In this study, to better understand the factors controlling the concentration and isotope composition of lithium (Li) in the ocean, we investigated the behaviour of Li during interaction of kaolinite ...with artificial seawater. Dissolution of kaolinite in Li-free seawater at acidic conditions (exp. 1) results in a strong preferential release of light Li isotopes, with △7Liaq-kaol ∼ −19‰, likely reflecting both the preferential breaking of 6LiO bonds over 7LiO bonds and the release of Li from the isotopically lighter AlO6 octahedral sites. Sorption experiments on kaolinite (exp. 2) revealed a partition coefficient between kaolinite and fluid of up to 28, and an isotopic fractionation of −24‰. Thermodynamic calculation indicates authigenic smectites formed from the dissolution of kaolinite in seawater at pH 8.4 (exp. 3). The formation of authigenic phase strongly removed Li from the solution (with a partition coefficient between the solid and the fluid equal to 89) and led to an increase of ca. 25‰ in seawater δ7Li. This fractionation can be described by a Rayleigh fractionation model at the early stage of the experiment during rapid clay precipitation, followed, at longer reaction time, by equilibrium isotope fractionation during the much slower removal of aqueous Li via co-precipitation and adsorption. Both processes are consistent with a fractionation factor between the solid and the aqueous solution of ∼−20‰. These experiments have implications for interpreting the Li isotopic composition of both continental and marine waters. For instance, the preferential release of 6Li observed during kaolinite far-from-equilibrium dissolution could explain the transient enrichments in 6Li observed in soil profiles. With regard to the evolution of seawater δ7Li over geological time scales, our experimental results suggest that detrital material discharged by rivers to the ocean and ensuing “reverse chemical weathering” have the potential to strongly impact the isotopic signature of the ocean through the neoformation of clay minerals.
Streptomycetes are soil-dwelling, filamentous actinobacteria and represent a prominent bacterial clade inside the plant root microbiota. The ability of streptomycetes to produce a broad spectrum of ...antifungal metabolites suggests that these bacteria could be used to manage plant diseases. Here, we describe the identification of a soil
strain named AgN23 which strongly activates a large array of defense responses when applied on
leaves. AgN23 increased the biosynthesis of salicylic acid, leading to the development of
(
)
dependent necrotic lesions. Size exclusion fractionation of plant elicitors secreted by AgN23 showed that these signals are tethered into high molecular weight complexes. AgN23 mycelium was able to colonize the leaf surface, leading to plant resistance against
infection in wild-type
plants. AgN23-induced resistance was found partially compromised in salicylate, jasmonate, and ethylene mutants. Our data show that
soil bacteria can develop at the surface of plant leaves to induce defense responses and protection against foliar fungal pathogens, extending their potential use to manage plant diseases.
The
genus comprises fungal species that are pathogens on
host plants, including
and
on apple,
on sorbus and
on pear. Although the genetic structure of
populations has been investigated in detail, ...genomic features underlying these subdivisions remain poorly understood. Here, we report whole genome sequencing of 87
strains that represent each species and each population within
We present a PacBio genome assembly for the
EU-B04 reference isolate. The size of selected genomes was determined by flow cytometry, and varied from 45 to 93 Mb. Genome assemblies of
and
contain a high content of transposable elements (TEs), most of which belong to the Gypsy or Copia LTR superfamilies and have been inactivated by Repeat-Induced Point mutations. The reference assembly of
presents a mosaic structure of GC-equilibrated regions that mainly contain predicted genes and AT-rich regions, mainly composed of TEs. Six pairs of strains were identified as clones. Single-Nucleotide Polymorphism (SNP) analysis between these clones revealed a high number of SNPs that are mostly located in AT-rich regions due to misalignments and allowed determining a false discovery rate. The availability of these genome sequences is expected to stimulate genetics and population genomics research of
pathogens. Especially, it will help understanding the evolutionary history of
species that are pathogenic on different hosts, a history that has probably been substantially influenced by TEs.
Previous work has demonstrated paradoxical increases in cerebral oxygen saturation (ScO2) as blood pressure decreases and paradoxical decreases in ScO2 as blood pressure increases. It has been ...suggested that these paradoxical responses indicate a functional cerebral autoregulation mechanism. Accordingly, the authors hypothesized that if this suggestion is correct, paradoxical responses will occur exclusively in patients with intact cerebral autoregulation.
Thirty-four patients undergoing elective cardiac surgery were included. Cerebral autoregulation was assessed with the near-infrared spectroscopy-derived cerebral oximetry index (COx), computed by calculating the Spearman correlation coefficient between mean arterial pressure and ScO2. COx less than 0.30 was previously defined as functional autoregulation. During cardiopulmonary bypass, 20% change in blood pressure was accomplished with the use of nitroprusside for decreasing pressure and phenylephrine for increasing pressure. Effects on COx were assessed. Data were analyzed using two-way ANOVA, Kruskal-Wallis test, and Wilcoxon and Mann-Whitney U test.
Sixty-five percent of patients had a baseline COx less than 0.30, indicating functional baseline autoregulation. In 50% of these patients (n = 10), COx became highly negative after vasoactive drug administration (from -0.04 -0.25 to 0.16 to -0.63 -0.83 to -0.26 after administration of phenylephrine, and from -0.05 -0.19 to 0.17 to -0.55 -0.94 to -0.35 after administration of nitroprusside). A negative COx implies a decrease in ScO2 with increase in pressure and, conversely, an increase in ScO2 with decrease in pressure.
In this study, paradoxical changes in ScO2 after pharmacological-induced pressure changes occurred exclusively in patients with intact cerebral autoregulation, corroborating the hypothesis that these paradoxical responses might be attributable to a functional cerebral autoregulation.
The existence of a large-scale population structure was investigated in Arabidopsis thaliana by studying patterns of polymorphism in a set of 71 European accessions. We used sequence polymorphism ...surveyed in 10 fragments of approximately600 nucleotides and a set of nine microsatellite markers. Population structure was investigated using a model-based inference framework. Among the accessions studied, the presence of four groups was inferred using genetic data, without using prior information on the geographical origin of the accessions. Significant genetic isolation by geographical distance was detected at the group level, together with a geographical gradient in allelic richness across groups. These results are discussed with respect to the previously proposed scenario of postglacial colonization of Europe from putative glacial refugia. Finally, the contribution of the inferred structure to linkage disequilibrium among 171 pairs of essentially unlinked markers was also investigated. Linkage disequilibrium analysis revealed that significant associations detected in the whole sample were mainly due to genetic differentiation among the inferred groups. We discuss the implication of this finding for future association studies in A. thaliana.
Hundreds of cytotoxic natural or synthetic lipidic compounds contain chiral alkynylcarbinol motifs, but the mechanism of action of those potential therapeutic agents remains unknown. Using a genetic ...screen in haploid human cells, we discovered that the enantiospecific cytotoxicity of numerous terminal alkynylcarbinols, including the highly cytotoxic dialkynylcarbinols, involves a bioactivation by HSD17B11, a short-chain dehydrogenase/reductase (SDR) known to oxidize the C-17 carbinol center of androstan-3-alpha,17-beta-diol to the corresponding ketone. A similar oxidation of dialkynylcarbinols generates dialkynylketones, that we characterize as highly protein-reactive electrophiles. We established that, once bioactivated in cells, the dialkynylcarbinols covalently modify several proteins involved in protein-quality control mechanisms, resulting in their lipoxidation on cysteines and lysines through
addition. For some proteins, this triggers their association to cellular membranes and results in endoplasmic reticulum stress, unfolded protein response activation, ubiquitin-proteasome system inhibition and cell death by apoptosis. Finally, as a proof-of-concept, we show that generic lipidic alkynylcarbinols can be devised to be bioactivated by other SDRs, including human RDH11 and HPGD/15-PGDH. Given that the SDR superfamily is one of the largest and most ubiquitous, this unique cytotoxic mechanism-of-action could be widely exploited to treat diseases, in particular cancer, through the design of tailored prodrugs.
Aim: Establishment of ruminal bacterial community in dairy calves. Methods and results: Rumen bacterial community was analyzed on 6 calves bred according to commercial practices from day one to ...weaning at day 83 of age, using 454 16S rRNA-based pyrosequencing. Samples taken at day 1 did not produce amplicons. Analysis of data revealed a three-stage implantation process with a progressive but important shift of composition. At day 2, the bacterial community was mainly composed of Proteobacteria (70%) and Bacteroidetes (14%), and Pasteurellaceae was the dominant family (58%). The bacterial community abruptly changed between days 2 and 3, and until day 12, dominant genera were Bacteroides (21%), Prevotella (11%), Fusobacterium (5%) and Streptococcus (4%). From 15 to 83 days, when solid food intake rapidly increased, Prevotella became dominant (42%) and many genera strongly decreased or were no longer detected. A limited number of bacteria genera correlated with feed intake, rumen volatile fatty acids and enzymatic activities. Conclusion: The ruminal bacterial community is established before intake of solid food, but solid food arrival in turn shapes this community. Significance and impact of the study: This study provides insight into the establishment of calves’ rumen bacterial community and suggests a strong effect of diet.
The Venturia genus comprises fungal species that are pathogens on Rosaceae host plants, including V. inaequalis and V. asperata on apple, V. aucupariae on sorbus and V. pirina on pear. Although the ...genetic structure of V. inaequalis populations has been investigated in detail, genomic features underlying these subdivisions remain poorly understood. Here, we report whole genome sequencing of 87 Venturia strains that represent each species and each population within V. inaequalis We present a PacBio genome assembly for the V. inaequalis EU-B04 reference isolate. The size of selected genomes was determined by flow cytometry, and varied from 45 to 93 Mb. Genome assemblies of V. inaequalis and V. aucupariae contain a high content of transposable elements (TEs), most of which belong to the Gypsy or Copia LTR superfamilies and have been inactivated by Repeat-Induced Point mutations. The reference assembly of V. inaequalis presents a mosaic structure of GC-equilibrated regions that mainly contain predicted genes and AT-rich regions, mainly composed of TEs. Six pairs of strains were identified as clones. Single-Nucleotide Polymorphism (SNP) analysis between these clones revealed a high number of SNPs that are mostly located in AT-rich regions due to misalignments and allowed determining a false discovery rate. The availability of these genome sequences is expected to stimulate genetics and population genomics research of Venturia pathogens. Especially, it will help understanding the evolutionary history of Venturia species that are pathogenic on different hosts, a history that has probably been substantially influenced by TEs.
A limited understanding of the pathology underlying chronic wounds has hindered the development of effective diagnostic markers and pharmaceutical interventions. This study aimed to elucidate the ...molecular composition of various common chronic ulcer types to facilitate drug discovery strategies. We conducted a comprehensive analysis of leg ulcers (LUs), encompassing venous and arterial ulcers, foot ulcers (FUs), pressure ulcers (PUs), and compared them with surgical wound healing complications (WHCs). To explore the pathophysiological mechanisms and identify similarities or differences within wounds, we dissected wounds into distinct subregions, including the wound bed, border, and peri‐wound areas, and compared them against intact skin. By correlating histopathology, RNA sequencing (RNA‐Seq), and immunohistochemistry (IHC), we identified unique genes, pathways, and cell type abundance patterns in each wound type and subregion. These correlations aim to aid clinicians in selecting targeted treatment options and informing the design of future preclinical and clinical studies in wound healing. Notably, specific genes, such as PITX1 and UPP1, exhibited exclusive upregulation in LUs and FUs, potentially offering significant benefits to specialists in limb preservation and clinical treatment decisions. In contrast, comparisons between different wound subregions, regardless of wound type, revealed distinct expression profiles. The pleiotropic chemokine‐like ligand GPR15L (C10orf99) and transmembrane serine proteases TMPRSS11A/D were significantly upregulated in wound border subregions. Interestingly, WHCs exhibited a nearly identical transcriptome to PUs, indicating clinical relevance. Histological examination revealed blood vessel occlusions with impaired angiogenesis in chronic wounds, alongside elevated expression of genes and immunoreactive markers related to blood vessel and lymphatic epithelial cells in wound bed subregions. Additionally, inflammatory and epithelial markers indicated heightened inflammatory responses in wound bed and border subregions and reduced wound bed epithelialization. In summary, chronic wounds from diverse anatomical sites share common aspects of wound pathophysiology but also exhibit distinct molecular differences. These unique molecular characteristics present promising opportunities for drug discovery and treatment, particularly for patients suffering from chronic wounds. The identified diagnostic markers hold the potential to enhance preclinical and clinical trials in the field of wound healing.
PDF
