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1.
Catheter Cardiovasc Interv ; 103(2): 335-339, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38093582

RESUMEN

Although endovascular treatment (EVT) has developed and still progressing, calcified lesions remain a big challenge to operators in obtaining good results. Whenever, the eccentric and calcified plaques or nodules are present, balloon dilatation may be difficult and vascular complications may frequently occur. We present a 73-year-old woman, with severe, eccentric, calcified lesion in the right superficial femoral artery (SFA). First, we performed the aggressive wire recanalization in calcified atheroma and dilatation (ARCADIA) technique for the eccentric plaques. Then, we used a WingmanⓇ crossing catheter (ReFlow Medical, Inc.) to penetrate and pass through the calcifications and eventually exchanged to a ParachuteⓇ (Good Care, Inc.) filter wire. Finally, we performed rotational atherectomy using the JETSTREAMⓇ (Boston Scientific) rotational atherectomy device for debulking to obtain good lesion expansion and was able to avoid potential complications. Performing ARCADIA technique then using a Wingman catheter for inserting a filter wire before JETSTREAMⓇ atherectomy is safe and effective for heavily calcified, eccentric lesions. Further studies will be needed to validate the safety and efficacy of this approach.


Asunto(s)
Aterectomía Coronaria , Placa Aterosclerótica , Femenino , Humanos , Anciano , Dilatación , Resultado del Tratamiento , Aterectomía Coronaria/efectos adversos , Aterectomía Coronaria/métodos , Aterectomía/efectos adversos
2.
Angew Chem Int Ed Engl ; : e202408436, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38924653

RESUMEN

Non-directed regioselective activation of diboronic esters, followed by functionalization, is reported. A bulky activator is shown to selectively activate the less hindered boronic ester enabling it to undergo stereospecific cross-coupling to a variety of electrophiles. This steric-based regioselectivity provides a simple and efficient method to prepare highly functionalized, enantiomerically enriched products starting from simple alkenes.

3.
J Nat Prod ; 86(3): 550-556, 2023 03 24.
Artículo en Inglés | MEDLINE | ID: mdl-36897305

RESUMEN

The lichen natural products pulvinamide, rhizocarpic acid, and epanorin have been synthesized and characterized spectroscopically and by X-ray crystallography. The syntheses, by ring-opening of pulvinic acid dilactone (PAD), may well be biomimetic, given the well-known occurrence of PAD in lichen. The enantiomers, ent-rhizocarpic acid and ent-epanorin, and corresponding carboxylic acids, norrhizocarpic acid and norepanorin, were similarly prepared. All compounds were assessed for growth inhibitory activity against selected bacteria, fungi, a protist, a mammalian tumor cell line, and normal cells. Rhizocarpic acid is weakly antibacterial (Bacillus subtilis MIC = 50 µg/mL) and possesses modest but selective antitumor activity (NS-1 murine myeloma MIC = 3.1 µg/mL) with >10-fold potency relative to its enantiomer (MIC = 50 µg/mL).


Asunto(s)
Líquenes , Animales , Ratones , Antibacterianos/química , Bacterias , Hongos , Líquenes/química , Malonatos/metabolismo , Mamíferos , Pruebas de Sensibilidad Microbiana
4.
J Nat Prod ; 86(3): 482-489, 2023 03 24.
Artículo en Inglés | MEDLINE | ID: mdl-36926864

RESUMEN

Two nitrogenous rearranged spongian nor-diterpenoids, dendrillic acids A and B, were isolated from a marine sponge Dendrilla sp. (order: Dendroceratida; family: Darwinellidae). The structures of the metabolites were elucidated on the basis of spectroscopic analysis as well as density functional theory prediction of NMR chemical shifts and application of the DP4+ algorithm. The absolute configuration of the metabolites was established via comparison of experimental and time-dependent density functional theory predicted electronic circular dichroism data. An unusual epimerization reaction was observed leading to the interconversion of the metabolites upon storage in dimethyl sulfoxide solution, which is proposed to proceed via an anionic pathway as probed via isotopic incorporation experiments. Evaluation against a panel of micro-organisms and cell lines revealed that the compounds were devoid of any significant biological activity against all organisms tested, with the exception of mild antiprotozoal activity displayed by dendrillic acid B (2) against Giardia duodenalis.


Asunto(s)
Diterpenos , Poríferos , Animales , Estructura Molecular , Poríferos/química , Espectroscopía de Resonancia Magnética , Diterpenos/química , Línea Celular
5.
BMC Pulm Med ; 23(1): 462, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37993829

RESUMEN

BACKGROUND: Factors predisposing to increased mortality with COVID-19 infection have been identified as male sex, hypertension, obesity, and increasing age. Early studies looking at airway diseases gave some contradictory results. The purpose of our study was to determine global variation in studies in patients hospitalized with COVID-19 in the prevalence of COPD and asthma; and to determine whether the presence of asthma or COPD affected mortality in the same hospital population. METHODS: A systematic review and meta-analysis of the published literature of COPD and asthma as co-morbidities in patients hospitalized with COVID-19 was performed, looking firstly at the prevalence of these diseases in patients hospitalized with COVID-19, and secondly at the relative risk of death from any cause for patients with asthma or COPD. RESULTS: Prevalence of both airway diseases varied markedly by region, making meaningful pooled global estimates of prevalence invalid and not of clinical utility. For individual studies, the interquartile range for asthma prevalence was 4.21 to 12.39%, and for COPD, 3.82 to 11.85%. The relative risk of death with COPD for patients hospitalized with COVID-19 was 1.863 (95% CI 1.640-2.115), while the risk with asthma was 0.918 (95% CI 0.767 to 1.098) with no evidence of increased mortality. CONCLUSIONS: For asthma and COPD, prevalence in patients hospitalized with COVID-19 varies markedly by region. We found no evidence that asthma predisposed to increased mortality in COVID-19 disease. For COPD, there was clear evidence of an association with increased mortality. TRIAL REGISTRATION: The trial was registered with PROSPERO: registration number CRD42021289886.


Asunto(s)
Asma , COVID-19 , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Masculino , COVID-19/epidemiología , COVID-19/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Asma/epidemiología , Asma/complicaciones , Comorbilidad , Prevalencia
6.
Int J Mol Sci ; 24(16)2023 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-37628819

RESUMEN

Most ovarian cancer patients develop recurrent cancers which are often resistant to commonly employed chemotherapy agents, such as cisplatin. We have previously shown that the inhibition of heat shock protein 27 (HSP27) or fatty acid oxidation (FAO) sensitizes cisplatin-resistant ovarian cancer cell lines to cisplatin and dual inhibition of both HSP27 and FAO induces substantial cell death in vitro. However, it is unclear how HSP27 and FAO promote cisplatin resistance, and if dual inhibition of both HSP27 and FAO would augment cisplatin treatment in vivo. Here we showed that HSP27 knockdown in two cisplatin-resistant ovarian cancer cell lines (A2780CIS and PEO4) resulted in more ROS production upon cisplatin treatment. HSP27-knockdown cancer cells exhibited decreased levels of reduced glutathione (GSH) and glucose6phosphate dehydrogenase (G6PD), a crucial pentose phosphate pathway enzyme. ROS depletion with the compound N-acetyl cysteine (NAC) attenuated cisplatin-induced upregulation of HSP27, FAO, and markers of apoptosis and ferroptosis in cisplatin-resistant ovarian cancer cell lines. Finally, inhibition of HSP27 and FAO with ivermectin and perhexiline enhanced the cytotoxic effect of cisplatin in A2780CIS xenograft tumors in vivo. Our results suggest that two different cisplatin-resistant ovarian cancer cell lines upregulate HSP27 and FAO to deplete cisplatin-induced ROS to attenuate cisplatin's cytotoxic effect.


Asunto(s)
Cisplatino , Neoplasias Ováricas , Humanos , Femenino , Cisplatino/farmacología , Proteínas de Choque Térmico HSP27/genética , Especies Reactivas de Oxígeno , Recurrencia Local de Neoplasia , Neoplasias Ováricas/tratamiento farmacológico , Línea Celular , Ácidos Grasos
7.
Glob Chang Biol ; 28(10): 3236-3245, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35239211

RESUMEN

Coastal marshes are globally important, carbon dense ecosystems simultaneously maintained and threatened by sea-level rise. Warming temperatures may increase wetland plant productivity and organic matter accumulation, but temperature-modulated feedbacks between productivity and decomposition make it difficult to assess how wetlands and their thick, organic-rich soils will respond to climate warming. Here, we actively increased aboveground plant-surface and belowground soil temperatures in two marsh plant communities, and found that a moderate amount of warming (1.7°C above ambient temperatures) consistently maximized root growth, marsh elevation gain, and belowground carbon accumulation. Marsh elevation loss observed at higher temperatures was associated with increased carbon mineralization and increased microtopographic heterogeneity, a potential early warning signal of marsh drowning. Maximized elevation and belowground carbon accumulation for moderate warming scenarios uniquely suggest linkages between metabolic theory of individuals and landscape-scale ecosystem resilience and function, but our work indicates nonpermanent benefits as global temperatures continue to rise.


Asunto(s)
Ecosistema , Humedales , Carbono , Humanos , Suelo , Temperatura
8.
Cytotherapy ; 24(6): 619-628, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35314115

RESUMEN

BACKGROUND AIMS: Extracellular vesicles (EVs) are involved in mediating intercellular communication processes. An important goal within the EV field is the study of the biodistribution of EVs and the identification of their target cells. Considering that EV uptake is assumed to be important for EVs in mediating intercellular communication processes, labeling with fluorescent dyes has emerged as a broadly distributed strategy for the identification of EV target cells and tissues. However, the accuracy and specificity of commonly utilized labeling dyes have not been sufficiently analyzed. METHODS: By combining recent advances in imaging flow cytometry for the phenotypic analysis of single EVs and aiming to identify target cells for EVs within therapeutically relevant mesenchymal stromal cell (MSC)-EV preparations, the authors explored the EV labeling efficacy of various fluorescent dyes, specifically carboxyfluorescein diacetate succinimidyl ester, calcein AM, PKH67, BODIPY TR ceramide (Thermo Fisher Scientific, Darmstadt, Germany) and a novel lipid dye called Exoria (Exopharm Limited, Melbourne, Australia). RESULTS: The authors' analyses qualified Exoria as the only dye that specifically labeled EVs within the MSC-EV preparations. Furthermore, the authors demonstrated that Exoria labeling did not interfere with the immunomodulatory properties of the MSC-EV preparations as tested in a multi-donor mixed lymphocyte reaction assay. Within this assay, labeled EVs were differentially taken up by different immune cell types. CONCLUSIONS: Overall, the results qualify Exoria as an appropriate dye for the labeling of EVs derived from the authors' MSC-EV preparations. This study also demonstrates the need for the development of next-generation EV characterization tools that are able to localize and confirm the specificity of EV labeling.


Asunto(s)
Vesículas Extracelulares , Células Madre Mesenquimatosas , Vesículas Extracelulares/metabolismo , Citometría de Flujo , Colorantes Fluorescentes , Distribución Tisular
9.
Pediatr Emerg Care ; 38(1): e354-e359, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33181795

RESUMEN

OBJECTIVES: The aims of the study were to analyze the demographics, presentation, laboratory findings, and complications of pediatric Streptococcus pneumoniae meningitis since the introduction of the 13-valent pneumococcal conjugate vaccine, to improve recognition, and to minimize patient morbidity and mortality. METHODS: This study used a retrospective analysis of pediatric pneumococcal meningitis cases at 2 tertiary healthcare systems in the Southeastern United States from 2010 to 2018. RESULTS: We describe 21 cases of pneumococcal meningitis. All patients presented with fever, 95% had altered mental status by history or examination, and 48% had meningeal signs. Forty-three percent had seen another provider within 48 hours of admission. Forty-eight percent had delay in lumbar puncture (LP) of more than 6 hours after antibiotic administration, decreasing rates of positive cerebrospinal fluid cultures from 100% to 40% (P < 0.001). Decision to delay LP was due to either low suspicion for meningitis (n = 4) or clinical instability (n = 6) and was associated with lower rates of meningeal signs (P = 0.014) and higher rates of altered mental status on examination (P = 0.031). Fourteen patients (67%) were up-to-date on pneumococcal immunization. Serotypes were determined in 16 cases, with 2 patients (13%) immunized against the strain that infected them. Primary outcomes included seizures (48%), hearing loss (48%), cranial nerve palsy (33%), and death (5%). Delay in LP with low suspicion for meningitis was associated with longer hospital length of stay approaching statistical significance (P = 0.053). CONCLUSIONS: Pneumococcal meningitis remains a relevant and potentially fatal disease despite widespread use of 13-valent pneumococcal conjugate vaccine. Its diagnosis is often delayed during interactions with physicians, which may put patients at increased risk for poor clinical outcomes.


Asunto(s)
Meningitis Neumocócica , Infecciones Neumocócicas , Niño , Hospitales Pediátricos , Humanos , Lactante , Meningitis Neumocócica/diagnóstico , Meningitis Neumocócica/epidemiología , Meningitis Neumocócica/prevención & control , Vacunas Neumococicas , Estudios Retrospectivos , Serotipificación , Streptococcus pneumoniae , Vacunas Conjugadas
10.
Mol Ecol ; 30(22): 5658-5673, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34473864

RESUMEN

Periodic and spatially synchronous outbreaks of insect pests have dramatic consequences for boreal and sub-boreal forests. Within these multitrophic systems, parasitoids can be stabilizing agents by dispersing toward patches containing higher host density (the so-called birdfeeder effect). However, we know little about the dispersal abilities of parasitoids in continuous forested landscapes, limiting our understanding of the spatiotemporal dynamics of host-parasitoid systems, and constraining our ability to predict forest resilience in the context of global changes. In this study, we investigate the spatial genetic structure and spatial variation in genetic diversity of two important species of spruce budworm larval parasitoids during outbreaks: Apanteles fumiferanae Viereck (Braconidae) and Glypta fumiferanae (Viereck) (Ichneumonidae). Using parasitoids sampled in 2014 from 26 and 29 locations across a study area of 350,000 km2 , we identified 1,012 and 992 neutral SNP loci for A. fumiferanae (N = 279 individuals) and G. fumiferanae (N = 382), respectively. Using DAPC, PCA, AMOVA, and IBD analyses, we found evidence for panmixia and high genetic connectivity for both species, matching the previously described genetic structure of the spruce budworm within the same context, suggesting similar effective dispersal during outbreaks and high parasitoid population densities between outbreaks. We also found a significant negative relationship between genetic diversity and latitude for A. fumiferanae but not for G. fumiferanae, suggesting that northern range limits may vary by species within the spruce budworm parasitoid community. These spatial dynamics should be considered when predicting future insect outbreak severities in boreal landscapes.


Asunto(s)
Mariposas Nocturnas , Picea , Animales , Bosques , Humanos , Larva/genética , Mariposas Nocturnas/genética , Densidad de Población
11.
Eur J Neurol ; 28(3): 877-883, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33131195

RESUMEN

BACKGROUND AND PURPOSE: ß-Amyloid formation has been suggested to form part of the brain's response to bacterial infection. This hypothesis has been based on experimental animal studies and autopsy studies in humans. We asked if ß-amyloid accumulates locally around a bacterial brain abscess in living human patients. Furthermore, because brain abscess patients may suffer from chronic cognitive symptoms after abscess treatment, we also asked if a brain abscess precipitates accumulation of ß-amyloid in the neocortex in a manner that could explain abscess-related cognitive complaints. METHODS: In a prospective study, we investigated 17 brain abscess patients (age 24-72 years) with 18 F-flutemetamol positron emission tomography on one occasion 1 to 10 months after brain abscess treatment to visualize ß-amyloid accumulation. RESULTS: 18 F-flutemetamol uptake was reduced in the edematous brain tissue that surrounded the abscess remains. On this background of reduced 18 F-flutemetamol signal, three out of 17 patients showed a distinctly increased 18 F-flutemetamol uptake in the tissue immediately surrounding the abscess remains, suggesting accumulation of ß-amyloid. These three patients underwent 18 F-flutemetamol positron emission tomography significantly earlier after neurosurgical treatment (p = 0.042), and they had larger abscesses (p = 0.027) than the rest of the patients. All 17 patients suffered from mental fatigue or some subjective cognitive symptom, such as attention difficulties or memory problems, but in none of the patients was there an increase in neocortical 18 F-flutemetamol signal. CONCLUSIONS: ß-Amyloid may accumulate locally around the abscess remains in some patients with a brain abscess.


Asunto(s)
Enfermedad de Alzheimer , Infecciones Bacterianas , Adulto , Anciano , Péptidos beta-Amiloides/metabolismo , Compuestos de Anilina , Benzotiazoles , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Humanos , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Estudios Prospectivos , Adulto Joven
12.
BMC Pulm Med ; 21(1): 411, 2021 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-34895203

RESUMEN

BACKGROUND: Research questions To compare the efficacy of nintedanib and pirfenidone in the treatment of progressive pulmonary fibrosis; and to compare the efficacy of anti-fibrotic therapy (grouping nintedanib and pirfenidone together) in patients with IPF versus patients with progressive lung fibrosis not classified as IPF. STUDY DESIGN AND METHODS: A search of databases including MEDLINE, EMBASE, PubMed, and clinicaltrials.gov was conducted. Studies were included if they were randomised controlled trials of pirfenidone or nintedanib in adult patients with IPF or non-IPF patients, and with extractable data on mortality or decline in forced vital capacity (FVC). Random effects meta-analyses were performed on changes in FVC and where possible on mortality in the selected studies. RESULTS: 13 trials of antifibrotic therapy were pooled in a meta-analysis (with pirfenidone and nintedanib considered together as anti-fibrotic therapy). The change in FVC was expressed as a standardised difference to allow pooling of percentage and absolute changes. The mean effect size in the IPF studies was - 0.305 (SE 0.043) (p < 0.001) and in the non-IPF studies the figures were - 0.307 (SE 0.063) (p < 0.001). There was no evidence of any difference between the two groups for standardised rate of FVC decline (p = 0.979). Pooling IPF and non-IPF showed a significant reduction in mortality, with mean risk ratio of 07.01 in favour of antifibrotic therapy (p = 0.008). A separate analysis restricted to non-IPF did not show a significant reduction in mortality (risk ratio 0.908 (0.547 to 1.508), p = 0.71. INTERPRETATION: Anti-fibrotic therapy offers protection against the rate of decline in FVC in progressive lung fibrosis, with similar efficacy shown between the two anti-fibrotic agents currently in clinical use. There was no significant difference in efficacy of antifibrotic therapy whether the underlying condition was IPF or non-IPF with progressive fibrosis, supporting the hypothesis of a common pathogenesis. The data in this analysis was insufficient to be confident about a reduction in mortality in non-IPF with anti-fibrotic therapy. Trial Registration PROSPERO, registration number CRD42021266046.


Asunto(s)
Antifibróticos/uso terapéutico , Indoles/uso terapéutico , Fibrosis Pulmonar/tratamiento farmacológico , Piridonas/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Causas de Muerte , Humanos , Fibrosis Pulmonar Idiopática , Fibrosis Pulmonar/mortalidad , Resultado del Tratamiento
13.
Mol Hum Reprod ; 26(8): 636-651, 2020 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-32609359

RESUMEN

Ageing and parturition share common pathways, but their relationship remains poorly understood. Decidual cells undergo ageing as parturition approaches term, and these age-related changes may trigger labour. Mesenchymal stem/stromal cells (MSCs) are the predominant stem cell type in the decidua. Stem cell exhaustion is a hallmark of ageing, and thus ageing of decidual MSCs (DMSCs) may contribute to the functional changes in decidual tissue required for term spontaneous labour. Here, we determine whether DMSCs from patients undergoing spontaneous onset of labour (SOL-DMSCs) show evidence of ageing-related functional changes compared with those from patients not in labour (NIL-DMSCs), undergoing Caesarean section. Placentae were collected from term (37-40 weeks of gestation), SOL (n = 18) and NIL (n = 17) healthy patients. DMSCs were isolated from the decidua basalis that remained attached to the placenta after delivery. DMSCs displayed stem cell-like properties and were of maternal origin. Important cell properties and lipid profiles were assessed and compared between SOL- and NIL-DMSCs. SOL-DMSCs showed reduced proliferation and increased lipid peroxidation, migration, necrosis, mitochondrial apoptosis, IL-6 production and p38 MAPK levels compared with NIL-DMSCs (P < 0.05). SOL- and NIL-DMSCs also showed significant differences in lipid profiles in various phospholipids (phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine), sphingolipids (ceramide, sphingomyelin), triglycerides and acyl carnitine (P < 0.05). Overall, SOL-DMSCs had altered lipid profiles compared with NIL-DMSCs. In conclusion, SOL-DMSCs showed evidence of ageing-related reduced functionality, accumulation of cellular damage and changes in lipid profiles compared with NIL-DMSCs. These changes may be associated with term spontaneous labour.


Asunto(s)
Células Madre Mesenquimatosas/metabolismo , Células del Estroma/metabolismo , Apoptosis/fisiología , Movimiento Celular/fisiología , Decidua/citología , Decidua/metabolismo , Femenino , Humanos , Interleucina-6/metabolismo , Trabajo de Parto , Peroxidación de Lípido/fisiología , Células Madre Mesenquimatosas/citología , Necrosis/metabolismo , Embarazo , Células del Estroma/citología
14.
Proc Natl Acad Sci U S A ; 114(32): 8544-8549, 2017 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-28739903

RESUMEN

Glycoproteins traversing the eukaryotic secretory pathway begin life in the endoplasmic reticulum (ER), where their folding is surveyed by the 170-kDa UDP-glucose:glycoprotein glucosyltransferase (UGGT). The enzyme acts as the single glycoprotein folding quality control checkpoint: it selectively reglucosylates misfolded glycoproteins, promotes their association with ER lectins and associated chaperones, and prevents premature secretion from the ER. UGGT has long resisted structural determination and sequence-based domain boundary prediction. Questions remain on how this single enzyme can flag misfolded glycoproteins of different sizes and shapes for ER retention and how it can span variable distances between the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein. Here, crystal structures of a full-length eukaryotic UGGT reveal four thioredoxin-like (TRXL) domains arranged in a long arc that terminates in two ß-sandwiches tightly clasping the glucosyltransferase domain. The fold of the molecule is topologically complex, with the first ß-sandwich and the fourth TRXL domain being encoded by nonconsecutive stretches of sequence. In addition to the crystal structures, a 15-Å cryo-EM reconstruction reveals interdomain flexibility of the TRXL domains. Double cysteine point mutants that engineer extra interdomain disulfide bridges rigidify the UGGT structure and exhibit impaired activity. The intrinsic flexibility of the TRXL domains of UGGT may therefore endow the enzyme with the promiscuity needed to recognize and reglucosylate its many different substrates and/or enable reglucosylation of N-linked glycans situated at variable distances from the site of misfold.


Asunto(s)
Glucosiltransferasas/química , Glucosiltransferasas/fisiología , Animales , Chaetomium/genética , Chaetomium/metabolismo , Cristalografía por Rayos X/métodos , Retículo Endoplásmico/metabolismo , Eucariontes/metabolismo , Células Eucariotas/metabolismo , Glucosiltransferasas/metabolismo , Glicoproteínas/metabolismo , Conformación Molecular , Dominios Proteicos/fisiología , Pliegue de Proteína , Transporte de Proteínas/fisiología , Especificidad por Sustrato
15.
Genome ; 62(11): 715-727, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31344331

RESUMEN

Identifying adaptive loci is important to understand the evolutionary potential of species undergoing range expansion. However, in expanding populations, spatial demographic processes such as allele surfing can create spatial patterns of neutral genetic variation that appear similar to those generated through adaptive processes. As a result, the false discovery rate of adaptive loci may be inflated in landscape genomic analyses. Here, we take a simulation modelling approach to investigate how range expansion affects our ability to correctly distinguish between neutral and adaptive genetic variation, using the mountain pine beetle outbreak system as a motivating example. We simulated the demographic and population genetic dynamics of populations undergoing range expansion using an individual-based genetic model CDMetaPOP. We investigated how the false discovery rate of adaptive loci is affected by (i) dispersal capacity, (ii) timing of sampling, and (iii) the strength of selection on an adaptive reference locus. We found that a combination of weak dispersal, weak selection, and early sampling presents the greatest risk of misidentifying loci under selection. Expanding populations present unique challenges to the reliable identification of adaptive loci. We demonstrate that there is a need for further methodological development to account for directional demographic processes in landscape genomics.


Asunto(s)
Sitios Genéticos , Genética de Población , Modelos Genéticos , Selección Genética , Algoritmos , Alelos , Animales , Evolución Biológica , Escarabajos/genética , Ecosistema , Variación Genética , Genómica , Pinus , Dinámica Poblacional , Reproducibilidad de los Resultados , Reproducción
16.
Optom Vis Sci ; 96(11): 874-878, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31664013

RESUMEN

SIGNIFICANCE: Obstructive sleep apnea has been linked to the development and progression of diabetic retinopathy. In this study, diabetic patients compliant with continuous positive airway pressure therapy (CPAP) for sleep apnea were less likely to have retinopathy, emphasizing the benefits and potential therapeutic role of CPAP in individuals with both conditions. PURPOSE: The aim of this study was to compare the prevalence of diabetic retinopathy in type 2 diabetic patients with obstructive sleep apnea who were compliant with CPAP therapy with those who were not compliant with CPAP therapy. METHODS: A retrospective cross-sectional review of type 2 diabetic patients using CPAP for obstructive sleep apnea was conducted. The prevalence of retinopathy was identified, and groups with and without retinopathy were compared using univariate analyses and multivariate logistic regression. RESULTS: The prevalence of retinopathy was 19.6% (n = 321). Retinopathy was significantly less prevalent in those compliant with CPAP (odds ratio, 0.54; 95% confidence interval, 0.31 to 0.94; P = .04). The relationship remained statistically significant when adjusting for other factors known to impact the course of diabetic eye disease. CONCLUSIONS: Increased CPAP compliance may mitigate the risk of developing diabetic retinopathy in type 2 diabetic patients with obstructive sleep apnea.


Asunto(s)
Presión de las Vías Aéreas Positiva Contínua , Retinopatía Diabética/prevención & control , Terapia Respiratoria , Apnea Obstructiva del Sueño/terapia , Adulto , Estudios Transversales , Diabetes Mellitus Tipo 2/complicaciones , Progresión de la Enfermedad , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Prevalencia , Estudios Retrospectivos , Estados Unidos , Veteranos
18.
Anal Chem ; 90(3): 1608-1612, 2018 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-29236482

RESUMEN

Aminoethylation of cysteines can provide enzymatically cleavable sites. The ability to obtain peptides containing antibody complementarity determining regions (CDRs) with aminoethylated cysteines was investigated. Because cysteines are often located N-terminal to CDRs, digestion with Lys-N enables acquisition of peptides with CDRs. Lys-N peptides containing an aminoethylated cysteine at the N-terminus were also amidinated. Subsequent collisional activation yields a unique loss of 118 Da that originates from this modified residue, providing a signature ion for cysteine-containing peptides. The relative cleavage efficiencies for Lys-N and trypsin are also compared.


Asunto(s)
Regiones Determinantes de Complementariedad/análisis , Fragmentos de Péptidos/análisis , Rituximab/análisis , Alquilación , Secuencia de Aminoácidos , Cisteína/química , Etilaminas/química , Metaloendopeptidasas/química , Rituximab/química , Análisis de Secuencia de Proteína/métodos
19.
Ecol Appl ; 27(2): 532-544, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27809401

RESUMEN

Detailed understanding of forest disturbance interactions is needed for effective forecasting, modelling, and management. Insect outbreaks are a significant forest disturbance that alters forest structure as well as the distribution and connectivity of combustible fuels at broad spatial scales. The effect of insect outbreaks on fire activity is an important but contentious issue with significant policy consequences. The eastern spruce budworm (Choristoneura fumiferana) is a native defoliating insect in eastern North America whose periodic outbreaks create large patches of dead fir and spruce trees. Of particular concern to fire and forest managers is whether these patches represent an increased fire risk, if so, for how long, and how the relationship between defoliation and fire risk varies through space and time. Previous work suggests a temporary increase in flammability in budworm-killed forests, but regional and seasonal variability in these relationships has not been examined. Using an extensive database on historical lightning-caused fire ignitions and spruce budworm defoliation between 1963 and 2000, we assess the relative importance of cumulative defoliation and fire weather on the probability of ignition in Ontario, Canada. We modeled fire ignition using a generalized additive logistic regression model that accounts for temporal autocorrelation in fire weather. We compared two ecoregions in eastern Ontario (Abitibi Plains) and western Ontario (Lake of the Woods) that differ in terms of climate, geomorphology, and forest composition. We found that defoliation has the potential to both increase and decrease the probability of ignition depending on the time scale, ecoregion, and season examined. Most importantly, we found that lagged spruce budworm defoliation (8-10 yr) increases the risk of fire ignition whereas recent defoliation (1 yr) can decrease this risk. We also found that historical defoliation has a greater influence on ignition risk during the spring than during the summer fire season. Given predicted increases in forest insect activity due to global change, these results represent important information for fire management agencies that can be used to refine existing models of fire risk.


Asunto(s)
Incendios , Bosques , Mariposas Nocturnas/fisiología , Picea/fisiología , Animales , Conservación de los Recursos Naturales , Herbivoria , Modelos Biológicos , Ontario , Dinámica Poblacional
20.
Glob Chang Biol ; 22(1): 404-14, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26342160

RESUMEN

Tidal marshes have a large capacity for producing and storing organic matter, making their role in the global carbon budget disproportionate to land area. Most of the organic matter stored in these systems is in soils where it contributes 2-5 times more to surface accretion than an equal mass of minerals. Soil organic matter (SOM) sequestration is the primary process by which tidal marshes become perched high in the tidal frame, decreasing their vulnerability to accelerated relative sea level rise (RSLR). Plant growth responses to RSLR are well understood and represented in century-scale forecast models of soil surface elevation change. We understand far less about the response of SOM decomposition to accelerated RSLR. Here we quantified the effects of flooding depth and duration on SOM decomposition by exposing planted and unplanted field-based mesocosms to experimentally manipulated relative sea level over two consecutive growing seasons. SOM decomposition was quantified as CO2 efflux, with plant- and SOM-derived CO2 separated via δ(13) CO2 . Despite the dominant paradigm that decomposition rates are inversely related to flooding, SOM decomposition in the absence of plants was not sensitive to flooding depth and duration. The presence of plants had a dramatic effect on SOM decomposition, increasing SOM-derived CO2 flux by up to 267% and 125% (in 2012 and 2013, respectively) compared to unplanted controls in the two growing seasons. Furthermore, plant stimulation of SOM decomposition was strongly and positively related to plant biomass and in particular aboveground biomass. We conclude that SOM decomposition rates are not directly driven by relative sea level and its effect on oxygen diffusion through soil, but indirectly by plant responses to relative sea level. If this result applies more generally to tidal wetlands, it has important implications for models of SOM accumulation and surface elevation change in response to accelerated RSLR.


Asunto(s)
Biomasa , Desarrollo de la Planta , Plantas/metabolismo , Suelo/química , Olas de Marea , Humedales , Dióxido de Carbono/metabolismo , Maryland , Compuestos Orgánicos/metabolismo , Agua de Mar
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