Although they are not often in explicit conversation with each other, several scholarly contributions about the otherwise and grace, respectively, echo each other in striking ways. In this article, ...the author explores some of these echoes. Assembling theoretically various approaches to the otherwise and grace allows him to show that they both tread on similar theopolitical paths, and to identify three points on which they converge: excess, incarnation and turbulence. The article is structured around these three confluences. Each section begins with a description of a particular way of approaching the otherwise, which is then compared with a similar way of approaching grace. Each section concludes with reflections on the spaces of convergence thus identified, and it is argued that they constitute promising sites for the deployment of a ‘theopolitical analytics’ in anthropology.
Transnational congregations are ambiguous and complex social spaces as they are both divided (notably around the North–South axis) and united (around a same charism, a same founding figure). This ...article seeks to understand how sisters from Quebec and Central America belonging to the same transnational congregation construct their interpersonal relations, given that they live in a social field marked by both North–South domination and religious sisterhood. Based on two months of fieldwork within the congregation at the Order’s mother house in Quebec and at some of its mission houses in Honduras, it explores this issue through a brief presentation of the history of the congregation and an analysis of the discourses of the sisters interviewed. It concludes that the intra-congregational relationships are rooted in the continuous negotiation between the verticality of North–South domination and the horizontality of sisterhood. In the present context of vocational decline, the congregation faces two options: to decolonize or to remain trapped in contradictions that could stop it from adapting to its new reality.
Abstract
The imipridones ONC201 and ONC212 selectively kill cancer cells and have been ascribed multiple mechanisms-of-action. Genome-wide CRISPR knockout screens revealed that loss of the ...mitochondrial proteases CLPP and MIPEP confer strong resistance to both compounds...
Systematic genetic interaction profiles can reveal the mechanisms-of-action of bioactive compounds. The imipridone ONC201, which is currently in cancer clinical trials, has been ascribed a variety of different targets. To investigate the genetic dependencies of imipridone action, we screened a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) knockout library in the presence of either ONC201 or its more potent analog ONC212. Loss of the mitochondrial matrix protease CLPP or the mitochondrial intermediate peptidase MIPEP conferred strong resistance to both compounds. Biochemical and surrogate genetic assays showed that impridones directly activate CLPP and that MIPEP is necessary for proteolytic maturation of CLPP into a catalytically competent form. Quantitative proteomic analysis of cells treated with ONC212 revealed degradation of many mitochondrial as well as nonmitochondrial proteins. Prompted by the conservation of ClpP from bacteria to humans, we found that the imipridones also activate ClpP from Escherichia coli, Bacillus subtilis, and Staphylococcus aureus in biochemical and genetic assays. ONC212 and acyldepsipeptide-4 (ADEP4), a known activator of bacterial ClpP, caused similar proteome-wide degradation profiles in S. aureus. ONC212 suppressed the proliferation of a number of Gram-positive (S. aureus, B. subtilis, and Enterococcus faecium) and Gram-negative species (E. coli and Neisseria gonorrhoeae). Moreover, ONC212 enhanced the ability of rifampin to eradicate antibiotic-tolerant S. aureus persister cells. These results reveal the genetic dependencies of imipridone action in human cells and identify the imipridone scaffold as a new entry point for antibiotic development.
BMP9 (bone morphogenetic protein 9) is a circulating endothelial quiescence factor with protective effects in pulmonary arterial hypertension (PAH). Loss-of-function mutations in BMP9, its receptors, ...and downstream effectors have been reported in heritable PAH.
To determine how an acquired deficiency of BMP9 signaling might contribute to PAH.
Plasma levels of BMP9 and antagonist soluble endoglin were measured in group 1 PAH, group 2 and 3 pulmonary hypertension (PH), and in patients with severe liver disease without PAH.
BMP9 levels were markedly lower in portopulmonary hypertension (PoPH) versus healthy control subjects, or other etiologies of PAH or PH; distinguished PoPH from patients with liver disease without PAH; and were an independent predictor of transplant-free survival. BMP9 levels were decreased in mice with PH associated with CCl
-induced portal hypertension and liver cirrhosis, but were normal in other rodent models of PH. Administration of ALK1-Fc, a BMP9 ligand trap consisting of the activin receptor-like kinase-1 extracellular domain, exacerbated PH and pulmonary vascular remodeling in mice treated with hypoxia versus hypoxia alone.
BMP9 is a sensitive and specific biomarker of PoPH, predicting transplant-free survival and the presence of PAH in liver disease. In rodent models, acquired deficiency of BMP9 signaling can predispose to or exacerbate PH, providing a possible mechanistic link between PoPH and heritable PAH. These findings describe a novel experimental model of severe PH that provides insight into the synergy between pulmonary vascular injury and diminished BMP9 signaling in the pathogenesis of PAH.
Next‐generation sequencing (NGS) is the primary method used to monitor the distribution and emergence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants around the world; ...however, it is costly and time‐consuming to perform and is not widely available in low‐resourced geographical regions. Pyrosequencing has the potential to augment surveillance efforts by providing information on specific targeted mutations for rapid identification of circulating and emerging variants. The current study describes the development of a reverse transcription (RT)‐PCR‐pyrosequencing assay targeting >65 spike protein gene (S) mutations of SARS‐CoV‐2, which permits differentiation of commonly reported variants currently circulating in the United States with a high degree of confidence. Variants typed using the assay included B.1.1.7 (Alpha), B.1.1.529 (Omicron), B.1.351 (Beta), B.1.375, B.1.427/429 (Epsilon), B.1.525 (Eta), B.1.526.1 (Iota), B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.621 (Mu), P1 (Gamma), and B.1.1 variants, all of which were confirmed by the NGS data. An electronic typing tool was developed to aid in the identification of variants based on mutations detected by pyrosequencing. The assay could provide an important typing tool for rapid identification of candidate patients for monoclonal antibody therapies and a method to supplement SARS‐CoV‐2 surveillance efforts by identification of circulating variants and novel emerging lineages.
•Climate change impacts on leaf rust of wheat are forecasted with a dynamic model.•Sub-models of microclimate and epidemic surfaces manage host-pathogen interaction.•Disease dynamics is simulated on ...3 French sites under 2.6, 4.5, 8.5 RCP scenarios.•Simulated crop-pathogen synchronism promotes disease at the end of the century.•Simulated microclimate at early wheat stages favors future disease development.
Leaf rust is responsible for significant wheat yield losses. Its occurrence and severity have increased in recent years, partly because of warmer climate. It is therefore critical to understand and anticipate the effects of climate change on leaf rust. Direct climate effects and indirect effects via host plants that provide a biophysical environment for disease development were both considered. The coupled STICS-MILA model simulates both crop and pathogen dynamics in a mechanistic way and their interaction is managed by two sub-models: one calculating the microclimate within the canopy and the other converting numbers of spores and lesions to affected surfaces. In this study, STICS-MILA was first calibrated and evaluated using leaf rust severity observed at various sites in France for multiple years. STICS-MILA was then run on three contrasting French sites under 2.6, 4.5 and 8.5 RCP future climate scenarios. Results focused firstly on changes in disease earliness and intensity, secondly on disease dynamics, particularly the synchronism between plant and disease developments, and finally on elementary epidemic processes.
The calibration and evaluation of STICS-MILA revealed a high sensitivity to the initial amount of primary inoculum (a forcing variable in STICS-MILA) and thus the need to properly simulate the summering and overwintering pathogen survival. The simulations in the context of future climate showed a significant change in host-pathogen synchronism: in the far future, according to RCP 4.5 and 8.5 scenarios, disease onset is expected to occur not only with an advance of around one month but also at an earlier developmental stage of wheat crops. This positive effect results from rising temperatures, nevertheless partly counter-balanced during spring by lower wetness frequency. The crop growth accelerates during juvenile stages, providing a greater support for disease development. The resulting microclimate shortens latency periods and increases infection and sporulation efficiencies, thus causing more infectious cycles. An increase of final disease severity is thus forecasted with climate change.
Volumetric muscle defect, caused by trauma or combat injuries, is a major health concern leading to severe morbidity. It is characterized by partial or full thickness loss of muscle and its ...bio-scaffold, resulting in extensive fibrosis and scar formation. Therefore, the ideal therapeutic option is to use stem cells combined with bio-scaffolds to restore muscle. For this purpose, muscle-derived stem cells (MDSCs) are a great candidate due to their unique multi-lineage differentiation potential.
In this study, we evaluated the regeneration potential of MDSCs for muscle loss repair using a novel in situ fibrin gel casting. Muscle defect was created by a partial thickness wedge resection in the tibialis anterior (TA) muscles of NSG mice which created an average of 25% mass loss. If untreated, this defect leads to severe muscle fibrosis. Next, MDSCs were delivered using a novel in situ fibrin gel casting method.
Our results demonstrated MDSCs are able to engraft and form new myofibers in the defect when casted along with fibrin gel. LacZ labeled MDSCs were able to differentiate efficiently into new myofibers and significantly increase muscle mass. This was also accompanied by significant reduction of fibrotic tissue in the engrafted muscles. Furthermore, transplanted cells also contributed to new vessel formation and satellite cell seeding.
These results confirmed the therapeutic potential of MDSCs and feasibility of direct in situ casting of fibrin/MDSC mixture to repair muscle mass defects.
•Severe skeletal muscle loss cannot be repaired by endogenous mechanisms leading to muscle fibrosis.•Muscle stem cells along with appropriate bio-scaffolds are considered as a potential therapeutic option in these cases.•Muscle-derived stem cells (MDSCs) are one of the best candidates for muscle loss repair due to their unique potentials.•MDSCs combined with fibrin gel casting enables successful repair of muscle loss in the mouse model of muscle defect.
•Six combinations of models offered future trends for leaf rust of wheat.•Climatic risk indicators assessed the intensity, frequency & duration of leaf rust.•Future climatic conditions in the autumn ...and winter would favor leaf rust infection.•A distinct drop should be expected in the summer enabling a longer risk-free period.
Crop fungal diseases threaten food security in the dual context of a growing global population and a warming climate. Leaf rust is one of the most important wheat diseases which can result in yield losses of more than 40 %. When considering these crucial questions, innovative approaches to crop cultivation are clearly required. One essential prerequisite before the development of adaptive strategies to climate change, is to understand and forecast the potential impact of this change on fungal diseases, based on the use of modelling approaches. However, numerous epidemiological models are available; they vary considerably in terms of their complexity, and are based on hypotheses that oversimplify factors that influence the prediction of epidemics. During this study, we implemented six combinations of leaf wetness duration and infection efficiency models to simulate the future evolution of leaf rust of wheat, and compared the resulting trends. Daily and seasonal climatic indicators were inferred from the simulated infection efficiencies, from 1950 to 2100, with two contrasted Representative Concentration Pathways, RCP 4.5 and RCP 8.5, at three sites representative of traditional French wheat production areas. The inferred indicators characterize the intensity and frequency of leaf rust infection, the length and calendar positioning of the longest sequences without infection, and the relevant microclimate. Their absolute values varied considerably depending on the model combinations used, even more than between the present and future climatic periods or RCP scenarios. However, the same trends were observed in the future, with climate change being a significant explanatory variable of the evolution of the six climatic indicators simulated. The results of combining these models showed that the climatic risk of both the frequency and intensity of leaf rust infection would increase during the autumn and winter seasons, and a distinct drop should be expected during the summer, enabling a longer risk-free period. Some important common trends were thus highlighted, reinforcing confidence in the robustness of the results. These findings should be taken into account when designing adaptive strategies that will sustain production under future abiotic stresses while minimizing sanitary risks.
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