Gene introgression in assessing fitness costs associated with phosphine resistance in the rusty grain beetle

The current study investigates the fitness cost associated with phosphine resistance in the rusty grain beetle, Cryptolestes ferrugineus (Stephens), a problematic pest in the stored commodities that has developed strong resistance to fumigant phosphine. Three characterised insect strains: the susceptible (Ref-S), the strongly resistant (Ref-R), the introgressed resistant (Intro-R) and a segregating population (F25) derived from crossing the Ref-S and Ref-R strains were used in this study. Intro-R was developed by introgressing two phosphine resistance genes, cf_rph1 and cf_rph2 into Ref-S, aimed to reduce the influence of background genetic factors. Intro-R exhibited 592 × resistance to phosphine and homozygous for strong resistance allele, cf_rph2 (L73N). Two key fitness cost criteria, developmental time and fecundity, were assessed under optimal and suboptimal conditions (less favourable diet and low temperature). There was no significant difference in developmental time and fecundity between Ref-S and either Intro-R strain or F25 under optimal conditions. When challenged with a less favourable diet, cracked wheat + cracked sorghum (CW + CS), or exposed to a low temperature (22 °C), both Intro-R and Ref-S had similar developmental time and total numbers of F1 progeny, confirming the absence of significant fitness effects expressed in these conditions. Therefore, we conclude that strongly phosphine resistant C. ferrugineus are unlikely to incur potential fitness costs. This finding will have implications towards developing strategies to manage this pest

4-(4-Bromo­phen­yl)-6-(1H-indol-3-yl)-2,2′-bipyridine-5-carbonitrile

In the title compound, C25H15BrN4, the two pyridine rings lie in a common plane [r.m.s. deviation = 0.023 (2) Å], whereas the bromo­phenyl and indole rings are twisted away from this plane by 52.82 (12) and 28.02 (10)°, respectively. The crystal structure is stabilized by inter­molecular N—H⋯N inter­actions

4-(2,4-Dichlorophenyl)-2-(1H-indol-3-yl)-6-methoxypyridine-3,5-dicarbonitrile

In the title compound, C22H12Cl2N4O, the indole ring system and the benzene ring form dihedral angles of 21.18 (7)° and 68.43 (8)°, respectively, with the pyridine ring. The meth­oxy group is coplanar with the pyridine ring. In the crystal structure N—H⋯N inter­molecular hydrogen bonds link the mol­ecules into C(10) chains running along [011]. Intramolec­ular C—H⋯N hydrogen bonds are also observed

Trimethyl 1-(2-methyl-1-phenylsulfonyl-1H-indol-3-yl)propane-1,2,3-tricarbox­ylate

In the title compound, C24H25NO8S, the indole unit is planar and makes a dihedral angle of 79.73 (11)° with the phenyl ring of the sulfonyl substituent. The mol­ecules in the unit cell are stabilized by C—H⋯O and C—H⋯π inter­molecular inter­actions in addition to van der Waals forces

Diethyl 2-oxo-3-(2-oxo-2,3-dihydro-1H-indol-3-yl­idene)butane­dioate

The title compound, C16H15NO6, crystallizes with two symmetry–independent mol­ecules in the asymmetric unit. The crystal structure is stabilized by inter­molecular C—H⋯O and N—H⋯O hydrogen bonds, and intra­molecular C—H⋯O hydrogen bonds. In addition, the crystal structure exhibits two inter­molecular C—H⋯π inter­actions

4-(2,4-Dichlorophenyl)-2-(1H-indol-3-yl)-6-(2-pyridyl)-1,4-dihydropyridine-4-carbonitrile

The title compound, C25H16Cl2N4, has intra­molecular N—H⋯N and C—H⋯Cl hydrogen bonds. In the crystal structure, mol­ecules are linked through N—H⋯N hydrogen bonds, forming a centrosymmetric R 2 2(16) dimer

3′-Benz­yloxy-3-hydr­oxy-3,3′-bi-1H-indole-2,2′(3H,3′H)-dione monohydrate

In the title compound, C23H18N2O4·H2O, the two oxindole rings subtend a dihedral angle of 54.29 (5)°. The crystal structure is stabilized by intermolecular N—H⋯O, O—H⋯O and C—H⋯π inter­actions

1′-Methyl-2,2′′-dioxoindoline-3-spiro-2′-pyrrolidine-3′-spiro-3′′-indoline-4′,4′-di­carbonitrile

In the title compound, C21H15N5O2, the pyrrolidine ring adopts a twist conformation. Both the oxindole rings are planar [maximum deviations of 0.076 (1) and 0.029 (1) Å in the two rings] and are oriented at a dihedral angle of 72.7 (1)°. The crystal structure is stabilized by C—H⋯O, N—H⋯O, N—H⋯N and C—H⋯π inter­actions

Novel Role of Prostate Apoptosis Response-4 Tumor Suppressor in B-Cell Chronic Lymphocytic Leukemia

Prostate apoptosis response-4 (Par-4), a proapoptotic tumor suppressor protein, is downregulated in many cancers including renal cell carcinoma, glioblastoma, endometrial, and breast cancer. Par-4 induces apoptosis selectively in various types of cancer cells but not normal cells. We found that chronic lymphocytic leukemia (CLL) cells from human patients and from Eµ-Tcl1 mice constitutively express Par-4 in greater amounts than normal B-1 or B-2 cells. Interestingly, knockdown of Par-4 in human CLL-derived Mec-1 cells results in a robust increase in p21/WAF1 expression and decreased growth due to delayed G1-to-S cell-cycle transition. Lack of Par-4 also increased the expression of p21 and delayed CLL growth in Eμ-Tcl1 mice. Par-4 expression in CLL cells required constitutively active B-cell receptor (BCR) signaling, as inhibition of BCR signaling with US Food and Drug Administration (FDA)–approved drugs caused a decrease in Par-4 messenger RNA and protein, and an increase in apoptosis. In particular, activities of Lyn, a Src family kinase, spleen tyrosine kinase, and Bruton tyrosine kinase are required for Par-4 expression in CLL cells, suggesting a novel regulation of Par-4 through BCR signaling. Together, these results suggest that Par-4 may play a novel progrowth rather than proapoptotic role in CLL and could be targeted to enhance the therapeutic effects of BCR-signaling inhibitors