Cytogenetic mapping of a major locus for resistance to Fusarium head blight and crown rot of wheat on <Emphasis Type="Italic">Thinopyrum elongatum</Emphasis> 7EL and its pyramiding with valuable genes from a <Emphasis Type="Italic">Th. ponticum</Emphasis> homoeologous arm onto bread wheat 7DL

Key message

A major locus for resistance to different Fusarium diseases was mapped to the most distal end of Th. elongatum 7EL and pyramided with Th. ponticum beneficial genes onto wheat 7DL.

Abstract

Perennial Triticeae species of the Thinopyrum genus are among the richest sources of valuable genes/QTL for wheat improvement. One notable and yet unexploited attribute is the exceptionally effective resistance to a major wheat disease worldwide, Fusarium head blight, associated with the long arm of Thinopyrum elongatum chromosome 7E (7EL). We targeted the transfer of the temporarily designated Fhb-7EL locus into bread wheat, pyramiding it with a Th. ponticum 7el₁L segment stably inserted into the 7DL arm of wheat line T4. Desirable genes/QTL mapped along the T4 7el₁L segment determine resistance to wheat rusts (Lr19, Sr25) and enhancement of yield-related traits. Mapping of the Fhb-7EL QTL, prerequisite for successful pyramiding, was established here on the basis of a bioassay with Fusarium graminearum of different 7EL-7el₁L bread wheat recombinant lines. These were obtained without resorting to any genetic pairing promotion, but relying on the close 7EL-7el₁L homoeology, resulting in 20% pairing frequency between the two arms. Fhb-7EL resided in the telomeric portion and resistant recombinants could be isolated with useful combinations of more proximally located 7el₁L genes/QTL. The transferred Fhb-7EL locus was shown to reduce disease severity and fungal biomass in grains of infected recombinants by over 95%. The same Fhb-7EL was, for the first time, proved to be effective also against F. culmorum and F. pseudograminearum, predominant agents of crown rot. Prebreeding lines possessing a suitable 7EL-7el₁L gene/QTL assembly showed very promising yield performance in preliminary field tests.

     

Paclitaxel binds and activates C5aR1: A new potential therapeutic target for the prevention of chemotherapy-induced peripheral neuropathy and hypersensitivity reactions

Chemotherapy-induced peripheral neuropathy (CIPN) and hypersensitivity reactions (HSRs) are among the most frequent and impairing side effects of the antineoplastic agent paclitaxel. Here, we demonstrated that paclitaxel can bind and activate complement component 5a receptor 1 (C5aR1) and that this binding is crucial in the etiology of paclitaxel-induced CIPN and anaphylaxis. Starting from our previous data demonstrating the role of interleukin (IL)-8 in paclitaxel-induced neuronal toxicity, we searched for proteins that activate IL-8 expression and, by using the Exscalate platform for molecular docking simulations, we predicted the high affinity of C5aR1 with paclitaxel. By in vitro studies, we confirmed the specific and competitive nature of the C5aR1-paclitaxel binding and found that it triggers intracellularly the NFkB/P38 pathway and c-Fos. In F11 neuronal cells and rat dorsal root ganglia, C5aR1 inhibition protected from paclitaxel-induced neuropathological effects, while in paclitaxel-treated mice, the absence (knock-out mice) or the inhibition of C5aR1 significantly ameliorated CIPN symptoms—in terms of cold and mechanical allodynia—and reduced the chronic pathological state in the paw. Finally, we found that C5aR1 inhibition can counteract paclitaxel-induced anaphylactic cytokine release in macrophages in vitro, as well as the onset of HSRs in mice. Altogether these data identified C5aR1 as a key mediator and a new potential pharmacological target for the prevention and treatment of CIPN and HSRs induced by paclitaxel.Subject terms: Pathogenesis, Immunopathogenesis     

Predictive functional ANOVA models for longitudinal analysis of mandibular shape changes

In this paper, we introduce a Bayesian statistical model for the analysis of functional data observed at several time points. Examples of such data include the Michigan growth study where we wish to characterize the shape changes of human mandible profiles. The form of the mandible is often used by clinicians as an aid in predicting the mandibular growth. However, whereas many studies have demonstrated the changes in size that may occur during the period of pubertal growth spurt, shape changes have been less well investigated. Considering a group of subjects presenting normal occlusion, in this paper we thus describe a Bayesian functional ANOVA model that provides information about where and when the shape changes of the mandible occur during different stages of development. The model is developed by defining the notion of predictive process models for Gaussian process (GP) distributions used as priors over the random functional effects. We show that the predictive approach is computationally appealing and that it is useful to analyze multivariate functional data with unequally spaced observations that differ among subjects and times. Graphical posterior summaries show that our model is able to provide a biological interpretation of the morphometric findings and that they comprehensively describe the shape changes of the human mandible profiles. Compared with classical cephalometric analysis, this paper represents a significant methodological advance for the study of mandibular shape changes in two dimensions.     

Striae albae: a morphological study on the human skin

Specimens of abdomen skin, comprising alternate areas of striae albae and healthy skin, were removed during surgical lipectomy from multiparous and obese women between the ages of 24 and 53 years. A flattening and thinning of the striae albae surface and the almost complete disappearance of dermal papillae was observed in paraffin and thin sections. The papillary dermis was found to be almost completely replaced by straight bundles of collagen fibres running parallel to the skin surface. Immunofluorescence data revealed in these bundles high positivity for type I collagen. The underlying reticular dermis was also found to contain large densely packed bundles of collagen fibres running parallel to the skin surface. Both papillary and reticular dermis collagen fibres were mainly arranged orthogonally to the main axis of the stria. Furthermore, the density of the collagen fibre bundles and the diameter of the collagen fibrils was found to be greater than that of the clinically healthy skin. A larger number of elastic fibres, which presented an abnormal ultrastructural appearance, were visible in pathological papillary and reticular dermis.     

Tag loss is a minor limiting factor in sea turtle tagging programs relying on distant tag returns: the case of Mediterranean loggerhead sea turtles

As in many other species, tagging has been routinely conducted for decades in over a hundred sea turtle capture-mark-recapture (CMR) programs worldwide. Tag loss is a key limiting factor because it violates the main assumption in CMR models; however, very few estimates of tag loss exist, and we provide here a review. No published estimations of tag loss are available for the Mediterranean, in spite of intensive tagging since the 1980s. This study aims to provide an estimation of tag loss in loggerhead turtles tagged in the Mediterranean. We modeled 64 tag returns out of ca. 2200 loggerhead turtles tagged at Mediterranean foraging grounds, with mark-recapture intervals up to 11.5 years, in order to estimate a daily tag loss probability of the most used tag applied to the most common turtle species in the region. Five models were evaluated through maximum likelihood estimation. The model with the best fit described a tag loss initially high and then decreasing to a lower asymptote, which is probably due to some defective tag applications. The resulting tag loss (0.15 in the first year and 0.31 after 5 years) was comparable or even lower than those from other areas and/or species and predictions indicate that double tagging can make a turtle identifiable for a long period. Hence, in our tagging program and probably in similar ones as well, tag loss appears to be the less important of the factors affecting tag returns, and efforts in other directions are more likely to improve CMR results.     

Peritoneal dialysis fluid activates calcium signaling and apoptosis in mesothelial cells

A larger diffusion of peritoneal dialysis (PD) is limited by the progressive deterioration of the dialysis membrane structure and function, characterized in vitro and in vivo by mesothelial cell loss and closely related to the use of bioincompatible dialysis solutions. The apoptosis rate of rat and human mesothelial cells incubated in commercial PD fluid (PDF, 4.25 g/dL dextrose) became significant as early as 1 h after PDF addition and reached a plateau at 4–5 h. This pattern was unchanged after exposure to 1.5 g/dL dextrose PDF or freshly prepared PDF, indicating that effects were independent on the dextrose strength and manufacturing procedures but strictly dependent on PDF composition. Molecular studies revealed that PDF exposure inactivated the physiological volume recovery from hypertonic shrinkage, accompanied by an abnormal Ca²⁺ signaling: a progressive intracellular Ca²⁺ ([Ca²⁺]_i) rise resulting from an increased Ca²⁺ entry. PDF also affected cytoskeleton integrity: early dissolution of actin filaments occurred well before the appearance of typical apoptosis features. Lastly, the PDF dependent apoptosis was almost completely prevented by the contemporary Ca²⁺ concentration decrease and K⁺ addition. This study suggests that the PDF dependent apoptosis arises from the extreme volume perturbations in mesothelial cells, turned out unable to regulate their volume back once exposed to a hyperosmolal medium containing high Ca²⁺ levels in the absence of K⁺, such PDF.     

The lethal moiety of the surface slime glycolipoprotein ofPseudomonas aeruginosa

Phenol treatment of the glycolipoprotein fromPseudomonas aeruginosa, followed by gel filtration and anion-exchange chromatography, produced a glycolipid fragment free of protein. A second, lipid-rich fragment was obtained as a precipitate of dilute acetic-acid hydrolysis of the glycolipoprotein. After solubilization, the lipid-rich fragment was processed on Sephadex G-200. Both lipid-containing fragments were immunologically homogeneous in Ouchterlony plates against rabbit antiserum to crude glycolipoprotein. The precipitin bands indicated that polysaccharide residues conferred the antigenic specificity. General chemical analyses were made on each fragment. All lipid-containing fragments were lethal, to varying degrees, on injection in mice. Proteinase K digestion of the glycolipoprotein did not reduce its lethality. All lipid-containg fragments stimulated varying levels of antibody capable of passively protecting mice against lethal challenge with viablePseudomonas aeruginosa. The contribution of the carbohydrate moiety to the expression of lethality is discussed.