Dissecting the polar dichotomy of the noncondensable gas enhancement on Mars using the NASA Ames Mars General Circulation Model

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95628/1/jgre2298.pd

Oral tolerance to cancer can be abrogated by T regulatory cell inhibition

Oral administration of tumour cells induces an immune hypo-responsiveness known as oral tolerance. We have previously shown that oral tolerance to a cancer is tumour antigen specific, non-cross-reactive and confers a tumour growth advantage. We investigated the utilisation of regulatory T cell (Treg) depletion on oral tolerance to a cancer and its ability to control tumour growth. Balb/C mice were gavage fed homogenised tumour tissue – JBS fibrosarcoma (to induce oral tolerance to a cancer), or PBS as control. Growth of subcutaneous JBS tumours were measured; splenic tissue excised and flow cytometry used to quantify and compare systemic Tregs and T effector (Teff) cell populations. Prior to and/or following tumour feeding, mice were intraperitoneally administered anti-CD25, to inactivate systemic Tregs, or given isotype antibody as a control. Mice which were orally tolerised prior to subcutaneous tumour induction, displayed significantly higher systemic Treg levels (14% vs 6%) and faster tumour growth rates than controls (p<0.05). Complete regression of tumours were only seen after Treg inactivation and occurred in all groups - this was not inhibited by tumour feeding. The cure rates for Treg inactivation were 60% during tolerisation, 75% during tumour growth and 100% during inactivation for both tolerisation and tumour growth. Depletion of Tregs gave rise to an increased number of Teff cells. Treg depletion post-tolerisation and post-tumour induction led to the complete regression of all tumours on tumour bearing mice. Oral administration of tumour tissue, confers a tumour growth advantage and is accompanied by an increase in systemic Treg levels. The administration of anti-CD25 Ab decreased Treg numbers and caused an increase in Teffs. Most notably Treg cell inhibition overcame established oral tolerance with consequent tumor regression, especially relevant to foregut cancers where oral tolerance is likely to be induced by the shedding of tumour tissue into the gut

The Crystal Structure of the Ribosome Bound to EF-Tu and Aminoacyl-tRNA

The ribosome selects a correct transfer RNA (tRNA) for each amino acid added to the polypeptide chain, as directed by messenger RNA. Aminoacyl-tRNA is delivered to the ribosome by elongation factor Tu (EF-Tu), which hydrolyzes guanosine triphosphate (GTP) and releases tRNA in response to codon recognition. The signaling pathway that leads to GTP hydrolysis upon codon recognition is critical to accurate decoding. Here we present the crystal structure of the ribosome complexed with EF-Tu and aminoacyl-tRNA, refined to 3.6 angstrom resolution. The structure reveals details of the tRNA distortion that allows aminoacyl-tRNA to interact simultaneously with the decoding center of the 30S subunit and EF-Tu at the factor binding site. A series of conformational changes in EF-Tu and aminoacyl-tRNA suggests a communication pathway between the decoding center and the guanosine triphosphatase center of EF-Tu

The Crystal Structure of the Ribosome Bound to EF-Tu and Aminoacyl-tRNA

The ribosome selects a correct transfer RNA (tRNA) for each amino acid added to the polypeptide chain, as directed by messenger RNA. Aminoacyl-tRNA is delivered to the ribosome by elongation factor Tu (EF-Tu), which hydrolyzes guanosine triphosphate (GTP) and releases tRNA in response to codon recognition. The signaling pathway that leads to GTP hydrolysis upon codon recognition is critical to accurate decoding. Here we present the crystal structure of the ribosome complexed with EF-Tu and aminoacyl-tRNA, refined to 3.6 angstrom resolution. The structure reveals details of the tRNA distortion that allows aminoacyl-tRNA to interact simultaneously with the decoding center of the 30S subunit and EF-Tu at the factor binding site. A series of conformational changes in EF-Tu and aminoacyl-tRNA suggests a communication pathway between the decoding center and the guanosine triphosphatase center of EF-Tu

A comparison of particle mass spectrometers during the 1999 Atlanta Supersite Project

During the Atlanta Supersite Project, four particle mass spectrometers were operated together for the first time: NOAA's Particle Analysis by Laser Mass Spectrometer (PALMS), University of California at Riverside's Aerosol Time-of-Flight Mass Spectrometer (ATOFMS), University of Delaware's Rapid Single-Particle Mass Spectrometer II (RSMS-II), and Aerodyne's Aerosol Mass Spectrometer (AMS). Although these mass spectrometers are generally classified as similar instruments, they clearly have different characteristics due to their unique designs. One primary difference is related to the volatilization/ionization method: PALMS, ATOFMS, and RSMS-II utilize laser desorption/ionization, whereas particles in the AMS instrument are volatilized by impaction onto a heated surface with the resulting components ionized by electron impact. Thus mass spectral data from the AMS are representative of the ensemble of particles sampled, and those from the laser-based instruments are representative of individual particles. In addition, the AMS instrument cannot analyze refractory material such as soot, sodium chloride, and crustal elements, and some sulfate or water-rich particles may not always be analyzed with every laser-based instrument. A main difference among the laser-based mass spectrometers is that the RSMS-II instrument can obtain size-resolved single particle composition information for particles with aerodynamic diameters as small as 15 nm. The minimum sizes analyzed by ATOFMS and PALMS are 0.2 and about 0.35 μm, respectively, in aerodynamic diameter. Furthermore, PALMS, ATOFMS, and RSMS-II use different laser ionization conditions. Despite these differences the laser-based instruments found similar individual particle classifications, and their relative fractions among comparable sized particles from Atlanta were broadly consistent. Finally, the AMS measurements of the nitrate/sulfate mole ratio were highly correlated with composite measurements (r^2 = 0.93). In contrast, the PALMS nitrate/sulfate ion ratios were only moderately correlated (r^2 ∼ 0.7)

Distribution of Triatoma dimidiata sensu lato (Reduviidae: Triatominae) and risk factors associated with household invasion in Northern Belize, Central America

To date, Triatoma dimidiata sensu lato [Reduviidae: Triatominae (Latreille 1811)] remains the sole vector species associated with Chagas disease transmission reported from Belize. Human infection data are limited for Belize and the disease transmission dynamics have not been thoroughly investigated, yet the likelihood of autochthonous transmission is supported by the widespread collection of infected vectors from within local households. Here, we report updated infection rates of the vector population and infestation rates for villages in north and central Belize. Overall, 275 households were enrolled in an ongoing vector surveillance program. Of the 41 insects collected, 25 were PCR positive for T. cruzi, indicating an infection rate as high as 60%. To further characterize the epidemiological risk of human-vector contact, determinants of household invasion were modeled. Local households were surveyed and characterized with respect to over 25 key factors that may be associated with household infestation by T. dimidiata s.l. While final models were not strongly predictive with respect to the risk factors that were surveyed, likely due to the low number of collection observations, the presence of domestic/peri-domestic dogs, nearby light sources, and household structure materials could be the focus of continued risk assessments. In northern Belize, this vector survey lends support to T. dimidiata s.l. inhabiting sylvatic settings as opposed to the classical paradigm of domiciliated vector populations. This designation has strong implications for the local level of human exposure risk which can help guide vector surveillance and control resources

ADAM17-dependent proteolysis of L-selectin promotes early clonal expansion of cytotoxic T cells

L-selectin on T-cells is best known as an adhesion molecule that supports recruitment of blood-borne naïve and central memory cells into lymph nodes. Proteolytic shedding of the ectodomain is thought to redirect activated T-cells from lymph nodes to sites of infection. However, we have shown that activated T-cells re-express L-selectin before lymph node egress and use L-selectin to locate to virus-infected tissues. Therefore, we considered other roles for L-selectin proteolysis during T cell activation. In this study, we used T cells expressing cleavable or non-cleavable L-selectin and determined the impact of L-selectin proteolysis on T cell activation in virus-infected mice. We confirm an essential and non-redundant role for ADAM17 in TCR-induced proteolysis of L-selectin in mouse and human T cells and show that L-selectin cleavage does not regulate T cell activation measured by CD69 or TCR internalisation. Following virus infection of mice, L-selectin proteolysis promoted early clonal expansion of cytotoxic T cells resulting in an 8-fold increase over T cells unable to cleave L-selectin. T cells unable to cleave L-selectin showed delayed proliferation in vitro which correlated with lower CD25 expression. Based on these results, we propose that ADAM17-dependent proteolysis of L-selectin should be considered a regulator of T-cell activation at sites of immune activity