Human Ontogeny of Drug Transporters: Review and Recommendations of the Pediatric Transporter Working Group

The critical importance of membrane-bound transporters in pharmacotherapy is widely recognized, but little is known about drug transporter activity in children. In this white paper, the Pediatric Transporter Working Group presents a systematic review of the ontogeny of clinically relevant membrane transporters (e.g., SLC, ABC superfamilies) in intestine, liver, and kidney. Different developmental patterns for individual transporters emerge, but much remains unknown. Recommendations to increase our understanding of membrane transporters in pediatric pharmacotherapy are presented

Identification of several small main-effect QTLs and a large number of epistatic QTLs for drought tolerance related traits in groundnut (Arachishypogaea L.)

Cultivated groundnut or peanut (Arachis hypogaea L.), an allotetraploid (2n = 4x = 40), is a self pollinated and widely grown crop in the semi-arid regions of the world. Improvement of drought tolerance is an important area of research for groundnut breeding programmes. Therefore, for the identification of candidate QTLs for drought tolerance, a comprehensive and refined genetic map containing 191 SSR loci based on a single mapping population (TAG 24 × ICGV 86031), segregating for drought and surrogate traits was developed. Genotyping data and phenotyping data collected for more than ten drought related traits in 2–3 seasons were analyzed in detail for identification of main effect QTLs (M-QTLs) and epistatic QTLs (E-QTLs) using QTL Cartographer, QTLNetwork and Genotype Matrix Mapping (GMM) programmes. A total of 105 M-QTLs with 3.48–33.36% phenotypic variation explained (PVE) were identified using QTL Cartographer, while only 65 M-QTLs with 1.3–15.01% PVE were identified using QTLNetwork. A total of 53 M-QTLs were such which were identified using both programmes. On the other hand, GMM identified 186 (8.54–44.72% PVE) and 63 (7.11–21.13% PVE), three and two loci interactions, whereas only 8 E-QTL interactions with 1.7–8.34% PVE were identified through QTLNetwork. Interestingly a number of co-localized QTLs controlling 2–9 traits were also identified. The identification of few major, many minor M-QTLs and QTL × QTL interactions during the present study confirmed the complex and quantitative nature of drought tolerance in groundnut. This study suggests deployment of modern approaches like marker-assisted recurrent selection or genomic selection instead of marker-assisted backcrossing approach for breeding for drought tolerance in groundnut

Experimental Infection of Cynomolgus Macaques (Macaca fascicularis) with Aerosolized Monkeypox Virus

Monkeypox virus (MPXV) infection in humans results in clinical symptoms very similar to ordinary smallpox. Aerosol is a route of secondary transmission for monkeypox, and a primary route of smallpox transmission in humans. Therefore, an animal model for aerosol exposure to MPXV is needed to test medical countermeasures. To characterize the pathogenesis in cynomolgus macaques (Macaca fascicularis), groups of macaques were exposed to four different doses of aerosolized MPXV. Blood was collected the day before, and every other day after exposure and assessed for complete blood count (CBC), clinical chemistry analysis, and quantitative PCR. Macaques showed mild anorexia, depression, and fever on day 6 post-exposure. Lymphadenopathy, which differentiates monkeypox from smallpox, was observed in exposed macaques around day 6 post-exposure. CBC and clinical chemistries showed abnormalities similar to human monkeypox cases. Whole blood and throat swab viral loads peaked around day 10, and in survivors, gradually decreased until day 28 post-exposure. Survival was not dose dependent. As such, doses of 4×104 PFU, 1×105 PFU, or 1×106 PFU resulted in lethality for 70% of the animals, whereas a dose of 4×105 PFU resulted in 85% lethality. Overall, cynomolgus macaques exposed to aerosolized MPXV develop a clinical disease that resembles that of human monkeypox. These findings provide a strong foundation for the use of aerosolized MPXV exposure of cynomolgus macaques as an animal model to test medical countermeasures against orthopoxviruses

Potential applications of nanotechnology in thermochemical conversion of microalgal biomass

The rapid decrease in fossil reserves has significantly increased the demand of renewable and sustainable energy fuel resources. Fluctuating fuel prices and significant greenhouse gas (GHG) emission levels have been key impediments associated with the production and utilization of nonrenewable fossil fuels. This has resulted in escalating interests to develop new and improve inexpensive carbon neutral energy technologies to meet future demands. Various process options to produce a variety of biofuels including biodiesel, bioethanol, biohydrogen, bio-oil, and biogas have been explored as an alternative to fossil fuels. The renewable, biodegradable, and nontoxic nature of biofuels make them appealing as alternative fuels. Biofuels can be produced from various renewable resources. Among these renewable resources, algae appear to be promising in delivering sustainable energy options. Algae have a high carbon dioxide (CO2) capturing efficiency, rapid growth rate, high biomass productivity, and the ability to grow in non-potable water. For algal biomass, the two main conversion pathways used to produce biofuel include biochemical and thermochemical conversions. Algal biofuel production is, however, challenged with process scalability for high conversion rates and high energy demands for biomass harvesting. This affects the viable achievement of industrial-scale bioprocess conversion under optimum economy. Although algal biofuels have the potential to provide a sustainable fuel for future, active research aimed at improving upstream and downstream technologies is critical. New technologies and improved systems focused on photobioreactor design, cultivation optimization, culture dewatering, and biofuel production are required to minimize the drawbacks associated with existing methods. Nanotechnology has the potential to address some of the upstream and downstream challenges associated with the development of algal biofuels. It can be applied to improve system design, cultivation, dewatering, biomass characterization, and biofuel conversion. This chapter discusses thermochemical conversion of microalgal biomass with recent advances in the application of nanotechnology to enhance the development of biofuels from algae. Nanotechnology has proven to improve the performance of existing technologies used in thermochemical treatment and conversion of biomass. The different bioprocess aspects, such as reactor design and operation, analytical techniques, and experimental validation of kinetic studies, to provide insights into the application of nanotechnology for enhanced algal biofuel production are addressed

Advances in genetics and molecular breeding of three legume crops of semi-arid tropics using next-generation sequencing and high-throughput genotyping technologies

Molecular markers are the most powerful genomic tools to increase the efficiency and precision of breeding practices for crop improvement. Progress in the development of genomic resources in the leading legume crops of the semi-arid tropics (SAT), namely, chickpea (Cicer arietinum), pigeonpea (Cajanus cajan) and groundnut (Arachis hypogaea), as compared to other crop species like cereals, has been very slow. With the advances in next-generation sequencing (NGS) and high-throughput (HTP) genotyping methods, there is a shift in development of genomic resources including molecular markers in these crops. For instance, 2,000 to 3,000 novel simple sequence repeats (SSR) markers have been developed each for chickpea, pigeonpea and groundnut. Based on Sanger, 454/FLX and Illumina transcript reads, transcriptome assemblies have been developed for chickpea (44,845 transcript assembly contigs, or TACs) and pigeonpea (21,434 TACs). Illumina sequencing of some parental genotypes of mapping populations has resulted in the development of 120 million reads for chickpea and 128.9 million reads for pigeonpea. Alignment of these Illumina reads with respective transcriptome assemblies have provided >10,000 SNPs each in chickpea and pigeonpea. A variety of SNP genotyping platforms including GoldenGate, VeraCode and Competitive Allele Specific PCR (KASPar) assays have been developed in chickpea and pigeonpea. By using above resources, the first-generation or comprehensive genetic maps have been developed in the three legume speciesmentioned above. Analysis of phenotyping data together with genotyping data has provided candidate markers for drought-tolerance-related root traits in chickpea, resistance to foliar diseases in groundnut and sterility mosaic disease (SMD) and fertility restoration in pigeonpea. Together with these traitassociated markers along with those already available, molecular breeding programmes have been initiated for enhancing drought tolerance, resistance to fusarium wilt and ascochyta blight in chickpea and resistance to foliar diseases in groundnut. These trait-associated robust markers along with other genomic resources including genetic maps and genomic resources will certainly accelerate crop improvement programmes in the SAT legum