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BACKGROUND: Cabotegravir plus rilpivirine (CAB + RPV) is a guideline-recommended long-acting (LA) injectable regimen for the maintenance of human immunodeficiency virus-1 (HIV-1) virologic suppression. This post hoc analysis summarizes CAB + RPV LA results by baseline body mass index (BMI) category among phase 3/3b trial participants. METHODS: Data from CAB + RPV-naive participants receiving every 4 or 8 week dosing in FLAIR, ATLAS, and ATLAS-2M were pooled through week 48. Data beyond week 48 were summarized by study (FLAIR through week 96 and ATLAS-2M through week 152). HIV-1 RNA <50 and ≥50â copies/mL, confirmed virologic failure (CVF; 2 consecutive HIV-1 RNA ≥200â copies/mL), safety and tolerability, and plasma CAB and RPV trough concentrations were evaluated by baseline BMI (<30â kg/m2, lower; ≥30â kg/m2, higher). RESULTS: Among 1245 CAB + RPV LA participants, 213 (17%) had a baseline BMI ≥30â kg/m2. At week 48, 92% versus 93% of participants with lower versus higher BMI had HIV-1 RNA <50â copies/mL, respectively. Including data beyond week 48, 18 participants had CVF; those in the higher BMI group (n = 8) all had at least 1 other baseline factor associated with CVF (archived RPV resistance-associated mutations or HIV-1 subtype A6/A1). Safety and pharmacokinetic profiles were comparable between BMI categories. CONCLUSIONS: CAB + RPV LA was efficacious and well tolerated, regardless of baseline BMI category. CLINICAL TRIALS REGISTRATION: NCT02938520, NCT02951052, and NCT03299049.
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Fármacos Anti-VIH , Índice de Masa Corporal , Infecciones por VIH , VIH-1 , Piridonas , Rilpivirina , Humanos , Rilpivirina/farmacocinética , Rilpivirina/uso terapéutico , Rilpivirina/administración & dosificación , Rilpivirina/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Masculino , VIH-1/efectos de los fármacos , Femenino , Fármacos Anti-VIH/farmacocinética , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Adulto , Persona de Mediana Edad , Piridonas/farmacocinética , Piridonas/administración & dosificación , Piridonas/efectos adversos , Carga Viral/efectos de los fármacos , ARN Viral/sangre , Resultado del Tratamiento , Quimioterapia Combinada , DicetopiperazinasRESUMEN
OBJECTIVE: To understand factors associated with missed academic time after concussion to improve support for patients. Our goal was to assess patient-specific predictors of total school time lost after pediatric/adolescent concussion. STUDY DESIGN: We performed a prospective cohort study of children and adolescents (8-18 years of age) seen within 14 days of concussion from seven pediatric medical centers across the United States. We collected outcomes via the Concussion Learning Assessment & School Survey (CLASS) and constructed a multivariable predictive model evaluating patient factors associated with school time loss. RESULTS: 167 patients participated (mean age = 14.5 ± 2.2 years; 46% female). Patients were assessed initially at 5.0 ± 3.0 days post-injury and had a final follow-up assessment 24.5 ± 20.0 days post-concussion. Participants missed a median of 2 days of school (IQR = 0.5-4), and 21% reported their grades dropped after concussion. Higher initial symptom severity rating (ß = 0.06, 95% CI = 0.03-0.08, p < 0.001) and perception of grades dropping after concussion (ß = 1.37, 95% CI = 0.28-2.45, p = 0.01) were significantly associated with more days of school time missed after concussion. Those who reported their grades dropping reported missing significantly more school (mean = 5.0, SD = 4.7 days missed of school) than those who reported their grades did not drop (mean = 2.2, SD = 2.6 days missed of school; p < 0.001; Cohen's d = 0.87). CONCLUSIONS: Children and adolescents reported missing a median of 2 days of school following concussion, and more missed school time after a concussion was associated with more severe concussion symptoms and perception of grades dropping. These findings may support recommendations for minimal delays in return-to-learn after concussion.
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BACKGROUND: Postoperative pediatric cerebellar mutism syndrome (CMS) may occur following a process affecting the posterior cranial fossa. Recent evidence demonstrates disabling and potentially lasting motor components of this syndrome, including ataxia, hemiparesis, and oculomotor dysfunction. These impairments may contribute to vestibular deficits. METHODS: This case series contributes data to quantify vestibular dysfunction in postoperative CMS. The pair consisted of one female and one male. RESULTS: Vestibular testing demonstrated both peripheral and central dysfunction. CONCLUSIONS: Given these findings, a thorough vestibular assessment may be indicated as part of a comprehensive evaluation following a postoperative CMS diagnosis. Further research is needed to understand the pathophysiology, treatment, and long-term outcomes of postoperative pediatric CMS.
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Enfermedades Cerebelosas , Neoplasias Cerebelosas , Mutismo , Niño , Humanos , Masculino , Femenino , Mutismo/diagnóstico , Mutismo/etiología , Neoplasias Cerebelosas/cirugía , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Enfermedades Cerebelosas/diagnóstico , Enfermedades Cerebelosas/etiología , Fosa Craneal Posterior , SíndromeRESUMEN
This report describes a 15-year-old female with known spastic and dystonic quadriplegic cerebral palsy (CP), Gross Motor Function Classification System IV, and obstructive sleep apnea (OSA). She experienced decreased apneic episodes after receiving onabotulinumtoxin A (BoNT-A) injections for the treatment of oromandibular dystonia (OMD). After her OSA diagnosis, she initially received injections to the bilateral masseter and temporalis muscles with no effect on the frequency of nightly apneic episodes. Subsequently, the bilateral lateral pterygoid muscles were added and she was later noted to have fewer apneic episodes overnight. This case report describes the use of BoNT-A in the muscles of mastication for management of OMD and the ensuing improvement in OSA in a teenager with CP.
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Toxinas Botulínicas Tipo A , Parálisis Cerebral , Distonía , Trastornos Distónicos , Fármacos Neuromusculares , Apnea Obstructiva del Sueño , Femenino , Adolescente , Humanos , Toxinas Botulínicas Tipo A/uso terapéutico , Distonía/complicaciones , Distonía/tratamiento farmacológico , Parálisis Cerebral/complicaciones , Parálisis Cerebral/tratamiento farmacológico , Fármacos Neuromusculares/uso terapéuticoRESUMEN
Plant metaxylem vessels provide physical support to promote upright growth and the transport of water and nutrients. A detailed characterization of the molecular network controlling metaxylem development is lacking. However, knowledge of the events that regulate metaxylem development could contribute to the development of germplasm with improved yield. In this paper, we screened an EMS-induced B73 mutant library, which covers 92% of maize (Zea mays) genes, to identify drought-sensitive phenotypes. Three mutants were identified, named iqd27-1, iqd27-2, and iqd27-3, and genetic crosses showed that they were allelic to each other. The causal gene in these 3 mutants encodes the IQ domain-containing protein ZmIQD27. Our study showed that defective metaxylem vessel development likely causes the drought sensitivity and abnormal water transport phenotypes in the iqd27 mutants. ZmIQD27 was expressed in the root meristematic zone where secondary cell wall deposition is initiated, and loss-of-function iqd27 mutants exhibited a microtubular arrangement disorder. We propose that association of functional ZmIQD27 with microtubules is essential for correct targeted deposition of the building blocks for secondary cell wall development in maize.
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Meristema , Zea mays , Zea mays/metabolismo , Plantones/genética , Sequías , Agua/metabolismoRESUMEN
Plant architecture, lodging resistance, and yield are closely associated with height. In this paper, we report the identification and characterization of two allelic EMS-induced mutants of Zea mays, xyl-1, and xyl-2 that display dwarf phenotypes. The mutated gene, ZmXYL, encodes an α-xylosidase which functions in releasing xylosyl residue from a ß-1,4-linked glucan chain. Total α-xylosidase activity in the two alleles is significantly decreased compared to wild-type plants. Loss-of-function mutants of ZmXYL resulted in a decreased xylose content, an increased XXXG content in xyloglucan (XyG), and a reduced auxin content. We show that auxin has an antagonistic effect with XXXG in promoting cell divisions within mesocotyl tissue. xyl-1 and xyl-2 were less sensitive to IAA compared to B73. Based on our study, a model is proposed that places XXXG, an oligosaccharide derived from XyG and the substrate of ZmXYL, as having a negative impact on auxin homeostasis resulting in the dwarf phenotypes of the xyl mutants. Our results provide a insight into the roles of oligosaccharides released from plant cell walls as signals in mediating plant growth and development.
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Xilosidasas , Zea mays , Zea mays/genética , Ácidos Indolacéticos , Oligosacáridos/química , Plantas/genéticaRESUMEN
Modeling of biological domains and simulation of biophysical processes occurring in them can help inform medical procedures. However, when considering complex domains such as large regions of the human body, the complexities of blood vessel branching and variation of blood vessel dimensions present a major modeling challenge. Here, we present a Voxelized Multi-Physics Simulation (VoM-PhyS) framework to simulate coupled heat transfer and fluid flow using a multi-scale voxel mesh on a biological domain obtained. In this framework, flow in larger blood vessels is modeled using the Hagen-Poiseuille equation for a one-dimensional flow coupled with a three-dimensional two-compartment porous media model for capillary circulation in tissue. The Dirac distribution function is used as Sphere of Influence (SoI) parameter to couple the one-dimensional and three-dimensional flow. This blood flow system is coupled with a heat transfer solver to provide a complete thermo-physiological simulation. The framework is demonstrated on a frog tongue and further analysis is conducted to study the effect of convective heat exchange between blood vessels and tissue, and the effect of SoI on simulation results.
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Circulación Sanguínea/fisiología , Temperatura Corporal/fisiología , Cuerpo Humano , Modelos Biológicos , Capilares , Simulación por Computador , Calor , Humanos , Imagenología TridimensionalRESUMEN
Salicylic acid (SA) is a key phytohormone regulating plant immunity. Although the transcriptional regulation of SA biosynthesis has been well-studied, its post-translational regulation is largely unknown. We report that a Kelch repeats-containing F-box (KFB) protein, SMALL AND GLOSSY LEAVES 1 (SAGL1), negatively influences SA biosynthesis in Arabidopsis thaliana by mediating the proteolytic turnover of SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1 (SARD1), a master transcription factor that directly drives SA biosynthesis during immunity. Loss of SAGL1 resulted in characteristic growth inhibition. Combining metabolomic, transcriptional and phenotypic analyses, we found that SAGL1 represses SA biosynthesis and SA-mediated immune activation. Genetic crosses to mutants that are deficient in SA biosynthesis blocked the SA overaccumulation in sagl1 and rescued its growth. Biochemical and proteomic analysis identified that SAGL1 interacts with SARD1 and promotes the degradation of SARD1 in a proteasome-dependent manner. These results unravelled a critical role of KFB protein SAGL1 in maintaining SA homeostasis via controlling SARD1 stability.
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Proteínas de Arabidopsis , Arabidopsis , Proteínas F-Box , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas F-Box/genética , Regulación de la Expresión Génica de las Plantas , Inmunidad de la Planta , Proteómica , Ácido Salicílico/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
OBJECTIVES: Long-acting formulations of cabotegravir (CAB) and rilpivirine (RPV) have demonstrated efficacy in Phase 3 studies. POLAR (NCT03639311) assessed antiviral activity and safety of CAB+RPV long-acting administered every 2âmonths (Q2M) in adults living with HIV-1 who previously received daily oral CAB+RPV in LATTE (NCT01641809). DESIGN: A Phase 2b, multicenter, open-label, rollover study. METHODS: LATTE participants with plasma HIV-1 RNA less than 50âcopies/ml who completed at least 300âweeks on study were eligible. Participants elected to switch to either CAB+RPV long-acting Q2M or daily oral dolutegravir/RPV for maintenance of virologic suppression. The primary endpoint was the proportion of participants with HIV-1 RNA greater than or equal to 50âcopies/ml at Month 12 (M12) per the Food and Drug Administration Snapshot algorithm. The incidence of confirmed virologic failure (CVF, two consecutive HIV-1 RNA measurements greater than or equal to 200âcopies/ml), as well as safety, laboratory, and patient-reported outcomes (HIV Treatment Satisfaction and preference questionnaires) were also assessed. RESULTS: Of 97 participants enrolled, 90 chose to receive CAB+RPV long-acting and seven chose dolutegravir/RPV. At M12, no participant had HIV-1 RNA greater than or equal to 50âcopies/ml or met the CVF criterion in either treatment group. No new safety signals were identified. Total treatment satisfaction was high at Baseline and remained stable through M12 across both treatment groups. Overall, 88% (nâ=â77/88) of long-acting arm participants preferred CAB+RPV long-acting to oral CAB+RPV. CONCLUSION: CAB+RPV long-acting maintained virologic suppression in participants who had previously received daily oral CAB+RPV for at least 5âyears in LATTE, with a favorable safety profile. Most participants preferred CAB+RPV long-acting to their prior oral CAB+RPV regimen at M12.
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Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Adulto , Fármacos Anti-VIH/uso terapéutico , Dicetopiperazinas , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Humanos , Piridonas/uso terapéutico , Rilpivirina/uso terapéuticoRESUMEN
ERECTA PANICLE 3 (EP3) and ORYZA SATIVA F-BOX KELCH 1 (OsFBK1) proteins share 57% and 54% sequence identity with the Arabidopsis F-box protein HAWAIIAN SKIRT (HWS). Previously we showed that EP3 is a functional orthologue of HWS. Here we demonstrate that OsFBK1 is another functional orthologue of HWS and show the complexity of interaction between EP3 and OsFBK1 genes at different developmental stages of the plant. qRT-PCR expression analyses and studies of EP3-GFP and OsFBK1-RFP promoter reporter lines demonstrate that although EP3 and OsFBK1 expression can be detected in the same tissues some cells exclusively express EP3 or OsFBK1 whilst others co-express both genes. Loss, reduction or gain-of-function lines for EP3 and OsFBK1, show that EP3 and OsFBK1 affect plant architecture, organ size, floral organ number and size, floral morphology, pollen viability, grain size and weight. We have identified the putative orthologue genes of the rice microRNA pathway for ORYZA SATIVA DAWDLE (OsDDL) and ORYZA SATIVA SERRATE (OsSE), and demonstrated that EP3 and OsFBK1 affect their transcript levels as well as those of CROWN ROOT DEFECT 1/ORYZA SATIVA Exportin-5 HASTY (CRD1/OsHST), ORYZA SATIVA DICER-LIKE 1 (OsDCL) and ORYZA SATIVA WEAVY LEAF1 (OsWAF1). We show that EP3 affects OsPri-MIR164, OsNAM1 and OsNAC1 transcript levels. OsNAC1 transcripts are modified by OsFBK1, suggesting two independent regulatory pathways, one via EP3 and OsMIR164 and the other via OsFBK1. Our data propose that EP3 and OsFBK1 conjointly play similar roles in rice to how HWS does in Arabidopsis.
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Arabidopsis , MicroARNs , Oryza , Arabidopsis/metabolismo , Flores , Regulación de la Expresión Génica de las Plantas/genética , MicroARNs/genética , MicroARNs/metabolismo , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
With diverse genetic backgrounds, soybean landraces are valuable resource for breeding programs. Herein, we apply multi-omic approaches to extensively characterize the molecular basis of drought tolerance in the soybean landrace LX. Initial screens established that LX performed better with PEG6000 treatment than control cultivars. LX germinated better than William 82 under drought conditions and accumulated more anthocyanin and flavonoids. Untargeted mass spectrometry in combination with transcriptomic analyses revealed the chemical diversity and genetic basis underlying the overall performance of LX landrace. Under control and drought conditions, significant differences in the expression of a suite of secondary metabolism genes, particularly those involved in the general phenylpropanoid pathway and flavonoid but not lignin biosynthesis, were seen in LX and William 82. The expression of these genes correlated with the corresponding metabolites in LX plants. Further correlation analysis between metabolites and transcripts identified pathway structural genes and transcription factors likely are responsible for the LX agronomic traits. The activities of some key biosynthetic genes or regulators were confirmed through heterologous expression in transgenic Arabidopsis and hairy root transformation in soybean. We propose a regulatory mechanism based on flavonoid secondary metabolism and adaptive traits of this landrace which could be of relevance to cultivated soybean.
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Sequías , Genómica , Glycine max/fisiología , Carácter Cuantitativo Heredable , Antocianinas/biosíntesis , Flavonoides/biosíntesis , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Germinación/fisiología , Metaboloma/genética , Metabolómica , Fenotipo , Propanoles/metabolismo , Reproducibilidad de los Resultados , Metabolismo Secundario/genética , Glycine max/genética , Estrés Fisiológico/genética , Factores de Transcripción/metabolismo , Transcriptoma/genéticaRESUMEN
BACKGROUND: Long-acting (LA) injectable regimens are a potential therapeutic option in people living with HIV-1. SETTING: ATLAS (NCT02951052) and FLAIR (NCT02938520) were 2 randomized, open-label, multicenter, multinational phase 3 studies. METHODS: Adult participants with virologic suppression (plasma HIV-1 RNA <50 copies/mL) were randomized (1:1) to continue with their current antiretroviral regimen (CAR) or switch to the long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). In the LA arm, participants initially received oral CAB + RPV once-daily for 4 weeks to assess individual safety and tolerability, before starting monthly injectable therapy. The primary endpoint of this combined analysis was antiviral efficacy at week 48 (FDA Snapshot algorithm: noninferiority margin of 4% for HIV-1 RNA ≥50 copies/mL). Safety, tolerability, and confirmed virologic failure (2 consecutive plasma HIV-1 RNA ≥200 copies/mL) were secondary endpoints. RESULTS: The pooled intention-to-treat exposed population included 591 participants in each arm [28% women (sex at birth), 19% aged ≥50 years]. Noninferiority criteria at week 48 were met for the primary (HIV-1 RNA ≥50 copies/mL) and key secondary (HIV-1 RNA <50 copies/mL) efficacy endpoints. Seven individuals in each arm (1.2%) developed confirmed virologic failure; 6/7 (LA) and 3/7 (CAR) had resistance-associated mutations. Most LA recipients (83%) experienced injection site reactions, which decreased in incidence over time. Injection site reactions led to the withdrawal of 6 (1%) participants. The serious adverse event rate was 4% in each arm. CONCLUSION: This combined analysis demonstrates monthly injections of CAB + RPV LA were noninferior to daily oral CAR for maintaining HIV-1 suppression.
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Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Rilpivirina/administración & dosificación , Rilpivirina/uso terapéutico , Adulto , Anciano , Fármacos Anti-VIH/efectos adversos , Preparaciones de Acción Retardada , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rilpivirina/efectos adversos , Adulto JovenRESUMEN
Determining the genetic rearrangement and domestication footprints in Gossypium hirsutum cultivars and primitive race genotypes are essential for effective gene conservation efforts and the development of advanced breeding molecular markers for marker-assisted breeding. In this study, 94 accessions representing the 7 primitive races of G hirsutum, along with 9 G hirsutum and 12 Gossypium barbadense cultivated accessions were evaluated. The genotyping-by-sequencing (GBS) approach was employed and 146 558 single nucleotide polymorphisms (SNP) were generated. Distinct SNP signatures were identified through the combination of selection scans and association analyses. Phylogenetic analyses were also conducted, and we concluded that the Latifolium, Richmondi, and Marie-Galante race accessions were more genetically related to the G hirsutum cultivars and tend to cluster together. Fifty-four outlier SNP loci were identified by selection-scan analysis, and 3 SNPs were located in genes related to the processes of plant responding to stress conditions and confirmed through further genome-wide signals of marker-phenotype association analysis, which indicate a clear selection signature for such trait. These results identified useful candidate gene locus for cotton breeding programs.
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BACKGROUND: F-box proteins are substrate-recognition components of the Skp1-Rbx1-Cul1-F-box protein (SCF) ubiquitin ligases. By selectively targeting the key regulatory proteins or enzymes for ubiquitination and 26S proteasome mediated degradation, F-box proteins play diverse roles in plant growth/development and in the responses of plants to both environmental and endogenous signals. Studies of F-box proteins from the model plant Arabidopsis and from many additional plant species have demonstrated that they belong to a super gene family, and function across almost all aspects of the plant life cycle. However, systematic exploration of F-box family genes in the important fiber crop cotton (Gossypium hirsutum) has not been previously performed. The genome-wide analysis of the cotton F-box gene family is now possible thanks to the completion of several cotton genome sequencing projects. RESULTS: In current study, we first conducted a genome-wide investigation of cotton F-box family genes by reference to the published F-box protein sequences from other plant species. 592 F-box protein encoding genes were identified in the Gossypium hirsutume acc.TM-1 genome and, subsequently, we were able to present their gene structures, chromosomal locations, syntenic relationships with their parent species. In addition, duplication modes analysis showed that cotton F-box genes were distributed to 26 chromosomes, with the maximum number of genes being detected on chromosome 5. Although the WGD (whole-genome duplication) mode seems play a dominant role during cotton F-box gene expansion process, other duplication modes including TD (tandem duplication), PD (proximal duplication), and TRD (transposed duplication) also contribute significantly to the evolutionary expansion of cotton F-box genes. Collectively, these bioinformatic analysis suggest possible evolutionary forces underlying F-box gene diversification. Additionally, we also conducted analyses of gene ontology, and expression profiles in silico, allowing identification of F-box gene members potentially involved in hormone signal transduction. CONCLUSION: The results of this study provide first insights into the Gossypium hirsutum F-box gene family, which lays the foundation for future studies of functionality, particularly those involving F-box protein family members that play a role in hormone signal transduction.
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Proteínas F-Box/genética , Gossypium/genética , Proteínas de Plantas/genética , Proteínas F-Box/clasificación , Proteínas F-Box/metabolismo , Duplicación de Gen , Ontología de Genes , Genoma de Planta , Gossypium/metabolismo , Familia de Multigenes , Reguladores del Crecimiento de las Plantas/fisiología , Proteínas de Plantas/clasificación , Proteínas de Plantas/metabolismo , Proteínas Ligasas SKP Cullina F-box/fisiología , Transducción de SeñalRESUMEN
Abscission is a developmental process with important implications for agricultural practices. Ethylene has long been considered as a key regulator of the abscission process. The existence of an ethylene-independent abscission pathway, controlled by the complex of INFLORESCENCE DEFICIENT IN ABSCISSION (IDA) peptide and the HAESA (HAE) and HAESA-like2 (HSL2) kinases, has been proposed, based mainly on observations that organ abscission in ethylene-insensitive mutants was delayed but not inhibited. A recent review on plant organ abscission signaling highlighted the IDA-HAE-HSL2 components as the regulators of organ abscission, while the role of auxin and ethylene in this process was hardly addressed. After a careful analysis of the relevant abscission literature, we propose that the IDA-HAE-HSL2 pathway is essential for the final stages of organ abscission, while ethylene plays a major role in its initiation and progression. We discuss the view that the IDA-HAE-HSL2 pathway is ethylene independent, and present recent evidence showing that ethylene activates the IDA-HAE-HSL2 complex. We conclude that the ability of an organ to abscise is tightly linked to cell turgidity in the abscission zone, and suggest that lack of cell turgidity might contribute to the failure of floral organ abscission in the ida mutants.
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Etilenos/metabolismo , Flores/crecimiento & desarrollo , Desarrollo de la Planta , Plantas/metabolismo , Transducción de SeñalRESUMEN
OBJECTIVE: The aims of the study were to assess the overall reduction of pain in patients undergoing ultrasound-guided shoulder injections and to characterize the preinjection point-of-care ultrasound findings and use of clinical services postinjection including the use of magnetic resonance imaging and surgeries. DESIGN: Data of 172 patients who underwent ultrasound-guided subacromial subdeltoid injection or glenohumeral joint injection were reviewed for preinjection point-of-care ultrasound findings, change in pain intensity at 2 mos from baseline, and use of care at 6 mos' postinjection. Pain intensity was measured by the numeric rating scale and a dichotomous report of global impression of significant improvement in pain. Responders were defined as those with 50% or more reduction in numeric rating scale or those with global impression of 50% or more improvement. RESULTS: There were 141 responders among the 172 patients analyzed. Full-thickness rotator cuff tears were higher in the ultrasound-guided subacromial subdeltoid injection group when compared with the glenohumeral joint injection group (P = 0.038) and abnormal bicipital tendon findings higher in the glenohumeral joint injection group (P = 0.016). There were no significant differences in specific abnormal U findings between responders versus nonresponders. Twelve patients had a shoulder magnetic resonance imaging and four patients underwent operative interventions after the injection. CONCLUSIONS: Overall pain reduction after ultrasound-guided shoulder injections was favorable in the short term. There was no specific preinjection point-of-care ultrasound findings associated with clinical pain reduction after injection. Additional imaging and operative intervention after ultrasound-guided shoulder injections seemed to be relatively low.
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Sistemas de Atención de Punto , Articulación del Hombro/diagnóstico por imagen , Dolor de Hombro/tratamiento farmacológico , Ultrasonografía Intervencional , Anestésicos Locales/administración & dosificación , Femenino , Glucocorticoides/uso terapéutico , Humanos , Inyecciones Intraarticulares , Lidocaína/administración & dosificación , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Estudios Retrospectivos , Triamcinolona Acetonida/uso terapéuticoRESUMEN
In Arabidopsis, the F-box HAWAIIAN SKIRT (HWS) protein is important for organ growth. Loss of function of HWS exhibits pleiotropic phenotypes including sepal fusion. To dissect the HWS role, we EMS-mutagenized hws-1 seeds and screened for mutations that suppress hws-1 associated phenotypes. We identified shs-2 and shs-3 (suppressor of hws-2 and 3) mutants in which the sepal fusion phenotype of hws-1 was suppressed. shs-2 and shs-3 (renamed hst-23/hws-1 and hst-24/hws-1) carry transition mutations that result in premature terminations in the plant homolog of Exportin-5 HASTY (HST), known to be important in miRNA biogenesis, function and transport. Genetic crosses between hws-1 and mutant lines for genes in the miRNA pathway also suppress the phenotypes associated with HWS loss of function, corroborating epistatic relations between the miRNA pathway genes and HWS. In agreement with these data, accumulation of miRNA is modified in HWS loss or gain of function mutants. Our data propose HWS as a new player in the miRNA pathway, important for plant growth.
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Proteínas de Arabidopsis/genética , Arabidopsis/genética , Proteínas F-Box/genética , MicroARNs/genética , Arabidopsis/crecimiento & desarrollo , Proteínas de Arabidopsis/biosíntesis , Proteínas F-Box/biosíntesis , Regulación de la Expresión Génica de las Plantas , Mutación , Fenotipo , Plantas Modificadas Genéticamente/genética , Semillas/crecimiento & desarrollo , Transducción de SeñalRESUMEN
The Arabidopsis thaliana F-box gene HAWAIIAN SKIRT (HWS) affects organ growth and the timing of floral organ abscission. The loss-of-function hws-1 mutant exhibits fused sepals and increased organ size. To understand the molecular mechanisms of HWS during plant development, we mutagenized hws-1 seeds with ethylmethylsulphonate (EMS) and screened for mutations suppressing hws-1 associated phenotypes. We isolated the shs1/hws-1 (suppressor of hws-1) mutant in which hws-1 sepal fusion phenotype was suppressed. The shs1/hws-1 mutant carries a GâA nucleotide substitution in the MIR164 binding site of CUP-SHAPED COTYLEDON 1 (CUC1) mRNA. CUC1 and CUP-SHAPED COTYLEDON 2 (CUC2) transcript levels were altered in shs1, renamed cuc1-1D, and in hws-1 mutant. Genetic interaction analyses using single, double and triple mutants of cuc1-1D, cuc2-1D (a CUC2 mutant similar to cuc1-1D), and hws-1, demonstrate that HWS, CUC1 and CUC2 act together to control floral organ number. Loss of function of HWS is associated with larger petal size due to alterations in cell proliferation and mitotic growth, a role shared with the CUC1 gene.
Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/crecimiento & desarrollo , Proteínas F-Box/metabolismo , Flores/crecimiento & desarrollo , Arabidopsis/anatomía & histología , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Sitios de Unión , Proliferación Celular/fisiología , Tamaño de la Célula , Proteínas F-Box/genética , Retroalimentación Fisiológica/fisiología , Flores/anatomía & histología , Flores/genética , Flores/metabolismo , Regulación de la Expresión Génica de las Plantas , MicroARNs/metabolismo , Mutágenos , Mutación , Tamaño de los Órganos , Fenotipo , Plantas Modificadas Genéticamente , Unión Proteica , ARN Mensajero/metabolismo , Semillas/efectos de los fármacos , Semillas/genética , Semillas/crecimiento & desarrollo , Semillas/metabolismoRESUMEN
Plants can acclimate by using tropisms to link the direction of growth to environmental conditions. Hydrotropism allows roots to forage for water, a process known to depend on abscisic acid (ABA) but whose molecular and cellular basis remains unclear. Here we show that hydrotropism still occurs in roots after laser ablation removed the meristem and root cap. Additionally, targeted expression studies reveal that hydrotropism depends on the ABA signalling kinase SnRK2.2 and the hydrotropism-specific MIZ1, both acting specifically in elongation zone cortical cells. Conversely, hydrotropism, but not gravitropism, is inhibited by preventing differential cell-length increases in the cortex, but not in other cell types. We conclude that root tropic responses to gravity and water are driven by distinct tissue-based mechanisms. In addition, unlike its role in root gravitropism, the elongation zone performs a dual function during a hydrotropic response, both sensing a water potential gradient and subsequently undergoing differential growth.