Carbon Amendments Influence Composition and Functional Capacities of Indigenous Soil Microbiomes

Soil nutrient amendments are recognized for their potential to improve microbial activity and biomass in the soil. However, the specific selective impacts of carbon amendments on indigenous microbiomes and their metabolic functions in agricultural soils remain poorly understood. We investigated the changes in soil chemical characteristics and phenotypes of Streptomyces communities following carbon amendments to soil. Mesocosms were established with soil from two field sites varying in soil organic matter content (low organic matter, LOM; high organic matter, HOM), that were amended at intervals over nine months with low or high dose solutions of glucose, fructose, malic acid, a mixture of these compounds, or water only (non-amended control). Significant shifts in soil chemical characteristics and antibiotic inhibitory capacities of indigenous Streptomyces were observed in response to carbon additions. All high dose carbon amendments consistently increased soil total carbon, while amendments with malic acid decreased soil pH. In LOM soils, higher frequencies of Streptomyces inhibitory phenotypes of the two plant pathogens, Streptomyces scabies and Fusarium oxysporum, were observed in response to soil carbon additions. Additionally, to determine if shifts in Streptomyces functional characteristics correlated with microbiome composition, we investigated whether shifts in functional characteristics of soil Streptomyces correlated with composition of soil bacterial communities, analyzed using 16S rRNA gene sequencing. Regardless of dose, community composition differed significantly among carbon-amended and non-amended soils from both sites. Carbon type and dose had significant effects on bacterial community composition in both LOM and HOM soils. Relationships among microbial community richness (observed species number), diversity, and soil characteristics varied among soils from different sites. These results suggest that manipulation of soil resource availability has the potential to selectively modify the functional capacities of soil microbiomes, and specifically to enhance pathogen inhibitory populations of high value to agricultural systems

Assessing Nutrient Limitation in Complex Forested Ecosystems : Alternatives to Large-Scale Fertilization Experiments

Quantifying nutrient limitation of primary productivity is a fundamental task of terrestrial ecosystem ecology, but in a high carbon dioxide environment it is even more critical that we understand potential nutrient constraints on plant growth. Ecologists often manipulate nutrients with fertilizer to assess nutrient limitation, yet for a variety of reasons, nutrient fertilization experiments are either impractical or incapable of resolving ecosystem responses to some global changes. The challenges of conducting large, in situ fertilization experiments are magnified in forests, especially the high-diversity forests common throughout the lowland tropics. A number of methods, including fertilization experiments, could be seen as tools in a toolbox that ecologists may use to attempt to assess nutrient limitation, but there has been no compilation or synthetic discussion of those methods in the literature. Here, we group these methods into one of three categories (indicators of soil nutrient supply, organismal indicators of nutrient limitation, and lab-based experiments and nutrient depletions), and discuss some of the strengths and limitations of each. Next, using a case study, we compare nutrient limitation assessed using these methods to results obtained using large-scale fertilizations across the Hawaiian Archipelago. We then explore the application of these methods in high-diversity tropical forests. In the end, we suggest that, although no single method is likely to predict nutrient limitation in all ecosystems and at all scales, by simultaneously utilizing a number of the methods we describe, investigators may begin to understand nutrient limitation in complex and diverse ecosystems such as tropical forests. In combination, these methods represent our best hope for understanding nutrient constraints on the global carbon cycle, especially in tropical forest ecosystems

Associating Social Determinants of Health With PROMIS CAT Scores and Health Care Utilization After ACL Reconstruction

BACKGROUND: The term social determinants of health (SDOH) refers to social and economic factors that influence a patient\u27s health status. The effect of SDOH on the Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive test (CAT) scores and postoperative resource utilization in patients with anterior cruciate ligament reconstruction (ACLR) have yet to be thoroughly studied. PURPOSE: To investigate the impact SDOH have on PROMIS CAT outcomes and postoperative resource utilization in patients with ACLR. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The electronic medical record was used to identify the SDOH for patients who underwent ACLR by 1 of 3 sports medicine fellowship-trained orthopaedic surgeons between July 2017 and April 2020. PROMIS CAT measures of Physical Function (PROMIS-PF), Pain Interference (PROMIS-PI), and Depression (PROMIS-D) were completed at the preoperative, 6-month postoperative, and 12-month postoperative time points. Postoperative health care utilization was recorded as well. Independent 2-group t tests and Wilcoxon rank-sum tests were used to analyze mean differences between patient groups based on SDOH. RESULTS: Two-hundred and thirty patients who underwent ACLR were included (mean age, 27 years; 59% male). Compared with White patients, Black patients were represented more frequently in the lowest median household income (MHI) quartile (63% vs 23%, respectively; P \u3c .001). White patients were represented more frequently in the highest area deprivation index (ADI) quartile when compared with Black patients (67% vs 12%, respectively; P = .006). Significantly worse PROMIS-PF, PROMIS-PI, and PROMIS-D scores at all 3 time points were found among patients who were Black, female, smokers, and in the lower MHI quartiles, with higher ADI and public health care coverage. In terms of resource utilization, Black patients attended significantly fewer postoperative physical therapy visits when compared with their respective counterparts. Those in the lower MHI quartiles attended significantly fewer postoperative imaging encounters, and female patients attended significantly more postoperative virtual encounters than male patients. CONCLUSION: Specific SDOH variables, particularly those that reflect racial and socioeconomic disparities, were associated with differences in postoperative health care utilization and ACLR outcomes as measured by PROMIS CAT domains

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

A Novel Conserved Isoform of the Ubiquitin Ligase UFD2a/UBE4B Is Expressed Exclusively in Mature Striated Muscle Cells

Yeast Ufd2p was the first identified E4 multiubiquitin chain assembly factor. Its vertebrate homologues later referred to as UFD2a, UBE4B or E4B were also shown to have E3 ubiquitin ligase activity. UFD2a function in the brain has been well established in vivo, and in vitro studies have shown that its activity is essential for proper condensation and segregation of chromosomes during mitosis. Here we show that 2 alternative splice forms of UFD2a, UFD2a-7 and -7/7a, are expressed sequentially during myoblast differentiation of C2C12 cell cultures and during cardiotoxin-induced regeneration of skeletal muscle in mice. UFD2a-7 contains an alternate exon 7, and UFD2a-7/7a, the larger of the 2 isoforms, contains an additional novel exon 7a. Analysis of protein or mRNA expression in mice and zebrafish revealed that a similar pattern of isoform switching occurs during developmental myogenesis of cardiac and skeletal muscle. In vertebrates (humans, rodents, zebrafish), UFD2a-7/7a is expressed only in mature striated muscle. This unique tissue specificity is further validated by the conserved presence of 2 muscle-specific splicing regulatory motifs located in the 3′ introns of exons 7 and 7a. UFD2a interacts with VCP/p97, an AAA-type ATPase implicated in processes whose functions appear to be regulated, in part, through their interaction with one or more of 15 previously identified cofactors. UFD2a-7/7a did not interact with VCP/p97 in yeast 2-hybrid experiments, which may allow the ATPase to bind cofactors that facilitate its muscle-specific functions. We conclude that the regulated expression of these UFD2a isoforms most likely imparts divergent functions that are important for myogenisis

Consensus Recommendations for the Use of Automated Insulin Delivery (AID) Technologies in Clinical Practice

International audienceThe significant and growing global prevalence of diabetes continues to challenge people with diabetes (PwD), healthcare providers and payers. While maintaining near-normal glucose levels has been shown to prevent or delay the progression of the long-term complications of diabetes, a significant proportion of PwD are not attaining their glycemic goals. During the past six years, we have seen tremendous advances in automated insulin delivery (AID) technologies. Numerous randomized controlled trials and real-world studies have shown that the use of AID systems is safe and effective in helping PwD achieve their long-term glycemic goals while reducing hypoglycemia risk. Thus, AID systems have recently become an integral part of diabetes management. However, recommendations for using AID systems in clinical settings have been lacking. Such guided recommendations are critical for AID success and acceptance. All clinicians working with PwD need to become familiar with the available systems in order to eliminate disparities in diabetes quality of care. This report provides much-needed guidance for clinicians who are interested in utilizing AIDs and presents a comprehensive listing of the evidence payers should consider when determining eligibility criteria for AID insurance coverage