Dopamine terminals from the ventral tegmental area gate intrinsic inhibition in the prefrontal cortex.

Spike frequency adaptation (SFA or accommodation) and calcium-activated potassium channels that underlie after-hyperpolarization potentials (AHP) regulate repetitive firing of neurons. Precisely how neuromodulators such as dopamine from the ventral tegmental area (VTA) regulate SFA and AHP (together referred to as intrinsic inhibition) in the prefrontal cortex (PFC) remains unclear. Using whole cell electrophysiology, we measured intrinsic inhibition in prelimbic (PL) layer 5 pyramidal cells of male adult rats. Results demonstrate that bath application of dopamine reduced intrinsic inhibition (EC50: 25.0 μmol/L). This dopamine action was facilitated by coapplication of cocaine (1 μmol/L), a blocker of dopamine reuptake. To evaluate VTA dopamine terminals in PFC slices, we transfected VTA dopamine cells of TH::Cre rats in vivo with Cre-dependent AAVs to express channelrhodopsin-2 (ChR2) or designer receptors exclusively activated by designer drugs (DREADDS). In PFC slices from these animals, stimulation of VTA terminals with either blue light to activate ChR2 or bath application of clozapine-N-oxide (CNO) to activate Gq-DREADDs produced a similar reduction in intrinsic inhibition in PL neurons. Electrophysiological recordings from cells expressing retrograde fluorescent tracers showed that this plasticity occurs in PL neurons projecting to the accumbens core. Collectively, these data highlight an ability of VTA terminals to gate intrinsic inhibition in the PFC, and under appropriate circumstances, enhance PL neuronal firing. These cellular actions of dopamine may be important for dopamine-dependent behaviors involving cocaine and cue-reward associations within cortical-striatal circuits

An analytical method for total heavy metal complexing agents in water and its application to water quality studies

The principle research accomplishment on this project was the development of several methods of analysis for low levels of complexing agents, particularly chelating agents. These species are very important in water quality. It is only very recently that their importance has become very apparent in areas such as heavy metal transport, algal growth, and toxicity of heavy metals. The first method developed, was an atomic absorption analysis of strong heavy metal chelating agents. This method is based upon the fact that when copper ion is added to a water sample and the pH adjusted to 10, the only copper that remains in solution is that which is in a complexed or chelated form. The precipitate which comes out of the solution at pH 10 contains the copper which is not complexed or chelated and is removed by filtration. The copper remaining in solution is measured by atomic absorption. This copper concentration is a measure of the amount of chelating agent in the water and is called the copper equivalent chelating capacity of the water. The method was used on a number of natural water samples. It was found, for example, that normal creek water contains about one milligram per liter copper equivalent chelating capacity. Water supporting algal growth typically contains about the same level. Raw sewage from a nonindustrial source typically contains around 3 milligrams per liter copper equivalent chelating capacity, whereas properly treated sewage effluent contains 1 milligram per liter or less. The method was extended to the analysis of cyanide ion, a water pollutant found in mining and metal processing effluents. It is applicable to cyanide and provides a simple and convenient method for the analysis of this pollutant. In the final few weeks of the project, a new method was developed in which the copper is solublized from a copper-containing chelating ion exchange resin. This method is much more rapid than the first method described, though somewhat more subject to interferences. It is applicable to automated procedures and as a detection system for chelating agents separated by liquid chromatography. It is extremely sensitive and can detect as little as 5x10^-7 millimoles of NTA. These applications of the method are being pursued under a USDI-OWRR matching grant starting on July 1, 1973.Project # A-056-MO Agreement # 14-31-0001-382

Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss

Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss (Bisphosphonates) will determine whether antiresorptive agents, in conjunction with the routine inflight exercise program, will protect ISS crewmembers from the regional decreases in bone mineral density documented on previous ISS missions

Domestication as innovation : the entanglement of techniques, technology and chance in the domestication of cereal crops

The origins of agriculture involved pathways of domestication in which human behaviours and plant genetic adaptations were entangled. These changes resulted in consequences that were unintended at the start of the process. This paper highlights some of the key innovations in human behaviours, such as soil preparation, harvesting and threshing, and how these were coupled with genetic ‘innovations’ within plant populations. We identify a number of ‘traps’ for early cultivators, including the needs for extra labour expenditure on crop-processing and soil fertility maintenance, but also linked gains in terms of potential crop yields. Compilations of quantitative data across a few different crops for the traits of nonshattering and seed size are discussed in terms of the apparently slow process of domestication, and parallels and differences between different regional pathways are identified. We highlight the need to bridge the gap between a Neolithic archaeobotanical focus on domestication and a focus of later periods on crop-processing activities and labour organization. In addition, archaeobotanical data provide a basis for rethinking previous assumptions about how plant genetic data should be related to the origins of agriculture and we contrast two alternative hypotheses: gradual evolution with low selection pressure versus metastable equilibrium that prolonged the persistence of ‘semi-domesticated’ populations. Our revised understanding of the innovations involved in plant domestication highlight the need for new approaches to collecting, modelling and integrating genetic data and archaeobotanical evidence

Were Fertile Crescent crop progenitors higher yielding than other wild species that were never domesticated?

During the origin of agriculture in the Fertile Crescent, the broad spectrum of wild plant species exploited by hunter-gatherers narrowed dramatically. The mechanisms responsible for this specialization and the associated domestication of plants are intensely debated. We investigated why some species were domesticated rather than others, and which traits they shared. We tested whether the progenitors of cereal and pulse crops, grown individually, produced a higher yield and less chaff than other wild grasses and legumes, thereby maximizing the return per seed planted and minimizing processing time. We compared harvest traits of species originating from the Fertile Crescent, including those for which there is archaeological evidence of deliberate collection. Unexpectedly, wild crop progenitors in both families had neither higher grain yield nor, in grasses, less chaff, although they did have larger seeds. Moreover, small-seeded grasses actually returned a higher yield relative to the mass of seeds sown. However, cereal progenitors had threefold fewer seeds per plant, representing a major difference in how seeds are packaged on plants. These data suggest that there was no intrinsic yield advantage to adopting large-seeded progenitor species as crops. Explaining why Neolithic agriculture was founded on these species, therefore, remains an important unresolved challenge

Cereal progenitors differ in stand harvest characteristics from related wild grasses

The domestication of crops in the Fertile Crescent began approximately 10,000 years ago indicating a change from a hunter-gatherer lifestyle to a sedentary, agriculture-based existence. The exploitation of wild plants changed during this transition, such that a small number of crops were domesticated from the broader range of species gathered from the wild. However, the reasons for this change are unclear. Previous studies have shown unexpectedly that crop progenitors are not consistently higher yielding than related wild grass species, when growing without competition. In this study, we replicate more closely natural competition within wild stands, using two greenhouse experiments to investigate whether cereal progenitors exhibit a greater seed yield per unit area than related wild species that were not domesticated. Stands of cereal progenitors do not provide a greater total seed yield per unit ground area than related wild species, but these crop progenitors do have greater reproductive efficiency than closely related wild species, with nearly twice the harvest index (the ratio of harvested seeds to total shoot dry mass). These differences arise because the progenitors have greater seed yield per tiller than closely related wild species, due to larger individual seed size but no reduction in seed number per tiller. The harvest characteristics of cereal progenitors may have made them a more attractive prospect than closely related wild species for the early cultivators who first planted these species, or could suggest an ecological filtering mechanism. Synthesis. Overall, we show that the maintenance of a high harvest index under competition, the packaging of seed in large tillers, and large seeds, consistently distinguish crop progenitors from closely related wild grass species. However, the archaeological significance of these findings remains unclear, since a number of more distantly related species, including wild oats, have an equally high or higher harvest index and yield than some of the progenitor species. Domestication of the earliest cereal crops from the pool of wild species available cannot therefore be explained solely by species differences in yield and harvest characteristics, and must also consider other plant traits

Novel Sources of Witchweed (Striga) Resistance from Wild Sorghum Accessions

Sorghum is a major food staple in sub-Saharan Africa (SSA), but its production is constrained by the parasitic plant Striga that attaches to the roots of many cereals crops and causes severe stunting and loss of yield. Away from cultivated farmland, wild sorghum accessions grow as weedy plants and have shown remarkable immunity to Striga. We sought to determine the extent of the resistance to Striga in wild sorghum plants. Our screening strategy involved controlled laboratory assays of rhizotrons, where we artificially infected sorghum with Striga, as well as field experiments at three sites, where we grew sorghum with a natural Striga infestation. We tested the resistance response of seven accessions of wild sorghum of the aethiopicum, drummondii, and arundinaceum races against N13, which is a cultivated Striga resistant landrace. The susceptible control was farmer-preferred variety, Ochuti. From the laboratory experiments, we found three wild sorghum accessions (WSA-1, WSE-1, and WSA-2) that had significantly higher resistance than N13. These accessions had the lowest Striga biomass and the fewest and smallest Striga attached to them. Further microscopic and histological analysis of attached Striga haustorium showed that wild sorghum accessions hindered the ingression of Striga haustorium into the host endodermis. In one of the resistant accessions (WSE-1), host and parasite interaction led to the accumulation of large amounts of secondary metabolites that formed a dark coloration at the interphase. Field experiments confirmed the laboratory screening experiments in that these same accessions were found to have resistance against Striga. In the field, wild sorghum had low Area under the Striga Number Progressive curve (AUSNPC), which measures emergence of Striga from a host over time. We concluded that wild sorghum accessions are an important reservoir for Striga resistance that could be used to expand the genetic basis of cultivated sorghum for resistance to the parasite