Parasite master

The human malaria parasite Plasmodium falciparum represses transcription of the gene encoding AP2-G, which is the master regulator of germ cell differentiation, via heterochromatin condensation following histone H3 lysine 9 trimethylation (H3K9me3). Although H3K9me3-marked heterochromatin is typically constitutive and its establishment depends on the RNA interference (RNAi) pathway in fission yeast centromeres, malaria parasites lack molecular members essential for RNAi. We developed a strategy to assess heterochromatin establishment on artificial chromosomes introduced into P...

Cluster of differentiation (CD4+ ) T cells consist of multiple subtypes, defined by expression of lineage-specific transcription factors, that contribute to the control of infectious diseases by providing help to immune and nonimmune target cells. In the current study, we examined the role of B cell lymphoma (Bcl)-6, a transcriptional repressor and master regulator of T follicular helper cell differentiation, in T cell-mediated host defense against intestinal and systemic parasitic infections. We demonstrate that while Bcl-6 expression by CD4+ T cells is critical for antibody-mediated protective immunity against secondary infection with the nematode Heligmosoides polygyrus bakeri, it paradoxically compromises worm expulsion during primary infection by limiting the generation of interleukin-10 (IL-10)-producing Gata3+ T helper 2 cells...

Treponema pallidum (Tp) has a well-known ability to evade the immune system and can cause neurosyphilis by invading the central nervous system (CNS). Microglia are resident macrophages of the CNS that are essential for host defense against pathogens, this study aims to investigate the interaction between Tp and microglia and the potential mechanism. Here, we found that Tp can exert significant toxic effects on microglia in vivo in Tg (mpeg1: EGFP) transgenic zebrafish embryos. Single-cell RNA sequencing results showed that Tp downregulated autophagy-related genes in human HMC3 microglial cells, which is negatively associated with apoptotic gene expression...

Multi-chromosomal mitochondrial genome (mitogenome) structures have repeatedly evolved in many lineages of angiosperms. However, the underlying mechanism remains unclear. The mitogenomes of three genera of Balanophoraceae, namely Lophophytum, Ombrophytum and Rhopalocnemis, have already been sequenced and assembled, all showing a highly multi-chromosomal structure, albeit with different genome and chromosome sizes. It is expected that characterization of additional lineages of this family may expand the knowledge of mitogenome diversity and provide insights into the evolution of plant mitogenome structure and size...

Despite the introduction of novel treatment strategies, management of rheumatic disorders remains associated with substantial unmet clinical need. Of interest therefore, it has recently become apparent that there is a global inverse relationship between the incidence of such conditions and parasitic helminth infection, with striking examples involving rheumatoid arthritis (RA)/systemic lupus erythematosus (SLE) patients and filarial nematode worm infection in studies in India. Such findings reflect that helminths are master manipulators of the immune system, particularly in being able to modulate proinflammatory responses...

In this paper, we report on a high-power and widely tunable thulium-doped fiber laser (TDFL) based on a monolithic master oscillator power amplifier (MOPA) system. The master oscillator is a Tm fiber ring laser incorporating a tunable bandpass filter to realize narrow linewidth and wavelength tunable operation. The MOPA generated 1010 W ∼1039 W of output power over a tuning range of 107 nm from 1943 to 2050nm with slope efficiencies of more than 51% and spectra linewidth of ∼0.5 nm...

Transposable elements (TEs) are obligate genomic parasites, relying on host germline cells to ensure their replication and passage to future generations. While some TEs exhibit high fidelity to their host genome, being passed from parent to offspring through vertical transmission for millions of years, others frequently invade new and distantly related hosts through horizontal transfer. In this review, I highlight how the complexity of interactions between TE and host required for transposition may be an important determinant of horizontal transfer: with TEs with more complex regulatory requirements being less able to invade new host genomes...

Trypanosoma brucei is a single celled eukaryotic parasite in the group of the Kinetoplastea. The parasite harbors a single mitochondrion with a singular mitochondrial genome that is known as the kinetoplast DNA (kDNA). The kDNA consists of a unique network of thousands of interlocked circular DNA molecules. To ensure proper inheritance of the kDNA to the daughter cells, the genome is physically linked to the basal body, the master organizer of the cell cycle in trypanosomes. The connection that spans, cytoplasm, mitochondrial membranes and the mitochondrial matrix is mediated by the Tripartite Attachment Complex (TAC)...

By converging advanced science, engineering, and design, deep techs are bringing a great wave of future innovations by mastering challenges and problem complexity across sectors and the field of parasitology is no exception. Remarkable research and advancements can be seen in the field of parasite detection and diagnosis through smartphone applications. Supervised and unsupervised data deep learnings are heavily exploited for the development of automated neural network models for the prediction of parasites, eggs, etc...

Trypanosomatids are a diverse family of protozoan parasites, some of which cause devastating human and livestock diseases. There are two distinct infection life cycles in trypanosomatids; some species complete their entire life cycle in a single host (monoxenous) while others infect two hosts (dixenous). Dixenous trypanosomatids are mostly vectored by insects, and the human trypanosomatid diseases are caused mainly by vectored parasites. While infection prevalence has been described for subsets of hosts and trypanosomatids, little is known about whether monoxenous and dixenous trypanosomatids differ in infection prevalence...

Structured light beams that are tailored for purpose have found a myriad of applications, from improved efficiency of laser-based industrial manufacturing processes to enhanced bandwidth in optical communication. While the selection of such modes is readily achievable at low powers (<100 mW) with external shaping devices, creating and controlling structured light at higher powers (>1 W) has proven to be a non-trivial task, particularly if dynamic control is required. Here we demonstrate the power amplification of low-power higher-order Laguerre-Gaussian modes using a novel in-line dual-pass master oscillator power amplifier (MOPA)...

Body tissues are subjected to various oxygenic gradients and fluctuations and hence can become transiently hypoxic. Hypoxia-inducible factor (HIF) is the master transcriptional regulator of the cellular hypoxic response and is capable of modulating cellular metabolism, immune responses, epithelial barrier integrity, and local microbiota. Recent reports have characterized the hypoxic response to various infections. However, little is known about the role of HIF activation in the context of protozoan parasitic infections...

Both the bacterial flagellum and the evolutionary related injectisome encoded on the Salmonella pathogenicity island 1 (SPI-1) play crucial roles during the infection cycle of Salmonella species. The interplay of both is highlighted by the complex cross-regulation that includes transcriptional control of the flagellar master regulatory operon flhDC by HilD, the master regulator of SPI-1 gene expression. Contrary to the HilD-dependent activation of flagellar gene expression, we report here that activation of HilD resulted in a dramatic loss of motility, which was dependent on the presence of SPI-1...

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 var gene family) for immune evasion and survival. These processes require the concerted actions of many proteins, but the molecular regulation is poorly understood. We have characterized an essential Plasmodium specific Apicomplexan AP2 (ApiAP2) transcription factor in Plasmodium falciparum (PfAP2-MRP; Master Regulator of Pathogenesis) during the intraerythrocytic developmental cycle (IDC)...

For Plasmodium falciparum, the most widespread and virulent malaria parasite that infects humans, persistence depends on continuous asexual replication in red blood cells, while transmission to their mosquito vector requires asexual blood-stage parasites to differentiate into non-replicating gametocytes. This decision is controlled by stochastic derepression of a heterochromatin-silenced locus encoding AP2-G, the master transcription factor of sexual differentiation. The frequency of ap2-g derepression was shown to be responsive to extracellular phospholipid precursors but the mechanism linking these metabolites to epigenetic regulation of ap2-g was unknown...

Eimeria tenella is an obligate intracellular parasite responsible for avian coccidiosis. Like other apicomplexan parasites, such as Toxoplasma gondii, cell invasion and intracellular development rely on apical organelle content discharge, named micronemes and rhoptries. Some rhoptry (ROP) kinases (ROPK) are key virulence factors in T. gondii. To date, among the 28 ropk genes carried by E. tenella, only two to four were confirmed by proteomic analysis or immunostaining to be expressed at the sporozoite stage...

Despite several initiatives to subside the global malaria burden, the spread of artemisinin-resistant parasites poses a big threat to malaria elimination. Mutations in PfKelch13 are predictive of ART resistance, whose underpinning molecular mechanism remains obscure. Recently, endocytosis and stress response pathways such as the ubiquitin-proteasome machinery have been linked to artemisinin resistance. With Plasmodium, however, ambiguity persists regarding a role in ART resistance for another cellular stress defence mechanism called autophagy...

Metabolism is key to cellular processes that underlie the ability of a virus to productively infect. Polyamines are small metabolites vital for many host cell processes including proliferation, transcription, and translation. Polyamine depletion also inhibits virus infection via diverse mechanisms, including inhibiting polymerase activity and viral translation. We showed that Coxsackievirus B3 (CVB3) attachment requires polyamines; however, the mechanism was unknown. Here, we report polyamines' involvement in translation, through a process called hypusination, promotes expression of cholesterol synthesis genes by supporting SREBP2 synthesis, the master transcriptional regulator of cholesterol synthesis genes...

Human papillomaviruses (HPVs) contribute to approximately 5% of all human cancers. Species-specific barriers limit the ability to study HPV pathogenesis in animal models. Murine papillomavirus (MmuPV1) provides a powerful tool to study the roles of papillomavirus genes in pathogenesis arising from a natural infection. We previously identified Protein Tyrosine Phosphatase Non-Receptor Type 14 (PTPN14), a tumor suppressor targeted by HPV E7 proteins, as a putative cellular target of MmuPV1 E7. Here, we confirmed the MmuPV1 E7-PTPN14 interaction...

The enteric nervous system (ENS), the inherent nervous system of the gastrointestinal (GI) tract is a vast nervous system that controls key GI functions, including motility. It functions at a critical interface between the gut luminal contents, including the diverse population of microorganisms deemed the microbiota, as well as the autonomic and central nervous systems. Critical development of this axis of interaction, a key determinant of human health and disease, appears to occur most significantly during early life and childhood, from the pre-natal through to the post-natal period...