The human malaria parasite, Plasmodium falciparum, contains a non-photosynthetic and essential plastid called the apicoplast. This organelle is of major interest for its unique biology and potential as an attractive drug target. In this study, we characterize PfRAP03 and PfRAP08, two members of the RAP (RNA-binding domain abundant in apicomplexans) protein family.
View Article and Find Full Text PDFMitosis in eukaryotes involves reorganisation of the nuclear envelope (NE) and microtubule-organising centres (MTOCs). During male gametogenesis in , the causative agent of malaria, mitosis is exceptionally rapid and highly divergent. Within 8 min, the haploid male gametocyte genome undergoes three replication cycles (1N to 8N), while maintaining an intact NE.
View Article and Find Full Text PDFMitosis in eukaryotes involves reorganization of the nuclear envelope (NE) and microtubule-organizing centres (MTOCs). During male gametogenesis in Plasmodium, the causative agent of malaria, mitosis is exceptionally rapid and highly divergent. Within 8 min, the haploid male gametocyte genome undergoes three replication cycles (1N to 8N), while maintaining an intact NE.
View Article and Find Full Text PDFThe environmental challenges the human malaria parasite, , faces during its progression into its various lifecycle stages warrant the use of effective and highly regulated access to chromatin for transcriptional regulation. Microrchidia (MORC) proteins have been implicated in DNA compaction and gene silencing across plant and animal kingdoms. Accumulating evidence has shed light on the role MORC protein plays as a transcriptional switch in apicomplexan parasites.
View Article and Find Full Text PDFThe complex life cycle of Plasmodium falciparum requires coordinated gene expression regulation to allow host cell invasion, transmission, and immune evasion. Increasing evidence now suggests a major role for epigenetic mechanisms in gene expression in the parasite. In eukaryotes, many lncRNAs have been identified to be pivotal regulators of genome structure and gene expression.
View Article and Find Full Text PDFAnnu Rev Microbiol
September 2023
, the human malaria parasite, infects two hosts and various cell types, inducing distinct morphological and physiological changes in the parasite in response to different environmental conditions. These variations required the parasite to adapt and develop elaborate molecular mechanisms to ensure its spread and transmission. Recent findings have significantly improved our understanding of the regulation of gene expression in .
View Article and Find Full Text PDFThe human malaria parasites, including Plasmodium falciparum, persist as a major cause of global morbidity and mortality. The recent stalling of progress toward malaria elimination substantiates a need for novel interventions. Controlled gene expression is central to the parasite's numerous life cycle transformations and adaptation.
View Article and Find Full Text PDFAutophagy Rep
March 2023
Kinesins are microtubule (MT)-based motors important in cell division, motility, polarity, and intracellular transport in many eukaryotes. However, they are poorly studied in the divergent eukaryotic pathogens Plasmodium spp., the causative agents of malaria, which manifest atypical aspects of cell division and plasticity of morphology throughout the life cycle in both mammalian and mosquito hosts.
View Article and Find Full Text PDFFront Syst Biol
September 2022
The human malaria parasite, falciparum, is a unicellular protozoan responsible for over half a million deaths annually. With a complex life cycle alternating between human and invertebrate hosts, this apicomplexan is notoriously adept at evading host immune responses and developing resistance to all clinically administered treatments. Advances in omics-based technologies, increased sensitivity of sequencing platforms and enhanced CRISPR based gene editing tools, have given researchers access to more in-depth and untapped information about this enigmatic micro-organism, a feat thought to be infeasible in the past decade.
View Article and Find Full Text PDFGene families underlie genetic innovation and phenotypic diversification. However, our understanding of the early genomic and functional evolution of tandemly arranged gene families remains incomplete as paralog sequence similarity hinders their accurate characterization. The Drosophila melanogaster-specific gene family Sdic is tandemly repeated and impacts sperm competition.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
September 2019
The flagship member of the antiplasmodial isocyanoterpenes, 7,20-diisocyanoadociane (DICA), was synthesized from dehydrocryptone in 10 steps, and in 13 steps from commercially available material. Our previous formal synthesis was reengineered, leveraging only productive transformations to deliver DICA in fewer than half the number of steps of our original effort. Important contributions, in addition to the particularly concise strategy, include a solution to the problem of axial nucleophilic methylation of a late-stage cyclohexanone, and the first selective synthesis and antiplasmodial evaluation of the DICA stereoisomer with both isonitriles equatorial.
View Article and Find Full Text PDFThis article presents a high-level overview of the complex issues, opportunities, and challenges involved in improving child safety and preventing child maltreatment fatalities. It emphasizes that improving measurement and classification is critical to understanding and preventing child maltreatment fatalities. It also stresses the need to reframe child maltreatment interventions from a public health perspective.
View Article and Find Full Text PDFThis article highlights current models used in child protection to assess safety and risk, and discusses implications for child maltreatment fatalities. The authors advance that current risk and safety practice approaches were not designed to accurately estimate the likelihood of low base-rate phenomena and have not been empirically tested in their ability to predict or prevent severe or fatal child maltreatment. They advance that, regardless of the ultimate effectiveness of safety and risk tools, competent assessment and decision-making in child protection depend on sound professional judgment and a comprehensive systemic approach that transcends the use of specific tools.
View Article and Find Full Text PDFChild Welfare
March 2006
This article describes the efforts and special initiatives of New York City's Administration for Children's Services to improve services to immigrant and English language learner populations. Children's Services convened an immigration issues advisory subcommittee, created special tools for child welfare staff, collaborated with legal agencies to assist foster children with immigration status adjustments, improved agency data collection, and launched an agency-wide training initiative on immigration issues. The challenges encountered by Children's Services offer important insight for child welfare agencies in other jurisdictions designing strategies to strengthen their services for immigrant communities.
View Article and Find Full Text PDFThe New York City Administration for Children's Services (ACS) instituted a neighborhood-based services system through the realignment of all foster care, preventive, and protective services along community district lines. ACS, with its community partners, also formed neighborhood-based networks to improve service coordination and collaboration among key community stakeholders and to shape a multisystem strategy tailored to each district informed by child welfare data. Based on analysis of neighborhood-specific census tract child welfare data, ACS initiated the Community Partnership to Strengthen Families project to address the disproportionate number of foster care placements originating from a small group of high-need communities, including Manhattan's Central Harlem.
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