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Abstract Growth at the shoot apical meristem (SAM) is essential for shoot architecture construction. The phytohormones gibberellins (GA) play a pivotal role in coordinating plant growth, but their role in the SAM remains mostly unknown. Here, we developed a ratiometric GA signaling biosensor by engineering one of the DELLA proteins, to suppress its master regulatory function in GA transcriptional responses while preserving its degradation upon GA sensing. We demonstrate that this degradation-based biosensor accurately reports on cellular changes in GA levels and perception during development. We used this biosensor to map GA signaling activity in the SAM. We show that high GA signaling is found primarily in cells located between organ primordia that are the precursors of internodes. By gain- and loss-of-function approaches, we further demonstrate that GAs regulate cell division plane orientation to establish the typical cellular organization of internodes, thus contributing to internode specification in the SAM.

Abstract Background The health and productivity of dairy goats continue to be impacted by gastrointestinal nematodes (GIN) and lungworms (LW). Eprinomectin (EPN) is frequently selected for treatment because it is generally effective and does not require a milk withdrawal period. However, some factors, such as lactation, can have an impact on EPN pharmacokinetics and potentially its efficacy. To evaluate whether this can alter the efficacy of Eprecis® 2%, an eprinomectin injectable solution, a study was performed in lactating goats using the dose currently registered in cattle, sheep and goats (0.2 mg/kg). Methods This study was a blinded, randomized, controlled trial performed according to the VICH guidelines. Eighteen (18) worm-free lactating goats were included and experimentally challenged on day 28 with a mixed culture of infective gastrointestinal and lung nematode larvae (Haemonchus contortus, Trichostrongylus colubriformis, Teladorsagia circumcincta, Dictyocaulus filaria). At D-1, fecal samples were collected to confirm patent infection in all animals. On D0, the goats were randomly allocated into two groups of nine goats; group 1 was treated with Eprecis® 2% at 0.2 mg/kg BW by subcutaneous injection, while group 2 remained untreated. Fecal samples for egg counts were collected from all animals on days 3, 5, 7, 9, 11 and 14. On D14, all goats were killed, and the abomasum, small intestine and lungs were removed, processed and subsampled to record the number and species of worms. Results The treatment was well tolerated. After treatment, the arithmetic mean FEC decreased in the treated group and remained < 5 EPG until the end of the study, while the arithmetic mean FEC in the control group remained > 849.0 EPG. At D14, goats in the treated group had very limited or zero total worm counts, whereas all animals from the control group had a high worm burden. The measured efficacy was 100.0% against H. contortus and T. colubriformis, 99.9% against T. circumcincta and 98.0% against D. filaria. Conclusions Eprinomectin (Eprecis®, 20 mg/ml), administered at the label dose (0.2 mg/kg), is highly effective against gastrointestinal nematodes and lungworms in lactating goats. Graphical abstract

Abstract The development of vascular networks in microfluidic chips is crucial for the long-term culture of three-dimensional cell aggregates such as spheroids, organoids, tumoroids, or tissue explants. Despite rapid advancement in microvascular network systems and organoid technologies, vascularizing organoids-on-chips remains a challenge in tissue engineering. Most existing microfluidic devices poorly reflect the complexity of in vivo flows and require complex technical set-ups. Considering these constraints, we develop a platform to establish and monitor the formation of endothelial networks around mesenchymal and pancreatic islet spheroids, as well as blood vessel organoids generated from pluripotent stem cells, cultured for up to 30 days on-chip. We show that these networks establish functional connections with the endothelium-rich spheroids and vascular organoids, as they successfully provide intravascular perfusion to these structures. We find that organoid growth, maturation, and function are enhanced when cultured on-chip using our vascularization method. This microphysiological system represents a viable organ-on-chip model to vascularize diverse biological 3D tissues and sets the stage to establish organoid perfusions using advanced microfluidics.

ABSTRACTRecycled manure solids (RMS) is used as bedding material in cow housing but can be at risk for pathogens development. Cows spend several hours per day lying down, contributing to the transfer of potential mastitis pathogens from the bedding to the udder. The effect of a bacterial conditioner (Manure Pro, MP) application was studied on RMS-bedding and milk qualities and on animal health. MP product was applied on bedding once a week for 3 months. Bedding and teat skin samples were collected from Control and MP groups at D01, D51, and D90 and analyzed through 16S rRNA amplicon sequencing. MP application modified bacterial profiles and diversity. Control bedding was significantly associated with potential mastitis pathogens, while no taxa of potential health risk were significantly detected in MP beddings. Functional prediction identified enrichment of metabolic pathways of agronomic interest in MP beddings. Significant associations with potential mastitis pathogens were mainly observed in Control teat skin samples. Finally, significantly better hygiene and lower Somatic Cell Counts in milk were observed for cows from MP group, while no group impact was observed on milk quality and microbiota. No dissemination of MP strains was observed from bedding to teats or milk.IMPORTANCEThe use of Manure Pro (MP) conditioner improved recycled manure solids-bedding quality and this higher sanitary condition had further impacts on dairy cows' health with less potential mastitis pathogens significantly associated with bedding and teat skin samples of animals from MP group. The animals also presented an improved inflammation status, while milk quality was not modified. The use of MP conditioner on bedding may be of interest in controlling the risk of mastitis onset for dairy cows and further associated costs.

The composition of clay minerals in soils, and more particularly the presence of montmorillonite (as part of the smectite family), is a key factor in soil swell–shrinking as well as off–road vehicle mobility. Detecting these topsoil clay minerals and quantifying the montmorillonite abundance are a challenge since they are usually intimately mixed with other minerals, soil organic carbon and soil moisture content. Imaging spectroscopy coupled with unmixing methods can address these issues, but the quality of the estimation degrades the coarser the spatial resolution is due to pixel heterogeneity. With the advent of UAV-borne and proximal hyperspectral acquisitions, it is now possible to acquire images at a centimeter scale. Thus, the objective of this paper is to evaluate the accuracy and limitations of unmixing methods to retrieve montmorillonite abundance from very-high-resolution hyperspectral images (1.5 cm) acquired from a camera installed on top of a bucket truck over three different agricultural fields, in Loiret department, France. Two automatic endmember detection methods based on the assumption that materials are linearly mixed, namely the Simplex Identification via Split Augmented Lagrangian (SISAL) and the Minimum Volume Constrained Non-negative Matrix Factorization (MVC-NMF), were tested prior to unmixing. Then, two linear unmixing methods, the fully constrained least square method (FCLS) and the multiple endmember spectral mixture analysis (MESMA), and two nonlinear unmixing ones, the generalized bilinear method (GBM) and the multi-linear model (MLM), were performed on the images. In addition, several spectral preprocessings coupled with these unmixing methods were applied in order to improve the performances. Results showed that our selected automatic endmember detection methods were not suitable in this context. However, unmixing methods with endmembers taken from available spectral libraries performed successfully. The nonlinear method, MLM, without prior spectral preprocessing or with the application of the first Savitzky–Golay derivative, gave the best accuracies for montmorillonite abundance estimation using the USGS library (RMSE between 2.2–13.3% and 1.4–19.7%). Furthermore, a significant impact on the abundance estimations at this scale was in majority due to (i) the high variability of the soil composition, (ii) the soil roughness inducing large variations of the illumination conditions and multiple surface scatterings and (iii) multiple volume scatterings coming from the intimate mixture. Finally, these results offer a new opportunity for mapping expansive soils from imaging spectroscopy at very high spatial resolution.

ABSTRACT Urinary tract infections (UTIs) are one of the most common bacterial infections in humans, with ~400 million cases across the globe each year. Uropathogenic Escherichia coli (UPEC) is the major cause of UTI and increasingly associated with antibiotic resistance. This scenario has been worsened by the emergence and spread of pandemic UPEC sequence type 131 (ST131), a multidrug-resistant clone associated with extraordinarily high rates of infection. Here, we employed transposon-directed insertion site sequencing in combination with metabolomic profiling to identify genes and biochemical pathways required for growth and survival of the UPEC ST131 reference strain EC958 in human urine (HU). We identified 24 genes required for growth in HU, which mapped to diverse pathways involving small peptide, amino acid and nucleotide metabolism, the stringent response pathway, and lipopolysaccharide biosynthesis. We also discovered a role for UPEC resistance to fluoride during growth in HU, most likely associated with fluoridation of drinking water. Complementary nuclear magnetic resonance (NMR)-based metabolomics identified changes in a range of HU metabolites following UPEC growth, the most pronounced being L-lactate, which was utilized as a carbon source via the L-lactate dehydrogenase LldD. Using a mouse UTI model with mixed competitive infection experiments, we demonstrated a role for nucleotide metabolism and the stringent response in UPEC colonization of the mouse bladder. Together, our application of two omics technologies combined with different infection-relevant settings has uncovered new factors required for UPEC growth in HU, thus enhancing our understanding of this pivotal step in the UPEC infection pathway.IMPORTANCEUropathogenic Escherichia coli (UPEC) cause ~80% of all urinary tract infections (UTIs), with increasing rates of antibiotic resistance presenting an urgent threat to effective treatment. To cause infection, UPEC must grow efficiently in human urine (HU), necessitating a need to understand mechanisms that promote its adaptation and survival in this nutrient-limited environment. Here, we used a combination of functional genomic and metabolomic techniques and identified roles for the metabolism of small peptides, amino acids, nucleotides, and L-lactate, as well as the stringent response pathway, lipopolysaccharide biosynthesis, and fluoride resistance, for UPEC growth in HU. We further demonstrated that pathways involving nucleotide metabolism and the stringent response are required for UPEC colonization of the mouse bladder. The UPEC genes and metabolic pathways identified in this study represent targets for the development of innovative therapeutics to prevent UPEC growth during human UTI, an urgent need given the rapidly rising rates of global antibiotic resistance.

In the past decade, stereotactic body radiation therapy (SBRT) has emerged as a valid treatment option for patients with localized prostate cancer. Despite the promising results of ultra-hypofractionation in terms of tolerance and disease control, the toxicity profile of SBRT for prostate cancer patients with a history of surgical treatment of benign prostate hyperplasia is still underreported. Here we present an overview of the available data on urinary morbidity for prostate cancer patients treated with SBRT after prior surgical treatments for benign prostate hyperplasia. Technical improvements useful to minimize toxicity and possible treatments for radiation-induced urethritis are discussed.

Introduction Fast and accurate diagnosis of acute stroke is crucial to timely initiate reperfusion therapies. Conventional high-field (HF) MRI yields the highest accuracy in discriminating early ischaemia from haemorrhages and mimics. Rapid access to HF-MRI is often limited by contraindications or unavailability. Low-field (LF) MRI (

Les anticorps thérapeutiques font désormais partie intégrante de l'arsenal médical dans le traitement de nombreuses affections, y compris en hémostase. Ce sont tous des anticorps monoclonaux humanisés – au suffixe "zumab" – permettant de restaurer partiellement l'hémostase (emicizumab, concizumab), ou ayant une action d'antidote (idarucizumab) pour antagoniser l'effet de certains anticoagulants (dabigatran) ou des antiagrégants plaquettaires (bentracimab encore à l'étude) ; d'autres ont été ou pourront être utilisés pour leur propre pouvoir antiagrégant (abciximab arrêté en septembre 2019 ou le futur antiagrégant antiGPVI, glencozimab). Le caplacizumab est quant à lui un nanobody indiqué dans la phase aiguë du purpura thrombotique thrombocytopénique acquis. Therapeutic antibodies are now an integral part of the therapeutic arsenal in the treatment of many conditions, including haemostasis. They are all humanized monoclonal antibodies (suffix : zumab) that can partially restore hemostasis (emicizumab, concizumab), or used as an antidote (idarucizumab) to antagonize the effect of certain anticoagulant (dabigatran) or platelet antiagregants (bentra-cimab, still under study). Others therapeutic antibodies have been or may be used for their own antiagregant properties (abciximab, discontinued in September 2019, or the future anti-GPVI antiagregant glencozimab, still under study). As for caplacizumab, it is a nanobody indicated in the acute phase of acquired throm-botic thrombocytopenic purpura. [ABSTRACT FROM AUTHOR]

Deep learning algorithms have been widely used for cardiac image segmentation. However, most of these architectures rely on convolutions that hardly model long-range dependencies, limiting their ability to extract contextual information. Moreover, the traditional U-net architecture suffers from the difference of semantic information between feature maps of the encoder and decoder (also known as the semantic gap). To address this issue, a new network architecture relying on attention mechanism was introduced. Swin Filtering Blocks (SFB), that use Swin Transformer blocks in a cross-attention manner, were added between the encoder and the decoder to filter information coming from the encoder based on the feature map from the decoder. Attention was also employed at the lowest resolution in the form of a transformer layer to increase the receptive field of the network. We conducted experiments to assess both generalization capability and to evaluate how training on all frames of the cardiac cycle rather than only the end-diastole and end-systole impacts strain and segmentation performances. Visual inspection of feature maps suggested that Swin Filtering Blocks contribute to the reduction of the semantic gap. Performing attention between all patches using a transformer layer brought higher performance than convolutions. Training the model with all phases of the cardiac cycle resulted in slightly more accurate segmentations while leading to a more noticeable improvement for strain estimation. A limited decrease in performance was observed when testing on out-of-distribution data, but the gap widens for the most apical slices. • Neural network architecture relying on attention to bridge the semantic gap. • Tested on both ACDC and an in-house dataset containing 271 patients. • Generalization capabilities assessed by testing on out-of-distribution data. • Comparison between training on all cardiac phases or only on ED and ES frames. • State of the art performance and accurate volumetric indices are obtained. [ABSTRACT FROM AUTHOR]

Growth at the shoot apical meristem (SAM) is essential for shoot architecture construction. The phytohormones gibberellins (GA) play a pivotal role in coordinating plant growth, but their role in the SAM remains mostly unknown. Here, we developed a ratiometric GA signaling biosensor by engineering one of the DELLA proteins, to suppress its master regulatory function in GA transcriptional responses while preserving its degradation upon GA sensing. We demonstrate that this degradation-based biosensor accurately reports on cellular changes in GA levels and perception during development. We used this biosensor to map GA signaling activity in the SAM. We show that high GA signaling is found primarily in cells located between organ primordia that are the precursors of internodes. By gain- and loss-of-function approaches, we further demonstrate that GAs regulate cell division plane orientation to establish the typical cellular organization of internodes, thus contributing to internode specification in the SAM., (© 2024. The Author(s).)

ANT3310 is a novel broad-spectrum diazabicyclooctane serine β-lactamase inhibitor being developed in combination with meropenem (MEM) for the treatment of serious infections in hospitalized patients where carbapenem-resistant Gram-negative pathogens are expected. In this study, we evaluated the in vitro antibacterial activity of MEM in the presence of ANT3310 at 8 µg/mL against global clinical isolates that included Acinetobacter baumannii ( n = 905), carbapenem-resistant Enterobacterales (CRE), carrying either oxacillinase (OXA) ( n = 252) or Klebsiella pneumoniae carbapenemase (KPC) ( n = 180) carbapenemases, and Pseudomonas aeruginosa ( n = 502). MEM was poorly active against A. baumannii, as were MEM-vaborbactam, ceftazidime-avibactam, aztreonam-avibactam, cefepime-taniborbactam, cefepime-zidebactam, and imipenem-relebactam (MIC 90 values of ≥32 µg/mL). On the other hand, MEM-ANT3310 displayed an MIC 90 value of 4 µg/mL, similar to that observed with sulbactam-durlobactam, a drug developed to specifically treat A. baumannii infections. ANT3310 (8 µg/mL) additionally restored the activity of MEM against OXA- and KPC-producing CREs decreasing MEM MIC 90 values from >32 µg/mL to 0.25 and 0.5 µg/mL, respectively. The combination of 8 µg/mL of both MEM and ANT3310 prevented growth of 97.5% of A. baumannii and 100% of OXA- and KPC-positive CREs, with ~90% of P. aeruginosa isolates also displaying MEM MICs ≤8 µg/mL. Furthermore, MEM-ANT3310 was efficacious in both thigh and lung murine infection models with OXA-23 A. baumannii . This study demonstrates the potent in vitro activity of the MEM-ANT3310 combination against both carbapenem-resistant A. baumannii and Enterobacterales clinical isolates, a key differentiator to other β-lactam/β-lactamase combinations., Competing Interests: ANTABIO SAS paid for most of the studies presented in this manuscript. M.Z., P.A., A.L., D.D., S.L., C.S., A.L., J.B., J.C., C.L.,M.E., and M.L. were ANTABIO employees at the time this work was performed.