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270 records · Page 15

Genetic Predictive Factors for Nonsusceptible Phenotypes and Multidrug Resistance in Expanded-Spectrum Cephalosporin-Resistant Uropathogenic Escherichia coli from a Multicenter Cohort: Insights into the Phenotypic and Genetic Basis of Coresistance

Antimicrobial resistance in urinary tract infections (UTIs) is a major public health concern. This study aims to characterize the phenotypic and genetic basis of multidrug resistance (MDR) among expanded-spectrum cephalosporin-resistant (ESCR) uropathogenic Escherichia coli (UPEC) causing UTIs in California patient populations. Between February and October 2019, 577 ESCR UPEC isolates were collected from patients at 6 clinical laboratory sites across California. Lineage and antibiotic resistance genes were determined by analysis of whole-genome sequence data. The lineages ST131, ST1193, ST648, and ST69 were predominant, representing 46%, 5.5%, 4.5%, and 4.5% of the collection, respectively. Overall, 527 (91%) isolates had an expanded-spectrum β-lactamase (ESBL) phenotype, with bla CTX-M-15 , bla CTX-M-27 , bla CTX-M-55 , and bla CTX-M-14 being the most prevalent ESBL genes. In the 50 non-ESBL phenotype isolates, 40 (62%) contained bla CMY-2 , which was the predominant plasmid-mediated AmpC (pAmpC) gene. Narrow-spectrum β-lactamases, bla TEM-1B and bla OXA-1 , were also found in 44.9% and 32.1% of isolates, respectively. Among ESCR UPEC isolates, isolates with an ESBL phenotype had a 1.7-times-greater likelihood of being MDR than non-ESBL phenotype isolates (P < 0.001). The cooccurrence of bla CTX-M-15 , bla OXA-1 , and aac(6')-Ib-cr within ESCR UPEC isolates was strongly correlated. Cooccurrence of bla CTX-M-15 , bla OXA-1 , and aac(6')-Ib-cr was associated with an increased risk of nonsusceptibility to piperacillin-tazobactam, cefepime, fluoroquinolones, and amikacin as well as MDR. Multivariate regression revealed the presence of bla CTX-M-55 , bla TEM-1B , and the ST131 genotype as predictors of MDR.

59 BASIC BIOLOGICAL SCIENCES↗

Ergot alkaloid consumption alters serotonin receptor-induced vasoactivity in ovine umbilical vasculature

Consumption of ergot alkaloids during the second half of gestation has been shown to decrease umbilical artery vasoactivity resulting in decreased birth weights. Negative vascular effects of ergot alkaloids are mediated predominantly through serotonergic and adrenergic receptors in other tissues. Vasoactivity of serotonin (5-HT) receptors 5-HT 2A and 5-HT 1B/1D in umbilical artery and vein from ewes receiving endophyte-infected seed (E + 1.77 mg ergovaline/hd/d) or a control total mixed ration (CON; 0 mg ergovaline/hd/d) tall fescue seed at d-110 and d-133 of gestation was evaluated. Gravid reproduction tracts were collected from ewes. Two-mm sections of umbilical artery and vein were exposed to increasing concentrations of a 5-HT 1B/1D agonist and 5-HT 2A agonist. The 5-HT 1B/1D agonist did not stimulate a contractile response in artery or vein or either gestation time point. 5-HT 2A agonist caused large responses in artery with greatest occurring at d-110 and decreasing in magnitude as days of gestation increased ( p < 0.05). On d-110 and 133 of gestation, arteries from CON ewes had greater contractile response than arteries collected from E+ ewes ( p < 0.05). Veins responded to increasing concentrations of the 5-HT 2A agonist. Maximal d-110 vein response was greater than d-133 when exposed to 5-HT 2A agonist ( p < 0.05). Unlike the artery, veins from E+ ewes had greater d-133 contractile response than CON ( p < 0.05). Vascular contractions of umbilical artery and vein are induced by 5-HT 2A receptor activity and not 5-HT 1B/1D . Umbilical artery 5-HT 2A receptor activity was more sensitive to seed treatment and could be responsible for ergot alkaloid-induced intra-uterine growth restriction.

Toxicology↗

The endocannabinoid system in bovine tissues: characterization of transcript abundance in the growing Holstein steer

Abstract Background The endocannabinoid system (ECS) is highly integrated with seemingly all physiological and pathophysiological processes in the body. There is increasing interest in utilizing bioactive plant compounds, for promoting health and improving production in livestock. Given the established interaction between phytochemicals and the ECS, there are many opportunities for identification and development of therapies to address a range of diseases and disorders. However, the ECS has not been thoroughly characterized in cattle, especially in the gastrointestinal tract. The objective of this study was to characterize the distribution and transcriptional abundance of genes associated with the endocannabinoid system in bovine tissues. Methods Tissues including brain, spleen, thyroid, lung, liver, kidney, mesenteric vein, tongue, sublingual mucosa, rumen, omasum, duodenum, jejunum, ileum and colon were collected from 10-mo old Holstein steers (n = 6). Total RNA was extracted and gene expression was measured using absolute quantification real time qPCR. Gene expression of endocannabinoid receptorsCNR1andCNR2, synthesis enzymesDAGLA,DAGLBandNAPEPLD, degradation enzymesMGLLandFAAH, and transient receptor potential vanilloidsTRPV3andTRPV6was measured. Data were analyzed in R using a Kruskal-Wallis followed by a Wilcoxon rank-sum test. Results are reported as the median copy number/20 ng of equivalent cDNA (CN) with interquartile range (IQR). Results The greatest expression ofCNR1andCNR2was in the brain and spleen, respectively. Expression of either receptor was not detected in any gastrointestinal tissues, however there was a tendency (P = 0.095) forCNR2to be expressed above background in rumen. Expression of endocannabinoid synthesis and degradation enzymes varied greatly across tissues. Brain tissue had the greatestDAGLAexpression at 641 CN (IQR 52;P ≤ 0.05).DAGLBwas detected in all tissues, with brain and spleen having the greatest expression (P ≤ 0.05). Expression ofNAPEPLDin the gastrointestinal tract was lowest in tongue and sublingual mucosal. There was no difference in expression ofNAPEPLDbetween hindgut tissues, however these tissues collectively had 592% greater expression than rumen and omasum (P ≤ 0.05). WhileMGLLwas found to be expressed in all tissues, expression ofFAAHwas only above the limit of detection in brain, liver, kidney, jejunum and ileum.TRPV3was expressed above background in tongue, rumen, omasum and colon. Although not different from each other, thyroid and duodenum had the greatest expression ofTRPV6, with 285 (IQR 164) and 563 (IQR 467) CN compared to all other tissues (P < 0.05). Conclusions These data demonstrate the complex distribution and variation of the ECS in bovine tissues. Expression patterns suggest that regulatory functions of this system are tissue dependent, providing initial insight into potential target tissues for manipulation of the ECS.

Veterinary Sciences↗

A vision of immuno-oncology: the Siena think tank of the Italian Network for Tumor Biotherapy (NIBIT) foundation

The yearly Think Tank Meeting of the Italian Network for Tumor Biotherapy (NIBIT) Foundation, brings together in Siena, Tuscany (Italy), experts in immuno-oncology to review the learnings from current immunotherapy treatments, and to propose new pre-clinical and clinical investigations in selected research areas. While immunotherapies in non-small cell lung cancer and melanoma led to practice changing therapies, the same therapies had only modest benefit for patients with other malignancies, such as mesothelioma and glioblastoma. One way to improve on current immunotherapies is to alter the sequence of each combination agent. Matching the immunotherapy to the host’s immune response may thus improve the activity of the current treatments. A second approach is to combine current immunotherapies with novel agents targeting complementary mechanisms. Identifying the appropriate novel agents may require different approaches than the traditional laboratory-based discovery work. For example, artificial intelligence-based research may help focusing the search for innovative and most promising combination partners. Novel immunotherapies are needed in cancer patients with resistance to or relapse after current immunotherapeutic drugs. Such new treatments may include targeted agents or monoclonal antibodies to overcome the immune-suppressive tumor microenvironment. The mode of combining the novel treatments, including vaccines, needs to be matched to the patient’s immune status for achieving the maximum benefit. In this scenario, specific attention should be also paid nowadays to the immune intersection between COVID-19 and cancer.

60 APPLIED LIFE SCIENCES↗

Utah FORGE - Development of a Reservoir Seismic Velocity Model and Seismic Resolution Study

This is data from and a final report on the development of a 3D velocity model for the larger FORGE area and on the seismic resolution in the stimulated fracture volume at the bottom of well 16A-32. The velocity model was developed using RMS velocities of the seismic reflection survey and seismic velocity logs from borehole measurements as an input model. To improve the accuracy of the model in the shallow subsurface, travel times phase arrivals of the direct propagating P-waves were determined from the seismic reflection data, using PhaseNet, a deep-neural-network-based seismic arrival time picking method. The travel times were subsequently inverted using the input velocity model. The seismic resolution study used borehole and surface seismic sensors as well as the seismicity observed during the April 2022 stimulation experiment to estimate the seismic resolution in the activated fracture reservoir. The data contain a 3D P- and S-wave velocity model for the larger FORGE area.

15 GEOTHERMAL ENERGY↗

Very High-Resolution Satellite-Derived Bathymetry and Habitat Mapping Using Pleiades-1 and ICESat-2

Accurate and reliable bathymetric data are needed for a wide diversity of marine research and management applications. Satellite-derived bathymetry represents a time saving method to map large shallow waters of remote regions compared to the current costly in situ measurement techniques. This study aims to create very high-resolution (VHR) bathymetry and habitat mapping in Mayotte island waters (Indian Ocean) by fusing 0.5 m Pleiades-1 passive multispectral imagery and active ICESat-2 LiDAR bathymetry. ICESat-2 georeferenced photons were filtered to remove noise and corrected for water column refraction. The bathymetric point clouds were validated using the French naval hydrographic and oceanographic service Litto3D® dataset and then used to calibrate the multispectral image to produce a digital depth model (DDM). The latter enabled the creation of a digital albedo model used to classify benthic habitats. ICESat-2 provided bathymetry down to 15 m depth with a vertical accuracy of bathymetry estimates reaching 0.89 m. The benthic habitats map produced using the maximum likelihood supervised classification provided an overall accuracy of 96.62%. This study successfully produced a VHR DDM solely from satellite data. Digital models of higher accuracy were further discussed in the light of the recent and near-future launch of higher spectral and spatial resolution satellites.

Bathymetry↗

Guatemala and Panama Urban Development: Evaluating the Effects of Urban Expansion on Social and Environmental Vulnerability in Guatemala and Panama

Central America is experiencing rapid and unregulated urban expansion, which is contributing to an increase in socioeconomic and environmental risks including inequities in infrastructure and housing accessibility, biodiversity loss, vulnerability to natural disasters, and negative health outcomes. NASA DEVELOP, in partnership with NASA SERVIR, Sistema de la Integración Centroamericana (SICA), Secretariat of Central American Social Integration (SISCA), Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ), and Centro de Coordinación para la Prevención de los Desastres en América Central y República Dominicana (CEPRENEDAC), examined changes in urban extent, characterized roofing material type, and analyzed vulnerability within urban areas in two Central American cities, Guatemala City and Panama City. The team used land cover imagery from Landsat 5 Thematic Mapper (TM), Landsat 7 Enhanced Thematic Mapper Plus (ETM+), Landsat 8 Operational Land Imager (OLI), and Landsat 9 OLI-2 to map urban extent, and surface reflectance data from Maxar Worldview to identify roofing material types. Socioeconomic and environmental data were used to assess vulnerability. Results depict how the two cities have expanded from 2000 to present day and highlight areas of greatest vulnerability within each urban area. The supervised classification of roofing materials performed well but could be improved with a few enhancements. Findings can help partner organizations improve monitoring of urbanization and inform their planning and decision-making while prioritizing disaster prevention, public health, and environmental integrity. Additionally, these case studies can be used to inform future, similar work elsewhere in Central America to aid in understanding urbanization and its associated challenges.

Jennifer Ruiz↗

Evaluating the Effects of Urban Expansion on Social and Environmental Vulnerability in Guatemala and Panama

Central America is one of the fastest urbanizing regions in the world, with the urban population expected to double by 2050. This growth is driving multiple societal issues, including infrastructure inequities, lack of accessible housing, and environmental degradation. This project partnered with NASA SERVIR, Sistema de la Integración Centroamericana (SICA), Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ), and Centro de Coordinación para la Prevención de los Desastres en América Central y República Dominicana (CEPRENEDAC) to examine changes in urban extent and vulnerability in Guatemala City, Guatemala and Panama City, Panama. The team identified urban extent using Landsat 7 Enhanced Thematic Mapper Plus (ETM+), Landsat 8 Operational Land Imager (OLI), and Landsat 9 OLI-2 within Google Earth Engine’s LandTrendr algorithm. Next, they assessed urban vulnerability between formal and informal settlements by classifying different types of roof material using high-resolution Maxar Worldview 2 and 3 imagery and comparing it to socioeconomic and environmental risks. While both cities have expanded outward and become denser since 2000, Guatemala City has grown at a faster rate. The most vulnerable communities of both cities were located in the northwestern regions. These case studies can be used to inform similar methodologies in other Central American cities and help leaders identify the most vulnerable communities within their areas.

Aaron Whittemore↗