The evolution of brood parasitism: the role of facultative parasitism

The hypothesis that facultative brood parasitism may serve asan intermediate step in the evolutionary transition from purelyparental reproduction to obligate parasitism was investigated.The population dynamics of a host-parasite complex were computer-simulatedin a model that incorporated different intensities of parasitismand host defense and considered a simplified semelparous birdspecies living in a homogeneous habitat The individuals usetwo different breeding strategies: provide parental care orparasitize the nest of those providing parental care. Underobligate parasitism, the parasites appeared unsuccessful, drovethe host population to extinction, or coexisted with the hostin stable or oscillating proportions. The behavior of the systemdepended on both the effectiveness of the parasite and the defenseof the host. Under facultative parasitism (making the best ofa bad job), the parasites reduced host numbers but did not reducethe population size below the number of breeding sites. Thus,facultative parasitism provides a better opportunity for thedevelopment of defense in the host. The population of a hostthat shows a certain level of defense can be more successfullyinvaded by obligate parasites so that stable coexistence ofhosts and parasites is possible.     

Gap junction structures: Analysis of the x-ray diffraction data

Models for the spatial distribution of protein, lipid and water in gap junction structures have been constructed from the results of the analysis of X-ray diffraction data described here and the electron microscope and chemical data presented in the preceding paper (Caspar, D. L. D., D. A. Goodenough, L. Makowski, and W.C. Phillips. 1977. 74:605-628). The continuous intensity distribution on the meridian of the X-ray diffraction pattern was measured, and corrected for the effects of the partially ordered stacking and partial orientation of the junctions in the X-ray specimens. The electron density distribution in the direction perpendicular to the plane of the junction was calculated from the meridional intensity data. Determination of the interference function for the stacking of the junctions improved the accuracy of the electron density profile. The pair-correlation function, which provides information about the packing of junctions in the specimen, was calculated from the interference function. The intensities of the hexagonal lattice reflections on the equator of the X-ray pattern were used in coordination with the electron microscope data to calculate to the two-dimensional electron density projection onto the plane of the membrane. Differences in the structure of the connexons as seen in the meridional profile and equatorial projections were shown to be correlated to changes in lattice constant. The parts of the junction structure which are variable have been distinguished from the invariant parts by comparison of the X-ray data from different specimens. The combination of these results with electron microscope and chemical data provides low resolution three- dimensional representations of the structures of gap junctions.     

Innate immunity orchestrates the mobilization and homing of hematopoietic stem/progenitor cells by engaging purinergic signaling—an update

Purinergic Signalling - Bone marrow (BM) as an active hematopoietic organ is highly sensitive to changes in body microenvironments and responds to external physical stimuli from the surrounding...     

Covid‐19.bioreproducibility.org: A web resource for SARS‐CoV‐2‐related structural models

The COVID‐19 pandemic has triggered numerous scientific activities aimed at understanding the SARS‐CoV‐2 virus and ultimately developing treatments. Structural biologists have already determined hundreds of experimental X‐ray, cryo‐EM, and NMR structures of proteins and nucleic acids related to this coronavirus, and this number is still growing. To help biomedical researchers, who may not necessarily be experts in structural biology, navigate through the flood of structural models, we have created an online resource, covid19.bioreproducibility.org, that aggregates expert‐verified information about SARS‐CoV‐2‐related macromolecular models. In this article, we describe this web resource along with the suite of tools and methodologies used for assessing the structures presented therein.     

Parkin-independent mitophagy via Drp1-mediated outer membrane severing and inner membrane ubiquitination

Here, we report that acute reduction in mitochondrial translation fidelity (MTF) causes ubiquitination of the inner mitochondrial membrane (IMM) proteins, including TRAP1 and CPOX, which occurs selectively in mitochondria with a severed outer mitochondrial membrane (OMM). Ubiquitinated IMM recruits the autophagy machinery. Inhibiting autophagy leads to increased accumulation of mitochondria with severed OMM and ubiquitinated IMM. This process occurs downstream of the accumulation of cytochrome c/CPOX in a subset of mitochondria heterogeneously distributed throughout the cell (“mosaic distribution”). Formation of mosaic mitochondria, OMM severing, and IMM ubiquitination require active mitochondrial translation and mitochondrial fission, but not the proapoptotic proteins Bax and Bak. In contrast, in Parkin-overexpressing cells, MTF reduction does not lead to the severing of the OMM or IMM ubiquitination, but it does induce Drp1-independent ubiquitination of the OMM. Furthermore, high–cytochrome c/CPOX mitochondria are preferentially targeted by Parkin, indicating that in the context of reduced MTF, they are mitophagy intermediates regardless of Parkin expression. In sum, Parkin-deficient cells adapt to mitochondrial proteotoxicity through a Drp1-mediated mechanism that involves the severing of the OMM and autophagy targeting ubiquitinated IMM proteins.     

Transforming growth factor-β1 signalling triggers vascular endothelial growth factor resistance and monocyte dysfunction in type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) leads to monocyte dysfunction associated with atherogenesis and defective arteriogenesis. Transforming growth factor (TGF)-β1, placenta growth factor (PlGF)-1 and vascular endothelial growth factor (VEGF)A play important roles in atherogenesis and arteriogenesis. VEGF-receptor (VEGFR)-mediated monocyte migration is inhibited in T2DM (VEGFA resistance), while TGF-β1-induced monocyte migration is fully functional. Therefore, we hypothesize that TGF-β antagonises the VEGFA responses in human monocytes. We demonstrate that monocytes from T2DM patients have an increased migratory response towards low concentrations of TGF-β1, while PlGF-1/VEGFA responses are mitigated. Mechanistically, this is due to increased expression of type II TGF-β receptor in monocytes under high-glucose conditions and increased expression of soluble (s)VEGFR1, which is known to interfere with VEGFA signalling. VEGFA resistance in monocytes from T2DM patients can be rescued by either experimental down-regulation of TGF-β receptor expression in vitro or by functional blocking of TGF-β signalling using either a TGF-β receptor kinase inhibitor or a TGF-β neutralizing antibody. Our data demonstrate that both T2DM and high-glucose potentiate the TGF-β pathway. TGF-β signalling impairs VEGFR-mediated responses in T2DM monocytes and in this way contributes to mononuclear cell dysfunction, provide novel insights into T2DM vascular dysfunction.     

Solid phase synthesis of peptide hydroxamic acids on poly(ethylene glycol)‐based support

A novel resin designed for solid‐phase synthesis of peptide hydroxamic acids (PHA) combining the trityl linker with poly(ethylene glycol)‐based support, ChemMatrix® type, is described. The synthesis of PHA can be performed according to a standard protocol, providing products in excellent purity and reasonable yields. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.     

2-Methylwyosine,a Nucleoside With Restricted Anti Conformation in the East Region Enforced by Nucleobase Moiety Modification: Synthesis and Conformational Analysis by NMR and Molecular Dynamics

GRAPHICAL ABSTRACT

We synthesized a new 2-methyl derivative of wyosine using a multistep procedure starting from guanosine. We examined different synthetic paths and optimized the conditions for each step. Based on MD calculations and analysis of the ³ J _HH and J _C1′H1′ of the ribose moiety, we discovered that the sugar part adopted conformation specific for the East region rarely occurring in solution. This unusual conformational preference is probably due to steric repulsions between the methyl group at position 2 and the 5′-CH₂OH group. We observed that N-glycosidic bond stability weakened 14-fold upon the introduction of the methyl group in position 2 compared with wyosine.     

Comparison of Statistical Models for Analyzing Wheat Yield Time Series

The world''s population is predicted to exceed nine billion by 2050 and there is increasing concern about the capability of agriculture to feed such a large population. Foresight studies on food security are frequently based on crop yield trends estimated from yield time series provided by national and regional statistical agencies. Various types of statistical models have been proposed for the analysis of yield time series, but the predictive performances of these models have not yet been evaluated in detail. In this study, we present eight statistical models for analyzing yield time series and compare their ability to predict wheat yield at the national and regional scales, using data provided by the Food and Agriculture Organization of the United Nations and by the French Ministry of Agriculture. The Holt-Winters and dynamic linear models performed equally well, giving the most accurate predictions of wheat yield. However, dynamic linear models have two advantages over Holt-Winters models: they can be used to reconstruct past yield trends retrospectively and to analyze uncertainty. The results obtained with dynamic linear models indicated a stagnation of wheat yields in many countries, but the estimated rate of increase of wheat yield remained above 0.06 t ha⁻¹ year⁻¹ in several countries in Europe, Asia, Africa and America, and the estimated values were highly uncertain for several major wheat producing countries. The rate of yield increase differed considerably between French regions, suggesting that efforts to identify the main causes of yield stagnation should focus on a subnational scale.