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1.
Nature ; 600(7890): 670-674, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34937895

RESUMO

Carbon capture and storage (CCS) is a key technology to mitigate the environmental impact of carbon dioxide (CO2) emissions. An understanding of the potential trapping and storage mechanisms is required to provide confidence in safe and secure CO2 geological sequestration1,2. Depleted hydrocarbon reservoirs have substantial CO2 storage potential1,3, and numerous hydrocarbon reservoirs have undergone CO2 injection as a means of enhanced oil recovery (CO2-EOR), providing an opportunity to evaluate the (bio)geochemical behaviour of injected carbon. Here we present noble gas, stable isotope, clumped isotope and gene-sequencing analyses from a CO2-EOR project in the Olla Field (Louisiana, USA). We show that microbial methanogenesis converted as much as 13-19% of the injected CO2 to methane (CH4) and up to an additional 74% of CO2 was dissolved in the groundwater. We calculate an in situ microbial methanogenesis rate from within a natural system of 73-109 millimoles of CH4 per cubic metre (standard temperature and pressure) per year for the Olla Field. Similar geochemical trends in both injected and natural CO2 fields suggest that microbial methanogenesis may be an important subsurface sink of CO2 globally. For CO2 sequestration sites within the environmental window for microbial methanogenesis, conversion to CH4 should be considered in site selection.


Assuntos
Dióxido de Carbono , Água Subterrânea , Metano , Bactérias/metabolismo , Dióxido de Carbono/análise , Geologia , Metano/metabolismo , Temperatura
2.
Proc Natl Acad Sci U S A ; 119(9)2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35193971

RESUMO

Women continue to be underrepresented in leadership positions. This underrepresentation is at least partly driven by gender stereotypes that associate men, but not women, with achievement-oriented, agentic traits (e.g., assertive and decisive). These stereotypes are expressed and perpetuated in language, with women being described in less agentic terms than men. The present research suggests that appointing women to the top tiers of management can mitigate these deep-rooted stereotypes that are expressed in language. We use natural language processing techniques to analyze over 43,000 documents containing 1.23 billion words, finding that hiring female chief executive officers and board members is associated with changes in organizations' use of language, such that the semantic meaning of being a woman becomes more similar to the semantic meaning of agency. In other words, hiring women into leadership positions helps to associate women with characteristics that are critical for leadership success. Importantly, our findings suggest that changing organizational language through increasing female representation might provide a path for women to break out of the double bind: when female leaders are appointed into positions of power, women are more strongly associated with the positive aspects of agency (e.g., independent and confident) in language but not at the cost of a reduced association with communality (e.g., kind and caring). Taken together, our findings suggest that female representation is not merely an end, but also a means to systemically change insidious gender stereotypes and overcome the trade-off between women being perceived as either competent or likeable.


Assuntos
Liderança , Cultura Organizacional , Seleção de Pessoal , Fatores Sexuais , Estereotipagem , Feminino , Humanos
3.
Environ Sci Technol ; 57(26): 9459-9473, 2023 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-37327355

RESUMO

Carbon capture and storage (CCS) is an important component in many national net-zero strategies. Ensuring that CO2 can be safely and economically stored in geological systems is critical. To date, CCS research has focused on the physiochemical behavior of CO2, yet there has been little consideration of the subsurface microbial impact on CO2 storage. However, recent discoveries have shown that microbial processes (e.g., methanogenesis) can be significant. Importantly, methanogenesis may modify the fluid composition and the fluid dynamics within the storage reservoir. Such changes may subsequently reduce the volume of CO2 that can be stored and change the mobility and future trapping systematics of the evolved supercritical fluid. Here, we review the current knowledge of how microbial methanogenesis could impact CO2 storage, including the potential scale of methanogenesis and the range of geologic settings under which this process operates. We find that methanogenesis is possible in all storage target types; however, the kinetics and energetics of methanogenesis will likely be limited by H2 generation. We expect that the bioavailability of H2 (and thus potential of microbial methanogenesis) will be greatest in depleted hydrocarbon fields and least within saline aquifers. We propose that additional integrated monitoring requirements are needed for CO2 storage to trace any biogeochemical processes including baseline, temporal, and spatial studies. Finally, we suggest areas where further research should be targeted in order to fully understand microbial methanogenesis in CO2 storage sites and its potential impact.


Assuntos
Dióxido de Carbono , Água Subterrânea , Carbono
4.
Ann Hum Biol ; 47(6): 564-571, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32945183

RESUMO

BACKGROUND: Clinicians and researchers use a variety of intrauterine growth curves to classify NICU infants as small (SGA), appropriate (AGA), or large for gestational age (LGA). Since curve creation methods and samples vary, SGA/AGA/LGA cut-offs and resulting subgroups of infants vary among curves and impact outcome study findings - limiting generalisability. AIM: Determine how two international and two US-specific curves classified US NICU infants. SUBJECTS AND METHODS: Classified 192,888 infants from US NICUs (2013-2016) as SGA or LGA for birthweight, length, and head circumference, using the international Fenton and INTERGROWTH-21st curves and US-specific Olsen and Lubchenco (historical) curves. RESULTS: Modern curves classified approximately 10% of infants as SGA up to 32 weeks, but older infants had increased variability. The INTERGROWTH-21st curves consistently had rates above 10% for LGA after 32 weeks. CONCLUSIONS: While Olsen and Fenton both fit, the Olsen curves had overall best-fit for our sample of US NICU infants. The INTERGROWTH-21st curves fit the definitions for SGA and LGA for younger ages, but inferences outside of these definitions are unwarranted due to limited sample size. The INTERGROWTH-21st sample used for 33 weeks and older infants was physically smaller at the upper percentiles than our sample of US infants.


Assuntos
Estatura , Peso Corporal , Cabeça/anatomia & histologia , Recém-Nascido/crescimento & desenvolvimento , Idade Gestacional , Gráficos de Crescimento , Humanos , Unidades de Terapia Intensiva Neonatal , Estados Unidos
5.
Hum Reprod ; 31(7): 1522-30, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27165618

RESUMO

STUDY QUESTION: What are the direct effects and physiological role of anti-Müllerian hormone (AMH) during primate follicular development and function at specific stages of folliculogenesis? SUMMARY ANSWER: AMH actions in the primate ovary may be stage-dependent, directly promoting pre-antral follicle growth while inhibiting antral follicle maturation and dominant follicle selection. WHAT IS KNOWN ALREADY: AMH is expressed in the adult ovary, particularly in developing follicles. Studies in mice suggest that AMH suppresses pre-antral follicle growth in vitro, and inhibits primordial follicle recruitment and FSH-stimulated antral follicle steroidogenesis. STUDY DESIGN, SIZE, DURATION: For in vitro study, secondary follicles were isolated from ovaries of 12 rhesus macaques and cultured for 5 weeks. For in vivo study, intraovarian infusion was conducted on five monkeys for the entire follicular phase during two spontaneous menstrual cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS: For in vitro study, individual follicles were cultured in a 5% O2 environment, in alpha minimum essential medium supplemented with recombinant human FSH. Follicles were randomly assigned to treatments of recombinant human AMH protein or neutralizing anti-human AMH antibody (AMH-Ab). Follicle survival, growth, steroid production, steroidogenic enzyme expression, and oocyte maturation were assessed. For in vivo study, ovaries were infused with control vehicle or AMH-Ab during the follicular phase of the menstrual cycle. Cycle length, serum steroid levels, and antral follicle growth were evaluated. MAIN RESULTS AND THE ROLE OF CHANCE: AMH exposure during culture weeks 0-3 (pre-antral stage) promoted, while AMH-Ab delayed, antrum formation of growing follicles compared with controls. AMH treatment during culture weeks 3-5 (antral stage) decreased (P < 0.05) estradiol (E2) production, as well as the mRNA expression of cytochrome P450 family 19 subfamily A polypeptide 1, by antral follicles relative to controls, whereas AMH-Ab increased (P < 0.05) follicular mRNA levels of the enzyme. Intraovarian infusion of AMH-Ab during the follicular phase of the menstrual cycle increased (P < 0.05) the average levels of serum E2 compared with those of the control cycles. Three of the five AMH-Ab-treated ovaries displayed multiple (n = 2-9) medium-to-large (2-8 mm) antral follicles at the mid-cycle E2 peak, whereas only one large (4-7 mm) antral follicle was observed in all monkeys during their control cycles. The average levels of serum progesterone were higher (P < 0.05) during the luteal phase of cycles following the AMH-Ab infusion relative to the vehicle infusion. LIMITATIONS, REASONS FOR CAUTION: The in vitro study of AMH actions on cultured individual macaque follicles was limited to the interval from the secondary to small antral stage. A sequential study design was used for in vivo experiments, which may limit the power of the study. WIDER IMPLICATIONS OF THE FINDINGS: The current study provides novel information on direct actions and role of AMH during primate follicular development, and selection of a dominant follicle by the late follicular phase of the menstrual cycle. We hypothesize that AMH acts positively on follicular growth during the pre-antral stage in primates, but negatively impacts antral follicle maturation, which is different from what is reported in the mouse model. STUDY FUNDING/COMPETING INTERESTS: NIH NICHD R01HD082208, NIH ORWH/NICHD K12HD043488 (BIRCWH), NIH OD P51OD011092 (ONPRC), Collins Medical Trust. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable.


Assuntos
Hormônio Antimülleriano/farmacologia , Folículo Ovariano/efeitos dos fármacos , Animais , Hormônio Antimülleriano/sangue , Hormônio Antimülleriano/imunologia , Anticorpos Neutralizantes/farmacologia , Família 19 do Citocromo P450/metabolismo , Estradiol/biossíntese , Feminino , Macaca mulatta , Folículo Ovariano/crescimento & desenvolvimento , Progesterona/sangue , RNA Mensageiro/metabolismo , Distribuição Aleatória , Técnicas de Cultura de Tecidos
6.
Phys Rev Lett ; 116(10): 107202, 2016 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-27015507

RESUMO

We present evidence for nuclear spin-lattice relaxation driven by glassy nematic fluctuations in isovalent P-doped BaFe_{2}As_{2} single crystals. Both the ^{75}As and ^{31}P sites exhibit a stretched-exponential relaxation similar to the electron-doped systems. By comparing the hyperfine fields and the relaxation rates at these sites we find that the As relaxation cannot be explained solely in terms of magnetic spin fluctuations. We demonstrate that nematic fluctuations couple to the As nuclear quadrupolar moment and can explain the excess relaxation. These results suggest that glassy nematic dynamics are a common phenomenon in the iron-based superconductors.

7.
J Pediatr Gastroenterol Nutr ; 58(4): 409-16, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24231639

RESUMO

OBJECTIVE: The aim of the study was to evaluate the relation between nutritional intake (kilocalories, protein) and weight and length growth in preterm infants, and to describe their metabolic tolerance with a focus on those with high protein intake (≥ 4.6 g · kg(-1) · day(-1)). METHODS: Secondary analysis of data from appropriate-for-gestational age preterm infants in a 28-day randomized clinical trial that evaluated growth, tolerance, and safety of a new ultraconcentrated liquid human milk fortifier (original study n = 150). This subset of 56 infants had complete growth and nutrition data and met criteria for the original study's "efficacy analysis" (eg, >80% of kilocalorie intake from study diet). Nutritional intake was estimated, not actual. Regressions were used to test cumulative kilocalories and protein as the predictors of 28-day change in weight and length z scores (growth status), and to evaluate protein tolerance. RESULTS: Average intake was 118 ± 8 kcal · kg(-1) · day(-1) and 4.3 ± 0.4 g protein · kg(-1) · day(-1), with 16 ± 3 g · kg(-1) · day(-1) and 1.1 ± 0.2 cm/week growth for 28 days. Cumulative total kilocalories and protein were significant predictors of improved length z score (P = 0.0054, 0.0005) but not weight z score change. Regression models indicated that protein not kilocalories explained the improvement in length z score, with protein explaining 19% of the variability. The high protein group averaged 4.6 to 5.5 g · kg(-1) · day(-1) (n = 16). Protein tolerance was adequate for all of the study infants based on metabolic measures (blood urea nitrogen, serum carbon dioxide, pH). CONCLUSIONS: Higher cumulative protein intake was tolerated and overall lessened the commonly occurring decline in the length but not weight growth status in a 28-day study of preterm infants.


Assuntos
Proteínas Alimentares/administração & dosagem , Ingestão de Energia , Alimentos Fortificados , Recém-Nascido Prematuro/crescimento & desenvolvimento , Equilíbrio Ácido-Base , Nitrogênio da Ureia Sanguínea , Estatura , Peso Corporal , Dióxido de Carbono/sangue , Proteínas Alimentares/efeitos adversos , Suplementos Nutricionais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Leite Humano
8.
Nat Commun ; 15(1): 5655, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969674

RESUMO

Economic segregation is the geographical separation of people with different economic means. In this paper, we employ an archival study of attitudes in regions with varying degrees of economic segregation and a series of experimental studies measuring reactions to hypothetical levels of segregation to examine how segregation affects concerns about inequality. Combining correlational and experimental methods and examining attitudes about economic inequality in both the United States and South Africa, we show that when individuals of different means are segregated from each other, people are less likely to engage in economic comparisons and are therefore less concerned by inequality. Moreover, we find that this is true even when people are exposed to (and are aware of) the same levels of inequality, suggesting that segregation in and of itself affects attitudes about inequality. Our findings highlight the importance of economic segregation in shaping public attitudes about organizational and societal economic inequality.

9.
Ultramicroscopy ; 257: 113903, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38101083

RESUMO

Tri-beam microscopes comprising a fs-laser beam, a Xe+ plasma focused ion beam (PFIB) and an electron beam all in one chamber open up exciting opportunities for site-specific correlative microscopy. They offer the possibility of rapid ablation and material removal by fs-laser, subsequent polishing by Xe-PFIB milling and electron imaging of the same area. While tri-beam systems are capable of probing large (mm) volumes providing high resolution microscopical characterisation of 2D and 3D images across exceptionally wide range of materials and biomaterials applications, presenting high quality/low damage surfaces to the electron beam can present a significant challenge, especially given the large parameter space for optimisation. Here the optimal conditions and artefacts associated with large scale volume milling, mini test piece manufacture, serial sectioning and surface polishing are investigated, both in terms of surface roughness and surface quality for metallic, ceramic, mixed complex phase, carbonaceous, and biological materials. This provides a good starting place for those wishing to examine large areas or volumes by tri-beam microscopy across a range of materials.

10.
J Mol Cell Cardiol ; 62: 99-107, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23688780

RESUMO

Cardiac hypertrophy has been well-characterized at the level of transcription. During cardiac hypertrophy, genes normally expressed primarily during fetal heart development are re-expressed, and this fetal gene program is believed to be a critical component of the hypertrophic process. Recently, alternative splicing of mRNA transcripts has been shown to be temporally regulated during heart development, leading us to consider whether fetal patterns of splicing also reappear during hypertrophy. We hypothesized that patterns of alternative splicing occurring during heart development are recapitulated during cardiac hypertrophy. Here we present a study of isoform expression during pressure-overload cardiac hypertrophy induced by 10 days of transverse aortic constriction (TAC) in rats and in developing fetal rat hearts compared to sham-operated adult rat hearts, using high-throughput sequencing of poly(A) tail mRNA. We find a striking degree of overlap between the isoforms expressed differentially in fetal and pressure-overloaded hearts compared to control: forty-four percent of the isoforms with significantly altered expression in TAC hearts are also expressed at significantly different levels in fetal hearts compared to control (P<0.001). The isoforms that are shared between hypertrophy and fetal heart development are significantly enriched for genes involved in cytoskeletal organization, RNA processing, developmental processes, and metabolic enzymes. Our data strongly support the concept that mRNA splicing patterns normally associated with heart development recur as part of the hypertrophic response to pressure overload. These findings suggest that cardiac hypertrophy shares post-transcriptional as well as transcriptional regulatory mechanisms with fetal heart development.


Assuntos
Cardiomegalia/genética , Feto/metabolismo , Coração/embriologia , Miocárdio/metabolismo , Splicing de RNA/genética , RNA Mensageiro/genética , Processamento Alternativo/genética , Animais , Feminino , Técnicas In Vitro , Masculino , Miocárdio/patologia , Reação em Cadeia da Polimerase , Gravidez , Ratos , Ratos Sprague-Dawley , Análise de Sequência de RNA
11.
Br J Cancer ; 108(6): 1340-7, 2013 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-23412101

RESUMO

BACKGROUND: Mesothelioma is an incurable cancer originating from the mesothelial cells that line the pleural, peritoneal and pericardial cavities. These cells synthesise large quantities of surface glycoproteins, rendering them dependent upon efficient endoplasmic reticulum (ER) function. When faced with elevated levels of secretory protein load, cells are said to experience ER stress, which has been implicated in the pathogenesis of many human diseases including cancer. METHOD: We set out to measure markers of ER stress in malignant mesothelioma and to determine whether ER stress signalling correlates with clinical parameters. RESULTS: We observed that expression of the ER stress-responsive transcription factor C/EBP homologous protein (CHOP) correlated with patient survival and remained an independent prognostic variable in pairwise comparisons with all clinical variables tested. The most parsimonious multivariate model in our study comprised only performance status and CHOP staining. In contrast, expression of the ER stress-responsive phosphatase growth arrest and DNA damage 34 (GADD34) correlated with the degree of mesothelial differentiation, being lost progressively in biphasic and sarcomatoid mesotheliomas. CONCLUSION: Our findings suggest that staining for CHOP provides prognostic information that may be useful in the stratification of patients with mesothelioma. Staining for GADD34 may prove useful in classification of mesothelioma histopathology.


Assuntos
Biomarcadores Tumorais/metabolismo , Estresse do Retículo Endoplasmático , Proteínas de Choque Térmico/metabolismo , Mesotelioma/mortalidade , Proteína Fosfatase 1/metabolismo , Fator de Transcrição CHOP/metabolismo , Diferenciação Celular , Chaperona BiP do Retículo Endoplasmático , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Masculino , Mesotelioma/metabolismo , Mesotelioma/patologia , Estadiamento de Neoplasias , Prognóstico , Transdução de Sinais , Taxa de Sobrevida , Análise Serial de Tecidos
12.
Hum Reprod ; 28(5): 1267-79, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23427232

RESUMO

STUDY QUESTION: What are the appropriate conditions to vitrify the macaque ovarian cortex in a large-volume, closed system that will preserve functional pre-antral follicles? SUMMARY ANSWER: The combination of glycerol, ethylene glycol (EG) and polymers with cooling in liquid nitrogen (LN2) vapor and a two-step warming procedure was able to preserve tissue and follicle morphology as well as function of a small population of secondary follicles in the macaque ovarian cortex following vitrification in a closed system. WHAT IS KNOWN ALREADY: For prepubertal cancer patients or those who require immediate cancer therapy, ovarian tissue cryopreservation offers the only hope for future fertility. However, the efficacy of live birth from the transplantation of cryopreserved ovarian tissue is still unclear. In addition, live birth from cryopreserved ovarian tissue has only been demonstrated after tissue autotransplantation, which poses the risk of transmitting metastatic cancer cells back to the cancer survivor in certain cancers. STUDY DESIGN, SIZE, DURATION: Non-human primate model, n = 4, randomized, control versus treatment. End-points were collected from tissue histology, tissue culture (48 h) and isolated secondary follicle culture (6 weeks). PARTICIPANTS/MATERIALS, SETTING, METHODS: Two vitrification solutions (VSs) containing EG + glycerol (VEG) and EG + dimethylsulfoxide (VED) were examined for vitrification, devitrification and thermodynamic properties. Once the optimal VS was determined, macaque ovarian cortical pieces (3 × 3 × 0.5 mm(3)) were divided into fresh and two vitrified groups (VEG and VED). For the vitrification groups, tissues were exposed to 1/4, 1/2 and 1× VS for 5 min/step as well as 1× VS + polymers for 1 min at 37°C, loaded into high-security straws with 1 ml of VS + polymers, heat sealed and cooled in LN2 vapor. Samples were warmed in a 40°C water bath and cryoprotective agents were diluted with 1, 0.5, 0.25 and 0 M sucrose. Tissues were fixed for histological analysis and cultured with bromodeoxyuridine (BrdU). Secondary follicles from VEG tissues were encapsulated and cultured (n = 24/treatment/animal). Follicle health, diameter and steroid [progesterone, androstenedione (A4), estradiol (E2)] production were analyzed weekly. MAIN RESULTS AND THE ROLE OF CHANCE: Dense stroma and intact pre-antral follicles were observed using VS containing 27% glycerol, 27% EG and 0.8% polymers with cooling in LN2 vapor and a two-step warming. Higher cooling and warming rates led to fracturing. BrdU uptake was evident in granulosa cells of growing follicles in fresh and vitrified tissues. Secondary follicles from fresh tissues (70 ± 12%) and tissues vitrified with VEG (52 ± 2%) showed similar survival rates (all data: mean ± SEM; P > 0.05). For both groups, the initial follicle diameter was similar and increased (P < 0.05) by Week 3, but diameters in vitrified follicles were smaller (P < 0.05) by Week 6 (566 ± 27 µm) than those of the fresh follicles (757 ± 26 µm). Antrum formation rates were lower (P < 0.05) for vitrified (37 ± 6%) relative to fresh (64 ± 8%) follicles. There was no significant change in levels in culture media of E2, P4 and A4 between fresh and VEG groups at any time point during culture. LIMITATIONS, REASONS FOR CAUTION: Only in vitro studies are reported. Future in vivo tissue transplantation studies will be needed to confirm long-term function and fertility potential of vitrified ovarian tissues. WIDER IMPLICATIONS OF THE FINDINGS: This is the first demonstration of antral follicle development during 3D culture following ovarian tissue vitrification in a closed system using primate ovarian tissue. While diminished antrum formation and slower growth in vitro reflect residual cryodamage, continued development of ovarian tissue vitrification based on cryobiology principles using a non-human primate model will identify safe, practical and efficient protocols for eventual clinical use. Tissue function following heterotopic transplantation is currently being examined. STUDY FUNDING/COMPETING INTEREST(S): National Institutes of Health (NIH) Oncofertility Consortium UL1 RR024926 (1RL1-HD058293, HD058295, PL1 EB008542), the Eunice Kennedy Shriver NICHD/NIH (U54 HD018185) and ONPRC 8P51OD011092-53. G.M.F. works for the company that makes the polymers used in the current study.


Assuntos
Criopreservação , Oócitos/citologia , Folículo Ovariano/patologia , Técnicas de Cultura de Tecidos , Vitrificação , Animais , Crioprotetores/farmacologia , Etilenoglicol/química , Feminino , Glicerol/química , Macaca , Folículo Ovariano/efeitos dos fármacos , Ovário/patologia , Polímeros/química , Distribuição Aleatória , Técnicas de Reprodução Assistida , Manejo de Espécimes/métodos , Temperatura
13.
Hum Reprod ; 28(8): 2187-200, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23608357

RESUMO

STUDY QUESTION: Does fibrin introduced into the extracellular matrix affect the growth and maturation of individual primate follicles during encapsulated three-dimensional (3D) culture? SUMMARY ANSWER: While not altering follicle survival, fibrin-alginate (FIBRIN) improves macaque primary, but not secondary, follicle development during encapsulated 3D culture in terms of growth, steroidogenesis, anti-Müllerian hormone (AMH)/vascular endothelial growth factor (VEGF) production and oocyte maturation. WHAT IS KNOWN ALREADY: Efforts to grow non-human primate ovarian follicles from the secondary to the antral stage during encapsulated 3D culture have been successful. However, the growth and maturation of primary follicles in vitro has not been reported in primates, especially in chemically defined conditions. STUDY DESIGN, SIZE, DURATION: In vitro follicle maturation was investigated using the rhesus macaque (Macaca mulatta). Ovaries (n = 7 pairs) were obtained during the early follicular phase of the menstrual cycle (cycle day 1-4). Primary (80-120 µm diameter) and secondary (125-225 µm diameter) follicles were isolated mechanically, randomly assigned to experimental groups, encapsulated into alginate (0.25% w/v) or FIBRIN (25 mg/ml fibrinogen-0.25% alginate) and cultured for 13 and 5 weeks, respectively. MATERIALS, SETTING, METHODS: Individual follicles were cultured in alpha minimum essential medium supplemented with FSH. Follicle survival and growth were assessed by microscopy. Follicles that reached the antral stage were treated with recombinant hCG. Metaphase II (MII) oocytes were inseminated via ICSI. Follicle morphology was evaluated by hematoxylin and eosin (H&E) staining. Immunohistochemistry was performed for cytochrome P450 family 17 subfamily A polypeptide 1 (CYP17A1) and 19 subfamily A polypeptide 1 (CYP19A1). Culture medium was analyzed for estradiol (E2) and progesterone by chemiluminescence, androstenedione (A4) by radioimmunoassay, as well as anti-Müllerian hormone (AMH) and vascular endothelial growth factor (VEGF) by enzyme-linked immunosorbent assay. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 105 primary and 133 secondary follicles were collected. The presence of fibrin in the alginate matrix had no effect on either primary or secondary follicle survival. Growing primary and secondary follicles formed an antrum at Weeks 9 and 3, respectively. The percentage of growing follicles was higher (P < 0.05) for primary follicles cultured in FIBRIN than alginate at Week 13. The diameters were larger for the growing secondary follicles cultured in alginate than FIBRIN at Week 5 (P < 0.05). H&E staining revealed the typical morphology for small antral follicles. CPY17A1 immunostaining was detected in theca cells, while CYP19A1 was observed in granulosa cells. E2 increased (P < 0.05) during antrum formation in growing follicles at Week 9 for primary and Week 3 for secondary follicles. AMH levels in medium from growing primary follicles increased (P < 0.05) after Week 4 with peak levels at Weeks 9-11. AMH increased (P < 0.05) in growing secondary follicles at Weeks 3-5. VEGF levels in medium were elevated (P < 0.05) in growing primary follicles at Week 9. VEGF increased (P < 0.05) in medium from growing secondary follicles at Weeks 3-5. E2, AMH and VEGF production was higher (P < 0.05) in primary follicle culture with FIBRIN than alginate alone. One primary follicle cultured in FIBRIN (1 of 5 follicles harvested) and a secondary follicle cultured in alginate alone (1 of 15 follicles harvested) yielded an MII oocyte. The fertilized oocyte from primary follicle culture arrested without cell division after fertilization, while the oocyte from secondary follicle culture cleaved and reached the morula stage. LIMITATIONS, REASONS FOR CAUTION: The study reports on in vitro development and function of individual macaque follicles, that is limited to the interval from the primary and secondary stage to the small antral stage. The findings await translation to human ovarian follicles. WIDER IMPLICATIONS OF THE FINDINGS: The 3D model for primate follicle development offers a unique opportunity to investigate the growth and regulation of primate primary, as well as secondary follicles, and their enclosed oocytes, as they grow to the antral stage by monitoring and manipulating factors or signaling pathways in vitro. Since primate primary follicles, in addition to secondary follicles, can be cultured to the antral stage to provide mature oocytes, they represent an additional source of pre-antral follicles for in vitro follicle maturation with the potential to provide gametes for assisted reproductive technology as an option for fertility preservation in women, including patients with cancer. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by The Oncofertility Consortium (NIH U54 RR024347-HD058294, PL1-EB008542), NIH U54-HD18185 (Eunice Kennedy Shriver Specialized Cooperative Centers Program in Reproduction and Infertility Research), NIH ORWH/NICHD 2K12HD043488 (BIRCWH), Oregon National Primate Research Center 8P51OD011092. There are no conflicts of interest.


Assuntos
Fibrina/farmacologia , Macaca/fisiologia , Folículo Ovariano/efeitos dos fármacos , Animais , Hormônio Antimülleriano/metabolismo , Técnicas de Cultura de Células/veterinária , Gonadotropina Coriônica/farmacologia , Feminino , Fertilização , Hormônios Esteroides Gonadais/metabolismo , Técnicas de Maturação in Vitro de Oócitos/métodos , Técnicas de Maturação in Vitro de Oócitos/veterinária , Folículo Ovariano/crescimento & desenvolvimento , Folículo Ovariano/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
14.
Phys Rev Lett ; 111(20): 207201, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-24289706

RESUMO

We present 75As nuclear magnetic resonance data from measurements of a series of Ba(Fe(1-x)Co(x))2As2 crystals with 0.00≤x≤0.075 that reveals the coexistence of frozen antiferromagnetic domains and superconductivity for 0.060≤x≤0.071. Although bulk probes reveal no long range antiferromagnetic order beyond x=0.06, we find that the local spin dynamics reveal no qualitative change across this transition. The characteristic domain sizes vary by more than an order of magnitude, reaching a maximum variation at x=0.06. This inhomogeneous glassy dynamics may be an intrinsic response to the competition between superconductivity and antiferromagnetism in this system.

15.
J Exp Psychol Gen ; 152(3): 611-631, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36892902

RESUMO

Fake news can foster political polarization, foment division between groups, and encourage malicious behavior. Misinformation has cast doubt on the integrity of democratic elections, downplayed the seriousness of COVID-19, and increased vaccine hesitancy. Given the leading role that online groups play in the dissemination of fake news, in this research we examined how group-level factors contribute to sharing misinformation. By unobtrusively tracking interactions among 51,537 Twitter user dyads longitudinally over two time periods (n = 103,074), we found that group members who did not conform to the behavior of other group members by sharing fake news were subjected to reduced social interaction over time. We augmented this unique, ecologically valid behavioral data with another digital field study (N = 178,411) and five experiments to disentangle some of the causal mechanisms driving the observed effects. We found that social costs were higher for not sharing fake news versus other content, that specific types of deviant group members faced the greatest social costs, and that social costs explained fake news sharing above and beyond partisan identity and subjective accuracy assessments. Overall, our work illuminates the role of conformity pressure as a critical antecedent of the spread of misinformation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
COVID-19 , Mídias Sociais , Humanos , Desinformação , Emoções , Comportamento Social
16.
Clin Nutr ESPEN ; 58: 270-276, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38057017

RESUMO

BACKGROUND & AIMS: Short bowel syndrome (SBS) is the leading cause of chronic intestinal failure. The duration of parenteral support (PS) and the long-term micronutrient needs in children with SBS vary, based on their clinical and anatomical characteristics. Our study aimed to review the clinical course and identify high risk patient groups for prolonged PS and long-term micronutrient supplementation. METHODS: A retrospective review was conducted on electronic medical records of children with SBS and chronic intestinal failure who were enrolled in the multidisciplinary intestinal rehabilitation program at Manchester Children's Hospital, UK. Children were included in the review if they required PN for more than 60 days out of 74 consecutive days and had at least 3 years of follow-up. Statistical analysis was performed using IBM SPSS Statistics 24.0. RESULTS: 40 children with SBS achieved enteral autonomy (EA) and 14 remained dependent on PS after 36 months of follow up. Necrotizing enterocolitis was the most common cause for intestinal resection (38.9%) followed by gastroschisis (22.2%), malrotation with volvulus (20.4%), segmental volvulus (9.3%) and long segment Hirschsprung disease (1.9%). Those who achieved EA had significantly longer intestinal length 27.5% (15.0-39.3) than those who remained on PS 6.0% (1.5-12.5) (p < 0.001). Type I SBS was only found in the PS cohort. Median PN dependence was 10.82 months [IQR 5.73-20.78]. Congenital diagnosis was associated with longer PN dependence (21.0 ± 20.0) than acquired (8.7 ± 7.8 months), (p = 0.02). The need for micronutrient supplementation was assessed after the transition to EA; 87.5% children had at least one micronutrient depletion, most commonly Vitamin D (64.1%), followed by iron (48.7%), Vitamin B12 (34.2%), and vitamin E (28.6%). Iron deficiency and vitamin A depletion were correlated with longer PS after multivariate analysis (OR: 1.103, 1.006-1.210, p = 0.037 and OR: 1.048, 0.998-1.102, p = 0.062 respectively). CONCLUSION: In our cohort, small bowel length was the main predictor for EA. Children on longer PS, had more often a congenital cause of resection and were at risk for micronutrient deficiencies in EA.


Assuntos
Insuficiência Intestinal , Micronutrientes , Nutrição Parenteral , Síndrome do Intestino Curto , Oligoelementos , Criança , Humanos , Recém-Nascido , Enteropatias/etiologia , Enteropatias/terapia , Insuficiência Intestinal/etiologia , Insuficiência Intestinal/terapia , Volvo Intestinal/complicações , Micronutrientes/administração & dosagem , Micronutrientes/deficiência , Micronutrientes/uso terapêutico , Estudos Retrospectivos , Síndrome do Intestino Curto/etiologia , Síndrome do Intestino Curto/terapia , Oligoelementos/administração & dosagem , Oligoelementos/deficiência , Oligoelementos/uso terapêutico , Nutrição Parenteral/métodos
17.
Chem Senses ; 37(6): 553-66, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22473924

RESUMO

Olfaction begins when an animal draws odorant-laden air into its nasal cavity by sniffing, thus transporting odorant molecules from the external environment to olfactory receptor neurons (ORNs) in the sensory region of the nose. In the dog and other macrosmatic mammals, ORNs are relegated to a recess in the rear of the nasal cavity that is comprised of a labyrinth of scroll-like airways. Evidence from recent studies suggests that nasal airflow patterns enhance olfactory sensitivity by efficiently delivering odorant molecules to the olfactory recess. Here, we simulate odorant transport and deposition during steady inspiration in an anatomically correct reconstructed model of the canine nasal cavity. Our simulations show that highly soluble odorants are deposited in the front of the olfactory recess along the dorsal meatus and nasal septum, whereas moderately soluble and insoluble odorants are more uniformly deposited throughout the entire olfactory recess. These results demonstrate that odorant deposition patterns correspond with the anatomical organization of ORNs in the olfactory recess. Specifically, ORNs that are sensitive to a particular class of odorants are located in regions where that class of odorants is deposited. The correlation of odorant deposition patterns with the anatomical organization of ORNs may partially explain macrosmia in the dog and other keen-scented species.


Assuntos
Simulação por Computador , Cavidade Nasal/metabolismo , Odorantes , Olfato/fisiologia , Movimentos do Ar , Animais , Transporte Biológico , Cães , Odorantes/análise
18.
Pulm Pharmacol Ther ; 25(4): 293-302, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22659538

RESUMO

Here we describe the pre-clinical pharmacological profile of AZD9708, a novel long-acting ß(2)-adrenoceptor agonist that has potential as a once-daily therapy for asthma and chronic obstructive pulmonary disease (COPD). AZD9708 is a potent and selective agonist at the human ß(2)-adrenoceptor, with selectivity over human ß(1)- and ß(3)-adrenoceptors of >500 and >24 fold, respectively. AZD9708 relaxes carbachol-induced contraction of human bronchial rings with a time to 90% of maximal relaxation of 13-20 min, similar to that seen with formoterol and quicker than salmeterol. In anesthetized guinea pigs, AZD9708 provides significant protection against histamine-induced airway constriction at 24 h after intratracheal and nebulized doses. This is longer than with intratracheal salmeterol, which is bronchoprotective for approximately 8 h, and formoterol, which is bronchoprotective for 8 and 12 h following nebulized and intratracheal dosing, respectively. AZD9708 also shows the potential for a greater therapeutic margin than widely used ß(2)-adrenoceptor agonists such as formoterol. At a defined efficacy dose that provides 80% bronchoprotection (ED(80)), formoterol leads to a decrease in blood potassium levels in guinea pigs, whilst AZD9708 is not associated with significant reductions in potassium levels at doses up to 7 times the ED(80). [(14)C]AZD9708 is associated with extensive protein binding in both human (mean 1.0% free) and rat (mean 2.6% free) plasma. This pharmacological profile indicates the potential of AZD9708 to become an important addition to the range of bronchodilators available for the treatment of patients with obstructive airways disease.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Benzotiazóis/farmacologia , beta-Alanina/análogos & derivados , Monofosfato de Adenosina/metabolismo , Albuterol/análogos & derivados , Albuterol/farmacologia , Animais , Asma/tratamento farmacológico , Asma/fisiopatologia , Proteínas Sanguíneas/metabolismo , Brônquios/efeitos dos fármacos , Broncodilatadores/farmacologia , Etanolaminas/farmacologia , Fumarato de Formoterol , Cobaias , Humanos , Masculino , Relaxamento Muscular/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Receptores Adrenérgicos beta 2/metabolismo , Xinafoato de Salmeterol , Fatores de Tempo , beta-Alanina/farmacologia
19.
J Exp Psychol Gen ; 151(5): 1154-1177, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34694858

RESUMO

Sharing misinformation can be catastrophic, especially during times of national importance. Typically studied in political contexts, the sharing of fake news has been positively linked with conservative political ideology. However, such sweeping generalizations run the risk of increasing already rampant political polarization. We offer a more nuanced account by proposing that the sharing of fake news is largely driven by low conscientiousness conservatives. At high levels of conscientiousness there is no difference between liberals and conservatives. We find support for our hypotheses in the contexts of COVID-19, political, and neutral news across eight studies (six preregistered; two conceptual replications) with 4,642 participants and 91,144 unique participant-news observations. A general desire for chaos explains the interactive effect of political ideology and conscientiousness on the sharing of fake news. Furthermore, our findings indicate the inadequacy of fact-checker interventions to deter the spread of fake news. This underscores the challenges associated with tackling fake news, especially during a crisis like COVID-19 where misinformation impairs the ability of governments to curtail the pandemic. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Assuntos
COVID-19 , Pandemias , Desinformação , Humanos , Personalidade , Política
20.
J Pediatr ; 159(2): 256-61.e2, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21429515

RESUMO

OBJECTIVE: To determine whether pulmonary function decreases as a function of severity of pectus excavatum, and whether reduced function is restrictive or obstructive in nature in a large multicenter study. STUDY DESIGN: We evaluated preoperative spirometry data in 310 patients and lung volumes in 218 patients aged 6 to 21 years at 11 North American centers. We modeled the impact of the severity of deformity (based on the Haller index) on pulmonary function. RESULTS: The percentages of patients with abnormal forced vital capacity (FVC), forced expiratory volume in 1 second (FEV(1)), forced expiratory flow from 25% exhalation to 75% exhalation, and total lung capacity findings increased with increasing Haller index score. Less than 2% of patients demonstrated an obstructive pattern (FEV(1)/FVC <67%), and 14.5% demonstrated a restrictive pattern (FVC and FEV(1) <80% predicted; FEV(1)/FVC >80%). Patients with a Haller index of 7 are >4 times more likely to have an FVC of ≤80% than those with a Haller index of 4, and are also 4 times more likely to exhibit a restrictive pulmonary pattern. CONCLUSIONS: Among patients presenting for surgical repair of pectus excavatum, those with more severe deformities have a much higher likelihood of decreased pulmonary function with a restrictive pulmonary pattern.


Assuntos
Fluxo Expiratório Forçado/fisiologia , Tórax em Funil/diagnóstico , Insuficiência Respiratória/etiologia , Capacidade Vital/fisiologia , Adolescente , Criança , Progressão da Doença , Feminino , Seguimentos , Tórax em Funil/complicações , Tórax em Funil/fisiopatologia , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Radiografia Torácica , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/fisiopatologia , Índice de Gravidade de Doença , Espirometria , Tomografia Computadorizada por Raios X , Adulto Jovem
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