RESUMEN
Rates of microbial processes are fundamental to understanding the significance of microbial impacts on environmental chemical cycling. However, it is often difficult to quantify rates or to link processes to specific taxa or individual cells, especially in environments where there are few cultured representatives with known physiology. Here, we describe the use of the redox-enzyme-sensitive molecular probe RedoxSensor™ Green to measure rates of anaerobic electron transfer physiology (i.e., sulfate reduction and methanogenesis) in individual cells and link those measurements to genomic sequencing of the same single cells. We used this method to investigate microbial activity in hot, anoxic, low-biomass (~103 cells mL-1) groundwater of the Death Valley Regional Flow System, California. Combining this method with electron donor amendment experiments and metatranscriptomics confirmed that the abundant spore formers including Candidatus Desulforudis audaxviator were actively reducing sulfate in this environment, most likely with acetate and hydrogen as electron donors. Using this approach, we measured environmental sulfate reduction rates at 0.14 to 26.9 fmol cell-1 h-1. Scaled to volume, this equates to a bulk environmental rate of ~103 pmol sulfate L-1 d-1, similar to potential rates determined with radiotracer methods. Despite methane in the system, there was no evidence for active microbial methanogenesis at the time of sampling. Overall, this method is a powerful tool for estimating species-resolved, single-cell rates of anaerobic metabolism in low-biomass environments while simultaneously linking genomes to phenomes at the single-cell level. We reveal active elemental cycling conducted by several species, with a large portion attributable to Ca. Desulforudis audaxviator.
Asunto(s)
Ecosistema , Ambiente , Transporte de Electrón , Sulfatos/química , Respiración de la CélulaRESUMEN
Written and oral communication are skills graduate students often request training in and supervisors often bemoan the lack of. We describe an approach to address this training gap using an instructional model that integrates experienced research-active PIs with an expert in the study and teaching of technical writing.
Asunto(s)
Comunicación , Escritura , HumanosRESUMEN
Single-celled microbial eukaryotes inhabit deep-sea hydrothermal vent environments and play critical ecological roles in the vent-associated microbial food web. 18S rRNA amplicon sequencing of diffuse venting fluids from four geographically- and geochemically-distinct hydrothermal vent fields was applied to investigate community diversity patterns among protistan assemblages. The four vent fields include Axial Seamount at the Juan de Fuca Ridge, Sea Cliff and Apollo at the Gorda Ridge, all in the NE Pacific Ocean, and Piccard and Von Damm at the Mid-Cayman Rise in the Caribbean Sea. We describe species diversity patterns with respect to hydrothermal vent field and sample type, identify putative vent endemic microbial eukaryotes, and test how vent fluid geochemistry may influence microbial community diversity. At a semi-global scale, microbial eukaryotic communities at deep-sea vents were composed of similar proportions of dinoflagellates, ciliates, Rhizaria, and stramenopiles. Individual vent fields supported distinct and highly diverse assemblages of protists that included potentially endemic or novel vent-associated strains. These findings represent a census of deep-sea hydrothermal vent protistan communities. Protistan diversity, which is shaped by the hydrothermal vent environment at a local scale, ultimately influences the vent-associated microbial food web and the broader deep-sea carbon cycle.
Asunto(s)
Respiraderos Hidrotermales , Microbiota , Agua de Mar , Filogenia , Eucariontes/genética , Microbiota/genéticaRESUMEN
OBJECTIVE: The objective of this study was to examine the feasibility and success rate of intraoperative injection of radiotracer and blue dye performed by the surgeon without the use of preoperative lymphoscintigraphy for the detection of sentinel lymph nodes in clinically early stage vulvar cancer. METHODS: All patients with clinically early stage vulvar cancer who underwent attempted sentinel lymph node biopsy using intraoperative injection of Technetium-99 m (99mTc) tracer and blue dye performed by the surgeon after induction of anesthesia at single academic institution from 12/2009 to 5/2022 were identified. Demographic and clinicopathologic variables were collected. Data were compared using descriptive statistics. RESULTS: One hundred sixty-four patients (median age 66.4 years) underwent intraoperative injection of radioactive tracer and dye for sentinel lymph node biopsy. Most patients (n = 156, 95.1%) were white. Squamous cell carcinoma accounted for 138 cases (84.1%), melanoma for 10 (6.1%), extra-mammary invasive Paget's disease for 11 (6.7%), and other histologies for 5 (3%). A majority of cases were stage I disease on final pathology (n = 119, 72.6%). Most patients (n = 117, 71%) had tumors located within 2 cm of the midline and underwent planned bilateral groin assessment, while 47 (29%) had well lateralized lesions and underwent unilateral groin assessment. For the patients undergoing unilateral groin assessment, 44 of 47 (93.6%) had successful unilateral mapping. Of the patients who underwent bilateral groin assessment, 87 of 117 (74.4%) had successful bilateral mapping, and 26 of 117 (22.2%) had successful unilateral mapping. Of the 26 patients who underwent bilateral assessment but only had unilateral mapping, 19 had unilateral mapping to ipsilateral groin but failed contralateral mapping, six had midline lesions with successful mapping to one groin but failed mapping to the other groin, and one had unilateral mapping to the contralateral groin but not ipsilateral groin. The total successful sentinel lymph node mapping rate in this cohort was 86.5% (243/281 total sentinel lymph node attempts). CONCLUSION: In this cohort, the overall success rate of sentinel lymph node mapping and biopsy was 86.5%. The high rate of successful sentinel lymph node mapping supports the use of intraoperative radiotracer and blue dye injection by trained providers.
Asunto(s)
Ganglio Linfático Centinela , Neoplasias de la Vulva , Femenino , Humanos , Anciano , Biopsia del Ganglio Linfático Centinela , Neoplasias de la Vulva/diagnóstico por imagen , Neoplasias de la Vulva/cirugía , Neoplasias de la Vulva/patología , Ganglios Linfáticos/patología , Trazadores Radiactivos , Estudios de Factibilidad , Metástasis Linfática/patología , Escisión del Ganglio Linfático , Ganglio Linfático Centinela/diagnóstico por imagen , Ganglio Linfático Centinela/cirugía , Ganglio Linfático Centinela/patologíaRESUMEN
Alkaline fluids venting from chimneys of the Lost City hydrothermal field flow from a potentially vast microbial habitat within the seafloor where energy and organic molecules are released by chemical reactions within rocks uplifted from Earth's mantle. In this study, we investigated hydrothermal fluids venting from Lost City chimneys as windows into subseafloor environments where the products of geochemical reactions, such as molecular hydrogen (H2), formate, and methane, may be the only available sources of energy for biological activity. Our deep sequencing of metagenomes and metatranscriptomes from these hydrothermal fluids revealed a few key species of archaea and bacteria that are likely to play critical roles in the subseafloor microbial ecosystem. We identified a population of Thermodesulfovibrionales (belonging to phylum Nitrospirota) as a prevalent sulfate-reducing bacterium that may be responsible for much of the consumption of H2 and sulfate in Lost City fluids. Metagenome-assembled genomes (MAGs) classified as Methanosarcinaceae and Candidatus Bipolaricaulota were also recovered from venting fluids and represent potential methanogenic and acetogenic members of the subseafloor ecosystem. These genomes share novel hydrogenases and formate dehydrogenase-like sequences that may be unique to hydrothermal environments where H2 and formate are much more abundant than carbon dioxide. The results of this study include multiple examples of metabolic strategies that appear to be advantageous in hydrothermal and subsurface alkaline environments where energy and carbon are provided by geochemical reactions. IMPORTANCE The Lost City hydrothermal field is an iconic example of a microbial ecosystem fueled by energy and carbon from Earth's mantle. Uplift of mantle rocks into the seafloor can trigger a process known as serpentinization that releases molecular hydrogen (H2) and creates unusual environmental conditions where simple organic carbon molecules are more stable than dissolved inorganic carbon. This study provides an initial glimpse into the kinds of microbes that live deep within the seafloor where serpentinization takes place, by sampling hydrothermal fluids exiting from the Lost City chimneys. The metabolic strategies that these microbes appear to be using are also shared by microbes that inhabit other sites of serpentinization, including continental subsurface environments and natural springs. Therefore, the results of this study contribute to a broader, interdisciplinary effort to understand the general principles and mechanisms by which serpentinization-associated processes can support life on Earth and perhaps other worlds.
Asunto(s)
Ecosistema , Respiraderos Hidrotermales , Archaea/genética , Archaea/metabolismo , Bacterias/genética , Bacterias/metabolismo , Formiatos/metabolismo , Hidrógeno/metabolismo , Respiraderos Hidrotermales/microbiología , Sulfatos/metabolismoRESUMEN
BACKGROUND: High-grade serous ovarian cancer (HGSOC) is the most common subtype of ovarian cancer and is associated with high mortality rates. Surgical outcome is one of the most important prognostic factors. There are no valid biomarkers to identify which patients may benefit from a primary debulking approach. OBJECTIVE: Our study aimed to discover and validate a predictive panel for surgical outcome of residual tumor mass after first-line debulking surgery. STUDY DESIGN: Firstly, "In silico" analysis of publicly available datasets identified 200 genes as predictors for surgical outcome. The top selected genes were then validated using the novel Nanostring method, which was applied for the first time for this particular research objective. 225 primary ovarian cancer patients with well annotated clinical data and a complete debulking rate of 60% were compiled for a clinical cohort. The 14 best rated genes were then validated through the cohort, using immunohistochemistry testing. Lastly, we used our biomarker expression data to predict the presence of miliary carcinomatosis patterns. RESULTS: The Nanostring analysis identified 37 genes differentially expressed between optimal and suboptimal debulked patients (p < 0.05). The immunohistochemistry validated the top 14 genes, reaching an AUC Ø0.650. The analysis for the prediction of miliary carcinomatosis patterns reached an AUC of Ø0.797. CONCLUSION: The tissue-based biomarkers in our analysis could not reliably predict post-operative residual tumor. Patient and non-patient-associated co-factors, surgical skills, and center experience remain the main determining factors when considering the surgical outcome at primary debulking in high-grade serous ovarian cancer patients.
Asunto(s)
Cistadenocarcinoma Seroso , Neoplasias Ováricas , Neoplasias Peritoneales , Bancos de Muestras Biológicas , Biomarcadores , Carcinoma Epitelial de Ovario , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/cirugía , Femenino , Humanos , Neoplasia Residual , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Estudios Prospectivos , Resultado del TratamientoRESUMEN
PURPOSE OF REVIEW: This review provides an update on recent developments in cell-based immunotherapy in gynecologic cancers. RECENT FINDINGS: Chimeric antigen receptor (CAR) technology has made significant progress allowing now for not only expressing CARs on T-cells, but also on other immune effector cells, such as natural killer cells and macrophages. Cell-based vaccines have started to show promising results in clinical trials. SUMMARY: Cell-based immunotherapies in gynecologic cancers continue to evolve with promising clinical efficacy in select patients.
Asunto(s)
Neoplasias de los Genitales Femeninos , Receptores Quiméricos de Antígenos , Femenino , Neoplasias de los Genitales Femeninos/terapia , Humanos , Inmunoterapia/métodos , Células Asesinas Naturales , Linfocitos TRESUMEN
Increasing inputs of organic matter (OM) are driving declining dissolved oxygen (DO) concentrations in coastal ecosystems worldwide. The quantity, source, and composition of OM transported to coastal ecosystems via stormwater runoff have been altered by land use changes associated with urbanization and subsequent hydrologic flows that accompany urban stormwater management. To elucidate the role of stormwater in the decline of coastal DO, rain event sampling of biochemical oxygen demand (BOD) in samples collected from the outfall of stormwater ponds and wetlands, as well as samples of largely untreated runoff carried by stormwater ditches, was conducted across a range of urban and suburban development densities. Sampling also included measurements of particulate and dissolved carbon and nitrogen, carbon and nitrogen stable isotopes, and chlorophyll-a. Results suggest stormwater may be a significant source of labile OM to receiving waters, especially during the first flush of runoff, even though BOD concentrations vary both among and within sites in response to rain events. BOD variability was best predicted by particulate OM (POM) and chlorophyll-a, rather than the larger pool of dissolved OM. These findings demonstrate the importance of managing episodic stormwater discharge, especially POM, from urbanized areas to mitigate DO impairment in larger downstream systems.
Asunto(s)
Movimientos del Agua , Contaminantes Químicos del Agua , Ecosistema , Monitoreo del Ambiente , Oxígeno , Lluvia , Contaminantes Químicos del Agua/análisisRESUMEN
The Lost City hydrothermal field on the Mid-Atlantic Ridge supports dense microbial life on the lofty calcium carbonate chimney structures. The vent field is fueled by chemical reactions between the ultramafic rock under the chimneys and ambient seawater. These serpentinization reactions provide reducing power (as hydrogen gas) and organic compounds that can serve as microbial food; the most abundant of these are methane and formate. Previous studies have characterized the interior of the chimneys as a single-species biofilm inhabited by the Lost City Methanosarcinales, but they also indicated that this methanogen is unable to metabolize formate. The new metagenomic results presented here indicate that carbon cycling in these Lost City chimney biofilms could depend on the metabolism of formate by Chloroflexi populations. Additionally, we present evidence for metabolically diverse, formate-utilizing Sulfurovum populations and new genomic and phylogenetic insights into the unique Lost City MethanosarcinalesIMPORTANCE Primitive forms of life may have originated around hydrothermal vents at the bottom of the ancient ocean. The Lost City hydrothermal vent field, fueled by just rock and water, provides an analog for not only primitive ecosystems but also potential extraterrestrial rock-powered ecosystems. The microscopic life covering the towering chimney structures at the Lost City has been previously documented, yet little is known about the carbon cycling in this ecosystem. These results provide a better understanding of how carbon from the deep subsurface can fuel rich microbial ecosystems on the seafloor.
Asunto(s)
Chloroflexi/genética , Formiatos/metabolismo , Genoma Bacteriano , Océano Atlántico , Carbono/metabolismo , Chloroflexi/metabolismo , Respiraderos Hidrotermales/microbiologíaRESUMEN
The Lost City hydrothermal field is a dramatic example of the biological potential of serpentinization. Microbial life is prevalent throughout the Lost City chimneys, powered by the hydrogen gas and organic molecules produced by serpentinization and its associated geochemical reactions. Microbial life in the serpentinite subsurface below the Lost City chimneys, however, is unlikely to be as dense or active. The marine serpentinite subsurface poses serious challenges for microbial activity, including low porosities, the combination of stressors of elevated temperature, high pH and a lack of bioavailable ∑CO2. A better understanding of the biological opportunities and challenges in serpentinizing systems would provide important insights into the total habitable volume of Earth's crust and for the potential of the origin and persistence of life in Earth's subsurface environments. Furthermore, the limitations to life in serpentinizing subsurface environments on Earth have significant implications for the habitability of subsurface environments on ocean worlds such as Europa and Enceladus. Here, we review the requirements and limitations of life in serpentinizing systems, informed by our research at the Lost City and the underwater mountain on which it resides, the Atlantis Massif. This article is part of a discussion meeting issue 'Serpentinite in the Earth System'.
Asunto(s)
Respiraderos Hidrotermales/química , Minerales/química , Océanos y Mares , Temperatura , Oligoelementos/químicaRESUMEN
Hyperthermophilic methanogens are often H2 limited in hot subseafloor environments, and their survival may be due in part to physiological adaptations to low H2 conditions and interspecies H2 transfer. The hyperthermophilic methanogen Methanocaldococcus jannaschii was grown in monoculture at high (80 to 83 µM) and low (15 to 27 µM) aqueous H2 concentrations and in coculture with the hyperthermophilic H2 producer Thermococcus paralvinellae The purpose was to measure changes in growth and CH4 production kinetics, CH4 fractionation, and gene expression in M. jannaschii with changes in H2 flux. Growth and cell-specific CH4 production rates of M. jannaschii decreased with decreasing H2 availability and decreased further in coculture. However, cell yield (cells produced per mole of CH4 produced) increased 6-fold when M. jannaschii was grown in coculture rather than monoculture. Relative to high H2 concentrations, isotopic fractionation of CO2 to CH4 (εCO2-CH4) was 16 larger for cultures grown at low H2 concentrations and 45 and 56 larger for M. jannaschii growth in coculture on maltose and formate, respectively. Gene expression analyses showed H2-dependent methylene-tetrahydromethanopterin (H4MPT) dehydrogenase expression decreased and coenzyme F420-dependent methylene-H4MPT dehydrogenase expression increased with decreasing H2 availability and in coculture growth. In coculture, gene expression decreased for membrane-bound ATP synthase and hydrogenase. The results suggest that H2 availability significantly affects the CH4 and biomass production and CH4 fractionation by hyperthermophilic methanogens in their native habitats.IMPORTANCE Hyperthermophilic methanogens and H2-producing heterotrophs are collocated in high-temperature subseafloor environments, such as petroleum reservoirs, mid-ocean ridge flanks, and hydrothermal vents. Abiotic flux of H2 can be very low in these environments, and there is a gap in our knowledge about the origin of CH4 in these habitats. In the hyperthermophile Methanocaldococcus jannaschii, growth yields increased as H2 flux, growth rates, and CH4 production rates decreased. The same trend was observed increasingly with interspecies H2 transfer between M. jannaschii and the hyperthermophilic H2 producer Thermococcus paralvinellae With decreasing H2 availability, isotopic fractionation of carbon during methanogenesis increased, resulting in isotopically more negative CH4 with a concomitant decrease in H2-dependent methylene-tetrahydromethanopterin dehydrogenase gene expression and increase in F420-dependent methylene-tetrahydromethanopterin dehydrogenase gene expression. The significance of our research is in understanding the nature of hyperthermophilic interspecies H2 transfer and identifying biogeochemical and molecular markers for assessing the physiological state of methanogens and possible source of CH4 in natural environments.
Asunto(s)
Isótopos de Carbono/metabolismo , Expresión Génica , Hidrógeno/metabolismo , Methanocaldococcus/fisiología , Thermococcus/fisiología , Hidrógeno/deficiencia , Metano/metabolismo , Methanocaldococcus/genética , Methanocaldococcus/crecimiento & desarrolloRESUMEN
Exposure to microbial pathogens is the primary concern of sanitary sewer overflows; however, sewage spills may also be a significant source of toxic metals, including methylmercury (MeHg). Between November 2015 and January 2017, after Hurricane Joaquin, surface water samples were collected routinely from three creeks in Columbia, SC. Routine sampling coincided with six sewage spills. Total mercury (THg) and MeHg (unfiltered and filtered) and 32 other metals (filtered) were measured. Compared with surface water samples, THg (unfiltered and filtered), MeHg (unfiltered), and 19 other metals were significantly higher in sewage spills (all log-transformed) (two-tailed test, < 0.05 for all, = 38-42). Toxic weighting factors were applied to 18 metals, including THg and MeHg, in samples collected directly from sewage spills ( = 3-4) and a wastewater outfall ( = 5). On average, sewage was 18.2 and 12.0 times more toxic for THg and MeHg, respectively, and 1.75 times more toxic for all 18 metals, compared to treated effluent from the wastewater outfall. Results suggest sewage spills were a source of inorganic Hg, MeHg, and other metals to the receiving waters and may potentially contribute to water quality impairments.
Asunto(s)
Monitoreo del Ambiente , Contaminantes Químicos del Agua/análisis , Metales/análisis , Compuestos de Metilmercurio/análisis , Aguas del Alcantarillado , South Carolina , Aguas Residuales/químicaRESUMEN
We investigated microbial life preserved in a hydrothermally inactive silicabarite chimney in comparison with an active barite chimney and sediment from the Loki's Castle low-temperature venting area at the Arctic Mid-Ocean Ridge (AMOR) using lipid biomarkers. Carbon and sulfur isotopes were used to constrain possible metabolic pathways. Multiple sulfur (dδ34S, Δ33S) isotopes on barite over a cross section of the extinct chimney range between 21.1 and 22.5 % in δ34S, and between 0.020 and 0.034 % in Δ33S, indicating direct precipitation from seawater. Biomarker distributions within two discrete zones of this silicabarite chimney indicate a considerable difference in abundance and diversity of microorganisms from the chimney exterior to the interior. Lipids in the active and inactive chimney barite and sediment were dominated by a range of 13C-depleted unsaturated and branched fatty acids with δ13C values between -39.7 and -26.7 %, indicating the presence of sulfur-oxidizing and sulfate-reducing bacteria. The majority of lipids (99.5 %) in the extinct chimney interior that experienced high temperatures were of archaeal origin. Unusual glycerol monoalkyl glycerol tetraethers (GMGT) with 04 rings were the dominant compounds suggesting the presence of mainly (hyper-) thermophilic archaea. Isoprenoid hydrocarbons with δ13C values as low as -46 % also indicated the presence of methanogens and possibly methanotrophs.
Asunto(s)
Sedimentos Geológicos/microbiología , Respiraderos Hidrotermales/microbiología , Microbiota , Archaea/química , Archaea/aislamiento & purificación , Regiones Árticas , Bacterias/química , Bacterias/aislamiento & purificación , Sulfato de Bario/análisis , Ácidos Grasos/análisis , Sedimentos Geológicos/química , Respiraderos Hidrotermales/química , Océanos y Mares , Radioisótopos/análisis , Dióxido de Silicio/análisisRESUMEN
â¢Deloyers procedure is an alternative to ileorectal anastomosis.â¢Deloyers procedure can be performed after a prior partial colectomy.â¢Use of this procedure may help achieve complete gross resection during cytoreductive surgery.
RESUMEN
Introduction: Advanced mixed epithelial endometrial carcinomas are rare high-grade cancers with a poor prognosis. A clear cell component infers relative chemotherapy insensitivity, likely further increased by p53 wild type status and MMR deficiency. PD-1 inhibition for MMR deficient endometrial cancers has been recently added to first-line adjuvant treatment in combination with platinum-based chemotherapy. Information on de-escalation of adjuvant treatment to PD-1 inhibition alone without chemotherapy is sparse. Case Presentation: Here, we present a patient with advanced stage mixed epithelial endometrial carcinoma, a clear cell component and MMR deficiency who underwent de-escalated adjuvant treatment with PD-1 inhibition alone without simultaneous chemotherapy. Conclusion: Histotype-agnostic adjuvant monotherapy with checkpoint immune inhibitors alone appears to be a highly effective even in the rare mixed endometrial carcinomas if MMR protein deficient as described in this case report.
RESUMEN
Deep-sea hydrothermal vent geochemistry shapes the foundation of the microbial food web by fueling chemolithoautotrophic microbial activity. Microbial eukaryotes (or protists) play a critical role in hydrothermal vent food webs as consumers and hosts of symbiotic bacteria, and as a nutritional source to higher trophic levels. We measured microbial eukaryotic cell abundance and predation pressure in low-temperature diffuse hydrothermal fluids at the Von Damm and Piccard vent fields along the Mid-Cayman Rise in the Western Caribbean Sea. We present findings from experiments performed under in situ pressure that show cell abundances and grazing rates higher than those done at 1 atmosphere (shipboard ambient pressure); this trend was attributed to the impact of depressurization on cell integrity. A relationship between the protistan grazing rate, prey cell abundance, and temperature of end-member hydrothermal vent fluid was observed at both vent fields, regardless of experimental approach. Our results show substantial protistan biomass at hydrothermally fueled microbial food webs, and when coupled with improved grazing estimates, suggest an important contribution of grazers to the local carbon export and supply of nutrient resources to the deep ocean.
Asunto(s)
Respiraderos Hidrotermales , Animales , Biomasa , Respiraderos Hidrotermales/microbiología , Conducta Predatoria , Filogenia , Bacterias/genéticaRESUMEN
The upper mantle is critical for our understanding of terrestrial magmatism, crust formation, and element cycling between Earth's solid interior, hydrosphere, atmosphere, and biosphere. Mantle composition and evolution have been primarily inferred by surface sampling and indirect methods. We recovered a long (1268-meter) section of serpentinized abyssal mantle peridotite interleaved with thin gabbroic intrusions. We find depleted compositions with notable variations in mantle mineralogy controlled by melt flow. Dunite zones have predominantly intermediate dips, in contrast to the originally steep mantle fabrics, indicative of oblique melt transport. Extensive hydrothermal fluid-rock interaction is recorded across the full depth of the core and is overprinted by oxidation in the upper 200 meters. Alteration patterns are consistent with vent fluid composition in the nearby Lost City hydrothermal field.
RESUMEN
OBJECTIVE: To analyze mortality trends in uterine cancer in the United States over 50 years with an emphasis on age and race and ethnicity. METHODS: Data on uterine cancer deaths from 1969 to 2018 were obtained from the National Center for Health Statistics. Trends were examined by age and race and ethnicity after adjustment for the hysterectomy rate and pregnancy. RESULTS: Uterine cancer mortality decreased between 1969 and 1997 (from 6.03 to 4.00/100,000) but increased between 1997 and 2018 (from 4.00 to 5.02/100,000). From 2001 to 2018, mortality rates increased by 1.25-fold across all age groups. In 2018, the mortality rate from uterine cancer for patients aged 70 years or older and 60-69 years was sixfold and threefold higher, respectively, than in younger patients (aged 50-59 years) (54.87/100,000 vs 27.80/100,000 vs 8.70/100,000). The mortality rate for non-Hispanic Black women was 2.2-fold higher than for non-Hispanic White, Hispanic, and non-Hispanic Asian or Pacific Islander women (17.6/100,000 vs 7.82/100,000, 6.54/100,000, and 4.24/100,000, respectively). On an intersection analysis of age and race, non-Hispanic Black women aged older than 60 years had a threefold higher mortality rate than non-Hispanic White women (72/100,000 vs 24/100,000). A notable finding was that young non-Hispanic Black and Hispanic women (30-39 years) had the highest annual increases in mortality at 3.3% and 3.8% per year compared with 2.2% in non-Hispanic White women. CONCLUSION: Since 2001, the uterine cancer mortality rate has increased across all four racial and ethnic groups examined, with the highest increase seen among non-Hispanic Black women. The largest increase in mortality was observed among younger non-Hispanic Black and Hispanic women.
Asunto(s)
Neoplasias Uterinas , Femenino , Humanos , Embarazo , Etnicidad , Hispánicos o Latinos , Histerectomía , Estados Unidos/epidemiología , Neoplasias Uterinas/mortalidad , Negro o AfroamericanoRESUMEN
The stable isotopes of organic matter can provide valuable information on carbon cycling dynamics, microbial metabolisms, and past climates. Since bulk measurements may mask dynamic changes to critical portions of the organic pool, researchers are increasingly isolating individual compounds for isotopic analysis. The amount of carbon isolated is frequently small, requiring specialized equipment for its analysis. We present a simple and accurate method to measure the δ(13)C values of µg-amounts of organic compounds and dissolved organic matter in freshwaters using wet oxidation and a GasBench II preparation device. Samples containing 3 µg C can be analyzed with a precision of <0.4. For samples containing 1.2 µg C, the precision is <0.8. The blank is estimated to be ~0.2 µg C. The accuracy of the method is demonstrated for a wide range of compounds including those that are difficult to oxidize such as humic acid and phthalic acid. The δ(13)C values of DOC from river and riparian ground water determined by this method are comparable with those determined with an elemental analyzer on freeze-dried samples of DOC. The low detection limit and the ease with which it can be combined with isolation techniques such as liquid chromatography make this technique attractive for the off-line analysis of organic compounds, and open new possibilities for the development of methodologies for compound-specific carbon isotope analysis of complex mixtures separated by HPLC.
Asunto(s)
Isótopos de Carbono/análisis , Espectrometría de Masas/métodos , Compuestos Orgánicos/química , Colesterol/química , Cromatografía Líquida de Alta Presión , Agua Dulce/química , Ácido Gálico/análogos & derivados , Ácido Gálico/química , Glucosa/química , Sustancias Húmicas/análisis , Límite de Detección , Espectrometría de Masas/instrumentación , Oxidación-Reducción , Ácidos Ftálicos/química , Acetato de Potasio/química , Reproducibilidad de los ResultadosRESUMEN
Deptor is an mTOR binding protein that affects cell metabolism. We hypothesized that knockdown (KD) of Deptor in C2C12 myocytes will increase protein synthesis via stimulating mTOR-S6K1 signaling. Deptor KD was achieved using lentiviral particles containing short hairpin (sh)RNA targeting the mouse Deptor mRNA sequence, and control cells were transfected with a scrambled control shRNA. KD reduced Deptor mRNA and protein content by 90%, which increased phosphorylation of mTOR kinase substrates, 4E-BP1 and S6K1, and concomitantly increased protein synthesis. Deptor KD myoblasts were both larger in diameter and exhibited an increased mean cell volume. Deptor KD increased the percentage of cells in the S phase, coincident with an increased phosphorylation (S807/S811) of retinoblastoma protein (pRb) that is critical for the G(1) to S phase transition. Deptor KD did not appear to alter basal apoptosis or autophagy, as evidenced by the lack of change for cleaved caspase-3 and light chain (LC)3B, respectively. Deptor KD increased proliferation rate and enhanced myotube formation. Finally, in vivo Deptor KD (~50% reduction) by electroporation into gastrocnemius of C57/BL6 mice did not alter weight or protein synthesis in control muscle. However, Deptor KD prevented atrophy produced by 3 d of hindlimb immobilization, at least in part by increasing protein synthesis. Thus, our data support the hypothesis that Deptor is an important regulator of protein metabolism in myocytes and demonstrate that decreasing Deptor expression in vivo is sufficient to ameliorate muscle atrophy.