John H. Adams

Bio: John H. Adams is an academic researcher from University of South Florida. The author has contributed to research in topics: Plasmodium vivax & Plasmodium falciparum. The author has an hindex of 66, co-authored 354 publications receiving 16169 citations. Previous affiliations of John H. Adams include University of Alabama & University of Queensland.

Comparative genomics of the neglected human malaria parasite Plasmodium vivax

Abstract: The human malaria parasite Plasmodium vivax is responsible for 25-40% of the approximately 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non-human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species.

Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis

Abstract: INTRODUCTION Malaria remains a devastating global parasitic disease, with the majority of malaria deaths caused by the highly virulent Plasmodium falciparum . The extreme AT-bias of the P. falciparum genome has hampered genetic studies through targeted approaches such as homologous recombination or CRISPR-Cas9, and only a few hundred P. falciparum mutants have been experimentally generated in the past decades. In this study, we have used high-throughput piggyBac transposon insertional mutagenesis and quantitative insertion site sequencing (QIseq) to reach saturation-level mutagenesis of this parasite. RATIONALE Our study exploits the AT-richness of the P. falciparum genome, which provides numerous piggyBac transposon insertion targets within both gene coding and noncoding flanking sequences, to generate more than 38,000 P. falciparum mutants. At this level of mutagenesis, we could distinguish essential genes as nonmutable and dispensable genes as mutable. Subsequently, we identified 2680 genes essential for in vitro asexual blood-stage growth. RESULTS We calculated mutagenesis index scores (MISs) and mutagenesis fitness scores (MFSs) in order to functionally define the relative fitness cost of disruption for 5399 genes. A competitive growth phenotype screen confirmed that MIS and MFS were predictive of the fitness cost for in vitro asexual growth. Genes predicted to be essential included genes implicated in drug resistance—such as the “ K13 ” Kelch propeller, mdr , and dhfr-ts —as well as targets considered to be high value for drugs development, such as pkg and cdpk5 . The screen revealed essential genes that are specific to human Plasmodium parasites but absent from rodent-infective species, such as lipid metabolic genes that may be crucial to transmission commitment in human infections. MIS and MFS profiling provides a clear ranking of the relative essentiality of gene ontology (GO) functions in P. falciparum . GO pathways associated with translation, RNA metabolism, and cell cycle control are more essential, whereas genes associated with protein phosphorylation, virulence factors, and transcription are more likely to be dispensable. Last, we confirm that the proteasome-degradation pathway is a high-value druggable target on the basis of its high ratio of essential to dispensable genes, and by functionally confirming its link to the mode of action of artemisinin, the current front-line antimalarial. CONCLUSION Saturation-scale mutagenesis allows prioritization of intervention targets in the genome of the most important cause of malaria. The identification of more than 2680 essential genes, including ~1000 Plasmodium -conserved essential genes, will be valuable for antimalarial therapeutic research.

Global patterns of tectonic stress

Abstract: Regional patterns of present-day tectonic stress can be used to evaluate the forces acting on the lithosphere and to investigate intraplate seismicity. Most intraplate regions are characterized by a compressional stress regime; extension is limited almost entirely to thermally uplifted regions. In several plates the maximum horizontal stress is subparallel to the direction of absolute plate motion, suggesting that the forces driving the plates also dominate the stress distribution in the plate interior.

Arm Edema in Breast Cancer Patients

Abstract: The improvement in the life expectancy of women with breast cancer raises important questions about how to improve the quality of life for women sustaining complications of breast cancer treatment. In particular, attention to common problems, such as arm edema, is of critical importance. We reviewed published breast cancer guidelines and literature identified via MEDLINE(R) searches in an effort to summarize the research literature pertinent to management of breast cancer-related arm edema, including incidence, prevalence, and timing; risk factors; morbidity; prevention; diagnosis; and efficacy of nonpharmacologic and pharmacologic interventions. We found that arm edema is a common complication of breast cancer therapy that can result in substantial functional impairment and psychological morbidity. The risk of arm edema increases when axillary dissection and axillary radiation therapy are used. Recommendations for preventive measures, such as avoidance of trauma, are available, but these measures have not been well studied. Nonpharmacologic treatments, such as massage and exercise, have been shown to be effective therapies for lymphedema, but the effect of pharmacologic interventions remains uncertain. Comparing results across studies is complicated by the fact that the definitions of interventions and measures of outcomes and risk stratification vary substantially among studies. As arm edema becomes more prevalent with the increasing survival of breast cancer patients, further research is needed to evaluate the efficacy of preventive strategies and therapeutic interventions.

New Empirical Relationships among Magnitude, Rupture Length, Rupture Width, Rupture Area, and Surface Displacement

Abstract: Source parameters for historical earthquakes worldwide are compiled to develop a series of empirical relationships among moment magnitude ( M ), surface rupture length, subsurface rupture length, downdip rupture width, rupture area, and maximum and average displacement per event. The resulting data base is a significant update of previous compilations and includes the additional source parameters of seismic moment, moment magnitude, subsurface rupture length, downdip rupture width, and average surface displacement. Each source parameter is classified as reliable or unreliable, based on our evaluation of the accuracy of individual values. Only the reliable source parameters are used in the final analyses. In comparing source parameters, we note the following trends: (1) Generally, the length of rupture at the surface is equal to 75% of the subsurface rupture length; however, the ratio of surface rupture length to subsurface rupture length increases with magnitude; (2) the average surface displacement per event is about one-half the maximum surface displacement per event; and (3) the average subsurface displacement on the fault plane is less than the maximum surface displacement but more than the average surface displacement. Thus, for most earthquakes in this data base, slip on the fault plane at seismogenic depths is manifested by similar displacements at the surface. Log-linear regressions between earthquake magnitude and surface rupture length, subsurface rupture length, and rupture area are especially well correlated, showing standard deviations of 0.25 to 0.35 magnitude units. Most relationships are not statistically different (at a 95% significance level) as a function of the style of faulting: thus, we consider the regressions for all slip types to be appropriate for most applications. Regressions between magnitude and displacement, magnitude and rupture width, and between displacement and rupture length are less well correlated and have larger standard deviation than regressions between magnitude and length or area. The large number of data points in most of these regressions and their statistical stability suggest that they are unlikely to change significantly in response to additional data. Separating the data according to extensional and compressional tectonic environments neither provides statistically different results nor improves the statistical significance of the regressions. Regressions for cases in which earthquake magnitude is either the independent or the dependent parameter can be used to estimate maximum earthquake magnitudes both for surface faults and for subsurface seismic sources such as blind faults, and to estimate the expected surface displacement along a fault for a given size earthquake.

The Mechanics of Earthquakes and Faulting

Abstract: This essential reference for graduate students and researchers provides a unified treatment of earthquakes and faulting as two aspects of brittle tectonics at different timescales. The intimate connection between the two is manifested in their scaling laws and populations, which evolve from fracture growth and interactions between fractures. The connection between faults and the seismicity generated is governed by the rate and state dependent friction laws - producing distinctive seismic styles of faulting and a gamut of earthquake phenomena including aftershocks, afterslip, earthquake triggering, and slow slip events. The third edition of this classic treatise presents a wealth of new topics and new observations. These include slow earthquake phenomena; friction of phyllosilicates, and at high sliding velocities; fault structures; relative roles of strong and seismogenic versus weak and creeping faults; dynamic triggering of earthquakes; oceanic earthquakes; megathrust earthquakes in subduction zones; deep earthquakes; and new observations of earthquake precursory phenomena.

World-Wide Delivery of River Sediment to the Oceans

Abstract: New data and new estimates from old data show that rivers with large sediment loads (annual discharges greater than about $15 \times 10^{6}$ tons) contribute about $7 \times 10^{9}$ tons of suspended sediment to the ocean yearly. Extrapolating available data for all drainage basins, the total suspended sediment delivered by all rivers to the oceans is about $13.5 \times 10^{9}$ tons annually; bedload and flood discharges may account for an additional $1-2 \times 10^{9}$ tons. About 70% of this total is derived from southern Asia and the larger islands in the Pacific and Indian Oceans, where sediment yields are much greater than for other drainage basins.

Pragmatics of measuring recognition memory: applications to dementia and amnesia.

Abstract: SUMMARY This article has two purposes. The first is to describe four theoretical models of yesno recognition memory and present their associated measures of discrimination and response bias. These models are then applied to a set of data from normal subjects to determine which pairs of discrimination and bias indices show independence between discrimination and bias. The following models demonstrated independence: a two-highthreshold model, a signal detection model with normal distributions using d' and C (rather than beta), and a signal detection model with logistic distributions and a bias measure analogous to C. Cis defined as the distance of criterion from the intersection of the two underlying distributions. The second purpose is to use the indices from the acceptable models to characterize recognition memory deficits in dementia and amnesia, \bung normal subjects, Alzheimer's disease patients, and parkinsonian dementia patients were tested with picture recognition tasks with repeated study-test trials. Huntington's disease patients, mixed etiology amnesics, and age-matched normals were tested by Butters, Wolfe, Martone, Granholm, and Cermak (1985) using the same paradigm with word stimuli. Demented and amnesic patients produced distinctly different patterns of abnormal memory performance. Both groups of demented patients showed poor discrimination and abnormally liberal response bias for words (Huntington's disease) and pictures (Alzheimer's disease and parkinsonian dementia), whereas the amnesic patients showed the worst discrimination but normal response bias for words. Although both signal detection theory and twohigh-threshold discrimination parameters showed identical results, the bias measure from the two-high-threshold model was more sensitive to change than the bias measure (C) from signal detection theory. Three major points are emphasized. First, any index of recognition memory performance assumes an underlying model. Second, even acceptable models can lead to different conclusions about patterns of learning and forgetting. Third, efforts to characterize and ameliorate abnormal memory should address both discrimination and bias deficits.