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In this communication we introduce marmap, a package designed for downloading, plotting and manipulating bathymetric and topographic data in R. marmap can query the ETOPO1 bathymetry and topography database hosted by the NOAA, use simple latitude-longitude-depth data in ascii format, and take advantage of the advanced plotting tools available in R to build publication-quality bathymetric maps. Functions to query data (bathymetry, sampling information…) are available interactively by clicking on marmap maps. Bathymetric and topographic data can also be used to calculate projected surface areas within specified depth/altitude intervals, and constrain the calculation of realistic shortest path distances. Such information can be used in molecular ecology, for example, to evaluate genetic isolation by distance in a spatially-explicit framework.

Gemcitabine and 5-fluorouracil are two commonly used chemotherapeutic agents for the treatment of cancer. François Ghiringhelli and colleagues now report that the antitumor efficacy of these agents is mitigated by myeloid derived suppressor cells (MDSCs). The authors show that these drugs can activate the NLRP3 inflammasome, leading to increased secretion of IL-1β by MDSCs and IL-17 production by CD4 + T cells, which can promote tumor growth. Chemotherapeutic agents are widely used for cancer treatment. In addition to their direct cytotoxic effects, these agents harness the host's immune system, which contributes to their antitumor activity. Here we show that two clinically used chemotherapeutic agents, gemcitabine (Gem) and 5-fluorouracil (5FU), activate the NOD-like receptor family, pyrin domain containing-3 protein (Nlrp3)-dependent caspase-1 activation complex (termed the inflammasome) in myeloid-derived suppressor cells (MDSCs), leading to production of interleukin-1β (IL-1β), which curtails anticancer immunity. Chemotherapy-triggered IL-1β secretion relied on lysosomal permeabilization and the release of cathepsin B, which bound to Nlrp3 and drove caspase-1 activation. MDSC-derived IL-1β induced secretion of IL-17 by CD4 + T cells, which blunted the anticancer efficacy of the chemotherapy. Accordingly, Gem and 5FU exerted higher antitumor effects when tumors were established in Nlrp3 −/− or Casp1 −/− mice or wild-type mice treated with interleukin-1 receptor antagonist (IL-1Ra). Altogether, these results identify how activation of the Nlrp3 inflammasome in MDSCs by 5FU and Gem limits the antitumor efficacy of these chemotherapeutic agents.

Background Placenta Accreta Spectrum Disorders (PASD) are rare but life-threatening obstetric conditions characterized by abnormal placental adherence into or beyond the myometrium, resultant from previous uterine scarring, often rendering placental separation either impossible or associated with a significant risk of massive hemorrhage. As a result, caesarean hysterectomy is commonly performed following delivery, to manage associated complications. With the rising incidence of PASD paralleling the global increase in cesarean deliveries, there is a growing need to investigate and highlight fertility-preserving surgical alternatives. This study aimed to assess the rate of uterine preservation and maternal and fetal outcomes of conservatively managed placenta accreta spectrum disorders (PASD). Methods This retrospective cohort study was performed for conservatively managed patients with PASD at our center between January 2011 and February 2022. Cases were retrieved through operative bookings and codified delivery statistics from the birthing center. Necessary data was then collected through individual chart review. Results Eleven patients underwent conservative management of PASD, of whom eight were delivered by elective caesarean, two by emergency cesarean, and one was an out-born post-partum transfer. A diagnosis of PASD was suspected antenatally in seven of the patients. Seven patients (63.6%) underwent expectant management, with the placenta left in situ, whereas the other four (36.4%) had extirpative or resective management. A total of 8 patients underwent embolization by interventional radiology immediately following their cesarean, and repeat embolization was performed in two patients. Of the 7 patients managed expectantly, three patients had spontaneous resolution of their residual placenta, three patients underwent interval hysterectomy within a range of 24 to 116 days, while the remaining patient required a curettage. The mean time to resolution of patients who underwent expectant management was 83 days. Conclusions In this study, 72.7% of conservatively managed cases of PASD avoided hysterectomy following caesarean delivery. While not without risks, conservative management of PASD can be offered to patients wishing to preserve fertility after individualized counselling.

The development and maintenance of body composition and functions require an adequate protein intake with a continuous supply of amino acids (AA) to tissues. Body pool and AA cellular concentrations are tightly controlled and maintained through AA supply (dietary intake, recycled from proteolysis and de novo synthesis), AA disposal (protein synthesis and other AA-derived molecules) and AA losses (deamination and oxidation). Different molecular regulatory pathways are involved in the control of AA sufficiency including the mechanistic target of rapamycin complex 1, the general control non-derepressible 2/activating transcription factor 4 system or the fibroblast growth factor 21. There is a tight control of protein intake, and human subjects and animals appear capable of detecting and adapting food and protein intake and metabolism in face of foods or diets with different protein contents. A severely protein deficient diet induces lean body mass losses and ingestion of sufficient dietary energy and protein is a prerequisite for body protein synthesis and maintenance of muscle, bone and other lean tissues and functions. Maintaining adequate protein intake with age may help preserve muscle mass and strength but there is an ongoing debate as to the optimal protein intake in older adults. The protein synthesis response to protein intake can also be enhanced by prior completion of resistance exercise but this effect could be somewhat reduced in older compared to young individuals and gain in muscle mass and function due to exercise require regular training over an extended period.

Community trait structure is shaped by environmental filtering and limiting similarity, balancing abiotic selection and competitive divergence. In the context of environmental change and anthropogenic pressures, increasing our understanding of the relative importance of these mechanisms is essential for predicting future changes in biodiversity. The deep-pelagic ecosystem is characterised by pronounced environmental gradients, particularly in light and food availability. The mechanisms by which fish have adapted to these gradients remain poorly understood. To better understand community trait structure, we measured 26 traits related to foraging function in 42 epi- to bathypelagic fish species sampled between 20 and 2000 m depth at night in the Bay of Biscay. We first tested whether limiting similarity or environmental filtering dominates trait structure along the depth gradient by calculating the standardised effect size of four functional diversity indices. Differences in morphological trait values along the depth gradient were then examined using the community weight mean. Species in the epipelagic layer exhibited significant trait convergence, while species in the bathypelagic layer exhibited high functional trait diversity. High locomotor capacity may have been selected in the epipelagic layer, where light and food resources are higher, which could explain the pressure to possess traits adapted for a prey-tracking strategy. In the bathypelagic layer, species may have to limit the competitive pressure for the food-scarce conditions by displaying a higher diversity of feeding strategies. The increase in functional space at depth was supported by a few species with a unique combination of traits that may reflect an ambush hunting strategy. The relatively stable environmental conditions at depth may have favoured high functional diversity and rarity. These results raise concerns about the vulnerability of this community to future climate change and potential exploitation, as rare species may provide irreplaceable functions in ecosystems.

Neuropilins, initially characterized as neuronal receptors, act as co-receptors for cancer related growth factors and were recently involved in several signaling pathways leading to cytoskeletal organization, angiogenesis and cancer progression. Then, we sought to investigate the ability of neuropilin-2 to orchestrate epithelial-mesenchymal transition in colorectal cancer cells. Using specific siRNA to target neuropilin-2 expression, or gene transfer, we first observed that neuropilin-2 expression endows HT29 and Colo320 for xenograft formation. Moreover, neuropilin-2 conferred a fibroblastic-like shape to cancer cells, suggesting an involvement of neuropilin-2 in epithelial-mesenchymal transition. Indeed, the presence of neuropilin-2 in colorectal carcinoma cell lines was correlated with loss of epithelial markers such as cytokeratin-20 and E-cadherin and with acquisition of mesenchymal molecules such as vimentin. Furthermore, we showed by surface plasmon resonance experiments that neuropilin-2 is a receptor for transforming-growth factor-β1. The expression of neuropilin-2 on colon cancer cell lines was indeed shown to promote transforming-growth factor-β1 signaling, leading to a constitutive phosphorylation of the Smad2/3 complex. Treatment with specific TGFβ-type1 receptor kinase inhibitors restored E-cadherin levels and inhibited in part neuropilin-2-induced vimentin expression, suggesting that neuropilin-2 cooperates with TGFβ-type1 receptor to promote epithelial-mesenchymal transition in colorectal cancer cells. Our results suggest a direct role of NRP2 in epithelial-mesenchymal transition and highlight a cross-talk between neuropilin-2 and TGF-β1 signaling to promote cancer progression. These results suggest that neuropilin-2 fulfills all the criteria of a therapeutic target to disrupt multiple oncogenic functions in solid tumors.

Glioblastoma (GBM) is the leading cause of high fatality cancer arising within the adult brain. Electrotherapeutic approaches offer new promise for GBM treatment by exploiting innate vulnerabilities of cancer cells to low intensity electric fields. This report describes the preclinical outcomes of a novel electrotherapeutic strategy called Intratumoral Modulation Therapy (IMT) that uses an implanted stimulation system to deliver sustained, titratable, low intensity electric fields directly across GBM-affected brain regions. This pilot technology was applied to in vitro and animal models demonstrating significant and marked reduction in tumor cell viability and a cumulative impact of concurrent IMT and chemotherapy in GBM. No off target neurological effects were observed in treated subjects. Computational modeling predicted IMT field optimization as a means to further bolster treatment efficacy. This sentinel study provides new support for defining the potential of IMT strategies as part of a more effective multimodality treatment platform for GBM.

In the context of dietary transition toward plant proteins, it is necessary to ensure protein security in populations. It would thus be of interest to identify biomarkers of altered protein digestibility in populations. We examined the association between urinary metabolites and the acute intake of low- or highly digestible protein in healthy volunteers. The urine samples were collected before and 9 h after the ingestion of a meal containing either no protein, zein (low-digestible) or whey protein isolate (highly digestible). The liquid chromatography–high resolution mass spectrometry metabolomics approach was used for the profiling of the urinary metabolites. For the standardization of metabolomics data sets, osmolality-based, standard normal variates (SNV) and probabilistic quotient normalization (PQN) techniques were used. The ANOVA-based factorial method, AComDim_ICA, was used for chemometrics analysis. The osmolality adjustment has a beneficial effect and the subsequent mathematical normalization improves the chemometric analysis further. Some changes in the urinary metabolomes were observed 9 h after the meal in the three groups. However, there was no difference in the urine metabolome between groups. No biomarker of protein digestibility can be identified after the ingestion of a single meal, even when marked differences in the digestion efficiency of protein have been observed.

Environmental conditions can shape genetic and morphological divergence. Release of new habitats during historical environmental changes was a major driver of evolutionary diversification. Here, forces shaping population structure and ecotype differentiation (‘pelagic’ and ‘coastal’) of bottlenose dolphins in the North-east Atlantic were investigated using complementary evolutionary and ecological approaches. Inference of population demographic history using approximate Bayesian computation indicated that coastal populations were likely founded by the Atlantic pelagic population after the Last Glacial Maxima probably as a result of newly available coastal ecological niches. Pelagic dolphins from the Atlantic and the Mediterranean Sea likely diverged during a period of high productivity in the Mediterranean Sea. Genetic differentiation between coastal and pelagic ecotypes may be maintained by niche specializations, as indicated by stable isotope and stomach content analyses, and social behaviour. The two ecotypes were only weakly morphologically segregated in contrast to other parts of the World Ocean. This may be linked to weak contrasts between coastal and pelagic habitats and/or a relatively recent divergence. We suggest that ecological opportunity to specialize is a major driver of genetic and morphological divergence. Combining genetic, ecological and morphological approaches is essential to understanding the population structure of mobile and cryptic species.

A large, but poorly studied, bottlenose dolphin community, Tursiops truncatus, inhabits coastal waters of Normandy (Normano-Breton Gulf, English Channel, France). In this study, the social structure and abundance of this community were assessed using photo-identification techniques. Like other bottlenose dolphin communities worldwide, this resident community has a fission–fusion social structure with fluid associations among individuals (half-weight index = 0.10). Association patterns were highly variable as indicated by a high social differentiation (S = 0.95±0.03). The majority of associations were casual, lasting days to months. However, individuals exhibited also a smaller proportion of long-term relationships. A mean group size of 26 was large compared with other resident coastal communities, and variable, ranging from 1 to 100, which could be the results of ecological conditions, in particular resource predictability and availability. Analyses also showed that the community was organized in 3 social clusters that were not completely isolated from each other. Abundance was estimated at 420 dolphins (95% confidence interval: 331–521), making this coastal community one of the largest identified along European coastlines. Because human activities in the Gulf are expected to increase in the upcoming years, long-term demographic monitoring of this dolphin community will be critical for its management.