Search

Abstract Nontransformed cells form heterotypic cadherin junctions with adjacent transformed cells to inhibit tumor cell growth and motility. Transformed cells must override this form of growth control, called “contact normalization”, to invade and metastasize during cancer progression. Heterocellular cadherin junctions between transformed and nontransformed cells are needed for this process. However, specific mechanisms downstream of cadherin signaling have not been clearly elucidated. Here, we utilized a β-catenin reporter construct to determine if contact normalization affects Wnt signaling in transformed cells. β-catenin driven GFP expression in Src transformed mouse embryonic cells was decreased when cultured with cadherin competent nontransformed cells compared to transformed cells cultured with themselves, but not when cultured with cadherin deficient nontransformed cells. We also utilized a layered culture system to investigate the effects of oncogenic transformation and contact normalization on gene expression and oncogenic Src kinase mediated phosphorylation events. RNA-Seq analysis found that cadherin dependent contact normalization inhibited the expression of 22 transcripts that were induced by Src transformation, and increased the expression of 78 transcripts that were suppressed by Src transformation. Phosphoproteomic analysis of cells expressing a temperature sensitive Src kinase construct found that contact normalization decreased phosphorylation of 10 proteins on tyrosine residues that were phosphorylated within 1 h of Src kinase activation in transformed cells. Taken together, these results indicate that cadherin dependent contact normalization inhibits Wnt signaling to regulate oncogenic kinase activity and gene expression, particularly PDPN expression, in transformed cells in order to control tumor progression.

The data presented in this paper include the original and processed MRI images acquired with a 1.5 T whole-body MRI scanner, describing the growth kinetics, spatialization and appearance of internal defaults of individual tubers of potato plants (Rosanna cultivar of Solanum tuberosum) grown in pots in a semi-controlled environment and exposed to two water regimes. The 2 conditions were a well-watered regime, in which soil moisture was maintained at 70 % of field capacity, and a variable water deficit regime, in which soil moisture was reduced to 20 % of field capacity several times during tuber growth, followed each time by a few-day period of rehydration to 70 % of field capacity. These data are supplemented by physiological, biochemical and gene expression data obtained from the leaves and tubers of additional potato plants grown under the same conditions. All these data contribute to highlight the long-term effects of water stress on plant functioning with a particular focus on the growth kinetics, spatialization and quality of potato tubers. The dataset presented here is related to the research article entitled “Growth kinetics, spatialization and quality of potato tubers monitored in situ by MRI - long-term effects of water stress”. It is made publicly available to enable extended analyzes. It is a useful resource for biologists, agronomists and breeders interested in the potato crop, as well as for researchers interested in developing new imaging methods. All data can be used to improve databases on development and quality of tubers and to feed and validate mathematical models.

Most of our knowledge of past seawater temperature history is based on δ18O values of calcium carbonate fossil shells. However, the determination of past temperatures using this proxy requires the knowledge of past seawater δ18O values, which is generally poorly constrained. Other paleothermometers using carbonate archives, such as Mg/Ca ratios and clumped isotopes (Δ47), have been developed to allow for paleotemperatures to be estimated independently and to allow past ocean δ18O values to be calculated using various groups of calcifying organisms. Articulated brachiopod shells are some of the most commonly used archives in studies of past oceanic geochemistry and temperature. They are abundant in the fossil record since the Cambrian, and for decades, their low Mg–calcite mineralogy has been considered relatively resistant to diagenetic alteration. Here, we investigate the potential of brachiopod shells as recorders of seawater temperatures and seawater δ18O values using new brachiopod shell geochemical data by testing multiple well-established or suggested paleothermometers applied to carbonate archives. Modern articulated brachiopod shells covering a wide range of temperatures (−1.9 to 25.5 ∘C), depths (5 to 3431 m) and salinities (33.4 to 37.0 PSU) were analysed for their stable isotope compositions (δ13C, δ18O and Δ47) and their elemental ratios (Mg/Ca, Sr/Ca, Na/Ca and Li/Ca). Our data allowed us to propose a revised oxygen isotope fractionation equation between modern-brachiopod shell calcite and seawater: (1) T = - 5.0 ( ± 0.2 ) ( δ 18 O c - δ 18 O sw ) + 19.4 ( ± 0.4 ) , where δ18Oc is in ‰ VPDB, δ18Osw is in ‰ VSMOW, and T is in ∘C. Our results strongly support the use of clumped isotopes as an alternative temperature proxy but confirm significant offsets relative to the canonical relationship established for other biogenic and abiogenic calcium carbonate minerals. Brachiopod shell Mg/Ca ratios show no relationship with seawater temperatures, indicating that this ratio is a poor recorder of past changes in temperatures, an observation at variance with several previous studies. Despite significant correlations with brachiopod living temperature, brachiopod shell Sr/Ca, Na/Ca and Li/Ca values indicate the influence of environmental and biological factors unrelated to temperature, which undermines their potential as alternative temperature proxies. Kinetic effects (growth rates) could explain most of the deviation of brachiopod shell calcite from expected isotopic equilibrium with seawater and part of the distribution of Sr/Ca, Na/Ca and Li/Ca ratios.

Abstract Background Equine strongyles encompass more than 64 species of nematode worms that are responsible for growth retardation and the death of animals. The factors underpinning variation in the structure of the equine strongyle community remain unknown. Methods Using horse-based strongyle community data collected after horse deworming (48 horses in Poland, 197 horses in Ukraine), we regressed species richness and the Gini-Simpson index upon the horse’s age, faecal egg count, sex and operation of origin. Using the Ukrainian observations, we applied a hierarchical diversity partitioning framework to estimate how communities were remodelled across operations, age groups and horses. Lastly, strongyle species counts collected after necropsy (46 horses in France, 150 in Australia) were considered for analysis of their co-occurrences across intestinal compartments using a joint species distribution modelling approach. Results First, inter-operation variation accounted for > 45% of the variance in species richness or the Gini-Simpson index (which relates to species dominance in communities). Species richness decreased with horse’s age (P = 0.01) and showed a mild increase with parasite egg excretion (P

From 2014 to 2021 during the cyclone seasons, extensive monitoring of the hydrodynamics within a variety of lagoons of New Caledonia was conducted as a part of the PRESENCE project (PRESsures on coral Ecosystems of New CalEdonia). The PRESENCE project is aimed at building an efficient representation of the land–lagoon–ocean continuum at Grande Terre, New Caledonia's main island. Overall, coastal physical observations encompassed five different lagoons (four of which were never before monitored) and at least eight major atmospheric events ranging from tropical depressions to category 4 cyclones. The main objectives of this study were to characterize the processes controlling the hydrodynamics and hydrology of these lagoons (e.g., ocean–lagoon exchanges, circulation, level dynamics, temperature, and salinity variability), and to capture the magnitude of change during extreme events. An additional objective was to compile an adequate data set for future use in high-resolution hydrodynamic models. Autonomous oceanographic instruments were moored at strategic locations to collect time series of temperature, salinity, pressure, and Eulerian currents. Additionally, Lagrangian surface currents were observed through deploying drifter buoys, and cross-shore hydrological profile radials were carried out using CTDs (conductivity, temperature, depth). In total, five survey campaigns were conducted, beginning with the SPHYNX campaign which lasted 15 months (December 2014 to February 2016) in the Hienghène–Touho lagoon and ended with the 9 months NEMO campaign (September 2020 to April 2021) in Moindou lagoon. Between these were the 5 months NOUMEA campaign (December 2016 to April 2017) in Noumea lagoon, the 6 months ELADE campaign (February to August 2018) in the Poe lagoon, and the 5 months CADHYAK campaign (December 2019 to May 2020) in Koumac lagoon. In addition to characterizing these lagoons, the data set identifies important features and processes, such as the presence of internal waves on forereefs, wave-driven fluxes over reef barriers, and exchanges through passes. Signatures from strong events were also identified, including surges, thermal drops inside lagoons, and massive flash flood plume dispersion. Raw data sets were processed, controlled for quality, validated, and analyzed. Processed files are made publicly available in dedicated repositories on the SEANOE marine data platform in NetCDF format. Links (DOI) of individual data sets are provided herein.

In J. L. Austin’s works, the idea that language is action is certainly not new. What is however more important for us today is how the introduction of the idea of speech acts transforms not only the conception of language, but also the conception of action: it indeed weakens both our understanding of the notions of “meaning” and of “action”. In Austin’s work, it is the triplet “speech act”/“failure”/“excuse” that is central, and the articulation of these three elements makes obvious the essential character of the social dimension of action in his philosophy. While this article is certainly not a historical study in ethnomethodology, it is yet undoubtedly guided by the idea of sociological enquiry inherited from Harold Garfinkel, where the social order is not an independent reality, and where one seeks to elucidate the constant making of it, as it is recognizable, intelligible, analyzable and reportable by the participants.

Background: Despite current recommendation, vaccination coverage (VC) for patients with heart failure (HF) remains far too limited. Aims: To evaluate the VC of HF patients followed in our hospital center and investigate the barriers to vaccination and the ways to address them. Methods: This was a cross-sectional monocentric descriptive study conducted between December 2019 and January 2021 at the University Hospital of Montpellier, France. Patients with HF history hospitalized in cardiology unit (CU) and patients in a HF telemonitoring program (TP) were included. An interview was conducted by a pharmacist to find out the patient's vaccination status against influenza and pneumococcus. For non-vaccinated patients, opinion and willingness to be vaccinated were also obtained. Results: Data from 335 patients were collected (185 in CU, 150 in TP). The mean age was 69.3 years and the proportion of males was 72%. About 65% were vaccinated against influenza in the last year (60% in CU, 72% in TP, p = 0.022) and 22% were up to date with pneumococcal vaccination (11% in CU, 35% in TP, p

New words have found their way into the public sphere: we now commonly talk about “confinement”, “barrier-gesture” or “distancing”. The very idea of public space has been transformed: with restrictions on movement and interaction in public; with the reintegration of lives (certain lives) into the home (if there is one) and private space; with the publicization of private space through internet relationships; with the cities’ space occupied, during confinement, by so-called “essential” workers; with the restriction of gatherings and political demonstrations in public space. With these and other recent changes, it is imperative to revisit the concept of public space, which continues to be used as if it were self-evident, despite its profound transformation over the past few decades, in a process of realization and “literalization”. No longer just a comfortable metaphor for reasonable debates, public space has become a concrete reality in the 21th century. This transformation in the various phenomena, such as the occupation of squares and public spaces; the demand for spaces of conversation and expression for those without a voice; the transition of private matters into the public realm through verbal expression; and the expression and circulation of public issues within popular cultures. As a result, the question of public space is increasingly intertwined with that of private spaces, such as the home or individual subjectivities, forming an internal, logical relationship.

We resolve the multiple images of the binary-lens microlensing event ASASSN-22av using the GRAVITY instrument of the Very Large Telescope Interferometer (VLTI). The light curves show weak binary-lens perturbations, complicating the analysis, but the joint modeling with the VLTI data breaks several degeneracies, arriving at a strongly favored solution. Thanks to precise measurements of the angular Einstein radius θ _E = 0.724 ± 0.002 mas and microlens parallax, we determine that the lens system consists of two M dwarfs with masses of M _1 = 0.258 ± 0.008 M _⊙ and M _2 = 0.130 ± 0.007 M _⊙ , a projected separation of r _⊥ = 6.83 ± 0.31 au, and a distance of D _L = 2.29 ± 0.08 kpc. The successful VLTI observations of ASASSN-22av open up a new path for studying intermediate-separation (i.e., a few astronomical units) stellar-mass binaries, including those containing dark compact objects such as neutron stars and stellar-mass black holes.

This paper summarized the efforts performed to understand decay heat estimation from existing spent nuclear fuel (SNF), under the auspices of the Working Party on Nuclear Criticality Safety (WPNCS) of the OECD Nuclear Energy Agency. Needs for precise estimations are related to safety, cost, and optimization of SNF handling, storage, and repository. The physical origins of decay heat (a more correct denomination would be decay power) are then introduced, to identify its main contributors (fission products and actinides) and time-dependent evolution. Due to limited absolute prediction capabilities, experimental information is crucial; measurement facilities and methods are then presented, highlighting both their relevance and our need for maintaining the unique current full-scale facility and developing new ones. The third part of this report is dedicated to the computational aspect of the decay heat estimation: calculation methods, codes, and validation. Different approaches and implementations currently exist for these three aspects, directly impacting our capabilities to predict decay heat and to inform decision-makers. Finally, recommendations from the expert community are proposed, potentially guiding future experimental and computational developments. One of the most important outcomes of this work is the consensus among participants on the need to reduce biases and uncertainties for the estimated SNF decay heat. If it is agreed that uncertainties (being one standard deviation) are on average small (less than a few percent), they still substantially impact various applications when one needs to consider up to three standard deviations, thus covering more than 95% of cases. The second main finding is the need of new decay heat measurements and validation for cases corresponding to more modern fuel characteristics: higher initial enrichment, higher average burnup, as well as shorter and longer cooling time. Similar needs exist for fuel types without public experimental data, such as MOX, VVER, or CANDU fuels. A third outcome is related to SNF assemblies for which no direct validation can be performed, representing the vast majority of cases (due to the large number of SNF assemblies currently stored, or too short or too long cooling periods of interest). A few solutions are possible, depending on the application. For the final repository, systematic measurements of quantities related to decay heat can be performed, such as neutron or gamma emission. This would provide indications of the SNF decay heat at the time of encapsulation. For other applications (short- or long-term cooling), the community would benefit from applying consistent and accepted recommendations on calculation methods, for both decay heat and uncertainties. This would improve the understanding of the results and make comparisons easier.

Directly observing exoplanets with coronagraphs is impeded by the presence of speckles from aberrations in the optical path, which can be mitigated in hardware with wave front control, as well as in post-processing. This work explores using an instrument model in post-processing to separate astrophysical signals from residual aberrations in coronagraphic data. The effect of wave front error (WFE) on the coronagraphic intensity consists of a linear contribution and a quadratic contribution. When either of the terms is much larger than the other, the instrument response can be approximated by a transfer matrix mapping WFE to detector plane intensity. From this transfer matrix, a useful projection onto instrumental modes that removes the dominant error modes can be derived. We apply this approach to synthetically generated Roman Space Telescope hybrid Lyot coronagraph data to extract “robust observables,” which can be used instead of raw data for applications such as detection testing. The projection improves planet flux ratio detection limits by about 28% in the linear regime and by over a factor of 2 in the quadratic regime, illustrating that robust observables can increase sensitivity to astrophysical signals and improve the scientific yield from coronagraphic data. While this approach does not require additional information such as observations of reference stars or modulations of a deformable mirror, it can and should be combined with these other techniques, acting as a model-informed prior in an overall post-processing strategy.

Stanley Cavell was the first to account for the transformation of theory and criticism brought about by reflection on popular culture and its 'ordinary' objects, such as so-called mainstream cinema. However, Cavell is less concerned with reversing artistic hierarchies than with the self-transformation required by our encounters with new experiences, and with the moral education they provide. According to him the value of a culture lies not in its 'great art' but in its transformative capacity, the same capacity found in Emerson's 'moral perfectionism'. This new accent on examining the educational value of films as public occurrences of ethical theorising points towards the analysis of linguistic and aesthetic expression in a larger corpus works of 'popular culture', hence to going beyond Cavell's focus on the classical Hollywood movie.

Abstract Submarine fan deposits are volumetrically the largest sediment accumulations on Earth and host significant hydrocarbon reserves. Extensive research has documented the bed‐scale architecture of high sand‐to‐mud ratio, proximal and axial environments, which can have bed thicknesses of several metres; however, less well‐understood are thin‐bedded turbidites, which are typically lower N:G and deposited in more distal environments. Conceptual models assume that lobe‐fringe‐to‐basin plain environments consist of tabular, sheet‐like beds that extend out continuously and predictably over long distances—up to several kilometres. Extensive lateral continuity, however, is not necessarily reflected in ancient outcrop analogues. This study seeks to apply a quantitative approach to the characterisation of thin‐bedded turbidites to assess the impact of multi‐scale heterogeneity on reservoir predictability. The sea‐cliff outcrop exposures of the Upper Cretaceous Point Loma Formation in San Diego, California, exhibit a wide range of bed thicknesses and stratigraphic architecture, which have been used to interpret an off‐axis‐to‐fringe depositional environment. The study area spans 700 m of laterally continuous outcrop, across which 10 correlated stratigraphic sections are used to quantify changes in metrics such as bed thickness, N:G, lithofacies proportions, etc. Results of this study demonstrate that thin sand beds experience both lateral facies changes and rapid thickness changes more frequently than conceptual models would predict. A single measure of lateral heterogeneity does not reflect the true architecture of sandstone beds, and significant information is lost when beds are correlated over ten to hundreds of metres. Sands are commonly deposited in irregular, ‘finger‐like’, planform geometries, which compounds at the lobe element scale and influences lateral lithofacies predictability. This study of the Point Loma Formation offers high‐resolution bed‐to‐element scale data, which may be used as inputs for reservoir models and horizontal facies predictions in both conventional and unconventional hydrocarbon reservoirs.

Strategies used by marine vertebrates to regulate their body temperature can result in local variations, and the knowledge of these regional heterothermies is crucial for better understanding the thermophysiologies of extant and extinct organisms. In order to investigate regional heterothermies in vertebrates, we analysed the oxygen isotope composition of phosphatic skeletal elements (δ18Op) of two endothermic fishes (Thunnus thynnus and Xiphias gladius) and three dolphins (two Delphinus delphis delphis and one Cephalorhynchus commersonii kerguelensis). We observed a consistent link between δ18Op variations and temperature heterogeneities recorded by classical methods. Our δ18Op data indicate that: (i) bone hydroxylapatite of the axial skeleton of dolphins mineralise at a warmer temperature than that of the appendicular one, (ii) the skull is the warmest body region in X. gladius, and (iii) T. thynnus possesses high body temperature in the skull and visceral mass region. These results demonstrate the possibility of tracking regional heterothermies in extant marine vertebrates using the δ18Op, paving the way to direct assessment of thermophysiological specificities of both living and extinct vertebrates. From a palaeoenvironmental perspective, the significant observed δ18Op variability questions the use of some taxa or random skeletal elements for the reconstruction of palaeoceanographic parameters such as seawater temperature and δ18O.

Periods of high atmospheric CO2 levels during the Cretaceous–early Paleogene (∼ 140 to 34 Myr ago) were marked by very high polar temperatures and reduced latitudinal gradients relative to the Holocene. These features represent a challenge for most climate models, implying either higher-than-predicted climate sensitivity to atmospheric CO2 or systematic biases or misinterpretations in proxy data. Here, we present a reconstruction of marine temperatures at polar (> 80∘) and middle (∼ 40∘) paleolatitudes during the Early Jurassic (∼ 180 Myr ago) based on the clumped isotope (Δ47) and oxygen isotope (δ18Oc) analyses of shallow buried pristine mollusc shells. Reconstructed calcification temperatures range from ∼ 8 to ∼ 18 ∘C in the Toarcian Arctic and from ∼ 24 to ∼ 28 ∘C in Pliensbachian mid-paleolatitudes. These polar temperatures were ∼ 10–20 ∘C higher than present along with reduced latitudinal gradients. Reconstructed seawater oxygen isotope values (δ18Ow) of −1.5 ‰ to 0.5 ‰ VSMOW and of −5 ‰ to −2.5 ‰ VSMOW at middle and polar paleolatitudes, respectively, point to a significant freshwater contribution in Arctic regions. These data highlight the risk of assuming the same δ18Osw value for δ18O-derived temperature from different oceanic regions. These findings provide critical new constraints for model simulations of Jurassic temperatures and δ18Osw values and suggest that high climate sensitivity has been a hallmark of greenhouse climates for at least 180 Myr.

Abstract Multi-cropping was vital for provisioning large population centers across ancient Eurasia. In Southwest Asia, multi-cropping, in which grain, fodder, or forage could be reliably cultivated during dry summer months, only became possible with the translocation of summer grains, like millet, from Africa and East Asia. Despite some textual sources suggesting millet cultivation as early as the third millennium BCE, the absence of robust archaeobotanical evidence for millet in semi-arid Mesopotamia (ancient Iraq) has led most archaeologists to conclude that millet was only grown in the region after the mid-first millennium BCE introduction of massive, state-sponsored irrigation systems. Here, we present the earliest micro-botanical evidence of the summer grain broomcorn millet (Panicum miliaceum) in Mesopotamia, identified using phytoliths in dung-rich sediments from Khani Masi, a mid-second millennium BCE site located in northern Iraq. Taphonomic factors associated with the region’s agro-pastoral systems have likely made millet challenging to recognize using conventional macrobotanical analyses, and millet may therefore have been more widespread and cultivated much earlier in Mesopotamia than is currently recognized. The evidence for pastoral-related multi-cropping in Bronze Age Mesopotamia provides an antecedent to first millennium BCE agricultural intensification and ties Mesopotamia into our rapidly evolving understanding of early Eurasian food globalization.

Lockdown has given us an occasion to discover new television series and to revisit others. TV series accompany us in our ordinary lives, but they can also be a resource or refuge in extraordinary situations. As the enduring success of Friends proves, they provide us with universes of comfort. TV series provide strong common cultural referents, which populate both ordinary conversations and political debates. TV series, by virtue of their aesthetic format (their duration, weekly and seasonal regularity, and the fact that they are, or were until recently, usually viewed in the context of the home), the attachment they inspire to their characters, the democratization and diversification of modes of viewing them (internet, streaming, discussion forums), make possible a specific form of education and constitution of a public. TV shows are hence a medium for political and ethical discussion. The article studies two series, Homeland and The Bureau, which are paradigmatic examples of a genre that has grown exponentially since the beginning of the century, and which we refer to as the “security series” genre. These series are great works of art and can also be seen as powerful tools for educating and informing the public.

Introduction to Special Issue

Abstract Over the last several years, numerous outcrop localities have been revisited to add quantitative detail to submarine lobe facies models that previously focussed on facies relationships in a qualitative sense. This study utilises well‐exposed submarine lobe deposits of the Point Loma Formation in Cabrillo National Monument (San Diego, CA) to provide quantitative and statistical insights into the lateral variability of event‐bed (i.e. turbidite) architecture within and between lobe elements. Within a lobe element (defined as a surface‐bounded, genetically related package), event beds compensationally stack, thinning over subtle sea floor topography created by the previous event bed. Between lobe elements, larger‐scale compensation is observed, with clearly defined stratal surfaces and facies architecture distinguishing the four lobe elements. A lateral facies transition is observed for one lobe element, where sandstone beds pinch out and the element thickness halves over a distance of 100 m. However, architectural parameters of event beds (e.g. bed thickness, thinning rate, fining rate) are not appreciably different between these elements, suggesting that the observed stratal architecture does not readily translate into vertical bed thickness (i.e. stacking) patterns that could be easily recognised in common subsurface data types like borehole‐derived core. While the data derived from this outcrop study are valuable for improving the construction of realistic geological and reservoir models, caution is necessary when interpreting lobe element boundaries from borehole data. The lobe deposits measured in this study have event‐bed thicknesses and thinning rates most similar to semi‐confined proximal lobes, suggesting a more proximal position and more confined than previously interpreted. Based on the relationships between sandstone and mudstone thicknesses and thinning rates, bed and lobe‐element compensation and minimal evidence of erosion, the Point Loma Formation at Cabrillo National Monument is reinterpreted as a medial lobe environment with some degree of lateral and/or frontal confinement.

Measurement(s) plant trait Technology Type(s) digital curation Sample Characteristic - Organism Viridiplantae Sample Characteristic - Location Australia Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.14545755

Chagas disease, caused by the protozoan Trypanosoma cruzi, is an endemic parasitic disease of Latin America, affecting 7 million people. Although most patients are asymptomatic, 30% develop complications, including the often-fatal Chronic Chagasic Cardiomyopathy (CCC). Although previous studies have demonstrated some genetic deregulations associated with CCCs, the causes of their deregulations remain poorly described. Based on bulk RNA-seq and whole genome DNA methylation data, we investigated the genetic and epigenetic deregulations present in the moderate and severe stages of CCC. Analysis of heart tissue gene expression profile allowed us to identify 1407 differentially expressed transcripts (DEGs) specific from CCC patients. A tissue DNA methylation analysis done on the same tissue has permitted the identification of 92 regulatory Differentially Methylated Regions (DMR) localized in the promoter of DEGs. An in-depth study of the transcription factors binding sites (TFBS) in the DMRs corroborated the importance of TFBS’s DNA methylation for gene expression in CCC myocardium. TBX21, RUNX3 and EBF1 are the transcription factors whose binding motif appears to be affected by DNA methylation in the largest number of genes. By combining both transcriptomic and methylomic analysis on heart tissue, and methylomic analysis on blood, 4 biological processes affected by severe CCC have been identified, including immune response, ion transport, cardiac muscle processes and nervous system. An additional study on blood methylation of moderate CCC samples put forward the importance of ion transport and nervous system in the development of the disease.

Objectives: Study of the rifampicin resistance of Rhodococcus equi strains isolated from French horses over a 20-year period. Methods: Rifampicin susceptibility was tested by disk diffusion (DD) and broth macrodilution methods, and rpoB gene sequencing and MLST were performed on 40 R. equi strains, 50.0% of which were non-susceptible to rifampicin. Results: Consistency of results was observed between rifampicin susceptibility testing and rpoB sequencing. Strains non-susceptible to rifampicin by DD had a substitution at one of the sites (Asp516, His526 and Ser531) frequently encountered and conferring rifampicin resistance. High-level resistance was correlated with His526Asp or Ser531Leu substitutions; low-level resistance was correlated with Asp516Tyr substitution, a novel substitution for R. equi. Strains susceptible to rifampicin by DD showed no substitution in the three sites, except for two strains carrying, respectively, the His526Asn and Asp516Val substitutions (previously correlated with low-level rifampicin resistance). Both strains were isolated from an animal from which ten other strains were also isolated and found to be rifampicin-non-susceptible by DD. MLST showed the presence of 10 STs (including the novel ST43), but no association was observed with rifampicin resistance. Conclusions: This study confirms that certain substitutions in RpoB are more likely to confer high- or low-level rifampicin resistance, describes a new substitution conferring rifampicin resistance in R. equi and suggests non-clonal dissemination of rifampicin-resistant strains in France. Standard DD may miss strains with a low-level rifampicin-resistant substitution; further studies are needed to remedy the absence of R. equi-specific clinical breakpoints.

Today, the satellite-based monitoring of archaeological sites and site damage is a widespread practice, especially in conflict-affected regions. However, the vast majority of these remote sensing cultural heritage monitoring efforts have been led and conducted by remote researchers, and there remains an urgent need to embed this work within existing, in-country institutions at local and regional levels. Here, we present the archaeological site monitoring approach and results from the project Archaeological Practice and Heritage Protection in the Kurdistan Region of Iraq, a collaborative project between the Sirwan Regional Project and Kurdish Iraqi archaeologists aimed at generating a fully functional and sustainable programme of archaeological site management co-created with, and managed by, Kurdish Iraqi archaeologists and antiquities officials. Between August 2018 and February 2020, 376 archaeological sites in the Sirwan/Upper Diyala River Valley region, located in the Kurdistan Region of Iraq, were assessed for damage by Kurdish Iraqi archaeologists in collaboration with the Sirwan Regional Project. This work represents the first large-scale, systematic dataset of archaeological site conditions and longer-term damage in the Kurdistan Region of Iraq (KRI). Our results show that 86.7% of the assessed archaeological sites and 38.6% of the site surface area in this region were affected by damage between 1951-2018, and demonstrate the great urgency with which action must be taken to develop appropriate safeguarding measures for the KRI's archaeological heritage. On the basis of these results, we outline relevant recommendations for the immediate protection of archaeological sites in Garmian and the greater Kurdistan Region.

Photonic technologies offer numerous functionalities that can be used to realize astrophotonic instruments. The most spectacular example to date is the ESO Gravity instrument at the Very Large Telescope in Chile that combines the light-gathering power of four 8 m telescopes through a complex photonic interferometer. Fully integrated astrophotonic devices stand to offer critical advantages for instrument development, including extreme miniaturization when operating at the diffraction-limit, as well as integration, superior thermal and mechanical stabilization owing to the small footprint, and high replicability offering significant cost savings. Numerous astrophotonic technologies have been developed to address shortcomings of conventional instruments to date, including for example the development of photonic lanterns to convert from multimode inputs to single mode outputs, complex aperiodic fiber Bragg gratings to filter OH emission from the atmosphere, complex beam combiners to enable long baseline interferometry with for example, ESO Gravity, and laser frequency combs for high precision spectral calibration of spectrometers. Despite these successes, the facility implementation of photonic solutions in astronomical instrumentation is currently limited because of (1) low throughputs from coupling to fibers, coupling fibers to chips, propagation and bend losses, device losses, etc, (2) difficulties with scaling to large channel count devices needed for large bandwidths and high resolutions, and (3) efficient integration of photonics with detectors, to name a few. In this roadmap, we identify 24 key areas that need further development. We outline the challenges and advances needed across those areas covering design tools, simulation capabilities, fabrication processes, the need for entirely new components, integration and hybridization and the characterization of devices. To realize these advances the astrophotonics community will have to work cooperatively with industrial partners who have more advanced manufacturing capabilities. With the advances described herein, multi-functional integrated instruments will be realized leading to novel observing capabilities for both ground and space based platforms, enabling new scientific studies and discoveries.

It may be time to question analytic philosophy’s structural ignorance of the methods of ordinary language philosophy. Cavell’s Must We Mean What We Say? upsets the analytic tradition to this end, pursuing a “linguistic phenomenology” that focuses on ordinary language use as a resource for describing the world. Cavell thereby entrusts the tradition with a more ambitious and concrete philosophical task.

This paper aims to bring together the appeal to the ordinary in the ethics of care and the ‘destruction’ or philosophical subversion which Wittgenstein references in his Philosophical Investigations: Where does our investigation get its importance from, since it seems to destroy everything interesting, all that is great and important? What we are destroying is nothing but houses of cards. The paper pursues a connection between the ethics of care and ordinary language philosophy as represented by Wittgenstein, Austin and Cavell, in particular in a feminist perspective. The central point of Carol Gilligan’s In a Different Voice may not be the idea of a ‘feminine morality’ but a claim for an alternative form of morality. Gilligan’s essay seeks to capture a different, hitherto neglected yet universally present alternative ethical perspective, one easy to ignore because it relates to women and women’s activities. The ethics of care recalls a plea for ‘realism’; in the sense given to it in Cora Diamond’s The Realistic Spirit to mean the necessity of seeing (or attending to) what lies close at hand. Reflection on care brings ethics back to everyday practice much as Wittgenstein sought to bring language back from the metaphysical level to its everyday use.

This introductive article propose a brief overview of the contributions of Stanley Cavell in his dialogues between philosophy and cinema. It emphasizes the rock of the ordinary (in the wake of Emerson, Thoreau, Wittgenstein and Austin), the links between moral perfectionism and democratic radicality, its educational and self-educational scope, as well as the importance of considering ordinary cultures (cinema, TV series, etc.) as true democratic arts. It then sketches out what some of the axes of a Cavellian-inspired program could be for the study of TV series in philosophy and social sciences. Finally, it presents the various contributions of this issue of TV/Series devoted to “Perfectionism and TV series. A tribute to Stanley Cavell (1926-2018)”.

Chronic Chagas disease cardiomyopathy (CCC), an especially aggressive inflammatory dilated cardiomyopathy caused by lifelong infection with the protozoan Trypanosoma cruzi, is a major cause of cardiomyopathy in Latin America. Although chronic myocarditis may play a major pathogenetic role, little is known about the molecular mechanisms responsible for its severity. The aim of this study is to study the genes and microRNAs expression in tissues and their connections in regards to the pathobiological processes. To do so, we integrated for the first time global microRNA and mRNA expression profiling from myocardial tissue of CCC patients employing pathways and network analyses. We observed an enrichment in biological processes and pathways associated with the immune response and metabolism. IFNγ, TNF and NFkB were the top upstream regulators. The intersections between differentially expressed microRNAs and differentially expressed target mRNAs showed an enrichment in biological processes such as Inflammation, inflammation, Th1/IFN-γ-inducible genes, fibrosis, hypertrophy, and mitochondrial/oxidative stress/antioxidant response. MicroRNAs also played a role in the regulation of gene expression involved in the key cardiomyopathy-related processes fibrosis, hypertrophy, myocarditis and arrhythmia. Significantly, a discrete number of differentially expressed microRNAs targeted a high number of differentially expressed mRNAs (>20) in multiple processes. Our results suggest that miRNAs orchestrate expression of multiple genes in the major pathophysiological processes in CCC heart tissue. This may have a bearing on pathogenesis, biomarkers and therapy.

Il évoque à la fois la lourdeur des choses, mais ne se pèse pas. Il est à la fois très complet, mais sonne comme sonne le vide. Il ne recense aucun mot, mais c'est bien un langage. Le silence, voilà un terme si injuste, si vague... Quelque part, le silence, c'est l’ennemi même de notre société. Mais c’est aussi la clé d’une dictature ; c’est une bouche qui se ferme, un être qui se tait, qui n’a plus le moyen de refléter sa pensée. Et ce n’est pas un hasard si l’Homme se voit, selon l'expression et dans la plupart des cas, puisque chaque personne devrait avoir accès à la liberté de parole, “contraint au silence”. Une contrainte, donc, voici ce qu’est le silence à nos yeux. Mais selon le point de vue le silence, c’est un dû, un renfermement sur soi-même, certes, mais qui sait aussi fixer les limites de la parole. C’est une bulle qui nous permet de garder une partie de notre existence et de nos actes privés. Les réseaux sociaux, les connexions en continu, les prises de parole archivées, retranscrites en temps et en heure, par le moyen de la radio, de la télévision, sont des avancées claires et nettes dans l’Histoire de l’Humanité. Néanmoins, elles représentent aussi une violation de nos droits fondamentaux. Le silence appelle à la sagesse de l’Homme, à ne pas trop s’exprimer, car cela pourrait se retourner contre lui. Après tout, “la parole est d’argent, le silence est d’or”.

Constraining the avulsion dynamics of rivers and submarine channels is essential for predicting the distribution of sediment, organic matter, and pollutants in alluvial, deltaic, and submarine settings. We create a geometric channel-belt framework relating channel, levee, and floodplain stratigraphy that allows comparative analysis of avulsion dynamics for rivers and submarine channels. We utilize 52 channel-overbank cross-sections within this framework to provide avulsion criteria for submarine channels, and how they differ from rivers. Superelevation and a new channel-floodplain coupling metric are two key parameters that control channel-belt thickness in both rivers and submarine channels. While rivers only superelevate 1 channel depth above the floodplain prior to avulsion, submarine channels are more stable during aggradation, with superelevation values commonly > 3 channel depths. Additionally, channel-floodplain coupling in rivers is often weak, with floodplain aggradation negligible compared to channel aggradation, making rivers avulsion-prone. However, floodplain aggradation is more significant for submarine channels, resulting in stronger channel-floodplain coupling and thus a decreased potential for avulsion. The combination of enhanced superelevation and strong channel-floodplain coupling results in submarine channel-belts that can be as thick as ∼10 channel depths, while fluvial channel belts are limited to 2 channel depths. Submarine channels are more stable because turbidity currents have ∼50x lower density contrast between flow and ambient fluid as compared to rivers. This density contrast creates far less potential energy for avulsion, despite the much greater relief of submarine levees compared to fluvial levees. The modern Amazon submarine channel showcases this stability, with a channel belt that is ∼5 channel-depths thick for more than 400 streamwise km, which is more than twice the superelevation that a river is capable of. We interpret that enhanced floodplain aggradation and levee aggradation (and thus superelevation) in submarine channel belts are promoted by unique submarine flow characteristics, including turbidity current overspill, flow-stripping, and hemipelagic processes. We emphasize that rivers and submarine channels display very different avulsion dynamics and frequencies, profoundly affecting the stratigraphic architecture of channel-belt and downstream distributary deposits.

Despite improvements in donor screening and increasing efforts to avoid contamination and the spread of pathogens in clinical platelet concentrates (PCs), the risks of transfusion-transmitted infections remain important. Relying on an ultraviolet photo activation system, pathogen reduction technologies (PRTs), such as Intercept and Mirasol, utilize amotosalen, and riboflavin (vitamin B2), respectively, to mediate inactivation of pathogen nucleic acids. Although they are expected to increase the safety and prolong the shelf life of clinical PCs, these PRTs might affect the quality and function of platelets, as recently reported. Upon activation, platelets release microparticles (MPs), which are involved in intercellular communications and regulation of gene expression, thereby mediating critical cellular functions. Here, we have used small RNA sequencing (RNA-Seq) to document the effect of PRT treatment on the microRNA profiles of platelets and derived MPs. PRT treatment did not affect the microRNA profile of platelets. However, we observed a specific loading of certain microRNAs into platelet MPs, which was impaired by treatment with Intercept or its Additive solution (SSP+). Whereas, Intercept had an impact on the microRNA profile of platelet-derived MPs, Mirasol did not impact the microRNA profile of platelets and derived MPs, compared to non-treated control. Considering that platelet MPs are able to transfer their microRNA content to recipient cells, and that this content may exert biological activities, those findings suggest that PRT treatment of clinical PCs may modify the bioactivity of the platelets and MPs to be transfused and argue for further investigations into PRT-induced changes in clinical PC content and function.

Diagnosis and management of bone and joint infections (BJI) is a challenging task. The high intra and inter patient’s variability in terms of clinical presentation makes it impossible to rely on a systematic description or classical statistical analysis for its diagnosis. Advances can be achieved through a better understanding of the system behavior that results from the interactions between the components at a micro-scale level, which is difficult to mastered using traditional methods. Multiple studies from the literature report factors and interactions that affect the dynamics of the BJI system. The objectives of this study were (i) to perform a systematic review to identify relevant interactions between agents (cells, pathogens) and parameters values that characterize agents and interactions, and (ii) to develop a two dimensional computational model of the BJI system based on the results of the systematic review. The model would simulate the behavior resulting from the interactions on the cellular and molecular levels to explore the BJI dynamics, using an agent-based modeling approach. The BJI system’s response to different microbial inoculum levels was simulated. The model succeeded in mimicking the dynamics of bacteria, the innate immune cells, and the bone mass during the first stage of infection and for different inoculum levels in a consistent manner. The simulation displayed the destruction in bone tissue as a result of the alteration in bone remodeling process during the infection. The model was used to generate different patterns of system behaviors that could be analyzed in further steps. Simulations results suggested evidence for the existence of latent infections. Finally, we presented a way to analyze and synthesize massive simulated data in a concise and comprehensive manner based on the semi-supervised identification of ordinary differential equations (ODE) systems. It allows to use the known framework for temporal and structural ODE analyses and therefore summarize the whole simulated system dynamical behavior. This first model is intended to be validated by in vivo or in vitro data and expected to generate hypotheses to be challenged by real data. Step by step, it can be modified and complexified based on the test/validation iteration cycles.

BackgroundThe COVID-19 pandemic has negatively affected physical and mental health worldwide. Pregnant women already exhibit an elevated risk for depression compared to the general public, a pattern expected to be exacerbated by the pandemic. Certain lifestyle factors, including moderate exercise, may help support mental health during pregnancy, but it is unclear how the pandemic may impact these associations across different locations. Here, we test whether: (i) reported exercise routine alterations during the pandemic are associated with depression scores; and, (ii) the likelihood of reporting pandemic-related exercise changes varies between women living in metro areas and those in non-metro areas.MethodsThis cross-sectional study used data from the COVID-19 And Reproductive Effects (CARE) study, an online survey of pregnant women in the United States. Participants were recruited April-June 2020 (n = 1,856). Linear regression analyses assessed whether reported COVID-19-related exercise change was associated with depression score as measured by the Edinburgh Postnatal Depression Survey. Logistic regression analyses tested whether a participant's Rural-Urban Continuum Code classification of "metro" was linked with higher odds of reporting exercise changes compared to a "non-metro" classification.ResultsWomen who reported exercise changes during the pandemic exhibited significantly higher depression scores compared to those reporting no changes. Moreover, individuals living in metro areas of all sizes were significantly more likely to report exercise changes compared to women living in non-metro areas.ConclusionsThese results suggest that the ability to maintain an exercise routine during the pandemic may help support maternal mental health. It may therefore be prudent for providers to explicitly ask patients how the pandemic has impacted their exercise routines and consider altered exercise routines a potential risk factor for depression. An effort should also be made to recommend exercises that are tailored to individual space restrictions and physical health.

Bartonellae are bacteria associated with mammals and their ectoparasites. Rodents often host different species of Bartonella. The aim of this study was to investigate the presence of Bartonella spp. in African giant pouched rats (Cricetomys gambianus) and their ectoparasites in Dakar, Senegal. In 2012, 20 rats were caught, and their fleas were identified. DNA was extracted from 170 selected fleas and qPCR was carried out to detect Bartonella spp. Subsequently, a Bartonella culture was performed from the rat blood samples and the isolated strains (16S rRNA, rpoB, ftsZ and ITS3) were genotyped. A total of 1117 fleas were collected from 19 rats and identified as Xenopsylla cheopis, the tropical rat flea. Bartonella DNA was detected in 148 of 170 selected fleas (87.1%). In addition, Bartonella strains were isolated from the blood of 17 rats (85%). According to Bartonella gene-sequence-based criteria for species definition, the isolated strains were identified as B. massiliensis (four strains) and two potential new species related to the zoonotic B. elizabethae. In this paper, these potentially new species are provisionally called Candidatus Bartonella militaris (11 strains) and Candidatus Bartonella affinis (two strains) until their description has been completed. Cricetomys gambianus and its fleas could constitute a public health risk in Dakar due to the high prevalence of Bartonella infection reported.