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1.
Cell ; 186(7): 1493-1511.e40, 2023 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-37001506

RESUMEN

Understanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on a single haploid reference genome. Here, we present the EN-TEx resource of 1,635 open-access datasets from four donors (∼30 tissues × âˆ¼15 assays). The datasets are mapped to matched, diploid genomes with long-read phasing and structural variants, instantiating a catalog of >1 million allele-specific loci. These loci exhibit coordinated activity along haplotypes and are less conserved than corresponding, non-allele-specific ones. Surprisingly, a deep-learning transformer model can predict the allele-specific activity based only on local nucleotide-sequence context, highlighting the importance of transcription-factor-binding motifs particularly sensitive to variants. Furthermore, combining EN-TEx with existing genome annotations reveals strong associations between allele-specific and GWAS loci. It also enables models for transferring known eQTLs to difficult-to-profile tissues (e.g., from skin to heart). Overall, EN-TEx provides rich data and generalizable models for more accurate personal functional genomics.


Asunto(s)
Epigenoma , Sitios de Carácter Cuantitativo , Estudio de Asociación del Genoma Completo , Genómica , Fenotipo , Polimorfismo de Nucleótido Simple
2.
Nature ; 610(7933): 699-703, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36261526

RESUMEN

Gas exchange and ion regulation at gills have key roles in the evolution of vertebrates1-4. Gills are hypothesized to have first acquired these important homeostatic functions from the skin in stem vertebrates, facilitating the evolution of larger, more-active modes of life2,3,5. However, this hypothesis lacks functional support in relevant taxa. Here we characterize the function of gills and skin in a vertebrate (lamprey ammocoete; Entosphenus tridentatus), a cephalochordate (amphioxus; Branchiostoma floridae) and a hemichordate (acorn worm; Saccoglossus kowalevskii) with the presumed burrowing, filter-feeding traits of vertebrate ancestors6-9. We provide functional support for a vertebrate origin of gas exchange at the gills with increasing body size and activity, as direct measurements in vivo reveal that gills are the dominant site of gas exchange only in ammocoetes, and only with increasing body size or challenges to oxygen supply and demand. Conversely, gills of all three taxa are implicated in ion regulation. Ammocoete gills are responsible for all ion flux at all body sizes, whereas molecular markers for ion regulation are higher in the gills than in the skin of amphioxus and acorn worms. This suggests that ion regulation at gills has an earlier origin than gas exchange that is unrelated to vertebrate size and activity-perhaps at the very inception of pharyngeal pores in stem deuterostomes.


Asunto(s)
Branquias , Iones , Oxígeno , Filogenia , Vertebrados , Animales , Branquias/metabolismo , Anfioxos/metabolismo , Oxígeno/metabolismo , Vertebrados/clasificación , Vertebrados/metabolismo , Iones/metabolismo , Tamaño Corporal , Lampreas/metabolismo , Piel/metabolismo
3.
J Gastroenterol Hepatol ; 39(3): 464-472, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38054398

RESUMEN

BACKGROUND AND AIM: Flexible sigmoidoscopy (FS) without analgesia or sedation can be unpleasant for patients, resulting in unsatisfactory examinations. Prior familiarization videos (FVs) and intra-procedural Entonox inhalation have shown inconsistent effects. This study investigated their effects on undesirable participant factors (anxiety, stress, discomfort, pain, satisfaction, later unpleasant recall of procedure, and vasovagal reactions) and clinical effectiveness (extent of bowel seen, lesions detected, and procedural/recovery times). METHODS: This cluster-randomized single-center study evaluated 138 participants undergoing FS. There were 46 controls, 49 given access to FV, and 43 access to both FV and self-administered Entonox. Participant factors were measured by self-administered questionnaires, independent nurse assessments, and heart rate variability (HRV) metrics. RESULTS: Questionnaires showed that the FV group was slightly more tense and upset before FS, but knowledge of Entonox availability reduced anxiety. Nonlinear HRV metrics confirmed reduced intra-procedural stress response in the FV/Entonox group compared with controls and FV alone (P < 0.05). Entonox availability allowed more bowel to be examined (P < 0.001) but increased procedure time (P < 0.05), while FV alone had no effect. FV/Entonox participants reported 1 month after FS less discomfort during the procedure. Other comparisons showed no significant differences between treatment groups, although one HRV metric showed some potential to predict vasovagal reactions. CONCLUSIONS: Entonox availability significantly improved clinical effectiveness and caused a slight reduction in undesirable participant factors. The FV alone did not reduce undesirable participant factors or improve clinical effectiveness. Nonlinear HRV metrics recorded effects in agreement with stress reduction and may be useful for prediction of vasovagal events in future studies.


Asunto(s)
Óxido Nitroso , Oxígeno , Sigmoidoscopía , Humanos , Analgesia , Dolor/etiología , Sigmoidoscopía/efectos adversos , Resultado del Tratamiento
4.
Genome Res ; 30(7): 1060-1072, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32718982

RESUMEN

Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-to-date lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.


Asunto(s)
ARN Largo no Codificante/fisiología , Procesos de Crecimiento Celular/genética , Movimiento Celular/genética , Fibroblastos/citología , Fibroblastos/metabolismo , Humanos , Canales de Potasio KCNQ/metabolismo , Anotación de Secuencia Molecular , Oligonucleótidos Antisentido , ARN Largo no Codificante/antagonistas & inhibidores , ARN Largo no Codificante/metabolismo , ARN Interferente Pequeño
5.
J Biol Chem ; 297(2): 100937, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34224731

RESUMEN

The endoplasmic reticulum (ER) is a membrane-bound organelle responsible for protein folding, lipid synthesis, and calcium homeostasis. Maintenance of ER structural integrity is crucial for proper function, but much remains to be learned about the molecular players involved. To identify proteins that support the structure of the ER, we performed a proteomic screen and identified nodal modulator (NOMO), a widely conserved type I transmembrane protein of unknown function, with three nearly identical orthologs specified in the human genome. We found that overexpression of NOMO1 imposes a sheet morphology on the ER, whereas depletion of NOMO1 and its orthologs causes a collapse of ER morphology concomitant with the formation of membrane-delineated holes in the ER network positive for the lysosomal marker lysosomal-associated protein 1. In addition, the levels of key players of autophagy including microtubule-associated protein light chain 3 and autophagy cargo receptor p62/sequestosome 1 strongly increase upon NOMO depletion. In vitro reconstitution of NOMO1 revealed a "beads on a string" structure likely representing consecutive immunoglobulin-like domains. Extending NOMO1 by insertion of additional immunoglobulin folds results in a correlative increase in the ER intermembrane distance. Based on these observations and a genetic epistasis analysis including the known ER-shaping proteins Atlastin2 and Climp63, we propose a role for NOMO1 in the functional network of ER-shaping proteins.


Asunto(s)
Retículo Endoplásmico , Proteómica , Proteína Sequestosoma-1 , Autofagia , Estrés del Retículo Endoplásmico , Homeostasis , Humanos , Lisosomas/metabolismo
6.
Proc Biol Sci ; 289(1974): 20220258, 2022 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-35538784

RESUMEN

Deuterostomes comprise three phyla with radically different body plans. Phylogenetic bracketing of the living deuterostome clades suggests the latest common ancestor of echinoderms, hemichordates and chordates was a bilaterally symmetrical worm with pharyngeal openings, with these characters lost in echinoderms. Early fossil echinoderms with pharyngeal openings have been described, but their interpretation is highly controversial. Here, we critically evaluate the evidence for pharyngeal structures (gill bars) in the extinct stylophoran echinoderms Lagynocystis pyramidalis and Jaekelocarpus oklahomensis using virtual models based on high-resolution X-ray tomography scans of three-dimensionally preserved fossil specimens. Multivariate analyses of the size, spacing and arrangement of the internal bars in these fossils indicate they are substantially more similar to gill bars in modern enteropneust hemichordates and cephalochordates than to other internal bar-like structures in fossil blastozoan echinoderms. The close similarity between the internal bars of the stylophorans L. pyramidalis and J. oklahomensis and the gill bars of extant chordates and hemichordates is strong evidence for their homology. Differences between these internal bars and bar-like elements of the respiratory systems in blastozoans suggest these structures might have arisen through parallel evolution across deuterostomes, perhaps underpinned by a common developmental genetic mechanism.


Asunto(s)
Cordados no Vertebrados , Cordados , Animales , Evolución Biológica , Cordados no Vertebrados/genética , Equinodermos , Fósiles , Branquias , Filogenia
7.
J Exp Biol ; 225(8)2022 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-35389496

RESUMEN

Crustacean filter feeders capture oil droplets with the use of their ramified appendages. These appendages behave as paddles or sieves, based on the system's Reynolds number. Here, we used high-speed videography, scanning electron microscopy and fluid mechanics to study the capturing mechanisms of crude oil droplets and the filtering appendage's wettability by two species of barnacles (Balanus glandula and Balanus crenatus) and of the freshwater cladoceran Daphnia magna. Our results show that barnacle appendages behave as paddles and capture droplets in their boundary layers at low Reynolds number. At high Reynolds number, droplets are most likely to be captured via direct interception. There is an intermediate range of Reynolds number where droplets can be captured by both mechanisms at the same time. Daphnia magna captures droplets in the boundary layers of the third and fourth pair of thoracic legs with a metachronal motion of the appendages. All studied surfaces were revealed to be highly lipophobic, demonstrating captured oil droplets with high contact angles. We also discuss implications of such capture mechanisms and wettability on potential ingestion of crude oil by filter feeders. These results further our understanding of the capture of crude oil by filter feeders, shedding light on the main entry point of oil in marine food webs.


Asunto(s)
Contaminación por Petróleo , Petróleo , Thoracica , Animales , Daphnia , Cadena Alimentaria
8.
Nature ; 527(7579): 459-65, 2015 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-26580012

RESUMEN

Acorn worms, also known as enteropneust (literally, 'gut-breathing') hemichordates, are marine invertebrates that share features with echinoderms and chordates. Together, these three phyla comprise the deuterostomes. Here we report the draft genome sequences of two acorn worms, Saccoglossus kowalevskii and Ptychodera flava. By comparing them with diverse bilaterian genomes, we identify shared traits that were probably inherited from the last common deuterostome ancestor, and then explore evolutionary trajectories leading from this ancestor to hemichordates, echinoderms and chordates. The hemichordate genomes exhibit extensive conserved synteny with amphioxus and other bilaterians, and deeply conserved non-coding sequences that are candidates for conserved gene-regulatory elements. Notably, hemichordates possess a deuterostome-specific genomic cluster of four ordered transcription factor genes, the expression of which is associated with the development of pharyngeal 'gill' slits, the foremost morphological innovation of early deuterostomes, and is probably central to their filter-feeding lifestyle. Comparative analysis reveals numerous deuterostome-specific gene novelties, including genes found in deuterostomes and marine microbes, but not other animals. The putative functions of these genes can be linked to physiological, metabolic and developmental specializations of the filter-feeding ancestor.


Asunto(s)
Cordados no Vertebrados/genética , Evolución Molecular , Genoma/genética , Animales , Cordados no Vertebrados/clasificación , Secuencia Conservada/genética , Equinodermos/clasificación , Equinodermos/genética , Familia de Multigenes/genética , Filogenia , Transducción de Señal , Sintenía/genética , Factor de Crecimiento Transformador beta
9.
BMC Genomics ; 20(1): 162, 2019 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-30819105

RESUMEN

BACKGROUND: Understanding how transcription occurs requires the integration of genome-wide and locus-specific information gleaned from robust technologies. Chromatin immunoprecipitation (ChIP) is a staple in gene expression studies, and while genome-wide methods are available, high-throughput approaches to analyze defined regions are lacking. RESULTS: Here, we present carbon copy-ChIP (2C-ChIP), a versatile, inexpensive, and high-throughput technique to quantitatively measure the abundance of DNA sequences in ChIP samples. This method combines ChIP with ligation-mediated amplification (LMA) and deep sequencing to probe large genomic regions of interest. 2C-ChIP recapitulates results from benchmark ChIP approaches. We applied 2C-ChIP to the HOXA cluster to find that a region where H3K27me3 and SUZ12 linger encodes HOXA-AS2, a long non-coding RNA that enhances gene expression during cellular differentiation. CONCLUSIONS: 2C-ChIP fills the need for a robust molecular biology tool designed to probe dedicated genomic regions in a high-throughput setting. The flexible nature of the 2C-ChIP approach allows rapid changes in experimental design at relatively low cost, making it a highly efficient method for chromatin analysis.


Asunto(s)
Inmunoprecipitación de Cromatina/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Análisis de Secuencia de ADN , Diferenciación Celular/genética , Células Cultivadas , Epigénesis Genética , Expresión Génica , Genes Homeobox , Genómica , Humanos , ARN Largo no Codificante/fisiología , Reacción en Cadena en Tiempo Real de la Polimerasa
10.
Nature ; 495(7442): 503-6, 2013 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-23485974

RESUMEN

Hemichordates are a marine group that, apart from one monospecific pelagic larval form, are represented by the vermiform enteropneusts and minute colonial tube-dwelling pterobranchs. Together with echinoderms, they comprise the clade Ambulacraria. Despite their restricted diversity, hemichordates provide important insights into early deuterostome evolution, notably because of their pharyngeal gill slits. Hemichordate phylogeny has long remained problematic, not least because the nature of any transitional form that might serve to link the anatomically disparate enteropneusts and pterobranchs is conjectural. Hence, inter-relationships have also remained controversial. For example, pterobranchs have sometimes been compared to ancestral echinoderms. Molecular data identify enteropneusts as paraphyletic, and harrimaniids as the sister group of pterobranchs. Recent molecular phylogenies suggest that enteropneusts are probably basal within hemichordates, contrary to previous views, but otherwise provide little guidance as to the nature of the primitive hemichordate. In addition, the hemichordate fossil record is almost entirely restricted to peridermal skeletons of pterobranchs, notably graptolites. Owing to their low preservational potentials, fossil enteropneusts are exceedingly rare, and throw no light on either hemichordate phylogeny or the proposed harrimaniid-pterobranch transition. Here we describe an enteropneust, Spartobranchus tenuis (Walcott, 1911), from the Middle Cambrian-period (Series 3, Stage 5) Burgess Shale. It is remarkably similar to the extant harrimaniids, but differs from all known enteropneusts in that it is associated with a fibrous tube that is sometimes branched. We suggest that this is the precursor of the pterobranch periderm, and supports the hypothesis that pterobranchs are miniaturized and derived from an enteropneust-like worm. It also shows that the periderm was acquired before size reduction and acquisition of feeding tentacles, and that coloniality emerged through aggregation of individuals, perhaps similar to the Cambrian rhabdopleurid Fasciculitubus. The presence of both enteropneusts and pterobranchs in Middle Cambrian strata, suggests that hemichordates originated at the onset of the Cambrian explosion.


Asunto(s)
Cordados no Vertebrados , Fósiles , Filogenia , Animales , Colombia Británica , Cordados no Vertebrados/anatomía & histología , Cordados no Vertebrados/clasificación , Equinodermos/anatomía & histología , Equinodermos/clasificación
11.
Inorg Chem ; 57(9): 4959-4965, 2018 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-29648455

RESUMEN

The uptake of gaseous iodine into the crystalline sponge material [(ZnI2)3(tpt)2]·0.7triphenylene·0.3PhNO2·0.7C6H12 1 (tpt = 2,4,6-tris(4-pyridyl)-1,3,5-triazine) has been monitored by dynamic X-ray diffraction and thermogravimetric analysis. The X-ray analyses have enabled the location, quantity, uptake rate, and subsequent chemistry of the iodine upon inclusion into the pores to be determined. An uptake of 6.0 wt % (0.43 I2 per formula unit) was observed crystallographically over a period of 90 min before crystal degradation occurred. The included iodine molecules interact with the iodine atoms of the ZnI2 nodes at three different sites, forming coordinated I3- ions. The results contrast to recent observations on [(ZnI2)3(tpt)2] without the triphenylene guests which show the presence of I42- ions with low quantities of absorbed iodine.

12.
BMC Biol ; 14: 56, 2016 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-27383414

RESUMEN

BACKGROUND: The combination of a meager fossil record of vermiform enteropneusts and their disparity with the tubicolous pterobranchs renders early hemichordate evolution conjectural. The middle Cambrian Oesia disjuncta from the Burgess Shale has been compared to annelids, tunicates and chaetognaths, but on the basis of abundant new material is now identified as a primitive hemichordate. RESULTS: Notable features include a facultative tubicolous habit, a posterior grasping structure and an extensive pharynx. These characters, along with the spirally arranged openings in the associated organic tube (previously assigned to the green alga Margaretia), confirm Oesia as a tiered suspension feeder. CONCLUSIONS: Increasing predation pressure was probably one of the main causes of a transition to the infauna. In crown group enteropneusts this was accompanied by a loss of the tube and reduction in gill bars, with a corresponding shift to deposit feeding. The posterior grasping structure may represent an ancestral precursor to the pterobranch stolon, so facilitating their colonial lifestyle. The focus on suspension feeding as a primary mode of life amongst the basal hemichordates adds further evidence to the hypothesis that suspension feeding is the ancestral state for the major clade Deuterostomia.


Asunto(s)
Cordados no Vertebrados/clasificación , Fósiles , Animales , Evolución Biológica , Cordados no Vertebrados/anatomía & histología , Branquias/anatomía & histología , Filogenia
13.
Value Health ; 19(5): 661-9, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27565284

RESUMEN

OBJECTIVES: To investigate heterogeneity of treatment effect (HTE) for anticoagulants in atrial fibrillation across subgroups defined by 1) clinical characteristics and 2) variation in patient utilities for benefits and harms of treatment. METHODS: We reanalyzed aggregate data from a published network meta-analysis that compared four anticoagulants for atrial fibrillation (apixaban, dabigatran, edoxaban, and rivaroxaban) as well as warfarin. Event rates for stroke/systemic embolism (SE) and major bleeding were generated for each agent across seven subgroups, and rankings were developed on the basis of clinical performance. Utilities were derived from a national catalog and then applied to generate summary measures of benefit. The choice between any two agents was examined across a range of plausible utility values, defined as the interquartile range for stroke/SE and major bleeding. RESULTS: Little HTE was apparent in clinical and utility-adjusted analyses. Dabigatran 150 mg produced the lowest rates of stroke/SE, and edoxaban 30 mg had the lowest rate of major bleeding. Greater HTE was observed when utilities were varied across a plausible utility range. For example, among patients 75 years and older, dabigatran 150 mg would be preferred over edoxaban 30 mg when mean utility estimates are used. The preferred agent, however, would change at plausible utility thresholds of 0.6 and 0.7 for major bleeding and stroke/SE, respectively. Nearly 25% of all possible comparisons would see a change in preferred treatment within the plausible utility range. CONCLUSIONS: The optimal choice of anticoagulant in atrial fibrillation differs across subgroups defined by clinical characteristics and reasonable ranges of utilities.


Asunto(s)
Administración Oral , Anticoagulantes/administración & dosificación , Fibrilación Atrial/tratamiento farmacológico , Anciano , Femenino , Estado de Salud , Humanos , Masculino , Prioridad del Paciente , Calidad de Vida , Resultado del Tratamiento , Warfarina/administración & dosificación
14.
Can J Surg ; 59(4): 268-75, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27454839

RESUMEN

BACKGROUND: Following a landmark study showing decreased morbidity and mortality after implementation of the surgical safety checklist (SSC), it has been widely adopted into perioperative policy. We explored the impact of attitudes and beliefs surrounding the SSC on its uptake in Calgary. METHODS: We used qualitative methodology to examine factors influencing SSC use. We performed semistructured interviews based on Rogers' theory of diffusion of innovation. Purposive and snowball sampling were used to identify surgeons, anesthesiologists and operating room nurses from hospitals in Calgary. Data collection and analysis were based on grounded theory. Two individuals jointly analyzed data and achieved consensus on emerging themes. RESULTS: Generated themes included 1) the SSC has brought organization to previous informal perioperative checks, 2) the SSC is most helpful when it is simple, and 3) the 3 current components of the checklist are redundant. The briefing was considered the most important aspect and the debriefing the least important. Initially the SSC was difficult to implement owing to a shift in time management and perioperative culture; however, it has now assimilated into perioperative routine. Finally, though most participants agreed that the SSC might avoid some delays and complications, only a few believe there have been observable improvements to morbidity and mortality. CONCLUSION: Although the SSC has been integrated into perioperative practice in Calgary, participants believe that previous informal checkpoints were able to circumvent most perioperative issues. Although the SSC may help with flow and equipment, participants believe it fails to show a subjective, clinically important improvement.


BACKGROUND: Après une étude charnière ayant montré une baisse de la morbidité et de la mortalité après la mise en oeuvre de la liste de contrôle de la sécurité chirurgicale, cette dernière a été largement intégrée aux politiques périopératoires. Nous avons examiné l'effet des attitudes et des croyances entourant la liste sur son adoption à Calgary. METHODS: À l'aide d'une méthode qualitative, nous nous sommes penchés sur les facteurs influençant l'utilisation de la liste. Pour ce faire, nous avons effectué des entrevues semi-dirigées fondées sur la théorie de la diffusion de l'innovation de Rogers. Nous avons utilisé l'échantillonnage dirigé et le sondage en boule de neige pour cibler des chirurgiens, des anesthésiologistes et des membres du personnel infirmier de salle d'opération des hôpitaux de Calgary. La collecte et l'analyse des données étaient fondées sur la théorie ancrée. Deux personnes ont analysé ensemble les données et se sont entendues sur les thèmes émergents. RESULTS: Voici les principales conclusions dégagées : 1) la liste a permis de structurer les contrôles périopératoires non officiels du passé, 2) la liste est surtout utile quand elle est simple et 3) les 3 composantes actuelles de la liste de contrôle sont redondantes. Le breffage était considéré comme étant l'aspect le plus important et le débreffage, le moins important. Au départ, la liste a été difficile à mettre en oeuvre en raison des changements à apporter à la gestion du temps et à la culture périopératoire; cependant, elle est maintenant bien intégrée dans la routine périopératoire. Enfin, bien que la plupart des participants conviennent que la liste peut éviter des retards et des complications, seuls quelques-uns croient qu'il y a eu une amélioration observable de la morbidité et de la mortalité. CONCLUSION: Si la liste de contrôle de la sécurité chirurgicale a été intégrée dans la pratique périopératoire à Calgary, les participants croient que les points de contrôle non officiels du passé pouvaient prévenir la plupart des problèmes périopératoires. La liste est utile pour ce qui est du processus et de l'équipement, mais les participants croient qu'elle n'apporte pas d'amélioration subjective importante d'un point de vue clinique.


Asunto(s)
Lista de Verificación/normas , Atención Perioperativa/normas , Mejoramiento de la Calidad/normas , Procedimientos Quirúrgicos Operativos/normas , Alberta , Investigación sobre Servicios de Salud , Humanos , Investigación Cualitativa
15.
Proc Biol Sci ; 281(1786)2014 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-24850925

RESUMEN

While some aspects of the phylogeny of the five living echinoderm classes are clear, the position of the ophiuroids (brittlestars) relative to asteroids (starfish), echinoids (sea urchins) and holothurians (sea cucumbers) is controversial. Ophiuroids have a pluteus-type larva in common with echinoids giving some support to an ophiuroid/echinoid/holothurian clade named Cryptosyringida. Most molecular phylogenetic studies, however, support an ophiuroid/asteroid clade (Asterozoa) implying either convergent evolution of the pluteus or reversals to an auricularia-type larva in asteroids and holothurians. A recent study of 10 genes from four of the five echinoderm classes used 'phylogenetic signal dissection' to separate alignment positions into subsets of (i) suboptimal, heterogeneously evolving sites (invariant plus rapidly changing) and (ii) the remaining optimal, homogeneously evolving sites. Along with most previous molecular phylogenetic studies, their set of heterogeneous sites, expected to be more prone to systematic error, support Asterozoa. The homogeneous sites, in contrast, support an ophiuroid/echinoid grouping, consistent with the cryptosyringid clade, leading them to posit homology of the ophiopluteus and echinopluteus. Our new dataset comprises 219 genes from all echinoderm classes; analyses using probabilistic Bayesian phylogenetic methods strongly support Asterozoa. The most reliable, slowly evolving quartile of genes also gives highest support for Asterozoa; this support diminishes in second and third quartiles and the fastest changing quartile places the ophiuroids close to the root. Using phylogenetic signal dissection, we find heterogenous sites support an unlikely grouping of Ophiuroidea + Holothuria while homogeneous sites again strongly support Asterozoa. Our large and taxonomically complete dataset finds no support for the cryptosyringid hypothesis; in showing strong support for the Asterozoa, our preferred topology leaves the question of homology of pluteus larvae open.


Asunto(s)
Equinodermos/clasificación , Equinodermos/genética , Genoma , Filogenia , Animales , Evolución Biológica , Equinodermos/crecimiento & desarrollo , Evolución Molecular , Larva/genética , Larva/crecimiento & desarrollo , Datos de Secuencia Molecular , Análisis de Secuencia de Proteína
16.
BMC Cancer ; 14: 471, 2014 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-24972449

RESUMEN

BACKGROUND: Advanced pancreatic cancer confers poor prognosis and treatment advancement has been slow. Recent randomized clinical trials (RCTs) have demonstrated survival benefits for combination therapy compared to gemcitabine alone. However, the comparative benefits and harms of available combination chemotherapy treatments are not clear. We therefore conducted a systematic review and Bayesian network meta-analysis to assess the comparative safety and efficacy of chemotherapy regimens for the treatment of advanced pancreatic cancer. METHODS: MEDLINE, PubMed, EMBASE, Cochrane Central Registry of Clinical trials and abstracts from major scientific meetings were searched for RCTs published from 2002 to 2013. Key outcomes were overall survival (OS), progression free survival (PFS), and safety including grade 3-4 febrile neutropenia, neutropenia, vomiting, diarrhea, fatigue and sensory neuropathy. Bayesian network meta-analyses were conducted to calculate survival and safety outcomes using gemcitabine (GEM) as the reference comparator. Effect estimates and 95% credible intervals were calculated for each comparison. Mean ranks and the probability of being best were obtained for each treatment analyzed in the network meta-analysis. RESULTS: The search identified 23 studies involving 19 different treatment regimens and 9,989 patients. FOLFIRINOX, GEM/cisplatin/epirubicin/5FU (PEFG), GEM/NAB-paclitaxel (NAB-P), GEM/erlotinib+/-bevacizumab, GEM/capecitabine, and GEM/oxaliplatin were associated with statistically significant improvements in OS and PFS relative to gemcitabine alone and several other treatments. They were amongst the top ranked for survival outcomes amongst other treatments included. No significant differences were found for other combination chemotherapy treatments. Effect estimates from indirect comparisons matched closely to estimates derived from pairwise comparisons. Overall, combination therapies had greater risk for evaluated grade 3-4 toxicities over gemcitabine alone. CONCLUSIONS: In the absence of head-to-head comparisons, we performed a mixed-treatment analysis to achieve high-quality information on the effectiveness and safety of each treatment. This study suggests that some combination therapies may offer greater benefits in the treatment of advanced pancreatic cancer than others. To more fully elucidate the comparative benefits and harms of different combination chemotherapy regimens, rigorously conducted comparative studies, or network meta-analysis of patient-level data are required.


Asunto(s)
Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Teorema de Bayes , Bases de Datos como Asunto , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis de Supervivencia , Resultado del Tratamiento
17.
Zootaxa ; 3630: 143-54, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-26131502

RESUMEN

Twenty three enteropneust species have been described from the west coast of North America, including one species from the family Ptychoderidae; Glossobalanus berkeleyi from the Salish Sea, Vancouver Island. Here we use morphology to describe three additional species of acorn worms in the genus Glossobalanus: G. williami from Cape Arago, Oregon; G hartmanae and G. barnharti from La Jolla, California. Notes on the habit and localization of each species as well as a dichotomous key to the genera of the family Ptychoderidae are provided.


Asunto(s)
Eucariontes/clasificación , Distribución Animal , Estructuras Animales/anatomía & histología , Animales , América del Norte
18.
Mar Pollut Bull ; 193: 115174, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37336047

RESUMEN

Various methods of oil spill remediation exist, e.g., floating booms, controlled burning and the release of chemical surfactants. These surfactants facilitate the breakup of the slick into micron-sized droplets. Here, we studied the impact such a surfactant has on the size distribution of oil droplets in the water column and in the gut of the filter feeder Daphnia magna. We also studied the effect of surfactants on detachment conditions of chemically and mechanically dispersed oil (respectively MDO and CDO) droplets from capture fibers. Our results show that including solubilized dioctyl sulfosuccinate sodium salt in the mixing of the emulsion produces smaller droplets and a narrower size distribution in the water. In the gut, the size of ingested droplets does not change whether the oil is mixed mechanically or chemically. Also, surfactant coated droplets detach at a lower velocity than mechanically dispersed droplet because of their lower oil/water interfacial tension.


Asunto(s)
Contaminación por Petróleo , Petróleo , Tensoactivos , Ácido Dioctil Sulfosuccínico , Emulsiones , Petróleo/análisis
19.
Front Bioinform ; 3: 1285828, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38455089

RESUMEN

Hi-C is one of the most widely used approaches to study three-dimensional genome conformations. Contacts captured by a Hi-C experiment are represented in a contact frequency matrix. Due to the limited sequencing depth and other factors, Hi-C contact frequency matrices are only approximations of the true interaction frequencies and are further reported without any quantification of uncertainty. Hence, downstream analyses based on Hi-C contact maps (e.g., TAD and loop annotation) are themselves point estimations. Here, we present the Hi-C interaction frequency sampler (HiCSampler) that reliably infers the posterior distribution of the interaction frequency for a given Hi-C contact map by exploiting dependencies between neighboring loci. Posterior predictive checks demonstrate that HiCSampler can infer highly predictive chromosomal interaction frequency. Summary statistics calculated by HiCSampler provide a measurement of the uncertainty for Hi-C experiments, and samples inferred by HiCSampler are ready for use by most downstream analysis tools off the shelf and permit uncertainty measurements in these analyses without modifications.

20.
Evodevo ; 14(1): 6, 2023 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-37076909

RESUMEN

Schizocardium karankawa sp. nov. has been collected from subtidal muds of the Laguna Madre, Texas, and the Mississippi coast, Gulf of Mexico. The Texas population is reproductive from early February to mid-April. Gametes are liberated by a small incision in a gonad. Oocyte germinal vesicle breakdown is increased in the presence of sperm, and the highest fertilization success was in the artificial seawater Jamarin U. Manually dechorionated embryos develop normally. Development was asynchronous via a tornaria larva, metamorphosis and maintained to the juvenile worm 6 gill-pore stage. Phalloidin-labeled late-stage tornaria revealed retractor muscles that connect the pericardial sac with the apical tuft anteriorly, the oesophagus ventrally, and muscle cells of the early mesocoels. The muscle development of early juvenile worms began with dorso-lateral trunk muscles, lateral trunk bands, and sphincters around the gill pores and anus. Adult worms are characterized by a stomochord that bifurcates anteriorly into paired vermiform processes, gill bars that extend almost the entire dorsal to ventral branchial region resulting in a narrow ventral hypobranchial ridge, and an elaborate epibranchial organ with six zones of discrete cell types. The trunk has up to three rows of liver sacs, and lateral gonads. The acorn worm evo-devo model species Saccoglossus kowalevskii, Ptychodera flava, and Schizocardium californicum are phylogenetically distant with disparate life histories. S. karnakawa from S. californicum are phylogenetically close, and differences between them that become apparent as adult worms include the number of gill pores and hepatic sacs, and elaborations of the heart-kidney-stomochord complex. An important challenge for evolutionary developmental biology is to form links from phylogenetically distant and large-scale differences to phylogenetically close and small-scale differences. This description of the embryology, development, and adult morphology of S. karankawa permits investigations into how acorn worm development evolves at fine scales.

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