scholarly journals Role of a patatin-like phospholipase in Plasmodium falciparum gametogenesis and malaria transmission

2019 ◽  
Vol 116 (35) ◽  
pp. 17498-17508 ◽  
Author(s):  
Pallavi Singh ◽  
Aditi Alaganan ◽  
Kunal R. More ◽  
Audrey Lorthiois ◽  
Sabine Thiberge ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Membrane Remodeling ◽  
Gene Encoding ◽  
Conditional Deletion ◽  
Male Gametes ◽  
Complex Process ◽  
Intracellular Vesicles ◽  
Vesicle Secretion

Transmission of Plasmodium falciparum involves a complex process that starts with the ingestion of gametocytes by female Anopheles mosquitoes during a blood meal. Activation of gametocytes in the mosquito midgut triggers “rounding up” followed by egress of both male and female gametes. Egress requires secretion of a perforin-like protein, PfPLP2, from intracellular vesicles to the periphery, which leads to destabilization of peripheral membranes. Male gametes also develop flagella, which assist in binding female gametes for fertilization. This process of gametogenesis, which is key to malaria transmission, involves extensive membrane remodeling as well as vesicular discharge. Phospholipase A2 enzymes (PLA2) are known to mediate membrane remodeling and vesicle secretion in diverse organisms. Here, we show that a P. falciparum patatin-like phospholipase (PfPATPL1) with PLA2 activity plays a key role in gametogenesis. Conditional deletion of the gene encoding PfPATPL1 does not affect P. falciparum blood stage growth or gametocyte development but reduces efficiency of rounding up, egress, and exflagellation of gametocytes following activation. Interestingly, deletion of the PfPATPL1 gene inhibits secretion of PfPLP2, reducing the efficiency of gamete egress. Deletion of PfPATPL1 also reduces the efficiency of oocyst formation in mosquitoes. These studies demonstrate that PfPATPL1 plays a role in gametogenesis, thereby identifying PLA2 phospholipases such as PfPATPL1 as potential targets for the development of drugs to block malaria transmission.

scholarly journals A patatin-like phospholipase is crucial for gametocyte induction in the malaria parasite Plasmodium falciparum

2019 ◽  
Author(s):  
Ansgar Flammersfeld ◽  
Atscharah Panyot ◽  
Yoshiki Yamaryo ◽  
Philipp Auraß ◽  
Jude M. Pryborski ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Parasite ◽  
Blood Stage ◽  
Gene Encoding ◽  
Asexual Blood Stage ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Eukaryotic Organisms ◽  
Phospholipid Degradation

AbstractPatatin-like phospholipases (PNPLAs) are highly conserved enzymes of prokaryotic and eukaryotic organisms with major roles in lipid homeostasis. The genome of the malaria parasite Plasmodium falciparum encodes four putative PNPLAs with predicted functions during phospholipid degradation. We here investigated the role of one of the plasmodial PNPLAs, a putative PLA2 termed PNPLA1, during blood stage replication and gametocyte development. PNPLA1 is present in the asexual and sexual blood stages and here localizes to the cytoplasm. PNPLA1-deficiency due to gene disruption or conditional gene-knockdown had no effect on erythrocytic replication, gametocyte maturation and gametogenesis. However, blood stage parasites lacking PNPLA1 were severely impaired in gametocyte induction, while PNPLA1 overexpression promotes gametocyte formation. The loss of PNPLA1 further leads to transcriptional down-regulation of genes related to gametocytogenesis, including the gene encoding the sexual commitment regulator AP2-G. Additionally, lipidomics of PNPLA1-deficient asexual blood stage parasites revealed overall increased levels of major phospholipids, including phosphatidylcholine (PC), which is a substrate of PLA2. Because PC synthesis is pivotal for erythrocytic replication, while the reduced availability of PC precursors drives the parasite into gametocytogenesis, we hypothesize that the high PC levels due to PNPLA1-deficiency prevent the blood stage parasites from entering the sexual pathway.

scholarly journals Dynamics and role of antibodies to Plasmodium falciparum merozoite antigens in children living in two settings with differing malaria transmission intensity

Vaccine ◽  
2016 ◽  
Vol 34 (1) ◽  
pp. 160-166 ◽  
Author(s):  
David Tiga Kangoye ◽  
Victorine Atanase Mensah ◽  
Linda Muthoni Murungi ◽  
Irene Nkumama ◽  
Issa Nebie ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Transmission Intensity ◽  
Malaria Transmission Intensity ◽  
Falciparum Merozoite ◽  
Merozoite Antigens

scholarly journals Dynamical malaria models reveal how immunity buffers effect of climate variability

2015 ◽  
Vol 112 (28) ◽  
pp. 8786-8791 ◽  
Author(s):  
Karina Laneri ◽  
Richard E. Paul ◽  
Adama Tall ◽  
Joseph Faye ◽  
Fatoumata Diene-Sarr ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Immune Responses ◽  
Malaria Transmission ◽  
Entomological Inoculation Rate ◽  
Meteorological Conditions ◽  
Climatic Forcing ◽  
Immunological Mechanisms ◽  
Short And Long Term

Assessing the influence of climate on the incidence of Plasmodium falciparum malaria worldwide and how it might impact local malaria dynamics is complex and extrapolation to other settings or future times is controversial. This is especially true in the light of the particularities of the short- and long-term immune responses to infection. In sites of epidemic malaria transmission, it is widely accepted that climate plays an important role in driving malaria outbreaks. However, little is known about the role of climate in endemic settings where clinical immunity develops early in life. To disentangle these differences among high- and low-transmission settings we applied a dynamical model to two unique adjacent cohorts of mesoendemic seasonal and holoendemic perennial malaria transmission in Senegal followed for two decades, recording daily P. falciparum cases. As both cohorts are subject to similar meteorological conditions, we were able to analyze the relevance of different immunological mechanisms compared with climatic forcing in malaria transmission. Transmission was first modeled by using similarly unique datasets of entomological inoculation rate. A stochastic nonlinear human–mosquito model that includes rainfall and temperature covariates, drug treatment periods, and population variability is capable of simulating the complete dynamics of reported malaria cases for both villages. We found that under moderate transmission intensity climate is crucial; however, under high endemicity the development of clinical immunity buffers any effect of climate. Our models open the possibility of forecasting malaria from climate in endemic regions but only after accounting for the interaction between climate and immunity.

Social Cohesion, Breaks, and Transformations in Italy, 535–600

2018 ◽  
Author(s):  
Walter Pohl
Keyword(s):  
The Political ◽  
Late Antique ◽  
Religious Context ◽  
Ancient Society ◽  
Complex Process ◽  
Term Change ◽  
Two Generations ◽  
Classical Culture

When the Gothic War began in Italy in 535, the country still conserved many features of classical culture and late antique administration. Much of that was lost in the political upheavals of the following decades. Building on Chris Wickham’s work, this contribution sketches an integrated perspective of these changes, attempting to relate the contingency of events to the logic of long-term change, discussing political options in relation to military and economic means, and asking in what ways the erosion of consensus may be understood in a cultural and religious context. What was the role of military entrepreneurs of more or less barbarian or Roman extraction in the distribution or destruction of resources? How did Christianity contribute to the transformation of ancient society? The old model of barbarian invasions can contribute little to understanding this complex process. It is remarkable that for two generations, all political strategies in Italy ultimately failed.

scholarly journals Effect of seasonal malaria chemoprevention plus azithromycin on Plasmodium falciparum transmission: gametocyte infectivity and mosquito fitness

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Koudraogo Bienvenue Yaméogo ◽  
Rakiswendé Serge Yerbanga ◽  
Seydou Bienvenu Ouattara ◽  
Franck A. Yao ◽  
Thierry Lefèvre ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Life History Traits ◽  
Controlled Trial ◽  
Double Blind ◽  
Membrane Feeding ◽  
Seasonal Malaria Chemoprevention ◽  
Negative Effect ◽  
Transmission Period ◽  
Membrane Feeding Assay

Abstract Background Seasonal malaria chemoprevention (SMC) consists of administration of sulfadoxine-pyrimethamine (SP) + amodiaquine (AQ) at monthly intervals to children during the malaria transmission period. Whether the addition of azithromycin (AZ) to SMC could potentiate the benefit of the intervention was tested through a double-blind, randomized, placebo-controlled trial. The effect of SMC and the addition of AZ, on malaria transmission and on the life history traits of Anopheles gambiae mosquitoes have been investigated. Methods The study included 438 children randomly selected from among participants in the SMC + AZ trial and 198 children from the same area who did not receive chemoprevention. For each participant in the SMC + AZ trial, blood was collected 14 to 21 days post treatment, examined for the presence of malaria sexual and asexual stages and provided as a blood meal to An. gambiae females using a direct membrane-feeding assay. Results The SMC treatment, with or without AZ, significantly reduced the prevalence of asexual Plasmodium falciparum (LRT X22 = 69, P < 0.0001) and the gametocyte prevalence (LRT X22 = 54, P < 0.0001). In addition, the proportion of infectious feeds (LRT X22 = 61, P < 0.0001) and the prevalence of oocysts among exposed mosquitoes (LRT X22 = 22.8, P < 0.001) was reduced when mosquitoes were fed on blood from treated children compared to untreated controls. The addition of AZ to SPAQ was associated with an increased proportion of infectious feeds (LRT X21 = 5.2, P = 0.02), suggesting a significant effect of AZ on gametocyte infectivity. There was a slight negative effect of SPAQ and SPAQ + AZ on mosquito survival compared to mosquitoes fed with blood from control children (LRTX22 = 330, P < 0.0001). Conclusion This study demonstrates that SMC may contribute to a reduction in human to mosquito transmission of P. falciparum, and the reduced mosquito longevity observed for females fed on treated blood may increase the benefit of this intervention in control of malaria. The addition of AZ to SPAQ in SMC appeared to enhance the infectivity of gametocytes providing further evidence that this combination is not an appropriate intervention.

scholarly journals AP2M1 Supports TGF-β Signals to Promote Collagen Expression by Inhibiting Caveolin Expression

2021 ◽  
Vol 22 (4) ◽  
pp. 1639
Author(s):  
Saerom Lee ◽  
Ga-Eun Lim ◽  
Yong-Nyun Kim ◽  
Hyeon-Sook Koo ◽  
Jaegal Shim
Keyword(s):  
Rna Seq ◽  
Gene Encoding ◽  
Caveolin 1 ◽  
Collagen Expression ◽  
Disease States ◽  
Tumor Growth Factor ◽  
Complex Process ◽  
Collagen Protein ◽  
Complex Regulation ◽  
Collagen Genes

The extracellular matrix (ECM) is important for normal development and disease states, including inflammation and fibrosis. To understand the complex regulation of ECM, we performed a suppressor screening using Caenorhabditis elegans expressing the mutant ROL-6 collagen protein. One cuticle mutant has a mutation in dpy-23 that encodes the μ2 adaptin (AP2M1) of clathrin-associated protein complex II (AP-2). The subsequent suppressor screening for dpy-23 revealed the lon-2 mutation. LON-2 functions to regulate body size through negative regulation of the tumor growth factor-beta (TGF-β) signaling pathway responsible for ECM production. RNA-seq analysis showed a dominant change in the expression of collagen genes and cuticle components. We noted an increase in the cav-1 gene encoding caveolin-1, which functions in clathrin-independent endocytosis. By knockdown of cav-1, the reduced TGF-β signal was significantly restored in the dpy-23 mutant. In conclusion, the dpy-23 mutation upregulated cav-1 expression in the hypodermis, and increased CAV-1 resulted in a decrease of TβRI. Finally, the reduction of collagen expression including rol-6 by the reduced TGF-β signal influenced the cuticle formation of the dpy-23 mutant. These findings could help us to understand the complex process of ECM regulation in organism development and disease conditions.

scholarly journals An increasing role of pyrethroid-resistant Anopheles funestus in malaria transmission in the Lake Zone, Tanzania

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nancy S. Matowo ◽  
Jackline Martin ◽  
Manisha A. Kulkarni ◽  
Jacklin F. Mosha ◽  
Eliud Lukole ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Anopheles Funestus ◽  
Sub Saharan Africa ◽  
North West ◽  
Vector Population ◽  
Lake Zone ◽  
Sub Saharan ◽  
Long Lasting Insecticidal Nets ◽  
Study District

AbstractAnopheles funestus is playing an increasing role in malaria transmission in parts of sub-Saharan Africa, where An. gambiae s.s. has been effectively controlled by long-lasting insecticidal nets. We investigated vector population bionomics, insecticide resistance and malaria transmission dynamics in 86 study clusters in North-West Tanzania. An. funestus s.l. represented 94.5% (4740/5016) of all vectors and was responsible for the majority of malaria transmission (96.5%), with a sporozoite rate of 3.4% and average monthly entomological inoculation rate (EIR) of 4.57 per house. Micro-geographical heterogeneity in species composition, abundance and transmission was observed across the study district in relation to key ecological differences between northern and southern clusters, with significantly higher densities, proportions and EIR of An. funestus s.l. collected from the South. An. gambiae s.l. (5.5%) density, principally An. arabiensis (81.1%) and An. gambiae s.s. (18.9%), was much lower and closely correlated with seasonal rainfall. Both An. funestus s.l. and An. gambiae s.l. were similarly resistant to alpha-cypermethrin and permethrin. Overexpression of CYP9K1, CYP6P3, CYP6P4 and CYP6M2 and high L1014S-kdr mutation frequency were detected in An. gambiae s.s. populations. Study findings highlight the urgent need for novel vector control tools to tackle persistent malaria transmission in the Lake Region of Tanzania.

scholarly journals The Role of Mitochondria in Carcinogenesis

2021 ◽  
Vol 22 (10) ◽  
pp. 5100
Author(s):  
Paulina Kozakiewicz ◽  
Ludmiła Grzybowska-Szatkowska ◽  
Marzanna Ciesielka ◽  
Jolanta Rzymowska
Keyword(s):  
Prostate Cancer ◽  
Mitochondrial Dna ◽  
Nuclear Dna ◽  
Dna Polymorphisms ◽  
Gene Encoding ◽  
Dna Mutations ◽  
Nadh Ubiquinone Oxidoreductase ◽  
Gene Coi ◽  
The Impact

The mitochondria are essential for normal cell functioning. Changes in mitochondrial DNA (mtDNA) may affect the occurrence of some chronic diseases and cancer. This process is complex and not entirely understood. The assignment to a particular mitochondrial haplogroup may be a factor that either contributes to cancer development or reduces its likelihood. Mutations in mtDNA occurring via an increase in reactive oxygen species may favour the occurrence of further changes both in mitochondrial and nuclear DNA. Mitochondrial DNA mutations in postmitotic cells are not inherited, but may play a role both in initiation and progression of cancer. One of the first discovered polymorphisms associated with cancer was in the gene NADH-ubiquinone oxidoreductase chain 3 (mt-ND3) and it was typical of haplogroup N. In prostate cancer, these mutations and polymorphisms involve a gene encoding subunit I of respiratory complex IV cytochrome c oxidase subunit 1 gene (COI). At present, a growing number of studies also address the impact of mtDNA polymorphisms on prognosis in cancer patients. Some of the mitochondrial DNA polymorphisms occur in both chronic disease and cancer, for instance polymorphism G5913A characteristic of prostate cancer and hypertension.

scholarly journals Controlled Transcription of Regulator Gene carS by Tet-on or by a Strong Promoter Confirms Its Role as a Repressor of Carotenoid Biosynthesis in Fusarium fujikuroi

2020 ◽  
Vol 9 (1) ◽  
pp. 71
Author(s):  
Julia Marente ◽  
Javier Avalos ◽  
M. Carmen Limón
Keyword(s):  
Wild Strain ◽  
Ring Finger ◽  
Carotenoid Biosynthesis ◽  
Negative Regulator ◽  
Fusarium Fujikuroi ◽  
Structural Genes ◽  
Gene Encoding ◽  
In The Wild ◽  
Set Up

Carotenoid biosynthesis is a frequent trait in fungi. In the ascomycete Fusarium fujikuroi, the synthesis of the carboxylic xanthophyll neurosporaxanthin (NX) is stimulated by light. However, the mutants of the carS gene, encoding a protein of the RING finger family, accumulate large NX amounts regardless of illumination, indicating the role of CarS as a negative regulator. To confirm CarS function, we used the Tet-on system to control carS expression in this fungus. The system was first set up with a reporter mluc gene, which showed a positive correlation between the inducer doxycycline and luminescence. Once the system was improved, the carS gene was expressed using Tet-on in the wild strain and in a carS mutant. In both cases, increased carS transcription provoked a downregulation of the structural genes of the pathway and albino phenotypes even under light. Similarly, when the carS gene was constitutively overexpressed under the control of a gpdA promoter, total downregulation of the NX pathway was observed. The results confirmed the role of CarS as a repressor of carotenogenesis in F. fujikuroi and revealed that its expression must be regulated in the wild strain to allow appropriate NX biosynthesis in response to illumination.

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