Impact of bronchial epithelium on dendritic cell migration and function: modulation by the bacterial motif KpOmpA

Mucosal immune response depends on the surveillance network established by dendritic cells (DC), APC localized within the epithelium. Bronchial epithelial cells (BEC) play a pivotal role both in the host defense and in the pathogenesis of inflammatory airway disorders. We previously showed that the outer membrane protein A from Klebsiella pneumoniae (KpOmpA), a pathogen-associated molecular pattern (PAMP) derived from Klebsiella pneumoniae, activates BEC. In this study, we evaluated the consequences of this activation on DC traffic and functions. KpOmpA significantly increased the production of CCL2, CCL5, CXCL10, and CCL20 by BEC. Stimulation of BEC increased their chemotactic activity for monocyte-derived DC (MDDC) precursors, through CCL5 and CXCL10 secretion. BEC/MDDC precursor coculture leads to an ICAM-1-dependent accelerated differentiation and enhanced maturation of MDDC. BEC/DC interactions did not affect the capacity of DC to induce T cell proliferation. However, DC preincubated with BEC increased significantly the IL-10 production by autologous T cells. Basolateral and intraepithelial DC differently enhance IL-4 and/or IL-10 synthesis according to the condition of stimulation. In vivo, intranasal injections of KpOmpA into BALB/c mice induced the recruitment of CD11c(+) and I-A(d+) myeloid DC associated with bronchial epithelium activation as evidenced by CCL20 expression. These data show that KpOmpA-exposed BEC participate in the homeostasis of myeloid DC network, and regulate the induction of local immune response.     

Bottlenecks in domestic animal populations can facilitate the emergence of Trypanosoma cruzi,the aetiological agent of Chagas disease

Faeces-mediated transmission of Trypanosoma cruzi (the aetiological agent of Chagas disease) by triatomine insects is extremely inefficient. Still, the parasite emerges frequently, and has infected millions of people and domestic animals. We synthesize here the results of field and laboratory studies of T. cruzi transmission conducted in and around Arequipa, Peru. We document the repeated occurrence of large colonies of triatomine bugs (more than 1000) with very high infection prevalence (more than 85%). By inoculating guinea pigs, an important reservoir of T. cruzi in Peru, and feeding triatomine bugs on them weekly, we demonstrate that, while most animals quickly control parasitaemia, a subset of animals remains highly infectious to vectors for many months. However, we argue that the presence of these persistently infectious hosts is insufficient to explain the observed prevalence of T. cruzi in vector colonies. We posit that seasonal rains, leading to a fluctuation in the price of guinea pig food (alfalfa), leading to annual guinea pig roasts, leading to a concentration of vectors on a small subpopulation of animals maintained for reproduction, can propel T. cruzi through vector colonies and create a considerable force of infection for a pathogen whose transmission might otherwise fizzle out.     

Changes in the concentrations of glucose, non-esterified fatty acids, urea, insulin, cortisol and some mineral elements in the plasma of the primiparous sow before, during and after induced parturition.

The concentrations of selected metabolites, minerals and hormones relative to parturition were studied in 12 primiparous sows. Blood sampling was performed on day -5, 0 and +5 relative to the farrowing day. On the day of parturition (d 0), samples were taken every hour from 07.00 to 24.00 hours. All sows had an indwelling catheter in the jugular vein, and the evolution of glucose, insulin, urea, non-esterified fatty acids (UEFA), calcium (Ca), phosphorus (P), magnesium (Mg) and cortisol were studied. The concentrations of NEFA, cortisol and P were significantly higher at d 0 than at d -5 or d +5, whereas the Mg level was lower. During the expulsion of foetuses, NEFA and cortisol levels increased (+18 and +30%, respectively), and they decreased immediately after the birth of the last piglet, to reach the initial levels observed before farrowing (around 700 microEq.L-1 and 110 ng.mL-1, respectively). Glucose and insulin levels remained unchanged during the expulsion of the piglets (105 ng.dL-1 and 5 microIU.mL-1, respectively), but they both increased immediately after the birth of the last animal. During the expulsion of the foetuses, the Ca concentration remained unchanged (93 mg.L-1), whereas the P level increased (+9%) and the Mg concentration decreased (-7.4%). These data suggested that parturition induces large variations in the concentrations of plasma metabolites that may affect its normal process.     

Virtual screening on an α‐helix to β‐strand switchable region of the FGFR2 extracellular domain revealed positive and negative modulators

The secondary structure of some protein segments may vary between α‐helix and β‐strand. To predict these switchable segments, we have developed an algorithm, Switch‐P, based solely on the protein sequence. This algorithm was used on the extracellular parts of FGF receptors. For FGFR2, it predicted that β4 and β5 strands of the third Ig‐like domain were highly switchable. These two strands possess a high number of somatic mutations associated with cancer. Analysis of PDB structures of FGF receptors confirmed the switchability prediction for β5. We thus evaluated if compound‐driven α‐helix/β‐strand switching of β5 could modulate FGFR2 signaling. We performed the virtual screening of a library containing 1.4 million of chemical compounds with two models of the third Ig‐like domain of FGFR2 showing different secondary structures for β5, and we selected 32 compounds. Experimental testing using proliferation assays with FGF7‐stimulated SNU‐16 cells and a FGFR2‐dependent Erk1/2 phosphorylation assay with FGFR2‐transfected L6 cells, revealed activators and inhibitors of FGFR2. Our method for the identification of switchable proteinic regions, associated with our virtual screening approach, provides an opportunity to discover new generation of drugs with under‐explored mechanism of action. Proteins 2014; 82:2982–2997. © 2014 Wiley Periodicals, Inc.     

Mid-Cretaceous Burmese amber pelecinid wasps (Hymenoptera,Pelecinidae) support the hypothesis of an Asian origin of the family

A new species of pelecinid wasp, Eopelecinus marechali sp. nov., is described and figured from mid-Cretaceous Burmese amber based on a single well-preserved female specimen. Contrary to Eopelecinus inopinatus Jouault et al., 2020a, unique other Eopelecinus known from this deposit, the new species is based on a complete female specimen. This discovery confirms that the Pelecinidae were highly diverse during the Cretaceous and highlights the underestimated diversity of the genus Eopelecinus in Burmese amber biota. Eopelecinus marechali sp. nov. differs from all other Eopelecinus species by its unique metasomal ratio. A summary on the fossil pelecinid species with distributions and ages is provided. Based on the particular geological history of the West Burmese Terrane and the fossil record of the family, the hypothesis of an Asian origin of the family is discussed. The records of Eopelecinus in both Laurasia and Burmese amber biota, during the mid-Cretaceous, suggest that possible transfers of fauna have taken place between these two geological blocks.     

A Scalable Computational Framework for Establishing Long-Term Behavior of Stochastic Reaction Networks

Reaction networks are systems in which the populations of a finite number of species evolve through predefined interactions. Such networks are found as modeling tools in many biological disciplines such as biochemistry, ecology, epidemiology, immunology, systems biology and synthetic biology. It is now well-established that, for small population sizes, stochastic models for biochemical reaction networks are necessary to capture randomness in the interactions. The tools for analyzing such models, however, still lag far behind their deterministic counterparts. In this paper, we bridge this gap by developing a constructive framework for examining the long-term behavior and stability properties of the reaction dynamics in a stochastic setting. In particular, we address the problems of determining ergodicity of the reaction dynamics, which is analogous to having a globally attracting fixed point for deterministic dynamics. We also examine when the statistical moments of the underlying process remain bounded with time and when they converge to their steady state values. The framework we develop relies on a blend of ideas from probability theory, linear algebra and optimization theory. We demonstrate that the stability properties of a wide class of biological networks can be assessed from our sufficient theoretical conditions that can be recast as efficient and scalable linear programs, well-known for their tractability. It is notably shown that the computational complexity is often linear in the number of species. We illustrate the validity, the efficiency and the wide applicability of our results on several reaction networks arising in biochemistry, systems biology, epidemiology and ecology. The biological implications of the results as well as an example of a non-ergodic biological network are also discussed.