Remote sensing in Michigan for land resource management

The Environmental Research Institute of Michigan is conducting a program whose goal is the large-scale adoption, by both public agencies and private interests in Michigan, of NASA earth-resource survey technology as an important aid in the solution of current problems in resource management and environmental protection. During the period from June 1975 to June 1976, remote sensing techniques to aid Michigan government agencies were used to achieve the following major results: (1) supply justification for public acquisition of land to establish the St. John's Marshland Recreation Area; (2) recommend economical and effective methods for performing a statewide wetlands survey; (3) assist in the enforcement of state laws relating to sand and gravel mining, soil erosion and sedimentation, and shorelands protection; (4) accomplish a variety of regional resource management actions in the East Central Michigan Planning and Development Region. Other tasks on which remote sensing technology was used include industrial and school site selection, ice detachment in the Soo Harbor, grave detection, and data presentation for wastewater management programs

Remote sensing in Michigan for land resource management

An extensive program was conducted to establish practical uses of NASA earth resource survey technology in meeting resource management problems throughout Michigan. As a result, a broad interest in and understanding of the usefulness of remote sensing methods was developed and a wide variety of applications was undertaken to provide information needed for informed decision making and effective action

Remote sensing in Michigan for land resource management

The utilization of NASA earth resource survey technology as an important aid in the solution of current problems in resource management and environmental protection in Michigan is discussed. Remote sensing techniques to aid Michigan government agencies were used to achieve the following results: (1) provide data on Great Lakes beach recession rates to establish shoreline zoning ordinances; (2) supply technical justification for public acquisition of land to establish the St. John's Marshland Recreation Area; (3) establish economical and effective methods for performing a statewide wetlands survey; (4) accomplish a variety of regional resource management actions in the Upper Peninsula; and (5) demonstrate improved soil survey methods. The project disseminated information on remote sensing technology and provided advice and assistance to a number of users in Michigan

MalDA, accelerating malaria drug discovery

The Malaria Drug Accelerator (MalDA) is a consortium of 15 leading scientific laboratories. The aim of MalDA is to improve and accelerate the early antimalarial drug discovery process by identifying new, essential, druggable targets. In addition, it seeks to produce early lead inhibitors that may be advanced into drug candidates suitable for preclinical development and subsequent clinical testing in humans. By sharing resources, including expertise, knowledge, materials, and reagents, the consortium strives to eliminate the structural barriers often encountered in the drug discovery process. Here we discuss the mission of the consortium and its scientific achievements, including the identification of new chemically and biologically validated targets, as well as future scientific directions

Prioritization of molecular targets for antimalarial drug discovery

There is a shift in antimalarial drug discovery from phenotypic screening toward target-based approaches, as more potential drug targets are being validated i

Remote sensing in Michigan for land resource management

The application of NASA earth resource survey technology to resource management and environmental protection in Michigan was investigated. Remote sensing techniques to aid Michigan government agencies were applied in the following activities: (1) land use inventory and management, (2) great lakes shorelands protection and management, (3) wetlands protection and management, and (4) soil survey. In addition, information was disseminated on remote sensing technology, and advice and assistance was provided to a number of users

Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism

The Plasmodium falciparum ABC transporter ABCI3 confers parasite strain-dependent pleiotropic antimalarial drug resistance

Widespread Plasmodium falciparum resistance to first-line antimalarials underscores the vital need to develop compounds with novel modes of action and identify new druggable targets. Here, we profile five compounds that potently inhibit P. falciparum asexual blood stages. Resistance selection studies with three carboxamide-containing compounds, confirmed by gene editing and conditional knockdowns, identify point mutations in the parasite transporter ABCI3 as the primary mediator of resistance. Selection studies with imidazopyridine or quinoline-carboxamide compounds also yield changes in ABCI3, this time through gene amplification. Imidazopyridine mode of action is attributed to inhibition of heme detoxification, as evidenced by cellular accumulation and heme fractionation assays. For the copy-number variation-selecting imidazopyridine and quinoline-carboxamide compounds, we find that resistance, manifesting as a biphasic concentration-response curve, can independently be mediated by mutations in the chloroquine resistance transporter PfCRT. These studies reveal the interconnectedness of P. falciparum transporters in overcoming drug pressure in different parasite strains