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1.
SLAS Discov ; 28(5): 223-232, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37307989

RESUMEN

Small molecules that bind to allosteric sites on target proteins to alter protein function are highly sought in drug discovery. High-throughput screening (HTS) assays are needed to facilitate the direct discovery of allosterically active compounds. We have developed technology for high-throughput time-resolved fluorescence lifetime detection of fluorescence resonance energy transfer (FRET), which enables the detection of allosteric modulators by monitoring changes in protein structure. We tested this approach at the industrial scale by adapting an allosteric FRET sensor of cardiac myosin to high-throughput screening (HTS), based on technology provided by Photonic Pharma and the University of Minnesota, and then used the sensor to screen 1.6 million compounds in the HTS facility at Bristol Myers Squibb. The results identified allosteric activators and inhibitors of cardiac myosin that do not compete with ATP binding, demonstrating high potential for FLT-based drug discovery.


Asunto(s)
Transferencia Resonante de Energía de Fluorescencia , Ensayos Analíticos de Alto Rendimiento , Ensayos Analíticos de Alto Rendimiento/métodos , Transferencia Resonante de Energía de Fluorescencia/métodos , Miosinas Cardíacas , Descubrimiento de Drogas/métodos
2.
J Environ Manage ; 317: 115411, 2022 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-35751248

RESUMEN

Coastal suburban watersheds are under heavy pressure from human activity. This pressure has yielded an extensive effort to protect, mitigate, and restore watershed ecosystem services. Assessment of restoration investments would be greatly improved by a standard approach for estimating change in ecosystem service production combined with a well-defined baseline for assessment of restoration effects. Here we take a model-based approach to both objectives by applying two established ecosystem service models in a representative coastal watershed. This watershed has undergone extensive suburbanization resulting in a loss of ecosystem services, which has resulted in heavy restoration investments. We used models to estimate loss of the ecosystem services; clean air, clean water, stable climate, and water storage resulting from suburbanization. We then applied these model-based estimates as a baseline for assessment of restoration focusing on the appropriate restoration scale and considering downstream watershed impacts. The results suggest that losses of ecosystem services, such as flood water storage, from suburbanization have been extensive since 2001, but a comparison of restoration value suggests that restoration has been effective in recouping ecosystem services in some but not all local regions suggesting there are trade-offs to be made in these efforts. These benefits were most evident for the services of clean water and water storage. Models can inform decisions by clarifying what has been lost and estimating what can be regained through restoration action. The former sets a baseline for the latter and allows for a functional equivalency approach to assessment.


Asunto(s)
Ecosistema , Agua , Conservación de los Recursos Naturales/métodos , Humanos
3.
J Neonatal Perinatal Med ; 14(4): 583-590, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33843700

RESUMEN

BACKGROUND: Micro-premature newborns, gestational age (GA) ≤ 25 weeks, have high rates of mortality and morbidity. Literature has shown improving outcomes for extremely low gestational age newborns (ELGANs) GA ≤ 29 weeks, but few studies have addressed outcomes of ELGANs ≤ 25 weeks. OBJECTIVE: To evaluate the trends in outcomes for ELGANs born in New Jersey, from 2000 to 2018 and to compare two subgroups: GA 23 to 25 weeks (E1) and GA 26 to 29 weeks (E2). METHODS: Thirteen NICUs in NJ submitted de-identified data. Outcomes for mortality and morbidity were calculated. RESULTS: Data from 12,707 infants represents the majority of ELGANs born in NJ from 2000 to 2018. There were 3,957 in the E1 group and 8,750 in the E2 group. Mortality decreased significantly in both groups; E1, 43.2% to 30.2% and E2, 7.6% to 4.5% over the 19 years. The decline in E1 was significantly greater than in E2. Most morbidities also showed significant improvement over time in both groups. Survival without morbidity increased from 14.5% to 30.7% in E1s and 47.2% to 69.9% in E2s. Similar findings held for 501-750 and 751-1000g birth weight strata. CONCLUSIONS: Significant declines in both mortality and morbidity have occurred in ELGANs over the last two decades. These rates of improvements for the more immature ELGANs of GA 230 to 256 weeks were greater than for the more mature group in several outcomes. While the rates of morbidity and mortality remain high, these results validate current efforts to support the micro-premature newborn.


Asunto(s)
Enfermedades del Prematuro , Edad Gestacional , Humanos , Lactante , Recién Nacido de Bajo Peso , Recién Nacido , Recien Nacido Prematuro , Morbilidad , New Jersey/epidemiología
4.
BMJ Open ; 11(3): e045384, 2021 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-33727275

RESUMEN

OBJECTIVES: Since its emergence in late 2019, SARS-CoV-2 has caused a global pandemic that has significantly challenged healthcare systems. Healthcare workers have previously been shown to have experienced higher rates of infection than the general population. We aimed to assess the extent of infection in staff working in our healthcare setting. DESIGN: A retrospective analysis of antibody results, compared with staff demographic data, and exposure to patients with COVID-19 infection. SETTING: A large teaching hospital in the North West of England. PARTICIPANTS: 4474 staff in diverse clinical and non-patient facing roles who volunteered for SARS-CoV-2 antibody testing by the Roche Elecsys assay between 29 May and 4 July 2020. RESULTS: Seroprevalence was 17.4%. Higher rates were seen in Asian/Asian British (OR 1.61, 95% CI 1.27 to 2.04) and Black/Black British (OR 2.08, 95% CI 1.25 to 3.45) staff. Staff working in any clinical location were more likely to be seropositive (OR 2.68, 95% 2.27 to 3.15). Staff were at an increased risk of seropositivity as the 'per 100 COVID-19 bed-days change' increased in the clinical area in which they worked (OR 1.12, 95% 1.10 to 1.14). Staff working in critical care were no more likely to have detectable antibodies than staff working in non-clinical areas. Symptoms compatible with COVID-19 were reported in 41.8% and antibodies were detected in 30.7% of these individuals. In staff who reported no symptoms, antibodies were detected in 7.7%. In all staff who had detectable antibodies, 25.2% reported no symptoms. CONCLUSIONS: Staff working in clinical areas where patients with COVID-19 were nursed were more likely to have detectable antibodies. The relationship between seropositivity in healthcare workers and the increase in 'per 100 COVID-19 bed-days' of the area in which they worked, although statistically significant, was weak, suggesting other contributing factors to the risk profile. Of staff with detectable antibodies and therefore evidence of prior infection, a quarter self-reported that they had experienced no compatible symptoms. This has implications for potential unrecorded transmission in both staff and patients.


Asunto(s)
COVID-19/diagnóstico , Personal de Salud/estadística & datos numéricos , Estudios Seroepidemiológicos , COVID-19/sangre , Inglaterra/epidemiología , Hospitales de Enseñanza , Humanos , Prevalencia , Estudios Retrospectivos
5.
Philos Trans A Math Phys Eng Sci ; 378(2184): 20200031, 2020 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-33040651

RESUMEN

Argon fluoride (ArF) is currently the shortest wavelength laser that can credibly scale to the energy and power required for high gain inertial fusion. ArF's deep ultraviolet light and capability to provide much wider bandwidth than other contemporary inertial confinement fusion (ICF) laser drivers would drastically improve the laser target coupling efficiency and enable substantially higher pressures to drive an implosion. Our radiation hydrodynamics simulations indicate gains greater than 100 are feasible with a sub-megajoule ArF driver. Our laser kinetics simulations indicate that the electron beam-pumped ArF laser can have intrinsic efficiencies of more than 16%, versus about 12% for the next most efficient krypton fluoride excimer laser. We expect at least 10% 'wall plug' efficiency for delivering ArF light to target should be achievable using solid-state pulsed power and efficient electron beam transport to the laser gas that was demonstrated with the U.S. Naval Research Laboratory's Electra facility. These advantages could enable the development of modest size and lower cost fusion power plant modules. This would drastically change the present view on inertial fusion energy as being too expensive and the power plant size too large. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 1)'.

6.
Clin Neurophysiol ; 130(11): 2019-2025, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31539768

RESUMEN

OBJECTIVE: Increasingly, serotonin selective reuptake inhibitor (SSRI) medications are prescribed in pregnancy. These medications pass freely into the developing fetus but little is known about their effect on brain development in humans. In this study we determine if prenatal maternal depression and SSRI medication change the EEG infant delta brush bursts which are an early marker of normal brain maturation. METHODS: We measured delta brush bursts from the term infants of three groups of mothers (controls (N = 52), depressed untreated (N = 15), and those taking serotonin SSRI medication (N = 10). High density EEGs were obtained during sleep at an average age of 44 weeks post conceptional age. We measured the rate of occurrence, brush amplitude, oscillation frequency and duration of the bursts. RESULTS: Compared to infants of control mothers, the parameters of delta brush bursts of the offspring of depressed and SSRI-using mothers are significantly altered: burst amplitude is decreased; the oscillation frequency increased, and the duration increased (SSRI only). These significant differences were found during both sleep states. CONCLUSIONS: Electrocortical bursting activity (i.e. delta brushes) is known to play an important role in early central nervous system (CNS) synaptic formation and function. SIGNIFICANCE: Maternal depression or SSRI use may alter brain function in their offspring.


Asunto(s)
Encéfalo/fisiopatología , Trastorno Depresivo/tratamiento farmacológico , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Adulto , Encéfalo/efectos de los fármacos , Trastorno Depresivo/fisiopatología , Electroencefalografía , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Complicaciones del Embarazo/tratamiento farmacológico , Complicaciones del Embarazo/fisiopatología , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Adulto Joven
8.
Contemp Clin Trials ; 62: 159-167, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28887069

RESUMEN

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of hospitalizations. Interventional studies focusing on the hospital-to-home transition for COPD patients are few. In the BREATHE (Better Respiratory Education and Treatment Help Empower) study, we developed and tested a patient and family-centered transitional care program that helps prepare hospitalized COPD patients and their family caregivers to manage COPD at home. METHODS: In the study's initial phase, we co-developed the BREATHE transitional care program with COPD patients, family-caregivers, and stakeholders. The program offers tailored services to address individual patients' needs and priorities at the hospital and for 3months post discharge. We tested the program in a single-blinded RCT with 240 COPD patients who were randomized to receive the program or 'usual care'. Program participants were offered the opportunity to invite a family caregiver, if available, to enroll with them into the study. The primary outcomes were the combined number of COPD-related hospitalizations and Emergency Department (ED) visits per participant at 6months post discharge, and the change in health-related quality of life over the 6months study period. Other measures include 'all cause' hospitalizations and ED visits; patient activation; self-efficacy; and, self-care behaviors. DISCUSSION: Unlike 1month transitional care programs that focus on patients' post-acute care needs, the BREATHE program helps hospitalized COPD patients manage the post discharge period as well as prepare them for long term self-management of COPD. If proven effective, this program may offer a timely solution for hospitals in their attempts to reduce COPD rehospitalizations.


Asunto(s)
Servicio de Urgencia en Hospital/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Atención Dirigida al Paciente/organización & administración , Cuidado de Transición/organización & administración , Factores de Edad , Anciano , Servicios de Salud Comunitaria/organización & administración , Familia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Grupo de Atención al Paciente/organización & administración , Educación del Paciente como Asunto/organización & administración , Proyectos Piloto , Enfermedad Pulmonar Obstructiva Crónica/terapia , Calidad de Vida , Proyectos de Investigación , Autocuidado , Autoeficacia , Factores Sexuales , Método Simple Ciego , Factores Socioeconómicos
9.
J Genet Couns ; 26(3): 355-360, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28236280

RESUMEN

As the demand for evidence to support the value of genetic counseling increases, it is critical that reporting of genetic counseling interventions in research and other types of studies (e.g. process improvement or service evaluation studies) adopt greater rigor. As in other areas of healthcare, the appraisal, synthesis, and translation of research findings into genetic counseling practice are likely to be improved if clear specifications of genetic counseling interventions are reported when studies involving genetic counseling are published. To help improve reporting practices, the National Society of Genetic Counselors (NSGC) convened a task force in 2015 to develop consensus standards for the reporting of genetic counseling interventions. Following review by the NSGC Board of Directors, the NSGC Practice Guidelines Committee and the editorial board of the Journal of Genetic Counseling, 23 items across 8 domains were proposed as standards for the reporting of genetic counseling interventions in the published literature (GCIRS: Genetic Counseling Intervention Reporting Standards). The authors recommend adoption of these standards by authors and journals when reporting studies involving genetic counseling interventions.


Asunto(s)
Comités Consultivos , Asesoramiento Genético/normas , Informe de Investigación/normas , Sociedades Médicas , Femenino , Humanos , Masculino , Estados Unidos
10.
J Vet Pharmacol Ther ; 40(4): 356-362, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27654900

RESUMEN

Twelve healthy swine were dosed with penicillin G intramuscularly. Fluids and tissues samples were collected at the end of two periods of general anesthesia, performed 24 h apart. Tissue samples were collected by minimally invasive laparoscopy under general anesthesia at 8 and 28 h postdose. Four nonanesthetized, penicillin-treated pigs were euthanized at 8 h postdose, and a second set of four similarly treated control pigs were sacrificed 28 h postdose. Liver penicillin tissue concentrations from animals that underwent anesthesia and laparoscopic tissue collection had tissue concentrations that were higher than nonanesthetized pigs at both time points. Urine, plasma, kidney, skeletal, and cardiac muscle showed no differences between the two groups. Laparoscopic tissue collection under general anesthesia in swine induces physiological changes that cause alterations in tissue pharmacokinetics not seen in conscious animals.


Asunto(s)
Isoflurano/farmacología , Penicilinas/metabolismo , Porcinos/metabolismo , Anestesia General , Anestesia por Inhalación/veterinaria , Anestésicos por Inhalación , Animales , Interacciones Farmacológicas , Hígado
11.
Public Health ; 141: 232-240, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27932008

RESUMEN

BACKGROUND: Smoking, insufficient physical activity (PA), sedentary behaviour (SB) and obesity are leading risk factors for morbidity and premature mortality. Few studies examining the relationship between these behavioural risk factors and quitting behaviours among cohorts of smokers have been published. PURPOSE: The goals of this study are to examine the cross-sectional relationships among behavioural health risk factors (insufficient PA, SB and obesity) and past year quitting behaviours within a sample of smokers. METHODS: The California Smokers Cohort, conducted from 2011 through 2013, is a population-based survey of adult smokers in California. Using follow-up data (n = 1050), participants' self-reported health behaviours and past year quitting behaviours were examined in univariate analyses and multivariate logistic regression analyses controlling for demographic covariates. RESULTS: In univariate analyses examining health behaviours among smokers, all three health behaviours examined (PA, SB and obesity) were related, and significantly more obese smokers with high PA and low SB reported a ≥20% smoking rate reduction than smokers with other combinations of health behaviours (48.8%, Chi-squared = 4.765, P = 0.045). In multivariate models adjusted for sociodemographic characteristics, obese smokers (odds ratio [OR] = 1.450, 95% confidence interval [CI]: 1.088-1.932, P = 0.011) and smokers with higher levels of PA (OR = 1.448, 95% CI: 1.111-1.887, P = 0.006) were more likely to report a past year ≥24-hour quit attempt regardless of SB, and obese smokers (OR = 1.760, 95% CI: 1.095-2.828, P = 0.019) were more likely to report being quit for ≥30 days regardless of PA and SB. CONCLUSIONS: Overall, the results demonstrated that more physically active and obese smokers were more likely to report positive strides towards quitting. These findings support the potential positive effect of addressing multiple health behaviours along with smoking.


Asunto(s)
Ejercicio Físico/psicología , Obesidad/psicología , Conducta Sedentaria , Cese del Hábito de Fumar/psicología , Fumar/psicología , Adulto , California/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Fumar/epidemiología , Cese del Hábito de Fumar/estadística & datos numéricos
12.
J Vet Pharmacol Ther ; 39(6): 602-611, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27189015

RESUMEN

Eighteen Holstein dairy cows ranging in body weight from 500-700 kg and with an average milk yield of 37 ± 6 kg/day were used to investigate the depletion of florfenicol (FFL) in milk and plasma of dairy cows. Three groups of six were administered FFL: Group A, intramammary (IMM) infusion of ~2.5 mg FFL/kg BW at three consecutive milking intervals (total amount of ~7.5 mg/kg BW); Group B, one IMM infusion (20 mg/kg BW) into one quarter and Group C, one subcutaneous (SC) treatment (40 mg/kg BW). IMM infusions were into the right front quarter. Cows were milked daily at 06:00 and 18:00 h. The highest concentrations (Cmax ) and time to Cmax (Tmax ) were: 1.6 ± 2.2 µg·FFL/mL milk at 22 h (Group A), 5.5 ± 3.6 µg·FFL/mL milk at 12 h (Group B), and 1.7 ± 0.4 µg·FFL/mL milk at 12 h (Group C). The half-lives (t1/2 ) were ~19, 5.5, and 60 h, for Groups A, B, and C, respectively. FFL was below the limit of detection (LOD) by 60 h in three Group B cows, but above the LOD at 72, 84, and 120 h in three cows. FFL was above the LOD in milk from Group C's cows for 432-588 h. Plasma values followed the same trends as milk. The results demonstrate that IMM-infused FFL is bioavailable and below the LOD within 72-120 h. The concentration of FFL was detectable in both plasma and milk over the course of 2-3 weeks after SC administration. The absence of residue depletion data presents problems in determining safe levels of FFL residues in milk and edible tissues. The data presented here must not be construed as approval for extra-label use in food animals.


Asunto(s)
Antibacterianos/farmacocinética , Bovinos/sangre , Glándulas Mamarias Animales/metabolismo , Tianfenicol/análogos & derivados , Animales , Antibacterianos/administración & dosificación , Antibacterianos/química , Bovinos/metabolismo , Vías de Administración de Medicamentos , Femenino , Leche/química , Tianfenicol/administración & dosificación , Tianfenicol/química , Tianfenicol/farmacocinética
13.
FEMS Microbiol Ecol ; 92(4): fiw028, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26906098

RESUMEN

The phylogenetic affiliations of organisms responsible for aerobic CO oxidation in hypersaline soils and sediments were assessed using media containing 3.8 M NaCl. CO-oxidizing strains of the euryarchaeotes, Haloarcula, Halorubrum, Haloterrigena and Natronorubrum, were isolated from the Bonneville Salt Flats (UT) and Atacama Desert salterns (Chile). A halophilic euryarchaeote, Haloferax strain Mke2.3(T), was isolated from Hawai'i Island saline cinders. Haloferax strain Mke2.3(T) was most closely related to Haloferax larsenii JCM 13917(T) (97.0% 16S rRNA sequence identity). It grew with a limited range of substrates, and oxidized CO at a headspace concentration of 0.1%. However, it did not grow with CO as a sole carbon and energy source. Its ability to oxidize CO, its polar lipid composition, substrate utilization and numerous other traits distinguished it from H. larsenii JCM 13917(T), and supported designation of the novel isolate as Haloferax namakaokahaiae Mke2.3(T), sp. nov (= DSM 29988, = LMG 29162). CO oxidation was also documented for 'Natronorubrum thiooxidans' HG1 (Sorokin, Tourova and Muyzer 2005), N. bangense (Xu, Zhou and Tian 1999) and N. sulfidifaciens AD2(T) (Cui et al. 2007). Collectively, these results established a previously unsuspected capacity for extremely halophilic aerobic CO oxidation, and indicated that the trait might be widespread among the Halobacteriaceae, and occur in a wide range of hypersaline habitats.


Asunto(s)
Monóxido de Carbono/metabolismo , Haloferax , Salinidad , Cloruro de Sodio/metabolismo , Microbiología del Suelo , Aerobiosis , Chile , ADN Ribosómico/genética , Genoma Arqueal/genética , Sedimentos Geológicos/microbiología , Haloferax/genética , Haloferax/aislamiento & purificación , Haloferax/metabolismo , Oxidación-Reducción , Filogenia , ARN Ribosómico 16S/genética , Suelo/química
14.
J Vet Pharmacol Ther ; 39(2): 131-7, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26471945

RESUMEN

This study evaluated the impact of the ABCB1-1Δ mutation in Collies which exhibited toxicity toward ivermectin, on changes in gene expression when given the unrelated ABCB1 substrate loperamide, to identify potential biomarkers predictive of drug safety. Thirty-two healthy intact Collies consisting of dogs with either a wild-type, heterozygous mutant, or homozygous mutant genotype were used. Whole blood samples were collected from Collies at 0 or 5 h following administration of loperamide at a dose of 0.10 mg/kg. Whole-genome gene expression microarray was conducted to examine for changes in gene expression. Microarray analysis identified loperamide-induced changes in gene expression which were specifically associated with ivermectin-sensitive phenotypes in Collies possessing the ABCB1-1Δ mutation. Gene pathway analysis further demonstrated that the altered genes are involved in immunological disease, cell death and survival, and cellular development. Thirteen genes, including CCL8 and IL-8, were identified. Collie dogs harboring ABCB1-1Δ mutation which also exhibited toxicity toward ivermectin demonstrated systematic responses following loperamide treatment exhibited by altered expression of genes involved in immune and inflammatory signaling pathways. Genes such as CCL8 and IL-8 are potential biomarkers in whole blood that may predict the safety of loperamide in dogs with ABCB1-1∆ mutation associated with ivermectin sensitivity.


Asunto(s)
Enfermedades de los Perros/inducido químicamente , Hipersensibilidad a las Drogas/veterinaria , Regulación de la Expresión Génica/efectos de los fármacos , Inflamación/veterinaria , Ivermectina/efectos adversos , Loperamida/farmacología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Animales , Enfermedades de los Perros/sangre , Enfermedades de los Perros/genética , Enfermedades de los Perros/metabolismo , Perros , Femenino , Regulación de la Expresión Génica/inmunología , Inflamación/inducido químicamente , Inflamación/genética , Inflamación/metabolismo , Masculino , Mutación
15.
Oncogene ; 35(16): 2062-74, 2016 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-26234678

RESUMEN

Tat-interacting protein of 60 kDa (TIP60) is an essential lysine acetyltransferase implicated in transcription, DNA damage response and apoptosis. TIP60 protein expression is reduced in cancers. In cervical cancers, human papillomavirus (HPV) E6 oncogene targets cellular p53, Bak and some of the PDZ domain-containing proteins for proteasome-mediated degradation through E6AP ligase. Recently, E6 oncogene from high-risk and low-risk categories was also shown to target TIP60. However, the molecular mechanisms and whether destabilization of TIP60 contributes to HPV E6-mediated transformation remain unanswered. Our proteomic analyses revealed EDD1 (E3 identified by differential display), an E3 ligase generally overexpressed in cancers as a novel interacting partner of TIP60. By investigating protein turnover and ubiquitination assays, we show that EDD1 negatively regulates TIP60's stability through the proteasome pathway. Strikingly, HPV E6 uses this function of EDD1 to destabilize TIP60. Colony-formation assays and soft agar assays show that gain of function of TIP60 or depletion of EDD1 in HPV-positive cervical cancer cells significantly inhibits cell growth in vitro. This phenotype is strongly supported by the in-vivo studies where re-activation of TIP60 in cervical cancer cells dramatically reduces tumor formation. In summary, we have discovered a novel ligase through which E6 destabilizes TIP60. Currently, in the absence of an effective therapeutic vaccine for malignant cervical cancers, cervical cancer still remains to be a major disease burden. Hence, our studies implying a distinct tumor suppressor role for TIP60 in cervical cancers show that reactivation of TIP60 could be of therapeutic value.


Asunto(s)
Histona Acetiltransferasas/metabolismo , Proteínas Oncogénicas Virales/genética , Oncogenes , Papillomaviridae/genética , Ubiquitina-Proteína Ligasas/metabolismo , División Celular/genética , Línea Celular , Genes Supresores de Tumor , Humanos , Lisina Acetiltransferasa 5 , Unión Proteica , Proteómica , Ubiquitina-Proteína Ligasas/genética
16.
Plant Dis ; 100(12): 2442-2447, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30686171

RESUMEN

Antimicrobial activity of experimental formulations of two structurally different nano-zinc oxide materials, plate-like Zinkicide SG4 and particulate Zinkicide SG6, was evaluated against Xanthomonas citri subsp. citri, the cause of citrus canker. In vitro assay demonstrated Zinkicide SG4 had a twofold lower minimum inhibitory concentration (MIC) against Escherichia coli and X. alfalfae subsp. citrumelonis (62.5 to 250 µg/ml) compared with copper sulfate (250 µg/ml), copper hydroxide (250 to 500 µg/ml), or cuprous oxide/zinc oxide (125 to 250 µg/ml). Zinkicide SG6 had a sevenfold to eightfold lower MIC against Escherichia coli and X. alfalfae subsp. citrumelonis (31 to 250 µg/ml). Leaves of sweet orange (Citrus sinensis) and fruit of 'Ruby Red' grapefruit (C. paradisi) were evaluated for citrus canker disease control. A greenhouse assay with foliage demonstrated that spray treatment with Zinkicide reduced citrus canker lesion development after injection-infiltration of X. citri subsp. citri into the leaf intercellular space. In field trials conducted in Southeast Florida in 2014 and 2015, Zinkicide SG4 and SG6 reduction of grapefruit canker incidence exceeded that of cuprous oxide and cuprous oxide/zinc oxide bactericides. Zinkicide formulations were also effective against the fungal diseases, citrus scab (Elsinoe fawcetti) and melanose (Diaporthe citri), on grapefruit. No sign of phytotoxicity to the fruit rind was observed during either season. Antimicrobial activity of Zinkicide for protection of leaves and fruit against X. citri subsp. citri was comparable or exceeded that for commercial copper and zinc oxide formulations which may be attributed to translaminar movement of Zinkicide.

17.
Acta Paediatr ; 104(7): 670-7, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25772627

RESUMEN

AIM: To assess the impact of Family Nurture Intervention (FNI) on cortical function in preterm infants at term age. METHODS: Family Nurture Intervention is a NICU-based intervention designed to establish emotional connection between mothers and preterm infants. Infants born at 26-34 weeks postmenstrual age (PMA) were divided into two groups, standard care (SC, N = 49) and FNI (FNI, N = 56). Infants had EEG recordings of ~one hour duration with 124 lead nets between 37 and 44 weeks PMA. Coherence was measured between all pairs of electrodes in ten frequency bands. Data were summarised both within and between 12 regions during two sleep states (active, quiet). RESULTS: Coherence levels were negatively correlated with PMA age in both groups. As compared to SC infants, FNI infants showed significantly lower levels of EEG coherence (1-18 Hz) largely within and between frontal regions. CONCLUSION: Coherence in FNI infants was decreased in regions where we previously found robust increases in EEG power. As coherence decreases with age, results suggest that FNI may accelerate brain maturation particularly in frontal brain regions, which have been shown in research by others to be involved in regulation of attention, cognition and emotion regulation; domains deficient in preterm infants.


Asunto(s)
Corteza Cerebral/fisiopatología , Cuidados Críticos , Enfermedades del Prematuro/terapia , Conducta Materna , Madres/psicología , Relaciones Padres-Hijo , Factores de Edad , Electroencefalografía , Emociones , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/fisiopatología , Enfermedades del Prematuro/psicología , Masculino , Sueño
18.
Phys Rev Lett ; 113(2): 021301, 2014 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-25062161

RESUMEN

Gravitational lensing due to the large-scale distribution of matter in the cosmos distorts the primordial cosmic microwave background (CMB) and thereby induces new, small-scale B-mode polarization. This signal carries detailed information about the distribution of all the gravitating matter between the observer and CMB last scattering surface. We report the first direct evidence for polarization lensing based on purely CMB information, from using the four-point correlations of even- and odd-parity E- and B-mode polarization mapped over ∼30 square degrees of the sky measured by the POLARBEAR experiment. These data were analyzed using a blind analysis framework and checked for spurious systematic contamination using null tests and simulations. Evidence for the signal of polarization lensing and lensing B modes is found at 4.2σ (stat+sys) significance. The amplitude of matter fluctuations is measured with a precision of 27%, and is found to be consistent with the Lambda cold dark matter cosmological model. This measurement demonstrates a new technique, capable of mapping all gravitating matter in the Universe, sensitive to the sum of neutrino masses, and essential for cleaning the lensing B-mode signal in searches for primordial gravitational waves.

19.
J Breath Res ; 8(2): 027109, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24861817

RESUMEN

Lung cancer is the leading cause of cancer deaths. Unfortunately, lung cancer is often diagnosed only when it becomes symptomatic or at an advanced stage when few treatment options are available. Hence, a diagnostic test suitable for screening widespread populations is required to enable earlier diagnosis. Analysis of exhaled breath provides a non-invasive method for early detection of lung cancer. Analysis of volatile organic compounds (VOCs) by various mass spectral techniques has identified potential biomarkers of disease. Nevertheless, the metabolic origins and the disease specificity of VOCs need further elucidation. Cell culture metabolomics can be used as a bottom-up approach to identify biomarkers of pathological conditions and can also be used to study the metabolic pathways that produce such compounds. This paper summarizes the current knowledge of lung cancer biomarkers in exhaled breath and emphasizes the critical role of cell culture conditions in determining the VOCs produced in vitro. Hypoxic culture conditions more closely mimic the conditions of cancer cell growth in vivo. We propose that since hypoxia influences cell metabolism and so potentially the VOCs that the cancer cells produce, the cell culture metabolomics projects should consider culturing cancer cells in hypoxic conditions.


Asunto(s)
Técnicas de Cultivo de Célula , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Metabolómica/métodos , Biomarcadores/análisis , Biomarcadores/metabolismo , Pruebas Respiratorias , Técnicas de Cultivo de Célula/métodos , Hipoxia de la Célula/fisiología , Humanos , Neoplasias Pulmonares/patología , Compuestos Orgánicos Volátiles/análisis , Compuestos Orgánicos Volátiles/metabolismo
20.
Phys Rev Lett ; 112(13): 131302, 2014 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-24745402

RESUMEN

We reconstruct the gravitational lensing convergence signal from cosmic microwave background (CMB) polarization data taken by the Polarbear experiment and cross-correlate it with cosmic infrared background maps from the Herschel satellite. From the cross spectra, we obtain evidence for gravitational lensing of the CMB polarization at a statistical significance of 4.0σ and indication of the presence of a lensing B-mode signal at a significance of 2.3σ. We demonstrate that our results are not biased by instrumental and astrophysical systematic errors by performing null tests, checks with simulated and real data, and analytical calculations. This measurement of polarization lensing, made via the robust cross-correlation channel, not only reinforces POLARBEAR auto-correlation measurements, but also represents one of the early steps towards establishing CMB polarization lensing as a powerful new probe of cosmology and astrophysics.

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