Binding of malonate to the inner membrane of rat liver mitochondria

The binding of malonate to the external face of the mitochondrial inner membrane has been investigated by using mitoplasts and on the opposite face, by using inside-out oriented vesicles prepared from sonicated mitoplasts. The external face of the inner membrane displays a single class of binding sites whereas two classes are observed in vesicles. In trypsin treated vesicles, only high-affinity sites are evidenced. The disappearance of the low affinity sites is correlatively related with the loss of succinate dehydrogenase activity. Both high-affinity sites of mitoplasts and vesicles are sensitive to the presence of malate; they are also masked by 2-butylmalonate, phosphate, citrate and mercurials. Our results suggest that the internal and external high-affinity sites of the inner membrane are involved in the dicarboxylate transport system.     

The serum thymic factor (FTS)

Summary The thymus produces a nonapeptide capable of inducing T cell surface markers and T cell functions in immature lymphoid cells. This peptide is found partly bound to a carrier protein in the circulation from where it has been isolated (hence its name of serum thymic factor (FTS)). Immunofluorescence studies using an antibody raised against synthetic FTS has shown that it is produced by the thymic epithelium. Its mode of action at the cellular level involves the binding to specific high affinity receptors.     

Ulcerative skin lesions among children in Cameroon: It is not always Yaws

Outbreaks of yaws-like ulcerative skin lesions in children are frequently reported in tropical and sub-tropical countries. The origin of these lesions might be primarily traumatic or infectious; in the latter case, Treponema pallidum subspecies pertenue, the yaws agent, and Haemophilus ducreyi, the agent of chancroid, are two of the pathogens commonly associated with the aetiology of skin ulcers. In this work, we investigated the presence of T. p. pertenue and H. ducreyi DNA in skin ulcers in children living in yaws-endemic regions in Cameroon.Skin lesion swabs were collected from children presenting with yaws-suspected skin lesions during three outbreaks, two of which occurred in 2017 and one in 2019. DNA extracted from the swabs was used to amplify three target genes: the human β₂-microglobulin gene to confirm proper sample collection and DNA extraction, the polA gene, highly conserved among all subspecies of T. pallidum, and the hddA gene of H. ducreyi. A fourth target, the tprL gene was used to differentiate T. p. pertenue from the other agents of human treponematoses in polA-positive samples. A total of 112 samples were analysed in this study. One sample, negative for β₂-microglobulin, was excluded from further analysis. T. p. pertenue was only detected in the samples collected during the first 2017 outbreak (12/74, 16.2%). In contrast, H. ducreyi DNA could be amplified from samples from all three outbreaks (outbreak 1: 27/74, 36.5%; outbreak 2: 17/24, 70.8%; outbreak 3: 11/13, 84.6%). Our results show that H. ducreyi was more frequently associated to skin lesions in the examined children than T. p. pertenue, but also that yaws is still present in Cameroon. These findings strongly advocate for a continuous effort to determine the aetiology of ulcerative skin lesions during these recurring outbreaks, and to inform the planned mass treatment campaigns to eliminate yaws in Cameroon.     

Diversity of total and active free-living vs. particle-attached bacteria in the euphotic zone of the NW Mediterranean Sea

The structure of the total and metabolically active communities of attached and free-living bacteria were analysed in the euphotic zone in the NW Mediterranean Sea with the use of DNA- and RNA-derived capillary electrophoresis single-strand conformation polymorphism fingerprinting. More than half (between 52% and 69%) of the DNA-derived operational taxonomic units (OTUs) were common in both attached and free-living fractions in the euphotic layer, suggesting an exchange or co-occurrence between them. However, analysis targeting 16S rRNA showed that only some of them were found in the dominant active bacterial pool. Especially at the deep chlorophyll maximum, less than half of the attached bacterial populations were found to be active, with regard to the high proportion of OTUs present at the DNA level, but not at the RNA level. These results suggest that even if colonization on and detachment of particles appear to be ubiquitous, most of the particulate organic carbon remineralization appeared to be mediated by a rather low number of dominant active OTUs specialized in exploiting such specific microenvironment.     

Fragment-based discovery of focal adhesion kinase inhibitors

Chemically diverse fragment hits of focal adhesion kinase (FAK) were discovered by surface plasmon resonance (SPR) screening of our in-house fragment library. Site specific binding of the primary hits was confirmed in a competition setup using a high-affinity ATP-site inhibitor of FAK. Protein crystallography revealed the binding mode of 41 out of 48 selected fragment hits within the ATP-site. Structural comparison of the fragment binding modes with a DFG-out inhibitor of FAK initiated first synthetic follow-up optimization leading to improved binding affinity.     

Dissecting the oligonucleotide binding properties of a disordered chaperone protein using surface plasmon resonance

We have used surface plasmon resonance to investigate the nucleic acid binding properties of the core protein of hepatitis C virus, a disordered protein believed to chaperone the genomic RNA. It was previously shown that a peptide (peptide E) corresponding to the association of two basic clusters of core enhances the annealing and the dimerization of nucleic acid fragments derived from a stem loop (SL2) in the 3′ untranslated region of the hepatitis C virus genome. However, strong aggregation of nucleic acids by core or peptide E in the excess of the latter precluded the characterization of their binding parameters up to now. By careful design of surface plasmon resonance experiments, we obtained accurate binding parameters for the interaction of peptide E with SL2-derived oligonucleotides of different lengths and sequences, in form of stem-loop, duplex or strand. Peptide E was found to bind in a salt dependent manner to all oligonucleotides assayed. Affinity data identify at least two binding modes, of which one is independent of sequence/structure, and the other is specific to the SL2 stem-loop fold. Stoichiometry data support a multi-motif binding model allowing formation of higher-order complexes. We propose that the modular binding mode demonstrated for structured RNA-binding proteins also applies to this disordered chaperone and is relevant to its activity.     

Piagetian object-permanence in Cebus capucinus,Lagothrica flavicauda and Pan troglodytes

Object-permanence was studied with one chimpanzee (Pan troglodytes) and two New World monkeys (Lagothrica flavicauda and Cebus capucinus). The chimpanzee and the capucinus attained stage VI, while Lagothrica reached stage Va. The data show that tests of object-permanence are suitable for comparison among species. This study also attempts to propose an experimental scheme that could allow for a more valid comparison among species. Use of an operant conditioning procedure is suggested and discussed.     

Delineating reef fish trophic guilds with global gut content data synthesis and phylogeny

Understanding species’ roles in food webs requires an accurate assessment of their trophic niche. However, it is challenging to delineate potential trophic interactions across an ecosystem, and a paucity of empirical information often leads to inconsistent definitions of trophic guilds based on expert opinion, especially when applied to hyperdiverse ecosystems. Using coral reef fishes as a model group, we show that experts disagree on the assignment of broad trophic guilds for more than 20% of species, which hampers comparability across studies. Here, we propose a quantitative, unbiased, and reproducible approach to define trophic guilds and apply recent advances in machine learning to predict probabilities of pairwise trophic interactions with high accuracy. We synthesize data from community-wide gut content analyses of tropical coral reef fishes worldwide, resulting in diet information from 13,961 individuals belonging to 615 reef fish. We then use network analysis to identify 8 trophic guilds and Bayesian phylogenetic modeling to show that trophic guilds can be predicted based on phylogeny and maximum body size. Finally, we use machine learning to test whether pairwise trophic interactions can be predicted with accuracy. Our models achieved a misclassification error of less than 5%, indicating that our approach results in a quantitative and reproducible trophic categorization scheme, as well as high-resolution probabilities of trophic interactions. By applying our framework to the most diverse vertebrate consumer group, we show that it can be applied to other organismal groups to advance reproducibility in trait-based ecology. Our work thus provides a viable approach to account for the complexity of predator–prey interactions in highly diverse ecosystems.

The diversity of life on our planet has produced a remarkable variety of biological traits that characterize different species, and such traits are widely considered an alternative to taxonomy to increase our understanding of biodiversity and ecosystem functioning. This study presents an unbiased and fully reproducible framework to delineate trophic guilds in reef fishes.