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Purpose To evaluate the efficacy of mucoadhesive insulinloadedwhey protein (WP) /alginate (ALG) microparticles (MP)for oral insulin administration.Methods Insulin-loaded microparticles (ins-MP) made of wheyprotein and alginate were prepared by a cold gelation techniqueand an adsorption method, without adjunction of organic solventin order to develop a biocompatible vehicle for oraladministration of insulin. In vitro characterization, evaluations ofins-MP in excised intestinal tissues and hypoglycaemic effectsafter intestinal administration in healthy rats were performedResults The release properties and swelling behaviors, investigatedin different pH buffers, demonstrated a release based ondiffusion mechanism following matrix swelling. Mucoadhesionstudies in rabbits and insulin transport experiments with excisedintestinal rat tissues revealed that encapsulation in microparticleswith mucoadhesive properties promotes insulin absorption acrossduodenal membranes and bioactivity protection. In vivo experimentsreinforced the interest of encapsulation in whey protein/alginate combination. Confocal microscopic observations associatedwith blood glucose levels bring to light duodenal absorptionof insulin biologically active following in vivo administration.Conclusions Insulin-loaded WP/ALG MP with high quantities ofdrug entrapped, in vitromatrix swelling and protective effect as wellas excellent mucohadesive properties was developped. Improvementof intestinal delivery of insulin and increased in bioavailabilitywere recorded.

The assimilation of data from Earth observation satellites into numerical models is considered to be the path forward to estimate snow cover distribution in mountain catchments, providing accurate information on the mountainous snow water equivalent (SWE). The land surface temperature (LST) can be observed from space, but its potential to improve SWE simulations remains underexplored. This is likely due to the insufficient temporal or spatial resolution offered by the current thermal infrared (TIR) missions. However, three planned missions will provide global-scale TIR data at much higher spatiotemporal resolution in the coming years.To investigate the value of TIR data to improve SWE estimation, we developed a synthetic data assimilation (DA) experiment at five snow-dominated sites covering a latitudinal gradient in the Northern Hemisphere. We generated synthetic true LST and SWE series by forcing an energy balance snowpack model with the ERA5-Land reanalysis. We used this synthetic true LST to recover the synthetic true SWE from a degraded version of ERA5-Land. We defined different observation scenarios to emulate the revisiting times of Landsat 8 (16 d) and the Thermal infraRed Imaging Satellite for High-resolution Natural resource Assessment (TRISHNA) (3 d) while accounting for cloud cover. We replicated the experiments 100 times at each experimental site to assess the robustness of the assimilation process with respect to cloud cover under both revisiting scenarios. We performed the assimilation using two different approaches: a sequential scheme (particle filter) and a smoother (particle batch smoother).The results show that LST DA using the smoother reduced the normalized root mean square error (nRMSE) of the SWE simulations from 61 % (open loop) to 17 % and 13 % for 16 d revisit and 3 d revisit respectively in the absence of clouds. We found similar but higher nRMSE values by removing observations due to cloud cover but with a substantial increase in the standard deviation of the nRMSE of the replicates, highlighting the importance of revisiting times in the stability of the assimilation performance. The smoother largely outperformed the particle filter algorithm, suggesting that the capability of a smoother to propagate the information along the season is key to exploit LST information for snow modelling. Finally, we have compared the benefit of assimilating LST with synthetic observations of fractional snow cover area (FSCA). LST DA performed better than FSCA DA in all the study sites, suggesting that the information provided by LST is not limited to the duration of the snow season. These results suggest that the LST data assimilation has an underappreciated potential to improve snowpack simulations and highlight the value of upcoming TIR missions to advance snow hydrology

Plants adapt to different environmental conditions by constantly forming new organs in response to morphogenetic signals. Lateral roots branch from the main root in response to local auxin maxima. How a local auxin maximum translates into a robust pattern of gene activation ensuring the proper growth of the newly formed lateral root is largely unknown. Here, we demonstrate that miR390, TAS3-derived trans-acting short-interfering RNAs (tasiRNAs), and AUXIN RESPONSE FACTORS (ARFs) form an auxin-responsive regulatory network controlling lateral root growth. Spatial expression analysis using reporter gene fusions, tasi/miRNA sensors, and mutant analysis showed that miR390 is specifically expressed at the sites of lateral root initiation where it triggers the biogenesis of tasiRNAs. These tasiRNAs inhibit ARF2, ARF3, and ARF4, thus releasing repression of lateral root growth. In addition, ARF2, ARF3, and ARF4 affect auxin-induced miR390 accumulation. Positive and negative feedback regulation of miR390 by ARF2, ARF3, and ARF4 thus ensures the proper definition of the miR390 expression pattern. This regulatory network maintains ARF expression in a concentration range optimal for specifying the timing of lateral root growth, a function similar to its activity during leaf development. These results also show how small regulatory RNAs integrate with auxin signaling to quantitatively regulate organ growth during development.

Population growth and agricultural intensification are ever more demanding in water resources, and threaten their quality and quantity, especially in semi-arid and arid areas. The Sahara desert is typical of these multiple constraints and rapid changes making sustainable management of water resources a major issue. The wide regional aquifers have nearly fossil water. In contrast, alluvial aquifers associated with small wadis are recharged nearly each year by the rare floods. In the case of Wadi Tamanrasset, in southern Algeria, the alluvial aquifer is exploited intensively because of its accessibility and its good chemical quality. The physical conditions commanding flow and recharge of groundwater, and especially the transfer from surface to groundwater, were studied by combining hydrodynamics and isotopic tracers (18O, 2H). Monthly monitoring of groundwater level in around thirty wells was complemented by automatic recorders with hourly time steps since March 2016 in three wells, along a 600 m transect perpendicular to the wadi bed. The slow response of the water table is visible only two months after the first flood; its maximum rise was 1 m in 2016. Isotopic analyses of rainwater on a daily time scale, of the wadi water on a 1 h time scale during runoff and of groundwater (two complete campaigns in the dry and wet seasons and a specific monitoring of the transect every month) have provided additional information on surface-groundwater transfer.

Understanding the environmental drivers of interactions between predators and humans is critical for public safety and management purposes. In the marine environment, this issue is exemplified by shark-human interactions. The annual shark bite incidence rate (SBIR) in La Réunion (Indian Ocean) is among the highest in the world (up to 1 event per 24,000 hours of surfing) and has experienced a 23-fold increase over the 2005-2016 period. Since 1988, 86% of shark bite events on surfers involved ocean-users off the leeward coast, where 96% of surfing activities took place. We modeled the SBIR as a function of environmental variables, including benthic substrate, sea temperature and period of day. The SBIR peaked in winter, during the afternoon and dramatically increased on coral substrate since the mid-2000s. Seasonal patterns of increasing SBIR followed similar fluctuations of large coastal shark occurrences (particularly the bull shark Carcharhinus leucas), consistent with the hypothesis that higher shark presence may result in an increasing likelihood of shark bite events. Potential contributing factors and adaptation of ocean-users to the increasing shark bite hazard are discussed. This interdisciplinary research contributes to a better understanding of shark-human interactions. The modeling method is relevant for wildlife hazard management in general.

SARS-CoV-2 is a rapidly spreading disease affecting human life and the economy on a global scale. The disease has caused so far more then 5.5 million deaths. The omicron outbreak that emerged in Botswana in the south of Africa spread around the globe at further increased rates, and caused unprecedented SARS-CoV-2 infection incidences in several countries. At the start of December 2021 the first omicron cases were reported in France. In this paper we investigate the spreading potential of this novel variant relatively to the delta variant that was also in circulation in France at that time. Using a dynamic multi-variant model accounting for cross-immunity through a status-based approach, we analyze screening data reported by Santé Publique France over 13 metropolitan French regions between 1st of December 2021 and the 30th of January 2022. During the investigated period, the delta variant was replaced by omicron in all metropolitan regions in approximately three weeks. The analysis conducted retrospectively allows us to consider the whole replacement time window and compare regions with different times of omicron introduction and baseline levels of variants' transmission potential. As large uncertainties regarding cross-immunity among variants persist, uncertainty analyses were carried out to assess its impact on our estimations. Assuming that 80% of the population was immunized against delta, a cross delta/omicron cross-immunity of 25% and an omicron generation time of 3.5 days, the relative strength of omicron to delta, expressed as the ratio of their respective reproduction rates, [formula omitted], was found to range between 1.51 and 1.86 across regions. Uncertainty analysis on epidemiological parameters led to [formula omitted] ranging from 1.57 to 2.34 on average over the metropolitan French regions, weighted by population size. Upon introduction, omicron spread rapidly through the French territory and showed a high fitness relative to delta. We documented considerable geographical heterogeneities on the spreading dynamics. The historical reconstruction of variant emergence dynamics provide valuable ground knowledge to face future variant emergence events.

A highly multiplexed liquid chromatography mass spectrometry–multiple reaction monitoring (MRM)-based assay has been developed for evaluating 107 candidate immune biomarkers in both hemocytes and plasma of the zebra mussel Dreissena polymorpha. The Scout-MRM strategy was employed for the first time, shortening the implementation of a targeted MRM bottom-up proteomics assay using selected immune protein-related peptides identified by shotgun discovery proteogenomics. This strategy relies on spiking scout peptides during the discovery phase and using them to build and deploy the MRM targeted proteomics method. It proved to be highly relevant, since about 90% of the targeted peptides and proteins were monitored and rapidly measured in both hemocyte and plasma samples. The sample preparation protocol was optimized by evaluating the digestion efficiency of tryptic peptides over time. The accuracy and precision of 50 stable isotope-labeled peptides were evaluated for use as internal standards. Finally, the specificity of the transitions was thoroughly assessed to ensure the reliable measurement of protein biomarkers. Several analytical and biological validation criteria were evaluated across hemocytes and plasma samples exposed ex vivo to biological contaminants, resulting in the validation of two Scout-MRM assays for the relative quantitation of 85 and 89 proteins in hemocytes and plasma, respectively.

Immunoglobulin (Ig) E-mediated pathophysiological mechanisms are common in allergic diseases including severe allergic asthma (SAA). The anti-IgE monoclonal antibody omalizumab may be particularly beneficial for patients with SAA and multiple allergic comorbidities (AC) including perennial/seasonal rhinitis, conjunctivitis, atopic dermatitis (AD), and food allergy. We conducted a post-hoc analysis of the patients from the STELLAIR study (n=872, 149 minors and 723 adults). The patients were classified based on the presence of multiple AC (≥3 AC or <3 AC) or AD as assessed by questionnaire. Response to omalizumab was assessed after 4-6 months (T ) and after 12 months (T ). Asthma response at T was based on global evaluation of treatment effectiveness, reduction of ≥40% in annual exacerbation rate, and a combination of both. Asthma response at T was based on change in yearly exacerbation and hospitalization rates. AC improvement at T was based on patient perception. Patients with ≥3 AC demonstrated a higher combined response to omalizumab (74.7% vs 58.3%) at T and had reduced yearly exacerbation and hospitalization rates (88.9% vs 77.4% and -94.0% vs -70.5%, respectively). Patients with ≥3 AC were more likely to show an improvement in their AC (85.3% vs 51.9%) at T . Results were similar in minors and adults. The presence of AD was associated with greater omalizumab effectiveness at T and a greater AC improvement at T . Improvement of AD and food allergies at T were 73.2% and 38.7%, respectively, in the population overall. This post-hoc analysis of the STELLAIR study shows that omalizumab is beneficial for all SAA patients and especially for patients with multiple AC or AD. In patients with ≥3 AC, omalizumab also improved AC outcomes.

In RNA silencing, small RNAs produced by the RNase-III Dicer guide Argonaute-like proteins as part of RNA-induced silencing complexes (RISC) to regulate gene expression transcriptionally or post-transcriptionally. Here, we have characterized the RNA silencing machinery and exhaustive small RNAome of Toxoplasma gondii, member of the Apicomplexa, a phylum of animal- and human-infecting parasites that cause extensive health and economic damages to human populations worldwide. Remarkably, the small RNA-generating machinery of Toxoplasma is phylogenetically and functionally related to that of plants and fungi, and accounts for an exceptionally diverse array of small RNAs. This array includes conspicuous populations of repeat-associated small interfering RNA (siRNA), which, as in plants, likely generate and maintain heterochromatin at DNA repeats and satellites. Toxoplasma small RNAs also include many microRNAs with clear metazoan-like features whose accumulation is sometimes extremely high and dynamic, an unexpected finding given that Toxoplasma is a unicellular protist. Both plant-like heterochromatic small RNAs and metazoan-like microRNAs bind to a single Argonaute protein, Tg-AGO. Toxoplasma miRNAs co-sediment with polyribosomes, and thus, are likely to act as translational regulators, consistent with the lack of catalytic residues in Tg-AGO. Mass spectrometric analyses of the Tg-AGO protein complex revealed a common set of virtually all known RISC components so far characterized in human and Drosophila, as well as novel proteins involved in RNA metabolism. In agreement with its loading with heterochromatic small RNAs, Tg-AGO also associates substoichiometrically with components of known chromatin-repressing complexes. Thus, a puzzling patchwork of silencing processor and effector proteins from plant, fungal and metazoan origin accounts for the production and action of an unsuspected variety of small RNAs in the single-cell parasite Toxoplasma and possibly in other apicomplexans. This study establishes Toxoplasma as a unique model system for studying the evolution and molecular mechanisms of RNA silencing among eukaryotes.