Abstract
Background
Human noroviruses (HuNoV) are the leading cause of gastroenteritis. No vaccine is currently available to prevent norovirus illness or infection. Safe, infectious challenge strains ...are needed to assess vaccine efficacy in the controlled human infection model (CHIM).
Methods
A stock of HuNoV strain Norwalk virus (NV GI.1) was prepared. Healthy, genetically susceptible adults were inoculated with NV Lot 001-09NV and monitored for infection, gastroenteritis symptoms, and immune responses.
Results
Lot 001-09NV induced gastroenteritis in 9 (56%) and infection in 11 (69%) of 16 genetically susceptible subjects. All infected subjects developed strong immune responses to GI.1 with a 30-fold (geometric mean titer) increase in blocking titers (BT50) and a 161-fold increase in GI.1-specific immunoglobulin (Ig)G titers when compared with baseline. GI.1-specific cellular responses in peripheral blood were observed 9 days postchallenge with an average of 3253 IgA and 1227 IgG antibody-secreting cells per million peripheral blood mononuclear cells.
Conclusions
GI.1 Lot 001-09NV appears to be similar in virulence to previous passages of NV strain 8fIIa. The safety profile, attack rate, and duration of illness make GI.1 Lot 001-09NV a useful challenge strain for future vaccine studies aimed at establishing immune correlates.
A new robust platform for the purification of a novel GI.1 human norovirus stock, Lot 001-09NV, produced an infectious inoculum that can be used to compare and standardize immune response levels and efficacy of future norovirus vaccine candidates.
Dissolved organic carbon (DOC) impacts water quality, the carbon cycle, and the ecology of aquatic systems. Understanding what controls DOC is therefore critical for improving large-scale models and ...best management practices for aquatic ecosystems. The two main processes of DOC transformation and removal, photochemical and microbial DOC degradation, work in tandem to modify and remineralize DOC within natural waters. Here, we examined both the photo- and microbial remineralization of DOC (photolability and biolability), and the indirect phototransformation of DOC into biolabile DOC (photoprimed biolability) for samples that capture the spatiotemporal and hydrological gradients of the Connecticut River watershed. The majority of DOC exported from this temperate watershed was photolabile and the concentration of photolabile DOC correlated with UV absorbance at 254 nm (
r
2
= 0.86). Phototransformation of DOC also increased biolability, and the total photolabile DOC (sum of photolabile and photoprimed biolabile DOC) showed a stronger correlation with UV absorbance at 254 nm (r
2
= 0.92). We estimate that as much as 49% (SD = 3.3%) and 10% (SD = 1.1%) of annual DOC export from the Connecticut River is directly photolabile and photoprimable, respectively. Thus, 2.82 Gg C year
−1
(SD = 0.67 Gg C year
−1
) or 1.13 Mg C km
−2
year
−1
(SD = 0.27 km
−2
year
−1
) of total photolabile DOC escapes photochemical degradation within the river network to be exported from the Connecticut River each year.
In Saccharomyces cerevisiae, Rad51p plays a central role in homologous recombination and the repair of double-strand breaks (DSBs). Double mutants of the two Zea mays L. (maize) rad51 homologs are ...viable and develop well under normal conditions, but are male sterile and have substantially reduced seed set. Light microscopic analyses of male meiosis in these plants reveal reduced homologous pairing, synapsis of nonhomologous chromosomes, reduced bivalents at diakinesis, numerous chromosome breaks at anaphase I, and that >33% of quartets carry cells that either lack an organized nucleolus or have two nucleoli. This indicates that RAD51 is required for efficient chromosome pairing and its absence results in nonhomologous pairing and synapsis. These phenotypes differ from those of an Arabidopsis rad51 mutant that exhibits completely disrupted chromosome pairing and synapsis during meiosis. Unexpectedly, surviving female gametes produced by maize rad51 double mutants are euploid and exhibit near-normal rates of meiotic crossovers. The finding that maize rad51 double mutant embryos are extremely susceptible to radiation-induced DSBs demonstrates a conserved role for RAD51 in the repair of mitotic DSBs in plants, vertebrates, and yeast.
To conduct a randomized prospective trial of immune globulin treatment for 105 Rh+ children with newly-diagnosed immune thrombocytopenic purpura and a platelet count < 20,000/μL, to determine whether ...anti-D immune globulin (anti-D) is as effective as intravenous immune globulin (IVIg).
Eligible patients received either a single intravenous dose of 50 μg/kg anti-D (anti-D50), 75 μg/kg anti-D, (anti-D75), or 0.8 g/kg IVIg, (IVIg). Patients were monitored for response to treatment and adverse events.
By 24 hours after treatment 50%, 72%, and 77% of patients in the anti-D50, anti-D75, and IVIg groups, respectively, had achieved a platelet count >20,000/μL (
P = .03). By day 7, hemoglobin concentrations decreased by 1.6 g/dL, 2 g/dL, and 0.3 g/dL in the anti-D50, anti-D75, and IVIg groups, respectively. Headache, fever, or chills occurred least often in the anti-D50 group.
A single 75μg/kg dose of Anti-D raised the platelet count in children with newly diagnosed immune thrombocytopenic purpura more rapidly than standard-dose anti-D and as effectively as IVIg, with an acceptable safety profile.
Nitrous oxide (N2O) evasion from streams and rivers is a significant, yet highly uncertain, flux in nitrogen cycle models. Most global estimates of lotic N2O emission assume that evasion rates are ...proportional to inorganic nitrogen inputs to a stream or river. However, many field studies do not detect relationships between lotic N2O evasion and dissolved nitrogen concentration, highlighting the need for better understanding of process‐based controls on this flux. This study reports 4‐yr time series of pN2O and N2O evasion from eight nested streams and rivers and detects an abrupt change in N2O dynamics associated with an intense rainstorm. This rainstorm, and the associated hydrologic flood event, pushed forested reaches across the watershed from consistent N2O sources to prolonged N2O sinks. We attribute this shift to disturbance of incomplete denitrification in the stream network and surrounding watershed, although alternate hypotheses are also discussed. There was continued availability of nitrate (NO3−) for in‐stream processing, eliminating the possibility that NO3−‐availability limited N2O production, and post‐storm N2O‐to‐nitrate ratios were lower than pre‐storm ratios suggesting that the large storm affected in‐situ nitrogen processing rates. The sustained period of post‐storm N2O undersaturation resulted in net negative evasion for five of the eight study sites in 2018, which mitigated emissions over the 4‐yr study. This nonlinear response in N2O dynamics illustrates the potential importance of storm events to control lotic N2O production and emissions.
Streams and rivers are significant sources of carbon dioxide (CO2) and methane (CH4) to the atmosphere. However, the magnitudes of these fluxes are uncertain, in part, because dissolved greenhouse ...gases (GHGs) can exhibit high spatiotemporal variability. Concentration‐discharge (C‐Q) relationships are commonly used to describe temporal variability stemming from hydrologic controls on solute production and transport. This study assesses how the partial pressures of two GHGs—pCO2 and pCH4—vary across hydrologic conditions over 4 yr in eight nested streams and rivers, at both annual and seasonal timescales. Overall, the range of pCO2 was constrained, ranging from undersaturated to nine times oversaturated, while pCH4 was highly variable, ranging from 3 to 500 times oversaturated. We show that pCO2 exhibited chemostatic behavior (i.e., no change with Q), in part, due to carbonate buffering and seasonally specific storm responses. In contrast, we show that pCH4 generally exhibited source limitation (i.e., a negative relationship with Q), which we attribute to temperature‐mediated production. However, pCH4 exhibited chemostasis in a wetland‐draining stream, likely due to hydrologic connection to the CH4‐rich wetland. These findings have implications for CO2 and CH4 fluxes, which are controlled by concentrations and gas transfer velocities. At high Q, enhanced gas transfer velocity acts on a relatively constant CO2 stock but on a diminishing CH4 stock. In other words, CO2 fluxes increase with Q, while CH4 fluxes are modulated by the divergent Q dynamics of gas transfer velocity and concentration.
Abstract
Nitrous oxide (N
2
O) evasion from streams and rivers is a significant, yet highly uncertain, flux in nitrogen cycle models. Most global estimates of lotic N
2
O emission assume that evasion ...rates are proportional to inorganic nitrogen inputs to a stream or river. However, many field studies do not detect relationships between lotic N
2
O evasion and dissolved nitrogen concentration, highlighting the need for better understanding of process‐based controls on this flux. This study reports 4‐yr time series of
p
N
2
O and N
2
O evasion from eight nested streams and rivers and detects an abrupt change in N
2
O dynamics associated with an intense rainstorm. This rainstorm, and the associated hydrologic flood event, pushed forested reaches across the watershed from consistent N
2
O sources to prolonged N
2
O sinks. We attribute this shift to disturbance of incomplete denitrification in the stream network and surrounding watershed, although alternate hypotheses are also discussed. There was continued availability of nitrate (
) for in‐stream processing, eliminating the possibility that
‐availability limited N
2
O production, and post‐storm N
2
O‐to‐nitrate ratios were lower than pre‐storm ratios suggesting that the large storm affected in‐situ nitrogen processing rates. The sustained period of post‐storm N
2
O undersaturation resulted in net negative evasion for five of the eight study sites in 2018, which mitigated emissions over the 4‐yr study. This nonlinear response in N
2
O dynamics illustrates the potential importance of storm events to control lotic N
2
O production and emissions.
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