The Toxoplasma rhoptry protein ROP55 is a major virulence factor that prevents lytic host cell death.

Programmed-cell death is an antimicrobial defense mechanism that promotes clearance of intracellular pathogens. Toxoplasma counteracts host immune defenses by secreting effector proteins into host cells; however, how the parasite evades lytic cell death and the effectors involved remain poorly characterized. We identified ROP55, a rhoptry protein that promotes parasite survival by preventing lytic cell death in absence of IFN-γ stimulation.

A novel SUN1-ALLAN complex coordinates segregation of the bipartite MTOC across the nuclear envelope during rapid closed mitosis in Plasmodium.

Mitosis in eukaryotes involves reorganization of the nuclear envelope (NE) and microtubule-organizing centres (MTOCs). In , the causative agent of malaria, male gametogenesis mitosis is exceptionally rapid and divergent. Within 8 minutes, the haploid male gametocyte genome undergoes three replication cycles (1N to 8N), while maintaining an intact NE.

MORC protein regulates chromatin accessibility and transcriptional repression in the human malaria parasite, .

The 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.

A kalihinol analog disrupts apicoplast function and vesicular trafficking in malaria.

We report the discovery of MED6-189, an analog of the kalihinol family of isocyanoterpene natural products that is effective against drug-sensitive and drug-resistant strains, blocking both asexual replication and sexual differentiation. In vivo studies using a humanized mouse model of malaria confirm strong efficacy of the compound in animals with no apparent hemolytic activity or toxicity. Complementary chemical, molecular, and genomics analyses revealed that MED6-189 targets the parasite apicoplast and acts by inhibiting lipid biogenesis and cellular trafficking.

Insights into the evolution, virulence and speciation of and through multiomics analyses.

Babesiosis, caused by protozoan parasites of the genus , is an emerging tick-borne disease of significance for both human and animal health. parasites infect erythrocytes of vertebrate hosts where they develop and multiply rapidly to cause the pathological symptoms associated with the disease. The identification of new species underscores the ongoing risk of zoonotic pathogens capable of infecting humans, a concern amplified by anthropogenic activities and environmental changes.

Psychosocial impacts of Baby Friendly Spaces for Rohingya refugee mothers in Bangladesh: A pragmatic cluster-randomized controlled trial.

Background: This study evaluated the effectiveness of Baby Friendly Spaces (BFS), a psychosocial support program for Rohingya refugee mothers of malnourished young children in Bangladesh. Because BFS was already being implemented, we examined the benefit of enhancing implementation supports.

Methods: In matched pairs, 10 sites were randomized to provide BFS treatment as usual (BFS-TAU) or to receive enhanced implementation support (BFS-IE).

The Toxoplasma gondii F-Box Protein L2 Functions as a Repressor of Stage Specific Gene Expression.

Toxoplasma gondii is a foodborne pathogen that can cause severe and life-threatening infections in fetuses and immunocompromised patients. Felids are its only definitive hosts, and a wide range of animals, including humans, serve as intermediate hosts. When the transmissible bradyzoite stage is orally ingested by felids, they transform into merozoites that expand asexually, ultimately generating millions of gametes for the parasite sexual cycle.

Chromatin structure and - a tango in regulation of gene expression in the human malaria parasite, ?

Over the last few decades, novel methods have been developed to study how chromosome positioning within the nucleus may play a role in gene regulation. Adaptation of these methods in the human malaria parasite, , has recently led to the discovery that the three-dimensional structure of chromatin within the nucleus may be critical in controlling expression of virulence genes ( genes). Recent work has implicated an unusual, highly conserved gene called in contributing to coordinated transcriptional switching, however how this gene functions in this capacity is unknown.

Proteome-Wide Identification of RNA-dependent proteins and an emerging role for RNAs in Plasmodium falciparum protein complexes.

Ribonucleoprotein complexes are composed of RNA, RNA-dependent proteins (RDPs) and RNA-binding proteins (RBPs), and play fundamental roles in RNA regulation. However, in the human malaria parasite, Plasmodium falciparum, identification and characterization of these proteins are particularly limited. In this study, we use an unbiased proteome-wide approach, called R-DeeP, a method based on sucrose density gradient ultracentrifugation, to identify RDPs.

Multiomics analysis reveals MO1 as a distinct species and provides insights into its evolution and virulence.

Babesiosis, caused by protozoan parasites of the genus , is an emerging tick-borne disease of significance for both human and animal health. parasites infect erythrocytes of vertebrate hosts where they develop and multiply rapidly to cause the pathological symptoms associated with the disease. The identification of various species underscores the ongoing risk of new zoonotic pathogens capable of infecting humans, a concern amplified by anthropogenic activities and environmental shifts impacting the distribution and transmission dynamics of parasites, their vectors, and reservoir hosts.

F-Box Protein L2 Silences Feline-Restricted Genes Necessary for Sexual Commitment.

is a foodborne pathogen that can cause severe and life-threatening infections in fetuses and immunocompromised patients. Felids are its only definitive hosts, and a wide range of animals, including humans, serve as intermediate hosts. When the transmissible bradyzoite stage is orally ingested by felids, they transform into merozoites that expand asexually, ultimately generating millions of gametes for the parasite sexual cycle.

Mapping the association between mental health and people's perceived and actual ability to practice hygiene-related behaviours in humanitarian and pandemic crises: A scoping review.

Humanitarian crises such as disease outbreaks, conflict and displacement and natural disasters affect millions of people primarily in low- and middle-income countries. Here, they often reside in areas with poor environmental health conditions leading to an increased burden of infectious diseases such as gastrointestinal and respiratory infections. Water, sanitation, and hygiene behaviours are critical to prevent such infections and deaths.

A Potent Kalihinol Analogue Disrupts Apicoplast Function and Vesicular Trafficking in Malaria.

Here we report the discovery of MED6-189, a new analogue of the kalihinol family of isocyanoterpene (ICT) natural products. MED6-189 is effective against drug-sensitive and -resistant strains blocking both intraerythrocytic asexual replication and sexual differentiation. This compound was also effective against and .

DNA-binding protein PfAP2-P regulates parasite pathogenesis during malaria parasite blood stages.

Malaria-associated pathogenesis such as parasite invasion, egress, host cell remodelling and antigenic variation requires concerted action by many proteins, but the molecular regulation is poorly understood. Here we have characterized an essential Plasmodium-specific Apicomplexan AP2 transcription factor in Plasmodium falciparum (PfAP2-P; pathogenesis) during the blood-stage development with two peaks of expression. An inducible knockout of gene function showed that PfAP2-P is essential for trophozoite development, and critical for var gene regulation, merozoite development and parasite egress.

MORC protein regulates chromatin accessibility and transcriptional repression in the human malaria parasite, .

The 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 into the role MORC protein plays as a transcriptional switch in apicomplexan parasites.

Sex determination and transmission: Leveraging genetic screens to reveal Plasmodium's secrets.

Genes and regulatory mechanisms governing malaria parasite transmission and development in mosquitoes are incompletely understood. Recently, Russell and colleagues identified genes required for parasite sexual development. In this issue of Cell Host & Microbe, Ukegbu and colleagues report a genetic approach to study genes enabling parasite survival in mosquito stages.

An model of recrudescence reveals developmental plasticity of the bradyzoite stage.

The classical depiction of the lifecycle is bradyzoite excystation conversion to tachyzoites, cell lysis, and immune control, followed by the reestablishment of bradyzoites and cysts. In contrast, we show that tachyzoite growth slows independent of the host immune response at a predictable time point following excystation. Furthermore, we demonstrate a host cell-dependent pathway of continuous amplification of the cyst-forming bradyzoite population.

Methodological choices for an economic evaluation of a combined psychosocial and nutrition treatment intervention for children with severe acute malnutrition: The FUSAM trial in Nepal.

As a public health burden, severe acute malnutrition (SAM) among children has been increasingly studied to determine the optimal combination of treatment approaches. Among the new approaches is the addition of early childhood development sessions to standard nutrition-based treatment for SAM which can enhance both nutrition and development outcomes among young children. However, few studies demonstrate the relationship between the costs of such combined programs and the benefits accrued to the children and their caregivers.

Novel insights into the role of long non-coding RNA in the human malaria parasite, Plasmodium falciparum.

The 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.

Mental health and psychosocial support in response to onset of the COVID-19 pandemic: Emotional and Stress Management Intervention in Liberia, Sierra Leone, and Ivory Coast.

Background: In response to the psychological distress experienced by people affected by the onset of the COVID-19 pandemic, Action Against Hunger (Action contre la Faim, ACF) developed and implemented the Emotional and Stress Management Intervention (ESMI) in Liberia, Sierra Leone, and Ivory Coast. ESMI is a person-to-person two-session, non-specialized, mental health and psychosocial support intervention for adults and adolescents in the general population based in problem solving therapy and principles of emotional regulation.

Methods: Using de-identified programmatic data for each country, we conducted paired t-tests to assess whether adults and adolescents who received ESMI experienced changes in reported psychological distress and perceived social support following the intervention.

Small RNA sequencing of field Culex mosquitoes identifies patterns of viral infection and the mosquito immune response.

Mosquito-borne disease remains a significant burden on global health. In the United States, the major threat posed by mosquitoes is transmission of arboviruses, including West Nile virus by mosquitoes of the Culex genus. Virus metagenomic analysis of mosquito small RNA using deep sequencing and advanced bioinformatic tools enables the rapid detection of viruses and other infecting organisms, both pathogenic and non-pathogenic to humans, without any precedent knowledge.

PfAP2-MRP DNA-binding protein is a master regulator of parasite pathogenesis during malaria parasite blood stages.

Malaria pathogenicity results from the parasite's ability to invade, multiply within and then egress from the host red blood cell (RBC). Infected RBCs are remodeled, expressing antigenic variant proteins (such as PfEMP1, coded by the gene family) for immune evasion and survival. These processes require the concerted actions of many proteins, but the molecular regulation is poorly understood.

Epigenetic Regulation and Chromatin Remodeling in Malaria Parasites.

, 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 .