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Surface-level ozone (O3) is a secondary air pollutant that has adverse effects on human health. In the troposphere, O3 is produced in complex cycles of photochemical reactions involving nitrogen oxides (NOx) and volatile organic compounds (VOCs). Determining if O3 levels will be decreased by lowering NOx emissions (“NOx-sensitive”), VOC emissions (“VOC-sensitive”), or both (“the transition zone”) can be done by using the formaldehyde (HCHO; a VOC species) to nitrogen dioxide (NO2; a component of NOx) concentration ratio (HCHO/NO2; “FNR”). Generally, lower FNR values indicate VOC sensitivity, while higher values indicate NOx sensitivity. Despite being a highly populated region with coastal O3 air quality issues, the Lake Michigan region in the United States, including the Chicago, Illinois, metropolitan area (CMA), remains relatively understudied, especially from the satellite perspective. In this work, we present the first study that utilizes TROPOspheric Monitoring Instrument (TROPOMI) satellite data over the Lake Michigan region from 2019–2021 to assess changes in O3 precursor levels and the inferred O3 chemistry sensitivity between (1) O3 season days and CMA O3 exceedance days and (2) weekdays and weekends. Higher NO2 vertical column densities (VCDs), HCHO VCDs, and FNR values are seen throughout the study domain on exceedance days, indicating generally more NOx-sensitive O3 chemistry. The largest change occurs in the areal extent of the transition zone, which decreases by 40 % during exceedance days. Major urban cores in the domain (e.g., Chicago, Illinois; Gary, Indiana; and Milwaukee, Wisconsin) remain VOC-sensitive on exceedance days as the higher NO2 VCDs in these areas counterbalance the regionally higher HCHO VCDs. Utilizing 10 m wind analysis data, we show that the lake breeze circulation is stronger on exceedance days. The strengthening of the lake breeze causes stronger convergence of the wind field along the southwestern Lake Michigan coastline, which can concentrate NO2 emissions originating in this area. This finding provides a possible explanation for the higher TROPOMI NO2 VCDs over the urban core of Chicago on exceedance days. Investigation of 2 m air temperature analysis data reveals that temperatures are higher on exceedance days, which explains the stronger lake breeze circulation and provides a possible cause for the higher TROPOMI HCHO VCDs over the entire region (due to increased temperature-dependent biogenic VOC emissions). Comparing weekdays and weekends, higher FNR values throughout much of the region indicate increasingly NOx-sensitive O3 chemistry on weekends. These changes are driven by lower NO2 VCDs in urban areas, particularly in Chicago, and higher HCHO VCDs in the southern part of the domain on weekends. Overall, our analyses suggest that VOC emissions controls in major urban areas and NOx emissions controls throughout the entire domain are necessary to decrease O3 levels in the Lake Michigan region.

Surface-level ozone (O3) is a secondary air pollutant that has adverse effects on human health. In the troposphere, O3 is produced in complex cycles of photochemical reactions involving nitrogen oxides (NOx) and volatile organic compounds (VOCs). Determining if O3 levels will be decreased by lowering NOx emissions (“NOx-sensitive”), VOC emissions (“VOC-sensitive”), or both (“the transition zone”) can be done by using the formaldehyde (HCHO; a VOC species) to nitrogen dioxide (NO2; a component of NOx) concentration ratio (HCHO/NO2; “FNR”). Generally, lower FNR values indicate VOC sensitivity, while higher values indicate NOx sensitivity. Despite being a highly populated region with coastal O3 air quality issues, the Lake Michigan region in the United States, including the Chicago, Illinois, metropolitan area (CMA), remains relatively understudied, especially from the satellite perspective. In this work, we present the first study that utilizes TROPOspheric Monitoring Instrument (TROPOMI) satellite data over the Lake Michigan region from 2019–2021 to assess changes in O3 precursor levels and the inferred O3 chemistry sensitivity between (1) O3 season days and CMA O3 exceedance days and (2) weekdays and weekends. Higher NO2 vertical column densities (VCDs), HCHO VCDs, and FNR values are seen throughout the study domain on exceedance days, indicating generally more NOx-sensitive O3 chemistry. The largest change occurs in the areal extent of the transition zone, which decreases by 40 % during exceedance days. Major urban cores in the domain (e.g., Chicago, Illinois; Gary, Indiana; and Milwaukee, Wisconsin) remain VOC-sensitive on exceedance days as the higher NO2 VCDs in these areas counterbalance the regionally higher HCHO VCDs. Utilizing 10 m wind analysis data, we show that the lake breeze circulation is stronger on exceedance days. The strengthening of the lake breeze causes stronger convergence of the wind field along the southwestern Lake Michigan coastline, which can concentrate NO2 emissions originating in this area. This finding provides a possible explanation for the higher TROPOMI NO2 VCDs over the urban core of Chicago on exceedance days. Investigation of 2 m air temperature analysis data reveals that temperatures are higher on exceedance days, which explains the stronger lake breeze circulation and provides a possible cause for the higher TROPOMI HCHO VCDs over the entire region (due to increased temperature-dependent biogenic VOC emissions). Comparing weekdays and weekends, higher FNR values throughout much of the region indicate increasingly NOx-sensitive O3 chemistry on weekends. These changes are driven by lower NO2 VCDs in urban areas, particularly in Chicago, and higher HCHO VCDs in the southern part of the domain on weekends. Overall, our analyses suggest that VOC emissions controls in major urban areas and NOx emissions controls throughout the entire domain are necessary to decrease O3 levels in the Lake Michigan region.

We evaluate two high-resolution Lake Michigan air quality simulations during the 2017 Lake Michigan Ozone Study campaign. These air quality simulations employ identical chemical configurations but use different input meteorology. The “EPA” configuration follows EPA recommended modeling practices, whereas the "YNT SSNG” employs different parameterization schemes and satellite-based inputs of sea surface temperatures, green vegetative fraction, and soil moisture and temperature. Overall, we find similar performance in model simulations of hourly and daily 8-hour maximum (MDA8) ozone, with the EPA and YNT_SSNG simulations showing biases of −13.31 and −13.54 ppbv, respectively during periods when the observed MDA8 was greater than 70 ppbv. However, for the two monitoring sites that observed high ozone events, the EPA simulation better matched observations at Sheboygan KA and the YNT_SSNG simulation better matched observations at Chiwaukee Prairie. We find differences between the two simulations are largest for column amounts of ozone precursors, particularly NO2. Across three high ozone events, the YNT_SSNG simulation has a lower column NO2 bias (0.17 × 1015 molecules/cm2) compared to the EPA simulation (0.35 × 1015 molecules/cm2). The YNT_SSNG simulation also has an advantage in better capturing the structure of the boundary layer and lake breeze during the June 2 high ozone event, although the timing of the lake breeze is about 3 hours too early. Our results are useful in informing an air quality modeling framework for the Lake Michigan area.

A record high evaporation rate of 98.7 kg m−2 h−1 with high energy conversion efficiency (81.1%) was achieved by applying electrical power to an artificial porous black body, enabling the successful creation of practical applications.

Multiple neurodegenerative disorders, including Parkinson’s disease (PD) and Alzheimer’s disease-associated dementia (ADAD), are linked with dopaminergic (DA) neuron death and a resulting reduction in dopamine levels in the brain. DA neuron degeneration and the risk of developing PD is connected to genetic mutations affiliated with lysosomal function and protein degradation. Accessible human cellular models for PD-relevant genetic mutations are needed to investigate mechanisms of DA cell death and define points of therapeutic intervention. Human induced pluripotent stem cell (iPSC)-derived midbrain DA neurons offer a developmentally and physiologically relevantin vitromodel for investigating PD pathogenic mechanisms across genetic backgrounds. In this study, we generated DA neurons using iPSCs from two clinically diagnosed PD patients, one harboring an inheritedGBAN370Smutation and the other a mutation inLRRK2G2019Sand compared pathophysiology against DA neurons from genetically engineeredSNCAA53TiPSCs and its isogenic apparently healthy normal (AHN) iPSCs. Our results present a novel phenotype forGBAN370SandLRRK2G2019Sderived DA neurons, showing that they produced and released significantly more dopamine compared to the AHN andSNCAA53Tmutant DA neurons. All mutant DA neurons developed deficient glucocerebrosidase (GCase) activity, increased mitochondrial stress, aberrant neuronal activity patterns, and increased α-synuclein accumulation. Together these data suggest potentially divergent origins of PD pathogenesis inGBAN370SandLRRK2G2019SDA neurons. In addition, compound screening confirmed that GCase modulators can rescue enzyme activity and impact neural activity across all DA mutant neurons, to varying degrees. These data demonstrate uniquein vitrophenotypes associated with PD and suggest a diversity of underlying mechanisms across different genetic backgrounds. Together, the cell lines used in this study present a valuable tool for new therapeutic discovery.

Recursive splicing is a noncanonical splicing mechanism in which an intron is removed in segments via multiple splicing reactions. Relatively few recursive splice sites have been identified with high confidence in human introns, and more comprehensive analyses are needed to better characterize where recursive splicing happens and whether or not it has a regulatory function. In this study, we use an unbiased approach utilizing intron lariats to search for recursive splice sites in constitutive introns and alternative exons in the human transcriptome. We find evidence for recursive splicing in a broader range of intron sizes than previously reported and detail a new location for recursive splicing at the distal ends of cassette exons. Additionally, we identify evidence for the conservation of these recursive splice sites among higher vertebrates and the use of these sites to influence alternative exon exclusion. Together, our data demonstrate the prevalence of recursive splicing and its potential influence on gene expression through alternatively spliced isoforms.

Climate change is expected to shift the home range of sugar maple (Acer saccharum Marsh.) northward, thereby encroaching onto the southern range of present-day balsam fir (Abies balsamea (L.) Mill.) forests. Such a shift from coniferous to deciduous forest stands will affect several edaphic properties and potentially modify soil organic carbon (SOC) storage and stability. For example, the more labile deciduous litter should decompose faster than coniferous litter, potentially resulting in lower SOC storage in forest floors. On the other hand, labile deciduous litter may result in a greater microbial turnover of SOC, leading to more stable SOC in mineral-associated organic matter (C-MAOM) in the subsoil. To test these hypotheses, we surveyed 30 mature forest stands in three regions along the sugar maple–balsam fir ecotone in southern Quebec, Canada. We dug three soil pits in each stand and measured SOC stocks in the organic forest floor as well as across five depth increments (0-5, 5-10, 10-20, 20-30 and 30-40 cm) in the mineral soil. We incubated mineral soil samples from each depth for 51 weeks and monitored CO2 emissions rates, from which we quantified the bioreactive SOC pool. We derived two indices of microbial turnover of SOC at different soil depths based on δ13C signatures. Finally, we used a wet sieving procedure to assess the proportion of C-MAOM at each soil depth. Results revealed that SOC stocks were 27% greater in balsam fir than in sugar maple forests. Most of this difference was attributable to the thicker forest floors under balsam fir, in accordance with slower litter decomposition rates. CO2 emission rates in the first 10 weeks of incubation were higher in soil samples collected under sugar maple; thereafter, CO2 emission rates were higher in soil samples collected under balsam fir. As a result, the bioreactive SOC pool over the course of 51 weeks did not differ significantly between stand types. We found significant region × stand type interactions on both indices of microbial turnover as well as on the proportion of C-MAOM in the mineral soil. More specifically, only in one region was microbial turnover higher under sugar maple than under balsam fir. Likewise, the effect of stand type on the proportion of C-MAOM was significant in only one region, and this effect was contrary to expectations (i.e. balsam fir > sugar maple). We ascribe this unexpected result to the presence of earthworms, which we only found in sugar maple stands in this region. Although we did not find generalizable effects of stand type on SOC turnover and stability, we did find significant generalizable patterns of decreasing SOC bioreactivity, increasing microbial turnover and increasing C-MAOM with increasing soil depth. Taken collectively, our results suggest that a northward shift of sugar maple will cause a net release of CO2 to the atmosphere and potentially create a positive feedback on global warming.

Moss-associated cyanobacteria nitrogen (N2-) fixation can support moss growth and constitutes a major source of new N in boreal forest ecosystems. Moss-colonizing cyanobacterial biomass and their N2-fixation are usually considered linearly correlated. However, recent evidence showed that cyanobacterial biomass and N2-fixation can be disconnected, hinting that they might be affected by the different environmental and ecological drivers. These drivers are often studied using manipulative experiments (e.g. fertilization, incubation) and remain to be validated with complementary work in observational studies. Cyanobacteria are considered the major actors of N fixation. However, the nature and diversity of active microbial communities associated with feather mosses are still unclear and the effects of the environment on these community are vague.Using random forest, spearman correlations and linear mixed-effects models, we studied the main drivers of cyanobacterial biomass and N2-fixation of two dominant feather moss species collected over three years on a 1000-km latitudinal transect in the eastern Canadian boreal forest. Using RNA-based amplicon sequencing of the 16S rRNA and nifH genes we explored the active bacterial communities along this transect and along the moss shoot.We report that temperature, precipitation, and phosphorus were the main drivers of moss cyanobacterial biomass and that temperature, molybdenum and vanadium were the main drivers of N2-fixation. Cyanobacteria accounted for 33% of global bacterial communities and 65% of diazotrophic communities, respectively. Several cyanobacterial and proteobacterial methanotrophic genera, including poorly known taxa found for the first time on boreal feather mosses, were actively contributing to N2-fixation. We showed that bacteria were heterogeneously distributed along the moss shoot, with phototrophs being dominant in the apical part and methanotrophs being dominant in the basal part. Finally data showed that climate (temperature, precipitation), environmental variables (moss species, month, tree density) and nutrients (nitrogen, phosphorus, molybdenum, vanadium, iron) strongly shape the global and diazotrophic bacterial communities and create ecological niches on the moss shoot.This work provides new insights into the feather moss microbiome and its ecological and biogeochemical functions. Our data provides evidence that the feather moss microbiome plays crucial roles in supporting moss growth, health, and decomposition, as well as in the boreal forest carbon and nitrogen cycles. Finally, this study highlights the strong effects of climate and nutrients in shaping feather moss microbiome and its activity (i.e., N2 fixation). This work will help better predict the impacts of global change on this symbiosis and on nitrogen input in boreal forest ecosystems.

Earthworms are newcomers to South-Eastern Canada, as they were unable to survive the last glaciation period that ended about 11,000 years ago. Since their introduction by Europeans over recent centuries, these exotic earthworm species have substantially affected pedological processes and soil functions. For example, a recent study in the province of Quebec found that earthworms invading native sugar maple (Acer saccharum Marsh.) forests could potentially increase soil nitrous oxide (N2O) emissions by increasing denitrification rates. However, the underlying microbial mechanisms driving the production of this greenhouse gas via denitrification remain unclear. This led us to conduct field and laboratory studies in order to explore whether earthworms preferentially promote bacterial and/or fungal denitrification pathways. We measured earthworm abundance and collected surface mineral soil samples from 38 sugar maple forests, half of which were earthworm-free. In each soil sample, we measured fungal, bacterial and total microbial biomass by substrate-induced respiration, we measured fungal, bacterial and total denitrification by acetylene inhibition, and we quantified the abundance bacterial (nirK, nirS and nosZ) and fungal (P450nor) denitrifying genes by qPCR. Earthworm abundance correlated positively with bacterial as well as fungal biomass, but did not affect the bacterial-to-fungal biomass ratio. Accordingly, bacterial-mediated and fungal-mediated denitrification rates both increased with the abundance of earthworms. However, earthworm abundance correlated positively with the specific bacterial denitrification rate (SBDR = (bacterial-mediated denitrification rate) ÷ (bacterial biomass)), but not with the specific fungal denitrification rate (SFDR = (fungal-mediated denitrification rate) ÷ (fungal biomass)). Moreover, qPCR analyses showed a positive correlation between earthworm abundance and the proportion of all bacterial denitrifying genes in the microbial population, but no such effect on fungal denitrifying genes. Taken collectively, our results suggest that earthworms may increase N2O emissions in sugar maple forest soils by preferentially promoting the bacterial-mediated denitrification pathway.

BackgroundMutations in the SF3B1 splicing factor are commonly seen in Myelodysplastic syndromes (MDS) and Acute Myeloid Leukemia (AML), yet the specific oncogenic pathways activated by missplicing have not been fully elucidated. Inflammatory immune pathways have been shown to play roles in pathogenesis of MDS, though the exact mechanisms of their activation in splicing mutant cases are not well understood.MethodsRNA-seq data from SF3B1 mutant samples was analyzed and functional roles of IRAK4 isoforms were determined. Efficacy of IRAK4 inhibition was evaluated in pre-clinical models of MDS/AMLResultsRNA-seq splicing analysis of innate immune mediators in SF3B1 mutant MDS samples revealed retention of full-length exon 6 of interleukin-1 receptor-associated kinase 4 (IRAK4), a critical downstream mediator that links the Myddosome to inflammatory NF-kB activation. Exon 6 retention leads to a longer isoform, encoding a protein (IRAK4-Long) that contains the entire death domain and kinase domain, leading to maximal activation of NF-kB. Cells with wild-type SF3B1 contain smaller IRAK4 isoforms that are targeted for proteosomal degradation. Expression of IRAK4-Long in SF3B1 mutant cells induces TRAF6 activation leading to K63-linked ubiquitination of CDK2, associated with a block in hematopoietic differentiation. Inhibition of IRAK4 with CA-4948, leads to reduction in NF-kB activation, inflammatory cytokine production, enhanced myeloid differentiation in vitro and reduced leukemic growth in xenograft models.ConclusionsSF3B1 mutation leads to expression of a therapeutically targetable, longer, oncogenic IRAK4 isoform in AML/MDS models.

Hierarchical structured ‘0D+ 2D+ 2D’ multidimensional nano carbon bowl (CB)-Molybdenum Disulfide (MoS2)-Graphene (CB@MoS2/Graphene) hybrid is a promising electrode material for high-performance energy storage. The semiconcave hollow carbon bowl (CB) with a high specific surface area can increase more active sites for uniform growth of MoS2 nanosheets. The unique bowl-shaped structure also helps to increase the contact area between adjacent particles, shorten the transmission distance of electrolyte ions and improve the rapid charge and discharge performance of the material. To further overcome the poor conductivity of pure MoS2 and efficiently display its energy storage performance, the hierarchical CB@MoS2/Graphene ‘0D+ 2D+ 2D’ multidimensional structured electrodes were synthesized by the hydrothermal method. As a ‘conductive bridge’, graphene was wrapped outside the surface of the CB@MoS2 to form a continuous conductive network channel in the GO-MoS2-CB hierarchical structure for better charge and ion transport. Moreover, the CB@MoS2 can also be used as a ‘spacer’ for graphene, alleviating the agglomeration of graphene sheets and providing part of the electric double-layer capacitance. When was used as the electrode material for supercapacitors, CB@MoS2/Graphene can obtain a better electrochemical property than CB@MoS2 and CB. The specific capacitance of CB@MoS2/Graphene can reach 588 F g−1 at a current density of 0.2 A g−1 and 398 F g−1 at high current density of 10 A g−1, respectively. In addition, the 2D graphene nanosheets can not only improve the electrical conductivity, but also can be used as a buffer to alleviate structural changes during the long-term charging and discharging process, improving the cycling performance. The capacitance retention of CB@MoS2/Graphene is enhanced to 83.9% after 5000 cycles.