Effectiveness of therapeutic Salmonella Typhimurium in selectively targeting human cancer cell lines [abstract]

Abstract only availableStudies indicate that non-virulent strains of Salmonella Typhimurium have tumor-targeting activity. Indeed, S. Typhimurium has been observed to selectively target cancer tissue by a ratio of over 1000:1. Most of these studies focused on the cancer cell selectivity of one strain, the genetically modified S. typhimurium VNP20009. One such study found that a single IV injection of VNP20009 produced tumor growth inhibition of 57 - 95% in mice. Another study conducted by Thamm and associates found that administration of VNP20009 results in dectable bacterial colonization of tumor tissue and partial anti-tumor activity in tumor-bearing dogs. Despite its selectivity, VNP20009 was shown to be too toxic when given to patients in phase I clinical tests. Scientists at Columbia's Cancer Research Center developed a therapeutic strain, CRC2636, an archival strain of S. typhimurium that has been shown to destroy PC-3M without extensive lysis of the cancer cells, a factor thought to contribute to the toxicity of VNP20009. Our research strategy involved analyzing the effectiveness of CRC2636 in selectively targeting prostate, breast, and colon cancer cell lines when incubated with their normal counterparts. In order to track CRC2636 in the attachment and invasion studies, we electroporated pRST plasmids that constitutively expressed the fluorescent mCherry protein into our therapeutic strain. Attachment studies were done on a time course from 10 minutes up to 4 hours and invasion studies were done up to 16 hours. Quantitative results were obtained by counting the number of attached bacterial cells to the cancerous and normal cells at the various time points tested.Cancer Research Cente

Genetic characterization of the silkworm Bombyx mori by simple sequence repeat (SSR)-anchored PCR

Thirteen diverse strains of the silkworm Bombyx mori were analysed using the simple sequence repeat anchored polymerase chain reaction (SSR-anchored PCR) or Inter-SSR-PCR (ISSR-PCR). A set of four 5'-anchored and two 3'-anchored repeat primers amplified a total of 239 bands out of which 184 (77%) were polymorphic. The 5'-anchored primers revealed more distinct polymorphic markers than the 3'-anchored primers and the ISSR-PCR method showed greater variability than RAPDs. The strain-specific pattern was shown to be inherited and segregated in a Mendelian fashion. A dendrogram constructed using the UPGMA method revealed two distinct groups, one comprising nondiapausing and one comprising diapausing strains. These results suggest that the ISSR-PCR method is potentially useful for genetic fingerprinting of silkworm genotypes and as a mapping tool in the silkworm

Comparative selectivity of various Salmonella typhimurium strains in targeting prostate cancer cells [abstract]

Abstract only availableRecent studies indicate that non-virulent strains of serovar typhimurium () have tumor-targeting activity. Indeed, S. typhimurium has been observed to selectively target cancer tissue by a ratio of over 1000:1. However, most of these studies focused on the cancer cell selectivity of one strain, the genetically modified VNP20009. One such study found that a single IV injection of VNP20009 produced tumor growth inhibition of 57-95% in mice. Another study conducted by Thamm and associates found that administration of VNP20009 results in detectable bacterial colonization of tumor tissue and partial anti-tumor activity in tumor-bearing dogs. However, VNP20009 was shown to be too toxic when given to cancer patients in phase I clinical tests. Scientists at Columbia's Cancer Research Center discovered an archival strain of (CRC1674) that destroys PC-3M prostate cancer cells without extensive lysis of the cancer cells, a factor thought to contribute to the toxicity of VNP20009. This project studies the comparative selectivity of four strains for prostate cancer cells. In order to study attachment to prostate cancer cells, shorter incubation times were used, up to a period of 4 hours. Invasion assays involved incubation periods up to 24 hours. To confirm distinct selectivity towards prostate cancer cells only, the study also included attachment and invasion assays using noncancerous prostate cells. We have discovered attachment after 5 minutes of co-incubation and are currently investigating long-term effects of co-incubation with prostate cancer and normal cell lines.Life Sciences Undergraduate Research Opportunity Progra

The Kiloparsec-Scale Kinematics of High-Redshift Star-Forming Galaxies

We present the results of a spectroscopic survey of the kinematic structure of star-forming galaxies at redshift z ~ 2 - 3 using Keck/OSIRIS integral field spectroscopy. Our sample is comprised of 12 galaxies between redshifts z ~ 2.0 and 2.5 and one galaxy at z ~ 3.3 which are well detected in either HAlpha or [O III] emission. These observations were obtained in conjunction with the Keck laser guide star adaptive optics system, with a typical angular resolution after spatial smoothing ~ 0.15" (approximately 1 kpc at the redshift of the target sample). At most five of these 13 galaxies have spatially resolved velocity gradients consistent with rotation while the remaining galaxies have relatively featureless or irregular velocity fields. All of our galaxies show local velocity dispersions ~ 60 - 100 km/s, suggesting that (particularly for those galaxies with featureless velocity fields) rotation about a preferred axis may not be the dominant mechanism of physical support. While some galaxies show evidence for major mergers such evidence is unrelated to the kinematics of individual components (one of our strongest merger candidates also exhibits unambiguous rotational structure), refuting a simple bimodal disk/merger classification scheme. We discuss these data in light of complementary surveys and extant UV-IR spectroscopy and photometry, concluding that the dynamical importance of cold gas may be the primary factor governing the observed kinematics of z ~ 2 galaxies. We conclude by speculating on the importance of mechanisms for accreting low angular-momentum gas and the early formation of quasi-spheroidal systems in the young universe.(abridged)Comment: 34 pages, 13 figures. Revised version accepted for publication in the Astrophysical Journal. Version with full-resolution figures is available at http://www.astro.ucla.edu/~drlaw/Papers/OSIRIS_data2.pd

The Physical Nature of Rest-UV Galaxy Morphology During the Peak Epoch of Galaxy Formation

Motivated by the irregular and little-understood morphologies of z ~ 2 - 3 galaxies, we use non-parametric coefficents to quantify the morphologies of 216 galaxies which have been spectroscopically confirmed to lie at redshifts z = 1.8 - 3.4 in the GOODS-N field. Using measurements of ultraviolet (UV) and optical spectral lines, multi-band photometric data, and stellar population models we statistically assess possible correlations between galaxy morphology and physical observables such as stellar mass, star formation rate, and the strength of galaxy-scale outflows. We find evidence that dustier galaxies have more nebulous UV morphologies and that larger, more luminous galaxies may drive stronger outflows, but otherwise conclude that UV morphology is either statistically decoupled from the majority of physical observables or determined by too complex a combination of physical processes to provide characterizations with predictive power. Given the absence of strong correlations between UV morphology and physical parameters such as star formation rates, we are therefore unable to support the hypothesis that morphologically irregular galaxies predominantly represent major galaxy mergers. Comparing galaxy samples, we find that IR-selected BzK galaxies and radio-selected submillimeter galaxies (SMGs) have UV morphologies similar to the optically selected sample, while distant red galaxies (DRGs) are more nebulous.Comment: 26 pages. Accepted for publication in the ApJ. Version with full resolution figures is available at http://www.astro.caltech.edu/~drlaw/Papers/UVmorph.pd

An HST/WFC3-IR Morphological Survey of Galaxies at z = 1.5-3.6: II. The Relation between Morphology and Gas-Phase Kinematics

We analyze rest-frame optical morphologies and gas-phase kinematics as traced by rest-frame far-UV and optical spectra for a sample of 204 star forming galaxies in the redshift range z ~ 2-3 drawn from the Keck Baryonic Structure Survey (KBSS). We find that spectroscopic properties and gas-phase kinematics are closely linked to morphology: compact galaxies with semi-major axis radii r <~ 2 kpc are substantially more likely than their larger counterparts to exhibit LyA in emission. Although LyA emission strength varies widely within galaxies of a given morphological type, all but one of 19 galaxies with LyA equivalent width W_LyA > 20 Angstroms have compact and/or multiple-component morphologies with r <= 2.5 kpc. The velocity structure of absorption lines in the galactic continuum spectra also varies as a function of morphology. Galaxies of all morphological types drive similarly strong outflows (as traced by the blue wing of interstellar absorption line features), but the outflows of larger galaxies are less highly ionized and exhibit larger optical depth at the systemic redshift that may correspond to a decreasing efficiency of feedback in evacuating gas from the galaxy. This v ~ 0 km/s gas is responsible both for shifting the mean absorption line redshift and attenuating W_LyA (via a longer resonant scattering path) in galaxies with larger rest-optical half light radii. In contrast to galaxies at lower redshifts, there is no evidence for a correlation between outflow velocity and inclination, suggesting that outflows from these puffy and irregular systems may be poorly collimated. (Abbrev.)Comment: 18 pages, 11 figures. Revised version accepted for publication in ApJ. Version with full-resolution figures is available at http://di.utoronto.ca/~drlaw/Papers/wfc3_uvspec.pd

Association of trans fatty acids with lipids and other cardiovascular risk factors in an Indian industrial population.

OBJECTIVE: Trans-fat, an invariable component of industrial fat is considered as one of the major dietary factors associated with CVD. Although the use of trans-fat is completely banned in some of the high-income countries where the CVD epidemic is declining, it is widely used in LMIC. We aimed to investigate the association of trans fatty acid in serum with risk markers of CVD in an industrial population in India. Participants were randomly selected from a study conducted in an industrial setting among employees and their family members. Information related to their demographic profile, anthropometric measurements, oil intake were recorded. Fasting samples were collected and stored at - 80 °C for analysis. Their lipid profile and hs CRP were measured and fatty acids analyzed using gas chromatography (GC) with flame ionization detector (FID). RESULTS: Complete data was available for 176 participants. Among trans fatty acids, mono trans fatty acid was significant predictor of serum triglycerides [Unadjusted β (95% CI) 22.9 (2.6, 43.2); Adjusted β (95% CI) 20.4 (3.5, 37.3)]. None of the other trans fatty acids either individually or in group correlated with any of the biochemical markers studied