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KEY MESSAGE: Comparing populations derived, respectively, from polyploid Sorghum halepense and its progenitors improved knowledge of plant architecture and showed that S. halepense harbors genetic novelty of potential value for sorghum improvement Vegetative growth and the timing of the vegetative-to-reproductive transition are critical to a plant's fitness, directly and indirectly determining when and how a plant lives, grows and reproduces. We describe quantitative trait analysis of plant height and flowering time in the naturally occurring tetraploid Sorghum halepense, using two novel BC1F2 populations totaling 246 genotypes derived from backcrossing two tetraploid Sorghum bicolor x S. halepense F1 plants to a tetraploidized S. bicolor. Phenotyping for two years each in Bogart, GA and Salina, KS allowed us to dissect variance into narrow-sense genetic (QTLs) and environmental components. In crosses with a common S. bicolor BTx623 parent, comparison of QTLs in S. halepense, its rhizomatous progenitor S. propinquum and S. bicolor race guinea which is highly divergent from BTx623 permit inferences of loci at which new alleles have been associated with improvement of elite sorghums. The relative abundance of QTLs unique to the S. halepense populations may reflect its polyploidy and subsequent 'diploidization' processes often associated with the formation of genetic novelty, a possibility further supported by a high level of QTL polymorphism within sibling lines derived from a common S. halepense parent. An intriguing hypothesis for further investigation is that polyploidy of S. halepense following 96 million years of abstinence, coupled with natural selection during its spread to diverse environments across six continents, may provide a rich collection of novel alleles that offer potential opportunities for sorghum improvement.
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Mapeamento Cromossômico/métodos , Cromossomos de Plantas/genética , Locos de Características Quantitativas , Sorghum/classificação , Sorghum/genética , Cruzamentos Genéticos , FenótipoRESUMO
In this paper, we extend the use of assurance for a single study to explore how meeting a study's pre-defined success criteria could update our beliefs about the true treatment effect and impact the assurance of subsequent studies. This concept of conditional assurance, the assurance of a subsequent study conditional on success in an initial study, can be used assess the de-risking potential of the study requiring immediate investment, to ensure it provides value within the overall development plan. If the planned study does not discharge sufficient later phase risk, alternative designs and/or success criteria should be explored. By transparently laying out the different design options and the risks associated, this allows for decision makers to make quantitative investment choices based on their risk tolerance levels and potential return on investment. This paper lays out the derivation of conditional assurance, discusses how changing the design of a planned study will impact the conditional assurance of a future study, as well as presenting a simple illustrative example of how this methodology could be used to transparently compare development plans to aid decision making within an organisation.
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Desenvolvimento de MedicamentosRESUMO
Phosphoinositide 3-kinase δ (PI3Kδ) is a lipid kinase involved in leukocyte recruitment and activation. Activation of PI3Kδ has been linked to airway inflammation and asthma pathogenesis. This randomized, double-blind, placebo-controlled, crossover study investigated the efficacy, safety, tolerability, and pharmacokinetics of a PI3Kδ inhibitor, nemiralisib (GSK2269557), in patients with persistent, uncontrolled asthma. Patients (n = 50) received once-daily inhaled nemiralisib (1000 µg) or placebo for 28 days, with a crossover to the alternative treatment following a 4-week washout period. Spirometry demonstrated no discernible difference in trough forced expiratory volume in 1 second (FEV1) from baseline (adjusted posterior median 7 ml; 95% credible interval -83, 102 ml) between nemiralisib and placebo treatment at day 28 (primary endpoint). These results were supported by most secondary endpoints, including weighted mean FEV1 (0-4 hours) and change in trough forced vital capacity at day 28. Nemiralisib was generally well-tolerated, with few side effects except for post-inhalation cough (nemiralisib: 35%; placebo: 9%). At day 14, sputum interleukin (IL)-5, IL-13, IL-6, and IL-8 levels were reduced by a median of 17%, 7%, 15%, and 8%, respectively, when comparing nemiralisib with placebo [n = 15 (IL-5, IL-8) or 16 (IL-6, IL-13); posterior probability of a true ratio >0%: 78%, 64%, 76%, and 63%, respectively]. These results suggest that nemiralisib inhibited PI3Kδ locally; however, this did not translate into meaningful clinical improvement. Further studies will investigate the potential efficacy of nemiralisib in patients with asthma with other specific more severe phenotypes, including those who are colonized with bacteria and frequently exacerbate.
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Asma/tratamento farmacológico , Broncodilatadores/administração & dosagem , Indazóis/administração & dosagem , Indóis/administração & dosagem , Oxazóis/administração & dosagem , Piperazinas/administração & dosagem , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Adulto , Idoso , Asma/metabolismo , Estudos Cross-Over , Método Duplo-Cego , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Capacidade Vital/efeitos dos fármacos , Adulto JovemRESUMO
BACKGROUND: Domestication has played an important role in shaping characteristics of the inflorescence and plant height in cultivated cereals. Taking advantage of meta-analysis of QTLs, phylogenetic analyses in 502 diverse sorghum accessions, GWAS in a sorghum association panel (n = 354) and comparative data, we provide insight into the genetic basis of the domestication traits in sorghum and rice. RESULTS: We performed genome-wide association studies (GWAS) on 6 traits related to inflorescence morphology and 6 traits related to plant height in sorghum, comparing the genomic regions implicated in these traits by GWAS and QTL mapping, respectively. In a search for signatures of selection, we identify genomic regions that may contribute to sorghum domestication regarding plant height, flowering time and pericarp color. Comparative studies across taxa show functionally conserved 'hotspots' in sorghum and rice for awn presence and pericarp color that do not appear to reflect corresponding single genes but may indicate co-regulated clusters of genes. We also reveal homoeologous regions retaining similar functions for plant height and flowering time since genome duplication an estimated 70 million years ago or more in a common ancestor of cereals. In most such homoeologous QTL pairs, only one QTL interval exhibits strong selection signals in modern sorghum. CONCLUSIONS: Intersections among QTL, GWAS and comparative data advance knowledge of genetic determinants of inflorescence and plant height components in sorghum, and add new dimensions to comparisons between sorghum and rice.
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Oryza/genética , Proteínas de Plantas/genética , Sorghum/crescimento & desenvolvimento , Sorghum/genética , Evolução Molecular , Estudo de Associação Genômica Ampla , Inflorescência/crescimento & desenvolvimento , Dados de Sequência Molecular , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Fenótipo , Filogenia , Proteínas de Plantas/metabolismo , Locos de Características Quantitativas , Análise de Sequência de DNA , Sorghum/metabolismoRESUMO
Fossil records indicate that life appeared in marine environments â¼3.5 billion years ago (Gyr) and transitioned to terrestrial ecosystems nearly 2.5 Gyr. Sequence analysis suggests that "hydrobacteria" and "terrabacteria" might have diverged as early as 3 Gyr. Bacteria of the genus Azospirillum are associated with roots of terrestrial plants; however, virtually all their close relatives are aquatic. We obtained genome sequences of two Azospirillum species and analyzed their gene origins. While most Azospirillum house-keeping genes have orthologs in its close aquatic relatives, this lineage has obtained nearly half of its genome from terrestrial organisms. The majority of genes encoding functions critical for association with plants are among horizontally transferred genes. Our results show that transition of some aquatic bacteria to terrestrial habitats occurred much later than the suggested initial divergence of hydro- and terrabacterial clades. The birth of the genus Azospirillum approximately coincided with the emergence of vascular plants on land.
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Organismos Aquáticos/genética , Azospirillum/genética , Evolução Biológica , Ecossistema , Transferência Genética Horizontal/genética , Genoma Bacteriano/genética , Rhodospirillaceae/genética , Sequência de Bases , Genes Essenciais/genética , Glicosídeo Hidrolases/genética , Glicosídeo Hidrolases/metabolismo , Filogenia , Raízes de Plantas/microbiologia , RNA Ribossômico 16S/genéticaRESUMO
Skull base surgery is a young surgical subspecialty currently led by its second generation of surgeons. At present, there is no literature that narrates the connection of the present to the past. An extended interview was held with Dr Jon H. Robertson, who helped establish the subspecialty in Memphis, TN, to aid in identifying and connecting sentinel events and key figures in the development of the discipline. The field drastically evolved during his era of practice (1975-present), with the advent of advanced imaging and technology, as well as the emergence of multidisciplinary skull base surgical teams. The intersection of the careers of Jon H. Robertson, James T. Robertson, Gale Gardner, Edwin Cocke, John Shea, Jr., and Jerrall Crook in Memphis catalyzed the standardization of a multidisciplinary approach to cranial base pathology. We report the findings of Dr Jon H. Robertson's extended interview, told against the backdrop of the history of the subspecialty. The story of the development of skull base surgery is told from the unique perspective of one who lived and shaped a pivotal segment in this historical timeline.
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BAC-end sequences (BESs) of hybrid sugarcane cultivar R570 are presented. A total of 66,990 informative BESs were obtained from 43,874 BAC clones. Similarity search using a variety of public databases revealed that 13.5 and 42.8 % of BESs match known gene-coding and repeat regions, respectively. That 11.7 % of BESs are still unmatched to any nucleotide sequences in the current public databases despite the fact that a close relative, sorghum, is fully sequenced, indicates that there may be many sugarcane-specific or lineage-specific sequences. We found 1,742 simple sequence repeat motifs in 1,585 BESs, spanning 27,383 bp in length. As simple sequence repeat markers derived from BESs have some advantages over randomly generated markers, these may be particularly useful for comparing BAC-based physical maps with genetic maps. BES and overgo hybridization information was used for anchoring sugarcane BAC clones to the sorghum genome sequence. While sorghum and sugarcane have extensive similarity in terms of genomic structure, only 2,789 BACs (6.4 %) could be confidently anchored to the sorghum genome at the stringent threshold of having both-end information (BESs or overgos) within 300 Kb. This relatively low rate of anchoring may have been caused in part by small- or large-scale genomic rearrangements in the Saccharum genus after two rounds of whole genome duplication since its divergence from the sorghum lineage about 7.8 million years ago. Limiting consideration to only low-copy matches, 1,245 BACs were placed to 1,503 locations, covering ~198 Mb of the sorghum genome or about 78 % of the estimated 252 Mb of euchromatin. BESs and their analyses presented here may provide an early profile of the sugarcane genome as well as a basis for BAC-by-BAC sequencing of much of the basic gene set of sugarcane.
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Saccharum/genética , Sequência de Bases , Mapeamento Cromossômico , Cromossomos Artificiais Bacterianos/genética , Cromossomos de Plantas/genética , DNA de Plantas/genética , Bases de Dados Genéticas , Eucromatina/genética , Genoma de Planta , Repetições de Microssatélites , Sorghum/genética , Especificidade da EspécieRESUMO
Episodic memory deficits are a core feature of neurodegenerative disorders. Muscarinic M(1) receptors play a critical role in modulating learning and memory and are highly expressed in the hippocampus. We examined the effect of GSK1034702, a potent M(1) receptor allosteric agonist, on cognitive function, and in particular episodic memory, in healthy smokers using the nicotine abstinence model of cognitive dysfunction. The study utilized a randomized, double-blind, placebo-controlled, cross-over design in which 20 male nicotine abstained smokers were tested following single doses of placebo, 4 and 8 mg GSK1034702. Compared to the baseline (nicotine on-state), nicotine abstinence showed statistical significance in reducing immediate (p=0.019) and delayed (p=0.02) recall. GSK1034702 (8 mg) significantly attenuated (i.e. improved) immediate recall (p=0.014) but not delayed recall. None of the other cognitive domains was modulated by either nicotine abstinence or GSK1034702. These findings suggest that stimulating M(1) receptor mediated neurotransmission in humans with GSK1034702 improves memory encoding potentially by modulating hippocampal function. Hence, selective M(1) receptor allosteric agonists may have therapeutic benefits in disorders of impaired learning including Alzheimer's disease.
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Comportamento Aditivo/psicologia , Benzimidazóis/uso terapêutico , Transtornos Cognitivos/psicologia , Memória Episódica , Receptor Muscarínico M1/agonistas , Abandono do Hábito de Fumar/psicologia , Adulto , Regulação Alostérica/efeitos dos fármacos , Regulação Alostérica/fisiologia , Comportamento Aditivo/tratamento farmacológico , Benzimidazóis/farmacologia , Transtornos Cognitivos/tratamento farmacológico , Estudos Cross-Over , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , Nicotina , Receptor Muscarínico M1/fisiologia , Fumar/psicologia , Adulto JovemRESUMO
Glioblastoma multiforme (GBM) is the most common and devastating form of primary central nervous system malignancy. The prognosis for patients diagnosed with GBM is poor, having a median survival rate of 12-15 months. Despite modern advances in the development of antineoplastic agents, the efficacy of newer anti-cancer agents in the treatment of GBM is yet to be determined. Thus, there remains a significant unmet need for new therapeutic strategies against GBM. A promising chemotherapeutic intervention has emerged from studies of cannabinoid receptor agonists wherein tetrahydrocannabinol has been the most extensively studied. The novel cannabinoid ligand KM-233 was developed as a lead platform for future optimization of biopharmaceutical properties of classical based cannabinoid ligands. Treatment of U87MG human GBM cells with KM-233 caused a time dependent change in the phosphorylation profiles of MEK, ERK1/2, Akt, BAD, STAT3, and p70S6K. Almost complete mitochondrial depolarization was observed 6 h post-treatment followed by a rapid increase in cleaved caspase 3 and significant cytoskeletal contractions. Treatment with KM-233 also resulted in a redistribution of the Golgi-endoplasmic reticulum structures. Dose escalation studies in the orthotopic model using U87MG cells revealed an 80 % reduction in tumor size after 12 mg/kg daily dosing for 20 days. The evaluation of KM-233 against primary tumor tissue in the side flank model revealed a significant decrease in the rate of tumor growth. These findings indicate that structural refinement of KM-233 to improve its biopharmaceutical properties may lead to a novel and efficacious treatment for GBM.
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Neoplasias Encefálicas/tratamento farmacológico , Canabinoides/uso terapêutico , Glioma/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Caspase 3/metabolismo , Modelos Animais de Doenças , Feminino , Glioma/metabolismo , Glioma/patologia , Humanos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Fosfoproteínas/metabolismo , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/metabolismo , Células Tumorais CultivadasRESUMO
A young man with type 1 neurofibromatosis presented with progressive myelopathy. Imaging revealed an anterolateral mass within the spinal canal at C1-2, with severe compression of the spinal cord. A far-lateral approach was used to remove the mass, which proved to be an extradural neurofibroma. This narrated stereoscopic video details the important steps of the operation. The video can be found here: http://youtu.be/td4MjLtiMbk .
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Sugarcane (Saccharum spp.) breeders in the early 20th century made remarkable progress in increasing yield and disease resistance by crossing Saccharum spontaneum L., a wild relative, to Saccharum officinarum L., a traditional cultivar. Modern sugarcane cultivars have approximately 71%-83% of their chromosomes originating from S. officinarum, approximately 10%-21% from S. spontaneum, and approximately 2%-13% recombinant or translocated chromosomes. In the present work, C(0)t-based cloning and sequencing (CBCS) was implemented to further explore highly repetitive DNA and to seek species-specific repeated DNA in both S. officinarum and S. spontaneum. For putatively species-specific sequences, overlappping oligonucleotide probes (overgos) were designed and hybridized to BAC filters from the interspecific hybrid sugarcane cultivar 'R570' to try to deduce parental origins of BAC clones. We inferred that 12 967 BACs putatively originated from S. officinarum and 5117 BACs from S. spontaneum. Another 1103 BACs were hybridized by both species-specific overgos, too many to account for by conventional recombination, thus suggesting ectopic recombination and (or) translocation of DNA elements. Constructing a low C(0)t library is useful to collect highly repeated DNA sequences and to search for potentially species-specific molecular markers, especially among recently diverged species. Even in the absence of repeat families that are species-specific in their entirety, the identification of localized variations within consensus sequences, coupled with the site specificity of short synthetic overgos, permits researchers to monitor species-specific or species-enriched variants.
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Cromossomos Artificiais Bacterianos/genética , Sequências Repetitivas de Ácido Nucleico/genética , Saccharum/genética , Sequência de Bases , Mapeamento Cromossômico , Cromossomos de Plantas , DNA de Plantas/genética , Biblioteca Gênica , Genoma de Planta , Hibridização in Situ Fluorescente , Dados de Sequência Molecular , Análise de Sequência de DNA , Especificidade da EspécieRESUMO
Introduction Lesions of the jugular foramen (JF) and postero-lateral skull base are difficult to expose and exhibit complex neurovascular relationships. Given their rarity and the increasing use of radiosurgery, neurosurgeons are becoming less experienced with their surgical management. Anatomical factors are crucial in designing the approach to achieve a maximal safe resection. Methods and methods Six cadaveric heads (12 sides) were dissected via combined post-auricular infralabyrinthine and distal transcervical approach with additional anterior transstyloid and posterior far lateral exposures. Contiguous surgical triangles were measured, and contents were analyzed. Thirty-one patients (32 lesions) were treated surgically between 2000 and 2016 through different variations of the retro-auricular distal cervical transtemporal approaches. Results We anatomically reviewed the carotid, stylodigastric, jugular, condylar, suboccipital, deep condylar, mastoid, suprajugular, suprahypoglossal (infrajugular), and infrahypoglossal triangles. Tumors included glomus jugulare, lower cranial nerve schwannomas or neurofibromas, meningiomas, chondrosarcoma, adenocystic carcinoma, plasmacytoma of the occipitocervical joint, and a sarcoid lesion. We classified tumors into extracranial, intradural, intraosseous, and dumbbell-shaped, and analyzed the approach selection for each. Conclusion Jugular foramen and posterolateral skull base lesions can be safely resected through a retro-auricular distal cervical lateral skull base approach, which is customizable to anatomical location and tumor extension by tailoring the involved osteo-muscular triangles.
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Tillering and secondary branching are two plastic traits with high agronomic importance, especially in terms of the ability of plants to adapt to changing environments. We describe a quantitative trait analysis of tillering and secondary branching in two novel BC1F2 populations totaling 246 genotypes derived from backcrossing two Sorghum bicolor x S. halepense F1 plants to a tetraploidized S. bicolor. A two-year, two-environment phenotypic evaluation in Bogart, GA and Salina, KS permitted us to identify major effect and environment specific QTLs. Significant correlation between tillering and secondary branching followed by discovery of overlapping sets of QTLs continue to support the developmental relationship between these two organs and suggest the possibility of pleiotropy. Comparisons with two other populations sharing S. bicolor BTx623 as a common parent but sampling the breadth of the Sorghum genus, increase confidence in QTL detected for these two plastic traits and provide insight into the evolution of morphological diversity in the Eusorghum clade. Correspondence between flowering time and vegetative branching supports other evidence in suggesting a pleiotropic effect of flowering genes. We propose a model to predict biomass weight from plant architecture related traits, quantifying contribution of each trait to biomass and providing guidance for future breeding experiments.
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Melhoramento Vegetal , Sorghum , Mapeamento Cromossômico , Fenótipo , Locos de Características QuantitativasRESUMO
Background: Management of acute exacerbations of chronic obstructive pulmonary disease (COPD) is sometimes inadequate leading to either prolonged duration and/or an increased risk of recurrent exacerbations in the period following the initial event. Objective: To evaluate the safety and efficacy of inhaled nemiralisib, a phosphoinositide 3-kinase δ inhibitor, in patients experiencing an acute exacerbation of COPD. Patients and Methods: In this double-blind, placebo-controlled study, COPD patients (40-80 years, ≥10 pack-year smoking history, current moderate/severe acute exacerbation of COPD requiring standard-of-care treatment) were randomized to placebo or nemiralisib 12.5 µg, 50 µg, 100 µg, 250 µg, 500 µg, or 750 µg (ratio of 3:1:1:1:1:1:3; N=938) for 12 weeks with an exploratory 12-week follow-up period. The primary endpoint was change from baseline in post-bronchodilator FEV1 at week 12. Key secondary endpoints were rate of re-exacerbations, patient-reported outcomes (Exacerbations of Chronic Pulmonary Disease Tool, COPD Assessment Test, St George's Respiratory Questionnaire-COPD), plasma pharmacokinetics (PK) and safety/tolerability. Results: There was no difference in change from baseline FEV1 at week 12 between the nemiralisib and placebo treatment groups (posterior adjusted median difference, nemiralisib 750 µg and placebo: -0.004L (95% CrI: -0.051L to 0.042L)). Overall, there were also no differences between nemiralisib and placebo in secondary endpoints, including re-exacerbations. Plasma PK increased in a dose proportional manner. The most common adverse event for nemiralisib was post-inhalation cough which appeared to be dose-related. Conclusion: The addition of nemiralisib to standard-of-care treatment for 12 weeks did not improve lung function or re-exacerbations in patients with, and following an acute exacerbation of COPD. However, this study demonstrated that large clinical trials recruiting acutely exacerbating patients can successfully be conducted.
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Fosfatidilinositol 3-Quinases , Doença Pulmonar Obstrutiva Crônica , Broncodilatadores/uso terapêutico , Método Duplo-Cego , Volume Expiratório Forçado , Humanos , Indazóis , Indóis , Oxazóis/farmacologia , Oxazóis/uso terapêutico , Fosfatidilinositol 3-Quinases/farmacologia , Fosfatidilinositol 3-Quinases/uso terapêutico , Piperazinas , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológicoRESUMO
Purpose: This study evaluated the safety and efficacy of inhaled nemiralisib, a phosphoinositide 3-kinase δ (PI3Kδ) inhibitor, in patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD). Methods: In this double-blind, placebo-controlled study, 126 patients (40-80 years with a post-bronchodilator forced expiratory volume in 1 sec (FEV1) ≤80% of predicted (previously documented)) were randomized 1:1 to once daily inhaled nemiralisib (1 mg) or placebo for 84 days, added to standard of care. The primary endpoint was specific imaging airway volume (siVaw) after 28 treatment days and was analyzed using a Bayesian repeated measures model (clintrials.gov: NCT02294734). Results: A total of 126 patients were randomized to treatment; 55 on active treatment and 49 on placebo completed the study. When comparing nemiralisib and placebo-treated patients, an 18% placebo-corrected increase from baseline in distal siVaw (95% credible intervals (Cr I) (-1%, 42%)) was observed on Day 28. The probability that the true treatment ratio was >0% (Pr(θ>0)) was 96%, suggestive of a real treatment effect. Improvements were observed across all lung lobes. Patients treated with nemiralisib experienced a 107.3 mL improvement in posterior median FEV1 (change from baseline, 95% Cr I (-2.1, 215.5)) at day 84, compared with placebo. Adverse events were reported by 41 patients on placebo and 49 on nemiralisib, the most common being post-inhalation cough on nemiralisib (35%) vs placebo (3%). Conclusion: These data show that addition of nemiralisib to usual care delivers more effective recovery from an acute exacerbation and improves lung function parameters including siVaw and FEV1. Although post-inhalation cough was identified, nemiralisib was otherwise well tolerated, providing a promising novel therapy for this acutely ill patient group.
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Fosfatidilinositol 3-Quinases , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Teorema de Bayes , Broncodilatadores/uso terapêutico , Método Duplo-Cego , Volume Expiratório Forçado , Humanos , Fosfatidilinositol 3-Quinases/farmacologia , Fosfatidilinositol 3-Quinases/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Resultado do TratamentoRESUMO
Betula L. (birch) is a pioneer hardwood tree species with ecological, economic, and evolutionary importance in the Northern Hemisphere. We sequenced the Betula platyphylla genome and assembled the sequences into 14 chromosomes. The Betula genome lacks evidence of recent whole-genome duplication and has the same paleoploidy level as Vitis vinifera and Prunus mume. Phylogenetic analysis of lignin pathway genes coupled with tissue-specific expression patterns provided clues for understanding the formation of higher ratios of syringyl to guaiacyl lignin observed in Betula species. Our transcriptome analysis of leaf tissues under a time-series cold stress experiment revealed the presence of the MEKK1-MKK2-MPK4 cascade and six additional mitogen-activated protein kinases that can be linked to a gene regulatory network involving many transcription factors and cold tolerance genes. Our genomic and transcriptome analyses provide insight into the structures, features, and evolution of the B. platyphylla genome. The chromosome-level genome and gene resources of B. platyphylla obtained in this study will facilitate the identification of important and essential genes governing important traits of trees and genetic improvement of B. platyphylla.
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BACKGROUND: Flowering is one of the most important processes for flowering plants such as cotton, reflecting the transition from vegetative to reproductive growth and is of central importance to crop yield and adaptability. Conventionally, categorical scoring systems have been widely used to study flowering patterns, which are laborious and subjective to apply. The goal of this study was to develop a deep learning-based approach to characterize flowering patterns for cotton plants that flower progressively over several weeks, with flowers distributed across much of the plant. RESULTS: A ground mobile system (GPhenoVision) was modified with a multi-view color imaging module, to acquire images of a plant from four viewing angles at a time. A total of 116 plants from 23 genotypes were imaged during an approximately 2-month period with an average scanning interval of 2-3 days, yielding a dataset containing 8666 images. A subset (475) of the images were randomly selected and manually annotated to form datasets for training and selecting the best object detection model. With the best model, a deep learning-based approach (DeepFlower) was developed to detect and count individual emerging blooms for a plant on a given date. The DeepFlower was used to process all images to obtain bloom counts for individual plants over the flowering period, using the resulting counts to derive flowering curves (and thus flowering characteristics). Regression analyses showed that the DeepFlower method could accurately (R2 = 0.88 and RMSE = 0.79) detect and count emerging blooms on cotton plants, and statistical analyses showed that imaging-derived flowering characteristics had similar effectiveness as manual assessment for identifying differences among genetic categories or genotypes. CONCLUSIONS: The developed approach could thus be an effective and efficient tool to characterize flowering patterns for flowering plants (such as cotton) with complex canopy architecture.
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Despite a "ploidy barrier," interspecific crosses to wild and/or cultivated sorghum (Sorghum bicolor, 2n = 2x = 20) may have aided the spread across six continents of Sorghum halepense, also exemplifying risks of "transgene escape" from crops that could make weeds more difficult to control. Genetic maps of two BC1F1 populations derived from crosses of S. bicolor (sorghum) and S. halepense with totals of 722 and 795 single nucleotide polymorphism (SNP) markers span 37 and 35 linkage groups, with 2-6 for each of the 10 basic sorghum chromosomes due to fragments covering different chromosomal portions or independent segregation from different S. halepense homologs. Segregation distortion favored S. halepense alleles on chromosomes 2 (1.06-4.68 Mb, near a fertility restoration gene), 7 (1.20-6.16 Mb), 8 (1.81-5.33 Mb, associated with gene conversion), and 9 (47.5-50.1 Mb); and S. bicolor alleles on chromosome 6 (0-40 Mb), which contains both a large heterochromatin block and the Ma1 gene. Regions of the S. halepense genome that are recalcitrant to gene flow from sorghum might be exploited as part a multi-component system to reduce the likelihood of spread of transgenes or other modified genes. Its SNP profile suggests that chromosome segments from its respective progenitors S. bicolor and Sorghum propinquum have extensively recombined in S. halepense. This study reveals genomic regions that might discourage crop-to-weed gene escape, and provides a foundation for marker-trait association analysis to determine the genetic control of traits contributing to weediness, invasiveness, and perenniality of S. halepense.
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OBJECTIVE: The Neurosurgery Research & Education Foundation (NREF), previously known as the Research Foundation of the American Association of Neurological Surgeons (AANS), was established in 1980 to encourage and facilitate innovation through financial support to young neurosurgeons in the process of honing their competencies in neurosciences and neurological surgery. This article provides a historical overview of NREF, its mission, and charitable contributions and the ever-expanding avenues for neurosurgeons, neurosurgical residents and fellows, and medical students to supplement clinical training and to further neurosurgical research advances. METHODS: Data were collected from the historical archives of the AANS and NREF website. Available data included tabulated revenue, geographic and institutional records of funding, changes in funding for fellowships and awards, advertising methods, and sources of funding. RESULTS: Since 1984, NREF has invested more than $23 million into the future of neurosurgery. To date, NREF has provided more than 500 fellowship opportunities which have funded neurosurgeons' education and research efforts at all stages of training and practice. CONCLUSIONS: NREF is designed to serve as the vehicle through which the neurosurgical community fosters the continued excellence in the care of patients with neurosurgical diseases.