54 research outputs found
RNA-seq analysis revealed considerable genetic diversity and enabled the development of specific KASP markers for Psathyrostachys huashanica
Psathyrostachys huashanica, which grows exclusively in Huashan, China, is an important wild relative of common wheat that has many desirable traits relevant for wheat breeding. However, the poorly characterized interspecific phylogeny and genomic variations and the relative lack of species-specific molecular markers have limited the utility of P. huashanica as a genetic resource for enhancing wheat germplasm. In this study, we sequenced the P. huashanica transcriptome, resulting in 50,337,570 clean reads that were assembled into 65,617 unigenes, of which 38,428 (58.56%) matched at least one sequence in public databases. The phylogenetic analysis of P. huashanica, Triticeae species, and Poaceae species was conducted using 68 putative orthologous gene clusters. The data revealed the distant evolutionary relationship between P. huashanica and common wheat as well as the substantial diversity between the P. huashanica genome and the wheat D genome. By comparing the transcriptomes of P. huashanica and Chinese Spring, 750,759 candidate SNPs between P. huashanica Ns genes and their common wheat orthologs were identified. Among the 90 SNPs in the exon regions with different functional annotations, 58 (64.4%) were validated as Ns genome-specific SNPs in the common wheat background by KASP genotyping assays. Marker validation analyses indicated that six specific markers can discriminate between P. huashanica and the other wheat-related species. In addition, five markers are unique to P. huashanica, P. juncea, and Leymus species, which carry the Ns genome. The Ns genome-specific markers in a wheat background were also validated regarding their specificity and stability for detecting P. huashanica chromosomes in four wheatāP. huashanica addition lines. Four and eight SNP markers were detected in wheatāP. huashanica 2Ns and 7Ns addition lines, respectively, and one marker was specific to both wheatāP. huashanica 3Ns, 4Ns, and 7Ns addition lines. These markers developed using transcriptome data may be used to elucidate the genetic relationships among Psathyrostachys, Leymus, and other closely-related species. They may also facilitate precise introgressions and the high-throughput monitoring of P. huashanica exogenous chromosomes or segments in future crop breeding programs
Bisphosphoglycerate mutase deficiency protects against cerebral malaria and severe malaria-induced anemia
The replication cycle and pathogenesis of the Plasmodium malarial parasite involves rapid expansion in red blood cells (RBCs), and variants of certain RBC-specific proteins protect against malaria in humans. In RBCs, bisphosphoglycerate mutase (BPGM) acts as a key allosteric regulator of hemoglobin/oxyhemoglobin. We demonstrate here that a loss-of-function mutation in the murine Bpgm (BpgmL166P) gene confers protection against both Plasmodium-induced cerebral malaria and blood-stage malaria. The malaria protection seen in BpgmL166P mutant mice is associated with reduced blood parasitemia levels, milder clinical symptoms, and increased survival. The protective effect of BpgmL166P involves a dual mechanism that enhances the hostās stress erythroid response to Plasmodium-driven RBC loss and simultaneously alters the intracellular milieu of the RBCs, including increased oxyhemoglobin and reduced energy metabolism, reducing Plasmodium maturation, and replication. Overall, our study highlights the importance of BPGM as a regulator of hemoglobin/oxyhemoglobin in malaria pathogenesis and suggests a new potential malaria therapeutic target
A G358S mutation in the Plasmodium falciparum Na<sup>+</sup> pump PfATP4 confers clinically-relevant resistance to cipargamin
Diverse compounds target the Plasmodium falciparum Na(+) pump PfATP4, with cipargamin and (+)-SJ733 the most clinically-advanced. In a recent clinical trial for cipargamin, recrudescent parasites emerged, with most having a G358S mutation in PfATP4. Here, we show that PfATP4(G358S) parasites can withstand micromolar concentrations of cipargamin and (+)-SJ733, while remaining susceptible to antimalarials that do not target PfATP4. The G358S mutation in PfATP4, and the equivalent mutation in Toxoplasma gondii ATP4, decrease the sensitivity of ATP4 to inhibition by cipargamin and (+)-SJ733, thereby protecting parasites from disruption of Na(+) regulation. The G358S mutation reduces the affinity of PfATP4 for Na(+) and is associated with an increase in the parasiteās resting cytosolic [Na(+)]. However, no defect in parasite growth or transmissibility is observed. Our findings suggest that PfATP4 inhibitors in clinical development should be tested against PfATP4(G358S) parasites, and that their combination with unrelated antimalarials may mitigate against resistance development
L166P mutation in bisphosphoglycerate mutase confers resistance to Malaria
Malaria is a parasitic disease that continues to be a major driver of poverty in endemic areas, despite progress in its control and eradication. Malaria has affected humans for many millennia and as a result, has exerted a strong evolutionary selection on the human genome. Due to genetic and epidemiological studies, various polymorphisms and mutations have been found to innately protect against us against Plasmodium infections. Murine models of malaria have been used extensively to study host-response to malaria as there are significant genomic conservation between mice and humans. The study presented herein discuss the characterization of a novel N-ethyl-N-nitrosourea (ENU) induced mutation at position 166 in murine Bisphosphoglycerate mutase (BPGM).The pathogenesis of malaria is directly associated with the intra-erythrocytic lifecycle of the Plasmodium parasite. As BPGM is an erythrocyte specific protein, it is of valuable interest to investigate the relationship between BPGM and malaria infections. Ultimately, this thesis will address the malaria protective role of BPGM deficiency through the use of murine models of malaria. To do this, the functional consequences of the ENU-induced mutation in Bpgm was first elucidated, along with its effect on erythropoiesis and erythrocytes. We demonstrated that amino acid substitution of leucine at position 166 had detrimental effect on BPGM protein stability, which consequently lead to a polycythemia-like phenotype at steady state in mutant mice.A critical highlight of the study was the discovery that our ENU-induced mutation in Bpgm conferred protection to experimental cerebral malaria induced by Plasmodium berghei ANKA and to severe malarial anemia caused by Plasmodium chabaudi AS. Subsequently, we investigated the erythropoietic response of BPGM mutant mice under conditions of Plasmodium induced- stress and demonstrated that mutant mice are capable of producing a more effective erythropoietic response. Lastly, we found that Bpgm deficiency conferred resistance to malaria through a dual mechanism, as we also found that Plasmodium parasite have an impairment in their replicative capacity in mutant erythrocytes. Overall, our work presents a novel mutation in BPGM and shows the importance of the protein in malaria infection.Le paludisme, communeĢment appeleĢ malaria, est une maladie parasitaire qui contribue en grande partie aĢ la pauvreteĢ des reĢgions ouĢ lāinfection est toujours endeĢmique, et ce, malgreĢ de nombreux progreĢs effectueĢs en vue dāun meilleur controĢle et dāune eĢradication compleĢte de la maladie. PreĢsent depuis des sieĢcles, le paludisme a exerceĢ une forte pression seĢlective sur lāeĢvolution du geĢnome humain. Ainsi, de reĢcentes eĢtudes geĢneĢtiques et eĢpideĢmiologiques ont permis lāidentification de plusieurs mutations et variantes polymorphiques qui nous confeĢrent une protection inneĢe contre les infections au genre Plasmodium. Notamment, lāutilisation de modeĢles murins, compte tenu le haut niveau de conservation geĢneĢtique entre lāhomme et la souris, a beaucoup servi aĢ lāeĢtude de la reĢponse de l'hoĢte au paludisme. La preĢsente eĢtude porte sur la caracteĢrisation dāune nouvelle mutation induite chez la souris par le mutageĢne N-ethyl-N- nitrosourea (ENU), au niveau de lāacide amineĢ en position 166 de la proteĢine Bisphosphoglycerate mutase (BPGM).La pathogeneĢse de la malaria est directement associeĢe au cycle de vie intraeĢrythrocytaire du parasite Plasmodium. BPGM eĢtant une proteĢine retrouveĢe uniquement chez les cellules eĢrythrocytes, il est dāun inteĢreĢt preĢcieux dāeĢtudier la relation entre BPGM et les infections paludeĢennes. Par conseĢquent, cette theĢse abordera le meĢcanisme par lequel une deĢficience en BPGM assure une meilleure protection face au paludisme, aĢ lāaide de modeĢles murins dāinfection. AĢ cette fin, les conseĢquences fonctionnelles de cette mutation introduite via ENU dans la proteĢine BPGM ont d'abord eĢteĢ eĢlucideĢes, ainsi que leurs effets sur l'eĢrythropoiĢeĢse et sur les eĢrythrocytes. Nous avons deĢmontreĢ que la substitution de lāacide amineĢ leucine aĢ la position 166 avait un effet deĢleĢteĢre sur la stabiliteĢ de la proteĢine BPGM, responsable dāun pheĢnotype qui sāapparentait aĢ la polycytheĢmie chez les souris aĢ lāeĢtat neutre.Lāun des points importants de cette eĢtude a eĢteĢ la deĢcouverte que notre mutation ENU confeĢrait une protection aĢ deux modeĢles distincts dāinfection au Plasmodium, soit au paludisme ceĢreĢbral induit expeĢrimentalement par Plasmodium berghei ANKA et aĢ lāaneĢmie seĢveĢre causeĢe par Plasmodium chabaudi AS. Ensuite, nous avons eĢvalueĢ les fonctions eĢrythropoiĢeĢtiques des souris mutantes BPGM en reĢponse aux conditions de stress provoqueĢes par le parasite Plasmodium, et avons ainsi deĢmontreĢ que les souris mutantes sont capable dāinduire une reĢponse eĢrythropoiĢeĢtique beaucoup plus efficace quāaĢ la normale. Enfin, nous avons constateĢ que la deĢficience en BPGM accordait une reĢsistance au paludisme par un double meĢcanisme, le second eĢtant la capaciteĢ des eĢrythrocytes mutants aĢ empeĢcher la reĢplication des parasites Plasmodium. Dans lāensemble, notre eĢtude deĢcrit une nouvelle mutation de la proteĢine BPGM et deĢmontre lāimportance de cet enzyme dans lāinfection malaria
Experimental research on wear mechanism of diamond wheels for grinding Cf/SiC composites grooves
Aiming at the problems of low processing efficiency, low groove shape accuracy and poor surface quality caused by grinding wheel wear in the grinding process of Cf/SiC composite grooves. In this paper, based on the motion mode of grinding wheel grinding, the wear volume formula of grinding wheels was analyzed, and the grinding wheel wear comparison experiment of different bond diamond grinding wheels grinding Cf/SiC composite grooves was carried out, and the more suitable kind of diamond grinding wheel for grinding Cf/SiC composite grooves was selected. From the experimental results, compared with the ceramic-bonded diamond wheel and resin-bonded diamond wheel, the grinding times of electroplated diamond wheel grinding Cf/SiC composites were increased by 20 and 104, respectively, and the surface roughness of the groove was most stable and the processing damage was smallest. Therefore, the best quality of grinding Cf/SiC composites groove was obtained by the electroplated diamond grinding wheel, and its life in grinding Cf/SiC composites was the longest. At the same time, the wear mechanism of the electroplated grinding wheel was explored, the wear on the bottom surface of the electroplated grinding wheel was more serious than that on the circumferential surface. The wear on the bottom surface was mainly wear and tear, and it gradually diffused along the inner diameter of the grinding wheel with the increasing grinding times
The low infrared emissivity of Ce1-xYxO2-x/2 samples at high-temperature contributed by enhanced conductivity
The Ce1-xYxO2-x/2 samples were synthesized with different doping amount by solid state reaction method. Phase structures of the samples were analyzed and characterized by XRD. The effects of different doping amount on infrared emissivity properties at 3-5Āµm wavebands were investigated systematically. It is found that the powder with doping molality of x=0.2 exhibits the lowest infrared emissivity value ca. 0.21 when the test temperature is 600 Ā°C. The mechanism for the low infrared emissivity is explored thoroughly. The reduction of infrared emissivity with increasing temperature is ascribed to the enhancement of electrical conductivity. Our results suggest that Ce1-xYxO2-x/2 powder with x=0.2 is a potential candidate for stealth material of aircraft engines
The low infrared emissivity of Ce
The Ce1-xYxO2-x/2 samples were synthesized with different doping amount by solid state reaction method. Phase structures of the samples were analyzed and characterized by XRD. The effects of different doping amount on infrared emissivity properties at 3-5Āµm wavebands were investigated systematically. It is found that the powder with doping molality of x=0.2 exhibits the lowest infrared emissivity value ca. 0.21 when the test temperature is 600 Ā°C. The mechanism for the low infrared emissivity is explored thoroughly. The reduction of infrared emissivity with increasing temperature is ascribed to the enhancement of electrical conductivity. Our results suggest that Ce1-xYxO2-x/2 powder with x=0.2 is a potential candidate for stealth material of aircraft engines
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