Plasma homocysteine levels and Alzheimer's Disease: A systematic review

Objective. To systematically review studies published in English on the relationship between plasma total homocysteine (Hcy) levels and the clinical and/or postmortem diagnosis of Alzheimer's disease (AD) in subjects who are over 60 years old.^ Method. Medline, PubMed, PsycINFO and Academic Search Premier, were searched by using the keywords "homocysteine", "Alzheimer disease" and "dementia", and "cognitive disorders". In addition, relevant articles in PubMed using the "related articles" link and by cross-referencing were identified. The study design, study setting and study population, sample size, the diagnostic criteria of the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the Alzheimer's Disease and Related Disorders Association (ADRDA), and description of how Hcy levels were measured or defined had to have been clearly stated. Empirical investigations reporting quantitative data on the epidemiology of the relationship between plasma total Hcy (exposure factor) and AD (outcome) were included in the systematic review.^ Results. A total of 7 studies, which included a total of 2,989 subjects, out of 388 potential articles met the inclusion criteria: four case control and three cohort studies were identified. All 7 studies had association statistics, such as the odds ratio (OR), the relative rates (RR), and the hazard ratio (HR) of AD, examined using multivariate and logistic regression analyses. Three case - comparison studies: Clarke et al. (1998) (OR: 4.5, 95% CI.: 2.2 - 9.2); McIlroy et al. (2002) (OR: 2.9, 95% CI.: 1.00–8.1); Quadri et al. (2004) (OR: 3.7, 95% CI.: 1.1 - 13.1), and two cohort studies: Seshadri et al. (2002) (RR: 1.8, 95% CI.: 1.3 - 2.5); Ravaglia et al. (2005) (HR: 2.1, 95% CI.: 1.7 - 3.8) found a significant association between serum total Hcy and AD. One case-comparison study, Miller et al. (2002) (OR: 2.2, 95% C.I.: 0.3 -16), and one cohort study, Luchsinger et al. (2004) (HR: 1.4, 95% C.I.: 0.7 - 2.3) failed to reject H0.^ Conclusions. The purpose of this review is to provide a thorough analysis of studies that examined the relationship between Hcy levels and AD. Five studies showed a positive statistically significant association between elevated total Hcy values and AD but the association was not statistically significant in two studies. Further research is needed in order to establish evidence of the strong, consistent association between serum total Hcy and AD as well as the presence of the appropriate temporal relationship. To answer these questions, it is important to conduct more prospective studies that examine the occurrence of AD in individuals with and without elevated Hcy values at baseline. In addition, the international standardization of measurements and cut-off points for plasma Hcy levels across laboratories is a critical issue to be addressed for the conduct of future studies on the topic.^

Role of ovarian cancer antigen CA125/MUC16 in development and cancer

Cancer antigen 125 (CA125) is a tumor antigen that is routinely used to monitor the disease progress and the outcome of treatment in ovarian cancer patients. Elevated serum levels of CA125 are detected in over 80% of epithelial ovarian cancer patients. CA125 is a high molecular weight (>1M Dalton) mucin-type glycoprotein encoded by the MUC16 gene on human chromosome 19. Although MUC16 has served as the best serum marker for monitoring growth of ovarian cancer, roles for MUC16 in normal physiology and ovarian cancer are largely unknown. To understand the biological functions of MUC16, I characterized a mouse Muc16 homolog on chromosome 9 by means of expression pattern profiling, phenotype analysis of Muc16 knockout mice, and in vitro and in vivo studies of Muc16 null transformed ovarian surface epithelial (OSE) cells. ^ The mouse Muc16 homolog shares a conserved genomic structure with human MUC16. In addition to being expressed in mouse ovarian cancer, mouse Muc16 mRNA and protein were expressed in the mesothelia covering the heart, lung, ovary, oviduct, spleen, testis, and uterus. The conserved genomic structure and expression pattern of mouse Muc16 to human MUC16 suggests that mouse Muc16 is the ortholog of human MUC16. To understand the biological functions of Muc16, I generated Muc16 knockout mice. Muc16 knockout mice were viable, fertile and normal by one year of age. However, between 18 and 24 months of age, Muc16 knockout mice developed various tissue abnormalities such as ovarian cysts and tumors of the liver and other peritoneal organs. To determine the role of MUC16 in ovarian cancer progression, I established Muc16 null transformed ovarian surface epithelial (OSE) cell lines, following the same method to develop mouse model of epithelial ovarian cancer (Orsulic et al., 2002). Loss of Muc16 did not affect cell morphology, cell proliferation rate, or tumorigenic potential. However, Muc16-null OSE cells showed decreased attachment to extracellular matrix proteins as well as to primary mouse peritoneal mesothelial cells. Peritoneal mesothelia are the most frequent implantation sites of ovarian cancer. Furthermore, a pilot transplantation assay suggests that Muc16 null transformed OSE cells formed less disseminated tumors in the peritoneal cavity compared to wild-type OSE cells. ^ In conclusion, these results demonstrate that MUC16 is not required for normal mouse development or reproduction, but plays important roles in tissue homeostasis, ovarian cancer cell adhesion and dissemination. This study provides the first in vivo evidence of the roles of MUC16 in development, as well as ovarian cancer progression and dissemination. These studies offer valuable insights into possible mechanisms of ovarian cancer development and potential molecular targets for ovarian cancer treatment. ^

Get ur 60: A social marketing campaign to promote and facilitate physical activity among Central Texas middle school students

If allowed to continue unabated, the obesity epidemic may lead to the first decline in life expectancy in the developed world (Olshansky et al., 2005). Similar to the relationship between smoking habits in youth and adulthood, obesogenic dietary and physical activity habits in childhood may persist into adulthood (Kelder et al., 2002). Teaching children how to establish healthy eating habits and activity levels, as well as providing them the necessary resources to internalize and maintain these behaviors, may be the key to curbing this epidemic.^ A school-based obesity prevention approach is advantageous for many reasons including exposure to large captive audiences, reduced costs of sustainability and long-term maintenance, and generalizability of models and results across multiple populations. The effectiveness of school-based programs has been researched over the past 20 years, with promising results.^ Social marketing is a program-planning process that “facilitates the acceptance, rejection, modification, abandonment, or maintenance of particular behaviors” (Grier & Bryant, 2005). Social marketing has been shown to be effective in a variety of public health applications including improving diet, increasing physical activity, and preventing substance abuse. It is hypothesized that social marketing could further enhance the effectiveness of the Coordinated Approach To Child Health (CATCH) Central Texas Middle School Project, a school-based obesity prevention program.^ The development, implementation, and initial evaluation of the get ur 60 campaign, to promote the Center for Disease Control and Prevention (CDC) recommended sixty minutes of daily activity, is described in this paper. Various components of the get ur 60 campaign were assessed to evaluate the effectiveness of the campaign during the first semester of implementation. At the end of the spring semester focus groups were held to collect student reactions to the first semester of the get ur 60 campaign.^ The initial results from the first semester of get ur 60 have demonstrated that the campaign as designed was feasible to implement, accepted at all intervention schools, and resulted in a measure of success. ^

Oceanography during TYDEMAN cruise DCM (DeepChlorMax) to the Equatorial Atlantic

The cruise with RV Tydeman was devoted to study permanently stratified plankton systems in the (sub)tropical ocean, which are characterised by a deep chlorophyll peak between 80 and 150 m. To minimise lateral effects by horizontal transport of nutrients and organic matter from river outflow and upwelling regions, stations were selected in the middle of the North Atlantic Ocean between the continents of America and Africa. (5 - 35° N and 50 - 15° W). Here the vertical distributions of light and nutrients control the abundance and growth of autotrophic algae in the thermically stratified water column. This phytoplankton is numerically dominated by the prokaryotic picoplankters Synechococcus spp. and Prochlorococcus spp., which are smaller than 2 ?m. The productivity of the 100 to 150 m deep euphotic zone can be high, because a high heterotrophic/autotrophic biomass ratio induces a rapid regeneration of nutrients and inorganic carbon. Primary grazers are mainly micro-organisms such as heterotrophic nannoflagellates and ciliates, which feed on the small algae and on bacteria. Heterotrophic bacteria can outnumber the autotrophic algae, because their number is related to the substrate pools of dissolved and particulate dead organic matter. These DOC and detritus pools reach equilibrium at a concentration, where the rate of their production (proportional to algal biomass) equals their mineralisation and sinking rate (proportional to the concentration and weight of POC and detritus). At a relatively low value of the weight-specific loss rates, the equilibrium concentration of these carbon pools and their load of bacteria can be high. The bacterial productivity is proportional to the mineralisation rate, which in a steady state can never be higher than the rate of primary production. Hence the ratio in turnover rate of bacteria and autotrophs tends to be reciprocally proportional to their biomass ratio.

Relative abundance and ranges of selected diatoms from Pliocene-Pleistocene sections of ODP Leg 177, Atlantic sector of the Southern Ocean

During Ocean Drilling Program (ODP) Leg 177, seven sites were drilled aligned on a transect across the Antarctic Circumpolar Current in the Atlantic sector of the Southern Ocean. The primary scientific objective of Leg 177 was the study of the Cenozoic paleoceanographic and paleoclimatic history of the southern high latitudes and its relationship with the Antarctic cryosphere development. Of special emphasis was the recovery of Pliocene-Pleistocene sections, allowing paleoceanographic studies at millennial or higher time resolution, and the establishment of refined biostratigraphic zonations tied to the geomagnetic polarity record and stable isotope records. At most sites, multiple holes were drilled to ensure complete recovery of the section. A description of the recovered sections and the construction of a multihole splice for the establishment of a continuous composite is presented in the Leg 177 Initial Reports volume for each of the sites (Gersonde, Hodell, Blum, et al., 1999). Here we present the relative abundance pattern and the stratigraphic ranges of diatom taxa encountered from shore-based light microscope studies completed on the Pliocene-Pleistocene sequences from six of the drilled sites (Sites 1089-1094). No shore-based diatom studies have been conducted on the Pliocene-Pleistocene sediments obtained at Site 1088, located on the northern crest of the Agulhas Ridge, because of the scattered occurrence and poor preservation of diatoms in these sections (Shipboard Scientific Party, 1999b). The data included in our report present the baseline of a diatom biostratigraphic study of Zielinski and Gersonde (2002), which (1) includes a refinement of the southern high-latitude Pliocene-Pleistocene diatom zonation, in particular for the middle and late Pleistocene, and (2) presents a biostratigraphic framework for the establishment of age models of the recovered sediment sections. Zielinski and Gersonde (2002) correlated the diatom ranges with the geomagnetic polarity record established shipboard (Sites 1090 and 1092) (Shipboard Scientific Party, 1999c, 1999d) and on shore (Sites 1089, 1091, 1093, and 1094) by Channell and Stoner (2002). The Pliocene-Pleistocene diatom zonation proposed by Zielinski and Gersonde (2002) relies on a diatom zonation from Gersonde and Bárcena (1998) for the northern belt of the Southern Ocean. Because of latitudinal differentiation of sea-surface temperature, nutrients, and salinity between Antarctic and Subantarctic/subtropical water masses, the Pliocene-Pleistocene stratigraphic marker diatoms are not uniformly distributed in the Southern Ocean (Fenner, 1991; Gersonde and Bárcena, 1998). As a consequence, Zielinski and Gersonde (2002) propose two diatom zonations for application in the Antarctic Zone south of the Polar Front (Southern Zonation, Sites 1094 and 1093) and the area encompassing the Polar Front Zone (PFZ) and the Subantarctic Zone (Northern Zonation, Sites 1089-1092). This accounts especially for the Pleistocene zonation where Hemidiscus karstenii, whose first abundant occurrence datum and last occurrence datum defines the subzonation of the northern Thalassiosira lentiginosa Zone, occurs only sporadically in the cold-water realm south of the PFZ and thus is not applicable in sections from this area. However, newly established marker species assigned to the genus Rouxia (Rouxia leventerae and Rouxia constricta) are more related to cold-water environments and allow a refinement of the Pleistocene stratigraphic zonation for the southern cold areas. A study relying on quantitative counts of both Rouxia species confirms the utility of these stratigraphic markers for the identification of sequences attributed to marine isotope Stages 6 and 8 in the southern Southern Ocean (Zielinski et al., 2002).

Zircons, isotope ratios and element analyses from tonalite and oxide gabbro of the mid-ocean ridge from ODP Hole 176-735B

A limiting factor in the accuracy and precision of U/Pb zircon dates is accurate correction for initial disequilibrium in the 238U and 235U decay chains. The longest-lived-and therefore most abundant-intermediate daughter product in the 235U isotopic decay chain is 231Pa (T1/2 = 32.71 ka), and the partitioning behavior of Pa in zircon is not well constrained. Here we report high-precision thermal ionization mass spectrometry (TIMS) U-Pb zircon data from two samples from Ocean Drilling Program (ODP) Hole 735B, which show evidence for incorporation of excess 231Pa during zircon crystallization. The most precise analyses from the two samples have consistent Th-corrected 206Pb/238U dates with weighted means of 11.9325 ± 0.0039 Ma (n = 9) and 11.920 ± 0.011 Ma (n = 4), but distinctly older 207Pb/235U dates that vary from 12.330 ± 0.048 Ma to 12.140 ± 0.044 Ma and 12.03 ± 0.24 to 12.40 ± 0.27 Ma, respectively. If the excess 207Pb is due to variable initial excess 231Pa, calculated initial (231Pa)/(235U) activity ratios for the two samples range from 5.6 ± 1.0 to 9.6 ± 1.1 and 3.5 ± 5.2 to 11.4 ± 5.8. The data from the more precisely dated sample yields estimated DPazircon/DUzircon from 2.2-3.8 and 5.6-9.6, assuming (231Pa)/(235U) of the melt equal to the global average of recently erupted mid-ocean ridge basaltic glasses or secular equilibrium, respectively. High precision ID-TIMS analyses from nine additional samples from Hole 735B and nearby Hole 1105A suggest similar partitioning. The lower range of DPazircon/DUzircon is consistent with ion microprobe measurements of 231Pa in zircons from Holocene and Pleistocene rhyolitic eruptions (Schmitt (2007; doi:10.2138/am.2007.2449) and Schmitt (2011; doi:10.1146/annurev-earth-040610-133330)). The data suggest that 231Pa is preferentially incorporated during zircon crystallization over a range of magmatic compositions, and excess initial 231Pa may be more common in zircons than acknowledged. The degree of initial disequilibrium in the 235U decay chain suggested by the data from this study, and other recent high precision datasets, leads to resolvable discordance in high precision dates of Cenozoic to Mesozoic zircons. Minor discordance in zircons of this age may therefore reflect initial excess 231Pa and does not require either inheritance or Pb loss.

Long chain 1,13- and 1,15-diols in surface sediments ans SST reconstruction for sediment core GeoB6518-1

Although commonly reported in marine and freshwater environments, little is known about the biological sources of long chain alkyl 1,13- and 1,15-diols, and factors controlling their distributions. Here we analyzed the occurrence and distribution of these lipids in a comprehensive set of marine surface sediments and compare their distributions with environmental conditions like sea surface temperature (SST), salinity and nutrient concentrations. Fractional abundances of the C28 1,13-, C30 1,13- and C30 1,15-diols show a strong correlation with SST and based on these results, we propose the Long chain Diol Index (LDI), which expresses the C30 1,15-diol abundance relative to those of C28 1,13-, C30 1,13- and C30 1,15-diols. The LDI shows a strong linear correlation with SST (LDI = 0.033 × SST + 0.095; R2 = 0.969, n = 162) over a temperature range of -3 to 27 °C. Long chain diol distributions in sediments from the South Atlantic close to the Congo River outflow (West Africa) provided a 43 kyr LDI SST record. This record reflects several known climatic events and shows similarities with an alkenone-derived SST record obtained using the same suite of sediments, both in trend and in terms of absolute SST. This confirms the potential of the LDI as a proxy for palaeo-SST reconstruction.

Dust record from the EPICA Dome C ice core, Antarctica, covering 0 to 800 kyr BP

Dust can affect the radiative balance of the atmosphere by absorbing or reflecting incoming solar radiation and it can be a source of micronutrients, such as iron, to the ocean. It has been suggested that production, transport, and deposition of dust is influenced by climatic changes on glacial-interglacial timescales. Here we present a high-resolution aeolian dust record from the EPICA Dome C ice core in East Antarctica, which provides an undisturbed climate sequence over the last eight climatic cycles. We find that there is a significant correlation between dust flux and temperature records during glacial periods that is absent during interglacial periods. Our data suggests that dust flux is increasingly correlated with Antarctic temperature as climate becomes colder. We interpret this as progressive coupling of Antarctic and lower latitudes climate. Limited changes in glacial-interglacial atmospheric transport time Mahowald et al. (1999, doi:10.1029/1999JD900084), Jouzel et al. (2007, doi:10.1126/science.1141038), and Werner et al. (2002, doi:10.1029/2002JD002365) suggest that the sources and lifetime of dust are the major factors controlling the high glacial dust input. We propose that the observed ~25-fold increase in glacial dust flux over all eight glacial periods can be attributed to a strengthening of South American dust sources, together with a longer atmospheric dust particle life-time in the upper troposphere resulting from a reduced hydrological cycle during the ice ages.

Major element composition of phenocrysts from the volcanic basement of ODP Hole 125-786B, Izu forearc region, Philippine Sea

Early arc volcanism during Eocene to Oligocene in the Izu forearc region was investigated during ODP Legs 125 and 126 in 1989, and effusive and intrusive volcanics were recovered from Leg 125 Site 786. These rocks were all classified into boninites and associated rocks by Leg 125 Shipboard Scientific Party, and they concluded that boninitic volcanism had occurred before 40 Ma, and arc tholeiitic volcanism began after 40 Ma. In this study, lava flows and breccias that classified into boninite series are divided into two groups, tholeiite and boninite, based on petrographical and petrological properties. Both series are also distinguished by bulk rock composition. It is considered that the sources of both rock types have similar depleted compositions because of their similar, very low bulk HFSE concentrations. We suggest that boninitic and tholeiitic volcanism occurred closely in time and space, and reflected different temperature and water condition.