Fgf19 expression patterns in the developing chick inner ear

The inner ear is a complex sensorial structure with hearing and balance functions. A key aim of developmental biology is to understand the molecular and cellular mechanisms involved in the induction, patterning and innervation of the vertebrate inner ear. These developmental events could be mediated by the expression of regulating genes, such as the members of the family of Fibroblast Growth Factors (Fgfs). This work reports the detailed spatial and temporal patterns of Fgf19 expression in the developing inner ear from otic cup (stage 14) to 8 embryonic days (stage 34). In the earliest stages, Fgf19 and Fgf8 expressions determine two subdomains within the Fgf10-positive proneural-sensory territory. We show that, from the earliest stages, the Fgf19 expression was detected in the acoustic-vestibular ganglion and the macula utriculi. The Fgf19 gene was also strongly, but transiently, expressed in the macula lagena, whereas the macula neglecta never expressed this gene in the period analysed. The Fgf19 expression was also clearly observed in some borders of various sensory elements. These results could be useful from further investigations into the role of FGF19 in otic patterning.     

Transfer of glyphosate resistance: evidence of hybridization in Conyza (Asteraceae)

Transfer of herbicide resistance genes between crops and weeds is relatively well documented; however, far less information exists for weed-to-weed interactions. The hybridization between the weedy diploids Conyza canadensis (2n = 18) and C. ramosissima (2n = 18) was investigated by monitoring transmission of the allele conferring resistance to N-phosphonomethyl glycine (glyphosate). In a multivariate quantitative trait analysis, we described the phylogenic relationship of the plants, whereas we tested seed viability to assess potential postzygotic reproductive barriers (PZRB) thus affecting the potential establishment of hybrid populations in the wild. When inflorescences were allowed to interact freely, approximately 3% of C. ramosissima or C. canadensis ova were fertilized by pollen of the opposing species and produced viable seeds; >95% of the ova were fertilized under no-pollen competition conditions (emasculation). The interspecific Conyza hybrid ( ) demonstrated an intermediate phenotype between the parents but superior resistance to glyphosate compared to the resistant C. canadensis parent. Inheritance of glyphosate resistance in the selfed ( ) followed the partially dominant nuclear, single-gene model; backcrosses confirmed successful introgression of the resistance allele to either parent. Negligible PZRB were observed in the hybrid progenies, confirming fertility of the C. canadensis × C. ramosissima nothotaxa. The implications of introgressive hybridization for herbicide resistance management and taxonomy of Conyza are discussed.     

Enhancing Sensorimotor Activity by Controlling Virtual Objects with Gaze

This fMRI work studies brain activity of healthy volunteers who manipulated a virtual object in the context of a digital game by applying two different control methods: using their right hand or using their gaze. The results show extended activations in sensorimotor areas, not only when participants played in the traditional way (using their hand) but also when they used their gaze to control the virtual object. Furthermore, with the exception of the primary motor cortex, regional motor activity was similar regardless of what the effector was: the arm or the eye. These results have a potential application in the field of the neurorehabilitation as a new approach to generate activation of the sensorimotor system to support the recovery of the motor functions.     

Androgen receptor acetylation sites differentially regulate gene control

Androgen receptor (AR) function is modulated by post-translational modifications such as acetylation, ubiquitylation, sumoylation, and phosphorylation. Concerning acetylation, three lysines residues located in a consensus KxKK motif of the AR hinge domain have been identified. For a better evaluation of the role of this modification, the activity of AR modified at different acetylation sites was determined by comparing the effects on natural and synthetic promoters. We found that mutation of AR acetylation sites affected both potency and efficacy of androgen-dependent response. Remarkably, elimination of all three acetylation sites was still compatible with strong AR activity on the PSA and MMTV promoters, but not on the Pem promoter. This differential effect was seen at various wild-type (wt) to mutant AR receptor ratios and at changing hormone concentrations. Subcellular localization studies showed that both mutated and wt AR efficiently translocated into the cell nucleus. Plasmid immunoprecipitation revealed comparable binding of both receptor forms to the Pem promoter. The differential effects observed for the Pem promoter were partially due to an androgen response element (ARE) named ARE-1 which was only poorly stimulated by the AR acetylation site mutant. Finally, AR mutants impaired in their N/C interaction elicited intact stimulation of the Pem promoter, suggesting that AR acetylation was not influenced by this inter-domain communication. The promoter-selective effects seen for the AR acetylation site mutants strongly suggest this post-translational modification to be important in the fine-tuning of the effects of androgens on different target genes.     

A Protein-Conjugate Approach to Develop a Monoclonal Antibody-Based Antigen Detection Test for the Diagnosis of Human Brucellosis

Human brucellosis is most commonly diagnosed by serology based on agglutination of fixed Brucella abortus as antigen. Nucleic acid amplification techniques have not proven capable of reproducibly and sensitively demonstrating the presence of Brucella DNA in clinical specimens. We sought to optimize a monoclonal antibody-based assay to detect Brucella melitensis lipopolysaccharide in blood by conjugating B. melitensis LPS to keyhole limpet hemocyanin, an immunogenic protein carrier to maximize IgG affinity of monoclonal antibodies. A panel of specific of monoclonal antibodies was obtained that recognized both B. melitensis and B. abortus lipopolysaccharide epitopes. An antigen capture assay was developed that detected B. melitensis in the blood of experimentally infected mice and, in a pilot study, in naturally infected Peruvian subjects. As a proof of principle, a majority (7/10) of the patients with positive blood cultures had B. melitensis lipopolysaccharide detected in the initial blood specimen obtained. One of 10 patients with relapsed brucellosis and negative blood culture had a positive serum antigen test. No seronegative/blood culture negative patients had a positive serum antigen test. Analysis of the pair of monoclonal antibodies (2D1, 2E8) used in the capture ELISA for potential cross-reactivity in the detection of lipopolysaccharides of E. coli O157:H7 and Yersinia enterocolitica O9 showed specificity for Brucella lipopolysaccharide. This new approach to develop antigen-detection monoclonal antibodies against a T cell-independent polysaccharide antigen based on immunogenic protein conjugation may lead to the production of improved rapid point-of-care-deployable assays for the diagnosis of brucellosis and other infectious diseases.     

Influence of Novel Gallium Complexes on the Homeostasis of Some Biochemical and Hematological Parameters in Rats

Chronic overexposure to cobalt (Co) may result in neurotoxic effects, but the mechanism of Co-induced neurotoxicity is not yet well established. Our study was conducted to determine whether Co is associated to the induction of central nervous system damage in pregnant rats and their progeny. Twelve pregnant female rats were randomly divided into 2 groups: group I served as controls and group II received Co (350 mg/L, orally). Treatments started from the 14th day of pregnancy until day 14 after delivery. Co concentration in plasma was higher in the treated groups than in the controls. Exposure to Co also increased the levels of MDA, PCO, H₂O₂, and AOPP, while Na⁺K⁺-ATPase and Mg²⁺-ATPase, AChE, and BuChE activities decreased in the cerebrum and cerebellum of suckling pups. A smear without ladder formation on agarose gel was also shown in the cerebrum and cerebellum, indicating random DNA degradation. A reduction in GPx, SOD, CAT, GSH, NPSH, and vitamin C values was observed. The changes were confirmed by histological results. In conclusion, these data showed that the exposure of pregnant and lactating rats to Co resulted in the development of oxidative stress and the impairment of defense systems in the cerebrum and cerebellum of their suckling pups.