The role of adenosine in pulmonary angiogenesis

Angiogenesis is a feature of chronic lung diseases such as asthma and pulmonary fibrosis; however, the pathways controlling pathological angiogenesis during lung disease are not completely understood. Adenosine is a signaling nucleoside that accumulates as a result of tissue hypoxia and damage. Adenosine has been implicated in the exacerbation of chronic lung disease and in the regulation of angiogenesis; however, the relationship between these factors has not been investigated. The work presented in this dissertation utilized adenosine deaminase (ADA)-deficient mice to determine whether chronic elevations of adenosine in vivo result in pulmonary angiogenesis, and to identify factors that could potentially mediate this process. Results demonstrate that there is substantial angiogenesis in the tracheas of ADA-deficient mice in association with adenosine elevations. Replacement enzyme therapy with pegylated ADA resulted in a lowering of adenosine levels and reversal of tracheal angiogenesis, indicating that the increases in vessel number are dependent on adenosine elevations. Levels of the ELR+ angiogenic chemokine CXCL1 were found to be elevated in an adenosine-dependent manner in the lungs of ADA-deficient mice. Neutralization of CXCL1 and its putative receptor, CXCR2, in ADA-deficient lung lysates resulted in the inhibition of angiogenic activity suggesting that CXCL1 signaling through the CXCR2 receptor is responsible for mediating the observed increases in angiogenesis. Taken together, these findings suggest that adenosine plays an important role, via CXCL1, in the induction of pulmonary angiogenesis and may therefore represent an important therapeutic target for the treatment of pathological angiogenesis. ^

Defining barriers in caring for seriously-ill children in a resource-limited setting: An observational study of 2 children's hospitals in Haiti

Background. According to the WHO 2007 country report, Haiti lags behind the Millennium Development Goal of reducing child mortality and maintains the highest under-5 mortality rate in the Western hemisphere. 3 Overall, few studies exist that seek to better grasp barriers in caring for a seriously ill child in a resource-limited setting and only a handful propose sustainable, effective interventions. ^ Objectives. The objectives of this study are to describe the prevalence of serious illnesses among children hospitalized at 2 children's hospitals in Port au Prince, to determine the barriers faced when caring for seriously ill children, and to report hospital outcomes of children admitted with serious illnesses. ^ Methods. Data were gathered from 2 major children's hospitals in Port au Prince, Haiti (Grace Children's Hospital [GCH] and Hopital d l'Universite d'Etat d'Haiti [HUEH]) using a triangulated approach of focus group discussions, physician questionnaires, and retrospective chart review. 23 pediatric physicians participated in focus group discussions and completed a self-administered questionnaire evaluating healthcare provider knowledge, self-efficacy, and perceived barriers relating to the care of seriously ill children in a resource-limited setting. A sample of 240 patient charts meeting eligibility criteria was abstracted for pertinent elements including sociodemographics, documentation, treatment strategies, and outcomes. Factors associated with mortality were analyzed using χ2 test and Fisher exact test [Minitab v.15]. ^ Results. The most common primary diagnoses at admission were gastroenteritis with moderate dehydration (35.5%), severe malnutrition (25.8%), and pneumonia (19.3%) for GCH, and severe malnutrition (32.6%), sepsis (24.7%), and severe respiratory distress (18%) for HUEH. Overall, 12.9% and 27% of seriously ill patients presented with shock to GCH and HUEH, respectively. ^ Shortage of necessary materials and equipment represented the most commonly reported limitation (18/23 respondents). According to chart data, 9.4% of children presenting with shock did not receive a fluid bolus, and only 8% of patients presenting with altered mental status or seizures received a glucose check. 65% of patients with meningitis did not receive a lumbar puncture due to lack of materials. ^ Hospital mortality rates did not differ by gender or by institution. Children who died were more likely to have a history of prematurity (OR 4.97 [95% CI 1.32-18.80]), an incomplete vaccination record (OR 4.05 [95% CI 1.68-9.74]), or a weight for age ≤3rd percentile (OR 6.1 [95% CI 2.49-14.93]. Case-fatality rates were significantly higher among those who presented with signs of shock compared with those who did not (23.1% vs. 10.7%, RR=2.16, p=0.03). Caregivers did not achieve shock reversal in 21% of patients and did not document shock reversal in 50% of patients. ^ Conclusions. Many challenges face those who seek to optimize care for seriously ill children in resource-limited settings. Specifically, in Haiti, qualitative and quantitative data suggest major issues with lack of supplies, pre-hospital factors, including malnutrition as a comorbidity, and early recognition and management of shock. A tailored intervention designed to address these issues is needed in order to prospectively evaluate improvements in child mortality in a high-risk population.^

The transcriptional repressor Delta EF1 controls resistance to the EGFR inhibitor erlotinib in human HNSCC lines

Epidermal Growth Factor Receptor (EGFR) overexpression occurs in about 90% of Head and Neck Squamous Cell Carcinoma (HNSCC) cases. Aberrant EGFR signaling has been implicated in the malignant features of HNSCC. Thus, EGFR appears to be a logical therapeutic target with increased tumor specificity for the treatment of HNSCC. Erlotinib, a small molecule tyrosine kinase inhibitor, specifically inhibits aberrant EGFR signaling in HNSCC. Only a minority of HNSCC patients were able to derive a substantial clinical benefit from erlotinib. ^ This dissertation identifies Epithelial to Mesenchymal Transition (EMT) as the biological marker that distinguishes EGFR-dependent (erlotinib-sensitive) tumors from the EGFR-independent (erlotinib-resistant) tumors. This will allow us to prospectively identify the patients who are most likely to benefit from EGFR-directed therapy. More importantly, our data identifies the transcriptional repressor DeltaEF1 as the mesenchymal marker that controls EMT phenotype and resistance to erlotinib in human HNSCC lines. si-RNA mediated knockdown of DeltaEF1 in the erlotinib-resistant lines resulted in reversal of the mesenchymal phenotype to an epithelial phenotype and significant increase in sensitivity to erlotinib. ^ DeltaEF1 represses the expression of the epithelial markers by recruiting HDACs to chromatin. This observation allows us to translate our findings into clinical application. To test whether the transcriptional repression by DeltaEF1 underlines the mechanism responsible for erlotinib resistance, erlotinib-resistant lines were treated with an HDAC inhibitor (SAHA) followed by erlotinib. This resulted in a synergistic effect and substantial increase in sensitivity to erlotinib in the resistant cell lines. Thus, combining an HDAC inhibitor with erlotinib represents a novel promising pharmacologic strategy for reversing resistance to erlotinib in HNSCC patients. ^

Mechanism of methylation gene reactivation in human cancer cells

Epigenetic silencing of tumor suppressor genes by DNA hypermethylation at promoter regions is a common event in carcinogenesis and tumor progression. Abrogation of methylation and reversal of epigenetic silencing is a very potent way in cancer treatment. However, the reactivation mechanisms are poorly understood. In this study, we first developed a cell line model system named YB5, derived from SW48 cancer cell line, which bears one copy of stably integrated EGFP gene on Chromosome 1p31.1 region. The GFP gene expression is transcriptionally silenced due to the hypermethylated promoter CMV. However, the GFP expression can be restored using demethylating agent 5-aza-2' deoxycytidine (DAC), and detected by FACS and fluorescent microscopy. Using this system, we observed the heterogeneous reactivation induced by DAC treatment. After flow sorting, GFP negative cells exhibited similar level of incomplete demethylation compared to GFP positive cells on repetitive LINE1 element, tumor suppressor genes such as P16, CDH13, and RASSF1a, and CMV promoter as well. However, the local chromatin of CMV-GFP locus altered to an open structure marked by high H3 lysine 9 acetylation and low H3 lysine 27 tri-methylation in GFP positive cells, while the GFP negative cells retained mostly the original repressive marks. Thus, we concluded that DAC induced DNA hypomethylation alone does not directly determine the level of re-expression, and the resetting of the local chromatin structure under hypomethylation environment is required for gene reactivation. Besides, a lentivirus vector-based shRNA screening was performed using the YB5 system. Although it is the rare chance that vector lands in the neighboring region of GFP, we found that the exogenous vector DNA inserted into the upstream region of GFP gene locus led to the promoter demethylation and reactivated the silenced GFP gene. Thus, epigenetic state can be affected by changing of the adjacent nucleic acid sequences. Further, this hypermethylation silenced system was utilized for epigenetic drug screening. We have found that DAC combined with carboplatin would enhance the GFP% yield and increase expression of other tumor suppressor genes than DAC alone, and this synergistic effect may be related to DNA repair process. In summary, these studies reveal that reversing of methylation silencing requires coordinated alterations of DNA methylation, chromatin structure, and local microenvironment. ^

Growth and development of body fat distribution from skinfold measurements: Longitudinal principal components

Longitudinal principal components analyses on a combination of four subcutaneous skinfolds (biceps, triceps, subscapular and suprailiac) were performed using data from the London Longitudinal Growth Study. The main objectives were to discover at what age during growth sex differences in body fat distribution occur and to see if there is continuity in body fatness and body fat distribution from childhood into the adult status (18 years). The analyses were done for four age sectors (3mon-3yrs, 3yrs-8yrs, 8yrs-18yrs and 3yrs-18yrs). Longitudinal principal component one (LPC1) for each age interval in both sexes represents the population mean fat curve. Component two (LPC2) is a velocity of fatness component. Component three (LPC3) in the 3mon-3yrs age sector represents infant fat wave in both sexes. In the next two age sectors component three in males represents peaks and shifts in fat growth (change in velocity), while in females it represents body fat distribution. Component four (LPC4) in the same two age sectors is a reversal in the sexes of the patterns seen for component three, i.e., in males it is body fat distribution and in females velocity shifts. Components five and above represent more complicated patterns of change (multiple increases and decreases across the age interval). In both sexes there is strong tracking in fatness from middle childhood to adolescence. In males only there is also a low to moderate tracking of infant fat with middle to late childhood fat. These data are strongly supported in the literature. Several factors are known to predict adult fatness among the most important being previous levels of fatness (at earlier ages) and the age at rebound. In addition we found that the velocity of fat change in middle childhood was highly predictive of later fatness (r $\approx -$0.7), even more so than age at rebound (r $\approx -$0.5). In contrast to fatness (LPC1), body fat distribution (LPC3-LPC4) did not track well even though significant components of body fat distribution occur at each age. Tracking of body fat distribution was higher in females than males. Sex differences in body fat distribution are non existent. Some sex differences are evident with the peripheral-to-central ratios after age 14 years. ^

TRPV1 Channels Contribute to Behavioral Hypersensitivity and Spontaneous Activity in Nociceptors After Spinal Cord Injury

A majority of persons who have sustained spinal cord injury (SCI) develop chronic pain. While most investigators have assumed that the critical mechanisms underlying neuropathic pain after SCI are restricted to the central nervous system (CNS), recent studies showed that contusive SCI results in a large increase in spontaneous activity in primary nociceptors, which is correlated significantly with mechanical allodynia and thermal hyperalgesia. Upregulation of ion channel transient receptor vanilloid 1 (TRPV1) has been observed in the dorsal horn of the spinal cord after SCI, and reduction of SCI-induced hyperalgesia by a TRPV1 antagonist has been claimed. However, the possibility that SCI enhances TRPV1 expression and function in nociceptors has not been tested. I produced contusive SCI at thoracic level T10 in adult, male rats and harvested lumbar (L4/L5) dorsal root ganglia (DRG) from sham-treated and SCI rats 3 days and 1 month after injury, as well as from age-matched naive control rats. Whole-cell patch clamp recordings were made from small (soma diameter <30 >μm) DRG neurons 18 hours after dissociation. Capsaicin-induced currents were significantly increased 1 month, but not 3 days, after SCI compared to neurons from control animals. In addition, Ca2+ transients imaged during capsaicin application were significantly greater 1 month after SCI. Western blot experiments indicated that expression of TRPV1 protein in DRG is also increased 1 month after SCI. A major role for TRPV1 channels in pain-related behavior was indicated by the ability of a specific TRPV1 antagonist, AMG9810, to reverse SCI-induced hypersensitivity of hindlimb withdrawal responses to heat and mechanical stimuli. Similar reversal of behavioral hypersensitivity was induced by intrathecal delivery of oligodeoxynucleotides antisense to TRPV1, which knocked down TRPV1 protein and reduced capsaicin-evoked currents. TRPV1 knockdown also decreased the incidence of spontaneous activity in dissociated nociceptors after SCI. Limited activation of TRPV1 was found to induce prolonged repetitive firing without accommodation or desensitization, and this effect was enhanced by SCI. These data suggest that SCI enhances TRPV1 expression and function in primary nociceptors, increasing the excitability and spontaneous activity of these neurons, thus contributing to chronic pain after SCI.

Mechanisms of multidrug resistance: Differences between natural and acquired adriamycin -resistant human colon carcinoma cells

Mechanisms of multidrug resistance (MDR) were studied in two independent MDR sublines (AdR1.2 and SRA1.2) derived from the established human colon carcinoma cell line LoVo. AdR1.2 was developed by long-term continuous exposure of the cells to adriamycin (AdR) in stepwise increments of concentration, while SRA1.2 was selected by repetitive pulse treatments with AdR at a single concentration. In this dissertation, the hypothesis that the mechanism of drug resistance in SRA1.2 is different than that in AdR1.2 is tested. While SRA1.2 demonstrated similar biological characteristics when compared to the parental LoVo, AdR1.2 exhibited remarkable alterations in biological properties. The resistance phenotype of AdR1.2 was reversible when the cells were grown in the drug-free medium whereas SRA1.2 maintained its resistance for at least 10 months under similar conditions. Km and Vmax of carrier-mediated facilitated diffusion AdR transport were similar among the three lines. However, both resistant sublines exhibited an energy-dependent drug efflux. AdR1.2 appeared to possess an activated efflux pump, and a decreased nucleus-binding of AdR, whereas SRA1.2 showed merely a lower affinity in binding of AdR to the nuclei. Southern blot analysis showed no amplification of the MDR1 gene in either of the two resistant subclones. However, Western blot analysis using the C219 monoclonal antibody against P170 glycoprotein detected a Mr 150-kDa plasma protein (P150) in AdR1.2 but not in SRA1.2 or in the parental LoVo. In vitro phosphorylation studies revealed that P150 was a phosphoprotein; its phosphorylation was Mg$\sp{2+}$-dependent and could be enhanced by verapamil, an agent capable of increasing intracellular AdR accumulation in AdR1.2 cells. The phosphorylation studies also revealed elevated phosphorylation of a Mr 66-kDa plasma membrane protein that was detectable in the AdR1.2 revertant and in AdR1.2 when verapamil was present, suggesting that hyperphosphorylation of the Mr 66-kDa protein may be related to the reversal of MDR. SDS-PAGE of the plasma membrane protein demonstrated overproduction of a Mr 130-kDa, MDR-related protein in both the resistant sublines. The Mr 130-kDa, MDR-related protein in both the resistant sublines. The Mr 130-kDa protein was not immunoreactive with C219, but its absence in the AdR1.2 revertant and the parental LoVo suggests that it is an MDR-related plasma membrane protein. In conclusion, the results from this study support the author's hypothesis that the mechanisms responsible for "Acquired" and "Natural" MDR are not identical. ^

Stability and potential application of spliced nuclear pre -mRNA introns

A major portion of this thesis work was dedicated to study the nature and significance of spliced introns. The initial work was focused on studying the IVS1$\sb{\rm C\beta 1}$ intron from a T-cell receptor (TCR)-$\beta$ gene. Compared to an intron lariat control from adenovirus pre-mRNA that was spliced in vitro, IVS1$\sb{\rm C\beta 1}$ was debranched less efficiently by HeLa S100 extracts, although IVS1$\sb{\rm C\beta 1}$ also used the consensus branchpoint in vivo. Subcellular-fractionation analysis showed that most IVS1$\sb{\rm C\beta 1}$ lariats cofractionated with pre-mRNA in the nucleus, consistent with the possibility that intron degradation releases splicing factors which will be available for further rounds of splicing. The half-life of IVS1$\sb{\rm C\beta 1}$ from the endogenous TCR-$\beta$ gene was measured using the general transcription inhibitor actinomycin D to be about $\sim$15 min, which was similar to that of unstable mRNAs such as c-myc mRNA.^ The general transcription inhibitor DRB was also used for intron stability analysis. Unexpectedly, DRB decreased intron and pre-mRNA levels only initially, it later increased the levels of intron-containing RNAs. Inhibition of transcription initiation appeared to be the major early effect (the reduction phase); whereas enhanced premature transcription termination was dominant later (the induction phase).^ Having established the procedures for studying in vivo spliced introns, this approach was applied to study the mechanism of nonsense-mediated downregulation (NMD), a phenomena in which premature termination codons (PTCs) decrease the levels of mRNAs. In this study, the novel intron-oriented approach was applied to study the mechanism of NMD. The levels of spliced introns immediately upstream and downstream of a PTC-bearing exon in a TCR-$\beta$ gene were identified and analyzed along with their pre-mRNA. Although PTC reduced the mRNA levels by 4 to 9 fold, the steady-state levels of spliced introns and the pre-mRNA-to-intron ratios were not significantly altered, indicating that the PTC did not significantly inhibit TCR-$\beta$ RNA splicing. Consistent with this conclusion, the half-lives of the PTC$\sp+$ and PTC$\sp-$ pre-mRNA were similar. The protein synthesis inhibitor cyclohexmide (CHX) upregulated the levels of the PTC$\sp+$ mRNA over 10 fold without affecting the levels of the spliced introns, suggesting that the reversal effect of CHX was through stabilization, not production. These results indicated that inhibition of splicing could not be the major mechanism for the NMD pathway of the TCR-$\beta$ gene, instead, suggesting that mRNA destabilization may be more important. (Abstract shortened by UMI.) ^

Pathways leading to apoptosis resistance in a murine B -cell lymphoma cell system

The aberrant activation of signal transduction pathways has long been linked to uncontrolled cell proliferation and the development of cancer. The activity of one such signaling module, the Mitogen-Activated Protein Kinase (MAPK) pathway, has been implicated in several cancer types including pancreatic, breast, colon, and lymphoid malignancies. Interestingly, the activation of MAP-Kinase-Kinase-Kinase proteins often leads to the additional activation of NF-κB, a transcription factor that acts as a cell survival signal through its control of antiapoptotic genes. We have investigated the role of a specific dimer form of the NF-κB transcription factor family, NF-κB1 (p50) homodimers, in its control of the proto-oncogene, Bcl-2, and we have identified the MEK/ERK (MAPK) signaling cascade as a mediator of NF-κB1 activity. ^ Two murine B cell lymphoma cell lines were used for these studies: LY-as, an apoptosis proficient line with low Bcl-2 protein expression and no nuclear NF-κB activity, and LY-ar, a nonapoptotic line with constitutive p50 homodimer activity and 30 times more Bcl-2 protein expression than LY-as. Experiments modulating p50 activity correlated the activation of p50 homodimers with Bcl-2 expression and additional gel shift experiments demonstrated that the Bcl-2 P1 promoter had NF-κB sites with which recombinant p50 was able to interact. In vitro transcription revealed that p50 enhanced the production of transcripts derived from the Bcl-2 P1 promoter. These data strongly suggest that Bcl-2 is a target gene for p50-mediated transcription and suggest that the activation of p50 homodimers contributes to the expression of Bcl-2 observed in LY-ar cells. ^ Studies of upstream MAPK pathways that could influence NF-κB activity demonstrated that LY-ar cells had phosphorylated ERK proteins while LY-as cells did not. Treatment of LY-ar cells with the MEK inhibitors PD 98059, U0126, and PD 184352 led to a loss of phosphorylated ERK, a reversal of nuclear p50 homodimer DNA binding, and a decrease in the amount of Bcl-2 protein expression. Similarly, the activation of the MEK/ERK pathway in LY-as cells by phorbol ester led to Bcl-2 expression that could be blocked by PD 98059. Furthermore, treatment of LY-ar cells with TNFα, an IKK activator, did not change the suppressive effect of PD 98059 on p50 homodimer activity, suggesting an IKK-independent pathway for p50 homodimer activation. Lastly, all three MEK inhibitors sensitized LY-ar cells to radiation-induced apoptosis. ^ These data indicate that the activation of the MEK/ERK MAP-Kinase signaling pathway acts upstream of p50 homodimer activation and Bcl-2 expression in this B cell lymphoma cell system and suggest that the activation of MEK/ERK may be a key step in the progression of lymphoma to advanced-staged disease. Other researchers have used MEK inhibitors to inhibit cell growth and sensitize a number of tumors to chemotherapies. In light of our data, MEK inhibitors may additionally be useful clinically to radiosensitize cancers of lymphoid origin. ^

Stable oxygen isotope record and Sr/Ca ratios of corals from IODP Holes M0009D and M0023A

We present monthly resolved records of strontium/calcium (Sr/Ca) and oxygen isotope (d18O) ratios from well-preserved fossil corals drilled during the Integrated Ocean Drilling Program (IODP) Expedition 310 'Tahiti Sea Level' and reconstruct sea surface conditions in the central tropical South Pacific Ocean during two time windows of the last deglaciation. The two Tahiti corals examined here are uranium/thorium (U/Th)-dated at 12.4 and 14.2 ka, which correspond to the Younger Dryas (YD) cold reversal and the Bølling-Allerød (B-A) warming of the Northern Hemisphere, respectively. The coral Sr/Ca records indicate that annual average sea surface temperature (SST) was 2.6-3.1 °C lower at 12.4 ka and 1.0-1.6 °C lower at 14.2 ka relative to the present, with no significant changes in the amplitude of the seasonal SST cycle. These cooler conditions were accompanied by seawater d18O (d18Osw) values higher by ~0.8 per mill and ~0.6 per mill relative to the present at 12.4 and 14.2 ka, respectively, implying more saline conditions in the surface waters. Along with previously published coral Sr/Ca records from the island [Cohen and Hart (2004), Deglacial sea surface temperatures of the western tropical Pacific: A new look at old coral. Paleoceanography 19, PA4031, doi:10.1029/2004PA001084], our new Tahiti coral records suggest that a shift toward lower SST by ~1.5 °C occurred from 13.1 to 12.4 ka, which was probably associated with a shift toward higher d18Osw by ~0.2 per mill. Along with a previously published coral Sr/Ca record from Vanuatu [Corrège et al. (2004), Interdecadal variation in the extent of South Pacific tropical waters during the Younger Dyras event. Nature 428, 927-929], the Tahiti coral records provide new evidence for a pronounced cooling of the western to central tropical South Pacific during the Northern Hemisphere YD event.

Carbon and oxygen isotopic compositions of Cibicidoides spp. and fine fraction separates (<10 µm) from ODP Holes 113-689B, 119-738B, and 120-748B

A prominent middle Eocene warming event is identified in Southern Ocean deep-sea cores, indicating that long-term cooling through the middle and late Eocene was not monotonic. At sites on Maud Rise and the Kerguelen Plateau, a distinct negative shift in d18O values (~1.0 per mil) is observed ca. 41.5 Ma. This excursion is interpreted as primarily a temperature signal, with a transient warming of 4°C over 600 k.y. affecting both surface and middle-bathyal deep waters in the Indian-Atlantic region of the Southern Ocean. This isotopic event is designated as the middle Eocene climatic optimum, and is interpreted to represent a significant climatic reversal in the midst of middle to late Eocene deep-sea cooling. The lack of a significant negative carbon isotope excursion, as observed during the Paleocene-Eocene thermal maximum, and the gradual rate of high-latitude warming suggest that this event was not triggered by methane hydrate dissociation. Rather, a transient rise in pCO2 levels is suspected, possibly as a result of metamorphic decarbonation in the Himalayan orogen or increased ridge/arc volcanism during the late middle Eocene.

(Table 1) Remanence properties of samples from ODP Core 126-792A-7H

A combination of high sedimentation rates and high concentrations of magnetic grains in cores from Ocean Drilling Program Leg 126 resulted in the recovery of detailed direction and intensity records of the Brunhes/Matuyama geomagnetic polarity reversal. Virtual geomagnetic poles (VGPs) computed from azimuthally oriented samples taken from the cores of Hole 792A in the western Izu-Bonin forearc basin reveal that the geomagnetic pole persisted at moderate to high southern latitudes for several thousand years before a rapid migration to northern latitudes. Alternating-field demagnetization behavior, as well as NRM, NRM/ARM, and NRM/IRM intensities for samples from this same interval, and the NRM/IRM intensities derived from unoriented core samples from Holes 790C and 791B, drilled in the ~100-km distant Sumisu Rift, all suggest that the dipole field oscillated widely in intensity before the reversal. The fast polarity change occurred at the low point of an ~1100-yr field intensity cycle. This "reversal cycle" immediately followed earlier intensity cycles whose peaks rivaled or surpassed the normalized intensities of discrete samples from well above and below the reversal interval; furthermore, the troughs indicate a much diminished dipole field at their nadir.

(Table 1) Organic geochemistry of ODP Hole 134-832B and Site 134-833

Ocean Drilling Program (ODP) Leg 134 was located in the central part of the New Hebrides Island Arc, in the Southwest Pacific. Here the d'Entrecasteaux Zone of ridges, the North d'Entrecasteaux Ridge and South d'Entrecasteaux Chain, is colliding with the arc. The region has a Neogene history of subduction polarity reversal, ridge-arc collision, and back-arc spreading. The reasons for drilling in this region included the following: (1) to determine the differences in the style and time scale of deformation associated with the two ridge-like features (a fairly continuous ridge and an irregularly topographic seamount chain) that are colliding with the central New Hebrides Island Arc; (2) to document the evolution of the magmatic arc in relation to the collision process and possible Neogene reversal of subduction; and (3) to understand the process of dewatering of a small accretionary wedge associated with ridge collision and subduction. Seven sites were occupied during the leg, five (Sites 827-831) were located in the d'Entrecasteaux Zone where collision is active. Three sites (Sites 827, 828, and 829) were located where the North d'Entrecasteaux Ridge is colliding, whereas two sites (Sites 830 and 831) were located in the South d'Entrecasteaux Chain collision zone. Sites 828 (on North d'Entrecasteaux Ridge) and 831 (on Bougainville Guyot) were located on the Pacific Plate, whereas all other sites were located on a microplate of the North Fiji Basin. Two sites (Sites 832 and 831) were located in the intra-arc North Aoba Basin. Results of Leg 134 drilling showed that forearc deformation associated with the North d'Entrecasteaux Ridge and South d'Entrecasteaux Chain collision is distinct and different. The d'Entrecasteaux Zone is an Eocene subduction/obduction complex with a distinct submerged island arc. Collision and subduction of the North d'Entrecasteaux Ridge results in off scraping of ridge material and plating of the forearc with thrust sheets (flakes) as well as distinct forearc uplift. Some offscraped sedimentary rocks and surficial volcanic basement rocks of the North d'Entrecasteaux Ridge are being underplated to the New Hebrides Island forearc. In contrast, the South d'Entrecasteaux Chain is a serrated feature resulting in intermittent collision and subduction of seamounts. The collision of the Bougainville Guyot has indented the forearc and appears to be causing shortening through thrust faulting. In addition, we found that the Quaternary relative convergence rate between the New Hebrides Island Arc at the latitude of Espiritu Santo Island is as high as 14 to 16 cm/yr. The northward migration rate of the d'Entrecasteaux Zone was found the be ~2 to 4 cm/yr based on the newly determined Quaternary relative convergence rate. Using these rates we established the timing of initial d'Entrecasteaux Zone collision with the arc at ~3 Ma at the latitude of Epi Island and fixed the impact of the North d'Entrecasteaux Ridge upon Espiritu Santo Island at early Pleistocene (between 1.89 and 1.58 Ma). Dewatering is occurring in the North d'Entrecasteaux Ridge accretionary wedge, and the wedge is dryer than other previously studied accretionary wedges, such as Barbados. This could be the result of less sediment being subducted at the New Hebrides compared to the Barbados.

(Table 1) Paleomagnetic of ODP Site 136-842

Paleomagnetic studies on sediments recovered during Leg 136 have yielded a polarity reversal sequence that can be compared with the global magnetic reversal time scale to establish a sedimentation rate for Hole 842B. This sedimentation rate is substantially higher than that normally observed in the central Pacific basin probably as a result of the contribution of volcanic ash to the normal pelagic sources of sediment. The basalt samples from the oceanic crust at Site 843 have been used to determine a paleolatitude of 10.2°S for the 110±2 m.y.-old crust from this site. Detailed studies of the polarity transitions yielded few intermediate directions, but these few records provide support for the "Americas" transitional path observed at other continental and marine sites in Europe and North America.

A low-latitude Upper Pleistocene oxygen isotope stack

Below oxygen isotope stage 16, the orbitally derived time-scale developed by Shackleton et al. (1990) from ODP site 677 in the equatorial Pacific differs significantly from previous ones (e.g. Kominz and Pisias, 1979 doi:10.1126/science.204.4389.171; Morley and Hays, 1981 doi:10.1016/0012-821X(81)90034-0, Imbrie et al. 1984), yielding estimated ages for the last Earth magnetic reversals that are 5-7% older than the K/Ar values (Mankinen and Dalrymple, 1979 doi:10.1029/JB084iB02p00615; Berggren et al., 1985; Harland and Armstrong, 1989) but are in good agreement with recent Ar/Ar dating (Baksi et al., 1991; 1992 doi:10.1126/science.256.5055.356; Spell and McDougall, 1992 doi:10.1029/92GL01125). These results suggest that in the lower Brunhes and upper Matuyama chronozones most deep-sea climatic records retrieved so far apparently missed or misinterpreted several oscillations predicted by the astronomical theory of climate. To test this hypothesis, we studied a high-resolution oxygen isotope record from giant piston core MD900963 (Maldives area, tropical Indian Ocean) in which precession-related oscillations in delta18O are particularly well expressed, owing to the superimposition of a local salinity signal on the global ice volume signal (Rostek et al., 1993 doi:10.1038/364319a0). Three additional precession-related cycles are observed in oxygen isotope stages 17 and 18 of core MD900963, compared to the SPECMAP composite curves (Imbrie et al., 1984; Prell et al., 1986 doi:10.1029/PA001i002p00137), and stage 21 clearly presents three precession oscillations, as predicted by Shackleton et al. (1990). The precession peaks found in the delta18O record from core MD900963 are in excellent agreement with climatic oscillations predicted by the astronomical theory of climate. Our delta18O record therefore permits the development of an accurate astronomical time-scale. Based on our age model, the Brunhes-Matuyama reversal is dated at 775 +/- 10 ka, in good agreement with the age estimate of 780 ka obtained by Shackleton et al. (1990) and recent radiochronological Ar/Ar datings on lavas (Baksi et al., 1991; 1992; Spell and McDougall, 1992). We developed a new low-latitude, Upper Pleistocene delta18O reference record by stacking and tuning the delta18O records from core MD900963 and site 677 to orbital forcing functions.