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 wheat–P. huashanica addition lines. Four and eight SNP markers were detected in wheat–P. huashanica 2Ns and 7Ns addition lines, respectively, and one marker was specific to both wheat–P. 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 host’s 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⁺ 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 parasite’s 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, communément appelé malaria, est une maladie parasitaire qui contribue en grande partie à la pauvreté des régions où l’infection est toujours endémique, et ce, malgré de nombreux progrès effectués en vue d’un meilleur contrôle et d’une éradication complète de la maladie. Présent depuis des siècles, le paludisme a exercé une forte pression sélective sur l’évolution du génome humain. Ainsi, de récentes études génétiques et épidémiologiques ont permis l’identification de plusieurs mutations et variantes polymorphiques qui nous confèrent une protection innée contre les infections au genre Plasmodium. Notamment, l’utilisation de modèles murins, compte tenu le haut niveau de conservation génétique entre l’homme et la souris, a beaucoup servi à l’étude de la réponse de l'hôte au paludisme. La présente étude porte sur la caractérisation d’une nouvelle mutation induite chez la souris par le mutagène N-ethyl-N- nitrosourea (ENU), au niveau de l’acide aminé en position 166 de la protéine Bisphosphoglycerate mutase (BPGM).La pathogenèse de la malaria est directement associée au cycle de vie intraérythrocytaire du parasite Plasmodium. BPGM étant une protéine retrouvée uniquement chez les cellules érythrocytes, il est d’un intérêt précieux d’étudier la relation entre BPGM et les infections paludéennes. Par conséquent, cette thèse abordera le mécanisme par lequel une déficience en BPGM assure une meilleure protection face au paludisme, à l’aide de modèles murins d’infection. À cette fin, les conséquences fonctionnelles de cette mutation introduite via ENU dans la protéine BPGM ont d'abord été élucidées, ainsi que leurs effets sur l'érythropoïèse et sur les érythrocytes. Nous avons démontré que la substitution de l’acide aminé leucine à la position 166 avait un effet délétère sur la stabilité de la protéine BPGM, responsable d’un phénotype qui s’apparentait à la polycythémie chez les souris à l’état neutre.L’un des points importants de cette étude a été la découverte que notre mutation ENU conférait une protection à deux modèles distincts d’infection au Plasmodium, soit au paludisme cérébral induit expérimentalement par Plasmodium berghei ANKA et à l’anémie sévère causée par Plasmodium chabaudi AS. Ensuite, nous avons évalué les fonctions érythropoïétiques des souris mutantes BPGM en réponse aux conditions de stress provoquées par le parasite Plasmodium, et avons ainsi démontré que les souris mutantes sont capable d’induire une réponse érythropoïétique beaucoup plus efficace qu’à la normale. Enfin, nous avons constaté que la déficience en BPGM accordait une résistance au paludisme par un double mécanisme, le second étant la capacité des érythrocytes mutants à empêcher la réplication des parasites Plasmodium. Dans l’ensemble, notre étude décrit une nouvelle mutation de la protéine BPGM et démontre l’importance de cet enzyme dans l’infection 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 3-5µm 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 °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 3-5µm 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 °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