Studies of esterase 6 in Drosophila melanogaster. XVIII. Biochemical differences between the slow and fast allozymes

Most natural populations of Drosophila melanogaster are polymorphic for two major electrophoretic variants at the esterase-6 locus. The frequency of the EST 6F allozyme is greatest in populations in warmer latitudes, whereas the EST 6S allozyme is predominant in colder latitudes. Latitudinal clines in electromorph frequencies are found on three continents. Purified preparations of the allozymes have been characterized for their pH optimum, substrate specificity, organophosphate inhibition, alcohol activation, thermal stability, and kinetic parameters. These and previous analyses of the EST 6 allozymes reveal that the two variants have differences in their physical and kinetic properties that may provide a basis for the selective maintenance of the polymorphisms and an explanation of the clinal variation observed in natural populations.      

Immunological Characterization of Whole Tumour Lysate-Loaded Dendritic Cells for Cancer Immunotherapy

IntroductionDendritic cells play a key role as initiators of T-cell responses, and even if tumour antigen-loaded dendritic cells can induce anti-tumour responses, their efficacy has been questioned, suggesting a need to enhance immunization strategies.ResultsResults showed that antigen-loaded dendritic cells are characterized by a phenotypically semi-mature/mature profile and by the upregulation of genes involved in antigen presentation and T-cell priming. Activated dendritic cells stimulated T-cell proliferation and induced the production of high concentrations of IL-12p70 and IFN-γ but only low levels of IL-10, indicating their ability to elicit a T_H1-immune response. Furthermore, administration of Antigen loaded-Dendritic Cells in MMTV-Ras mice evoked a strong anti-tumour response in vivo as demonstrated by a general activation of immunocompetent cells and the release of T_H1 cytokines.ConclusionData herein could be useful in the design of antitumoral DC-based therapies, showing a specific activation of immune system against breast cancer.     

Lymphotoxin: from the physiology to the regeneration of the thymic function

The members of the Tumor Necrosis Factor (TNF) superfamily, the ligand lymphotoxin α1β2 (LTα1β2) and its unique receptor lymphotoxin β receptor (LTβR), play a pivotal role in the establishment and regulation of the immune system by allowing a tight communication between lymphocytes and stromal cells. Recent advances using transgenic mice harboring a specific deletion of the Ltbr gene in distinct stromal cells have revealed important roles for LTβR signaling in the thymic function that ensures the generation of a diverse and self-tolerant T-cell repertoire. In this review, we summarize our current knowledge on this signaling axis in the thymic homing of lymphoid progenitors and peripheral antigen-presenting cells, the trafficking and egress of thymocytes, the differentiation of medullary thymic epithelial cells, and the establishment of central tolerance. We also highlight the importance of LTα1β2/LTβR axis in controlling the recovery of the thymic function after myeloablative conditioning regimen, opening novel perspectives in regenerative medicine.Subject terms: Immune cell death, T cells     

Historical trends in frog populations in New Zealand based on public perceptions

Surveys were distributed to New Zealand land users in 1998 and 2008 to acquire information about New Zealand frogs with the aim of compiling and mapping their distribution and inferred population trends without costly and time-consuming field surveys. The overall frog population trend was reported as declining, with possible causes reported as an increase in agriculture, an increase in the distribution of predatory fish and disease. The resultant maps could be used for four main purposes: 1) to identify regions where Litoria populations are known to occur, which can be eliminated when considering suitable regions for translocation of Leiopelma; 2) to identify growing or stable populations of Litoria species, which may assist future disease surveys, population monitoring and to identify sources of genetic material that may serve as an Ark for declining Australian populations; 3) to highlight populations that are in decline to enable effective targeting of detailed disease studies; and 4) to approximate the stability of amphibian populations in the absence of more accurate, but costly, scientific monitoring.     

A novel harmony search-K means hybrid algorithm for clustering gene expression data

Recent progress in bioinformatics research has led to the accumulation of huge quantities of biological data at various data sources. The DNA microarray technology makes it possible to simultaneously analyze large number of genes across different samples. Clustering of microarray data can reveal the hidden gene expression patterns from large quantities of expression data that in turn offers tremendous possibilities in functional genomics, comparative genomics, disease diagnosis and drug development. The k- ¬means clustering algorithm is widely used for many practical applications. But the original k-¬means algorithm has several drawbacks. It is computationally expensive and generates locally optimal solutions based on the random choice of the initial centroids. Several methods have been proposed in the literature for improving the performance of the k-¬means algorithm. A meta-heuristic optimization algorithm named harmony search helps find out near-global optimal solutions by searching the entire solution space. Low clustering accuracy of the existing algorithms limits their use in many crucial applications of life sciences. In this paper we propose a novel Harmony Search-K means Hybrid (HSKH) algorithm for clustering the gene expression data. Experimental results show that the proposed algorithm produces clusters with better accuracy in comparison with the existing algorithms.     

Neurons controlling voluntary vocalization in the macaque ventral premotor cortex

The voluntary control of phonation is a crucial achievement in the evolution of speech. In humans, ventral premotor cortex (PMv) and Broca's area are known to be involved in voluntary phonation. In contrast, no neurophysiological data are available about the role of the oro-facial sector of nonhuman primates PMv in this function. In order to address this issue, we recorded PMv neurons from two monkeys trained to emit coo-calls. Results showed that a population of motor neurons specifically fire during vocalization. About two thirds of them discharged before sound onset, while the remaining were time-locked with it. The response of vocalization-selective neurons was present only during conditioned (voluntary) but not spontaneous (emotional) sound emission. These data suggest that the control of vocal production exerted by PMv neurons constitutes a newly emerging property in the monkey lineage, shedding light on the evolution of phonation-based communication from a nonhuman primate species.     

Glycosylation of Candida albicans Cell Wall Proteins Is Critical for Induction of Innate Immune Responses and Apoptosis of Epithelial Cells

C. albicans is one of the most common fungal pathogen of humans, causing local and superficial mucosal infections in immunocompromised individuals. Given that the key structure mediating host-C. albicans interactions is the fungal cell wall, we aimed to identify features of the cell wall inducing epithelial responses and be associated with fungal pathogenesis. We demonstrate here the importance of cell wall protein glycosylation in epithelial immune activation with a predominant role for the highly branched N-glycosylation residues. Moreover, these glycan moieties induce growth arrest and apoptosis of epithelial cells. Using an in vitro model of oral candidosis we demonstrate, that apoptosis induction by C. albicans wild-type occurs in early stage of infection and strongly depends on intact cell wall protein glycosylation. These novel findings demonstrate that glycosylation of the C. albicans cell wall proteins appears essential for modulation of epithelial immunity and apoptosis induction, both of which may promote fungal pathogenesis in vivo.     

Yeast populations associated with the artisanal cheese produced in the region of Serra da Canastra, Brazil

The aim of this work was to describe the yeast populations present during the manufacturing of Minas cheese of the region of Serra da Canastra, Minas Gerais state, Brazil. Canastra cheese is produced from raw cow’s milk at the farmhouse level using artisanal procedures and natural whey cultures as starters. Samples from 10 farms were studied, and they included: raw milk, natural starter, cheese curd before salting and cheese after 5 days of ripening. The most frequent yeasts in whey, curd and cheese were Debaryomyces hansenii, Kluyveromyces lactis, Kodamaea ohmeri and Torulaspora delbrueckii. Many yeast isolates were able to produce proteases, lipases and β-galactosidades. Production of these enzymes by yeasts in the cheese would contribute to the development of the characteristic flavor and smell during the ripening process.     

Fast-acting excitatory amino acids are involved in the enhancement of the aversiveness of the electrical stimulation of the inferior colliculus by systemic injections of muscimol

Gradual increases in the electrical stimulation of the inferior colliculus produces progressive aversive responses from vigilance, through freezing, until escape. These responses are probably mediated by excitatory amino acids (EAA) mechanisms as microinjection of glutamate into the inferior colliculus can trigger freezing responses while microinjections of NMDA cause a mixture of immobility and escape responses. Moreover, it has been shown that the neural substrates for defensive behavior in this structure are regulated by GABA-benzodiazepine mechanisms. Indeed, these responses are depressed by muscimol and midazolam locally injected into the inferior colliculus. In this work we were interested in knowing how GABAergic mechanisms interact with the EAA-mediated neural substrates of aversion generated at the inferior colliculus level. We found that while intraperitoneal injections of muscimol caused the expected antiaversive effects, unexpectedly systemic injections of muscimol enhanced the aversive reactions induced by electrical stimulation of the inferior colliculus of rats. Local injections into the central nucleus of the inferior colliculus of GDEE-an AMPA/kainate receptor antagonist-inhibited whereas AP7-a NMDA receptor antagonist-did not influence these responses. It is suggested that systemic injections of muscimol inhibit GABAergic inputs to the inferior colliculus. The removal of these inhibitory influences reduce the well-known tonic inhibitory control exerted by GABAergic mechanisms on the neural substrates of aversion of the inferior colliculus. Activation of these neural substrates by fast-acting AMPA/kainate receptors trigger the initial steps of the defense reaction in the central nucleus of the inferior colliculus.