An Indocyanine Green-Based Nanoprobe for In Vivo Detection of Cellular Senescence.

There is an urgent need to improve conventional cancer-treatments by preventing detrimental side effects, cancer recurrence and metastases. Recent studies have shown that presence of senescent cells in tissues treated with chemo- or radiotherapy can be used to predict the effectiveness of cancer treatment. However, although the accumulation of senescent cells is one of the hallmarks of cancer, surprisingly little progress has been made in development of strategies for their detection in vivo. To address a lack of detection tools, we developed a biocompatible, injectable organic nanoprobe (NanoJagg), which is selectively taken up by senescent cells and accumulates in the lysosomes. The NanoJagg probe is obtained by self-assembly of indocyanine green (ICG) dimers using a scalable manufacturing process and characterized by a unique spectral signature suitable for both photoacoustic tomography (PAT) and fluorescence imaging. In vitro, ex vivo and in vivo studies all indicate that NanoJaggs are a clinically translatable probe for detection of senescence and their PAT signal makes them suitable for longitudinal monitoring of the senescence burden in solid tumors after chemotherapy or radiotherapy.

Oocyte dynamics for Atlantic bluefin tuna (Thunnus thynnus) in the southern Gulf of Mexico: A comparative assessment of Mediterranean spawners using two stereological methods.

Although most research focused on the northern Gulf of Mexico for western Atlantic bluefin tuna, the histological records of reproductive activity of this species in the southern Gulf of Mexico (Mexican waters) have been presented for the first time. This work is the first to study oocyte dynamics in Atlantic bluefin tuna caught in the southern Gulf of Mexico by assessing and comparing them with Mediterranean stock (BFT-E) through stereology using two different methods. Regardless of Atlantic bluefin tuna females returning to their respective spawning grounds at different months in the southern Gulf of Mexico and the Mediterranean, both stocks arrived reproductively inactive and remained in these zones during periods of similar length; they were reproductively active until March for the southern Gulf of Mexico and May for the Mediterranean females. The comparison of the size structure between the two stocks examined using kernel density estimators demonstrated a quite remarkable difference in mean fork lengths between stocks. The ovarian oocyte density, that is, the number of oocytes per gram of ovary, for each gonad stage predicted using the Weibel and Gomez and oocyte packing density (OPD) methods did not significantly differ between stocks and showed that advanced vitellogenic oocytes from spawning-capable females are an appropriate indicator to estimate potential fecundity, presenting values of c. 1273 and ~1355 eggs per gram for the southern Gulf of Mexico and Mediterranean females, respectively. Females caught in Mexican waters (southern Gulf of Mexico) were larger than those caught in the Mediterranean; however, it was demonstrated that the length and weight of females did not affect ovarian oocyte density production. In addition, densities estimated for each gonad stage using W&G and OPD methods did not differ between stocks and presented equal patterns in their oocyte dynamics. These findings contribute to a better understanding of the reproductive biology of Atlantic bluefin tuna, especially in the southern Gulf of Mexico, due to the lack of information regarding this zone, and may allow to support strategies for proper assessment, management, and conservation.

S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate.

R-2-hydroxyglutarate accumulates to millimolar levels in cancer cells with gain-of-function isocitrate dehydrogenase 1/2 mutations. These levels of R-2-hydroxyglutarate affect 2-oxoglutarate-dependent dioxygenases. Both metabolite enantiomers, R- and S-2-hydroxyglutarate, are detectible in healthy individuals, yet their physiological function remains elusive. Here we show that 2-hydroxyglutarate accumulates in mouse CD8+ T cells in response to T-cell receptor triggering, and accumulates to millimolar levels in physiological oxygen conditions through a hypoxia-inducible factor 1-alpha (HIF-1α)-dependent mechanism. S-2-hydroxyglutarate predominates over R-2-hydroxyglutarate in activated T cells, and we demonstrate alterations in markers of CD8+ T-cell differentiation in response to this metabolite. Modulation of histone and DNA demethylation, as well as HIF-1α stability, mediate these effects. S-2-hydroxyglutarate treatment greatly enhances the in vivo proliferation, persistence and anti-tumour capacity of adoptively transferred CD8+ T cells. Thus, S-2-hydroxyglutarate acts as an immunometabolite that links environmental context, through a metabolic-epigenetic axis, to immune fate and function.

Comparison of the Capacitance of a Cyclically Fatigued Stretch Sensor to a Non-Fatigued Stretch Sensor When Performing Static and Dynamic Foot-Ankle Motions.

Motion capture is the current gold standard for assessing movement of the human body, but laboratory settings do not always mimic the natural terrains and movements encountered by humans. To overcome such limitations, a smart sock that is equipped with stretch sensors is being developed to record movement data outside of the laboratory. For the smart sock stretch sensors to provide valuable feedback, the sensors should have durability of both materials and signal. To test the durability of the stretch sensors, the sensors were exposed to high-cycle fatigue testing with simultaneous capture of the capacitance. Following randomization, either the fatigued sensor or an unfatigued sensor was placed in the plantarflexion position on the smart sock, and participants were asked to complete the following static movements: dorsiflexion, inversion, eversion, and plantarflexion. Participants were then asked to complete gait trials. The sensor was then exchanged for either an unfatigued or fatigued plantarflexion sensor, depending upon which sensor the trials began with, and each trial was repeated by the participant using the opposite sensor. Results of the tests show that for both the static and dynamic movements, the capacitive output of the fatigued sensor was consistently higher than that of the unfatigued sensor suggesting that an upwards drift of the capacitance was occurring in the fatigued sensors. More research is needed to determine whether stretch sensors should be pre-stretched prior to data collection, and to also determine whether the drift stabilizes once the cyclic softening of the materials comprising the sensor has stabilized.

Targeting HIF2α-ARNT hetero-dimerisation as a novel therapeutic strategy for pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a destructive disease of the pulmonary vasculature often leading to right heart failure and death. Current therapeutic intervention strategies only slow disease progression. The role of aberrant hypoxia-inducible factor (HIF)2α stability and function in the initiation and development of pulmonary hypertension (PH) has been an area of intense interest for nearly two decades.Here we determine the effect of a novel HIF2α inhibitor (PT2567) on PH disease initiation and progression, using two pre-clinical models of PH. Haemodynamic measurements were performed, followed by collection of heart, lung and blood for pathological, gene expression and biochemical analysis. Blood outgrowth endothelial cells from idiopathic PAH patients were used to determine the impact of HIF2α-inhibition on endothelial function.Global inhibition of HIF2a reduced pulmonary vascular haemodynamics and pulmonary vascular remodelling in both su5416/hypoxia prevention and intervention models. PT2567 intervention reduced the expression of PH-associated target genes in both lung and cardiac tissues and restored plasma nitrite concentration. Treatment of monocrotaline-exposed rodents with PT2567 reduced the impact on cardiovascular haemodynamics and promoted a survival advantage. In vitro, loss of HIF2α signalling in human pulmonary arterial endothelial cells suppresses target genes associated with inflammation, and PT2567 reduced the hyperproliferative phenotype and overactive arginase activity in blood outgrowth endothelial cells from idiopathic PAH patients. These data suggest that targeting HIF2α hetero-dimerisation with an orally bioavailable compound could offer a new therapeutic approach for PAH. Future studies are required to determine the role of HIF in the heterogeneous PAH population.

Genetic validation of the unexpected presence of a tropical tuna, bigeye tuna (Thunnus obesus), in the Mediterranean.

Bigeye tuna (Thunnus obesus, Lowe, 1839) is one of the eight recognized species of the genus Thunnus. It is considered a tropical species distributed in the Atlantic, Pacific and Indian Oceans. To date, no validated presence of this species has been reported inside the Mediterranean Sea. This study, however, confirms, for the first time, the presence of three young individuals of this species within the Mediterranean Sea.

HIF2α-arginase axis is essential for the development of pulmonary hypertension.

Hypoxic pulmonary vasoconstriction is correlated with pulmonary vascular remodeling. The hypoxia-inducible transcription factors (HIFs) HIF-1α and HIF-2α are known to contribute to the process of hypoxic pulmonary vascular remodeling; however, the specific role of pulmonary endothelial HIF expression in this process, and in the physiological process of vasoconstriction in response to hypoxia, remains unclear. Here we show that pulmonary endothelial HIF-2α is a critical regulator of hypoxia-induced pulmonary arterial hypertension. The rise in right ventricular systolic pressure (RVSP) normally observed following chronic hypoxic exposure was absent in mice with pulmonary endothelial HIF-2α deletion. The RVSP of mice lacking HIF-2α in pulmonary endothelium after exposure to hypoxia was not significantly different from normoxic WT mice and much lower than the RVSP values seen in WT littermate controls and mice with pulmonary endothelial deletion of HIF-1α exposed to hypoxia. Endothelial HIF-2α deletion also protected mice from hypoxia remodeling. Pulmonary endothelial deletion of arginase-1, a downstream target of HIF-2α, likewise attenuated many of the pathophysiological symptoms associated with hypoxic pulmonary hypertension. We propose a mechanism whereby chronic hypoxia enhances HIF-2α stability, which causes increased arginase expression and dysregulates normal vascular NO homeostasis. These data offer new insight into the role of pulmonary endothelial HIF-2α in regulating the pulmonary vascular response to hypoxia.

Lower-Extremity Kinematics During Ankle Inversion Perturbations: A Novel Experimental Protocol That Simulates an Unexpected Lateral Ankle Sprain Mechanism.

CONTEXT: Lateral ankle sprains are a common injury in which the mechanics of injury have been extensively studied. However, the anticipatory mechanisms to ankle inversion perturbations are not well understood. OBJECTIVE: To examine lower-extremity kinematics, including spatial and temporal variables of maximum inversion displacement and maximum inversion velocity, during landings on a tilted surface using a new experimental protocol to replicate a lateral ankle sprain. SETTING: Three-dimensional motion analysis laboratory. PARTICIPANTS: A total of 23 healthy adults. INTERVENTIONS: Participants completed unexpected (UE) and expected (EXP) unilateral landings onto a tilted surface rotated 25° in the frontal plane from a height of 30 cm. MAIN OUTCOME MEASURES: Ankle, knee, and hip kinematics at each discrete time point from 150 ms pre-initial contact (IC) to 150 ms post-IC, in addition to maximum ankle inversion and maximum inversion velocity, were compared between UE and EXP landings. RESULTS: The UE landing produced significantly greater maximum inversion displacement (P < .01) and maximum inversion velocity (P = .02) than the EXP landing. Significantly less ankle inversion and internal rotation were found during pre-IC, whereas during post-IC, significantly greater ankle inversion, ankle internal rotation, knee flexion, and knee abduction were observed for the UE landing (P < .05). In addition, significantly less hip flexion and hip adduction were observed for the UE landing during pre-IC and post-IC (P < .05). CONCLUSIONS: Differences in the UE and EXP landings indicate the experimental protocol presented a UE inversion perturbation that approximates the mechanism of a lateral ankle sprain. Furthermore, knowledge of the inversion perturbation elicited a hip-dominant strategy, which may be utilized to assist with ankle joint stabilization during landing to further protect the lateral ankle from injury.

Microvascular replantation of a composite facial avulsion in a 24-month-old child after dog bite.

Dog bite injuries are common sources of morbidity with an estimated incidence of 4.5 million bites per year with over 350,000 requiring treatment in the emergency room. Children under the age of 14 are most likely to be affected with a peak age of 5-9 years old. We report a case of a 24-month-old female who sustained a large composite facial avulsion injury from a pit bull dog bite. The avulsed tissue involved a substantial portion of the patient's mid-face, including the entire soft tissue of the nose, upper lip, part of the left cheek, and left oral commissure. Artery-only microvascular replantation was performed because no recipient vein could be identified from the facial defect. Medicinal leech therapy was used for eight days postoperatively to prevent venous congestion. The patient experienced significant blood loss due to leech therapy and required nearly 29 L of blood product replacement. At the last follow up of 8 months postoperatively, the patient was recovering well with significant improvement in function and cosmesis of the mid-face. This case describes a successful artery-only replantation of an avulsive bite injury to the face of a young child. Despite the technical difficulty of cases such as this one, microvascular replantation should be attempted because when successful it provides a superior cosmetic and functional result to other reconstructive techniques.

Selective accumulation of biotin in arterial chemoreceptors: requirement for carotid body exocytotic dopamine secretion.

KEY POINTS: Biotin, a vitamin whose main role is as a coenzyme for carboxylases, accumulates at unusually large amounts within cells of the carotid body (CB). In biotin-deficient rats biotin rapidly disappears from the blood; however, it remains at relatively high levels in CB glomus cells. The CB contains high levels of mRNA for SLC5a6, a biotin transporter, and SLC19a3, a thiamine transporter regulated by biotin. Animals with biotin deficiency exhibit pronounced metabolic lactic acidosis. Remarkably, glomus cells from these animals have normal electrical and neurochemical properties. However, they show a marked decrease in the size of quantal dopaminergic secretory events. Inhibitors of the vesicular monoamine transporter 2 (VMAT2) mimic the effect of biotin deficiency. In biotin-deficient animals, VMAT2 protein expression decreases in parallel with biotin depletion in CB cells. These data suggest that dopamine transport and/or storage in small secretory granules in glomus cells depend on biotin. ABSTRACT: Biotin is a water-soluble vitamin required for the function of carboxylases as well as for the regulation of gene expression. Here, we report that biotin accumulates in unusually large amounts in cells of arterial chemoreceptors, carotid body (CB) and adrenal medulla (AM). We show in a biotin-deficient rat model that the vitamin rapidly disappears from the blood and other tissues (including the AM), while remaining at relatively high levels in the CB. We have also observed that, in comparison with other peripheral neural tissues, CB cells contain high levels of SLC5a6, a biotin transporter, and SLC19a3, a thiamine transporter regulated by biotin. Biotin-deficient rats show a syndrome characterized by marked weight loss, metabolic lactic acidosis, aciduria and accelerated breathing with normal responsiveness to hypoxia. Remarkably, CB cells from biotin-deficient animals have normal electrophysiological and neurochemical (ATP levels and catecholamine synthesis) properties; however, they exhibit a marked decrease in the size of quantal catecholaminergic secretory events, which is not seen in AM cells. A similar differential secretory dysfunction is observed in CB cells treated with tetrabenazine, a selective inhibitor of the vesicular monoamine transporter 2 (VMAT2). VMAT2 is highly expressed in glomus cells (in comparison with VMAT1), and in biotin-deficient animals VMAT2 protein expression decreases in parallel with the decrease of biotin accumulated in CB cells. These data suggest that biotin has an essential role in the homeostasis of dopaminergic transmission modulating the transport and/or storage of transmitters within small secretory granules in glomus cells.

Carotid body oxygen sensing and adaptation to hypoxia.

The carotid body (CB) is the principal arterial chemoreceptor that mediates the hyperventilatory response to hypoxia. Our understanding of CB function and its role in disease mechanisms has progressed considerably in the last decades, particularly in recent years. The sensory elements of the CB are the neuron-like glomus cells, which contain numerous transmitters and form synapses with afferent sensory fibers. The activation of glomus cells under hypoxia mainly depends on the modulation of O2-sensitive K(+) channels which leads to cell depolarization and the opening of Ca(2+) channels. This model of sensory transduction operates in all mammalian species studied thus far, including man. However, the molecular mechanisms underlying the modulation of ion channel function by changes in the O2 level are as yet unknown. The CB plays a fundamental role in acclimatization to sustained hypoxia. Mice with CB atrophy or patients who have undergone CB resection due to surgical treatments show a marked intolerance to even mild hypoxia. CB growth under hypoxia is supported by the existence of a resident population of neural crest-derived stem cells of glia-like phenotype. These stem cells are not highly affected by exposure to low O2 tension; however, there are abundant synapse-like contacts between the glomus cells and stem cells (chemoproliferative synapses), which may be needed to trigger progenitor cell proliferation and differentiation under hypoxia. CB hypo- or hyper-activation may also contribute to the pathogenesis of several prevalent human diseases.

Ecology of the Atlantic black skipjack Euthynnus alletteratus (Osteichthyes: Scombridae) in the western Mediterranean Sea inferred by parasitological analysis.

Between 2008 and 2011, the head of 150 Euthynnus alletteratus (Osteichthyes: Scombridae) caught inshore off the southeastern Iberian coast (western Mediterranean Sea) were examined for parasites. Two monogeneans, four didymozoid trematodes and four copepods were found. Parasite abundance showed a positive relationship with the annual sea surface temperature, except for Pseudocycnus appendiculatus, but negative with the sea depth (Capsala manteri, Neonematobothrium cf. kawakawa and Caligus bonito). Prevalences and mean abundances differed significantly among sampling areas, except for C. manteri, Oesophagocystis sp. 2 and Ceratocolax euthynni, and sampling years (Melanocystis cf. kawakawa, N.cf. kawakawa, P. appendiculatus and Unicolax collateralis). Results indicate that the parasite abundances of E. alletteratus in the western Mediterranean Sea depend mainly on regional environmental variables, which can show interannual variations. The presence of pelagic parasites, i.e. didymozoids and P. appendiculatus, could indicate that E. alletteratus migrates between inshore and offshore pelagic domains. The different parasite faunas reported in E. alletteratus populations from the western Atlantic Ocean and the Mediterranean Sea appear to point out the geographical host isolation. These results suggest that E. alletteratus inhabiting the western Mediterranean Sea performs inshore-offshore small-scale migrations, and not transoceanic migrations between the western Atlantic Ocean and Mediterranean Sea.

Low-Level Laser Therapy at 635 nm for Treatment of Chronic Plantar Fasciitis: A Placebo-Controlled, Randomized Study.

Plantar fasciitis affects nearly 1 million persons in the United States at any one time. Conservative therapies have been reported to successfully treat 90% of plantar fasciitis cases; however, for the remaining cases, only invasive therapeutic solutions remain. This investigation studied newly emerging technology, low-level laser therapy. From September 2011 to June 2013, 69 subjects were enrolled in a placebo-controlled, randomized, double-blind, multicenter study that evaluated the clinical utility of low-level laser therapy for the treatment of unilateral chronic fasciitis. The volunteer participants were treated twice a week for 3 weeks for a total of 6 treatments and were evaluated at 5 separate time points: before the procedure and at weeks 1, 2, 3, 6, and 8. The pain rating was recorded using a visual analog scale, with 0 representing "no pain" and 100 representing "worst pain." Additionally, Doppler ultrasonography was performed on the plantar fascia to measure the fascial thickness before and after treatment. Study participants also completed the Foot Function Index. At the final follow-up visit, the group participants demonstrated a mean improvement in heel pain with a visual analog scale score of 29.6 ± 24.9 compared with the placebo subjects, who reported a mean improvement of 5.4 ± 16.0, a statistically significant difference (p < .001). Although additional studies are warranted, these data have demonstrated that low-level laser therapy is a promising treatment of plantar fasciitis.

Implanted neural progenitor cells regulate glial reaction to brain injury and establish gap junctions with host glial cells.

Transplantation of neural stem/progenitor cells (NPCs) in the lesioned brain is able to restore morphological and physiological alterations induced by different injuries. The local microenvironment created at the site of grafting and the communication between grafted and host cells are crucial in the beneficial effects attributed to the NPC implants. We have previously described that NPC transplantation in an animal model of central axotomy restores firing properties and synaptic coverage of lesioned neurons and modulates their trophic factor content. In this study, we aim to explore anatomical relationships between implanted NPCs and host glia that might account for the implant-induced neuroprotective effects. Postnatal rat subventricular zone NPCs were isolated and grafted in adult rats after transection of the medial longitudinal fascicle. Brains were removed and analyzed eight weeks later. Immunohistochemistry for different glial markers revealed that NPC-grafted animals displayed significantly greater microglial activation than animals that received only vehicle injections. Implanted NPCs were located in close apposition to activated microglia and reactive astrocytes. The gap junction protein connexin43 was present in NPCs and glial cells at the lesion site and was often found interposed within adjacent implanted and glial cells. Gap junctions were identified between implanted NPCs and host astrocytes and less frequently between NPCs and microglia. Our results show that implanted NPCs modulate the glial reaction to lesion and establish the possibility of communication through gap junctions between grafted and host glial cells which might be involved in the restorative effects of NPC implants.

Interannual differences for sea turtles bycatch in Spanish longliners from Western Mediterranean Sea.

Recent studies showed that regional abundance of loggerhead and leatherback turtles could oscillate interannually according to oceanographic and climatic conditions. The Western Mediterranean is an important fishing area for the Spanish drifting longline fleet, which mainly targets swordfish, bluefin tuna, and albacore. Due to the spatial overlapping in fishing activity and turtle distribution, there is an increasing sea turtle conservation concern. The main goal of this study is to analyse the interannual bycatch of loggerhead and leatherback turtles by the Spanish Mediterranean longline fishery and to test the relationship between the total turtle by-catch of this fishery and the North Atlantic Oscillation (NAO). During the 14 years covered in this study, the number of sea turtle bycatches was 3,940 loggerhead turtles and 8 leatherback turtles, 0.499 loggerhead turtles/1000 hooks and 0.001014 leatherback turtles/1000 hooks. In the case of the loggerhead turtle the positive phase of the NAO favours an increase of loggerhead turtles in the Western Mediterranean Sea. However, in the case of leatherback turtle the negative phase of the NAO favours the presence of leatherback turtle. This contraposition could be related to the different ecophysiological response of both species during their migration cycle.

Patterns of Discordance Between Clinical and Pathologic Stage in Head and Neck Cancer.

OBJECTIVE: To enhance understanding in patterns of discordance between clinical and pathological T and N staging in multiple sites of head and neck squamous cell cancer. METHODS: A retrospective cohort of 580 newly diagnosed and surgically treated head and neck squamous cell carcinoma patients from a single institution over a 10-year period are presented. Clinical and pathologic staging are compared. RESULTS: Notably, 33% of cases had staging discordance. Overall Cohen's kappa agreement was κ = 0.55 (moderate agreement). Highly discordant site stages with κ < 0.45 included: T2 oral cavity, T2 oropharynx, T3 larynx, and N1 lymph node. T2-4 oral cavity cancers were often overstaged, and more than one-third of T3 larynx cancers were understaged. Highly concordant site stages with κ>0.65 included: T1 larynx, T4 oropharynx, N0 lymph node, and N3 lymph node. CONCLUSION: There exists a quantifiable and, in certain sites, clinically relevant pattern of discordance between clinical and pathologic staging. Tumor board multidisciplinary evaluation can highlight these discrepancies and aide in limiting effects on treatment decisions. However, discordant staging can affect the interpretation and application of prognostication, treatment, and data accuracy. Further investigation is warranted to improve clinical staging accuracy in areas of highest discordance. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Atlantic bonito (Sarda) genomic analysis reveals population differentiation across Northeast Atlantic and mediterranean locations: Implications for fishery management.

The Atlantic bonito (Sarda, family Scombridae) is a pelagic species and one of the most exploited small tuna species. Despite its economic importance, biological information is scarce with no associated management directives. In this study, using a population genomic approach resulted in a lack of panmixia of two genetic pools with different effective population sizes (east central-tropical Atlantic and northeast Atlantic-Mediterranean) and an intermixing zone in Atlantic Morocco. The absence of genetic heterogeneity between the locations in Atlantic - Mediterranean transitional zone adds new evidence that challenges the Strait of Gibraltar as a phylogeographic barrier for marine pelagic species. These results are proposed to the ICCAT Commission to establish management areas for this species, although they are not consistent with the recently adopted pelagic ecoregions. Finally, a panel of highly informative SNPs was developed for efficient and low-cost population assignment and the analysis of unresolved population structures.

The relative importance of biological and environmental factors on the trophodynamics of a pelagic marine predator, the blue shark (Prionace glauca).

Marine ecosystems have been significantly altered by the cumulative impacts of human activities. Pelagic sharks have become vulnerable to increases in mortality rates caused by fishing. The decrease in number of these top predators could have substantial cascading effects on wider marine communities. Concerns about these potential impacts, and the critical need for effective management, have led to an increased interest in assessing the trophic ecology of sharks. While stable isotope analyses have been used to provide relevant insights about the trophic ecology of sharks, the causal factors leading to trophic variation between individuals has been largely overlooked. Here, we investigated the relative effect of biological factors, geographic location, and environmental factors on the spatial trophodynamics of the blue shark (Prionace glauca). Specifically, stable isotope values of δ15N and δ13C, and the estimated trophic position (TP) were analysed for 180 blue sharks collected from south of the Canary Islands in the Atlantic Ocean, to the north-western Mediterranean Sea. The results showed that models which included combined variables explained the variation in δ15N, TP and δ13C values better than models which considered only stand-alone predictors. The independent contributions of environmental variables and biological factors seemed to be more important than geographic location for δ15N and TP. δ15N and TP increased in a curvilinear fashion with body size, and TP was higher for females. In the case of δ13C values, only an effect from sex was observed. Among environmental variables, chlorophyll-a, pelagic productivity, and sea-surface temperature proved to be reliable predictors, particularly for δ15N and TP, most likely due to their relationship with productivity and prey availability. This study provides new information on ranking the factors that influence the trophodynamics of the blue shark, namely the environment, the geographic location, and the biological factors of the species.

Assessing juvenile swordfish (Xiphias gladius) diet as an indicator of marine ecosystem changes in the northwestern Mediterranean Sea.

To preserve marine biodiversity, we need reliable early warning indicators that inform changes in marine ecosystems. As reliable samplers of mid-trophic level communities, studying the trophodynamics of large pelagic fish can contribute to monitoring these changes. Here, we combined stomach content and stable isotope analyses to reconstruct the diet of juvenile swordfish (Xiphias gladius) in the northwestern Mediterranean Sea, in a time-lapse of almost a decade (2012 and 2020). Overall, our study showed that swordfish fed on a wide range of fish and cephalopod species from both pelagic and demersal habitats. A dietary shift towards increasing consumption of cephalopods and decreasing consumption of Gadiformes had been observed between 2012 and 2020. Stable isotope approaches revealed that gelatinous organisms were also important prey, particularly for smaller-sized swordfish. We underline the importance of combining multiple and complementary approaches to better reconstruct the diet of generalist species. Our findings highlight the generalist and opportunistic diet of Mediterranean swordfish, which makes them good candidates for monitoring changes in the ecosystem.