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• SOC bioavailability significantly differed among soil particle-size fractions. • SOC bioavailability of fine sand increased by 200 %, whereas clay reduced by 60 % • The porosity of fine sand was 60% of clay. • Abundances of soil elements of clay were 6–30 times higher than fine sand. • Microbial activity, mediated by soil morphology, affected SOC bioavailability. Despite the fact that physical and chemical processes have been widely proposed to explicate the stabilization mechanisms of soil organic carbon (SOC), thebioavailability of SOC linked to soil physical structure, microbial community structure, and functional genes remains poorly understood. This study aims to investigate the SOC division based on bioavailability differences formed by physical isolation, and to clarify the relationships of SOC bioavailability with soil elements, pore characteristics, and microbial activity. Results revealed that soil element abundances such as SOC, TN, and DOC ranked in the same order as the soil porosity as clay > silt ≥ coarse sand > fine sand in both top and sub soil. In contrast to silt and clay, which had reduced SOC bioavailability, fine sand and coarse sand had dramatically enhanced SOC bioavailability compared to the bulk soil. The bacterial and fungal community structure was significantly influenced by particle size, porosity, and soil elements. Copiotrophic bacteria and functional genes were more prevalent in fine sand than clay, which also contained more oligotrophic bacteria. The SOC bioavailability was positively correlated with abundances of functional genes, C degradation genes, and copiotrophic bacteria, but negatively correlated with abundances of soil elements, porosity, oligotrophic bacteria, and microbial biomass (p < 0.05). This indicated that the soil physical structure divided SOC into pools with varying levels of bioavailability, with sand fractions having more bioavailable organic carbon than finer fractions. Copiotrophic Proteobacteria and oligotrophic Acidobacteria, Firmicutes, and Gemmatimonadetes made up the majority of the bacteria linked to SOC mineralization. Additionally, the fungi Mortierellomycota and Mucoromycota, which are mostly involved in SOC mineralization, may have the potential for oligotrophic metabolism. Our results indicated that particle-size fractionation could influence the SOC bioavailability by restricting SOC accessibility and microbial activity, thus having a significant impact on sustaining soil organic carbon reserves in temperate agricultural ecosystems, and provided a new research direction for organic carbon stability. [ABSTRACT FROM AUTHOR]

A spindle-like hierarchical carbon structure of submicron dimensions is synthesized by floating catalytic deposition using a polyhydroxyalkanoate (PHA)/ferrocene/chloroform precursor. The electron microscopic morphology characterizations demonstrate that as-prepared carbon micro-spindle (CMS) comprises three components: two symmetric carbon cones formed by curved graphitic filaments consisted of randomly orientated graphene layers, and one middle catalyst plate with a rough surface. CMSs only grow on large catalyst plates with complicated surface microstructures. Chlorine is employed to tune the crystallinity of the catalyst, leading to a rough surface of the catalyst plate. Graphene layers are deposited parallel to the catalyst surface. Carbon spindles sharing the same catalyst plate form CMS clusters. The electrochemical performance of CMSs is further investigated, showing good capacitance properties with excellent cycling stability, indicating its application potential in energy storage devices. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Metformin is the most common treatment for type 2 diabetes (T2D). However, there have been no pharmacogenomic studies for T2D in which a population of color was used in the discovery analysis. This study sought to identify genomic variants associated with metformin response in African American patients with diabetes. RESEARCH DESIGN AND METHODS: Patients in the discovery set were adult, African American participants from the Diabetes Multi-omic Investigation of Drug Response (DIAMOND), a cohort study of patients with T2D from a health system serving southeast Michigan. DIAMOND participants had genome-wide genotype data and longitudinal electronic records of laboratory results and medication fills. The genome-wide discovery analysis identified polymorphisms correlated to changes in glycated hemoglobin (HbA1c) levels among individuals on metformin monotherapy. Lead associations were assessed for replication in an independent cohort of African American participants from Kaiser Permanente Northern California (KPNC) and in European American participants from DIAMOND. RESULTS: The discovery set consisted of 447 African American participants, whereas the replication sets included 353 African American KPNC participants and 466 European American DIAMOND participants. The primary analysis identified a variant, rs143276236, in the gene ARFGEF3, which met the threshold for genome-wide significance, replicated in KPNC African Americans, and was still significant in the meta-analysis (P = 1.17 × 10−9). None of the significant discovery variants replicated in European Americans DIAMOND participants. CONCLUSIONS: We identified a novel and biologically plausible genetic variant associated with a change in HbA1c levels among African American patients on metformin monotherapy. These results highlight the importance of diversity in pharmacogenomic studies. [ABSTRACT FROM AUTHOR]

Variability in response to short-acting β2-agonists (e.g., albuterol) among patients with asthma from diverse racial/ethnic groups may contribute to asthma disparities. We sought to identify genetic variants associated with bronchodilator response (BDR) to identify potential mechanisms of drug response and risk factors for worse asthma outcomes. Genome-wide association studies of bronchodilator response (BDR) were performed using TOPMed Whole Genome Sequencing data of the Asthma Translational Genomic Collaboration (ATGC), which corresponded to 1136 Puerto Rican, 656 Mexican and 4337 African American patients with asthma. With the population-specific GWAS results, a trans-ethnic meta-analysis was performed to identify BDR-associated variants shared across the three populations. Replication analysis was carried out in three pediatric asthma cohorts, including CAMP (Childhood Asthma Management Program; n = 560), GACRS (Genetics of Asthma in Costa Rica Study; n = 967) and HPR (Hartford-Puerto Rico; n = 417). A genome-wide significant locus (rs35661809; P = 3.61 × 10–8) in LINC02220, a non-coding RNA gene, was identified in Puerto Ricans. While this region was devoid of protein-coding genes, capture Hi-C data showed a distal interaction with the promoter of the DNAH5 gene in lung tissue. In replication analysis, the GACRS cohort yielded a nominal association (1-tailed P < 0.05). No genetic variant was associated with BDR at the genome-wide significant threshold in Mexicans and African Americans. Our findings help inform genetic underpinnings of BDR for understudied minority patients with asthma, but the limited availability of genetic data for racial/ethnic minority children with asthma remains a paramount challenge. [ABSTRACT FROM AUTHOR]

Genome-wide nucleotide composition varies widely among species. Despite extensive research, the source of genome-wide nucleotide composition diversity remains elusive. Yeast mitochondrial genomes (mitogenomes) are highly A + T rich, and they provide a unique opportunity to study the evolution of AT-biased landscape. In this study, we sequenced ten complete mitogenomes of the Saccharomycodes ludwigii yeast with 8% G + C content, the lowest genome-wide %(G + C) in all published genomes to date. The S. ludwigii mitogenomes have high densities of short tandem repeats but severely underrepresented mononucleotide repeats. Comparative population genomics of these record-setting A + T-rich genomes shows dynamic indel mutations and strong mutation bias toward A/T. Indel mutations play a greater role in genomic variation among very closely related strains than nucleotide substitutions. Indels have resulted in presence–absence polymorphism of tRNAArg (ACG) among S. ludwigii mitogenomes. Interestingly, these mitogenomes have undergone recombination, a genetic process that can increase G + C content by GC-biased gene conversion. Finally, the expected equilibrium G + C content under mutation pressure alone is higher than observed G + C content, suggesting existence of mechanisms other than AT-biased mutation operating to increase A/T. Together, our findings shed new lights on mechanisms driving extremely AT-rich genomes. [ABSTRACT FROM AUTHOR]

Background: Mitochondria support critical cellular functions, such as energy production through oxidative phosphorylation, regulation of reactive oxygen species, apoptosis, and calcium homeostasis. Objective: Given the heightened level of cellular activity in patients with asthma, we sought to determine whether mitochondrial DNA (mtDNA) copy number measured in peripheral blood differed between individuals with and without asthma. Methods: Whole genome sequence data was generated as part of the Trans-Omics for Precision Medicine (TOPMed) Program on participants from the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE) and the Study of African Americans, Asthma, Genes, & Environment II (SAGE II). We restricted our analysis to individuals who self-identified as African American (3,651 asthma cases and 1,344 controls). Mitochondrial copy number was estimated using the sequencing read depth ratio for the mitochondrial and nuclear genomes. Respiratory complex expression was assessed using RNA-sequencing. Results: Average mitochondrial copy number was significantly higher among individuals with asthma when compared with controls (SAPPHIRE: 218.60 vs. 200.47, P<0.001; SAGE II: 235.99 vs. 223.07, P<0.001). Asthma status was significantly associated with mitochondrial copy number after accounting for potential explanatory variables, such as participant age, sex, leukocyte counts, and mitochondrial haplogroup. Despite the consistent relationship between asthma status and mitochondrial copy number, the latter was not associated with time-to-exacerbation or patient-reported asthma control. Mitochondrial respiratory complex gene expression was disproportionately lower in individuals with asthma when compared with individuals without asthma and other protein-encoding genes. Conclusions: We observed a robust association between asthma and higher mitochondrial copy number. Asthma having an effect on mitochondria function was also supported by lower respiratory complex gene expression in this group. [ABSTRACT FROM AUTHOR]

Genome-wide significant loci for metformin response in type 2 diabetes reported elsewhere have not been replicated in the Diabetes Prevention Program (DPP). To assess pharmacogenetic interactions in prediabetes, we conducted a genome-wide association study (GWAS) in the DPP. Cox proportional hazards models tested associations with diabetes incidence in the metformin (MET; n = 876) and placebo (PBO; n = 887) arms. Multiple linear regression assessed association with 1-year change in metformin-related quantitative traits, adjusted for baseline trait, age, sex, and 10 ancestry principal components. We tested for gene-by-treatment interaction. No significant associations emerged for diabetes incidence. We identified four genome-wide significant variants after correcting for correlated traits (P < 9 × 10−9). In the MET arm, rs144322333 near ENOSF1 (minor allele frequency [MAF]AFR = 0.07; MAFEUR = 0.002) was associated with an increase in percentage of glycated hemoglobin (per minor allele, β = 0.39 [95% CI 0.28, 0.50]; P = 2.8 × 10−12). rs145591055 near OMSR (MAF = 0.10 in American Indians) was associated with weight loss (kilograms) (per G allele, β = −7.55 [95% CI −9.88, −5.22]; P = 3.2 × 10−10) in the MET arm. Neither variant was significant in PBO; gene-by-treatment interaction was significant for both variants [P(G×T) < 1.0 × 10−4]. Replication in individuals with diabetes did not yield significant findings. A GWAS for metformin response in prediabetes revealed novel ethnic-specific associations that require further investigation but may have implications for tailored therapy. [ABSTRACT FROM AUTHOR]

Although postoperative urinary retention (POUR) is common after spine surgery, the association of this adverse event with other morbidities and patient-reported outcomes is not fully understood. We sought to examine the sequelae of POUR after lumbar spine surgery. The Michigan Spine Surgery Improvement Collaborative (MSSIC) is a large prospective multicenter registry. MSSIC was queried with multivariate analysis for factors that are associated with POUR, the association of POUR with 90-day adverse events, and the effect of POUR on 2-year patient-reported outcomes and satisfaction. Multivariate analysis identified hardware revision (odds ratio [OR], 0.61), 1 operative level (OR, 0.74), and ambulation on postoperative day zero (OR, 0.65) to be protective for POUR. Factors associated with POUR included age (OR, 1.19), male gender (OR, 1.58), body mass index <25 (OR, 1.22), diabetes (OR, 1.28), coronary artery disease (OR, 1.20), fusion surgery (OR, 1.27), and longer surgery (OR, 1.11). Patients who had POUR were more likely to be readmitted, develop a urinary tract infection, and develop an infection (P < 0.001). POUR was associated with decreased likelihood of achieving Oswestry Disability Index minimal clinically important difference at 90 days (P < 0.001), but not at 1 year after surgery. POUR was associated with dissatisfaction with surgery at 90 days (P < 0.001), 1 year (P = 0.004), and 2 years after surgery (P = 0.011). POUR is common after lumbar spine surgery, and the demographic, diagnostic, and surgical factors that are associated with POUR are identified. POUR is associated with several adverse events, and patients who have POUR were less likely to be satisfied with surgery up to 2 years after surgery. [ABSTRACT FROM AUTHOR]

The Michigan Spine Surgery Improvement Collaborative is a statewide multicenter quality improvement registry. Because missing data can affect registry results, we used MSSIC to find demographic and surgical characteristics that affect the completion of patient-reported outcomes (PROs) at 90 days and 1 year. A total of 24,404 patients who had lumbar surgery (17,813 patients) or cervical surgery (6591 patients) were included. Multivariate logistic regression models of patient disease were constructed to identify risk factors for failure to complete scheduled PRO surveys. Patients ≥65 years old and female patients were both more likely to respond at 90 days and 1 year. Increasing education was associated with greater response rate at 90 days and 1 year. Whites and African Americans had no differences in response rates. Calling provided the highest response rate at 90 days and 1 year. For cervical spine patients, only discharge to rehabilitation increased completion rates, at 90 days but not 1 year. For lumbar spine patients, spondylolisthesis or stenosis (vs. herniated disc) had a greater response rate at 1 year. Patients with leg (vs. back) pain had a greater response only at 1 year. Patients with multilevel surgery had an increased response at 1 year. Patients who underwent fusion were more likely to respond at 90 days, but not 1 year. Discharge to rehabilitation increased response at 90 days and 1 year. A multivariate analysis from a multicenter prospective database identified surgical factors that affect PRO follow-up, up to 1 year. This information can be helpful for imputing missing PRO data and could be used to strengthen data derived from large prospective databases. [ABSTRACT FROM AUTHOR]

Graphene has been investigated and widely used as the high performance conductive additives in lithium ion batteries. Unfortunately, the LiFePO 4 batteries with graphene additives present quite a low rate performance because the graphene with planar structure blocks the Li ion transportation. Herein, a binary conductive additive containing only 1 wt% holey graphene (HG) and 1 wt% Carbon Black such as Super-P (SP) has been developed, which achieves excellent high-rate performance for the LiFePO 4 battery that is comparable to that of the battery with 10 wt% SP. The HG with large amount of holes and large specific surface area substantially enhances the electronic conductivity of LiFePO 4 electrode, but not compromises the high efficient ionic transportation. A small content of SP as the supplement of long-range conductive network formed by HG can contact the LiFePO 4 sufficiently for achieving excellent conductivity in the whole LiFePO 4 electrode. A balance of electronic conductivity and ionic diffusivity can be achieved using the HG and SP simultaneously. The HG and SP with low content can synergistically construct an excellent ionic and electronic conductive network in LiFePO 4 electrode. This study may promote the commercial applications of HG additives for high performance LiFePO 4 batteries. Image 1 [ABSTRACT FROM AUTHOR]

Urban agricultural soils can be an important reservoir of antibiotic resistance, and have great food safety and public health indications. This study investigated antibiotic-resistant bacteria and antibiotic resistance genes in urban agricultural soils using phenotypic and metagenomic tools. In total, 207 soil bacteria were recovered from 41 soil samples collected from an urban agricultural garden in Detroit, MI, USA. The most prevalent antibiotic resistance phenotype demonstrated by Gram-negative bacteria was resistance to ampicillin (94.2%), followed by chloramphenicol (80.0%), cefoxitin (79.5%), gentamicin (78.4%) and ceftriaxone (71.1%). All Gram-positive bacteria were resistant to gentamicin, kanamycin and penicillin. Genes encoding resistance to quinolones, β-lactams and tetracyclines were the most prevalent and abundant in the soil. qepA and tetA , both encoding efflux pumps, predominated in the quinolone and tetracycline resistance genes tested, respectively. Positive correlation ( P <0.05) was identified among groups of antibiotic resistance genes, and between antibiotic resistance genes and metal resistance genes. The data demonstrated a diverse population of antibiotic resistance in urban agricultural soils. Phenotypic determination together with soil metagenomics proved to be a valuable tool to study the nature and extent of antibiotic resistance in the environment. [ABSTRACT FROM AUTHOR]

The harmful effects of antibiotics on biological denitrification have attracted widespread attention due to their excessive usage. Polymyxin B (PMB) as the typical antimicrobial peptides having been regarded as the "last hope" for treatment of multidrug-resistance bacteria, has also been detected in wastewater. However, little is known about the influence of PMB on aerobic denitrification. In this study, the impact of PMB on aerobic denitrification performance was investigated. Results showed 0.50 mg/L PMB decreased nitrate removal efficiency from 97.4% to 85.3%, and drove denitrifiers to transform more nitrate to biomass instead of producing gas-N. The live/dead staining method showed PMB damaged bacterial membrane. Transcriptome analysis further indicated the key enzymes participating in denitrification and aerobic respiratory chains were suppressed by PMB. To resist the PMB stress, denitrifiers formed thicker biofilm to protect cells from PMB damaging and thus remodeling the central carbon metabolism. Further investigation revealed denitrifiers have different preference on various carbon sources when PMB is present. Subsequently, the underlying mechanism of the distinctive carbon sources preference was explored by the combination of transcriptome and metabolism analysis. Overall, our data suggested denitrifiers have distinctive carbon sources preference under PMB treatment conditions, reminding us that carbon source selection should be cautious in practical applications. [Display omitted] • PMB inhibits aerobic denitrification by directly repressing key enzymes expression. • Denitrifiers remodeled metabolism to form thicker biofilm to resist PMB stress. • Remolding metabolism caused distinct carbon source preference of denitrifiers. • Denitrifiers preferred carbohydrates when faced with PMB pressure. [ABSTRACT FROM AUTHOR]