Saturation Diving Alters Folate Status and Biomarkers of DNA Damage and Repair

Exposure to oxygen-rich environments can lead to oxidative damage, increased body iron stores, and changes in status of some vitamins, including folate. Assessing the type of oxidative damage in these environments and determining its relationships with changes in folate status are important for defining nutrient requirements and designing countermeasures to mitigate these effects. Responses of humans to oxidative stressors were examined in participants undergoing a saturation dive in an environment with increased partial pressure of oxygen, a NASA Extreme Environment Mission Operations mission. Six participants completed a 13-d saturation dive in a habitat 19 m below the ocean surface near Key Largo, FL. Fasting blood samples were collected before, twice during, and twice after the dive and analyzed for biochemical markers of iron status, oxidative damage, and vitamin status. Body iron stores and ferritin increased during the dive (P<0.001), with a concomitant decrease in RBC folate (P<0.001) and superoxide dismutase activity (P<0.001). Folate status was correlated with serum ferritin (Pearson r = −0.34, P<0.05). Peripheral blood mononuclear cell poly(ADP-ribose) increased during the dive and the increase was significant by the end of the dive (P<0.001); γ-H2AX did not change during the mission. Together, the data provide evidence that when body iron stores were elevated in a hyperoxic environment, a DNA damage repair response occurred in peripheral blood mononuclear cells, but double-stranded DNA damage did not. In addition, folate status decreases quickly in this environment, and this study provides evidence that folate requirements may be greater when body iron stores and DNA damage repair responses are elevated

Oxidized and Aggregated Recombinant Human Interferon Beta is Immunogenic in Human Interferon Beta Transgenic Mice

PurposeTo study the effect of oxidation on the structure of recombinant human interferon beta-1a (rhIFNβ-1a) and its immunogenicity in wild-type and immune-tolerant transgenic mice.MethodsUntreated rhIFNβ-1a was degraded by metal-catalyzed oxidation, H2O2-mediated oxidation, and guanidine-mediated unfolding/refolding. Four rhIFNβ-1a preparations with different levels of oxidation and aggregation were injected intraperitoneally in mice 15× during 3 weeks. Both binding and neutralizing antibodies were measured.ResultsAll rhIFNβ-1a preparations contained substantial amounts of aggregates. Metal-catalyzed oxidized rhIFNβ-1a contained high levels of covalent aggregates as compared with untreated rhIFNβ-1a. H2O2-treated rhIFNβ-1a showed an increase in oligomer and unrecovered protein content by HP-SEC; RP-HPLC revealed protein oxidation. Guanidine-treated rhIFNβ-1a mostly consisted of dimers and oligomers and some non-covalent aggregates smaller in size than those in untreated rhIFNβ-1a. All degraded samples showed alterations in tertiary protein structure. Wild-type mice showed equally high antibody responses against all preparations. Transgenic mice were discriminative, showing elevated antibody responses against both metal-catalyzed oxidized and H2O2-treated rhIFNβ-1a as compared to untreated and guanidine-treated rhIFNβ-1a.ConclusionsOxidation-mediated aggregation increased the immunogenicity of rhIFNβ-1a in transgenic mice, whereas aggregated preparations devoid of measurable oxidation levels were hardly immunogenic

Using Minimum Path Cover to Boost Dynamic Programming on DAGs : Co-linear Chaining Extended

Peer reviewe

Lack of long-term acclimation in Antarctic encrusting species suggests vulnerability to warming

Marine encrusting communities play vital roles in benthic ecosystems and have major economic implications with regards to biofouling. However, their ability to persist under projected warming scenarios remains poorly understood and is difficult to study under realistic conditions. Here, using heated settlement panel technologies, we show that after 18 months Antarctic encrusting communities do not acclimate to either +1 °C or +2 °C above ambient temperatures. There is significant up-regulation of the cellular stress response in warmed animals, their upper lethal temperatures decline with increasing ambient temperature and population genetic analyses show little evidence of differential survival of genotypes with treatment. By contrast, biofilm bacterial communities show no significant differences in community structure with temperature. Thus, metazoan and bacterial responses differ dramatically, suggesting that ecosystem responses to future climate change are likely to be far more complex than previously anticipated

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Transition from n- to p-type conduction concomitant with enhancement of figure-of-merit in Pb doped bismuth telluride: Material to device development

The majority of industrial, automobile processes, electrical appliances emit waste heat in the low-temperature range (<573 K), hence efficient thermoelectric materials operating in this range are highly needed. Bismuth telluride (Bi2Te3) based alloys are conventional thermoelectric material for the low-temperature application. The pure Bi2Te3 sample synthesized in this work exhibits n-type conduction. We demonstrate that by small doping of Pb at Bi site a transition in electrical transport form n- to p-type is observed. The figure-of-merit (ZT) of n-type Bi2Te3 is similar to 0.47 and optimized Bi1.95Pb0.05Te3 exhibit p-type conduction with enhanced ZT of similar to 0.63 at 386 K. The conversion efficiency of Bi1.95Pb0.05Te3 based single thermoelement with hot pressed Ni/Ag electrical contacts was found to be similar to 4.9% for a temperature difference (Delta T) of 200 K. The efficiency was further enhanced to similar to 12% (at Delta T similar to 494 K) in the segmented thermoelement consisting of Bi1.95Pb0.05Te3 and (AgSbTe2)(0.15)(GeTe)(0.85) (i.e. TAGS-85). (C) 2018 Elsevier Ltd. All rights reserved

On the Physicochemical and Structural Modifications Associated with HIV-1 Subtype B Tropism Transition

HIV-1 enters immune cells via binding the viral envelope to a host cell CD4 receptor, and then a secondary co-receptor, usually CCR5 (R5) or CXCR4 (X4), and some HIV can utilize both co-receptors (R5X4). Although a small set of amino-acid properties such as charge and sequence length applied to HIV-1 envelope V3 loop sequence data can be used to predict co-receptor usage, we sought to expand the fundamental understanding of the physiochemical basis of tropism by analyzing many, perhaps less obvious, amino-acid properties over a diverse array of HIV sequences. We examined 74 amino-acid physicochemical scales over 1,559 V3 loop sequences with biologically tested tropisms downloaded from the Los Alamos HIV sequence database. Linear regressions were then calculated for each feature relative to three tropism transitions (R5→X4; R5→R5X4; R5X4→X4). Independent correlations were rank ordered to determine informative features. A structural analysis of the V3 loop was performed to better interpret these findings relative to HIV tropism states. Similar structural changes are required for R5 and R5X4 to transition to X4, thus suggesting that R5 and R5X4 types are more similar than either phenotype is to X4. Overall, the analysis suggests a continuum of viral tropism that is only partially related to charge; in fact, the analysis suggests that charge modification may be primarily attributed to decreased R5 usage, and further structural changes, particularly those associated with β-sheet structure, are likely required for full X4 usage