Publications by authors named "Leticia Anderson"

14 Publications

  • Page 1 of 1

Boundaries of Belonging: Theorizing Black African Migrant Experiences in Australia.

Int J Environ Res Public Health 2020 12 23;18(1). Epub 2020 Dec 23.

School of Arts and Social Science, Southern Cross University, Gold Coast, QLD 4225, Australia.

As nationalist ideologies intensify in Australia, so do the experiences of 'everyday racism' and exclusion for Black African immigrants. In this article, we utilize critical theories and engage with colonial histories to contextualize Afrodiasporic experiences in Australia, arguing that the conditional acceptance of Black bodies within Australian spaces is contingent upon the status quo of the white hegemony. The tropes and discourses that render the bodies of Black African migrants simultaneously invisible and hyper-visible indicate that immigration is not only a movement of bodies, but also a phenomenon solidly tied to global inequality, power, and the abjection of blackness. Drawing on critical race perspectives and theories of belonging, we highlight through use of literature how Black Africans in Australia are constructed as 'perpetual strangers'. As moral panics and discourses of hyper-criminality are summoned, the bordering processes are also simultaneously co-opted to reinforce scrutiny and securitization, with significant implications for social cohesion, belonging and public health.
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http://dx.doi.org/10.3390/ijerph18010038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793144PMC
December 2020

Druggable targets from coronaviruses for designing new antiviral drugs.

Bioorg Med Chem 2020 11 8;28(22):115745. Epub 2020 Sep 8.

Chemistry and Biotechnology Institute, Federal University of Alagoas, Campus A.C. Simões, Lourival Melo Mota Avenue, Maceió 57072-970, Brazil; Laboratory of Medicinal Chemistry, Pharmaceutical Sciences Institute, Federal University of Alagoas, Campus A.C. Simões, Lourival Melo Mota Avenue, Maceió 57072-970, Brazil. Electronic address:

Severe respiratory infections were highlighted in the SARS-CoV outbreak in 2002, as well as MERS-CoV, in 2012. Recently, the novel CoV (COVID-19) has led to severe respiratory damage to humans and deaths in Asia, Europe, and Americas, which allowed the WHO to declare the pandemic state. Notwithstanding all impacts caused by Coronaviruses, it is evident that the development of new antiviral agents is an unmet need. In this review, we provide a complete compilation of all potential antiviral agents targeting macromolecular structures from these Coronaviruses (Coronaviridae), providing a medicinal chemistry viewpoint that could be useful for designing new therapeutic agents.
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http://dx.doi.org/10.1016/j.bmc.2020.115745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836322PMC
November 2020

Retrospective clinical and epidemiological analysis of scorpionism at a referral hospital for the treatment of accidents by venomous animals in Alagoas State, Northeast Brazil, 2007-2017.

Rev Inst Med Trop Sao Paulo 2020 11;62:e26. Epub 2020 May 11.

Universidade Federal de Alagoas, Instituto de Ciências Biológicas e da Saúde, Laboratório de Pesquisas em Virologia e Imunologia, Grupo de Pesquisa em Regulação da Resposta Imune, Maceió, Alagoas, Brazil

Scorpionism has a high incidence rate in Brazil. It is considered a serious public health problem mainly in tropical and subtropical regions around the world. The number of scorpion accidents have increased over the years and the highest frequencies have been reported mainly in the Brazilian Northeast region. Therefore, in this study we report a retrospective clinical and epidemiological analysis of scorpion stings from 2007 to 2017 in Alagoas State, Northeast Brazil, at a referral hospital for assistance and treatment of accidents by venomous animals. During the analyzed period, the referral hospital treated 27,988 cases, and an increase in the number of cases has taken place over the years. The highest frequency of scorpion stings was observed in females, and the age range most affected was from 20 to 29 years old. The most stung body site was the foot, followed by finger, toe or hand. Regarding the severity, most severe cases were reported in children up to 4 years old (69.4%) and 50% of the total cases treated with serotherapy corresponded to patients in this age range. Interestingly, it was also found that the occurrence of systemic manifestations and the severity of the cases were significantly associated with pediatric patients. In this way, this study highlights the scorpionism as an environmental public health problem in Alagoas State, Northeast Brazil, as well as the need to intensify the epidemiological surveillance and educational campaigns to prevent and control scorpion accidents throughout the year.
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http://dx.doi.org/10.1590/s1678-9946202062026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232956PMC
May 2020

Cytokines and chemokines triggered by Chikungunya virus infection in human patients during the very early acute phase.

Trans R Soc Trop Med Hyg 2019 11;113(11):730-733

IMUNOREG-Grupo de Pesquisa em Regulação da Resposta Imune, Laboratório de Pesquisas em Virologia e Imunologia, Instituto de Ciências Biológicas e da Saúde, Universidade Federal de Alagoas, Maceió, Alagoas, Brazil.

Background: The immune response against the Chikungunya virus (CHIKV) during the very early acute phase is not fully elucidated. Therefore we explored the cytokine and chemokine profile triggered by CHIKV in infected patients.

Methods: Cytokines, chemokines and C5a anaphylatoxin were analysed in serum from CHIKV-infected patients during the viraemic phase (mean 2.97±1.27 d after illness onset) compared with a healthy group.

Results: CHIKV-infected patients had a significant increase of interferon-α (IFN-α), interleukin-6 (IL-6), interleukin-8 (CXCL8/IL-8), interleukin-10 (IL-10), interferon-γ (IFN-γ), monokine induced by interferon-γ (CXCL9/MIG), monocyte chemoattractant protein-1 (CCL2/MCP-1), interferon-γ-induced protein-10 (CXCL10/IP-10) and complement C5a anaphylatoxin.

Conclusions: The very early acute immune response triggered against CHIKV leads to an increase in pro-inflammatory immune mediators such as IFN-γ and its induced chemokines, and a high level of C5a anaphylatoxin as a result of complement activation.
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http://dx.doi.org/10.1093/trstmh/trz065DOI Listing
November 2019

Cellular and Molecular Immune Response to Chikungunya Virus Infection.

Front Cell Infect Microbiol 2018 10;8:345. Epub 2018 Oct 10.

IMUNOREG-Grupo de Pesquisa em Regulação da Resposta Imune, Laboratório de Pesquisas em Virologia e Imunologia, Instituto de Ciências Biológicas e da Saúde, Universidade Federal de Alagoas, Maceió, Brazil.

Chikungunya virus (CHIKV) is a re-emergent arthropod-borne virus (arbovirus) that causes a disease characterized primarily by fever, rash and severe persistent polyarthralgia. In the last decade, CHIKV has become a serious public health problem causing several outbreaks around the world. Despite the fact that CHIKV has been around since 1952, our knowledge about immunopathology, innate and adaptive immune response involved in this infectious disease is incomplete. In this review, we provide an updated summary of the current knowledge about immune response to CHIKV and about soluble immunological markers associated with the morbidity, prognosis and chronicity of this arbovirus disease. In addition, we discuss the progress in the research of new vaccines for preventing CHIKV infection and the use of monoclonal antibodies as a promising therapeutic strategy.
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http://dx.doi.org/10.3389/fcimb.2018.00345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191487PMC
September 2019

Report of East-Central South African Chikungunya virus genotype during the 2016 outbreak in the Alagoas State, Brazil.

Rev Inst Med Trop Sao Paulo 2018 23;60:e19. Epub 2018 Apr 23.

Laboratório de Pesquisas em Virologia e Imunologia (LAPEVI), Grupo de Pesquisa em Regulação da Resposta Imune (IMUNOREG), Instituto de Ciências Biológicas e da Saúde (ICBS), Universidade Federal de Alagoas, Maceió, Alagoas, Brazil.

Chikungunya virus (CHIKV) causes a self-limiting disease characterized by the onset of fever, skin rash and persistent arthralgia. In the last decade, it has emerged as a serious public health problem causing several outbreaks around the world. Here, we report the CHIKV genotype characterization during the 2016 CHIKV outbreak in Alagoas State, Brazil. Partial E1 sequence from CHIKV-positive samples coming from different cities of Alagoas were submitted to DNA sequencing followed by phylogenetic analysis thus characterizing the virus genotype. The circulating CHIKV virus in Alagoas during 2016 outbreak belongs to the East-Central South African genotype. In this way, virus genotyping to monitoring the spread of CHIKV is needed to continued surveillance supporting the development of prevention strategies, mainly in endemic areas of mosquitoes and arboviruses co-circulation.
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http://dx.doi.org/10.1590/s1678-9946201860019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956549PMC
May 2018

Histone deacetylase inhibition modulates histone acetylation at gene promoter regions and affects genome-wide gene transcription in Schistosoma mansoni.

PLoS Negl Trop Dis 2017 04 13;11(4):e0005539. Epub 2017 Apr 13.

Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.

Background: Schistosomiasis is a parasitic disease infecting hundreds of millions of people worldwide. Treatment depends on a single drug, praziquantel, which kills the Schistosoma spp. parasite only at the adult stage. HDAC inhibitors (HDACi) such as Trichostatin A (TSA) induce parasite mortality in vitro (schistosomula and adult worms), however the downstream effects of histone hyperacetylation on the parasite are not known.

Methodology/principal Findings: TSA treatment of adult worms in vitro increased histone acetylation at H3K9ac and H3K14ac, which are transcription activation marks, not affecting the unrelated transcription repression mark H3K27me3. We investigated the effect of TSA HDACi on schistosomula gene expression at three different time points, finding a marked genome-wide change in the transcriptome profile. Gene transcription activity was correlated with changes on the chromatin acetylation mark at gene promoter regions. Moreover, combining expression data with ChIP-Seq public data for schistosomula, we found that differentially expressed genes having the H3K4me3 mark at their promoter region in general showed transcription activation upon HDACi treatment, compared with those without the mark, which showed transcription down-regulation. Affected genes are enriched for DNA replication processes, most of them being up-regulated. Twenty out of 22 genes encoding proteins involved in reducing reactive oxygen species accumulation were down-regulated. Dozens of genes encoding proteins with histone reader motifs were changed, including SmEED from the PRC2 complex. We targeted SmEZH2 methyltransferase PRC2 component with a new EZH2 inhibitor (GSK343) and showed a synergistic effect with TSA, significantly increasing schistosomula mortality.

Conclusions/significance: Genome-wide gene expression analyses have identified important pathways and cellular functions that were affected and may explain the schistosomicidal effect of TSA HDACi. The change in expression of dozens of histone reader genes involved in regulation of the epigenetic program in S. mansoni can be used as a starting point to look for possible novel schistosomicidal targets.
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http://dx.doi.org/10.1371/journal.pntd.0005539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5404884PMC
April 2017

A Regulatory miRNA-mRNA Network Is Associated with Tissue Repair Induced by Mesenchymal Stromal Cells in Acute Kidney Injury.

Front Immunol 2016 3;7:645. Epub 2017 Jan 3.

Departamento de Medicina, Divisão de Nefrologia, Universidade Federal de São Paulo, São Paulo, Brazil; Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.

Mesenchymal stromal cells (MSCs) orchestrate tissue repair by releasing cell-derived microvesicles (MVs), which, presumably by small RNA species, modulate global gene expression. The knowledge of miRNA/mRNA signatures linked to a reparative status may elucidate some of the molecular events associated with MSC protection. Here, we used a model of cisplatin-induced kidney injury (acute kidney injury) to assess how MSCs or MVs could restore tissue function. MSCs and MVs presented similar protective effects, which were evidenced and by modulating apoptosis, inflammation, oxidative stress, and a set of prosurvival molecules. In addition, we observed that miRNAs (i.e., miR-880, miR-141, miR-377, and miR-21) were modulated, thereby showing active participation on regenerative process. Subsequently, we identified that MSC regulates a particular miRNA subset which mRNA targets are associated with Wnt/TGF-β, fibrosis, and epithelial-mesenchymal transition signaling pathways. Our results suggest that MSCs release MVs that transcriptionally reprogram injured cells, thereby modulating a specific miRNA-mRNA network.
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http://dx.doi.org/10.3389/fimmu.2016.00645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5206861PMC
January 2017

Interaction of an esophageal MEG protein from schistosomes with a human S100 protein involved in inflammatory response.

Biochim Biophys Acta Gen Subj 2017 Jan 15;1861(1 Pt A):3490-3497. Epub 2016 Sep 15.

Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, Brazil. Electronic address:

Background: The Micro-Exon Gene-14 (MEG-14) displays a remarkable structure that allows the generation of antigenic variation in Schistosomes. Previous studies showed that the soluble portion of the MEG-14 protein displays features of an intrinsically disordered protein and is expressed exclusively in the parasite esophageal gland. These features indicated a potential for interaction with host proteins present in the plasma and cells from ingested blood.

Methods: A yeast two-hybrid experiment using as bait the soluble domain of Schistosoma mansoni MEG-14 (sMEG-14) against a human leukocyte cDNA library was performed. Pull-down and surface plasmon resonance (SPR) experiments were used to validate the interaction between sMEG-14 and human S100A9. Synchrotron radiation circular dichroism (SRCD) were used to detect structural changes upon interaction between sMEG-14 and human S100A9. Feeding of live parasites with S100A9 attached to a fluorophore allowed the tracking of the fate of this protein in the parasite digestive system.

Results: S100A9 interacted with sMEG-14 consistently in yeast two-hybrid assay, pull-down and SPR experiments. SRCD suggested that MEG-14 acquired a more regular structure as a result of the interaction with S100A9. Accumulation of recombinant S100A9 in the parasite's esophageal gland, when ingested by live worms suggests that such interaction may occur in vivo.

Conclusion: S100A9, a protein previously described to be involved in modulation of inflammatory response, was found to interact with sMEG-14.

General Significance: Our results allow proposing a mechanism involving MEG-14 for the parasite to block inflammatory signaling, which would occur upon release of S100A9 when ingested blood cells are lysed.
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http://dx.doi.org/10.1016/j.bbagen.2016.09.015DOI Listing
January 2017

HIPSTR and thousands of lncRNAs are heterogeneously expressed in human embryos, primordial germ cells and stable cell lines.

Sci Rep 2016 09 8;6:32753. Epub 2016 Sep 8.

Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, 05508-000 São Paulo, SP, Brazil.

Eukaryotic genomes are transcribed into numerous regulatory long non-coding RNAs (lncRNAs). Compared to mRNAs, lncRNAs display higher developmental stage-, tissue-, and cell-subtype-specificity of expression, and are generally less abundant in a population of cells. Despite the progress in single-cell-focused research, the origins of low population-level expression of lncRNAs in homogeneous populations of cells are poorly understood. Here, we identify HIPSTR (Heterogeneously expressed from the Intronic Plus Strand of the TFAP2A-locus RNA), a novel lncRNA gene in the developmentally regulated TFAP2A locus. HIPSTR has evolutionarily conserved expression patterns, its promoter is most active in undifferentiated cells, and depletion of HIPSTR in HEK293 and in pluripotent H1BP cells predominantly affects the genes involved in early organismal development and cell differentiation. Most importantly, we find that HIPSTR is specifically induced and heterogeneously expressed in the 8-cell-stage human embryos during the major wave of embryonic genome activation. We systematically explore the phenomenon of cell-to-cell variation of gene expression and link it to low population-level expression of lncRNAs, showing that, similar to HIPSTR, the expression of thousands of lncRNAs is more highly heterogeneous than the expression of mRNAs in the individual, otherwise indistinguishable cells of totipotent human embryos, primordial germ cells, and stable cell lines.
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http://dx.doi.org/10.1038/srep32753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015059PMC
September 2016

Schistosoma mansoni Egg, Adult Male and Female Comparative Gene Expression Analysis and Identification of Novel Genes by RNA-Seq.

PLoS Negl Trop Dis 2015 Dec 31;9(12):e0004334. Epub 2015 Dec 31.

Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.

Background: Schistosomiasis is one of the most prevalent parasitic diseases worldwide and is a public health problem. Schistosoma mansoni is the most widespread species responsible for schistosomiasis in the Americas, Middle East and Africa. Adult female worms (mated to males) release eggs in the hepatic portal vasculature and are the principal cause of morbidity. Comparative separate transcriptomes of female and male adult worms were previously assessed with using microarrays and Serial Analysis of Gene Expression (SAGE), thus limiting the possibility of finding novel genes. Moreover, the egg transcriptome was analyzed only once with limited bacterially cloned cDNA libraries.

Methodology/principal Findings: To compare the gene expression of S. mansoni eggs, females, and males, we performed RNA-Seq on these three parasite forms using 454/Roche technology and reconstructed the transcriptome using Trinity de novo assembly. The resulting contigs were mapped to the genome and were cross-referenced with predicted Smp genes and H3K4me3 ChIP-Seq public data. For the first time, we obtained separate, unbiased gene expression profiles for S. mansoni eggs and female and male adult worms, identifying enriched biological processes and specific enriched functions for each of the three parasite forms. Transcripts with no match to predicted genes were analyzed for their protein-coding potential and the presence of an encoded conserved protein domain. A set of 232 novel protein-coding genes with putative functions related to reproduction, metabolism, and cell biogenesis was detected, which contributes to the understanding of parasite biology.

Conclusions/significance: Large-scale RNA-Seq analysis using de novo assembly associated with genome-wide information for histone marks in the vicinity of gene models constitutes a new approach to transcriptome analysis that has not yet been explored in schistosomes. Importantly, all data have been consolidated into a UCSC Genome Browser search- and download-tool (http://schistosoma.usp.br/). This database provides new ways to explore the schistosome genome and transcriptome and will facilitate molecular research on this important parasite.
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http://dx.doi.org/10.1371/journal.pntd.0004334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699917PMC
December 2015

Synergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms.

PLoS Negl Trop Dis 2015 24;9(9):e0004086. Epub 2015 Sep 24.

Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil; Instituto Butantan, São Paulo, São Paulo, Brazil.

Background: Treatment and morbidity control of schistosomiasis relies on a single drug, praziquantel (PZQ), and the selection of resistant worms under repeated treatment is a concern. Therefore, there is a pressing need to understand the molecular effects of PZQ on schistosomes and to investigate alternative or synergistic drugs against schistosomiasis.

Methodology: We used a custom-designed Schistosoma mansoni expression microarray to explore the effects of sublethal doses of PZQ on large-scale gene expression of adult paired males and females and unpaired mature females. We also assessed the efficacy of PZQ, omeprazole (OMP) or their combination against S. mansoni adult worms with a survival in vitro assay.

Principal Findings: We identified sets of genes that were affected by PZQ in paired and unpaired mature females, however with opposite gene expression patterns (up-regulated in paired and down-regulated in unpaired mature females), indicating that PZQ effects are heavily influenced by the mating status. We also identified genes that were similarly affected by PZQ in males and females. Functional analyses of gene interaction networks were performed with parasite genes that were differentially expressed upon PZQ treatment, searching for proteins encoded by these genes whose human homologs are targets of different drugs used for other diseases. Based on these results, OMP, a widely prescribed proton pump inhibitor known to target the ATP1A2 gene product, was chosen and tested. Sublethal doses of PZQ combined with OMP significantly increased worm mortality in vitro when compared with PZQ or OMP alone, thus evidencing a synergistic effect.

Conclusions: Functional analysis of gene interaction networks is an important approach that can point to possible novel synergistic drug candidates. We demonstrated the potential of this strategy by showing that PZQ in combination with OMP displayed increased efficiency against S. mansoni adult worms in vitro when compared with either drug alone.
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http://dx.doi.org/10.1371/journal.pntd.0004086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581627PMC
March 2016

Schistosoma mansoni histones: from transcription to chromatin regulation; an in silico analysis.

Mol Biochem Parasitol 2012 Jun 10;183(2):105-14. Epub 2012 Mar 10.

Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, 05508-000 São Paulo, SP, Brazil.

Schistosoma mansoni is a human endoparasite with a complex life cycle that also infects an invertebrate mollusk intermediate host and exhibits many diverse phenotypes. Its complexity is reflected in a large genome and different transcriptome profiles specific to each life cycle stage. Epigenetic regulation of gene expression such as the post-translational modification of histones has a significant impact on phenotypes, and this information storage function resides primarily at histone tails, which results in a varied histone code. Evidence of transcription of the different histone families at all life stages of the parasite was detected by a survey of transcriptome databases; manual curation of each gene prediction at the genome sequence level showed errors in the coding sequences of three of them. The biogenesis of histones is coupled to DNA replication, and a detailed in silico analysis of the specialized machinery of histone mRNA processing in the S. mansoni genome reveals that it is as conserved as in other eukaryotes, consisting in transcription factors and stem-loop binding proteins which recognize the stem loop structure at the histone mRNA 3'UTR. Histone modifying enzymes (HMEs) such as histone acetyltransferases, methyltransferases and deacetylases (HDACs) have been described in S. mansoni, and their potential as new therapeutic targets was evidenced with the apoptotic phenotype that resulted from HDAC inhibition. However, the overall regulation of transcription coupled with gene expression profiles correlated to histone modifications has not yet been characterized. Besides the interaction of HMEs with histones, many factors involved in cellular processes are known to bind to histones, and were identified here by an in silico analysis of the S. mansoni genome. Knowledge of the histone families opens up perspectives for further studies that will lead to a better identification of their post-translational modifications, their gene regulation and to the possible characterization of HMEs as targets for the development of new drugs.
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http://dx.doi.org/10.1016/j.molbiopara.2012.03.001DOI Listing
June 2012