Microorganisms drive much of the Earth’s nitrogen (N) cycle, but we still lack a global overview of the abundance and composition of the microorganisms carrying out soil N processes. To address this gap, we characterized the biogeography of microbial N traits, defined as eight N-cycling pathways, using publically available soil metagenomes. The relative frequency of N pathways varied consistently across soils, such that the frequencies of the individual N pathways were positively correlated across the soil samples. Habitat type, soil carbon, and soil N largely explained the total N pathway frequency in a sample. In contrast, we could not identify major drivers of the taxonomic composition of the N functional groups. Further, the dominant genera encoding a pathway were generally similar among habitat types. The soil samples also revealed an unexpectedly high frequency of bacteria carrying the pathways required for dissimilatory nitrate reduction to ammonium, a little-studied N process in soil. Finally, phylogenetic analysis showed that some microbial groups seem to be N-cycling specialists or generalists. For instance, taxa within the Deltaproteobacteria encoded all eight N pathways, whereas those within the Cyanobacteria primarily encoded three pathways. Overall, this trait-based approach provides a baseline for investigating the relationship between microbial diversity and N cycling across global soils.

Global biogeography of microbial nitrogen-cycling traits in soil

Abstract The nitrogen cycle plays a major role in aquatic nitrogen transformations, including in the terrestrial subsurface. However, the variety of transformations remains understudied. To determine how nitrogen cycling microorganisms respond to different aquifer chemistries, we sampled groundwater with varying nutrient and oxygen contents. Genes and transcripts involved in major nitrogen-cycling pathways were quantified from 55 and 26 sites, respectively, and metagenomes and metatranscriptomes were analyzed from a subset of oxic and dysoxic sites (0.3-1.1 mg/L bulk dissolved oxygen). Nitrogen-cycling mechanisms (e.g. ammonia oxidation, denitrification, dissimilatory nitrate reduction to ammonium) were prevalent and highly redundant, regardless of site-specific physicochemistry or nitrate availability, and present in 40% of reconstructed genomes, suggesting that nitrogen cycling is a core function of aquifer communities. Transcriptional activity for nitrification, denitrification, nitrite-dependent anaerobic methane oxidation and anaerobic ammonia oxidation (anammox) occurred simultaneously in oxic and dysoxic groundwater, indicating the availability of oxic-anoxic interfaces. Concurrent activity by these microorganisms indicates potential synergisms through metabolite exchange across these interfaces (e.g. nitrite and oxygen). Fragmented denitrification pathway encoding and transcription was widespread among groundwater bacteria, although a considerable proportion of associated transcriptional activity was driven by complete denitrifiers, especially under dysoxic conditions. Despite large differences in transcription, the capacity for the final steps of denitrification was largely invariant to aquifer conditions, and most genes and transcripts encoding N 2 O reductases were the atypical Sec-dependant type, suggesting energy-efficiency prioritization. Results provide insights into the capacity for cooperative relationships in groundwater communities, and the richness and complexity of metabolic mechanisms leading to the loss of fixed nitrogen. 

/pdf/nitrogen-cycling-and-microbial-cooperation-in-the-3w5fae3r.pdf

Nitrogen cycling and microbial cooperation in the terrestrial subsurface

Selenium (Se) reduces Sclerotinia stem rot disease incidence of oilseed rape by increasing plant Se concentration and shifting soil microbial community and functional profiles.

Soil microbial communities are intricately linked to ecosystem functioning such as nutrient cycling; therefore, a predictive understanding of how these communities respond to environmental changes is of great interest. Here, we test whether phylogenetic information can predict the response of bacterial taxa to nitrogen (N) addition. We analyze the composition of soil bacterial communities in 13 field experiments across 5 continents and find that the N response of bacteria is phylogenetically conserved at each location. Remarkably, the phylogenetic pattern of N responses is similar when merging data across locations. Thus, we can identify bacterial clades - the size of which are highly variable across the bacterial tree - that respond consistently to N addition across locations. Our findings suggest that a phylogenetic approach may be useful in predicting shifts in microbial community composition in the face of other environmental changes.

/pdf/phylogenetic-conservation-of-bacterial-responses-to-soil-2wiuv5ybq9.pdf

Phylogenetic conservation of bacterial responses to soil nitrogen addition across continents.

Biogeographical distributions of nitrogen-cycling functional genes in a subtropical estuary

Despite the explosion of metagenomic sequencing data, using -omics data to predict environmental biogeochemistry remains a challenge. One or a few genes (referred to as marker genes) in a metabolic pathway of interest in meta-omic data are typically used to represent the prevalence of a biogeochemical reaction. This approach often fails to demonstrate a consistent relationship between gene abundance and an ecosystem process rate. One reason this may occur is if a marker gene is not a good representative of a complete pathway. Here, we map the presence of 11 nitrogen (N)-cycling pathways in over 6000 complete bacterial and archaeal genomes using the Integrated Microbial Genomes database. Incomplete N-cycling pathways occurred in 39% of surveyed archaeal and bacterial species revealing a weakness in current marker-gene analyses. Furthermore, we found that most organisms have limited ability to utilize inorganic N in multiple oxidation states. This suggests that inter-organism exchange of inorganic N compounds is common, highlighting the importance of both community composition and spatial structure in determining the extent of recycling versus loss in an ecosystem.

Comparative Genomics of Nitrogen Cycling Pathways in Bacteria and Archaea

Cystic fibrosis (CF) is one of the most prevalent lethal genetic diseases with over 2000 identified mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Pharmacological chaperones such as Lumacaftor (VX-809), Tezacaftor (VX-661) and Elexacaftor (VX-445) treat mutation-induced defects by stabilizing CFTR and are called correctors. These correctors improve proper folding and thus facilitate processing and trafficking to increase the amount of functional CFTR on the cell surface. Yet, CFTR variants display differential responses to each corrector. Here, we report variants P67L and L206W respond similarly to VX-809 but divergently to VX-445 with P67L exhibiting little rescue when treated with VX-445. We investigate the underlying cellular mechanisms of how CFTR biogenesis is altered by correctors in these variants. Affinity purification-mass spectrometry (AP-MS) multiplexed with isobaric Tandem Mass Tags (TMT) was used to quantify CFTR protein-protein interaction changes between variants P67L and L206W. VX-445 facilitates unique proteostasis factor interactions especially in translation, folding, and degradation pathways in a CFTR variant-dependent manner. A number of these interacting proteins knocked down by siRNA, such as ribosomal subunit proteins, moderately rescued fully glycosylated P67L. Importantly, these knock-downs sensitize P67L to VX-445 and further enhance the correction of this variant. Our results provide a better understanding of VX-445 biological mechanism of action and reveal cellular targets that may sensitize unresponsive CFTR variants to known and available correctors.

/pdf/elexacaftor-vx-445-mediated-cftr-interactome-remodeling-2ispwrqx.pdf

Elexacaftor/VX-445-mediated CFTR interactome remodeling reveals differential correction driven by mutation-specific translational dynamics

Many cellular processes are governed by protein-protein interactions that require tight spatial and temporal regulation. Accordingly, it is necessary to understand the dynamics of protein interactions to fully comprehend and elucidate cellular processes and pathological disease states. To map de novo protein-protein interactions with time-resolution at an organelle-wide scale, we developed a quantitative mass-spectrometry method, time-resolved interactome profiling (TRIP). We apply TRIP to elucidate aberrant protein interaction dynamics that lead to the protein misfolding disease congenital hypothyroidism. We deconvolute altered temporal interactions of the thyroid hormone precursor thyroglobulin with pathways associated with hypothyroidism pathophysiology such as Hsp70/90 assisted folding, disulfide/redox processing, and N-glycosylation. Functional siRNA screening identified VCP and TEX264 as key protein degradation components whose inhibition selectively rescues mutant prohormone secretion. Ultimately, our results provide insight into the temporal coordination of protein homeostasis, and our TRIP method can have broad application in investigating protein folding diseases and cellular processes. HIGHLIGHTS Method to map de novo protein-protein interactions with temporal resolution Characterization of the time-resolved interactome of a protein folding disease state siRNA screening identifies VCP and TEX264 as major regulators of thyroglobulin processing VCP pharmacological inhibition rescues mutant thyroglobulin secretion

Time-Resolved Interactome Profiling Deconvolutes Secretory Protein Quality Control Dynamics

The study examines the effect of institutional and macro-economic variables on share prices of listed companies in Nepal. The dependent variables selected for the study are market price per share and market capitalization. The selected independent variables are earnings per share, dividend per share, price earnings ratio, GDP growth rate, interest rate and inflation rate. The study is based on secondary data of 12 commercial banks with 108 observations for the study period from 2014/15 to 2022/23. The data were collected from Banking and Financial Statistics published by Nepal Rastra Bank, publications and websites of Nepal Rastra Bank (NRB), Economic Survey Report published by Ministry of Finance and annual reports of the selected commercial banks. The correlation coefficients and regression models are estimated to test the significance and importance of institutional and macro-economic variables on share prices of Nepalese commercial banks. The study showed that earnings per share has a positive effect on market price per share and market capitalization. It means that increase in earnings per share leads to increase in market price per share and market capitalization. Similarly, dividend per share has a positive effect on market price per share and market capitalization. It means that increase in dividend per share leads to increase in market price per share and market capitalization. The results of the study also showed that price earnings ratio has a positive effect on market price per share and market capitalization. It implies that increase in price earnings ratio leads to increase in market price per share and market capitalization. Likewise, GDP growth rate has a positive effect on market price per share which indicates that higher GDP growth rate leads to increase in market price per share. However, interest rate has a negative effect on market price per share and market capitalization. It implies that higher interest rate leads to decrease in market price per share and market capitalization. Similarly, inflation rate has a positive effect on market price per share. It implies that higher inflation rate leads to increase in market price per share.

The Effect of Institutional and Macro-Economic Variables on Share Prices of Listed Companies in Nepal

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Papers

Comparative Genomics of Nitrogen Cycling Pathways in Bacteria and Archaea

Elexacaftor/VX-445-mediated CFTR interactome remodeling reveals differential correction driven by mutation-specific translational dynamics

Time-Resolved Interactome Profiling Deconvolutes Secretory Protein Quality Control Dynamics

The Effect of Institutional and Macro-Economic Variables on Share Prices of Listed Companies in Nepal