Nanoscale petrographic and geochemical insights on the origin of the Palaeoproterozoic stromatolitic phosphorites from Aravalli Supergroup, India.

Stromatolites composed of apatite occur in post-Lomagundi-Jatuli successions (late Palaeoproterozoic) and suggest the emergence of novel types of biomineralization at that time. The microscopic and nanoscopic petrology of organic matter in stromatolitic phosphorites might provide insights into the suite of diagenetic processes that formed these types of stromatolites. Correlated geochemical micro-analyses of the organic matter could also yield molecular, elemental and isotopic compositions and thus insights into the role of specific micro-organisms among these communities. Here, we report on the occurrence of nanoscopic disseminated organic matter in the Palaeoproterozoic stromatolitic phosphorite from the Aravalli Supergroup of north-west India. Organic petrography by micro-Raman and Transmission Electron Microscopy demonstrates syngeneity of the organic matter. Total organic carbon contents of these stromatolitic phosphorite columns are between 0.05 and 3.0 wt% and have a large range of δ(13) Corg values with an average of -18.5‰ (1σ = 4.5‰). δ(15) N values of decarbonated rock powders are between -1.2 and +2.7‰. These isotopic compositions point to the important role of biological N2 -fixation and CO2 -fixation by the pentose phosphate pathway consistent with a population of cyanobacteria. Microscopic spheroidal grains of apatite (MSGA) occur in association with calcite microspar in microbial mats from stromatolite columns and with chert in the core of diagenetic apatite rosettes. Organic matter extracted from the stromatolitic phosphorites contains a range of molecular functional group (e.g. carboxylic acid, alcohol, and aliphatic hydrocarbons) as well as nitrile and nitro groups as determined from C- and N-XANES spectra. The presence of organic nitrogen was independently confirmed by a CN(-) peak detected by ToF-SIMS. Nanoscale petrography and geochemistry allow for a refinement of the formation model for the accretion and phototrophic growth of stromatolites. The original microbial biomass is inferred to have been dominated by cyanobacteria, which might be an important contributor of organic matter in shallow-marine phosphorites.

Variable nutrient stoichiometry (carbon:nitrogen:phosphorus) across trophic levels determines community and ecosystem properties in an oligotrophic mangrove system.

Our study investigated the carbon:nitrogen:phosphorus (C:N:P) stoichiometry of mangrove island of the Mesoamerican Barrier Reef (Twin Cays, Belize). The C:N:P of abiotic and biotic components of this oligotrophic ecosystem was measured and served to build networks of nutrient flows for three distinct mangrove forest zones (tall seaward fringing forest, inland dwarf forests and a transitional zone). Between forest zones, the stoichiometry of primary producers, heterotrophs and abiotic components did not change significantly, but there was a significant difference in C:N:P, and C, N, and P biomass, between the functional groups mangrove trees, other primary producers, heterotrophs, and abiotic components. C:N:P decreased with increasing trophic level. Nutrient recycling in the food webs was highest for P, and high transfer efficiencies between trophic levels of P and N also indicated an overall shortage of these nutrients when compared to C. Heterotrophs were sometimes, but not always, limited by the same nutrient as the primary producers. Mangrove trees and the primary tree consumers were P limited, whereas the invertebrates consuming leaf litter and detritus were N limited. Most compartments were limited by P or N (not by C), and the relative depletion rate of food sources was fastest for P. P transfers thus constituted a bottleneck of nutrient transfer on Twin Cays. This is the first comprehensive ecosystem study of nutrient transfers in a mangrove ecosystem, illustrating some mechanisms (e.g. recycling rates, transfer efficiencies) which oligotrophic systems use in order to build up biomass and food webs spanning various trophic levels.

Ecologically and geologically relevant isotope signatures of C, N, and S: okenone producing purple sulfur bacteria Part I.

Purple sulfur bacteria (PSB) are known to couple the carbon, nitrogen, and sulfur cycling in euxinic environments. This is the first study with multiple strains and species of okenone-producing PSB to examine the carbon (C), nitrogen (N), and sulfur (S) metabolisms and isotopic signatures in controlled laboratory conditions, investigating what isotopic fractionations might be recorded in modern environments and the geologic record. PSB play an integral role in the ecology of euxinic environments and produce the unique molecular fossil okenane, derived from the diagenetic alteration of the carotenoid pigment okenone. Cultures of Marichromatium purpuratum 1591 (Mpurp1591) were observed to have carbon isotope fractionations ((13)ε biomass - CO2), via RuBisCO, ranging from -16.1 to -23.2‰ during exponential and stationary phases of growth. Cultures of Thiocapsa marina 5653 (Tmar5653) and Mpurp1591 had a nitrogen isotope fractionation ((15)ε biomass - NH 4) of -15‰, via glutamate dehydrogenase, measured and recorded for the first time in PSB. The δ(34) SVCDT values and amount of stored elemental sulfur for Mpurp1591 cells grown autotrophically and photoheterotrophically were dependent upon their carbon metabolic pathways. We show that PSB may contribute to the isotopic enrichments observed in modern and ancient anoxic basins. In a photoheterotrophic culture of Mpurp1591 that switched to autotrophy once the organic substrate was consumed, there were bulk biomass δ(13)C values that span a broader range than recorded across the Late Devonian, Permian-Triassic, Triassic-Jurassic, and OAE2 mass extinction boundaries. This finding stresses the complexities in interpreting and assigning δ(13)C values to bulk organic matter preserved in the geologic record.

Pigment production and isotopic fractionations in continuous culture: okenone producing purple sulfur bacteria Part II.

Okenone is a carotenoid pigment unique to certain members of Chromatiaceae, the dominant family of purple sulfur bacteria (PSB) found in euxinic photic zones. Diagenetic alteration of okenone produces okenane, the only recognized molecular fossil unique to PSB. The in vivo concentrations of okenone and bacteriochlorophyll a (Bchl a) on a per cell basis were monitored and quantified as a function of light intensity in continuous cultures of the purple sulfur bacterium Marichromatium purpuratum (Mpurp1591). We show that okenone-producing PSB have constant bacteriochlorophyll to carotenoid ratios in light-harvesting antenna complexes. The in vivo concentrations of Bchl a, 0.151 ± 0.012 fmol cell(-1), and okenone, 0.103 ± 0.012 fmol cell(-1), were not dependent on average light intensity (10-225 Lux) at both steady and non-steady states. This observation revealed that in autotrophic continuous cultures of Mpurp1591, there was a constant ratio for okenone to Bchl a of 1:1.5. Okenone was therefore constitutively produced in planktonic cultures of PSB, regardless of light intensity. This confirms the legitimacy of okenone as a signature for autotrophic planktonic PSB and by extrapolation water column euxinia. We measured the δ(13)C, δ(15)N, and δ(34)S bulk biomass values from cells collected daily and determined the isotopic fractionations of Mpurp1591. There was no statistical relationship in the bulk isotope measurements or stable isotope fractionations to light intensity or cell density under steady and non-steady-state conditions. The carbon isotope fractionation between okenone and Bchl a with respect to overall bulk biomass ((13)ε pigment - biomass) was 2.2 ± 0.4‰ and -4.1 ± 0.9‰, respectively. The carbon isotopic fractionation (13ε pigment-CO2) for the production of pigments in PSB is more variable than previously thought with our reported values for okenone at -15.5 ± 1.2‰ and -21.8 ± 1.7‰ for Bchl a.

Shifts in δ15 N signature following the onset of exogenous feeding in rainbow trout Oncorhynchus mykiss: importance of combining length and age data.

The δ(15) N isotopic change of recently emerged rainbow trout Oncorhynchus mykiss due to diet shift from yolk sac to exogenous feeding was evaluated in a field study. The fit of a general model including both fish length and age in days as co-variables indicates that the specific δ(15) N of individual fish at any given time along the ontogeny is determined by its growth trajectory. The results suggest that estimations based on fish size alone could bias data interpretation and maternal origin determinations in partially migratory salmonids.

Antibody targeting of CD24 efficiently retards growth and influences cytokine milieu in experimental carcinomas.

BACKGROUND: The targeting of cancer stem cells by monoclonal antibodies offers new options for therapy. CD24 is a glycosylphosphatidylinositol-anchored membrane protein with a small protein core and a high level of glycosylation. It is overexpressed in many human carcinomas and is correlated with poor prognosis. CD24 is a marker for pancreatic and ovarian cancer stem cells, whereas breast cancer stem cells are negative for CD24. In cancer cell lines, changes of CD24 expression can alter cellular properties in vitro and tumour growth in vivo. We have shown before that monotherapy with monoclonal antibody (mAb) SWA11 to CD24 effectively retarded tumour growth in xenotransplanted mice. METHODS: Here, we have investigated in more detail the molecular mechanisms of mAb SWA11 therapeutic effects in A549 lung and SKOV3ip ovarian carcinoma models in scid/beige and CD1 mice, respectively. We focused on anti-proliferative, pro-apoptotic, anti-angiogenic and microenvironmental effects of SWA11 mAb treatment. RESULTS: We find that CD24 targeting is associated with changes in tumour cell proliferation and angiogenesis. The treatment lead to increased infiltration of tumour tissues with immune cells suggesting involvement of ADCC. We found that SWA11 mAb treatment strongly altered the intratumoural cytokine microenvironment. The addition of SWA11 mAb to gemcitabine treatment strongly potentiated its anti-cancer efficacy in A549 lung cancer model. CONCLUSION: Our data demonstrate that targeting of CD24 could be beneficial for the anti-cancer treatment combined with standard chemotherapy regimes.

The provenances of asteroids, and their contributions to the volatile inventories of the terrestrial planets.

Determining the source(s) of hydrogen, carbon, and nitrogen accreted by Earth is important for understanding the origins of water and life and for constraining dynamical processes that operated during planet formation. Chondritic meteorites are asteroidal fragments that retain records of the first few million years of solar system history. The deuterium/hydrogen (D/H) values of water in carbonaceous chondrites are distinct from those in comets and Saturn's moon Enceladus, implying that they formed in a different region of the solar system, contrary to predictions of recent dynamical models. The D/H values of water in carbonaceous chondrites also argue against an influx of water ice from the outer solar system, which has been invoked to explain the nonsolar oxygen isotopic composition of the inner solar system. The bulk hydrogen and nitrogen isotopic compositions of CI chondrites suggest that they were the principal source of Earth's volatiles.

A reduced organic carbon component in martian basalts.

The source and nature of carbon on Mars have been a subject of intense speculation. We report the results of confocal Raman imaging spectroscopy on 11 martian meteorites, spanning about 4.2 billion years of martian history. Ten of the meteorites contain abiotic macromolecular carbon (MMC) phases detected in association with small oxide grains included within high-temperature minerals. Polycyclic aromatic hydrocarbons were detected along with MMC phases in Dar al Gani 476. The association of organic carbon within magmatic minerals indicates that martian magmas favored precipitation of reduced carbon species during crystallization. The ubiquitous distribution of abiotic organic carbon in martian igneous rocks is important for understanding the martian carbon cycle and has implications for future missions to detect possible past martian life.

Prognostic significance of L1CAM in ovarian cancer and its role in constitutive NF-κB activation.

BACKGROUND: Overexpression of L1-cell adhesion molecule (L1CAM) has been observed for various carcinomas and correlates with poor prognosis and late-stage disease. In vitro, L1CAM enhances proliferation, cell migration, adhesion and chemoresistance. We tested L1CAM and interleukin-1 beta (IL-1ß) expression in tumor samples and ascitic fluid from ovarian carcinoma patients to examine its role as a prognostic marker. PATIENTS AND METHODS: We investigated tumor samples and ascitic fluid from 232 serous ovarian carcinoma patients for L1CAM by enzyme-linked immunosorbent assay. L1CAM expression was correlated with pathoclinical parameters and patients' outcome. IL-1ß levels were measured in tumor cell lysates. Ovarian cancer cell lines were analyzed for the contribution of L1CAM to IL-1ß production and nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NF-κB) activation. RESULTS: We observed that L1CAM-expressing tumors show a highly invasive phenotype associated with restricted tumor resectability at primary debulking surgery and increased lymphogenic spread. Soluble L1CAM proved to be a marker for poor progression-free survival and chemoresistance. In ovarian carcinoma cell lines, the specific knock-down of L1CAM reduces IL-1ß expression and NF-κB activity. CONCLUSIONS: L1CAM expression contributes to the invasive and metastatic phenotype of serous ovarian carcinoma. L1CAM expression and shedding in the tumor microenvironment could contribute to enhanced invasion and tumor progression through increased IL-1ß production and NF-κB activation.

L1 cell adhesion molecule (L1CAM) as a pathogenetic factor in endometriosis.

BACKGROUND: Endometriosis is a benign and progressive disease with a high prevalence. Women with endometriosis, especially with atypical endometriosis, have a higher probability for developing ovarian cancer compared with women without endometriosis. The L1 cell adhesion molecule (L1CAM) is over expressed in ovarian and endometrial carcinomas and is associated with a bad prognosis. Here, we have analysed L1CAM expression in endometriosis. METHODS AND RESULTS: In our study with the samples from 79 patients with, and 37 patients without, endometriosis, we found that endometriosis cell lines and short-term cultures of endometrium from women with endometriosis expressed L1CAM at the mRNA and protein level. Quantitative RT-PCR analysis showed that L1CAM was expressed at significantly higher level in the epithelial compartment from patients with endometriosis compared with healthy controls (P = 0.0126). By immunohistochemical staining, 15 of 31 ovarian endometriotic lesions (48%) were shown to have L1CAM-positive staining. Of these 15 L1CAM-positive samples, 13 were atypical endometriotic lesions. Soluble L1 present in the conditioned medium of epithelial endometrium cultures from women with endometriosis was able to stimulate neurite outgrowth as measured in a chicken ganglion assay. CONCLUSIONS: We propose that L1CAM could promote endometriosis development by increasing enervation and aggravation. L1CAM expression is higher in atypical endometriosis compared with normal endometriosis.

The cytoplasmic part of L1-CAM controls growth and gene expression in human tumors that is reversed by therapeutic antibodies.

L1 cell adhesion molecule (L1-CAM) is a transmembrane cell adhesion molecule involved in cell migration and axon guidance in the developing nervous system. L1 is also overexpressed in ovarian and endometrial carcinomas and is associated with a bad prognosis. In carcinoma cell lines, L1 overexpression augments cell motility, tumor growth in mice and induces expression of Erk-dependent genes. Here, we show that a mutation in the cytoplasmic portion of L1 (T1247A, S1248A) abrogates Erk activation, blocks cell migration on extracellular matrix proteins and did not augment tumor growth in non-obese diabetic/severe combined immuno-deficient mice. In cells expressing mutant L1, the induction of Erk-dependent genes such as beta3-integrin, cathepsin-B and several transcription factors is eliminated and the invasive phenotype is abrogated. L1 antibodies showed similar effects. They prevented Erk activation and interfered with the Erk-dependent gene expression pattern. These findings provide a rationale for the mode of action of L1 antibodies and suggest that interference with L1 function could become a valuable target for therapy.

The role of L1-CAM immunohistochemial staining in the diagnosis of abdominal-pelvic cancer of uncertain primary site in women.

OBJECTIVE: The L1 adhesion molecule (L1-CAM,CD171) is over expressed in ovarian and endometrial carcinomas and other tumors derived from the Mullerian tract. Here we evaluated whether L1-CAM could serve as a novel tumor marker for the diagnosis of metastatic abdominal-pelvic cancers of uncertain origin in women. PATIENTS AND METHODS: During a 6-year period we investigated 28 patients with metastatic abdominal or pelvic cancer with uncertain primary-origin. In all these cases a thorough clinical, surgical, pathologic and immunohistochemistry evaluation was performed and correlated to the L1-CAM expression as determined by immunohistochemical staining. RESULTS: In 20 patients where the differential diagnosis was primary ovarian or endometrial cancer and primary or recurrent colon cancer, L1 immunohistochemistry staining allowed or supported the correct diagnosis. In four cases L1 staining allowed the correct diagnosis between breast and ovarian cancer. In two cases vaginal metastases of unknown origin were positive to L1 immunohistochemistry staining implying their mullerian origin and one case each of inguinal lymph node metastases and abdominal wall cancer that were positive for L1-CAM, allowed the correct diagnosis of primary ovarian cancer. In a whole, L1-CAM was of crucial role of delinating the final diagnosis in 17 of the 28 cases described. CONCLUSIONS: L1-CAM, a new tumor marker, was found to be specific for metastatic cancer originating from mullerian origin. Its incorporation into the conventional immunohistochemistry analysis in cases of cancer of unknown primary in women, allows a correct diagnosis and subsequent treatment in the majority of cases with abdominal-pelvic carcinomatosis.

CD24 is a marker of exosomes secreted into urine and amniotic fluid.

Exosomes are small membrane vesicles that are secreted from a variety of cell types into various body fluids including the blood and urine. These vesicles are thought to play a role in cell-cell interactions. CD24 is a small but extensively glycosylated protein linked to the cell surface by means of a glycosyl-phosphatidylinositol anchor. In this study we found that CD24 is present in membrane vesicles characterized as exosomes that were isolated from the urine of normal individuals. CD24 was expressed by both tubule cells and podocytes and treatment of the latter with a cholesterol-extracting agent, but not with a calcium ionophore, caused the release of CD24-containing exosomes. Using CD24 as a marker, we found exosomes in the urine of newborn infants and in the amniotic fluid of pregnant women with similar findings made in mice. Interestingly, studies with CD24 knockout mice showed that the exosomes are released from the fetus but not from the mother; however, exosome release was similar from both the knockout and the wild-type mice. This indicates that CD24 is not essential for exosome formation or release but may be a convenient exosome marker. Our studies suggest that exosomal secretion from the embryonic kidney could play a biological role at the fetal-maternal interphase.

Is routine cardiac catheterization necessary in the management of patients with single ventricles across staged Fontan reconstruction? No!

With the advent of cardiac magnetic resonance imaging and high-resolution echocardiography, cardiac catheterization is unnecessary in clinical protocols in the "routine" single ventricle patient. Catheterization adds little to clinical care in these cases, and there are significant risks and costs associated with it. Catheterization should be reserved for cases in which noninvasive evaluations are equivocal, conflictory, demonstrate deterioration, or needed for intervention. This article delineates the role of noninvasive evaluations relative to cardiac catheterization in the routine single ventricle patient.

The role of L1 in the progression of ovarian carcinomas.

The L1 molecule has recently emerged as a promising new biomarker for the prognosis of human ovarian and endometrial tumors. It was initially described as an adhesion molecule for the development of the nervous system but its function in tumor cells is not well known. In this article we summarize recent data on the role of L1 in promoting tumor cell adhesion and migration and in gene regulation. We address the question how L1 determination in tumor tissue samples and in serum and ascites could potentially improve the disease management.

Vascular rings and their effect on tracheal geometry.

The major clinical impact of vascular rings in children is tracheal compression, which presents with recurrent symptoms of stridor, noisy breathing, and wheezing. This study tests the hypothesis that symptomatic patients have altered tracheal geometry compared to nonsymptomatic individuals. We retrospectively reviewed the tracheal dimensions (area and longest and shortest diameters) as visualized by magnetic resonance imaging from the cupola of the lung to the carina of 49 patients referred for evaluation of a vascular ring. The smallest dimension relative to the largest dimension (% of maximum) and the coefficient of variation (CoVar; standard deviation/mean) were assessed for each parameter. In all parameters measured (area and longest and shortest diameters), patients with symptoms due to vascular rings had significantly different values than patients without symptoms. The % of maximum was significantly smaller (area, 48.6 vs 62.1%; longest diameter, 41.0 vs 54.0%; shortest diameter, 45.0 vs 56.5%) and the CoVar was significantly greater (area, 0.26 vs 0.18; longest diameter, 0.31 vs 0.22; shortest diameter, 0.28 vs 0.19) in symptomatic individuals than in nonsymptomatic individuals. Patients with vascular rings who are symptomatic have significantly altered tracheal geometry compared to nonsymptomatic individuals. Magnetic resonance imaging is a useful tool for visualizing both the cardiovascular and the tracheal anatomy in patients with vascular rings and provides useful information for the management and care of these patients.

[The relationship between osteoporosis, osteopenia and periodontitis].

A review of the literature on the reciprocal influence of osteoporosis and periodontitis. The imbalance in coupling of bone remodeling causes skeletal osteopenia and osteoporosis. Does the remodeling imbalance influence the oral bone? Both diseases are chronic, multifactorial and result at bone loss. In addition, the diseases share common risk factors such genetics, dietary, environmental and systemic factors. Different studies indicate that the skeletal bone loss in osteoporosis accelerate the decrease in bone density in oral bone. Although the differences in etiology between the two diseases some studies showed that treatment of osteoporosis improved the periodontal health. Further investigation of the mechanisms behind the relationship between osteoporosis and periodontitis may lead to common treatment strategies.

Noninvasive imaging of isolated persistent fifth aortic arch.

Persistent fifth aortic arch was suspected by echocardiography and confirmed by magnetic resonance imaging (MRI) in an infant with a heart murmur. Selected images including three dimensional reconstruction from MRI demonstrating this very rare congenital anomaly are presented.

A simplified approach for assessment of intracardiac baffles and extracardiac conduits in congenital heart surgery with two- and three-dimensional magnetic resonance imaging.

BACKGROUND: Intracardiac baffles and extracardiac conduits have been used in the reconstructive surgery of a broad spectrum of congenital cardiac malformations. Periodic evaluation of these structures may not lend itself readily to echocardiographic and angiographic imaging. The purpose of the study was to describe the experience of our institution with the use of magnetic resonance imaging (MRI) in evaluating conduits and baffles and to describe the simplified approach we developed to image these structures, which allows for grouping individual lesions into broad categories. METHODS AND RESULTS: We retrospectively reviewed our MRI experience in visualizing these structures from 1989-1996. One hundred thirty-nine patients underwent MRI to visualize 144 structures (116 baffles, 28 conduits). The 116 baffles included 86 Fontan, 16 Mustard, 6 Senning, 6 left ventricle to aorta, 1 right ventricle to aorta, and 1 pulmonary vein to left atrium baffle. The 28 conduits included 15 right ventricle to pulmonary artery, 4 left ventricular apical to aorta, 2 left ventricle to pulmonary artery, 3 aorta to aorta, 2 inferior vena cava to left atrium conduits, and 2 aortic root replacements. Of the 3 aortic-aortic conduits, 1 was in conjoined twins. Both inferior vena cava-left atrial conduits were in a Baffes procedure. An infectious mass missed by echocardiography in a right ventricle to pulmonary artery conduit was visualized by MRI. With multiplanar reconstruction, contiguous images were stacked atop each other and resliced to define the salient points of the anatomy. Three-dimensional reconstruction further added to this delineation. All structures were visualized successfully, and an assessment of obstruction was made. Multiple examples of conduit and baffle narrowing were diagnosed by spin echo and cine MRI and were subsequently confirmed by catheterization and surgical inspection. CONCLUSION: MRI, with multiplanar and 3-dimensional reconstruction, is useful in examining the variety of baffles and conduits used in congenital heart surgery. MRI can add to the care of patients whose echocardiographic windows or whose angiographically overlapping structures do not allow adequate delineation of conduits and baffles.

Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins.

The L1 adhesion molecule plays an important role in axon guidance and cell migration in the nervous system. L1 is also expressed by many human carcinomas. In addition to cell surface expression, the L1 ectodomain can be released by a metalloproteinase, but the biological function of this process is unknown. Here we demonstrate that membrane-proximal cleavage of L1 can be detected in tumors and in the developing mouse brain. The shedding of L1 involved a disintegrin and metalloproteinase (ADAM)10, as transfection with dominant-negative ADAM10 completely abolishes L1 release. L1-transfected CHO cells (L1-CHO) showed enhanced haptotactic migration on fibronectin and laminin, which was blocked by antibodies to alpha v beta 5 and L1. Migration of L1-CHO cells, but not the basal migration of CHO cells, was blocked by a metalloproteinase inhibitor, indicating a role for L1 shedding in the migration process. CHO and metalloproteinase-inhibited L1-CHO cells were stimulated to migrate by soluble L1-Fc protein. The induction of migration was blocked by alpha v beta 5-specific antibodies and required Arg-Gly-Asp sites in L1. A 150-kD L1 fragment released by plasmin could also stimulate CHO cell migration. We propose that ectodomain-released L1 promotes migration by autocrine/paracrine stimulation via alpha v beta 5. This regulatory loop could be relevant for migratory processes under physiological and pathophysiological conditions.