927 research outputs found
VEGF and LPS synergistically silence inflammatory response to Plasmodium berghei infection and protect against cerebral malaria
No full textMalaria infection induces, alongside endothelial damage and obstruction hypoxia, a potent inflammatory response similar to that observed in other systemic diseases caused by bacteria and viruses. Accordingly, it is increasingly recognised that cerebral malaria (CM), the most severe and life threatening complication of Plasmodium falciparum infection, bears a number of similarities with sepsis, an often fatal condition associated with a misregulated inflammatory response triggered by systemic microbial infections.Using a Plasmodium berghei ANKA mouse model, histology, immunohistochemistry and gene expression analysis, we showed that lipopolysaccharide S (LPS), at doses that normally induce inflammation tolerance, protects P. berghei infected mice against experimental CM (ECM). Vascular endothelial growth factor (VEGF) preserved blood vessel integrity, and the combination with LPS resulted in a strong synergistic effect. Treated mice did not develop ECM, showed a prolonged survival and failed to develop a significant inflammatory response and splenomegaly in spite of normal parasite loads. The protective role of VEGF was further confirmed by the observation that the treatment of P. berghei infected C57BL/6 andBalb/c mice with the VEGF receptor inhibitor axitinib exacerbates cerebral pathology and aggravates the course of infection. Infected mice treated with VEGF and LPS showed an induction of the anti-inflammatory genes Nrf2 and HO-1 and a suppression to basal levels of the genes IFN-c and TNF-a. These results provide the rationale for developing new therapeutic approaches against CM and shed new light on how the inflammatory process can be modulated in the presence of systemic infectious diseases
Silencing of the Hsf gene, the transcriptional regulator of A. gambiae male accessory glands, inhibits the formation of the mating plug in mated females and disrupts their monogamous behaviour
No full textDiscovering the molecular factors that shape the mating behaviour and the fertility of the mosquito Anopheles gambiae, the principal vector of human malaria, is regarded as critical to better understand its reproductive success as well as for identifying new leads for malaria control measures. In A. gambiae mating induces complex behavioural and physiological changes in the females, including refractoriness to subsequent mating and induction of egg-laying. In other insects including Drosophila a group of proteins named Accessory gland proteins (Acps), produced by males and transferred with sperm to the female reproductive tract, have been implicated in this post-mating response. Although Acps represent a set of promising candidates for unravelling the mating physiology, their role in inducing behavioural changes in mated A. gambiae females remains largely unknown. In this work, we demonstrate that a down-regulation of a large fraction of Acp genes via silencing of the Acp regulating transcription factor Hsf, abolishes the formation of mating plug in mated females and fails to induce refractoriness of mated female to subsequent inseminations. A significant fraction of females mated to Hsf silenced males (66%) failed to receive the mating plug though seminal fluid had been transferred as documented by the presence of spermatozoa in the female sperm storage organ. Furthermore, nearly all females (95%) mated to HSF-silenced males were re-inseminated when exposed to males carrying EGPF marked sperm. Our findings provide evidence showing that Acp genes regulated by the transcription factor HSF play a key role in the function of the male accessory glands
Regulation of Anopheles gambiae male accessory gland genes influences postmating response in female.
No full textIn Drosophila, the accessory gland proteins (Acps) secreted from the male accessory glands (MAGs) and transferred along with sperm into the female reproductive tract have been implicated in triggering postmating behavioral changes, including refractoriness to subsequent mating and propensity to egg laying. Recently, Acps have been found also in Anopheles, suggesting similar functions. Understanding the mechanisms underlying transcriptional regulation of Acps and their functional role in modulating Anopheles postmating behavior may lead to the identification of novel vector control strategies to reduce mosquito populations. We identified heat-shock factor (HSF) binding sites within the Acp promoters of male Anopheles gambiae and discovered three distinct Hsf isoforms; one being significantly up-regulated in the MAGs after mating. Through genome-wide transcription analysis of Hsf-silenced males, we observed significant down-regulation in 50% of the Acp genes if compared to control males treated with a construct directed against an unrelated bacterial sequence. Treated males retained normal life span and reproductive behavior compared to control males. However, mated wild-type females showed a ∼46% reduction of egg deposition rate and a ∼23% reduction of hatching rate (∼58% combined reduction of progeny). Our results highlight an unsuspected role of HSF in regulating Acp transcription in A. gambiae and provide evidence that Acp down-regulation in males leads a significant reduction of progeny, thus opening new avenues toward the development of novel vector control strategies.-Dottorini, T., Persampieri, T., Palladino, P., Baker, D. A., Spaccapelo, R., Senin, N., Crisanti, A. Regulation of Anopheles gambiae male accessory gland genes influences postmating response in female
Gepoclu: a software tool for identifying and analyzing gene positional clusters in large-scale gene expression analysis
No full textAbstract Background The notion that genes are non-randomly organized within the chromosomes of eukaryotic organisms has recently received strong experimental support. Clusters of co-expressed and co-localized genes have been recognized as playing key roles in a number of functional pathways and adaptive responses including organism development, differentiation, disease states and aging. The identification of genes arranged in close proximity with each other within a particular temporal and spatial transcriptional program is anticipated to unravel possible functional links and reciprocal interactions. Results We developed a novel software tool Gepoclu (Gene Positional Clustering) that automatically selects genes based on expression values from multiple sources, including microarray, EST and qRT-PCR, and performs positional clustering. Gepoclu provides expression-based gene selection from multiple experimental sources, position-based gene clustering and cluster visualization functionalities, all as parts of the same fully integrated, and interactive, package. This means rapid iterations while exploring for emergent behavior, and full programmability of the filtering and clustering steps. Conclusions Gepoclu is a useful data-mining tool for exploring relationships among transcriptional data deriving form different sources. It provides an easy interactive environment for analyzing positional clustering behavior of co-expressed genes, and at the same time it is fully programmable, so that it can be customized and extended to support specific analysis needs.</p
CluGene: A Bioinformatics Framework for the Identification of Co-Localized, Co-Expressed and Co-Regulated Genes Aimed at the Investigation of Transcriptional Regulatory Networks from High-Throughput Expression Data
No full textThe full understanding of the mechanisms underlying transcriptional regulatory networks requires unravelling of complex causal relationships. Genome high-throughput technologies produce a huge amount of information pertaining gene expression and regulation; however, the complexity of the available data is often overwhelming and tools are needed to extract and organize the relevant information. This work starts from the assumption that the observation of co-occurrent events (in particular co-localization, co-expression and co-regulation) may provide a powerful starting point to begin unravelling transcriptional regulatory networks. Co-expressed genes often imply shared functional pathways; co-expressed and functionally related genes are often co-localized, too; moreover, co-expressed and co-localized genes are also potential targets for co-regulation; finally, co-regulation seems more frequent for genes mapped to proximal chromosome regions. Despite the recognized importance of analysing co-occurrent events, no bioinformatics solution allowing the simultaneous analysis of co-expression, co-localization and co-regulation is currently available. Our work resulted in developing and valuating CluGene, a software providing tools to analyze multiple types of co-occurrences within a single interactive environment allowing the interactive investigation of combined co-expression, co-localization and co-regulation of genes. The use of CluGene will enhance the power of testing hypothesis and experimental approaches aimed at unravelling transcriptional regulatory networks. The software is freely available at http://bioinfolab.unipg.it/
Functional cell permeable motifs within medically relevant proteins
No full textIncreasing experimental evidence indicates that short polybasic peptides are able to translocate across the membrane of living cells. However, these peptides, often derived from viruses and insects, may induce unspecific effects that could mask the action of their cargoes. Here, we show that a panel of lysine and/or arginine-rich peptides, derived from human proteins involved in cell signalling pathways leading to inflammation, possess the intrinsic ability to cross intact cellular membranes. These peptides are also capable of carrying a biologically active cargo. One of these peptides, encompassing the cell permeable sequence of the Toll-receptor 4 (TLR4) adaptor protein (TIRAP) and modified to carry a dominant-negative domain of the same TIRAP protein, selectively inhibited the production of pro-inflammatory cytokines upon LPS challenge, in in vitro, ex vivo and in vivo experiments. Docking studies indicated that this inhibition might be mediated by the disruption of the recruitment of downstream effector molecules. These results show for the first time the potential of using for therapy cell permeable peptides derived from human proteins involved in disease
Regulation of Anopheles gambiae male accessory gland genes influences postmating response in female
No full textIn Drosophila, the accessory gland proteins (Acps) secreted from the male accessory glands (MAGs) and transferred along with sperm into the female reproductive tract have been implicated in triggering postmating behavioral changes, including refractoriness to subsequent mating and propensity to egg laying. Recently, Acps have been found also in Anopheles, suggesting similar functions. Understanding the mechanisms underlying transcriptional regulation of Acps and their functional role in modulating Anoph-eles postmating behavior may lead to the identification of novel vector control strategies to reduce mosquito populations. We identified heat-shock factor (HSF) binding sites within the Acp promoters of male Anoph-eles gambiae and discovered three distinct Hsf isoforms; one being significantly up-regulated in the MAGs after mating. Through genome-wide transcription analysis of Hsf-silenced males, we observed significant down-regulation in 50% of the Acp genes if compared to control males treated with a construct directed against an unrelated bacterial sequence. Treated males retained normal life span and reproductive behavior compared to control males. However, mated wild-type females showed a 46% reduction of egg deposition rate and a 23% reduction of hatching rate (58% combined reduction of progeny). Our results highlight an unsus-pected role of HSF in regulating Acp transcription in A. gambiae and provide evidence that Acp down-regulation in males leads a significant reduction of progeny, thus opening new avenues toward the development of novel vector control strategies.—Dottorini, T., Persampieri, T.
La descrizione delle risorse bibliografiche in linked data
No full textThe article is an appendix of the volume Come lavorare con Wikidata in biblioteca = How to work with Wikidata in the library, written by Alessandra Boccone and Tania Maio, published by Editrice Bibliografica in April 2021. In this article, after a brief introduction to Wikidata and to the construction of an element, the tables of the WikiProject Books and Periodicals are reported. They have been translated, revised and expanded by the author, for the benefit of librarians who wish to approach the creation of items of bibliographic interest, such as authors, monographs, journals, articles in linked open data. It ends with a brief reflection on the possibilities offered by Wikidata in the field of authority control
A genome-wide analysis in Anopheles gambiae mosquitoes reveals 46 male accessory gland genes, possible modulators of female behaviour
No full textThe male accessory glands (MAGs) of many insect species produce and secrete a number of reproductive proteins collectively named Acps. These proteins, many of which are rapidly evolving, are essential for male fertility and represent formidable modulators of female postmating behavior. Upon copulation, the transfer of Acps has been shown in Drosophila and other insects to trigger profound physiological and behavioral changes in females, including enhanced ovulation/oviposition and reduced mating receptivity. In Anopheles gambiae mosquitoes, the principal vectors of human malaria, experimental evidence clearly demonstrates a key role of MAG products in inducing female responses. However, no Acp has been experimentally identified to date in this or in any other mosquito species. In this study we report on the identification of 46 MAG genes from An. gambiae, 25 of which are male reproductive tract-specific. This was achieved through a combination of bioinformatics searches and manual annotation confirmed by transcriptional profiling. Among these genes are the homologues of 40% of the Drosophila Acps analyzed, including Acp70A, or sex peptide, which in the fruit fly is the principal modulator of female postmating behavior. Although many Anopheles Acps belong to the same functional classes reported for Drosophila, suggesting a conserved role for these proteins in mosquitoes, some represent novel lineage-specific Acps that may have evolved to perform functions relevant to Anopheles reproductive behavior. Our findings imply that the molecular basis of Anopheles female postmating responses can now be studied, opening novel avenues for the field control of these important vectors of human disease
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