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61 result(s) for "Blanton, John R."
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Whole blood transcriptomic analysis of beef cattle at arrival identifies potential predictive molecules and mechanisms that indicate animals that naturally resist bovine respiratory disease
Bovine respiratory disease (BRD) is a multifactorial disease complex and the leading infectious disease in post-weaned beef cattle. Clinical manifestations of BRD are recognized in beef calves within a high-risk setting, commonly associated with weaning, shipping, and novel feeding and housing environments. However, the understanding of complex host immune interactions and genomic mechanisms involved in BRD susceptibility remain elusive. Utilizing high-throughput RNA-sequencing, we contrasted the at-arrival blood transcriptomes of 6 beef cattle that ultimately developed BRD against 5 beef cattle that remained healthy within the same herd, differentiating BRD diagnosis from production metadata and treatment records. We identified 135 differentially expressed genes (DEGs) using the differential gene expression tools edgeR and DESeq2. Thirty-six of the DEGs shared between these two analysis platforms were prioritized for investigation of their relevance to infectious disease resistance using WebGestalt, STRING, and Reactome. Biological processes related to inflammatory response, immunological defense, lipoxin metabolism, and macrophage function were identified. Production of specialized pro-resolvin mediators (SPMs) and endogenous metabolism of angiotensinogen were increased in animals that resisted BRD. Protein-protein interaction modeling of gene products with significantly higher expression in cattle that naturally acquire BRD identified molecular processes involving microbial killing. Accordingly, identification of DEGs in whole blood at arrival revealed a clear distinction between calves that went on to develop BRD and those that resisted BRD. These results provide novel insight into host immune factors that are present at the time of arrival that confer protection from BRD.
Multipopulational transcriptome analysis of post-weaned beef cattle at arrival further validates candidate biomarkers for predicting clinical bovine respiratory disease
Bovine respiratory disease (BRD) remains the leading infectious disease in post-weaned beef cattle. The objective of this investigation was to contrast the at-arrival blood transcriptomes from cattle derived from two distinct populations that developed BRD in the 28 days following arrival versus cattle that did not. Forty-eight blood samples from two populations were selected for mRNA sequencing based on even distribution of development (n = 24) or lack of (n = 24) clinical BRD within 28 days following arrival; cattle which developed BRD were further stratified into BRD severity cohorts based on frequency of antimicrobial treatment: treated once (treated_1) or treated twice or more and/or died (treated_2+). Sequenced reads (~ 50 M/sample, 150 bp paired-end) were aligned to the ARS-UCD1.2 bovine genome assembly. One hundred and thirty-two unique differentially expressed genes (DEGs) were identified between groups stratified by disease severity (healthy, n = 24; treated_1, n = 13; treated_2+, n = 11) with edgeR (FDR ≤ 0.05). Differentially expressed genes in treated_1 relative to both healthy and treated_2+ were predicted to increase neutrophil activation, cellular cornification/keratinization, and antimicrobial peptide production. Differentially expressed genes in treated_2+ relative to both healthy and treated_1 were predicted to increase alternative complement activation, decrease leukocyte activity, and increase nitric oxide production. Receiver operating characteristic (ROC) curves generated from expression data for six DEGs identified in our current and previous studies ( MARCO, CFB, MCF2L, ALOX15, LOC100335828 (aka CD200R1 ) , and SLC18A2 ) demonstrated good-to-excellent (AUC: 0.800–0.899; ≥ 0.900) predictability for classifying disease occurrence and severity. This investigation identifies candidate biomarkers and functional mechanisms in at arrival blood that predicted development and severity of BRD.
Comprehensive at-arrival transcriptomic analysis of post-weaned beef cattle uncovers type I interferon and antiviral mechanisms associated with bovine respiratory disease mortality
Despite decades of extensive research, bovine respiratory disease (BRD) remains the most devastating disease in beef cattle production. Establishing a clinical diagnosis often relies upon visual detection of non-specific signs, leading to low diagnostic accuracy. Thus, post-weaned beef cattle are often metaphylactically administered antimicrobials at facility arrival, which poses concerns regarding antimicrobial stewardship and resistance. Additionally, there is a lack of high-quality research that addresses the gene-by-environment interactions that underlie why some cattle that develop BRD die while others survive. Therefore, it is necessary to decipher the underlying host genomic factors associated with BRD mortality versus survival to help determine BRD risk and severity. Using transcriptomic analysis of at-arrival whole blood samples from cattle that died of BRD, as compared to those that developed signs of BRD but lived (n = 3 DEAD, n = 3 ALIVE), we identified differentially expressed genes (DEGs) and associated pathways in cattle that died of BRD. Additionally, we evaluated unmapped reads, which are often overlooked within transcriptomic experiments. 69 DEGs (FDR<0.10) were identified between ALIVE and DEAD cohorts. Several DEGs possess immunological and proinflammatory function and associations with TLR4 and IL6. Biological processes, pathways, and disease phenotype associations related to type-I interferon production and antiviral defense were enriched in DEAD cattle at arrival. Unmapped reads aligned primarily to various ungulate assemblies, but failed to align to viral assemblies. This study further revealed increased proinflammatory immunological mechanisms in cattle that develop BRD. DEGs upregulated in DEAD cattle were predominantly involved in innate immune pathways typically associated with antiviral defense, although no viral genes were identified within unmapped reads. Our findings provide genomic targets for further analysis in cattle at highest risk of BRD, suggesting that mechanisms related to type I interferons and antiviral defense may be indicative of viral respiratory disease at arrival and contribute to eventual BRD mortality.
A Systems Biology Approach Using Transcriptomic Data Reveals Genes and Pathways in Porcine Skeletal Muscle Affected by Dietary Lysine
Nine crossbred finishing barrows (body weight 94.4 ± 6.7 kg) randomly assigned to three dietary treatments were used to investigate the effects of dietary lysine on muscle growth related metabolic and signaling pathways. Muscle samples were collected from the longissimus dorsi of individual pigs after feeding the lysine-deficient (4.30 g/kg), lysine-adequate (7.10 g/kg), or lysine-excess (9.80 g/kg) diet for five weeks, and the total RNA was extracted afterwards. Affymetrix Porcine Gene 1.0 ST Array was used to quantify the expression levels of 19,211 genes. Statistical ANOVA analysis of the microarray data showed that 674 transcripts were differentially expressed (at p ≤ 0.05 level); 60 out of 131 transcripts (at p ≤ 0.01 level) were annotated in the NetAffx database. Ingenuity pathway analysis showed that dietary lysine deficiency may lead to: (1) increased muscle protein degradation via the ubiquitination pathway as indicated by the up-regulated DNAJA1, HSP90AB1 and UBE2B mRNA; (2) reduced muscle protein synthesis via the up-regulated RND3 and ZIC1 mRNA; (3) increased serine and glycine synthesis via the up-regulated PHGDH and PSPH mRNA; and (4) increased lipid accumulation via the up-regulated ME1, SCD, and CIDEC mRNA. Dietary lysine excess may lead to: (1) decreased muscle protein degradation via the down-regulated DNAJA1, HSP90AA1, HSPH1, and UBE2D3 mRNA; and (2) reduced lipid biosynthesis via the down-regulated CFD and ME1 mRNA. Collectively, dietary lysine may function as a signaling molecule to regulate protein turnover and lipid metabolism in the skeletal muscle of finishing pigs.
The GFDL Global Ocean and Sea Ice Model OM4.0: Model Description and Simulation Features
We document the configuration and emergent simulation features from the Geophysical Fluid Dynamics Laboratory (GFDL) OM4.0 ocean/sea ice model. OM4 serves as the ocean/sea ice component for the GFDL climate and Earth system models. It is also used for climate science research and is contributing to the Coupled Model Intercomparison Project version 6 Ocean Model Intercomparison Project. The ocean component of OM4 uses version 6 of the Modular Ocean Model and the sea ice component uses version 2 of the Sea Ice Simulator, which have identical horizontal grid layouts (Arakawa C‐grid). We follow the Coordinated Ocean‐sea ice Reference Experiments protocol to assess simulation quality across a broad suite of climate‐relevant features. We present results from two versions differing by horizontal grid spacing and physical parameterizations: OM4p5 has nominal 0.5° spacing and includes mesoscale eddy parameterizations and OM4p25 has nominal 0.25° spacing with no mesoscale eddy parameterization. Modular Ocean Model version 6 makes use of a vertical Lagrangian‐remap algorithm that enables general vertical coordinates. We show that use of a hybrid depth‐isopycnal coordinate reduces the middepth ocean warming drift commonly found in pure z* vertical coordinate ocean models. To test the need for the mesoscale eddy parameterization used in OM4p5, we examine the results from a simulation that removes the eddy parameterization. The water mass structure and model drift are physically degraded relative to OM4p5, thus supporting the key role for a mesoscale closure at this resolution. Key Points Documentation is provided for a new generation of NOAA‐GFDL CMIP6/OMIP ocean ice climate models Dynamical core and physical parameterizations are described and key features of interannual CORE simulations are assessed Using hybrid vertical coordinates reduces spurious ocean heat drift
MONITORING AND UNDERSTANDING CHANGES IN EXTREMES
This scientific assessment examines changes in three climate extremes—extratropical storms, winds, and waves—with an emphasis on U.S. coastal regions during the cold season. There is moderate evidence of an increase in both extratropical storm frequency and intensity during the cold season in the Northern Hemisphere since 1950, with suggestive evidence of geographic shifts resulting in slight upward trends in offshore/coastal regions. There is also suggestive evidence of an increase in extreme winds (at least annually) over parts of the ocean since the early to mid-1980s, but the evidence over the U.S. land surface is inconclusive. Finally, there is moderate evidence of an increase in extreme waves in winter along the Pacific coast since the 1950s, but along other U.S. shorelines any tendencies are of modest magnitude compared with historical variability. The data for extratropical cyclones are considered to be of relatively high quality for trend detection, whereas the data for extreme winds and waves are judged to be of intermediate quality. In terms of physical causes leading to multidecadal changes, the level of understanding for both extratropical storms and extreme winds is considered to be relatively low, while that for extreme waves is judged to be intermediate. Since the ability to measure these changes with some confidence is relatively recent, understanding is expected to improve in the future for a variety of reasons, including increased periods of record and the development of “climate reanalysis” projects.
The GFDL Earth System Model Version 4.1 (GFDL‐ESM 4.1): Overall Coupled Model Description and Simulation Characteristics
We describe the baseline coupled model configuration and simulation characteristics of GFDL's Earth System Model Version 4.1 (ESM4.1), which builds on component and coupled model developments at GFDL over 2013–2018 for coupled carbon‐chemistry‐climate simulation contributing to the sixth phase of the Coupled Model Intercomparison Project. In contrast with GFDL's CM4.0 development effort that focuses on ocean resolution for physical climate, ESM4.1 focuses on comprehensiveness of Earth system interactions. ESM4.1 features doubled horizontal resolution of both atmosphere (2° to 1°) and ocean (1° to 0.5°) relative to GFDL's previous‐generation coupled ESM2‐carbon and CM3‐chemistry models. ESM4.1 brings together key representational advances in CM4.0 dynamics and physics along with those in aerosols and their precursor emissions, land ecosystem vegetation and canopy competition, and multiday fire; ocean ecological and biogeochemical interactions, comprehensive land‐atmosphere‐ocean cycling of CO2, dust and iron, and interactive ocean‐atmosphere nitrogen cycling are described in detail across this volume of JAMES and presented here in terms of the overall coupling and resulting fidelity. ESM4.1 provides much improved fidelity in CO2 and chemistry over ESM2 and CM3, captures most of CM4.0's baseline simulations characteristics, and notably improves on CM4.0 in (1) Southern Ocean mode and intermediate water ventilation, (2) Southern Ocean aerosols, and (3) reduced spurious ocean heat uptake. ESM4.1 has reduced transient and equilibrium climate sensitivity compared to CM4.0. Fidelity concerns include (1) moderate degradation in sea surface temperature biases, (2) degradation in aerosols in some regions, and (3) strong centennial scale climate modulation by Southern Ocean convection. Plain Language Summary GFDL has developed a coupled chemistry‐carbon‐climate Earth System Model (ESM4.1) as part of its fourth‐generation coupled model development activities with model results contributed publicly to the sixth phase of the Coupled Model Intercomparison Project. With similar computational expense as GFDL's first coupled model CM4.0, ESM4.1 focuses on chemistry and ecosystem comprehensiveness rather than the ocean resolution‐focus of CM4.0. With fidelity near to that of CM4.0, ESM4.1 features much improved representation of climate mean patterns and variability from previous GFDL ESMs as well as comprehensive couplings for chemistry, carbon, and dust. Key Points A new coupled chemistry‐carbon‐climate Earth system model has been developed at the Geophysical Fluid Dynamics Laboratory This model unifies component advances in chemistry, carbon, and ecosystem comprehensiveness within a single coupled climate framework This model features much improved climate mean patterns and variability from previous chemistry and carbon coupled models
A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (LIBERATE)
This is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of Zephyr Endobronchial Valve (EBV) in patients with little to no collateral ventilation out to 12 months. To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation in the treated lobe. Subjects were enrolled with a 2:1 randomization (EBV/standard of care [SoC]) at 24 sites. Primary outcome at 12 months was the ΔEBV-SoC of subjects with a post-bronchodilator FEV improvement from baseline of greater than or equal to 15%. Secondary endpoints included absolute changes in post-bronchodilator FEV , 6-minute-walk distance, and St. George's Respiratory Questionnaire scores. A total of 190 subjects (128 EBV and 62 SoC) were randomized. At 12 months, 47.7% EBV and 16.8% SoC subjects had a ΔFEV greater than or equal to 15% (P < 0.001). ΔEBV-SoC at 12 months was statistically and clinically significant: for FEV , 0.106 L (P < 0.001); 6-minute-walk distance, +39.31 m (P = 0.002); and St. George's Respiratory Questionnaire, -7.05 points (P = 0.004). Significant ΔEBV-SoC were also observed in hyperinflation (residual volume, -522 ml; P < 0.001), modified Medical Research Council Dyspnea Scale (-0.8 points; P < 0.001), and the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index (-1.2 points). Pneumothorax was the most common serious adverse event in the treatment period (procedure to 45 d), in 34/128 (26.6%) of EBV subjects. Four deaths occurred in the EBV group during this phase, and one each in the EBV and SoC groups between 46 days and 12 months. Zephyr EBV provides clinically meaningful benefits in lung function, exercise tolerance, dyspnea, and quality of life out to at least 12 months, with an acceptable safety profile in patients with little or no collateral ventilation in the target lobe. Clinical trial registered with www.clinicaltrials.gov (NCT 01796392).
Remote sensing-based assessment of mangrove ecosystems in the Gulf Cooperation Council countries: a systematic review
Mangrove forests in the Gulf Cooperation Council (GCC) countries are facing multiple threats from natural and anthropogenic-driven land use change stressors, contributing to altered ecosystem conditions. Remote sensing tools can be used to monitor mangroves, measure mangrove forest-and-tree-level attributes and vegetation indices at different spatial and temporal scales that allow a detailed and comprehensive understanding of these important ecosystems. Using a systematic literature approach, we reviewed 58 remote sensing-based mangrove assessment articles published from 2010 through 2022. The main objectives of the study were to examine the extent of mangrove distribution and cover, and the remotely sensed data sources used to assess mangrove forest/tree attributes. The key importance of and threats to mangroves that were specific to the region were also examined. Mangrove distribution and cover were mainly estimated from satellite images (75.2%), using NDVI (Normalized Difference Vegetation Index) derived from Landsat (73.3%), IKONOS (15%), Sentinel (11.7%), WorldView (10%), QuickBird (8.3%), SPOT-5 (6.7%), MODIS (5%) and others (5%) such as PlanetScope. Remotely sensed data from aerial photographs/images (6.7%), LiDAR (Light Detection and Ranging) (5%) and UAV (Unmanned Aerial Vehicles)/Drones (3.3%) were the least used. Mangrove cover decreased in Saudi Arabia, Oman, Bahrain, and Kuwait between 1996 and 2020. However, mangrove cover increased appreciably in Qatar and remained relatively stable for the United Arab Emirates (UAE) over the same period, which was attributed to government conservation initiatives toward expanding mangrove afforestation and restoration through direct seeding and seedling planting. The reported country-level mangrove distribution and cover change results varied between studies due to the lack of a standardized methodology, differences in satellite imagery resolution and classification approaches used. There is a need for UAV-LiDAR ground truthing to validate country-and-local-level satellite data. Urban development-driven coastal land reclamation and pollution, climate change-driven temperature and sea level rise, drought and hypersalinity from extreme evaporation are serious threats to mangrove ecosystems. Thus, we encourage the prioritization of mangrove conservation and restoration schemes to support the achievement of related UN Sustainable Development Goals (13 climate action, 14 life below water, and 15 life on land) in the GCC countries.
Non-mumps Viral Parotitis During the 2014-2015 Influenza Season in the United States
We investigated a multistate outbreak of acute viral non-mumps parotitis (NMP). Understanding epidemiologic and clinical features of viral NMP might improve diagnostic acumen among clinicians considering illnesses that could be mumps, resulting in more timely treatment and public health action. Abstract Background During the 2014-2015 US influenza season, 320 cases of non-mumps parotitis (NMP) among residents of 21 states were reported to the Centers for Disease Control and Prevention (CDC). We conducted an epidemiologic and laboratory investigation to determine viral etiologies and clinical features of NMP during this unusually large occurrence. Methods NMP was defined as acute parotitis or other salivary gland swelling of >2 days duration in a person with a mumps- negative laboratory result. Using a standardized questionnaire, we collected demographic and clinical information. Buccal samples were tested at the CDC for selected viruses, including mumps, influenza, human parainfluenza viruses (HPIVs) 1-4, adenoviruses, cytomegalovirus, Epstein-Barr virus (EBV), herpes simplex viruses (HSVs) 1 and 2, and human herpes viruses (HHVs) 6A and 6B. Results Among the 320 patients, 65% were male, median age was 14.5 years (range, 0-90), and 67% reported unilateral parotitis. Commonly reported symptoms included sore throat (55%) and fever (48%). Viruses were detected in 210 (71%) of 294 NMP patients with adequate samples for testing, ≥2 viruses were detected in 37 samples, and 248 total virus detections were made among all samples. These included 156 influenza A(H3N2), 42 HHV6B, 32 EBV, 8 HPIV2, 2 HPIV3, 3 adenovirus, 4 HSV-1, and 1 HSV-2. Influenza A(H3N2), HHV6B, and EBV were the most frequently codetected viruses. Conclusions Our findings suggest that, in addition to mumps, clinicians should consider respiratory viral (influenza) and herpes viral etiologies for parotitis, particularly among patients without epidemiologic links to mumps cases or outbreaks.