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1.
Proc Natl Acad Sci U S A ; 121(13): e2309969121, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38498708

RESUMO

In this study, we model and predict rice yields by integrating molecular marker variation, varietal productivity, and climate, focusing on the Southern U.S. rice-growing region. This region spans the states of Arkansas, Louisiana, Texas, Mississippi, and Missouri and accounts for 85% of total U.S. rice production. By digitizing and combining four decades of county-level variety acreage data (1970 to 2015) with varietal information from genotyping-by-sequencing data, we estimate annual historical county-level allele frequencies. These allele frequencies are used together with county-level weather and yield data to develop ten machine learning models for yield prediction. A two-layer meta-learner ensemble model that combines all ten methods is externally evaluated against observations from historical Uniform Regional Rice Nursery trials (1980 to 2018) conducted in the same states. Finally, the ensemble model is used with forecasted weather from the Coupled Model Intercomparison Project across the 110 rice-growing counties to predict production in the coming decades for Composite Variety Groups assembled based on year of release, breeding program, and several breeding trends. Results indicate positive effects over time of public breeding on rice resilience to future climates, and potential reasons are discussed.


Assuntos
Oryza , Oryza/genética , Mudança Climática , Melhoramento Vegetal , Clima , Tempo (Meteorologia)
2.
Proc Natl Acad Sci U S A ; 120(4): e2207105120, 2023 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-36649409

RESUMO

Two species of rice have been independently domesticated from different ancestral wild species in Asia and Africa. Comparison of mutations that underlie phenotypic and physiological alterations associated with domestication traits in these species gives insights into the domestication history of rice in both regions. Asian cultivated rice, Oryza sativa, and African cultivated rice, Oryza glaberrima, have been modified and improved for common traits beneficial for humans, including erect plant architecture, nonshattering seeds, nonpigmented pericarp, and lack of awns. Independent mutations in orthologous genes associated with these traits have been documented in the two cultivated species. Contrary to this prevailing model, selection for awnlessness targeted different genes in O. sativa and O. glaberrima. We identify Regulator of Awn Elongation 3 (RAE3) a gene that encodes an E3 ubiquitin ligase and is responsible for the awnless phenotype only in O. glaberrima. A 48-bp deletion may disrupt the substrate recognition domain in RAE3 and diminish awn elongation. Sequencing analysis demonstrated low nucleotide diversity in a ~600-kb region around the derived rae3 allele on chromosome 6 in O. glaberrima compared with its wild progenitor. Identification of RAE3 sheds light on the molecular mechanism underlying awn development and provides an example of how selection on different genes can confer the same domestication phenotype in Asian and African rice.


Assuntos
Oryza , Humanos , Oryza/genética , Domesticação , Ubiquitina-Proteína Ligases/genética , Mutação , Sementes/genética
3.
Ophthalmic Plast Reconstr Surg ; 40(2): 212-216, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37972974

RESUMO

PURPOSE: This study aims to compare the readability of patient education materials (PEM) of the American Society of Ophthalmic Plastic and Reconstructive Surgery to that of PEMs generated by the AI-chat bots ChatGPT and Google Bard. METHODS: PEMs on 16 common American Society of Ophthalmic Plastic and Reconstructive Surgery topics were generated by 2 AI models, ChatGPT 4.0 and Google Bard, with and without a 6th-grade reading level prompt modifier. The PEMs were analyzed using 7 readability metrics: Flesch Reading Ease Score, Gunning Fog Index, Flesch-Kincaid Grade Level, Coleman-Liau Index, Simple Measure of Gobbledygook Index Score, Automated Readability Index, and Linsear Write Readability Score. Each AI-generated PEM was compared with the equivalent American Society of Ophthalmic Plastic and Reconstructive Surgery PEM. RESULTS: Across all readability indices, PEM generated by ChatGPT 4.0 consistently had the highest readability scores, indicating that the material generated by this AI chatbot may be most difficult to read in its unprompted form (Flesch Reading Ease Score: 36.5; Simple Measure of Gobbledygook: 14.7). Google's Bard was able to generate content that was easier to read than both the American Society of Ophthalmic Plastic and Reconstructive Surgery and ChatGPT 4.0 (Flesch Reading Ease Score: 52.3; Simple Measure of Gobbledygook: 12.7). When prompted to produce PEM at a 6th-grade reading level, both ChatGPT 4.0 and Bard were able to significantly improve in their readability scores, with prompted ChatGPT 4.0 being able to consistently generate content that was easier to read (Flesch Reading Ease Score: 67.9, Simple Measure of Gobbledygook: 10.2). CONCLUSION: This study suggests that AI tools, when guided by appropriate prompts, can generate accessible and comprehensible PEMs in the field of ophthalmic plastic and reconstructive surgeries, balancing readability with the complexity of the necessary information.


Assuntos
Oftalmologia , Cirurgia Plástica , Humanos , Compreensão , Folhetos , Educação de Pacientes como Assunto
4.
Artigo em Inglês | MEDLINE | ID: mdl-38819161

RESUMO

PURPOSE: To describe the outcomes of acellular fish skin grafts for repair of periocular anterior lamella skin defects after Mohs surgery for skin cancers. METHODS: Following the institutional review board approval, we conducted a retrospective chart review of patients treated with acellular fish skin grafts between January 2022 and December 2023. Indication was to repair defects after Mohs excision of basal cell carcinoma and squamous cell carcinoma. Demographics, smoking and diabetes status, diagnosis, defect location, graft size, and complications were evaluated. Outcomes were analyzed using the scar cosmesis assessment and rating scale. RESULTS: Six patients (3 females and 3 males) with a mean age of 60.8 (range 44-80) had Mohs surgery for basal cell carcinoma (4) and squamous cell carcinoma (2). Location of defects included eyebrow (3 cases), lateral nasal wall (1 case), lower eyelid (1 case), and medial lower eyelid/nasal wall (1 case). Defect size ranged from 8 × 10 mm to 30 × 40 mm. Two patients had more than 1 application of xenograft. One patient developed a mild cicatricial ectropion. No other postoperative complications were seen, and all had good wound healing and cosmetically acceptable results. CONCLUSIONS: In this pilot study, acellular fish skin xenografts are shown to be promising skin graft substitutes in patients with Mohs defects and decrease the need for autologous skin harvesting or allogenic skin donation.

5.
Ophthalmic Plast Reconstr Surg ; 39(2): 146-149, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36095843

RESUMO

PURPOSE: To compare postoperative infection (PI) rates using sterile and clean-boxed gloves in office-based oculoplastic procedures. METHODS: Prospective, comparative study of patients undergoing oculoplastic procedures by a single surgeon (RS) in an office-based procedure room between October 2018 and September 2020. Participants included were 18 years or older. Excluded were patients on oral antibiotics within 2 weeks before the procedure, had a follow-up period of less than 1 week, had a contaminated wound, had complex reconstructions, or had multiple simultaneous procedures performed. Oculoplastic procedures were performed using either sterile or clean-boxed gloves. The main outcome measure was the frequency of postoperative infection. RESULTS: Three thousand one hundred twenty-nine patients, 1,815 (58%) of whom were women, with a mean age of 60 (18-102) years were included. One thousand five hundred seventy procedures were performed with sterile gloves, while 1,559 were performed with clean-boxed gloves. The patients in the 2 groups were similar in age, gender, and number of high-risk individuals. One patient in the sterile glove group who underwent upper blepharoplasty (0.064%) and one patient (0.064%) in the clean-boxed glove group who had an external levator advancement blepharoptosis repair developed PI. Neither patient had risk factors for infection, and both infections resolved after 1 week of oral amoxicillin-clavulanate 875/125 mg twice daily. CONCLUSIONS: In minimally complex in-office oculoplastic procedures, using sterile versus clean-boxed gloves resulted in similar low infection rates in this large cohort. The healthcare benefits may not outweigh the costs of using sterile gloves universally for office-based oculoplastic procedures.


Assuntos
Blefaroplastia , Infecção da Ferida Cirúrgica , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Prospectivos , Esterilização , Luvas Cirúrgicas , Amoxicilina
6.
Orbit ; 42(4): 450-454, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35226576

RESUMO

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of lymphoma, involving the lumen of predominantly small blood vessels, especially capillaries. The orbit is an uncommon site of involvement for IVLBCL, and diagnosis before autopsy is even more rare as most cases are established post-mortem. Herein, the authors describe a 73-year-old male who presented with 3 weeks of progressive bilateral ptosis and ophthalmoplegia. Computed tomography (CT) and subsequent magnetic resonance imaging (MRI) revealed diffuse abnormal thickening and enhancement of bilateral orbital apices, superior orbital fissures, and cavernous sinus, along with persistent focal opacification of the left frontal and ethmoid sinuses. Infectious and inflammatory workup of serum and cerebrospinal fluid was negative. Ethmoidal sinus and middle turbinate biopsy confirmed intravascular large B-cell lymphoma and the patient was started on R-CHOP chemotherapy regimen.


Assuntos
Linfoma Difuso de Grandes Células B , Oftalmoplegia , Masculino , Humanos , Idoso , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Oftalmoplegia/diagnóstico , Oftalmoplegia/tratamento farmacológico , Oftalmoplegia/etiologia , Biópsia
7.
Plant Cell Environ ; 45(9): 2554-2572, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35735161

RESUMO

Plant function arises from a complex network of structural and physiological traits. Explicit representation of these traits, as well as their connections with other biophysical processes, is required to advance our understanding of plant-soil-climate interactions. We used the Terrestrial Regional Ecosystem Exchange Simulator (TREES) to evaluate physiological trait networks in maize. Net primary productivity (NPP) and grain yield were simulated across five contrasting climate scenarios. Simulations achieving high NPP and grain yield in high precipitation environments featured trait networks conferring high water use strategies: deep roots, high stomatal conductance at low water potential ("risky" stomatal regulation), high xylem hydraulic conductivity and high maximal leaf area index. In contrast, high NPP and grain yield was achieved in dry environments with low late-season precipitation via water conserving trait networks: deep roots, high embolism resistance and low stomatal conductance at low leaf water potential ("conservative" stomatal regulation). We suggest that our approach, which allows for the simultaneous evaluation of physiological traits, soil characteristics and their interactions (i.e., networks), has potential to improve our understanding of crop performance in different environments. In contrast, evaluating single traits in isolation of other coordinated traits does not appear to be an effective strategy for predicting plant performance.


Assuntos
Estômatos de Plantas , Água , Secas , Ecossistema , Grão Comestível , Folhas de Planta/fisiologia , Estômatos de Plantas/fisiologia , Solo/química , Água/fisiologia , Xilema/fisiologia
8.
Br J Clin Pharmacol ; 88(7): 3392-3403, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35236002

RESUMO

AIM: This phase I study investigated talazoparib pharmacokinetics (PK) and safety in patients with advanced solid tumours and varying degrees of hepatic function. METHODS: Patients with advanced solid tumours and normal hepatic function or varying degrees of hepatic impairment (mild, moderate or severe, based on National Cancer Institute Organ Dysfunction Working Group classification) received talazoparib 0.5 mg once daily for 22 calendar days. Plasma and urine samples after single and multiple doses were collected and analysed for talazoparib using validated assays. Plasma PK data from all patients were analysed using the population PK method. Plasma and urine PK parameters in PK-evaluable patients were calculated using noncompartmental analysis (NCA). Safety was monitored in all enrolled patients. RESULTS: Thirty-eight patients were enrolled; 37 had ≥1 PK concentration, among which 17 were evaluable for NCA. Population PK analysis (n = 37) indicated no significant impact of hepatic function on apparent clearance (CL/F) of talazoparib. Baseline creatinine clearance was the only significant covariate on CL/F (α = 0.05). NCA of data (n = 17) showed no clear trend for increase in exposure on day 22 with worsening hepatic function. Talazoparib protein binding was comparable in patients with varying hepatic function. Talazoparib was generally well tolerated, and the safety profile observed in this study was consistent with the known safety profile of the drug. CONCLUSIONS: Hepatic impairment (mild, moderate or severe) has no impact on the PK of talazoparib. No dose modification is recommended for patients with advanced solid tumours and various degrees of hepatic impairment, and this labelling language has been approved by the US Food and Drug Administration and the European Medicines Agency.


Assuntos
Hepatopatias , Neoplasias , Ftalazinas , Humanos , Hepatopatias/complicações , Hepatopatias/tratamento farmacológico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Ftalazinas/efeitos adversos , Ftalazinas/farmacocinética
9.
Ophthalmic Plast Reconstr Surg ; 38(6): 602-605, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36136735

RESUMO

PURPOSE: The authors report on a 10-year experience of correcting tarsal ectropion using a combined method of modified Bick eyelid tightening (MBLT) and inverting sutures. METHODS: Retrospective, interventional case series of consecutive patients with tarsal ectropion who underwent MBLT and inverting sutures by a single surgeon (RS) between July 2010 and July 2020. Thirty-four patients, 24 of whom were female, with a mean age of 81.6 years (range 59-92) were included. Eight patients had bilateral disease. All procedures were performed under local anesthesia in an office setting. Treatment success was defined by eyelid position, symptoms, and need for reoperation. RESULTS: Thirty-one patients (91%) had a successful outcome. Three patients (9%) had satisfactory results with improved symptoms and mild residual ectropion, for which further surgery was not required. No patients had poor results. The mean follow-up time was 4.5 months (range 3-11 months). The inverting sutures were well tolerated in all cases and none had to be removed due to ocular surface discomfort. There were no visible scars from the inverting sutures in any patient at postoperative month 3. CONCLUSIONS: A combination of eyelid tightening using MBLT and inverting sutures is a simple and effective treatment for lower eyelid tarsal ectropion with minimal tissue dissection.


Assuntos
Ectrópio , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Ectrópio/cirurgia , Estudos Retrospectivos , Técnicas de Sutura , Pálpebras/cirurgia , Suturas
10.
Ophthalmic Plast Reconstr Surg ; 38(4): e96-e99, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35093987

RESUMO

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is thought to be a precursor to mucinous carcinoma, both of which are rare. In this case report, the authors present a 55-year-old woman with concurrent EMPSGC and mucinous carcinoma manifesting with 2 distinct lesions on her left upper and lower eyelid and 1 lesion on her right lower eyelid. Biopsy and immunohistochemical staining supported primary cutaneous origin of the tumors. Systemic metastatic workup was initiated and thus far negative. The patient underwent staged slow Mohs micrographic surgery to remove one tumor at a time, with delayed reconstruction. This is the first reported case of EMPSGC and mucinous carcinoma presenting as distinct lesions both bilaterally and synchronously.


Assuntos
Adenocarcinoma de Células Claras , Adenocarcinoma Mucinoso , Neoplasias Palpebrais , Tumores Neuroendócrinos , Neoplasias das Glândulas Sudoríparas , Adenocarcinoma Mucinoso/cirurgia , Neoplasias Palpebrais/patologia , Pálpebras/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Mucinas , Neoplasias das Glândulas Sudoríparas/patologia , Glândulas Sudoríparas/patologia
11.
Semin Cell Dev Biol ; 90: 4-11, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30031214

RESUMO

The complex three-dimensional (3D) structure of the genome plays critical roles in the maintenance of genome stability, organization, and dynamics and in regulation of gene expression for understanding molecular mechanisms and diseases. Chromatin maintains biological functions and transcriptional activities through long distance interaction and interactions between loops and enhancers-promoters. We firstly overview the architecture and biology of chromatin and loops, topologically associated domains (TADs) and interactions, and compartments and functions. We specifically focus on CCCTC-binding factor (CTCF) in 3D genome organization and function to furthermore understand the significance of CTCF biology, transcriptional regulations, interactions with cohesin, roles in DNA binding, influences of CTCF degradation, and communication with wings-apart like (Wapl) protein. We also summarize the advanced single cell approaches to further monitor dynamics of CTCF functions and structures in the maintenance of 3D genome organization and function at single cell level.


Assuntos
Fator de Ligação a CCCTC/genética , Fator de Ligação a CCCTC/química , Fator de Ligação a CCCTC/metabolismo , Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/metabolismo , Cromatina/química , Cromatina/genética , Cromatina/metabolismo , Proteínas Cromossômicas não Histona/química , Proteínas Cromossômicas não Histona/metabolismo , Humanos , Coesinas
12.
Annu Rev Pharmacol Toxicol ; 58: 531-546, 2018 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-28977762

RESUMO

Lung cancer heterogeneity plays an important role in the development of drug resistance. Comprehensive molecular characterizations of lung cancer can describe hereditary and somatic gene changes, mutation, and heterogeneity. We discuss heterogeneity specificity, characterization, and roles of PIK3CD, TP53, and KRAS, as well as target-driven therapies and strategies applied in clinical trials based on a proposed precise self-validation system. The system is a specifically selected strategy of treatment for patients with cancer gene mutations and heterogeneity based on gene sequencing, following validation of the strategies in the patient's own cancer cells or in patient-derived xenografts using their own cancer cells isolated during surgery or biopsies. These results will be more precise if the drugs used in the strategies are selected through protein structure-guided compound screening or a DNA-encoded chemical library before validation in the patient's own cancer cells. Thus, a deeper understanding of heterogeneity mechanisms and improved validation of the therapeutic strategy will result in more precise treatments for patients.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Heterogeneidade Genética/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Animais , Ensaios Clínicos como Assunto , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Tratamento Farmacológico/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Mutação/genética
13.
Mod Pathol ; 34(8): 1456-1467, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33795830

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated clinical syndrome COVID-19 are causing overwhelming morbidity and mortality around the globe and disproportionately affected New York City between March and May 2020. Here, we report on the first 100 COVID-19-positive autopsies performed at the Mount Sinai Hospital in New York City. Autopsies revealed large pulmonary emboli in six cases. Diffuse alveolar damage was present in over 90% of cases. We also report microthrombi in multiple organ systems including the brain, as well as hemophagocytosis. We additionally provide electron microscopic evidence of the presence of the virus in our samples. Laboratory results of our COVID-19 cohort disclose elevated inflammatory markers, abnormal coagulation values, and elevated cytokines IL-6, IL-8, and TNFα. Our autopsy series of COVID-19-positive patients reveals that this disease, often conceptualized as a primarily respiratory viral illness, has widespread effects in the body including hypercoagulability, a hyperinflammatory state, and endothelial dysfunction. Targeting of these multisystemic pathways could lead to new treatment avenues as well as combination therapies against SARS-CoV-2 infection.


Assuntos
COVID-19/fisiopatologia , Pulmão/fisiopatologia , Embolia Pulmonar/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia , Coagulação Sanguínea , COVID-19/sangue , COVID-19/patologia , COVID-19/virologia , Causas de Morte , Citocinas/sangue , Feminino , Interações Hospedeiro-Patógeno , Humanos , Mediadores da Inflamação/sangue , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Embolia Pulmonar/sangue , Embolia Pulmonar/patologia , Embolia Pulmonar/virologia , SARS-CoV-2/patogenicidade
14.
New Phytol ; 232(4): 1765-1777, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34363228

RESUMO

Large structural variations frequently occur in higher plants; however, the impact of such variations on plant diversification, adaptation and domestication remains elusive. Here, we mapped and characterised a reciprocal chromosomal translocation in soybeans and assessed its effects on diversification and adaptation of wild (Glycine soja) and semiwild (Glycine gracilis) soybeans, and domestication of cultivated soybean (Glycine max), by tracing the distribution of the translocation in the USDA Soybean Germplasm Collection and population genetics analysis. We demonstrate that the translocation occurred through CACTA transposon-mediated chromosomal breakage in wild soybean c. 0.34 Ma and is responsible for semisterility in translocation heterozygotes and reduces their reproductive fitness. The translocation has differentiated Continental (i.e. China and Russia) populations from Maritime (i.e. Korea and Japan) populations of G. soja and predominately adapted to cold and dry climates. Further analysis revealed that the divergence of G. max from G. soja predates the translocation event and that G. gracilis is an evolutionary intermediate between G. soja and G. max. Our results highlight the effects of a chromosome rearrangement on the processes leading to plant divergence and adaptation, and provides evidence that suggests G. gracilis, rather than G. soja, as the ancestor of cultivated soybean.


Assuntos
Glycine max , Translocação Genética , Evolução Biológica , Domesticação , Genética Populacional , Glycine max/genética
15.
New Phytol ; 228(3): 898-909, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32557592

RESUMO

Understanding the genetic and physiological basis of abiotic stress tolerance under field conditions is key to varietal crop improvement in the face of climate variability. Here, we investigate dynamic physiological responses to water stress in silico and their relationships to genotypic variation in hydraulic traits of cotton (Gossypium hirsutum), an economically important species for renewable textile fiber production. In conjunction with an ecophysiological process-based model, heterogeneous data (plant hydraulic traits, spatially-distributed soil texture, soil water content and canopy temperature) were used to examine hydraulic characteristics of cotton, evaluate their consequences on whole plant performance under drought, and explore potential genotype × environment effects. Cotton was found to have R-shaped hydraulic vulnerability curves (VCs), which were consistent under drought stress initiated at flowering. Stem VCs, expressed as percent loss of conductivity, differed across genotypes, whereas root VCs did not. Simulation results demonstrated how plant physiological stress can depend on the interaction between soil properties and irrigation management, which in turn affect genotypic rankings of transpiration in a time-dependent manner. Our study shows how a process-based modeling framework can be used to link genotypic variation in hydraulic traits to differential acclimating behaviors under drought.


Assuntos
Secas , Gossypium , Aclimatação/genética , Genótipo , Gossypium/genética , Estresse Fisiológico/genética , Têxteis , Água
16.
New Phytol ; 225(2): 679-692, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31276231

RESUMO

Trees may survive prolonged droughts by shifting water uptake to reliable water sources, but it is unknown if the dominant mechanism involves activating existing roots or growing new roots during drought, or some combination of the two. To gain mechanistic insights on this unknown, a dynamic root-hydraulic modeling framework was developed that set up a feedback between hydraulic controls over carbon allocation and the role of root growth on soil-plant hydraulics. The new model was tested using a 5 yr drought/heat field experiment on an established piñon-juniper stand with root access to bedrock groundwater. Owing to the high carbon cost per unit root area, modeled trees initialized without adequate bedrock groundwater access experienced potentially lethal declines in water potential, while all of the experimental trees maintained nonlethal water potentials. Simulated trees were unable to grow roots rapidly enough to mediate the hydraulic stress, particularly during warm droughts. Alternatively, modeled trees initiated with root access to bedrock groundwater matched the hydraulics of the experimental trees by increasing their water uptake from bedrock groundwater when soil layers dried out. Therefore, the modeling framework identified a critical mechanism for drought response that required trees to shift water uptake among existing roots rather than growing new roots.


Assuntos
Carbono/metabolismo , Secas , Modelos Biológicos , Raízes de Plantas/fisiologia , Traqueófitas/fisiologia , Água/fisiologia , Simulação por Computador , Água Subterrânea , Juniperus/fisiologia , Pinus/fisiologia , Raízes de Plantas/crescimento & desenvolvimento , Transpiração Vegetal/fisiologia , Fatores de Tempo
17.
J Exp Bot ; 71(14): 4188-4200, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32277700

RESUMO

Adoption of rice varieties that perform well under high iron-associated (HIA) stress environments can enhance rice production in West Africa. This study reports the genetic characterization of 323 rice accessions and breeding lines cultivated in West Africa using genotyping-by-sequencing and their phenotypic response to HIA treatments in hydroponic solution (1500 mg l-1 FeSO4·7H2O) and hot-spot fields. The germplasm consisted of four genetic subpopulations: Oryza glaberrima (14%), O. sativa-japonica (7%), O. sativa-indica Group 1 (45%), and O. sativa-indica Group 2 (25%). Severe versus mild stress in the field was associated with a reduced SPAD value (12%), biomass (56%), and grain yield (57%), with leaf bronzing explaining 30% and 21% of the variation for biomass and grain yield, respectively. Association mapping using 175 indica genotypes identified 23 significant single nucleotide polymorphism (SNP) markers that mapped to 14 genomic regions. Genome-wide association study (GWAS) signals associated with leaf bronzing, a routinely used indicator of HIA stress, differed in hydroponic compared with field conditions. Contrastingly, six significant SNPs on chromosomes 8 and 9 were associated with the SPAD value under HIA stress in both field and hydroponic experiments, and a candidate potassium transporter gene mapped under the peak on chromosome 8. This study helps define criteria for assessing rice performance under HIA environments.


Assuntos
Oryza , África Ocidental , Estudo de Associação Genômica Ampla , Ferro , Oryza/genética , Melhoramento Vegetal , Polimorfismo de Nucleotídeo Único
18.
J Neurooncol ; 146(2): 339-346, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31873875

RESUMO

PURPOSE: It can be challenging to differentiate pseudoprogression from progression. We assessed the ability of dynamic contrast enhanced T1 MRI (DCE-MRI) perfusion to identify pseudoprogression in melanoma brain metastases. METHODS: Patients with melanoma brain metastases who underwent immunotherapy and DCE-MRI were identified. Enhancing lesions ≥  5mm in diameter on DCE-MRI and that were new or increased in size between a week from beginning the treatment, and a month after completing the treatment were included in the analysis. The 90th percentiles of rVp and rKtrans and the presence or absence of hemorrhage were recorded. Histopathology served as the reference standard for pseudoprogression. If not available, pseudoprogression was defined as neurological and radiographic stability or improvement without any new treatment for ≥ 2 months. RESULTS: Forty-four patients were identified; 64% received ipilimumab monotherapy for a median duration of 9 weeks (range, 1-138). Sixty-four lesions in 44 patients were included in the study. Of these, nine lesions in eight patients were determined to be pseudoprogression and seven lesions were previously irradiated. Forty-four progression lesions and eight pseudoprogression lesions were hemorrhagic. Median lesion volume for pseudoprogression and progression were not significantly different, at 2.3 cm3 and 3.2 cm3, respectively (p = 0.82). The rVp90 was smaller in pseudoprogression versus progression, at 2.2 and 5.3, respectively (p = 0.02), and remained significant after false discovery rate adjustment (p = 0.04). CONCLUSIONS: Pseudoprogression exhibited significantly lower rVp90 on DCE-MRI compared with progression. This knowledge can be useful for managing growing lesions in patients with melanoma brain metastases who are receiving immunotherapy.


Assuntos
Neoplasias Encefálicas/patologia , Imunoterapia/métodos , Imageamento por Ressonância Magnética/métodos , Melanoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/terapia , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Melanoma/terapia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
19.
Br J Clin Pharmacol ; 86(4): 771-778, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31770456

RESUMO

AIMS: In vitro data show that talazoparib is a substrate for P-glycoprotein (P-gp) and breast cancer resistance protein transporters. This open-label, 2-arm, drug-drug interaction Phase 1 study in patients with advanced solid tumours assessed the effect of a P-gp inhibitor (itraconazole) and a P-gp inducer (rifampicin) on the pharmacokinetics of a single dose of talazoparib. The safety and tolerability of a single dose of talazoparib with and without itraconazole or rifampicin were also assessed. METHODS: Thirty-six patients were enrolled (Arm A [itraconazole], n = 19; Arm B [rifampicin], n = 17). Patients in both arms received 2 single oral doses of talazoparib (0.5 mg, Arm A; 1 mg, Arm B) alone and with multiple daily oral doses of itraconazole (Arm A) or rifampicin (Arm B). RESULTS: Coadministration of itraconazole and talazoparib increased talazoparib area under the plasma concentration-time profile from time 0 extrapolated to infinity by ~56% and maximum observed plasma concentration by ~40% relative to talazoparib alone. Coadministration of rifampicin and talazoparib increased talazoparib maximum observed plasma concentration by approximately 37% (geometric mean ratio 136.6% [90% confidence interval 103.2-180.9]); area under the curve was not affected relative to talazoparib alone (geometric mean ratio 102.0% [90% confidence interval 94.0-110.7]). Talazoparib had an overall safety profile consistent with that observed in prior studies in which talazoparib was administered as a single dose. CONCLUSION: Coadministration of itraconazole increased talazoparib plasma exposure compared to talazoparib alone. A reduced talazoparib dose is recommended if coadministration of potent P-gp inhibitors cannot be avoided. Similar exposure was observed when talazoparib was administered alone and with rifampicin suggesting that the effect of rifampicin on talazoparib exposure is limited.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Neoplasias , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Área Sob a Curva , Interações Medicamentosas , Humanos , Proteínas de Neoplasias , Ftalazinas
20.
Doc Ophthalmol ; 141(3): 293-305, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32542469

RESUMO

PURPOSE: The electroretinogram (ERG) has proven to be useful in the evaluation and monitoring of patients with posterior uveitis. ERG oscillatory potentials (OPs) are sometimes reduced in many uveitic eyes with otherwise grossly normal ERG responses. This study compares ERG parameters, including OPs, between patients with birdshot chorioretinopathy, other posterior uveitis, and controls. METHODS: This was a retrospective case-control study. Sixty-four patients seen at a clinical practice had a total of 93 visits during which ERG was performed on both eyes. ERG data from 93 age-matched controls were also collected. Root-mean-squared (RMS) energy of the OPs was calculated using Fourier analysis for 88 patients and 88 age-matched controls for whom complete data were available. Photopic flicker amplitudes, photopic flicker latencies, scotopic b-wave amplitudes, and OP RMS values were compared between patients and controls. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves. RESULTS: The mean ages of patients and controls were 55.9 ± 10.8 (SD) years and 55.1 ± 11.5, respectively. 83% of the patients had a diagnosis of BCR. The mean OP RMS value was significantly different in patients (15.6 µV ± 9.7 µV) versus control eyes (33.0 µV ± 12.7 µV), p < 0.001. Area under the ROC curves (AUROC) was 0.75 for photopic flicker amplitudes, 0.77 for photopic flicker latencies, 0.72 for scotopic b-wave amplitudes, and 0.88 for OP RMS. AUROC was significantly different between OP RMS and photopic flicker amplitudes (p < 0.001), between OP RMS and flicker latencies (p = 0.0032), and between OP RMS and scotopic b-wave amplitudes (p < 0.0001). CONCLUSION: Analysis of OPs shows greater sensitivity and specificity in the diagnosis and evaluation of patients with birdshot chorioretinopathy than photopic and scotopic ERG amplitudes and photopic flicker latencies.


Assuntos
Coriorretinopatia de Birdshot/fisiopatologia , Eletrorretinografia , Retina/fisiopatologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oscilometria , Estimulação Luminosa , Curva ROC , Estudos Retrospectivos , Uveíte Posterior/fisiopatologia , Acuidade Visual/fisiologia
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