Characterization of an ovarian cancer activating factor in ascites from ovarian cancer patients

Ascites from ovarian cancer patients contain potent growth-promoting activity toward human ovarian cancer cells both in vitro and in vivo. This activity is associated with rapid increases in cytosolic free calcium ([Ca2+]i) as a consequence of phosphoinositide hydrolysis. In this study, we describe the purification, characterization, and identification of an ovarian cancer activating factor (OCAF) from ascites of ovarian cancer patients. We have isolated OCAF by a combination of solvent extraction, silica gel chromatography, and TLC. Mass spectral analysis, phospholipase sensitivity, and gas chromatographic behavior of purified OCAF indicate that OCAF is composed of various species of lysophosphatidic acid (LPA), including LPAs with polyunsaturated fatty acyl chains (linoleic, arachidonic, and docosahexaenoic acids). However, OCAF is more potent than sn-1 palmitoyl, oleoyl, or stearoyl LPA in increasing [Ca2+]i in ovarian cancer cells. The ability of OCAF to alter [Ca2+]i is sensitive to the effects of lipoxidase, whereas the activity of sn-1 oleoyl, stearoyl, or palmitoyl LPA is not, suggesting that polyunsaturated bonds in the fatty acyl chain of OCAF may account for its increased ability to activate ovarian cancer cells. Furthermore, a sn-2 linoleoyl LPA generated by phospholipase A1 treatment of synthetic phosphatidic acid is much more active than are sn-1 palmitoyl, stearoyl, or oleoyl LPA in increasing [Ca2+]i in ovarian cancer cells. Taken together, these data suggest that the ability of OCAF to increase cellular calcium may reside in the structure and/or location of the fatty acyl chain of LPA. Purified OCAF, at concentrations similar to those present in ascites from ovarian cancer patients, was sufficient to induce proliferation of ovarian cancer cells, as indicated by thymidine incorporation, reduction of 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, or colony formation. However, even at optimal concentrations of OCAF, proliferation was lower than that induced by FCS or ascites from ovarian cancer patients, indicating that, although OCAF may be a major regulator of ovarian cancer cells in vivo, it is not the sole mediator present in ascites, and it likely functions in concert with other growth factor activities.     

Whose responsibility is IT (information technology) management?

Line managers are increasingly assuming responsibility for planning, building, and running information systems that affect their operations. This is forcing organizations to evaluate how they allocate IT decision-making responsibilities. This paper describes a conceptual framework and an intervention process that can help firms devise and implement an effective IT management architecture. The authors illustrate their methods with real world examples.     

Radiance-irradiance inversion algorithm for estimating the absorption and backscattering coefficients of natural waters: vertically stratified water bodies

A full multiple-scattering algorithm for inverting profiles of the upwelling and downwelling irradiances to yield profiles of the absorption and backscattering coefficients in a vertically stratified water body is described and tested with simulated data. The algorithm does not require knowledge of the scattering phase function of the medium. The results are better the closer the phase function assumed in the retrievals is to the true phase function, although excellent retrievals of the absorption coefficient can still be obtained with an inaccurate phase function. Simulations show that the algorithm is capable of determining the vertical structure of a stratified water body and usually provides the absorption coefficient profile with an error ?2% and the backscattering coefficient profile with an error ?10%, as long as the spacing between pseudodata samples is sufficiently small that the necessary derivatives of the irradiances can be accurately computed. The performance is only slightly degraded when the upwelling radiance (nadir viewing) is substituted for the upwelling irradiance.     

Recipes for Spatial Statistics with Global Datasets: A Martian Case Study

The Mars Odyssey Gamma Ray Spectrometer has yielded planetary data of global extent. Such remote-sensing missions usually assign the value of a continuous-valued geospatial attribute to a uniform latitude-longitude grid of bins. Typical attributes include elemental-mass fraction, areal fraction of a mineral type, areal fraction of rocks, thermal inertia, etc. The fineness of the grid is chosen according to the spatial resolution of the orbiter and concomitant data processing. We describe methods to maximize the information extracted from both bin and regional data. Rigorous use of statistical parameters and related methods for inter- and intra- regional comparisons are also discussed. While we discuss results from the Mars Odyssey mission, the techniques we describe are applicable whenever continuous-valued attributes of a planet’s surface are characterized with bins and regions. Our goal is to distill the simplest statistical methods for regional comparisons that would be intuitively accessible to planetary scientists.     

Improving sequencing by tunneling with multiplexing and cross-correlations

Sequencing by tunneling is a next-generation approach to read single-base information using electronic tunneling transverse to the single-stranded DNA (ssDNA) backbone while the latter is translocated through a narrow channel. The original idea considered a single pair of electrodes to read out the current and distinguish the bases [1, 2]. Here, we propose an improvement to the original sequencing by tunneling method, in which \(N\) pairs of electrodes are built in series along a synthetic nanochannel. While the ssDNA is forced through the channel using a longitudinal field it passes by each pair of electrodes for long enough time to gather a minimum of \(m\) tunneling current measurements, where \(m\) is determined by the level of sequencing error desired. Each current time series for each nucleobase is then cross-correlated together, from which the DNA bases can be distinguished. We show using random sampling of data from classical molecular dynamics, that indeed the sequencing error is significantly reduced as the number of pairs of electrodes, \(N\) , increases. Compared to the sequencing ability of a single pair of electrodes, cross-correlating \(N\) pairs of electrodes exponentially improves this sequencing ability due to the approximate log-normal nature of the tunneling current probability distributions. We have also used the Fenton–Wilkinson approximation to analytically describe the mean and variance of the cross-correlations that are used to distinguish the DNA bases. The method we suggest is particularly useful when the measurement bandwidth is limited, allowing a smaller electrode gap residence time while still promising to consistently identify the DNA bases correctly.     

Discussion: Competing theories of receptor excitation.

This discussion is mainly an examination of a theoretical idea suggested by Enoch and McConnell. They suggest that a single photoreceptor may be able to respond so that the output of the receptor is "tagged" according to the wavelength of the quantum absorbed. This idea stands contrary to the classical trichromatic scheme, according to which the probability of quantum absorption depends upon the energy of the incident quantum (inversely related to wavelength), but where once a quantum is absorbed all information pertaining to the wavelength associated with that quantum is forever lost. The trichromatic scheme is reviewed, together with the evidence which supports it. Difficulties raised by some of the suggestions of Enoch and McConnell are then evaluated in this context. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dendritic cell-based immunotherapy of prostate cancer

The protective effect of catechins, major components of green tea, was studied in cultured human umbilical vein endothelial cells exposed to toxicity induced by linoleic acid hydroperoxide (LOOH). In the case where cells were incubated in medium containing both LOOH and catechins, (+)-catechin (C) was effective in suppressing of LOOH-induced cytotoxicity, but (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin gallate (EGCG) had no effect. EGCG monoglucoside (EGCG-G1) and EGCG diglucoside (EGCG-G2), apophilic derivatives of EGCG, show a protective effect on LOOH-induced cytotoxicity when present at the time of treatment with LOOH. On the other hand, when cells were incubated with catechins for 24 h before treatment with LOOH there was no protection against the oxidative damage by LOOH. Furthermore, the interaction between catechins and alpha-tocopherol was examined under these culture conditions. C showed a synergistic effect with alpha-tocopherol in protecting against LOOH-induced damage. These results suggest that catechins interact with LOOH present in the medium or near the surface of membranes, but not with LOOH incorporated into cellular membranes and that catechins are able to interact with alpha-tocopherol to provide synergistic protection against the cytotoxicity of LOOH.     

Quantifying the efficiency and biases of forest Saccharomyces sampling strategies

Saccharomyces yeasts are emerging as model organisms for ecology and evolution, and researchers need environmental Saccharomyces isolates to test ecological and evolutionary hypotheses. However, methods for isolating Saccharomyces from nature have not been standardized, and isolation methods may influence the genotypes and phenotypes of studied strains. We compared the effectiveness and potential biases of an established enrichment culturing method against a newly developed direct plating method for isolating forest floor Saccharomyces spp. In a European forest, enrichment culturing was both less successful at isolating Saccharomyces paradoxus per sample collected and less labour intensive per isolated S. paradoxus colony than direct isolation. The two methods sampled similar S. paradoxus diversity: The number of unique genotypes sampled (i.e., genotypic diversity) per S. paradoxus isolate and average growth rates of S. paradoxus isolates did not differ between the two methods, and growth rate variances (i.e., phenotypic diversity) only differed in one of three tested environments. However, enrichment culturing did detect rare Saccharomyces cerevisiae in the forest habitat and also found two S. paradoxus isolates with outlier phenotypes. Our results validate the historically common method of using enrichment culturing to isolate representative collections of environmental Saccharomyces. We recommend that researchers choose a Saccharomyces sampling method based on resources available for sampling and isolate screening. Researchers interested in discovering new Saccharomyces phenotypes or rare Saccharomyces species from natural environments may also have more success using enrichment culturing. We include step-by-step sampling protocols in the supplemental materials.