of QD-ILs at tumor sites was confirmed by in vivo fluorescence imaging.

In an effort to use model fluid membranes for immunological studies, we compared the formation of planar phospholipid bilayers supported on silicon dioxide surfaces with and without incorporation of glycolipids as the antigen for in situ antibody binding. Dynamic light scattering measurements did not differentiate the hydrodynamic volumes of extruded small unilamellar vesicles (E-SUVs) containing physiologically relevant concentrations (0.5-5 mol%) of monosialoganglioside GM1 (GM1) from exclusive egg yolk L-alpha-phosphatidylcholine (egg PC) E-SUVs. However, quantifiable differences in deposition mass and dissipative energy loss emerged in the transformation of 5 mol% GM1/95 mol% egg PC E-SUVs to planar supported lipid bilayers (PSLBs) by vesicle fusion on thermally evaporated SiO2, as monitored by the quartz crystal microbalance with dissipation (QCM-D) technique. Compared to the 100 mol% egg PC bilayers on the same surface, E-SUVs containing 5 mol% GM1 reached a approximately 12% higher mass and a lower dissipative energy loss during bilayer transformation. PSLBs with 5 mol% GM1 are approximately 18% heavier than 100 mol% egg PC and approximately 11% smaller in projected area per lipid, indicating an increased rigidity and a tighter packing. Subsequent binding of polyclonal immunoglobulin G anti-GM1 to the PSLBs was performed in situ and showed specificity. The anti-GM1 to GM1 ratios at equilibrium were roughly proportional to the concentrations of anti-GM1 administered in the solution. Fluorescence recovery after photobleaching was utilized to verify the retained, albeit reduced lateral fluidity of the supported membranes. Five moles percentage of GM1 membranes (GM1 to PC ratio approximately 1:19) decorated with 1 mol% N-(Texas Red sulfonyl)-1,2-dihexadecanoyl-sn-glycerol-3-phosphoethanolamine (Texas Red DHPE) exhibited an approximately 16% lower diffusion coefficient of 1.32+/-0.06 microm2/s, compared to 1.58+/-0.04 microm2/s for egg PC membranes without GM1 (p<0.01). The changes in vesicle properties and membrane lateral fluidity are attributed to the interactions of GM1 with itself and GM1 with other membrane lipids. This system allows for molecules of interest such as GM1 to exist on a more biologically relevant surface than those used in conventional methods such as ELISA. Our analysis of rabbit serum antibodies binding to GM1 demonstrates this platform can be used to test for the presence of anti-lipid antibodies in serum.

Shark populations are declining globally, yet the movements and habitats of most species are unknown. We used a satellite tag attached to the dorsal fin to track salmon sharks (Lamna ditropis) for up to 3.2 years. Here we show that salmon sharks have a subarctic-to-subtropical niche, ranging from 2 degrees to 24 degrees C, and they spend winter periods in waters as cold as 2 degrees to 8 degrees C. Functional assays and protein gels reveal that the expression of excitation-contraction coupling proteins is enhanced in salmon shark hearts, which may underlie the shark's ability to maintain heart function at cold temperatures and their niche expansion into subarctic seas.

Electronic tags that archive or transmit stored data to satellites have advanced the mapping of habitats used by highly migratory fish in pelagic ecosystems. Here we report on the electronic tagging of 772 Atlantic bluefin tuna in the western Atlantic Ocean in an effort to identify population structure. Reporting electronic tags provided accurate location data that show the extensive migrations of individual fish (n = 330). Geoposition data delineate two populations, one using spawning grounds in the Gulf of Mexico and another from the Mediterranean Sea. Transatlantic movements of western-tagged bluefin tuna reveal site fidelity to known spawning areas in the Mediterranean Sea. Bluefin tuna that occupy western spawning grounds move to central and eastern Atlantic foraging grounds. Our results are consistent with two populations of bluefin tuna with distinct spawning areas that overlap on North Atlantic foraging grounds. Electronic tagging locations, when combined with US pelagic longline observer and logbook catch data, identify hot spots for spawning bluefin tuna in the northern slope waters of the Gulf of Mexico. Restrictions on the time and area where longlining occurs would reduce incidental catch mortalities on western spawning grounds.

Planar supported lipid bilayers have attracted immense interest for their properties as model cell membranes and for potential applications in biosensors and lab-on-a-chip devices. We report the formation of fluid planar biomembranes on hydrophilic silica aerogels and xerogels. Scanning electron microscopy results showed the presence of interconnected silica beads of approximately 10-25 nm in diameter and nanoscale open pores of comparable size for the aerogel and grain size of approximately 36-104 nm with approximately 9-24 nm diameter pores for the xerogel. When the aerogel/xerogel was prehydrated and then allowed to incubate in l-alpha-phosphatidylcholine (egg yolk PC) unilamellar vesicle (approximately 30 nm diameter) solution, lipid bilayers were formed due to the favorable interaction of vesicles with the hydroxyl-abundant silica surface. Lateral mobility of labeled lipid N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine was retained in the membranes. A diffusion coefficient of 0.61 +/- 0.22 microm(2)/s was determined from fluorescence recovery after photobleaching analysis for membranes on aerogels, compared to 2.46 +/- 0.35 microm(2)/s on flat glass. Quartz crystal microbalance-dissipation was utilized to monitor the kinetics of the irreversible adsorption and fusion of vesicles into bilayers on xerogel thin films.