Interfertility between Armillaria cepistipes and A. sinapina

Des études ont rapporté que des lignées européennes d'Armillaria cepistipes étaient interfertiles avec trois lignées américaines d'Armillaria désignées par les termes espèce biologique nord-américaine (NABS) V (A sinapina), NABS X et NABS XI. Une telle interfertilité entre les espèces soulève des doutes au sujet de l'utilisation de binômes latins distincts pour des espèces pouvant se reproduire. Cette interfertilité a été ré-examinée en mettant 24 isolats haploïdes d'A cepistipes européen en présence de 23 isolats 6'A. sinapina d'Amérique du Nord et d'Asie. Les appariements individuels ont été effectués de façon indépendante au moins une fois à l'Université Laval (Canada) et à NNRA Clermont-Ferrand (France). Des 420 appariements interspécifiques effectués à l'Université Laval, deux étaient positifs et sept étaient ambigus, pour un total de 2,1 % de tous les appariements. Des 506 appariements effectués à Clermont-Ferrand, 10 étaient positifs et 24 étaient ambigus pour un total de 6,7 % des appariements. Les différences dans les résultats de ces appariements peuvent être expliquées par les températures d'incubation, ainsi que par les différents types et concentrations d'extrait de malt utilisés dans chaque laboratoire. Les bas niveaux d'interfertilité trouvés entre A cepistipes et A. sinapina peuvent résulter de l'absence de barrières génétiques habituellement présentes entre des espèces sympatriques. Ce bas niveau d'interfertilité reflète des différences entre la morphologie, la répartition et les habitats des deux espèces d'Armillaria, et appuie la conservation de dénominations d'espèces distinctes.European strains of Armillaria cepistipes were reported to be interfertile with strains from three American Armillaria species known as North American Biological Species (NABS) V (A sinapina), NABS X and NABS XI. Such interfertility between species raises some doubts about using different Latin binomials for species capable of mating. This interfertility was reinvestigated by mating 24 haploid isolates of European A cepistipes with 23 isolates of A sinapinafrom North America and Asia. Individual pairings were independently performed at least once at Universite Laval, Canada and at INRA Clermont-Ferrand, France. From the 420 interspecific pairings performed at Laval, two were positive and seven were ambiguous for a total of 2.1% of all the pairings. From the 506 pairings made at Clermont-Ferrand, 10 were positive and 24 were ambiguous for a total of 6.7%. The differences in the pairing results may be explained by incubation temperatures, and the different types and concentrations of malt extract used at each laboratory. The low levels of interfertility found between A. cepistipes and A. sinapina may result from the absence of genetic barriers that are usually present between sympatric species. This low level of interfertility reflects differences in morphology, distribution, and habitat for these two species of Armillaria and this supports the retention of different species denominations

The Use of Isomeric Testosterone Dimers to Explore Allosteric Effects in Substrate Binding to Cytochrome P450 CYP3A4

Abstract: Cytochrome P450 CYP3A4 is the main drug-metabolizing enzyme in the human liver, being responsible for oxidation of 50% of all pharmaceuticals metabolized by human P450 enzymes. Possessing a large substrate binding pocket, it can simultaneously bind several substrate molecules and often exhibits a complex pattern of drug–drug interactions. In order to better understand structural and functional aspects of binding of multiple substrate molecules to CYP3A4 we used resonance Raman and UV–VIS spectroscopy to document the effects of binding of synthetic testosterone dimers of different configurations, cis-TST2 and trans-TST2. We directly demonstrate that the binding of two steroid molecules, which can assume multiple possible configurations inside the substrate binding pocket of monomeric CYP3A4, can lead to active site structural changes that affect functional properties. Using resonance Raman spectroscopy, we have documented perturbations in the ferric and Fe-CO states by these substrates, and compared these results with effects caused by binding of monomeric TST. While the binding of trans-TST2 yields results similar to those obtained with monomeric TST, the binding of cis-TST2 is much tighter and results in significantly more pronounced conformational changes of the porphyrin side chains and Fe-CO unit. In addition, binding of an additional monomeric TST molecule in the remote allosteric site significantly improves binding affinity and the overall spin shift for CYP3A4 with trans-TST2 dimer bound inside the substrate binding pocket. This result provides the first direct evidence for an allosteric effect of the peripheral binding site at the protein-membrane interface on the functional properties of CYP3A4. Graphical abstract: Synthetic dimers of the steroid testosterone are used to address directly the mechanisms of multiple substrate binding at the active site of cytochrome P450 3A4 and the role of substrate binding at a distal site in the control of allostery in this central enzyme of human drug metabolism

Effects of a healthy meal course on spontaneous energy intake, satiety and palatability

Many food components can influence satiety or energy intake. Combined together, these food components could represent an interesting dietary strategy in the prevention and treatment of obesity. The aims of this study were: 1) to determine the effect of a functional food in the form of a healthy meal course on subsequent energy intake and satiety; 2) to verify if it is possible to maintain palatability while preserving the satiating effects of the test meal. Thirteen subjects were invited to eat two lunch sessions: healthy and control meal courses (2090 kJ/meal). Anthropometric and ad libitum food intake measurements, and visual analogue scales (VAS) were performed during the two lunch sessions. The healthy main course acutely decreased energy intake during the rest of the meal ( − 744 kJ, P ≤ 0·0001) and lipid ( − 6 %, P ≤ 0·0001) compared with the control meal. VAS ratings during the course of the testing showed a meal effect for hunger, desire to eat and prospective food consumption (P ≤ 0·05) and a time effect for all appetite sensations (P ≤ 0·0001). VAS scores on hunger ratings were lower for the healthy meal (P ≤ 0·05), whereas fullness ratings were higher shortly after the healthy main course (P ≤ 0·05). The healthy meal produced a slightly higher palatability rating but this effect was not statistically significant. These results suggest that it is possible to design a healthy meal that decreases spontaneous energy intake and hunger without compromising palatability

Invariant vector fields and the prolongation method for supersymmetric quantum systems

The kinematical and dynamical symmetries of equations describing the time evolution of quantum systems like the supersymmetric harmonic oscillator in one space dimension and the interaction of a non-relativistic spin one-half particle in a constant magnetic field are reviewed from the point of view of the vector field prolongation method. Generators of supersymmetries are then introduced so that we get Lie superalgebras of symmetries and supersymmetries. This approach does not require the introduction of Grassmann valued differential equations but a specific matrix realization and the concept of dynamical symmetry. The Jaynes-Cummings model and supersymmetric generalizations are then studied. We show how it is closely related to the preceding models. Lie algebras of symmetries and supersymmetries are also obtained.Comment: 37 pages, 7 table

Histone deacetylase 1 and 2 drive differentiation and fusion of progenitor cells in human placental trophoblasts

Cell fusion occurs when several cells combine to form a multinuclear aggregate (syncytium). In human placenta, a syncytialized trophoblast (syncytiotrophoblast) layer forms the primary interface between maternal and fetal tissue, facilitates nutrient and gas exchange, and produces hormones vital for pregnancy. Syncytiotrophoblast development occurs by differentiation of underlying progenitor cells called cytotrophoblasts, which then fuse into the syncytiotrophoblast layer. Differentiation is associated with chromatin remodeling and specific changes in gene expression mediated, at least in part, by histone acetylation. However, the epigenetic regulation of human cytotrophoblast differentiation and fusion is poorly understood. In this study, we found that human syncytiotrophoblast development was associated with deacetylation of multiple core histone residues. Chromatin immunoprecipitation sequencing revealed chromosomal regions that exhibit dynamic alterations in histone H3 acetylation during differentiation. These include regions containing genes classically associated with cytotrophoblast differentiation (TEAD4, TP63, OVOL1, CGB), as well as near genes with novel regulatory roles in trophoblast development and function, such as LHX4 and SYDE1. Prevention of histone deacetylation using both pharmacological and genetic approaches inhibited trophoblast fusion, supporting a critical role of this process for trophoblast differentiation. Finally, we identified the histone deacetylases (HDACs) HDAC1 and HDAC2 as the critical mediators driving cytotrophoblast differentiation. Collectively, these findings provide novel insights into the epigenetic mechanisms underlying trophoblast fusion during human placental development

Regulation of c-Raf stability through the CTLH complex

c-Raf is a central component of the extracellular signal-regulated kinase (ERK) pathway which is implicated in the development of many cancer types. RanBPM (Ran-Binding Protein M) was previously shown to inhibit c-Raf expression, but how this is achieved remains unclear. RanBPM is part of a recently identified E3 ubiquitin ligase complex, the CTLH (C-terminal to LisH) complex. Here, we show that the CTLH complex regulates c-Raf expression through a control of its degradation. Several domains of RanBPM were found necessary to regulate c-Raf levels, but only the C-terminal CRA (CT11-RanBPM) domain showed direct interaction with c-Raf. c-Raf ubiquitination and degradation is promoted by the CTLH complex. Furthermore, A-Raf and B-Raf protein levels are also regulated by the CTLH complex, indicating a common regulation of Raf family members. Finally, depletion of CTLH subunits RMND5A (required for meiotic nuclear division 5A) and RanBPM resulted in enhanced proliferation and loss of RanBPM promoted tumour growth in a mouse model. This study uncovers a new mode of control of c-Raf expression through regulation of its degradation by the CTLH complex. These findings also uncover a novel target of the CTLH complex, and suggest that the CTLH complex has activities that suppress cell transformation and tumour formation

Atrx Deletion in Neurons Leads to Sexually Dimorphic Dysregulation of miR-137 and Spatial Learning and Memory Deficits.

ATRX gene mutations have been identified in syndromic and non-syndromic intellectual disabilities in humans. ATRX is known to maintain genomic stability in neuroprogenitor cells, but its function in differentiated neurons and memory processes remains largely unresolved. Here, we show that the deletion of neuronal Atrx in mice leads to distinct hippocampal structural defects, fewer presynaptic vesicles, and an enlarged postsynaptic area at CA1 apical dendrite-axon junctions. We identify male-specific impairments in long-term contextual memory and in synaptic gene expression, linked to altered miR-137 levels. We show that ATRX directly binds to the miR-137 locus and that the enrichment of the suppressive histone mark H3K27me3 is significantly reduced upon the loss of ATRX. We conclude that the ablation of ATRX in excitatory forebrain neurons leads to sexually dimorphic effects on miR-137 expression and on spatial memory, identifying a potential therapeutic target for neurological defects caused by ATRX dysfunction

The population genomic structure of green turtles (<i>Chelonia mydas</i>) suggests a warm-water corridor for tropical marine fauna between the Atlantic and Indian oceans during the last interglacial

The occasional westward transport of warm water of the Agulhas Current, “Agulhas leakage”, around southern Africa has been suggested to facilitate tropical marine connectivity between the Atlantic and Indian oceans, but the “Agulhas leakage” hypothesis does not explain the signatures of eastward gene flow observed in many tropical marine fauna. We investigated an alternative hypothesis: the establishment of a warm-water corridor during comparatively warm interglacial periods. The “warm-water corridor” hypothesis was investigated by studying the population genomic structure of Atlantic and Southwest Indian Ocean green turtles (N = 27) using 12,035 genome-wide single nucleotide polymorphisms (SNPs) obtained via ddRAD sequencing. Model-based and multivariate clustering suggested a hierarchical population structure with two main Atlantic and Southwest Indian Ocean clusters, and a Caribbean and East Atlantic sub-cluster nested within the Atlantic cluster. Coalescent-based model selection supported a model where Southwest Indian Ocean and Caribbean populations diverged from the East Atlantic population during the transition from the last interglacial period (130–115 thousand years ago; kya) to the last glacial period (115–90 kya). The onset of the last glaciation appeared to isolate Atlantic and Southwest Indian Ocean green turtles into three refugia, which subsequently came into secondary contact in the Caribbean and Southwest Indian Ocean when global temperatures increased after the Last Glacial Maximum. Our findings support the establishment of a warm-water corridor facilitating tropical marine connectivity between the Atlantic and Southwest Indian Ocean during warm interglacials