Description: Intense atmosphere-ocean-ice interactions in the Ross Sea produce the most saline dense shelf waters around the Antarctic, supplying the lower limb of the global overturning circulation. Over the last 50 years, freshening in the Ross Sea shelf water contributed to a decrease in Antarctic Bottom Water (AABW) formation. The recent rebound of shelf water salinity in the Ross Sea since 2012 has been observed and suggested to be driven by wind anomalies. However, lack of observation on the continental shelf prevents a quantitative assessment of shelf water salinity response to wind and other atmospheric forcing. Here, we design perturbation experiments to investigate the causes of the observed salinity rebound using a global ocean-sea ice model. Our results show the recent salinity rebound in the whole water column (0-900 m) of the western Ross Sea was supplied by brine rejection from the surface through convection, which is induced by increased sea ice formation. We further find this increased sea ice formation was triggered by the combined effect of anomalous wind stress and surface heat flux, which have nearly equal impacts on salinity but through different mechanisms. Weakened easterlies reduced sea ice import into the western Ross Sea and decreased the local sea ice thickness and concentration in winter, which promotes sea ice formation. A negative heat flux anomaly decreased the surface temperature, leading to increased sea ice production in winter. The two mechanisms identified here will help to understand the implication of climate change on observed and projected changes in AABW.

Description: A rapid warming and freshening of the Southern Ocean have been observed over the past several decades and are attributed to anthropogenic climate change. We conducted ocean model perturbation experiments to separate roles of individual surface forcing in the Southern Ocean temperature and salinity changes. Model-based findings are compared with results from a theoretical framework including three idealized processes defined on the θ-S diagram. Under the future scenario of CO2 doubling, the heat flux forcing dominates the large-scale warming, deepening of isopycnals, and spiciness changes along isopycnals, which can be captured by an idealized pure warming process to represent the subduction of surface heat uptake. The poleward-intensifying westerly winds account for 24% of the enhanced warming between 35°and 50°S and would have comparable contribution as the heat flux forcing after removing the global ocean warming effect. In contrast, the widespread freshening in the Southern Ocean driven by increased surface freshwater input is largely compensated by the wind-driven saltening. The response to freshwater forcing could not be approximated as a similar pure freshening process as the induced cooling and freshening have comparable effects on density. The wind-driven changes are primarily through the local heave of isopycnals, thus resembling an idealized pure heave process, but contain considerable spiciness signals especially in the midlatitude Southern Ocean, resulting from anomalous northward transport and subduction of heat and salt that are largely density-compensating. These distinct signatures of individual surface forcing help us to better understand observed and projected changes in the Southern Ocean.

Description: Hand-foot-and-mouth disease (HFMD) remains a major health concern in the Asia-Pacific regions, and its major causative agents include human enterovirus 71 (EV71) and coxsackievirus A16. A desirable vaccine against HFMD would be multivalent and able to elicit protective responses against multiple HFMD causative agents. Previously, we have demonstrated that a thermostable recombinant EV71 vaccine candidate can be produced by the insertion of a foreign peptide into the BC loop of VP1 without affecting viral replication. Here we present crystal structures of two different naturally occurring empty particles, one from a clinical C4 strain EV71 and the other from its recombinant virus containing an insertion in the VP1 BC loop. Crystal structure analysis demonstrated that the inserted foreign peptide is well exposed on the particle surface without significant structural changes in the capsid. Importantly, such insertions do not seem to affect the virus uncoating process as illustrated by the conformational similarity between an uncoating intermediate of another recombinant virus and that of EV71. Especially, at least 18 residues from the N terminus of VP1 are transiently externalized. Altogether, our study provides insights into vaccine development against HFMD.

Description: Intensive rice breeding over the past 50 y has dramatically increased productivity especially in the indica subspecies, but our knowledge of the genomic changes associated with such improvement has been limited. In this study, we analyzed low-coverage sequencing data of 1,479 rice accessions from 73 countries, including landraces and modern...

Description: The development of vaccines against infectious diseases represents one of the most important contributions to medical science. However, vaccine-preventable diseases still cause millions of deaths each year due to the thermal instability and poor efficacy of vaccines. Using the human enterovirus type 71 vaccine strain as a model, we suggest...

Description: Accumulation and breakdown of large algal blooms often causes serious hypoxia in lakes, representing a major potential threat to zooplankton grazers such as Daphnia . Generally, populations comprise different age groups, whose molecular responses to environmental stressors are different. The aim of our study was to investigate the age-dependent effects of oxygen depletion on D. magna survival and selected gene expressions of energy-relevance and stress-defense. Four age groups of D. magna (1, 4, 7 and 14 days) were exposed to 0.0625, 0.125, 0.25 mM dissolved oxygen (DO) for 48 h. Results showed that survival rates of 14-day-old individuals in 0.0625 mM DO and 0.125 mM DO were much lower than those in 0.25 mM DO, while no significant difference was found in remaining age groups. Low DO up-regulated hemoglobin expression compared with the controls in all age groups; the similar pattern in α-esterase was observed when 1-day-old individuals were exposed to 0.0625 mM, 4- and 7-day-old individuals at 0.125 mM, respectively. HSP70 and CAT expression were significantly upregulated in 1- and 7-day-old individuals exposed to 0.125 mM. The findings indicate that age structure should be taken into account when interpreting dynamics of Daphnia populations affected by oxygen depletion. Age may modify energy reallocation and alter susceptibility of the organisms.

Description: Human enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the two major causative agents for hand-foot-and-mouth disease (HFMD). Previously, we demonstrated that a virus-like particle (VLP) for EV71 produced from Saccharomyces cerevisiae is a potential vaccine candidate against EV71 infection, and an EV71/CVA16 chimeric VLP can elicit protective immune responses against both virus infections. Here, we presented the crystal structures of both VLPs, showing that both the linear and conformational neutralization epitopes identified in EV71 are mostly preserved on both VLPs. The replacement of only 4 residues in the VP1 GH loop converted strongly negatively charged surface patches formed by portions of the SP70 epitope in EV71 VLP into a relatively neutral surface in the chimeric VLP, which likely accounted for the additional neutralization capability of the chimeric VLP against CVA16 infection. Such local variations in the amino acid sequences and the surface charge potential are also present in different types of polioviruses. In comparison to EV71 VLP, the chimeric VLP exhibits structural changes at the local site of amino acid replacement and the surface loops of all capsid proteins. This is consistent with the observation that the VP1 GH loop located near the pseudo-3-fold junction is involved in extensive interactions with other capsid regions. Furthermore, portions of VP0 and VP1 in EV71 VLP are at least transiently exposed, revealing the structural flexibility of the VLP. Together, our structural analysis provided insights into the structural basis of enterovirus neutralization and novel vaccine design against HFMD and other enterovirus-associated diseases. IMPORTANCE Our previous studies demonstrated that the enterovirus 71 (EV71) virus-like particle (VLP) produced from yeast is a vaccine candidate against EV71 infection and that a chimeric EV71/coxsackievirus A16 (CVA16) VLP with the replacement of 4 amino acids in the VP1 GH loop can confer protection against both EV71 and CVA16 infections. This study reported the crystal structures of both the EV71 VLP and the chimeric EV71/CVA16 VLP and revealed that the major neutralization epitopes of EV71 are mostly preserved in both VLPs. In addition, the mutated VP1 GH loop in the chimeric VLP is well exposed on the particle surface and exhibits a surface charge potential different from that contributed by the original VP1 GH loop in EV71 VLP. Together, this study provided insights into the structural basis of enterovirus neutralization and evidence that the yeast-produced VLPs can be developed into novel vaccines against hand-foot-and-mouth disease (HFMD) and other enterovirus-associated diseases.

Description: Human enterovirus 71 (EV71) is the major causative agent of severe hand-foot-and-mouth diseases (HFMD) in young children, and structural characterization of EV71 during its life cycle can aid in the development of therapeutics against HFMD. Here, we present the atomic structures of the full virion and an uncoating intermediate of a clinical EV71 C4 strain to illustrate the structural changes in the full virion that lead to the formation of the uncoating intermediate prepared for RNA release. Although the VP1 N-terminal regions observed to penetrate through the junction channel at the quasi-3-fold axis in the uncoating intermediate of coxsackievirus A16 were not observed in the EV71 uncoating intermediate, drastic conformational changes occur in this region, as has been observed in all capsid proteins. Additionally, the RNA genome interacts with the N-terminal extensions of VP1 and residues 32 to 36 of VP3, both of which are situated at the bottom of the junction. These observations highlight the importance of the junction for genome release. Furthermore, EV71 uncoating is associated with apparent rearrangements and expansion around the 2- and 5-fold axes without obvious changes around the 3-fold axes. Therefore, these structures enabled the identification of hot spots for capsid rearrangements, which led to the hypothesis that the protomer interface near the junction and the 2-fold axis permits the opening of large channels for the exit of polypeptides and viral RNA, which is an uncoating mechanism that is likely conserved in enteroviruses. IMPORTANCE Human enterovirus 71 (EV71) is the major causative agent of severe hand-foot-and-mouth diseases (HFMD) in young children. EV71 contains an RNA genome protected by an icosahedral capsid shell. Uncoating is essential in EV71 life cycle, which is characterized by conformational changes in the capsid to facilitate RNA release into host cell. Here we present the atomic structures of the full virion and an uncoating intermediate of a clinical C4 strain of EV71. Structural analysis revealed drastic conformational changes associated with uncoating in all the capsid proteins near the junction at the quasi-3-fold axis and protein-RNA interactions at the bottom of the junction in the uncoating intermediate. Significant capsid rearrangements also occur at the icosahedral 2- and 5-fold axes but not at the 3-fold axis. Taking the results together, we hypothesize that the junction and nearby areas are hot spots for capsid breaches for the exit of polypeptides and viral RNA during uncoating.

Description: Predictors of general discomfort, limitations in activities of daily living and intention of a second donation in unrelated hematopoietic stem cell donation Bone Marrow Transplantation 52, 258 (February 2017). doi:10.1038/bmt.2016.260 Authors: M H Lee, J H Jang, H J Min, H I Jang, J H Nah, C J Lyu, K-S Han, J H Won, Y-H Lee, S Y Chong, Y C Mun, W S Lee, S J Kim & I Kim