Global distribution and drivers of relative contributions among soil nitrogen sources to terrestrial plants.

Soil extractable nitrate, ammonium, and organic nitrogen (N) are essential N sources supporting primary productivity and regulating species composition of terrestrial plants. However, it remains unclear how plants utilize these N sources and how surface-earth environments regulate plant N utilization. Here, we establish a framework to analyze observational data of natural N isotopes in plants and soils globally, we quantify fractional contributions of soil nitrate (fNO3-), ammonium (fNH4+), and organic N (fEON) to plant-used N in soils. We find that mean annual temperature (MAT), not mean annual precipitation or atmospheric N deposition, regulates global variations of fNO3-, fNH4+, and fEON. The fNO3- increases with MAT, reaching 46% at 28.5 °C. The fNH4+ also increases with MAT, achieving a maximum of 46% at 14.4 °C, showing a decline as temperatures further increase. Meanwhile, the fEON gradually decreases with MAT, stabilizing at about 20% when the MAT exceeds 15 °C. These results clarify global plant N-use patterns and reveal temperature rather than human N loading as a key regulator, which should be considered in evaluating influences of global changes on terrestrial ecosystems.

Greenhouse gas emissions from US irrigation pumping and implications for climate-smart irrigation policy.

Irrigation reduces crop vulnerability to drought and heat stress and thus is a promising climate change adaptation strategy. However, irrigation also produces greenhouse gas emissions through pump energy use. To assess potential conflicts between adaptive irrigation expansion and agricultural emissions mitigation efforts, we calculated county-level emissions from irrigation energy use in the US using fuel expenditures, prices, and emissions factors. Irrigation pump energy use produced 12.6 million metric tonnes CO2e in the US in 2018 (90% CI: 10.4, 15.0), predominantly attributable to groundwater pumping. Groundwater reliance, irrigated area extent, water demand, fuel choice, and electrical grid emissions intensity drove spatial heterogeneity in emissions. Due to heavy reliance on electrical pumps, projected reductions in electrical grid emissions intensity are estimated to reduce pumping emissions by 46% by 2050, with further reductions possible through pump electrification. Quantification of irrigation-related emissions will enable targeted emissions reduction efforts and climate-smart irrigation expansion.

Sustainable irrigation and climate feedbacks.

Agricultural irrigation induces greenhouse gas emissions directly from soils or indirectly through the use of energy or construction of dams and irrigation infrastructure, while climate change affects irrigation demand, water availability and the greenhouse gas intensity of irrigation energy. Here, we present a scoping review to elaborate on these irrigation-climate linkages by synthesizing knowledge across different fields, emphasizing the growing role climate change may have in driving future irrigation expansion and reinforcing some of the positive feedbacks. This Review underscores the urgent need to promote and adopt sustainable irrigation, especially in regions dominated by strong, positive feedbacks.

Intrinsic water-use efficiency influences establishment in Encelia farinosa.

We describe establishment of Encelia farinosa, a drought-deciduous shrub common to the Mojave and Sonoran Deserts, based on annual observations of two populations between 1980 and 2020. Only 11 establishment events of 50 + yearlings (0.02-0.03 individuals m-2) occurred during this monitoring period; in 68% of the years fewer than 10 yearlings were established. Yearling survival to adulthood (age 4) ranged from 88 to 5% and was significantly related to cumulative precipitation. Juvenile survival rates were lowest during the current megadrought period. We calculated intrinsic water-use efficiency (iWUE) and observed the widest variations in iWUE values among the youngest plants. Among juveniles, surviving yearlings with the lowest iWUE values exhibited upward ontogenetic shifts in iWUE values, whereas those yearlings with the highest initial iWUE values exhibited little if any change. Juvenile size, higher iWUE values, and greater likelihood of surviving were all positively related with each other over the past several decades. Furthermore, iWUE and photosynthetic capacity were positively related to each other, providing a mechanistic explanation for why increased iWUE values among juveniles could lead to greater survival rates and to larger plants under water-deficit conditions. We posit that there is bi-directional selection for genotypic variations in iWUE values among E. farinosa and that this variation is selected for because of interannual environmental heterogeneity in precipitation and VPD associated with both high- and low-frequency climate cycles. Extreme drought cycles may favor plants with higher iWUE values, whereas more mesic periods may allow for greater persistence of lower iWUE genotypes.

Rapid increases in shrubland and forest intrinsic water-use efficiency during an ongoing megadrought.

Globally, intrinsic water-use efficiency (iWUE) has risen dramatically over the past century in concert with increases in atmospheric CO2 concentration. This increase could be further accelerated by long-term drought events, such as the ongoing multidecadal "megadrought" in the American Southwest. However, direct measurements of iWUE in this region are rare and largely constrained to trees, which may bias estimates of iWUE trends toward more mesic, high elevation areas and neglect the responses of other key plant functional types such as shrubs that are dominant across much of the region. Here, we found evidence that iWUE is increasing in the Southwest at one of the fastest rates documented due to the recent drying trend. These increases were particularly large across three common shrub species, which had a greater iWUE sensitivity to aridity than Pinus ponderosa, a common tree species in the western United States. The sensitivity of both shrub and tree iWUE to variability in atmospheric aridity exceeded their sensitivity to increasing atmospheric [CO2]. The shift to more water-efficient vegetation would be, all else being equal, a net positive for plant health. However, ongoing trends toward lower plant density, diminished growth, and increasing vegetation mortality across the Southwest indicate that this increase in iWUE is unlikely to offset the negative impacts of aridification.

Long-term nitrogen isotope dynamics in Encelia farinosa reflect plant demographics and climate.

While plant δ15 N values have been applied to understand nitrogen (N) dynamics, uncertainties regarding intraspecific and temporal variability currently limit their application. We used a 28 yr record of δ15 N values from two Mojave Desert populations of Encelia farinosa to clarify sources of population-level variability. We leveraged > 3500 foliar δ15 N observations collected alongside structural, physiological, and climatic data to identify plant and environmental contributors to δ15 N values. Additional sampling of soils, roots, stems, and leaves enabled assessment of the distribution of soil N content and δ15 N, intra-plant fractionations, and relationships between soil and plant δ15 N values. We observed extensive within-population variability in foliar δ15 N values and found plant age and foliar %N to be the strongest predictors of individual δ15 N values. There were consistent differences between root, stem, and leaf δ15 N values (spanning c. 3‰), but plant and bulk soil δ15 N values were unrelated. Plant-level variables played a strong role in influencing foliar δ15 N values, and interannual relationships between climate and δ15 N values were counter to previously recognized spatial patterns. This long-term record provides insights regarding the interpretation of δ15 N values that were not available from previous large-scale syntheses, broadly enabling more effective application of foliar δ15 N values.

Interactions among intrinsic water-use efficiency and climate influence growth and flowering in a common desert shrub.

Plants make leaf-level trade-offs between photosynthetic carbon assimilation and water loss, and the optimal balance between the two is dependent, in part, on water availability. "Conservative" water-use strategies, in which minimizing water loss is prioritized over assimilating carbon, tend to be favored in arid environments, while "aggressive" water-use strategies, in which carbon assimilation is prioritized over water conservation, are often favored in mesic environments. When derived from foliar carbon isotope ratios, intrinsic water-use efficiency (iWUE) serves as a seasonally integrated indicator of the balance of carbon assimilation to water loss at the leaf level. Here, we used a multi-decadal record of annual iWUE, growth, and flowering from a single population of Encelia farinosa in the Mojave Desert to evaluate the effect of iWUE on plant performance across interannual fluctuations in water availability. We identified substantial variability in iWUE among individuals and found that iWUE interacted with water availability to significantly influence growth and flowering. However, the relationships between iWUE, water availability, and plant performance did not universally suggest that "conservative" water-use strategies were advantageous in dry years or that "aggressive" strategies were advantageous in wet years. iWUE was positively related to the odds of growth regardless of water availability and to the odds of flowering in dry years, but negatively related to growth rates in dry years. In addition, we found that leaf nitrogen content affected interannual plant performance and that an individual's iWUE plasticity in response to fluctuations in aridity was negatively related to early life drought survival and growth.

Multidecadal records of intrinsic water-use efficiency in the desert shrub Encelia farinosa reveal strong responses to climate change.

While tree rings have enabled interannual examination of the influence of climate on trees, this is not possible for most shrubs. Here, we leverage a multidecadal record of annual foliar carbon isotope ratio collections coupled with 39 y of survey data from two populations of the drought-deciduous desert shrub Encelia farinosa to provide insight into water-use dynamics and climate. This carbon isotope record provides a unique opportunity to examine the response of desert shrubs to increasing temperature and water stress in a region where climate is changing rapidly. Population mean carbon isotope ratios fluctuated predictably in response to interannual variations in temperature, vapor pressure deficit, and precipitation, and responses were similar among individuals. We leveraged the well-established relationships between leaf carbon isotope ratios and the ratio of intracellular to ambient CO2 concentrations to calculate intrinsic water-use efficiency (iWUE) of the plants and to quantify plant responses to long-term environmental change. The population mean iWUE value increased by 53 to 58% over the study period, much more than the 20 to 30% increase that has been measured in forests [J. Peñuelas, J. G. Canadell, R. Ogaya, Glob. Ecol. Biogeogr. 20, 597-608 (2011)]. Changes were associated with both increased CO2 concentration and increased water stress. Individuals whose lifetimes spanned the entire study period exhibited increases in iWUE that were very similar to the population mean, suggesting that there was significant plasticity within individuals rather than selection at the population scale.

Distinguishing the region-of-origin of roasted coffee beans with trace element ratios.

Determining coffee region-of-origin is most appropriately addressed through analyses of the product available to the consumer. We analyzed the concentrations of 44 trace elements in 53 samples of roasted Arabica coffee beans (Coffea arabica) from 21 different countries. Variations in absolute elemental concentrations of coffee beans arise through varying degrees of roasting (from green through dark roasts). Since trace elements are not volatilized at roasting temperatures, we conducted analyses of element ratios to evaluate concentration-related differences among beans of different origins. We used kernel density estimates to compare the distributions of 1892 element ratios for each of these countries with the combined distribution of coffee samples from the other countries. Using this quantitative approach, we demonstrated that many of the world's coffee-producing regions can be distinguished from other regions of the world on the basis of element ratios.

A predictive spatial model for roasted coffee using oxygen isotopes of α-cellulose.

RATIONALE: Fraudulent region-of-origin labeling is a concern for high-value, globally traded commodities such as coffee. The oxygen isotope ratio of cellulose is a useful geographic tracer, as it integrates climate and source water signals. A predictive spatial model ("isoscape") of the δ18 O values of coffee bean cellulose is generated to evaluate coffee region-of-origin claims. METHODS: The oxygen isotope ratio of α-cellulose extracted from roasted coffee beans was measured via high-temperature conversion elemental analyzer/isotope ratio mass spectrometry (TC-EA/IRMS) and used to calculate the δ18 O value of coffee bean water. The 18 O enrichment of coffee bean water relative to the δ18 O value of local precipitation was modeled as a function of local temperature and humidity. This function was incorporated into a mechanistic model of cellulose δ18 O values to predict the δ18 O values of coffee bean cellulose across coffee-producing regions globally. RESULTS: The δ18 O values of analyzed coffee bean cellulose ranged from approximately +22‰ to +42‰ (V-SMOW). As expected, coffees grown in the same region tended to have similar isotope ratios, and the δ18 O value of coffee bean cellulose was generally higher than the δ18 O value of modeled stem cellulose for the region. Modeled δ18 O values of coffee cellulose were within ±2.3‰ of the measured δ18 O value of coffee cellulose. CONCLUSIONS: The oxygen isotope ratio of coffee bean cellulose is a useful indicator of region-of-origin and varies predictably in response to climatic factors and precipitation isotope ratios. The isoscape of coffee bean cellulose δ18 O values from this study provides a quantitative tool that can be applied to region-of-origin verification of roasted coffee at the point-of-sale.

The La protein counteracts cisplatin-induced cell death by stimulating protein synthesis of anti-apoptotic factor Bcl2.

Up-regulation of anti-apoptotic factors is a critical mechanism of cancer cell resistance and often counteracts the success of chemotherapeutic treatment. Herein, we identified the cancer-associated RNA-binding protein La as novel factor contributing to cisplatin resistance. Our data demonstrate that depletion of the RNA-binding protein La in head and neck squamous cell carcinoma cells (HNSCC) increases the sensitivity toward cisplatin-induced cell death paralleled by reduced expression of the anti-apoptotic factor Bcl2. Furthermore, it is shown that transient expression of Bcl2 in La-depleted cells protects against cisplatin-induced cell death. By dissecting the underlying mechanism we report herein, that the La protein is required for Bcl2 protein synthesis in cisplatin-treated cells. The RNA chaperone La binds in close proximity to the authentic translation start site and unwinds a secondary structure embedding the authentic AUG. Altogether, our data support a novel model, whereby cancer-associated La protein contributes to cisplatin resistance by stimulating the translation of anti-apoptotic factor Bcl2 in HNSCC cells.

Novel RNA chaperone domain of RNA-binding protein La is regulated by AKT phosphorylation.

The cellular function of the cancer-associated RNA-binding protein La has been linked to translation of viral and cellular mRNAs. Recently, we have shown that the human La protein stimulates IRES-mediated translation of the cooperative oncogene CCND1 in cervical cancer cells. However, there is little known about the underlying molecular mechanism by which La stimulates CCND1 IRES-mediated translation, and we propose that its RNA chaperone activity is required. Herein, we show that La binds close to the CCND1 start codon and demonstrate that La's RNA chaperone activity can change the folding of its binding site. We map the RNA chaperone domain (RCD) within the C-terminal region of La in close proximity to a novel AKT phosphorylation site (T389). Phosphorylation at T389 by AKT-1 strongly impairs its RNA chaperone activity. Furthermore, we demonstrate that the RCD as well as T389 is required to stimulate CCND1 IRES-mediated translation in cells. In summary, we provide a model whereby a novel interplay between RNA-binding, RNA chaperoning and AKT phosphorylation of La protein regulates CCND1 IRES-mediated translation.

Mechanisms of oncostatin M-induced pulmonary inflammation and fibrosis.

Oncostatin M (OSM), an IL-6 family cytokine, has been implicated in a number of biological processes including the induction of inflammation and the modulation of extracellular matrix. In this study, we demonstrate that OSM is up-regulated in the bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and scleroderma, and investigate the pathological consequences of excess OSM in the lungs. Delivery of OSM to the lungs of mice results in a significant recruitment of inflammatory cells, as well as a dose-dependent increase in collagen deposition in the lungs, with pathological correlates to characteristic human interstitial lung disease. To better understand the relationship between OSM-induced inflammation and OSM-induced fibrosis, we used genetically modified mice and show that the fibrotic response is largely independent of B and T lymphocytes, eosinophils, and mast cells. We further explored the mechanisms of OSM-induced inflammation and fibrosis using both protein and genomic array approaches, generating a "fibrotic footprint" for OSM that shows modulation of various matrix metalloproteinases, extracellular matrix components, and cytokines previously implicated in fibrosis. In particular, although the IL-4/IL-13 and TGF-beta pathways have been shown to be important and intertwined of fibrosis, we show that OSM is capable of inducing lung fibrosis independently of these pathways. The demonstration that OSM is a potent mediator of lung inflammation and extracellular matrix accumulation, combined with the up-regulation observed in patients with pulmonary fibrosis, may provide a rationale for therapeutically targeting OSM in human disease.

Intradermal administration of thymic stromal lymphopoietin induces a T cell- and eosinophil-dependent systemic Th2 inflammatory response.

The epithelial-derived cytokine thymic stromal lymphopoietin (TSLP) is sufficient to induce asthma or atopic dermatitis-like phenotypes when selectively overexpressed in transgenic mice, or when driven by topical application of vitamin D3 or low-calcemic analogues. Although T and B cells have been reported to be dispensable for the TSLP-induced inflammation in these models, little is known about the downstream pathways or additional cell types involved in the inflammatory response driven by TSLP. To characterize the downstream effects of TSLP in vivo, we examined the effects of exogenous administration of TSLP protein to wild-type and genetically deficient mice. TSLP induced a systemic Th2 inflammatory response characterized by increased circulating IgE and IgG1 as well as increased draining lymph node size and cellularity, Th2 cytokine production in draining lymph node cultures, inflammatory cell infiltrates, epithelial hyperplasia, subcuticular fibrosis, and up-regulated Th2 cytokine and chemokine messages in the skin. Responses to TSLP in various genetically deficient mice demonstrated T cells and eosinophils were required, whereas mast cells and TNF-alpha were dispensable. TSLP-induced responses were significantly, but not completely reduced in IL-4- and IL-13-deficient mice. These results shed light on the pathways and cell types involved in TSLP-induced inflammation.

BTNL2, a butyrophilin/B7-like molecule, is a negative costimulatory molecule modulated in intestinal inflammation.

Butyrophilin-like 2 (BTNL2) is a butyrophilin family member with homology to the B7 costimulatory molecules, polymorphisms of which have been recently associated through genetic analyses to sporadic inclusion body myositis and sarcoidosis. We have characterized the full structure, expression, and function of BTNL2. Structural analysis of BTNL2 shows a molecule with an extracellular region containing two sets of two Ig domains, a transmembrane region, and a previously unreported cytoplasmic tail. Unlike most other butyrophilin members, BTNL2 lacks the prototypical B30.2 ring domain. TaqMan and Northern blot analysis indicate BTNL2 is predominantly expressed in digestive tract tissues, in particular small intestine and Peyer's patches. Immunohistochemistry with BTNL2-specific Abs further localizes BTNL2 to epithelial and dendritic cells within these tissues. Despite its homology to the B7 family, BTNL2 does not bind any of the known B7 family receptors such as CD28, CTLA-4, PD-1, ICOS, or B and T lymphocyte attenuator. Because of its localization in the gut and potential role in the immune system, BTNL2 expression was analyzed in a mouse model of inflammatory bowel disease. BTNL2 is overexpressed during both the asymptomatic and symptomatic phase of the Mdr1a knockout model of spontaneous colitis. In functional assays, soluble BTNL2-Fc protein inhibits the proliferation of murine CD4(+) T cells from the spleen, mesenteric lymph node, and Peyer's patch. In addition, BTNL2-Fc reduces proliferation and cytokine production from T cells activated by anti-CD3 and B7-related protein 1. These data suggest a role for BTNL2 as a negative costimulatory molecule with implications for inflammatory disease.

C-reactive protein may be increased in migraine patients who present with complex clinical features.

OBJECTIVES: Stroke risk is increased in migraine, the basis of which remains to be established. C-reactive protein (CRP) is a marker of cerebrovascular disease, suggesting in part an inflammatory mechanism. Because attacks of migraine may involve repeated sterile vascular inflammation, we measured CRP in migraine patients. METHODS: Retrospective review was conducted of 60 randomly sampled charts of patients with the diagnosis of migraine without aura (MwoA, n = 29) and migraine with aura (MwA, n = 31), in which CRP was recorded as part of the differential diagnostic evaluation. CRP was measured by standard commercial laboratory methods; high sensitivity CRP (hs-CRP) values above 3mg/L were considered abnormal. RESULTS: Elevated hs-CRP was found in 43% of all patients (26 of 60). In MwoA, of 29 subjects, abnormal hs-CRP was recorded in 16; in 10 no other conditions were found to explain the abnormality. In MwA, of 31 subjects, abnormal CRP was recorded in 10; in 5 no other condition could explain the abnormality. No associations were found between other demographic or clinical features. CONCLUSIONS: CRP may be abnormal in MwoA and MwA patients who present with atypical, severe, or complex clinical features that require extensive differential diagnostic investigation.

Probing hydrogen-bonding interactions in the active site of medium-chain acyl-CoA dehydrogenase using Raman spectroscopy.

The role of the oxyanion hole in the reaction catalyzed by pig medium-chain acyl-CoA dehydrogenase (pMCAD) has been investigated using enzyme reconstituted with 2'-deoxy-FAD. The k(cat) (18.8 +/- 0.5 s(-1)) and K(m) (2.5 +/- 0.4 microM) values for the oxidation of n-octanoyl-CoA (C(8)-CoA) by WT pMCAD recombinantly expressed in Escherichia coli are similar to those of native pMCAD isolated from pig kidney. In agreement with previous studies [Engst et al. (1999) Biochemistry 38, 257-267], reconstitution of the WT enzyme with 2'-deoxy-FAD causes a large (400-fold) decrease in k(cat) but has little effect on K(m). To investigate the molecular basis for the alterations in activity resulting from changes in hydrogen bonding between the substrate and the enzyme's oxyanion hole, the structure of the product analogue hexadienoyl-CoA (HD-CoA) bound to the 2'-deoxy-FAD-reconstituted enzyme has been probed by Raman spectroscopy. Importantly, while WT pMCAD causes a 27 cm(-1) decrease in the vibrational frequency of the HD enone band, from 1595 to 1568 cm(-1), the enone band is only shifted 10 cm(-1) upon binding HD-CoA to 2'-deoxy-FAD pMCAD. Thus, removal of the 2'-ribityl hydroxyl group results in a substantial reduction in the ability of the enzyme to polarize the ground state of the ES complex. On the basis of an analysis of a similar system, it is estimated that ground state destabilization is reduced by up to 17 kJ mol(-1), while the activation energy for the reaction is raised 15 kJ mol(-1). In addition, removal of the 2'-ribityl hydroxyl reduces the redox potential shift that is induced by HD-CoA binding from 18 to 11 kJ mol(-1). Consequently, while ligand polarization caused by hydrogen bonding in the oxyanion hole is intimately linked to substrate turnover, additional factors must be responsible for ligand-induced changes in redox potential. Finally, while replacement of the catalytic base E376 with Gln abolishes the ability of the enzyme to catalyze substrate oxidation and to catalyze the exchange of the C(8)-CoA alpha-protons with solvent deuterium, the 2'-deoxy-FAD-reconstituted enzyme catalyzes alpha-proton exchange at a rate (k(exc)) of 0.085 s(-1), which is only 4-fold slower than k(exc) for WT pMCAD (0.35 s(-1)). Thus, either the oxyanion hole plays only a minor role in stabilizing the transition state for alpha-proton exchange, in contrast to its role in substrate oxidation, or the value of k(exc) for WT pMCAD reflects a process such as exchange of the E376 COOH proton with solvent.

Endothelin-A receptors and NO mediate decrease in arterial pressure during recovery from restraint.

We investigated the role of central endothelin-A (ET(A)) receptors and nitric oxide (NO) in regulating arterial pressure during restraint stress and recovery from stress. Rats received intracerebroventricular (icv) injections of the ET(A) receptor antagonist BQ123 (24 microg/kg) and were then subjected to two restraint-rest cycles (1 h of restraint and 1 h of rest/cycle). Although mean arterial pressure (MAP) values in BQ123-treated and control rats increased at the onset of restraint and remained elevated during restraint, MAP values in BQ123-treated rats were consistently greater than in control rats. During rest periods, MAP values in control rats decreased to below baseline levels, whereas those in BQ123-treated rats remained significantly higher. NO content was decreased in the brain stems of BQ123-treated compared with control rats after the 4-h protocol. Injections (icv) of the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine (L-NNA) eliminated the decreases in MAP values during rest periods in both BQ123-treated and control rats. Inhibition of neuronal NOS with icv injection of 7-nitroindazole sodium salt resulted in MAP values intermediate between control rats and rats receiving L-NNA. These results support the hypothesis that endothelin acts through ET(A) receptors in the brain, possibly via release of NO, to decrease arterial pressure during restraint and recovery from restraint.

The effects of L-dihydroxyphenylalanine on alertness and mood in alpha-methyl-para-tyrosine-treated healthy humans. Further evidence for the role of catecholamines in arousal and anxiety.

Treatment with alpha-methyl-para-tyrosine (AMPT), a catecholamine synthesis inhibitor, has been shown to produce pronounced increases in sleepiness and mild increases in negative mood and anxiety when administered to healthy male adults. The present study was conducted to ascertain whether these effects of AMPT are secondary to decreases in brain catecholamines or whether they represent nonspecific drug effects. Forty-one healthy males were randomized to one of four treatment groups. (1) Treatment with AMPT alone (AMPT/placebo); (2) treatment with AMPT plus L-dopa/carbidopa (AMPT plus L-dopa/carbidopa); (3) treatment with L-dopa/carbidopa alone (placebo plus L-dopa/carbidopa); or (4) treatment with placebo alone (placebo plus placebo). Repeated measures of alertness, mood, and anxiety were obtained over a three-day period of drug treatment and following drug discontinuation. As before, AMPT treatment led to increased sleepines. In addition, AMPT treatment led to decreased calmness, increased tension and anger, and a trend for increased depression. Replacement of catecholamine stores with L-dopa reversed the effects of AMPT and was associated with a more rapid recovery from AMPT's effects. These findings indicate that AMPT's effects on alertness and anxiety are catecholamine-specific. Further, they provide additional evidence that catecholamines are involved in the regulation of normal states of arousal, and they are consistent with the view that brain catecholaminergic dysregulation is involved in pathological anxiety states.

Initial clinical assessment of the comatose patient: cerebral malaria vs. meningitis.

One hundred twenty-one Liberian children were admitted in coma to the ELWA Hospital, Monrovia, Liberia. Admitting diagnoses, before lumbar puncture, were compared with discharge diagnoses. Ninety-four children were discharged with a final diagnosis of cerebral malaria and 27 with a diagnosis of meningitis. The admitting diagnosis was correct in 76.6% (72 of 94) of patients with cerebral malaria and 59.3% (16 of 27) of patients with meningitis. The cerebrospinal fluid leukocyte count was the single most significant factor in determining the correct diagnosis. Without the cerebrospinal fluid analysis, the discriminant accuracy (77%), i.e. definitive separation of the two illnesses, was comparable to the physician's admission diagnosis (73%). Other data contributing to the differential diagnosis of cerebral malaria and meningitis included the number of days of fever before admission, the presence or absence of nuchal rigidity, fontanelle fullness and peripheral blood malaria smear. Mortality rates for cerebral malaria and meningitis were 14.9 and 29.6%, respectively. These data suggest that physicians cannot reliably discriminate between cerebral malaria and meningitis without cerebrospinal fluid analysis.