Rap1b facilitates NK cell functions via IQGAP1-mediated signalosomes

Rap1 GTPases control immune synapse formation and signaling in lymphocytes. However, the precise molecular mechanism by which Rap1 regulates natural killer (NK) cell activation is not known. Using Rap1a or Rap1b knockout mice, we identify Rap1b as the major isoform in NK cells. Its absence significantly impaired LFA1 polarization, spreading, and microtubule organizing center (MTOC) formation in NK cells. Neither Rap1 isoform was essential for NK cytotoxicity. However, absence of Rap1b impaired NKG2D, Ly49D, and NCR1-mediated cytokine and chemokine production. Upon activation, Rap1b colocalized with the scaffolding protein IQGAP1. This interaction facilitated sequential phosphorylation of B-Raf, C-Raf, and ERK1/2 and helped IQGAP1 to form a large signalosome in the perinuclear region. These results reveal a previously unrecognized role for Rap1b in NK cell signaling and effector functions

Resistance reversal action of ketoconazole against mefloquine resistance of Plasmodium yoelii nigeriensis

Ketoconazole at 200 mg/kg dose has been found to exert marginal antimalarial action against multidrug resistant (MDR) Plasmodium yoelii nigeriensis (P. yoelii nigeriensis) in Swiss mice with 25% protection (2/8 mice) while at lower Ketoconazole dose i.e., 75-100 mg/kg, 14.28% mice were protected. Mefloquine (MFQ) (at 8 and 16 mg/kg) exerted suppressive action against MDR P. yoelii nigeriensis resulting in 25 and 14.28% protection of mice respectively. Combined treatment with Ketoconazole and mefloquine resulted in protection of 5/6 mice (83.33%) at MFQ 4 mg/kg + Ketoconazole 100 mg/kg dose, 7/8 (87.5%) mice at MFQ 8 mg/kg + Ketoconazole 20 mg/kg dose and 5/7 (71.42%) mice at MFQ 16 mg/kg + Ketoconazole 25 mg/kg dose and 5/6 (83.33%) mice at MFQ 16 mg/kg + Ketoconazole 100 mg/kg dose. Ketoconazole has been found to enhance the protective effect of mefloquine against MFQ resistant P. yoelii nigeriensis resulting in 66-88% protection of the mice treated with the appropriate combinations. The combination also increased suppression of parasitaemia at different times. The Ketoconazole combination with MFQ significantly increased the mean survival time of the treated mice compared to individual drugs alone. The study shows that Ketoconazole when administered with MFQ exerts bio-enhancing action against mefloquine resistance of MDR P. yoelii nigeriensis

Morphological and Humidity Sensing Studies of WO3 Mixed with ZnO and TiO2 Powders

This paper reports resistive type humidity sensing properties of composite powder of WO3, ZnO and TiO2 taken in the ratio of 8:2:1. Tungsten oxide powder has been obtained by oxidizing Tungsten powder (Lobachemie, 99 % pure) at 600 0C. 250 mg of ZnO (qualigens, 99% pure) and 125 mg of TiO2 (qualigens, 98% pure) have been mixed with 1 gram of WO3. Pellet of this powder mixture has been made at pressure of 3 tones for half an hour. The pellet has been annealed at temperatures of 300 0C, 400 0C and 500 0C. Humidity sensing application of pellet has been studied in a specially designed chamber. Standard solution of potassium sulphate has been used as humidifier and potassium hydroxide as de-humidifier. Variation in resistances has been noted using Sinometre (MΩ range,VC 9808). Relative humidity is measured using standard hygrometer (Huger, Germany). It has been observed that as relative humidity increases, there is decrease in the resistance of the pellet. After annealing of sample at each temperature, it has been exposed to humidity in the chamber. The mean sensitivity of the pellet is calculated for each annealing temperature. It has been observed that as annealing temperature increases from 300 0C to 500 0C, mean sensitivity increases. This composite material carries a good scope for the development of resistive type humidity sensor