Plasmodium Egress Across the Parasite Life Cycle.

Human malaria, caused by infection with Plasmodium parasites, remains one of the most important global public health problems, with the World Health Organization reporting more than 240 million cases and 600,000 deaths annually as of 2020 (World malaria report 2021). Our understanding of the biology of these parasites is critical for development of effective therapeutics and prophylactics, including both antimalarials and vaccines. Plasmodium is a protozoan organism that is intracellular for most of its life cycle. However, to complete its complex life cycle and to allow for both amplification and transmission, the parasite must egress out of the host cell in a highly regulated manner. This review discusses the major pathways and proteins involved in the egress events during the Plasmodium life cycle-merozoite and gametocyte egress out of red blood cells, sporozoite egress out of the oocyst, and merozoite egress out of the hepatocyte. The similarities, as well as the differences, between the various egress pathways of the parasite highlight both novel cell biology and potential therapeutic targets to arrest its life cycle.

Human PC4 supports telomere stability and viability in cells utilizing the alternative lengthening of telomeres mechanism.

Cancer cells with an activated Alternative Lengthening of Telomeres (ALT) mechanism elongate telomeres via homology-directed repair. Sustained telomeric replication stress is an essential trigger of ALT activity; however, it can lead to cell death if not properly restricted. By analyzing publicly available data from genome-wide CRISPR KO screenings, we have identified the multifunctional protein PC4 as a novel factor essential for ALT cell viability. Depletion of PC4 results in rapid ALT cell death, while telomerase-positive cells show minimal effects. PC4 depletion induces replication stress and telomere fragility primarily in ALT cells, and increases ALT activity. PC4 binds to telomeric DNA in cells, and its binding can be enhanced by telomeric replication stress. Finally, a mutant PC4 with partly impaired single stranded DNA binding activity is capable to localize to telomeres and suppress ALT activity and telomeric replication stress. We propose that PC4 supports ALT cell viability, at least partly, by averting telomere dysfunction. Further studies of PC4 interactions at ALT telomeres may hold promise for innovative therapies to eradicate ALT cancers.

Ultra-Fast Degradation of Mustard Gas Simulant by Titanium Dioxide-Phosphomolybdic Acid Sub-1 nm Nanobelts.

The development of novel catalysts for the rapid detoxification of sulfur mustard holds paramount importance in the field of military defense. In this work, titanium dioxide-phosphomolybdic acid sub-1 nm nanobelts (TiO2/PMA SNBs) are employed as effective catalysts for the ultra-fast degradation of mustard gas simulants (2-chloroethyl ethyl sulfide, CEES) with 100% selectivity and a half-life (t1/2, time required for 50% conversion) as short as 12 s, which is the fastest time to the best of the knowledge. Even in dark conditions, this material can still achieve over 90% conversion within 5 min. A mechanism study reveals that the rapid generation rate of 1O2 and O2 •- in the presence of TiO2/PMA SNBs and H2O2 plays a crucial role in facilitating the efficient oxidation of CEES. A filter layer of a gas mask loaded with TiO2/PMA SNBs and H2O2/polyvinylpyrrolidone cross-linked complex (PHP) is constructed, which demonstrates remarkable stability and exhibits exceptional efficacy in the detoxification of CEES in the presence of a small amount of water. This innovation offers great potential for enhancing personal protective equipment in practical applications.

Sub-Nanosheet Induced Inverse Growth of Negative Valency Au Clusters for Tumor Treatment by Enhanced Oxidative Stress.

Cluster aggregation states are thermodynamically favored at the subnanoscale, for which an inverse growth from nanoparticles to clusters may be realized on subnanometer supports. Herein, we develop Au-polyoxometalate-layered double hydroxide (Au-POM-LDH) sub-1 nm nanosheets (Sub-APL) based on the above strategy, where sub-1 nm Au clusters with negative valence are generated by the in situ disintegration of Au nanoparticles on POM-LDH supports. Sub-1 nm Au clusters with ultrahigh surface atom ratios exhibit remarkable efficiency for glutathione (GSH) depletion. The closely connected sub-1 nm Au with negative valence and POM hetero-units can promote the separation of hole-electrons, resulting in the enhanced reactive oxygen species (ROS) generation under ultrasound (US). Besides, the reversible redox of Mo in POM is able to deplete GSH and trigger chemodynamic therapy (CDT) simultaneously, further enhancing the oxidative stress. Consequently, the Sub-APL present 2-fold ROS generation under US and 7-fold GSH depletion compared to the discrete Au and POM-LDH mixture. Therefore, the serious imbalance of redox in the TME caused by the sharp increase of ROS and rapid decrease of GSH leads to death of tumor ultimately.

CdWO4 Sub-1 nm Nanowires for Visible-light CO2 Photoreduction.

Quantum size effect usually causes energy level splitting and band broadening as material size decreases. However, this may change again by the surface adsorbents, doping and defects, which rarely attracts much attention. Herein, CdWO4 sub-1 nm nanowires (SNWs) with oleylamine adsorption, PO43--doping and oxygen defects are synthesized by combining Cd(CH3COO)2, H3PW12O40 (PW12) and oleylamine (abbreviated as PO43--CdWO4-X SNWs). Compared with bulk CdWO4, they exhibit unexpected absorption spectra (extended from 292 nm to 453 nm) and bandgap (reduced from 4.25 eV to 2.74 eV), thus bringing remarkable visible-light CO2 photoreduction activity. Under 410 nm LED light irradiation, PO43--CdWO4-40 SNWs exhibit the highest photocatalytic performance with a CO2-to-CO generation rate of 1685 µmol g-1 h-1. Density functional theory (DFT) calculations demonstrate the adsorbed oleylamine raises the valence band and enhances the adsorption of reaction substrate and intermediates, thus decreasing their reduction energy barriers. Furthermore, PO43--doping and oxygen defects will generate defect energy band below the conduction band of PO43--CdWO4-40 SNWs, resulting in remarkable visible light absorption and superior photocatalytic CO2 reduction performance. This work highlights the significant impacts of surface adsorbents, doping and defects on the physicochemical and catalytic properties of sub-nano materials.

Freestanding Block Copolymer Membranes with Tunable Pore Sizes Promoted by Subnanometer Nanowires.

Block copolymers (BCPs) have enduring appeal for its intriguing assembly behaviors. Nevertheless, the unsatisfactory mechanical properties of BCPs make it a problem to fabricate freestanding membranes and hindered practical applications. Herein, a freestanding membrane with tunable pore size is prepared simply by co-assembly of BCPs and subnanometer nanowires (SNWs), combining the abundant function of BCPs and prominent mechanical properties of SNWs. Benefited from synergy of the components and the hierarchical structure, the tensile strength of composite membrane is promoted by two orders of magnitude compared to that of BCPs. With the columnar pores aligning vertically to surfaces and the pore size regulated by processing conditions, the membranes exhibit precise size-selected effect in ultrafiltration of Au nanoparticles (Au NPs) and can distinct NPs with diameter difference as tiny as 5 nm, demonstrating the promising prospect in separation technology and even widespread fields.

A microscopic scenario on recovery mechanisms under waterlogging and submergence stress in rice.

MAIN CONCLUSION: Adaptive traits in rice responding to flooding, a compound stress, are associated with morpho-anatomical and physiological changes which are regulated at the genetic level. Therefore, understanding submergence stress tolerance in rice will help development of adapted cultivars that can help mitigate agricultural losses. Rice is an important dietary component of daily human consumption and is cultivated as a staple crop worldwide. Flooding is a compound stress which imposes significant financial losses to farmers. Flood-affected rainfed rice ecosystems led to the development of various adaptive traits in different cultivars for their optimal growth and survival. Some cultivars can tolerate hypoxia by temporarily arresting elongation and conserving their energy sources, which they utilize to regrow after the stress conditions subside. However, few other cultivars rapidly elongate to escape hypoxia using carbohydrate resources. These contrasting characters are regulated at the genetic level through different quantitative trait loci that contain ERF transcription factors (TFs), Submergence and Snorkels. TFs can simultaneously activate the transcription of various genes involved in stress and development responses. These TFs are of prime importance because the introgressed and near-isogenic lines showed promising results with increased submergence tolerance without affecting yield or quality. However, the entire landscape of submergence tolerance is not entirely depicted, and further exploration in the field is necessary to understand the mechanism in rice completely. Therefore, this review will highlight the significant adaptive traits observed in flooded rice varieties and how they are regulated mechanistically.

Time-Dependent Effects of Buspirone versus Desipramine on the 5-Choice Serial Reaction Time Task in Rats Reared in Social Isolation: Implication of Early Life Experience and Motoric Impulsivity.

BACKGROUND: Early life social experience and the function of the central serotonin (5-Hydroxytryptophan, 5-HT) system are involved in development of behavioral impulsivity in which individuals act without forethought or before all necessary information is available. However, most of the evidence has been obtained from acute 5-HT manipulation, whereas, the present study aimed to investigate the effects of subchronic regimen targeting of 5-HT1A receptors on motoric waiting impulsivity in socially isolated rats. METHODS: A two-week protocol of buspirone (0.5 mg/kg/day) and desipramine (2.5 mg/kg/day) was employed for rats following social isolation rearing (IR) to examine their behavioral performance in a 5-choice serial reaction time task (5-CSRTT) during the treatment regimen. Responses in any one of the apertures prior to an informative signal were recorded as a premature response. RESULTS: IR rats presented with more locomotor activity than socially reared (SR) rats. Buspirone progressively increased the baseline level of premature responding in a time-dependent manner that was not observed in IR rats. Both IR and SR rats exhibited less premature responding following acute buspirone challenge. For a subchronic desipramine regimen, IR rats followed the same trend of SR controls to increase the prematurity of baseline response. CONCLUSIONS: Buspirone but not desipramine-induced time-dependent effects of motoric waiting impulsivity can be reversed by IR, indicating a role for early life social experience on 5-HT1A receptor-associated ability to control impulsiveness.

Transfer of Stress Resilient QTLs and Panicle Traits into the Rice Variety, Reeta through Classical and Marker-Assisted Breeding Approaches.

Reeta is a popular late-maturing high-yielding rice variety recommended for cultivation in the eastern Indian states. The cultivar is highly sensitive to submergence stress. Phosphorus deficiency is an additional constraint for realizing high yield. The quantitative trait loci (QTLs), Sub1, for submergence and Pup1 for low phosphorus stress tolerance along with narrow-grained trait, GW5 were introgressed into the variety from the donor parent, Swarna-Sub1 through marker-assisted breeding. In addition, phenotypic selections for higher panicle weight, grain number, and spikelet fertility were performed in each segregating generation. Foreground selection detected the 3 target QTLs in 9, 8 and 7 progenies in the BC1F1, BC2F1, and BC3F1 generation, respectively. Recurrent parent's genome recovery was analyzed using 168 SSR polymorphic markers. The foreground analysis in 452 BC3F2 progenies showed five pyramided lines in homozygous condition for the target QTLs. No donor fragment drag was noticed in the Sub1 and GW5 QTLs carrier while a segmentwas observed in the Pup1 carrier chromosome. The developed lines were higher yielding, had submergence, and had low phosphorus stress-tolerance alongwith similar to the recipient parent in the studied morpho-quality traits. A promising pyramided line is released in the name of Reeta-Panidhan (CR Dhan 413) for the flood-prone areas of Odisha state.

Role of Cannabinoid CB1 Receptor in Object Recognition Memory Impairment in Chronically Rapid Eye Movement Sleep-deprived Rats.

Objective We aimed to investigate whether antagonism of the cannabinoid CB1 receptor (CB1R) could affect novel object recognition (NOR) memory in chronically rapid eye movement sleep-deprived (RSD) rats.Methods The animals were examined for recognition memory following a 7-day chronic partial RSD paradigm using the multiple platform technique. The CB1R antagonist rimonabant (1 or 3 mg/kg, i.p.) was administered either at one hour prior to the sample phase for acquisition, or immediately after the sample phase for consolidation, or at one hour before the test phase for retrieval of NOR memory. For the reconsolidation task, rimonabant was administered immediately after the second sample phase.Results The RSD episode impaired acquisition, consolidation, and retrieval, but it did not affect the reconsolidation of NOR memory. Rimonabant administration did not affect acquisition, consolidation, and reconsolidation; however, it attenuated impairment of the retrieval of NOR memory induced by chronic RSD.Conclusions These findings, along with our previous report, would seem to suggest that RSD may affect different phases of recognition memory based on its duration. Importantly, it seems that the CB1R may, at least in part, be involved in the adverse effects of chronic RSD on the retrieval, but not in the acquisition, consolidation, and reconsolidation, of NOR memory.

Involvement of α1B-adrenoceptors and Rho kinase in contractions of rat aorta and mouse spleen.

α1-adrenoceptors link via the G-protein Gq/G11 to both Ca2+ entry and release from stores, but may also activate Rho kinase, which causes calcium sensitization. This study aimed to identify the subtype(s) of α1-adrenoceptor involved in Rho kinase-mediated responses in both rat aorta and mouse spleen, tissues in which contractions involve multiple subtypes of α1-adrenoceptor. Tissues were contracted with cumulative concentrations of noradrenaline (NA) in 0.5 log unit increments, before and in the presence of an antagonist or vehicle. Contractions produced by NA in rat aorta are entirely α1-adrenoceptor mediated as they are competitively blocked by prazosin. The α1A-adrenoceptor antagonist RS100329 had low potency in rat aorta. The α1D-adrenoceptor antagonist BMY7378 antagonized contractions in rat aorta in a biphasic manner: low concentrations blocking α1D-adrenoceptors and high concentrations blocking α1B-adrenoceptors. The Rho kinase inhibitor fasudil (10 µM) significantly reduced aortic contractions in terms of maximum response, suggesting inhibition of α1B-adrenoceptor mediated responses. In the mouse spleen, a tissue in which all 3 subtypes of α1-adrenoceptor are involved in contractions to NA, fasudil (3 µM) significantly reduced both early and late components to the NA contraction, the early component involving α1B- and α1D-adrenoceptors, and the late component involving α1B- and α1A-adrenoceptors. This suggests that fasudil inhibits α1B-adrenoceptor mediated responses. It is concluded that α1D- and α1B-adrenoceptors interact in rat aorta and α1D-, α1A- and α1B-adrenoceptors interact in the mouse spleen to produce contractions and these interactions suggest that one of the receptors preferentially activates Rho kinase, most likely the α1B-adrenoceptor.

Hybrid Sub-1 nm Nanosheets of Co-assembled MnZnCuOx and Polyoxometalate Clusters as Anodes for Li-ion Batteries.

Transition metal oxide (TMO) anode materials in lithium-ion batteries (LIBs) usually suffer from serious volume expansion leading to the pulverization of structures, further giving rise to lower specific capacity and worse cycling stability. Herein, by introducing polyoxometalate (POM) clusters into TMOs and precisely controlling the amount of POMs, the MnZnCuOx -phosphomolybdic acid hybrid sub-1 nm nanosheets (MZC-PMA HSNSs) anode is successfully fabricated, where the special electron rich structure of POMs is conducive to accelerating the migration of lithium ions on the anode to obtain higher specific capacity, and the non-covalent interactions between POMs and TMOs make the HSNSs possess excellent structural and chemical stability, thus exhibiting outstanding electrochemical performance in LIBs, achieving a high reversible capacity (1157 mAh g-1 at 100 mA g-1 ) and an admirable long-term cycling stability at low and high current densities.

Finding a breather for Oryza sativa: Understanding hormone signalling pathways involved in rice plants to submergence stress.

During the course of evolution, different ecotypes of rice (Oryza sativa L.) have evolved distinct strategies to cope with submergence stress. Such contrasting responses are mediated by plant hormones that are principle regulators of growth, development and responses to various biotic and abiotic stresses. These hormones act cooperatively and show extensive crosstalk which is mediated by key regulatory genes that serve as nodes of molecular communication. The presence or absence of such genes leads to significant changes in hormone signalling pathways and hence, governs the type of response that the plant will exhibit. As flooding is one of the leading causes of crop loss across all the major rice-producing countries, it is crucial to deeply understand the molecular nexus governing the response to submergence to produce flood resilient varieties. This review focuses on the hormonal signalling pathways that mediate two contrasting responses of the rice plant to submergence stress namely, rapid internode elongation to escape flood waters and quiescence response that enables the plant to survive under complete submergence. The significance of several key genes such as Sub1A-1, SLR1, SD1 and SK1/SK2, in defining the ultimate response to submergence has also been discussed.

Characterization of the Sphingolipidome of the Peri-Infarct Tissue during Hemorrhagic Transformation in a Mouse Model of Cerebral Ischemia.

BACKGROUND: Cardiovascular diseases like stroke cause changes to sphingolipid mediators like sphingosine 1-phosphate (S1P) or its ceramide analogs, which bear the potential to either alleviate or exacerbate the neurological damage. Therefore, the precise identification of alterations within the sphingolipidome during ischemic stroke (IS) and hemorrhagic transformation (HT) harbors a putative therapeutic potential to orchestrate local and systemic immunomodulatory processes. Due to the scarcity of research in this field, we aimed to characterize the sphingolipidome in IS and HT. METHODS: C57BL/6 mice underwent middle cerebral artery occlusion (MCAO) and specimens of the peri-infarct tissue were taken for sphingolipid profiling. RESULTS: Ischemic stroke resulted in reduced S1P whilst ceramides were elevated six hours post ischemia onset. However, these differences were nearly revoked at 24 hours post ischemia onset. Moreover, the topmost S1P and ceramide levels were linked to the presence of HT after MCAO. In this study we show the characterization of the sphingolipidomic landscape of the peri-infarct tissue after ischemic stroke and HT. Especially, highest values of S1P, C 18 lactosylceramide, C 18 glucosylceramide, and C 24:1 ceramide were nearly entirely expressed by mice with HT. CONCLUSIONS: Our results warrant further investigations into the immunomodulatory consequences of altered sphingolipid species for the development of HT after IS.

Circularly and Linearly Polarized Luminescence from AIE Luminogens Induced by Super-Aligned Assemblies of Sub-1†nm Nanowires.

Sub-1 nm nanowires (SNWs) combine the properties of inorganic materials and polymers. They can be highly oriented through assembly, and can also be easily processed. Meanwhile, aggregation-induced emission luminogens (AIEgens) show high potential for optical applications, but they are usually hard to process. The combination of SNWs and AIEgens can enrich both of their applications. In this study, we report that the fluorescence emission intensity of the AIEgens-SNW dispersion is dramatically enhanced due to the flexibility of SNWs. Furthermore, we fabricate two kinds of functional films with circularly polarized luminescence (CPL) and linearly polarized luminescence (LPL) activities. The construction of CPL materials didn't require any chiral chemicals. The construction of LPL materials didn't require an additional stretching process. As a result, we endowed common achiral AIEgens with a high dissymmetry factor of 0.033 and a polarization ratio of 0.44, respectively.

Au-Polyoxometalates A-B-A-B Type Copolymer-Analogue Sub-1 nm Nanowires.

Here it is shown that polyoxometalate (POM) clusters (H3 PW12 O40 ·xH2 O, PW12 ) can be introduced to interact with Au nanoclusters to form the "A-B-A-B" type building block ("A" represents Au nanoclusters and "B" stands for PW12 clusters), which continue to grow into copolymer-analogue Au-PW12 sub-1 nm nanowires. Due to the synergetic effect of Au nanoclusters and POMs, the obtained Au-PW12 sub-1 nm nanowires efficiently perform catalytic activity in the photo-electrochemical converting CO2 into CO. Under light, the catalyst maintains remarkable faradic efficiency (FE) of ≈99% from -0.7 to -0.9V (RHE), which is better than that in dark (FE of 66.4-90.64% from -0.7 to -0.9 V (RHE)). Density functional theory calculations and cryo-electron microscope images support the "A-B-A-B" type of structure and mechanistic studies also reveal the higher reactivity toward COOH* formation and CO adsorption on the catalyst, which lead to the superior catalytic activity in CO2 reduction reaction.

Recent Advances of Genetic Resources, Genes and Genetic Approaches for Flooding Tolerance in Rice.

Flooding is one of the most hazardous natural disasters and a major stress constraint to rice production throughout the world, which results in huge economic losses. The frequency and duration of flooding is predicted to increase in near future as a result of global climate change. Breeding of flooding tolerance in rice is a challenging task because of the complexity of the component traits, screening technique, environmental factors and genetic interactions. A great progress has been made during last two decades to find out the flooding tolerance mechanism in rice. An important breakthrough in submergence research was achieved by the identification of major quantitative trait locus (QTL) SUB1 in rice chromosomes that acts as the primary contributor for tolerance. This enabled the use of marker-assisted backcrossing (MABC) to transfer SUB1 QTL into popular varieties which showed yield advantages in flood prone areas. However, SUB1 varieties are not always tolerant to stagnant flooding and flooding during germination stage. So, gene pyramiding approach can be used by combining several important traits to develop new breeding rice lines that confer tolerances to different types of flooding. This review highlights the important germplasm/genetic resources of rice to different types of flooding stress. A brief discussion on the genes and genetic mechanism in rice exhibited to different types of flooding tolerance was discussed for the development of flood tolerant rice variety. Further research on developing multiple stresses tolerant rice can be achieved by combining SUB1 with other tolerance traits/genes for wider adaptation in the rain-fed rice ecosystems.

Improved Transformation and Regeneration of Indica Rice: Disruption of SUB1A as a Test Case via CRISPR-Cas9.

Gene editing by use of clustered regularly interspaced short palindromic repeats (CRISPR) has become a powerful tool for crop improvement. However, a common bottleneck in the application of this approach to grain crops, including rice (Oryza sativa), is efficient vector delivery and calli regeneration, which can be hampered by genotype-dependent requirements for plant regeneration. Here, methods for Agrobacterium-mediated and biolistic transformation and regeneration of indica rice were optimized using CRISPR-Cas9 gene-editing of the submergence tolerance regulator SUBMERGENCE 1A-1 gene of the cultivar Ciherang-Sub1. Callus induction and plantlet regeneration methods were optimized for embryogenic calli derived from immature embryos and mature seed-derived calli. Optimized regeneration (95%) and maximal editing efficiency (100%) were obtained from the immature embryo-derived calli. Phenotyping of T1 seeds derived from the edited T0 plants under submergence stress demonstrated inferior phenotype compared to their controls, which phenotypically validates the disruption of SUB1A-1 function. The methods pave the way for rapid CRISPR-Cas9 gene editing of recalcitrant indica rice cultivars.

Introgression of dual abiotic stress tolerance QTLs (Saltol QTL and Sub1 gene) into Rice (Oryza sativa L.) variety Aiswarya through marker assisted backcross breeding.

Salinity and submergence are two very prominent abiotic stress conditions affecting rice yield adversely in the coastal agro ecosystem. Marker Assisted Backcross Breeding (MABB) is an efficient and fast track molecular tool to incorporate a desired stress tolerant QTL/gene into an improved cultivar. The present study was carried out for the introgression of Saltol QTL responsible for salinity tolerance and Sub1 gene responsible for submergence tolerance into the high yielding rice variety Aiswarya independently through MABB. Final objective of the study is to develop dual stress tolerant (tolerance to salinity and submergence) Aiswarya rice variety by pyramiding the both target QTLs introgressed BC2F2 progenies having maximum background homozygosity. The donors of Saltol QTL and Sub1 gene used in the present study were FL478 and Swarna Sub1, respectively. Based on the background genome analysis of the introgressed plants, the plants with > 85-90% background similarity were selected for pyramiding of Saltol QTL and Sub1 gene into the elite background of rice variety Aiswarya. Those selected introgressed lines with Saltol QTL and Sub1 gene will be again crossed to pyramid both Saltol QTL and Sub1 gene into the rice variety Aiswarya. Such a mega rice variety pyramided with dual stress tolerant QTLs is the expected outcome of this study and can be recommended for cultivation in the flood prone saline coastal agroecosystem.

The Plasmodium berghei serine protease PbSUB1 plays an important role in male gamete egress.

The Plasmodium subtilisin-like serine protease SUB1 is expressed in hepatic and both asexual and sexual blood parasite stages. SUB1 is required for egress of invasive forms of the parasite from both erythrocytes and hepatocytes, but its subcellular localisation, function, and potential substrates in the sexual stages are unknown. Here, we have characterised the expression profile and subcellular localisation of SUB1 in Plasmodium berghei sexual stages. We show that the protease is selectively expressed in mature male gametocytes and localises to secretory organelles known to be involved in gamete egress, called male osmiophilic bodies. We have investigated PbSUB1 function in the sexual stages by generating P. berghei transgenic lines deficient in PbSUB1 expression or enzyme activity in gametocytes. Our results demonstrate that PbSUB1 plays a role in male gamete egress. We also show for the first time that the PbSUB1 substrate PbSERA3 is expressed in gametocytes and processed by PbSUB1 upon gametocyte activation. Taken together, our results strongly suggest that PbSUB1 is not only a promising drug target for asexual stages but could also be an attractive malaria transmission-blocking target.