Steric Shielding of Surface Epitopes and Impaired Immune Recognition Induced by the Ebola Virus Glycoprotein

Many viruses alter expression of proteins on the surface of infected cells including molecules important for immune recognition, such as the major histocompatibility complex (MHC) class I and II molecules. Virus-induced downregulation of surface proteins has been observed to occur by a variety of mechanisms including impaired transcription, blocks to synthesis, and increased turnover. Viral infection or transient expression of the Ebola virus (EBOV) glycoprotein (GP) was previously shown to result in loss of staining of various host cell surface proteins including MHC1 and β1 integrin; however, the mechanism responsible for this effect has not been delineated. In the present study we demonstrate that EBOV GP does not decrease surface levels of β1 integrin or MHC1, but rather impedes recognition by steric occlusion of these proteins on the cell surface. Furthermore, steric occlusion also occurs for epitopes on the EBOV glycoprotein itself. The occluded epitopes in host proteins and EBOV GP can be revealed by removal of the surface subunit of GP or by removal of surface N- and O- linked glycans, resulting in increased surface staining by flow cytometry. Importantly, expression of EBOV GP impairs CD8 T-cell recognition of MHC1 on antigen presenting cells. Glycan-mediated steric shielding of host cell surface proteins by EBOV GP represents a novel mechanism for a virus to affect host cell function, thereby escaping immune detection

Mortality and immortality : the Nobel Prize as an experiment into the effect of status upon longevity

It has been known for centuries that the rich and famous have longer lives than the poor and ordinary. Causality, however, remains trenchantly debated. The ideal experiment would be one in which extra status could somehow be dropped upon a sub-sample of individuals while those in a control group of comparable individuals received none. This paper attempts to formulate a test in that spirit. It collects 19th-century birth data on science Nobel Prize winners. Correcting for potential biases, we estimate that winning the Prize, compared to merely being nominated, is associated with between 1 and 2 years of extra longevity

Improved Expansion and In Vivo Function of Patient T Cells by a Serum-free Medium

Improvements to T cell culture systems that promote long-term engraftment and function of adoptively transferred T cells will likely result in superior clinical benefit to more individuals. To this end, we recently developed a chemically defined cell culture medium that robustly expands all T cell subsets in the absence of human serum. Using a humanized mouse model, we observed that T cells expanded in the absence of human serum provided durable control of tumors, whereas T cells expanded in medium supplemented with human serum only mediated transient control of tumor growth. Importantly, our new medium effectively expanded more differentiated T cells from multiple myeloma patients in the absence of serum. These patient-derived T cells were also able to provide durable control of B cell tumors in vivo, and this long-term control of cancer was lost when T cells were expanded in the presence of serum. Thus, engineered T cells expanded in an optimized medium in the absence of serum may have improved therapeutic potential

The influence of a hydraulic prosthetic ankle on residual limb loading during sloped walking

<div><p>In recent years, numerous prosthetic ankle-foot devices have been developed to address the demands of sloped walking for individuals with lower-limb amputation. The goal of this study was to compare the performance of a passive, hydraulic ankle-foot prosthesis to two related, non-hydraulic ankles based on their ability to minimize the socket reaction moments of individuals with transtibial amputation during a range of sloped walking tasks. After a two-week accommodation period, kinematic data were collected on seven subjects with a transtibial amputation walking on an instrumented treadmill set at various slopes. Overall, this study was unable to find significant differences in the torque at the distal end of the prosthetic socket between an ankle-foot prosthesis with a hydraulic range-of-motion and other related ankle-foot prosthesis designs (rigid ankle, multiaxial ankle) during the single-support phase of walking. In addition, socket comfort and perceived exertion were not significantly different for any of the ankle-foot prostheses tested in this study. These results suggest the need for further work to determine if more advanced designs (e.g., those with microprocessor control of hydraulic features, powered ankle-foot designs) can provide more biomimetic function to prosthesis users.</p></div

Mean socket comfort score (+ 1 standard deviation) across sloped walking conditions (RIGID = light gray, MULTI = gray, HYDRA = black).

<p>This 11-point scale ranges from 0 (worst comfort imaginable) to 10 (greatest comfort imaginable).</p

Demographic data of subjects with unilateral transtibial amputation.

<p>Demographic data of subjects with unilateral transtibial amputation.</p

(A) Minimum and (B) maximum SVA (+ 1 standard deviation) during single-limb support (control = white, RIGID = light gray, MULTI = gray, HYDRA = black).

<p>Positive angles correspond to a reclined shank posture (i.e., the posture that would be expected at initial contact). An asterisk (*) indicates a statistically significant within-group difference (p<0.05) between level and the sloped walking condition across all prosthetic feet.</p

Mean rating of perceived exertion (+ 1 standard deviation) across sloped walking conditions (control = white, RIGID = light gray, MULTI = gray, HYDRA = black).

<p>This scale allows subjects to rate their level of effort from 0 (no exertion) to 10 (maximum possible exertion). An asterisk (*) indicates a statistically significant within-group difference (p<0.05) between level and the sloped walking condition across all prosthetic feet.</p

Mean socket reaction moments of subjects with transtibial amputation (n = 7) during single-limb support for the following sloped walking conditions: (A) 10° decline, (B) level, and (C) 10° incline.

<p>Dashed band corresponds to the mean reaction moment (± 1 standard deviation) of an able-bodied control group (n = 7) at a shank location equal to the mean, normalized residual-limb length of the amputee group. External extension moments are defined as positive.</p