NK cells and Lipoxin A4 promote resolution of eosinophilic inflammation after nasal allergen challenge

Density functional theory (DFT) calculations were adopted in this work to investigate the ability of the B12N12 fullerene like nano-cage for sensing juglone (Jug) and one of its derivative (Jug-OH) using DFT based methods in gas phase, pentyl ethanoate (PE) and water. Results showed that B12N12 is able to adsorbed Jug preferentially by binding to one of the O-atom of its carbonyl groups. Based on NBO analysis, a charge transfer from the oxygen atoms of Jug and Jug-OH to the anti-bonding orbital of B was revealed. QTAIM analysis showed that the B12N12-Jug and B12N12-Jug-OH complexes are stabilized by a partially covalent B-O bond in addition to attractive non covalent interactions. The ability of Jug, Jug-OH as well as their complexes A and A-OH to scavenge radicals has been investigated via the usual hydrogen atom transfer (HAT) mechanism in the three media of study previously stated. Theoretical results revealed that in PE and water, the complexes are better antioxidant than Jug and Jug-OH. These results provide fundamental knowledge for the development of new antioxidant delivery careers.

The study was conducted in Lake Baringo and determined quantitative relationships between water level changes, water quality, and fishery production for informed lake basin management. Long-term (2008 to 2020) data on water level, water quality, and fisheries yields from Lake Baringo were analyzed using a combination of statistical methods. Linear and waveform regression analyses described patterns of lake level fluctuations over time while, Pearson’s correlation determined the concordance of lake level changes with water quality parameters, landings, and condition of fish species. PCA results grouped the study period into different years based on annual water quality variable levels. LOWESS analysis showed the decline of annual lake level amplitude over time with peak values in 1964 (8.6 m) and 2008 (9.4 m). The waveform regression significantly modeled lake level fluctuations as indexed by annual deviations from the long-term average (DLTM) and showed a 20-year oscillation between peak water levels in the lake. There were significant positive correlations of Water Level Fluctuations (WLFs) with water quality variables and water quality index (WQI) in Lake Baringo. Linear regression analyses showed a significant concordance (p < 0.05) between the annual fishery yield and the rising WLFs (r = 0.66). Overall, the results demonstrate that WLFs of Lake Baringo are a driver of fish species biomass and physico-chemical properties of the lake. We recommend the integration of fisheries yields, water quality assessment, and WLFs modeling at different temporal scales in the management of Afrotropical lake ecosystems

BACKGROUND. Myxomatous mitral valve prolapse (MVP) and mitral-annular disjunction (Barlow disease) are at-risk for ventricular arrhythmias (VA). Fibrosis involving the papillary muscles and/or the infero-basal left ventricular (LV) wall was reported at autopsy in sudden cardiac death (SCD) patients with MVP. METHODS AND RESULTS: Twenty-three patients with VA were enrolled, including five with syncope and four with a history of SCD. Electrophysiological parameters were correlated with VA patterns, ECG inferior negative T wave (nTW), and late gadolinium enhancement (LGE) assessed by cardiac magnetic resonance. Premature ventricular complex (PVC) burden was 12061.9±12994.6 /24 hours with a papillary-muscle type (PM-PVC) in 18 patients (68%). Twelve-lead ECG showed nTW in 12 patients (43.5%). A large Uni<8.3mV area (62.4+/- 45.5 cm2) was detected in the basal infero-lateral LV region in 12 (73%) patients, and in the papillary muscles (2.2+/-2.9 cm2) in 5 (30%) of 15 patients undergoing EAM. A concomitant Bi<1.5 mV area (5.0±1.0 cm2) was identified in 2 patients. A history of SCD, and the presence of nTW, and LGE were associated with a greater Uni<8.3mV extension: (32.8+/-3.1 cm2 vs. 9.2+/-8.7 cm2), nTW (20.1+/-11.0vs.4.1+/-3.8cm2), and LGE (19.2 ± 11.7 cm2 vs. 1.0 ± 2.0 cm2, p=0.013), respectively. All patients with PM-PVC had a Uni<8.3mV area. CONCLUSIONS: Low unipolar low voltage areas can be identified with EAM in the basal infero-lateral LV region and in the papillary muscles as a potential electrophysiological substrate for VA and SCD in patients with MVP and Barlow disease phenotype

Background: β-blockers are first-line therapy in patients with long QT syndrome (LQTS). However, β-blockers had genotype dependent efficacy (LQT1>LQT2>LQT3). Sodium channel blockers have been recommended as add-on therapy for LQT3 patients. However, the effect of sodium channel blockers in all LQT patients remains unknown. Methods: We conducted a systematic electronic search of PubMed, Embase and the Cochrane Library. Fixed effects model was used to assess the effect of sodium channel blockers on QTc, cardiac events (CEs), and the proportion of QTc≥500 ms and QTc≤460 ms in LQTS patients. Results: Pooled analysis of 14 studies with 213 LQTS patients showed that sodium channel blockers significantly shortened QTc by nearly 50 ms (MD -49.43, 95%CI -57.80 to -41.05, P<0.001), reduced the incidence of CEs (OR 0.12, 95%CI 0.04 to 0.32, P<0.001) and the proportion of QTc≥500 ms (OR 0.15, 95%CI 0.09 to 0.26, P<0.001), and increased the proportion of QTc≤460 ms (OR 18.00, 95%CI 7.49 to 43.26, P<0.001). Sodium channel blockers significantly shortened QTc both in LQT3 and non-LQT3 patients, while the QTc shortening effect in LQT3 was superior to that in non-LQT3 (57.39 ms vs. 36.61 ms). Mexiletine, flecainide, and ranolazine all significantly shortened QTc, and the QTc shortening effect by mexiletine was the best (60.70 ms vs. 49.08 ms vs. 50.10 ms). Conclusions: sodium channel blockers can be useful both in LQT3 and non-LQT3 patients. Mexiletine, flecainide and ranolazine significantly shortened QTc in LQTS patients, and the QTc shortening effect by mexiletine was the best.

Role of activation of the coagulation system in the pathogenesis of urticariaTaro Yasuma,1 Corina N. D’Alessandro-Gabazza,1 Tetsu Kobayashi,2 John Morser,3 Esteban C Gabazza.1*1Department of Immunology,2Department of Pulmonary and Critical Care Medicine, Mie University Faculty and Graduate School of Medicine, and Mie University Hospital, Edobashi 2-174, Tsu, Mie 514-8507, Japan.3Division of Hematology, Stanford University School of Medicine, 291 Campus Drive, Stanford, CA 94305, United States*Correspondence: Esteban C Gabazza, MD, PhD, Department of Immunology, Mie University Graduate School of Medicine, Edobashi 2-174, Postal Code 514-8507, Tsu-city, Mie, Japan. Tel.: +81 59 231 5017; fax: +81 59 231 5225.E-mail:[email protected] count: 590

Both the Norwegian Spring Spawning herring (Clupea harengus) and the Northeast Arctic cod (Gadus morhua) are examples of how the overexploitation of marine fish populations was leading to a strong reduction even so stock collapse, with a strong decline in the associated fisheries, followed by a recovery. Cod and herring are both part of the Barents Sea ecosystem, which experienced major warming events in the early (1920-1940) and late 20th century. While the collapse or near collapse of these stocks seems to be linked to instability created by overfishing and climate, the difference of population dynamics before and after is not fully understood. In particular, it is unclear how the changes in population dynamics before and after the collapses are associated with biotic interactions. The combination of the availability of unique long-term time series for herring and cod makes it a well-suited study system to investigate the effects of collapse. We examine how species interactions may differently affect the herring and cod population dynamic before and after a collapse. Particularly we explore, using a GAM modelling approach, how herring could affect cod and reciprocally. We found that the effect on herring of cod biomass that was generally positive (i.e., covariation) became negative after the collapse (i.e., predation or competition). Likewise a change occurred for the cod, the juvenile herring biomass that had no effect before the collapse had a negative one after. Our results indicate that population collapses may lead to altered inter-specific interactions as well as altered response to abiotic environmental variations. While the stocks are at similar abundance levels before and after the collapses the system is potentially different in its functioning and may require different management action.

Faced with adverse conditions, such as winter in temperate regions or hot and dry conditions in tropical regions, many insect species enter a state of diapause, a period of dormancy associated with a reduction or arrest of physical activity, development, and reproduction. Changes in common physiological pathways underlie diapause phenotypes in different insect species. However, most transcriptomic studies of diapause have not simultaneously evaluated and compared expression patterns in different tissues. Honey bees (Apis mellifera) represent a unique model system to study the mechanisms underpinning diapause. In winter, honey bees exhibit a classic diapause phenotype, with reduced metabolic activity, increased physiological nutritional resources, and altered hormonal profiles. However, winter bees actively heat their colony by vibrating their wing muscles; thus, this tissue is not quiescent. Here, we evaluated the transcriptional profiles of flight muscle tissue and fat body tissue (involved in nutrient storage, metabolism and immune function) of winter bees. We also evaluated two behavioral phenotypes of summer bees: nurses, which exhibit high nutritional stores and low flight activity, and foragers, which exhibit low nutritional stores and high flight activity. We found winter bees and nurses have similar fat body transcriptional profiles compared to foragers, whereas winter bees and foragers have similar flight muscle transcriptional profiles compared to nurses. Additionally, differentially expressed genes were enriched in diapause-related GO terms. Thus, honey bees exhibit tissue-specific transcriptional profiles associated with diapause, laying the groundwork for future studies evaluating the mechanisms, evolution, and consequences of this tissue-specific regulation.

Undergraduate field experiences (UFEs) are a prominent element of science education across many disciplines; however, empirical data regarding the outcomes are often limited. UFEs are unique in that they take place in a field setting, are often interdisciplinary, and include diverse students. UFEs range from courses, to field trips, to residential research experiences, and thereby have the potential to yield a plethora of outcomes for undergraduate participants. The UFE community has expressed a strong interest in better understanding how to assess the outcomes of UFEs. In response, we developed a strategy by which practitioners can assess their UFE using an evidence-based, systematic and iterative approach. This essay guides practitioners through the steps of: identifying intended UFE outcomes, considering contextual factors, determining an explicit assessment approach, and using the information to inform next steps. We provide a table of common learning outcomes and potential assessment tools, vignettes to illustrate using the strategy, and suggestions for practical application of the strategy. We aim to support comprehensive and aligned assessment of UFEs, leading to more inclusive and reflective design, and ultimately improved student outcomes. We urge practitioners to move towards evidence-based advocacy for continued support of UFEs.

Objective: To address the effectiveness and safety of early airway utilization of budesonide and surfactant for BPD prevention in premature infants with RDS. Methods: PubMed, Web of Science, EMBASE, Cochrane Library, Wanfang, CQ VIP and China National Knowledge Infrastructure databases were searched from the inception to May 2021. Stata 16.0 software was used for statistical analysis. Results: This meta-analysis suggested that early combined utilization of budesonide and surfactant by airway tended to have a superiority on BPD incidence (RR=0.63;95%CI:0.54～0.73, P<0.001), mortality (RR=0.63;95%CI:0.43～0.94, P=0.022) and the composite outcome of BPD or mortality (RR=0.59;95%CI:0.49～0.70, P<0.001), the reuse incidence of surfactant (RR=0.54; 95%CI:0.45～0.65, P<0.001), the duration of assisted ventilation (SMD=-1.14;95%CI: -1.58 ～ -0.70, P<0.001), invasive ventilation (SMD=-1.33;95%CI: -1.76～-0.90, P<0.001), and hospital stays (SMD=-1.20;95%CI: -1.88～-0.51, P=0.001) in preterm infants with RDS. And these benefits were not associated with increased adverse outcomes. Furthermore, a decreased incidence of PDA (RR=0.80; 95%CI:0.64～0.99, P=0.041) was found in test group. Subgroup analysis based on budesonide delivery methods (inhalation or intratracheal instillation) indicated that the decrease of mortality (RR=0.62;95%CI:0.41～0.95, P=0.026), duration of assisted ventilation (SMD=-0.95;95%CI: -1.30～-0.61, P<0.001) and hospital stays (SMD=-1.38;95%CI: -2.33～-0.43, P=0.004) were mainly in budesonide intratracheal instillation subgroup. Conclusions: This meta-analysis suggested that early combined utilization of budesonide and surfactant by airway might be an effective and safe clinical practice for BPD prevention in premature infants with RDS, especially when budesonide was delivered by intratracheal instillation.

Historically, bird song complexity was thought to evolve primarily through sexual selection on males, yet in many species both sexes sing. Previous research suggests competition for mates and resources during short, synchronous breeding seasons leads to more elaborate male songs at high latitudes. In contrast, we expect male-female song dimorphism and elaboration to be more similar at lower latitudes because longer breeding seasons and year-round territoriality yield similar social selection pressures in both sexes. However, studies seldom take both selective pressures and sexes into account. We examined song elaboration and sexual dimorphism in 15 populations of nine fairy-wren species (Maluridae), a Southern Hemisphere clade with female song. We compared song elaboration and sexual song dimorphism to latitude and life history variables tied to sexual and social selection pressures and sex roles. Our results suggest that song elaboration evolved in part due to sexual competition in males: male song variability was more positively correlated with temperate breeding and greater breeding synchrony than female song. We also found strong evidence that sex-role similarity contributed to male-female song similarity: male and female songs were shorter and more similar when parental care was more equal and when male survival was high. Contrary to Northern Hemisphere latitudinal patterns, songs were less dimorphic at higher, temperate latitudes. These results suggest that selection on song can be sex-specific, with male song elaboration favored in contexts coincident with sexual selection. However, selection pressures associated with sex-role similarity also appear to constrain sex specific song evolution and song dimorphism.

C-radical borylation is an significant approach for the construction of carbon−boron bond. Photochemical borylation of aryl halides successfully applied this strategy. However, precise mechanisms, such as the generation of aryl radicals and the role of base additive(TMDAM) and water, remain controversy in these reactions. In this study, photochemical borylation of aryl halides has been researched by density functional theory (DFT) calculations. Indeed, the homolytic cleavage of the C−X bond under irradiation with UV-light is a key step for generation of aryl radicals. Nevertheless, the generation of aryl radicals may also undergo the process of single electron transfer and the heterolytic carbon-halogen bond cleavage sequence, and the latter is favorable during the reaction.

While the impact of biodiversity, notably functional diversity, on ecosystem productivity has been extensively studied, little is known about the effect of individual species. Here, we identified species of high importance for productivity (key species) in over 28,000 diverse grassland communities in the European Alps, and compared their effects with those of community-level measures of functional composition (weighted means, variances, skewness, and kurtosis). After accounting for the environment, the five most important key species jointly explained more deviance than all statistics of functional composition. Key species were generally tall with high specific leaf areas. By dividing the observations according to distinct habitats, the explanatory power of all non-environmental predictors increased considerably, and the relationships between functional composition and productivity varied systematically, presumably because of changing interactions and trade-offs between traits. Our results advocate for a better consideration of species’ individual effects on ecosystem functioning in complement to community-level measures.

We have created a panel of twenty-nine NF1 variant cDNAs representing benign missense (MS) variants, pathogenic MS variants, many with clinically relevant phenotypes, in-frame deletions, splice variants, and nonsense (NS) variants. We have determined the functional consequences of the variants, assessing their ability to produce mature neurofibromin and restore Ras signaling activity in NF1 null (-/-) cells. cDNAs demonstrate variant-specific differences in neurofibromin protein levels, suggesting that some variants lead to protein instability or enhanced degradation. When expressed at high levels, some variant proteins are still able to repress Ras activity, indicating that the NF1 phenotype may be due to protein instability. In contrast, other variant proteins are incapable of repressing Ras activity, indicating that some do not functionally engage Ras and stimulate GTP-ase activity. We observed that stability and Ras activity can be mutually exclusive. These assays allow us to categorize variants by functional effects, may help to classify variants of unknown significance, and may have future implications for more directed therapeutics.

The UCSC Genome Browser has been an important tool for genomics and clinical genetics since the sequence of the human genome was first released in 2000. As it has grown in scope to display more types of data it has also grown more complicated. The data, which are dispersed at many locations worldwide, are collected into one view on the Browser, where the graphical interface presents the data in one location. This supports the expertise of the researcher to interpret variants in the genome. Because the analysis of Single Nucleotide Variants (SNVs) and Copy Number Variants (CNVs) require interpretation of data at very different genomic scales, different data resources are required. We present here several Recommended Track Sets designed to facilitate the interpretation of variants in the clinic, offering quick access to datasets relevant to the appropriate scale.

Background and Objective: Ectopic beats originating from the pulmonary vein (PV) trigger atrial fibrillation (AF). The purpose of this study was to clarify the electrophysiological determinant of AF initiation from the PVs. Methods: Pacing studies were performed with a single extra stimulus mimicking an ectopic beat in the left superior pulmonary veins (LSPVs) in 62 patients undergoing AF ablation. Inducibility of AF, effective refractory period (ERP) and conduction properties within the PVs were analyzed. Results: A single extra stimulus in LSPV induced AF in 20 patients (32% of all patients) at the mean coupling interval (CI) of 172 ms. A CI-dependent anisotropic conduction at the AF onset was visualized in a 3D-mapping. Onset of AF was site-specific with reproducibility in each individual. Mean ERP in LSPV in the AF inducible group was shorter than that in the AF non-inducible group (182 ± 55 ms vs 254 ± 51 ms, P<0.0001). LSPV ERP dispersion was greater in the AF inducible group than in the AF non-inducible group (45 ± 28 ms vs 27 ± 19 ms, P<0.01). Circumferential intra-PV conduction time (IPVCT) exhibited decremental properties in response to shortening of CI, and the prolongation of IPVCT in the AF inducible site was greater than that in the AF non-inducible site (P<0.05) in each individual. Conclusions: Location and coupling interval of an ectopic excitation ultimately determine the initiation of AF from the PVs. ERP dispersion and circumferential conduction delay may lead to anisotropic conduction and reentry within the PVs that initiate AF.

Aim: Metamizole (dipyrone) is a prodrug not detectable in serum or urine after oral ingestion. The primary metabolite is 4-methylaminoantipyrine (4-MAA), which can be N-demethylated to 4-aminoantipyrine (4-AA) or oxidized to 4-formylaminoantipyrine (4-FAA) by cytochrome P450 (CYP)-dependent reactions. Our aim was to identify the CYPs involved. Methods: We investigated the metabolism of 4-MAA in vitro using CYP expressing supersomes and the pharmacokinetics of metamizole in the presence of CYP inhibitors in healthy volunteers. Results: The experiments in supersomes revealed CYP1A2 as the major CYP for 4-MAA N-demethylation and 4-FAA formation. CYP2C19 and CYP2D6 contributed to N-demethylation but not to FAA formation. In the subsequent clinical study, we investigated the influence of ciprofloxacin (strong CYP1A2 inhibitor), fluconazole (strong CYP2C19 inhibitor) and the combination ciprofloxacin/fluconazole on the pharmacokinetics of a single dose of metamizole in n=12 healthy volunteers in a randomized, placebo-controlled, double-blind study. Both ciprofloxacin and fluconazole inhibited the metabolism of 4-MAA, confirming the in vitro results. Ciprofloxacin, fluconazole and ciprofloxacin/fluconazole increased the AUC0-12h of 4-MAA by 51%, 17% and 92%, respectively. Ciprofloxacin, fluconazole and ciprofloxacin/fluconazole decreased the AUC0-12h of 4-AA by 27%, 12% and 24%, respectively, and of 4-FAA by 33%, 9% and 51%, respectively. Ciprofloxacin, fluconazole and ciprofloxacin/fluconazole increased the half-life of 4-MAA from 3.22 h (placebo) to 3.91, 3.69 and 6.07 h, respectively. Conclusion: CYP1A2 is the major CYP for the conversion of 4-MAA to 4-AA and 4-FAA. CYP1A2 inhibition increases the 4-MAA exposure by a factor of approximately 1.5, which could be relevant for dose-dependent adverse reactions.

Objective The Model for End- Stage Liver Disease (MELD) score is a composite number of physiologic parameters and likely has non-linear effects on operative outcomes. . We use machine learning to evaluate the relationship between MELD score and outcomes of cardiac surgery. Methods All STS indexed elective cardiac surgical procedures at our institution between 2011 and 2018 were included. MELD score was retrospectively calculated. Logistic regression models and an imbalanced random forest classifier was created on operative mortality using 30 preoperative characteristics. Cox regression models and random forest survival models were created for long-term survival. Variable importance analysis (VIMP) was conducted to rank variables by predictive power. Linear and machine learned models were compared with their receiver operating characteristic (ROC) and Brier score respectively. Results The patient population included 3,872 individuals. Operative mortality was 1.7% and 5-year survival was 82.1%. MELD score was the 4th largest positive predictor on VIMP analysis for both operative long-term survival and the strongest negative predictor for operative mortality. The logistic model ROC area was 0.762, compared to the random forest classifier ROC of 0.674. The Brier score of the random forest survival model was larger (worse) than the cox regression starting at 2 years and continuing throughout the study period. Conclusions MELD score and other continuous variables had high degrees of non-linearity to mortality. This is demonstrated by the fact that MELD score was not significant in the cox multivariable regression but was strongly important in the random forest survival model.