Lack of Significant Elevation of Myeloid-Derived Suppressor Cells in Peripheral Blood of Chronically Hepatitis C Virus-Infected Individuals

Myeloid-derived suppressor cells (MDSC) are immature myeloid cells with immunosuppressive function. Compared to the level in healthy controls (HC), no elevation of MDSC in chronic hepatitis C (cHEP-C) patients was found, and there was no difference in MDSC based on genotype or viral load (P > 0.25). Moreover, MDSC of cHEP-C patients inhibited CD8 T cell function as efficiently as MDSC of HC did. Since we detected neither quantitative nor qualitative differences in MDSC of cHEP-C patients relative to those of HC, we postulate that MDSC in peripheral blood are most likely not significant regarding immune dysfunction in cHEP-C.     

Nutrients are assimilated efficiently by Lymantria dispar caterpillars from the mature leaves of trees in the Salicaceae

The efficient aquisition of nutrients from leaves by insect herbivores increases their nutrient assimilation rates and overall fitness. Caterpillars of the gypsy moth (Lymantria dispar L.) have high protein assimilation efficiencies (PAE) from the immature leaves of trees such as red oak (Quercus rubra) and sugar maple (Acer saccharum) (71–81%) but significantly lower PAE from their mature leaves (45–52%). By contrast to this pattern, both PAE and carbohydrate assimilation efficiencies (CAE) remain high for L. dispar larvae on the mature leaves of poplar (Populus alba × Populus tremula) grown in greenhouse conditions. The present study tests two alternative hypotheses: (i) outdoor environmental stresses cause decreased nutrient assimilation efficiencies from mature poplar leaves and (ii) nutrients in the mature leaves of trees in the poplar family (Salicaceae) remain readily available for L. dispar larvae. When poplar trees are grown in ambient outdoor conditions, PAE and CAE remain high (approximately 75% and 78%, respectively) in L. dispar larvae, in contrast to the first hypothesis. When larvae feed on the mature leaves of species in the Salicaceae [aspen (Populus tremuloides), cottonwood (Populus deltoides), willow (Salix nigra) and poplar], PAE and CAE also remain high (68–76% and 72–92%, respectively), consistent with the second hypothesis. Larval growth rates are strongly associated with protein assimilation rates, and more strongly associated with protein assimilation rates than with carbohydrate assimilation rates. It is concluded that tree species in the Salicaceae are relatively high‐quality host plants for L. dispar larvae, in part, because nutrients in their mature leaves remain readily available.     

Altitudinal distribution limits of aquatic macroinvertebrates: an experimental test in a tropical alpine stream

1. Temperature and oxygen are recognised as the main drivers of altitudinal limits of species distributions. However, the two factors are linked, and both decrease with altitude, why their effects are difficult to disentangle. 2. This was experimentally addressed using aquatic macroinvertebrates; larvae of Andesiops (Ephemeroptera), Claudioperla, (Plecoptera), Scirtes (Coleoptera) and Anomalocosmoecus (Trichoptera), and the amphipod Hyalella in an Ecuadorian glacier‐fed stream (4100–4500 m a.s.l.). The following were performed: (i) quantitative benthic sampling at three sites to determine altitudinal patterns in population densities, (ii) transplants of the five taxa upstream of their natural altitudinal limit to test the short‐term (14 days) effect on survival, and (iii) in situ experiments of locomotory activity as a proxy for animal response to relatively small differences in temperature (5 °C vs. 10 °C) and oxygen saturation (55% vs. 62%). 3. The transplant experiment reduced survival to a varying degree among taxa, but Claudioperla survived well at a site where it did not naturally occur. In the in situ experiment, Scirtes and Hyalella decreased their activity at lower oxygen saturation, whereas Andesiops and Anomalocosmoecus did so at a low temperature. The decrease in activity from a high to a low temperature and oxygen for the five taxa was significantly correlated with their mortality in the transplant experiment. 4. Together the present experiments indicate that even relatively small differences in temperature and oxygen may produce effects explaining ecological patterns, and depending on the taxon, either water temperature or oxygen saturation, without clear interacting effects, are important drivers of altitudinal limits.     

Analysis of conformational motions and related key residue interactions responsible for a specific function of proteins with elastic network model

Protein collective motions play a critical role in many biochemical processes. How to predict the functional motions and the related key residue interactions in proteins is important for our understanding in the mechanism of the biochemical processes. Normal mode analysis (NMA) of the elastic network model (ENM) is one of the effective approaches to investigate the structure-encoded motions in proteins. However, the motion modes revealed by the conventional NMA approach do not necessarily correspond to a specific function of protein. In the present work, a new analysis method was proposed to identify the motion modes responsible for a specific function of proteins and then predict the key residue interactions involved in the functional motions by using a perturbation approach. In our method, an internal coordinate that accounts for the specific function was introduced, and the Cartesian coordinate space was transformed into the internal/Cartesian space by using linear approximation, where the introduced internal coordinate serves as one of the axes of the coordinate space. NMA of ENM in this internal/Cartesian space was performed and the function-relevant motion modes were identified according to their contributions to the specific function of proteins. Then the key residue interactions important for the functional motions of the protein were predicted as the interactions whose perturbation largely influences the fluctuation along the internal coordinate. Using our proposed methods, the maltose transporter (MalFGK₂) from E. Coli was studied. The functional motions and the key residue interactions that are related to the channel-gating function of this protein were successfully identified.     

Distinctive roles of receptor‐interacting protein kinases 1 and 3 in caspase‐independent cell death of L929

Upon tumour necrosis factor alpha (TNFα) stimulation, cells respond actively by way of cell survival, apoptosis or programmed necrosis. The receptor‐interacting proteins 1 (RIP1) and 3 (RIP3) are responsible for TNFα‐mediated programmed necrosis. To delineate the differential contributions of RIP3 and RIP1 to programmed necrosis, L929 cells were stimulated with TNFα, carbobenzoxy‐valyl‐alanyl‐aspartyl‐[O‐methyl]‐fluoromethylketone (zVAD) or zVAD along with TNFα following RNA interference against RIP1 and RIP3, respectively. RIP1 silencing did not protect cells from TNFα‐mediated cell death, while RIP3 down‐regulation made them refractory to TNFα. The heat shock protein 90 inhibitor geldanamycin (GA) down‐regulated both RIP1 and RIP3 expression, which rendered cells resistant to zVAD/TNFα‐mediated cell death but not to TNFα‐mediated cell death alone. Therefore, the protective effect of GA on zVAD/TNFα‐stimulated necrosis might be attributed to RIP3, not RIP1, down‐regulation. Pretreatment of L929 cells with rapamycin mitigated zVAD‐mediated cell death, while the autophagy inhibitor chloroquine did not affect necrotic cell death. Meanwhile, necrotic cell death by zVAD and TNFα was caused by reactive oxygen species generation and effectively diminished by lipid‐soluble butylated hydroxyanisole. Taken together, the results indicate that RIP1 and RIP3 can independently mediate death signals being transduced by two different death stimuli, zVAD and TNFα. Copyright © 2013 John Wiley & Sons, Ltd.