Vaccination of cattle with the N terminus of LppQ of Mycoplasma mycoides subsp. mycoides results in type III immune complex disease upon experimental infection.

Contagious bovine pleuropneumonia (CBPP) is a serious respiratory disease of cattle caused by Mycoplasma mycoides subsp. mycoides. Current vaccines against CBPP induce short-lived immunity and can cause severe postvaccine reactions. Previous studies have identified the N terminus of the transmembrane lipoprotein Q (LppQ-N') of M. mycoides subsp. mycoides as the major antigen and a possible virulence factor. We therefore immunized cattle with purified recombinant LppQ-N' formulated in Freund's adjuvant and challenged them with M. mycoides subsp. mycoides. Vaccinated animals showed a strong seroconversion to LppQ, but they exhibited significantly enhanced postchallenge glomerulonephritis compared to the placebo group (P = 0.021). Glomerulonephritis was characterized by features that suggested the development of antigen-antibody immune complexes. Clinical signs and gross pathological scores did not significantly differ between vaccinated and placebo groups. These findings reveal for the first time the pathogenesis of enhanced disease as a result of antibodies against LppQ during challenge and also argue against inclusion of LppQ-N' in a future subunit vaccine for CBPP.

Contrasting PT paths within the Barchi-Kol UHP terrain (Kokchetav Complex): Implications for subduction and exhumation of continental crust

The Barchi-Kol terrain is a classic locality of ultrahigh-pressure (UHP) metamorphism within the Kokchetav metamorphic belt. We provide a detailed and systematic characterization of four metasedimentary samples using dominant mineral assemblages, mineral inclusions in zircon and monazite, garnet zonation with respect to major and trace elements, and Zr-in-rutile and Ti-in-zircon temperatures. A typical diamond-bearing gneiss records peak conditions of 49 ± 4 kbar and 950–1000 °C. Near isothermal decompression of this rock resulted in the breakdown of phengite associated with a pervasive recrystallization of the rock. The same terrain also contains mica schists that experienced peak conditions close to those of the diamond-bearing rocks, but they were exhumed along a cooler path where phengite remained stable. In these rocks, major and trace element zoning in garnet has been completely equilibrated. A layered gneiss was metamorphosed at UHP conditions in the coesite field, but did not reach diamond-facies conditions (peak conditions: 30 kbar and 800–900 °C). In this sample, garnet records retrograde zonation in major elements and also retains prograde zoning in trace elements. A garnet-kyanite-micaschist that reached significantly lower pressures (24 ± 2 kbar, 710 ± 20 °C) contains garnet with major and trace element zoning. The diverse garnet zoning in samples that experienced different metamorphic conditions allows to establish that diffusional equilibration of rare earth element in garnet likely occurs at ~900–950 °C. Different metamorphic conditions in the four investigated samples are also documented in zircon trace element zonation and mineral inclusions in zircon and monazite. U-Pb geochronology of metamorphic zircon and monazite domains demonstrates that prograde (528–521 Ma), peak (528–522 Ma), and peak to retrograde metamorphism (503–532 Ma) occurred over a relatively short time interval that is indistinguishable from metamorphism of other UHP rocks within the Kokchetav metamorphic belt. Therefore, the assembly of rocks with contrasting P-T trajectories must have occurred in a single subduction-exhumation cycle, providing a snapshot of the thermal structure of a subducted continental margin prior to collision. The rocks were initially buried along a low geothermal gradient. At 20–25 kbar they underwent near isobaric heating of 200 °C, which was followed by continued burial along a low geothermal gradient. Such a step-wise geotherm is in good agreement with predictions from subduction zone thermal models.

Nonlinear tests for genetic studies of complex disease

Linkage and association studies are major analytical tools to search for susceptibility genes for complex diseases. With the availability of large collection of single nucleotide polymorphisms (SNPs) and the rapid progresses for high throughput genotyping technologies, together with the ambitious goals of the International HapMap Project, genetic markers covering the whole genome will be available for genome-wide linkage and association studies. In order not to inflate the type I error rate in performing genome-wide linkage and association studies, multiple adjustment for the significant level for each independent linkage and/or association test is required, and this has led to the suggestion of genome-wide significant cut-off as low as 5 × 10 −7. Almost no linkage and/or association study can meet such a stringent threshold by the standard statistical methods. Developing new statistics with high power is urgently needed to tackle this problem. This dissertation proposes and explores a class of novel test statistics that can be used in both population-based and family-based genetic data by employing a completely new strategy, which uses nonlinear transformation of the sample means to construct test statistics for linkage and association studies. Extensive simulation studies are used to illustrate the properties of the nonlinear test statistics. Power calculations are performed using both analytical and empirical methods. Finally, real data sets are analyzed with the nonlinear test statistics. Results show that the nonlinear test statistics have correct type I error rates, and most of the studied nonlinear test statistics have higher power than the standard chi-square test. This dissertation introduces a new idea to design novel test statistics with high power and might open new ways to mapping susceptibility genes for complex diseases. ^

Identification and functional characterization of novel phosphotyrosine and phosphoserine residues in the interleukin-2 receptor complex

Interleukin-2 (IL-2) is a major T cell growth factor and plays an essential role in the development of normal immune responses. The Janus kinases (Jaks) and Signal transducers and activators of transcription (Stats) are critical for transducing signals from the IL-2 receptors (IL2Rs) to the nucleus to control cell growth and differentiation. In recent years there has been increasing evidence to indicate that the IL-2 activated Jak3/Stat5 pathway provides a new molecular target for immune suppression. Thus, understanding the regulation of this effector cascade has important therapeutic potential.^ One objective of this work was to identify and define the role and molecular mechanism of novel phosphorylation sites in Jak3. Using functional proteomics, three novel Jak3 phosphorylation sites, Y904, Y939 and S574 were identified. Phosphospecific antibodies confirmed that phosphorylation of Y904 and Y939 were mediated by IL-2 and other IL-2 family cytokines in distinct cell types. Biochemical analysis demonstrated that phosphorylation of both Y904 and Y939 positively regulated Jak3 enzymatic activity, while phosphorylation of S574 did not affect Jak3 in vitro kinase activity. However, a gain-of-function mutation of S574 in Jak3 abrogated IL-2 mediated Stat5 activation, suggesting that phosphorylation of this residue might serve a negative role to attenuate IL-2 signaling. Furthermore, mechanistic analysis suggested that phosphorylation of Y904 in Jak3 affects the KmATP of Jak3, while phosphorylation of Y939 in Jak3 was required to bind one of its substrates, Stat5.^ The second objective was to determine the role of serine/threonine phosphatases in the regulation of the IL2R complex. Activation of Jak3 and Stat5 by IL-2 is a transient event mediated by phosphorylation. Using a specific PP1/PP2A inhibitor, we observed that inhibition of PP1/PP2A negatively regulated the IL-2 activated Jak3/Stat5 signaling pathway in a human NK cell line (YT) and primary human T cells. More importantly, coimmunoprecipitation assays indicated that inhibition of PP1/PP2A blocked the formation of an active IL2R complex. Pretreatment of cells with the inhibitor also reduced the electrophoretic mobility of the IL2Rβ and IL2Rγ subunits in YT cells, suggesting that inhibition of PP1/PP2A directly or indirectly regulates undefined serine/threonine kinases which phosphorylate these proteins. Based on these observations, a model has emerged that serine/threonine phosphorylation of the IL2Rβ and IL2Rγ subunits causes a conformational change of these proteins, which disrupts IL2R dimerization and association of Jak3 and Stat5 to these receptors.^

Catchment area of oral cleft cases for two major hospitals in Harris County

Background. Orofacial clefts are among the most common birth defects and considered to be of complex etiology with both genetic and environmental factors.^ Objectives. The purpose of this study was to describe maternal and infant characteristics, examine the catchment area, and determine if there are any geospatial patterns among infants with an orofacial cleft delivered at two major hospitals in Harris County, The Woman's Hospital of Texas and Memorial Hermann Hospital-Texas Medical Center, from January 1, 2003 through December 31, 2007.^ Methods. Data were obtained from two major hospitals in Harris County and included all babies delivered in the period from 2003 through 2007 with an orofacial cleft. Residential addresses were mapped using MapInfo GIS software and the cluster analysis performed with SaTScan software.^ Results. Ninety-nine cases were identified spanning nine counties. 26% of cases resided within a 5-mile radius of the Texas Medical Center. Birth rates ranged from 1.4 to 16.5 per 10,000 total births. A cluster was identified in southwest Harris County, however, it was not significant (p=0.066).^ Conclusion. This study encourages further focus on linking cleft cases to environmental factors in order to determine potential risks. ^

The INO80 chromatin remodeling complex is involved in the nucleotide excision repair pathway

The genomic DNA of eukaryotic cells is well organized into chromatin structures. However, these repressed structures present barriers that block the access of regulatory factors to the genome during various nuclear events. To overcome the obstacle, two major cellular processes, post-modification of histone tails and ATP-dependent chromatin remodeling, are involved in reconfiguring chromatin structure and creating accessible DNA. Despite the current research progress, much remains to be explored concerning the relationship between chromatin remodeling and DNA repair. Recently, one member of the ATP-dependent chromatin remodeling complexes, INO80, has been found to play a crucial role in DNA damage repair. However, the functions of this complex in higher eukaryotes have yet to be determined. The goal of my study is to generate a human somatic INO80 conditional knockout model and investigate the functions of Ino80 in damage repair.^ By homologous targeting of the INO80 locus in human HCT116 colon epithelial cells, I established a human somatic INO80 conditional knockout model. I have demonstrated that the conditional INO80 cells exhibited a sufficiently viable period when the INO80 protein is removed. Moreover, I found that loss of INO80 resulted in deficient UV lesion repair in response to UV while the protein levels of the NER factors such as XPC, XPA, XPD were not affected. And in vitro repair synthesis assay showed that the NER incision and repair synthesis activities were intact in the absence of INO80. Examination on the damage recognition factor XPC showed its recruitment to damage sites was impaired in the INO80 mutant cells. Loss of INO80 also led to reduced enrichment of XPA at the site of UV lesions. Despite the reduced recruitment of XPC and XPA observed in INO80 mutants, no direct interaction was detected. Meanwhile, direct interaction between INO80 and DDB1, the initial UV lesion detector, was detected by coimmunoprecipitation. UV-induced chromosome relaxation was reduced in cells devoid of INO80. These results demonstrate the INO80 complex may participates in the NER by interacting with DDB1 and having a critical role of in creating DNA accessibility for the nucleotide excision pathway. ^

THE NATURAL AND ORTHOGONAL INTERACTION (NOIA) MODELS FOR QUANTITATIVE TRAITS (QTs) AND COMPLEX DISEASES

My dissertation focuses on developing methods for gene-gene/environment interactions and imprinting effect detections for human complex diseases and quantitative traits. It includes three sections: (1) generalizing the Natural and Orthogonal interaction (NOIA) model for the coding technique originally developed for gene-gene (GxG) interaction and also to reduced models; (2) developing a novel statistical approach that allows for modeling gene-environment (GxE) interactions influencing disease risk, and (3) developing a statistical approach for modeling genetic variants displaying parent-of-origin effects (POEs), such as imprinting. In the past decade, genetic researchers have identified a large number of causal variants for human genetic diseases and traits by single-locus analysis, and interaction has now become a hot topic in the effort to search for the complex network between multiple genes or environmental exposures contributing to the outcome. Epistasis, also known as gene-gene interaction is the departure from additive genetic effects from several genes to a trait, which means that the same alleles of one gene could display different genetic effects under different genetic backgrounds. In this study, we propose to implement the NOIA model for association studies along with interaction for human complex traits and diseases. We compare the performance of the new statistical models we developed and the usual functional model by both simulation study and real data analysis. Both simulation and real data analysis revealed higher power of the NOIA GxG interaction model for detecting both main genetic effects and interaction effects. Through application on a melanoma dataset, we confirmed the previously identified significant regions for melanoma risk at 15q13.1, 16q24.3 and 9p21.3. We also identified potential interactions with these significant regions that contribute to melanoma risk. Based on the NOIA model, we developed a novel statistical approach that allows us to model effects from a genetic factor and binary environmental exposure that are jointly influencing disease risk. Both simulation and real data analyses revealed higher power of the NOIA model for detecting both main genetic effects and interaction effects for both quantitative and binary traits. We also found that estimates of the parameters from logistic regression for binary traits are no longer statistically uncorrelated under the alternative model when there is an association. Applying our novel approach to a lung cancer dataset, we confirmed four SNPs in 5p15 and 15q25 region to be significantly associated with lung cancer risk in Caucasians population: rs2736100, rs402710, rs16969968 and rs8034191. We also validated that rs16969968 and rs8034191 in 15q25 region are significantly interacting with smoking in Caucasian population. Our approach identified the potential interactions of SNP rs2256543 in 6p21 with smoking on contributing to lung cancer risk. Genetic imprinting is the most well-known cause for parent-of-origin effect (POE) whereby a gene is differentially expressed depending on the parental origin of the same alleles. Genetic imprinting affects several human disorders, including diabetes, breast cancer, alcoholism, and obesity. This phenomenon has been shown to be important for normal embryonic development in mammals. Traditional association approaches ignore this important genetic phenomenon. In this study, we propose a NOIA framework for a single locus association study that estimates both main allelic effects and POEs. We develop statistical (Stat-POE) and functional (Func-POE) models, and demonstrate conditions for orthogonality of the Stat-POE model. We conducted simulations for both quantitative and qualitative traits to evaluate the performance of the statistical and functional models with different levels of POEs. Our results showed that the newly proposed Stat-POE model, which ensures orthogonality of variance components if Hardy-Weinberg Equilibrium (HWE) or equal minor and major allele frequencies is satisfied, had greater power for detecting the main allelic additive effect than a Func-POE model, which codes according to allelic substitutions, for both quantitative and qualitative traits. The power for detecting the POE was the same for the Stat-POE and Func-POE models under HWE for quantitative traits.

Major and trace element analyses of ODP Leg 120 volcanic rocks (Table 1)

Widespread Lower Cretaceous magmatism occurred along the Indian-Australian/Antarctic margins, and in the juvenile Indian Ocean, during the rifting of eastern Gondwana. The formation of this magmatic province probably began around 120-130 Ma with the eruption of basalts on the Naturaliste Plateau and at Bunbury, western Australia. On the northeast margin of India, activity began around 117 Ma with the Rajmahal continental basalts and associated lamprophyre intrusions. The formation of the Kerguelen Plateau in the Indian Ocean began no later than 114 Ma. Ultramafic lamprophyres (alnoites) were emplaced in the Prince Charles Mountains near the Antarctic continental margin at ~ 110 Ma. These events are considered to be related to a major mantle plume, the remnant of which is situated beneath the region of Kerguelen and Heard islands at the present day. Geochemical data are presented for each of these volcanic suites and are indicative of complex interactions between asthenosphere-derived magmas and the continental lithosphere. Kerguelen Plateau basalts have Sr and Nd isotopic compositions lying outside the field for Indian Ocean mid-ocean ridge basalts (MORB) but, with the exception of Site 738 at the southern end of the plateau, within the range of more recent hotspot basalts from Kerguelen and Heard Islands. However, a number of the plateau tholeiites are characterized by lower 206Pb/204Pb ratios than are basalts from Kerguelen Island, and many also have anomalously high La/Nb ratios. These features suggest that the source of the Kerguelen Plateau basalts suffered contamination by components derived from the Gondwana continental lithosphere. An extreme expression of this lithospheric signature is shown by a tholeiite from Site 738, suggesting that the southernmost part of the Kerguelen Plateau may be underlain by continental crust. The Rajmahal tholeiites mostly fall into two distinct geochemical groups. Some Group I tholeiites have Sr and Nd isotopic compositions and incompatible element abundances, similar to Kerguelen Plateau tholeiites from Sites 749 and 750, indicating that the Kerguelen-Heard mantle plume may have directly furnished Rajmahal volcanism. However, their elevated 207Pb/204Pb ratios indicate that these magmas did not totally escape contamination by continental lithosphere. In contrast to the Group I tholeiites, significant contamination is suggested for Group II Rajmahal tholeiites, on the basis of incompatible element abundances and isotopic compositions. The Naturaliste Plateau and the Bunbury Basalt samples show varying degrees of enrichment in incompatible elements over normal MORB. The Naturaliste Plateau samples (and Bunbury Basalt) have high La/Nb ratios, a feature not inconsistent with the notion that the plateau may consist of stretched continental lithosphere, near the ocean-continent divide.

Major and trace element compositions of the Buendnerschiefer samples

The Bündnerschiefer of the Swiss-Italian Alps is a large sedimentary complex deposited on the Piemonte-Liguria and Valais oceans and associated continental margins from the upper Jurassic to Eocene. It is made of a large variety of sequences associated or not with an ophiolitic basement. The Bündnerschiefer makes an accretionary prism that developed syn-tectonically from the onset of alpine subduction, and it records orogenic metamorphism following episodes of HP metamorphism. The Bündnerschiefer shares important similarities with the Otago schists of New Zealand and with the Wepawaug schists of Connecticut, both of which form accretionary prisms and have an orogenic metamorphic imprint. With the aim of testing the hypothesis of mobility of chemical components as a function of metamorphic grade, in this work I present fifty-five bulk chemical analyses of various lithological facies of the Bündnerschiefer collected along the well-studied field gradient of the Lepontine dome of Central Switzerland, in the Prättigau half window of East Switzerland, and in the Tsaté Nappe of Valle d'Aosta (Italy). The dataset includes the concentration of major components, large ion lithophile elements (Rb, Sr, Ba, Cs), high field strength elements (Zr, Ti, Nb, Th, U, Ta, Hf), fluid-mobile light elements (B, Li), volatiles (CO2, S), REEs, and Y, V, Cr, Co, Sn, Pb, Cu, Zn, Tl, Sb, Be, and Au. These data are compared against the compositions of the global marine sediment reservoir, typical crustal reservoirs, and against the previously measured compositions of Otago and Wepawaug schists. Results reveal that, irrespective of their metamorphic evolution, the bulk chemical compositions of orogenic metasediments are characterized by mostly constant compositional ratios (e.g., K2O/Al2O3, Ba/Al2O3, Sr/CaO, etc.), whose values in most cases are undistinguishable from those of actual marine sediments and other crustal reservoirs. For these rocks, only volatile concentrations decrease dramatically as a function of metamorphic temperature, and significant deviations from the reservoir signatures are evident for SiO2, B, and Li. These results are interpreted as an indication of residual enrichment in the sediments, a process taking place during syn-metamorphic dehydration from the onset of metamorphism in a regime of chemical immobility. Residual enrichment increased the absolute concentrations of the chemical components of these rocks, but did not modify significantly their fundamental ratios. This poor compositional modification of the sediments indicates that orogenic metamorphism in general does not promote significant mass transfer from accretionary prisms. In contrast, mass transfer calculations carried out in a shear zone crosscutting the Bündnerschiefer shows that significant mass transfer occurs within these narrow zones, resulting in gains of H2O, SiO2, Al2O3, K2O, Ba, Y, Rb, Cu, V, Tl, Mo, and Ce during deformation and loss of Na2O, CO2, S, Ni, B, U, and Pb from the rock. These components were presumably transported by an aquo-carbonic fluid along the shear zone. These distinct attitudes to mobilize chemical elements from orogenic sediments may have implications for a potentially large number of geochemical processes in active continental margins, from the recycling of chemical components at plate margins to the genesis of hydrothermal ore deposits.

Geochemistry of the lower sheeted dike complex of ODP Holes 137-504B and 140-504B

Sixty-three samples representing 379 m of sheeted dikes from Deep Sea Drilling Project/Ocean Drilling Program Site 504B have been analyzed for major and selected trace elements by X-ray fluorescence. The samples range from microcrystalline aphyric basalts to moderately phyric (2%-10% phenocrysts) diabase that are typically multiply saturated with plagioclase, olivine, and clinopyroxene, in order of relative abundance. All analyzed samples are classified as Group D compositions with moderate to slightly elevated compatible elements (MgÆ-value = 0.65% ± 0.03%; Al2O3 = 15.5% ± 0.8%; CaO = 13.0% ± 0.3%; Ni = 114 ± 29 ppm), and unusually depleted levels of moderate to highly incompatible elements (Nb < 1 ppm; Zr = 44 ± 7 ppm; Rb < 0.5 ppm; Ba ~ 1 ppm; P2O5 = 0.07% ± 0.02%). These compositions are consistent with a multistage melting of a normal ocean ridge basaltic mantle source followed by extensive fractionation of olivine, plagioclase, and clinopyroxene. Leg 140 aphyric to sparsely phyric (0%-2% phenocrysts) basalts and diabases are compositionally indistinguishable from similarly phyric samples at higher levels in the hole. An examination of the entire crustal section, from the overlying volcanics through the sheeted dikes observed in Leg 140, reveals no significant trends indicating the enrichment or depletion of Costa Rica Rift Zone source magmas over time. Similarly, significant trends toward increased or decreased differentiation cannot be identified, although compositional patterns reflecting variable amounts of phenocryst addition are apparent at various depths. Below ? 1700 mbsf to the bottom of the Leg 140 section, there is a broadly systematic pattern of Zn depletion with depth, the result of high-temperature hydrothermal leaching. This zone of depletion is thought to be a significant source of Zn for the hydrothermal fluids depositing metal sulfides at ridge-crest hydrothermal vents and the sulfide-mineralization zone, located in the transition between pillow lavas and sheeted dikes. Localized zones of intense alteration (60%-95% recrystallization) are present on a centimeter to meter scale in many lithologic units. Within these zones, normally immobile elements Ti, Zr, Y, and rare-earth elements are strongly depleted compared with "fresher" samples centimeters away. The extent of compositional variability of these elements tends to obscure primary igneous trends if the highly altered samples are not identified or removed. At levels up to 40% (or possibly 60%) recrystallization, Ti, Zr, and Y retain their primary signatures. Although the mechanisms are unclear, it is possible that these intense alteration zones are a source of Y and rare-earth elements for the typically rare-earth-element-enriched hydrothermal vent fluids of mid-ocean ridges.

Major oxides, trace elements and rare earth elements of selected basalt samples at DSDP Hole 83-504B

DSDP Hole 504B is the deepest section drilled into oceanic basement, penetrating through a 571.5-m lava pile and a 209-m transition zone of lavas and dikes into 295 m of a sheeted dike complex. To define the basement composition 194 samples of least altered basalts, representing all lithologic units, were analyzed for their major and 26 trace elements. As is evident from the alteration-sensitive indicators H2O+, CO2, S, K, Mn, Zn, Cu, and the iron oxidation ratio, all rocks recovered are chemically altered to some extent. Downhole variation in these parameters enables us to distinguish five depth-related alteration zones that closely correlate with changes in alteration mineralogy. Alteration in the uppermost basement portion is characterized by pronounced K-uptake, sulfur loss, and iron oxidation and clearly demonstrates low-temperature seawater interaction. A very spectacular type of alteration is confined to the depth range from 910 to 1059 m below seafloor (BSF). Rocks from this basement portion exhibit the lowest iron oxidation, the highest H2O+ contents, and a considerable enrichment in Mn, S, Zn, and Cu. At the top of this zone a stockwork-like sulfide mineralization occurs. The chemical data suggest that this basement portion was at one time within a hydrothermal upflow zone. The steep gradient in alteration chemistry above this zone and the ore precipitation are interpreted as the result of mixing of the upflowing hydrothermal fluids with lower-temperature solutions circulating in the lava pile. Despite the chemical alteration the primary composition and variation of the rocks can be reliably established. All data demonstrate that the pillow lavas and the dikes are remarkably uniform and display almost the same range of variation. A general characteristic of the rocks that classify as olivine tholeiites is their high MgO contents (up to 10.5 wt.%) and their low K abundances (-200 ppm). According to their mg-values, which range from 0.60 to 0.74, most basalts appear to have undergone some high-level crystal fractionation. Despite the overall similarity in composition, there are two major basalt groups that have significantly different abundances and ratios of incompatible elements at similar mg-values. The majority of the basalts from the pillow lava and dike sections are chemically closely related, and most probably represent differentiation products of a common parental magma. They are low in Na2O, TiO2, and P2O5, and very low in the more hygromagmaphile elements. Interdigitated with this basalt group is a very rarely occurring basalt that is higher in Na2O, TiO2, P2O5, much less depleted in hygromagmaphile elements, and similar to normal mid-ocean ridge basalt (MORB). The latter is restricted to Lithologic Units 5 and 36 of the pillow lava section and Lithologic Unit 83 of the dike section. The two basalt groups cannot be related by differentiation processes but have to be regarded as products of two different parental magmas. The compositional uniformity of the majority of the basalts suggests that the magma chamber beneath the Costa Rica Rift reached nearly steady-state conditions. However, the presence of lavas and dikes that crystallized from a different parental magma requires the existence of a separate conduit-magma chamber system for these melts. Occasionally mixing between the two magma types appears to have occurred. The chemical characteristics of the two magma types imply some heterogeneity in the mantle source underlying the Costa Rica Rift. The predominant magma type represents an extremely depleted source, whereas the rare magma type presumably originated from regions of less depleted mantle material (relict or affected by metasomatism).