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Immunogenicity is the propensity of a therapeutic protein to generate an immune response to itself. While reporting of antidrug antibodies (ADAs) is increasing, model‐based analysis of such data is seldom performed. Model‐based characterization of factors affecting the emergence and dissipation of ADAs may inform drug development and/or improve understanding in clinical practice. This analysis aimed to predict ADA dynamics, including the potential influence of individual covariates, following subcutaneous satralizumab administration. Satralizumab is a humanized IgG2 monoclonal recycling IL‐6 receptor antagonist antibody approved for treating neuromyelitis optica spectrum disorder (NMOSD). Longitudinal pharmacokinetic (PK) and ADA data from 154 NMOSD patients in two pivotal Phase 3 studies (NCT02028884, NCT02073279) and PK data from one Phase 1 study (SA‐001JP) in 72 healthy volunteers were available for this analysis. An existing population PK model was adapted to derive steady‐state concentration without ADA for each patient. A mixed hidden Markov model (mHMM) was developed whereby three different states were identified: one absorbing Markov state for non‐ADA developer, and two dynamic and inter‐connected Markov states—transient ADA negative and positive. Satralizumab exposure and body mass index impacted transition probabilities and, therefore, the likelihood of developing ADAs. In conclusion, the mHMM model was able to describe the time course of ADA development and identify patterns of ADA development in NMOSD patients following treatment with satralizumab, which may allow for the formulation of strategies to reduce the emergence or limit the impact of ADA in the clinical setting. [ABSTRACT FROM AUTHOR]

The application of iron oxide quantum dots (IOQDs) in this study led to the development of a straightforward, easy, and selective approach for cytosine sensing. To examine the capability of IOQDs in detecting nucleobases, attempts have been made to gain insight into the characteristics of IOQDs, including UV/Vis spectroscopic analysis, infrared spectroscopy, fluorescence spectroscopy, transmission electron microscopy, and powder‐XRD. We introduced IOQDs with a mean particle size distribution of 5.71 ± 0.08 nm for detecting cytosine by harnessing a turn‐on fluorescence phenomenon. The fostering fluorescence response of IOQDs was triggered in the presence of cytosine. In comparison, the presence of other nucleobases did not further induce the fluorescence signal of IOQDs. It was concluded that the hydrogen bonding bridging the carboxylate and hydroxyl groups on the surface of QDs with the amine groups of cytosine results in the elevation of IOQDs fluorescence. [ABSTRACT FROM AUTHOR]

Spatial scan statistics are well‐known methods widely used to detect spatial clusters of events. Furthermore, several spatial scan statistics models have been applied to the spatial analysis of time‐to‐event data. However, these models do not take account of potential correlations between the observations of individuals within the same spatial unit or potential spatial dependence between spatial units. To overcome this problem, we have developed a scan statistic based on a Cox model with shared frailty and that takes account of the spatial dependence between spatial units. In simulation studies, we found that (i) conventional models of spatial scan statistics for time‐to‐event data fail to maintain the type I error in the presence of a correlation between the observations of individuals within the same spatial unit and (ii) our model performed well in the presence of such correlation and spatial dependence. We have applied our method to epidemiological data and the detection of spatial clusters of mortality in patients with end‐stage renal disease in northern France. [ABSTRACT FROM AUTHOR]

Issues of reliability are claiming center‐stage in the epistemology of machine learning. This paper unifies different branches in the literature and points to promising research directions, whilst also providing an accessible introduction to key concepts in statistics and machine learning – as far as they are concerned with reliability. [ABSTRACT FROM AUTHOR]

Many types of cardiovascular disease are linked to the mechanical forces placed on the heart. However, our understanding of how mechanical forces exactly affect the cellular biology of the heart remains incomplete. In vitro models based on cardiomyocytes derived from human induced pluripotent stem cells (iPSC‐CM) enable researchers to develop medium to high‐throughput systems to study cardiac mechanobiology at the cellular level. Previous models have been developed to enable the study of mechanical forces, such as cardiac afterload. However, most of these models require exogenous extracellular matrix (ECM) to form cardiac tissues. Recently, a system was developed to simulate changes in afterload by grafting ECM‐free micro‐heart muscle arrays to elastomeric substrates of discrete stiffnesses. In the present study, we extended this system by combining the elastomer‐grafted tissue arrays with a magnetorheological elastomeric substrate. This system allows iPSC‐CM based micro‐heart muscle arrays to experience dynamic changes in contractile resistance to mimic dynamically altered afterload. Acute changes in substrate stiffness led to acute changes in the calcium dynamics and contractile forces, illustrating the system's ability to dynamically elicit changes in tissue mechanics by dynamically changing contractile resistance. [ABSTRACT FROM AUTHOR]

We studied grafted tumors obtained by subcutaneous implantation of kidney cancer cells into male white rats. Gold nanorods with a plasmon resonance of about 800 nm were injected intratumorally for photothermal heating. Experimental irradiation of tumors was carried out percutaneously using a near‐infrared diode laser. Changes in the optical properties of the studied tissues in the spectral range 350–2200 nm under plasmonic photothermal therapy (PPT) were studied. Analysis of the observed changes in the absorption bands of water and hemoglobin made it possible to estimate the depth of thermal damage to the tumor. A significant decrease in absorption peaks was observed in the spectrum of the upper peripheral part and especially the tumor capsule. The obtained changes in the optical properties of tissues under laser irradiation can be used to optimize laboratory and clinical PPT procedures. [ABSTRACT FROM AUTHOR]

Laser generation of NV‐centers in diamond with pulse energy up to 48 μJ and efficiency about 1% is performed. Also, we observe strong influence of low‐intensity short‐wavelength irradiation on pulse energy: in presence of this irradiation the pulse energy increased by factor up to 3.5. Additionally, we make an attempt to estimate theoretically our samples' gain coefficient. GA. Laser generation with pulse energy up to 48 μJ and efficiency about 1% is performed using diamond, containing NV‐centers, as laser active element. Diamond crystal was pumped by 532 by 532 nm radiation. Also, strong influence of low‐intensity short‐wavelength irradiation on pulse energy is observed: in presence of this irradiation the pulse energy increased by factor up to 3.5. [ABSTRACT FROM AUTHOR]

Dynamically evolving adhesions between cells and extracellular matrix (ECM) transmit time‐varying signals that control cytoskeletal dynamics and cell fate. Dynamic cell adhesion and ECM stiffness regulate cellular mechanosensing cooperatively, but it has not previously been possible to characterize their individual effects because of challenges with controlling these factors independently. Therefore, a DNA‐driven molecular system is developed wherein the integrin‐binding ligand RGD can be reversibly presented and removed to achieve cyclic cell attachment/detachment on substrates of defined stiffness. Using this culture system, it is discovered that cyclic adhesion accelerates F‐actin kinetics and nuclear mechanosensing in human mesenchymal stem cells (hMSCs), with the result that hysteresis can completely change how hMSCs transduce ECM stiffness. Results are dramatically different from well‐known results for mechanotransduction on static substrates, but are consistent with a mathematical model of F‐actin fragments retaining structure following loss of integrin ligation and participating in subsequent repolymerization. These findings suggest that cyclic integrin‐mediated adhesion alters the mechanosensing of ECM stiffness by hMSCs through transient, hysteretic memory that is stored in F‐actin. [ABSTRACT FROM AUTHOR]

Back‐to‐back marine heatwaves in 2016 and 2017 resulted in severe coral bleaching and mortality across the Great Barrier Reef (GBR). Encouragingly, some corals that survived these events exhibit increased bleaching resistance and may represent thermally tolerant populations that can better cope with ocean warming. Using the GBR as a natural laboratory, we investigated whether a history of minimal (Heron Island) or severe (Lizard Island) coral bleaching in 2016 and 2017 equates to stress tolerance in a successive heatwave (2020). We examined the genetic diversity, physiological performance, and trophic plasticity of juvenile (<10 cm) and adult (>25 cm) corals of two common genera (Pocillopora and Stylophora). Despite enduring greater cumulative heat stress (6.3°C week−1 vs. 5.6°C week−1), corals that experienced the third marine heatwave in 5 years (Lizard) exhibited twice as high survival and visual bleaching thresholds compared to corals that had not experienced significant bleaching in >10 years (Heron). Surprisingly, only one shared host–Symbiodiniaceae association was uncovered between locations (Stylophora pistillata–Cladocopium "C8 group") and there was no genetic overlap in Pocillopora–Cladocopium partnerships, suggesting turnover in species composition from recent marine heatwaves. Corals within the species complex Pocillopora that survived the 2016 and 2017 marine heatwaves at Lizard Island were the most resilient, exhibiting three times greater calcification rates than conspecifics at Heron Island. Further, surviving corals (Lizard) had distinct isotopic niches, lower host carbon, and greater host protein, while conspecifics that had not experienced recent bleaching (Heron) had two times greater symbiont carbon content, suggesting divergent trophic strategies that influenced survival (i.e., greater reliance on heterotrophy vs. symbiont autotrophy, respectively). Ultimately, while corals may experience less bleaching and survive repeated thermal stress events, species‐specific trade‐offs do occur, leaving open many questions related to the long‐term health and recovery of coral reef ecosystems in the face of intensifying marine heatwaves. [ABSTRACT FROM AUTHOR]

Background: The rapid detection and efficient properties of surface‐enhanced Raman scattering (SERS) have been widely exploited in food safety. Purpose: In this study, the SERS impact of cysteine‐functionalized gold core‐silver shell bimetallic nanoparticle (Au@Ag@CysNPs) substrates with different pH treatments on pesticide compounds was examined. Results: The pH‐dependent SERS impact of Au@Ag@CysNPs on detecting pesticide compounds exhibited different enhancements over the pH range of 2–11 and exited the highest enhancement at a pH of 5 for thiabendazole and thiram pesticides. The prepared Au@Ag@CysNPs were further utilized in SERS‐based rapid detection of pesticides on apple peels by directly dropping Au@Ag@CysNPs on the surface of the samples, where the target molecules could be identified without elution or extraction. These findings revealed that this Au@Ag@CysNPs substrate exhibited excellent SERS performances for pesticide compounds and good stability. With additional optimization, detection limits of 0.1 ng/cm2 for thiabendazole and thiram on apple peels were obtained. [ABSTRACT FROM AUTHOR]

Information processing using material's own properties has gained increasing interest. Mechanical metamaterials, due to their diversity of deformation modes and wide design space, can be used to realize information processing, such as computing and storage. Here a mechanical metamaterial system is demonstrated for material‐based encoding and storage of data through programmed reconfigurations of the metamaterial's structured building blocks. Sequential encoding and decoding are achieved in the three‐dimensional (3D) printed pixelated mechanical metamaterial via kirigami‐based "pixels" with programmable, temperature‐dependent bistability. The mechanical metamaterial is demonstrated via a multistep deformation of encoding messages of texts and surfaces with arrays of binary data, and then decoding them by applying a predetermined stretching and heating regimen to sequentially retrieve layers of stored information and display them on its surface. This approach serves as a general framework to enable the encoding and storage of data with mechanical metamaterials. [ABSTRACT FROM AUTHOR]

In this paper, we report a sensitive surface‐enhanced Raman scattering (SERS) biosensor for the detection of food‐borne pathogens on the basis of recognition of bacterial cells through the specific targeting agent vancomycin. Vancomycin‐functionalized gold nanostars (GNSs–4–MBA–van) were synthesized as SERS tags for specific and sensitive quantification of food pathogens. The Raman reporter molecule 4–mercaptobenzoic acid (4–MBA) was also a linker molecule to attach vancomycin to gold nanostars. The proposed vancomycin‐based SERS technique achieved a detection limit of 5.7 and 8.2 CFU/ml for Staphylococcus aureus and Escherichia coli, respectively. The logarithm of the bacterial concentration ranged from 101 to 107 CFU/ml and demonstrated a linear relationship with the SERS intensity of the characteristic 4–MBA Raman peak at 1,081 cm−1. Principle component analysis was used to discriminate the two pathogens simultaneously by using reproducible and specific intrinsic fingerprints and intracellular components obtained through SERS. Moreover, the spiking tests revealed that GNSs–4–MBA–van is effective as a potential biosensor for detecting pathogens in the fresh meat and food‐processing industries. [ABSTRACT FROM AUTHOR]

Arrhythmogenic cardiomyopathy with right dominant form (ACR) is a rare heritable cardiac cardiomyopathy disorder associated with sudden cardiac death. Pathogenic variants (PVs) in desmosomal genes have been causally related to ACR in 40% of cases. Other genes encoding nondesmosomal proteins have been described in ACR, but their contribution in this pathology is still debated. A panel of 71 genes associated with inherited cardiopathies was screened in an ACR population of 172 probands and 856 individuals from the general population. PVs and uncertain significance variants (VUS) have been identified in 36% and 18.6% of patients, respectively. Among the cardiopathy‐associated genes, burden tests show a significant enrichment in PV and VUS only for desmosomal genes PKP2 (plakophilin‐2), DSP (desmoplakin), DSC2 (desmocollin‐2), and DSG2 (desmoglein‐2). Importantly, VUS may account for 15% of ACR cases and should then be considered for molecular diagnosis. Among the other genes, no evidence of enrichment was detected, suggesting an extreme caution in the interpretation of these genetic variations without associated functional or segregation data. Genotype–phenotype correlation points to (1) a more severe and earlier onset of the disease in PV and VUS carriers, underlying the importance to carry out presymptomatic diagnosis in relatives and (2) to a more prevalent left ventricular dysfunction in DSP variant carriers. [ABSTRACT FROM AUTHOR]

Here we calculate T1→S0 transition energies in nine phosphorescent iridium complexes using the iterative qubit coupled cluster (iQCC) method to determine if quantum simulations have any advantages over classical methods. These simulations would require a gate‐based quantum computer with at least 72 fully‐connected logical qubits. Since such devices do not yet exist, we demonstrate the iQCC method using a purpose‐built quantum simulator on classical hardware. The results are compared to a selection of common DFT functionals, ab initio methods, and empirical data. iQCC is found to match the accuracy of the best DFT functionals, but with a better correlation coefficient, demonstrating that it is better at predicting the structure–property relationship. Results indicate that the iQCC method has the required accuracy to design organometallic complexes when deployed on emerging quantum hardware and sets an industrially relevant target for demonstrating quantum advantage. [ABSTRACT FROM AUTHOR]

Ralstonia solanacearum gram‐negative phytopathogenic bacterium exerts its virulence through a type III secretion system (T3SS) that translocates type III effectors (T3Es) directly into the host cells. T3E secretion is finely controlled at the posttranslational level by helper proteins, T3SS control proteins, and type III chaperones. The HpaP protein, one of the type III secretion substrate specificity switch (T3S4) proteins, was previously highlighted as a virulence factor on Arabidopsis thaliana Col‐0 accession. In this study, we set up a genome‐wide association analysis to explore the natural diversity of response to the hpaP mutant of two A. thaliana mapping populations: a worldwide collection and a local population. Quantitative genetic variation revealed different genetic architectures in both mapping populations, with a global delayed response to the hpaP mutant compared to the GMI1000 wild‐type strain. We have identified several quantitative trait loci (QTLs) associated with the hpaP mutant inoculation. The genes underlying these QTLs are involved in different and specific biological processes, some of which were demonstrated important for R. solanacearum virulence. We focused our study on four candidate genes, RKL1, IRE3, RACK1B, and PEX3, identified using the worldwide collection, and validated three of them as susceptibility factors. Our findings demonstrate that the study of the natural diversity of plant response to a R. solanacearum mutant in a key regulator of virulence is an original and powerful strategy to identify genes directly or indirectly targeted by the pathogen. [ABSTRACT FROM AUTHOR]

The plant pathogen Ralstonia solanacearum uses plant resources to intensely proliferate in xylem vessels and provoke plant wilting. We combined automatic phenotyping and tissue/xylem quantitative metabolomics of infected tomato plants to decipher the dynamics of bacterial wilt. Daily acquisition of physiological parameters such as transpiration and growth were performed. Measurements allowed us to identify a tipping point in bacterial wilt dynamics. At this tipping point, the reached bacterial density brutally disrupts plant physiology and rapidly induces its death. We compared the metabolic and physiological signatures of the infection with drought stress, and found that similar changes occur. Quantitative dynamics of xylem content enabled us to identify glutamine (and asparagine) as primary resources R. solanacearum consumed during its colonization phase. An abundant production of putrescine was also observed during the infection process and was strongly correlated with in planta bacterial growth. Dynamic profiling of xylem metabolites confirmed that glutamine is the favoured substrate of R. solanacearum. On the other hand, a triple mutant strain unable to metabolize glucose, sucrose and fructose appears to be only weakly reduced for in planta growth and pathogenicity. [ABSTRACT FROM AUTHOR]

Tracking the movement of all individual group members in their natural environment remains a challenging task. Using advances in computer vision and Deep Learning, we developed and tested a semi‐automated in situ tracking system to reconstruct simultaneous three‐dimensional trajectories of marked individuals in social groups of a coral‐reef fish. Our system has a temporal resolution of 10s of milliseconds, allowing for multiple 30‐min tracking sessions that have been repeated over weeks to months. We present the technique and illustrate its application for Dascyllus marginatus, a planktivorous damselfish that lives in social groups associated with branching corals. Our technique identified all individuals 85–100% of the time, with a mean spatial error of ~ 1.3 cm. It provides a cost‐effective semi‐automated tool for in situ research on movements and foraging of individuals within small site‐attached groups of animals in their natural environment. [ABSTRACT FROM AUTHOR]

Background: The institutionalization of a patient with Alzheimer's disease or other dementia (ADOD) is the last resort for the latter's family and/or caregivers. We hypothesized that the degree of kinship between the patient and his/her caregiver would influence the likelihood of institutionalization. Objective: To assess the association between institutionalization of patients with ADOD and the degree of kinship with the family caregiver. Methods: A cross‐sectional study of patients with ADOD aged 75 or over attending a memory center in France for the first time between 2011 and 2014, as recorded in the French National Alzheimer Database. Multivariable logistic regression was used to assess factors associated with institutionalization after adjustment for age, sex, the Mini‐Mental State Examination score, educational level, and type of dementia. Results: A total of 52,874 patients were included. The primary caregiver was most often a child (54.8%) or the spouse (36.7%). Compared with the "spouse" reference category, all the other caregiver categories were associated with a significantly greater likelihood of institutionalization; the odds ratio [95% confidence interval] was 4.68 [3.67–5.92] when the carer was a grandchild, 5.48 [4.93–6.09] for a child, 4.93 [4.11–5.91] for a daughter‐/son‐in‐law, 8.76 [7.15–10.70] for a sibling, and 8.93 [7.48–10.65] for a niece/nephew. Conclusion: The likelihood of institutionalization of older patients with ADOD varied with the degree of kinship. Compared with the "spouse" reference category, the likelihood was higher for all other types of caregivers but was especially high when the caregiver was not a direct descendant of the patient. [ABSTRACT FROM AUTHOR]

Hydrogels are commonly doped with stiff nanoscale fillers to endow them with the strength and stiffness needed for engineering applications. Although structure–property relations for many polymer matrix nanocomposites are well established, modeling the new generation of hydrogel nanocomposites requires the study of processing–structure–property relationships because subtle differences in chemical kinetics during their synthesis can cause nearly identical hydrogels to have dramatically different mechanical properties. The authors therefore assembled a framework to relate synthesis conditions (including hydrogel and nanofiller mechanical properties and light absorbance) to gelation kinetics and mechanical properties. They validated the model against experiments on a graphene oxide (GO) doped oligo (ethylene glycol) diacrylate (OEGDA), a system in which, in apparent violation of laws from continuum mechanics, doping can reduce rather than increase the stiffness of the resulting hydrogel nanocomposites. Both model and experiment showed a key role light absorbance‐dominated gelation kinetics in determining nanocomposite mechanical properties in conjunction with nanofiller reinforcement, with the nanofiller's attenuation of chemical kinetics sometimes outweighing stiffening effects to explain the observed, anomalous loss of stiffness. By bridging the chemical kinetics and mechanics of nanocomposite hydrogels, the authors' modeling framework shows promise for broad applicability to design of hydrogel nanocomposites. [ABSTRACT FROM AUTHOR]

Many cell responses that underlie the development, maturation, and function of tissues are guided by the architecture and mechanical loading of the extracellular matrix (ECM). Because mechanical stimulation must be transmitted through the ECM architecture, the synergy between these two factors is important. However, recapitulating the synergy of these physical microenvironmental cues in vitro remains challenging. To address this, a 3D magnetically actuated collagen hydrogel platform is developed that enables combined control of ECM architecture and mechanical stimulation. With this platform, it is demonstrated how these factors synergistically promote cell alignment of C2C12 myoblasts and enhance myogenesis. This promotion is driven in part by the dynamics of Yes‐associated protein and structure of cellular microtubule networks. This facile platform holds great promises for regulating cell behavior and fate, generating a broad range of engineered physiologically representative microtissues in vitro, and quantifying the mechanobiology underlying their functions. [ABSTRACT FROM AUTHOR]

Despite suggestions that turbulence can affect the migration of zooplankton, field observations of such effects are scarce. This is especially the case for bottom-associated (demersal) zooplankton that reside in the typically turbulent near-bottom environment. Using moored sensors deployed at two coastal sites in the North Pacific and the Red Sea, we present observations of the effects of turbulence on the nocturnal emergence of demersal zooplankton. A cabled observatory consisting of a plankton camera, an acoustic current profiler and environmental sensors, was deployed near bottom in 20 m of water near Oshima Island, Japan. Observations were also obtained from a second site near a coral reef in 16 m of water in the Red Sea. Acoustic backscatter data obtained from current profilers at both sites provided a proxy for zooplankton density. Combined with simultaneous estimates of turbulence intensity, the observations suggest that the nocturnal emergence of demersal zooplankton was hindered by elevated levels of turbulence. While our findings are inferred from acoustic data, agreement between the two different sites supports our hypothesis that demersal zooplankton may remain near the bed during times of strong turbulence. [ABSTRACT FROM AUTHOR]

Photoresponsive hydrogels (PRHs) are soft materials whose mechanical and chemical properties can be tuned spatially and temporally with relative ease. Both photo‐crosslinkable and photodegradable hydrogels find utility in a range of biomedical applications that require tissue‐like properties or programmable responses. Progress in engineering with PRHs is facilitated by the development of theoretical tools that enable optimization of their photochemistry, polymer matrices, nanofillers, and architecture. This review brings together models and design principles that enable key applications of PRHs in tissue engineering, drug delivery, and soft robotics, and highlights ongoing challenges in both modeling and application. [ABSTRACT FROM AUTHOR]

This paper introduces a new spatial scan statistic designed to adjust cluster detection for longitudinal confounding factors indexed in space. The functional-model-adjusted statistic was developed using generalized functional linear models in which longitudinal confounding factors were considered to be functional covariates. A general framework was developed for application to various probability models. Application to a Poisson model showed that the new method is equivalent to a conventional spatial scan statistic that adjusts the underlying population for covariates. In a simulation study with single and multiple covariate models, we found that our new method adjusts the cluster detection procedure more accurately than other methods. Use of the new spatial scan statistic was illustrated by analyzing data on premature mortality in France over the period from 1998 to 2013, with the quarterly unemployment rate as a longitudinal confounding factor. [ABSTRACT FROM AUTHOR]

Summary: The prognostic value of cell of origin (COO) classification and BCL2 expression is not well established in diffuse large B‐cell lymphoma (DLBCL) patients with human immunodeficiency virus (HIV) infection in the recent era. Phenotypic patterns were determined by immunohistochemistry (IHC) of pathological samples from patients with HIV‐associated DLBCL prospectively enrolled in the French AIDS and Viral Hepatitis CO16 Lymphovir cohort between 2008 and 2015. Molecular subgroup classification into germinal centre B‐cell (GCB) and non‐GCB subtypes was determined using the Hans algorithm. Among 52 samples of systemic DLBCL subjected to centralized pathological analysis, 25 of the 42 tested for BCL2 expression were positive. Samples were further classified into GCB (n = 19) and non‐GCB (n = 16) subtypes and 17 remained unclassified. In multivariable analysis, BCL2 expression was an independent pejorative prognostic biomarker [4‐year progression‐free survival (PFS): 52% for BCL2+ vs. 88% for BCL2−, P = 0·02] and tended to reduce 4‐year overall survival (OS) (63% for BCL2+ vs. 88% for BCL2−, P = 0·06). The difference between CGB and non‐GCB subtypes on PFS and OS did not reach significance (4‐year PFS: 79% for GCB vs. 53% for non‐GCB, P = 0·24 and 4‐year OS: 78% for GCB vs. 69% for non‐GCB, P = 0·34). BCL2 expression determined by IHC is an independent pejorative prognostic biomarker in HIV‐associated DLBCL in the recent era. This supports the investigation of new therapeutic strategies in patients with BCL2 expression. [ABSTRACT FROM AUTHOR]

Summary: Background: Geographical variations in Crohn's disease (CD) suggest that the environment has a role in the pathogenesis of this condition. Aims: To describe the spatial distribution and the clustering of CD cases in France, and to assess the relationship between the prevalence of CD and environmental risk factors. Methods: We identified all patients with CD included in the French hospital discharge database from 2007 to 2014. Age‐ and gender‐smoothed standardised prevalence ratios over this period were computed for 5610 spatial units. An ecological regression analysis was used to assess the relationship between the risk of CD and ecological variables (health care, latitude, socio‐economic deprivation, urbanisation, proportion of agricultural surfaces and density of industries). Local spatial clusters of high‐CD prevalence were searched for using elliptic spatial scan statistics and characterised in a hierarchical ascendant classification based on the same ecological variables. Results: About 129 089 patients with CD were identified, yielding a crude prevalence of 203 per 100 000 inhabitants. The overall spatial heterogeneity was statistically significant (P <.001). An elevated risk of CD was found to be significantly associated with high‐social deprivation (relative risk [95% confidence interval] = 1.05 [1.02‐1.08]) and high urbanisation (1.09 [1.04‐1.14]). Sixteen significant spatial clusters of high‐CD prevalence were identified; there were no common ecological variables. Conclusions: The geographical distribution of CD prevalence in France is not uniform, and is associated with high levels of social deprivation and urbanisation. Larger ecological databases integrating more detailed environmental and clinical information are needed. [ABSTRACT FROM AUTHOR]

Salps are gelatinous planktonic suspension feeders that filter large volumes of water in the food‐dilute open ocean. Their life cycle allows periodic exponential growth and population blooms. Dense swarms of salps have a high grazing impact that can deplete the photic zone of phytoplankton and export huge quantities of organic matter to the deep sea. Previous studies described their feeding manner as mostly nonselective, with larger particles retained at higher efficiencies than small particles. To examine salp diets, we used direct in situ sampling (InEx method) of undisturbed solitary Salpa maxima. Aggregates ("chains") of Salpa fusiformis and Thalia democratica were studied using in situ incubations. Our findings suggest that in situ feeding rates are higher than previously reported and that cell removal is size independent with ∼ 1 μm picoeukaryotes preferentially removed over both larger eukaryotes and smaller bacteria. The prey : predator size ratios we measured (1 : 104–1 : 105) are an order of magnitude smaller than previously reported values and to the best of our knowledge, are the smallest values reported so far for any planktonic suspension feeders. Despite differences among the three species studied, they had similar prey preferences with no correlation between salp body length and prey size. Our findings shed new light on prey : predator relationships in planktonic systems—in particular, that factors other than size influence filtration efficiency—and suggest that in situ techniques should be devised and applied for the study of suspension feeding in the ocean. [ABSTRACT FROM AUTHOR]

Submersible fluorescence and turbidity sensors are widely used in studies of oceans and lakes. To reduce the instrument size, an overlapping interrogation volume is commonly used for the two sensors. Fluorescence sensors emit blue light for excitation and measure the red light emitted by excited chlorophyll pigments. However, during the night, many phototactic zooplankters are attracted to the blue light. If the instrument is fixed in place (e.g., on a mooring), the aggregation of the attracted animals may bias both the fluorescence and turbidity readings. To examine this potential bias, we carried out experiments with natural assemblages of zooplankton and Artemia nauplii in tanks equipped with a commercially available fluorescence‐turbidity sensor. Our findings indicate that zooplankters were attracted by the blue light emitted from a fluorometer during the dark, biasing the reading of both sensors. The bias in fluorescence was likely due to phytoplankton in the guts of the aggregated zooplankton. The induction of turbulence in the tank greatly reduced the bias, likely due to the inability of the zooplankton to counteract the resulting flow and swim toward the light. Field observations carried out with a similar instrument in a coastal station off Japan were consistent with the laboratory experiments. Our findings indicate a need to redesign coupled fluorescence‐turbidity sensors and to reevaluate the results of past studies where they had been used with stationary observing systems. [ABSTRACT FROM AUTHOR]

Summary: An evolution experiment with the bacterial plant pathogen Ralstonia solanacearum revealed that several adaptive mutations conferring enhanced fitness in plants arose in the efpR gene encoding a regulator of virulence and metabolic functions. In this study, we found that an efpR mutant systematically displays colonies with two morphotypes: the type S ('smooth', similar to the wild type) and the type EV ('efpR variant'). We demonstrated that the efpH gene, a homologue of efpR, plays a key role in the control of phenotypic heterogeneity, the ΔefpR‐ΔefpH double mutant being stably locked into the EV type. Using mixed infection assays, we demonstrated that the type EV is metabolically more proficient than the type S and displays fitness gain in specific environments, whereas the type S has a better fitness into the plant environment. We provide evidence that this efpR‐dependent phenotypic heterogeneity is a general feature of strains of the R. solanacearum species complex and could occur in natural conditions. This study highlights the potential role of phenotypic heterogeneity in this plant pathogen as an adaptive trait to changing environments. [ABSTRACT FROM AUTHOR]

Purpose: Biomechanical properties can be used as biomarkers to diagnose tumors, monitor tumor development, and evaluate treatment efficacy. The purpose of this preliminary study is to characterize the biomechanical environment of two typical liver tumors, hemangiomas (HEMs) and hepatocellular carcinomas (HCCs), and to investigate the potential of using strain metrics as biomarkers for tumor diagnosis, based on a limited clinical dataset. Methods: Magnetic resonance (MR) tagging was used to quantify the motion and deformation of the two types of liver tumors. Displacements of the tumors arising from a heartbeat were measured over one cardiac cycle. Local biomechanical conditions of the tumors were characterized by estimating two principal strains (ε1 and ε2) and an octahedral shear strain (εsoct) of the tumor and its peripheral region. Biomechanical conditions of the tumors were compared with those of the arbitrarily selected regions from healthy volunteers. Results: We observed that the HCCs had significantly smaller strain values compared to their peripheral tissues. However, the HEMs did not have significantly different strains from those of the peripheral tissues, and were similar to healthy liver regions. The sensitivity of using ε1, ε2, and εsoct to diagnose HCC were all 1, while the sensitivity of using ε1, ε2, and εsoct to diagnose HEM were 0.67, 0.17, and 0.67, respectively. Conclusions: Lagrangian strain metrics provide insight into the biomechanical conditions of certain liver tumors in the human body and may provide another perspective for tumor characterization and diagnosis. [ABSTRACT FROM AUTHOR]

Reunion Island is a French oversea department in the Indian Ocean with 1.6/1000, an estimated prevalence of deafness that is almost double as compared to the mainland France. Twelve children having isolated bilateral prelingual profound deafness along with motor delay attributed to vestibular areflexia were enrolled. Their mean walking age was 19 months. Electroretinography and temporal bone CT‐scans were normal in all cases. A novel homozygous frameshift lipoma HMGIC fusion partner‐like 5 (LHFPL5) variant c.185delT p.(Phe62Serfs*23) was identified using whole‐exome sequencing. It was found in seven families. Four patients from two different families from both Reunion Island and mainland France, were compound heterozygous: c.185delT p.(Phe62Serfs*23) and c.472C > T p.(Arg158Trp). The phenotype observed in our patients completely mimics the hurry‐scurry (hscy) murine Tmhs knock‐out model. The recurrent occurrence of same LHFPL5 variant in Reunion Island is attributed to common ancestor couple born in 1693. A highest prevalence of congenital deafness is noticed among the Reunionese population with a similar phenotype: isolated bilateral profound congenital deafness with motor delay because of bilateral vestibular areflexia without cochleo‐vestibular malformation and Retinitis Pigmentosa. A novel homozygous frameshift lipoma HMGIC fusion partner‐like 5 (LHFPL5) variant c.185delT p.(Phe62Serfs*23) was identified using WES. A founder effect was determined thanks to the founder haplotype and the common ancestor couple, born in 1693. [ABSTRACT FROM AUTHOR]

Summary: To deploy durable plant resistance, we must understand its underlying molecular mechanisms. Type III effectors (T3Es) and their recognition play a central role in the interaction between bacterial pathogens and crops. We demonstrate that the Ralstonia solanacearum species complex (RSSC) T3E ripAX2 triggers specific resistance in eggplant AG91‐25, which carries the major resistance locus EBWR9. The eggplant accession AG91‐25 is resistant to the wild‐type R. pseudosolanacearum strain GMI1000, whereas a ripAX2 defective mutant of this strain can cause wilt. Notably, the addition of ripAX2 from GMI1000 to PSS4 suppresses wilt development, demonstrating that RipAX2 is an elicitor of AG91‐25 resistance. RipAX2 has been shown previously to induce effector‐triggered immunity (ETI) in the wild relative eggplant Solanum torvum, and its putative zinc (Zn)‐binding motif (HELIH) is critical for ETI. We show that, in our model, the HELIH motif is not necessary for ETI on AG91‐25 eggplant. The ripAX2 gene was present in 68.1% of 91 screened RSSC strains, but in only 31.1% of a 74‐genome collection comprising R. solanacearum and R. syzygii strains. Overall, it is preferentially associated with R. pseudosolanacearum phylotype I. RipAX2GMI1000 appears to be the dominant allele, prevalent in both R. pseudosolanacearum and R. solanacearum, suggesting that the deployment of AG91‐25 resistance could control efficiently bacterial wilt in the Asian, African and American tropics. This study advances the understanding of the interaction between RipAX2 and the resistance genes at the EBWR9 locus, and paves the way for both functional genetics and evolutionary analyses. [ABSTRACT FROM AUTHOR]

Novel wetting strategies in plants have inspired numerous notable biomimetic surfaces over the past decade, such as self-cleaning surfaces mimicking the water repellency of lotus leaves and directional water transport surfaces imitating the slippery surface on carnivorous plants. Here, a new wetting behavior in dandelion seed (genus Taraxacum) is found, characterized by capturing a droplet inside it. The critical conditions required for wetting of the fiber assay in terms of the fibrous geometry and liquid surface tension are identified, and how these factors quantitatively affect the volume of the captured droplet is shown further. More importantly, the reverse process can be triggered by introducing a competitive liquid phase with smaller surface tension to the wetted fiber assay, as it is demonstrated by the release of the captured water droplet in oil. These results enhance the understanding on wetting of fibrous structures and would benefit the design of novel intelligent and responsive devices. This newly identified wetting behavior holds great potential for fine control and micromanipulation of liquid. As a demonstration, it is illustrated that the natural fibrous structure is capable of manipulating a small volume of liquid for droplet-based multiplexed chemical reaction. [ABSTRACT FROM AUTHOR]

Ralstonia solanacearum is a phytopathogenic bacterium that colonizes the xylem vessels of host plants leading to a lethal wilt disease. Although several studies have investigated the virulence of R. solanacearum on adult host plants, infection studies of this pathogen on the seedling stages of hosts are less common. In a preliminary observation, inoculation of R. solanacearum F1C1 on 6-to 7-day-old tomato seedlings by a simple leaf-clip strategy resulted in a lethal pathogenic condition in seedlings that eventually killed these seedlings within a week post-inoculation. This prompted testing of the effect of this inoculation technique in seedlings from different cultivars of tomato and similar results were obtained. Colonization and spread of the bacteria throughout the infected seedlings was demonstrated using gus-tagged R. solanacearum F1C1. The same method of inoculating tomato seedlings was used with R. solanacearum GMI1000 and independent mutants of R. solanacearum GMI1000, deficient in the virulence genes hrpB, hrpG, phcA and gspD. Wildtype R. solanacearum GMI1000 was found to be virulent on tomato seedlings, whereas the mutants were found to be non-virulent. This leaf-clip technique, for inoculation of tomato seedlings, has the potential to be a valuable approach, saving time, space, labour and costs. [ABSTRACT FROM AUTHOR]

In the past 2 decades, progress in molecular analyses of the plant immune system has revealed key elements of a complex response network. Current paradigms depict the interaction of pathogen-secreted molecules with host target molecules leading to the activation of multiple plant response pathways. Further research will be required to fully understand how these responses are integrated in space and time, and exploit this knowledge in agriculture. In this review, we highlight systems biology as a promising approach to reveal properties of molecular plant-pathogen interactions and predict the outcome of such interactions. We first illustrate a few key concepts in plant immunity with a network and systems biology perspective. Next, we present some basic principles of systems biology and show how they allow integrating multiomics data and predict cell phenotypes. We identify challenges for systems biology of plant-pathogen interactions, including the reconstruction of multiscale mechanistic models and the connection of host and pathogen models. Finally, we outline studies on resistance durability through the robustness of immune system networks, the identification of trade-offs between immunity and growth and in silico plant-pathogen co-evolution as exciting perspectives in the field. We conclude that the development of sophisticated models of plant diseases incorporating plant, pathogen and climate properties represent a major challenge for agriculture in the future. [ABSTRACT FROM AUTHOR]

Trichomes ('hair cells') on Arabidopsis thaliana stem and leaf surfaces provide a range of benefits arising from their shape and disposition. These include tempting herbivores to sample constitutive toxins before they reach the bulk of the tissue. We asked whether, in addition, small mechanical disturbances such as an insect can make elicit signals that might help the plant respond to herbivory. We imaged, pressed and brushed trichomes in several ways, most notably with confocal microscopy of trichomes transgenically provided with apoplastic pH reporter apo-pHusion and cytosolic Ca2+ reporter cameleon. In parallel, we modelled trichome wall mechanics with finite element analysis. The stimulated trichome focuses force on a pliant zone and the adjoining podium of the stalk. A buckling instability can further focus force on a skirt of cells surrounding the podium, eliciting oscillations of cytosolic Ca2+ and shifts in apoplastic pH. These observations represent active physiological response. Modelling establishes that the effectiveness of force focusing and buckling is due to the peculiar tapering wall structure of the trichome. Hypothetically, these active mechanosensing functions enhance toxin synthesis above constitutive levels, probably via a priming process, thus minimizing the costly accumulation of toxins in the absence of herbivore attack but assuring rapid build-up when needed. [ABSTRACT FROM AUTHOR]

Tandem uncaging systems in which a two-photon absorbing module and a cage moiety, linked via a phosphorous clip, that act together by Förster resonance energy transfer (FRET) have been developed. A library of these compounds, using different linkers and cages (7-nitroindolinyl or nitroveratryl) has been synthesized. The investigation of their uncaging and two-photon absorption properties demonstrates the scope and versatility of the engineering strategy towards efficient two-photon cages and reveals surprising cooperative and topological effects. The interactions between the 2PA module and the caging moiety are found to promote cooperative effects on the 2PA response while additional processes that enhance the uncaging efficiency are operative in well-oriented nitroindoline-derived dyads. These synergic effects combine to lead to record two-photon uncaging cross-section values (i.e., up to 20 GM) for uncaging of carboxylic acids. [ABSTRACT FROM AUTHOR]

The soil-borne pathogen R alstonia solanacearum causes bacterial wilt in a broad range of plants. The main virulence determinants of R . solanacearum are the type III secretion system ( T3SS) and its associated type III effectors ( T3Es), translocated into the host cells. Of the conserved T3Es among R . solanacearum strains, the Fbox protein RipG7 is required for R . solanacearum pathogenesis on M edicago truncatula. In this work, we describe the natural rip G 7 variability existing in the R . solanacearum species complex. We show that eight representative rip G 7 orthologues have different contributions to pathogenicity on M . truncatula: only rip G 7 from Asian or African strains can complement the absence of rip G 7 in GMI1000 ( Asian reference strain). Nonetheless, RipG7 proteins from American and Indonesian strains can still interact with M . truncatula SKP1-like/ MSKa protein, essential for the function of RipG7 in virulence. This indicates that the absence of complementation is most likely a result of the variability in the leucine-rich repeat ( LRR) domain of RipG7. We identified 11 sites under positive selection in the LRR domains of RipG7. By studying the functional impact of these 11 sites, we show the contribution of five positively selected sites for the function of RipG7CMR15 in M . truncatula colonization. This work reveals the genetic and functional variation of the essential core T3E RipG7 from R . solanacearum. This analysis is the first of its kind on an essential disease-controlling T3E, and sheds light on the co-evolutionary arms race between the bacterium and its hosts. [ABSTRACT FROM AUTHOR]

Summary: Background: While decreased physical activity and increased sedentary behaviours are incriminated for their role in the progression of obesity, active video games (AVG) may offer a new alternative to increase energy expenditure in youth. This study is the first to examine the effect of a 1‐h AVG play on lean and obese adolescents' energy expenditure. Methods: Body composition and aerobic fitness were assessed in 19 obese and 12 lean adolescent boys (12–15 years old). Participants performed a 1‐h AVG session (Kinect Sports technology) while wearing a portable indirect calorimeter (K4b2) to assess their energy expenditure and heart rate. Results: Body weight (91.0 ± 9.5 vs. 58.5 ± 12.4 kg), body mass index (32.2 ± 3.1 vs. 20.3 ± 1.6 kg m−2) and body fat (38.1 ± 2.7 vs. 13.4 ± 3.9%) were significantly higher in obese adolescents (P < 0.001). Absolute energy expenditure was significantly higher in obese (P < 0.05) but not when corrected for body composition. Maximal heart rate reached during AVG was significantly higher in lean adolescents (190 ± 25 vs. 183 ± 28 bpm, P < 0.05). Time spent between 3 and 6 METs (Metabolic Equivalent Task) was not different between groups but time spent above 6 METs was higher in lean adolescents (P < 0.05). Conclusion: Although lean and obese adolescent boys experienced similar energy expenditure relative to their body size during a 1‐h Kinect AVG session, lean adolescents spent more time in moderate‐to‐vigorous physical activity. [ABSTRACT FROM AUTHOR]

Coral branches partially block the flow of water through the colony, creating an inner zone of reduced water exchange where hypoxic conditions can develop during the night. Previous studies have shown that this oxygen deficiency is alleviated by the fanning behavior of mutualistic damselfish that spend the night between the coral branches, constantly moving their fins. Our findings show that fin-stroking frequency during fanning by the damselfish Dascyllus marginatus is moderately plastic, with lower frequency under higher oxygen concentration, and vice versa. The inter-play between oxygen concentration and fin motion maintains nearly steady oxygen concentration between the coral branches during the night. [ABSTRACT FROM AUTHOR]